bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-term impact of the COVID-19 pandemic on a population-based screening program for colorectal cancer in Catalonia (Spain)
Authors: Nuria Vives , Gemma Binefa , Carmen Vidal , Núria Milà , Rafael Muñoz , Virtudes Guardiola , Rial O , Garcia Montse Vidal 
Published: June 2021

Abstract
Background
By mid-March 2020, colorectal cancer (CRC) screening program in Catalonia was suspended at all levels. Our goal was to assess the short-term impact of the COVID-19 pandemic at a FIT-based CRC screening hub in the metropolitan area of Barcelona.
Methods
Short-term impact was measured in individuals invited between 1 January and 12 March 2020: screening participation, colonoscopy adherence, interval from positive test result to colonoscopy and psychological distress.
Results
Lockdown with the first wave of COVID-19 caused 111,000 individuals to defer their screening invitations. Participation among invitees between January - March 2020 was 39.3% (95% CI: 38.9–39.7), a decrease of 5% in comparison with the 41.4% (95% CI: 41.2–41.6) participation in 2019. Adherence to colonoscopy decreased from 89.3% (95% CI: 88.4–90.2) in 2019 to 81.4% (95% CI: 78.9–83.7) in the first quarter of 2020. The mean time to colonoscopy after resumption was 128.7 days (CI 95%: 125.3–132.2). Irrespective of test results, factors associated with higher levels of distress were a greater perceived risk of CRC and greater impairment of emotional wellbeing due to COVID-19.
Conclusions
The short-term impact of COVID-19 on CRC screening seems to have been modest, with a slight decrease in participation, a moderate decrease in colonoscopy adherence, and lengthened waiting times. However, a marked impact on future CRC incidence and deaths could be expected. Thus, it is critical to revert participation and colonoscopy adherence rates to that previously achieved while reducing the 5-month delay in screening invitations.
Long-Term Safety and Effectiveness of Velaglucerase Alfa in Gaucher Disease: 6-Year Interim Analysis of A Post-Marketing Surveillance in Japan
Authors: Sagara Rieko , Ishigaki Masahide , Otsuka Manami , Murayama Kei , Ida Hiroyuki , Fernandez Jovelle 
Published: June 2021

Abstract
Background
Gaucher disease (GD) is caused by reduced lysosomal enzyme β-glucocerebrosidase activity. Heterogeneous genotypes and phenotypes have been observed within GD types and across ethnicities. Enzyme replacement therapy is generally recommended for patients with Type 1 GD, the least severe form of GD. In Japan, velaglucerase alfa has a broad indication covering Type 1, 2 or 3 GD.
Methods
All patients with Type 1, 2, or 3 GD administered velaglucerase alfa 60 U/kg every 2 weeks via intravenous infusion after its launch date in Japan in 2014, were enrolled in a non-interventional, observational post-marketing surveillance (PMS). Individual patient data were reported via case report forms (CRFs). Key safety endpoints investigated included the incidence of infusion-related reactions (IRRs), the safety of velaglucerase alfa in patients with Types 2 and 3 GD, from patients under one year of age to elderly patients (≥ 65 years of age). Long-term efficacy was also assessed.
Results
In total, 53 patients with GD were registered. CRFs were available for 41 (77.4%) patients at the 6-year interim analysis. Fourteen adverse drug reactions (ADRs) were reported in seven patients. All reported ADRs occurred in patients with Type 2 GD. ADRs were reported by 63.6% (7/11) of patients with Type 2 GD. Ten ADRs were reported in five patients aged < 4 years. No elderly patients experienced any ADR during the surveillance period. Five ADRs occurring in three (10.0%) patients were classified as IRRs, with one case of vomiting (moderate severity) resulting in treatment discontinuation. Ten serious adverse events were reported in five (16.7%) patients. Three fatal events were considered to be unrelated to treatment with velaglucerase alfa. Platelet counts increased after the administration of velaglucerase alfa and were generally maintained within the normal range over the administration period. Among eleven patients tested for neutralizing anti-velaglucerase alfa antibodies, two (18.2%) were assessed as positive results.
Conclusion
PMS data from patients with Types 1–3 GD in Japan indicate that long-term treatment with velaglucerase alfa was well-tolerated and associated with increased platelet counts, which is consistent with observations made in studies outside of Japan.
Trial registration:
NCT03625882 registered July 2014.
Determining Sex-based Differences in Inflammatory Response in an Experimental Traumatic Brain Injury Model
Authors: Scott Michael Collins , Prabhakara Karthik , Walters Andrew J. , Olson Scott D. , Cox Charles S. 
Published: June 2021

