bluuebunny/crossref_metadata_2025 huggingface dataset:
Richter supraumbilical hernia managed with invagination: a case report
Authors: Dev Santosh , Luitel Prajjwol , Paudel Sujan , Devkota Shishir , Khadka Laxman , Jha Sanjeev , Dev Barsha , Neupane Nischal , Ghimire Bikal
Published: March 2024

Introduction and importance:

Richter’s hernia is an incarceration of the anti-mesenteric border of a segment of bowel through an abdominal wall defect. It primarily affects elderly individuals but can occur at any age, with a slightly increased incidence in females. The increase in laparoscopic and robotic-assisted procedures has led to a rise in Richter’s hernias.

Case presentation:

A 40-year-old male with a history of laparoscopic cholecystectomy and kidney transplantation presented with a 4-day history of supraumbilical swelling and abdominal pain. The swelling was irreducible and accompanied by mild tenderness, and local signs of inflammation were exhibited. Intraoperatively, a 1.5 cm hernia defect was found, with the sac containing omentum and a portion of bowel segment for which invagination with serosal closure with the Mayo double-breasting technique was done.

Clinical discussion:

Richter’s hernia presents with abdominal discomfort, bloating, nausea, and vomiting, with a notable feature being the delayed onset of symptoms due to its partial involvement of the bowel wall. Diagnosis can be achieved through a computed tomography (CT) scan or intraoperative exploration. Management of Richter hernia is contingent upon the patient’s clinical condition, physical examination, and suspicion of strangulation.

Conclusion:

Diagnosis of Richter’s hernia demands higher suspicion, particularly in patients with predisposing factors like a history of minimally invasive surgery. Prompt surgical intervention is crucial for reducing mortality and enhancing prognosis, with invagination alone being adequate if ischaemia is confined and mesh placement is unnecessary.
Neuromuscular Electrical Stimulation Improves Frontal Ankle Motor Control in Individuals With Chronic Ankle Instability During Drop Landing
Authors: Zheng Huifen , Tian Fei , Sun Wei , Zheng Longpo , Xiao Weihua
Published: March 2024

Objective

This study investigated the effect of neuromuscular electrical stimulation on the frontal ankle motor control in individuals with chronic ankle instability during drop landing.

Design

This was a randomized, controlled, double-blind trial. Thirty-six individuals with chronic ankle instability were randomly assigned to each group. Participants received 6-wk neuromuscular electrical stimulation intervention and sham stimulation in the neuromuscular electrical stimulation and control groups, respectively. Data were collected at week0 and week6. A mixed-effects model and analysis of covariance were employed to investigate the between-group differences in continuous and discrete outcome variables at week6, with the outcome variables at week0 as covariates.

Results

Compared to control group, neuromuscular electrical stimulation group exhibited a 2.66° (2.45, 2.86) reduction in frontal ankle inversion angle, a 47.41°/sec (−16.05, −78.77) decrease in peak ankle inversion angular velocity, and a 0.43 Nm/kg (0.18, 0.68) increase in peak ankle eversion moment during drop landing at week6.

Conclusions

Applying 6-wk neuromuscular electrical stimulation to the fibularis longus resulted in decreased ankle inversion angle and ankle inversion angular velocity and increased peak ankle eversion moment during drop landing. Consequently, neuromuscular electrical stimulation could be considered an effective modality for individuals with chronic ankle instability to enhance the frontal ankle movement patterns and overall ankle motor control.
Do HIV Care Outcomes Differ by Provider Type?
Authors: Weiser John , Tie Yunfeng , Crim Stacy M. , Riedel David J. , Shouse R. Luke , Dasgupta Sharoda
Published: March 2024

Background:

We compared HIV care outcomes by HIV provider type to inform efforts to strengthen the HIV provider workforce.

Setting:

U.S.

Methods:

We analyzed data from CDC’s Medical Monitoring Project collected during 6/2019-5/2021 from 6,323 adults receiving HIV medical care. Provider types were infectious disease physicians only (ID physicians), non-ID physicians only (non-ID physicians), nurse practitioners only (NPs), physician assistants only (PAs), and ID physicians plus NPs and/or PAs (mixed providers). We measured patient characteristics, social determinants of health (SDOH), and clinical outcomes including retention in care; antiretroviral therapy prescription; antiretroviral therapy adherence; viral suppression; gonorrhea, chlamydia, and syphilis testing; satisfaction with HIV care; and HIV provider trust.

Results:

Compared with patients of ID physicians, higher percentages of patients of other provider types had characteristics and SDOH associated with poor health outcomes and received HIV care at Ryan White HIV/AIDS Program-funded facilities. After accounting for these differences, most outcomes were not meaningfully different, however higher percentages of patients of non-ID physicians, NPs, and mixed providers were retained in care (6.5, 5.6, and 12.7 percentage points, respectively) and had STI testing in the past 12 months, if sexually active (6.9, 7.4, and 13.5 percentage points, respectively).

Conclusion:

Most HIV outcomes were equivalent across provider types. However, patients of non-ID physicians, NPs, and mixed providers were more likely to be retained in care and have recommended STI testing. Increasing delivery of comprehensive primary care by ID physicians and including primary care providers in ID practices could improve HIV primary care outcomes.
68Ga-FAPI-04 PET/CT for the Evaluation of Cholangiocarcinoma
Authors: Zhang Zeyu , Cheng Chao , Jiang Hui , Pan Guixia , Yu Yong , Jin Gang , Zuo Changjing
Published: March 2024

Purpose

In this study, we evaluated and compared the diagnostic performances of 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT for primary and metastatic cholangiocarcinoma (CCA) lesions. We also investigated the performance of PET/MR for visualizing and characterizing CCA and liver metastasis lesions.

