bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of two protocols for the generation of iPSC-derived human astrocytes
Authors: Mulica Patrycja , Venegas Carmen , Landoulsi Zied , Badanjak Katja , Delcambre Sylvie , Tziortziou Maria , Hezzaz Soraya , Ghelfi Jenny , Smajic Semra , Schwamborn Jens , Krüger Rejko , Antony Paul , May Patrick , Glaab Enrico , Grünewald Anne , Pereira Sandro L. 
Published: September 2023

AbstractBackgroundAstrocytes have recently gained attention as key contributors to the pathogenesis of neurodegenerative disorders including Parkinson’s disease. To investigate human astrocytes in vitro, numerous differentiation protocols have been developed. However, the properties of the resulting glia are inconsistent, which complicates the selection of an appropriate method for a given research question. Thus, we compared two approaches for the generation of iPSC-derived astrocytes. We phenotyped glia that were obtained employing a widely used long, serum-free (“LSF”) method against an in-house established short, serum-containing (“SSC”) protocol which allows for the generation of astrocytes and midbrain neurons from the same precursor cells.ResultsWe employed high-content confocal imaging and RNA sequencing to characterize the cultures. The astrocytes generated with the LSF or SSC protocols differed considerably in their properties: while the former cells were more labor-intense in their generation (5 vs 2 months), they were also more mature. This notion was strengthened by data resulting from cell type deconvolution analysis that was applied to bulk transcriptomes from the cultures to assess their similarity with human postmortem astrocytes.ConclusionsOverall, our analyses highlight the need to consider the advantages and disadvantages of a given differentiation protocol, when designing functional or drug discovery studies involving iPSC-derived astrocytes.
Genome-wide identification, phylogenetic and expression pattern analysis of HSF family genes in the Rye (Secale cereale L.)
Authors: Ren Yanyan , Ma Rui , Xie Muhua , Fan Yue , Feng Liang , Chen Long , Yang Hao , Wei Xiaobao , Wang Xintong , Liu Kouhan , Cheng Peng , Wang Baotong 
Published: September 2023

Abstract
Background
Heat shock factor (HSF), a typical class of transcription factors in plants, has played an essential role in plant growth and developmental stages, signal transduction, and response to biotic and abiotic stresses. The HSF genes families has been identified and characterized in many species through leveraging whole genome sequencing (WGS). However, the identification and systematic analysis of HSF family genes in Rye is limited.

Results
In this study, 31 HSF genes were identified in Rye, which were unevenly distributed on seven chromosomes. Based on the homology of A. thaliana, we analyzed the number of conserved domains and gene structures of ScHSF genes that were classified into seven subfamilies. To better understand the developmental mechanisms of ScHSF family during evolution, we selected one monocotyledon (Arabidopsis thaliana) and five (Triticum aestivum L., Hordeum vulgare L., Oryza sativa L., Zea mays L., and Aegilops tauschii Coss.) specific representative dicotyledons associated with Rye for comparative homology mapping. The results showed that fragment replication events modulated the expansion of the ScHSF genes family. In addition, interactions between ScHSF proteins and promoters containing hormone- and stress-responsive cis-acting elements suggest that the regulation of ScHSF expression was complex. A total of 15 representative genes were targeted from seven subfamilies to characterize their gene expression responses in different tissues, fruit developmental stages, three hormones, and six different abiotic stresses.

Conclusions
This study demonstrated that ScHSF genes, especially ScHSF1 and ScHSF3, played a key role in Rye development and its response to various hormones and abiotic stresses. These results provided new insights into the evolution of HSF genes in Rye, which could help the success of molecular breeding in Rye.
Clinical manifestation, staging and prognosis of hepatocellular carcinoma in Gambian patients
Authors: Bittaye Sheikh Omar , Kambi Abubacarr , Tekanyi Momodou A. I. , Tamba Saydiba , Sanneh Lamin , Sisawo Momodou Musa , Jatta Abdoulie , Fatty Gibril , Jeng Adam , Jallow Momodou Salieu , Leigh Ousman , Njie Ramou 
Published: September 2023

Abstract
Background
As a result of the lack of screening programs and the difficulty in making a proper diagnosis, the majority of hepatocellular carcinoma (HHC) patients present late in low-resource countries. The study therefore assesses the clinical features, stage and prognostic variables of patients with HCC in The Gambia.

