bluuebunny/crossref_metadata_2025 huggingface dataset:
School-level intra-cluster correlation coefficients and autocorrelations for children’s accelerometer-measured physical activity in England by age and gender
Authors: Salway Ruth , Jago Russell , de Vocht Frank , House Danielle , Porter Alice , Walker Robert , Kipping Ruth , Owen Christopher G. , Hudda Mohammed T. , Northstone Kate , van Sluijs Esther ,   International Children’s Accelerometry Database (ICAD) Collaborators, Atkin Andrew , Ekelund Ulf , Esliger Dale , Hansen Bjorge H. , Sherar Lauren , van Sluijs Esther
Published: August 2024

Background

Randomised, cluster-based study designs in schools are commonly used to evaluate children’s physical activity interventions. Sample size estimation relies on accurate estimation of the intra-cluster correlation coefficient (ICC), but published estimates, especially using accelerometry-measured physical activity, are few and vary depending on physical activity outcome and participant age. Less commonly-used cluster-based designs, such as stepped wedge designs, also need to account for correlations over time, e.g. cluster autocorrelation (CAC) and individual autocorrelation (IAC), but no estimates are currently available. This paper estimates the school-level ICC, CAC and IAC for England children’s accelerometer-measured physical activity outcomes by age group and gender, to inform the design of future school-based cluster trials.

Methods

Data were pooled from seven large English datasets of accelerometer-measured physical activity data between 2002–18 (> 13,500 pupils, 540 primary and secondary schools). Linear mixed effect models estimated ICCs for weekday and whole week for minutes spent in moderate-to-vigorous physical activity (MVPA) and being sedentary for different age groups, stratified by gender. The CAC (1,252 schools) and IAC (34,923 pupils) were estimated by length of follow-up from pooled longitudinal data.

Results

School-level ICCs for weekday MVPA were higher in primary schools (from 0.07 (95% CI: 0.05, 0.10) to 0.08 (95% CI: 0.06, 0.11)) compared to secondary (from 0.04 (95% CI: 0.03, 0.07) to (95% CI: 0.04, 0.10)). Girls’ ICCs were similar for primary and secondary schools, but boys’ were lower in secondary. For all ages, combined the CAC was 0.60 (95% CI: 0.44–0.72), and the IAC was 0.46 (95% CI: 0.42–0.49), irrespective of follow-up time. Estimates were higher for MVPA vs sedentary time, and for weekdays vs the whole week.

Conclusions

Adequately powered studies are important to evidence effective physical activity strategies. Our estimates of the ICC, CAC and IAC may be used to plan future school-based physical activity evaluations and were fairly consistent across a range of ages and settings, suggesting that results may be applied to other high income countries with similar school physical activity provision. It is important to use estimates appropriate to the study design, and that match the intended study population as closely as possible.
Prevalence of dermatoses in geriatric singaporeans in the community - a cross-sectional study
Authors: Juay Lester , Bhupendrabhai Monil Nagad , Ahmad Siti Hafizah Binte , Wong Hung Chew , Chong Justin Wee-Min , Tan Wee Hian , Chandran Nisha Suyien
Published: August 2024

Background

Little is known about the prevalence of dermatoses in “skin-well” geriatric Singaporeans. We aim to identify the prevalence of dermatoses and their associations within the geriatric population in Singapore, and to understand the distribution of dermatological encounters presenting to primary care physicians, and the resultant referral behaviour.

Methods

A joint quantitative-qualitative study was performed across 8 months. Patients aged 65 years and above who visited a local polyclinic for management of non-dermatological chronic diseases were recruited. They were administered questionnaires, and underwent full skin examinations. Online surveys were disseminated to polyclinic physicians under the same healthcare cluster.

Results

201 patients and 53 physicians were recruited. The most common dermatoses identified in patients were benign tumours and cysts (97.5%), and asteatosis (81.6%). For every 1-year increase in age, the odds of having asteatosis increased by 13.5% (95% CI 3.4–24.7%, p = 0.008), and urticarial disorders by 14.6% (95% CI 0.3–30.9%, p = 0.045). Patients who used any form of topical preparations on a daily basis had higher odds of having eczema and inflammatory dermatoses (OR 2.51, 95% CI 1.38 to 4.56, p = 0.003). Physicians reported dermatological conditions involving 20% of all clinical encounters. Eczema represented the most commonly reported dermatosis within the first visit. 50% of dermatology referrals were done solely at the patient’s own request.

Conclusion

The prevalence of dermatoses in the elderly in Singapore is high, especially asteatosis. Prompt recognition by the primary healthcare provider potentially prevents future morbidity. Outreach education for both primary care physicians and the general public will be key.

Ethics approval

National Healthcare group (NHG) Domain Specific Review Board (DSRB), Singapore, under Trial Registration Number 2020/00239, dated 11 August 2020.
Biomarkers of Airway Disease, Barrett’s and Underdiagnosed Reflux Noninvasively (BAD-BURN) in World Trade Center exposed firefighters: a case–control observational study protocol
Authors: Javed Urooj , Podury Sanjiti , Kwon Sophia , Liu Mengling , Kim Daniel H. , Fallahzadeh Aida , Li Yiwei , Khan Abraham R. , Francois Fritz , Schwartz Theresa , Zeig-Owens Rachel , Grunig Gabriele , Veerappan Arul , Zhou Joanna , Crowley George , Prezant David J. , Nolan Anna
Published: August 2024

Background

Particulate matter exposure (PM) is a cause of aerodigestive disease globally. The destruction of the World Trade Center (WTC) exposed first responders and inhabitants of New York City to WTC-PM and caused obstructive airways disease (OAD), gastroesophageal reflux disease (GERD) and Barrett’s Esophagus (BE). GERD not only diminishes health-related quality of life but also gives rise to complications that extend beyond the scope of BE. GERD can incite or exacerbate allergies, sinusitis, bronchitis, and asthma. Disease features of the aerodigestive axis can overlap, often necessitating more invasive diagnostic testing and treatment modalities. This presents a need to develop novel non-invasive biomarkers of GERD, BE, airway hyperreactivity (AHR), treatment efficacy, and severity of symptoms.

