bluuebunny/crossref_metadata_2025 huggingface dataset:
Th1 cells reduce the osteoblast-like phenotype in valvular interstitial cells by inhibiting NLRP3 inflammasome activation in macrophages
Authors: Lu Jing , meng Jiaming , Wu Gang , Wei Wulong , Xie Huabao , Liu Yanli
Published: July 2024

Background and aims

Inflammation is initiates the propagation phase of aortic valve calcification. The activation of NLRP3 signaling in macrophages plays a crucial role in the progression of calcific aortic valve stenosis (CAVS). IFN-γ regulates NLRP3 activity in macrophages. This study aimed to explore the mechanism of IFN-γ regulation and its impact on CAVS progression and valve interstitial cell transdifferentiation.

Methods and results

The number of Th1 cells and the expression of IFN-γ and STAT1 in the aortic valve, spleen and peripheral blood increased significantly as CAVS progressed. To explore the mechanisms underlying the roles of Th1 cells and IFN-γ, we treated CAVS mice with IFN-γ-AAV9 or an anti-IFN-γ neutralizing antibody. While IFN-γ promoted aortic valve calcification and dysfunction, it significantly decreased NLRP3 signaling in splenic macrophages and Ly6C+ monocytes. In vitro coculture showed that Th1 cells inhibited NLPR3 activation in ox-LDL-treated macrophages through the IFN-γR1/IFN-γR2-STAT1 pathway. Compared with untreated medium, conditioned medium from Th1-treated bone marrow–derived macrophages reduced the osteogenic calcification of valvular interstitial cells.

Conclusion

Inhibition of the NLRP3 inflammasome by Th1 cells protects against valvular interstitial cell calcification as a negative feedback mechanism of adaptive immunity toward innate immunity. This study provides a precision medicine strategy for CAVS based on the targeting of anti-inflammatory mechanisms.

Graphical Abstract
Closure Effect of I + II Mixed-mode Crack for EA4T Axle Steel
Authors: Wang Shuancheng , Yang Bing , Zhou Shuwei , Li Jian , Xiao Shoune
Published: July 2024

The crack-closure effect is a crucial factor that affects the crack growth rate and should be considered in simulation analysis and testing. A mixed-mode I + II loading fatigue crack growth test was performed using EA4T axle steel specimens. The variation of the plastic-induced crack closure (PICC) effect and the roughness-induced crack closure (RICC) effect during crack deflection in the mixed-mode is examined in this study. The results show that the load perpendicular to the crack propagation direction hinders the slip effect caused by the load parallel to the crack propagation direction under mixed-mode loading, and the crack deflection is an intuitive manifestation of the interaction between the PICC and RICC. The proportion of the RA value change on the crack side caused by contact friction was reduced by the interaction between PICC and RICC. The roughness of the crack surface before and after the crack deflection is different, and the spatial torsion crack surface is formed during the crack propagation process. With the increase of the crack length, the roughness of the fracture surface increases. During the crack deflection process, the PICC value fluctuates around 0.2, and the RICC value is increased to 0.15.
The influence of geographical location on moisture distribution in wood cross sections: a numerical simulation study using Austria as an example
Authors: Brandstätter Florian , Autengruber Maximilian , Lukacevic Markus , Füssl Josef
Published: July 2024

Wood constantly interacts with the surrounding, locally varying climate, leading to changes in the moisture content. Advanced simulation tools can predict the two-dimensional moisture distributions caused by these changing climate conditions within wood cross sections over time. However, there is a notable absence of systematic simulation results for diverse climatic conditions and various wood cross sections. This study seeks to bridge this gap in research. Here, we present moisture fields in three solid timber and three glued laminated timber cross sections in Austria and show the effect of the location and the altitude on the moisture content distribution. The results reveal decreasing influence of the location on the moisture content development with increasing cross section size, and primarily the altitude affecting the moisture content. In addition, the results are compared with the standard for the design of timber–concrete composite structures (ONR CEN/TS 19103), revealing appropriate values in most of the cases. Only for cross sections with a width of 14 cm and larger, assigned to a specific region, the standard value is assumed underestimated. Furthermore, the distribution of moisture gradients, which are related to the crack depth development, are analyzed for Austria, demonstrating the influence of mountain areas in the moisture gradient development.
Unraveling the interplay of neuroinflammatory signaling between parenchymal and meningeal cells in migraine headache
Authors: Dalkara Turgay , Kaya Zeynep , Erdener Şefik Evren
Published: July 2024

Background

The initiation of migraine headaches and the involvement of neuroinflammatory signaling between parenchymal and meningeal cells remain unclear. Experimental evidence suggests that a cascade of inflammatory signaling originating from neurons may extend to the meninges, thereby inducing neurogenic inflammation and headache. This review explores the role of parenchymal inflammatory signaling in migraine headaches, drawing upon recent advancements.

