bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental Concentrations of Sulfonamides Can Alter Bacterial Structure and Induce Diatom Deformities in Freshwater Biofilm Communities
Authors: Kergoat Laura , Besse-Hoggan Pascale , Leremboure Martin , Beguet Jérémie , Devers Marion , Martin-Laurent Fabrice , Masson Matthieu , Morin Soizic , Roinat Amélie , Pesce Stéphane , Bonnineau Chloé
Published: May 2021

Since the early 1920s, the intensive use of antibiotics has led to the contamination of the aquatic environment through diffuse sources and wastewater effluents. The antibiotics commonly found in surface waters include sulfamethoxazole (SMX) and sulfamethazine (SMZ), which belong to the class of sulfonamides, the oldest antibiotic class still in use. These antibiotics have been detected in all European surface waters with median concentrations of around 50 ng L–1 and peak concentrations of up to 4–6 μg L–1. Sulfonamides are known to inhibit bacterial growth by altering microbial production of folic acid, but sub-lethal doses may trigger antimicrobial resistance, with unknown consequences for exposed microbial communities. We investigated the effects of two environmentally relevant concentrations (500 and 5,000 ng L–1) of SMZ and SMX on microbial activity and structure of periphytic biofilms in stream mesocosms for 28 days. Measurement of sulfonamides in the mesocosms revealed contamination levels of about half the nominal concentrations. Exposure to sulfonamides led to slight, transitory effects on heterotrophic functions, but persistent effects were observed on the bacterial structure. After 4 weeks of exposure, sulfonamides also altered the autotrophs in periphyton and particularly the diversity, viability and cell integrity of the diatom community. The higher concentration of SMX tested decreased both diversity (Shannon index) and evenness of the diatom community. Exposure to SMZ reduced diatom species richness and diversity. The mortality of diatoms in biofilms exposed to sulfonamides was twice that in non-exposed biofilms. SMZ also induced an increase in diatom teratologies from 1.1% in non-exposed biofilms up to 3% in biofilms exposed to SMZ. To our knowledge, this is the first report on the teratological effects of sulfonamides on diatoms within periphyton. The increase of both diatom growth rate and mortality suggests a high renewal of diatoms under sulfonamide exposure. In conclusion, our study shows that sulfonamides can alter microbial community structures and diversity at concentrations currently present in the environment, with unknown consequences for the ecosystem. The experimental set-up presented here emphasizes the interest of using natural communities to increase the ecological realism of ecotoxicological studies and to detect potential toxic effects on non-target species.
Gut Microbiota Dysbiosis Induced by Intracerebral Hemorrhage Aggravates Neuroinflammation in Mice
Authors: Yu Xiaobo , Zhou Guoyang , Shao Bo , Zhou Hang , Xu Chaoran , Yan Feng , Wang Lin , Chen Gao , Li Jianru , Fu Xiongjie
Published: May 2021

Intracerebral hemorrhage (ICH) induces a strong hematoma-related neuroinflammatory reaction and alters peripheral immune homeostasis. Recent research has found that gut microbiota plays a role in neurodegeneration and autoimmune diseases by regulating immune homeostasis and neuroinflammation. Therefore, we investigated the relationship between ICH, microbiota alteration, and immune responses after hematoma-induced acute brain injury. In our study, we used a mouse model of ICH, and 16S ribosomal RNA sequencing showed that ICH causes gut microbiota dysbiosis, which in turn affects ICH outcome through immune-mediated mechanisms. There was prominent reduced species diversity and microbiota overgrowth in the dysbiosis induced by ICH, which may reduce intestinal motility and increase gut permeability. In addition, recolonizing ICH mice with a normal health microbiota ameliorates functional deficits and neuroinflammation after ICH. Meanwhile, cell-tracking studies have demonstrated the migration of intestinal lymphocytes to the brain after ICH. In addition, therapeutic transplantation of fecal microbiota improves intestinal barrier damage. These results support the conclusion that the gut microbiome is a target of ICH-induced systemic alteration and is considered to have a substantial impact on ICH outcome.
Human Pathogenic Bacteria Detected in Rainwater: Risk Assessment and Correlation to Microbial Source Tracking Markers and Traditional Indicators
Authors: Denissen Julia K. , Reyneke Brandon , Waso Monique , Khan Sehaam , Khan Wesaal
Published: May 2021

