bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-Cov-2 spike induces intestinal barrier dysfunction through the interaction between CEACAM5 and Galectin-9
Authors: Luo Yingshu , Zhang Zhenling , Ren Jiangnan , Dou Chunxu , Wen Jiancheng , Yang Yang , Li Xiaofeng , Yan Zhixiang , Han Yanzhi
Published: April 2024

Background

Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), as a typical tumor marker, has been found to exert immunomodulatory effects in many diseases. We previously reported the clinical and molecular evidences supporting that SARS-Cov-2 infected the gastrointestinal (GI) tract and found a reduction of CEACAM5 in COVID-19 patients’ feces which associated with gut dysbiosis. Yet the role of CEACAM5 in GI infection is ill-defined.

Methods

Mice models were established through intraperitoneally injecting with recombinant viral spike-Fc to mimic the intestinal inflammation. We collected duodenum, jejunum, ileum and colon samples after 6h, 2 days, 4 days and 7 days of spike-Fc or control-Fc injection to perform proteomic analysis. Blood was collected from healthy donors and peripheral blood mononuclear cells (PBMC) were separated by density gradient centrifugation, then CD4+ T cells were isolated with magnetic beads and co-cultured with Caco-2 cells.

Results

In addition to intestinal CEACAM5, the expression of tight junction and the percent of CD4+ T lymphocytes were significantly decreased in spike-Fc group compared to control (p < 0.05), accompanied with increased level of inflammatory factors. The KEGG analysis revealed differentially expressed proteins were mainly enriched in the coronavirus disease (COVID-19), tight junction, focal adhesion, adherens junction and PI3K-Akt signaling pathway. Protein–protein interaction (PPI) network analysis identified the interaction between CEACAM5 and Galectin-9 that was also verified by molecular docking and co-IP assay. We further confirmed a reduction of CEACAM5 in SARS-CoV-2 spike stimulated enterocytes could promote the expression of Galectin-9 protein in CD4+T cells. Then it gave rise to the increasing release of inflammatory factors and increased apoptosis of CD4+T cells by inhibition of PI3K/AKT/mTOR pathway. Ultimately intestinal barrier dysfunction happened.

Conclusion

Our results indicated that CEACAM5 overexpression and Galectin-9 knockdown played a protective role in intestinal barrier injury upon spike-Fc stimulation. Collectively, our findings identified firstly that SARS-CoV-2 spike induced intestinal barrier dysfunction through the interaction between CEACAM5 and Galectin-9. The result provides potential therapeutic targets in intestinal barrier dysfunction for treating severe COVID patients.
Hesperidin - loaded PVA/alginate hydrogel: targeting NFκB/iNOS/COX-2/TNF-α inflammatory signaling pathway
Authors: Kodous Ahmad S. , Abdel-Maksoud Mostafa A. , El-Tayeb Mohamed A. , Al-Sherif Diana A. , Mohamed Suzan Shawky Abuelkasem , Ghobashy Mohamed Mohamady , Emad Ayat M. , Abd El‐Halim Shady M. , Hagras Soheir A. A. , Mani Samson , Rao Arunagiri Kuha Deva Magendhra , Hussein Ahmed M. , Saada Helen N.
Published: April 2024

Introduction

Skin injuries represent a prevalent form of physical trauma, necessitating effective therapeutic strategies to expedite the wound healing process. Hesperidin, a bioflavonoid naturally occurring in citrus fruits, exhibits a range of pharmacological attributes, including antimicrobial, antioxidant, anti-inflammatory, anticoagulant, and analgesic properties. The main objective of the study was to formulate a hydrogel with the intention of addressing skin conditions, particularly wound healing.

Methods

This research introduces a methodology for the fabrication of a membrane composed of a Polyvinyl alcohol - Sodium Alginate (PVA/A) blend, along with the inclusion of an anti-inflammatory agent, Hesperidin (H), which exhibits promising wound healing capabilities. A uniform layer of a homogeneous solution comprising PVA/A was cast. The process of crosslinking and the enhancement of hydrogel characteristics were achieved through the application of gamma irradiation at a dosage of 30 kGy. The membrane was immersed in a Hesperidin (H) solution, facilitating the permeation and absorption of the drug. The resultant system is designed to deliver H in a controlled and sustained manner, which is crucial for promoting efficient wound healing. The obtained PVA/AH hydrogel was evaluated for cytotoxicity, antioxidant and free radical scavenging activities, anti-inflammatory and membrane stability effect. In addition, its action on oxidative stress, and inflammatory markers was evaluated on BJ-1 human normal skin cell line.

Results and Discussion

We determined the effect of radical scavenging activity PVA/A (49 %) and PVA/AH (87%), the inhibition of Human red blood cell membrane hemolysis by PVA/AH (81.97 and 84.34 %), hypotonicity (83.68 and 76.48 %) and protein denaturation (83.17 and 85.8 %) as compared to 250 μg/ml diclofenac (Dic.) and aspirin (Asp.), respectively. Furthermore, gene expression analysis revealed an increased expression of genes associated with anti-oxidant and anti-inflammatory properties and downregulated TNFα, NFκB, iNOS, and COX2 by 67, 52, 58 and 60%, respectively, by PVA/AH hydrogel compared to LPS-stimulated BJ-1 cells. The advantages associated with Hesperidin can be ascribed to its antioxidant and anti-inflammatory attributes. The incorporation of Hesperidin into hydrogels offers promise for the development of a novel, secure, and efficient strategy for wound healing. This innovative approach holds potential as a solution for wound healing, capitalizing on the collaborative qualities of PVA/AH and gamma irradiation, which can be combined to establish a drug delivery platform for Hesperidin.
Identification of potential biomarkers of gout through weighted gene correlation network analysis
Authors: Wang Xinyi , Yang Bing , Xiong Tian , Qiu Yu , Qin Yingfen , Liang Xinghuan , Lu Decheng , Yang Xi
Published: April 2024

Background

Although hyperuricemia is not always associated with acute gouty arthritis, uric acid is a significant risk factor for gout. Therefore, we investigated the specific mechanism of uric acid activity.

