bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphofunctional Characteristics of Chinchilla lanigera Liver and Kidneys in the Setting of Hydrogen-Rich Water Regime
Authors: Panina E. V. , Karkischenko V. N. , Ostrenko K. S. , Petrov D. V. , Sorochan A. E.
Published: November 2024

The article presents the results of including hydrogen-rich water in the diet of Chinchilla lanigera (longtailed chinchilla). The experiment was carried out on two groups of chinchillas: control (n=10) and experimental (n=10). The long-term scientific experiment covered the period of three years. At the beginning, in to determine the toxic effects of molecular hydrogen. To that end, laboratory investigations were conducted to assess the morphometry of the renal capillary glomeruli, characterizing the vascular bed, and to determine the area of hepatocytes, their nuclear-cytoplasmic ratio, as well as the stromal and parenchymal components of the liver. The long-term use of hydrogen-rich water was shown to contribute to a decrease in the area of the renal glomeruli of animals in the experimental group by 27% (p<0.01). In addition, an increase in the parenchymal component of the liver and the volume of cytoplasm in hepatocytes (p<0.01) was observed. It is concluded that the inclusion of hydrogen-rich water in the diet of animals has a beneficial effect on the condition of the renal glomeruli and vascular system and has no toxic effect on the liver.
Integrating the Software Development Lifecycle into Work-Integrated Learning:
Authors: Mbele Mpho , Swart James Swart
Published: November 2024

Work-integrated learning is crucial for student development, providing hands-on experience in industry placements or project-based learning at higher educational institutions. This article evaluates the impact of adopting a Software Development Lifecycle (SDLC) process in work-integrated learning software development projects at a University of Technology. Comparing two student projects, the waterfall model resulted in substandard conversion between class diagrams and route classes, while the agile model allowed frequent reviews and modifications, resulting in alignment between class diagrams and route classes. The key difference was the absence of clear directional indicators and comprehensive descriptions of class relationships. It is recommended that students adopt an appropriate SDLC model that meets their specific project needs within a work-integrated learning environment.
Biomechanical analysis of stress distribution and failure risk in mandibular incisors restored with resin-bonded fixed partial dentures using CAD/CAM materials and restoration designs
Authors: Wang Hailiang , Cai Jingwen , Liang Jie , Wang Yong , Liu Yunsong
Published: November 2024

Background

Computer-aided design/manufacturing (CAD/CAM) materials are widely used in resin-bonded fixed partial dentures (RBFPDs), but their suitability across different designs has not been fully assessed. This study compares the stress distribution and failure probability of mandibular incisors restored by RBFPDs with various CAD/CAM materials.

Materials and methods

Finite-element models of single- and double-ended RBFPDs were created using cone-beam computed tomography (CBCT) data. Five CAD/CAM materials (IPS e.max CAD, IPS e.max ZirCAD, Vita Enamic, Lava Ultimate, Vitablocs MarkII) were tested under vertical and oblique (45°) loading with a 100 N force. Stress distribution and failure risk were evaluated for each material and design.

Results

Oblique loading produced the highest stress and displacement for single-ended RBFPDs. Lava Ultimate had the largest displacement and principal stress, while IPS e.max ZirCAD showed the highest equivalent stress. IPS e.max CAD exhibited the lowest displacement and principal stress among double-ended RBFPDs under oblique loading.

Conclusion

This study demonstrated that double-ended RBFPDs experience lower stress and strain compared to single-ended designs, particularly under oblique loading. Vita Enamic had the highest failure risk, while IPS e.max ZirCAD had the lowest. These insights into stress distribution and material performance offer valuable guidance for material selection and restoration design, aiming to improve the longevity and success of RBFPDs in mandibular incisor restorations.
The oral-gut microbiome axis in breast cancer: from basic research to therapeutic applications
Authors: Huang Lan , Jiang Chun , Yan Meina , Wan Weimin , Li Shuxiang , Xiang Ze , Wu Jian
Published: November 2024

As a complicated and heterogeneous condition, breast cancer (BC) has posed a tremendous public health challenge across the world. Recent studies have uncovered the crucial effect of human microbiota on various perspectives of health and disease, which include cancer. The oral-gut microbiome axis, particularly, have been implicated in the occurrence and development of colorectal cancer through their intricate interactions with host immune system and modulation of systemic inflammation. However, the research concerning the impact of oral-gut microbiome axis on BC remains scarce. This study focused on comprehensively reviewing and summarizing the latest ideas about the potential bidirectional relation of the gut with oral microbiota in BC, emphasizing their potential impact on tumorigenesis, treatment response, and overall patient outcomes. This review can reveal the prospect of tumor microecology and propose a novel viewpoint that the oral-gut microbiome axis can be a breakthrough point in future BC studies.
Beta-blockers after percutaneous coronary intervention for acute myocardial infarction and non-reduced left ventricular ejection fraction
Authors: Jeong Jun-Chang , Park Jong-Il , Kim Byung-Jun , Kim Hong-Ju , Choi Kang-Un , Nam Jong-Ho , Lee Chan-Hee , Son Jang-Won , Park Jong-Seon , Her Sung-Ho , Chang Ki-Yuk , Ahn Tae-Hoon , Jeong Myung-Ho , Rha Seung-Woon , Kim Hyo-Soo , Gwon Hyeon-Cheol , Seong In-Whan , Hwang Kyung-Kuk , Hur Seung-Ho , Cha Kwang-Soo , Oh Seok-Kyu , Chae Jei-Keon , Kim Ung
Published: November 2024

Background

Data on the clinical impact of beta-blockers (BBs) in patients with myocardial infarction (MI) who had non-reduced left ventricular ejection fraction (LVEF) after percutaneous coronary intervention are limited.

