Miracle-dz/UniFAR-FTUs huggingface dataset:
Inter-surgeon variation in reoperation following strabismus surgery among Medicare beneficiaries: Associations with adjustable sutures, patient and surgeon characteristics.

Purpose: The objective of this study was to quantify inter-surgeon variation in strabismus surgery reoperation rates in a large national database of provider payments, and to explore associations of reoperation rate with practice type and volume, surgical techniques, and characteristics of the patient population. Methods: Fee-for-service payments to providers for Medicare beneficiaries having strabismus surgery between 2012 and 2020 were retrospectively analyzed to identify reoperations in the same calendar year. The adjustable-suture technique was considered to be available to the patient if the patient's surgeon billed for adjustable sutures. Predictors of the rate of reoperation for each surgeon were determined by multivariable linear regression. Results: Among 141 surgeons, the reoperation rate for 1-horizontal muscle surgery varied between 0.0% and 30.8%. Due to the presence of high-volume surgeons with high reoperation rates, just 11 surgeons contributed half of the reoperation events for 1-horizontal muscle surgery in this national database. Use of adjustable sutures, surgeon gender, and surgical volume were not independently associated with surgeon reoperation rate. Associations of reoperation with patient characteristics, such as age and poverty, were explored. In a multivariable model, surgeons in the South tended to have a higher reoperation rate (p=0.03). Still, the multivariable model could explain only 16.3% of the variation in surgeon reoperation rate for 1-horizontal muscle. For 1-vertical muscle surgery, patient poverty was associated with a lower surgeon reoperation rate (p=0.008). Conclusions: Patient-level analyses which ignore inter-surgeon variation will be dominated by the practices of a small number of high-volume, high-reoperation surgeons. There are order-of-magnitude variations in reoperation rates among strabismus surgeons, the cause of which remains largely unexplained.
PERCEPTION AND WILLINGNESS TO THE UPTAKE OF COVID-19 VACCINE AMONG HOUSEHOLD-HEADS IN A RURAL COMMUNITY OF SOUTH-WESTERN NIGERIA

Background: The COVID-19 pandemic and its vaccine have been met with varying perceptions that may have both negative and positive effects on the willingness to uptake the COVID-19 vaccine. The study is set to determine the perception and willingness of the household heads to the uptake of COVID-19 vaccine in a rural community in Southwestern, Nigeria. Materials and Methods: A cross-sectional study was carried out among 409 household heads selected through a multistage sampling technique. The instrument of data collection was a semi-structured interviewer-administered questionnaire using the Health Belief model constructs. Data were analyzed with IBM SPSS version 21.0 and Pearson’s Chi-square test was used to determine the association between perception and willingness to uptake vaccine. P<0.05 was taken as significant at 95% confidence interval. Results: The majority of the unvaccinated respondents in the study were not willing to take the COVID-19 vaccine (60.1%). There was a poor perception of the susceptibility/severity of unvaccinated respondents to COVID-19 infection and a poor perception of the benefit/barrier to the uptake of the COVID-19 vaccine. Perception of susceptibility and severity of COVID-19 infection were statistically related to the willingness to uptake the COVID-19 vaccine. Conclusion: There should be an increase in awareness campaigns to change the perception of people positively to COVID-19 infection and uptake of the COVID-19 vaccine.
Application of single-cell RNA sequencing on human testicular samples: a comprehensive review

