bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional protection in J20/VLW mice: a model of non-demented with Alzheimer’s disease neuropathology
Authors: Dávila-Bouziguet Eva , Casòliba-Melich Arnau , Targa-Fabra Georgina , Galera-López Lorena , Ozaita Andrés , Maldonado Rafael , Ávila Jesús , Delgado-García José M , Gruart Agnès , Soriano Eduardo , Pascual Marta 
Published: August 2021

Abstract
Alzheimer’s disease comprises amyloid-β and hyperphosphorylated Tau accumulation, imbalanced neuronal activity, aberrant oscillatory rhythms and cognitive deficits. Non-demented with Alzheimer’s disease neuropathology defines a novel clinical entity with amyloid-β and Tau pathologies but preserved cognition. The mechanisms underlying such neuroprotection remain undetermined and animal models of non-demented with Alzheimer’s disease neuropathology are currently unavailable.
We demonstrate that J20/VLW mice (accumulating amyloid-β and hyperphosphorylated Tau) exhibit preserved hippocampal rhythmic activity and cognition, as opposed to J20 and VLW animals, which show significant alterations. Furthermore, we show that the overexpression of mutant human Tau in coexistence with amyloid-β accumulation renders a particular hyperphosphorylated Tau signature in hippocampal interneurons. The GABAergic septohippocampal pathway, responsible for hippocampal rhythmic activity, is preserved in J20/VLW mice, in contrast to single mutants.
Our data highlight J20/VLW mice as a suitable animal model in which to explore the mechanisms driving cognitive preservation in non-demented with Alzheimer’s disease neuropathology. Moreover, they suggest that a differential Tau phosphorylation pattern in hippocampal interneurons prevents the loss of GABAergic septohippocampal innervation and alterations in local field potentials, thereby avoiding cognitive deficits.
Pharmacokinetics of First-Line Drugs in Children With Tuberculosis, Using World Health Organization–Recommended Weight Band Doses and Formulations
Authors: Chabala Chishala , Turkova Anna , Hesseling Anneke C , Zimba Kevin M , van der Zalm Marieke , Kapasa Monica , Palmer Megan , Chirehwa Maxwell , Wiesner Lubbe , Wobudeya Eric , Kinikar Aarti , Mave Vidya , Hissar Syed , Choo Louise , LeBeau Kristen , Mulenga Veronica , Aarnoutse Robb , Gibb Diana , McIlleron Helen 
Published: August 2021

Abstract

Background
Dispersible pediatric fixed-dose combination (FDC) tablets delivering higher doses of first-line antituberculosis drugs in World Health Organization–recommended weight bands were introduced in 2015. We report the first pharmacokinetic data for these FDC tablets in Zambian and South African children in the treatment-shortening SHINE trial.

Methods
Children weighing 4.0–7.9, 8.0–11.9, 12.0–15.9, or 16.0–24.9 kg received 1, 2, 3, or 4 tablets daily, respectively (rifampicin/isoniazid/pyrazinamide [75/50/150 mg], with or without 100 mg ethambutol, or rifampicin/isoniazid [75/50 mg]). Children 25.0–36.9 kg received doses recommended for adults &lt;37 kg (300, 150, 800, and 550 mg/d, respectively, for rifampicin, isoniazid, pyrazinamide, and ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment.

Results
In the 77 children evaluated, the median age (interquartile range) was 3.7 (1.4–6.6) years; 40 (52%) were male and 20 (26%) were human immunodeficiency virus positive. The median area under the concentration-time curve from 0 to 24 hours for rifampicin, isoniazid, pyrazinamide, and ethambutol was 32.5 (interquartile range, 20.1–45.1), 16.7 (9.2–25.9), 317 (263–399), and 9.5 (7.5–11.5) mg⋅h/L, respectively, and lower in children than in adults for rifampicin in the 4.0–7.9-, 8–11.9-, and ≥25-kg weight bands, isoniazid in the 4.0–7.9-kg and ≥25-kg weight bands, and ethambutol in all 5 weight bands. Pyrazinamide exposures were similar to those in adults.

