bluuebunny/crossref_metadata_2025 huggingface dataset:
Hematoxylin and Eosin Staining Helps Reduce Maternal Contamination in Short Tandem Repeat Genotyping for Hydatidiform Mole Diagnosis
Authors: Zhao Yating , Cai Luya , Zhang Xiaofei , Zhang Huifang , Cai Limeng , Zhou Lin , Huang Bo , Qian Jianhua
Published: August 2023

Short tandem repeat (STR) genotyping provides parental origin information about aneuploidy pregnancy loss and has become the current gold standard for hydatidiform moles diagnosis. STR genotyping diagnostic support most commonly relies on formalin-fixed paraffin-embedded samples, but maternal contamination is one of the most common issues based on traditional unstained sections. To evaluate the influence of hematoxylin and eosin (H&E) staining on DNA quality and STR genotyping, DNA was isolated from unstained, deparaffinized hydrated, and H&E-stained tissue sections (i.e. 3 groups) from each of 6 formalin-fixed paraffin-embedded placentas. The macrodissected view field, DNA quality, and polymerase chain reaction amplification efficiency were compared among groups. STR genotyping analysis was performed in both the testing cohort (n = 6) and the validation cohort (n = 149). H&E staining not only did not interfere with molecular DNA testing of formalin-fixed paraffin-embedded tissue but also had a clearer macrodissected field of vision. In the testing cohort, H&E-stained sections were the only group that did not exhibit maternal miscellaneous peaks in STR genotyping results. In the validation cohort, 138 (92.62%) cases yielded satisfactory amplification results without maternal contamination. Thus, H&E staining helped to reduce maternal contamination in STR genotyping for hydatidiform mole diagnosis, suggesting that H&E-stained sections can be incorporated into the hydatidiform mole molecular diagnostic workflow.
U-shaped Association between Serum Calcium Levels and 28-Day Mortality in Patients with Sepsis: A Retrospective Analysis of the MIMIC-III Database
Authors: Yan Danyang , Xie Xi , Fu Xiangjie , Pei Siya , Wang Yanjie , Deng Ying , Yao Run , Li Ning
Published: August 2023

Background

Serum calcium levels disorder have been reported to be associated with poor prognosis in different diseases. Studies on the association between serum calcium and outcomes of septic patients remained limited. The aim of this study is to investigate the association between serum calcium and 28-day mortality in septic patients.

Method

Patients diagnosed with sepsis in the Medical Information Mart for Intensive Care III database were included. Patients were divided into five groups according to the quintiles of serum calcium levels, and their baseline characteristics were compared. Multivariate Cox regression models were employed to assess the association between serum calcium and 28-day mortality. Smooth curve fitting and segmented regression models were used to visualize the association between serum calcium levels and 28-day mortality risk. The 28-day survival probability between five groups was analyzed using Kaplan-Meier curves.

Results

A total of 3016 patients with sepsis were enrolled, and the 28-day mortality rate was 35.64%. After adjusting for confounders, compared with the reference quintile (Q4: 9.00–9.50), the lowest serum calcium level quintile (Q1: 5.70–8.20) was independently associated with an increased risk of 28-day mortality (HR: 2.12, 95%CI: 1.76-2.56). Smooth spline fitting revealed a U-shaped association between serum calcium and 28-day mortality. When serum calcium was <9.0 mg/dL, 28-day mortality risk increased by 58% per unit decrease in serum calcium (HR: 0.42, 95%CI: 0.37-0.48). When serum calcium was >9.0 mg/dL, the 28-day mortality risk increased by 12% per unit increase in serum calcium (HR: 1.12, 95% CI: 1.04-1.20).

Conclusion

A U-shaped association was observed between serum calcium levels and 28-day mortality in septic patients. Lower or higher serum calcium levels were associated with increased risk of 28-day mortality in septic patients.
Pragmatic Skills in School-Age Children With Primary Language Impairment and Language-Learning Disabilities
Authors: Troia Gary A. , Hennenfent Lauren (Lo) , Shen Mei
Published: August 2023

We conducted a scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses to map the available research describing verbal pragmatic skills development and problems in school-age children with primary language impairments and children with language-learning disabilities. A total of 112 reports met inclusion criteria for our review. Many studies were published in journals focused on communication disorders between the years 2000 and 2019 and targeted K-12 children in the United States or the United Kingdom with developmental language disorder who were most often compared with age-matched typically developing peers using a group comparison research design. Over 60% of the studies had fewer than 25 participants in the target group. Nearly two thirds of study participants were boys, and most were Caucasian from middle- to upper-income families. The majority of studies used multiple outcome measures in data analyses, most often norm-referenced and researcher-designed tests, language sample analysis, and rating scales. A third of studies omitted information about outcome measure reliability and nearly all studies omitted validity data. Several studies are described in detail as examples and a summary of the major findings from the reviewed studies is presented.
The Narrative-Based Evolution of a Stakeholder-Engaged Research Team
Authors: Olness Gloria S. , Kurnal Jennifer J. , Broussard Thomas G. , Stillman Faye S. , Assaad Catalina C. , Garcia Leticia M. , Morgan Jodi M.
Published: August 2023

