bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of Wharton’s jelly MSCs secretomes for restoring busulfan-induced reproductive toxicity in male mice
Authors: Bahmyari Sedigheh , Alaee Sanaz , Khodabandeh Zahra , Talaei-Khozani Tahereh , Dara Mahintaj , Mehdinejadiani Shayesteh , Solati Arezoo
Published: July 2024

Several studies investigated the application of Mesenchymal stem cells (MSCs) for treating spermatogenic disorders. Considering the limitation of MSC application, the present study aimed to compare Wharton’s jelly MSCs secretomes, including condition medium (CM) 10-fold concentrated (CM10), 20-fold concentrated CM (CM20), and extracellular vesicles (EVs) to restore busulfan-induced damage on male mice reproduction. So, Wharton’s jelly MSCs were cultured, CM was collected, and EVs were isolated. Seventy-two mice were randomly assigned to nine groups, including Control, Busulfan 1 month (1M), Busulfan 2 months (2M), CM10, Busulfan + CM10, CM20, Busulfan + CM20, EVs, and Busulfan + EVs groups. Sperm characteristics, DNA maturity, DNA fragmentation index (DFI), and testicular gene expression were evaluated. Data analysis revealed that CM10 significantly improved sperm plasma membrane integrity, sperm DNA maturity, and DFI in the Busulfan + CM10 group compared to the Busulfan 2M group. Although CM20 and EVs showed a non-significant improvement. Gene expression analysis showed busulfan administration significantly decreased the expression of AR, CREB1, and PLCζ genes, while CM10 significantly restored CREB1 gene expression. The present study demonstrated that CM10 is more effective than CM20 or EVs in reducing busulfan-induced reproductive toxicity.
A hidden convexity in continuum mechanics, with application to classical, continuous-time, rate-(in)dependent plasticity
Authors: Acharya Amit
Published: July 2024

A methodology for defining variational principles for a class of PDE (partial differential equations) models from continuum mechanics is demonstrated, and some of its features are explored. The scheme is applied to quasi-static and dynamic models of rate-independent and rate-dependent, single-crystal plasticity at finite deformation.
PTBP1 is a potential indicator of disease progression in acute myeloid leukemia
Authors: Xing Lina , Guo Xuefei , Zhang Xiaolei , Wang Ying , He Feng , Ren Jinhai
Published: July 2024

This study aimed to verify a novel potential indicator of disease progression in acute myeloid leukemia (AML) patients. Bone marrow samples were collected from 27 AML patients and 27 controls without hematological malignancies. Polypyrimidine tract-binding protein 1 (PTBP1) expression in bone marrow samples was measured, and the association of PTBP1 with the French–American–British (FAB) classification, cytogenetics, risk stratification, and complete remission (CR) rate was analyzed. The correlation between PTBP1 and Ki-67/p53 expression in AML patients was ultimately evaluated. The results showed that PTBP1 mRNA and protein levels were greater in AML patients than in controls. PTBP1 expression was able to distinguish between AML patients and controls (area under the curve, 0.8601; 95% confidence interval, 0.7632–0.9570). Furthermore, PTBP1 expression was associated with an increased frequency of internal tandem duplication mutations within FMS-like tyrosine kinase-3 (FLT3) and a complex karyotype, while PTBP1 expression was not correlated with FAB classification, monosomal karyotype, isolated biallelic CCAAT/enhancer-binding protein α (CEBPA) mutation, or nucleophosmin 1 (NPM1) mutation in patients with AML. Moreover, PTBP1 expression was associated with a poorer prognosis according to risk stratification and a lower CR rate in AML patients. In addition, PTBP1 expression was positively correlated with the expression of the proliferation marker Ki-67 and negatively correlated with the expression of the apoptosis marker p53 in AML patients. Overall, PTBP1 is a viable biomarker that contributes to the risk prediction and the determination of potential drug targets for AML.
Primary Care Providers’ Experiences With an Active Elective Genetic Testing Program
Authors: Platt Dylan M. , Blout Zawatsky Carrie L. , Christensen Kurt D. , Green Robert C. , Hajek Catherine , Hickingbotham Madison R. , Hutchinson Allison M. , LeBlanc Jessica L. , Zoltick Emilie S. , Jamal Leila
Published: July 2024

Elective genetic testing (EGT) programs that provide pharmacogenomic information to guide medication management and screen for medically actionable disease predispositions are emerging in a number of health systems. Primary care providers (PCPs) are at the forefront of test initiation, patient education, and management of EGT results. However, little research has examined the experiences of PCPs in health systems offering clinical EGT. We conducted semi-structured interviews, a sub-study of the larger mixed-methods Imagenetics Initiative, with 16 PCPs at a health system in the Midwest with a clinical EGT program supported by provider education, automated clinical decision support, and enhanced access to genetic specialists. The purpose of these interviews was to understand perceptions about the benefits and barriers of implementing EGT in clinical practice. Thematic analysis indicated that EGT is conceptualized similar to traditional diagnostic services. PCPs were generally favorable toward EGT; however, targeted education did not dispel misconceptions about the goals, results, and limitations of EGT. Most PCPs endorsed the potential utility of EGT. Pharmacogenomic profiling was seen as having more immediate impact for patients than screening for monogenic disease risks. PCPs reported that they weighed discussions about EGT against time limitations and the need to prioritize patients’ existing health concerns. Regardless of their education levels and familiarity with genetics, PCPs desired additional educational resources and greater access to genetic specialists. Our study provides unique insight into PCPs’ experiences with clinical EGT in health systems that have adopted EGT and highlights the practical challenges and potential opportunities of EGT integration.
The first global landscape analysis of multiple sclerosis research funding
Authors: Bebo Bruce , Coetzee Tim , Gray Emma , Helme Anne , Kanellis Pamela , Landsman Douglas , Mai Michaela , Martinez de la Cruz Beatriz , Morahan Julia , Plassart Emmanuelle , Pickrell Baylee , Rawlings Sarah , Skovgaard Lasse , Zaratin Paola , Rechtman Lindsay
Published: July 2024

