bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are there sex differences in the effect of type 2 diabetes in the incidence and outcomes of myocardial infarction? A matched-pair analysis using hospital discharge data
Authors: Lopez-de-Andres Ana , Jimenez-Garcia Rodrigo , Hernández-Barrera Valentin , de Miguel-Yanes Jose M. , Albaladejo-Vicente Romana , Villanueva-Orbaiz Rosa , Carabantes-Alarcon David , Zamorano-Leon Jose J. , Lopez-Herranz Marta , de Miguel-Diez Javier 
Published: April 2021

Abstract
Background
To analyze incidence, use of therapeutic procedures, and in-hospital outcomes in patients with ST elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI) according to the presence of type 2 diabetes (T2DM) in Spain (2016–2018) and to investigate sex differences.

Methods
Using the Spanish National Hospital Discharge Database, we estimated the incidence of myocardial infarctions (MI) in men and women with and without T2DM aged ≥ 40 years. We analyzed comorbidity, procedures, and outcomes. We matched each man and woman with T2DM with a non-T2DM man and woman of identical age, MI code, and year of hospitalization. Propensity score matching was used to compare men and women with T2DM.

Results
MI was coded in 109,759 men and 44,589 women (30.47% with T2DM). The adjusted incidence of STEMI (IRR 2.32; 95% CI 2.28–2.36) and NSTEMI (IRR 2.91; 95% CI 2.88–2.94) was higher in T2DM than non-T2DM patients, with higher IRRs for NSTEMI in both sexes. The incidence of STEMI and NSTEMI was higher in men with T2DM than in women with T2DM. After matching, percutaneous coronary intervention (PCI) was less frequent among T2DM men than non-T2DM men who had STEMI and NSTEMI. Women with T2DM and STEMI less frequently had a code for PCI that matched that of non-T2DM women. In-hospital mortality (IHM) was higher among T2DM women with STEMI and NSTEMI than in matched non-T2DM women. In men, IHM was higher only for NSTEMI. Propensity score matching showed higher use of PCI and coronary artery bypass graft and lower IHM among men with T2DM than women with T2DM for both STEMI and NSTEMI.

Conclusions
T2DM is associated with a higher incidence of STEMI and NSTEMI in both sexes. Men with T2DM had higher incidence rates of STEMI and NSTEMI than women with T2DM. Having T2DM increased the risk of IHM after STEMI and NSTEMI among women and among men only for NSTEMI. PCI appears to be less frequently used in T2DM patients After STEMI and NSTEMI, women with T2DM less frequently undergo revascularization procedures and have a higher mortality risk than T2DM men.
Stronger association of triglyceride glucose index than the HOMA-IR with arterial stiffness in patients with type 2 diabetes: a real-world single-centre study
Authors: Wang Shujie , Shi Juan , Peng Ying , Fang Qianhua , Mu Qian , Gu Weiqiong , Hong Jie , Zhang Yifei , Wang Weiqing 
Published: April 2021

Abstract
Background
The triglyceride-glucose index (TyG index) has been proposed as a simple and reliable alternative insulin resistance (IR) marker, while the homeostasis model assessment for IR (HOMA-IR) is the most frequently used index. Few studies have evaluated the role of IR assessed by the TyG index and HOMA-IR on arterial stiffness in a type 2 diabetes (T2D) population with a high risk of increased arterial stiffness. We aimed to investigate the association of the TyG index and HOMA-IR with arterial stiffness in patients with T2D.

Methods
We recruited 3185 patients with T2D, who underwent brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness, but without previous cardiovascular disease. Increased arterial stiffness was defined as a baPWV value greater than the 75th percentile (18.15 m/s) in the present study. The TyG index was determined as ln(fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2), and the HOMA-IR was calculated as (fasting insulin [μIU/mL] × fasting glucose [mmol/L])/22.5.

Results
The mean age of the study participants was 54.6 ± 12.0 years, and 1954 (61.4%) were men. Seemingly unrelated regression estimation analysis demonstrated that the TyG index had stronger associations with baPWV than the HOMA-IR (all P < 0.001). In the multivariable logistic analyses, each one-unit increase in the TyG index was associated with a 1.40-fold (95% CI 1.16–1.70, P < 0.001) higher prevalence of increased arterial stiffness, but the prominent association of the HOMA-IR with the prevalence of increased arterial stiffness was not observed. Subgroup analyses showed that a more significant association between the TyG index and the prevalence of increased arterial stiffness was detected in older patients with a longer duration of diabetes and poor glycaemic control (all P < 0.05).

