bluuebunny/crossref_metadata_2025_split huggingface dataset:
TREM2 interacts with TDP-43 and mediates microglial neuroprotection against TDP-43-related neurodegeneration
Authors: Xie Manling , Liu Yong , Zhao Shuyi , Zhang Lingxin , Bosco Dale , Pang Yuan-Ping , Sheth Udit , Martens Yuka , Zhao Na , Liu Chia-Chen , Zhuang Yongxian , Wang Liewei , Dickson Dennis , Mattson Mark , Bu Guojun , Wu Long-Jun 
Published: January 2021

Abstract
Triggering receptor expressed on myeloid cell 2 (TREM2) is a surface receptor that, in the central nervous system, is exclusively expressed on microglia. TREM2 variants have been linked to increased risk for neurodegenerative diseases, but the functional effects of microglial TREM2 remain largely unknown. To this end, we investigated TAR-DNA binding protein 43 kDa (TDP-43)-related neurodegenerative disease via viral-mediated expression of human TDP-43 protein (hTDP-43) in mice or inducible expression of hTDP43 with defective nuclear localization signals in transgenic mice. We found that TREM2 deficiency impaired microglia phagocytic clearance of pathological TDP-43, and enhanced neuronal damage and motor function impairments. Mass cytometry analysis revealed that hTDP-43 induced a TREM2-dependent subpopulation of microglia with high CD11c expression and higher phagocytic ability. Using mass spectrometry, we further demonstrated an interaction between TDP-43 and TREM2, in vitro and in vivo, in hTDP-43-expressing transgenic mouse brains. We computationally identified the region within hTDP-43 that interacts with TREM2 and observed the potential interaction in ALS patient tissues. Our data reveal the novel interaction between TREM2 and TDP-43, highlighting that TDP-43 is a potential ligand for microglial TREM2 and the interaction mediates neuroprotection of microglial TREM2 in TDP-43-related neurodegeneration.
Resilience and its Associated Factors in Head and Neck Cancer Patients in Pakistan: An Analytical Cross-Sectional Study
Authors: Zahid Nida , Zahid Wajeeha , Khalid Wardah , Azam Iqbal , Ikram Mubasher , Iftikar Haissan , Bhamani Shireen , Jabbar Adnan , Akhtar Shabbir , Siddiqui Moghira , Awan Mohammad , Asad Nargis , Ahmad Khabir 
Published: January 2021

Abstract
Introduction: The study aimed to assess resilience and its associated factors in head and neck cancer patients, post-treatment in a low middle income country (LMIC), Pakistan. Methods: An analytical cross-sectional study was conducted from November 2019 to May 2020 among head and neck cancer patients aged at least 18 years at the largest private tertiary care hospital, in Karachi, Pakistan. Information regarding resilience was collected through Wagnild and Young’s Resilience scale comprising of 14 items (RS-14). Depression and anxiety were assessed via Hospital Anxiety and Depression Scale (HADS) and social support by Enriched Social Support Instrument (ESSI). Results: The data was analyzed by linear regression modeling. Unadjusted and adjusted beta coefficients with 95% CI were reported. Total 250 head and neck cancer patients were recruited, 79% were males. Mean age of the patients was 51.59 years with 93% having high social support and only 8% having severe depression and 3% having severe anxiety. After adjusting for covariates in multivariable analysis lower resilience was associated with severe depression (-17 [-20.98,-12.93]) or borderline depression (-4[-8.41,-0.39]), severe anxiety (-11 [-17.88,-4.18]), low social support (-6 [-9.62,-1.71 ]), family members > 6 in the household (- 2[-4.31,-0.29), smokeless tobacco quitters post- treatment (10 [ 5.79, 14.45]), and those who underwent tracheotomy (-4 [-7.67,-0.21]). There was significant interaction between education and role in the family (decision maker). Conclusion: Resilience and social support is highly prevalent in our part of the world where collectivist culture prevails, thus resulting in low prevalence of depression and anxiety. High resilience score is reported among current smokeless tobacco users as compared to quitters post treatment. Tracheotomy and Large family size are inversely related to resilience. Formal education and decision making power in the household are mediators to resilience, demonstrating protective effect on mental health in head and neck cancer patients. Resilience-building interventions should be formulated to aid head and neck cancer patients to cope with the disease.
The Statistical Approach in Trial-based Economic Evaluations Matters: Get your Statistics Together!
Authors: Mutubuki Elizabeth , Alili Mohamed El , Bosmans Judith , Oosterhuis Teddy , Snoek Frank , Ostelo Raymond Ostelo , Tulder Maurits van , Dongen Johanna van 
Published: January 2021

