bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovative and disruptive technologies to prescribe, encourage, and evaluate physical exercise in healthy adults: a protocol of exploratory study followed by a noninferiority, investigator-blinded randomized clinical trial
Authors: Loro Fernanda Laís , Martins Riane , de Araújo Cintia Laura Pereira , Prade Lucio Rene , do Rosário Denis Lima , da Rocha Seruffo Marcos César , de Freitas Italo Adriano Moraes , Nobre Jéferson , Both Cristiano Bonato , Dal Lago Pedro
Published: October 2023

Background

Cardiovascular diseases are a leading cause of mortality worldwide. A significant contributing factor to this mortality is the lack of engagement in preventive activities. Consequently, strategies for enhancing adherence to and duration of physical activity (PA) have become pivotal. This project aims to create and validate innovative, disruptive, and secure technologies that ensure appropriate exercise intensity, bolster adherence to PA, and monitor health biomarker responses pre-, during, and post-physical activity.

Methods

This exploratory study, followed by a noninferiority, investigator-blinded randomized clinical trial, will be divided into three phases: (1) development and validation of a sensor for real-time biofeedback during a functional assessment test; (2) integration of biofeedback and gamification into an app for the structured prescription of physical training within a controlled setting; and (3) implementation of biofeedback and gamification into an app for the prescription and monitoring of physical training in an uncontrolled setting. Phase 1 entails a validation test of a biosensor—monitoring heart rate (HR) and steps—during a modified shuttle walk test. In phase 2, the biosensor interfaces with a gamified smartphone application. The training regimen spans 6 weeks, 5 days weekly, with each session lasting 60 min: a five-min warm-up involving stationary gait, followed by 50 min of training at the target HR on the step and concluding with a five-min cool-down at a stationary pace. After 6 weeks of training, a new functional capacity test is conducted. Phase 3 involves an investigator-blinded, randomized clinical trial to demonstrate noninferiority. Participants are randomly assigned to either the intervention group (IG) or the control group (CG). IG participants practice exercise using the gamified application in an uncontrolled environment according to the prescribed method outlined in phase 2. CG participants receive PA practice guidelines exclusively.

Discussion

Anticipated outcomes include improved exercise adherence through the gamified application, better maintenance of prescribed exercise intensity, and enhanced health biomarkers. The results of this study will inform health-related decision-making.

Trial registration

The study protocol received approval from the Ethics Committee of Universidade Federal de Ciências da Saúde de Porto Alegre (54,492,221.80000.5345) and has been registered with the Brazilian Registry of Clinical Trials (ReBEC, RBR-359p69v).
Biochemical and structural characterization of a glucan synthase GFGLS2 from edible fungus Grifola frondosa to synthesize β-1, 3-glucan
Authors: Yang Yu-Meng , Fu Xin , Cui Feng-Jie , Sun Lei , Zan Xin-Yi , Sun Wen-Jing
Published: October 2023

Background

Grifola frondosa is a Basidiomycete fungus belonging to the family of Grifolaceae and the order of Polyporales. β-Glucans are the main polymers in G. frondosa, playing a crucial role in the physiology and representing the healthy benefits for humans. The membrane-integrated β-1, 3-glucan synthase (GLS) is responsible for glucan synthesis, cell wall assembly, differentiation and growth of the edible fungi. However, the structural/catalytic characteristics and mechanisms of β-1, 3-glucan synthases in G. frondosa are still unknown due to their extremely complex structures with multi-transmembranes and large molecular masses.

Results

Herein, a β-1, 3-glucan synthase (GFGLS2) was purified and identified from the cultured mycelia with a specific activity of 60.01 pmol min−1 μg−1 for the first time. The GFGLS2 showed a strict specificity to UDP-glucose with a Vmax value of 1.29 ± 0.04 µM min−1 at pH 7.0 and synthesized β-1, 3-glucan with a maximum degree of polymerization (DP) of 62. Sequence Similarity Network (SSN) analysis revealed that GFGLS2 has a close relationship with others in Ganoderma sinense, Trametes coccinea, Polyporus brumalis, and Trametes pubescens. With the assistance of 3D structure modelling by AlphaFold 2, molecular docking and molecular dynamics simulations, the central hydrophilic domain (Class III) in GFGLS2 was the main active sites through binding the substrate UDP–glucose to 11 amino acid residues via hydrogen bonds, π-stacking and salt bridges.

Conclusions

The biochemical, 3D structural characterization and potential catalytic mechanism of a membrane-bound β-1, 3-glucan synthase GFGLS2 from cultured mycelia of G. frondosa were well investigated and would provide a reasonable full picture of β-1, 3-glucan synthesis in fungi.
Bacterial genome-wide association study substantiates papGII of Escherichia coli as a major risk factor for urosepsis
Authors: Cuénod Aline , Agnetti Jessica , Seth-Smith Helena M. B. , Roloff Tim , Wälchli Denise , Shcherbakov Dimitri , Akbergenov Rashid , Tschudin-Sutter Sarah , Bassetti Stefano , Siegemund Martin , Nickel Christian H. , Moran-Gilad Jacob , Keys Timothy G. , Pflüger Valentin , Thomson Nicholas R. , Egli Adrian
Published: October 2023

Background

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, often caused by uropathogenicEscherichia coli. Multiple bacterial virulence factors or patient characteristics have been linked separately to progressive, more invasive infections. In this study, we aim to identify pathogen- and patient-specific factors that drive the progression to urosepsis by jointly analysing bacterial and host characteristics.

