bluuebunny/crossref_metadata_2025 huggingface dataset:
Acceptability and usability of a patient portal for men with prostate cancer in follow-up care
Authors: O’Connor David , Frankland Jane , Watts Jo , Brodie Hazel , Hamer Kevin , Foster Claire , Richardson Alison
Published: November 2022

Background

A stratified approach to cancer follow-up care, including remote monitoring and supported self-management for suitable patients, is increasingly recommended. Patient portals can facilitate such an approach, allowing access to results and information. There is limited understanding of the use of portals within this context.

Aim

This paper reports the acceptability and usability of a patient portal developed to facilitate a remote monitoring and supported self-management follow-up care programme for men with prostate cancer.

Methods

A mixed methods evaluation, including analysis of service utilisation data, a survey of users' experiences and satisfaction, and telephone interviews of non-users' views and experiences.

Results

Sixty percent of eligible patients registered to use the portal. Of these, 37% logged in at least once over a 6-month period and 52% over 12 months. Satisfaction among these users was reasonably high. Use of the portal in general was rated as very easy or easy by over 70% of respondents, and the majority felt the portal had helped them manage their condition in various ways. However, a large minority (40%) did not use the portal, with reasons for non-use including lack of access to computing facilities and lack of computer skills. Those who were older were less likely to register to use the portal.

Conclusions

A large proportion of participants found the patient portal acceptable and easy to use. Reasons for non-use should be addressed in order to maximise system efficiencies and minimise inequalities in care, and the needs of specific groups should be taken into account.
Correlation between estimated glucose disposal rate and in-stent restenosis following percutaneous coronary intervention in individuals with non-ST-segment elevation acute coronary syndrome
Authors: Liu Chi , Zhao Qi , Zhao Ziwei , Ma Xiaoteng , Xia Yihua , Sun Yan , Zhang Dai , Liu Xiaoli , Zhou Yujie
Published: November 2022

Background

Insulin resistance (IR) is closely associated with in-stent restenosis (ISR) following percutaneous coronary intervention (PCI). Nevertheless, the predictive power of the newly developed simple assessment method for IR, estimated glucose disposal rate (eGDR), for ISR after PCI in individuals with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) remains unclear.

Methods

NSTE-ACS cases administered PCI in Beijing Anzhen Hospital between January and December 2015 were enrolled. The included individuals were submitted to at least one coronary angiography within 48 months after discharge. Patients were assigned to 2 groups according to ISR occurrence or absence. eGDR was derived as 21.16 - (0.09 * waist circumference [cm]) - (3.41 * hypertension) - (0.55 * glycated hemoglobin [%]). Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed for evaluating eGDR’s association with ISR.

Results

Based on eligibility criteria, 1218 patients were included. In multivariate logistic analysis, the odds ratios (ORs) of eGDR as a nominal variate and a continuous variate were 3.393 (confidence interval [CI] 2.099 - 5.488, P < 0.001) and 1.210 (CI 1.063 - 1.378, P = 0.004), respectively. The incremental effect of eGDR on ISR prediction based on traditional cardiovascular risk factors was reflected by ROC curve analysis (AUC: baseline model + eGDR 0.644 vs. baseline model 0.609, P for comparison=0.013), continuous net reclassification improvement (continuous-NRI) of -0.264 (p < 0.001) and integrated discrimination improvement (IDI) of 0.071 (p = 0.065).

Conclusion

In NSTE-ACS cases administered PCI, eGDR levels show an independent negative association with increased ISR risk.
Growth hormone in fertility and infertility: Mechanisms of action and clinical applications
Authors: Chang Chia-Wei , Sung Yu-Wen , Hsueh Ya-Wen , Chen Yi-Yan , Ho Ming , Hsu Hsi-Chen , Yang Tung-Chuan , Lin Wu-Chou , Chang Hsun-Ming
Published: November 2022

Secreted by the anterior pituitary gland, growth hormone (GH) is a peptide that plays a critical role in regulating cell growth, development, and metabolism in multiple targeted tissues. Studies have shown that GH and its functional receptor are also expressed in the female reproductive system, including the ovaries and uterus. The experimental data suggest putative roles for GH and insulin-like growth factor 1 (IGF-1, induced by GH activity) signaling in the direct control of multiple reproductive functions, including activation of primordial follicles, folliculogenesis, ovarian steroidogenesis, oocyte maturation, and embryo implantation. In addition, GH enhances granulosa cell responsiveness to gonadotropin by upregulating the expression of gonadotropin receptors (follicle-stimulating hormone receptor and luteinizing hormone receptor), indicating crosstalk between this ovarian regulator and the endocrine signaling system. Notably, natural gene mutation of GH and the age-related decline in GH levels may have a detrimental effect on female reproductive function, leading to several reproductive pathologies, such as diminished ovarian reserve, poor ovarian response during assisted reproductive technology (ART), and implantation failure. Association studies using clinical samples showed that mature GH peptide is present in human follicular fluid, and the concentration of GH in this fluid is positively correlated with oocyte quality and the subsequent embryo morphology and cleavage rate. Furthermore, the results obtained from animal experiments and human samples indicate that supplementation with GH in the in vitro culture system increases steroid hormone production, prevents cell apoptosis, and enhances oocyte maturation and embryo quality. The uterine endometrium is another GH target site, as GH promotes endometrial receptivity and pregnancy by facilitating the implantation process, and the targeted depletion of GH receptors in mice results in fewer uterine implantation sites. Although still controversial, the administration of GH during ovarian stimulation alleviates age-related decreases in ART efficiency, including the number of oocytes retrieved, fertilization rate, embryo quality, implantation rate, pregnancy rate, and live birth rate, especially in patients with poor ovarian response and recurrent implantation failure.
The regulatory activities of MALAT1 in the development of bone and cartilage diseases
Authors: Zhang Di , Xue Jinhua , Peng Fang
Published: November 2022

