bluuebunny/crossref_metadata_2025 huggingface dataset:
The Minhang Pediatric Biobank cohort study: protocol overview and baseline characteristics
Authors: Wen Xiaosa , Zhang Xinyue , Qiu Yun , Wang Yaqin , Zhu Liujie , Liu Tao , Ruan Zengliang
Published: April 2024

Background

Little has been done to establish biobanks for studying the environment and lifestyle risk factors for diseases among the school-age children. The Minhang Pediatric Biobank (MPB) cohort study aims to identify factors associated with health and diseases of school-aged children living in the urban or suburban area of Shanghai.

Methods

This population-based cohort study was started in all sub-districts/towns of Minhang district of Shanghai in 2014. First-grade students in elementary school were enrolled during the time of their routine physical examinations, with self-administered questionnaires completed by their primary caregivers. Additional information was extracted from multiple health information systems. Urine and saliva samples were collected during the baseline survey and follow-up visits.

Results

At the end of 2014 academic year, a total number of 8412 children and their parents were recruited, including 4339 boys and 4073 girls. All the participants completed the baseline survey and physical examination, and 7128 urine and 2767 saliva samples were collected. The five most prevalent childhood diseases in this population were dental caries, bronchitis, pneumonia, asthma and overweight/obese.

Conclusions

The MPB cohort has been successfully established, serving as a useful platform for future research relating to the genetic, environmental and lifestyle risk factors for childhood diseases.
Semaphorin 7A promotes endothelial permeability and inflammation via plexin C1 and integrin β1 in Kawasaki disease
Authors: Huang Junhua , Zhao Chuanmei , Zhang Shuwan
Published: April 2024

Background

Kawasaki disease (KD) is a pediatric systemic vasculitis characterized by endothelial cell dysfunction. Semaphorin 7A (Sema7A) has been reported to regulate endothelial phenotypes associated with cardiovascular diseases, while its role in KD remains unknown. This study aims to investigate the effect of Sema7A on endothelial permeability and inflammatory response in KD conditions.

Methods

Blood samples were collected from 68 KD patients and 25 healthy children (HC). The levels of Sema7A and A Disintegrin and Metalloprotease 17 (ADAM17) in serum were measured by enzyme-linked immunosorbent assay (ELISA), and Sema7A expression in blood cells was analyzed by flow cytometry. Ex vivo monocytes were used for Sema7A shedding assays. In vitro human coronary artery endothelial cells (HCAECs) were cultured in KD sera and stimulated with Sema7A, and TNF-α, IL-1β, IL-6, and IL-18 of HCAECs were measured by ELISA and qRT-PCR. HCAECs monolayer permeability was measured by FITC-dextran.

Results

The serum level of Sema7A was significantly higher in KD patients than in HC and correlated with disease severity. Monocytes were identified as one of the source of elevated serum Sema7A, which implicates a process of ADAM17-dependent shedding. Sera from KD patients induced upregulation of plexin C1 and integrin β1 in HCAECs compared to sera from HC. Sema7A mediated the proinflammatory cytokine production of HCAECs in an integrin β1-dependent manner, while both plexin C1 and integrin β1 contributed to Sema7A-induced HCAEC hyperpermeability.

Conclusions

Sema7A is involved in the progression of KD vasculitis by promoting endothelial permeability and inflammation through a plexin C1 and integrin β1-dependent pathway. Sema7A may serve as a potential biomarker and therapeutic target in the prognosis and treatment of KD.
Mortality burden of cardiovascular disease attributable to ambient PM2.5 exposure in Portugal, 2011 to 2021
Authors: Corda Mariana O. , Charalampous Periklis , Haagsma Juanita A. , Assunção Ricardo , Martins Carla
Published: April 2024

Background

Exposure to high levels of environmental air pollution causes several health outcomes and has been associated with increased mortality, premature mortality, and morbidity. Ambient exposure to PM2.5 is currently considered the leading environmental risk factor globally. A causal relationship between exposure to PM2.5 and the contribution of this exposure to cardiovascular morbidity and mortality was already demonstrated by the American Heart Association.

Methods

To estimate the burden of mortality attributable to environmental risk factors, a comparative risk assessment was performed, considering a “top-down” approach. This approach uses an existing estimate of mortality of the disease endpoint by all causes as a starting point. A population attributable fraction was calculated for the exposure to PM2.5the overall burden of IHD and stroke was multiplied by the PAF to determine the burden attributable to this risk factor. The avoidable burden was calculated using the potential impact fraction (PIF) and considering the WHO-AQG 2021 as an alternative scenario.

Results

Between 2011 and 2021, the ambient exposure to PM2.5 resulted in a total of 288,862.7 IHD YLL and a total of 420,432.3 stroke YLL in Portugal. This study found a decreasing trend in the mortality burden attributable to PM2.5 exposure, for both males and females and different age-groups. For different regions of Portugal, the same trend was observed in the last years. The mortality burden attributable to long-term exposure to PM2.5 was mainly concentrated in Lisbon Metropolitan Area, North and Centre. Changes in the exposure limits to the WHO recommended value of exposure (WHO-AQG 2021) have a reduction in the mortality burden due to IHD and stroke attributable to PM2.5 exposure, in Portugal.

