bluuebunny/crossref_metadata_2025_split huggingface dataset:
Giant axonal neuropathy: cross-sectional analysis of a large natural history cohort
Authors: Bharucha-Goebel Diana X , Norato Gina , Saade Dimah , Paredes Eduardo , Biancavilla Victoria , Donkervoort Sandra , Kaur Rupleen , Lehky Tanya , Fink Margaret , Armao Diane , Gray Steven J , Waite Melissa , Debs Sarah , Averion Gilberto , Hu Ying , Zein Wadih M , Foley A Reghan , Jain Minal , Bönnemann Carsten G 
Published: June 2021

AbstractGiant axonal neuropathy (GAN) is an ultra-rare autosomal recessive, progressive neurodegenerative disease with early childhood onset that presents as a prominent sensorimotor neuropathy and commonly progresses to affect both the PNS and CNS. The disease is caused by biallelic mutations in the GAN gene located on 16q23.2, leading to loss of functional gigaxonin, a substrate specific ubiquitin ligase adapter protein necessary for the regulation of intermediate filament turnover.Here, we report on cross-sectional data from the first study visit of a prospectively collected natural history study of 45 individuals, age range 3–21 years with genetically confirmed GAN to describe and cross-correlate baseline clinical and functional cohort characteristics.We review causative variants distributed throughout the GAN gene in this cohort and identify a recurrent founder mutation in individuals with GAN of Mexican descent as well as cases of recurrent uniparental isodisomy. Through cross-correlational analysis of measures of strength, motor function and electrophysiological markers of disease severity, we identified the Motor Function Measure 32 to have the strongest correlation across measures and age in individuals with GAN. We analysed the Motor Function Measure 32 scores as they correspond to age and ambulatory status. Importantly, we identified and characterized a subcohort of individuals with a milder form of GAN and with a presentation similar to Charcot–Marie–Tooth disease. Such a clinical presentation is distinct from the classic presentation of GAN, and we demonstrate how the two groups diverge in performance on the Motor Function Measure 32 and other functional motor scales. We further present data on the first systematic clinical analysis of autonomic impairment in GAN as performed on a subset of the natural history cohort.Our cohort of individuals with genetically confirmed GAN is the largest reported to date and highlights the clinical heterogeneity and the unique phenotypic and functional characteristics of GAN in relation to disease state. The present work is designed to serve as a foundation for a prospective natural history study and functions in concert with the ongoing gene therapy trial for children with GAN.
Context Sensitivity across Multiple Time scales with a Flexible Frequency Bandwidth
Authors: Regev Tamar I , Markusfeld Geffen , Deouell Leon Y , Nelken Israel 
Published: June 2021

Abstract
Everyday auditory streams are complex, including spectro-temporal content that varies at multiple timescales. Using EEG, we investigated the sensitivity of human auditory cortex to the content of past stimulation in unattended sequences of equiprobable tones. In 3 experiments including 82 participants overall, we found that neural responses measured at different latencies after stimulus onset were sensitive to frequency intervals computed over distinct timescales. Importantly, early responses were sensitive to a longer history of stimulation than later responses. To account for these results, we tested a model consisting of neural populations with frequency-specific but broad tuning that undergo adaptation with exponential recovery. We found that the coexistence of neural populations with distinct recovery rates can explain our results. Furthermore, the adaptation bandwidth of these populations depended on spectral context—it was wider when the stimulation sequence had a wider frequency range. Our results provide electrophysiological evidence as well as a possible mechanistic explanation for dynamic and multiscale context-dependent auditory processing in the human cortex.
Time to Viral Rebound After Interruption of Modern Antiretroviral Therapies
Authors: Li Jonathan Z , Aga Evgenia , Bosch Ronald J , Pilkinton Mark , Kroon Eugène , MacLaren Lynsay , Keefer Michael , Fox Lawrence , Barr Liz , Acosta Edward , Ananworanich Jintanat , Coombs Robert , Mellors John W , Landay Alan L , Macatangay Bernard , Deeks Steven , Gandhi Rajesh T , Smith Davey M 
Published: June 2021

