bluuebunny/crossref_metadata_2025 huggingface dataset:
The Guantánamo Artwork and Testimony of Moath al-Alwi: Deaf Walls Speak, edited by Alexandra S. Moore and Elizabeth Swanson
Authors: Spear Charlotte
Published: October 2024

This review considers The Guantánamo Artwork and Testimony of Moath Al-Alwi: Deaf Walls Speak, edited by Alexandra S. Moore and Elizabeth Swanson, and explores the book’s key implications for human rights practitioners and their organizations.
Insect parasitoids of fall armyworm (Lepidoptera: Noctuidae) in Africa and Asia and their adoption in integrated pest management of maize in Nepal
Authors: Muniappan Rangaswamy , Sah Lalit Prasad , Nyaupane Sushil , Bhandari Ghanashyam , Tiwari Sundar , Bajracharya Ajaya Shree Ratna , Gupta Ankita , Subaharan Kesavan
Published: October 2024

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) is native to the neotropics and invaded Africa and Asia in 2016 and 2018, respectively, and Nepal in 2019. Even though it is a polyphagous pest, the population that reached Africa and Asia prefers maize. As native parasitoids and predators form the first line of defense against new invaders, a study conducted in Nepal identified 9 species of parasitoids, namely, 2 eggs, 1 egg-larval, 4 larval, 1 larval-pupal, and 1 pupal parasitoid of FAW. A comparison was made on the list of parasitoids and predators of FAW recorded in other countries in Asia and Africa. The Feed the Future Nepal Integrated Pest Management Lab, was involved in human and institutional capacity building for survey, collection, identification, and multiplication of parasitoids of FAW. A national augmentative biological control program has been developed and included as a component of the IPM package for maize in Nepal.
Evaluation of a risk-sharing agreement for atezolizumab treatment in patients with non-small cell lung cancer: a strategy to improve access in low-income countries
Authors: Arrieta Oscar , Ramos-Ramírez Maritza , Garcés-Flores Homero , Cabrera-Miranda Luis A , Gómez-García Ana Pamela , Soto-Molina Herman , Cardona Andrés F , Valencia-Velarde Ángel , Gálvez-Niño Marco , Guzmán-Vázquez Silvia
Published: October 2024

Background

Using immune checkpoint inhibitors (IO) is a promising approach to maximize clinical benefits for patients with non-small cell lung cancer (NSCLC). PD-L1 expression serves as a predictive factor for treatment outcomes with IO. However, the high cost of this treatment creates significant barriers to access. Substantial evidence demonstrates the sustained clinical benefits experienced by patients who respond to immunotherapy. While IOs show promise in NSCLC treatment, their high cost poses access barriers.

Aim

This study focused on a prospective cost analysis conducted at a high-specialty health facility to assess the economic implications of implementing a risk-sharing agreement (RSA) for atezolizumab in NSCLC.

Methods

The study included 30 patients with advanced NSCLC, with the pharmaceutical company funding the initial cycles. If patients responded, a government program covered costs until disease progression.

Results

A median progression-free survival of 4.67 months across populations, rising to 9.4 months for responders. The 2-year overall survival rate for the response group was 64%, significantly higher than for non-response. Without an RSA, a total treatment cost of $881 859.36 ($29 395.31/patient) was reported, compared to $530 467.12 ($17 682.24/patient) with an RSA, representing a 40% cost reduction. In responders, the average cost per year of life per patient dropped by 22%. Risk-sharing, assessed through non-parametric tests, showed a statistically significant difference in pharmacological costs (P < .001).

Conclusion

Implementing RSAs can optimize resource allocation, making IO treatment more accessible, especially in low-income countries.
Energy efficient robot operations by adaptive control schemes
Authors: Choi Minje , Park Seongjin , Lee Ryujeong , Kim Sion , Kwak Juhyeon , Lee Seungjae
Published: October 2024

Energy efficiency is key to achieving the Sustainable Development Goals globally. Energy consumption in the transport sector is constantly increasing, and governments are implementing policies to reduce car use by shifting the focus from roads to walking. With the rise of pedestrianization policies, autonomous mobile robots (AMRs) are becoming increasingly useful. Autonomous robotic services are being used in various fields such as traffic management, logistics, and personal mobility assistance. However, AMRs research has focused on technology development, route planning, and cost reduction, with relatively little research on how to make robots more energy efficient. As these autonomous robotic services become more popular, there is a need to discuss how to efficiently use energy. This study analyses the characteristics of the hardware required for AMRs to operate. In particular, the density of obstacles in the surrounding environment is defined as saturation for the use of Lidar, and the effectiveness of the proximal policy optimization reinforcement learning algorithm is analysed to propose an energy efficiency plan for the saturation density. In the future, a large number of robots are expected to be used, and efficient energy use of such hardware will contribute to building sustainable cities.
“I can’t tell you what freedom is ’cause I’ve never seen it”: Addressing the Omission of Liberation Narratives in Sociology
Authors: Allen Shaonta’ E
Published: October 2024