Methods

Our observational case-cohort study will leverage the longitudinally phenotyped Fire Department of New York (FDNY)-WTC exposed cohort to identify Biomarkers of Airway Disease, Barrett’s and Underdiagnosed Reflux Noninvasively (BAD-BURN). Our study population consists of n = 4,192 individuals from which we have randomly selected a sub-cohort control group (n = 837). We will then recruit subgroups of i. AHR only ii. GERD only iii. BE iv. GERD/BE and AHR overlap or v. No GERD or AHR, from the sub-cohort control group. We will then phenotype and examine non-invasive biomarkers of these subgroups to identify under-diagnosis and/or treatment efficacy. The findings may further contribute to the development of future biologically plausible therapies, ultimately enhance patient care and quality of life.

Discussion

Although many studies have suggested interdependence between airway and digestive diseases, the causative factors and specific mechanisms remain unclear. The detection of the disease is further complicated by the invasiveness of conventional GERD diagnosis procedures and the limited availability of disease-specific biomarkers. The management of reflux is important, as it directly increases risk of cancer and negatively impacts quality of life. Therefore, it is vital to develop novel noninvasive disease markers that can effectively phenotype, facilitate early diagnosis of premalignant disease and identify potential therapeutic targets to improve patient care.

Trial registration

Name of Primary Registry: “Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BADBURN)”. Trial Identifying Number: NCT05216133. Date of Registration: January 31, 2022.
Field-applicable simultaneous multiplex LAMP assay for screening HBV and HCV co-infection in a single tube
Authors: Agel Esra , Altın Kevser Hanne
Published: August 2024

Background

Globally, around 7 to 20 million people are believed to be suffering from coinfection with both hepatitis B virus (HBV) and hepatitis C virus (HCV). The loop-mediated isothermal amplification (LAMP) approach, introduced by Notomi and colleagues, has undergone substantial advancements as an effective molecular tool that enables the simultaneous analysis of multiple samples in a single tube.

Methods

The present study examined the simultaneous detection of HBV and HCV in a single tube using melt curve analysis multiplex LAMP (mLAMP), which is based on the identification of unique melting peak temperatures. Selected regions for primer design including the S gene of HBV and the UTR gene of HCV. Primer optimization is initially performed through individual HBV and HCV LAMP analysis. Following the optimization process, the mLAMP assay was evaluated by optimizing the multiplex reaction mixture, determining the reaction time, and analyzing the limit of detection (LOD). The results are also analyzed using lateral flow dipsticks (LFD), which enable the visual detection of HBV and HCV by adding 20 pmol FITC-labeled LF primers into the reaction mixture prior the mLAMP.

Results

The LOD for the mLAMP assay was determined as 10 copies/µl, and no cross-reactivity with other microorganisms was detected. The detection results obtained from patient plasma were also visually demonstrated using LFD, and displayed significant concordance with those obtained from Real-Time Polymerase Chain Assay. The mLAMP assay revealed a diagnostic sensitivity of 95% for detecting the HBV, and LOD is 90% for HCV. The overall diagnostic sensitivity of the mLAMP assay for both viruses was 85%. The assay confirmed a specificity of 100%.

Conclusion

The mLAMP assay displays significant promise for analyzing coinfected samples by simultaneously detecting the dual targets HBV and HCV within a set temperature of 62 °C, all within a time frame of 1 h. Additionally, when paired with disposable LFD, the mLAMP assay enables rapid visual detection of assay results in a matter of minutes. The result contributes to the mLAMP assay being highly suitable for coinfection screening, particularly in field conditions.
Virus and viral components transmitted through surgical smoke; a silent danger in operating room: a systematic review
Authors: Mahdood Bahareh , Merajikhah Amirmohammad , Mirzaiee Mina , Bastami Maryam , Banoueizadeh Sara
Published: August 2024

Background

During surgical procedures, heat-generating devices are widely used producing surgical smoke (SS). Since the SS can transmit infectious viruses, this systematic review was designed to investigate the potential viruses transmitted through SS.

Methods

PubMed, Scopus, Web of Science, ProQuest, and Embase databases, along with Cochran Library, and Google Scholar search engine were searched systematically (by April 21, 2024). No language, place, and time restrictions were considered. All studies evaluating the SS and virus transmission, and whole investigations regarding the viral infections transmitted through SS were totally considered inclusion criteria. Besides, non-original, qualitative, case reports, case series, letters to the editor, editorial, and review studies were excluded from the analysis. This study was conducted in accordance with the PRISMA 2020 statement.