Abstract
Introduction: Traumatic brain injury is a leading cause of injury-related death and morbidity. Despite multiple clinical and pre-clinical studies, sex-based differences in blunt TBI outcomes based remain unclear. Our accepted rodent model of blunt traumatic brain injury was used to identify differences in the pathological features of blunt TBI. Methods: Male and female Sprague-Dawley rats were subjected to either controlled-cortical impact (CCI) or sham injury; brain tissue was harvested at different time intervals depending on the specific study. Blood-brain barrier (BBB) analysis was performed using Alexa Fluor 680 dye. Microglia and splenocytes were characterized with traditional flow cytometry; microglia markers such as CD45, P2Y12, CD32, and CD163 were analyzed with t-distributed stochastic neighbor embedding (t-SNE). Flow cytometry was used to study tissue cytokine levels, and supplemented with ELISAs of TNF-⍺, IL-17, and IL-1β of the ipsilateral hemisphere tissue were performed. Results: CCI groups had an increase in BBB permeability in both sexes. There was significant difference in the integrated density value of BBB permeability between the male CCI group and the female CCI group (female CCI mean = 3.08 x 108 ± 2.83 x 107, male CCI mean = 2.20 x 108 ± 4.05 x 106, p = 0.0210), but otherwise no differences were observed. Traditional flow cytometry did not distinguish any sex-based difference in regards to splenocyte cell population after CCI. t-SNE did not reveal any significant difference between the male and female injury groups in the activation of microglia. Cytokine analysis after injury by flow cytometry and ELISA did not reveal any significant differences between sex. Conclusion: In our rodent model of blunt traumatic brain injury, sex-based differences in pathology and neuroinflammation are limited, and only noted in one specific analysis of BBB permeability.
Correlation of Peripheral CD4+GranzB+CTLs with Disease Severity in Patients with Primary Sjögren’s Syndrome
Authors: Wang Qi , Che Nan , Lu Chenyin , Sun Xiaoxuan , Wang Yanyan , Wang Qiang , Tan Wenfeng , Zhou Lanlan , Zhang Xiaojun , Xu Dong , Gu Lei , Zhang Miaojia 
Published: June 2021

Abstract
Introduction: The major histopathologic lesion of SS is a focal lymphocytic infiltrate, which include a majority of CD4+T. Several studies have shown that the epithelial cells in SS present diverse phenomena, such as MHC class II overexpression. CD4+T cells with cytotoxic activity are characterized by their ability to secrete granzyme B to kill the target cells in an MHC class II-restricted fashion. So this study was to investigate the correlation of peripheral CD4+GranzB+CTLs with pSS. Methods: We recruited 116 pSS and 46 HC using flow cytometry to examine the percentage of CD4+GranzB+CTLs in peripheral blood, and immunofluorescence to test their expression in labial gland. Results: The percentage of CD4+GranzB+CTLs were significantly up-regulated in pSS than HC (7.1±4.9% vs 3.1±1.9%, p <0.0001) and positive correlation with ESSDAI. The frequency of them were markedly higher in pSS with extraglandular manifestations. After excluding the other risk factors associated with pSS, they were still related to ESSDIA and extraglandular manifestations independently(p<0.05) and they are the risk factor of extraglandular involvement (odds ratio=1.928). Moreover, They could be observed in the LSGs. ROC curve analysis indicated that the area under the curve (AUC) of CD4+GranzB+CTLs was 0.796 to predict the activity of pSS, and 0.851 to presume extraglandular manifestations. The best diagnostic cut-off point was 4.865 for pSS patients. Conclusion: In this study, We provide new evidence indicating involvement of CD4+GranzB+CTLs over activation in the pathophysiology of pSS, which may serve as a new biomarker to evaluate the activity and severity of pSS.
Predicting Intestinal Viability After Acute Mesenteric Ischemia by Photoacoustic Imaging: An Experimental Study in Rats
Authors: Sugiura Takumi , Okumura Kenichiro , Matsumoto Junichi , Sakaguchi Maki , Komori Takahiro , Ogi Takahiro , Inoue Dai , Koda Wataru , Kobayashi Satoshi , Gabata Toshifumi 
Published: June 2021

