bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitrogen starvation response in hornworts and liverworts provides little evidence for complex priming to the cyanobiont
Authors: Yue Yuling , Sablok Gaurav , Neubauer Anna , Hyvönen Jaakko , Szövényi Péter
Published: May 2024

Mutualistic plant-microbe symbiotic interactions are thought to have evolved from a loose association between host plants and microbes when nutrients are limited. Therefore, the molecular network enabling intimate mutualistic plant-microbe symbioses may have evolved from a nutrient starvation response shared by all land plants. While the molecular link between nutrient status and symbiotic interaction is well-established, it remains poorly understood in some systems. This is especially true for the symbiotic associations between plants and cyanobacteria.

To test the conservation of the starvation network across land plants as well as to investigate the link between nutrient starvation and symbiosis initiation in the plant-cyanobacteria symbiosis, here we explore the transcriptional responses to nutrient starvation in two non-vascular plant species, a hornwortAnthoceros agrestisand a liverwortBlasia pusilla, forming plant-cyanobacteria endophytic symbioses. We observe a deep conservation of the systemic starvation response across land plants. However, very few if any components of the starvation network appear to be specific to cyanobacteria hosting plants, providing little evidence for extensive and specific priming to the cyanobiont. Moreover, we found that some bioactive molecules known to be important in initiating the plant-mycorrhiza and nodule-forming bacteria symbioses, may also have a similar role in plant-cyanobacteria symbioses.

Highlight

Our results suggest that the most critical step in establishing plant-cyanobacteria interactions using non-host plants is the attraction of the cyanobiont. This finding has significant impact on crop engineering.
Interferon-Induced PARP14-Mediated ADP-Ribosylation in p62 Bodies Requires an Active Ubiquitin-Proteasome System
Authors: Raja Rameez , Biswas Banhi , Abraham Rachy , Liu Hongrui , Chang Che-Yuan , Vu Hien , Leung Anthony K. L.
Published: May 2024

Biomolecular condensates are cellular compartments without enveloping membranes, enabling them to dynamically adjust their composition in response to environmental changes through post-translational modifications. A recent study has revealed that interferon-induced ADP-ribosylation (ADPr), which can be reversed by a SARS-CoV-2-encoded hydrolase, is enriched within a condensate. However, the identity of the condensate and responsible host ADP-ribosyltransferase remain elusive. Here, we demonstrate that interferon induces ADPr through transcriptional activation of PARP14, requiring both its physical presence and catalytic activity for condensate formation. Interferon-induced ADPr colocalizes with PARP14, and these PARP14/ADPr condensates contain key components of p62 bodies—including the selective autophagy receptor p62 and its binding partner NBR1, along with K48-linked and K63-linked polyubiquitin chains—but lack the autophagosome marker LC3B. Knockdown of p62 disrupts the formation of these ADPr condensates. Importantly, these structures are unaffected by autophagy inhibition but depend on both ubiquitin activation and proteasome activity. Taken together, these findings demonstrate that interferon triggers PARP14-mediated ADP-ribosylation in p62 bodies, which requires an active ubiquitin-proteasome system.
Diffusion within the synaptonemal complex can account for signal transduction along meiotic chromosomes
Authors: von Diezmann Lexy , Bristow Chloe , Rog Ofer
Published: May 2024

Meiotic chromosomes efficiently transduce information along their length to regulate the distribution of genetic exchanges within and between chromosomes. However, the mode of signal transduction remains unknown. Recently, a conserved chromosomal interface, the synaptonemal complex, was shown to be a biomolecular condensate, offering an attractive mechanism for signal transduction: diffusion of signaling molecules within the synaptonemal complex to allow transmission of information along each pair of chromosomes. Here, we test the feasibility of this mechanism in liveC. elegansgonads. Single-molecule tracking shows that a component of the synaptonemal complex (SYP-3) and a conserved regulator of exchanges (ZHP-3) both diffuse within the synaptonemal complex. However, ZHP-3 diffuses 4- and 9-fold faster than SYP-3 before and after crossovers formation, respectively. We use these measurements to parameterize a physical model for signal transduction. We find that ZHP-3, but not SYP-3, explores the lengths of chromosomes on the time scale of crossover maturation, consistent with a role in the spatial regulation of exchanges. Given the conservation of ZHP-3 paralogs across eukaryotes, we propose that diffusion within the synaptonemal complex may be a conserved mechanism of meiotic regulation. More broadly, our work explores how diffusion contained within condensates regulates crucial cellular functions.
At the roots of interference control: Conflict task in rats reveals the commonalities of onto- and phylo-genetic development
Authors: Poitreau Julien , Ambroggi Frédéric , Hasbroucq Thierry , Sargolini Francesca , Burle Boris
Published: May 2024

Responding to internal goals and filtering irrelevant environmental cues is essential for adapted behavior. To better understand their phylogenetic evolution, we explored the underlying mechanisms in rats, thanks to the adaptation of a well-established conflict task in Humans. Besides mean performance, state of the art data analysis based on distribution analysis and formal modeling (diffusion model adapted to conflict tasks that proved very powerful in Humans) revealed mechanisms similar to the ones observed in human adults, grounding any theoretical explanation into an evolutionary perspective. Besides, the dynamics of the underlying processes in this simple conflict task resembles the ones observed in human children performing a more challenging conflict task, including the tendency to loose goals. The present study bridges the gap between onto- and phylo-genetic development of cognitive control, opening new perspectives to understand both their functional and neural implementation.
Quantifying Population-level Neural Tuning Functions Using Ricker Wavelets and the Bayesian Bootstrap
Authors: Ahumada Laura , Panitz Christian , Traiser Caitlin , Gilbert Faith , Ding Mingzhou , Keil Andreas
Published: May 2024

