bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient and Provider Perspectives on Glaucoma Treatment Adherence: A Delphi Study in Urban Alabama
Authors: Poleon Shervonne , Racette Lyne , Fifolt Matthew , Schoenberger-Godwin Yu-Mei , Abu Sampson Listowell , Twa Michael D. 
Published: September 2021

SIGNIFICANCE
Patients with glaucoma and providers recognized perceived treatment efficacy, patient-provider relationship, psychological stress, instillation skill, good quality of life, and forgetfulness as key determinants of glaucoma adherence. This shared insight could help shape the development of clinical and behavioral interventions for addressing treatment barriers and improving adherence.

PURPOSE
Despite their impact on adherence in glaucoma, sociobehavioral factors may not be adequately explored during clinical consultations. We aimed to elicit consensus between patients and providers around key determinants of adherence and hypothesized that patients would place greater emphasis on sociobehavioral factors compared with providers.

METHODS
A two-round Delphi survey was used to assess treatment beliefs, barriers, facilitators, motivators, and needs among 18 patients with glaucoma and providers. In round 1, agreement with 46 statements was scored on a 5-point Likert scale (strongly disagree to strongly agree). Statements with which 80% or more of panelists agreed reached consensus and advanced to round 2, where participants were asked to prioritize them based on their importance to treatment.

RESULTS
There was consensus regarding the influence of perceived treatment efficacy, good provider relationship, good quality of life, psychological stress, glaucoma knowledge, instillation skill, and forgetfulness on glaucoma adherence. For statements that failed to reach consensus, the Bonferroni-corrected Mann-Whitney U test revealed that the greatest differences between patients and providers pertained to regimen complexity (provider median, 4 [interquartile range {IQR}, 1]; patient median, 1.5 [IQR, 1]; P = .002), instillation skill (providers, 4 [IQR, 0.5]; patients, 2 [IQR, 1]; P = .001), and low motivation (providers, 3 [IQR, 2.25]; patients, 1 [IQR, 0]; P = .003).

CONCLUSIONS
Although patients and providers prioritized sociobehavioral factors as key determinants of adherence, disagreement between these groups was observed in other areas. Continued juxtaposition of patient and provider perspectives could spotlight underexplored areas and guide the development of successful interventions for improving adherence.
Case Report: Multimodal Imaging of Acute Idiopathic Maculopathy in a Chinese Woman
Authors: Zhang Ke , Liu Jian , Jiang Deyong , Myers Frank L. , Zhou Liang 
Published: September 2021

SIGNIFICANCE
Acute idiopathic maculopathy is a rare disease with the characteristics of sudden, severe, unilateral central vision loss after a flu-like illness. The prognosis is generally good, and poor vision usually results from complications such as choroidal neovascularization or subfoveal pigment degeneration. Multimodal imaging is helpful in the diagnosis and follow-up of this disease.

PURPOSE
We report a case of acute idiopathic maculopathy and present multimodal imaging results in the diagnosis of this condition.

CASE REPORT
A 37-year-old Chinese woman noted a central scotoma in her right eye a day after a prodrome of flu-like symptoms. Best-corrected visual acuity of the right eye was 20/40. Multimodal imaging was performed, and a diagnosis of acute idiopathic maculopathy was made. The variable clinical appearance of acute idiopathic maculopathy on autofluorescence, near-infrared reflectance, and optical coherence tomography (OCT) was shown. The patient's vision spontaneously recovered to 20/20 two weeks after the onset of the disease, but macular sensitivity, as measured by microperimetry, did not return to normal until 1 month. Retrobulbar injection of triamcinolone was done at 3 weeks to prevent retinal pigment epithelium hyperplasia and choroidal neovascularization. Written informed consent was obtained from the patient.

