bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conflicting forces in the implementation of medicinal cannabis regulation in Uruguay
Authors: Alvarez Eliana , Queirolo Rosario , Sotto Belen 
Published: July 2023

Abstract
Background
Uruguay is widely known as a pioneer country regarding cannabis regulation policies, as it was the first state to regulate the cannabis market for both recreational and medicinal purposes in 2013. However, not all aspects of the regulation have moved forward at the same speed. Medicinal uses keep facing several challenges that undermine patients’ effective access to treatments and products. What are those persistent challenges for the medicinal cannabis policy in Uruguay? This paper aims to describe and understand the current state of medicinal cannabis in the country and identify the most critical challenges and conflicting forces for its proper implementation.

Methods
To do so, we conduct twelve in-depth interviews with key informants, including governments officials, activists, entrepreneurs, researchers, and doctors. These interviews are complemented with information from the congressional committees’ public records and other documentary sources.

Results
This research shows that the legal framework was thought to assure quality products over access. The main challenges of medicinal cannabis in Uruguay are related to three issues: (i) the timid development of the industry, (ii) a limited and expensive supply, and (iii) the emergence of an informal productive sector.

Conclusions
The political decisions regarding medicinal cannabis made in the last seven years have derived from a halfway policy that fails to guarantee patient access or promote the growth of a vibrant national industry. Positively, the several actors involved are aware of the extent of these challenges and new decisions have been made to overcome them, meaning that monitoring the future of the policy is very much needed.
Cannabis sativa demonstrates anti-hepatocellular carcinoma potentials in animal model: in silico and in vivo studies of the involvement of Akt
Authors: Akinloye Dorcas I. , Metibemu Damilohun S. , Shittu Mujidat T. , Lawal Mariam A. , Olatunji Faith O. , Oyediran Muideen A. , Akinloye Oluseyi A. 
Published: July 2023

Abstract
Background
Targeting protein kinase B (Akt) and its downstream signaling proteins are promising options in designing novel and potent drug candidates against hepatocellular carcinoma (HCC). The present study explores the anti-HCC potentials of Cannabis sativa (C. sativa) extract via the involvement of Akt using both in silico and in vivo animal models of HCC approaches.

Methods
Phytoconstituents of C. sativa extract obtained from Gas Chromatography Mass-spectrometry (GCSM) were docked into the catalytic domain of Akt-2. The Diethylnitrosamine (DEN) model of HCC was treated with C. sativa extract. The effects of C. sativa extract treatments on DEN model of hepatocellular carcinoma were assessed by One-way analysis of variance (ANOVA) of the treated and untreated groups

Result
The lead phytoconstituents of C. sativa extract, Δ-9-tetrahydrocannabinol (Δ-9-THC) and cannabidiol form stable hydrophobic and hydrogen bond interactions within the catalytic domain of Akt-2. C. sativa extract (15 mg/kg and 30 mg/kg) respectively gives a 3-fold decrease in the activities of liver function enzymes when compared with the positive control (group 2). It also gives a 1.5-fold decrease in hepatic lipid peroxidation and elevates serum antioxidant enzymes’ activities by 1-fold in HCC treated Wistar rats when compared with the positive control (group 2). In an animal model of hepatocellular carcinoma, C. sativa extract significantly downregulated Akt and HIF mRNAs in groups 3, 4, and 5 with 2, 1.5, 2.5-fold decrease relative to group 2. VEGF mRNA was downregulated by 1.5-fold decrease in groups 3-5 when compared to group 2. The expression of XIAP mRNA was downregulated by 1.5, 2, and 1.25-folds in groups 3, 4, and 5 respectively, in comparison with group 2. In comparison to group 2, COX-2 mRNA levels were downregulated by 1.5, 1, and 1-folds in groups 3–5. In groups 3–5, CRP mRNA was downregulated by 2-fold in comparison with group 2. In groups 3–5, p21 mRNA was upregulated by 2, 2.5, and 3-folds, respectively when compared with group 2. It upregulated p53 mRNA by 2.5, 3.5, and 2.5-folds in groups 3–5 in comparison with group 2. It downregulated AFP mRNA by 3.5, 2.5, .2.5-folds in groups 3, 4, and 5 respectively when compared with group 2. Histologic analysis showed that C. sativa extract reduced necrosis and inflammation in HCC.