Patients and Methods

Forty-four patients with suspected CCA were recruited and underwent 68Ga-FAPI-04 and 18F-FDG PET/CT within 1 week, including 30 patients who underwent simultaneous abdominal 68Ga-FAPI-04 PET/MR scanning. The findings were confirmed by histopathology or radiographic follow-up.

Results

Compared with 18F-FDG PET/CT, 68Ga-FAPI-04 PET/CT showed higher sensitivity (94.3% vs 88.6%) and the same accuracy (86.4% vs 86.4%) in evaluating primary tumors. However, its specificity was lower (55.6% vs 77.8%). 68Ga-FAPI-04 PET was superior to 18F-FDG PET in both patient-based and lesion-based evaluations except for metastatic lesions in the liver and bone. For intrahepatic CCA, 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT (100% vs 100%) had similar detection rates, with similar uptake levels between tracers (P > 0.05). However, for extrahepatic CCA, 68Ga-FAPI-04 PET/CT had a higher detection rate (89.5% vs 78.9%), and 68Ga-FAPI-04 had a higher uptake (P < 0.05). PET/MR was more effective than PET/CT in terms of lesion conspicuity and diagnostic confidence for primary tumors and liver metastases. In addition, multisequence MRI identified more liver metastases than 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT.

Conclusions

Compared with 18F-FDG PET/CT, 68Ga-FAPI-04 PET/CT showed a higher sensitivity in detecting primary CCA tumors, involved lymph nodes, and peritoneal metastases. Compared with 68Ga-FAPI-04 PET/CT, PET/MR detected primary and liver metastatic lesions more accurately. For extrahepatic CCA, the combination of 68Ga-FAPI-04 PET/CT and abdominal PET/MRI may replace 18F-FDG PET/CT.
Additional Findings of 18F-AIF-FAPI-42 PET/CT in a Patient With Mycosis Fungoides–Type Cutaneous T-Cell Lymphoma
Authors: Liu Guanghui , Li Yaming , Du Bulin , Cui Yan , Li Xuena
Published: March 2024

A 44-year-old woman presented with extensive skin patches and pruritus persisting for 3 years. Histopathological examination of the skin from the right abdomen confirmed mycosis fungoides–type cutaneous T-cell lymphoma. Staging PET with 18F-FDG PET/CT) showed increased uptake in the skin on the right abdomen and left hip. Subsequently 18F-FAPI-42 PET/CT revealed additional foci of abnormal uptake on the skin of the chest and back.
Widespread Reactive Lymphatic and Splenic FDG Avidity After mRNA COVID Vaccination
Authors: Kavanaugh Michael , Shah Hina J.
Published: March 2024

A 75-year-old woman with history of metastatic lung adenocarcinoma in remission develops new widespread FDG-avid lymphadenopathy in the neck, chest, abdomen, and pelvis on surveillance PET/CT, as well as intense FDG uptake in the spleen, without evidence of local recurrence. Short-term follow-up PET demonstrates near-complete resolution of FDG-avid lymphatic and splenic FDG avidity without interval change in management. Further history reveals that the patient received her fifth dose of COVID mRNA vaccine 6 days before the abnormal PET. Although unilateral axillary adenopathy after COVID vaccination is well-recognized, this widespread symmetric lymphatic and splenic FDG avidity is a significantly rarer phenomenon.
Disparities Research for Pelvic Floor Disorders: A Systematic Review and Critique of Literature
Authors: Mou Tsung , Shinnick Julia , DeAndrade Samantha , Roselli Nicole , Andebrhan Sarah , Akanbi Tracey , Ackenbom Mary , Carter-Brooks Charelle , Beestrum Molly , Cichowski Sara , Brown Oluwateniola
Published: March 2024

Importance

Understanding the status of pelvic floor disorder (PFD) disparities research will allow the opportunity to advance future pelvic floor equity efforts.

Objectives

The aims of the study were to (1) characterize the landscape of PFD disparities literature using the 3 phases of disparities research framework, (2) describe the characteristics of PFD disparities studies, and (3) identify critical knowledge gaps.

Study Design

We performed a systematic review of peer-reviewed publications addressing disparities in PFDs among U.S. populations from PubMed, Embase, Scopus, or the Cochrane Database indexed between 1997 and 2022. Using the triphasic framework for advancing health disparities research by Kilbourne et al (Am J Public Health. 2006;96(12):2113–21), we categorized the included studies into the detecting phase (identifies and measures disparities in historically marginalized populations), understanding phase (establishes disparity determinants), or reducing phase (conducts interventions to alleviate inequities). All screening, coding, and quality reviews were independently performed by at least 2 authors. We used descriptive analysis and the χ2 test for comparisons.

Results

The initial search identified 10,178 studies, of which 123 were included. Of the included studies, 98 (79.7%), 22 (17.9%), and 3 (2.4%) studies were detecting, understanding, and reducing phase research, respectively. The most common disparity category investigated was race and ethnicity (104 studies), and one third of these studies attributed drivers of racial and ethnic differences to structural influences. Publications of detecting phase studies outpaced the growth of understanding and reducing phase research.

