bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating SARS-CoV-2+ megakaryocytes are associated with severe viral infection in COVID-19
Authors: Fortmann Seth D. , Patton Michael J. , Frey Blake F. , Tipper Jennifer L. , Reddy Sivani B. , Vieira Cristiano P. , Hanumanthu Vidya Sagar , Sterrett Sarah , Floyd Jason L. , Prasad Ram , Zucker Jeremy D. , Crouse Andrew B. , Huls Forest , Chkheidze Rati , Li Peng , Erdmann Nathaniel B. , Harrod Kevin S. , Gaggar Amit , Goepfert Paul A. , Grant Maria B. , Might Matthew 
Published: March 2023

Abstract
Several independent lines of evidence suggest that megakaryocytes are dysfunctional in severe COVID-19. Herein, we characterized peripheral circulating megakaryocytes in a large cohort of inpatients with COVID-19 and correlated the subpopulation frequencies with clinical outcomes. Using peripheral blood, we show that megakaryocytes are increased in the systemic circulation in COVID-19, and we identify and validate S100A8/A9 as a defining marker of megakaryocyte dysfunction. We further reveal a subpopulation of S100A8/A9+ megakaryocytes that contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein and RNA. Using flow cytometry of peripheral blood and in vitro studies on SARS-CoV-2–infected primary human megakaryocytes, we demonstrate that megakaryocytes can transfer viral antigens to emerging platelets. Mechanistically, we show that SARS-CoV-2–containing megakaryocytes are nuclear factor κB (NF-κB)-activated, via p65 and p52; express the NF-κB–mediated cytokines interleukin-6 (IL-6) and IL-1β; and display high surface expression of Toll-like receptor 2 (TLR2) and TLR4, canonical drivers of NF-κB. In a cohort of 218 inpatients with COVID-19, we correlate frequencies of megakaryocyte subpopulations with clinical outcomes and show that SARS-CoV-2–containing megakaryocytes are a strong risk factor for mortality and multiorgan injury, including respiratory failure, mechanical ventilation, acute kidney injury, thrombotic events, and intensive care unit admission. Furthermore, we show that SARS-CoV-2+ megakaryocytes are present in lung and brain autopsy tissues from deceased donors who had COVID-19. To our knowledge, this study offers the first evidence implicating SARS-CoV-2+ peripheral megakaryocytes in severe disease and suggests that circulating megakaryocytes warrant investigation in inflammatory disorders beyond COVID-19.
Melanocortin/MC5R axis regulates the proliferation of hematopoietic stem cells in mice after ionizing radiation injury
Authors: Chen Naicheng , Quan Yong , Chen Mo , Lu Yukai , Yang Lijing , Wang Song , Chen Fang , Xu Yang , Shen Mingqiang , Zeng Hao , Chen Shilei , Wang Fengchao , Wang Junping , Hu Mengjia 
Published: March 2023

Abstract
Hematopoietic stem cells (HSCs) possess great self-renewal and multidirectional differentiation abilities, which contribute to the continuous generation of various blood cells. Although many intrinsic and extrinsic factors have been found to maintain HSC homeostasis, the precise regulation of hematopoiesis under stress conditions is poorly understood. In this study, we show that melanocortin receptor 5 (MC5R) is abundantly expressed in hematopoietic stem progenitor cells (HSPCs). Using an MC5R knockout mouse model, we observed that it is not essential for steady-state hematopoiesis. Interestingly, the levels of α-melanocyte stimulating hormone (α-MSH), an important subtype of melanocortin, were elevated in the serum and bone marrow, and the expression of MC5R was upregulated in HSPCs from mice after irradiation. MC5R deficiency aggravates irradiation-induced myelosuppression because of impaired proliferation and reconstitution of HSCs. Further investigation revealed that the melanocortin/MC5R axis regulates the proliferation of HSCs by activating the PI3K/AKT and MAPK pathways. More importantly, α-MSH treatment can significantly accelerate hematopoietic recovery in irradiated mice. In conclusion, our data demonstrate that the melanocortin/MC5R axis plays a crucial role in regulating HSC proliferation under stress, thus providing a promising strategy to promote hematopoietic regeneration when suffering from injury.
MicroRNA-Transcription factor regulatory networks in the early strobilar development of Echinococcus granulosus protoscoleces
Authors: Mohammadi Mohammad Ali , Mansouri Mehdi , Derakhshani Ali , Rezaie Masoud , Borhani Mehdi , Nasibi Saeid , Mousavi Seyed Mohammad , Afgar Ali , Macchiaroli Natalia , Rosenzvit Mara C. , Harandi Majid Fasihi 
Published: March 2023

