bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-Time Music Following in Score Sheet Images via Multi-Resolution Prediction
Authors: Henkel Florian , Widmer Gerhard
Published: November 2021

The task of real-time alignment between a music performance and the corresponding score (sheet music), also known as score following, poses a challenging multi-modal machine learning problem. Training a system that can solve this task robustly with live audio and real sheet music (i.e., scans or score images) requires precise ground truth alignments between audio and note-coordinate positions in the score sheet images. However, these kinds of annotations are difficult and costly to obtain, which is why research in this area mainly utilizes synthetic audio and sheet images to train and evaluate score following systems. In this work, we propose a method that does not solely rely on note alignments but is additionally capable of leveraging data with annotations of lower granularity, such as bar or score system alignments. This allows us to use a large collection of real-world piano performance recordings coarsely aligned to scanned score sheet images and, as a consequence, improve over current state-of-the-art approaches.
Planning for Human-Wildlife Coexistence: Conceptual Framework, Workshop Process, and a Model for Transdisciplinary Collaboration
Authors: Marchini Silvio , Ferraz Katia M. P. M. B. , Foster Vania , Reginato Thiago , Kotz Aline , Barros Yara , Zimmermann Alexandra , Macdonald David W.
Published: November 2021

Coexistence, as a concept and as a management goal and practice, has attracted increasing attention from researchers, managers and decision-makers dedicated to understanding and improving human-wildlife interactions. Although it still lacks a universally agreed definition, coexistence has increasingly been associated with a broad spectrum of human-wildlife interactions, including positive interactions, transcending a conservation focus on endangered wildlife, and involving explicitly considerations of power, equity and justice. In a growingly complex and interconnected human-dominated world, the key to turning human-wildlife interactions into large-scale coexistence is thorough planning. We present an approach for evidence-based, structured, and participatory decision-making in planning for human-wildlife coexistence. More specifically, we propose (i) a conceptual framework for describing the situation and setting the goals, (ii) a process for examining the causes of the situation and creating a theory of change, and (iii) a model for transdisciplinary research and collaboration integrating researchers, decision-makers and residents along with the interests of wildlife. To illustrate the approach, we report on the workshop considering the Jaguars of Iguaçu, a conservation project whose strategy includes the improvement of the relationship between ranchers and jaguars outside Iguaçu National Park, Brazil.
Exploring Post COVID-19 Outbreak Intradaily Mobility Pattern Change in College Students: A GPS-Focused Smartphone Sensing Study
Authors: Wu Congyu , Fritz Hagen , Miller Melissa , Craddock Cameron , Kinney Kerry , Castelli Darla , Schnyer David
Published: November 2021

With the outbreak of the COVID-19 pandemic in 2020, most colleges and universities move to restrict campus activities, reduce indoor gatherings and move instruction online. These changes required that students adapt and alter their daily routines accordingly. To investigate patterns associated with these behavioral changes, we collected smartphone sensing data using the Beiwe platform from two groups of undergraduate students at a major North American university, one from January to March of 2020 (74 participants), the other from May to August (52 participants), to observe the differences in students' daily life patterns before and after the start of the pandemic. In this paper, we focus on the mobility patterns evidenced by GPS signal tracking from the students' smartphones and report findings using several analytical methods including principal component analysis, circadian rhythm analysis, and predictive modeling of perceived sadness levels using mobility-based digital metrics. Our findings suggest that compared to the pre-COVID group, students in the mid-COVID group generally 1) registered a greater amount of midday movement than movement in the morning (8–10 a.m.) and in the evening (7–9 p.m.), as opposed to the other way around; 2) exhibited significantly less intradaily variability in their daily movement; 3) visited less places and stayed at home more everyday, and; 4) had a significant lower correlation between their mobility patterns and negative mood.
14,000-year Carbon Accumulation Dynamics in a Siberian Lake Reveal Catchment and Lake Productivity Changes
Authors: Hughes-Allen Lara , Bouchard Frédéric , Hatté Christine , Meyer Hanno , Pestryakova Lyudmila A. , Diekmann Bernhard , Subetto Dmitry A. , Biskaborn Boris K.
Published: November 2021

A multi-proxy paleolimnological analysis of a sediment core sequence from Lake Malaya Chabyda in Central Yakutia (Eastern Siberia, Russia) was conducted to investigate changes in lake processes, including lake development, sediment and organic carbon accumulation, and changes in primary productivity, within the context of Late Pleistocene and Holocene climate change. Age-depth modeling with 14C indicates that the maximum age of the sediment core is ∼14 cal kBP. Three distinct sedimentary units were identified within the sediment core. Sedimentological and biogeochemical properties in the deepest section of the core (663–584 cm; 14.1–12.3 cal kBP) suggests a lake environment mostly influenced by terrestrial vegetation, where organic carbon accumulation might have been relatively low (average ∼100 g OC m−2 a−1), although much higher than the global modern average. The middle section of the core (584–376 cm; 12.3–9.0 cal kBP) is characterized by higher primary productivity in the lake, much higher sedimentation, and a remarkable increase in OC delivery (average ∼300 g OC m−2 a−1). Conditions in the upper section of the core (<376 cm; < 9.0 cal kBP) suggest high primary productivity in the lake and high OC accumulation rates (average ∼200 g OC m−2 a−1), with stable environmental conditions. The transition from organic-poor and mostly terrestrial vegetation inputs (TOC/TNatomic ratios ∼20) to conditions dominated by aquatic primary productivity (TOC/TNatomic ratios <15) occurs at around 12.3 cal kBP. This resulted in an increase in the sedimentation rate of OC within the lake, illustrated by higher sedimentation rates and very high total OC concentrations (>30%) measured in the upper section of the core. Compact lake morphology and high sedimentation rates likely resulted in this lake acting as a significant OC sink since the Pleistocene-Holocene transition. Sediment accumulation rates declined after ∼8 cal k BP, however total OC concentrations were still notably high. TOC/TNatomic and isotopic data (δ13C) confirm the transition from terrestrial-influenced to aquatic-dominated conditions during the Early Holocene. Since the mid-Holocene, there was likely higher photosynthetic uptake of CO2 by algae, as suggested by heavier (isotopically enriched) δ13C values (>−25‰).
Transient Effects in Atmosphere and Ionosphere Preceding the 2015 M7.8 and M7.3 Gorkha–Nepal Earthquakes
Authors: Ouzounov Dimitar , Pulinets Sergey , Davidenko Dmitry , Rozhnoi Alexandr , Solovieva Maria , Fedun Viktor , Dwivedi B. N. , Rybin Anatoly , Kafatos Menas , Taylor Patrick
Published: November 2021

