bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of Childbirth Self-Efficacy Enhancing Classes on Labor Length and Outcomes among Egyptian Primiparous Women: A Quasi-Experimental Study
Authors: Abd El-Kader Azza Ibrahim
Published: October 2024

Introduction

Childbirth self-efficacy has repeatedly been shown to raise satisfaction with childbirth, reduce the need for analgesic, and promote the use of different childbirth alternatives. However, the measures to improve the childbirth self-efficacy had rarely been investigated among Egyptian primiparous women.

Aim

The aim of this study is to evaluate the effectiveness of childbirth self-efficacy enhancing classes on labor length and outcomes among Egyptian primiparous women.

Methods

A quasi-experimental research approach was carried out on prospective, consecutive sample of 148 pregnant women at the end of pregnancy. A prenatal education study group (n = 74) and a control group receiving standard antenatal care (n = 74) make up the first and second groups, respectively. Between October 2021 and October 2022, the study was conducted at the antenatal clinic. The following four tools were employed to fulfill the study's objective: A structured interviewing form, a childbirth self-efficacy inventory, a follow-up checklist for monitoring maternal and neonatal outcomes during labor, and three antenatal education sessions to boost childbirth self-efficacy are all examples of tools that can be used. All statistical analyses were performed using SPSS for windows version 20.0

Results

Approximately 68.9% of women in the experimental group gave birth vaginally, compared to 29.7% of those in the control group with (p = .001), according to the study's findings. In the experimental group, regular labor took an average of 8 to 12 h, but it took more than 12 h in the control group. Birth weight (>3000g) in the experimental group compared to (2000–3000 g) in the control group, as well as the Apgar score at 1 min and 5 min, were highly statistically significance between two groups with (p = .001). The means±SD of the childbirth self-efficacy result scores were better in the study group than in control groups regarding length of delivery and vaginal delivery (248.2 ± 19.4 versus 144.6 ± 21.6 and 250.1 ± 18.2 versus 137.9 ± 21.5, respectively).

Conclusion

According to the findings of this study, antenatal education classes have a real chance of assisting primiparous women in increasing their childbirth self-efficacy and improving maternal and neonatal outcomes.
Ultrasound Shear Wave Elastography of the Arch-Supporting Structures in Symptomatic Flatfoot: A Pilot Study
Authors: Latt L. Daniel , Kim Wonsuk , Caruso Chelsea C. , Krupinski Elizabeth A. , Zuniga Andres Angel Nuncio , Syal Amit , Taljanovic Mihra S.
Published: October 2024

Background:

The posterior tibial tendon (PTT), deltoid ligament, and spring ligament are often torn or attenuated in patients with progressive collapsing foot deformity. The goal of this pilot study was to measure the ultrasound shear wave velocity (SWV) of these arch-supporting structures in feet with varying degrees of deformity to improve our understanding of their role in the progression of deformity.

Methods:

Two observers measured the SWV of the supramalleolar and inframalleolar PTT in long and short axes, in the tibiospring portion of the deltoid ligament, and in the superomedial band of the spring ligament in 8 neutrally aligned feet, 5 asymptomatic flatfeet, and 7 symptomatic flatfeet. Each measurement was repeated 3 times both with and without an applied eversion stress.

Results:

Average SWV was lower at all locations in the symptomatic flatfeet compared with normal feet, but these differences were statistically significant only for the inframalleolar PTT and the spring ligament. Externally applied stress led to an increase in the SWV of the ligaments but a paradoxical decrease in the SWV in the supramalleolar PTT. The SWV of the PTT was lower along the short axis compared with the long axis.

Conclusion:

SWV may be useful in evaluating the severity of degenerative disease of arch-supporting structures, but further study is needed before this technique can be applied clinically.

Level of Evidence:

Level III, case-control study.
Analysing Delhi’s Prosperity: A Brief Commentary
Authors: Kanupriya Mrs
Published: October 2024

Delhi is a historical hub for regional, national and international commerce and a place for the socio-political elites. The city is widely considered to be prosperous. This study is an attempt at understanding Delhi’s affluence using both existing literature and data from Aspirational India, Consumer Pyramids Household Survey, 2024, Economic Survey of Delhi, 2023–2024 and Multiple Indicator Survey, 2020–2021. The city of Delhi faces significant challenges in terms of housing quality, access to clean drinking water, electricity connections and asset ownership among different socio-economic groups. It is essential to work towards making these facilities and assets more equitable and accessible to all its residents. Furthermore, enhancing coordination among various levels of government is crucial to ensure a better quality of life for all individuals living in the city. Addressing the pressing issue of limited prosperity in Delhi requires urgent attention and action, given the financial struggles faced by its residents on a daily basis.
Neuroimaging and the Investigation of Drug-Drug Interactions Involving Psychedelics
Authors: Wall Matthew B , Harding Rebecca , Ertl Natalie , Barba Tommaso , Zafar Rayyan , Sweeney Mark , Nutt David J , Rabiner Eugenii A , Erritzoe David
Published: October 2024

Psychedelic therapies are an emerging class of treatments in psychiatry with great potential, however relatively little is known about their interactions with other commonly used psychiatric medications. As psychedelic therapies become more widespread and move closer to the clinic, they likely will need to be integrated into existing treatment models which may include one or more traditional pharmacological therapies, meaning an awareness of potential drug-drug interactions will become vital. This commentary outlines some of the issues surrounding the study of drug-drug interactions of this type, provides a summary of some of the relevant key results to date, and charts a way forward which relies crucially on multimodal neuroimaging investigations. Studies in humans which combine Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI), plus ancillary measures, are likely to provide the most comprehensive assessment of drug-drug interactions involving psychedelics and the relevant effects at multiple levels of the drug response (molecular, functional, and clinical).
AI and Actors: Ethical Challenges, Cultural Narratives and Industry Pathways in Synthetic Media Performance
Authors: Thomas Sarah
Published: October 2024

