bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence, associated factors and antimicrobial susceptibility patterns of Salmonella and Shigella species among diarrheic under five children in Sultan Sheik Hassan Yabere referral Hospital, Jigjiga, Eastern Ethiopia
Authors: Muse Kader , Urgessa Kedir , Shume Tadesse , Tahir Bawlah , Weldegebreal Fitsum 
Published: May 2024

Abstract
Background
Diarrhea caused by Salmonella and Shigella species are the leading cause of illness especially in developing countries. These infections are considered as the main public health problems in children, including Ethiopia. This study aimed to assess the prevalence, associated factors, and antimicrobial susceptibility patterns of Salmonella and Shigella species in Sheik Hassan Yabere Referral Hospital Jigjiga, Eastern Ethiopia from August 05 to November 15, 2022.

Method
A cross-sectional study was conducted among 239 under-five children with diarrhea selected through a convenient sampling technique. A structured questionnaire was used to collect associated factors. A stool sample was collected and processed for the identification of Salmonella and Shigella species using MacConkey adar, Xylose Lysine Deoxycholate agar (Oxoid Ltd) and Biochemical tests. The antimicrobial susceptibility pattern of isolates was performed using the Kirby-Bauer disc diffusion technique. The data was entered into Epi-data version 4.6 and exported to the statistical package of social science version 22 for analysis. The association between outcome and independent variables was assessed using bivariate, multivariable, and chi-square and P-value < 0.05 was considered as statistical significance.

Result
Overall prevalence of Salmonella and Shigella species was 6.3% (95% CI, 5.7–6.9%), of which 3.8% (95 CI, 3.2–4.4%) were Salmonella species and 2.5% (95% CI, 1.95-3%) were Shigella species. Unimproved water source (AOR = 5.08, 95% CI = 1.45, 17.25), open field (AOR = 2.3, 95% CI = 1.3, 5.03), rural residence (AOR = 1.8, 95% CI = 1.4, 7.5), Hand-washing practice (p = 0.001), and raw meat consumption (p = 0.002) were associated with occurrence of Salmonella and Shigella species. Salmonella and Shigella isolates were resistant to Ampicilin (100%). However, Salmonella isolates was sensitive to Norfloxacin (100%). About 22.2% and 16.7% of Salmonella and Shigella isolates were multi-drug resistant, respectively.

Conclusion
Prevalence of Salmonella and Shigella species were lower than most studies done in Ethiopia. Hand-washing habit, water source type, Open field waste disposal habit, raw meat consumption and rural residence were associated with Salmonellosis and shigellosis. All isolated Salmonella were sensitive to norfloxacin. The evidence from this study underscores the need for improved water, sanitation and hygiene (WASH) system and the imperative to implement drug susceptibility tests for the treatment of Salmonella and Shigella infection.
An adolescent case of ASXL3-related disorder with delayed onset of feeding difficulty
Authors: Arai Yuto , Okanishi Tohru , Okazaki Tetsuya , Awano Hiroyuki , Seyama Rie , Uchiyama Yuri , Matsumoto Naomichi , Tamasaki Akiko , Maegaki Yoshihiro 
Published: May 2024

Abstract
Background
ASXL3-related disorder, first described in 2013, is a genetic disorder with an autosomal dominant inheritance that is caused by a heterozygous loss-of-function variant in ASXL3. The most characteristic feature is neurodevelopmental delay with consistently limited speech. Feeding difficulty is a main symptom observed in infancy. However, no adolescent case has been reported.

Case presentation
A 14-year-old girl with ASXL3-related syndrome was referred to our hospital with subacute onset of emotional lability. Limbic encephalitis was ruled out by examination; however, the patient gradually showed a lack of interest in eating, with decreased diet volume. Consequently, she experienced significant weight loss. She experienced no symptoms of bulimia, or food allergy; therefore, avoidant/restrictive food intake disorder (ARFID) was clinically suspected.

