bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Practical Guide to Rodent Islet Isolation and Assessment Revisited
Authors: Corbin Kathryn L. , West Hannah L. , Brodsky Samantha , Whitticar Nicholas B. , Koch William J. , Nunemaker Craig S. 
Published: March 2021

AbstractInsufficient insulin secretion is a key component of both type 1 and type 2 diabetes. Since insulin is released by the islets of Langerhans, obtaining viable and functional islets is critical for research and transplantation. The effective and efficient isolation of these small islands of endocrine cells from the sea of exocrine tissue that is the rest of the pancreas is not necessarily simple or quick. Choosing and administering the digestive enzyme, separation of the islets from acinar tissue, and culture of islets are all things that must be considered. The purpose of this review is to provide a history of the development of islet isolation procedures and to serve as a practical guide to rodent islet research for newcomers to islet biology. We discuss key elements of mouse islet isolation including choosing collagenase, the digestion process, purification of islets using a density gradient, and islet culture conditions. In addition, this paper reviews techniques for assessing islet viability and function such as visual assessment, glucose-stimulated insulin secretion and intracellular calcium measurements. A detailed protocol is provided that describes a common method our laboratory uses to obtain viable and functional mouse islets for in vitro study. This review thus provides a strong foundation for successful procurement and purification of high-quality mouse islets for research purposes.
Clinical characteristics and treatment outcomes of acute severe autoimmune hepatitis
Authors: Zheng Linhua , Liu Yansheng , Shang Yulong , Han Zheyi , Han Ying 
Published: March 2021

Abstract
Background and aim
Acute severe autoimmune hepatitis (AS-AIH) is a rare cause of acute liver failure (ALF), which is often neglected and delayed in treatment. The purpose of this study was to analyze the clinical characteristics and therapeutic effects of AS-AIH.

Methods
Retrospective analysis was performed. AIH was diagnosed according to the International Autoimmune Hepatitis Group (IAIHG) criteria revised in 1999. AS-AIH was defined as an acute presentation (onset of symptoms to presentation of ≤ 26 weeks) and INR of ≥ 1.5, and no histologic evidence of cirrhosis.

Results
Twelve patients were diagnosed as AS-AIH. At baseline, median immunoglobulin G was 28.35 g/L (range, 11.4–49.2). Ten (83.3%) patients were antinuclear antibodies and/or anti-smooth muscle antibodies positive. The prominent histologic characteristics were lobular necrosis/inflammation (91.7%) and plasma cell infiltration (100%). All patients received corticosteroid therapy. Death occurred in 2 (16.7%) patients within 30 days resulted from ALF. The average interval between the onset of symptoms and initiation of corticosteroid therapy in deceased patients was 65 days, compared with 19 days for survivors.

Conclusions
AS-AIH is an uncommon disease with poor outcomes. Patients with acute severe hepatitis of unknown cause should be minded the possibility of AS-AIH and corticosteroids should be considered as soon as possible.
Physiotherapy in nursing homes. A qualitative study of physiotherapists’ views and experiences
Authors: Sterke Shanty , Nascimento da Cunha Ana Paula , Oomen Hanneke , Voogt Lennard , Goumans Marleen 
Published: March 2021