Abstract
Background: Baseline imbalances, skewed costs, the correlation between costs and effects, and missing data are statistical challenges that are often not adequately accounted for in the analysis of cost-effectiveness data. This study aims to illustrate the impact of accounting for these statistical challenges in trial-based economic evaluations. Methods: Data from two trial-based economic evaluations, the REALISE and HypoAware studies, were used. In total, 14 full cost-effectiveness analyses were performed per study, in which the four statistical challenges in trial-based economic evaluations were taken into account step-by-step. Statistical approaches were compared in terms of the resulting cost and effect differences, ICERs, and probabilities of cost-effectiveness. Results: In the REALISE study and HypoAware study, the ICER ranged from 636,744€/QALY and 90,989€/QALY when ignoring all statistical challenges to -7,502€/QALY and 46,592€/QALY when accounting for all statistical challenges, respectively. The probabilities of the intervention being cost-effective at 0€/ QALY gained were 0.67 and 0.59 when ignoring all statistical challenges, and 0.54 and 0.27 when all of the statistical challenges were taken into account for the REALISE study and HypoAware study, respectively.Conclusions: Not accounting for baseline imbalances, skewed costs, correlated costs and effects, and missing data in trial-based economic evaluations may notably impact results. Therefore, when conducting trial-based economic evaluations, it is important to align the statistical approach with the identified statistical challenges in cost-effectiveness data. To facilitate researchers in handling statistical challenges in trial-based economic evaluations, software code is provided.
Experimental quantification of the impact of heterogeneous mix on thermonuclear burn
Authors: Albright Brian , Murphy Thomas , Douglas M , Cardenas T , Cooley James , Day Thomas , Denissen Nicolas , Stefano Carlos , Gore Robert , Gunderson M , Haack Jeffrey , Haines Brian , Hamilton Christopher , Kim Yongho , Lee M , Oertel J , Olson R , Randolph R , Shah R , Smidt J , Yin Lin 
Published: January 2021

Abstract
In inertial confinement fusion (ICF), deuterium-tritium (DT) fuel is brought to densities and temperatures where fusion ignition occurs. Mix of ablator material into the fuel may prevent ignition by diluting and cooling the fuel. MARBLE experiments at the National Ignition Facility (NIF) provide new insight into how mix affects thermonuclear burn. These experiments use laser-driven capsules containing deuterated plastic foam and tritium gas. Embedded within the foam are voids of known sizes and locations, which control the degree of heterogeneity of the fuel. Initially, the reactants are separated, with tritium concentrated in the voids and deuterium in the foam. During the implosion, mix occurs, leading to DT fusion reactions in the mixed region. Here we show that by measuring ratios of DT and deuterium-deuterium (DD) neutron yields for different macropore sizes and gas compositions, effects of mix heterogeneity on thermonuclear burn may be quantified and understood for the first time.
Dimer-monomer equilibrium of SARS-CoV-2 main protease as affected by small molecule inhibitors: a biophysical investigation
Authors: Silvestrini Lucia , Belhaj Norhan , Comez Lucia , Gerelli Yuri , Lauria Antonino , Libera Valeria , Mariani Paolo , Marzullo Paola , Ortore Maria , Piccionello Antonio Palumbo , Petrillo Caterina , Savini Lucrezia , Paciaroni Alessandro , Spinozzi Francesco 
Published: January 2021