Methods

From 2016 to 2020, we evaluated a cohort of 12,101 myocardial infarction patients with a non-reduced LVEF (≥40%) from the Korean Acute Myocardial Infarction Registry V. Patients were divided into two groups based on their BB (carvedilol, bisoprolol, or nebivolol) treatment at discharge: with beta-blocker treatment (BB, n = 9,468) and without beta-blocker treatment (non-BB, n = 2,633). The primary endpoint after discharge was the occurrence of patient-oriented composite endpoints (POCEs), including all-cause mortality, any MI, or any revascularization at 1-year follow-up.

Results

The median follow-up period was 353 days (interquartile range, 198–378 days). At 1-year follow-up, no significant differences were observed in the primary endpoint between the BB group and the non-BB group. Before propensity score (PS) matching, the POCE incidence was 3.1% in the BB group vs. 3.4% in the non-BB group [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.68–1.09, p = 0.225]. After PS matching, the POCE incidence remained similar between the two groups (3.7% vs. 3.4%, HR 1.01, 95% CI 0.76–1.35, p = 0.931). Individual outcomes, including all-cause mortality, myocardial infarction, and revascularization, also showed no significant differences between the two groups. Independent predictors of 1-year POCEs after discharge were age, chronic kidney disease, reduced LVEF, and multivessel disease.

Conclusion

BB treatment in patients with acute MI and non-reduced LVEF was not associated with a significant reduction in cardiovascular outcomes at 1-year follow-up.
Comparison of clinical outcomes of drug-coated balloons angioplasty vs. plain old balloons angioplasty for peripheral arterial disease: an umbrella meta-analysis
Authors: Li Jiacheng , Lu Wei , Lin Lihong , Wu Jiawen , Cheng Guobing , Hu Qiang , Guo Yi
Published: November 2024

Background

Peripheral artery disease (PAD) affects millions globally, causing significant morbidity. Traditional treatments like plain old balloon angioplasty (POBA) have limited success due to high restenosis rates. Drug-coated balloon angioplasty (DCBA) has emerged as a promising alternative, locally delivering antiproliferative drugs like paclitaxel to reduce restenosis. However, the clinical outcomes of DCBA compared to POBA remain inconsistent across various studies.

Objective

This umbrella meta-analysis aimed to compare the clinical outcomes of DCBA and POBA in PAD patients, synthesizing data from multiple meta-analyses to provide a more robust evidence base.

Methods

We conducted an umbrella meta-analysis following PRISMA guidelines, systematically reviewing Cochrane Library, Embase, PubMed, and Web of Science. Studies were included if they compared DCBA and POBA in PAD patients, focusing on primary outcomes such as target lesion revascularization (TLR), primary patency (PP), all-cause mortality (ACM), and amputation. Secondary outcomes included restenosis, late lumen loss (LLL), and major adverse events (MAE).

Results

Sixteen meta-analyses were included. DCBA significantly reduced the risk of TLR (OR: 0.41, 95% CI: 0.34–0.49), PP was significantly higher in DCBA (OR: 2.05, 95% CI: 1.53–2.75), and restenosis was lower (OR: 0.46, 95% CI: 0.41–0.51). No significant differences were found in ACM or amputation risk between the two groups. Heterogeneity was moderate to high across most outcomes.

Conclusion

DCBA provides significant advantages over POBA in reducing TLR and restenosis while maintaining vessel patency. However, the effects on ACM and amputation remain inconclusive. Future research should focus on long-term safety and identifying which patient subgroups benefit most from DCBA.

Systematic Review Registration

https://www.crd.york.ac.uk/, PROSPERO [CRD42024591967].
Research on microseismic source location based on time quality constraints
Authors: Wu Xuefei , Xie Qian , Yan Junsheng
Published: November 2024

Introduction

To develop a small-scale regional microseismic location model for coal mines and enhance the accuracy of microseismic location at the bottom plate,this article proposes a high-precision location algorithm for 3D-Fast Sweeping Method (3D-FSM) seismic sources under time quality constraints.

Methods

The study investigates the numerical simulation of microseismic location accuracy on coal seam floor, considering various observation systems, arrival time picking errors, and wave velocity discrepancies. The algorithm employs a VGG-16 deep learning network to train and establish a quality control model for P-wave pickup values; Next, utilizing the 3D-FSM framework, it calculate the seismic wave travel time field and applies Fermat’s principle for each detection point, as well as the reversible principle of elastic wave propagation path. This allows for the determination of the spatial path and travel time from any potential source point to the detection point. Finally, the algorithm scans each computational node, using the controlled travel time difference to identify the source point corresponding to the smallest spatial node.

Results

The results indicate that the location error of the borehole tunnel observation system is smaller than that of the tunnel observation system. Specifically, with the borehole tunnel observation system, the variance in P-wave arrival time picking is 1 ms, and the wave velocity variance is 20 m/s2, demonstrating high accuracy.

