Our study investigated whether the f amilial aggregation of glioma is due to environmental or genetic effects and it investigated and compared the risk to spouses and firs t-degree relatives(FDR)of patients with prima...Our study investigated whether the f amilial aggregation of glioma is due to environmental or genetic effects and it investigated and compared the risk to spouses and firs t-degree relatives(FDR)of patients with primary brain tumou rs(PBT)for developing both PBT and the risk for other types of cancer.Al l PBT patients identified in Sweden f rom 1958-97in The Swedish Cancer Reg istry(SCR)were linked to the nationwide Swedish Fam ily Database,including persons in S weden born from 1932-97.The cohorts of spouses and FDR were linked to the SCR to identify observed cases of PBT and other cancer.S tandardised incidence ratios(SIR)were calculated using the incidence rates from SCR as the reference.We found that there were no increased risks for any specific type of PBT in the cohort of spouses.In the FDR cohort,generally the risk for a PBT was significantly increased by 2to 3times for the same h istopathology as the probands.Spouses of PBT patients had an increased risk of skin cancer.We conclude that FDR,not spouses,have a significantly increased risk,which indicates a genetic origin of the familial aggrega tion of brain展开更多
The high Li-ion conductivity of the Li7P3S11 sulfide-based solid electrolyte makes it a promising candidate for all-solid-state lithium batteries. The Li-ion transport over electrode-electrolyte and electrolyteelectro...The high Li-ion conductivity of the Li7P3S11 sulfide-based solid electrolyte makes it a promising candidate for all-solid-state lithium batteries. The Li-ion transport over electrode-electrolyte and electrolyteelectrolyte interfaces, vital for the performance of solid-state batteries, is investigated by impedance spectroscopy and solid-state NMR experiments. An all-solid-state Li-ion battery is assembled with the Li7P3S11 electrolyte, nano-Li2S cathode and Li-In foil anode, showing a relatively large initial discharge capacity of 1139.5 m Ah/g at a current density of 0.064 m A/cm^ 2 retaining 850.0 m Ah/g after 30 cycles. Electrochemical impedance spectroscopy suggests that the decrease in capacity over cycling is due to the increased interfacial resistance between the electrode and the electrolyte. 1D exchange ^7Li NMR quantifies the interfacial Li-ion transport between the uncycled electrode and the electrolyte, resulting in a diffusion coefficient of 1.70(3) ×10^-14cm^2/s at 333 K and an energy barrier of 0.132 e V for the Li-ion transport between Li2S cathode and Li7P3S11 electrolyte. This indicates that the barrier for Li-ion transport over the electrode-electrolyte interface is small. However, the small diffusion coefficient for Li-ion diffusion between the Li2S and the Li7P3S11 suggests that these contact interfaces between electrode and electrolyte are relatively scarce, challenging the performance of these solid-state batteries.展开更多
Background: hTERT is a key player in telomere biology and its activity is directly related to cell senescence and development of many health-related problems including cancer. Although previous studies investigated th...Background: hTERT is a key player in telomere biology and its activity is directly related to cell senescence and development of many health-related problems including cancer. Although previous studies investigated this association, the results greatly vary among populations. This study aimed to investigate the association of hTERT gene SNPs and the risk of breast cancer (BC) in Egyptian females and their impact on telomere length (TL). Methods: 218 BC patients and 178 age-matched healthy females were genotyped for hTERT variants rs2736098G > A, rs2735940C > T using PCR-RFLP and for MNS16A tandem repeat using PCR to determine their association with breast cancer risk. Telomere length was measured using qPCR. Results: hTERT rs2736098G > A results indicated that both AG and GG genotypes and G allele were associated with an increased risk of BC. The rs2735940 TT genotype was significantly associated with BC risk, however, the MNS16A tandem repeat region polymorphism didn’t show any correlation with the risk of developing BC. TL showed a significant reduction in BC patients with age 40 years compared with controls. However, it didn’t show a significant difference above the age of 40 years. Conclusions: hTERT rs2736098 and rs27365940, not MNS16A may be associated with an increased risk of developing BC in Egyptian females. Also, telomere length can be a promising screening marker of BC especially in young population.展开更多
The periodontal ligament (PDL) contains oxytalan fibers as well as collagen fibers, which helps it to withstand the mechanical stress to which it is constantly exposed. The oxytalan fibers are produced by PDL fibrobla...The periodontal ligament (PDL) contains oxytalan fibers as well as collagen fibers, which helps it to withstand the mechanical stress to which it is constantly exposed. The oxytalan fibers are produced by PDL fibroblasts. However, the arrangement of PDL fibroblasts and the orientation of oxytalan fibers relative to the fibroblast cell axis have not been investigated under the condition of mechanical stress. We hypothesized that such stress would alter the arrangement and orientation of these cells and their oxytalan fibers. The aim of this study was to evaluate the effects of stretching strain on PDL fibroblasts, focusing on the cellular arrangement and orientation of oxytalan fibers relative to the long cell axis in cell/matrix layers by staining the major component of the fibers, fibrillin-1. The angle between the long cell axis and the oxytalan fibers was approximately 70 degrees under both non-stretching and stretching conditions. Moreover, stretching induced the rearrangement of the cells. This is the first study to demonstrate that stretching induces the rearrangement of the PDL fibroblasts without altering the angle between the long cell axis and the oxytalan fibers. These results may reflect the orientation of oxytalan fibers in the PDL under the condition of mechanical stress.展开更多