Methods

We analysed 1076E. colistrains isolated from 825 clinical cases with UTI and/or bacteraemia by whole-genome sequencing (Illumina). Sequence types (STs) were determined via srst2 and capsule loci via fastKaptive. We compared the isolates from urine and blood to confirm clonality. Furthermore, we performed a bacterial genome-wide association study (bGWAS) (pyseer) using bacteraemia as the primary clinical outcome. Clinical data were collected by an electronic patient chart review. We concurrently analysed the association of the most significant bGWAS hit and important patient characteristics with the clinical endpoint bacteraemia using a generalised linear model (GLM). Finally, we designed qPCR primers and probes to detectpapGII-positiveE. colistrains and prospectively screenedE. colifrom urine samples (n = 1657) at two healthcare centres.

Results

Our patient cohort had a median age of 75.3 years (range: 18.00–103.1) and was predominantly female (574/825, 69.6%). The bacterial phylogroups B2 (60.6%; 500/825) and D (16.6%; 137/825), which are associated with extraintestinal infections, represent the majority of the strains in our collection, many of which encode a polysaccharide capsule (63.4%; 525/825). The most frequently observed STs were ST131 (12.7%; 105/825), ST69 (11.0%; 91/825), and ST73 (10.2%; 84/825). Of interest, in 12.3% (13/106) of cases, theE. colipairs in urine and blood were only distantly related. In line with previous bGWAS studies, we identified the genepapGII(p-value < 0.001), which encodes the adhesin subunit of theE. coliP-pilus, to be associated with ‘bacteraemia’ in our bGWAS. In our GLM, correcting for patient characteristics,papGIIremained highly significant (odds ratio = 5.27, 95% confidence interval = [3.48, 7.97],p-value < 0.001). An independent cohort of cases which we screened forpapGII-carryingE. coliat two healthcare centres further confirmed the increased relative frequency ofpapGII-positive strains causing invasive infection, compared topapGII-negative strains (p-value = 0.033, chi-squared test).

Conclusions

This study builds on previous work linkingpapGIIwith invasive infection by showing that it is a major risk factor for progression from UTI to bacteraemia that has diagnostic potential.
Polygenic risk scores for disease risk prediction in Africa: current challenges and future directions
Authors: Fatumo Segun , Sathan Dassen , Samtal Chaimae , Isewon Itunuoluwa , Tamuhla Tsaone , Soremekun Chisom , Jafali James , Panji Sumir , Tiffin Nicki , Fakim Yasmina Jaufeerally
Published: October 2023

Early identification of genetic risk factors for complex diseases can enable timely interventions and prevent serious outcomes, including mortality. While the genetics underlying many Mendelian diseases have been elucidated, it is harder to predict risk for complex diseases arising from the combined effects of many genetic variants with smaller individual effects on disease aetiology. Polygenic risk scores (PRS), which combine multiple contributing variants to predict disease risk, have the potential to influence the implementation for precision medicine. However, the majority of existing PRS were developed from European data with limited transferability to African populations. Notably, African populations have diverse genetic backgrounds, and a genomic architecture with smaller haplotype blocks compared to European genomes. Subsequently, growing evidence shows that using large-scale African ancestry cohorts as discovery for PRS development may generate more generalizable findings. Here, we (1) discuss the factors contributing to the poor transferability of PRS in African populations, (2) showcase the novel Africa genomic datasets for PRS development, (3) explore the potential clinical utility of PRS in African populations, and (4) provide insight into the future of PRS in Africa.
Aerobic exercise and metformin on intermuscular adipose tissue (IMAT): insights from multimodal MRI and histological changes in prediabetic rats
Authors: Yu Fuyao , Xing Chuan , Fan Yiping , Liu Yanping , Su Peng , Yang Qiuhua , Dong Yanbin , Hou Yang , Pan Shinong
Published: October 2023

Background

Physical exercise is the first-line intervention for prediabetes, and metformin is the most widely used oral insulin-sensitizing agent. Moreover, intermuscular adipose tissue (IMAT) directly affects insulin resistance by helping maintain glucose homeostasis. Here, we evaluated the effects of moderate aerobic exercise and/or metformin on histological IMAT parameters in non-streptozotocin-induced prediabetes.

Methods

Male Wistar rats with prediabetes fed a high-fat diet and high-sugar drinks were randomly assigned to high-fat diet (PRE), metformin (MET), moderate aerobic exercise (EXE), combined therapy (EMC), or EMC + compound-c (EMA) groups for 4 weeks. Multimodal magnetic resonance imaging (MRI) was then performed, and tissue-specific inflammation and energy and lipid metabolism were evaluated in IMAT.

Results

The EXE group had lower inflammatory factor levels, lipid metabolism, and mitochondrial oxidative stress, and shorter IMAT adipocyte diameters than the MET group. The MET group exhibited lower IL-1β and Plin5 expression than the PRE group. Furthermore, the IMAT of the EMC group had lower TNF-α and phosphorylated NF-κB levels and higher GLUT1 and GLUT4 expression than the PRE group. Multimodal MRI revealed significant changes in transverse-relaxation time 2, apparent diffusion coefficient, and fractional anisotropy values in the IMAT and muscles, as well as lower IMAT% values in the EXE and EMC groups than in the MET and PRE groups.

