bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sevoflurane-based enhancement of phase-amplitude coupling and localization of the epileptogenic zone
Authors: Wada Keiko , Sonoda Masaki , Firestone Ethan , Sakakura Kazuki , Kuroda Naoto , Takayama Yutaro , Iijima Keiya , Iwasaki Masaki , Mihara Takahiro , Goto Takahisa , Asano Eishi , Miyazaki. Tomoyuki 
Published: October 2021

ABSTRACTObjectivePhase-amplitude coupling between high-frequency (≥150 Hz) and delta (3-4 Hz) oscillations - modulation index (MI) - is a promising, objective biomarker of epileptogenicity. We determined whether sevoflurane anesthesia preferentially enhances this metric within the epileptogenic zone.MethodsThis is an observational study of intraoperative electrocorticography data from 621 electrodes chronically implanted into eight patients with drug-resistant, focal epilepsy. All patients were anesthetized with sevoflurane during resective surgery, which subsequently resulted in seizure control. We classified ‘removed’ and ‘retained’ brain sites as epileptogenic and non-epileptogenic, respectively. Mixed model analysis determined which anesthetic stage optimized MI-based classification of epileptogenic sites.ResultsMI increased as a function of anesthetic stage, ranging from baseline (i.e., oxygen alone) to 2 minimum alveolar concentration (MAC) of sevoflurane, preferentially at sites showing higher initial MI values. This phenomenon was accentuated just prior to sevoflurane reaching 2 MAC, at which time, the odds of a site being classified as epileptogenic were enhanced by 86.6 times for every increase of 1 MI.ConclusionsIntraoperative MI best localized the epileptogenic zone immediately before sevoflurane reaching 2 MAC in this small cohort of patients.SignificanceProspective, large cohort studies are warranted to determine whether sevoflurane anesthesia can reduce the need for extraoperative, invasive evaluation.Highlights-We measured the modulation index on intraoperative electrocorticography recording.-Sevoflurane enhanced the modulation index differentially across the epileptogenic and non- epileptogenic sites.-The modulation index best discriminated these two groups of sites before sevoflurane reached 2 minimum alveolar concentration.
Linking common and rare disease genetics through gene regulatory networks
Authors: Bakker Olivier B. , Claringbould Annique , Westra Harm-Jan , Wiersma Henry , Boulogne Floranne , Võsa Urmo , Symmons Sophie Mulcahy , Jonkers Iris H. , Franke Lude , Deelen Patrick 
Published: October 2021

AbstractGenetic variants identified through genome-wide association studies (GWAS) are typically non-coding and exert small regulatory effects on downstream genes, but which downstream genes are ultimately impacted and how they confer risk remains mostly unclear. Conversely, variants that cause rare Mendelian diseases are often coding and have a more direct impact on disease development. We demonstrate that common and rare genetic diseases can be linked by studying the gene regulatory networks impacted by common disease-associated variants. We implemented this in the ‘Downstreamer’ method and applied it to 44 GWAS traits and find that predicted downstream “key genes” are enriched with Mendelian disease genes, e.g. key genes for height are enriched for genes that cause skeletal abnormalities and Ehlers-Danlos syndromes. We find that 82% of these key genes are located outside of GWAS loci, suggesting that they result from complex trans regulation rather than being impacted by disease-associated variants in cis. Finally, we discuss the challenges in reconstructing gene regulatory networks and provide a roadmap to improve identification of these highly connected genes for common traits and diseases.
Associations between sustainable development goals accelerators and well-being, by household heads’ disability status among adolescents in Zambia – a cross-sectional study
Authors: Chipanta David , Estill Janne , Stöckl Heidi , Hertzog Lucas , Toska Elona , Chanda Patrick , Mwanza Jason , Kaila Kelly , Matome Chisangu , Tembo Gelson , Keiser Olivia , Cluver Lucie 
Published: October 2021

