bluuebunny/crossref_metadata_2025 huggingface dataset:
Broadening Predictive Understanding of Species’ Range Responses to Climate Change: The Case of Aloidendron dichotomum
Authors: Brodie Lara P. , Grey Kerry-Anne , Bishop Jacqueline M. , Midgley Guy F.
Published: October 2021

Concerns have been raised about attribution of species range shifts to anthropogenic climate change. Species paleo-range projections are emerging as a means to broaden understanding of range shifts and could be applied to assist in attribution. Apparent recent range contraction in the Quiver Tree (Aloidendron dichotomum (Masson) Klopper and Gideon F.Sm) has been attributed to anthropogenic climate change, but this has been challenged. We simulated the paleo- and future geographic range of A. dichotomum under changing climate using species distribution models (SDMs) to provide a broader perspective on its range dynamics. Ensemble modelling of the Last Glacial Maximum (LGM), mid-Holocene, current, and projected 2070 time periods simulates a paleo-historical poleward expansion of suitable bioclimatic space for this species under natural climate change post-LGM, and projects an eastward shift towards 2070. During the LGM, suitable bioclimatic space for A. dichotomum was simulated to be restricted to the equatorward part of its current range. During the Pleistocene/mid-Holocene climate transition period, the species’ range is predicted to have expanded significantly polewards at an average rate of 0.4 km per decade, assuming constant tracking of its optimal climatic niche. By 2070, suitable bioclimatic space is projected to expand further eastward into the summer rainfall region of South Africa, and contract in its equatorward reaches. Simulated post-LGM shifts roughly match expectations based on preliminary phylogenetic information, further supporting the attribution of current population declines to anthropogenic climate change drivers. Equatorward populations are required to migrate south-eastwards at a rate roughly 15 times faster than that calculated for the LGM/mid-Holocene climate transition period to avoid local extirpation. A preliminary analysis of range-wide genetic variation reveals a cline of variation, with generally higher levels in the central and more northerly part of the species distribution, as expected from the proposed paleo-range of the species. A more detailed analysis of the species’ phylogeographic history could be used to test the proposed paleo-range dynamics presented here, and if confirmed, would provide strong support for the use of this species as an indicator of anthropogenic climate change and a powerful case study for testing the implementation of conservation actions.
Variable Environments in an Upwelling System Trigger Differential Thermal Sensitivity in a Low Intertidal Chiton
Authors: Manríquez Nahomi , Bacigalupe Leonardo D. , Lardies Marco A.
Published: October 2021

Environmental variability in coastal oceans associated with upwelling dynamics probably is one of the most pervasive forces affecting the physiological performance of marine life. As the environmental temperature is the abiotic factor with major incidence in the physiology and ecology of marine ectotherms, the abrupt temperature changes in upwelling systems could generate important variations in these organisms’ functional processes. The relationship between ambient temperature and physiological performance can be described through a thermal performance curve (TPC). The parameters of this curve usually show geographic variation usually is in accordance with the predictions of the climate variability hypothesis (CVH), which states that organisms inhabiting more variable environments should have broader ranges of environmental tolerance in order to cope with the fluctuating environmental conditions they experience. Here we study the effect generated by the environmental variability in an active upwelling zone on the physiological performance of the marine ectotherm Achanthopleura echinata. In particular, we compared the parameters of the TPC and the metabolic rate of two populations of A. echinata, one found in high semi-permanent upwelling (Talcaruca), while the other is situated in an adjacent area with seasonal upwelling (Los Molles) and therefore more stable environmental conditions. Our results show that: (1) oxygen consumption increases with body size and this effect is more significant in individuals from the Talcaruca population, (2) optimal temperature, thermal breadth, upper critical limit and maximum performance were higher in the population located in the area of high environmental heterogeneity and (3) individuals from Talcaruca showed greater variance in optimal temperature, thermal breadth, upper critical limit but not in maximum performance. Although it is clear that a variable environment affects the thermal physiology of organisms, expanding their tolerance ranges and generating energy costs in the performance of individuals, it is relevant to note that upwelling systems are multifactorial phenomena where the rise of water masses modifies not only temperature, but also decreases O2, pH, and increases pCO2 which in turn could modify metabolism and TPC.
Development and Evaluation of a Fusion Polyprotein Based on HspX and Other Antigen Sequences for the Serodiagnosis of Tuberculosis
Authors: Zhou Fangbin , Xu Xindong , Cui Xiaobing , Pan Weiqing
Published: October 2021

Background

The lack of suitable diagnostic tools contributes to the high prevalence of tuberculosis (TB) worldwide. Serological tests, based on multiple target antigens, represent an attractive option for diagnosis of this disease due to their rapidity, convenience, and low cost.

Methods

Measures to reduce non-specific reactions and thereby improve the specificity of serological tests were investigated, including blocking antibodies against common bacteria in serum samples and synthesizing polypeptides covering non-conserved dominant B-cell epitopes of antigens. In addition, a fusion polyprotein containing HspX and eight other antigen sequences was constructed and expressed to increase overall sensitivity of the tests.

Results

Inclusion of Escherichia coli lysate partially increased the specificity of the serological tests, while synthesis and inclusion of peptides containing non-conserved sequences of TB antigens as well as dominant B-cell epitopes reduced non-specific reactions without a decrease in sensitivity of the tests. A polyprotein fusing HspX and eight other antigen sequences was constructed and displayed 60.2% sensitivity, which was higher than that of HspX and the other individual antigen segments. Moreover, the specificity of the polyprotein was 93.8%, which was not significantly decreased when compared with HspX and the other individual antigen segments.

