bluuebunny/crossref_metadata_2025 huggingface dataset:
IL-7 receptor signaling drives human B-cell progenitor differentiation and expansion
Authors: Kaiser Fabian M. P. , Janowska Iga , Menafra Roberta , de Gier Melanie , Korzhenevich Jakov , Pico-Knijnenburg Ingrid , Khatri Indu , Schulz Ansgar , Kuijpers Taco W. , Lankester Arjan C. , Konstantinidis Lukas , Erlacher Miriam , Kloet Susan , van Schouwenburg Pauline A. , Rizzi Marta , van der Burg Mirjam
Published: June 2023

Although absence of interleukin-7 (IL-7) signaling completely abrogates T and B lymphopoiesis in mice, patients with severe combined immunodeficiency caused by mutations in the IL-7 receptor α chain (IL-7Rα) still generate peripheral blood B cells. Consequently, human B lymphopoiesis has been thought to be independent of IL-7 signaling. Using flow cytometric analysis and single-cell RNA sequencing of bone marrow samples from healthy controls and patients who are IL-7Rα deficient, in combination with in vitro modeling of human B-cell differentiation, we demonstrate that IL-7R signaling plays a crucial role in human B lymphopoiesis. IL-7 drives proliferation and expansion of early B-cell progenitors but not of pre-BII large cells and has a limited role in the prevention of cell death. Furthermore, IL-7 guides cell fate decisions by enhancing the expression of BACH2, EBF1, and PAX5, which jointly orchestrate the specification and commitment of early B-cell progenitors. In line with this observation, early B-cell progenitors of patients with IL-7Rα deficiency still expressed myeloid-specific genes. Collectively, our results unveil a previously unknown role for IL-7 signaling in promoting the B-lymphoid fate and expanding early human B-cell progenitors while defining important differences between mice and humans. Our results have implications for hematopoietic stem cell transplantation strategies in patients with T− B+ severe combined immunodeficiency and provide insights into the role of IL-7R signaling in leukemogenesis.
Use of a taxon-specific reference database for accurate metagenomics-based pathogen detection of Listeria monocytogenes in turkey deli meat and spinach
Authors: Rumore Jillian , Walker Matthew , Pagotto Franco , Forbes Jessica D. , Peterson Christy-Lynn , Tyler Andrea D. , Graham Morag , Van Domselaar Gary , Nadon Celine , Reimer Aleisha , Knox Natalie
Published: June 2023

Background

The reliability of culture-independent pathogen detection in foods using metagenomics is contingent on the quality and composition of the reference database. The inclusion of microbial sequences from a diverse representation of taxonomies in universal reference databases is recommended to maximize classification precision for pathogen detection. However, these sizable databases have high memory requirements that may be out of reach for some users. In this study, we aimed to assess the performance of a foodborne pathogen (FBP)-specific reference database (taxon-specific) relative to a universal reference database (taxon-agnostic). We tested our FBP-specific reference database's performance for detecting Listeria monocytogenes in two complex food matrices—ready-to-eat (RTE) turkey deli meat and prepackaged spinach—using three popular read-based DNA-to-DNA metagenomic classifiers: Centrifuge, Kraken 2 and KrakenUniq.

Results

In silico host sequence removal led to substantially fewer false positive (FP) classifications and higher classification precision in RTE turkey deli meat datasets using the FBP-specific reference database. No considerable improvement in classification precision was observed following host filtering for prepackaged spinach datasets and was likely a consequence of a higher microbe-to-host sequence ratio. All datasets classified with Centrifuge using the FBP-specific reference database had the lowest classification precision compared to Kraken 2 or KrakenUniq. When a confidence-scoring threshold was applied, a nearly equivalent precision to the universal reference database was achieved for Kraken 2 and KrakenUniq. Recall was high for both reference databases across all datasets and classifiers. Substantially fewer computational resources were required for metagenomics-based detection of L. monocytogenes using the FBP-specific reference database, especially when combined with Kraken 2.

Conclusions

A universal (taxon-agnostic) reference database is not essential for accurate and reliable metagenomics-based pathogen detection of L. monocytogenes in complex food matrices. Equivalent classification performance can be achieved using a taxon-specific reference database when the appropriate quality control measures, classification software, and analysis parameters are applied. This approach is less computationally demanding and more attainable for the broader scientific and food safety communities.
MiR-196b-3p and miR-450b-3p are key regulators of adipogenesis in porcine intramuscular and subcutaneous adipocytes
Authors: Wu Wenjing , Liu Keke , You Zhongyu , Zhang Jin
Published: June 2023

Background

As components of white adipose tissue, porcine intramuscular (IM) and subcutaneous (SC) adipocytes undergo similar differentiation and adipogenesis processes. However, the adipogenic capacity of IM adipocytes is weaker than that of SC adipocytes. Identifying key regulators underlying this difference between IM and SC adipocytes will benefit pig breeding.

Results

In this study, we used BGISEQ-500 sequencing technology to analyze the expression of small RNAs in primary cultured IM and SC adipocytes on day 8 after adipogenic induction, and found 32-fold higher miR-196b-3p expression, as well as 8-fold lower miR-450b-3p expression in IM adipocytes than in SC adipocytes. Functional studies revealed that miR-196b-3p inhibits adipogenesis by targeting CD47 via the AMPK signaling pathway, and its effect was attenuated by the specific p-AMPKα activator AICAR. We also found that miR-450b-3p promotes adipogenesis by targeting SIRT1 via the Wnt/β-catenin signaling pathway, and its effect was weakened by the Wnt/β-catenin signaling activator LiCl.

