bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of Prokaryotes on the Astomatous Ciliated Protist Kentrophoros flavus (Ciliophora, Karyorelictea) Revealed A Consistently Associated Muribaculaceae-Like Bacterium
Authors: Bi Luping , Zhang Xiaoxin , Zou Songbao , Ji Daode , Zhang Qianqian
Published: June 2022

The interactions between symbiotic bacterial consortia and their protist hosts in benthic environments have attracted increasing interest in recent years. In the present study, we investigated the diversity of potentially associated bacteria for an astomatous ciliate, Kentrophoros flavus, collected in the intertidal zone of Yantai, China. For the first time, the diversity of the associated bacteria in the species K. flavus was examined using 16S rRNA-based techniques (clone libraries and PacBio sequencing) and the fluorescence in situ hybridization (FISH) technique. The 16S rRNA-based sequencing revealed a higher diversity of associated bacteria in K. flavus than previously expected. In addition to a genus-typical thiotrophic symbiont, the “Candidatus Kentron” stain YE, we provide evidence showing the consistent existence of one Muribaculaceae-like bacterium that was secondarily abundant among the bacterial operational taxonomic units (OTUs). Fluorescence in situ hybridization (FISH) with three specific probes and double-label FISH experiments with “Candidatus Kentron” probes showed that the Muribaculaceae-like bacterium was abundant and merged with the “Candidatus Kentron” stain YE on the cell surface of the host. A phylogenetic analysis of the bacterial 16S rRNA gene showed that the bacterium was a distinct branch in Muribaculaceae, members of which are primarily reported from gut microbiome. The name “Muribaculaceae-like bacterium associated with Kentrophoros flavus” (MLAKF) is proposed for the new bacterium. The higher 16S rRNA diversity in K. flavus and the discovery of MLAKF on the cell surface both suggest a potential bacterial consortium that interacts with the host K. flavus.
Methods for Measuring and Identifying Sounds in the Intensive Care Unit
Authors: Naef Aileen C. , Knobel Samuel E. J. , Ruettgers Nicole , Jeitziner Marie-Madlen , Holtforth Martin grosse , Zante Bjoern , Schefold Joerg C. , Nef Tobias , Gerber Stephan M.
Published: June 2022

Background

Despite many studies in the field examining excessive noise in the intensive care unit, this issue remains an ongoing problem. A limiting factor in the progress of the field is the inability to draw conclusions across studies due to the different and poorly reported approaches used. Therefore, the first goal is to present a method for the general measurement of sound pressure levels and sound sources, with precise details and reasoning, such that future studies can use these procedures as a guideline. The two procedures used in the general method will outline how to record sound pressure levels and sound sources, using sound level meters and observers, respectively. The second goal is to present the data collected using the applied method to show the feasibility of the general method and provide results for future reference.

Methods

The general method proposes the use of two different procedures for measuring sound pressure levels and sound sources in the intensive care unit. The applied method uses the general method to collect data recorded over 24-h, examining two beds in a four-bed room, via four sound level meters and four observers each working one at a time.

Results

The interrater reliability of the different categories was found to have an estimate of >0.75 representing good and excellent estimates, for 19 and 16 of the 24 categories, for the two beds examined. The equivalent sound pressure levels (LAeq) for the day, evening, and night shift, as an average of the sound level meters in the patient room, were 54.12, 53.37, and 49.05 dBA. In the 24-h measurement period, talking and human generated sounds occurred for a total of 495 (39.29% of the time) and 470 min (37.30% of the time), at the two beds of interest, respectively.

Conclusion

A general method was described detailing two independent procedures for measuring sound pressure levels and sound sources in the ICU. In a continuous data recording over 24 h, the feasibility of the proposed general method was confirmed. Moreover, good and excellent interrater reliability was achieved in most categories, making them suitable for future studies.
Knowledge, Attitudes, and Practices Toward the Prevention of COVID-19 in Bangladesh: A Systematic Review and Meta-Analysis
Authors: Raquib Ahsan , Raquib Radwan , Jamil Safayet , Hossain Ahmed , al-Mamun Firoj , Mamun Mohammed A.
Published: June 2022

Background

Numerous studies on knowledge, attitude, and practice (KAP) about the prevention of COVID-19 infections are available in Bangladeshi contexts, with results that vary significantly. However, no earlier attempt has been made to analyze the available COVID-19 KAP studies in Bangladesh, which is incorporated in this meta-analysis for the first time.

Methods

Following the PRISMA guidelines, articles relevant to COVID-19 KAP that were conducted among the Bangladeshi population were found in databases such as PubMed, Scopus, CINAHL, Google Scholar, and ResearchGate. Random-effect meta-analysis was used to generate a pooled prevalence of knowledge, attitude, and practice level toward the prevention of COVID-19 infection.

Results

This review included 18 articles that were published between March 2020 and November 2021. Overall, 89.87% (95% CI: 67.71–97.40) understood about COVID-19 symptoms, 92.09% (95% CI: 84.32–96.18) knew about how it spreads, and 79.51% (95% CI: 59.38–91.15) knew about how to treat it. The public's perception of controlling COVID-19 is mixed, with only 44.16% (95% CI: 35.74–52.93) and 60.28% (95% CI: 49.22–70.38) believing the country would win the struggle against the pandemic and the infection will be successfully controlled, respectively. Although overall COVID-19 preventative practice was good, subgroup analysis found that men had a poor practice toward controlling the infection. The practice of avoiding crowded places (70.15%) and maintaining social distance (77.17%) was found to be satisfactory in institution-based studies.

