bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternariol exerts embryotoxic and immunotoxic effects on mouse blastocysts through ROS-mediated apoptotic processes
Authors: Huang Chien-Hsun , Wang Fu-Ting , Chan Wen-Hsiung 
Published: May 2021

Abstract
Alternariol (AOH), a mycotoxin belonging to the genus Alternaria, has been shown to induce cytotoxicity, including apoptosis and cell cycle arrest, in several mammalian cell types. However, its effects on early-stage embryonic development require further investigation. Here, we have shown that AOH exerts embryotoxic effects on mouse blastocyst-stage embryos and long-term adverse effects on immunity in one-day-old newborn mice of the next generation. Significant apoptosis and decrease in total cell number, predominantly through loss of inner cell mass (ICM), and to a minor extent, trophectoderm (TE) cells, were observed in AOH-treated blastocysts. Moreover, AOH exerted detrimental effects on pre- and post-implantation embryo development potential and induced a decrease in fetal weight in in vitro development and embryo transfer assays. Injection of pregnant mice with AOH (1, 3 and 5 mg/kg body weight/day) for 4 days resulted in apoptosis of blastocyst-stage embryos and injurious effects on embryonic development from the zygote to blastocyst stage or embryo degradation and a further decrease in fetal weight. Furthermore, AOH exerted a long-term impact on the next generation, triggering a significant increase in total oxidative stress content and expression of genes encoding antioxidant proteins. Lower expression of CXCL1, IL-1β and IL-8 related to innate immunity was detected in liver tissue extracts obtained from one-day-old newborns of AOH-injected pregnant mice (5 mg/kg body weight/day) relative to their non-treated counterparts. In addition, ROS served as an upstream regulator of AOH-triggered apoptotic processes and impairment of embryonic development. Our collective results highlight the potential of AOH as an embryotoxic and immunotoxic risk factor during embryo and infant development stages in mice.
Sequencing and Functional Annotation of mRNAs and lncRNAs from Tea (Camellia sinensis) Leaves During Infection by the Fungal Pathogen Lasiodiplodia theobromae
Authors: Li Dongxue , Jiang Silong , Wen Xiaodong , Song Xingchen , Yang Yuanyou , Wang Yu , Huang Honglin , Wang Delu , Chen Zhuo 
Published: May 2021

Due to the absence of effective control measures, tea leaf spot, caused by Lasiodiplodia theobromae, can seriously reduce the production and quality of tea leaves. Analysis of the relationship between messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) of tea could help to prevent and control the disease. In this current study, high-performance sequencing of mRNA and lncRNA from tea leaves during infection by L. theobromae was conducted using the Illumina HiSeq 4000 platform. Of the differentially expressed mRNAs, 2,503 or 5,278 were significantly up- or down regulated, respectively, in challenged leaves relative to unchallenged leaves. Differentially expressed lncRNAs were also analyzed at the level of genes for the above two treatments. The numbers of significantly up- or downregulated lncRNAs were 3,403 or 1,477, respectively. Functional analysis of mRNA revealed that L. theobromae challenge can induce the upregulation of the genes of seven transmembrane MLO family protein -3, -6, -11, major allergen Pru ar 1, and so on. In total, 176 differentially expressed lncRNAs occurred in response to L. theobromae challenge as a result of cis regulation, with 146 differentially expressed mRNAs. At the biological process of defense response, the glycosyl hydrolase 9A1 gene was cis regulated by the differentially expressed lncRNA. The expression profiling and association studies of the tea host infected by L. theobromae will provide a resource for future research into host–pathogen interactions and disease resistance. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
A brand new era of cancer immunotherapy: breakthroughs and challenges
Authors: Bai Ri-Lan , Chen Nai-Fei , Li Ling-Yu , Cui Jiu-Wei 
Published: May 2021

