bluuebunny/crossref_metadata_2025 huggingface dataset:
Brief Report: HIV-1 Resistance Analysis of Participants With HIV-1 and Hepatitis B Initiating Therapy With Bictegravir/Emtricitabine/Tenofovir Alafenamide or Dolutegravir Plus Emtricitabine/Tenofovir Disoproxil Fumarate: A Subanalysis of ALLIANCE Data
Authors: D'Antoni Michelle L. , Andreatta Kristen , Chang Silvia , Cox Stephanie , Hindman Jason T. , Avihingsanon Anchalee , Martin Hal , VanderVeen Laurie A. , Callebaut Christian
Published: April 2024

Background:

In the phase 3 ALLIANCE study, both bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and dolutegravir plus emtricitabine/tenofovir disoproxil fumarate (DTG + F/TDF) achieved high rates of HIV-1 RNA suppression through week 96 in adults with HIV-1 and hepatitis B virus initiating treatment (NCT03547908). In this study, we quantify preexisting HIV-1 resistance, evaluate its effect on HIV-1 virologic suppression, and describe postbaseline HIV-1 resistance through week 96.

Methods:

Preexisting HIV-1 resistance was assessed by historical and/or screening genotyping. HIV-1 RNA suppression to <50 copies (c)/mL at week 96 was assessed by the preexisting resistance category. Postbaseline resistance was assessed in participants with HIV-1 RNA ≥200 c/mL through week 96.

Results:

Primary nucleoside/nucleotide reverse transcriptase inhibitor, nonnucleoside reverse transcriptase inhibitor, and protease inhibitor resistance substitutions were present at baseline in 4 (1.7%), 19 (7.9%), and 5 (2.1%) of 241 participants, respectively. Virologic suppression rates were high, irrespective of preexisting primary resistance substitutions, including M184I. Six participants (3 per group) had confirmed HIV-1 RNA ≥200 c/mL and did not resuppress to <50 c/mL while on study drugs; none of the 5 with postbaseline resistance data had treatment-emergent primary resistance substitutions. One participant on DTG + F/TDF with multiple virologic failures and documented nonadherence by pill count had treatment-emergent K70E and M184V/I, and subsequently resuppressed.

Conclusion:

In people with HIV-1 and hepatitis B virus treated with first-line B/F/TAF or DTG + F/TDF, preexisting HIV-1 resistance was uncommon and did not affect virologic suppression. No treatment-emergent HIV-1 resistance occurred with B/F/TAF, further supporting the high barrier to resistance of this regimen.
Brief Report: Protease Inhibitors Versus Nonnucleoside Reverse Transcriptase Inhibitors and the Risk of Cancer Among People With HIV
Authors: Coburn Sally B. , Pimentel Noel , Leyden Wendy , Kitahata Mari M. , Moore Richard D. , Althoff Keri N. , Gill M. John , Lang Raynell , Horberg Michael A. , D'Souza GypsyAmber , Hussain Shehnaz K. , Dubrow Robert , Novak Richard M. , Rabkin Charles S. , Park Lesley S. , Sterling Timothy R. , Neugebauer Romain S. , Silverberg Michael J. ,   for the North American AIDS Cohort Collaboration on Research and Design of the International Epidemiologic Databases to Evaluate AIDS
Published: April 2024

Background:

The effect of initial antiretroviral therapy (ART) class on cancer risk in people with HIV (PWH) remains unclear.

Setting:

A cohort study of 36,322 PWH enrolled (1996–2014) in the North American AIDS Cohort Collaboration on Research and Design.

Methods:

We followed individuals from ART initiation (protease inhibitor [PI]-based, nonnucleoside reverse transcriptase inhibitor [NNRTI]-based, or integrase strand transfer inhibitor [INSTI]-based) until incident cancer, death, loss-to-follow-up, December 31, 2014, 85 months (intention-to-treat analyses [ITT]), or 30 months (per-protocol [PP] analyses). Cancers were grouped (nonmutually exclusive) as follows: any cancer, AIDS-defining cancers (ADC), non-AIDS-defining cancers (NADC), any infection-related cancer, and common individual cancer types. We estimated adjusted hazard ratios (aHR) comparing cancer risk by ART class using marginal structural models emulating ITT and PP trials.

Results:

We observed 17,004 PWH (954 cancers) with PI-based (median 6 years follow-up), 17,536 (770 cancers) with NNRTI-based (median 5 years follow-up), and 1782 (29 cancers) with INSTI-based ART (median 2 years follow-up). Analyses with 85-month follow-up indicated no cancer risk differences. In truncated analyses, the risk of ADCs (aHR 1.33; 95% CI: 1.00, 1.77 [PP analysis]) and NADCs (aHR 1.23; 95% CI: 1.00 to 1.51 [ITT analysis]) was higher comparing PIs vs. NNRTIs.