Conclusion

Moderate aerobic exercise training can effectively improve IMAT function and structure via the AMP-activated protein kinase pathway in prediabetes. Combining metformin with moderate aerobic exercise might elicit modest synergy, and metformin does not counterbalance the beneficial effects of exercise.
The immune-adjunctive potential of recombinant LAB vector expressing murine IFNλ3 (MuIFNλ3) against Type A Influenza Virus (IAV) infection
Authors: Yadav Sandeep , Varma Aparna , Muralidharan Aparna Odayil , Bhowmick Sucharita , Mondal Samiran , Mallick Amirul Islam
Published: October 2023

Background

The conventional means of controlling the recurring pandemics of Type A Influenza Virus (IAV) infections remain challenging primarily because of its high mutability and increasing drug resistance. As an alternative to control IAV infections, the prophylactic use of cytokines to drive immune activation of multiple antiviral host factors has been progressively recognized. Among them, Type III Interferons (IFNs) exhibit a pivotal role in inducing potent antiviral host responses by upregulating the expression of several antiviral genes, including the Interferon-Stimulated Genes (ISGs) that specifically target the virus replication machinery. To harness the immuno-adjunctive potential, we examined whether pre-treatment of IFNλ3, a Type III IFN, can activate antiviral host responses against IAV infections.

Methods

In the present study, we bioengineered a food-grade lactic acid-producing bacteria (LAB), Lactococcus lactis (L. lactis), to express and secrete functional murine IFNλ3 (MuIFNλ3) protein in the extracellular milieu. To test the immune-protective potential of MuIFNλ3 secreted by recombinant L. lactis (rL. lactis), we used murine B16F10 cells as an in vitro model while mice (BALB/c) were used for in vivo studies.

Results

Our study demonstrated that priming with MuIFNλ3 secreted by rL. lactis could upregulate the expression of several antiviral genes, including Interferon Regulatory Factors (IRFs) and ISGs, without exacerbated pulmonary or intestinal inflammatory responses. Moreover, we also showed that pre-treatment of B16F10 cells with MuIFNλ3 can confer marked immune protection against mice-adapted influenza virus, A/PR/8/1934 (H1N1) infection.

Conclusion

Since the primary target for IAV infections is the upper respiratory and gastrointestinal tract, immune activation without affecting the tissue homeostasis suggests the immune-adjunctive potential of IFNλ3 against IAV infections.
Training items for trainee residents in community medicine in rural areas
Authors: Kumabe Ayako , Kenzaka Tsuneaki , Mizutani Naoya , Goda Ken , Yahata Shinsuke
Published: October 2023

Objective

To examine the significant events experienced by initial trainees during community medicine training, evaluate their impact on community medicine practice, and support improvements in rural community medicine training.

Results

Three faculty teachers independently evaluated the reports of 25 residents who had completed a four-week community medicine training in a rural area to analyze major events. The reports were analyzed using topics from the Model Core Curriculum for Medical Education that relate to rural medicine. The most frequently reported items were identified as follows: Primary care: 9 (36.0%); integrated community care systems: 8 (32.0%); medical care in the local community: 7 (28.0%); home health care and systems, patient-physician relationship, and end-of-life medical treatment and care: 6 each (24.0%). Reports from residents describing events related to home health care and systems and end-of-life medical treatment and care were related to more than one item.
Blockade of adenosine A2A receptors reverses early spatial memory defects in the APP/PS1 mouse model of Alzheimer’s disease by promoting synaptic plasticity of adult-born granule cells
Authors: Ji Qi , Yang Yang , Xiong Yun , Zhang Ying-Jie , Jiang Jun , Zhou Li-Ping , Du Xiao-Hui , Wang Chun-Xiang , Zhu Zhi-Ru
Published: October 2023

Background

The over-activation of adenosine A2A receptors (A2AR) is closely implicated in cognitive impairments of Alzheimer's disease (AD). Growing evidence shows that A2AR blockade possesses neuroprotective effects on AD. Spatial navigation impairment is an early manifestation of cognitive deficits in AD. However, whether A2AR blockade can prevent early impairments in spatial cognitive function and the underlying mechanism is still unclear.

Methods

A transgenic APP/PS1 mouse model of AD amyloidosis was used in this study. Behavioral tests were conducted to observe the protective effects of A2AR blockade on early spatial memory deficits in 4-month old APP/PS1 mice. To investigate the underlying synaptic mechanism of the protective effects of A2AR blockade, we further examined long-term potentiation (LTP) and network excitation/inhibition balance of dentate gyrus (DG) region, which is relevant to unique synaptic functions of immature adult-born granule cells (abGCs). Subsequently, the protective effects of A2AR blockade on dendritic morphology and synaptic plasticity of 6-week-old abGCs was investigated using retrovirus infection and electrophysiological recordings. The molecular mechanisms underlying neuroprotective properties of A2AR blockade on the synaptic plasticity of abGCs were further explored using molecular biology methods.

Results

APP/PS1 mice displayed DG-dependent spatial memory deficits at an early stage. Additionally, impaired LTP and an imbalance in network excitation/inhibition were observed in the DG region of APP/PS1 mice, indicating synaptic structural and functional abnormalities of abGCs. A2AR was found to be upregulated in the hippocampus of the APP/PS1 mouse model of AD. Treatment with the selective A2AR antagonist SCH58261 for three weeks significantly ameliorated spatial memory deficits in APP/PS1 mice and markedly restored LTP and network excitation/inhibition balance in the DG region. Moreover, SCH58261 treatment restored dendritic morphology complexity and enhanced synaptic plasticity of abGCs in APP/PS1 mice. Furthermore, SCH58261 treatment alleviated the impairment of synaptic plasticity in abGCs. It achieved this by remodeling the subunit composition of NMDA receptors and increasing the proportion of NR2B receptors in abGCs of APP/PS1 mice.

