bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autosomal dominant macular dystrophy associated with THRB: identification of new families and variants
Authors: Fernández-Caballero Lidia , Blanco-Kelly Fiona , Swafiri Saoud Tahsin , Martín-Mérida María Inmaculada , Quinodoz Mathieu , Ullah Mukhtar , Carreño Ester , Martin-Gutierrez María Pilar , García-Sandoval Blanca , Minguez Pablo , Rivolta Carlo , Corton Marta , Ayuso Carmen 
Published: December 2024

Abstract

THRBencodes thyroid hormone receptor β which produces two human isoforms (TRβ1 and TRβ2) by alternative splicing. The first THRB variant associated with autosomal dominant macular dystrophy (ADMD), NM_001354712.2:c.283+1G>A, was recently described. This study aims to refine the ophthalmologic phenotype, report a novel THRB variant, and investigate the impact of these splicing variants at the protein level.
THRBvariants were identified by re-analysis of next-generation sequencing data from the FJD database. Family segregation was performed using Sanger sequencing. Clinical data were collected from self-reported ophthalmic history questionnaires and ophthalmic exams. Functional splicing test was performed by in vitrominigene approach.
We identified 12 patients with ADMD from 3 families carrying variants in THRB. Two families carried the variant NM_001354712.2:c.283+1G>A, and one the novel variant NM_001354712.2:c.283G>A. Patients exhibited common ophthalmologic findings with disruption of subfoveal ellipsoid layers, and variable onset of symptoms. Splicing assays showed complete exon 5 skipping or a 6 bp deletion in both variants.
Our results support the association of THRBwith ADMD. The high intra-familial variability could be influenced by phenotype modifiers. Aberrant TRβ1/TRβ2 proteins could lead to a gain-of-function mechanism. Including THRB in inherited retinal dystrophy genetic panels could enhance diagnoses and clinical patient management.
From Research to Practice: Bridging the Implementation Gap of Tranexamic Acid use in Total Knee Arthroplasty
Authors: Pfister Robin M , Pfister Benji F , Hager Ronald Lee , Sandholtz Nathan , Abulafia Daniel , Bradshaw David 
Published: December 2024

Abstract

Background:
The use of intravenous tranexamic acid (TXA), an antifibrinolytic agent, has been shown to effectively reduce total blood loss and transfusion rates in Total Knee Arthroplasty (TKA). The aim of this paper is to evaluate the implementation lag and clinical uptake of the use of TXA for primary TKA after publication of two landmark studies. Additionally, it assessed the efficacy of TXA use in TKA in reducing post operative blood transfusions and hospital length of stay (LOS).
Methods:
A total of 763 patients aged over 18 years of age underwent primary TKA at a level 4 metropolitan hospital in Australia between January 2011 and December 2017. Primary outcome measure was use of TXA at operative induction. Secondary outcome measures were post-operative blood transfusion, haemoglobin levels and in-hospital length of stay.
Results:
The rate of TXA uptake was ≥ 50% by April-June 2013, 1.5 years following landmark paper publication. TXA use was ≥90% by April-June 2015, equating to 3.5 years after landmark publication. For each additional year since publication, the odds that TXA was used in a TKA surgery increased by 254.3%, 95% CI (confidence interval) [195.2%, 334.1%].
There was a negative association between TXA use and blood transfusion rate (p < 0.001), while controlling for other variables. TXA use reduced the odds of blood transfusions occurring by 73.5%, 95% CI [35.8% and 89.8%]. Analysis showed that reduced LOS was seen even after controlling for post-operative blood transfusion (p<0.05).
Conclusion:
The implementation lag from research to clinical practice, using ≥90% TXA use in TKA as a proxy, was 3.5 years. The use of TXA reduced LOS and blood transfusion rate in TKA patients.
Obsessive-compulsive disorder due to temporal lobe porencephaly: a case report
Authors: Deng Gaoju , Cao Yuan , Qiu Changjian 
Published: December 2024