Conclusions:

Results with longer-term follow-up suggest being on a PI-based versus NNRTI-based ART regimen does not affect cancer risk. We observed shorter-term associations that should be interpreted cautiously and warrant further study. Further research with a longer duration of follow-up that can evaluate INSTIs, the current first-line recommended therapy, is needed to comprehensively characterize the association between ART class and cancer risk.
MORTALITY AND ASSOCIATED FACTORS AMONG INTENSIVE CARE UNIT ADMITTED ADULT PATIENTS WITH MECHANICAL VENTILATION IN ETHIOPIA: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Alamaw Addis Wondmagegn , Abebe Gebremeskel Kibret , Abate Biruk Beletew , Tilahun Befkad Derese , Yilak Gizachew , Birara Wagaw Abebe , Azmeraw Molla , Habtie Tesfaye Engdaw , Zemariam Alemu Birara
Published: April 2024

Introduction: The global demand for intensive care has risen, given its effectiveness in lowering mortality rates. Mechanical ventilation (MV) is integral to intensive care but introduces risks such as ventilator-associated complications. Ethiopia experiences a high intensive care unit (ICU) mortality rate. Objective: This systematic review and meta-analysis aim to comprehensively synthesize evidence on the mortality of adults undergoing MV in Ethiopia and identify associated factors. Methods: The study extensively searched databases and gray literature for research on MV outcomes, trends, and associated factors in adult ICUs. Adhering to the 2020 PRISMA checklist, a systematic review and meta-analysis sought to establish the mortality rate and key determinants among adult ICU patients on MV. The search incorporated keywords and MeSH terms, excluding studies with unsound methodologies or missing data. Data extraction, quality assessment, and analysis followed established protocols, including the JBI tool for methodological quality evaluation. STATA version 17.0 facilitated analysis, assessing heterogeneity, publication bias, and performing sensitivity and meta-regression analyses. Results: The pooled mortality rate among adult ICU patients undergoing MV was 48.61% (95% CI: 40.82, 56.40%). Significant mortality-contributing factors included medical diagnosis, Glasgow Coma Scale score, sepsis/septic shock, sedation use, multiple-organ dysfunction syndrome, and cardiovascular disease. Although some pooled odds ratios seemed insignificant, closer examination revealed significant associations in individual studies. Conclusion: The study underscores the urgent need for further research, improved ICU infrastructure, and healthcare personnel training in Ethiopia to enhance outcomes for mechanically ventilated patients. Identified factors offer valuable insights for targeted interventions, guiding tailored treatment strategies to reduce mortality. This study contributes to understanding mortality and associated factors in MV patients, informing initiatives to improve critical care outcomes in Ethiopia.
CIRCVMA21-RELATED PATHWAY ALLEVIATES LIPOPOLYSACCHARIDE-INDUCED HK-2 CELL INJURY
Authors: Li Fuzhu , Fu Hongyun , Zeng Linna , Liu Pingping
Published: April 2024

Background: It is reported that circVMA21 has an inhibition effect on sepsis-induced acute kidney injury (AKI). Therefore, the underlying molecular mechanisms of circVMA21 in AKI are worthy of further investigation. Material and Methods: Lipopolysaccharide (LPS) was used to induce HK2 cell injury. CircVMA21, miR-337-3p and ZEB2 expression was tested by qRT-PCR. Cell growth was detected by CCK8 assay, EdU assay, and flow cytometry. Protein levels were examined by western blot. The levels of inflammatory factors and oxidative stress markers were measured to evaluate cell inflammatory response and oxidative stress. RNA relationship as verified by dual-luciferase reporter assay, RIP assay, and RNA pull-down assay. Results: CircVMA21 had decreased expression in AKI patients. Overexpressed circVMA21 alleviated LPS-induced HK2 cell inflammation, apoptosis, and oxidative stress. Moreover, circVMA21 sponged miR-337-3p, and miR-337-3p targeted ZEB2. The inhibitory effect of circVMA21 on LPS-induced HK2 cell injury was reversed by miR-337-3p overexpression, and ZEB2 overexpression abolished the promotion effect of miR-337-3p on LPS-induced HK2 cell injury. Conclusions: CircVMA21 could inhibit LPS-induced HK2 cell injury via miR-337-3p/ZEB2 axis.
DEVELOPMENT AND VALIDATION OF A MODEL FOR PREDICTION OF SEPTIC SHOCK IN NEONATES WITH SEPSIS
Authors: Liu Chunmei , Wang Yanggan
Published: April 2024

Purpose: This study aimed to develop and validate a model for prediction of septic shock in neonates with sepsis. Materials and methods: This retrospective study included early-onset septic neonates in the Renmin Hospital of Wuhan University between January 2017 and June 2021. The neonates were divided into the training set and the validation set in a ratio of 7:3 and further categorized into septic shock group and none-shock group according to presence or absence of shock symptoms. Results: A total of 406 septic neonates were enrolled, including 217 in septic shock group. Sex (odds ratio [OR] = 0.092, 95% confidence interval [CI]: 0.012 to 0.683, P = 0.020), C-reactive protein at 6 h (OR = 8.475, 95% CI: 3.154 to 22.774, P < 0.001), serum amyloid A at 6 h (OR = 1.179, 95% CI: 1.094 to 1.269, P < 0.01), white blood cells at 6 h (OR = 0.173, 95% CI: 0.092 to 0.326, P < 0.001), platelets at 6 h (OR = 0.985, 95% CI: 0.975 to 0.995, P < 0.001), and Ca2+ at 6 h (OR = 1.44 × 1011, 95% CI: 2.70 × 106 to 7.70 × 1015, P < 0.001) were identified as independent risk factors for septic shock and were further included in the nomogram. The areas under the receiver operator characteristic curve were 0.873 and 0.920 in training and validation sets, respectively. Conclusions: A predictive model for early diagnosis of septic shock in neonates was developed and initially validated in this study, allowing for timely intervention.
Somatostatin Versus Octreotide for Prevention of Postoperative Pancreatic Fistula: The PREFIPS Randomized Clinical Trial
Authors: Gaujoux Sébastien , Regimbeau Jean-Marc , Piessen Guillaume , Truant Stéphanie , Foissac Frantz , Barbier Louise , Buc Emmanuel , Adham Mustapha , Fuks David , Deguelte Sophie , Muscari Fabrice , Sulpice Laurent , Vaillant Jean-Christophe , Schwarz Lilian , Sa Cunha Antonio , Muzzolini Milena , Dousset Bertrand , Sauvanet Alain ,   Collaborators
Published: April 2024