Conclusions
Compared with the HOMA-IR, the TyG index is independently and more strongly associated with arterial stiffness in patients with T2D.
BRD4 PROTAC degrader ARV-825 inhibits T-cell acute lymphoblastic leukemia by targeting 'Undruggable' Myc-pathway genes
Authors: Wu Shuiyan , Jiang You , Hong Yi , Chu Xinran , Zhang Zimu , Tao Yanfang , Fan Ziwei , Bai Zhenjiang , Li Xiaolu , Chen Yanling , Li Zhiheng , Ding Xin , Lv Haitao , Du Xiaoli , Lim Su Lin , Zhang Yongping , Huang Saihu , Lu Jun , Pan Jian , Hu Shaoyan 
Published: April 2021

Abstract
Background
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a high risk of induction failure and poor outcomes, with relapse due to drug resistance. Recent studies show that bromodomains and extra-terminal (BET) protein inhibitors are promising anti-cancer agents. ARV-825, comprising a BET inhibitor conjugated with cereblon ligand, was recently developed to attenuate the growth of multiple tumors in vitro and in vivo. However, the functional and molecular mechanisms of ARV-825 in T-ALL remain unclear. This study aimed to investigate the therapeutic efficacy and potential mechanism of ARV-825 in T-ALL.

Methods
Expression of the BRD4 were determined in pediatric T-ALL samples and differential gene expression after ARV-825 treatment was explored by RNA-seq and quantitative reverse transcription-polymerase chain reaction. T-ALL cell viability was measured by CCK8 assay after ARV-825 administration. Cell cycle was analyzed by propidium iodide (PI) staining and apoptosis was assessed by Annexin V/PI staining. BRD4, BRD3 and BRD2 proteins were detected by western blot in cells treated with ARV-825. The effect of ARV-825 on T-ALL cells was analyzed in vivo. The functional and molecular pathways involved in ARV-825 treatment of T-ALL were verified by western blot and chromatin immunoprecipitation (ChIP).

Results
BRD4 expression was higher in pediatric T-ALL samples compared with T-cells from healthy donors. High BRD4 expression indicated a poor outcome. ARV-825 suppressed cell proliferation in vitro by arresting the cell cycle and inducing apoptosis, with elevated poly-ADP ribose polymerase and cleaved caspase 3. BRD4, BRD3, and BRD2 were degraded in line with reduced cereblon expression in T-ALL cells. ARV-825 had a lower IC50 in T-ALL cells compared with JQ1, dBET1 and OTX015. ARV-825 perturbed the H3K27Ac-Myc pathway and reduced c-Myc protein levels in T-ALL cells according to RNA-seq and ChIP. In the T-ALL xenograft model, ARV-825 significantly reduced tumor growth and led to the dysregulation of Ki67 and cleaved caspase 3. Moreover, ARV-825 inhibited cell proliferation by depleting BET and c-Myc proteins in vitro and in vivo.

Conclusions
BRD4 indicates a poor prognosis in T-ALL. The BRD4 degrader ARV-825 can effectively suppress the proliferation and promote apoptosis of T-ALL cells via BET protein depletion and c-Myc inhibition, thus providing a new strategy for the treatment of T-ALL.
Day-to-day progression of vital-sign circadian rhythms in the intensive care unit
Authors: Davidson Shaun , Villarroel Mauricio , Harford Mirae , Finnegan Eoin , Jorge João , Young Duncan , Watkinson Peter , Tarassenko Lionel 
Published: April 2021

AbstractBackgroundDisrupted vital-sign circadian rhythms in the intensive care unit (ICU) are associated with complications such as immune system disruption, delirium and increased patient mortality. However, the prevalence and extent of this disruption is not well understood. Tools for its detection are currently limited.MethodsThis paper evaluated and compared vital-sign circadian rhythms in systolic blood pressure, heart rate, respiratory rate and temperature. Comparisons were made between the cohort of patients who recovered from the ICU and those who did not, across three large, publicly available clinical databases. This comparison included a qualitative assessment of rhythm profiles, as well as quantitative metrics such as peak–nadir excursions and correlation to a demographically matched ‘recovered’ profile.ResultsCircadian rhythms were present at the cohort level in all vital signs throughout an ICU stay. Peak–nadir excursions and correlation to a ‘recovered’ profile were typically greater throughout an ICU stay in the cohort of patients who recovered, compared to the cohort of patients who did not.ConclusionsThese results suggest that vital-sign circadian rhythms are typically present at the cohort level throughout an ICU stay and that quantitative assessment of these rhythms may provide information of prognostic use in the ICU.
Tuning a bi-enzymatic cascade reaction in Escherichia coli to facilitate NADPH regeneration for ε-caprolactone production
Authors: Xiong Jinghui , Chen Hefeng , Liu Ran , Yu Hao , Zhuo Min , Zhou Ting , Li Shuang 
Published: April 2021