Abstract

Background: The functional and structural abnormalities of cortico-striato-thalamo-cortex have been reported to be associated with the neurobiological basis of obsessive-compulsive disorder (OCD). OCD can also occur in the striatum damaging after brain infarction, which is called OCD caused by physical diseases. The relationship and mechanism between temporal lobe abnormalities and obsessive-compulsive disorder (OCD) are still unclear.
Case presentation: A young male with temporal lobe porencephalypresented with obsessive-compulsive symptoms. The cognition of this OCD participant was not significantly impaired, and his social function was well maintained. After treatment with sertraline, aripiprazole, and fluvoxamine, he was improved but relapsed several times after drug withdrawal. However the effect was still maintained when the drugswas used again.
Conclusion: This is the first case report of obsessive-compulsive symptoms in a OCD individual with left temporal lobe porencephaly. The possible relationship between obsessive-compulsive symptoms and temporal lobe structural abnormalities needs to be further studied. The maintenance treatment and prognosis of organic obsessive-compulsive disorder also deserve further study.
Patient characteristics and influencing factors of CKD, CVD and their comorbidities in the middle-aged and elderly population in China
Authors: Fu Zhike , Gui Chuying , Deng Weitian , Zhou Xiaoshan , Li Huijie , Zhang Di , Wang Zan , Deng Yueyi 
Published: December 2024

Abstract

Background and aims:
Chronic Kidney Disease (CKD) and Cardiovascular Disease (CVD) are significant public health concerns with high morbidity and mortality. The relationship between CKD and CVD and their influencing factors in Chinese middle-aged and elderly people remains underexplored. We hypothesize that some socio-demographic factors, lifestyle factors, and physical condition factors significantly influence the prevalence and comorbidity of CKD and CVD.
Methods
We used data from the China Health and Retirement Longitudinal Study (CHARLS), focusing on adults aged 45 and above. CKD stages were defined based on estimated glomerular filtration rate (eGFR), while CVD status was determined through self-reported diagnosis. Factors considered in the analysis included socio-demographic variables (age, gender, household registration, education, marital status), lifestyle behaviors (smoking, drinking), and physical conditions (body mass index (BMI), blood pressure, blood sugar, blood lipids, serum uric acid).
Results
CVD risk begins in early stages of CKD in the Chinese population. Individuals with characteristics such as hypertension, diabetes, non-rural household registration, abnormal BMI, or low education levels are significantly more likely to develop CKD and its comorbidity with CVD. Both low and high BMI were associated with increased CKD and CVD risk, with low BMI linked to reduced CVD risk in CKD patients.
Conclusion
Socio-demographic and physical factors are critical in managing and preventing CKD and CVD comorbidities. Public health strategies should focus on non-rural and lower-educated populations in Chinese middle-aged and elderly people, and further research is needed to explore mechanisms and interventions.
Differential Gene Expression Analysis and identification of Mitophagy Hub Genes in Cerebral Ischaemic Stroke
Authors: Huang Wenhui , Ye Weijia , Li Keshen 
Published: December 2024

Abstract

Cerebral ischaemic stroke (CIS) is a neurological disorder associated with high mortality and disability rates. Increasing evidence has indicated that mitophagy significantly influences the pathogenesis and outcome of CIS. The aim of the present study was to explore potential relevance of mitophagy-related differentially expressed genes (MRDEGs) associated with CIS.GSE22255, GSE58294, and mitophagy-related genes (MRGs) were obtained from the Gene Expression Omnibus (GEO) database and the R software was used to identify the MRDEGs in CIS. Functional enrichment and protein–protein interaction (PPI) analyses were performed to explore the role of MRDEGs in CIS, and then Cytoscape was utilized to investigate hub MRDEGs. Furthermore, Hub gene–miRNA and hub gene–TF (transcription factor) interaction networks were constructed, and receiver operating characteristic (ROC) analysis and immune cell infiltration were performed. A total of 4803 downregulated genes and 3975 upregulated genes were identified, and these genes were mainly enriched in the autophagy pathway, oxidative stress pathway, genotoxicity pathway, IL-1R pathway, hypoxia pathway, glycolysis pathway and IL-6 pathway. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that MRDEGs were enriched in several enriched terms related to the mitophagy pathway and the NF-κB signalling pathway. Protein‒protein interaction analysis revealed 9 hub genes, namely, CDC37, MAPK14, HDAC6, CSNK2A1, VDAC2, TRAP1, FUNDC1, CHCHD3, and MTX1. It was predicted that 128 transcription factors and 29 miRNAs might interact with the hub genes. ROC analysis revealed that the hub genes in the merged dataset had lower diagnostic value than did the genes in the normal and CIS sample groups. CIBERSORT analysis revealed that infiltration of monocyte- and mast cell-activated M2 macrophages were significantly different between patients with CIS and normal individuals. This study could provide new ideas for further elucidation of the pathogenesis of CIS in the future.
Green Synthesis of Imidazopyridine Tetracyclic Derivatives via the Groebke-Blackburn- Bienaymé Reaction Using Novel Functionalized Cellulose-Based Catalyst
Authors: Ghomi Minoo Khalili , Sayahi Mohammad Hosein , Esmkhani Maryam , Noori Milad , Hashempur Mohammad Hashem , Iraji Aida , Abedinifar Fahimeh , Mahdavi Mohammad , Javanshir Shahrzad 
Published: December 2024