AbstractBackgroundDevelopment of human immunodeficiency virus (HIV) remission strategies requires precise information on time to HIV rebound after treatment interruption, but there is uncertainty regarding whether modern antiretroviral therapy (ART) regimens and timing of ART initiation may affect this outcome.MethodsAIDS Clinical Trials Group (ACTG) A5345 enrolled individuals who initiated ART during chronic or early HIV infection and on suppressive ART for ≥2 years. Participants underwent carefully monitored antiretroviral interruption. ART was restarted upon 2 successive viral loads ≥1000 copies/mL. We compared participants of A5345 with participants of 6 historic ACTG treatment interruption studies.ResultsThirty-three chronic-treated and 12 early-treated participants interrupted ART with evaluable time to viral rebound. Median time to viral rebound ≥1000 HIV RNA copies/mL was 22 days. Acute retroviral rebound syndrome was diagnosed in 9% of the chronic-treated and none of the early-treated individuals. All participants of the historic studies were on older protease inhibitor-based regimens, whereas 97% of A5345 participants were on integrase inhibitor-based ART. There were no differences in the timing of viral rebound comparing A5345 versus historic studies. In a combined analysis, a higher percentage of early-treated participants remained off ART at posttreatment interruption week 12 (chronic vs early: 2% vs 9%, P = .0496). One chronic-treated and one early-treated A5345 participant remained off ART for &gt;24 weeks. All participants resuppressed after ART reinitiation.ConclusionsEarly ART initiation, using either older or newer ART regimens, was associated with a significant delay in the time to HIV rebound after ART interruption, lowering the barrier for HIV remission.
Impact of chronic kidney disease on the pharmacodynamic and pharmacokinetic effects of ticagrelor in patients with diabetes mellitus and coronary artery disease
Authors: Franchi Francesco , Rollini Fabiana , Been Latonya , Maaliki Naji , Abou Jaoude Patrick , Rivas Andrea , Zhou Xuan , Jia Sida , Briceno Maryuri , Lee Chang Hoon , Pineda Andres M , Suryadevara Siva , Soffer Daniel , Zenni Martin M , Bass Theodore A , Angiolillo Dominick J 
Published: June 2021

Abstract

Aims
Patients with diabetes mellitus (DM) and chronic kidney disease (CKD) are at increased risk of atherothrombotic events. Ticagrelor reduces ischaemic events compared to clopidogrel, with the greatest risk reduction in patients with both DM and CKD. How CKD status affects the pharmacodynamic (PD) and pharmacokinetic (PK) profiles of different ticagrelor maintenance dose regimens in patients with DM is unknown.

Methods and results
In this randomized, crossover study, patients with DM on treatment with dual antiplatelet therapy (aspirin and clopidogrel) were stratified according to CKD status and randomized to ticagrelor 90 or 60 mg bid. PK/PD assessments were performed at baseline, after 7–10 days of ticagrelor (peak and trough), and after 7–10 days of alternative ticagrelor regimen (peak and trough). PK assessments included plasma concentrations of ticagrelor and its major metabolite. PD assessments included vasodilator-stimulated phosphoprotein (VASP)–platelet reactivity index (PRI), VerifyNow P2Y12, and light transmittance aggregometry (LTA). A total of 92 patients with DM (CKD, n = 44; non-CKD, n = 48) were randomized. Levels of platelet reactivity were lower with the 90 mg compared with the 60 mg ticagrelor dose, which was statistically significant in non-CKD but not in CKD patients for most PD measures. There were no significant differences in the primary endpoint (trough levels of VASP–PRI following ticagrelor 90 mg dosing) between cohorts (31 ± 20 vs. 25 ± 14; P = 0.105). VerifyNow and LTA provided similar findings. PK assessments tracked PD profiles showing increased plasma concentrations of ticagrelor and its major metabolite in CKD compared to non-CKD patients.

Conclusion
In patients with DM, although ticagrelor maintenance dose regimens (60 and 90 mg) yield potent P2Y12 inhibition, levels of platelet reactivity tended to be higher and subject to broader variability in non-CKD compared with CKD patients.