Conclusion

Between 2011 and 2021, approximately 22% and 23% of IHD and stroke deaths were attributable to PM2.5 exposure. Nevertheless, the mortality burden attributable to cardiovascular diseases has been decreasing in last years in Portugal. Our findings provide evidence of the impact of air pollution on human health, which are crucial for decision-making, at the national and regional level.
The effect of retirement on physical and mental health in China: a nonparametric fuzzy regression discontinuity study
Authors: Wang Ting , Liu Huizhen , Zhou Xiaoqin , Wang Changxi
Published: April 2024

Background

With the rapid aging of the domestic population, China has a strong incentive to increase the statutory retirement age. How retirement affects the health of the elderly is crucial to this policymaking. The health consequences of retirement have been debated greatly. This study aims to investigate the effects of retirement on physical and mental health among Chinese elderly people.

Methods

The data we use in this study comes from four waves (2011, 2013, 2015, and 2018) of the Harmonized China Health and Retirement Longitudinal Study (Harmonized CHARLS), a prospective cohort. We use the nonparametric fuzzy regression discontinuity design to estimate the effects of retirement on physical and mental health. We test the robustness of our results with respect to different bandwidths, kernel functions, and polynomial orders. We also explore the heterogeneity across gender and education.

Results

Results show that retirement has an insignificant effect on a series of physical and mental health outcomes, with and without adjusting several sociodemographic variables. Heterogeneity exists regarding gender and education. Although stratified analyses indicate that the transition from working to retirement leaves minimal effects on males and females, the effects go in the opposite direction. This finding holds for low-educated and high-educated groups for health outcomes including depression and cognitive function. Most of the results are stable with respect to different bandwidths, kernel functions, and polynomial orders.

Conclusions

Our results suggest that it is possible to delay the statutory retirement age in China as retirement has insignificant effects on physical and mental health. However, further research is needed to assess the long-term effect of retirement on health.
The learning curve of a novel seven-axis robot-assisted total hip arthroplasty system: a randomized controlled trial
Authors: Sun Haocheng , Lu Hanpeng , Xiao Qiang , Ding Zichuan , Luo Zeyu , Zhou Zongke
Published: April 2024

Bacground

The aim of this study was to assess the learning curve of a novel seven-axis robot-assisted total hip arthroplasty (RaTHA) system.

Methods

A total of 59 patients who underwent unilateral total hip arthroplasty at our institution from June 2022 to September 2022 were prospectively included in the study. In this randomized controlled clinical trial, robot-assisted THA (RaTHA) and Conventional THA (CoTHA) were performed using cumulative sum (CUSUM) analysis to evaluate the learning curve of the RaTHA system. The demographic data, preopera1tive clinical data, duration of operation, postoperative Harris Hip Score (HHS), postoperative Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and duration of operation between the learning stage and the proficiency stage of the RaTHA group were compared between the two groups.

Results

The average duration of operation of the RaTHA group was increased by 34.73 min compared with the CoTHA group (104.26 ± 19.33 vs. 69.53 ± 18.38 min, p < 0.01). The learning curve of the RaTHA system can be divided into learning stage and proficiency stage, and the former consists of the first 13 cases by CUSUM analysis. In the RaTHA group, the duration of operation decreased by 29.75 min in the proficiency stage compared to the learning stage (121.12 ± 12.84 vs.91.37 ± 12.92, p < 0.01).

Conclusions

This study demonstrated that the surgical team required a learning curve of 13 cases to become proficient using the RaTHA system. The duration of operation, total blood loss, and drainage gradually shortened (decreased) with the learning curve stage, and the differences were statistically significant.

Trial registration

Number: ChiCTR2200061630, Date: 29/06/2022.
Feasibility and efficacy of minimally invasive limited resection for primary duodenal gastrointestinal stromal tumors: a retrospective cohort study
Authors: Wu Longhang , Liu Miao , Lin Xianchao , Wang Congfei , Yang Yuanyuan , Fang Haizong , Huang Heguang , Lin Ronggui , Lu Fengchun
Published: April 2024

Background

The primary duodenal gastrointestinal stromal tumor (GIST) is a rare type of gastrointestinal tract tumor. Limited resection (LR) has been increasingly performed for duodenal GIST. However, only a few studies reported minimally invasive limited resection (MI-LR) for primary duodenal GIST.

Methods

The clinical data of 33 patients with primary duodenal GIST from December 2014 to February 2024 were retrospectively analyzed including 23 who received MI-LR and 10 who received laparoscopic or robotic pancreaticoduodenectomy (LPD/RPD).

Results

A total of 33 patients with primary duodenal GIST were enrolled and retrospectively reviewed. Patients received MI-LR exhibited less OT (280 vs. 388.5min, P=0.004), EBL (100 vs. 450ml, P<0.001), and lower morbidity of postoperative complications (52.2% vs. 100%, P=0.013) than LPD/RPD. Patients received LPD/RPD burdened more aggressive tumors with larger size (P=0.047), higher classification (P<0.001), and more mitotic count/50 HPF(P=0.005) compared with patients received MI-LR. The oncological outcomes were similar in MI-LR group and LPD/RPD group.