Abstract
The maturation of coronavirus SARS-CoV-2, which is the etiological agent at the origin of the COVID-19 pandemic, requires a main protease Mpro to cleave the virus-encoded polyproteins. Despite a wealth of experimental information already available, there is wide disagreement about the Mpro monomer-dimer equilibrium dissociation constant. Since the functional unit of Mpro is a homodimer, the detailed knowledge of the thermodynamics of this equilibrium is a key piece of information for possible therapeutic intervention, with small molecules interfering with dimerization being potential broad-spectrum antiviral drug leads. In the present study, we exploit small angle x-ray scattering (SAXS) to investigate the structural features of the SARS-CoV-2 Mpro monomer-dimer equilibrium, by revealing the corresponding equilibrium dissociation constant and the associated thermodynamic parameters. SAXS is also used to study how the Mpro dissociation process is affected by small inhibitors selected through combinatorial design. Our results show that a clear picture connecting the ability of inhibitors to disrupt the Mpro dimerization with the loss of catalytic activity cannot be provided, thus highlighting the possible role of allosteric effects for the regulation of Mpro functionality.
Correlation between Job Satisfaction, Job Burnout and Turnover Intention of Surgical Nurses: A Cross-sectional Study in China
Authors: Zhong Yueping , Zhang Xiaomei , Wang Ya , Wei Rong , Cao Ling , Chen Xiaoyan , Hu Hanmei , Zhang Lei , Zhang Qun 
Published: January 2021

Abstract
Aim: To determine the correlation between job satisfaction, job burnout and turnover intention of surgical nurses.Background: Quite a number of studies have shown that there is a certain correlation between job satisfaction and job burnout of nurses, but researches on job satisfaction, job burnout and turnover intention of surgical nurses are relatively rare.Design: A descriptive correlational design was used in this study. Study participants were recruited from surgical nurses from Affiliated Hospital of Nantong University in Nantong, China. The main research method is questionnaire survey. The relationship between job satisfaction and job burnout and turnover intention of surgical nurses was analyzed by single factor analysis and correlation analysis.Results: A total of 506 participants was recruited from April to August 2020. The results show that there were significant differences in age and annual income of surgical nurses (P < 0.05). The job satisfaction level of surgical nurses was negatively correlated with emotional exhaustion of job burnout scale (r = -0.292, P < 0.05), negatively correlated with depersonalization (r = -0.424, P < 0.05), and negatively correlated with turnover intention (r = -0.375, P < 0.05).Conclusion: The findings indicate that the job satisfaction level of surgical nurses needs to be improved. Nursing managers should pay attention to the construction of hospital organization and culture, actively create supportive nursing work environment, strengthen the vocational training of junior nurses, further optimize the distribution of nursing human resources and welfare, reduce the job burnout and turnover rate of surgical nurses, and improve the job satisfaction of external nurses, so as to ultimately improve the quality of nursing.
TCF1 controls Treg functions that regulate inflammation, CD8 T-cell cytotoxicity, and severity of colon cancer
Authors: Khazaie Khashayarsha , Osman Abu , Yan Bingyu , Li Ying , Pavelko Kevin , Quandt Jasmin , Saadalla Abdulrahman , Rathore Mahendra , Kazemian Majid , Gounari Fotini 
Published: January 2021

Abstract
TCF1 is essential for the development and function of T regulatory cells (Tregs). However, how TCF1 regulates Treg function in homeostasis or under pathogenic conditions is poorly understood. Here, we ablated TCF1 in Tregs to elucidate its role in Treg specification in healthy mice and mice with colon cancer. RNAseq revealed that TCF1-deficient Tregs maintain their core transcriptional signature, but promote T-cell receptor, Tgfβ receptor, TH17, and Wnt/β-catenin signaling pathways. Single-cell RNAseq identified central-memory-Tregs with low Klf2 or high Mif expression, which upon downregulation of TCF1 gained TH17 characteristics and matured into Maf expressing effector Tregs. Tcf1-deficient Tregs exhibited enhanced suppression of T-cell proliferation and cytotoxicity but were compromised in controlling CD4+ T-cell polarization and inflammation. In mice with polyposis, Tcf1-deficient Tregs promoted inflammation and tumor growth. Thus, TCF1 differentially regulates Treg control of TH17 inflammation and T-cell cytotoxicity, and its action in Tregs determines colorectal cancer outcome.
The effects of naloxone, diazepam, and quercetin on seizure and sedation in acute on chronic tramadol administration: An experimental study
Authors: Nakhaee Samaneh , Farrokhfall Khadijeh , Miri-Moghaddam Ebrahim , Foadoddini Mohsen , Askari Masoumeh , Amirabadizadeh Alireza , Brent Jeffrey , Megarbane Bruno , Mehrpour omid 
Published: January 2021

