bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pain and masochistic behaviour: The role of descending modulation
Authors: Baudic Sophie , Poindessous‐Jazat Frédérique , Bouhassira Didier 
Published: September 2022

AbstractBackgroundThe mechanisms of pain perception in individuals with masochistic behaviour (MB) remain poorly documented. We hypothesized that MB is associated with context‐specific changes in descending pain modulation.MethodsWe compared the effects of four standardized sets of images with positive (erotic), negative (mutilations), masochistic or neutral emotional valences on the RIII nociceptive reflex evoked by electrical stimulation of the sural nerve and recorded on the ipsilateral biceps femoris in 15 controls and 15 men routinely engaging in MB. We systematically assessed the RIII reflex threshold and recruitment curves (up to the tolerance threshold), thermal (heat and cold) pain thresholds measured on the upper and lower limbs and responses to the pain sensitivity questionnaire, to compare basal pain perception between our two groups of participants. We also assessed anxiety, depression, empathy, alexithymia, high sensation seeking and catastrophizing, to investigate their potential influence on the emotional modulation of pain.ResultsThermal pain thresholds, RIII reflex recruitment curves, and responses to the psychological and pain sensitivity questionnaires were similar in the two groups. Neutral, positive and negative images modulated the RIII reflex similarly in the two groups. By contrast, masochistic images induced a significant (p < 0.01) decrease in RIII reflex responses in subjects with MB, whereas it tended to increase these responses in control subjects.ConclusionsOur data suggest that psychological profile, basal pain sensitivity and the emotional modulation of pain are normal in individuals with MB but that these subjects selectively engage descending pain inhibition in the masochistic context.SignificanceDecrease pain perception related to masochistic behaviours is associated with specific activation of descending pain inhibition.
Remyelination in neuromyelitis optica spectrum disorder is promoted by edaravone through mTORC1 signaling activation
Authors: Luo Wenjing , Xu Huiming , Xu Li , Jiang Wei , Chen Chen , Chang Yanyu , Liu Chunxin , Tian Zhenming , Qiu Xiusheng , Xie Chichu , Li Xuejia , Chen Haijia , Lai Shuiqing , Wu Longjun , Cui Yaxiong , Tang Changyong , Qiu Wei 
Published: September 2022

AbstractNeuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory autoimmune disease of the central nervous system that is manifested as secondary myelin loss. Oligodendrocyte progenitor cells (OPCs) are the principal source of myelinating oligodendrocytes (OLs) and are abundant in demyelinated regions of NMOSD patients, thus possibly representing a cellular target for pharmacological intervention. To explore the therapeutic compounds that enhance myelination due to endogenous OPCs, we screened the candidate drugs in mouse neural progenitor cell (NPC)‐derived OPCs. We identified drug edaravone, which is approved by the Food and Drug Administration (FDA), as a promoter of OPC differentiation into mature OLs. Edaravone enhanced remyelination in organotypic slice cultures and in mice, even when edaravone was administered following NMO‐IgG‐induced demyelination, and ameliorated motor impairment in a systemic mouse model of NMOSD. The results of mechanistic studies in NMO‐IgG‐treated mice and the biopsy samples of the brain tissues of NMOSD patients indicated that the mTORC1 signaling pathway was significantly inhibited, and edaravone promoted OPC maturation and remyelination by activating mTORC1 signaling. Furthermore, pharmacological activation of mTORC1 signaling significantly enhanced myelin regeneration in NMOSD. Thus, edaravone is a potential therapeutic agent that promotes lesion repair in NMOSD patients by enhancing OPC maturation.
Does providing free internet access to low‐income households affect COVID‐19 spread?
Authors: Goetz Daniel 
Published: September 2022

AbstractThis paper evaluates whether a policy of providing free, in‐home Internet for lower‐income households can reduce COVID‐19 case rates among those households. Using data from a pilot program in Toronto, we find that deploying free public WiFi in large apartment blocks within a low‐income neighborhood leads to a 14.4% reduction in weekly cases in that neighborhood. Having in‐home WiFi reduces the propensity of residents to visit businesses in the arts, entertainment, and recreation category, suggesting that WiFi benefits residents by providing in‐home substitutes for leisure activities.
c‐Rel–dependent Chk2 signaling regulates the DNA damage response limiting hepatocarcinogenesis
Authors: Leslie Jack , Hunter Jill E. , Collins Amy , Rushton Amelia , Russell Lauren G. , Ramon‐Gil Erik , Laszczewska Maja , McCain Misti , Zaki Marco Y. W. , Knox Amber , Seow Yixin , Sabater Laura , Geh Daniel , Perkins Neil D. , Reeves Helen L. , Tiniakos Dina , Mann Derek A. , Oakley Fiona 
Published: September 2022