While liberation, or the process of freeing marginalized individuals and groups from societal oppression and domination, is referenced across many sub-disciplines of sociology, it surprisingly remains under-conceptualized in sociological literature. To address this omission, the present study responds to the following query: how, if at all, do Black individuals conceive of a Black liberated future? I draw on data from 65 in-depth interviews with Black Millennials during Black Lives Matter to capture their imaginings of a Black liberated future. Findings reveal that participants construct four types of liberation narratives when detailing their perceptions of Black freedom: 1) Liberation via Reformation, 2) Liberation via Reconstruction, 3) Liberation via Afrocentrism, and 4) Liberation as Inconceivable. I ultimately argue that liberation narratives function as resistant knowledge projects and, as such, are significant socio-political artifacts and resources for future generations of change agents, community organizers, and social movements actors. Altogether, this study demonstrates how rectifying the omission of liberation narratives magnifies our sociological knowledge about marginalized groups and deepens our analytic capacity to make sense of their ontological approaches toward politics of liberation and imaginings of their collective futures.
Taking Control of Your Functional Cognitive Symptoms Workbook: A Novel Intervention
Authors: Cotton E. , Mordecai K. L. , McWhirter L. , Cabreira V. , Van Patten R. , Silverberg N.D. , Kaat A.J. , LaFrance W.C.
Published: October 2024

Background

Functional cognitive disorder (FCD) is a subtype of functional neurological disorder (FND). FCD can present with various cognitive symptoms, precipitants, and comorbidities (other FNDs, concussion, fatigue, fibromyalgia, etc.). However, there are no widely available existing behavioral health interventions for FCD. The authors’ aim was to develop a therapist-guided treatment for FCD for widespread use among civilians and Veterans.

Methods

We adapted a well-known, evidence-based treatment for functional seizures (an adjacent condition often with cognitive symptoms), to fit the hypothesized mechanisms of FCD. The process is presented in GUIDED format (GUIDance for the rEporting of intervention Development). Key processes included determining broad intervention framework, detailed FCD specific content based on expert consensus, evidence, theory, target population centered approaches, specialty subgroup consideration and target population stakeholder feedback for Veteran and civilian populations.

Findings

We have created a comprehensive 14-chapter, manualized, therapist-guided neurobehavioral therapy protocol to target FCD symptoms independent of etiology – theTaking Control of Your Functional Cognitive Symptoms Workbook. Initial feasibility, tolerability, and utility were completed with 2 target population stakeholders with FCD (one civilian, one Veteran; both PGI-C rating = 1 “Very Much Improved”). The Template for Intervention Description and Replication (TIDieR) checklist is provided as a supplemental table.

Interpretation

This new promising multi-modality behavioral health intervention can be considered Stage 1 (i.e. intervention generation, refinement, modification, adaptation, and pilot testing). Further pilot testing is being conducted and will need to be followed by traditional efficacy testing (Stage 2).

Key Messages

FCD is an increasingly recognized subtype of FND. Despite existing models of FCD mechanisms, there are no widely available dedicated FCD-symptom focused behavioral health interventions.

We have created theTaking Control of Your Functional Cognitive Symptoms: Workbook, a 14-chapter manualized therapist-guided neurobehavioral therapy protocol to target FCD symptoms regardless of cause / associated conditions, which shows early feasibility and promising clinical utility.
Study Research Protocol for Phenome India-CSIR Health Cohort Knowledgebase (PI-CHeCK): A Prospective multi-modal follow-up study on a nationwide employee cohort
Authors:   Phenome India Consortium, Sengupta Shantanu
Published: October 2024

Predicting individual health trajectories based on risk scores can help formulate effective preventive strategies for diseases and their complications. Currently, most risk prediction algorithms rely on epidemiological data from the Caucasian population, which often do not translate well to the Indian population due to ethnic diversity, differing dietary and lifestyle habits, and unique risk profiles. In this multi-center prospective longitudinal study conducted across India, we aim to address these challenges by developing clinically relevant risk prediction scores for cardio-metabolic diseases specifically tailored to the Indian population. India, which accounts for nearly 18% of the global population, also has a significant diaspora worldwide. This program targets longitudinal collection and bio-banking of samples from over 10,000 employees both working and retirees of the Council of Scientific and Industrial Research and their spouses, with baseline sample collection already completed. During the baseline collection, we gathered multi-parametric data including clinical questionnaires, lifestyle and dietary habits, anthropometric parameters, lung function assessments, liver elastography by Fibroscan, electrocardiogram readings, biochemical data, and molecular assays, including but not limited to genomics, plasma proteomics, metabolomics, and fecal microbiome analysis. In addition to exploring associations between these parameters and their cardio-metabolic outcomes, we plan to employ artificial intelligence algorithms to develop predictive models for phenotypic conditions. This study could pave the way for precision medicine tailored to the Indian population, particularly for the middle-income strata, and help refine the normative values for health and disease indicators in India.
Bio-medical Big Data Operating System (Bio-OS): An Integrated Data Mining Environment for Data Intensive Scientific Research
Authors: Liu Ji-Long , Yang Li-Guang , Xiao Qing-Yu , Li Zhao-Qiang , Cheng Jin-Yu , Chen Zi-Ru , Zhou Jian-Wen , Wan Xiang , Chang Tsung-Hui , Zhang Xin , Li Yi-Xue
Published: October 2024