Objective:

Pharmacological prevention of postoperative pancreatic fistula (POPF) after pancreatectomy is open to debate. The present study compares clinically significant POPF rates in patients randomized between somatostatin versus octreotide as prophylactic treatment.

Methods:

Multicentric randomized controlled open study in patient’s candidate for pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) comparing somatostatin continuous intravenous infusion for 7 days versus octreotid 100 μg, every 8 hours subcutaneous injection for 7 days, stratified by procedure (PD vs DP) and size of the main pancreatic duct (>4 mm) on grade B/C POPF rates at 90 days based on an intention-to-treat analysis.

Results:

Of 763 eligible patients, 651 were randomized: 327 in the octreotide arm and 324 in the somatostatin arm, with comparable the stratification criteria - type of surgery and main pancreatic duct dilatation. Most patients had PD (n=480; 73.8%), on soft/normal pancreas (n=367; 63.2%) with a nondilated main pancreatic duct (n=472; 72.5%), most often for pancreatic adenocarcinoma (n=311; 47.8%). Almost all patients had abdominal drainage (n=621; 96.1%) and 121 (19.5%) left the hospital with the drain in place (median length of stay=16 days). A total of 153 patients (23.5%) developed a grade B/C POPF with no difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (χ2 test, P=0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis.

Conclusion:

Continuous intravenous somatostatin is not statistically different from subcutaneous octreotide in the prevention of grade B/C POPF after pancreatectomy.

Findings:

In the PREFIPS Randomized Clinical Trial including 651 patients, a total of 153 patients (23.5%) developed a grade B/C POPF with no significant difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (χ2 test, P=0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis.
Large Language Models to process, analyze, and synthesize biomedical texts – a scoping review
Authors: Doneva Simona Emilova , Qin Sijing , Sick Beate , Ellendorff Tilia , Goldman Jean-Philippe , Schneider Gerold , Ineichen Benjamin Victor
Published: April 2024

The advent of large language models (LLMs) such as BERT and, more recently, GPT, is transforming our approach of analyzing and understanding biomedical texts. To stay informed about the latest advancements in this area, there is a need for up-to-date summaries on the role of LLM in Natural Language Processing (NLP) of biomedical texts. Thus, this scoping review aims to provide a detailed overview of the current state of biomedical NLP research and its applications, with a special focus on the evolving role of LLMs. We conducted a systematic search of PubMed, EMBASE, and Google Scholar for studies and conference proceedings published from 2017 to December 19, 2023, that develop or utilize LLMs for NLP tasks in biomedicine. LLMs are being applied to a wide array of tasks in the biomedical field, including knowledge management, text mining, drug discovery, and evidence synthesis. Prominent among these tasks are text classification, relation extraction, and named entity recognition. Although BERT-based models remain prevalent, the use of GPT-based models has substantially increased since 2023.
Cross species modeling reveals a role for the unfolded protein response in shaping the transcriptional reaction toMycobacterium tuberculosisinfection
Authors: Pullen Krista M. , Finethy Ryan , Ko Seung-Hyun B. , Reames Charlotte J. , Sassetti Christopher M. , Lauffenburger Douglas A.
Published: April 2024

Numerous blood mRNA signatures have been developed to diagnose tuberculosis (TB) disease. The utility of these signatures in diverse populations depends on the inclusion of ubiquitously expressed features, such as type 1 interferon (IFN) production and innate immune cell activities. As a result, these signatures are generally insensitive to heterogeneous responses between individuals. Designing more effective therapies will require understanding the diverse mechanisms underlying pathogenesis by associating them with appropriate preclinical animal models. To address this critical animal-to-human gap, we applied a modeling framework, Translatable Components Regression, which is designed to account for biological heterogeneity by identifying multiple orthogonal axes of variation that are common to humans and animal models. Our framework was capable of distinguishing human active TB from latent TB infection using a model derived from murine data. This discrimination was based on differential expression of numerous biological pathways in addition to the common IFN and neutrophil signatures. Prominent among these predictive pathways was protein translation, which we show is a feature of the Mtb infection-induced Unfolded Protein Response (UPR) in macrophages. We show that this cellular stress pathway controls a variety of immune-related functions in Mtb-infected mouse macrophages, suggesting a possible causative role during the development of TB disease.

