bluuebunny/crossref_metadata_2025 huggingface dataset:
Navigating polycrisis: long-run socio-cultural factors shape response to changing climate
Authors: Hoyer Daniel , Bennett James S. , Reddish Jenny , Holder Samantha , Howard Robert , Benam Majid , Levine Jill , Ludlow Francis , Feinman Gary , Turchin Peter
Published: September 2023

Climate variability and natural hazards like floods and earthquakes can act as environmental shocks or socioecological stressors leading to instability and suffering throughout human history. Yet, societies experience a wide range of outcomes when facing such challenges: some suffer from social unrest, civil violence or complete collapse; others prove more resilient and maintain key social functions. We currently lack a clear, generally agreed-upon conceptual framework and evidentiary base to explore what causes these divergent outcomes. Here, we discuss efforts to develop such a framework through the Crisis Database (CrisisDB) programme. We illustrate that the impact of environmental stressors is mediated through extant cultural, political and economic structures that evolve over extended timescales (decades to centuries). These structures can generate high resilience to major shocks, facilitate positive adaptation, or, alternatively, undermine collective action and lead to unrest, violence and even societal collapse. By exposing the ways that different societies have reacted to crises over their lifetime, this framework can help identify the factors and complex social–ecological interactions that either bolster or undermine resilience to contemporary climate shocks.

This article is part of the theme issue ‘Climate change adaptation needs a science of culture’.
Climate change and long-term human behaviour in the Neotropics: an archaeological view from the Global South
Authors: Scheinsohn Vivian , Muñoz A. Sebastián , Mondini Mariana
Published: September 2023

In this paper, we argue for the inclusion of archaeology in discussions about how humans have contributed to and dealt with climate change, especially in the long term. We suggest Niche Construction Theory as a suitable framework to that end. In order to take into account both human and environmental variability, we also advocate for a situated perspective that includes the Global South as a source of knowledge production, and the Neotropics as a relevant case study to consider. To illustrate this, we review the mid-Holocene Hypsithermal period in the southern Puna and continental Patagonia, both in southern South America, by assessing the challenges posed by this climate period and the archaeological signatures of the time from a Niche Construction Theory perspective. Finally, we emphasize the importance of these considerations for policymaking.

This article is part of the theme issue ‘Climate change adaptation needs a science of culture’.
Associations between maternal pre-pregnancy BMI and infant striatal mean diffusivity
Authors: Rosberg Aylin , Merisaari Harri , Lewis John D. , Hashempour Niloofar , Lukkarinen Minna , Rasmussen Jerod M. , Scheinin Noora M. , Karlsson Linnea , Karlsson Hasse , Tuulari Jetro J.
Published: September 2023

Background/Objectives

It is well-established that parental obesity is a strong risk factor for associates with offspring obesity. Further, a converging body of evidence now suggests that maternal weight profiles may affect the developing offspring brain in a manner that confers future obesity risk. Here, we investigated how pre-pregnancy maternal weight status influences the reward-related striatal areas of the offspring brain duringin uterodevelopment.

Methods

We used diffusion tensor imaging to quantify the microstructure of the striatal brain regions of interest in neonates (N = 116 mean gestational weeks at birth 39.88, SD = 1.14; and at scan 43.56, SD = 1.05). Linear regression was used to test the associations between maternal pre-pregnancy body mass index and infant striatal mean diffusivity.

Results

A strong positive association was found between the maternal pre-pregnancy body mass index and newborn left caudate nucleus mean diffusivity. Results remained unchanged after the adjustment for covariates.

Conclusions

In uteroexposure to maternal adiposity might have a growth impairing impact on the mean diffusivity of infant left caudate nucleus. Considering the involvement of caudate nucleus in regulating eating behaviour and food-related reward processing later in life, this finding calls for further investigations to define the prognostic relevance of early life caudate development and weight trajectories of the offspring.
Identification and Establishing Floral calendar in, Jimma zone of Oromia Ethiopia
Authors: Bareke Tura , Roba Kasim , Addi Admassu
Published: September 2023

Honeybee colony performance as well as production of honey and other hive products depends on bee forages. The study was designed with objective to identify and establish flowering Calendar of bee plants for multiple honey production. Bee forage inventory was made in a plot size of 20mx20, for woody plants and 2mx2m for herbaceous bee forages. Based on the inventory of bee forages, pollen load collection and honey pollen analysis, 103 plant species were identified as source of nectar and pollen for honeybees. From identified plant species Ageratumconizoides, Guizotia scabra, Cordia africana, Datura arborea, Plantago lanceolatum, Rumex nervosus, andJusticia schimperina, were the major honey source plants in the area.The fresh weight of pollen collected at different months of the year indicated that significant amount of pollen was collected during September, October to November but decline of incoming pollen weight was recorded during, March and July. The major honey flow period of the area occurred during November and extends early December and late February. The minor honey flow also resulted May-June. The pollen analysis of honey samples revealed that three monofloral honey types were identified which include Guizotia,Vernonia and Croton monofloral honey types comprising the pollen frequency ranging from 45% to 100%. The study concluded that floral calendar of bee forages strictly dependent on the seasonal availability of food sources and beekeepers should get awareness on management of honeybee colonies with the flowering calendar in the area to increase frequency of honey production.
Heteroscedastic Personalized Regression Unveils Genetic Basis of Alzheimer’s Disease Stratified by Cognitive Level
Authors: Chen Zhirong , Wang Haohan
Published: September 2023