The advent of high throughput sequencing has ushered life science and clinical research into the era of big data, posing significant challenges for reproducibility due to the complexity of data integration and analysis. Although the FAIR principles advocate for the transparent and reliable sharing of scientific data, their implementation remains hampered by technical barriers. The Global Alliance for Genomics and Health (GA4GH) has made strides in standardizing data and tools, yet a comprehensive solution for reproducibility is lacking. In response, we present BioOS, an open source, cloud native Biomedical big data Operating System. This system encapsulates study components data, code, tools, and environments into workspaces, enhancing reproducibility and validation. BioOS employs JSON Schema for machine readability and includes a Hierarchy Hash Mechanism to ensure data integrity. Adhering to GA4GH protocols, BioOS simplifies complex technological implementations, making advanced research tools accessible. Demonstrated through representative workspaces, BioOS fosters seamless research replication, peer review, and editorial evaluation. Its cloud native infrastructure supports dynamic resource allocation, enabling efficient handling of large scale analyses. By integrating AI driven Large Language Models, BioOS enhances user interaction and operational flexibility. As an evolving open source platform, BioOS exemplifies a transformative approach to biomedical research, aligning with FAIR principles and advancing the AI for Science paradigm, thus promoting a more connected, efficient, and impactful research environment.
Template-driven dynamic functional network connectivity predicts medication response for major depression and bipolar disorders
Authors: Baker Bradley T. , Osuch Elizabeth , Langenecker Scott , Fournier Jay , Turner Jessica , Youngstrom Eric , Calhoun Vince D.
Published: October 2024

The process of finding reliable treatment for major depression and bipolar disorder can be arduous. The myriad behavioral symptoms presented by patients and resistance to treatment from particular medication classes complicate standard diagnostic and prescription methodologies, often requiring multiple attempted treatments during which symptoms may still be present. Physiological information such as neuroimaging scans may help to alleviate some of the uncertainty surrounding diagnosis and treatment when incorporated into a clinical setting. Changes in functional magnetic resonance imaging show particular promise, as the incorporation of dynamical information may provide insights into physiological changes prior to static, structural changes. In this work, we present a novel method for generating robust and replicable dynamic functional network connectivity (dFNC) features from neuroimaging data using a template of dynamic states derived from a large, non-affected data set. We demonstrate that this template-driven dFNC approach expands on standard dFNC approaches by allowing for the derivation of a continuous state-contribution time series. We demonstrate that the derived biomarkers can support high predictive performance for the identification of medication class and non-responders while also expanding the set of biomarkers available for studying differences in mood disorder medication response.
Computational analysis of optogenetic inhibition of CA1 neurons using a data-efficient and interpretable potassium and chloride conducting opsin model
Authors: Weyn Laila , Tarnaud Thomas , Schoeters Ruben , De Becker Xavier , Joseph Wout , Raedt Robrecht , Tanghe Emmeric
Published: October 2024

Optogenetic inhibition of excitatory populations has been suggested as a novel technique for the treatment of refractory epilepsy. While this approach holds significant potential, achieving seizure suppression in animal models using optogenetics has proven challenging. This difficulty can be attributed to a suboptimal stimulation method that involves numerous complex variables. To provide insight into these parameters, the behavior of the chloride conducting opsin, GtACR2, was fitted to a mathematical description and combined with a conductance-based model of a pyramidal CA1 neuron. The resulting model was adapted to add the ability to study potassium conducting opsins and used to demonstrate that the effect of an optogenetic modulation setup is highly dependent on its parameters and the physiological conditions of the neuronal environment. Stronger inhibition is observed at higher pulse repetition frequencies and duty cycles. Furthermore, potassium conducting opsins were shown to be more stable in use than chloride conducting ones. The dependence of these observations on the opsin model fit was found to be negligible. To determine this, a simplified model (22OMs) is proposed that permits easy implementation of the experimentally derived parameters describing the opsin’s opening and closing dynamics into its mathematical description. This model was also employed to determine that the impact of varying the opsin’s dynamics is insignificant when the opening and closing time constants are altered by a factor between 0.5 and 2. Consequently, this study provides insights into the stimulation and physiological parameters influencing the outcome of an optogenetic inhibition approach and offers a new tool that will facilitate future research into the development of an improved optogenetic modulation protocol for seizure suppression.
Darwin’s Naturalization Conundrum explained by gradients of environmental stress and disturbance
Authors: Galmán Andrea , Alexander Jake M. , Cavieres Lohengrin A. , Daehler Curtis C. , Seipel Tim , Winter Marten , Andersen Kelly M , Lembrechts Jonas J. , Aschero Valeria , Arévalo Sierra José Ramón , Barros Agustina , Buhaly Meike , Backes Amanda Ratier , Dar Pervaiz A. , Fuentes-Lillo Eduardo , Jiménez Alejandra , Küffer Christoph , Larson Christian D. , Mihoc Maritza , Milbau Ann , Morgan John W. , McDougall Keith , Müllerová Jana , Naylor Bridgett , Nuñez Martin A. , Padrón Mederos Miguel Antonio , Pauchard Aníbal , Rew Lisa J. , Reshi Zafar A. , Sandoya Veronica , Shah Manzoor A , Shannon James M. , Walsh Neville , Valencia Graciela , Vorstenbosch Tom , Wright Genevieve , Zong Shengwei , Haider Sylvia
Published: October 2024