Introduction:

Multiple sclerosis (MS) is an immune-mediated central nervous system disorder and a growing global health challenge affecting nearly 3 million people worldwide. Incidence and prevalence continue to increase with no known cause or cure. Globally governments and non-profit organizations fund research toward better understanding of and treatments for multiple sclerosis.

Methods:

This study identified MS research projects funded between 2021 and 2023 by government and non-profit organization sources. Projects were described by type of scientific approach, Pathways to Cure research category (i.e. Stop, Restore, End), and other key characteristics.

Results:

Over 2,300 MS research projects were identified through 16 non-profit MS organizations and 18 government databases. The overall global portfolio of these projects is valued at nearly one and a half billion Euros. The majority of projects were classified in the Stop category (60%). Research collaboration occurs in many forms among the research community; around 272 projects were reported to be co-funded.

Conclusion:

Global MS research collaboration will accelerate progress toward increased knowledge, effective treatments, improved health outcomes, and ultimately cures for MS. This landscape analysis highlights the current distribution of MS research investment between topics and begins to suggest where the MS community should focus to increase potential impact for current and future endeavors.
Emotion dysregulation in autism: A meta-analysis
Authors: McDonald Rachel G. , Cargill Mary Isaac , Khawar Sadaf , Kang Erin
Published: July 2024

Autism is associated with significantly higher rates of internalizing and externalizing disorders compared to neurotypical (NT) individuals. Emotion dysregulation (ED) is prevalent in autistic individuals and has been proposed to underlie both internalizing disorders and behavioral challenges in autism. This study sought to use a meta-analytic approach to examine the magnitude of ED severity in autistic samples compared to NT and other clinical (OC) samples. Following a review of the literature, a total of 35 studies were included in the analyses. In general, when comparing autistic to non-autistic individuals, findings suggest a medium magnitude of difference in ED severity between autistic and comparison groups overall. Subgroup analyses indicate that autistic individuals experience significantly higher ED severity when compared to NT peers. However, when compared to OC peers, the effect is small, suggesting the severity of ED may be more similar between OC and autistic groups. Moderators were also explored, including autistic traits, age, and sex composition. These findings provide integral information about the severity of ED in autistic populations compared to other non-autistic populations, assisting in further clarifying the presence of mental health challenges in autistic youth.

Lay Abstract

Autistic people often experience other mental health challenges, which makes it particularly important to understand factors that may contribute to the development of these conditions. Emotion dysregulation, or difficulties in effectively regulating one’s own emotions in response to a changing environment, is one factor that is experienced frequently by autistic and non-autistic people and is commonly related to a wide range of mental health conditions. This article represents a quantitative synthesis of the current state of the literature on emotion dysregulation, with a specific focus on how the severity of emotion dysregulation differs across autistic and non-autistic people across the lifespan. The findings suggest elevated emotion dysregulation in autistic individuals compared to both neurotypical and other clinical populations and provide insights into the experiences of emotion dysregulation in autistic people. Overall, this article underscores the importance of more research into emotion dysregulation in autistic people to inform areas of challenges related to emotion dysregulation that can be used to better inform treatment targets.
Switching within versus out of class following first-line TNFi failure in ulcerative colitis: real-world outcomes from a German claims data analysis
Authors: Zhuleku Evi , Wirth Daniel , Nissinen Riikka , Bravatà Ivana , Ziavra Despina , Duva Andreas , Lee Jennifer , Fuchs Andreas , Mueller Sabrina , Wilke Thomas , Bokemeyer Bernd
Published: July 2024

Background:

Biologic agents have demonstrated efficacy in treating ulcerative colitis (UC); however, treatment failure to tumor necrosis factor inhibitors (TNFi) is common in the real world. Data on preferential sequencing in clinical practice after failure remain limited.

Objectives:

This study aimed to evaluate real-world outcomes of patients cycling to TNFis or switching to non-TNFi biologics following first-line failure with TNFis.

Design:

Retrospective cohort study in Germany.

Methods:

Adult patients with UC were identified using administrative claims data from 1 May 2014 to 30 June 2022 provided by a statutory sickness fund. Patients newly initiating first-line therapy with TNFis and then switching to another agent were identified. Patients were defined as within-class switched (WCS), if they cycled to another TNFi, or outside-class switchers (OCS), if they switched to a non-TNFi biologic [ustekinumab (UST) or vedolizumab (VDZ)] and followed from index (switch date) to death, insurance end, or study end on 30 June 2022. Inverse probability of treatment weighting (IPTW) was performed to adjust for differences in baseline characteristics between groups, and weighted Cox regression models were used to compare primary (time to discontinuation and second treatment switch) and secondary outcomes (corticosteroid-free drug survival).