Walterinnesia aegyptia is one of the most venomous snakes belonging to the family Elapidae found in the Middle East and Africa. In addition to its ecological importance, it is accused of millions of deaths due to snak...Walterinnesia aegyptia is one of the most venomous snakes belonging to the family Elapidae found in the Middle East and Africa. In addition to its ecological importance, it is accused of millions of deaths due to snakebites. Because molecular identification of snakes is crucial for the antivenom drug industry, mitochondrial genes are used to identify, characterize, and infer genetic diversity among different venomous snake species. Data of Walterinnesia collected from samples across Saudi Arabia were compared based on the mitochondrial 16S and 12S rRNA sequences with other Elapidae related taxa to assess the phylogenetic relationship. The phylogenetic analysis strongly supports the monophyly of the genus Walterinnesia based on two genes that represent different species of Elapidae. In addition, a close relationship between Walterinnesia aegyptia and W. morgani was found. Our molecular data showed that W. morgani from Riyadh, Saudi Arabia, is nearly genetically identical (D = 0) with W. aegyptia from Ha’il and Riyadh, Saudi Arabia, and Sinai, Egypt. Further study is required based on more material and detailed morphological and genetic analysis.展开更多
Background: Hyperthermia (HT) in oncology was originally applied as a stand-alone treatment (monotherapy), but achieving temperatures required to cause cellular destruction (>43ºC) proved to be challenging...Background: Hyperthermia (HT) in oncology was originally applied as a stand-alone treatment (monotherapy), but achieving temperatures required to cause cellular destruction (>43ºC) proved to be challenging. Lower temperatures may increase the risk of dissemination of the treated tumours. Hyperthermia in the current context of oncology therefore aims to achieve moderate temperatures of 39ºC - 41.5ºC and is applied in combination with chemotherapy (ChT) and/or radiotherapy (RT). Modulated electro-hyperthermia (mEHT) applies amplitude modulation to an electric field generated by a capacitive coupled set-up, to selectively heat tumours. As mEHT does not appear to increase the risk of disease dissemination, it has been investigated as a stand-alone treatment for patients with advanced disease and who have exhausted all other treatment options. This report is a descriptive review of papers in oncology which report on the use of mEHT as a stand-alone treatment in a palliative setting. We aim to establish whether there is motivation for the development of trials to further investigate mEHT as a monotherapy in a palliative setting. Methods: A literature search was conducted using the key words “Oncothermia”, “modulated electro-hyperthermia” and “monotherapy”, and case reports were excluded. Only studies which applied mEHT without ChT or RT;for palliative intent;when conventional therapies have failed;or when no further options are available, were included. Results: Six phase I/II studies on tumours of the liver, brain, pancreas, and stomach were included. The studies demonstrated the safety of mEHT;disease stabilisation;and improved quality of life. Conclusion: mEHT may have a role in the palliative management of certain tumours in the absence of any other treatment options. The development of robustly designed studies on mEHT for palliative management of oncology patients is motivated.展开更多
Background: Few previous studies have described other than age- and gender related changes in regional cerebral blood flow (rCBF) in healthy elderly. What is the influence of other common clinically relevant variables...Background: Few previous studies have described other than age- and gender related changes in regional cerebral blood flow (rCBF) in healthy elderly. What is the influence of other common clinically relevant variables such as ache, education, MMSE, and smoking history? Purpose: To study rCBF in Swedish healthy elderly by single-photon emission computed tomography (SPECT) and evaluate the influence on rCBF of age, gender, education, MMSE, ache, and smoking with a focus on education in relation to the ‘cognitive reserve’. Methods: Healthy subjects (n = 45, 50 -75 y), sampled from a large longitudinal aging study took part in an extensive examination of health and memory, including cognitive testing and socio-economic survey. After injection of 99 mTc-hexamethylpropylene amine oxime (HMPAO) followed by SPECT the rCBF-SPECT images were analyzed using statistical parametric mapping (SPM). Results: Age-related decreases in uptake were seen in interhemispheric and interlobar regions. There was a positive rCBF correlation with education in the inferior frontal lobe and a higher uptake in the left temporal lobe in an age-gender-matched high education subgroup. Conclusion: The localization of the age related findings except for the medial temporal lobe differs markedly from typical dementia related findings. A reduction close to interhemispheric or interlobar space should always be related to chronological age. Education seems to have an influence on basal brain function at a resting-state condition. Knowledge of normal rCBF variations for variables such as age and education should be considered when making clinical diagnosis. The findings could be interpreted as further support for the theory of cognitive reserve.展开更多
Concomitant fields are the unwanted transverse components that arise when spatial encoding gradients are applied in MRI.We measured the changing gradient magnetic field at multiple locations inside the scanner and exa...Concomitant fields are the unwanted transverse components that arise when spatial encoding gradients are applied in MRI.We measured the changing gradient magnetic field at multiple locations inside the scanner and examined the internal distribution and linearity of the three vector components of the field.Our results illustrate some not-so-obvious spatial characteristics of the gradient field,which can seem unintuitive at first glance,but are quite reasonable when considering electromagnetic theory and MRI-scanner physics constraints.展开更多
Background: Prostate cancer (PCa) is the most common form of cancer among males in Europe and in the USA and the most common curative treatment is removal of the prostate, i.e. prostatectomy. After the removal, the pr...Background: Prostate cancer (PCa) is the most common form of cancer among males in Europe and in the USA and the most common curative treatment is removal of the prostate, i.e. prostatectomy. After the removal, the prostate is histopathologically analysed. One area of interest is to examine the perifery of the prostate, as tumours on and near the surface can indicate that the PCa has spread to other parts of the body. There are no current methods to examine the surface of the prostate at the time of surgery. Tactile resonance sensors can be used for detecting areas of different stiffness in soft tissue. Human prostate tissue affected by cancer is usually stiffer than healthy tissue, and for this purpose, a tactile resonance sensor was developed. The aim of this study was to investigate the depth at which embedded stiffer volumes