Darwin’s Naturalization Conundrum (DNC) states that non-native species closely related to the native community are either more likely to succeed because shared adaptations help them overcome environmental filtering, or less likely to succeed because of strong competition with their native relatives. Despite extensive research, no general patterns have so far emerged. One reason may be that the relative importance of competition and environmental filtering depends on environmental conditions. To test this hypothesis, we conducted a global assessment of DNC examining patterns of phylogenetic relatedness of non-native plant species to the native community along gradients of elevation and anthropogenic disturbance in mountains. Phylogenetic distance of non-native to native species decreased with increasing elevation and in disturbed plant communities. Our results help resolve DNC by showing that the environmental context sets expectations for patterns of relatedness between non-native and native species and helps illuminate the ecological and evolutionary processes generating these patterns.
Benzamidine-Mediated Inhibition of Human Lysozyme Aggregation: Differential Ligand Binding in Homologous Proteins
Authors: Hima Sree , Remya Chandran , Abhithaj J , Arun K.G. , Sabu A. , Vasudevan D. M. , Dileep K.V.
Published: October 2024

Amyloid fibril formation is a hallmark of several protein misfolding diseases, including systemic hereditary amyloidosis (SHA), in which lysozyme aggregates into plaques, causing inflammation in various tissues. SHA is a rare disease with no current drug treatment options. In our efforts to identify potential therapeutics for SHA, we investigated the inhibitory effects of benzamidine (BEN) on the fibrillation of human lysozyme (HL). Multiple biophysical assays demonstrated BEN’s ability to effectively prevent amyloid formation. Intrinsic fluorescence measurements highlighted BEN’s interaction with HL. We inferred the binding mode of BEN to HL through ITC experiments, molecular docking, and molecular dynamics simulations, confirmed BEN’s binding at the active site, particularly near stretch-2 (residues 52-64), a key region in its anti-amyloidogenic activity. This interaction differed from the previously reported interaction with HEWL. Further, microscopy analyses, including scanning electron microscopy (SEM) and transmission electron microscopy (TEM), further supported these findings by showing reduced fibril formation and alterations in fibril morphology in the presence of BEN. Importantly, BEN exhibited no cytotoxic effects in HEK-293 cells, reinforcing its potential as a therapeutic candidate for amyloidosis. These results provide strong evidence of BEN’s anti-amyloidogenic activity and offer a foundation for future drug development targeting lysozyme amyloidosis.
Integrating target capture with whole genome sequencing of recent and natural history collections to explain the phylogeography of wild-growing and cultivatedCannabis
Authors: Balant Manica , Vitales Daniel , Wang Zhiqiang , Barina Zoltán , Fu Lin , Gao Tiangang , Garnatje Teresa , Gras Airy , Hayat Muhammad Q. , Oganesian Marine , Pellicer Jaume , Salami Alireza S. , Seregin Alexey P. , Stepanyan-Gandilyan Nina , Sultana Nusrat , Tsooj Shagdar , Urgamal Magsar , Vallès Joan , van Velzen Robin , Pokorny Lisa
Published: October 2024

Cannabishas provided important and versatile services to humans for millennia. Domestication and subsequent dispersal have resulted in various landraces and cultivars. Unravelling the phylogeography of this genus poses considerable challenges due to its complex history.

We relied on a Hyb-Seq approach (combining target capture with shotgun sequencing), with the universal Angiosperms353 enrichment panel, to explore the genetic structure of wild-growing accessions and cultivars by implementing phylogenomic and population genomic workflows on the same Hyb-Seq data.

Our findings support the treatment ofCannabisas a monotypic genus (C. sativaL.), structured into three main genetic groups—E Asia, Paleotropis, and Boreal—with clear phylogeographic signal despite significant levels of admixture. The E Asia group was sister to the Paleotropis and the Boreal groups. Individuals within the Paleotropis group could be further structured into three subgroups: Iranian Plateau, C & S China and Himalayas, and Indoafrica. Individuals from the Boreal group split into two subgroups: Eurosiberia and W Mongolia and Caucasus and Mediterranean. Hemp and drug-type landraces and cultivars consistently matched their putative geographic origin.

These findings enhance our understanding of the genetic patterns inCannabisand provide a framework for future research into its current and past genetic diversity.
Evaluating the Biocontrol Potential of Pythium oligandrum and Serratia proteamaculans in Controlling Phytophthora plurivora in European beech (Fagus sylvatica)
Authors: Kelbessa Bekele Gelena , Samuelsson Anton , Ghadamgahi Farideh , Witzell Johanna , Whisson Stephen C. , Ortiz Rodomiro , Grenville-Briggs Laura J. , Vetukuri Ramesh R.
Published: October 2024

