bluuebunny/crossref_metadata_2025_split huggingface dataset:
How do patients with Alzheimer's disease imagine their pain?
Authors: Borg Céline , Sala Emilie , Chainay Hanna , Labouré Julien , Getenet Jean‐Claude , Dorey Jean‐Michel , Laurent Bernard , Rouch Isabelle 
Published: October 2020

AbstractIntroductionPain is underdiagnosed and undertreated in patients with Alzheimer's disease (AD). Pain management is of major importance in this population to limit behavioural and functional consequences. Our study aimed to assess the capacity of AD patients to represent pain using a questionnaire exploring daily painful situations and to determine the most appropriate pain scale assessment.MethodsTwenty‐eight patients with mild AD, 21 with moderate AD and 28 matched controls underwent the Situation Pain Questionnaire (SP‐Q) and assessed imaginary pain with four pain scales. Two scores were compared between the three groups: the P(A) discrimination score and the response bias β score. P(A) reflects the degree of discrimination between high‐pain and low‐pain events, whereas the β score means the degree to which situations are considered as painful.ResultsOur results showed that AD patients hardly discriminated the high‐ from low‐pain events. Compared to controls, the mean P(A) score was significantly lower for Mild AD (p < 0.03) and Moderate AD (p < 0.004). In addition, the β score indicated that the response bias is higher for AD patients (p < 0.01) in that they overestimated the level of pain.ConclusionThe present results suggest that patients with Mild and Moderate AD are able to recognize and assess an imagined painful situation even though their pain tolerance is lower than that of controls. The pain scales used should be chosen according to the cognitive, sensorial and personal profiles of the patients.SignificanceThe present research is significant because it examines how patients with Alzheimer’s disease understand and assess painful situations. Cognitive impairments can modify this ability. Pain is a sensory and subjective experience and to define its feeling can help us in our clinical practice.
The Time of Crochet: Interruption, Plasticity, and the Domestic in Delhi
Authors: Sehdev Megha Sharma 
Published: October 2020

AbstractRecent feminist writings have likened crochet to coral reefs and other ecological forms that privilege a hyperbolic and expansive creativity. Looping text with a series of photographs taken by the author between 2013 and 2016, this essay describes women's crochet in Delhi, India as a form that intensively manipulates surfaces rather than expanding along them. The proximate action of crochet – structured and expressive, domestic and otherworldly – imparts a disruptive plasticity to surroundings. Women's domestic lives are sites of sensory and temporal attunement, a wakefulness to the self, mediated by this plasticity of crochet in both practice and form.
Sensitivity analysis of heat and mass transfer characteristics during forced‐air cooling process of peaches on different air‐inflow velocities
Authors: Chen Ying‐Min , Song Hai‐Yan , Chen Zhen‐Shi , Zhao Rui , Su Qin , Jin Peng‐Yong , Sun Yi‐Shu , Wang Hao 
Published: October 2020

AbstractPeach is one of the most perishable fruits. During forced‐convection cooling, the heat sources (respiratory and evaporative latent heat) internal to freshly harvested peaches have a remarkable influence on its evaluation of cooling characteristics with respect to various cooling strategies. Therefore, to improve the accuracy of simulation results in peaches cooling, the term of heat source was coded as detailed procedures and included into a computational fluid dynamics (CFD) model. By comparing the temperature simulated with and without considering these heat sources, it is found that a reasonable decrease in variations of cooling performances is obtained with sustained increase in air‐inflow velocities. A maximum discrepancy in peaches volume‐weighted average temperature (∆Tvwa‐max) is mainly concentrated in 0.1–0.3°C when the air‐inflow velocity not exceeds 1.7 m/s, and its corresponded 7/8ths cooling time (SECT) is also prolonged by 1–6 min. This means that, below 1.7 m/s, these heat sources should be added as a term into the heat transfer equations for modifying the mathematical model inside peaches computational domain. Furthermore, the feasibility of this modeling method is confirmed by a great agreement with experiments, and its modified model has a higher accuracy with the decreased RMSE and MAPE values of 6.90%–11.26% and 7.28%–12.95%, respectively.
Germline testing for homologous recombination repair genes—opportunities and challenges
Authors: Hirsch Steffen , Gieldon Laura , Sutter Christian , Dikow Nicola , Schaaf Christian P. 
Published: October 2020