So far there has been no comprehensive review using systematic literature search strategies to show the application of single-cell RNA sequencing (scRNA-seq) in the human testis of the whole life cycle (from embryos to aging males). Here, we summarized the application of scRNA-seq analyses on various human testicular biological samples. A systematic search was conducted in PubMed and Gene Expression Omnibus (GEO), focusing on English researches published after 2009. Articles related to GEO data-series were also retrieved in PubMed or BioRxiv. 81 full-length studies were finally included in the review. ScRNA-seq has been widely used on different human testicular samples with various library strategies, and new cell subtypes such as State 0 spermatogonial stem cells (SSC) and stage_a/b/c Sertoli cells (SC) were identified. For the development of normal testes, scRNA-seq-based evidence showed dynamic transcriptional changes of both germ cells and somatic cells from embryos to adults. And dysregulated metabolic signaling or hedgehog signaling were revealed by scRNA-seq in aged SC or Leydig cells (LC), respectively. For infertile males, scRNA-seq studies revealed profound changes of testes, such as the increased proportion of immature SC/LC of Klinefelter syndrome, the somatic immaturity and altered germline autophagy of patients with non-obstructive azoospermia, and the repressed differentiation of SSC in trans-females receiving testosterone inhibition therapy. Besides, the re-analyzing of public scRNA-seq data made further discoveries such as the potential vulnerability of testicular SARS-CoV-2 infection, and both evolutionary conservatism and divergence among species. ScRNA-seq analyses would unveil mechanisms of testes' development and changes so as to help developing novel treatments for male infertility.
Plasmodium falciparum-infected erythrocyte co-culture with the monocyte cell line THP-1 does not trigger production of soluble factors reducing brain microvascular barrier function

Monocytes contribute to the pro-inflammatory immune response during the blood stage of a Plasmodium falciparum infection, but their precise role in malaria pathology is not clear. Besides phagocytosis, monocytes are activated by products from P. falciparum infected erythrocytes (IE) and one of the activation pathways is potentially the NLR family pyrin domain containing 3 (NLRP3) inflammasome, a multi-protein complex that leads to the production of interleukin (IL)-1β. In cerebral malaria cases, monocytes accumulate at IE sequestration sites in the brain microvascular and the locally produced IL-1β, or other secreted molecules, could contribute to leakage of the blood-brain barrier. To study the activation of monocytes by IE within the brain microvasculature in an in vitro model, we co-cultured IT4var14 IE and the monocyte cell line THP-1 for 24 hours and determined whether generated soluble molecules affect barrier function of human brain microvascular endothelial cells, measured by real time trans-endothelial electrical resistance. The medium produced after co-culture did not affect endothelial barrier function and similarly no effect was measured after inducing oxidative stress by adding xanthine oxidase to the co-culture. While IL-1β does decrease barrier function, barely any IL-1β was produced in the co- cultures, indicative of a lack of or incomplete THP-1 activation by IE in this co-culture model.
Crohn’s disease proteolytic microbiota enhances inflammation through PAR2 pathway in gnotobiotic mice

ABSTRACT Emerging evidence implicates microbial proteolytic activity in ulcerative colitis (UC), but whether it also plays a role in Crohn’s disease (CD) remains unclear. We investigated the effects of colonizing adult and neonatal germ-free C57BL/6 mice with CD microbiota, selected based on high (CD-HPA) or low fecal proteolytic activity (CD-LPA), or microbiota from healthy controls with LPA (HC-LPA) or HPA (HC-HPA). We then investigated colitogenic mechanisms in gnotobiotic C57BL/6, and in mice with impaired Nucleotide-binding Oligomerization Domain-2 (NOD2) and Protease-Activated Receptor 2 (PAR2) cleavage resistant mice (Nod2 −/−; R38E-PAR2 respectively). At sacrifice, total fecal proteolytic, elastolytic, and mucolytic activity were analyzed. Microbial community and predicted function were assessed by 16S rRNA gene sequencing and PICRUSt2. Immune function and colonic injury were investigated by inflammatory gene expression (NanoString) and histology. Colonization with HC-LPA or CD-LPA lowered baseline fecal proteolytic activity in germ-free mice, which was paralleled by lower acute inflammatory cell infiltrate. CD-HPA further increased proteolytic activity compared with germ-free mice. CD-HPA mice had lower alpha diversity, distinct microbial profiles and higher fecal proteolytic activity compared with CD-LPA. C57BL/6 and Nod2 −/− mice, but not R38E-PAR2, colonized with CD-HPA had higher colitis severity than those colonized with CD-LPA. Our results indicate that CD proteolytic microbiota is proinflammatory, increasing colitis severity through a PAR2 pathway.
Targeting macrophage autophagy for inflammation resolution and tissue repair in inflammatory bowel disease