Conclusion

The findings of this study revealed that the Bangladeshi population had a good awareness of COVID-19 symptoms, treatment, attitudes, and behaviors. The findings of this study are likely to aid Bangladeshi governments and policymakers in putting evidence into action by identifying gaps and emphasizing the importance of educating the less informed public about COVID-19 transmission.
JAK1/2 Inhibitor Baricitinib Improves Skin Fibrosis and Digital Ulcers in Systemic Sclerosis
Authors: Hou Zhanying , Su Xuehan , Han Guangming , Xue Ruzeng , Chen Yangxia , Chen Ye , Wang Huan , Yang Bin , Liang Yunsheng , Ji Suyun
Published: June 2022

Background

Systemic sclerosis (SSc) is a rare disabling connective tissue disease with few available treatment options. Diffuse cutaneous systemic sclerosis (dcSSc) is associated with high mortality. A previous experiment has shown that JAK2 inhibitor can significantly improve skin fibrosis in bleomycin (BLM)-induced murine model, including reducing dermal thickening and collagen accumulation. We aimed to describe the efficacy of oral JAK1/2 inhibitor baricitinib in SSc patients, especially focusing on skin fibrosis and microvascular manifestations.

Methods

We described the different effects of oral selective JAK1, JAK2, or JAK3 inhibitor treatment in a BLM-induced skin fibrosis mouse model. Furthermore, 10 adult patients with dcSSc were treated with baricitinib. We assessed the changes in modified rodman skin score (mRSS) and digital ulcer net burden at week 12 and 24 from baseline. We also compared the absolute changes in scores on the Scleroderma Health Assessment Questionnaire (SHAQ) and a total score on the St. George's Respiratory Questionnaire (SGRQ) over a 24-week period.

Results

In the experimental mouse model of skin fibrosis, a JAK1 and JAK2 inhibitor ameliorated skin fibrosis, and a JAK2 inhibitor had the most obvious effect. Treatment with the JAK2 inhibitor also blunted the capillary rarefaction. We demonstrated that skin fibrosis and digital ulcers were significantly relieved in 10 SSc patients treated with baricitinib. The mRSS significantly improved at week 12 from baseline, with a mean change in mRSS of −8.3 [95% confidence interval (CI), −12.03 to −4.574; p = 0.0007] and improved greater at week 24 to −11.67 (95% CI, −16.84 to −6.496; p = 0.0008). Among the four patients with digital ulcers (DU), three were completely healed at week 24, the number of ulcers in another patient was significantly reduced, and there was no patient with new ulcers. Only one adverse event (AE) of herpes zoster was observed.

Conclusions

Our results indicate that selective JAK1 and JAK2 inhibitor alleviates skin fibrosis, and oral JAK1/2 inhibitor baricitinib is a potentially effective treatment for dcSSc patients with skin fibrosis and DU. Baricitinib was well-tolerated by most patients in this study. Additional large clinical trials are needed to confirm our pilot findings.

Chinese Clinical Trial Registry Number

ChiCTR2000030995.
Top 100 Cited Articles on Clinical Hematopoietic Stem Cell Transplantation: A Bibliometric Analysis
Authors: Shahzad Moazzam , Chaudhary Sibgha Gull , Anwar Iqra , Arslan Muhammad , Naseem Zehra , Fatima Naira T. , Abbas Sakina , Ali Tayyaba , Siddiqui Raheel S. , Hematti Peiman , Abhyankar Sunil H. , McGuirk Joseph P. , Mushtaq Muhammad Umair
Published: June 2022

We conducted a bibliometric analysis to identify scholarly impact and factors associated with the top 100 cited articles on clinical hematopoietic stem cell transplantation (HSCT). In January 2021, a title-specific search was conducted. Non-HSCT and pre-clinical (in-vitro and animal) studies were excluded. A total of 39,406 records were identified and a list of the top 100 articles was made. Articles included in our study were characterized by the citations received, publication year, topic, study design, authors, h-index, and institutions. Linear regression analyses were performed. The 100 most cited articles were published over 52 years from 1968 to 2020, with a maximum number of articles (n = 40) published in the 1990s decade. Top-100 articles were cited 62,002 times with a median citation count of 465 (range 336–2240). The top-cited articles originated from 12 countries. United States contributed 69 articles. The University of Washington Fred Hutchinson Cancer Center (n = 15) was the leading institution. Blood (n = 32) and New England Journal of Medicine (n = 31) made the greatest contribution, and 52 manuscripts were clinical trials. The first author's H-index significantly correlated with citation count while journal impact factor, years since publication, first author's gender, and the number of authors did not have a significant association with the number of citations. In a multivariate regression model, the first author's h-index (regression coefficient 5.46, 95% confidence interval 2.99 to 7.93, p < 0.001) independently correlated with the citation count. Our study highlights the most influential articles on clinical HSCT and provides valuable insight for future research needs of the specialty.
Novel PET Imaging of Inflammatory Targets and Cells for the Diagnosis and Monitoring of Giant Cell Arteritis and Polymyalgia Rheumatica
Authors: van der Geest Kornelis S. M. , Sandovici Maria , Nienhuis Pieter H. , Slart Riemer H. J. A. , Heeringa Peter , Brouwer Elisabeth , Jiemy William F.
Published: June 2022