In contemporary medical research, patient heterogeneity plays a pivotal role in comprehending intricate diseases such as Alzheimer’s disease and various forms of cancer. Specifically, in the genomic analysis of Alzheimer’s disease, individual patients may exhibit unique causal mutations that significantly influence their therapeutic trajectory. Conventional models that share numerous parameters across all individuals struggle to discern this heterogeneity and identify the influential factors for individuals. To tackle this challenge, we propose an innovative approach called Heteroscedastic Personalized Regression (Het-PR) to estimate the heterogeneity across samples and obtain personalized models for each sample. We demonstrate the effectiveness and robustness of Het-PR through both simulation and real data experiments. In the simulation experiment, we show that Het-PR outperforms other state-of-the-art models in capturing inter-sample heterogeneity. In the real data experiment, we apply Het-PR to Alzheimer’s data and show that it can identify persuasive selected genetic factors for each individual patient. Interestingly, our results suggest that there might be different associative SNPs for AD patients stratified by different cognitive levels.

Author summary

In medical research, it has been observed that causes of a disease vary significantly among individuals, especially when looking at complex diseases like Alzheimer’s disease and cancer. For Alzheimer’s disease, obesity, age, gender, and depression may play different roles across different patients. When studying the genes of Alzheimer’s patients, we find that each person might have their own unique genetic changes that can affect their treatment. For example, Alzheimer’s patients with different genetic mutations may respond differently to the same treatment. Traditional research methods often miss these individual differences and can’t always pinpoint important personalized factors for each patient, because they usually use one model for all patients. To better understand these differences, we’ve introduced a new method, Heteroscedastic Personalized Regression (Het-PR), which generates a personalized model for each individual. Our experiments show that Het-PR is more effective than other leading methods in identifying these patient differences and recognizing Alzheimer’s genetic basis for each patient through both simulation and real data experiments. When we used Het-PR on real Alzheimer’s data, it helped us spot key genetic factors for each patient. Additionally, in our study, we excitedly find that different genetic markers in Alzheimer’s patients are possibly based on their cognitive abilities. Software for Heteroscedastic Personalized Regression is available inhttps://github.com/rong-hash/Het-PR.
PERFECT: Personalized Exercise Recommendation Framework and architECTure
Authors: Mehrabadi Milad Asgari , Khatibi Elahe , Jimah Tamara , Labbaf Sina , Borg Holly , Pimentel Pamela , Dutt Nikil , Guo Yuqing , Rahmani Amir M.
Published: September 2023

Background

There are indisputable health benefits to physical activity (PA). By collecting and displaying individual exercise behaviors via wearable trackers, the Internet of Things (IoT) and mobile health (mHealth) have made it possible to correlate users’ physiological data and daily activity information with their fitness requirements.

Objective

This study aimed to recommend personalized exercise to non-pregnant subjects to increase their physical activity level.

Methods

We developed smartphone and smartwatch applications to collect, monitor, and recommend exercises using a contextual multi-arm bandit framework. Twenty female college students were recruited to test this mHealth exercise program.

Results

Our findings indicated an increase in daily exercise duration (P< .001), with average satisfaction scores for the walking and recommendation system components of 4.31 (0.60) and 3.69 (0.95), respectively, on a scale of 1 to 5. In addition, participants’ confidence in their capacity to complete the suggested walking exercises safely and the study’s ability to satisfy their needs for physical activity both received average scores of over 4.

Conclusions

A new era of mHealth systems has been ushered in by developments in the Internet of Things and wearable devices. Personalization of physical activity recommendations using such wearables has the potential to improve user engagement and performance. In this paper, we presented an exercise recommendation system based on reinforcement learning that uses biomarkers and the user’s context to recommend a unique walking exercise that enhances the user’s aerobic capacity.
Sequentially activated death complexes regulate pyroptosis and IL-1β release in response toYersiniablockade of immune signaling
Authors: Wertman Ronit Schwartz , Go Christina K. , Saller Benedikt S. , Groß Olaf , Scott Phillip , Brodsky Igor E.
Published: September 2023

TheYersiniavirulence factor YopJ potently inhibits immune signaling in macrophages by blocking activation of the signaling kinases TAK1 and IKK. In response, macrophages trigger a backup pathway of host defense that mediates cell death via the apoptotic enzyme caspase-8 and pyroptotic enzyme caspase-1. While caspase-1 is normally activated within multiprotein inflammasome complexes that contain the adaptor ASC and NLRs, which act as sensors of pathogen virulence, caspase-1 activation followingYersiniablockade of TAK1/IKK surprisingly requires caspase-8 and is independent of all known inflammasome components. Here, we report that caspase-1 activation by caspase-8 requires both caspase-8 catalytic and auto-processing activity. Intriguingly, while caspase-8 serves as an essential initiator of caspase-1 activation, caspase-1 amplifies its own activation through a feed-forward loop involving auto-processing, caspase-1-dependent cleavage of the pore-forming protein GSDMD, and subsequent activation of the canonical NLRP3 inflammasome. Notably, while caspase-1 activation and cell death are independent of inflammasomes duringYersiniainfection, IL-1β release requires the canonical NLPR3 inflammasome. Critically, activation of caspase-8 and activation of the canonical inflammasome are kinetically and spatially separable events, as rapid capase-8 activation occurs within multiple foci throughout the cell, followed by delayed subsequent assembly of a single canonical inflammasome. Importantly, caspase-8 auto-processing normally serves to prevent RIPK3/MLKL-mediated necroptosis, and in caspase-8’s absence, MLKL triggers NLPR3 inflammasome activation and IL-1β release. Altogether, our findings reveal that functionally interconnected but temporally and spatially distinct death complexes differentially mediate pyroptosis and IL-1β release to ensure robust host defense against pathogen blockade of TAK1 and IKK.