Roof-harvested rainwater (RHRW) was investigated for the presence of the human pathogenic bacteria Mycobacterium tuberculosis (M. tuberculosis), Yersinia spp. and Listeria monocytogenes (L. monocytogenes). While Yersinia spp. were detected in 92% (n = 25) of the RHRW samples, and L. monocytogenes and M. tuberculosis were detected in 100% (n = 25) of the samples, a significantly higher mean concentration (1.4 × 103 cells/100 mL) was recorded for L. monocytogenes over the sampling period. As the identification of appropriate water quality indicators is crucial to ensure access to safe water sources, correlation of the pathogens to traditional indicator organisms [Escherichia coli (E. coli) and Enterococcus spp.] and microbial source tracking (MST) markers (Bacteroides HF183, adenovirus and Lachnospiraceae) was conducted. A significant positive correlation was then recorded for E. coli versus L. monocytogenes (r = 0.6738; p = 0.000), and Enterococcus spp. versus the Bacteroides HF183 marker (r = 0.4071; p = 0.043), while a significant negative correlation was observed for M. tuberculosis versus the Bacteroides HF183 marker (r = −0.4558; p = 0.022). Quantitative microbial risk assessment indicated that the mean annual risk of infection posed by L. monocytogenes in the RHRW samples exceeded the annual infection risk benchmark limit (1 × 10–4 infections per person per year) for intentional drinking (∼10–4). In comparison, the mean annual risk of infection posed by E. coli was exceeded for intentional drinking (∼10–1), accidental consumption (∼10–3) and cleaning of the home (∼10–3). However, while the risk posed by M. tuberculosis for the two relevant exposure scenarios [garden hosing (∼10–5) and washing laundry by hand (∼10–5)] was below the benchmark limit, the risk posed by adenovirus for garden hosing (∼10–3) and washing laundry by hand (∼10–3) exceeded the benchmark limit. Thus, while the correlation analysis confirms that traditional indicators and MST markers should be used in combination to accurately monitor the pathogen-associated risk linked to the utilisation of RHRW, the integration of QMRA offers a more site-specific approach to monitor and estimate the human health risks associated with the use of RHRW.
A Chimeric Cationic Peptide Composed of Human β-Defensin 3 and Human β-Defensin 4 Exhibits Improved Antibacterial Activity and Salt Resistance
Authors: Yu Wenjing , Ning Nianzhi , Xue Ying , Huang Yanyu , Guo Feng , Li Tao , Yang Boning , Luo Deyan , Sun Yakun , Li Zhan , Wang Jianxin , He Zhili , Cheng Shiwei , Zhang Xingxiao , Wang Hui
Published: May 2021

Human beta-defensins (hBDs) play an important role in the host defense against various microbes, showing different levels of antibacterial activity and salt resistance in vitro. It is of interest to investigate whether can chimeric hBD analogs enhanced antibacterial activity and salt resistance. In this study, we designed a chimeric human defensin, named H4, by combining sequences of human beta-defensin-3 (hBD-3) and human beta-defensin-4 (hBD-4), then evaluated its antibacterial activity, salt resistance, and cytotoxic effects. The result showed that the antibacterial activity of H4 against most tested strains, including Klebsiella pneumonia, Enterococcus faecalis, Staphyloccocus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, and Acinetobacter baumannii was significantly improved compared to that of hBD-3 and hBD-4. Notably, H4 exhibited significantly better antibacterial activity against multidrug resistant isolate A. baumannii MDR-ZJ06 than commonly used antibiotics. Chimeric H4 still showed more than 80% antibacterial activity at high salt concentration (150 μM), which proves its good salt tolerance. The cytotoxic effect assay showed that the toxicity of H4 to Hela, Vero, A549 cells and erythrocytes at a low dose (<10 μg/ml) was similar to that of hBD-3 and hBD-4. In conclusion, given its broad spectrum of antibacterial activity and high salt resistance, chimeric H4 could serve as a promising template for new therapeutic antimicrobial agents.
Heat Shock Protein A6, a Novel HSP70, Is Induced During Enterovirus A71 Infection to Facilitate Internal Ribosomal Entry Site-Mediated Translation
Authors: Su Yu-Siang , Hwang Lih-Hwa , Chen Chi-Ju
Published: May 2021

Enterovirus A71 (EV-A71) is a human pathogen causing hand, foot, and mouth disease (HFMD) in children. Its infection can lead to severe neurological diseases or even death in some cases. While being produced in a large quantity during infection, viral proteins often require the assistance from cellular chaperones for proper folding. In this study, we found that heat shock protein A6 (HSPA6), whose function in viral life cycle is scarcely studied, was induced and functioned as a positive regulator for EV-A71 infection. Depletion of HSPA6 led to the reductions of EV-A71 viral proteins, viral RNA and virions as a result of the downregulation of internal ribosomal entry site (IRES)-mediated translation. Unlike other HSP70 isoforms such as HSPA1, HSPA8, and HSPA9, which regulate all phases of the EV-A71 life, HSPA6 was required for the IRES-mediated translation only. Unexpectedly, the importance of HSPA6 in the IRES activity could be observed in the absence of viral proteins, suggesting that HSPA6 facilitated IRES activity through cellular factor(s) instead of viral proteins. Intriguingly, the knockdown of HSPA6 also caused the reduction of luciferase activity driven by the IRES from coxsackievirus A16, echovirus 9, encephalomyocarditis virus, or hepatitis C virus, supporting that HSPA6 may assist the function of a cellular protein generally required for viral IRES activities.
Structure-Guided Computational Approaches to Unravel Druggable Proteomic Landscape of Mycobacterium leprae
Authors: Vedithi Sundeep Chaitanya , Malhotra Sony , Acebrón-García-de-Eulate Marta , Matusevicius Modestas , Torres Pedro Henrique Monteiro , Blundell Tom L.
Published: May 2021