Long non-coding RNAs (lncRNAs) have been comprehensively implicated in various cellular functions by mediating transcriptional or post-transcriptional activities. MALAT1 is involved in the differentiation, proliferation, and apoptosis of multiple cell lines, including BMSCs, osteoblasts, osteoclasts, and chondrocytes. Interestingly, MALAT1 may interact with RNAs or proteins, regulating cellular processes. Recently, MALAT1 has been reported to be associated with the development of bone and cartilage diseases by orchestrating the signaling network. The involvement of MALAT1 in the pathological development of bone and cartilage diseases makes it available to be a potential biomarker for clinical diagnosis or prognosis. Although the potential mechanisms of MALAT1 in mediating the cellular processes of bone and cartilage diseases are still needed for further elucidation, MALAT1 shows great promise for drug development.
Application of metabolomics in osteoporosis research
Authors: Zhao Zhenyu , Cai Zhengwei , Chen Aopan , Cai Ming , Yang Kai
Published: November 2022

Osteoporosis (OP) is a systemic disease characterized by bone metabolism imbalance and bone microstructure destruction, which causes serious social and economic burden. At present, the diagnosis and treatment of OP mainly rely on imaging combined with drugs. However, the existing pathogenic mechanisms, diagnosis and treatment strategies for OP are not clear and effective enough, and the disease progression that cannot reflect OP further restricts its effective treatment. The application of metabolomics has facilitated the study of OP, further exploring the mechanism and behavior of bone cells, prevention, and treatment of the disease from various metabolic perspectives, finally realizing the possibility of a holistic approach. In this review, we focus on the application of metabolomics in OP research, especially the newer systematic application of metabolomics and treatment with herbal medicine and their extracts. In addition, the prospects of clinical transformation in related fields are also discussed. The aim of this study is to highlight the use of metabolomics in OP research, especially in exploring the pathogenesis of OP and the therapeutic mechanisms of natural herbal medicine, for the benefit of interdisciplinary researchers including clinicians, biologists, and materials engineers.
A review of mechanism and adsorption capacities of biochar-based engineered composites for removing aquatic pollutants from contaminated water
Authors: Murtaza Ghulam , Ahmed Zeeshan , Dai Dong-Qin , Iqbal Rashid , Bawazeer Sami , Usman Muhammad , Rizwan Muhammad , Iqbal Javed , Akram Muhammad Irfan , Althubiani Abdullah Safar , Tariq Akash , Ali Iftikhar
Published: November 2022

Water contamination by aquatic pollutants (antibiotics, heavy metals, nutrients, and organic pollutants) has become the most serious issue of recent times due to associated human health risks. Biochar (BC) has been deemed an effective and promising green material for the remediation of a wide range of environmental pollutants. Due to its limited properties (small pore size and low surface functionality), pristine BC has encountered bottlenecks in decontamination applications. These limitations can be rectified by modifying the pristine BC into engineered BC via multiple modification methods (physical, chemical, and mechanical), thus improving its decontamination functionalities. Recently, these engineered BCs/BC-based composites or BC composites have gathered pronounced attention for water decontamination due to fewer chemical requirements, high energy efficiency, and pollutant removal capacity. BC-based composites are synthesized by mixing BC with various modifiers, including carbonaceous material, clay minerals, metals, and metal oxides. They considerably modify the physiochemical attributes of BC and increase its adsorption ability against various types of aquatic pollutants. BC-based composites are efficient in eliminating target pollutants. The efficiency and type of a specific mechanism depend on various factors, mainly on the physicochemical characteristics and composition of the BC-based composites and the target pollutants. Among the different engineered BCs, the efficiency of clay-BC composites in removing the antibiotics, dyes, metals, and nutrients was good. This review could help develop a comprehensive understanding of using engineered BCs as effective materials for the remediation of contaminated water. Finally, gaps and challenges in research are identified, and future research needs are proposed.
An empirical study on technological innovation and corporate competitiveness of listed coal-to-liquids companies in China
Authors: Song Meihui , Wang Zhenqin , Wang Weicai
Published: November 2022

