bluuebunny/crossref_metadata_2025_split huggingface dataset:
Four novel mutations identified in the COL4A3, COL4A4 and COL4A5 genes in 10 families with Alport syndrome
Authors: Wang Duocai , Pan Meize , Li Hang , Li Minchun , Li Ping , Xiong Fu , Xiao Hongbo 
Published: July 2024

Abstract
Background
Alport syndrome (AS) is an inherited nephropathy caused by mutations in the type IV collagen genes. It is clinically characterized by damage to the eyes, ears and kidneys. Diagnosis of AS is hampered by its atypical clinical picture, particularly when the typical features, include persistent hematuria and microscopic changes in the glomerular basement membrane (GBM), are the only clinical manifestations in the patient.

Methods
We screened 10 families with suspected AS using whole exome sequencing (WES) and analyzed the harmfulness, conservation, and protein structure changes of mutated genes. In further, we performed in vitro functional analysis of two missense mutations in the COL4A5 gene (c.2359G > C, p.G787R and c.2605G > A, p.G869R).

Results
We identified 11 pathogenic variants in the type IV collagen genes (COL4A3, COL4A4 and COL4A5). These pathogenic variants include eight missense mutations, two nonsense mutations and one frameshift mutation. Notably, Family 2 had digenic mutations in the COL4A3 (p.G1170A) and UMOD genes (p.M229K). Family 3 had a digenic missense mutation (p.G997E) in COL4A3 and a frameshift mutation (p.P502L fs*151) in COL4A4. To our knowledge, four of the 11 mutations are novel mutations. In addition, we found that COL4A5 mutation relation mRNA levels were significantly decreased in HEK 293 T cell compared to control, while the cellular localization remained the same.

Conclusions
Our research expands the spectrum of COL4A3-5 pathogenic variants, which is helpful for clinical and scientific research.
A case of Ph+ acute lymphoblastic leukemia and EGFR mutant lung adenocarcinoma synchronous overlap: may one TKI drug solve two diseases?
Authors: Zhang Qi , Zhou Jing-dong , Ding Hao , Yang Lei , Lu Chao , Chu Ming-qiang , Qian Jun , Zhang Ting-juan 
Published: July 2024

Abstract
Background
Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) refers to ALL patients with t(9;22) cytogenetic abnormalities, accounting for about 25% of ALL. Lung adenocarcinoma (LUAD) is the most common pathological type of non-small-cell lung cancer, which has a frequency of approximately 45% cases with mutations in EGFR. Both Ph+ ALL and EGFR mutant LUAD are involved in the pathogenesis of the abnormal activation of the tyrosine kinase pathway. Although the second primary hematological malignancy after the treatment of solid tumors is common in clinics, the synchronous multiple primary malignant tumors of hematological malignancy overlap solid tumors are uncommon, even both tumors involved in the pathogenesis of the abnormal activation of the tyrosine kinase pathway are extremely rare.

Case presentation
An 84-year-old man with fatigue and dizziness was diagnosed with Ph+ ALL. Meanwhile, a chest CT indicated a space-occupying lesions, characterized by the presence of void, in the right lower lope with the enlargement of mediastinal lymph node and right pleural effusion. After a few weeks, the patient was diagnosed with LUAD with EGFR exon 19 mutation. Both tyrosine kinase inhibitors (TKI) (Flumatinib) and EGFR-TKI (Oxertinib) was used for the patients, and finally have controlled both diseases.

Conclusion
As far as we know, we for the first time reported a case of Ph+ ALL and EGFR mutant LUAD synchronous overlap, of which pathogenesis is related to abnormal tyrosine kinase activation. This patient was successfully treated with two different TKIs without serious adverse events.
Trends in direct health care costs among US adults with atherosclerotic cardiovascular disease with and without diabetes
Authors: Shah Chintal H. , Fonarow Gregg C. , Echouffo-Tcheugui Justin B. 
Published: July 2024

Abstract
Objective
Population-based national data on the trends in expenditures related to coexisting atherosclerotic cardiovascular diseases (ASCVD) and diabetes is scarce. We assessed the trends in direct health care expenditures for ASCVD among individuals with and without diabetes, which can help to better define the burden of the co-occurrence of diabetes and ASCVD.

Methods
We used 12-year data (2008–2019) from the US national Medical Expenditure Panel Survey including 28,144 U.S individuals aged ≥ 18 years. Using a two-part model (adjusting for demographics, comorbidities and time), we estimated mean and adjusted incremental medical expenditures by diabetes status among individuals with ASCVD. The costs were direct total health care expenditures (out-of-pocket payments and payments by private insurance, Medicaid, Medicare, and other sources) from various sources (office-based visits, hospital outpatient, emergency room, inpatient hospital, pharmacy, home health care, and other medical expenditures).