Leprosy, caused by Mycobacterium leprae (M. leprae), is treated with a multidrug regimen comprising Dapsone, Rifampicin, and Clofazimine. These drugs exhibit bacteriostatic, bactericidal and anti-inflammatory properties, respectively, and control the dissemination of infection in the host. However, the current treatment is not cost-effective, does not favor patient compliance due to its long duration (12 months) and does not protect against the incumbent nerve damage, which is a severe leprosy complication. The chronic infectious peripheral neuropathy associated with the disease is primarily due to the bacterial components infiltrating the Schwann cells that protect neuronal axons, thereby inducing a demyelinating phenotype. There is a need to discover novel/repurposed drugs that can act as short duration and effective alternatives to the existing treatment regimens, preventing nerve damage and consequent disability associated with the disease. Mycobacterium leprae is an obligate pathogen resulting in experimental intractability to cultivate the bacillus in vitro and limiting drug discovery efforts to repositioning screens in mouse footpad models. The dearth of knowledge related to structural proteomics of M. leprae, coupled with emerging antimicrobial resistance to all the three drugs in the multidrug therapy, poses a need for concerted novel drug discovery efforts. A comprehensive understanding of the proteomic landscape of M. leprae is indispensable to unravel druggable targets that are essential for bacterial survival and predilection of human neuronal Schwann cells. Of the 1,614 protein-coding genes in the genome of M. leprae, only 17 protein structures are available in the Protein Data Bank. In this review, we discussed efforts made to model the proteome of M. leprae using a suite of software for protein modeling that has been developed in the Blundell laboratory. Precise template selection by employing sequence-structure homology recognition software, multi-template modeling of the monomeric models and accurate quality assessment are the hallmarks of the modeling process. Tools that map interfaces and enable building of homo-oligomers are discussed in the context of interface stability. Other software is described to determine the druggable proteome by using information related to the chokepoint analysis of the metabolic pathways, gene essentiality, homology to human proteins, functional sites, druggable pockets and fragment hotspot maps.
Molecular Characterization of Carbonic Anhydrase II (CA II) and Its Potential Involvement in Regulating Shell Formation in the Pacific Abalone, Haliotis discus hannai
Authors: Sharker Md. Rajib , Sukhan Zahid Parvez , Sumi Kanij Rukshana , Choi Sang Ki , Choi Kap Seong , Kho Kang Hee
Published: May 2021

Carbonic anhydrases (CAs) are a family of metalloenzymes that can catalyze the reversible interconversion of CO2/HCO3–, ubiquitously present in both prokaryotes and eukaryotes. In the present study, a CA II (designated as HdhCA II) was sequenced and characterized from the mantle tissue of the Pacific abalone. The complete sequence of HdhCA II was 1,169 bp, encoding a polypeptide of 349 amino acids with a NH2-terminal signal peptide and a CA architectural domain. The predicted protein shared 98.57% and 68.59% sequence identities with CA II of Haliotis gigantea and Haliotis tuberculata, respectively. Two putative N-linked glycosylation motifs and two cysteine residues could potentially form intramolecular disulfide bond present in HdhCA II. The phylogenetic analysis indicated that HdhCA II was placed in a gastropod clade and robustly clustered with CA II of H. gigantea and H. tuberculata. The highest level of HdhCA II mRNA expression was detected in the shell forming mantle tissue. During ontogenesis, the mRNA of HdhCA II was detected in all stages, with larval shell formation stage showing the highest expression level. The in situ hybridization results detected the HdhCA II mRNA expression in the epithelial cells of the dorsal mantle pallial, an area known to express genes involved in the formation of a nacreous layer in the shell. This is the first report of HdhCA II in the Pacific abalone, and the results of this study indicate that this gene might play a role in the shell formation of abalone.
Applications of Bacterial Degrons and Degraders — Toward Targeted Protein Degradation in Bacteria
Authors: Izert Matylda Anna , Klimecka Maria Magdalena , Górna Maria Wiktoria
Published: May 2021

A repertoire of proteolysis-targeting signals known as degrons is a necessary component of protein homeostasis in every living cell. In bacteria, degrons can be used in place of chemical genetics approaches to interrogate and control protein function. Here, we provide a comprehensive review of synthetic applications of degrons in targeted proteolysis in bacteria. We describe recent advances ranging from large screens employing tunable degradation systems and orthogonal degrons, to sophisticated tools and sensors for imaging. Based on the success of proteolysis-targeting chimeras as an emerging paradigm in cancer drug discovery, we discuss perspectives on using bacterial degraders for studying protein function and as novel antimicrobials.
Targeting Contrast Agents With Peak Near-Infrared-II (NIR-II) Fluorescence Emission for Non-invasive Real-Time Direct Visualization of Thrombosis
Authors: Hettie Kenneth S.
Published: May 2021

Thrombosis within the vasculature arises when pathological factors compromise normal hemostasis. On doing so, arterial thrombosis (AT) and venous thrombosis (VT) can lead to life-threatening cardio-cerebrovascular complications. Unfortunately, the therapeutic window following the onset of AT and VT is insufficient for effective treatment. As such, acute AT is the leading cause of heart attacks and constitutes ∼80% of stroke incidences, while acute VT can lead to fatal therapy complications. Early lesion detection, their accurate identification, and the subsequent appropriate treatment of thrombi can reduce the risk of thrombosis as well as its sequelae. As the success rate of therapy of fresh thrombi is higher than that of old thrombi, detection of the former and accurate identification of lesions as thrombi are of paramount importance. Magnetic resonance imaging, x-ray computed tomography (CT), and ultrasound (US) are the conventional non-invasive imaging modalities used for the detection and identification of AT and VT, but these modalities have the drawback of providing only image-delayed indirect visualization of only late stages of thrombi development. To overcome such limitations, near-infrared (NIR, ca. 700–1,700 nm) fluorescence (NIRF) imaging has been implemented due to its capability of providing non-invasive real-time direct visualization of biological structures and processes. Contrast agents designed for providing real-time direct or indirect visualization of thrombi using NIRF imaging primarily provide peak NIR-I fluorescence emission (ca. 700–1,000 nm), which affords limited tissue penetration depth and suboptimal spatiotemporal resolution. To facilitate the enhancement of the visualization of thrombosis via providing detection of smaller, fresh, and/or deep-seated thrombi in real time, the development of contrast agents with peak NIR-II fluorescence emission (ca. 1000–1,700 nm) has been recently underway. Currently, however, most contrast agents that provide peak NIR-II fluorescence emissions that are purportedly capable of providing direct visualization of thrombi or their resultant occlusions actually afford only the indirect visualization of such because they only provide for the (i) measuring of the surrounding vascular blood flow and/or (ii) simple tracing of the vasculature. These contrast agents do not target thrombi or occlusions. As such, this mini review summarizes the extremely limited number of targeting contrast agents with peak NIR-II fluorescence emission developed for non-invasive real-time direct visualization of thrombosis that have been recently reported.
SUMO: Glue or Solvent for Phase-Separated Ribonucleoprotein Complexes and Molecular Condensates?
Authors: Keiten-Schmitz Jan , Röder Linda , Hornstein Eran , Müller-McNicoll Michaela , Müller Stefan
Published: May 2021

