bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between serum insulin levels and heart failure-related parameters in patients with type 2 diabetes and heart failure treated with canagliflozin: a post-hoc analysis of the randomized CANDLE trial
Authors: Tanaka Atsushi , Imai Takumi , Shimabukuro Michio , Taguchi Isao , Sezai Akira , Toyoda Shigeru , Watada Hirotaka , Ako Junya , Node Koichi ,   the CANDLE trial investigators
Published: August 2022

Abstract
Background
Insulin resistance and hyperinsulinemia in patients with type 2 diabetes (T2D) are adversely associated with the development and worsening of heart failure (HF). Herein, we sought to investigate the effect of canagliflozin on insulin concentrations and the associations of changes in insulin concentrations with HF-related clinical parameters in patients with T2D and HF.

Methods
This was a post-hoc analysis of the investigator-initiated, multicenter, open-label, randomized, controlled CANDLE trial for patients with T2D and chronic HF (UMIN000017669). The endpoints were the effects of 24 weeks of canagliflozin treatment, relative to glimepiride treatment, on insulin concentrations and the relationship between changes in insulin concentrations and clinical parameters of interest, including New York Heart Association (NYHA) classification. The effects of canagliflozin on those parameters were also analyzed by baseline insulin level.

Results
Among the participants in the CANDLE trial, a total of 129 patients (canagliflozin, n = 64; glimepiride, n = 65) who were non-insulin users with available serum insulin data both at baseline and week 24 were included in this analysis. Overall, the mean age was 69.0 ± 9.4 years; 75% were male; the mean HbA1c was 6.8 ± 0.7%; and the mean left ventricular ejection fraction was 59.0 ± 14.1%, with parameters roughly balanced between treatment groups. Canagliflozin treatment significantly reduced insulin concentrations at week 24 (p < 0.001), and the between-group difference (canagliflozin minus glimepiride) in those changes was − 3.52 mU/L (95% confidence interval, − 4.85 to − 2.19; p < 0.001). Decreases in insulin concentrations, irrespective of baseline insulin level, were significantly associated with improvement in NYHA class in patients treated with canagliflozin.

Conclusion
Our findings suggest that canagliflozin treatment in patients with T2D and HF ameliorated excess insulin overload, contributing to the improvement of clinical HF status.
Trial registration: University Medical Information Network Clinical Trial Registry, number 000017669, Registered on May 25, 2015.
Glucose tolerance and markers of myocardial injury after an acute coronary syndrome: predictive role of the 1-h plus 2-h plasma glucose at the oral glucose tolerance test
Authors: Zywicki Viola , Capozza Paola , Caravelli Paolo , Del Prato Stefano , De Caterina Raffaele 
Published: August 2022

Abstract
Objective
Impaired glucose tolerance (IGT) has been related to adverse cardiovascular outcomes. We investigated the added value of 1-h plasma glucose (PG) at the oral glucose tolerance test (OGTT) in predicting admission and peak cardiac high-sensitivity troponin T (hs-TnT) and NT-proBNP values in IGT patients admitted for an acute coronary syndrome (ACS).

Research design and methods
Among 192 consecutive ACS patients, 109 had Hb1Ac and fasting plasma glucose negative for newly diagnosed diabetes. Upon OGTT performed > 96 h after admission, 88, conventionally diagnosed as IGT, were divided into: “full glucose tolerance” (1-h PG-OGTT < 155 mg/dL and 2-h PG-OGTT < 140 mg/dL, N = 12);”early IGT” (1 h-PG-OGTT ≥ 155 mg/dL and 2-h PG-OGTT < 140 mg/dL, N = 33);”late IGT” (1-h PG-OGTT < 155 mg/dL and 2-h PG-OGTT ≥ 140 mg/dL, N = 8); and “full IGT” (1-h PG-OGTT ≥ 155 mg/dL and 2-h PG-OGTT ≥ 140 mg/dL, N = 35). The 4 groups were compared for cardiac markers.

Results
The first three groups had similar cardiac marker values, but only full IGT patients had significantly higher admission hs-TnT compared with the 3 other groups [median (interquartile range): 911 (245-2976) vs 292 (46-1131), P < 0.001]. Full IGT patients also had higher hs-TnT peak compared with fully glucose tolerant and early IGT patients. Only full IGT patients had longer hospitalization and higher NT-proBNP vs fully glucose tolerant patients (P = 0.005).

