bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromatin accessibility and transcriptome integrative analysis revealed AP-1-mediated genes potentially modulate histopathology features in psoriasis
Authors: Xu Xiaoqing , Tang Xianfa , Zhang Yuxi , Pan Zhaobing , Wang Qingping , Tang Lili , Zhu Caihong , Cheng Hui , Zhou Fusheng 
Published: March 2022

Abstract
Background
Psoriasis is a chronic and hyperproliferative skin disease featured by hyperkeratosis with parakeratosis, Munro micro-abscess, elongation of rete pegs, granulosa thinning, and lymphocyte infiltration. We previously profiled gene expression and chromatin accessibility of psoriatic skins by transcriptome sequencing and ATAC-seq. However, integrating both of these datasets to unravel gene expression regulation is lacking. Here, we integrated transcriptome and ATAC-seq of the same psoriatic and normal skin tissues, trying to leverage the potential role of chromatin accessibility and their function in histopathology features.

Results
By inducing binding and expression target analysis (BETA) algorithms, we explored the target prediction of transcription factors binding in 15 psoriatic and 19 control skins. BETA identified 408 upregulated genes (rank product < 0.01) and 133 downregulated genes linked with chromatin accessibility. We noticed that cumulative fraction of genes in upregulation group was statistically higher than background, while that of genes in downregulation group was not significant. KEGG pathway analysis showed that the upregulated 408 genes were enriched in TNF, NOD, and IL-17 signaling pathways. In addition, the motif module in BETA suggested the 57 upregulated genes are targeted by transcription factor AP-1, indicating that increased chromatin accessibility facilitated the binding of AP-1 to the target regions and further induced expression of relevant genes. Among these genes, SQLE, STRN, EIF4, and MYO1B expression was increased in patients with hyperkeratosis, parakeratosis, and acanthosis thickening.

Conclusions
In summary, with the advantage of BETA, we identified a series of genes that contribute to the disease pathogenesis, especially in modulating histopathology features, providing us with new clues in treating psoriasis.
The microbiota restrains neurodegenerative microglia in a model of amyotrophic lateral sclerosis
Authors: Cox Laura M. , Calcagno Narghes , Gauthier Christian , Madore Charlotte , Butovsky Oleg , Weiner Howard L. 
Published: March 2022

Abstract
Background
The gut microbiota can affect neurologic disease by shaping microglia, the primary immune cell in the central nervous system (CNS). While antibiotics improve models of Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and the C9orf72 model of amyotrophic lateral sclerosis (ALS), antibiotics worsen disease progression the in SOD1G93A model of ALS. In ALS, microglia transition from a homeostatic to a neurodegenerative (MGnD) phenotype and contribute to disease pathogenesis, but whether this switch can be affected by the microbiota has not been investigated.

Results
In this short report, we found that a low-dose antibiotic treatment worsened motor function and decreased survival in the SOD1 mice, which is consistent with studies using high-dose antibiotics. We also found that co-housing SOD1 mice with wildtype mice had no effect on disease progression. We investigated changes in the microbiome and found that antibiotics reduced Akkermansia and butyrate-producing bacteria, which may be beneficial in ALS, and cohousing had little effect on the microbiome. To investigate changes in CNS resident immune cells, we sorted spinal cord microglia and found that antibiotics downregulated homeostatic genes and increased neurodegenerative disease genes in SOD1 mice. Furthermore, antibiotic-induced changes in microglia preceded changes in motor function, suggesting that this may be contributing to disease progression.

Conclusions
Our findings suggest that the microbiota play a protective role in the SOD1 model of ALS by restraining MGnD microglia, which is opposite to other neurologic disease models, and sheds new light on the importance of disease-specific interactions between microbiota and microglia.
In-vitro assessment of the efficiency of cold atmospheric plasma on decontamination of titanium dental implants
Authors: Flörke Christian , Janning Josephine , Hinrichs Cedric , Behrens Eleonore , Liedtke Kim Rouven , Sen Sinan , Christofzik David , Wiltfang Jörg , Gülses Aydin 
Published: March 2022

Abstract
Background
The aim of the current study was to comparatively assess the efficiency of three different adjunctive therapy options (cold atmospheric plasma, [CAP], photodynamic therapy [PDT] and chemical decontamination via 35% phosphoric acid gel [PAG]) on decontamination of titanium implant surfaces in-vitro.