Significance Statement

Despite tuberculosis being one of the top causes of global mortality, the mechanisms that control the progression of disease are still not fully understand. Here we leverage a systems-level modeling approach that incorporates transcriptomics data across thousands of genes from both a traditional tuberculosis mouse model and human clinical samples to implicate a previously unappreciated mechanism in pathogenesis, the unfolded protein response. We validate these findings in a mouse macrophage model and pinpoint which branch of the unfolded protein response might be activated during tuberculosis infection. These insights, originally derived from our cross-species model, may allow us to better understand human tuberculosis pathogenesis and potentially identify therapeutic targets to prevent active tuberculosis.
Real-time visualization reveals Mycobacterium tuberculosis ESAT-6 disrupts phagosome via fibril-mediated vesiculation
Authors: Koiri Debraj , Nandi Mintu , Abik Hameem P M , Bhausaheb Aher Jayesh , Meher Geetanjali , Behura Assirbad , Kumar Akhil , Choudhary Vineet , Choubey Sandeep , Saleem Mohammed
Published: April 2024

Mycobacterium tuberculosis (Mtb)evades host defense by hijacking and rupturing the phagosome, enabling it to escape to the host cytosol for its survival. ESAT-6, a secreted virulence protein ofMtb, is known to be critical for phagosome rupture. However, the mechanism of ESAT-6-mediated disruption of the phagosomal membrane remains unknown. Usingin vitroreconstitution and numerical simulations, we discover that ESAT-6 polymerization remodels and vesiculates phagosomal membrane. In contrast to the pore formation triggered by a bilayer-spanning conformation, we find that the binding of ESAT-6 to the phagosomal membrane is shallow. Such shallow insertion leads to membrane shape transition leading to tubular and bud-like deformations on the membrane in a concentration-dependent manner, facilitated by the reduction in membrane tension and compressibility modulus. Strikingly, our observations suggest that ESAT-6 polymerizes in bulk and on the membrane, bothin vitroand in macrophage. Numerical simulations demonstrate that growing fibrils generate both radial and tangential forces causing local remodeling and shape transition of the membrane. Using micropipette aspiration, we quantitatively show that ESAT-6 bound tensed membrane undergoes local changes in membrane curvature and lipid phase separation, also facilitated by the direct contact of the bacteria inside the phagosome. Nonetheless, the vesiculation of the buds is primarily driven by the forces exerted by the polymerization of ESAT-6. Such ESAT-6 mediated vesiculation induces apoptosis and host cell death in a concentration and time-dependent manner that promotes infection. Overall, the findings provide mechanistic insights into the long-standing question of phagosome disruption byMtbfor its escape.
MetaX: A peptide centric metaproteomic data analysis platform using Operational Taxa-Functions (OTF)
Authors: Wu Qing , Ning Zhibin , Zhang Ailing , Zhang Xu , Sun Zhongzhi , Figeys Daniel
Published: April 2024

Metaproteomics analyzes the functional dynamics of microbial communities by identifying peptides and mapping them to the most likely proteins and taxa. The challenge in this field lies in seamlessly integrating taxonomic and functional annotations to accurately represent the contributions of individual microbial taxa to functional diversity. We introduce MetaX, a comprehensive tool for analyzing taxa-function relationships in metaproteomics by mapping peptides to their lowest common ancestors and assigning functions based on proportional thresholds, ensuring accurate peptide-level mappings. Importantly, MetaX introduces the Operational Taxa-Functions (OTF), a new conceptual unit for exploring microbial roles and interactions within ecosystems. Additionally, MetaX extends traditional taxonomic classification by adding a genome level below the species level, enhancing the accuracy of function attribution to specific genomes. We demonstrated MetaX by reanalyzing metaproteomic data from gut microbiomes exposed to various sweeteners, achieving results similar to traditional protein analysis. Furthermore, using the peptide-centric approach and OTF, we observed thatParabacteroides distasonissignificantly responds to certain sweeteners, highlighting its role in modifying specific metabolic functions. With its intuitive, user-friendly interface, MetaX facilitates detailed study of the complex interactions between microbial taxa and their functions in metaproteomics. It enhances our understanding of microbial roles in ecosystems and health.
Behavioral and cortical arousal from sleep, muscimol-induced coma, and anesthesia by direct optogenetic stimulation of cortical neurons
Authors: Mao Rong , Cavelli Matias Lorenzo , Findlay Graham , Driessen Kort , Peterson Michael J , Marshall William , Tononi Giulio , Cirelli Chiara
Published: April 2024

The cerebral cortex is widely considered part of the neural substrate of consciousness. However, while several studies have demonstrated that stimulation of subcortical nuclei can produce EEG activation and restore consciousness, so far no direct causal evidence has been available for the cortex itself. Here we tested in mice whether optogenetic activation of cortical neurons in posterior parietal cortex (PtA) or medial prefrontal cortex (mPFC) is sufficient for arousal from three behavioral states characterized by progressively deeper unresponsiveness: sleep, a coma-like state induced by muscimol injection in the midbrain, and deep sevoflurane-dexmedetomidine anesthesia. We find that cortical stimulation always awakens the mice from both NREM sleep and REM sleep, with PtA requiring weaker/shorter light pulses than mPFC. Moreover, in most cases light pulses produce both cortical activation (decrease in low frequencies) and behavioral arousal (recovery of the righting reflex) from brainstem coma, as well as cortical activation from anesthesia. These findings provide evidence that direct activation of cortical neurons is sufficient for behavioral and/or cortical arousal from sleep, brainstem coma, and anesthesia.
Divergence in a Eukaryotic Transcription Factor’s co-TF Dependence Involves Multiple Intrinsically Disordered Regions Affecting Activation and Autoinhibition
Authors: Snyder Lindsey F. , O’Brien Emily M. , Zhao Jia , Liang Jinye , Bruce Baylee J. , Zhang Yuning , Zhu Wei , Cassier Thomas J. , Schnicker Nicholas J. , Zhou Xu , Gordân Raluca , He Bin Z.
Published: April 2024