Abstract

The widespread use of petroleum-based products has raised ecological and environmental concerns, leading to increased public interest in utilizing natural resources for the development of functional materials. Cellulose, derived from various biobased sources such as plants, biomass, and bacteria, is emerging as an ideal biomaterial with significant potential for diverse applications due to its efficient, scalable, and straightforward production methods. In this study, we fabricated a novel functionalized cellulose-based catalyst by modifying Pampas Plumes (Cortaderia selloana) with (3-Mercaptopropyl)triethoxysilane (MPTS) and chlorosulfonic acid. The resulting catalyst, termed Pampas@Si/SO3H, was characterized using a range of analytical techniques, including Fourier Transform Infrared (FTIR) spectroscopy, Scanning Electron Microscopy (SEM), Energy-Dispersive X-ray Spectroscopy (EDS), X-ray Powder Diffraction (XRD), and Brunauer − Emmett − Teller (BET) analysis.The synthesized Pampas@Si/SO3H catalyst demonstrated high efficiency as a heterogeneous catalyst in the synthesis of imidazopyridine tetracyclic derivatives via the Groebke-Blackburn-Bienaymé (GBB) reaction. This reaction involves cyclohexyl isocyanide, benzaldehyde derivatives, and various 2-aminopyridines. The advantages of this green synthesis protocol include low catalyst loading, short reaction times, stability, and recyclability for at least four reaction cycles.
Approximating exponentials of commutators by optimized product formulas
Authors: Casas Fernando , Escorihuela-Tomàs Alejandro , Casares Pablo A. Moreno 
Published: December 2024

Abstract

Trotter product formulas constitute a cornerstone quantum Hamiltonian simulation technique. However, the efficient implementation of Hamiltonian evolution of nested commutators remains an under explored area.In this work, we construct optimized product formulas of orders 3 to 6 approximating the exponential of a commutator of two arbitrary operators in terms of the exponentials of the operators involved. The new schemes require a reduced number of exponentials and thus provide more efficient approximations than other previouslypublished alternatives. They can also be used as basic methods in recursive procedures to increasethe order of approximation.We expect this research will improve the efficiency of quantum control protocols, as well as quantum algorithms such as the Zassenhaus-based product formula, Magnus operator-based time-dependent simulation, and product formula schemes with modified potentials.
Chronic Kidney Disease Early Prediction Using Machine Learning
Authors: Alnokta Sarah , Alkuddsi Yanal , Aleinikovas Marius , Silinskas Benas , Almogdad Mohammad , Skema Mindaugas , Almukdad Manal 
Published: December 2024

