bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved Cardiac Function in Postischemic Rats Using an Optimized Cardiac Reprogramming Cocktail Delivered in a Single Novel Adeno-Associated Virus
Authors: Zhou Huanyu , Yang Jin , Srinath Chetan , Zeng Aliya , Wu Iris , Leon Elena C. , Qureshi Tawny Neal , Reid Christopher A. , Nettesheim Emily R. , Xu Emma , Duclos Zoe , Mohamed Tamer M.A. , Farshidfar Farshad , Fejes Anthony , Liu Jun , Jones Samantha , Feathers Charles , Chung Tae Won , Jing Frank , Prince William S. , Lin JianMin , Yu Pengzhi , Srivastava Deepak , Hoey Timothy , Ivey Kathryn N. , Lombardi Laura M. 
Published: August 2023

BACKGROUND:
Cardiac reprogramming is a technique to directly convert nonmyocytes into myocardial cells using genes or small molecules. This intervention provides functional benefit to the rodent heart when delivered at the time of myocardial infarction or activated transgenically up to 4 weeks after myocardial infarction. Yet, several hurdles have prevented the advancement of cardiac reprogramming for clinical use.

METHODS:
Through a combination of screening and rational design, we identified a cardiac reprogramming cocktail that can be encoded in a single adeno-associated virus. We also created a novel adeno-associated virus capsid that can transduce cardiac fibroblasts more efficiently than available parental serotypes by mutating posttranslationally modified capsid residues. Because a constitutive promoter was needed to drive high expression of these cell fate–altering reprogramming factors, we included binding sites to a cardiomyocyte-restricted microRNA within the 3’ untranslated region of the expression cassette that limits expression to nonmyocytes. After optimizing this expression cassette to reprogram human cardiac fibroblasts into induced cardiomyocyte-like cells in vitro, we also tested the ability of this capsid/cassette combination to confer functional benefit in acute mouse myocardial infarction and chronic rat myocardial infarction models.

RESULTS:
We demonstrated sustained, dose-dependent improvement in cardiac function when treating a rat model 2 weeks after myocardial infarction, showing that cardiac reprogramming, when delivered in a single, clinically relevant adeno-associated virus vector, can support functional improvement in the postremodeled heart. This benefit was not observed with GFP (green fluorescent protein) or a hepatocyte reprogramming cocktail and was achieved even in the presence of immunosuppression, supporting myocyte formation as the underlying mechanism.

CONCLUSIONS:
Collectively, these results advance the application of cardiac reprogramming gene therapy as a viable therapeutic approach to treat chronic heart failure resulting from ischemic injury.
On the mechanical properties and vibrational characteristics of the nanoparticle-reinforced composite cylindrical panels in the acidic environment: Numerical and experimental investigation
Authors: Alinia Maysam , Saber-Samandari Saeed , Sadough Vanini Seyyed Ali 
Published: August 2023

The purpose of this study is to determine the impact of nano-clay and nano-silica particles on the vibrational characteristics of composite cylindrical panels in corrosive environments. In this context, due to the presence of diluted sulfuric acid as the corrosive solution, the coupling effects of material degradation and hygroscopic loading on the natural frequencies are taken into consideration. In order to achieve this, it is first explored through experiment how adding nanoparticles affects the coefficient of hygroscopic expansion of the glass/epoxy specimens. Using this coefficient, the in-plane loading caused by corrosive solution is then applied in the equations. The mechanical properties and hygroscopic expansion coefficients of the composite samples exposed to the corrosive environment are first determined by certain experimental testing. The equations of motion are derived using the first-order shear deformation theory (FSDT), and the vibration problem is solved using the generalized differential quadrature (GDQ) technique. Investigation is conducted into the effects of various nanoparticles, immersion time, geometrical elements, and boundary conditions on the natural frequencies of the cylindrical panels. It is found that adding nanoparticles can significantly improve the mechanical properties, the corrosion resistance, and the natural frequencies of composites in which the nano-clay is more effective. For example, adding nano-clay and nano-silica particles, respectively, results in 32.32% and 26.29% increase in elasticity modulus of reinforced glass/epoxy composite. In addition, 12.71% and 47.32% improvements are observed in the natural frequency of the nano-clay reinforced composite panel before and after 90 days of immersion in sulfuric acid. In comparison, the nano-silica particles are responsible for 7.80% and 23.03% increase in natural frequency before and after immersion time.
Prevalence of Failed Back Surgery Syndrome Across Hospital Corporation of America Healthcare in the United States, Their Correlation With Mood Disorders and Other Lifestyle-Related Comorbidities
Authors: Gonzalez-Ramos Keysha , Hanif Zainab , Shahid Maham , Guzman Nilmarie , Hurlock Natalie P. 
Published: August 2023

