bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling the Impact of COVID-19 Mitigation Strategies in Pennsylvania, USA
Authors: Krauland Mary G. , Roberts Mark S. 
Published: June 2024

Purpose. To estimate the impact on mortality of nonpharmaceutical interventions (NPIs) implemented early in the COVID-19 pandemic. Methods. We implemented an agent-based modified SEIR model of COVID-19, calibrated to match death numbers reported in Pennsylvania from January 2020 to April 2021 and including representations of NPIs implemented in Pennsylvania. To investigate the impact of these strategies, we ran the calibrated model with no interventions and with varying combinations, timings, and levels of interventions. Results. The model closely replicated death outcomes data for Pennsylvania. Without NPIs, deaths in the early months of the pandemic were estimated to be much higher (67,718 deaths compared to actual 6,969). Voluntary interventions alone were relatively ineffective at decreasing mortality. Delaying implementation of interventions led to higher deaths (∼9,000 more deaths with just a 1-week delay). School closure was insufficient as a single intervention but was an important part of a combined intervention strategy. Conclusions. NPIs were effective at reducing deaths early in the COVID-19 pandemic. Agent-based models can incorporate substantial detail on infectious disease spread and the impact of mitigations. Policy Implications. The model supports the importance and effectiveness of NPIs to decrease morbidity from respiratory pathogens. This is particularly important for emerging pathogens for which no vaccines or treatments exist, but such strategies are applicable to a variety of respiratory pathogens. Highlights Nonpharmaceutical interventions were used extensively during the early period of the COVID-19 pandemic, but their use has remained controversial. Agent-based modeling of the impact of these mitigation strategies early in the COVID-19 pandemic supports the effectiveness of nonpharmaceutical interventions at decreasing mortality. Since such interventions are not specific to a particular pathogen, they can be used to protect against any respiratory pathogen, known or emerging. They can be applied rapidly when conditions warrant.
Institutional drivers for integrating palliative care services in a hospital in a sub-Saharan African military hospital context
Authors: Boateng Samuel Asamoah , Okyere Joshua , Attafuah Priscilla Y. A. , Dzansi Gladys 
Published: June 2024

Background: The growing burden of life-threatening illnesses and advancements in care interventions call for the intentional integration of palliative care services into existing care systems. The absence of active, functioning palliative care services in most hospitals in Ghana is a major concern. This study explored the factors influencing the integration of palliative care services in one of such institutions. Objectives: The aim of the study was to explore the institutional drivers of palliative care integration in a military health facility. Design: Exploratory qualitative study. Methods: We employed a qualitative exploratory study design situated within a constructivist paradigm. A purposive sampling method was used to select and interview 11 healthcare professionals. A semistructured interview was used to conduct face-to-face, in-depth interviews with participants between April and May 2022. A thematic data analysis was done based on the Braun and Clarke analysis process with the aid of QSR NVivo-12. Results: The six themes that describe the institutional driving factors for integrating palliative care services were cognitive restructuring, supportive logistics and infrastructure, staffing, healthcare professional skills, institutional policies and priorities, and utilization of focal persons. It was observed that a paradigm shift in the mindset of healthcare professionals and administrators was a major driver that would determine the integration of palliative care services. A cognitive restructuring will facilitate a more aggressive integration of palliative care services because logistics, staffing, and medication access will be prioritized. Conclusion: Institutions have the responsibility of aligning with the WHO policy on palliative care service access and must invest in training, staffing, prioritizing palliative care needs and policies, procurement of essential drugs, and the provision of logistics and supportive infrastructure to scale up the implementation of palliative care services.
Rotator Cuff Repair: The Compression SpeedBridge Technique
Authors: Marcaccio Stephen , Godshaw Brian , Arner Justin , Bradley James 
Published: June 2024