AbstractPathogenic variants in theBRCA1andBRCA2genes are well known causes of hereditary breast and ovarian cancer. Other genes involved in the homologous recombination pathway can also be associated with increased probability of cancer development, for example, breast and ovarian cancer, prostate and pancreatic cancer, colorectal cancer, and even childhood tumors like medulloblastoma. Traditionally, patients and families likely to harbor a genetic predisposition have been identified using personal and family history. Several checklists and risk prediction tools have proven to be useful in the clinic. Through the widespread application of next generation sequencing of tumor tissue, a growing number of individuals with genetic cancer predisposition is now identified molecularly, even in the absence of a suggestive family history. Any constitutional variant identified during molecular genetic testing has to be assessed for its relevance, both functionally and in the context of patient phenotype. Variant curation is time consuming, but has been increasingly standardized by introduction of several guidelines to allow reliable and reproducible classification of constitutional variants. Variant classification by expert panels using data mining tools, evidence‐based decision trees and gene specific criteria represents the gold standard. Participation of geneticists in molecular tumor boards facilitates the curation of potential constitutional variants, germline validation and thus directing the patient to appropriate counselling and care pathways. Due to the high relevance of germline variants for treatment and surveillance of the index patient and predictive testing and surveillance of relatives, only pathogenic or likely pathogenic variants must be used for clinical decision‐making.
Microglial reduction of colony stimulating factor‐1 receptor expression is sufficient to confer adult onset leukodystrophy
Authors: Biundo Fabrizio , Chitu Violeta , Shlager Gabriel G. L. , Park Eun S. , Gulinello Maria E. , Saha Kusumika , Ketchum Harmony C. , Fernandes Christopher , Gökhan Şölen , Mehler Mark F. , Stanley E. Richard 
Published: October 2020

AbstractAdult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a dementia resulting from dominantly inherited CSF1R inactivating mutations. The Csf1r+/− mouse mimics ALSP symptoms and pathology. Csf1r is mainly expressed in microglia, but also in cortical layer V neurons that are gradually lost in Csf1r+/− mice with age. We therefore examined whether microglial or neuronal Csf1r loss caused neurodegeneration in Csf1r+/− mice. The behavioral deficits, pathologies and elevation of Csf2 expression contributing to disease, previously described in the Csf1r+/− ALSP mouse, were reproduced by microglial deletion (MCsf1rhet mice), but not by neural deletion. Furthermore, increased Csf2 expression by callosal astrocytes, oligodendrocytes, and microglia was observed in Csf1r+/− mice and, in MCsf1rhet mice, the densities of these three cell types were increased in supraventricular patches displaying activated microglia, an early site of disease pathology. These data confirm that ALSP is a primary microgliopathy and inform future therapeutic and experimental approaches.
Dissimilarity of functional connectivity uncovers the influence of participant's motion in functional magnetic resonance imaging studies
Authors: Yang Lili , Wu Bo , Fan Linyu , Huang Shishi , Vigotsky Andrew D. , Baliki Marwan N. , Yan Zhihan , Apkarian A. Vania , Huang Lejian 
Published: October 2020

AbstractHead motion is a major confounding factor impairing the quality of functional magnetic resonance imaging (fMRI) data. In particular, head motion can reduce analytical efficiency, and its effects are still present even after preprocessing. To examine the validity of motion removal and to evaluate the remaining effects of motion on the quality of the preprocessed fMRI data, a new metric of group quality control (QC), dissimilarity of functional connectivity, is introduced. Here, we investigate the association between head motion, represented by mean framewise displacement, and dissimilarity of functional connectivity by applying four preprocessing methods in two independent resting‐state fMRI datasets: one consisting of healthy participants (N = 167) scanned in a 3T GE‐Discovery 750 with longer TR (2.5 s), and the other of chronic back pain patients (N = 143) in a 3T Siemens Magnetom Prisma scanner with shorter TR (0.555 s). We found that dissimilarity of functional connectivity uncovers the influence of participant's motion, and this relationship is independent of population, scanner, and preprocessing method. The association between motion and dissimilarity of functional connectivity, and how the removal of high‐motion participants affects this association, is a new strategy for group‐level QC following preprocessing.
Regulatory review time and pharmaceutical research and development
Authors: Chorniy Anna , Bailey James , Civan Abdulkadir , Maloney Michael 
Published: October 2020