Results:

We identified 166 patients initiating TNFis and switching to a subsequent treatment (mean age: 42.9 years, 49.4% female). Following IPTW, there were 71 and 76 patients in the WCS and OCS groups, respectively. Compared to OCS, WCS were more likely to discontinue the new therapy [hazard ratio (HR), 1.82, 95% confidence interval (CI), 1.14–2.89, p = 0.012], and switch a second time (HR, 3.46, 95% CI, 1.89–6.36, p < 0.001). Moreover, WCS showed an increased likelihood of initiating prolonged corticosteroid therapy (HR, 1.42, 95% CI, 0.77–2.59, p = 0.260); however, the results were not significant.

Conclusion:

Following first-line TNFi failure, this study suggests that real-world outcomes among patients with UC are less favorable when cycling to another TNFi, compared to switching to a non-TNFi such as UST or VDZ.
Network meta-analysis of novel targeted therapies for relapsed/refractory chronic lymphocytic leukemia
Authors: Monica Magdalena , Reczek Monika , Kawalec Paweł
Published: July 2024

Background:

The recent development of new antileukemic therapies (anti-CD20 monoclonal antibodies, Bruton tyrosine kinase inhbitors, phosphoinositide 3-kinase inhibitors, and B-cell lymyphoma-2 antagonists) improved the progression-free survival (PFS) compared with selected standard regimens in clinical trials for patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Unfortunately, the relative efficacy of all possible therapeutic options remains unknown because there is no direct evidence for all possible comparisons.

Objectives:

We aimed to compare the efficacy and safety of novel agents, chemotherapy, and immunotherapy using a Bayesian network meta-analysis (NMA).

Design:

Systematic literature review with Bayesian NMA.

Methods:

An extensive systematic literature review of randomized clinical trials for relapsed/refractory CLL was performed. We searched for articles indexed in medical databases (MEDLINE, Embase, The Cochrane Library) and gray literature that could be further implemented into the Bayesian NMA.

Results:

The systematic search identified 15 randomized trials that formed networks comparing PFS, overall survival (OS), overall response rates, and serious adverse events. Our study showed that all regimens containing novel agents significantly prolonged PFS compared with standard chemoimmunotherapy and immunotherapy. Among targeted drugs, venetoclax (VEN) + rituximab (RTX) had comparable efficacy in terms of PFS to zanubrutinib (ZAN) [hazard ratio (95% credible interval), 1.10 (0.59–2.08)], acalabrutinib (ACA) [0.78 (0.47–1.30)], ibrutinib (IBR) monotherapy [0.72 (0.41–1.27)], and other IBR-based regimens. ZAN was superior to IBR monotherapy [0.65 (0.49–0.86)] but not to ACA [0.71 (0.49–1.02)]. There were no significant differences in OS in any of the above comparisons.

Conclusion:

All novel therapies have better efficacy than chemoimmunotherapy and immunotherapy regimens. Among novel agents, the relative efficacy of VEN + RTX was similar to all BTKi, while ZAN was superior to IBR and comparable to ACA.

Trial registration:

PROSPERO CRD42022304330.
Breach diameter prediction of reinforced concrete wall under contact/near-contact explosives using deep neural network
Authors: Holgado David , Montalva Arturo , Florek Jason , Mourão Rodrigo
Published: July 2024

In recent years, the use of Machine Learning (ML) has been expanded to several engineering fields with applications in structural engineering. Deep Neural Network (DNN) models have been widely implemented to predict the response of structural systems under conventional loading. The accuracy of these DNN models relies on the size of the dataset used, which can vary from hundreds to thousands of data points, typically formed by images, test data, and/or finite element models built for a specific environment. Such dependency becomes a limitation when DNN models are intended to be used in blast analysis and/or design, as data are typically scarce or restricted. This paper introduces the implementation of an ML/DNN model for the prediction of breach diameter of a reinforced concrete target subjected to contact and near-contact explosions. The DNN model predicts the breach diameter using experimentally collected concrete breach data. The DNN model considers several parameters related to the charge (e.g., type, geometry, orientation, casement properties) and wall target (e.g., material properties, geometry, reinforcement, fiber content), as well as proximity between the target and explosive. It was found that charge geometry, charge placement type, target thickness, scaled distance, and fiber content in the mix were important features affecting the breach diameter prediction.
Digital Transformation and Breakthrough Innovation in Chinese Manufacturing Firms: Based on Ability-Motivation-Opportunity (AMO) Framework of Human Capital
Authors: Xu Long , Zhou Yunsheng , Chen Liang
Published: July 2024

This paper explores how digital transformation influences breakthrough innovation by adopting the AMO framework of human capital. Through the analysis of data from A-share listed companies in China’s manufacturing industry spanning from 2012 to 2021 using fixed-effect OLS and Sobel test, the study reveals that digital transformation significantly fosters breakthrough innovation within manufacturing companies. This positive impact is attributed to the enhancement of abilities, activation of motivation, and expansion of opportunities for human capital, thus facilitating breakthrough innovation. Furthermore, the study highlights that the impact of digital transformation on breakthrough innovation is particularly pronounced in state-owned and high-tech companies. Additionally, it is observed that companies located in the eastern region of China experiences more robust promotion effects compared to those in central and western regions. Significances and implications are discussed.
Engaging Guest Speakers and Recognizing Their Valuable Contributions to Public Health Classrooms: Process Evaluation of a Pilot Program to Provide Thank You Gift Cards to Guest Speakers
Authors: Walker Elizabeth Reisinger , McGee Robin E.
Published: July 2024

