bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Diagnosis of Precipitation Type with LightGBM Machine Learning
Authors: Zhuang Haoyu (Richard) , Lehner Flavio , DeGaetano Arthur T.
Published: March 2024

Existing precipitation-type algorithms have difficulty discerning the occurrence of freezing rain and ice pellets. These inherent biases are not only problematic in operational forecasting but also complicate the development of model-based precipitation-type climatologies. To address these issues, this paper introduces a novel light gradient-boosting machine (LightGBM)-based machine learning precipitation-type algorithm that utilizes reanalysis and surface observations. By comparing it with the Bourgouin precipitation-type algorithm as a baseline, we demonstrate that our algorithm improves the critical success index (CSI) for all examined precipitation types. Moreover, when compared with the precipitation-type diagnosis in reanalysis, our algorithm exhibits increased F1 scores for snow, freezing rain, and ice pellets. Subsequently, we utilize the algorithm to compute a freezing-rain climatology over the eastern United States. The resulting climatology pattern aligns well with observations; however, a significant mean bias is observed. We interpret this bias to be influenced by both the algorithm itself and assumptions regarding precipitation processes, which include biases associated with freezing drizzle, precipitation occurrence, and regional synoptic weather patterns. To mitigate the overall bias, we propose increasing the precipitation cutoff from 0.04 to 0.25 mm h−1, as it better reflects the precision of precipitation observations. This adjustment yields a substantial reduction in the overall bias. Finally, given the strong performance of LightGBM in predicting mixed precipitation episodes, we anticipate that the algorithm can be effectively utilized in operational settings and for diagnosing precipitation types in climate model outputs.

Significance Statement

Freezing rain can have significant impacts on transportation and infrastructure, making accurate prediction of precipitation types crucial. In this study, we use a machine learning method known as LightGBM to predict precipitation types. We show that the new algorithm performs better than the existing methods for all precipitation types examined. Additionally, we compute a freezing-rain climatology over the eastern United States. Although the resulting climatology pattern corresponds well to observations, the algorithm overpredicts freezing-rain occurrence. We argue that this bias can be substantially reduced by increasing the precipitation cutoff from 0.04 to 0.25 mm h−1. Overall, this work highlights the potential of the LightGBM algorithm for both weather forecasting and diagnosing precipitation types in climate models.
Multiscale Features and Triggering Mechanisms of the Warm-Sector Heavy Rainfall Accompanied by Warm Shear Along the Yangtze–Huaihe Coastal Regions
Authors: Yu Yiping , Zhang Ling , Song Liuxian , Li Wei , Zhou Lu , Ouyang Lin
Published: March 2024

Using high-resolution hourly precipitation data and ERA5 reanalysis data, this study employs the K-means method to categorize 32 cases of warm-sector heavy rainfall events accompanied by a warm-type shear line (WSWR) along the Yangtze–Huaihe coastal region (YHCR) from April to September during 2010–17. Considering the synoptic system features of WSWR by K means, the result reveals 15 southwest type (SW-type) and 17 south-biased type (S-type) WSWR events. Composite analysis illuminates the distinct dynamic and thermodynamic features of each type. For the SW-type WSWR, the maximum value of water vapor is concentrated around 850 hPa in the lower troposphere. The YHCR is located at the intersection of the exit area of the 850-hPa synoptic low-level jet (LLJ) and the entrance area of the 600-hPa jet. The suction effects, combined with the location of YHCR on the left side of the boundary layer jet (BLJ), facilitate the triggering of local convection. Conversely, the S-type WSWR shows peak water vapor in the boundary layer. Before the onset of WSWR events, a warm, humid tongue indicated by pseudoequivalent potential temperature θse is present in the boundary layer, signified by substantial unstable energy. The BLJ aids mesoscale ascent on its terminus, enhancing convergence along the coastline. The BLJ also channels unstable energy and water vapor to the YHCR, causing significant rainfall. Typical case studies of both types show similar environmental backgrounds. The scale analysis shows mesoscales of dynamic field are crucial in shaping both types of WSWR, while the large-scale and meso-α-scale dynamic field facilitate the transportation of moist and warm airflow.
Observed Subdaily Variations in Air–Sea Turbulent Heat Fluxes under Different Marine Atmospheric Boundary Layer Stability Conditions in the Gulf Stream
Authors: Song Xiangzhou , Xie Xuehan , Yan Yunwei , Xie Shang-Ping
Published: March 2024

Based on data collected from 14 buoys in the Gulf Stream, this study examines how hourly air–sea turbulent heat fluxes vary on subdaily time scales under different boundary layer stability conditions. The annual mean magnitudes of the subdaily variations in latent and sensible heat fluxes at all stations are 40 and 15 W m−2, respectively. Under near-neutral conditions, hourly fluctuations in air–sea humidity and temperature differences are the major drivers of subdaily variations in latent and sensible heat fluxes, respectively. When the boundary layer is stable, on the other hand, wind anomalies play a dominant role in shaping the subdaily variations in latent and sensible heat fluxes. In the context of a convectively unstable boundary layer, wind anomalies exert a strong controlling influence on subdaily variations in latent heat fluxes, whereas subdaily variations in sensible heat fluxes are equally determined by air–sea temperature difference and wind anomalies. The relative contributions by all physical quantities that affect subdaily variations in turbulent heat fluxes are further documented. For near-neutral and unstable boundary layers, the subdaily contributions are O(2) and O(1) W m−2 for latent and sensible heat fluxes, respectively, and they are less than O(1) W m−2 for turbulent heat fluxes under stable conditions.

