bluuebunny/crossref_metadata_2025 huggingface dataset:
“What Else Could It Be?” A Scoping Review of Questions for Patients to Ask Throughout the Diagnostic Process
Authors: Hill Mary A. , Coppinger Tess , Sedig Kimia , Gallagher William J. , Baker Kelley M. , Haskell Helen , Miller Kristen E. , Smith Kelly M.
Published: September 2024

Background

Diagnostic errors are a global patient safety challenge. Over 75% of diagnostic errors in ambulatory care result from breakdowns in patient-clinician communication. Encouraging patients to speak up and ask questions has been recommended as one strategy to mitigate these failures.

Objectives

The goal of the scoping review was to identify, summarize, and thematically map questions patients are recommended to ask during ambulatory encounters along the diagnostic process. This is the first step in a larger study to co-design a patient-facing question prompt list for patients to use throughout the diagnostic process.

Methods

Medline and Google Scholar were searched to identify question lists in the peer-reviewed literature. Organizational websites and a search engine were searched to identify question lists in the gray literature. Articles and resources were screened for eligibility and data were abstracted. Interrater reliability (K = 0.875) was achieved.

Results

A total of 5509 questions from 235 resources met inclusion criteria. Most questions (n = 4243, 77.02%) were found in the gray literature. Question lists included an average of 23.44 questions. Questions were most commonly coded along the diagnostic process categories of treatment (2434 questions from 250 resources), communication of the diagnosis (1160 questions, 204 resources), and outcomes (766 questions, 172 resources).

Conclusions

Despite recommendations for patients to ask questions, most question prompt lists focus on later stages of the diagnostic process such as communication of the diagnosis, treatment, and outcomes. Further research is needed to identify and prioritize diagnostic-related questions from the patient perspective and to develop simple, usable guidance on question-asking to improve patient safety across the diagnostic continuum.
Inborn errors of immunity and invasive fungal infections: presentation and management
Authors: Paccoud Olivier , Warris Adilia , Puel Anne , Lanternier Fanny
Published: September 2024

Purpose of review

We review the clinical presentations of invasive fungal infections in a selection of inborn errors of immunity. In addition, we review the particularities of their management, including antifungal therapy, prophylaxis, and immunomodulatory treatments.

Recent findings

Patients with chronic granulomatous disease and with signal transducer and activator of transcription 3 (STAT3) deficiency are particularly prone to aspergillosis. Mold-active antifungal prophylaxis should be prescribed to all patients with chronic granulomatous disease, and in patients with STAT3 deficiency and underlying parenchymal lung disease. Invasive fungal infections are rare in patients with STAT1 gain-of-function mutations, while the clinical phenotype of caspase-associated recruitment domain-containing protein 9 deficiency encompasses a wide range of superficial and invasive fungal infections. Most patients with inborn errors of immunity and invasive fungal infections require prolonged durations of antifungals. Hematopoietic stem cell transplantation should be considered early for patients with chronic granulomatous disease, but results have been more mixed for other inborn errors of immunity with active invasive fungal infections.

Inborn errors of immunity can confer increased susceptibility to a variety of invasive fungal infections, which can present with specific clinical and radiological features. Management of fungal infections in these patients is often challenging, and relies on a combination of antimicrobial prophylaxis, antifungal treatments, and immunomodulation.
Clinical Efficacy of Bionic Blepharoplasty Using the Flexible Suspension and Semiflexible Suspension Double-Insurance Methods
Authors: He Zhigang , Gu Xianbin , Chen Lisha , Liu Wenjing , Yi Yangyan , Yang Juanmin
Published: September 2024

Objective:

To investigate the clinical effect of the double insurance method of flexible suspension and semiflexible suspension in bionic blepharoplasty.

Methods:

Between January 2020 and January 2022, a total of 115 patients (230 eyes) underwent double eyelid plastic surgery with flexible suspension and semiflexible suspension. Herein, we present a new type of double eyelid surgery that preserves the orbicular muscle of the anterior tarsus without removing the tissue. First, the loose fatty fascia layer between the anterior tarsus and the orbicularis oculi muscle was completely removed to a distance of 2 mm from the base of the eyelashes, leaving the compact pretarsal levator aponeurosis. Then, the anterior tarsus orbicularis oculi muscle and the upper levator aponeurosis were sutured and fixed (flexible suspension). Finally, the skin and the upper levator aponeurosis were sutured in the flexible suspension space (semiflexible suspension).

Results:

Six months after surgery, the patient’s double eyelid shape had recovered well, and the satisfaction rate reached 97.3%. Among the unsatisfied patients, 1 patient had a single-focused shallow eyelid line which was associated with postoperative hematoma, and 2 patients felt that the double eyelid line was narrow. All 3 patients achieved satisfactory results after reoperation.

Conclusions:

The bionic double eyelid method with flexible suspension and semiflexible suspension can restore the natural double eyelid anatomy very well by reconstructing the connection between the orbicularis oculi muscle or skin and the upper palpebral levator aponeurosis. After the operation, the incisions healed quickly and smoothly. The eyelid depression and fleshy feeling were not obvious when the eyes were closed. Consequently, the patient’s satisfaction was very high.
Divorce Among Surgeons and Other Physicians in the United States
Authors: Stearns Stephen A. , Farid Alexander R. , Jena Anupam B.
Published: September 2024

Objective:

To compare divorce prevalence among surgeons with that of nonsurgeon physicians.