CONCLUSIONS
Our findings suggest that near-infrared reflectance corresponds to the change of the outer retina and retinal pigment epithelium on OCT and complements autofluorescence in the diagnosis and follow-up of acute idiopathic maculopathy. Fundus autofluorescence, near-infrared reflectance, and OCT are recommended as routine examinations in this disease.
BCL11A intellectual developmental disorder: defining the clinical spectrum and genotype-phenotype correlations
Authors: Peron Angela , D’Arco Felice , Aldinger Kimberly A. , Smith-Hicks Constance , Zweier Christiane , Gradek Gyri A. , Bradbury Kimberley , Accogli Andrea , Andersen Erica F. , Au Ping Yee Billie , Battini Roberta , Beleford Daniah , Bird Lynne M. , Bouman Arjan , Bruel Ange-Line , Busk Øyvind Løvold , Campeau Philippe M. , Capra Valeria , Carlston Colleen , Carmichael Jenny , Chassevent Anna , Clayton-Smith Jill , Bamshad Michael J , Earl Dawn L. , Faivre Laurence , Philippe Christophe , Ferrerira Patrick , Graul-Neumann Luitgard , Green Mary J. , Haffner Darrah , Haldipur Parthiv , Hanna Suhair , Houge Gunnar , Hurst Jane , Kraus Cornelia , Kristiansen Birgit Elisabeth , Lespinasse James , Low Karen J. , Lynch Sally Ann , Maia Sofia , Mao Rong , Marcinkute Ruta , Melver Catherine , McDonald Kimberly , Montgomery Tara , Morleo Manuela , Motter Constance , Openshaw Amanda S. , Palumbos Janice Cox , Parikh Aditi Shah , Person Richard , Desai Megha , Piard Juliette , Pfundt Rolph , Scala Marcello , Serey-Gaut Margaux , Slavotinek Anne , Suri Mohnish , Turner Claire , Tvrdik Tatiana , Weiss Karin , Wentzensen Ingrid M. , Zollino Marcella ,   C4RCD Research Group,   Telethon Undiagnosed Disease Program (TUDP),   University of Washington Center for Mendelian Genomics (UW-CMG), de Vries Bert B.A. , Guillemot Francois , Dobyns William B. , Viskochil David , Dias Cristina 
Published: September 2021

AbstractPurposeHeterozygous variants in BCL11A underlie an intellectual developmental disorder with persistence of fetal hemoglobin (BCL11A-IDD, a.k.a. Dias-Logan syndrome). We sought to delineate the genotypic and phenotypic spectrum of BCL11A-IDD.MethodsWe performed an in-depth analysis of 42 patients with BCL11A-IDD ascertained through a collaborative network of clinical and research colleagues. We also reviewed 33 additional affected individuals previously reported in the literature or available through public repositories with clinical information.ResultsMolecular and clinical data analysis of 75 patients with BCL11A-IDD identified 60 unique variants (30 frameshift, 7 missense, 6 splice-site, 17 stop-gain) and 8 unique CNVs (microdeletions involving BCL11A only). We redefined the most frequent manifestations of the condition: intellectual disability, hypotonia, behavioral abnormalities, postnatal microcephaly and autism spectrum disorder. Two thirds of patients have brain MRI abnormalities, and we identified a recurrent posterior fossa phenotype of vermian hypoplasia and/or small brainstem. Truncating BCL11A variants, particularly those affecting the long (BCL11A-L) and extra-long (-XL) isoforms, sparing the short (-S) isoform, were associated with increased severity.ConclusionsWe expand the clinical delineation of BCL11A-IDD and identify a potential isoform-specific genotype-phenotype correlation. We show that BCL11A-IDD is associated with posterior fossa anomalies and highlight the differences between BCL11A-IDD and 2p16.1p15 microdeletion syndrome.
COVID-19 convalescent plasma and randomized clinical trials: explaining conflicting outcomes and finding signals of efficacy
Authors: Focosi Daniele , Franchini Massimo , Pirofski Liise-anne , Burnouf Thierry , Paneth Nigel , Joyner Michael J. , Casadevall Arturo 
Published: September 2021