Abstract
Background: Tramadol is a widely used synthetic opioid. Substantial research has previously focused on the neurological effects of this drug, while the efficacy of various treatments to reduce the associated side effects has not been well studied. This study aimed to evaluate the protective effects of naloxone, diazepam, and quercetin on tramadol induced seizure and sedation level in male rats. Methods: The project was performed with 72 male Wistar rats with an average weight of 200-250 g. The rats were randomly assigned to 8 groups. Tramadol was administered intraperitoneally at an initial dose of 25 mg/kg/day. On the 14th day, tramadol was injected at 75 mg/kg, either alone or together with naloxone, diazepam, and quercetin (acute and chronic) in different combinations. The rats were monitored for 6 hours on the last day, and the number, the duration, and the severity of seizures (using the criteria of Racine) were measured at different times. The sedation level was also assessed based on a 4-point criterion, ranging from 0 to 3, at different times after injection. Data were analyzed in SPSS software using Kruskal-Wallis, Chi-square, multivariate regression, and generalized estimating equation (GEE) tests. The significance level was set at P <0.05.Results: The naloxone-diazepam combination reduced the number of seizures, severity, and duration of seizures compared to the tramadol use alone and reduced the number of higher-intensity seizures to a greater extent than other treatments. Naloxone alone reduced the number and duration of seizures, as well as the duration of mild seizures. Diazepam decreased the severity and duration of seizures. However, it increased the number of mild seizures. In comparison with the tramadol alone group, the acute quercetin group had a lower duration of mild and severe seizures, and higher numbers of mild and moderate seizures. Chronic quercetin administration decreased the duration of seizures and significantly increased the number of mild seizures. Naloxone-Quercetin also reduced the duration of mild and severe seizures significantly. In the GEE model, all groups had higher sedation levels than the saline only group (P <0.001). None of the protocols had a significant effect on sedation levels compared to the other groups.Conclusion: The combined administration of naloxone and diazepam in acute on chronic tramadol poisoning can effectively reduce most seizure variables, compared to the tramadol use alone. However, none of the treatments can improve sedation levels.
Effectiveness of Paranasal Air Suction on Acute Migraine Using Portable Air Sucker – A Randomized, Double Blind Study
Authors: bandara SMR , samita S , kiridana AM , herath HMMTB 
Published: January 2021

Abstract
Background Migraine is a primary headache disorder and is the most common disabling primary headache disorder that occurs in children and adolescents. A recent study showed that paranasal air suction can provide relief to migraine headache. However, in order to get the maximum benefit out of it, an easy to use effective air sucker should be available. Aiming to fulfil the above requirement, a randomized, double blind control clinical trial was conducted to investigate the efficacy of a recently developed low–pressure portable air sucker.Methods Eighty-six Sri Lankan school children of age 16–19 years with migraine were used for the study. They were randomly allocated into two groups, and one group was subjected to six intermittent ten-second paranasal air suctions using the portable air sucker for 120 seconds. The other group was subjected to placebo air suction (no paranasal air suction). The effect of suction was the key concern but effect of side of headache, type of headache, and gender were also studied with respect to number of response variables. The key response studied was severity of headache. In addition, left and right supraorbital tenderness, photophobia, phonophobia, numbness over the face and scalp, nausea and generalized tiredness/weakness of the body were studied. The measurements on all those variables were made before and after suction, and the statistical analysis was performed based on before and after differences. As a follow–up, patients were monitored for 24-hour period.Results There was a significant reduction in the severity of headache and other migraine symptoms in the treatment group compared to the control group two minutes after the suction. These symptoms did not recur within 24-hour period and there were no significant side effects recorded during the 24-hour observation period.Conclusion This pilot study showed that low–pressure portable air sucker is effective in paranasal air suction, and suction for 120 seconds using the sucker can provide an immediate relief which can last for more than 24-hour period without any side effects.Trail registration Clinical Trial Government Identification Number – 1548/2016.
Application of The Robotic Seal PARO, A Neurological Biofeedback Medical Device, to Elderly Persons with Dementia at Home: An Analysis From Seven Cases
Authors: Inoue Kaoru , Yatsu Chiyomi , Yao Daryl Patrick , Sasaki Chihiro , Wada Kazuyoshi , Shibata Takanori 
Published: January 2021