We analyze retrospectively/prospectively the transient variations of six different physical parameters in the atmosphere/ionosphere during the M7.8 and M7.3 earthquakes in Nepal, namely: 1) outgoing longwave radiation (OLR) at the top of the atmosphere (TOA); 2) GPS/TEC; 3) the very-low-frequency (VLF/LF) signals at the receiving stations in Bishkek (Kyrgyzstan) and Varanasi (India); 4) Radon observations; 5) Atmospheric chemical potential from assimilation models; and; 6) Air Temperature from NOAA ground stations. We found that in mid-March 2015, there was a rapid increase in the radiation from the atmosphere observed by satellites. This anomaly was located close to the future M7.8 epicenter and reached a maximum on April 21–22. The GPS/TEC data analysis indicated an increase and variation in electron density, reaching a maximum value during April 22–24. A strong negative TEC anomaly in the crest of EIA (Equatorial Ionospheric Anomaly) occurred on April 21, and a strong positive anomaly was recorded on April 24, 2015. The behavior of VLF-LF waves along NWC-Bishkek and JJY-Varanasi paths has shown abnormal behavior during April 21–23, several days before the first, stronger earthquake. Our continuous satellite OLR analysis revealed this new strong anomaly on May 3, which was why we anticipated another major event in the area. On May 12, 2015, an M7.3 earthquake occurred. Our results show coherence between the appearance of these pre-earthquake transient’s effects in the atmosphere and ionosphere (with a short time-lag, from hours up to a few days) and the occurrence of the 2015 M7.8 and M7.3 events. The spatial characteristics of the pre-earthquake anomalies were associated with a large area but inside the preparation region estimated by Dobrovolsky-Bowman. The pre-earthquake nature of the signals in the atmosphere and ionosphere was revealed by simultaneous analysis of satellite, GPS/TEC, and VLF/LF and suggest that they follow a general temporal-spatial evolution pattern that has been seen in other large earthquakes worldwide.
Effects of School Closures Resulting From COVID-19 in Autistic and Neurotypical Children
Authors: Genova Helen M. , Arora Aditi , Botticello Amanda L.
Published: November 2021

The purpose of this study was to assess differences in negative consequences resulting from pandemic-related school closures between autistic and neurotypical children. We predicted that more negative consequences overall would be reported for children with autism compared to neurotypical children. We also expected to observe differences in the types of stressors reported between these two groups, with disruptions to daily routines more commonly reported for children with autism and stress due to social isolation more commonly reported for neurotypical children. Participants were parents of school-aged children, ages of 4–15 years old, who responded to an online survey (N = 250). Parental perspectives were collected using the Covid-19 Adolescent Symptom and Psychological Experience Questionnaire (CASPE). Parents in the autism group were additionally asked to respond to a survey about autism-specific stressors which may have increased during the pandemic, such as behavioral concerns, therapy disruptions, and hygiene issues. The majority of the respondents (65%) were parents of children with autism and 35% were parents of neurotypical children. Parents of autistic children were more likely to report that their child was negatively affected by routine changes, whereas parents of neurotypical children were more likely to report that their child was affected by social isolation. Overall, parents of children with autism were more than three times as likely to report negative changes in their child compared to parents of neurotypical children. When asked about autism-specific stressors, parents of autistic children reported concerns related to hygiene, behavioral regression, therapy disruption, meltdowns, and returning to school. The effects of the COVID-19 pandemic and prolonged school closures have disrupted the lives of children. Our results indicate that children with autism are at greater risk for negative outcomes due to emergency-related school disruptions. These findings have implications for educational planning for this vulnerable population for future public health crises.
Decreased DNA Repair Ability: A Mechanism for Low Early Embryonic Development Potential of Oocytes From Overweight Patients After Fertilization in IVF Cycles
Authors: Li Hui , Wang Huan , Zhu Jing , Xu Jianmin , Jiang Yuqing , Chen Wenhui , Sun Yingpu , Yang Qingling
Published: November 2021

Background

Whether female BMI impacts the DNA repair ability in the oocytes after fertilization has not been investigated. The aim of this study is to assess the early embryo quality and reproductive outcomes of oocytes from overweight women when fertilized with sperm with varying degrees of DNA fragmentation.