AbstractObjectivesWe examined associations between accelerators (interventions impacting two or more SDG targets) and well-being indicators among adolescents in Zambia.MethodsWe randomly sampled 1,800 households receiving social cash transfers (SCT) in four districts, surveyed adults 16 years and older. Using multivariable logistic regressions, stratified by household heads disability status, we examined associations between accelerators (SCT, life-long learning (LLL), mobile phone access (MPA)) and seven well-being indicators among adolescents 16 to 24 years old. We predicted adolescents’ probabilities of reporting indicators using marginal effects models.ResultsWe included 1,725 adolescents, 881(51.1%) girls. MPA was associated with no poverty (adjusted Odds Ratio [aOR] 2.08, p<0.001), informal cash transfers (aOR 1.82 p=0.004), seeking mental support (aOR 1.61, p=0.020); SCT with no health access restrictions related to disability (aOR 2.56, p=0.004), lesser odds seeking mental support (aOR 0.53, p=0.029); LLL with informal cash transfers (aOR 3.49, p<0.001), lower school enrolment (aOR 0.70, p=0.004). Adolescents living with disabled household heads reported worse poverty, good health, less suicidal ideation.ConclusionsAccelerators - SCT, LLL, MPA - were associated with well-being indicators. Adolescents living with disabled household heads benefited less.Relevance to SDGsThis paper shows that adopting accelerators can help achieve SDGs-aligned well-being indicators for adolescents living in poverty. However, accelerators may not offset disability-related inequalities. Adolescents living with disabled household heads may require more attention to achieve the SDGs.SDGs targets1.2. no poverty; 1.3.1 social cash transfers, Informal cash transfers; 3. good Health; 3.4. no suicidal ideation; 3.4. seeking mental support; 4.1. school enrolment; 10. no health access restrictions related to disability.
Clinical performance characteristics of the Swift Normalase Amplicon Panel for sensitive recovery of SARS-CoV-2 genomes
Authors: Shrestha Lasata , Lin Michelle J. , Xie Hong , Mills Margaret G. , Bakhash Shah A. Mohamed , Gaur Vinod P. , Livingston Robert J. , Castor Jared , Bruce Emily A. , Botten Jason W. , Huang Meei-Li , Jerome Keith R. , Greninger Alexander L. , Roychoudhury Pavitra 
Published: October 2021

ABSTRACTAmplicon-based sequencing methods have been central in characterizing the diversity, transmission and evolution of SARS-CoV-2, but need to be rigorously assessed for clinical utility. Here, we validated the Swift Biosciences’ SARS-CoV-2 Swift Normalase Amplicon Panels using remnant clinical specimens. High quality genomes meeting our established library and sequence quality criteria were recovered from positive specimens with a 95% limit of detection of ≥ 40.08 SARS-CoV-2 copies/PCR reaction. Breadth of genome recovery was evaluated across a range of Ct values (11.3 – 36.7, median 21.6). Out of 428 positive samples, 406 (94.9%) generated genomes with < 10% Ns, with a mean genome coverage of 13,545X ± SD 8,382X. No genomes were recovered from PCR-negative specimens (n = 30), or from specimens positive for non-SARS-CoV-2 respiratory viruses (n = 20). Compared to whole-genome shotgun metagenomic sequencing (n = 14) or Sanger sequencing for the spike gene (n = 11), pairwise identity between consensus sequences was 100% in all cases, with highly concordant allele frequencies (R2= 0.99) between Swift and shotgun libraries. When samples from different clades were mixed at varying ratios, expected variants were detected even in 1:99 mixtures. When deployed as a clinical test, 268 tests were performed in the first 23 weeks with a median turnaround time of 11 days, ordered primarily for outbreak investigations and infection control.
qMRI-BIDS: an extension to the brain imaging data structure for quantitative magnetic resonance imaging data
Authors: Karakuzu Agah , Appelhoff Stefan , Auer Tibor , Boudreau Mathieu , Feingold Franklin , Khan Ali R. , Lazari Alberto , Markiewicz Christopher J. , Mulder Martijn J. , Phillips Christophe , Salo Taylor , Stikov Nikola , Whitaker Kirstie , de Hollander Gilles 
Published: October 2021

AbstractThe Brain Imaging Data Structure (BIDS) established community consensus on the organization of data and metadata for several neuroimaging modalities. Traditionally, BIDS had a strong focus on functional magnetic resonance imaging (MRI) datasets and lacked guidance on how to store multimodal structural MRI datasets. Here, we present and describe the BIDS Extension Proposal 001 (BEP001), which adds a range of quantitative MRI (qMRI) applications to the BIDS application sphere. In general, the aim of qMRI is to characterize brain microstructure by quantifying the physical MR parameters of the tissue via computational, biophysical models. By proposing this new standard, we envision standardization of qMRI which makes multicenter dissemination of interoperable data possible. As a result, BIDS can act as a catalyst of convergence between qMRI methods development and application-driven neuroimaging studies that can help develop quantitative biomarkers for neural tissue characterization. Finally, our BIDS extension offers a common ground for developers to exchange novel imaging data and tools, reducing the practical barriers to standardization that is currently lacking in the field of neuroimaging.
SPARClink: an interactive tool to visualize the impact of the SPARC program
Authors: Soundarajan Sanjay , Kuruppu Sachira , Singh Ashutosh , Kim Jongchan , Achalla Monalisa 
Published: October 2021