Conclusions

Most PFD disparities research focused on identifying historically marginalized populations with inadequate progression to understanding and reducing phases. We recommend progressing PFD disparities research beyond the detecting phase to advance health equity in PFD care.
Parasomnia induced by lemborexant: a case report
Authors: Nakamura Toshinori , Arai Yusuke , Hagiwara Tetsuya , Kitoh Ryosuke , Sasayama Daimei , Washizuka Shinsuke
Published: March 2024

Lemborexant, an orexin receptor antagonist, is effective not only for sleep disorders but also for preventing and treating delirium. To date, no complex sleep-related behaviors due to lemborexant have been reported. Herein, we present the case of a 69-year-old male patient who was hospitalized for oral floor and tongue cancer and developed delirium after surgery; however, upon lemborexant dosage increase, used to treat insomnia, he developed abnormal nocturnal behavior. This symptom rapidly improved when lemborexant was discontinued. Distinguishing parasomnia from delirium is important because the treatment of these two conditions differs. Although rapid eye movement sleep behavior or sleepwalking was the cause of this parasomnia, a definitive diagnosis could not be established. If qualitatively distinct abnormal behavior is observed compared to delirium after increasing lemborexant dosage, the possibility of parasomnia should be considered.
Modelling Glioma Stem Cell-mediated Tumorigenesis Using Zebrafish PDX Systems
Authors: Mahendran Hema Priya , Cieslukowski Alan , Lubanska Dorota , Philbin Nicholas , Stringer Keith Franklin , Habashy Philip , Stover Mat , deCarvalho Ana C. , Soliman Mohamed , Shamisa Abdalla , Porter Lisa
Published: March 2024

Glioblastoma is an aggressive brain tumour associated with high post-therapy recurrence and very poor survival rates. One of the factors contributing to the aggressive nature of this disease is the level of heterogeneity seen at the phenotypic and genetic level. Glioma Stem Cells (GSCs) are stem-like cells within the tumour with the ability to self-renew and give rise to different types of cells within the tumour, hence giving rise to the heterogeneity found in glioblastoma. GSCs are often implicated in the resistance of glioma to standard of care radiation and chemotherapy. The physical niche within a tumour mass supports stemness and aggressive characteristics of GSCs, hence, experimental systems providing a relevant tumour microenvironment are critical for adequate assessment of molecular mechanisms regulating GSC populations. Although, mouse models are a staple of anin vivoexperimental design, they are neither time-nor cost-efficient.Danio rerio(zebrafish) patient-derived xenografts (PDXs) overcome several of the obstacles of the mammalian systems. Zebrafish constitute a high throughput, easily reproducible experimental platform allowing for life relevant investigation into the aggressiveness of GSC populations. This chapter describes methods required for generation of zebrafish PDXs to study aspects of GSC-mediated tumorigenesis and interactions with the tumour microenvironment. Consistency between labs for these experiments is required to move the discovery of effective treatments for glioblastoma moving forward.
Histology-guided mathematical model of tumor oxygenation: sensitivity analysis of physical and computational parameters
Authors: Ojwang’ Awino Maureiq E. , Bazargan Sarah , Johnson Joseph O. , Pilon-Thomas Shari , Rejniak Katarzyna A.
Published: March 2024

A hybrid off-lattice agent-based model has been developed to reconstruct the tumor tissue oxygenation landscape based on histology images and simulated interactions between vasculature and cells with microenvironment metabolites. Here, we performed a robustness sensitivity analysis of that model’s physical and computational parameters. We found that changes in the domain boundary conditions, the initial conditions, and the Michaelis constant are negligible and, thus, do not affect the model outputs. The model is also not sensitive to small perturbations of the vascular influx or the maximum consumption rate of oxygen. However, the model is sensitive to large perturbations of these parameters and changes in the tissue boundary condition, emphasizing an imperative aim to measure these parameters experimentally.
Obstacle Negotiation in Female Locust Oviposition Digging
Authors: Klechevski Chen , Kats Lazar , Ayali Amir
Published: March 2024

The female locust lays its eggs deep within soft substrate to protect them from predators and provide optimal conditions for successful hatching. During oviposition digging, the female’s abdomen extends into the ground, guided by a dedicated excavation mechanism at its tip, comprising two pairs of specialized digging valves. Little is known about how these active valves negotiate the various obstacles encountered on their path. In this study, female locusts oviposited their eggs in specialized sand-filled tubes with pre-inserted 3D-printed plastic obstacles. The subterranean route taken by the abdomen and digging valves upon encountering the obstacles was investigated, characterized, and compared to that in control tubes without obstacles. Data were obtained by way of visual inspection, by utilizing Cone Beam Computed Tomography scans in high-definition mode, and by making paraffin casts of the oviposition burrows (after egg hatching). We demonstrate, for the first time, the subterranean navigation ability of the female locust’s excavation mechanism and its ability to circumvent obstacles during oviposition. Finally, we discuss the role of active sensory-motor mechanisms versus the passive embodied function of the valves, central control, and decision-making.
Dynamic energy budget model for a bumble bee colony: Predicting the spatial distribution and dynamics of colonies across multiple seasons
Authors: Capera-Aragones Pau , Mariño Joany , Hurford Amy , Tyson Rebecca C. , Foxall Eric
Published: March 2024

