bluuebunny/crossref_metadata_2025 huggingface dataset:
Training doctoral students in critical thinking and experimental design using problem-based learning
Authors: Schaller Michael D. , Gencheva Marieta , Gunther Michael R. , Weed Scott A.
Published: August 2023

Background

Traditionally, doctoral student education in the biomedical sciences relies on didactic coursework to build a foundation of scientific knowledge and an apprenticeship model of training in the laboratory of an established investigator. Recent recommendations for revision of graduate training include the utilization of graduate student competencies to assess progress and the introduction of novel curricula focused on development of skills, rather than accumulation of facts. Evidence demonstrates that active learning approaches are effective. Several facets of active learning are components of problem-based learning (PBL), which is a teaching modality where student learning is self-directed toward solving problems in a relevant context. These concepts were combined and incorporated in creating a new introductory graduate course designed to develop scientific skills (student competencies) in matriculating doctoral students using a PBL format.

Methods

Evaluation of course effectiveness was measured using the principals of the Kirkpatrick Four Level Model of Evaluation. At the end of each course offering, students completed evaluation surveys on the course and instructors to assess their perceptions of training effectiveness. Pre- and post-tests assessing students’ proficiency in experimental design were used to measure student learning.

Results

The analysis of the outcomes of the course suggests the training is effective in improving experimental design. The course was well received by the students as measured by student evaluations (Kirkpatrick Model Level 1). Improved scores on post-tests indicate that the students learned from the experience (Kirkpatrick Model Level 2). A template is provided for the implementation of similar courses at other institutions.

Conclusions

This problem-based learning course appears effective in training newly matriculated graduate students in the required skills for designing experiments to test specific hypotheses, enhancing student preparation prior to initiation of their dissertation research.
Clinical leadership and coping strategies in times of COVID-19: observational study with health managers in Mendoza
Authors: Gil-Hernández Eva , Falaschi Andrea , Carrillo Irene , Rodríguez Viviana , Peralta Roca María Belén , García-Elorrio Ezequiel , Mira José Joaquín
Published: August 2023

Background

The outbreak of the COVID-19 pandemic required an immediate response to the healthcare challenges it posed. This study was conducted to identify actions that helped healthcare professionals to overcome the initial impact in Mendoza (Argentina).

Methods

A cross-sectional study was carried out in a non-random sample of managers and staff of the public health system of Mendoza (Argentina) (n = 134). An ad-hoc and voluntary survey was carried out with 5 multi-response questions that combined questions referring to the management of the pandemic at the organizational level with others referring to coping at the individual level. The survey questions were formulated based on the results of six focus groups that were conducted previously. Descriptive frequency analysis was performed.

Results

60 people agreed to participate and 45 answered the full questionnaire. At both the organizational and individual level, there was consensus with at least 50% of votes. The most outstanding at the organizational level was “Prioritize the need according to risk” and at the individual level it was “Support from family or friends”, being also the most voted option in the whole questionnaire.

Conclusions

The responses that emerged for coping with COVID-19 must be seen as an opportunity to identify strategies that could be effective in addressing future crisis situations that jeopardize the system’s response capacity. Moreover, it is essential to retain both changes at the organizational level (e.g., new protocols, multidisciplinary work, shift restructuring, etc.) and coping strategies at the individual level (e.g., social support, leisure activities, etc.) that have proven positive outcomes.
Proceedings from the CIHLMU 2022 Symposium: “Availability of and Access to Quality Data in Health”
Authors: Tuladhar Sabita , Mwamelo Kimothy , Manyama Christina , Obuobi Dorothy , Antunes Mario , Gashaw Mulatu , Vogel Monica , Shrinivasan Harinee , Mugambwa Kashung Annie , Korley Isabella , Froeschl Guenter , Hoffaeller Lisa , Scholze Sarah
Published: August 2023

Data is an essential tool for valid and reliable healthcare management. Access to high-quality data is critical to ensuring the early identification of problems, the design of appropriate interventions, and the effective implementation and evaluation of health intervention outcomes. During the COVID-19 pandemic, the need for strong information systems and the value of producing high-quality data for timely response and tracking resources and progress have been very evident across countries. The availability of and access to high-quality data at all levels of the health systems of low and middle-income countries is a challenge, which is exacerbated by multiple parallels and poorly integrated data sources, a lack of data-sharing standards and policy frameworks, their weak enforcement, and inadequate skills among those handling data. Completeness, accuracy, integrity, validity, and timeliness are challenges to data availability and use. “Big Data” is a necessity and a challenge in the current complexities of health systems. In transitioning to digital systems with proper data standards and policy frameworks for privacy protection, data literacy, ownership, and data use at all levels of the health system, skill enhancement of the staff is critical. Adequate funding for strengthening routine information systems and periodic surveys and research, and reciprocal partnerships between high-income countries and low- and middle-income countries in data generation and use, should be prioritized by the low- and middle-income countries to foster evidence-based healthcare practices.
PRM-based quantitative proteomics analysis of altered HSP abundance in villi and decidua of patients with early missed abortion
Authors: Chen Xiao-Fang , Chen Xiao-Qing , Luo Hai-Lian , Xia Li-Na , Huang Shu-Hui , Chen Qi
Published: August 2023

Objective

In this study, we aimed to identify differentially expressed heat shock protein (HSP) profiles in the villi and decidua from patients with early missed abortion (EMA).