Significance Statement

High-resolution buoy observations of air–sea variables in the Gulf Stream provide the opportunity to investigate the physical factors that determine subdaily variations in air–sea turbulent heat fluxes. This study addresses two key points. First, the observed subdaily amplitudes of heat fluxes are related to various processes, including wind fields and air–sea thermal effect differences. Second, the global sea surface heat budget is known to not be in near-zero balance and it ranges from several to tens of watts per square meter. Therefore, consideration of the relatively strong influence of subdaily variability in air–sea turbulent heat fluxes could provide a new strategy for solving the global heat budget balance problem.
Art, Intuition, and Identity in Ramón y Cajal
Authors: Hunter Dawn , DeFelipe Javier , Mehta Arpan R. , Conway Bevil R.
Published: March 2024

In the history of neuroscience, Cajal stands tall. Many figures in the late 19th and early 20th centuries made major contributions to neuroscience—Sherrington, Ferrier, Jackson, Holmes, Adrian, and Békésy, to name a few. But in the public mind, Cajal is unique. His application of the Golgi method, with an array of histologic stains, unlocked a wealth of new knowledge on the structure and function of the brain. Here we argue that Cajal’s success should not only be attributed to the importance of his scientific contributions but also to the artistic visual language that he created and to his pioneering self-branding, which exploited methods of the artist, including classical drawing and the new invention of photography. We argue that Cajal created his distinctive visual language and self-branding strategy by interweaving an ostensibly objective research product with an intimately subjective narrative about the brain and himself. His approach is evident in the use of photography, notably self-portraits, which furthered broad engagement initially inspired by his scientific drawings. Through his visual language, Cajal made an impact in art and culture far beyond the bounds of science, which has sustained his scientific legacy.
High-Efficiency Dynamic Scanning Strategy for Powder Bed Fusion by Controlling Temperature Field of the Heat-Affected Zone
Authors: Huang Xiaokang , Tian Xiaoyong , Zhong Qi , He Shunwen , Huo Cunbao , Cao Yi , Tong Zhiqiang , Li Dichen
Published: March 2024

Improvement of fabrication efficiency and part performance was the main challenge for the large-scale powder bed fusion (PBF) process. In this study, a dynamic monitoring and feedback system of powder bed temperature field using an infrared thermal imager has been established and integrated into a four-laser PBF equipment with a working area of 2000 mm × 2000 mm. The heat-affected zone (HAZ) temperature field has been controlled by adjusting the scanning speed dynamically. Simultaneously, the relationship among spot size, HAZ temperature, and part performance has been established. The fluctuation of the HAZ temperature in four-laser scanning areas was decreased from 30.85 ℃ to 17.41 ℃. Thus, the consistency of the sintering performance of the produced large component has been improved. Based on the controllable temperature field, a dynamically adjusting strategy for laser spot size was proposed, by which the fabrication efficiency was improved up to 65.38%. The current research results were of great significance to the further industrial applications of large-scale PBF equipment.
Metagenomic gut microbiome analysis of Japanese patients with multiple chemical sensitivity/idiopathic environmental intolerance
Authors: Watai Kentaro , Suda Wataru , Kurokawa Rina , Sekiya Kiyoshi , Hayashi Hiroaki , Iwata Maki , Nagayama Kisako , Nakamura Yuto , Hamada Yuto , Kamide Yosuke , Fukutomi Yuma , Nakabayashi Takeru , Tanaka Kosei , Kamita Masahiro , Taniguchi Masami , Hattori Masahira
Published: March 2024

Background

Although the pathology of multiple chemical sensitivity (MCS) is unknown, the central nervous system is reportedly involved. The gut microbiota is important in modifying central nervous system diseases. However, the relationship　between the gut microbiota and MCS remains unclear. This study aimed to identify gut microbiota variations associated with MCS using shotgun metagenomic sequencing of fecal samples.

Methods

We prospectively recruited 30 consecutive Japanese female patients with MCS and analyzed their gut microbiomes using shotgun metagenomic sequencing. The data were compared with metagenomic data obtained from 24 age- and sex-matched Japanese healthy controls (HC).

Results

We observed no significant difference in alpha and beta diversity of the gut microbiota between the MCS patients and HC. Focusing on the important changes in the literatures, at the genus level, Streptococcus, Veillonella, and Akkermansia were significantly more abundant in MCS patients than in HC (p < 0.01, p < 0.01, p = 0.01, respectively, fold change = 4.03, 1.53, 2.86, respectively). At the species level, Akkermansia muciniphila was significantly more abundant (p = 0.02, fold change = 3.3) and Faecalibacterium prausnitzii significantly less abundant in MCS patients than in HC (p = 0.03, fold change = 0.53). Functional analysis revealed that xylene and dioxin degradation pathways were significantly enriched (p < 0.01, p = 0.01, respectively, fold change = 1.54, 1.46, respectively), whereas pathways involved in amino acid metabolism and synthesis were significantly depleted in MCS (p < 0.01, fold change = 0.96). Pathways related to antimicrobial resistance, including the two-component system and cationic antimicrobial peptide resistance, were also significantly enriched in MCS (p < 0.01, p < 0.01, respectively, fold change = 1.1, 1.2, respectively).