Millions of people worldwide have experienced abrupt and traumatic disruption in the flow of their personal life story as a result of stroke and the onset of aphasia. For each one who survives and embarks on the journey toward recovery, their unique and evolving narrative yields gems of wisdom borne of the experience. This wisdom is shared with others through interpersonal narrative exchange and engagement, which foster biographical coherence and provide sources of hope to others on the path toward a productive and fulfilling life. This case study illustrates how a biography-based approach to stakeholder-engaged research merges personal stories in three ways. First, the case illustrates how the personal and professional stories of the candidate research team members merged to form the team through networking over time. Second, the biography-based approach led the team to identify the written personal accounts of 259 people living with aphasia as the raw data set for their research, with the intended goal of mining gems of practical wisdom from these written biographical works. Third, the case illustrates how the biography-based approach draws on the personal stories of in-hospital experiences of research team members with aphasia to prospectively hone the initial research focus. Specifically, the team will tap the collective voice within the written accounts to evaluate the in-hospital experiences of people with aphasia. The ultimate goal will be to catalyze participatory action, in collaboration with transdisciplinary health care providers, to advance responsive, person-centered health care. The authors address challenges and priorities in stakeholder-engaged research team development, the importance of honing a research focus, and the identification of research dissemination venues. Oral and written accounts of life with aphasia offer a timeless and potentially rich source of wisdom that can be tapped through the process of stakeholder-engaged research.
Relations Between Pragmatic Language and Literacy-Related Skills in Omani Elementary Students
Authors: Troia Gary A. , Emam Mahmoud Mohamed
Published: August 2023

In this study of more than 1,000 typical and at-risk elementary Arabic-speaking students in Oman, we explore relationships between pragmatic (and other) language skills, literacy, cognition, and behavior and the degree to which demography impacts performance on associated tasks. We found, in most cases, that females performed better than males, students' performance improved between Grades 2 and 4 but declined in Grade 5, and at-risk students performed as well as their nonreferred peers except on a working memory task. Pragmatic competence was the best predictor of literacy proficiency, and vice versa, for both groups when controlling for other variables. Findings are discussed in the context of Omani education and the limited attention given to pragmatics in research on connections between language and literacy.
Artificial cells eavesdropping on HepG2 cells
Authors: Westensee Isabella Nymann , Städler Brigitte
Published: August 2023

Cellular communication is a fundamental feature to ensure the survival of cellular assemblies, such as multicellular tissue, via coordinated adaption to changes in their surroundings. Consequently, the development of integrated semi-synthetic systems consisting of artificial cells (ACs) and mammalian cells requires feedback-based interactions. Here, we illustrate that ACs can eavesdrop on HepG2 cells focusing on the activity of cytochrome P450 1A2 (CYP1A2), an enzyme from the cytochrome P450 enzyme family. Specifically,
d
-cysteine is sent as a signal from the ACs via the triggered reduction of disulfide bonds. Simultaneously, HepG2 cells enzymatically convert 2-cyano-6-methoxybenzothiazole into 2-cyano-6-hydroxybenzothiazole that is released in the extracellular space.
d
-Cysteine and 2-cyano-6-hydroxybenzothiazole react to form
d
-luciferin. The ACs respond to this signal by converting
d
-luciferin into luminescence due to the presence of encapsulated luciferase in the ACs. As a result, the ACs can eavesdrop on the mammalian cells to evaluate the level of hepatic CYP1A2 function.
Light-controlled growth of DNA organelles in synthetic cells
Authors: Agarwal Siddharth , Dizani Mahdi , Osmanovic Dino , Franco Elisa
Published: August 2023

Living cells regulate many of their vital functions through dynamic, membraneless compartments that phase separate (condense) in response to different types of stimuli. In synthetic cells, responsive condensates could similarly play a crucial role in sustaining their operations. Here we use DNA nanotechnology to design and characterize artificial condensates that respond to light. These condensates form via the programmable interactions of star-shaped DNA subunits (nanostars), which are engineered to include photo-responsive protection domains. In the absence of UV irradiation, the nanostar interactions are not conducive to the formation of condensates. UV irradiation cleaves the protection domains, increases the nanostar valency and enables condensation. We demonstrate that this approach makes it possible to tune precisely the kinetics of condensate formation by dosing UV exposure time. Our experimental observations are complemented by a computational model that characterizes phase transitions of mixtures of particles of different valency, under changes in the mixture composition and bond interaction energy. In addition, we illustrate how UV activation is a useful tool to control the formation and size of DNA condensates in emulsion droplets, as a prototype organelle in a synthetic cell. This research expands our capacity to remotely control the dynamics of DNA-based components via physical stimuli and is particularly relevant to the development of minimal artificial cells and responsive biomaterials.
Case report: isolation of Hydrogenophaga from septic blood culture following near-death drowning in lakewater
Authors: Feichtinger Stuart , Lazar Angela A. , Luebbe Megan A. , Accola Molly A. , Jung-Hynes Brittney D. , Anderson Patti J. , Koglin Kelly M. , Schliesman Karen S. , Ehlenbach William , Smith Jeannina , Chen Derrick J. , Rehrauer William M. , Bailey Adam L.
Published: August 2023

A patient suffered a non-fatal wet drowning in a freshwater lake and developed bacteremia several days later. Blood culture grew a Gram-negative rod that could not be identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). 16S ribosomal RNA sequencing of the isolate identified the microbe as Hydrogenophaga laconesensis––an environmental microbe commonly found in freshwater. The recovery of multiple pathogenic microorganisms (although not H. laconesensis) from culture of respiratory specimens prompted the initiation of antibiotic therapy with cefepime and, later, vancomycin. The patient’s clinical course gradually improved over the course of two weeks and she was ultimately discharged home with minimal sequelae. To our knowledge, this is the first evidence of human infection with bacteria in the Hydrogenophaga genus. Hydrogenophaga may be considered in cases of freshwater near-drowning, and MALDI-TOF MS databases should be updated to include H.laconesensis.
A glimpse into the dark – the bacterial and archaeal diversity of tropical anchialine cave sediments
Authors: Meland Kenneth , Iliffe Thomas M. , Thiele Stefan
Published: August 2023