All the patients underwent MI-LR with no conversion, including 12 cases of LLR and 11 cases of RLR. All of the clinicopathological data of the patients were similar in both groups. The median OT was 280(210-480) min and 257(180-450) min, and the median EBL was 100(20-1000) mL and 100(20-200) mL in the LLR and the RLR group separately. The postoperative complications mainly included DGE (LLR 4 cases, 33.4% and RLR 4 cases, 36.4%), intestinal fistula (LLR 2 cases, 16.7%, and RLR 0 case), gastrointestinal hemorrhage (LLR 0 case and RLR 1 case, 9.1%), and intra-abdominal infection (LLR 3 cases, 25.0% and RLR 1 case, 9.1%). The median postoperative length of hospitalization was 19.5(7-46) days in the LLR group and 19(9-38) days in the RLR group. No anastomotic stenosis, local recurrence or distant metastasis was observed during the follow-up period in the two groups.

Conclusions

Minimally invasive limited resection is an optional treatment for primary duodenal GIST with satisfactory short-term and long-term oncological outcomes.
Outcome assessment methods of bioactive and biodegradable materials as pulpotomy agents in primary and permanent teeth: a scoping review
Authors: Elhamouly Yasmine , Adham May M. , Dowidar Karin M L , El Backly Rania M.
Published: April 2024

Background

Pulpotomy procedures aiming to preserve and regenerate the dentin-pulp complex have recently increased exponentially due to developments in the field of biomaterials and tissue engineering in primary and permanent teeth. Although the number of studies in this domain has increased, there is still scarcity of evidence in the current literature.

Objectives

(1) Report the methods of outcome assessment of pulpotomy clinical trials in both primary and permanent teeth; (2) Identify the various bioactive agents and biodegradable scaffolds used in pulpotomy clinical trials in both primary and permanent teeth.

Materials and methods

A scoping review of the literature was performed, including a search of primary studies on PubMed, Scopus, Web of Science, ProQuest and Clinicaltrials.gov. A search for controlled trials or randomized controlled trials published between 2012 and 2023 involving primary or permanent teeth receiving partial or full pulpotomy procedures using bioactive/regenerative capping materials was performed.

Results

127 studies out of 1038 articles fulfilled all the inclusion criteria and were included in the current scoping review. More than 90% of the studies assessed clinical and radiographic outcomes. Histological, microbiological, or inflammatory outcomes were measured in only 9.4% of all included studies. Majority of the studies (67.7%) involved primary teeth. 119 studies used non-degradable bioactive cements, while biodegradable scaffolds were used by 32 studies, natural derivates and plant extracts studies were used in only 7 studies. Between 2012 (4 studies) and 2023 (11 studies), there was a general increase in the number of articles published. India, Egypt, Turkey, and Iran were found to have the highest total number of articles published (28, 28,16 and 10 respectively).

Conclusions

Pulpotomy studies in both primary and permanent teeth relied mainly on subjective clinical and radiographic outcome assessment methods and seldom analyzed pulpal inflammatory status objectively. The use of biodegradable scaffolds for pulpotomy treatments has been increasing with an apparent global distribution of most of these studies in low- to middle-income countries. However, the development of a set of predictable outcome measures as well as long-term evidence from well conducted clinical trials for novel pulpotomy dressing materials are still required.
Determining the position of the lingula and the mandibular foramen using the antilingula in orthognathic surgery
Authors: Vorakulpipat Chakorn , Arayapisit Tawepong , Topothai Pee , Bhunyanaphakul Vathanai , Tiptimaphan Keerati , Apilakkitakul Nattha , Chantadul Varunya
Published: April 2024

Background

The antilingula located on the lateral surface of the mandibular ramus has been served as a surgical landmark for the mandibular foramen on the medial surface for decades. However, whether the antilingula truly represents the lingula which is the bony prominence overlapping the mandibular foramen, or the foramen itself, is still unclear. This study thus aimed to examine the position of the antilingula in relation to three reference points: the lingula, the anterior and the posterior borders of the mandibular foramen, as well as to the reference plane used in the inferior alveolar nerve block, and to the posterior border of the mandible.

Methods

This observational study was performed in 113 Thai dry mandibles. The antilingula were identified followed by transferring the reference points to the lateral surface. The distances from the antilingula to the reference points, the reference plane and the posterior border of the ramus were then measured. Chi-square test was calculated for side-dependency of the antilingula. Paired t-test was calculated for difference in measurements in left and right sides.

Results

The antilingula could be identified in 92.48% of the mandibles with 86.67 – 90.00% accuracy and 86.67% reliability. There was no significant difference in the presence of the antilingula on left and right sides (p = 0.801). Only 2.5% and 0.83% of the antilingula correspond to the lingula and the anterior border of the mandibular foramen, respectively. However, 85% of the reference points were located within 11 mm radius. The antilingula was found located 2.80 mm inferior to the reference plane and 16.84 mm from the posterior border of the ramus.

Conclusions

The antilingula does not concur with the reference points on the medial surface. Our study also suggests that the safe area for vertical osteotomy is 11 mm posterior to the antilingula or at 30% of the length from the posterior border parallel to the occlusal plane. The use of more accurate techniques in localizing the mandibular foramen combined with the antilingula is more recommended than using the antilingula as a sole surgical guide.
Cancer-related fatigue and activities of daily living: lessons learned from the COVID-19 pandemic
Authors: Urbano Chamorro Iveth , de la Torre-Montero Julio C.
Published: April 2024

Background

Cancer-related fatigue is a prevalent condition in all stages of oncologic disease that is poorly diagnosed, with a negative impact on physical function to perform activities of daily living. Fatigue is also one of the main manifestations in post-COVID-19 syndrome, and few studies have explored the functionality of cancer patients after infection by the new coronavirus. This study was designed to assess cancer-related fatigue symptoms and their implications on physical function and quality of life during the pandemic.