Abstract Inflammatory bowel disease (IBD) is a chronic, non-specific, recurrent inflammatory disease, majorly affecting the gastrointestinal tract. Due to its unclear pathogenesis, the current therapeutic strategy for IBD is focused on symptoms alleviation. Autophagy is a lysosome-mediated catabolic process for maintaining cellular homeostasis. Genome-wide association studies and subsequent functional studies have highlighted the critical role of autophagy in IBD via a number of mechanisms, including modulating macrophage function. Macrophages are the gatekeepers of intestinal immune homeostasis, especially involved in regulating inflammation remission and tissue repair. Interestingly, many autophagic proteins and IBD-related genes have been revealed to regulate macrophage function, suggesting that macrophage autophagy is a potentially important process implicated in IBD regulation. Here, we have summarized current understanding of macrophage autophagy function in pathogen and apoptotic cell clearance, inflammation remission and tissue repair regulation in IBD, and discuss how this knowledge can be used as a strategy for IBD treatment.
Cytochalasin D restores nuclear size acting on F-actin and IZUMO1 localization in low-quality spermatozoa

In spermatozoa, the nuclear F-actin supports the acroplaxome, a subacrosomal structure involved in the correct exposure of several acrosomal membrane proteins; among them, the glycoprotein IZUMO1 is the major protein involved in sperm-oocyte fusion. Nuclear F-actin is also involved in sperm head shaping and chromosome compartmentalization. To date, few notions regarding the bivalent role of F-actin on sperm chromatin organization and IZUMO1 positioning have been reported. In our work, we characterized subcellular organization of F-actin in human high- and low-quality spermatozoa (A- and B-SPZ), respectively, showing that F-actin over-expression in sperm head of B-SPZ affected IZUMO1 localization. A correct IZUMO1 repositioning following in vitro induction of F-actin depolymerization, by cytochalasin D treatment, occurred. Interestingly, F-actin depolymerization was also associated with a correct acrosome repositioning, thus to favor a proper acrosome reaction onset, with changes in sperm nuclear size parameters and histone acetylation rate reaching high-quality conditions. In conclusion, the current work shows a key role of F-actin in the control of IZUMO1 localization as well as chromatin remodeling and acetylation events.
Do statins enhance the antitumor effect of trastuzumab emtansine (T-DM1)?: Real-life cohort

Human epidermal growth factor receptor 2 (HER2)-targeting therapies have become crucial in the management of HER2-positive breast cancer. Trastuzumab emtansine (T-DM1) is a microtubule inhibitor and HER2-targeted antibody conjugate. T-DM1 resistance is most likely influenced by factors involved in the biological mechanisms of T-DM1 action. This study aimed to examine the efficacy of statins, which influence HER-2-based therapies via the caveolin-1 (CAV-1) protein, in female breast cancer patients receiving T-DM1. Our study included 105 patients with HER2-positive metastatic breast cancer treated with T-DM1. The progression-free survival (PFS) and overall survival (OS) of patients who received statins concurrently with T-DM1 versus those who did not were compared. During the median 39.5 (95% confidence interval [CI]: 35.6–43.5) months of follow-up, 16 (15.2%) patients received statins, and 89 (84.8%) patients did not. Median OS was significantly higher in patients using statins than in patients not using statins (58.8 vs 26.5 months, P = .016). The association between statin use and PFS did not reach statistical significance (34.7 vs 9.9 months, P = .159). Multivariate Cox regression analysis showed that better performance status (hormone receptor [HR]: 0.30, 95% CI: 0.13–0.71, P = .006), use of trastuzumab plus pertuzumab prior to T-DM1 (HR: 0.37, 95% CI: 0.18–0.76, P = .007) and use of statins with T-DM1 (HR: 0.29, 95% CI: 0.12–0.70, P = .006) were independent factors that prolong OS duration. Our study showed that T-DM1 is more effective at treating HER2-positive breast cancer in people who receive statins concurrently with T-DM1 than those who do not.
ASSOCIATION OF BLOOD TYPE AND MORTALITY OF COVID-19: A HOSPITAL-BASED STUDY IN NATIONAL REFERRAL HOSPITAL, INDONESIA