About 16 million adults present with chronic back pain, the sixth most costly condition in the United States (US). Estimates suggest that about 60% of initial back surgeries have a successful outcome; however, many don’t, leaving over 80,000 failed back surgeries per year. Failed Back Surgery Syndrome (FBSS) is defined by the International Association for the Study of Pain as back pain, with or without radiating pain, located in the lower limbs, of unknown origin, which persists or begins after surgical procedures are performed to treat lumbar disc herniations. Psychiatric comorbidities and psychosocial factors have been associated with patients presenting with this syndrome. A retrospective cross-sectional study was performed to identify the prevalence of FBSS in a population of patients during the period of January 2019-December 2020 across Hospital Corporation of America (HCA) Healthcare in the US. With a sample of 28,426 patients who underwent back surgery only 8% had FBSS. Those with FBSS (N = 2434) were mainly females (54.27%) with a mood disorder (61.18%), P-value <.0001. Among those with FBSS, there was a statistically significant relationship between mood disorder and smoking (57.37%) and obesity (54.61%) compared to non-smokers and non-obese. Lifestyle interventions may ameliorate disabling symptoms and improve the well-being of this population.
How suitable are clinical vignettes for the evaluation of symptom checker apps? A test theoretical perspective
Authors: Kopka Marvin , Feufel Markus A , Berner Eta S , Schmieding Malte L 
Published: August 2023

Objective To evaluate the ability of case vignettes to assess the performance of symptom checker applications and to suggest refinements to the methodology used in case vignette-based audit studies. Methods We re-analyzed the publicly available data of two prominent case vignette-based symptom checker audit studies by calculating common metrics of test theory. Furthermore, we developed a new metric, the Capability Comparison Score (CCS), which compares symptom checker capability while controlling for the difficulty of the set of cases each symptom checker evaluated. We then scrutinized whether applying test theory and the CCS altered the performance ranking of the investigated symptom checkers. Results In both studies, most symptom checkers changed their rank order when adjusting the triage capability for item difficulty (ID) with the CCS. The previously reported triage accuracies commonly overestimated the capability of symptom checkers because they did not account for the fact that symptom checkers tend to selectively appraise easier cases (i.e., with high ID values). Also, many case vignettes in both studies showed insufficient (very low and even negative) values of item-total correlation (ITC), suggesting that individual items or the composition of item sets are of low quality. Conclusions A test–theoretic perspective helps identify previously undetected threats to the validity of case vignette-based symptom checker assessments and provides guidance and specific metrics to improve the quality of case vignettes, in particular by controlling for the difficulty of the vignettes an app was (not) able to evaluate correctly. Such measures might prove more meaningful than accuracy alone for the competitive assessment of symptom checkers. Our approach helps elaborate and standardize the methodology used for appraising symptom checker capability, which, ultimately, may yield more reliable results.
A model for the dissemination of circulating tumour cell clusters involving platelet recruitment and a plastic switch between cooperative and individual behaviours
Authors: Hapeman Jorian D. , Carneiro Caroline S. , Nedelcu Aurora M. 
Published: August 2023