Methodology

An observational study with a cross-sectional survey in cancer patients ≥ 18 years of age was conducted. The Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F), the perception of asthenia and performance status were evaluated, and the differences between groups according to the history of COVID-19 were calculated.

Results

A total of 60 cancer patients had an average age of 33.5 ± 10.11 years, 73.3% were female, and 98.3% had an Eastern Cooperative Oncology Group-Performance Status level < 2. Severe fatigue was found in 43.3% of patients, and the average FACIT-F score was 33.5 ± 10.11. The proportion of coronavirus infection was 13,3%, and the performance of this group was worse on the scale compared to the group without infection (25 ± 10,40 vs. 34,81 ± 9,50 [p = 0,009]). There was a significant correlation between visual analog scale values and FACIT-F scale scores (Pearson’sr= -0.76).

Conclusion

SARS-CoV-2 infection could increase cancer-related fatigue symptoms, limiting activities of daily living and impairing quality of life.
Gynecological health and uptake of gynecological care after domestic or sexual violence: a qualitative study in an emergency shelter
Authors: Iraola Elisabeth , Menard Jean-Pierre , Buresi Isabelle , Chariot Patrick
Published: April 2024

Background

Domestic and sexual violence have been linked to adverse gynecological and obstetric outcomes. Survivors often find it difficult to verbalize such violence due to feelings of shame and guilt. Vulnerable or socially excluded women are frequently excluded from research, particularly qualitative studies on violence. This study aimed to characterize the perceived impact of domestic or sexual violence on the gynecological health and follow-up among women with complex social situations.

Methods

We analyzed the data following inductive thematic analysis methods.

Results

Between April 2022 and January 2023, we conducted 25 semi-structured interviews, lasting on average 90 min (range: 45–180), with women aged between 19 and 52, recruited in an emergency shelter in the Paris area. The women described physical and psychological violence mainly in the domestic sphere, their altered gynecological and mental health and their perception of gynecological care. The levels of uptake of gynecological care were related to the characteristics of the violence and their consequences. The description of gynecological examination was close to the description of coerced marital sexuality which was not considered to be sexual violence. Gynecological examination, likely to trigger embarrassment and discomfort, was always perceived to be necessary and justified, and consent was implied.

Conclusion

This study can help question the appropriateness of professional practices related to the prevention of violence against women and gynecological examination practices. Any gynecological examination should be carried out within the framework of an equal relationship between caregiver and patient, for the general population and for women with a history of violence. It participates in preventing violence in the context of care, and more widely, in preventing violence against women.
From corners to community: exploring medical students’ sense of belonging through co-creation in clinical learning
Authors: Rae Valerie Isobel , Smith Samantha Eve , Hopkins Samantha Rae , Tallentire Victoria Ruth
Published: April 2024

Background

Belonging is critical for the development and wellbeing of medical students. Belonging, particularly within a ‘relational being’ paradigm, presents a significant challenge for students, especially within clinical learning environments. Co-creation is a learning relationship in which students are actively involved in the education process. It is inherently relational and promotes belonging within higher education environments. Little is known about utilising co-creationinthe curriculum, within medical education. The aim of this study was to explore medical students’ experience of co-creation of learning resources within the clinical learning environment.

Methods

Following ethical approval, medical students were invited to become co-creators of a learning bulletin resource, within the paediatric acute receiving unit, at a paediatric teaching hospital. Interpretative phenomenological analysis (IPA) was used to enable an in-depth exploration of how medical students experienced co-creation within the clinical learning environment. Medical students participated in semi-structured interviews about their experience, which were transcribed verbatim and analysed using IPA. The analysis integrated individual lived experiences into an analytic summary.

Results

Nine medical students participated. Three group experiential themes were identified: identity maturation; learning community and workplace integration. The support found within this co-created learning community, along with maturation of their identity, allowed the participants to experience a challenge to their existing worldview. This shift in perspective resulted in them responding and behaving in the workplace in new ways, which enabled them to belong as themselves in the clinical learning environment. These findings were situated within the developmental concept of self-authorship, as well as contributing to a new understanding of how co-creation promoted social integration.

Conclusions

Co-creation enabled students to learn in a meaningful way. The relational power of co-creation, can be harnessed to deliver participatory learning experiences, within our increasingly complex healthcare environment, to support the learning, development and integration of doctors of the future.
Seroevidence of SARS-CoV-2 spillback to rodents in Sarawak, Malaysian Borneo
Authors: Tan Cheng Siang , Adrus Madinah , Rahman Sultana Parvin Habeebur , Azman Haziq Izzuddin Muhamad , Abang Riz Anasthasia Alta
Published: April 2024

Background

SARS-CoV-2 is believed to have originated from a spillover event, where the virus jumped from bats to humans, leading to an epidemic that quickly escalated into a pandemic by early 2020. Despite the implementation of various public health measures, such as lockdowns and widespread vaccination efforts, the virus continues to spread. This is primarily attributed to the rapid emergence of immune escape variants and the inadequacy of protection against reinfection. Spillback events were reported early in animals with frequent contact with humans, especially companion, captive, and farmed animals. Unfortunately, surveillance of spillback events is generally lacking in Malaysia. Therefore, this study aims to address this gap by investigating the presence of SARS-CoV-2 neutralising antibodies in wild rodents in Sarawak, Malaysia.