Spatial organization of cellular processes in membranous or membrane-less organelles (MLOs, alias molecular condensates) is a key concept for compartmentalizing biochemical pathways. Prime examples of MLOs are the nucleolus, PML nuclear bodies, nuclear splicing speckles or cytosolic stress granules. They all represent distinct sub-cellular structures typically enriched in intrinsically disordered proteins and/or RNA and are formed in a process driven by liquid-liquid phase separation. Several MLOs are critically involved in proteostasis and their formation, disassembly and composition are highly sensitive to proteotoxic insults. Changes in the dynamics of MLOs are a major driver of cell dysfunction and disease. There is growing evidence that post-translational modifications are critically involved in controlling the dynamics and composition of MLOs and recent evidence supports an important role of the ubiquitin-like SUMO system in regulating both the assembly and disassembly of these structures. Here we will review our current understanding of SUMO function in MLO dynamics under both normal and pathological conditions.
Food Consumption and Characteristics Associated in a Brazilian Older Adult Population: A Cluster Analysis
Authors: Loureiro Laís M. R. , Almeida Luciene F. F. , Machado Carla J. , Pessoa Milene C. , Duarte Maria Sônia L. , Franceschini Sylvia C. C. , Ribeiro Andréia Q.
Published: May 2021

Epidemiological studies support diet as a factor in the prevention and treatment of non-communicable chronic diseases, whose occurrence increases with age due to the poor choices or the adoption of a monotonous diet. The aim of this study was to construct the food consumption profiles of older adults of a Brazilian city to identify the main food groups and eating habits that contribute to these profiles and to estimate its association with socioeconomic characteristics, health and use of health services, lifestyle, and anthropometric indicators. This is a population-based cross-sectional study conducted with a representative sample of 621 community-dwelling older adults (≥60 years) in Viçosa, Minas Gerais, Brazil. The food consumption profile was the dependent variable obtained from a Food Frequency Questionnaire, utilizing the two-step cluster method. The multiple multinomial logistic regression model was used to estimate the independent associations, obtaining the odds ratios and 95% confidence intervals. Three clusters were generated, namely, (1) “unhealthy” (2) “less unhealthy,” and (3) “fairly healthy.” The cluster “unhealthy” was characterized by a regular consumption of beans, fats, fatty/processed meats, and whole milk. The factors independently associated with this cluster were lower education level, lower individual income, history of at least one doctor's appointment in the year preceding this study, and being a former smoker. The cluster “less unhealthy” was characterized by a regular consumption of beans, green vegetables, vegetables and fruits, as well as fats, fatty/processed meats, and whole milk. The factors independently associated with the “less unhealthy” cluster were lower education level and history of at least six doctor's appointments in the prior year. The cluster “fairly healthy” was characterized by the same pattern of “less unhealthy,” except for skim milk and low-fat dairy products. The evidence of the associations indicates the profile of older adults who require greater attention and care related to improved nutrition. The illiterate or semi-literate aged individuals, those with low income, and those who neglect to seek medical advice must be the focus of healthy eating actions and programs.
Juvenile Selenium Deficiency Impairs Cognition, Sensorimotor Gating, and Energy Homeostasis in Mice
Authors: Kilonzo Victor W. , Sasuclark Alexandru R. , Torres Daniel J. , Coyle Celine , Pilat Jennifer M. , Williams Christopher S. , Pitts Matthew W.
Published: May 2021

Selenium (Se) is an essential micronutrient of critical importance to mammalian life. Its biological effects are primarily mediated via co-translational incorporation into selenoproteins, as the unique amino acid, selenocysteine. These proteins play fundamental roles in redox signaling and includes the glutathione peroxidases and thioredoxin reductases. Environmental distribution of Se varies considerably worldwide, with concomitant effects on Se status in humans and animals. Dietary Se intake within a narrow range optimizes the activity of Se-dependent antioxidant enzymes, whereas both Se-deficiency and Se-excess can adversely impact health. Se-deficiency affects a significant proportion of the world's population, with hypothyroidism, cardiomyopathy, reduced immunity, and impaired cognition being common symptoms. Although relatively less prevalent, Se-excess can also have detrimental consequences and has been implicated in promoting both metabolic and neurodegenerative disease in humans. Herein, we sought to comprehensively assess the developmental effects of both Se-deficiency and Se-excess on a battery of neurobehavioral and metabolic tests in mice. Se-deficiency elicited deficits in cognition, altered sensorimotor gating, and increased adiposity, while Se-excess was surprisingly beneficial.
A Deep Learning Model to Automate Skeletal Muscle Area Measurement on Computed Tomography Images
Authors: Amarasinghe Kaushalya C. , Lopes Jamie , Beraldo Julian , Kiss Nicole , Bucknell Nicholas , Everitt Sarah , Jackson Price , Litchfield Cassandra , Denehy Linda , Blyth Benjamin J. , Siva Shankar , MacManus Michael , Ball David , Li Jason , Hardcastle Nicholas
Published: May 2021