Results

Twenty-six eligible studies were selected and reviewed for data extraction. The results showed that the SS contains virus and associated components. Six types of viruses or viral components were identified in SS including papillomavirus (HPV, BPV), Human Immunodeficiency Virus (HIV), varicella zoster, Hepatitis B (HBV), SARS-CoV-2, and Oral poliovirus (OPV), which are spread to surgical team through smoke-producing devices.

Conclusions

Since the studies confirm the presence of viruses, and viral components in SS, the potential risk to the healthcare workers, especially in operating room (OR), seems possible. Thus, the adoption of protective strategies against SS is critical. Despite the use of personal protective equipment (PPE), these viruses could affect OR personnel in surgical procedures.
Association between COVID-19 and the incidence of type 1 diabetes in Portugal – a registry study
Authors: Bjerregaard-Andersen Morten , Da Silva Jessica , Diogo Rui , Claro Ana Raquel , Ferro Inês , Romana Andreia , Rocha Patrícia , Sá Beatriz , Lobarinhas Goreti , Rolim Sara , Juhl Claus Bogh , Højlund Kurt , Fernandes Isabel , Antunes Sónia , Félix Calha Maria Manuela , Gama Guida , Amálio Sofia , Figueiras Mariana , Silva Teresa , Rosado Margarida , Ferrão Estela , Arez Luísa , Baptista Ana , Martins Ferreira Adriana , Alba Diana , Godinho Carlos , Leite Ana Luísa , Afonso Lopes Maria de Lurdes , Sampaio Maria Lurdes , Serra-Caetano Joana , Carvalho Eugenia
Published: August 2024

Background

Viral respiratory infections may precipitate type 1 diabetes (T1D). A possible association between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, and the incidence of T1D is being determined. This study was carried out using Portuguese registries, aiming at examining temporal trends between COVID-19 and T1D.

Methods

Hospital data, comparing the incidence before and during the COVID-19 pandemic, from children and young adults diagnosed with new-onset T1D, was acquired beginning in 2017 and until the end of 2022. Data was obtained from nine different Portuguese hospital units. The impact of the COVID-19 pandemic, beginning in March 2020, was assessed comparing the annual numbers of new-onset T1D cases. The annual median levels of glucose, glycated hemoglobin (HbA1c) and fasting C-peptide at T1D diagnosis were compared. The annual number of diabetic ketoacidosis (DKA) episodes among new T1D cases was also assessed at two centers.

Results

In total, data from 574 newly diagnosed T1D patients was analyzed, including 530 (92.3%) children. The mean ages for child and adult patients were 9.1 (SD 4.4) and 32.8 (SD 13.6) years, respectively. 57.8% (331/573) were male, one patient had unknown sex. The overall median (25–75 percentiles) levels of glucose, HbA1c and fasting C-peptide at diagnosis were 454 mg/dL (356–568), 11.8% (10.1–13.4) and 0.50 µg/L (0.30–0.79), respectively. DKA at T1D diagnosis was present in 48.4% (76/157). For eight centers with complete 2018 to 2021 data (all calendar months), no overall significant increase in T1D cases was observed during the COVID-19 pandemic, i.e. 90 cases in 2018, 90 cases in 2019, 112 in 2020 and 100 in 2021 (P for trend = 0.36). Two of the centers, Faro (CHUA) and Dona Estefânia (CHULC) hospitals, did however see an increase in T1D from 2019 to 2020. No significant changes in glucose (P = 0.32), HbA1c (P = 0.68), fasting C-peptide (P = 0.20) or DKA frequency (P = 0.68) at the time of T1D diagnosis were observed over the entire study period.

Conclusion

The T1D incidence did not increase significantly, when comparing the years before and during the COVID-19 pandemic, nor did key metabolic parameters or number of DKA episodes change.
Modelling timelines to elimination of sleeping sickness in the Democratic Republic of Congo, accounting for possible cryptic human and animal transmission
Authors: Crump Ronald E. , Aliee Maryam , Sutherland Samuel A. , Huang Ching-I , Crowley Emily H. , Spencer Simon E. F. , Keeling Matt J. , Shampa Chansy , Mwamba Miaka Erick , Rock Kat S.
Published: August 2024

Background

Sleeping sickness (gambiense human African trypanosomiasis, gHAT) is a vector-borne disease targeted for global elimination of transmission (EoT) by 2030. There are, however, unknowns that have the potential to hinder the achievement and measurement of this goal. These include asymptomatic gHAT infections (inclusive of the potential to self-cure or harbour skin-only infections) and whether gHAT infection in animals can contribute to the transmission cycle in humans.

Methods

Using modelling, we explore how cryptic (undetected) transmission impacts the monitoring of progress towards and the achievement of the EoT goal. We have developed gHAT models that include either asymptomatic or animal transmission, and compare these to a baseline gHAT model without either of these transmission routes, to explore the potential role of cryptic infections on the EoT goal. Each model was independently calibrated to five different health zones in the Democratic Republic of the Congo (DRC) using available historical human case data for 2000–2020 (obtained from the World Health Organization’s HAT Atlas). We applied a novel Bayesian sequential updating approach for the asymptomatic model to enable us to combine statistical information about this type of transmission from each health zone.

Results

Our results suggest that, when matched to past case data, we estimated similar numbers of new human infections between model variants, although human infections were slightly higher in the models with cryptic infections. We simulated the continuation of screen-confirm-and-treat interventions, and found that forward projections from the animal and asymptomatic transmission models produced lower probabilities of EoT than the baseline model; however, cryptic infections did not prevent EoT from being achieved eventually under this approach.

