bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between drinking status and risk of kidney stones among United States adults: NHANES 2007–2018
Authors: Wei Baian , Tan Wenyue , He Shuien , Yang Shijian , Gu Chiming , Wang Shusheng
Published: March 2024

Objective

This study aimed to investigate the relationship between drinking status and kidney stones occurrence among United States (US) adults who consume alcohol.

Methods

We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES 2007–2018). Questionnaires yielded information on alcohol consumption and kidney health. Drinking status was categorized into four groups—former, mild, moderate, and heavy—based on alcohol consumption patterns. The aim was to explore the relationship between drinking status and the prevalence of kidney stones occurrence. For this analysis, we examined a group of individuals diagnosed with kidney stones. With survey weights applied, the total weight of the group was 185,690,415.

Results

We used logistic regression to measure the relationship between drinking status and the likelihood of developing kidney stones. In a fully adjusted model, former drinkers were less likely to have previously experienced kidney stones (OR 0.762, 95% CI 0.595–0.977, P < 0.05). In subgroup analysis, heavy alcohol consumption was associated with a significantly reduced likelihood of kidney stones occurrence in various populations. The adjusted odds ratios (with 95% confidence intervals) of kidney stones risk for heavy alcohol consumption were 0.745 (0.566–0.981) for young individuals, 0.566 (0.342–0.939) for older individuals, 0.708 (0.510–0.981) for individuals of white race, 0.468 (0.269–0.817) for individuals with underweight/normal BMI, 0.192 (0.066–0.560) for widowed people, 0.538 (0.343–0.843) for smoking individuals, 0.749 (0.595–0.941) for individuals without a cancer history, and 0.724 (0.566–0.925) for individuals without a stroke history.

Conclusions

In US adults who consume alcohol, a negative linear relationship is apparent between drinking status and the prevalence of kidney stones, with heavy drinking showing a lower prevalence compared to former drinkers. However, the causal relationship between drinking status and kidney stones requires further investigation in future research endeavors.
Bronchodilator reversibility testing in morbidly obese non-smokers: a comparative study– few concerns
Authors: Balan Divya , Shetty Manish R , Mohan Manu K
Published: March 2024

This is a letter in response to an article by Ahmed et al., which concluded that in comparison to salbutamol, Fluticasone/salmeterol combination increases FEV1, FEV1% of predicted, and FEV1/FVC ratio, however it did not offer novel insights, as both agents met the 12%- and 200-mL reversibility benchmarks and Concerns about incorporating a combination medication that includes an inhaled corticosteroid, inhaled corticosteroids are not typically associated with bronchodilation.
Does aligner refinement have the same efficiency in deep bite correction?: A retrospective study
Authors: Kang Jessica , Jeon Hyeran Helen , Shahabuddin Nishat
Published: March 2024

Background

Refinements are very common in clear aligner treatments. The aim of this study is to assess whether the predictability of deep overbite correction is similar over several refinements using clear aligners (Invisalign, Align Technology, San Jose, Calif) and examine the accuracy of vertical movement and inclination change of individual teeth.

Methods

This retrospective study included 20 deep bite patients (7M and 13F; 32.63 ± 11.88 years old; an initial overbite of 5.09 ± 0.98 mm), consecutively treated from September 2016 and March 2023, who completed at least two sets of aligners, including refinements. The initial, predicted, and achieved models were exported from ClinCheck or OrthoCAD (Cadent Inc, Carlstadt, NJ) and superimposed via best-fit surface-based registration using SlicerCMF (version 4.9.0; cmf.slicer.org). We also examined 15 out of 20 patients who completed treatments. The overbite correction and changes in vertical movement and inclination for individual teeth were measured. Descriptive statistics and a paired t-test or Wilcoxon signed-rank test were performed. P < 0.05 was considered statistically significant.

Results

The mean accuracy of overbite correction was 37.63% after 1st set, followed by 11.19%, 6.32%, and 13.80% (2nd-4th sets), respectively. There were statistically significant differences between the predicted and achieved vertical movements and inclination changes for all teeth for the 1st and 2nd sets. For the completed cases, the mean overbite correction was 38.54% compared to the initially planned overbite correction, which is similar to one of the 1st set. Still, the vertical movements and inclination changes of all teeth present statistically significant differences between the initially planned and finally achieved movements except for maxillary lateral incisor torque.

Conclusions

The most overbite correction occurs during the 1st set of aligners, and refinement treatment does not significantly improve the deep bite correction.
Outcome of nonsurgical management of large cyst-like periapical lesions using a modified apical negative pressure irrigation system: a case series study
Authors: Ling Danhua , Chen Yun , Chen Gongpei , Zhang Yanzhen , Wang Yanhong , Wang Ying , He Fuming
Published: March 2024

Objective

To assess the effectiveness of a self-constructed modified apical negative pressure irrigation (ANPI) system employing commonly used clinical instruments in nonsurgical root canal therapy (NSRCT) for large cyst-like periapical lesions (LCPLs).

Methods

From 2017 to 2022, 35 patients diagnosed with LCPLs (5-15 mm) via preoperative clinical and radiographic evaluations of endodontic origin underwent NSRCT combined with ANPI. These patients were subjected to postoperative clinical and radiographic follow-up at 3 months, 6 months, 1 year, 2 years, 3 years, and 4 years, with a CBCT scan specifically conducted at 6-month follow-up. Through the reconstruction of three-dimensional cone beam computed tomography (CBCT) data, an early prognosis was facilitated by monitoring changes in lesion volume. Various treatment predictors—including sex, type of treatment, lesion size, preoperative pain, jaw, type of teeth involved, sealer extrusion, and the number of root canals—were meticulously analyzed. The evaluation of post-treatment outcomes leveraged both clinical observations and radiographic data collected during the follow-up periods. The Kruskal‒Wallis test and one-way ANOVA were also conducted to determine the independent factors influencing treatment outcomes. A significance level of 5% was established.

