bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salience network and cognitive impairment in Parkinson’s disease
Authors: Yeager Brooke E , Twedt Hunter P , Bruss Joel , Schultz Jordan , Narayanan Nandakumar S 
Published: October 2023

AbstractParkinson’s disease (PD) is a neurodegenerative disease with cognitive as well as motor impairments. While much is known about the brain networks leading to motor impairments in PD, less is known about the brain networks contributing to cognitive impairments. Here, we leveraged resting-state functional magnetic resonance imaging (rs-fMRI) data from the Parkinson’s Progression Marker Initiative (PPMI) to examine network dysfunction in PD patients with cognitive impairment. We tested the hypothesis that cognitive impairments in PD involve altered connectivity of the salience network (SN), a key cortical network that detects and integrates responses to salient stimuli. We used the Montreal Cognitive Assessment (MoCA) as a continuous index of coarse cognitive function in PD. We report two major results. First, in 82 PD patients we found significant relationships between lower intra-network connectivity of the frontoparietal network (FPN; comprising the dorsolateral prefrontal and posterior parietal cortices bilaterally) with lower MoCA scores. Second, we found significant relationships between lower inter-network connectivity between the SN and the basal ganglia network (BGN) and the default mode network (DMN) with lower MoCA scores. These data support our hypothesis about the SN and provide new insights into the brain networks contributing to cognitive impairments in PD.HighlightsCognitive dysfunction is a prominent clinical symptom in Parkinson’s diseaseFunctional connectivity of the salience network is important for cognitionSalience network dynamics are altered in patients with Parkinson’s diseaseSalience network connectivity with other networks is linked to worse cognition in PD
Harnessing consumer wearable digital biomarkers for individualized recognition of postpartum depression using theAll of UsResearch Program dataset
Authors: Hurwitz Eric , Butzin-Dozier Zachary , Master Hiral , O’Neil Shawn T. , Walden Anita , Holko Michelle , Patel Rena C. , Haendel Melissa A. 
Published: October 2023

AbstractPostpartum depression (PPD), afflicting one in seven women, poses a major challenge in maternal health. Existing approaches to detect PPD heavily depend on in-person postpartum visits, leading to cases of the condition being overlooked and untreated. We explored the potential of consumer wearable-derived digital biomarkers for PPD recognition to address this gap. Our study demonstrated that intra-individual machine learning (ML) models developed using these digital biomarkers can discern between pre-pregnancy, pregnancy, postpartum without depression, and postpartum with depression time periods (i.e., PPD diagnosis). When evaluating variable importance, calories burned from the basal metabolic rate (calories BMR) emerged as the digital biomarker most predictive of PPD. To confirm the specificity of our method, we demonstrated that models developed in women without PPD could not accurately classify the PPD-equivalent phase. Prior depression history did not alter model efficacy for PPD recognition. Furthermore, the individualized models demonstrated superior performance compared to a conventional cohort-based model for the detection of PPD, underscoring the effectiveness of our individualized ML approach. This work establishes consumer wearables as a promising avenue for PPD identification. More importantly, it also emphasizes the utility of individualized ML model methodology, potentially transforming early disease detection strategies.
Spatial and temporal analysis of cholera cases in high-risk areas of Kenya
Authors: Mageto Lydia M , Mutono Nyamai , Aboge Gabriel , Gathura Peter , Okunga Emmanuel , Muange Annastacia , Mbae Cecilia , Thumbi SM , Kariuki Samuel 
Published: October 2023

