bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary copper intake and risk of myocardial infarction in US adults: A propensity score-matched analysis
Authors: Wen He , Niu Xiaona , Hu Lang , Sun Nan , Zhao Ran , Wang Qiuhe , Li Yan
Published: November 2022

Objectives

Most studies have examined the association between serum copper and myocardial infarction, but there is little evidence of the association between dietary copper intake and myocardial infarction.

Materials and methods

The study included a total of 14,876 participants from the 2011 to 2018 National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression model was used to analyze the association between dietary copper intake and the risk of myocardial infarction. To reduce selection bias, we use nearest neighbor propensity score matching (PSM) in a 1:2 ratio. Restricted cubic spline (RCS) method is used to study the non-linear relationship. Subgroup stratification was used to further investigate the association between copper intake and myocardial infarction.

Results

The median dietary copper intake was 1.0825 mg/day. A myocardial infarction had occurred in approximately 4.4% (655) of the participants. Before and after matching, multivariate logistic regression models revealed a negative correlation between dietary copper intake and the risk of myocardial infarction. The higher quartile of subjects had a noticeably lower risk of myocardial infarction in comparison to those in the first quartile of copper intake. According to RCS findings, dietary copper intake and myocardial infarction have a non-linear and dose-response relationship. According to stratified analysis, the dietary copper intake was a substantial protective element for those who were ≥ 50 years old, female, 25 ≤BMI <30, with history of smoking, hypertension, diabetes and ortholiposis.

Conclusion

Increased dietary copper intake was associated with a lower risk of myocardial infarction. It is especially significant in elderly-aged women, overweight individuals, smokers, hypertension, and diabetic patients.
Development and validation of a predictive model of the impact of single nucleotide polymorphisms in the ICAM-1 gene on the risk of ischemic cardiomyopathy
Authors: Naman Tuersunjiang , Abuduhalike Refukaiti , Yakufu Mubalake , Bawudun Ayixigu , Sun Juan , Mahemuti Ailiman
Published: November 2022

Objective

Previous research has linked single nucleotide polymorphisms (SNPs) in the ICAM-1 gene to an increased risk of developing ischemic cardiomyopathy (ICM); however, a diagnostic model of ICM according to the ICAM-1 variant has not yet been developed. Therefore, this study aimed to explore the correlation between SNPs in ICAM-1 and the presence of ICM, along with developing a diagnostic model for ICM based on the variants of the ICAM-1 gene.

Method

This study recruited a total of 252 patients with ICM and 280 healthy controls. In addition, all the participants were genotyped for SNPs in the ICAM-1 gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Using the training dataset of 371 people, we constructed a nomogram model based on ICAM-1 gene variants and clinical variables. To optimize the feature choice for the ICM risk model, a least absolute shrinkage and selection operator (LASSO) regression model was adopted. We also employed multivariable logistic regression analysis to build a prediction model by integrating the clinical characteristics chosen in the LASSO regression model. Following the receiver operating characteristic (ROC), a calibration plot and decision curve analysis (DCA) were used to evaluate the discrimination, calibration, and clinical usefulness of the predictive model.

Result

The predictors involved in the prediction nomogram included age, smoking, diabetes, low-density lipoprotein-cholesterol, hemoglobin, N-terminal pro-B-type natriuretic peptide, ejection fraction, and the rs5491 SNP. The nomogram model exhibited good discrimination ability, with the AUC value of ROC of 0.978 (95%CI: 0.967–0.989, P < 0.001) in the training group and 0.983 (95% CI: 0.969–0.998, P < 0.001) in the validation group. The Hosmer–Lemeshow test demonstrated good model calibration with consistency (Ptraining group = 0.937; Pvalidation group = 0.910). The DCA showed that the ICM nomogram was clinically beneficial, with the threshold probabilities ranging from 0.0 to 1.0.

Conclusion

The AT genotype in rs5491 of the ICAM-1 gene was associated with having a higher frequency of ICM. Individuals carrying the mutant AT genotype showed a 5.816-fold higher frequency of ICM compared with those with the AA genotype. ICM patients with the AT genotype also had a higher rate of cardiogenic death. We, therefore, developed a nomogram model that could offer an individualized prediction of ICM risk factors.
Significant risk of COVID-19 and related-hospitalization among patients with adrenal insufficiency: A large multinational survey
Authors: Yedinak Christine , Ross Ian Louis
Published: November 2022

Objective

To determine self-reported incidence and potential risk factors for COVID-19 in patients with adrenal insufficiency (AI).

Methods

A 27-item AI survey was developed for AI and COVID-19 status, vetted by specialists and patients, and distributed via social media, websites, and advocacy groups. Participation was voluntary and anonymous. Data were collected from September 20th, 2020 until December 31st, 2020.