Summary Background Data:

The demanding nature of a career in surgery uniquely challenges the social well-being of a surgeon; however, its impact on marital health has not yet been well described.

Methods:

A cross-sectional study was conducted using publicly available US Census data from 2017 to 2021 to investigate the prevalence of divorce across different occupations. Survey respondents were divided into 2 groups, surgeons and nonsurgeon physicians, with the remaining Census participants as a control. All participants under the age of 18 were excluded to focus on the US adult population. The lifetime prevalence of divorce was measured across occupations, and multivariable logistic regression analyses were performed to identify factors that were independently associated with divorce. Secondarily, the occurrence of more than one marriage was used to supplement the understanding of marital health.

Results:

A total of 3171 surgeons and 51,660 nonsurgeon physicians were identified, with both groups similarly aged (51.6 and 50.2 y, respectively) and predominately male (82.9% and 61.9%, respectively). In unadjusted analysis, 21.3% (676/3,171) of surgeons had undergone a divorce compared with only 17.9% (9252/51,660) of nonsurgeon physicians, a 19% increase in risk of divorce [risk ratio (RR)=1.19; 95% CI, 1.11–1.28]. Both surgeons and nonsurgeon physicians were significantly less likely to report being divorced compared with the general population. The increased divorce prevalence among surgeons persisted in multivariable analysis that adjusted for age, age at the time of marriage, sex, race, income, hours worked per week, and the number of children in the household, with surgeons experiencing a 22% increased prevalence of divorce over nonsurgical physicians [adjusted divorce prevalence of 21.8% vs 18.7%, respectively; odds ratio (OR)=1.22; 95% CI, 1.09–1.35]. In subgroup analysis, the finding of higher divorce prevalence for surgeons over nonsurgeon physicians was concentrated among men (adjusted divorce prevalence: 22.6% of male surgeons vs 18.9% of male nonsurgeon physicians; adjusted OR 1.26, 95% CI, 1.11–1.42), White (adjusted divorce prevalence: 22.4% of white surgeons vs 19.1% of White nonsurgeons; adjusted OR 1.22, 95% CI, 1.09–1.38) and Asian surgeons (adjusted divorce prevalence: 12.0% of Asian surgeons vs 8.1% of Asian nonsurgeons; adjusted OR 1.55, 95% CI, 1.06–2.26), with the effect not present in other measured subgroups.

Conclusions:

Both surgeons and physicians have lower divorce prevalence than the general population. Surgeons exhibit higher prevalence of divorce compared with nonsurgeon physicians, with measured demographic and work characteristics insufficient to explain this difference.
Movement bias in asymmetric landscapes and its impact on population distribution and critical habitat size
Authors: Dornelas Vivian , de Castro Pablo , Calabrese Justin M. , Fagan William F. , Martinez-Garcia Ricardo
Published: September 2024

Ecologists have long investigated how demographic and movement parameters determine the spatial distribution and critical habitat size of a population. However, most models oversimplify movement behaviour, neglecting how landscape heterogeneity influences individual movement. We relax this assumption and introduce a reaction–advection–diffusion equation that describes population dynamics when individuals exhibit space-dependent movement bias toward preferred regions. Our model incorporates two types of these preferred regions: a high-quality habitat patch, termed ‘habitat’, which is included to model avoidance of degraded habitats like deforested regions; and a preferred location, such as a chemoattractant source or a watering hole, that we allow to be asymmetrically located with respect to habitat edges. In this scenario, the critical habitat size depends on both the relative position of the preferred location and the movement bias intensities. When preferred locations are near habitat edges, the critical habitat size can decrease when diffusion increases, a phenomenon called the drift paradox. Also, ecological traps arise when the habitat overcrowds due to excessive attractiveness or the preferred location is near a low-quality region. Our results highlight the importance of species-specific movement behaviour and habitat preference as drivers of population dynamics in fragmented landscapes and, therefore, in the design of protected areas.
Whole genome sequences of marine bacteria presenting the ability to promote the growth of the diatom Phaeodactylum tricornutum
Authors: Martins Rodrigo , Bertrand Constança , Quintas-Nunes Francisco , Reynolds-Brandão Pedro , Barreto Crespo Maria , Nascimento Francisco X
Published: September 2024

2. Abstract

We describe the whole genome sequences of seven diverse marine bacteria isolated from Portuguese environments that presented the ability of promoting the growth of the model diatom, Phaeodactylum tricornutum. The bacterial genome sequences will contribute for the study of genetic and molecular mechanisms involved in diatom-bacteria interactions.
A novel case of Staphylococcus pseudintermedius aortitis
Authors: Jones Dione , Lim Matthew , Olenski Maxwell
Published: September 2024

Staphylococcus pseudintermedius is a common commensal and opportunistic canine pathogen with emerging pathogenicity in humans. We describe the first case of invasive S. pseudintermedius infection causing aortitis and mycotic aneurysm in an 83-year-old patient, treated successfully with flucloxacillin. This case highlights the potential for S. pseudintermedius to cause serious endovascular infection in humans.
Intranasal dantrolene nanoparticles inhibit lipopolysaccharide-induced depression and anxiety behavior in mice
Authors: Liu Jia , Lu Yan , Bhuiyan Piplu , Gruttner Jacob , Louis Lauren St. , Yi Yutong , Liang Ge , Wei Huafeng
Published: September 2024