AbstractBackgroundThere are distinct differences in the implementation of physiotherapeutic care in nursing homes. Both nationally and internationally staffing levels of physiotherapy differ significantly between and within nursing homes. Since legislation or guidelines that specify the parameters of physiotherapy required in nursing homes are lacking, it is unknown how physiotherapists currently estimate the usefulness and necessity of physiotherapy in individual situations in long-term care. The purpose of this study was to describe how physiotherapists actually work, and how they want to work, in daily practice in Dutch nursing homes.MethodsWe performed a qualitative study with an online questionnaire. We asked 72 physiotherapists working in Dutch nursing homes to describe as accurately as possible usual care in nine different cases in long-term care. Furthermore we asked them to describe their role in the prevention and treatment of a number of indicators that measure the quality of care in nursing homes. Two reviewers thematically analysed the answers to the questionnaires.ResultsForty-six physiotherapists returned the questionnaire. Physiotherapy services include active exercise therapy aimed to improve mobility and movement dysfunctions, advising on prevention and management of falls, pressure ulcers, incontinence, malnutrition and sarcopenia, overweight, physical restraints, intertrigo, chronic wounds, behavioural and psychological symptoms in dementia, and physical inactivity, and ergonomic and behavioural training. The way and extent in which physiotherapists are involved in the various care- and functional problems differs and depends on organisational and personal factors such as, organisation’s policy, type of ward, time pressure, staffing level, collaboration with other members of the multidisciplinary team, or lack of knowledge.ConclusionPhysiotherapists in nursing homes are involved in the prevention and management of different care situations and functional problems. The way in which they are involved differs between physiotherapist. Aiming for more uniformity seems necessary. A shared vision can help physiotherapists to work more consistently and will strengthen their position in nursing homes.
Manufacturing and banking canine adipose-derived mesenchymal stem cells for veterinary clinical application
Authors: Luo Huina , Li Dongsheng , Chen Zhisheng , Wang Bingyun , Chen Shengfeng 
Published: March 2021

Abstract
Background
Mesenchymal stem cells (MSCs) have generated a great amount of interest in recent years as a novel therapeutic application for improving the quality of pet life and helping them free from painful conditions and diseases. It has now become critical to address the challenges related to the safety and efficacy of MSCs expanded in vitro. In this study, we establish a standardized process for manufacture of canine adipose-derived MSCs (AD-MSCs), including tissue sourcing, cell isolation and culture, cryopreservation, thawing and expansion, quality control and testing, and evaluate the safety and efficacy of those cells for clinical applications.

Results
After expansion, the viability of AD-MSCs manufactured under our standardized process was above 90 %. Expression of surface markers and differentiation potential was consistent with ISCT standards. Sterility, mycoplasma, and endotoxin tests were consistently negative. AD-MSCs presented normal karyotype, and did not form in vivo tumors. No adverse events were noted in the case treated with intravenously AD-MSCs.

Conclusions
Herein we demonstrated the establishment of a feasible bioprocess for manufacturing and banking canine AD-MSCs for veterinary clinical use.
Beyond national indicators: adapting the Demographic and Health Surveys’ sampling strategies and questions to better inform subnational malaria intervention policy
Authors: Ozodiegwu Ifeoma D. , Ambrose Monique , Battle Katherine E. , Bever Caitlin , Diallo Ousmane , Galatas Beatriz , Runge Manuela , Gerardin Jaline 
Published: March 2021

AbstractIn malaria-endemic countries, prioritizing intervention deployment to areas that need the most attention is crucial to ensure continued progress. Global and national policy makers increasingly rely on epidemiological data and mathematical modelling to help optimize health decisions at the sub-national level. The Demographic and Health Surveys (DHS) Program is a critical data source for understanding subnational malaria prevalence and intervention coverage, which are used for parameterizing country-specific models of malaria transmission. However, data to estimate indicators at finer resolutions are limited, and surveys questions have a narrow scope. Examples from the Nigeria DHS are used to highlight gaps in the current survey design. Proposals are then made for additional questions and expansions to the DHS and Malaria Indicator Survey sampling strategy that would advance the data analyses and modelled estimates that inform national policy recommendations. Collaboration between the DHS Program, national malaria control programmes, the malaria modelling community, and funders is needed to address the highlighted data challenges.
Identification of tumor antigens and immune subtypes of pancreatic adenocarcinoma for mRNA vaccine development
Authors: Huang Xing , Zhang Gang , Tang Tianyu , Liang Tingbo 
Published: March 2021

Abstract
Background
Although mRNA vaccines have been effective against multiple cancers, their efficacy against pancreatic adenocarcinoma (PAAD) remains undefined. Accumulating evidence suggests that immunotyping can indicate the comprehensive immune status in tumors and their immune microenvironment, which is closely associated with therapeutic response and vaccination potential. The aim of this study was to identify potent antigens in PAAD for mRNA vaccine development, and further distinguish immune subtypes of PAAD to construct an immune landscape for selecting suitable patients for vaccination.

