bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicenter Study of Controlling Nutritional Status (CONUT) Score as a Prognostic Factor in Patients With HIV-Related Renal Cell Carcinoma
Authors: Xue Wenrui , Zhang Yu , Wang Hua , Zhang Yu , Hu Xiaopeng
Published: December 2021

Objective

In recent years, the controlled nutritional status (CONUT) score has been widely recognized as a new indicator for assessing survival in patients with urological neoplasms, including renal, ureteral, and bladder cancer. However, the CONUT score has not been analyzed in patients with HIV-related urological neoplasms. Therefore, we aimed to evaluate the prognostic significance of the CONUT score in patients with HIV-related renal cell carcinoma (RCC).

Methods

A total of 106 patients with HIV-related RCC were recruited from four hospitals between 2012 and 2021, and all included patients received radical nephrectomy or partial nephrectomy. The CONUT score was calculated by serum albumin, total lymphocyte counts, and total cholesterol concentrations. Patients with RCC were divided into two groups according to the optimal cutoff value of the CONUT score. Survival analysis of different CONUT groups was performed by the Kaplan–Meier method and a log rank test. A Cox proportional risk model was used to test for correlations between clinical variables and cancer-specific survival (CSS), overall survival (OS), and disease-free survival (DFS). Clinical variables included age, sex, hypertension, diabetes, tumor grade, Fuhrman grade, histology, surgery, and CD4+ T lymphocyte count.

Result

The median age was 51 years, with 93 males and 13 females. At a median follow-up of 41 months, 25 patients (23.6%) had died or had tumor recurrence and metastasis. The optimal cutoff value for the CONUT score was 3, and a lower CONUT score was associated with the Fuhrman grade (P=0.024). Patients with lower CONUT scores had better CSS (HR 0.197, 95% CI 0.077-0.502, P=0.001), OS (HR 0.177, 95% CI 0.070-0.446, P<0.001) and DFS (HR 0.176, 95% CI 0.070-0.444, P<0.001). Multivariate Cox regression analysis indicated that a low CONUT score was an independent predictor of CSS, OS and DFS (CSS: HR=0.225, 95% CI 0.067-0.749, P=0.015; OS: HR=0.201, 95% CI 0.061-0.661, P=0.008; DFS: HR=0.227, 95% CI 0.078-0.664, P=0.007). In addition, a low Fuhrman grade was an independent predictor of CSS (HR 0.192, 95% CI 0.045-0.810, P=0.025), OS (HR 0.203, 95% CI 0.049-0.842, P=0.028), and DFS (HR 0.180, 95% CI 0.048-0.669, P=0.010), while other factors, such as age, sex, hypertension, diabetes, tumor grade, histology, surgery, and CD4+ T lymphocyte count, were not associated with survival outcome.

Conclusion

The CONUT score, an easily measurable immune-nutritional biomarker, may provide useful prognostic information in HIV-related RCC.
Molecular and Cellular Heterogeneity in Rheumatoid Arthritis: Mechanisms and Clinical Implications
Authors: Zhao Jianan , Guo Shicheng , Schrodi Steven J. , He Dongyi
Published: December 2021

Rheumatoid arthritis is an autoimmune disease that exhibits significant clinical heterogeneity. There are various treatments for rheumatoid arthritis, including disease-modifying anti-rheumatic drugs (DMARDs), glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), and inflammatory cytokine inhibitors (ICI), typically associated with differentiated clinical effects and characteristics. Personalized responsiveness is observed to the standard treatment due to the pathophysiological heterogeneity in rheumatoid arthritis, resulting in an overall poor prognosis. Understanding the role of individual variation in cellular and molecular mechanisms related to rheumatoid arthritis will considerably improve clinical care and patient outcomes. In this review, we discuss the source of pathophysiological heterogeneity derived from genetic, molecular, and cellular heterogeneity and their possible impact on precision medicine and personalized treatment of rheumatoid arthritis. We provide emphasized description of the heterogeneity derived from mast cells, monocyte cell, macrophage fibroblast-like synoviocytes and, interactions within immune cells and with inflammatory cytokines, as well as the potential as a new therapeutic target to develop a novel treatment approach. Finally, we summarize the latest clinical trials of treatment options for rheumatoid arthritis and provide a suggestive framework for implementing preclinical and clinical experimental results into clinical practice.
How Times Have Changed! A Cornucopia of Antigens for Membranous Nephropathy
Authors: Caza Tiffany N. , Al-Rabadi Laith F. , Beck Laurence H.
Published: December 2021

The identification of the major target antigen phospholipase A2 receptor (PLA2R) in the majority of primary (idiopathic) cases of membranous nephropathy (MN) has been followed by the rapid identification of numerous minor antigens that appear to define phenotypically distinct forms of disease. This article serves to review all the known antigens that have been shown to localize to subepithelial deposits in MN, as well as the distinctive characteristics associated with each subtype of MN. We will also shed light on the novel proteomic approaches that have allowed identification of the most recent antigens. The paradigm of an antigen normally expressed on the podocyte cell surface leading toin-situimmune complex formation, complement activation, and subsequent podocyte injury will be discussed and challenged in light of the current repertoire of multiple MN antigens. Since disease phenotypes associated with each individual target antigens can often blur the distinction between primary and secondary disease, we encourage the use of antigen-based classification of membranous nephropathy.
Impact of Graft-Resident Leucocytes on Treg Mediated Skin Graft Survival
Authors: Steiner Romy , Weijler Anna M. , Wekerle Thomas , Sprent Jonathan , Pilat Nina
Published: December 2021

