bluuebunny/crossref_metadata_2025 huggingface dataset:
Teachers, Learners and Programs in String Education: A Review of Research
Authors: Hamann Keitha Lucas
Published: March 2023

Developing an effective string education system is the goal of educators and researchers alike. In order to do this educators need to be made aware of how students learn, what student attitudes affect learning and retention, and how effective programs address the many issues facing string educators. The purposes of this paper are to describe research related to the aptitude, attitude and achievement of individuals in string teaching/learning situations, to present research that describes interference to string learning such as injury, and to describe effective string programs both past and present. The paper is divided into three sections. The first section presents research related to string teaching while the second section focuses on string learners from preschool through adult. The third section describes both current and historical string programs.
Factors Affecting Bowed String-Instrument Selection: Evaluating Differences by Gender and Performance Experience
Authors: Nolan Karin K.
Published: March 2023

The researcher evaluated various factors contributing to string-orchestra instrument selection. Guiding questions included: (1) What are the most important factors used by beginners today when choosing to play a particular instrument? (2) Are these factors similar to or different from factors used by players who initially chose their instruments ten or more years ago? (3) Does gender play a significant role in self-reported reasons for string-instrument selection? A survey—administered to randomized beginning string orchestra students (n = 174) and professional string orchestra players (n = 155)—evaluated the significance of the following seven factors related to instrument choice: instrument sound, look, size, family influence, peer influence, music teacher influence, and economic resources. Both groups rated instrument sound as the most influential factor relating to their instrument choices, followed by parental influence. The other five selection factors were rated significantly higher by the beginners. No significant difference was found by gender.
Staffing Schools to Support the Classroom: Examining Student-to-School-Counselor Ratios and Academic Student Outcomes in Texas
Authors: Brown Carleton H. , Knight David
Published: March 2023

Although previous studies have examined the influence of school counselor ratios on student outcomes for various states, no prior studies of counselor ratios focused on schools in Texas. Utilizing data from the National Center for Education Statistics, the Stanford Education Data Archive, the U.S. Census Bureau, and the Texas Education Agency, we found that lower ratios were significantly associated with student achievement and dropout and graduation rates in Texas.
Seroprevalence of Hepatitis B Virus Infection and Associated Factors Among Pregnant Women Attending Antenatal Care At Public Hospitals in Borena Zone, Southern Ethiopia
Authors: Kampe Abdo , Kannaiyan Abbai Moorthy , Tilahun Dagnamyelew , Daka Deresse , Aliyo Alqeer , Dedecha Wako , Edin Alo
Published: March 2023

Background

Hepatitis B virus (HBV) is one of the major threats to global health, affecting millions of people each year and causing morbidity and mortality. The risk of acquiring chronic HVV infection varies with age, with 90% of infections acquired during the perinatal period. Despite many studies, there is little evidence of this virus in the Borena Zone.

Objectives

This study was done to assess seroprevalence HBVinfection and associated factors among pregnant women attending antenatal care at selected Borena Zone public hospitals from June 1 to September 30, 2022.

Methods

A cross-institutional study was conducted on 368 randomly selected pregnant women who received antenatal care at Yabelo General Hospital and Moyale Primary Hospital. Data on sociodemographic and HBV-related factors were collected using a structured questionnaire. A 5 mL blood sample is then taken and tested using a diagnostic method, the enzyme-linked immunosorbent assay. Finally, data were entered using Epidata version 3.1 and exported to SPSS version 25 and Stata version 14 for analysis. Independent predictors were identified using logistic regression analysis and P < .05 was considered statistically significant.

Results

The prevalence of HBV infection was 21 (5.7%) (95% confidence interval [CI], 3.74-8.61). History of hospitalization (adjusted odds ratio [AOR] =  3.44, 95% CI, 1.07-11.09), traditional tonsillectomy (AOR =  4.16, 95% CI, 1.29-13.40), history of sexually transmitted infection (AOR = 5.99, 95% CI, 1.81-19.85), human immunodeficiency virus (HIV) (AOR = 8.28, 95% CI, 1.66-41.41), and alcohol drinking (AOR = 5.08, 95% CI, 1.49-17.31) were independent predictors of HBV infection.

Conclusions

The results of this study indicate a moderate prevalence of HBV in selected public hospitals in the Borena Zone. History of hospitalization, traditional tonsillectomy, sexually transmitted infections, HIV, and alcohol use was significantly associated with HBV infection. Therefore, there is a need to conduct health education and more community-based research on disease transmission routes.
Application of Frailty Quantile Regression Model to Investigate of Factors Survival Time in Breast Cancer: A Multi-Center Study
Authors: Yazdani Akram , Zeraati Hojjat , Haghighat Shahpar , Kaviani Ahmad , Yaseri Mehdi
Published: March 2023

Background

The prognostic factors of survival can be accurately identified using data from different health centers, but the structure of multi-center data is heterogeneous due to the treatment of patients in different centers or similar reasons. In survival analysis, the shared frailty model is a common way to analyze multi-center data that assumes all covariates have homogenous effects. We used a censored quantile regression model for clustered survival data to study the impact of prognostic factors on survival time.

Methods

This multi-center historical cohort study included 1785 participants with breast cancer from four different medical centers. A censored quantile regression model with a gamma distribution for the frailty term was used, and p-value less than 0.05 considered significant.

