bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of waterborne diseases: A case study of Khyber Pakhtunkhwa, Pakistan
Authors: Atif Muhammad , Ayub Gohar , Shakoor Fazal , Farooq Muhammad , Iqbal Muhammad , Zaman Qamruz , Ilyas Muhammad 
Published: July 2024

Objectives: In Pakistan, the degradation of drinking water quality is exacerbated by the increasing population size and rapid industrialization. Contaminated water serves as the predominant source of numerous diseases, including diarrhea, gastroenteritis, and typhoid. This article explores the evolution of waterborne diseases across 21 districts of the Khyber Pakhtunkhwa province in Pakistan by monitoring changes in the clustering solutions. Methods: The data employed in this study were sourced from 21 districts of KP by the Director-General Health Services. Cluster analysis was utilized to uncover patterns in waterborne disease incidence, while principal component analysis was employed to reveal underlying patterns and reduce dimensionality. Additionally, the MONItoring Clusters (MONIC) framework was applied for change detection, facilitating the identification of significant shifts in disease patterns over time and aiding in the understanding of temporal dynamics. Results: Our analysis indicates that two clusters survived consistently over time, while other clusters exhibited inconsistency. Profiling of the surviving clusters (C12 → C24 → C32 → C43) suggests a gradual increase in cases of bloody diarrhea in the Swat Valley, Hangu, Karak, and Lakki Marwat regions. Similarly, profiling of the surviving clusters (⊙→ C22 → C34 → C44) suggests an increase in the acute watery diarrhea (non-cholera) and typhoid fever in the regions of Peshawar, Nowshera, and Swabi. Conclusion: The findings of this study hold significant importance as they pinpoint the most vulnerable regions for various waterborne diseases. These insights offer valuable guidance to policymakers and health officials, empowering them to implement effective measures for controlling waterborne diseases in the respective regions of Khyber Pakhtunkhwa, Pakistan.
“I was afraid to go to the hospital”: A qualitative analysis and ethical implications of the impacts of COVID-19 on the health and medical care of older adults in Ethiopia
Authors: Mussie Kirubel Manyazewal , Setchell Jenny , Kaba Mirgissa , Elger Bernice Simone 
Published: July 2024

Objective: The COVID-19 pandemic has brought severe health consequences among older adults and posed ethical challenges. The aim of this study was to explore the impacts of COVID-19 on the health and medical care of older adults in Ethiopia and associated ethical implications, regardless of older adults’ COVID-19 infection status. Methods: In this qualitative study, we followed an inductive exploratory approach based on reflexive thematic analysis. We conducted semistructured interviews between March 2021 and November 2021 with 20 older adults and 26 health professionals who were selected from healthcare facilities and communities in Ethiopia using purposive and snowball sampling techniques. We audio-recorded, transcribed, translated, and inductively analyzed the interviews using thematic analysis. Results: Participants reported that the pandemic compromised the accessibility and quality of both COVID and non-COVID healthcare services for older adults, which negatively impacted older adults’ health conditions and medical care. Moreover, participants elaborated on the health conditions and care of older patients with COVID-19 and highlighted that older COVID-19 patients often have severe health conditions, do not get adequate COVID-19 care, and may receive lower priority for admission to intensive care units compared to younger patients when resources are limited. Conclusions: Results of this study showed that practices of COVID-19 care and measures may have led to adverse consequences such as limited availability and access to aged care in Ethiopia, which could have further health consequences on older patients. Our results contribute to a better understanding of ethical issues such as distributive justice and prioritization arising in the healthcare of older patients in times of global pandemic. It is imperative for local and international health policymakers and ethicists to further analyze and address the challenges that compromise the accessibility and continuity of quality care for older persons during a public healthcare crisis.
Access to essential medicines used in the management of noncommunicable diseases in Southern Ethiopia: Analysis using WHO/HAI methodology
Authors: Asmamaw Getahun , Shimelis Tekalign , Tewuhibo Dinksew , Bitew Teshome , Ayenew Wondim 
Published: July 2024