Conclusions

Blockade of A2AR improves early spatial memory deficits in APP/PS1 mice, possibly by reversing synaptic defects of abGCs. This finding suggests that A2AR blockade could be a potential therapy for AD.
The remodeling of metabolic brain pattern in patients with extracranial diffuse large B-cell lymphoma
Authors: Liu Junyi , Tang Ming , Zhu Dongling , Ruan Ge , Zou Sijuan , Cheng Zhaoting , Zhu Xiaohua , Zhu Yuankai
Published: October 2023

Background

Owing to the advances in diagnosis and therapy, survival or remission rates for lymphoma have improved prominently. Apart from the lymphoma- and chemotherapy-related somatic symptom burden, increasing attention has been drawn to the health-related quality of life. The application of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has been routinely recommended for the staging and response assessment of FDG-avid lymphoma. However, up till now, only a few researches have investigated the brain metabolic impairments in patients with pre-treatment lymphoma. The determination of the lymphoma-related metabolic brain pattern would facilitate exploring the tailored therapeutic regimen to alleviate not only the physiological, but also the psychological symptoms. In this retrospective study, we aimed to establish the diffuse large B-cell lymphoma-related pattern (DLBCLRP) of metabolic brain network and investigate the correlations between DLBCLRP and several indexes of the staging and response assessment.

Results

The established DLBCLRP was characterized by the increased metabolic activity in bilateral cerebellum, brainstem, thalamus, striatum, hippocampus, amygdala, parahippocampal gyrus and right middle temporal gyrus and by the decreased metabolic activity in bilateral occipital lobe, parietal lobe, anterior cingulate gyrus, midcingulate cortex and medial frontal gyrus. Significant difference in the baseline expression of DLBCLRP was found among complete metabolic response (CMR), partial metabolic response (PMR) and progressive metabolic disease (PMD) groups (P < 0.01). DLBCLRP expressions were also significantly or tended to be positively correlated with international prognostic index (IPI) (rs = 0.306, P < 0.05), lg(total metabolic tumor volume, TMTV) (r = 0.298, P < 0.05) and lg(total lesion glycolysis, TLG) (r = 0.233, P = 0.064). Though no significant correlation of DLBCLRP expression was found with Ann Arbor staging or tumor SUVmax (P > 0.05), the post-treatment declines of DLBCLRP expression were significantly positively correlated with Ann Arbor staging (rs = 0.284, P < 0.05) and IPI (rs = 0.297, P < 0.05).

Conclusions

The proposed DLBCLRP would lay the foundation for further investigating the cerebral dysfunction related to DLBCL itself and/or treatments. Besides, the expression of DLBCLRP was associated with the tumor burden of lymphoma, implying a potential biomarker for prognosis.
Effects of novel androgen receptor signaling inhibitors on PSMA PET signal intensity in patients with castrate-resistant prostate cancer: a prospective exploratory serial imaging study
Authors: Sonni Ida , Gafita Andrei , Unterrainer Lena M. , Alano Rejah M. , Lira Stephanie , Shen John , Drakaki Alexandra , Grogan Tristan , Rettig Matthew B. , Czernin Johannes , Calais Jeremie
Published: October 2023

Background

PSMA expression is influenced by hormonal status. We evaluated changes in PSA and whole-body 68Ga-PSMA-11 PET/CT (WB-PSMA PET) after initiation of androgen receptor signaling inhibitors (ARSi).

Methods

Prospectively enrolled patients with metastatic castration-resistant prostate cancer (mCRPC) initiating ARSi underwent serial PSA measurements and WB-PSMA PET at baseline, 1-week, and 3-months post-ARSi. We correlated WB-PSMA PET metrics and PSA kinetics after ARSi to 1-year clinical outcome.

Results

Due to low enrollment rate, the study was closed before reaching the recruitment goal of 30 patients. Nine patients were enrolled. At 1-year, unfavorable outcome was documented in 6/9 (66%) patients. Nine/9 patients completed PSMA PET at 1-week, 5/9 at 3-months. Changes in PSA, PSMA-VOL, SUVmean and SUVmax were − 12%, + 5%, + 3%, and + 10% at 1-week, − 42%, − 16%, − 15% and − 17% at 3-months, respectively.

Conclusions

Our prospective trial involving 9 mCRPC patients initiating ARSi did not show significant modulation of PSMA expression measured on WB-PSMA PET at 1-week. This study was registered on clinicaltrials.gov (NCT04279561).
Mortality, incidence, and microbiological documentation of ventilated acquired pneumonia (VAP) in critically ill patients with COVID-19 or influenza
Authors: Laurichesse Guillaume , Schwebel Carole , Buetti Niccolò , Neuville Mathilde , Siami Shidasp , Cohen Yves , Laurent Virginie , Mourvillier Bruno , Reignier Jean , Goldgran‐Toledano Dany , Ruckly Stéphane , de Montmollin Etienne , Souweine Bertrand , Timsit Jean‐François , Dupuis Claire ,   for the OUTCOME R. E. A. network
Published: October 2023

Background

Data on ventilator associated pneumonia (VAP) in COVID-19 and influenza patients admitted to intensive care units (ICU) are scarce. This study aimed to estimate day-60 mortality related to VAP in ICU patients ventilated for at least 48 h, either for COVID-19 or for influenza, and to describe the epidemiological characteristics in each group of VAP.