AbstractCholera outbreaks remain an important public health challenge in Kenya, especially in areas with poor sanitation and hygiene including urban informal settlements, refugee camps and rural areas bordering large water bodies. Even in endemic settings, the distribution of cases exhibits spatial and temporal variations. Utilizing a Poisson discrete space-time scan statistic (SaTScan), this study investigated the temporal trends and the nature of spatial spread of cholera within selected high-risk areas in Kenya. The study was conducted in an urban informal settlement in Nairobi (Mukuru), a refugee camp in Northern Kenya (Dadaab) and the four counties bordering Lake Victoria region. Retrospective cholera line list data from January 2012 to December 2022 in the selected high-risk areas was used. SaTScan v10.1.2 was used to carry out Spatiotemporal analysis and generate spatial clusters. Throughout the study period, a total of 7,372 cholera cases were reported, corresponding to a lower annual incidence rate of 12.2 per 100,000 people compared to a mean annual incidence of 25 cases per 100,000 population previously reported in Kenya. The highest number of cases (n=5934) were reported between 2015 and 2018 with an annual incidence rate of 27.0 per 100,000 people, indicating a relative risk (RR) of 7.22 and a log-likelihood ratio (LLR) of 3015.17 (p< 0.001). The risky clusters (RR>1) were in Dadaab, Fafi, Suna West, Nyatike, Ugunja, Ndhiwa and Suna East sub counties with annual cases of 111.6, 164.1, 28.4, 19.9, 19.4, 14.0 and 13.9 per 100,000, respectively. The sub-counties of Nyakach, Nyando, Rachuonyo East, Kisumu East and Kisumu Central were reported as low-risk clusters, with a relative risk of 0.055 and an annual incidence rate of 1.1 cases per 100,000 individuals. Out of the thirty-two sub-counties included in the study, ten of them did not report any cases of cholera during the study period. Cholera cases waxed every three years in the selected high-risk areas. This data on hotspots specific to endemic settings forms a basis for prompt public health response and resource allocation by prioritizing the significantly high-risk clusters to control and eventually eliminate the disease.
Electrocardiogram sleep staging on par with expert polysomnography
Authors: Jones Adam M. , Itti Laurent , Sheth Bhavin R. 
Published: October 2023

AbstractAccurate classification of sleep stages is crucial in sleep medicine and neuroscience research, providing valuable insights for diagnoses and understanding of brain states. The current gold standard for this task is polysomnography (PSG), an expensive and cumbersome process involving numerous electrodes, often performed in an unfamiliar clinic and professionally annotated. Although commercial devices like smartwatches track sleep, their performance compares poorly with PSG. To address this, we present a neural network that achieves gold-standard levels of agreement using a single lead of electrocardiogram (ECG) data (five-stage Cohen’s kappa = 0.725 on subjects 5 to 90 years old). Our method offers an inexpensive, automated, and convenient alternative. Cardiosomnography, or a sleep study conducted with electrocardiography only, could take expert-level sleep studies outside the confines of clinics and laboratories and into realistic settings. This would render higher-quality studies accessible to a broader community, enabling improved sleep research and sleep-related healthcare interventions.
Polygenic Embryo Screening: High Approval Despite Substantial Concerns from the U.S. Public
Authors: Furrer Rémy A. , Barlevy Dorit , Pereira Stacey , Carmi Shai , Lencz Todd , Lázaro-Muñoz Gabriel 
Published: October 2023

AbstractPolygenic embryo screening (PES) is a novel – yet commercially available – technology that can compute genetic likelihood estimates of polygenic conditions (e.g., diabetes, depression) and traits (e.g., height, cognitive ability) in embryos. Patients undergoing in vitro fertilization (IVF) can use these polygenic scores to select which embryos to transfer for implantation with the goal of having a child. We conducted a survey of the U.S. public to examine attitudes toward PES encompassing acceptance, interest, potential uses, and concerns (n=1435). Our results indicate 72% public approval for PES, with 82% expressing some interest in using PES if already undergoing IVF. Approval for using PES for embryo selection is notably high for physical health (77%) and psychiatric conditions (72%). In contrast, there is minority approval for embryo selection based on PES for behavioral traits (36%) and physical traits (30%). Nevertheless, concerns about PES leading to false expectations, eugenic practices, and stigma are pronounced (54-55% find them “very” to “extremely” concerning). In a second sample of participants (n=192), presenting concerns at survey onset (vs. end) reduced approval (−28%) by mostly increasing ambivalence (+24%), and only slightly increasing disapproval (+4%). Given its commercial availability, practical limitations, and ethical concerns among physicians, patients, geneticists, bioethicists, and legal scholars, it is notable that there is such high public approval and interest in using PES. Understanding these attitudes is essential for informing policymakers, healthcare professionals, and researchers about the public’s perspectives on this novel biotechnology and debate about the role of medicine in regulating the use of PES.
Rurality Modifies the Association Between Symptoms and the Diagnosis of Amyotrophic Lateral Sclerosis
Authors: Hart Alexander A , Swenson Andrea , Narayanan Nandakumar S. , Simmering Jacob E. 
Published: October 2023