AbstractConvalescent plasma (CP) recurs as a frontline treatment in epidemics because it is available as soon as there are survivors. The COVID-19 pandemic represented the first large-scale opportunity to shed light into mechanisms of action, safety and efficacy of CP using modern evidence-based medicine approaches. Studies ranging from observational case series to randomized controlled trials (RCT) have reported highly variable efficacy results for COVID-19 CP (CCP), resulting in uncertainty. Reasons for CCP success and failure may be hidden in study details, which are usually difficult to explain to physicians and the public but provide fertile ground for designing next-generation studies. We analyzed variables associated with efficacy such as clinical settings, disease severity, CCP SARS-CoV-2 antibody levels and function, dose, timing of administration (variously defined as time from onset of symptoms, molecular diagnosis, diagnosis of pneumonia, or hospitalization, or by serostatus), outcomes (defined as hospitalization, requirement for ventilation, clinical improvement or mortality), CCP provenance and time for collection, and criteria for efficacy. Focusing only on the results from the 30 available RCTs we noted that these were more likely to show signals of efficacy, including reductions in mortality, if the plasma neutralizing titer was ≥ 160 and the time to randomization was ≤ 9 days, consistent with passive antibody therapy efficacy requiring dosing with sufficient antibody. The fact that most studies revealed signals of efficacy despite variability in CCP and its use suggest likely therapeutic effects that become apparent despite the data noise. Despite the recent WHO guidelines discouraging CCP usage, the Omicron variant of concern is reminding us the superiority of polyclonal antibody therapies over monoclonal antibodies, and CCP from vaccinated convalescents is likely to be evaluated soon
Antibody kinetics to SARS-CoV-2 at 13.5 months, by disease severity
Authors: Violán Concepción , Torán Pere , Quirant Bibiana , Lamonja-Vicente Noemi , Carrasco-Ribelles Lucía A. , Chacón Carla , Manresa-Dominguez Josep Maria , Ramos-Roure Francesc , Roso-Llorach Albert , Pujol Aleix , Ouchi Dan , Monteagudo Mónica , Montero Pilar , Garcia-Sierra Rosa , Arméstar Fernando , Dacosta-Aguayo Rosalia , Doladé Maria , Prat Nuria , Bonet Josep Maria , Clotet Bonaventura , Blanco Ignacio , Prado Julia G , Martínez Cáceres Eva María ,   for the ProHEpiC-19 Investigators
Published: September 2021

ABSTRACTBackgroundUnderstanding humoral responses and seroprevalence in SARS-CoV-2 infection is essential for guiding vaccination strategies in both infected and uninfected individuals.MethodsWe determine the kinetics of IgM against the nucleocapsid (N) and IgG against the spike (S) and N proteins of SARS-CoV-2 in a cohort of 860 health professionals (healthy and infected) in northern Barcelona. We model the kinetics of IgG and IgM at nine time points over 13.5 months from infection, using non-linear mixed models by sex and clinical disease severity.ResultsOf the 781 participants who were followed up, 478 (61.2%) became infected with SARS-CoV-2. Significant differences were found for the three antibodies by disease severity and sex. At day 270 after diagnosis, median IgM(N) levels were already below the positivity threshold in patients with asymptomatic and mild-moderate disease, while IgG(N, S) levels remained positive to days 360 and 270, respectively. Kinetic modelling showed a general rise in both IgM(N) and IgG(N) levels up to day 30, followed by a decay whose rate depended on disease severity. IgG(S) levels increased at day 15 and remained relatively constant over time.ConclusionsWe describe kinetic models of IgM(N) and IgG(N, S) SARS-CoV-2 antibodies at 13.5 months from infection and disease spectrum. Our analyses delineate differences in the kinetics of IgM and IgG over a year and differences in the levels of IgM and IgG as early as 15 days from symptoms onset in severe cases. These results can inform public health policies around vaccination criteria.Funded by the regional Ministry of Health of the Generalitat de Catalunya (Call COVID19-PoC SLT16_04; NCT04885478)
Children and adults with mild COVID-19 symptoms develop memory T cell immunity to SARS-CoV-2
Authors: Kaaijk Patricia , Pimentel Verónica Olivo , Emmelot Maarten E. , Poelen Martien , Cevirgel Alper , Schepp Rutger M. , den Hartog Gerco , Reukers Daphne F.M. , Beckers Lisa , van Beek Josine , van Els Cécile A.C.M. , Meijer Adam , Rots Nynke Y. , de Wit Jelle 
Published: September 2021

AbstractBackgroundSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to considerable morbidity/mortality worldwide, but most infections, especially among children, have a mild course. However, it remains largely unknown whether infected children develop cellular immune memory.MethodsTo determine whether a memory T cell response is being developed as an indicator for long-term immune protection, we performed a longitudinal assessment of the SARS-CoV-2-specific T cell response by IFN-γ ELISPOT and activation marker expression analyses of peripheral blood samples from children and adults with mild-to-moderate COVID-19.ResultsUpon stimulation of PBMCs with heat-inactivated SARS-CoV-2 or overlapping peptides of spike (S-SARS-CoV-2) and nucleocapsid proteins, we found S-SARS-CoV-2-specific IFN-γ T cell responses in most infected children (83%) and all adults (100%) that were absent in unexposed controls. Frequencies of SARS-CoV-2-specific T cells were higher in infected adults, especially in those with moderate symptoms, compared to infected children. The S-SARS-CoV-2 IFN-γ T cell response correlated with S1-SARS-CoV-2-specific serum IgM, IgG, and IgA antibody concentrations. Predominantly, effector memory CD4+ T cells of a Th1 phenotype were activated upon exposure to SARS-CoV-2 antigens, which persisted for 4-8 weeks after symptom onset. We detected very low frequencies of SARS-CoV-2-reactive CD8+ T cells in these individuals.ConclusionsOur data indicate that an antigen-specific memory CD4+ T cell response is induced in children and adults with mild SARS-CoV-2 infection. T cell immunity induced after mild COVID-19 could contribute to protection against re-infection.
The Morbidity Costs of Air Pollution through the Lens of Health Spending in China
Authors: Zhang Xin , Zhang Xun , Chen Xi , Liu Yuehua , Zhao Xintong 
Published: September 2021