The article explores the growing use of artificial intelligence (AI) in the entertainment industry, focusing on the impact to screen and audio performers. AI technologies enable the creation of synthetic performances, raising ethical concerns regarding identity manipulation, consent, and performer rights. Ethical AI should prioritize human-centric values such as transparency, accountability, and fairness, but many principles remain abstract and difficult to implement. Examining the intersection of acting and AI – in terms of working practice and discursive narratives used to situate that work – highlights significant issues about responsible AI use, the mechanics of media production, and the management of digitised identities. It stands as a useful model through which to explore and advance concepts of responsible AI practice and rhetoric. The article examines the role of fraudulent and exploitative uses of performer likenesses, how synthetic performance is enhancing celebrity brand identities, and evolving regulatory measures governing performer intellectual property (IP) across the U.S. and UK media industries. Performers are increasingly negotiating licensing and legal agreements to protect their likenesses, but current protections benefit primarily well-known stars over others. The article underscores the need for systemic frameworks to ensure responsible AI use, emphasizing the critical role performers play as both data sources and cultural agents, influencing public trust in AI technologies.
Influence of Multiple Repair Welding on Microstructure and Properties of 06Cr19Ni10 Stainless Steel
Authors: Liu Qimeng , Chang Jingyu , Wang Yuanzhi , Xia Dong , Zhang Jianfei , Guan Xinlong , Zhou Yuwei , Yang Bing
Published: October 2024

Repair welding technology is widely used in the manufacturing and maintenance of rail transit equipment to repair welding defects. However, repair welding induces modifications in joint performance, and it is necessary to study the microstructure evolution behavior to reveal the reasons. In this study, the effects of multiple repair welding on the microstructure, mechanical, and fatigue properties of 06Cr19Ni10 stainless steel samples were studied. The surface texture and fracture morphology analyses of the samples were conducted by optical microscopy (OM), scanning electron microscopy (SEM), and its equipped backscattered electron diffraction (EBSD) technique. The mechanical and fatigue properties of the samples with different repair welding times were further obtained by hardness, tensile, and fatigue tests. The results show an increase in the grain size and the substructure content in the heat-affected zone (HAZ), and the austenite orientation is changed, attributable to multiple repair welding. Multiple heat inputs result in a significant increase in hardness from 165 HV to 185 HV, a noticeable decrease in tensile strength and elongation, and an upward trend in yield strength. Under the constant stress level, the heat input of multiple repair welding causes a decrease in the fatigue life and significantly reduces toughness in the instantaneous fracture zone of the secondary repair sample.
Caspase-8 in inflammatory diseases: a potential therapeutic target
Authors: Zhang Wangzheqi , Zhu Chenglong , Liao Yan , Zhou Miao , Xu Wenyun , Zou Zui
Published: October 2024

Caspase-8, a renowned cysteine-aspartic protease within its enzyme family, initially garnered attention for its regulatory role in extrinsic apoptosis. With advancing research, a growing body of evidence has substantiated its involvement in other cell death processes, such as pyroptosis and necroptosis, as well as its modulatory effects on inflammasomes and proinflammatory cytokines. PANoptosis, an emerging concept of cell death, encompasses pyroptosis, apoptosis, and necroptosis, providing insight into the often overlapping cellular mortality observed during disease progression. The activation or deficiency of caspase-8 enzymatic activity is closely linked to PANoptosis, positioning caspase-8 as a key regulator of cell survival or death across various physiological and pathological processes. Aberrant expression of caspase-8 is closely associated with the development and progression of a range of inflammatory diseases, including immune system disorders, neurodegenerative diseases (NDDs), sepsis, and cancer. This paper delves into the regulatory role and impact of caspase-8 in these conditions, aiming to elucidate potential therapeutic strategies for the future intervention.
Complete genome sequences of two Pantoea stewartii strains ATCC 8199 from maize and PSCN1 from sugarcane
Authors: Chu Na , Liu Tian-Tian , Zhang Hui-Li , Cui Dong , Huang Mei-Ting , Fu Hua-Ying , Su Jun-Bo , Gao San-Ji
Published: October 2024

Objectives

The pathogen of Pantoea stewartii (Ps) is the causal agent of bacterial disease in corn and various graminaceous plants. Ps has two subspecies, Pantoea stewartii subsp. stewartia (Pss) and Pantoea stewartii subsp. indologenes (Psi). This study presents two complete genomes of Ps strains including ATCC 8199 isolated from maize and PSCN1 causing bacterial wilt in sugarcane. The two bacterial genomes information will be helpful for taxonomy analysis in this genus Pantoea at whole-genome levels and accurately discriminated the two subspecies of Pss and Psi.