AbstractObjectiveWe utilized national claims-based data to identify the change in hazard of diagnosis of ALS following a possible ALS-related diagnosis (e.g., falls) and whether the change in hazard varies whether the patient lives in an urban or rural area.MethodsHealth insurance claims data from both the commercial insurance market and Medicare supplemental market were obtained from the Merative MarketScan Commercial Claims and Encounters and Medicare Coordination of Benefits databases. Individuals with a diagnosis of ALS were identified and matched on age, sex, and enrollment period to individuals without ALS. For all individuals, inciting events such as falls, muscle related symptoms, or bulbar symptoms were also extracted. We then used fixed-effects regression to estimate the risk of being diagnosed with ALS following one of these events controlling for urban-rural status. Additionally, we utilized interaction terms to evaluate the effect of rurality on odds of diagnosis.Results19,126 individuals with ALS were included with 96,126 controls. Patients with ALS were more likely than matched controls to live in an urban area (87 vs 85%). Of those with ALS 84% had a symptom code preceding their diagnosis as compared to 51% in the general population. The association between having any symptoms and future diagnosis of ALS remained statistically significant after adjustment for confounders and an odds ratio of nearly 5. Odds ratios for the individual symptoms varied from 1.2 to over 10. In all models, living in an urban area was associated with increased odds of diagnosis with ALS while the effect of having a symptom was smaller among urban dwellers. Urban dwellers who are diagnosed with ALS are diagnosed at younger ages.ConclusionsEarly diagnosis of ALS is vital for connecting patients with research and treatment options. These results suggest symptoms appear in the administrative health record potentially years before the diagnosis of ALS. Additionally, rural patients are diagnosed at later ages with a greater dependence on major symptoms than urban patients. These results highlight potential improvements for surveillance and screening for ALS.
Safety of hyperbaric oxygen therapy in patients with heart failure: A retrospective review
Authors: Schiavo Simone , Brenna Connor T. A. , Albertini Lisa , Djaiani George , Marinov Anton , Katznelson Rita 
Published: October 2023

AbstractBackgroundHyperbaric oxygen therapy (HBOT) has several hemodynamic effects including increases in afterload (due to vasoconstriction) and decreases in cardiac output. This, along with rare reports of pulmonary edema during emergency treatment, has led providers to consider HBOT relatively contraindicated in patients with reduced left ventricular ejection fraction (LVEF). However, there is limited evidence regarding the safety of elective HBOT in patients with heart failure (HF), and no existing reports of complications among patients with HF and preserved LVEF. We aimed to retrospectively review patients with preexisting diagnoses of HF who underwent elective HBOT, to analyze HBOT-related acute HF complications.MethodsResearch Ethics Board approvals were received to retrospectively review patient charts. Patients with a history of HF with either preserved ejection fraction (HFpEF), mid-range ejection fraction (HFmEF), or reduced ejection fraction (HFrEF) who underwent elective HBOT at two Hyperbaric Centers (Toronto General Hospital, Rouge Valley Hyperbaric Medical Centre) between June 2018 and December 2020 were reviewed.ResultsTwenty-three patients with a history of HF underwent HBOT, completing an average of 39 (range 6 – 62) consecutive sessions at 2.0 atmospheres absolute (ATA) (n=11) or at 2.4 ATA (n=12); only two patients received fewer than 10 sessions. Thirteen patients had HFpEF (mean LVEF 55 ± 7%), and seven patients had HFrEF (mean LVEF 35 ± 8%) as well as concomitantly decreased right ventricle function (n=5), moderate/severe tricuspid regurgitation (n=3), or pulmonary hypertension (n=5). The remaining three patients had HFmEF (mean LVEF 44 ± 4%). All but one patient was receiving fluid balance therapy either with loop diuretics or dialysis. Twenty-one patients completed HBOT without complications. We observed symptoms consistent with HBOT-related HF exacerbation in two patients. One patient with HFrEF (LVEF 24%) developed dyspnea attributed to pulmonary edema after the fourth treatment, and later admitted to voluntarily holding his diuretics before the session. He was managed with increased oral diuretics as an outpatient, and ultimately completed a course of 33 HBOT sessions uneventfully. Another patient with HFpEF (LVEF 64%) developed dyspnea and desaturation after six sessions, requiring hospital admission. Acute coronary ischemia and pulmonary embolism were ruled out, and an elevated BNP and normal LVEF on echocardiogram confirmed a diagnosis of pulmonary edema in the context of HFpEF. Symptoms subsided after diuretic treatment and the patient was discharged home in stable condition, but elected not to resume HBOT.ConclusionsPatients with HF, including HFpEF, may develop HF symptoms during HBOT and warrant ongoing surveillance. However, these patients can receive HBOT safely after optimization of HF therapy and fluid restriction.
A novel reperfusion method in patients with acute ST elevation myocardial infarction during primary percutaneous coronary intervention: A randomized control trial
Authors: He Ji-Fang , Yang Yi-Xing , Liu Yu , Guo Zong-Sheng , Sun Hao , Liang Lu , Jiang Tao , Yang Qi , Lin Xiang-Min , Chen Mu-Lei , Su Pi-Xiong , Yang Xin-Chun , Xu Li , Wang Le-Feng 
Published: October 2023