Abstractε-Caprolactone is a monomer of poly(ε-caprolactone) which has been widely used in tissue engineering due to its biodegradability and biocompatibility. To meet the massive demand for this monomer, an efficient whole-cell biocatalytic approach was constructed to boost the ε-caprolactone production using cyclohexanol as substrate. Combining an alcohol dehydrogenase (ADH) with a cyclohexanone monooxygenase (CHMO) in Escherichia coli, a self-sufficient NADPH-cofactor regeneration system was obtained. Furthermore, some improved variants with the better substrate tolerance and higher catalytic ability to ε-caprolactone production were designed by regulating the ribosome binding sites. The best mutant strain exhibited an ε-caprolactone yield of 0.80 mol/mol using 60 mM cyclohexanol as substrate, while the starting strain only got a conversion of 0.38 mol/mol when 20 mM cyclohexanol was supplemented. The engineered whole-cell biocatalyst was used in four sequential batches to achieve a production of 126 mM ε-caprolactone with a high molar yield of 0.78 mol/mol.
RETRACTED - Excess mortality among patients with severe mental disorders and effects of community-based mental healthcare: a community-based prospective study in Sichuan, China
Authors: Li Yaxi , Yan Lijing L. , Ronsmans Carine , Wen Hong , Xu Jiajun , Wang Dan , Yang Min 
Published: April 2021

Background
High-quality primary care reduces premature mortality in the general population, but evidence for psychiatric patients in China is scarce.

Aims
To confirm excess mortality in patients with severe mental illness (SMI), and to examine the impact of community-based mental healthcare and other risk factors on their mortality.

Method
We included 93 655 patients in 2012 and 100 706 in 2013 from the national mental health surveillance system in Sichuan, China to calculate the standardised mortality ratio (SMR). A total of 112 576 patients were followed up from 2009 to 2014 for model analyses. We used growth models to quantify the patterns of change for community management measures, high-risk behaviour, disease stability and medication adherence of patients over time, and then used multilevel proportional hazard models to examine the association between change patterns of management measures and mortality.

Results
The SMR was 6.44 (95% CI 4.94–8.26) in 2012 and 7.57 (95% CI 5.98–9.44) in 2013 among patients with SMI aged 15–34 years, and diminished with age. Unfavourable baseline socioeconomic status increased the hazard of death by 38–50%. Positive changes in high-risk behaviour, disease stability and medication adherence had a 54% (95% CI 47–60%), 69% (95% CI 63–73%) and 20% (4–33%) reduction in hazard of death, respectively, versus in those where these were unchanged.

Conclusions
High excess mortality was confirmed among younger patients with SMI in Sichuan, China. Our findings on the relationships between community management and socioeconomic factors and mortality can inform community-based mental healthcare policies to reduce excess mortality among patients with SMI.
Oncology Clinical Trials in Africa: Partnering for Quality
Authors: Shamley Delva , Ezeani Adaora , Okoye Ifeoma 
Published: April 2021

Oncology clinical trials are requisite for testing the safety and effectiveness of promising treatments and deciphering new knowledge into concrete benefits for patients. They present opportunities to innovate promising, novel cancer remedies. A dearth of local evidence to guide cancer treatment in Africans is creating an increased interest in oncology clinical trials to improve patient care. This is primarily because of limitations in pathology, surgery, medical oncology, radiation, and palliation that are leading to worse cancer outcomes on the continent. Investment in oversight of Human Research Ethics committees and Medicines Regulatory Authorities in Africa has improved the potential for many countries to host clinical trials. However, the distribution of cancer trials remains poor across the continent, resulting in inadequate treatment options for patients with cancer. There are some initiatives aimed at developing research capacity to host trials in Africa. However, there is now a need to establish strategic partnerships whose aim should be to achieve harmonized, accredited Clinical Trials Units capable of running trials to meet Good Clinical Practice standards. This article discusses what has been achieved and proposes a model for quality oversight of Clinical Trials Units in Africa.
Effects of Behavioral Weight Loss and Metformin on IGFs in Cancer Survivors: A Randomized Trial
Authors: Yeh Hsin-Chieh , Maruthur Nisa M , Wang Nae-Yuh , Jerome Gerald J , Dalcin Arlene T , Tseng Eva , White Karen , Miller Edgar R , Juraschek Stephen P , Mueller Noel T , Charleston Jeanne , Durkin Nowella , Hassoon Ahmed , Lansey Dina G , Kanarek Norma F , Carducci Michael A , Appel Lawrence J 
Published: April 2021