Body

Studies in rodents have demonstrated that sterile meningeal inflammation can stimulate and sensitize meningeal nociceptors, culminating in headaches. The efficacy of relatively blood-brain barrier-impermeable anti-calcitonin gene-related peptide antibodies and triptans in treating migraine attacks, both with and without aura, supports the concept of migraine pain originating in meninges. Additionally, PET studies utilizing inflammation markers have revealed meningeal inflammatory activity in patients experiencing migraine with aura, particularly over the occipital cortex generating visual auras. The parenchymal neuroinflammatory signaling involving neurons, astrocytes, and microglia, which eventually extends to the meninges, can link non-homeostatic perturbations in the insensate brain to pain-sensitive meninges. Recent experimental research has brought deeper insight into parenchymal signaling mechanisms: Neuronal pannexin-1 channels act as stress sensors, initiating the inflammatory signaling by inflammasome formation and high-mobility group box-1 release in response to transient perturbations such as cortical spreading depolarization (CSD) or synaptic metabolic insufficiency caused by transcriptional changes induced by migraine triggers like sleep deprivation and stress. After a single CSD, astrocytes respond by upregulating the transcription of proinflammatory enzymes and mediators, while microglia are involved in restoring neuronal structural integrity; however, repeated CSDs may prompt microglia to adopt a pro-inflammatory state. Transcriptional changes from pro- to anti-inflammatory within 24 h may serve to dampen the inflammatory signaling. The extensive coverage of brain surface and perivascular areas by astrocyte endfeet suggests their role as an interface for transporting inflammatory mediators to the cerebrospinal fluid to contribute to meningeal nociception.

Conclusion

We propose that neuronal stress induced by CSD or synaptic activity-energy mismatch may initiate a parenchymal inflammatory signaling cascade, transmitted to the meninges, thereby triggering lasting headaches characteristic of migraine, with or without aura. This neuroinflammatory interplay between parenchymal and meningeal cells points to the potential for novel targets for migraine treatment and prophylaxis.
Genetic diversity of United States Rambouillet, Katahdin and Dorper sheep
Authors: Becker Gabrielle M. , Thorne Jacob W. , Burke Joan M. , Lewis Ronald M. , Notter David R. , Morgan James L. M. , Schauer Christopher S. , Stewart Whit C. , Redden R. R. , Murdoch Brenda M.
Published: July 2024

Background

Managing genetic diversity is critically important for maintaining species fitness. Excessive homozygosity caused by the loss of genetic diversity can have detrimental effects on the reproduction and production performance of a breed. Analysis of genetic diversity can facilitate the identification of signatures of selection which may contribute to the specific characteristics regarding the health, production and physical appearance of a breed or population. In this study, breeds with well-characterized traits such as fine wool production (Rambouillet, N = 745), parasite resistance (Katahdin, N = 581) and environmental hardiness (Dorper, N = 265) were evaluated for inbreeding, effective population size (Ne), runs of homozygosity (ROH) and Wright’s fixation index (FST) outlier approach to identify differential signatures of selection at 36,113 autosomal single nucleotide polymorphisms (SNPs).

Results

Katahdin sheep had the largest current Ne at the most recent generation estimated with both the GONe and NeEstimator software. The most highly conserved ROH Island was identified in Rambouillet with a signature of selection on chromosome 6 containing 202 SNPs called in an ROH in 50 to 94% of the individuals. This region contained the DCAF16, LCORL and NCAPG genes that have been previously reported to be under selection and have biological roles related to milk production and growth traits. The outlier regions identified through the FST comparisons of Katahdin with Rambouillet and Dorper contained genes with known roles in milk production and mastitis resistance or susceptibility, and the FST comparisons of Rambouillet with Katahdin and Dorper identified genes related to wool growth, suggesting these traits have been under natural or artificial selection pressure in these populations. Genes involved in the cytokine-cytokine receptor interaction pathways were identified in all FST breed comparisons, which indicates the presence of allelic diversity between these breeds in genomic regions controlling cytokine signaling mechanisms.

Conclusions

In this paper, we describe signatures of selection within diverse and economically important U.S. sheep breeds. The genes contained within these signatures are proposed for further study to understand their relevance to biological traits and improve understanding of breed diversity.
Comparing methylation levels assayed in GC-rich regions with current and emerging methods
Authors: Guanzon Dominic , Ross Jason P , Ma Chenkai , Berry Oliver , Liew Yi Jin
Published: July 2024

DNA methylation is an epigenetic mechanism that regulates gene expression, and for mammals typically occurs on cytosines within CpG dinucleotides. A significant challenge for methylation detection methods is accurately measuring methylation levels within GC-rich regions such as gene promoters, as inaccuracies compromise downstream biological interpretation of the data. To address this challenge, we compared methylation levels assayed using four different Methods Enzymatic Methyl-seq (EM-seq), whole genome bisulphite sequencing (WGBS), Infinium arrays (Illumina MethylationEPIC, “EPIC”), and Oxford Nanopore Technologies nanopore sequencing (ONT) applied to human DNA. Overall, all methods produced comparable and consistent methylation readouts across the human genome. The flexibility offered by current gold standard WGBS in interrogating genome-wide cytosines is surpassed technically by both EM-seq and ONT, as their coverages and methylation readouts are less prone to GC bias. These advantages are tempered by increased laboratory time (EM-seq) and higher complexity (ONT). We further assess the strengths and weaknesses of each method, and provide recommendations in choosing the most appropriate methylation method for specific scientific questions or translational needs.
Bacillus anthracis in South Africa, 1975–2013: are some lineages vanishing?
Authors: Lekota Kgaugelo Edward , Hassim Ayesha , Ledwaba Maphuti Betty , Glover Barbara A. , Dekker Edgar. H. , van Schalkwyk Louis Ockert , Rossouw Jennifer , Beyer Wolfgang , Vergnaud Gilles , van Heerden Henriette
Published: July 2024