One Sentence Summary

Yersinia-induced cell death and IL-1β release are driven by spatially and temporally distinct but functionally connected death complexes.
Critical contribution of mitochondria in the development of cardiomyopathy linked to desmin mutation
Authors: Hovhannisyan Yeranuhi , Li Zhenlin , Callon Domitille , Suspène Rodolphe , Batoumeni Vivien , Canette Alexis , Blanc Jocelyne , Hocini Hakim , Lefebvre Cécile , El-Jahrani Nora , L’honoré Aurore , Kordeli Ekaterini , Fornes Paul , Concordet Jean-Paul , Tachdjian Gérard , Rodriguez Anne-Marie , Vartanian Jean-Pierre , Béhin Anthony , Wahbi Karim , Joanne Pierre , Agbulut Onnik
Published: September 2023

Beyond the observed alterations in cellular structure and mitochondria, the cellular mechanisms linking genetic mutations to the development of heart failure in patients affected by desmin defects remain unclear due, in part, to the lack of relevant human cardiomyocyte models. We investigated the role of mitochondria using cardiomyocytes derived from human induced pluripotent stem cells carrying the heterozygousDESE439Kdesmin mutation, that were either isolated from a patient or generated by gene editing. To increase physiological relevance, cells were either cultured on an anisotropic surface to obtain elongated and aligned cardiomyocytes, or as spheroids to create a micro- tissue. When applicable, results were confirmed with heart biopsies from the family harboringDESE439Kmutation. We show that mutant cardiomyocytes reproduce critical defects in mitochondrial architecture, respiratory capacity and metabolic activity as observed in patient’s heart tissue. To challenge the pathological mechanism, normal mitochondria were transferred inside the mutant cardiomyocytes. This treatment restored mitochondrial and contractile functions. This work demonstrates the crucial role of mitochondrial abnormalities in the pathophysiology of desmin-related cardiomyopathy, and opens-up new potential therapeutic perspectives.
Protein-Folding Chaperones Predict Structure-Function Relationships and Cancer Risk inBRCA1Mutation Carriers
Authors: Gracia Brant , Montes Patricia , Gutierrez Angelica Maria , Arun Banu , Karras Georgios Ioannis
Published: September 2023

Identifying pathogenic mutations and predicting their impact on protein structure, function and phenotype remain major challenges in genome sciences. Protein-folding chaperones participate in structure-function relationships by facilitating the folding of protein variants encoded by mutant genes. Here, we utilize a high-throughput protein-protein interaction assay to test HSP70 and HSP90 chaperone interactions as predictors of pathogenicity for variants in the tumor suppressor BRCA1. Chaperones bind 77% of pathogenic BRCA1-BRCT variants, most of which engaged HSP70 more than HSP90. Remarkably, the magnitude of chaperone binding to variants is proportional to the degree of structural and phenotypic defect induced byBRCA1mutation. Quantitative chaperone interactions identified BRCA1-BRCT separation-of-function variants and hypomorphic alleles missed by pathogenicity prediction algorithms. Furthermore, increased chaperone binding signified greater cancer risk in humanBRCA1carriers. Altogether, our study showcases the utility of chaperones as quantitative cellular biosensors of variant folding and phenotypic severity.

HIGHLIGHTS

Chaperones detect an abundance of pathogenic folding variants of BRCA1-BRCT.

Degree of chaperone binding reflects severity of structural and phenotypic defect.

Chaperones identify separation-of-function and hypomorphic variants.

Chaperone interactions indicate penetrance and expressivity ofBRCA1alleles.
Sensory Adaptations: Insights into the Vomeronasal System of the Iberian Wolf
Authors: Ortiz-Leal Irene , Torres Mateo V. , Barreiro-Vázquez José-Daniel , López-Beceiro Ana , Fidalgo Luis , Sanchez-Quinteiro Pablo
Published: September 2023

Wolves, like other canids, extensively use chemical signals for various aspects of communication, including territory maintenance, reproductive synchronization, and social hierarchy signaling. Pheromone-mediated chemical communication operates unconsciously among individuals, acting as a mysterious sixth sense that regulates both their physiology and behavior. Despite their crucial role in the life of the wolf, there is a surprising lack of comprehensive research on the neuroanatomical and physiological bases of chemical communication in wolves.

This study delves into the Iberian wolf vomeronasal system (VNS) and examines potential changes brought about by dog domestication. Our findings show that the Iberian wolf possesses a fully functional VNS vital for pheromone-mediated communication. While macroscopic similarities between the wolf and domestic dog VNS are observed, there are notable microscopic differences. These include the presence of neuronal clusters associated with the sensory epithelium of the vomeronasal organ (VNO) and a higher differentiation degree of the accessory olfactory bulb (AOB). Immunohistochemical markers reveal the expression of the two main families of vomeronasal receptors (V1R and V2R) in the VNO. However, only the V1R family is expressed in the AOB.

