bluuebunny/crossref_metadata_2025 huggingface dataset:
The Problem with Using a Maxim Permissibility Test to Derive Obligations
Authors: Kahn Samuel
Published: June 2022

The purpose of this paper is to show that, if Kant’s universalization formulations of the Categorical Imperative are our only standards for judging right from wrong and permissible from impermissible, then we have no obligations. I shall do this by examining five different views of how obligations can be derived from the universalization formulations and arguing that each one fails. I shall argue that the first view rests on a misunderstanding of the universalization formulations; the second on a misunderstanding of the concept of an obligation; the third on a misunderstanding of the concept of a maxim; the fourth on a misunderstanding of the limits of action description; and the fifth on a misunderstanding of the universalization formulations again.
A Machine Learning Framework Predicts the Clinical Severity of Hemophilia B Caused by Point-Mutations
Authors: Lopes Tiago J. S. , Nogueira Tatiane , Rios Ricardo
Published: June 2022

Blood coagulation is a vital physiological mechanism to stop blood loss following an injury to a blood vessel. This process starts immediately upon damage to the endothelium lining a blood vessel, and results in the formation of a platelet plug that closes the site of injury. In this repair operation, an essential component is the coagulation factor IX (FIX), a serine protease encoded by the F9 gene and whose deficiency causes hemophilia B. If not treated by prophylaxis or gene therapy, patients with this condition are at risk of life-threatening bleeding episodes. In this sense, a deep understanding of the FIX protein and its activated form (FIXa) is essential to develop efficient therapeutics. In this study, we used well-studied structural analysis techniques to create a residue interaction network of the FIXa protein. Here, the nodes are the amino acids of FIXa, and two nodes are connected by an edge if the two residues are in close proximity in the FIXa 3D structure. This representation accurately captured fundamental properties of each amino acid of the FIXa structure, as we found by validating our findings against hundreds of clinical reports about the severity of HB. Finally, we established a machine learning framework named HemB-Class to predict the effect of mutations of all FIXa residues to all other amino acids and used it to disambiguate several conflicting medical reports. Together, these methods provide a comprehensive map of the FIXa protein architecture and establish a robust platform for the rational design of FIX therapeutics.
Vaspin Mediates the Intraorgan Crosstalk Between Heart and Adipose Tissue in Lipoatrophic Mice
Authors: Zhang Donghui , Zhu Hong , Zhan Enbo , Wang Fan , Liu Yue , Xu Wei , Liu Xian , Liu Jingjin , Li Shufeng , Pan Yong , Wang Yongshun , Cao Wei
Published: June 2022

Lipoatrophy is characterized as selective loss of adipose tissues, leading to the severity of cardiovascular disorders. Therefore, there was close intraorgan crosstalk between adipose tissue and cardiovascular in lipoatrophy. A-ZIP/F-1 mouse, a well-established lipoatrophic model, and primary cardiomyocytes were used for investigating the pathophysiological changes and molecular mechanisms. A-ZIP/F-1 mice had severe fat loss and impaired ventricular function during growth, but closely associated with the reduction of circulating vaspin levels. Administration of recombinant vaspin protein improved cardiac structural disorders, left ventricular dysfunction, and inflammatory response in lipoatrophic mice. In detail, vaspin decreased cardiac lipid deposits, but enhanced mitochondrial biogenesis and activities. Interestingly, A-ZIP/F-1 mice transplanted with normal visceral adipose tissues exhibited improvement in cardiac structural remodeling and mitochondrial function. Mechanistically, vaspin increased cardiac AKT activity, which guaranteed the mitochondrial benefits of vaspin in lipoatrophic mice and primary mouse cardiomyocytes. The present study suggested that vaspin possessed biological benefits in attenuating lipoatrophy-induced cardiomyopathy onset, and targeting vaspin/AKT signaling was a potential strategy to maintain heart metabolism.
Stakeholder’s Perspectives of the Twenty-First Century Skills
Authors: Mahmud Malissa Maria , Wong Shiau Foong
Published: June 2022

Today, the shift toward technology industries has made the applicable skills in high demand in the workforce. However, job training and education in general have not changed enough to keep up with the on-going trends. Concerns over the skills gap in our global workforce have exploded. In response to the demands of labor market and to close the skills gap, educational institution should focus on supporting skill development to cultivate the competencies that students need, making education in twenty-first century skills essential to prepare the students for the new and unknown in this fast-changing world of technology. This research aims to investigate the importance of twenty-first century skills for the employability of undergraduate students. The findings indicate that twenty-first century skills are the needed employability attributes, which transcend beyond qualifications and experience, that employers are looking for. It is also discovered from this study that the most effective way to attain twenty-first century skill is to focus on integrating twenty-first century knowledge and skills into the education support systems for our nation to realize its goal of successfully meeting the challenge of the twenty-first century.
Chronic and Cumulative Adverse Life Events in Women with Primary Ovarian Insufficiency: An Exploratory Qualitative Study
Authors: Sun Junyan , Fan Yihui , Guo Ying , Pan Huiying , Zhang Chen , Mao Guoping , Huang Yating , Li Boning , Gu Tingting , Wang Lulu , Zhang Qiuwan , Wang Qian , Zhou Qian , Li Bai , Lai Dongmei
Published: June 2022

Background and Purpose

Primary ovarian insufficiency (POI) has serious physical and psychological consequences due to estradiol deprivation, leading to increased morbidity and mortality. However, the causes of most POI cases remain unknown. Psychological stress, usually caused by stressful life events, is known to be negatively associated with ovarian function. It is important to explore high-frequency adverse life events among women with POI for future interventions.