In recent years, the plant pathogenPhytophthora plurivorahas caused severe damage to beech forests in many European countries, including Sweden. In many affected areas, few protective measures are in place due to fears about potential negative impacts on the ecosystem or public health. The research presented in this article assesses the biocontrol potential of the oomycetePythium oligandrumand the bacteriumSerratia proteamaculansagainstP. plurivora, with experiments performed under bothin vitroand greenhouse conditions, which could represent a step forward in developing a safe treatment for European beech forests. Thein vitroresults revealed thatP. oligandrumandS. proteamaculanssignificantly inhibited pathogen growth and stimulated a shift in the hyphal growth pattern towards shorter, branched hyphae with many hyphal swellings and thickened cell walls. The experiments conducted in greenhouses showed that treating three-month-old beech seedlings withP. oligandrumandS. proteamaculanscounteracts theP. plurivorapathogen and reduces disease symptoms on the aerial and underground parts of the plant. GC-MS analysis detected the volatile organic compounds alpha-pinene, 2,5-dimethyl-pyrazine, and 3-methyl-1-butanol fromS. proteamaculans;these compounds have the potential to inhibit pathogen growth. The disease suppression demonstrated by these biocontrol agents could thus be related to the synergistic effect of competition for nutrients with the secretion of hydrolytic enzymes and VOCs; moreover, induced systemic resistance may be triggered under greenhouse conditions. In conclusion, usingP. oligandrumandS. proteamaculanscould represent an environmentally friendly strategy for effectively controlling the disease caused byP. plurivorain beech.
In silicogeneration of synthetic cancer genomes using generative AI
Authors: Díaz-Navarro Ander , Zhang Xindi , Jiao Wei , Wang Bo , Stein Lincoln
Published: October 2024

Cancer originates from alterations in the genome, and understanding how these changes lead to disease is crucial for achieving the goals of precision oncology. Connecting genomic alterations to health outcomes requires extensive computational analysis using accurate algorithms. Over the years, these algorithms have become increasingly sophisticated, but a severe shortage of open access gold-standard datasets presents a fundamental challenge. Since genomic data is considered personal health information, only an extremely limited number of deeply sequenced legacy cancer genomes can be shared and redistributed. As a result, tool benchmarking is often conducted on the same small set of genomes sequenced with older technologies and uncertain ground truths. This is a major obstacle to the development of improved analytic tools.

To address this issue, we have developed OncoGAN, a novel generative AI tool that uses a combination of generative adversarial networks and tabular variational autoencoders to generate realistic but entirely synthetic cancer genomes based on training sets derived from large-scale genomic projects. Our results demonstrate that this approach accurately reproduces the scale, distribution, and characteristics of somatic point mutations, copy number alterations and structural variants across multiple common cancer types, while protecting donors’ privacy information. OncoGAN accurately recapitulates tumor type-specific mutational signatures as well as the positional distribution of somatic mutations. To evaluate the fidelity of the simulations, we tested the synthetic genomes using DeepTumour, a software capable of identifying tumor types based on mutational patterns, and demonstrated a high level of concordance between the synthetic genome tumor type and DeepTumour’s prediction of the type. We also showed that augmenting real donor data with OncoGAN-generated synthetic data could be used to train a more accurate version of DeepTumour.

This tool will allow the generation of an extensive and realistic set of training and testing cancer genomes whose ground truth is known exactly. This advance provides computational biologists with the ability to develop realistic cancer genome benchmarking sets and make them available to the research community for the testing, development and enhancement of cancer genome analysis tools.
PFKFB3 protein in adipose tissue contributes to whole body glucose homeostasis
Authors: Griesel Beth A. , Olson Ann Louise
Published: October 2024

Age-dependent changes in adipose tissue are thought to play a role in development of insulin resistance. A major age-dependent change in adipose tissue is the downregulation of key proteins involved in carbohydrate metabolism. In the current study, we investigate the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) a key governor of the rate of glycolysis in adipocytes via the synthesis of fructose-2,6-bisphosphate that was significantly down-regulated in aged mice. We employed an adipocyte-specific PFKFB3 mouse line to investigate the role of PFKFB3 on adipocyte function. In both aged mice and PFKFB3-knockout mice, we observed an increase in O-glcNAcylated proteins consistent with a shift in glucose metabolism toward the hexosamine biosynthetic pathway. Under chow-fed conditions, PFKFB3 knockout resulted in significantly smaller adipocyte area, but no difference in total fat mass. While glucose tolerance was unchanged under chow conditions, when mice were challenged with a 4 wk high fat feeding, PFKFB3 deletion led to a greater decrease in glucose tolerance as well as a significant increase in macrophage infiltration. These results indicate that perturbation of the glycolytic pathway in adipose tissue has multiple effects of adipocyte biology and may play a significant role in metabolic changes associated with aging. Results of this student support the notion that changes in glucose metabolism in adipose tissue impact whole body metabolism.
Efficacy of Acupuncture on Lower Limb Motor Dysfunction Following Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Chen Peng , Jin Xing , Yu Debiao , Chen Xiaotin , Lin Yaoyu , Wu Fuchun , Shao Bin
Published: October 2024

Background

Acupuncture is widely used for Lower Limb Motor Dysfunction Following Stroke (LLMD) in China but its effect is unclear. We aim to evaluate the effect of acupuncture for LLMD.

Methods

We searched eight databases, including PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, VIP, and CBM, up to December 2023. Randomized controlled trials on acupuncture therapy for LLMD after stroke were enrolled in this study. Outcome measures comprised motor function, balance function, walking ability, and daily living activities. Two researchers conducted independent literature screening, data extraction, and quality assessment in accordance with Cochrane Collaboration network’s standards. Review Manager 5.3 and Stata 17.0 were used in data analysis. Results were presented as mean difference (MD) or standardized mean difference (SMD) with 95% confidence interval (95% CI).