Conclusions

The gut microbiota of patients with MCS shows dysbiosis and alterations in bacterial functions related to exogenous chemicals and amino acid metabolism and synthesis. These findings may contribute to the further development of treatment for MCS.

Trial registration

This study was registered with the University Hospital Medical Information Clinical Trials Registry as UMIN000031031. The date of first trial registration: 28/01/2018.
“It’s a stressful, trying time for the caretaker”: an interpretive description qualitative study of postoperative transitions in care for older adults with frailty from the perspectives of informal caregivers
Authors: Hladkowicz Emily , Auais Mohammad , Kidd Gurlavine , McIsaac Daniel I , Miller Jordan
Published: March 2024

Background

Older adults with frailty have surgery at a high rate. Informal caregivers often support the postoperative transition in care. Despite the growing need for family and caregiver support for this population, little is known about the experience of providing informal care to older adults with frailty during the postoperative transition in care. The purpose of this study was to explore what is important during a postoperative transition in care for older adults with frailty from the perspective of informal caregivers.

Methods

This was a qualitative study using an interpretive description methodology. Seven informal caregivers to older adults [aged ≥ 65 years with frailty (Clinical Frailty Scale score ≥ 4) who had an inpatient elective surgery] participated in a telephone-based, semi-structured interview. Audio files were transcribed and analyzed using reflexive thematic analysis.

Results

Four themes were constructed: (1) being informed about what to expect after surgery; (2) accessible communication with care providers; (3) homecare resources are needed for the patient; and (4) a support network for the caregivers. Theme 4 included two sub-themes: (a) respite and emotional support and (b) occupational support.

Conclusions

Transitions in care present challenges for informal caregivers of older adults with frailty, who play an important role in successful transitions. Future postoperative transitional care programs should consider making targeted information, accessible communication, and support networks available for caregivers as part of facilitating successful transitions in care.
A noninvasive method for predicting clinically significant prostate cancer using magnetic resonance imaging combined with PRKY promoter methylation level: a machine learning study
Authors: Wang Yufei , Liu Weifeng , Chen Zeyu , Zang Yachen , Xu Lijun , Dai Zheng , Zhou Yibin , Zhu Jin
Published: March 2024

Background

Traditional process for clinically significant prostate cancer (csPCA) diagnosis relies on invasive biopsy and may bring pain and complications. Radiomic features of magnetic resonance imaging MRI and methylation of the PRKY promoter were found to be associated with prostate cancer.

Methods

Fifty-four Patients who underwent prostate biopsy or photoselective vaporization of the prostate (PVP) from 2022 to 2023 were selected for this study, and their clinical data, blood samples and MRI images were obtained before the operation. Methylation level of two PRKY promoter sites, cg05618150 and cg05163709, were tested through bisulfite sequencing PCR (BSP). The PI-RADS score of each patient was estimated and the region of interest (ROI) was delineated by 2 experienced radiologists. After being extracted by a plug-in of 3D-slicer, radiomic features were selected through LASSCO regression and t-test. Selected radiomic features, methylation levels and clinical data were used for model construction through the random forest (RF) algorithm, and the predictive efficiency was analyzed by the area under the receiver operation characteristic (ROC) curve (AUC).

Results

Methylation level of the site, cg05618150, was observed to be associated with prostate cancer, for which the AUC was 0.74. The AUC of T2WI in csPCA prediction was 0.84, which was higher than that of the apparent diffusion coefficient ADC (AUC = 0.81). The model combined with T2WI and clinical data reached an AUC of 0.94. The AUC of the T2WI-clinic-methylation-combined model was 0.97, which was greater than that of the model combined with the PI-RADS score, clinical data and PRKY promoter methylation levels (AUC = 0.86).

Conclusions

The model combining with radiomic features, clinical data and PRKY promoter methylation levels based on machine learning had high predictive efficiency in csPCA diagnosis.
Detection limitations of prion seeding activities in blood samples from patients with sporadic prion disease
Authors: Nonaka Toshiaki , Iwasaki Yasushi , Horiuchi Hiroyuki , Satoh Katsuya
Published: March 2024

Background

Human prion diseases (HPDs) are fatal neurodegenerative disorders characterized by abnormal prion proteins (PrPSc). However, the detection of prion seeding activity in patients with high sensitivity remains challenging. Even though real-time quaking-induced conversion (RT-QuIC) assay is suitable for detecting prion seeding activity in a variety of specimens, it shows lower accuracy when whole blood, blood plasma, and blood-contaminated tissue samples are used. In this study, we developed a novel technology for the in vitro amplification of abnormal prion proteins in HPD to the end of enabling their detection with high sensitivity known as the enhanced quaking-induced conversion (eQuIC) assay.

Methods

Three antibodies were used to develop the novel eQUIC method. Thereafter, SD50 seed activity was analyzed using brain tissue samples from patients with prion disease using the conventional RT-QUIC assay and the novel eQUIC assay. In addition, blood samples from six patients with solitary prion disease were analyzed using the novel eQuIC assay.

Results

The eQuIC assay, involving the use of three types of human monoclonal antibodies, showed approximately 1000-fold higher sensitivity than the original RT-QuIC assay. However, when this assay was used to analyze blood samples from six patients with sporadic human prion disease, no prion activity was detected.