The importance and exact role of graft-resident leucocytes (also referred to as passenger leucocytes) in transplantation is controversial as these cells have been reported to either initiate or retard graft rejection. T cell activation to allografts is mediatedviarecognition of intact or processed donor MHC molecules on antigen-presenting cells (APC) as well as through interaction with donor-derived extracellular vesicles. Reduction of graft-resident leucocytes before transplantation is a well-known approach for prolonging organ survival without interfering with the recipient’s immune system. As previously shown by our group, injecting mice with IL-2/anti-IL-2 complexes (IL-2cplx) to augment expansion of CD4 T regulatory cells (Tregs) induces tolerance towards islet allografts, and also to skin allografts when IL-2cplx treatment is supplemented with rapamycin and a short-term treatment of anti-IL-6. In this study, we investigated the mechanisms by which graft-resident leucocytes impact graft survival by studying the combined effects of IL-2cplx-mediated Treg expansion and passenger leucocyte depletion. For the latter, effective depletion of APC and T cells within the graft was induced by prior total body irradiation (TBI) of the graft donor. Surprisingly, substantial depletion of donor-derived leucocytes by TBI did not prolong graft survival in naïve mice, although it did result in augmented recipient leucocyte graft infiltration, presumably through irradiation-induced nonspecific inflammation. Notably, treatment with the IL-2cplx protocol prevented early inflammation of irradiated grafts, which correlated with an influx of Tregs into the grafts. This finding suggested there might be a synergistic effect of Treg expansion and graft-resident leucocyte depletion. In support of this idea, significant prolongation of skin graft survival was achieved if we combined graft-resident leucocyte depletion with the IL-2cplx protocol; this finding correlated along with a progressive shift in the composition of T cells subsets in the grafts towards a more tolerogenic environment. Donor-specific humoral responses remained unchanged, indicating minor importance of graft-resident leucocytes in anti-donor antibody development. These results demonstrate the importance of donor-derived leucocytes as well as Tregs in allograft survival, which might give rise to new clinical approaches.
Increased Coral Larval Supply Enhances Recruitment for Coral and Fish Habitat Restoration
Authors: Harrison Peter L. , dela Cruz Dexter W. , Cameron Kerry A. , Cabaitan Patrick C.
Published: December 2021

Loss of foundation reef-corals is eroding the viability of reef communities and ecosystem function in many regions globally. Coral populations are naturally resilient but when breeding corals decline, larval supply becomes limiting and natural recruitment is insufficient for maintaining or restoring depleted populations. Passive management approaches are important but in some regions they are proving inadequate for protecting reefs, therefore active additional intervention and effective coral restoration techniques are needed. Coral spawning events produce trillions of embryos that can be used for mass larval rearing and settlement on degraded but recoverable reef areas. We supplied 4.6 million Acropora tenuis larvae contained in fine mesh enclosures in situ on three degraded reef plots in the northwestern Philippines during a five day settlement period to initiate restoration. Initial mean larval settlement was very high (210.2 ± 86.4 spat per tile) on natural coral skeleton settlement tiles in the larval-enhanced plots, whereas no larvae settled on tiles in control plots. High mortality occurred during early post-settlement life stages as expected, however, juvenile coral survivorship stabilised once colonies had grown into visible-sized recruits on the reef by 10 months. Most recruits survived and grew rapidly, resulting in significantly increased rates of coral recruitment and density in larval-enhanced plots. After two years growth, mean colony size reached 11.1 ± 0.61 cm mean diameter, and colonies larger than 13 cm mean diameter were gravid and spawned, the fastest growth to reproductive size recorded for broadcast spawning corals. After three years, mean colony size reached 17 ± 1.7 cm mean diameter, with a mean density of 5.7 ± 1.25 colonies per m–2, and most colonies were sexually reproductive. Coral cover increased significantly in larval plots compared with control plots, primarily from A. tenuis recruitment and growth. Total production cost for each of the 220 colonies within the restored breeding population after three years was United States $17.80 per colony. A small but significant increase in fish abundance occurred in larval plots in 2018, with higher abundance of pomacentrids and corallivore chaetodontids coinciding with growth of A. tenuis colonies. In addition, innovative techniques for capturing coral spawn slicks and larval culture in pools in situ were successfully developed that can be scaled-up for mass production of larvae on reefs in future. These results confirm that enhancing larval supply significantly increases settlement and coral recruitment on reefs, enabling rapid re-establishment of breeding coral populations and enhancing fish abundance, even on degraded reef areas.
Size Distribution, Length-Weight Relationship, and Size at Morphometric Maturity of the Mud Spiny Lobster Panulirus polyphagus (Herbst, 1793) in the Johor Strait
Authors: Waiho Khor , Fazhan Hanafiah , Shu-Chien Alexander Chong , Abualreesh Muyassar H. , Ma Hongyu , Syahnon Mohammad , Azmie Ghazali , Razman Nurul Jannah , Ikhwanuddin Mhd
Published: December 2021

Spiny lobsters of the genusPanulirusare economically important and support local fishing communities. However, mud spiny lobsterPanulirus polyphagusis among the least known species within this genus in terms of their biological information. This study relates to the size distribution, length-weight relationship, and size at morphometric maturity ofP. polyphagusin the Johor Strait. Within the year 2010, 300 specimens were collected off the coast of Johor Strait, Malaysia. There was no significant difference in body size (cephalothorax length, CL) and body weight (BW) between sexes. CL and BW were highly correlated and males ofP. polyphagusdisplayed positive growth allometry, whereas the opposite was observed in females. Based on the merus (ML) and carpus length (CPL) of the third right walking leg, the piecewise linear regression analysis estimated that the size at maturity for male was 6.58 cm CL (based on ML) and 7.58 cm CL (based on CPL), whereas it was 8.18 cm CL (based on ML) and 6.75 cm (based on CPL) for females. Two discriminant functions of high classification and revalidation rates (> 98.6% in males and > 98.7% in females) that can discern maturation status in males and females ofP. polyphaguswere derived using the discriminant function analysis. Biological information derived from this study serves as an essential baseline for future fishery management and conservation ofP. polyphagus.
Boldness Predicts Aggressiveness, Metabolism, and Activity in Black Rockfish Sebastes schlegelii
Authors: Fu Yiqiu , Zhang Zonghang , Zhang Zhen , Shen Fengyuan , Xu Xiuwen , Li Zheng , Zhang Yanhao , Zhang Xiumei
Published: December 2021