Background

Muscle wasting (Sarcopenia) is associated with poor outcomes in cancer patients. Early identification of sarcopenia can facilitate nutritional and exercise intervention. Cross-sectional skeletal muscle (SM) area at the third lumbar vertebra (L3) slice of a computed tomography (CT) image is increasingly used to assess body composition and calculate SM index (SMI), a validated surrogate marker for sarcopenia in cancer. Manual segmentation of SM requires multiple steps, which limits use in routine clinical practice. This project aims to develop an automatic method to segment L3 muscle in CT scans.

Methods

Attenuation correction CTs from full body PET-CT scans from patients enrolled in two prospective trials were used. The training set consisted of 66 non-small cell lung cancer (NSCLC) patients who underwent curative intent radiotherapy. An additional 42 NSCLC patients prescribed curative intent chemo-radiotherapy from a second trial were used for testing. Each patient had multiple CT scans taken at different time points prior to and post- treatment (147 CTs in the training and validation set and 116 CTs in the independent testing set). Skeletal muscle at L3 vertebra was manually segmented by two observers, according to the Alberta protocol to serve as ground truth labels. This included 40 images segmented by both observers to measure inter-observer variation. An ensemble of 2.5D fully convolutional neural networks (U-Nets) was used to perform the segmentation. The final layer of U-Net produced the binary classification of the pixels into muscle and non-muscle area. The model performance was calculated using Dice score and absolute percentage error (APE) in skeletal muscle area between manual and automated contours.

Results

We trained five 2.5D U-Nets using 5-fold cross validation and used them to predict the contours in the testing set. The model achieved a mean Dice score of 0.92 and an APE of 3.1% on the independent testing set. This was similar to inter-observer variation of 0.96 and 2.9% for mean Dice and APE respectively. We further quantified the performance of sarcopenia classification using computer generated skeletal muscle area. To meet a clinical diagnosis of sarcopenia based on Alberta protocol the model achieved a sensitivity of 84% and a specificity of 95%.

Conclusions

This work demonstrates an automated method for accurate and reproducible segmentation of skeletal muscle area at L3. This is an efficient tool for large scale or routine computation of skeletal muscle area in cancer patients which may have applications on low quality CTs acquired as part of PET/CT studies for staging and surveillance of patients with cancer.
Difference Between Signet Ring Cell Gastric Cancers and Non-Signet Ring Cell Gastric Cancers: A Systematic Review and Meta-Analysis
Authors: Zhang Chi , Liu Ran , Zhang Wei-Han , Chen Xin-Zu , Liu Kai , Yang Kun , Chen Xiao-Long , Zhao Lin-Yong , Chen Zhi-Xin , Zhou Zong-Guang , Hu Jian-Kun
Published: May 2021

Background:There is controversy about the characteristics and prognostic implications of signet ring cell gastric cancers and non-signet ring cell gastric cancers.

Objective:This study aims to evaluate clinicopathological characteristics and prognoses of signet ring cell carcinoma (SRCC) and non-signet ring cell carcinoma (NSRCC) of stomach.

Methods:Studies compared between SRCC and NSRCC of the stomach after gastrectomy and published before September 1st, 2020, in the PubMed, Cochrane, and Embase databases, were identified systematically.

Results:A total of 2,865 studies were screened, and 36 studies were included, with 19,174 patients in the SRCC group and 55,942 patients in the NSRCC group. SRCC patients were younger in age (P< 0.001), less likely to be male patients (P< 0.001), more afflicted with upper third lesions (P< 0.001), and presenting with more Borrmann type IV tumors (P= 0.005) than NSRCC patients. Lymph nodes metastasis was similar between SRCC and NSRCC patients with advanced tumor stage (OR: 0.86, 95% CI: 0.67–1.10,P= 0.23), but lower in the SRCC than NSRCC patients with early tumor stage (OR: 0.73; 95% CI: 0.56–0.98,P= 0.02). SRCC patients had comparable survival outcomes with NSRCC patients for early gastric cancers (HR: 1.05, 95% CI: 0.65–1.68,P< 0.001) but had significantly poor prognosis for patients with advanced tumor stage (HR: 1.50, 95% CI: 1.28–1.76,P< 0.001).

Conclusions:Signet ring cell carcinomas of the stomach are an increasingly common histopathological subtype of gastric cancers. These kinds of patients tend to be younger in age and more often female. Although, signet ring cell gastric cancer is a negative prognostic factor for patients with advanced stage. The difference is that for early stage of signet ring cell gastric cancers, it has low lymph nodes metastasis rate and comparable prognosis with non-signet ring cell cancers.
Integrated Analysis of Nine Prognostic RNA-Binding Proteins in Soft Tissue Sarcoma
Authors: Lin Lu-Lu , Liu Zi-Zhen , Tian Jing-Zhuo , Zhang Xiao , Zhang Yan , Yang Min , Zhong Hou-Cheng , Fang Wei , Wei Ren-Xiong , Hu Chao
Published: May 2021

