bluuebunny/crossref_metadata_2025 huggingface dataset:
Nosocomial transmission ofAspergillus flavusin a neonatal intensive care unit: Long-term persistence in environment and interest of MALDI–ToF mass-spectrometry coupled with convolutional neural network for rapid clone recognition
Authors: Mohammad Noshine , Huguenin Antoine , Lefebvre Annick , Menvielle Laura , Toubas Dominique , Ranque Stéphane , Villena Isabelle , Tannier Xavier , Normand Anne-Cécile , Piarroux Renaud
Published: December 2023

Aspergillosis of the newborn remains a rare but severe disease. We report four cases of primary cutaneous Aspergillus flavus infections in premature newborns linked to incubators contamination by putative clonal strains. Our objective was to evaluate the ability of matrix-assisted laser desorption/ionisation time of flight (MALDI–TOF) coupled to convolutional neural network (CNN) for clone recognition in a context where only a very small number of strains are available for machine learning. Clinical and environmental A. flavus isolates (n = 64) were studied, 15 were epidemiologically related to the four cases. All strains were typed using microsatellite length polymorphism. We found a common genotype for 9/15 related strains. The isolates of this common genotype were selected to obtain a training dataset (6 clonal isolates/25 non-clonal) and a test dataset (3 clonal isolates/31 non-clonal), and spectra were analysed with a simple CNN model. On the test dataset using CNN model, all 31 non-clonal isolates were correctly classified, 2/3 clonal isolates were unambiguously correctly classified, whereas the third strain was undetermined (i.e., the CNN model was unable to discriminate between GT8 and non-GT8). Clonal strains of A. flavus have persisted in the neonatal intensive care unit for several years. Indeed, two strains of A. flavus isolated from incubators in September 2007 are identical to the strain responsible for the second case that occurred 3 years later.

MALDI–TOF is a promising tool for detecting clonal isolates of A. flavus using CNN even with a limited training set for limited cost and handling time.
Truncated, tilted discs as a possible source of Quasi-Periodic Oscillations
Authors: Bollimpalli D A , Fragile P C , Dewberry J W , Kluźniak W
Published: December 2023

Many accreting black holes and neutron stars exhibit rapid variability in their X-ray light curves, termed quasi-periodic oscillations (QPOs). The most commonly observed type is the low-frequency (≲10 Hz), type-C QPO, while only a handful of sources exhibit high-frequency QPOs (≳60 Hz). The leading model for the type-C QPO is Lense-Thirring precession of a hot, geometrically thick accretion flow that is misaligned with the black hole’s spin axis. However, existing versions of this model have not taken into account the effects of a surrounding, geometrically thin disc on the precessing, inner, geometrically thick flow. In Bollimpalli et. al 2023, using a set of GRMHD simulations of tilted, truncated accretion discs, we confirmed that the outer thin disc slows down the precession rate of the precessing torus, which has direct observational implications for type-C QPOs. In this paper, we provide a detailed analysis of those simulations and compare them with an aligned truncated disc simulation. We find that the misalignment of the disc excites additional variability in the inner hot flow, which is absent in the comparable aligned-disc simulations. This suggests that the misalignment may be a crucial requirement for producing QPOs. We attribute this variability to global vertical oscillations of the inner torus at epicyclic frequencies corresponding to the transition radius. This explanation is consistent with current observations of higher frequency QPOs in black hole X-ray binary systems.
Structure of the WYL-domain containing transcription activator, DriD, in complex with ssDNA effector and DNA target site
Authors: Schumacher Maria A , Cannistraci Emily , Salinas Raul , Lloyd Devin , Messner Ella , Gozzi Kevin
Published: December 2023

Transcription regulators play central roles in orchestrating responses to changing environmental conditions. Recently the Caulobacter crescentus transcription activator DriD, which belongs to the newly defined WYL-domain family, was shown to regulate DNA damage responses independent of the canonical SOS pathway. However, the molecular mechanisms by which DriD and other WYL-regulators sense environmental signals and recognize DNA are not well understood. We showed DriD DNA-binding is triggered by its interaction with ssDNA, which is produced during DNA damage. Here we describe the structure of the full-length C. crescentus DriD bound to both target DNA and effector ssDNA. DriD consists of an N-terminal winged-HTH (wHTH) domain, linker region, three-helix bundle, WYL-domain and C-terminal WCX-dimer domain. Strikingly, DriD binds DNA using a novel, asymmetric DNA-binding mechanism that results from different conformations adopted by the linker. Although the linker does not touch DNA, our data show that contacts it makes with the wHTH are key for specific DNA binding. The structure indicates how ssDNA-effector binding to the WYL-domain impacts wHTH DNA binding. In conclusion, we present the first structure of a WYL-activator bound to both effector and target DNA. The structure unveils a unique, asymmetric DNA binding mode that is likely conserved among WYL-activators.
Global Hfq-mediated RNA interactome of nitrogen starved Escherichia coli uncovers a conserved post-transcriptional regulatory axis required for optimal growth recovery
Authors: McQuail Josh , Matera Gianluca , Gräfenhan Tom , Bischler Thorsten , Haberkant Per , Stein Frank , Vogel Jörg , Wigneshweraraj Sivaramesh
Published: December 2023