Results

Thirty-five teeth from 35 patients with a median age of 28 years (range 24–34) were treated; the median follow-up duration was 19 months (range 12–26). The overall success rate was 91.4%, with a median lesion reduction of 77.0% (range 54.2–96.4%) at 6 months. Patients under 30 years of age exhibited a significantly greater success rate than older patients did (100.0% vs. 80.0%, p = 0.037). Other factors, such as sex, jaw, treatment type, preoperative pain, cyst size, tooth location, sealer extrusion, and the number of roots, did not significantly impact treatment outcomes.

Conclusions

Despite limitations related to the observational case-series study design and relatively small sample size, our findings suggest that utilizing the ANPI in the NSRCT for LCPLs may hold promise. The notably higher success rate in patients younger than 30 years is worth noting.
The impact of varying levels of residual disease following cytoreductive surgery on survival outcomes in patients with ovarian cancer: a meta-analysis
Authors: Chase Dana M. , Mahajan Anadi , Scott David Alexander , Hawkins Neil , Kalilani Linda
Published: March 2024

Background

Residual disease following cytoreductive surgery in patients with ovarian cancer has been associated with poorer survival outcomes compared with no residual disease. We performed a meta-analysis to assess the impact of varying levels of residual disease status on survival outcomes in patients with ovarian cancer who have undergone primary cytoreductive surgery or interval cytoreductive surgery in the setting of new therapies for this disease.

Methods

Medline, Embase, and Cochrane databases (January 2011 – July 2020) and grey literature, bibliographic and key conference proceedings, were searched for eligible studies. Fixed and random-effects meta-analyses compared progression and survival by residual disease level across studies. Heterogeneity between comparisons was explored via type of surgery, disease stage, and type of adjuvant chemotherapy.

Results

Of 2832 database and 16 supplementary search articles screened, 50 studies were selected; most were observational studies. The meta-analysis showed that median progression-free survival and overall survival decreased progressively with increasing residual disease (residual disease categories of 0 cm, > 0–1 cm and > 1 cm). Compared with no residual disease, hazard ratios (HR) for disease progression increased with increasing residual disease category (1.75 [95% confidence interval: 1.42, 2.16] for residual disease > 0–1 cm and 2.14 [1.34, 3.39] for residual disease > 1 cm), and also for reduced survival (HR versus no residual disease, 1.75 [ 1.62, 1.90] for residual disease > 0–1 cm and 2.32 [1.97, 2.72] for residual disease > 1 cm). All comparisons were significant (p < 0.05). Subgroup analyses showed an association between residual disease and disease progression/reduced survival irrespective of type of surgery, disease stage, or type of adjuvant chemotherapy.

Conclusions

This meta-analysis provided an update on the impact of residual disease following primary or interval cytoreductive surgery, and demonstrated that residual disease was still highly predictive of progression-free survival and overall survival in adults with ovarian cancer despite changes in ovarian cancer therapy over the last decade. Higher numerical categories of residual disease were associated with reduced survival than lower categories.
Knowledge, attitudes and practices about research misconduct among medical residents in southwest China: a cross-sectional study
Authors: Chen Lulin , Li Yizhao , Wang Jie , Li Yue , Tan Xiaoli , Guo Xiaoyan
Published: March 2024

Background

With the emergence of numerous scientific outputs, growing attention is paid to research misconduct. This study aimed to investigate knowledge, attitudes and practices about research misconduct among medical residents in southwest China.

Methods

A cross-sectional study was conducted in southwest China from November 2022 through March 2023. The links to the questionnaire were sent to the directors of the teaching management department in 17 tertiary hospitals. Answers were collected and analyzed. Logistic regression analysis was performed to explore the factors associated with research misconduct among residents.

Results

6200 residents were enrolled in the study, and 88.5% of participants attended a course on research integrity, but 53.7% of participants admitted to having committed at least one form of research misconduct. Having a postgraduate or above, publishing papers as the first author or corresponding author, attending a course on research integrity, lower self-reported knowledge on research integrity and lower perceived consequences for research misconduct were positively correlated to research misconduct. Serving as a primary investigator for a research project was negatively associated with research misconduct. Most residents (66.3%) agreed that the reason for research misconduct is that researchers lack research ability.

Conclusions

The high self-reported rate of research misconduct among residents in southwest China underscores a universal necessity for enhancing research integrity courses in residency programs. The ineffectiveness of current training in China suggests a possible global need for reevaluating and improving educational approaches to foster research integrity. Addressing these challenges is imperative not only for the credibility of medical research and patient care in China but also for maintaining the highest ethical standards in medical education worldwide. Policymakers, educators, and healthcare leaders on a global scale should collaborate to establish comprehensive strategies that ensure the responsible conduct of research, ultimately safeguarding the integrity of medical advancements and promoting trust in scientific endeavors across borders.
Exploring homecare leaders’ risk perception and the link to resilience and adaptive capacity: a multiple case study
Authors: Idsøe-Jakobsen Ingvild , Dombestein Heidi , Wiig Siri
Published: March 2024

Background

Home-based healthcare is considered crucial for the sustainability of healthcare systems worldwide. In the homecare context, however, adverse events may occur due to error-prone medication management processes and prevalent healthcare-associated infections, falls, and pressure ulcers. When dealing with risks in any form, it is fundamental for leaders to build a shared situational awareness of what is going on and what is at stake to achieve a good outcome. The overall aim of this study was to gain empirical knowledge of leaders’ risk perception and adaptive capacity in homecare services.