Discussion

The findings suggest that the 3D-FSM seismic source location algorithm, under quality control, approaches the precision of manual location methods and exhibits high reliability, even when disregarding significant accuracy errors during the quality control location process.
Frequency-broadening method of seismic data based on sparse reconstruction inversion strategy
Authors: Liu Shiyou , Song Weiqi , Yan Anju , Huang Sheng
Published: November 2024

To broaden the effective frequency bandwidth of seismic data and enhance its resolution, we investigate the high-resolution reconstruction method grounded in compressed sensing sparse theory, utilizing the characteristics of sparse decomposition of seismic signals. First, we examine the construction of an over-complete dictionary, which is then employed to sparsely represent the seismic data and derive the reflection coefficient, combined with noise, forms a mixed sparse component. By removing the noise sparse component from this mixture, we isolate a clean reflection coefficient. In the iterative reconstruction process of compressed sensing sparse decomposition, weak signal can easily be overwhelmed by the application of the maximum energy principle. To address this issue, we propose a useful signal control retention method incorporating lateral adjacent low-rank constraints. This approach increases the probability of optimizing weak signal dictionary atoms, mitigates the unbalanced reconstruction of strong and weak signals, and facilitates the comprehensive reconstruction of both signal types. Ensuring reconstruction accuracy is crucial, as the conditions for reconstruction significantly affect reliability. Therefore, we employ a signal-to-noise ratio estimation method to establish an adaptive iteration stop condition based on a residual threshold. During each iteration, the signal-to-noise ratio is recalculated, and the signal-to-noise ratio is multiplied by the residual to produce a weight residual. Finally, this new residual is used in the inner product calculations, allowing for the preferential selection of dictionary atoms. Both theoretical models and actual data validate the rationality and effectiveness of the proposed method. Analysis of real data demonstrates that our approach significantly enhances the seismic frequency band width and markedly improves the resolution of seismic data.
Drought responses and adaptation in plants differing in life-form
Authors: Nour Mudawi M. , Aljabi Hanadi Riyad , AL-Huqail Arwa Abdulkreem , Horneburg Bernd , Mohammed Afrah E. , Alotaibi Modhi O.
Published: November 2024

Drought is considered one of the most critical abiotic environmental stresses and limits plant growth, development, and productivity. It constitutes a real threat to humanity, especially in dry areas worldwide. Plants manage the negative effects of drought through a complex set of related mechanisms. Knowledge of plant responses and adaptation is more meaningful in plant breeding and genetics for improving drought resistance species. This review will focus on drought response mechanisms and drought adaptation, providing examples from plant species differing in their life-form, including herbaceous and woody plants. Additionally, the potential role of enhancing plant drought responses will be emphasized. This review is of potential significance to researchers and those who wish to obtain a glimpse into plant behavior under drought conditions.
Exploring causal associations between interleukins, their receptors, and acute respiratory distress syndrome: a bidirectional-Mendelian Randomization study
Authors: Ma Jia-wei , Tang Ji-chun , Fang Hong-zhi
Published: November 2024

Background

Acute Respiratory Distress Syndrome (ARDS) is a severe lung condition posing significant health risks. Observational studies have indicated a potential linkage between ARDS and various interleukins, such as Interleukin-8, −2, −6, and −1β. However, the causal relationships between specific interleukins, their receptors, and ARDS remain unclear.

Methods

This study employed bidirectional Mendelian Randomization (MR) to investigate the causal associations between 197 different interleukins, interleukin receptors, and ARDS. GWAS summary data for interleukins and their receptors were sourced from publicly available studies, while ARDS data were derived from the FinnGen database. Wald Ratio and Inverse Variance Weighted (IVW) methods were primarily utilized in the MR analyses. Reverse MR was also conducted to explore reverse causations.

Results

The study identified significant causal relationships between several interleukins, their receptors and ARDS. Specifically, Interleukin-17 receptor D (IL-17RD) (OR = 0.67, 95%CI = 0.51–0.89, p = 0.006), Interleukin-22 receptor subunit alpha-1 (IL22RA-1) (OR = 1.45, 95%CI = 1.08–1.96, p = 0.014), Interleukin-20 receptor subunit alpha (IL20RA) (OR = 0.53, 95%CI = 0.32–0.89, p = 0.016), Interleukin-22 (IL-22) (OR = 3.60, 95%CI = 1.20–10.83, p = 0.022), Interleukin-23 receptor (IL-23R) (OR = 2.14, 95%CI = 1.10–4.17, p = 0.025), Single Ig IL-1-related receptor (SIGIRR) (OR = 1.22, 95%CI = 1.00–1.48, p = 0.047) showed notable associations with ARDS. No reverse causal relationships were found on results above, and neither heterogeneity nor pleiotropy was detected in the analysis.

Conclusion

This study elucidates the causal connections between specific interleukins, their receptors and ARDS, contributing significantly to the understanding of ARDS pathogenesis. These findings offer a foundation for further research and potential therapeutic interventions targeting these interleukins and receptors in ARDS management. The absence of reverse causation and pleiotropy, heterogeneity reinforces the robustness of these associations.
Women's empowerment and current contraceptive use in Pakistan: informed by theory of gender and power
Authors: Kumari Bhavita , Do Mai , Madkour Aubrey Spriggs , Wisniewski Janna Marie
Published: November 2024

Introduction

It is evident from the stagnant modern contraceptive rate and the growing population of Pakistan that the family planning (FP) programs in Pakistan have failed to deliver successfully. The study examines the association of domains of women's empowerment, following the Theory of Gender and Power, with the current use of contraceptive methods and how intimate partner violence (IPV) can moderate such associations in Pakistan.

Methods

Married women of reproductive age from the Pakistan DHS (2017–18) were included in the analysis (n = 14,502). Key independent variables were identified using Connell's Theory of Gender and Power operationalized by Wingood and DiClemente, and constructs were created using principal component analysis. Multinomial logistic regressions were conducted to assess the relationships of the three empowerment divisions (i.e., sexual division of labor, sexual division of power, and cathexis), to the current use of contraceptives.

Results

When all empowerment domains were included in the model along with covariates, education (sexual division of labor), sex negotiations (sexual division of power), and husband's fertility intentions (cathexis) remained significant in their associations with modern contraceptive use.