Results

The 10th and 50th percentiles (95% confidence interval) of survival time were 26.22 (23–28.77) and 235.07 (130–236.55) months, respectively. The effect of metastasis on the 10th and 50th percentiles of survival time was 20.67 and 69.73 months, respectively (all p-value < 0.05). In the examination of the tumor grade, the effect of grades 2 and 3 tumors compare with the grade 1 tumor on the 50th percentile of survival time were 22.84 and 35.89 months, respectively (all p-value < 0.05). The frailty variance was significant, which confirmed that, there was significant variability between the centers.

Conclusions

This study confirmed the usefulness of a censored quantile regression model for cluster data in studying the impact of prognostic factors on survival time and the control effect of heterogeneity due to the treatment of patients in different centers.
Perceptions of Nurses Delivering Nursing Home Virtual Care Support: A Qualitative Pilot Study
Authors: Mills Carol A. , Tran Yvette , Yeager Valerie A. , Unroe Kathleen T. , Holmes Ann , Blackburn Justin
Published: March 2023

Avoidable hospitalizations among nursing home residents result in poorer health outcomes and excess costs. Consequently, efforts to reduce avoidable hospitalizations have been a priority over the recent decade. However, many potential interventions are time-intensive and require dedicated clinical staff, although nursing homes are chronically understaffed. The OPTIMISTIC project was one of seven programs selected by CMS as “enhanced care & coordination providers” and was implemented from 2012 to 2020. This qualitative study explores the perceptions of the nurses that piloted a virtual care support project developed to expand the program’s reach through telehealth, and specifically considered how nurses perceived the effectiveness of this program. Relationships, communication, and access to information were identified as common themes facilitating or impeding the perceived effectiveness of the implementation of virtual care support programs within nursing homes.
“Teaching Through Your Fingertips”: A Descriptive Study to Understand the Experiences and Needs of Online Educators in Postgraduate Nursing Education in Australia
Authors: Biedermann Narelle , Ahern Tracey
Published: March 2023

Introduction

Even before COVID-19, enrolments in online postgraduate nursing and midwifery courses were growing globally. Teaching into planned online courses requires pedagogical considerations unique to the context.

Objective

The objective of this descriptive mixed methods study was to understand the experiences and needs of Australian online educators who taught into planned online postgraduate nursing or midwifery courses.

Methods

A 55-item online survey captured the experiences and needs of participants. This paper reports on the analysis of participants’ qualitative responses in this survey, analyzed using a thematic analysis approach. Forty-nine postgraduate educators participated in this study.

Results

Five core themes were identified: time is precious; redefining the educator role; understanding the pedagogical shift; online and alone; and learning to teach online. Many educators report lacking the skills and confidence to deliver high-quality education to postgraduate students through their fingertips.

Conclusion

This research highlighted that online educators need support through resources, education, and professional development.
Intravenous Reelin Treatment Rescues Atrophy of Spleen White Pulp and Correlates to Rescue of Forced Swim Test Immobility and Neurochemical Alterations Induced by Chronic Stress
Authors: Reive B.S. , Johnston Jenessa N. , Sánchez-Lafuente Carla L. , Zhang Lucy , Chang Aland , Zhang Jasmine , Allen Josh , Romay-Tallon Raquel , Kalynchuk Lisa E. , Caruncho Hector J.
Published: March 2023

Reelin, an extracellular matrix protein with putative antidepressant-like properties, becomes dysregulated by chronic stress. Improvement in cognitive dysfunction and depression-like behavior induced by chronic stress has been reported with both intrahippocampal and intravenous Reelin treatment but the mechanisms responsible are not clear. To determine if treatment with Reelin modifies chronic stress-induced dysfunction in immune organs and whether this relates to behavioral and/or neurochemical outcomes, spleens were collected from both male (n = 62) and female (n = 53) rats treated with daily corticosterone injections for three weeks that received Reelin or vehicle. Reelin was intravenously administered once on the final day of chronic stress, or repeatedly, with weekly treatments throughout chronic stress. Behavior was assessed during the forced swim test and the object-in-place test. Chronic corticosterone caused significant atrophy of the spleen white pulp, but treatment with a single shot of Reelin restored white pulp in both males and females. Repeated Reelin injections also resolved atrophy in females. Correlations were observed between recovery of white pulp atrophy and recovery of behavioral deficits and expression of both Reelin and glutamate receptor 1 in the hippocampus, supporting a role of the peripheral immune system in the recovery of chronic stress-induced behaviors following treatment with Reelin. Our data adds to research indicating Reelin could be a valuable therapeutic target for chronic stress-related disorders including major depression.
Utility of targeted gene sequencing to differentiate myeloid malignancies from other cytopenic conditions
Authors: DeZern Amy E. , Goll Johannes B. , Lindsley R. Coleman , Bejar Rafael , Wilson Steffanie H. , Hebert Donnie , Deeg Joachim , Zhang Ling , Gore Steven , Al Baghdadi Tareq , Maciejewski Jaroslaw , Liu Jane , Padron Eric , Komrojki Rami , Saber Wael , Abel Gregory , Kroft Steven H. , Harrington Alexandra , Grimes Tyler , Reed Harrison , Fulton Robert S. , DiFronzo Nancy L. , Gillis Nancy , Sekeres Mikkael A. , Walter Matthew J.
Published: March 2023