These findings not only provide deep insights into the VNS of the wolf but also hint at how domestication might have altered neural configurations that underpin species-specific behaviors. This understanding has implications for innovative strategies, such as employing semiochemicals for wolf population management, aligning with modern conservation goals.
Dendriticatoh1a+cells serve as transient intermediates during zebrafish Merkel cell development and regeneration
Authors: Craig Evan W. , Black Erik C. , Goo Camille E.A. , Swearer Avery Angell , Yee Nathaniel G. , Rasmussen Jeffrey P.
Published: September 2023

Sensory cells often adopt specific morphologies that aid in the detection of external stimuli. Merkel cells encode gentle touch stimuli in vertebrate skin and adopt a reproducible shape characterized by spiky, actin-rich microvilli that emanate from the cell surface. The mechanism by which Merkel cells acquire this stereotyped morphology from basal keratinocyte progenitors is unknown. Here, we establish that dendritic Merkel cells (dMCs) expressatonal homolog 1a (atoh1a), extend dynamic filopodial processes, and arise in transient waves during zebrafish skin development and regeneration. We find that dMCs share molecular similarities with both basal keratinocytes and Merkel cells, yet display mesenchymal-like behaviors, including local cell motility and proliferation within the epidermis. Furthermore, dMCs can directly adopt the mature, microvilliated Merkel cell morphology through substantial remodeling of the actin cytoskeleton. Loss of Ectodysplasin A signaling alters the morphology of dMCs and Merkel cells within specific skin regions. Our results show that dMCs represent an intermediate state in the Merkel cell maturation program and identify Ectodysplasin A signaling as a key regulator of Merkel cell morphology.
ULK1-dependent phosphorylation of PKM2 antagonizes O-GlcNAcylation and inhibits the Warburg effect in breast cancer
Authors: Zhou Zibin , Zheng Xiyuan , Zhao Jianxin , Yuan Aiyun , Shao Guangcan , Peng Bin , Dong Meng-Qiu , Xu Quan , Xu Xingzhi , Li Jing
Published: September 2023

Pyruvate kinase M2 (PKM2) is a central metabolic enzyme driving the Warburg effect in tumor growth. Previous investigations have demonstrated that PKM2 is subject to O-linked β-N-acetylglucosamine (O-GlcNAc) modification, which is a nutrient-sensitive post-translational modification. Here we found that unc-51 like autophagy activating kinase 1 (ULK1), a glucose-sensitive kinase, interacts with PKM2 and phosphorylates PKM2 at Ser333. Ser333 phosphorylation antagonizes PKM2 O-GlcNAcylation, promotes its tetramer formation and enzymatic activity, and decreases its nuclear localization. By downregulating glucose consumption and lactate production, PKM2 pS333 attenuates the Warburg effect. Through mouse xenograft assays, we demonstrate that the phospho-deficient PKM2-S333A mutant promotes tumor growthin vivo.In conclusion, we identified a ULK1-PKM2-c-Myc axis in inhibiting breast cancer, and a glucose-sensitive phosphorylation of PKM2 in modulating the Warburg effect.
Characterization of Novel Human β-glucocerebrosidase Antibodies for Parkinson Disease Research
Authors: Jong Tiffany , Gehrlein Alexandra , Sidransky Ellen , Jagasia Ravi , Chen Yu
Published: September 2023

BACKGROUND

Mutations inGBA1, which encodes the lysosome enzyme β-glucocerebrosidase (also referred to as acid β-glucosidase or GCase), are the most common genetic risk factor for Parkinson disease (PD) and dementia with Lewy bodies (DLB). Evidence also suggests that loss of GCase activity is implicated in PD withoutGBA1mutations. Consequently, therapies targeting GCase are actively being pursued as potential strategies to modify the progression of PD and related synucleinopathies. Despite this significant interest in GCase as a therapeutic target, the lack of well-characterized GCase antibodies continues to impede progress in the development of GCase-targeted therapies.

OBJECTIVE

This study aims to independently evaluate human GCase (hGCase) antibodies to provide recommendations for western blot, immunofluorescence, immunoprecipitation, and AlphaLISA (Amplified Luminescent Proximity Homogeneous Assay) assays.

METHODS

Two mouse monoclonal antibodies, hGCase-1/17 and hGCase-1/23, were raised against hGCase using imiglucerase, the recombinant enzyme used to treat patients, as the antigen. These novel antibodies, alongside commonly used antibodies in the field, underwent evaluation in a variety of assays.

RESULTS

The characterization of hGCase-1/17 and hGCase-1/23 using genetic models includingGBA1loss-of-function human neuroglioma H4 line and neurons differentiated from human embryonic stem cells (hESCs) revealed their remarkable specificity and potency in immunofluorescence and immunoprecipitation assays. Furthermore, a hGCase AlphaLISA assay with excellent sensitivity, a broad dynamic range, and suitability for high throughput applications was developed using hGCase-1/17 and hGCase-1/23, which enabled a sandwich assay configuration.