Background: The ABO blood type is crucial in a number of illnesses, including cancer, cardiovascular disease, and some communicable and non-communicable illnesses. However, there is currently little clear evidence between COVID-19 with ABO blood types. This study was, therefore, aimed to assess the association between ABO blood type and the mortality of patients infected with COVID-19 in a national referral hospital in Indonesia. Materials and Methods: This study used a retrospective cohort design. The research sample was COVID-19 patients who were in Dr. M. Djamil Hospital Padang. The number of samples in this study was 93 subjects. The Chi-square test was used in the data analysis. The data were analyzed using the SPSS version 21.0 program, and p<0.05 was considered significant. Results: The results of this study found the percentage of mortality of COVID-19 patients was higher for blood group O (46.2%), followed by AB (41.7%), B (26.3%), and A (13.9%). There was a relationship between blood type and mortality in hospitalized COVID-19 patients (p <0.05), where blood type O had the highest risk (OR = 5.31, 95% CI 1.57-17.98) followed by blood type AB (OR = 4.43, 95% CI 1.01-19.58). Conclusion: This study confirmed there was a relationship between blood type and mortality in hospitalized COVID-19 patients, where blood type O had the highest risk followed by blood type AB.
OTUD1 promotes pathological cardiac remodeling and heart failure by targeting STAT3 in cardiomyocytes

Rationale: Understanding the molecular mechanisms of deleterious cardiac remodeling is important for the development of treatments for heart failure. Recent studies have highlighted a role of deubiquitinating enzymes in cardiac pathophysiology. In the present study, we screened for alteration of deubiquitinating enzymes in experimental models of cardiac remodeling, which indicated a potential role of OTU Domain-Containing Protein 1 (OTUD1). Methods: Wide-type or OTUD1 knockout mice with chronic angiotensin II infusion and transverse aortic constriction (TAC) were utilized to develop cardiac remodeling and heart failure. We also overexpressed OTUD1 in mouse heart with AAV9 vector to validate the function of OTUD1. LC-MS/MS analysis combined with Co-IP was used to identify the interacting proteins and substrates of OTUD1. Results: We found that OTUD1 is elevated in mouse heart tissues following chronic angiotensin II administration. OTUD1 knockout mice were significantly protected against angiotensin II-induced cardiac dysfunction, hypertrophy, fibrosis and inflammatory response. Similar results were obtained in the TAC model. Mechanistically, OTUD1 bounds to the SH2 domain of STAT3 and causes deubiquitination of STAT3. Cysteine at position 320 of OTUD1 exerts K63 deubiquitination to promote STAT3 phosphorylation and nuclear translocation, thereby increasing STAT3 activity to induce inflammatory responses, fibrosis, and hypertrophy in cardiomyocytes. Finally, OTUD1 overexpression by AAV9 vector increases Ang II-induced cardiac remodeling in mice and OTUD1-regulated responses can be inhibited by blocking STAT3. Conclusion: Cardiomyocyte OTUD1 promotes pathological cardiac remodeling and dysfunction by deubiquitinating STAT3. These studies have highlighted a novel role of OTUD1 in hypertensive heart failure and identified STAT3 as a target of OTUD1 in mediating these actions.
Incidence of hospital acquired pressure injury in critically ill patients with COVID-19 in prone position admitted to the intensive care unit

Critical patients have conditions that may favor the occurrence of hospital-acquired pressure injury (HAPI). The objective of this study was to identify the incidence and factors associated with the occurrence of HAPI in patients with coronavirus disease 2019 admitted to the intensive care unit (ICU) who used the prone position. Retrospective cohort study carried out in an ICU of a tertiary university hospital. Two hundred four patients with positive real-time polymerase chain reactions were evaluated, of which 84 were placed in the prone position. All patients were sedated and submitted to invasive mechanical ventilation. Of the prone patients, 52 (62%) developed some type of HAPI during hospitalization. The main place of occurrence of HAPI was the sacral region, followed by the gluteus and thorax. Of the patients who developed HAPI, 26 (50%) had this event in places possibly associated with the prone position. The factors associated with the occurrence of HAPI in patients prone to coronavirus disease 2019 were the Braden Scale and the length of stay in the ICU. The incidence of HAPI in prone patients was extremely high (62%), which denotes the need to implement protocols in order to prevent the occurrence of these events.
Youth-to-senior transition in women’s and girls’ football: Towards a better understanding of relative age effects and gender-specific considerations