Methods

By using high-throughput and high-precision parallel reaction monitoring (PRM)-based targeted proteomics techniques, this study examined the abundance of HSPs in the villi and decidua of 10 patients with EMA and 10 controls. Moreover, the abundance of 3 HSPs in the villi of another 22 patients with EMA and 22 controls was verified with Western blotting and immunohistochemistry (IHC).

Results

There were potential differences in the abundance of 16 HSPs and 42 polypeptides in human villi and decidua compared with those of the control group. Among them, HSP90AB1, HSPD1 and HSPA13 were downregulated in abundance in villi of patients with EMA, with a statistically significant difference, which was consistent with the verification results of Western blots and IHC.

Conclusion

Using a PRM-based targeted proteomics technique, this study is the first to screen and quantitatively analyze the expression profile of HSPs in the villi and decidua of patients with EMA. The significant downregulation of HSP90AB1, HSPD1 and HSPA13 was found to have a potentially intimate association with the occurrence of EMA. The findings in our study may provide novel potential research targets related to HSPs for the pathogenesis, prevention and treatment of EMA.
Double counting of clients using services in Iran: implications for assessing the reach of harm reduction programs
Authors: Tavakoli Fatemeh , Mcfarland Willi , Ghalekhani Nima , Khezri Mehrdad , Haghdoost Ali Akbar , Gouya Mohammad Mehdi , Mahboobi Marzieh , Hosseionpour Ali Mohammad , Komasi Ali , Ghorbanian Mehdi , Nasiri Moghadam Nasim , Taghipour Maryam , Sharifi Hamid
Published: August 2023

Background

Many people with high-risk sexual or injection behaviors use harm reduction services with different identities and are therefore counted more than once in client databases. This practice results in inaccurate statistics on the number of clients served and the effective reach of these services. This study aimed to determine the levels of double counting of clients of harm reduction services, including needle and syringe programs, condom distribution, HIV testing and counseling, and methadone maintenance in five cities in Iran.

Methods

Between September and March 2020, our study included 1630 clients, 115 staff of harm reduction centers, and 30 experts in the field of harm reduction in five cities in Iran. Clients of harm reduction services were asked about using harm reduction services multiple times at the same center or at different centers in the last year using different identities. Estimates of double counting derived from client responses were validated by panels of center staff and experts in harm reduction.

Results

Synthesizing data from clients, staff, and experts, the final estimates of double counting of clients using harm reduction services were: HIV testing 10% (95% confidence interval [CI] 0–15), needle and syringe programs 17% (95% CI 8.5–20), condom distribution programs 13% (95% CI 3–19), HIV/STI counseling 10% (95% CI 0–16), and methadone maintenance 7% (95% CI 2–10).

Conclusion

Double counting of clients in harm reduction services in Iran is substantial. Data on clients reach by harm reduction services need to be corrected for double counting to improve program planning, client population size estimation, and efficient resource allocation.
Postoperative recurrence in locally advanced rectal cancer: how does neoadjuvant treatment affect recurrence pattern?
Authors: Okamura Ryosuke , Itatani Yoshiro , Fujita Yusuke , Hoshino Nobuaki , Okumura Shintaro , Nishiyama Kazuhiro , Hida Koya , Obama Kazutaka
Published: August 2023

Background

The treatment strategy for locally advanced rectal cancer (LARC) has recently expanded from total mesorectal excision to additional neoadjuvant chemoradiotherapy (nCRT) and/or systemic chemotherapy (NAC). Data on disease recurrence after each treatment strategy are limited.

Methods

Clinical stage II to III rectal cancer patients who underwent curative surgery between July 2005 and February 2021 were analyzed. The cumulative incidence and site of first recurrence were assessed. The median follow-up duration was 4.6 years.

Results

Among the 332 patients, we performed nCRT and NAC in 15.4% (N=51) and 14.8% (N=49), respectively. The overall recurrence rate was 23.5% (N=78). Although several differences in tumor stage or location were observed, there was no significant difference in the rate among the surgery alone (N=54, 23.3%), nCRT (N=11, 21.6%), and NAC (N=13, 26.5%) groups. In this cohort, the local recurrence rate (18.4%) was higher than the rate of distant metastasis in the NAC group (14.3%). All patients with recurrence in the nCRT group had distant metastases (N=11: one patient had distant and local recurrences simultaneously). For pathological stage 0-I, the recurrence rate was higher in the nCRT and NAC groups than in the surgery-alone group (nCRT, 10.0%; NAC, 15.4%; and surgery-alone, 2.0%). Curative-intent resection of distant-only recurrences significantly improved patients’ overall survival (hazard ratio [95% confidence interval], 0.34 [0.14–0.84]), which was consistent even when stratified according to neoadjuvant treatment. Regardless of neoadjuvant treatment, >80% of recurrences occurred in the first 2.2 years, and 98.7% within 5 years after surgery.