Background and Aims:
Hepatocellular carcinoma (HCC) is a leading cause of cancer‐related death. The NF‐κB transcription factor family subunit c‐Rel is typically protumorigenic; however, it has recently been reported as a tumor suppressor. Here, we investigated the role of c‐Rel in HCC.

Approach and Results:
Histological and transcriptional studies confirmed expression of c‐Rel in human patients with HCC, but low c‐Rel expression correlated with increased tumor cell proliferation and mutational burden and was associated with advanced disease. In vivo, global (Rel

−/−
) and epithelial specific (Rel

Alb
) c‐Rel knockout mice develop more tumors, with a higher proliferative rate and increased DNA damage, than wild‐type (WT) controls 30 weeks after N‐diethylnitrosamine injury. However, tumor burden was comparable when c‐Rel was deleted in hepatocytes once tumors were established, suggesting c‐Rel signaling is important for preventing HCC initiation after genotoxic injury, rather than for HCC progression. In vitro, Rel

−/−
hepatocytes were more susceptible to genotoxic injury than WT controls. ATM‐CHK2 DNA damage response pathway proteins were suppressed in Rel

−/−
hepatocytes following genotoxic injury, suggesting that c‐Rel is required for effective DNA repair. To determine if c‐Rel inhibition sensitizes cancer cells to chemotherapy, by preventing repair of chemotherapy‐induced DNA damage, thus increasing tumor cell death, we administered single or combination doxorubicin and IT‐603 (c‐Rel inhibitor) therapy in an orthotopic HCC model. Indeed, combination therapy was more efficacious than doxorubicin alone.

Conclusion:
Hepatocyte c‐Rel signaling limits genotoxic injury and subsequent HCC burden. Inhibiting c‐Rel as an adjuvant therapy increased the effectiveness of DNA damaging agents and reduced HCC growth.
Surgical Care Services in inaccessible zones: Targeted Palliative Care Accessibility Models for patients in resource‐limited settings
Authors: Shah Pritik A. , Tovani‐Palone Marcos Roberto 
Published: September 2022

AbstractThe coronavirus disease 2019 (COVID‐19) pandemic has caused a paradigm shift in the cancer care landscape, shifting from a palliative care approach to a need‐based approach. In these current and upcoming future times, patient‐ and community‐centred research becomes the cornerstone of collaborative assessment efforts for understanding and assessing Targeted Palliative Care (TPC) Accessibility Models for patients with oncological malignancies in resource‐limited settings. This short communication focuses on the models available for TPC for the continuation of care in oncological settings in resource‐limited geographic areas. Some programmes have used a Mixed Method Approach, highlighting their importance based on engagement volunteers and building trust and relationships in the community. Other studies have addressed the care system using a Rural Palliative Supportive Service Model for older adults living with life‐limiting chronic illness, showing that home‐based treatment for this population is feasible. Moreover, the Home Palliative Care Units (HPCU) model showed promising results in that patients cared for by HPCU had a fewer emergency visits and hospital admissions, in addition to being more likely to die at home with adequate palliation. During the ongoing pandemic, patients have experienced rapid clinical decline, requiring urgent conversations about their care wishes. They have been forced to make decisions on so‐called ‘Life and death’ issues. In this article we discuss the advantages, disadvantages, and possible changes implemented in the context of cancer surgical care in resource‐limited settings, in order to create a better assessment of geographic or demographic‐based, patient‐ and community‐centred TPC accessibility models for a more holistic development of cancer care programs.
Follow‐up the severity of abnormalities diagnosed in chest CT imaging of COVID‐19 patients: A cross‐sectional study
Authors: Honarmandpour Fatemeh , Jahangirimehr Azam , Tahmasbi Marziyeh , Khalighi Azam , Honarmandpour Azam 
Published: September 2022