Combinatorial control by multiple transcription factors (TFs) is a hallmark of eukaryotic gene regulation. Despite its prevalence and crucial roles in enhancing specificity and integrating information, the mechanisms behind why eukaryotic TFs depend on one another, and whether such interdependence evolves, are not well understood. We exploit natural variation in co-TF dependence in the yeast phosphate starvation (PHO) response to address this question. In the model yeastSaccharomyces cerevisiae, the main TF, Pho4, relies on the co-TF Pho2 to regulate ∼28 genes. In a related yeast pathogen,Candida glabrata, its Pho4 exhibits significantly reduced Pho2 dependence and has an expanded target set of ∼70 genes. Biochemical analyses showedC. glabrataPho4 (CgPho4) binds to the same consensus motif with 3-4-fold higher affinity than ScPho4 does. A machine-learning-based prediction and yeast one-hybrid assay identified two Intrinsically Disordered Regions (IDRs) in CgPho4 that boost the activity of the main activation domain but showed little to no activity on their own. We also found evidence for autoinhibition behind the co-TF dependence in ScPho4. An IDR in ScPho4 next to its DNA binding domain was found to act as a double-edged sword: it both allows for enhanced activity with Pho2, and inhibits Pho4’s activity without Pho2. This study provides a detailed molecular picture of how co-TF dependence is mediated and how its evolution, mainly driven by IDR divergence, can lead to significant rewiring of the regulatory network.
Linear infrastructure and associated wildlife accidents create an ecological trap for an apex predator and scavenger
Authors: Singh Navinder J , Etienne Michelle , Spong Göran , Ecke Frauke , Hörnfeldt Birger
Published: April 2024

Animals can be caught in an “ecological trap” when they select for seemingly attractive habitats at the expense of their fitness. Such maladaptive behaviour is often a consequence of human induced rapid changes in animals’ natal environment such as building of energy and transportation infrastructure. We tested the ecological trap hypotheses for human created linear infrastructure on a widely distributed apex predator and a scavenger – the Golden eagle (Aquila chrysaetos), whose range spans across the entire northern hemisphere. Roads and railways create novel and attractive feeding subsidies through traffic induced mortality of other species, while powerline areas provide perching or nesting sites and scavenging opportunities from electrocuted or collision-killed birds. These conditions lead to negative demographic consequences for eagles. We used integrated step selection functions for habitat selection and movement behaviour with ten years of data from 74 GPS-tracked Golden Eagles (36 adult and 38 immature) in Fennoscandia. To measure habitat attractiveness, we use wildlife traffic accident statistics on major wildlife species including the eagles, and mortality of five GPS- tracked eagles to show demographic consequences. Eagles selected for linear features all year round and across entire study region. Individuals also searched and sat alongside roads and railway lines more frequently. Immature eagles selected roads and railway sites more consistently compared to adults and showed learning behaviour with age. We discuss implications of these findings for conservation and population ecology of apex predators and scavengers and their potential evolutionary implications. We suggest that rapid removal of carcasses from roads and tracks is urgently needed to avoid this trap for many raptor and scavenger species throughout the world and develop methods and approaches to reduce wildlife traffic accidents all together.
The cytoplasm of living cells can sustain transient and steady intracellular pressure gradients
Authors: Malboubi Majid , Esteki Mohammad Hadi , Korsak Lulu I T. , Petrie Ryan J. , Moeendarbary Emad , Charras Guillaume
Published: April 2024

Understanding the physical basis of cellular shape change in response to both internal and external mechanical stresses requires understanding cytoplasmic rheology. At subsecond time-scales and micron length-scales, cells behave as fluid-filled sponges in which shape changes necessitate intracellular fluid redistribution. However, whether these cytoplasmic poroelastic properties play an important role in cellular mechanical response over length-scales and time-scales relevant to cell physiology remains unclear. Here, we investigated whether and how a localised deformation of the cell surface gives rise to transient intracellular flows spanning several microns and lasting seconds. Next, we show that pressure gradients induced in the cytoplasm can be sustained over several minutes. We found that stable pressure gradients can arise from the combination of cytoplasmic poroelasticity and water flows across the membrane. Overall our data indicate that intracellular cytosolic flows and pressure gradients may play a much greater role than currently appreciated, acting over time- and length-scales relevant to mechanotransduction and cell migration, signifying that poroelastic properties need to be accounted for in models and states of the cell.
Inflammatory profiles in sputum and blood of people with TB with and without HIV coinfection
Authors: Auld Sara C , Queiroz Artur T L , Araujo-Pereira Mariana , Maenetje Pholo , Mofokeng Nomsa , Mngomezulu Lerato , Masilela Duduzile , Dobosh Brian , Tirouvanziam Rabindra , Kornfeld Hardy , Andrade Bruno B , Bisson Gregory P
Published: April 2024