Conclusion

Regardless of neoadjuvant treatment, detecting distant metastases with intensive surveillance, particularly in the first 2 years after surgery, is important. Also, even if neoadjuvant treatment can downstage LARC to pathological stage 0-I, careful follow-up is needed.
Characterization of the skin keloid microenvironment
Authors: Zhang Mengwen , Chen Hailong , Qian Huan , Wang Chen
Published: August 2023

Keloids are a fibroproliferative skin disorder that develops in people of all ages. Keloids exhibit some cancer-like behaviors, with similar genetic and epigenetic modifications in the keloid microenvironment. The keloid microenvironment is composed of keratinocytes, fibroblasts, myofibroblasts, vascular endothelial cells, immune cells, stem cells and collagen fibers. Recent advances in the study of keloids have led to novel insights into cellular communication among components of the keloid microenvironment as well as potential therapeutic targets for treating keloids. In this review, we summarized the nature of genetic and epigenetic regulation in keloid-derived fibroblasts, epithelial-to-mesenchymal transition of keratinocytes, immune cell infiltration into keloids, the differentiation of keloid-derived stem cells, endothelial-to-mesenchymal transition of vascular endothelial cells, extracellular matrix synthesis and remodeling, and uncontrolled angiogenesis in keloids with the aim of identifying new targets for therapeutic benefit.
Bone mesenchymal stem cell extracellular vesicles delivered miR let-7-5p alleviate endothelial glycocalyx degradation and leakage via targeting ABL2
Authors: Li Zhe , Xu Yuqing , Lu Shiyue , Gao Yuan , Deng Yuxiao
Published: August 2023

Background

Endothelial glycocalyx (EG) is an active player and treatment target in inflammatory-related vascular leakage. The bone marrow mesenchymal stem cells (bMSCs) are promising potential treatments for leakage; however, the therapeutic effect and mechanism of bMSC on EG degradation needs to be elucidated.

Methods

EG degradation and leakage were evaluated in both lipopolysaccharide (LPS)-induced mice ear vascular leakage model and LPS-stimulated human umbilical vein endothelial cells (HUVECs) model treated with bMSCs. Extracellular vesicles (EVs) were extracted from bMSCs and the containing microRNA profile was analyzed. EV and miR let-7-5p were inhibited to determine their function in the therapeutic process. The ABL2 gene was knockdown in HUVECs to verify its role as a therapeutic target in EG degradation.

Results

bMSCs treatment could alleviate LPS-induced EG degradation and leakage in vivo and in vitro, whereas EVs/let-7-5p-deficient bMSCs were insufficient to reduce EG degradation. LPS down-regulated the expression of let-7-5p while upregulated endothelial expression of ABL2 in HUVECs and induced EG degradation and leakage. bMSC-EVs uptaken by HUVECs could deliver let-7-5p targeting endothelial ABL2, which suppressed the activation of downstream p38MAPK and IL-6, IL-1β levels, and thus reversed LPS-induced EG degradation and leakage.

Conclusion

bMCSs alleviate LPS-induced EG degradation and leakage through EV delivery of miR let-7-5p targeting endothelial ABL2.
Integrated multi-omics analyses reveal Jorunnamycin A as a novel suppressor for muscle-invasive bladder cancer by targeting FASN and TOP1
Authors: Chen Ruijiao , Hao Xiaopeng , Chen Jingyuan , Zhang Changyue , Fan Huixia , Lian Fuming , Chen Xiaochuan , Wang Chao , Xia Yong
Published: August 2023

Background

Bladder cancer is a urological carcinoma with high incidence, among which muscle invasive bladder cancer (MIBC) is a malignant carcinoma with high mortality. There is an urgent need to develop new drugs with low toxicity and high efficiency for MIBC because existing medication has defects, such as high toxicity, poor efficacy, and side effects. Jorunnamycin A (JorA), a natural marine compound, has been found to have a high efficiency anticancer effect, but its anticancer function and mechanism on bladder cancer have not been studied.

Methods

To examine the anticancer effect of JorA on MIBC, Cell Counting Kit 8, EdU staining, and colony formation analyses were performed. Moreover, a xenograft mouse model was used to verify the anticancer effect in vivo. To investigate the pharmacological mechanism of JorA, high-throughput quantitative proteomics, transcriptomics, RT-qPCR, western blotting, immunofluorescence staining, flow cytometry, pulldown assays, and molecular docking were performed.

Results

JorA inhibited the proliferation of MIBC cells, and the IC50 of T24 and UM-UC-3 was 0.054 and 0.084 μM, respectively. JorA-induced significantly changed proteins were enriched in “cancer-related pathways” and “EGFR-related signaling pathways”, which mainly manifested by inhibiting cell proliferation and promoting cell apoptosis. Specifically, JorA dampened the DNA synthesis rate, induced phosphatidylserine eversion, and inhibited cell migration. Furthermore, it was discovered that fatty acid synthase (FASN) and topoisomerase 1 (TOP1) are the JorA interaction proteins. Using DockThor software, the 3D docking structures of JorA binding to FASN and TOP1 were obtained (the binding affinities were − 8.153 and − 7.264 kcal/mol, respectively).

Conclusions

The marine compound JorA was discovered to have a specific inhibitory effect on MIBC, and its potential pharmacological mechanism was revealed for the first time. This discovery makes an important contribution to the development of new high efficiency and low toxicity drugs for bladder cancer therapy.

Graphical Abstract
Warburg effect enhanced by AKR1B10 promotes acquired resistance to pemetrexed in lung cancer-derived brain metastasis
Authors: Duan Wenzhe , Liu Wenwen , Xia Shengkai , Zhou Yang , Tang Mengyi , Xu Mingxin , Lin Manqing , Li Xinyu , Wang Qi
Published: August 2023

Background

Resistance to pemetrexed (PEM), a rare chemotherapeutic agent that can efficiently cross the blood-brain barrier, limits the therapeutic efficacy for patients with lung cancer brain metastasis (BM). Aldo-keto reductase family 1 B10 (AKR1B10) was recently found to be elevated in lung cancer BM. The link between AKR1B10 and BM-acquired PEM is unknown.