Abstract
Our purpose was to assess the ability of photoacoustic imaging (PAI) to objectively predict ischemic intestinal pathological damage during surgery for acute mesenteric ischemia (AMI). PAI uses laser light to detect relative amounts of oxygenated and deoxygenated hemoglobin in intestinal tissue. In 18 rats, AMI was induced by clamping the mesenteric and marginal vessels of the ileum for 0 minutes in the sham group (n = 6), 30 minutes in the mild group (n = 6), and 180 minutes in the severe group (n = 6). After 60 minutes of reperfusion, the damage of the intestine was evaluated pathologically. Oxygenation of the intestine was monitored throughout the procedure in real time by the PAI system and compared between the mild and severe groups. All rats showed irreversible (i.e. transmucosal or transmural infarction) damage in the severe group. After reperfusion, the oxygenation in the mild group recovered immediately and was significantly higher than in the severe group at 1, 5, 10, 30, and 60 minutes (P = .007, 014, 016, 008, and 003, respectively). Oxygenation showed a significant strong negative correlation with the pathological severity. In conclusion, PAI could objectively predict irreversible ischemic damage immediately after reperfusion, which potentially prevents inadequate surgery.
Evaluation of a Breastmilk Hand Expression Toolkit: The M.I.L.K Survey Study
Authors: Alibhai Kameela Miriam , Murphy Malia SQ , Dunn Sandra , Keely Erin , O’Meara Paloma , Anderson Josdalyne , El-Chaâr Darine 
Published: June 2021

Abstract
Background: Breastmilk hand expression (BMHE) is recommended to promote lactation, relieve breast engorgement, and collect milk for future infant feedings. Resources to teach this skill are limited and infrequently developed in partnership with the obstetrical population. In collaboration with maternity care experts and individuals with recent breastfeeding experience, we designed a one-page toolkit that describes the process of BMHE and includes step-by-step instructions and images to illustrate the technique. This study aimed to evaluate the readability, clarity of content, layout, and informational value of this BMHE toolkit. Methods: Individuals who intended to breastfeed, were currently breastfeeding, or had recently breastfed were electronically surveyed between November 2020 and March 2021. The two-part survey consisted of radio, multi-select, Likert scale, and open-ended questions. Part one captured sociodemographic factors, obstetrical history, and breastfeeding practices. Part two collected feedback on the BMHE toolkit. Participant characteristics and feedback were summarized using descriptive statistics. Categorical and continuous variables were summarized using frequencies and percentages, and means and standard deviations, respectively. Results: Of the 123 participants, 117 (95.1%) had heard of hand expression prior to reviewing the toolkit and 99 (80.5%) had hand expressed before. Among the 48 participants who were no longer exclusively breastfeeding at the time of the survey, 22 (45.8%) had exclusively breastfed their infant for at least six months and 7 (14.6%) had discontinued exclusive breastfeeding within the first month. When asked about the BMHE toolkit, 118 (95.9%) participants said it was informative, 115 (93.5%) said it was easy to understand, and 114 (92.7%) said it was well laid-out. When asked about information seeking behaviours, participants indicated a preference for online resources (58.5%) and video resources (22.0%).Conclusion: The BMHE toolkit was well received by participants and the feedback was favourable overall. The survey feedback will be used to create a revised version of the toolkit that has been validated by the obstetrical patient population. Future research should focus on identifying implementation strategies to optimize the use of the toolkit and increase its effectiveness as an educational resource to correctly teach BMHE.
Safety and Efficacy of IL-6 Inhibitors in the Treatment of Neuromyelitis Optica Spectrum Disorders. A Meta-analysis
Authors: Kharel Sanjeev , Shrestha Suraj , Ojha Rajeev , Guragain Neha , Ghimire Rakesh 
Published: June 2021