could be detected, using soft tissue phantoms. Methods: With the tactile resonance sensor used in this study, the shift of the resonance frequency and the force at contact with tissue can be measured, and combined into a tissue stiffness parameter. The detection sensitivity of the sensor at impression depths, 0.4 and 0.8 mm, was measured for detection of inserted nodules of stiff silicone in softer silicone and in chicken muscle tissue, mimicking prostate tissue with cancer tumours. Results: Measurements on the silicone samples detected the hidden stiffer object at a depth of 1 - 4 mm with a difference in the stiffness parameter of 80 - 900 mN/kHz (p < 0.028, n = 48). At the depth 5 - 6 mm the difference was smaller but still significant < 30 mN/kHz (p < 0.05, n = 24). For the measurements on chicken muscle, the detectable depth was 4 mm (p < 0.05, n = 24). Conclusion: This model study suggests that, with only a small impression depth of ≤1 mm, the resonance sensor system described here can detect stiffness variations located at least 4 mm in silicone and chicken muscle, mimicking tumours in prostate tissue.展开更多
The use of hyperthermia as a treatment in oncology is a common topic for debate. Some researchers expect a breakthrough in oncological treatments with hyperthermia, whereas others have disregarded the method. Serious ...The use of hyperthermia as a treatment in oncology is a common topic for debate. Some researchers expect a breakthrough in oncological treatments with hyperthermia, whereas others have disregarded the method. Serious questions concerning hyperthermia have arisen. Should homogeneous (isothermal) or heterogeneous (selective) heating being used? When we use selective heating (heterogeneity), should the entire tumour be targeted or should the malignant cells be individually selected? Does the mechanism involve thermal cell death or thermally-assisted cell death? Is the goal necrosis or apoptosis? Is hyperthermia safe as a monotherapy or does it have to be combined with conventional treatments? When the selection is local, how do we act on disseminated cells that represent a high risk of life threatening metastases? When local heating is the focus, how should it be carried out with measured and controlled? Our objective is to show how precise, selective heat transfer is necessary to remove malignant cells and, consequently, how hyperthermia as part of the immune-oncology can change the game in this promising field of oncological therapies.展开更多
Objectives: The aim of this study was to assess the levels of Y-box binding protein 1 (YBX-1) and interleukin 6 (IL-6) in the sera of metastatic and non-metastatic breast cancer patients (BC), investigate their clinic...Objectives: The aim of this study was to assess the levels of Y-box binding protein 1 (YBX-1) and interleukin 6 (IL-6) in the sera of metastatic and non-metastatic breast cancer patients (BC), investigate their clinicopathological significance and to analyze their potential use as biomarkers of breast cancer metastasis. Methods: The study included ninety subjects sub-grouped equally into metastatic BC, non-metastatic BC and healthy volunteers. Serum YBX-1 and IL-6 were quantified using ELISA technique while CA 15-3 was quantified using IRMA kit. Clinical data were collected from patients’ records. Results: YBX-1 (p < 0.001), IL-6 (p < 0.001) and CA15-3 (p = 0.017, 0.001) were significantly elevated in metastatic and non-metastatic BC patients compared to healthy controls, however, only YBX-1 (p 0.001) showed a significant difference with cancer metastasis. Generally, YBX-1 and IL-6 were correlated with worse histological grade and late clinical stage in breast cancer patients and they were also associated with axillary lymph nodes involvement and positive vascular invasion in metastatic BC patients. Serum YBX-1 and IL-6 levels were positively correlated to each other (rs = 0.615, p < 0.001) and they showed high sensitivity and specificity compared to CA 15-3 (p < 0.001 and p = 0.004 for YBX-1 and IL-6 respectively) for predicting cancer metastasis. Conclusions: Serum YBX-1 and IL-6 are potential biomarkers of breast cancer patients with significant correlation with bad clinicopathological characteristics. Serum YBX-1 and IL-6 have superior sensitivity and specificity compared to CA15-3 and can serve as potential follow up and prognostic markers.展开更多
Cancer patients frequently report a set of symptoms including fatigue, pain, and physiological and social distress. Families and other personal lay relations give proposals to take supportive drugs and supplemental nu...Cancer patients frequently report a set of symptoms including fatigue, pain, and physiological and social distress. Families and other personal lay relations give proposals to take supportive drugs and supplemental nutrients, without professional knowledge about their actions. Internet search engines and social networks serve up most of the treatment proposals, opening wide possibilities for quackeries and predatory money-making practices. Medical professionals have a responsibility to clear this field and concentrate on patients’ well-being and personal needs. According to our approach, the integration of supportive and palliative care with conventional therapies needs a change of paradigm from tumour-driven to patient-driven treatment actions. Supportive/palliative care includes a broad spectrum of applied methods, including medications, nourishments, electrical effects, and psycho and social supports. Our goal is to discuss the possibilities for combining conventional oncotherapies with additional supportive/palliative care and to give suggestions on a professional basis.展开更多
The controlled release of drugs using local ionizing radiation presents a promising approach for targeted cancer treatment,particularly when applied in concurrent radio-chemotherapy.In these approaches,radiation-gener...The controlled release of drugs using local ionizing radiation presents a promising approach for targeted cancer treatment,particularly when applied in concurrent radio-chemotherapy.In these approaches,radiation-generated reactive species often play an important role.However,the reactive species that can be used to trigger release have low yield and lack selectivity.Here,we demonstrate the generation of highly oxidative species when aqueous solutions containing low concentrations of organochlorides(such as chloroform)are irradiated with ionizing radiation at therapeutically relevant doses.These reactive species were identified as peroxyl radicals,which formed in a reaction cascade between organochlorides and aqueous electrons.We employed stilbene-based probes to investigate the oxidation process,showing double bond oxidation and cleavage.To translate this reactivity into a radiation-sensitive material,we synthesized a micelle-forming amphiphilic block copolymer that has stilbene as the linker between two blocks.Upon exposure to ionizing radiation,the oxidation of stilbene led to the cleavage of the polymer,which induces the dissociation of the block-copolymer micelles and the release of loaded drugs.展开更多