Conclusions
Among non-diabetic ACS patients, only those with both 1-h PG ≥ 155 mg/dL and 2-h PG ≥ 140 mg/dL had more severe myocardial injury and longer hospitalization. One-h PG-OGTT importantly contributes to assessing post-ACS cardiac risk.
Mnsod1 promotes the development of Pleurotus ostreatus and enhances the tolerance of mycelia to heat stress
Authors: Hou Ludan , Liu Zongqi , Yan Kexing , Xu Lijing , Chang Mingchang , Meng Junlong 
Published: August 2022

Abstract
Background
Superoxide dismutases (SODs, EC 1.15.1.1) are defense proteins that can be used as sweepers to clear reactive oxygen species (ROS). They have been widely studied in the plant. Intensive research demonstrates that SOD plays an essential role in plants. However, in Pleurotus ostreatus, the function and regulatory pathway of SOD in the growth and development and the abiotic stress response have not been clear.

Results
In this study, three MnSOD-encoding genes of the P. ostreatus CCMSSC00389 strain were cloned and identified. Mnsod1, Mnsod2, and Mnsod3 were interrupted by 3, 7, and 2 introns, and encoded proteins of 204, 220, and 344 amino acids, respectively. By comparing the relative expression of three MnSOD-encoding genes in mycelia, the results showed that the gene with the highest primary expression was Mnsod1. Subsequently, the function of P. ostreatus Mnsod1 was explored by overexpression (OE) and RNA interference (RNAi). The results showed that during the growth and development of P. ostreatus, MnSOD1 protein increased gradually from mycelia to the fruiting body, but decreased in spores. The change of Mnsod1 transcription level was not consistent with the changing trend of MnSOD1 protein. Further studies showed that during primordia formation, the expression of Mnsod1 gradually increased, reaching a peak at 48 h, and the transcription level was 2.05-folds compared to control. H2O2 content progressively accumulated during the formation of primordia, and its change trend was similar to that of Mnsod1 transcription. OE-Mnsod1-1 and OE-Mnsod1-21 strains accelerated the formation of primordia. The results suggested that Mnsod1 may participate in the formation rate of P. ostreatus primordium by regulating the signal molecule H2O2. In addition, OE-Mnsod1-1 and OE-Mnsod1-21 strains shortened the mycelial recovery time after heat stress and improved the tolerance of the strains to 2.5 mM and 5 mM H2O2, which showed that Mnsod1 was involved in the response of P. ostreatus mycelium to heat stress.

Conclusions
This study indicates that Mnsod1 plays an active role in the formation of P. ostreatus primordia and the response to abiotic stress.
Targeting Ras-ERK cascade by bioactive natural products for potential treatment of cancer: an updated overview
Authors: Ali Eunus S. , Akter Shamima , Ramproshad Sarker , Mondal Banani , Riaz Thoufiqul Alam , Islam Muhammad Torequl , Khan Ishaq N. , Docea Anca Oana , Calina Daniela , Sharifi-Rad Javad , Cho William C. 
Published: August 2022

AbstractMAPK (mitogen-activated protein kinase) or ERK (extracellular-signal-regulated kinase) pathway is an important link in the transition from extracellular signals to intracellular responses. Because of genetic and epigenetic changes, signaling cascades are altered in a variety of diseases, including cancer. Extant studies on the homeostatic and pathologic behavior of MAPK signaling have been conducted; however, much remains to be explored in preclinical and clinical research in terms of regulation and action models. MAPK has implications for cancer therapy response, more specifically in response to experimental MAPK suppression, compensatory mechanisms are activated. The current study investigates MAPK as a very complex cell signaling pathway that plays roles in cancer treatment response, cellular normal conduit maintenance, and compensatory pathway activation. Most MAPK inhibitors, unfortunately, cause resistance by activating compensatory feedback loops in tumor cells and tumor microenvironment components. As a result, innovative combinatorial treatments for cancer management must be applied to limit the likelihood of alternate pathway initiation as a possibility for generating novel therapeutics based on incorporation in translational research. We summarize current knowledge about the implications of ERK (MAPK) in cancer, as well as bioactive products from plants, microbial organisms or marine organisms, as well as the correlation with their chemical structures, which modulate this pathway for the treatment of different types of cancer.
Association of physical activity with utilization of long-term care in community-dwelling older adults in Germany: results from the population-based KORA-Age observational study
Authors: Steinbeisser Kathrin , Schwarzkopf Larissa , Schwettmann Lars , Laxy Michael , Grill Eva , Rester Christian , Peters Annette , Seidl Hildegard 
Published: August 2022

Abstract
Background
Physical activity (PA) is a proven strategy to prevent chronic diseases and reduce falls. Furthermore, it improves or at least maintains performance of activities of daily living, and thus fosters an independent lifestyle in older adults. However, evidence on the association of PA with relevant subgroups, such as older adults with utilization of long-term care (LTC), is sparse. This knowledge would be essential for establishing effective, need-based strategies to minimize the burden on healthcare systems due to the increasing need for LTC in old age.