Methods
From December 2015 to January 2019, patients with a confirmed diagnosis of HCC were enrolled. All patients’ medical history, ultrasound scan, FibroScan and laboratory details were collected.

Results
Two hundred and sixty (260) patients were enrolled. The mean age of HCC patients was 40 years, and 210 (80.7%) of them were male. The most common gastrointestinal symptoms were early satiety 229 (88.1%) and abdominal pain 288 (87.7%), while the most common constitutional symptoms were weight loss 237 (91.2%) and easy fatiguability 237 (91.2%). Hepatomegaly 205 (78.8%) was the most common sign. On ultrasound scan, lesions were mostly multifocal 175 (67.3%), and the median FibroScan score was 75 kPa. The median fibrosis 4 and aspartate transferase platelet ratio index were 4.6 and 2.2, respectively. Hepatitis B surface antigen (HBsAg) was positive in 170 (65.4%) patients, and the median AFP level was 3263 ng/ml. HCC patients with positive HBsAg were more likely to be male 145 (85.3%) vs 62 (72.1%) (p = 0.011), much younger 39.9 vs 51.4 yrs (p =  < 0.0001), more likely to have abdominal pain 156 (91.8%) vs 68 (79.1%) (p = 0.002), jaundice 78 (45.9%) vs 29 (33.7%) (p = 0.042), dark urine 117 (68.8%) vs 46 (53.5%) (p = 0.018), raised transaminases (Aspartate transaminases 224.5 (32–7886) vs 153 (18–610), p =  < 0.01, Alanine transferases 71 (5–937) vs 47 (8–271), p =  < 0.001) and decreased platelet count 207 (33–941) vs 252 (52- 641) (p = 0.021) compared to patients with HCC who were HBsAg-negative.

Conclusions
The prognosis of patients with HCC is poor in developing countries such as The Gambia, where screening programs and treatment modalities are scarce. Young males are disproportionately affected, and HBV is a major cause of HCC in The Gambia.
Polymorphism at codon 31 of CDKN1A (p21) as a predictive factor for bevacizumab therapy in glioblastoma multiforme
Authors: Cheng Wen-Yu , Shen Chiung-Chyi , Liang Yea-Jiuen , Chiao Ming-Tsang , Yang Yi-Chin , Hsieh Wan-Yu , Lin Cheng-Hui , Chen Jun-Peng 
Published: September 2023

AbstractGlioblastoma (GBM), a prevalent and malignant brain tumor, poses a challenge in surgical resection due to its invasive nature within the brain parenchyma. CDKN1A (p21, Waf-1), a cyclin-dependent kinase inhibitor, plays a pivotal role in regulating cell growth arrest, terminal differentiation, and apoptosis. The existence of natural variants of CDKN1A has been associated with specific cancer types. In this retrospective study, our objective was to identify polymorphic variants of CDKN1A, specifically c.93C > A (codon 31 Ser31Arg), and investigate its potential impact within the scope of bevacizumab therapy for glioblastoma multiforme. This study involved a cohort of 139 unrelated adult Chinese GBM patients in Taiwan. Genomic DNA extracted from tumor samples was utilized for genotyping using the polymerase chain reaction (PCR) restriction fragment length polymorphism method (PCR–RFLP analysis). Through unconditional logistic regression analysis, odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Our findings unveiled that among these GBM patients, the distribution of codon 31 polymorphisms was as follows: 23.02% were Serine homozygotes (Ser/Ser), 27.34% were Arginine homozygotes (Arg/Arg), and 49.64% were Serine/Arginine heterozygotes (Ser/Arg). While CDKN1A c.93C > A polymorphisms did not exhibit a direct association with overall survival in GBM patients, noteworthy survival benefits emerged among individuals with Arg/Arg and Arg/Ser genotypes who received combined concurrent chemoradiotherapy (CCRT) and bevacizumab treatment compared to those who underwent CCRT alone. Our findings indicate a significant involvement of the CDKN1A c.93C > A polymorphism in the development and onset of GBM, offering potential implications for the early prognostication of bevacizumab therapy outcomes.
Corrected analysis of “the effects of bright light treatment on affective symptoms in people with dementia: a 24-week cluster randomized controlled trial” that accounts for clustering and nesting verifies conclusions
Authors: Jamshidi-Naeini Yasaman , Golzarri-Arroyo Lilian , Siddique Abu Bakkar , Vorland Colby J. , Rodriguez Miriam Jocelyn , Holden Richard J. , Allison David B. 
Published: September 2023