Background: While rotator cuff repair has generally produced good to excellent outcomes, re-tear rates remain variable, with rates ranging from 20% to 50%. The ideal rotator cuff repair includes 3 main components: restoration of the humeral footprint contact area, appropriate compression of the tendon to the humeral footprint, and minimal motion at the bone-tendon interface until bone-tendon healing is completed. This video takes a well-established knotless double-row technique for rotator cuff repair and augments it with a modification to promote additional compression of the medial row tendon to the humeral footprint. Indications: This compression SpeedBridge technique is indicated for repair of T-type rotator cuff tears involving the supraspinatus and infraspinatus tendons in patients that have failed conservative management, including physical therapy, activity modification, and corticosteroid injections. This technique can also be applied to U-shaped or L-shaped tears by removing the initial step, which involves side-to-side repair of the “T” portion of the T-type tear. Of note, findings such as advanced muscle atrophy (Goutalier III/IV) and advanced glenohumeral arthritis are concerning for irreparable tears and may be contraindications for surgical repair. Technique Description: With the patient in the lateral decubitus position, a diagnostic arthroscopy is performed, the rotator cuff tear is debrided, and the footprint prepared. Two side-to-side stitches are placed to repair the “T” portion of the tear. The medial row anchors are then sequentially placed, and the pre-loaded sutures are passed through the tendon in 4 sequential locations in specific fashion. After placement of looped sutures in the anterior and posterior rotator cables, the passed sutures are then incorporated into the lateral row anchors. The medial row compression is provided by shuttling previously placed compression stitches through the knotless mechanism in the medial row anchors and terminally tensioned. Results: This technique provides additional medial row compression to an already-established knotless double-row rotator cuff repair technique to facilitate improved bone-tendon healing and construct strength. Discussion/Conclusion: The compression SpeedBridge technique is a unique method to apply additional medial row compression to a double-row rotator cuff repair. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Murine models of erythroid 5ALA synthesis disorders and their conditional synthetic lethal dependency on pyridoxine
Authors: Ducamp Sarah , Sendamarai Anoop K. , Campagna Dean R. , Chin Desmond Wai Loon , Fujiwara Yuko , Schmidt Paul J. , Fleming Mark D. 
Published: June 2024

Abstract
X-linked sideroblastic anemia (XLSA) and X-linked protoporphyria (XLPP) are uncommon diseases caused by loss-of-function and gain-of-function mutations, respectively, in the erythroid form of 5-aminolevulinic acid synthetase (ALAS), ALAS2, which encodes the first enzyme in heme biosynthesis. A related congenital sideroblastic anemia (CSA) is due to mutations in SLC25A38 (solute carrier family 25 member A38), which supplies mitochondrial glycine for ALAS2 (SLC25A38–CSA). The lack of viable animal models has limited the studies on pathophysiology and development of therapies for these conditions. Here, using CRISPR-CAS9 gene editing technology, we have generated knockin mouse models that recapitulate the main features of XLSA and XLPP; and using conventional conditional gene targeting in embryonic stem cells, we also developed a faithful model of the SLC25A38-CSA. In addition to examining the phenotypes and natural history of each disease, we determine the effect of restriction or supplementation of dietary pyridoxine (vitamin B6), the essential cofactor of ALAS2, on the anemia and porphyria. In addition to the well-documented response of XLSA mutations to pyridoxine supplementation, we also demonstrate the relative insensitivity of the XLPP/EPP protoporphyrias, severe sensitivity of the XLSA models, and an extreme hypersensitivity of the SLC25A38-CSA model to pyridoxine deficiency, a phenotype that is not shared with another mouse hereditary anemia model, Hbbth3/+ β-thalassemia intermedia. Thus, in addition to generating animal models useful for examining the pathophysiology and treatment of these diseases, we have uncovered an unsuspected conditional synthetic lethality between the heme synthesis–related CSAs and pyridoxine deficiency. These findings have the potential to inform novel therapeutic paradigms for the treatment of these diseases.
Impact of elexacaftor/tezacaftor/ivacaftor therapy on lung clearance index and magnetic resonance imaging in children with cystic fibrosis and one or twoF508delalleles
Authors: Stahl Mirjam , Dohna Martha , Graeber Simon Y. , Sommerburg Olaf , Renz Diane M. , Pallenberg Sophia T. , Voskrebenzev Andreas , Schütz Katharina , Hansen Gesine , Doellinger Felix , Steinke Eva , Thee Stephanie , Röhmel Jobst , Barth Sandra , Rückes-Nilges Claudia , Berges Julian , Hämmerling Susanne , Wielpütz Mark O. , Naehrlich Lutz , Vogel-Claussen Jens , Tümmler Burkhard , Mall Marcus A. , Dittrich Anna-Maria 
Published: June 2024