The RNA binding protein Hfq has a central role in the post-transcription control of gene expression in many bacteria. Numerous studies have mapped the transcriptome-wide Hfq-mediated RNA–RNA interactions in growing bacteria or bacteria that have entered short-term growth-arrest. To what extent post-transcriptional regulation underpins gene expression in growth-arrested bacteria remains unknown. Here, we used nitrogen (N) starvation as a model to study the Hfq-mediated RNA interactome as Escherichia coli enter, experience, and exit long-term growth arrest. We observe that the Hfq-mediated RNA interactome undergoes extensive changes during N starvation, with the conserved SdsR sRNA making the most interactions with different mRNA targets exclusively in long-term N-starved E. coli. Taking a proteomics approach, we reveal that in growth-arrested cells SdsR influences gene expression far beyond its direct mRNA targets. We demonstrate that the absence of SdsR significantly compromises the ability of the mutant bacteria to recover growth competitively from the long-term N-starved state and uncover a conserved post-transcriptional regulatory axis which underpins this process.
Advancing fatigue management in healthcare: risk-based approaches that enhance health service delivery
Authors: Sprajcer M , Robinson A , Thomas M J W , Dawson D
Published: December 2023

Given the need for 24/7 healthcare services, fatigue is an inevitable consequence of work in this industry. A significant body of regulatory advice and hospital services have focused primarily on restricting work hours as the primary method of mitigating fatigue-related risk. Given the inevitability of fatigue, and the limited capacity of labour agreements to control risk, this commentary explores how the principles of fatigue risk management might be applied in a healthcare setting.
Long-term root electrotropism reveals habituation and hysteresis
Authors: Salvalaio Maddalena , Sena Giovanni
Published: December 2023

Plant roots sense many physical and chemical cues in soil, such as gravity, humidity, light, and chemical gradients, and respond by redirecting their growth toward or away from the source of the stimulus. This process is called tropism. While gravitropism is the tendency to follow the gravitational field downwards, electrotropism is the alignment of growth with external electric fields and the induced ionic currents. Although root tropisms are at the core of their ability to explore large volumes of soil in search of water and nutrients, the molecular and physical mechanisms underlying most of them remain poorly understood. We have previously provided a quantitative characterization of root electrotropism in Arabidopsis (Arabidopsis thaliana) primary roots exposed for 5 h to weak electric fields, showing that auxin asymmetric distribution is not necessary for root electrotropism but that cytokinin biosynthesis is. Here, we extend that study showing that long-term electrotropism is characterized by a complex behavior. We describe overshoot and habituation as key traits of long-term root electrotropism in Arabidopsis and provide quantitative data about the role of past exposures in the response to electric fields (hysteresis). On the molecular side, we show that cytokinin, although necessary for root electrotropism, is not asymmetrically distributed during the bending. Overall, the data presented here represent a step forward toward a better understanding of the complexity of root behavior and provide a quantitative platform for future studies on the molecular mechanisms of electrotropism.
Wake and non-rapid eye movement sleep dysfunction is associated with colonic neuropathology in Parkinson’s disease
Authors: Sadoc Mathilde , Clairembault Thomas , Coron Emmanuel , Berthomier Christian , Le Dily Séverine , Vavasseur Fabienne , Pavageau Albane , St. Louis Erik K , Péréon Yann , Neunlist Michel , Derkinderen Pascal , Leclair-Visonneau Laurène
Published: December 2023

Study Objectives

The body-first Parkinson’s disease (PD) hypothesis suggests initial gut Lewy body pathology initially propagates to the pons before reaching the substantia nigra, and subsequently progresses to the diencephalic and cortical levels, a disease course presumed to likely occur in PD with rapid eye movement sleep behavior disorder (RBD). We aimed to explore the potential association between colonic phosphorylated alpha-synuclein histopathology (PASH) and diencephalic or cortical dysfunction evidenced by non-rapid eye movement (NREM) sleep and wakefulness polysomnographic markers.

Methods

In a study involving 43 patients with PD who underwent clinical examination, rectosigmoidoscopy, and polysomnography, we detected PASH on colonic biopsies using whole-mount immunostaining. We performed a visual semi-quantitative analysis of NREM sleep and wake electroencephalography (EEG), confirmed it with automated quantification of spindle and slow wave features of NREM sleep, and the wake dominant frequency, and then determined probable Arizona PD stage classifications based on sleep and wake EEG features.

Results

The visual analysis aligned with the automated quantified spindle characteristics and the wake dominant frequency. Altered NREM sleep and wake parameters correlated with markers of PD severity, colonic PASH, and RBD diagnosis. Colonic PASH frequency also increased in parallel to probable Arizona PD stage classifications.

Conclusions

Colonic PASH is strongly associated with widespread brain sleep and wake dysfunction, suggesting an extensive diffusion of the pathologic process in PD. Visual and automated analyses of polysomnography signals provide useful markers to gauge covert brain dysfunction in PD.