Results

Respondents (n=1291) with self-reported glucocorticoid treatment for AI, completed the survey, with 456 who reported having symptoms and were screened for COVID-19 during 2020; 40 tested positive (+ve), representing an 8.8% incidence. Of the COVID-19+ve, 31 were female (78%), with mean age of 39.9 years. COVID-19 among AI patients occurred most commonly in those aged 40–59 years (n=17; 42.5%); mean time since AI diagnosis was 13.5 years (range 0.2−42.0 years). Pulmonary disease, congenital adrenal hyperplasia, and higher maintenance doses of glucocorticoids were significantly associated with +ve COVID-19 (p=0.04, p=0.01, and p=0.001, respectively. In respondents the cumulative incidence of COVID-19+ve during 2020 was 3.1%; greater than the 1.03% worldwide-incidence reported by WHO, by December 31st, 2020. There was a 3-fold (95% CI 2.16-3.98) greater relative risk (RR) of COVID-19 infection and a 23.8- fold (95% CI 20.7-31.2) RR of hospitalization in patients with AI, compared with the global population.

Conclusion

A markedly raised RR of COVID-19 and hospitalization in respondents reporting chronic AI was detected. We found that a diagnosis of congenital adrenal hyperplasia, age>40 years, male gender, pulmonary disease, and higher maintenance doses of glucocorticoids were associated with greatest risk.
Study on factors affecting vertical drilling bottom hole assembly performance and a new bottom hole assembly design method considering formation uncertainties
Authors: Xi Chuanming , Zhang Wei , Zhang Nan , Chu Hengzhi
Published: November 2022

Drilling a deep vertical well at a low cost is very important for accelerating the exploration and development of oil and gas resources. Vertical drilling BHA design is the key to drill a vertical well, however the BHA design is still an art not science in some formation. In this paper, a new mechanical model of bent-housing motor BHA is established, a build rate prediction method considering formation properties is presented and a BHA design method considering formation uncertainties is proposed. The evaluation results of vertical drilling BHA show that formation dip, formation anisotropy and hole diameter expansion are the main factors affecting pendulum BHA performance, and formation dip, formation anisotropy, hole diameter expansion and the distance from the upper stabilizer to the bit are the main factors affecting bent-housing motor BHA performance. The case study of the proposed BHA design method demonstrates that hole diameter expansion is very important for vertical drilling BHA performance, and should be taken in to account during the design process. The models and method proposed in this paper is helpful in maintaining verticality and reduce drilling cost.
The research on spatial-temporal evolution and influence factors of urban resilience: A case study in the Guangzhou metropolitan area
Authors: Tang Bo , Tan Zechuang
Published: November 2022

Resilience city, a new concept of city sustainable development, becomes one of the important subjects of high-quality development research. Compared to the traditional urban disaster mitigation approach, resilient cities focus more on the organizational capacity and coordination within the urban systems. Taking Guangzhou metropolitan area as an instance, which is featured a highly developed economy and society and frequently happened hazards and disturbances, the paper constructs an evaluation index system from four city subsystems, including economy, society, ecology, and engineering. Meanwhile, by applying the methods of global entropy weight, variation coefficient, geographic information system, and obstacle degree model, the paper explores the time changes, space evolution, and obstacle degree factors of city resilience in the Guangzhou metropolitan area from 2010 to 2020. The research results show that: (1) There is a significant change in the time difference of city comprehensive resilience of the Guangzhou metropolitan area. The resilience of each city’s resilience subsystem has grown steadily, of which the development level of economic resilience, social resilience, and engineering resilience has been steadily improved, and ecology resilience level shows a slight decline among a steadily increasing. (2) The overall city resilience of the Guangzhou metropolitan area shows a radial pattern taking Guangzhou as the core, of which the city economy, society, and engineering resilience grades mainly show a medium and low resilience level, the ecology resilience mainly shows a medium and high resilience level, and the general performance of resilience space distribution level is high in the southeast and low in the northwest. (3) Social resilience and ecological resilience are the main driving subsystems in the early and late stages of city resilience development in Guangzhou metropolitan area during the research period, and engineering resilience is the main constraint subsystem. (4) Water and soil loss control area and population density are the main obstacle factors in the early and late stages of city resilience in the Guangzhou metropolitan area. The density of the city drainage pipeline and the total import and export volume are the basic resilience barrier factors. The paper analyzes the spatial-temporal pattern and influencing factors of city resilience in the metropolitan area from a multi-dimensional perspective, provides a new thinking and analysis framework for the management and sustainability of city resilience in the metropolitan area, and provides a reference for the coordinated development of the metropolitan area.
Phylogenetic relationship and taxonomic status of Gymnocypris eckloni (Schizothoracinae) based on specific locus amplified fragments sequencing
Authors: Wanghe Kunyuan , Feng Chenguang , Tang Yongtao , Qi Delin , Ahmad Shahid , Nabi Ghulam , Li Xiaohui , Wang Guojie , Jian Longsheng , Liu Sijia , Zhao Kai , Tian Fei
Published: November 2022

