bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncogenic circ-SLC16A1 promotes progression of non-small cell lung cancer via regulation of the miR-1287-5p/profilin 2 axis
Authors: Jin Mingming , Yuan Tailei , Tian Kaisai , Li Jingjing , Huang Qingqing , Chi Yongbin , Huang Gang 
Published: March 2024

Abstract
Background
Circular RNAs (circRNAs) are single-stranded RNAs with covalently closed structures that have been implicated in cancer progression. However, the regulatory mechanisms remain largely unclear. So, the aim of this study was to reveal the role and regulatory mechanisms of circ-SLC16A1.

Methods
In this study, next-generation sequencing was used to identify abnormally expressed circRNAs between cancerous and para-carcinoma tissues. Fluorescence in situ hybridization and quantitative reverse transcription polymerase chain reaction were performed to assess the expression patterns of circ-solute carrier family 16 member 1 (SLC16A1) in non-small cell lung cancer (NSCLC) cells and tissue specimens. The dual-luciferase reporter assay was utilized to identify downstream targets of circ-SLC16A1. Transwell migration, wound healing, 5-ethynyl-2′-deoxyuridine incorporation, cell counting, and colony formation assays were conducted to assess the proliferation and migration of NSCLC cells. A mouse tumor xenograft model was employed to determine the roles of circ-SLC16A1 in NSCLC progression and metastasis in vivo.

Results
The results found that circ-SLC16A1 was upregulated in NSCLC cells and tissues. Downregulation of circ-SLC16A1 inhibited tumor growth by reducing proliferation, lung metastasis, and lymphatic metastasis of NSCLC cells, and arrested the cell cycle in the G1 phase. Also, silencing of circ-SLC16A1 promoted apoptosis of NSCLC cells. The results of bioinformatics analysis and the dual-luciferase reporter assay confirmed that microRNA (miR)-1287-5p and profilin 2 (PFN2) are downstream targets of circ-SLC16A1. PFN2 overexpression or circ-SLC16A1 inhibition restored proliferation and migration of NSCLC cells after silencing of circ-SLC16A1. PFN2 overexpression restored migration and proliferation of NSCLC cells post miR-1287-5p overexpression.

Conclusions
Collectively, these findings show that miR-1287-5p/PFN2 signaling was associated with downregulation of circ-SLC16A1 and reduced invasion and proliferation of NSCLC cells. So, circ-SLC16A1 is identified as a mediator of multiple pro-oncogenic signaling pathways in NSCLC and can be targeted to suppress tumor progression.
Genetic determinants of global developmental delay and intellectual disability in Ukrainian children
Authors: Shchubelka Khrystyna , Turova Liudmyla , Wolfsberger Walter , Kalanquin Kelly , Williston Krista , Kurutsa Oleksii , Makovetska Anastasiia , Hasynets Yaroslava , Mirutenko Violeta , Vakerych Mykhailo , Oleksyk Taras K 
Published: March 2024

Abstract
Background
Global developmental delay or intellectual disability usually accompanies various genetic disorders as a part of the syndrome, which may include seizures, autism spectrum disorder and multiple congenital abnormalities. Next-generation sequencing (NGS) techniques have improved the identification of pathogenic variants and genes related to developmental delay. This study aimed to evaluate the yield of whole exome sequencing (WES) and neurodevelopmental disorder gene panel sequencing in a pediatric cohort from Ukraine. Additionally, the study computationally predicted the effect of variants of uncertain significance (VUS) based on recently published genetic data from the country’s healthy population.

Methods
The study retrospectively analyzed WES or gene panel sequencing findings of 417 children with global developmental delay, intellectual disability, and/or other symptoms. Variants of uncertain significance were annotated using CADD-Phred and SIFT prediction scores, and their frequency in the healthy population of Ukraine was estimated.

Results
A definitive molecular diagnosis was established in 66 (15.8%) of the individuals. WES diagnosed 22 out of 37 cases (59.4%), while the neurodevelopmental gene panel identified 44 definitive diagnoses among the 380 tested patients (12.1%). Non-diagnostic findings (VUS and carrier) were reported in 350 (83.2%) individuals. The most frequently diagnosed conditions were developmental and epileptic encephalopathies associated with severe epilepsy and GDD/ID (associated genes ARX, CDKL5, STXBP1, KCNQ2, SCN2A, KCNT1, KCNA2). Additionally, we annotated 221 VUS classified as potentially damaging, AD or X-linked, potentially increasing the diagnostic yield by 30%, but 18 of these variants were present in the healthy population of Ukraine.