Abstract
BackgroundInterleukin-6 (IL-6) inhibitors like Tocilizumab and Satralizumab are showing promising results in the treatment of Neuromyelitis Optica spectrum disorder (NMOSD). We aimed to investigate the efficacy and safety of various IL-6 inhibitors in the management of NMO/NMOSD.MethodsPubMed, Embase, and The Cochrane Library were systematically searched for suitable studies. Change in Annualized Relapse Ratio (ARR), Change in Extended Disability Status Scale (EDSS) s, the proportion of relapse-free patients, on trial relapse risk, and proportion of patients with adverse events, including serious adverse events and mortality were the parameters considered for the meta-analysis. Mean difference (MD) with 95% CI was used to quantify the change in ARR and change in EDSS-before and after treatment. While pooled risk ratio between the intervention group and placebo group was used in Randomized Controlled Trial (RCTs). A forest plot was prepared to indicate the efficacy outcomes.Results A total of nine studies with 202 patients were included in our meta-analysis. IL-6 inhibitors found a good proportion (75%,95% CI: 0.62–0.89; p<0.001) of relapse free patients at follow up. It also significantly reduced mean ARR (mean difference: -2.6 95% CI: -2.71 to -1.68; p<0.001) and on trial relapse risk (RR: 0.46; 95% CI: 0.32‐0.66; P< 0.001) but did not show significant difference in change in EDSS score (mean difference=-0.79, 95% CI: -1.89 to -0.31; p=0.16). Also, the toxicity profile of IL-6 inhibitors was acceptable considering the proportions of patients with adverse events (72%, 95% C.I.;0.59-0.84, I2=85.29%, p<0.001), proportions of patients with serious adverse events (18%;95% C.I.; -3.68 to 4.04, I2=0%, p=0.93) and zero treatment related deaths. In subgroup analysis, we found subcutaneous administration to be superior (81%;95% CI:0.74-0.82) than intravenous route (67%; 95% CI:0.67-0.89) in relapse free maintenance.ConclusionIL-6 inhibitor therapy showed significant benefits in reducing mean ARR, relapse risk and increasing the number of relapse-free patients with acceptable adverse events profile.
Dynamical Piezomagnetic Effect in Time-Reversal-Invariant Weyl Semimetals with Axionic Charge-Density Waves
Authors: Yu Jiabin , Wieder Benjamin , Liu Chao-xing 
Published: June 2021

Abstract
We predict that dynamical strain can induce a bulk orbital magnetization in time-reversal- (TR-) invariant Weyl semimetals (WSMs) that are gapped by charge-density waves (CDWs) -- a class of systems experimentally observed this past year.
We term this effect the ``dynamical piezomagnetic effect" (DPME).
By studying the low-energy effective theory and a minimal tight-binding (TB) model, we find that the DPME originates from an effective valley axion field that couples the electromagnetic gauge field with a strain-induced pseudo-gauge field.
In particular, the DPME represents the first example of a fundamentally 3D strain effect originating from the Chern-Simons 3-form, in contrast to the previously-studied piezoelectric effects characterized by 2D Berry curvature.
We further find that the DPME has a discontinuous change when the surface of the system undergoes a topological quantum phase transition (TQPT), and thus, that the DPME provides a bulk signature of a boundary TQPT in a TR-invariant Weyl-CDW.
Calibration-free NGS Quantitation of Mutations below 0.01% VAF
Authors: Dai Peng , Wu Lucia , Chen Sherry , Wang Michael , Chen Lauren , Zhang Jinny , Hao Christina , Yao Weijie , Zarka Jabra , Issa Ghayas , Kwong Lawrence , Zhang David 
Published: June 2021

Abstract
The quantitation of rare somatic mutations is essential for basic research and translational clinical applications including minimal residual disease (MRD) detection. Though unique molecular identifier (UMI) has suppressed sequencing error and allowed detection rare mutation, the sequencing depth requirement is high. The blocker displacement amplification (BDA) allele enrichment method allows detection of rare mutations using low sequencing depth, but requires calibration to accurately quantitate the VAF of novel mutations. Here, we present Quantitative Blocker Displacement Amplification (QBDA), a method that allows accurate detection and quantitation of mutations below 0.01% VAF at only 23,000X depth. QBDA integrates sequence-selective variant enrichment into UMI quantitation allowing confident detection of rare mutations and reduced sequencing depth. Using a panel of 20 genes recurrently altered in acute myeloid leukemia, we demonstrate quantitation of various mutations including single base substitutions and indels down to a VAF of 0.001% at a single locus with less than 4 million sequencing reads, allowing a sensitive minimal residual disease (MRD) detection in patients during complete remission. In a comprehensive pan-cancer panel covering 61 genes and a melanoma hotspot panel covering 8 genes, we detect mutations down to 0.1% VAF using only 1 million reads in a broad range of clinical samples including cell-free DNA and FFPE DNA, enabling tissue or liquid biopsy genetic tests with de-centralized sequencing instruments. QBDA ﻿thus provides a convenient and versatile method for sensitive mutation quantitation using low-depth sequencing.
Genetic and Metabolomic Differentiation of Physalis Ixocarpa Brot. Populations in Michoacan State, Mexico
Authors: Martínez-Vega Ariana , Oregel-Zamudio Ernesto , García Ignacio , Villalpando-Arteaga Vinicio , Torres Jesus 
Published: June 2021