Clinical Trial

Name: SYNAPark, URL: https://clinicaltrials.gov/study/NCT01748409, registration: NCT01748409
Effects of monensin and cashew nut-shell extract on bacterial community composition in a dual-flow continuous culture system
Authors: Sarmikasoglou Efstathios , Sumadong Phussorn , Roesch Luiz Fernando , Halima Sultana , Hikita Chie , Watanabe Tomonori , Faciola Antonio P
Published: December 2023

The objective of this study was to evaluate the effects of including monensin and two doses of CNSE in a high producing dairy cow diet on ruminal bacterial communities. A dual-flow continuous culture system was used in a replicated 4 × 4 Latin Square design. A basal diet was formulated to meet the requirements of a cow producing 45 kg of milk per d (17% crude protein and 27% starch). There were four experimental treatments: the basal diet without any feed additive (CON), 2.5 μM monensin (MON), 100 ppm CNSE granule (CNSE100), and 200 ppm CNSE granule (CNSE200). Samples were collected from the fluid and solid effluents at 3, 6, and 9 h after feeding; a composite of all time points was made for each fermenter within their respective fractions. Bacterial community composition was analyzed by sequencing the V4 region of the 16S rRNA gene using the Illumina MiSeq platform. Treatment responses for bacterial community structure were analyzed with the PERMANOVA test run with the R Vegan package. Treatment responses for correlations were analyzed with the CORR procedure of SAS. Orthogonal contrasts were used to test the effects of (1) ADD (CON vs. MON, CNSE100, and CNSE200); (2) MCN (MON vs. CNSE100 and CNSE200); and (3) DOSE (CNSE100 vs. CNSE200). Significance was declared at P ≤ 0.05. We observed that the relative abundance of Sharpea (P < 0.01), Mailhella (P = 0.05), Ruminococcus (P = 0.03), Eubacterium (P = 0.01), and Coprococcus (P < 0.01) from the liquid fraction and the relative abundance of Ruminococcus (P = 0.03) and Catonella (P = 0.02) from the solid fraction decreased, while the relative abundance of Syntrophococcus (P = 0.02) increased in response to MON when compared to CNSE treatments. Our results demonstrate that CNSE and monensin have similar effects on the major ruminal bacterial genera, while some differences were observed in some minor genera. Overall, the tested additives would affect the ruminal fermentation in a similar pattern.
SARS-CoV-2 infection in immunosuppression evolves sub-lineages which independently accumulate neutralization escape mutations
Authors: Lustig Gila , Ganga Yashica , Rodel Hylton E , Tegally Houriiyah , Khairallah Afrah , Jackson Laurelle , Cele Sandile , Khan Khadija , Jule Zesuliwe , Reedoy Kajal , Karim Farina , Bernstein Mallory , Ndung’u Thumbi , Moosa Mahomed-Yunus S , Archary Derseree , de Oliveira Tulio , Lessells Richard , Neher Richard A , Abdool Karim Salim S , Sigal Alex
Published: December 2023

One mechanism of variant formation may be evolution during long-term infection in immunosuppressed people. To understand the viral phenotypes evolved during such infection, we tested SARS-CoV-2 viruses evolved from an ancestral B.1 lineage infection lasting over 190 days post-diagnosis in an advanced HIV disease immunosuppressed individual. Sequence and phylogenetic analysis showed two evolving sub-lineages, with the second sub-lineage replacing the first sub-lineage in a seeming evolutionary sweep. Each sub-lineage independently evolved escape from neutralizing antibodies. The most evolved virus for the first sub-lineage (isolated day 34) and the second sub-lineage (isolated day 190) showed similar escape from ancestral SARS-CoV-2 and Delta-variant infection elicited neutralizing immunity despite having no spike mutations in common relative to the B.1 lineage. The day 190 isolate also evolved higher cell–cell fusion and faster viral replication and caused more cell death relative to virus isolated soon after diagnosis, though cell death was similar to day 34 first sub-lineage virus. These data show that SARS-CoV-2 strains in prolonged infection in a single individual can follow independent evolutionary trajectories which lead to neutralization escape and other changes in viral properties.
What we can and cannot learn from SARS-CoV-2 and animals in metagenomic samples from the Huanan market
Authors: Débarre Florence
Published: December 2023

While the exact context of the emergence of SARS-CoV-2 remains uncertain, data accumulated since 2020 have provided an increasingly more precise picture of Wuhan’s Huanan Seafood Wholesale Market, to which the earliest clusters of human cases of Covid-19 were linked. After the market closed on January 1st 2020, teams from the Chinese Center for Disease Control and Prevention collected environmental samples, and sequenced them. Metagenomic sequencing data from these samples were shared in early 2023. These data confirmed that non-human animals susceptible to SARS-CoV-2 were present in the market before it closed, but also that these animals were located in the side of the market with most human cases, and in a corner with comparatively more SARS-CoV-2-positive environmental samples. The environmental samples were however collected after abundant human-to-human transmission had taken place in the market, precluding any identification of a non-human animal host. Jesse Bloom recently investigated associations between SARS-CoV-2 and non-human animals, concluding that the data failed to indicate whether non-human animals were infected by SARS-CoV-2, despite this being an already acknowledged limitation of the data. Here I explain why a correlation analysis could not confidently conclude which hosts(s) may have shed SARS-CoV-2 in the market, and I rebut the suggestion that such analyses had been encouraged. I show that Bloom’s investigation ignores the temporal and spatial structure of the data, which led to incorrect interpretations. Finally, I show that criteria put forward by Bloom to identify the host(s) that shed environmental SARS-CoV-2 would also exclude humans. Progress on the topic of SARS-CoV-2’s origin requires a clear distinction between scientific studies and news articles (mis)interpreting them.
To have or not to have a penis? Phally polymorphism in minute, hermaphroditic gastropods from the Vertiginidae family
Authors: Książkiewicz Zofia , Sulikowska-Drozd Anna , von Proschwitz Ted , Rybak Michał
Published: December 2023