This study investigates the therapeutic effectiveness of intranasal dantrolene nanoparticles pretreatment to inhibit lipopolysaccharide (LPS)-induced pathological inflammation and synapse destruction and depressive and anxiety behavior in mice. Both wild-type (WT) B6SJLF1/J and 5XFAD adult mice (5-10 months old) were pretreated with intranasal dantrolene nanoparticles (dantrolene: 5mg/kg), daily, Monday to Friday, 5 days per week, for 4 weeks. Then, mice were treated with intraperitoneal injection of LPS (5mg/kg) for one time. Behavioral tests for depression, anxiety and side effects were performed 24 hours after a one-time LPS injection. Biomarkers for pyroptosis-related inflammation cytokines (IL-1β and IL-18) in blood and brains were measured using enzyme-linked immunosorbent assay (ELISA) and immunoblotting, respectively. The changes of primary proteins activation inflammatory pyroptosis (NLRP3: NLR family pyrin domain containing 3, Caspase-1, N-GSDMD: N terminal protein gasdermin D) and synapse proteins (PSD-95 and synpatin-1) in brains were measured using immunoblotting. Intranasal dantrolene nanoparticles robustly inhibited LPS-induced depression and anxiety behavior in both WT and 5XFAD mice, without obvious side effects. Intranasal dantrolene nanoparticles significantly inhibited LPS-induced pathological elevation of IL-1β and IL-18 in the blood and synapse loss in the brain. Intranasal dantrolene nanoparticles trended to inhibit LPS-induced elevation of IL1β and IL-18 and the pyroptosis activation proteins in the brain in both type of mice. In conclusion, intranasal dantrolene nanoparticles demonstrated neuroprotection against inflammation mediated depression and anxiety behaviors and should be studied furthermore as a future effective drug treatment of major depression disorder or anxiety psychiatric disorder, especially in AD patients.
Structure-Based Computational Analysis of Interactions between Insulin Receptor and Insulin Inhibitory Receptor
Authors: Li Victor , Wu Yinghao
Published: September 2024

The recently discovered insulin inhibitory receptor (inceptor) plays a crucial role in insulin resistance and diabetes by reducing the insulin receptor count on cell membranes, resulting in higher blood glucose levels and decreased insulin sensitivity. Therefore, understanding the mechanism of how the inceptor insulin receptor complex interacts is exceedingly important. This study uses computational drug discovery to inhibit this interaction. Initially, we employed AlphaFold-Multimer to model the inceptor-insulin receptor protein complex and subsequently identified specific inceptor residues likely involved in binding to the insulin receptor. Through virtual screening, thousands of potential small molecules were found to bind to the inceptor, and 10 with the highest probability were chosen for docking. Beta-L-fucose, beta-D-fucose, and alpha-L-fucose showed the most promising binding energies, meaning these three small molecules can effectively interrupt the binding between the complex. We also computationally mutated the binding site of the insulin receptor and calculated the change in binding energy of the inceptor insulin receptor complex, the most dramatic being a 0.4 kcal mol^-1 change when Arginine mutated to Tryptophan at residue 926. Our study suggests that the mutations led to disease primarily due to the change in interactions of the inceptor insulin receptor complex.
Bulk-level maps of pioneer factor binding dynamics during Drosophila maternal-to-zygotic transition
Authors: Dima Sadia Siddika , Reeves Gregory T.
Published: September 2024

Gene regulation by transcription factors (TFs) binding cognate sequences is of paramount importance. For example, the TFs Zelda (Zld) and GAGA factor (GAF) are widely acknowledged for pioneering gene activation during zygotic genome activation (ZGA) inDrosophila. However, quantitative dose/response relationships between bulk TF concentration and the DNA binding, an event tied to transcriptional activity, remain elusive. Here, we map these relationships during ZGA: a crucial step in metazoan development. To map the dose/response relationship between nuclear concentration and DNA binding, we performed raster image correlation spectroscopy, a method that can measure concentration and binding of fluorescent molecules. We found that, although Zld concentration increases over time, its DNA binding in the transcriptionally active regions decreases, consistent with its function as an activator for early genes. In contrast, GAF DNA binding is nearly linear with its concentration, which sharply increases during the major wave, implicating it in the major wave. This study provides key insights into the properties of the two factors and puts forward a quantitative approach that can be used for other TFs to study transcriptional regulation.
Scalable identification of lineage-specific gene regulatory networks from metacells with NetID
Authors: Wang Weixu , Wang Yichen , Lyu Ruiqi , Grün Dominic
Published: September 2024

The identification of gene regulatory networks (GRN) governing distinct cell fates in multilineage cellular differentiation systems is of critical importance for understanding cell fate decision. Single-cell RNA-sequencing (scRNA-seq) provides a powerful tool for the quantification of gene-level co-variation across the cell state manifold. However, accurate GRN reconstruction is hampered by the sparsity of scRNA-seq data introducing substantial technical noise. Moreover, the high dimensionality of typical scRNA-seq datasets limits the scalability of available approaches. To overcome these challenges, and to facilitate the inference of lineage-specific GRNs with directed regulator-target relations, we introduce NetID. This approach optimizes coverage of the cell state manifold by homogenous metacells and avoids spurious gene-gene correlations observed with available imputation methods. Benchmarking demonstrates superior performance of NetID compared to imputation-based GRN inference. By incorporating cell fate probability information, NetID facilitates prediction of lineage-specific GRNs and recovers known network motifs centered around lineage-determining transcription factors governing bone marrow hematopoiesis, making it a powerful toolkit for deciphering the gene regulatory control of cellular differentiation from large-scale single-cell transcriptome data.
A can of worms: estimating the global number of earthworm species
Authors: Decaëns Thibaud , Brown George G. , Cameron Erin K. , Csuzdi Csaba , Eisenhauer Nico , Gérard Sylvain , Goulpeau Arnaud , Hedde Mickaël , James Samuel W. , Lapied Emmanuel , Maggia Marie-Eugénie , Marchán Daniel F. , Mathieu Jérôme , Phillips Helen R. P. , Marcon Eric
Published: September 2024