AbstractThe NIH SPARC program seeks to accelerate the development of therapeutic devices that modulate electrical activity in nerves to improve organ function. SPARC-funded researchers are generating rich datasets from neuromodulation research that are curated and shared according to FAIR (Findable, Accessible, Interoperable, and Reusable) guidelines and are accessible to the public on the SPARC data portal. Keeping track of the utilization of these datasets within the larger research community is a feature that will benefit data generating researchers in showcasing the impact of their SPARC outcomes. This will also allow the SPARC program to display the impact of the FAIR data curation and sharing practices that have been implemented. This manuscript provides the methods and outcomes of SPARClink, our web tool for visualizing the impact of SPARC, which won the 2nd prize at the 2021 SPARC FAIR Codeathon. With SPARClink, we built a system that automatically and continuously finds new published SPARC scientific outputs (datasets, publications, protocols) and the external resources referring to them. SPARC datasets and protocols are queried using publicly accessible REST APIs (provided by Pennsieve and Protocols.io) and stored in a publicly accessible database. Citation information for these resources is retrieved using the NIH reporter API and NCBI Entrez system. A novel knowledge-graph-based structure was created to visualize the results of these queries and showcase the impact that the FAIR data principles can have on the research landscape when they are adopted by a consortium.
Sex Modifies the Effect of Genetic Risk Scores for Polycystic Ovary Syndrome on Metabolic Phenotypes
Authors: Actkins Ky’Era V. , Jean-Pierre Genevieve , Aldrich Melinda C. , Velez Edwards Digna R. , Davis Lea K. 
Published: October 2021

AbstractFemales with polycystic ovary syndrome (PCOS), the most common endocrine disorder in women, have an increased risk of developing metabolic disorders such as insulin resistance, obesity, and type 2 diabetes (T2D). Furthermore, while only diagnosable in females, males with a family history of PCOS can also exhibit a poor cardiometabolic profile. Therefore, we aimed to elucidate the role of sex in the relationship between PCOS and its comorbidities by conducting bidirectional genetic risk score analyses in both sexes. We conducted a phenome-wide association study (PheWAS) using PCOS polygenic risk scores (PCOSPRS) to understand the pleiotropic effects of PCOS genetic liability across 1,380 medical conditions in females and males recorded in the Vanderbilt University Medical Center electronic health record (EHR) database. After adjusting for age and genetic ancestry, we found that European descent males with higher PCOSPRS were significantly more likely to develop cardiovascular diseases than females at the same level of genetic risk, while females had a higher odds of developing T2D. Based on observed significant associations, we tested the relationship between PRS for comorbid conditions (e.g., T2D, body mass index, hypertension, etc.) and found that only PRS generated for BMI and T2D were associated with a PCOS diagnosis. We then further decomposed the T2DPRS association with PCOS by adjusting the model for measured BMI and BMIresidual (enriched for the environmental contribution to BMI). Results demonstrated that genetically regulated BMI primarily accounted for the relationship between T2DPRS and PCOS. This was further supported in a mediation analysis, which only revealed clinical BMI measurements, but not BMIresidual, as a strong mediator for both sexes. Overall, our findings show that the genetic architecture of PCOS has distinct metabolic sex differences, but these associations are only apparent when PCOSPRS is explicitly modeled. It is possible that these pathways are less explained by the direct genetic risk of metabolic traits than they are by the risk factors shared between them, which can be influenced by biological variables such as sex.
The 1968 Influenza Pandemic and COVID-19 Outcomes
Authors: Taylor Charles A , Boulos Christopher , Memoli Matthew J. 
Published: October 2021

AbstractPast pandemic experience can affect health outcomes in future pandemics. This paper focuses on the last major influenza pandemic in 1968 (H3N2), which killed up to 100,000 people in the US. We find that places with high influenza mortality in 1968 experienced 1-4% lower COVID-19 death rates. Our identification strategy isolates variation in COVID-19 rates across people born before and after 1968. In places with high 1968 influenza incidence, older cohorts experience lower COVID-19 death rates relative to younger ones. The relationship holds using county and patient-level data, as well as in hospital and nursing home settings. Results do not appear to be driven by systemic or policy-related factors, instead suggesting an individual-level response to prior influenza pandemic exposure. The findings merit investigation into potential biological and immunological mechanisms that account for these differences—and their implications for future pandemic preparedness.
Safety and Efficacy of Daclatasvir with Sofosbuvir and Ribavirin in Hepatitis C Virus Infection: A Real World Experience from South Punjab, Pakistan
Authors: Malghani Waseem Sarwar , Din Chaudhary Farooq Mohyud , Shahid Misbah , Tameez-ud-din Ahsan , Malik Romaisa , Tameez Ud Din Asma 
Published: October 2021