Methods

Using the gout-associated transcriptome dataset GSE160170, we conducted differential expression analysis to identify differentially expressed genes (DEGs). Moreover, we discovered highly linked gene modules using weighted gene coexpression network analysis (WGCNA) and evaluated their intersection. Subsequently, we screened for relevant biomarkers using the cytoHubba and Mcode algorithms in the STRING database, investigated their connection to immune cells and constructed a competitive endogenous RNA (ceRNA) network to identify upstream miRNAs and lncRNAs. We also collected PBMCs from acute gouty arthritis patients and healthy individuals and constructed a THP-1 cell gout inflammatory model, RT−qPCR and western blotting (WB) were used to detect the expression of C-X-C motif ligand 8 (CXCL8), C-X-C motif ligand 2 (CXCL2), and C-X-C motif ligand 1 (CXCL1). Finally, we predicted relevant drug targets through hub genes, hoping to find better treatments.

Results

According to differential expression analysis, there were 76 upregulated and 28 downregulated mRNAs in GSE160170. Additionally, WGCNA showed that the turquoise module was most strongly correlated with primary gout; 86 hub genes were eventually obtained upon intersection. IL1β, IL6, CXCL8, CXCL1, and CXCL2 are the principal hub genes of the protein–protein interaction (PPI) network. Using RT−qPCR and WB, we found that there were significant differences in the expression levels of CXCL8, CXCL1, and CXCL2 between the gouty group and the healthy group, and we also predicted 10 chemicals related to these proteins.

Conclusion

In this study, we screened and validated essential genes using a variety of bioinformatics tools to generate novel ideas for the diagnosis and treatment of gout.
Sulfasalazine-induced drug reaction with eosinophilia and systemic symptoms (DRESS) coinfected with COVID-19 complicated by hemophagocytic lymphohistiocytosis: a case report
Authors: Li Mengmeng , li Furong , Dai Yang , Zeng Yunou Zhang , Chen Xiaomei
Published: April 2024

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is characterized by a widespread maculopapular rash, lymphadenopathy, fever, and multisystem involvement. Conversely, hemophagocytic lymphohistiocytosis (HLH) is an infrequent yet critical condition presenting with fever, hepatosplenomegaly, cytopenias, coagulation abnormalities, and elevated inflammatory markers. The overlapping clinical and laboratory features between DRESS and HLH poses a significant diagnostic challenge. Secondary HLH (sHLH) typically occurs in adults triggered by viral infections, malignancies, rheumatologic diseases, or immune deficiencies. Recently, COVID-19 has also been identified as one of the triggers for sHLH. Herein, we present a case of Sulfasalazine-induced DRESS coinfected with COVID-19 that subsequently progressed into HLH. Our patient exhibited common hepatorenal and splenic involvement along with rare cholecystitis and appendicitis. However, a significant improvement was observed upon the addition of etoposide and azathioprine. We hypothesize that excessive activation of the immune system and cytokine storm due to DRESS combined with COVID-19 infection led to more extensive systemic damage resulting in HLH development. This highlights the potential for severe consequences when DRESS coincides with HLH during a COVID-19 infection.
First stable isotope and mercury assessment of bonnethead and Caribbean sharpnose sharks from a potential nursery ground in the Archipelago of Bocas del Toro, Panamanian Caribbean
Authors: Barragán-Barrera Dalia C. , Polo-Silva Carlos J. , González Cindy , Rodríguez Miguel , Baldrich Laura , Bermúdez-Rivas Christian , Moncaleano-Niño Ángela Margarita , Bustamante Paco , Caballero Susana , Luna-Acosta Andrea
Published: April 2024

Bonnethead and Caribbean sharpnose sharks frequent coastal waters, rendering them vulnerable to overexploitation, with the bonnethead shark listed as endangered by the IUCN. Marine Protected Areas (MPAs) have been suggested as a management strategy to regulate shark-exploitation. Moreover, it’s essential to identify key areas where nursery grounds (NG) and adult habitats overlap to prioritize conservation zones within MPAs. Along the Caribbean Sea, several NG have been identified for larger shark species, but little is known for smaller sharks. In Bocas del Toro (BDT-Panamanian Caribbean), both bonnethead and Caribbean sharpnose sharks are distributed, with the former appearing to be genetically isolated. The local MPA in BDT doesn't include a NG identified near Solarte Island. In this study, to provide ecological information on bonnethead and Caribbean sharpnose sharks within this potential NG, we evaluated stable isotopes (δ13C and δ15N) and total-mercury (THg) values in their fins. The results revealed a higher proportion of small-adult sharks in the NG, emphasizing the necessity of conducting a comprehensive study to further characterize this area. Moreover, there was no niche-partitioning between the two species and their diets primarily consisted of small prey-items, as evidenced by the significant and negative relationship between isotopic values. Both species exhibited low THg levels in their fins. Based on these initial results and previous genetic data, it appears that BDT plays a critical role as a habitat for sharks. Thus, extending the local MPA to cover the potential NG could effectively ensure conservation of bonnethead and Caribbean sharpnose sharks in BDT.
Effect of the prism and Maddox rod test as the surgical target for type III acute acquired comitant esotropia
Authors: Wang Huihang , Zheng Weidong
Published: April 2024

Introduction

This study aims to explore more accurate and efficient examination methods to provide precise target surgical measurements for patients with type III acute acquired comitant esotropia (AACE).