Conclusion

This is the first study in Pakistan to examine multi-faceted empowerment, applying Connell's theory of gender and power to identify key domains associated with contraceptive use. A multi-prong approach to FP programs that aims to improve specific domains of women's empowerment and to increase FP service use may be more likely to succeed than stand-alone programs.
Dietary seaweed extract mitigates oxidative stress in Nile tilapia by modulating inflammatory response and gut microbiota
Authors: Siddik Muhammad A. B. , Francis Prue , Foysal Md Javed , Francis David S.
Published: November 2024

Introduction

Extreme water temperature affects the well-being of all aquatic animals, including fish. Higher temperatures can lead to the generation of reactive oxygen species (ROS), which can induce oxidative stress and negatively impact fish health and well-being. This study investigated the protective effects of seaweed extract on growth, antioxidant status, inflammatory responses, and gut microbiota to gain a better understanding of the acclimatization ability of Nile tilapia, Oreochromis niloticus in response to oxidative stress caused by high water temperatures.

Methods

Red-seaweed, Gracilaria tenuistipitata rich in polyphenols (i.e., total phenolics and flavonoids content) was considered for the preparation of the Gracilaria extract (GE) for the study. Nile tilapia were fed the GE supplemented diet along with a control diet for 42 days, followed by 14 days of temperature ramping at a rate of 1°C every two days to the desired target (35°C) and 14 days of holding at 32°C for acclimatation.

Results

Nile tilapia fed the GE had a significantly higher growth performance attributed to increased muscle fiber size compared to control (p < 0.05) after the 70 days of feeding trial. Fish fed the GE diet also showed a significantly lower lipid peroxidation by decreased malondialdehyde level when compared to control (p < 0.05). Furthermore, GE diet exhibited increased red blood cell counts with the decreased number of cellular and nuclear abnormalities. The gene expression of tight junction (i.e., occludin, claudin1, ZO-1) and nrf2 (antioxidant biomarker) were upregulated, while hsp70 (related to stress response) was downregulated in fish fed the GE diet. Additionally, GE supplementation led to an increase in bacterial diversity and the abundance of phylum Firmicutes, order Lactobacillales, and genera Sphingobacterium and Prevotella in the distal gut of Nile tilapia, which are mostly considered as beneficial for fish.

Conclusion

The findings suggest that GE has the potential to be used as a dietary supplement to improve health, particularly as a stress-resistant supplement in the diet for Nile tilapia. This study may help make more informed decisions for tailoring the nutrient requirements of fish in the face of climate warming.
A new and promising C-phycocyanin-producing cyanobacterial strain, Cyanobium sp. MMK01: practical strategy towards developing a methodology to achieve C-phycocyanin with ultra-high purity
Authors: Shafiei Melika , Shafiei Maral , Mohseni Sani Naeema , Guo Wangbiao , Guo Shuaiqi , Vali Hojatollah , Akbari Noghabi Kambiz
Published: November 2024

Selecting a suitable cyanobacterial strain and developing easy-to-afford purification processes are two crucial aspects impacting the optimal production yield and appropriate purity of C-phycocyanin (C-PC). Cyanobium sp. MMK01, a highly efficient C-PC-producing bacterium, was identified among four cyanobacterial isolates using morphological characteristics and 16S rRNA gene sequencing. The purification process of C-PC began with ammonium sulfate precipitation, leading to a purity index (PI) of 4.04. Subsequent purification through ion exchange chromatography ultimately resulted in an ultra-highly purified form of C-PC with a significant PI of 5.82. SDS-PAGE analysis of purified C-PC showed the presence of two distinct bands, α (13 kDa) and β (15 kDa). Significantly effective at scavenging free radicals, C-PC also inhibits the viability of human lung cancer cells (Calu-6). Antibacterial, anti-inflammatory, antioxidant, and cancer-preventive compounds were detected in the MMK01 cells’ methanolic extract following GC–MS analysis. The promising results indicate that Cyanobium sp. MMK01 has a great deal of potential for producing C-PC that is on par with strains found in the market, and the tried-and-true two-step purification process proved to work well to achieve an ultra-highly purified form of C-PC.
Allopregnanolone and mood in the peripartum: a longitudinal assessment in healthy women
Authors: Grötsch Maria Katharina , Ehlert Ulrike
Published: November 2024

Background

Allopregnanolone (ALLO), a neuroactive steroid hormone derived from progesterone, can modulate mood via the GABA-A receptor. Peripartum mood can be influenced by psychosocial factors, previous mental illness, and hormonal changes. Studies suggest a U-shaped effect of ALLO on mood, with some women being more sensitive to hormonal changes than others. However, research in the peripartum is inconclusive.

Methods

This study explored the link between salivary ALLO and mood during the peripartum. Over 12 weeks, N = 61 women completed the Edinburgh Postnatal Depression Scale and the State Anxiety subscale from the State–Trait Anxiety Inventory and provided saliva samples. Salivary ALLO was analyzed using an enzyme-linked immunosorbent assay, validated for saliva samples. Group-based trajectory modeling was performed to identify trajectories of ALLO courses. Multinomial logistic regression models were employed to identify risk factors associated with these trajectories.

Results

ALLO levels increased during pregnancy and dropped 2 weeks before delivery. Three different trajectory groups of ALLO courses emerged (high decreasing, low moderate, low reduced). Trajectory groups were associated with distinct psychological risk factors, including previous mental illness, adverse childhood experiences, sleep problems, premenstrual symptoms, and resilience. The peripartum ALLO course showed a negative linear association with anxiety symptoms and a U-shaped association with depressive symptoms.