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two interrelated inflammatory diseases affecting patients above 50 years of age. Patients with GCA suffer from granulomatous inflammation of medium- to large-sized arteries. This inflammation can lead to severe ischemic complications (e.g., irreversible vision loss and stroke) and aneurysm-related complications (such as aortic dissection). On the other hand, patients suffering from PMR present with proximal stiffness and pain due to inflammation of the shoulder and pelvic girdles. PMR is observed in 40–60% of patients with GCA, while up to 21% of patients suffering from PMR are also affected by GCA. Due to the risk of ischemic complications, GCA has to be promptly treated upon clinical suspicion. The treatment of both GCA and PMR still heavily relies on glucocorticoids (GCs), although novel targeted therapies are emerging. Imaging has a central position in the diagnosis of GCA and PMR. While [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) has proven to be a valuable tool for diagnosis of GCA and PMR, it possesses major drawbacks such as unspecific uptake in cells with high glucose metabolism, high background activity in several non-target organs and a decrease of diagnostic accuracy already after a short course of GC treatment. In recent years, our understanding of the immunopathogenesis of GCA and, to some extent, PMR has advanced. In this review, we summarize the current knowledge on the cellular heterogeneity in the immunopathology of GCA/PMR and discuss how recent advances in specific tissue infiltrating leukocyte and stromal cell profiles may be exploited as a source of novel targets for imaging. Finally, we discuss prospective novel PET radiotracers that may be useful for the diagnosis and treatment monitoring in GCA and PMR.
Disease-Ligand Identification Based on Flexible Neural Tree
Authors: Yang Bin , Bao Wenzheng , Chen Baitong
Published: June 2022

In order to screen the disease-related compounds of a traditional Chinese medicine prescription in network pharmacology research accurately, a new virtual screening method based on flexible neural tree (FNT) model, hybrid evolutionary method and negative sample selection algorithm is proposed. A novel hybrid evolutionary algorithm based on the Grammar-guided genetic programming and salp swarm algorithm is proposed to infer the optimal FNT. According to hypertension, diabetes, and Corona Virus Disease 2019, disease-related compounds are collected from the up-to-date literatures. The unrelated compounds are chosen by negative sample selection algorithm. ECFP6, MACCS, Macrocycle, and RDKit are utilized to numerically characterize the chemical structure of each compound collected, respectively. The experiment results show that our proposed method performs better than classical classifiers [Support Vector Machine (SVM), random forest (RF), AdaBoost, decision tree (DT), Gradient Boosting Decision Tree (GBDT), KNN, logic regression (LR), and Naive Bayes (NB)], up-to-date classifier (gcForest), and deep learning method (forgeNet) in terms of AUC, ROC, TPR, FPR, Precision, Specificity, and F1. MACCS method is suitable for the maximum number of classifiers. All methods perform poorly with ECFP6 molecular descriptor.
Transduction of Systemically Administered Adeno-Associated Virus in the Colonic Enteric Nervous System and c-Kit Cells of Adult Mice
Authors: Wang Lixin , Yuan Pu-Qing , Challis Collin , Ravindra Kumar Sripriya , Taché Yvette
Published: June 2022

Systemic delivery of adeno-associated virus (AAV) vectors transduces the enteric nervous system. However, less is known on the mapping and morphological and neurochemical characterization in the adult mouse colon. We used AAV9-CAG-GFP (AAV9) and AAV-PHP.S-hSyn1-tdTomato farnesylated (PHP.S-tdTf) to investigate the segmental distribution, morphologies and neurochemical coding of the transduction. The vectors were retro-orbitally injected in male and female adult mice, and 3 weeks later, the colon was prepared for microcopy with or without immunohistochemistry for neuronal and non-neuronal markers. In contrast to the distributions in neonatal and juvenile rodents, the AAV transduction in neurons and/or nerve fibers was the highest in the proximal colon, decreased gradually in the transverse, and was sparse in the distal colon without difference between sexes. In the proximal colon, the AAV9-transduced myenteric neurons were unevenly distributed. The majority of enteric neurons did not have AAV9 expression in their processes, except those with big soma with or without variously shaped dendrites, and a long axon. Immunolabeling demonstrated that about 31% neurons were transduced by AAV9, and the transduction was in 50, 28, and 31% of cholinergic, nitrergic, and calbindin-positive myenteric neurons, respectively. The nerve fiber markers, calcitonin gene-related peptide alpha, tyrosine hydroxylase or vasoactive intestinal polypeptide co-localized with AAV9 or PHP.S-tdTf in the mucosa, and rarely in the myenteric plexus. Unexpectedly, AAV9 expression appeared also in a few c-Kit immunoreactive cells among the heavily populated interstitial cells of Cajal (ICC). In the distal colon, the AAV transduction appeared in a few nerve fibers mostly the interganglionic strands. Other types of AAV9 and AAV-PHP vectors induced a similar colonic segmental difference which is not colon specific since neurons were transduced in the small intestine and gastric antrum, while little in the gastric corpus and none in the lower esophagus.