Design

Multicentre retrospective observational study.

Setting

Eleven ICUs of the French OutcomeRea™ network.

Patients

Patients treated with invasive mechanical ventilation (IMV) for at least 48 h for either COVID-19 or for flu.

Results

Of the 585 patients included, 503 had COVID-19 and 82 had influenza between January 2008 and June 2021. A total of 232 patients, 209 (41.6%) with COVID-19 and 23 (28%) with influenza, developed 375 VAP episodes. Among the COVID-19 and flu patients, VAP incidences for the first VAP episode were, respectively, 99.2 and 56.4 per 1000 IMV days (p < 0.01), and incidences for all VAP episodes were 32.8 and 17.8 per 1000 IMV days (p < 0.01). Microorganisms of VAP were Gram-positive cocci in 29.6% and 23.5% of episodes of VAP (p < 0.01), respectively, including Staphylococcus aureus in 19.9% and 11.8% (p = 0.25), and Gram-negative bacilli in 84.2% and 79.4% (p = 0.47). In the overall cohort, VAP was associated with an increased risk of day-60 mortality (aHR = 1.77 [1.36; 2.30], p < 0.01), and COVID-19 had a higher mortality risk than influenza (aHR = 2.22 [CI 95%, 1.34; 3.66], p < 0.01). VAP was associated with increased day-60 mortality among COVID-19 patients (aHR = 1.75 [CI 95%, 1.32; 2.33], p < 0.01), but not among influenza patients (aHR = 1.75 [CI 95%, 0.48; 6.33], p = 0.35).

Conclusion

The incidence of VAP was higher in patients ventilated for at least 48 h for COVID-19 than for influenza. In both groups, Gram-negative bacilli were the most frequently detected microorganisms. In patients ventilated for either COVID-19 or influenza VAP and COVID-19 were associated with a higher risk of mortality.
Unraveling the South Asian enigma: concurrent manifestations of child anthropometric failures and their determinants in selected South Asian countries
Authors: Saif Sabeen , Anwar Sofia
Published: October 2023

Malnutrition among children is pervasive in South Asia and there are also reports of overnutrition. To better understand this phenomenon, we need a composite measure. However, the existing measures such as CIAF (Composite Index of Anthropometric Failure) and its revised version have ignored the overnutrition aspect of the phenomenon. This study proposes an extended version of CIAF which also considers overnutrition. This new measure was compared with the existing measures by using data from 1990 to 2018 for three selected South Asian countries including Pakistan, India and Bangladesh. We also examined the effects of socioeconomic and environmental variables on the outcome variable. The results reveal that the new measure (ECIAF) is better at measuring the phenomena. The burden of overall malnutrition has been decreased in the region. However, an increase in the concomitant prevalence of wasting and underweight is observed in both Pakistan and India and stunting and overweight is observed only in India. Besides, political stability, prevalence of undernourishment, anemia in children, mother’s education, household size, dependency ratio, air pollution and unimproved sanitation are significantly correlated with childhood malnutrition. The findings also testified to long-run cointegrating relationship among the variables.
Genoprotective potential of Macaranga species phytochemical compounds on HT-29 human colorectal adenocarcinoma cell line
Authors: Siew Ee Ling , Pearanpan Lishantini , Zamkhuri Zhafri , Nordin Fariza Juliana , Ooi Theng Choon , Chan Kok Meng , Kamarozaman Aisyah Salihah , Ahmat Norizan , Rajab Nor Fadilah
Published: October 2023

Background

The species of genus Macaranga are widely found in Malaysian secondary forests and has been used as an alternative for treating varieties of illness. Studies have shown that the medicinal properties of this genus contain anti-inflammatory, antioxidant, and anti-cancer effects. This study aimed to determine the cytotoxicity of six isolated phytochemicals from Macaranga heynei (M. heynei), Macaranga lowii and Shorea leprosula on HT-29 human colorectal adenocarcinoma cell lines.

Results

One out of six isolated phytochemical compounds, identified as “Laevifolin A”, showed a cytotoxicity with an IC50 value of 21.2 µM following 48 h treatment as detected using Sulforhodamine B (SRB) assay. Additionally, no induction of apoptosis and oxidative stress were observed on Laevifolin A treated HT-29 cells as determined using Annexin V-FITC/PI assay and dihydroethidine (HE) staining, respectively. Additionally, no damage to the DNA were observed as measured using the Alkaline Comet assay. Further investigation on menadione-induced oxidative DNA damage showed the genoprotective potential of Laevifolin A on HT-29 cells.

Conclusions

In conclusion, this study indicated that only one compound (Laevifolin A) that extracted from M. heynei has the cytotoxicity potential to be developed as an anticancer agent in human colorectal adenocarcinoma. However, besides exhibiting cytotoxic effect, the compound also exhibits genoprotective capability that warrant further investigation.
Breakfast patterns in relation to physical activity among school adolescents in Karachi, Pakistan
Authors: Ashfaq Mehak Muhammad , Jawed Nida , Safdar Nilofer Fatimi , Bhutto Adnan Ahmed
Published: October 2023

Background

Unhealthy habits and poor diet patterns are significant concerns among adolescents, impacting their overall quality of life. This study aimed to assess and improve these habits in adolescents.

