bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiology-guided quantitative symptom analysis for gastroduodenal disorders
Authors: Schamberg Gabriel , Varghese Chris , Uren Emma , Calder Stefan , O’Grady Greg , Gharibans Armen A 
Published: June 2023

AbstractBackgroundCurrent approaches to symptom-based classifications in gastroduodenal disorders are binary and substantially overlapping. We aimed to develop a standardized and quantitative system for classifying patient-level symptom profiles guided on physiological principles.MethodsA large database (n = 787) of 4.5 h (30 min baseline; 4-h postprandial) Gastric Alimetry™ (Alimetry, NZ) recordings were used to identify, and quantify distinct symptom patterns based on established gastroduodenal physiology concepts. Tests comprised a standardized meal challenge and symptoms were simultaneously recorded at minimum 15 minute intervals using a 10-point likert scale with pictograms encoded in a validated digital App.Key ResultsSix symptom profiles were defined. The meal change metric was used to define ‘meal-induced’ and ‘meal-relieved’ symptom profiles, defined as an increase (+2) or decrease (−2) in the average symptom severity between the first post- and pre-prandial hours of recordings. The continuous profile was defined as a reduced range (<3; i.e., difference between the 95th and 5th percentile symptom severity), and thresholded to the 5th percentile of symptom severity being > 2. The symptom/amplitude correlation metric defined the ‘sensorimotor’ profile, thresholded when the correlation was >0.5. The symptom/amplitude time lag metric was used to define ‘activity-relieved’ and ‘post-gastric’ symptom profiles, defined as negative (< -0.25) or positive (>0.25) average difference between the cumulative distribution functions of the symptom and amplitude curves.Conclusions & InferencesStandardized quantification of symptom profiles in relation to a meal-stimulus and gastric amplitude offer a novel classification scheme based on gastroduodenal physiology.
In-hospital Outcomes of Septal Myectomy Versus Alcohol Septal Ablation for Hypertrophic Cardiomyopathy with Outflow Tract Obstruction - An Update and Insights from The National Inpatient Sample from 2011-2019
Authors: Inestroza Karla , Mijares-Rojas Ivan , Matute-Martínez Carlos , Ergui Ian , Albosta Michael , Vergara-Sanchez Carlos , Dangl Michael , Hernandez Rafael Jaciel , Ebner Bertrand , Vincent Louis T , Grant Jelani , Maning Jennifer , Alfonso Carlos , Colombo Rosario 
Published: June 2023

AbstractBackgroundSeptal Myectomy (SM) and Alcohol Septal Ablation (ASA) improve symptoms in patients with Hypertrophic Cardiomyopathy with outflow tract obstruction (oHCM). However, outcomes data in this population is predominantly from specialized centers.MethodsThe National Inpatient Database was queried from 2011- 2019 for relevant ICD-9 and −10 diagnostic and procedural codes. We compared baseline characteristics and in-hospital outcomes of patients with oHCM who underwent SM vs. ASA. A p-value <0.001 was considered statistically significant.ResultsWe identified 17,245 patients with oHCM who underwent septal reduction therapies, of whom 62.5% underwent SM, and 37.5% underwent ASA. Patients who underwent SM had higher all-cause mortality (OR:2.2 [1.7-2.9]), post-procedure ischemic stroke (OR: 2.4 [1.8-3.2]), acute kidney injury (OR: 1.9 [1.7-2.2]), vascular complications (OR: 4 [2.8-5.7]), ventricular septal defect (OR: 4.6 [3.5-6.1]), cardiogenic shock (OR: 2 [1.5-2.6]), sepsis (OR: 5.2 [3.3-8.1]), and left bundle branch block (OR: 3.2 [2.8-3.7]), compared to ASA. Patients who underwent ASA had higher post-procedure complete heart block (OR: 1.2 [1.1-1.4]), 2nd-degree AV Block (OR: 2 [1.4-3]), right bundle branch block (OR: 6.4 [5.3-7.8]), ventricular tachycardia (OR:2 [1.8-2.3]), supraventricular tachycardia (OR: 1.4 [1.2-1.7]), and more commonly required pacemaker (OR: 1.4 [1.2-1.6]) or implantable cardioverter-defibrillator insertion (OR: 1.3 [1.1-1.5]) (p<0.001 for all) compared to SM.ConclusionsThis nationwide analysis evidenced that patients undergoing SM had higher in-hospital mortality and periprocedural complications than ASA; however, those undergoing ASA had more post-procedure conduction abnormalities and pacemaker or ICD implantation. The implications of these findings warrant further investigation regarding patient selection strategies for these therapies.
Bioenergetic function is decreased in peripheral blood mononuclear cells of veterans with Gulf War Illness
Authors: Meyer Joel N , Pan William K , Ryde Ian T , Alexander Thomas , Klein-Adams Jacquelyn C. , Ndirangu Duncan S. , Falvo Michael J 
Published: June 2023