Data description

The reference strain ATCC 8199 isolated from maize was purchased from Beijing Biobw Biotechnology Co., Ltd. (China) and the strain of PSCN1 was isolated from sugarcane cultivar YZ08-1095 in Zhanjiang, Guangdong province of China. Two complete genomes were sequenced using Illumina Hiseq (second-generation) and Oxford Nanopore (third-generation) platforms. The genome of the strain ATCC 8199 comprised of 4.78 Mb with an average GC content of 54.03%, along with five plasmids, encoding a total of 4,846 gene with an average gene length of 827 bp. The genome of PSCN1 comprised of 5.03 Mb with an average GC content of 53.78%, along with two plasmids, encoding a total of 4,725 gene with an average gene length of 913 bp. The bacterial pan-genome analysis highlighted the strain ATCC 8199 was clustered into a subgroup with a Pss strain CCUG 26,359 from USA, while the strain PSCN1 was clustered into another subgroup with a Ps strain NRRLB-133 from USA. These findings will serve as a useful resource for further analyses of the evolution of Ps strains and corresponding disease epidemiology worldwide.
The validity and reliability of the Arabic version of the EQ-5D in atrial fibrillation patients in a conflict country: a study from Syria
Authors: Antoun Ibrahim , Alkhayer Alkassem , Aljabal Majed , Alkhayer Alamer , Simon Peter , Mahfoud Yaman , Kotb Ahmed , Barker Joseph , Mavilakandy Akash , Somani Riyaz , Ng G Andre , Zakkar Mustafa
Published: October 2024

Background

The EQ-5D is one of the most commonly used tools to establish health-related quality of life (QoL). EQ-5D data in atrial fibrillation (AF) patients in the Middle East are lacking.

Objectives

This study aims to evaluate the reliability and validity of the Arabic version of the EQ-5D in AF inpatients in Syria.

Methods

The study involved patients admitted to the emergency department of Tishreen’s University Hospital in Latakia with AF as the primary diagnosis between the 1st of June 2021 and the 1st of June 2023. Arabic versions of the EQ-5D, EQ-VAS and SF36 questionnaires were administered to patients. Validation was done using convergent, discriminant, and known-groups validity, while reliability was conducted using EQ-5D retesting within 2–4 weeks.

Results

432 participants were included in the study with a mean ± standard deviation of 63 ± 15. Males represented 242 (56%) of the participants. All hypotheses relating EQ-5D responses to external variables were satisfied. All three validation hypotheses demonstrated that the EQ-5D had the convergent, discriminant and known group validity to assess QoL in this cohort. The intraclass correlation coefficient (ICC) for test-retest reliability ranged between 0.74 and 0.88, while Cohen’s κ ranged between 0.72 and 0.86. Cronbach’s α value for internal consistency was 0.73.

Conclusion

The Arabic version of EQ-5D was valid and reliable in measuring QoL in AF inpatients in Syria. This validation opens the door for more widespread use of the EQ-5D in Arabic-speaking regions, facilitating better-informed healthcare decisions and improving patient care strategies in Syria and other Middle Eastern countries.
Pharmacogenomics-assisted treatment versus standard of care in schizophrenia: a systematic review and meta-analysis
Authors: Das Saibal , Kalita Manoj , Makhal Manabendra , Devaraja M , Bagepally Bhavani Shankara , Cherian Jerin Jose , Aadityan Rajesh , Bhattacharjee Mounamukhar , Mondal Sarnendu , Sen Sreyashi , Mondal Manaswini , Basu Aniruddha , Dutta Atanu Kumar , Saha Indranil , Saha Asim , Chakrabarti Amit
Published: October 2024

Background

Pharmacogenomic (PGx) factors significantly influence how patients respond to antipsychotic medications This systematic review was performed to synthesize the clinical utility of PGx-assisted treatment versus standard of care in schizophrenia.

Methods

PubMed, Embase, and Cochrane CENTRAL databases were searched for randomized controlled trials (RCTs) from inception till June 2024 that had compared the clinical utility of PGx-assisted intervention as compared to the standard of care in schizophrenia. The primary outcome was safety, and the secondary outcomes were efficacy and medication adherence. Pooled standardized mean differences (SMD) along with a 95% confidence interval (CI) were calculated (random-effects model) wherever feasible.

Results

A total of 18,821 studies were screened, and five were included for review. All the RCTs had a high risk of bias. Four studies included the commonly used antipsychotics. Three studies reported negative outcomes (safety, efficacy, and medication adherence) and two reported positive outcomes (safety) using different scales. In the meta-analysis, there were significant differences in the total Udvalg for Kliniske Undersogelser Side-Effect Rating scale score [SMD 0.95 (95% CI: 0.76–1.13), p < 0.001); I2 = 0%] and the total Positive and Negative Syndrome Scale score [SMD 10.65 (95% CI: 2.37–18.93), p = 0.01); I2 = 100%] between the PGx-assisted treatment and standard of care arms. However, the results were inconsistent, and the certainty of evidence (GRADE criteria) was very low.

Conclusion

Current evidence on the clinical utility of PGx-assisted treatment in schizophrenia is limited and inconsistent and further evidence is required in this regard.
The dissemination and implementation of trauma-focused cognitive behavioural therapy for children and adolescents in seven European countries
Authors: Pfeiffer Elisa , Unterhitzenberger Johanna , Enderby Pia , Juusola Aino , Kostova Zlatina , Lindauer Ramon J. L. , Nuotio Sanna-Kaija , Samuelberg Poa , Jensen Tine K.
Published: October 2024

Background

There is broad scientific evidence for the effectiveness of individual trauma-focused evidence-based treatments (EBTs) such as “trauma-focused cognitive behavioural therapy” (TF-CBT) for children and adolescents with posttraumatic stress symptoms. However, there is a significant research-to-practice gap resulting in traumatized children in high-income countries in Europe having only very limited access to these treatments. The aim of this study was, therefore, to identify common barriers and successful dissemination and implementation (D&I) strategies of evidence-based trauma-focused treatments (in particular TF-CBT) in seven European countries.