Bumble bees are important pollinators of many crops around the world. In recent decades, agricultural intensification has resulted in significant declines in bumble bee populations and the pollination services they provide. Empirical studies have shown that this trend can be reversed, however, by enhancing the agricultural landscape with natural habitat, such as adding wildflower patches adjacent to crops. Despite the empirical evidence, the mechanisms behind these positive effects are not fully understood, and the specific characteristics of the enhanced natural habitat that would maximize benefits are unclear at this time. Theoretical studies, in the form of mathematical models, have proven useful in elucidating the underlying mechanisms and determining the optimal natural habitat configurations. Existing models, however, generally focus only on particular aspects of bumble bee behaviour; some models are accurate at describing population dynamics, while others are accurate at describing their spatial distribution. In this work, we build a unique model coupling population dynamics, using a whole-colony Dynamic Energy Budget (DEB) approach, to a spatial distribution model based on the maximum energy principle. This coupling gives valuable new insights into the effects of spatial arrangements on population dynamics, and vice-versa. With our model, we answer questions such as when, how much, or what type of wildflower patches should be planted to maximize crop pollination services and minimize bee decline. We find that planting wildflowers that bloom before and after crop bloom is crucial to achieve high pollination services and preserving wild pollinator populations. We also find that small quantities of natural habitat are needed when the crop is nutritionally rich, but higher quantities are most beneficial when the crop is nutritionally deficient.
Uncalled4 improves nanopore DNA and RNA modification detection via fast and accurate signal alignment
Authors: Kovaka Sam , Hook Paul W. , Jenike Katharine M. , Shivakumar Vikram , Morina Luke B. , Razaghi Roham , Timp Winston , Schatz Michael C.
Published: March 2024

Nanopore signal analysis enables detection of nucleotide modifications from native DNA and RNA sequencing, providing both accurate genetic/transcriptomic and epigenetic information without additional library preparation. Presently, only a limited set of modifications can be directly basecalled (e.g. 5-methylcytosine), while most others require exploratory methods that often begin with alignment of nanopore signal to a nucleotide reference. We present Uncalled4, a toolkit for nanopore signal alignment, analysis, and visualization. Uncalled4 features an efficient banded signal alignment algorithm, BAM signal alignment file format, statistics for comparing signal alignment methods, and a reproduciblede novotraining method for k-mer-based pore models, revealing potential errors in ONT’s state-of-the-art DNA model. We apply Uncalled4 to RNA 6-methyladenine (m6A) detection in seven human cell lines, identifying 26% more modifications than Nanopolish using m6Anet, including in several genes where m6A has known implications in cancer. Uncalled4 is available open-source atgithub.com/skovaka/uncalled4.
Lipid Peroxidation and Type I Interferon Coupling Fuels Pathogenic Macrophage Activation Causing Tuberculosis Susceptibility
Authors: Yabaji Shivraj M. , Zhernovkov Vadim , Araveti Prasanna Babu , Lata Suruchi , Rukhlenko Oleksii S. , Abdullatif Salam Al , Vanvalkenburg Arthur , Alekseev Yuriy , Ma Qicheng , Dayama Gargi , Lau Nelson C. , Johnson W. Evan , Bishai William R. , Crossland Nicholas A. , Campbell Joshua D. , Kholodenko Boris N. , Gimelbrant Alexander A. , Kobzik Lester , Kramnik Igor
Published: March 2024

A quarter of human population is infected with Mycobacterium tuberculosis, but less than 10% of those infected develop pulmonary TB. We developed a genetically defined sst1-susceptible mouse model that uniquely reproduces a defining feature of human TB: the development of necrotic lung granulomas and determined that the sst1-susceptible phenotype was driven by the aberrant macrophage activation. This study demonstrates that the aberrant response of the sst1-susceptible macrophages to prolonged stimulation with TNF is primarily driven by conflicting Myc and antioxidant response pathways leading to a coordinated failure 1) to properly sequester intracellular iron and 2) to activate ferroptosis inhibitor enzymes. Consequently, iron-mediated lipid peroxidation fueled IFNβ superinduction and sustained the Type I Interferon (IFN-I) pathway hyperactivity that locked the sst1-susceptible macrophages in a state of unresolving stress and compromised their resistance to Mtb. The accumulation of the aberrantly activated, stressed, macrophages within granuloma microenvironment led to the local failure of anti-tuberculosis immunity and tissue necrosis. The upregulation of Myc pathway in peripheral blood cells of human TB patients was significantly associated with poor outcomes of TB treatment. Thus, Myc dysregulation in activated macrophages results in an aberrant macrophage activation and represents a novel target for host-directed TB therapies.
Analysis and visualization of quantitative proteomics data using FragPipe-Analyst
Authors: Hsiao Yi , Zhang Haijian , Li Ginny Xiaohe , Deng Yamei , Yu Fengchao , Kahrood Hossein Valipour , Steele Joel R. , Schittenhelm Ralf B. , Nesvizhskii Alexey I.
Published: March 2024