The National Heart, Lung, and Blood Institute–funded National MDS Natural History Study (NCT02775383) is a prospective cohort study enrolling patients with cytopenia with suspected myelodysplastic syndromes (MDS) to evaluate factors associated with disease. Here, we sequenced 53 genes in bone marrow samples harvested from 1298 patients diagnosed with myeloid malignancy, including MDS and non-MDS myeloid malignancy or alternative marrow conditions with cytopenia based on concordance between independent histopathologic reviews (local, centralized, and tertiary to adjudicate disagreements when needed). We developed a novel 2-stage diagnostic classifier based on mutational profiles in 18 of 53 sequenced genes that were sufficient to best predict a diagnosis of myeloid malignancy and among those with a predicted myeloid malignancy, predict whether they had MDS. The classifier achieved a positive predictive value (PPV) of 0.84 and negative predictive value (NPV) of 0.8 with an area under the receiver operating characteristic curve (AUROC) of 0.85 when classifying patients as having myeloid vs no myeloid malignancy based on variant allele frequencies (VAFs) in 17 genes and a PPV of 0.71 and NPV of 0.64 with an AUROC of 0.73 when classifying patients as having MDS vs non-MDS malignancy based on VAFs in 10 genes. We next assessed how this approach could complement histopathology to improve diagnostic accuracy. For 99 of 139 (71%) patients (PPV of 0.83 and NPV of 0.65) with local and centralized histopathologic disagreement in myeloid vs no myeloid malignancy, the classifier-predicted diagnosis agreed with the tertiary pathology review (considered the internal gold standard).
Nonpharmacological management of psychological distress in people with COPD
Authors: Volpato Eleonora , Farver-Vestergaard Ingeborg , Brighton Lisa Jane , Peters Jeannette , Verkleij Marieke , Hutchinson Ann , Heijmans Monique , von Leupoldt Andreas
Published: March 2023

Psychological distress is prevalent in people with COPD and relates to a worse course of disease. It often remains unrecognised and untreated, intensifying the burden on patients, carers and healthcare systems. Nonpharmacological management strategies have been suggested as important elements to manage psychological distress in COPD. Therefore, this review presents instruments for detecting psychological distress in COPD and provides an overview of available nonpharmacological management strategies together with available scientific evidence for their presumed benefits in COPD. Several instruments are available for detecting psychological distress in COPD, including simple questions, questionnaires and clinical diagnostic interviews, but their implementation in clinical practice is limited and heterogeneous. Moreover, various nonpharmacological management options are available for COPD, ranging from specific cognitive behavioural therapy (CBT) to multi-component pulmonary rehabilitation (PR) programmes. These interventions vary substantially in their specific content, intensity and duration across studies. Similarly, available evidence regarding their efficacy varies significantly, with the strongest evidence currently for CBT or PR. Further randomised controlled trials are needed with larger, culturally diverse samples and long-term follow-ups. Moreover, effective nonpharmacological interventions should be implemented more in the clinical routine. Respective barriers for patients, caregivers, clinicians, healthcare systems and research need to be overcome.
Improvement of vaginal probiotics Lactobacillus crispatus on intrauterine adhesion in mice model and in clinical practice
Authors: Wu Fei , Kong Yao , Chen Wenjie , Liang Dingfa , Xiao Qin , Hu Lijuan , Tan Xiao , Wei Jing , Liu Yujuan , Deng Xiaorong , Liu Zhaoxia , Chen Tingtao
Published: March 2023

Background

Intrauterine adhesion (IUA) is a frequent acquired endometrial condition, for which there is no effective preventive or treatment. Previous studies have found that vaginal microbiota dysregulation is closely related to endometrial fibrosis and IUA. Therefore, we wondered whether restoration of vaginal microbiota by vaginal administration ofL. crispatuscould prevent endometrial fibrosis and ameliorate IUA.

Results

First, we created a mechanically injured mouse model of IUA and restored the mice’s vaginal microbiota by the addition ofL. crispatusconvolvulus. The observations suggested that intrauterine injections ofL. crispatussignificantly decreased the degree of uterine fibrosis, the levels of IL-1β and TNF-α in blood, and downregulated the TGF-β1/SMADs signaling pathway in IUA mice. A therapy withL. crispatusconsiderably raised the abundance of the helpful bacteriaLactobacillusandOscillospiraand restored the balance of the vaginal microbiota in IUA mice, according to high-throughput sequencing. Then we conducted a randomized controlled trial to compare the therapeutic effect ofL. crispatuswith estrogen after transcervical resection of adhesion (TCRA). And the results showed that vaginal probiotics had a better potential to prevent intrauterine adhesion than estrogen.

Conclusions

This study confirmed thatL. crispatuscould restore vaginal microbiota after intrauterine surgery, inhibit endometrial fibrosis, and finally play a preventive and therapeutic role in IUA. At the same time, it is a new exploration for the treatment of gynecological diseases with vaginal probiotics.

Clinical trial registration

:http://www.chictr.org.cn/, identifier (ChiCTR1900022522), registration time: 15/04/2019.
A novel rubber tree PR-10 protein involved in host-defense response against the white root rot fungus Rigidoporus microporus
Authors: Longsaward Rawit , Pengnoo Ashara , Kongsawadworakul Panida , Viboonjun Unchera
Published: March 2023

Background

White root rot disease in rubber trees, caused by the pathogenic fungi Rigidoporus microporus, is currently considered a major problem in rubber tree plantations worldwide. Only a few reports have mentioned the response of rubber trees occurring at the non-infection sites, which is crucial for the disease understanding and protecting the yield losses.