Methods

PEM drug-sensitivity was assessed in the preclinical BM model of PC9 lung adenocarcinoma cells and the BM cells with or without AKR1B10 interference in vitro and in vivo. Metabolic reprogramming of BM attributed to AKR1B10 was identified by chromatography-mass spectrometry (GC-MS) metabolomics, and the mechanism of how AKR1B10 mediates PEM chemoresistance via a way of modified metabolism was revealed by RNA sequencing as well as further molecular biology experimental approaches.

Results

The lung cancer brain metastatic subpopulation cells (PC9-BrM3) exhibited significant resistance to PEM and silencing AKR1B10 in PC9-BrM3 increased the PEM sensitivity in vitro and in vivo. Metabolic profiling revealed that AKR1B10 prominently facilitated the Warburg metabolism characterized by the overproduction of lactate. Glycolysis regulated by AKR1B10 is vital for the resistance to PEM. In mechanism, AKR1B10 promoted glycolysis by regulating the expression of lactate dehydrogenase (LDHA) and the increased lactate, acts as a precursor that stimulates histone lactylation (H4K12la), activated the transcription of CCNB1 and accelerated the DNA replication and cell cycle.

Conclusions

Our finding demonstrates that AKR1B10/glycolysis/H4K12la/CCNB1 promotes acquired PEM chemoresistance in lung cancer BM, providing novel strategies to sensitize PEM response in the treatment of lung cancer patients suffering from BM.
Stargardt disease-associated in-frame ABCA4 exon 17 skipping results in significant ABCA4 function
Authors: Kaltak Melita , Blanco-Garavito Rocio , Molday Laurie L. , Dhaenens Claire-Marie , Souied Eric E. , Platenburg Gerard , Swildens Jim , Molday Robert S. , Cremers Frans P. M.
Published: August 2023

Background

ABCA4, the gene implicated in Stargardt disease (STGD1), contains 50 exons, of which 17 contain multiples of three nucleotides. The impact of in-frame exon skipping is yet to be determined. Antisense oligonucleotides (AONs) have been investigated in Usher syndrome-associated genes to induce skipping of in-frame exons carrying severe variants and mitigate their disease-linked effect. Upon the identification of a STGD1 proband carrying a novel exon 17 canonical splice site variant, the activity of ABCA4 lacking 22 amino acids encoded by exon 17 was examined, followed by design of AONs able to induce exon 17 skipping.

Methods

A STGD1 proband was compound heterozygous for the splice variant c.2653+1G>A, that was predicted to result in in-frame skipping of exon 17, and a null variant [c.735T>G, p.(Tyr245*)]. Clinical characteristics of this proband were studied using multi-modal imaging and complete ophthalmological examination. The aberrant splicing of c.2653+1G>A was investigated in vitro in HEK293T cells with wild-type and mutant midigenes. The residual activity of the mutant ABCA4 protein lacking Asp864-Gly885 encoded by exon 17 was analyzed with all-trans-retinal-activated ATPase activity assay, along with its subcellular localization. To induce exon 17 skipping, the effect of 40 AONs was examined in vitro in WT WERI-Rb-1 cells and 3D human retinal organoids.

Results

Late onset STGD1 in the proband suggests that c.2653+1G>A does not have a fully deleterious effect. The in vitro splice assay confirmed that this variant leads to ABCA4 transcripts without exon 17. ABCA4 Asp864_Gly863del was stable and retained 58% all-trans-retinal-activated ATPase activity compared to WT ABCA4. This sequence is located in an unstructured linker region between transmembrane domain 6 and nucleotide-binding domain-1 of ABCA4. AONs were designed to possibly reduce pathogenicity of severe variants harbored in exon 17. The best AON achieved 59% of exon 17 skipping in retinal organoids.

Conclusions

Exon 17 deletion in ABCA4 does not result in the absence of protein activity and does not cause a severe STGD1 phenotype when in trans with a null allele. By applying AONs, the effect of severe variants in exon 17 can potentially be ameliorated by exon skipping, thus generating partial ABCA4 activity in STGD1 patients.

Graphical abstract
Platelet-derived circRNAs signature in patients with gastroenteropancreatic neuroendocrine tumors
Authors: Campolo Federica , Sesti Franz , Feola Tiziana , Puliani Giulia , Faggiano Antongiulio , Tarsitano Maria Grazia , Tenuta Marta , Hasenmajer Valeria , Ferretti Elisabetta , Verrico Monica , Gianfrilli Daniele , Venneri Mary Anna , Isidori Andrea M. , Giannetta Elisa
Published: August 2023

Background

Neuroendocrine tumors (NETs) early diagnosis is a clinical challenge that require a deep understanding of molecular and genetic features of this heterogeneous group of neoplasms. However, few biomarkers exist to aid diagnosis and to predict prognosis and treatment response. In the oncological field, tumor-educated platelets (TEPs) have been implicated as central players in the systemic and local responses to tumor growth, thereby altering tumor specific RNA profile. Although TEPs have been found to be enriched in RNAs, few studies have investigated the potential of a type of RNA, circular RNAs (circRNA), as platelet-derived biomarkers for cancer. In this proof-of-concept study, we aim to demonstrate whether the circRNAs signature of tumor educated platelets can be used as a liquid biopsy biomarker for the detection of gastroenteropancreatic (GEP)-NETs and the prediction of the early response to treatment.