The FragPipe computational proteomics platform is gaining widespread popularity among the proteomics research community because of its fast processing speed and user-friendly graphical interface. Although FragPipe produces well-formatted output tables that are ready for analysis, there is still a need for an easy-to-use and user-friendly downstream statistical analysis and visualization tool. FragPipe-Analyst addresses this need by providing an R shiny web server to assist FragPipe users in conducting downstream analyses of the resulting quantitative proteomics data. It supports major quantification workflows including label-free quantification, tandem mass tags, and data-independent acquisition. FragPipe-Analyst offers a range of useful functionalities, such as various missing value imputation options, data quality control, unsupervised clustering, differential expression (DE) analysis using Limma, and gene ontology and pathway enrichment analysis using Enrichr. To support advanced analysis and customized visualizations, we also developed FragPipeAnalystR, an R package encompassing all FragPipe-Analyst functionalities that is extended to support site-specific analysis of post-translational modifications (PTMs). FragPipe-Analyst and FragPipeAnalystR are both open-source and freely available.
A new group of LysM-RLKs involved in symbiotic signal perception and arbuscular mycorrhiza establishment
Authors: Ding Yi , Gasciolli Virginie , Medioni Lauréna , Gaston Mégane , de-Regibus Annélie , Rem-blière Céline , Bono Jean Jacques , Cullimore Julie , Dalmais Marion , Saffray Christine , Mazeau Solène , Bendahmane Abdelhafid , Sibout Richard , Vandenbussche Michiel , Rouster Jacques , Wang Tongming , He Guanghua , Masselin Arnaud , Cottaz Sylvain , Fort Sébastien , Lefebvre Benoit
Published: March 2024

Lipo-chitooligosaccharides (LCO) and short-chain chitooligosaccharides (CO) are produced by arbuscular mycorrhizal fungi (AMF) and activate the plant symbiosis signalling pathway, which is essential for mycorrhiza formation. High affinity LCO receptors belonging to the LysM receptor-like kinase (LysM-RLK) phylogenetic groupLYR-IAplay a role in AM establishment, but no plant high affinity short-chain CO receptors have yet been identified. Here we studied members of the uncharacterizedLYR-IBgroup, and found that they show high affinity for LCO, short- and long-chain CO, and play a complementary role with theLYR-IALCO receptors for AM establishment. WhileLYR-IBknock out mutants had a reduced AMF colonization in several species, constitutive/ectopic expression in wheat increased AMF colonization.LYR-IBfunction is conserved in all tested angiosperms, but in most japonica rice a deletion creates a frameshift in the gene, explaining differences in AM phenotypes between rice and other monocot singleLYR-IAmutants. In conclusion, we identified a class of LysM-RLK receptors in angiosperms with new biochemical properties and a role in both LCO and CO perception for AM establishment.
XopM, a FFAT motif containing type-III effector protein fromXanthomonas, suppresses PTI responses at the plant plasma membrane
Authors: Brinkmann Charlotte , Bortlik Jennifer , Raffeiner Margot , Üstün Suayib , Börnke Frederik
Published: March 2024

Many Gram-negative pathogenic bacteria use type-III effector proteins (T3Es) as essential virulence factors to suppress host immunity and to cause disease. However, in many cases the molecular function of T3Es remains unknown. The plant pathogenXanthomonas campestrispv.vesicatoria(Xcv) is the causal agent of bacterial spot disease on tomato and pepper plants and is known to translocate around 30 T3Es into its host cell, which collectively suppress plant defense and promote infection. XopM is anXcvcore T3E with unknown function that has no similarity to any other known protein. We found that XopM interacts with vesicle-associated membrane protein (VAMP)-associated proteins (VAPs) in an isoform specific manner. The endoplasmic reticulum (ER) integral membrane protein VAP is a common component of membrane contact sites involved in both tethering and lipid transfer by binding directly to proteins containing a FFAT [two phenylalanines (FF) in an acidic tract (AT)] motif. Sequence analyses revealed that XopM displays two FFAT motifs that cooperatively mediated the interaction of XopM with VAP. When expressed in plants, XopM supports growth of a non-pathogenic bacterial strain and dampens the production of reactive oxygen species, indicating its ability to suppress plant immunity. Further analyses revealed that the interaction with VAP and the ability to suppress PTI are structurally and functionally separable. Although XopM requires localization to the host membrane system for full PTI suppression activity. We discuss a working model in which XopM uses FFAT-motifs to target the membrane in order to interfere with early PTI responses.
A six molecule nenonatal serum metabolite biosignature has high neonatal sepsis predictability and resolves upon treatment completion
Authors: Ahmed Riya , Behera Anil , Sarangi Adyasha , Debata Pradeep , Gaind Rajni , Kaushal GP , Gur Renu , Shrivastava Sushil , Nirmal Kirti , Kaur Ravinder , Nangia Sushma , Kumar Vivek , Sankar M Jeeva , Nanda Ranjan Kumar
Published: March 2024

Background

Sepsis, a life-threatening disorder with multi-organ dysfunction, is a leading cause of neonatal mortality. Current microbiology-based sepsis diagnosis is time-consuming, and identification of deregulated host serum metabolite signatures might be useful to develop early screening tools and host-directed therapeutics.