The anthrax-causing bacterium Bacillus anthracis comprises the genetic clades A, B, and C. In the northernmost part (Pafuri) of Kruger National Park (KNP), South Africa, both the common A and rare B strains clades occur. The B clade strains were reported to be dominant in Pafuri before 1991, while A clade strains occurred towards the central parts of KNP. The prevalence of B clade strains is currently much lower as only A clade strains have been isolated from 1992 onwards in KNP. In this study 319 B. anthracis strains were characterized with 31-loci multiple-locus variable-number tandem repeat analysis (MLVA-31). B clade strains from soil (n = 9) and a Tragelaphus strepsiceros carcass (n = 1) were further characterised by whole genome sequencing and compared to publicly available genomes. The KNP strains clustered in the B clade before 1991 into two dominant genotypes. South African strains cluster into a dominant genotype A.Br.005/006 consisting of KNP as well as the other anthrax endemic region, Northern Cape Province (NCP), South Africa. A few A.Br.001/002 strains from both endemic areas were also identified. Subclade A.Br.101 belonging to the A.Br.Aust94 lineage was reported in the NCP. The B-clade strains seems to be vanishing, while outbreaks in South Africa are caused mainly by the A.Br.005/006 genotypes as well as a few minor clades such as A.Br.001/002 and A.Br.101 present in NCP. This work confirmed the existence of the rare and vanishing B-clade strains that group in B.Br.001 branch with KrugerB and A0991 KNP strains.
Genome-wide association studies of body size traits in Tibetan sheep
Authors: Liu Dehui , Li Xue , Wang Lei , Pei Quanbang , Zhao Jincai , Sun De , Ren Qianben , Tian Dehong , Han Buying , Jiang Hanjing , Zhang Wenkui , Wang Song , Tian Fei , Liu Sijia , Zhao Kai
Published: July 2024

Background

Elucidating the genetic variation underlying phenotypic diversity will facilitate improving production performance in livestock species. The Tibetan sheep breed in China holds significant historical importance, serving as a fundamental pillar of Qinghai’s animal husbandry sector. The Plateau-type Tibetan sheep, comprising 90% of the province’s population, are characterized by their tall stature and serve as the primary breed among Tibetan sheep. In contrast, Zhashijia sheep exhibit larger size and superior meat quality. These two species provide an excellent model for elucidating the genetic basis of body size variation. Therefore, this study aims to conduct a comprehensive genome-wide association study on these two Tibetan sheep breeds to identify single nucleotide polymorphism loci and regulatory genes that influence body size traits in Tibetan sheep.

Result

In this study, the phenotypic traits of body weight, body length, body height, chest circumference, chest depth, chest width, waist angle width, and pipe circumference were evaluated in two Tibetan sheep breeds: Plateau-type sheep and Zhashijia Tibetan sheep. Whole genome sequencing generated 48,215,130 high-quality SNPs for genome-wide association study. Four methods were applied and identified 623 SNPs significantly associated with body size traits. The significantly associated single nucleotide polymorphisms identified in this study are located near or within 111 candidate genes. These genes exhibit enrichment in the cAMP and Rap1 signaling pathways, significantly affecting animal growth, and body size. Specifically, the following genes were associated: ASAP1, CDK6, FRYL, NAV2, PTPRM, GPC6, PTPRG, KANK1, NTRK2 and ADCY8.

Conclusion

By genome-wide association study, we identified 16 SNPs and 10 candidate genes associated with body size traits in Tibetan sheep, which hold potential for application in genomic selection breeding programs in sheep. Identifying these candidate genes will establish a solid foundation for applying molecular marker-assisted selection in sheep breeding and improve our understanding of body size control in farmed animals.
Transcriptome and weighted gene co-expression network analyses reveal key genes and pathways involved in early fruit ripening in Citrus sinensis
Authors: Chen Jianmei , Xie Lihong , Lin Yi , Zhong Balian , Wan Shubei
Published: July 2024

Background

The fruit ripening period is an important target trait in fruit tree crop breeding programs. Thus, citrus tree breeders seek to develop extreme early ripening cultivars that allow optimization of citrus maturation periods. In this study, we explored the regulatory network involved in fruit ripening in Citrus sinensis using the ‘Newhall’ navel orange variety and its early-ripening mutant, ‘Gannanzao’. This research will provide a basis for further research on important signaling pathways, gene functions and variety breeding of Citrus sinensis related to fruit ripening period.

Results

Physiological analyses suggested that early fruit ripening in ‘Gannanzao’ is regulated by early accumulation of abscisic acid (ABA), persistently high levels of jasmonic acid (JA), and higher sucrose content in the pericarp. Pericarp samples from ‘Gannanzao’ and ‘Newhall’ navel oranges were sampled for RNA sequencing analysis at 180, 200, and 220 days after flowering; 1430 differentially expressed genes (DEGs) were identified. Functional enrichment analysis indicated that these DEGs were mainly enriched in the plant hormone signal transduction and sugar metabolism pathways, as well as other pathways related to fruit ripening. Important DEGs associated with fruit ripening in ‘Gannanzao’ included genes involved in ABA and JA metabolism and signal transduction, as well as sugar metabolism. Weighted gene co-expression network analysis showed that the deep pink module had the strongest correlations with ABA content, JA content, and early ripening. Based on gene functionality and gene expression analyses of 37 genes in this module, two candidate hub genes and two ethylene response factor 13 (ERF13) genes (Cs_ont_5g000690 and Cs_ont_5g000700) were identified as key genes regulated by ABA and JA signaling. These findings will help to clarify the mechanisms that underlie early citrus fruit ripening and will lead to the development of excellent genetic resources for further breeding of extreme early-ripening varieties.