Guest speakers introduce students to diverse perspectives, share relevant experiences that reinforce course content, and demonstrate how skills and knowledge that students are learning can be applied in public health practice. Providing a monetary thank you gift is one way to recognize the valuable contributions of community-based guest speakers to students’ learning. We describe the implementation and evaluation of a departmental pilot program to offer gift cards to guest speakers. During the 2022 to 2023 academic year, instructors could request a $100 gift card for one guest speaker outside of the university community per course per semester. We evaluated the program to assess the process for distributing gift cards, instructors’ reasons for inviting guest speakers, and students’ perceptions of guest speakers’ contributions to their learning. Data were collected through tracking spreadsheets, an online survey to instructors, and anonymous student course evaluations. Thirty gift cards ($2525 covered by the department) were distributed. Evaluation findings indicate that the program is a feasible way to engage diverse perspectives in the classroom and share applied examples and professional development with students. Specific recommendations that we implemented in the continuation of this program include allowing flexibility in the number and denomination of gift cards, streamlining the process for requesting and distributing gift cards, and providing communications to facilitate consistent and clear information sharing. The Guest Speaker Thank You Gift Program complements and extends the diversity, equity, and inclusion work of the department by supporting the expansion of perspectives shared in classroom and directly acknowledging guest speakers’ contributions.
Empagliflozin’s role in early tubular protection for type 2 diabetes patients
Authors: Zhang Chuangbiao , Ren Weiwei , Lu Xiaohua , Feng Lie , Li Jiaying , Zhu Beibei
Published: July 2024

Background

Patients with type 2 diabetes often face early tubular injury, necessitating effective treatment strategies. This study aimed to evaluate the impact of the SGLT2 inhibitor empagliflozin on early tubular injury biomarkers in type 2 diabetes patients with normoalbuminuria.

Methods

A randomized controlled clinical study comprising 54 patients selected based on specific criteria was conducted. Patients were divided into an intervention group (empagliflozin, n = 27) and a control group (n = 27) and treated for 6 weeks. Tubular injury biomarkers KIM-1 and NGAL were assessed pre- and post-treatment.

Results

Both groups demonstrated comparable baseline characteristics. Post-treatment, fasting and postprandial blood glucose levels decreased similarly in both groups. The intervention group exhibited better improvements in total cholesterol, low-density lipoprotein, and blood uric acid levels. Renal function indicators, including UACR and eGFR, showed greater enhancements in the intervention group. Significant reductions in KIM-1 and NGAL were observed in the intervention group.

Conclusion

Treatment with empagliflozin in type 2 diabetes patients with normoalbuminuria led to a notable decrease in tubular injury biomarkers KIM-1 and NGAL. These findings highlight the potential of SGLT2 inhibitors in early tubular protection, offering a new therapeutic approach.
DGCPPISP: a PPI site prediction model based on dynamic graph convolutional network and two-stage transfer learning
Authors: Feng Zijian , Huang Weihong , Li Haohao , Zhu Hancan , Kang Yanlei , Li Zhong
Published: July 2024

Background

Proteins play a pivotal role in the diverse array of biological processes, making the precise prediction of protein–protein interaction (PPI) sites critical to numerous disciplines including biology, medicine and pharmacy. While deep learning methods have progressively been implemented for the prediction of PPI sites within proteins, the task of enhancing their predictive performance remains an arduous challenge.

Results

In this paper, we propose a novel PPI site prediction model (DGCPPISP) based on a dynamic graph convolutional neural network and a two-stage transfer learning strategy. Initially, we implement the transfer learning from dual perspectives, namely feature input and model training that serve to supply efficacious prior knowledge for our model. Subsequently, we construct a network designed for the second stage of training, which is built on the foundation of dynamic graph convolution.

Conclusions

To evaluate its effectiveness, the performance of the DGCPPISP model is scrutinized using two benchmark datasets. The ensuing results demonstrate that DGCPPISP outshines competing methods in terms of performance. Specifically, DGCPPISP surpasses the second-best method, EGRET, by margins of 5.9%, 10.1%, and 13.3% for F1-measure, AUPRC, and MCC metrics respectively on Dset_186_72_PDB164. Similarly, on Dset_331, it eclipses the performance of the runner-up method, HN-PPISP, by 14.5%, 19.8%, and 29.9% respectively.
AMF inhibit the production of phenolic acid autotoxins at the seed-filling stage in soybeans with continuous monocropping
Authors: Shi Hao , Lu Chengcheng , Wu Yunshu , Wang Lei , Cai Baiyan
Published: July 2024

Background

Soybean is the main oil crop in Northeast China. Continuous monocropping is more commonly used for soybean production due to rising market demand and arable land constraints. However, autotoxic substances, such as phenolic acids, produced by continuously cropped soybean can reduce yield and quality. The mycorrhiza formed of Arbuscular mycorrhizal fungi (AMF) and plant roots regulate the metabolic activities of the host plant and increase its disease resistance. The main purpose of this study was to inhibit the production of phenolic acids and determine the adverse effects on the growth of continuous monocropping soybean by inoculating Funneliformis mosseae (F. mosseae).

