bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cosmological constant and scale hierarchies with emergent gauge symmetries
Authors: Bass Steven D. 
Published: December 2023

Motivated by the stability of the electroweak Higgs vacuum we consider the possibility that the Standard Model might work up to large scales between about

10

10

GeV and close to the Planck scale. A plausible scenario is an emergent Standard Model with gauge symmetries originating in some topological-like phase transition deep in the ultraviolet. In this case, the cosmological constant scale and neutrino masses should be of similar size, suppressed by factor of the large scale of emergence. The key physics involves a subtle interplay of Poincaré invariance, mass generation and renormalization group invariance. The Higgs mass would be environmentally selected in connection with vacuum stability. Consequences for dark matter scenarios are discussed.

This article is part of the theme issue ‘The particle-gravity frontier’.
Plasma neurofilament light chain is elevated in Niemann-Pick Type C but glial fibrillary acidic protein is not
Authors: Eratne Dhamidhu , Lewis Courtney , Kelso Wendy , Loi Samantha , Chiu Wei-Hsuan Michelle , Blennow Kaj , Zetterberg Henrik , Santillo Alexander F , Velakoulis Dennis , Walterfang Mark ,   And The MiND Study Group
Published: December 2023

ABSTRACTOBJECTIVENiemann-Pick Type C (NPC) is a genetic neurodegenerative lysosomal storage disorder commonly associated with psychiatric symptoms and delays to accurate diagnosis and treatment. This study investigated biomarker levels and diagnostic utility of plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in NPC compared to healthy controls.METHODSPatients with NPC were recruited from a specialist assessment and management service. Data was available from an age and sex-matched healthy control group. NfL and GFAP were measured on Quanterix Simoa HD-X analysers and groups compared using genralised linear models. NfL levels were compared to, and percentiles derived from, recently developed NfL reference ranges.RESULTSPlasma NfL was significantly elevated in 11 patients with NPC compared to 25 controls (mean 17.1pg/mL vs 7.4pg/mL, p<0.001), and reference ranges (all >98thpercentile). NfL distinguished NPC from controls with high accuracy. GFAP levels were not elevated in NPC (66.6pg/mL vs 75.1pg/mL).DISCUSSIONThe study adds important evidence on the potential diagnostic utility of plasma NfL in NPC, extends the literature of NfL as a diagnostic tool to differentiate neurodegenerative from primary psychiatric disorders, and adds support to the pathology in NPC primarily involving neuronal, particularly axonal, degeneration.
Capture of Group A Streptococcus by Open-Microfluidic CandyCollect Device in Pediatric Patients
Authors: Tu Wan-chen , Robertson Ingrid H. , Blom Andrea , Alfaro Elena , Shinkawa Victoria A. M. , Hatchett Daniel B. , Sanchez Juan C. , McManamen Anika M. , Su Xiaojing , Berthier Erwin , Thongpang Sanitta , Wald Ellen R. , DeMuri Gregory P. , Theberge Ashleigh B. 
Published: December 2023

AbstractState the purposeObtaining high-quality samples to diagnose streptococcal pharyngitis in pediatric patients is challenging due to discomfort associated with traditional pharyngeal swabs. This may cause reluctance to go to the clinic, inaccurate diagnosis, or inappropriate treatment for children with sore throat. Here, we determined the efficacy of CandyCollect, a lollipop-inspired open-microfluidic pathogen collection device, to capture Group A Streptococcus (GAS) and compare user preference for CandyCollect, conventional pharyngeal swabs, or mouth swabs in children with pharyngitis and their caregivers.ResultsAll child participants (30/30) were positive for GAS by qPCR on both the mouth swab and CandyCollect. Caregivers ranked CandyCollect as a good sampling method overall (27/30), and all caregivers (30/30) would recommend CandyCollect for children 5 years and older. Twenty-three of 30 children “really like” the taste and 24/30 would prefer to use CandyCollect if a future test were needed. All caregivers (30/30) and most children (28/30) would be willing to use CandyCollect at home.ConclusionAll participants tested positive for GAS on all three collection methods (pharyngeal swab, mouth swab, and CandyCollect). While both caregivers and children like CandyCollect, some caregivers would prefer a shorter collection time. Future work includes additional studies with larger cohorts presenting with pharyngitis of unknown etiology and shortening collection time while maintaining the attractive form of the device.Translational Impact StatementObtaining oral samples for the diagnosis of streptococcal pharyngitis is of great importance for children. To address the challenges associated with traditional pharyngeal swab sampling, we developed the CandyCollect device, a lollipop-inspired open mesofluidic saliva sampling system. In this study, saliva samples were collected from children, aged 5-14 years, with CandyCollect and mouth swabs and analyzed via qPCR. The results show CandyCollect is the child preferred collection tool and had 100% concordance with the results from traditional diagnosis methods as part of their clinical care.
Integration of pharmacists’ knowledge into a predictive model for teicoplanin dose planning
Authors: Matsuzaki Tetsuo , Nakai Tsuyoshi , Kato Yoshiaki , Yamada Kiyofumi , Yagi Tetsuya 
Published: December 2023