Conclusions
Recommended weight band–based FDC doses result in lower drug exposures in children in lower weight bands and in those ≥25 kg (receiving adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current World Health Organization–recommended doses requires further evaluation.
Molecular Diagnosis of Pneumonia (Including Multiplex Panels)
Authors: Buchan Blake W , Armand-Lefevre Laurence , Anderson Neil 
Published: August 2021

Abstract

Background
Pneumonia is a common illness, accounting for a staggering amount of worldwide morbidity and mortality. The diagnosis of pneumonia is challenging given the variety of responsible pathogens. Diagnostic testing for bacterial pneumonia has traditionally relied on time-consuming culture-based methods, though recently multiplexed molecular approaches have been described. Multiplexed molecular assays for pneumonia have the potential to provide broad diagnostic information in a rapid timeframe. Much has yet to be learned about these assays regarding analytical performance, potential impact, and optimal implementation strategy.

Content
Herein we provide a summary of what is known and what has yet to be learned about multiplexed molecular pneumonia assays. We provide a comparison of the different commercially available assays and summarize the most current performance data for each. We further describe outcome data and lessons learned from those who have implemented these assays worldwide. Finally, based on the current state of performance and outcome data, we provide informed strategies and considerations for laboratories contemplating implementation.

Summary
Multiplexed molecular assays for the diagnosis of pneumonia boast high accuracy though the diagnostic information gained from these assays is inherently different from culture and must be interpreted in cultural context. Despite this, these assays can be powerful and effective diagnostic tools with a potential to positively impact patient care. The extent to which this is realized varies from setting to setting, though is dependent on thoughtful implementation and a focus on delivering clear, rapid, and actionable results that can be interpreted in the appropriate context.
Low coronary flow relative to myocardial mass predicts heart failure in symptomatic hypertensive patients with no obstructive coronary artery disease
Authors: Brown Jenifer M , Zhou Wunan , Weber Brittany , Divakaran Sanjay , Barrett Leanne , Bibbo Courtney F , Hainer Jon , Taqueti Viviany R , Dorbala Sharmila , Blankstein Ron , Di Carli Marcelo F 
Published: August 2021

Abstract

Aims
The transition from hypertension to heart failure (HF) remains poorly understood. We hypothesized that insufficient perfusion to match global metabolic demand, reflected by a low ratio of myocardial blood flow to global myocardial mass, may be a HF risk marker.

Methods and results
A retrospective cohort (n = 346) of patients with hypertension who underwent clinical positron emission tomography (PET) myocardial perfusion imaging for chest pain and/or dyspnoea at Brigham and Women’s Hospital (Boston, MA, USA) were studied. Patients without obstructive coronary artery disease by history or PET perfusion (summed stress score &lt;3), HF, cardiomyopathy, or ejection fraction (EF) &lt;40% were followed for HF hospitalization (primary outcome), all-cause death, and their composite. Myocardial blood flow, left ventricular (LV) mass, volumes, and EF were obtained from PET, and a ‘flow/mass ratio’ was determined as hyperaemic myocardial blood flow over LV mass indexed to body surface area. A lower flow/mass ratio was independently associated with larger end-diastolic (β = −0.44, P &lt; 0.001) and end-systolic volume (β = −0.48, P &lt; 0.001) and lower EF (β = 0.33, P &lt; 0.001). A flow/mass ratio below the median was associated with an adjusted hazard ratio of 2.47 [95% confidence interval (CI) 1.24–4.93; P = 0.01] for HF hospitalization, 1.95 (95% CI 1.12–3.41; P = 0.02) for death, and 2.20 (95% CI 1.39–3.49; P &lt; 0.001) for the composite.

Conclusion
An integrated physiological measure of insufficient myocardial perfusion to match global metabolic demand identifies subclinical hypertensive heart disease and elevated risk of HF and death in symptomatic patients with hypertension but without flow-limiting coronary artery disease.
Treatment and survival following in-hospital cardiac arrest: does patient ethnicity matter?
Authors: Agerström Jens , Carlsson Magnus , Bremer Anders , Herlitz Johan , Rawshani Araz , Årestedt Kristofer , Israelsson Johan 
Published: August 2021

Abstract

Aims
Previous research on racial/ethnic disparities in relation to cardiac arrest has mainly focused on black vs. white disparities in the USA. The great majority of these studies concerns out-of-hospital cardiac arrest (OHCA). The current nationwide registry study aims to explore whether there are ethnic differences in treatment and survival following in-hospital cardiac arrest (IHCA), examining possible disparities towards Middle Eastern and African minorities in a European context.