Materials and methods
Implants were inserted in concavities of four mm in depth mimicking a bone defect at the implant recipient site. In each model, two implants were inserted in the fourth and one implant in the third quadrants. After contamination with E. faecalis, the first group has been treated with CAP for 3 min, the second group with 35% PAG (and the third group with PDT. After treatment, quantification of bacterial colonization was assessed by quantification via colony forming units and qualitatively by fluorescence microscopy and scanning electron microscopy.

Results
With a mean value of 1.24 × 105 CFU/ml, the CAP treated implants have showed the least microorganisms. The highest number of CFU was found after PDT with mean value of 8.28 × 106 CFU/ml. For the implants that were processed with phosphoric acid, a mean value of 3.14 × 106 CFU/ml could be detected. When the groups were compared, only the CAP and PDT groups differed significantly from each other (p = 0.005).

Conclusion
A complete cleaning of the micro-textured implant surface or the killing of the bacteria could not be achieved by any of the investigated treatment options, thus bacteria in the microstructure of the titanium surface cannot be completely reached by mechanical and physico-chemical processes.

Clinical relevance
The main goal of the adjunctive peri-implantitis treatment is the decontamination of the implant surface. However, there is still an ongoing need to define the most appropriate adjunctive therapy method. Due to its antimicrobial effects, CAP combined with mechanical debridement could be a feasible treatment modality in the management of peri-implantitis.
Study of the Awareness of Adoption as a Family-Building Option Among Oncofertility Stakeholders in Japan
Authors: Shiraishi Eriko , Sugimoto Kouhei , Shapiro Jason Solomon , Ito Yuki , Kamoshita Keiko , Kusuhara Atsuko , Haino Takayuki , Koizumi Tomoe , Okamoto Aikou , Suzuki Nao 
Published: March 2022

Purpose The oncofertility decision tree was developed by the oncofertility consortium as a tool to support healthcare professionals and patients through the complicated process of deciding the most appropriate fertility preservation strategy for patients with cancer. Various strategies include oocyte retrieval, oocyte donation, use of a gestational carrier and adoption. However, differences in the cultural and legal landscape present serious barriers to utilizing some of these strategies in Japan. Patients and Methods We surveyed Japanese oncofertility stakeholders including 60 cancer survivors, 27 oncology facilities, 78 reproductive medicine facilities and 15 adoption agencies by a questionnaire to characterize awareness among oncofertility stakeholders in Japan about parenting options including adoption to inform work to establish guidelines for decision-making by cancer survivors in an oncofertility. Results Our results indicate that oncologists and reproductive endocrinologists in Japan have an insufficient understanding of adoption that prevents them from adequately informing their patients. Japanese cancer survivors self-describe a lack in confidence in finding a suitable partner and raising a child. Contrastingly, of the 9 adoption agencies which responded, no agency included being a cancer survivor as a criterion for disqualification and 4 of 9 (44%) adoption agencies reported at least 1 adoption to a cancer survivor in the last year. Conclusion Our work demonstrates that a cancer survivor’s medical history itself is not a hurdle to adoption and investment in patient-provider education could be a viable strategy to improve the utilization of adoption as a fertility preservation strategy in Japan.
Effect of AZD4017, a Selective 11β-HSD1 Inhibitor, on Bone Turnover Markers in Postmenopausal Osteopenia
Authors: Abbas Afroze , Schini Marian , Ainsworth Gemma , Brown Sarah R , Oughton Jamie , Crowley Rachel K , Cooper Mark S , Fairclough Rebecca J , Eastell Richard , Stewart Paul M 
Published: March 2022

Abstract

Context
The causative link between circulating glucocorticoid excess and osteoporosis is well-established. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which increases local cortisol production, is expressed in human osteoblasts and its activity increases with age.

Objective
We hypothesized that local 11β-HSD1 might mediate an age-related decrease in bone formation and that selective 11β-HSD1 inhibition may enhance bone formation.

Methods
A dual-center, phase II, randomized, double-blind, placebo-controlled trial of 90 days’ treatment with AZD4017 (a selective 11β-HSD1 inhibitor) was conducted in 55 postmenopausal women with osteopenia. Participants received 400 mg oral AZD4017 twice daily vs matched placebo over 90 days. The primary outcome measure was the impact on the bone formation marker osteocalcin. Secondary objectives included correlation with 11β-HSD1 activity.

