bluuebunny/crossref_metadata_2025_split huggingface dataset:
Losartan treatment attenuates hindlimb unloading-induced atrophy in the soleus muscle of female rats via canonical TGF-β signaling
Authors: Yoshihara Toshinori , Takaragawa Mizuki , Dobashi Shohei , Naito Hisashi 
Published: March 2022

AbstractWe investigated the protective effect of losartan, an angiotensin II type 1 receptor blocker, on soleus muscle atrophy. Age-matched male and female Wistar rats were subjected to hindlimb unloading, and the soleus muscle was removed on days 1 and 7 for analysis. Females showed greater reductions in relative weight and myofiber cross-sectional area of the soleus muscle than males on day 7 post-hindlimb unloading. Losartan partially protected females against muscle atrophy. Activation of the canonical TGF-β signaling pathway, assessed via Smad2/3 phosphorylation, was lower in females following losartan treatment and associated with lower levels of protein ubiquitination after 1 (myofibril) and 7 (cytosol) days of unloading. However, no effect was observed in non-canonical TGF-β signaling (p44/p42 and p38 MAPK phosphorylation) in males or females during unloading. Our results suggest that losartan provides partial protection against hindlimb unloading-induced soleus muscle atrophy in female rats, possibly associated with decreased canonical TGF-β signaling.
Cardiovascular disturbances in COVID-19: an updated review of the pathophysiology and clinical evidence of cardiovascular damage induced by SARS-CoV-2
Authors: Lawal Ismaheel O. , Kgatle Mankgopo M. , Mokoala Kgomotso , Farate Abubakar , Sathekge Mike M. 
Published: March 2022

AbstractSevere acute respiratory coronavirus-2 (SARS-Co-2) is the causative agent of coronavirus disease-2019 (COVID-19). COVID-19 is a disease with highly variable phenotypes, being asymptomatic in most patients. In symptomatic patients, disease manifestation is variable, ranging from mild disease to severe and critical illness requiring treatment in the intensive care unit. The presence of underlying cardiovascular morbidities was identified early in the evolution of the disease to be a critical determinant of the severe disease phenotype. SARS-CoV-2, though a primarily respiratory virus, also causes severe damage to the cardiovascular system, contributing significantly to morbidity and mortality seen in COVID-19. Evidence on the impact of cardiovascular disorders in disease manifestation and outcome of treatment is rapidly emerging. The cardiovascular system expresses the angiotensin-converting enzyme-2, the receptor used by SARS-CoV-2 for binding, making it vulnerable to infection by the virus. Systemic perturbations including the so-called cytokine storm also impact on the normal functioning of the cardiovascular system. Imaging plays a prominent role not only in the detection of cardiovascular damage induced by SARS-CoV-2 infection but in the follow-up of patients’ clinical progress while on treatment and in identifying long-term sequelae of the disease.
Clinicians’ perceptions of barriers to cervical cancer screening for women living with behavioral health conditions: a focus group study
Authors: Mkuu Rahma S. , Staras Stephanie A. , Szurek Sarah M. , D’Ingeo Dalila , Gerend Mary A. , Goede Dianne L. , Shenkman Elizabeth A. 
Published: March 2022

Abstract
Background
Women with behavioral health (BH) conditions (e.g., mental illness and substance abuse) receive fewer cervical cancer (CC) screenings, are diagnosed at more advanced cancer stages, and are less likely to receive specialized treatments. The aim of this study was to identify barriers that healthcare providers face in providing CC screening to women with BH conditions.

Methods
Guided by the Consolidated Framework for Implementation Research, we conducted four focus groups in North Florida with 26 primary care and BH clinicians and staff to examine perceived barriers to CC screening among their patients with BH conditions to guide the future development of a tailored cervical cancer screening and follow-up intervention. Thematic analysis was used to analyze verbatim transcripts from audiotaped focus groups.

Results
Three main themes of barriers emerged from the data: 1) BH conditions related barriers included a history of trauma, stigma and discrimination, and uncontrolled comorbid conditions, 2) System level barriers related to lack of integration between BH and primary care, and 3) Similar barriers to the general population including lack of health insurance, insufficient processes to send out reminders, and challenges with communicating with patients.