Results

We analysed 208 archived plasma from rodents collected between from 2018 to 2022 to detect neutralising antibodies against SARS-CoV-2 using a surrogate virus neutralisation test, and discovered two seropositive rodents (Sundamys muelleri and Rattus rattus), which were sampled in 2021 and 2022, respectively.

Conclusion

Our findings suggest that Sundamys muelleri and Rattus rattus may be susceptible to natural SARS-CoV-2 infections. However, there is currently no evidence supporting sustainable rodent-to-rodent transmission.
Medicinal ethnoveterinary plants used for treating livestock ailments in the omo-gibe and rift valley basins of Ethiopia
Authors: Wendimu Abenezer , Bojago Elias , Abrham Yitbarek
Published: April 2024

Background

Traditional medical practices have been used to maintain animal health for millennia and have been passed down orally from generation to generation. In Ethiopia also, plants are the primary means by which the indigenous people in remote areas treat the illnesses of their animals. The present study was therefore, carried out to document the type and distribution of medicinal plants of the county.

Methods

To collect ethnobotanical information, a total of 205 informants (133 men and 72 women) were selected. Among these 121 traditional medicine practitioners, while the remaining 84 were selected through a systematic random sampling method. Ethnobotanical data were collected between January 2023 and August 2023 through semi-structured interviews, participant observation, guided filed walks and focus group discussions. Using descriptive statistics, the ethnobotanical data were analyzed for the Informant Consensus Factor (ICF) and Fidelity Level (FL) values, preference, and direct matrix rankings. SPSS 26.0 and PAST 4.11 software were used in data analysis.

Results

Totally, 78 ethnoveterinary medicinal plants distributed in 36 families were identified in the study area. Asteraceae was the dominant family with 9 species (14%), followed by Euphorbiaceae with 8 species (12%). Herbs 42(56%), wild collected 62 (66%), and leaf part (52%) made the highest share of the plant species.Hordeum vulgareL. had the highest fidelity level (FL = 98%) for treating bone fractures. Blackleg, bloat, and endoparsistes each had the highest values of the consensus factor among the informants (ICF = 1). According to preference ranking,Withania somniferawas the most potent remedy for treating blackleg. Knowledge of medicinal plants was shared through storytelling within families.

Conclusion

In the study area, there is broad access to traditional medicinal plants that can treat ailments in animals. Conservation efforts should be prioritized to protect medicinal plants from threats such as agricultural expansion, drought, and development. Further research should be conducted to explore the potential of different medicinal plants for treating common livestock ailments.
Poor statistical power in population-based association study of gene interaction
Authors: Ma Jiarui , Li Jian , Chen Yuqi , Yang Zhen , He Yungang
Published: April 2024

Background

Statistical epistasis, or “gene–gene interaction” in genetic association studies, means the nonadditive effects between the polymorphic sites on two different genes affecting the same phenotype. In the genetic association analysis of complex traits, nevertheless, the researchers haven’t found enough clues of statistical epistasis so far.

Methods

We developed a statistical model where the statistical epistasis was presented as an extra linkage disequilibrium between the polymorphic sites of different risk genes. The power of statistical test for identifying the gene–gene interaction was calculated and then compared in different hypothesis scenarios.

Results

Our results show the statistical power increases with the increasing of interaction coefficient, relative risk, and linkage disequilibrium with genetic markers. However, the power of interaction discovery is much lower than that of regular single-site association test. When rigorous criteria were employed in statistical tests, the identification of gene–gene interaction became a very difficult task. Since the criterion of significance was given to be p-value ≤ 5.0 × 10–8, the same as that of many genome-wide association studies, there is little chance to identify the gene–gene interaction in all kind of circumstances.

Conclusions

The lack of epistasis tends to be an inevitable result caused by the statistical principles of methods in the genetic association studies and therefore is the inherent characteristic of the research itself.
Melatonin improves influenza virus infection-induced acute exacerbation of COPD by suppressing macrophage M1 polarization and apoptosis
Authors: Xu Meng-Meng , Kang Jia-Ying , Wang Qiu-Yan , Zuo Xing , Tan Yuan-Yuan , Wei Yuan-Yuan , Zhang Da-Wei , Zhang Ling , Wu Hui-Mei , Fei Guang-He
Published: April 2024

Background

Influenza A viruses (IAV) are extremely common respiratory viruses for the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), in which IAV infection may further evoke abnormal macrophage polarization, amplify cytokine storms. Melatonin exerts potential effects of anti-inflammation and anti-IAV infection, while its effects on IAV infection-induced AECOPD are poorly understood.