Results
The total direct expenditures for individuals with ASCVD increased continuously by 30% from $14,713 (95% confidence interval (CI): $13,808–$15,619) in 2008–2009 to $19,145 (95% CI: $17,988–$20,301) in 2008–2019. Individuals with diabetes had a 1.5-fold higher mean expenditure that those without diabetes. A key driver of the observed increase in direct costs was prescription drug costs, which increased by 37% among all individuals with ASCVD. The increase in prescription drug costs was more pronounced among individuals with ASCVD and diabetes, in whom a 45% increase in costs was observed, from $5184 (95% CI: $4721–$5646) in 2008–2009 to $7501 (95% CI: $6678–$8325) in 2018–2019. Individuals with ASCVD and diabetes had $5563 (95% CI: $4643–$6483) higher direct incremental expenditures compared with those without diabetes, after adjusting for demographics and comorbidities. Among US adults with ASCVD, the estimated adjusted total direct excess medical expenditures were $42 billion per year among those with diabetes vs. those without diabetes.

Conclusions
In the setting of ASCVD, diabetes is associated with significantly increased health care costs, an increase that was driven by marked increase in medication costs.
Fitness costs of Tn1546-type transposons harboring the vanA operon by plasmid type and structural diversity in Enterococcus faecium
Authors: Kim Dokyun , Kang Da Young , Choi Min Hyuk , Hong Jun Sung , Kim Hyun Soo , Kim Young Ree , Kim Young Ah , Uh Young , Shin Kyeong Seob , Shin Jeong Hwan , Kim Soo Hyun , Shin Jong Hee , Jeong Seok Hoon 
Published: July 2024

Abstract
Background
This study analyzed the genetic traits and fitness costs of vancomycin-resistant Enterococcus faecium (VREfm) blood isolates carrying Tn1546-type transposons harboring the vanA operon.

Methods
All E. faecium blood isolates were collected from eight general hospitals in South Korea during one-year study period. Antimicrobial susceptibility testing and vanA and vanB PCR were performed. Growth rates of E. faecium isolates were determined. The vanA-positive isolates were subjected to whole genome sequencing and conjugation experiments.

Results
Among 308 E. faecium isolates, 132 (42.9%) were positive for vanA. All Tn1546-type transposons harboring the vanA operon located on the plasmids, but on the chromosome in seven isolates. The plasmids harboring the vanA operon were grouped into four types; two types of circular, nonconjugative plasmids (Type A, n = 50; Type B, n = 46), and two types of putative linear, conjugative plasmids (Type C, n = 16; Type D, n = 5). Growth rates of vanA-positive E. faecium isolates were significantly lower than those of vanA-negative isolates (P < 0.001), and reduction in growth rate under vancomycin pressure was significantly larger in isolates harboring putative linear plasmids than in those harboring circular plasmids (P = 0.020).

Conclusions
The possession of vanA operon was costly to bacterial hosts in antimicrobial-free environment, which provide evidence for the importance of reducing vancomycin pressure for prevention of VREfm dissemination. Fitness burden to bacterial hosts was varied by type and size of the vanA operon-harboring plasmid.
Clinical data-based modeling of IVF live birth outcome and its application
Authors: Liu Liu , Liang Hua , Yang Jing , Shen Fujin , Chen Jiao , Ao Liangfei 
Published: July 2024

Abstract
Background
The low live birth rate and difficult decision-making of the in vitro fertilization (IVF) treatment regimen bring great trouble to patients and clinicians. Based on the retrospective clinical data of patients undergoing the IVF cycle, this study aims to establish classification models for predicting live birth outcome (LBO) with machine learning methods.

Methods
The historical data of a total of 1405 patients undergoing IVF cycle were first collected and then analyzed by univariate and multivariate analysis. The statistically significant factors were identified and taken as input to build the artificial neural network (ANN) model and supporting vector machine (SVM) model for predicting the LBO. By comparing the model performance, the one with better results was selected as the final prediction model and applied in real clinical applications.