Conclusions

Our findings suggest that miR-196b-3p and miR-450b-3p are novel key regulatory factors that play opposite roles in porcine adipogenesis, helping us decipher the regulatory differences between porcine IM and SC fat deposition.
SGLT2 inhibitors can reduce the incidence of abnormal blood glucose caused by statins in non-diabetes patients with HFrEF after PCI
Authors: Yang Yulin , Wang Xiaolin , Wang Yongchao , Xu Hao , Li Jian
Published: June 2023

Background

Taking statins for a long time is associated with an increased risk of new-onset diabetes mellitus. Sodium-glucose cotransporter-2 (SGLT2) inhibitors can reduce insulin resistance and improve pancreatic β-cell function.

Methods and results

In total, 333 non-diabetes patients with heart failure with reduced ejection fraction (HFrEF) after percutaneous coronary intervention (PCI) are included. The enrolled patients are divided into a matched group (n = 198) and an SGLT2 inhibitors group (n = 135). There are no statistical differences in general information between the two groups before treatment. After a mean follow-up time of 13 months, abnormal blood glucose levels are significantly higher in the matched group than in the SGLT2 inhibitors group (6.06 vs. 0.74%, P < 0.05). There are no statistically significant differences in the alanine aminotransferase (ALT), uric acid (UA), and estimated glomerular filtration (eGFR) levels between the two groups.

Conclusion

SGLT2 inhibitors play a significant protective role in reducing the risk of statins-induced abnormal blood glucose in non-diabetes patients with HFrEF after PCI, without increasing the burden on the heart, kidneys, and liver.
Computed tomography findings in patients with pulmonary tuberculosis and diabetes at an infectious disease hospital in China: a retrospective cross-sectional study
Authors: Yang Qianwen , Zhang Rongping , Gao Yan , Zhou Chaoxin , Kong Weifang , Tao Wang , Zhang Guojin , Shang Lan
Published: June 2023

Background

This study aimed to investigate the relationship between active pulmonary tuberculosis (TB) and type 2 diabetes mellitus (T2DM) by analysing the clinical features and computed tomography (CT) findings of patients with active pulmonary TB and comorbid T2DM (TB-DM) in the LiangShan Yi regions.

Methods

We collected data from 154 hospitalised patients with TB-DM initially confirmed at an infectious disease hospital in the Liangshan Yi Autonomous Prefecture between 1 and 2019, and 31 December 2021. These were matched by sex and age ± 3 years to 145 hospitalised patients with initially confirmed pulmonary TB without comorbid T2DM (TB-NDM) over the same period. The clinical characteristics of the two groups were analysed separately. Three group-blinded radiologists independently analysed the CT findings and classified them into mild-to-moderate and severe groups. Severe chest CT lesion refers to a lesion that is less diffused or moderately dense and either exceeds the total volume of one lung, a high-density fused lesion greater than one-third of the volume of one lung, or a cavitary lesion with a maximum diameter ≥ 4 cm.

Results

No significant differences were observed in the presentation of clinical features. Regarding the severity of chest CT manifestation, patients with TB-DM had significantly more severe TB than those with TB-NDM (89.61% vs. 68.97%, P < 0.0001). Regarding CT findings, patients with TB-DM had higher proportions of consolidation (79.22% vs. 52.41%, P < 0.0001), cavitary lesions (85.06% vs. 59.31%, P < 0.0001), bronchiectasis (71.43% vs. 31.03%, P < 0.0001), exudative lesions (88.96% vs. 68.28%, P < 0.0001), and fibrous lesions (93.51% vs. 68.97%, P < 0.0001) than patients with TB-NDM. In conclusion, patients with TB-DM have more severe pulmonary TB CT findings than those without. There were no significant differences in the distribution of lesions in the lung lobes between TB-DM and TB-NDM patients.

Conclusions

Among patients hospitalised with pulmonary TB, those with T2DM had more severe findings on chest CT than those without T2DM. However, the clinical presentation was not significantly different.
Molecular characterisation of human adenoviruses associated with respiratory infections in Uganda
Authors: Ukuli Qouilazoni A. , Erima Bernard , Mubiru Andrew , Atim Gladys , Tugume Titus , Kibuuka Hannah , Mworozi Edison , Ducatez Mariette F. , Wabwire-Mangen Fred , Byarugaba Denis K.
Published: June 2023

Human adenoviruses (HAdV) are a diverse group of viruses causing a broad range of infections of the respiratory, urogenital and gastrointestinal tracts and keratoconjunctivitis. There are seven species of human adenoviruses with 113 genotypes which may contain multiple genetic variants. This study characterised respiratory human adenoviruses and associated factors in samples collected from selected hospitals in Uganda. A total of 2,298 nasopharyngeal samples were collected between the period of 2008 to 2016 from patients seeking health care at tertiary hospitals for influenza-like illness. They were screened by polymerase chain reaction (PCR) to determine the prevalence of HAdV. HAdV was cultured in A549 cell lines and the hexon gene was sequenced for genotyping. Of the 2,298 samples tested, 225 (9.8%) were adenovirus-positive by PCR. Age was found to be significantly associated with HAdV infections (p = 0.028) with 98% (220/225) of the positives in children aged 5 years and below and none in adults above 25 years of age. The sequenced isolates belonged to species HAdV-B and HAdV-C with most isolates identified as genotype B3. The results showed a high prevalence and genetic diversity in respiratory HAdV circulating in Ugandan population. Deeper genomic characterization based on whole genome sequencing may be necessary to further elucidate possible transmission and impact of current adenovirus-vectored vaccines in Africa.
Construction of the machine learning-based live birth prediction models for the first in vitro fertilization pregnant women
Authors: Liu Xiaoyan , Chen Zhiyun , Ji Yanqin
Published: June 2023

Background

This study was to conduct prediction models based on parameters before and after the first cycle, respectively, to predict live births in women who received fresh or frozen in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) for the first time.

