bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extremes of both weight gain and weight loss are associated with increased incidence of heart failure and cardiovascular death: evidence from the CANVAS Program and CREDENCE
Authors: Ferrannini Giulia , Pollock Carol , Natali Andrea , Yavin Yshai , Mahaffey Kenneth W. , Ferrannini Ele 
Published: April 2023

Abstract
Background
Obesity is an independent risk factor for cardiovascular disease (CVD) in patients with type 2 diabetes (T2D). However, it is not known to what extent weight fluctuations might be associated with adverse outcomes. We aimed at assessing the associations between extreme weight changes and cardiovascular outcomes in two large randomised controlled trials of canagliflozin in patients with T2D and high cardiovascular (CV) risk.

Methods
In the study populations of the CANVAS Program and CREDENCE trials, weight change was evaluated between randomization and week 52–78, defining subjects in the top 10% of the entire distribution of weight changes as gainers, subjects in the bottom 10% as losers and the remainder as stable. Univariate and multivariate Cox proportional hazards models were used to test the associations between weight changes categories, randomised treatment and covariates with heart failure hospitalisation (hHF) and the composite of hHF and CV death.

Results
Median weight gain was 4.5 kg in gainers and median weight loss was 8.5 kg in losers. The clinical phenotype of gainers as well as that of losers were similar to that of stable subjects. Weight change within each category was only slightly larger with canagliflozin than placebo. In both trials, gainers and losers had a higher risk of hHF and of hHF/CV death compared with stable at univariate analysis. In CANVAS, this association was still significant by multivariate analysis for hHF/CV death in both gainers and losers vs. stable (hazard ratio – HR 1.61 [95% confidence interval - CI: 1.20–2.16] and 1.53 [95% CI 1.14–2.03] respectively). Results were similar in CREDENCE for gainers vs. stable (adjusted HR for hHF/CV death 1.62 [95% CI 1.19–2.16])

Conclusions
Extremes of weight gain or loss were independently associated with a higher risk of the composite of hHF and CV death. In patients with T2D and high CV risk, large changes in body weight should be carefully assessed in view of individualised management.

Trials registration
CANVAS ClinicalTrials.gov number: NCT01032629. CREDENCE ClinicalTrials.gov number: NCT02065791
Serum triglyceride glucose index is a valuable predictor for visceral obesity in patients with type 2 diabetes: a cross-sectional study
Authors: Yang Qing , Xu Huichao , Zhang Hongli , Li Yanying , Chen Shuxiong , He Dongye , Yang Guangzhi , Ban Bo , Zhang Mei , Liu Fupeng 
Published: April 2023

Abstract
Background
Since the triglyceride glucose (TyG) index can reflect insulin resistance, it has been proven to be an efficient predictor of glycolipid-metabolism-related diseases. Therefore, this study aimed to investigate the predictive value of the TyG index for visceral obesity (VO) and body fat distribution in patients with type 2 diabetes mellitus (T2DM).

Methods
Abdominal adipose tissue characteristics in patients with T2DM, including visceral adipose area (VAA), subcutaneous adipose area (SAA), VAA-to-SAA ratio (VSR), visceral adipose density (VAD), and subcutaneous adipose density (SAD), were obtained through analyses of computed tomography images at the lumbar 2/3 level. VO was diagnosed according to the VAA (> 142 cm2 for males and > 115 cm2 for females). Logistic regression was performed to identify independent factors of VO, and receiver operating characteristic (ROC) curves were used to compare the diagnostic performance according to the area under the ROC curve (AUC).

Results
A total of 976 patients were included in this study. VO patients showed significantly higher TyG values than non-VO patients in males (9.74 vs. 8.88) and females (9.59 vs. 9.01). The TyG index showed significant positive correlations with VAA, SAA, and VSR and negative correlations with VAD and SAD. The TyG index was an independent factor for VO in both males (odds ratio [OR] = 2.997) and females (OR = 2.233). The TyG index ranked second to body mass index (BMI) for predicting VO in male (AUC = 0.770) and female patients (AUC = 0.720). Patients with higher BMI and TyG index values showed a significantly higher risk of VO than the other patients. TyG-BMI, the combination index of TyG and BMI, showed significantly higher predictive power than BMI for VO in male patients (AUC = 0.879 and 0.835, respectively) but showed no significance when compared with BMI in female patients (AUC = 0.865 and 0.835, respectively).