Methods

Forty-three women (mean age=33·8 years) were recruited who were newly- diagnosed with idiopathic POI (FSH levels >40 IU/L) to participate in semi-structured interviews through convenience sampling. The main questions covered by the topic guide were designed to explore adverse life events prior to POI diagnosis. Interviews were audio recorded, transcribed and analyzed thematically. Data were analyzed from June 2019 to August 2020.

Results

Among the women with POI, mean age at diagnosis of POI was 33·8 years (range from 19 to 39 years), and the average time between the onset of irregular menstruation and POI diagnosis was 2.3 years. These women with POI had a relatively normal menstrual cycle before the diagnosis. A number of stressful life events prior to POI diagnosis were discussed by them as important factors influencing their health. Four core themes emerged: 1) persistent exposure to workplace stress, 2) persistent exposure to family-related adverse life events, 3) sleep problem/disturbance existed in women with POI before diagnosis, and 4) participants’ general cognition and concerns about POI.

Conclusions

Persistent exposures to adverse life events related to work stress, family stress and sleep problem existed in women with POI. Our findings are consistent with the hypothesis that adverse life events play a role in the development of POI. Future research should investigate how social environmental factors influence POI disease risks, and whether provision of tailored interventions (i.e. preventing or mitigating impact of adverse life events) aimed at high-risk populations may help prevent new POI cases and improve conditions of women with POI. We gained an in-depth understanding of the experiences of these women via 1:1 qualitative method, and find adverse life events are frequent in women with POI prior to the diagnosis.
Safety Parameters of Quantum Molecular Resonance Devices During Thyroid Surgery: Porcine Model Using Continuous Neuromonitoring
Authors: Tseng Hsin-Yi , Huang Tzu-Yen , Lin Yi-Chu , Wang Jia Joanna , Ko How-Yun , Chuang Cheng-Hsun , Lu I-Cheng , Chang Pi-Ying , Randolph Gregory W. , Dionigi Gianlorenzo , Chang Ning-Chia , Wu Che-Wei
Published: June 2022

Objectives

Quantum molecular resonance (QMR) devices have been applied as energy-based devices in many head and neck surgeries; however, research on their use in thyroid surgery is lacking. This study aimed to investigate the safety parameters of QMR devices during thyroidectomy when dissection was adjacent to the recurrent laryngeal nerve (RLN).

Methods

This study included eight piglets with 16 RLNs, and real-time electromyography (EMG) signals were obtained from continuous intraoperative neuromonitoring (C-IONM). QMR bipolar scissor (BS) and monopolar unit (MU) were tested for safety parameters. In the activation study, QMR devices were activated at varying distances from the RLN. In the cooling study, QMR devices were cooled for varying time intervals, with or without muscle touch maneuver (MTM) before contacting with the RLN.

Results

In the activation study, no adverse EMG change occurred when QMR BS and MU were activated at distances of 2 mm or longer from the RLNs. In the cooling study, no adverse EMG change occurred when QMR BS and MU were cooled in 2-second intervals or immediately after MTM.

Conclusion

QMR devices should be carefully used when performing RLN dissection during thyroid surgery. According to the activation and cooling safety parameters in this study, surgeons can avoid RLN injury by following standard procedures when using QMR devices.
Changes in Vertebral Marrow Fat Fraction Using 3D Fat Analysis & Calculation Technique Imaging Sequence in Aromatase Inhibitor-Treated Breast Cancer Women
Authors: Wan Taihu , Zhu Yuhang , Han Qinghe , Liu Lin
Published: June 2022

Aromatase inhibitor (AI) is a cornerstone drug for postmenopausal women with estrogen receptor-positive early-stage breast cancer. Fat-bone interactions within the bone marrow milieu are growing areas of scientific interest. Although AI treatment could lead to deterioration of the skeleton, the association between AI medication and subsequent marrow adiposity remains elusive. A total of 40 postmenopausal, early-staged, and hormone receptor-positive breast cancer patients who underwent treatment with adjuvant AIs and 40 matched controls were included. Marrow proton density fat fraction (PDFF) at the L1−L4 vertebral bodies using 3D Fat Analysis & Calculation Technique imaging (FACT) sequence at 3.0T, bone mineral density (BMD) by dual-energy X-ray absorptiometry, and serum bone turnover biomarkers were determined at baseline and at 6 and 12 months. We found that, in comparison to baseline, an increase of type I collagen cross-linked telopeptide was detected at 12 months (P <0.05). From baseline to 12 months, the PDFF measured using FACT was greatly increased. At 12 months, the median percent change of PDFF (4.9% vs. 0.9%, P <0.05) was significantly different between the AI treatments and controls. The same trend was observed for the marrow PDFF at 6 months relative to the respective values at baseline. Although BMD values were significantly reduced after 12 months in AI-treated women, changes in BMD vs. baseline condition were not significantly different between the AI-treated and control groups [Δ BMD −1.6% to −1.8% vs. −0.3% to −0.6%, respectively, P > 0.05]. In the AI-treated group, Δ PDFF was associated with Δ BMD at the lumbar spine (r = −0.585, P < 0.001), but not in the controls. Taken together, over a 12-month period, spinal marrow fat content assessed with FACT sequence significantly increased in postmenopausal women with hormone-receptor-positive breast cancer receiving AI treatment.
Decoding the Immune Microenvironment of Clear Cell Renal Cell Carcinoma by Single-Cell Profiling to Aid Immunotherapy
Authors: Liu Jie , Xu Jiangfan , Zhang Tong , Xu Kailong , Bao Peihua , Zhang Zhibo , Xue Kaiwen , He Ruyi , Ma Lixin , Wang Yang
Published: June 2022