Animal personality refers to individual behavioral and physiological differences that are consistent over time and across context. Recently, the fish personality has gained increasing attention, especially from the perspective of aquaculture production. Here, we used an important aquaculture species, black rockfishSebastes schlegelii, as the target animal, and conducted a series of experiments to explore the relationships among fish boldness, aggressiveness, locomotor activity, opercular beat rate, standard metabolic rate, and cortisol level. Generally, the results showed that the boldness of black rockfish was significantly, positively correlated with fish aggressiveness, stressed locomotor activity, and standard metabolic rate, while was negatively correlated with stressed opercular beat rate. Bold fish had significantly higher aggressiveness, standard metabolic rate, and stressed locomotor activity but lower stressed opercular beat rate. However, there were no significant correlations between boldness and basal locomotor activity or between boldness and basal cortisol level. These results preliminarily constructed the behavioral and physiological spectrum of black rockfish in the context of fish personality and clearly indicated that the boldness could be used as a discrimination tool to predict fish aggressiveness and metabolic rate, which may have valuable applications for decreasing fish harmful aggression and increasing fish welfare in the aquaculture industry.
Changes in Growth Performance, Nutrient Metabolism, Antioxidant Defense and Immune Response After Fishmeal Was Replaced by Low-Gossypol Cottonseed Meal in Golden Pompano (Trachinotus ovatus)
Authors: Qin Yawen , He Chaoqun , Wang Wenqiang , Yang Peng , Wang Jun , Qin Qinbo , Mai Kangsen , Song Fei
Published: December 2021

The present study was designed to elucidate the changing pattern of growth performance, nutrient metabolism, antioxidant defense, and immune response after fishmeal (FM) was replaced by cottonseed meal (CSM). Four isonitrogenous and isolipidic experimental diets (42.5% crude protein, 14.0% crude lipid) were formulated to replace 0% (CSM0 diet), 20% (CSM20 diet), 40% (CSM40 diet), and 60% (CSM60 diet) of the FM protein with CSM. Juvenile golden pompano (Trachinotus ovatus) with an initial body weight of 24.8 ± 0.02 g were fed each diet for 6 weeks. The results showed that compared with the control diet, significant differences were not found in the weight gain ratio, specific growth performance, and apparent digestibility of dry matter and protein after 20% FM was replaced by CSM. Higher CSM replacement markedly decreased the growth performance (P < 0.05). Moreover, the CSM20 and CSM40 diets did not depress the feed efficiency ratio and protein efficiency ratio compared with the CSM0 diet. Further exploring the physio-biochemical and molecular responses, the present study also showed that dietary 20–40% CSM replacement had no significant effect on altering the whole body, plasma nutrient contents, free amino acids, or whole-body fatty acid contents. Additionally, the CSM20 diet did not change the mRNA and protein phosphorylation levels of the key enzymes and regulators involved in target of rapamycin (TOR) and amino acid response (AAR) signaling, nutrient metabolism, immune response, and antioxidant defense. Higher CSM inclusion significantly varied the TOR and AAR signaling response, nutrient metabolism, immune response, and antioxidant defense. Based on the results, CSM could successfully replace 20% FM in the formulated diets for golden pompano. This study proposes the optimal inclusion level of CSM in the diet, which has an important significance in optimizing aquafeeds formulation.
Relationship Between Cerebral Hemodynamics, Tissue Oxygen Saturation, and Delirium in Patients With Septic Shock: A Pilot Observational Cohort Study
Authors: Feng Qing , Ai Meilin , Huang Li , Peng Qianyi , Ai Yuhang , Zhang Lina
Published: December 2021

Background: Septic shock patients have tendencies toward impairment in cerebral autoregulation and imbalanced cerebral oxygen metabolism. Tissue Oxygen Saturation (StO2) and Transcranial Doppler (TCD) monitoring were undertaken to observe the variations of cerebral hemodynamic indices and cerebral/peripheral StO2 to find risk factors that increase the sepsis-associated delirium (SAD).

Materials and Methods: The research cohort was chosen from septic shock patients received in the Department of Critical Care Medicine, Xiangya Hospital, Central South University between May 2018 and March 2019. These patients were separated into two groups, SAD and non-SAD as assessed by using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Comparisons were made between the two groups in terms of peripheral StO2, fluctuations in regional cerebral oxygen saturation (rSO2), cerebral vascular automatic regulation function [Transient Hyperemic Response Ratio (THRR) index], cerebral hemodynamic index, organ function indicators, blood gas analysis indices, and patient characteristics.

Results: About 39% of the patients (20/51) suffered from SAD. Nearly 43% of the patients died within 28 days of admission (22/51). Individuals in the SAD cohort needed a longer period of mechanical ventilation [5 (95% CI 2, 6) vs. 1 days (95% CI 1, 4), p = 0.015] and more time in ICU [9 (95% CI 5, 20) vs. 5 days (95% CI 3, 9), p = 0.042]; they also experienced more deaths over the 28-day period (65 vs. 29%, p = 0.011). The multivariate regression analysis indicated that independent variables associated with SAD were THRR index [odds ratio (OR) = 5.770, 95% CI: 1.222–27.255; p = 0.027] and the mean value for rSO2 was < 55% (OR = 3.864, 95% CI: 1.026–14.550; p = 0.046).