Methods

For this study, we chose a mixed-method approach: an online survey among certified European TF-CBT trainers (N = 22) and the collection of country-based narratives from TF-CBT experts in different European countries (Finland, Germany, Italy, Netherlands, Norway, Sweden).

Results

Common modifiable barriers to the implementation of TF-CBT were identified on different levels (e.g. government or treatment level), and successful D&I strategies were highlighted across all countries, such as translations of materials. Additionally, the experts from the country narratives put together a broad overview of TF-CBT research in Europe.

Conclusions

The results of this study revealed that especially learning collaborations and the development of joint European efforts in funding and researching D&I strategies are crucial for future implementation of trauma-focused EBTs in Europe.
Prediction of homologous recombination deficiency from routine histology with attention-based multiple instance learning in nine different tumor types
Authors: Loeffler Chiara Maria Lavinia , El Nahhas Omar S. M. , Muti Hannah Sophie , Carrero Zunamys I. , Seibel Tobias , van Treeck Marko , Cifci Didem , Gustav Marco , Bretz Kevin , Gaisa Nadine T. , Lehmann Kjong-Van , Leary Alexandra , Selenica Pier , Reis-Filho Jorge S. , Ortiz-Bruechle Nadina , Kather Jakob Nikolas
Published: October 2024

Background

Homologous recombination deficiency (HRD) is recognized as a pan-cancer predictive biomarker that potentially indicates who could benefit from treatment with PARP inhibitors (PARPi). Despite its clinical significance, HRD testing is highly complex. Here, we investigated in a proof-of-concept study whether Deep Learning (DL) can predict HRD status solely based on routine hematoxylin & eosin (H&E) histology images across nine different cancer types.

Methods

We developed a deep learning pipeline with attention-weighted multiple instance learning (attMIL) to predict HRD status from histology images. As part of our approach, we calculated a genomic scar HRD score by combining loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST) from whole genome sequencing (WGS) data of n = 5209 patients across two independent cohorts. The model’s effectiveness was evaluated using the area under the receiver operating characteristic curve (AUROC), focusing on its accuracy in predicting genomic HRD against a clinically recognized cutoff value.

Results

Our study demonstrated the predictability of genomic HRD status in endometrial, pancreatic, and lung cancers reaching cross-validated AUROCs of 0.79, 0.58, and 0.66, respectively. These predictions generalized well to an external cohort, with AUROCs of 0.93, 0.81, and 0.73. Moreover, a breast cancer-trained image-based HRD classifier yielded an AUROC of 0.78 in the internal validation cohort and was able to predict HRD in endometrial, prostate, and pancreatic cancer with AUROCs of 0.87, 0.84, and 0.67, indicating that a shared HRD-like phenotype occurs across these tumor entities.

Conclusions

This study establishes that HRD can be directly predicted from H&E slides using attMIL, demonstrating its applicability across nine different tumor types.
The efficacy of different biomarkers and endpoints to refine referrals for suspected prostate cancer: the TARGET study (Tiered integrAted tests for eaRly diaGnosis of clinically significant ProstatE Tumours)
Authors: Lophatananon Artitaya , Muir Kenneth R. , Gnanapragasam Vincent J.
Published: October 2024

Background

The majority of men referred with a raised PSA for suspected prostate cancer will receive unnecessary tertiary investigations including MRI and biopsy. Here, we compared different types of biomarkers to refine tertiary referrals and when different definitions of clinically significant cancer were used.

Methods

Data and samples from 798 men referred for a raised PSA (≥ 3 ng/mL) and investigated through an MRI-guided biopsy pathway were accessed for this study. Bloods were acquired pre-biopsy for liquid biomarkers and germline DNA. Variables explored included PSA + Age (base model), free/total PSA (FTPSA), Prostate Health Index (phi), PSA density (PSAd), polygenic risk score (PRS) and MRI (≥ LIKERT 3). Different diagnostic endpoints for significant cancer (≥ grade group 2 [GG2], ≥ GG3, ≥ Cambridge Prognostic Group 2 [CPG2], ≥ CPG3) were tested. The added value of each biomarker to the base model was evaluated using logistic regression models, AUC and decision curve analysis (DCA) plots.

Results

The median age and PSA was 65 years and 7.13 ng/mL respectively. Depending on definition of clinical significance, ≥ grade group 2 (GG2) was detected in 57.0% (455/798), ≥ GG3 in 27.5% (220/798), ≥ CPG2 in 61.6% (492/798) and ≥ CPG3 in 42.6% (340/798). In the pre-MRI context, the PSA + Age (base model) AUC for prediction of ≥ GG2, ≥ GG3, ≥ CPG2 and ≥ CPG3 was 0.66, 0.68, 0.70 and 0.75 respectively. Adding phi and PSAd to base model improved performance across all diagnostic endpoints but was notably better when the composite CPG prognostic score was used: AUC 0.82, 0.82, 0.83, 0.82 and AUC 0.74, 0.73, 0.79, 0.79 respectively. In contrast, neither FTPSA or PRS scores improved performance especially in detection of ≥ GG3 and ≥ CPG3 disease. Combining biomarkers did not alter results. Models using phi and PSAd post-MRI also improved performances but again benefit varied with diagnostic endpoint. In DCA analysis, models which incorporated PSAd and phi in particular were effective at reducing use of MRI and/or biopsies especially for ≥ CPG3 disease.