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, and it is the major cause of kidney cancer death. Understanding tumor immune microenvironments (TMEs) is critical in cancer immunotherapies. Here, we studied the immune characterization at single-cell resolution by integrating public data of ccRCC across different tissue types, and comparing the transcriptome features and tumor TME differences in tumors, normal adjacent tissue, and peripheral blood. A total of 16 different types of cell components of ccRCC were identified. We revealed that there is an overall increase in T-cell and myeloid populations in tumor-infiltrated immune cells compared to normal renal tissue, and the B-cell population in the tumor showed a sharp decrease, which indicates that the cells in tumor tissue undergo strong immune stress. In addition, the cell–cell communication analysis revealed specific or conserved signals in different tissue types, which may aid to uncover the distinct immune response. By combining and analyzing publicly available ccRCC bulk RNA-seq datasets, 10 genes were identified as marker genes in specific cell types, which were significantly associated with poor prognosis. Of note, UBE2C, which may be a good indicator of tumor proliferation, is positively associated with reductions in overall survival and highly associated with tumor grade. Our integrated analysis provides single-cell transcriptomic profiling of ccRCC and their TME, and it unmasked new correlations between gene expression, survival outcomes, and immune cell-type components, enabling us to dissect the dynamic variables in the tumor development process. This resource provides deeper insight into the transcriptome features and immune response of ccRCC and will be helpful in kidney cancer immunotherapy.
Activation of Cholinergic Anti-Inflammatory Pathway Ameliorates Cerebral and Cardiac Dysfunction After Intracerebral Hemorrhage Through Autophagy
Authors: Su Yue , Zhang Wei , Zhang Ruoxi , Yuan Quan , Wu Ruixia , Liu Xiaoxuan , Wuri Jimusi , Li Ran , Yan Tao
Published: June 2022

Background

Intracerebral hemorrhage (ICH) is the devastating subtype of stroke with cardiovascular complications, resulting in high rates of mortality and morbidity with the release of inflammatory factors. Previous studies have demonstrated that activation of α7nAChR can reduce immune and inflammation-related diseases by triggering the cholinergic anti-inflammatory pathway (CAIP). α7nAChR mediates protection from nervous system inflammation through AMPK-mTOR-p70S6K-associated autophagy. Therefore, the purpose of this study is to explore whether the activation of α7nAChR improves cerebral and cardiac dysfunction after ICH through autophagy.

Methods

Male C57BL/6 mice were randomly divided into five groups (1): Control + saline (2), ICH+ saline (3), ICH + PNU-282987 (4), ICH+ PNU-282987 + MLA (5), ICH + PNU-282987 + 3-MA. The neurological function was evaluated at multiple time points. Brain water content was measured at 3 days after ICH to assess the severity of brain edema. PCR, immunofluorescence staining, and Western Blot were performed at 7 days after ICH to detect inflammation and autophagy. Picro-Sirius Red staining was measured at 30 days after ICH to evaluate myocardial fibrosis, echocardiography was performed at 3 and 30 days to measure cardiac function.

Results

Our results indicated that the PNU-282987 reduced inflammatory factors (MCP-1, IL-1β, MMP-9, TNF-α, HMGB1, TLR2), promoted the polarization of macrophage/microglia into anti-inflammatory subtypes(CD206), repaired blood-brain barrier injury (ZO-1, Claudin-5, Occludin), alleviated acute brain edema and then recovered neurological dysfunction. Echocardiography and PSR indicated that activation of α7nAChR ameliorated cardiac dysfunction. Western Blot showed that activation of α7nAChR increased autophagy protein (LC3, Beclin) and decreased P62. It demonstrated that the activation of α7nAChR promotes autophagy and then recovers brain and heart function after ICH.

Conclusions

In conclusion, PNU-282987 promoted the cerebral and cardiac functional outcomes after ICH in mice through activated α7nAChR, which may be attributable to promoting autophagy and then reducing inflammatory reactions after ICH.
Development and Verify of Survival Analysis Models for Chinese Patients With Systemic Lupus Erythematosus
Authors: Geng Linyu , Qu Wenqiang , Liang Jun , Kong Wei , Xu Xue , Pan Wenyou , Liu Lin , Wu Min , Ding Fuwan , Hu Huaixia , Ding Xiang , Wei Hua , Zou Yaohong , Qian Xian , Wang Meimei , Wu Jian , Tao Juan , Tan Jun , Da Zhanyun , Zhang Miaojia , Li Jing , Zhang Huayong , Feng Xuebing , Chen Jiaqi , Sun Lingyun
Published: June 2022

Background

The aim of this study is to develop survival analysis models of hospitalized systemic lupus erythematosus (h-SLE) patients in Jiangsu province using data mining techniques to predict patient survival outcomes and survival status.

Methods

In this study, based on 1999–2009 survival data of 2453 hospitalized SLE (h-SLE) patients in Jiangsu Province, we not only used the Cox proportional hazards model to analyze patients’ survival factors, but also used neural network models to predict survival outcomes. We used semi-supervised learning to label the censored data and introduced cost-sensitivity to achieve data augmentation, addressing category imbalance and pseudo label credibility. In addition, the risk score model was developed by logistic regression.