Conclusions
This is the first comprehensive study on genetic causes of GDD/ID conducted in Ukraine. This study provides the first comprehensive investigation of the genetic causes of GDD/ID in Ukraine. It presents a substantial dataset of diagnosed genetic conditions associated with GDD/ID. The results support the utilization of NGS gene panels and WES as first-line diagnostic tools for GDD/ID cases, particularly in resource-limited settings. A comprehensive approach to resolving VUS, including computational effect prediction, population frequency analysis, and phenotype assessment, can aid in further reclassification of deleterious VUS and guide further testing in families.
Utilizing genomic signatures to gain insights into the dynamics of SARS-CoV-2 through Machine and Deep Learning techniques
Authors: Elsherbini Ahmed M. A. , Elkholy Amr Hassan , Fadel Youssef M. , Goussarov Gleb , Elshal Ahmed Mohamed , El-Hadidi Mohamed , Mysara Mohamed 
Published: March 2024

AbstractThe global spread of the SARS-CoV-2 pandemic, originating in Wuhan, China, has had profound consequences on both health and the economy. Traditional alignment-based phylogenetic tree methods for tracking epidemic dynamics demand substantial computational power due to the growing number of sequenced strains. Consequently, there is a pressing need for an alignment-free approach to characterize these strains and monitor the dynamics of various variants. In this work, we introduce a swift and straightforward tool named GenoSig, implemented in C++. The tool exploits the Di and Tri nucleotide frequency signatures to delineate the taxonomic lineages of SARS-CoV-2 by employing diverse machine learning (ML) and deep learning (DL) models. Our approach achieved a tenfold cross-validation accuracy of 87.88% (± 0.013) for DL and 86.37% (± 0.0009) for Random Forest (RF) model, surpassing the performance of other ML models. Validation using an additional unexposed dataset yielded comparable results. Despite variations in architectures between DL and RF, it was observed that later clades, specifically GRA, GRY, and GK, exhibited superior performance compared to earlier clades G and GH. As for the continental origin of the virus, both DL and RF models exhibited lower performance than in predicting clades. However, both models demonstrated relatively higher accuracy for Europe, North America, and South America compared to other continents, with DL outperforming RF. Both models consistently demonstrated a preference for cytosine and guanine over adenine and thymine in both clade and continental analyses, in both Di and Tri nucleotide frequencies signatures. Our findings suggest that GenoSig provides a straightforward approach to address taxonomic, epidemiological, and biological inquiries, utilizing a reductive method applicable not only to SARS-CoV-2 but also to similar research questions in an alignment-free context.
The effects of individual music therapy in nursing home residents with dementia to improve general well-being: study protocol of a randomized controlled trial
Authors: Baroni Caramel Vanusa M. , van der Steen Jenny T. , Vink Annemieke C. , Janus Sarah I. M. , Twisk Jos W. R. , Scherder Erik J. A. , Zuidema Sytse U. 
Published: March 2024

Abstract
Background
Dementia is often associated with Neuropsychiatric Symptoms (NPS) such as agitation, depression, hallucinations, anxiety, that can cause distress for the resident with dementia in long-term care settings and can impose emotional burden on the environment. NPS are often treated with psychotropic drugs, which, however, frequently cause side effects. Alternatively, non-pharmacological interventions can improve well-being and maintain an optimal quality of life (QoL) of those living with dementia. Other QoL related outcomes, such as pain, discomfort and sleep disruption are relevant outcomes in music trials as well. Music therapy is a non-pharmacological intervention that can reduce NPS and improve well-being, and its associated symptoms in dementia.