Methods

This retrospective cohort study population consisted of 1,857 women undergoing the IVF cycle from 2019 to 2021 at Huizhou Municipal Central Hospital. The data between 2019 and 2020 were completely randomly divided into a training set and a validation set (8:2). The data from 2021 was used as the testing set, and the bootstrap validation was carried out by extracting 30% of the data for 200 times on the total data set. In the training set, variables are divided into those before the first cycle and after the first cycle. Then, predictive factors before the first cycle and after the first cycle were screened. Based on the predictive factors, four supervised machine learning algorithms were respectively considered to build the predictive models: logistic regression (LR), random forest (RF), extreme gradient boosting (XGBoost), and light gradient boosting machine (LGBM). The performances of the prediction models were evaluated by the area under the receiver operator characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy.

Results

Totally, 851 women (45.83%) had a live birth. The LGBM model showed a robust performance in predicting live birth before the first cycle, with AUC being 0.678 [95% confidence interval (CI): 0.651 to 0.706] in the training set, 0.612 (95% CI: 0.553 to 0.670) in the validation set, 0.634 (95% CI: 0.511 to 0.758) in the testing set, and 0.670 (95% CI: 0.626 to 0.715) in the bootstrap validation. The AUC value in the training set, validation set, testing set, and bootstrap of LGBM to predict live birth after the first cycle was 0.841 (95% CI: 0.821 to 0.861), 0.816 (95% CI: 0.773 to 0.859), 0.835 (95% CI: 0.743 to 0.926), and 0.839 (95% CI: 0.806 to 0.871), respectively.

Conclusion

The LGBM model based on the predictive factors before and after the first cycle for live birth in women showed a good predictive performance. Therefore, it may assist fertility specialists and patients to adjust the appropriate treatment strategy.
Ntombi Vimbela! Sexual violence risk reduction intervention: pre and one-year post assessments from a single arm pilot feasibility study among female students in South Africa
Authors: Machisa Mercilene Tanyaradzwa , Mahlangu Pinky , Chirwa Esnat , Nunze Ncediswa , Sikweyiya Yandisa , Dartnall Elizabeth , Pillay Managa , Jewkes Rachel
Published: June 2023

Background

The extremely high prevalence of sexual violence victimisation reported among female students in South African public higher education demands urgent action to develop, rigorously evaluate and scale effective prevention interventions. This article details findings from a pilot feasibility study of Ntombi Vimbela! a campus sexual violence risk reduction intervention developed to tackle the high burden of sexual violence in higher education institutions in South Africa.

Methods

Ntombi Vimbela! (NV!) is a sexual violence risk reduction intervention that comprises sexuality empowerment, gender and social norm change, early-risk identification, self-defence, resistance and mental wellbeing components. NV! is comprised of ten workshop sessions running for 3.5 h each. Workshops are co-delivered by two trained peer facilitators per group of at most 20 first-year female students. One-year post-intervention quantitative outcome assessments were remotely completed by 98 participants who participated in the NV! pilot workshops. Qualitative assessments were conducted with 35 participants through in-depth telephone interviews (IDTIs).

Findings

One year after attending NV! workshops, most participants reported improved awareness of sexual rights, assertive communication, shifts in gender equitable beliefs, reductions in rape myth acceptance, improved expressed sexual relationship power sexual decision-making, and improved negotiation within their intimate relationships. Participants’ depressive symptoms also significantly decreased. Many participants improved awareness of sexual assault risk and vigilance, including using self-protection strategies such as removing themselves from environments where alcohol intoxication posed sexual assault risks. Some participants used assertive communication to withstand peer pressure to engage in risky sexual behaviours. Most participants scored highly on the self-defence efficacy scale. Some participants were exposed to and successful in using verbal and physical resistance strategies in potential sexual assault risky situations.

Conclusion

These findings indicate the potential beneficial effects of NV! as a campus sexual violence risk reduction intervention at one-year post-intervention, which must be evaluated in a future rigorous randomised control trial.

Pilot trial registered at

ClinicalTrials.gov NCT04607564 on 29/10/2020.
Esophageal perforation etiology, outcome, and the role of surgical management – an 18-year experience of surgical cases in a referral center
Authors: Shahriarirad Reza , Karoobi Mohamadreza , Shekouhi Ramin , Ebrahimi Kamyar , Ranjbar Keivan , Amirian Armin , Mardani Parviz , Fallahi Mohammad Javad , Ziaian Bizhan
Published: June 2023

Introduction

Esophageal perforation is a surgical emergency with a high rate of morbidity and mortality. Its poor prognosis is mainly associated with previous patient-specific comorbidities and a lack of timely diagnosis and treatment. The objective of this study was to investigate the etiological factors and different surgical methods of treatment with consideration of mortality rate and comorbidities.