Conclusion: Independent risk factors for SAD were mean cerebral oxygen saturation below 55% and cerebrovascular dysregulation (THRR < 1.09).
Case Reports: Bronchial Mucosal Vasculature Is Also Involved in the Acute Vascular Distress Syndrome of COVID-19
Authors: Jounieaux Vincent , Basille Damien , Toublanc Bénédicte , Andrejak Claire , Rodenstein Daniel Oscar , Mahjoub Yazine
Published: December 2021

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which targets the pulmonary vasculature is supposed to induce an intrapulmonary right to left shunt with an increased pulmonary blood flow. We report here what may be, to the best of our knowledge, the first videoendoscopic descriptions of an hypervascularization of the bronchial mucosa in two patients hospitalized for coronavirus disease 2019 (COVID-19) pneumonia.

Cases Presentation: Two patients, 27- and 37-year-old, were addressed to our Pneumology department for suspicion of COVID-19 pneumonia. Their symptoms (fever, dry cough, and dyspnoea), associated to pulmonary ground glass opacities on thoracic CT, were highly suggestive of a COVID-19 disease despite repeated negative pharyngeal swabs RT-PCR. In both patients, bronchoscopy examination using white light was unremarkable but NBI bronchoscopy revealed a diffuse hypervascularization of the mucosa from the trachea to the sub-segmental bronchi, associated with dilated submucosal vessels. RT-PCR performed in bronchoalveolar lavage (BAL) confirmed the presence of Sars-CoV-2.

Conclusions: These two case reports highlight the crucial importance of the vascular component of the viral disease. We suggest that such bronchial hypervascularization with dilated vessels contributes, at least in part, to the intrapulmonary right to left shunt that characterizes the COVID-19 related Acute Vascular Distress Syndrome (AVDS). The presence of diffuse bronchial hypervascularization in the context of COVID-19 pandemic should prompt the search for Sars-CoV-2 in BAL samples.
Poly(I:C)-Induced Mesenchymal Stem Cells Protect the Kidney Against Ischemia/Reperfusion Injury via the TLR3/PI3K Pathway
Authors: Chen Tian , Jiang Yamei , Xu Shihao , Cheuk Yin Celeste , Wang Jiyan , Yang Cheng , Rong Ruiming
Published: December 2021

Objective: To investigate the effect and protective mechanism of mesenchymal stem cell subpopulations on acute kidney injury by establishing a mouse model of renal ischemia-reperfusion injury.

Methods: Male C57BL/6 mice were randomly divided into five groups, namely, sham-operation group and those treated with normal saline, untreated mesenchymal stem cells, mesenchymal stem cells treated with lipopolysaccharide (LPS, pro-inflammatory phenotype) and mesenchymal stem cells treated with polyinosinic-polycytidylic acid (poly[I:C], anti-inflammatory phenotype) respectively. The renal function, histopathological damage, circulating inflammation levels and antioxidant capacity of mice were evaluated. The PI3 kinase p85 (PI3K) inhibitor was added into the conventional mesenchymal stem cell cultures in vitro to observe its effects on the secretion of anti-inflammatory cytokines.

Results: Mesenchymal stem cells treated with poly(I:C) (anti-inflammatory phenotype) could effectively reduce serum creatinine and blood urea nitrogen, attenuate histopathological damage and apoptosis level, decrease the level of circulating pro-inflammatory cytokines and increase the level of circulating anti-inflammatory cytokines, enhance peroxidase activity and reduce malondialdehyde content at each time point. After the addition of the PI3K inhibitor, the mRNA expression and protein secretion of indoleamine 2,3-dioxygenase 1 and heme oxygenase 1 of various mesenchymal stem cells were significantly reduced, and that of mesenchymal stem cells treated with poly(I:C) (anti-inflammatory phenotype) was more obvious.

Conclusions: Polyriboinosinic-polyribocytidylic acid (poly[I:C]), a synthetic double-stranded RNA, whose pretreatment induces mesenchymal stem cells to differentiate into the anti-inflammatory phenotype. Anti-inflammatory mesenchymal stem cells induced by poly(I:C) can better protect renal function, alleviate tissue damage, reduce circulating inflammation levels and enhance antioxidant capacity, and achieve stronger anti-inflammatory effects through the TLR3/PI3K pathway.
Development and Validation of a Deep Learning Algorithm to Automatic Detection of Pituitary Microadenoma From MRI
Authors: Li Qingling , Zhu Yanhua , Chen Minglin , Guo Ruomi , Hu Qingyong , Lu Yaxin , Deng Zhenghui , Deng Songqing , Zhang Tiecheng , Wen Huiquan , Gao Rong , Nie Yuanpeng , Li Haicheng , Chen Jianning , Shi Guojun , Shen Jun , Cheung Wai Wilson , Liu Zifeng , Guo Yulan , Chen Yanming
Published: December 2021

Background: It is often difficult to diagnose pituitary microadenoma (PM) by MRI alone, due to its relatively small size, variable anatomical structure, complex clinical symptoms, and signs among individuals. We develop and validate a deep learning -based system to diagnose PM from MRI.