Methods

The study conducted a retrospective analysis of 108 patients diagnosed with AACE who received surgical treatment at the Department of Ophthalmology, the First Affiliated Hospital of Fujian Medical University, from January 2018 to September 2023. All patients underwent examinations of the deviation angle, including the Hirschberg test, prism and Maddox rod test (PMT), and prism and alternate cover test (PACT). For the PACT, the minimum value (PACTmin) and maximum value (PACTmax) were obtained based on differences in examination methods, as well as the deviation angle range (PACT range), which represents the difference between PACTmax and PACTmin. Postoperatively, these patients were followed up for at least 6 months to assess changes in eye position and whether diplopia symptoms recurred.

Results

In both near and distant examinations, the results of PACTmax were significantly greater than those of PACTmin (p < 0.001), while the deviation angles obtained from PACTmax and PMT showed no significant statistical difference [p = 0.689 (33 cm), p = 0.436 (5 m)]. There was a strong linear correlation between PACTmin and PMT at both near (R = 0.8887) and distant (R = 0.8950) distances, but each PACTmin corresponded to multiple PMT values. There was no significant difference between the results of PACT range at near and distant distances (p = 0.531). The deviation angles obtained by PMT and PACTmin significantly decreased postoperatively compared to preoperative values, and diplopia disappeared in all patients, with alternative cover test showing no movement or presenting as an esophoria state.

Conclusion

The PMT can provide precise target surgical measurements for type III AACE, making it a fast, effective, and cost-efficient examination method. It is worthy of being promoted and applied in clinical practice.
Perspectives on systematic capacity building in pharmaceutical regulation for regulators of medical products
Authors: Gwaza Luther , Chemwolo Andrew , Musonda Mario , Kuwana Rutendo , Dube Admire
Published: April 2024

Having a robust, integrated regulatory system is important for ensuring the availability of safe and efficacious medical products of good quality and for protecting public health. However, less than 30% of countries globally have reached the required regulatory maturity level three, with low- and middle-income countries facing challenges in attracting and retaining qualified staff. World Health Organization (WHO) advocates for systematic workforce development, including competency-based education, to address these gaps. We provide perspectives on a systematic approach to capacity building of medicine regulators based on the experience and lessons learnt in developing and piloting the WHO global competency framework for medicine regulators through three scenarios. A systematic approach to capacity building, such as the human performance technology model, can be used to implement the WHO competency framework as part of organizational performance improvement while ensuring that initiatives are well-defined, targeted, and aligned with organizational goals. The competency framework can be used in different contexts, such as improving organization performance for individual regulatory authorities, strengthening regional collaborations, harmonization and reliance on medical products assessment and joint good manufacturing practices inspections of pharmaceutical manufacturers, and developing learning programs for medicine regulators. A competency-based learning approach for regulatory professionals ensures the transfer of learning to the workplace by integrating real-world practices in learning activities and assessments. Further work is required to develop and validate the assessment instruments, apply the competency framework in other contexts, expanding the learning programmes while continuously providing feedback for further refinement of the competency framework and implementation support tools.
New insights into the relationship between the average nucleotide identity and the digital DNA–DNA hybridization values in the genus Amycolatopsis and Amycolatopsis cynarae sp. nov., a novel actinobacterium from the rhizosphere soil of Cynara scolymus, and proposal of Amycolatopsis niigatensis as a synonym of Amycolatopsis echigonensis based on comparative genomic analysis
Authors: Deng Aihua , Fu Li , Mo Ping , Zheng Yaxi , Tang Ting , Gao Jian
Published: April 2024