Discussion

The consideration of individual ALLO courses can predict the risk for peripartum mood symptoms, particularly among women with preexisting risk factors. While the majority of women remain healthy during the peripartum transition, analyzing ALLO subgroups helps to provide a better understanding of the relationship between ALLO and peripartum mood.
SARS-CoV-2 Nsp7 plays a role in cognitive dysfunction by impairing synaptic plasticity
Authors: Guo Jiazheng , Li WeiLing , Huang Mengbing , Qiao Jialu , Wan Pin , Yao Yulin , Ye Lirui , Ding Ye , Wang Jianing , Peng Qian , Liu Wei , Xia Yiyuan , Shu Xiji , Sun Binlian
Published: November 2024

It has been reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in long-term neurological symptoms such as cognitive dysfunction, however the specific mechanisms underlying this phenomenon remain unclear. Initially, we confirmed a reduction in the level of synaptic proteins in SH-SY5Y neurons following SARS-CoV-2 infection. SARS-CoV-2 Nsps are crucial for the efficient replication of the virus and play important roles in the interaction between virus and host cell. Nsps screening experiments implied that Nsp7 is able to reduce the level of synapsin-1. Furthermore, overexpression of Nsp7 in SH-SY5Y cells and mouse primary neurons demonstrated that Nsp7 could decrease the levels of synaptic proteins without affecting neuronal viability. Moreover, C57BL/6 mice receiving AAV-GFP-Nsp7 injections into the ventral hippocampus displayed impaired memory ability, along with reduced dendritic spine density and synaptic protein levels. Mechanistic investigations suggested that Nsp7-induced mitochondrial damage led to ROS production and ATP levels decreasing in neurons. Additional experiments employing the ROS inhibitor NAC demonstrated that Nsp7 suppressed the expression of synaptic proteins via ROS inducing, implicating mitochondrial dysfunction in synaptic plasticity impairment and subsequent cognitive dysfunction. Our findings underscore the crucial role of SARS-CoV-2 Nsp7 in cognitive dysfunction, which is potentially mediated through impaired synaptic plasticity via mitochondrial damage. This study enhances our understanding of the pathogenic mechanisms underlying central nervous system-related symptoms associated with SARS-CoV-2 infection.
A phase II study evaluating safety and efficacy of niraparib in patients with previously treated homologous recombination defective metastatic esophageal/gastroesophageal junction/proximal gastric adenocarcinoma
Authors: Khalid Ahmed Bilal , Fountzilas Christos , Burney Heather N. , Mamdani Hirva , Schneider Bryan P. , Fausel Christopher , Perkins Susan M. , Jalal Shadia
Published: November 2024

Introduction

Esophageal adenocarcinoma (EAC) remains a devastating disease and second line treatment options in the metastatic space are limited. Homologous recombination (HR) defects have been described in EAC in up to 40% of patients. Poly (ADP-ribose) polymerase (PARP)1 and PARP2 inhibitors have shown efficacy in HR defective prostate and ovarian cancers. Here, we describe the activity of the PARP inhibitor niraparib in metastatic EAC with HR defects.

Methods

In this single arm Simon two-stage Phase II study, we assessed the safety and efficacy of niraparib in patients with metastatic EAC previously treated with platinum containing chemotherapy harboring defective HR. Defective HR was defined as deleterious alterations in the following HR genes: BRCA1/2, PALB2, ATM, BARD1, BRIP1, CDK12, CHEK2, FANCA, RAD51, RAD51B, RAD51C, RAD51D, RAD54L, NBN, ARID1A and GEN1.

Results

14 patients were enrolled in this study. The trial was stopped early due to slow accrual. 3 patients did not have post-treatment scans because of rapid clinical decline. The overall response rate (ORR) (95% exact CI) was 0/11 = 0% (0%, 28.49%). The disease control rate (DCR) (95% exact CI) was 2/11 = 18.2% (2.3%, 51.8%). The median PFS was 1.8 months (95% CI = 1.0-3.7). The median OS for evaluable patients was 6.6 months (95% CI =2.7-11.4) and 5.7 months for all patients (95% CI =2.7-10.1). The most common adverse events seen were anemia, fatigue, and thrombocytopenia.

Conclusion

In patients with metastatic EAC, single agent niraparib as second line therapy is not an effective option.
Efficacy and safety of anti-angiogenic drugs combined with chemotherapy in the treatment of platinum-sensitive/resistant ovarian cancer: a meta-analysis with trial sequential analysis of randomized controlled trials
Authors: He Haining , Zhou Fei
Published: November 2024

Background

With the emergence of new anti-angiogenic treatments and the ongoing updates to clinical guidelines, the effectiveness and safety of these agents in treating platinum-sensitive/resistant ovarian cancer (OC) are yet to be fully determined. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of anti-angiogenic drugs combined with chemotherapy (CT) for platinum-sensitive OC (PSOC) or platinum-resistant OC (PROC).

Methods

A comprehensive literature search was conducted across several databases, including PubMed, Web of Science, Embase, and the Cochrane Library, encompassing all pertinent randomized controlled trials (RCTs) up to 31 May 2024. The primary outcomes for the meta-analysis were progression-free survival (PFS) and overall survival (OS), while the objective response rate (ORR), adverse events (AEs) of any grade, and grade ≥3 AEs were considered secondary endpoints. Data synthesis involved the computation of hazard ratio (HR), relative risk (RR), along with their 95% confidence interval (CI) and prediction interval (PI). Trial sequential analysis was carried out using STATA 12.0, R software 4.3.1, and TSA v0.9.5.10 Beta software.