Abstract

In the human body, the kidneys, play the important role of filtering wastes and toxic bodies from the blood. Chronic kidney disease (CKD) is a condition in which the human kidneys are damaged and unable to filter the blood in a proper way. It is a nontransmissible disease that causes mortality of large numbers worldwide and is very expensive to properly detect and diagnose, therefore, CKD patients often reach its chronic stages, especially in countries with limited resources. Furthermore, CKD is a silent killer due to the lack of physical symptoms at the initial stage, but a steady loss of glomerular filtration rate (GFR) occurs over a period longer than three months. CKD is a fatal disease if left undetected as it leads to renal failure, in the worst cases. However, the early diagnosis of CDK can significantly reduce the mortality rate. Moreover, if CKD is predicted early and correctly, it results in an increased probability of successful treatment and prolongs the patient’s life. The advances in ML, in addition to predictive analytics, provide promising results which in turn prove the capability of prediction in CKD and beyond. The utilization of ML methods in nephrology enables the building of ML models to better detect the at-risk patients of CKD especially in primary care settings. The current study carries out a prediction-based method that helps in early detecting of CKD patients at the early stage. In this study, we utilize on of the boosting method, XGBoost to achieve a higher prediction accuracy for CKD. Various preprocessing steps are employed to achieve better prediction performance, along with suitable hyperparameter tuning and feature selection. We assessed the degree of importance of each feature in the dataset leading to CKD. The performance of the model was evaluated with accuracy. It attained 98% accuracy for training and testing sets. The way the research was done leads to the conclusion that recent improvements in machine learning, along with the help of predictive modeling, make for an interesting way to find new solutions that can then be used to test the accuracy of prediction in the field of kidney disease and beyond.
The length-of-stay associated with adequacy of empirical antimicrobial therapy – systematic reviews with meta-analysis
Authors: Merlos Fernando , Tuon Felipe Francisco 
Published: December 2024

Abstract

Introduction: Infections, particularly sepsis, require rapid initiation of empirical antibiotic therapy. Delays or inadequacies in therapy can significantly increase patient morbidity, mortality, and length of stay (LOS). This systematic review and meta-analysis aimed to evaluate the impact of appropriate versus inappropriate empirical antibiotic therapy on LOS.
Methods: A comprehensive search was conducted in EMBASE, Cochrane Library, Web of Science, and MEDLINE for studies published between 2012 and 2024. Studies involving adult hospitalized patients with infections, assessment of antimicrobial adequacy based on microbiological cultures, and LOS data were included. Statistical analysis was performed using Review Manager 5.3, with LOS treated as a continuous variable and outcomes assessed through mean difference and 95% confidence intervals.
Results: Thirteen studies with a total of 4,572 participants met the inclusion criteria. The mean LOS for patients receiving appropriate therapy was significantly lower than for those receiving inadequate therapy (mean difference -2.07 days; 95% CI: -2.20, -1.95). This reduction in LOS was consistent across different infection sites, including bloodstream infections, sepsis, and intra-abdominal infections. Sensitivity analysis excluding a dominant study still showed a significant reduction in LOS. Additionally, appropriate therapy resulted in a reduced ICU LOS by -0.89 days (95% CI: -1.22, -0.57).
Conclusion: Adequate antimicrobial therapy significantly reduces LOS in hospitalized patients with infections. Early intervention and rapid microbiological diagnosis, especially for multidrug-resistant pathogens, are crucial to optimizing therapy. These findings support the integration of antimicrobial stewardship programs and rapid diagnostic tools to improve patient outcomes and reduce healthcare burdens.
Understanding Global and Regional Homicide Variations: From Education to Governance.
Authors: Croci Gonzalo , Gomez Joel 
Published: December 2024

Abstract

Existing research on the causes of homicide often yields contradictory results, with limited studies focusing on regional contexts. While many analyses are cross-national at the global level, regional studies remain scarce despite critiques highlighting their significance. This study aims to address these gaps by analyzing factors influencing homicide rates globally and regionally, with a focus on the Americas, Africa, Asia, and Europe. We utilize panel regression analysis on a dataset spanning from 2012 to 2021, including variables such as inequality, unemployment, educational attainment, poverty, urbanization, government effectiveness, and corruption. The findings reveal that educational attainment and government effectiveness are significant determinants of homicide rates, particularly in the Americas, while corruption, poverty, and unemployment exert minimal influence. These results underscore the critical role of institutional effectiveness and education in mitigating violence and highlight the need for region-specific policy interventions. Word count: 8,299
Grey or Green: Investigating the Urban Rivers’ Landscapes along the Capital Cities of Western Balkans
Authors: Pilua Arjola , Hysa Artan , Kader Shuraik , Zejnilovic Emina , Tariq Aqil , Sestras Paul , Teqja Zydi 
Published: December 2024