Methods
Data originate from the 2011/12 (t1) baseline assessment and 2016 (t2) follow-up of the population-based Cooperative Health Research in the Region of Augsburg (KORA-)Age study in southern Germany. In 4812 observations of individuals ≥65 years, the association between various types of PA (walking, exercise (i. e., subcategory of PA with the objective to improve or maintain one or more components of physical fitness), walking+exercise) and utilization of LTC (yes/no) was analyzed using generalized estimating equation logistic models. Corresponding models stratified by sex (females: 2499 observations; males: 2313 observations) examined sex-specific associations. Descriptive analyses assessed the proportion of individuals meeting the suggested minimum values in the German National Physical Activity Recommendations for older adults (GNPAR).

Results
All types of PA showed a statistically significant association with non-utilization of LTC in the entire cohort. “Walking+exercise” had the strongest association with non-utilization of LTC in the entire cohort (odds ratio (OR): 0.52, 95% confidence interval (CI): 0.39–0.70) and in males (OR: 0.41, CI: 0.26–0.65), whereas in females it was “exercise” (OR: 0.58; CI: 0.35–0.94). The proportion of individuals meeting the GNPAR was higher among those without utilization of LTC (32.7%) than among those with LTC (11.7%) and group differences were statistically significant (p ≤ 0.05).

Conclusions
The GNPAR are rarely met by older adults. However, doing any type of PA is associated with non-utilization of LTC in community-dwelling older adults. Therefore, older adults should be encouraged to walk or exercise regularly. Furthermore, future PA programs should consider target-groups’ particularities to reach individuals with the highest needs for support.
Sex- and body mass index-specific reference intervals for serum leptin: a population based study in China
Authors: Cheng Jiayu , Luo Yingying , Li Yufeng , Zhang Fang , Zhang Xiuying , Zhou Xianghai , Ji Linong 
Published: August 2022

Abstract
Background
Leptin is a peptide hormone secreted by adipose tissue and is an important determinant of obesity and its complications. The purpose of this study was to establish sex- and body mass index (BMI)-specific reference intervals for serum leptin in a Chinese population and investigate the factors influencing leptin concentrations.

Methods
Fasting serum leptin levels were assayed in 469 men and 773 women from randomly sampled Chinese residents. Blood glucose, insulin, hemoglobin A1c (HbA1c), liver enzymes, blood lipid profiles, creatinine, and uric acid (UA) levels were measured. Pearson’s correlation coefficient and multiple linear regression analyses were used to estimate the relationship between serum leptin level and other variables. The reference intervals were determined by the 2.5th and 97.5th percentiles.

Results
The mean ± standard deviation serum leptin level was much higher in women (20.92 ± 12.96 ng/mL) than in men (6.45 ± 5.53 ng/mL). The reference interval of serum leptin was 0.33–19.85 ng/mL in men and 3.60–54.86 ng/mL in women. The specific reference intervals of serum leptin in men with BMI of 20 to < 25 and 25 to < 27.5 kg/m2 were 0.42–12.32 and 2.17–20.22 ng/ml, respectively. The specific reference intervals of serum leptin in women with BMI of 20 to < 25 and 25 to < 27.5 kg/m2 were 4.11–38.09 and 8.27–48.66 ng/ml, respectively. BMI was significantly correlated with Ln (leptin) both in men (r = 0.698, P < 0.001) and women (r = 0.626, P < 0.001). In multivariate linear regression analysis, serum leptin was correlated with BMI, homeostasis model assessment of insulin resistance (HOMA-IR), UA in women, and plus triglyceride (TG) in men. The variance in serum leptin levels could be partially explained by these variables in both women (adjusted R2 = 0.447) and men (adjusted R2 = 0.552). In participants with leptin levels higher than the reference intervals, significantly higher levels of HOMA-IR, low-density lipoprotein cholesterol (LDL-C), UA, a higher proportion of central obesity (waist circumference [WC] > 90 cm), and metabolic syndrome were found in men, and significantly higher levels of HOMA-IR, UA and a higher proportion of central obesity (WC > 85 cm) were found in women.