Results

Through a comparative proteomic study using the two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) technique, the present study reveals some distal-responsive proteins in rubber tree leaves during the plant-fungal pathogen interaction. From a total of 12 selected differentially expressed protein spots, several defense-related proteins such as molecular chaperones and ROS-detoxifying enzymes were identified. The expression of 6 candidate proteins was investigated at the transcript level by Reverse Transcription Quantitative PCR (RT-qPCR). In silico, a highly-expressed uncharacterized protein LOC110648447 found in rubber trees was predicted to be a protein in the pathogenesis-related protein 10 (PR-10) class. In silico promoter analysis and structural-related characterization of this novel PR-10 protein suggest that it plays a potential role in defending rubber trees against R. microporus infection. The promoter contains WRKY-, MYB-, and other defense-related cis-acting elements. The structural model of the novel PR-10 protein predicted by I-TASSER showed a topology of the Bet v 1 protein family, including a conserved active site and a ligand-binding hydrophobic cavity.

Conclusions

A novel protein in the PR-10 group increased sharply in rubber tree leaves during interaction with the white root rot pathogen, potentially contributing to host defense. The results of this study provide information useful for white root rot disease management of rubber trees in the future.
"SARCOPENIA MEASURED BY ULTRASOUND IN HOSPITALIZED OLDER ADULTS" (ECOSARC): multi-centre, prospective observational study protocol
Authors: López Jiménez Esther , Neira Álvarez Marta , Ramírez Martín Raquel , Alonso Bouzón Cristina , Amor Andrés María Solange , Bermejo Boixareu Cristina , Brañas Fátima , Menéndez Colino Rocío , Arias Muñana Estefanía , Checa López Marta , Grau Jiménez Concha , Pérez Rodríguez Patricia , Alcantud Ibáñez María , Vasquez Brolen Brian , Oliva Juan , Peña Longobardo Luz María , Alcantud Córcoles Rubén , Cortés Zamora Elisa Belén , Gómez Jiménez Elena , Romero Rizos Luis , Avendaño Céspedes Almudena , Hernández Socorro Carmen Rosa , Abizanda Pedro
Published: March 2023

Background

Measurement of muscle mass and function, and thereafter, screening and diagnosis of sarcopenia, is a challenge and a need in hospitalized older adults. However, it is difficult in complex real-world old patients, because usually they are unable to collaborate with clinical, functional, and imaging testing. Ultrasound measurement of quadriceps rectus femoris (QRF) provides a non-invasive, real-time assessment of muscle quantity and quality, and is highly acceptable to participants with excellent inter-rater and intra-rater variability. However, normative data, protocol standardization, and association with longitudinal outcomes, needs further research and consensus.

Methods

Prospective exploratory multicenter study in older adults admitted to Acute Geriatric Units (AGUs) for medical reasons. 157 subjects from 7 AGUs of Spain were recruited between May 2019 and January 2022. Muscle ultrasound measurements of the anterior vastus of the QRF were acquired on admission and on discharge, using a previously validated protocol, using a Chieson model ECO2 ultrasound system (Chieson Medical Technologies, Co. Ltd, Wimxu District Wuxi, Jiangsu, China). Measurements included the cross-sectional area, muscle thickness in longitudinal view, intramuscular central tendon thickness, echogenicity, and the presence or absence of edema and fasciculations. Functional, nutritional, and DXA measurements were provided. Clinical follow-up was completed at discharge, and 30 and 90 days after discharge. Variations between hospital admission and discharge ultrasound values, and the relationship with clinical variables, will be analyzed using paired t-tests, Wilcoxon tests, or Mc Nemar chi-square tests when necessary. Prevalence of sarcopenia will be calculated, as well as sensitivity and specificity of ultrasound measurements to determine sarcopenia. Kappa analysis will be used to analyze the concordance between measurements, and sensitivity analysis will be conducted for each participating center.

Discussion

The results obtained will be of great interest to the scientific geriatric community to assess the utility and validity of ultrasound measurements for the detection and follow-up of sarcopenia in hospitalized older adults, and its association with adverse outcomes.

Trial registration

NCT05113758. Registration date: November 9th 2021. Retrospectively registered.
Severe CMV pneumonitis and the resulting ARDS in a 28-year-old pregnant woman: a case report
Authors: Kalogeropoulos Sotirios , Zarogianni Evgenia , Adonakis Georgios , Kaponis Apostolos
Published: March 2023

Background

Cytomegalovirus (CMV) is a common virus. In pregnant women, CMV infection is usually mildly symptomatic or asymptomatic but can lead to fetal infection. Here we present a rare case of severe CMV pneumonitis and acute respiratory distress syndrome in a healthy immunocompetent pregnant woman.

Case presentation

A previous healthy 28-year-old woman with spontaneous conception, was admitted to the General University Hospital of Patras at 29 weeks of gestation with a day history of fever, fatigue, pharyngitis, and cough. She was diagnosed with acute CMV infection and CMV pneumonitis. During her hospitalization she developed acute distress syndrome (ARDS). The patient was intubated and underwent emergency caesarean delivery. She was admitted to the intensive care unit and received intravenous ganciclovir. She was discharged at 20th day postpartum in a good clinical condition.