Methods

The study applied a multiple case study research design. We investigated risk perception, leadership, sensemaking, and decision-making in the homecare services context in three Norwegian municipalities. Twenty-three leaders were interviewed. The data material was analyzed using thematic analysis and interpreted in a resilience perspective of work-as-imagined versus work-as-done.

Results

There is an increased demand on homecare services and workers’ struggle to meet society’s high expectations regarding homecare’s responsibilities. The leaders find themselves trying to maneuver in these pressing conditions in alignment with the perceived risks. The themes emerging from analyzed data were: ‘Risk and quality are conceptualized as integral to professional work’, ‘Perceiving and assessing risk imply discussing and consulting each other– no one can do it alone’ and ‘Leaders keep calm and look beyond the budget and quality measures by maneuvering within and around the system’. Different perspectives on patients’ well-being revealed that the leaders have a large responsibility for organizing the healthcare soundly and adequately for each home-dwelling patient. Although the leaders did not use the term risk, discussing concerns and consulting each other was a profound part of the homecare leaders’ sense of professionalism.

Conclusions

The leaders’ construction of a risk picture is based on using multiple signals, such as measurable vital signs and patients’ verbal and nonverbal expressions of their experience of health status. The findings imply a need for more research on how national guidelines and quality measures can be implemented better in a resilience perspective, where adaptive capacity to better align work-as-imagined and work-as-done is crucial for high quality homecare service provision.
Serological investigation and isolation of Salmonella abortus equi in horses in Xinjiang
Authors: Mai Zhanhai , Fu Han , Miao Ronghao , Lu Chong , Zhang Xiaosong , Yuan Ziwen , Ji Peng , Hua Yongli , Wang Chen , Ma Yuhui , Deng Haifeng , Wei Yanming
Published: March 2024

Background

Salmonella enterica subspecies enterica serovar abortus equi (S. abortus equi) is one of the main pathogens that causes abortion in pregnant horses and donkeys, which was highly infectious and greatly restricts the healthy development of the horse industry.

Objectives

In order to investigate the prevalence and biological characteristics of S. abortus equi in different regions and breeds of horses in Xinjiang.

Methods

This study conducted ELISA detection of S. abortus equi antibodies on serum samples of 971 horses collected from three large-scale horse farms and five free-range horse farms in Yili Prefecture and Bayingol Mongolian Autonomous Prefecture of Xinjiang from 2020 to 2023. On this basis, bacterial isolation, culture, identification, and drug sensitivity tests were conducted on 42 samples of aborted foal tissues and 23 mare vaginal swabs.

Results

The results showed that the positive rate of S. abortus equi antibody was as high as 20.91% in 971 horse serum samples. Among them, the positive rate in the Ili region (29.09%) was significantly higher than that in the Bayingole region (11.24%), and the positive rate in mares (22.45%) was higher than that in stallions (14.05%). In terms of horse breeds, the positive rates of self-propagating thoroughbred horses, half-bred horses, Ili horses and Yanqi horses were 43.22%, 28.81%, 14.72% and 11.24% respectively. In addition, S. abortus equi was more susceptible to juvenile and elderly horses, with positive rates of 70.00%and 41.86%, respectively, both of which were significantly higher than young (10.97%) and adult (19.79%) horses. Further, 9 strains of S. abortus equi were obtained through bacterial isolation, culture and identification, which were resistant to five antibiotics (Clarithromycin, Clindamycin, penicillin, Sulfamethoxazole and Rifampicin), and sensitive to 13 antimicrobial agents (Amoxicillin, Ciprofloxacin and Gentamicin, et al.).

Conclusion

There was a high infection rate of S. abortus equi in Ili Prefecture and self-propagating thoroughbred horses, and juvenile or old mares were more susceptible, which will provide scientific basis for the prevention of S. abortus equi infection in different regions and breeds of horses in Xinjiang.
MCT4-dependent lactate transport: a novel mechanism for cardiac energy metabolism injury and inflammation in type 2 diabetes mellitus
Authors: Ma Xiu Mei , Geng Kang , Wang Peng , Jiang Zongzhe , Law Betty Yuen-Kwan , Xu Yong
Published: March 2024