BackgroundWe recently demonstrated that elexacaftor/tezacaftor/ivacaftor (ETI) improves the lung clearance index (LCI) and abnormalities in lung morphology detected by magnetic resonance imaging (MRI) in adolescent and adult patients with cystic fibrosis (CF). However, real-world data on the effect of ETI on these sensitive outcomes of lung structure and function in school-age children with CF have not been reported. The aim of this study was therefore to examine the effect of ETI on the LCI and the lung MRI score in children aged 6–11 years with CF and one or twoF508delalleles.MethodsThis prospective, observational, multicentre, post-approval study assessed the longitudinal LCI up to 12 months and the lung MRI score before and 3 months after initiation of ETI.ResultsA total of 107 children with CF including 40 heterozygous forF508deland a minimal function mutation (F/MF) and 67 homozygous forF508del(F/F) were enrolled in this study. Treatment with ETI improved the median (interquartile range (IQR)) LCI in F/MF (−1.0 (−2.0– −0.1); p<0.01) and F/F children (−0.8 (−1.9– −0.2); p<0.001) from 3 months onwards. Further, ETI improved the median (IQR) MRI global score in F/MF (−4.0 (−9.0–0.0); p<0.01) and F/F children (−3.5 (−7.3– −0.8); p<0.001).ConclusionsETI improves early abnormalities in lung ventilation and morphology in school-age children with CF and at least oneF508delallele in a real-world setting. Our results support early initiation of ETI to reduce or even prevent lung disease progression in school-age children with CF.
Global herpes zoster burden in adults with asthma: a systematic review and meta-analysis
Authors: Mortimer Kevin J. , Cruz Alvaro A. , Sepúlveda-Pachón Ingrid T. , Jorga Anamaria , Vroling Hilde , Williams Charles 
Published: June 2024

BackgroundAsthma is a common respiratory disease, which may be associated with an increased risk of herpes zoster (HZ), often a debilitating disease associated with severe pain. This is the first systematic review with the objective of summarising evidence on HZ burden in adults with asthma.MethodsA global systematic literature review and meta-analysis was conducted (MEDLINE and Embase, 2003–2024) on HZ burden (incidence, risk and complications) in adults (≥18 years) with asthma.ResultsThere were 19 studies included on HZ outcomes in adults with asthma. Pooled HZ incidence per 1000 person-years was 5.71 (95% CI 4.68–6.96) in adults aged ≥18 years (4.20 (95% CI 3.09–5.70) in those aged <60 yearsversus10.33 (95% CI 9.17–11.64) in those aged ≥60 years). The pooled rate ratio for developing HZ was 1.23 (95% CI 1.11–1.35) in those aged ≥18 years and 1.36 (95% CI 1.15–1.61) in those aged ≥50 years. The risk of HZ was higher in people with asthma using systemic corticosteroids, long-acting β-agonists plus inhaled corticosteroids and “add-on therapy”. Asthma was also associated with an increased risk of post-herpetic neuralgia (OR 1.21, 95% CI 1.06–1.37) and HZ ophthalmicus (OR 1.9, 95% CI 1.1–3.2). Differences in study design, setting, case definitions and follow-up durations led to heterogeneity.ConclusionsThis systematic literature review and meta-analysis found that adults with asthma have an increased risk of HZ, with higher risks in older age groups and in those on certain treatments, such as oral corticosteroids. HZ vaccines are available for adults, including those with comorbidities such as asthma, and can be considered as part of integrated respiratory care.
Epigenomic partitioning of a polygenic risk score for asthma reveals distinct genetically driven disease pathways
Authors: Stikker Bernard , Trap Lianne , Sedaghati-Khayat Bahar , de Bruijn Marjolein J.W. , van Ijcken Wilfred F.J. , de Roos Emmely , Ikram Arfan , Hendriks Rudi W. , Brusselle Guy , van Rooij Jeroen , Stadhouders Ralph 
Published: June 2024