Experience changes the tuning of sensory neurons, including neurons in retinotopic visual cortex, as evident from work in humans and non-human animals. In human observers, visuo-cortical re-tuning has been studied during aversive generalization learning paradigms, in which the similarity of generalization stimuli (GSs) with a conditioned threat cue (CS+) is used to quantify tuning functions. This work utilized pre-defined tuning shapes reflecting prototypical generalization (Gaussian) and sharpening (Difference-of-Gaussians) patterns. This approach may constrain the ways in which re-tuning can be characterized, for example if tuning patterns do not match the prototypical functions or represent a mixture of functions. The present study proposes a flexible and data-driven method for precisely quantifying changes in neural tuning based on the Ricker wavelet function and the Bayesian bootstrap. The method is illustrated using data from a study in which university students (n = 31) performed an aversive generalization learning task. Oriented gray-scale gratings served as CS+ and GSs and a white noise served as the unconditioned stimulus (US). Acquisition and extinction of the aversive contingencies were examined, while steady-state visual event potentials (ssVEP) and alpha-band (8-13 Hz) power were measured from scalp EEG. Results showed that the Ricker wavelet model fitted the ssVEP and alpha-band data well. The pattern of re-tuning in ssVEP amplitude across the stimulus gradient resembled a generalization (Gaussian) shape in acquisition and a sharpening (Difference-of-Gaussian) shape in an extinction phase. As expected, the pattern of re-tuning in alpha-power took the form of a generalization shape in both phases. The Ricker-based approach led to greater Bayes factors and more interpretable results compared to prototypical tuning models. The results highlight the promise of the current method for capturing the precise nature of visuo-cortical tuning functions, unconstrained by the exact implementation of prototypical a-priori models.

Highlights

Tuning functions are a common way for describing sensory responses, primarily in the visual cortex.

The quantification and interpretation of tuning functions has faced computational and conceptual problems.

We demonstrated how the Ricker function can be used as a simple and interpretable way for measuring tuning functions.

We applied a Ricker function together with a Bayesian Bootstrap approach across a gradient of stimulus features in a generalization conditioning task to characterize visual tuning in the human EEG data.
Functional Activity, Functional Connectivity and Complex Network Biomarkers of Progressive Hyposmia Parkinson’s Disease with No Cognitive Impairment: Evidences from Resting-state fMRI Study
Authors: Geng Lei , Cao Wenfei , Zuo Juan , Yan Hongjie , Wan Jinxin , Sun Yi , Wang Nizhuan
Published: May 2024

Background

Olfactory dysfunction stands as one of the most prevalent non-motor symptoms in the initial stage of Parkinson’s disease (PD). Nevertheless, the intricate mechanisms underlying olfactory deficits in Parkinson’s disease still remain elusive.

Methods

This study collected rs-fMRI data from 30 PD patients (15 with severe hyposmia (PD-SH) and 15 with no/mild hyposmia (PD-N/MH)) and 15 healthy controls (HC). To investigate functional segregation, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were utilized. Functional connectivity (FC) analysis was performed to explore the functional integration across diverse brain regions. Additionally, the graph theory-based network analysis was employed to assess functional networks in PD patients. Furthermore, Pearson correlation analysis was conducted to delve deeper into the relationship between the severity of olfactory dysfunction and various functional metrics.

Results

Firstly, PD patients showed significantly higher ALFF values in the superior temporal gyrus compared to HC, especially in the PD-SH group versus PD-N/MH. Meanwhile, ALFF values in this region negatively correlated with olfactory testing scores. Secondly, PD patients had higher ReHo in middle temporal gyrus and superior frontal gyrus than HC, especially PD-SH. Meanwhile, olfactory scores negatively correlated with these ReHo values. Thirdly, we observed a negative correlation between superior cerebellar-insula connectivity and olfactory scores, suggesting a neural circuit link to olfactory dysfunction. Lastly, the PD patients’ brain networks consistently showed small-world attributes, with the PD-N/MH group having significantly higher nodal betweenness in the superior cerebellum than the PD-SH group. There’s also a positive link between superior cerebellum’s betweenness and olfactory scores. Additionally, there is a notable difference in the node degree of the superior temporal gyrus when comparing the PD-SH group to the PD-N/MH group.