Abstract
Background
In spite of extensive research, cancer remains a major health problem worldwide. As cancer progresses, cells acquire traits that allow them to disperse and disseminate to distant locations in the body – a process known as metastasis. While in the vasculature, these cells are referred to as circulating tumour cells (CTCs) and can manifest either as single cells or clusters of cells (i.e., CTC clusters), with the latter being the most aggressive. The increased metastatic potential of CTC clusters is generally associated with cooperative group benefits in terms of survival, including increased resistance to shear stress, anoikis, immune attacks and drugs. However, the adoption of a group phenotype poses a challenge when exiting the vasculature (extravasation) as the large size can hinder the passage through vessel walls. Despite their significant role in the metastatic process, the mechanisms through which CTC clusters extravasate remain largely unknown. Based on the observed in vivo association between CTC clusters and platelets, we hypothesized that cancer cells take advantage of the platelet-derived Transforming Growth Factor Beta 1 (TGF-β1) – a signalling factor that has been widely implicated in many aspects of cancer, to facilitate their own dissemination. To address this possibility, we evaluated the effect of exogenous TGF-β1 on an experimentally evolved non-small cell lung cancer cell line that we previously developed and used to investigate the biology of CTC clusters.

Results
We found that exogenous TGF-β1 induced the dissociation of clusters in suspension into adherent single cells. Once adhered, cells released their own TGF-β1 and were able to individually migrate and invade in the absence of exogenous TGF-β1. Based on these findings we developed a model that involves a TGF-β1-mediated plastic switch between a cooperative phenotype and a single-celled stage that enables the extravasation of CTC clusters.

Conclusions
This model allows for the possibility that therapies can be developed against TGF-β1 signalling components and/or TGF-β1 target genes to suppress the metastatic potential of CTC clusters. Considering the negative impact that metastasis has on cancer prognosis and the lack of therapies against this process, interfering with the ability of CTC clusters to switch between cooperative and individual behaviours could provide new strategies to improve patient survival.
Spatio-temporal home range of the dominant rodent species in Mabira central forest reserve, Uganda
Authors: Ssuuna James , Makundi Rhodes H. , Chidodo Simon J. , Isabirye Moses , Mbije Nsajigwa E. , Mulungu Loth S. 
Published: August 2023

Abstract
Background
Rodents form the largest order among mammals in terms of species diversity, and home range is the area where an individual normally moves during its normal daily activities. Information about rodent home ranges is paramount in the development of effective conservation and management strategies. This is because rodent home range varies within species and different habitats. In Uganda, tropical high altitude forests such as the Mabira Central Forest Reserve are experiencing continuous disturbance. However, information on rodent home range is lacking. Therefore, a two year Capture-Mark-Release (CMR) of rodents was conducted in the intact forest habitat: Wakisi, regenerating forest habitat: Namananga, and the depleted forest habitat: Namawanyi of Mabira Central Forest Reserve in order to determine the dominant rodent species, their home ranges, and factors affecting these home ranges. The home ranges were determined by calculating a minimum convex polygon with an added boundary strip of 5 m.

Results
Overall, the most dominant rodent species were: Lophuromys stanleyi, Hylomyscus stella, Praomys jacksoni Mastomys natalensis, Lophuromys ansorgei, and Lemniscomys striatus. H. stella dominated the intact forest habitat, while L. stanleyi was the most dominant both in the regenerating and the depleted forest habitats. L. stanleyi had a larger home range in the depleted forest, and the regenerating forest habitats, respectively. In the regenerating forest habitat, M. natalensis had a larger home range size, followed by L. stanleyi, and L. striatus. While in the intact forest habitat, H. stella had the largest home range followed by P. jacksoni. H. stella, L. striatus, L. stanleyi, M. natalensis, and P. jacksoni were most dominant during the wet season while L. ansorgei was relatively more dominant during the dry season. L. ansorgei, and P. jacksoni had a larger home range in the dry season, and a lower home range in the wet season. H. stella, L. stanleyi, M. natalansis and L.striatus had larger home ranges in the wet season, and lower home ranges in the dry season.
The home ranges of the dominant rodent species varied across the three habitats in Mabira central forest reserve ($${F}_{(2, 15)}= 6.41$$

F

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2
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15
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=
6.41

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0.000

).