（MnFe）2（P, Si）-type compounds are, to date, one of the best candidates for magnetic refrigeration and energy conversion applications due to the combination of giant magnetocaloric effect （MCE）, tunable working t...（MnFe）2（P, Si）-type compounds are, to date, one of the best candidates for magnetic refrigeration and energy conversion applications due to the combination of giant magnetocaloric effect （MCE）, tunable working temperature range and low material cost. The giant MCE in the （Mn, Fe）2（P, Si）-type compounds originates from strong mag- netoelastic coupling, where the lattice degrees of freedom and spin degrees of freedom are efficiently coupled. The tunability of the phase transition, in terms of the critical temperature and the character of the phase transition, is essentially attributed to the changes in the magnetoelastic coupling in the （Mn, Fe）2（P, Si）-type compounds. In this review, not only the fundamentals of the magnetoelastic coupling but also the related practical aspects such as magnetocaloric performance, hysteresis issue and mechanical stability are discussed for the （Mn, Fe）2（P, Si）- type compounds. Additionally, some future fundamental studies on the MCE as well as possible ways of solving the hysteresis and fracture issues are proposed.展开更多
Magnetocaloric materials undergoing reversible phase transitions are highly desirable for magnetic refrigeration applications.(Mn,Fe)_(2)(P,Si)alloys exhibit a giant magnetocaloric effect accompanied by a magnetoelast...Magnetocaloric materials undergoing reversible phase transitions are highly desirable for magnetic refrigeration applications.(Mn,Fe)_(2)(P,Si)alloys exhibit a giant magnetocaloric effect accompanied by a magnetoelastic transition,while the noticeable irreversibility causes drastic degradation of the magnetocaloric properties during consecutive cooling cycles.In the present work,we performed a comprehensive study on the magnetoelastic transition of the(Mn,Fe)_(2)(P,Si)alloys by high-resolution transmission electron microscopy,in situ field-and temperature-dependent neutron powder diffraction as well as density functional theory calculations(DFT).We found a generalized relationship between the thermal hysteresis and the transition-induced elastic strain energy for the(Mn,Fe)_(2)(P,Si)family.The thermal hysteresis was greatly reduced from 11 to 1 K by a mere 4 at.%substitution of Fe by Mo in the Mn_(1.15)Fe_(0.80)P_(0.45)Si_(0.55)alloy.This reduction is found to be due to a strong reduction in the transition-induced elastic strain energy.The significantly enhanced reversibility of the magnetoelastic transition leads to a remarkable improvement of the reversible magnetocaloric properties,compared to the parent alloy.Based on the DFT calculations and the neutron diffraction experiments,we also elucidated the underlying mechanism of the tunable transition temperature for the(Mn,Fe)_(2)(P,Si)family,which can essentially be attributed to the strong competition between the covalent bonding and the ferromagnetic exchange coupling.The present work provides not only a new strategy to improve the reversibility of a first-order magnetic transition but also essential insight into the electron-spin-lattice coupling in giant magnetocaloric materials.展开更多
A novel protocol for the synthesis of perylene diimides(PDIs),by reacting perylene dianhydride(PDA)with aliphatic amines is reported.Full conversions were obtained at temperatures between 20 and 60℃,using DBU as the ...A novel protocol for the synthesis of perylene diimides(PDIs),by reacting perylene dianhydride(PDA)with aliphatic amines is reported.Full conversions were obtained at temperatures between 20 and 60℃,using DBU as the base in DMF or DMSO.A“green”synthesis of PDIs,that runs at higher temperatures,was developed using K_(2)CO_(3) in DMSO.展开更多
Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integr...Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.展开更多
Phase separation during the lithiation of redox-active materials is a critical factor affecting battery performance,including energy density,charging rates,and cycle life.Accurate physical descriptions of these materi...Phase separation during the lithiation of redox-active materials is a critical factor affecting battery performance,including energy density,charging rates,and cycle life.Accurate physical descriptions of these materials are necessary for understanding underlying lithiation mechanisms,performance limitations,and optimizing energy storage devices.This work presents an extended regular solution model that captures mutual interactions between sublattices of multi-sublattice battery materials,typically synthesized by metal substitution.We apply the model to phospho-olivine materials and demonstrate its quantitative accuracy in predicting the composition-dependent redox shift of the plateaus of LiMn_(y)Fe_(1-y)PO_(4)(LFMP),LiCo_(y)Fe_(1-y)PO_(4)(LFCP),LiCo_(x)Mn_(y)Fe_(1-y)PO_(4)(LFMCP),as well as their phase separation behavior.Furthermore,we develop a phase-field model of LFMP that consistently matches experimental data and identifies LiMn0.4Fe0.6PO4 as a superior composition that favors a solid solution phase transition,making it ideal for high-power applications.展开更多
Background:More than 25%of patients with solid cancers develop intracerebral metastases.Aside of surgery,radia-tion therapy(RT)is a mainstay in the treatment of intracerebral metastases.Postoperative fractionated ster...Background:More than 25%of patients with solid cancers develop intracerebral metastases.Aside of surgery,radia-tion therapy(RT)is a mainstay in the treatment of intracerebral metastases.Postoperative fractionated stereotactic RT(FSRT)to the resection cavity of intracerebral metastases is a treatment of choice to reduce the risk of local recur-rence.However,FSRT has to be delayed until a sufficient wound healing is attained;hence systemic therapy might be postponed.Neoadjuvant stereotactic radiosurgery(SRS)might offer advantages over adjuvant FSRT in terms of better target delineation and an earlier start of systemic chemotherapy.Here,we conducted a study to find the maximum tolerated dose(MTD)of neoadjuvant SRS for intracerebral metastases.Methods:This is a single-center,phase I dose escalation study on neoadjuvant SRS for intracerebral metastases that will be conducted at the Klinikum