Conclusion

The detection of prion seeding activity in blood samples from patients with sporadic prion disease remains challenging. Thus, the development of alternative methods other than RT-QuIC and eQuIC will be necessary for future research.
ST14 interacts with TMEFF1 and is a predictor of poor prognosis in ovarian cancer
Authors: Nie Xin , Gao Lingling , Zheng Mingjun , Wang Shuang , Wang Caixia , Li Xiao , Liu Ouxuan , Gou Rui , Liu Juanjuan , Lin Bei
Published: March 2024

TMEFF1 is a new protein involved in the physiological functions of the central nervous system, and we previously reported TMEFF1 can promote ovarian cancer. ST14 was determined to be involved in the processes of epidermal differentiation, epithelial cell integrity, and vascular endothelial cell migration, etc. The relationship between ST14 and TMEFF1 in the ovary remains unknown. In this study, we detected the expression of ST14 and TMEFF1 in 130 different ovarian cancer tissues through immunohistochemistry. We determined ST14 and TMEFF1 were highly expressed in ovarian cancer, indicating a higher degree of tumor malignancy and a worse prognosis. Tissues significantly expressing ST14 also highly expressed TMEFF1, and the expression of the two proteins was positively correlated. Consistently, immunofluorescence double staining demonstrated the co-localization of ST14 and TMEFF1 in the same region, and immunoprecipitation confirmed the interaction between ST14 and TMEFF1. TMEFF1 expression was also reduced after knocking down ST14 through Western blot. MTT, wound healing and Transwell assays results determined that knockdown of ST14 inhibited proliferation, migration and invasion of ovarian cancer cells in vitro, but the inhibitory effect was restored after adding TMEFF1 exogenous protein. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways analysis showed that ST14 and its related genes were enriched in the processes of epithelial formation, intercellular adhesion, protein localization, and mitosis regulation. We also clarified the kinase, microRNA, and transcription factor target networks and the impact of genetic mutations on prognosis. Overall, high expression of ST14 and TMEFF1 in ovarian cancer predicts higher tumor malignancy and a worse prognosis. ST14 and TMEFF1 co-localize and interact with each other in ovarian cancer. ST14 can regulate TMEFF1 expression to promote proliferation, migration and invasion of ovarian cancer cells. We speculate that the relationship between ST14 and TMEFF1 in ovarian cancer could become a potential target for anti-cancer therapy.
Identification of BACH1-IT2-miR-4786-Siglec-15 immune suppressive axis in bladder cancer
Authors: Li Xingzhi , Liang Ziji , Pan Jiexin , Zhang Meng , Liu Jinli , Hu Rong , Liao Caiyan
Published: March 2024

The sialic acid binding Ig like lectin 15 (Siglec-15) was previously identified as tumor immune suppressor gene in some human cancers with elusive molecular mechanism to be elucidated. The continuous focus on both clinical and basic biology of bladder cancer leads us to characterize aberrant abundance of BACH1-IT2 associating with stabilization of Siglec-15, which eventually contributes to local immune suppressive microenvironment and therefore tumor advance. This effect was evidently mediated by miR-4786-5p. BACH1-IT2 functions in this scenario as microRNA sponge, and competitively conceals miR-4786 and up-regulates cancer cell surface Siglec-15. The BACH1-IT2-miR-4786-Siglec-15 axis significantly influences activation of immune cell co-culture. In summary, our data highlights the critical involvements of BACH1-IT2 and miR-4786 in immune evasion in bladder cancer, which hints the potential for both therapeutic and prognostic exploitation.
The relationship between tumor-infiltrating neutrophils and clinical outcomes in patients with resectable hepatocellular carcinoma
Authors: Lee Jung Hee , Hong Young Mi
Published: March 2024

Background

The impact of tumor-infiltrating neutrophils (TINs) on clinical outcomes has been reported in various cancer types, but their role in hepatocellular carcinoma (HCC) has not been fully evaluated. The aim of this study was to investigate the prognostic values for TINs in HCC patients undergoing curative resection.

Methods

We assessed immune markers (CD3, CD4, CD8, CD66b) using immunohistochemistry in 115 patients who underwent curative resection for HCC. We analyzed the prognostic values for tumor-infiltrating immune cells, including neutrophils, and other clinicopathological factors.

Results

In the Multivariate Cox analysis of overall survival (OS), alpha-fetoprotein (AFP) ≥ 100 ng/mL (hazard ratio (HR), 2.74, 95% confidence interval (CI), 1.17–6.44; P = 0.021) and Barcelona Clinic Liver Cancer (BCLC) B/C stage (HR, 3.98, 95% CI, 1.68–9.43; P = 0.020) were found to be independent poor prognostic factors in HCC patients undergoing resection. The presence of CD66b+TINs was observed in 66 (57.4%) patients. However, CD66b+TINs were not associated with recurrence-free survival and OS.

Conclusions

Our study identified low CD66b+TINs in resectable HCC, and CD66b+ TINs did not have a significant role for the clinical outcomes of patients undergoing curative resection. The results suggest that TINs may play a role in more advanced stages of HCC.
The role of subjective, interpersonal, and structural social isolation in 12-month and lifetime anxiety disorders
Authors: Nguyen Ann W. , Taylor Harry Owen , Taylor Robert Joseph , Ambroise Alexis Z. , Hamler Tyrone , Qin Weidi , Chatters Linda M.
Published: March 2024

Background

Anxiety disorders are among the most prevalent psychiatric conditions worldwide, and the incidence of anxiety disorders among adults in the U.S. have increased over the last decade. Anxiety disorders can have debilitating effects on multiple areas of functioning and quality of life. Recently, social isolation has emerged as an important public health problem associated with worse health and well-being outcomes. Research on the connection between social isolation and mental health has found that multiple dimensions of social isolation may negatively impact mental health, but few inquiries have focused on the association between social isolation and anxiety. This study examined the relationships between multiple dimensions of social isolation and anxiety disorders in a nationally representative sample of adults aged 18 and older.