Conclusions
Tailored CC screening interventions that address the unique needs of women with BH conditions are needed. Strategies that address improving trust between patients and healthcare providers, identifying avenues to improve receipt of screening during time-limited clinical visits, connecting BH and primary care providers, and addressing the social determinants of health have potential to improve CC screening rates for women with BH conditions.
Glycemic variability assessed by continuous glucose monitoring in hospitalized patients with community-acquired pneumonia
Authors: Olsen Mikkel Thor , Dungu Arnold Matovu , Klarskov Carina Kirstine , Jensen Andreas Kryger , Lindegaard Birgitte , Kristensen Peter Lommer 
Published: March 2022

Abstract
Background
Glycemic variability (GV) has only been sparsely studied in patients with community-acquired pneumonia (CAP). This study aimed to quantify in-hospital GV in CAP patients, including determining the impact of type 2 diabetes mellitus (T2DM) and glucocorticoid (GC) treatment on GV.

Methods
This is a prospective cohort study of CAP patients (N = 40) with or without T2DM and treated or not with GCs. The primary endpoint was GV measured as glucose standard deviation (SD), coefficient of variation (CV), and postprandial glucose excursions (PPGE) based on continuous glucose monitoring (CGM). Analysis of glucose data was split into daytime and nighttime when possible.

Results
Patients included had a mean age of 74 (range 55 to 91) years. SD (95%CI) increased by a factor of 1.93 (1.40 to 2.66) and 2.29 (1.38 to 3.81) in patients with T2DM and not treated with GCs during the daytime and the nighttime, respectively (both P < 0.01), and by a factor of 1.42 (1.04 to 1.97) in patients treated with GCs but without T2DM during the daytime (P = 0.031) compared to patients without T2DM and not treated with GCs. CV (95%CI) increased by 5.1 (0.0 to 10.1) and 8.1 (1.0 to 15.2) percentage points during the daytime and the nighttime, respectively, in patients with T2DM and not treated with GCs compared to patients without T2DM and not treated with GCs (P = 0.046 and P = 0.026, respectively). PPGE (95% CI) increased during lunch by 2.5 (0.7 to 4.3) mmol/L (45 (13 to 77) mg/dL) in patients with T2DM and treated with GCs compared to patients without T2DM and not treated with GCs (P = 0.018).

Conclusions
CAP patients receiving GCs, especially those with T2DM, are at great risk of developing high GV and therefore require clinical attention to mitigate GV. This applies particularly during the daytime. Results support the 1 to 2-h post-lunch screening procedure for glucocorticoid-induced hyperglycemia in patients without diabetes. SD was positively correlated with hospital length of stay.
Cytotoxic effects of different detergent containing children's toothpastes on human gingival epithelial cells
Authors: Birant Sinem , Duran Yazgul , Akkoc Tunc , Seymen Figen 
Published: March 2022

Abstract
Background
This study aimed to evaluate possible cytotoxic effects to gingival epithelial cells exposed to children toothpastes containing different detergent.

Methods
Tissues required for the isolation of human gingival epithelial cells were obtained by biopsy during the extraction of the impacted third molar tooth. Toothpaste solutions of different concentrations were prepared from five different children’s toothpastes with different detergent contents. Isolated gingival epithelial cells were stimulated with experimental groups consisting of toothpaste solutions (Colgate, Sensodyne, Splat, Nenedent, Perlodent) at different concentrations and a control group consisting of complete Dulbecco’s modified eagle medium. After the experiments, cell viability was evaluated using flow cytometry. 2 Way ANOVA was used to see the interaction effect of the main effects of toothpaste solution and concentration factors. Pairwise comparisons were made by Tukey post hoc tests. In the study, the significance level was taken as 0.05.

Results
As a result of the analysis, it was seen that the toothpaste solution and concentration factors and the interactions of these 2 factors were effective on the viable, early apoptotic, late apoptotic and necrotic cell rates. The statistically highest live cell ratios were detected in Splat’s toothpaste solutions (90.14% at 0.4% concentration) after the control group (90.82%) and the group with the lowest viability values was determined in Colgate group (75.74% at 0.4% concentration) (p < 0.05).