Results
Univariate and multivariate analysis shows that 7 factors were closely related to the LBO (with P < 0.05): Age, ovarian sensitivity index (OSI), controlled ovarian stimulation (COS) treatment regimen, Gn starting dose, endometrial thickness on human chorionic gonadotrophin (HCG) day, Progesterone (P) value on HCG day, and embryo transfer strategy. By taking the 7 factors as input, the ANN-based and SVM-based LBO models were established, yielding good prediction performance. Compared with the ANN model, the SVM model performs much better and was selected as the final model for the LBO prediction. In real clinical applications, the proposed ANN-based LBO model can predict the LBO with good performance and recommend the embryo transfer strategy of potential good LBO.

Conclusions
The proposed model involving all essential IVF treatment factors can accurately predict LBO. It can provide objective and scientific assistance to clinicians for customizing the IVF treatment strategy like the embryo transfer strategy.
Physical activity, gut microbiota and the nexuses of metabolic and psychological disorders in children and adolescents
Authors: Ashaolu Joseph Opeolu , Sylvain Some Y. Marie , Otuechere Chiagoziem A. , Bamigboye Olufunke C. , Ashaolu Tolulope Joshua 
Published: July 2024

AbstractThe burden of health issues surrounding the children and adolescents (ChAds) population is of great concern. From metabolic disorders such as obesity, non-alcoholic fatty liver disease, diabetes, multiple sclerosis including mental and several other psychological disorders like attention deficit hyperactivity, internet addiction, autism spectrum, subthreshold mood symptoms and depression, and stress disorders, is a nexus of the gut microbiota (GM) profile and physical activity (PA), as they both play a crucial role in ameliorating these disorders. The aim of this review is to explore the disorders with regard to their association with ChAds’ GM and its health. We started with brief descriptions of PA and its connections with GM profile cum health in ChAds. In addition, the disorders in ChAds were broadly classified into metabolic and psychological. Observations from the discussed sections show that exercise and physical activity are efficient methods for enhancing physical, metabolic, and mental health, which are often GM-mediated, and thus might require certain levels of personalization. Furthermore, age, gender, genetics, baseline BMI, baseline exercise level, and diet are key parameters to be explored when proffering intervention of combative mechanisms against these disorders.
Impact of fish oil supplementation on plasma levels of highly unsaturated fatty acid-containing lipid classes and molecular species in American football athletes
Authors: Mullins Veronica Anne , Snider Justin M. , Michael Bryce , Porter Lydia Rose , Brinton Roberta Diaz , Chilton Floyd H. 
Published: July 2024

Abstract
Background
Previous studies have linked sports-related concussions and repeated subconcussive head impacts in contact sport athletes to elevated brain injury biomarkers. Docosahexaenoic acid (DHA), the primary omega-3 (n-3) highly unsaturated fatty acid (HUFA) in the brain, has shown neuroprotective effects in animal models after brain injury, but clinical research has shown mixed results.

Methods
We conducted a randomized, double-blind, placebo-controlled study on 29 Division 1 collegiate American football players, exploring the impact of DHA (2.5 g) and eicosapentaenoic acid (EPA) (1.0 g) supplied as ethyl esters, on levels of plasma lipids shown to cross the blood-brain barrier. Dietary intake data was collected using food frequency questionnaires (FFQ). Complex lipids and unesterified fatty acids were isolated from plasma, separated via reversed-phase liquid chromatography and analyzed by targeted lipidomics analysis.

Results
FFQ results indicated that participants had low dietary n-3 HUFA intake and high omega-6 (n-6):n-3 polyunsaturated fatty acids (PUFA) and HUFA ratios at baseline. After DHA + EPA supplementation, plasma lysophosphatidylcholine (LPC) containing DHA and EPA significantly increased at all timepoints (weeks 17, 21, and 26; p < 0.0001), surpassing placebo at Weeks 17 (p < 0.05) and 21 (p < 0.05). Phosphatidylcholine (PC) molecular species containing DHA or EPA, PC38:6 PC36:6, PC38:7, PC40:6, and PC40:8, increased significantly in the DHA + EPA treatment group at Weeks 17 (and 21. Plasma concentrations of non-esterified DHA and EPA rose post-supplementation in Weeks 17 and 21.

Conclusions
This study demonstrates that n-3 HUFA supplementation, in the form of ethyl esters, increased the DHA and EPA containing plasma lipid pools the have the capacity to enrich brain lipids and the potential to mitigate the effects of sports-related concussions and repeated subconcussive head impacts.