Methods: A total of 11,935 infertility participants were initially recruited for this project. After applying the exclusion criteria, 1,520 participants (556 PM patients and 964 controls subjects) were included for further stratified into 3 non-overlapping cohorts. The data used for the training set were derived from a retrospective study, and in the validation dataset, prospective temporal and geographical validation set were adopted. A total of 780 participants were used for training, 195 participants for testing, and 545 participants were used to validate the diagnosis performance. The PM-computer-aided diagnosis (PM-CAD) system consists of two parts: pituitary region detection and PM diagnosis. The diagnosis performance of the PM-CAD system was measured using the receiver operating characteristics (ROC) curve and area under the ROC curve (AUC), calibration curve, accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1-score.

Results: Pituitary microadenoma-computer-aided diagnosis system showed 94.36% diagnostic accuracy and 98.13% AUC score in the testing dataset. We confirm the robustness and generalization of our PM-CAD system, the diagnostic accuracy in the internal dataset was 96.50% and in the external dataset was 92.26 and 92.36%, the AUC was 95.5, 94.7, and 93.7%, respectively. In human-computer competition, the diagnosis performance of our PM-CAD system was comparable to radiologists with >10 years of professional expertise (diagnosis accuracy of 94.0% vs. 95.0%, AUC of 95.6% vs. 95.0%). For the misdiagnosis cases from radiologists, our system showed a 100% accurate diagnosis. A browser-based software was designed to assist the PM diagnosis.

Conclusions: This is the first report showing that the PM-CAD system is a viable tool for detecting PM. Our results suggest that the PM-CAD system is applicable to radiology departments, especially in primary health care institutions.
Case Report: A Rare Case of Lupus Nephritis Associated With Mantle Cell Lymphoma
Authors: Bao Daorina , Tan Ying , Yu Xiaojuan , Wang Bingjie , Wang Hui , Xu Rong , Zhou Fude , Zhao Minghui
Published: December 2021

In this research, we described a very rare case of secondary lupus nephritis associated with B-cell lymphoma. An 84-year-old man was hospitalized at our institute for lower extremity edema persisting for over 2 months. He was diagnosed with systemic lupus erythematosus based on clinical and laboratory criteria, which showed impaired renal function and nephrotic syndrome with predominant hematuria. Renal biopsy showed IV+V lupus nephritis with highly infiltrated lymphoid cells in the kidney. Secondary lupus nephritis was suspected based on the possible pathogenesis of glomerular injury due to mantle cell lymphoma. Low-dose dexamethasone, rituximab, and lenalidomide were immediately started on the patient, and his renal function was improved after the first cycle of chemotherapy.
Trajectory of Estimated Glomerular Filtration Rate and Malnourishment Predict Mortality and Kidney Failure in Older Adults With Chronic Kidney Disease
Authors: Weng Shuo-Chun , Chen Chyong-Mei , Chen Yu-Chi , Wu Ming-Ju , Tarng Der-Cherng
Published: December 2021

Objective: The trajectory patterns of estimated glomerular filtration rates (eGFR) in chronic kidney disease (CKD) older adults with malnourishment and their association with subsequent patient outcomes have not been elucidated. We aimed to assess the eGFR trajectory patterns for predicting patient survival and kidney failure in the elderly without or with malnourishment.

Materials and Methods: Based on a prospective longitudinal cohort, CKD patients aged 65 years or older were enrolled from 2001 to 2013. Among the 3,948 patients whose eGFR trajectory patterns were analyzed, 1,872 patients were stratified by the absence or presence of malnourishment, and 765 patients were identified and categorized as having malnourishment. Four eGFR trajectory patterns [gradual decline (T0), early non-decline and then persistent decline (T1), persistent increase (T2), and low baseline and then progressive increase (T3)] were classified by utilizing a linear mixed-effect model with a quadratic term in time. The malnourishment was defined as body mass index < 22 kg/m2, serum albumin < 3.0 mg/dL, or Geriatric Nutritional Risk Index (GNRI) < 98. This study assessed the effectiveness of eGFR trajectory patterns in a median follow-up of 2.27 years for predicting all-cause mortality and kidney failure.

Results: The mean age was 76.9 ± 6.7 years, and a total of 82 (10.7%) patients with malnourishment and 57 (5.1%) patients without malnourishment died at the end of the study. Compared with the reference trajectory T0, the overall mortality of T1 was markedly reduced [adjusted hazard ratio (aHR) = 0.52, 95% confidence interval (CI) 0.32–0.83]. In patients with trajectory, T3 was associated with a high risk for kidney failure (aHR = 5.68, 95% CI 3.12–10.4) compared with the reference, especially higher risk in the presence of malnourishment. Patients with high GNRI values were significantly associated with a lower risk of death and kidney failure, but patients with malnourishment and concomitant alcohol consumption had a higher risk of kidney failure.

Conclusions: Low baseline eGFR and progressively increasing eGFR trajectory were high risks for kidney failure in CKD patients. These findings may be attributed to multimorbidity, malnourishment, and decompensation of renal function.
Artificial Intelligence to Detect Meibomian Gland Dysfunction From in-vivo Laser Confocal Microscopy
Authors: Zhang Ye-Ye , Zhao Hui , Lin Jin-Yan , Wu Shi-Nan , Liu Xi-Wang , Zhang Hong-Dan , Shao Yi , Yang Wei-Feng
Published: December 2021

Background: In recent years, deep learning has been widely used in a variety of ophthalmic diseases. As a common ophthalmic disease, meibomian gland dysfunction (MGD) has a unique phenotype in in-vivo laser confocal microscope imaging (VLCMI). The purpose of our study was to investigate a deep learning algorithm to differentiate and classify obstructive MGD (OMGD), atrophic MGD (AMGD) and normal groups.