Methods

This is a cross-sectional study conducted in 2017–2018 in Karachi. The research participants, aged 11–17 years, were drawn from lower-middle-income secondary schools using multistage random selection. Sociodemographics, the Physical Activity Questionnaire for Adolescents (PAQ-A), and breakfast consumption were determined through questionnaire and a food frequency survey.

Results

A study of 334 school-going adolescents in Karachi, Pakistan, found that 82% consumed breakfast daily, with chapatti being the preferred choice (72.2%). Physical activity levels varied, but 56.6% engaged in regular activity. No significant differences were found in breakfast consumption by age or parental education.

Conclusions

Understanding South Asian adolescents’ breakfast habits is crucial. Promoting healthier breakfast options and increased physical activity are recommended for long-term well-being, with further research needed for targeted interventions.
The effects of short video app-guided loving-kindness meditation on college students’ mindfulness, self-compassion, positive psychological capital, and suicide ideation
Authors: Liu Chao , Chen Hao , Zhang Ayuan , Gong XiaoGang , Wu Kan , Liu Chia-Yih , Chiou Wen-Ko
Published: October 2023

Objective

The study investigated the effects of a short video app guided loving-kindness meditation (LKM) on college students’ mindfulness, self-compassion, positive psychological capital, and suicide ideation. The purpose of the study is to investigate the intervention effect of LKM training on suicidal ideation among college students with the help of the short video application and to provide an empirical basis for the exploration of early suicide intervention strategies for college students.

Methods

We recruited 80 college students from a university in China. The final 74 eligible participants were divided into two groups: app use group (n = 37) and the control group (n = 37). The app group accepted an 8-week app use interference, while the control group underwent no interference. We measured four major variable factors (mindfulness, self-compassion, positive psychological capital, and suicide ideation) before and after the app use intervention.

Results

In the app group, self-compassion and positive psychological capital were significantly higher, and suicide ideation was significantly lower than the control group. In the control group, there were no noticeable differences in any of the four variables between the pre-test and post-test.

Conclusions

Our findings demonstrate that the short video app guided LKM may help to improve self-compassion, and positive psychological capital, and reduce suicide ideation. The finding of the short video app-guided LKM’s effect extends our understanding of the integrative effects of positive psychology and digital media on the reduction of suicide ideation.
Development and validation of the activities and participation children and adolescents –neck (APCAN) measure
Authors: Tiwari Devashish , Naidoo Keshrie , Eddy Emily Z. , Chatiwala Naseem , Kaur Maninderjit
Published: October 2023

Background

Neck pain is the fourth leading cause of years lost to disability in children warranting a comprehensive assessment of neck pain and its impact on activities and participation. Hence, the purpose of this study was to develop a new measure (i.e., Activities and Participation Children and Adolescents -neck [APCAN]) specific to evaluating activity limitation and participation restrictions in children and adolescents and to establish its content validity.

Methods

Development and content validation of the APCAN was completed in four steps: (1) item development, (2) item evaluation by content experts, (3) content validity calculation, and (4) cognitive testing via interviews to ensure readability and comprehension of the items on the APCAN.

Results

An initial pool of 52 items was created that was revised to 20 items after modified Delphi process and cognitive interviews. Each item was rated on a 0–10 numeric rating scale (0 = not difficult at all, 10 = extremely difficult) with higher scores indicating higher perceived disability secondary to neck pain. All 20 items retained the content validity ratio critical value and the overall content validity index was 0.88 indicating excellent content validity.

Conclusion

The APCAN provides an easy to use, comprehensive assessment of functional limitations associated with neck pain in children.
The Arabic Hospital Anxiety and Depression Scale: validation in a sample of Lebanese patients with cancer
Authors: Ibrahim Nour , Yamout Dahlia , Bizri Maya , Taher Ali
Published: October 2023

Background

Depression and anxiety are common comorbid psychological disorders among patients with cancer. Despite the wide use of the Arabic Hospital and Anxiety Scale (HADS) in oncological settings, it has not been yet validated among Lebanese patients with cancer. We aimed to assess the reliability and validity of the HADS in a sample of Lebanese patients with cancer. One-hundred one Lebanese patients diagnosed with cancer presenting to the Ambulatory Care Center in the Hematology Oncology Department at the American University of Beirut Medial Center filled the Arabic version of the HADS. The Generalized Anxiety Disorder 7-Item Scale (GAD-7) and the Patient Health Questionnaire 9-Item Scale (PHQ-9) were used to assess its concurrent validity in capturing anxiety and depression, respectively.

Results

Reliability analysis using Cronbach’s alpha (α) coefficient revealed good internal consistency for the Arabic HADS (α = 0.89) and both subscales (α = 0.86 for depression and α = 0.78 for anxiety). Correlations between HADS with both GAD-7 and PHQ-9 were statistically significant and strong for both depression (r = 0.795; p < 0.0001) and anxiety (r = 0.727; p < 0.0001). Confirmatory factor analysis revealed that the observed data fits the two-factor model of depression and anxiety (Kaiser–Meyer–Olkin = 0.86; Tucker Lewis Index = 0.879; root-mean-square error of approximation = 0.08). Depression and anxiety rates were approximately 52% and 25%, respectively.