Conclusion
This is the first study to establish sex- and BMI-specific reference intervals of leptin for both sexes in a large Chinese population. Serum concentration of leptin was predicted by BMI, HOMA-IR, UA in women, and TG in men.
Follicular dendritic cell sarcoma of gastrointestinal tract with two emerging distinct subtypes: a case report and systemic review
Authors: Gui Hongxing , Chaudhari Jigisha , Mannan Rifat 
Published: August 2022

Abstract
Background
Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm of mesenchymal origin. FDCS of gastrointestinal tract (GI) are exceedingly uncommon.

Case presentation
We report the first case of classic type FDCS in a 34-year-old male with Birt-Hogg-Dubé syndrome, which presented as a mass at the ileo-cecal junction. He received no further treatment after resection and remained disease free for 3.5 years. We further analyze and review the clinical and pathologic findings of 33 cases of GI tract FDCS reported in the literature.

Conclusions
There are two distinct subtypes of FDCS in the GI tract: the classic type occurs in relatively younger patients (mean = 45.3 years) without Epstein-Barr virus (EBV) association, and behaves more aggressively; the inflammatory subtype presents as colonic polypoid tumor in older patients (mean = 60.7 years) and is EBV positive. The clinical outcome in the latter group appears favorable although mortality rate is not necessarily low.
The role of neoadjuvant radiochemotherapy in the management of localized high-grade soft tissue sarcoma
Authors: Kobus Marta , Roohani Siyer , Ehret Felix , Flörcken Anne , Striefler Jana Käthe , Brandes Franziska , Märdian Sven , Rau Daniel , Wittenberg Silvan , Öllinger Robert , Kaul David 
Published: August 2022

Abstract
Background
Standard treatment of soft tissue sarcoma (STS) of the extremities includes limb-sparing surgery combined with pre- or postoperative radiotherapy (RT). The role of perioperative chemotherapy (CTX) remains uncertain. STS patients with high-risk features for local recurrence, distant metastases, and increased mortality may require additional systemic therapy. The objective of this study was to evaluate predictors of outcome regarding local control (LC), overall survival (OS), and freedom from distant metastases (FFDM) in a large single-center cohort of patients suffering from localized high-grade STS (grade 2/3, G2/G3). Special emphasis was put on a subgroup of patients who received combined neoadjuvant radiochemotherapy (RCT).

Methods
Overall, 115 adult STS patients were included in this retrospective study. The median follow-up was 34 months. Twenty-three patients (20.0%) were treated with neoadjuvant RCT, 92 (80.0%) received other therapies (adjuvant RT alone (n = 58); neoadjuvant CTX + adjuvant RT (n = 17); adjuvant RCT (n = 10), neoadjuvant RT alone (n = 7)). To assess potential prognostic factors on LC, OS, and FFDM, univariate (UVA) and multivariable (MVA) Cox proportional hazards models were applied.

Results
UVA showed significantly better LC rates in the neoadjuvant RCT group (p = 0.025), with trends in MVA (p = 0.057). The 3-year LC rate was 89.7% in the neoadjuvant RCT group vs. 75.6% in the "other therapies" group. UVA also showed significantly better OS rates in the neoadjuvant RCT group (p = 0.049), however, this was not confirmed in MVA (p = 0.205), the 3-year OS rate was 85.8% for patients treated with neoadjuvant RCT compared to 73.5% in the "other therapies" group. UVA showed significantly better FFDM rates in (p = 0.018) and a trend towards better FFDM rates in MVA (p = 0.059). The 3-year FFDM rate was 89.7% for patients treated with neoadjuvant RCT compared to 65.9% in the "other therapies" group. In the subgroup of patients with G3 STS, neoadjuvant RCT was a significant positive predictor of LC and FFDM in MVA (p = 0.047, p = 0.027) but not for OS. Overall grade 3 and 4 toxicities were significantly higher (p = 0.019) in the neoadjuvant RCT group and occurred in 73.9% vs. 38.0% in patients receiving other therapies.

Conclusions
The results suggest that neoadjuvant RCT might improve LC and FFDM in patients with localized G3 STS while also being associated with increased acute complication rates. Further prospective research is warranted to confirm these findings.
Uptake of cervical cancer screening and its predictors among women of reproductive age in Gomma district, South West Ethiopia: a community-based cross-sectional study
Authors: Gizaw Abraham Tamirat , El-Khatib Ziad , Wolancho Wadu , Amdissa Demuma , Bamboro Shemsedin , Boltena Minyahil Tadesse , Appiah Seth Christopher Yaw , Asamoah Benedict Oppong , Wasihun Yitbarek , Tareke Kasahun Girma 
Published: August 2022

Abstract
Background
Cervical cancer is a public health challenge despite the available free screening service in Ethiopia. Early screening for cervical cancer significantly improves the chances of successful treatment of pre-cancers and cancers among women of reproductive age. Therefore, this study aimed to assess the uptake of screening and identify the factors among women of reproductive age.