Conclusion
The significant variation in home ranges of the dominant rodent species in Mabira Central Forest Reserve depending on the type of habitat presupposes that the rodent management strategies in disturbed forest reserves should focus on the type of habitat.
High-fat diet in early life triggers both reversible and persistent epigenetic changes in the medaka fish (Oryzias latipes)
Authors: Inoue Yusuke , Suzuki Yuta , Kunishima Yoshimi , Washio Terumi , Morishita Shinichi , Takeda Hiroyuki 
Published: August 2023

Abstract
Background
The nutritional status during early life can have enduring effects on an animal’s metabolism, although the mechanisms underlying these long-term effects are still unclear. Epigenetic modifications are considered a prime candidate mechanism for encoding early-life nutritional memories during this critical developmental period. However, the extent to which these epigenetic changes occur and persist over time remains uncertain, in part due to challenges associated with directly stimulating the fetus with specific nutrients in viviparous mammalian systems.

Results
In this study, we used medaka as an oviparous vertebrate model to establish an early-life high-fat diet (HFD) model. Larvae were fed with HFD from the hatching stages (one week after fertilization) for six weeks, followed by normal chow (NC) for eight weeks until the adult stage. We examined the changes in the transcriptomic and epigenetic state of the liver over this period. We found that HFD induces simple liver steatosis, accompanied by drastic changes in the hepatic transcriptome, chromatin accessibility, and histone modifications, especially in metabolic genes. These changes were largely reversed after the long-term NC, demonstrating the high plasticity of the epigenetic state in hepatocytes. However, we found a certain number of genomic loci showing non-reversible epigenetic changes, especially around genes related to cell signaling, liver fibrosis, and hepatocellular carcinoma, implying persistent changes in the cellular state of the liver triggered by early-life HFD feeding.

Conclusion
In summary, our data show that early-life HFD feeding triggers both reversible and persistent epigenetic changes in medaka hepatocytes. Our data provide novel insights into the epigenetic mechanism of nutritional programming and a comprehensive atlas of the long-term epigenetic state in an early-life HFD model of non-mammalian vertebrates.
Visualizing and exploring patterns of large mutational events with SigProfilerMatrixGenerator
Authors: Khandekar Azhar , Vangara Raviteja , Barnes Mark , Díaz-Gay Marcos , Abbasi Ammal , Bergstrom Erik N. , Steele Christopher D. , Pillay Nischalan , Alexandrov Ludmil B. 
Published: August 2023

Abstract
Background
All cancers harbor somatic mutations in their genomes. In principle, mutations affecting between one and fifty base pairs are generally classified as small mutational events. Conversely, large mutational events affect more than fifty base pairs, and, in most cases, they encompass copy-number and structural variants affecting many thousands of base pairs. Prior studies have demonstrated that examining patterns of somatic mutations can be leveraged to provide both biological and clinical insights, thus, resulting in an extensive repertoire of tools for evaluating small mutational events. Recently, classification schemas for examining large-scale mutational events have emerged and shown their utility across the spectrum of human cancers. However, there has been no computationally efficient bioinformatics tool that allows visualizing and exploring these large-scale mutational events.

Results
Here, we present a new version of SigProfilerMatrixGenerator that now delivers integrated capabilities for examining large mutational events. The tool provides support for examining copy-number variants and structural variants under two previously developed classification schemas and it supports data from numerous algorithms and data modalities. SigProfilerMatrixGenerator is written in Python with an R wrapper package provided for users that prefer working in an R environment.

Conclusions
The new version of SigProfilerMatrixGenerator provides the first standardized bioinformatics tool for optimized exploration and visualization of two previously developed classification schemas for copy number and structural variants. The tool is freely available at https://github.com/AlexandrovLab/SigProfilerMatrixGenerator with an extensive documentation at https://osf.io/s93d5/wiki/home/.
Long-term inorganic nitrate administration protects against myocardial ischemia-reperfusion injury in female rats
Authors: Yassaghi Younes , Jeddi Sajad , Yousefzadeh Nasibeh , Kashfi Khosrow , Ghasemi Asghar 
Published: August 2023

Abstract
Background
The favorable effects of nitrate against myocardial ischemia-reperfusion injury (MIRI) have primarily focused on male rats and in short term. Here we determine the impact of long-term nitrate intervention on baseline cardiac function and the resistance to MIRI in female rats.