Conclusion

Incorporating phi or PSAd can refine and tier who is referred for tertiary imaging and/or biopsy after a raised PSA test. Incremental value however varied depending on the definition of clinical significance and was particularly useful when composite prognostic endpoints are used.
Monitoring the efficiency of reversal on anti-Xa direct oral anticoagulants using point-of-care viscoelastic testing
Authors: Heubner Lars , Grottke Oliver , Vicent Oliver , Spieth Peter Markus , Beyer-Westendorf Jan
Published: October 2024

Bleeding events in patients receiving direct oral anticoagulation (DOAC) can be life-threatening even at therapeutic DOAC plasma concentrations, as anticoagulation impairs hemostasis and should therefore be identified immediately after hospital admission. The anticoagulatory effects of DOAC are typically not measurable in standard coagulation tests, such as PT or aPTT. Specific calibrated anti-FXa-tests allow specific drug monitoring, but they are too time-consuming for critical bleeding events and are commonly not available for 24 h/7 days in routine care. However, recent advances in point-of-care (POC) viscoelastic testing (VET) have shown a promising approach for rapid and quantitative detection of DOAC plasma concentrations using the Russell viper venom factor V activator (RVV for FXa-inhibitors) test or the ecarin clotting time (thrombin inhibitors). In acute bleeding situations, direct FXa inhibitors can be reversed by specific antidote andexanet alfa or hemostasis can be improved by prothrombin complex factor concentrates (PCCs). After reversal, confirmation of reversal efficacy is often requested, but no routine assays are currently available. Thus, the emergency management of bleeding DOAC patients is usually “blinded” with regard to reversal efficacy. POC VET laboratory assays might therefore also be helpful for measuring DOAC effects after reversal. We present a case series demonstrating the usefulness of RVV-clotting time post-DOAC reversal with andexanet alfa.
A pilot study of the cardiopulmonary effects in healthy volunteers after exposure to high levels of PM2.5 in a New York City subway station
Authors: Luglio David G. , Farrell Kayla Rae , Gordon Terry
Published: October 2024

Background

Subway systems are becoming increasingly common worldwide transporting large populations in major cities. PM2.5 concentrations have been demonstrated to be exceptionally high when underground, however. Studies on the impact of subway PM exposure on cardiopulmonary health in the United States are limited.

Methods

Healthy volunteers in New York City were exposed to a 2-h visit on the 9th Street Station platform on the Port Authority Trans-Hudson train system. Blood pressure, heart rate variability (HRV), spirometry, and forced impulse oscillometry were measured, and urine, blood spot, and nasal swab biosamples were collected for cytokine analysis at the end of the 2-h exposure period. These endpoints were compared against individual control measurements collected after 2-h in a “clean” control space. In addition to paired comparisons, mixed effects models with subject as a random effect were employed to investigate the effect of the PM2.5 concentrations and visit type (i.e., subway vs. control).

Results

Mean PM2.5 concentrations on the platform and during the control visit were 293.6 ± 65.7 (SD) and 4.6 ± 1.9 µg/m3, respectively. There was no change in any of the health metrics, but there was a non-significant trend for SDNN to be lower after subway exposure compared to control exposure. Total symptomatic scores did increase post-subway exposure compared to reported values prior to exposure or after the control visit. No significant changes in cytokine concentrations in any specimen type were observed. Mixed-effects models mostly corroborated these paired comparisons.

Conclusions

Acute exposures to PM on a subway platform do not cause measurable cardiopulmonary effects apart from reductions in HRV and increases in symptoms in healthy volunteers. These findings match other studies that found little to no changes in lung function and blood pressure after exposure in underground subway stations. Future work should still target potentially more vulnerable populations, such as individuals with asthma or those who spend increased time underground on the subway such as transit workers.
Nanopore sequencing with unique molecular identifiers enables accurate mutation analysis and haplotyping in the complex lipoprotein(a) KIV-2 VNTR
Authors: Amstler Stephan , Streiter Gertraud , Pfurtscheller Cathrin , Forer Lukas , Di Maio Silvia , Weissensteiner Hansi , Paulweber Bernhard , Schönherr Sebastian , Kronenberg Florian , Coassin Stefan
Published: October 2024

Background

Repetitive genome regions, such as variable number of tandem repeats (VNTR) or short tandem repeats (STR), are major constituents of the uncharted dark genome and evade conventional sequencing approaches. The protein-coding LPA kringle IV type-2 (KIV-2) VNTR (5.6 kb per unit, 1–40 units per allele) is a medically highly relevant example with a particularly intricate structure, multiple haplotypes, intragenic homologies, and an intra-VNTR STR. It is the primary regulator of plasma lipoprotein(a) [Lp(a)] concentrations, an important cardiovascular risk factor. Lp(a) concentrations vary widely between individuals and ancestries. Multiple variants and functional haplotypes in the LPA gene and especially in the KIV-2 VNTR strongly contribute to this variance.

Methods

We evaluated the performance of amplicon-based nanopore sequencing with unique molecular identifiers (UMI-ONT-Seq) for SNP detection, haplotype mapping, VNTR unit consensus sequence generation, and copy number estimation via coverage-corrected haplotypes quantification in the KIV-2 VNTR. We used 15 human samples and low-level mixtures (0.5 to 5%) of KIV-2 plasmids as a validation set. We then applied UMI-ONT-Seq to extract KIV-2 VNTR haplotypes in 48 multi-ancestry 1000 Genome samples and analyzed at scale a poorly characterized STR within the KIV-2 VNTR.