Accurately delimiting phylogenetic relationships and taxonomic status is important for understanding species diversity and distributions and devising effective strategies for biodiversity conservation. However, species delimitation is controversial in Gymnocypris eckloni, a schizothoracine fish endemic to the Qinghai–Tibetan Plateau. The aim of this study is robustly identifying the phylogeny of G. eckloni in the Yellow River (YR) population and Qaidam basin (QB) population. The specific-locus amplified fragments sequencing (SLAF-seq) is employed with comprehensively sampling of schizothoracine fishes. In total, 350,181,802 clean reads and 5,114,096 SNPs are identified from SLAF-seq. Phylogenetic analysis recovers a non-monophyletic population of G. eckloni between YR and QB populations, representing an independent phylogenetic relationship between the two populations. Species delimitation analyses by SNAPPER and GMYC methods using the genome-wide SNP data confirm that their taxonomic statuses are separated. This study highlights the importance of further reconsidering clearer taxonomy, which would improve the genetic diversity conservation of Tibetan highland fishes.
Low expression of INMT is associated with poor prognosis but favorable immunotherapy response in lung adenocarcinoma
Authors: Zhou Xincheng , Zou Bing , Wang Jian , Wu Lihong , Tan Qiang , Ji Chunyu
Published: November 2022

Background: The expression of INMT (indolethylamine N-methyltransferase) has been reported to be downregulated in non-small-cell lung cancer (NSCLC). However, the role of INMT in NSCLC remains elusive. We aim to investigate the underlying mechanisms and clinical value of INMT in NSCLC, especially in lung adenocarcinoma (LUAD).

Methods: Gene expression cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to assess the effect of INMT on NSCLC. Gene expression data from an immunotherapy cohort were used to investigate the association of INMT with immunotherapy in NSCLC.

Results: INMT expression was significantly downregulated in NSCLC compared with adjacent normal tissues. Downregulated INMT was associated with poor overall survival in LUAD, but not in lung squamous carcinoma. Multivariate Cox regression analysis suggested that INMT was an independent prognostic marker in LUAD. INMT had a reference value in the diagnosis and prognostic estimation of LUAD. Gene set enrichment analysis showed that pathways of the cell cycle and DNA damage response were enriched in the INMT low-expression group. The top 10 hub genes upregulated in the INMT low-expression group mainly activated the cell cycle pathway. In addition, more frequently mutated TP53 genes, higher aneuploidy scores, a fraction of genomes altered, MANTIS scores, and tumor mutation burden were found in tumors with low expression of INMT. Furthermore, patients with low expression of INMT showed favorable clinical benefits to anti-PD-1 treatment with higher enrichment scores of immune-related signatures.

Conclusion: The low expression of INMT was associated with poor prognosis but favorable immunotherapy response in LUAD. INMT may affect the progression of LUAD by regulating the cell cycle and may serve as a valuable independent prognostic biomarker in patients with LUAD.
Clinical exome-based panel testing for medically actionable secondary findings in a cohort of 383 Italian participants
Authors: Martone Stefania , Buonagura Autilia Tommasina , Marra Roberta , Rosato Barbara Eleni , Del Giudice Federica , Bonfiglio Ferdinando , Capasso Mario , Iolascon Achille , Andolfo Immacolata , Russo Roberta
Published: November 2022

Background: Next-generation sequencing-based genetic testing represents a great opportunity to identify hereditary predispositions to specific pathological conditions and to promptly implement health surveillance or therapeutic protocols in case of disease. The term secondary finding refers to the active search for causative variants in genes associated with medically actionable conditions.

Methods: We evaluated 59 medically actionable ACMG genes using a targeted in silico analysis of clinical exome sequencing performed in 383 consecutive individuals referred to our Medical Genetics Unit. A three-tier classification system of SFs for assessing their clinical impact and supporting a decision-making process for reporting was established.

Results: We identified SFs with high/moderate evidence of pathogenicity in 7.0% (27/383) of analyzed subjects. Among these, 12/27 (44.4%) were carriers of a high-risk recessive disease allele. The most represented disease domains were cancer predisposition (33.3%), cardiac disorders (16.7%), and familial hypercholesterolemia (12.5%).

Conclusion: Although still debated, ensuring during NGS-based genetic testing an opportunistic screening might be valuable for personal and familial early management and surveillance of medically actionable disorders, the individual’s reproductive choices, and the prevalence assessment of underestimated hereditary genetic diseases.
Ovarian cancer stem cells: Critical roles in anti-tumor immunity
Authors: Ding Jing , Zhang Yan , Che Yan
Published: November 2022

Ovarian cancer is a significant cause of cancer-related mortality in women. Over the past 3 decades, there has been a high incidence of recurrent chemoresistant disease, despite the relative effectiveness of current treatment strategies. This is partly attributed to cancer stem cells (CSC), a subpopulation that has acquired stem cell properties that allow these cells to evade standard chemotherapy and cause disease recurrence. Therefore, there is an urgent need for basic knowledge about CSC to develop innovative therapeutic approaches for ovarian cancer. These CSC subpopulations have been identified in ovarian cancer cell lines, tumors or ascites, and findings suggest that ovarian CSCs may be as heterogeneous as the disease itself. CSCs regulate the phenotype and function of immune cells involved in antitumor immunity, so a better understanding of the signaling pathways that interact between CSCs, immune cells and tumor cells will pave the way for the clinical application of CS in cancer immunotherapy. This review will focus on the markers currently used to identify and isolate these cells summarize current knowledge on the molecular and cellular mechanisms responsible for CSC-dependent regulation of antitumor immune responses. We will discuss the signaling pathways involved in CSC survival, replication, and differentiation as well as potential therapeutic targeting strategies.
Health professionals' perspectives on clinical challenges in managing hypertensive disorders of pregnancy and recommendations for improving care: A multi-center qualitative study
Authors: Adu-Bonsaffoh Kwame , Tamma Evelyn , Nwameme Adanna Uloaku , Browne Joyce L.
Published: November 2022