Methods

We performed a 24-months, prospective proof-of-concept study in men and women with histologically proven well-differentiated G1-G2 GEP-NET, aged 18–80 years, naïve to treatment. We performed a RNAseq analysis of circRNAs obtained from TEPs samples of 10 GEP-NETs patients at baseline and after 3 months from therapy (somatostatin analogs or surgery) and from 5 patients affected by non-malignant endocrinological diseases enrolled as a control group.

Results

Statistical analysis based on p < 0.05 resulted in the identification of 252 circRNAs differentially expressed between GEP-NET and controls of which 109 were up-regulated and 143 were down-regulated in NET patients. Further analysis based on an FDR value ≤ 0.05 resulted in the selection of 5 circRNAs all highly significant downregulated. The same analysis on GEP-NETs at baseline and after therapy in 5 patients revealed an average of 4983 remarkably differentially expressed circRNAs between follow-up and baseline samples of which 2648 up-regulated and 2334 down-regulated, respectively. Applying p ≤ 0.05 and FDR ≤ 0.05 filters, only 3/5 comparisons gave statistically significant results.

Conclusions

Our findings identified for the first time a circRNAs signature from TEPs as potential diagnostic and predictive biomarkers for GEP-NETs.
Multi-target regulatory mechanism of Yang Xin Tang − a traditional Chinese medicine against dementia
Authors: Lo Tung Yan , Chan Anthony Siu Lung , Cheung Suet Ting , Yung Lisa Ying , Leung Manton Man Hon , Wong Yung Hou
Published: August 2023

Background

Yang Xin Tang (YXT) is a traditional Chinese herbal preparation which has been reported to improve cognitive function and memory in patients with dementia. As the underlying mechanism of action of YXT has not been elucidated, we examined the effects of YXT and its major herbal components in regulating gene transcription and molecular targets related to Alzheimer’s disease (AD).

Methods

Aqueous and ethanol extracts of YXT and selected herbal components were prepared and validated by standard methods. A series of biochemical and cellular assays were employed to assess the ability of the herbal extracts to inhibit acetylcholinesterase, reduce β-amyloid aggregation, stimulate the differentiation of neural progenitor cells, suppress cyclooxygenase, and protect neurons against β-amyloid or N-methyl-D-aspartate-induced cytotoxicity. The effects of YXT on multiple molecular targets were further corroborated by a panel of nine reporter gene assays.

Results

Extracts of YXT and two of its constituent herbs, Poria cocos and Poria Sclerotium pararadicis, significantly inhibited β-amyloid aggregation and β-amyloid-induced cytotoxicity. A protective effect of the YXT extract was similarly observed against N-methyl-D-aspartate-induced cytotoxicity in primary neurons, and this activity was shared by extracts of Radix Astragali and Rhizoma Chuanxiong. Although the YXT extract was ineffective, extracts of Poria cocos, Poria Sclerotium pararadicis and Radix Polygalae inhibited acetylcholine esterase, with the latter also capable of upregulating choline acetyltransferase. YXT and its components significantly inhibited the activities of the pro-inflammatory cyclooxygenases. Additionally, extracts of YXT and several of its constituent herbs significantly stimulated the phosphorylation of extracellular signal-regulated kinases and cAMP-responsive element binding protein, two molecular targets involved in learning and memory, as well as in the regulation of neurogenesis.

Conclusions

Several constituents of YXT possess multiple regulatory effects on known therapeutic targets of AD that range from β-amyloid to acetylcholinesterase. The demonstrated neuroprotective and neurogenic actions of YXT lend credence to its use as an alternative medicine for treating AD.
Impact of dienogest pretreatment on IVF-ET outcomes in patients with endometriosis: a systematic review and meta-analysis
Authors: Shao Wenjing , Li Yuying , Wang Yanli
Published: August 2023

Background

To comprehensively evaluate the influence of dienogest (DNG) versus non-DNG pretreatment on in vitro fertilization and embryo transfer (IVF-ET) outcomes for patients with endometriosis.

Methods

PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, and VIP were comprehensively searched for relevant publications until September 14, 2022. Primary outcomes included clinical pregnancy rate and live birth rate. Secondary outcomes included retrieved oocytes, mature oocytes, blastocysts, growing follicles, transferrable embryos, fertilization rate, implantation rate, and miscarriage rate. Subgroup analysis was performed according to different grouping methods and embryo types.

Results

Five studies of 568 females with endometriosis were involved in this systematic review and meta-analysis. DNG treatment exhibited similar effects to non-DNG treatment on either the primary or the secondary outcomes (all P > 0.05). The DNG group had a significantly greater clinical pregnancy rate than the non-hormonal treatment group (pooled relative risk [RR]: 2.055, 95% confidence interval [CI]: 1.275, 3.312, P = 0.003), and exhibited a significantly lower clinical pregnancy rate than the long gonadotropin-releasing hormone agonist (GnRH-a) group (RR: 0.542, 95%CI: 0.321, 0.916, P = 0.022). For patients undergoing fresh embryo transfer, the DNG group displayed a significantly greater clinical pregnancy rate versus the non-DNG group (pooled RR: 1.848, 95%CI: 1.234, 2.767, P = 0.003). Patients receiving DNG had a significantly greater live birth rate than those with non-hormonal treatment (pooled RR: 2.136, 95%CI: 1.223, 3.734, P = 0.008), while having a significantly lower live birth rate than the long GnRH-a group (RR: 0.441, 95%CI: 0.214, 0.907, P = 0.026). While using fresh embryos, patients with DNG treatment had an increased live birth rate, compared with those without DNG treatment (pooled RR: 2.132, 95%CI: 1.090, 4.169, P = 0.027).