Methods
Gene expression profiles and clinical information of 239 PAAD datasets were extracted from ICGC, and RNA-Seq data of 103 samples were retrieved from TCGA. GEPIA was used to calculate differential expression levels and prognostic indices, cBioPortal program was used to compare genetic alterations, and TIMER was used to explore correlation between genes and immune infiltrating cells. Consensus cluster was used for consistency matrix construction and data clustering, DAVID was used for functional annotation, and graph learning-based dimensional reduction was used to depict immune landscape.

Results
Six overexpressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in PAAD, including ADAM9, EFNB2, MET, TMOD3, TPX2, and WNT7A. Furthermore, five immune subtypes (IS1-IS5) and nine immune gene modules of PAAD were identified that were consistent in both patient cohorts. The immune subtypes showed distinct molecular, cellular and clinical characteristics. IS1 and IS2 exhibited immune-activated phenotypes and correlated to better survival compared to the other subtypes. IS4 and IS5 tumors were immunologically cold and associated with higher tumor mutation burden. Immunogenic cell death modulators, immune checkpoints, and CA125 and CA199, were also differentially expressed among the five immune subtypes. Finally, the immune landscape of PAAD showed a high degree of heterogeneity between individual patients.

Conclusions
ADAM9, EFNB2, MET, TMOD3, TPX2, and WNT7A are potent antigens for developing anti-PAAD mRNA vaccine, and patients with IS4 and IS5 tumors are suitable for vaccination.
Fabrication of monodisperse magnetic nanorods for improving hyperthermia efficacy
Authors: Zhao Shan , Hao Nanjing , Zhang John X. J. , Hoopes P. Jack , Shubitidze Fridon , Chen Zi 
Published: March 2021

Abstract
Background
Hyperthermia is one of the promising cancer treatment strategies enabled by local heating with the use of tumor-targeting magnetic nanoparticles (MNP) under a non-invasive magnetic field. However, one of the remaining challenges is how to achieve therapeutic levels of heat (without causing damages to regular tissues) in tumors that cannot be effectively treated with anti-tumor drug delivery.

Results
In this work, we report a facile method to fabricate magnetic nanorods for hyperthermia by one-step wet chemistry synthesis using 3-Aminopropyltrimethoxysilane (APTMS) as the shape-controlling agent and ferric and ferrous ions as precursors. By adjusting the concentration of APTMS, hydrothermal reaction time, ratios of ferric to ferrous ions, magnetic nanorods with aspect ratios ranging from 4.4 to 7.6 have been produced. At the clinically recommended field strength of 300 Oe (or less) and the frequency of 184 kHz, the specific absorption rate (SAR) of these nanorods is approximately 50 % higher than that of commercial Bionized NanoFerrite particles.

Conclusions
This increase in SAR, especially at low field strengths, is crucial for treating deep tumors, such as pancreatic and rectal cancers, by avoiding the generation of harmful eddy current heating in normal tissues.
Sexual function, mental health, and quality of life under strain of COVID-19 pandemic in Iranian pregnant and lactating women: a comparative cross-sectional study
Authors: Mirzaei Negin , Jahanian Sadatmahalleh Shahideh , Bahri Khomami Mahnaz , Moini Ashraf , Kazemnejad Anoshirvan 
Published: March 2021

Abstract
Background
The impact of COVID-19 pandemic on mental health of pregnant and lactating women is unclear. This study aimed to assess the impact of COVID-19 on psychological health, sexual function, and quality of life (QoL) in Iranian pregnant and lactating women and compare the results with non-pregnant/non-lactating women.

Method
This comparative cross-sectional study was carried out on pregnant and lactating women, with non-pregnant/non-lactating women from May to Jun 2020. Patients were asked to complete three questionnaires: Hospital Anxiety and Depression Scale (HADS), Female Sexual Function Index (FSFI), and Short-Form Health Survey (SF-12). One-way ANOVA was used to reveal the statistical differences between the three groups.