Results
At 90 days, osteocalcin levels did not differ between treatment groups: active (mean 22.3 [SD 8.6] ng/mL, n = 22) and placebo (21.7 [SD 9.2] ng/mL, n = 24), with a baseline-adjusted treatment effect of 0.95 (95% CI: −2.69, 4.60). The results from the urinary [THF + alloTHF]/THE ratio (index of 11β-HSD1 activity) and the urinary cortisol/cortisone ratio (index of 11β-HSD2 activity) confirmed a &gt; 90% inhibition of 11β-HSD1 but no change in activity of 11β-HSD2.

Conclusion
This trial demonstrates that AZD4017 selectively inhibits 11β-HSD1 activity in vivo in a safe and reversible manner. Following 90 days of treatment, there is no effect on bone formation, indicating that the relative impairment of bone mineral density in postmenopausal women is not mediated by local intracellular production of cortisol under normal physiological concentrations.
Low Plasma Ionized Calcium Is Associated With Increased Mortality: A Population-based Study of 106 768 Individuals
Authors: Kobylecki Camilla J , Nordestgaard Børge G , Afzal Shoaib 
Published: March 2022

AbstractContextLow circulating total calcium or albumin-adjusted calcium has been associated with higher mortality, especially in hospital settings; however, these measures tend to misclassify patients with derangements in calcium homeostasis.ObjectiveAs the association of the biologically active ionized calcium with mortality is poorly elucidated, we tested the hypothesis that low plasma ionized calcium is associated with higher risk of all-cause and cause-specific mortality in the general population.MethodsWe included 106 768 individuals from the Copenhagen General Population Study. Information on all-cause and cause-specific mortality was from registries and risks were calculated using Cox regression and competing-risks regression by the STATA command stcompet.ResultsDuring a median follow-up period of 9.2 years, 11 269 individuals died. Each 0.1 mmol/L lower plasma ionized calcium below the median of 1.21 mmol/L was associated with a multivariable adjusted hazard ratio of 1.23 (95% CI, 1.10-1.38) for all-cause mortality. Corresponding hazard ratios for cancer and other mortality were 1.29 (1.06-1.57) and 1.24 (1.01-1.53), respectively. In contrast, for cardiovascular mortality, only high plasma ionized calcium was associated with mortality with a hazard ratio of 1.17 (1.02-1.35) per 0.1 mmol/L higher plasma ionized calcium above the median. We found no interactions between plasma ionized calcium and preexisting cardiovascular or renal disease on all-cause mortality.ConclusionIn the general population, low plasma ionized calcium was associated with increased all-cause, cancer, and other mortality, while high levels were associated with increased cardiovascular mortality.
Endotoxin Biomarkers Are Associated With Adiposity and Cardiometabolic Risk Across 6 Years of Follow-up in Youth
Authors: Perng Wei , Friedman Jacob E , Janssen Rachel C , Glueck Deborah H , Dabelea Dana 
Published: March 2022

Abstract

Context
Metabolic endotoxemia may be a shared mechanism underlying childhood obesity and early-onset metabolic diseases (eg, type 2 diabetes, nonalcoholic fatty liver disease).

Objective
Examine prospective associations of serum endotoxin biomarkers lipopolysaccharide (LPS) and its binding protein, LPS binding protein (LBP), and anti-endotoxin core immunoglobulin G (EndoCab IgG) with adiposity and cardiometabolic risk in youth.

Design/setting
This prospective study included 393 youth in the Exploring Perinatal Outcomes Among Children cohort in Colorado. Participants were recruited from 2006 to 2009 at age 10 years (baseline) and followed for 6 years (follow-up). We examined associations of endotoxin biomarkers at baseline with adiposity [body mass index (BMI) z-score, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), skinfolds, waist circumference] and cardiometabolic risk (insulin, glucose, adipokines, lipid profile, blood pressure) across both visits using mixed-effects regression, and with hepatic fat fraction (HFF) at follow-up using linear regression.