Objectives: This study aims to assess access to essential medicines used in the management of noncommunicable diseases through analysis of the availability, prices, and affordability of these essential medicines in Arba Minch town, Gamo Zone, Southern Ethiopia. Methods: A cross-sectional design was carried out using the World Health Organization/health action international methodology between 2 March and 2 May 2023, within public and private healthcare facilities located in Arba Minch town, Southern Ethiopia. The median price ratio served as a metric. Statistical tests like the Shapiro-Wilk and Kolmogorov-Smirnov were utilized to assess the normal distribution of price data. The Wilcoxon-Mann-Whitney U test was also employed to compare median buyer’s prices (patient prices) between public and private healthcare institutions. Treatment affordability was determined by estimating the number of days’ wages required by the lowest-paid government employee in Ethiopia to afford the prescribed medication regimen. Results: Among 23 health facilities surveyed, the pooled availability of essential medicine used in the management of noncommunicable diseases was 18.7% (range: 0%–30.1%), with the public and private facilities contributing 16.3% and 38.3%, respectively. The overall percentage of availability originator brand versions was 1.1% for overall health sectors, 0.6% for public sectors, and 1.2% for private sectors. The overall percent availability of lowest price generics was 36.2% (range: 0%–26.2%; public: 32.0%; private: 37.1%). Only seven lowest price generics satisfied the World Health Organization target of 80% and above. The overall median price of lowest price generic medicines in private was two times higher than in public sectors. The top five median price scorers were amlodipine, furosemide, insulin, beclomethasone, and salbutamol. The Mann-Whitney U test showed that 11.6% of lowest price generics medicines had a statistically significant median price disparity between the public and private sectors ( p < 0.05). The overall percent of unaffordability was found to be 100.0%, (public: 70.4; private: 100.0%). Conclusions: This study revealed the limited availability and potential financial burdens on patients seeking essential noncommunicable disease medications. Limited availability suggests the need for better supply chain management and consistent stock availability. The price disparities and affordability challenges identified underscore the necessity for policy interventions such as price regulation and subsidized programs to ensure equitable access to essential noncommunicable disease medications in Arba Minch town, Southern Ethiopia.
In-hospital mortality and associated factors among patients admitted with venous thromboembolism at selected public hospitals of Harar Town, Eastern Ethiopia
Authors: Abraham Dawit , Mishore Kirubel Minsamo , Nigussie Shambel , Jambo Abera , Gashaw Tigist 
Published: July 2024

Background: Venous thromboembolism is the third most common cause of cardiovascular death and is responsible for more than 3 million deaths annually worldwide. Despite high rates of morbidity and mortality associated with venous thromboembolism, limited studies have been conducted on in-hospital mortality and its associated factors in Ethiopia, particularly in study settings. Objective: To assess in-hospital mortality and associated factors among patients admitted with venous thromboembolism at selected public hospitals of Harar town, Eastern Ethiopia, from 10 March 2018 to 8 March 2022. Methods: A retrospective cohort study design was conducted among 502 patients admitted with venous thromboembolism at Hiwot Fana Comprehensive Specialized Hospital and Jugal General Hospital using a simple random sampling technique. Data extraction formats were used to collect data from patient medical record cards. Then data were coded and entered into EpiData version 3.1 computer programs and exported to SPSS version 26 for analysis. Bivariate and multivariate backward Cox regression analysis was used to verify the associated factors of in-hospital mortality among venous thromboembolism patients. A p-value of less than 0.05 at a 95% confidence interval was used to establish a statistically significant association. Results: A total of 502 patient medical record cards with outcome variables were included in the study. More than half of the patients 350 (69.7%) were females. Among the 502 patients who were admitted with venous thromboembolism, 8.2% (95% CI: 5.6–10.6) of patients had in-hospital mortality. DM (AHR = 4.28, 95% CI: 1.80–10.15, p = 0.001) and unfractionated heparin duration (AHR = 10.26, 95% CI: 2.45–43.01, p = 0.001) were statistically significant association with venous thromboembolism mortality. Conclusion: Approximately 8.2% of venous thromboembolism patients died in the hospital. Diabetes and heparin were independently associated with higher mortality. Therefore, it is better to give more attention to the patients co-morbid with diabetes mellitus and for unfractionated heparin treatment duration to reduce venous thromboembolism mortality.
Comparison of Clinical Outcomes After Medial Patellofemoral Ligament Reconstruction With Allograft Versus Autograft: A Matched-Cohort Analysis
Authors: Henstenburg Jeffrey , Pezzulo Joshua D. , Farronato Dominic M. , Johnson Emma B. , Bodnar John , Petrucelli Philip , Dodson Christopher , Freedman Kevin B. , Cohen Steven B. , Hammoud Sommer 
Published: July 2024