Result
The mean age of patients was 20.81 ± 5.92 years old. The mean (SD) score of HADS in pregnant, lactating and non-pregnant / non-lactating women were 12.11 (6.72), 11.98 (8.44) and 9.38 (6.2) respectively, and the results showed that the scores in pregnant, lactating women were higher than non-pregnant / non-lactating women (P < 0.001). Also the mean (SD) score of QOL and FSFI was 68.29 (9.47), 74.18 (12.65), 79.03 (10.48) and 22.71 (8.16), 22.72 (8.16), 26.19 (3.93) in three groups and the scores in pregnant, lactating women were lower than non-pregnant/non-lactating women (P < 0.001).

Conclusion
The COVID-19 epidemic increases the risk of depression, anxiety, FSD, and lowers QoL in pregnant and lactating women, with the general population. This suggests the urgent need for psychological intervention in the maternal population during the epidemic.
Reconciling ACEA and MCDA: is there a way forward for measuring cost-effectiveness in the U.S. healthcare setting?
Authors: Zamora Bernarda , Garrison Louis P. , Unuigbe Aig , Towse Adrian 
Published: March 2021

Abstract
Background
The ISPOR Special Task Force (STF) on US Value Assessment Frameworks was agnostic about exactly how to implement the quality-adjusted life year (QALY) as a key element in an overall cost-effectiveness evaluation. But the STF recommended using the cost-per-QALY gained as a starting point in deliberations about including a new technology in a health plan benefit. The STF offered two major alternative approaches—augmented cost-effectiveness analysis (ACEA) and multi-criteria decision analysis (MCDA)—while emphasizing the need to apply either a willingness-to-pay (WTP) or opportunity cost threshold rule to operationalize the inclusion decision.

Methods
The MCDA model uses the multi-attribute utility function. The ACEA model is based on the expected utility theory. In both ACEA and MCDA models, value trade-offs are derived in a hierarchical model with two high-level objectives which measure overall health gain separately from financial attributes affecting consumption.

Results
Even though value trade-offs can be elicited or revealed without considering budget constraints, we demonstrate that they can be used similarly to WTP-based cost-effectiveness thresholds for resource allocation decisions. The consideration of how costs of medical technology, income, and severity of disease affect value trade-offs demonstrates, however, that reconciling decisions in ACEA and MCDA requires that health and consumption are either complements or independent attributes.

Conclusions
We conclude that value trade-offs derived either from ACEA or MCDA move similarly with changes in main factors considered by enrollees and decision makers—costs of the medical technology, income, and severity of disease. Consequently, this complementarity between health and consumption is a necessary condition for reconciling ACEA and MCDA. Moreover, their similarity would be further enhanced if the QALY is used as the key attribute or anchor in the MCDA value function: the choice between the two is a pragmatic question that is still open.
Aberrant regulation of retinoic acid signaling genes in cerebral arterio venous malformation nidus and neighboring astrocytes
Authors: Thomas Jaya Mary , Sasankan Dhakshmi , Surendran Sumi , Abraham Mathew , Rajavelu Arumugam , Kartha Chandrasekharan C. 
Published: March 2021

Abstract
Background
Cerebral arterio venous malformations (AVM) are a major causal factor for intracranial hemorrhage, which result in permanent disability or death. The molecular mechanisms of AVM are complex, and their pathogenesis remains an enigma. Current research on cerebral AVM is focused on characterizing the molecular features of AVM nidus to elucidate the aberrant signaling pathways. The initial stimuli that lead to the development of AVM nidus structures between a dilated artery and a vein are however not known.

Methods
In order to understand the molecular basis of development of cerebral AVM, we used in-depth RNA sequencing with the total RNA isolated from cerebral AVM nidus. Immunoblot and qRT-PCR assays were used to study the differential gene expression in AVM nidus, and immunofluorescence staining was used to study the expression pattern of aberrant proteins in AVM nidus and control tissues. Immunohistochemistry was used to study the expression pattern of aberrant proteins in AVM nidus and control tissues.