Results
Higher LPS and LBP predicted greater adiposity across follow-up. Each 1-unit log-transformed LPS corresponded with 0.23 (95% CI 0.03, 0.43) units BMI z-score, 5.66 (95% CI 1.99, 9.33) mm3 VAT, 30.7 (95% CI 8.0, 53.3) mm3 SAT, and 8.26 (95% CI 4.13, 12.40) mm skinfold sum. EndoCab IgG was associated with VAT only [3.03 (95% CI 0.34, 5.71) mm3]. LPS was associated with higher insulin [1.93 (95% CI 0.08, 3.70) µU/mL] and leptin [2.28 (95% CI 0.66, 3.90) ng/mL] and an adverse lipid profile. No association was observed with HFF. Accounting for pubertal status and lifestyle behaviors did not change findings. However, adjustment for prepregnancy BMI and gestational diabetes attenuated most associations.

Conclusions
Serum endotoxin may be a marker of pathophysiological processes underlying development of childhood obesity and cardiometabolic conditions associated with exposure to fetal overnutrition.
“Why Don’t You Go to Nursing School?”
Authors: Kozma Liat , Nuriely Benny 
Published: March 2022

Abstract
The article analyzes the gendered experience at Hebrew University Medical School in its first two decades, 1950–70. Contrary to earlier studies on women in medicine, which focused on immigrant doctors to late Ottoman and mandatory Palestine, gendering the future cadre of doctors in post-1948 Israel has not been discussed. Based on archival documents, newspapers of the period, and interviews with the school’s graduates, the article argues that the school maintained a consistent though informal quota policy, which also differentiated between country-born and immigrant students. It examines students’ interactions with the school, beginning with their decision to apply for medical school and going through the interview process, the experience of student life, and their attempts to balance medical school with marriage and motherhood.
The Affective Politics of Care in Trans Crowdfunding
Authors: Barcelos Chris 
Published: March 2022

AbstractTrans-for-trans crowdfunding is a common strategy to raise money both for gender-affirming medical care and for survival expenses related to living in a transphobic world. Although crowdfunding is infrequently successful in funding our survival needs, there have been few attempts to theorize what this form of mutual aid accomplishes. The objective of this article is to explore the possibilities and limits of trans crowdfunding as part of a critical trans political project. Drawing on the emergent body of scholarship in trans care and the cultural sites in which t4t crowdfunding circulates, this article asks: how does thinking about trans crowdfunding as an affect, labor, and politics of care help us understand its utility, even in the face of its failures to redistribute wealth and meet our material needs? The author argues that trans crowdfunding functions as a form of “complicit care” that simultaneously furthers both our marginalization and our collective liberation.
“Necessary Bonding”
Authors: Lundy-Harris Amira 
Published: March 2022

Abstract
This article uses a t4t framework rooted in Black feminist thought to meditate on the convergence of Black and trans in meetings between fields, encounters with text, and relational bonds forged between individuals that help promote collective creation. Section 1 explores the bridging of Black feminist thought and trans studies in relationship to the emergence of Black trans studies. The second section examines how the searching Black trans reader's encounter with the text allows for the imagination and creation of an actualized trans self. Section 3 takes a more conventional approach to the concept of t4t, exploring the kin bonds created between Black trans people, with an eye to the way that Black feminist literature is used to describe these relationships.
Piezo1 activation attenuates thrombin-induced blebbing in breast cancer cells
Authors: O'Callaghan Paul , Engberg Adam , Eriksson Olle , Fatsis-Kavalopoulos Nikos , Stelzl Christina , Sanchez Gonzalo , Idevall-Hagren Olof , Kreuger Johan 
Published: March 2022

ABSTRACT
Cancer cells exploit a variety of migration modes to leave primary tumors and establish metastases, including amoeboid cell migration, which is typically reliant on bleb formation. Here we demonstrate that thrombin induces dynamic blebbing in the MDA-MB-231 breast cancer cell line and confirm that protease-activated receptor 1 (PAR1) activation is sufficient to induce this effect. Cell confinement has been implicated as a driving force in bleb-based migration. Unexpectedly, we found that gentle contact compression, exerted using a custom built ‘cell press’ to mechanically stimulate cells, reduced thrombin-induced blebbing. Thrombin-induced blebbing was similarly attenuated using the small molecule Yoda1, an agonist of the mechanosensitive Ca2+ channel Piezo1, and this attenuation was impaired in Piezo1-depleted cells. Additionally, Piezo1 activation suppressed thrombin-induced phosphorylation of ezrin, radixin and moesin (ERM) proteins, which are implicated in the blebbing process. Our results provide mechanistic insights into Piezo1 activation as a suppressor of dynamic blebbing, specifically that which is induced by thrombin.
Prevalence of depressive symptoms in patients with chronic physical illness: A single institutional cross-sectional study from Nepal
Authors: Mahara Rawal Namrata , Adhikari Suman Prasad , Rajbhandari Sabin , Bhusal Santosh , Gupta Sonali , Piya Shreya Bhasu , K.C Soniya , Lama Susan , Shrestha Dhan Bahadur 
Published: March 2022