Conclusions
We reported the first case of ASXL3-related disorder with adolescent onset of feeding difficulty. ARFID was considered a cause of the feeding difficulty.
Sleeping more than 8 h: a silent factor contributing to decreased muscle mass in Chinese community-dwelling older adults
Authors: Huang Qiongyu , Lin Hongsheng , Xiao Han , Zhang Liuwei , Chen Dafang , Dai Xiaotong 
Published: May 2024

Abstract
Background
Muscle mass loss is an age-related process that can be exacerbated by lifestyle, environmental and other factors, but can be mitigated by good sleep. The objective of this study was to investigate the correlation between varying time lags of sleep duration and the decline in muscle mass among individuals aged 60 years or older by using real-world health monitoring data obtained from wearable devices and smart home health monitoring devices.

Methods
This study included 86,037 observations from 2,869 participants in the Mobile Support System database. Missing data were supplemented by multiple imputation. The investigation utilized generalized estimating equations and restricted cubic spline curve to examine the relationship between sleep duration and low muscle mass. Various lag structures, including 0, 1, 2, 0–1, 0–2, and 1–2 months, were fitted, and the interaction effect of observation time with sleep duration was estimated for each lag structure. Additionally, subgroup analyses were conducted. The models were adjusted for various covariates, including gender, age, body mass index, footsteps, smoking status, drinking status, marital status, number of chronic diseases, number of medications, diabetes mellitus, hyperlipidemia, coronary artery disease, respiratory disease, and musculoskeletal disease and an interaction term between time and sleep duration.

Results
The results of the generalized estimating equation showed a significant correlation (p < 0.001) between sleep duration of 8 h or more and low muscle mass in older adults, using 6–7 h of sleep as a reference. This effect was seen over time and prolonged sleep accumulated over multiple months had a greater effect on muscle mass loss than a single month. The effect of long sleep duration on muscle mass loss was significantly greater in females than in males and greater in the over-75 than in the under-75 age group. Restricted cubic spline plots showed a non-linear relationship between sleep duration and low muscle mass (p < 0.001).

Conclusions
This study found an association between sustained nighttime sleep of more than eight hours and decreased muscle mass in older adults, especially older women.
Molecular interactions between metformin and D-limonene inhibit proliferation and promote apoptosis in breast and liver cancer cells
Authors: Salim Elsayed I. , Alabasy Mona M. , Nashar Eman M. El , Al-Zahrani Norah S. , Alzahrani Mohammed A. , Guo Zihu , Beltagy Doha M. , Shahen Mohamed 
Published: May 2024

Abstract
Background
Cancer is a fatal disease that severely affects humans. Designing new anticancer strategies and understanding the mechanism of action of anticancer agents is imperative.

Hypothesis/Purpose
In this study, we evaluated the utility of metformin and D-limonene, alone or in combination, as potential anticancer therapeutics using the human liver and breast cancer cell lines HepG2 and MCF-7.

Study design
An integrated systems pharmacology approach is presented for illustrating the molecular interactions between metformin and D-limonene.

Methods
We applied a systems-based analysis to introduce a drug–target–pathway network that clarifies different mechanisms of treatment. The combination treatment of metformin and D-limonene induced apoptosis in both cell lines compared with single drug treatments, as indicated by flow cytometric and gene expression analysis.

Results
The mRNA expression of Bax and P53 genes were significantly upregulated while Bcl-2, iNOS, and Cox-2 were significantly downregulated in all treatment groups compared with normal cells. The percentages of late apoptotic HepG2 and MCF-7 cells were higher in all treatment groups, particularly in the combination treatment group. Calculations for the combination index (CI) revealed a synergistic effect between both drugs for HepG2 cells (CI = 0.14) and MCF-7 cells (CI = 0.22).

Conclusion
Our data show that metformin, D-limonene, and their combinations exerted significant antitumor effects on the cancer cell lines by inducing apoptosis and modulating the expression of apoptotic genes.
Barriers to implementing problem-based learning at the school of medicine of Debre Berhan University, Ethiopia
Authors: Tefera Aklile Semu , Melaku Ermiyas Endewunet , Urgie Besufekad Mulugeta , Hassen Erzik Muhammed , Tamene Tilahun Deresse , Gebeyaw Enguday Demeke 
Published: May 2024

Abstract
Background
Implementing PBL in teaching and learning can be challenging due to a variety of complex barriers. Studies on barriers to the implementation of problem-based learning in Ethiopia are scarce. This study aimed to explore the barriers to the implementation of problem-based learning at the Debre Berhan University Medical School.