Methods

The sample includes 6082 individuals from the National Survey of American Life. This study examined whether three different dimensions of social isolation—subjective, interpersonal, and structural—were associated with 12-month and lifetime anxiety disorders (any anxiety disorder, posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), social anxiety disorder (SAD), and agoraphobia (AG). Logistic regressions were used to test the associations between the three social isolation variables and the anxiety outcomes.

Results

This study found that of the three dimensions of social isolation, subjective isolation was most consistently related to both lifetime and 12-month anxiety disorders. Those who were subjectively isolated had increased odds of meeting criteria for any anxiety disorder, PTSD, GAD, PD, and AG over the past 12 months and throughout their lifetimes. Structural isolation was negatively associated with lifetime and 12-month AG.

Conclusions

Public health approaches should include mental health and primary care providers and need to target social isolation, especially subjective isolation, which may be key in preventing anxiety disorders and the worsening of anxiety disorders. Future public health research is needed on how and in what ways the differing dimensions of social isolation impact mental health.
Effects of Wuxi CDC WeChat official account article features on user engagement in health promotion
Authors: Yin Xinyi , Pan Junxia , Xu Fanfan
Published: March 2024

Objective

To identify the characteristics of subscribers to assess users’ needs and analyze the features of articles published on Wuxi CDC WeChat official account (WOA) to evaluate the effectiveness of health education dissemination and guide future communication strategies.

Methods

Collect data from the WeChat official account (WOA) of the Wuxi Center for Disease Control and Prevention (CDC) to identify factors affecting the effectiveness of health education dissemination as measured by shares and 100% reading completion rate between January 1, 2022, and December 31, 2022. Multivariate logistic regression analysis was utilized to identify influencing features of articles associated with health education dissemination.

Results

By the end of 2022, our account had accumulated 891,170 subscribers, of which, 523,576 were females (58.75%), 349,856 were males (39.3%), mainly located in third-tier cities (82.59%). Age distribution peaked in the 26–35 and 36–45 age groups (43.63% and 30.6%, respectively). A total of 170 articles were included in the analysis. Multivariate logistic regression analysis revealed that articles with a lower word count (OR = 0.999, 95% CI = 0.998 ~ 1), lower picture count (OR = 0.892, 95% CI = 0.828 ~ 0.962), dominated headlines (OR = 2.454, 95% CI = 1.234 ~ 4.879) and thematically focused on Nutrition and food-borne diseases (OR = 5.728, 95% CI = 1.778 ~ 18.458) demonstrated higher engagement, as measured by shares and 100% completion rates.

Conclusions

Our findings suggest that future content should prioritize conciseness, optimize images, and align with subscriber interests, particularly in nutrition and food hygiene. Additionally, maintaining informative yet engaging content formats remains crucial for maximizing reach and impact.
Characteristics, treatments, in-hospital and long-term outcomes among inpatients with acute exacerbation of chronic obstructive pulmonary disease in China: sex differences in a large cohort study
Authors: Zhang Jiarui , Yi Qun , Zhou Chen , Luo Yuanming , Wei Hailong , Ge Huiqing , Liu Huiguo , Zhang Jianchu , Li Xianhua , Xie Xiufang , Pan Pinhua , Yi Mengqiu , Cheng Lina , Zhou Hui , Liu Liang , Aili Adila , Liu Yu , Peng Lige , Pu Jiaqi , Zhou Haixia
Published: March 2024

Background

Data related to the characteristics, treatments and clinical outcomes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients in China are limited, and sex differences are still a neglected topic.

Methods

The patients hospitalized for AECOPD were prospectively enrolled from ten medical centers in China between September 2017 and July 2021. Patients from some centers received follow-up for 3 years. Data regarding the characteristics, treatments and in-hospital and long-term clinical outcomes from male and female AECOPD patients included in the cohort were analyzed and compared.

Results

In total, 14,007 patients with AECOPD were included in the study, and 11,020 (78.7%) were males. Compared with males, female patients were older (74.02 ± 10.79 vs. 71.86 ± 10.23 years, P < 0.001), and had more comorbidities (2.22 ± 1.64 vs. 1.73 ± 1.56, P < 0.001), a higher frequency of altered mental status (5.0% vs. 2.9%, P < 0.001), lower diastolic blood pressure (78.04 ± 12.96 vs. 79.04 ± 12.47 mmHg, P < 0.001). In addition, there were also significant sex differences in a range of laboratory and radiographic findings. Females were more likely to receive antibiotics, high levels of respiratory support and ICU admission than males. The in-hospital and 3-year mortality were not significantly different between males and females (1.4% vs. 1.5%, P = 0.711; 35.3% vs. 31.4%, P = 0.058), while female smokers with AECOPD had higher in-hospital mortality than male smokers (3.3% vs. 1.2%, P = 0.002) and male smokers exhibited a trend toward higher 3-year mortality compared to female smokers (40.7% vs. 33.1%, P = 0.146).