Results

This meta-analysis encompassed 15 RCTs. The overall analysis revealed that compared to CT alone (or plus placebo), anti-angiogenic drugs combined with CT significantly improved PFS (HR [95% CI] = 0.573 [0.518–0.633], 95% PI: 0.383-0.876) and ORR (RR [95% CI] = 1.362 [1.260–1.472], 95% PI: 0.824–2.251), but also increased the incidence of grade ≥3 AEs (RR [95% CI] = 1.115 [1.070–1.162], 95% PI: 0.870–1.422) in PSOC patients. For PROC patients, this combination therapy notably improved PFS (HR [95% CI] = 0.542 [0.475–0.619], 95% PI: 0.322–0.930), OS (HR [95% CI] = 0.752 [0.646–0.875], 95% PI: 0.554-0.997), and ORR (RR [95% CI] = 2.141 [1.702–2.694], 95% PI: 0.839–5.307), whilst simultaneously elevating the risk of grade ≥3 AEs (RR [95% CI] = 1.487 [1.216–1.819], 95% PI: 0.755–2.828).

Conclusion

Our research verified the advantages of combining anti-angiogenic agents with CT in enhancing PFS and ORR for patients with PSOC, and also confirmed improvements in PFS, OS, and ORR for those with PROC. It is crucial for medical practitioners to remain alert to the potential occurrence of AEs when implementing this combined therapeutic approach in a clinical milieu.

Systematic Review Registration:

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024552010.
Effects of administering berberine alone or in combination on type 2 diabetes mellitus: a systematic review and meta-analysis
Authors: Wang Jiacheng , Bi Chenhao , Xi Hongbin , Wei Fengqin
Published: November 2024

Background

Despite the availability of multiple therapies for Type 2 diabetes mellitus (T2DM), challenges remain due to side effects and efficacy limitations. Berberine (BBR) has shown broad anti-diabetic effects, prompting a systematic assessment of its efficacy and safety through a meta-analysis.

Methods

A comprehensive search was conducted across eight database and search engines from inception until 06/09/2024. Only randomized controlled trials (RCTs) meeting inclusion criteria were analyzed. The Cochrane risk of bias assessment tool and Jadad scale were used to evaluate study quality. Meta-analysis was performed using RevMan v5.3 and Stata/SE v15.1.

Results

Fifty studies involving 4,150 participants were included. BBR alone significantly reduced fasting plasma glucose (FPG) (MD = −0.59 mmol/L, p = 0.048), 2-h postprandial blood glucose (2hPBG) (MD = −1.57 mmol/L, p < 0.01), low-density lipoprotein cholesterol (LDL-C) (MD = −0.30 mmol/L, p < 0.01), total cholesterol (TC) (MD = −0.30 mmol/L, p = 0.034), and triglycerides (TG) (MD = −0.35 mmol/L, p < 0.01). When combined with hypoglycemic drugs, BBR significantly improved FPG (MD = −0.99 mmol/L, p < 0.01), 2hPBG (MD = −1.07 mmol/L, p < 0.01), glycated hemoglobin (HbA1c) (MD = −0.69%, p < 0.01), and other metabolic markers, including fasting insulin (Fins), homeostasis model assessment index for assessing insulin resistance (HOMA-IR), lipid profiles and inflammatory markers. The most common BBR dosage was 0.9–1.5 g/d, with treatment cycles typically lasting 1–3 months.

Conclusion

Current evidence suggests that BBR alone or in combination has significant potential for treating type 2 diabetes mellitus (T2DM). Future research should encompass a broader scope, including not just the beneficial effects of BBR in head-to-head studies, but more crucially, delving into its mechanisms of action with hypoglycemic drugs to optimize T2DM treatment strategies.
Identification, screening, and comprehensive evaluation of novel thrombin inhibitory peptides from the hirudo produced using pepsin
Authors: Chai Xiaoyu , Pan Fulu , Wang Qianqian , Wang Xinyu , Li Xueyan , Qi Dongying , Yi Zirong , Liu Huan , Zhang Jing , Zhang Yiming , Pan Yanli , Liu Yang , Wang Guopeng
Published: November 2024

Purpose

The inhibition of thrombin has proven to be an efficacious therapeutic approach for managing cardiovascular disease (CVD), with widespread implementation in clinical settings. Oral ingestion of peptides and protein drugs is influenced by gastrointestinal digestive enzymes. We aimed to evaluate the thrombin inhibitory properties of hirudo hydrolysates (HHS) produced by pepsin and propose a comprehensive approach to screen and evaluate thrombin inhibitors.

Methods

We evaluated the in vitro inhibitory properties of the hirudo extract, both before and after hydrolysis with pepsin, toward thrombin. We screened for the most potent thrombin inhibitory peptide (TIP) using nano liquid chromatography-tandem mass spectrometry (Nano LC-MS/MS) coupled with in silico analysis. Next, we employed the thrombin inhibition activity IC50 to investigate the interaction between TIP and thrombin, and conducted in vitro evaluations of its anticoagulant effects (APTT, TT, PT), as well as its ability to inhibit platelet aggregation. Furthermore, we utilized UV-Vis spectroscopy to explore structural changes in thrombin upon binding with TIP and employed molecular dynamics simulations to delve deeper into the potential atomic-level interaction modes between thrombin and TIP.

Results

The retention rate of thrombin inhibition for HHS was found to be between 60% and 75%. A total of 90 peptides from the HHS were identified using LC-MS/MS combined with de novo sequencing. Asn-Asp-Leu-Trp-Asp-Gln-Gly-Leu-Val-Ser-Gln-Asp-Leu (NDLWDQGLVSQDL, P1) was identified as the most potent thrombin inhibitory peptide after in silico screening (molecular docking and ADMET). Then, the in vitro study revealed that P1 had a high inhibitory effect on thrombin (IC50: 2,425.5 ± 109.7 μM). P1 exhibited a dose-dependent prolongation of the thrombin time (TT) and a reduction in platelet aggregation rate. Both UV-Vis spectroscopy and molecular dynamics simulations demonstrated that P1 binds effectively to thrombin.