At present, it is widely believed that a 95–96% average nucleotide identity (ANI) value is equivalent to a 70% digital DNA–DNA hybridization (dDDH) value in the prokaryotic taxonomy. However, in the present study, comparative genome analysis of 29 pairs of Amycolatopsis type strains revealed that a 70% dDDH value did not correspond to a 95–96% ANI based on the MuMmer ultra-rapid aligning tool (ANIm) but approximately corresponded to a 96.6% ANIm value in the genus Amycolatopsis. Based on this corresponding relationship, phenotypic and chemotaxonomical characteristics, as well as phylogenetic analysis, an actinobacterial strain HUAS 11-8T isolated from the rhizosphere soil of Cynara scolymus, was subjected to a polyphasic taxonomic characterization. Based on EzBioCloud alignment, it was found that strain HUAS11-8T had the 16S rRNA gene similarities of 99.78% with A. rhizosphaerae JCM 32589T, 97.8% with A. dongchuanensis YIM 75904T, and < 97.8% sequence similarities to other Amycolatopsis species. Phylogenetic analysis of 16S rRNA gene sequences and whole-genome sequences revealed that strain HUAS 11-8T was closely related to A. rhizosphaerae JCM 32589T. ANIm and dDDH values between strains HUAS 11-8T and A. rhizosphaerae JCM 32589T were 96.3 and 68.5%, respectively, lower than the 96.6 and 70% thresholds recommended for the delineation of a novel Amycolatopsis species. Consequently, strain HUAS 11-8T should represent a novel Amycolatopsis species, for which the name Amycolatopsis cynarae sp. nov. (type strain HUAS 11-8T = MCCC 1K08337T = JCM 35980T) is proposed. Furthermore, based on comparative genomic analysis and rule 42 of the Prokaryotic Code, we propose that Amycolatopsis niigatensis is a later heterotypic synonym of Amycolatopsis echigonensis.
Microbial signatures in human periodontal disease: a metatranscriptome meta-analysis
Authors: Ovsepian Armen , Kardaras Filippos S. , Skoulakis Anargyros , Hatzigeorgiou Artemis G.
Published: April 2024

The characterization of oral microbial communities and their functional potential has been shaped by metagenomics and metatranscriptomics studies. Here, a meta-analysis of four geographically and technically diverse oral shotgun metatranscriptomics studies of human periodontitis was performed. In total, 54 subgingival plaque samples, 27 healthy and 27 periodontitis, were analyzed. The core microbiota of the healthy and periodontitis group encompassed 40 and 80 species, respectively, with 38 species being common to both microbiota. The differential abundance analysis identified 23 genera and 26 species, that were more abundant in periodontitis. Our results not only validated previously reported genera and species associated with periodontitis with heightened statistical significance, but also elucidated additional genera and species that were overlooked in the individual studies. Functional analysis revealed a significant up-regulation in the transcription of 50 gene families (UniRef-90) associated with transmembrane transport and secretion, amino acid metabolism, surface protein and flagella synthesis, energy metabolism, and DNA supercoiling in periodontitis samples. Notably, the overwhelming majority of the identified gene families did not exhibit differential abundance when examined across individual datasets. Additionally, 4 bacterial virulence factor genes, including TonB dependent receptor from P. gingivalis, surface antigen BspA from T. forsynthia, and adhesin A (PsaA) and Type I glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the Streptococcus genus, were also found to be significantly more transcribed in periodontitis group. Microbial co-occurrence analysis demonstrated that the periodontitis microbial network was less dense compared to the healthy network, but it contained more positive correlations between the species. Furthermore, there were discernible disparities in the patterns of interconnections between the species in the two networks, denoting the rewiring of the whole microbial network during the transition to the disease state. In summary, our meta-analysis has provided robust insights into the oral active microbiome and transcriptome in both health and disease.
Development of a dual immunochromatographic test strip to detect E2 and Erns antibodies against classical swine fever
Authors: Huynh Loc Tan , Sohn Eun-Ju , Park Youngmin , Kim Juhun , Shimoda Tomohiko , Hiono Takahiro , Isoda Norikazu , Hong Sung-Hee , Lee Ha-Na , Sakoda Yoshihiro
Published: April 2024

Background

It is essential to consider a practical antibody test to successfully implement marker vaccines and validate vaccination efficacy against classical swine fever virus (CSFV). The test should include a serological antibody assay, combined with a tool for differentiating infected from vaccinated animals (DIVA). The immunochromatographic test strip (ICS) has been exclusively designed for detecting CSFV E2 antibodies while lacking in detecting Erns antibodies, which can be employed and satisfy DIVA strategy. This study developed a novel ICS for detecting CSFV E2/Erns dual-antibody. The effectiveness of ICS in evaluating the DIVA capability of two novel chimeric pestivirus vaccine candidates was assessed.

Methods

Recombinant E2 or Erns protein was transiently expressed in the plant benthamiana using Agrobacterium tumefaciens. ICS was subsequently assembled, and goat anti-rabbit IgG and recombinant CSFV E2 or Erns protein were plated onto the nitrocellulose membrane as control and test lines, respectively. The sensitivity and specificity of ICS were evaluated using sera with different neutralizing antibody titers or positive for antibodies against CSFV and other pestiviruses. The coincidence rates for detecting E2 and Erns antibodies between ICS and commercial enzyme-linked immunosorbent assay (ELISA) kits were also computed. ICS performance for DIVA capability was evaluated using sera from pigs vaccinated with conventional vaccine or chimeric vaccine candidates.

Results

E2 and Erns proteins were successfully expressed in N. benthamiana-produced recombinant proteins. ICS demonstrated high sensitivity in identifying CSFV E2 and Erns antibodies, even at the low neutralizing antibody titers. No cross-reactivity with antibodies from other pestiviruses was confirmed using ICS. There were high agreement rates of 93.0 and 96.5% between ICS and two commercial ELISA kits for E2 antibody testing. ICS also achieved strong coincidence rates of 92.9 and 89.3% with two ELISA kits for Erns antibody detection. ICS confirmed the absence of CSFV Erns-specific antibodies in sera from pigs vaccinated with chimeric vaccine candidates.