Method

The present cross-sectional study was conducted on patients who underwent surgical intervention due to esophageal injury from 2002 to 2019 (18 years). Demographic and clinical characteristics along with performed surgical interventions were evaluated accordingly.

Results

In this study, 69 patients with a mean age of 38.8 years were evaluated, of which 45 (65.2%) cases were men. In terms of location of the perforation, the thoracic portion of the esophagus followed by the cervical and abdominal esophagus were more frequently injured with a rate of 32 (46.4%), 30 (43.5%), and 19 (27.5%) cases, respectively. Accordingly, foreign body ingestion followed by penetrating injuries were the most common causative agents leading to esophageal perforation.

Conclusion

Obtaining the desired results from the treatment of this condition depends on factors such as patients’ previous comorbidities, cause of the rupture, the location of the esophageal damage, and delay in the start of treatment. Since there is no single gold standard treatment strategy, each patient should be individually evaluated.
Endophytic upper tract urothelial carcinoma in a solitary kidney treated by cryotherapy: an unorthodox case for successful management
Authors: Abdelaziz Ahmad , Sultan Mark , Hammad Muhammed A , Martinez Juan Ramon , Yacoub Maria , Youssef Ramy F
Published: June 2023

Background

Nephroureterectomy remains the gold standard treatment for upper tract urothelial carcinoma (UTUC). Considering the high risk of developing renal function impairment after surgery, the rationale for nephron sparing approaches in treatment of UTUC has been raised. In this case, renal cryoablation was able to achieve successful oncologic control while preserving renal function during 5 years of follow up without intraoperative or post operative complications.

Case presentation

A 79 year old male presents after three months of macroscopic hematuria. Imaging revealed a 3.6 × 3.1 × 2.7 cm endophytic mass in the interpolar region of the left kidney and an atrophic right kidney. After weighing the lesion’s location with the patient’s of complex medical history, he was counselled to undergo a minimally invasive percutaneous cryoablation as treatment for his solitary renal mass. A diagnostic dilemma was encountered as imaging suggested a diagnosis of renal cell carcinoma. However, the pre-ablation biopsy established an alternative diagnosis, revealing UTUC. Percutaneous cryoablation became an unorthodox treatment modality for the endophytic component of his UTUC followed by retrograde ureteroscopic laser fulguration. The patient was followed in 3 months, 6 months, then annually with cross sectional imaging by MRI, cystoscopy, urine cytology and renal function testing. After five years of follow-up, the patient did not encountered recurrence of UTUC or deterioration in renal function, thereby maintaining a stable eGFR.

Conclusion

Although evidence for nephron-sparing modalities for UTUC is mounting in recent literature, limited data still exists on cryotherapy as a line of treatment for urothelial carcinoma. We report successful management of a low-grade UTUC using cryoablation with the crucial aid of an initial renal biopsy and long-term follow-up. Our results provide insight into the role of cryoablation as a nephron-sparing approach for UTUC.
Effectiveness of the Positive Youth Development (PYD) Program on reducing aggression among high school female students
Authors: Zareei mahmoodabadi z Hassan , ebrahimi Asieh , Sooreshjani Razieh Heydari
Published: June 2023

Background

The positive youth development program highlights the abilities of adolescents and young people. This concept emphasizes that teenagers are capable of making positive changes (such as: flexibility, Responsibility, Identify abilities). This study aimed to determine the effectiveness of the Positive Youth Development (PYD) program on reducing aggression among high school female students in Yazd city. Iran.

Methods

This was a quasi-experimental study, using pretest-posttest design with a control group. In the 2019–2020 academic year, the statistical population comprised all female students in high school first and second years in the city of Yazd, Iran. Using purposive sampling and based on include and exclude criteria (high risk of aggression due to their scores on a screening test and Parental consent to participate in the class) 30 female students were selected. Randomly, they were assigned to an experimental(n = 15) and control groups(n-15). The Buss-Perry Aggression Questionnaire was conducted on students. The experimental group had 8 intervention sessions, whereas the control group received no intervention. The data were subsequently examined using Analysis of Covariance(ANCOVA).

Results

The dependent t-test revealed a significant difference between the pretest-posttest aggression scores in the experimental group, but there was no significant difference in the control group. There was no significant difference in the mean scores of physical aggression, anger, and hostility in the experimental and control groups, but a significant difference was found between the experimental and control groups in the mean verbal aggression scores.

Conclusion

training of positive youth development did not affect on aggression and its three dimensions (physical aggression, anger, and hostility) and only affected adolescent verbal aggression.
Promising score for teaching and learning environment: an experience of a fledgling medical college in Saudi Arabia
Authors: Almansour Mohammed , AlMehmadi Bader A. , Zeb Nida Gulzar , Matbouly Ghassan , Sami Waqas , Badahdah Al-Mamoon
Published: June 2023

Background

Professional competency of graduates of an institute reflects its teaching and learning environment (TLE). This study aimed to provide a preliminary assessment of the TLE at the College of Medicine at Majmaah University.

Methods

A cross-sectional survey was conducted during the 2019-20 academic year among students at the College. A validated scoring tool “the Experience of Teaching and Learning Questionnaire” (available at https://bit.ly/3sVBuEw) was used. The mean score of each section and statement, the difference between the mean scores of different demographic groups, and correlations between sections were analysed.