Results

Transcriptomics results showed that the production of phenolic acids in continuous monocropping soybean roots was mainly regulated by the expression of the CHS6, PCL1, SAMT, SRG1, and ACO1 genes, and the expression of these genes was significantly downregulated after inoculation with F. mosseae. Metabolomics results showed that continuous monocropping soybean roots inoculated with F. mosseae inhibited phenolic acid production through the phenylpropane biosynthetic, α-linoleic acid, linoleic acid, and other metabolic pathways. Phenolic acids in the phenylpropane metabolic pathway, such as 4-hydroxybenzoic acid, phthalic acid, and vanillic acid, decreased significantly after inoculation with F. mosseae. The combined analysis of the two showed that genes such as YLS9 and ARF3 were positively correlated with 4-hydroxybenzoic acid and so on, while genes such as CHS6 and SRG1 were negatively correlated with butyric acid and so on.

Conclusion

F. mosseae regulated the expression of functional genes and related phenolic acid metabolic pathways produced by continuous monocropping soybean roots, inhibiting the production of phenolic acid autotoxic substances in continuous cropped soybean, and slowing down the disturbance of continuous monocropping. This study provides a new solution for continuous monocropping of plants to overcome the autotoxicity barrier and provides a new basis for the development and utilization of AMF as a biological agent.
Branched-chain amino acids and the risk of hypertension; a persian cohort-based study
Authors: Salimi Zahra , Aminnezhad Kavkani Bahareh , Allahyari Pooneh , Askarpour Seyed Ali , Mahmoudi Zahra , Torkaman Mahdie , Hoseini Mohadeseh Sadat Mousavi , Mousavi Zahra , Tajadod Shirin , Valisoltani Neda , Khoshdooz Sara , Doaei Saeid , Kooshki Akram , Gholamalizadeh Maryam
Published: July 2024

Background

The association of hypertension (HTN) and different types of dietary amino acids is not yet clear. The aim of the present study was to investigate the association of branch chain amino acids (BCAAs) and the prevention of HTN.

Methods

This cross-sectional study was conducted on 4184 people aged 35 to 70 using data from the Sabzevar Persian cohort study in Sabzevar, Iran. Data on dietary intake of BCAAs including leucine, isoleucine, and valine were obtained using a validated Food Frequency Questionnaire (FFQ). Multivariable logistic regression analysis assessed the link between HTN and BCAAs.

Results

The results showed that participants with HTN had a higher total protein and BCAAs intake than participants with normal BP (P < 0.01). A marginally significant association was found between the risk of HTN with the total intake of BCAAs (OR = 1.018, CI95%: 1.001–1.035, P = 0.04), leucine (OR = 1.040, CI95%:1.002–1.080, P = 0.03), isoleucine (OR = 1.068, CI95%:1.001–1.140, P = 0.04), and valine (OR = 1.060, CI95%:1.003–1.121, P = 0.04). However, the association disappeared after adjusting the total protein and calorie intake.

Conclusions

The results indicated that the dietary intake of BCAAs may be associated with the risk of HTN. Future longitudinal research is warranted.
Characteristics of blunt and penetrating trauma among victims of physical violence: A retrospective study
Authors: Zohrevandi Behzad , Shahrestani Mahsa Farzaneh , Mohammadnia Hamideh , asadi Kamran , Khodadadi-Hassankiadeh Naema
Published: July 2024

Background

A significant number of referrals to the emergency departments is due to violence and conflict leading to serious injuries and death. The increasing number of such cases highlights the urgent need for investigating victimization of physical violence.

Aim

The purpose of this study was to determine the frequency of demographic and clinical characteristics in victims of violence and classify them based on penetrating or blunt trauma.

Methods

The data of the patients who had been the victims of violence in 2020 were extracted from the Trauma Registry System(TRS) of the Guilan Road Trauma Research Center(GTRC). All analyses were performed using SPSS software version 24. The significance level was considered less than 0.05.

Results

There was a significant difference in the type of violence-related trauma in different age groups (P < 0.001), based on sex (P = 0.002), and marital status (P = 0.012). A significant difference also existed between the trauma type and clinical variables including smoking (P = 0.032), history of alcohol drinking (P = 0.005), and other substance use (P = 0.002), the anatomical location of injury (P < 0.001) and therapeutic interventions (p < 0.001(.

Conclusion

Most of the clients of the violence suffered from blunt trauma, the severity of which was mild, and they were treated supportively without the need for surgery. Blunt trauma was seen more in women, divorcees, over 40 years and non-smokers. Penetrating trauma was observed more in lower limb injuries and alcohol and amphetamine users. Prevention programs and educational interventions should be programmed for the society long before men alcohol and amphetamine abusers reach their fourth decade of life. Accurately recording the type of physical violence, and the weapon used, and determining the injury severity score in TRS can lead to more reliable results in researching the field of violence issues.
Social support resources in adolescents and young adults with advanced cancer: a qualitative analysis
Authors: Lau Nancy , Steineck Angela , Walsh Casey , Fladeboe Kaitlyn M. , Yi-Frazier Joyce P. , Rosenberg Abby R. , Barton Krysta
Published: July 2024

Purpose

Adolescents and Young Adults (AYAs) with cancer are an at-risk group with unique palliative and supportive care needs. Social support in AYAs with cancer is associated with better coping, quality of life, and psychosocial well-being. Here, we extend existing research to examine the sources and types of support received by AYAs with advanced cancer.