AbstractTeicoplanin is an important antimicrobial agent for methicillin-resistantStaphylococcus aureusinfections. To enhance its clinical effectiveness while preventing adverse effects, therapeutic drug monitoring (TDM) of teicoplanin trough concentration is recommended. Given the importance of the early achievement of therapeutic concentrations for treatment success, initial dosing regimens are deliberately designed based on patient information.Considerable effort has been dedicated to developing an optimal initial dose plan for specific populations; however, comprehensive strategies for tailoring teicoplanin dosing have not been successfully implemented. The initial dose planning of teicoplanin is conducted at the clinician’s discretion and is thus strongly dependent on the clinician’s experience and expertise.The present study aimed to use a machine learning (ML) approach to integrate clinicians’ knowledge into a predictive model for initial teicoplanin dose planning. We first confirmed that dose planning by pharmacists dedicated to TDM (hereafter TDM pharmacists) significantly improved early therapeutic target attainment for patients without an intensive care unit or high care unit stay, providing the first evidence that dose planning of teicoplanin by experienced clinicians enhances early teicoplanin therapeutic exposure. Next, we used a dataset of teicoplanin initial dose planning by TDM pharmacists to train and implement the model, yielding a model that emulated TDM pharmacists’ decision-making for dosing. We further applied ML to cases without TDM pharmacist dose planning and found that the target attainment rate of the initial teicoplanin concentration markedly increased. Our study opens a new avenue for tailoring the initial dosing regimens of teicoplanin using a TDM pharmacist-trained ML system.ImportanceTeicoplanin is used for treating methicillin-resistantStaphylococcus aureusinfections. Given the importance of early adequate teicoplanin exposure, initial dosing regimens are adjusted for patient characteristics. However, tailoring teicoplanin dosing is challenging for most clinicians. In this study, we first showed that initial dosing regimens by pharmacists dedicated to therapeutic drug monitoring significantly improved early achievement of targeted concentration. In addition, we leveraged machine learning approach to develop the predictive model that tailors initial dosing regimens at the levels of experienced pharmacists. The target attainment rate of patients without experienced pharmacists’ dose planning was significantly increased by applying the model. Therefore, machine learning approach may provide new avenues for tailoring initial teicoplanin dosing.
Impact of a multi-pronged cholera intervention in an endemic setting
Authors: Blake Alexandre , Walder Adam , Hanks Ephraim , Welo Placide Okitayembo , Luquero Francisco , Bompangue Didier , Bharti Nita 
Published: December 2023