AbstractThis study offers one of the first causal evidence on the morbidity costs of fine particulates (PM2.5) for all age cohorts in a developing country, using individual-level healthcare spending data from the basic medical insurance program in Wuhan, China. Our instrumental variable (IV) approach uses thermal inversion to address potential endogeneity in PM2.5 concentrations and shows that PM2.5 imposes a significant impact on medical expenditures. The IV estimate suggests that a 10 μg/m3 reduction in monthly average PM2.5 leads to a 2.79% decrease in the value of health spending and a 0.70% decline in the number of transactions in pharmacies and health facilities. The effect is more salient for males, children, and older adults. Moreover, our estimates provide a lower bound of people’s willingness-to-pay, which amounts to CNY 51.85 (or USD 8.38) per capita per year for a 10 μg/m3 reduction in PM2.5.JEL CodesQ51, Q53, I11, I31Conflict of interestThe authors declare that they have no conflict of interest.
An almost nontoxic tetrodotoxin analog, 5,6,11-trideoxytetrodotoxin, as an odorant for the grass puffer
Authors: Noguchi Yoshihisa , Suzuki Takehisa , Matsutani Keigo , Sakakibara Ryo , Nakahigashi Ryota , Adachi Masaatsu , Nishikawa Toshio , Abe Hideki 
Published: September 2021

AbstractToxic puffers contain the potent neurotoxin, tetrodotoxin (TTX). Although TTX is considered to serve as a defense substance, previous behavioral studies have demonstrated that TTX acts as an attractive pheromone for some toxic puffers. To elucidate the physiological mechanism of putative pheromonal action of TTX, we examined whether grass puffers Takifugu alboplumbeus can detect TTX. Electroolfactogram (EOG) results suggest that the olfactory epithelium (OE) of grass puffers responded to a type of TTX analog (5,6,11-trideoxyTTX), although it did not respond to TTX. We also examined the attractive action of 5,6,11-trideoxyTTX on grass puffers by recording their swimming behavior under dark conditions. Grass puffers preferred to stay on the side of the aquarium where 5,6,11-trideoxyTTX was administered, and their swimming speed decreased. Additionally, odorant-induced labeling of olfactory sensory neurons by immunohistochemistry against neural activity marker (phosphorylated extracellular signal regulated kinase; pERK) revealed that labeled olfactory sensory neurons were localized in the region surrounding “islets” where there was considered as nonsensory epithelium. 5,6,11-trideoxyTTX has been known to accumulate in grass puffers, but its toxicity is much lower (almost nontoxic) than TTX. Our results suggest that toxic puffers may positively use this TTX analog, which has been present in their body with TTX but whose function was unknown, as an odorant for chemical communication or effective TTX accumulation.
Fragment-based ab initio phasing of peptidic nanocrystals by MicroED
Authors: Richards Logan S. , Flores Maria D. , Millán Claudia , Glynn Calina , Zee Chih-Te , Sawaya Michael R. , Gallagher-Jones Marcus , Borges Rafael J. , Usón Isabel , Rodriguez Jose A. 
Published: September 2021

AbstractMicrocrystal electron diffraction (MicroED) is transforming the visualization of molecules from nanocrystals, rendering their three-dimensional atomic structures from previously unamenable samples. Peptidic structures determined by MicroED include naturally occurring peptides, synthetic protein fragments and peptide-based natural products. However, as a diffraction method, MicroED is beholden to the phase problem, and its de novo determination of structures remains a challenge. ARCIMBOLDO, an automated, fragment-based approach to structure determination. It eliminates the need for atomic resolution, instead enforcing stereochemical constraints through libraries of small model fragments, and discerning congruent motifs in solution space to ensure validation. This approach expands the reach of MicroED to presently inaccessible peptidic structures including segments of human amyloids, and yeast and mammalian prions, and portends a more general phasing solution while limiting model bias for a wider set of chemical structures.
Amelioration of L-DOPA-induced dyskinesia with vitamin D3in Parkinsonian mice model
Authors: Bayo-Olugbami Adedamola Aminat , Nafiu Abdulrazaq Bidemi , Amin Abdulbasit , Ogundele Olalekan Michael , Lee Charles C. , Owoyele Bamidele Victor 
Published: September 2021