Conclusions

Through analyses of the ‘Newhall’ navel orange cultivar and its early-ripening mutant ‘Gannanzao’, we identified genes involved in ABA and JA metabolism, signal transduction, and sugar metabolism that were related to fruit ripening. Among these, two ERF13 genes were inferred to be key genes in the regulation of fruit ripening. These findings provide insights into the genetic architecture related to early fruit ripening in C. sinensis.
Integrated analysis of transcriptomics and defense-related phytohormones to discover hub genes conferring maize Gibberella ear rot caused by Fusarium Graminearum
Authors: Yuan Guangsheng , Shi Jiahao , Zeng Cheng , Shi Haoya , Yang Yong , Zhang Chuntian , Ma Tieli , Wu Mengyang , Jia Zheyi , Du Juan , Zou Chaoying , Ma Langlang , Pan Guangtang , Shen Yaou
Published: July 2024

Background

Gibberella ear rot (GER) is one of the most devastating diseases in maize growing areas, which directly reduces grain yield and quality. However, the underlying defense response of maize to pathogens infection is largely unknown.

Results

To gain a comprehensive understanding of the defense response in GER resistance, two contrasting inbred lines ‘Nov-82’ and ‘H10’ were used to explore transcriptomic profiles and defense-related phytohormonal alterations during Fusarium graminearum infection. Transcriptomic analysis revealed 4,417 and 4,313 differentially expressed genes (DEGs) from the Nov-82 and H10, respectively, and 647 common DEGs between the two lines. More DEGs were obviously enriched in phenylpropanoid biosynthesis, secondary metabolites biosynthesis, metabolic process and defense-related pathways. In addition, the concentration of the defense-related phytohormones, jasmonates (JAs) and salicylates (SAs), was greatly induced after the pathogen infection. The level of JAs in H10 was more higher than in Nov-82, whereas an opposite pattern for the SA between the both lines. Integrated analysis of the DEGs and the phytohormones revealed five vital modules based on co-expression network analysis according to their correlation. A total of 12 hub genes encoding fatty acid desaturase, subtilisin-like protease, ethylene-responsive transcription factor, 1-aminocyclopropane-1-carboxylate oxidase, and sugar transport protein were captured from the key modules, indicating that these genes might play unique roles in response to pathogen infection,

Conclusions

Overall, our results indicate that large number DEGs related to plant disease resistance and different alteration of defensive phytohormones were activated during F. graminearum infection, providing new insight into the defense response against pathogen invasion, in addition to the identified hub genes that can be further investigated for enhancing maize GER resistance.
Efficacy of azasetron on postoperative chronic pain after pulmonary surgery: a randomized triple-blind controlled trial
Authors: Xu Yang , Jiang Fei , Shi Shengnan , Zheng Hongyu , Li Xuhong , Ye Xihong , Gong Xingrui
Published: July 2024

Background

Inhibition of 5-HT3 (5-Hydroxyl Tryptamine) receptors is known to enhance morphine analgesia in animal models. We tested the efficacy of azasetron, a 5-HT3 receptor antagonist, on postoperative chronic pain after pulmonary surgery in a randomized triple-blind controlled study.

Methods

A total of 250 patients who were scheduled to receive pulmonary surgery were randomized to patient-controlled analgesia (PCA) using 200 µg sufentanil with normal saline or 200 µg sufentanil with 20 mg azasetron. The numerical rating scale of pain (NRS) was recorded at baseline, postoperative day (POD) 1, 2, 3, 90, and 180. Negative binomial regression was used to identify associated factors for postoperative NRS six months after surgery.

Results

The results showed that azasetron did not affect the primary outcomes: the incidence of postoperative chronic pain on POD90 and 180. However, azasetron decreased postoperative NRS at rest and activity on POD1, 2, and 3. Furthermore, azasetron decreased postoperative nausea and vomiting on POD1 and 2. Univariate and multivariate negative binomial regression analysis identified preoperative pain, smoking, drinking and open surgery are risk factors of chronic pain six months after surgery.

Conclusions

Azasetron did not affect the incidence of chronic pain after pulmonary surgery. The presence of preoperative pain, smoking, drinking, and open surgery were found to be associated with chronic pain six months after surgery.

Clinical trial registration

The trial was registered prior to patient enrollment at the Chinese Clinical Trial Registry (ChiCTR2200060139), 20/05/2022; the site url ishttps://www.chictr.org.cn/.
The individual and combined impacts of pre-existing diabetes and dementia on ischemic stroke outcomes: a registry-based cohort study
Authors: Kyaw Kyi Lae Shune , Pana Tiberiu A. , Bettencourt-Silva Joao H. , Metcalf Anthony K. , Myint Phyo K. , Potter John F.
Published: July 2024

Background

Individually, diabetes mellitus and dementia are associated with poorer outcomes after stroke. However, the combined impact of these pre-existing factors on acute ischemic stroke (AIS) outcomes has not been examined.