Results

UMI-ONT-Seq detected KIV-2 SNPs down to 1% variant level with high sensitivity, specificity, and precision (0.977 ± 0.018; 1.000 ± 0.0005; 0.993 ± 0.02) and accurately retrieved the full-length haplotype of each VNTR unit. Human variant levels were highly correlated with next-generation sequencing (R2 = 0.983) without bias across the whole variant level range. Six reads per UMI produced sequences of each KIV-2 unit with Q40 quality. The KIV-2 repeat number determined by coverage-corrected unique haplotype counting was in close agreement with droplet digital PCR (ddPCR), with 70% of the samples falling even within the narrow confidence interval of ddPCR. We then analyzed 62,679 intra-KIV-2 STR sequences and explored KIV-2 SNP haplotype patterns across five ancestries.

Conclusions

UMI-ONT-Seq accurately retrieves the SNP haplotype and precisely quantifies the VNTR copy number of each repeat unit of the complex KIV-2 VNTR region across multiple ancestries. This study utilizes the KIV-2 VNTR, presenting a novel and potent tool for comprehensive characterization of medically relevant complex genome regions at scale.
Increase in PVC-BSI during the second COVID-19 pandemic year: analysis of catheter and patient characteristics
Authors: Pianca Eva , Zanella Marie-Céline , Obama Basilice Minka , Nguyen Aude , Fortchantre Loïc , Chraiti Marie-Noëlle , Harbarth Stephan , Catho Gaud , MacPhail Aleece , Buetti Niccolò
Published: October 2024

Background

Increasing nosocomial infections during the COVID-19 pandemic have been reported. However, data describing peripheral venous catheter associated bloodstream infections (PVC-BSI) are limited.

Aims

To describe the epidemiology and risk factors for PVC-BSI during the COVID-19 pandemic.

Methods

We conducted retrospective cohort study of prospectively collected PVC-BSI data in a 2100 bed hospital network in Switzerland. Adult patients with a PVC inserted between January 1, 2020 and December 31, 2021 were included. Risk factors for PVC-BSI were identified through descriptive analysis of patient and catheter characteristics, and univariable marginal Cox models.

Results

206,804 PVCs and 37 PVC-BSI were analysed. Most PVC-BSI were attributed to catheters inserted in the Emergency department (76%) or surgical wards (22%). PVC-BSI increased in 2021 compared to 2020 (hazard ratio 2021 vs. 2020 = 2.73; 95% confidence interval 1.19–6.29), with a numerically higher rate of Staphylococcus aureus (1/10, 10%, vs. 5/27, 19%) and polymicrobial infection (0/10, 0% vs. 4/27, 15%). PVC insertions, patient characteristics, and catheter characteristics remained similar across the study period. PVC-BSI risk was associated with admission to the intensive care unit (ICU), and use of wide gauge catheter ( < = 16G).

Conclusion

Increased PVC-BSI during the COVID-19 pandemic was not explained by catheter or patient factors alone, and may result from system-wide changes. PVC-BSI events are primarily attributed to acute care settings, including the emergency department, surgical wards, and the ICU.
Global burden of viral infectious diseases of poverty based on Global Burden of Diseases Study 2021
Authors: Li Xin-Chen , Zhang Yan-Yan , Zhang Qi-Yu , Liu Jing-Shu , Ran Jin-Jun , Han Le-Fei , Zhang Xiao-Xi
Published: October 2024

Background

Viral infectious diseases of poverty (vIDPs) remain a significant global health challenge. Despite their profound impact, the burden of these diseases is not comprehensively quantified. This study aims to analyze the global burden of six major vIDPs, including coronavirus disease 2019 (COVID-19), HIV/AIDS, acute hepatitis, dengue, rabies, and Ebola virus disease (EVD), using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021).

Methods

Following the GBD 2021 framework, we analyzed the incidence, mortality, and disability-adjusted life years (DALYs) of the six vIDPs across 204 countries and territories from 1990 to 2021. We examined the association between the Socio-Demographic Index (SDI) and the burden of vIDPs. All estimates were reported as numbers and rates per 100,000 population, calculated using the Bayesian statistical model employed by GBD 2021, with 95% uncertainty intervals (UI).

Results

In 2021, vIDPs caused approximately 8.7 million deaths and 259.2 million DALYs, accounting for 12.8% and 9.0% of the global all-cause totals, respectively. Globally, the burden of vIDPs varied significantly: COVID-19 caused around 7.9 million (95% UI: 7.5, 8.4) deaths and 212.0 million (95% UI 197.9, 234.7) DALYs in 2021. Acute hepatitis had the second-highest age-standardized incidence rate, with 3411.5 (95% UI: 3201.8, 3631.3) per 100,000 population, while HIV/AIDS had a high age-standardized prevalence rate, with 483.1 (95% UI: 459.0, 511.4) per 100,000 population. Dengue incidence cases rose from 26.5 million (95% UI: 3.9, 51.9) in 1990 to 59.0 million (95% UI: 15.5, 106.9) in 2021. Rabies, although reduced in prevalence, continued to pose a significant mortality risk. EVD had the lowest overall burden but significant outbreak impacts. Age-standardized DALY rates for vIDPs were significantly negatively correlated with SDI: acute hepatitis (r = −0.8, P < 0.0001), rabies (r = −0.7, P < 0.0001), HIV/AIDS (r = −0.6, P < 0.0001), COVID-19 (r = −0.5, P < 0.0001), dengue (r = −0.4, P < 0.0001), and EVD (r = −0.2, P < 0.005).