Conclusions

The roles of the fusion polyprotein in the humoral immune response against TB infection were demonstrated and provide a potential novel approach for the development of TB diagnostics.
The Association Between Single-Nucleotide Polymorphisms of Co-Stimulatory Genes Within Non-HLA Region and the Prognosis of Leukemia Patients With Hematopoietic Stem Cell Transplantation
Authors: Chen Ding-Ping , Chang Su-Wei , Wang Po-Nan , Lin Wei-Tzu , Hsu Fang-Ping , Wang Wei-Ting , Tseng Ching-Ping
Published: October 2021

To avoid graft rejection, the hematopoietic stem cells with matched classical human leukocyte antigen (HLA) alleles are the primary choice for clinical allogeneic transplantation. However, even if the fully HLA-matched hematopoietic stem cells are used for transplantation, some patients still have poor prognosis after hematopoietic stem cell transplantation (HSCT), suggesting that the HLA system was not the only determinant of the outcomes of HSCT. In this study, we investigated whether the single-nucleotide polymorphisms (SNPs) of the co-stimulatory genes within non-HLA regions were related to the outcomes of HSCT. The genomic DNAs of 163 patients who had acute leukemia and received HSCT and their respective donors were collected for analysis. Thirty-four SNPs located in the four co-stimulatory genes including cytotoxic T-lymphocyte associated protein 4 (CTLA4), CD28, tumor necrosis factor ligand superfamily 4 (TNFSF4), and programmed cell death protein 1 (PDCD1) were selected to explore their relationship with the adverse outcomes after transplantation, including mortality, cytomegalovirus infection, graft-versus-host disease, and relapse. Our results revealed that nine SNPs in the CTLA4 gene, five SNPs in the PDCD1 gene, two SNPs in the TNFSF4 gene, and four SNPs in the CD28 gene were significantly associated with the occurrence of adverse outcomes post-HSCT. These SNPs may play important roles in immune response to allografts post-HSCT and can be the targets for developing strategy to identify appropriate donors.
Immunomic Investigation of Holocyclotoxins to Produce the First Protective Anti-Venom Vaccine Against the Australian Paralysis Tick, Ixodes holocyclus
Authors: Rodriguez-Valle Manuel , McAlister Sonia , Moolhuijzen Paula M. , Booth Mitchell , Agnew Kim , Ellenberger Claudia , Knowles Aleta G. , Vanhoff Kathleen , Bellgard Matthew I. , Tabor Ala E.
Published: October 2021

Venom producing animals are ubiquitously disseminated among vertebrates and invertebrates such as fish, snakes, scorpions, spiders, and ticks. Of the ~890 tick species worldwide, 27 have been confirmed to cause paralysis in mammalian hosts. The Australian paralysis tick (Ixodes holocyclus) is the most potent paralyzing tick species known. It is an indigenous three host tick species that secretes potent neurotoxins known as holocyclotoxins (HTs). Holocyclotoxins cause a severe and harmful toxicosis leading to a rapid flaccid paralysis which can result in death of susceptible hosts such as dogs. Antivenins are generally polyclonal antibody treatments developed in sheep, horses or camels to administer following bites from venomous creatures. Currently, the methods to prevent or treat tick paralysis relies upon chemical acaricide preventative treatments or prompt removal of all ticks attached to the host followed by the administration of a commercial tick-antiserum (TAS) respectively. However, these methods have several drawbacks such as poor efficacies, non-standardized dosages, adverse effects and are expensive to administer. Recently the I. holocyclus tick transcriptome from salivary glands and viscera reported a large family of 19 holocyclotoxins at 38-99% peptide sequence identities. A pilot trial demonstrated that correct folding of holocyclotoxins is needed to induce protection from paralysis. The immunogenicity of the holocyclotoxins were measured using commercial tick antiserum selecting HT2, HT4, HT8 and HT11 for inclusion into the novel cocktail vaccine. A further 4 HTs (HT1, HT12, HT14 and HT17) were added to the cocktail vaccine to ensure that the sequence variation among the HT protein family was encompassed in the formulation. A second trial comparing the cocktail of 8 HTs to a placebo group demonstrated complete protection from tick challenge. Here we report the first successful anti-venom vaccine protecting dogs from tick paralysis.
Breaking Bad: Autophagy Tweaks the Interplay Between Glioma and the Tumor Immune Microenvironment
Authors: Fan Yuxiang , Wang Yubo , Zhang Jian , Dong Xuechao , Gao Pu , Liu Kai , Ma Chengyuan , Zhao Gang
Published: October 2021