Conclusion

We conclude that the Arabic version of the HADS is a credible and valid tool for clinical assessment of psychological distress (anxious and depressive states) among Lebanese patients with cancer.
Ameloblastic fibro-dentinoma: a rare mixed odontogenic tumor case report with review of literature
Authors: Darwish Nihal Mohamed Ahmed , Amer Hatem Wael Abdel-Fattah , Mahrous Nesma Nabil Mohamed
Published: October 2023

Background

Ameloblastic fibro-dentinoma is considered a rare, benign, mixed odontogenic tumor that occurs mainly in the posterior mandible in the 1st–2nd decade of life. Although the clinical behavior of Ameloblastic fibro-dentinoma is similar to that of ameloblastic fibroma, there is a debate about whether Ameloblastic fibro-dentinoma is a developing hamartomatous odontoma or a separate neoplastic odontogenic tumor like ameloblastic fibroma. However, it is important to understand the histopathogenesis of this rare tumor.

Case presentation

A case report presenting an 11-year-old male child with a swelling in the posterior mandible. Radiographic examination revealed a multilocular lesion with mixed radiodensity related to the impacted lower left second premolar tooth. Incisional biopsy was done, and microscopic examination revealed cords and nests of odontogenic follicles lined by ameloblast-like cells and central stellate reticulum-like cells in the primitive ecto-mesenchymal stroma with areas of dentinoid material and osteodentin. The diagnosis was ameloblastic fibro-dentinoma. Surgical excision of the lesion was done, and the patient was followed up for 1 year without evidence of recurrence.

Conclusion

Reporting such a rare entity clarifies the debate about its nature and the importance of early diagnosis of lesions that are associated with unerupted teeth showing how it is effective in early management and prognosis.
The ABA–AtNAP–SAG113 PP2C module regulates leaf senescence by dephoshorylating SAG114 SnRK3.25 in Arabidopsis
Authors: Wang Gaopeng , Liu Xingwang , Gan Su-Sheng
Published: October 2023

We previously reported that ABA inhibits stomatal closure through AtNAP-SAG113 PP2C regulatory module during leaf senescence. The mechanism by which this module exerts its function is unknown. Here we report the identification and functional analysis of SAG114, a direct target of the regulatory module. SAG114 encodes SnRK3.25. Both bimolecular fluorescence complementation (BiFC) and yeast two-hybrid assays show that SAG113 PP2C physically interacts with SAG114 SnRK3.25. Biochemically the SAG113 PP2C dephosphorylates SAG114 in vitro and in planta. RT-PCR and GUS reporter analyses show that SAG114 is specifically expressed in senescing leaves in Arabidopsis. Functionally, the SAG114 knockout mutant plants have a significantly bigger stomatal aperture and a much faster water loss rate in senescing leaves than those of wild type, and display a precocious senescence phenotype. The premature senescence phenotype of sag114 is epistatic to sag113 (that exhibits a remarkable delay in leaf senescence) because the sag113 sag114 double mutant plants show an early leaf senescence phenotype, similar to that of sag114. These results not only demonstrate that the ABA-AtNAP-SAG113 PP2C regulatory module controls leaf longevity by dephosphorylating SAG114 kinase, but also reveal the involvement of the SnRK3 family gene in stomatal movement and water loss during leaf senescence.

Graphical Abstract
Disclinations in vibration-induced size segregation
Authors: Amnuanpol S. , Kongkarat S.
Published: October 2023

Vibration segregates large disks embedded in a medium of small disks and transits structurally the arrays of disks from the loosely disordered packing to the densely ordered packing. Our experiments on a monodisperse or bidisperse medium of small disks reveal that several types of topological defects, emerging during this disordered-to-ordered transition, are an isolated 5-fold disclination, an isolated 7-fold disclination, a 5-7 pair, a quadrupole of two 5-7 pairs, a grain boundary of alternating 5- and 7-fold disclinations and a closed loop of a grain boundary. The dominant types are an isolated 5-fold disclination and a 5-7 pair. Vibration eliminates more effectively 5-7 pairs than isolated 5-fold disclinations. After sufficient vibration the resulting orientational order is quasi-long-range only in two cases, i) in a monodisperse medium and ii) in a dilute bidisperse medium vibrated at small acceleration, while translational order is always short-range. The arrangement of disks in such two cases is thus hexatic-like.
Molecular compartmentalization in a syncytium: restricted mobility of proteins within the sea urchin skeletogenic mesenchyme
Authors: Khor Jian Ming , Guerrero-Santoro Jennifer , Ettensohn Charles A.
Published: October 2023

Multinucleated cells, or syncytia, are found in diverse taxa. Their biological function is often associated with the compartmentalization of biochemical or cellular activities within the syncytium. How such compartments are generated and maintained is poorly understood. The sea urchin embryonic skeleton is secreted by a syncytium, and local patterns of skeletal growth are associated with distinct sub-domains of gene expression within the syncytium. For such molecular compartments to be maintained and to control local patterns of skeletal growth: (1) the mobility of TFs must be restricted to produce stable differences in the transcriptional states of nuclei within the syncytium; and (2) the mobility of biomineralization proteins must also be restricted to produce regional differences in skeletal growth. To test these predictions, we expressed fluorescently tagged forms of transcription factors and biomineralization proteins in sub-domains of the skeletogenic syncytium. We found that both classes of proteins have restricted mobility within the syncytium and identified motifs that limit their mobility. Our findings have general implications for understanding the functional and molecular compartmentalization of syncytia.
The Impact of Regulation on Innovation
Authors: Aghion Philippe , Bergeaud Antonin , Van Reenen John
Published: October 2023