Conclusions

This study is the first to simulate an (as-yet-to-be available) screen-and-treat strategy and found that removing a parasitological confirmation step was predicted to have a more noticeable benefit to transmission reduction under the asymptomatic model compared with the others. Our simulations suggest vector control could greatly impact all transmission routes in all models, although this resource-intensive intervention should be carefully prioritised.

Graphical Abstract
Knockdown resistance mutations in Phlebotomus argentipes sand flies in Bihar, India
Authors: Kristan Mojca , Hazelgrove Carlamarita , Kumar Kundan , Kumar Ashish , Kumar Vijay , Das Pradeep , Collins Emma , Mark-Carew Miguella , Campino Susana , Cameron Mary
Published: August 2024

Background

Vector control based on indoor residual spraying (IRS) is one of the main components of the visceral leishmaniasis (VL) elimination programme in India. Dichlorodiphenyltrichloroethane (DDT) was used for IRS until 2015 and was later replaced by the synthetic pyrethroid alpha-cypermethrin. Both classes of insecticides share the same target site, the voltage-gated sodium channel (Vgsc). As high levels of resistance to DDT have been documented in the local sand fly vector, Phlebotomus argentipes, it is possible that mutations in the Vgsc gene could provide resistance to alpha-cypermethrin, affecting current IRS pyrethroid-based vector control.

Methods

This study aimed to compare frequencies of knockdown resistance (kdr) mutations in Vgsc between two sprayed and two unsprayed villages in Bihar state, India, which had the highest VL burden of the four endemic states. Across four villages, 350 female P. argentipes were collected as part of a 2019 molecular xenomonitoring study. DNA was extracted and used for sequence analysis of the IIS6 fragment of the Vgsc gene to assess the presence of kdr mutations.

Results

Mutations were identified at various positions, most frequently at codon 1014, a common site known to be associated with insecticide resistance in mosquitoes and sand flies. Significant inter-village variation was observed, with sand flies from Dharampur, an unsprayed village, showing a significantly higher proportion of wild-type alleles (55.8%) compared with the three other villages (8.5–14.3%). The allele differences observed across the four villages may result from selection pressure caused by previous exposure to DDT.

Conclusions

While DDT resistance has been reported in Bihar, P. argentipes is still susceptible to pyrethroids. However, the presence of kdr mutations in sand flies could present a threat to IRS used for VL control in endemic villages in India. Continuous surveillance of vector bionomics and insecticide resistance, using bioassays and target genotyping, is required to inform India’s vector control strategies and to ensure the VL elimination target is reached and sustained.

Graphical Abstract
Building shape-focused pharmacophore models for effective docking screening
Authors: Moyano-Gómez Paola , Lehtonen Jukka V. , Pentikäinen Olli T. , Postila Pekka A.
Published: August 2024

The performance of molecular docking can be improved by comparing the shape similarity of the flexibly sampled poses against the target proteins’ inverted binding cavities. The effectiveness of these pseudo-ligands or negative image-based models in docking rescoring is boosted further by performing enrichment-driven optimization. Here, we introduce a novel shape-focused pharmacophore modeling algorithm O-LAP that generates a new class of cavity-filling models by clumping together overlapping atomic content via pairwise distance graph clustering. Top-ranked poses of flexibly docked active ligands were used as the modeling input and multiple alternative clustering settings were benchmark-tested thoroughly with five demanding drug targets using random training/test divisions. In docking rescoring, the O-LAP modeling typically improved massively on the default docking enrichment; furthermore, the results indicate that the clustered models work well in rigid docking. The C+ +/Qt5-based algorithm O-LAP is released under the GNU General Public License v3.0 via GitHub (https://github.com/jvlehtonen/overlap-toolkit).

Scientific contribution

This study introduces O-LAP, a C++/Qt5-based graph clustering software for generating new type of shape-focused pharmacophore models. In the O-LAP modeling, the target protein cavity is filled with flexibly docked active ligands, the overlapping ligand atoms are clustered, and the shape/electrostatic potential of the resulting model is compared against the flexibly sampled molecular docking poses. The O-LAP modeling is shown to ensure high enrichment in both docking rescoring and rigid docking based on comprehensive benchmark-testing.

Graphical Abstract
Mapping vaccine names in clinical trials to vaccine ontology using cascaded fine-tuned domain-specific language models
Authors: Li Jianfu , Li Yiming , Pan Yuanyi , Guo Jinjing , Sun Zenan , Li Fang , He Yongqun , Tao Cui
Published: August 2024

Background

Vaccines have revolutionized public health by providing protection against infectious diseases. They stimulate the immune system and generate memory cells to defend against targeted diseases. Clinical trials evaluate vaccine performance, including dosage, administration routes, and potential side effects. ClinicalTrials.gov is a valuable repository of clinical trial information, but the vaccine data in them lacks standardization, leading to challenges in automatic concept mapping, vaccine-related knowledge development, evidence-based decision-making, and vaccine surveillance.