Methods
A community-based cross-sectional study was conducted in Gomma Woreda, Jimma Zone, Ethiopia, from 1st to the 30th of August, 2019. The total sample size was 422. A systematic random sampling technique was employed. Data were collected using a structured questionnaire, entered in epidata, and exported and analyzed using SPSS version 20.0 software packages. Descriptive, bivariate and multivariable logistic regression analyses with 95% CI for odds ratio (OR) were performed to declare a significant predictors.

Result
A total of 382 study participants were involved with a response rate of 90.5%. The mean age of the study participants was 26.45 ± 4.76 SD. One hundred forty-eight (38.7%) of participants had been screened for CC. Marital status (AOR = 10.74, 95%, CI = 5.02–22.96), residence (AOR = 4.45, 95%, CI = 2.85–6.96), educational status (AOR = 1.95, 95% CI = 1.12–3.49), government employee (AOR = 2.61, 95%, CI = 1.33–5.15), birth experience (AOR = 8.92, 95% CI = 4.28–19.19), giving birth at health center and government hospitals (AOR = 10.31, 95% CI = 4.99–21.62; AOR = 5.54, 95% CI = 2.25–13.61); distance from health facility (AOR = 4.41, 95% CI = 2.53–9.41), health workers encouragement (AOR = 3.23, 95% CI = 1.57–6.63), awareness on cervical cancer (AOR = 0.37, 95% CI = 0.19–0.72), awareness about CC screening (AOR = 4.52, 95%, CI = 2.71–7.55) and number of health facility visit per year (AOR = 3.63, 95%, CI = 1.86–6.93) were the predictors for the uptake of cervical cancer screening.

Conclusion
The uptake of cervical cancer screening was low. Marital status, residence, occupation, perceived distance from screening health facility, health workers encouragement, number of health facility visits, birth experience, place of birth, and knowledge about cervical cancer screening were the predictors. There is a need to conduct further studies on continuous social and behavioral change communication.
Foot pain and inflammatory markers: a cross sectional study in older adults
Authors: Siefkas Anna C. , Dufour Alyssa B. , Golightly Yvonne M. , Menz Hylton B. , Hillstrom Howard J. , Hannan Marian T. 
Published: August 2022

AbstractBackgroundFoot disorders may limit independence and reduce quality of life for older adults. Obesity is a risk factor for foot conditions; both mechanical load and metabolic effects may contribute to these conditions. This study determined cross‐sectional associations between inflammatory markers and foot disorders.MethodsParticipants were drawn from the Framingham Foot Study (2002–2008). C‐reactive protein (CRP), interleukin‐6 (IL‐6), and tumor necrosis factor alpha (TNF‐α) were each examined for associations with foot pain, forefoot pain, hindfoot pain, hallux valgus, hallux rigidus, and toe deformities (claw, hammer, or overlapping toes). Unadjusted and adjusted (age, body mass index, physical activity, smoking status) sex‐specific logistic regression was performed.ResultsOf 909 participants, 54% were women (mean age 65 9 years), 20% had foot pain, 29% had hallux valgus, 3% had hallux rigidus, and 27% had toe deformities. In unadjusted models, higher CRP (OR [95% CI] = 1.5 [1.1, 2.0]) and IL‐6 (OR [95% CI] = 1.8 [1.2, 2.6]) were associated with foot pain among men; higher CRP was associated with foot pain (OR [95% CI] = 1.3 [1.0, 1.5]) among women. Higher CRP (OR [95% CI] = 1.9 [1.1, 3.2]) and IL‐6 (OR [95% CI] = 2.4 [1.2, 4.7]) were associated with forefoot pain in men. Higher CRP was associated with hindfoot pain ([95% CI] = 1.8 [1.2, 2.6]) in women. After adjustment, CRP ([95% CI] = 1.5 [1.1, 2.0]) and IL‐6 ([95% CI] = 1.8 [1.2, 2.6]) remained associated with foot pain in men, and IL‐6 with forefoot pain ([95% CI] = 2.9 [1.4, 6.1]) in men. No associations with structural foot disorders were observed.ConclusionsInflammation may impact foot pain. Future work assessing whether inflammation is part of the mechanism linking obesity to foot pain may identify areas for intervention and prevention.