Though significant strides in tumorigenic comprehension and therapy modality have been witnessed over the past decades, glioma remains one of the most common and malignant brain tumors characterized by recurrence, dismal prognosis, and therapy resistance. Immunotherapy advance holds promise in glioma recently. However, the efficacy of immunotherapy varies among individuals with glioma, which drives researchers to consider the modest levels of immunity in the central nervous system, as well as the immunosuppressive tumor immune microenvironment (TIME). Considering the highly conserved property for sustaining energy homeostasis in mammalian cells and repeatedly reported links in malignancy and drug resistance, autophagy is determined as a cutting angle to elucidate the relations between glioma and the TIME. In this review, heterogeneity of TIME in glioma is outlined along with the reciprocal impacts between them. In addition, controversies on whether autophagy behaves cytoprotectively or cytotoxically in cancers are covered. How autophagy collapses from its homeostasis and aids glioma malignancy, which may depend on the cell type and the cellular context such as reactive oxygen species (ROS) and adenosine triphosphate (ATP) level, are briefly discussed. The consecutive application of autophagy inducers and inhibitors may improve the drug resistance in glioma after overtreatments. It also highlights that autophagy plays a pivotal part in modulating glioma and the TIME, respectively, and the intricate interactions among them. Specifically, autophagy is manipulated by either glioma or tumor-associated macrophages to conform one side to the other through exosomal microRNAs and thereby adjust the interactions. Given that some of the crosstalk between glioma and the TIME highly depend on the autophagy process or autophagic components, there are interconnections influenced by the status and well-being of cells presumably associated with autophagic flux. By updating the most recent knowledge concerning glioma and the TIME from an autophagic perspective enhances comprehension and inspires more applicable and effective strategies targeting TIME while harnessing autophagy collaboratively against cancer.
From Cellular Infiltration Assessment to a Functional Gene Set-Based Prognostic Model for Breast Cancer
Authors: Li Huamei , Huang Yiting , Sharma Amit , Ming Wenglong , Luo Kun , Gu Zhongze , Sun Xiao , Liu Hongde
Published: October 2021

Background

Cancer heterogeneity is a major challenge in clinical practice, and to some extent, the varying combinations of different cell types and their cross-talk with tumor cells that modulate the tumor microenvironment (TME) are thought to be responsible. Despite recent methodological advances in cancer, a reliable and robust model that could effectively investigate heterogeneity with direct prognostic/diagnostic clinical application remained elusive.

Results

To investigate cancer heterogeneity, we took advantage of single-cell transcriptome data and constructed the first indication- and cell type-specific reference gene expression profile (RGEP) for breast cancer (BC) that can accurately predict the cellular infiltration. By utilizing the BC-specific RGEP combined with a proven deconvolution model (LinDeconSeq), we were able to determine the intrinsic gene expression of 15 cell types in BC tissues. Besides identifying significant differences in cellular proportions between molecular subtypes, we also evaluated the varying degree of immune cell infiltration (basal-like subtype: highest; Her2 subtype: lowest) across all available TCGA-BRCA cohorts. By converting the cellular proportions into functional gene sets, we further developed a 24 functional gene set-based prognostic model that can effectively discriminate the overall survival (P = 5.9 × 10−33, n = 1091, TCGA-BRCA cohort) and therapeutic response (chemotherapy and immunotherapy) (P = 6.5 × 10−3, n = 348, IMvigor210 cohort) in the tumor patients.

Conclusions

Herein, we have developed a highly reliable BC-RGEP that adequately annotates different cell types and estimates the cellular infiltration. Of importance, the functional gene set-based prognostic model that we have introduced here showed a great ability to screen patients based on their therapeutic response. On a broader perspective, we provide a perspective to generate similar models in other cancer types to identify shared factors that drives cancer heterogeneity.
Spatiotemporal Variation in the Catch Composition and Abundance of Precious Corals Around Taiwan: Implications for Fisheries Management
Authors: Chen Chih-Shin
Published: October 2021

Precious corals are a fishery resource of cultural and religious importance. Because of their high commercial value, precious corals have been exploited for several centuries in the Mediterranean and for almost one century in the Northwest Pacific. Taiwanese fishing fleets have harvested precious corals since the 1920s; however, management regulations have only been promulgated since January 2009, when the catch and effort data of fisheries began to be collected. This study examined spatiotemporal variation in the catch composition and abundance of precious corals Corallium, Hemicorallium, and Pleurocorallium spp. around Taiwan using fishery data from 2009 to 2018 and discussed its implications for fisheries management. Licenses are issued for 60 vessels annually, and the annual total catch was 2.9–3.5 t between 2009 and 2018, peaking in 2015 and then decreasing sharply in 2016. Because of the use of non-selective fishing gear, dead and fossilized colonies were included in the total catches of the fishery. Fossilized colonies were predominant (average 78.5%) in the total catches, whereas the proportion of live colony catches accounted for less than 5%. Pink coral (Momo) was predominant in the total and live colony catches during the 10-year period. The Taiwanese precious coral fishing fleets are restricted to harvesting precious corals in five designated fishing grounds (DFGs; A–E). The fishing effort (vessel⋅day) was mainly concentrated in DFG-A (average 56.6%), which accounted for an average of 63.9% of the total catches. However, the live colony catches were largest in DFG-E (average 39.9%) and DFG-A (average 39.6%). The annual catch rates of live colonies decreased in two major fishing grounds (DFGs-A and DFG-B), whereas it increased in two minor fishing grounds (DFGs-C and DFG-D). The temporal variation in occurrence rates of live colonies decreased between 2015 and 2018, indicating a declining trend for precious coral populations around Taiwan. These results indicate that an unsustainable condition may occur in the near future if the precious corals continue to be harvested at the current scale. Revised regulations for the Taiwanese precious coral fishery should contain proposals on fishing gear modifications, a rotational harvesting scheme, or both; such measures can contribute to the conservation of precious coral populations. Regional cooperation in fisheries management is necessary to achieve the sustainable development of precious corals and their fisheries in the Northwest Pacific.
Perception of Dissolved Food-Related Compounds by the Sea Urchin Paracentrotus lividus (Echinodermata: Echinoidea)
Authors: Luis Orlando J. , Gago João M.
Published: October 2021