Clinical trial registration
http://www.clinicaltrials.gov Unique Identifier: NCT02539160.
Did giraffe cardiovascular evolution solve the problem of heart failure with preserved ejection fraction?
Authors: Natterson-Horowitz Barbara , Baccouche Basil M , Head Jennifer Mary , Shivkumar Tejas , Bertelsen Mads Frost , Aalkjær Christian , Smerup Morten H , Ajijola Olujimi A , Hadaya Joseph , Wang Tobias 
Published: June 2021

Abstract
The evolved adaptations of other species can be a source of insight for novel biomedical innovation. Limitations of traditional animal models for the study of some pathologies are fueling efforts to find new approaches to biomedical investigation. One emerging approach recognizes the evolved adaptations in other species as possible solutions to human pathology. The giraffe heart, for example, appears resistant to pathology related to heart failure with preserved ejection fraction (HFpEF)—a leading form of hypertension-associated cardiovascular disease in humans. Here, we postulate that the physiological pressure-induced left ventricular thickening in giraffes does not result in the pathological cardiovascular changes observed in humans with hypertension. The mechanisms underlying this cardiovascular adaptation to high blood pressure in the giraffe may be a bioinspired roadmap for preventive and therapeutic strategies for human HFpEF.
Matching Methods for Confounder Adjustment: An Addition to the Epidemiologist’s Toolbox
Authors: Greifer Noah , Stuart Elizabeth A 
Published: June 2021

AbstractPropensity score weighting and outcome regression are popular ways to adjust for observed confounders in epidemiologic research. Here, we provide an introduction to matching methods, which serve the same purpose but can offer advantages in robustness and performance. A key difference between matching and weighting methods is that matching methods do not directly rely on the propensity score and so are less sensitive to its misspecification or to the presence of extreme values. Matching methods offer many options for customization, which allow a researcher to incorporate substantive knowledge and carefully manage bias/variance trade-offs in estimating the effects of nonrandomized exposures. We review these options and their implications, provide guidance for their use, and compare matching methods with weighting methods. Because of their potential advantages over other methods, matching methods should have their place in an epidemiologist’s methodological toolbox.
COVID-19 mRNA Vaccination Generates Greater Immunoglobulin G Levels in Women Compared to Men
Authors: Demonbreun Alexis R , Sancilio Amelia , Velez Matt E , Ryan Daniel T , Pesce Lorenzo , Saber Rana , Vaught Lauren A , Reiser Nina L , Hsieh Ryan R , D’Aquila Richard T , Mustanski Brian , McDade Thomas W , McNally Elizabeth M 
Published: June 2021

Abstract
We investigated whether the antibody response to coronavirus disease 2019 (COVID-19) mRNA vaccination is similar in women and men. In a community cohort without prior COVID-19, first vaccine dose produced higher immunoglobulin G (IgG) levels and percent inhibition of spike-ACE2 receptor binding, a surrogate measure of virus neutralization, in women compared to men (7.0 µg/mL, 51.6% vs 3.3 µg/mL, 36.4%). After 2 doses, IgG levels remained significantly higher for women (30.4 µg/mL) compared to men (20.6 µg/mL), while percent inhibition was similar (98.4% vs 97.7%). Sex-specific antibody response to mRNA vaccination informs future efforts to understand vaccine protection and side effects.
Toxicological Relevance of Pregabalin in Heroin Users: A Two-Year Postmortem Population Study
Authors: Nahar Limon K , Murphy Kevin , Paterson Sue 
Published: June 2021

Abstract
Pregabalin (PGL) is a gabapentinoid used to treat epilepsy, neuropathic pain and generalized anxiety disorder. PGL is also misused by heroin users as it enhances the effects of heroin. While it is thought those who misuse PGL take it in amounts greater than the recommended therapeutic dose, it is unknown whether there is a significant difference between the amounts of PGL used by heroin users compared to non-heroin users. This study hypothesized that the PGL concentrations in postmortem (PM) samples taken from heroin users positive for PGL would be higher than those in non-heroin users. Between 1 January 2016 and 31 December 2016, a routine drug screen and a specific screen for PGL were carried out on femoral-vein bloods from 3,750 PM Coroners’ cases. Of the cases screened, 354 were heroin users, of which 264 cases were negative for gabapentinoids and therefore used as the control-heroin-user group. PGL was positive in 229 cases, of which 69 were heroin users and 160 were non-heroin users. On comparing the PGL concentrations, statistically higher concentrations were observed in the heroin users compared to non-heroin users (P = 0.002). There was no correlation between the concentrations of PGL and morphine (from heroin) in the heroin users (P = 0.95), and the amount of heroin (morphine) consumed was not dependant on whether PGL was consumed or not (P = 0.98). The prevalence of anti-depressants, benzodiazepines, methadone and non-heroin-related opioids was seen to be significantly higher in heroin users that were positive for PGL than the control-heroin users (P = &lt; 0.001 for all drugs). This study suggests that heroin users are using greater amounts of PGL compared to non-heroin users; however, the magnitude of the difference in use may not be sufficient to conclude that heroin users are at substantially greater risk of PGL toxicity compared to non-heroin users. Results indicate that heroin users who take PGL are more likely to use multiple depressant drugs, hence increasing the risk of multi-drug toxicity and death in this population.
Hyperbaric Oxygen and Mortality in Burns With Inhalation Injury: A Study of the National Burn Repository
Authors: Nygaard Rachel M , Endorf Frederick W 
Published: June 2021