Diabetic cardiomyopathy (DCM) is a major contributor to mortality in diabetic patients, characterized by a multifaceted pathogenesis and limited therapeutic options. While lactate, a byproduct of glycolysis, is known to be significantly elevated in type 2 diabetes, its specific role in DCM remains uncertain. This study reveals an abnormal upregulation of monocarboxylate transporter 4 (MCT4) on the plasma membrane of cardiomyocytes in type 2 diabetes, leading to excessive lactate efflux from these cells. The disruption in lactate transport homeostasis perturbs the intracellular lactate-pyruvate balance in cardiomyocytes, resulting in oxidative stress and inflammatory responses that exacerbate myocardial damage. Additionally, our findings suggest increased lactate efflux augments histone H4K12 lactylation in macrophages, facilitating inflammatory infiltration within the microenvironment. In vivo experiments have demonstrated that inhibiting MCT4 effectively alleviates myocardial oxidative stress and pathological damage, reduces inflammatory macrophage infiltration, and enhances cardiac function in type 2 diabetic mice. Furthermore, a clinical prediction model has been established, demonstrating a notable association between peripheral blood lactate levels and diastolic dysfunction in individuals with type 2 diabetes. This underscores the potential of lactate as a prognostic biomarker for DCM. Ultimately, our findings highlight the pivotal involvement of MCT4 in the dysregulation of cardiac energy metabolism and macrophage-mediated inflammation in type 2 diabetes. These insights offer novel perspectives on the pathogenesis of DCM and pave the way for the development of targeted therapeutic strategies against this debilitating condition.
Beyond a spec: assessing heterogeneity in the unregulated opioid supply
Authors: Gozdzialski Lea , Louw Rebecca , Kielty Collin , Margolese Ava , Poarch Eric , Sherman Miriam , Cameron Fred , Gill Chris , Wallace Bruce , Hore Dennis
Published: March 2024

Background

Drug checking services aim to provide compositional information for the illicit drug supply and are being employed in public health responses to extreme rates of overdose associated with fentanyl within street opioids. The technologies used within these services range from basic qualitative tests, such as immunoassay test strips, to comprehensive quantitative analyses, such as mass spectrometry. In general, there is concern that heterogeneity of a drug mixture adds significant uncertainty when using drug checking results based on a small subsamples. The presence of hot spots of active drug components in this context is often termed the ‘chocolate chip cookie effect’. Establishing the limitations of the service are essential for interpretation of the results.

Methods

This study assesses the consequence of drug heterogeneity and sampling of consumer level opioid purchased in Victoria, British Columbia ($$n=21$$

n
=
21

, 50–100 mg each) on quantitative fentanyl results determined from testing with paper spray mass spectrometry.

Results:

Using descriptive statistics, such as relative standard deviation and interquartile range, the results demonstrate varied distributions of fentanyl concentrations within a single drug batch. However, the presence of hot spots, defined as outliers, were relatively rare.

Conclusions

This study found that the variability in fentanyl concentration from drug heterogeneity and sampling is greater than that attributed to the analytical technique. On a practical level, this provides data to help guide communication of limitations of drug checking services, supporting the aim of trust and transparency between services and people who use drugs. However, if drug checking services continue to be restricted from fully engaging with the reality of manufacturing, buying, selling, mixing and dosing practices, the accuracy, usefulness, and impact will always be limited.
Pregnancy and obstetric outcomes of dichorionic triamniotic triplet pregnancies with selective foetal reduction after assisted reproductive technology
Authors: Liu Shuhua , Xu Qianhua , Liu Dehong , Li Qiuru , Qian Jingyu , Zhang Bin , Chen Xianxia
Published: March 2024

Background

It is generally beneficial and recommended that dichorionic triamniotic (DCTA) triplet pregnancies be reduced to monochorionic (MC) twin or singleton pregnancies after assisted reproductive technology (ART). However, some infertile couples still have a firm desire to retain twins. For this reason, the best foetal reduction strategies need to be available for infertile couples and clinicians. Given that data on the elective reduction of DCTA triplet pregnancies to twin pregnancies are scarce, we investigated the outcomes of elective reduction of DCTA triplet pregnancies through the retrospective analysis of previous data.

Method

Patients with DCTA triplet pregnancies who underwent elective foetal reduction between January 2012 and June 2020 were recruited. A total of 67 eligible patients with DCTA triplet pregnancies were divided into two groups: a DCTA-to-dichorionic diamniotic (DCDA) twin group (n = 38) and a DCTA-to-monochorionic diamniotic (MCDA) twin group (n = 29); the basic clinical data of the two groups were collected for comparison.

Results

Compared with the DCDA-to-MCDA twin group, the DCTA-to-DCDA twin group had lower rates of complete miscarriage (7.89% versus 31.03%,p = 0.014), early complete miscarriage (5.26% versus 24.14%,p = 0.034), late preterm birth (25.71% versus 65.00%,p = 0.009) and very low birth weight (0 versus 11.11%,p = 0.025). In addition, the DCTA-to-DCDA twin group had higher rates of full-term delivery (65.71% versus 25.00%,p = 0.005), survival (92.11% versus 68.97%,p = 0.023), and taking the babies home (92.11% versus 68.97%,p = 0.023) than did the DCTA-to-MCDA twin group. In terms of neonatal outcomes, a significantly greater gestational age (38.06 ± 2.39 versus 36.28 ± 2.30,p = 0.009), average birth weight (3020.77 ± 497.33 versus 2401.39 ± 570.48,p < 0.001), weight of twins (2746.47 ± 339.64 versus 2251.56 ± 391.26,p < 0.001), weight of the larger neonate (2832.94 ± 320.58 versus 2376.25 ± 349.95,p < 0.001) and weight of the smaller neonate (2660.00 ± 345.34 versus 2126.88 ± 400.93,p < 0.001) was observed in the DCTA-to-DCDA twin group compared to the DCTA-to-MCDA twin group.