AbstractCholera is a bacterial water-borne diarrheal disease transmitted via the fecal-oral route that causes high morbidity in sub-Saharan Africa and Asia. It is preventable with vaccination, and Water, Sanitation, and Hygiene (WASH) improvements. However, the impact of vaccination in endemic settings remains unclear. Cholera is endemic in the city of Kalemie, on the shore of Lake Tanganyika, in the Democratic Republic of Congo, where both seasonal mobility and the lake, a potential environmental reservoir, may promote transmission. Kalemie received a vaccination campaign and WASH improvements in 2013-2016. We assessed the impact of this intervention to inform future control strategies in endemic settings.We fit compartmental models considering seasonal mobility and environmentally-based transmission. We estimated the number of cases the intervention avoided, and the relative contributions of the elements promoting local cholera transmission.We estimated the intervention avoided 5,259 cases (95% credible interval: 1,576.6-11,337.8) over 118 weeks. Transmission did not rely on seasonal mobility and was primarily environmentally-driven. Removing environmental exposure or contamination could control local transmission.Repeated environmental exposure could maintain high population immunity and decrease the impact of vaccination in similar endemic areas. Addressing environmental exposure and contamination should be the primary target of interventions in such settings.Author summaryCholera is a major global health concern that causes high morbidity. It is a bacterial water-borne disease that can be transmitted via the fecal-oral route or the ingestion of contaminated water. Hence, both population mobility and environmental exposure can promote cholera persistence. The primary tools to prevent cholera include vaccination and Water, Sanitation, and Hygiene (WASH) improvements. The effectiveness of these interventions is well understood in epidemic settings, but their impact in endemic settings is unclear. Achieving cholera elimination requires disentangling the contributors to transmission, specifically population mobility and aquatic reservoirs, and assessing the impact of interventions performed in endemic settings.This study focuses on Kalemie, a cholera endemic city in the Democratic Republic of Congo, on shore of a lake that serves as a potential environmental reservoir. It quantifies the short-term impact of an intervention that used targeted vaccination and WASH. The study shows that the impact of vaccination was dampened by very high background immunity due to constant environmental exposure. This suggests that WASH improvements should be the primary intervention in such settings despite the time- and resource-intensive nature of implementation.
Evaluation of gastric electrophysiology, symptoms and quality of life after pancreaticoduodenectomy
Authors: Wang Tim Hsu-Han , Varghese Chris , Calder Stefan , Gharibans Armen , Schamberg Gabriel , Bartlett Adam , Srinivasa Sanket , O’Grady Greg 
Published: December 2023

AbstractBackgroundPancreaticoduodenectomy (PD) is an operation performed for several indications, including pancreatic and biliary malignancies. Delayed gastric emptying (DGE) is a common post-operative complication and the underlying pathophysiology remains poorly understood. This study aimed to evaluate the gastric electrophysiology, symptoms and quality of life following PD, using the novel non-invasive Gastric Alimetry System.MethodsPD patients with index operations between 2017-2022 were assessed using the Gastric Alimetry System®, comprising a stretchable 8×8 electrode array, wearable Reader, and validated symptom logging app. A 30-minute pre-prandial and a 4-hour post-prandial recording was performed. Outcomes included Principal Gastric Frequency, BMI-adjusted amplitude, Gastric Alimetry Rhythm Index, meal response, symptoms, and quality of life (QOL) questionnaires (PAGI-SYM, PAGI-QOL). Data was compared to a validated reference range and matched healthy controls.Results19 patients and 19 matched controls were recruited. There were no differences in any gastric parameters between PD patients and matched controls (allp>0.05). Gastric electrophysiology parameters lay outside normative reference intervals in 8/19 cases, generally being only minor deviations, while significant symptoms occurred in 8/19 (42%); which did not correlate (p=0.43). PD patients had worse quality of life scores than controls (p<0.01), however, no correlations were identified between electrophysiological parameters and QOL.DiscussionModerate to severe upper GI symptoms are common after PD with worse QOL compared to the controls. Gastric electrical activity generally recovers well long-term following PD, indicating that other factors contribute to symptoms. Further studies should now assess acute changes in gastric function after PD.
Variations in Risk Factors across Different Periods of Stroke Recurrence
Authors: Lee Sang-Hun , Jung Jin-Man , Ryu Jae-Chan , Park Moon-Ho 
Published: December 2023