Results

The overall accuracy of the survival outcome prediction model exceeded 0.7, and the sensitivity was close to 0.8, and through the comparative analysis of multiple indicators, our model outperformed traditional classifiers. The developed survival risk assessment model based on logistic regression found that there was a clear threshold, i.e., a survival threshold indicating the survival risk of patients, and cardiopulmonary and neuropsychiatric involvement, abnormal blood urea nitrogen levels and alanine aminotransferase level had the greatest impact on patient survival time. In addition, the study developed a graphical user interface (GUI) integrating survival analysis models to assist physicians in diagnosis and treatment.

Conclusions

The proposed survival analysis scheme identifies disease-related pathogenic and prognosis factors, and has the potential to improve the effectiveness of clinical interventions.
Helper-Like Type-1 Innate Lymphoid Cells in Inflammatory Bowel Disease
Authors: Coman Diana , Coales Isabelle , Roberts Luke B. , Neves Joana F.
Published: June 2022

Inflammatory bowel disease (IBD) is an idiopathic condition characterized by chronic relapsing inflammation in the intestine. While the precise etiology of IBD remains unknown, genetics, the gut microbiome, environmental factors, and the immune system have all been shown to contribute to the disease pathophysiology. In recent years, attention has shifted towards the role that innate lymphoid cells (ILCs) may play in the dysregulation of intestinal immunity observed in IBD. ILCs are a group of heterogenous immune cells which can be found at mucosal barriers. They act as critical mediators of the regulation of intestinal homeostasis and the orchestration of its inflammatory response. Despite helper-like type 1 ILCs (ILC1s) constituting a particularly rare ILC population in the intestine, recent work has suggested that an accumulation of intestinal ILC1s in individuals with IBD may act to exacerbate its pathology. In this review, we summarize existing knowledge on helper-like ILC1 plasticity and their classification in murine and human settings. Moreover, we discuss what is currently understood about the roles that ILC1s may play in the progression of IBD pathogenesis.
DDOST Correlated with Malignancies and Immune Microenvironment in Gliomas
Authors: Chang Xiaojing , Pan Jie , Zhao Ruoyu , Yan Tianfang , Wang Xinrui , Guo Cunle , Yang Yining , Wang Guohui
Published: June 2022

Among the most common types of brain tumor, gliomas are the most aggressive and have the poorest prognosis. Dolichyl-diphosphooligosaccharide protein glycosyltransferase non-catalytic subunit (DDOST) encodes a component of the oligosaccharide transferase complex and is related to the N-glycosylation of proteins. The role of DDOST in gliomas, however, is not yet known. First, we performed a pan cancer analysis of DDOST in the TCGA cohort. The expression of DDOST was compared between glioma and normal brain tissues in the GEO and Chinese Glioma Genome Atlas (CGGA) databases. In order to explore the role of DDOST in glioma, we analyze the impact of DDOST on the prognosis of glioma patients, with the CGGA 325 dataset as a test set and the CGGA 693 dataset as a validation set. Immunohistochemistry was performed on tissue microarrays to examine whether DDOST has an impact on glioma patient survival. Next, using single-cell sequencing analysis, GSEA, immune infiltration analysis, and mutation analysis, we explored how DDOST affected the glioma tumor microenvironment. Finally, we evaluated the clinical significance of DDOST for glioma treatment by constructing nomograms and decision curve analysis (DCA) curves. We found that DDOST was overexpressed in patients with high grade, IDH wild type, 1p19q non-codel and MGMT un-methylated, which was associated with poor prognosis. Patients with high levels of DDOST, regardless of their clinical characteristics, had a worse prognosis. Immunohistochemical analysis confirmed the results of the above bioinformatics analysis. Mechanistic analysis revealed that DDOST was closely associated with the glioma microenvironment and negatively related to tumor-infiltrating B cells and CD4+ T cells and positively related to CAFs and tumor-associated macrophages. In conclusion, these findings suggested that DDOST mediated the immunosuppressive microenvironment of gliomas and could be an important biomarker in diagnosing and treating gliomas.
Enhanced Therapeutic Efficacy of Combining Losartan and Chemo-Immunotherapy for Triple Negative Breast Cancer
Authors: Zhao Qing , He Xuexin , Qin Xiyi , Liu Yu , Jiang Han , Wang Jing , Wu Shuang , Zhou Rui , Yu Congcong , Liu Suling , Zhang Hong , Tian Mei
Published: June 2022

Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, which is relatively resistant to anti-programmed cell death-1 (α-PD1) therapy, characterized as non-immunogenic, dense stroma and accumulation of M2 tumor-associated macrophages (TAMs). Despite progress in strategies to deplete extracellular matrix (ECM) and enhance tumor-cell immunogenicity, the combinatorial anti-cancer effects with α-PD1 need to be explored. Here, we applied doxorubicin hydrochloride liposome (Dox-L) as immunogenic cell death (ICD)-inducing nano-chemotherapy and used losartan as stroma-depleting agent to improve α-PD1 efficacy (Losartan + Dox-L + α-PD1). The results showed that losartan could cause ECM reduction, facilitating enhanced delivery of Dox-L and further dendritic cell (DC) maturation. Additionally, losartan could also alleviate hypoxia for TNBC, thus reprogramming pro-cancer M2 TAMs to anti-cancer M1 TAMs, successfully overcoming immune-suppressive microenvironment. These modifications led to a significant increase in T cells’ infiltration and augmented anti-tumor immunity as exemplified by the notable reduction in tumor size and lung metastases. In summary, our findings support that combined treatment of losartan with Dox-L normalizes immunological-cold microenvironment, improves immuno-stimulation and optimizes the efficacy of TNBC immunotherapy. A novel combinational strategy with FDA-approved compounds proposed by the study may potentially be useful in TNBC clinical treatment.
Photonic Type-III Nodal Loop and Topological Phase Transitions at Bilayer Metasurfaces
Authors: Li Haitao , Hu Chuandeng , Jiang Jian-Hua , Wu Jinbo , Wen Weijia , Hou Bo
Published: June 2022