Echinoid feeding biology is well known but their sluggish responses to chemical stimuli have turned them into inadequately worked in the field of chemoreception. Echinoid responses to chemical stimulation had allowed, so far, only qualitative analyses based on tube-feet activity, directional, or masticatory movements, and artificial agarose foods. Besides stimulation through plumes of dissolved organic compounds and response analysis based on tube-feet activity, we propose another method to chemically stimulate echinoids that allows for fast and unambiguous responses and thus, quantitative analyses. Small squared pieces of absorbent semi-synthetic cleaning cloths, soaked with specific chemical compounds (simulacra), such as water insoluble lipid oils, were deposited singly or concurrently with a blank on the aboral hemisphere of each sea urchin, allowing choice and eventual transport down to the mouth by tube feet and spines of one or both cloths. The responsiveness ofParacentrotus lividuswas clearly dependent on its nutritional state. Well-fed sea urchins (maize whole grains) rarely responded, while the ones fed with less caloric rations (Kombu seaweed) responded faster and objectively. Stimulating sea urchinP. lividuswith 41 different food-related compounds, such as carbohydrates, proteins, peptides and amino acids, oils and fatty acids, and purified chemicals related with some human basic tastes, it was possible to evidence a clear ability of this echinoid species to positively discriminate proteins, starches, and a very few oils. Perceived as incitants/stimulants we have only found among proteins gliadin (from wheat gluten) but not casein (from bovine milk), among polysaccharides starch but not laminarin (from kelp) or glycogen (from mussels), and among lipids only the fatty acid linolenic acid. Among tissues, Kombu alga flesh and mussel flesh were readily perceived as both incitant/stimulant but not Kombu and mussel extracts. Therefore, the combined results reported here provide evidence forP. lividusas an omnivorous species rather than a strictly herbivorous marine species. However, the restricted group of food-related compounds perceived by this species as incitants or suppressants and as stimulants or deterrents was shown to be remarkably related to other vertebrates whose kinship was confirmed by the sequencing of the genome of another plant-eater sea urchin.
Key Bioturbator Species Within Benthic Communities Determine Sediment Resuspension Thresholds
Authors: de Smit Jaco C. , Brückner Muriel Z. M. , Mesdag Katherine I. , Kleinhans Maarten G. , Bouma Tjeerd J.
Published: October 2021

Abundant research has shown that macrobenthic species are able to increase sediment erodibility through bioturbation. So far, however, this has been at the level of individual species. Consequently, we lack understanding on how such species effects act on the level of bioturbator communities. We assessed the isolated and combined effects of three behaviorally contrasting macrobenthic species, i.e., Corophium volutator, Hediste diversicolor, and Limecola balthica, at varying densities on the critical bed shear stress for sediment resuspension (τcr). Overall, the effect of a single species on sediment erodibility could be described by a power function, indicating a relatively large effect of small bioturbator densities which diminishes toward higher individual density. In contrast to previous studies, our results could not be generalized between species using total metabolic rate, indicating that metabolic rate may be only suitable to integrate bioturbation effects within and between closely related species; highly contrasting species require consideration of species-specific bioturbation strategies. Experiments at the benthic community level revealed that the ability of a benthic community to reduce τcr is mainly determined by the species that has the largest individual effect in reducing τcr, as opposed to the species that is dominant in terms of metabolic rate. Hence, to predict and accurately model the net effect of bioturbator communities on the evolution of tidal flats and estuaries, identification of the key bioturbating species with largest effects on τcr and their spatial distribution is imperative. Metabolic laws may be used to describe their actual activity.
Association of Frailty With the Risk of Mortality and Resource Utilization in Elderly Patients in Intensive Care Units: A Meta-Analysis
Authors: Xia Feiping , Zhang Jing , Meng Shanshan , Qiu Haibo , Guo Fengmei
Published: October 2021

Background:The associations of frailty with the risk of mortality and resource utilization in the elderly patients admitted to intensive care unit (ICU) remain unclear. To address these issues, we performed a meta-analysis to determine whether frailty is associated with adverse outcomes and increased resource utilization in elderly patients admitted to the ICU.

Methods:We searched PubMed, EMBASE, ScienceDirect, and Cochrane Central Register of Controlled Trials through August 2021 to identify the relevant studies that investigated frailty in elderly (≥ 65 years old) patients admitted to an ICU and compared outcomes and resource utilization between frail and non-frail patients. The primary outcome was mortality. We also investigated the prevalence of frailty and the impact of frailty on the health resource utilization, such as hospital length of stay (LOS) and resource utilization of ICU.

Results:A total of 13 observational studies enrolling 64,279 participants (28,951 frail and 35,328 non-frail) were finally included. Frailty was associated with an increased risk of short-term mortality (10 studies, relative risk [RR]: 1.70; 95% CI: 1.45–1.98), in-hospital mortality (five studies, RR: 1.73; 95% CI: 1.55–1.93), and long-term mortality (six studies, RR: 1.86; 95% CI: 1.44–2.42). Subgroup analysis showed that retrospective studies identified a stronger correlation between frailty and hospital LOS (three studies, MD 1.14 d; 95% CI: 0.92–1.36).

Conclusions:Frailty is common in the elderly patients admitted to ICU, and is associated with increased mortality and prolonged hospital LOS.