Estimating the overall number of species for a given taxon is a central issue in ecology and conservation biology. It should be particularly topical in the case of soil organisms, which represent the majority of known species, but still suffer from a considerable taxonomic knowledge deficit. We propose here an estimation of the global number of earthworm species based on the Joppa approach, which models taxonomic effort over time in order to estimate the total number of known and as yet unknown species in a given taxa. Our Bayesian estimation of this model allows us to propose a global diversity of the order of 30,000 species. However, the uncertainty around this estimate is considerable due to severe undersampling and as the model cannot unambiguously decide whether we are describing few species because of a small pool of as yet unknown species, or because of a lack of taxonomic efficiency. This means that the 5,679 species and subspecies already described only represent around 20% of the global number of earthworm species. Considering the current rate of new species description, we calculate that it would take at least 120 years to describe all the species existing on Earth. We discuss the strategies that could be developed to reduce the magnitude of this taxonomic deficit.
ROBI: a Robust and Optimized Biomarker Identifier to increase the likelihood of discovering relevant radiomic features
Authors: Rebaud Louis , Capobianco Nicolò , Sarkozy Clémentine , Cottereau Anne-Ségolène , Vercellino Laetitia , Casasnovas Olivier , Thieblemont Catherine , Spottiswoode Bruce , Buvat Irène
Published: September 2024

Objectives

The Robust and Optimized Biomarker Identifier (ROBI) feature selection pipeline is introduced to improve the identification of informative biomarkers coding information not already captured by existing features. It aims to accurately maximize the number of discoveries while minimizing and estimating the number of false positives (FP) with an adjustable selection stringency.

Methods

500 synthetic datasets and retrospective data of 378 Diffuse Large B Cell Lymphoma (DLBCL) patients were used for validation. On the DLBCL data, two established radiomic biomarkers, TMTV and Dmax, were measured from the 18F-FDG PET/CT scans, and 10,000 random ones were generated. Selection was performed and verified on each dataset. The efficacy of ROBI has been compared to methods controlling for multiple testing and a Cox model with Elasticnet penalty.

Results

On synthetic datasets, ROBI selected significantly more true positives (TP) than FP (p < 0.001), and for 99.3% of datasets, the number of FP was within the estimated 95% confidence interval. ROBI significantly increased the number of TP compared to usual feature selection methods (p < 0.001). On retrospective data, ROBI selected the two established biomarkers and one random biomarker and estimated 95% chance of selecting 0 or 1 FP and a probability of 0.0014 of selecting only FP. Bonferroni correction selected no feature, and Elasticnet selected 101 spurious features and discarded TMTV.

Conclusion

ROBI selected relevant biomarkers while effectively controlling for FPs, outperforming conventional selection methods. This underscores its potential as a valuable asset for biomarker discovery.

Highlights

ROBI is a feature selection tool capable of screening thousands of features.

It enables systematic evaluation of numerous radiomic features while minimizing false discoveries.

ROBI was validated on synthetic and real datasets, outperforming other selection techniques.
A prebiotic diet intervention can restore faecal short chain fatty acids in Parkinson's Disease yet fails to restore the gut microbiome homeostasis
Authors: Bedarf Janis Rebecca , Romano Stefano , Heinzmann Silke Sophie , Duncan Anthony , Traka Maria H , Ng Duncan , Segovia-Lizano Daniella , Simon Marie-Christine , Narbad Arjan , Wuellner Ullrich , Hildebrand Falk
Published: September 2024

ABSTRACT Despite extensive research, current treatment of Parkinson's Disease (PD) remains symptomatic and disease modifying approaches are urgently required. A promising approach is to target the gut-brain-axis by modifying the intestinal microbiota and the herein produced metabolites. We decided to test this approach by modifying key metabolites of bacterial intestinal fermentation: short chain fatty acids (SCFA), known to be decreased in PD patients. A prospective, controlled pilot study was conducted in 11 couples, with one PD patient and healthy spouse as control (CO) each. Participants followed a 4-week diet rich in dietary fibre in addition to the intake of a prebiotic sirup (Lactulose). Metagenomes and metabolites of the gut microbiota, urinary metabolites and clinical characteristics were assessed. The short-term dietary intervention significantly augmented gastrointestinal SCFA production, likely associated with increased Bifidobacteria spp. PD associated gastrointestinal symptoms improved with increasing SCFA levels. The pre-existing bacterial dysbiosis associated with PD, such as depletion of genera Blautia, Dorea, and Erysipelatoclostridium in PD, persisted within the study period. Some pathobionts, i.e. Klebsiella, were reduced after the intervention. Bacterial metabolite composition (both faecal and urine metabolomes) shifted towards the composition of the healthy control in PD after the intervention. Among these brain-relevant gut metabolic functions improved in PD patients, such as S-Adenosyl methionine (SAM), 3,4-Dihydroxyphenylacetic acid (DOPAC), Glutathione (GSH), Tryptophan and inositol related changes, involved in neuroprotective and antioxidant pathways. Despite the small cohort size and short-term study period a minor dietary intervention was sufficient to improve gastrointestinal symptoms in PD and altered metabolic parameters in a presumed neuroprotective manner, warranting further investigation in larger cohorts.
Altered food liking in depression is driven by macronutrient composition
Authors: Thurn Lilly , Schulz Corinna , Borgmann Diba , Klaus Johannes , Ellinger Sabine , Walter Martin , Kroemer Nils B.
Published: September 2024