rechts der Isar Hospital,Technical University of Munich.The rule-based traditional 3+3 design for this trial with 3 dose levels and 4 different cohorts depending on lesion size will be applied.The primary endpoint is the MTD for which no dose-limiting toxicities(DLT)occur.The adverse events of each participant will be evaluated according to the Common Terminology Criteria for Adverse Events(CTCAE)version 5.0 continuously during the study until the first follow-up visit(4-6 weeks after surgery).Secondary endpoints include local control rate,survival,immunological tumor characteristics,quality of life(QoL),CTCAE grade of late clinical,neurological,and neurocognitive toxicities.In addition to the intracerebral metastasis which is treated with neoadjuvant SRS and resection up to four additional intracerebral metastases can be treated with definitive SRS.Depending on the occurrence of DLT up to 72 patients will be enrolled.The recruitment phase will last for 24 months.Discussion:Neoadjuvant SRS for intracerebral metastases offers potential advantages over postoperative SRS to the resection cavity,such as better target volume definition with subsequent higher efficiency of eliminating tumor cells,and lower damage to surrounding healthy tissue,and much-needed systemic chemotherapy could be initiated more rapidly.展开更多
文摘Our study investigated whether the f amilial aggregation of glioma is due to environmental or genetic effects and it investigated and compared the risk to spouses and firs t-degree relatives(FDR)of patients with primary brain tumou rs(PBT)for developing both PBT and the risk for other types of cancer.Al l PBT patients identified in Sweden f rom 1958-97in The Swedish Cancer Reg istry(SCR)were linked to the nationwide Swedish Fam ily Database,including persons in S weden born from 1932-97.The cohorts of spouses and FDR were linked to the SCR to identify observed cases of PBT and other cancer.S tandardised incidence ratios(SIR)were calculated using the incidence rates from SCR as the reference.We found that there were no increased risks for any specific type of PBT in the cohort of spouses.In the FDR cohort,generally the risk for a PBT was significantly increased by 2to 3times for the same h istopathology as the probands.Spouses of PBT patients had an increased risk of skin cancer.We conclude that FDR,not spouses,have a significantly increased risk,which indicates a genetic origin of the familial aggrega tion of brain
基金funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement no.[307161] of M.W.
文摘The high Li-ion conductivity of the Li7P3S11 sulfide-based solid electrolyte makes it a promising candidate for all-solid-state lithium batteries. The Li-ion transport over electrode-electrolyte and electrolyteelectrolyte interfaces, vital for the performance of solid-state batteries, is investigated by impedance spectroscopy and solid-state NMR experiments. An all-solid-state Li-ion battery is assembled with the Li7P3S11 electrolyte, nano-Li2S cathode and Li-In foil anode, showing a relatively large initial discharge capacity of 1139.5 m Ah/g at a current density of 0.064 m A/cm^ 2 retaining 850.0 m Ah/g after 30 cycles. Electrochemical impedance spectroscopy suggests that the decrease in capacity over cycling is due to the increased interfacial resistance between the electrode and the electrolyte. 1D exchange ^7Li NMR quantifies the interfacial Li-ion transport between the uncycled electrode and the electrolyte, resulting in a diffusion coefficient of 1.70(3) ×10^-14cm^2/s at 333 K and an energy barrier of 0.132 e V for the Li-ion transport between Li2S cathode and Li7P3S11 electrolyte. This indicates that the barrier for Li-ion transport over the electrode-electrolyte interface is small. However, the small diffusion coefficient for Li-ion diffusion between the Li2S and the Li7P3S11 suggests that these contact interfaces between electrode and electrolyte are relatively scarce, challenging the performance of these solid-state batteries.
文摘Background: hTERT is a key player in telomere biology and its activity is directly related to cell senescence and development of many health-related problems including cancer. Although previous studies investigated this association, the results greatly vary among populations. This study aimed to investigate the association of hTERT gene SNPs and the risk of breast cancer (BC) in Egyptian females and their impact on telomere length (TL). Methods: 218 BC patients and 178 age-matched healthy females were genotyped for hTERT variants rs2736098G > A, rs2735940C > T using PCR-RFLP and for MNS16A tandem repeat using PCR to determine their association with breast cancer risk. Telomere length was measured using qPCR. Results: hTERT rs2736098G > A results indicated that both AG and GG genotypes and G allele were associated with an increased risk of BC. The rs2735940 TT genotype was significantly associated with BC risk, however, the MNS16A tandem repeat region polymorphism didn’t show any correlation with the risk of developing BC. TL showed a significant reduction in BC patients with age 40 years compared with controls. However, it didn’t show a significant difference above the age of 40 years. Conclusions: hTERT rs2736098 and rs27365940, not MNS16A may be associated with an increased risk of developing BC in Egyptian females. Also, telomere length can be a promising screening marker of BC especially in young population.
文摘The periodontal ligament (PDL) contains oxytalan fibers as well as collagen fibers, which helps it to withstand the mechanical stress to which it is constantly exposed. The oxytalan fibers are produced by PDL fibroblasts. However, the arrangement of PDL fibroblasts and the orientation of oxytalan fibers relative to the fibroblast cell axis have not been investigated under the condition of mechanical stress. We hypothesized that such stress would alter the arrangement and orientation of these cells and their oxytalan fibers. The aim of this study was to evaluate the effects of stretching strain on PDL fibroblasts, focusing on the cellular arrangement and orientation of oxytalan fibers relative to the long cell axis in cell/matrix layers by staining the major component of the fibers, fibrillin-1. The angle between the long cell axis and the oxytalan fibers was approximately 70 degrees under both non-stretching and stretching conditions. Moreover, stretching induced the rearrangement of the cells. This is the first study to demonstrate that stretching induces the rearrangement of the PDL fibroblasts without altering the angle between the long cell axis and the oxytalan fibers. These results may reflect the orientation of oxytalan fibers in the PDL under the condition of mechanical stress.