Conclusion

The DCTA-to-DCDA twin group had better pregnancy and neonatal outcomes than the DCTA-to-MCDA twin group. This reduction approach may be beneficial for patients with dichorionic triamniotic triplet pregnancies who have a strong desire to have DCDA twins.
Dual deficiency of melatonin and dihydrotestosterone promotes stromal cell damage and mediates prostatitis via the cGAS-STING pathway in sleep-deprived mice
Authors: Chen Jia , Ma Wenming , Yue Shaoyu , Li Dongsheng , Chen Lei , Zhang Cheng , Guan Yu , Li Chun , Jiang Changqin , Liao Guiyi , Liang Chaozhao , Wang Hui , Tai Sheng
Published: March 2024

Purpose

Prostatitis is a highly prevalent condition that seriously affects men’s physical and mental health. Although epidemiological investigations have provided evidence of a correlation between insufficient sleep and prostatitis, the pathogenesis of prostatitis remains unclear. We sought to identify the underlying mechanism involved and identify a promising therapeutic target.

Methods

Sleep deprivation (SD) was utilized to establish a mouse model of insufficient sleep in a special device. Prostatitis was observed at different time points post-SD. The degree of prostatitis was evaluated by pathological section and behavioural tests. Using immunofluorescence, western blot, and proteomic analyses, the underlying mechanism of SD-related prostatitis was investigated, and the development and therapeutic target of prostatitis were elucidated.

Results

SD, as an initial pathological trigger, resulted in a reduction in dihydrotestosterone and melatonin levels. Proteomic analysis revealed that the cGAS-STING pathway may play a significant role in inducing prostatitis. The subsequent results illustrated that the dual reduction in dihydrotestosterone and melatonin led to an accumulation of reactive oxygen species and the release of mitochondrial DNA (mt-DNA). The accumulation of mt-DNA activated the cGAS-STING pathway, which recruited inflammatory cells into the prostatic stroma through the secretion of interferon-β. Consequently, an inflammatory microenvironment was formed, ultimately promoting the development of prostatitis. Notably, mice with SD-induced prostatitis gradually recovered to a normal state within 7 days of recovery sleep. However, after being subjected to SD again, these mice tended to have a more pronounced manifestation of prostatitis within a shorter timeframe, which suggested that prostatitis is prone to relapse.

Conclusions

The cGAS-STING pathway activated by dual deficiency of dihydrotestosterone and melatonin plays a comprehensive inflammatory role in SD-related prostatitis. This research provides valuable insights into the pathogenesis, therapeutic targets, and prevention strategies of prostatitis.
Endothelial β-catenin upregulation and Y142 phosphorylation drive diabetic angiogenesis via upregulating KDR/HDAC9
Authors: Chen Zhenfeng , Lin Bingqi , Yao Xiaodan , Weng Jie , Liu Jinlian , He Qi , Song Ke , Zhou Chuyu , Zuo Zirui , Huang Xiaoxia , Liu Zhuanhua , Huang Qiaobing , Xu Qiulin , Guo Xiaohua
Published: March 2024

Background

Diabetic angiogenesis is closely associated with disabilities and death caused by diabetic microvascular complications. Advanced glycation end products (AGEs) are abnormally accumulated in diabetic patients and are a key pathogenic factor for diabetic angiogenesis. The present study focuses on understanding the mechanisms underlying diabetic angiogenesis and identifying therapeutic targets based on these mechanisms.

Methods

In this study, AGE-induced angiogenesis serves as a model to investigate the mechanisms underlying diabetic angiogensis. Mouse aortic rings, matrigel plugs, and HUVECs or 293T cells were employed as research objects to explore this pathological process by using transcriptomics, gene promoter reporter assays, virtual screening and so on.

Results

Here, we found that AGEs activated Wnt/β-catenin signaling pathway and enhanced the β-catenin protein level by affecting the expression of β-catenin degradation-related genes, such as FZDs (Frizzled receptors), LRPs (LDL Receptor Related Proteins), and AXIN1. AGEs could also mediate β-catenin Y142 phosphorylation through VEGFR1 isoform5. These dual effects of AGEs elevated the nuclear translocation of β-catenin and sequentially induced the expression of KDR (Kinase Insert Domain Receptor) and HDAC9 (Histone Deacetylase 9) by POU5F1 and NANOG, respectively, thus mediating angiogenesis. Finally, through virtual screening, Bioymifi, an inhibitor that blocks VEGFR1 isoform5-β-catenin complex interaction and alleviates AGE-induced angiogenesis, was identified.

Conclusion

Collectively, this study offers insight into the pathophysiological functions of β-catenin in diabetic angiogenesis.
Abcg2a is the functional homolog of human ABCG2 expressed at the zebrafish blood–brain barrier
Authors: Thomas Joanna R. , Frye William J. E. , Robey Robert W. , Warner Andrew C. , Butcher Donna , Matta Jennifer L. , Morgan Tamara C. , Edmondson Elijah F. , Salazar Paula B. , Ambudkar Suresh V. , Gottesman Michael M.
Published: March 2024

Background

A principal protective component of the mammalian blood–brain barrier (BBB) is the high expression of the multidrug efflux transporters P-glycoprotein (P-gp, encoded by ABCB1) and ABCG2 (encoded by ABCG2) on the lumenal surface of endothelial cells. The zebrafish P-gp homolog Abcb4 is expressed at the BBB and phenocopies human P-gp. Comparatively little is known about the four zebrafish homologs of the human ABCG2 gene: abcg2a, abcg2b, abcg2c, and abcg2d. Here we report the functional characterization and brain tissue distribution of zebrafish ABCG2 homologs.

Methods

To determine substrates of the transporters, we stably expressed each in HEK-293 cells and performed cytotoxicity and fluorescent efflux assays with known ABCG2 substrates. To assess the expression of transporter homologs, we used a combination of RNAscope in situ hybridization probes and immunohistochemistry to stain paraffin-embedded sections of adult and larval zebrafish.