Methods

COPD mice models were established through cigarette smoke exposure for consecutive 24 weeks, evaluated by the detection of lung function. AECOPD mice models were established through the intratracheal atomization of influenza A/H3N2 stocks in COPD mice, and were injected intraperitoneally with melatonin (Mel). Then, The polarization of alveolar macrophages (AMs) was assayed by flow cytometry of bronchoalveolar lavage (BAL) cells. In vitro, the effects of melatonin on macrophage polarization were analyzed in IAV-infected Cigarette smoking extract (CSE)-stimulated Raw264.7 macrophages. Moreover, the roles of the melatonin receptors (MTs) in regulating macrophage polarization and apoptosis were determined using MTs antagonist luzindole.

Results

The present results demonstrated that IAV/H3N2 infection deteriorated lung function (reduced FEV20,50/FVC), exacerbated lung damages in COPD mice with higher dual polarization of AMs. Melatonin therapy improved airflow limitation and lung damages of AECOPD mice by decreasing IAV nucleoprotein (IAV-NP) protein levels and the M1 polarization of pulmonary macrophages. Furthermore, in CSE-stimulated Raw264.7 cells, IAV infection further promoted the dual polarization of macrophages accompanied with decreased MT1 expression. Melatonin decreased STAT1 phosphorylation, the levels of M1 markers and IAV-NP via MTs reflected by the addition of luzindole. Recombinant IL-1β attenuated the inhibitory effects of melatonin on IAV infection and STAT1-driven M1 polarization, while its converting enzyme inhibitor VX765 potentiated the inhibitory effects of melatonin on them. Moreover, melatonin inhibited IAV infection-induced apoptosis by suppressing IL-1β/STAT1 signaling via MTs.

Conclusions

These findings suggested that melatonin inhibited IAV infection, improved lung function and lung damages of AECOPD via suppressing IL-1β/STAT1-driven macrophage M1 polarization and apoptosis in a MTs-dependent manner. Melatonin may be considered as a potential therapeutic agent for influenza virus infection-induced AECOPD.

Graphical Abstract

Schematic mechanisms underlying the regulatory effects of melatonin on macrophage polarization and apoptosis in IAV infection plus cigarette stimulation-induced AECOPD model.
Ketone body levels and its associations with cardiac markers following an acute myocardial infarction: a post hoc analysis of the EMMY trial
Authors: Aziz Faisal , Tripolt Norbert J. , Pferschy Peter N. , Scharnagl Hubert , Abdellatif Mahmoud , Oulhaj Abderrahim , Benedikt Martin , Kolesnik Ewald , von Lewinski Dirk , Sourij Harald
Published: April 2024

Background

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been suggested to exert cardioprotective effects in patients with heart failure, possibly by improving the metabolism of ketone bodies in the myocardium.

Methods

This post hoc analysis of the EMMY trial investigated the changes in serum β-hydroxybutyrate (3-βOHB) levels after acute myocardial infarction (AMI) in response to 26-week of Empagliflozin therapy compared to the usual post-MI treatment. In addition, the association of baseline and repeated measurements of 3-βOHB with cardiac parameters and the interaction effects of Empagliflozin were investigated. Cardiac parameters included N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), left ventricle end-systolic volume (LVESV), left ventricle end-diastolic volume (LVEDV), and left ventricular filling pressure (E/é ratio).

Results

The mean 3-βOHB levels increased from baseline (46.2 ± 3.0 vs. 51.7 ± 2.7) to 6 weeks (48.8 ± 2.2 vs. 42.0 ± 2.3) and 26 weeks (49.3 ± 2.2 vs. 35.8 ± 1.9) in the Empagliflozin group compared to a consistent decline in placebo over 26 weeks (pinteraction < 0.001). Baseline and longitudinal measurements of 3-βOHB were not significantly associated with NT-proBNP and E/é ratio. Baseline 3-βOHB value was negatively associated with LVEF (coefficient: − 0.464, 95%CI − 0.863;− 0.065, p = 0.023), while an increase in its levels over time was positively associated with LVEF (0.595, 0.156;1.035, 0.008). The baseline 3-βOHB was positively associated with LVESV (1.409, 0.186;2.632, 0.024) and LVEDV (0.640, − 1.170;− 2.449, 0.488), while an increase in its levels over time was negatively associated with these cardiac parameters (LVESV: − 2.099, − 3.443;− 0.755, 0.002; LVEDV: − 2.406, − 4.341;− 0.472, 0.015). Empagliflozin therapy appears to modify the association between 3-βOHB, LVEF (pinteraction = 0.090), LVESV (pinteraction = 0.134), and LVEDV (pinteraction = 0.168), particularly at 26 weeks; however, the results were not statistically significant.

Conclusion

This post hoc analysis showed that SGLT2i increased 3-βOHB levels after AMI compared to placebo. Higher baseline 3-βOHB levels were inversely associated with cardiac function at follow-up, whereas a sustained increase in 3-βOHB levels over time improved these markers. This highlights the importance of investigating ketone body metabolism in different post-MI phases. Although more pronounced effect of 3-βOHB on cardiac markers was observed in the SGLT2i group, further research is required to explore this interaction effect.
Antitumor mechanisms and future clinical applications of the natural product triptolide
Authors: Bao Shiwei , Yi Mei , Xiang Bo , Chen Pan
Published: April 2024