Conclusions

This case highlights the infrequent yet potential complexity of CMV infection in immunocompetent patients and in pregnancy.
Complete excision of giant clavicular hydatid cyst: a case report
Authors: Wang Xin , Huang Jinyong , Su Liping , Ma Qian , Ma Chao , Xie Zengru
Published: March 2023

Background

Echinococcosis, also known as hydatid disease, is a zoonotic parasitic disease prevalent in pastoral areas, mainly involving the liver and lungs, and less frequently the bones and surrounding soft tissues. Diagnosis and treatment of bone hydatid disease is a challenge, and because of the insidious course of the disease, the lesions are often widely disseminated by the time patients seek medical attention.

Case presentation

A 29-year-old woman presented with a painless mass that was gradually increasing in size in the cervical thorax. Imaging revealed an enlarged clavicle with multiple bone cortical defects and the existence of cysts in the soft tissues surrounding the clavicle, for which complete excision of the clavicle and the attached cysts was performed. There was no recurrence of the cyst within one year after the operation, and the patient felt well and had normal shoulder joint movement.

Conclusions

Bone hydatid may appear in bones throughout the body, and cysts that leak from the bone into the surrounding soft tissues may spread at a relatively rapid rate. Prompt surgical removal of the affected bone and surrounding cysts is necessary for treatment.
UMOYA: a prospective longitudinal cohort study to evaluate novel diagnostic tools and to assess long-term impact on lung health in South African children with presumptive pulmonary TB—a study protocol
Authors: Dewandel Isabelle , van Niekerk Margaret , Ghimenton-Walters Elisabetta , Palmer Megan , Anthony Michaile G. , McKenzie Carla , Croucamp Rolanda , Alter Galit , Demers Anne-Marie , van Zyl Gert , Claassen Mathilda , Goussard Pierre , Swanepoel Ruan , Hoddinott Graeme , Bosch Corne , Dunbar Rory , Allwood Brian , McCollum Eric D. , Schaaf H. Simon , Hesseling Anneke C. , van der Zalm Marieke M.
Published: March 2023

Background

Despite a high paediatric tuberculosis (TB) burden globally, sensitive and specific diagnostic tools are lacking. In addition, no data exist on the impact of pulmonary TB on long-term child lung health in low- and middle-income countries. The prospective observational UMOYA study aims (1) to build a state-of-the-art clinical, radiological, and biological repository of well-characterised children with presumptive pulmonary TB as a platform for future studies to explore new emerging diagnostic tools and biomarkers for early diagnosis and treatment response; and (2) to investigate the short and long-term impact of pulmonary TB on lung health and quality of life in children.

Methods

We will recruit up to 600 children (0–13 years) with presumptive pulmonary TB and 100 healthy controls. Recruitment started in November 2017 and is expected to continue until May 2023. Sputum and non-sputum-based samples are collected at enrolment and during follow-up in TB cases and symptomatic controls. TB treatment is started by routine care services. Intensive follow-up for 6 months will allow for TB cases to retrospectively be classified according to international consensus clinical case definitions for TB. Long-term follow-up, including imaging, comprehensive assessment of lung function and quality of life questionnaires, are done yearly up to 4 years after recruitment.

Discussion

The UMOYA study will provide a unique platform to evaluate new emerging diagnostic tools and biomarkers for early diagnosis and treatment response and to investigate long-term outcomes of pulmonary TB and other respiratory events on lung health in children.
Antifibrotic mechanism of avitinib in bleomycin-induced pulmonary fibrosis in mice
Authors: Miao Yang , Wang Yanhua , Bi Zhun , Huang Kai , Gao Jingjing , Li Xiaohe , Li Shimeng , Wei Luqing , Zhou Honggang , Yang Cheng
Published: March 2023

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by alveolar epithelial cell injury and lung fibroblast overactivation. At present, only two drugs are approved by the FDA for the treatment of IPF, including the synthetic pyridinone drug, pirfenidone, and the tyrosine kinase inhibitor, nintedanib. Avitinib (AVB) is a novel oral and potent third-generation tyrosine kinase inhibitor for treating non-small cell lung cancer (NSCLC). However, the role of avitinib in pulmonary fibrosis has not yet been established. In the present study, we used in vivo and in vitro models to evaluate the role of avitinib in pulmonary fibrosis. In vivo experiments first verified that avitinib significantly alleviated bleomycin-induced pulmonary fibrosis in mice. Further in vitro molecular studies indicated that avitinib inhibited myofibroblast activation, migration and extracellular matrix (ECM) production in NIH-3T3 cells, mainly by inhibiting the TGF-β1/Smad3 signalling pathways. The cellular experiments also indicated that avitinib improved alveolar epithelial cell injury in A549 cells. In conclusion, the present findings demonstrated that avitinib attenuates bleomycin-induced pulmonary fibrosis in mice by inhibiting alveolar epithelial cell injury and myofibroblast activation.
Unsupervised encoding selection through ensemble pruning for biomedical classification
Authors: Spänig Sebastian , Michel Alexander , Heider Dominik
Published: March 2023

Background

Owing to the rising levels of multi-resistant pathogens, antimicrobial peptides, an alternative strategy to classic antibiotics, got more attention. A crucial part is thereby the costly identification and validation. With the ever-growing amount of annotated peptides, researchers leverage artificial intelligence to circumvent the cumbersome, wet-lab-based identification and automate the detection of promising candidates. However, the prediction of a peptide’s function is not limited to antimicrobial efficiency. To date, multiple studies successfully classified additional properties, e.g., antiviral or cell-penetrating effects. In this light, ensemble classifiers are employed aiming to further improve the prediction. Although we recently presented a workflow to significantly diminish the initial encoding choice, an entire unsupervised encoding selection, considering various machine learning models, is still lacking.