Results

We found Abcg2a had the greatest substrate overlap with ABCG2, and Abcg2d appeared to be the least functionally similar. We identified abcg2a as the only homolog expressed at the adult and larval zebrafish BBB, based on its localization to claudin-5 positive brain vasculature.

Conclusions

These results demonstrate the conserved function of zebrafish Abcg2a and suggest that zebrafish may be an appropriate model organism for studying the role of ABCG2 at the BBB.
LysipheN: a gravimetric IoT device for near real-time high-frequency crop phenotyping: a case study on common beans
Authors: Pineda-Castro Duvan , Diaz Harold , Soto Jonatan , Urban Milan Oldřich
Published: March 2024

Climate instability directly affects agro-environments. Water scarcity, high air temperature, and changes in soil biota are some factors caused by environmental changes. Verified and precise phenotypic traits are required for assessing the impact of various stress factors on crop performance while keeping phenotyping costs at a reasonable level. Experiments which use a lysimeter method to measure transpiration efficiency are often expensive and require complex infrastructures. This study presents the development and testing process of an automated, reliable, small, and low-cost prototype system using IoT with high-frequency potential in near-real time. Because of its waterproofness, our device—LysipheN—assesses each plant individually and can be deployed for experiments in different environmental conditions (farm, field, greenhouse, etc.). LysipheN integrates multiple sensors, automatic irrigation according to desired drought scenarios, and a remote, wireless connection to monitor each plant and device performance via a data platform. During testing, LysipheN proved to be sensitive enough to detect and measure plant transpiration, from early to ultimate plant developmental stages. Even though the results were generated on common beans, the LysipheN can be scaled up/adapted to other crops. This tool serves to screen transpiration, transpiration efficiency, and transpiration-related physiological traits. Because of its price, endurance, and waterproof design, LysipheN will be useful in screening populations in a realistic ecological and breeding context. It operates by phenotyping the most suitable parental lines, characterizing genebank accessions, and allowing breeders to make a target-specific selection using functional traits (related to the place where LysipheN units are located) in line with a realistic agronomic background.
Thoracoscopic McKeown esophagectomy in a patient with an azygos lobe
Authors: Nakashima Rie , Tajima Kohei , Koyanagi Kazuo , Kazuno Akihito , Yamamoto Miho , Shoji Yoshiaki , Yatabe Kentaro , Kanamori Kohei , Ogimi Mika , Nabeshima Kazuhito , Nakamura Kenji , Mori Masaki
Published: March 2024

Background

The azygos lobe is a relatively rare anatomical variation, and there have been no reports, until date, of thoracoscopic McKeown esophagectomy for esophageal cancer in a patient with an azygos lobe. The azygos lobe can be diagnosed by chest X-ray or CT, and is usually not associated with any symptoms. However, surgeons should be aware that transthoracic surgical procedures in patients with an azygos lobe could be associated with a high risk of complications.

Case presentation

An 83-years-old man was brought to our emergency room with fever, severe headache, and difficulty in moving. MRI revealed a brain abscess, which was treated by abscess drainage and systemic antibiotic treatment. Further examinations to determine the cause of the brain abscess revealed esophageal cancer. In addition, CT revealed an azygos lobe in the right thoracic cavity. Although intrathoracic adhesions were anticipated on account of a previous history of bacterial pyothorax, we decided to perform esophagectomy via a thoracoscopic approach. Despite the difficulty in dissecting the intrathoracic adhesions, we were able to obtain the surgical field thoracoscopically. Then, we found the azygos lobe, as diagnosed preoperatively, and the azygos vein was supported by the mesentery draining into the superior vena cava. After dividing the mesentery, we clipped and cut the vessel, and both ends were further ligated. After these procedures, we safely performed esophagectomy with 3-field lymph node dissection. The postoperative course was uneventful, and the patient was discharged on the 21st postoperative day.

Conclusions

Although there was a firm adhesion in the thoracic cavity, preoperative recognition of the azygos lobe could help in preventing intraoperative injury. Especially, esophageal surgeons are required to deal with the azygos lobe safely to avoid serious intraoperative injury.
Proteomic characterization of esophageal squamous cell carcinoma response to immunotherapy reveals potential therapeutic strategy and predictive biomarkers
Authors: Ma Fahan , Li Yan , Xiang Chan , Wang Bing , Lv Jie , Wei Jinzhi , Qin Zhaoyu , Pu Yan , Li Kai , Teng Haohua , Tan Subei , Feng Jinwen , Shang Zhanxian , Wang Yunzhi , Tian Sha , Du Changsheng , Han Yuchen , Ding Chen
Published: March 2024

Immunotherapy is the first-line therapy for esophageal squamous cell carcinoma (ESCC), yet many patients do not respond due to drug resistance and the lack of reliable predictive markers. We collected 73 ESCC patients (including discovery cohort and validation cohort) without immune thrombocytopenia and undergoing anti-PD1 immunotherapy. Proteomic and phosphoproteomic analysis of 73 ESCC treatment-naive samples by mass spectrometry-based label-free quantification were applied to explore the potential resistant and sensitive mechanisms, and identify predictive markers of ESCC immunotherapy. Comparative analysis found the pathways related to immune and mitochondrial functions were associated with ESCC immunotherapy sensitivity; while platelet activation bioprocess showed negative correlation with CD8+ T cells and related to ESCC immunotherapy non-sensitivity. Finally, we identified 10 ESCC immunotherapy predictive biomarkers with high accuracy (≥ 0.90) to predict the immunotherapeutic response, which was validated in the independent cohort.
Validation of a multiomic model of plasma extracellular vesicle PD-L1 and radiomics for prediction of response to immunotherapy in NSCLC
Authors: de Miguel‑Perez Diego , Ak Murat , Mamindla Priyadarshini , Russo Alessandro , Zenkin Serafettin , Ak Nursima , Peddagangireddy Vishal , Lara‑Mejia Luis , Gunasekaran Muthukumar , Cardona Andres F. , Naing Aung , Hirsch Fred R. , Arrieta Oscar , Colen Rivka R. , Rolfo Christian
Published: March 2024