Methods: In this study, a multi-layer deep convolution neural network (CNN) was trained using VLCMI from OMGD, AMGD and healthy subjects as verified by medical experts. The automatic differential diagnosis of OMGD, AMGD and healthy people was tested by comparing its image-based identification of each group with the medical expert diagnosis. The CNN was trained and validated with 4,985 and 1,663 VLCMI images, respectively. By using established enhancement techniques, 1,663 untrained VLCMI images were tested.

Results: In this study, we included 2,766 healthy control VLCMIs, 2,744 from OMGD and 2,801 from AMGD. Of the three models, differential diagnostic accuracy of the DenseNet169 CNN was highest at over 97%. The sensitivity and specificity of the DenseNet169 model for OMGD were 88.8 and 95.4%, respectively; and for AMGD 89.4 and 98.4%, respectively.

Conclusion: This study described a deep learning algorithm to automatically check and classify VLCMI images of MGD. By optimizing the algorithm, the classifier model displayed excellent accuracy. With further development, this model may become an effective tool for the differential diagnosis of MGD.
Butanol Purified Food Allergy Herbal Formula-2 Has an Immunomodulating Effect ex-vivo in Pediatric Crohn's Disease Subjects
Authors: Chen Xin , Lai Joanne , Song Ying , Yang Nan , Gnjatic Sacha , Gillespie Virginia , Hahn William , Chefitz Ezra , Pittman Nanci , Jossen Jacqueline , Benkov Keith , Dubinsky Marla , Li Xiu-Min , Dunkin David
Published: December 2021

Background: TNF-α has a major role in the pathogenesis of Crohn's disease (CD). In contrast, GM-CSF may be beneficial for its anti-inflammatory role in a subset of patients with CD with antibodies against GM-CSF as seen in prior trials of GM-CSF which resulted in clinical improvement in CD. We developed butanol purified Food Allergy Herbal Formula-2 (B-FAHF-2) by refining FAHF-2. FAHF-2 suppressed TNF-α production by human peripheral blood mononuclear cells (PBMCs) and colonic mucosa, and abrogated colitis in a murine model. We sought to examine the effect of B-FAHF-2 and the herbs that comprise it on TNF-α and GM-CSF production as a potential herbal therapy for the treatment of CD.

Methods: B-FAHF-2 was examined using high pressure liquid chromatography (HPLC) and compared to the original formulation, FAHF-2. PBMCs from pediatric patients with CD were cultured with lipopolysaccharide and B-FAHF-2, individual herbs or medium alone. Colonic biopsy specimens were cultured with or without B-FAHF-2. TNF-α and GM-CSF were measured by enzyme-linked immunosorbent assay (ELISA). B-FAHF-2 efficacy was tested in vivo in the CD45Rbhi transfer model.

Results: B-FAHF-2 had a similar HPLC fingerprint as FAHF-2 but decreased TNF-α production by PBMCs and colonic mucosa from pediatric CD subjects at 20% of the FAHF-2 dose. B-FAHF-2 increased GM-CSF production by PBMCs and colonic mucosa from pediatric CD subjects including those with antibodies to GM-CSF. Of B-FAHF-2's herbal constituents, only Huang Bai suppressed TNF-α and increased GM-CSF production. In the murine model, B-FAHF-2 treatment alleviated colitis.

Conclusions: B-FAHF-2 decreased TNF-α production by PBMCs and colonic mucosa from pediatric subjects at a lower dose than FAHF-2. B-FAHF-2 also increased GM-CSF production by PBMCs independent of antibodies. B-FAHF-2 may have a benefit in CD patients.
Case Report: Genomic Characteristics of the First Known Case of SARS-CoV-2 Imported From Spain to Sichuan, China
Authors: Liu Chao , Tang Bin , Gao Can , Deng Jianjun , Shen Min , Li Chaolin , Fu Zekun , Gao Zhan , Jiang Qi , Shi Hao , He Miao , Jiang Huaiwu , Jia Xu
Published: December 2021

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been basically under control in China since March 2020, but the import of domestic SARS-CoV-2 has begun to increase. This study reported the first case of asymptomatic SARS-CoV-2 infection imported from Spain into Sichuan Province, China, on March 11, 2020. The infected male had a body temperature of 37.5°C, normal blood oxygen saturation levels, and a computed tomography (CT) examination showed that his lungs had no shadows. However, a throat swab from the subject tested positive for SARS-CoV-2 using qPCR assay. In this study, we conducted transcriptome sequencing on respiratory throat swabs from the subject and found that the dominant SARS-CoV-2 sequence (Gene Bank ID: MW301121) was a spike protein D614G mutant strain, which is currently popular throughout world. We downloaded and analyzed SARS-CoV-2 sequences collected from cases in China and Spain for comparison and tracing purposes. After March 11, 2020, the Chinese domestic clade was naturally divided into the imported SARS-CoV-2 D614G mutant strain and evolutionarily-related similar sequences and that of sequences collected in the original Wuhan area. The sequence reported in this study was located on a small branch, far from the evolution of Wuhan sequences. As expected, the identified sequence was closely related to the evolution of the SARS-CoV-2 D614G mutant strain circulating in Spain.
In situ Prokaryotic and Eukaryotic Communities on Microplastic Particles in a Small Headwater Stream in Germany
Authors: Weig Alfons R. , Löder Martin G. J. , Ramsperger Anja F. R. M. , Laforsch Christian
Published: December 2021