Using ion torrent sequencing of the V4 region of the 16S rRNA gene, we investigated the sediment from four anchialine caves on Eleuthera (Bahamas). Anchialine caves are secluded, landlocked marine ecosystems, with high degrees of endemism. In the cave sediments, the bacterial and archaeal communities differ from marine communities and between caves, while often resembling those from low oxygen or anaerobic marine sediments. The waters of all caves investigated here were mostly saline and oxygenated, with Windermere Abyss differing from the other caves. This was mirrored by the bacterial and archaeal communities, with members of the wb1-A12 clade,

Nitrosopumilaceae

, members of the NB1-j phylum, and

Actinomarinales

being dominant in Preacher’s Blue Hole, Valentine’s Cave, and Bung Hole while

Desulfatiglans

, Bathyarchaeia, and members of the GIF3 and Sva0485 clades were dominant in Windermere Abyss. All communities showed taxa found in oxygenated and anoxic sediments, thus indicating a variety of chemoautotrophic lifestyles, including methane-, nitrogen- and sulphur cycling. The communities were different from other caves and included understudied or otherwise rare taxa, partially from deep sea sediments, implying that the isolation might be an evolutionary factor, and indicating that anchialine caves could be a window into the deep sea.
Lack of detection of SARS-CoV-2 in Wildlife from Kerala, India in 2020-21
Authors: Zachariah Arun , Krishnankutty Sajesh P , Manazhi Jishnu , Omanakuttan Vishnu , Santosh Sam , Blanchard Adam , Tarlinton Rachael
Published: August 2023

Spill over of SARs-CoV-2 into a variety of wild and domestic animals has been an ongoing feature of the human pandemic. The establishment of a new reservoir in white tailed deer in North America and increasing divergence of the viruses circulating in them from those circulating in the human population has highlighted the ongoing risk this poses for global health. Some parts of the world have seen more intensive monitoring of wildlife species for SARS-CoV-2 and related coronaviruses but there are still very large gaps in geographical and species-specific information. This paper reports negative results for SARS-CoV-2 PCR based testing using a pan coronavirus end point RDRP PCR and a Sarbecovirus specific E gene qPCR on lung and or gut tissue from wildlife from the Indian State of Kerala. These animals included: 121 Rhinolophus rouxii (Rufous Horsehoe Bat), 6 Rhinolophus bedommei (Lesser Woolly Horseshoe Bat), 15 Rossettus leschenaultii (Fulvous Fruit Bat), 47 Macaca radiata (Bonnet macaques), 35 Paradoxurus hermaphroditus (Common Palm Civet), 5 Viverricula indica (Small Indian Civet) , 4 Herpestes edwardsii (Common Mongoose), 10 Panthera tigris (Bengal Tiger), 8 Panthera pardus fusca ( Indian Leopard), 4 Prionailurus bengalensis (Leopard cats), 2  Felis chaus (Jungle cats), 2 Cuon alpinus (Wild dogs)  and 1 Melursus ursinus (sloth bear).
Fatal disseminated Cryptococcosis with diverse risk factors: A Case series from a tertiary care hospital in eastern India
Authors: Halim Isra , Jha Sweta , Kokkayil Prathyusha , Kirti Ravi , Bhushan Divendu , Sarfraz Asim , Pati Binod Kumar , Thakuria Bhaskar
Published: August 2023

Background: Cryptococcos noeformans is a ubiquitous fungal infection that can cause life threatening meningitis and fungemia in both immunocompromised and immunocompetent host. Disseminated cryptococcosis is often a retrospective diagnosis when blood cultures are found positive for Cryptococcus species.
Case presentation: We report two cases of Disseminated cryptococcosis with different risk factors emphasizing on early clinical suspicion, diagnosis and treatment.
First case was of non- alcoholic steatohepatitis patient who presented with complain of abdominal swelling and hemiparesis. Other case was of retro positive male presenting with complains of headache and fever. These patients underwent empirical antibacterial and anti-tubercular therapy which was ineffective. Finally, diagnosis was made on the basis of India ink stain, Gram stain and fungal culture which were confirmed by polymerase chain reaction and gene sequencing of both the isolates. But the patients could not be saved due to delay in diagnosis.
Conclusion: Disseminated cryptococcosis is an advanced potentially fatal disease. Cryptococcosis should be suspected not only in cases of HIV or transplant patients but also in cases of chronic liver diseases.  An early clinical suspicion would help recognize these cases sooner. The microbiologist should always have a keen eye and an equally high index of suspicion especially in the presence of capsulated round yeast cells in any sample of sick patients. Early diagnosis and treatment are imperative to prevent mortality.
A novel quantification method for RPE phagocytosis using a VLC-PUFA-based strategy
Authors: Gao Fangyuan , Tom Emily , Lieffrig Stephanie A. , Finnemann Silvia C. , Skowronska-Krawczyk Dorota
Published: August 2023