Results

Twelve studies involving 1318 patients, most of which showed low or unclear risk of bias, were included in this review. Meta-analysis results indicate that compared with conventional treatment, acupuncture intervention can improve scores in Fugl–Meyer Assessment for lower scale (SMD=0.41, 95% CI (−0.92, –0.04), Z=2.16, P =.03), Berg Balance Scale (SMD=-0.86, 95%CI (−1.65, –0.07), Z=2.14, P=.03), Functional Ambulation Category scale (SMD=-0.74, 95%CI (−2.33, 0.84), Z=0.92, P=.36), and Modified Barthel Index Scale (SMD=0.27, 95%CI (−0.30, 0.84), Z=0.94, P=.35).

Conclusion

The results of this study suggest that acupuncture combined rehabilitation training may be more effective than pure treatment in improving LLMD, balance function, walking ability, and daily living activities after stroke. Despite limitations due to the low quality of the included studies and methodological constraints, acupuncture combined rehabilitation training may serve as an effective approach for the treatment of LLMD poststroke.
The association between medical accessibility and glycemic status in patients with type 2 diabetes mellitus: A retrospective study in Taiwan rural population
Authors: Sun Chong-Fong , Pan Bo-Lin , Wang Pei-Ming , Huang Kun-Siang , Lu Yueh-Chien , Kung Hsin-Yi , Chiang Jui-Chin
Published: October 2024

Introduction

Type 2 diabetes mellitus represents a significant chronic health concern, with rural populations being particularly vulnerable due to geographic and socio-economic barriers to healthcare access. To date, few studies have focused on the medical accessibility of rural diabetic patients in Taiwan. This study aims to explore the association between the proximity to healthcare facilities and glycohemoglobin levels in the rural Taiwanese population.

Methods

We conducted a retrospective cross-sectional study in rural districts of southern Taiwan. Medical accessibility was calculated from subject’s address to medical units by Google Maps platform. Spearman’s Rank Analysis was performed for the correlation between distance from patient’s address to medical units and glycohemoglobin level. Logistic regression was applied to identify factors associated with glycemic control.

Results

In total, 117 patients with type 2 diabetes mellitus were enrolled (mean glycohemoglobin: 8.17±1.92%). Glycohemoglobin level was modestly and positively associated with distance to clinic (Rho: 0.252) and hospital (Rho: 0.241) respectively. In logistic regression analysis, good glycemic control (glycohemoglobin less than 7%) was associated with covariates as not-working status, the address district near downtown, fasting plasma glucose equal to or less than 130 mg/dL, and normal high-density lipoprotein cholesterol level.

Conclusion

Our study reveals that accessibility to healthcare facility is modestly correlated with long-term glycemic status in Taiwan rural diabetic population. Besides, we also identified several protective factors associated with chronic glycemic status. These findings may pave the way for improvement of policy and healthcare strategies in rural diabetic care.
MRI signature of brain age underlying post- traumatic stress disorder in World Trade Center responders
Authors: Invernizzi Azzurra , La Rosa Francesco , Sather Anna , Rechtman Elza , Jalees Maryam , Nabeel Ismail , Pellecchia Alison C. , Santiago-Michels Stephanie , Bromet Evelyn J. , Lucchini Roberto G. , Luft Benjamin J. , Clouston Sean A. , Beck Erin S , Tang Cheuk Y. , Horton Megan K.
Published: October 2024

The men and women involved in rescue and recovery operations at the 9/11 World Trade Center (WTC) site have a greater prevalence (23%) of persistent, clinically significant post- traumatic stress disorder (PTSD). Recent structural and functional magnetic resonance imaging (MRI) studies demonstrate significant neural differences between WTC responders with and without PTSD. Here, we used brain age, a novel MRI-based data-driven biomarker optimized to detect accelerated structural aging, and examined the impact of PTSD on this process. Using BrainAgeNeXt, a novel convolutional neural network trained and validated on 11,574 magnetic resonance imaging (MRI) T1- weighted scans, we predicted brain age in WTC responders with PTSD (WTC-PTSD,n= 47) and age/sex matched responders without PTSD (non-PTSD,n= 52). Predicted Age Difference (PAD) was then calculated for each WTC responder by subtracting chronological age from brain age. A positive PAD indicates that the responder’s brain is aging faster than expected for their chronological age. We found that PAD is significantly greater with WTC-PTSD compared to non-PTSD responders (p< 0.001). Further, we found that WTC exposure duration (months working on site) moderates the association between PTSD and PAD (p=0.0050). Our results suggested that brain age is a valid biomarker to compare aging trajectories in responders with and without PTSD. In particular, PTSD may be a substantial risk factor for accelerated neurodegeneration in this vulnerable and aging population.
Highly adaptive LASSO: Machine learning that provides valid nonparametric inference in realistic models
Authors: Butzin-Dozier Zachary , Qiu Sky , Hubbard Alan E. , Shi Junming (Seraphina) , van der Laan Mark J.
Published: October 2024