Phally polymorphism in snails offers an excellent opportunity to study the evolutionary basis of sexual polymorphism in animals. Phally polymorphism occurs when two or three sexual morphs co-occur in populations of hermaphroditic organisms. Euphallics have a fully developed and functional penis, hemiphallics have a reduced and non-functional penis, while aphallics have no penis. All morphs can self-fertilize, but only euphallics can donate sperm during copulation. In this study, we investigated the geographical pattern of phally polymorphism in minute Vertigo species by testing snails from Polish and Swedish populations. Considering the principle of resource allocation, we checked whether sexual morph reflects the size of the shell. Although the Swedish Vertigo snails tend to be smaller than the Polish ones, our results show no clear geographical pattern of sexual morph balance in the studied populations. Aphallics of V. angustior were bigger than the euphallics; conversely to V. substriata, where euphallics were bigger than aphallics. Such a result suggests a species-specific resource allocation towards the given sexual function. Since hemiphallics of V. antivertigo were smaller than euphallics, we discuss the possible trade-off when faced with resource depletion and the failure of attaining sexual maturity of euphallics.
State-related Electroencephalography Microstate Complexity during Propofol- and Esketamine-induced Unconsciousness
Authors: Liang Zhenhu , Tang Bo , Chang Yu , Wang Jing , Li Duan , Li Xiaoli , Wei Changwei
Published: December 2023

Background

Identifying the state-related “neural correlates of consciousness” for anesthetics-induced unconsciousness is challenging. Spatiotemporal complexity is a promising tool for investigating consciousness. The authors hypothesized that spatiotemporal complexity may serve as a state-related but not drug-related electroencephalography (EEG) indicator during an unconscious state induced by different anesthetic drugs (e.g., propofol and esketamine).

Methods

The authors recorded EEG from patients with unconsciousness induced by propofol (n = 10) and esketamine (n = 10). Both conventional microstate parameters and microstate complexity were analyzed. Spatiotemporal complexity was constructed by microstate sequences and complexity measures. Two different EEG microstate complexities were proposed to quantify the randomness (type I) and complexity (type II) of the EEG microstate series during the time course of the general anesthesia.

Results

The coverage and occurrence of microstate E (prefrontal pattern) and the duration of microstate B (right frontal pattern) could distinguish the states of preinduction wakefulness, unconsciousness, and recovery under both anesthetics. Type I EEG microstate complexity based on mean information gain significantly increased from awake to unconsciousness state (propofol: from mean ± SD, 1.562 ± 0.059 to 1.672 ± 0.023, P < 0.001; esketamine: 1.599 ± 0.051 to 1.687 ± 0.013, P < 0.001), and significantly decreased from unconsciousness to recovery state (propofol: 1.672 ± 0.023 to 1.537 ± 0.058, P < 0.001; esketamine: 1.687 ± 0.013 to 1.608 ± 0.028, P < 0.001) under both anesthetics. In contrast, type II EEG microstate fluctuation complexity significantly decreased in the unconscious state under both drugs (propofol: from 2.291 ± 0.771 to 0.782 ± 0.163, P < 0.001; esketamine: from 1.645 ± 0.417 to 0.647 ± 0.252, P < 0.001), and then increased in the recovery state (propofol: 0.782 ± 0.163 to 2.446 ± 0.723, P < 0.001; esketamine: 0.647 ± 0.252 to 1.459 ± 0.264, P < 0.001).

Conclusions

Both type I and type II EEG microstate complexities are drug independent. Thus, the EEG microstate complexity measures that the authors proposed are promising tools for building state-related neural correlates of consciousness to quantify anesthetic-induced unconsciousness.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Relevance of Protein Intake for Weaning in the Mechanically Ventilated Critically Ill: Analysis of a Large International Database
Authors: Hartl Wolfgang H. , Kopper Philipp , Xu Lisa , Heller Luca , Mironov Maxim , Wang Ruiyi , Day Andrew G. , Elke Gunnar , Küchenhoff Helmut , Bender Andreas
Published: December 2023

OBJECTIVES:

The association between protein intake and the need for mechanical ventilation (MV) is controversial. We aimed to investigate the associations between protein intake and outcomes in ventilated critically ill patients.

DESIGN:

Analysis of a subset of a large international point prevalence survey of nutritional practice in ICUs.

SETTING:

A total of 785 international ICUs

PATIENTS:

A total of 12,930 patients had been in the ICU for at least 96 hours and required MV by the fourth day after ICU admission at the latest.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We modeled associations between the adjusted hazard rate (aHR) of death in patients requiring MV and successful weaning (competing risks), and three categories of protein intake (low: < 0.8 g/kg/d, standard: 0.8–1.2 g/kg/d, high: > 1.2 g/kg/d). We compared five different hypothetical protein diets (an exclusively low protein intake, a standard protein intake given early (days 1–4) or late (days 5–11) after ICU admission, and an early or late high protein intake). There was no evidence that the level of protein intake was associated with time to weaning. However, compared with an exclusively low protein intake, a standard protein intake was associated with a lower hazard of death in MV: minimum aHR 0.60 (95% CI, 0.45–0.80). With an early high intake, there was a trend to a higher risk of death in patients requiring MV: maximum aHR 1.35 (95% CI, 0.99–1.85) compared with a standard diet.