Technological innovation in the CTL1 industry is an important direction for China’s future development. Taking the China’s listed CTL companies as samples, this study makes an empirical test on the relationship between technological innovation capabilities and corporate competitiveness of CTL companies, and explores the regulating effect of enterprise scales on the relationship between technological innovation capabilities and corporate competitiveness, as well as the mediating effect of product differentiation on this relationship. It is found that the investment capacity of CTL enterprises for technological innovation has a significant driving effect on their competitiveness (with the correlation coefficient of 0.017), the output capacity of technological innovation has no remarkable effect on the promotion of the enterprises’ competitiveness (with the correlation coefficient of 0.0298), enterprise scales have a positive regulating effect on the relationship between technological innovation input and output capabilities and corporate competitiveness (with the coefficient of the interaction term of 0.3870 and 0.0002 respectively), and product differentiation plays a mediating effect on this relationship (with the coefficient of the interaction term of 0.147 and 0.096 respectively). From the results, it can be said that increasing R&D expenses of enterprises, encourage the cultivation and introduction of high-end R&D talents as well as strengthen technological innovation and enhance product differentiation can help to improve CTL enterprises’ competitiveness. The conclusions of this study can provide theoretical bases for CTL enterprises to hike and improve their competitiveness in terms of technological innovation.
Seabirds under environmental pressures: Food supplementation has a larger impact than selenium on chicks exposed to mercury and a viral disease
Authors: Sebastiano Manrico , Eens Marcel , Bustamante Paco , Chastel Olivier , Costantini David
Published: November 2022

Although infectious disease outbreaks represent a serious threat for wildlife population viability, the environmental factors that underlie such outbreaks are poorly investigated. The French Guiana breeding population of Magnificent frigatebird Fregata magnificens is subjected to recurrent episodes of chicks’ mortality likely caused by a viral disease. We hypothesized that high mercury (Hg) concentrations may be responsible for the emergence of clinical signs. We therefore investigated whether healthy and sick chicks show different Hg concentrations in blood. Because the essential element selenium (Se) may be highly depleted during Hg poisoning, we further experimentally tested whether an increased intake of dietary Se has an effect on blood levels of Hg, increases circulating Se, and improves the oxidative status of chicks. Finally, we compared the results of this experiment with a previous food supplementation experiment. Our results show similar Hg concentrations between healthy and sick chicks with visible clinical signs of the disease. Se concentrations were significantly depleted in sick chicks. Se concentrations increased while Hg concentrations simultaneously decreased in chicks that naturally recovered from the disease. Both the Se and fish supplementation experiments significantly increased Se concentrations in blood, while Hg levels were only modestly affected. Providing food to chicks appeared to have greater benefits than only supplementing chicks with Se pills as, although food supplementation had an impact on blood Se similar to that of supplementation with Se pills, it also reduced the vulnerability of chicks to the viral disease, possibly by reducing nutritional stress and providing essential nutrients.
From phenotypical investigation to RNA-sequencing for gene expression analysis: A workflow for single and pooled rare cells
Authors: Rossi Tania , Angeli Davide , Martinelli Giovanni , Fabbri Francesco , Gallerani Giulia
Published: November 2022

Combining phenotypical and molecular characterization of rare cells is challenging due to their scarcity and difficult handling. In oncology, circulating tumor cells (CTCs) are considered among the most important rare cell populations. Their phenotypic and molecular characterization is necessary to define the molecular mechanisms underlying their metastatic potential. Several approaches that require cell fixation make difficult downstream molecular investigations on RNA. Conversely, the DEPArray technology allows phenotypic analysis and handling of both fixed and unfixed cells, enabling a wider range of applications. Here, we describe an experimental workflow that allows the transcriptomic investigation of single and pooled OE33 cells undergone to DEPArray analysis and recovery. In addition, cells were tested at different conditions (unfixed, CellSearch fixative (CSF)- and ethanol (EtOH)-fixed cells). In a forward-looking perspective, this workflow will pave the way for novel strategies to characterize gene expression profiles of rare cells, both single-cell and low-resolution input.
Establishment of lung adenocarcinoma classification and risk model based on necroptosis-related genes
Authors: Wu Guodong , Feng Dingwei , Zhang Ziyu , Zhang Gao , Zhang Wei
Published: November 2022

Lung adenocarcinoma (LUAD) is the most widely known histological subtype of lung cancer. Its classification is significant for the characteristic evaluation of patients. The aim of this research is to assess the categorization of LUAD and its risk model based on necroptosis and to investigate its potential regulatory mechanisms for diagnosing and treating LUAD. According to the expression profile data along with the clinical information related to LUAD from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we constructed a consistency matrix through consistency clustering, and used the ConsensusClusterPlus as the measurement distance to cluster and subtype the samples, and performed gene set enrichment analysis and immune infiltration analysis. Least absolute shrinkage and selection operator (Lasso) regression was utilized for obtaining prognostic significant necroptosis phenotype-related genes. Finally, we measured each patient’s riskscore (RS) and build a risk model, and predicted the effect of immunotherapy for different groups of risk factors in the model. Three molecular subtypes of LUAD were obtained by cluster analysis of necroptosis-related genes in LUAD samples. Compared with C1, C3 had a better prognosis and higher immune cell infiltration. The prognosis of the C1 subtype was poor and had a high clinical grade. The proportion of Stage II, Stage III, and Stage IV was much more in comparison with that of the other two subtypes. TP53 gene had a high mutation frequency in the C1 subtype. Gene Set Enrichment Analysis (GSEA) indicated that the aberrant pathways in the C1 and C3 subtypes mainly included some cell cycle-related pathways. In addition, seven genes were identified as related genes of necroptosis phenotype affecting prognosis. High RS had a poor prognosis, while low RS had a good prognosis. The RS was verified to have a strong ability to predict survival. LUAD can be classified by the genes linked with cell necrosis and apoptosis. The difference among various types is helpful to deepen the understanding of LUAD. In addition, a risk model was constructed based. In conclusion, this study provides potential detection targets and treatment methods for LUAD from a new perspective.
A minimally-edited mouse model for infection with multiple SARS-CoV-2 strains
Authors: Nakandakari-Higa Sandra , Parsa Roham , Reis Bernardo S. , de Carvalho Renan V. H. , Mesin Luka , Hoffmann Hans-Heinrich , Bortolatto Juliana , Muramatsu Hiromi , Lin Paulo. J. C. , Bilate Angelina M. , Rice Charles M. , Pardi Norbert , Mucida Daniel , Victora Gabriel D. , Canesso Maria Cecilia C.
Published: November 2022