Conclusion

DNG treatment may have similar effects to non-DNG treatment on IVF-ET outcomes. The clinical pregnancy rate and live birth rate after DNG treatment may be significantly higher than those after non-hormonal treatment. More evidence is warranted to corroborate these findings.
Biosynthesis approach of zinc oxide nanoparticles for aqueous phosphorous removal: physicochemical properties and antibacterial activities
Authors: Khamis Mona , Gouda Gamal A. , Nagiub Adham M.
Published: August 2023

In this study, phosphorus (PO43–-P) is removed from water samples using zinc oxide nanoparticles (ZnO NPs). These nanoparticles are produced easily, quickly, and sustainably using Onion extracts (Allium cepa) at an average crystallite size of 8.13 nm using the Debye–Scherrer equation in the hexagonal wurtzite phase. The characterization and investigation of bio-synthesis ZnO NPs were carried out. With an initial concentration of 250 mg/L of P, the effects of the adsorbent dose, pH, contact time, and temperature were examined. At pH = 3 and T = 300 K, ZnO NPs achieved the optimum sorption capacity of 84 mg/g, which was superior to many other adsorbents. The isothermal study was found to fit the Langmuir model at a monolayer capacity of 89.8 mg/g, and the kinetic study was found to follow the pseudo-second-order model. The adsorption process was verified to be endothermic and spontaneous by thermodynamic characteristics. As a result of their low cost as an adsorbent and their high metal absorption, ZnO NPs were found to be the most promising sorbent in this investigation and have the potential to be used as effective sorbents for the removal of P from aqueous solutions. The antimicrobial activity results showed that ZnO NPs concentration had greater antibacterial activity than conventional Cefotaxime, which was utilized as a positive control in the inhibitory zone. However, no inhibitory zone was visible in the controlled wells that had been supplemented with onion extract and DMSO.
Multilayer omics reveals the molecular mechanism of early infection of Clonorchis sinensis juvenile
Authors: Wu Yuhong , Deng Xueling , Wu Zhanshuai , Liu Dengyu , Fu Xiaoyin , Tang Lili , He Shanshan , Lv Jiahui , Wang Jilong , Li Qing , Zhan Tingzheng , Tang Zeli
Published: August 2023

Background

Clonorchiasis remains a non-negligible global zoonosis, causing serious socioeconomic burdens in endemic areas. Clonorchis sinensis infection typically elicits Th1/Th2 mixed immune responses during the course of biliary injury and periductal fibrosis. However, the molecular mechanism by which C. sinensis juvenile initially infects the host remains poorly understood.

Methods

The BALB/c mouse model was established to study early infection (within 7 days) with C. sinensis juveniles. Liver pathology staining and observation as well as determination of biochemical enzymes, blood routine and cytokines in blood were conducted. Furthermore, analysis of liver transcriptome, proteome and metabolome changes was performed using multi-omics techniques. Statistical analyses were performed using Student's t-test.

Results

Histopathological analysis revealed that liver injury, characterized by collagen deposition and inflammatory cell infiltration, occurred as early as 24 h of infection. Blood indicators including ALT, AST, WBC, CRP and IL-6 indicated that both liver injury and systemic inflammation worsened as the infection progressed. Proteomic data showed that apoptosis and junction-related pathways were enriched within 3 days of infection, indicating the occurrence of liver injury. Furthermore, proteomic and transcriptomic analysis jointly verified that the detoxification and antioxidant defense system was activated by enrichment of glutathione metabolism and cytochrome P450-related pathways in response to acute liver injury. Proteomic-based GO analysis demonstrated that biological processes such as cell deformation, proliferation, migration and wound healing occurred in the liver during the early infection. Correspondingly, transcriptomic results showed significant enrichment of cell cycle pathway on day 3 and 7. In addition, the KEGG analysis of multi-omics data demonstrated that numerous pathways related to immunity, inflammation, tumorigenesis and metabolism were enriched in the liver. Besides, metabolomic screening identified several metabolites that could promote inflammation and hepatobiliary periductal fibrosis, such as CA7S.

Conclusions

This study revealed that acute inflammatory injury was rapidly triggered by initial infection by C. sinensis juveniles in the host, accompanied by the enrichment of detoxification, inflammation, fibrosis, tumor and metabolism-related pathways in the liver, which provides a new perspective for the early intervention and therapy of clonorchiasis.