Methods

All consecutive patients with AIS admitted to Norfolk and Norwich University Hospitals between 2003 and 2016 (catchment population ~ 900,000) were divided into four groups: those with neither diabetes nor dementia (reference), with diabetes without dementia, with dementia without diabetes, and with both co-morbidities. In-hospital mortality, length of hospital stay (LoS), and disability outcomes were analysed using logistic regressions. Post-discharge mortality and recurrence were assessed using Cox regressions. Additionally, interaction terms were added to the models for the short-term outcomes and long-term mortality to test for synergistic effects of diabetes and dementia. Models were adjusted for age, sex, Oxfordshire Community Stroke Project classification, comorbidities, hematological and biochemical measures, and antithrombotic medications.

Results

The cohort was 10,812 patients with 52% females and a median age of 80. The median follow-up was 3.8 years for stroke recurrence and 5.5 years for mortality. No significant differences between the four groups existed for in-hospital mortality and post-stroke disability. Patients with dementia had significantly longer LoS (OR 2.25 [95% CI: 1.34–3.77] and 1.31 [1.02–1.68] with and without diabetes, respectively). Patients with both comorbidities had the highest risk of stroke recurrence (HR 2.06 [1.12–3.77]), followed by those with only dementia (1.59 [1.15–2.20]) and only diabetes (1.25 [1.06–1.49]). Similarly, the patient group with both diabetes and dementia had the highest long-term mortality risk (1.76 [1.33–2.37]). The hazard ratios for patients with only dementia and only diabetes were 1.71 [1.46–2.01] and 1.19 [1.08–1.32], respectively. No significant interactions were seen between diabetes and dementia with regards to their effects on the outcomes.

Conclusion

Individual and cumulative impacts of the two conditions on long-term mortality and stroke recurrence were notable. However, no synergistic impact of the two comorbidities were seen on the stroke outcomes tested in our study. Therefore, tailoring the management of stroke patients based on additional requirements associated with each pre-existing condition will be more impactful towards improving outcomes.
MicroRNA-19a-3p inhibits endothelial dysfunction in atherosclerosis by targeting JCAD
Authors: Luo Jinque , Wang Ling , Cui Chaoyue , Chen Hongyu , Zeng Wanli , Li Xin
Published: July 2024

Objective

To examine the influences and mechanisms of MicroRNA-19a-3p (miR-19a-3p) on endothelial dysfunction in atherosclerosis.

Methods

An analysis of miR-19a expression was carried out using the Gene Expression Omnibus (GEO) database. The effect of miR-19a-3p on endothelial function in HUVECs was evaluated by miR-19a-3p overexpression under TNF-α treatment. Luciferase assays were performed to explore the potential target genes. Overexpression of junctional protein associated with coronary artery disease (JCAD) was used to examine the effects of miR-19a-3p on cell adhesion, and proliferation.

Results

MiR-19a-3p expression in endothelial cells decreased after exposure to TNF-α and/or oscillatory flow, consistent with the expression change of miR-19a-3p found in atherosclerotic plaques. Additionally, endothelial cell dysfunction and inflammation were significantly diminished by miR-19a-3p overexpression but markedly exacerbated by miR-19a-3p inhibition. MiR-19a-3p transfection significantly decreased the expression of JCAD by binding to the 3’-UTR of JCAD mRNA. Furthermore, the protective effect of miR-19a-3p against endothelial cell dysfunction and inflammation was achieved by regulating JCAD and was closely linked to the Hippo/YAP signaling pathway.

Conclusion

MiR-19a-3p expression is a crucial molecular switch in the onset of atherosclerosis and miR-19a-3p overexpression is a possible pharmacological therapeutic strategy for reversing the development of atherosclerosis.
Accelerating evidence synthesis for safety assessment through ClinicalTrials.gov platform: a feasibility study
Authors: Yu Tianqi , Yang Xi , Clark Justin , Lin Lifeng , Furuya-Kanamori Luis , Xu Chang
Published: July 2024

Background

Standard systematic review can be labor-intensive and time-consuming meaning that it can be difficult to provide timely evidence when there is an urgent public health emergency such as a pandemic. The ClinicalTrials.gov provides a promising way to accelerate evidence production.

Methods

We conducted a search on PubMed to gather systematic reviews containing a minimum of 5 studies focused on safety aspects derived from randomized controlled trials (RCTs) of pharmacological interventions, aiming to establish a real-world dataset. The registration information of each trial from eligible reviews was further collected and verified. The meta-analytic data were then re-analyzed by using 1) the full meta-analytic data with all trials and 2) emulated rapid data with trials that had been registered and posted results on ClinicalTrials.gov, under the same synthesis methods. The effect estimates of the full meta-analysis and rapid meta-analysis were then compared.

Results

The real-world dataset comprises 558 meta-analyses. Among them, 56 (10.0%) meta-analyses included RCTs that were not registered in ClinicalTrials.gov. For the remaining 502 meta-analyses, the median percentage of RCTs registered within each meta-analysis is 70.1% (interquartile range: 33.3% to 88.9%). Under a 20% bias threshold, rapid meta-analyses conducted through ClinicalTrials.gov achieved accurate point estimates ranging from 77.4% (using the MH model) to 83.1% (using the GLMM model); 91.0% to 95.3% of these analyses accurately predicted the direction of effects.