In momentum space, the nodal loop is regarded as a ring-shaped band degeneracy and is classified into type-I and type-II configurations depending on the positive/negative dispersions of the degenerating bands. Here, we experimentally observe a new class of nodal loop in the photonic band structure, employing an artificially designed bilayer metasurface. Such degeneracy, termed type-III nodal loop, is formed by the crossing between a resonant flat band and a positively dispersive band and is protected by mirror symmetry Mz, which manifests in the metasurface’s bilayer architecture. Furthermore, the sequential topological transitions of band degeneracy from the nodal loop via Dirac point to gapped phase are demonstrated at the metasurfaces. Such transitions are enabled by the bilayer design and end with a pair of edge states on the domain wall of gapped systems. Our work reveals that properly engineered bilayer metasurfaces offer rich physics and vast flexibility in two-dimensional topological photonic research through assembling and tunning more symmetries and degrees of freedom along the stacking direction.
Serum Total Bilirubin With Hospital Survival in Adults During Extracorporeal Membrane Oxygenation
Authors: Huang Rui , Shao Min , Zhang Cheng , Fang Ming , Jin Mengmeng , Han Xuan , Liu Nian
Published: June 2022

Background

Extracorporeal membrane oxygenation (ECMO) is widely used for refractory cardiopulmonary failure treatment. The disadvantage of ECMO is its higher risk profile and clinical resource consumption. This observation examines the role of serum total bilirubin (TBIL) as a predictor of adult patient outcomes on ECMO support.

Methods

This retrospective observation reports a single-center experience with adults on ECMO support between 2018 and 2021. Data were collected regarding demographics, ECMO details, laboratory parameters, and outcomes. We examined the elevation of TBIL to predict survival and variables associated with hyperbilirubinemia.

Results

The patients who died within 28 days had a twofold higher peak level of TBIL than those who survived [73.10 (38.60, 98.64) vs. 34.50 (24.03, 54.85); P = 0.003]. Univariate logistic regression analyses demonstrated that high TBIL was remarkably associated with an elevated risk of 28-day mortality (OR: 7.25; 95% CI: 2.31–25.49; P = 0.001) and total mortality (OR: 5.71; 95% CI: 1.82–20.66; P = 0.001). The TBIL value was 65 μmol/L as the best cut-off value, and the observation group was divided into a high TBIL subgroup (n = 21) or a low TBIL subgroup (n = 39). The demographic and clinical features did not show a difference, whereas Sequential Organ Failure Assessment (SOFA) and APACHE II scores and ALT, AST, and LAC before ECMO initiation correlated with high or low TBIL (P < 0.05). For coagulation function at the time of TBIL peak, the levels of prothrombin time (PT), activated partial thromboplastin time (APTT), prothrombin time activity (PTA), and fibrinogen (FIB) were different between the two subgroups (P < 0.05). The SOFA score was potentially associated with hyperbilirubinemia after ECMO initiation, and the prediction accuracy was 0.800.

Conclusion

Serum total bilirubin elevation appears after ECMO initiation and correlates with survival, while other markers of liver injury do not. Serum total bilirubin is an easy-to-measure biomarker to be a predictor of survival after ECMO initiation.
Evaluating the Non-conventional Achalasia Treatment Modalities
Authors: Tustumi Francisco
Published: June 2022

Introduction

Achalasia is a primary esophageal dysmotility disorder. Despite the high volume of studies addressing the conventional treatments for achalasia, few are debated regarding the non-conventional treatments, such as cardiectomy, cardioplasty, endoluminal substances injection (ethanolamine oleate, polidocanol, botulinum toxin), stents, and certain drugs (beta-agonists, anticholinergic, nitrates, calcium channel blockers, and phosphodiesterase inhibitors).

Methods

A critical review was performed.

Results

Endoscopic, surgical, and pharmacological treatments were included. A qualitative synthesis was presented.

Conclusion

Non-conventional therapeutic options for treating achalasia encompass medical, endoscopic, and surgical procedures. Clinicians and patients need to know all the tools for the management of achalasia. However, several currently available studies of non-conventional treatments lack high-quality evidence, and future randomized trials are still needed.
Association Between Fat Graft Retention and Blood Flow in Localized Scleroderma Patients: A Pilot Study
Authors: Wang Hayson Chenyu , Li Yunzhu , Li Zhujun , Wang Liquan , Li Ziming , Long Xiao
Published: June 2022

Background

Microcirculation plays a vital role in scleroderma physiopathology and the mechanism of fat survival.

Objective

This study aims to assess the blood perfusion change after fat grafting and evaluate the relationship between blood perfusion and fat graft retention in patients with localized scleroderma (LS).