Conclusion

Overall, the results suggested that HHS provides new insights for searching and evaluating potential antithrombotic compounds. The obtained P1 can be structurally optimized for in-depth evaluation in animal and cellular experiments.
Evaluation of the inhibitory mechanism of Pennisetum glaucum (pearl millet) bioactive compounds for rheumatoid arthritis: an in vitro and computational approach
Authors: Sharif Maria , John Peter , Bhatti Attya , Paracha Rehan Zafar , Majeed Abid
Published: November 2024

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial infiltration and pannus formation, and its rising incidence is significantly contributing to the global disability rate. Despite advances in biological drugs, no treatment has successfully cured or averted its progression. Consequently, natural drugs are being explored as alternative therapeutic strategies.

Objective

This study aims to evaluate the therapeutic potential of Pennisetum glaucum (pearl millet) and to identify its bioactive compounds to assess their effectiveness against RA targets.

Methods

The therapeutic potential of P. glaucum extracts was evaluated by antioxidant and anti-inflammatory assays. Gas chromatography-mass spectrometry (GC-MS) was utilized to identify the compounds in P. glaucum extract. The pharmacokinetics and safety profile of these compounds were studied by absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis. Network pharmacology, molecular docking, and molecular dynamic (MD) simulation were employed to identify the active compounds and their therapeutic targets in P. glaucum for RA treatment.

Results

Acidified methanol (AM) extract of P. glaucum showed the highest phenolic (213 ± 0.008 mg GAE/g DW) and flavonoid content (138.1 ± 0.03 mg RE/g DW), demonstrating significant antioxidant and anti-inflammatory potential. GC-MS of AM extract identified 223 compounds. Lipinski and toxicity parameters screened out 17 compounds. Protein–protein interaction (PPI) analysis shortlisted 20 key targets in RA pathways, nine of which were upregulated in five microarray datasets. Molecular docking and MD simulations revealed that compound-7 (benzenesulfonamide, 2-nitro-N-phenyl-) and compound-9 (Pregnane-3,20-diamine, (3.beta.,5.alpha.,20S)-) bind strongly with MMP9, JAK2, PTGS2, and HIF1a compared to the reference, predicting stable interaction with these upregulated genes. Finally, PASS (prediction of activity spectra for biological active substances) analysis further validated the anti-arthritic potential of these compounds based on their chemical structure.

Conclusion

This study uncovered a therapeutic drug candidate against HIF1a, MMP9, JAK2, and PTGS2 for RA from P. glaucum active compounds, laying the groundwork for future research.
Response of Salvia officinalis to zinc and silicon nanoparticles and pollen extract as alternates to traditional fertilizers
Authors: El-Mahrouk El-Sayed Mohamed , Atef Ekramy Abdel-Moatamed , Gabr Mohamed Kadry , Aly Mahmoud Ahmed , Mohamed Abdallah E. , Eisa Eman Abdelhakim , Gururani Mayank Anand
Published: November 2024

Salvia officinalis is used in a variety of medicinal and aromatic products. The effects of various treatments on sage (Salvia officinalis) plants were investigated in an open-field experiment conducted between 2021 and 2022. During the experiment, ZnO nanoparticles (NPs) were used at concentrations of 1.0 and 1.5 g/L, SiO2 NPs were used at concentrations of 0.1 and 0.2 g/L, and date palm pollen extracts (DPE) were used at concentrations of 15 and 25 g/L, in combination with NPK fertilizers at 75%, 50%, and 25%, respectively, with a control group of 100% NPK fertilizer. A treatment consisting of 75% NPK, 15 g/L DPE, 1.0 g/L ZnO NPs, and 0.1 g/L SiO2 NPs significantly improved vegetative traits and essential oil yield. Compared to the control in the growing seasons of 2021 and 2022, this treatment resulted in increases in plant height, chlorophyll index, fresh and dry weights, and essential oil yield (EOY) per plant of 23.40% and 28.30%, 27.56% and 26.54%, 42.17% and 42.95%, 64.10% and 62.79%, and 93.38% and 91.08%, respectively. Combinations of 25% NPK + 25 g/L DPE + 1.5 g/L ZnO nanoparticles + 0.2 g/L SiO2 NPs and 75% NPK + 0.1 g/L SiO2 NPs produced the highest essential oil percentage (EO%). During the experimental seasons, these treatments increased EO% by 15.45% and 26.25%. In total, 58 substances were identified across the different treatments in the essential oil composition analysis. There were 11 compounds in the 25% NPK, 25 g/L DPE, 1.5 g/L ZnO NPs, and 0.2 g/L SiO2 NPs treatments, and 32 in the 50% NPK, 25 g/L DPE, and 0.2 g/L SiO2 NPs treatments. Oxygenated hydrocarbons, sesquiterpenes, and monoterpenes varied by application. Thujone, camphor, manool, and ledol were the major constituents of the EO. Leaf chemical composition, antioxidant activity, and total phenolic compounds were significantly influenced by the treatments. In combination with DPE, ZnO and SiO2 NPs reduced the need for higher amounts of mineral NPK fertilizers. These agents can therefore be useful for advancing sustainable agricultural practices in novel and advantageous ways.
Understanding the impact of introduction of Robinia pseudoacacia on community functional structure and moisture regulation in the Loess Plateau, China, using a trait-based approach
Authors: Zheng Cheng , Yuan Liuhuan , Shi Haijing , Duan Gaohui , Liu Yangyang , Wen Zhongming
Published: November 2024