Abstract

Understanding treatment effects on health-related outcomes using real-world data requires defining a causal parameter and imposing relevant identification assumptions to translate it into a statistical estimand. Semiparametric methods, like the targeted maximum likelihood estimator (TMLE), have been developed to construct asymptotically linear estimators of these parameters. To further establish the asymptotic efficiency of these estimators, two conditions must be met: 1) the relevant components of the data likelihood must fall within a Donsker class, and 2) the estimates of nuisance parameters must converge to their true values at a rate faster thann−1/4. The Highly Adaptive LASSO (HAL) satisfies these criteria by acting as an empirical risk minimizer within a class ofcàdlàgfunctions with a bounded sectional variation norm, which is known to be Donsker. HAL achieves the desired rate of convergence, thereby guaranteeing the estimators’ asymptotic efficiency. The function class over which HAL minimizes its risk is flexible enough to capture realistic functions while maintaining the conditions for establishing efficiency. Additionally, HAL enables robust inference for non-pathwise differentiable parameters, such as the conditional average treatment effect (CATE) and causal dose-response curve, which are important in precision health. While these parameters are often considered in machine learning literature, these applications typically lack proper statistical inference. HAL addresses this gap by providing reliable statistical uncertainty quantification that is essential for informed decision-making in health research.
Circulating cardiovascular proteomic associations with genetics and disease
Authors: McGurk Kathryn A. , Curran Lara , Sau Arunashis , Ng Fu Siong , Halliday Brian , Ware James S. , O’Regan Declan P.
Published: October 2024

Background

The analysis of the circulating proteome can identify translational modifiers and biomarkers of disease expressivity and severity at a given time point. Here we explore the relationships between protein measures implicated in cardiovascular disease and whether they mediate causal relationships between cardiovascular risk factors and disease development.

Methods

To understand the relationships between circulating biomarkers and genetic variants, medications, anthropometric traits, lifestyle factors, imaging-derived measures, and diagnoses of cardiovascular disease, we analysed measures of nine plasma proteins witha prioriroles in genetic and structural cardiovascular disease or treatment pathways (ACE2, ACTA2, ACTN4, BAG3, BNP, CDKN1A, NOTCH1, NT-proBNP, and TNNI3) from the Pharma Proteomics Project of the UK Biobank cohort (over 45,000 participants sampled at recruitment).

Results

We identified significant variability in circulating proteins with age, sex, ancestry, alcohol intake, smoking, and medication intake. Phenome-wide association studies highlighted the range of cardiovascular clinical features with relationships to protein levels. Genome-wide genetic association studies identified variants nearGCKR,APOE, andSERPINA1, that modified multiple circulating protein levels (BAG3, CDKN1A, and/or NOTCH1). NT-proBNP and BNP levels associated with variants inBAG3. ACE2 levels were increased with a diagnosis of hypertension or diabetes and were influenced by variants in genes associated with diabetes (HNF1A, HNF4A). Two-sample Mendelian randomisation identified ACE2 as protective for systolic blood pressure and Type-2 diabetes.

Conclusions

From a panel of circulating proteins, the results from this observational study provide evidence that ACE2 is causally associated with hypertension and diabetes. This suggests that ACE2 stimulation may provide additional protection from these cardiovascular diseases. This study provides an improved understanding of the circulating pathways depicting cardiovascular disease dynamics.

Graphical abstract
Global comparative structural analysis of responses to protein phosphorylation
Authors: Correa Marrero Miguel , Mello Victor Hugo , Sartori Pablo , Beltrao Pedro
Published: October 2024

Post-translational modifications (PTMs), particularly protein phosphorylation, are key regulators of cellular processes, impacting numerous aspects of protein activity. Despite widespread phosphorylation of eukaryotic proteomes, the function of most phosphosites remains unknown. Elucidating the structural mechanisms underlying phosphorylation is crucial for understanding its regulatory roles. Here, we conducted a comparative structural analysis of phosphorylated and non-phosphorylated proteins taken from the Protein Data Bank (PDB). Our study systematically evaluates how phosphorylation affects backbone conformation, protein dynamics, and mechanical strain. We found that phosphorylation commonly induces small, stabilizing conformational changes through conformational selection and frequently modulates local residue fluctuations, influencing overall protein motion. Notably, a small but significant subset of phosphosites shows mechanical coupling with functional sites, aligning with the domino model of allosteric signal transduction. This work provides a foundation for studying phosphorylation and other PTMs in their structural context, which will guide the rational design of synthetic phosphosites and enable the engineering of PTM-driven regulatory circuits in synthetic biology.
Measurement and classification of bold-shy behaviours in medaka fish
Authors: Pierotti Saul , Brettell Ian , Fitzgerald Tomas , Herder Cathrin , Aadepu Narendar , Pylatiuk Christian , Wittbrodt Joachim , Birney Ewan , Loosli Felix
Published: October 2024

Motivation

Boldness-shyness is considered a fundamental axis of behavioural variation in humans and other species, with obvious adaptive causes and evolutionary implications. Besides an individual’s own genetics, this phenotype is also affected by the genetic makeup of peers in the individual’s social environment. To identify genetic determinants of variation along the bold-shy behavioural axis, a reliable experimental and analytical setup able to highlight direct and indirect genetic effects is needed.