Although tuberculosis (TB) remains a major killer among infectious diseases and the leading cause of death for people with HIV, drivers of immunopathology, particularly at the site of infection in the lungs remain incompletely understood. To fill this gap, we compared cytokine profiles in paired plasma and sputum samples collected from adults with pulmonary TB with and without HIV. We found that people with pulmonary TB with HIV had significantly higher markers of inflammation in both plasma and sputum than those without HIV; these differences were present despite a similar extent of radiographic involvement. We also found that the strength and direction of correlations between biomarkers in the blood and lung compartments differed by HIV status and people with HIV had more positive correlations than those without HIV. Future studies can further explore these differences in inflammation by HIV status across the blood and lung compartments and seek to establish how these profiles may be associated with long-term outcomes and lung health after completion of TB treatment.
An approach to finding specific forms of dysbiosis that associate with different disorders
Authors: Williams Jonathan , Williams Inga , Morten Karl , Kenyon Julian
Published: April 2024

Background

Many disorders display dysbiosis of the enteric microbiome, compared with healthy controls. Different disorders share a pattern of dysbiosis that may reflect ‘reverse causation’, due to non-specific effects of illness-in-general. Combining a range of disorders into an ‘aggregate non-healthy active control’ (ANHAC) group should highlight such non-specific dysbiosis. Differential dysbiosis between the ANHAC group and specific disorders may then reflect effects of treatment or bowel dysfunction, or may potentially be causal. Here, we illustrate this logic by testing if individual genera can differentiate an ANHAC group from two specific diagnostic groups.

Methods

We constructed an ANAHC group (n=17) that had 14 different disorders. We then used random forest analyses to test differential dysbiosis between the ANHAC group and two other disorders that have no known pathology, but: (i) symptoms of illness (Myalgic Encephalomyelitis / Chronic Fatigue Syndrome – ME/CFS – n = 38); or (ii) both illness and bowel dysfunction (ME/CFS comorbid with Irritable Bowel Syndrome – IBS – n=27).

Results

Many genera differentiated the ANHAC group from co-morbid IBS. However, only two genera - Roseburia and Dialister – discriminated the ANHAC group from ME/CFS.

Conclusions

Different disorders can associate with specific forms of dysbiosis, over-and-above non-specific effects of illness-in-general. Bowel dysfunction may contribute to dysbiosis in IBS via reverse causation. However, ME/CFS has symptoms of illness-in-general, but lacks known pathology or definitive treatment that could cause dysbiosis. Therefore, the specific dysbiosis in ME/CFS may be causal. [230 words]

Contribution to the field

Many disorders associate with enteric dysbiosis. The pattern of dysbiosis is largely consistent between unrelated disorders, which suggests that it mainly reflects non-specific secondary effects of illness-in-general (e.g. due to changes in activity levels, or diet). However, faecal microbiome transplantation (FMT) can be therapeutic in some disorders. This implies that unique features of dysbiosis may cause those specific disorders. Here, we propose a way to assess causal effects of dysbiosis, by testing if individual genera can discriminate individual disorders from an ‘aggregate non-healthy active control’ (ANHAC) group. Dysbiosis in the ANHAC group can control for non-specific effects of illness-in-general on the microbiome and so highlight potentially-causal forms of dysbiosis in specific disorders. This approach may provide insight into pathogenetic mechanisms of individual disorders and help to design specific forms of FMT to counteract them.
User testing on Foods with Function Claims labelling in Japan : An attempt to establish an integrated evaluation system for the usefulness of health information materials
Authors: Yamamoto Michiko , Yamamoto Ken , Takano-Ohmuro Hiromi , Yamamoto Rain , Saruwatari Junji
Published: April 2024

The saturation of self-care products in the market is coupled with inadequate information on their safe usage. In Japan, although foods with function claims (FFC) are prevalent, their labelling falls short in quality and effectiveness as health information, impeding consumer comprehension and proper utilization. Hence, it is imperative to establish a system that assesses the efficacy of labelling information from both provider and user perspectives. From providers’ or healthcare professionals’ perspective, we already developed a Communication Index to assess FFC labelling, which we utilized to evaluate five FFC products. Those products achieved a proficiency level of approximately 70%, falling below the acceptance criteria. Particularly, challenges were identified in understanding some of the terms and locating important information on the labels. In this study, we conducted user-testing from the user perspective for five same FFC labels to evaluate them using semi-structured interviews with 50 participants of diverse ages and sexes. A passing criterion for comprehension was set as ≥90% correct responses to all questions. Of the five FFC products, one passed the user-testing criterion with a 2-min response time; however, none passed the 1-min response time test. The proportions of correct answers were notably low for questions on diet and allergies (each 50-90%), concomitant medications (50-100%), storage (30-100%), and handling (30-100%). Participants’ comments revealed a lack of familiarity with FFC, highlighting that the terms and text in the labelling were confusing and overly technical. User-testing provides valuable insights for improving FFC labelling, thereby ensuring safe and appropriate use by aligning with consumers’ understanding and perceptions. We assessed FFC label information from both the provider and user perspectives, but neither yielded satisfactory results. Consequently, the implementation of an integrated system capable of evaluating FCC labels as health information material from both perspectives would be necessary.
Association of diet and inflammation with the vaginal microbiota of pregnant individuals with or without IBD
Authors: Vargas-Robles Daniela , Yap Yan Rou , Singha Biplab , Tien Joyce , Purandare Mallika , Rojas-Correa Mayra , Madziar Camilla , Picker Mellissa , Dumont Tina , Leftwich Heidi , Frisard Christine F. , Ward Doyle V. , Peter Inga , Olendzki Barbara , Maldonado-Contreras Ana
Published: April 2024

Background and aims

Vaginal dysbiosis has been associated with adverse pregnancy outcomes. Here, we characterized the vaginal microbiota of pregnant individuals with inflammatory bowel disease (IBD) and investigated whether gut or vaginal inflammation and diet influence the vaginal microbiota diversity of these individuals.