AbstractBackground and AimsThis study aimed to evaluate the severity of diagnosed lung abnormalities of coronavirus disease 2019 (COVID‐19) patients based on the pre‐and postrecovery follow‐up chest computed tomography (CT) scan findings done at regular intervals.MethodsThis cross‐sectional study was performed in three phases. The severity of lung abnormalities was recorded and compared based on the initial and follow‐up chest CT findings carried out pre‐and at regular intervals (3 and 6 months) of postrecovery of COVID‐19 patients. Statistical data analysis was conducted using SPSS‐Version 26. Pearson Chi‐square test was used to analyze the results. p‐value < 0.05 was considered statistically significant.ResultsRegarding the initial chest CT findings, although ground‐glass opacity (GGO) was observed as the most common lung lesion, almost all the evaluated COVID‐19 patients had multiple lung lesions and involvements, especially with more involvement of the lower lobes. concerning the frequency of lung lesions and involvements in all phases of the study, almost no statistically significant differences were observed between male and female COVID‐19 patients and different age groups. However, older age groups had relatively more lung abnormalities due to Covid‐19 based on initial CT images which take more time to be eliminated. Lung abnormalities of Covid‐19 patients decreased significantly during the follow ups based on chest CT findings at different study phases.ConclusionAccording to evaluated pre‐ and post‐recovery chest CT scans, the frequency of lung lesions and lung involvement distribution decreased significantly in COVID‐19 patients, 3 and 6 months after recovery, and most of the recovered patients had no lung lesions or involvement anymore.
Fatigue performance investigation on the automotive welded structure under damped loads using the Taguchi method
Authors: Amarir Imane , Mounir Hamid , Rajad Omar , Amadane Yassine 
Published: September 2022

AbstractIn the present paper, a three‐dimensional numerical model has been built using ANSYS code to analyze the static and fatigue behavior of a welded design based on four rectangular profiles under damped loads for automotive application. The fatigue of the proposed design is generally influenced by a number of factors. The aim of this study is to investigate the effect of the load level, the stress ratio, the mean stress theory, the geometry size, the weld bead height, the temperature of the weld bead on the durability (P1), and the maximum of von Mises stress (P2) at the critical areas in the welded structure. As well as the length and the stiffness of the spring have been furtherly investigated. For this purpose, the application of the Taguchi method with computational simulation was performed for the target to determine the optimum operating parameters conditions. The results indicated that the optimum levels yielding a higher performance for P1 and P2 were (L1, L2, L2, L3, L1, L1, L3, and L3) and (L2, L3, L3, L3, L3, L3, L3, and L2), respectively. Thus, it revealed that the weld temperature was the predominant parameter influencing P1 and the mean stress theory factor was the most significant parameter influencing P2. This study led to defining a regression equation relating the output parameters with the selected factors. Consequently, the percentage error between regression equation calculations and computational outputs of fatigue life and maximum von Mises stress corresponding to the most optimal combinations obtained from Taguchi calculations was 0.92% and 0.63%, respectively. In fact, several parameters have been employed in this durability assessment to characterize the behavior of welded rectangular profiles prototype to predict the overall behavior of the suspension system of the automotive.
Uncertainty in high‐resolution hydrological projections: Partitioning the influence of climate models and natural climate variability
Authors: Moraga Jorge Sebastián , Peleg Nadav , Molnar Peter , Fatichi Simone , Burlando Paolo 
Published: September 2022

AbstractA major challenge in assessing the impacts of climate change on hydrological processes lies in dealing with large degrees of uncertainty in the future climate projections. Part of the uncertainty is owed to the intrinsic randomness of climate phenomena, which is considered irreducible. Additionally, modelling the response of hydrological processes to the changing climate requires the use of a chain of numerical models, each of which contributes some degree of uncertainty to the final outputs. As a result, hydrological projections, despite the progressive increase in the accuracy of the models along the chain, still display high levels of uncertainty, especially at small temporal and spatial scales. In this work, we present a framework to quantify and partition the uncertainty of hydrological processes emerging from climate models and internal variability, across a broad range of scales. Using the example of two mountainous catchments in Switzerland, we produced high‐resolution ensembles of climate and hydrological data using a two‐dimensional weather generator (AWE‐GEN‐ 2d) and a distributed hydrological model (TOPKAPI‐ETH). We quantified the uncertainty in hydrological projections towards the end of the century through the estimation of the values of signal‐to‐noise ratios (STNR). We found small STNR absolute values (<1) in the projection of annual streamflow for most sub‐catchments in both study sites that are dominated by the large natural variability of precipitation (explains ~70% of total uncertainty). Furthermore, we investigated in detail specific hydrological components that are critical in the model chain. For example, snowmelt and liquid precipitation exhibit robust change signals, which translates into high STNR values for streamflow during warm seasons and at higher elevations, together with a larger contribution of climate model uncertainty. In contrast, projections of extreme high flows show low STNR values due to large internal climate variability across all elevations, which limits the potential for narrowing their estimation uncertainty.
Fabrication of macroporous apatite bone cements for non‐load bearing orthopedic applications
Authors: Dewangan Vimal Kumar , Sampath Kumar Trichirapalli Subramaniam , Doble Mukesh , Daniel Varghese Viju 
Published: September 2022