Methods
The research will be conducted at eight nursing home facilities of a health care organization in the Netherlands. A sample size of 30 in each group (experimental and control group) is required, totalling 60 residents increased to 80 when considering expected drop out to follow up. The participants in the intervention group receive 30 min of individual music therapy (MT) in their own room by a music therapist twice a week for 12 weeks. The participants in the control group will receive 30 min of individual attention in their own room by a volunteer twice a week for 12 weeks. Assessments will be done at baseline, 6 weeks and 12 weeks. An independent observer, blinded for the intervention or control condition, will assess directly observed well-being (primary outcome) and pain (secondary outcome) before and after the sessions. Nurses will assess other secondary outcomes unblinded, i.e., perceived quality of life and NPS, both assessed with validated scales. The sleep duration will be indirectly assessed by a wrist device called MotionWatch. Information about psychotropic drug use will be derived from electronic medical chart review.

Discussion
The main purpose of this study is to assess the effects of individual music therapy on directly observed well-being controlled for individual attention in nursing home residents with dementia with NPS. The outcomes refer to both short-term and long-term effects consistent with therapeutic goals of care for a longer term. We hope to overcome limitations of previous study designs such as not blinded designs and music facilitators that were not only music therapists but also occupational therapists and nurses. This study should lead to more focused recommendations for practice and further research into non-pharmacological interventions in dementia such as music therapy.

Trial registration
The trial is registered at the International Clinical Trials Registry Platform (ICTRP) search portal in the Netherlands Trial Registration number NL7708, registration date 04-05-2019.
Epidemiological and clinical burden of Clostridioides difficile infections and recurrences between 2015 − 2019: the RECUR Germany study
Authors: Tricotel Aurore , Antunes Ana , Wilk Adrian , Dombrowski Silvia , Rinta-Kokko Hanna , Andersson Fredrik L. , Ghosh Subrata 
Published: March 2024

Abstract
Background
This real-world study assessed the epidemiology and clinical complications of Clostridioides difficile infections (CDIs) and recurrences (rCDIs) in hospital and community settings in Germany from 2015 − 2019.

Methods
An observational retrospective cohort study was conducted among adult patients diagnosed with CDI in hospital and community settings using statutory health insurance claims data from the BKK database. A cross-sectional approach was used to estimate the annual incidence rate of CDI and rCDI episodes per 100,000 insurants. Patients’ demographic and clinical characteristics were described at the time of first CDI episode. Kaplan-Meier method was used to estimate the time to rCDIs and time to complications (colonic perforation, colectomy, loop ileostomy, toxic megacolon, ulcerative colitis, peritonitis, and sepsis). A Cox model was used to assess the risk of developing complications, with the number of rCDIs as a time-dependent covariate.

Results
A total of 15,402 CDI episodes were recorded among 11,884 patients. The overall incidence of CDI episodes declined by 38% from 2015 to 2019. Most patients (77%) were aged ≥ 65 years. Around 19% of CDI patients experienced at least one rCDI. The median time between index CDI episode to a rCDI was 20 days. The most frequent complication within 12-months of follow-up after the index CDI episode was sepsis (7.57%), followed by colectomy (3.20%). The rate of complications increased with the number of rCDIs. The risk of any complication increased by 31% with each subsequent rCDI (adjusted hazard ratio [HR]: 1.31, 95% confidence interval: 1.17;1.46).

Conclusions
CDI remains a public health concern in Germany despite a decline in the incidence over recent years. A substantial proportion of CDI patients experience rCDIs, which increase the risk of severe clinical complications. The results highlight an increasing need of improved therapeutic management of CDI, particularly efforts to prevent rCDI.
Six-month binocular stereopsis recovery and its influencing factors in children with intermittent exotropia
Authors: Zhao Guohong , Fu Jing , Qi Yue , Wang Yidi , Wei Wenbin 
Published: March 2024