The vertebrate retinal pigment epithelium (RPE) lies adjacent to the photoreceptors and is responsible for the engulfment and degradation of shed photoreceptor outer segment fragments (POS) through receptor-mediated phagocytosis. Phagocytosis of POS is critical for maintaining photoreceptor function and is a key indicator of RPE functionality. Popular established methods to assess RPE phagocytosis rely mainly on quantifying POS proteins, especially their most abundant protein rhodopsin, or on fluorescent dye conjugation of bulk, unspecified POS components. While these approaches are practical and quantitative, they fail to assess the fate of POS lipids, which make up about 50% of POS by weight and whose processing is essential for life-long functionality of RPE and retina. Here, we have developed a novel VLC-PUFA-based approach for evaluating RPE phagocytic activity by primary bovine and rat RPE and the human ARPE-19 cell line and validated its results using traditional methods. This new approach can be used to detect the dynamic process of phagocytosis at varying POS concentrations and incubation times and offers a robust, unbiased, and reproducible assay that will have utility in studies of POS lipid processing.
Estimating epidemic dynamics with genomic and time series data
Authors: Zarebski Alexander E. , Zwaans Antoine , Gutierrez Bernardo , du Plessis Louis , Pybus Oliver G.
Published: August 2023

Accurately estimating the prevalence and transmissibility of an infectious disease is an important task in genetic infectious disease epidemiology. However, generating accurate estimates of these quantities, that are informed by both epidemic time series and pathogen genome sequence data, is a challenging problem. While birth-death processes and coalescent-based models are popular methods for modelling the transmission of infectious diseases, they both struggle (for different reasons) with estimating the prevalence of infection.

Here we extended our approximate likelihood, which combines phylogenetic information from sampled pathogen genomes and epidemiological information from a time series of case counts, to estimate historical prevalence (in addition to the effective reproduction number). We implement this new method in a BEAST2 package called Timtam. In a simulation study our approximation is well-calibrated and can recover the parameters of simulated data.

To demonstrate how Timtam can be applied to real data sets we carried out empirical analyses of data from two infectious disease outbreaks: the outbreak of SARS-CoV-2 onboard the Diamond Princess cruise ship in early 2020 and poliomyelitis in Tajikistan in 2010. In both cases we recover estimates consistent with previous analyses.
Predictors of Affective and Cognitive Alterations in Minor Stroke Patients: clinical, omics, neuropsychological and radiological signatures
Authors: Pereira Cristina , Mauri Gerard , Vázquez-Justes Daniel , Mitjana Raquel , Piñol Gerard , Arqué Gloria , Purroy Francisco
Published: August 2023

Background. Despite the mild severity of initial symptoms, minor stroke (MS) is a common clinical condition that can be associated with significant affective and cognitive alterations. Methods. The PSICOICTUS project aimed to investigate the predictors of these alterations in a cohort of 118 consecutive MS patient. This observational, longitudinal, and prospective study included comprehensive evaluation at baseline (within the first five days of symptom onset) and follow-ups at 15 days, 6 months, and 12 months. A screening battery consisting of the Montreal Cognitive Assessment (MoCA), Montgomery-Åsberg Depression Rating Scale (MADRS), and Apathy Evaluation Scale-Clinician version (AES-c) was used to identify patients with affective and/or cognitive alterations. Results. Cognitive alterations were further assessed using a comprehensive neuropsychological battery. Screening tests revelated that 17.0% of patients had affective alterations, 9.3% had cognitive alterations, and 14.4% presented with both affective and cognitive alterations. Among patients with cognitive alterations, executive functions, attention and processing speed were found to be the most affected domains. The study also concluded a biomarker discovery analysis involving MRI-based neuroimaging and untargeted metabolomics/lipidomics analysis. Several predictors of affective and cognitive alterations were identified. A history of previous depressions, lower levels of Isoleucyl-Isoleucine, and PC (38:4) were associated with affective alterations. On the other hand, age above 70, the presence of a middle cerebral artery ischemic lesion, higher creatinine levels, lower triglyceride levels, and higher concentrations of 2-hydroxyhexadecanoylcarnitine were predictive of cognitive alterations. Female sex, previous history of depressive syndrome, and a higher number of chronic strokes were identified as predictors for both affective and cognitive alterations. Conclusions. These findings highlight the importance of considering affective and cognitive alterations in the management of patients with MS. The identification of specific predictors would improve the development of a differential management approach tailored to the needs of MS patients.
Chronic Pain and Eye Movements: A NeuroIS Approach to Designing Smart Clinical Decision Support Systems
Authors: Alrefaei Doaa , Djamasbi Soussan , Strong Diane
Published: August 2023

The pressing need for objective measures in the evaluation of chronic pain both in research and practice highlights the role that neuro information systems (NeuorIS) research plays in designing smart clinical decision support systems. A first step in such a research agenda is identifying practical stimuli-task paradigms that can reliably detect chronic pain from physiological measures such as eye movements. In this study, we propose and test a new stimuli-task paradigm. Our results show that our proposed stimuli-task paradigm can detect differences in information processing behavior of people with and without chronic pain. The results also show that our proposed stimuli-task paradigm can reliably predict a person’s reported subjective pain experience from his/her eye movements. These findings provide support for our proposed stimuli-task paradigm. They also show that the eye-tracking variables that we selected to test our proposed paradigm are effective in capturing the impact of chronic pain on visual attention and suggest that eye movements have the potential to serve as reliable biomarkers of chronic pain. In other words, our results provide support for the potential of eye movements to facilitate the development of smart information systems that can detect the presence and/or the severity of chronic pain from an individual’s ocular behavior.
Diagnostic efficacy of leukocyte esterase dipstick in diagnosing spontaneous bacterial peritonitis among cirrhotic patients in tertiary hospitals, Dodoma, Tanzania
Authors: Mwinyi Salum Ali , Sindato Emmanuel
Published: August 2023

Background

Spontaneous bacterial peritonitis (SBP) is complications of end stage liver disease, it associated with morbidity and mortality, the gold standard for diagnosing SBP is an ascitic fluid Polymorphonuclear neutrophil count (PMN) of ≥ 250 cells/mm3, this examination is time consuming and costly. Urine reagent dipstick detecting leukocyte esterase activity has been suggested as quick and affordable substitute. The purpose of this study was to evaluate the CYBOW™ 10 strip’s ability to diagnose SBP.