Conclusion

E2 and Erns proteins derived from the plant showed great potential and can be used to engineer a CSFV E2/Erns dual-antibody ICS. The ICS was also highly sensitive and specific for detecting CSFV E2 and Erns antibodies. Significantly, ICS can fulfill the DIVA concept by incorporating chimeric vaccine candidates.
Efficacy and mechanism of acupuncture for functional constipation in older adults: study protocol for a randomized controlled trial
Authors: Huai Yisheng , Fan Qian , Dong Yiyue , Li Xu , Hu Junwei , Liu Lumin , Chen Yuelai , Yin Ping
Published: April 2024

Introduction

Functional constipation (FC) is a common functional gastrointestinal disorder in clinical practice, with the prevalence of which increasing with age. With the increasing aging of the population worldwide, this problem is bound to become more prominent. Acupuncture is effective and recommended for the treatment of FC. However, little is known about how acupuncture affects the gut microbiota and inflammatory cytokines and thus improves gut function. Meanwhile, there are few high-quality clinical trials specifically focusing on acupuncture in treating FC in older people. The objective of this study is to assess the efficacy and safety of acupuncture in treating FC in older people. Additionally, the research aims to explore the mechanism of action of acupuncture in treating FC in older people by affecting intestinal microbiota and inflammation cytokines.

Methods and analysis

This study is designed as a single-center, randomized, sham-controlled clinical trial. A total of 98 eligible FC patients will be randomized in a 1:1 ratio into an acupuncture group and a sham acupuncture group. Both groups will receive 24 treatments over 8 weeks with a 12-week follow-up. The primary outcome of the study is the treatment response rate, which is the proportion of participants with ≥3 mean weekly Complete Spontaneous Bowel Movements (CSBMs) over weeks 3–8. The secondary outcomes will include the proportion of participants with ≥3 mean weekly CSBMs during other assessment periods; the percentage of patients with ≥1 increase in mean weekly CSBMs from baseline; the average changes in CSBMs; Patient Assessment of Constipation-Symptoms (PAC-SYM), Bristol Stool Scale, Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) and weekly usage of emergency bowel medications. Adverse events will be recorded throughout the study. Data for the outcomes will be collected at Week 0 (baseline), Week 4 (the intervention period), Week 8 (the post-treatment), Week 12 (the follow-up period) and Week 20 (the follow-up period). In addition, changes in intestinal microbiota will be analyzed using 16S rRNA high-throughput detection, and the concentration of relevant inflammatory cytokines in serum will be measured by ELISA based on blood samples. The intention-to-treat analysis will be performed in this study.

Clinical trial registration: [https://www.chictr.org.cn/], identifier [ChiCTR2300070735].
A review of the applications of generative adversarial networks to structural and functional MRI based diagnostic classification of brain disorders
Authors: Huynh Nguyen , Deshpande Gopikrishna
Published: April 2024

Structural and functional MRI (magnetic resonance imaging) based diagnostic classification using machine learning has long held promise, but there are many roadblocks to achieving their potential. While traditional machine learning models suffered from their inability to capture the complex non-linear mapping, deep learning models tend to overfit the model. This is because there is data scarcity and imbalanced classes in neuroimaging; it is expensive to acquire data from human subjects and even more so in clinical populations. Due to their ability to augment data by learning underlying distributions, generative adversarial networks (GAN) provide a potential solution to this problem. Here, we provide a methodological primer on GANs and review the applications of GANs to classification of mental health disorders from neuroimaging data such as functional MRI and showcase the progress made thus far. We also highlight gaps in methodology as well as interpretability that are yet to be addressed. This provides directions about how the field can move forward. We suggest that since there are a range of methodological choices available to users, it is critical for users to interact with method developers so that the latter can tailor their development according to the users' needs. The field can be enriched by such synthesis between method developers and users in neuroimaging.
Piquin chili, a wild spice: natural variation in nutraceutical contents
Authors: Pérez-Ramírez Rogelio , Moreno-Ramírez Yolanda del Rocio , Ruiz-De-La-Cruz Gilberto , Juárez-Aragón María Cruz , Aguirre-Mancilla César Leobardo , Niño-García Nohemí , Torres-Castillo Jorge Ariel
Published: April 2024

The piquin chili is a wild spice widely consumed from the South United States to Central America and stands out as a source of flavonoids, essential metabolites with antioxidant properties. The concentrations of flavonoids, carotenoids, and capsaicinoids vary according to regions, maturity stages, and ripening processes. These compounds, which are known for their health benefits and industrial applications, highlight the importance of identifying ideal environmental conditions for collecting fruits with the highest contents. Comprehensive studies of the piquin chili are essential for understanding its properties for the benefit of consumers. This approach fortifies trade, contributes to resource conservation, and advances cultivated chili production.
Antibody–drug conjugates in urothelial carcinoma: scientometric analysis and clinical trials analysis
Authors: Zhang Meng , Zuo Yuanye , Chen Siyi , Li Yaonan , Xing Yang , Yang Lei , Wang Hong , Guo Rui
Published: April 2024