Conclusions
According to the results of the study, it was observed that toothpastes containing SLS affected the viability of cells more negatively than toothpastes with other detergent contents.
A scoping review of the evidence for community-based dementia palliative care services and their related service activities
Authors: O’Connor Niamh , Fox Siobhan , Kernohan W George , Drennan Jonathan , Guerin Suzanne , Murphy Aileen , Timmons Suzanne 
Published: March 2022

AbstractBackgroundPalliative care is identified internationally as a priority for efficacious dementia care. Research into “effective models” of palliative care for people with dementia has been recommended by several European countries. To build an effective service-delivery model we must gain an understanding of existing models used in similar settings. The study aim is to identify core components of extant models of palliative care for people with dementia, and their families, who are living at home in the community.MethodsA scoping review was employed. The search strategy was devised to identify all peer-reviewed research papers relating to the above aim. This process was iterative, and the search strategy was refined as evidence emerged and was reviewed. All types of study designs and both quantitative and qualitative studies of non-pharmacological interventions were considered for inclusion.ResultsThe search identified 2,754 unique citations, of which 18 papers were deemed eligible for inclusion. Although a palliative care approach is recommended from early in the disease process, most evidence involves end-of-life care or advanced dementia and pertains to residential care. The majority of the research reviewed focused on the effects of advance care planning, and end-of-life care; specialist palliative care input, and/or generalist palliative care provided by dementia services to enable people to remain at home and to reduce costs of care. Community staff training in palliative care appeared to improve engagement with Specialist Palliative Care teams. Integration of dementia and palliative care services was found to improve care received for people with dementia and their carers.ConclusionsWhile the evidence for integration of dementia and palliative care services is promising, further high-quality research is necessary particularly to identify the key components of palliative care for people living with dementia. This is imperative to enable people with dementia to inform their own care, to stay living at home for as long as possible, and, where appropriate, to die at home.
Health related quality of life among pregnant women living with HIV in Kenya, results from comparing a patient generated index and the Euroqol 5 dimension 3 level
Authors: Mwangi Jonathan , Ternent Laura , Ujiji Patricia Opondo Awiti , Were Edwin , Ekström Anna Mia 
Published: March 2022

Abstract
Background
Standardized tools are used to measure health-related quality of life (HRQoL) and they focus on selected physical, emotional, and social functioning. This approach may miss out on the heterogeneity of HRQoL among various sub-populations. The patient-generated index (PGI) is a tool used to measure HRQoL based on patients' expectations. Among patients living with HIV, HRQoL is an important indicator as the world moves beyond the UNAIDS 90-90-90 goals, towards the so-called fourth 90 that aims at good HRQoL. We compared the PGI and the Euroqol 5 Dimension 3-level (EQ-5D-3L) to identify areas of importance to pregnant women living with HIV affecting thier HRQoL.

Methods
Through convenience sampling, we surveyed 100 pregnant women living with HIV attending antenatal and postnatal clinics in Western Kenya, using both the PGI and the EQ-5D-3L questionnaires. A PGI score and EQ-5D-3L index were generated for each participant. Data from the PGI was also summarized into themes. The PGI scores and EQ-5D-3L index scores were correlated using Pearson correlation.

Results
From the PGI tool, 64% of the women reported having two to three main priority areas of their lives affected by their HIV status. These areas centered on themes of economic wellbeing (84% of the women), physical health (58%), psychological/emotional health (49%), and relationships (28%). The mean PGI score was 2.01 [SD = 1.10; median 1.10]. The majority of the women reported having no problems in any of the 5 dimensions captured in the EQ-5D-3L. The mean EQ-5D-3L score was 0.94 [SD = 1.10; median 1.00]. Both the EQ-5D-3L and the PGI showed less than perfect HRQoL. There was no correlation between the PGI and the EQ-5D-3L scores.

Conclusion
The PGI may capture aspects of contextual social and emotional life for Kenyan pregnant women living with HIV that are not identified by generic tools. Highlighting areas of importance to patients’ HRQoL is key as focus shifts towards the fourth 90 and may also inform the design of care programs aligned to patient needs.
A week long “pep” talk – initial and 2–3-year longitudinal data on the Ottawa Psychiatry Enrichment Program (OPEP)
Authors: Lee Elliott Kyung , Morra Alexandra , Bazaid Khalid , Bezzahou Abdellah , Simas Kevin , Taplin Christopher , Chun Soojin , Fiedorowicz Jess G. , Douglass Alan Bruce 
Published: March 2022

Abstract
Background
Recruitment to psychiatry as a career has been challenging in Canada and abroad despite the known shortage and increasing burden of psychiatric issues globally. Deterrents to choosing psychiatry as a career include its negative stigma and paucity of knowledge about the field. The study goal was to evaluate the Ottawa Psychiatry Enrichment Program (OPEP), a one-week extracurricular program about psychiatry as a career for 1st and 2nd year medical students. We hypothesized OPEP would improve students’ attitudes towards psychiatry, and positive changes would be sustained 2–3 years later following their residency match. We hypothesized there would be a high recruitment of OPEP attendees to psychiatry programs.