Methods

A total number of 1,612 patients undergoing fresh autologous in vitro fertilization (IVF) cycles was included. These patients were divided into two groups according to maternal body mass index (BMI): normal weight group (18.5–24.9 kg/m2; n=1187; 73.64%) and overweight group (≥25 kg/m2; n=425; 26.36%). Each group was then subdivided into two groups by sperm DNA fragmentation index (DFI): low fragmentation group (<20% DFI, LF) and high fragmentation group (≥20% DFI, HF). Laboratory and clinical outcomes were compared between subgroups.

Results

For the normal-weight group, there was no statistical significance in embryo quality and reproductive outcomes between the LF and HF groups. But in the overweight group, significantly lower fertilization rate (LF: 64%; HF: 59%; p=0.011), blastocyst development rate (LF: 57%; HF: 44%; p=0.001), as well as high-quality blastocyst rate (LF: 32%; HF: 22%; p=0.034) were found in the HF group, despite the similar pregnancy rates (LF: 56%; HF: 60%; p=0.630).

Conclusions

Decreased DNA repair activity in oocytes may be a possible mechanism for the low early development potential of embryos from overweight patients in in vitro fertilization cycles.
Prediction of Treatment Response According to ASAS-EULAR Management Recommendations in 1 Year for Hip Involvement in Axial Spondyloarthritis Based on MRI and Clinical Indicators
Authors: Xie Zhuoyao , Lu Zixiao , Chen Hao , Ye Qiang , Guo Chang , Zheng Kai , Li Xin , Xie Qiuxia , Hu Shaoyong , Zhou Quan , Zhao Yinghua
Published: November 2021

Background

To predict the treatment response for axial spondyloarthritis (axSpA) with hip involvement in 1 year based on MRI and clinical indicators.

Methods

A total of 77 axSpA patients with hip involvement (60 males; median age, 25 years; interquartile, 22–31 years old) were treated with a drug recommended by the Assessment of SpondyloArthritis international Society and the European League Against Rheumatism (ASAS-EULAR) management. They were prospectively enrolled according to Assessment in SpondyloArthritis international Society (ASAS) criteria. Clinical indicators, including age, gender, disease duration, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were collected at baseline and in 3 months to 1-year follow-up. Treatment response was evaluated according to ASAS response criteria. MRI indicators consisting of bone marrow edema (BME) in acetabulum and femoral head, hip effusion, fat deposition, thickened synovium, bone erosion, bone proliferation, muscle involvement, enthesitis and bony ankylosis were assessed at baseline. Spearman’s correlation analysis was utilized for indicator selection. The selected clinical and MRI indicators were integrated with previous clinical knowledge to develop multivariable logistic regression models. Receiver operator characteristic curve and area under the curve (AUC) were used to assess the performance of the constructed models.

Results

The model combining MR indicators comprising hip effusion, BME in acetabulum and femoral head and clinical indicators consisting of disease duration, ESR and CRP yielded AUC values of 0.811 and 0.753 for the training and validation cohorts, respectively.

Conclusion

The model combining MRI and clinical indicators could predict treatment response for axSpA with hip involvement in 1 year.
Obesogens: How They Are Identified and Molecular Mechanisms Underlying Their Action
Authors: Mohajer Nicole , Du Chrislyn Y. , Checkcinco Christian , Blumberg Bruce
Published: November 2021

Adult and childhood obesity have reached pandemic level proportions. The idea that caloric excess and insufficient levels of physical activity leads to obesity is a commonly accepted answer for unwanted weight gain. This paradigm offers an inconclusive explanation as the world continually moves towards an unhealthier and heavier existence irrespective of energy balance. Endocrine disrupting chemicals (EDCs) are chemicals that resemble natural hormones and disrupt endocrine function by interfering with the body’s endogenous hormones. A subset of EDCs called obesogens have been found to cause metabolic disruptions such as increased fat storage, in vivo. Obesogens act on the metabolic system through multiple avenues and have been found to affect the homeostasis of a variety of systems such as the gut microbiome and adipose tissue functioning. Obesogenic compounds have been shown to cause metabolic disturbances later in life that can even pass into multiple future generations, post exposure. The rising rates of obesity and related metabolic disease are demanding increasing attention on chemical screening efforts and worldwide preventative strategies to keep the public and future generations safe. This review addresses the most current findings on known obesogens and their effects on the metabolic system, the mechanisms of action through which they act upon, and the screening efforts through which they were identified with. The interplay between obesogens, brown adipose tissue, and the gut microbiome are major topics that will be covered.
Familial Translocation t(2;4) (q37.3;p16.3), Resulting in a Partial Trisomy of 2q (or 4p) and a Partial Monosomy of 4p (or 2q), Causes Dysplasia
Authors: Wang Jian , Zhou Shiyuan , He Fei , Zhang Xuelian , Lu Jianqi , Zhang Jian , Zhang Feng , Xu Xiangmin , Yang Fang , Xiong Fu
Published: November 2021

Background: Wolf-Hirschhorn syndrome, a well-known contiguous microdeletion syndrome, is caused by deletions on chromosome 4p. While the clinical symptoms and the critical region for this disorder have been identified based on genotype-phenotype correlations, duplications in this region have been infrequently reported.