Background

Immune-checkpoint inhibitors (ICIs) have showed unprecedent efficacy in the treatment of patients with advanced non-small cell lung cancer (NSCLC). However, not all patients manifest clinical benefit due to the lack of reliable predictive biomarkers. We showed preliminary data on the predictive role of the combination of radiomics and plasma extracellular vesicle (EV) PD-L1 to predict durable response to ICIs.

Main body

Here, we validated this model in a prospective cohort of patients receiving ICIs plus chemotherapy and compared it with patients undergoing chemotherapy alone. This multiparametric model showed high sensitivity and specificity at identifying non-responders to ICIs and outperformed tissue PD-L1, being directly correlated with tumor change.

Short conclusion

These findings indicate that the combination of radiomics and EV PD-L1 dynamics is a minimally invasive and promising biomarker for the stratification of patients to receive ICIs.
Trends in pre-hospital volume resuscitation of blunt trauma patients: a 15-year analysis of the British (TARN) and German (TraumaRegister DGU®) National Registries
Authors: Bath M. F. , Schloer J. , Strobel J. , Rea W. , Lefering R. , Maegele M. , De’Ath H. , Perkins Z. B.
Published: March 2024

Introduction

Fluid resuscitation has long been a cornerstone of pre-hospital trauma care, yet its optimal approach remains undetermined. Although a liberal approach to fluid resuscitation has been linked with increased complications, the potential survival benefits of a restrictive approach in blunt trauma patients have not been definitively established. Consequently, equipoise persists regarding the optimal fluid resuscitation strategy in this population.

Methods

We analysed data from the two largest European trauma registries, the UK Trauma Audit and Research Network (TARN) and the German TraumaRegister DGU® (TR-DGU), between 2004 and 2018. All adult blunt trauma patients with an Injury Severity Score > 15 were included. We examined annual trends in pre-hospital fluid resuscitation, admission coagulation function, and mortality rates.

Results

Over the 15-year study period, data from 68,510 patients in the TARN cohort and 82,551 patients in the TR-DGU cohort were analysed. In the TARN cohort, 3.4% patients received pre-hospital crystalloid fluids, with a median volume of 25 ml (20–36 ml) administered. Conversely, in the TR-DGU cohort, 91.1% patients received pre-hospital crystalloid fluids, with a median volume of 756 ml (750–912 ml) administered. Notably, both cohorts demonstrated a consistent year-on-year decrease in the volume of pre-hospital fluid administered, accompanied by improvements in admission coagulation function and reduced mortality rates.

Conclusion

Considerable variability exists in pre-hospital fluid resuscitation strategies for blunt trauma patients. Our data suggest a trend towards reduced pre-hospital fluid administration over time. This trend appears to be associated with improved coagulation function and decreased mortality rates. However, we acknowledge that these outcomes are influenced by multiple factors, including other improvements in pre-hospital care over time. Future research should aim to identify which trauma populations may benefit, be harmed, or remain unaffected by different pre-hospital fluid resuscitation strategies.
Heart rate and breathing effects on attention and memory (HeartBEAM): study protocol for a randomized controlled trial in older adults
Authors: Nashiro Kaoru , Yoo Hyun Joo , Cho Christine , Kim Andy Jeesu , Nasseri Padideh , Min Jungwon , Dahl Martin J. , Mercer Noah , Choupan Jeiran , Choi Paul , Lee Hye Rynn J. , Choi David , Alemu Kalekirstos , Herrera Alexandra Ycaza , Ng Nicole F. , Thayer Julian F. , Mather Mara
Published: March 2024

Background

In healthy people, the “fight-or-flight” sympathetic system is counterbalanced by the “rest-and-digest” parasympathetic system. As we grow older, the parasympathetic system declines as the sympathetic system becomes hyperactive. In our prior heart rate variability biofeedback and emotion regulation (HRV-ER) clinical trial, we found that increasing parasympathetic activity through daily practice of slow-paced breathing significantly decreased plasma amyloid-β (Aβ) in healthy younger and older adults. In healthy adults, higher plasma Aβ is associated with greater risk of Alzheimer’s disease (AD). Our primary goal of this trial is to reproduce and extend our initial findings regarding effects of slow-paced breathing on Aβ. Our secondary objectives are to examine the effects of daily slow-paced breathing on brain structure and the rate of learning.

Methods

Adults aged 50–70 have been randomized to practice one of two breathing protocols twice daily for 9 weeks: (1) “slow-paced breathing condition” involving daily cognitive training followed by slow-paced breathing designed to maximize heart rate oscillations or (2) “random-paced breathing condition” involving daily cognitive training followed by random-paced breathing to avoid increasing heart rate oscillations. The primary outcomes are plasma Aβ40 and Aβ42 levels and plasma Aβ42/40 ratio. The secondary outcomes are brain perivascular space volume, hippocampal volume, and learning rates measured by cognitive training performance. Other pre-registered outcomes include plasma pTau-181/tTau ratio and urine Aβ42. Recruitment began in January 2023. Interventions are ongoing and will be completed by the end of 2023.