Conclusions
. TyG is a comprehensive indicator of adipose volume, density, and distribution in patients with T2DM and is a valuable predictor for VO in combination with anthropometric indices, such as BMI.
Circulating biosignatures in multiple myeloma and their role in multidrug resistance
Authors: Krishnan S. Rajeev , Bebawy M. 
Published: April 2023

AbstractA major obstacle to chemotherapeutic success in cancer treatment is the development of drug resistance. This occurs when a tumour fails to reduce in size after treatment or when there is clinical relapse after an initial positive response to treatment. A unique and serious type of resistance is multidrug resistance (MDR). MDR causes the simultaneous cross resistance to unrelated drugs used in chemotherapy. MDR can be acquired through genetic alterations following drug exposure, or as discovered by us, through alternative pathways mediated by the transfer of functional MDR proteins and nucleic acids by extracellular vesicles (M Bebawy V Combes E Lee R Jaiswal J Gong A Bonhoure GE Grau, 23 9 1643 1649, 2009).Multiple myeloma is an incurable cancer of bone marrow plasma cells. Treatment involves high dose combination chemotherapy and patient response is unpredictable and variable due to the presence of multisite clonal tumour infiltrates. This clonal heterogeneity can contribute to the development of MDR. There is currently no approved clinical test for the minimally invasive testing of MDR in myeloma.Extracellular vesicles comprise a group of heterogeneous cell-derived membranous structures which include; exosomes, microparticles (microvesicles), migrasomes and apoptotic bodies. Extracellular vesicles serve an important role in cellular communication through the intercellular transfer of cellular protein, nucleic acid and lipid cargo. Of these, microparticles (MPs) originate from the cell plasma membrane and vary in size from 0.1-1um. We have previously shown that MPs confer MDR through the transfer of resistance proteins and nucleic acids. A test for the early detection of MDR would benefit clinical decision making, improve survival and support rational drug use. This review focuses on microparticles as novel clinical biomarkers for the detection of MDR in Myeloma and discusses their role in the therapeutic management of the disease.
The application of extracellular vesicles in colorectal cancer metastasis and drug resistance: recent advances and trends
Authors: Xiong Linjin , Wei Yumeng , Jia Qiang , Chen Jinglin , Chen Tao , Yuan Jiyuan , Pi Chao , Liu Huiyang , Tang Jia , Yin Suyu , Zuo Ying , Zhang Xiaomei , Liu Furong , Yang Hongru , Zhao Ling 
Published: April 2023

AbstractColorectal cancer (CRC) has high incidence and mortality rates and is one of the most common cancers of the digestive tract worldwide. Metastasis and drug resistance are the main causes of cancer treatment failure. Studies have recently suggested extracellular vesicles (EVs) as a novel mechanism for intercellular communication. They are vesicular particles, which are secreted and released into biological fluids, such as blood, urine, milk, etc., by a variety of cells and carry numerous biologically active molecules, including proteins, nucleic acids, lipids, metabolites, etc. EVs play a crucial part in the metastasis and drug resistance of CRC by delivering cargo to recipient cells and modulating their behavior. An in-depth exploration of EVs might facilitate a comprehensive understanding of the biological behavior of CRC metastasis and drug resistance, which might provide a basis for developing therapeutic strategies. Therefore, considering the specific biological properties of EVs, researchers have attempted to explore their potential as next-generation delivery systems. On the other hand, EVs have also been demonstrated as biomarkers for the prediction, diagnosis, and presumed prognosis of CRC. This review focuses on the role of EVs in regulating the metastasis and chemoresistance of CRC. Moreover, the clinical applications of EVs are also discussed.Graphical Abstract
Anaplastic lymphoma kinase expression in PDGFRA-mutated gastrointestinal stromal tumors probably correlates with poor prognosis
Authors: Wu Ying , Gao Beibei , Xia Qin , Zhu Yili , Wang Na , Chang Xiaona , Huang Bo , Luo Danju , Zhang Jiwei , Zhang Peng , Shi Heshui , Fan Jun , Nie Xiu 
Published: April 2023

Abstract
Background
Anaplastic lymphoma kinase (ALK) overexpression and gene alterations have been detected in several mesenchymal tumors, with significant implications for diagnosis, therapy and prognosis. However, few studies have investigated the correlation between ALK expression status and clinicopathological characteristics in patients with gastrointestinal stromal tumors (GISTs).

Methods
A total of 506 GIST patients were enrolled. Sanger sequencing was employed to detect c-KIT and PDGFRA gene mutations. The tissue microarray (TMA) technique and immunohistochemistry were employed to identify the ALK (clone: 1A4 and D5F3) expression status in the tumor tissues. The ALK gene variants of IHC-positive cases were analyzed by fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS). The clinicopathological data were analyzed using SPSS Statistics 26.0.