AbstractBackground & ObjectivesSofosbuvir (SOF) and daclatasvir (DCV) in combination with ribavirin (RBV) drastically changed the treatment scenario of chronic hepatitis C (CHC) patients, achieving remarkable efficacy and safety profile. Real world experience of SOF/DCV/RBV combination in this part of Asia was scant. This study aimed to evaluate the efficacy and safety of SOF/DCV/RBV combination to treat CHC patients at a tertiary care hospital in South Punjab.MethodsPatients of CHC of any genotype were enrolled prospectively. They were treated with 12 weeks course of SOF/DCV/RBV combination. Effectiveness was evaluated by end of treatment response (ETR) and sustained virological response (SVR) at 12 and 24 weeks post-treatment. Adverse events were recorded for safety analysis.ResultsWe analyzed data of 102 patients of CHC (40 males and 62 females). The mean age was 40.04 + 10.22 years. Mean weight was 67.24 + 11.78 kg, while mean body mass index (BMI) was 26.32 + 4.58 kg/m2. Eighty patients belonged to low socio-economic status, while 22 belonged to middle socio-economic status. Sixty-four had a rural background, while 38 were from urban background. Seventy-four patients had no co-morbid condition; 16 (15.7%) had diabetes and 12 (11.8%) patients had co-morbid hypertension. Ninety percent of the patients did not have cirrhosis; 6% had compensated liver disease, while 4 % had decompensated liver disease. All the patients achieved undetectable HCV RNA at the end of treatment and 12 weeks after completion of treatment, while SVR at 24 weeks was achieved in 98% of patients. Only 2 patients discontinued treatment as a result of side effects. The most common side effects reported include fatigue, headache and fever.ConclusionCHC is a grave problem in developing countries like Pakistan. The SOF/DCV/RBV combination is very effective in eradicating CHC and has a very good side effect profile as well.
MRI based Kidney Radiomics analysis during chronic lithium treatment: validation of a texture index associated with decreased kidney function
Authors: Beunon Paul , Barat Maxime , Dohan Anthony , Cheddani Lynda , Males Lisa , Fernandez Pedro , Etain Bruno , Bellivier Frank , Vrtovsnik François , Vidal-Petiot Emmanuelle , Khalil Antoine , Flamant Martin , Tabibzadeh Nahid 
Published: October 2021

AbstractBackgroundChronic lithium therapy is associated with an increased risk of chronic kidney disease (CKD). Lithium nephrotoxicity is slowly progressive and difficult to detect at early stages. The aim of this study was to identify specific image texture changes of kidneys as possible imaging biomarkers of decreased measured glomerular filtration rate (mGFR) using radiomic analysis of T2 weighted imaging magnetic resonance imaging.MethodsOne hundred and nine patients treated with lithium carbonate were evaluated including mGFR and Kidney MRI, with T2 weighted sequence single-shot fast spin-echo. Computed radiomic analysis was performed after a manual kidney segmentation. Significant features were selected to build a radiomic signature using multivariable Cox analysis to detect a decreased mGFR <60 ml/min/1.73m2. The texture index was internally validated using a training and a validation cohort.ResultsTexture analysis index was able to detect a decrease in mGFR, with an Area Under the Curve (AUC) of 0.85 in the training cohort and 0.71 in the validation cohort. Patients with a texture index below the median were older (59 [42-66] versus 46 [34-54] years, p=0.001), with longer treatment duration (10 [3-22] versus 6 [2-10] years, p=0.02), and a lower mGFR (66 [46-84] versus 83 [71-94] ml/min/1.73m2, p<0.001). Texture analysis index was independently and negatively associated with age (β= -0.004 ±0.001, p<0.001), serum vasopressin (−0.005 ± 0.002, p=0.02), lithium treatment duration (−0.01 ± 0.003, p=0.001), with a significant interaction between lithium treatment duration and mGFR (p=0.02).ConclusionA renal texture index was developed and validated among patients treated with lithium carbonate associated with a decreased mGFR. This index might be relevant in the diagnosis and prognosis of lithium-induced renal toxicity.
Double-check the zebrafish18s rRNAqPCR primers: they may be wrong
Authors: Wang Jianing , Yang Zhipeng , Xiao An 
Published: October 2021