Methods

In this multi-institutional study, 500 neonates (41.2% female) were classified to culture-positive (CP) or negative sepsis (CN) cases and controls (no sepsis: NS, healthy control: HC) based on their microbial culture and mass spectrometry test results. The neonates were randomly grouped into two discovery sets (I:n=71; II:n=269), a validation set (n=60), and a longitudinally followed-up population (n=100). Serum samples of these neonates were processed and profiled using gas chromatography coupled to either quadrupole or time-of-flight mass spectrometry (GC-MS/-TOF-MS). Deregulated (log2case/control ≥±0.58, p<0.05) serum metabolites in sepsis cases were identified from the discovery sets and their predictive accuracy in the validation set was calculated using area under the receiving operator characteristic curve (AUC of ROC). The abundance of these deregulated metabolites was monitored in the longitudinally followed-up neonates (CP:n=29, CN:n=35, and NS:n=36) completing therapeutic intervention.

Results

Most of the CP cases wereKlebsiella pneumoniae(28.6%) orAcinetobacter baumannii(20.6%) positive. Gestational age (CP: 30.9±1.9 weeks, CN: 30.9±1.8 weeks, HC: 32.3±1.3 weeks, NS: 31.6±1.5 weeks) and birthweight (CP: 1.4±0.3 kg, CN: 1.4±0.4 kg, HC: 1.7±0.3 kg, NS: 1.6±0.3 kg) were lower in sepsis neonates compared to controls. Out of 57 identified serum metabolites, a set of six (1,5-Anhydro-D-sorbitol-Lactic-acid-Malic-acid-Myo-inositol-Phenylalanine-Lysine) were identified as sepsis biosignature. The AUC of ROC of the biosignature to predict CP or CN from HC was 0.97 and from NS was 0.84 and 0.64, respectively. Myo-inositol, malic acid, and 1,5-anhydro-D-sorbitol revert to the HC levels in neonates completing therapeutic intervention.

Conclusions

A serum metabolite signature showed a >97% predictive accuracy for sepsis and could be further explored for its diagnostic and host-directed therapeutic potential.
Applicability of AlphaFold2 in the modeling of dimeric, trimeric, and tetrameric coiled-coil domains
Authors: Madaj Rafal , Martinez-Goikoetxea Mikel , Kaminski Kamil , Ludwiczak Jan , Dunin-Horkawicz Stanislaw
Published: March 2024

Coiled coils are a common protein structural motif involved in cellular functions ranging from mediating protein-protein interactions to facilitating processes such as signal transduction or regulation of gene expression. They are formed by two or more alpha helices that wind around a central axis to form a buried hydrophobic core. Various forms of coiled-coil bundles have been reported, each characterized by the number, orientation, and degree of winding of the constituent helices. This variability is underpinned by short sequence repeats that form coiled coils and whose properties determine both their overall topology and the local geometry of the hydrophobic core. The strikingly repetitive sequence has enabled the development of accurate sequence-based coiled-coil prediction methods; however, the modeling of coiled-coil domains remains a challenging task. In this work, we evaluated the accuracy of AlphaFold2 in modeling coiled-coil domains, both in modeling local geometry and in predicting global topological properties. Furthermore, we show that the prediction of the oligomeric state of coiled-coil bundles can be achieved by using the internal representations of AlphaFold2, with a performance better than any previous state-of-the-art method (code available athttps://github.com/labstructbioinf/dc2_oligo).
Breaking the rule: An exceptional Y chromosome introgression between deeply divergent primate species
Authors: Jensen Axel , Horton Emma R. , Amboko Junior , Parke Stacy-Anne , Hart John A. , Tosi Anthony , Guschanski Katerina , Detwiler Kate M.
Published: March 2024

Hybridization between distinct lineages is widespread in nature, with important implications for adaptation and speciation. If hybrids are fertile, alleles can introgress across species boundaries. Hybrid fitness is often sex dependent, with heterogametic hybrids showing lower fitness than homogametic individuals, a phenomenon known as Haldane’s rule. Consequently, loci inherited strictly through the heterogametic sex rarely introgress. We focus on the Y-chromosomal history of guenons (tribe Cercopithecini), a group of African primates that hybridized extensively throughout their evolutionary history. Although our inferences suggest that Haldane’s rule is generally in place, we uncover a remarkable Y chromosome introgression event fromCercopithecus mitisintoC. denti, which occurred ca. six million years after their initial divergence. Only a weak signal of autosomal gene flow is present, suggesting that the introgressing Y chromosome reached fixation inC. dentifrom a very low initial frequency. We use simulations to explore the evolutionary mechanisms at play, and find that selection is needed to achieve fixation of the novel Y chromosome. We identify a number of fixed protein differences between the introgressed and ancestral Y, with meiotic drive being an alternative mechanism to adaptive introgression. Our results show that the ability to produce viable and fertile heterogametic hybrids persisted for six million years in guenons, providing a remarkable exception to Haldane’s rule.
Comparing Automated Subcortical Volume Estimation Methods; Amygdala Volumes Estimated by FSL and FreeSurfer Have Poor Consistency
Authors: Sadil Patrick , Lindquist Martin A
Published: March 2024

Subcortical volumes are a promising source of biomarkers and features in biosignatures, and automated methods facilitate extracting them in large, phenotypically rich datasets. However, while extensive research has verified that the automated methods produce volumes that are similar to those generated by expert annotation, the consistency of methods with each other is understudied. Using data from the UK Biobank, we compare the estimates of subcortical volumes produced by two popular software suites: FSL and FreeSurfer. Although most subcortical volumes exhibit good to excellent consistency across the methods, the tools produce diverging estimates of amygdalar volume. Through simulation, we show that this poor consistency can lead to conflicting results, where one but not the other tool suggests statistical significance, or where both tools suggest a significant relationship but in opposite directions. Considering these issues, we discuss several ways in which care should be taken when reporting on relationships involving amygdalar volume.
Normative models combining fetal and postnatal MRI data to characterize neurodevelopmental trajectories during the transition from in- to ex-utero
Authors: Mihailov A. , Pron A. , Lefèvre J. , Deruelle C. , Desnous B. , Bretelle F. , Manchon A. , Milh M. , Rousseau F. , Auzias G. , Girard N.
Published: March 2024