BackgroundIndividual differences in susceptibility to developing asthma, a heterogeneous chronic inflammatory lung disease, are poorly understood. Whether genetics can predict asthma risk and how genetic variants modulate the complex pathophysiology of asthma are still debated.AimTo build polygenic risk scores for asthma risk prediction and epigenomically link predictive genetic variants to pathophysiological mechanisms.MethodsRestricted polygenic risk scores were constructed using single nucleotide variants derived from genome-wide association studies and validated using data generated in the Rotterdam Study, a Dutch prospective cohort of 14 926 individuals. Outcomes used were asthma, childhood-onset asthma, adulthood-onset asthma, eosinophilic asthma and asthma exacerbations. Genome-wide chromatin analysis data from 19 disease-relevant cell types were used for epigenomic polygenic risk score partitioning.ResultsThe polygenic risk scores obtained predicted asthma and related outcomes, with the strongest associations observed for childhood-onset asthma (2.55 odds ratios per polygenic risk score standard deviation, area under the curve of 0.760). Polygenic risk scores allowed for the classification of individuals into high-risk and low-risk groups. Polygenic risk score partitioning using epigenomic profiles identified five clusters of variants within putative gene regulatory regions linked to specific asthma-relevant cells, genes and biological pathways.ConclusionsPolygenic risk scores were associated with asthma(-related traits) in a Dutch prospective cohort, with substantially higher predictive power observed for childhood-onset than adult-onset asthma. Importantly, polygenic risk score variants could be epigenomically partitioned into clusters of regulatory variants with different pathophysiological association patterns and effect estimates, which likely represent distinct genetically driven disease pathways. Our findings have potential implications for personalised risk mitigation and treatment strategies.
High-flow humidified oxygen as an early intervention in children with acute severe asthma: a feasibility randomised controlled trial
Authors: Kapur Akshat , Rojas-Anaya Héctor , Roberts Graham , Roland Damian , Gupta Atul , Lazner Michaela , Bayreuther Jane , Cantle Fleur , Jones Christina , Pappachan John , Bremner Stephen , James David , Fitzgerald Shane , Owens Kelly , Asim Lalarukh , Khaleva Ekaterina , Seddon Paul 
Published: June 2024

BackgroundTreating children with acute severe asthma (ASA) who fail to respond to first-line inhaled bronchodilators is problematic: use of intravenous agents is inconsistent and side-effects are common. High-flow humidified oxygen (HiFlo) has shown promise in other respiratory conditions and is increasingly used in ASA, but with little evidence.MethodsWe conducted a feasibility randomised controlled trial with deferred consent to assess early HiFlo in children aged 2–11 years with ASA not responding to “burst” therapy (high-dose inhaled salbutamol ± ipratropium). Children with Paediatric Respiratory Assessment Measure (PRAM) score 5+ after “burst” were randomised to commence HiFlo or follow standard care. Candidate primary outcomes assessed were treatment failure requiring escalation, and time to meeting hospital discharge criteria.ResultsThe target was met despite coronavirus disease 2019 pandemic disruption: 56 children were randomised across four sites, with deferred consent received in 50 out of 56 (89%), and mean recruitment rate 1.1 per site per month. 28 were allocated early HiFlo and 22 standard care. Data collection was complete for both candidate primary outcomes. Treatment failure requiring escalation occurred in 18 of 28 children (64%) in the HiFlo arm and in 19 of 22 (86%) in the standard care arm. Median (interquartile range) time from randomisation to meeting discharge criteria was 29.3 h (21.8–43.7 h) in the HiFlo arm and 36.8 h (24.1–46.3 h) in the standard care arm.ConclusionsHiFlo in childhood ASA is a potentially promising intervention whose use is increasing despite lack of evidence. A definitive randomised controlled trial to assess its effectiveness is required and appears to be feasible.
Provocation of attacks to discover migraine signaling mechanisms and new drug targets: early history and future perspectives - a narrative review
Authors: Olesen Jes 
Published: June 2024

Abstract
Introduction
The development of several experimental migraine provocation models has significantly contributed to an understanding of the signaling mechanisms of migraine. The early history of this development and a view to the future are presented as viewed by the inventor of the models.

Methods
Extensive knowledge of the literature was supplemented by scrutiny of reference lists.

Results
Early studies used methodologies that were not blinded. They suggested that histamine and nitroglycerin (Glyceryl trinitrate, GTN) could induce headache and perhaps migraine. The development of a double blind, placebo-controlled model, and the use of explicit diagnostic criteria for induced migraine was a major step forward. GTN, donor of nitric oxide (NO), induced headache in people with- and without migraine as well as delayed migraine attacks in those with migraine. Calcitonin gene-related peptide (CGRP) did the same, supporting the development of CGRP antagonists now widely used in patients. Likewise, pituitary adenylate cyclase activating peptide (PACAP) provoked headache and migraine. Recently a PACAP antibody has shown anti migraine activity in a phase 2 trial. Increase of second messengers activated by NO, CGRP and PACAP effectively induced migraine. The experimental models have also been used in other types of headaches and have been combined with imaging and biochemical studies. They have also been used for drug testing and in genetic studies.