Abstract
Background
Echinococcus granulosus sensu lato has a complex developmental biology with a variety of factors relating to both intermediate and final hosts. To achieve maximum parasite adaptability, the development of the cestode is dependent on essential changes in transcript regulation. Transcription factors (TFs) and miRNAs are known as master regulators that affect the expression of downstream genes through a wide range of metabolic and signaling pathways. In this study, we aimed to develop a regulatory miRNA-Transcription factor (miRNA-TF) network across early developmental stages of E. granulosus protoscoleces by performing in silico analysis, and to experimentally validate TFs expression in protoscoleces obtained from in vitro culture, and from in vivo experiments.

Results
We obtained list of 394 unique E. granulosus TFs and matched them with 818 differentially expressed genes which identified 41 predicted TFs with differential expression. These TFs were used to predict the potential targets of 31 differentially expressed miRNAs. As a result, eight miRNAs and eight TFs were found, and the predicted network was constructed using Cytoscape. At least four miRNAs (egr-miR-124a, egr-miR-124b-3p, egr-miR-745-3p, and egr-miR-87-3p) and their corresponding differentially expressed TFs (Zinc finger protein 45, Early growth response protein 3, Ecdysone induced protein 78c and ETS transcription factor elf 2) were highlighted in this investigation. The expression of predicted differentially expressed TFs obtained from in vitro and in vivo experiments, were experimentally validated by quantitative polymerase chain reaction. This confirmed findings of RNA-seq data.

Conclusion
miRNA-TF networks presented in this study control some of the most important metabolic and signaling pathways in the development and life cycle of E. granulosus, providing a potential approach for disrupting the early hours of dog infection and preventing the development of the helminth in the final host.
Nutrient availability of roughages in isocaloric and isonitrogenous diets alters the bacterial networks in the whole gastrointestinal tract of Hu sheep
Authors: Li Yuqi , Gao Jian , Xue Yihan , Sun Ruolin , Sun Xiaoni , Sun Zhanying , Liu Suozhu , Tan Zhankun , Zhu Weiyun , Cheng Yanfen 
Published: March 2023

Abstract
Background
The nutrient availability of roughages could affect the dietary utilization efficiency of ruminants even in isocaloric and isonitrogenous diets. Here, we analyzed the bacterial composition and their metabolic pathways in the gastrointestinal tracts (GITs) of Hu sheep fed with wheat straw (WS) instead of alfalfa (AL) in isocaloric and isonitrogenous diets, trying to explore the reasons from the perspective of GITs bacterial network structure changes.

Results
We employed 16S rRNA gene sequencing in combination with the Kruskal–Wallis test, Spearman correlation analysis, and other statistical methods to describe the microbiota composition in the GITs of Hu sheep. The results showed after the roughage was replaced from AL to WS, the most positive response occurred in the rumen microbiota, resulting in a more obvious microbiological and functional redundancy phenomenon. Whereas extended biogeographic studies of the GITs bacterial community found opposite results for the hindgut microbiota and metabolism networks compared to the forestomach. The abundance of fiber-degrading bacteria such as Prevotella, Oscillospiraceae NK4A214 group, and Treponema was significantly increased in GITs, but low-efficiency crude fiber degradation inhibited energy use efficiency, the pentose phosphate pathway, gluconeogenesis, and volatile acid synthesis. In addition, dietary shifting from AL to WS decreased the abundance of beneficial bacteria such as the Lachnospiraceae NK3A20 group and Alistipes, thereby enhancing the underlying inflammatory response.