Conclusion

Using fMRI, our study analyzed brain function in PD-SH, PD-N/MH, and HC groups, revealing impaired segregation and integration in PD-SH and PD-N/MH. We hypothesize that changes in temporal, frontal, occipital, and cerebellar activities, along with aberrant cerebellum-insula connectivity and node degree and betweenness disparities, may be linked to olfactory dysfunction in PD patients.
Contribute to balance, wire in accordance: Emergence of backpropagation from a simple, bio-plausible neuroplasticity rule
Authors: Fan Xinhao , Mysore Shreesh P
Published: May 2024

Over the past several decades, backpropagation (BP) has played a critical role in the advancement of machine learning and remains a core method in numerous computational applications. It is also utilized extensively in comparative studies of biological and artificial neural network representations. Despite its widespread use, the implementation of BP in the brain remains elusive, and its biological plausibility is often questioned due to inherent issues such as the need for symmetry of weights between forward and backward connections, and the requirement of distinct forward and backward phases of computation. Here, we introduce a novel neuroplasticity rule that offers a potential mechanism for implementing BP in the brain. Similar in general form to the classical Hebbian rule, this rule is based on the core principles of maintaining the balance of excitatory and inhibitory inputs as well as on retrograde signaling, and operates over three progressively slower timescales: neural firing, retrograde signaling, and neural plasticity. We hypothesize that each neuron possesses an internal state, termed credit, in addition to its firing rate. After achieving equilibrium in firing rates, neurons receive credits based on their contribution to the E-I balance of postsynaptic neurons through retrograde signaling. As the network’s credit distribution stabilizes, connections from those presynaptic neurons are strengthened that significantly contribute to the balance of postsynaptic neurons. We demonstrate mathematically that our learning rule precisely replicates BP in layered neural networks without any approximations. Simulations on artificial neural networks reveal that this rule induces varying community structures in networks, depending on the learning rate. This simple theoretical framework presents a biologically plausible implementation of BP, with testable assumptions and predictions that may be evaluated through biological experiments.
EHR-based Case Identification of Pediatric Long COVID: A Report from the RECOVER EHR Cohort
Authors: Botdorf Morgan , Dickinson Kimberley , Lorman Vitaly , Razzaghi Hanieh , Marchesani Nicole , Rao Suchitra , Rogerson Colin , Higginbotham Miranda , Mejias Asuncion , Salyakina Daria , Thacker Deepika , Dandachi Dima , Christakis Dimitri A , Taylor Emily , Schwenk Hayden , Morizono Hiroki , Cogen Jonathan , Pajor Nathan M , Jhaveri Ravi , Forrest Christopher B. , Bailey L. Charles
Published: May 2024

Objective

Long COVID, marked by persistent, recurring, or new symptoms post-COVID-19 infection, impacts children’s well-being yet lacks a unified clinical definition. This study evaluates the performance of an empirically derived Long COVID case identification algorithm, or computable phenotype, with manual chart review in a pediatric sample. This approach aims to facilitate large-scale research efforts to understand this condition better.

Methods

The algorithm, composed of diagnostic codes empirically associated with Long COVID, was applied to a cohort of pediatric patients with SARS-CoV-2 infection in the RECOVER PCORnet EHR database. The algorithm classified 31,781 patients with conclusive, probable, or possible Long COVID and 307,686 patients without evidence of Long COVID. A chart review was performed on a subset of patients (n=651) to determine the overlap between the two methods. Instances of discordance were reviewed to understand the reasons for differences.

Results

The sample comprised 651 pediatric patients (339 females,Mage= 10.10 years) across 16 hospital systems. Results showed moderate overlap between phenotype and chart review Long COVID identification (accuracy = 0.62, PPV = 0.49, NPV = 0.75); however, there were also numerous cases of disagreement. No notable differences were found when the analyses were stratified by age at infection or era of infection. Further examination of the discordant cases revealed that the most common cause of disagreement was the clinician reviewers’ tendency to attribute Long COVID-like symptoms to prior medical conditions. The performance of the phenotype improved when prior medical conditions were considered (accuracy = 0.71, PPV = 0.65, NPV = 0.74).

Conclusions

Although there was moderate overlap between the two methods, the discrepancies between the two sources are likely attributed to the lack of consensus on a Long COVID clinical definition. It is essential to consider the strengths and limitations of each method when developing Long COVID classification algorithms.
Menstrual hygiene management among reproductive-aged women with disabilities in Bangladesh
Authors: Khan Md Nuruzzaman , Khanam Shimlin Jahan , Chowdhury Atika Rahman , Hossain Rashed , Kabir Md Awal , Alam Md Badsha
Published: May 2024

Background

Women with disabilities in low- and middle-income countries face unique challenges in managing menstruation, affecting their health, dignity, and quality of life.

Objective

This study explored menstrual hygiene management (MHM) practices among reproductive-aged women with disabilities in Bangladesh and its impact on social participation.

Methods

We analyzed data from 51,535 women from the 2019 Multiple Indicator Cluster Survey (MICS). The outcome variables were: (i) material used to manage blood flow while menstruating (appropriate, inappropriate), (ii) availability of a private place for washing and changing menstruation rags (yes, no), and (iii) impacted in attendance of social activities, school, or work during menstruation (yes, no). Disability status was considered as major explanatory variable and categorized as no disabilities, moderate disabilities, and severe disabilities. Associations of outcome variables with explanatory variable were determined using a multilevel multinomial logistic regression model adjusted for individual-level factors, household-level factors, and community-level factors.

Results

Among the sample, 2.7% reported severe disability and 19.2% moderate disabilities, with vision-related disabilities (12.2%) being the most prevalent, followed by cognitive (9.5%) and walking disabilities (8.2%). Overall, 4% reported using inappropriate materials for menstrual flow, rising to 8.0% among those with severe disabilities and 5.8% for moderate disabilities. Women with moderate to severe disabilities had 33-47% lower odds of using appropriate materials and 34-44% lower odds of having a private place to change at home. Additionally, women with severe disabilities were 1.66 times more likely to report that menstruation impacted their social activities.