AbstractMortality in burn injury is primarily influenced by three factors: age, percent burn (%TBSA), and presence of inhalation injury. Numerous modalities have been tried in an attempt to treat those patients with burns and inhalation injury, including the use of hyperbaric oxygen (HBO). The aim of our study was to find the national prevalence of HBO for burns with inhalation injury, and whether HBO influenced mortality in these often severely injured patients. This retrospective study used the National Burn Repository (NBR) to identify hospital admissions of patients with both cutaneous burn and inhalation injuries. After applying exclusion criteria, a total of 13,044 patients were identified. Variables included in the multivariate regression analysis included age, sex, race, payer, mechanism of burn injury, TBSA group, total procedure number, mechanical ventilator days, and treatment with HBO. The main outcome variable was mortality. Of the 13,044 patients, 67 had HBO therapy. The HBO patients were older (mean age 51.7 vs 42.8 years, P &lt; .001), but had smaller burns and thus a similar Baux score (66.6 vs 65.2, P = .661). The HBO patients had a higher mortality (29.9% vs 17.5%, P = .01). On multivariate regression analysis, HBO was an independent predictor of mortality (odds ratio = 2.484, P = .004). Other significant predictors of mortality included age, black race, Medicaid or uninsured patients, and %TBSA. The use of HBO for patients with burns and inhalation injury is uncommon in this database. It is unclear whether that reflects low prevalence or if individual centers do not all impute HBO into the NBR. For those patients in this database, HBO is an independent predictor of mortality. It can be difficult to determine the severity of inhalation injury in the NBR, so those patients receiving HBO could theoretically have more severe inhalation injury.
Do Low-Risk Patients With Dyspepsia Need a Gastroscopy? Use of Gastroscopy for Otherwise Healthy Patients With Dyspepsia
Authors: Halasz Jennifer B , Burak Kelly W , Dowling Shawn K , Murray Brenna , Williams Jennifer , Misra Tarun , Veldhuyzen van Zanten Sander J , Kaplan Gilaad G , Swain Mark , Novak Kerri L 
Published: June 2021

Abstract

Background
Choosing Wisely Canada (CWC) recommends not to perform gastroscopy for dyspepsia in otherwise healthy adults less than 55 years of age (2014). The aim of this study was to evaluate the use of gastroscopy in a young, healthy population with uncomplicated dyspepsia.

Methods
A retrospective review of gastroscopies completed during 3-month periods in 2015, 2016, and 2017 identified all patients undergoing gastroscopy for the primary indication of dyspepsia. Low-risk patients for dyspepsia were defined as adults, aged 18 to 54 years without alarm symptoms, comorbidities and/or abnormal imaging findings or laboratory values. Gastroscopy and pathology reports were reviewed to identify clinically actionable findings. Clinical outcomes were followed to December 31, 2018 including gastroenterology referrals, emergency room visitation and hospitalization.

Results
Among 1358 patients having a gastroscopy for dyspepsia, 480 (35%) were low-risk patients. Sixteen patients 3.3% (16/480) had a clinically actionable result found on gastroscopy or biopsy. No malignant lesions were detected. Low-risk patients were followed up for an average of 2.75 years, 8% (39/480) visited the emergency department (ED), 1% (3/480) of patients were admitted to hospital and 12% (59/480) of patients were re-referred for a dyspepsia-related concern.