Conclusions
These findings suggest that feeding untreated WS affected the structure and function of the bacterial network in the GITs due to limited total digestible nutrients, and in particular increases the complexity of the rumen bacterial network, and limit the abundance of bacteria involved in the crude fiber degradation in the hindgut.
PRIMIS: design of a pivotal, randomized, phase 3 study evaluating the safety and efficacy of the nonsteroidal farnesoid X receptor agonist cilofexor in noncirrhotic patients with primary sclerosing cholangitis
Authors: Trauner Michael , Chung Chuhan , Sterling Kate , Liu Xiangyu , Lu Xiaomin , Xu Jun , Tempany-Afdhal Clare , Goodman Zachary D. , Färkkilä Martti , Tanaka Atsushi , Trivedi Palak , Kowdley Kris V. , Bowlus Christopher L. , Levy Cynthia , Myers Robert P. 
Published: March 2023

Abstract
Background
Primary sclerosing cholangitis (PSC) is a chronic progressive liver disease leading to biliary fibrosis and cirrhosis. Cilofexor is a nonsteroidal farnesoid X receptor agonist that demonstrated significant improvements in liver biochemistry and markers of cholestasis in patients with PSC in a phase 2 study. We describe here the rationale, design, and implementation of the phase 3 PRIMIS trial, the largest placebo-controlled trial in PSC.

Methods
Adults with large-duct PSC without cirrhosis are randomized 2:1 to receive oral cilofexor 100 mg once daily or placebo for up to 96 weeks during the blinded phase. Patients completing the blinded phase are eligible to receive open-label cilofexor 100 mg daily for up to 96 weeks. The primary objective is to evaluate whether cilofexor reduces the risk of fibrosis progression compared with placebo. Liver biopsy is performed at screening and Week 96 of the blinded phase for histologic assessment of fibrosis. The primary endpoint—chosen in conjunction with guidance from the U.S. Food and Drug Administration—is the proportion of patients with ≥ 1-stage increase in fibrosis according to Ludwig histologic classification at week 96. Secondary objectives include evaluation of changes in liver biochemistry, serum bile acids, liver fibrosis assessed by noninvasive methods, health-related quality of life, and safety of cilofexor.

Conclusion
The phase 3 PRIMIS study is the largest randomized, double-blind, placebo-controlled trial in PSC to date and will allow for robust evaluation of the efficacy and safety of cilofexor in noncirrhotic patients with large-duct PSC.
Trial Registration: ClinicalTrials.gov NCT03890120; registered 26/03/2019.
The differences in drug resistance between drug-resistant tuberculosis patients with and without diabetes mellitus in northeast China: a retrospective study
Authors: Pan Yuanping , Yu Yingying , Yi Yaohui , Dou Xiaofeng , Lu Jiachen , Zhou Ling 
Published: March 2023

Abstract
Background
Diabetes mellitus (DM) and drug-resistant tuberculosis (DR-TB) are serious global public health problems. This study aimed to explore the differences in drug resistance between DR-TB patients with and without DM. Risk factors for developing multidrug-resistant tuberculosis (MDR-TB) were also investigated among DR-TB patients.

Methods
The patient’s basic demographic,　clinical characteristics, and drug susceptibility testing (DST) data were collected from the Chinese Disease Control Information System. Descriptive statistics were used to estimate the frequency and proportion of included variables. Categorical variables were compared using the Chi-square test or Fisher’s exact test. Chi-square tests for trends were used to determine changes and trends in MDR-TB and pre-extensively drug-resistantTB (pre-XDR-TB) patterns over time. Univariate and multivariate logistic regression analysis was used to explore the risk factors of MDR-TB.

Results
Compared with DR-TB patients with DM, DR-TB patients without DM had significantly higher rates of mono-resistant streptomycin (SM) and any resistance to kanamycin (KM), but significantly lower rates of any resistance to protionamide (PTO) and mono-resistance to levofloxacin (LFX), and pre-XDR-TB (P<0.05). The proportion of resistance to other anti-TB drugs was not statistically different between the DR-TB with and without DM. Among DR-TB patients without and with DM, the proportion of patients with MDR-TB and pre-XDR-TB patterns showed a significant downward trend from 2016 to 2021 (P<0.05). Among DR-TB patients without DM, male, previously treated DR-TB cases, and immigration were risk factors for MDR-TB (P<0.05). In DR-TB patients with DM, a negative sputum smear is a risk factor for MDR-TB (P<0.05).