AbstractObjectiveTo investigate the recovery of binocular stereopsis recovery and its influencing factors in children with intermittent exotropia after successful correction of eye position.MethodsProspective clinical study. A total of 178 patients, aged 9 ∼ 14 (10.8 ± 1.7) years, who were successfully corrected after intermittent exotropia surgery at the Beijing Tongren Hospital Affiliated to Capital Medical University from October 2023 to September 2023 were collected, the follow-up duration was six-month or longer. Paired t test, Pearson correlation analysis and multivariable linear regression analysis were used to probe preoperative clinical features that may predict the stereopsis six months after surgery.ResultsSix months after surgery, the angle of deviation of the patients met the orthotopic standard, and there was significant difference compared with that before surgery (distant: -2.7△±3.2△vs. -30.5△±8.4△, t=-25.3,P < 0.001. Near:-3.7△±4.1△vs. -33.7△±8.0△, t=-26.1,P < 0.001). Distant stereopsis (3.0 ± 0.6 vs. 3.9 ± 0.4, t = 4.9,P < 0.05) and near stereopsis (2.3 ± 0.5 vs. 2.6 ± 0.4, t = 3.8,P < 0.05) were both significantly improved compared with that of before surgery. 17% and 22% patients rebuilt normal distant stereopsis and normal near stereopsis, respectively. Preoperative distant stereopsis (r=-0.26,P = 0.004) and near stereopsis (r=-0.23,P = 0.011) was significantly negatively correlated with convergence reserve. Multivariable analysis showed that patients’ age (β = 0.003,p = 0.037), anisometropia (β = 0.015,p = 0.043), and preoperative distant stereopsis (β = 0.456,p < 0.001) were significantly associated with postoperative distant stereopsis. Patients’ age (β = 0.005,p = 0.044), anisometropia (β = 0.127,p = 0.034), angle of deviation (β=-0.230,p = 0.020), and preoperative near stereopsis (β = 0.136,p < 0.001) were significantly associated with postoperative near stereopsis.ConclusionIXT patients could get eye position fixed after surgery, about 20% patients benefited from stereopsis improvement. Patient’s age, binocular anisometropia, angle of deviation and preoperative stereopsis were independent factors influencing postoperative stereopsis.
Psychometric evaluation of the Arabic language version of the Birchwood Insight Scale in patients with schizophrenia
Authors: Fekih-Romdhane Feten , Bitar Zeinab , Al Mouzakzak Fadila , Abilmona Ghinwa , Dahdouh Oussama , Hallit Souheil 
Published: March 2024

Abstract
Background
Clinical insight (i.e., impaired insight into illness) is increasingly recognized by the scientific community as a significant contributor to an array of psychological and clinical outcomes in schizophrenia. Therefore, its assessment using a reliable, rapid, easy and economic tool is important for clinical practice. This study proposes to investigate the psychometric properties of an Arabic translation of the Birchwood Insight Scale (BIS) in Arabic-speaking chronic patients with schizophrenia. Our objectives were to identify the most adequate factor structure of the BIS among the several measurement models previously proposed in the literature, verify the reliability and measurement invariance of the BIS across sex groups, and explore the concurrent validity of the BIS through examining its patterns of correlations with psychotic symptoms.

Method
One hundred seventeen Arabic-speaking chronic, remitted patients with schizophrenia took part in this study. An Arabic translated version of the BIS and the Positive and Negative Syndrome Scale (PANSS) were administered to participants.

Results
Confirmatory factor analyses (CFA) showed that, after omitting two items with low loadings (items 1 and 2), the unidimensional factor model of the BIS showed good fit indices and a reliability of α = 0.68 and ω = 0.68. However, analyses failed to show good fit for the full-length one-, two-, and three-factor models of the BIS in its Arabic version. Measurement invariance of the Arabic 6-item one-factor BIS was established between males and females at the configural, metric and scalar levels; no statistically significant difference between males and females was found in terms of BIS scores. Finally, BIS scores correlated significantly with the PANSS scores in our sample, thus demonstrating adequate concurrent validity.

Conclusion
This study offers valuable additional psychometric information about the BIS based on results of CFA and other analyses in schizophrenia from a non-Western cultural environment. We believe that making the BIS available in Arabic might benefit clinicians working with Arabic-speaking patients with schizophrenia, open new avenues of research and gain a better knowledge into the nature of clinical insight and its relevance to psychopathology.
A scoping review of continuing education models and statutory requirements for pharmacists globally
Authors: Ballaram Sholene , Perumal-Pillay Velisha , Suleman Fatima 
Published: March 2024

Abstract
Background
In the dynamic field of pharmacy amongst a diverse array of countries with disparate income levels, pharmacists play a pivotal role in integrating emerging scientific knowledge into their practice while adapting to evolving therapeutic interventions and expanding service delivery responsibilities. Lifelong Learning (LLL) is cultivated through continuing professional education (CPE) and continuing professional development (CPD), indispensable components ensuring sustained professional competence and heightened patient care quality. The global landscape witnesses diverse LLL activities tailored to pharmacists’ learning needs and preferences. This scoping review maps and synthesises a comprehensive global perspective on the existing knowledge regarding CPE/CPD models, statutory requirements, and pharmacists’ preferences for LLL activities.