Results

In this study, we developed a cascaded framework that capitalized on multiple domain knowledge sources, including clinical trials, the Unified Medical Language System (UMLS), and the Vaccine Ontology (VO), to enhance the performance of domain-specific language models for automated mapping of VO from clinical trials. The Vaccine Ontology (VO) is a community-based ontology that was developed to promote vaccine data standardization, integration, and computer-assisted reasoning. Our methodology involved extracting and annotating data from various sources. We then performed pre-training on the PubMedBERT model, leading to the development of CTPubMedBERT. Subsequently, we enhanced CTPubMedBERT by incorporating SAPBERT, which was pretrained using the UMLS, resulting in CTPubMedBERT + SAPBERT. Further refinement was accomplished through fine-tuning using the Vaccine Ontology corpus and vaccine data from clinical trials, yielding the CTPubMedBERT + SAPBERT + VO model. Finally, we utilized a collection of pre-trained models, along with the weighted rule-based ensemble approach, to normalize the vaccine corpus and improve the accuracy of the process. The ranking process in concept normalization involves prioritizing and ordering potential concepts to identify the most suitable match for a given context. We conducted a ranking of the Top 10 concepts, and our experimental results demonstrate that our proposed cascaded framework consistently outperformed existing effective baselines on vaccine mapping, achieving 71.8% on top 1 candidate’s accuracy and 90.0% on top 10 candidate’s accuracy.

Conclusion

This study provides a detailed insight into a cascaded framework of fine-tuned domain-specific language models improving mapping of VO from clinical trials. By effectively leveraging domain-specific information and applying weighted rule-based ensembles of different pre-trained BERT models, our framework can significantly enhance the mapping of VO from clinical trials.
Epigallocatechin-3-gallate protects bovine ruminal epithelial cells against lipopolysaccharide-induced inflammatory damage by activating autophagy
Authors: Zhao Wanli , Shen Taiyu , Zhao Bichen , Li Moli , Deng Zhaoju , Huo Yihui , Aernouts Ben , Loor Juan J. , Psifidi Androniki , Xu Chuang
Published: August 2024

Background

Subacute ruminal acidosis (SARA) causes an increase in endotoxin, which can induce immune and inflammatory responses in the ruminal epithelium of dairy cows. In non-ruminants, epigallocatechin-3-gallate (EGCG), a major bioactive ingredient of green tea, is well-known to alleviate inflammation. Whether EGCG confers protection against SARA-induced inflammation and the underlying mechanisms are unknown.

Results

In vivo, eight ruminally cannulated Holstein cows in mid-lactation were randomly assigned to either a low-concentrate (40%) diet (CON) or a high-concentrate (60%) diet (HC) for 3 weeks to induce SARA (n = 4). Cows with SARA had greater serum concentrations of tumor necrosis factor (TNF)-α and interleukin-6, and epithelium had histological signs of damage. In vitro, immortalized bovine ruminal epithelial cells (BREC) were treated with lipopolysaccharide (LPS) to imitate the inflammatory damage caused by SARA. Our data revealed that BREC treated with 10 µg/mL LPS for 6 h successfully induce a robust inflammatory response as indicated by increased phosphorylation of IκBα and nuclear factor kappa-B (NF-κB) p65. Pre-treatment of BREC with 50 µmol/L EGCG for 6 h before LPS challenge promoted the degradation of NLR family pyrin domain containing 3 (NLRP3) inflammasome through activation of autophagy, which further repressed activation of NF-κB pathway targeting Toll-like receptor 4 (TLR4). Analyses also revealed that the ECGG upregulated tight junction (TJ) protein expression upon incubation with LPS.

Conclusions

Subacute ruminal acidosis causes ruminal epithelium injury and systemic inflammation in dairy cows. However, the anti-inflammatory effects of EGCG help preserve the integrity of the epithelial barrier through activating autophagy when BREC are exposed to LPS. Thus, EGCG could potentially serve as an effective therapeutic agent for SARA-associated inflammation.

Graphical Abstract
Clinical trauma severity of indoor and outdoor injurious falls requiring emergency medical service response
Authors: Burford Kathryn G. , Itzkowitz Nicole G. , Crowe Remle P. , Wang Henry E. , Lo Alexander X. , Rundle Andrew G.
Published: August 2024

Background

Injurious falls represent a significant public health burden. Research and policies have primarily focused on falls occurring indoors despite evidence that outdoor falls account for 47–58% of all falls requiring some medical attention. This study described the clinical trauma severity of indoor versus outdoor injurious falls requiring Emergency Medical Services (EMS) response.

Methods

Using the 2019 National Emergency Medical Services Information System (NEMSIS) dataset, we identified the location of patients injured from falls that required EMS response. We classified injury severity using (1) the Revised Trauma Score for Triage (T-RTS): ≤ 11 indicated the need for transport to a Trauma Center; (2) Glasgow Coma Scale (GCS): ≤ 8 and 9–12 indicated severe and moderate neurologic injury; and (3) patient clinical acuity by EMS: Dead, Critical, Emergent, Low.

Results

Of 1,854,909 encounters for patients with injurious falls, the vast majority occurred indoors (n = 1,596,860) compared to outdoors (n = 152,994). For patients who fell indoors vs outdoors on streets or sidewalks, the proportions were comparable for moderate or severe GCS scores (3.0% vs 3.9%), T-RTS scores indicating need for transport to a Trauma Center (5.2% vs 5.9%) and EMS acuity rated as Emergent or Critical (27.7% vs 27.1%). Injurious falls were more severe among male patients compared to females and males injured by falling on streets or sidewalks had higher percentages for moderate or severe GCS scores (5.2% vs 1.9%) and T-RTS scores indicating the need for transport to a Trauma Center (7.3% vs 3.9%) compared to falling indoors. Young and middle-aged patients who fell on streets or sidewalks had higher proportions for a T-RTS score indicating the need for Trauma Center care compared to those in this subgroup who fell indoors. Yet older patients injured by falling indoors were more likely to have a T-RTS score indicating the need for transport to a Trauma Center than older patients who fell on streets or sidewalks.