The perinatal period involves transitioning from an intra- to an extrauterine environment, which requires a complex adaptation of the brain. This period is marked with dynamic and multifaceted cortical changes in both structure and function. Most studies to date have focused either on the fetal or postnatal period, independently. To the best of our knowledge, this is the first neurodevelopmental study targeting the cortical trajectory of typically developing perinatal subjects, combining MRIs from both fetal and postnatal participants. Prior to analysis, preprocessing and segmentation parameters were harmonized across all subjects in order to overcome methodological limitations that arise when studying such different populations. We conducted a normative modeling analysis on a sample of 607 subjects, age ranged 24 to 45 weeks post-conception, to observe changes that arise as participants traverse the birth barrier. We observed that the trajectories of global surface area and several volumetric features, including total gray matter, white matter, brainstem, cerebellum and hippocampi, follow distinct but continuous patterns during this transition. We further report three features presenting a discontinuity in their neurodevelopmental trajectories as participants traverse from a fetal to a postnatal environment: the extra-cerebrospinal fluid volume, the ventricular volume and global gyrification. The current study demonstrates the presence of unique neurodevelopmental patterns for several structural features during the perinatal period, and confirms that not all features are affected in the same way as they cross the birth barrier.

SIGNIFICANCE STATEMENT

The perinatal phase comprises the fetal and immediate postnatal period, and is generally described as the time surrounding birth. Comprehensively understanding this period is crucial due to the presence of dynamic and multifaceted brain changes. What makes this investigation unique is that it is the first neurodevelopmental study, to the best of our knowledge, focused on the cortical trajectory of typically developing perinatal subjects through the combination of both fetal and postnatal participants into one analysis. We report that certain brain feature trajectories change drastically as fetuses become newborns, while other features remain continuous. These observations are relevant in both the isolation of biomarkers for later cognitive and physiological disorders and in the understanding of typical cerebral development.
UrbanCepaea nemoralissnails are less likely to have nematodes trapped within their shells
Authors: Dahirel Maxime , Reyné Hannah , De Wolf Katrien , Bonte Dries
Published: March 2024

Urbanization is a major human-induced environmental change which can impact not only individual species, but also the way these species interact with each other. As a group, terrestrial molluscs interact frequently with a wide diversity of parasites, yet the way these interactions vary across space and in response to environmental pressures is poorly documented. In this study we leveraged a recently discovered defence mechanism, by which snails trap parasitic nematodes in their shells, to explore how snail-nematodes interactions may vary in response to city life. We examined shells from the generalist snailCepaea nemoralissampled in three urban areas in Belgium for trapped nematodes, and attempted to link this to urbanization and shell phenotypic traits. We found that even a small degree of urbanization led to large decreases in the rates of shell encapsulation, and that larger snails were more likely to contain trapped nematodes. However, we found no evidence that shell colour, which had been previously linked to immune function, was correlated to encapsulation rates. We discuss how between-population variation in encapsulation rates can result from urbanization-induced changes on the nematodes side, the snail side, or both, and suggest potential tests for future studies aiming to disentangle these mechanisms.
Role of the right middle occipital gyrus in egocentric spatial orientation in reference to gravitational information: Evidence from a pre-registered rTMS study
Authors: Tani Keisuke , Naito Eiichi , Mizobe Koji , Hirose Satoshi
Published: March 2024

Accurate perception of the orientation of external objects relative to the body, known asegocentric spatial orientation, is fundamental to action. Previously, we found via behavioral and magnetic resonance imaging voxel-based morphometry studies that egocentric spatial orientation is distorted when the whole body is tilted with respect to gravity, and that the magnitude of this perceptual distortion is correlated with grey matter volume in the right middle occipital gyrus (rMOG). In the present pre-registered study, we demonstrated that neural processing in the rMOG is indeed a cause of the perceptual distortion. We transiently suppressed neural activity in the rMOG by applying low-frequency repetitive transcranial magnetic stimulation (rTMS) and evaluated the consequent effect on perceptual distortion. Our results showed that while rTMS over the rMOG significantly reduced perceptual distortion when the body was tilted with respect to gravity, it did not affect egocentric spatial orientation when in the upright position. No changes in perceptual distortion were observed when rTMS was applied to a control site (right temporoparietal junction) or to air (sham TMS). These results indicate that neural processing in the rMOG during body tilt is an essential cause of perceptual distortion, suggesting that the rMOG is engaged in egocentric spatial orientation concerning gravitational information.