Methods and results
In this retrospective registry study, 24 217 patients from the IHCA part of the Swedish Registry of Cardiopulmonary Resuscitation were included. Data on patient ethnicity were obtained from Statistics Sweden. Regression analysis was performed to assess the impact of ethnicity on cardiopulmonary resuscitation (CPR) delay, CPR duration, survival immediately after CPR, and the medical team’s reported satisfaction with the treatment. Middle Eastern and African patients were not treated significantly different compared to Nordic patients when controlling for hospital, year, age, sex, socioeconomic status, comorbidity, aetiology, and initial heart rhythm. Interestingly, we find that Middle Eastern patients were more likely to survive than Nordic patients (odds ratio = 1.52).

Conclusion
Overall, hospital staff do not appear to treat IHCA patients differently based on their ethnicity. Nevertheless, Middle Eastern patients are more likely to survive IHCA.
Development of a diagnostic model focusing on nutritional indicators for frailty classification in people with chronic heart failure
Authors: Gu Yiqin , Li Chaofeng , Yan Jing , Yin Guoping , Lu Guilan , Sha Li , Song Yan , Wang Yanyan 
Published: August 2021

AbstractAimsFrailty has a great impact on the quality of life of patients with chronic heart failure (CHF), which needs to be judged in time. To develop a diagnostic model based on nutritional indicators to judge the frailty status of patients with chronic heart failure (Frailty-CHF).Methods and resultsIn the data collection part of this study, questionnaire method and biomedical measurement method were adopted. The trace elements in serum samples were detected by high performance liquid chromatography, chemiluminescence, and inductively coupled plasma mass spectrometry. We used Excel for data consolidation, and then imported the data into R software for modelling. Lasso method was used for variable screening, and Logistics regression fitting model was used after variables were determined. The internal validation of the model was completed by Bootstrap re-sampling. A total of 123 patients were included in this study. After variables’ screening, age, nutritional status-heart failure, New York Heart Association Functional Class (NYHA), micronutrients B12, Ca, folic acid, and Se were included in the model, the c statistic and Brier score of the original model were 0.9697 and 0.0685, respectively. After Bootstrap re-sampling adjustment, the c statistic and Brier score were 0.8503 and 0.1690.ConclusionIn this study, a diagnostic model of age, nutritional status-heart failure, NYHA, the micronutrients B12, Ca, folic acid, and Se was established. It could help healthcare professionals better identify the frailty status in patients with CHF.
Exploring health coaching and mindfulness as levers for transformation in health: stakeholder perspectives
Authors: Gupta Rahul K , Mayhew Maureen , Woollard Robert , Gelb Karen 
Published: August 2021

AbstractBackgroundHealth coaching (HC) and mindfulness (MFN) are proven interventions for mobilizing patients’ inner resources and are slowly being integrated into public primary care. Since 2015 the medical community in Gibsons BC has integrated physician-led HC and MFN-based programs into team-based care. This exploratory study aimed to understand the mechanisms by which these rural programs helped both patients and clinicians, and to elicit priorities for future study in these fields.MethodsUsing a qualitative participant-engaged constructivist approach in focus groups and large-group graphic facilitation, we elicited perspectives from patients and their physicians during a 1-day event held in September 2018. Thematic analysis of transcripts using Nvivo identified emergent themes that were regularly reviewed with coresearchers, and member checked with participants via online videoconferences held at 6 weeks and 4 months postevent.ResultsWe identified six main themes relating to the successful implementation of these programs: (i) accessibility and affordability, (ii) offering a toolbox of practical skills, (iii) providing attuned and openhearted care, (iv) generating hope and self-efficacy, (v) experiencing a shared humanity and connection, and (vi) addressing the health of the whole person.ConclusionThese themes highlight critical qualities of HC and MFN programs when implemented in a Medicare system. Key features include reducing stigma around mental health through making programs physician-led and a natural part of primary care, enriching accessibility through public funding, and enhancing patient agency through cultivating embodied awareness, self-compassion, and interpersonal skills. These themes inform the next steps to support upscaling these programs to other communities.
The role of general practitioners in managing the COVID-19 pandemic in a private healthcare system
Authors: Cohidon Christine , El Hakmaoui Fatima , Senn Nicolas 
Published: August 2021