Major depressive disorder (MDD) is characterized by changes in appetite and body weight as well as blunted reward sensitivity (“anhedonia”). However, it is not well understood which mechanisms are driving changes in reward sensitivity, specifically regarding food. Here, we used a sample of 117 participants (54 patients with MDD; 63 healthy control participants, HCP) who completed a food cue reactivity (FCR) task with ratings of wanting and liking for 60 food and 20 non-food items. To evaluate which components of the food may contribute to altered ratings in depression, we tested for associations with macronutrients of the depicted items. In line with previous studies, we found reduced ratings of food wanting (p= .003), but not liking (p= .23) in patients with MDD compared to matched HCPs. Adding macronutrient composition to the models of wanting and liking substantially improved their fit (ps < .001). Compared to carbohydrate-rich foods, patients with MDD reported lower liking and wanting ratings for high-fat and high-protein foods. Moreover, patients with MDD showed weaker correlations in their preferences for carbohydrate-versus fat- or protein-rich foods (ps < .001), pointing to potential disturbances in metabolic signaling. To conclude, our results suggest that depression-related alterations in food reward ratings are more specific to the macronutrient composition of the food than previously anticipated, hinting at disturbances in gut-brain signaling. These findings raise the intriguing question whether interventions targeting the gut could help normalize aberrant reward signals for foods rich in fat or protein.

Abstract Figure
Management of Dementia in a Resource-Constrained Sub-Saharan African Setting: Outcome of a Retrospective Survey of Clinical Practice in the Only Neuropsychiatric Facility in Northeastern Nigeria
Authors: Wakawa Ibrahim Abdu , Musami Umar Baba , Kwairanga Suleiman Hamidu , Ogualili Placidus Nwankuba , Mahmood Mohammed Yusuf , Fugu Muhammad Abba , Gimba Mohammed Mala , Allamin Muktar Mohammed , Abbas Zaharudeen Umar , Sunkani Muhammad Kawu , Yaganami Zainab Bukar , Kadau Fatima Mustapha , Sani Nasir Muhammad , Danmallam Peter , Nanjul Luka , Babazau Larema , Muhammad Zaid , Goni Baba Waru , Machina Babagana Kundi , Karch Celeste M. , Udeh-Momoh Chinedu , Karikari Thomas K. , Onyike Chiadi U. , Maina Mahmoud Bukar
Published: September 2024

Introduction

Dementia prevalence is rising in sub-Saharan Africa due to a combination of factors, including population growth and aging. In resource-constrained settings, such as Northeastern Nigeria, dementia management is challenged by delayed diagnosis and limited specialist care. This study evaluates the burden of dementia and its management at the Federal Neuropsychiatric Hospital Maiduguri (FNHM), the only neuropsychiatric facility in Northeastern Nigeria. The study aims to provide insights into current dementia trends and practices and identify key areas for improvement.

Methods

A retrospective analysis of patient records at FNPH Maiduguri was conducted, including patients aged 60 and above diagnosed with dementia between 1999 and 2023. Data on patient demographics, dementia subtypes, comorbidities, symptoms, diagnostic investigations, and treatment modalities were analysed.

Results

The Available record from the hospital health records register showed that the total number of diagnosed cases of dementia in the FNHM is 1,216 cases with a male predominance (56%). Alzheimer’s disease was the most common subtype (60.5%), followed by vascular dementia (24.5%). Hypertension was the most frequently reported comorbidity (41.6%). Cognitive symptoms, particularly memory loss, were reported in all cases, while behavioural symptoms, such as agitation and hallucinations, were reported in some cases. The most commonly administered treatments included cognitive enhancers (donepezil), supplements (gingko biloba), and non-drug therapies (psychoeducation). However, 70.9% of patients were lost to follow-up, highlighting a critical gap in long-term care.

Conclusion

The increasing burden of dementia at the only neuropsychiatric facility in Northeastern Nigeria highlights the urgent need for investments and targeted interventions. Enhancing patient engagement, strengthening follow-up systems, and expanding diagnostic and treatment capacities will improve care outcomes and address the growing demands for dementia management in this underserved region.
The induction of dissociative states: A meta-analysis
Authors: Brake Benjamin , Wieder Lillian , Hughes Natasha , Saravia Lalinde Ivonne , Marr Danielle , Geagea Dali , Pick Susannah , Reinders Antje A. T. S. , Kamboj Sunjeev K. , Thompson Trevor , Terhune Devin B.
Published: September 2024

Objective

Dissociative states, characterised by discontinuities in awareness and perception, occur in a diverse array of psychiatric disorders and contexts. Dissociative states have been modeled in the laboratory through various induction methods but relatively little is known about the efficacy and comparability of different experimental methods.

Methods

This meta-analysis quantified dissociative states, as indexed by a standardised instrument (Clinician Administered Dissociative States Scale), at baseline in varied diagnostic groups and in response to different experimental induction methods (psychological techniques and pharmacological agents) in both clinical and non-clinical samples. Primary outcomes were state dissociation effect sizes (Hedges’sg) (PROSPERO registration CRD42022384886).