AbstractCalcium deficient hydroxyapatite (CDHA)‐based apatite forming bone cements are well known for their bioactivity and bioresorbability. The formulation of CDHA‐based cements with improved macroporosity, injectability, and resorbability has been investigated. The solid phase consists of nanocrystalline hydroxyapatite (HA) and tricalcium phosphate (β‐TCP). The liquid phase is diluted acetic acid with disodium hydrogen phosphate as binding accelerator along with gelatin and chitosan to improve the injectability. A porogen agent either mannitol (as solid porogen) or polysorbate (as liquid porogen) is also used to improve the porosity. All combined in fine‐tuned composition results in optimal bone cements. The cement sets within the clinically preferred setting time (≤20 min) and injectability (>70%) and also stable at physiological pH (i.e., ~7.3–7.4). The XRD and FT‐IR analysis confirmed the formation of CDHA phase on day 7 when the after‐set cement immersed under phosphate buffer solution (PBS) at physiological conditions. The cements were found to have acceptable compressive strength for trabecular bone substitute. The cements were macroporous in nature with average pore size between 50 and 150 μm and were interconnected as confirmed by SEM, micro‐CT and MIP analysis. The prepared cements are degradable up to 22% and 19% in simulated body fluid and PBS respectively within 10 weeks of immersion at physiological conditions. The cements exhibit higher viability (%) (>110%) with L929 and MG63 cells compared to the control after 3 days of incubation. They also show increased proliferation, well spreading and extended filopodia with MG63 cells. Overall, the developed apatite forming bone cements seems to be suitable for low or non‐load bearing orthopedic applications.
Hydrogen sulfide attenuates uranium‐induced kidney cells pyroptosis via upregulation of PI3K/AKT/mTOR signaling
Authors: Hu Qiaoni , Zhang Rui , Zheng Jifang , Song Menghui , Gu Chaohao , Li Wanting 
Published: September 2022

AbstractWe have identified that hydrogen sulfide (H2S), a gaseous mediator, plays a crucial role in antioxidative, anti‐inflammatory, and cytoprotective effects on uranium (U)‐triggered rat nephrotoxicity. Pyroptosis is a special mode of inflammation and programmed cell death involved in the activation of inflammasome and Caspase‐1 and the release of inflammatory cytokines. This study aims to confirm whether H2S can alleviate U‐induced rat NRK‐52Ecell pyroptosis and to investigate the H2S underlying regulatory mechanism. Our results indicate that pretreatment with NaHS (an H2S donor) significantly inhibited U‐increased reactive oxygen species level, NLRP3, apoptosis‐related speck‐like protein consisting of a caspase recruitment domain (ASC), and cleaved Caspase‐1 proteins expression, gasdermin D messenger RNA (GSDMD mRNA) expression, interleukin (IL)−1β and IL‐18 contents, lactate dehydrogenase leakage, and numbers of double‐positive dying kidney cells. NaHS application evidently augmented phosphorylated PI3K, AKT, and mTOR expression as well as ratios of their respective phosphorylation to the corresponding total proteins which were downregulated by U treatment. But, LY294002 (a PI3K inhibitor) administration effectively abrogated the consequences of NaHS on the levels of p‐PI3K, cleaved Caspase‐1, ASC and NLRP3 proteins, GSDMD mRNA expression, and (IL)‐1β and IL‐18 contents. Simultaneously, LY294002 significantly reversed the effects of NaHS on U‐induced pyroptosis rate and cytotoxicity. Taken together, these results indicate that H2S ameliorated U‐triggered NRK‐52Ecells pyroptosis via upregulation of PI3K/AKT/mTOR pathway, suggesting a novel role for H2S in the management of nephrotoxicity caused by U exposure.
An immunogold single extracellular vesicular RNA and protein (AuSERP) biochip to predict responses to immunotherapy in non‐small cell lung cancer patients
Authors: Nguyen Luong T. H. , Zhang Jingjing , Rima Xilal Y. , Wang Xinyu , Kwak Kwang Joo , Okimoto Tamio , Amann Joseph , Yoon Min Jin , Shukuya Takehito , Chiang Chi‐Ling , Walters Nicole , Ma Yifan , Belcher Donald , Li Hong , Palmer Andre F. , Carbone David P. , Lee L. James , Reátegui Eduardo 
Published: September 2022