Abstract
Physalis ixocarpa Brot. is a native species that is consumed in many localities of the Cienega-Chapala in Mexico's Michoacan state. These fruits are cultivated and collected into traditional maize crops. The fruits are similar to P. Philadelphica, but the differences are in the fruit size and organoleptic properties (flavor, sweetness). According to antecedents of domestication that this zone represents in Mexico, is possible that P. ixocarpa shows incipient differentiation signals in genetic structure and metabolomic fingerprinting. Our objective was find evidences of genetic and metabolomic differentiation among populations of P. ixocarpa in the Cienega-Chapala. We used the sequencing of the chloroplast intergenic sequences psbJ – petA and trnL – rpL32, and the metabolomic fingerprinting by GC-MS. The results showed that exist genetic differentiation (FST) and signatures of selection (Fu's Fs' neutrality test) among populations. Moreover the metabolomic fingerprinting showed differences among populations and an increase of aldehydes, aromatic aldehydes, ester, and alcohols related with organoleptic properties of P. ixocarpa. We conclude that P. ixocarpa is an important genetic resource with signatures of differentiation in the Cienega-Chapala, Michoacan state, Mexico that eventually could be related with domestication signatures.
In Vivo Multimodal Retinal Imaging Correlates With Granular-specific Changes in the Organelles of Retinal Pigment Epithelium of a Murine Model of Stargardt Disease
Authors: Meleppat Ratheesh K. , Ronning Kaitryn E. , Karlen Sarah J. , Burns Marie E. , Pugh Edward N. , Zawadzki Robert J. 
Published: June 2021

Abstract
Melanosomes, lipofuscin, and melanolipofuscin are the three principal types of granular pigmented organelles found in the retinal pigment epithelium (RPE) cells. Changes in the density of melanosomes and lipofuscin granules in RPE cells are considered hallmarks of various retinal diseases, including Stargardt disease and age-related macular degeneration (AMD). Herein, we report the potential of an in vivo multimodal imaging technique based on directional back-scattering and short-wavelength fundus autofluorescence (SW-FAF) to study the disease-related changes in the density of melanosomes and lipofuscin granules in RPE cells. Changes in the concentration of these granules in Abca4-/- mice (a model of Stargardt disease) relative to age-matched wild-type (WT) controls were investigated. Directional optical coherence tomography (dOCT) was used to assess the melanosome density in vivo, whereas the AF images and emission spectra acquired with a spectrometer-integrated scanning laser ophthalmoscope (SLO) were used to characterize the lipofuscin and melanolipofuscin granules in the same RPE region. Subcellular-resolution ex vivo imaging using confocal fluorescence microscopy and electron microscopy was performed on the same tissue region to visualize and quantify melanosomes, lipofuscin, and melanolipofuscin granules. Comparisons between in vivo and ex vivo results confirmed an increased concentration of lipofuscin granules and decreased number of melanosomes in the RPE of Abca4-/- mice and provided an explanation for the differences in fluorescence and directionality of RPE scattering observed in vivo in the two mouse strains.
Aqueous Mechano-Bactericidal Action of Acicular Aragonite Crystals
Authors: Negishi Nobuaki , Inaba Tomohiro , Miyazaki Yukari , Ishii Genki , Yingnan Yang , Koura Setsuko 
Published: June 2021

Abstract
Nanoneedle structures on dragonfly and cicada wing surfaces or black silicon nanoneedles demonstrate antibacterial phenomena, namely mechano-bactericidal action. These air-exposed, mechano-bactericidal surfaces serve to destroy adherent bacteria, but their bactericidal action in the water is no precedent to report. Calcium carbonate easily accumulates on surfaces during long-term exposure to hard water. We expect that aragonite nanoneedles, in particular, which grow on TiO2 during the photocatalytic treatment of calcium-rich groundwater, exhibit mechano-bactericidal action against bacteria in water. Here, we show that aragonite nanoneedles are grown on TiO2 ceramics from the calcium bicarbonate in mineral water exhibit mechano-bactericidal action against E. coli K-12 in water. Unmodified, calcite-modified as references and aragonite-modified TiO2 ceramics were exposed to water containing E. coli K-12 (in a petri dish), and their bactericidal action over time was investigated under static and agitated conditions. The surfaces of the materials were observed by scanning electron microscopy, and the live/dead bacterial cells were observed by confocal laser scanning microscopy. Further, the synergistic bactericidal performance achieved by mechano-bactericidal action and photocatalysis was demonstrated. Aragonite itself has a high biological affinity for the human body different from the other whisker-sharpen nano-materials, therefore, the mechano-bactericidal action of acicular aragonite in water is expected to inform the development of safe water purification systems for use in developing countries.