Background

Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal mortality and morbidity globally despite the intensive international effort to improving maternal care. Substandard clinical care has emerged as a major contributing factor to the high maternal deaths associated with maternal hypertension globally and the impact is severer in low- and middle-income countries (LMICs). Context specific challenges impact negatively on the quality of maternity care and health providers play a crucial role in achieving positive pregnancy experiences for women. This study explored the perspectives of health professionals on the clinical challenges associated with the management of HDP in Ghana and recommendations for improving care.

Methods

A multi-center qualitative study using in-depth interviews (IDIs) was conducted in five major hospitals in the Greater Accra Region of Ghana between June 2018 and March 2019. Health professionals (midwives/nurses and medical doctors) who have worked at the study sites for at least three months were included. Data were analysed based on thematic content using Nvivo software.

Results

We included 62 health professionals comprising 40 midwives/nurses (64.5%) with a median age of 32.5 years (range 26 to 59) and 22 medical doctors (34.5%) with a median age of 34 years (range 25 to 55). Health providers highlighted major challenges associated with clinical management of hypertension in pregnancy: (1) patient-related factors (inadequate understanding and misconceptions about hypertension in pregnancy, women's non-compliance with clinical advice, financial constraints); (2) health system-related challenges (frequent unavailability of logistics, medications and laboratory support, delays in provision of care and limitations in the health insurance coverage); (3) health provider associated factors (inadequate number of health professionals and poor attitudes). Context-specific recommendations suggested for improving the quality of care in managing maternal hypertension include restructuring of the health system to reduce delays in providing care, improving financial coverage of medical insurance, encouraging social/family support, enhancing education on HDP and strengthening the health workers’ numbers and working conditions.

Conclusion

Major challenges in the clinical management of HDP relate to the health system, health professionals and pregnant women themselves. Context-specific interventions are required to improve the quality of care for hypertensive mothers including regular health education, re-structuring of the health systems, refresher courses for health providers, improvement in health insurance coverage and government subsidy for hypertensive women.
A subtractive proteomics approach for the identification of immunodominant Acinetobacter baumannii vaccine candidate proteins
Authors: Acar Mustafa Burak , Ayaz-Güner Şerife , Güner Hüseyin , Dinç Gökçen , Ulu Kılıç Ayşegül , Doğanay Mehmet , Özcan Servet
Published: November 2022

Background

Acinetobacter baumannii is one of the most life-threatening multidrug-resistant pathogens worldwide. Currently, 50%–70% of clinical isolates of A. baumannii are extensively drug-resistant, and available antibiotic options against A. baumannii infections are limited. There is still a need to discover specific de facto bacterial antigenic proteins that could be effective vaccine candidates in human infection. With the growth of research in recent years, several candidate molecules have been identified for vaccine development. So far, no public health authorities have approved vaccines against A. baumannii.

Methods

This study aimed to identify immunodominant vaccine candidate proteins that can be immunoprecipitated specifically with patients’ IgGs, relying on the hypothesis that the infected person’s IgGs can capture immunodominant bacterial proteins. Herein, the outer-membrane and secreted proteins of sensitive and drug-resistant A. baumannii were captured using IgGs obtained from patient and healthy control sera and identified by Liquid Chromatography- Tandem Mass Spectrometry (LC-MS/MS) analysis.

Results

Using the subtractive proteomic approach, we determined 34 unique proteins captured only in drug-resistant A. baumannii strain via patient sera. After extensively evaluating the predicted epitope regions, solubility, transverse membrane characteristics, and structural properties, we selected several notable vaccine candidates.

Conclusion

We identified vaccine candidate proteins that triggered a de facto response of the human immune system against the antibiotic-resistant A. baumannii. Precipitation of bacterial proteins via patient immunoglobulins was a novel approach to identifying the proteins that could trigger a response in the patient immune system.
IgA in human health and diseases: Potential regulator of commensal microbiota
Authors: Takeuchi Tadashi , Ohno Hiroshi
Published: November 2022

Gut microbiota has extensive and tremendous impacts on human physiology and pathology. The regulation of microbiota is therefore a cardinal problem for the mutualistic relationship, as both microbial overgrowth and excessive immune reactions toward them could potentially be detrimental to host homeostasis. Growing evidence suggests that IgA, the most dominant secretory immunoglobulin in the intestine, regulates the colonization of commensal microbiota, and consequently, the microbiota-mediated intestinal and extra-intestinal diseases. In this review, we discuss the interactions between IgA and gut microbiota particularly relevant to human pathophysiology. We review current knowledge about how IgA regulates gut microbiota in humans and about the molecular mechanisms behind this interaction. We further discuss the potential role of IgA in regulating human diseases by extrapolating experimental findings, suggesting that IgA can be a future therapeutic strategy that functionally modulates gut microbiota.
Sebaceous immunobiology - skin homeostasis, pathophysiology, coordination of innate immunity and inflammatory response and disease associations
Authors: Zouboulis Christos C. , Coenye Tom , He Li , Kabashima Kenji , Kobayashi Tetsuro , Niemann Catherin , Nomura Takashi , Oláh Attila , Picardo Mauro , Quist Sven R. , Sasano Hironobu , Schneider Marlon R. , Törőcsik Daniel , Wong Sunny Y.
Published: November 2022