Conclusion

These findings demonstrate that in adult mice colon that there is a rostro-caudal decrease in the transduction of systemic delivery of AAV9 and its variants independent of sex. The characterization of AAV transduction in the proximal colon in cholinergic and nitrergic myenteric neurons along with a few ICC suggests implications in circuitries regulating motility.
Influence of Selective Dopamine Agonist Ropinirole on Conditioned Place Preference and Somatic Signs of Morphine Withdrawal in Rats
Authors: Shahzadi Andleeb , Yunusoglu Oruc , Karabulut Enes , Sonmez Haktan , Yazici Zeliha
Published: June 2022

The underlying mechanism of dependence and rewarding effects of morphine is imperative to understand. The primary aim of this study was to investigate whether ropinirole D2/3 agonist affects the rewarding and reinforcing properties of morphine-induced conditioned place preference (CPP) and withdrawal syndromes in rats. On day one, the animals were randomly divided to conduct the pre-test. The morphine (10 mg/kg, i.p.) and/or saline was administered on alternate days in an 8-day CPP session. On day 10, 15 min prior to the post-conditioning test (expression), a single dose of ropinirole (1, 2, and 5 mg/kg, i.p.) was given to rats. In extinction session, ropinirole was injected daily, and CPP was extinguished by repeated testing, with intervals of 3 days. Finally, reinstatement was assessed by administering ropinirole (1, 2, and 5 mg/kg) 15 min before the morphine injection. Morphine dependence was developed by administering increasing doses of morphine (10–50 mg/kg, i.p.). To assess withdrawal symptoms, ropinirole (1, 2, and 5 mg/kg) was injected 15 min before naloxone (2 mg/kg, s.c.) administration. The present study confirms that ropinirole attenuates expression and reinstatement of CPP, while it precipitates the extinction of morphine-induced CPP. Naloxone-precipitated morphine withdrawal symptoms, including wet dog shakes and weight loss, were attenuated although jumping was increased by a single ropinirole injection. Thus, ropinirole was influential in attenuating expression, reducing drug seeking and weakening reinstatement via the dopaminergic system. These findings show that ropinirole might affect neuro-adaptive changes related to dependence.
Beyond the Baroreflex: A New Measure of Autonomic Regulation Based on the Time-Frequency Assessment of Variability, Phase Coherence and Couplings
Authors: Clemson Philip T. , Hoag Jeffrey B. , Cooke William H. , Eckberg Dwain L. , Stefanovska Aneta
Published: June 2022

For decades the role of autonomic regulation and the baroreflex in the generation of the respiratory sinus arrhythmia (RSA) - modulation of heart rate by the frequency of breathing - has been under dispute. We hypothesized that by using autonomic blockers we can reveal which oscillations and their interactions are suppressed, elucidating their involvement in RSA as well as in cardiovascular regulation more generally. R-R intervals, end tidal CO2, finger arterial pressure, and muscle sympathetic nerve activity (MSNA) were measured simultaneously in 7 subjects during saline, atropine and propranolol infusion. The measurements were repeated during spontaneous and fixed-frequency breathing, and apnea. The power spectra, phase coherence and couplings were calculated to characterise the variability and interactions within the cardiovascular system. Atropine reduced R-R interval variability (p < 0.05) in all three breathing conditions, reduced MSNA power during apnea and removed much of the significant coherence and couplings. Propranolol had smaller effect on the power of oscillations and did not change the number of significant interactions. Most notably, atropine reduced R-R interval power in the 0.145–0.6 Hz interval during apnea, which supports the hypothesis that the RSA is modulated by a mechanism other than the baroreflex. Atropine also reduced or made negative the phase shift between the systolic and diastolic pressure, indicating the cessation of baroreflex-dependent blood pressure variability. This result suggests that coherent respiratory oscillations in the blood pressure can be used for the non-invasive assessment of autonomic regulation.
Differential Association of Wheat and Rice Consumption With Overweight/Obesity in Chinese Adults: China Health and Nutrition Survey 1991–2015
Authors: Zhang Jiguo , Wang Zhihong , Du Wenwen , Huang Feifei , Zhang Bing , Wang Huijun
Published: June 2022

Wheat and rice are the main staple foods in China and likely have a major influence on health. This analysis examined the potential association between wheat and rice consumption and the risk of overweight/obesity in Chinese adults. We used data collected in the China Health and Nutrition Survey (CHNS) from 1991 to 2015. Adults aged 18–80 years old (n = 11,503) were included in the present analysis, for whom questionnaires and anthropometric data were collected during at least two waves. We constructed three-level mixed-effect linear regression models to estimate body mass index (BMI) in relation to wheat and rice intakes and performed three-level mixed-effect logistic regression models to assess the risk of overweight/obesity. Women showed significant BMI increases of 0.14 (95% CI: 0.04, 0.24) from a higher intake of wheat but not from a higher intake of rice when adjusted for all potential confounders. Comparing the highest quartiles of intake of wheat with non-consumers in men and women, odds ratios (ORs; 95% CI) of overweight/obesity were 1.45 (1.15, 1.85) and 1.26 (1.00, 1.60), respectively. In men, there was an inverse association with the risk of overweight/obesity in the comparison of the highest quartiles of intake of rice (OR: 0.73; 95% CI: 0.55, 0.96) and non-consumers when adjusted for all potential confounders. Higher intake of wheat was positively associated with the risk of overweight/obesity among Chinese adults. Further, there was an inverse association between rice intake with overweight/obesity in Chinese men but not in women.
Relationships Between Biological Heavy Metals and Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Liu Lin , Chen Jie , Liu Chang , Luo Yuxuan , Chen Jiayun , Fu Yuanyuan , Xu Yajie , Wu Haili , Li Xue , Wang Hui
Published: June 2022

Introduction

Heavy metals were classified as essential, probably essential, and potentially toxic in the general population. Until now, it has been reported inconsistently on the association between heavy metals and BC. In this meta-analysis, we aimed to assess the association between heavy metals and BC and review the potential mechanisms systematically.

Methods

We searched for epidemiological studies in English about the association between heavy metals and BC published before September 2020 in PubMed, Web of Science, and Embase databases. In total 36 studies, comprising 4,151 individuals from five continents around the world were identified and included.