AbstractBackgroundThe canton of Vaud’s public health authorities, in Switzerland, invited general practitioners (GPs) to participate in managing suspected COVID-19 patients and continue caring for their non-COVID-19 patients. However, this course of action was not mandatory. The present study’s objective was to describe and understand how involved GPs were in dealing with the COVID-19 pandemic’s first wave.MethodsThis mixed-methods study combined a retrospective quantitative survey and a qualitative explanatory investigation. All of the canton’s GPs were invited to participate in the quantitative survey via an online questionnaire including sections on: specific organization regarding COVID-19 activities and suspected COVID-19 patients, activities relating to non-COVID-19 patients, consequences on the practice’s professional staff, and opinions about the public health authorities’ pandemic crisis management. The qualitative investigation involved interviews with 10 volunteer GPs.ResultsThe participation rate was 41%. One third of GPs chose not to reorganize their practice for the specific management of suspected COVID-19 patients. The number of weekly activities and interventions decreased by over 50% at 44% of practices, mostly due to a lack of patients. Even in an extraordinary crisis, GPs maintained their choice of whether to become involved, as their private and independent status allowed them to do. However, those who chose to be involved felt frustrated that the public health authorities did not recognize them as major health providers in the management of the pandemic.ConclusionThis study illustrated the complexity and limitations of a primary care system based completely on private healthcare providers.
The N.C.Yeastract and CommunityYeastract databases to study gene and genomic transcription regulation in non-conventional yeasts
Authors: Godinho Cláudia P , Palma Margarida , Oliveira Jorge , Mota Marta N , Antunes Miguel , Teixeira Miguel C , Monteiro Pedro T , Sá-Correia Isabel 
Published: August 2021

ABSTRACTResponding to the recent interest of the yeast research community in non-Saccharomyces cerevisiae species of biotechnological relevance, the N.C.Yeastract (http://yeastract-plus.org/ncyeastract/) was associated to YEASTRACT + (http://yeastract-plus.org/). The YEASTRACT + portal is a curated repository of known regulatory associations between transcription factors (TFs) and target genes in yeasts. N.C.Yeastract gathers all published regulatory associations and TF-binding sites for Komagataellaphaffii (formerly Pichia pastoris), the oleaginous yeast Yarrowia lipolytica, the lactose fermenting species Kluyveromyces lactis and Kluyveromyces marxianus, and the remarkably weak acid-tolerant food spoilage yeast Zygosaccharomyces bailii. The objective of this review paper is to advertise the update of the existing information since the release of N.C.Yeastract in 2019, and to raise awareness in the community about its potential to help the day-to-day work on these species, exploring all the information available in the global YEASTRACT + portal. Using simple and widely used examples, a guided exploitation is offered for several tools: (i) inference of orthologous genes; (ii) search for putative TF binding sites and (iii) inter-species comparison of transcription regulatory networks and prediction of TF-regulated networks based on documented regulatory associations available in YEASTRACT + for well-studied species. The usage potentialities of the new CommunityYeastract platform by the yeast community are also discussed.
Role of Renal Sympathetic Nerve Activity in Volatile Anesthesia's Effect on Renal Excretory Function
Authors: Taavo Micael , Rundgren Mats , Frykholm Peter , Larsson Anders , Franzén Stephanie , Vargmar Karin , Valarcher Jean F , DiBona Gerald F , Frithiof Robert 
Published: August 2021

Abstract
Regulation of fluid balance is pivotal during surgery and anesthesia and affects patient morbidity, mortality, and hospital length of stay. Retention of sodium and water is known to occur during surgery but the mechanisms are poorly defined. In this study, we explore how the volatile anesthetic sevoflurane influences renal function by affecting renal sympathetic nerve activity (RSNA). Our results demonstrate that sevoflurane induces renal sodium and water retention during pediatric anesthesia in association with elevated plasma concentration of renin but not arginine–vasopressin. The mechanisms are further explored in conscious and anesthetized ewes where we show that RSNA is increased by sevoflurane compared with when conscious. This is accompanied by renal sodium and water retention and decreased renal blood flow (RBF). Finally, we demonstrate that renal denervation normalizes renal excretory function and improves RBF during sevoflurane anesthesia in sheep. Taken together, this study describes a novel role of the renal sympathetic nerves in regulating renal function and blood flow during sevoflurane anesthesia.
Causes and Consequences of Purifying Selection on SARS-CoV-2
Authors: Morales Atahualpa Castillo , Rice Alan M , Ho Alexander T , Mordstein Christine , Mühlhausen Stefanie , Watson Samir , Cano Laura , Young Bethan , Kudla Grzegorz , Hurst Laurence D 
Published: August 2021