Triptolide (TPL) is a compound sourced from Tripterygium wilfordii Hook. F., a traditional Chinese medicinal herb recognized for its impressive anti-inflammatory, anti-angiogenic, immunosuppressive, and antitumor qualities. Notwithstanding its favorable attributes, the precise mechanism through which TPL influences tumor cells remains enigmatic. Its toxicity and limited water solubility significantly impede the clinical application of TPL. We offer a comprehensive overview of recent research endeavors aimed at unraveling the antitumor mechanism of TPL in this review. Additionally, we briefly discuss current strategies to effectively manage the challenges associated with TPL in future clinical applications. By compiling this information, we aim to enhance the understanding of the underlying mechanisms involved in TPL and identify potential avenues for further advancement in antitumor therapy.
R-loop and diseases: the cell cycle matters
Authors: Xu Yuqin , Jiao Yue , Liu Chengbin , Miao Rui , Liu Chunyan , Wang Yilong , Ma Chunming , Liu Jiao
Published: April 2024

The cell cycle is a crucial biological process that is involved in cell growth, development, and reproduction. It can be divided into G1, S, G2, and M phases, and each period is closely regulated to ensure the production of two similar daughter cells with the same genetic material. However, many obstacles influence the cell cycle, including the R-loop that is formed throughout this process. R-loop is a triple-stranded structure, composed of an RNA: DNA hybrid and a single DNA strand, which is ubiquitous in organisms from bacteria to mammals. The existence of the R-loop has important significance for the regulation of various physiological processes. However, aberrant accumulation of R-loop due to its limited resolving ability will be detrimental for cells. For example, DNA damage and genomic instability, caused by the R-loop, can activate checkpoints in the cell cycle, which in turn induce cell cycle arrest and cell death. At present, a growing number of factors have been proven to prevent or eliminate the accumulation of R-loop thereby avoiding DNA damage and mutations. Therefore, we need to gain detailed insight into the R-loop resolution factors at different stages of the cell cycle. In this review, we review the current knowledge of factors that play a role in resolving the R-loop at different stages of the cell cycle, as well as how mutations of these factors lead to the onset and progression of diseases.
Exclusion of HDAC1/2 complexes by oncogenic nuclear condensates
Authors: Kuang Junqi , Li Pengli , Zhai Ziwei , Fan Yixin , Xu HuaiYuan , Zhao Chengchen , Li Wei , Li Xiaoxi , Liang Zechuan , Huang Tao , Qin Yue , Gao Huiru , Ma Zhaoyi , Liu Dong , Zhong Guifa , Wang Bo , Liu Jing , Wang Jin , Tortorella Micky D. , Liao Baojian , Pei Duanqing
Published: April 2024

Nuclear condensates have been shown to regulate cell fate control, but its role in oncogenic transformation remains largely unknown. Here we show acquisition of oncogenic potential by nuclear condensate remodeling. The proto-oncogene SS18 and its oncogenic fusion SS18-SSX1 can both form condensates, but with drastically different properties and impact on 3D genome architecture. The oncogenic condensates, not wild type ones, readily exclude HDAC1 and 2 complexes, thus, allowing aberrant accumulation of H3K27ac on chromatin loci, leading to oncogenic expression of key target genes. These results provide the first case for condensate remodeling as a transforming event to generate oncogene and such condensates can be targeted for therapy.

One sentence summary: Expulsion of HDACs complexes leads to oncogenic transformation.
Associations between trans fatty acids and systemic immune-inflammation index: a cross-sectional study
Authors: Zhu Xiao-Feng , Hu Yu-Qi , Dai Zhi-Cheng , Li Xiu-Juan , Zhang Jing
Published: April 2024

Background

Previous studies have demonstrated that trans fatty acids (TFAs) intake was linked to an increased risk of chronic diseases. As a novel systemic inflammatory biomarker, the clinical value and efficacy of the systemic immune-inflammation index (SII) have been widely explored. However, the association between TFAs and SII is still unclear. Therefore, the study aims to investigate the connection between TFAs and SII in US adults.

Methods

The study retrieved data from the National Health and Nutrition Examination Survey (NHANES) for the years 1999–2000 and 2009–2010. Following the exclusion of ineligible participants, the study encompassed a total of 3047 individuals. The research employed a multivariate linear regression model to investigate the connection between circulating TFAs and SII. Furthermore, the restricted cubic spline (RCS) model was utilized to evaluate the potential nonlinear association. Subgroup analysis was also conducted to investigate the latent interactive factors.

Results

In this investigation, participants exhibited a mean age of 47.40 years, with 53.91% of them being female. Utilizing a multivariate linear regression model, the independent positive associations between the log2-transformed palmitelaidic acid, the log2 transformed-vaccenic acid, the log2-transformed elaidic acid, the log2-transformed linolelaidic acid, and the log2-transformed-total sum of TFAs with the SII (all P < 0.05) were noted. In the RCS analysis, no nonlinear relationship was observed between the log2-transformed palmitelaidic acid, the log2 transformed-vaccenic acid, the log2-transformed elaidic acid, the log2-transformed linolelaidic acid, the log2-transformed-total sum of TFAs and the SII (all P for nonlinear > 0.05). For the stratified analysis, the relationship between the circulating TFAs and the SII differed by the obesity status and the smoking status.