RNA-binding proteins (RBPs) have been shown to be dysregulated in cancer transcription and translation, but few studies have investigated their mechanism of action in soft tissue sarcoma (STS). Here, The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to identify differentially expressed RBPs in STS and normal tissues. Through a series of biological information analyses, 329 differentially expressed RBPs were identified. Functional enrichment analysis showed that differentially expressed RBPs were mainly involved in RNA transport, RNA splicing, mRNA monitoring pathways, ribosome biogenesis and translation regulation. Through Cox regression analyses, 9 RBPs (BYSL, IGF2BP3, DNMT3B, TERT, CD3EAP, SRSF12, TLR7, TRIM21 and MEX3A) were all up-regulated in STS as prognosis-related genes, and a prognostic model was established. The model calculated a risk score based on the expression of 9 hub RBPs. The risk score could be used for risk stratification of patients and had a high prognostic value based on the receiver operating characteristic (ROC) curve. We also established a nomogram containing risk scores and 9 key RBPs to predict the 1-year, 3-year, and 5-year survival rates of patients in STS. Afterwards, methylation analysis showed significant changes in the methylation degree of BYSL, CD3EAP and MEX2A. Furthermore, the expression of 9 hub RBPs was closely related to immune infiltration rather than tumor purity. Based on the above studies, these findings may provide new insights into the pathogenesis of STS and will provide candidate biomarkers for the prognosis of STS.
Preoperative Serum Gamma-Glutamyltransferase as a Prognostic Biomarker in Patients Undergoing Radical Cystectomy for Bladder Cancer
Authors: Su Shiqiang , Liu Lizhe , Sun Chao , Nie Yanhua , Guo Hong , Hu Yang , Guo Shunli , Pang Shujian
Published: May 2021

Background

Serum gamma-glutamyltransferase (GGT) has been reported to be correlated with survival in a variety of malignancies. However, its effect on patients with bladder cancer (BC) treated by radical cystectomy has never been evaluated.

Patients and Methods

We retrospectively evaluated 263 patients who underwent radical surgery in our center. Baseline features, hematologic variables, and follow-up data were obtained. The endpoints included overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). The relationship between GGT and survival were evaluated.

Results

The median follow-up period for all patients was 34.7 (22.9-45.9) months. At the last follow-up, 67 patients died, 51 patients died of cancer, 92 patients experienced disease recurrence. Patients with an elevated serum GGT had a higher rate of pT3-T4 tumors. Patients with a higher preoperative serum GGT had a lower rate of OS, CSS and DFS (P < 0.001 for all). Multivariate analysis identified that preoperative serum GGT was independent predictor of OS (HR: 3.027, 95% CI: 1.716-5.338; P < 0.001), CSS (HR: 2.115, 95% CI: 1.093-4.090; P = 0.026), DFS (HR: 2.584, 95% CI: 1.569-4.255; P < 0.001). Age, diabetes history, pathologic T stage, and lymph node status also were independent predictors of prognosis for BC patients.

Conclusions

Our results indicated that preoperative serum GGT was an independent prognosis predictor for survival of BC patients after radical cystectomy, and can be included in the prognostic models.
The Prognostic Value of Non-Predominant Micropapillary Pattern in a Large Cohort of Resected Invasive Lung Adenocarcinoma Measuring ≤3 cm
Authors: Zhang Hua , Huang Wuhao , Liu Chang , Giaccone Giuseppe , Zhao Xiaoliang , Sun Xiaoyan , Li Jingjing , Cheng Runfen , Huang Qiujuan , Mo Huilan , Zhang Zhenfa , Zhang Bin , Wang Changli
Published: May 2021

The aim of this study was to analyze the influence of non-predominant micropapillary pattern in small sized invasive lung adenocarcinoma. A total of 986 lung adenocarcinoma patients with tumor size ≤3 cm were identified and classified according to the IALSC/ATS/ERS classification. Emphasis was placed on the impact of non-predominant micropapillary pattern on disease-free survival (DFS) and overall survival (OS). The relationship between lung adenocarcinoma subtype and lymph node involvement, EGFR mutation and KRAS mutation was also evaluated. A nomogram was developed to predict the probability of 3- and 5-year OS for these patients. The concordance index and calibration plot were used to validate this model. Among all 986 patients, the percentages of lymph node involvement were: 58.1, 50.0, 33.5, 21.4, 21.1, 10.9, 0, and 0% for micropapillary predominant, solid predominant, acinar predominant, papillary predominant, invasive mucinous adenocarcinoma (IMA), lepidic predominant, minimally invasive adenocarcinoma (MIA), adenocarcinoma in situ (AIS), respectively. The frequency of EGFR mutation in the cases of lepidic predominant, acinar predominant, MIA, micropapillary predominant, papillary predominant, solid predominant, IMA, and AIS were 51.1, 45.2, 44.4, 36.8, 29.3, 26.8, 8.3, and 0%, respectively. A non-predominant micropapillary pattern was observed in 344 (38.4%) invasive adenocarcinoma (IAC), and its presence predicted a poorer DFS (median: 56.0 months vs. 66.0 months, P <0.001) and OS (median: 61.0 months vs. 70.0 months, P <0.001). After propensity score matching, non-predominant micropapillary pattern retained its unfavorable effect on DFS (P = 0.007) and OS (P = 0.001). Multivariate analysis showed that non-predominant micropapillary pattern was identified as an independent prognostic factor for DFS (P = 0.003) and OS (P <0.001) in IAC. The nomogram showed good calibration and reliable discrimination ability (C-index = 0.775) to evaluated the 3- and 5-year OS. This retrospective analysis of patients with small sized IAC suggests the value of non-predominant micropapillary pattern to predict poor prognosis. A reliable nomogram model was constructed to provide personalized survival predictions.
Siteng Fang Reverses Multidrug Resistance in Gastric Cancer: A Network Pharmacology and Molecular Docking Study
Authors: Guo Lingjian , Shi Haixia , Zhu Limin
Published: May 2021