Conclusion: Our case report shows that both deletions and duplications of the Wolf-Hirshhorn critical region cause intellectual disability/developmental delay and multiple congenital anomalies.
DCET1 Controls Male Sterility Through Callose Regulation, Exine Formation, and Tapetal Programmed Cell Death in Rice
Authors: Khan Riaz Muhammad , Yu Ping , Sun Lianping , Abbas Adil , Shah Liaqat , Xiang Xiaojiao , Wang Dongfei , Sohail Amir , Zhang Yingxin , Liu Qunen , Cheng Shihua , Cao Liyong
Published: November 2021

In angiosperms, anther development comprises of various complex and interrelated biological processes, critically needed for pollen viability. The transitory callose layer serves to separate the meiocytes. It helps in primexine formation, while the timely degradation of tapetal cells is essential for the timely callose wall dissolution and pollen wall formation by providing nutrients for pollen growth. In rice, many genes have been reported and functionally characterized that are involved in callose regulation and pollen wall patterning, including timely programmed cell death (PCD) of the tapetum, but the mechanism of pollen development largely remains ambiguous. We identified and functionally characterized a rice mutant dcet1, having a complete male-sterile phenotype caused by defects in anther callose wall, exine patterning, and tapetal PCD. DCET1 belongs to the RNA recognition motif (RRM)-containing family also called as the ribonucleoprotein (RNP) domain or RNA-binding domain (RBD) protein, having single-nucleotide polymorphism (SNP) substitution from G (threonine-192) to A (isoleucine-192) located at the fifth exon of LOC_Os08g02330, was responsible for the male sterile phenotype in mutant dcet1. Our cytological analysis suggested that DCET1 regulates callose biosynthesis and degradation, pollen exine formation by affecting exine wall patterning, including abnormal nexine, collapsed bacula, and irregular tectum, and timely PCD by delaying the tapetal cell degeneration. As a result, the microspore of dcet1 was swollen and abnormally bursted and even collapsed within the anther locule characterizing complete male sterility. GUS and qRT-PCR analysis indicated that DCET1 is specifically expressed in the anther till the developmental stage 9, consistent with the observed phenotype. The characterization of DCET1 in callose regulation, pollen wall patterning, and tapetal cell PCD strengthens our knowledge for knowing the regulatory pathways involved in rice male reproductive development and has future prospects in hybrid rice breeding.
Activation of Intracellular Complement in Lungs of Patients With Severe COVID-19 Disease Decreases T-Cell Activity in the Lungs
Authors: Howell Mark C. , Green Ryan , McGill Andrew R. , Kahlil Roukiah M. , Dutta Rinku , Mohapatra Shyam S. , Mohapatra Subhra
Published: November 2021

A novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), arose late in 2019, with disease pathology ranging from asymptomatic to severe respiratory distress with multi-organ failure requiring mechanical ventilator support. It has been found that SARS-CoV-2 infection drives intracellular complement activation in lung cells that tracks with disease severity. However, the cellular and molecular mechanisms responsible remain unclear. To shed light on the potential mechanisms, we examined publicly available RNA-Sequencing data using CIBERSORTx and conducted a Ingenuity Pathway Analysis to address this knowledge gap. In complement to these findings, we used bioinformatics tools to analyze publicly available RNA sequencing data and found that upregulation of complement may be leading to a downregulation of T-cell activity in lungs of severe COVID-19 patients. Thus, targeting treatments aimed at the modulation of classical complement and T-cell activity may help alleviate the proinflammatory effects of COVID-19, reduce lung pathology, and increase the survival of COVID-19 patients.
High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids
Authors: Silva Carolina S. , Sundling Christopher , Folkesson Elin , Fröberg Gabrielle , Nobrega Claudia , Canto-Gomes João , Chambers Benedict J. , Lakshmikanth Tadepally , Brodin Petter , Bruchfeld Judith , Nigou Jérôme , Correia-Neves Margarida , Källenius Gunilla
Published: November 2021

Upon infection withMycobacterium tuberculosis(Mtb) the host immune response might clear the bacteria, control its growth leading to latent tuberculosis (LTB), or fail to control its growth resulting in active TB (ATB). There is however no clear understanding of the features underlying a more or less effective response. Mtb glycolipids are abundant in the bacterial cell envelope and modulate the immune response to Mtb, but the patterns of response to glycolipids are still underexplored. To identify the CD45+leukocyte activation landscape induced by Mtb glycolipids in peripheral blood of ATB and LTB, we performed a detailed assessment of the immune response of PBMCs to the Mtb glycolipids lipoarabinomannan (LAM) and its biosynthetic precursor phosphatidyl-inositol mannoside (PIM), and purified-protein derivate (PPD). At 24 h of stimulation, cell profiling and secretome analysis was done using mass cytometry and high-multiplex immunoassay. PIM induced a diverse cytokine response, mainly affecting antigen-presenting cells to produce both pro-inflammatory and anti-inflammatory cytokines, but not IFN-γ, contrasting with PPD that was a strong inducer of IFN-γ. The effect of PIM on the antigen-presenting cells was partly TLR2-dependent. Expansion of monocyte subsets in response to PIM or LAM was reduced primarily in LTB as compared to healthy controls, suggesting a hyporesponsive/tolerance pattern derived from Mtb infection.
Major Neutrophil-Derived Soluble Mediators Associate With Baseline Lung Pathology and Post-Treatment Recovery in Tuberculosis Patients
Authors: Muefong Caleb Nwongbouwoh , Owolabi Olumuyiwa , Donkor Simon , Charalambous Salome , Mendy Joseph , Sey Isatou C. M. , Bakuli Abhishek , Rachow Andrea , Geldmacher Christof , Sutherland Jayne S.
Published: November 2021

Background

The inflammatory response toMycobacterium tuberculosisresults in variable degrees of lung pathology during active TB (ATB) with central involvement of neutrophils. Little is known about neutrophil-derived mediators and their role in disease severity at baseline and recovery upon TB treatment initiation.