Results

In all biological specimens, Cu, Cd, and Pb concentrations were higher, but Zn and Mn concentrations were lower in patients with BC than in non-BC participants [SMD (95% CIs): 0.62 (0.12, 1.12); 1.64 (0.76, 2.52); 2.03 (0.11, 3.95); −1.40 (−1.96, −0.85); −2.26 (−3.39, −1.13); p = 0.01, 0.0003, 0.04, <0.0001, <0.0001]. Specifically, higher plasma or serum Cu and Cd, as well as lower Zn and Mn, were found in cases [SMD (95% CIs): 0.98 (0.36, 1.60); 2.55 (1.16, 3.94); −1.53 (−2.28, −0.78); −2.40 (−3.69, −1.10); p = 0.002, 0.0003, <0.0001, 0.0003]; in hair, only lower Zn was observed [SMD (95% CIs): −2.12 (−3.55, −0.68); p = 0.0004]. Furthermore, the status of trace elements probably needs to be re-explored, particularly in BC. More prospective studies, randomized clinical trials, and specific pathogenic studies are needed to prevent BC. The main mechanisms underlying above-mentioned findings are comprehensively reviewed.

Conclusion

For BC, this review identified the current knowledge gaps which we currently have in understanding the impact of different heavy metals on BC.

Systematic Review Registration

www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020176934, identifier: CRD42020176934.
Exploring the Antioxidant and Structural Properties of Black Bean Protein Hydrolysate and Its Peptide Fractions
Authors: Chen Yin , Zheng Zhaojun , Ai Zixuan , Zhang Yan , Tan Chin Ping , Liu Yuanfa
Published: June 2022

A great deal of attention has been paid to charactering the protein hydrolysates prepared by enzymatic hydrolysis, while the influence of molecular weight (MW) distributions on the resultant hydrolysates remains unclear. This study aimed to explore the physicochemical and antioxidant characteristics of protein hydrolysate and its peptide fractions. Bromelain has been commonly used to hydrolyze black bean protein via response surface methodology (RSM). The optimal hydrolysis parameters were observed at 52°C, pH 7, E/S ratio of 2.2 (ratio of enzyme to substrate), and 4 h. Under these parameters, the hydrolysate (BPH) presented DPPH radical scavenging activity and Fe2+ chelating activity with IC50 values of 100.08 ± 2.42 and 71.49 ± 0.81 μg/mL, respectively. This might be attributed to structural characteristics, varying with different molecular weight distributions. Interestingly, among BPH and its peptide fractions, peptides smaller than 3 kDa were noted to exhibit the strongest DPPH and ABTS radical scavenging activity. More intriguingly, this peptide fraction (<3 kDa) could predominantly prolong the induction period of sunflower oil, which was, respectively increased to 1.31 folds. This may be due to high proportions of hydrophobic amino acids. Unexpectedly, the optimal Fe2+ chelating activity was observed in the peptide fraction measuring at 3–10 kDa, showing highly positive correlations with histidine and arginine. These identified peptide fractions derived from black bean protein can therefore be employed for food fortification acting as natural antioxidant alternatives.
The Clinical Characteristics and Prognosis of AYA and Older Adult ETP-ALL/LBL: A Real-World Multicenter Study in China
Authors: Xiao Jinyan , Cai Zihong , Wang Hao , Li Xuekai , Zhou Biqi , Liu Yujie , Wang Ying , Xu Peipei , Wang Li , Wu Depei , Dou Liping , Zhou Hongsheng , Xu Yang
Published: June 2022

Early T-cell precursor (ETP) lymphoblastic leukemia/lymphoma is a high-risk T lymphoblastic leukemia/lymphoma (T-ALL/LBL) subgroup. We performed a real-world multicenter study to explore the clinical characteristics and prognosis of adolescent and young adults (AYA) and older adult ETP leukemia/lymphoma. A total of 103 patients with ETP-ALL/LBL in five centers in China between January 2016 and February 2021 were included in this study. The median age was 29 years (range, 15–70 years). Next-generation sequencing was performed in 94 patients and revealed that NOTCH1 (35.1%, 33 cases) was the most frequently mutated gene, followed by JAK3 (16.0%, 15 cases), PHF6 (13.80%, 13 cases) and EZH2 (11.70%, 11 cases). Complete remission (CR) was obtained in 74.2% (72/97) of patients, and 6 relapsed/refractory patients received a decitabine combined with AAG priming regimen as reinduction therapy with a CR rate of 50%. With a median follow-up of 18 months (0.5–60 months), the 2-year overall survival (OS) and relapse-free survival (RFS) rates for the entire cohort were 54% and 57.7%, respectively. Allogeneic stem cell transplantation (allo-SCT) was performed in 59.8% (58/97) of patients. After landmark analysis at 6 months, the 2-year OS rates was 77% of patients with allo-SCT at CR1 and 25% of patients with chemotherapy alone (p < 0.001). A multivariate analysis suggested that allo-SCT and CR after the first course induction were independent prognostic factors for OS. Collectively, we reported the largest cohort study with AYA and older adult ETP-ALL/LBL, and we found that ETP-ALL/LBL was highly invasive and had a poor long-term prognosis. Allo-SCT could significantly improve ETP-ALL/LBL patient survival.
The Studies of Prognostic Factors and the Genetic Polymorphism of Methylenetetrahydrofolate Reductase C667T in Thymic Epithelial Tumors
Authors: Yan Miaolong , Wu Jiayuan , Xue Min , Mo Juanfen , Zheng Li , Zhang Jun , Gao Zhenzhen , Bao Yi
Published: June 2022

Objective

To describe the clinical features of a cohort of patients with thymic epithelial tumors (TETs) and to analyze their prognostic factors. In particular, we investigated the correlation between the genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) C667T and the incidence of TETs.