Methods

A pilot study was conducted in patients with LS receiving autologous fat grafting (AFG). Fat graft retention measured by magnetic resonance imaging (MRI) analysis and blood flow perfusion measured by laser speckle contrast imaging 6 months postoperatively were noted. PUMC Localized Scleroderma Facial Aesthetic Index was used to assess the improvement of facial aesthetic impairment.

Results

The fat retention at the 6-month follow-up was 34.56 ± 11.89 percent. At the 6th month of follow-up, the relative blood perfusion at the lesion area was 115.08 ± 14.39 PU, significantly higher than 100.42 ± 10.62 PU at the pre-operation (p = 0.010). The blood perfusion at follow-up increased by an average of 1.15 ± 0.14 times before the operation. No association between the increase in the blood flow perfusions and fat graft retention was found (r = −0.082, p = 0.811).

Conclusion

Local blood perfusion in the lesion area relatively increased after AFG, but no direct relationship was found between fat retention and increased blood supply.
Wild and Captive Environments Drive the Convergence of Gut Microbiota and Impact Health in Threatened Equids
Authors: Zhou Zhichao , Tang Liping , Yan Liping , Jia Huiping , Xiong Yu , Shang Jin , Shao Changliang , Zhang Qiangwei , Wang Hongjun , He Lun , Hu Defu , Zhang Dong
Published: June 2022

To explore how the living environment influences the establishment of gut microbiota in different species, as well as the extent to which changes in the living environment caused by captive breeding affect wildlife’s gut microbiota and health, we used 16S rRNA gene amplicon sequencing and shotgun metagenomic sequencing to compare the gut microbiome of two species of threatened equids, the Przewalski’s Horse and the Asian wild ass, in the wild and captivity. The results revealed that different species of Equidae living in the same environment showed remarkable convergence of gut microflora. At the same time, captive populations exhibited significantly “unhealthy” microbiota, such as low Alpha diversity, high levels of potentially pathogenic bacteria and biomarkers of physical or psychological disease, and enrichment of microbial functions associated with exogenous exposure and susceptibility, implying that the artificial environment created by captivity may adversely impact the health of wildlife to some extent. Our findings demonstrate the importance of the environmental factors for the establishment of gut microbiota and host health and provide new insights into the conservation of wildlife in captivity from the perspective of the microbiome.
Antiviral Activity of Zinc Oxide Nanoparticles and Tetrapods Against the Hepatitis E and Hepatitis C Viruses
Authors: Gupta Jyoti , Irfan Minnah , Ramgir Niranjan , Muthe K. P. , Debnath A. K. , Ansari Shabnam , Gandhi Jaya , Ranjith-Kumar C. T. , Surjit Milan
Published: June 2022

Hepatitis E virus (HEV) causes an acute, self-limiting hepatitis. The disease takes a severe form in pregnant women, leading to around 30% mortality. Zinc is an essential micronutrient that plays a crucial role in multiple cellular processes. Our earlier findings demonstrated the antiviral activity of zinc salts against HEV infection. Zinc oxide (ZnO) and its nanostructures have attracted marked interest due to their unique characteristics. Here we synthesized ZnO nanoparticles [ZnO(NP)] and tetrapod-shaped ZnO nanoparticles [ZnO(TP)] and evaluated their antiviral activity. Both ZnO(NP) and ZnO(TP) displayed potent antiviral activity against hepatitis E and hepatitis C viruses, with the latter being more effective. Measurement of cell viability and intracellular reactive oxygen species levels revealed that both ZnO(NP) and ZnO(TP) are noncytotoxic to the cells even at significantly higher doses, compared to a conventional zinc salt (ZnSO4). Our study paves the way for evaluation of the potential therapeutic benefit of ZnO(TP) against HEV and HCV.
Microbial Succession and Interactions During the Manufacture of Fu Brick Tea
Authors: Xiang Meichun , Chu Jun , Cai Wenjiao , Ma Haikun , Zhu Weijing , Zhang Xiaoling , Ren Jinwei , Xiao Lizheng , Liu Dongbo , Liu Xingzhong
Published: June 2022

Fu Brick tea is a very popular post-fermented tea that is known for its “golden flower fungus,” Aspergillus cristatus, which becomes the dominant microbe during the maturation process. This study used both culture-dependent methods and high-throughput sequencing to track microbial succession and interactions during the development of the golden flower fungus, a crucial component of the manufacturing process of Fu Brick tea. Among the bacterial communities, Klebsiella and Lactobacillus were consistently cultured from both fresh tea leaves and in post-fermentation Fu Brick tea. Methylobacterium, Pelomonas, and Sphingomonas were dominant genera in fresh tea leaves but declined once fermentation started, while Bacillus, Kluyvera, and Paenibacillus became dominant after piling fermentation. The abundance of A. cristatus increased during the manufacturing process, accounting for over 98% of all fungi present after the golden flower bloom in the Fu Brick tea product. Despite their consistent presence during culture work, network analysis showed Lactobacillus and Klebsiella to be negatively correlated with A. cristatus. Bacillus spp., as expected from culture work, positively correlated with the presence of golden flower fungus. This study provides complete insights about the succession of microbial communities and highlights the importance of co-occurrence microbes with A. cristatus during the manufacturing process of Fu Brick tea.
Transcriptomic and Phenomic Investigations Reveal Elements in Biofilm Repression and Formation in the Cyanobacterium Synechococcus elongatus PCC 7942
Authors: Simkovsky Ryan , Parnasa Rami , Wang Jingtong , Nagar Elad , Zecharia Eli , Suban Shiran , Yegorov Yevgeni , Veltman Boris , Sendersky Eleonora , Schwarz Rakefet , Golden Susan S.
Published: June 2022