AbstractBackground and PurposeAccurately discerning periods of heightened risk of stroke recurrence and managing modifiable risk factors are essential for minimizing overall recurrence risk. This study identified differences in the timing of stroke recurrence based on risk factors and patient characteristics to develop strategies for reducing recurrence in clinical practice.MethodsWe retrospectively selected patients with ischemic stroke or transient ischemic attack at the Korea University Ansan Hospital Stroke Center between March 2014 and December 2021 using the prospective institutional database of the Korea University Stroke Registry. We collected demographic, clinical, and stroke data and categorized participants by recurrence timing (early within 3 months or late after 3 months). Using multinomial logistic regression analysis, we examined variables associated with early and late recurrent strokes.ResultsThe analysis included 3,646 patients, of whom 255 experienced a recurrent stroke and 3,391 experienced their first stroke. Multinomial logistic regression analysis revealed significant associations between early recurrent stroke and diabetes mellitus (OR 1.98, 95% CI 1.25–3.15), other determined etiologies in TOAST classification (OR 3.00, 95% CI 1.37– 6.61), and white matter changes (OR 1.97, 95% CI 1.17–3.33). Late recurrent stroke showed a significant correlation with transient ischemic attack (TIA) (OR 2.95, 95% CI 1.52–5.71) and cerebral microbleeds (OR 2.22, 95% CI 1.32–3.75).ConclusionOur study emphasizes substantial differences in factors contributing to stroke recurrence based on timing. Managing the risk of recurrence in clinical practice necessitates accurate identification of heightened risk periods and rigorous control of modifiable risk factors.
Adiposity and Sex Influence on SARS-CoV-2 Antibody Response in University Students. An ESFUERSO cross-sectional study
Authors: Perales-Torres Adriana L. , Perez-Navaro Lucia M. , Garcia-Oropesa Esperanza M. , Diaz-Badillo Alvaro , Martinez-Lopez Yoscelina Estrella , Rosas Marisol , Castillo Octelina , Ramirez-Quintanilla Laura , Cervantes Jacquelynne , Sciutto Edda , Cisneros Claudia X. Munguia , Ramirez-Pfeifer Carlos , Vela Leonel , Tapia Beatriz , Lopez-Alvarenga Juan C. 
Published: December 2023

AbstractIntroductionPrior studies have identified various determinants of differential immune responses to COVID-19. This investigation delves into the Ig-G anti-RBD marker, scrutinizing its potential correlations with sex, vaccine type, body fat percentage, metabolic risk, perceived stress, and previous COVID-19 exposure.MethodsIn this study, data were obtained from 116 participants from the ESFUERSO cohort, who completed questionnaires detailing their COVID-19 experiences and stress levels assessed through the SISCO scale. Quantification of Ig-G anti-RBD concentrations was executed using an ELISA assay developed by UNAM. Multiple regression analysis was adeptly employed to control for covariates, including sex, age, body fat percentage, BMI, and perceived stress.ResultsThis sample comprised young individuals (average age of 21.4 years), primarily consisting of females (70%), with a substantial proportion reporting a family history of diabetes, hypertension, or obesity. Most students had received the Moderna or Pfizer vaccines, and 91% displayed a positive anti-RBD response.A noteworthy finding was the interaction between body fat percentage and sex. In males, increased adiposity was associated with a decrease in Ig-G anti-RBD concentration, while in females, the response increased. Importantly, this trend was consistent regardless of the vaccine received. No significant associations were observed for variables such as dietary habits or perceived stress.ConclusionsIn summation, this research reports the impact of both sex and body fat percentage on the immune response through Ig-G anti-RBD levels to COVID-19 vaccines. The implications of these findings offers a foundation for educational initiatives and the formulation of preventive policies aimed at mitigating health disparities.
Limitations in next-generation sequencing-based genotyping of breast cancer polygenic risk score loci
Authors: Baumann Alexandra , Ruckert Christian , Meier Christoph , Hutschenreiter Tim , Remy Robert , Schnur Benedikt , Döbel Marvin , Nkouamedjo Fankep Rudel Christian , Skowronek Dariush , Kutz Oliver , Arnold Norbert , Katzke Anna-Lena , Forster Michael , Kobiela Anna-Lena , Thiedig Katharina , Zimmer Andreas , Ritter Julia , Weber Bernhard H.F. , Honisch Ellen , Hackmann Karl ,   Bioinformatics Working Group of the German Consortium for Hereditary Breast & Ovarian Cancer, Schmidt Gunnar , Sturm Marc , Ernst Corinna 
Published: December 2023