AbstractGulf War Illness (GWI) is a major health problem for approximately 250,000 Gulf War (GW) veterans, but the etiology of GWI is unclear. We hypothesized that mitochondrial dysfunction is an important contributor to GWI, based on the similarity of some GWI symptoms to those occurring in some mitochondrial diseases; the plausibility that certain pollutants to which GW veterans were exposed affect mitochondria; mitochondrial effects observed in studies in laboratory models of GWI; and previous evidence of mitochondrial outcomes in studies in GW veterans. A primary role of mitochondria is generation of energy via oxidative phosphorylation. However, direct assessment of mitochondrial respiration, reflecting oxidative phosphorylation, has not been carried out in veterans with GWI. In this case-control observational study, we tested multiple measures of mitochondrial function and integrity in a cohort of 114 GW veterans, 80 with and 34 without GWI as assessed by the Kansas definition. In circulating white blood cells, we analyzed multiple measures of mitochondrial respiration and extracellular acidification, a proxy for non-aerobic energy generation; mitochondrial DNA (mtDNA) copy number; mtDNA damage; and nuclear DNA damage. We also collected detailed survey data on demographics; deployment; self-reported exposure to pesticides, pyridostigmine bromide, and chemical and biological warfare agents; and current biometrics, health and activity levels. We observed a 9% increase in mtDNA content in blood in veterans with GWI, but did not detect differences in DNA damage. Basal and ATP-linked oxygen consumption were respectively 42% and 47% higher in veterans without GWI, after adjustment for mtDNA amount. We did not find evidence for a compensatory increase in anaerobic energy generation: extracellular acidification was also lower in GWI (12% lower at baseline). A subset of 27 and 26 veterans returned for second and third visits, allowing us to measure stability of mitochondrial parameters over time. mtDNA CN, mtDNA damage, ATP-linked OCR, and spare respiratory capacity were moderately replicable over time, with intraclass correlation coefficients of 0.43, 0.44, 0.50, and 0.57, respectively. Other measures showed higher visit- to-visit variability. Many measurements showed lower replicability over time among veterans with GWI compared to veterans without GWI. Finally, we found a strong association between recalled exposure to pesticides, pyridostigmine bromide, and chemical and biological warfare agents and GWI (p < 0.01, p < 0.01, and p < 0.0001, respectively). Our results demonstrate decreased mitochondrial respiratory function as well as decreased glycolytic activity, both of which are consistent with decreased energy availability, in peripheral blood mononuclear cells in veterans with GWI.
Impact of COVID-19 Pandemic on Sleep Including HRV and Physical Activity as Mediators: A Causal ML Approach
Authors: Khatibi Elahe , Abbasian Mahyar , Azimi Iman , Labbaf Sina , Feli Mohammad , Borelli Jessica , Dutt Nikil , Rahmani Amir M. 
Published: June 2023

AbstractSleep quality is crucial to both mental and physical well-being. The COVID-19 pandemic, which has notably affected the population’s health worldwide, has been shown to deteriorate people’s sleep quality. Numerous studies have been conducted to evaluate the impact of the COVID-19 pandemic on sleep efficiency, investigating their relationships using correlation-based methods. These methods merely rely on learning spurious correlation rather than the causal relations among variables. Furthermore, they fail to pinpoint potential sources of bias and mediators and envision counterfactual scenarios, leading to a poor estimation. In this paper, we develop a Causal Machine Learning method, which encompasses causal discovery and causal inference components, to extract the causal relations between the COVID-19 pandemic (treatment variable) and sleep quality (outcome) and estimate the causal treatment effect, respectively. We conducted a wearable-based health monitoring study to collect data, including sleep quality, physical activity, and Heart Rate Variability (HRV) from college students before and after the COVID-19 lockdown in March 2020. Our causal discovery component generates a causal graph and pinpoints mediators in the causal model. We incorporate the strongly contributing mediators (i.e., HRV and physical activity) into our causal inference component to estimate the robust, accurate, and explainable causal effect of the pandemic on sleep quality. Finally, we validate our estimation via three refutation analysis techniques. Our experimental results indicate that the pandemic exacerbates college students’ sleep scores by 8%. Our validation results show significant p-values confirming our estimation.
Nothing without connection” – participant perspectives and experiences of mentorship in capacity building in Timor-Leste
Authors: Yan Jennifer , Martins Nelson , Amaral Salvador , Francis Joshua R , Kameniar Barbara , Delany Clare 
Published: June 2023