Methods

107 adults with confirmed pulmonary TB were categorised based on lung pathology at baseline and following successful therapy using chest X-ray scores (Ralph scores) and GeneXpert bacterial load (Ct values). Plasma, sputum, and antigen-stimulated levels of MMP1, MMP3, MMP8, MMP9, MPO, S100A8/9, IL8, IL10, IL12/23(p40), GM-CSF, IFNγ, and TNF were analysed using multiplex cytokine arrays.

Results

At baseline, neutrophil counts correlated with plasma levels of MMP8 (rho = 0.45, p = 2.80E−06), S100A8 (rho = 0.52, p = 3.00E−08) and GM-CSF (rho = 0.43, p = 7.90E−06). Levels of MMP8 (p = 3.00E−03), MMP1 (p = 1.40E−02), S100A8 (p = 1.80E−02) and IL12/23(p40) (p = 1.00E−02) were associated with severe lung damage, while sputum MPO levels were directly linked to lung damage (p = 1.80E−03), Mtb load (p = 2.10E−02) and lung recovery (p = 2.40E−02). Six months of TB therapy significantly decreased levels of major neutrophil-derived pro-inflammatory mediators: MMP1 (p = 4.90E−12 and p = 2.20E−07), MMP8 (p = 3.40E−14 and p = 1.30E−05) and MMP9 (p = 1.60E−04 and p = 1.50E−03) in plasma and sputum, respectively. Interestingly, following H37Rv whole cell lysate stimulation, S100A8 (p = 2.80E−02), MMP9 (p = 3.60E−02) and MPO (p = 9.10E−03) levels at month 6 were significantly higher compared to baseline. Sputum MMP1 (p = 1.50E−03), MMP3 (p = 7.58E−04), MMP9 (p = 2.60E−02) and TNF (p = 3.80E−02) levels were lower at month 6 compared to baseline in patients with good lung recovery.

Conclusion

In this study, patients with severe lung pathology at baseline and persistent lung damage after treatment were associated with higher plasma and sputum levels of major pro-inflammatory neutrophil-derived mediators. Interestingly, low sputum MPO levels were associated with severe lung damage, higher Mtb burden and low recovery. Our data suggest that therapeutic agents which target these mediators should be considered for future studies on biomarkers and host-directed therapeutic approaches against TB-related lung pathology and/or lung recovery.
Robust Antibody Levels in Both Diabetic and Non-Diabetic Individuals After BNT162b2 mRNA COVID-19 Vaccination
Authors: Ali Hamad , Alterki Abdulmohsen , Sindhu Sardar , Alahmad Barrak , Hammad Maha , Al-Sabah Salman , Alghounaim Mohammad , Jamal Mohammad H. , Aldei Ali , Mairza Mohammad J. , Husain Maitham , Deverajan Sriraman , Ahmad Rasheed , Cherian Preethi , Alkhairi Irina , Alkandari Abdullah , Abubaker Jehad , Abu-Farha Mohamed , Al-Mulla Fahd
Published: November 2021

The emergence of effective vaccines for COVID-19 has been welcomed by the world with great optimism. Given their increased susceptibility to COVID-19, the question arises whether individuals with type-2 diabetes mellitus (T2DM) and other metabolic conditions can respond effectively to the mRNA-based vaccine. We aimed to evaluate the levels of anti-SARS-CoV-2 IgG and neutralizing antibodies in people with T2DM and/or other metabolic risk factors (hypertension and obesity) compared to those without. This study included 262 people (81 diabetic and 181 non-diabetic persons) that took two doses of BNT162b2 (Pfizer–BioNTech) mRNA vaccine. Both T2DM and non-diabetic individuals had a robust response to vaccination as demonstrated by their high antibody titers. However, both SARS-CoV-2 IgG and neutralizing antibodies titers were lower in people with T2DM. The mean ( ± 1 standard deviation) levels were 154 ± 49.1 vs. 138 ± 59.4 BAU/ml for IgG and 87.1 ± 11.6 vs. 79.7 ± 19.5% for neutralizing antibodies in individuals without diabetes compared to those with T2DM, respectively. In a multiple linear regression adjusted for individual characteristics, comorbidities, previous COVID-19 infection, and duration since second vaccine dose, diabetics had 13.86 BAU/ml (95% CI: 27.08 to 0.64 BAU/ml, p=0.041) less IgG antibodies and 4.42% (95% CI: 8.53 to 0.32%, p=0.036) fewer neutralizing antibodies than non-diabetics. Hypertension and obesity did not show significant changes in antibody titers. Taken together, both type-2 diabetic and non-diabetic individuals elicited strong immune responses to SARS-CoV-2 BNT162b2 mRNA vaccine; nonetheless, lower levels were seen in people with diabetes. Continuous monitoring of the antibody levels might be a good indicator to guide personalized needs for further booster shots to maintain adaptive immunity. Nonetheless, it is important that people get their COVID-19 vaccination especially people with diabetes.
Plasma MicroRNA Signature Panel Predicts the Immune Response After Antiretroviral Therapy in HIV-Infected Patients
Authors: Lv Jun-Nan , Li Jia-Qi , Cui Ying-Bin , Ren Yuan-Yuan , Fu Ya-Jing , Jiang Yong-Jun , Shang Hong , Zhang Zi-Ning
Published: November 2021

Background

Approximately 10–40% of people with human immunodeficiency virus (HIV) infection are unable to obtain successful improvements in immune function after antiretroviral therapy (ART). These patients are at greater risk of developing non-acquired immunodeficiency syndrome (AIDS)-related conditions, with the accompanying increased morbidity and mortality. Discovering predictive biomarkers can help to identify patients with a poor immune response earlier and provide new insights into the mechanisms of this condition.