Efficient mouse models to study SARS-CoV-2 infection are critical for the development and assessment of vaccines and therapeutic approaches to mitigate the current pandemic and prevent reemergence of COVID-19. While the first generation of mouse models allowed SARS-CoV-2 infection and pathogenesis, they relied on ectopic expression and non-physiological levels of human angiotensin-converting enzyme 2 (hACE2). Here we generated a mouse model carrying the minimal set of modifications necessary for productive infection with multiple strains of SARS-CoV-2. Substitution of only three amino acids in the otherwise native mouse Ace2 locus (Ace2TripleMutant or Ace2™), was sufficient to render mice susceptible to both SARS-CoV-2 strains USA-WA1/2020 and B.1.1.529 (Omicron). Infected Ace2™ mice exhibited weight loss and lung damage and inflammation, similar to COVID-19 patients. Previous exposure to USA-WA1/2020 or mRNA vaccination generated memory B cells that participated in plasmablast responses during breakthrough B.1.1.529 infection. Thus, the Ace2™ mouse replicates human disease after SARS-CoV-2 infection and provides a tool to study immune responses to sequential infections in mice.
Oncolytic vaccinia virus expressing a bispecific T-cell engager enhances immune responses in EpCAM positive solid tumors
Authors: Wei Min , Zuo Shuguang , Chen Zhimin , Qian Peng , Zhang Yenan , Kong Lingkai , Gao Honglan , Wei Jiwu , Dong Jie
Published: November 2022

Insufficient intratumoral T-cell infiltration and lack of tumor-specific immune surveillance in tumor microenvironment (TME) hinder the progression of cancer immunotherapy. In this study, we explored a recombinant vaccinia virus encoding an EpCAM BiTE (VV-EpCAM BiTE) to modulate the immune suppressive microenvironment to enhance antitumor immunity in several solid tumors. VV-EpCAM BiTE effectively infected, replicated and lysed malignant cells. The EpCAM BiTE secreted from infected malignants effectively mediated the binding of EpCAM-positive tumor cells and CD3ϵ on T cells, which led to activation of naive T-cell and the release of cytokines, such as IFN-γ and IL-2. Intratumoral administration of VV-EpCAM BiTE significantly enhanced antitumor activity in malignancies with high other than with low EpCAM expression level. In addition, immune cell infiltration was significantly increased in TME upon VV-EpCAM BiTE treatment, CD8+ T cell exhaustion was reduced and T-cell-mediated immune activation was markedly enhanced. Taken together, VV-EpCAM BiTE sophistically combines the antitumor advantages of bispecific antibodies and oncolytic viruses, which provides preclinical evidence for the therapeutic potential of VV-EpCAM BiTE.
Waning of specific antibodies against Delta and Omicron variants five months after a third dose of BNT162b2 SARS-CoV-2 vaccine in elderly individuals
Authors: Goh Yun Shan , Rouers Angeline , Fong Siew-Wai , Zhuo Nicole Ziyi , Hor Pei Xiang , Loh Chiew Yee , Huang Yuling , Neo Vanessa Kexin , Kam Isaac Kai Jie , Wang Bei , Ngoh Eve Zi Xian , Salleh Siti Nazihah Mohd , Lee Raphael Tze Chuen , Pada Surinder , Sun Louisa Jin , Ong Desmond Luan Seng , Somani Jyoti , Lee Eng Sing ,   NCID Study Group,   COVID-19 Study Group, Maurer-Stroh Sebastian , Wang Cheng-I , Leo Yee‐Sin , Ren Ee Chee , Lye David C. , Young Barnaby Edward , Ng Lisa F. P. , Renia Laurent
Published: November 2022