Conclusions

Utilizing the ClinicalTrials.gov platform for safety assessment with a minimum of 5 RCTs holds significant potential for accelerating evidence synthesis to support urgent decision-making.
Pathological complete response after conversion therapy in unresectable hepatocellular carcinoma: a retrospective study
Authors: Jia Junjun , Ding Chenyuan , Mao Mengjie , Gao Feng , Shao Zhou , Zhang Min , Zheng Shusen
Published: July 2024

Background

Hepatocellular carcinoma is a highly lethal tumor worldwide, and China has a correspondingly high incidence and mortality rate. For patients with unresectable hepatocellular carcinoma, the prognosis is often poor. The objective of this retrospective study was to investigate the effects of conversion therapies on these patients.

Methods

The study included patients between the ages of 18 and 75 who were initially diagnosed with unresectable hepatocellular carcinoma and received conversion therapy. After completing surgery, the patients underwent pathological diagnosis, which showed complete necrosis. The study was conducted retrospectively at the First Affiliated Hospital, Zhejiang University School of Medicine, from January 2019 to December 2021. The main objectives of the study were to evaluate the overall survival and recurrence-free survival.

Results

A total of 60 patients who met the inclusion criteria were enrolled. The median age of the patients was 56.6 ± 9.5 years, and 85% of them were male. The one-year overall survival rate (OS) was 98.3%, and the three-year OS was 95.6%. The one-year recurrence-free survival rate (RFS) was 81.1%, and the three-year RFS was 71.4%. In subgroup analysis, there was no statistically significant difference in RFS between patients with BCLC stages 0-A and BCLC stages B-C (p = 0.296). Additionally, there was no statistically significant difference in RFS between patients who received postoperative new adjuvant therapy and those who did not (p = 0.324).

Conclusions

Conversion therapy followed by surgical resection could be a promising treatment for patients with initially unresectable hepatocellular carcinoma, and the prognosis is good with a pathological complete response.
Unveiling clinicopathologic features and outcomes for endoscopic submucosal dissection of early gastric cancer at gastric angulus in China
Authors: Wu Qiaoyan , Li Tongyu , Cui Yangyang , Jiang Haizhong , Fu Yangbo , Jiang Qi , Ding Xiaoyun
Published: July 2024

Background

With advances in endoscopic submucosal dissection (ESD) technique, an increasing number of the Chinese population are being diagnosed with early gastric cancers (EGCs) at gastric angulus. However, the relationship between gastric angulus and EGCs remains obscure.

Objectives

We aimed to unveil the unreported location characteristics of gastric angulus in Chinese EGC patients and the correlation between the degree of submucosal fibrosis and ESD outcomes.

Methods

We retrospectively reviewed the medical records of EGC patients treated with ESD from January 2010 to March 2023. We retrospectively investigated and analyzed 740 EGC patients using multiple analyses.

Results

Following gastric antrum (53.1%), the gastric angulus (21.8%) emerged as the second-most prevalent site for EGCs. It had highest incidence of severe submucosal fibrosis and ulceration than the other parts. Multivariate analysis showed independent associations of submucosal fibrosis at the angulus with ulceration (OR: 3.714, 95% CI: 1.041–13.249), procedure duration (OR: 1.037, 95% CI: 1.014–1.061), and perforation complication (OR: 14.611, 95% CI: 1.626-131.277) (all P < 0.05).

Conclusions

The gastric angulus demonstrates the highest incidence of severe submucosal fibrosis and ulceration for EGCs identified by ESD. This condition is linked to unfavorable outcomes, typically increased perforation risks and prolonged operation duration. Therefore, meticulous dissection is crucial for patients with EGCs in the gastric angulus.
Clinical and radiological effects of Bevacizumab for the treatment of radionecrosis after stereotactic brain radiotherapy
Authors: Zoto Mustafayev Teuta , Turna Menekse , Bolukbasi Yasemin , Tezcanli Evrim , Guney Yildiz , Dincbas Fazilet Oner , Atasoy Beste Melek , Ugurluer Gamze , Caglar Hale Basak , Atalar Banu , Ozyar Enis
Published: July 2024

Purpose

The purpose of this multicenter retrospective study was to analyze the clinical and radiological effects of bevacizumab (BV) on radionecrosis (RN) that developed after stereotactic radiotherapy (SRT) for brain metastasis.

Methods

Forty patients with SRT related symptomatic brain RN treated in 10 radiation oncology centers were analyzed. The clinical response to BV treatment was categorized as follows: complete (no additional treatment required), partial (requiring either steroids or repeat BV), and unresponsive (requiring surgery). The radiological features of brain RN were analyzed in 10 patients whose serial MRI scans were available after corticosteroid and BV treatments.

Results

BV was used as a first line treatment in 11 (27.5%) and as a second line treatment in 29 (72.5%) of patients. The neurological symptoms regressed in 77.5% of patients after treatment with BV (45% complete response, 32.5% partial response). The median edema volume increased from 75.9 cc (range: 5.9-125.8 cc) at RN to 113.65 cc (range: 1.5-382.1 cc) after use of corticosteroids, representing a rate of 39.8% increase (p = 0.074). However, after BV treatment the median volume of edema decreased to 19.5 cc (range: 0-163.3 cc) which represents a difference of 62.2% (p = 0.041) from RN.