Methods
A qualitative study was conducted among faculty and medical students at the medical school. Purposive sampling was used to select participants. Semi-structured interviews were conducted with tutors and academic leaders, including the problem-based learning coordinator, the biomedical sciences coordinator, and the school dean. Data was also collected from students through focus group discussions. All interviews and discussions were recorded. The four steps of data analysis of Spradley, including domain analysis, taxonomic analysis, componential analysis, and theme analysis, were employed.

Results
The study identified student-related, tutor-related, case scenario-related, and assessment-related barriers as the most significant obstacles to implementing problem-based learning. These barriers included work overload for both students and tutors, lack of training and experience among tutors, student reluctance, absence of standardized case scenarios, subjectivity of assessment methods, and on-the-spot assessment of students.

Conclusions and recommendations
: Lack of both tutor and student commitment, lack of standardized cases, absence of a recognition of staff input, gap in communication skills, work overload, lack of continuous training, and at-spot evaluation of students were identified as the main barriers to the implementation of PBL.
A qualitative study of the value of simulation-based training for nursing students in primary care
Authors: Bray Lucy , Østergaard Doris 
Published: May 2024

Abstract
Background
Clinical placement is an essential component of nursing education, providing students with the opportunity to apply theoretical knowledge to practice. However, challenges such as lack of supervision and passive involvement in tasks can hinder the learning experience. Supplementing clinical placement with simulation-based training (SBT) has been explored as a potential solution, though this approach has been underexplored within primary care. This study aimed to explore the educational value of a supplemental SBT course for nursing students during primary care placement, as well as the adaption of this approach to a primary care setting.

Methods
A qualitative descriptive study was conducted at a medical education and simulation academy in Denmark. Sixth-semester nursing students on placement in primary care were invited to participate. The intervention consisted of a three-day simulation course covering core nursing competencies and common clinical conditions encountered within primary care. Simulation adopted a standardised patient approach. Data was collected using focus group interviews, which was analysed using inductive thematic analysis.

Results
Thirty-one nursing students participated in the study. Seven themes emerged from the analysis, including perceptions, educational value, simulation adjustments to primary care, educators’ competencies, learning needs within primary care, challenges of clinical placement and career guidance. Generally, participants perceived the intervention positively, appreciating its relevance to their clinical placement and its educational impact in this context. Participants also provided insights into the adaptation of SBT to a primary care setting, as well as nursing students’ learning needs within this context.

Conclusion
The findings indicate that the intervention had a positive impact on participant competencies within this context and enhanced their clinical practice within primary care. Furthermore, the results inform educators on how to effectively employ primary care-related SBT. Overall, this study supports the need for an increased application of SBT within primary care.

Trial registration
Not relevant.
Understanding exopolysaccharide byproduct formation in Komagataella phaffii fermentation processes for recombinant protein production
Authors: Steimann Thomas , Heite Zoe , Germer Andrea , Blank Lars Mathias , Büchs Jochen , Mann Marcel , Magnus Jørgen Barsett 
Published: May 2024

Abstract
Background
Komagataella phaffii (Pichia pastoris) has emerged as a common and robust biotechnological platform organism, to produce recombinant proteins and other bioproducts of commercial interest. Key advantage of K. phaffii is the secretion of recombinant proteins, coupled with a low host protein secretion. This facilitates downstream processing, resulting in high purity of the target protein. However, a significant but often overlooked aspect is the presence of an unknown polysaccharide impurity in the supernatant. Surprisingly, this impurity has received limited attention in the literature, and its presence and quantification are rarely addressed.

Results
This study aims to quantify this exopolysaccharide in high cell density recombinant protein production processes and identify its origin. In stirred tank fed-batch fermentations with a maximal cell dry weight of 155 g/L, the polysaccharide concentration in the supernatant can reach up to 8.7 g/L. This level is similar to the achievable target protein concentration. Importantly, the results demonstrate that exopolysaccharide production is independent of the substrate and the protein production process itself. Instead, it is directly correlated with biomass formation and proportional to cell dry weight. Cell lysis can confidently be ruled out as the source of this exopolysaccharide in the culture medium. Furthermore, the polysaccharide secretion can be linked to a mutation in the HOC1 gene, featured by all derivatives of strain NRRL Y-11430, leading to a characteristic thinner cell wall.