This review presents several aspects of the innovative concept of sebaceous immunobiology, which summarizes the numerous activities of the sebaceous gland including its classical physiological and pathophysiological tasks, namely sebum production and the development of seborrhea and acne. Sebaceous lipids, which represent 90% of the skin surface lipids in adolescents and adults, are markedly involved in the skin barrier function and perifollicular and dermal innate immune processes, leading to inflammatory skin diseases. Innovative experimental techniques using stem cell and sebocyte models have clarified the roles of distinct stem cells in sebaceous gland physiology and sebocyte function control mechanisms. The sebaceous gland represents an integral part of the pilosebaceous unit and its status is connected to hair follicle morphogenesis. Interestingly, professional inflammatory cells contribute to sebocyte differentiation and homeostasis, whereas the regulation of sebaceous gland function by immune cells is antigen-independent. Inflammation is involved in the very earliest differentiation changes of the pilosebaceous unit in acne. Sebocytes behave as potent immune regulators, integrating into the innate immune responses of the skin. Expressing inflammatory mediators, sebocytes also contribute to the polarization of cutaneous T cells towards the Th17 phenotype. In addition, the immune response of the perifollicular infiltrate depends on factors produced by the sebaceous glands, mostly sebaceous lipids. Human sebocytes in vitro express functional pattern recognition receptors, which are likely to interact with bacteria in acne pathogenesis. Sex steroids, peroxisome proliferator-activated receptor ligands, neuropeptides, endocannabinoids and a selective apoptotic process contribute to a complex regulation of sebocyte-induced immunological reaction in numerous acquired and congenital skin diseases, including hair diseases and atopic dermatitis.
Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies
Authors: Singh Harjeet , Srour Samer A. , Milton Denái R. , McCarty Jessica , Dai Cuiping , Gaballa Mahmoud R. , Ammari Mariam , Olivares Simon , Huls Helen , De Groot Eleanor , Marin David , Petropoulos Demetrios , Olson Amanda L. , Anderlini Paolo , Im Jin S. , Khouri Issa , Hosing Chitra M. , Rezvani Katayoun , Champlin Richard E. , Shpall Elizabeth J. , Cooper Laurence J. N. , Kebriaei Partow
Published: November 2022

Chimeric antigen receptor (CAR) T-cell therapy has emerged recently as a standard of care treatment for patients with relapsed or refractory acute lymphoblastic leukemia (ALL) and several subtypes of B-cell non-Hodgkin lymphoma (NHL). However, its use remains limited to highly specialized centers, given the complexity of its administration and its associated toxicities. We previously reported our experience in using a novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy in the peri-transplant setting, where it exhibited an excellent safety profile with encouraging survival outcomes. We have since modified the SB CD19 CAR construct to improve its efficacy and shorten its manufacturing time. We report here the phase 1 clinical trial safety results. Fourteen heavily treated patients with relapsed/refractory ALL and NHL were infused. Overall, no serious adverse events were directly attributed to the study treatment. Three patients developed grades 1-2 cytokine release syndrome and none of the study patients experienced neurotoxicity. All dose levels were well tolerated and no dose-limiting toxicities were reported. For efficacy, 3 of 8 (38%) patients with ALL achieved CR/CRi (complete remission with incomplete count recovery) and 1 (13%) patient had sustained molecular disease positivity. Of the 4 patients with DLBCL, 2 (50%) achieved CR. The SB-based CAR constructs allow manufacturing of targeted CAR T-cell therapies that are safe, cost-effective and with encouraging antitumor activity.
Toxicity profile of combined immune checkpoint inhibitors and thoracic radiotherapy in esophageal cancer: A meta-analysis and systematic review
Authors: Xu Tongzhen , Liu Yunsong , Lu Xiaotong , Liang Jun
Published: November 2022

Background

Therapies based on the combination of immune checkpoint inhibitors (ICIs) and thoracic radiotherapy (TRT) are transforming the treatment landscape of esophageal cancer. Nevertheless, the available data on adverse events (AEs) mainly stemmed from several prospective clinical trials and retrospective studies, in which, AE data are often handled and reported with less rigor than the primary beneficial outcomes of the study. Thus, we conducted a systematic review to investigate the toxicity spectrum of these novel regimens.

Method

We searched for all prospective clinical trials investigating the role of ICIs combined with TRT published between January 2010 and August 2022. Study articles and conference proceedings involving esophageal cancers and reporting the overall incidence or details of treatment-related AEs (trAEs) were synthesized to determine the toxicity profile of combination treatment. We compared trAEs between cancer type, programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, and between sequential and concurrent administration of ICIs and TRT to identify potentially high-risk patients.