Methods
Female Wistar rats were randomly divided into untreated and nitrate-treated (100 mg/L sodium nitrate in drinking water for 9 months) groups (n = 14/group). At intervention end, levels of serum progesterone, nitric oxide metabolites (NOx), heart NOx concentration, and mRNA expressions of NO synthase isoforms (NOS), i.e., endothelial (eNOS), neuronal (nNOS), and inducible (iNOS), were measured. Isolated hearts were exposed to ischemia, and cardiac function indices (CFI) recorded. When the ischemia-reperfusion (IR) period ended, infarct size, NO metabolites, eNOS, nNOS, and iNOS expression were measured.

Results
Nitrate-treated rats had higher serum progesterone (29.8%, P = 0.013), NOx (31.6%, P = 0.035), and higher heart NOx (60.2%, P = 0.067), nitrite (131%, P = 0.018), and eNOS expression (200%, P = 0.005). Nitrate had no significant effects on baseline CFI but it increased recovery of left ventricular developed pressure (LVDP, 19%, P = 0.020), peak rate of positive (+ dp/dt, 16%, P = 0.006) and negative (–dp/dt, 14%, P = 0.014) changes in left ventricular pressure and decreased left ventricular end-diastolic pressure (LVEDP, 17%, P < 0.001) and infarct size (34%, P < 0.001). After the IR, the two groups had significantly different heart nitrite, nitrate, NOx, and eNOS and iNOS mRNA expressions.

Conclusions
Long-term nitrate intervention increased the resistance to MIRI in female rats; this was associated with increased heart eNOS expression and circulating progesterone before ischemia and blunting ischemia-induced increased iNOS and decreased eNOS after MIRI.
A systematic review and meta-analysis of cardiovascular diseases and associated factors among diabetes mellitus patients in Ethiopia
Authors: Ayalew Tadele Lankrew , Haile Kirubel Eshetu , Feleke Mulualem Gete , Zewudie Bitew Tefera , Chichiabellu Tesfaye Yitna 
Published: August 2023

Abstract
Background
Cardiovascular disease (CVD) is the most prevalent complication and the leading cause of death and disability among patients with diabetes mellitus (DM). Over time, diabetes-related cardiovascular disease has become more common worldwide. The aim of this study was to determine the cumulative prevalence of cardiovascular disease and associated factors among diabetic patients in Ethiopia.

Objective
The main aim of this review was to estimate the pooled prevalence of cardiovascular disease and its associated factors among diabetic patients in Ethiopia.

Methods and materials
This review was searched using PubMed, Google, and Google Scholar search engines, and was accessed using medical subject heading (MeSH) terms for studies based in Ethiopia. Excel was used to extract the data. With a random-effects model, STATA Version 14 was used for all statistical analyses. The studies' heterogeneity and funnel plot were both examined. The study domain and authors' names were used in the subgroup analysis.

Results
In this systematic review, 12 studies totaling 2,953 participants were included. The estimated overall prevalence of cardiovascular disease among diabetic patients in Ethiopia was 37.26% (95% CI: 21.05, 53.47, I2 = 99.3%, P ≤ 0.001). Study participants’ age older than 60 years (AOR = 4.74, 95%CI: 1.05, 8.43), BMI > 24.9kg/m2 (AOR = 4.12, 95% CI: 2.33, 5.92), triglyceride > 200mg/dl (AOR = 3.05, 95% CI: 1.26, 4.83), Hypertension (AOR = 3.26, 95% CI: 1.09, 5.43) and duration of DM > 4 years (AOR = 5.49, 95% CI: 3.27, 7.70) were significantly associated with cardiovascular disease.

Conclusions
In conclusion, diabetic patients face a serious public health risk from cardiovascular disease. This review found the following factors, which is independent predictors of cardiovascular disease in diabetic patients: age over 60, BMI > 24.9kg/m2, triglycerides > 200 mg/dl, hypertension, and diabetes duration > 4 years. The results emphasize the need for a prospective study design with a longer follow-up period to assess the long-term effects of CVD predictors in diabetic patients as well as the significance of paying attention to cardiovascular disease in diabetic patients with comorbidity.