AbstractBACKGROUNDReperfusion injury is associated with larger infarct size and drawback of long-term outcome in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Volume-Controlled Reperfusion (VCR) is our original reperfusion method combined with accurate gentle reperfusion and active protection for unstable plaque. A single center, prospective, randomized clinical trial was conducted to demonstrate the feasibility, clinical safety, and potential effects of VCR in STEMI patients during PPCI.METHODS AND RESULTSA total of 60 patients with STEMI presenting within 12 h of symptom onset undergoing PPCI were randomized enrolled to VCR group (n=30) or control group (n=30). Patients in VCR group recanalized with VCR followed by routine PCI. Patients in control group recanalized with routine PCI procedure only. The primary endpoint was all-cause death and major adverse cardiac events (MACE) during hospitalization and followed up, the main second endpoints were MVO extent measured 5-7 days post PPCI and left ventricular function. Baseline characteristics were well matched between two groups. No MACE from in-hospital to 1 year followed up in VCR group. In-hospital echocardiography based left ventricular eject fraction (LVEF) in VCR group compared with control group was (57.6 ± 6.2) % vs (52.9 ± 8.5) %, p = 0.018; especially in anterior STEMI VCR subgroup (55.1 ± 6.3) % v (s 48.6 ± 6.4) %, p = 0.003. There was no significant difference in infarct size, MVO mass or MVO mass/infarct mass ratio by late gadolinium enhancement-cardiac magnetic resonance imaging (LGE-CMR). In hospital CMR based LVEF in anterior STEMI VCR subgroup was (50.55 ± 7.55) % vs (40.53 ± 7.39) %, p = 0.002. Follow up echocardiography based LVEF were (64.12 ± 6.35) % vs (59.44 ± 8.20) %, p = 0.025 between two groups and (62.07 ± 7.06) % vs (55.94 ± 6.70) %, p = 0.016 between anterior STEMI subgroups.CONCLUSIONSThis is the pilot RCT study demonstrated that VCR method was feasibility and clinical safe among patients with acute STEMI during PPCI to 12-month follow-up, indicated potential attenuate effect in reperfusion injury as well. Staged II RCT is needed to verify clinical benefit.REGISTRATIONURL:http://www.chictr.org.cn. Unique identifier: ChiCTR00052856
Microbiota-dependent indole production is required for the development of collagen-induced arthritis
Authors: Seymour Brenda J. , Trent Brandon , Allen Brendan , Berlinberg Adam J. , Tangchittsumran Jimmy , Jubair Widian K. , Chriswell Meagan E. , Liu Sucai , Ornelas Alfredo , Stahly Andrew , Alexeev Erica E. , Dowdell Alexander S. , Sneed Sunny L. , Fechtner Sabrina , Kofonow Jennifer M. , Robertson Charles E. , Dillon Stephanie M. , Wilson Cara C. , Anthony Robert M. , Frank Daniel N. , Colgan Sean P. , Kuhn Kristine A. 
Published: October 2023