Results

2,214 papers were screened, yielding 150 eligible articles and 251 effect sizes comprising 7,190 individuals. High levels of baseline state dissociation were observed in multiple diagnostic groups relative to controls, with the largest effects found in post-traumatic stress disorder (PTSD). In controlled experiments, induced state dissociation was most pronounced in response to mirror-gazing, ayahuasca, ketamine, cannabis, MDMA, and nitrous oxide relative, with effects comparable to or exceeding baseline state dissociation in PTSD. The effect sizes were characterised by pronounced heterogeneity but were not reliably associated with methodological features of the original studies.

Conclusions

Elevated state dissociation is present in multiple diagnostic groups and comparable or higher levels can be reliably induced in controlled experiments using psychological techniques and pharmacological agents. These results demonstrate the efficacy of several methods for experimentally modelling dissociation and have implications for measuring adverse events and predicting outcomes in clinical interventions involving pharmacological agents.
Use of Metagenomic Microbial Plasma Cell-Free DNA Next-Generation Sequencing Assay in Outpatient Rheumatology Practice
Authors: Jenkins Rachel , Samec Matthew , Arment Courtney , Warrington Kenneth J. , Davis John M. , Koster Matthew J.
Published: September 2024

Objectives

To assess the utility of a metagenomic microbial plasma cell-free DNA next-generation sequencing assay (Karius TestTM; KT) in the evaluation of patients in an outpatient rheumatology practice.

Methods

All patients with a KT ordered and obtained by a rheumatology provider in the outpatient setting from 1 January 2020 through 31 December 2022 were retrospectively identified. Demographic, clinical, laboratory, radiologic, histopathology, and microbial studies were abstracted. Indication for KT testing was categorized. KT results were defined based on positive result and clinical relevance regarding the symptoms under investigation at the time of the rheumatologic investigation. Review of cases three months after KT was undertaken to determine clinical outcome.

Results

150 patients with a KT were included (53% female, mean age 52 years). The reason for KT was evaluation of atypical presentation of rheumatic disease (80%), assessing flare versus infection in patient on immunosuppression (16.7%), and fever of unknown origin (3.3%). 24 (16%) KTs were positive, 6 of which were considered clinically relevant and altered the final diagnosis and treatment. Of the 126 negative KTs, 5 (4%) were found to have a clinically relevant infection by conventional testing methodologies.

Conclusions

In this large retrospective cohort study, the most frequent reason for KT utilization was an atypical presentation of rheumatic disease. 25% of positive KTs altered the final diagnosis and treatment, whereas a false-negative rate of 4% was observed. KT has utility in the outpatient rheumatology assessment. Further delineation of which patients are best suited for KT testing remains to be defined.

Key messages

Use of microbial cell free DNA testing assisted in differentiating between atypical infection and rheumatologic presentation

Further studies are needed to define the most optimal patient selection for maximizing mcfDNA technologies in the rheumatology outpatient setting
The Greenland shark (Somniosus microcephalus) genome provides insights into extreme longevity
Authors: Sahm Arne , Cherkasov Alexander , Liu Hequn , Voronov Danila , Siniuk Kanstantsin , Schwarz Robert , Ohlenschlaeger Oliver , Foerste Silke , Bens Martin , Groth Marco , Goerlich Ivonne , Paturej Sonia , Klages Sven , Braendl Bjoern , Olsen Jesper , Bushnell Peter , Poulsen Amalie Bech , Ferrando Sara , Garibaldi Fulvio , Drago Davide Lorenzo , Tozzini Eva Terzibasi , Mueller Franz-Josef , Fischer Martin , Kretzmer Helene , Domenici Paolo , Steffensen John Fleng , Cellerino Alessandro , Hoffmann Steve
Published: September 2024

The Greenland shark (Somniosus microcephalus) is the longest-lived vertebrate known, with an estimated lifespan of ~ 400 years. Here, we present a chromosome-level assembly of the 6.45 Gb Greenland shark, rendering it one of the largest non-tetrapod genomes sequenced so far. Expansion of the genome is mostly accounted for by a substantial expansion of transposable elements. Using public shark genomes as a comparison, we found that genes specifically duplicated in the Greenland shark form a functionally connected network enriched for DNA repair function. Furthermore, we identified a unique insertion in the conserved C-terminal region of the key tumor suppressor p53. We also provide a public browser to explore its genome.
Adverse Events During a 12-month Multi-Site and Dose-Response Aerobic Exercise Intervention
Authors: Vidoni Eric D. , Grove George , Szabo-Reed Amanda N. , Key Mickeal N. , Huang Haiqing , Burns Jeffrey M. , Hillman Charles H. , Jakicic John M. , Kang Chaeryon , Kramer Arthur F. , McAuley Edward , Wan Lu , Hawes Tera , White Sydney S. , Erickson Kirk I.
Published: September 2024

Purpose

This study aimed to assess the incidence of adverse events (AE) in older adults participating in a year-long exercise intervention, investigating potential dose-response relationships between exercise intensity and AE frequency, and identifying demographic factors associated with AE risk.

Methods

A total of 648 older adults were randomized into one of three exercise groups: low-intensity stretching and toning (S&T), 150 minutes of aerobic exercise per week (150Ex), or 225 minutes of aerobic exercise per week (225Ex). Adverse events were tracked during the intervention, with event rates calculated based on participant adherence and time in the study. Generalized linear models were employed to compare AE incidence across groups. Post hoc comparisons were used to calculate incidence rate ratios (IRRs) for AE between groups, adjusting for multiple comparisons.