Methods

AYAs participated in a semi-structured, 1:1 interview on communication and psychosocial support needs. The present analysis focused on social support experiences for AYAs with advanced cancer. Directed content analysis was used to develop the codebook. Established social support constructs provided a coding framework. We presented our qualitative findings as a code frequency report with quantified frequency counts of all “source of support” and “type of support” codes. We assigned a global “sufficiency of support code” to each AYA.

Results

We interviewed 32 AYAs with advanced cancer (Mage = 18, SDage = 3.2, 41% female). Most AYAs identified family (namely, caregivers) as their primary source of support and stated that family universally provided all types of support: emotional, informational, instrumental, and social companionship. They received informational and emotional support from clinicians, and received emotional support and social companionship from healthy peers, cancer peers, and their existing community. One-third of participants were coded as having “mixed support” and described a lack of support in some domains.

Conclusion

AYAs with advanced cancer described caregivers as their universal source of support, and that other support sources provided support for specific needs. Future research should continue to evaluate social support needs and family-based palliative and supportive care interventions to bolster social support resources in this high-risk group.
CRISPR-Cas9 knockout screen informs efficient reduction of the Komagataella phaffii secretome
Authors: Dalvie Neil C. , Lorgeree Timothy R. , Yang Yuchen , Rodriguez-Aponte Sergio A. , Whittaker Charles A. , Hinckley Joshua A. , Clark John J. , Del Rosario Amanda M. , Love Kerry R. , Love J. Christopher
Published: July 2024

Background

The yeast Komagataella phaffii is widely used for manufacturing recombinant proteins, but secreted titers of recombinant proteins could be improved by genetic engineering. In this study, we hypothesized that cellular resources could be redirected from production of endogenous proteins to production of recombinant proteins by deleting unneeded endogenous proteins. In non-model microorganisms such as K. phaffii, however, genetic engineering is limited by lack gene annotation and knowledge of gene essentiality.

Results

We identified a set of endogenous secreted proteins in K. phaffii by mass spectrometry and signal peptide prediction. Our efforts to disrupt these genes were hindered by limited annotation of essential genes. To predict essential genes, therefore, we designed, transformed, and sequenced a pooled library of guide RNAs for CRISPR-Cas9-mediated knockout of all endogenous secreted proteins. We then used predicted gene essentiality to guide iterative disruptions of up to 11 non-essential genes. Engineered strains exhibited a ~20× increase in the production of human serum albumin and a twofold increase in the production of a monoclonal antibody.

Conclusions

We demonstrated that disruption of as few as six genes can increase production of recombinant proteins. Further reduction of the endogenous proteome of K. phaffii may further improve strain performance. The pooled library of secretome-targeted guides for CRISPR-Cas9 and knowledge of gene essentiality reported here will facilitate future efforts to engineer K. phaffii for production of other recombinant proteins and enzymes.
Associations between dietary total antioxidant capacity and sarcopenia: a cross-sectional study
Authors: Aminianfar Azadeh , Hashemi Rezvan , Emami Fatemeh , Heshmat Ramin , Motlagh Ahmadreza Dorosty , Esmaillzadeh Ahmad
Published: July 2024

Background

No study has investigated the relationship between dietary total antioxidant capacity and sarcopenia so far.

Objective

This study aimed to investigate the association between dietary Total Antioxidant Capacity (d-TAC) and sarcopenia in elderly adults.

Methods

In this cross-sectional study we enrolled 300 elderly people (150 men and 150 women) aged ≥ 55 years using cluster random sampling method. Sarcopenia was defined based on European Working Group on Sarcopenia (EWGSOP) definition. A DXA scanner, a squeeze bulb dynamometer and a 4-Meter walk gait speed test was used to measure Appendicular Skeletal Muscle (ASM), muscle strength and muscle performance respectively. We also used a Block-format 117-item food frequency questionnaire (FFQ) to assess dietary intakes of participants. Multivariable logistic regression models were applied to examine the association between d-TAC and sarcopenia.

Results

Mean ± SD age of study participants and their BMI was 66.8 ± 7.72 year and 27.3 ± 4.2 kg/m2, respectively. People in the highest tertile of d-TAC had the greatest hand grip strength (11.9 ± 3.63 vs. 10.4 ± 3.55 psi, p = 0.009) and had lower odds of sarcopenia compared with those in the lowest tertile, either before (OR = 0.39; 95% CI: 0.17, 0.88) or after adjustment for potential confounders (OR = 0.33; 95% CI: 0.11, 0.95). No other significant association was seen between d-TAC and components of sarcopenia.

Conclusion

We found an inverse association between dietary total antioxidant capacity and odds of sarcopenia. No significant association was seen between d-TAC and individual components of sarcopenia. Further studies are needed to confirm our findings.
Different trends in suicide rates among foreign residents in Japan and Japanese citizens during the COVID-19 pandemic
Authors: Taniguchi Yuta , Tamiya Nanako , Iwagami Masao , Yamagishi Kazumasa , Miyawaki Atsushi , Masuda Rie , Kihara Tomomi , Komiyama Jun , Tachikawa Hirokazu , Takahashi Hideto , Iso Hiroyasu
Published: July 2024

Background

Suicide rates in Japan have increased during the COVID-19 pandemic, and foreign residents may be more vulnerable to mental stress during such crises. Therefore, we aimed to compare the trends in suicide rates during the COVID-19 pandemic between foreign residents and Japanese citizens.