CONCLUSIONS:

The duration of MV does not appear to depend on protein intake, whereas mortality in patients requiring MV may be improved by a standard protein intake. Adverse effects of a high protein intake cannot be excluded.
Child exposure to organophosphate and pyrethroid insecticides measured in urine, wristbands, and household dust and its implications for child health in South Africa: A panel study
Authors: Veludo Adriana Fernandes , Röösli Martin , Dalvie Mohamed Aqiel , Stuchlík Fišerová Petra , Prokeš Roman , Přibylová Petra , Šenk Petr , Kohoutek Jiří , Mugari Mufaro , Klánová Jana , Huss Anke , Figueiredo Daniel Martins , Mol Hans , Dias Jonatan , Degrendele Céline , Fuhrimann Samuel
Published: December 2023

Background:

Children in agricultural areas are exposed to organophosphate (OP) and pyrethroid (PYR) insecticides. This explorative study investigated child exposure to OPs and PYRs, comparing temporal and spatial exposure variability within and among urine, wristbands, and dust samples.

Methods:

During spraying season 2018, 38 South African children in two agricultural areas (Grabouw/Hex River Valley) and settings (farm/village) participated in a seven-day study. Child urine and household dust samples were collected on days 1 and 7. Children and their guardians were wearing silicone wristbands for seven days. Intraclass correlation coefficients (ICCs) evaluated temporal agreements between repeated urine and dust samples, Spearman rank correlations (Rs) evaluated the correlations among matrices, and linear mixed-effect models investigated spatial exposure predictors. A risk assessment was performed using reverse dosimetry.

Results:

Eighteen OPs/PYRs were targeted in urine, wristbands, and dust. Levels of chlorpyrifos in dust (ICC = 0.92) and diethylphosphate biomarker in urine (ICC = 0.42) showed strong and moderate temporal agreement between day 1 and day 7, respectively. Weak agreements were observed for all others. There was mostly a weak correlation among the three matrices (Rs = −0.12 to 0.35), except for chlorpyrifos in dust and its biomarker 3,5,6-trichloro-2-pyridinol in urine (Rs = 0.44). No differences in exposure levels between living locations were observed. However, 21% of the urine biomarker levels exceeded the health-risk threshold for OP exposure.

Conclusions:

Observed high short-term variability in exposure levels during spraying season highlights the need for repeated sampling. The weak correlation between the exposure matrices points to different environmental and behavioral exposure pathways. Exceeding risk thresholds for OP should be further investigated.
Risk of alcohol-associated liver disease in the offspring of parents with alcohol-associated liver disease: A nationwide cohort study
Authors: Jepsen Peter , West Joe , Kann Anna Emilie , Kraglund Frederik , Morling Joanne , Crooks Colin , Askgaard Gro
Published: December 2023

Background and Aims:

Offspring of patients with alcohol-associated liver disease (ALD) may have a higher risk of ALD. We examined their risk of ALD and survival with ALD.

Approach and Results:

We used Danish nationwide registries to identify the offspring of patients diagnosed with ALD in 1996–2018 and 20:1 matched comparators from the general population. They were followed for ALD diagnosis through 2018. We used landmark competing risk analysis to estimate the age-specific absolute and relative 10-year risks of ALD. ALD was diagnosed in 385 of 60,707 offspring and 2842 of 1,213,357 comparators during 0.7 and 14.0 million person-years of follow-up, respectively, yielding an incidence rate ratio of 2.73 (95% CI: 2.44–3.03). The risk of being diagnosed with ALD within the next 10 years peaked at age 55 years for offspring and age 57 years for comparators with 10-year risks of 1.66% (95% CI: 1.16–2.30) in offspring and 0.81% (95% CI: 0.68–0.97) in comparators at these ages. Offspring were younger at ALD diagnosis than comparators (median age of 47.4 vs. 48.9 years), yet slightly more of them had developed cirrhosis (60.3% vs. 58.7%). Survival after ALD diagnosis was similar in offspring and comparators, adjusted hazard ratio=1.03 (95% CI: 0.88–1.21), so on average offspring died younger due to their younger age at diagnosis.

Conclusions:

Offspring of patients with ALD had a low but increased risk of ALD. Screening offspring for chronic liver disease may be unnecessary, but other interventions to mitigate alcohol-associated harm should be considered.
Medication Errors in Pediatric Emergency Departments
Authors: Alsabri Mohammed , Eapen Diane , Sabesan Vaishnavi , Tarek Hassan Zeyad , Amin Mody , Elshanbary Alaa Ahmed , Alhaderi Ayman , Elshafie Emad , Al-sayaghi Khaled M.
Published: December 2023

Objective

This systematic review aims to investigate the prevalence, preventability, and severity of medication errors in pediatric emergency departments (P-EDs). It also aims to identify common types of medication errors, implicated medications, risk factors, and evaluate the effectiveness of interventions in preventing these errors.

Methods

A systematic review analyzed 6 primary studies with sample sizes ranging from 96 to 5000 pediatric patients in P-EDs. The review followed Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and included observational studies and randomized controlled trials involving patients aged 18 years and younger. Comprehensive searches in biomedical databases were conducted, and conflicts in record screening were resolved by a third reviewer using systematic review software.

Results

Medication errors in P-EDs are prevalent, ranging from 10% to 15%, with dosing errors being the most common, accounting for 39% to 49% of reported errors. These errors primarily stem from inaccurate weight estimations or dosage miscalculations. Inadequate dosing frequency and documentation also contribute significantly to medication errors. Commonly implicated medications include acetaminophen, analgesics, corticosteroids, antibiotics, bronchodilators, and intravenous fluids. Most errors are categorized as insignificant/mild (51.7% to 94.5%) or moderate (47.5%). Risk factors associated with medication errors in P-EDs include less experienced physicians, severely ill patients, and weekend/specific-hour ordering. Human factors such as noncompliance with procedures and communication failures further contribute to medication errors. Interventions such as health information technology solutions like ParentLink and electronic medical alert systems, as well as structured ordering systems, have shown promise in reducing these errors, although their effectiveness varies.