Conclusions

In AECOPD inpatients, females and males had similar in-hospital and long-term survival despite some sex differences in clinical characteristics and treatments, but female smokers had significantly worse in-hospital outcomes than male smokers.

Clinical Trial Registration

Retrospectively registered, registration number is ChiCTR2100044625, date of registration 21/03/2021. URL: http://www.chictr.org.cn/showproj.aspx?proj=121626.
Survival and clinicopathological significance of B7-H3 in bladder cancer: a systematic review and meta-analysis
Authors: sun Haohao , Gao Fei , Liu Yuan , Shao Jianfeng
Published: March 2024

Background

B7-H3 has been implicated in clinical pathological features and prognosis across various cancer types, suggesting its potential as a cancer biomarker. Nevertheless, consensus remains elusive regarding its clinical-pathological and prognostic significance in bladder cancer. To address this gap, we conducted a systematic review and meta-analysis.

Methods

We systematically searched PubMed, Embase, Web of Science, Cochrane, and CNKI databases from their inception up to October 6, 2022. We evaluated the literature’s quality using the Newcastle-Ottawa Scale. We performed meta-analysis using Review Manager 5.3 and STATA 12.0, synthesizing data and calculating odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence intervals (CIs).

Results

After applying eligibility criteria and conducting assessments, we included data from 8 studies, encompassing 1622 bladder cancer patients. Bladder tumor tissues exhibited significantly elevated B7-H3 protein expression compared to normal bladder tissues. Elevated B7-H3 expression was notably associated with patient age, tumor infiltration, and recurrence in bladder cancer. However, no significant correlations were observed with other clinical characteristics. Our pooled HR analysis indicated no significant association between B7-H3 expression and overall survival in bladder cancer patients.

Conclusion

Our meta-analysis unveils the complex role of B7-H3 in bladder cancer progression. It appears to be directly involved in tumor infiltration and recurrence but cannot definitively serve as a prognostic biomarker for bladder cancer. To validate these findings, further well-designed studies, encompassing larger sample sizes and diverse racial backgrounds, are warranted.

PROSPERO registration

No. CRD42022364688.
Optimizing the Maastricht Work-Related Support intervention in clinical patient care: the value of integrating action research into intervention mapping
Authors: Butink Maarten , Hooper Shari , Boonen Annelies , Baadjou Vera , Boymans Tim , Pierik Marieke , de Rijk Angelique
Published: March 2024

Background

Healthcare professionals (HCPs) are increasingly recommended to play an important role in supporting people with chronic disease in work participation. An intervention for HCPs to provide work-related support to their patients in clinical care was developed with intervention mapping (Maastricht Work-Related Support; Maastricht WRS). Action research proposes ‘combining research and practice’, which allows us to incorporate experiences of HCPs while implementing and to realize intervention’s full potential. Therefore, the aim of this study is to explore, by integrating action research into an intervention mapping approach, how experiences of HCPs with early implementation can be used to optimize the Maastricht WRS in clinical care.

Methods

Semi-structured interviews were held with nine HCPs (response rate 82%), involved in care for people with inflammatory arthritis, knee problems or inflammatory bowel disease. Some of them were not yet trained in the Maastricht WRS while others had received the training and were providing the Maastricht WRS.

Results

All participants regarded WRS an important part of clinical care. Untrained HCPs indicated a lack of knowledge and skills in providing the Maastricht WRS, and a need for tools. Trained HCPs were satisfied with the training and tools, but stressed that practical limitations hindered providing the Maastricht WRS. Action research showed that the intervention meets the needs of HCPs, but need some optimizations: (1) organizing ‘intervision’ for HCPs, (2) inform and activate patients to discuss work with their HCP, (3) update initial tools and (4) including patients’ work status in the electronic patient system.

Conclusions

Action research integrated into intervention mapping proved to improve the Maastricht WRS intervention. By involving HCPs, the intervention could be optimized to provide to support people with chronic diseases in clinical care in healthy and sustainable work participation.
Variables associated with antibiotic treatment tolerance in patients with Mycobacterium avium complex pulmonary disease
Authors: Marmor Meghan , Sharifi Husham , Jacobs Susan , Fazeli Kiana , Ruoss Stephen
Published: March 2024

Background

Treatment of Mycobacterium avium complex pulmonary disease (MAC-PD) involves prolonged courses of multiple antibiotics that are variably tolerated and commonly cause adverse drug reactions (ADR). The purpose of this retrospective, single-center study was to identify demographic and disease-related variables associated with significant ADRs among patients treated with antibiotics against MAC-PD.

Methods

We reviewed all patients treated with antibiotic therapy for MAC-PD at a single center from 2000 to 2021. Patients were included if they met diagnostic criteria for MAC-PD, were prescribed targeted antibiotic therapy for any length of time and had their treatment course documented in their health record. We compared patients who completed antibiotics as originally prescribed (tolerant) with those whose antibiotic treatment course was modified or terminated secondary to an ADR (intolerant).

Results

Over the study period, 235 patients were prescribed antibiotic treatment with their clinical course documented in our center’s electronic health record, and 246 treatment courses were analyzed. One hundred forty-three (57%) tolerated therapy versus 108 (43%) experienced ADRs. Among the 108 intolerant courses, 67 (63%) required treatment modification and 49 (46%) required premature treatment termination. Treatment intolerance was associated more frequently with smear positive sputum cultures (34% vs. 20%, p = 0.009), a higher Charlson Comorbidity Index (CCI) (4 vs. 6, p = 0.007), and existing liver disease (7% vs. 1%, p = 0.03). There was no between-group difference in BMI (21 vs. 22), fibrocavitary disease (24 vs. 19%), or macrolide sensitivity (94 vs. 80%). The use of daily therapy was not associated with intolerance (77 vs. 79%). Intolerant patients were more likely to be culture positive after 6 months of treatment (44 vs. 25%).