Methods

Pathological records were reviewed from the database of the Second Affiliated Hospital of Jiaxing University, from January 2010 to December 2020, and 84 patients with TETs were recruited for this study. Univariate and multivariate analyses were performed to determine the prognostic factors. The genetic polymorphism of MTHFR C667T was examined in the patients with TETs and in a group of healthy individuals. The correlation between MTHFR transcriptional levels and methylation was analyzed using The Cancer Genome Atlas (TCGA) thymoma dataset from the cBioPortal platform.

Results

Kaplan–Meier univariate survival analysis showed that sex, age, the maximum tumor diameter, surgery, chemotherapy, radiotherapy, WHO histological classification, Masaoka–Koga stage, and 8th UICC/AJCC TNM staging, were statistically significantly correlated with the prognosis of patients with TETs. The Masaoka–Koga stage and 8th UICC/AJCC TNM staging were strongly correlated with each other in this study (r=0.925, P<0.001). Cox multivariate survival analysis showed that the maximum tumor diameter, Masaoka–Koga stage, and 8th UICC/AJCC TNM staging were independent prognostic factors affecting the overall survival (OS) of patients with TETs (P<0.05). The MTHFR C667T genotype (χ2 = 7.987, P=0.018) and allele distribution (χ2 = 5.750, P=0.016) were significantly different between the patients and healthy controls. CT heterozygous and TT homozygous genotypes at this MTHFR polymorphism significantly increased the risk of TETs (odds ratio [OR] =4.721, P=0.008). Kaplan–Meier univariate survival analysis showed that there was no correlation between different genotypes and the prognosis of TETs (CC versus CT + TT, χ2 =0.003, P=0.959). Finally, a negative correlation between the transcriptional and methylation levels of MTHFR was observed in the TCGA thymoma dataset (r=-0.24, P=0.010).

Conclusions

The Masaoka–Koga stage, 8th UICC/AJCC TNM staging, and maximum tumor diameter were independent prognostic factors for TETs. Reduced methylation levels of MTHFR and particular polymorphic variants may contribute to the susceptibility to developing TETs.
Preoperative Prediction of Inferior Vena Cava Wall Invasion of Tumor Thrombus in Renal Cell Carcinoma: Radiomics Models Based on Magnetic Resonance Imaging
Authors: Sun Zhaonan , Cui Yingpu , Xu Chunru , Yu Yanfei , Han Chao , Liu Xiang , Lin Zhiyong , Wang Xiangpeng , Li Changxin , Zhang Xiaodong , Wang Xiaoying
Published: June 2022

Objective

To develop radiomics models to predict inferior vena cava (IVC) wall invasion by tumor thrombus (TT) in patients with renal cell carcinoma (RCC).

Methods

Preoperative MR images were retrospectively collected from 91 patients with RCC who underwent radical nephrectomy (RN) and thrombectomy. The images were randomly allocated into a training (n = 64) and validation (n = 27) cohort. The inter-and intra-rater agreements were organized to compare masks delineated by two radiologists. The masks of TT and IVC were manually annotated on axial fat-suppression T2-weighted images (fsT2WI) by one radiologist. The following models were trained to predict the probability of IVC wall invasion: two radiomics models using radiomics features extracted from the two masks (model 1, radiomics model_IVC; model 2, radiomics model_TT), two combined models using radiomics features and radiological features (model 3, combined model_IVC; model 4, combined model_TT), and one radiological model (model 5) using radiological features. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were applied to validate the discriminatory effect and clinical benefit of the models.

Results

Model 1 to model 5 yielded area under the curves (AUCs) of 0.881, 0.857, 0.883, 0.889, and 0.769, respectively, in the validation cohort. No significant differences were found between these models (p = 0.108-0.951). The dicision curve analysis (DCA) showed that the model 3 had a higher overall net benefit than the model 1, model 2, model 4, and model 5.

Conclusions

The combined model_IVC (model 3) based on axial fsT2WI exhibited excellent predictive performance in predicting IVC wall invasion status.
Recent Progress on Therapeutic Vaccines for Breast Cancer
Authors: Zhang Lianru , Zhou Xipeng , Sha Huizi , Xie Li , Liu Baorui
Published: June 2022

Breast cancer remains the most frequently diagnosed malignancy worldwide. Advanced breast cancer is still an incurable disease mainly because of its heterogeneity and limited immunogenicity. The great success of cancer immunotherapy is paving the way for a new era in cancer treatment, and therapeutic cancer vaccination is an area of interest. Vaccine targets include tumor-associated antigens and tumor-specific antigens. Immune responses differ in different vaccine delivery platforms. Next-generation sequencing technologies and computational analysis have recently made personalized vaccination possible. However, only a few cases benefiting from neoantigen-based treatment have been reported in breast cancer, and more attention has been given to overexpressed antigen-based treatment, especially human epidermal growth factor 2-derived peptide vaccines. Here, we discuss recent advancements in therapeutic vaccines for breast cancer and highlight near-term opportunities for moving forward.
Multi-Hit White Matter Injury-Induced Cerebral Palsy Model Established by Perinatal Lipopolysaccharide Injection
Authors: Liu Le , Fang Liwei , Duan Boyang , Wang Yue , Cui Zhenzhen , Yang Li , Wu De
Published: June 2022