Abstract
Immunotherapy has opened a new era in cancer treatment. Drugs represented by immune checkpoint inhibitors have led to important breakthroughs in the treatment of various solid tumors, greatly improving the survival rate of cancer patients. Many types of immunotherapeutic drugs have become widely available; however, their efficacy is variable, and relatively few patients with advanced cancer experience life-altering durable survival, reflecting the complex and highly regulated nature of the immune system. The research field of cancer immunotherapy (CIT) still faces many challenges in pursuing the broader social goal of “curing cancer.” Increasing attention has been paid to strengthening the understanding of the molecular or cellular drivers of resistance to immunotherapy, actively exploring more effective therapeutic targets, and developing combination therapy strategies. Here, we review the key challenges that have emerged in the era of CIT and the possible solutions or development directions to overcome these difficulties, providing relevant references for basic research and the development of modified clinical treatment regimens.
Head-to-head comparison of the test performance of self-administered qualitative vs. laboratory-based quantitative fecal immunochemical tests in detecting colorectal neoplasm
Authors: Lu Ming , Zhang Yu-Han , Lu Bin , Cai Jie , Liu Cheng-Cheng , Chen Hong-Da , Dai Min 
Published: May 2021

Abstract

Background:
Fecal immunochemical tests (FITs) are the most widely used non-invasive tests in colorectal cancer (CRC) screening. However, evidence about the direct comparison of the test performance of the self-administered qualitative a laboratory-based quantitative FITs in a CRC screening setting is sparse.

Methods:
Based on a CRC screening trial (TARGET-C), we included 3144 pre-colonoscopy fecal samples, including 24 CRCs, 230 advanced adenomas, 622 non-advanced adenomas, and 2268 participants without significant findings at colonoscopy. Three self-administered qualitative FITs (Pupu tube) with positivity thresholds of 8.0, 14.4, or 20.8 μg hemoglobin (Hb)/g preset by the manufacturer and one laboratory-based quantitative FIT (OC-Sensor) with a positivity threshold of 20 μg Hb/g recommended by the manufacturer were tested by trained staff in the central laboratory. The diagnostic performance of the FITs for detecting colorectal neoplasms was compared in the different scenarios using the preset and adjusted thresholds (for the quantitative FIT).

Results:
At the thresholds preset by the manufacturers, apart from the qualitative FIT-3, significantly higher sensitivities for detecting advanced adenoma were observed for the qualitative FIT-1 (33.9% [95% CI: 28.7–39.4%]) and qualitative FIT-2 (22.2% [95% CI: 17.7–27.2%]) compared to the quantitative FIT (11.7% [95% CI: 8.4–15.8%]), while at a cost of significantly lower specificities. However, such difference was not observed for detecting CRC. For scenarios of adjusting the positivity thresholds of the quantitative FIT to yield comparable specificity or comparable positivity rate to the three qualitative FITs accordingly, there were no significant differences in terms of sensitivity, specificity, positive/negative predictive values and positive/negative likelihood ratios for detecting CRC or advanced adenoma between the two types of FITs, which was further evidenced in ROC analysis.

Conclusions:
Although the self-administered qualitative and the laboratory-based quantitative FITs had varied test performance at the positivity thresholds preset by the manufacturer, such heterogeneity could be overcome by adjusting thresholds to yield comparable specificities or positivity rates. Future CRC screening programs should select appropriate types of FITs and define the thresholds based on the targeted specificities and manageable positivity rates.
“Go”, “No Go,” or “Where to Go”; does microbiota dictate T cell exhaustion, programming, and HIV persistence?
Authors: Shukla Sudhanshu , Kumari Sangeeta , Bal Saswat K. , Monaco Daniela C. , Ribeiro Susan Pereira , Sekaly Rafick-Pierre , Sharma Ashish Arunkumar 
Published: May 2021

Purpose of review
People living with HIV who fail to fully reconstitute CD4+T cells after combination antiretroviral therapy therapy (i.e. immune nonresponders or INRs) have higher frequencies of exhausted T cells are enriched in a small pool of memory T cells where HIV persists and have an abundance of plasma metabolites of bacterial and host origins. Here, we review the current understanding of critical features of T cell exhaustion associated with HIV persistence; we propose to develop novel strategies to reinvigorate the effector function of exhausted T cells with the aim of purging the HIV reservoir.

Recent findings
We and others have recently reported the role of microbiota and metabolites in regulating T cell homeostasis, effector function, and senescence. We have observed that bacteria of the Firmicute phyla (specifically members of the genus Lactobacilli), associated metabolites (β-hydroxybutyrate family), and bile acids can promote regulatory T cell differentiation in INRs with a senescent peripheral blood gene expression profile.