This study aimed to evaluate youth-to-senior transition and the relative age effect in Italian female football national teams. Birthdate data of 774 female players selected for Under 17 (N = 416), 19 (N = 265) and National Senior team (N = 93) were analysed. The youth-to-senior transition rate was determined by the number of youth players competing in the Senior National team (and vice versa), whilst birth quarter (Q) distributions with a chi-square goodness-of-fit test. Only 17.4% of youth players were able to be selected for the Senior National team, whereas 31.2% of the players reached the high-senior level without being selected for youth age groups. Data revealed a skewed birth date distribution in Under 17 and 19 teams (on average, Q1 = 35.6% vs Q4 = 18.5%) but not in the Senior National team. Youth players born in Q1 were two times more likely to be selected than in Q4. In Under 17, goalkeepers, defenders, and midfielders of Q1 players were overrepresented. However, Q4 players recorded higher conversion rates than Q1 (Q1 = 16.4% vs. Q4 = 25.0%). National youth experience may not be a prerequisite for being selected at the senior level. Moreover, this confers a higher probability of playing in the National Senior team than players not selected in youth rosters.
Self-warming blankets versus active warming by forced-air devices for preventing hypothermia: A systematic review and meta-analysis

Background: Unintended perioperative hypothermia is a significant complication for patients undergoing anesthesia. Different measures are routinely undertaken to prevent hypothermia and its consequences. The evidence comparing the impact of self-warming blankets and forced-air warming is scarce. Therefore, this meta-analysis aimed to evaluate the efficacy of self-warming blankets compared to forced-air devices regarding the incidence of perioperative hypothermia. Methods: We searched the Web of Science, Cochrane Central Register of Controlled Trials, PubMed, and Scopus for relevant studies from inception until December 2022. We included comparative studies with patients allocated to undergo warming using a self-warming blanket or forced air warming. All concerned outcomes were pooled as odds ratios or mean differences (MDs) in the meta-analysis models using Review Manager (RevMan version 5.4). Results: Our results from 8 studies (597 patients) favored self-warming blankets over forced-air devices in terms of core temperature at 120 and 180 minutes after induction of general anesthesia (MD = 0.33, 95% confidence interval [CI] [0.14–0.51], P = .0006), (MD = 0.62, 95% CI [0.09–1.14], P = .02), respectively. However, the overall effect did not favor either of the 2 groups for the incidence of hypothermia (odds ratio = 0.69, 95% CI [0.18–2.62]). Conclusion: Ultimately, self-warming blankets have a more significant effect than forced-air warming systems in terms of maintaining normothermia of core temperature after induction anesthesia. However, the present evidence is not enough to verify the efficacy of the 2 warming techniques in the incidence of hypothermia. Further studies with large sample sizes are recommended.
Unidirectional fluxes of monovalent ions in human erythrocytes compared with lymphoid U937 cells: Transient processes after stopping the sodium pump and in response to osmotic challenge

Recently, we have developed software that allows, using a minimum of required experimental data, to find the characteristics of ion homeostasis and a list of all unidirectional fluxes of monovalent ions through the main pathways in the cell membrane both in a balanced state and during the transient processes. Our approach has been successfully validated in human proliferating lymphoid U937 cells during transient processes after stopping the Na/K pump by ouabain and for staurosporine-induced apoptosis. In present study, we used this approach to find the characteristics of ion homeostasis and the monovalent ion fluxes through the cell membrane of human erythrocytes in a resting state and during the transient processes after stopping the Na/K pump with ouabain and in response to osmotic challenge. Due to their physiological significance, erythrocytes remain the object of numerous studies, both experimental and computational methods. Calculations showed that, under physiological conditions, the K+ fluxes through electrodiffusion channels in the entire erythrocyte ion balance is small compared to the fluxes through the Na/K pump and cation–chloride cotransporters. The proposed computer program well predicts the dynamics of the erythrocyte ion balance disorders after stopping the Na/K pump with ouabain. In full accordance with predictions, transient processes in human erythrocytes are much slower than in proliferating cells such as lymphoid U937 cells. Comparison of real changes in the distribution of monovalent ions under osmotic challenge with the calculated ones indicates a change in the parameters of the ion transport pathways through the plasma membrane of erythrocytes in this case. The proposed approach may be useful in studying the mechanisms of various erythrocyte dysfunctions.