bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent advances in the discovery and development of drugs targeting the kallikrein-kinin system
Authors: Wisniewski Petra , Gangnus Tanja , Burckhardt Bjoern B. 
Published: April 2024

Abstract
Background
The kallikrein-kinin system is a key regulatory cascade involved in blood pressure maintenance, hemostasis, inflammation and renal function. Currently, approved drugs remain limited to the rare disease hereditary angioedema. However, growing interest in this system is indicated by an increasing number of promising drug candidates for further indications.

Methods
To provide an overview of current drug development, a two-stage literature search was conducted between March and December 2023 to identify drug candidates with targets in the kallikrein-kinin system. First, drug candidates were identified using PubMed and Clinicaltrials.gov. Second, the latest publications/results for these compounds were searched in PubMed, Clinicaltrials.gov and Google Scholar. The findings were categorized by target, stage of development, and intended indication.

Results
The search identified 68 drugs, of which 10 are approved, 25 are in clinical development, and 33 in preclinical development. The three most studied indications included diabetic retinopathy, thromboprophylaxis and hereditary angioedema. The latter is still an indication for most of the drug candidates close to regulatory approval (3 out of 4). For the emerging indications, promising new drug candidates in clinical development are ixodes ricinus-contact phase inhibitor for thromboprophylaxis and RZ402 and THR-149 for the treatment of diabetic macular edema (all phase 2).

Conclusion
The therapeutic impact of targeting the kallikrein-kinin system is no longer limited to the treatment of hereditary angioedema. Ongoing research on other diseases demonstrates the potential of therapeutic interventions targeting the kallikrein-kinin system and will provide further treatment options for patients in the future.
CAV3 alleviates diabetic cardiomyopathy via inhibiting NDUFA10-mediated mitochondrial dysfunction
Authors: Guo Ping , Hu Shuiqing , Liu Xiaohui , He Miaomiao , Li Jie , Ma Tingqiong , Huang Man , Fang Qin , Wang Yan 
Published: April 2024

Abstract
Background
The progression of diabetic cardiomyopathy (DCM) is noticeably influenced by mitochondrial dysfunction. Variants of caveolin 3 (CAV3) play important roles in cardiovascular diseases. However, the potential roles of CAV3 in mitochondrial function in DCM and the related mechanisms have not yet been elucidated.

Methods
Cardiomyocytes were cultured under high-glucose and high-fat (HGHF) conditions in vitro, and db/db mice were employed as a diabetes model in vivo. To investigate the role of CAV3 in DCM and to elucidate the molecular mechanisms underlying its involvement in mitochondrial function, we conducted Liquid chromatography tandem mass spectrometry (LC–MS/MS) analysis and functional experiments.

Results
Our findings demonstrated significant downregulation of CAV3 in the cardiac tissue of db/db mice, which was found to be associated with cardiomyocyte apoptosis in DCM. Importantly, cardiac-specific overexpression of CAV3 effectively inhibited the progression of DCM, as it protected against cardiac dysfunction and cardiac remodeling associated by alleviating cardiomyocyte mitochondrial dysfunction. Furthermore, mass spectrometry analysis and immunoprecipitation assays indicated that CAV3 interacted with NDUFA10, a subunit of mitochondrial complex I. CAV3 overexpression reduced the degradation of lysosomal pathway in NDUFA10, restored the activity of mitochondrial complex I and improved mitochondrial function. Finally, our study demonstrated that CAV3 overexpression restored mitochondrial function and subsequently alleviated DCM partially through NDUFA10.

Conclusions
The current study provides evidence that CAV3 expression is significantly downregulated in DCM. Upregulation of CAV3 interacts with NDUFA10, inhibits the degradation of lysosomal pathway in NDUFA10, a subunit of mitochondrial complex I, restores the activity of mitochondrial complex I, ameliorates mitochondrial dysfunction, and thereby protects against DCM. These findings indicate that targeting CAV3 may be a promising approach for the treatment of DCM.
An implementation analysis of a quality improvement project to reduce cesarean section in Brazilian private hospitals
Authors: Torres Jacqueline Alves , Leite Tatiana Henriques , Fonseca Thaís Cristina Oliveira , Domingues Rosa Maria Soares Madeira , Figueiró Ana Claudia , Pereira Ana Paula Esteves , Theme-Filha Mariza Miranda , da Silva Ayres Bárbara Vasques , Scott Oliver , de Cássia Sanchez Rita , Borem Paulo , de Maio Osti Maria Carolina , Rosa Marcos Wengrover , Andrade Amanda S. , Filho Fernando Maia Peixoto , Nakamura-Pereira Marcos , do Carmo Leal Maria 
Published: April 2024