CONCLUSIONS

The hGCase immunofluorescence, immunoprecipitation, and AlphaLISA assays utilizing hGCase-1/17 and hGCase-1/23 will not only facilitate improved investigations of hGCase biology, but can also serve as tools to assess the distribution and effectiveness of GCase-targeted therapies for PD and related synucleinopathies.
Protocol and rationale for the International PANS Registry (IPR; pediatric acute onset neuropsychiatric syndrome)
Authors: Masterson Erin E. , Gavin Jessica M.
Published: September 2023

The International PANS Registry (IPR) is the first centralized, epidemiologic database of children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and PANS-like features and their siblings. PANS is a relatively new umbrella syndrome that lacks diagnostic biomarkers and is characterized by a set of working criteria. The failure to find a diagnostic biomarker is likely due to underpowered studies and inherent biological heterogeneity within PANS. Until the IPR was established, a critical barrier to large-scale longitudinal studies had been the absence of a large-scale epidemiologic study and a centralized database of children with PANS and PANS-like features. The IPR was created to serve as a translational health tool to accelerate research on the broad spectrum of complex pediatric neuroimmune conditions with the long-term goal of enabling a paradigm shift in this field from symptom-based evaluation and treatment towards biology-based diagnoses, treatments, screening, and surveillance. To date, the IPR has registered 1,666 families (3,247 children) and is the largest database in the world that gathers in-depth information on children with PANS and PANS-like features and their siblings. Enrollment in the IPR is open and ongoing; longitudinal follow up is planned. Participating families enroll their children with PANS and PANS-like features and their healthy siblings in the IPR via an online survey platform. The selection criteria for IPR enrollment are intentionally less restrictive than the current working criteria for PANS to generate a large recruitment pool and enable study of the broad spectrum of PANS-like conditions. The IPR is designed to enable ancillary study recruitment based on detailed selection criteria and to grow and expand in scope in the future. The IPR team is committed to data sharing and invites collaborators who will leverage existing data from the IPR database and extend knowledge in an area beyond the original scope of the IPR.
Status of Soil-Transmitted Helminthiasis Among Adolescents in Anaocha Local Government Area, Anambra State, Nigeria: Prevalence, Associated Factors, and Future Directions After a Decade of Ongoing Mass Administration of Medicines
Authors: Aribodor Ogechukwu B. , Jacob Eunice C. , Azugo Nwadiuto O. , Ngenegbo Uche C. , Obika Ifeanyi , Obikwelu Emmanuel M. , Nebe Obiageli J.
Published: September 2023

Over the past decade, Anambra State, Nigeria, has implemented mass administration of medicines (MAMs) to combat soil-transmitted helminthiasis (STH), a significant public health challenge in low-income regions. Nevertheless, these efforts have predominantly focused on pre-school and school-aged children, leaving a notable gap in understanding STH infection rates and the efficacy of these campaigns among secondary school adolescents, who have been excluded from this initiative. Our study aimed to address this critical knowledge gap by assessing soil-transmitted helminthiasis (STH) prevalence and contextual factors hindering effective control among adolescents in Anambra State, Nigeria. We actively engaged 443 adolescents with a mean age of 14 years in a school-based cross-sectional study in selected communities within the Anaocha Local Government Area from 8 February to 7 July 2023 following informed consent and assent procedures. Employing a stratified random sampling technique, we collected demographic data and assessed STH risk factors using a structured questionnaire hosted on the Kobo Toolbox platform. For quantitative analysis of STH infections, the Kato-Katz technique was used. Analysis was performed using SPSS version 25, incorporating descriptive statistics and multinomial logistic regression, with statistical significance set at p<0.05. Of the 443 (213 males (48.0%) and 230 females (52.0%) adolescents studied, the overall prevalence of STH observed was 35.2% (156/443).Ascaris lumbricoideswas the prevalent STH species (16.9%), followed byTrichuris trichiura(1.4%) and hookworm (0.5%). Only light-intensity infection was observed. Mixed infections were observed in 16.5% of adolescents, involvingA. lumbricoidesand hookworm (10.8%), followed byA. lumbricoidesandT. trichiura(3.2%) and all three STH (2.5%). The observed overall prevalence was not statistically significant with respect to gender (OR: 0.961; 95% CI: 0.651-1.420; p > 0.05) or age (OR: 0.686; 95% CI: 0.459-1.025; p>0.05). Class (grade level) (OR = 1.75, 95% CI: 1.25 - 2.45, p = 0.003), knowledge and transmission of STH infection (OR = 0.60, 95% CI: 0.42 - 0.86, p = 0.008), parental occupation (OR = 1.90, 95% CI: 1.35 - 2.67, p < 0.001), parents’ literacy level (OR = 0.68, 95% CI: 0.48 - 0.96, p = 0.027), and the type of toilet (OR = 2.15, 95% CI: 1.54 - 3.00, p < 0.001) were all significantly correlated with STH infection. These findings highlight the role of adolescents in sustaining soil-transmitted helminthiasis (STH) transmission. Coupled with school-based deworming expansion, innovative improvements in water, sanitation, hygiene, and awareness can provide a cost-effective, sustainable solution for combatting STH infections in Anambra State.
Global, regional, and national levels and trends in burden of urticaria: a systematic analysis for the global burden of disease 2019 study
Authors: Pu Yuanchun , He Liyu , Wang Xiangyu , Zhang Yaodong , Zhao Shidi , Fan Jinhai
Published: September 2023

Background

Urticaria causes a significant burden on individuals and society due to its pervasiveness. The aim of this study was to evaluate the burden of urticaria in different regions and nations by analyzing data from the Global Burden of Disease Study 2019 (GBD 2019) to provide a reference for healthcare policymakers.

Methods

Using the GBD 2019 database, this study analyzed incidence, prevalence, disability-adjusted life year (DALY), and corresponding ASRs and EAPC globally and in 204 countries and regions, and stratified the data by age, sex, and sociodemographic index (SDI).