Methods
1st and 2nd year medical students from Canada applied to OPEP. Attendees completed the Attitudes Towards Psychiatry Questionnaire (ATP-30) at three times: before OPEP (PreOPEP), after OPEP (PostOPEP) and after their Canadian Residency Matching Service (CaRMs) match 2–3 years later. OPEP ATP-30 scores were compared to third-year student ATP-30 scores before and after their psychiatry rotation. Data were analysed using Friedman non-parametric ANOVA and post hoc testing by either Wilcoxon rank sum test, Wilcoxon matched pairs signed rank test, or parametric Welch independent t-test as appropriate. Effect sizes of group mean differences were calculated using Cohen’s “d”.

Results
Between 2017–2018, 29/53 Canadian applicants were selected for OPEP. 100%, 93.1% and 75.8% of OPEP students completed the PreOPEP, PostOPEP, and CaRMs ATP-30 surveys respectively. 43% of OPEP attendees matched to psychiatry. PostOPEP ATP-30 scores (mean = 133, median = 137, SD = 10.6) were significantly higher than PreOPEP ATP-30 (mean score = 121, median = 122, SD = 9.3, p < 0.001) and CaRMS ATP-30 (mean = 126, median = 127, SD = 12.3, p < 0.02) scores. OPEP effect size on ATP-30 scores was large (d = 1.2) but decreased 2–3 years later (p = 0.078, d = 0.44). 97/202 students completed the ATP-30 before and after their psychiatry rotation (clerkship). Clerkship effect size on improvement in ATP-30 was moderate (d = 0.39). There was a non-significant difference between OPEP CaRMS ATP-30 and post clerkship ATP-30 scores (median 127 vs 121, p = 0.056).

Conclusions
OPEP ameliorated attitudes toward Psychiatry, but improvement deteriorated longitudinally. Strategies for program design, and innovations to boost/retain improvements during clerkship years are discussed.
BET proteins are essential for the specification and maintenance of the epiblast lineage in mouse preimplantation embryos
Authors: Tsume-Kajioka Mami , Kimura-Yoshida Chiharu , Mochida Kyoko , Ueda Yoko , Matsuo Isao 
Published: March 2022

AbstractBackgroundDuring mammalian preimplantation development, as the fertilized egg develops and differentiates, three cell lineages become specified: trophectoderm (TE), epiblast, and primitive endoderm (PrE). Through two steps of cell fate decisions, 16-cell blastomeres develop into TE and an inner cell mass (ICM), and thereafter, the latter differentiates into pluripotent epiblast and PrE. Although bromodomain and extra-terminal domain (BET) proteins, such as BRD4, are necessary for the transcriptional activation of genes involved in the maintenance of mouse embryonic stem cells by occupying their enhancers, their roles in the development of mouse preimplantation are unknown.ResultsTo evaluate the effect of BET protein deficiency on cell lineage formation, we cultured preimplantation embryos in the presence of JQ1, which blocks the binding of BET bromodomains to acetylated-histones. We found BET inhibition blocked the transcriptional activation of genes, such asNanog,Otx2, andSox2, important for the formation of the epiblast lineage in blastocysts. Expression studies with lineage-specific markers in morulae and blastocysts revealed BET proteins were essential for the specification and maintenance of the epiblast lineage but were dispensable for the formation of primarily extraembryonic TE and PrE lineages. Additional Ingenuity Pathway Analysis and expression studies with a transcriptionally active form of signal transducer and activator of the transcription 3 (STAT3) suggested BET-dependent activation was partly associated with the STAT3-dependent pathway to maintain the epiblast lineage. To identify BET proteins involved in the formation of the epiblast lineage, we analyzed mutant embryos deficient inBrd4,Brd2, and double mutants. Abolishment of NANOG-positive epiblast cells was only evident inBrd4/Brd2double-deficient morulae. Thus, the phenotype of JQ1-treated embryos is reproduced not by aBrd4- orBrd2-single deficiency, but onlyBrd4/Brd2-double deficiency, demonstrating the redundant roles of BRD2 and BRD4 in the specification of the epiblast lineage.ConclusionsBET proteins are essential to the specification and maintenance of the epiblast lineage by activating lineage-specific core transcription factors during mouse preimplantation development. Among BET proteins, BRD4 plays a central role and BRD2 a complementary role in the specification and maintenance of epiblast lineages. Additionally, BET-dependent maintenance of the epiblast lineage may be partly associated with the STAT3-dependent pathway.
Hematopoietic differentiation is characterized by a transient peak of entropy at a single-cell level
Authors: Dussiau Charles , Boussaroque Agathe , Gaillard Mathilde , Bravetti Clotilde , Zaroili Laila , Knosp Camille , Friedrich Chloé , Asquier Philippe , Willems Lise , Quint Laurent , Bouscary Didier , Fontenay Michaela , Espinasse Thibault , Plesa Adriana , Sujobert Pierre , Gandrillon Olivier , Kosmider Olivier 
Published: March 2022