Results

We obtained toxicity data from 14 clinical trials involving 863 patients. The pooled overall incidence was 88.97% for any-grade trAEs and 18.48% for high-grade trAEs. The three most frequent non-hematologic any-grade trAEs were reactive cutaneous capillary endothelial proliferation (RCCEP, 63.80%), esophagitis (51.54%), and fatigue (33.63%). Meanwhile, RCCEP (15.69%) was the most common non-hematologic high-grade trAE, followed by nausea (4.91%) and anorexia (3.81%). The occurrence rates of any-grade and high-grade pneumonitis were 10.82% and 0.66%, respectively. In subgroup analysis, the toxicity profiles of PD-1 and PD-L1 inhibitors were mostly similar, except for any-grade pneumonitis (15.20% vs 4.88%, p=0.03) and high-grade leukopenia (6.25% vs 59.09%, p=0.00). In addition, concurrent treatment seemed to have a higher incidence of any-grade trAEs (95.20% vs 70.85%, p=0.03) compared with sequential treatment. ESCC seems to have higher incidence of any-grade hypothyroidism (22.55% vs 8.96%, p=0.049) compared to EAC.

Conclusion

Our study is the first systematic review to provide a toxicity profile of trAEs in esophageal cancer patients who received ICIs combined with TRT. Most AEs of this combination treatment are tolerable, although the incidence of any-grade trAEs was higher in the concurrent group. The difference in any-grade pneumonitis between PD-1 and PD-L1 inhibitor groups needs further validation in a large clinical trial.
A randomized controlled trial to verify the irrigation of salivary glands in relieving xerostomia in patients with Sjögren’s syndrome
Authors: Du Hongming , Fu Zhen , Zhong Yi , Yuan Yi , Zhao Jing , Ding Xu , Li Sheng , Gao Shiyu , Zhu Yuchi , Song Haiyang , Wu Heming
Published: November 2022

Objective

To verify the effect of triamcinolone acetonide (TA) and major salivary glands saline irrigation on relieving xerostomia in Sjögren’s syndrome (SS) patients.

Methods

The enrolled 49 SS patients were randomly assigned to the control group (no irrigation, n=16), saline group (irrigation with saline, n=17) and TA group (irrigation with TA, n=16). Fourteen cases of each group were treated differently but received the same examinations. The examinations include unstimulated whole saliva flow (UWS), chewing-stimulated whole saliva flow (SWS), citric acid-stimulated parotid flow (SPF), Clinical Oral Dryness Score (CODS), Xerostomia Inventory (XI) and EULAR SS Patient Reported Index (ESSPRI) of 1 week before irrigation (T0) and 1 week(T1), 8 weeks (T8), 16 weeks (T16) and 24 weeks (T24) after major salivary irrigation.

Results

Each group had 14 cases with completed follow-ups. Both TA and saline irrigation of major salivary glands resulted in higher SWS and SPF of T8, T16 and than those at T0. ESSPRI (oral dryness domain) of T8, T16 and T24 were significantly lower than that at T0, respectively (P < 0.05). SWS and SPF of T8, T16 and T24 in the saline group were significantly higher than in the control group (P< 0.05). XI and ESSPRI (oral dress domain) of T8, T16 and T24 in the saline group were significantly lower than those in the control group, respectively (P< 0.05). SWS and SPF of T16 and T24 in the TA group were significantly higher than in the control group (P< 0.05). All cases with completed follow-up in TA and saline groups were divided into responders and non-responders. Compared with responders, the UWS, SWS, SPF and CODS of T0 in non-responders were significantly increased (P<0.05). Compared with responders, the XI and ESSPRI of T0 in non-responders were significantly decreased (P<0.05).

Conclusion

The irrigation of major salivary glands by TA and saline relieve xerostomia in SS patients. Patients with non-severe xerostomia (responders) have better relief after irrigation than patients with severe xerostomia (non-responders).

Clinical Trial Registration

www.chictr.org.cn, identifier (ChiCTR210052314).
Current status and development prospects of aquatic vaccines
Authors: Du Yang , Hu Xiaoman , Miao Liang , Chen Jiong
Published: November 2022

Diseases are a significant impediment to aquaculture’s sustainable and healthy growth. The aquaculture industry is suffering significant financial losses as a result of the worsening water quality and increasing frequency of aquatic disease outbreaks caused by the expansion of aquaculture. Drug control, immunoprophylaxis, ecologically integrated control, etc. are the principal control strategies for fish infections. For a long time, the prevention and control of aquatic diseases have mainly relied on the use of various antibiotics and chemical drugs. However, long-term use of chemical inputs not only increases pathogenic bacteria resistance but also damages the fish and aquaculture environments, resulting in drug residues in aquatic products, severely impeding the development of the aquaculture industry. The development and use of aquatic vaccines are the safest and most effective ways to prevent aquatic animal diseases and preserve the health and sustainability of aquaculture. To give references for the development and implementation of aquatic vaccines, this study reviews the development history, types, inoculation techniques, mechanisms of action, development prospects, and challenges encountered with aquatic vaccines.
Research progress on anti-ovarian cancer mechanism of miRNA regulating tumor microenvironment
Authors: Cui MingHua , Liu YueHui , Cheng Li , Li Tao , Deng YongZhi , Liu Da
Published: November 2022