Conclusions
This research sheds light on a previously disregarded aspect of K. phaffii fermentations, emphasizing the importance of monitoring and addressing the exopolysaccharide impurity in biotechnological applications, independent of the recombinant protein produced.
A simple, field-applicable method to increase the infectivity of wild isolates of Plasmodium falciparum to mosquito vectors
Authors: Ouattara Seydou Bienvenu , Hien Domonbabele F. D. S. , Nao Ekôbié T. , Paré Prisca S. L. , Guissou Edwige , Cohuet Anna , Morlais Isabelle , Yerbanga Rakiswendé S. , Dabiré Kounbobr R. , Ouédraogo Jean Bosco , Mouline Karine , Lefèvre Thierry 
Published: May 2024

Abstract
Background
The direct membrane feeding assay (DMFA), whereby gametocyte-infected blood is collected from human donors and from which mosquitoes feed through a membrane, is proving essential for assessing parameters influencing Plasmodium transmission potential in endemic countries. The success of DMFAs is closely tied to gametocyte density in the blood, with relatively high gametocytaemia ensuring optimal infection levels in mosquitoes. As transmission intensity declines with control efforts, the occurrence of asymptomatic individuals with low gametocyte densities, who can significantly contribute to the infectious reservoir, is increasing. This poses a limitation to studies relying on the experimental infection of large numbers of mosquitoes with natural isolates of Plasmodium. A simple, field-applicable method is presented for improving parasite infectivity by concentrating Plasmodium falciparum gametocytes.

Methods
Anopheles gambiae received one of the following 5 blood treatments through DMFA: (i) whole blood (WB) samples from naturally-infected donors; (ii) donor blood whose plasma was replaced with the same volume of Plasmodium-naive AB + serum (1:1 control); (iii) plasma replaced with a volume of malaria-naïve AB + serum equivalent to half (1:1/2), or to a quarter (1:1/4), of the initial plasma volume; and (v) donor blood whose plasma was fully removed (RBC). The experiment was repeated 4 times using 4 distinct wild parasite isolates. Seven days post-infection, a total of 1,095 midguts were examined for oocyst presence.

Results
Substituting plasma with reduced amounts (1:1/2 and 1:1/4) of Plasmodium-naive AB + serum led to a 31% and 17% increase of the mosquito infection rate and to a 85% and 308% increase in infection intensity compared to the 1:1 control, respectively. The full removal of plasma (RBC) reduced the infection rate by 58% and the intensity by 64% compared to the 1:1 control. Reducing serum volumes (1:1/2; 1:1/4 and RBC) had no impact on mosquito feeding rate and survival when compared to the 1:1 control.

Conclusions
Concentrating gametocytic blood by replacing natural plasma by lower amount of naive serum can enhance the success of mosquito infection. In an area with low gametocyte density, this simple and practical method of parasite concentration can facilitate studies on human-to-mosquito transmission such as the evaluation of transmission-blocking interventions.
Time Kinetics and prognosis roles of calcitonin after surgery for medullary thyroid carcinoma
Authors: Guo Fengli , Fu Guiming , Li Fangxuan , Hua Yitong , Wang Zhongyu , Zheng Xiangqian , Zhao Jingzhu , Gao Ming 
Published: May 2024

Abstract
Background
Medullary thyroid carcinoma (MTC) is a malignant tumor with low incidence. Currently, most studies have focused on the prognostic risk factors of MTC, whatever, time kinetic and risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) are yet to be elucidated.

Methods
A retrospective study was conducted for 190 MTC patients. Risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) were analyzed. The predictors of calcitonin normalization time (CNT) and biochemical persistent/recurrent time (BPT) were identified. Further, the prognostic roles of CNT and BPT were also demonstrated.