Conclusions

There was a similar proportion of patients with severe injurious falls that occurred indoors and outdoors on streets or sidewalks. These findings suggest the need to determine outdoor environmental risks for outdoor falls to support location-specific interventions.
The symbiotic alga Trebouxia fuels a coherent soil ecosystem on the landscape scale in the Atacama Desert
Authors: Jung Patrick , Brand Rebekah , Briegel-Williams Laura , Werner Lina , Jost Emily , Lentendu Guillaume , Singer David , Athavale Rujuta , Nürnberg Dennis J. , Alfaro Fernando D. , Büdel Burkhard , Lakatos Michael
Published: August 2024

Biocrusts represent associations of lichens, green algae, cyanobacteria, fungi and other microorganisms, colonizing soils in varying proportions of principally arid biomes. The so-called grit crust represents a recently discovered type of biocrust situated in the Coastal Range of the Atacama Desert (Chile) made of microorganisms growing on and in granitoid pebbles, resulting in a checkerboard pattern visible to the naked eye on the landscape scale. This specific microbiome fulfills a broad range of ecosystem services, all probably driven by fog and dew-induced photosynthetic activity of mainly micro-lichens. To understand its biodiversity and impact, we applied a polyphasic approach on the phototrophic microbiome of this biocrust, combining isolation and characterization of the lichen photobionts, multi-gene phylogeny of the photobionts and mycobionts based on a direct sequencing and microphotography approach, metabarcoding and determination of chlorophylla+b contents. Metabarcoding showed that yet undescribed lichens within the Caliciaceae dominated the biocrust together with Trebouxia as the most abundant eukaryote in all plots. Together with high mean chlorophylla+b contents exceeding 410 mg m−2, this distinguished the symbiotic algae Trebouxia as the main driver of the grit crust ecosystem. The trebouxioid photobionts could be assigned to the I (T. impressa/gelatinosa) and A (T. arboricola) clades and represented several lineages containing five potential species candidates, which were identified based on the unique phylogenetic position, morphological features, and developmental cycles of the corresponding isolates. These results designate the grit crust as the only known coherent soil layer with significant landscape covering impact of at least 440 km2, predominantly ruled by a single symbiotic algal genus.
Agreement between child self-report and parent-proxy report for functioning in pediatric chronic pain
Authors: Hanania Joan W. , George Jessica Edwards , Rizzo Christie , Manjourides Justin , Goldstein Laura
Published: August 2024

Purpose

Accurate assessment of chronic pain and functional disability in children and adolescents is imperative for guiding pain management interventions. Parents have multifaceted roles in their child’s pain experience and frequently provide parent-proxy reports of pain-related functioning. However, cross-informant variance is often observed with limited understanding of contributing factors. This study aims to examine the degree of alignment between child and parent-proxy reports for Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference domain among children with chronic pain and to identify factors associated with improved child-parent agreement.

Methods

This study includes a sample of 127 youth (66.1% female) with mixed etiology chronic pain, ranging in age from 8 to 17 (M = 12.24; SD = 1.598), and their parent. Data was collected at an interdisciplinary pediatric pain clinic and online peer support groups. Measures of demographic, pain intensity, and functioning were collected.

Results

Means of parent-proxy reports were significantly lower than child self-reports on the PROMIS (p < 0.05). A statistically significant association between child’s pain intensity (β = 0.953, P < 0.05) and the difference between child self-reported and parent-proxy reported PROMIS functional interference scores was found.

Conclusion

Parents underestimated pain-related functional disability relative to children’s self-reports. The difference between the paired child self-report and parent-proxy report of functional disability was significantly associated with greater child self-reported pain intensity. Although parent-proxy reports in pediatric chronic pain is often used in research and practice, findings underscore the importance of incorporating child and adolescent self-report, when possible, to comprehensively capture the child’s pain experience and best inform clinical interventions.
Predictive ability of the REMS and HOTEL scoring systems for mortality in geriatric patients with pulmonary embolism
Authors: Özkan Abuzer , Özdemir Serdar
Published: August 2024

Background

Pulmonary embolism (PE) is an important cause of mortality and morbidity in the geriatric population. We aimed to compare the ability of the pulmonary embolism severity index (PESI), rapid emergency medicine score (REMS), and hypotension, oxygen saturation, low temperature, electrocardiogram change, and loss of independence (HOTEL) to predict prognosis and intensive care requirement in geriatric patient with PE.

Results

The median age of 132 patients was 77 (71–82) years. PESI was higher in the non-survivor group [132 (113–172)] (P =0.001). The median REMS was 8 (7–10), and it was higher in the non-survivor group [10 (7.5–12.0)] (p = 0.005). The median HOTEL score was 1 (0–2) in the whole cohort and 2 (1–3) in the non-survivor group, indicating significant difference compared to the survivor group (P = 0.001). The area under the curve (AUC) values of HOTEL, REMS, and PESI were determined as 0.72, 0.65, and 0.71, respectively. For the prediction of intensive care requirement, the AUC values of HOTEL, REMS, and PESI were 0.76, 0.75, and 0.76, respectively, with no significant difference in pairwise comparisons (PESI vs. REMS: p = 0.520, HOTEL vs. PESI: P = 0.526, REMS vs. HOTEL: P = 0.669, overall test: P = 0.96, DeLong’s test). The risk ratios of HOTEL and PESI were parallel to each other [5.31 (95% confidence interval (CI): 2.53–11.13) and 5.34 (95% CI: 2.36–12.08), respectively].