In 2020, bladder cancer, which commonly presents as urothelial carcinoma, became the 10th most common malignancy. For patients with metastatic urothelial carcinoma, the standard first-line treatment remains platinum-based chemotherapy, with immunotherapy serving as an alternative in cases of programmed death ligand 1 expression. However, treatment options become limited upon resistance to platinum and programmed death 1 or programmed death ligand 1 agents. Since the FDA’s approval of Enfortumab Vedotin and Sacituzumab Govitecan, the therapeutic landscape has expanded, heralding a shift towards antibody–drug conjugates as potential first-line therapies. Our review employed a robust scientometric approach to assess 475 publications on antibody–drug conjugates in urothelial carcinoma, revealing a surge in related studies since 2018, predominantly led by U.S. institutions. Moreover, 89 clinical trials were examined, with 36 in Phase II and 13 in Phase III, exploring antibody–drug conjugates as both monotherapies and in combination with other agents. Promisingly, novel targets like HER-2 and EpCAM exhibit substantial therapeutic potential. These findings affirm the increasing significance of antibody–drug conjugates in urothelial carcinoma treatment, transitioning them from posterior-line to frontline therapies. Future research is poised to focus on new therapeutic targets, combination therapy optimization, treatment personalization, exploration of double antibody-coupled drugs, and strategies to overcome drug resistance.
Evaluating first-line therapeutic strategies for metastatic castration-resistant prostate cancer: a comprehensive network meta-analysis and systematic review
Authors: Zhang Duojie , Weng Haimin , Zhu Zhangji , Gong Weilun , Ma Yinfeng
Published: April 2024

Objective

This study aimed to evaluate the relative efficacy and safety of first-line treatment options for metastatic castration-resistant prostate cancer (mCRPC).

Methods

We systematically searched electronic databases, including PubMed and Web of Science, for studies published from their inception to April 3rd, 2023. Inclusion criteria were: 1) Completed Phase III or IV randomized controlled trials (RCTs) registered on ClinicalTrials.gov; 2) Patients with a confirmed diagnosis of mCRPC who had not previously received chemotherapy or novel endocrine therapies. We conducted a network meta-analysis using R software (version 3.4.0). Network graphs and risk of bias graphs were generated using Stata 14.0 and RevMan 5.4, respectively. The primary outcome was overall survival (OS), and the secondary outcome was the incidence of severe adverse events (SAEs).

Results

Seven RCTs encompassing 6,641 patients were included. The network meta-analysis revealed that both docetaxel+prednisone (DP) and cabazitaxel+prednisone (CP) significantly improved OS compared to abiraterone. Compared to placebo, DP showed comparable results to both cabazitaxel 20 mg/m^2+prednisone (C20P) and cabazitaxel 25 mg/m^2+prednisone (C25P) in terms of OS. For SAEs, both DP and C20P were superior to C25P, with no statistical difference between C20P and DP. The probability ranking plots indicated that C25P ranked highest for OS, while DP ranked highest for SAEs.

Conclusions

Based on our network meta-analysis, we recommend cabazitaxel 20 mg/m^2+prednisone (C20P) as the primary choice for first-line management of mCRPC, followed by DP. Enzalutamide and abiraterone are suggested as subsequent options. Radium-223 may be considered for patients presenting with bone metastases.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42023443943.
Case report: A germline CHEK1 c.613 + 2T>C leads to a splicing error in a family with multiple cancer patients
Authors: Qian Jun , Peng Min , Li Yanan , Liu Wei , Zou Xinwei , Chen Huafei , Zhou Sujuan , Xiao Sheng , Zhou Jinhua
Published: April 2024

Background

Genome instability plays a crucial role in promoting tumor development. Germline mutations in genes responsible for DNA repair are often associated with familial cancer syndromes. A noticeable exception is the CHEK1 gene. Despite its well-established role in homologous recombination, germline mutations in CHEK1 are rarely reported.

Case presentation

In this report, we present a patient diagnosed with ovarian clear cell carcinoma who has a family history of cancer. Her relatives include a grandfather with esophageal cancer, a father with gastric cancer, and an uncle with a brain tumor. The patient carried a typical genomic profile of clear cell carcinoma including mutations in KRAS, PPP2R1A, and PIK3R1. Importantly, her paired peripheral blood cells harbored a germline CHEK1 mutation, CHEK1 exon 6 c.613 + 2T>C, which was also found in her father. Unfortunately, the CHEK1 status of her grandfather and uncle remains unknown due to the unavailability of their specimens. Further evaluation via RT-PCR confirmed a splicing error in the CHEK1 gene, resulting in truncation at the kinase domain region, indicative of a loss-of-function mutation.

Conclusion

This case highlights a rare germline CHEK1 mutation within a family with a history of cancer. The confirmed splicing error at the mRNA level underscores the functional consequences of this mutation. Documenting such cases is vital for future evaluation of inheritance patterns, clinical penetrance of the mutation, and its association with specific cancer types.
The effects of foliar amino acid and Zn applications on agronomic traits and Zn biofortification in soybean (Glycine max L.)
Authors: Han Şule , Sönmez İlker , Qureshi Moin , Güden Birgül , Gangurde Sunil S. , Yol Engin
Published: April 2024

The production and consumption of soybeans are widespread due to their nutritional and industrial value. Nutrient enrichment is vital for improving the nutritional quality of soybeans. This study aimed to evaluate the effect of foliar application of amino acids (AA) and zinc (Zn) on agronomic traits and the accumulation of grain Zn in soybeans. The experimental design comprised 16 treatment combinations involving four levels of amino acid application (0, 50, 100, and 150 ml 100 L-1) and Zn (0, 2, 4, and 6 mg L-1) following a randomized complete block design with three replications in field conditions. The results demonstrated that the application of foliar Zn and AA did not affect the yield, whereas that of AA50*Zn2 and AA150*Zn2 affected the number of pods and branches. The effects of AA application on N and the protein content in grains were determined to be significant. The application of AA100*Zn6 emerged as the most effective treatment for the enhancement of Zn biofortification in soybean grains. The combined foliar application of AA and Zn contributed to enhanced Zn accumulation in the grains.
Assessing age discrimination in workplaces: psychometric exploration of the Workplace Age Discrimination Scale (WADS-G)
Authors: Funk Maria , Lorenz Timo
Published: April 2024