Abstract
Background: In Japanese society today, many elderly persons with dementia (EPWD) are living at home. This research focused on the family members of EPWD who provide informal care and support. The purpose of this research was (1) to analyse the potential and effectiveness of care provided by the family with the use of the robotic seal PARO, a neurological biofeedback medical device, and (2) to identify and prioritise problems when utilising PARO in the home context. Methods: This study employed a mixed-methods approach involving observational data and interviews. Family members of seven households caring for EPWD were asked to use the seal robot “PARO” as a means to provide care. The family caregivers used PARO at home for more than three times per week, over one to three months. At the initial visit, an individualised purpose of PARO was established. Family members were taught how to operate PARO and how to facilitate PARO use. Research data were collected at initial and subsequent monthly visits, in the form of families’ observational feedback, interviews, and direct assessment of the subjects. Collected data were analysed quantitatively and qualitatively. Results: Five out of the seven elderly persons reacted positively to PARO and achieved their intervention goals. Acceptance of PARO use depended on the positive interaction observed at the initial encounter, which led to continued interest later on. On the other hand, for the subjects where “encouragement was required to trigger interaction” at the initial encounter, their subsequent interest may either increase or decrease. Furthermore, observed activities with PARO use for all families were conversations and physical touch to PARO. Some families facilitated reminiscence and intellectual activities. Conclusions: The study indicated that the effect of PARO application at home is possibly influenced by the participants' initial level of interest towards PARO. It is still crucial to perform careful observation and assessment of the benefit of PARO before adapting the treatment strategy. The families need specific advice from relevant healthcare professionals, such as occupational therapists, to maximise the use of PARO. This implies that effective robotic care at home requires professional support.
Mapping soil pollution risk from riparian land-cover changes in the headwater area of an inter-basin water diversion project
Authors: Wang Quanfang , Zhang Mengru , Zhang Yu , Yang Yuqi , Wang Xinsheng , Yang Lanfang , Chen Longyue , Xiao Ying 
Published: January 2021

Abstract
A novel scheme was proposed for mapping precise land-cover change in riparian zones and the resulted soil pollution risk of non-point source (NPS) from an inter-basin water diversion project on its headwater area. The scheme held three key points: 1) digital visualization of the riparian land-cover’s cyclical features was done using remote sensing data fusion of NDWI at high water level and NDVI and MNDWI at lower water level; 2) riparian zones were identified through color clustering on optimized RGB-fusion image that was picked out by applying Modified Vector-Angular Distance (MVAD) formula to measure difference between riparian and non-riparian zones in RGB space; 3) combining Export Coefficient Model (ECM) and the derived data on riparian land-cover change around Danjiangkou Reservoir in China, time-series loads of the soil NPS pollutants were estimated before and after the Middle Route of South-to-North Water Diversion Project (SNWDP) started running in 2014. The results indicated that risk of the potential soil pollution from land-cover change in the new riparian zones enlarged. Growth rates (GR) of total nitrogen (TN) and total phosphorus (TP) not only had significant spatial variation, but also were higher during initial running period of the SNWDP’s Middle Route.
The first record of exceptionally-preserved spiral coprolites from the Tsagan-Tsab Formation (Lower Cretaceous), Tatal, western Mongolia
Authors: Rummy Paul , Halaclar Kazim , Chen He 
Published: January 2021

Abstract
Seven coprolites from the Lower Cretaceous of Tsagan-Tsab formation have been described, thus making this paper a significant contribution to the study of the firstly recorded coprolites from the Mesozoic deposits in Mongolia. The collected coprolites comprised a total of five morphotypes, whereby six of them are considered to be spiral amphipolar and one as rod shape. CT scans have also revealed that all specimens showed various amounts of bony inclusions and fish scales of unknown affinity, hence deducing that the producers may have had a low acid digestive track and were unable to dissolve bone matters. Moreover, SEM-EDS analysis concluded its carnivorous nature. In addition, all coprolites exhibited bony elements of identical morphological structures, which indicated that the producers might have preyed on the same type of organism. Specimen IVPP V 27545 is the only non-spiral coprolite and the smallest compared to the rest and contain plant pollens, an infraorbital bone and clusters of bones of the prey; bioerosional scars are observed on the surface. We suggest that the spiral coprolites were produced by Asipenceriformes with ichthyophagous diet, while the non-spiral rod like coprolite might possibly belong to smaller vertebrate organisms that can’t be identified by us in this study.