Trial Registration
All deidentified data are available at ClinicalTrials.gov #NCT0479207.
Application of 3D bioprinting technology apply to assessing Dangguiniantongtang (DGNT) decoctions in arthritis
Authors: Liang Zhichao , Han Yunxi , Chen Tao , Wang Jinwu , Lin Kaili , Yuan Luying , Li Xuefei , Xu Hao , Wang Tengteng , Liu Yang , Xiao Lianbo , Liang Qianqian 
Published: July 2024

AbstractThe aim of this study was to develop a three-dimensional (3D) cell model in order to evaluate the effectiveness of a traditional Chinese medicine decoction in the treatment of arthritis. Chondrocytes (ATDC5) and osteoblasts (MC3T3-E1) were 3D printed separately using methacryloyl gelatin (GelMA) hydrogel bioinks to mimic the natural 3D cell environment. Both cell types showed good biocompatibility in GelMA. Lipopolysaccharide (LPS) was added to the cell models to create inflammation models, which resulted in increased expression of inflammatory factors IL-1β, TNF-α, iNOS, and IL-6, and decreased expression of cell functional genes such as Collagen II (COLII), transcription factor SOX-9 (Sox9), Aggrecan, alkaline phosphatase (ALP), RUNX family transcription factor 2 (Runx2), Collagen I (COLI), Osteopontin (OPN), and bone morphogenetic protein-2 (BMP-2). The created inflammation model was then used to evaluate the effectiveness of Dangguiniantongtang (DGNT) decoctions. The results showed that DGNT reduced the expression of inflammatory factors and increased the expression of functional genes in the cell model. In summary, this study established a 3D cell model to assess the effectiveness of traditional Chinese medicine (TCM) decoctions, characterized the gene expression profile of the inflammatory state model, and provided a practical reference for future research on TCM efficacy evaluation for arthritis treatment.
Epigallocatechin gallate and curcumin inhibit Bcl-2: a pharmacophore and docking based approach against cancer
Authors: Bahadar Noor , Bahadar Sher , Sajid Abdul , Wahid Muqeet , Ali Ghadir , Alghamdi Abdullah , Zada Hakeem , Khan Tamreez , Ullah Shafqat , Sun Qingjia 
Published: July 2024

AbstractThe protein Bcl-2, well-known for its anti-apoptotic properties, has been implicated in cancer pathogenesis. Identifying the primary gene responsible for promoting improved cell survival and development has provided compelling evidence for preventing cellular death in the progression of malignancies. Numerous research studies have provided evidence that the abundance of Bcl-2 is higher in malignant cells, suggesting that suppressing Bcl-2 expression could be a viable therapeutic approach for cancer treatment. In this study, we acquired a compound collection using a database that includes constituents from Traditional Chinese Medicine (TCM). Initially, we established a pharmacophore model and utilized it to search the TCM database for potential compounds. Compounds with a fitness score exceeding 0.75 were selected for further analysis. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis identified six compounds with favorable therapeutic characteristics. The compounds that successfully passed the initial screening process based on the pharmacodynamic model were subjected to further evaluation. Extra-precision (XP) docking was employed to identify the compounds with the most favorable XP docking scores. Further analysis using the Molecular Mechanics Generalized Born Surface Area (MM-GBSA) method to calculate the overall free binding energy. The binding energy between the prospective ligand molecule and the target protein Bcl-2 was assessed by a 100 ns molecular dynamics simulation for curcumin and Epigallocatechin gallate (EGCG). The findings of this investigation demonstrate the identification of a molecular structure that effectively inhibits the functionality of the Bcl-2 when bound to the ligand EGCG. Consequently, this finding presents a novel avenue for the development of pharmaceuticals capable of effectively addressing both inflammatory and tumorous conditions.
Survival, mortality and epidemic risk status of COVID-19: a population-based Study in Golestan province, Iran
Authors: Kashiri Fatemeh , Sarbakhsh Parvin , Mohammadpoorasl Asghar , Seyedghasemi Navisa Sadat , Bagheri Ali , Akbari Hossein 
Published: July 2024

Abstract
Background
Appreciating the various dimensions of the coronavirus disease 2019 (COVID-19) pandemic can improve health systems and prepare them to deal better with future pandemics and public health events. This study was conducted to investigate the association between the survival of hospitalized patients with COVID-19 and the epidemic risk stratification of the disease in Golestan province, Iran.

Methods
In this study, all patients with COVID-19 who were hospitalized in the hospitals of Golestan province of Iran from February 20, 2020, to December 19, 2022, and were registered in the Medical Care Monitoring Center (MCMC) system (85,885 individuals) were examined.The community's epidemic risk status (ERS) was determined based on the daily incidence statistics of COVID-19. The survival distribution and compare Survival in different subgroups was investigated using Kaplan–Meier and log-rank test and association between the survival and ERS by multiple Cox regression modeling.