Results

Overall, 306 AE were reported, with 44% related to the intervention. No significant dose-response relationship was observed for all-cause AE between groups. However, intervention-related AE were more frequent in the aerobic exercise groups. Participants in the 150Ex group had a 77% higher rate of intervention-related AE compared to the S&T group, and the 225Ex group had an 88% higher rate. Higher adherence was associated with fewer all-cause AE, and greater comorbid burden was associated with more AE.

Conclusions

While aerobic exercise increased the risk of intervention-related AE, the overall risk remained low. Higher adherence to the exercise regimen was associated with fewer AE. These findings suggest aerobic exercise is generally safe in older adults, with the benefits outweighing the risks.
Deciphering TB-IRIS in HIV Patients: A Comprehensive Clinical and Microbiological Analysis
Authors: Gupta Priyanka , Tripathi Anil Kumar , Singh Kaleshwar Prasad , Jain Amita , Gupta Abhishek
Published: September 2024

Background

Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) coinfection presents a complex clinical challenge, with Tuberculosis-Immune Reconstitution Inflammatory Syndrome (TB-IRIS) emerging as a significant complication following antiretroviral therapy (ART) initiation. Understanding the clinical and microbiological characteristics of TB-IRIS is crucial for improving patient outcomes.

Methods

This prospective cohort study included 400 HIV-positive patients from the ART centre at King George’s Medical University, Lucknow, India. Patients were categorized based on TB status and monitored for the development of TB-IRIS following ART initiation. Clinical data, CD4 counts, and microbiological analyses, including drug susceptibility testing, were conducted. TB-IRIS was classified as paradoxical or unmasking, and outcomes were assessed over a one-year period.

Results

Among the 400 patients, 38 (9.5%) developed TB-IRIS, with 31 (81.6%) presenting unmasking TB-IRIS and 7 (18.4%) paradoxical TB-IRIS. Tubercular meningitis (TBM) was the most common manifestation (47.3%), followed by pulmonary TB (29.0%). The incidence of TB-IRIS was higher (15.4%) in patients who initiated ART within one month of starting anti-tuberculosis therapy (ATT) compared to those who started ART later (5.5%). A lower baseline CD4 count (<100 cells/µL) was significantly associated with a higher risk of TB-IRIS (p=0.003). The drug resistance analysis revealed 27.2% resistance to both isoniazid and rifampicin. Steroid therapy was administered to 13% of TB-IRIS patients. The overall cure/improvement rate was 71%, while the mortality rate was 23.6%. No patients discontinued ART during the study.

Conclusion

This study highlights the predominance of unmasking TB-IRIS in HIV patients initiating ART, particularly those with low baseline CD4 counts and early ART initiation post-ATT. The significant drug resistance observed underscores the need for robust diagnostic and treatment protocols. Improved management strategies are essential to enhance clinical outcomes in TB-IRIS patients.
Performance Evaluation of the Verily Numetric Watch sleep suite for digital sleep assessment against in-lab polysomnography
Authors: Nelson Benjamin W. , Saeb Sohrab , Barman Poulami , Verma Nishant , Allen Hannah , de Zambotti Massimiliano , Baker Fiona C. , Arra Nicole , Sridhar Niranjan , Sullivan Shannon S. , Plowman Scooter , Rainaldi Erin , Kapur Ritu , Shin Sooyoon
Published: September 2024

The goal was to evaluate the performance of a multi-sensor wrist-worn wearable device for generating 12 sleep measures in a diverse cohort. Our study technology was the sleep suite of the Verily Numetric Watch (VNW), using polysomnography (PSG) as reference during 1-night simultaneous recording in a sample of N=41 (18 male, age range: 18-78 years). We performed epoch-by-epoch comparisons for all measures. Key specific analyses were: core accuracy metrics for sleep vs wake classification; bias for continuous measures (Bland-Altman); Cohen’s kappa and accuracy for sleep stage classifications; and mean count difference and linearly weighted Cohen’s kappa for count metric. In addition, we performed subgroup analyses by sex, age, skin tone, body mass index, and arm hair density. Sensitivity and specificity (95% CI) of sleep versus wake classification were 0.97 (0.96, 0.98) and 0.66 (0.61, 0.71), respectively. Mean total sleep time bias was 14.55 minutes (1.61, 27.16); wake after sleep onset, −11.77 minutes (−23.89, 1.09); sleep efficiency, 3.15% (0.68, 5.57); sleep onset latency, −3.24 minutes (−9.38, 3.57); light-sleep duration, 3.78 minutes (−7.04, 15.06); deep-sleep duration, 3.91 minutes (−4.59, 12.60); rapid eye movement-sleep duration, 6.94 minutes (0.57, 13.04). Median difference for number of awakenings, 0.00 (0.00, 1.00); and overall accuracy of sleep stage classification, 0.78 (0.51, 0.88). Most measures showed statistically significant proportional biases and/or heteroscedasticity. Subgroup results appeared largely consistent with the overall group, although small samples preclude strong conclusions. These results support the use of VNW’s in classifying sleep versus wake, sleep stages, and for related overnight sleep measures.
Hypoxia impedes differentiation of cranial neural crest cells into derivatives relevant for craniofacial development
Authors: Schmid Theresa , Rodrian Gabriele , Kohler Alexander , Wegner Michael , Gölz Lina , Weider Matthias
Published: September 2024