Biofilm formation by photosynthetic organisms is a complex behavior that serves multiple functions in the environment. Biofilm formation in the unicellular cyanobacterium Synechococcus elongatus PCC 7942 is regulated in part by a set of small secreted proteins that promotes biofilm formation and a self-suppression mechanism that prevents their expression. Little is known about the regulatory and structural components of the biofilms in PCC 7942, or response to the suppressor signal(s). We performed transcriptomics (RNA-Seq) and phenomics (RB-TnSeq) screens that identified four genes involved in biofilm formation and regulation, more than 25 additional candidates that may impact biofilm formation, and revealed the transcriptomic adaptation to the biofilm state. In so doing, we compared the effectiveness of these two approaches for gene discovery.
Global Prevalence of Domestic Cat Hepadnavirus: An Emerging Threat to Cats’ Health?
Authors: Shofa Maya , Kaneko Yasuyuki , Takahashi Kazuki , Okabayashi Tamaki , Saito Akatsuki
Published: June 2022

Hepatitis B is an infectious hepatocellular disease of global concern caused by hepatitis B virus (HBV), which belongs to Hepadnaviridae. Recently, a novel HBV-like virus, domestic cat hepadnavirus (DCH), was detected from an immunocompromised cat with a hepatic disease in Australia. Subsequent molecular investigation by independent research groups revealed that its prevalence rates were 6.5% in Australia, 10.8% in Italy, 12.4% in Thailand, 12.3% in Malaysia, 3.08% in the United Kingdom, and 0.78% in Japan. Although the correlation between DCH infection and hepatic diseases remains to be elucidated, understanding the diversity of circulating DCH will contribute to its prevention and control in domestic cats. Herein, we summarize the current epidemiological data of DCH in these countries.
Identification of Pyroptosis-Related Gene Signatures and Construction of the Risk Model to Predict BCR in Prostate Cancer
Authors: Wang Miaomiao , Xia Haoran , Yan Qiuxia , Liu Wen , Liu Ming , Wang Xuan
Published: June 2022

Prostate cancer is one of the most common malignant tumors in men. Pyroptosis is related to tumor immune infiltration and tumor microenvironment (TME) and has been confirmed to be related to the progression of a variety of tumors. However, the relationship between prostate cancer and pyroptosis, as well as TME and tumor immune infiltration, has not been discussed yet. We obtained and combined the RNA-seq data of prostate cancer from TCGA and GEO databases, analyzed the differential expression of pyroptosis-related genes (PRGs), and divided them into two groups according to the PRG expression level. The relationship between pyroptosis subtypes and the TME of prostate cancer was further verified, and the differential expression genes (DEGs) in the two subtypes were identified. The relationship between the DEGs and clinicopathology was explored and KEGG and GO enrichment analysis was conducted; it was found that most DEGs were enriched in immune-related pathways. Then, we randomly divided datasets into training and testing sets, performed the LASSO and multicox progression analysis, selected eight genes as prognostic signatures and used the eight genes, calculated the risk score, and then separated the entire cohort into high- and low-risk groups. The prognosis between two groups and the 1-, 3-, and 5-year ROC curves of biochemical relapse (BCR) were verified in training, testing, and the entire cohort, respectively. The TME, CSC index, mutation, and drug susceptibility were also discussed.
Cannabinoid Effect and Safety in Spasticity Following Stroke: A Double-Blind Randomized Placebo-Controlled Study
Authors: Marinelli Lucio , Puce Luca , Mori Laura , Leandri Massimo , Rosa Gian Marco , Currà Antonio , Fattapposta Francesco , Trompetto Carlo
Published: June 2022

Background

Nabiximols is a cannabis-based drug to treat spasticity-associated symptoms currently approved for patients with multiple sclerosis only. Cannabinoids are useful in an increasing number of medical conditions but may bear an increased risk for cardiovascular events. SativexStroke is a double-blind randomized placebo-controlled crossover monocentric clinical trial investigating the efficacy and safety of nabiximols in patients with spasticity following stroke.

Methods

Patients were treated with nabiximols oromucosal spray or placebo and assessed before and after two phases of 1-month duration each. Cardiovascular safety was assessed before and during the trial. Primary endpoints were changes in spasticity numeric rating scale scores and electromyographic recording of the stretch reflex in affected wrist flexors. Secondary outcome measures were numeric rating scale scores for pain, sleep and bladder function, the number of daily spasms and clinical assessment of spasticity with the modified Ashworth scale. The study was registered with the EudraCT number 2016-001034-10.

Results

Between May 2, 2018, and February 20, 2020, 41 patients entered the study. Seven patients did not complete the study, so 34 were included in the analysis. Two serious adverse events occurred, but none related to cardiovascular function. Primary and secondary efficacy outcome measures did not change from baseline during nabiximols treatment relative to placebo.

Conclusion

This study suggests that nabiximols use is probably safe in stroke patients, therefore cannabinoid usefulness may be further investigated. The lack of nabiximols effect could be related to low pain levels in recruited patients or different spasticity mechanisms between post-stroke and multiple sclerosis patients. Similarly, a beneficial effect of nabiximols could have emerged if more patients with a higher level of spasticity at baseline were recruited.