Abstract
Background
Brazil has one of the highest prevalence of cesarean sections in the world. The private health system is responsible for carrying out most of these surgical procedures. A quality improvement project called Adequate Childbirth Project (“Projeto Parto Adequado”- PPA) was developed to identify models of care for labor and childbirth, which place value on vaginal birth and reduce the frequency of cesarean sections without a clinical indication. This research aims to evaluate the implementation of PPA in private hospitals in Brazil.

Method
Evaluative hospital-based survey, carried out in 2017, in 12 private hospitals, including 4,322 women. We used a Bayesian network strategy to develop a theoretical model for implementation analysis. We estimated and compared the degree of implementation of two major driving components of PPA—“Participation of women” and “Reorganization of care” – among the 12 hospitals and according to type of hospital (belonging to a health insurance company or not). To assess whether the degree of implementation was correlated with the rate of vaginal birth data we used the Bayesian Network and compared the difference between the group “Exposed to the PPA model of care” and the group “Standard of care model”.

Results
PPA had a low degree of implementation in both components “Reorganization of Care” (0.17 – 0.32) and “Participation of Women” (0.21 – 0.34). The combined implementation score was 0.39–0.64 and was higher in hospitals that belonged to a health insurance company. The vaginal birth rate was higher in hospitals with a higher degree of implementation of PPA.

Conclusion
The degree of implementation of PPA was low, which reflects the difficulties in changing childbirth care practices. Nevertheless, PPA increased vaginal birth rates in private hospitals with higher implementation scores. PPA is an ongoing quality improvement project and these results demonstrate the need for changes in the involvement of women and the care offered by the provider.
Yu Linzhu alleviates primary ovarian insufficiency in a rat model by improving proliferation and energy metabolism of granulosa cells through hif1α/cx43 pathway
Authors: Ruan Xin , Wang Pengxu , Wei Maolin , Yang Qingqing , Dong Xiaoying 
Published: April 2024

Abstract
Background
Yu Linzhu (YLZ) is a classical Chinese traditional formula, which has been used for more than 600 years to regulate menstruation to help pregnancy. However, the mechanism of modern scientific action of YLZ needs to be further studied.

Methods
Thirty SD female rats were divided into three groups to prepare the blank serum and drug-containing serum, and then using UHPLC-QE-MS to identify the ingredients of YLZ and its drug-containing serum. Twenty-four SD female rats were divided into four groups, except the control group, 4-vinylcyclohexene dicycloxide (VCD) was intraperitoneally injected to establish a primary ovarian insufficiency (POI) model of all groups. Using vaginal smear to show that the estrous cycle of rats was disturbed after modeling, indicates that the POI model was successfully established. The ELISA test was used to measure the follicle-stimulating hormone (FSH), estradiol (E2), and anti-Mullerian hormone (AMH) levels in the serum of rats. HE stain was used to assess the morphology of ovarian tissue. The localization and relative expression levels of CX43 protein were detected by tissue immunofluorescence. Primary ovarian granulosa cells (GCs) were identified by cellular immunofluorescence. CCK8 was used to screen time and concentration of drug-containing serum and evaluate the proliferation effect of YLZ on VCD-induced GCs. ATP kit and Seahorse XFe24 were used to detect energy production and real-time glycolytic metabolism rate of GCs. mRNA and protein expression levels of HIF1α, CX43, PEK, LDH, HK1 were detected by RT-PCR and WB.

Results
UHPLC-QE-MS found 1702 ingredients of YLZ and 80 constituents migrating to blood. YLZ reduced the FSH while increasing the AMH and E2 levels. In ovarian tissues, YLZ improved ovarian morphology, follicle development, and the relative expression of CX43. In vitro studies, we found that YLZ increased the proliferative activity of GCs, ATP levels, glycolytic metabolic rate, HIF1α, CX43, PEK, HK1, LDH mRNA, and protein levels.