Siteng Fang (STF) has been shown to inhibit migration, invasion, and adhesion as well as promote apoptosis in gastric cancer (GC) cells. However, whether it can reverse the multidrug resistance (MDR) of GC to chemotherapy drugs is unknown. Thus, we aimed to elucidate the mechanism of STF in reversing the MDR of GC. The chemical composition of STF and genes related to GC were obtained from the TCMNPAS(TCM Network Pharmacology Analysis System, TCMNPAS) Database, and the targets of the active ingredients were predicted using the Swiss Target Prediction Database. The obtained data were mapped to obtain the key active ingredients and core targets of STF in treating GC. The active component-target network and protein interaction network were constructed by Cytoscape and String database, and the key genes and core active ingredients were obtained. The biological functions and related signal pathways corresponding to the key targets were analyzed and then verified via molecular docking. A total of 14 core active ingredients of STF were screened, as well as 20 corresponding targets, which were mainly enriched in cancer pathway, proteoglycan synthesis, PI3K-AKT signaling pathway, and focal adhesion. Molecular docking showed that the core active ingredients related to MDR, namely quercetin and diosgenin, could bind well to the target. In summary, STF may reverse the MDR of GC and exert synergistic effect with chemotherapeutic drugs. It mediates MDR mainly through the action of quercetin and diosgenin on the PI3K/AKT signaling pathway. These findings are the first to demonstrate the molecular mechanism of STF in reversing MDR in GC, thus providing a direction for follow-up basic research.
Standardized Diagnostics Including PET-CT Imaging, Bilateral Tonsillectomy and Neck Dissection Followed by Risk-Adapted Post-Operative Treatment Favoring Radio-Chemotherapy Improve Survival of Neck Squamous Cell Carcinoma of Unknown Primary Patients
Authors: Wichmann Gunnar , Willner Maria , Kuhnt Thomas , Kluge Regine , Gradistanac Tanja , Wald Theresa , Fest Sandra , Lordick Florian , Dietz Andreas , Wiegand Susanne , Zebralla Veit
Published: May 2021

Background

About five to 10% of cancers in the head and neck region are neck squamous cell carcinoma of unknown primary (NSCCUP). Their diagnosis and treatment are challenging given the risk of missing occult tumors and potential relapse. Recently, we described human papillomavirus (HPV)-related NSCCUP-patients (NSCCUP-P) as a subgroup with superior survival. However, standardized diagnostic workup, novel diagnostic procedures, decision-making in the multidisciplinary tumor board (MDTB) and multimodal therapy including surgery and post-operative radio-chemotherapy (PORCT) may also improve survival.

Methods

For assessing the impact of standardized diagnostic processes simultaneously established with the MDTB on outcome, we split our sample of 115 NSCCUP-P into two cohorts treated with curative intent from 1988 to 2006 (cohort 1; n = 53) and 2007 to 2018 (cohort 2; n = 62). We compared diagnostic processes and utilized treatment modalities applying Chi-square tests, and outcome by Kaplan–Meier plots and Cox regression.

Results

In cohort 2, the standardized processes (regular use of [18F]-FDG-PET-CT imaging followed by examination under anesthesia, EUA, bilateral tonsillectomy and neck dissection, ND, at least of the affected site) improved detection of primaries (P = 0.026) mostly located in the oropharynx (P = 0.001). From 66.0 to 87.1% increased ND frequency (P = 0.007) increased the detection of extracapsular extension of neck nodes (ECE+) forcing risk factor-adapted treatment by increased utilization of cisplatin-based PORCT that improved 5-years progression-free and overall survival from 60.4 and 45.3 to 67.7% (P = 0.411) and 66.1% (P = 0.025).

Conclusions

Standardized diagnostic workup followed by ND and risk-factor adapted therapy improves survival of NSCCUP-P.
The Current Landscape of Congenital Heart Surgery in Northern China: A Geographic and Population-Based Analysis
Authors: Su Zhanhao , Xiang Li , Liu Zeye , Wu Hao , Li Shoujun , Chen Huiwen , Zhang Hao
Published: May 2021

Background: Congenital heart disease (CHD) is the leading birth defect in China, and many patients require congenital heart surgery (CHS) to achieve optimal outcomes. However, the current landscape and population accessibility to specialist resources for CHS in China are unclear.

Methods: Care facilities performing CHS were identified from the 2018 white book of Chinese cardiovascular surgery and were categorized as full or limited facilities based on specialist capacity. Census-based population data and road data were obtained from administrative sources. Service area analysis of all facilities was performed to estimate geographic accessibility.

Results: Of 93 facilities in 14 provinces and municipalities in northern China, only 30.1% had full specialist capacity. The shortage of pediatric cardiologists and mechanical circulatory support was the primary limiting factor. In 2018, 61.3% of facilities performed <200 CHS cases, and 31.6% of all CHS cases (N = 30,921) were performed in limited facilities with substantially lower volume than full-capacity facilities (median value: 85.0 vs. 368.0). Beijing had a disproportionately higher CHS volume (367 cases per million population) than other provinces. Of all children under 5 in northern China, only 12.9% live within 30 km (a typical half-day visit) of the service areas of all facilities. Compared to children from the eastern region (31.4%), 71.8% of children from the central region and 70.2% of children from the western region needed to travel >180 km (a typical overnight visit) to receive care in full-capacity facilities.