Abstract

Context
Higher levels of insulin-like growth factor-1 (IGF-1) are associated with increased risk of cancers and higher mortality. Therapies that reduce IGF-1 have considerable appeal as means to prevent recurrence.

Design
Randomized, 3-parallel-arm controlled clinical trial.

Interventions and Outcomes
Cancer survivors with overweight or obesity were randomized to (1) self-directed weight loss (comparison), (2) coach-directed weight loss, or (3) metformin treatment. Main outcomes were changes in IGF-1 and IGF-1:IGFBP3 molar ratio at 6 months. The trial duration was 12 months.

Results
Of the 121 randomized participants, 79% were women, 46% were African Americans, and the mean age was 60 years. At baseline, the average body mass index was 35 kg/m2; mean IGF-1 was 72.9 (SD, 21.7) ng/mL; and mean IGF1:IGFBP3 molar ratio was 0.17 (SD, 0.05). At 6 months, weight changes were -1.0% (P = 0.07), -4.2% (P &lt; 0.0001), and -2.8% (P &lt; 0.0001) in self-directed, coach-directed, and metformin groups, respectively. Compared with the self-directed group, participants in metformin had significant decreases on IGF-1 (mean difference in change: -5.50 ng/mL, P = 0.02) and IGF1:IGFBP3 molar ratio (mean difference in change: -0.0119, P = 0.011) at 3 months. The significant decrease of IGF-1 remained in participants with obesity at 6 months (mean difference in change: -7.2 ng/mL; 95% CI: -13.3 to -1.1), but not in participants with overweight (P for interaction = 0.045). There were no significant differences in changes between the coach-directed and self-directed groups. There were no differences in outcomes at 12 months.

Conclusions
In cancer survivors with obesity, metformin may have a short-term effect on IGF-1 reduction that wanes over time.
Clinical Presentation and Perioperative Management of Pheochromocytomas and Paragangliomas: A 4-Decade Experience
Authors: Uslar Thomas , San Francisco Ignacio F , Olmos Roberto , Macchiavelo Stefano , Zuñiga Alvaro , Rojas Pablo , Garrido Marcelo , Huete Alvaro , Mendez Gonzalo P , Cortinez Ignacio , Zemelman José Tomás , Cifuentes Joaquín , Castro Fernando , Olivari Daniela , Domínguez José Miguel , Arteaga Eugenio , Fardella Carlos E , Valdés Gloria , Tagle Rodrigo , Baudrand Rene 
Published: April 2021

Abstract

Purpose
Latin American reports on pheochromocytomas and paragangliomas (PPGLs) are scarce. Recent studies demonstrate changes in clinical presentation and management of these patients. Herein, we assessed the main characteristics of PPGL patients in our academic center over the past 4 decades.

Methods
Demographic, clinical, biochemical, and perioperative data from 105 PPGL patients were retrospectively and prospectively collected over the 1980–2019 period. Data were organized into 4 periods by decade.

Results
Age at diagnosis, gender, tumor size and percentage of bilaterality, percentage of paragangliomas, and metastases remained stable across the 4 decades. The proportion of genetic testing and incidentalomas increased in recent decades (all P &lt; 0.001). Therefore, we compared PPGLs diagnosed as incidentalomas (36%) with those clinically suspected (64%). Incidentalomas had fewer adrenergic symptoms (38 vs. 62%; P &lt; 0.001) and lower rates of hypertension (64% vs. 80%; P = 0.01) and hypertensive crisis (28% vs. 44%; P = 0.02); also, they had lower functionality (79% vs. 100%; P = 0.01) and lower catecholamines levels (8.4-fold vs. 12.5-fold above upper cutoffs; P = 0.04). Regarding management of all PPGLs over the decades, we observed significant increases in both perioperative doxazosin dose (P = 0.003) and laparoscopic approach rates (P &lt; 0.001), along with a decrease in the length of hospital stays (P = 0.007).