Conclusion

HOTEL and REMS were as successful as PESI in predicting short-term mortality and intensive care requirement in geriatric patients with PE. These scores are also more practical since they have fewer parameters than PESI.
Quantification of liver fat using non-invasive MRI-PDFF technique versus guided biopsy in potential liver donor
Authors: El-Assaly Hany , El-Adawy Laila Abd El-Moaty Ali , El-Latif Reda Saad Abd , Fawzi Mohamed Mohsen , Osama Ayman
Published: August 2024

Introduction

Significant hepatic steatosis affects the outcome of surgery when living donors are transplanted. The gold standard for diagnosing and evaluating hepatic steatosis is hepatic imaging-guided biopsy. Hepatic steatosis assessment using MR spectroscopy and the proton density fat fraction (MR-PDFF) method has produced positive findings.

Objectives

Is to compare the pre-operative assessment of liver fat quantification using MRI-PDFF methods, a non-invasive method, with histopathology.

Subjects and methods

A 42 potential donors were then operated surgically for liver transplantation, consequently, were available for the assessment of the efficiency and sensitivity of the radiological findings MRI-PDFF procedures and imaging-guided liver biopsy. This radiological workup of these donors was done through a period of 7 months.

Results

In many liver transplantations centers, liver imaging-guided biopsy histopathological examination is the gold standard. The study examined the MR proton density fat fraction modality, a recently developed test for hepatic steatosis measurement. The findings indicate 86.8% sensitivity, 50% specificity, 94.2% PDV, 28.5% NPV, 83.3% accuracy, and 0.684 AUC. On analyzing the fat percent, we found that the recorded fat percent using liver imaging-guided biopsy ranges between 1 and 10% with a median of 3. On the other hand, the recorded fat percent using MRI ranged between 2 and 15% with a median of 5.

Conclusion

The non-invasive magnetic resonance hepatic proton density fat fraction approach using IDEAL sequence is a reliable and accurate means of quantitatively evaluating hepatic steatosis with excellent sensitivity, specificity, and accuracy.
A local review of section 17 leave forms in conjunction with the Mental Health Act Code of Practice: recommendations for future practice
Authors: Pathmanathan Shayanthan , Edgerley Harris Georgina , Townsend Giles
Published: August 2024

Aims and method

The aim of this project was to set out recommendations for the section 17 leave form to reflect guidance provided in the Mental Health Act 1983: Code of Practice, following local Care Quality Commission feedback. We reviewed guidance in the Code and publicly available leave forms to identify items to include in the leave form. Then, we determined which publicly available leave forms included each item and reviewed whether the item should be included in the leave form and whether any reformulation was needed.

Results

Using the method described, we identified a list of items that should be included in the leave form. When comparing the leave forms of different trusts, there was considerable variation with respect to which items were included in each form.

Clinical implications

We provide some recommendations for future practice regarding section 17 leave forms to facilitate consistency with the Code and between different trusts.
A systematic review and meta-analysis of the traumatogenic phenotype hypothesis of psychosis
Authors: Onyeama Franca , Melegkovits Eirini , Yu Nicole , Parvez Ameerah , Rodrigues Artur , Billings Jo , Kelleher Ian , Cannon Mary , Bloomfield Michael A. P.
Published: August 2024

Background

Developmental trauma increases psychosis risk and is associated with poor prognosis. It has been proposed that psychosis in survivors of developmental trauma gives rise to a distinct ‘traumatogenic’ phenotype.

Aims

Given the implications for personalised treatment, we sought to explore the traumatogenic psychosis phenotype hypothesis in a systematic review and meta-analysis of studies comparing psychotic presentations between adults with and without developmental trauma histories.

Method

We registered the systematic review on PROSPERO (CRD42019131245) and systematically searched EMBASE, Medline and PsycINFO. The outcomes of interests were quantitative and qualitative comparisons in psychotic symptom expression (positive, negative, cognitive) and other domains of psychopathology, including affect regulation, sleep, depression and anxiety, between adults with and without experience of developmental trauma.

Results

Of 34 studies included (N = 13 150), 11 were meta-analysed (n = 2842). A significant relationship was found between developmental trauma and increased symptom severity for positive (Hedge's g = 0.27; 95% CI 0.10–0.44; P = 0.002), but not negative symptoms (Hedge's g = 0.13; 95% CI −0.04 to 0.30; P = 0.14). Developmental trauma was associated with greater neurocognitive, specifically executive, deficits, as well as poorer affect, dissociation and social cognition. Furthermore, psychotic symptom content thematically related to traumatic memories in survivors of developmental trauma.