Conclusions

Overall, this systematic review provides valuable insights into the complexity of medication errors in the P-ED, emphasizes the need for targeted interventions, and offers recommendations to enhance medication safety and reduce preventable errors in this critical health care setting.
The Perceived Meaning of Traumatic Brain Injury for Older Adults: A Longitudinal-Multiple Case Study
Authors: Jung Wonkyung , Vogel Mia , Figuracion Karl Cristie F , Byun Eeeseung , Thompson Hilaire
Published: December 2023

Purpose

The aim of this study was to explore the perceived meaning of traumatic brain injury (TBI) over the first-year postinjury among older adults and to explore if and how meaning changes.

Design

A longitudinal multiple-case study design was used.

Methods

Semistructured face-to-face interviews were completed at 1 week and 1, 3, 6, and 12 months postinjury. Transcripts were analyzed using inductive thematic analysis.

Results

Fifty-five interviews were conducted with 12 participants. Four themes were identified: gratitude, vulnerability and dependence, slowing down and being more careful, and a chance for reflecting on life. Most participants’ perceptions of their TBI remained either consistently positive or negative over the first-year postinjury.

Clinical Relevance

Nurses should elicit and support patients’ positive illness perceptions regarding their brain injury, which can contribute to a higher quality of life. For those patients with negative illness perceptions, nurses should provide resources in order to support coping and resilience following brain injury.

Conclusions

This study is the first study to explore individual perceptions over time of the meaning made from experiencing TBI among older adults. Findings can serve as a foundation for tailored supportive interventions among older adults following TBI to maximize quality of life.
MEAN ARTERIAL PRESSURE/NOREPINEPHRINE EQUIVALENT DOSE INDEX AS AN EARLY MEASURE FOR MORTALITY RISK IN PATIENTS WITH SHOCK ON VASOPRESSORS
Authors: Yang Jie , Zou Xia , Wang Ruoran , Kang Yan , Ou Xiaofeng , Wang Bo
Published: December 2023

Purpose:We aimed to investigate the association between the early mean arterial pressure (MAP)/norepinephrine equivalent dose (NEQ) index and mortality risk in patients with shock on vasopressors and further identify the breakpoint value of the MAP/NEQ index for high mortality risk.Methods:Based on the Medical Information Mart for Intensive Care IV database, we conducted a retrospective cohort study involving 19,539 eligible intensive care unit records assigned to three groups (first tertile, second tertile, and third tertile) by different MAP/NEQ indexes within 24 h of intensive care unit admission. The study outcomes were 7-, 14-, 21-, and 28-day mortality. A Cox model was used to examine the risk of mortality following different MAP/NEQ indexes. The receiving operating characteristic curve was used to evaluate the predictive ability of the MAP/NEQ index. The restricted cubic spline was applied to fit the flexible correlation between the MAP/NEQ index and risk of mortality, and segmented regression was further used to identify the breakpoint value of the MAP/NEQ index for high mortality risk.Results:Multivariate Cox analysis showed that a high MAP/NEQ index was independently associated with decreased mortality risks. The areas under the receiving operating characteristic curve of the MAP/NEQ index for different mortality outcomes were nearly 0.7. The MAP/NEQ index showed an L-shaped association with mortality outcomes or mortality risks. Exploration of the breakpoint value of the MAP/NEQ index suggested that a MAP/NEQ index less than 183 might be associated with a significantly increased mortality risk.Conclusions:An early low MAP/NEQ index was indicative of poor prognosis in patients with shock on vasopressors.
Integrating Causal Discovery and Clinically-Relevant Insights to Explore Directional Relationships between Autistic Features, Sex at Birth, and Cognitive Abilities
Authors: Francis Sunday , Tseng Angela , Rawls Eric , Conelea Christine , Grissom Nicola , Kummerfeld Erich , Ma Sisi , Jacob Suma
Published: December 2023

Prevalence in autism spectrum disorder (ASD) diagnosis has long been strongly male-biased. Yet, consensus has not been reached on mechanisms and clinical features that underlie sex-based discrepancies. Whereas females may be under-diagnosed because of inconsistencies in diagnostic/ascertainment procedures (sex-biased criteria, social camouflaging), diagnosed males may have exhibited more overt behaviors (e.g., hyperactivity, aggression) that prompted clinical evaluation. Applying a novel network-theory-based approach, we extracted data-driven, clinically-relevant insights from a large, well-characterized sample (Simons Simplex Collection) of 2175 autistic males (Ages = 8.9±3.5 years) and 334 autistic females (Ages = 9.2±3.7 years). Exploratory factor analysis (EFA) and expert clinical review reduced data dimensionality to 15 factors of interest. To offset inherent confounds of an imbalanced sample, we identified a subset of males (N=331) matched to females on key variables (Age, IQ) and applied data-driven CDA using Greedy Fast Causal Inference (GFCI) for three groups (All Females, All Males, and Matched Males). Structural equation modeling (SEM) extracted measures of model fit and effect sizes for causal relationships between sex, age, and, IQ on EFA-selected factors capturing phenotypic representations of autism across sensory, social, and restricted and repetitive behavior domains. Our methodology unveiled sex-specific directional relationships to inform developmental outcomes and targeted interventions.
Assessing Sociodemographic Factors Associated with Household Hardships during the COVID-19 Pandemic in Manhiça, Mozambique using Data Collected between April 2021 and February 2022
Authors: Nhacolo Ariel Q. , Muir Jonathan A. , Madewell Zachary J. , Keiri Fatima , Sacoor Charfudin N. , Jamisse Edgar L. , Xerinda Elisio G. , Matsena Teodimiro , Hunguana Aura M. , Bassat Quique , Whitney Cynthia G. , Mandomando Inácio M. , Cunningham Solveig A.
Published: December 2023