Methods

A Crossectional analytical study was conducted from November 2022 to June 2023. 224 patients with confirmed cirrhotic ascites, aged ≥ 18 years and met inclusion criteria were recruited in the study. By following sterile procedure ascitic fluid was collected, bedside ascitic fluid examination by CYBOW™ 10 reagent strips, and the samples for cytological examination were taken. Ascitic fluid with PMN ≥ 250cells/mm3was considered positive for SBP, and +1 to +3 of CYBOW™ 10 reagent strip, was used as cut off levels for a positive SBP. By using SPSS version 25, 2 by 2 table was applied to determine the sensitivity (Sn), Specificity (Sp), Positive Predictive value (PPV), and Negative Predictive Value (NPV), and Receiver Operating Characteristic (ROC) was applied to determine the area under the curve of the leukocyte esterase dipstick.

Results

On the basis of the ascitic fluid PMN count, 42 (18.75%) individuals had SBP. At cut-off point of +2 CYBOW™ 10 urine reagent strip had Sensitivity of 82.14%, Specificity of 99.39%, PPV of 95.83% and NPV of 96.79%, with AUC of 0.9074.

Conclusion

CYBOW™ 10 reagent strip test might be a helpful tool for doctors, when a rapid cell count for SBP diagnosis is not available. These strips are readily available and inexpensive, can be very helpful in areas with low resources and to patients who are unable to pay for cytology.
Long COVID in a highly vaccinated population infected during a SARS-CoV-2 Omicron wave – Australia, 2022
Authors: Woldegiorgis Mulu , Cadby Gemma , Ngeh Sera , Korda Rosemary , Armstrong Paul , Maticevic Jelena , Knight Paul , Jardine Andrew , Bloomfield Lauren , Effler Paul
Published: August 2023

Objective

To characterise Long COVID in a highly vaccinated population infected by Omicron.

Design

Follow-up survey of persons testing positive for SARS-CoV-2 in Western Australia, 16 July-3 August 2022.

Setting

Community

Participants

22,744 persons with COVID-19 who had agreed to participate in research at the time of diagnosis were texted a survey link 90 days later; non-responders were telephoned. Post stratification weights were applied to responses from 11,697 (51.4%) participants, 94.0% of whom had received >= 3 vaccine doses.

Main outcome measures

Prevalence of ‘Long COVID’ - defined as reporting new or ongoing COVID-19 illness-related symptoms or health issues 90 days post diagnosis; associated health care utilisation, reductions in work/study and risk factors were assessed using log-binomial regression.

Results

18.2% (n=2,130) of respondents met case definition for Long COVID. Female sex, being 50-69 years of age, pre-existing health issues, residing in a rural or remote area, and receiving fewer vaccine doses were significant independent predictors of Long COVID (p < 0.05). Persons with Long COVID reported a median of 6 symptoms, most commonly fatigue (70.6%) and difficulty concentrating (59.6%); 38.2% consulted a GP and 1.6% reported hospitalisation in the month prior to the survey due to ongoing symptoms. Of 1,778 respondents with Long COVID who were working/studying before their COVID-19 diagnosis, 17.9% reported reducing/discontinuing work/study.

Conclusion

90 days post Omicron infection, almost 1 in 5 respondents reported Long COVID symptoms; 1 in 15 of all persons with COVID-19 sought healthcare for associated health concerns >=2 months after the acute illness.

Significance of the study

The known

The prevalence of Long COVID varies widely across studies conducted in diverse settings globally (range: 9%-81%).

The new

In a highly vaccinated population (94% with >=3 vaccine doses), almost 20% of persons infected with the SARS-CoV-2 Omicron variant reported symptoms consistent with Long COVID 90 days post diagnosis. Long COVID was associated with sustained negative impacts on work/study and a substantial utilisation of GP services 2-3 months after the acute illness; however, ED presentations and hospitalisations for Long COVID were rare.

The implications

GP clinics play a significant role in managing the burden of Long COVID in Australia.
In severe first episode major depressive disorder, psychosomatic, chronic fatigue syndrome, and fibromyalgia symptoms are driven by immune activation and increased immune-associated neurotoxicity
Authors: Maes Michael , Almulla Abbas F , Zhou Bo , Abo Algon Ali Abbas , Sodsai Pimpayao
Published: August 2023

Background

Major depressive disorder (MDD) is accompanied by activated neuro-immune pathways, increased physiosomatic and chronic fatigue-fibromyalgia (FF) symptoms. The most severe MDD phenotype, namely major dysmood disorder (MDMD), is associated with adverse childhood experiences (ACEs) and negative life events (NLEs) which induce cytokines/chemokines/growth factors.

Aims

To delineate the impact of ACE+NLEs on physiosomatic and FF symptoms in first episode (FE)-MDMD, and examine whether these effects are mediated by immune profiles.