Results

A total of 234 (72.2%) enrolled students participated in this survey, with a male-to-female ratio and a ratio of participants from basic to clinical years being 2:1 and 1:1, respectively. Most participants reported a GPA of above 3/5. The overall mean score was 3.52/5 points. Section one “approaches to learning and studying” has the highest mean score (3.68), and no section scored a mean below three, though section three “demands made by the course” scored a borderline mean of 3.08. Students in clinical years had a significantly higher overall mean score compared to their counterparts (3.66 vs. 3.39, p < 0.001).

Conclusions

Students at the College had a positive perception of the TLE, but face challenges in coping with the demands of acquiring knowledge and subject-based skills, and in appreciating the TLE especially during basic science years, highlighting the need for an atmosphere that allows them to meet demands and develop greater appreciation.
Learning for doctor-to-doctor collaboration: a qualitative study exploring the experiences of residents and supervisors with intraprofessional workplace learning in complex tertiary care
Authors: Teheux Lara , Wollaars Hanna , Draaisma Jos M.T. , Coolen Ester H.A.J. , Kuijer-Siebelink Wietske , van der Velden Janiëlle A.E.M.
Published: June 2023

Background

To deliver high-quality care for individuals with complex medical conditions, residents need to be trained across the boundaries of their specialties. This study aimed to explore learning activities and influencing factors in intraprofessional workplace learning by residents in complex tertiary care.

Methods

This qualitative study was conducted in a tertiary care children’s hospital. In September – December 2017, fourteen individual and two focus group interviews were conducted with a purposive sample of residents and supervisors of various specialties. Transcribed interviews were thematically analyzed to describe learning activities and influencing factors that play a role in intraprofessional workplace learning in complex tertiary care settings during residency training.

Results

Respondents described numerous activities that they considered opportunities for intraprofessional learning, both directly and not directly related to patient care. However, deliberate attention to intraprofessional learning often seemed to be lacking in clinical practice. Influencing factors on a system (macro), organization (meso) and personal and interpersonal level (micro) level were identified. Factors on the macro and meso level mainly determined whether intraprofessional learning opportunities arose, while micro level factors mainly influenced whether opportunities were seized.

Conclusions

There are ample opportunities for intraprofessional workplace learning in complex tertiary care for residents. Residents may benefit more from intraprofessional learning opportunities if these are made more intentional and deliberate. Influencing factors at the macro, meso and micro level provide targets for interventions aimed at enhancing intraprofessional workplace learning in postgraduate medical training.
Identification of molecular subgroups in osteomyelitis induced by staphylococcus aureus infection through gene expression profiles
Authors: Shi Xiangwen , Ni Haonan , Tang Linmeng , Li Mingjun , Wu Yipeng , Xu Yongqing
Published: June 2023

Background

Staphylococcus aureus (S. aureus) infection-induced osteomyelitis (OM) is an inflammatory bone disease accompanied by persistent bone destruction, and the treatment is challenging because of its tendency to recur. Present study was aimed to explore the molecular subgroups of S. aureus infection-induced OM and to deepen the mechanistic understanding for molecularly targeted treatment of OM.

Methods

Integration of 164 OM samples and 60 healthy samples from three datasets of the Gene Expression Omnibus (GEO) database. OM patients were classified into different molecular subgroups based on unsupervised algorithms and correlations of clinical characteristics between subgroups were analyzed. Next, The CIBERSORT algorithm was used to evaluate the proportion of immune cell infiltration in different OM subgroups. Weighted gene co-expression analysis (WGCNA) was used to identify different gene modules and explore the relationship with clinical characteristics, and further annotated OM subgroups and gene modules by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.

Results

Two subgroups with excellent consistency were identified in this study, subgroup and hospital length of stay were independent predictors of OM. Compared with subgroup I, OM patients in subgroup II had longer hospital length of stay and more severe disease. Meanwhile, the infiltration proportions of monocytes and macrophages M0 were higher in patients of OM subgroup II. Finally, combined with the characteristics of the KEGG enrichment modules, the expression of osteoclast differentiation-related genes such as CTSK was upregulated in OM subgroup II, which may be closely associated with more severe OM patients.

Conclusion

The current study showed that OM subgroup II had longer hospital length of stay and more severe disease, the osteoclast differentiation pathway and the main target CTSK contribute to our deeper understanding for the molecular mechanisms associated with S. aureus infection-induced OM, and the construction of molecular subgroups suggested the necessity for different subgroups of patients to receive individualized treatment.
Dietary diosgenin transcriptionally down-regulated intestinal NPC1L1 expression to prevent cholesterol gallstone formation in mice
Authors: Shen Weiyi , Shao Wentao , Wang Qihan , Wang Bo , Zhao Gang , Gu Aihua , Jiang Zhaoyan , Hu Hai
Published: June 2023

Background

Cholesterol gallstone disease is a common disease. Reducing cholesterol burden is important to prevent/treat gallstone. In this study, we investigated the application of diosgenin (DG) to prevent the formation of gallstone in mice.

Methods

Adult male C57BL/6J mice were fed with the lithogenic diet (LD) only or LD supplemented with DG or ezetimibe for 8 weeks. Incidences of gallstone formation were documented. Intestine and liver tissues were collected to measure the lipid contents and expression of genes in cholesterol metabolism. Caco2 cells were treated with DG to monitor the regulation on cholesterol absorption and the transcriptional regulation of Npc1l1 gene. Changes of gut microbiota by DG was analyzed. Intraperitoneal injection of LPS on mice was performed to verify its effects on STAT3 activation and Npc1l1 expression in the small intestine.