Conclusion
Conclusion. Human migraine provocation models have informed about signaling mechanisms of migraine leading to new drugs and drug targets. Future use of these models in imaging-, biochemistry- and genetic studies as well as in the further study of animal models is promising.
Effects of edaravone dexborneol on functional outcome and inflammatory response in patients with acute ischemic stroke
Authors: Chen Wenxia , Zhang Hanqing , Li Zhenzhen , Deng Qiwen , Wang Meng , Chen Yingbin , Zhang Yuan 
Published: June 2024

Abstract
Background
Edaravone dexborneol has been reported as an effective neuroprotective agent in the treatment of acute ischemic stroke (AIS). This study aimed at investigating the impact of edaravone dexborneol on functional outcomes and systematic inflammatory response in AIS patient.

Methods
All participants were recruited from the AISRNA study (registered 21/11/2019, NCT04175691 [ClinicalTrials.gov]) between January 2022 and December 2022. The AIS patients were divided into two groups based on whether they received the treatment of edaravone dexborneol (37.5 mg/12 hours, IV) within 48 h after stroke onset. Inflammatory response was determined by detecting levels of cytokines (interleukin-2 [IL-2], IL-4, IL-5, IL-8, IL-6, IL-10, IL-12p70, IL-17, tumor necrosis factor-α [TNF-α], interferon-γ [IFN-γ], IFN-α, and IL-1β) within 14 days after stroke onset.

Results
Eighty-five AIS patients were included from the AISRNA study. Patients treated with edaravone dexborneol showed a significantly higher proportion of modified Rankin Scale score < 2 compared to those who did not receive this treatment (70.7% versus 47.8%; P = 0.031). Furthermore, individuals receiving edaravone dexborneol injection exhibited lower expression levels of interleukin (IL)-1β, IL-6, and IL-17, along with higher levels of IL-4 and IL-10 expression during the acute phase of ischemic stroke (P < 0.05). These trends were not observed for IL-2, IL-5, IL-8, IL-12p70, tumor necrosis factor-α, interferon-γ [IFN-γ], and IFN-α (P > 0.05).

Conclusions
Treatment with edaravone dexborneol resulted in a favorable functional outcome at 90 days post-stroke onset when compared to patients without this intervention; it also suppressed proinflammatory factors expression while increasing anti-inflammatory factors levels.

Trial registration
ClinicalTrials.gov NCT04175691. Registered November 21, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04175691.
Relationship of urinary glyphosate concentrations with glycosylated hemoglobin and diabetes in US adults: a cross-sectional study
Authors: Tang Peng , Wang Yican , Liao Qian , Zhou Yong , Huang Huishen , Liang Jun , Zeng Xiaoyun , Qiu Xiaoqiang 
Published: June 2024

Abstract
Background
Glyphosate is a commonly used herbicide worldwide and is purportedly associated with multiple health effects. Research assessing the association of glyphosate concentrations with glycosylated hemoglobin (HbA1c) levels and the prevalence of diabetes is scarce. We sought to evaluate the association between urinary glyphosate levels and HbA1c levels and the prevalence of diabetes.

Methods
A total of 2,745 adults in the National Health and Nutrition Examination Survey from 2013 to 2016 were included in this study. Generalized linear models (GLM) were applied to evaluate the associations of glyphosate concentrations with HbA1c levels and the prevalence of diabetes. The dose–response relationship was examined using restricted cubic splines (RCS).

Results
Significantly positive correlations of urinary glyphosate concentrations with HbA1c levels (percentage change: 1.45; 95% CI: 0.95, 1.96; P < 0.001) and the prevalence of diabetes (OR: 1.45; 95% CI: 1.24, 1.68; P < 0.001) were found after adjustment. Compared with the lowest quartile of glyphosate levels, the highest quartile was positively associated with HbA1c levels (percentage change: 4.19; 95% CI: 2.54, 5.85; P < 0.001) and the prevalence of diabetes (OR: 1.89; 95% CI: 1.37, 2.63; P < 0.001). The RCS curves demonstrated a monotonically increasing dose–response relationship between urinary glyphosate levels and the prevalence of diabetes and HbA1c levels.

Conclusions
Urinary glyphosate concentrations are positively associated with HBA1c levels and the prevalence of diabetes. To verify our findings, additional large-scale prospective investigations are required.