Results

In 2019, the global incidence cases of urticaria increased to 114708912.2, the prevalence cases increased to 65139886.6, and the global DALY burden increased to 3898838.6. The distribution of the burden was markedly geographically heterogeneous. Burden indicators were generally higher in females than in males. There was a slight positive correlation between urticaria burden and regional SDI.

Interpretation

The burden of urticaria has been increasing globally from 1990 to 2019. This study identified multiple determinants that influence the burden of urticaria, such as geographic location and SDI. Despite the limitations of the GBD 2019 data, these discoveries provide a valuable resource for the development of future public health strategies aimed at reducing the burden of urticaria.
Stasis Imaging Predicts the Risk of Cardioembolic Stroke Related to Acute Myocardial Infarction
Authors: Rodríguez-González Elena , Martínez-Legazpi Pablo , Mombiela Teresa , González-Mansilla Ana , Delgado-Montero Antonia , Guzmán-De-Villoria Juan A. , Díaz-Otero Fernando , Prieto-Arévalo Raquel , Juárez Miriam , García del Rey Maria del Carmen , Fernández-García Pilar , Flores Oscar , Postigo Andrea , Yotti Raquel , García-Villalba Manuel , Fernández-Avilés Francisco , del Álamo Juan C , Bermejo Javier
Published: September 2023

Background

In the setting of ST-segment elevation myocardial infarction (STEMI), imaging-based biomarkers could be useful for guiding oral anticoagulation for primary prevention of stroke.

Objectives

To test the efficacy of intraventricular blood stasis imaging for predicting a composite primary endpoint of cardioembolic risk during the first 6 months after STEMI.

Methods

The Imaging Silent Brain Infarct in Acute Myocardial Infarction (ISBITAMI,NCT02917213) was a prospective clinical study including patients with a first STEMI, an EF ≤ 45% and without atrial fibrillation. Patients underwent ultrasound-based stasis imaging at enrollment followed by heart and brain magnetic resonance at 1-week and at 6-month visits. From the stasis maps, we calculated the average residence time,RT, of blood inside the LV and assessed its performance to predict the primary endpoint. Apical longitudinal strain was quantified by speckle tracking.

Results

A total of 68 patients were univocally assigned to the primary endpoint. Of them, 19 patients suffered one or more events: 3 strokes, 5 silent brain infarctions, and 15 mural thromboses. No systemic embolisms were observed.RT(OR: 3.28, 95% CI: 1.61-6.67, p=0.001) and apical strain (OR: 1.48, 95% CI: 1.14-1.92, p= 0.002) showed complementary prognostic value. The bivariate model showed a c-index= 0.84 (0.73-0.95) a negative predictive value of 1.00 (0.93-1.00) and positive predictive value of 0.45 (0.39 - 0.80). Results were confirmed in a multiple imputation sensitivity analysis. Conventional ultrasound-based metrics were of limited predictive value.

Conclusions

In patients with STEMI and LV systolic dysfunction in sinus rhythm, the risk of cardioembolic stroke can be accurately predicted by echocardiography combining stasis and strain imaging.
Accurate bacterial outbreak tracing with Oxford Nanopore sequencing and reduction of methylation-induced errors
Authors: Lohde Mara , Wagner Gabriel E. , Dabernig-Heinz Johanna , Viehweger Adrian , Braun Sascha D. , Monecke Stefan , Diezel Celia , Stein Claudia , Marquet Mike , Ehricht Ralf , Pletz Mathias W. , Brandt Christian
Published: September 2023

Our study investigated the effectiveness of Oxford Nanopore Technologies for accurate outbreak tracing by resequencing 33 isolates of a three-year-longKlebsiella pneumoniaeoutbreak with Illumina short read sequencing data as the point of reference.

We detected considerable base errors through cgMLST and phylogenetic analysis of genomes sequenced with Oxford Nanopore Technologies, leading to the false exclusion of some outbreak-related strains from the outbreak cluster. Nearby methylation sites cause these errors and can also be found in other species besidesK. pneumoniae. Based on this data, we explored PCR-based sequencing and a masking strategy, which both successfully addressed these inaccuracies and ensured accurate outbreak tracing. We offer our masking strategy as a bioinformatic workflow (MPOA is freely available on GitHub under the GNUv3 license:github.com/replikation/MPOA) to identify and mask problematic genome positions in a reference-free manner.

Our research highlights limitations in using Oxford Nanopore Technologies for sequencing prokaryotic organisms, especially for investing outbreaks. For time-critical projects that cannot wait for further technological developments by Oxford Nanopore Technologies, our study recommends either PCR-based sequencing or using our provided bioinformatic workflow. We would advise that read mapping-based quality control of genomes should be provided when publishing results.
Molecular pathways and cellular subsets associated with adverse clinical outcomes in overlapping immune-related myocarditis and myositis
Authors: Siddiqui Bilal A. , Palaskas Nicolas L. , Basu Sreyashi , Dai Yibo , He Zhong , Yadav Shalini S. , Allison James P. , Sheth Rahul , Tummala Sudhakar , Buja L. Maximilian , Bhattacharjee Meenakshi , Iliescu Cezar A. , Rawther-Karedath Anishia , Deswal Anita , Wang Linghua , Sharma Padmanee , Subudhi Sumit K.
Published: September 2023