Summary
The cross-talk between immune cells and gut microbes at the intestinal mucosa (a major effector site of the mucosal immune response), regulates the priming, proliferation, and differentiation of local and distant immune responses. This cross-talk via the production of major metabolite families (like serum amyloid A, polysaccharide A, and aryl hydrocarbon receptor ligands) plays a key role in maintaining immune homeostasis. HIV infection/persistence leads to gut dysbiosis/microbial translocation, resulting in the local and systemic dissemination of microbes. The ensuing increase in immune cell-microbiome (including pathogens) interaction promotes heightened inflammatory responses and is implicated in regulating innate/adaptive immune effector differentiation cascades that drive HIV persistence. The exact role of the microbiota and associated metabolites in regulating T cell- mediated effector functions that can restrict HIV persistence continue to be the subject of on-going studies and are reviewed here.
Guided Self-rehabilitation Contracts Combined With AbobotulinumtoxinA in Adults With Spastic Paresis
Authors: Gracies Jean-Michel , Francisco Gerard E. , Jech Robert , Khatkova Svetlana , Rios Carl D. , Maisonobe Pascal 
Published: May 2021

Background and Purpose:
Guided self-rehabilitation contracts (GSCs) are a diary-based rehabilitation strategy, wherein specific muscles are identified for prescription of high-load, home self-stretching techniques. We assessed the effect of GSCs combined with simultaneous upper limb (UL) and lower limb (LL) abobotulinumtoxinA injections on composite active range of motion (CXA) in adults with chronic spastic paresis.

Methods:
This was an international, prospective, single-arm, open-label study (ENGAGE, NCT02969356). Personalized GSCs were monitored by phone every other week, alongside 2 consecutive abobotulinumtoxinA injections (1500 U) across UL and LL, over 6 to 9 months. Primary outcomes were responder rates (CXA improvement ≥35° [UL] or ≥5° [LL]) at week 6 cycle 2. Secondary outcomes were active function (UL: Modified Frenchay Scale [MFS]; LL: 10-m barefoot maximal walking speed [WS]) and quality of life (12-item Short Form Health Survey, SF-12).

Results:
Of the 153 treated participants, 136 had primary endpoint data; 72.1% (95% confidence interval [CI], 64.0-78.9) were responders. Mean (SD) CXA changes from baseline to last study visit were +49.3° (63.4) for UL and +20.1° (27.6) for LL. Mean (95% CI) changes from baseline to week 12 cycle 2 were +0.55 (0.43-0.66) in MFS, +0.12 m/s (0.09-0.15) for WS, and +4.0 (2.8-5.2) for SF-12 physical scores. In the safety population (n = 157), 49.7% of participants reported treatment-emergent adverse events (AEs); 12.1% reported 25 serious AEs.

Discussion and Conclusions:
GSC combined with simultaneous UL and LL abobotulinumtoxinA injections led to improvements in CXA and function in both limbs, and quality-of-life physical scores. These results suggest the beneficial effect of combined GSC and abobotulinumtoxinA therapy in the management of spastic paresis.

Video Abstract available for more insight from the authors (see the Supplementary Video, available at: http://links.lww.com/JNPT/A346).
Predisposition of COVID-19 patients to secondary infections: set in stone or subject to change?
Authors: Sopirala Madhuri M. 
Published: May 2021

Purpose of review
There likely are several predisposing factors to secondary infections in patients with Coronavirus disease 2019 (COVID-19), some of which may be preventable. The aim of this review is to explore the literature, summarize potential predisposing factors to secondary infections and their incidence. It also summarizes a variety of healthcare scenarios in which different kinds of secondary infections occur.

Recent findings
Apart from immune dysregulation, severe resource limitations in healthcare settings have made COVID-19 units conducive to a variety of secondary infections. Long-term effect of excess antibiotic use in COVID-19 patients is yet to be studied. Very few studies have assessed secondary infections as the primary outcome measure making it difficult to know the true incidence. Mortality attributable to secondary infections in COVID-19 patients is also unclear.

Summary
Incidence of secondary infections in COVID-19 patients is likely higher than what is reported in the literature. Well designed studies are needed to understand the incidence and impact of secondary infections in this patient population. Many of these may be preventable especially now, as personal protective equipment and other healthcare resources are recovering. Infection prevention and control (IPC) and antimicrobial stewardship programmes (ASP) must reassess current situation to correct any breaches that could potentially cause more harm in these already vulnerable patients as we brace for a future surge with another pandemic wave.
Risk Factors for Intraoperative Seizures in Glioma Surgery: Electrocorticography Matters
Authors: Lettieri Christian , Ius Tamara , Verriello Lorenzo , Budai Riccardo , Isola Miriam , Valente Mariarosaria , Skrap Miran , Gigli Gian Luigi , Pauletto Giada 
Published: May 2021

Purpose:
Few and contradictory data are available regarding intraoperative seizures during surgery for low-grade gliomas. Aim of this study was to evaluate possible risk factors for the occurrence of IOS.