Orofacial clefts are the second-most prevalent congenital malformation. Risk factors are multifactorial and include genetic components but also environmental factors. One environmental factor is hypoxia during pregnancy, caused for instance by tobacco smoking, medication or living at high altitudes. Knowledge about the molecular link between hypoxia and orofacial clefts is at large. We here show that hypoxia has only modest effects on proliferating cranial neural crest cells, but dramatically influences their differentiation potential. We detected massive perturbations in their differentiation to chondrocytes, osteoblasts and smooth muscle cells. The transcriptional induction of the majority of regulated genes during each of these processes was grossly impaired by hypoxic conditions, as evidenced by genome-wide transcriptomic analyses. Bioinformatic analyses pointed to cytoskeletal organization and amino acid metabolism as two main processes compromised during all three differentiation pathways, and several orofacial cleft risk genes were among the genes with impaired induction during hypoxia. Our analyses reveal a drastic influence of hypoxia on the differentiation potential of cranial neural crest cells as a possible source for the occurrence of orofacial clefts.
MICROBIOTA DRIVES THE SEXUALLY DIMORPHIC INFECTION OUTCOMES IN MEALWORM BEETLES
Authors: Seal Srijan , Kumar Devashish , Thunga Pavankumar , Khangar Pawan , Gupta Manisha , Basu Dipendra Nath , Raychoudhury Rhitoban , Khan Imroze
Published: September 2024

Sexually dimorphic responses to pathogenic infections in animals may stem from sex-specific differences in their life history and immune investment. Recent evidence highlights that such sex-specific variations in immune responses can also be critically regulated by microbiota. However, direct experiments to test how microbiota jointly impacts sex-specific immunity and vulnerability to pathogens are still limited. To this end, we usedTenebrio molitorbeetles to first establish that sexes appear to differ in their microbiota composition and infection responses. Females were more vulnerable to bacterial infections and carried a higher bacterial load than males. When we depleted the microbiome, only females improved their post-infection survival, leading to a loss of sex-specific infection outcomes. Males, on the other hand, remained unaffected. Microbiota reconstitution (via feeding on faecal matter) of microbiota-depleted females increased their susceptibility to infection again, restoring the sexual dimorphism. We thus found a causal association between microbiome and infection responses. We also found reduced expression of an antimicrobial peptide tenecin 1 in females, which could be associated with their higher infection susceptibility, but such immune gene-vs-phenotypic associations were not consistent across microbiota manipulations. Immune strategies that are required to mediate the causal links between microbiome and infection response might thus vary with microbiota manipulations, warranting future investigations.
High-coverage, massively parallel sequencing of single-cell genomes with CAP-seq
Authors: Li Mengzhen , Zhai Xuanpei , Li Jie , Li Shiyan , Du Yanan , Zhang Jian , Zhang Rong , Luo Yuan , Wei Wu , Liu Yifan
Published: September 2024

Microorganisms dominate Earth’s ecosystems in both abundance and diversity. Studying these organisms relies on their genome information, but obtaining high-quality genomes has long been challenging due to technical limitations in genomic sequencing. Traditional genome sequencing methods are limited by the need to culture isolated strains, excluding unculturable taxa and restricting the study of complex communities. Metagenomics bypasses this but lacks single-cell resolution and often misses rare, critical species. Droplet-based single-cell genomics offers high-throughput genome library preparation but faces challenges like requiring complex microfluidic setups and low genome coverage. To address these challenges, we introduce CAP-seq, a high-throughput single-cell genomic sequencing method with markedly improved genome coverage and ease of use. CAP-seq employs semi-permeable compartments that allow reagent exchange while retaining large DNA fragments, enabling efficient genome processing. This innovation results in higher-quality single amplified genomes (SAGs) and significantly improves resolution. In validation tests with simple and complex microbial communities, CAP-seq yielded high-quality SAGs with over 50% genome coverage, capturing rare taxa more accurately and providing detailed insights into strain-level variation. CAP-seq thus offers a scalable, high-resolution solution for microbial genomic analysis, overcoming the limitations of droplet-based single-cell genomics and enhancing the study of complex microbial ecosystems.
Progressive overfilling of readily releasable pool underlies short-term facilitation at recurrent excitatory synapses in layer 2/3 of the rat prefrontal cortex
Authors: Shin Jiwoo , Lee Seung Yeon , Kim Yujin , Lee Suk-Ho
Published: September 2024

Short-term facilitation of recurrent excitatory synapses within the cortical network has been proposed to support persistent activity during working memory tasks, yet the underlying mechanisms remain poorly understood. We characterized short-term plasticity at the local excitatory synapses in layer 2/3 of the rat medial prefrontal cortex and studied its presynaptic mechanisms. Low-frequency stimulation induced slowly developing facilitation, whereas high-frequency stimulation initially induced strong depression followed by rapid facilitation. This non-monotonic delayed facilitation after a brief depression resulted from a high vesicular fusion probability and slow activation of Ca2+-dependent vesicle replenishment, which led to the overfilling of release sites beyond their basal occupancy. Pharmacological and gene knockdown (KD) experiments revealed that the facilitation was mediated by phospholipase C/diacylglycerol signaling and synaptotagmin 7 (Syt7). Notably, Syt7 KD abolished facilitation and slowed the refilling rate of vesicles with high fusion probability. Furthermore, Syt7 deficiency in layer 2/3 pyramidal neurons impaired the acquisition of trace fear memory and reduced c-Fos activity. In conclusion, Ca2+- and Syt7-dependent overfilling of release sites mediates synaptic facilitation at L2/3 recurrent excitatory synapses and contributes to temporal associative learning.