Results
Among the 506 GIST patients, the c-KIT mutation accounted for 84.2% (426/506), followed by PDGFRA mutation (10.3%, 52/506), while the wild-type accounted for the least (5.5%, 28/506). ALK-positive expression was detected in PDGFRA-mutant GISTs (7.7%, 4/52) but negative for c-KIT-mutant or wild-type GISTs by IHC. Four ALK IHC-positive patients were all male. The tumors all occurred outside the stomach. The predominant patterns of growth were epithelioid (2/4), spindle (1/4), and mixed type (1/4). They were all identified as high-risk classification according to the National Institutes of Health (NIH) classification. Aberrant ALK mutations were not identified by DNA-based NGS except in one of the 4 cases with amplification by FISH.

Conclusion
Our study revealed 7.7% (4/52) of ALK expression in PDGFRA-mutant GISTs, indicating that molecular tests were required to rule out the possibility of PDGFRA-mutant GISTs when encountering ALK-positive mesenchymal tumors with CD117-negative or weakly positive in immunohistochemical staining.
Time to postpartum family planning initiation and its predictors among mothers coming for first measles vaccination at Family Guidance Association of Ethiopia, Dessie Model Clinic, Northeast Ethiopia: cox-regression model
Authors: Adane Bezawit , Addisu Elsabeth , Yalew Melaku , Damtie Yitayish , Arefaynie Mastewal , Zewdie Segenet , Wasihun Yitbarek , Kefale Bereket 
Published: April 2023

AbstractBackgroundTiming of initiation of family planning is an important determinant for the health status of the mother and her child. One-fourths of mothers in developing countries who wanted to space or limit their children were not using family planning methods at right time after delivery. Despite, the existence of many literatures about postpartum family planning, the timing of it is not yet studied. Thus, this study aimed to assess time to postpartum family planning and its predictors among mothers coming for first measles vaccination in Dessie city, Northeast Ethiopia.MethodsAn institutional-based retrospective follow-up study was conducted among mothers coming for infant vaccination at Family Guidance Association of Ethiopia, Dessie Model Clinic in Dessie City. A systematic sampling technique was used. The data were entered and analyzed using Epi Data version 3.1 and STATA version 14.0, respectively. Kaplan–Meier and Cox regression model were used to test the time and predictors of postpartum family planning initiation. Adjusted hazard ratio with 95% CI was used to test the strength of association at a p-value of 0.05.ResultsThe rate of postpartum FP initiation was 0.6% with 95% CI  (0.0056, 0.0069). Keeping the effect of confounder constant, age of the women 20–24 [AHR = 2.63, 95% CI (1.65,4.19)], 25–29 [AHR = 3.66, 95% CI (2.35,5.73)], 30–34 [AHR = 2.79, 95% CI (1.75,4.46)], getting family planning counseling [AHR = 1.78, 95% CI (1.26, 2.52)], want more child [AHR = 0.47, 95% CI (0.34, 0.66)], having history of abortion [AHR = 0.54, 95% CI (0.36,0.81)] and wanted last pregnancy [AHR = 0.69, 95% CI (0.49, 0.97) were significantly associated with postpartum family planning initiation.ConclusionsAge, history of abortion, counseling about family planning, the status of last pregnancy and want more child were significantly associated with postpartum family planning use. Continuous emphasis should be given for health care providers to encourage their counseling services for their customers at different age groups with special attention given for elders.
A high quality, high molecular weight DNA extraction method for PacBio HiFi genome sequencing of recalcitrant plants
Authors: Nishii Kanae , Möller Michael , Foster Robert G. , Forrest Laura L. , Kelso Nathan , Barber Sadie , Howard Caroline , Hart Michelle L. 
Published: April 2023

Abstract
Background
PacBio HiFi sequencing provides highly accurate long-read sequencing datasets which are of great advantage for whole genome sequencing projects. One limitation of the method is the requirement for high quality, high molecular weight input DNA. This can be particularly challenging for plants that frequently contain common and species-specific secondary metabolites, which often interfere with downstream processes. Cape Primroses (genus Streptocarpus), are some of these recalcitrant plants and are selected here as material to develop a high quality, high molecular weight DNA extraction protocol for long read genome sequencing.