Results
The transcriptome study has identified 38 differentially expressed genes in cerebral AVM nidus, of which 35 genes were upregulated and 3 genes were downregulated. A final modular analysis identified an upregulation of ALDH1A2, a key rate-limiting enzyme of retinoic acid signaling pathway. Further analysis revealed that CYR61, a regulator of angiogenesis, and the target gene for retinoic acid signaling is upregulated in AVM nidus. We observed that astrocytes associated with AVM nidus are abnormal with increased expression of GFAP and Vimentin. Triple immunofluorescence staining of the AVM nidus revealed that CYR61 was also overexpressed in the abnormal astrocytes associated with AVM tissue.

Conclusion
Using high-throughput RNA sequencing analysis and immunostaining, we report deregulated expression of retinoic acid signaling genes in AVM nidus and its associated astrocytes and speculate that this might trigger the abnormal angiogenesis and the development of cerebral AVM in humans.
The psychoactive drug of abuse mephedrone differentially disrupts blood-brain barrier properties
Authors: Buzhdygan Tetyana P. , Rodrigues Cassidy R. , McGary Hannah M. , Khan Jana A. , Andrews Allison M. , Rawls Scott M. , Ramirez Servio H. 
Published: March 2021

AbstractBackgroundSynthetic cathinones are a category of psychostimulants belonging to the growing number of designer drugs also known as “Novel Psychoactive Substances” (NPS). In recent years, NPS have gained popularity in the recreational drug market due to their amphetamine-like stimulant effects, low cost, ease of availability, and lack of detection by conventional toxicology screening. All these factors have led to an increase in NPS substance abuse among the young adults, followed by spike of overdose-related fatalities and adverse effects, severe neurotoxicity, and cerebral vascular complications. Much remains unknown about how synthetic cathinones negatively affect the CNS and the status of the blood-brain barrier (BBB).MethodsWe used in vitro models of the BBB and primary human brain microvascular endothelial cells (hBMVEC) to investigate the effects of the synthetic cathinone, 4-methyl methcathinone (mephedrone), on BBB properties.ResultsWe showed that mephedrone exposure resulted in the loss of barrier properties and endothelial dysfunction of primary hBMVEC. Increased permeability and decreased transendothelial electrical resistance of the endothelial barrier were attributed to changes in key proteins involved in the tight junction formation. Elevated expression of matrix metalloproteinases, angiogenic growth factors, and inflammatory cytokines can be explained by TLR-4-dependent activation of NF-κB signaling.ConclusionsIn this first characterization of the effects of a synthetic cathinone on human brain endothelial cells, it appears clear that mephedrone-induced damage of the BBB is not limited by the disruption of the barrier properties but also include endothelial activation and inflammation. This may especially be important in comorbid situations of mephedrone abuse and HIV-1 infections. In this context, mephedrone could negatively affect HIV-1 neuroinvasion and NeuroAIDS progression.
Pretibial myxedema in a euthyroid patient: a case report
Authors: Ambachew Rediet , Yosef Tizita , Gebremariam Aklilu M. , Demere Lishan , Aberra Theodros , Tarekegn Getahun , Reja Ahmed 
Published: March 2021

Abstract
Background
Pretibial myxedema also known as localized myxedema, thyroid dermopathy, or infiltrative dermopathy and rarely as localized mucinosis is an infrequent manifestation of Graves’ disease. It can appear before, during, or after the thyrotoxic state. Euthyroid pretibial myxedema is a rare presentation with few case reports in the literature. This case highlights the importance of considering pretibial myxedema when characteristic skin lesions are observed in a euthyroid patient.

Case presentation
A 72-year old male Ethiopian patient with a very rare presentation of biopsy-proven pretibial myxedema in a euthyroid state without history of thyroid disease and absence of thyroid autoimmune markers. Resolution of skin lesion was achieved after topical corticosteroid application.

Conclusion
Absence of history of thyroid disorder and normal thyroid function tests should not exclude the diagnosis of pretibial myxedema.