Cerebral palsy (CP) is a group of permanent, but not unchanging, disorders of movement and/or posture and motor function. Since the major brain injury associated with CP is white matter injury (WMI), especially, in preterm infants, we established a “multi-hit” rat model to mimic human WMI in symptomatology and at a histological level. In our WMI model, pups suffering from limb paresis, incoordination, and direction difficulties fit the performance of CP. Histologically, they present with fewer neural cells, inordinate fibers, and more inflammatory cell infiltration, compared to the control group. From the electron microscopy results, we spotted neuronal apoptosis, glial activation, and myelination delay. Besides, the abundant appearance of IBA1-labeled microglia also implied that microglia play a role during neuronal cell injury. After activation, microglia shift between the pro-inflammatory M1 type and the anti-inflammatory M2 type. The results showed that LPS/infection stimulated IBA1 + (marked activated microglia) expression, downregulated CD11c + (marked M1 phenotype), and upregulated Arg 1 + (marked M2 phenotype) protein expression. It indicated an M1 to M2 transition after multiple infections. In summary, we established a “multi-hit” WMI-induced CP rat model and demonstrated that the microglial activation correlates tightly with CP formation, which may become a potential target for future studies.
Alterations and Potential Applications of Gut Microbiota in Biological Therapy for Inflammatory Bowel Diseases
Authors: Pu Dan , Zhang Zhe , Feng Baisui
Published: June 2022

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a chronic immune-mediated inflammatory disorder of the gastrointestinal tract that is closely associated with dysbiosis of the intestinal microbiota. Currently, biologic agents are the mainstream therapies for IBD. With the increasing incidence of IBD, limitations of biologic agents have gradually emerged during treatment. Recent studies have indicated that gut microbiota is highly correlated with the efficacy of biologic agents. This review focuses on alterations in both the components and metabolites of gut microbiota during biological therapy for IBD, systematically summarises the specific gut microbiota closely related to the clinical efficacy, and compares current predictive models for the efficacy of biologics, further highlighting the predictive value of intestinal microbiota. Based on the mechanistic analysis of faecal microbiota transplantation (FMT) and biologic agents, a new therapeutic strategy, comprising a combination of FMT and biologics, has been proposed as a promising treatment for IBD with improved efficacy.
Real-Life Experience of Regorafenib in Patients With Advanced Hepatocellular Carcinoma
Authors: Hou Jing-Yu , Xiao Ya-ting , Huang Jing-Bo , Jiang Xin-Hua , Jiang Kai , Li Xun , Xu Li , Chen Min-Shan
Published: June 2022

Background: The RESORCE trial reported that regorafenib was effective as the second-line treatment for patients with hepatocellular carcinoma (HCC) after progression on sorafenib. Real-world data are needed to assess clinical outcomes and adverse events in the setting of daily practice.

Objective: We aimed to evaluate the efficacy and safety of regorafenib after disease progression with sorafenib in Chinese patients with advanced HCC.

Patients and Methods: A total of 41 patients with advanced HCC who did not respond to sorafenib and followed a regorafenib regimen were enrolled in this retrospective study. Overall survival (OS), progression-free survival (PFS), radiological responses, and adverse events (AEs) were evaluated. Survival curves were compared by using the log-rank test and constructed with the Kaplan–Meier method.

Results: The median PFS with regorafenib was 6.6 months (range: 5.0–8.2 months), and the median OS with regorafenib was not reached. The 1-year OS rate of regorafenib was 66.4%. The median OS of sequential sorafenib to regorafenib treatment was 35.3 months [95% confidence interval (CI), 24.3–46.3], and the 2-year OS rate of sequential sorafenib to regorafenib treatment was 74.4%. The most common AEs of regorafenib treatment were elevated aspartate aminotransferase [17/41 patients (41.5%)], elevated alanine aminotransferase [16/41 patients (39%)] and hand-foot syndrome [14/41 patients (34.1%)].

Conclusion: Regorafenib appears to be safe and clinically effective in patients with advanced HCC who progressed on first-line sorafenib.
Stochastic Methods and Complexity Science in Climate Research and Modeling
Authors: Franzke Christian L. E. , Blender Richard , O’Kane Terence J. , Lembo Valerio
Published: June 2022

The 2021 Nobel prize for physics was awarded to two climate scientists, Syukuro Manabe and Klaus Hasselmann, and the physicist Giorgio Parisi. While at first sight the work of Parisi seems not to be related to climate science, this is not the case. Giorgio Parisi developed and contributed to many complexity science methods which are nowadays widely used in climate science. Giorgi Parisi also was involved in the development of the “stochastic resonance” idea to explain paleoclimate variability, while Klaus Hasselmann developed stochastic climate models. Here we review and discuss their work from a complex and stochastic systems perspective in order to highlight those aspects of their work. For instance, fractal and multi-fractal analysis of climate data is now widely used and many weather prediction and climate models contain stochastic parameterizations, topics Parisi and Hasselmann have pioneered. Furthermore, Manabe’s work was key to understanding the effects of anthropogenic climate change by the development of key advances in the parameterization of convection and radiative forcing in climate models. We discuss also how their inventive research has shaped current climate research and is still influencing climate modeling and future research directions.
Effect of Core Training on Skill Performance Among Athletes: A Systematic Review
Authors: Luo Shengyao , Soh Kim Geok , Soh Kim Lam , Sun He , Nasiruddin Nasnoor Juzaily Mohd , Du Congxin , Zhai Xiuwen
Published: June 2022

Background:This study aims to present a critical review of the existing literature on the effect of core training on athletes’ skill performance, and to provide recommendations and suggest future research directions for both coaches and researchers.