Results
We developed a DNA extraction method for PacBio HiFi sequencing for Streptocarpus grandis and Streptocarpus kentaniensis. A CTAB lysis buffer was employed to avoid guanidine, and the traditional chloroform and phenol purification steps were replaced with pre-lysis sample washes. Best cells/nucleus lysis was achieved with 4 h at 58 °C. The obtained high quality and high molecular weight DNAs were tested in PacBio SMRTBell™ library preparations, which resulted in circular consensus sequencing (CCS) reads from 17 to 27 Gb per cell, and a read length N50 from 14 to 17 kbp. To evaluate the quality of the reads for whole genome sequencing, they were assembled with HiFiasm into draft genomes, with N50 = 49 Mb and 23 Mb, and L50 = 10 and 11. The longest contigs were 95 Mb and 57 Mb respectively, showing good contiguity as these are longer than the theoretical chromosome length (genome size/chromosome number) of 78 Mb and 55 Mb, for S. grandis and S. kentaniensis respectively.

Conclusions
DNA extraction is a critical step towards obtaining a complete genome assembly. Our DNA extraction method here provided the required high quality, high molecular weight DNA for successful standard-input PacBio HiFi library preparation. The contigs from those reads showed a high contiguity, providing a good starting draft assembly towards obtaining a complete genome. The results obtained here were highly promising, and demonstrated that the DNA extraction method developed here is compatible with PacBio HiFi sequencing and suitable for de novo whole genome sequencing projects of plants.
Comparison of outcomes between transcatheter tricuspid valve repair and surgical tricuspid valve replacement or repair in patients with tricuspid insufficiency
Authors: Wang Xiqiang , Ma Yanpeng , Liu Zhongwei , Fan Xiude , Guan Gongchang , Pan Shuo , Wang Junkui , Zhang Yong 
Published: April 2023

Abstract
Background
Tricuspid regurgitation is associated with significant morbidity and mortality, but with limited treatment options. The objective of this study is to compare the demographic characteristics, complications, and outcomes of transcatheter tricuspid valve repair (TTVr) versus surgical tricuspid valve replacement (STVR) or surgical tricuspid valve repair (STVr), using real-world data from the National Inpatient Sample (NIS) database.

Methods and results
Our study analyzed data from the National Inpatient Sample (NIS) database from 2016 to 2018 and identified 92, 86, and 84 patients with tricuspid insufficiency who underwent STVr, STVR, and TTVr, respectively. The mean ages of patients who received STVr, STVR, and TTVr were 65.03 years, 66.3 years, and 71.09 years, respectively, with TTVr patients significantly older than those who received STVr (P < 0.05). Patients who received STVr or STVR had higher mortality rates (8.7% and 3.5%, respectively) compared to those who received TTVr (1.2%). Patients who underwent STVr or STVR were also more likely to experience perioperative complications, including third-degree atrioventricular block (8.7% STVr vs. 1.2% TTVr, P = 0.329; 38.4% STVR vs. 1.2% TTVr, P < 0.05), respiratory failure (5.4% STVr vs. 1.2% TTVr, P = 0.369; 15.1% STVR vs. 1.2% TTVr, P < 0.05), respiratory complications (6.5% STVr vs. 1.2% TTVr, P = 0.372; 19.8% STVR vs. 1.2% TTVr, P < 0.05), acute kidney injury (40.2% STVr vs. 27.4% TTVr, P = 0.367; 34.9% STVR vs. 27.4% TTVr, P = 0.617), and fluid and electrolyte disorders (44.6% STVr vs. 22.6% TTVr, P = 0.1332; 50% STVR vs. 22.6% TTVr, P < 0.05). In addition, the average cost of care and the average length of hospital stay were higher for patients who underwent STVr or STVR than for those who received TTVr (USD$37995 ± 356008.523 STVr vs. USD$198397 ± 188943.082 TTVr, P < 0.05; USD$470948 ± 614177.568 STVR vs. USD$198397 ± 188943.082 TTVr, P < 0.05; 15.4 ± 15.19 STVr vs. 9.6 ± 10.21 days TTVr, P = 0.267; 24.7 ± 28.81 STVR vs. 9.6 ± 10.21 days TTVr, P < 0.05).