Abstract
Background
Mature blood cells arise from hematopoietic stem cells in the bone marrow by a process of differentiation along one of several different lineage trajectories. This is often represented as a series of discrete steps of increasing progenitor cell commitment to a given lineage, but as for differentiation in general, whether the process is instructive or stochastic remains controversial. Here, we examine this question by analyzing single-cell transcriptomic data from human bone marrow cells, assessing cell-to-cell variability along the trajectories of hematopoietic differentiation into four different types of mature blood cells. The instructive model predicts that cells will be following the same sequence of instructions and that there will be minimal variability of gene expression between them throughout the process, while the stochastic model predicts a role for cell-to-cell variability when lineage commitments are being made.

Results
Applying Shannon entropy to measure cell-to-cell variability among human hematopoietic bone marrow cells at the same stage of differentiation, we observed a transient peak of gene expression variability occurring at characteristic points in all hematopoietic differentiation pathways. Strikingly, the genes whose cell-to-cell variation of expression fluctuated the most over the course of a given differentiation trajectory are pathway-specific genes, whereas genes which showed the greatest variation of mean expression are common to all pathways. Finally, we showed that the level of cell-to-cell variation is increased in the most immature compartment of hematopoiesis in myelodysplastic syndromes.

Conclusions
These data suggest that human hematopoietic differentiation could be better conceptualized as a dynamical stochastic process with a transient stage of cellular indetermination, and strongly support the stochastic view of differentiation. They also highlight the need to consider the role of stochastic gene expression in complex physiological processes and pathologies such as cancers, paving the way for possible noise-based therapies through epigenetic regulation.
Fluid shear stress enhances T cell activation through Piezo1
Authors: Hope Jacob M. , Dombroski Jenna A. , Pereles Rebecca S. , Lopez-Cavestany Maria , Greenlee Joshua D. , Schwager Samantha C. , Reinhart-King Cynthia A. , King Michael R. 
Published: March 2022

Abstract
Background
T cell activation is a mechanical process as much as it is a biochemical process. In this study, we used a cone-and-plate viscometer system to treat Jurkat and primary human T cells with fluid shear stress (FSS) to enhance the activation of the T cells through mechanical means.

Results
The FSS treatment of T cells in combination with soluble and bead-bound CD3/CD28 antibodies increased the activation of signaling proteins essential for T cell activation, such as zeta-chain-associated protein kinase-70 (ZAP70), nuclear factor of activated T cells (NFAT), nuclear factor kappa B (NF-κB), and AP-1 (activator protein 1). The FSS treatment also enhanced the expression of the cytokines tumor necrosis factor alpha (TNF-α), interleukin 2 (IL-2), and interferon gamma (IFN-γ), which are necessary for sustained T cell activation and function. The enhanced activation of T cells by FSS was calcium dependent. The calcium signaling was controlled by the mechanosensitive ion channel Piezo1, as GsMTx-4 and Piezo1 knockout reduced ZAP70 phosphorylation by FSS.

Conclusions
These results demonstrate an intriguing new dynamic to T cell activation, as the circulatory system consists of different magnitudes of FSS and could have a proinflammatory role in T cell function. The results also identify a potential pathophysiological relationship between T cell activation and FSS, as hypertension is a disease characterized by abnormal blood flow and is correlated with multiple autoimmune diseases.