文摘Walterinnesia aegyptia is one of the most venomous snakes belonging to the family Elapidae found in the Middle East and Africa. In addition to its ecological importance, it is accused of millions of deaths due to snakebites. Because molecular identification of snakes is crucial for the antivenom drug industry, mitochondrial genes are used to identify, characterize, and infer genetic diversity among different venomous snake species. Data of Walterinnesia collected from samples across Saudi Arabia were compared based on the mitochondrial 16S and 12S rRNA sequences with other Elapidae related taxa to assess the phylogenetic relationship. The phylogenetic analysis strongly supports the monophyly of the genus Walterinnesia based on two genes that represent different species of Elapidae. In addition, a close relationship between Walterinnesia aegyptia and W. morgani was found. Our molecular data showed that W. morgani from Riyadh, Saudi Arabia, is nearly genetically identical (D = 0) with W. aegyptia from Ha’il and Riyadh, Saudi Arabia, and Sinai, Egypt. Further study is required based on more material and detailed morphological and genetic analysis.
文摘Background: Hyperthermia (HT) in oncology was originally applied as a stand-alone treatment (monotherapy), but achieving temperatures required to cause cellular destruction (>43ºC) proved to be challenging. Lower temperatures may increase the risk of dissemination of the treated tumours. Hyperthermia in the current context of oncology therefore aims to achieve moderate temperatures of 39ºC - 41.5ºC and is applied in combination with chemotherapy (ChT) and/or radiotherapy (RT). Modulated electro-hyperthermia (mEHT) applies amplitude modulation to an electric field generated by a capacitive coupled set-up, to selectively heat tumours. As mEHT does not appear to increase the risk of disease dissemination, it has been investigated as a stand-alone treatment for patients with advanced disease and who have exhausted all other treatment options. This report is a descriptive review of papers in oncology which report on the use of mEHT as a stand-alone treatment in a palliative setting. We aim to establish whether there is motivation for the development of trials to further investigate mEHT as a monotherapy in a palliative setting. Methods: A literature search was conducted using the key words “Oncothermia”, “modulated electro-hyperthermia” and “monotherapy”, and case reports were excluded. Only studies which applied mEHT without ChT or RT;for palliative intent;when conventional therapies have failed;or when no further options are available, were included. Results: Six phase I/II studies on tumours of the liver, brain, pancreas, and stomach were included. The studies demonstrated the safety of mEHT;disease stabilisation;and improved quality of life. Conclusion: mEHT may have a role in the palliative management of certain tumours in the absence of any other treatment options. The development of robustly designed studies on mEHT for palliative management of oncology patients is motivated.
基金Financial support was provided by Lion’s Cancer Research Foundation in Northern Sweden,the Swedish Knowledge Foundation,the Faculty of Medicine at Umea University,the Swedish research council and Borger-skapet in Umea research foundation.
文摘Background: Few previous studies have described other than age- and gender related changes in regional cerebral blood flow (rCBF) in healthy elderly. What is the influence of other common clinically relevant variables such as ache, education, MMSE, and smoking history? Purpose: To study rCBF in Swedish healthy elderly by single-photon emission computed tomography (SPECT) and evaluate the influence on rCBF of age, gender, education, MMSE, ache, and smoking with a focus on education in relation to the ‘cognitive reserve’. Methods: Healthy subjects (n = 45, 50 -75 y), sampled from a large longitudinal aging study took part in an extensive examination of health and memory, including cognitive testing and socio-economic survey. After injection of 99 mTc-hexamethylpropylene amine oxime (HMPAO) followed by SPECT the rCBF-SPECT images were analyzed using statistical parametric mapping (SPM). Results: Age-related decreases in uptake were seen in interhemispheric and interlobar regions. There was a positive rCBF correlation with education in the inferior frontal lobe and a higher uptake in the left temporal lobe in an age-gender-matched high education subgroup. Conclusion: The localization of the age related findings except for the medial temporal lobe differs markedly from typical dementia related findings. A reduction close to interhemispheric or interlobar space should always be related to chronological age. Education seems to have an influence on basal brain function at a resting-state condition. Knowledge of normal rCBF variations for variables such as age and education should be considered when making clinical diagnosis. The findings could be interpreted as further support for the theory of cognitive reserve.
文摘Concomitant fields are the unwanted transverse components that arise when spatial encoding gradients are applied in MRI.We measured the changing gradient magnetic field at multiple locations inside the scanner and examined the internal distribution and linearity of the three vector components of the field.Our results illustrate some not-so-obvious spatial characteristics of the gradient field,which can seem unintuitive at first glance,but are quite reasonable when considering electromagnetic theory and MRI-scanner physics constraints.
基金supported by The Industrial Doctoral School at Umea University and by grants from Objective 2 North Sweden-EU Structural Fund.
文摘Background: Prostate cancer (PCa) is the most common form of cancer among males in Europe and in the USA and the most common curative treatment is removal of the prostate, i.e. prostatectomy. After the removal, the prostate is histopathologically analysed. One area of interest is to examine the perifery of the prostate, as tumours on and near the surface can indicate that the PCa has spread to other parts of the body. There are no current methods to examine the surface of the prostate at the time of surgery. Tactile resonance sensors can be used for detecting areas of different stiffness in soft tissue. Human prostate tissue affected by cancer is usually stiffer than healthy tissue, and for this purpose, a tactile resonance sensor was developed. The aim of this study was to investigate the depth at which embedded stiffer volumes could be detected, using soft tissue phantoms. Methods: With the tactile resonance sensor used in this study, the shift of the resonance frequency and the force at contact with tissue can be measured, and combined into a tissue stiffness parameter. The detection sensitivity of the sensor at impression depths, 0.4 and 0.8 mm, was measured for detection of inserted nodules of stiff silicone in softer silicone and in chicken muscle tissue, mimicking prostate tissue with cancer tumours. Results: Measurements on the silicone samples detected the hidden stiffer object at a depth of 1 - 4 mm with a difference in the stiffness parameter of 80 - 900 mN/kHz (p < 0.028, n = 48). At the depth 5 - 6 mm the difference was smaller but still significant < 30 mN/kHz (p < 0.05, n = 24). For the measurements on chicken muscle, the detectable depth was 4 mm (p < 0.05, n = 24). Conclusion: This model study suggests that, with only a small impression depth of ≤1 mm, the resonance sensor system described here can detect stiffness variations located at least 4 mm in silicone and chicken muscle, mimicking tumours in prostate tissue.