Immune checkpoint therapies (ICTs) can induce life-threatening immune-related adverse events, including myocarditis and myositis, which are rare but often concurrent. The molecular pathways and immune subsets underlying these toxicities remain poorly understood. To address this need, we obtained heart and skeletal muscle biopsies for single-cell RNA sequencing in living patients with cancers treated with ICTs admitted to the hospital with myocarditis and /or myositis (overlapping myocarditis plus myositis, n=10; myocarditis-only, n=1) compared to ICT-exposed patients ruled out for toxicity utilized as controls (n=9) within 96 hours of clinical presentation. Analyses of 58,523 cells revealed clonally expanded CD8+T cells with a cytotoxic phenotype expressing activation/exhaustion markers in both myocarditis and myositis. Furthermore, the analyses identified a population of tissue-resident myeloid cells expressed FcγRIIIa, which is known to bind IgG and regulate complement activation. Immunohistochemistry of affected cardiac and skeletal muscle tissues revealed protein expression of pan-IgG and complement product C4d that were associated with the presence of high-titer serum autoantibodies against muscle antigens in a subset of patients. We further identified a population of inflammatory IL-1B+TNF+myeloid cells specifically enriched in myocarditis and associated with greater toxicity severity and poorer clinical outcomes. These results are the first to recognize these myeloid subsets in human immune-related myocarditis and myositis tissues and nominate new targets for investigation into rational treatments to overcome these high-mortality toxicities.

Graphical Abstract
A cerebellar disinhibitory circuit supports synaptic plasticity
Authors: Park Changjoo , Gim Jawon , Bahn Sangkyu , Kim Gyu Hyun , Im Yoonseok , Lee Sang-Hoon , Lee Kisuk , Kim Min-Soo , Lee Kea Joo , Kim Jinseop S.
Published: September 2023

How does the cerebellum learn how to control motion? The cerebellar motor learning critically depends on the long-term depression of the synapses between granule cells and Purkinje cells, which encode motor commands and inhibitory modifications to motor outputs, respectively, for simultaneous granule cell inputs and climbing fibre inputs, the latter of which encode the error signals1–3. However, recent studies have revealed that inhibitory inputs to Purkinje cells may disrupt long-term depression4–8, and it is not clear how long-term depression can occur without disruption. In search of a clue, we investigated the synaptic connectivity among the neurons reconstructed from serial electron microscopy images of the cerebellar molecular layer9,10. We discovered synapses between climbing fibres and a subset of inhibitory interneurons, which synapse onto the remaining interneurons, which in turn synapse onto Purkinje cells. Such connectivity redefines the interneuron types, which have been defined morphologically or molecularly11–13. Together with climbing fibres to Purkinje cell connections, those cell types form a feedforward disinhibitory circuit14. We argued that this circuit secures long-term depression by suppressing inhibition whenever climbing fibre input is provided and long-term depression needs to occur15, and we validated the hypothesis through a computational model. This finding implies a general principle of circuit mechanism in which disinhibition supports synaptic plasticity16,17.
SACNet: A Multiscale Diffeomorphic Convolutional Registration Network with Prior Neuroanatomical Constraints for Flexible Susceptibility Artifact Correction in Echo Planar Imaging
Authors: Zeng Zilong , Zhang Jiaying , Liang Xinyuan , Sun Lianglong , Zhang Yihe , Men Weiwei , Wang Yanpei , Chen Rui , Zhang Haibo , Tan Shuping , Gao Jia-Hong , Qin Shaozheng , Tong Qiqi , He Hongjian , Tao Sha , Dong Qi , He Yong , Zhao Tengda
Published: September 2023

Susceptibility artifacts (SAs), inevitable in brain diffusion MR (dMRI) scans acquired using single-shot echo planar imaging (EPI), severely compromise the accurate detection of human brain structure. Existing SA correction (SAC) methods offer inadequate correction quality and limited applicability across diverse datasets with varied acquisition protocols. To address these challenges, we proposed SACNet, a SAC framework based on unsupervised registration convolutional networks, featuring: i) a novel diffeomorphism regularization function to avoid unnatural SAC warps, modified from a potential well function; ii) an integration with prior neuroanatomical constraints and coarse-to-fine processing strategy to enables multi-scale geometric and intensity recoveries in severe distorted areas; iii) a unified registration framework that incorporates multiple phase-encoding (PE) EPI images and structural images, ensuring compatibility with both single- and inverse-PE protocols, with or without field maps. Utilizing simulated dMRI images and over 2000 brain scans from neonatal, child, adult and traveling participants, our method consistently demonstrates state-of-the-art correction performance. Notably, SACNet effectively reduces SAs-related multicenter effects compared to existing methods. We have developed user-friendly tools using containerization techniques, hope to facilitate SAC correction quality across extensive neuroimaging studies.
Deep learningversusgeometric morphometrics for archaeobotanical domestication study and subspecific identification
Authors: Bonhomme Vincent , Bouby Laurent , Claude Julien , Dham Camille , Gros-Balthazard Muriel , Ivorra Sarah , Jeanty Angèle , Pagnoux Clémence , Pastor Thierry , Terral Jean-Frédéric , Evin Allowen
Published: September 2023