Conclusion

Women with disabilities in Bangladesh face significant barriers to effective MHM. Addressing these issues requires targeted interventions, including disability-inclusive menstrual health education, improved access to menstrual products and sanitation facilities, and community initiatives to reduce stigma.
LagaEcosystem, Species Entanglements and the Risk of Zoonotic Disease Transmission: A Multi-Site, Multi-Method Ethnographic Study
Authors: Omia Dalmas , Oketch Dismas , Njoroge Ruth , Ngere Isaac , Gachohi John , Waiguru Samuel , Magarre Abdulai G. , Khamadi Samoel Ashimosi , Nuismer Scott L , Njeru John Mwaniki , Bodha Boku , Nyaga Nazaria , Njaanake Humphrey , Jaoko Walter , Njenga Kariuki , Osoro Eric
Published: May 2024

Dry riverbeds, also calledIaga, are a complex ecosystem of multispecies interactions between livestock, humans, microorganisms, and their environment. Despitelaga’sOne Health entanglement of species and environment, few studies have explored the risks of transmission of diseases through direct herd-herd or herd-human contact or indirect contact with fomites surrounding thelaga. This study focuses on ethnographic and epidemiological investigations onlagaswithin Kenya. The study deploys qualitative multimethod-walking interviews, in-depth interviews, key informant interviews, focus group discussions and observations to collect the data from Marsabit and Kajiado Counties in Kenya. Results point to the comingling of infected and healthy herds, cross-livestock species mixing, sharing of watering troughs, and feeding dogs placental and parturition materials at the herd level. The human transmission risks include non-protective parturition assistance, the use of camel urine as an antiseptic substance, humans sharing animal-watering troughs, and consuming non-processed milk. Further, the fomites comprise contaminated excreta, infected placental materials onlagastones, deposition of infected aborted fetuses on thelagabody, and bacteria in the sand that end up ingested or inhaled as dust during dry seasons. The study concludes that intensified water insecurity due to climate variability will deepen multispecies interactions at thelagagiven that it holds a lifeline in drylands for pastoralists, hence, heightening brucellosis transmission risks. The study’s results recommend a reinvention of brucellosis preventive measures that consider the pathogen flux withinlagasystems and multispecies interactions. Such an approach should consider the multidimensional-clinical, environmental, and cultural co-production of solutions where preventive behaviors are prioritized.
Genal: A Python Toolkit for Genetic Risk Scoring and Mendelian Randomization
Authors: Rivier Cyprien A. , Clocchiatti-Tuozzo Santiago , Huo Shufan , Torres-Lopez Victor , Renedo Daniela , Sheth Kevin , Falcone Guido J. , Acosta Julian N.
Published: May 2024

Here we present Genal, a python module for population genetic analyses. It includes functionalities for cleaning and formatting Single Nucleotide Polymorphism (SNP)-level data, clumping, lifting, SNP association testing, polygenic risk scoring, and mendelian randomization analyses, all within a single module. It was designed with user-friendliness in mind, aiming to reduce the programming skills threshold required for medical scientists to perform genetic epidemiology studies. Genal eliminates the need to interact with the command line and switch between multiple R packages with different requirements, making it considerably more accessible to a wide range of researchers. Genal draws on concepts from several well-established tools, ensuring that users have access to rigorous statistical techniques in the intuitive Python environment.
Functional Assessment of Protein Variants in Structured Domains by Fluorescence Cross-Correlation Spectroscopy
Authors: Mateu-Regué Àngels , Mariani Luca , Bagger Frederik Otzen , Bose Muthiah , Nielsen Finn Cilius
Published: May 2024

With the expanding catalogue of novel disease-genes, there is an increasing need to establish the significance of potential disease-causing variants. Based on the idea that pathogenic variants in structured protein domains disturb folding and association with macromolecular assemblies, we employed Fluorescence Correlation and Cross-Correlation Spectroscopy (FCS and FCCS) to assessin vivoprotein complex formation. Since the molecular underpinning of BRCA-associated breast and ovarian cancers is well defined and data from a recent genome editing screening allowed us to compare variant binding data with a reliable functional HRD test in addition to ClinVar and AlphaMissense data, we examined the binding of mutated wild-type BRCA1 or isolated RING and BRCT domains to BARD1 and RBBP8, respectively. The results demonstrate that FCCS, whether applied to full-length BRCA1 in live cells and/or to isolated domains in cellular lysates identified pathogenic BRCA1 RING or BRCT domain variants. We moreover demonstrate the feasibility of employing FCCS for analysis of HNPCC-related factor MSH2 and MEN1 factor Menin variants in combination with DNA mismatch repair factor MSH6 and transcription factor JUND, respectively. We propose that FCCS may be an appealing complement to current clinical procedures for classifying variants, for many monogenic diseases given its generic nature and ease of use.
Impact of adherence and stringency on the effectiveness of lockdown measures: a modelling study
Authors: Brunekreef Joren , Teslya Alexandra , Buskens Vincent , Nunner Hendrik , Kretzschmar Mirjam
Published: May 2024

During the COVID-19 pandemic, lockdowns were a widely used strategy to reduce disease transmission. However, there was much debate about the optimal level of strictness and duration of lockdowns. This study considers how lockdowns impact public health opinions, which in turn influence adherence to and effectiveness of these measures. We developed an agent-based simulation model to study the impact of health-related opinions on the effectiveness of lockdowns in controlling disease spread. The model simulates infection spread and health opinion dynamics among individuals connected through a network of contacts and incorporates feedback loops between epidemic variables and opinion dynamics. We simulated different scenarios of lockdown implementation by varying a threshold value of prevalence when a lockdown is initiated and the stringency of the lockdown. We found that quickly imposing a lockdown with high stringency is the most effective at reducing infection spread, provided that there is a certain degree of adherence to the lockdown among the population. Furthermore, stricter lockdowns minimize fatigue with respect to the imposed measures, since the duration of a lockdown is shorter on average in this scenario. Such lockdown policies can therefore be a beneficial, high-impact tool in containing epidemic spread, especially when supplemented by information interventions maintaining the adherence to lockdown measures.