Background Depression is a global public health problem. Studies show comorbid depression increases morbidity, mortality, and associated risk of poor adherence compared to those without depression. Materials and Method An analytical cross-sectional study was conducted among 326 patients who met the inclusion criteria. They were selected following simple random sampling from medical OPD and ward of Shree Birendra Hospital Kathmandu, Nepal. Semi-structured interview schedule (SSIS), Beck Depression Inventory-II (BDI-II), and Kuppuswamy’s Scale (KS) were used for data collection. Data analysis was done using SPSS version 26 and STATA version 15. Simple frequency distribution of attributes presented in tables and association assessed using Chi-square/ Fisher’s exact test. Further, the relation between depression and other independent factors is quantified using multivariate/ multivariable logistics regression analyses. Result Using Beck depression inventory (BDI-II) as a tool to determine depression 52.1% (n=170) had minimal or no depression, 16.9% (n=55) had mild depression, 18.7 %( n=61) had moderate depression and 12.3% (n=40) had severe depression i.e. 47.9% of population had some form of depression. Prevalence of depression among patient with single comorbidity found to be 30.9% (n=25, N=81) for hypertension, 43.3% (n=13, N=30) for diabetes mellitus, 45.6% (n=31, N=68) for chronic obstructive pulmonary disease, 77.5% (n=31, N=40) for chronic kidney disease, and 60 %( n=9, N=15) for chronic heart disease. Depression among patient with multiple comorbidities (more than one disease above mention) was found to be 51.1% (n=47, N=92). Prevalence of depression was more among patients with history of longer duration of illness; 11 years and above 52.9 % (n=36, N=68); 6-10 years 48.3 % (n=43, N=89); 1-5 years 45.6 %( n=77, N=169). Conclusion This study showed that the prevalence of depression has a significant relationship with the duration of illness. Therefore, early recognition and treatment play a crucial role in reducing the effects of depression.
Effectiveness of acute L-arginine supplementation on physical performance in strength training: a systematic review and meta-analysis
Authors: Pasa Camila , Godinho de Oliveira Ruberlei , da Rosa Lima Thiago , Jalousie Kommers Michelle , Régia Ferreira Viana Figueiredo Karla , Christiane Rezende Fett Waléria , Alexandre Fett Carlos 
Published: March 2022

Background: The oral administration of L-arginine has been related to improved physical performance due to a likely reduction in muscle fatigue, resulting from the vasodilator effect of nitric oxide on skeletal muscle. However, there is no precise and quantitative analysis of the information in the literature. The main objective of this study was to assess the effectiveness of L-arginine supplementation on physical performance in strength training with a systematic review and meta-analysis. We hypothesized that L-arginine supplementation would improve performance capacity and the effects involved in strength training. Methods: The study period was from 2010 to 2020. The inclusion process established articles with well-designed human experiments that included only L-arginine supplementation (without any additional compounds) testing the effects of L-arginine supplementation on sports performance related to strength training; identical experimental conditions in placebo or control group; and publications in the last ten years (until December 31, 2020). Three studies were included that compared L-arginine supplementation with placebo in anaerobic performance tests. Test analysis supplementation with other supplements was removed and there was no gender, age, and ethnicity level. Results: There was no significant heterogeneity (p>0.05) in the analysis of the three selected articles and the effects of L-arginine supplementation in muscular endurance; performance had a mean of 0.26 (95% CI = -0.129; 0.649; p = 0.190), peak torque with a mean of -0.002 (95% CI = -0.531; 0.527; p = 0. 99) of the third series of exercises and, furthermore, when comparing the integrated effect (resistance rate with the peak torque) there was no difference with a mean of 0.168 (95% CI = -0.145; 0.481; p = 0.292). Conclusions: Acute L-arginine supplementation provides no ergogenic effect on strength training performance.