AbstractConventional PD‐L1 immunohistochemical tissue biopsies only predict 20%–40% of non‐small cell lung cancer (NSCLC) patients that will respond positively to anti‐PD‐1/PD‐L1 immunotherapy. Herein, we present an immunogold biochip to quantify single extracellular vesicular RNA and protein (AuSERP) as a non‐invasive alternative. With only 20 μl of purified serum, PD‐1/PD‐L1 proteins on the surface of extracellular vesicles (EVs) and EV PD‐1/PD‐L1 messenger RNA (mRNA) cargo were detected at a single‐vesicle resolution and exceeded the sensitivities of their bulk‐analysis conventional counterparts, ELISA and qRT‐PCR, by 1000 times. By testing a cohort of 27 non‐responding and 27 responding NSCLC patients, AuSERP indicated that the single‐EV mRNA biomarkers surpass the single‐EV protein biomarkers in predicting patient responses to immunotherapy. Dual single‐EV PD‐1/PD‐L1 mRNA detection differentiated responders from non‐responders with an accuracy of 72.2% and achieved an NSCLC diagnosis accuracy of 93.2%, suggesting the potential for AuSERP to provide enhanced immunotherapy predictions and cancer diagnoses within the clinical setting.
A multinational study of acute and long‐term outcomes of Type 1 galactosemia patients who carry the S135L (c.404C > T) variant of GALT
Authors: Katler Quinton S. , Stepien Karolina M. , Paull Nathan , Patel Sneh , Adams Michael , Balci Mehmet Cihan , Berry Gerard T. , Bosch Annet M. , DeLaO Angela , Demirbas Didem , Edman Julianna , Ficicioglu Can , Goff Melanie , Hacker Stephanie , Knerr Ina , Lancaster Kristen , Li Hong , Mendelsohn Bryce A. , Nichols Brandi , de Rezende Pinto Wladimir Bocca Vieira , Rocha Júlio César , Rubio‐Gozalbo M. Estela , Saad‐Naguib Michael , Scholl‐Buergi Sabine , Searcy Sarah , de Souza Paulo Victor Sgobbi , Wittenauer Angela , Fridovich‐Keil Judith L. 
Published: September 2022

AbstractPatients with galactosemia who carry the S135L (c.404C > T) variant of galactose‐1‐P uridylyltransferase (GALT), documented to encode low‐level residual GALT activity, have been under‐represented in most prior studies of outcomes in Type 1 galactosemia. What is known about the acute and long‐term outcomes of these patients, therefore, is based on very limited data. Here, we present a study comparing acute and long‐term outcomes of 12 patients homozygous for S135L, 25 patients compound heterozygous for S135L, and 105 patients homozygous for two GALT‐null (G) alleles. This is the largest cohort of S135L patients characterized to date. Acute disease following milk exposure in the newborn period was common among patients in all 3 comparison groups in our study, as were long‐term complications in the domains of speech, cognition, and motor outcomes. In contrast, while at least 80% of both GALT‐null and S135L compound heterozygous girls and women showed evidence of an adverse ovarian outcome, prevalence was only 25% among S135L homozygotes. Further, all young women in this study with even one copy of S135L achieved spontaneous menarche; this is true for only about 33% of women with classic galactosemia. Overall, we observed that while most long‐term outcomes trended milder among groups of patients with even one copy of S135L, many individual patients, either homozygous or compound heterozygous for S135L, nonetheless experienced long‐term outcomes that were not mild. This was true despite detection by newborn screening and both early and life‐long dietary restriction of galactose. This information should empower more evidence‐based counseling for galactosemia patients with S135L.