Background: Disruption of the medial patellofemoral ligament (MPFL) may lead to recurrent lateral patellar dislocation and patellofemoral chondral injury. Despite significant previous work investigating numerous performance parameters, the optimal graft choice for MPFL reconstruction for patellar instability remains unclear. Purpose: To compare functional outcomes scores, subjective recurrent instability, and revision rates between autograft and allograft in MPFL reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent MPFL reconstruction with autograft between 2013 and 2018 were identified. A 2:1 comparison group of patients who underwent MPFL reconstruction with allograft was matched by sex, age (±3 years), and body mass index (BMI) (±3 kg/m2). Patient characteristics, preoperative radiograph measurements, and intraoperative data were compared between the groups, as were patient-reported outcome measures, including International Knee Documentation Committee (IKDC) score, Lysholm score, Single Assessment Numerical Evaluation (SANE), and visual analog scale (VAS) for pain. Subjective recurrent instability and revision rate were also compared between groups. Results: The autograft group was composed of 30 patients (13 male, 17 female) with a mean age of 24.4 years and mean BMI of 25.0 kg/m2, and the allograft group was composed of 60 matched patients (25 male, 35 female) with a mean age of 24.1 years and mean BMI of 25.1 kg/m2. The autograft and allograft groups reported similar IKDC scores (73.0 vs 73.7; P = .678), Lysholm scores (77.5 vs 80.7; P = .514), SANE (72.0 vs 75.8; P = .236), and VAS pain (30.7 vs 26.6; P = .482), as well as similar rates of postoperative patellar subluxations (20.0% vs 19.3%; P = .867) and dislocations (10.0% vs 15.0%; P = .805). Conclusion: Both allograft and autograft were found to be viable options for MPFL reconstruction. There were no significant group differences in failure rates, patient-reported outcomes, pain, or complications between autograft and allograft MPFL reconstruction in this series.
Stroke-heart syndrome: Incidence and clinical outcomes of cardiac complications following intracerebral haemorrhage
Authors: Hoad Katie L , Jones Helen , Miller Gemma , Abdul-Rahim Azmil H , Lip Gregory YH , Buckley Benjamin JR 
Published: July 2024

Introduction: Newly diagnosed cardiovascular complications following an ischaemic stroke, termed stroke-heart syndrome, are common and associated with worse outcomes. Little is known regarding stroke-heart syndrome in relation to intracerebral haemorrhage (ICH). This study aimed to investigate the incidence and 5-year major adverse cardiovascular events (MACE; acute myocardial infarction, ischaemic stroke, all-cause mortality and recurrent ICH) of newly diagnosed cardiovascular complications following incident ICH, using a global federated database. Patients and methods: A retrospective cohort study was conducted using anonymised electronic medical records. Patients aged ⩾ 18 years with non-traumatic ICH and 5-year follow-up were included. Patients with newly diagnosed cardiovascular complications within 4-weeks following the initial ICH were 1:1 propensity score-matched with patients without new-onset cardiovascular complications. Each cardiovascular complications were investigated as a composite stroke-heart syndrome cohort and separately for associated MACE. Cox hazard regression models were used to determine 5-year incidence of MACE. Results: Before propensity score matching, 171,489 patients with non-traumatic ICH, 15% ( n = 26,449) experienced ⩾1 newly diagnosed cardiovascular complication within 4 weeks. After matching, patients with ICH and cardiovascular complications were associated with a significantly higher risk of 5-year MACE (HR 1.35 [95% CI 1.32–1.38]), and in each composite compared to matched controls. There was no significant risk of rehospitalisation over 5-year follow-up [HR 0.90 [0.73–1.13]). The risk of MACE was significantly higher in patients with newly diagnosed cardiovascular complications. Discussion and conclusions: Newly diagnosed cardiovascular complications following ICH (i.e. stroke-heart syndrome) were common and associated with a significantly worsened 5-year prognosis.
Inhibition of insulin degrading enzyme suppresses osteoclast hyperactivity via enhancing Nrf2-dependent antioxidant response in glucocorticoid-induced osteonecrosis of the femoral head
Authors: Yuan Tao , Wang Haojue , Wang Yi , Dong Shankun , Ge Jianxun , Li Ziqing , Sun Shui 
Published: July 2024