Methods

A total of 307 people with HIV were enrolled, including 110 immune non-responders (INRs) and 197 immune responders (IRs). Plasma samples were taken before ART, and quantities of plasma microRNAs (miRNAs) were determined using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Candidate biomarkers were established through four phases: discovery, training, validation, and blinded test. Binary logistic regression was used to analyze the combined predictive capacity of the identified miRNAs. The effect of one miRNA, miR-16-5p, on T cell function was assessed in vitro.

Results

Expression of five miRNAs (miR-580, miR-627, miR-138-5p, miR-16-5p, and miR-323-3p) was upregulated in the plasma of INRs compared with that in IRs. Expression of these miRNAs was negatively correlated with both CD4+ T cell counts and the increase in the proportion of CD4+ T cells after one year of ART. These five miRNAs were combined in a predictive model, which could effectively identify INRs or IRs. Furthermore, we found that miR-16-5p inhibits CD4+ T cell proliferation by regulating calcium flux.

Conclusion

We established a five-miRNA panel in plasma that accurately predicts poor immune response after ART, which could inform strategies to reduce the incidence of this phenomenon and improve the clinical management of these patients.
Predictable Roles of Peripheral IgM Memory B Cells for the Responses to Anti-PD-1 Monotherapy Against Advanced Non-Small Cell Lung Cancer
Authors: Xia Liliang , Guo Limin , Kang Jin , Yang Yi , Yao Yaxian , Xia Weimin , Sun Ruiming , Zhang Shun , Li Wenfeng , Gao Yuer , Chen Hongyan , Li Ziming , Yang Jinji , Lu Shun , Wang Ying
Published: November 2021

Tumor-infiltrating B cells and tertiary lymphoid structures have been identified to predict the responses to immune checkpoint inhibitors (ICIs) in cancer immunotherapy. Considering the feasibility of sample collection, whether peripheral B cell signatures are associated with the responses to ICI therapy remains unclear. Herein, we have defined peripheral B cell signatures in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD-1 monotherapy and investigated their associations with clinical efficacy. It was found that the percentages of B cells before the treatment (baseline) were significantly higher (P = 0.004) in responder (R, n = 17) than those in non-responder (NonR, n = 33) NSCLC patients in a discovery cohort. Moreover, the percentages of baseline IgM+ memory B cells were higher (P < 0.001) in R group than those in NonR group, and associated with a longer progression free survival (PFS) (P = 0.003). By logistic regression analysis peripheral baseline IgM+ memory B cells were identified as an independent prognostic factor (P = 0.002) for the prediction of the responses to anti-PD-1 monotherapy with the AUC value of 0.791, which was further validated in another anti-PD-1 monotherapy cohort (P = 0.011, n = 70) whereas no significance was observed in patients receiving anti-PD-L1 monotherapy (P = 0.135, n = 30). Therefore, our data suggest the roles of peripheral IgM+ memory B cells in predicting the responses to anti-PD-1 treatment in Chinese advanced NSCLC patients.
Sinomenine Hydrochloride Ameliorates Fish Foodborne Enteritis via α7nAchR-Mediated Anti-Inflammatory Effect Whilst Altering Microbiota Composition
Authors: Xie Jiayuan , Li Ming , Ye Weidong , Shan Junwei , Zhao Xuyang , Duan You , Liu Yuhang , Unger Bruno Hamish , Cheng Yingyin , Zhang Wanting , Wu Nan , Xia Xiao-Qin
Published: November 2021