The emergence of new SARS-CoV-2 variants, such as the more transmissible Delta and Omicron variants, has raised concerns on efficacy of the COVID-19 vaccines. Here, we examined the waning of antibody responses against different variants following primary and booster vaccination. We found that antibody responses against variants were low following primary vaccination. The antibody response against Omicron was almost non-existent. Efficient boosting of antibody response against all variants, including Omicron, was observed following a third dose. The antibody response against the variants tested was significantly higher at one month following booster vaccination, compared with two months following primary vaccination, for all individuals, including the low antibody responders identified at two months following primary vaccination. The antibody response, for all variants tested, was significantly higher at four months post booster than at five months post primary vaccination, and the proportion of low responders remained low (6-11%). However, there was significant waning of antibody response in more than 95% of individuals at four months, compared to one month following booster. We also observed a robust memory B cell response following booster, which remained higher at four months post booster than prior to booster. However, the memory B cell responses were on the decline for 50% of individuals at four months following booster. Similarly, while the T cell response is sustained, at cohort level, at four months post booster, a substantial proportion of individuals (18.8 – 53.8%) exhibited T cell response at four months post booster that has waned to levels below their corresponding levels before booster. The findings show an efficient induction of immune response against SARS-CoV-2 variants following booster vaccination. However, the induced immunity by the third BNT162b2 vaccine dose was transient. The findings suggest that elderly individuals may require a fourth dose to provide protection against SARS-CoV-2.
The Effect of immunotherapy on oligometastatic non-small cell lung cancer patients by sites of metastasis
Authors: Ma Jia-Chun , Zhang Jing-Xin , Wang Fei , Yu Jinming , Chen Dawei
Published: November 2022

Introduction

The efficacy of immunotherapy for treatment of patients with oligometastatic non-small cell lung cancer (NSCLC) at different metastatic sites remains controversial. We investigated the effect of different metastatic sites on immunotherapy for oligometastatic NSCLC following local treatment (LT).

Methods

We retrospectively analyzed patients with oligometastatic NSCLC from the latest 2018 registry on the SEER Stat software (8.3.9. Version) and a Chinese single-center cohort. The effects of immunotherapy on OS (overall survival) and CSS (cancer specific survival) were estimated for patients with different metastatic sites.

Results

A total of 483 patients in the SEER-18 database and 344 patients in the single-center cohort were included. Immunotherapy was significantly correlated with improved OS (SEER: Hazard ratio 0.754, 95% CI 0.609–0.932; P=0.044; China: Hazard ratio 0.697, 95% CI 0.542–0.896; P=0.005) and CSS (SEER: Hazard ratio 0.743, 95% CI 0.596–0.928; P=0.009; China: Hazard ratio 0.725, 95% CI 0.556–0.945; P=0.018). Subgroup analysis showed that OS was improved after immunotherapy in the BRM (SEER: Hazard ratio 0.565, 95% CI 0.385–0.829; P=0.004; China: Hazard ratio 0.536, 95% CI 0.312–0.920; P=0.024) and MOM (SEER: Hazard ratio 0.524, 95% CI 0.290–0.947; P=0.032; China: Hazard ratio 0.469, 95% CI 0.235–0.937; P=0.032) subgroups, but not in the BOM (SEER: P=0.334; China: P=0.441), LIM (SEER: P=0.301; China: P=0.357), or OTM (SEER: P=0.868; China: P=0.489) subgroups.

Conclusions

This study showed that immunotherapy conferred survival benefits on patients with oligometastatic NSCLC. Our subgroup analysis suggested that patients with oligometastatic NSCLC in the brain or multiple organs may particularly benefit from aggressive front-line therapies.
Characterization of immune checkpoint inhibitor-associated fulminant type 1 diabetes associated with autoantibody status and ethnic origin
Authors: Qiu Junlin , Luo Shuoming , Yin Wenfeng , Guo Keyu , Xiang Yufei , Li Xia , Liu Zhenqi , Zhou Zhiguang
Published: November 2022

Objective

Fulminant type 1 diabetes may uniquely occur as a fatal adverse event during immune checkpoint inhibitor (ICI) therapy. We investigated the clinical and immunological characteristics of ICI-associated fulminant type 1 diabetes (IFD).

Research design and methods

We enrolled 80 patients with IFD (77 cases from the literature), 56 patients with ICI-associated type 1 diabetes (IT1D) (55 cases from the literature), 45 patients with traditional fulminant type 1 diabetes (TFD), and 43 patients with acute-onset type 1 diabetes for comprehensive analysis including islet autoantibodies and subgroup analysis based on ethnic origin.

Results

Patients with IFD accounted for 58.8% (80/136) of patients with ICI-related diabetes. IFD had a more rapid onset than IT1D after ICI therapy (90.5 days vs. 120 days, p <0.05). The onset time and number of infusions after ICI therapy initiation were lower in the antibody-positive IFD group than that in the antibody-negative IFD group (both p <0.001). IFD had a more rapid onset and more serious among Caucasians than that among Asians (p <0.01, p <0.05, respectively), and the prevalence of islet autoantibody positivity in the Caucasian IFD were prominently higher than those in the Asian IFD (p <0.05). Onset age and plasma glucose levels were significantly higher in the IFD group than those in the TFD and acute-onset type 1 diabetes groups. HbA1c levels were slightly higher in patients with IFD than those with TFD.