Methods:The data in this study were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We collected studies in the literature using prominent academic and scientific databases such as Ebscohost, Scopus, PubMed, Web of Science, and Google Scholar. Only 16 of the 119 studies met all of the inclusion criteria, and were thus included in the systematic review. Each study’s quality was determined using the PEDro scale. The scoring of 16 studies ranges from 2 to 5.

Results:Core training could potentially improve skill performance among football, handball, basketball, swimming, dancing, Karate, Muay Thai, gymnasts, volleyball, badminton, and golf players.

Conclusion:Compared with the traditional training methods, core training is a new strength training method. Strong core muscles function as hubs in the biological motor chain, which create a fulcrum for the four limbs’ strength and establish a channel for the cohesion, transmission, and integration of the upper and lower limbs. In other words, core training optimizes the transfer and overall control of motion and force to the terminal segment within athletic actions. Meanwhile, core training could increase stability and stiffness in the spine to reduce unrequired “energy leaks” and torso movement during the exertion of external loads. This mechanism could help athletes achieve better skill performance. Therefore, this review suggests that core training should be considered integrated into athletes’ daily training routines.

Systematic Review Registration: [https://inplasy.com/], identifier [INPLASY2021100013].
The Developmental Delay of Seedlings With Cotyledons Only Confers Stress Tolerance to Suaeda aralocaspica (Chenopodiaceae) by Unique Performance on Morphology, Physiology, and Gene Expression
Authors: Cao Jing , Li Xiaorong , Chen Ling , He Meixiang , Lan Haiyan
Published: June 2022

Cotyledons play an important role in seedling establishment, although they may just exist for a short time and become senescent upon the emergence of euphylla. So far, the detailed function of cotyledons has not been well understood. Suaeda aralocaspica is an annual halophyte distributed in cold deserts; its cotyledons could exist for a longer time, even last until maturity, and they must exert a unique function in seedling development. Therefore, in this study, we conducted a series of experiments to investigate the morphological and physiological performances of cotyledons under salt stress at different developmental stages. The results showed that the cotyledons kept growing slowly to maintain the normal physiological activities of seedlings by balancing phytohormone levels, accumulating osmoprotectants and antioxidants, and scavenging reactive oxygen species (ROS). Salt stress activated the expression of osmoprotectant-related genes and enhanced the accumulation of related primary metabolites. Furthermore, differentially expressed transcriptional profiles of the cotyledons were also analyzed by cDNA-AFLP to gain an understanding of cotyledons in response to development and salt stress, and the results revealed a progressive increase in the expression level of development-related genes, which accounted for a majority of the total tested TDFs. Meanwhile, key photosynthetic and important salt stress-related genes also actively responded. All these performances suggest that “big cotyledons” are experiencing a delayed but active developmental process, by which S. aralocaspica may survive the harsh condition of the seedling stage.
Exploiting Unreduced Gametes for Improving Ornamental Plants
Authors: Xie Li , Ke Li-zhen , Lu Xiao-qi , Chen Jianjun , Zhang Zhi-sheng
Published: June 2022

The formation of gametes with somatic chromosome number or unreduced gametes (2n gametes) is an important process involved in the origin of polyploid plants in nature. Unreduced gametes are the result of meiotic mutations occurring during micro- and mega-sporogenesis. 2n gametes have been identified or artificially induced in a large number of plant species. Breeding of plants through 2n gametes can be advantageous because it combines genetic effects of polyploidy with meiotic recombination and sexual hybridization to produce tremendous genetic variation and heterosis. 2n gametes also occur in ornamental plants, but the potential of using 2n gametes in ornamental plant breeding has not been extensively exploited. Ornamental plants are primarily produced for their esthetic appearance and novelty, not for food and yield, and they can be readily propagated through vegetative means. Triploids, tetraploids, and plants with even higher ploidy levels produced through 2n gametes can be propagated through tissue culture to fix their phenotypes, thus leading to the development of new cultivars. In this review article, we intend to discuss the mechanisms underlying the formation of 2n gametes, techniques for 2n gamete identification, methods for enhancing 2n gamete formation, and the current status in the use of 2n gametes for development of novel ornamental plants. We believe that polyploidy breeding through 2n gametes represents a viable way of developing new cultivars, new species, and even new genera of ornamental plants.
Strengthening the Bridge Between Academic and the Industry Through the Academia-Industry Collaboration Plan Design Model
Authors: Ahmed Farah , Fattani Muhammad Tahir , Ali Syed Rizwan , Enam Rabia Noor
Published: June 2022

The study has been undertaken to integrate two different aspects of the triple helix model: universities and the industry. Special attention has been paid to the prevailing difference between the two, hampering their working as a coherent unit. Integrating the existing knowledge in the study, we proposed the Academia-Industry Collaboration Plan (AICP) design model. The model comprises processes, methods or approaches, and tools. Processes serve as a road map to third parties for establishing collaboration between academia and the industry. It has all the essential process models and a series of steps that help minimize the organizational complexity of the collaboration process between academia and the industry. Methods or approaches serve the purpose of implementing those processes effectively. Finally, appropriate tools are selected to integrate possible collaboration improvements that lead to innovation.