Abstract
Background
Osteoclast hyperactivation due to the pathological overproduction of reactive oxygen species (ROS) stimulated by glucocorticoids (GCs) is one of the key drivers behind glucocorticoid-induced osteonecrosis of the femoral head (GIONFH). The insulin degrading enzyme (IDE), a conserved Zn2+ metallo-endopeptidase, facilitates the DNA binding of glucocorticoid receptor and plays a substantial role in steroid hormone-related signaling pathways. However, the potential role of IDE in the pathogenesis of GIONFH is yet undefined.

Methods
In this study, we employed network pharmacology and bioinformatics analysis to explore the impact of IDE inhibition on GIONFH with 6bK as an inhibitory agent. Further evidence was collected through in vitro osteoclastogenesis experiments and in vivo evaluations involving methylprednisolone (MPS)-induced GIONFH mouse model.

Results
Enrichment analysis indicated a potential role of 6bK in redox regulation amid GIONFH development. In vitro findings revealed that 6bK could attenuate GCs-stimulated overactivation of osteoclast differentiation by interfering with the transcription and expression of key osteoclastic genes (Traf6, Nfatc1, and Ctsk). The use of an H2DCFDA probe and subsequent WB assays introduced the inhibitory effects of 6bK on osteoclastogenesis, linked with the activation of the nuclear factor erythroid-derived 2-like 2 (Nrf2)-mediated antioxidant system. Furthermore, Micro-CT scans validated that 6bK could alleviate GIONFH in MPS-induced mouse models.

Conclusions
Our findings suggest that 6bK suppresses osteoclast hyperactivity in GCs-rich environment. This is achieved by reducing the accumulation of intracellular ROS via promoting the Nrf2-mediated antioxidant system, thus implying that IDE could be a promising therapeutic target for GIONFH.
OsABA3 is Crucial for Plant Survival and Resistance to Multiple Stresses in Rice
Authors: Ni Haoling , Wu Wenshi , Yan Yanmin , Fang Yiyuan , Wang Changjian , Chen Jiayi , Chen Shali , Wang Kaini , Xu Chunjue , Tang Xiaoyan , Wu Jianxin 
Published: July 2024

AbstractPreharvest sprouting (PHS) is a serious problem in rice production as it leads to reductions in grain yield and quality. However, the underlying mechanism of PHS in rice remains unclear. In this study, we identified and characterized a preharvest sprouting and seedling lethal (phssl) mutant. The heterozygous phssl/+ mutant exhibited normal plant development, but severe PHS in paddy fields. However, the homozygous phssl mutant was seedling lethal. Gene cloning and genetic analysis revealed that a point mutation in OsABA3 was responsible for the mutant phenotypes. OsABA3 encodes a molybdenum cofactor (Moco) sulfurase. The activities of the sulfureted Moco-dependent enzymes such as aldehyde oxidase (AO) and xanthine dehydrogenase (XDH) were barely detectable in the phssl mutant. As the final step of abscisic acid (ABA) de novo biosynthesis is catalyzed by AO, it indicated that ABA biosynthesis was interrupted in the phssl mutant. Exogenous application of ABA almost recovered seed dormancy of the phssl mutant. The knock-out (ko) mutants of OsABA3 generated by CRISPR-Cas9 assay, were also seedling lethal, and the heterozygous mutants were similar to the phssl/+ mutant showing reduced seed dormancy and severe PHS in paddy fields. In contrast, the OsABA3 overexpressing (OE) plants displayed a significant increase in seed dormancy and enhanced plant resistance to PHS. The AO and XDH activities were abolished in the ko mutants, whereas they were increased in the OE plants. Notably, the Moco-dependent enzymes including nitrate reductase (NR) and sulfite oxidase (SO) showed reduced activities in the OE plants. Moreover, the OE plants exhibited enhanced resistances to osmotic stress and bacterial blight, and flowered earlier without any reduction in grain yield. Taken together, this study uncovered the crucial functions of OsABA3 in Moco sulfuration, plant development, and stress resistance, and suggested that OsABA3 is a promising target gene for rice breeding.
Sarcopenic obesity and pre-sarcopenia contribute to frailty in community-dwelling Italian older people: data from the FRASNET study
Authors: Damanti Sarah , Citterio Lorena , Zagato Laura , Brioni Elena , Magnaghi Cristiano , Simonini Marco , De Lorenzo Rebecca , Ruggiero Mariapia , Santoro Simona , Senini Eleonora , Messina Marco , Vitali Giordano , Manunta Paolo , Manfredi Angelo A. , Lanzani Chiara , Querini Patrizia Rovere 
Published: July 2024