Trial registration:This study was registered in the PROSPERO database (CRD42020207242).
Risk Factors of Invasive Fungal Infection in Recipients After Liver Transplantation: A Systematic Review and Meta-Analysis
Authors: Liu Min , Zhu Zhijun , Sun Liying
Published: October 2021

Objectives: Invasive fungal infection (IFI) remains an important cause of mortality in liver transplantation (LT). The objective of this meta-analysis was to identify the risk factors for IFI after LT.

Methods: We searched for relevant studies published up to June 2020 from PubMed, Web of Science, Embase, and the Cochrane Library. Odds ratios (ORs) and their corresponding 95% CIs were used to identify significant differences in the risk factors. Heterogeneity between studies was evaluated by the I2 test, and potential publication bias was assessed with Egger's test. The quality of included studies was evaluated with the Newcastle-Ottawa Scale (NOS).

Results: A total of 14 studies enrolling 4,284 recipients were included in the meta-analysis. Reoperation (OR = 2.18, 95% CI: 1.61–2.94), posttransplantation dialysis (OR = 2.03, 95% CI: 1.52–2.72), bacterial infection (OR = 1.81, 95% CI: 1.33–2.46), live donor (OR = 1.78, 95% CI: 1.20–2.63), retransplantation (OR = 2.45, 95% CI: 1.54–3.89), and fungal colonization (OR = 2.60, 95% CI: 1.99–3.42) were associated with the risk factors of IFI after LT.

Conclusions: Despite some risk factors that have been identified as significant factors for IFI post-LT, which may inform prevention recommendations, rigorous and well-designed studies with adequate sample sizes should be conducted to solve the limitations of this study.
Distinct Bile Acid Profiles in Patients With Chronic Hepatitis B Virus Infection Reveal Metabolic Interplay Between Host, Virus and Gut Microbiome
Authors: Sun Zeyu , Huang Chenjie , Shi Yixian , Wang Rusha , Fan Jun , Yu Ye , Zhang Zhehua , Zhu Kundan , Li Minwei , Ni Qin , Chen Zhi , Zheng Min , Yang Zhenggang
Published: October 2021

Hepatitis B virus (HBV) can hijack the host bile acids (BAs) metabolic pathway during infection in cell and animal models. Additionally, microbiome was known to play critical role in the enterohepatic cycle of BAs. However, the impact of HBV infection and associated gut microbiota on the BA metabolism in chronic hepatitis B (CHB) patients is unknown. This study aimed to unveil the distinct BA profiles in chronic HBV infection (CHB) patients with no or mild hepatic injury, and to explore the relationship between HBV, microbiome and BA metabolism with clinical implications.

Methods: Serum BA profiles were compared between CHB patients with normal ALT (CHB-NALT, n = 92), with abnormal ALT (CHB-AALT, n = 34) and healthy controls (HCs, n = 28) using UPLC-MS measurement. Hepatic gene expression in CHB patients were explored using previously published transcriptomic data. Fecal microbiome was compared between 30 CHB-NALT and 30 HCs using 16S rRNA sequencing, and key microbial function was predicted by PICRUSt analysis.

Results: Significant higher percentage of conjugated BAs and primary BAs was found in CHB patients even without apparent liver injury. Combinatory BA features can discriminate CHB patients and HCs with high accuracy (AUC = 0.838). Up-regulation of BA importer Na+ taurocholate co-transporting peptide (NTCP) and down-regulation of bile salt export pump (BSEP) was found in CHB-NALT patients. The microbial diversity and abundance of Lactobacillus, Clostridium, Bifidobacterium were lower in CHB-NALT patients compared to healthy controls. Suppressed microbial bile salt hydrolases (BSH), 7-alpha-hydroxysteroid dehydrogenase (hdhA) and 3-dehydro-bile acid Delta 4, 6-reductase (BaiN) activity were found in CHB-NALT patients.

Conclusion: This study provides new insight into the BA metabolism influenced both by HBV infection and associated gut microbiome modulations, and may lead to novel strategy for clinical management for chronic HBV infection.
Development and Verification of an Autophagy-Related lncRNA Signature to Predict Clinical Outcomes and Therapeutic Responses in Ovarian Cancer
Authors: Li Yan , Wang Juan , Wang Fang , Gao Chengzhen , Cao Yuanyuan , Wang Jianhua
Published: October 2021

Objective: Long noncoding RNAs (lncRNAs) are key regulators during ovarian cancer initiation and progression and are involved in mediating autophagy. In this study, we aimed to develop a prognostic autophagy-related lncRNA signature for ovarian cancer.

Methods: Autophagy-related abnormally expressed lncRNAs were screened in ovarian cancer with the criteria values of |correlation coefficient| > 0.4 and p < 0.001. Based on them, a prognostic lncRNA signature was established. The Kaplan–Meier overall survival analysis was conducted in high- and low-risk samples in the training, verification, and entire sets, followed by receiver operating characteristics (ROCs) of 7-year survival. Multivariate Cox regression analysis was used for assessing the predictive independency of this signature after adjusting other clinical features. The associations between the risk scores and immune cell infiltration, PD-L1 expression, and sensitivity of chemotherapy drugs were assessed in ovarian cancer.