AbstractIn the United States, all newly developed drugs undergo a lengthy review process conducted by the US Food and Drug Administration (FDA). These regulatory delays have direct immediate costs for drug manufacturers and patients waiting for treatment. Under certain market conditions, regulatory delays may also affect future research and development (R&D) strategies of pharmaceutical companies. To estimate the magnitude of this effect, we match data on drugs in the development pipeline in 2006 to data that we collect on FDA review times for all drugs approved between 1999 and 2005. Employing a rich and novel set of controls that affect drug R&D decisions and, potentially, regulatory review lags, we find that on average, three additional months of delay result in one fewer drug in development in that drug category. Our results suggest that the length of the regulatory delay matters for pharmaceutical firms' R&D decisions and that the firms are likely unable to pass on these costs onto consumers.
Mucosal‐Associated Invariant T Cell Dysregulation Correlates With Conjugated Bilirubin Level in Chronic HBV Infection
Authors: Liu Yu , Zhu Peng , Wang Wei , Tan Xiaosheng , Liu Chuanqiao , Chen Yingshan , Pei Rongjuan , Cheng Xue , Wu Mi , Guo Qing , Liang Hongmei , Liang Zhihui , Liu Jia , Xu Yang , Wu Xiongwen , Weng Xiufang 
Published: October 2020

Background and Aims
Mucosal‐associated invariant T (MAIT) cells are nonconventional T cells restricted to major histocompatibility complex class I–related protein 1 (MR1). They are highly abundant in human liver and activated by T‐cell receptor (TCR)‐dependent and TCR‐independent mechanisms to exhibit rapid, innate‐like effector responses. However, the roles of MAIT cells in chronic HBV infection are still open for study. This study aims to test their antiviral potential and investigate their dynamic changes and regulating factors during chronic HBV infection.

Approach and Results
Blood samples from 257 chronic HBV‐infected patients were enrolled, and nontumor liver specimens were collected from 58 HBV‐infected HCC patients. Combining cell‐culture experiments and human data, we showed that MAIT cells had strong cytotoxicity against HBV‐transfected hepatocytes in an MR1‐dependent way. However, circulating and hepatic MAIT cells in HBV‐infected patients decreased significantly compared to controls. Correlation analysis suggested that MAIT cell frequency was associated with disease progression and inversely correlated with serum‐conjugated bilirubin level. In particular, conjugated bilirubin not only directly promoted MAIT cell activation and apoptosis, but also impaired TCR‐induced proliferation and expansion of MAIT cells, which could be partially rescued by IL‐2 in the absence of conjugated bilirubin. Despite that MAIT cells from patients with high conjugated bilirubin levels showed decreased cytokine‐producing capacity, the increased TCR‐dependent antiviral cytokine production suggested MAIT cells as an important guardian of chronic HBV with high conjugated bilirubin.

Conclusions
We reveal the MR1‐dependent, anti‐HBV potential of MAIT cells and identify conjugated bilirubin as a major factor dysregulating its frequency and function in chronic HBV‐infected patients, suggesting a therapeutic target for MAIT‐cell–based immunity against chronic HBV infection.
Water balance model as a tool for building participation and joint water use promotion at the river basin level*
Authors: Supriyasilp Thanaporn , Pongput Kobkiat 
Published: October 2020

AbstractTo promote collaboration on water management between farmers and government agencies, both parties must have a mutual understanding of the measurement and management of available water resources using existing infra‐ and non‐infrastructure management tools. They are required to provide collaborative water management through appropriate technology, with capacity building and knowledge management. In this study, the water balance model was used as a tool to induce participation and the promotion of a joint water use at the river basin level. The amount and proportion of water use from different types of water sources were calculated based on this water balance model. Moreover, farmers were encouraged to help with water flow measurements using technologies and principles that were simple but accurate in terms of engineering aspects. According to the analyses of water use proportions, a large amount of water from pumping stations was used during the dry season at high cost. When aware of the proportion of water used, farmers collaboratively established guidelines on an effective water management in the area, including large‐scale viewpoints applicable beyond the actual areas. Overall, these guidelines will eventually bring positive results to other downstream water users.
Fructose‐1,6‐bisphosphate induces generation of reactive oxygen species and activation of p53‐dependent cell death in human endometrial cancer cells
Authors: Costa Bruna Pasqualotto , Nassr Marcella Tornquist , Diz Fernando Mendonça , Carlessi Leonardo Pfeiff , Fernandes Krist Helen Antunes , Nunes Fernanda Bordignon , Branchini Gisele , de Oliveira Jarbas Rodrigues 
Published: October 2020