AbstractBackgroundThe literature on mentorship approaches to capacity building in global health is limited. Likewise, there are few qualitative studies that describe mentorship in capacity building in global health from the perspective of the mentors and mentees.MethodsThis qualitative study examined the perspectives and experiences of participants involved in a program of health capacity building in Timor-Leste that was based on a side-by-side, in-country mentorship approach. Semi-structured interviews were conducted with 23 participants (including Timorese and Australian mentors, and local Timorese counterparts) from across a range of professional health disciplines, followed by a series of member checking workshops. Findings were reviewed using inductive thematic analysis. Participants were included in review and refinement of themes.ResultsFour major themes were identified: the importance of trust and connection within the mentoring relationship itself; the side-by-side nature of the relationship (akompaña); mentoring in the context of external environmental challenges; and the need for the mentoring relationship to be dynamic and evolving, and aligned to a shared vision and shared goals.DiscussionThe importance of accompaniment (akompaña) as a key element of the mentoring relationship requires further exploration and study. Many activities in global health capacity building remain focused on provision of training, supervision, and supportive supervision of competent task performance. Viewed through a decolonising lens, there is an imperative for global health actors to align with local priorities and goals, and work alongside individuals supporting them in their vision to become independent leaders of their professions. We propose that placing mentoring relationships at the centre of human resource capacity building programs encourages deep and transformative learning, and is more likely to lead to long term, meaningful and sustainable change.
Ventilation heterogeneity is increased in adults exposed to coal mine fire-related PM2.5
Authors: McCrabb Thomas , Borg Brigitte , Gao Caroline X. , Smith Catherine , Brown David , Ikin Jillian , Makar Annie , Lane Tyler , Abramson Michael J. , Thompson Bruce R 
Published: June 2023

AbstractBackground and ObjectivesThe Hazelwood Health Study was set up to study long term health effects of a mine fire that blanketed residents of the Latrobe Valley with smoke for 45 days in 2014. The Respiratory Stream specifically assessed the impact of fine particulate matter <2.5μm diameter (PM2.5) exposure from mine fire smoke on lung health. The multiple breath nitrogen washout (MBW) test assesses ventilation heterogeneity, which may detect early airways dysfunction not identified using standard tests such as spirometry. This analysis assessed the association of PM2.5exposure with measures of ventilation heterogeneity.MethodsExposed (Morwell) and unexposed (Sale) participants were recruited 3.5-4 years after the fire from those who had participated in an Adult Survey. MBW was performed to measure lung clearance index (LCI), functional residual capacity (FRC), acinar (Sacin) and conductive (Scond) ventilation heterogeneity. PM2.5exposure was estimated with emission and chemical transport models. Multivariate linear regression models were fitted controlling for confounders.ResultsWe recruited 519 participants. MBW tests were conducted on 504 participants with 479 acceptable test results (40% male; 313 exposed, 166 unexposed). Exposure to mine fire-related PM2.5was associated with increasing Scond (β=2.15/kL, 95%CI: 0.67-3.63, p=0.006), which was comparable to the estimated effect on Scond of 7.9 years of aging. No other MBW outcomes were significant.ConclusionsIncreasing exposure to PM2.5was associated with increased ventilation heterogeneity in the conductive region of the lungs 4 years after the event.
Achieving behavior change at scale: Causal evidence from a national lifestyle intervention program for pre-diabetes in the UK
Authors: Lemp Julia M. , Bommer Christian , Xie Min , Jani Anant , Davies Justine I. , Bärnighausen Till , Vollmer Sebastian , Geldsetzer Pascal 
Published: June 2023