Ovarian cancer is the most deadly malignancy among women, but its complex pathogenesis is unknown. Most patients with ovarian cancer have a poor prognosis due to high recurrence rates and chemotherapy resistance as well as the lack of effective early diagnostic methods. The tumor microenvironment mainly includes extracellular matrix, CAFs, tumor angiogenesis and immune-associated cells. The interaction between tumor cells and TME plays a key role in tumorigenesis, progression, metastasis and treatment, affecting tumor progression. Therefore, it is significant to find new tumor biomarkers and therapeutic targets. MicroRNAs are non-coding RNAs that post-transcriptionally regulate the expression of target genes and affect a variety of biological processes. Studies have shown that miRNAs regulate tumor development by affecting TME. In this review, we summarize the mechanisms by which miRNAs affect ovarian cancer by regulating TME and highlight the key role of miRNAs in TME, which provides new targets and theoretical basis for ovarian cancer treatment.
The potential economic benefits of insect-based feed in Uganda
Authors: Abro Zewdu , Macharia Ibrahim , Mulungu Kelvin , Subramanian Sevgan , Tanga Chrysantus Mbi , Kassie Menale
Published: November 2022

Black soldier fly farming is gaining traction globally as a strategy for recycling organic waste into high-quality proteins and fat for feed and organic fertilizer for crop production. The support of governments in East Africa to integrate insect meal in livestock feed has opened opportunities for commercializing insect products. Understanding the potential value of Black soldier fly larvae meal (BSFLM) is paramount to inform policies and practices to promote insect farming and insect-based feed for livestock production. This paper uses the economic surplus method to generate evidence on the potential socioeconomic impact of replacing conventional soybean and fish meal protein sources with insect-based feed (IBF), BSFLM, in Uganda. Results indicate that substitution of IBF for existing protein sources will generate net economic benefits of USD 0.73 billion in 20 years (0.037 billion per year). The benefit-cost ratio is estimated at 28:1, and the internal rate of return is 138%, indicating that the insect-based animal feed industry is a profitable investment. Even in the worst-case scenario, when the replacement rate of IBF and its economic benefits are reduced by half, the benefit-cost ratio remains high (8:1). The estimated economic benefit can lift about 4.53 million people above the poverty line in the country. It can also create about 1,252─563,302 new jobs per annum, depending on the substitution rate of conventional protein feeds with IBF (0.1%─45%). Uganda has the potential to produce from about 3,244 tons to 1.5 million tons of IBF. Similarly, using the same replacement rates, the country can produce about 695─312,678 tons of NPK fertilizer from biowaste recycling. About 0.09-41 million tons of biowaste could be recycled, depending on the replacement rate of conventional feed sources with IBF. Our results justify that investing in the insect feed value chain can contribute to Uganda’s economic, social, and environmental sustainability.
Feeding juvenile largemouth bass (Micropterus salmoides) with carboxymethyl cellulose with different viscous: Impacts on nutrient digestibility, growth, and hepatic and gut morphology
Authors: Liu Yu , Fan Jiongting , Zhou Hang , Zhang Yumeng , Huang Huajing , Cao Yixiong , Zhang Wei , Deng Junming , Tan Beiping
Published: November 2022

A 56-day trial investigated the impact of the dietary inclusion of cellulose with different viscosities on the growth, nutrient digestibility, serum biochemical indices, and the hepatic and gut morphology of largemouth bass juveniles. Four practical diets (42.50% protein and 13.70% lipid) were designed containing 8% microcrystalline cellulose (MC) and carboxymethyl cellulose (CMC) of 2,500, 5,000, and 6,500 mPa s dynamic viscosity [named MC, low-viscosity CMC (Lvs-CMC), medium-viscosity CMC (Mvs-CMC), and high-viscosity CMC (Hvs-CMC) groups, respectively]. Fish of a uniform size (6.0 g) were randomly assigned into 16 cages, with 40 fish per cage. The results showed that the protein and lipid deposition rates, specific growth rate, protein efficiency ratio, and the weight gain rate decreased significantly in the CMC groups compared to the MC group, whereas the feed intake and feed coefficient rate exhibited the opposite trend. Moreover, the intestinal Na+/K+-ATPase, alkaline phosphatase, and lipase activities significantly decreased in the Mvs-CMC and Hvs-CMC groups compared to the MC group, as well as the serum triglyceride, total cholesterol, and high-/low-density lipoprotein contents. The nutrient apparent digestibility significantly decreased in the CMC groups compared to the MC group. The viscerosomatic and intestinal length indices in the CMC groups and the villus height in the Hvs-CMC group were significantly lower than those in the MC group, whereas the number of gut goblet cells and muscular thickness in the Mvs-CMC and Hvs-CMC groups exhibited opposing results. The results also showed that dietary CMC damaged the hepatic and gut morphology and decreased the digestive enzyme activity, nutrient apparent digestibility, and growth of largemouth bass. In summary, viscosity is the main anti-nutritional effect of dietary CMC and soluble non-starch polysaccharides.
The design and calibration of a low-cost underwater sound velocity profiler
Authors: Zhang Shengzong , Xu Xiaoyang , Xu Dazhen , Long Keliu , Shen Chong , Tian Chuan
Published: November 2022