Conclusion
C. sativa demonstrates anti-hepatocellular carcinoma potentials in an animal model of HCC and with the involvement of Akt. Its anticancer potential is mediated through antiangiogenic, proapoptotic, cycle arrest, and anti-inflammatory mechanisms.
In future studies, the mechanisms of anti-HCC effects of Δ-9-tetrahydrocannabinol (Δ-9- THC) and cannabidiol via the PI3K-Akt signaling pathways should be explored.
Characterization of blaTEM and blaCTX-M beta-lactam resistance genes in chronic rhinosinusitis
Authors: Arian Nejad Mojdeh , Sabaei Milad , Ahmadi Alireza , Minaeian Sara , Amin Panah Danesh , Mozahheb Yousefi Kimia 
Published: July 2023

Abstract
Background
Chronic sinusitis is one of the most challenging health problems of contemporary society. Although several treatment methods have been defined, a comprehensive understanding of the underlying causes (e.g., antibiotic resistance) is still elusive. The aim of this study was to characterize two of the main extended-spectrum beta-lactamase genes—i.e., blaTEM and blaCTX-M genes—and investigate antimicrobial resistance in bacteria isolated from chronic sinusitis. Samples from 70 chronic sinusitis patients and 20 healthy individuals (controls) were analyzed for the presence of blaTEM and blaCTX-M resistance genes using the polymerase chain reaction (PCR) test, followed by gene sequence analysis.

Results
Phenotypic and genotypic beta-lactam resistance was observed in 58.7% and 61.54% of the gram-negative isolates, respectively, with 38.46% carrying the blaTEM gene and 34.62% harboring the blaCTX-M gene. Sequencing data indicated high heterogeneity in blaCTX-M genes (69–100% similarity to reported sequences) and lower heterogeneity in blaTEM genes (93–99%).

Conclusion
Broad-spectrum beta-lactam resistance is a major pathogenesis factor in chronic rhinosinusitis, and careful consideration is required for antimicrobial therapy. High blaCTX-M heterogeneity could mean high horizontal transfer rate of this gene and warrant a surveillance program.
Effect of ovulation on postural sway in association with sex hormone variation across the menstrual cycle in college students: an observational study
Authors: Aziz Hager M. Abdel , Aziz Khadyga S. Abdel , Wahab Abd El Rahman H. Abd El , El-Shafei Manal A. 
Published: July 2023

Abstract

Background
Poor balance associated with increased postural sway is a risk factor for the high incidence of injuries found during specific menstrual cycle phases. This fact led to the hypothesis that female reproductive hormones affect soft tissue and neuromuscular function, reducing postural balance and resulting in a high injury prevalence among female college students. So, the current study aimed to identify the influence of ovulation in association with sex hormone variation across the menstrual cycle on postural sway in college students.

Material and methods
Forty female college students were enrolled in this study. They were recruited among physical therapy students at Deraya University, New Minya, Egypt. They were aged from 17 to 22 years. They were allocated to a single group. Progesterone and estradiol blood levels were measured to detect the timing of the follicular and luteal phases, and a urine luteinizing hormone (LH) strip test was used to determine when ovulation occurred. The dynamic postural sway index was assessed by using the Biodex Balance system. All measurements were taken on the early follicular (1st–3rd) day, the ovulatory (11th–13th) day, and the mid-luteal phase (21st–23rd) day from the onset of menstruation.

Results
Statistical analysis showed that the anteroposterior, mediolateral, and overall sway index increased significantly during the ovulatory phase compared to the earlier follicular and mid-luteal menstrual cycle phases in female college students (P < 0.05). There was no significant variance between the early follicular and mid-luteal phases (P > 0.05).