Author summary

Lockdowns were a widely used strategy to curb disease transmission during the COVID-19 pandemic. However, the effectiveness of such measures depends on the population’s adherence to the regulations. Long and strict lockdowns may lower this adherence as the population experiences ‘fatigue’ with the regulations. In our study, we model the interplay between lockdowns, disease transmission, and health-related opinions in a population network.

We tested various lockdown scenarios by altering strictness of measures on the one hand, and lockdown initiation times based on disease prevalence rates on the other hand. Our findings show that swift, stringent lockdowns are the most effective in reducing infections, particularly with strong public compliance. Additionally, stricter lockdowns tend to reduce fatigue as they are generally shorter.

These results highlight that prompt, rigorous lockdown policies, supported by strategies to maintain public adherence, are most efficient in controlling epidemics. Furthermore, effective communication to ensure community cooperation may enhance the success of these measures.
Prospective follow-up of New York City residents with e-cigarette, or vaping product use-associated lung injury—2020–2021
Authors: Tannert Niang Kathryn M. , Grasso Aviva B. , Debchoudhury Indira , Bushman Dena , Jasek John P. , Fairclough Monique A. , Van Oss Katherine R. , Chamany Shadi , LaSane Kendall D. , Franklin Sharraine M. , Talati Achala K.
Published: May 2024

Background

A multistate outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) occurred in 2019. Because of EVALI’s novelty and severity, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) prospectively assessed sequelae among NYC residents who received an EVALI diagnosis in 2019.

Methods

Using existing NYC EVALI surveillance data, DOHMH attempted contact with all living residents who received an EVALI diagnosis in 2019 and conducted 3 waves of telephone interviews during April 2020–March 2021. Interview questions were adapted from the Centers for Disease Control and Prevention’s EVALI case report form and validated surveys. Baseline differences between respondents and nonrespondents were assessed with Chi-square and Fisher’s exact tests; clinical and behavioral characteristics and open-ended responses were summarized.

Results

In 2019, 53 NYC residents received an EVALI diagnosis; 33 (67%), 14 (29%), and 18 (37%) of 49 living residents participated in the first, second, and third interviews, respectively. Interviews occurred after outpatient diagnosis (6%) or hospital discharge (94%), at a median of 8, 11, and 17 months for each wave. Respondents (N = 33) and nonrespondents (N = 16) did not differ by sex, age, hospitalization status or length. Respondents were mostly male (70%), had a median age of 23 years (range: 16–63 years), and all reported using vaping or e-cigarette products (vaping) with tetrahydrocannabinol (88%), nicotine (49%), or cannabidiol (9%) before diagnosis. Respiratory (first and second interviews) and gastrointestinal (third interviews) symptoms were most commonly reported. Sixteen respondents (49%) reported any new diagnosis during follow-up. Fifteen to 29% of respondents reported vaping at each interview; 58%–93% reported recent non-vaped cannabinoid use.

Conclusion

NYC residents with EVALI reported symptoms throughout the follow-up period, and approximately half reported newly diagnosed health conditions.
Magnetization Transfer MRI of intragastric milk digestion: a feasibility study in humans
Authors: Mayar Morwarid , Terenzi Camilla , van Duynhoven John P.M. , Smeets Paul A.M.
Published: May 2024

Gastric milk protein (MP) coagulation has been extensively studied usingin vitroand animal models. Yet, verifying these results in humans remains essential. Recently, we demonstrated that1H Magnetization Transfer (MT) MRI can be used for the assessment of gastric MP coagulationin vitro.In the present follow-up study, we assessed the feasibility of using MT MRI for monitoring MP coagulationin vivoin humans. Twelve healthy adults underwent MRI scans before and after ingesting 300 g of low- or high-pasteurized skim milk (LPSM or HPSM, respectively). We assessed coagulation and gastric emptying (GE) dynamics by deriving the MT ratio (MTR),the total gastric content (TGC), semi-solid, and liquid volumes. TheMTRvalues increased during digestion for both milk products, indicating a decrease in protein molecular mobility and a concomitant increase in the degree of coagulation. Prolonged heating of milk did not affect theMTR(p = 0.15), but resulted in higher TGC volumes (MD 40.3 mL, 95% CI [25.5-55.1], p = 0.044) with a trend towards greater semi-solid (p = 0.056) or liquid (p = 0.065) volumes. These findings suggest that prolonged heating of milk leads to slower GE. We thus showed that by combining MT with conventional anatomical MRI both MP coagulation and GE dynamics, and thereby the impact of heating on gastric milk digestion, can be assessedin vivoin humans. Our work underpins the feasibility of using MRI as a non-invasive imaging tool for studying the effect of food processing and composition on gastric digestion.
Monitoring sodium content in packaged foods sold in the Americas and compliance with the Updated Regional Sodium Reduction Targets
Authors: Yang Yahan , Flexner Nadia , Tiscornia Maria Victoria , Guarnieri Leila , Blanco-Metzler Adriana , Núñez-Rivas Hilda , Roselló-Araya Marlene , Arévalo-Rodríguez Paola , Kroker-Lobos Maria Fernanda , Diez-Canseco Francisco , Meza-Hernández Mayra , Yabiku-Soto Kiomi , Saavedra-Garcia Lorena , Allemandi Lorena , Nederveen Leo , L’Abbé Mary R.
Published: May 2024