Results

LD led to 100% formation of gallstones in mice. In comparison, dietary DG or ezetimibe supplementary completely prevents gallstones formation. DG inhibited intestinal cholesterol absorption in mice as well as in Caco2 cells by down-regulation of Npc1l1 expression. DG could directly inhibit phosphorylation of STAT3 and its transcriptional regulation of Npc1l1 expression. Furthermore, DG could modulate gut microbiota profiles and LPS mediated STAT3 activation and Npc1l1 expression.

Conclusion

Our results demonstrated that dietary DG could inhibit intestinal cholesterol absorption through decreasing NPC1L1 expression to prevent cholesterol gallstone formation.
WEE1 and PARP-1 play critical roles in myelodysplastic syndrome and acute myeloid leukemia treatment
Authors: Okabe Seiichi , Tanaka Yuko , Moriyama Mitsuru , Gotoh Akihiko
Published: June 2023

Background

Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder defined by cytopenia and is associated with an increased risk of transformation to acute myeloid leukemia (AML). The outcome of MDS is poor, so alternative therapeutic approaches are needed to improve survival. The inhibition of the DNA damage response pathway, including poly (ADP-ribose) polymerase-1 (PARP-1), has been approved to treat several cancers. In addition, WEE1, a nuclear kinase, is overexpressed in many cancers. Therefore, a WEE1 inhibitor combined with a PARP-1 inhibitor could inhibit the proliferation of MDS and AML.

Methods

We analyzed whether WEE1 was regulated in the progression of MDS and AML. We also evaluated the efficacy of MK-1775 (WEE1 inhibitor) and talazoparib (PARP-1 inhibitor).

Results

PARP-1 expression was higher in the AML cells than in the MDS cells. However, WEE1 expression remained unchanged. MK-1775 or talazoparib alone inhibited MDS and AML cells after 72 h, and cellular cytotoxicity and caspase 3/7 activity were increased. The combined use of MK-1775 and talazoparib produced superior efficacy than either drug alone and SKM-1 colony formation was reduced. Significant cell populations in the sub-G1 phase were found in the cell-cycle analyses. Additionally, γ-H2AX expression and caspase 3 activity were increased. The combined treatment also changed the mitochondrial membrane potential.

Conclusions

The combination of a WEE1 inhibitor and PARP-1 inhibitor had enhanced efficacy and is proposed as a new therapeutic option for patients with MDS or AML. Our findings have clinical implications for a potential novel therapeutic strategy for MDS and AML patients.
Wildfire smoke exposure and early childhood respiratory health: a study of prescription claims data
Authors: Dhingra Radhika , Keeler Corinna , Staley Brooke S. , Jardel Hanna V. , Ward-Caviness Cavin , Rebuli Meghan E. , Xi Yuzhi , Rappazzo Kristen , Hernandez Michelle , Chelminski Ann N. , Jaspers Ilona , Rappold Ana G.
Published: June 2023

Wildfire smoke is associated with short-term respiratory outcomes including asthma exacerbation in children. As investigations into developmental wildfire smoke exposure on children’s longer-term respiratory health are sparse, we investigated associations between developmental wildfire smoke exposure and first use of respiratory medications. Prescription claims from IBM MarketScan Commercial Claims and Encounters database were linked with wildfire smoke plume data from NASA satellites based on Metropolitan Statistical Area (MSA). A retrospective cohort of live infants (2010–2016) born into MSAs in six western states (U.S.A.), having prescription insurance, and whose birthdate was estimable from claims data was constructed (N = 184,703); of these, gestational age was estimated for 113,154 infants. The residential MSA, gestational age, and birthdate were used to estimate average weekly smoke exposure days (smoke-day) for each developmental period: three trimesters, and two sequential 12-week periods post-birth. Medications treating respiratory tract inflammation were classified using active ingredient and mode of administration into three categories:: 'upper respiratory', 'lower respiratory', 'systemic anti-inflammatory'. To evaluate associations between wildfire smoke exposure and medication usage, Cox models associating smoke-days with first observed prescription of each medication category were adjusted for infant sex, birth-season, and birthyear with a random intercept for MSA. Smoke exposure during postnatal periods was associated with earlier first use of upper respiratory medications (1–12 weeks: hazard ratio (HR) = 1.094 per 1-day increase in average weekly smoke-day, 95%CI: (1.005,1.191); 13–24 weeks: HR = 1.108, 95%CI: (1.016,1.209)). Protective associations were observed during gestational windows for both lower respiratory and systemic anti-inflammatory medications; it is possible that these associations may be a consequence of live-birth bias. These findings suggest wildfire smoke exposure during early postnatal developmental periods impact subsequent early life respiratory health.
Universal chromatin state annotation of the mouse genome
Authors: Vu Ha , Ernst Jason
Published: June 2023

A large-scale application of the “stacked modeling” approach for chromatin state discovery previously provides a single “universal” chromatin state annotation of the human genome based jointly on data from many cell and tissue types. Here, we produce an analogous chromatin state annotation for mouse based on 901 datasets assaying 14 chromatin marks in 26 cell or tissue types. To characterize each chromatin state, we relate the states to external annotations and compare them to analogously defined human states. We expect the universal chromatin state annotation for mouse to be a useful resource for studying this key model organism’s genome.
“In the back of my mind”: A Longitudinal Multiple Case Study Analysis of Successful Black Women Biomedical Graduate Students Navigating Gendered Racism
Authors: Womack Veronica Y. , Onyango Letitia , Campbell Patricia B. , McGee Richard
Published: June 2023