Results: A total of 66 autophagy-related abnormally expressed lncRNAs were identified in ovarian cancer. An autophagy-related lncRNA signature was constructed for ovarian cancer. High-risk scores were indicative of poorer prognosis compared with the low-risk scores in the training, verification, and entire sets. ROCs of 7-year survival confirmed the well-predictive efficacy of this model. Following multivariate Cox regression analysis, this model was an independent prognostic factor. There were distinct differences in infiltrations of immune cells, PD-L1 expression, and sensitivity of chemotherapy drugs between high- and low-risk samples.

Conclusions: This study constructed an autophagy-related lncRNA signature that was capable of predicting clinical outcomes and also therapeutic responses for ovarian cancer.
The Involvement of Renal Capsule Is Associated With Acute Kidney Injury in Patients With Acute Pancreatitis
Authors: Wei Mei , Zhang Jingzhu , Qu Cheng , Liu Yang , Gao Kun , Zhou Jing , Ke Lu , Tong Zhihui , Li Weiqin , Li Jieshou
Published: October 2021

Background: Acute pancreatitis (AP) is characterized by pancreatic/peripancreatic inflammation. Involvement of renal capsule refers to peripancreatic inflammation extending beyond the Gerota fascia and disappearance of renal rim sign (+) on CT images. However, its association with acute kidney injury (AKI), an important complication of AP, was rarely studied.

Aim: This study aimed to assess the relationship between the involvement of renal capsule and AKI in a cohort of patients with AP.

Methods: We retrospectively screened all the patients admitted for AP from January 2018 to December 2019. The involvement of renal capsule was judged by experienced radiologists according to the CT imaging. Propensity score matching (PSM) was used to control for biases in group sizes and baseline characteristics. The primary outcome was the development of AKI during the index admission. We also categorized the pararenal inflammation with the renal rim grade (RRG) and compared the incidence of AKI among different grades.

Results: Involvement of renal capsule was identified in 71 of 503 patients (14.1%). The incidence of AKI was significantly higher in these patients when compared with the matched controls (43/71, 60.6% vs. 12/71, 16.9%, p < 0.001). Moreover, mortality also differed between groups (12.7% vs. 1.4%, p = 0.017). Multivariable logistic regression showed that renal capsule involvement is an independent risk factor of AKI (odds ratio, 4.355; 95% confidence interval, 1.434, 13.230, p = 0.009). Patients with RRG grade III had a significantly higher incidence of AKI than the other two grades (60.6% for Grade III, 17.1% for Grade II, and 3.8% for Grade I, p < 0.001).

Conclusion: Involvement of renal capsule is associated with higher AKI incidence and mortality.
The Impact of Normal Saline or Balanced Crystalloid on Plasma Chloride Concentration and Acute Kidney Injury in Patients With Predicted Severe Acute Pancreatitis: Protocol of a Phase II, Multicenter, Stepped-Wedge, Cluster-Randomized, Controlled Trial
Authors: Ye Bo , Huang Mingfeng , Chen Tao , Doig Gordon , Wu Bin , Chen Mingzhi , Tu Shumin , Chen Xiaomei , Yang Mei , Zhang Guoxiu , Li Qiang , Pan Xinting , Zhao Lijuan , Xia Honghai , Chen Yan , Ke Lu , Tong Zhihui , Bellomo Rinaldo , Windsor John , Li Weiqin
Published: October 2021

Introduction/aim: The supraphysiologic chloride concentration of normal saline may contribute to acute kidney injury (AKI). Balanced crystalloids can decrease chloride concentration and AKI in critically ill patients. We aim to test the hypothesis that, in patients with predicted severe acute pancreatitis (pSAP), compared with saline, fluid therapy with balanced crystalloids will decrease plasma chloride concentration.

Methods/Design: This is a multicenter, stepped-wedge, cluster-randomized, controlled trial. All eligible patients presenting to the 11 participating sites across China during the study period will be recruited. All sites will use saline for the first month and sequentially change to balanced crystalloids at the pre-determined and randomly allocated time point. The primary endpoint is the plasma chloride concentration on day 3 of enrollment. Secondary endpoints will include major adverse kidney events on hospital discharge or day 30 (MAKE 30) and free and alive days to day 30 for intensive care admission, invasive ventilation, vasopressors, and renal replacement therapy. Additional endpoints include daily serum chloride and sequential organ failure assessment (SOFA) score over the first seven days of enrollment.

Discussion: This study will provide data to define the impact of normal saline vs. balanced crystalloids on plasma chloride concentration and clinical outcomes in pSAP patients. It will also provide the necessary data to power future large-scale randomized trials relating to fluid therapy.

Ethics and Dissemination: This study was approved by the ethics committee of Jinling Hospital, Nanjing University (2020NZKY-015-01) and all the participating sites. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences.

Trial registration: The trial has been registered at the Chinese Clinical Trials Registry (ChiCTR2100044432).
Comparison of Transjugular Intrahepatic Portosystemic Shunt in the Treatment of Cirrhosis With or Without Portal Vein Thrombosis: A Retrospective Study
Authors: Wang Hong-Liang , Lu Wei-Jie , Zhang Yue-Lin , Nie Chun-Hui , Zhou Tan-Yang , Zhou Guan-Hui , Zhu Tong-Yin , Wang Bao-Quan , Chen Sheng-Qun , Yu Zi-Niu , Jing Li , Sun Jun-Hui
Published: October 2021

Aim: The purpose of our study was to conduct a retrospective analysis to compare the effectiveness of transjugular intrahepatic portosystemic shunts (TIPS) in the treatment of patients with cirrhosis with or without portal vein thrombosis (PVT).