Background

Sodium reduction is a cost-effective measure to prevent noncommunicable diseases. The World Health Organization (WHO) established a target of a 30% relative reduction in mean population intake of sodium by 2025. The Pan American Health Organization (PAHO) published sodium reduction targets for packaged foods in 2015, expanding and updating the targets in 2021 to help Member States with its efforts in reducing population sodium intake.

Objective

This study examined the current sodium levels in packaged foods among five countries in the Americas and monitored cross-sectional and longitudinal compliance with the sodium targets from 2015 to 2022.

Methods

Food labels were systematically collected from the main supermarkets in five countries in the Americas region in 2022. Sodium levels per 100g and per kcal for collected food labels in 16 PAHO categories and 75 subcategories were analyzed and compared against the Updated Regional Targets. Further analysis of three countries that have longitudinal data for 2015-2016, 2017-2018 and 2022 was conducted to compare sodium per 100 g against the 2015 PAHO Targets.

Results

A total of 25,569 food items were analyzed. Overall,‘processed meat and poultry’had the highest sodium levels, although there were large variations within categories. 47% and 45% of products met the sodium per 100g and per kcal 2022 targets, respectively. Peru had the highest compliance, whereas Panama had the lowest for both targets. Among Argentina, Costa Rica and Peru, the proportion of foods meeting the 2015 PAHO lower targets were 48, 53 and 61% for 2015-2016, 2017-2018 and 2022, respectively.

Conclusions

This study showed that around half of the examined foods met their respective sodium targets and there have been small improvements in compliance over time. Further efforts are required to reach the WHO’s global sodium reduction goal by 2025, such as implementation of mandatory sodium reduction targets and front-of-pack labelling regulations.
Development and Validation of a Diagnostic Prediction Rule for Osteopenia
Authors: Janwittayanuchit Thammabhorn , Kaewboonlert Naritsaret , Tangkanjanavelukul Pornthep , Phattaramarut Kitirat , Thongdee Pattama
Published: May 2024

Objectives

To triage patients with a high likelihood of osteopenia before referring them for a standard bone mass density test for diagnosis.

Introduction

Osteopenia defined by low bone mineral density, is a precursor for osteoporosis and is primarily associated with aging-linked natural bone loss in adulthood. The model and findings can be used to adopt an inclusive screening and swift treatment model that can work in most settings where resources are limited.

Methods

We developed a diagnostic prediction rule based on clinical characteristics. A retrospective cohort of 798 patients who were going to be diagnosed with osteopenia or osteoporosis, within January-September 2022. The multivariable logistic regression to assess potential predictors. The logistic coefficients were transformed as a risk-based scoring system. The internally validation was performed using a bootstrapping procedure.

Results

The model initially included seven predictors: sex, age, height, weight, body mass index, diabetes mellitus, and estimated glomerular filtration rate. However, after using backward elimination for model reduction, only three predictors—sex, age, and weight—were retained in the final model. The discrimination performance was assessed with the area under the receiver operating characteristic curve (AuROC); it was 0.779 (95%CI 0.74-0.82), and the calibration plot showed good calibration. For internal validation, bootstrap resampling was utilized, yielding an AuROC of 0.768 (95% CI 0.73-0.81), indicating robust performance of the model.

Conclusions

This study developed and internally validated the Osteopenia Simple Scoring System. This clinical risk score could be one of the important tools for diagnosing osteopenia and allocating resources in resource-limited settings.
Postoperative Surveillance Adherence in Colorectal Cancer Patients at Urban Medical Center: is it Adequate?
Authors: Alnasarat Ahmad , Darian Talin R. , Shahait Awni , Baldawi Mohanad , Mostafa Gamal
Published: May 2024

Aim

To examine the adherence rate to surveillance guidelines after curative resection of colorectal cancer (CRC) and the impact of demographic factors.

Methods

Data was collected retrospectively including demographics, stage at diagnosis, and adherence to surveillance guidelines as recommended by the US Multi-Society Task Force (USMSTF) guidelines, for colorectal cancer (CRC) patients who underwent curative surgical resection between 2005 and 2014 in a tertiary academic medical center.

Results

A total of 124 patients were included (Male /female, 56.5%/ 43.5%), African American 109 (87.9%), and 70 patients (56.5%) had Medicare/Medicaid insurance. Overall, Appropriate clinical evaluation twice per year for 3 years following surgery was completed in 78 (63%) of patients. A total of 56 (45%) had carcinoembryonic antigen (CEA) levels checked twice a year for 3 years. Surveillance colonoscopy 1 year postoperatively occurred in 64 (51.6%), and 37 (29.8%) had a second colonoscopy 3 years postoperatively. Abdomen/pelvis CT scan was obtained in 90 (72.5%) at 1 year post-operatively. In the entire cohort, strict adherence to post-recession surveillance only occurred in 46 (37.1%). There was no correlation between adherence to surveillance and gender (p=0.184), race (p=0.118), or insurance type (p=0.51).