AbstractIn this correspondence, we explain the reasoning for invalidity of the analysis choices by Kolberg et al., and provide the results produced using correct statistical procedures for their study design. Reassuringly, we could verify the original conclusions. That is, results of the corrected statistical models are similar to the results of the original analysis. Regardless of the magnitude of difference that corrected statistical methods make, results and conclusions that are derived from invalid methods are unsubstantiated. By verifying the results, we allow the readers to be assured that the published conclusions in the study by Kolberg et al. now rest on a sound evidential basis.
Effect of short implant crown-to-implant ratio on stress distribution in anisotropic bone with different osseointegration rates
Authors: Yuan Xi , Liu Yuchen , Yang Yunhe , Ren Mingfa , Luo Lailong , Zheng Lang , Liu Yang 
Published: September 2023

Abstract
Objective
This study aimed to provide evidence for the clinical application of single short implants by establishing an anisotropic, three-dimensional (3D) finite element mandible model and simulating the effect of crown-to-implant ratio (CIR) on biomechanics around short implants with different osseointegration rates.

Methods
Assuming that the bone is transversely isotropic by finite element method, we created four distinct models of implants for the mandibular first molar. Subsequently, axial and oblique forces were applied to the occlusal surface of these models. Ultimately, the Abaqus 2020 software was employed to compute various mechanical parameters, including the maximum von Mises stress, tensile stress, compressive stress, shear stress, displacement, and strains in the peri-implant bone tissue.

Results
Upon establishing consistent osseointegration rates, the distribution of stress exhibited similarities across models with varying CIRs when subjected to vertical loads. However, when exposed to inclined loads, the maximum von Mises stress within the cortical bone escalated as the CIR heightened. Among both loading scenarios, notable escalation in the maximum von Mises stress occurred in the model featuring a CIR of 2.5 and an osseointegration rate of 25%. Conversely, other models displayed comparable strength. Notably, stress and strain values uniformly increased with augmented osseointegration across all models. Furthermore, an increase in osseointegration rate correlated with reduced maximum displacement for both cortical bone and implants.

Conclusions
After fixing osseointegration rates, the stress around shorter implants increased as the CIR increased under inclined loads. Thus, the effect of lateral forces should be considered when selecting shorter implants. Moreover, an implant failure risk was present in cases with a CIR ≥ 2.5 and low osseointegration rates. Additionally, the higher the osseointegration rate, the more readily the implant can achieve robust stability.
Preliminary in vitro cytotoxic evaluation of Uncaria gambier (Hunt) Roxb extract as a potential herbal-based pulpotomy medicament
Authors: Tan Bee Chin , Mahyuddin Alida , Sockalingam S. Nagarajan M. P. , Zakaria Ahmad Shuhud Irfani 
Published: September 2023

Abstract
Background
The downfall of formocresol as a pulpotomy medicament highlights the importance of cytotoxic evaluation and the establishment of a safe concentration of dental material prior to its usage in the oral cavity. Uncaria gambir is an herbal plant that possesses antimicrobial, anti-inflammatory and antioxidant properties, suggesting its potential as an alternative medicament for pulpotomy. However, there are not many studies published on its cytotoxicity, with some using non-standardised techniques and reported variable outcomes. Here, we investigated the concentration and time-dependent toxicity of Uncaria gambir extract towards the M3CT3-E1 cell line and compared it with the gold standard pulpotomy medicament: mineral trioxide aggregate (MTA).

Methods
Uncaria gambir extracts at concentrations ranging from 1000 to 7.8 µg/ml and MTA eluates at 4- and 48 h setting times were prepared. 10% dimethyl sulfoxide (DMSO) and culture media were used as positive and negative controls respectively. Cell viability on days 1, 2, 3 and 7 was analysed using Alamar Blue and Live and Dead Cell assay. Any morphological cellular changes were evaluated using transmission electron microscopes (TEM). Data were analysed using a two-way mixed Analysis of Variance (ANOVA).