Conclusions
It can be concluded that increased female sex hormones during ovulation affect postural sway, which may disturb balance and increase the risk of injuries in college students.
End-user acceptability of a prototype digital stethoscope to diagnose childhood pneumonia- a qualitative exploration from Sylhet, Bangladesh
Authors: Joarder Taufique , Tune Samiun Nazrin Bente Kamal , Islam ASMD Ashraful , Islam Arifa , Roy Arunangshu Dutta , McCollum Eric D. , Nair Harish , Cunningham Steven , McLane Ian Mitra , Shahidullah Mohammod , Baqui Abdullah H. , Ahmed Salahuddin 
Published: July 2023

Abstract
Background
Considering the high frequency of respiratory infections among children in low- and middle-income countries (LMICs), the World Health Organization (WHO) developed a pragmatic guideline for managing pneumonia in low-resource settings. The guideline’s low specificity leads to many false-positive pneumonia cases receiving antibiotic treatment. Integrating diagnostic technology to incorporate lung sounds into WHO guidelines could improve childhood pneumonia diagnosis and management. This qualitative study aimed to explore the acceptability of a prototype digital stethoscope device among potential end-users in Bangladesh.

Methods
We conducted four focus group discussions (FGDs) with beneficiaries and service providers who used a 2018 digital stethoscope prototype. The data collection was conducted in November 2020. The study was carried out at Zakiganj Upazila (sub-district) of Sylhet district of Bangladesh. A total of 34 respondents, including parents of under-5 children, Community Health Care Providers (CHCPs), and community leaders were enrolled. Two researchers (TJ and a research assistant (not a co-author of this manuscript) conducted the FGDs. Verbatim transcripts were prepared, and translations were completed. Coding was executed in Microsoft Excel, and relevant quotes were extracted to ascertain the emerging themes. To ensure validity, two researchers coded the dataset independently and inconsistencies were resolved through discussion.

Findings
Mothers were more aware of the digital stethoscope than fathers. Except for the female community leaders, male leaders were unaware of the stethoscopes. Most CHCPs had positive perceptions of the digital stethoscope. They appreciated stethoscope training as they learned about new technology and diagnostic approaches. The users mentioned several technical shortcomings of the prototype device. A few stakeholders expressed dissatisfaction with the level of community involvement and information sharing from the study. The use of the device plummeted during the COVID-19 pandemic for fear of infection, to counteract which the CHCPs cleaned the device with chlorhexidine after every application as a precaution.

Conclusion
Overall, device use was supported by stakeholders despite perceptions that the prototype had some technological limitations, community engagement was suboptimal, and the COVID-19 pandemic caused disruptions. Stronger community engagement, addressing technological issues, and further research on its health systems application would improve the acceptability and effective use of the digital stethoscope.
Automated Classification of Breast Cancer Across the Spectrum of ERBB2 Expression Focusing on Heterogeneous Tumors With Low Human Epidermal Growth Factor Receptor 2 Expression
Authors: Guvakova Marina A. 
Published: July 2023

PURPOSE Although pharmaceutical companies conduct clinical trials of novel human epidermal growth factor receptor 2 (HER2)-low–directed drugs, diagnosing HER2-low cancer by immunohistochemistry (IHC) and in situ hybridization (ISH) remains challenging. This study investigates the performance of first-in-kind computerized intelligence to classify samples across gene expression levels and differentiate HER2-low tumors. MATERIALS AND METHODS We classified 251 samples: 142 primary invasive breast cancers (IBCs), 75 ductal carcinomas in situ (DCIS), and 34 mammaplasties (reference) using mRNA expression data from the QuantiGene Plex 2.0 assay. We used g3mclass probabilistic software to assess the number of classes in the assay data, the mean and the variance in each class, diagnostic cutoffs, and the prevalence of each class in the study population. RESULTS HER2-low (IHC score of 1+ or 2+/ISH–) accounted for 31% of IBC. First, we discovered that HER2-low tumors were represented by cases with normal ERBB2 transcript levels that were expected to produce physiologic levels of HER2 (70%) and cases with abnormally upregulated unamplified ERBB2 (30%). We termed the latter cancers ERBB2-up as they do not meet the standard definitions for ERBB2 overexpression and amplification. Second, HER2-low IBC classified as ERBB2-up had not only abnormally increased luminal growth and adhesion markers ( ERBB2, ESR1, PGR, IGF1R, VAV2, VAV3, KRT8, CDH1) but also downregulated myoepithelial marker ( KRT5). The vascularization ( RAP1 and C3G), immune cell infiltration ( VAV1), and mesenchymal transition ( CDH2) markers were dysregulated. Finally, in the independent cohort of DCIS, 40% of HER2-low DCIS shared similar traits with HER2-low IBC except for rare downregulation of KRT5 and no change in C3G, VAV1, and CDH2. CONCLUSION We demonstrated how innovative bioinformatic tools could help diagnose cancer across the spectrum of ERBB2 expression to aid decision making for HER2-low.
Comparison of Olympic-Style Weightlifting Performances of Elite Athletes: Scaling Models Account for Body Mass
Authors: HUEBNER MARIANNE , MELTZER DAVID E. , BJARNASON ÁSGEIR , PERPEROGLOU ARIS 
Published: July 2023