Conclusions

Our findings that developmental trauma is associated with more severe positive and affective symptoms, and qualitative differences in symptom expression, support the notion that there may be a traumatogenic psychosis phenotype. However, underdiagnosis of post-traumatic stress disorder may also explain some of these findings. More research is needed to explore this further.
TSH Receptor Oligomers Associated With the TSH Receptor Antibody Reactome
Authors: Mezei Mihaly , Latif Rauf , Davies Terry F
Published: August 2024

The TSH receptor (TSHR) and its many forms are the primary antigens of Graves' disease as evidenced by the presence of TSHR antibodies of differing biological activity. The TSH holoreceptor undergoes complex posttranslational changes including cleavage of its ectodomain and oligomer formation. We have previously shown that the TSHR exists in both monomeric and dimeric structures in the thyroid cell membrane and have demonstrated, by modeling, that the transmembrane domains (TMD) can form stable dimeric structures. Based on these earlier simulations of the TSHR-TMD structure and our most recent model of the full-length TSHR, we have now built models of full-length TSHR multimers with and without TSH ligand in addition to multimers of the extracellular leucine-rich domain, the site of TSH and autoantibody binding. Starting from these models we ran molecular dynamics simulations of the receptor oligomers solvated with water and counterions; the full-length oligomers also were embedded in a dipalmitoylphosphatidylcholine bilayer. The full-length TSHR dimer and trimer models stayed in the same relative orientation and distance during 2000 ns (or longer) molecular dynamics simulation in keeping with our earlier report of TMD dimerization. Simulations were also performed to model oligomers of the leucine-rich domain alone; we found a trimeric complex to be even more stable than the dimers. These data provide further evidence that different forms of the TSHR add to the complexity of the immune response to this antigen that, in patients with autoimmune thyroid disease, generate an autoantibody reactome with multiple types of autoantibody to the TSHR.
Structure and Function of Somatostatin and Its Receptors in Endocrinology
Authors: Zhang Bo , Xue Li , Wu Zhe Bao
Published: August 2024

Somatostatin analogs, such as octreotide, lanreotide, and pasireotide, which function as somatostatin receptor ligands (SRLs), are the main drugs used for the treatment of acromegaly. These ligands are also used as important molecules for radiation therapy and imaging of neuroendocrine tumors. Somatostatin receptors (SSTRs) are canonical G protein-coupled proteins that play a role in metabolism, growth, and pathological conditions such as hormone disorders, neurological diseases, and cancers. Cryogenic electron microscopy combined with the protein structure prediction platform AlphaFold has been used to determine the 3-dimensional structures of many proteins. Recently, several groups published a series of papers illustrating the 3-dimensional structure of SSTR2, including that of the inactive/activated SSTR2-G protein complex bound to different ligands. The results revealed the residues that contribute to the ligand binding pocket and demonstrated that Trp8-Lys9 (the W-K motif) in somatostatin analogs is the key motif in stabilizing the bottom part of the binding pocket. In this review, we discuss the recent findings related to the structural analysis of SSTRs and SRLs, the relationships between the structural data and clinical findings, and the future development of novel structure-based therapies.
Metabolic states influence chicken retinal pigment epithelium cell fate decisions
Authors: Perez-Estrada J. Raúl , Tangeman Jared A. , Proto-Newton Maeve , Sanaka Harshavardhan , Smucker Byran , Del Rio-Tsonis Katia
Published: August 2024

During tissue regeneration, proliferation, dedifferentiation and reprogramming are necessary to restore lost structures. However, it is not fully understood how metabolism intersects with these processes. Chicken embryos can regenerate their retina through retinal pigment epithelium (RPE) reprogramming when treated with fibroblast factor 2 (FGF2). Using transcriptome profiling, we uncovered extensive regulation of gene sets pertaining to proliferation, neurogenesis and glycolysis throughout RPE-to-neural retina reprogramming. By manipulating cell media composition, we determined that glucose, glutamine or pyruvate are individually sufficient to support RPE reprogramming, identifying glycolysis as a requisite. Conversely, the activation of pyruvate dehydrogenase by inhibition of pyruvate dehydrogenase kinases, induces epithelial-to-mesenchymal transition, while simultaneously blocking the activation of neural retina fate. We also identified that epithelial-to-mesenchymal transition fate is partially driven by an oxidative environment. Our findings provide evidence that metabolism controls RPE cell fate decisions and provide insights into the metabolic state of RPE cells, which are prone to fate changes in regeneration and pathologies, such as proliferative vitreoretinopathy.
A meta-analysis of whole-body and heart mass effect sizes from a long-term artificial selection experiment for high voluntary exercise
Authors: Schwartz Nicole E. , Garland Theodore
Published: August 2024

Selection experiments play an increasingly important role in comparative and evolutionary physiology. However, selection experiments can be limited by relatively low statistical power, in part because replicate line is the experimental unit for analyses of direct or correlated responses (rather than number of individuals measured). One way to increase the ability to detect correlated responses is through a meta-analysis of studies for a given trait across multiple generations. To demonstrate this, we applied meta-analytic techniques to two traits (body mass and heart ventricle mass, with body mass as a covariate) from a long-term artificial selection experiment for high voluntary wheel-running behavior. In this experiment, all four replicate High Runner (HR) lines reached apparent selection limits around generations 17–27, running approximately 2.5- to 3-fold more revolutions per day than the four non-selected Control (C) lines. Although both traits would also be expected to change in HR lines (relative heart size expected to increase, expected direction for body mass is less clear), their statistical significance has varied, despite repeated measurements. We compiled information from 33 unique studies and calculated a measure of effect size (Pearson's R). Our results indicate that, despite a lack of statistical significance in most generations, HR mice have evolved larger hearts and smaller bodies relative to controls. Moreover, plateaus in effect sizes for both traits coincide with the generational range during which the selection limit for wheel-running behavior was reached. Finally, since reaching the selection limit, absolute effect sizes for body mass and heart ventricle mass have become smaller (i.e. closer to 0).