Conclusions

Patients prescribed antibiotic therapy for MAC-PD are more likely to experience ADRs if they have smear positive sputum cultures at diagnosis, a higher CCI, or existing liver disease. Our study’s rate of early treatment cessation due to ADR’s was similar to that of other studies (20%) but is the first of its kind to evaluate patient and disease factors associated with ADR’s. A systematic approach to classifying and addressing ADRs for patients undergoing treatment for MAC-PD is an area for further investigation.
Underlying mechanisms and cardioprotective effects of SGLT2i and GLP-1Ra: insights from cardiovascular magnetic resonance
Authors: Cersosimo Angelica , Salerno Nadia , Sabatino Jolanda , Scatteia Alessandra , Bisaccia Giandomenico , De Rosa Salvatore , Dellegrottaglie Santo , Bucciarelli-Ducci Chiara , Torella Daniele , Leo Isabella
Published: March 2024

Originally designed as anti-hyperglycemic drugs, Glucagon-Like Peptide-1 receptor agonists (GLP-1Ra) and Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated protective cardiovascular effects, with significant impact on cardiovascular morbidity and mortality. Despite several mechanisms have been proposed, the exact pathophysiology behind these effects is not yet fully understood. Cardiovascular imaging is key for the evaluation of diabetic patients, with an established role from the identification of early subclinical changes to long-term follow up and prognostic assessment. Among the different imaging modalities, CMR may have a key-role being the gold standard for volumes and function assessment and having the unique ability to provide tissue characterization. Novel techniques are also implementing the possibility to evaluate cardiac metabolism through CMR and thereby further increasing the potential role of the modality in this context. Aim of this paper is to provide a comprehensive review of changes in CMR parameters and novel CMR techniques applied in both pre-clinical and clinical studies evaluating the effects of SGLT2i and GLP-1Ra, and their potential role in better understanding the underlying CV mechanisms of these drugs.
Sex differences in the relationship between serum total bilirubin and risk of incident metabolic syndrome in community-dwelling adults: Propensity score analysis using longitudinal cohort data over 16 years
Authors: Kim Ae Hee , Son Da-Hye , Moon Mid-Eum , Jeon Soyoung , Lee Hye Sun , Lee Yong-Jae
Published: March 2024

Background

Research on identifiable risks for metabolic syndrome (MetS) is ongoing, and growing evidence suggests that bilirubin is a potent antioxidant and cytoprotective agent against MetS. However, there have been conflicting results on the association between bilirubin and MetS. Our study aimed to validate the association by separately stratifying data for men and women in a longitudinal prospective study.

Methods

Data were derived from the Korean Genome Epidemiology Study provided by the Korea Centers for Disease Control and Prevention. Data from 5,185 adults aged 40–69 years (3,089 men and 2,096 women) without MetS were analyzed. The participants were divided according to sex-specific quartiles of serum total bilirubin levels and followed up biennially for 16 years (until 2018). The log-rank test was used for obtaining the Kaplan-Meier curves of cumulative incidence of MetS according to sex-specific serum total bilirubin quartiles, and the hazard ratios (HRs) with 95% confidence intervals (CIs) for incident metabolic syndrome were analyzed with a multiple Cox proportional hazard regression analysis model, after propensity score matching for removing differences at baseline.

Results

With increasing serum total bilirubin quartiles, the incidence rate per 1000 person-years proportionally decreased in both men and women. After propensity score matching and adjusting for confounding variables, the HRs (95% CIs) for MetS of the highest quartile in reference to the lowest quartile were 1.00 (0.80–1.24) for men and 0.80 (0.65–0.99) for women. Higher quartiles of serum total bilirubin showed significantly lower cumulative incidence of MetS in women (log-rank test p = 0.009), but not in men (log-rank test p = 0.285).

Conclusion

Serum total bilirubin levels were significantly inversely associated with MetS in women, but there was no significant association observed in men. Sex differences in the effects of serum total bilirubin should be noted when predicting incident MetS by sex in clinical settings.
First report of natural infection of Anopheles gambiae s.s. and Anopheles coluzzii by Wolbachia and Microsporidia in Benin: a cross-sectional study
Authors: Ahouandjinou Minassou Juvénal , Sovi Arthur , Sidick Aboubakar , Sewadé Wilfried , Koukpo Come Zinsou , Chitou Saïd , Towakinou Linda , Adjottin Bruno , Hougbe Steve , Tokponnon Filémon , Padonou Germain Gil , Akogbéto Martin , Messenger Louisa A. , Ossè Razaki A.
Published: March 2024

Background

Recently, bacterial endosymbiont, including Wolbachia and Microsporidia were found to limit the infection of Anopheles mosquitoes with Plasmodium falciparum. This study aimed to investigate the natural presence of key transmission-blocking endosymbionts in Anopheles gambiae and Anopheles coluzzii in Southern Benin.