Conclusion
TTVr has shown to have favorable outcomes compared to STVr or STVR, but more research and clinical trials are required to help formulate evidence-based guidelines for the role of catheter-based management in tricuspid valve disease.
Sleep quality, anxiety, symptoms of depression, and caregiver burden among those caring for patients with Dravet syndrome: a prospective multicenter study in Germany
Authors: Maltseva Margarita , Schubert-Bast Susanne , Zöllner Johann Philipp , Bast Thomas , Mayer Thomas , von Spiczak Sarah , Ruf Susanne , Trollmann Regina , Wolff Markus , Hornemann Frauke , Klotz Kerstin A. , Jacobs Julia , Kurlemann Gerhard , Neubauer Bernd A. , Polster Tilman , Syrbe Steffen , Bertsche Astrid , Bettendorf Ulrich , Kluger Gerhard , Flege Silke , Rosenow Felix , Kay Lara , Strzelczyk Adam 
Published: April 2023

Abstract
Background
This study measured sleep quality among caregivers of patients with Dravet syndrome (DS) and assessed the impacts of mental health problems and caregiver burden on sleep quality.

Methods
This multicenter, cross-sectional study of patients with DS and their caregivers throughout Germany consisted of a questionnaire and a prospective 4-week diary querying disease characteristics, demographic data, living conditions, nocturnal supervision, and caregivers’ work situations. Sleep quality was assessed using the Pittsburgh Sleeping Quality Index (PSQI). The Hospital Anxiety and Depression Scale (HADS) and the Burden Scale for Family Caregivers (BSFC) were used to measure anxiety, symptoms of depression, and caregiver burden.

Results
Our analysis included 108 questionnaires and 82 four-week diaries. Patients with DS were 49.1% male (n = 53), with a mean age of 13.5 ± 10.0 years. Caregivers were 92.6% (n = 100) female, with a mean age of 44.7 ± 10.6 years. The overall mean PSQI score was 8.7 ± 3.5, with 76.9% of participants (n = 83) scoring 6 or higher, indicating abnormal sleep quality. The HADS for anxiety and depression had overall mean scores of 9.3 ± 4.3 and 7.9 ± 3.7, respectively; 61.8% and 50.9% of participants scored above the cutoff value of 8 for anxiety and depression, respectively. Statistical analyses revealed caregiver anxiety levels and patients’ sleep disturbances as major factors influencing PSQI scores. The overall mean BSFC score of 41.7 ± 11.7 indicates a moderate burden, with 45.3% of caregivers scoring 42 or higher.

Conclusions
Sleep quality is severely affected among caregivers of patients with DS, correlating with anxiety, comorbidities, and patients’ sleep disturbances. A holistic therapeutic approach should be implemented for patients with DS and their caregivers, focusing on the sleep quality and mental health of caregivers.
Trial registration: German Clinical Trials Register (DRKS), DRKS00016967. Registered 27 May 2019, http://www.drks.de/DRKS00016967
Mental health profiles of Finnish adolescents before and after the peak of the COVID-19 pandemic
Authors: Gustafsson Jasmine , Lyyra Nelli , Jasinskaja-Lahti Inga , Simonsen Nina , Lahti Henri , Kulmala Markus , Ojala Kristiina , Paakkari Leena 
Published: April 2023

Abstract
Background
The COVID-19 pandemic has had implications for adolescents’ interpersonal relationships, communication patterns, education, recreational activities and well-being. An understanding of the impact of the pandemic on their mental health is crucial in measures to promote the post-pandemic recovery. Using a person-centered approach, the current study aimed to identify mental health profiles in two cross-sectional samples of Finnish adolescents before and after the peak of the pandemic, and to examine how socio-demographic and psychosocial factors, academic expectations, health literacy, and self-rated health are associated with the emerging profiles.

Methods and findings
Survey data from the Health Behaviour in School-aged Children (HBSC) study conducted in Finland in 2018 (N = 3498, age M = 13.44) and 2022 (N = 3838, age M = 13.21) were analyzed. A four-profile model using cluster analysis was selected for both samples. In Sample 1, the identified profiles were (1) “Good mental health”, (2) “Mixed psychosocial health”, (3) “Somatically challenged”, and (4) “Poor mental health”. In Sample 2, the identified profiles were (1) “Good mental health”, (2) “Mixed psychosomatic health”, (3) “Poor mental health and low loneliness”, and (4) “Poor mental health and high loneliness”. The results of the mixed effect multinomial logistic regression analysis showed that in both samples, being a girl and reporting lower maternal monitoring; lower family, peer, and teacher support; higher intensity of online communication; a less positive home atmosphere and school climate; and poor self-rated health were most strongly linked to belonging to a poorer mental health profile. In addition, in Sample 2, low subjective health literacy was a key factor associated with poorer mental health profiles, and teacher support was more important than before COVID.

Conclusions
The current study stresses the importance of identifying those vulnerable to developing poor mental health. To maximize post-pandemic recovery, the role of schools, especially teacher support and health literacy, along with the factors that remained important over time should be taken into account in public health and health promotion interventions.