bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractIdiopathic 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

Abstract
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

Abstract
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

AbstractPorcine 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

AbstractBackgroundCandidate 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.ResultsWe 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.ConclusionsThese 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

Abstract
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

AbstractBackgroundThe 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.Methods2411 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.ResultsThe 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.ConclusionCreating 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

Abstract
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

AbstractProgression 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

AbstractContextDespite 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.ObjectiveThis 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.MethodsSecondary analysis was conducted of Norditropin data from 2 non-interventional studies: NordiNet® IOS (NCT00960128) and the ANSWER program (NCT01009905).ResultsA 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]).ConclusionGH-treated participants with TS responded well, without new safety concerns. Our real-world data are in agreement with previous studies.