The coping strategies for dealing with negative racial stereotypes, among the Black women in this longitudinal case study analysis, shifted from opting to ‘prove others wrong’ or working harder to leaning on their social networks for camaraderie and advice.
Moving beyond ontological (worldview) supremacy: Indigenous insights and a recovery guide for settler-colonial scientists
Authors: Hird Coen , David-Chavez Dominique M. , Gion Shanny Spang , van Uitregt Vincent
Published: June 2023

Greater engagement and representation of Indigenous voices, knowledges and worldviews in the biological sciences is growing globally through efforts to bring more Indigenous academics into scientific research and teaching institutions. Although the intentions of such efforts may be admirable, these spaces often become sites of great personal tension for the Indigenous scholars who must ‘bridge’ or ‘facilitate’ a dialogue between Indigenous and settler-colonial (predominantly Western) knowledge traditions and worldviews. We are a small collective of early career Indigenous scholars from Australia, the United States and Aotearoa New Zealand, and we have gained insights into this situation through the unique experiential learning afforded by navigating such tensions. Here, we discuss tensions that bear remarkable similarities across geographies, cultures and settler-colonial contexts. In doing so, we aim to support other Indigenous scientists and scholars navigating settler-colonial and Western research institutions, while offering guidance, suggestions and reflections for the scientific community to allow the development of more nuanced strategies to support Indigenous academics than simply increasing Indigenous representation. We imagine transformed, innovative research and teaching agendas where Indigenous knowledges can thrive, and Indigenous scientists can apply themselves with mutual and balanced respect and reciprocity.
Επαγγελματικές ανησυχίες πτυχιούχων προσαρμοσμένης φυσικής δραστηριότητας
Authors: Καρκαλέτση Φεβρωνία
Published: June 2023

Οι επαγγελματικές ανησυχίες των πτυχιούχων Σχολών Επιστήμης της Φυσικής Αγωγής και Αθλητισμού (εφεξής ΣΕΦΑΑ) σχετίζονται τόσο με πρακτικά ζητήματα, που αφορούν στην ίδια την εργασία, όσο και με θέματα σταδιοδρομίας και εξέλιξης. Στη σύγχρονη αγορά εργασίας αναδεικνύονται πτυχές, οι οποίες σχετίζονται είτε με προβλήματα και φόβους, είτε με ευκαιρίες για αναβάθμιση δεξιοτήτων και αναπροσαρμογή εργασιακών στόχων. Με γνώμονα τις ραγδαίες εξελίξεις, η παρούσα μελέτη σχεδιάστηκε για να: α) αποτυπώσει τις επαγγελματικές ανησυχίες, β) αξιολογήσει την επαγγελματική προσαρμοστικότητα και γ) ανιχνεύσει τον φόβο για την Coronavirus Disease 2019 (εφεξής Covid-19) και τη σχέση της με την επαγγελματική προσαρμοστικότητα, σε πτυχιούχους ΣΕΦΑΑ με ειδίκευση στην Προσαρμοσμένη Φυσική Δραστηριότητα (εφεξής ΠΦΔ).Για την καλύτερη κατανόηση του θέματος χρησιμοποιήθηκε μεικτή μέθοδος συλλογής δεδομένων. Η συλλογή των ποσοτικών δεδομένων προήλθε από την χορήγηση των κλιμάκων Επαγγελματικής Προσαρμοστικότητας και Μέτρησης του Φόβου για την Covid-19 σε 174 πτυχιούχους της ΣΕΦΑΑ, ενώ τα ποιοτικά δεδομένα παράχθηκαν από ημιδομημένες συνεντεύξεις, σε έξι πτυχιούχους ΣΕΦΑΑ, με ειδίκευση στην ΠΦΔ. Τα ποσοτικά αποτελέσματα αξιολογήθηκαν στατιστικά με το Statistical Package for the Social Sciences (εφεξής SPSS), με έλεγχο Cronbach alpha, πολυμεταβλητικές και μονομεταβλητικές αναλύσεις διασποράς / Multivariate Analysis of the Variance (εφεξής MANOVA) & Analysis of the Variance (εφεξής ANOVA). Για την ποιοτική ανάλυση των δεδομένων, επιλέχθηκε ανάλυση περιεχομένου και ένα οργανωμένο σύστημα κατηγοριών, που προέκυψε από τις συνεντεύξεις.Αναφορικά με τα ποσοτικά αποτελέσματα, ο έλεγχος εσωτερικής συνοχής των ερωτημάτων στην CAAS έδωσε ικανοποιητικούς δείκτες αξιοπιστίας (α= .817 έως .855). Για τον έλεγχο δομικής εγκυρότητας χρησιμοποιήθηκε διερευνητική ανάλυση παραγόντων και τα αποτελέσματα συμφώνησαν με τη διεθνή βιβλιογραφία, πιστοποιώντας τους τέσσερις παράγοντες της CAAS (ανησυχία, έλεγχος, περιέργεια, αυτοπεποίθηση). Η πολυμεταβλητική ανάλυση διασποράς, αναφορικά με τα δημογραφικά στοιχεία, δεν έδειξε διαφοροποίηση στην επαγγελματική προσαρμοστικότητα, με εξαίρεση την ολοκλήρωση μεταπτυχιακών/διδακτορικών σπουδών. H κλίμακα Fear of COVID-19 Scale (εφεξής FVC-19S) δεν παρουσίασε κάποια στατιστικά σημαντική συσχέτιση με κάποια από τις δημογραφικές μεταβλητές, που αξιολογήθηκαν και με κανέναν από τους τέσσερις παράγοντες της CAAS. Όσον αφορά στα ποιοτικά δεδομένα, η ανάλυση περιεχομένου ανέδειξε 5 κατηγορίες, με συνολικά 24 καταχωρήσεις. Τα ποιοτικά δεδομένα αποκάλυψαν εκφάνσεις των επαγγελματικών ανησυχιών, οι οποίες σχετίζονταν με περιβαλλοντικούς και ενδο-ατομικούς παράγοντες, τόσο πριν όσο και κατά τη διάρκεια της πανδημίας. Επιπλέον, εντοπίστηκαν τομείς της αγοράς εργασίας, οι οποίοι υπολείπονταν κατά τη διάρκεια των σπουδών και θεωρούνται απαραίτητοι για την κατάλληλη προετοιμασία και την καλύτερη εργασιακή ένταξη.
Working Paper 44: Perceptions of corruption and anti-corruption efforts in Bulgaria
Authors: Bailer Stefanie , Thürk Maria
Published: June 2023