Conclusion

Adherence to surveillance after curative resection of CRC was inadequate regardless of socioeconomic, medical insurance, or race. Measures should be taken to identify barriers and improve compliance with guidelines.

What is already known on this topic?

Effective surveillance after colorectal cancer surgery is essential, yet many patients fail to follow recommended guidelines. Existing research highlights disparities in CRC outcomes based on race, socioeconomic status, and insurance coverage, affecting early detection and treatment.

What this study adds

Our study reveals a 37.1% adherence rate to surveillance guidelines among CRC patients in an urban medical center, unaffected by gender, race, or insurance status. This challenges previous assumptions about demographic disparities in post-resection care.

How this study might affect research, practice, or policy

The study highlights the need for interventions to improve adherence rate to CRC surveillance. Future research, clinical practices, and policy initiatives should focus on overcoming barriers to ensure equitable and effective follow-up care.
A CT-based radiomics approach for CD8+ lymphocytes infiltration stratification in patients with non-small cell lung cancer
Authors: Zerka Fadila , Felfli Mehdi , Voyton Charles M , Thinnes Alexandre , Jacques Sebastien , Liu Yan , Iannessi Antoine
Published: May 2024

Background

Accurate prediction of tumor microenvironment is crucial for optimizing decision making throughout cancer treatment process. Current biopsy or surgical-based approaches to assess tumor microenvironment are limited by their invasiveness and tumor heterogeneity. The present study aimed to investigate the association of computed tomography radiomics features and CD8+ lymphocyte infiltration levels for patients with non-small cell lung cancer.

Materials and Methods

283 patients with CT imaging and RNA-Seq data were collected from open-source data repositories. The study included three independent cohorts of non-small cell lung cancer patients, with one serving as the training set and the other two as external test sets. 1246 CT radiomics features were extracted. Three discriminative texture features were used to train the AI model.

Results

The model, trained on discriminative features, achieved a mean area under the curve AUC-ROC of 0.71(±0.17 std) on the training data. The AUC-ROC of the model on the two independent test sets is 0.67 (95% CI: 51%, 80%) on TCGA and 0.64 (95% CI: 51%, 74%) on LUNG3.

Conclusion

CT texture features can differentiate patients with high from low CD8+ lymphocyte infiltration levels. These features can non-invasively analyze the whole tumor and aid in the identification of patients that can respond to immunotherapy.

Tweetable abstract

Texture radiomics features on CT scans can aid in stratifying CD8+ lymphocyte infiltration levels for patients with NSCLC.
The diagnostic accuracy of the point-of-care urine dipstick test in detecting urinary tract infection among symptomatic patients in Nairobi County, Kenya
Authors: Onyango Hellen A. , Sloan Derek J , Keenan Katherine , Kesby Mike , Ngugi Caroline , Gitonga Humphrey , Hammond Robert
Published: May 2024

Background

Urinary tract infections (UTIs) are among the most frequently diagnosed bacterial infections and constitute a large proportion of workload in clinical microbiology laboratories. Urine culture is the confirmatory test for UTI. However, most primary care settings routinely use the more rapid, less labour-intensive dipstick. This study assesses the characteristics of a urine dipstick test in predicting a positive urine culture and how best it can be used in resource constrained settings despite its limitations.

Method

A cross-sectional study was conducted at two level-V health facilities in Nairobi County, Kenya. Adults and children presenting with clinical symptoms of UTI were enrolled after obtaining written informed consent. Midstream urine samples were collected. Urinary dipstick was used to identify Nitrites (NIT) and leucocyte esterase (LE) production. Urine was cultured on Cystine Lactose Electrolyte Deficient agar, blood agar and MacConkey agar; and incubated at 370C for 24 hours. Urine cultures with pure bacterial colony counts of ≥104cfu/ml were classified as “positive” for UTI.

Results

Of a total of 552 participants enrolled into the study, 124 (23%) were urine culture positive. Prior medication use was associated with culture negativity. With urine culture as the reference standard, urinary dipstick sensitivity was poor overall (using either LE+ or NIT+ to confer a positive dipstick result still only achieved sensitivity of 66.9%). Using combined NIT+ and LE+ to confer a positive dipstick result had the highest specificity (99.2%), alongside a positive predictive value of 91.1%, and a positive likelihood ratio of 35.6. A NIT+ test alone showed highest concordance with urine culture results (percentage agreement: 86%) but still had a Cohen’s Kappa value of only 0.5, conferring weak agreement overall.