Study Design

We recruited 48 individuals in their third trimester of pregnancy (IBD=23 and HC=18). We characterized the vaginal microbiota by16S rRNAsequencing and the gut microbiota by shotgun sequencing. We measured fecal calprotectin in stool and pro-inflammatory cytokines in vaginal fluids. We determine dietary quality using validated 24-hour dietary recalls.

Results

Pregnant individuals with IBD exhibit higher levels of fecal calprotectin and increased expression of Th17 pro-inflammatory cytokines (i.e., IL-6, IL-8, IL-17) in the vaginal mucosa compared to healthy pregnant individuals. High fecal calprotectin correlated with high vaginal microbiota diversity. Also, IL-4 (reduced in IBD) was associated with vaginal microbial composition. Regardless of IBD status, pregnant individuals with healthier diets and particularly optimal servings of vegetables and sugars exhibited a vaginal microbiota dominated byLactobacillus crispatus, a species associated with a lower risk of preterm birth and bacterial vaginosis.

Conclusion

Besides gut inflammation, pregnant individuals with IBD also exhibit a Th17 immune tone in the vaginal mucosa. The vaginal microbiota diversity or composition, particularly high in the beneficialL. crispatus,is positively associated with healthier diets, regardless of IBD status.

Why was the study conducted?

An altered vaginal microbiota has been implicated in preterm birth. There is no research on the vaginal microbiome and the factors that influence it in pregnant individuals with Inflammatory Bowel Disease (IBD) at a higher risk of preterm delivery.

Key findings

Pregnant individuals with IBD exhibit a comparable vaginal microbiome to healthy pregnant individuals. However, pregnant individuals with IBD present a vaginal immune profile characterized by increased levels of Th17 pro-inflammatory cytokines. High dietary quality, and optimal consumption of vegetables and added sugars were associated with vaginal dominance by the beneficialL. crispatus.

What does this add to what is known?

Our results indicate that the vaginal immune environment and not the microbiome might explain poor pregnancy outcomes for individuals with IBD. Moreover, our study supports the importance of diet to favorL. crispatus,a bacterium associated with a lower risk of preterm birth.
Cognitive correlates of psychopathology in Functional/Dissociative Seizures and non-lesional epilepsy: an exploratory study
Authors: Faiman Irene , Young Allan H. , Shotbolt Paul
Published: April 2024

STRUCTURED ABSTRACT

Objective

To explore the relationship between cognitive functioning and psychopathological features in Functional/Dissociative Seizures (FDS), and test whether this differs from that observed in epilepsy.

Methods

We recruited a cross-sectional sample of adults (age > 18) with a diagnosis of non-lesional epilepsy or FDS between January 2021 and July 2022. Participants completed a series of psychiatric questionnaires and neuropsychological measures. Spearman’s Correlation Coefficient was computed between each of the psychiatric and cognitive measures in each group. Fisher’s Z test of significance for independent correlation coefficients then tested the significance of the difference between correlation coefficients for the two groups.

Results

There were no group differences in neuropsychological test scores. However, people with FDS reported higher seizure severity, depression levels, number of medically unexplained somatic symptoms, and exposure to traumatic events compared to epilepsy. Results of the Fisher’s Z-test revealed significant differences in correlation coefficients between groups in two instances. First, in the association between the number of traumatic experiences and cognitive switching (z = 2.77, p = 0.006); the number of traumatic experiences were positively associated with cognitive switching in epilepsy but showed a non-significant negative trend in FDS. Secondly, in the association between vocabulary abilities and the number of medically unexplained symptoms (z = -2.71; p = 0.007); higher vocabulary ability was associated with fewer somatic symptoms in epilepsy, while no such correlation was observed in FDS.

Significance

This study provides preliminary evidence for the complex interplay between cognitive functioning and psychopathology in FDS and epilepsy. Neurocognitive functioning such as vocabulary abilities or attentional switching may play a role in the expression or maintenance of pathological features of FDS.

KEY POINTS

People with non-lesional epilepsy or Functional/Dissociative Seizures (FDS) perform more poorly than healthy controls on neuropsychological measures.

It is often thought that psychopathological factors influence cognitive presentation in FDS, but this hypothesis has received little empirical support.

This study explores the relationship between cognition and psychopathology in FDS and epilepsy.

Correlation analyses reveal distinct associations in FDS compared to epilepsy, suggesting potential differences in underlying mechanisms.