Taxonomical identification of archaeological fruit and seed is of prime importance for any archaeobotanical studies. We compared the relative performance of deep learning and geometric morphometrics at identifying pairs of plant taxa. We used their seeds and fruit stones that are the most abundant recovered organs in archaeobotanical assemblages, and whose morphological identification, chiefly between wild and domesticated types, allow to document their domestication and biogeographical history. We used existing modern datasets of four plant taxa (date palm, barley, olive and grapevine) corresponding to photographs of two orthogonal views of their seeds that were analysed separately to offer a larger spectrum of shape diversity. On these eight datasets, we compared the performance of a deep learning approach, here convolutional neural networks (CNN), to that of a geometric morphometric approach, here outline analyses using elliptical Fourier transforms (EFT). Sample sizes were at minimum eight hundred seeds in each class, which is quite small when training deep learning models but of typical magnitude for archaeobotanical studies. Our objectives were twofold: i) to test whether deep learning can beat geometric morphometrics in taxonomic identification and if so, ii) to test which minimal sample size is required. We ran simulations on the full datasets and also on subsets, starting from 50 images in each binary class. For CNN networks, we deliberately used a candid approach relying on pre-parameterised VGG16 network. For EFT, we used a state-of-the art morphometrical pipeline. The main difference rests in the data used by each model: CNN used bare photographs where EFT used (x, y) outline coordinates. This “pre-distilled” geometrical description of seed outlines is often the most time-consuming part of morphometric studies. Results show that CNN beats EFT in most cases, even for very small datasets. We finally discuss the potential of CNN for archaeobotany, why outline analyses and morphometrics have not yet said their last word by providing quantitative descriptions, and how bioarchaeological studies could embrace both approaches, used in a complementary way, to better assess and understand the past history of species.
Complete substitution with modified nucleotides suppresses the early interferon response and increases the potency of self-amplifying RNA
Authors: McGee Joshua E. , Kirsch Jack R. , Kenney Devin , Chavez Elizabeth , Shih Ting-Yu , Douam Florian , Wong Wilson W. , Grinstaff Mark W.
Published: September 2023

Self-amplifying RNA (saRNA) will revolutionize vaccines andin situtherapeutics by enabling protein expression for longer duration at lower doses. However, a major barrier to saRNA efficacy is the potent early interferon response triggered upon cellular entry, resulting in saRNA degradation and translational inhibition. Substitution of mRNA with modified nucleotides (modNTPs), such as N1-methylpseudouridine (N1mΨ), reduce the interferon response and enhance expression levels. Multiple attempts to use modNTPs in saRNA have been unsuccessful, leading to the conclusion that modNTPs are incompatible with saRNA, thus hindering further development. Here, contrary to the common dogma in the field, we identify multiple modNTPs that when incorporated into saRNA at 100% substitution confer immune evasion and enhance expression potency. Transfection efficiency enhances by roughly an order of magnitude in difficult to transfect cell types compared to unmodified saRNA, and interferon production reduces by >8 fold compared to unmodified saRNA in human peripheral blood mononuclear cells (PBMCs). Furthermore, we demonstrate expression of viral antigensin vitroand observe significant protection against lethal challenge with a mouse-adapted SARS-CoV-2 strainin vivo. A modified saRNA vaccine, at 100-fold lower dose than a modified mRNA vaccine, results in a statistically improved performance to unmodified saRNA and statistically equivalent performance to modified mRNA. This discovery considerably broadens the potential scope of self-amplifying RNA, enabling entry into previously impossible cell types, as well as the potential to apply saRNA technology to non-vaccine modalities such as cell therapy and protein replacement.
Perspectives and Recommendations from Hospitalized Patients with Substance Use Disorders: A Qualitative Study
Authors: Balmuth Evan A. , Iyer Sonali , Scales David A. , Avery Jonathan
Published: September 2023

BACKGROUND

Individuals with substance use disorders (SUDs) are hospitalized in growing numbers. Stigma is pervasive among their hospital providers, and SUD management during medical admissions is often inadequate. However, little is known about how these patients perceive their care quality. In particular, few studies have explored their positive care perceptions or recommendations for improvement.

OBJECTIVE

To explore perspectives on positive aspects, negative aspects, and consequences of care, as well as recommendations for improvement among hospitalized patients with SUDs.

DESIGN AND PARTICIPANTS

We conducted semi-structured, in-depth bedside interviews (n= 15) with patients who have been diagnosed with a SUD and were admitted to medical or surgical floors of an urban academic medical center.

APPROACH

Interviews explored patients’ hospital experiences and recommendations for improvement. The interviews were audio-recorded, transcribed verbatim, and imported into NVivo software. Two reviewers independently coded the transcripts using interpretative phenomenological analysis and inductive thematic analysis according to grounded theory, and recurring themes were identified from the data. Patients’ demographic and clinical data were analyzed with descriptive statistics.

KEY RESULTS

Perceived clinical and emotional proficiency were the most important components of positive experiences, whereas perceived bias and stigmatized attitudes, clinical improficiency, and inhumane treatment were characteristic of negative experiences. Such care components were most consequential for patients’ emotional wellbeing, trust, and care quality. Recommendations for improving care included specific suggestions for initiating and promoting continued recovery, educating, and partnering in compassionate care.

CONCLUSIONS

Hospitalized patients with SUDs often experience lower quality and less compassionate care linked to pervasive stigma and poor outcomes. Our study highlights under-recognized perspectives from this patient population, including socioemotional consequences of care and recommendations grounded in lived experiences. By striving to advance our care in accordance with patients’ viewpoints, we can turn hospitalizations into opportunities for engagement and promoting recovery.