文摘The use of hyperthermia as a treatment in oncology is a common topic for debate. Some researchers expect a breakthrough in oncological treatments with hyperthermia, whereas others have disregarded the method. Serious questions concerning hyperthermia have arisen. Should homogeneous (isothermal) or heterogeneous (selective) heating being used? When we use selective heating (heterogeneity), should the entire tumour be targeted or should the malignant cells be individually selected? Does the mechanism involve thermal cell death or thermally-assisted cell death? Is the goal necrosis or apoptosis? Is hyperthermia safe as a monotherapy or does it have to be combined with conventional treatments? When the selection is local, how do we act on disseminated cells that represent a high risk of life threatening metastases? When local heating is the focus, how should it be carried out with measured and controlled? Our objective is to show how precise, selective heat transfer is necessary to remove malignant cells and, consequently, how hyperthermia as part of the immune-oncology can change the game in this promising field of oncological therapies.
文摘Objectives: The aim of this study was to assess the levels of Y-box binding protein 1 (YBX-1) and interleukin 6 (IL-6) in the sera of metastatic and non-metastatic breast cancer patients (BC), investigate their clinicopathological significance and to analyze their potential use as biomarkers of breast cancer metastasis. Methods: The study included ninety subjects sub-grouped equally into metastatic BC, non-metastatic BC and healthy volunteers. Serum YBX-1 and IL-6 were quantified using ELISA technique while CA 15-3 was quantified using IRMA kit. Clinical data were collected from patients’ records. Results: YBX-1 (p < 0.001), IL-6 (p < 0.001) and CA15-3 (p = 0.017, 0.001) were significantly elevated in metastatic and non-metastatic BC patients compared to healthy controls, however, only YBX-1 (p 0.001) showed a significant difference with cancer metastasis. Generally, YBX-1 and IL-6 were correlated with worse histological grade and late clinical stage in breast cancer patients and they were also associated with axillary lymph nodes involvement and positive vascular invasion in metastatic BC patients. Serum YBX-1 and IL-6 levels were positively correlated to each other (rs = 0.615, p < 0.001) and they showed high sensitivity and specificity compared to CA 15-3 (p < 0.001 and p = 0.004 for YBX-1 and IL-6 respectively) for predicting cancer metastasis. Conclusions: Serum YBX-1 and IL-6 are potential biomarkers of breast cancer patients with significant correlation with bad clinicopathological characteristics. Serum YBX-1 and IL-6 have superior sensitivity and specificity compared to CA15-3 and can serve as potential follow up and prognostic markers.
文摘Cancer patients frequently report a set of symptoms including fatigue, pain, and physiological and social distress. Families and other personal lay relations give proposals to take supportive drugs and supplemental nutrients, without professional knowledge about their actions. Internet search engines and social networks serve up most of the treatment proposals, opening wide possibilities for quackeries and predatory money-making practices. Medical professionals have a responsibility to clear this field and concentrate on patients’ well-being and personal needs. According to our approach, the integration of supportive and palliative care with conventional therapies needs a change of paradigm from tumour-driven to patient-driven treatment actions. Supportive/palliative care includes a broad spectrum of applied methods, including medications, nourishments, electrical effects, and psycho and social supports. Our goal is to discuss the possibilities for combining conventional oncotherapies with additional supportive/palliative care and to give suggestions on a professional basis.
基金funding from the Chinese Scholarship Council (J.L.)and the European Research Council (R.E.,ERC Consolidator Grant 726381).
文摘The controlled release of drugs using local ionizing radiation presents a promising approach for targeted cancer treatment,particularly when applied in concurrent radio-chemotherapy.In these approaches,radiation-generated reactive species often play an important role.However,the reactive species that can be used to trigger release have low yield and lack selectivity.Here,we demonstrate the generation of highly oxidative species when aqueous solutions containing low concentrations of organochlorides(such as chloroform)are irradiated with ionizing radiation at therapeutically relevant doses.These reactive species were identified as peroxyl radicals,which formed in a reaction cascade between organochlorides and aqueous electrons.We employed stilbene-based probes to investigate the oxidation process,showing double bond oxidation and cleavage.To translate this reactivity into a radiation-sensitive material,we synthesized a micelle-forming amphiphilic block copolymer that has stilbene as the linker between two blocks.Upon exposure to ionizing radiation,the oxidation of stilbene led to the cleavage of the polymer,which induces the dissociation of the block-copolymer micelles and the release of loaded drugs.
基金financially supported by the Key Research & Development Program of Jiangsu Province(No.BE2017102)
文摘（MnFe）2（P, Si）-type compounds are, to date, one of the best candidates for magnetic refrigeration and energy conversion applications due to the combination of giant magnetocaloric effect （MCE）, tunable working temperature range and low material cost. The giant MCE in the （Mn, Fe）2（P, Si）-type compounds originates from strong mag- netoelastic coupling, where the lattice degrees of freedom and spin degrees of freedom are efficiently coupled. The tunability of the phase transition, in terms of the critical temperature and the character of the phase transition, is essentially attributed to the changes in the magnetoelastic coupling in the （Mn, Fe）2（P, Si）-type compounds. In this review, not only the fundamentals of the magnetoelastic coupling but also the related practical aspects such as magnetocaloric performance, hysteresis issue and mechanical stability are discussed for the （Mn, Fe）2（P, Si）- type compounds. Additionally, some future fundamental studies on the MCE as well as possible ways of solving the hysteresis and fracture issues are proposed.