Methods: We included a total of 203 cirrhosis patients successfully treated with TIPS between January 2015 and January 2018, including 72 cirrhosis patients with PVT (35.5%) and 131 without PVT (64.5%). Our subjects were followed for at least 1 year after treatment with TIPS. Data were collected to estimate the mortality, shunt dysfunction, and complication rates after TIPS creation.

Results: During the mean follow-up time of 19.5 ± 12.8 months, 21 (10.3%) patients died, 15 (7.4%) developed shunt dysfunction, and 44 (21.6%) experienced overt hepatic encephalopathy (OHE). No significant differences in mortality (P = 0.134), shunt dysfunction (P = 0.214), or OHE (P = 0.632) were noted between the groups. Age, model for end-stage liver disease (MELD) score, and refractory ascites requiring TIPS were risk factors for mortality. A history of diabetes, percutaneous transhepatic variceal embolization (PTVE), 8-mm diameter stent, and platelet (PLT) increased the risk of shunt dysfunction. The prevalence of variceal bleeding and recurrent ascites was comparable between the two groups (16.7 vs. 16.7% P = 0.998 and 2.7 vs. 3.8% P = 0.678, respectively).

Conclusions: Transjugular intrahepatic portosystemic shunts are feasible in the management of cirrhosis with PVT. No significant differences in survival or shunt dysfunction were noted between the PVT and no-PVT groups. The risk of recurrent variceal bleeding, recurrent ascites, and OHE in the PVT group was generally similar to that in the no-PVT group. TIPS represents a potentially feasible treatment option in cirrhosis patients with PVT.
Latent Diabetic Macular Edema in Chinese Diabetic Retinopathy Patients
Authors: Bai Xue , Hua Rui
Published: October 2021

Purpose: To compare the detection rates of optical coherence tomography (OCT) and fluorescein angiography (FA) in a diabetic macular edema (DME) and the severity of diabetic retinopathy in both color fundus images (CFI) and FA, and to investigate the predictive factors in macular leakages in FA.

Methods: This was a retrospective study, and a total of 132 eyes of 77 patients with diabetic retinopathy were enrolled. Macular OCT, FA, and CFI were reviewed and measured. Central foveal thickness was also measured.

Results: The severity of diabetic retinopathy in FA was significantly higher than that in CFI (p < 0.001). OCT detected 26 eyes with DMEs, which included the following: 13 eyes with cystoid macular edemas; 13 eyes with serous retinal detachments; 11 eyes with diffuse retinal thickening; 4 eyes with vitreomacular interface abnormalities. In contrast, 72 out of 132 eyes (54.5%) showed macular leakages in FA, which was significantly higher than that detected by OCT (p < 0.001). Compared with FA, the sensitivity and the specificity of OCT in detecting DMEs were 30.6 and 93.3%, respectively. However, central foveal thickness was not significantly different between the patients with non-clinically significant macular edema (CSME, 253.1 ± 26.95 μm) and slight CSME (270.9 ± 37.11 μm, p = 0.204). The mean central foveal thickness in diabetic macular edema (FA) eyes was 271.8 ± 66.02 μm, which was significantly higher than that (253. ± 25.21 μm) in non-DME (FA) eyes (p = 0.039). The central foveal thickness in DME (FA) eyes was significantly lower than that in eyes with DME (OCT) (p = 0.014). After adjusting for age and sex, a logistic regression analysis showed that the classification of diabetic retinopathy in FA was positively associated with macular leakage in FA (p < 0.001).

Conclusions: The severity of diabetic retinopathy is underestimated in CFI compared with that in FA. FA can detect latent DMEs, which appeared normal on OCT. The central foveal thickness is not a sensitive parameter for detecting latent DMEs.
TAFRO Syndrome in a Kidney Transplant Recipient That Was Diagnosed on Autopsy: A Case Report
Authors: Nagai Marie , Uchida Takahiro , Yamada Muneharu , Komatsu Shuuhei , Ota Kohei , Mukae Mitsuya , Iwamoto Hitoshi , Hirano Hiroshi , Karube Miho , Kaname Shinya , Oda Takashi
Published: October 2021

A 57-year-old man who received a kidney transplant 4 years previously owing to unknown underlying disease presented with thrombocytopenia and fever. Hepatosplenomegaly and lymphadenopathy were observed, and development of prominent anasarca and worsening of renal function yielded the diagnosis of TAFRO syndrome. He was treated with high-dose steroids and plasmapheresis, and a thrombopoietin receptor agonist was administered for refractory thrombocytopenia. However, his general condition worsened, and he died on day 92. Histopathological analysis of a kidney autopsy specimen showed thrombotic microangiopathy characterized by glomerular endothelial swelling, mesangiolysis, and double contours of the glomerular capillary walls. His bone marrow showed megakaryocytic hyperplasia with mild reticulin fibrosis. Interestingly, these clinical and pathological features were remarkably similar to those the patient demonstrated before the kidney transplant, suggesting the recurrence of TAFRO syndrome. TAFRO syndrome is a rare systemic disorder whose concept has recently been established, but information on its long-term outcome is scarce. To our knowledge, this is the first case of TAFRO syndrome developing in a kidney transplant recipient, which suggests that disease recurrence occurs many years after the kidney transplant.
Evaluating Viscoelastic Properties of the Wrist Joint During External Perturbations: Influence of Velocity, Grip, and Handedness
Authors: Falzarano Valeria , Holmes Michael W. R. , Masia Lorenzo , Morasso Pietro , Zenzeri Jacopo
Published: October 2021