Conclusions
The study indicated that YLZ increased the proliferation and glycolytic energy metabolism of GCs to improve follicular development further alleviating ovarian function.
The association between triglyceride glucose-body Mass Index and in vitro fertilization outcomes in women with polycystic ovary syndrome: a cohort study
Authors: Li Xin , Luan Ting , Wei Yi , Zhang JuanJuan , Zhao Chun , Ling Xiufeng 
Published: April 2024

Abstract
Background
Polycystic Ovary Syndrome (PCOS) is a common reproductive disorder that frequently affects fertility. The TyG-BMI (Triglyceride glucose-body mass) index is a newly explored parameter that may be linked to reproductive results in individuals with PCOS. Nevertheless, its connection with outcomes in In Vitro Fertilization (IVF) procedures remains uncertain.

Methods
This study included a total of 966 females who underwent IVF treatments for PCOS. At the baseline, the participants were categorized into four groups according to the quartiles of TyG-BMI measured prior to oocyte retrieval. Subsequently, the study compared the differences in clinical and laboratory outcomes among these four groups.

Results
Patients in higher TyG-BMI quartiles exhibited a decreased number of retrieved oocytes, 2PN embryos, and available/high-quality embryos (P < 0.05 for Q1-Q4). Additionally, the multivariable regression analysis revealed that individuals in the top quartile of TyG-BMI had a lower count of accessible embryos (β = -0.224, P = 0.257) and a decreased number of high-quality embryos (β = -0.352, P = 0.028) in comparison to those in the lowest quartile. Nevertheless, there were no notable variances detected in the rates of pregnancy or live births among these quartiles. Furthermore, a linear correlation was noted between the TyG-BMI index and the quantity of accessible embryos (P-non-linear = 0.6, P-overall < 0.001), along with high-quality embryos (P-nonlinear = 0.026, P-overall = 0.006). In contrast, there was no notable linear correlation found between the TyG-BMI index and the available embryo rate (P-nonlinear = 0.60, P-overall = 0.8).

Conclusions
The results of this research emphasize the notable correlation between TyG-BMI and IVF results in females diagnosed with PCOS. The interplay of insulin resistance and disorders of lipid metabolism may indeed play a pivotal role in influencing the assisted reproductive outcomes of patients with PCOS. Considering these findings, TyG-BMI proves to be a valuable indicator for exploring this potential association.
NextDenovo: an efficient error correction and accurate assembly tool for noisy long reads
Authors: Hu Jiang , Wang Zhuo , Sun Zongyi , Hu Benxia , Ayoola Adeola Oluwakemi , Liang Fan , Li Jingjing , Sandoval José R. , Cooper David N. , Ye Kai , Ruan Jue , Xiao Chuan-Le , Wang Depeng , Wu Dong-Dong , Wang Sheng 
Published: April 2024

AbstractLong-read sequencing data, particularly those derived from the Oxford Nanopore sequencing platform, tend to exhibit high error rates. Here, we present NextDenovo, an efficient error correction and assembly tool for noisy long reads, which achieves a high level of accuracy in genome assembly. We apply NextDenovo to assemble 35 diverse human genomes from around the world using Nanopore long-read data. These genomes allow us to identify the landscape of segmental duplication and gene copy number variation in modern human populations. The use of NextDenovo should pave the way for population-scale long-read assembly using Nanopore long-read data.
Enhancing prime editor flexibility with coiled-coil heterodimers
Authors: Mu Shuangshuang , Chen Huangyao , Li Qianru , Gou Shixue , Liu Xiaoyi , Wang Junwei , Zheng Wei , Chen Menglong , Jin Qin , Lai Liangxue , Wang Kepin , Shi Hui 
Published: April 2024