Conclusions

VIDPs pose major public health challenges worldwide, with significant regional, age, and gender disparities. The results underscore the need for targeted interventions and international cooperation to mitigate the burden of these diseases. Policymakers can use these findings to implement cost-effective interventions and improve health outcomes, particularly in regions with high or increasing burdens.
Evaluation of the therapeutic potential of novel nanoparticle formulations of glutathione and virgin coconut oil in an experimental model of carbon tetrachloride-induced liver failure
Authors: Allam Essmat A. H. , Darwish Madeha H. A. , Abou Khalil Nasser S. , El-Baset Shimaa H. A. Abd , El-Aal Mohamed Abd , Elrawy Ahmed , Ahmed Ahmed A. N. , Sabra Mahmoud S.
Published: October 2024

Background

Acute liver failure (ALF) is a critical condition characterized by rapid liver dysfunction, leading to high mortality rates. Current treatments are limited, primarily supportive, and often require liver transplantation. This study investigates the potential of a novel nanoparticle formulation of glutathione (GSH) and virgin coconut oil (VCO) alone and in combination to enhance therapeutic outcomes in a rat model of ALF induced by orogastric carbon tetrachloride (CCl4).

Methods

The study employed adult male Albino rats divided into ten groups, with ALF induced via a single oral dose of CCl4. Various treatment regimens were administered over seven days, including conventional and nanoparticle forms of GSH and VCO and their combinations. The efficacy of treatments was evaluated through biochemical analysis of liver function markers, oxidative stress indicators, inflammatory biomarkers, and histopathological examinations. Nanoparticles were synthesized using established methods, and characterization techniques were employed to ensure their quality and properties.

Results

The nanoparticle formulations significantly improved liver function, as indicated by reduced serum levels of alanine aminotransferase and aspartate aminotransferase, alongside decreased oxidative stress markers such as malondialdehyde. Furthermore, they reduced tumor necrosis factor alpha and interleukin-1 beta inflammatory markers. Histological analysis revealed reduced hepatocellular necrosis and inflammation in treated groups compared to controls. Also, decreased nuclear factor-kappa B was detected by immunohistochemical analysis.

Conclusion

The findings show that the nanoparticle mixture of GSH and VCO effectively reduces liver damage in ALF. This suggests a promising drug-based approach for improving liver regeneration and protection. This innovative strategy may pave the way for new therapeutic interventions in the management of ALF.
An efficient and easy-to-use protocol for induction of haploids in cucumber through parthenogenic embryo development
Authors: N Pradeepkumara , Parkash Chander , Bhatia Reeta , Munshi Anilabha Das , Rao Mahesh , Subhasmita Subhashree , Behera Tusar Kanti , Dey Shyam Sundar
Published: October 2024

Background

Cucumber (Cucumis sativus L.) is a model crop to study cell biology, including the development of haploids and doubled haploids in vegetable crops. In plant breeding, haploid and doubled haploids are valuable tools for developing pure homozygous inbred lines and accelerating genetic progress by reducing the time required for breeding cycles. Besides, the haploids are also valuable in genomic studies. We are reporting the induction of haploids in cucumber involving gynoecious and parthenocarpic genotypes for the first time. This study aimed to assess the efficient induction of haploids through pollination with gamma-irradiated pollen in cucumber. The effect of gamma irradiation dose on pollen viability and germination, fruit setting percentage, seed development, and haploid embryo development in cucumber hybrid genotypes were studied in detail. The goal was to utilize this information to produce haploid plants for genomics and transformation works in this model vegetable crop.

Results

Pollination was done on six cucumber genotypes using varying doses of gamma rays (100, 200, 300, 400, and 500 Gy). Genotypes, doses of irradiation, and embryo developmental stage influenced the successful generation of in-vitro haploid plants. The optimal timeframe for embryo rescue was found to be 25 to 30 days after pollination. Haploid embryos were effectively induced using irradiated pollen at 400 to 500 Gy doses. Parthenogenetic plantlets were analyzed, and their ploidy level was confirmed through stomatal physiology, cytology (mitosis), and flow cytometry methods.

Conclusion

Through parthenogenic embryo development, it is possible to induce a large number of haploids in cucumber. This technique’s power lies in its ability to streamline the breeding process, enhance genetic gain, and produce superior cultivars that contribute to sustainable agriculture and food security.
Effects of normal saline versus lactated Ringer’s solution on organ function and inflammatory responses to heatstroke in rats
Authors: Chen Lan , Liu Chang , Zhang Zhaocai , Zhang Yuping , Feng Xiuqin
Published: October 2024

Background

Heatstroke is a life-threatening condition characterized by severe hyperthermia and multiple organ dysfunction. Both normal saline (NS) and lactated Ringer’s solution (LR) are commonly used for cooling and volume resuscitation in heatstroke patients; however, their specific impacts on patient outcomes during heatstroke management are poorly understood. Given that the systemic inflammatory response and multiple-organ damage caused by heat toxicity are the main pathophysiological features of heatstroke, the aim of this study was to evaluate the effects of NS and LR on the production of inflammatory cytokines and the functional and structural integrity of renal and cardiac tissues in a rat model of heatstroke.

Methods

Fifty-five male Sprague‒Dawley rats were randomly divided into four groups: cold NS or LR infusion postheatstroke (4 ℃, 4 ml/100 g, over 10 min) and NS or LR infusion without heatstroke induction (control groups). Vital signs, arterial blood gases, inflammatory cytokines, and renal and cardiac function indicators, such as serum creatinine and cTnI, were monitored after treatment. Tissue samples were analysed via HE staining, electron microscopy, and fluorescence staining for apoptosis markers, and protein lysates were used for Western blotting of pyroptosis-related proteins.