Conclusions: Many facilities for CHS in northern China had limited specialist capacity, and many CHD patients received suboptimal surgical care. Policy measures should address the significant geographic disparities to receive high-quality surgical care among disadvantaged patients.
Close Association Between Platelet Biogenesis and Alveolarization of the Developing Lung
Authors: Chen Xueyu , Zhong Junyan , Han Dongshan , Yao Fang , Zhao Jie , Wagenaar Gerry. T. M. , Yang Chuanzhong , Walther Frans J.
Published: May 2021

Bronchopulmonary dysplasia (BPD) is a neonatal chronic lung disease characterized by an arrest in alveolar and vascular development. BPD is secondary to lung immaturity, ventilator-induced lung injury, and exposure to hyperoxia in extremely premature infants, leading to a lifelong impairment of lung function. Recent studies indicate that the lung plays an important role in platelet biogenesis. However, the dynamic change of platelet production during lung development and BPD pathogenesis remains to be elucidated. We investigated the dynamic change of platelet parameters in extremely premature infants during BPD development, and in newborn rats during their normal development from birth to adulthood. We further studied the effect of hyperoxia exposure on platelet production and concomitant pulmonary maldevelopment in an experimental BPD rat model induced by prolonged exposure to hyperoxia. We detected a physiological increase in platelet count from birth to 36 weeks postmenstrual age in extremely premature infants, but platelet counts in extremely premature infants who developed BPD were persistently lower than gestational age-matched controls. In line with clinical findings, exposure to hyperoxia significantly decreased the platelet count in neonatal rats. Lung morphometry analysis demonstrated that platelet counts stabilized with the completion of lung alveolarization in rats. Our findings indicate a close association between platelet biogenesis and alveolarization in the developing lung. This phenomenon might explain the reduced platelet count in extremely premature infants with BPD.
Clinical Observation of the Correlation Between Overactive Bladder and Atopic Constitution in Children
Authors: Zheng Yue , Zhang Zhou , Hou Ling , Wang Xiuli , Jiang Kailei , Zhang Shucheng , Du Yue
Published: May 2021

Objective: The present study aimed to analyze the risk factors correlated with overactive bladder (OAB), observe the effects of desloratadine in the treatment of OAB, and explore the correlation between OAB and atopic constitution in children.

Methods: Correlation and binary logistic regression analysis of the medical data from 447 children clinically diagnosed with OAB from June 2019 to June 2020 were conducted. The data included a history of urticaria, eczema, itchy skin, and allergic rhinitis or allergic cough. The OABSS scores before and after treatment with desloratadine were compared to evaluate the effectiveness of desloratadine for OAB.

Results: The risk factors for OAB in children included eczema, allergic rhinitis or allergic cough, itchy skin, and the levels of total blood IgE. Desloratadine was 96.5% effective in treating cases with risk factors including eczema, allergic rhinitis or allergic cough, and itchy skin. There existed statistical significance in the difference in OABSS scores before and after the treatment of desloratadine (P < 0.05).

Conclusion: OAB in children was correlated with atopic manifestations such as eczema, itchy skin, allergic rhinitis, or allergic cough. Desloratadine was safe and effective in the treatment of OAB in children with atopic manifestations.
Acquired Rectourethral and Rectovaginal Fistulas in Children: A Systematic Review
Authors: Huang Xinjie , Tan Sarah Siyin , Chen Yajun , Li Tian
Published: May 2021

Background:Acquired rectourethral (RUF) or rectovaginal fistulas (RVF) in children are rare conditions in pediatric surgery. Prior literature are retrospective studies and based on a small number of patients. The managements and outcomes vary widely across different studies. No standard or recommended management has been universally adopted. The goal was to systematically summarize different causes, provide an overlook of current clinical trend and to derive recommendation from the literature regarding the etiology, managements, and outcomes of pediatric acquired RUF and RVF.

Methods:PubMed, Embase, Cochrane databases were searched using terms: rectourethral fistula, recto-urethral fistula, urethrorectal fistula, urethro-rectal fistula, rectovaginal fistula. All studies were retrospective, in English, and included patients under the age of 18 years. Any series with congenital cases, adult (>18 years), <2 fistula cases less and obstetric related causes were excluded. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline was followed.

Results:Of the 531 records identified, 26 articles with 163 patients (63 RUF and 100RVF) were fully analyzed. Most RUF resulted from trauma, most RVF were from infection of HIV. About 92 patients underwent 1 of 3 categories of definitive repair, including transanal (4.3%), trans-sphincteric (48.9%), and transperineal (30.4%). Tissue interposition flaps were used in 37.6% patients, while temporary fecal diversions were used in 63.9% patients. Fistula was successfully closed in 50.3% patients (98.4% RUF and 20% RVF). 89.1 and 79.7 % of surgical repair patients had optimal fecal and urinary functions, respectively. In the inflammatory bowel disease and HIV infection related RVF patient group, the closure rate was prohibitive poor.

Conclusions:Most RVF are a sign of systematic diseases like HIV-infection or IBD and are associated with poor general conditions. While conservative treatment is recommended, stable patients can benefit from surgery. Further investigation is recommended if RVF are encountered without trauma or surgical history. RUF are likely to result from trauma or surgery, and transperineal or trans-sphincter approach can lead to closure and optimal function results. Fecal diversion and/or urinary diversion are helpful in some cases, while interposition technique may not be necessary. An objective scoring system for long-term follow-up and reporting consensus is needed to address treatment inconsistence.