Conclusions

A positive association was investigated between three types of TFA, the sum of TFAs, and the SII in the US population. Additional rigorously designed studies are needed to verify the results and explore the potential mechanism.
Implementation opportunities and challenges to piloting a community-based drug-checking intervention for sexual and gender minority men in Vancouver, Canada: a qualitative study
Authors: Coulaud Pierre-julien , Chayama Koharu Loulou , Schwartz Cameron , Purdie Aaron , Lysyshyn Mark , Ti Lianping , Knight Rod
Published: April 2024

Background

In response to the overdose crisis, a collaborative group of two community-based organizations, a health authority and a research institute in Vancouver, Canada, implemented a pilot community-based drug checking (CBDC) intervention for sexual and gender minority (SGM) men. This study identified key factors that influenced the implementation of the CBDC intervention, including opportunities and challenges.

Methods

We conducted semi-structured interviews with seven pertinent parties involved in the CBDC, including policymakers, researchers and representatives from community-based organizations. These interviews were coded and analyzed using domains and constructs of the Consolidated Framework for Implementation Research.

Results

While drug-related stigma was identified as a challenge to deliver drug checking services, participants described the context of the overdose crisis as a key facilitator to engage collaboration between relevant organizations (e.g., health authorities, medical health officers, community organizations) to design, resource and implement the CBDC intervention. The implementation of the CBDC intervention was also influenced by SGM-specific needs and resources (e.g., lack of information about the drug supply). The high level of interest of SGM organizations in providing harm reduction services combined with the need to expand drug checking into community spaces represented two key opportunities for the CBDC intervention. Here, SGM organizations were recognized as valued partners that fostered a broader culture of harm reduction. Participants’ emphasis that knowing the composition of one’s drugs is a “right to know”, particularly in the context of a highly contaminated illicit drug market, emerged as a key implementation factor. Lastly, participants emphasized the importance of involving SGM community groups at all stages of the implementation process to ensure that the CBDC intervention is appropriately tailored to SGM men.

Conclusions

The context of the overdose crisis and the involvement of SGM organizations were key facilitators to the implementation of a drug checking intervention in SGM community spaces. This study offers contextualized understandings about how SGM knowledge and experiences can contribute to implement tailored drug checking interventions.
Obesity-induced blood-brain barrier dysfunction: phenotypes and mechanisms
Authors: Feng Ziying , Fang Cheng , Ma Yinzhong , Chang Junlei
Published: April 2024

Obesity, a burgeoning global health issue, is increasingly recognized for its detrimental effects on the central nervous system, particularly concerning the integrity of the blood-brain barrier (BBB). This manuscript delves into the intricate relationship between obesity and BBB dysfunction, elucidating the underlying phenotypes and molecular mechanisms. We commence with an overview of the BBB’s critical role in maintaining cerebral homeostasis and the pathological alterations induced by obesity. By employing a comprehensive literature review, we examine the structural and functional modifications of the BBB in the context of obesity, including increased permeability, altered transport mechanisms, and inflammatory responses. The manuscript highlights how obesity-induced systemic inflammation and metabolic dysregulation contribute to BBB disruption, thereby predisposing individuals to various neurological disorders. We further explore the potential pathways, such as oxidative stress and endothelial cell dysfunction, that mediate these changes. Our discussion culminates in the summary of current findings and the identification of knowledge gaps, paving the way for future research directions. This review underscores the significance of understanding BBB dysfunction in obesity, not only for its implications in neurodegenerative diseases but also for developing targeted therapeutic strategies to mitigate these effects.
The impact of anxiety on gait impairments in Parkinson’s disease: insights from sensor-based gait analysis
Authors: Zhang Xiaodan , Jin Yulan , Wang Mateng , Ji Chengcheng , Chen Zhaoying , Fan Weinv , Rainer Timothy Hudson , Guan Qiongfeng , Li Qianyun
Published: April 2024

Background

Sensor-based gait analysis provides a robust quantitative tool for assessing gait impairments and their associated factors in Parkinson’s disease (PD). Anxiety is observed to interfere with gait clinically, but this has been poorly investigated. Our purpose is to utilize gait analysis to uncover the effect of anxiety on gait in patients with PD.

Methods

We enrolled 38 and 106 PD patients with and without anxiety, respectively. Gait parameters were quantitively examined and compared between two groups both in single-task (ST) and dual-task (DT) walking tests. Multiple linear regression was applied to evaluate whether anxiety independently contributed to gait impairments.

Results

During ST, PD patients with anxiety presented significantly shorter stride length, lower gait velocity, longer stride time and stance time, longer stance phase, smaller toe-off (TO) and heel-strike (HS) angles than those without anxiety. While under DT status, the differences were diminished. Multiple linear regression analysis demonstrated that anxiety was an independent factor to a serials of gait parameters, particularly ST-TO (B = -2.599, (-4.82, -0.38)), ST-HS (B = -2.532, (-4.71, -0.35)), ST-TO-CV (B = 4.627, (1.71, 7.64)), ST-HS-CV(B = 4.597, (1.66, 7.53)), ST stance phase (B = 1.4, (0.22, 2.58)), and DT stance phase (B = 1.749, (0.56, 2.94)).

Conclusion

Our study discovered that anxiety has a significant impact on gait impairments in PD patients, especially exacerbating shuffling steps and prolonging stance phase. These findings highlight the importance of addressing anxiety in PD precision therapy to achieve better treatment outcomes.