Background

COVID-19 resulted in vast disruption to life in the 21stcentury. To quell the disease spread, national governments implemented several containment measures like state of emergency, curfews, and lockdowns that likely created hardships for households. To improve knowledge of the negative consequences of these lockdowns, we examine the extent to which the pandemic period was associated with hardships at the household level and assess factors associated with household vulnerability to these hardships.

Methods

We conducted a cross-sectional survey between April 2021 and February 2022 among households residing in the district of Manhiça through a survey questionnaire fielded in the Health and Demographic Surveillance System (HDSS) operating in Manhiça, Mozambique. Logistic regression was used to analyze associations between the head of household and household characteristics with specific household hardships (business closure, food price increase, household member detained, input inflation, job loss).

Results

Households headed by individuals with lower education and employed in non-agricultural occupations as well as households that were larger in size or poorer in asset ownership compared to other households were generally at greater risk of experiencing a larger variety of hardships. Conversely, households that owned “distance demolishing technologies” such as motorcycles were less likely to experience these hardships, presumably as they were able to transcend local conditions.

Conclusions

These results identify at-risk groups according to a social determinants of vulnerability framework and will help inform future policies and practices that aim to mitigate the negative consequences of COVID-19 as well as future disease outbreaks.
“Spectromics”: Holistic Optical Assessment of Human Cartilage via Complementary Vibrational Spectroscopy for Osteoarthritis Diagnosis
Authors: Cook Hiroki , Crisford Anna , Bourdakos Konstantinos , Dunlop Douglas , Oreffo Richard OC , Mahajan Sumeet
Published: December 2023

Osteoarthritis (OA) is the most common degenerative joint disease, presented as wearing down of articular cartilage and resulting in pain and limited mobility for 1 in 10 adults in the UK.1There is an unmet need for patient friendly paradigms for clinical assessment that do not require ionising radiation (CT), exogenous contrast enhancing dyes (MRI), biopsy, and/or instrumentation approaches (arthroscopy or endoscopy). Hence, techniques that use non-destructive, near- and shortwave infrared light (NIR, SWIR) may be ideal providing for non-invasive, label-free and deep tissue interrogation. This study demonstrates multimodal “spectromics”, low-level abstraction data fusion of non-destructive NIR Raman scattering spectroscopy and NIR-SWIR absorption spectroscopy, providing an enhanced, interpretable “fingerprint” for diagnosis of OA in human cartilage. Samples were excised from femoral heads post hip arthroplasty from OA patients (n=13) and age-matched control (osteoporosis) patients (n=14). Under multivariate statistical analysis and supervised machine learning, tissue was classified to high precision: 100% segregation of tissue classes, and a classification accuracy of 95% (control) and 80% (OA), using the combined vibrational data. There was a marked performance improvement (5 to 6-fold for multivariate analysis) using the spectromics fingerprint compared to results obtained from solely Raman or NIR-SWIR data. Furthermore, discriminatory spectral features in the enhanced fingerprint elucidated clinically relevant tissue components (OA biomarkers). In summary, spectromics provides comprehensive information for early OA detection and disease stratification, imperative for effective intervention in treating the degenerative onset disease for an aging demographic.
One LLM is not Enough: Harnessing the Power of Ensemble Learning for Medical Question Answering
Authors: Yang Han , Li Mingchen , Zhou Huixue , Xiao Yongkang , Fang Qian , Zhang Rui
Published: December 2023

Objective

To enhance the accuracy and reliability of diverse medical question-answering (QA) tasks and investigate efficient approaches deploying the Large Language Models (LLM) technologies, We developed a novel ensemble learning pipeline by utilizing state-of-the-art LLMs, focusing on improving performance on diverse medical QA datasets.

Materials and Methods

Our study employs three medical QA datasets: PubMedQA, MedQA-USMLE, and MedMCQA, each presenting unique challenges in biomedical question-answering. The proposed LLM-Synergy framework, focusing exclusively on zero-shot cases using LLMs, incorporates two primary ensemble methods. The first is a Boosting-based weighted majority vote ensemble, where decision-making is expedited and refined by assigning variable weights to different LLMs through a boosting algorithm. The second method is Cluster-based Dynamic Model Selection, which dynamically selects the most suitable LLM votes for each query, based on the characteristics of question contexts, using a clustering approach.

Results

The Majority Weighted Vote and Dynamic Model Selection methods demonstrate superior performance compared to individual LLMs across three medical QA datasets. Specifically, the accuracies are 35.84%, 96.21%, and 37.26% for MedMCQA, PubMedQA, and MedQA-USMLE, respectively, with the Majority Weighted Vote. Correspondingly, the Dynamic Model Selection yields slightly higher accuracies of 38.01%, 96.36%, and 38.13%.