Methods

ACEs, NLEs, physiosomatic and FF symptoms, and 48 cytokines/chemokines/growth factors were measured in 64 FE-MDMD patients and 32 normal controls.

Results

Physiosomatic, FF and gastro-intestinal symptoms belong to the same factor as depression, anxiety, melancholia, and insomnia. The first factor extracted from these seven domains is labeled the physio-affective phenome of depression. A part (59.0%) of the variance in physiosomatic symptoms is explained by the independent effects of interleukin (IL)-16 and IL-8 (positively), CCL3 and IL-1 receptor antagonist (inversely correlated). A part (46.5%) of the variance in physiosomatic (59.0%) symptoms is explained by the independent effects of interleukin (IL)-16, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (positively) and combined activities of negative immunoregulatory cytokines (inversely associated). Partial Least Squares analysis shows that ACE+NLEs exert a substantial influence on the physio-affective phenome which are partly mediated by an immune network composed of IL-16, CCL27, TRAIL, macrophage-colony stimulating factor, and stem cell growth factor.

Conclusions

The physiosomatic and FF symptoms of FE-MDMD are partly caused by immune-associated neurotoxicity due to T helper (Th)-1 polarization, Th-1, and M1 macrophage activation and relative lowered compensatory immunoregulatory protection.
Predicting Clinical Outcomes of SARS-CoV-2 Infection During the Omicron Wave Using Machine Learning
Authors: Cogill Steven , Nallamshetty Shriram , Fullenkamp Natalie , Heberer Kent , Lynch Julie , Lee Kyung Min , Aslan Mihaela , Shih Mei-Chiung , Lee Jennifer S
Published: August 2023

The Omicron SARS-CoV-2 variant continues to strain healthcare systems. Developing tools that facilitate the identification of patients at highest risk of adverse outcomes is a priority. The study objectives are to develop population-scale predictive models that: 1) identify predictors of adverse outcomes with Omicron surge SARS-CoV-2 infections, and 2) predict the impact of prioritized vaccination of high-risk groups for said outcome. We prepared a retrospective longitudinal observational study of a national cohort of 192,984 patients in the U.S. Veteran Health Administration who tested positive for SARS-CoV-2 from January 15 to August 15, 2022. We utilized sociodemographic characteristics, comorbidities, vaccination status, and prior COVID-19 infections, at time of testing positive for SARS-CoV-2 to predict hospitalization, escalation of care (high-flow oxygen, mechanical ventilation, vasopressor use, dialysis, or extracorporeal membrane oxygenation), and death within 30 days. Machine learning models demonstrated that advanced age, high comorbidity burden, lower body mass index, unvaccinated status, prior SARS-CoV-2 infection, and oral anticoagulant use were the important predictors of hospitalization and escalation of care. Similar factors predicted death. However, prior SARS-CoV-2 infection was associated with lower 30-day mortality, and anticoagulant use did not predict mortality risk. The all-cause death model showed the highest discrimination (Area Under the Curve (AUC) = 0.895, 95% Confidence Interval (CI): 0.885, 0.906) followed by hospitalization (AUC = 0.829, CI: 0.825, 0.834), then escalation of care (AUC=0.805, CI: 0.795, 0.814). Assuming a vaccine efficacy range of 70.8 to 78.7%, our simulations projected that targeted prevention in the highest risk group may have reduced 30-day hospitalization, care escalation, and death in more than 2 of 5 unvaccinated patients.
New-onset infective endocarditis in diabetic patients receiving SGLT2I, DPP4I and GLP1a: A population-based cohort study
Authors: Chou Oscar Hou-In , Gao Tianyu , Chung Cheuk To , Jing Fengshi , Chan Jeffrey Shi Kai , Satti Danish Iltaf , Pang Ronald TK , Lee Sharen , Wong Wing Tak , Liu Tong , Lip Gregory Y H , Cheung Bernard Man Yung , Tse Gary , Zhou Jiandong
Published: August 2023

Background

Sodium-glucose cotransporter-2 inhibitors (SGLT2I) have been suggested to have beneficial effects against infection. However, the comparative risks of new onset infective endocarditis between SGLT2Is, dipeptidyl peptidase-4 inhibitors (DPP4Is) and glucagon-like peptide-1 receptor agonist (GLP1a) remain unknown.

Objective

This real-world study aims to compare the risks of infective endocarditis upon exposure to SGLT2I and dipeptidyl peptidase-4 inhibitors (DPP4I).

Methods

This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus (T2DM) on either SGLT2I or DPP4I between 1st January 2015 and 31st December 2020 using a territory-wide registry in Hong Kong. The primary outcome was new-onset infective endocarditis. The secondary outcome was cardiovascular-related mortality. Propensity score matching (1:1 ratio) using the nearest neighbour search was performed. Multivariable Cox regression was applied to identify significant associations. A three-arm sensitivity analysis including the GLP1a cohort was conducted.

Results

This cohort included 75638 T2DM patients (median age: 62.3 years old [SD: 12.8]; 55.79 % males). The SGLT2I and DPP4I groups consisted of 28774 patients and 46864 patients, respectively. After matching, 104 and 161 infective endocarditis in the SGLT2I and DPP4I groups occurred over a follow-up of 5.6 years. SGLT2I use was associated with lower risks of infective endocarditis (Hazard ratio [HR]: 0.58; 95% Confidence Interval [CI]: 0.41-0.81) and cardiovascular mortality (HR: 0.49; 95% CI: 0.33-0.72) compared to DPP4I use after adjustments for demographics, comorbidities, medications, renal function, and HbA1c levels. Similar associations were observed in subgroup analyses regardless of gender, hypertension, prior valvular disease, renal disease, or immunodeficiency. In the sensitivity analysis, SGLT2I was not associated with lower risks of infective endocarditis compared to GLP1a. The results remained consistent in the competing risk and the other sensitivity analyses.