Conclusion

Dipstick test is a poor surrogate of urine culture. However, the test may be suitable as a ‘rule-out’ test to exclude UTI, and avoid antibiotic prescription, when both NIT and LE are negative. Although dipstick continues to be in use in resource constrained settings, poor concordance with urine culture results highlights a need for better near patient tests to diagnose UTI and guide antibiotic decision-making.
MAIN CAUSES OF MEDICINE STOCK-OUTS IN MAURITANIA: A QUALITATIVE STUDY
Authors: Ag Ahmed Mohamed Ali , Coulibaly Issa , Ravinetto Raffaella , Buitrago Verónica Trasancos , Dujardin Catherine
Published: May 2024

The number of medicine stock-outs (MSOs) is increasing globally. In Mauritania, they are recurring, although, to our knowledge, no study has yet been conducted to determine the causes. Therefore, this qualitative study aims to identify the main local or national causes of stock-outs to provide a common understanding and guide policy-makers towards corrective actions. The study was carried out in five health districts and at the regional and central levels. The samples were purposive. Two focus groups and twenty semi-structured individual interviews were held with 38 participants, including health professionals, managers from the Central Purchasing Office for Essential Medicines and Consumables (CAMEC), the Pharmacy and Laboratory Department (DPL) and the Ministry of Health (MoH). All interviews were recorded and transcribed. A thematic content analysis was carried out. Our findings indicate the national causes of MSOs at three healthcare system levels (operational, regional, and central). They were grouped into five categories: insufficient human resource capacity (number of staff, training, retention), communication and coordination problems between stakeholders, logistical constraints (transport, storage), financial constraints, inadequate forecasting of needs, and complex procurement procedures. These causes of MSOs are interconnected, and many could be addressed locally through solutions initiated and led by the Mauritanian authorities. To address MSOs sustainably, we suggest and discuss some possible actions, including reforms to improve CAMEC’s governance and accountability and, more broadly, to strengthen the various pillars of the local health and pharmaceutical system.
The role of Construction of Healthcare Consortium on the allocation of human resources for primary care resources and its equity in China
Authors: Li Shijie , Liao Changze , Zhang Shengli
Published: May 2024

Objectives

This study aims to measure the effect of Construction of Healthcare Consortium (CHC) on the allocation and equity of human resources (HR) for primary health care (PHC) in China, at the same time, it provides some data to support the government’s policies improvement in the next stage.

Methods

Changes in the equity of allocation of HR for PHC by population are demonstrated through a three-stage approach to inequality analysis that includes the Gini coefficient (G), the Theil index (T), the concentration index (CI) and concentration curve. The GM(1,1) model is used to project the trend of resources from 2021 to 2030.

Results

Volume of HR for PHC accelerates at an average rate of growth following the release of CHC in the 2016. whilst some regions have seen their G and T rise between 2012 and 2016, their levels of inequality of allocation for resource shave gradually declined in the years following 2016, but there are exceptions, with the regions of northeast and northwest seeing the opposite. Eastern and northern region account for a larger contribution to intra-regional inequality. Concentration indices and concentration curves indicate that HR for PHC is related to economic income levels. GM (1, 1) projects an increasing trend in resources from 2021 to 2030, but with variations in average growth rates in different regions.

Conclusions

The inequality of human resources for primary health care in China is low, however, the inequality between regions has not been eliminated. We still need to take a long-term view to monitor the impact of CHC on the allocation of HR for PHC and its equity in China.
Examining the impact of maternal experiences of domestic violence on adolescent mental health disorders in India
Authors: Gourisankar Amritha , Ravi Preethi , Kalokhe Ameeta S. , Hall Rachel Waford , Vaidya Nilakshi , Sharma Eesha , Holla Bharath , Basu Debasish , Bharath Rose Dawn , Chakrabarti Amit , Desrivieres Sylvane , Hickman Matthew , Kartik Kamakshi , Ghattu Krishnaveni , Kalyanaraman Kumaran , Kuriyan Rebecca , Murthy Pratima , Orfanos Dimitri Papadopoulos , Purushottam Meera , Kurpad Sunita Simon , Singh Rajkumar Lenin , Singh Roshan Lourembam , Subodh Bhagyalakshmi Nanjayya , Toledano Mireille B , Benegal Vivek , Schumann Gunter , Kalyanram Kartik ,   cVEDA Consortium
Published: May 2024

Background

Domestic violence (DV) is experienced by one in three women in India and is linked to poor mental health outcomes. We hypothesize that maternal experiences of DV can have negative impacts on the mental health of their children. Previous studies have demonstrated this link in Western countries, however culturally specific manifestations of DV and mental health disorders and socio-cultural differences in parent-child relationships and home environments necessitate deeper understanding of the impacts of maternal experiences of DV on children in the Indian context.

Methods

This study presents a secondary analysis of data collected from a seven-center study in urban and rural India examining mental health disorders among adolescents aged 12-17 years and psychological, physical, and sexual abuse affecting their mothers. The Indian Family Violence and Control Scale (IFVCS) was used to examine experiences of DV among mothers and the Mini International Neuropsychiatric Interview–Kid (MINI-Kid) was used to examine mental health outcomes among adolescents. Multivariate analyses examined the associations between maternal DV and adolescent mental disorders.

Results

Data from 2,784 adolescent-mother pairs were analyzed. In bivariate analyses, maternal experiences of physical, psychological, and sexual abuse were significantly associated with adolescent common mental disorders including anxiety and depression (p<0.05). After adjusting for adolescent gender, site, and education status in the multivariate analysis, physical, sexual, and any DV were significantly associated with adolescent anxiety disorders and common mental disorders. Physical abuse was significantly associated with adolescent depressive disorders.

Conclusions

These results suggest that exposure to maternal DV significantly impacts adolescent mental health in India and underscore the need to develop trauma-informed school programs and enhance DV prevention for women in India.