AbstractFructose‐1,6‐bisphosphate (F1,6BP), an intermediate of the glycolytic pathway, has been found to play a promising anticancer effect; nevertheless, the mechanisms involved remain poorly understood. The present study aimed to evaluate the effect and mechanisms of F1,6BP in a human endometrial cancer cell line (Ishikawa). F1,6BP showed an antiproliferative and non‐cytotoxic effect on endometrial cancer cells. These effects are related to the increase in reactive oxygen species (ROS) levels and mitochondrial membrane potential (ΔΨm). These harmful stimuli trigger the upregulation of the expression of pro‐apoptotic genes (p53 and Bax), leading to the reduction of cell proliferation through inducing programmed cell death by apoptosis. Furthermore, F1,6BP‐treated cells had the formation of autophagosomes induced, as well as a decrease in their proliferative capacity after withdrawing the treatment. Our results demonstrate that F1,6BP acts as an anticancer agent through the generation of mitochondrial instability, loss of cell function, and p53‐dependent cell death. Thus, F1,6BP proves to be a potential molecule for use in the treatment against endometrial cancer.
Ferritin in the coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis
Authors: Cheng Linlin , Li Haolong , Li Liubing , Liu Chenxi , Yan Songxin , Chen Haizhen , Li Yongzhe 
Published: October 2020

AbstractObjectiveThe coronavirus disease 2019 (COVID‐19) has rapidly developed into a pandemic. Increased levels of ferritin due to cytokine storm and secondary hemophagocytic lymphohistiocytosis were found in severe COVID‐19 patients. Therefore, the aim of this study was to determine the role of ferritin in COVID‐19.MethodsStudies investigating ferritin in COVID‐19 were collected from PubMed, EMBASE, CNKI, SinoMed, and WANFANG. A meta‐analysis was performed to compare the ferritin level between different patient groups: non‐survivors versus survivors; more severe versus less severe; with comorbidity versus without comorbidity; ICU versus non‐ICU; with mechanical ventilation versus without mechanical ventilation.ResultsA total of 52 records involving 10 614 COVID‐19‐confirmed patients between December 25, 2019, and June 1, 2020, were included in this meta‐analysis, and 18 studies were included in the qualitative synthesis. The ferritin level was significantly increased in severe patients compared with the level in non‐severe patients [WMD 397.77 (95% CI 306.51‐489.02), P < .001]. Non‐survivors had a significantly higher ferritin level compared with the one in survivors [WMD 677.17 (95% CI 391.01‐963.33), P < .001]. Patients with one or more comorbidities including diabetes, thrombotic complication, and cancer had significantly higher levels of ferritin than those without (P < .01). Severe acute liver injury was significantly associated with high levels of ferritin, and its level was associated with intensive supportive care, including ICU transfer and mechanical ventilation.ConclusionsFerritin was associated with poor prognosis and could predict the worsening of COVID‐19 patients.
Cell autonomous requirement of neurofibromin (Nf1) for postnatal muscle hypertrophic growth and metabolic homeostasis
Authors: Wei Xiaoyan , Franke Julia , Ost Mario , Wardelmann Kristina , Börno Stefan , Timmermann Bernd , Meierhofer David , Kleinridders Andre , Klaus Susanne , Stricker Sigmar 
Published: October 2020