Conclusions

SGLT2I use was associated with lower risks of new-onset infective endocarditis compared to DPP4I after adjustments.

Illustrated abstract
Assessing the performance of GPT-4 in the filed of osteoarthritis and orthopaedic case consultation
Authors: Li Juntan , Gao Xiang , Dou Tianxu , Gao Yuyang , Zhu Wannan
Published: August 2023

Background

Large Language Models (LLMs) like GPT-4 demonstrate potential applications in diverse areas, including healthcare and patient education. This study evaluates GPT-4’s competency against osteoarthritis (OA) treatment guidelines from the United States and China and assesses its ability in diagnosing and treating orthopedic diseases.

Methods

Data sources included OA management guidelines and orthopedic examination case questions. Queries were directed to GPT-4 based on these resources, and its responses were compared with the established guidelines and cases. The accuracy and completeness of GPT-4’s responses were evaluated using Likert scales, while case inquiries were stratified into four tiers of correctness and completeness.

Results

GPT-4 exhibited strong performance in providing accurate and complete responses to OA management recommendations from both the American and Chinese guidelines, with high Likert scale scores for accuracy and completeness. It demonstrated proficiency in handling clinical cases, making accurate diagnoses, suggesting appropriate tests, and proposing treatment plans. Few errors were noted in specific complex cases.

Conclusions

GPT-4 exhibits potential as an auxiliary tool in orthopedic clinical practice and patient education, demonstrating high accuracy and completeness in interpreting OA treatment guidelines and analyzing clinical cases. Further validation of its capabilities in real-world clinical scenarios is needed.
Longitudinal enlargement of choroid plexus is associated with inflammation and neurodegeneration in RRMS patients
Authors: Klistorner Samuel , Klistorner Alexander
Published: August 2023

Background

The Choroid Plexus (CP) plays a potential role in the initiation and propagation of neuroinflammatory processes in MS. However, the progressive change of the CP and its associations with biomarkers of acute and chronic inflammation, along with MS-related brain structure atrophy, have not been investigated.

Objective

This study aims to explore the longitudinal dynamics of the CP in RRMS patients and assess its relationship with inflammation and with atrophy in various brain compartments.

Methods

57 RRMS patients were examined annually for a minimum of 60 months using following MRI protocols: pre- and post-contrast (gadolinium) Sagittal 3D T1, FLAIR CUBE, diffusion weighted MRI. CP was manually segmented at baseline and last follow-up and normalised by head size. Annually lesion segmentation was performed by iQ-MSTM software suite and brain was segmented using AssemblyNet.

Results

Over the study period, the volume of CP increased by an average of 1.4% annually. The magnitude of CP enlargement significantly correlated with central brain atrophy, and to a lesser extent, total brain atrophy, white matter, and deep grey matter atrophy. Furthermore, progressive CP enlargement was significantly associated with the volume and severity of chronic lesion expansion (r=0.66, p<0.001), but not with the number or volume of new lesions.

Conclusion

Our findings indicate that ongoing inflammatory activity in the CP is linked to low-grade demyelination at the rim of chronic lesions and associated neurodegeneration of periventricular white and grey matter.
Sexual exposures associated with mpox infection: California, November 2022 to June 2023
Authors: Snyder Robert E. , Saadeh Kayla , Tang Eric C. , Johnson Kelly A. , Holland Samuel N. , Quint Joshua , Burghardt Nicole O. , Chai Shua J. , Fernando Roshani , Gonzalez Barrera Kimberly , Hernandez Cindy , McManus Korie , Lorenz Kieran , Maycott Jarett , McGinley John , Lewnard Joseph A.
Published: August 2023

Background

Exposures associated with mpox infection remain imperfectly understood.

Methods

We conducted a case-control study enrolling participants who received molecular tests for mpox/orthopoxvirus in California from November 2022 through June 2023. We collected data on behaviors during a 21-day risk period before symptom onset or testing among mpox cases and test-negative controls.

Results

Thirteen of 54 (24.1%) cases and 5/117 (4.3%) controls reported sexual exposure to individuals they identified as potential mpox cases (“index contacts”; odds ratio [OR]=7.7 [95% confidence interval: 2.5-19.3]). Among these participants, 10/13 (76.9%) cases and 2/5 (40.0%) controls reported their index contacts were not experiencing symptoms visible to participants during sex (OR=14.9 [3.6-101.8]). Only 3/54 cases (5.6%) recalled exposure to symptomatic index contacts. Cases reported greater numbers of anal/vaginal sex partners than controls (adjusted OR=2.2 [1.0-4.8] for 2-3 partners and 3.8 [1.7-8.8] for ≥4 partners). Male cases with penile lesions more commonly reported insertive anal/vaginal sex than those without penile lesions (adjusted OR=9.3 [1.6-54.8]). Cases with anorectal lesions more commonly reported receptive anal sex than cases without anorectal lesions (adjusted OR=14.4 [1.0-207.3]).