Conclusion
There was no statistical difference in resistance patterns between DR-TB with and without DM, except in arbitrary resistance to PTO and KM, mono-resistant SM and LFX, and pre-XDR-TB. Great progress has been made in the prevention and control of MDR-TB and pre-XDR-TB. However, DR-TB patients with and without DM differ in their risk factors for developing MDR-TB.
Role of self-management program based on 5A nursing model in quality of life among patients undergoing hemodialysis: a Randomized Clinical Trial
Authors: Keivan Sahar , Shariati Abdolali , Miladinia Mojtaba , Haghighizadeh Mohammad Hosein 
Published: March 2023

Abstract
Introduction
Various nursing models are usually employed to achieve self-management and improve the quality of life in chronic conditions. Given its person-based characteristics, the 5 A nursing model can improve the quality of life of hemodialysis patients.

Purpose
This study aimed to determine the role of a self-management program based on the 5 A nursing model in the quality of life of patients undergoing hemodialysis.

Materials and methods
This clinical trial was conducted on hemodialysis patients in Iran. Random sampling was adopted to assign 60 patients to intervention and control groups. After the participants completed a demographic questionnaire and the Kidney Disease Quality of Life–Short Form (KDQOL–SF), routine measures were taken in the control group. However, the 5 A nursing model was implemented in the intervention group for three months. The self-care program was executed in face-to-face sessions or via phone calls and SMSs. After three months, the quality of life was measured again in both groups.

Findings
There were significant differences after the intervention between the intervention and control groups in specific dimensions of quality of life, such as cognitive functions, symptoms, sleep, dialysis, social support, and renal complications (P < 0.05). The two groups also had significant differences in the general scores of quality of life (P < 0.05).

Conclusion
The 5 A self-management intervention as a person-based model could improve self-care in hemodialysis patients. Nurses can implement this model to mitigate care costs, enhance interventions, and improve patients’ quality of life.

Trial registration
Iranian Registry of Clinical Trials (IRCT20211103052955N1; 19/11/2021).
The level of serum albumin is associated with renal prognosis and renal function decline in patients with chronic kidney disease
Authors: Cheng Tong , Wang Xiaoyu , Han Yong , Hao Jianbing , Hu Haofei , Hao Lirong 
Published: March 2023

Abstract
Objective
The study’s purpose is to explore the link of serum albumin on renal progression in patients with chronic kidney disease (CKD).

Methods
This study was a secondary analysis of a prospective cohort study in which a total of 954 participants were non-selectively and consecutively collected from the research of CKD-ROUTE in Japan between November 2010 and December 2011. We evaluated the association between baseline ALB and renal prognosis (initiation of dialysis or 50% decline in eGFR from baseline) and renal function decline (annual eGFR decline) using the Cox proportional-hazards and linear regression models, respectively. We performed a number of sensitivity analyses to ensure the validity of the results. In addition, we performed subgroup analyses.

Results
The included patients had a mean age of (66.86 ± 13.41) years, and 522 (69.23%) were male. The mean baseline ALB and eGFR were (3.89 ± 0.59) g/dL and (33.43 ± 17.97) ml/min/1.73 m2. The annual decline in eGFR was 2.65 mL/min/1.73 m2/year. 218 (28.9%) individuals experienced renal prognosis during a median follow-up period of 36.0 months. The baseline ALB was inversely linked with renal prognosis (HR = 0.61, 95%CI: 0.45, 0.81) and renal function decline (β = -1.41, 95%CI: -2.11, -0.72) after controlling for covariates. The renal prognosis and ALB had a non-linear connection, with ALB’s inflection point occurring at 4.3 g/dL. Effect sizes (HR) were 0.42 (0.32, 0.56) and 6.11 (0.98, 38.22) on the left and right sides of the inflection point, respectively. There was also a non-linear relationship between ALB and renal function decline, and the inflection point of ALB was 4.1 g/dL. The effect sizes(β) on the left and right sides of the inflection point were -2.79(-3.62, -1.96) and 0.02 (-1.97, 1.84), respectively.