AbstractAltered tryptophan catabolism has been identified in inflammatory diseases like rheumatoid arthritis (RA) and spondyloarthritis (SpA), but the causal mechanisms linking tryptophan metabolites to disease are unknown. Using the collagen-induced arthritis (CIA) model we identify alterations in tryptophan metabolism, and specifically indole, that correlate with disease. We demonstrate that both bacteria and dietary tryptophan are required for disease, and indole supplementation is sufficient to induce disease in their absence. When mice with CIA on a low-tryptophan diet were supplemented with indole, we observed significant increases in serum IL-6, TNF, and IL-1β; splenic RORγt+CD4+ T cells and ex vivo collagen-stimulated IL-17 production; and a pattern of anti-collagen antibody isotype switching and glycosylation that corresponded with increased complement fixation. IL-23 neutralization reduced disease severity in indole-induced CIA. Finally, exposure of human colon lymphocytes to indole increased expression of genes involved in IL-17 signaling and plasma cell activation. Altogether, we propose a mechanism by which intestinal dysbiosis during inflammatory arthritis results in altered tryptophan catabolism, leading to indole stimulation of arthritis development. Blockade of indole generation may present a novel therapeutic pathway for RA and SpA.
Using the pan-genomic framework for the discovery of genomic islands in the haloarchaeonHalorubrum ezzemoulense
Authors: Feng Yutian , Arsenault Danielle , Louyakis Artemis S. , Altman-Price Neta , Gophna Uri , Papke R. Thane , Gogarten Johann Peter 
Published: October 2023

AbstractIn this study, we use pan-genomics to characterize the organized variability from the widely dispersed halophilic archaeal speciesHalorubrum ezzemoulense. We include a multi-regional sampling of newly sequenced, high-quality draft genomes. Using the pan-genome graph of the species, we discover 50 genomic islands which represent rare accessory genetic capabilities available to members of the species. 19 of these islands are likely the remnant of mobile genetic elements and are enriched for genomic dark matter. 10 islands encode for niche adapting solute transporters, with a cosmopolitan but limited distribution throughout the strains. We also observe rearrangements which have led to the insertion/recombination/replacement of mutually exclusive genomic islands in equivalent genome positions (“homeocassettes”). These conflicting islands encode for similar functions, but homologs from islands located between the same core genes exhibit extreme divergence on the amino acid level. Homeocasettes provide variations for a homologous function, which may confer a greater range of adaptability to the species group. We observe some islands that appear geographically restricted; however, we also observe the coexistence of genomes, in a single geographic region, with and without certain genomic islands, demonstrating the retention and spread of rare genes in the pan-genome.ImportanceUnderstanding the evolution of genome content is a key puzzle in evolutionary biology. Despite its importance, this area hasn’t received thorough investigation. This is especially true of Archaeal organisms, which constitute a large fraction of Earth’s diversity, but are often referred to as the “forgotten” or “third” domain of life. This study dives into those questions by finding rare genes amongst a group of closely related Archaeal species, and describes how their transfer, utilization and persistence may contribute to the speciation and specialization of the group.
High confidence glycosomal membrane protein inventory unveils trypanosomal Peroxin PEX15
Authors: Krishna Chethan K. , Das Hirak , Hohnen Lisa , Schliebs Wolfgang , Oeljeklaus Silke , Warscheid Bettina , Kalel Vishal C. , Erdmann Ralf 
Published: October 2023

AbstractInfections by trypanosomatid parasites cause Chagas disease, Human African Trypanosomiasis, and Leishmaniasis, affecting over 12 million people worldwide. Glycosomes, the unique peroxisome-related organelles of trypanosomes are essential for their survival, and hence their metabolic functions and biogenesis mediated by peroxins (PEX) are suitable as drug targets. Here we report on a comprehensive protein inventory of glycosomal membranes through advanced subcellular membrane protein profiling employing quantitative mass spectrometry. Our quantitative analysis resulted in the identification of 28 novel high confidence glycosomal membrane proteins. Our in-depth protein inventory of glycosomal membranes serves as an important resource for characterizing glycosome biology and drug development. We validated four so far unknown glycosomal membrane proteins, including two tail-anchored (TA) proteins, a homolog of human peroxisomal PXMP4, and a Macrodomain-containing protein. Using a structure-based approach, we identified one of the TA proteins as the long-soughtTrypanosomaPEX15. Despite its low sequence similarity,TrypanosomaPEX15 exhibits structural and topological similarities with its yeast (Pex15) and human counterparts (PEX26). We show that PEX15 is an essential integral glycosomal membrane protein that interacts with PEX6. Accordingly, RNAi knockdown of PEX15 in bloodstream form trypanosomes demonstrates that it is essential for glycosome biogenesis and parasite survival. Considering the low degree of conservation with its human counterpart, PEX15 is a promising molecular target for drug development.