Conclusions

Sexual exposure to contacts known or suspected to have experienced mpox was associated with increased risk of infection, often when index contacts lacked apparent symptoms. Exposure to greater numbers of sex partners, including those whom participants did not identify as index contacts, was associated with increased risk of infection in a site-specific manner. While participants’ assessment of symptoms in partners may be imperfect, these findings suggest individuals without visibly prominent mpox symptoms transmit infection.
Systematic discovery of protein interaction interfaces using AlphaFold and experimental validation
Authors: Lee Chop Yan , Hubrich Dalmira , Varga Julia K. , Schäfer Christian , Welzel Mareen , Schumbera Eric , Đokić Milena , Strom Joelle M. , Schönfeld Jonas , Geist Johanna L. , Polat Feyza , Gibson Toby J. , Keller Valsecchi Claudia Isabelle , Kumar Manjeet , Schueler-Furman Ora , Luck Katja
Published: August 2023

Structural resolution of protein interactions enables mechanistic and functional studies as well as interpretation of disease variants. However, structural data is still missing for most protein interactions because we lack computational and experimental tools at scale. We thoroughly assessed AlphaFold-Multimer accuracy for structure prediction of interactions involving folded domains binding to short linear motifs from the ELM database. The structure predictions were highly sensitive but not very specific when using small protein fragments. Sensitivity decreased substantially when using long protein fragments or full length proteins with intrinsically disordered regions. We delineated a fragmentation strategy to optimize sensitivity and applied it to interactions between proteins associated with neurodevelopmental disorders. This enabled prediction of highly confident and likely disease-related novel interfaces, but also resulted in many high scoring false positive predictions. Experiments supported predicted interfaces between CREBZF-HCFC1, FBXO23-STX1B, STX1B-VAMP2, ESRRG-PSMC5, PEX3-PEX19, PEX3-PEX16, and SNRPB-GIGYF1 providing novel molecular insights for diverse biological processes. Our work highlights exciting perspectives, but also reveals clear limitations and the need for future developments to maximize the power of Alphafold-Multimer for interface predictions.
Learning interventions and training methods in health emergencies: A scoping review
Authors: Utunen Heini , Balaciano Giselle , Arabi Elham , Tokar Anna , Noyes Jane
Published: August 2023

Background

Keeping the health workforce and the public informed with the latest evolving knowledge is critical to preventing, detecting and responding to infectious disease outbreaks or other health emergencies. Having a well informed, ready, willing, and skilled workforce and an informed public can help save lives, reduce diseases and suffering, and minimize socio-economic loss in affected communities and countries. Providing support and opportunities for learning in health emergencies is much needed for capacity building. In this paper, ‘learning intervention’ refers to the provision of ad-hoc, focused, or personalized training sessions with the goal of preparing the health workers for emergencies or filling specific knowledge or skill gaps. We refer to ‘training methods’ as instructional design strategies used to teach someone the necessary knowledge and skills to perform a task.

Methods

We conducted a scoping review to map and better understand what learning interventions and training methods have been used in the different types of health emergencies and with whom. Studies were identified by searching Pubmed/Medline, Embase and consulting with experts.

Results

Of the 319 records that were included, contexts related to COVID-19, disasters in general, Ebola and wars were most frequently covered. Four topic areas were identified: Knowledge acquisition, Emergency Plans, Impact of the learning intervention, and training methods. Much of the evidence was based on observational methods with few trials, which likely reflects the unique context of each health emergency. Evolution of methods was apparent, particularly in virtual learning. Learning during health emergencies appeared to improve knowledge, management, quality of life, satisfaction and clinical outcomes.

Conclusion

This is the first scoping review to map the evidence, which serves as a first step to develop urgently needed global guidance to further improve the quality and reach of learning interventions and training methods in this context.
Identification of host endotypes using peripheral blood transcriptomics in a prospective cohort of patients with endocarditis
Authors: Duarte-Herrera Israel David , López-Martínez Cecilia , Rodríguez-García Raquel , Parra Diego , Martín-Vicente Paula , Exojo-Ramirez Sara M. , Miravete-Lagunes Karla , Iglesias Lisardo , González-Iglesias Marcelino , Fernández-Rodríguez Margarita , Carretero-Ledesma Marta , López-Alonso Inés , Gómez Juan , Coto Eliecer , Fernández Javier , Amado-Rodríguez Laura , Albaiceta Guillermo M
Published: August 2023

Objectives

To identify endotypes in patients with infective endocarditis.

Methods

Thirty-two consecutive patients with infective endocarditis were studied. Clinical data and a blood sample were collected at diagnosis, and RNA sequenced. Gene expression was used to identify two clusters, termed endocarditis endotypes (EE) 1 and 2. RNA sequencing was repeated after surgery. Transcriptionally active cell populations were identified by deconvolution. Differences between endotypes in clinical data, survival, gene expression and molecular pathways involved were assessed.

Results

18 and 14 patients were assigned to EE1 and EE2 respectively, with no differences in clinical data. Patients assigned to EE2 showed an enrichment in genes related to T-cell maturation and a decrease in the activation of the STAT pathway, with higher counts of active T-cells and lower counts of neutrophils. Fourteen patients (9 in EE1 and 5 in EE2) were submitted to surgery. Surgery in EE2 patients shifted gene expression towards a EE1-like profile. In-hospital mortality was higher in EE1 (56% vs 14%, p=0.027) with a hazard ratio of 12.987 (95% confidence interval 3.356 – 50] after adjustment by age and sex.

Conclusions

Gene expression reveals two endotypes in patients with acute endocarditis, with different underlying pathogenetic mechanisms, response to surgery and outcome.