AbstractA widely used qPCR primer for zebrafish generna18s(18s rRNA, or18s), with the sequence of 5’-TCGCtaGTtGGCATCGTTTAtG-3’, is found to be incorrect. Initially designed for rainbow trout (Oncorhynchus mykiss)rna18s, the primer has four different nucleotides from the zebrafish sequence 5’-TCGCGGGTCGGCATCGTTTACG-3’ (indicated in bold/underlined, lowercase letters for rainbow trout and uppercase letters for zebrafish). Since its first use in zebrafish in 2006, this mismatched primer has been clearly stated to be used in at least 50 publications and may have affected hundreds or more in publications citing them. For a sensitive, quantitative method as qPCR, this error must be corrected as soon as possible in the zebrafish community by usingrna18sprimer sets with accurate sequences, such as those summarized and newly designed in this article.
Patient-specific analysis of bicuspid aortic valve hemodynamics using a fully coupled fluid-structure interaction (FSI) model
Authors: Qin Tongran , Caballero Andrés , Mao Wenbin , Barrett Brian , Kamioka Norihiko , Lerakis Stamatios , Sun Wei 
Published: October 2021

ABSTRACTBicuspid aortic valve (BAV), the most common congenital heart disease, is prone to develop significant valvular dysfunction and aortic wall abnormalities. Growing evidence has suggested that abnormal BAV hemodynamics could contribute to the disease progression. In order to investigate the BAV hemodynamic, we performed 3D patient-specific fluid-structure interaction (FSI) simulations of BAV with fully coupled flow dynamics and valve motions throughout the cardiac cycle. The results showed that the flow during systole can be characterized by a systolic jet and two counter-rotating recirculation vortices. At peak systole, the jet was usually eccentric, with asymmetric recirculation vortices, and helical flow motion in the ascending aorta. The flow structure at peak systole was quantified using the vorticity, flow reversal ratio and helicity index at four locations from the aortic root to the ascending aorta. The systolic jet was evaluated using the metrics including the peak velocity, normalized flow displacement, and jet angle. It was found that both the peak velocity and normalized flow displacement (rather than jet angle) of the systolic jet showed a strong correlation with the vorticity and helicity index of the flow in the ascending aorta, which suggests that these two metrics can be used for noninvasive evaluation of abnormal flow patterns in BAV patients.
Impact of biologics and small molecules for Inflammatory Bowel Disease on COVID-19 Related Hospitalization: A Systematic Review and Meta-analysis
Authors: Alrashed Fatema , Alasfour Hajer , Shehab Mohammad 
Published: October 2021

AbstractBackgroundThe use of biological therapies and small molecules have been a concern for patients with inflammatory bowel disease (IBD) during COVID-19 pandemic. We aim to assess the association between risk of COVID-19 related hospitalization and these agents.MethodA systematic review and meta-analysis of all published studies from December 2019 to September 2021 was performed to identify studies that reported COVID-19 related hospitalization in IBD patients receiving biological therapies or tofacitinib. The risk ratio (RR) was calculated to compare the relative risk of COVID-19 related hospitalization in patients receiving these medications to those who were not, at the time of the study.Results18 studies were included. The relative risk of hospitalization was significantly lower in patients with IBD and COVID-19 who were receiving biologic therapy with RR of 0.47 (95% CI: 0.42-0.52, p < 0.00001). The RR was lower in patients receiving anti-TNFs compared to those who did not [RR= 0.48 (95% CI: 0.41-0.55, p < 0.00001)]. Similar finding was observed in patients taking ustekinumab [RR= 0.55 (95% CI: 0.43-0.72, p < 0.00001)]. Combination therapy of anti-TNF and an immunomodulator did not lower the risk of COVID-19 related hospitalization [RR= 0.98 (95% CI: 0.82-1.18, p =0.84]. The use of vedolizumab [RR= 1.13 (95% CI: 0.75-1.73, p =0.56] and tofacitinib [RR= 0.81 (95% CI: 0.49-1.33, p =0.40] was not associated with lower risk of COVID-19 related hospitalization.ConclusionRegarding COVID-19 related hospitalization in IBD, anti-TNFs and ustekinumab were associated with favorable outcomes. In addition, vedolizumab and tofacitinib were not associated with COVID-19 related hospitalization.