Methods

Vital statistics of Japan data from January 1, 2016 to December 31, 2021 were used to calculate quarterly sex-specific suicide rates for foreign residents and Japanese citizens. An event-study analysis was conducted to evaluate whether suicide rates during the COVID-19 pandemic increased compared to pre-pandemic estimates; foreign residents and Japanese citizens were compared using difference-in-difference-in-differences estimates.

Results

Between 2016 and 2021, 1,431 foreign residents and 121,610 Japanese citizens died from suicide in Japan. Although the suicide rate for foreign residents was lower than that for Japanese citizens, Korean residents, who comprise approximately half of the foreign decedents, had largely higher suicide rates than Japanese citizens. The event-study analysis indicated that suicide rates increased among foreign residents for both men and women, and continued for men by the end of 2021. In Japanese citizens, after a decline in suicide rates in the second quarter of 2020, suicide rates increased both among men and women, and lasted for women until the fourth quarter of 2021. The difference-in-difference-in-differences analyses confirmed the initial decline in the second quarter of 2020 in suicide rate only in Japanese men and women, and the persistent increase through 2021 in foreign men.

Conclusions

We found differential trends in suicide rates between foreign and Japanese men and women during the COVID-19 pandemic featuring a persistent increase in foreign men. Suicide prevention measures should be focused on these high-risk subpopulations.
PARP-1, EpCAM, and FRα as potential targets for intraoperative detection and delineation of endometriosis: a quantitative tissue expression analysis
Authors: Belmonte Beatrice , Di Lorenzo Giovanni , Mangogna Alessandro , Bortot Barbara , Bertolazzi Giorgio , Sammataro Selene , Merighi Simona , Martorana Anna , Zito Gabriella , Romano Federico , Giorgiutti Anna , Bottin Cristina , Zanconati Fabrizio , Romano Andrea , Ricci Giuseppe , Biffi Stefania
Published: July 2024

Background

Endometriosis is a gynecological disease characterized by the presence of endometrial tissue in abnormal locations, leading to severe symptoms, inflammation, pain, organ dysfunction, and infertility. Surgical removal of endometriosis lesions is crucial for improving pain and fertility outcomes, with the goal of complete lesion removal. This study aimed to analyze the location and expression patterns of poly (ADP-ribose) polymerase 1 (PARP-1), epithelial cell adhesion molecule (EpCAM), and folate receptor alpha (FRα) in endometriosis lesions and evaluate their potential for targeted imaging.

Methods

Gene expression analysis was performed using the Turku endometriosis database (EndometDB). By immunohistochemistry, we investigated the presence and distribution of PARP-1, EpCAM, and FRα in endometriosis foci and adjacent tissue. We also applied an ad hoc platform for the analysis of images to perform a quantitative immunolocalization analysis. Double immunofluorescence analysis was carried out for PARP-1 and EpCAM, as well as for PARP-1 and FRα, to explore the expression of these combined markers within endometriosis foci and their potential simultaneous utilization in surgical treatment.

Results

Gene expression analysis revealed that PARP-1, EpCAM, and FOLR1 (FRα gene) are more highly expressed in endometriotic lesions than in the peritoneum, which served as the control tissue. The results of the immunohistochemical study revealed a significant increase in the expression levels of all three biomarkers inside the endometriosis foci compared to the adjacent tissues. Additionally, the double immunofluorescence analysis consistently demonstrated the presence of PARP-1 in the nucleus and the expression of EpCAM and FRα in the cell membrane and cytoplasm.

Conclusion

Overall, these three markers demonstrate significant potential for effective imaging of endometriosis. In particular, the results emphasize the importance of PARP-1 expression as a possible indicator for distinguishing endometriotic lesions from adjacent tissue. PARP-1, as a potential biomarker for endometriosis, offers promising avenues for further investigation in terms of both pathophysiology and diagnostic-therapeutic approaches.
Carotid body tumor: characteristics and surgical outcome
Authors: Kakamad Fahmi Hussein , Mustafa Mihr Naif , Yasin Shara Wahdaldeen , Xalid Shanga Sherzad , Mohammed Ayoob A. , Othman Snur , Hiwa Dilan S. , Abdullah Hiwa O. , Abdalla Berun A. , Nasralla Hawkar A. , Ahmed Sasan M. , Mustafa Ayman M. , Hassan Shko H. , Hussein Bushra O.
Published: July 2024

Background

Carotid body tumors are uncommon neuroendocrine growths near the carotid bifurcation. While some advocate preoperative embolization to minimize bleeding, others avoid it due to complications. This study shares the experience of a single center in managing patients with carotid body tumors without practicing preoperative embolization.

Methods

This was a cross-sectional study of patients with carotid body tumors managed between 2020 and 2024. Data were collected from the hospital’s registry. When necessary, routine blood tests, neck ultrasonography, and computed tomography scans were conducted. The tumors were categorized according to Shamblin’s classification. The average duration of follow-up was 20 months.

Results

The study involved 25 patients, 22 (88%) females and 3 (12%) males. Their ages ranged from 27 to 85 years old. Twenty (80%) cases presented with neck swelling, and six (24%) had a positive medical history. Tumors were mainly on the right side (52%), with 20 (80%) showing ill-defined neck masses. Tumor sizes ranged from 1.5 to 7 cm, with Shamblin type II tumors being discovered in the majority of cases (72%). Types of tumors were significantly associated with the tumor size (p-value < 0.05). Blood transfusion was required in five cases (20%), three from type III and two from type II, with none from type I (p-value = 0.001). Temporary neurological deficits occurred in 3 cases (12%). No functional impairment or mortality was recorded.