AbstractBackgroundNeurofibromatosis type 1 (NF1) is a multi‐organ disease caused by mutations in neurofibromin 1 (NF1). Amongst other features, NF1 patients frequently show reduced muscle mass and strength, impairing patients' mobility and increasing the risk of fall. The role of Nf1 in muscle and the cause for the NF1‐associated myopathy are mostly unknown.MethodsTo dissect the function of Nf1 in muscle, we created muscle‐specific knockout mouse models for NF1, inactivating Nf1 in the prenatal myogenic lineage either under the Lbx1 promoter or under the Myf5 promoter. Mice were analysed during prenatal and postnatal myogenesis and muscle growth.ResultsNf1Lbx1 and Nf1Myf5 animals showed only mild defects in prenatal myogenesis. Nf1Lbx1 animals were perinatally lethal, while Nf1Myf5 animals survived only up to approximately 25 weeks. A comprehensive phenotypic characterization of Nf1Myf5 animals showed decreased postnatal growth, reduced muscle size, and fast fibre atrophy. Proteome and transcriptome analyses of muscle tissue indicated decreased protein synthesis and increased proteasomal degradation, and decreased glycolytic and increased oxidative activity in muscle tissue. High‐resolution respirometry confirmed enhanced oxidative metabolism in Nf1Myf5 muscles, which was concomitant to a fibre type shift from type 2B to type 2A and type 1. Moreover, Nf1Myf5 muscles showed hallmarks of decreased activation of mTORC1 and increased expression of atrogenes. Remarkably, loss of Nf1 promoted a robust activation of AMPK with a gene expression profile indicative of increased fatty acid catabolism. Additionally, we observed a strong induction of genes encoding catabolic cytokines in muscle Nf1Myf5 animals, in line with a drastic reduction of white, but not brown adipose tissue.ConclusionsOur results demonstrate a cell autonomous role for Nf1 in myogenic cells during postnatal muscle growth required for metabolic and proteostatic homeostasis. Furthermore, Nf1 deficiency in muscle drives cross‐tissue communication and mobilization of lipid reserves.
Galactose treatment of a PGM1 patient presenting with restrictive cardiomyopathy
Authors: Donoghue Sarah E. , White Susan M. , Tan Tiong Yang , Kowalski Remi , Morava Eva , Yaplito‐Lee Joy 
Published: October 2020

AbstractWe report a patient diagnosed with PGM1‐CDG at 11 years of age after two biallelic likely pathogenic variants in PGM1 were found on research genomic sequencing. To our knowledge, he is the first patient with PGM1‐CDG to be reported with a restrictive cardiomyopathy. Other clinical manifestations included cleft palate, asymptomatic elevated transaminases, intellectual disability and myopathy resulting in exercise intolerance. He was trialed on oral galactose therapy in increasing doses for 18 weeks to assess if there was any biochemical and clinical benefit. His galactose was continued for a further 9 months beyond the initial galactose treatment period due to improvements in exercise tolerance and myopathy. Treatment with galactose demonstrated an improvement in liver function and myopathy with improved exercise tolerance. Treatment with galactose for 15 months did not change heart function and exercise stress test results were stable.
Estimated radiation doses to ovarian and uterine organs in breast cancer irradiation using radio‐photoluminescent glass dosimeters (RPLDs)
Authors: Oonsiri Puntiwa , Vannavijit Chulee , Wimolnoch Mananchaya , Suriyapee Sivalee , Saksornchai Kitwadee 
Published: October 2020

AbstractIntroductionThe well‐being of breast cancer patients is essential, especially fertility in patients of reproductive age. The objective of this study was to estimate the radiation doses to the ovaries and uterus for different treatment techniques of breast cancer irradiation using radio‐photoluminescent glass dosimeters (RPLDs).MethodsA Farmer‐type ionisation chamber (IBA FC‐65G) and RPLDs were used to measure in‐ and out‐of‐field radiation doses in a solid water phantom. The field sizes were set to 10 × 10 cm2and 8 × 17 cm2with the central axis at out‐of‐field measurement distances of 30 or 50 cm. The Rando phantom’s left breast was planned using four different techniques: two tangential standard fields with and without electronic tissue compensator (E‐comp) techniques, intensity‐modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). The radiation doses in the ipsilateral ovary, contralateral ovary and uterus were measured using RPLDs.ResultsThe percentage ratio of out of field to in field was affected by distance from the central axis to the point of measurement, in addition to the field sizes associated with collimator scatter. Advanced techniques such as IMRT and VMAT produced higher doses to the ovaries and uterus. The estimated results of the worst‐case scenario for the ipsilateral ovary, contralateral ovary and uterus were 0.84% (42 cGy), 0.62% (31 cGy) and 0.76% (38 cGy), respectively, for a 5000 cGy prescription dose.ConclusionThe lowest to highest out‐of‐field radiation doses to the ovarian and uterine organs from breast irradiation were the two tangential field techniques, VMAT and IMRT. These advanced techniques yielded higher radiation leakage, which potentially contributed to the out‐of‐field radiation dose.