In contemporary workplaces characterized by diverse age groups working collaboratively, the assessment of age discrimination as an interpersonal phenomenon has gained heightened significance. This study focuses on adapting and scrutinizing the psychometric properties of the German iteration of the Workplace Age Discrimination Scale (WADS-G). Comprehensive Confirmatory Factor Analysis (CFA) results affirm a robust fit for the unidimensional model. Convergent validity is established through correlations between WADS-G scores and related instruments, while discriminant validity is evidenced by its lack of association with extraversion. Noteworthy findings include a positive correlation with turnover intention and negative correlations with job satisfaction, occupational self-efficacy, and organizational affective commitment. Despite its merits, the predictive efficacy of the WADS-G is notably inferior when juxtaposed with the Workplace Incivility Scale. Its explanatory power for turnover intention is constrained when accounting for variables such as job satisfaction, work environment, neuroticism, and core self-evaluation. Although measurement invariance testing across gender groups reveals scalar to strict measurement invariance, the examination across age groups indicates metric invariance. However, Confirmatory Factor Analyses for the 18–30 and 50+ age groups, central to the research emphasis, reveal suboptimal model fit. These outcomes prompt a nuanced discussion on whether the WADS-G aptly captures age-discriminatory experiences across diverse age and gender cohorts among employees.
Not all mindfulness is equal: certain facets of mindfulness have important implications for well-being and mental health across the lifespan
Authors: Johnson Nathaniel J. , Smith Ryan J. , Kil Hali
Published: April 2024

The connections between the five facets of mindfulness, well-being, and mental health across the lifespan have traditionally been investigated using variable-centered approaches. Less research has investigated these relationships from a person-centered, profile-based approach. In this work, we aimed to identify the profiles of mindfulness in a Canadian lifespan sample (14 to 90 years of age) and investigate how these profiles compared on age, well-being, and mental health. An age- and gender-balanced sample of 1,600 participants completed a questionnaire that measured the five facets of mindfulness; life satisfaction; existential well-being; and anxiety, depression, and stress symptoms. A latent profile analysis was conducted. Five profiles based on the five-facet model of mindfulness were identified: high mindfulness, moderate mindfulness, low mindfulness, nonjudgmentally aware, and judgmentally observing. The 3-step approach to profile comparisons was used to assess age, mental health, and well-being differences across the profiles. Those in the high mindfulness and nonjudgmentally aware profiles were generally older, while the judgmentally observing profile contained younger individuals. Those in the high mindfulness and nonjudgmentally aware profiles reported the greatest mental health and well-being. Conversely, those in the low mindfulness and judgmentally observing profiles had worse mental health than the other profiles. The moderate mindfulness profile was situated between these profile groups on age, mental health, and well-being outcomes. This pattern of results has implications for mindfulness-based intervention research and practice to better account for heterogeneity in mindfulness and better support well-being across the lifespan.
Gratitude as an antidote to materialism in young consumers
Authors: Battistella-Lima Suzana Valente , Veludo-de-Oliveira Tânia Modesto
Published: April 2024

Introduction

Materialism has consistently been associated with mental health problems, such as depression and anxiety, and with a decline in overall wellbeing. This article seeks to deepen the understanding of whether or not the level of materialism is reduced when a sense of gratitude is instilled and, if so, how.

Methods

After a thorough literature review, two empirical studies are presented. Study 1 has a quasi-experimental design and a sample of adolescent individuals in a major city in Brazil. Study 2 takes the form of a survey, completed by parents, in the same city.

Results

Study 1 demonstrates that a gratitude-based intervention can reduce the subjects’ belief that material wealth brings happiness and signifies success. Study 2 suggests that parents who express gratitude have a perception of raising less materialistic children.

Discussion

These conclusions add to the theory and practice of consumer psychology and responsible consumption, particularly in relation to the behavior of young people, pointing toward ways to reduce excessive consumption through a simple and easily applied intervention: the stimulus of gratitude.
The moderating role of stigma in the relationship between depression and resilience: results of a cross-sectional study in university students
Authors: Rometsch Caroline , Mansueto Giovanni , Ceccatelli Sara , Cosci Fiammetta
Published: April 2024

Background/objective

Depression is a growing concern in university students and resilience has shown to play a protective role. The impact of stigma is still under-explored, with reference to its moderating role between depression and resilience. The present study investigate such a relationship among Italian university students.

Methods

A cross-sectional design was applied in a simple of 1,912 students to examine the interrelationships between depression (Patient Health Questionnaire-9), resilience (Nicholson McBride Resilience questionnaire), and stigma (Stigma-9). Correlation, predictor, and moderation analyses were applied in RStudio.

Results

A negative correlation was found between depressive symptoms and resilience (r = −0.455, p < 0.001). A positive correlation was found between depressive symptoms and stigma (r = 0.207, p < 0.001). Lower levels of resilience and higher levels of stigma were significant predictors of depressive symptoms [F(df, n) = 190.8(3, 1884), p < 0.001, R2 = 0.236]. The moderation analysis showed a weakening of resilience protective effect against depression as stigma levels increase [F(df,n) = 186.7(3,1908), p < 0.001, R2 = 0.226].