Results

We developed a workflow, automatically selecting encodings and generating classifier ensembles by employing sophisticated pruning methods. We observed that the Pareto frontier pruning is a good method to create encoding ensembles for the datasets at hand. In addition, encodings combined with the Decision Tree classifier as the base model are often superior. However, our results also demonstrate that none of the ensemble building techniques is outstanding for all datasets.

Conclusion

The workflow conducts multiple pruning methods to evaluate ensemble classifiers composed from a wide range of peptide encodings and base models. Consequently, researchers can use the workflow for unsupervised encoding selection and ensemble creation. Ultimately, the extensible workflow can be used as a plugin for the PEPTIDE REACToR, further establishing it as a versatile tool in the domain.
The WAVE3/β-catenin oncogenic signaling regulates chemoresistance in triple negative breast cancer
Authors: Wang Wei , Rana Priyanka S. , Markovic Vesna , Sossey-Alaoui Khalid
Published: March 2023

Background

Metastatic breast cancer is responsible for the death of the majority of breast cancer patients. In fact, metastatic BC is the 2nd leading cause of cancer-related deaths in women in the USA and worldwide. Triple negative breast cancer (TNBC), which lacks expression of hormone receptors (ER-α and PR) and ErbB2/HER2, is especially lethal due to its highly metastatic behavior, propensity to recur rapidly, and for its resistance to standard of care therapies, through mechanisms that remain incompletely understood. WAVE3 has been established as a promoter of TNBC development and metastatic progression. In this study, we investigated the molecular mechanisms whereby WAVE3 promotes therapy-resistance and cancer stemness in TNBC, through the regulation of β-catenin stabilization.

Methods

The Cancer Genome Atlas dataset was used to assess the expression of WAVE3 and β-catenin in breast cancer tumors. Kaplan–Meier Plotter analysis was used to correlate expression of WAVE3 and β-catenin with breast cancer patients’ survival probability. MTT assay was used to quantify cell survival. CRISPR/Cas9-mediated gene editing, 2D and 3D tumorsphere growth and invasion assays, Immunofluorescence, Western blotting, Semi-quantitative and real-time quantitative PCR analyses were applied to study the WAVE3/β-catenin oncogenic signaling in TNBC. Tumor xenograft assays were used to study the role of WAVE3 in mediating chemotherapy resistance of TNBC tumors.

Results

Genetic inactivation of WAVE3 in combination of chemotherapy resulted in inhibition of 2D growth and 3D tumorsphere formation and invasion of TNBC cells in vitro, as well as tumor growth and metastasis in vivo. In addition, while re-expression of phospho-active WAVE3 in the WAVE3-deficient TNBC cells restored the oncogenic activity of WAVE3, re-expression of phospho-mutant WAVE3 did not. Further studies revealed that dual blocking of WAVE3 expression or phosphorylation in combination with chemotherapy treatment inhibited the activity and expression and stabilization of β-catenin. Most importantly, the combination of WAVE3-deficiency or WAVE3-phospho-deficiency and chemotherapy suppressed the oncogenic behavior of chemoresistant TNBC cells, both in vitro and in vivo.

Conclusion

We identified a novel WAVE3/β-catenin oncogenic signaling axis that modulates chemoresistance of TNBC. This study suggests that a targeted therapeutic strategy against WAVE3 could be effective for the treatment of chemoresistant TNBC tumors.
The novel Nsp9-interacting host factor H2BE promotes PEDV replication by inhibiting endoplasmic reticulum stress-mediated apoptosis
Authors: Xu Xingang , Ma Mingrui , Shi Xiaojie , Yan Yuchao , Liu Yi , Yang Naling , Wang Quanqiong , Zhang Shuxia , Zhang Qi
Published: March 2023

Porcine epidemic diarrhoea (PED) caused by porcine epidemic diarrhoea virus (PEDV) has led to significant economic losses in the swine industry worldwide. Histone Cluster 2, H2BE (HIST2H2BE), the main protein component in chromatin, has been proposed to play a key role in apoptosis. However, the relationship between H2BE and PEDV remains unclear. In this study, H2BE was shown to bind and interact with PEDV nonstructural protein 9 (Nsp9) via immunoprecipitation-mass spectrometry (IP-MS). Next, we verified the interaction of Nsp9 with H2BE by immunoprecipitation and immunofluorescence. H2BE colocalized with Nsp9 in the cytoplasm and nuclei. PEDV Nsp9 upregulated the expression of H2BE by inhibiting the expression of IRX1. We demonstrated that overexpression of H2BE significantly promoted PEDV replication, whereas knockdown of H2BE by small interfering RNA (siRNA) inhibited PEDV replication. Overexpression of H2BE led to significantly inhibited GRP78 expression, phosphorylated PERK (p-PERK), phosphorylated eIF2 (p-eIF2), phosphorylated IRE1 (p-IRE1), and phosphorylated JNK (p-JNK); negatively regulated CHOP and Bax expression and caspase-9 and caspase-3 cleavage; and promoted Bcl-2 production. Knocking down H2BE exerted the opposite effects. Furthermore, we found that after deletion of amino acids 1–28, H2BE did not promote PEDV replication. In conclusion, these studies revealed the mechanism by which H2BE is associated with ER stress-mediated apoptosis to regulate PEDV replication. Nsp9 upregulates H2BE. H2BE plays a role in inhibiting apoptosis and thus facilitating viral replication, which depends on the N-terminal region of H2BE (amino acids 1–28). These findings provide a reference for host–PEDV interactions and offer the possibility for developing strategies for PEDV decontamination and prevention.
Genome-centric metagenomics reveals the host-driven dynamics and ecological role of CPR bacteria in an activated sludge system
Authors: Wang Yulin , Zhang Yulin , Hu Yu , Liu Lei , Liu Shuang-Jiang , Zhang Tong
Published: March 2023