Results

Compared with LR-treated heatstroke rats, NS-treated heatstroke rats presented lower mean arterial pressures, worsened metabolic acidosis, and higher levels of IL-6 and TNF-α in both the serum and tissue. These rats also presented increased serum creatinine, troponin, catecholamines, and NGAL and reduced renal clearance. Histological and ultrastructural analyses revealed more severe tissue damage in NS-treated rats, with increased apoptosis and increased expression of NLRP3/caspase-1/GSDMD signalling molecules. Similar differences were not observed between the control groups receiving either NS or LR infusion. One NS-treated heatstroke rat died within 24 h, whereas all the LR-treated and control rats survived.

Conclusions

NS resuscitation in heat-exposed rats significantly promotes metabolic acidosis and the inflammatory response, leading to greater functional and structural organ damage than does LR. These findings underscore the necessity of selecting appropriate resuscitation fluids for heatstroke management to minimize organ damage and improve outcomes.
RAS mutant transverse colon cancer with multiple liver metastases achieving long-term disease-free survival with postoperative maintenance therapy with aflibercept + FOLFIRI and four repeated radical resections: a case report
Authors: Tanaka Yasushi , Nakanishi Ryota , Sato Shota , Otake Akihiko , Ryujin Keiichiro , Ikeda Shinichiro , Ebata Yuho , Harima Tomoya , Natsugoe Keita , Yoshiyama Takayuki , Shin Yuki , Kawazoe Tetsuro , Kudo Kensuke , Zaitsu Yoko , Hisamatsu Yuichi , Ando Koji , Nakashima Yuichiro , Itoh Shinji , Oki Eiji , Oda Yoshinao , Yoshizumi Tomoharu
Published: October 2024

Background

Management of patients with colorectal liver metastases (CRLMs) requires a multidisciplinary approach. For patients with progression of RAS mutant tumors, the choice of angiogenesis inhibitors can be controversial. Here, we report a patient with RAS mutant CRLMs achieving long-term disease-free survival with repeated R0 resections and perioperative treatment, especially aflibercept + FOLFIRI (5-fluorouracil, levofolinate, irinotecan), which may have prevented long-term recurrence.

Case presentation

The patient was a 37 year-old woman diagnosed with RAS mutant transverse colon cancer with 19 LMs. As the metastases were limited to the liver, we introduced systemic chemotherapy aiming at conversion surgery. After six cycles of bevacizumab + FOLFOXIRI (5-fluorouracil, levofolinate, oxaliplatin, irinotecan), we performed partial hepatectomy for all LMs, and left hemicolectomy for the primary tumor after another four cycles of bevacizumab + FOLFIRI. Three months after surgery, the patient presented with massive ovarian metastases with carcinomatous ascites. We conducted bilateral oophorectomy, and initiated aflibercept + FOLFIRI therapy considering the possibility of resistance to bevacizumab. The patient was recurrence-free for 2 years during aflibercept + FOLFIRI treatment. After its discontinuation, two distant metastases developed. Both were resectable and the patient achieved recurrence-free survival of 2 years and 3 months after the last operation (6 years since initiation of treatment), without additional chemotherapy.

Conclusions

We believe that multidisciplinary treatment aimed at complete resection could lead to long-term survival even in patients with repeated recurrence of CRLMs. Aflibercept + FOLFIRI could be effective in controlling metastasis of RAS mutant colon cancer even after treatment with bevacizumab.
Agreement Between Heart Rate Variability - Derived vs. Ventilatory and Lactate Thresholds: A Systematic Review with Meta-Analyses
Authors: Tanner Valérian , Millet Grégoire P. , Bourdillon Nicolas
Published: October 2024

Background

Determining thresholds by measuring blood lactate levels (lactate thresholds) or gas exchange (ventilatory thresholds) that delineate the different exercise intensity domains is crucial for training prescription. This systematic review with meta-analyses aims to assess the overall validity of the first and second heart rate variability - derived threshold (HRVT1 and HRVT2, respectively) by computing global effect sizes for agreement and correlation between HRVTs and reference – lactate and ventilatory (LT-VTs) – thresholds. Furthermore, this review aims to assess the impact of subjects’ characteristics, HRV methods, and study protocols on the agreement and correlation between LT-VTs and HRVTs.

Methods

Systematic computerised searches for studies determining HRVTs during incremental exercise in humans were conducted. The agreements and correlations meta-analyses were conducted using a random-effect model. Causes of heterogeneity were explored by subgroup analysis and meta-regression with subjects’ characteristics, incremental exercise protocols, and HRV methods variables. The methodological quality was assessed using QUADAS-2 and STARDHRV tools. The risk of bias was assessed by funnel plots, fail-safe N test, Egger’s test of the intercept, and the Begg and Mazumdar rank correlation test.

Results

Fifty included studies (1160 subjects) assessed 314 agreements (95 for HRVT1, 219 for HRVT2) and 246 correlations (82 for HRVT1, 164 for HRVT2) between LT-VTs and HRVTs. The standardized mean differences were trivial between HRVT1 and LT1-VT1 (SMD = 0.08, 95% CI -0.04–0.19, n = 22) and between HRVT2 and LT2-VT2 (SMD = -0.06, 95% CI -0.15–0.03, n = 42). The correlations were very strong between HRVT1 and LT1-VT1 (r = 0.85, 95% CI 0.75–0.91, n = 22), and between HRVT2 and LT2-VT2 (r = 0.85, 95% CI 0.80–0.89, n = 41). Moreover, subjects’ characteristics, type of ergometer, or initial and incremental workload had no impact on HRVTs determination.

Conclusion

HRVTs showed trivial differences and very strong correlations with LT-VTs and might thus serve as surrogates. These results emphasize the usefulness of HRVTs as promising, accessible, and cost-effective means for exercise and clinical prescription purposes.