Conclusion

The use of BV caused clinical response rate of 77.5% and a good radiological response in corticosteroid unresponsive patients. The role of BV should be further investigated in prospective studies.
Impacts of COVID-19 shelter in place across key life domains among immigrant farmworker Latina mothers and young adults
Authors: Bakal Michael , Ambriz Elizabeth , Ortiz-Pivaral Lizbeth , Kogut Katherine , Rood Claire Snell , Rauch Stephen , Eskenazi Brenda , Deardorff Julianna
Published: July 2024

Objective

Individuals and families from racial and ethnic groups experience social and economic disadvantage making them vulnerable to the disproportionate impact of the COVID-19 pandemic. This study sought to capture the impacts of Shelter in Place (SIP) across key life domains including family life, education, work, mental health, and coping strategies among a sample of Mexican-origin mothers who were currently engaged in agricultural work, or whose spouses were engaged in agricultural work, and young adults who had a parent working in agriculture.

Method

During the summer of 2020, while California was under SIP orders, we conducted three virtual focus groups using Zoom(r). We recruited focus group participants from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), an ongoing, 20-year, longitudinal cohort study of Mexican-origin families in a predominantly agricultural area of California. Three focus groups were conducted with mothers (n = 9), mean age = 48 years, young adult women (n = 8) and young adult men (n = 5), mean age = 18 years, respectively.

Results

Mothers reported high levels of stress stemming from fear of Covid-19 infection, work instability and financial concerns, children’s schooling, anxiety about an uncertain future, and the demands of caretaking for dependents. Adverse mental health impacts were particularly pronounced among participants experiencing multiple adversities pre-dating the pandemic, including unemployment, single motherhood, and having undocumented family members. For young adults, work instability and varying work hours were also a source of stress because they made it difficult to make decisions about the future, such as whether to attend college or how many classes to take. Families used coping strategies including expressing gratitude, focusing on what’s under one’s control, familismo, and community engagement to manage mental health challenges during SIP.

Conclusion

In the event of future pandemics or disasters, particular attention is needed to those who experience unemployment, are undocumented and/or have undocumented family members, and/or are single parents facing economic adversity. During public health emergencies, action at the local, state, and national level is needed to support farmworkers and other vulnerable groups’ secondary major stressors stemming from inequities in access to affordable housing, childcare, living wages, healthcare, and other benefits.
Association between metabolic dysfunction-associated steatotic liver disease and pulmonary function: a population-based and two-sample mendelian randomization study
Authors: Feng Ting , Li Jiaming , Wu Lihao , He Xingxiang , Ye Junzhao
Published: July 2024

Background

Hepatic steatosis and its related complications are risk factors for multiple respiratory diseases; however, the causal relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and pulmonary function remains controversial. We aimed to identify it using a national cohort and Mendelian randomization (MR).

Methods

We enrolled 30,442 participants from the 2007 to 2012 National Health and Nutrition Examination Survey. Demographics, pulmonary function indices (forced expiratory volume in 1 s [FEV1], forced vital capacity [FVC]), and variables used to calculate the liver fat score (LFS) were collected. A two-sample MR analysis employing the summary data of genome-wide association studies on MASLD and FEV1/FVC, chronic obstructive pulmonary disease (COPD), and asthma from the Finngen Biobank and Medical Research Council Integrative Epidemiology Unit was performed.

Results

A total of 3,462 participants, 1,335 of whom had MASLD (LFS > -0.640), were finally included in the study. The FEV1 (3,204.7 vs. 3,262.5 ml, P = 0.061), FVC (4,089.1 vs. 4,143.8 ml, P = 0.146), FEV1/FVC ratio (78.5% vs. 78.8%, P = 0.233), and FEV1/predicted FEV1 ratio (146.5% vs. 141.7%, P = 0.366) were not significantly different between people with MASLD and those without. Additionally, the MR analysis suggested no causal correlation between MASLD and FEV1/FVC (P = 0.817), MASLD and COPD (P = 0.407), and MASLD and asthma (P = 0.808). Reverse MR studies showed no causal relationships yet (all P > 0.05).

Conclusion

Our study provides convincing evidence that there is no causal association between MASLD and pulmonary function.
Effect of Biomin F toothpaste and Diode laser on remineralization of white spot lesions (in vitro study)
Authors: Eldeeb Amira I. , Tamish Nazla O. , Madian Ahmed M.
Published: July 2024

Background

White-spot lesions are considered an initial carious stage characterized by an outer enamel layer with significantly reduced mineralization. This study was conducted to assess the combined effect of Biomin F toothpaste and Diode laser on remineralization of white spot lesions.

Materials and methods

An invitro study conducted on a total of 30 premolars divided into three groups; Group A (Biomin F Tooth paste), Group B (Biomin F with laser application for 30 sec), Group C (Negative control). The three groups were submitted to three stages; stage 1:Baseline,stage 2:After demineralization ,and stage 3:After remineralization. In each stage, elemental analysis(calcium, phosphorus, and fluoride)was measured quantitatively using Energy Dispersive X-ray (EDX) analysis and qualitatively by micrographs using scanning electron microscope. The data were tested to find significant difference between mineral changes during stages by using (ANOVA) test and Bonferroni test.