Foodborne intestinal inflammation is a major health and welfare issue in aquaculture. To prevent enteritis, various additives have been incorporated into the fish diet. Considering anti-inflammatory immune regulation, an effective natural compound could potentially treat or prevent intestinal inflammation. Our previous study has revealed galantamine’s effect on soybean induced enteritis (SBMIE) and has highlighted the possible role of the cholinergic anti-inflammatory pathway in the fish gut. To further activate the intestinal cholinergic related anti-inflammatory function, α7nAchR signaling was considered. In this study, sinomenine, a typical agonist of α7nAChR in mammals, was tested to treat fish foodborne enteritis via its potential anti-inflammation effect using the zebrafish foodborne enteritis model. After sinomenine’s dietary inclusion, results suggested that there was an alleviation of intestinal inflammation at a pathological level. This outcome was demonstrated through the improved morphology of intestinal villi. At a molecular level, SN suppressed inflammatory cytokines’ expression (especially for tnf-α) and upregulated anti-inflammation-related functions (indicated by expression of il-10, il-22, and foxp3a). To systematically understand sinomenine’s intestinal effect on SBMIE, transcriptomic analysis was done on the SBMIE adult fish model. DEGs (sinomenine vs soybean meal groups) were enriched in GO terms related to the negative regulation of lymphocyte/leukocyte activation and alpha-beta T cell proliferation, as well as the regulation of lymphocyte migration. The KEGG pathways for glycolysis and insulin signaling indicated metabolic adjustments of α7nAchR mediated anti-inflammatory effect. To demonstrate the immune cells’ response, in the SBMIE larva model, inflammatory gatherings of neutrophils, macrophages, and lymphocytes caused by soybean meal could be relieved significantly with the inclusion of sinomenine. This was consistent within the sinomenine group as CD4+ or Foxp3+ lymphocytes were found with a higher proportion at the base of mucosal folds, which may suggest the Treg population. Echoing, the sinomenine group’s 16s sequencing result, there were fewer enteritis-related TM7, Sphingomonas and Shigella, but more Cetobacterium, which were related to glucose metabolism. Our findings indicate that sinomenine hydrochloride could be important in the prevention of fish foodborne enteritis at both immune and microbiota levels.
Identification, Characterization, and Transcriptional Reprogramming of Epithelial Stem Cells and Intestinal Enteroids in Simian Immunodeficiency Virus Infected Rhesus Macaques
Authors: Boby Nongthombam , Cao Xuewei , Ransom Alyssa , Pace Barcley T. , Mabee Christopher , Shroyer Monica N. , Das Arpita , Didier Peter J. , Srivastav Sudesh K. , Porter Edith , Sha Qiuying , Pahar Bapi
Published: November 2021

Epithelial cell injury and impaired epithelial regeneration are considered key features in HIV pathogenesis and contribute to HIV-induced generalized immune activation. Understanding the molecular mechanisms underlying the disrupted epithelial regeneration might provide an alternative approach for the treatment of HIV-mediated enteropathy and immune activation. We have observed a significant increased presence of α defensin5+ (HD5) Paneth cells and proliferating Ki67+ epithelial cells as well as decreased expression of E-cadherin expression in epithelial cells during SIV infection. SIV infection did not significantly influence the frequency of LGR5+ stem cells, but the frequency of HD5+ cells was significantly higher compared to uninfected controls in jejunum. Our global transcriptomics analysis of enteroids provided novel information about highly significant changes in several important pathways like metabolic, TCA cycle, and oxidative phosphorylation, where the majority of the differentially expressed genes were downregulated in enteroids grown from chronically SIV-infected macaques compared to the SIV-uninfected controls. Despite the lack of significant reduction in LGR5+ stem cell population, the dysregulation of several intestinal stem cell niche factors including Notch, mTOR, AMPK and Wnt pathways as well as persistence of inflammatory cytokines and chemokines and loss of epithelial barrier function in enteroids further supports that SIV infection impacts on epithelial cell proliferation and intestinal homeostasis.
Human Neutrophils Respond to Complement Activation and Inhibition in Microfluidic Devices
Authors: Muldur Sinan , Vadysirisack Douangsone D. , Ragunathan Sharan , Tang Yalan , Ricardo Alonso , Sayegh Camil Elie , Irimia Daniel
Published: November 2021

Complement activation is key to anti-microbial defenses by directly acting on microbes and indirectly by triggering cellular immune responses. Complement activation may also contribute to the pathogenesis of numerous inflammatory and immunological diseases. Consequently, intense research focuses on developing therapeutics that block pathology-causing complement activation while preserving anti-microbial complement activities. However, the pace of research is slowed down significantly by the limitations of current tools for evaluating complement-targeting therapeutics. Moreover, the effects of potential therapeutic agents on innate immune cells, like neutrophils, are not fully understood. Here, we employ microfluidic assays and measure chemotaxis, phagocytosis, and swarming changes in human neutrophils ex vivo in response to various complement-targeting agents. We show that whereas complement factor 5 (C5) cleavage inhibitor eculizumab blocks all neutrophil anti-microbial functions, newer compounds like the C5 cleavage inhibitor RA101295 and C5a receptor antagonist avacopan inhibit chemotaxis and swarming while preserving neutrophil phagocytosis. These results highlight the utility of microfluidic neutrophil assays in evaluating potential complement-targeting therapeutics.
Anti-SARS-CoV-2 Spike Protein RBD Antibody Levels After Receiving a Second Dose of ChAdOx1 nCov-19 (AZD1222) Vaccine in Healthcare Workers: Lack of Association With Age, Sex, Obesity, and Adverse Reactions
Authors: Lee Sang Won , Moon Ji-Yong , Lee Sun-Kyung , Lee Hyun , Moon SeolHwa , Chung Sung Jun , Yeo Yoomi , Park Tai Sun , Park Dong Won , Kim Tae-Hyung , Sohn Jang Won , Yoon Ho Joo , Kim Sang-Heon
Published: November 2021