Conclusions

IFD is relatively common in Caucasian population where TFD is very rare or almost absent. IFD occurrence is significantly related to islet autoantibody status and ethnic origin.
Hydrodynamic and sediment dynamic impact of human engineering activity on Liyashan oyster reefs, China
Authors: Luo Feng , Chen Zhipeng , Wu Hongbo , Zhu Fei , Zeng Jingwei , Quan Weimin
Published: November 2022

As human activity increases, coastal ecosystems are becoming increasingly vulnerable to a range of challenges. Oyster reefs are coastal ecosystems that provide habitats for a diverse range of marine species while also purifying water and providing natural coastal defense. However, because of human activity, global oyster reef areas have drastically diminished and are in grave danger. Simultaneously, it is impossible to determine the negative impact of human engineering activity on oyster reefs, due to the lack of intuitive and quantitative study methodologies. To address this issue, we applied a hydrodynamic model to analyze the impact on oyster reefs. First, we considered that human engineering activity, that is, coastal engineering, mainly affects the development of Liyashan Oyster Reefs by influencing hydrodynamics, sediment concentration, and bed-level evolution. We then applied MIKE3 to establish and validate a 3D hydrodynamic model of the southern part of the Yellow Sea around oyster reefs. Results showed that regional variations in flow velocity and suspended sediment concentration occurred in oyster reef waters, but the magnitude of these variations was limited. However, seabed elevation increased substantially in the Center Protection Area, which had a negative impact on oyster reefs. In general, our study provided a paradigm for analyzing the degree of impact on oyster reefs, showed the advantages of hydrodynamic models in quantitatively analyzing impact factors, and had reliable results.
The effect of body mass index on neonatal outcomes in Chinese women with polycystic ovary syndrome
Authors: Guo Haiyan , Wang Bian , Gao Hongyuan , Zhu Qianqian
Published: November 2022

Aim

This study aimed to explore the effect of body mass index (BMI) on neonatal outcomes in patients with polycystic ovary syndrome following the frozen embryo transfer (FET).

Methods

This study included 1,676 singletons born from mothers with polycystic ovary syndrome (PCOS) after FET between 1 Jan 2007 and 31 Dec 2019. BMI was categorized into three groups: underweight (BMI less than 18.5 kg/m2), normal weight (BMI between 18.5 and 24.9 kg/m2), and overweight (BMI between 25.0 and 29.9 kg/m2). Logistic regression models with generalized estimating equations were used for clustering by patients to explore the effect of BMI on neonatal outcomes.

Results

When compared to normal-weight mothers, the rate of large for gestational age (LGA) babies (adjusted odds ratio [aOR] 0.45, 95% confidence interval [95%CI] 0.22–0.93) significantly decreased for underweight mothers and significantly increased (aOR 1.82, 95%CI 1.38–2.41) for overweight mothers. The rate of high birth weight among infants from overweight mothers (aOR 1.75, 95%CI 1.15–2.65) was significantly higher than those from normal-weight mothers after adjusting for known confounding factors. The rate of small for gestational age (SGA) singleton (aOR 2.37, 95%CI 1.14–4.93) was lower among underweight mothers than normal-weight mothers.

Conclusion

Maternal underweight was a significant protective factor against LGA infants for singletons born from patients with PCOS after FET, whereas maternal overweight was an adverse factor for LGA infants.
Electron microscopy of desmosomal structures in the pemphigus human skin organ culture model
Authors: Radine Uta Katharina , Bumiller-Bini Hoch Valéria , Boldt Angelica B. Winter , Zillikens Detlef , Ludwig Ralf J. , Hammers Christoph M. , Klinger Matthias , Hundt Jennifer E.
Published: November 2022

Pemphigus is a chronic autoimmune skin blistering disease, characterized by acantholysis and by the production of autoantibodies directed against the structural desmosomal proteins desmoglein 1 (DSG1) and/or DSG3. Model systems allow the identification and testing of new therapeutic targets. Here, we evaluated ultrastructural desmosomal morphology in the human skin organ culture (HSOC) model injected with either anti-desmoglein (DSG) 1/3 single-chain variable fragment (scFv, termed Px4-3), Staphylococcus aureus exfoliative toxin (ETA) as a reference and positive control, and normal human IgG as a negative control. Each experimental condition was evaluated in abdominal skin biopsies from five different donors. After 24 h of incubation, we processed the samples for histological and ultrastructural electron microscopy analyses. We found that Px4-3 or ETA induced a loss of desmosomes and increased interdesmosomal widening, similar to patient skin biopsies and other pemphigus models. Thus, we propose the HSOC pemphigus model as an attractive tool to unravel novel therapeutic targets.
Different factors drive the assembly of pine and Panax notoginseng-associated microbiomes in Panax notoginseng-pine agroforestry systems
Authors: Jia Weijia , Wang Shu , He Xiahong , Zhao Xiaoyan
Published: November 2022

Land-use conversion affects the composition and assembly of plant-associated microbiomes, which in turn affects plant growth, development, and ecosystem functioning. However, agroforestry systems, as sustainable land types, have received little attention regarding the dynamics of different plant-associated microbes. In this study, we used high-throughput sequencing technology to analyze the assembly mechanisms and the driving factors of pine- and Panax notoginseng (P.n.)-associated microbiomes during the conversion of different pine forests (Pinus kesiya var. langbianensis and Pinus armandii) into P.n.-pine agroforestry systems. The results showed that the conversion of pure pine forest into P.n.-pine agroforestry systems significantly altered the diversity of pine-associated fungi rather than the community structure, and the community structure of P.n.-associated fungi rather than the diversity. Additionally, plant-associated fungi were more responsive to land-use change than bacteria. Main effect analysis revealed that compartment rather than genotype was the driving factor of pine- and P.n.-associated microbiomes, but P.n. cultivation also significantly affected the assembly of pine-associated microbiomes. In addition, there was a transfer of P.n. endophytes to pine trees in agroforestry systems and the beneficial microbiomes (Massilia, Marmoricola, Herbaspirillum, etc.) were enlarged in pine roots. Therefore, the diversity of the assembly mechanisms of P.n.- and pine-associated microbiomes played an important role in the P.n.--pine agroforestry systems and were the basis for the sustainable development of the P.n.--pine agroforestry systems.
Phyllosphere microbial community of cigar tobacco and its corresponding metabolites
Authors: Liu Tiantian , Guo Shiping , Wu Chongde , Zhang Ruina , Zhong Qiu , Shi Hongzhi , Zhou Rongqing , Qin Yanqing , Jin Yao
Published: November 2022