Results

Calcium, phosphorus and fluoride ions decreased in all groups after demineralization. In stage 3, after application of remineralizing agents, Calcium ions increased significantly in groups A and B where p<.05. As regards to the phosphorus ions, a significant increase was observed in all groups with group A showed the highest gain as phosphorus level percentage change (%mass) was 56.52±18.02 . Fluoride ions increased significantly in groups A and B (p<0.05) but decreased significantly in group C. There was no statistical significant difference between group A and B (p ≥.05) in calcium, phosphorus, and fluoride level after remineralization.

Conclusion

Within the limitation of the present study, we concluded that Biomin F toothpaste is promising in the repairing of white spot lesions on the surface of the demineralized enamel. Diode laser did not affect the remineralizing ability of Biomin F toothpaste.
Transforming healthcare: A pilot study to improve primary healthcare professionals’ self-management support behaviour through blended learning
Authors: Timmermans Lotte , Decat Peter , Foulon Veerle , Van Hecke Ann , Vermandere Mieke , Schoenmakers Birgitte ,   the Primary Care Academy
Published: July 2024

Background

Self-management of a chronic condition is a complex but increasingly important issue. However, a supportive attitude and behaviour among healthcare professionals is hampered by a lack of awareness, knowledge and motivation. In addition, the role of professionals in supporting self-management seems unclear.

Methods

A blended learning program for primary healthcare professionals was developed to strengthen self-management support in primary care. The program was piloted in community health centres and multidisciplinary medical practices in Flanders. Using the Kirkpatrick model, the impact on healthcare professionals’ reaction, learning and behaviour regarding self-management support was evaluated.

Results

A total of 60 healthcare professionals registered for the educational program. Post-learning questionnaires and verbal feedback showed a positive response, with professionals highly appreciating the innovative blended learning approach. In terms of learning, participants showed a good understanding of self-management support, although nuances were observed in the application of acquired knowledge to practice scenarios. Finally, preliminary insights into behavioural change were explored, revealing a positive impact of the intervention on participants’ supportive self-management behaviours in healthcare practice.

Conclusions

Our study provides preliminary insights into the outcomes of a blended learning program designed to increase awareness and knowledge of self-management support among professionals. The program needs to be refined for general implementation in primary care.
Using a novel methodology to map Post-COVID services for children and young people in England: a web-based systematic search
Authors: Newlands Fiona , Fox-Smith Lana , Balakrishnan Sonia , Lord Gareth , Chalder Trudie , Dalrymple Emma , Ford Tamsin , Harnden Anthony , Heyman Isobel , Ladhani Shamez N , Pereira Snehal M Pinto , Segal Terry Y , Stephenson Terence , Whittaker Elizabeth , Shafran Roz
Published: July 2024

Background

Post-COVID Condition (PCC), also known as ‘Long COVID,’ refers to persistent symptoms following a coronavirus 2 (SARS-CoV-2) infection. The prevalence of PCC in children and adolescents varies, impacting multiple body systems and affecting daily functioning. Specialised paediatric hubs were established in England to address the needs of young individuals with PCC. Additional local services also emerged, yet patients report challenges accessing services. To better understand the landscape of paediatric PCC services, we used a novel methodology using a web-based systematic search.

Methods

A web-based search was conducted in July 2023 using DEVONagent Pro. Search terms related to Long COVID and Pediatrics in England. Eligible sources providing information on PCC services for children and young people were included. A supplementary manual search and NHS England Post-COVID Network were also consulted. Data extraction included service location, characteristics, and referral pathways. Population estimates were derived from UK Census data.

Results

Among 342 identified records, 27 services met eligibility criteria, distributed unevenly across regions. Specialised hubs covered 13 locations, while additional services were concentrated in the South of England and London. Services varied in team composition, age range treated, and support offered. A lack of standardised approaches for paediatric PCC was evident.

Discussion

We used a novel methodology for systematically mapping online resources, providing valuable insights into service accessibility and aiding the identification of potential gaps. We observed geographical disparities in access to paediatric PCC services and the absence of standardised approaches in managing symptoms. Given the challenges faced by young individuals seeking support for their PCC the need for equitable and standardised care became apparent. The study contributes to closing the research-practice gap and calls for further research to identify effective treatments for paediatric PCC, acknowledging the diversity of reported symptoms and the importance of tailored approaches.
Visualizing cancer resistance via nano-quenching and recovery detector of CD44
Authors: Zeng Jialin , Yang Lihua , Zeng Lingke , Feng Chengyu , Yang Yuepeng , Ye Yingying , Zhang Wenxin , He Jian , Zhang Chao
Published: July 2024

Drug resistance to chemotherapy in cancers remains significant clinical challenges. CD44 modulates cellular adhesion, migration and growth, which plays a pivotal role in driving cancer resistance and even recurrence. Despite ongoing efforts, accurate, safe, and real-time dynamic monitoring techniques for CD44 expression remain inadequate in guiding the management of drug-resistant cancer treatment. In this study, we developed a nano-quenching and recovery detector of CD44 (Cy3-AptCD44@BPNSs) for visualizing cancer drug resistance. The fluorescence recovery of the detector is directly related to the CD44 expression level on cancer cells, which can be used to indicate the degree of drug resistance. It’s confirmed that downregulating CD44 expression on cancer cells results in a corresponding decrease in the fluorescence intensity of the detector, which enables precise and dynamic monitoring of CD44. In addition, the Cy3-AptCD44@BPNSs also exhibited specificity in detecting CD44. This visualizing strategy may open up a wide range of possibilities for rapid recognition to cancer drug resistance, which is more efficient and flexible.