AbstractBackgroundPrime editing enables precise base substitutions, insertions, and deletions at targeted sites without the involvement of double-strand DNA breaks or exogenous donor DNA templates. However, the large size of prime editors (PEs) hampers their delivery in vivo via adeno-associated virus (AAV) due to the viral packaging limit. Previously reported split PE versions provide a size reduction, but they require intricate engineering and potentially compromise editing efficiency.ResultsHerein, we present a simplified split PE named as CC-PE, created through non-covalent recruitment of reverse transcriptase to the Cas9 nickase via coiled-coil heterodimers, which are widely used in protein design due to their modularity and well-understood sequence-structure relationship. We demonstrate that the CC-PE maintains or even surpasses the efficiency of unsplit PE in installing intended edits, with no increase in the levels of undesired byproducts within tested loci amongst a variety of cell types (HEK293T, A549, HCT116, and U2OS). Furthermore, coiled-coil heterodimers are used to engineer SpCas9-NG-PE and SpRY-PE, two Cas9 variants with more flexible editing scope. Similarly, the resulting NG-CC-PE and SpRY-CC-PE also achieve equivalent or enhanced efficiency of precise editing compared to the intact PE. When the dual AAV vectors carrying CC-PE are delivered into mice to target thePcsk9gene in the liver, CC-PE enables highly efficient precise editing, resulting in a significant reduction of plasma low-density lipoprotein cholesterol and total cholesterol.ConclusionsOur innovative, modular system enhances flexibility, thus potentially facilitating the in vivo applicability of prime editing.
Gamma oscillations induced by 40-Hz visual-auditory stimulation for the treatment of acute-phase limb motor rehabilitation after stroke: study protocol for a prospective randomized controlled trial
Authors: Fu Wang , Yu Xiaoming , Lai Minghui , Li Yuanli , Yang Yingting , Qin Yong , Yu Min , Wang Feng , Wang Cong 
Published: April 2024

Abstract
Background
The incidence of hemiparetic limb dysfunction reaches 85% in stroke patients, emerging as a critical factor influencing their daily lives. However, the effectiveness of current rehabilitation treatments is considerably limited, particularly in patients with upper extremity impairment. This study aims to conduct a prospective clinical trial to validate the safety and effectiveness of gamma oscillations induced by 40-Hz visual-auditory stimulation in treating post-stroke upper limb dysfunction and to explore the relevant mechanisms.

Methods
This trial is a prospective, randomized controlled, double-blind study. All enrolled patients were randomly assigned to two groups. The experimental group received intervention through 40-Hz visual-auditory stimulation, while the control group underwent intervention with randomly matched visual-auditory stimulation frequencies. The primary efficacy endpoint is the change in motor function. Secondary efficacy endpoints include motor-evoked potentials, cerebral hemodynamic changes, neural network connectivity, and alterations in synaptic-related genes. Safety evaluation included major adverse events, all-cause mortality, and photosensitive epilepsy. Assessments will be conducted at baseline, after a 14-day treatment period, and during subsequent follow-up visits (at 3 and 6 months) post-treatment. The differences between the two groups will be compared.

Discussion
This study will evaluate the safety and efficacy of gamma oscillations induced by 40-Hz visual-auditory stimulation in treating patients with upper extremity dysfunction after an acute cerebral stroke. Concurrently, we will explore potential mechanisms, including changes in synaptic-related genes and neural network connectivity. This trial is expected to provide evidence for the effectiveness of this new technique in treating upper extremity dysfunction after a stroke and improving patients’ quality of life.

Trial registration
The study protocol has been registered with the Chinese Clinical Trial Registry (ChiCTR) under registration number ChiCTR2300076579 on October 12, 2023.
A Systematic review of the factors that affect soccer players’ short-passing ability—based on the Loughborough Soccer Passing Test
Authors: Wang Bihan , Wan Bin , Chen Shu , Zhang Yu , Bai Xiaorong , Xiao Wensheng , Tang Changfa , Long Bo 
Published: April 2024

Abstract
Objective
This study synthesizes evidence from the Loughborough Passing Test to evaluate the short-passing ability of soccer players and summarizes the reported variables that affect this ability to provide support for the development and improvement of short-passing abilities in soccer players.

Methods
In this systematic review using the PRISMA guidelines, a comprehensive search was conducted in Web of Science, PubMed, and EBSCOhost from inception to July 2023 to identify relevant articles from the accessible literature. Only studies that used the Loughborough test to assess athletes' short-passing ability were included. The quality of the included studies was independently assessed by two reviewers using the PEDro scale, and two authors independently completed the data extraction.