Neurocognitive processes such as vocabulary abilities or attentional switching might contribute to FDS generation or presentation.
Race, ethnicity, and risk for colonization and infection with key bacterial pathogens: a scoping review
Authors: Avendano Esther E. , Blackmon Sarah Addison , Nirmala Nanguneri , Chan Courtney W. , Morin Rebecca A. , Balaji Sweta , McNulty Lily , Argaw Samson Alemu , Doron Shira , Nadimpalli Maya L.
Published: April 2024

Background

Racial and ethnic disparities in infectious disease burden have been reported in the USA and globally, most recently for COVID-19. It remains unclear whether such disparities also exist for priority bacterial pathogens that are increasingly antimicrobial-resistant. We conducted a scoping review to summarize published studies that report on colonization or community-acquired infection with pathogens among different races and ethnicities.

Methods

We conducted an electronic literature search of MEDLINE®, Daily, Global Health, Embase, Cochrane Central, and Web of Science from inception to January 2022 for eligible observational studies. Abstracts and full-text publications were screened in duplicate for studies that reported data for race or ethnicity for at least one of the pathogens of interest.

Results

Fifty-four observational studies in 59 publications met our inclusion criteria. Studies reported results forStaphylococcus aureus(n=56),Escherichia coli(n=8), Pseudomonas aeruginosa(n=2), Enterobacterales (n=1),Enterococcus faecium(n=1), andKlebsiella pneumoniae(n=1), and were conducted in the USA (n=42), Israel (n=5), New Zealand (n=4), Australia (n=2), and Brazil (n=1). USA studies most often examined Black and Hispanic minority groups and regularly reported a higher risk of these pathogens in Black persons and mixed results for Hispanic persons. Ethnic minority groups were often reported to be at a higher risk in other countries.

Conclusion

Sufficient evidence was identified to justify systematic reviews and meta-analyses evaluating the relationship between race, ethnicity, and community-acquiredS. aureusandE. coli,although data were rare for other pathogens. We recommend that future studies clarify whether race and ethnicity data are self-reported, collect race and ethnicity data in conjunction with the social determinants of health, and make a concerted effort to include non-English speakers and Indigenous populations from the Americas, when possible.
Red flags to screen for vertebral or carotid artery dissection in patients with neck pain or headache: a scoping review protocol
Authors: Feller Daniel , de Zoete Annemarie , Maselli Filippo , Mourad Firas , Chiarotto Alessandro , Koes Bart
Published: April 2024

Background

Vertebral and carotid artery dissections may present as neck pain and/or headache in their early phases. Consequently, clinicians must screen for arterial dissections when assessing neck pain and/or headache patients. Considering that no secondary studies have been published on the red flags to screen for arterial dissections in patients with neck pain/headache, our scoping review will aim to gain a comprehensive understanding of the existing literature on patients with a carotid or vertebral artery dissection presenting with a primary complaint of neck pain and/or headache regarding the prevalence of associated signs and symptoms (e.g., neurological impairments and visual problems), the pain characteristics (e.g., intensity and localization), the demographic characteristics (e.g., gender and age), the prevalence of risk factors (e.g., cardiovascular), the mechanism of onset, and other relevant clinical predictors (e.g., comorbidities).

Methods

We will search MEDLINE (via PubMed), Embase, CINHAL, and Scopus. In addition, we will use Web of Science to implement backward and forward citation tracking strategies. We will include any primary study design (e.g., case–control studies, case reports and case series, and cohort studies) written in English, Dutch, or Italian without any time restriction. To be included, studied had to focus on adult patients (> 18 years of age) of any gender with a diagnosis of vertebral or artery dissection and with a primary complaint of neck pain and/or headache, with a reporting on other signs/symptoms, pain characteristics, demographic information, risk factors, or onset mechanisms. Two authors will independently perform the study selection and data extraction phases. Results from the scoping review will be summarized descriptively through tables and diagrams. As a scoping review, we will highlight any gaps in the existing literature regarding our research questions.
Multiclass Classification of Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder, and Typically Developed Individuals Using fMRI Functional Connectivity Analysis
Authors: Alves Caroline Lourenco , Martinelli Tiago , Sallum Loriz Francisco , Rodrigues Francisco Aparecido , Toutain Thaise G. L. de O. , Porto Joel Augusto Moura , Thielemann Christiane , Aguiar Patricia Maria de Carvalho , Moeckel Michael
Published: April 2024

Neurodevelopmental conditions, such as Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD), present unique challenges due to overlapping symptoms, making an accurate diagnosis and targeted intervention difficult. Our study employs advanced machine learning techniques to analyze functional magnetic resonance imaging (fMRI) data from individuals with ASD, ADHD, and typically developed (TD) controls, totaling 120 subjects in the study. Leveraging multiclass classification (ML) algorithms, we achieve superior accuracy in distinguishing between ASD, ADHD, and TD groups, surpassing existing benchmarks with an area under the ROC curve near 98%. Our analysis reveals distinct neural signatures associated with ASD and ADHD: individuals with ADHD exhibit altered connectivity patterns of regions involved in attention and impulse control, whereas those with ASD show disruptions in brain regions critical for social and cognitive functions. The observed connectivity patterns, on which the ML classification rests, agree with established diagnostic approaches based on clinical symptoms. Furthermore, complex network analyses highlight differences in brain network integration and segregation among the three groups. Our findings pave the way for refined, ML-enhanced diagnostics in accordance with established practices, offering a promising avenue for developing trustworthy clinical decision-support systems.