基金supported by the National Natural Science Foundation of China(Nos.51801102,U1832191,12004179,and 11974184)the Natural Science Foundation of Jiangsu Province(Nos.BK20180491 and BK20180418)+1 种基金the Open Fund of Large Facilities in Nanjing University of Science and Technologythe Guangdong-Hong Kong-Macao Joint Laboratory for Neutron Scattering Science and Technology。
文摘Magnetocaloric materials undergoing reversible phase transitions are highly desirable for magnetic refrigeration applications.(Mn,Fe)_(2)(P,Si)alloys exhibit a giant magnetocaloric effect accompanied by a magnetoelastic transition,while the noticeable irreversibility causes drastic degradation of the magnetocaloric properties during consecutive cooling cycles.In the present work,we performed a comprehensive study on the magnetoelastic transition of the(Mn,Fe)_(2)(P,Si)alloys by high-resolution transmission electron microscopy,in situ field-and temperature-dependent neutron powder diffraction as well as density functional theory calculations(DFT).We found a generalized relationship between the thermal hysteresis and the transition-induced elastic strain energy for the(Mn,Fe)_(2)(P,Si)family.The thermal hysteresis was greatly reduced from 11 to 1 K by a mere 4 at.%substitution of Fe by Mo in the Mn_(1.15)Fe_(0.80)P_(0.45)Si_(0.55)alloy.This reduction is found to be due to a strong reduction in the transition-induced elastic strain energy.The significantly enhanced reversibility of the magnetoelastic transition leads to a remarkable improvement of the reversible magnetocaloric properties,compared to the parent alloy.Based on the DFT calculations and the neutron diffraction experiments,we also elucidated the underlying mechanism of the tunable transition temperature for the(Mn,Fe)_(2)(P,Si)family,which can essentially be attributed to the strong competition between the covalent bonding and the ferromagnetic exchange coupling.The present work provides not only a new strategy to improve the reversibility of a first-order magnetic transition but also essential insight into the electron-spin-lattice coupling in giant magnetocaloric materials.
基金This work was in part funded by The Netherlands Organization for Scientific Research(NWO)by the Materials for Sustainability project SPEAR under Grant No.739.017.012.
文摘A novel protocol for the synthesis of perylene diimides(PDIs),by reacting perylene dianhydride(PDA)with aliphatic amines is reported.Full conversions were obtained at temperatures between 20 and 60℃,using DBU as the base in DMF or DMSO.A“green”synthesis of PDIs,that runs at higher temperatures,was developed using K_(2)CO_(3) in DMSO.
基金the Key International(Regional)Cooperative Research Project(No.81820108028)the National Natural Science Foundation of China(Nos.81521004,81922061,81973123,and 81803306)+2 种基金the Science Foundation for Distinguished Young Scholars of Jiangsu(No.BK20160046)the Priority Academic Program for the Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine).the National Cancer Institute,National Institutes of Health of USA through grants U01-CA063673,UM1-CA167462,and U01-CA167462.
文摘Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
文摘Phase separation during the lithiation of redox-active materials is a critical factor affecting battery performance,including energy density,charging rates,and cycle life.Accurate physical descriptions of these materials are necessary for understanding underlying lithiation mechanisms,performance limitations,and optimizing energy storage devices.This work presents an extended regular solution model that captures mutual interactions between sublattices of multi-sublattice battery materials,typically synthesized by metal substitution.We apply the model to phospho-olivine materials and demonstrate its quantitative accuracy in predicting the composition-dependent redox shift of the plateaus of LiMn_(y)Fe_(1-y)PO_(4)(LFMP),LiCo_(y)Fe_(1-y)PO_(4)(LFCP),LiCo_(x)Mn_(y)Fe_(1-y)PO_(4)(LFMCP),as well as their phase separation behavior.Furthermore,we develop a phase-field model of LFMP that consistently matches experimental data and identifies LiMn0.4Fe0.6PO4 as a superior composition that favors a solid solution phase transition,making it ideal for high-power applications.
基金This study is funded by the Comprehensive Cancer Center Munich(CCC-M)at the Partner Site“Klinikum rechts der Isar,Technische Universität München/Roman Herzog Cancer Center(RHCCC).
文摘Background:More than 25%of patients with solid cancers develop intracerebral metastases.Aside of surgery,radia-tion therapy(RT)is a mainstay in the treatment of intracerebral metastases.Postoperative fractionated stereotactic RT(FSRT)to the resection cavity of intracerebral metastases is a treatment of choice to reduce the risk of local recur-rence.However,FSRT has to be delayed until a sufficient wound healing is attained;hence systemic therapy might be postponed.Neoadjuvant stereotactic radiosurgery(SRS)might offer advantages over adjuvant FSRT in terms of better target delineation and an earlier start of systemic chemotherapy.Here,we conducted a study to find the maximum tolerated dose(MTD)of neoadjuvant SRS for intracerebral metastases.Methods:This is a single-center,phase I dose escalation study on neoadjuvant SRS for intracerebral metastases that will be conducted at the Klinikum rechts der Isar Hospital,Technical University of Munich.The rule-based traditional 3+3 design for this trial with 3 dose levels and 4 different cohorts depending on lesion size will be applied.The primary endpoint is the MTD for which no dose-limiting toxicities(DLT)occur.The adverse events of each participant will be evaluated according to the Common Terminology Criteria for Adverse Events(CTCAE)version 5.0 continuously during the study until the first follow-up visit(4-6 weeks after surgery).Secondary endpoints include local control rate,survival,immunological tumor characteristics,quality of life(QoL),CTCAE grade of late clinical,neurological,and neurocognitive toxicities.In addition to the intracerebral metastasis which is treated with neoadjuvant SRS and resection up to four additional intracerebral metastases can be treated with definitive SRS.Depending on the occurrence of DLT up to 72 patients will be enrolled.The recruitment phase will last for 24 months.Discussion:Neoadjuvant SRS for intracerebral metastases offers potential advantages over postoperative SRS to the resection cavity,such as better target volume definition with subsequent higher efficiency of eliminating tumor cells,and lower damage to surrounding healthy tissue,and much-needed systemic chemotherapy could be initiated more rapidly.