Response to vaccines generally varies according to individual factors of the vaccinated subjects such as demographics and immune status. While there are various reports of factors associated with immunogenicity of mRNA COVID-19 vaccines, little is known about those of adenovirus vector vaccines. We conducted a prospective observational study to assess the relationships of antibody level with age, sex, body mass index (BMI), and adverse reactions (ARs) to an adenovirus vector vaccine, ChAdOx1 nCoV-19. Healthcare workers who planned to receive both the first and second injections of the ChAdOx1 nCoV-19 vaccine at Hanyang University Hospital, Seoul, Korea, were enrolled in the study. Seven days after each injection, participants were asked to complete an online adverse reaction survey. In addition, anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) antibody concentration was measured 4 weeks after the second injection. All participants (n = 447, 100%) showed serologic positivity (≥ 0.8 U/mL) 4 weeks after the second injection of ChAdOx1 nCoV-19 vaccine. Furthermore, the anti-SARS-CoV-2 S protein RBD concentration was similar among groups when stratified by age, sex, BMI, or presence and severity of AR; multivariable linear regression found no associations between antibody response to the ChAdOx1 nCoV-19 vaccine and age, BMI, sex, and vaccine-induced ARs. In conclusion, age, sex, obesity, and ARs were not associated with antibody responses after two doses of ChAdOx1 nCoV-19 vaccination.
Mitochondria in Focus: From Function to Therapeutic Strategies in Chronic Lung Diseases
Authors: Caldeira Dayene de Assis Fernandes , Weiss Daniel J. , Rocco Patricia Rieken Macêdo , Silva Pedro Leme , Cruz Fernanda Ferreira
Published: November 2021

Mitochondria are essential organelles for cell metabolism, growth, and function. Mitochondria in lung cells have important roles in regulating surfactant production, mucociliary function, mucus secretion, senescence, immunologic defense, and regeneration. Disruption in mitochondrial physiology can be the central point in several pathophysiologic pathways of chronic lung diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and asthma. In this review, we summarize how mitochondria morphology, dynamics, redox signaling, mitophagy, and interaction with the endoplasmic reticulum are involved in chronic lung diseases and highlight strategies focused on mitochondrial therapy (mito-therapy) that could be tested as a potential therapeutic target for lung diseases.
A Novel Germline Heterozygous BCL11B Variant Causing Severe Atopic Disease and Immune Dysregulation
Authors: Lu Henry Y. , Sertori Robert , Contreras Alejandra V. , Hamer Mark , Messing Melina , Del Bel Kate L. , Lopez-Rangel Elena , Chan Edmond S. , Rehmus Wingfield , Milner Joshua D. , McNagny Kelly M. , Lehman Anna , Wiest David L. , Turvey Stuart E.
Published: November 2021

B-cell lymphoma/leukemia 11B (BCL11B) is a C2H2 zinc finger transcription factor that is critically important for regulating the development and function of a variety of systems including the central nervous system, the skin, and the immune system. Germline heterozygous variants are associated with a spectrum of clinical disorders, including severe combined immunodeficiency as well as neurological, craniofacial, and dermal defects. Of these individuals, ~50% present with severe allergic disease. Here, we report the detailed clinical and laboratory workup of one of the most severe BCL11B-dependent atopic cases to date. Leveraging a zebrafish model, we were able to confirm a strong T-cell defect in the patient. Based on these data, we classify germline BCL11B-dependent atopic disease as a novel primary atopic disorder.
m6A Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Acute Myeloid Leukemia
Authors: Du Ashuai , Wu Xin , Gao Yunmei , Jiang Baili , Wang Jianlong , Zhang Pan , Zhao Qiangqiang
Published: November 2021

Recent studies have demonstrated epigenetic regulation of immune responses. Nevertheless, the underlying effect of RNA N6-methyladenosine (m6A) modifications on tumor microenvironment cell infiltration remains elusive. In this study, we thoroughly assessed m6A modification patterns of 255 myeloid leukemia specimens based on 23 m6A regulators. Consensus clustering of the 23 m6A regulators was performed to determine three distinct m6A modification patterns that were remarkably consistent with three immunophenotypes of tumors: immunorejection, immune activation, and immune inertness. Further evaluation and prognostic analysis of the m6A modification patterns of individual tumors revealed that low m6A score was characterized by increased mutational burden, immune activation, and survival rates, whereas high m6A score was characterized by poorer survival rates and the absence of effective immune infiltration. In addition, this study investigated the association between m6A regulators and antitumor immune responses and discovered higher expression of the immune regulators PD-L1, PD-L2, MRP1, and MRP2 in low m6A scores. Generally, the expression pattern of m6A regulators was remarkably associated with prognostic results and antitumor immune responses in acute myeloid leukemia and may be an underlying target and biological marker for immune therapies.
A Modular U-Net for Automated Segmentation of X-Ray Tomography Images in Composite Materials
Authors: Bertoldo João P. C. , Decencière Etienne , Ryckelynck David , Proudhon Henry
Published: November 2021

X-Ray Computed Tomography (XCT) techniques have evolved to a point that high-resolution data can be acquired so fast that classic segmentation methods are prohibitively cumbersome, demanding automated data pipelines capable of dealing with non-trivial 3D images. Meanwhile, deep learning has demonstrated success in many image processing tasks, including materials science applications, showing a promising alternative for a human-free segmentation pipeline. However, the rapidly increasing number of available architectures can be a serious drag to the wide adoption of this type of models by the end user. In this paper a modular interpretation of U-Net (Modular U-Net) is proposed with a parametrized architecture that can be easily tuned to optimize it. As an example, the model is trained to segment 3D tomography images of a three-phased glass fiber-reinforced Polyamide 66. We compare 2D and 3D versions of our model, finding that the former is slightly better than the latter. We observe that human-comparable results can be achievied even with only 13 annotated slices and using a shallow U-Net yields better results than a deeper one. As a consequence, neural networks show indeed a promising venue to automate XCT data processing pipelines needing no human, adhoc intervention.