Results

We describe a custom assay designed to detect bold-shy behaviours in medaka fish, combining an open-field and novel-object component. We use this assay to explore direct and social genetic effects on the behaviours of 307 pairs of fish from five inbred medaka strains. Applying a Hidden Markov Model (HMM) to classify behavioural modes, we find that direct genetic effects influence the proportions of time the five strains spent in slow-moving states, explaining up to 29.7% of the variance in time spent in those states. We also found that an individual’s behaviour is influenced by the genetics of its tank partner, explaining up to 8.64% of the variance in the time spent in slow-moving states. Our behavioural assay in combination with the HMM analysis is applicable to follow-up genetic linkage studies of genetic variants involved in direct behavioural effects and indirect social genetic effects. A suitable genetic resource for such studies, the Medaka Inbred Kiyosu-Karlsruhe panel (MIKK) has recently been established.
Phosphorylation-dependent tuning of mRNA deadenylation rates
Authors: Stowell James A.W. , Yu Conny W.H. , Chen Zhuo A. , Lee Giselle , Morgan Tomos , Sinn Ludwig , Agnello Sylvie , O’Reilly Francis J. , Rappsilber Juri , Freund Stefan M.V. , Passmore Lori A.
Published: October 2024

mRNA decay is a major determinant of gene regulation that is controlled through shortening of mRNA poly(A) tails by the Ccr4-Not complex. The specificity of deadenylation can be mediated through RNA adaptors – RNA-binding proteins that tether substrate mRNAs to Ccr4-Not in a regulated and context-specific manner. Interaction with Ccr4-Not is mediated by intrinsically disordered regions (IDRs) within the RNA adaptors. Due to the difficulty in studying large IDR-containing complexes, the determinants of specificity and their regulation remain unclear. Here we use structural biology and biochemical reconstitution to show that dispersed segments within IDRs of RNA adaptors bind to several distinct binding sites on Ccr4-Not through multivalent interactions. We further demonstrate that binding can be modulated by phosphorylation, altering the consequent deadenylation rate in a continuously tunable manner. This mechanism is broadly applicable in evolutionarily divergent IDRs from multiple RNA adaptors including fission yeast Puf3, and human Pumilio/PUM1 and Tristetraprolin/TTP. Together, our work suggests that multivalent interactions and phosphorylation represent conserved strategies for regulating gene expression. Thus, in response to cellular cues, mRNA decay can be regulated by a graded mechanism, rather than a bistable on/off switch, rationalizing how post-transcriptional gene expression is fine-tuned.
In vitrobiofilms ofClostridioides difficileundomesticated strains: Morphology and properties according to strain diversity
Authors: Lemaire Anaïs , Bridoux Ludovic , Costache Vlad , Crouzols Aline , Barbut Frédéric , Petry Sandrine , Poquet Isabelle
Published: October 2024

Clostridioides difficileis a Gram-positive, spore-forming, obligate anaerobe and an entero-pathogen representing a One Health problem.C. difficileinfections are difficult to treat and recurrences frequent.C. difficilebiofilms may play a role in persistence. We studied the biofilms formedin vitroby a collection ofC. difficileundomesticated strains (n=27, 20 toxigenic and 7 non-toxigenic) of 11 PCR-ribotypes (WRT) and isolated from equids. After growth in rich BHIS medium supplemented with glucose for 48h, the biomass of biofilms stained by crystal violet, i. e. adhesive to the surface, was measured, while intact biofilms were observedin situ, by confocal laser scanning microscopy, to determine their total biovolume and 3D morphology. All biofilms were relatively similar, even though adhesive, stained biofilms of non-toxigenic strains of ribotype 009 significantly displayed highest biomass. These results suggested that strains of ribotype 009 were able to form a highly cohesive and polystyrene-adhesive biofilm than any other strains. 8 common, representative ribotypes in equids, including 6 clinically important ribotypes in humans, were then selected and one strain chosen for each of them. Their biofilms and planktonic cultures grown under the same conditions were compared for sporulation, toxin production and susceptibility to vancomycin at a highly inhibitory concentration (8 MIC). In both the biofilm and planktonic culture of all selected strains, sporulation was low and toxin production undetectable. The addition of vancomycin at T0=24h followed by a 24 hours exposure barely reduced the viability of neither planktonic cultures nor biofilms of any strains. On the contrary, for all selected strains, addition of vancomycin at T0=6h followed by a 24 hours exposure significantly and more efficiently reduced the viability of planktonic cultures than that of biofilms, which was not decreased at all in the case of strains of ribotype WRT 005, 009 and 035. The biofilms of these selected strains of eight ribotypes, compared to their planktonic cultures, therefore showed a higher tolerance to vancomycin, suggesting that they could play a role in persistence.
Establishment & Characterization of a Non-Adherent Insect Cell Line for Cultivated Meat
Authors: Letcher Sophia M. , Calkins Olivia P. , Clausi Halla J. , McCreary Aidan , Trimmer Barry A. , Kaplan David L.
Published: October 2024

This study presents a blueprint for developing, scaling, and analyzing novel insect cell lines for food. The large-scale production of cultivated meat requires the development and analysis of cell lines that are simple to grow and easy to scale. Insect cells may be a favorable cell source due to their robust growth properties, adaptability to different culture conditions, and resiliency in culture. Cells were isolated from Tobacco hornworm (Manduca sexta)embryos and subsequently adapted to single-cell suspension culture in animal-free growth media. Cells were able to reach relatively high cell densities of over 20 million cells per mL in shake flasks. Cell growth data is presented in various culture vessels and spent media analysis was performed to better understand cell metabolic processes. Finally, a preliminary nutritional profile consisting of proximate, amino acid, mineral, and fatty acid analysis is reported.

Graphical Abstract