Results
Out of 68,983 individuals whose data were correctly recorded, the mean age was 49 (SD = 23.98) years, and 52.8% were women. In total, 11.1% eventually died. The length of hospital stay was varying significantly with age, gender, ERS, underlying diseases, and COVID-19 severity (P < 0.001 for all). The adjusted hazard ratio of death for the ERS at medium, high, and very high-risk status compared to the low-risk status increased by 19%, 26%, and 56%, respectively (P < 0.001 for all).

Conclusions
Enhancing preparedness, facilitating rapid rises in hospital capacities, and developing backup healthcare capacities can prevent excessive hospital referrals during health crises and further deaths.
The predictive role of resilience and the ethical climate of hospital in the fatigue of surgical technologists working in operating rooms
Authors: Rambod Masoume , Pasyar Nilofar , Soltanian Marzieh 
Published: July 2024

AbstractBackgroundFatigue in surgical technologists is of paramount importance and is known as a priority because it can be regarded as a threat to the nurse’s health and patient’s safety. The fatigue level of healthcare workers can be affected by some factors, while the role of part of these factors is less known. This study aimed to determine the predictive role of resilience and the hospital ethical climate in the fatigue of surgical technologists working in operating rooms (ORs).MethodsThis is a cross-sectional study conducted on 217 surgical technologists working in ORs of hospitals affiliated with Shiraz University of Medical Sciences. Data were collected using Connor-Davidson’s Resilience scale, Olson’s Hospital Ethical Climate Survey, and the Multidimensional Fatigue Inventory, and then analyzed using Pearson’s correlation coefficient and multiple regression analysis.Results87.1% and 12.9% of surgical technologists reported low and high fatigue, respectively. All fatigue subscales had significant and negative relationships with resilience (p < 0.05). Moreover, the relationship between fatigue and ethical climate was significant (p = 0.02). The multiple linear regression model showed the predictive role of resilience in fatigue (β=-0.29,P < 0.001). According to the model, 10% of the change of fatigue was related to resilience and ethical climate.ConclusionThe present study demonstrated the relationship between resilience and ethical climate with fatigue. Moreover, resilience was a predictor of the surgical technologists’ fatigue, so that their fatigue decreased with increasing resilience. However, future studies are recommended to determine other factors influencing fatigue in surgical technologists.
Minimum acceptable diet and associated factors among 6–23 months old children enrolled in outpatient therapeutic program in the Tulla district, Sidama region, Ethiopia: a community-based cross-sectional study
Authors: Markos Mesfin , Samuel Beniyam , Challa Alemzewed 
Published: July 2024

Abstract
Background
Improving the minimum acceptable diet (MAD) is essential for ensuring optimal growth and development of children, as well as preventing malnutrition and its consequences. Previous studies in Ethiopia have focused on the magnitude and determinants of a minimum acceptable diet. However, much emphasis was not given to minimum acceptable diet and its associated factors among 6–23 months old children enrolled in Outpatient therapeutic programs (OTP), particularly, in the study area. This study determines the minimum acceptable diet and associated factors among 6–23-month-old children enrolled in OTP.

Methods
A community-based cross-sectional study was conducted among 346 randomly selected mothers with children aged 6–23 months who were admitted to the OTP. The data were collected using interviewer-administered structured questionnaires. The data were entered, cleaned, coded into Epidata version 4.6, and exported to SPSS version 26 for further analysis. Multivariate logistic regression was used to assess the determinants of MAD.

Results
The overall prevalence of minimum Acceptable diet among children aged 6–23 months enrolled to OTP was 14.5% (95% CI: 12.02-19%). The odds of MAD were 1.9 times higher among children aged 18–23 months compared to children aged 6–11 months (AOR = 1.9, 95% CI ((1.2 3.9). The odds of MAD were 2.9times higher in children whose mothers had a good knowledge on recommended feeding (AOR = 2.9, 95% CI (1.2, 6.35). Mothers who had no formal education were 81% less likely to provide minimum acceptable diets for their children compared to their counterpart.(AOR = 1.94, 95% CI = 1.24, 4.19).

Conclusion
The practice of a minimum acceptable diet is inadequate. Nutrition education should be emphasized to improve the mothers’ nutrition knowledge regarding infant and young child feeding recommendations, to support mothers in overcoming barriers to feeding their children with adequate diets, and to foster complementary feeding practices for malnourished children.