ABSTRACT

Purpose
We developed a scale for comparison of performances by weightlifters of different body mass and compare this scaling formula to current systems.

Methods
Data from Olympics and World and Continental Championships from 2017 to 2021 were obtained; results from athletes with doping violations were excluded, resulting in performances from 1900 athletes from 150 countries for use in analysis. Functional relationships between performance and body mass were explored by testing various transformations of body mass in the form of fractional polynomials that include a wide range of nonlinear relationships. These transformations were evaluated in quantile regression models to determine the best fit, examine sex differences, and distinguish fits for different performance levels (90th, 75th, and 50th percentiles).

Results
The resulting model used a transformation of body mass with powers −2 and 2 for males and females and was used to specify a scaling formula. The small percentage deviations between modeled and actual performances confirm the high accuracy of the model. In the subset of medalists, scaled performances were comparable across different body masses, whereas both Sinclair and Robi scalings, currently used in competitions, were more variable. The curves had similar shapes for the 90th and 75th percentile levels but were less steep for the 50th percentile.

Conclusions
The scaling formula we derived to compare weightlifting performances across a range of body mass can easily be implemented in the competition software to determine the overall best lifters. This is an improvement over current methods that do not accurately account for differences in body mass and result in bias or yield large variations even with small differences in body mass despite identical performances.
Use of whole exome sequencing for identification of genetic variants related to Growth Hormone Deficiency and Short Stature: A Family-Based Study
Authors: Alharazy Shatha , Naseer Muhammad Imran 
Published: July 2023

Objective: Genetic polymorphisms in genes involved in growth process and Vitamin-D metabolism form a significant etiology behind growth hormone deficiency and short stature. The aim of this study was to explore for known and unknown genes and variants related to growth hormone and short stature in a family based study using whole exome sequencing (WES).
Method: This family-based study included a family with members diagnosed with growth hormone deficiency, short stature and Vitamin-D deficiency (four boys affected and four boys non-affected). The participants were recruited from King Abdulaziz University Hospital (Jeddah, Saudi Arabia) and referred to King Fahad Centre for Medical Research (Jeddah, Saudi Arabia from April 2022 to June 2022. The consanguineous parents and one of the affected boys (aged 16 years old) underwent WES.
Results: Several variants in RNPC3, ACAN, GC, VDR and LRP2 were identified in index cases but not in controls. Novel frameshift and splice region variants in RNPC3 (c.358dupA, p.Arg120fs) were detected. Other missense variants were also observed including variants in ACAN (c.2591C>T, c.2789G>T, c.2815T>A, c.4207A>G, c.4523A>C and c.7119C>G), GC (rs4588 and rs7041) and LRP2 (rs2075252 and rs1991517). A start loss variant in VDR (rs2228570) with high impact was also observed.
Conclusions: Our findings suggest a potential association of these variants with growth hormone deficiency and short stature. In this study, novel pathogenic variants in RNPC3 were revealed as well as other variants in ACAN and in genes related to Vitamin-D metabolism (GC, VDR and LRP2) that some or all might be associated with growth hormone deficiency. Further large-scale studies are required to address the association of these variants with growth hormone deficiency and its subsequent short stature.
doi: https://doi.org/10.12669/pjms.39.5.7601
How to cite this: Alharazy S, Naseer MI. Use of whole exome sequencing for identification of genetic variants related to Growth Hormone Deficiency and Short Stature: A Family-Based Study. Pak J Med Sci. 2023;39(5):---------. doi: https://doi.org/10.12669/pjms.39.5.7601
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Foreign bodies inside us - Trends and knowledge regarding long-acting reversible contraceptives (LARCs) use, factors influencing of contraceptives choice-making process, and the dual-method use among Polish college-aged women
Authors: Nowak Aleksandra , Nowak Alicja , Kiełbowicz Magdalena 
Published: July 2023