Graphical Abstract
Effect of guselkumab on serum biomarkers in patients with active psoriatic arthritis and inadequate response to tumor necrosis factor inhibitors: results from the COSMOS phase 3b study
Authors: Schett Georg , Chen Warner , Gao Sheng , Chakravarty Soumya D. , Shawi May , Lavie Frederic , Zimmermann Miriam , Sharaf Mohamed , Coates Laura C. , Siebert Stefan
Published: August 2023

Background

Guselkumab is a selective interleukin (IL)-23 inhibitor targeting the IL-23p19 subunit. In the phase 3b COSMOS trial, guselkumab demonstrated efficacy in treating participants with active psoriatic arthritis (PsA) and inadequate response (IR; lack of efficacy or intolerance) to tumor necrosis factor inhibitors (TNFi).

Methods

Adults with active PsA (≥ 3 swollen joints,  ≥ 3 tender joints) and IR to one or two TNFi (TNFi-IR) were randomized 2:1 to guselkumab at Weeks 0, 4, then every 8 weeks (Q8W) or placebo➔guselkumab Q8W at Week 24 with possible early escape at Week 16. Levels of serum cytokines, including interferon γ (IFNγ), IL-10, and tumor necrosis factor α (TNFα); T helper 17 (Th17) effector cytokines IL-17A, IL-17F, and IL-22; and acute phase proteins C-reactive protein (CRP), IL-6, and serum amyloid A (SAA), were assessed and compared with demographically matched healthy controls; guselkumab pharmacodynamics through Week 24 were also assessed. Associations between baseline biomarker levels and 1) baseline disease activity (28-joint disease activity score using CRP [DAS28-CRP], psoriasis area and severity index [PASI], and % body surface area [BSA] affected by psoriasis) and 2) clinical response (including  ≥ 20% improvement in American College of Rheumatology criteria [ACR20] response) at Week 24 were assessed.

Results

Baseline serum levels of IL-6, IL-10, IL-17A, IL-17F, IL-22, TNFα, and IFNγ were significantly higher in COSMOS TNFi-IR participants than in healthy controls. Baseline IL-6, CRP, and SAA levels were associated with baseline DAS28-CRP. IL-17A and IL-17F levels were associated with baseline PASI score and psoriasis BSA. Baseline swollen or tender joint counts did not associate with baseline biomarker levels. At Week 24, significant decreases from baseline in CRP, SAA, IL-17A, IL-17F, and IL-22 levels were seen in guselkumab-, but not placebo-, treated participants. IL-17F and IL-22 levels at Week 24 in guselkumab-treated participants did not significantly differ from those of healthy controls. Guselkumab-treated participants achieving ACR20 response at Week 24 exhibited higher baseline IL-22 and IFNγ levels versus nonresponders.

Conclusions

Results from COSMOS participants with active, TNFi-IR PsA suggest guselkumab reduces levels of effector cytokines associated with the IL-23/IL-17 pathway, including those associated with baseline arthritis and skin disease activity.

Trial registration

ClinicalTrials.gov: NCT03796858.
Analysis of inter-joint coordination during the sit-to-stand and stand-to-sit tasks in stroke patients with hemiplegia
Authors: He Jian , Liu Dongwei , Hou Meijin , Luo Anhua , Wang Shuhao , Ma Ye
Published: August 2023

Background

Inter-joint coordination is an important factor affecting postural stability, and its variability increases after fatigue. This study aimed to investigate the coordination pattern of lower limb joints during the sit-to-stand (Si-St) and stand-to-sit (St-Si) tasks in stroke patients and explore the influence of duration on inter-joint coordination.

Methods

Thirteen stroke hemiplegia patients (five with left paretic and eight right paretic) and thirteen age-matched healthy subjects were recruited. The Si-St and St-Si tasks were performed while each subject’s joint kinematics were recorded using a three-dimensional motion capture system. Sagittal joint angles of the bilateral hip, knee and ankle joints as well as the movement duration were extracted. The angle-angle diagrams for the hip-knee, hip-ankle and knee-ankle joint were plotted to assess the inter-joint coordination. The inter-joint coordination was quantified using geometric characteristics of the angle-angle diagrams, including perimeter, area and dimensionless ratio. The coefficient of variation (CV) was performed to compare variability of the coordination parameters.

Results

There were no significant differences in the perimeter, area and dimensionless ratio values of the bilateral hip-knee, hip-ankle and knee-ankle inter-joints during Si-St and St-Si tasks in the stroke group. The perimeter values of bilateral hip-knee and knee-ankle inter-joints in the stroke group were lower (P<0.05) than in the healthy group during Si-St and St-Si tasks. Although no significant bilateral differences were found, the inter-joint coordination in stroke patients decreased with the increased movement duration of both Si-St and St-Si tasks. Additionally, the CV of the hip-knee inter-joint area during the Si-St task in the stroke group was less than (P<0.05) that in the healthy group.

Conclusion

Stroke patients exhibit different inter-joint coordination patterns than healthy controls during the Si-St and St-Si tasks. The duration affects joint coordination, and inter-joint coordination is limited on the hemiplegic side joint pairs, which may lead to inconsistency in the rhythm of the left and right leg inter-joint movements and increase the risk of falls. These findings provide new insights into motor control rehabilitation strategies and may help planning targeted interventions for stoke patients with hemiplegia.
Polyagglutinability phenomenon: a case report and review of the literature
Authors: Azzi Noussaiba , Trougouty Nabiha , seddik Rachid
Published: August 2023

Background

Polyagglutinability of red blood cells is a rare immunological phenomenon, it is due to a cryptic antigen that is abnormally present on the surface of red blood cells. The aim of our work is to shed light on polyagglutinability, which is still poorly understood cause of discordance between the cell and serum tests and can sometimes have harmful transfusion consequences.