Conclusions
We observed a change in the clinical presentation of PPGL in recent decades, with a marked increase in incidental cases and milder symptoms. The implementation of a multidisciplinary program for adrenal disorders in our institution has translated into more timely diagnoses, more genetic testing, and improvements in perioperative management.
The control of root, vegetative shoot and flower morphogenesis in tobacco thin cell-layer expiants (TCLs)
Authors: Mohnen Debra , Eberhard Stefan , Marfà Victôria , Doubrava Nancy , Toubart Patrick , Gollin David J. , Gruber Teresa A. , Nuri Walid , Albersheim Peter , Darvill Alan 
Published: April 2021

ABSTRACT
Thin cell-layer explants (TCLs) have been proposed as favorable tissues for the study of root, vegetative shoot and flower formation. We tested the effects of pH, light quality, light quantity, and IBA and kinetin concentrations on the morphogenesis of TCLs cultured individually on a liquid medium. Alterations of the amounts of exogenously supplied IBA and kinetin were sufficient to induce the formation of roots, vegetative shoots and flowers on TCLs cultured on otherwise identical media. The type and number of organs formed were sensitive to the intensity of light (55, 75, 100 and 120μEinsteins m-2sec-1) under which TCLs were grown. Evidence was obtained that the effects of light on TCL morphogenesis were associated with photochemical degradation of IBA in the medium. Evaluation of the organogenesis that occurred in TCLs cultured on a medium containing a range of IBA and kinetin concentrations showed that the number and type of organs formed, and overall growth, were dependent upon the initial concentrations of auxin and cytokinin. We have developed the TCL culture system into a sensitive and reproducible bioassay for the study of morphogenesis. The advantages of using the TCL morphogenesis bioassay for the identification and study of molecules (e.g. cell wall oligosaccharides) that may regulate morphogenesis are discussed.
Naturally O-N-S Co-Doped Carbon with Multiscale Pore Architecture Derived from Lotus Leaf Stem for High-Performance Supercapacitors
Authors: Liu Huan , Chen Wei , Zhang Rongli , Ren Yiming 
Published: April 2021

Abstract
Lotus leaf stem is successfully exploited as a sustainable biomass to fabricate multi-heteroatom co-doped carbon with multiscale pore architecture by a readily scalable and effective strategy of pre-carbonization and KOH activation. By taking advantage of 3D hierarchical structure with high surface area and optimized pore size distribution, naturally O-N-S co-doping and nanosized graphitic structure (contributing to large accessible surface for charge storage, short ion diffusion distance, rapid charge transfer and low internal resistance), as-produced carbon is demonstrated as a promising electrode for supercapacitors with a high capacitance of 425 F/g at 0.5 A/g in a three-electrode system and 295 F/g at 0.1 A/g with superb rate capability (84% retention from 0.2 to 20 A/g) and outstanding recyclability (97.8% retention after 10000 charge-discharge cycles at 10 A/g) in a two-electrode system with KOH solution. The excellent recyclability of 93.3% is also achieved after 10000 cycles at 10 A/g for the symmetric supercapacitor using Na2SO4 electrolyte. These values may boost the commercial application of biomass-derived carbon for energy storage.
Preparation and Catalytic Performance of Highly Stable Silica-Coated Gold Nanorods Supported on Alumina
Authors: Imura Yoshiro , Fukuda Kunihiro , Saito Haruna , Maniwa Motoki , Kurihara Yusuke , Morita-Imura Clara , Kawai Takeshi 
Published: April 2021

Abstract
Shape-controlled metal nanocrystals such as nanorods are attractive because of their potential novel catalytic properties. It is important to improve the stability of the shape-controlled nanocrystals to be applied as nanocatalysts. In this study, α-Al2O3-supported Au nanorods (AuNR/α-Al2O3) and silica-coated α-Al2O3-supported Au nanorods (SiO2/AuNR/α-Al2O3) were prepared as alcohol oxidation catalysts for the transformation of 1-phenylethyl alcohol to acetophenone. The formation rate of acetophenone over AuNR/α-Al2O3 is higher than that over α-Al2O3-supported spherical Au nanoparticles obtained by calcining AuNR/α-Al2O3. In addition, SiO2/AuNR/α-Al2O3 exhibits higher catalytic performance and thermal stability than those of AuNR/α-Al2O3 in alcohol oxidation.