Conclusion

The LLM-Synergy framework with two ensemble methods, represents a significant advancement in leveraging LLMs for medical QA tasks and provides an innovative way of efficiently utilizing the development with LLM Technologies, customing for both existing and potentially future challenge tasks in biomedical and health informatics research.
State-wise Economic Burden of Road Traffic Accidents in India
Authors: Sajith Kumar S , Bagepally Bhavani Shankara , Sasidharan Akhil , Jagadeesh Kayala Venkata , Ponniah Manickam
Published: December 2023

Introduction

Road traffic accidents (RTA) cause multifarious detrimental consequences, including fatality and serious injuries. RTAs cause considerable financial strain on healthcare systems with high costs of medical care, long-term care for the injured, and lost productivity. To assess this burden, we estimated state-wise economic costs of RTA in India. We followed CHEERS Checklist 2022 to present study’s methods and outcomes.

Methods

Data were obtained from Global Burden of Disease Injuries and Risk Factors study, Government of India’s budget documents, annual reports of National Health Authority, controller general of accounts, and Economic Surveys. Cost per disability-adjusted life years (DALY), direct costs, indirect costs and total costs associated with RTA burden were estimated for India and by its states.

Results

RTA burden declined in all Indian states except Jammu and Kashmir (with a minor increase from 1,458 to 1,564 DALYs per 100,000) and Rajasthan (from 1,275 to 1,394 DALYs per 100,000) during 2010-19 period. Estimated mean cost per DALY in India due to RTA (95%CI) was □1,821(□1,606 to □2,036) [US$ 22(19 to 24)] with a median (IQR) of □1,609(551) [US$ 19 (7)]. As of 2019, the estimated mean total cost of RTA burden in India was □1,017 billion [US$ 12 billion], with a median (IQR) of □731 billion(1,220 billion) [US$ 9 billion(15 billion)].

Conclusion

Burden of RTAs declined across the Indian States during 2010-2019, and same was not observed with fiscal implications. The study reiterates the need for strategic road safety interventions to ameliorate socio-economic and health impacts of RTAs in India.
In vivovalidation of late-onset Alzheimer’s disease genetic risk factors
Authors: Sasner Michael , Preuss Christoph , Pandey Ravi S. , Uyar Asli , Garceau Dylan , Kotredes Kevin P. , Williams Harriet , Oblak Adrian L. , Lin Peter Bor-Chian , Perkins Bridget , Soni Disha , Ingraham Cindy , Lee-Gosselin Audrey , Lamb Bruce T. , Howell Gareth R. , Carter Gregory W.
Published: December 2023

Structured Abstract

Introduction

Genome-wide association studies have identified over 70 genetic loci associated with late-onset Alzheimer’s disease (LOAD), but few candidate polymorphisms have been functionally assessed for disease relevance and mechanism of action.

Methods

Candidate genetic risk variants were informatically prioritized and individually engineered into a LOAD-sensitized mouse model that carries the AD risk variants APOE4 and Trem2*R47H. Potential disease relevance of each model was assessed by comparing brain transcriptomes measured with the Nanostring Mouse AD Panel at 4 and 12 months of age with human study cohorts.

Results

We created new models for 11 coding and loss-of-function risk variants. Transcriptomic effects from multiple genetic variants recapitulated a variety of human gene expression patterns observed in LOAD study cohorts. Specific models matched to emerging molecular LOAD subtypes.

Discussion

These results provide an initial functionalization of 11 candidate risk variants and identify potential preclinical models for testing targeted therapeutics.
Egg-laying hormone expression in identified neurons across developmental stages and reproductive states of the nudibranchBerghia stephanieae
Authors: Tait Cheyenne C. , Ramirez M. Desmond , Katz Paul S.
Published: December 2023

Neuropeptides play essential roles in coordinating reproduction. Egg-laying hormone (ELH) is conserved in genetic sequence and behavioral function across molluscs, where neuronal clusters secrete ELH to modulate and induce egg-laying. Here we investigated ELH in the nudibranch mollusc,Berghia stephanieae. ELH preprohormone gene orthologs, which showed clade-specific differences at the C-terminus of the predicted bioactive peptide, were identified in brain transcriptomes across several nudipleuran species, includingB. stephanieae. Injection of synthesizedB. stephanieaeELH peptide into mature individuals induced egg-laying. ELH gene expression in the brain and body was mapped usingin-situhybridization chain reaction. Across the adult brain, 300-400 neurons expressed ELH. Twenty-one different cell types were identified in adults, three of which were located unilaterally on the right side, which corresponds to the location of the reproductive organs. Ten cell types were present in pre-reproductive juvenile stages. An asymmetric cluster of approximately 100 small neurons appeared in the right pedal ganglion of late-stage juveniles. Additional neurons in the pleural and pedal ganglia expressed ELH only in adults that were actively laying eggs and sub-adults that were on the verge of doing so, implicating their direct role in reproduction. Outside the brain, ELH was expressed on sensory appendages, including in presumptive sensory neurons. ELH shares deep homology with the corticotropin-releasing hormone gene family, which has roles broadly in stress response. Its widespread expression in the nudibranchB. stephanieaesuggests that ELH plays a role beyond reproduction in gastropod molluscs.

Highlights

Egg-laying hormone (ELH) preprohormone sequences were identified in the transcriptomes of several nudipleuran molluscs.

Many ELH-expressing neurons and clusters in the brain could be individually identified based on soma position and morphology.

Some identified ELH-expressing neurons were not observed until later juvenile stages.

Some neurons expressed ELH in adults only when they were actively laying eggs.

Many hundreds of ELH-expressing neurons were present in peripheral appendages.