Conclusion
This study shows a negative and non-linear association between ALB and renal function decline as well as renal prognosis in Japanese CKD patients. When ALB is lower than 4.1 g/dL, ALB decline was closely related to poor renal prognosis and renal function decline. From a therapeutic point of view, reducing the decline in ALB makes sense for delaying CKD progression.
Changing attitudes towards HIV testing and treatment among three generations of men in Cameroon: a qualitative analysis using the Fogg Behavior Model
Authors: Katirayi Leila , Tchendjou Patrice , Tchounga Boris , Mbunka Muhamed , Wicks Madison , Conserve Donaldson F. 
Published: March 2023

Abstract
Introduction
Men are less likely than women to test for HIV and promptly initiate antiretroviral treatment, resulting in advanced HIV disease and increased mortality rates among them.

Methods
In-depth interviews were conducted with men and leaders in the west and central regions of Cameroon. Men were recruited from existing community groups and stratified by age: 21–30 years, 31–40 years, and 41 years and older. Community leaders were recommended by the community dialogue structure chairman. Interviews were conducted using a semi-structured guide in English or French, depending on the participant’s preference. Transcripts were coded in the MAXQDA v.12 software and analyzed using thematic analysis and by age group. The Fogg Behavior Model was used to gain a deeper understanding of the different perceptions across all age groups.

Results
Younger men (21–30 years) were generally more accepting of HIV testing, as it had become normative behavior. Although financial barriers could limit access, free testing was mentioned as a prompt to initiate HIV testing. The middle age men (31–40 years) had the most concerns about HIV testing interrupting their work day and recommended increasing testing locations and hours. The older men (41 + years) were the least motivated to get tested, citing worries about the impact on their social standing within the community. All age groups reported being motivated to begin treatment if they were found to be HIV-positive.
Participants also provided insights regarding community HIV testing and treatment messaging. Younger and older men preferred to hear directly from qualified health professionals, but younger men noted that social media, radio, and TV could be utilized. Middle age men also identified TV and radio as effective mediums, if door-to-door messaging was not an option.

Conclusions
The study highlights important considerations when planning future information-sharing activities for HIV testing and treatment. Since lived experiences differ across generations and societal roles continue to change, not only should the content of messages differ among the generations, but the means of communication must also be considered to ensure the messages are conveyed through a trusted source.
A qualitative exploration into the presence of TB stigmatization across three districts in South Africa
Authors: DeSanto Daniel , Velen Kavindhran , Lessells Richard , Makgopa Sewele , Gumede Dumile , Fielding Katherine , Grant Alison D , Charalambous Salome , Chetty-Makkan Candice M 
Published: March 2023

Abstract
Background
Tuberculosis (TB) stigma is a barrier to active case finding and delivery of care in fighting the TB epidemic. As part of a project exploring different models for delivery of TB contact tracing, we conducted a qualitative analysis to explore the presence of TB stigma within communities across South Africa.

Methods
We conducted 43 in-depth interviews with 31 people with TB and 12 household contacts as well as five focus group discussions with 40 ward-based team members and 11 community stakeholders across three South African districts.

Results
TB stigma is driven and facilitated by fear of disease coupled with an understanding of TB/HIV duality and manifests as anticipated and internalized stigma. Individuals are marked with TB stigma verbally through gossip and visually through symptomatic identification or when accessing care in either TB-specific areas in health clinics or though ward-based outreach teams. Individuals’ unique understanding of stigma influences how they seek care.

Conclusion
TB stigma contributes to suboptimal case finding and care at the community level in South Africa. Interventions to combat stigma, such as community and individual education campaigns on TB treatment and transmission as well as the training of health care workers on stigma and stigmatization are needed to prevent discrimination and protect patient confidentiality.