AbstractL-DOPA Induced Dyskinesia (LID) is associated with prolonged L-DOPA therapy. Vitamin-D receptor modulation improves motor-cognitive deficit in experimental LID Parkinsonism. Therefore, in this study, we investigated the mechanism underlying the anti-dyskinetic potential of Vitamin D3 (VD3). Dyskinesia was induced by chronic L-DOPA administration in 6-OHDA lesioned male C57BL6 mice. The experimental groups (Dyskinesia, Dyskinesia/VD3, and Dyskinesia/Amantadine) and controls were challenged with L-DOPA to determine the abnormal involuntary movements (AIMs) score during 14 days of VD3(30 mg/kg) or Amantadine (40 mg/kg) treatment. Global behavioral Axial, Limb & Orolingual (ALO) AIMs were scored for 1 min at every 20 mins interval, over a duration of 100 mins on days 1,3,7,11 and 14 of treatment. Thereafter, brain samples were collected and processed for immunoblotting to assess striatal expression of tyrosine hydroxylase (TH), monoamine oxidase (MAO), cathecol-o-methyl transferase (COMT), dopamine decarboxylase (DDC), CD11b, BAX, P47phox, and IL-1β. VD3significantly attenuated ALO AIMs only on days 11 & 14, with maximal reduction of 32.7% compared with dyskinetic mice but had no effect on days 1, 3 & 7, while amantadine decreased AIMs all through days 1 to 14 with maximal reduction of 64.5%. TH and MAO-B expression were not significantly different across the groups. DDC was significantly suppressed in dyskinetic micevscontrol (p<0.001) but remained unchanged in VD3micevsdyskinetic mice. COMT was upregulated in the dyskinetic groupvscontrol (p<0.01) and attenuated in VD3mice (p<0.05) compared to the dyskinetic group. Interestingly, VD3inhibited significantly (p<0.01) oxidative stress (p47phox), apoptosis (BAX), inflammation (IL-1β), and microglial activation (CD11b) in dyskinetic mice. Overall, we find that the anti-dyskinetic effects of VD3is associated with modulation of striatal oxidative stress, microglial responses, inflammation, and apoptotic signaling.Impact statementThere are evidences showing that VD3supplementation improves motor disorders, including Parkinson’s disease. We hypothesized that VD3could improve LID, an abnormal involuntary movement that results from prolonged L-DOPA therapy in the management of PD. We have demonstrated the novel anti-dyskinetic effect of VD3and associated mechanistic factors in a mouse model of L-DOPA Induced Dyskinesia (LID), which identifies promising targets for dyskinesia therapy.
Remote immune processes revealed by immune-derived circulating cell-free DNA
Authors: Fox-Fisher Ilana , Piyanzin Sheina , Ochana Bracha-Lea , Klochendler Agnes , Magenheim Judith , Peretz Ayelet , Loyfer Netanel , Moss Joshua , Cohen Daniel , Drori Yaron , Friedman Nehemya , Mandelboim Michal , Rothenberg Marc E. , Caldwell Julie M. , Rochman Mark , Jamshidi Arash , Cann Gordon , Lavi David , Kaplan Tommy , Glaser Benjamin , Shemer Ruth , Dor Yuval 
Published: September 2021

AbstractBlood cell counts often fail to report on immune processes occurring in remote tissues. Here we use immune cell type-specific methylation patterns in circulating cell-free DNA (cfDNA) for studying human immune cell dynamics. We characterized cfDNA released from specific immune cell types in healthy individuals (N=242), cross sectionally and longitudinally. Immune cfDNA levels had no individual steady state as opposed to blood cell counts, suggesting that cfDNA concentration reflects adjustment of cell survival to maintain homeostatic cell numbers. We also observed selective elevation of immune-derived cfDNA upon perturbations of immune homeostasis. Following influenza vaccination (N=92), B-cell-derived cfDNA levels increased prior to elevated B-cell counts and predicted efficacy of antibody production. Patients with Eosinophilic Esophagitis (N=21) and B-cell lymphoma (N=27) showed selective elevation of eosinophil and B-cell cfDNA respectively, which were undetectable by cell counts in blood. Immune-derived cfDNA provides a novel biomarker for monitoring immune responses to physiological and pathological processes that are not accessible using conventional methods.