Interpretation
A high rate of low yield, high cost, invasive endoscopic investigations were performed in this population of otherwise healthy patients under age 55 years. These data suggest limited uptake of current recommendations against the routine use of gastroscopy to investigate dyspepsia.
Professor Arnold L. (Arny) Demain's historical position in the rise of industrial microbiology and biotechnology
Authors: Vandamme Erick J 
Published: June 2021

AbstractThis perspective text focuses on the pivotal role and historical position that the late Prof. Arnold L. (Arny) Demain has taken since the 1950s in the rise and impact of the field of industrial microbiology and biotechnology. His drive toward academic research with industrial potential—first at Merck & Co. and later at MIT—, his feeling for establishing cordial personal contacts with his students and postdocs (Arny's Army) and his ability for worldwide networking are outlined here, intertwined with the author's personal experiences and impressions. His scientific output is legendary as to research papers, comprehensive reviews, books, and lectures at conferences worldwide. Some of his research experiences in industry and academia are mentioned in a historical context as well as his relentless efforts to advocate the importance and impact of industrial microbiology and biotechnology as an essential green technology for our planet Earth.
Evaluation of the Residual Efficacy of Actellic300 CS in Simple Huts in Central Ethiopia
Authors: Dugassa Sisay , Mekonnen Sileshi , Muthee Peter W , Peter Rose , Zinyengere David , Feyasa Merga B , Sievert Kai 
Published: June 2021

Abstract
Indoor residual spraying (IRS) is one of the key vector control tools with a long history of use in the world. Ethiopia has set a goal to eliminate malaria from selected districts mainly by applying IRS and the distribution of long-lasting insecticidal nets. IRS is applied in low malaria transmission districts which are epidemic prone and in districts with high malaria transmission. Ethiopia uses insecticides that are recommended by World Health Organization; these insecticides must also be registered in Ethiopia. The registration of new and potential products requires confirmatory, local efficacy trials to be performed. Actellic 300CS, now registered, is one of such potential product. Actellic 300CS showed average mortalities of 99.6%, 99.6%, and 99.0% on the sprayed surfaces in the experimental huts, the top, middle, and bottom sections, respectively during the first 6 mo of the study period. Beyond 6 mo, (7, 8, and 9 mo) follow-up, mortalities for the top, middle, and bottom sections were 85.2%, 86.3%, and 85.2%, respectively. The results showed that the residual efficacy of Actellic 300CS was up to 9 mo with the first 6 mo exhibiting mortalities of greater than 99% while the next 3 mo showed mortalities exceeding 85%. Actellic 300CS was effective against fully susceptible laboratory-reared Anopheles arabiensis on all four surface types (rough, smooth, dung, and painted surfaces) tested in this study and could be used as one of the chemical insecticides of choice for the ongoing IRS programs in Ethiopia.
Effects of pulse precipitation on soil organic matter mineralization in forests: spatial variation and controlling factors
Authors: Jiang Zhaoxia , Bian Hongfeng , Xu Li , Li Mingxu , He Nianpeng 
Published: June 2021

Abstract

Aims
Pulse effects of precipitation cause soil organic matter to rapidly decompose and release CO2 in a short period. The pulse effects of precipitation are important for ecosystem C cycling and soil C balance, although their spatial variation in forest soils and the underlying mechanisms remain unclear.

Methods
Soil samples (0–10 cm) from 22 typical forest ecosystems in eastern China were used, to investigate the effects of simulated pulse precipitation on soil microbial respiration rates (Rs). We simulated pulsed precipitation to reach 65% water-holding capacity, the Rs was measured on a minute scale for 48 h.

Important Findings
Precipitation pulses can cause a rapid 1.70–38.12-fold increase in the rate of mineralized decomposing organic matter. Maximum Rs (Rs-soil-max), cumulative Rs (ARs-soil) and the time taken to arrive at the maximal Rs (TRs-soil-max) were significant differences among different soil samples. Furthermore, the pulse effects in different climate zones were significantly different. Rs-soil-max (11.701 µg C g−1soil h−1) and ARs-soil (300.712 µg C g−1 soil) were the highest in the mid-temperate zone. Soil chemical properties (total C and, N, pH and oxidation–reduction potential) and soil fractions were strongly correlated with the pulse effects in forest soils, but soil microbes contributed less. Our findings demonstrated that the pulse effects increase forest soil carbon emissions in the short term at a regional scale, and identified the factors with the greatest influence on this change. These findings help guide future studies on the C cycles of forest ecosystems and regulating ecosystem C cycles.