AbstractThere remains widespread doubt among clinicians that mere lifestyle advice and counseling provided in routine care can achieve improvements in health. We aimed to determine the health effects of the largest behavior change program for pre-diabetes globally (the English Diabetes Prevention Programme) when implemented at scale in routine care. We exploited the threshold in glycated hemoglobin (HbA1c) used to decide on program eligibility by applying a regression discontinuity design, one of the most credible quasi-experimental strategies for causal inference, to electronic health data from approximately one-fifth of all primary care practices in England. Program referral led to significant improvements in patients’ HbA1c and body mass index. This analysis provides causal, rather than associational, evidence that lifestyle advice and counseling implemented in a national health system can achieve important health improvements.
Targeting multiphosphorylated tau: technical and clinical validation of a new Simoa® assay for CSF and plasma detection of tau simultaneously phosphorylated at T181 and T231
Authors: Wojdała Anna Lidia , Bellomo Giovanni , Gaetani Lorenzo , Shan Dandan , Parnetti Lucilla , Chiasserini Davide 
Published: June 2023

AbstractBackground and ObjectivesDifferent forms of phosphorylated tau (p-tau) have shown high potential as Alzheimer’s Disease (AD) biomarkers in both cerebrospinal fluid (CSF) and plasma. Hence, we hypothesized that tau peptides showing concomitant phosphorylation at two different sites may provide an increased diagnostic value. We therefore developed and validated a new Simoa® immunoassay detecting tau simultaneously phosphorylated at T181 and T231 (C231D181) in cerebrospinal fluid (CSF) and plasma.MethodsTechnical validation of the C231D181 Simoa® assay included standard curve development, assessment of antibodies cross-reactivity, dilutional linearity, sensitivity, as well as intra- and inter-assay precision. Subsequently, we measured CSF C231D181, p-tau181, and p-tau231 in two cohorts: discovery (MCI-AD n=21, AD dementia n=19, CTRL n=15) and validation (preclinical AD n=19, MCI-AD n=20, AD dementia n=16, frontotemporal dementia n=39, CTRL n=24). Additionally, in the discovery cohort, C231D181, p-tau181, and p-tau231 levels were measured in matched plasma samples.ResultsSpecificity of the assay was assessed using a synthetic peptide simultaneously phosphorylated at T181 and T231, while cross-reactivity was excluded with a mix of single-site phosphorylated peptides (T181 or T231). Both in discovery and validation cohorts, CSF C231D181, p-tau181, and p-tau231 levels were significantly elevated in all AD groups vs. CTRL. As assessed in discovery cohort, plasma p-tau231 and p-tau181 levels enabled effective discrimination of AD continuum groups from CTRL (AUC plasma p-tau231: CTRL vs. MCI-AD=0.925, CTRL vs. AD-dem=0.947; AUC plasma p-tau181: CTRL vs. MCI-AD=0.877, CTRL vs. AD-dem=0.943) while plasma C231D181 did not change among clinical groups.DiscussionA new ultrasensitive immunoassay detecting tau simultaneously phosphorylated at T181 and T231 was developed and validated. While we found this phosphorylated tau form to be significantly elevated across the AD continuum in CSF, in plasma it did not show changes among the diagnostic groups. The differences between CSF and plasma suggest matrix-specific protein processing. Our findings support evidence for qualitative and quantitative importance of tau phosphorylation across AD continuum and warrant further investigation, including assessment of tau simultaneously phosphorylated at multiple sites.
Poor immunogenicity upon SARS-CoV-2 mRNA vaccinations in autoimmune SLE patients is associated with pronounced EF-mediated responses and anti-BAFF/Belimumab treatment
Authors: Faliti Caterina E. , Anam Fabliha A. , Cheedarla Narayanaiah , Woodruff Matthew C. , Usman Sabeena Y. , Runnstrom Martin C. , Van Trinh T.P. , Kyu Shuya , Ahmed Hasan , Morrison-Porter Andrea , Quehl Hannah , Haddad Natalie S. , Chen Weirong , Cheedarla Suneethamma , Neish Andrew S. , Roback John D. , Antia Rustom , Khosroshahi Arezou , Lee F. Eun-Hyung , Sanz Ignacio 
Published: June 2023