Results
The 5- and 10-year DFS were 86.7% and 70.2%, respectively. The 5- and 10-year OS were 97.6% and 78.8%, respectively. CN was achieved in 120 (63.2%) patients, whereas BP was presented in 76 (40.0%) patients at the last follow up. After curative surgery, 39 (32.5%) and 106 (88.3%) patients achieved CN within 1 week and 1 month. All patients who failed to achieve CN turned to BP over time and 32/70 of them developed structural recurrence. The median time of CNT and BPT was 1 month (1 day to 84 months) and 6 month (3 day to 63months), respectively. LNR > 0.23 and male gender were independent predictors for CN and BP. LNR > 0.23 (Hazard ratio (HR), 0.24; 95% CI,0.13–0.46; P < 0.01) and male gender (HR, 0.65; 95% CI, 0.42–0.99; P = 0.045) were independent predictors for longer CNT. LNR > 0.23 (HR,5.10; 95% CI,2.15–12.11; P < 0.01) was still the strongest independent predictor followed by preoperative serum Ctn > 1400ng/L (HR,2.34; 95% CI,1.29–4.25; P = 0.005) for shorter BPT. In survival analysis, primary tumor size > 2 cm (HR, 5.81; 95% CI,2.20-15.38; P < 0.01), CNT > 1 month (HR, 5.69; 95% CI, 1.17–27.61; P = 0.031) and multifocality (HR, 3.10; 95% CI, 1.45–6.65; P = 0.004) were independent predictor of DFS.

Conclusion
Early changes of Ctn after curative surgery can predict the long-term risks of biochemical and structural recurrence, which provide a useful real-time prognostic information. LNR significantly affect the time kinetic of biochemical prognosis. Tumor burden and CNT play a crucial role in MTC survival, the intensity of follow-up must be tailored accordingly.
Novel genome-wide DNA methylation profiling reveals distinct epigenetic landscape, prognostic model and cellular composition of early-stage lung adenocarcinoma
Authors: Gan Junwen , Huang Meng , Wang Weishi , Fu Guining , Hu Mingyuan , Zhong Hongcheng , Ye Xin , Cao Qingdong 
Published: May 2024

Abstract
Background
Lung adenocarcinoma (LUAD) has been a leading cause of cancer-related mortality worldwide. Early intervention can significantly improve prognosis. DNA methylation could occur in the early stage of tumor. Comprehensive understanding the epigenetic landscape of early-stage LUAD is crucial in understanding tumorigenesis.

Methods
Enzymatic methyl sequencing (EM-seq) was performed on 23 tumors and paired normal tissue to reveal distinct epigenetic landscape, for compared with The Cancer Genome Atlas (TCGA) 450K methylation microarray data. Then, an integrative analysis was performed combined with TCGA LUAD RNA-seq data to identify significant differential methylated and expressed genes. Subsequently, the prognostic risk model was constructed and cellular composition was analyzed.

Results
Methylome analysis of EM-seq comparing tumor and normal tissues identified 25 million cytosine-phosphate-guanine (CpG) sites and 30,187 differentially methylated regions (DMR) with a greater number of untraditional types. EM-seq identified a significantly higher number of CpG sites and DMRs compared to the 450K microarray. By integrating the differentially methylated genes (DMGs) with LUAD-related differentially expressed genes (DEGs) from the TCGA database, we constructed prognostic model based on six differentially methylated-expressed genes (MEGs) and verified our prognostic model in GSE13213 and GSE42127 dataset. Finally, cell deconvolution based on the in-house EM-seq methylation profile was used to estimate cellular composition of early-stage LUAD.

Conclusions
This study firstly delves into novel pattern of epigenomic DNA methylation and provides a multidimensional analysis of the role of DNA methylation revealed by EM-seq in early-stage LUAD, providing distinctive insights into its potential epigenetic mechanisms.
From isolation to revival: trade recovery amid global health crises
Authors: Yang Lijuan 
Published: May 2024

Abstract
Background
The COVID-19 pandemic has highlighted the importance of designing effective trade recovery measures in response to global health events (GHEs). This study combines international trade risk management theory and multi-case comparative analysis of past GHEs to present a theoretical framework for designing national trade recovery measures for future events.

Results
The research finds that during GHEs, trade risks shift to fundamental uncertainty, requiring spatial–temporal-subject dimension recovery measures. The study suggests changing the focus of trade recovery policy design from emergency-oriented and single-dimension measures to reserve-oriented and enduring-effect measures of comprehensive dimensions at micro- and macroeconomic levels.

Conclusion
The study contributes to the debate on managing trade risks in times of crisis, where there is a need to develop effective trade recovery measures that account for the complexities of global trade and the unique challenges of GHEs. The findings provide practical guidance for trade officials and policymakers to design measures in response to GHEs to improve a country’s overall trade recovery.