The Working Paper presents the results of a nationwide survey of 1,209 individuals in Bulgaria, conducted in February to early March 2023.

The survey examined how corruption is perceived in Bulgaria by different types of respondent, and what kind of behaviour is considered acceptable.

It also looked at respondents’ perceptions of anti-corruption efforts and under which circumstances they would be more likely to report corruption to the authorities.
Characteristics of diagnostic defects in traumatic brain injury (forensic medical approach)
Authors: Pletenetska A.
Published: June 2023

Diagnostic defects in the evaluation of TBI, such as the violation of protocols, neglect of neurological symptoms, and incorrect description of head injuries, can significantly impact the diagnosis and forensic assessment of TBI. The study of defects in the provision of medical care in traumatic brain injury (TBI) was conducted based on the data from forensic medical examinations of Kharkiv Regional Bureau of Forensic Medical Examination (KhRBFME) (307) and SI "Main Bureau of Forensic Medical Examination of the Ministry of Health of Ukraine" (SI MBFME) (226). The largest number of undiagnosed diagnostic and treatment measures related to clinically mild forms of TBI due to incomplete description of the neurological status, failure to consider the complete neurological symptomatology specific to a particular form of TBI, diagnosis based solely on subjective complaints of the patient and historical data (head injury, according to the patient's words), lack of patient examination by related specialists, and absence of additional investigations. Significant defects influencing the forensic medical assessment of TBI in the affected individuals included: incomplete description of neurological symptomatology (91±2.4%), absence of trauma history (23.5±1.8%), defects in describing external head injuries (67.9±2.0%), simulation, and aggravation.
Commotio cordis – a review of a rare cause of sudden death in young athletes
Authors: Pawęska Wojciech , Dominik Hanna , Radwański Jan , Czudy Zuzanna , Polatowska Marika , Gadomska Anna , Kurek Justyna , Gorzyński Rafał , Garstka Michał , Molczyk-Sieńczak Justyna
Published: June 2023

Commotio cordis, from Latin “agitation of the heart” is a potentially fatal sudden disruption and alteration of heart electric activity. It is usually caused by relatively mild blunt non-penetrating trauma to the specific point on anterior part of the chest wall during beginning of the heart muscle repolarization phase. It leads to ventricular fibrillation presenting as a collapse few seconds after the blow. It can be lethal without taking proper steps of management in a short ammount of time.
Influence of selected food in the profilactice and treatment of osteoporosis
Authors: Gorzyński Rafał , Kurek Justyna , Gadomska Anna , Molczyk-Sieńczak Justyna , Garstka Michał , Dominik Hanna , Czudy Zuzanna , Pawęska Wojciech , Polatowska Marika , Radwański Jan
Published: June 2023

Introduction:
The proper diet plays an extremely important role in the development of the skeletal
system from an early age This is one of the few modifiable factors that we can influence by
choosing the right food. In the case of osteoporosis, nutrition is not only important during
the period of growth, but also for the rest of life, which allows to reduce pathological
changes in bones and counteract the effects of reduced bone mineral density such as
fractures or death.
Purpose of the work:
The aim of the study was to answer the question of which nutrients have a significant
impact on bone tissue metabolism and minimize the risk of osteoporosis and its
consequences, as well as what substances contained in food may be used in the future by
medicine for preventive purposes.
Summary:
Without a doubt, the provision of adequate recommended doses of nutrients with food is crucial for the prevention and treatment of osteoporosis and its consequences, but it should
be remembered that the recommended doses are averaged. As studies show, the absorption
of the described substances can vary depending on the food contained in the diet, as well as
the age of a person, so the recommended doses of patients should be obtained individually,
taking into account dietary preferences and laboratory results. In addition, compounds such as isoflavones, while promising in the prevention of this condition, should not be routinely used as a replacement for estrogen hormone therapy, due to the still small amount of research and their ambiguous results. It is worth remembering that often the diet turns out to be an insufficient preventive measure and should be combined with pharmacotherapy.
Materials and methods:
Literature review in the database PubMed, Google Scholar, Springer Link, MDPI,
using the keywords: Osteoporosis, diet, calcium, phosphorus, vitamin D, Vitamin K,
magnesium, isoflavone.