Cigar is made of a typical fermented tobacco where the microbiota inhabits within an alkaline environment. Our current understanding on cigar fermentation is far from thorough. This work employed both high-throughput sequencing and chromatography-mass spectrometric technologies to provide new scientific reference for this specific fermented system. Typical cigar samples from different regions (the Caribbeans, South America, East Asia, and Southeast Asia) were investigated. The results show that Firmicutes, Actinobacteria, Proteobacteria, Ascomycota, and Basidiomycota were the predominant phyla in the cigar samples. Rather than the fungal community, it was the bacterial community structures that played vital roles to differentiate the cigar from different regions: Staphylococcus was the dominant genus in the Americas; Bacillus was the dominant genus in Southeast Asia; while in East Asia, there was no dominant genus. Such differences in community structure then affected the microflora metabolism. The correlation between microbiota and metabolites revealed that Aspergillaceae, Cercospora, and Staphylococcus were significantly correlated with sclareolide; Bacillus were positively associated with isophorone. Alcaligenaceae was significantly and positively correlated with L-nicotine and hexadecanoic acid, methyl ester.

GRAPHICAL ABSTRACT
Computational approaches for network-based integrative multi-omics analysis
Authors: Agamah Francis E. , Bayjanov Jumamurat R. , Niehues Anna , Njoku Kelechi F. , Skelton Michelle , Mazandu Gaston K. , Ederveen Thomas H. A. , Mulder Nicola , Chimusa Emile R. , 't Hoen Peter A. C.
Published: November 2022

Advances in omics technologies allow for holistic studies into biological systems. These studies rely on integrative data analysis techniques to obtain a comprehensive view of the dynamics of cellular processes, and molecular mechanisms. Network-based integrative approaches have revolutionized multi-omics analysis by providing the framework to represent interactions between multiple different omics-layers in a graph, which may faithfully reflect the molecular wiring in a cell. Here we review network-based multi-omics/multi-modal integrative analytical approaches. We classify these approaches according to the type of omics data supported, the methods and/or algorithms implemented, their node and/or edge weighting components, and their ability to identify key nodes and subnetworks. We show how these approaches can be used to identify biomarkers, disease subtypes, crosstalk, causality, and molecular drivers of physiological and pathological mechanisms. We provide insight into the most appropriate methods and tools for research questions as showcased around the aetiology and treatment of COVID-19 that can be informed by multi-omics data integration. We conclude with an overview of challenges associated with multi-omics network-based analysis, such as reproducibility, heterogeneity, (biological) interpretability of the results, and we highlight some future directions for network-based integration.
Hypertriglyceridemia is associated with stroke after non-cardiac, non-neurological surgery in the older patients: A nested case-control study
Authors: Chen Chaojin , Wen Qianyu , Ma Chuzhou , Li Xiaoyue , Huang Tengchao , Ke Jie , Gong Chulian , Hei Ziqing
Published: November 2022

Introduction

Geriatric postoperative stroke is a rare but serious complication after surgery. The association between hypertriglyceridemia and postoperative stroke remains controversial, especially in older patients undergoing non-cardiac, non-neurological surgery. The study aims to address this clinical dilemma.

Materials and methods

We conducted a nested case-control study among 9601 aged patients undergoing non-cardiac non-neurological surgery from October 2015 to 2021. A total of 22 positive cases were matched for the surgical type and time, to 88 control patients by a ratio of 1:4. The effect of hypertriglyceridemia on the occurrence of postoperative stroke within 30 days after surgery was estimated using conditional logistic regression analysis by adjusting to various potential confounders.

Results

A total of 22 cases developed ischemia stroke after surgery, and compared with the non-stroke group, they had more postoperative ICU admission, longer postoperative hospitalization and higher total cost (all p < 0.05), and more patients were presenting with preoperative hypertriglyceridemia [8 (36.4%) vs. 15 (17.0%), p = 0.045]. There was a significant association between hypertriglyceridemia and postoperative stroke, with adjusted odds ratios of 6.618 (95% CI 1.286, 34.064) (p = 0.024). The above results remained robust in the sensitivity analyses.