Significance statement

The findings of this pre-registered study support a causal role of neural activity in the right middle occipital gyrus (rMOG) in the perceptual distortion of egocentric spatial orientation induced by whole-body tilt relative to gravity. We suppressed neural activity in the rMOG using low-frequency repetitive transcranial magnetic stimulation (rTMS) and measured perceptual distortion. We observed a significant reduction in perceptual distortion after rTMS over the rMOG, but not after control or sham rTMS. These results provide, for the first time, direct evidence of the engagement of the rMOG in egocentric spatial orientation in reference to gravitational information.
Cognitive modeling of the Mnemonic Similarity Task as a digital biomarker for Alzheimer’s Disease
Authors: Vanderlip Casey , Lee Michael D. , Stark Craig E.L.
Published: March 2024

AD related pathologies, such as beta-amyloid (Aβ) and phosphorylated tau (pTau), are evident decades before any noticeable decline in memory occurs. Identifying individuals during this asymptomatic phase is crucial for timely intervention. The Mnemonic Similarity Task (MST), a modified recognition memory task, is especially relevant for early AD screening, as it assesses hippocampal integrity, a region affected (both directly and indirectly) early in the progression of the disease. Further, strong inferences on the underlying cognitive mechanisms that support performance on this task can be made using Bayesian cognitive modeling. We assessed whether analyzing MST performance using a cognitive model could detect subtle changes in cognitive function and AD biomarker status prior to overt cognitive decline. We analyzed MST data from >200 individuals (young, cognitively healthy older adults, and individuals with MCI), a subset of which also had existing CSF Aβ and pTau data. Traditional performance scores and cognitive modeling using multinomial processing trees was applied to each participants MST data using Bayesian approaches. We assessed how well each could predict age group, memory ability, MCI status, Aβ/pTau status using ROC analyses. Both approaches predicted age group membership equally, but cognitive modeling approaches exceeded traditional metrics in all other comparisons. This work establishes that cognitive modeling of the MST can detect individuals with AD prior to cognitive decline, making it a potentially useful tool for both screening and monitoring older adults during the asymptomatic phase of AD.
Planning and adjusting the COVID-19 booster vaccination campaign to reduce disease burden
Authors: Domenico Laura Di , Goldberg Yair , Colizza Vittoria
Published: March 2024

As public health policies shifted in 2023 from emergency response to long-term COVID-19 disease management, immunization programs started to face the challenge of formulating routine booster campaigns in a still highly uncertain seasonal behavior of the COVID-19 epidemic. Mathematical models assessing past booster campaigns and integrating knowledge on waning of immunity can help better inform current and future vaccination programs. Focusing on the first booster campaign in the 2021/2022 winter in France, we used a multi-strain age-stratified transmission model to assess the effectiveness of the observed booster vaccination in controlling the succession of Delta, Omicron BA.1 and BA.2 waves. We explored counterfactual scenarios altering the eligibility criteria and inter-dose delay. Our study showed that the success of the immunization program in curtailing the Omicron BA.1 and BA.2 waves was largely dependent on the inclusion of adults among the eligible groups, and was highly sensitive to the inter-dose delay, which was changed over time. Shortening or prolonging this delay, even by only one month, would have required substantial social distancing interventions to curtail the hospitalization peak. Also, the time window for adjusting the delay was very short. Our findings highlight the importance of readiness and adaptation in the formulation of routine booster campaign in the current level of epidemiological uncertainty.
Brief psychological interventions to improve mental health outcomes in refugee populations: A systematic review
Authors: Daniel Nadia A. , Liu Xin , Thomas Elizabeth T. , Eraneva-Dibb Emily , Ahmad Al-Maz , Heneghan Carl
Published: March 2024

Background

Refugees, asylum seekers, and internally displaced people experience a high burden of mental health problems owing to their experiencing traumas and stressful events.

Objective

To summarise the available evidence and analyse the efficacy of brief psychological interventions (< 3 months) on improving mental health outcomes, including depression, anxiety, and post-traumatic stress disorder (PTSD)-related symptoms in refugees.

Method

We searched Medline, EMBASE, PsycINFO, CINAHL, and Global Index Medicus from inception to 19 December 2023. We included controlled studies using any cognitive behavioural therapy (CBT) or CBT-based therapies delivered over a short time (< 3 months), which reported mental health outcomes pre-and post-intervention. We conducted meta-analyses using random effects to derive pooled summary statistics.

Results

34 eligible studies across 36 publications were retrieved for analysis, and 33 studies were included in the meta-analysis. There was an overall improvement in immediate mental health outcomes for all three domains, with analysis of 13 studies on anxiety outcomes (SMD −1.12, 95% CI −1.72 to −0.52), 20 studies on depression (SMD −1.04, 95% CI −1.97 to −0.11), and 24 studies on PTSD (SMD −0.82, 95% CI −1.20 to −0.45). At 3 to 6-month follow-up, however, analysis of mental health outcomes shows no significant change from baseline, with standard mean differences of 0.24 (95% CI −0.94 to 1.42) across 4 studies, −0.73 (95% CI −2.14 to 0.68) across 9 studies, and 0.29 (95% CI −0.94 to 1.53) across 12 studies for anxiety, depression, and PTSD respectively.

Conclusion

Low-level evidence shows brief psychological interventions positively affect refugees and internally displaced people’s mental well-being. Heterogeneity was high, even among subgroups, impacting our findings’ generalisability.

HIGHLIGHTS

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We analysed the evidence on the use of brief CBT-based psychological interventions to improve mental health outcomes in forcibly displaced persons.

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These interventions had a positive effect on anxiety, depression, and PTSD, though there was high heterogeneity between studies.

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Positive effects on mental health disappeared at long-term follow-up.