We present a framework that can be used to assess the equilibrium impact of regulation on endogenous innovation with heterogeneous firms. We implement this model using French firm-level panel data, where there is a sharp increase in the burden of labor regulations on companies with 50 or more employees. Consistent with the model’s qualitative predictions, we find a fall in the fraction of innovating firms just to the left of the regulatory threshold. Furthermore, we find a reduction in the innovation response of firms to demand shocks just below the threshold. Regulation reduces aggregate innovation by 5.7 percent. (JEL D22, K31, L11, L25, L51, O31, O34)
Who Controls the Agenda Controls the Legislature
Authors: Ali S. Nageeb , Bernheim B. Douglas , Bloedel Alexander W. , Battilana Silvia Console
Published: October 2023

We model legislative decision-making with an agenda setter who can propose policies sequentially, tailoring each proposal to the status quo that prevails after prior votes. Voters are sophisticated, and the agenda setter cannot commit to future proposals. Nevertheless, the agenda setter obtains her favorite outcome in every equilibrium regardless of the initial default policy. Central to our results is a new condition on preferences, manipulability, that holds in rich policy spaces, including spatial settings and distribution problems. Our findings therefore establish that, despite the sophistication of voters and the absence of commitment power, the agenda setter is effectively a dictator. (JEL D71, D72, D78)
Motifs in SARS-CoV-2 evolution
Authors: Barrett Christopher , Bura Andrei C. , He Qijun , Huang Fenix W. , Li Thomas J.X. , Reidys Christian M.
Published: October 2023

We present a novel framework enhancing the prediction of whether novel lineage poses the threat of eventually dominating the viral population. The framework is based purely on genomic sequence data, without requiring prior established biological analysis. Its building blocks are sets of coevolving sites in the alignment (motifs), identified via coevolutionary signals. The collection of such motifs forms a relational structure over the polymorphic sites. Motifs are constructed using distances quantifying the coevolutionary coupling of pairs and manifest as coevolving clusters of sites. We present an approach to genomic surveillance based on this notion of relational structure. Our system will issue an alert regarding a lineage, based on its contribution to drastic changes in the relational structure. We then conduct a comprehensive retrospective analysis of the COVID-19 pandemic based on SARS-CoV-2 genomic sequence data in GISAID from October 2020 to September 2022, across 21 lineages and 27 countries with weekly resolution. We investigate the performance of this surveillance system in terms of its accuracy, timeliness, and robustness. Lastly, we study how well each lineage is classified by such a system.
Development of a SNaPshot assay for the genotyping of organellar SNPs in four closely related pines
Authors: Szczepański Sebastian , Łabiszak Bartosz , Wachowiak Witold
Published: October 2023

Mitochondrial (mtDNA) and chloroplast (cpDNA) polymorphisms are valuable resources to study past demographic changes, phylogenetics and evolution, especially in forest tree species, where these genomes are haploid and uniparentally transferred. The organellar markers were usually scored separately using direct sequencing or PCR-based approaches, which can be time-consuming and expensive, especially in large-scale population genetics research. In this study, we developed an efficient and cost-effective SNaPshot assay for genotyping preselected ­mtDNA and cpDNA polymorphism in four closely related pine species including Scots pine (Pinus sylvestris L.) and three taxa from the Pinus mugo complex. We validated the method by genotyping the samples derived from 12 populations of the species from their wide geographical distribution range in Europe. The results proved high accuracy of the method with a genotyping success rate of 99.7%. The set of assayed markers shows significant genetic variation. By using multiplex SNaPshot assay, we provided an efficient and sensitive molecular tool for intra- and interspecific genetic analyses. The presented protocol is useful for fast and relatively cheap SNP genotyping of organelle genome of closely related pine species. The assayed SNPs allow studying the species discrimination and detailed investigations of their population history and structure. Given its numerous benefits and efficient genotyping rate, the SNaPshot method appears to be a valuable and practical resource for studying the genetic makeup of forest tree species. Particularly, it proves to be advantageous for population genetics.
Lab-on-chip (LoC) application for quality sperm selection: An undelivered promise?
Authors: Shukla Shiva K , Gaudriault Pierre , Corbera Antoni
Published: October 2023

Quality sperm selection is essential to ensure the effectiveness of assisted reproductive techniques (ART). However, the methods employed for sperm selection in ART often yield suboptimal outcomes, contributing to lower success rates. In recent years, microfluidic devices have emerged as a promising avenue for investigating the natural swimming behavior of spermatozoa and developing innovative approaches for quality sperm selection. Despite their potential, the commercial translation of microfluidic-based technologies has remained limited. This comprehensive review aims to critically evaluate the inherent potential of lab-on-chip technology in unraveling sophisticated mechanisms encompassing rheotaxis, thermotaxis, and chemotaxis. By reviewing the current state-of-the-art associated with microfluidic engineering and the swimming of spermatozoa, the goal is to shed light on the multifaceted factors that have impeded the broader commercialization of these cutting-edge technologies and recommend a commercial that can surmount the prevailing constraints. Furthermore, this scholarly exploration seeks to enlighten and actively engage reproductive clinicians in the profound potential and implications of microfluidic methodologies within the context of human infertility.