Background

Candidate phyla radiation (CPR) constitutes highly diverse bacteria with small cell sizes and are likely obligate intracellular symbionts. Given their distribution and complex associations with bacterial hosts, genetic and biological features of CPR bacteria in low-nutrient environments have received increasing attention. However, CPR bacteria in wastewater treatment systems remain poorly understood. We utilized genome-centric metagenomics to answer how CPR communities shift over 11 years and what kind of ecological roles they act in an activated sludge system.

Results

We found that approximately 9% (135) of the 1,526 non-redundant bacterial and archaeal metagenome-assembled genomes were affiliated with CPR. CPR bacteria were consistently abundant with a relative abundance of up to 7.5% in the studied activated sludge system. The observed striking fluctuations in CPR community compositions and the limited metabolic and biosynthetic capabilities in CPR bacteria collectively revealed the nature that CPR dynamics may be directly determined by the available hosts. Similarity-based network analysis further confirmed the broad bacterial hosts of CPR lineages. The proteome contents of activated sludge-associated CPR had a higher similarity to those of environmental-associated CPR than to those of human-associated ones. Comparative genomic analysis observed significant enrichment of genes for oxygen stress resistance in activated sludge-associated CPR bacteria. Furthermore, genes for carbon cycling and horizontal gene transfer were extensively identified in activated sludge-associated CPR genomes.

Conclusions

These findings highlight the presence of specific host interactions among CPR lineages in activated sludge systems. Despite the lack of key metabolic pathways, these small, yet abundant bacteria may have significant involvements in biogeochemical cycling and bacterial evolution in activated sludge systems.
Bone health in avoidant/restrictive food intake disorder: a narrative review
Authors: Proctor Kaitlin B. , Rodrick Eugene , Belcher Staci , Sharp William G. , Kindler Joseph M.
Published: March 2023

Background

Avoidant/restrictive food intake disorder (ARFID) is an eating/feeding disturbance characterized by severe food avoidance or restriction that results in faltering growth, nutritional deficiencies, dependence on formula supplementation, and/or significant psychosocial impairment. Compared to other eating disorders, ARFID is observed to have an earlier childhood onset and chronic course without intervention. Childhood represents a sensitive period for longitudinal growth and bone accrual, setting the stage for long-term health outcomes associated with longevity and quality of life, including risk for fracture and osteoporosis.

Results

This narrative review discusses published scientific literature on bone health in individuals with ARFID by describing the current understanding of ARFID’s effect on bone health, how common dietary constraints characteristic of ARFID may present unique risks to bone health, and the current clinical recommendations for bone health assessment. Reviewing what is known of clinical data from anorexia nervosa (AN) and similar cohorts, the chronicity and etiology of dietary restriction observed in ARFID are hypothesized to compromise bone health significantly. Although limited, examination of bone health in ARFID patients suggests children with ARFID tend to have shorter stature compared to healthy reference datasets and have lower bone density compared to healthy individuals, similar to those with AN. There remains a substantial knowledge gap in how ARFID may interrupt bone accrual during childhood and adolescence, and subsequent impact on attainment of peak bone mass and peak bone strength. The longitudinal effects of ARFID may be subtle and overlooked clinically in the absence of severe weight loss or growth stunting. Early identification and remediation of threats to bone mass accrual have significant personal and population-level implications.

Conclusion

For patients with ARFID, delayed identification and intervention to address feeding disturbances may have a long-lasting impact on various body systems and processes, including those relating to longitudinal growth and bone mass accrual. Further research employing rigorous prospective observational and/or randomized study designs are required to clearly define effects of ARFID, as well as clinical interventions aimed at addressing ARFID-related feeding disturbances, on bone accrual.
School climate and academic burnout in medical students: a moderated mediation model of collective self-esteem and psychological capital
Authors: Yu Wanwan , Yao Wenjun , Chen Ming , Zhu Hongqing , Yan Jing
Published: March 2023

Background

The study burnout of medical students is more and more serious, which directly affects the study style of university and the learning quality of students. This has aroused the high attention of researchers and universities. This study aimed to explore the mechanism of the influence of school climate on academic burnout among medical students in Chinese cultural context.

Methods

2411 medical students (50.52% female; mean age = 19.55,SD = 1.41, rang = 17–24 years) were investigated with psychological environment questionnaire, collective self-esteem scale, psychological capital scale and academic burnout scale. The data were analyzed by using a moderated mediation model with SPSS and the Process 4.0 macro.

Results

The results revealed that: (1) school climate had a significant negative predictive effect on academic burnout among medical students controlling for gender, grade and age (B= -0.40,p < 0.001). (2) Collective self-esteem played a partial mediating role in school climate and academic burnout (indirect effect = -0.28, 95% CI = [-0.32,-0.25], accounting for 52.83%). (3) The first and second half of the indirect effect of school climate on medical students’ academic burnout were moderated by psychological capital (B = 0.03,p < 0.01;B= -0.09,p < 0.001).High level of psychological capital can enhance the link between school climate and collective self-esteem as well as the link between self-esteem and academic burnout.