Results
Based on the type of intervention or influencing factor, ten studies investigated training, nine studies investigated fatigue, nine studies investigated supplement intake, and five studies investigated other factors.

Conclusion
Evidence indicates that fitness training, small-sided games training, and warm-up training have positive effects on athletes' short-passing ability, high-intensity special-position training and water intake have no discernible impact, mental and muscular exhaustion have a significantly negative effect, and the effect of nutritional ergogenic aid intake is not yet clear. Future research should examine more elements that can affect soccer players' short-passing ability.

Trial registration
https://inplasy.com/., identifier: INPLASY20237.
Pannexin 1 dysregulation in Duchenne muscular dystrophy and its exacerbation of dystrophic features in mdx mice
Authors: Freeman Emily , Langlois Stéphanie , Leyba Marcos F. , Ammar Tarek , Léger Zacharie , McMillan Hugh J. , Renaud Jean-Marc , Jasmin Bernard J. , Cowan Kyle N. 
Published: April 2024

Abstract
Background
Duchenne muscular dystrophy (DMD) is associated with impaired muscle regeneration, progressive muscle weakness, damage, and wasting. While the cause of DMD is an X-linked loss of function mutation in the gene encoding dystrophin, the exact mechanisms that perpetuate the disease progression are unknown. Our laboratory has demonstrated that pannexin 1 (Panx1 in rodents; PANX1 in humans) is critical for the development, strength, and regeneration of male skeletal muscle. In normal skeletal muscle, Panx1 is part of a multiprotein complex with dystrophin. We and others have previously shown that Panx1 levels and channel activity are dysregulated in various mouse models of DMD.

Methods
We utilized myoblast cell lines derived from DMD patients to assess PANX1 expression and function. To investigate how Panx1 dysregulation contributes to DMD, we generated a dystrophic (mdx) mouse model that lacks Panx1 (Panx1−/−/mdx). In depth characterization of this model included histological analysis, as well as locomotor, and physiological tests such as muscle force and grip strength assessments.

Results
Here, we demonstrate that PANX1 levels and channel function are reduced in patient-derived DMD myoblast cell lines. Panx1−/−/mdx mice have a significantly reduced lifespan, and decreased body weight due to lean mass loss. Their tibialis anterior were more affected than their soleus muscles and displayed reduced mass, myofiber loss, increased centrally nucleated myofibers, and a lower number of muscle stem cells compared to that of Panx1+/+/mdx mice. These detrimental effects were associated with muscle and locomotor functional impairments. In vitro, PANX1 overexpression in patient-derived DMD myoblasts improved their differentiation and fusion.

Conclusions
Collectively, our findings suggest that PANX1/Panx1 dysregulation in DMD exacerbates several aspects of the disease. Moreover, our results suggest a potential therapeutic benefit to increasing PANX1 levels in dystrophic muscles.
Feasibility of lactiplantibacillus plantarum postbiotics production in challenging media by different techniques
Authors: Khakpour Mahsa , Mohsenzadeh Mohammad , Salari Amir 
Published: April 2024

AbstractThe postbiotic derived from Lactiplantibacillus plantarum bacteria was produced in three culture media: milk, MRS, and whey, and its antibacterial and antifungal properties were evaluated. To investigate the production efficiency of postbiotics, three methods, heating, sonication and centrifugation, were utilized to prepare postbiotics in MRS broth culture medium. The antibacterial potency of the postbiotic was evaluated using the agar well-diffusion method, and MIC and MBC tests were conducted for different treatments. The results of the study showed that the postbiotic prepared in food environments such as milk and cheese whey can have antibacterial and antifungal properties similar to the postbiotic prepared in the MRS culture medium. However, it is possible to enrich food matrices such as milk and cheese whey and make further adjustments in terms of pH settings. Additionally, the thermal process was able to create a nanoscale postbiotic, which is a significant achievement for the application of postbiotics in the food and pharmaceutical industries. The future outlook of postbiotics clearly indicates that the emergence of this generation of probiotics can have an attractive and functional position in the food and pharmaceutical industries. Therefore, future research focusing on this subject will contribute to the development of this generation of postbiotics.