Case presentation

We report the case of a 70-year-old African patient admitted for management of hemolytic anemia.

Results

During the erythrocyte grouping, a discordance between the cell and serum tests was observed, with polyagglutinability for the RH phenotype, a positive AB control, and even a positive control. The direct antiglobulin test and the Coombs test were also positive. The same results were obtained even after washing the red blood cells and incubating them at 37 °C for 30 min. For transfusion purposes, erythrocyte genotyping was performed, and the patient was transfused with an A+ red blood cell unit with an RH Kell-compatible phenotype.

Conclusion

Polyagglutinability should always be taken into account when grouping anomalies are encountered. Although it may not show any symptoms, hemolysis is frequently observed during transfusions.
New results for the upper bounds of the distance between adjacent zeros of first-order differential equations with several variable delays
Authors: Attia Emad R. , El-Matary Bassant M.
Published: August 2023

The distance between consecutive zeros of a first-order differential equation with several variable delays is studied. Here, we show that the distribution of zeros of differential equations with variable delays is not an easy extension of the case of constant delays. We obtain new upper bounds for the distance between zeros of all solutions of a differential equation with several delays, which extend and improve some existing results. Two illustrative examples are given to show the advantages of the proposed results over the known ones.
Bifurcation mechanism and hybrid control strategy of a finance model with delays
Authors: Liu Zixin , Li Wenfang , Xu Changjin , Liu Chunfeng , Mu Dan , Xu Mengzhu , Ou Wei , Cui Qingyi
Published: August 2023

Establishing financial models or economic models to describe economic phenomena in real life has become a heated discussion in society at present. From a mathematical point of view, the exploration on dynamics of financial models or economic models is a valuable work. In this study, we build a new delayed finance model and explore the dynamical behavior containing existence and uniqueness, boundedness of solution, Hopf bifurcation, and Hopf bifurcation control of the considered delayed finance model. By virtue of fixed point theorem, we prove the existence and uniqueness of the solution to the considered delayed finance model. Applying a suitable function, we obtain the boundedness of the solutions for the considered delayed finance model. Taking advantage of the stability criterion and bifurcation argument of delayed differential equation, we establish a delay-independent condition ensuring the stability and generation of Hopf bifurcation of the involved delayed finance model. Exploiting hybrid controller including state feedback and parameter perturbation, we efficaciously adjust the stability region and the time of occurrence of Hopf bifurcation of the involved delayed finance model. The study manifests that time delay is a fundamental parameter in controlling stability region and the time of onset of Hopf bifurcation of the involved delayed finance model. To examine the soundness of established key results, computer simulation figures are concretely displayed. The derived conclusions of this study are perfectly new and has momentous theoretical value in economical operation.
Stability regions of discrete linear periodic systems with delayed feedback controls
Authors: Shin Jong Son , Miyazaki Rinko , Kim Dohan
Published: August 2023

We propose a geometric method to determine the stability region of the zero solution of a linear periodic difference equation via the delayed feedback control (briefly, DFC) with the commuting feedback gain. For the equation, our method is more effective than the Jury criterion. First, we give a relationship, named the C-map theorem, between the characteristic multipliers of an original equation and those of the equation via DFC. Next, we show the existence and m-starlike property, defined in this paper, of an m-closed curve induced from the C-map. Using this result, we prove that the region enclosed by the m-closed curve is the stability region of the zero solution of the equation via DFC.
Investigating and comparing the dimensions of worry of Iranian primiparous women in each trimester of pregnancy
Authors: Mirzaee Foruzan , Hasanpoor-Azghady Seyedeh Batool , Amiri-Farahani Leila
Published: August 2023

Background

Pregnancy and childbirth are considered natural events in the life cycle of women. However, it is also a stressful experience along with physiological and psychological changes. Therefore, it is important to study the dimensions that cause more worry in each of the pregnant trimesters. This study aimed to determine and compare the dimensions of worry of Iranian primiparous women in each trimester of pregnancy.

Methods

This cross-sectional study was conducted on 300 primiparous women (n = 100 in each trimester) referred to seven health centers affiliated with the Iran University of Medical Sciences, Tehran, Iran. The sampling was multistage. We collected data from a demographic and fertility questionnaire and the Cambridge Worry Scale (CWS).

Results

The mean score of worry during the entire pregnancy was 28.16. The mean and standard deviation of the worry score in the first trimester was (27.35 ± 12.22). The second trimester was (27.80 ± 12.53) and the third trimester was (29.34 ± 11.11). The highest mean score of worry in the first and third trimmers was the dimension of own health. The second trimester was the dimension of socio-medical. The lowest mean score of worry in all trimmers was the dimension of relationships. Among CWS-related items, the highest mean score of worry in the first trimester was giving birth (3.34) and the possibility of miscarriage (3.22). In the second trimester was the possibility of going into labour too early (3.3) and the possibility of miscarriage (3.12), and in the third trimester was the possibility of going into labour too early (3.33) and giving birth (3.27). The lowest mean score of worry in all three trimesters was related to problems with the law.

Conclusion

pregnancy worry in the third trimester was more than the other two trimesters, and worrying about own health was the most important dimension of worry for pregnant women. Paying attention to the dimensions of worry of pregnant women helps design appropriate interventions to increase the mental and physical health of pregnant women.