Conclusions

Carotid body tumors are rare tumors with an unknown etiology. Operation without practicing preoperative embolization may be feasible with an acceptable outcome.
In silico insights into the design of novel NR2B-selective NMDA receptor antagonists: QSAR modeling, ADME-toxicity predictions, molecular docking, and molecular dynamics investigations
Authors: El fadili Mohamed , Er-rajy Mohammed , Mujwar Somdutt , Ajala Abduljelil , Bouzammit Rachid , Kara Mohammed , Abuelizz Hatem A. , Er-rahmani Sara , Elhallaoui Menana
Published: July 2024

Based on a structural family of thirty-two NR2B-selective N-Methyl-D-Aspartate receptor (NMDAR) antagonists, two phenylpiperazine derivatives labeled C37 and C39 were conceived thanks to molecular modeling techniques, as novel NMDAR inhibitors exhibiting the highest analgesic activities (of pIC50 order) against neuropathic pain, with excellent ADME-toxicity profiles, and good levels of molecular stability towards the targeted protein of NMDA receptor. Initially, the quantitative structure-activity relationships (QSARs) models were developed using multiple linear regression (MLR), partial least square regression (PLSR), multiple non-linear regression (MNLR), and artificial neural network (ANN) techniques, revealing that analgesic activity was strongly correlated with dipole moment, octanol/water partition coefficient, Oxygen mass percentage, electronegativity, and energy of the lowest unoccupied molecular orbital, whose the correlation coefficients of generated models were: 0.860, 0.758, 0.885 and 0.977, respectively. The predictive capacity of each model was evaluated by an external validation with correlation coefficients of 0.703, 0.851, 0.778, and 0.981 respectively, followed by a cross-validation technique with the leave-one-out procedure (CVLOO) with Q2cv of 0.785, more than Y-randomization test, and applicability domain (AD), in addition to Fisher’s and Student’s statistical tests. Thereafter, ten novel molecules were designed based on MLR QSAR model, then predicted with their ADME-Toxicity profiles and subsequently examined for their similarity to the drug candidates. Finally, two of the most active compounds (C37 and C39) were chosen for molecular docking and molecular dynamics (MD) investigations during 100 ns of MD simulation time in complex with the targeted protein of NMDA receptor (5EWJ.pdb).
Pricing of insurance-linked securities: a multi-peril approach
Authors: Burnecki Krzysztof , Teuerle Marek A. , Zdeb Martyna
Published: July 2024

In this paper we build a methodology for pricing of insurance-linked securities which are tied to multiple natural catastrophe perils. As a representative example, we construct a multi-peril catastrophe (CAT) bond which can be linked to the industry loss indices or actual losses incurred by an insurer. We provide pricing formulas for such CAT bonds. We illustrate the introduced methodology on the US natural catastrophe data obtained from Property Claim Services (PCS). Within this dataset, we specifically examine two types of risks: losses associated with wind and thunderstorm events, and those linked to winter storm events. Then, we fit and validate the underlying compound non-homogeneous Poisson processes taking into account the fact that the data are left-truncated. The best fitted loss distributions appear to be Burr and Generalised Extreme Value and for the first peril and log-normal for the second. Finally, we visualise the zero-coupon CAT bond prices for the selected best-fitted models.
Ultrasound-guided perineural injection of the saphenous nerve in goat cadavers
Authors: Torruella Xavier , Puggioni Antonella , Santos Bruno , Brama Pieter , Huuskonen Vilhelmiina
Published: July 2024

Background

Surgery of the goat stifle joint requires good perioperative analgesia, ideally without affecting motor function in the postoperative period. 

The objective of this study was to describe an ultrasound-guided technique for saphenous nerve block in goats. Eleven fresh female goat cadavers from two different age groups were used: seven of them were four years old with a mean ± SD body weight of 65.9 ± 7.3 kg. Four animals were six months old and their mean ± SD body weight was 20.1 ± 3.1 kg. The cadavers were positioned in lateral recumbency with the limb to be blocked lowermost. A high-frequency linear transducer (6–12 MHz) was used to localise the interfascial plane between the sartorius and the vastus medialis muscles and to identify the saphenous nerve on the medial aspect of the thigh, caudal to the femur, at the level of the femoral triangle. In 22 pelvic limbs 0.1 mL/kg of methylene blue was injected around the saphenous nerve under ultrasound guidance, followed by gross anatomical dissection. The length of circumferentially stained nerve was measured, and the success rate of achieving at least 1 cm of staining is presented with a 95% confidence interval (CI).

Results

Although not all saphenous nerves were sonographically identified, their boundaries were defined as cranial to the femoral artery, lateral to the sartorius muscle, and medial to the vastus medialis and rectus femoris muscles, within the perivascular fat. During anatomical dissection, the overall dye solution distribution was graded as complete in 17/22 limbs indicating a 77.3% success rate [95% CI (0.598, 0.948)], partial in 3/22 limbs and failed in 2/22 limbs.

Conclusions

The success rate of this study indicates the feasibility of employing the ultrasound-guided technique to perform saphenous nerve block in goats. However, further in-vivo studies are recommended to assess the block's clinical efficacy before implementation on clinical patients.