Conclusion

Stigma influences the relationship between depression and resilience. Anti-stigma interventions and programs empowering resilience, should be implemented in university settings to protect students from depression.
Comparison of changes in stress coping strategies between cognitive behavioral therapy and pharmacotherapy
Authors: Ihara Sakae , Katayama Nariko , Nogami Waka , Amano Mizuki , Noda Sachiko , Kurata Chika , Kobayashi Yuki , Sasaki Yohei , Mitsuda Dai , Ozawa Mire , Matsuoka Jun , Takemura Ryo , Uchida Hiroyuki , Nakagawa Atsuo
Published: April 2024

Background

Coping refers to conscious responses to negative circumstances, with the intention of ameliorating these situations. Few studies have compared the differences between psychotherapy and medication treatment for coping strategies for depression. In this study, we investigated the differences in coping strategies between cognitive behavioral therapy (CBT) combined with medication (CBT group) and medication alone (pharmacotherapy group) among outpatients with depression.

Methods

A prospective observational study was conducted among 50 patients with major depression (24 and 26 in the CBT and pharmacotherapy groups, respectively). Stress coping strategies (Coping Inventory for Stressful Situations [CISS]) and depression severity (Beck Depression Inventory-Second Edition [BDI-II]) were assessed at baseline and 16 weeks later. Changes in the CISS and BDI-II scores in both groups were tested using repeated analysis of variance. Inverse probability weighting with propensity score analysis was applied to address potential selection bias.

Results

At 16 weeks, the CBT group exhibited increased CISS task-oriented coping, distraction, and social diversion scores, which differed from those of the pharmacotherapy group. The CBT group exhibited a significantly greater reduction in depressive symptoms than the pharmacotherapy group.

Limitations

This study was not a randomized controlled trial and thus may have selection bias.

Conclusion

Gaining adaptive coping skills, including task-oriented coping, distraction, and social diversion skills, by combining CBT with medication may lead to greater improvement in depression symptoms. These findings suggest that clinicians should evaluate coping strategies and facilitate the acquisition of adaptive coping strategies in patients with depression to reduce their symptoms.
Zmiz1 is a novel regulator of brain development associated with autism and intellectual disability
Authors: K. C. Rajan , Tiemroth Alina S. , Thurmon Abbigail N. , Meadows Stryder M. , Galazo Maria J.
Published: April 2024

Neurodevelopmental disorders (NDDs) are a class of pathologies arising from perturbations in brain circuit formation and maturation with complex etiological triggers often classified as environmental and genetic. Neuropsychiatric conditions such as autism spectrum disorders (ASD), intellectual disability (ID), and attention deficit hyperactivity disorders (ADHD) are common NDDs characterized by their hereditary underpinnings and inherent heterogeneity. Genetic risk factors for NDDs are increasingly being identified in non-coding regions and proteins bound to them, including transcriptional regulators and chromatin remodelers. Importantly, de novo mutations are emerging as important contributors to NDDs and neuropsychiatric disorders. Recently, de novo mutations in transcriptional co-factor Zmiz1 or its regulatory regions have been identified in unrelated patients with syndromic ID and ASD. However, the role of Zmiz1 in brain development is unknown. Here, using publicly available databases and a Zmiz1 mutant mouse model, we reveal that Zmiz1 is highly expressed during embryonic brain development in mice and humans, and though broadly expressed across the brain, Zmiz1 is enriched in areas prominently impacted in ID and ASD such as cortex, hippocampus, and cerebellum. We investigated the relationship between Zmiz1 structure and pathogenicity of protein variants, the epigenetic marks associated with Zmiz1 regulation, and protein interactions and signaling pathways regulated by Zmiz1. Our analysis reveals that Zmiz1 regulates multiple developmental processes, including neurogenesis, neuron connectivity, and synaptic signaling. This work paves the way for future studies on the functions of Zmiz1 and highlights the importance of combining analysis of mouse models and human data.
Does the frequency of eating snacks increase food waste? A study based on senior high school in China
Authors: Zhang Panpan , Zhang Weijie , Liu Xiaojie , Sun Fangyuan
Published: April 2024

Food waste is increasingly becoming a global challenge, and school canteens are a significant and severe source of food waste. Reducing food waste is conducive to ensuring food security and environmental sustainability. A good understanding on the influencing factors of food waste is a prerequisite for exploring effective measures to reduce food waste. We obtained senior high school first-hand food waste data through field survey using the methods of face-to-face interview, questionnaire survey, and direct weighing in September 2019. Our survey data showed that the per capita per meal food waste of senior high school students (SHSS) was 44.48 g. The specific performance was as follows: the per capita per meal food waste of breakfast, lunch, and dinner was 22.39, 55.28, and 54.24 g, respectively. The empirical results showed that the frequency of eating snacks had a significant effect on whether the SHSS had food waste behavior and significantly affected the amount of food waste by SHSS. With the increased frequency of eating snacks, the food waste probability was increased and the amount of food waste was greater. This study suggested that we could eat snacks but reduced the frequency of eating snacks to achieve the goal of mitigating food waste. This was a simple and effective way to reduce food waste.