Conclusion

Among older patients undergoing non-cardiac and non-neurological surgery, hypertriglyceridemia was associated with significant increased risk of postoperative stroke.
A novel truncating variant of SPAST associated with hereditary spastic paraplegia indicates a haploinsufficiency pathogenic mechanism
Authors: Nan Haitian , Chu Min , Liu Li , Xie Kexin , Wu Liyong
Published: November 2022

Introduction

Hereditary spastic paraplegias (HSPs) are genetic neurodegenerative diseases. The most common form of pure HSP that is inherited in an autosomal dominant manner is spastic paraplegia type 4 (SPG4), which is caused by mutations in the SPAST gene. Different theories have been proposed as the mechanism underlying SPAST-HSP for different types of genetic mutations, including gain- and loss-of-function mechanisms. To better understand the mutation mechanisms, we performed genetic analysis and investigated a truncating SPAST variant that segregated with disease in one family.

Objectives and methods

We described a pure HSP pedigree with family members across four generations. We performed genetic analysis and investigated a novel frameshift pathogenic variant (c.862_863dupAC, p. H289Lfs*27) in this family. We performed reverse transcription-polymerase chain reaction (RT-PCR), Sanger sequencing, and quantitative RT-PCR using total RNA from an Epstein-Barr virus-induced lymphoblastoid cell line produced from the proband. We also performed Western blotting on cell lysates to investigate if the protein expression of spastin is affected by this variant.

Results

This variant (c.862_863dupAC, p. H289Lfs*27) co-segregated with pure HSP in this family and is not registered in any public database. Measurement of SPAST transcripts in lymphoblasts from the proband demonstrated a reduction of SPAST transcript levels through likely nonsense-mediated mRNA decay. Immunoblot analyses demonstrated a reduction of spastin protein expression levels in lymphoblasts.

Conclusion

We report an SPG4 family with a novel heterozygous frameshift variant p.H289Lfs*27 in SPAST. Our study implies haploinsufficiency as the pathogenic mechanism for this variant and expands the known mutation spectrum of SPAST.
Visual function and disability are associated with microcystic macular edema, macular and peripapillary vessel density in patients with neuromyelitis optica spectrum disorder
Authors: Li Jin , Chen Yihong , Zhang Ying , He Zhiyong , Yu Huankai , Shi Ce , Shen Meixiao , Lu Fan
Published: November 2022

Purpose

To assess macular and peripapillary vessel density and neurodegeneration in eyes with and without microcystic macular edema (MME) in neuromyelitis optica spectrum disorder (NMOSD) patients while investigating their association with visual impairment and disease disability.

Methods

This is a cross-sectional study. A total of 52 eyes from 29 NMOSD patients were recruited, including 8 eyes with MME from 7 patients. Optical coherence tomography angiography (OCTA) images were analyzed to quantify the radial papillary capillary density (RPCD), and the density of macular microvascular network in both the superficial retinal capillary plexus (SRCP) and the deep retinal capillary plexus (DRCP). Thicknesses of the neural retinal layers centered on the fovea and the optic nerve head were also collected by OCT. Best-corrected visual acuity (BCVA) and Expanded Disability Status Scale (EDSS) scores were assessed for all patients. Microvascular densities and retinal sublayer thicknesses were compared among groups, and correlations of these vascular and structural parameters with BCVA and EDSS scores were determined.

Results

Patients with NMOSD and MME had significantly decreased visual acuity and worse EDSS score than patients without MME (P = 0.01 and 0.002, respectively). The vessel density in SRCP and RPCD were significantly lower in eyes with MME and ON compared to that of eyes with ON but without MME and eyes without MME or ON. Impairment of visual acuity and disease severity were significantly negatively associated with the reduction of SRCP vessel density and RPCD but were not related to DRCP vessel density.

Conclusions

MME were correlated with worse visual impairment and disability in NMOSD patients. Sparse SRCP vessel density and RPCD were observed in NMOSD MME eyes and correlated with worse BCVA and EDSS scores.
Case report: Recreational nitrous oxide abuse triggered peripheral neuropathy possibly through the immune-mediated pathogenesis
Authors: Dong Mei-Xue , Wang Qing , Xu Jun-Feng , Hu Ling , Yu Ying , Li Tao
Published: November 2022

Nitrous oxide (N2O), commonly known as laughing gas, is widely used in clinical practice and food industry. However, an increasing number of young people have been abusing N2O for recreational purpose, resulting in many functional disorders and sometimes irreversible nerve damage. We present the case of a 20-year-old N2O abuser who gradually developed peripheral neuropathy after continuously inhaling N2O for 2 months. The neurological symptoms of the patient had kept exacerbation for the next 2 months until she came for medical care sitting in a wheelchair. We suggested the patient halting N2O intake and supplementing methylcobalamine according to the standardized protocol. Her symptoms had partly recovered during the following 2 weeks but remained unchanged in another 2 weeks. Antibodies against ganglioside complexes were detected and anti-GM1 IgM antibodies were positive in both cerebrospinal fluid and serum. Intravenous immunoglobulin was given as an additional treatment and the patient's symptoms had significantly recovered further. The patient discharged walking by herself. Then she has been continuously followed up in outpatient department for the next 4 months and taking steroid hormone as well as methylcobalamine. Her symptoms gradually disappeared and all the electrophysiological parameters significantly improved. With this case we were able to show that N2O-related peripheral neuropathy is not only a metabolic disorder but also an immune-mediated disease. N2O intake can trigger a mimic Guillain-Barré syndrome.