Objective
To comprehensively investigate global models of CPE/CPD for pharmacists’ and examine the statutory requirements governing pharmacists’ registration and licensure.

Method
A literature search of PubMed, Google Scholar, Web of Science, and the University of KwaZulu-Natal library search engine was undertaken for studies between January 2012 and February 2023. The article selection and reporting followed the recommendations made by PRISMA (Preferred Reporting Items of Systematic Reviews and Meta-Analyses) guidelines. The articles were tabulated based on their respective country’s income level, continuing education models employed, country-specific statutory requirements, and pharmacists’ preferences for LLL activities.

Results
Of the initial 3974 publications identified through the database search, 24 studies met the review criteria. The majority of the articles originated from high-income countries (HICs) (14/24, 58.3%), and most employed the mandatory CPD points system (21/24, 87.5%). However, in some HICs and upper-middle income countries (UMICs), the CPE/CPD is non-mandatory. While most countries (19/24, 79.2%) offer various LLL formats, the preference of pharmacists remains primarily face-to-face learning (13/24, 54.2%). However, workplace learning (3/24, 12.5%) and blended learning (7/24, 29.1%) are mentioned in some studies.

Conclusion
Diverse models of CPE/CPD alongside statutory requirements persist globally and evolve, shaped by varied implementation experiences. HICs lead in CPD models, while the implementation in low- and middle-income countries (LMICs) and low-income countries (LICs) requires further exploration for inclusivity and effectiveness. A few UMICs are either initiating or in early stages of implementing the CPD models. Structured planning for LLL activities is increasingly a global requirement for pharmacists’ licensure. The essential progression of pharmacy practice in developing healthcare systems necessitates a mandatory CPD model. Ongoing research is crucial to fortify the implementation, align and unify the CPD model with evolving pharmacy profession needs.
How patients experience respect in healthcare: findings from a qualitative study among multicultural women living with HIV
Authors: Fernandez Sofia B. , Ahmad Alya , Beach Mary Catherine , Ward Melissa K. , Jean-Gilles Michele , Ibañez Gladys , Ladner Robert , Trepka Mary Jo 
Published: March 2024

Abstract
Background
Respect is essential to providing high quality healthcare, particularly for groups that are historically marginalized and stigmatized. While ethical principles taught to health professionals focus on patient autonomy as the object of respect for persons, limited studies explore patients’ views of respect. The purpose of this study was to explore the perspectives of a multiculturally diverse group of low-income women living with HIV (WLH) regarding their experience of respect from their medical physicians.

Methods
We analyzed 57 semi-structured interviews conducted at HIV case management sites in South Florida as part of a larger qualitative study that explored practices facilitating retention and adherence in care. Women were eligible to participate if they identified as African American (n = 28), Hispanic/Latina (n = 22), or Haitian (n = 7). They were asked to describe instances when they were treated with respect by their medical physicians. Interviews were conducted by a fluent research interviewer in either English, Spanish, or Haitian Creole, depending on participant’s language preference. Transcripts were translated, back-translated and reviewed in entirety for any statements or comments about “respect.” After independent coding by 3 investigators, we used a consensual thematic analysis approach to determine themes.

Results
Results from this study grouped into two overarching classifications: respect manifested in physicians’ orientation towards the patient (i.e., interpersonal behaviors in interactions) and respect in medical professionalism (i.e., clinic procedures and practices). Four main themes emerged regarding respect in provider’s orientation towards the patient: being treated as a person, treated as an equal, treated without blame or prejudice, and treated with concern/emotional support. Two main themes emerged regarding respect as evidenced in medical professionalism: physician availability and considerations of privacy.

Conclusions
Findings suggest a more robust conception of what ‘respect for persons’ entails in medical ethics for a diverse group of low-income women living with HIV. Findings have implications for broadening areas of focus of future bioethics education, training, and research to include components of interpersonal relationship development, communication, and clinic procedures. We suggest these areas of training may increase respectful medical care experiences and potentially serve to influence persistent and known social and structural determinants of health through provider interactions and health care delivery.