Abstract

Urban watercourses are vital natural elements within cities that can provide multiple ecosystem services to society. However, rivers are under continuous urbanization pressures in developing urban areas like the post-socialist countries. We focus on the Western Balkans (WB) countries to assess the relationship between the urban rivers and the respective metropolitan capital areas. First, we analyze the land use and land cover (LULC) along the respective watercourse at five buffer distances. Our work relies on Urban Atlas data acquired from the European Environment Agency. According to our results the natural land surfaces share on the waterfronts range between 89% along Lana River (Tirana) and 22% along Miljacka River (Sarajevo). The green surfaces share along the Moraca River (Podgorica) and Vardar River (Skopje) are more constant along five buffer distances. We report the results of each case in detail and compare among the selected five developing European urban centers with respect to their unique socio-political background. Our findings highlight the importance of natural and semi-natural surfaces presence along the urban rivers in support of sustainable decision-making at multiple spatial and jurisdiction levels in the WB, which is a hotspot of political, economic, and urban transformation triggered by the EU membership aspirations.
Wastewater microbiology: occurrence and prevalence of antibiotic-resistant extended-spectrum β-lactamase-producing Enterobacteriaceae in the district wastewater system
Authors: Mohany Mohamed , Aslam Jawad , Ali Muhammad Adnan , Khattak Baharullah , Fozia Fozia , Ahmad Ijaz , Khan Muhammad Daud , Al-Rejaie Salim S. , Ziaullah Ziaullah , Milošević Marija 
Published: December 2024

ABSTRACT

Extended spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, including Klebsiella pneumoniae and Escherichia coli, pose a serious risk to human health because of antibiotic resistance. Wastewater serves as a reservoir for these bacteria, contributing to the evolution and transmission of antibiotic-resistant strains. The research aims to identify ESBL bacterium in wastewater samples from District Kohat. K. pneumoniae and E. coli were confirmed as ESBL-producing bacteria through a comprehensive array of diagnostic procedures, including Gram staining, biochemical analyses, and antibiotic susceptibility testing. Fecal coliform count (FCC) analyses revealed varying microorganism levels. Both E. coli and K. pneumoniae isolates showed ESBL enzyme expression, indicating antibiotic resistance. Resistance patterns included ciprofloxacin, ampicillin, cefotaxime, cefoxitin, and amoxicillin-clavulanic acid for both species. E. coli displayed higher sensitivity for chloramphenicol, trimethoprim- sulfamethoxazole, and gentamicin. Ceftazidime minimum inhibitory concentration results showed E. coli's higher resistance. The study accentuates the presence of antibiotic-resistant strains, emphasizing the value of effective wastewater treatment. The study provides crucial insights into microbial characteristics, fecal contamination, ESBL production, and antibiotic resistance in E. coli and K. pneumoniae isolates, advocating for monitoring and mitigation strategies.
Exploring the Lived Experiences of Clinical Educators: Challenges, Motivations, and Future Perspectives
Authors: Azhar Farah , Adnan Nooreen , Ahmed Lubna , Rubaba Azim Syeda 
Published: December 2024

Introduction:
This study examines the factors contributing to the shortage of medical doctors teaching medical students despite their crucial role in training the
future medical workforce.

Methods:
To analyze the factors behind the lack of medical doctors in the training of medical students, we used ‘phenomenology’ to understand clinical
educators' lived experiences and their constructed meanings. Within the domain of phenomenology, we applied hermeneutic (interpretive)
phenomenology. The experiences of eight clinical educators at the Gulf Medical University were explored through interviews and analyzed using
Interpretative Phenomenological Analysis (IPA) and Socio-Cognitive Career Theory (SCCT).

Results:
The findings revealed that entry into medical education often occurred serendipitously due to inadequate career counseling and the undervaluation
of the field. Acquiring a postgraduate medical education qualification in medical education enhanced one’s professional life and fostered a sense of
identity as a clinical educator. Key motivators included a passion for the field, student interaction, support from colleagues, and an encouraging
working environment. Clinical educators faced challenges, such as the field's low value, vague professional identity, delays in promotion,
specifically in UAE, low income, and insufficient dedicated teaching time. Coping strategies involved cultivating a positive work environment and
maintaining optimism. Growing awareness and a positive outlook for medical education were noted.

Conclusion:
This study uncovered the underlying issues faced by clinical educators through their lived experiences. To change the status quo, we propose
facilitating medical students and young doctors in joining this field early in their careers through strong career counseling and advocating clear
entry and progression pathways. Young medical educators should be facilitated by providing an encouraging environment, acknowledging their
medical education-related qualifications, and improving remuneration.