The sound velocity profile is the base of various underwater acoustic equipment. In this paper, a low-cost sound velocity profiler is designed based on the time difference method. It mainly includes three parts: the control unit, the storage module and the ultrasonic measurement module. Its overall volume is small, and the standby power consumption is low. It can be integrated into various underwater measurement platforms and profilers to realize the sound velocity measurement, and it also could be used as a self-contained sound velocity sensor. Furthermore, according to the sound velocity measurement principle and response characteristics, a calibration algorithm based on Recurrent Neural Network (RNN) and Discrete Wavelet Transformation (DWT) is proposed, which can improve the accuracy and adapt to the nonlinear response of the system by using multiple sets of time data obtained from the measurements. It is verified by calibration experiments that the neural network calibration algorithm can effectively reduce the nonlinear system error in the measurement, and its effect is better than the traditional linear regression method. The designed system prototype can achieve measurement accuracy of 0.05m/s after calibration, which can meet the needs of low-cost and high-precision underwater sound velocity measurement.
Investigating dysbiosis and microbial treatment strategies in inflammatory bowel disease based on two modified Koch’s postulates
Authors: Zhao HanZheng , Zhang WenHui , Cheng Die , You LiuPing , Huang YueNan , Lu YanJie
Published: November 2022

Inflammatory bowel disease (IBD) is a chronic non-specific inflammatory disease that occurs in the intestinal tract. It is mainly divided into two subtypes, i.e., the Crohn’s disease (CD) and ulcerative colitis (UC). At present, its pathogenesis has not been fully elucidated, but it has been generally believed that the environment, immune disorders, genetic susceptibility, and intestinal microbes are the main factors for the disease pathogenesis. With the development of the sequencing technology, microbial factors have received more and more attention. The gut microbiota is in a state of precise balance with the host, in which the host immune system is tolerant to immunogenic antigens produced by gut commensal microbes. In IBD patients, changes in the balance between pathogenic microorganisms and commensal microbes lead to changes in the composition and diversity of gut microbes, and the balance between microorganisms and the host would be disrupted. This new state is defined as dysbiosis. It has been confirmed, in both clinical and experimental settings, that dysbiosis plays an important role in the occurrence and development of IBD, but the causal relationship between dysbiosis and inflammation has not been elucidated. On the other hand, as a classic research method for pathogen identification, the Koch’s postulates sets the standard for verifying the role of pathogens in disease. With the further acknowledgment of the disease pathogenesis, it is realized that the traditional Koch’s postulates is not applicable to the etiology research (determination) of infectious diseases. Thus, many researchers have carried out more comprehensive and complex elaboration of Koch’s postulates to help people better understand and explain disease pathogenesis through the improved Koch’s postulates. Therefore, focusing on the new perspective of the improved Koch’s postulates is of great significance for deeply understanding the relationship between dysbiosis and IBD. This article has reviewed the studies on dysbiosis in IBD, the use of microbial agents in the treatment of IBD, and their relationship to the modified Koch’s postulates.
Shotgun metagenomic sequencing analysis of ocular surface microbiome in Singapore residents with mild dry eye
Authors: Tong Louis , Constancias Florentin , Hou Aihua , Chua Song Lin , Drautz-Moses Daniela I. , Schuster Stephan Christoph , Yang Liang , Williams Rohan B. H. , Kjelleberg Staffan
Published: November 2022

The ocular surface microbiome has implications for ocular surface inflammation and immunology. Previous shotgun metagenomics analyses were performed in China, showing results that differed according to environment and age. Patients with Sjogren’s syndrome were reported to have altered conjunctival microbiome, but such studies have not been done in milder dry eye. The aim of this study is to describe the conjunctival microbiome in people with mild dry eye in Singapore. Samples were collected from 14 participants with mild dry eye and 10 age-matched comparison participants recruited from Singapore National Eye Centre (SNEC) clinics. Shotgun metagenomic sequencing analysis was employed to evaluate the conjunctival microbiome composition. Proteobacteria formed the predominant phylum in the conjunctiva. As in a study from a coastal city in China, Achromobacter spp. was numerically most abundant. Compared to age-matched controls, the conjunctival microbial composition in mild dry eye was similar. Several microorganisms, including Streptococcus spp. increased in representation with age, and the abundance of Staphylococcus correlated with Schirmer readings. In addition, when cultured corneal epithelial cells were exposed to three strains of Achromobacter xylosoxidans, cytokines such as TNF-α and IL-6 were upregulated in the cell lysates and supernatants. Ourresults suggest that age is an important factor that affects composition of the conjunctival microbiome, and relative abundance of specific microorganism may vary according to the environment of the human host.