In this study, we designed a robot-based method to compute a mechanical impedance model that could extract the viscoelastic properties of the wrist joint. Thirteen subjects participated in the experiment, testing both dominant and nondominant hands. Specifically, the robotic device delivered position-controlled disturbances in the flexion-extension degree of freedom of the wrist. The external perturbations were characterized by small amplitudes and fast velocities, causing rotation at the wrist joint. The viscoelastic characteristics of the mechanical impedance of the joint were evaluated from the wrist kinematics and corresponding torques. Since the protocol used position inputs to determine changes in mean wrist torque, a detailed analysis of wrist joint dynamics could be made. The scientific question was whether and how these mechanical features changed with various grip demands and perturbation velocities. Nine experimental conditions were tested for each hand, given by the combination of three velocity perturbations (fast, medium, and slow) and three hand grip conditions [self-selected grip, medium and high grip force, as percentage of the maximum voluntary contraction (MVC)]. Throughout the experiments, electromyographic signals of the extensor carpi radialis (ECR) and the flexor carpi radialis (FCR) were recorded. The novelty of this work included a custom-made soft grip sensor, wrapped around the robotic handle, to accurately quantify the grip force exerted by the subjects during experimentation. Damping parameters were in the range of measurements from prior studies and consistent among the different experimental conditions. Stiffness was independent of both direction and velocity of perturbations and increased with increasing grip demand. Both damping and stiffness were not different between the dominant and nondominant hands. These results are crucial to improving our knowledge of the mechanical characteristics of the wrist, and how grip demands influence these properties. This study is the foundation for future work on how mechanical characteristics of the wrist are affected in pathological conditions.
Antioxidant Vitamins and Carotenoids Intake and the Association With Poor Semen Quality: A Cross-Sectional Analysis of Men Referring to an Italian Fertility Clinic
Authors: De Cosmi Valentina , Parazzini Fabio , Agostoni Carlo , Noli Stefania , Cipriani Sonia , La Vecchia Irene , Ferrari Stefania , Esposito Giovanna , Bravi Francesca , Ricci Elena
Published: October 2021

Several studies suggested that male's diet affects fertility. This cross-sectional analysis from a prospective cohort study aims to explore the relation between antioxidants intake and sperm parameters in sub-fertile couples referring to a Fertility center. Socio-demographic characteristics, health history, lifestyle habits, and diet information were obtained. A semen sample was analyzed to proceed with assisted reproduction. Three hundred and twenty-three men were enrolled: 19.1% had semen volume (SV) < 1.5 mL, 31.4% sperm concentration (SC) < 15.0 mil/mL, 26.8% sperm motility < 32%, and 33.0% had total sperm count (TSC) < 39.0 mil. Higher levels of α-carotene were associated to lower risk of low SC [4th vs. 1st quartile, adjusted OR (aOR) 0.43, 95% CI 0.20–0.91) and low TSC (aOR 0.46, 95% CI 0.22–0.95). Higher intake of β-carotene was inversely associated with risk of low TSC. Lycopene intake was associated with higher risk for these conditions (aOR 2.46, 95%CI 1.01–5.98, SC), and (aOR 3.11, 95%CI 1.29–7.50, TSC). Risk of low semen volume was lower in men with higher level of vitamin D intake (aOR 0.25, 95%CI 0.09–0.66)]. Further research, especially, well-designed randomized clinical trials (RCT), is needed to understand how diet modifications may have a role in modulating male fertility and fecundability.
In vitro Digestion and Swelling Kinetics of Thymoquinone-Loaded Pickering Emulsions Incorporated in Alginate-Chitosan Hydrogel Beads
Authors: Wong See Kiat , Lawrencia Dora , Supramaniam Janarthanan , Goh Bey Hing , Manickam Sivakumar , Wong Tin Wui , Pang Cheng Heng , Tang Siah Ying
Published: October 2021

The present work aimed to investigate the swelling behavior, in vitro digestion, and release of a hydrophobic bioactive compound, thymoquinone (TQ), loaded in Pickering emulsion incorporated in alginate-chitosan hydrogel beads using a simulated gastrointestinal model. In this study, oil-in-water Pickering emulsions of uniform micron droplet sizes were formulated using 20% red palm olein and 0.5% (w/v) cellulose nanocrystals-soy protein isolate (CNC/SPI) complex followed by encapsulation within beads. FT-IR was used to characterize the bonding between the alginate, chitosan, and Pickering emulsion. 2% (w/v) alginate-1% (w/v) chitosan hydrogel beads were found to be spherical with higher stability against structural deformation. The alginate-chitosan beads displayed excellent stability in simulated gastric fluid (SGF) with a low water uptake of ~19%. The hydrogel beads demonstrated a high swelling degree (85%) with a superior water uptake capacity of ~593% during intestinal digestion in simulated intestinal fluid (SIF). After exposure to SIF, the microstructure transformation was observed, causing erosion and degradation of alginate/chitosan wall materials. The release profile of TQ up to 83% was achieved in intestinal digestion, and the release behavior was dominated by diffusion via the bead swelling process. These results provided useful insight into the design of food-grade colloidal delivery systems using protein-polysaccharide complex-stabilized Pickering emulsions incorporated in alginate-chitosan hydrogel beads.