Results
The interaction between the concentration and exposure time on the fluorescence intensity of Uncaria gambir extract and MTA 48 h was found to be statistically significant (p < 0.001). No cytotoxic effects on the cells were exerted by both MTA 48 h and Uncaria gambir extract at a concentration below 500 µg/mL. TEM analysis and Live and Dead Cell assay for both materials were comparable to the negative control. No significant differences in fluorescent intensity were observed between Uncaria gambir extract at 500 µg/mL and MTA 48 h (p > 0.05).

Conclusion
Uncaria gambir extracts at a maximum concentration of 500 μg/mL are non-cytotoxic over time and are comparable to the MTA.
Providing culturally responsive care in a pediatric setting: are our trainees ready?
Authors: Chen Anna , Blatman Zachary , Chan Amy , Hossain Anna , Niles Chavon , Atkinson Adelle , Narang Indra 
Published: September 2023

Abstract
Background
Extensive data consistently demonstrates inequities in access and delivery of healthcare for patients from historically marginalized populations, resulting in poorer health outcomes. To address this systemic oppression in healthcare, it is necessary to embed principles of equity, diversity, and inclusion (EDI) at an early stage within medical education. This study aimed to assess pediatric trainees’ perceived interest in EDI curricula as well as their confidence in applying this knowledge to provide culturally responsive care.

Methods
An anonymous online survey was distributed to pediatric trainees at the University of Toronto. Closed-ended questions used a Likert scale to assess respondents’ confidence and interest in providing culturally responsive care to patients. Open-ended questions explored trainees’ perceptions of effective EDI learning modalities. A mixed methods approach was utilized, where quantitative data was summarized using descriptive statistics and descriptive content analysis was used to highlight themes within qualitative data.

Results
116 pediatric trainees completed the survey, of which 72/116 (62%) were subspecialty residents/fellows and 44/116 (38%) were core residents. 97% of all responses agreed or strongly agreed that it was important to learn about providing culturally responsive care to patients from historically marginalized communities; however, many trainees lacked confidence in their knowledge of providing culturally responsive care (42%) and applying their knowledge in clinical practice (47%). Respondents identified direct clinical exposure through rotations, immersive experiences, and continuity clinics as effective EDI teaching modalities. Identified barriers included time constraints in the clinical environment, burnout, and lack of exposure to diverse patient populations.

Conclusion
Most pediatric trainees want to provide culturally responsive care to patients from historically marginalized communities, but do not feel confident in their knowledge to do so. Trainees value learning about EDI through direct clinical exposure and immersive experiences, rather than didactic lectures or modules. These study findings will be utilized to develop and implement an enhanced EDI education curriculum for pediatric trainees at the University of Toronto and other postgraduate residency programs.
Factors associated with intention of clinical pharmacists and candidates to provide pharmaceutical care: application of theory planned behaviour
Authors: Tecen-Yucel Kamer , Ozdemir Nesligul , Kara Emre , Demirkan Kutay , Sancar Mesut , Okuyan Betul 
Published: September 2023

Abstract
Background
Postgraduate education programs in clinical pharmacy have become widespread in Türkiye. This study aimed to identify factors associated with the intention of Turkish clinical pharmacists and candidates (who were graduates and students of postgraduate clinical pharmacy programs) to provide pharmaceutical care.

Methods
This prospective observational study was conducted between June 2021 and May 2022. After searching relevant studies, an expert panel discussion, translation, cultural adaptation, and a pilot study developed a 52-item Turkish scale based on the Theory of Planned Behavior (TBP). Cronbach alpha for each construct was calculated after an explanatory factor and test–retest reliability analysis. An online survey link was sent to all graduates or candidates of postgraduate clinical pharmacy programs in Türkiye. After univariate regression analysis, the multiple linear regression model was performed.

Results
One hundred fifty-six participants completed the survey (response rate: 59.1%). The Cronbach’s alpha for attitude (9 items), subjective norm (6 items), perceived behavioural control (5 items), self-efficacy (6 items), intention (11 items) and past behaviour (15 items) were 0.945, 0.720, 0.751, 0.864, 0.934 and 0.955 respectively. The multiple linear regression analysis found a higher score of the subjective norm (p = 0.016), a higher score of self-efficacy (p < 0.001), younger age (p < 0.001) and having PhD (p = 0.038) were associated with increased intention score.