Abstract
Background
The ageing process is characterized by a change of body composition with an increase of fat mass and a reduction of muscle mass. Above a certain threshold these alterations configure a condition named sarcopenic obesity (SO). SO is associated with physical frailty in Asian and Brazilian populations. SO impacts on physical frailty in other ethnic groups but its influence on general frailty which is multidimensional and includes cognitive, social and physical factors, remain insufficiently explored in the Italian population.

Methods
Frailty was measured in community dwelling Italian older adults enrolled in the FRASNET study with the frailty index (FI). The FI quantifies frailty as the ratio of the number of present health deficits to the total number of health deficits considered. Regression analyses were performed to assess the association between body composition categories and frailty. Classification and regression tree models were run to evaluate the frailty predictors.

Results
One Thousand One Hundred Fourteen participants of the FRASNET study were included in the present analysis. The sample was composed for the 60.5% by females and its median age was 72 years. The median FI score was 0.11 (IQR 0.07–0.20); 234 individuals (21%) were frail (FI ≥ 0.25). SO (B 0.074, 95% C.I. 0.05–0.1, p < 0.001) and pre-sarcopenia (without obesity B 0.03, 95% C.I, 0.007–0.044, p < 0.001, with obesity B 0.11, 95% C.I. 0.05–0.16, p < 0.001) were associated with frailty. Fat mass percentage predicted frailty in people aged 65–70 years whereas, muscle strength predicted general frailty in people aged 70–81 years.

Conclusion
Pre-sarcopenia and SO represent potentially treatable predictors of frailty.
The effect of exercise referral schemes and self-management strategies on use of prescription analgesics among community-dwelling older adults: registry linkage with randomised controlled trials
Authors: Svensson Nanna Herning , Thorlund Jonas Bloch , Olsen Pia Øllgaard , Søndergaard Jens , Wehberg Sonja , Andersen Helene Støttrup , Caserotti Paolo , Thilsing Trine 
Published: July 2024

Abstract
Background and objective
Exercise referral schemes and self-management strategies have shown positive effects on patient-reported and objectively measured outcomes, such as increased functional capacity and physical activity level. However, the impact of these interventions on analgesic use remains uncertain. We hypothesised that exercise referral schemes, either utilised alone or in combination with self-management strategies, is more effective in reducing use of prescription analgesics compared with a self-management strategy only.

Subjects and methods
We utilised data from two completed randomised controlled trials, namely The Welfare Innovation in Primary Prevention (n = 121) and The SITLESS project (n = 338), and information from the national Danish health registries, including the National Prescription Registry. The two trials have investigated the effectiveness of interventions, which include exercise referral schemes and self-management strategies, on various aspects such as physical function and levels of physical activity among community-dwelling older adults. The studies were conducted in the period 2015–2020 and comprised older adults aged 65+ years, living in three different Danish municipalities. Participants were recruited through nationally regulated preventive home-visits. To estimate changes in use of prescription analgesics over time, a linear fixed effects regression model was applied. The outcome measure was the mean total yearly defined daily dose of analgesics.

Results
All intervention groups showed a within-group increase in overall analgesic use, though not statistically significantly different from zero. There were no differences in estimated changes in mean total yearly defined daily dose when comparing the intervention groups to the group receiving the least extensive intervention (self-management strategies/control). The findings indicated that exercise referral schemes and self-management strategies, whether administrated individually or in combination, did not result in a reduction in analgesic use over time.