Abstract
Owing to a lag between a deleterious mutation’s appearance and its selective removal, gold-standard methods for mutation rate estimation assume no meaningful loss of mutations between parents and offspring. Indeed, from analysis of closely related lineages, in SARS-CoV-2, the Ka/Ks ratio was previously estimated as 1.008, suggesting no within-host selection. By contrast, we find a higher number of observed SNPs at 4-fold degenerate sites than elsewhere and, allowing for the virus’s complex mutational and compositional biases, estimate that the mutation rate is at least 49–67% higher than would be estimated based on the rate of appearance of variants in sampled genomes. Given the high Ka/Ks one might assume that the majority of such intrahost selection is the purging of nonsense mutations. However, we estimate that selection against nonsense mutations accounts for only ∼10% of all the “missing” mutations. Instead, classical protein-level selective filters (against chemically disparate amino acids and those predicted to disrupt protein functionality) account for many missing mutations. It is less obvious why for an intracellular parasite, amino acid cost parameters, notably amino acid decay rate, is also significant. Perhaps most surprisingly, we also find evidence for real-time selection against synonymous mutations that move codon usage away from that of humans. We conclude that there is common intrahost selection on SARS-CoV-2 that acts on nonsense, missense, and possibly synonymous mutations. This has implications for methods of mutation rate estimation, for determining times to common ancestry and the potential for intrahost evolution including vaccine escape.
Patterns and mechanisms of sex ratio distortion in the Collaborative Cross mouse mapping population
Authors: Haines Brett A , Barradale Francesca , Dumont Beth L 
Published: August 2021

Abstract
In species with single-locus, chromosome-based mechanisms of sex determination, the laws of segregation predict an equal ratio of females to males at birth. Here, we show that departures from this Mendelian expectation are commonplace in the 8-way recombinant inbred Collaborative Cross (CC) mouse population. More than one-third of CC strains exhibit significant sex ratio distortion (SRD) at wean, with twice as many male-biased than female-biased strains. We show that these pervasive sex biases persist across multiple breeding environments, are stable over time, and are not mediated by random maternal effects. SRD exhibits a heritable component, but QTL mapping analyses fail to nominate any large effect loci. These findings, combined with the reported absence of sex ratio biases in the CC founder strains, suggest that SRD manifests from multilocus combinations of alleles only uncovered in recombined CC genomes. We explore several potential complex genetic mechanisms for SRD, including allelic interactions leading to sex-biased lethality, genetic sex reversal, chromosome drive mediated by sex-linked selfish elements, and incompatibilities between specific maternal and paternal genotypes. We show that no one mechanism offers a singular explanation for this population-wide SRD. Instead, our data present preliminary evidence for the action of distinct mechanisms of SRD at play in different strains. Taken together, our work exposes the pervasiveness of SRD in the CC population and nominates the CC as a powerful resource for investigating diverse genetic causes of biased sex chromosome transmission.
New insights on water storage dynamics in a mountainous catchment from superconducting gravimetry
Authors: Chaffaut Q , Hinderer J , Masson F , Viville D , Pasquet S , Boy J P , Bernard J D , Lesparre N , Pierret M C 
Published: August 2021

SUMMARY
Assessing the spatial and temporal heterogeneity in subsurface water storage has strong societal and environmental implications, as it is key to assess the water availability for the ecosystem and society. This challenge is especially significant in mountainous areas, where the local population totally depends on springwater as a freshwater resource, while water storage dynamics is complex to evaluate because it exhibits spatiotemporal heterogeneities on all scales as a result of the topography. In this study, we compare the water balance of a headwater granitic catchment (CWB) with water storage changes assessed from in situ continuous gravity monitoring using an iGrav superconducting gravimeter (SGWSC) located at the summit of the catchment. We show that SGWSC and CWB exhibit a similar annual cycle, although they deviate in the months following winter peak flow events. We investigate the reasons for these discrepancies using a tank model adjusted to the SG signal. This shows that during these events, the effective discharge in the SG footprint area is much lower than the catchment streamflow. We attribute this difference in the drainage term to a lower contribution of the upper part of the catchment to the generation of peak flow, compared to the lower part.