Clinical Trial Registration

https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001034-10/IT.
Foot Assessment Clinical Scales in Charcot-Marie-Tooth Patients: A Scoping Review
Authors: Rambelli Chiara , Mazzoli Davide , Galletti Martina , Basini Giacomo , Zerbinati Paolo , Prati Paolo , Mascioli Francesca , Masiero Stefano , Merlo Andrea
Published: June 2022

Introduction

Charcot-Marie-Tooth disease (CMT) is a slow and progressive peripheral motor sensory neuropathy frequently associated with the cavo-varus foot deformity. We conducted a scoping review on the clinical scales used to assess foot deviations in CMT patients and analyzed their metric properties.

Evidence Acquisition

A first search was conducted to retrieve all scales used to assess foot characteristics in CMT patients from the Medline, Web of Science, Google Scholar, Cochrane, and PEDro databases. A second search was conducted to include all studies that evaluated the metric properties of such identified scales from the same databases. We followed the methodologic guidelines specific for scoping reviews and used the PICO framework to set the eligibility criteria. Two independent investigators screened all papers.

Evidence Synthesis

The first search found 724 papers. Of these, 41 were included, using six different scales: “Foot Posture Index” (FPI), “Foot Function Index”, “Maryland Foot Score”, “American Orthopedic Foot & Ankle Society's Hindfoot Evaluation Scale”, “Foot Health Status Questionnaire”, Wicart-Seringe grade. The second search produced 259 papers. Of these, 49 regarding the metric properties of these scales were included. We presented and analyzed the properties of all identified scales in terms of developmental history, clinical characteristics (domains, items, scores), metric characteristics (uni-dimensionality, inter- and intra-rater reliability, concurrent validity, responsiveness), and operational characteristics (normative values, manual availability, learning time and assessors' characteristics).

Conclusions

Our results suggested the adoption of the six-item version of the FPI scale (FPI-6) for foot assessment in the CMT population, with scoring provided by Rasch Analysis. This scale has demonstrated high applicability in different cohorts after a short training period for clinicians, along with good psychometric properties. FPI-6 can help health professionals to assess foot deformity in CMT patients over the years.
Multidimensional Assessment of Electroencephalography in the Neuromodulation of Disorders of Consciousness
Authors: Zhang Chunyun , Han Shuai , Li Zean , Wang XinJun , Lv Chuanxiang , Zou Xiangyun , Zhu Fulei , Zhang Kang , Lu Shouyong , Bie Li , Lv Guoyue , Guo Yongkun
Published: June 2022

In the present study, we aimed to elucidate changes in electroencephalography (EEG) metrics during recovery of consciousness and to identify possible clinical markers thereof. More specifically, in order to assess changes in multidimensional EEG metrics during neuromodulation, we performed repeated stimulation using a high-density transcranial direct current stimulation (HD-tDCS) protocol in 42 patients with disorders of consciousness (DOC). Coma Recovery Scale-Revised (CRS-R) scores and EEG metrics [brain network indicators, spectral energy, and normalized spatial complexity (NSC)] were obtained before as well as fourteen days after undergoing HD-tDCS stimulation. CRS-R scores increased in the responders (R +) group after HD-tDCS stimulation. The R + group also showed increased spectral energy in the alpha2 and beta1 bands, mainly at the frontal and parietal electrodes. Increased graphical metrics in the alpha1, alpha2, and beta1 bands combined with increased NSC in the beta2 band in the R + group suggested that improved consciousness was associated with a tendency toward stronger integration in the alpha1 band and greater isolation in the beta2 band. Following this, using NSC as a feature to predict responsiveness through machine learning, which yielded a prediction accuracy of 0.929, demonstrated that the NSC of the alpha and gamma bands at baseline successfully predicted improvement in consciousness. According to our findings reported herein, we conclude that neuromodulation of the posterior lobe can lead to an EEG response related to consciousness in DOC, and that the posterior cortex may be one of the key brain areas involved in the formation or maintenance of consciousness.
Metabolomics: The Key to Unraveling the Role of the Microbiome in Visceral Pain Neurotransmission
Authors: Shute Adam , Bihan Dominique G. , Lewis Ian A. , Nasser Yasmin
Published: June 2022

Inflammatory bowel disease (IBD), comprising Crohn’s disease and Ulcerative colitis, is a relapsing and remitting disease of the gastrointestinal tract, presenting with chronic inflammation, ulceration, gastrointestinal bleeding, and abdominal pain. Up to 80% of patients suffering from IBD experience acute pain, which dissipates when the underlying inflammation and tissue damage resolves. However, despite achieving endoscopic remission with no signs of ongoing intestinal inflammation or damage, 30–50% of IBD patients in remission experience chronic abdominal pain, suggesting altered sensory neuronal processing in this disorder. Furthermore, effective treatment for chronic pain is limited such that 5–25% of IBD outpatients are treated with narcotics, with associated morbidity and mortality. IBD patients commonly present with substantial alterations to the microbial community structure within the gastrointestinal tract, known as dysbiosis. The same is also true in irritable bowel syndrome (IBS), a chronic disorder characterized by altered bowel habits and abdominal pain, in the absence of inflammation. An emerging body of literature suggests that the gut microbiome plays an important role in visceral hypersensitivity. Specific microbial metabolites have an intimate relationship with host receptors that are highly expressed on host cell and neurons, suggesting that microbial metabolites play a key role in visceral hypersensitivity. In this review, we will discuss the techniques used to analysis the metabolome, current potential metabolite targets for visceral hypersensitivity, and discuss the current literature that evaluates the role of the post-inflammatory microbiota and metabolites in visceral hypersensitivity.