Methods:
The authors performed a retrospective analysis of 155 patients affected by low-grade gliomas and tumor-related epilepsy, who underwent surgery in our Department, between 2007 and 2018. A statistical analysis was performed by means of univariate and multivariate regression to evaluate any possible correlation between seizure occurrence and several demographic, clinical, neurophysiological, and histopathological features.

Results:
Intraoperative seizure occurred in 39 patients (25.16%) with a total of 62 seizure events recorded. Focal seizures were the prevalent seizure type: among them, 39 seizures did not show motor signs, being those with only electrographic and/or with cognitive features the most represented subtypes. Twenty-six seizures occurring during surgery were not spontaneous: direct cortical stimulation with Penfield paradigm was the most prevalent evoking factor. The univariate analysis showed that the following prognostic factors were statistically associated with the occurrence of intraoperative seizure: the awake technique (P = 0.01) and the interictal epileptiform discharges detected on the baseline electrocorticography (ECoG) (P < 0.001). After controlling for confounding factors with multivariate analysis, the awake surgery and the epileptic ECoG pattern kept statistical significance.

Conclusions:
The awake surgery procedure and the epileptic ECoG pattern are risk factors for intraoperative seizure. ECoG is mandatory to detect electrographic seizures or seizures without motor signs.
Experimental investigation to verify if excessive plastic sheeting shielding produce micro clusters of SARS-CoV-2
Authors: Ishigaki Yo , Kawauchi Yuto , Yokogawa Shinji , Saito Akira , Kitamura Hiroko , Moritake Takashi 
Published: May 2021

AbstractWe experimentally investigated indoor air ventilation using the CO2 tracer technique to verify the infection cluster of SARS-CoV-2 that erupted at an office space. Multi-placed observations revealed extremely low air change rates (0.1/h) at the site. The local infection clusters were observed several meters away from a door that is the only ventilation in the office, which suggests a negative effect of plastic sheeting shielding. The thermo-fluid simulation showed that the plastic sheet blocked the airflow and trapped the exhaled air in each partition cell. As risk suppression methods, improving air ventilation by opening windows and using fans were verified, and significant improvements (10–28/h) were observed for each partition cells.
Feasibility of an Innovative Absorbable Ventilation Tube Designed to Provide Intermediate-Term Middle Ear Ventilation
Authors: Skovlund Sandra , Cofer Shelagh , Weinreich Heather 
Published: May 2021

ABSTRACTMyringotomy with ventilation tube placement is a common surgical procedure performed in children and adults to remove fluid build-up behind the tympanic membrane. However, retention of tubes beyond achievement of therapeutic response increases risk for complications and additional intervention. This small feasibility study was conducted to demonstrate proof-of-concept of a novel bioabsorbable ventilation tube that provides the necessary duration of ventilation with absorption shortly thereafter in humans. Tubes were placed in 15 ears of 14 patients meeting indications for short or intermediate-duration of middle ear ventilation. Two independent examiners documented tube patency and tube absorption status at 3, 6 and 12 weeks or until absorption was complete. Results indicate that average ventilation time was 12 weeks (range 3 weeks to 18 months). There was no observation of blockage. These findings support the feasibility of a novel bioabsorbable ventilation tube.
Antigen-experienced CXCR5-CD19lowB cells are plasmablast precursors expanded in SLE
Authors: Szelinski Franziska , Stefanski Ana Luisa , Wiedemann Annika , Schrezenmeier Eva , Rincon-Arevalo Hector , Reiter Karin , Lettau Marie , Dang Van Duc , Fuchs Sebastian , Frei Andreas P. , Alexander Tobias , Lino Andreia C. , Dörner Thomas 
Published: May 2021