Depending on specific environmental conditions, Robinia pseudoacacia plantations can have a positive or negative impact on ecosystem function. Numerous studies have demonstrated that R. pseudoacacia plantations on the Loess Plateau has decreased the water levels in this area, increasing the risks of water resource security. Understanding the ecosystem function of the R. pseudoacacia plantations is thought to be critical to vegetation restoration in the Loess Plateau. However, no consensus exists on the mechanism by which afforestation affects moisture regulation under varying environmental conditions nor on how to manage R. pseudoacacia plantations to maintain the ecosystem function. In this study, we used the response–effect trait approach to examine the evolving relationship between community functional composition and water regulation by collecting community samples from R. pseudoacacia plantations and natural ecosystems across three vegetation zones (steppe, forest–steppe, and forest). Our goal was to clarify how the afforestation of R. pseudoacacia impacts functional composition and, consequently, moisture regulation. The findings indicated that R. pseudoacacia negatively impacts community structure and moisture regulation in the drier steppe and forest-steppe (P<0.05). Afforestation of R. pseudoacacia increases specific leaf area (SLA), leaf nitrogen content (LNC), and plant height (H), while weakening the trait correlations within the community, which is the main cause of the negative effect. Furthermore, we discovered that response and effect traits overlapped (leaf tissue density, LTD) in natural ecosystems but not in afforested ecosystems within the response–effect traits framework. In conclusion, our findings indicated that the functional structure of communities and moisture regulation are impacted R. pseudoacacia plantations in drier habitats. Additionally, because response–effect traits do not overlap and trait coordination declines, afforestation increases instability in the moisture regulation maintenance. The introduction of R. pseudoacacia weakens the coordination and coupling relationships between traits. We advise giving preference to native species over R. pseudoacacia for restoration in the dry steppe and forest-steppe zones. Trait-based restoration approaches can enhance the efficacy of restoration measure in achieving desired ecosystem functions.
A new critical methodology of cosmopoliticization
Authors: Klinke Andreas
Published: November 2024

A critical methodology of cosmopoliticization describes a new theoretically guided approach of empirical analysis to capture phenomena and quality of cosmopoliticization. The study and interpretation of cosmopoliticization and cosmopolitanism needs a critical pivot that draws on empirical issues and social facts to some extent to advance the theorizing of notions of cosmopolitan governance and democracy. First, I substantiate the rationale behind a new critical methodology of cosmopoliticization. Then, I argue that the sources of real-world insights of cosmopolitan practices and experiences can be derived from empirical analyses of three major subject matters, namely the formation of cosmopolitan solidarity, ethos, and belief, the role of cosmopolitan public spheres, and international democratization through civil society participation and deliberation. These analytical categories and units can convey cosmopolitan values and principles that are critical of a significant cosmopolitan departure from dominant nation-state related paradigms and politics because they embody an impetus for recognition and esteem of the ecological and ethical value and meaningfulness of the entire earth system for humankind in terms of a right conduct and practice in present and future.
Sexual violence and rape among young migrants in Sweden: a cross-sectional study on prevalence, determinants, perpetrators, and reporting patterns
Authors: Baroudi Mazen , Nkulu Kalengayi Faustine Kyungu
Published: November 2024

Background

Young migrants are particularly vulnerable to SV (SV) due to their age and the challenges of migration. However, there is limited knowledge regarding SV among young migrants in Sweden. This study aims to assess the prevalence, determinants, perpetrators, and reporting patterns of SV and rape.

Methods

We analyzed data from the 2018 survey on migrants’ sexual and reproductive health and rights, involving 1773 migrants aged 16–29. We estimated prevalence rates and calculated crude and adjusted prevalence ratios (APR) with 95% confidence intervals (CI) using descriptive and log-binomial regression analyses.

Results

The overall prevalence of SV was 25.1%, with rape at 9%. Higher SV prevalence were reported by non-binary individuals (APR: 2.60, CI: 1.54 to 4.38), Lesbian, Gay, Bisexual and Asexual (LGBA) individuals (APR: 1.56, CI: 1.22 to 2.01), those with 10–12 years (APR: 1.35, CI: 1.04 to 1.74) and over 12 years of education (APR: 1.61, CI: 1.23 to 2.11), and migrants awaiting asylum decisions (APR: 1.67, CI: 1.25 to 2.23). Rape prevalence was higher among those born in non-conflict settings (APR: 2.38, CI: 1.43 to 3.97), non-binary individuals (APR: 3.32, CI: 1.35 to 8.18), and LGBA individuals (APR: 1.68, CI: 1.02 to 2.75). Although men reported higher SV and rape levels than women in descriptive and bivariate analyses, these differences were not significant in multivariate analyses. Perpetrators included strangers (46.3%), partners (24.8%), family/friends (15.8%), and colleagues (15.4%). Most survivors did not report SV (63.7%) but confided in friends/relatives (29%) and trusted individuals like teachers/counselors (9.5%), with fewer reporting to authorities (3.4%).

Conclusion

The findings urge policymakers to prioritize targeted interventions, raise awareness, provide comprehensive support services tailored to the diverse needs of migrant groups, various perpetrator types, and the individual, systemic, and structural factors influencing reporting behaviors. These initiatives should adopt a migration-trajectory approach that recognize that migrants may have experienced SV throughout their journey and consider the unique experiences and vulnerabilities of non-binary individuals, LGBA individuals, those with low education levels, and migrants without formal residence status, regardless of their origin.