Conclusions
It was shown that higher self efficacy and positive beliefs of their peers and other healthcare professionals were associated with their higher intention score for providing pharmaceutical care. Younger age and having a PhD were other factors associated with their intention to provide pharmaceutical care.
The impact of journal clubs on postgraduate medical education in China
Authors: Li Yujuan , Zhang Yue , Liu Rong , Hao Yi , Xiong Jing 
Published: September 2023

Abstract
Purpose
Journal clubs hold significant importance in medical education, with numerous studies highlighting their contributions worldwide. However, studies specifically examining their role in China, particularly among Chinese medical postgraduates categorized into academic and clinical types, remain scarce. This research aims to investigate the participation, performance, and benefits of journal clubs, and explore the influence of student type and study phase on these aspects.

Method
A survey encompassing demographic information, participation rates, performance evaluations, and perceived improvements was distributed to postgraduates at Tongji Medical College of Huazhong University of Science and Technology. A total of 232 completed questionnaires were included for further analysis. Statistical analysis employed the Mann–Whitney U test and Gamma tests, with statistical significance set at p-value < 0.05.

Results
Overall participation and performance in journal clubs among Chinese medical postgraduates were comparable to global findings. Notably, academic postgraduates exhibited higher levels of attendance rate and gained more research assistance than clinical postgraduates, while their performance levels were similar. When considering the study phase, a downward trend in academic postgraduates' attendance rate and listening attitude and an upward trend in clinical postgraduates' participation were observed with the seniority phase. Additionally, presentation comments, post-presentation progress, and research assistance showed improvements over time for both student types.

Conclusions
This study reveals academic postgraduates' fatigue, contrasting with clinical postgraduates' enthusiasm, and underscores academic postgraduates' superior research assistance. To address these findings, we recommend supporting and encouraging scientific research training for clinical postgraduates, aiding academic postgraduates in better time management and reducing non-essential responsibilities, and implementing critical appraisal skill education.
Prospective prescription review system correlated with more rational PPI medication use, better clinical outcomes and reduced PPI costs: experience from a retrospective cohort study
Authors: Fan Xiucong , Chen Danxia , Bao Siwei , Dong Xiaohui , Fang Fang , Bai Rong , Zhang Yuyi , Zhang Xiaogang , Tang Weijun , Ma Yabin , Zhai Xiaobo 
Published: September 2023

Abstract
Introduction
Proton pump inhibitor (PPI) abuse poses an overwhelming threat to the allocation of medical resources and places a heavy burden on global medical expenses. In this study, we put forward our prospective prescription review system and evaluated the effects of this system on clinical outcomes, rational medication use and costs related to PPIs.

Methods
A retrospective cohort study was conducted in which the included patients were divided into a preintervention group (2019.10–2020.09) and a postintervention group (2020.10–2021.09). To reduce the bias of patients’ baseline characteristics, the propensity score matching (PSM) method was employed. The primary endpoints were the incidence of stress ulcers (SUs), the improvement and cure rates of gastrointestinal haemorrhage, the defined daily dose (DDD), the drug utilization index (DUI) and the DDD/100 patient-days. The secondary endpoints included the types of unreasonable medication orders for PPIs, the PPI utilization rate and PPI costs.

Results
A total of 53,870 patients were included to evaluate the secondary endpoints, and 46,922 patients were paired by PSM and assessed to evaluate the primary endpoints. The number of PPIs used and PPI costs were significantly lower in the postintervention group than in the preintervention group (P < 0.001). The rationality evaluation results showed that the frequency of PPI use and the number of drug interactions were significantly higher in the preintervention group than in the postintervention group (P < 0.01). The proportion of patients taking oral PPIs was significantly increased in the postintervention group (29.30% vs. 34.56%, p < 0.01). For the utilization of PPIs both for prevention and treatment, the DUI and DDD/100 patient-days were substantially decreased in the postintervention group (P < 0.001 and P < 0.05, respectively). The incidence of SUs in the postintervention group was 44.95%, and that in the preintervention group was 51.93% (p < 0.05).

Conclusion
The implementation of the prospective prescription review system on rational PPI use correlated with reduced PPI costs, more rational PPI medication use and better clinical outcomes, and this system is worthy of long-term implementation for further improvement of rational drug use.