Introduction: The choice-making process of the contraceptive method seems complex and influenced by many factors. Long-acting reversible contraceptives require mechanical interference with the woman's body. For some, it will be an insurmountable barrier whilst for others a chance to enjoy a successful sex life without fear of pregnancy. Recognizing the factors influencing their use will allow us to identify target groups, increase awareness, and spread knowledge about them.
Purpose: This study aimed to assess contraceptive use trends and knowledge, focusing on long-acting reversible contraceptives (LARCs) and vaginal rings, also to identify predictors associated with their use and analyze the decision-making process for dual-method use (hormonal plus barrier method) among female college students in Poland.
Materials and methods: A self-administered questionnaire including 44 questions in the form of a web-based survey distributed among peers in social media platforms and forums.
Results: In the survey a total of 700 female students aged 19±25 took part. All the questions about LARC and vaginal rings were answered correctly by only 19 participants (2.71%). The most knowledgeable were medical students (p<0.0001). Out of 55 LARC and vaginal ring users (7.86%), 47 female students (76.4%,) stated the improvement of their life. Of the methods interfering with the body, the study group most frequently chose the vaginal ring (38.1%) and least frequently the hormone injection (0.1%).
Conclusions: Participants’ knowledge of LARC methods and vaginal rings is insufficient and its main influencing factors are faculty type and frequency of intercourse. LARC and vaginal disc are not the first contraception choice. Fear of pregnancy is the most common factor for dual method use.
Estratégias de educação em saúde nos anos iniciais do Ensino Fundamental: um estudo de revisão integrativa
Authors: Engers Patrícia Becker , Copetti Jaqueline , Graup Susane , Ilha Phillip Vilanova 
Published: July 2023

Historicamente, os campos da educação e da saúde estão interligados em busca de melhores condições de vida para a sociedade. Neste sentido, é importante que a educação em saúde seja abordada desde a infância, a fim de promover conhecimento e reflexões sobre a temática e sua dinamicidade. O objetivo do presente estudo foi revisar as publicações científicas relacionadas a educação em saúde nos anos iniciais do Ensino Fundamental. Para tanto, a revisão da literatura recorreu as bases de dados eletrônicas Pubmed, SciELO, Biblioteca Virtual em Saúde (Lilacs e Medline) e Periódicos Capes como fonte de pesquisa. Foram utilizados os descritores educação em saúde, saúde na escola, promoção da saúde, escolares e anos iniciais, para busca. A seleção dos artigos teve como critérios de inclusão: artigos originais de estudos realizados no Brasil e publicados nas línguas português, inglês e espanhol, no intervalo de 2004 a 2019. Foram incluídos 23 estudos na presente revisão. Os temas relacionados a educação em saúde mais recorrentes foram a educação alimentar e nutricional e a educação postural. Quanto às estratégias de ensino para a temática pesquisada, foi possível inferir que a maioria das ações adotam estratégias de caráter lúdico. Conclui-se que o desenvolvimento da temática educação em saúde nos anos iniciais do Ensino Fundamental ainda ocorre de forma pontual e na maioria das vezes conduzidos pelos profissionais da saúde, sendo necessário que a saúde faça, efetivamente, parte do currículo escolar, para que sua abordagem se torne mais efetiva e promova resultados permanentes.