Conclusion

Creating a good school atmosphere and improving the level of collective self-esteem and psychological capital are beneficial to improve the academic burnout of medical students.
Hereditary myopathy with early respiratory failure: case report
Authors: Petrovic Milutin , Ratinac Milos , Peric Stojan , Pusica Romana , Cekerevac Ivan
Published: March 2023

Background

Hereditary myopathy with early respiratory failure (HMERF) is a rare myopathy that affects respiratory muscles in the early course of the disease leading to respiratory insufficiency. It is caused by mutation in titin (TTN) gene.

Case report

At the age of 29, our female patient presented with a slowly progressive proximal lower limb and axial muscle weakness and respiratory issues. Her late mother had similar problems, she died at a young age and was never properly diagnosed. Patient’s creatine kinase level was elevated up to three times above the upper limit of normal. Whole exome sequencing showed a pathogenic variant c.95372G>A in the TTN gene leading to the final diagnosis of HMERF. Cardiac examination was normal. Patient started to use a non-invasive nocturnal ventilation at age of 35.

Conclusions

Our case is the first described case of HMERF in Serbian population. Multidisciplinary neurological and pulmonary approach is of great importance in HMERF and similar diseases. This case highlights the importance of considering early neuromuscular respiratory insufficiency as a distinctive syndrome leading to a challenging and broad differential diagnosis.
A review on biochemical constituents of pumpkin and their role as pharma foods; a key strategy to improve health in post COVID 19 period
Authors: Hussain Ashiq , Kausar Tusneem , Sehar Sawera , Sarwar Ayesha , Quddoos Muhammad Yousaf , Aslam Jawed , Liaqat Atif , Siddique Tahira , An Qurat Ul , Kauser Samina , Rehman Abdul , Nisar Rizwan
Published: March 2023

Progression of today’s world has been given setback due to the adversity of a novel, viral, deadly outbreak COVID 19, which raised the concerns of the scientists, researchers and health related officials about the inherent and adaptive immune system of the living body and its relation with healthy diet balanced with pharma foods. Now world is coming out of the destructive pandemic era, the choice of right food can help to build and boost adaptive immunity and pumpkin due to excellent profile of functional and nutraceutical constituents could be the part of both infected and non-infected person’s daily diet. Vitamins like A, C and E, minerals like zinc, iron and selenium, essential oils, peptides, carotenoids and polysaccharides present in pumpkin could accommodate the prevailing deficiencies in the body to fought against the viral pathogens. In current post COVID 19 scenario adequate supply of healthy diet, balanced with pharma foods could play a basic role in boosting immune system of the populations. This review covers the pharmacological activities of pumpkin functional constituents in relation with COVID 19 pandemic. Pumpkins are well equipped with nutraceuticals and functional bioactives like tocopherols, polyphenols, terpenoids and lutein therefore, consumption and processing of this remarkable vegetable could be encouraged as pharma food due to its antihyperlipidemic, antiviral, anti-inflammatory, antihyperglycemic, immunomodulatory, antihypertensive, antimicrobial and antioxidant potential. Need of healthy eating in current post COVID 19 period is very crucial for healthy population, and medicinal foods like pumpkin could play a vital role in developing a healthy community around the globe.

Graphical Abstract
Early GH Treatment Is Effective and Well Tolerated in Children With Turner Syndrome: NordiNet® IOS and Answer Program
Authors: Backeljauw Philippe , Blair Joanne C , Ferran Jean-Marc , Kelepouris Nicky , Miller Bradley S , Pietropoli Alberto , Polak Michel , Sävendahl Lars , Verlinde Franciska , Rohrer Tilman R
Published: March 2023

Context

Despite having normal growth hormone (GH) secretion, individuals with Turner syndrome (TS) have short stature. Treatment with recombinant human GH is recommended for TS girls with short stature.

Objective

This work aimed to evaluate the effectiveness and safety of Norditropin (somatropin, Novo Nordisk) with up to 10 years of follow-up in children with TS.

Methods

Secondary analysis was conducted of Norditropin data from 2 non-interventional studies: NordiNet® IOS (NCT00960128) and the ANSWER program (NCT01009905).

Results

A total of 2377 girls with TS were included in the safety analysis set (SAS), with 1513 in the treatment-naive effectiveness analysis set (EAS). At the start of treatment, 1273 (84%) participants were prepubertal (EAS); mean (SD) age was 8.8 (3.9) years. Mean (SD) dose received at the start of GH treatment was 0.045 (0.011) mg/kg/day (EAS). Mean (SD) baseline insulin-like growth factor-1 (IGF-I) SD score (SDS) was −0.86 (1.52), and mean (SD) duration of GH treatment (SAS) was 3.8 (2.8) years.

Height SDS (HSDS) increased throughout follow-up, with near-adult HSDS reached by 264 (17%) participants (mean [SD] −1.99 [0.94]; change from baseline +0.90 [0.85]). During the study, 695 (46%) participants (EAS) entered puberty at a mean (SD) age of 12.7 (1.9) years (whether puberty was spontaneous or induced was unknown). Within the SAS, mean IGF-I SDS (SD) at year 10 was 0.91 (1.69); change from baseline +1.48 (1.70). Serious adverse reactions were reported in 10 participants (epiphysiolysis [n = 3]).

Conclusion

GH-treated participants with TS responded well, without new safety concerns. Our real-world data are in agreement with previous studies.