AbstractNovel mRNA vaccines have resulted in a reduced number of SARS-CoV-2 infections and hospitalizations. Yet, there is a paucity of studies regarding their effectiveness on immunocompromised autoimmune subjects. In this study, we enrolled subjects naïve to SARS-CoV-2 infections from two cohorts of healthy donors (HD, n=56) and systemic lupus erythematosus (SLE, n=69). Serological assessments of their circulating antibodies revealed a significant reduction of potency and breadth of neutralization in the SLE group, only partially rescued by a 3rdbooster dose. Immunological memory responses in the SLE cohort were characterized by a reduced magnitude of spike-reactive B and T cell responses that were strongly associated with poor seroconversion.Vaccinated SLE subjects were defined by a distinct expansion and persistence of a DN2 spike-reactive memory B cell pool and a contraction of spike-specific memory cTfh cells, contrasting with the sustained germinal center (GC)-driven activity mediated by mRNA vaccination in the healthy population. Among the SLE-associated factors that dampened the vaccine responses, treatment with the monoclonal antibody anti-BAFF/Belimumab (a lupus FDA-approved B cell targeting agent) profoundly affected the vaccine responsiveness by restricting thede novoB cell responses and promoting stronger extra-follicular (EF)-mediated responses that were associated with poor immunogenicity and impaired immunological memory.In summary, this study interrogates antigen-specific responses and characterized the immune cell landscape associated with mRNA vaccination in SLE. The identification of factors associated with reduced vaccine efficacy illustrates the impact of SLE B cell biology on mRNA vaccine responses and provides guidance for the management of boosters and recall vaccinations in SLE patients according to their disease endotype and modality of treatment.
Loneliness Forecasting Using Multi-modal Wearable and Mobile Sensing in Everyday Settings
Authors: Yang Zhongqi , Azimi Iman , Jafarlou Salar , Labbaf Sina , Borelli Jessica , Dutt Nikil , Rahmani Amir M. 
Published: June 2023

AbstractThe adverse effects of loneliness on both physical and mental well-being are profound. Although previous research has utilized mobile sensing techniques to detect mental health issues, few studies have utilized state-of-the-art wearable devices to forecast loneliness and comprehend the physiological manifestations of loneliness and its predictive nature. The primary objective of this study is to examine the feasibility of forecasting loneliness by employing wearable devices, such as smart rings and watches, to monitor early physiological indicators of loneliness. Furthermore, smartphones are employed to capture initial behavioral signs of loneliness. To accomplish this, we employed personalized machine learning techniques, leveraging a comprehensive dataset comprising physiological and behavioral information obtained during our study involving the monitoring of college students. Through the development of personalized models, we achieved a notable accuracy of 0.82 and an F-1 score of 0.82 in forecasting loneliness levels seven days in advance. Additionally, the application of Shapley values facilitated model explainability. The wealth of data provided by this study, coupled with the forecasting methodology employed, possesses the potential to augment interventions and facilitate the early identification of loneliness within populations at risk.
Evaluating Genomic Polygenic Risk Scores for Childhood Acute Lymphoblastic Leukemia in Latinos
Authors: Jeon Soyoung , Lo Ying Chu , Morimoto Libby M. , Metayer Catherine , Ma Xiaomei , Wiemels Joseph L. , de Smith Adam J. , Chiang Charleston W.K. 
Published: June 2023

ABSTRACTThe utility of polygenic risk score (PRS) models has not been comprehensively evaluated for childhood acute lymphoblastic leukemia (ALL), the most common type of cancer in children. Previous PRS models for ALL were based on significant loci observed in genome-wide association studies (GWAS), even though genomic PRS models have been shown to improve prediction performance for a number of complex diseases. In the United States, Latino (LAT) children have the highest risk of ALL, but the transferability of PRS models to LAT children has not been studied. In this study we constructed and evaluated genomic PRS models based on either non-Latino white (NLW) GWAS or a multi-ancestry GWAS. We found that the best PRS models performed similarly between held-out NLW and LAT samples (PseudoR2= 0.086 ± 0.023 in NLW vs. 0.060 ± 0.020 in LAT), and can be improved for LAT if we performed GWAS in LAT-only (PseudoR2= 0.116 ± 0.026) or multi-ancestry samples (PseudoR2= 0.131 ± 0.025). However, the best genomic models currently do not have better prediction accuracy than a conventional model using all known ALL-associated loci in the literature (PseudoR2= 0.166 ± 0.025), which includes loci from GWAS populations that we could not access to train genomic PRS models. Our results suggest that larger and more inclusive GWAS may be needed for genomic PRS to be useful for ALL. Moreover, the comparable performance between populations may suggest a more oligo-genic architecture for ALL, where some large effect loci may be shared between populations. Future PRS models that move away from the infinite causal loci assumption may further improve PRS for ALL.