AbstractConsidering polygenic risk scores (PRSs) in individual risk prediction is increasingly becoming the standard in genetic testing for hereditary breast cancer (BC). To calculate individual BC risks, the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) with inclusion of the BCAC 313 or the BRIDGES 306 BC PRS is commonly used. Meaningful incorporation of PRSs relies on reproducing the allele frequencies (AFs), and hence, the distribution of PRS values, expected by the algorithm. Here, the 324 loci of the BCAC 313 and the BRIDGES 306 BC PRS were examined in population-specific database gnomAD and in real-world data sets of five centers of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), to determine whether these expected AFs are achieved with next-generation sequencing-based genotyping. Four PRS loci were non-existent in gnomAD v3.1.2 non-Finnish Europeans, further 24 loci showed noticeably deviating AFs. In real-world data, between 16 and up to 22 loci were reported with noticeably deviating AFs, and were shown to have effects on final risk prediction. Deviations depended on sequencing approach, variant caller and calling mode (forced versus unforced) employed. Therefore, this study demonstrates the necessity to apply quality assurance not only in terms of sequencing coverage but also observed AFs in a sufficiently large sample, when implementing PRSs in a routine diagnostic setting. Furthermore, future PRS design should be guided by reproducibility of expected AFs in addition to the observed effect sizes.
Rapid resistance detection is reliable for prompt adaptation of isoniazid resistant tuberculosis management
Authors: Bahuaud Olivier , Genestet Charlotte , Hodille Elisabeth , Vallée Maxime , Testard Quentin , Tataï Caroline , Saison Julien , Rasigade Jean-Philippe , Lina Gérard , Ader Florence , Dumitrescu Oana 
Published: December 2023

AbstractObjectivesAppropriate tuberculosis (TB) management requires anti-TB drugs resistance detection. We assessed the performance of rapid resistance detection assays and their impact on treatment adaptation, focusing on isoniazid resistant (HR) TB.MethodsFrom 2016 to 2022, all TB cases enrolled in 3 hospitals were reviewed for phenotypic drug susceptibility testing (p-DST) and genotypic DST (g-DST) performed by rapid molecular testing, and next generation sequencing (NGS). Clinical characteristics, treatment and outcome were collected for HR-TB patients. The concordance between g-DST and p-DST results, and delay between treatment initiation and results of g-DST and p-DST were respectively recorded to assess the contribution of DST results on HR-TB management.ResultsAmong 654 TB cases enrolled, 29 were HR-TB. Concordance between g-DST by rapid molecular methods and p-DST was 76.9%, whilst concordance between NGS-based g-DST and p-DST was 98.7%. Rapid resistance detection significantly fastened HR-TB treatment adaptation (median delay between g-DST results and treatment modification was 6 days). It consisted in fluoroquinolone implementation for 17/23 patients; outcome was favourable except for 2 patients who died before DST reporting.ConclusionRapid resistance detection fastened treatment adaptation. Also, NGS-based g-DST showed almost perfect concordance with p-DST, thus providing rapid and safe culture-free DST alternative.
Emergence and predominance of novel influenza A (H3N2) subclade (3C.2a1b.2a.2a.3a.1) in Kenya and globally in 2023
Authors: Morobe John Mwita , Moraa Edidah , Lambisia Arnold W. , Mutunga Martin , Kiage Brenda , Katama Esther Nyadzua , Makori Timothy , Nyiro Joyce , Ndwiga Leonard , Nyagwange James , Sande Charles , Ochola-Oyier Lynette Isabella , Holmes Edward C. , Nokes D. James , Githinji George , Agoti Charles N. 
Published: December 2023

AbstractWe report emergence and predominance of the influenza A (H3N2)subclade 3C.2a1b.2a.2a.3a.1 in Kenya similar to the global clade in 2023. The Kenyan 3C.2a1b.2a.2a.3a.1 viruses have >15 amino acid differences in the HA and NA proteins relative to 2023/24 WHO recommended Northern/Southern Hemisphere influenza vaccine strains.