Discussion

Our HRV-ER trial was groundbreaking in demonstrating that a behavioral intervention can reduce plasma Aβ levels relative to a randomized control group. We aim to reproduce these findings while testing effects on brain clearance pathways and cognition.

Trial registration

ClinicalTrials.gov NCT05602220. Registered on January 12, 2023.
Impact of climate change on temperature variations and extrinsic incubation period of malaria parasites in Chennai, India: implications for its disease transmission potential
Authors: Kripa P. K. , Thanzeen P. S. , Jaganathasamy Nagaraj , Ravishankaran Sangamithra , Anvikar Anupkumar R. , Eapen Alex
Published: March 2024

Background

The global temperature has significantly risen in the past century. Studies have indicated that higher temperature intensifies malaria transmission in tropical and temperate countries. Temperature fluctuations will have a potential impact on parasite development in the vector Anopheles mosquito.

Methods

Year-long microclimate temperatures were recorded from a malaria-endemic area, Chennai, India, from September 2021 to August 2022. HOBO data loggers were placed in different vector resting sites including indoor and outdoor roof types. Downloaded temperatures were categorised by season, and the mean temperature was compared with data from the same study area recorded from November 2012 to October 2013. The extrinsic incubation period for Plasmodium falciparum and P. vivax was calculated from longitudinal temperatures recorded during both periods. Vector surveillance was also carried out in the area during the summer season.

Results

In general, temperature and daily temperature range (DTR) have increased significantly compared to the 2012–2013 data, especially the DTR of indoor asbestos structures, from 4.30 ℃ to 12.62 ℃ in 2021–2022, unlike the marginal increase observed in thatched and concrete structures. Likewise, the average DTR of outdoor asbestos structures increased from 5.02 ℃ (2012–2013) to 8.76 ℃ (2021–2022) although the increase was marginal in thatched structures and, surprisingly, showed no such changes in concrete structures. The key finding of the extrinsic incubation period (EIP) is that a decreasing trend was observed in 2021–2022 compared to 2012–2013, mainly in indoor asbestos structures from 7.01 to 6.35 days, which negatively correlated with the current observation of an increase in temperature. Vector surveillance undertaken in the summer season revealed the presence of Anopheles breeding in various habitats. Anopheles stephensi could be collected using CDC light traps along with other mosquito species.

Conclusion

The microclimate temperature has increased significantly over the years, and mosquitoes are gradually adapting to this rising temperature. Temperature negatively correlates with the extrinsic incubation period of the parasite. As the temperature increases, the development of the parasite in An. stephensi will be faster because of a decrease in EIP, thus requiring relatively fewer days, posing a risk for disease transmission and a hindrance to malaria elimination efforts.

Graphical Abstract
Synovial sarcoma of the dorsal aspect of the hand: a case report
Authors: Bizhanzadeh Farhad , Heydari Fateme , Rashedi Ronak , Ramezanirad Mohammadhosein , Bahadori Amir Reza
Published: March 2024

Background

Synovial sarcoma is a rare soft tissue sarcoma, with incidences of 0.81/1,000,000 in children and 1.42/1,000,000 in adults. It is most commonly found in soft tissue and rarely in bone. It often has a slow growth pattern and a benign radiologic appearance.

Case presentation

This study reports a case of metacarpal synovial sarcoma occurring in the hand-wrist of a 32-year-old Iranian man presented with the chief complaint of a lump on the dorsal ulnar side of his left hand and wrist. Initially, the first physician suspected the case to be a ganglion cyst. After two months of conservative treatment, the size of the lesion gradually increased. Magnetic resonance imaging (MRI) was performed and after an excisional biopsy and a postoperative histological analysis, the tumor was identified as a synovial sarcoma. The patient underwent a scheduled surgical procedure. Unfortunately, he had poor follow-ups and brought the pathologic results two months later when, the tumor had incredible growth, which makes this presentation rare.

Conclusions

Since early diagnosis can lead to higher survival rates, this report increases doctors' awareness of this extremely malignant tumor that is rarely seen.
SRA-E-ABCO: terminal task offloading for cloud-edge-end environments
Authors: Jiao Shun , Wang Haiyan , Luo Jian
Published: March 2024

The rapid development of the Internet technology along with the emergence of intelligent applications has put forward higher requirements for task offloading. In Cloud-Edge-End (CEE) environments, offloading computing tasks of terminal devices to edge and cloud servers can effectively reduce system delay and alleviate network congestion. Designing a reliable task offloading strategy in CEE environments to meet users’ requirements is a challenging issue. To design an effective offloading strategy, a Service Reliability Analysis and Elite-Artificial Bee Colony Offloading model (SRA-E-ABCO) is presented for cloud-edge-end environments. Specifically, a Service Reliability Analysis (SRA) method is proposed to assist in predicting the offloading necessity of terminal tasks and analyzing the attributes of terminal devices and edge nodes. An Elite Artificial Bee Colony Offloading (E-ABCO) method is also proposed, which optimizes the offloading strategy by combining elite populations with improved fitness formulas, position update formulas, and population initialization methods. Simulation results on real datasets validate the efficient performance of the proposed scheme that not only reduces task offloading delay but also optimize system overhead in comparison to baseline schemes.