The ubiquitous use of plastic products in our daily life is often accompanied by improper disposal. The first interactions of plastics with organisms in the environment occur by overgrowth or biofilm formation on the particle surface, which can facilitate the ingestion by animals. In order to elucidate the colonization of plastic particles by prokaryotic and eukaryotic microorganisms in situ, we investigated microbial communities in biofilms on four different polymer types and on mineral particles in a small headwater stream 500 m downstream of a wastewater treatment plant in Germany. Microplastic and mineral particles were exposed to the free-flowing water for 4 weeks in spring and in summer. The microbial composition of the developing biofilm was analyzed by 16S and 18S amplicon sequencing. Despite the expected seasonal differences in the microbial composition of pro- and eukaryotic communities, we repeatedly observed polymer type-specific differentiation in both seasons. The order of polymer type-specific prokaryotic and eukaryotic community distances calculated by Robust Aitchison principal component analysis (PCA) was the same in spring and summer samples. However, the magnitude of the distance differed considerably between polymer types. Prokaryotic communities on polyethylene particles exhibited the most considerable difference to other particles in summer, while eukaryotic communities on polypropylene particles showed the most considerable difference to other spring samples. The most contributing bacterial taxa to the polyethylene-specific differentiation belong to the Planctomycetales, Saccharimonadales, Bryobacterales, uncultured Acidiomicrobia, and Gemmatimonadales. The most remarkable differences in eukaryotic microorganism abundances could be observed in several distinct groups of Ciliophora (ciliates) and Chlorophytes (green algae). Prediction of community functions from taxonomic abundances revealed differences between spring and summer, and – to a lesser extent – also between polymer types and mineral surfaces. Our results show that different microplastic particles were colonized by different biofilm communities. These findings may be used for advanced experimental designs to investigate the role of microorganisms on the fate of microplastic particles in freshwater ecosystems.
Proteomic Analysis of a Syntrophic Coculture of Syntrophobacter fumaroxidans MPOBT and Geobacter sulfurreducens PCAT
Authors: Mollaei Monir , Suarez-Diez Maria , Sedano-Nunez Vicente T. , Boeren Sjef , Stams Alfons J. M. , Plugge Caroline M.
Published: December 2021

We established a syntrophic coculture of Syntrophobacter fumaroxidans MPOBT (SF) and Geobacter sulfurreducens PCAT (GS) growing on propionate and Fe(III). Neither of the bacteria was capable of growth on propionate and Fe(III) in pure culture. Propionate degradation by SF provides acetate, hydrogen, and/or formate that can be used as electron donors by GS with Fe(III) citrate as electron acceptor. Proteomic analyses of the SF-GS coculture revealed propionate conversion via the methylmalonyl-CoA (MMC) pathway by SF. The possibility of interspecies electron transfer (IET) via direct (DIET) and/or hydrogen/formate transfer (HFIT) was investigated by comparing the differential abundance of associated proteins in SF-GS coculture against (i) SF coculture with Methanospirillum hungatei (SF-MH), which relies on HFIT, (ii) GS pure culture growing on acetate, formate, hydrogen as propionate products, and Fe(III). We noted some evidence for DIET in the SF-GS coculture, i.e., GS in the coculture showed significantly lower abundance of uptake hydrogenase (43-fold) and formate dehydrogenase (45-fold) and significantly higher abundance of proteins related to acetate metabolism (i.e., GltA; 62-fold) compared to GS pure culture. Moreover, SF in the SF-GS coculture showed significantly lower abundance of IET-related formate dehydrogenases, Fdh3 (51-fold) and Fdh5 (29-fold), and the rate of propionate conversion in SF-GS was 8-fold lower than in the SF-MH coculture. In contrast, compared to GS pure culture, we found lower abundance of pilus-associated cytochrome OmcS (2-fold) and piliA (5-fold) in the SF-GS coculture that is suggested to be necessary for DIET. Furthermore, neither visible aggregates formed in the SF-GS coculture, nor the pili-E of SF (suggested as e-pili) were detected. These findings suggest that the IET mechanism is complex in the SF-GS coculture and can be mediated by several mechanisms rather than one discrete pathway. Our study can be further useful in understanding syntrophic propionate degradation in bioelectrochemical and anaerobic digestion systems.
Characterization of the MYB Genes Reveals Insights Into Their Evolutionary Conservation, Structural Diversity, and Functional Roles in Magnaporthe oryzae
Authors: Lee Sehee , Völz Ronny , Song Hyeunjeong , Harris William , Lee Yong-Hwan
Published: December 2021

The myeloblastosis (MYB) transcription factor family is evolutionarily conserved among plants, animals, and fungi, and contributes to their growth and development. We identified and analyzed 10 putative MYB genes in Magnaporthe oryzae (MoMYB) and determined their phylogenetic relationships, revealing high divergence and variability. Although MYB domains are generally defined by three tandem repeats, MoMYBs contain one or two weakly conserved repeats embedded in extensive disordered regions. We characterized the secondary domain organization, disordered segments, and functional contributions of each MoMYB. During infection, MoMYBs are distinctively expressed and can be subdivided into two clades of being either up- or down-regulated. Among these, MoMYB1 and MoMYB8 are up-regulated during infection and vegetative growth, respectively. We found MoMYB1 localized predominantly to the cytosol during the formation of infection structures. ΔMomyb1 exhibited reduced virulence on intact rice leaves corresponding to the diminished ability to form hypha-driven appressorium (HDA). We discovered that MoMYB1 regulates HDA formation on hard, hydrophobic surfaces, whereas host surfaces partially restored HDA formation in ΔMomyb1. Lipid droplet accumulation in hyphal tips and expression of HDA-associated genes were strongly perturbed in ΔMomyb1 indicating genetic interaction of MoMYB1 with downstream components critical to HDA formation. We also found that MoMYB8 is necessary for fungal growth, dark-induced melanization of hyphae, and involved in higher abiotic stress tolerance. Taken together, we revealed a multifaceted picture of the MoMYB family, wherein a low degree of conservation has led to the development of distinct structures and functions, ranging from fungal growth to virulence.
Microbial Electrochemical Fluidized Bed Reactor: A Promising Solution for Removing Pollutants From Pharmaceutical Industrial Wastewater
Authors: Asensio Yeray , Llorente María , Sánchez-Gómez Alejandro , Manchon Carlos , Boltes Karina , Esteve-Núñez Abraham
Published: December 2021