AbstractB cells play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). We analysed two independent cohorts of healthy donors and SLE patients using a combined approach of flow and mass cytometry. We have found that IgD-CD27+switched and atypical IgD-CD27-memory B cells, which are increased in SLE, represent heterogeneous populations composed each of three different subsets, such as CXCR5+CD19int, CXCR5-CD19highand CXCR5-CD19low. Here, we characterize a hitherto unknown antigen-experienced CXCR5-CD19lowB cell subsets enhanced in SLE and carrying a plasmablast (PB) phenotype enriched for switched immunoglobulins, and expressing CD38, CD95, CD71,PRDM1, XBP-1, andIRF4. CXCR5-CD19lowresemble activated B cells with a characteristically diminished B cell receptor responsiveness. CXCR5-CD19lowB cells increased with PB frequencies in SLE and upon BNT162b2 vaccination suggesting their interrelationship. Our data suggest that CXCR5-CD19lowB cells are precursors of plasmablasts, thus co-targeting this subset may have therapeutic value in SLE.
Circulating LIGHT (TNFSF14) and Interleukin-18 Levels in Sepsis-Induced Multi-Organ Injuries
Authors: Qu Hui-Qi , Snyder James , Connolly John , Glessner Joseph , Kao Charlly , Sleiman Patrick , Hakonarson Hakon 
Published: May 2021

AbstractThe novel therapeutic target cytokine LIGHT (TNFSF14) was recently shown to play a major role in COVID19-induced acute respiratory distress syndrome (ARDS). This study aims to investigate the associations of plasma LIGHT and another potentially targetable cytokine, Interleukin-18 (IL-18), with ARDS, acute hypoxic respiratory failure (AHRF) or acute kidney injury (AKI), caused by non-COVID19 viral or bacterial sepsis. A cohort of 280 subjects diagnosed with sepsis, including 91 cases with sepsis triggered by viral infections, were investigated in this cohort study. Day 0 plasma LIGHT and IL-18, as well as 59 other biomarkers (cytokines, chemokines and acute-phase reactants) were measured by sensitive bead immunoassay and associated with symptom severity. We observed significantly increased LIGHT level in both bacterial sepsis patients (P=1.80E-05) and patients with sepsis from viral infections (P=1.78E-03). In bacterial sepsis, increased LIGHT level was associated with ARDS, AKI and higher Apache III scores, findings also supported by correlations of LIGHT with other biomarkers of organ failures. IL-18 levels were highly variable across individuals, and consistently correlated with Apache III scores, mortality, and AKI, in both bacterial and viral sepsis. There was no correlation between LIGHT and IL-18. For the first time, we demonstrate independent effects of LIGHT and IL-18 in septic organ failures. The association of plasma LIGHT with AHRF suggests that targeting the pathway warrants exploration, and ongoing trials may soon elucidate whether this is beneficial. Given the large variance of plasma IL-18 among septic subjects, targeting this pathway requires a precision application.
Effective interferon (IFN)-λ treatment regimen to control lethal MERS-CoV infection in mice
Authors: Dijkman Ronald , Selvaraj Muneeswaran , Gad Hans Hendrik , Hartmann Rune , More Sunil , Perlman Stanley , Thiel Volker , Channappanavar Rudragouda 
Published: May 2021

AbstractEffective broad-spectrum antivirals are critical to prevent and control emerging human coronavirus (hCoV) infections. Despite considerable progress made towards identifying and evaluating several synthetic broad-spectrum antivirals against hCoV infections, a narrow therapeutic window has limited their success. Enhancing the endogenous interferon (IFN) and interferon-stimulated gene (ISG) response is another antiviral strategy known for decades. However, the side effects of pegylated type-I IFNs (IFN-Is) and the pro-inflammatory response detected after delayed IFN-I therapy have discouraged their clinical use. In contrast to IFN-Is, IFN-λ, a dominant IFN at the epithelial surface, is shown to be less pro-inflammatory. Consequently, we evaluated the prophylactic and therapeutic efficacy of IFN-λ in hCoV infected airway epithelial cells and mice. Human primary airway epithelial cells treated with a single dose of IFN-I (IFN-α) and IFN-λ showed similar ISG expression, whereas cells treated with two doses of IFN-λ expressed elevated levels of ISG compared to IFN-a treated cells. Similarly, mice treated with two dose IFN-λ were better protected compared to mice receiving a single dose, and a combination of prophylactic and delayed therapeutic regimens completely protected mice from lethal MERS-CoV-infection. A two dose IFN-λ regimen significantly reduced lung viral RNA and inflammatory cytokine levels with marked improvement in lung inflammation. Collectively, we identify an ideal regimen for IFN-λ use and demonstrate the protective efficacy of IFN-λ in MERS-CoV infected mice.