Methods

The present study was conducted in seven communes (Cotonou, Porto-Novo, Aguégués, Ifangni, Pobè Athiémé, and Grand-Popo) of Southern Benin. Anopheles were collected using indoor/outdoor Human Landing Catches (HLCs) and Pyrethrum Spray Catches (PSCs). Following morphological identification, PCR was used to identify An. gambiae sensu lato (s.l.) to species level and to screen for the presence of both Wolbachia and Microsporidia. Plasmodium falciparum sporozoite infection was also assessed using ELISA.

Results

Overall, species composition in An. gambiae s.l. was 53.7% An. coluzzii, while the remainder was An. gambiae sensu stricto (s.s.). Combined data of the two sampling techniques revealed a mean infection prevalence with Wolbachia of 5.1% (95% CI 0.90–18.6) and 1.3% (95% CI 0.07–7.8) in An. gambiae s.s. and An. coluzzii, respectively. The mean infection prevalence with Microsporidia was 41.0% (95% CI 25.9–57.8) for An. gambiae s.s. and 57.0% (95% CI 45.4–67.9) for An. coluzzii. Wolbachia was only observed in Ifangni, Pobè, and Cotonou, while Microsporidia was detected in all study communes. Aggregated data for HLCs and PSCs showed a sporozoite rate (SR) of 0.80% (95% CI 0.09–2.87) and 0.69% (95% CI 0.09–2.87) for An. gambiae and An. coluzzii, respectively, with a mean of 0.74% (95% CI 0.20–1.90). Of the four individual mosquitoes which harboured P. falciparum, none were also infected with Wolbachia and one contained Microsporidia.

Conclusions

The present study is the first report of natural infections of field-collected An. gambiae s.l. populations from Benin with Wolbachia and Microsporidia. Sustained efforts should be made to widen the spectrum of bacteria identified in mosquitoes, with the potential to develop endosymbiont-based control tools; such interventions could be the game-changer in the control of malaria and arboviral disease transmission.
A versatile engineered extracellular vesicle platform simultaneously targeting and eliminating senescent stromal cells and tumor cells to promote tumor regression
Authors: Gong Liangzhi , Chen Zhengsheng , Feng Kai , Luo Lei , Zhang Juntao , Yuan Ji , Ren Yajing , Wang Yang , Zheng Xianyou , Li Qing
Published: March 2024

Chemotherapy is an important therapeutic approach for malignant tumors for it triggers apoptosis of cancer cells. However, chemotherapy also induces senescence of stromal cells in the tumor microenvironment to promote tumor progression. Strategies aimed at killing tumor cells while simultaneously eliminating senescent stromal cells represent an effective approach to cancer treatment. Here, we developed an engineered Src-siRNA delivery system based on small extracellular vesicles (sEVs) to simultaneously eliminate senescent stromal cells and tumor cells for cancer therapy. The DSPE-PEG-modified urokinase plasminogen activator (uPA) peptide was anchored to the membranes of induced mesenchymal stem cell-derived sEVs (uPA-sEVs), and Src siRNA was loaded into the uPA-sEVs by electroporation (uPA-sEVs-siSrc). The engineered uPA-sEVs-siSrc retained the basic sEVs properties and protected against siSrc degradation. uPA peptide modification enhanced the sEVs with the ability to simultaneously target doxorubicin-induced senescent stromal cells and tumor cells. Src silencing by uPA-sEVs-siSrc induced apoptosis of both senescent stromal cells and tumor cells. The uPA-sEVs-siSrc displayed preferential tumor accumulation and effectively inhibited tumor growth in a tumor xenograft model. Furthermore, uPA-sEVs-siSrc in combination with doxorubicin significantly reduced the senescence burden and enhanced the therapeutic efficacy of chemotherapy. Taken together, uPA-sEVs-siSrc may serve as a promising therapy to kill two birds with one stone, not only killing tumor cells to achieve remarkable antitumor effect, but also eliminating senescent cells to enhance the efficacy of chemotherapeutic agent in tumor regression.

Graphical Abstract
Genetically engineered membrane-based nanoengagers for immunotherapy of pancreatic cancer
Authors: Zhang Haoqi , Li Yuanke , Kang Helong , Lan Jingping , Hou Lin , Chen Zhengbang , Li Fan , Liu Yanqin , Zhao Jiliang , Li Na , Wan Yajuan , Zhu Yiping , Zhao Zhen , Zhang Hongkai , Zhuang Jie , Huang Xinglu
Published: March 2024

Modulating macrophages presents a promising avenue in tumor immunotherapy. However, tumor cells have evolved mechanisms to evade macrophage activation and phagocytosis. Herein, we introduced a bispecific antibody-based nanoengager to facilitate the recognition and phagocytosis of tumor cells by macrophages. Specifically, we genetically engineered two single chain variable fragments (scFv) onto cell membrane: anti-CD40 scFv for engaging with macrophages and anti-Claudin18.2 (CLDN18.2) scFv for interacting with tumor cells. These nanoengagers were further constructed by coating scFv-anchored membrane into PLGA nanoparticle core. Our developed nanoengagers significantly boosted immune responses, including increased recognition and phagocytosis of tumor cells by macrophages, enhanced activation and antigen presentation, and elevated cytotoxic T lymphocyte activity. These combined benefits resulted in enhancing antitumor efficacy against highly aggressive “cold” pancreatic cancer. Overall, this study offers a versatile nanoengager design for immunotherapy, achieved through genetically engineering to incorporate antibody-anchored membrane.