The capacity of electroactive bacteria to exchange electrons with electroconductive materials has been explored during the last two decades as part of a new field called electromicrobiology. Such microbial metabolism has been validated to enhance the bioremediation of wastewater pollutants. In contrast with standard materials like rods, plates, or felts made of graphite, we have explored the use of an alternative strategy using a fluid-like electrode as part of a microbial electrochemical fluidized bed reactor (ME-FBR). After verifying the low adsorption capacity of the pharmaceutical pollutants on the fluid-bed electrode [7.92 ± 0.05% carbamazepine (CBZ) and 9.42 ± 0.09% sulfamethoxazole (SMX)], our system showed a remarkable capacity to outperform classical solutions for removing pollutants (more than 80%) from the pharmaceutical industry like CBZ and SMX. Moreover, the ME-FBR performance revealed the impact of selecting an anode potential by efficiently removing both pollutants at + 200 mV. The high TOC removal efficiency also demonstrated that electrostimulation of electroactive bacteria in ME-FBR could overcome the expected microbial inhibition due to the presence of CBZ and SMX. Cyclic voltammograms revealed the successful electron transfer between microbial biofilm and the fluid-like electrode bed throughout the polarization tests. Finally, Vibrio fischeri-based ecotoxicity showed a 70% reduction after treating wastewater with a fluid-like anode (+ 400 mV), revealing the promising performance of this bioelectrochemical approach.
Polar Cryoconite Associated Microbiota Is Dominated by Hemispheric Specialist Genera
Authors: Millar Jasmin L. , Bagshaw Elizabeth A. , Edwards Arwyn , Poniecka Ewa A. , Jungblut Anne D.
Published: December 2021

Cryoconite holes, supraglacial depressions containing water and microbe-mineral aggregates, are known to be hotspots of microbial diversity on glacial surfaces. Cryoconite holes form in a variety of locations and conditions, which impacts both their structure and the community that inhabits them. Using high-throughput 16S and 18S rRNA gene sequencing, we have investigated the communities of a wide range of cryoconite holes from 15 locations across the Arctic and Antarctic. Around 24 bacterial and 11 eukaryotic first-rank phyla were observed in total. The various biotic niches (grazer, predator, photoautotroph, and chemotroph), are filled in every location. Significantly, there is a clear divide between the bacterial and microalgal communities of the Arctic and that of the Antarctic. We were able to determine the groups contributing to this difference and the family and genus level. Both polar regions contain a “core group” of bacteria that are present in the majority of cryoconite holes and each contribute >1% of total amplicon sequence variant (ASV) abundance. Whilst both groups contain Microbacteriaceae, the remaining members are specific to the core group of each polar region. Additionally, the microalgal communities of Arctic cryoconite holes are dominated by Chlamydomonas whereas the Antarctic cryoconite holes are dominated by Pleurastrum. Therefore cryoconite holes may be a global feature of glacier landscapes, but they are inhabited by regionally distinct microbial communities. Our results are consistent with the notion that cryoconite microbiomes are adapted to differing conditions within the cryosphere.
The Monte Carlo Simulation of Three Antimicrobials for Empiric Treatment of Adult Bloodstream Infections With Carbapenem-Resistant Enterobacterales in China
Authors: Zou Dongna , Yao Guangyue , Shen Chengwu , Ji Jinru , Ying Chaoqun , Wang Peipei , Liu Zhiying , Wang Jun , Jin Yan , Xiao Yonghong
Published: December 2021

Introduction: The aim of this study was to predict and evaluate three antimicrobials for treatment of adult bloodstream infections (BSI) with carbapenem-resistant Enterobacterales (CRE) in China, so as to optimize the clinical dosing regimen further.

Methods: Antimicrobial susceptibility data of blood isolates were obtained from the Blood Bacterial Resistance Investigation Collaborative Systems in China. Monte Carlo simulation was conducted to estimate the probability target attainment (PTA) and cumulative fraction of response (CFR) of tigecycline, polymyxin B, and ceftazidime/avibactam against CRE.

Results: For the results of PTAs, tigecycline following administration of 50 mg every 12 h, 75 mg every 12 h, and 100 mg every 12 h achieved > 90% PTAs when minimum inhibitory concentration (MIC) was 0.25, 0.5, and 0.5 μg/mL, respectively; polymyxin B following administration of all tested regimens achieved > 90% PTAs when MIC was 1 μg/mL with CRE; ceftazidime/avibactam following administration of 1.25 g every 8 h, 2.5 g every 8 h achieved > 90% PTAs when MIC was 4 μg/mL, 8 μg/mL with CRE, respectively. As for CFR values of three antimicrobials, ceftazidime/avibactam achieved the lowest CFR values. The highest CFR value of ceftazidime/avibactam was 77.42%. For tigecycline and ceftazidime/avibactam, with simulated regimens daily dosing increase, the CFR values were both increased; the highest CFR of tigecycline values was 91.88%. For polymyxin B, the most aggressive dosage of 1.5 mg/kg every 12 h could provide the highest CFR values (82.69%) against CRE.

Conclusion: This study suggested that measurement of MICs and individualized therapy should be considered together to achieve the optimal drug exposure. In particular, pharmacokinetic and pharmacodynamic modeling based on local antimicrobial resistance data can provide valuable guidance for clinicians for the administration of empirical antibiotic treatments for BSIs.