bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of the COVID-19 Pandemic on Treatment Times for Acute Ischemic Stroke
Authors: Siegler James E. , Zha Alicia M. , Czap Alexandra L. , Ortega-Gutierrez Santiago , Farooqui Mudassir , Liebeskind David S. , Desai Shashvat M. , Hassan Ameer E. , Starosciak Amy K. , Linfante Italo , Rai Vivek , Thon Jesse M. , Then Ryna , Heslin Mark E. , Thau Lauren , Khandelwal Priyank , Mohammaden Mahmoud H. , Haussen Diogo C. , Nogueira Raul G. , Jillella Dinesh V. , Nahab Fadi , Kaliaev Artem , Nguyen Thanh N. , Zaidat Osama , Jovin Tudor G. , Jadhav Ashutosh P. 
Published: November 2020

Background and Purpose:
The pandemic caused by the novel coronavirus disease 2019 (COVID-19) has led to an unprecedented paradigm shift in medical care. We sought to evaluate whether the COVID-19 pandemic may have contributed to delays in acute stroke management at comprehensive stroke centers.

Methods:
Pooled clinical data of consecutive adult stroke patients from 14 US comprehensive stroke centers (January 1, 2019, to July 31, 2020) were queried. The rate of thrombolysis for nontransferred patients within the Target: Stroke goal of 60 minutes was compared between patients admitted from March 1, 2019, and July 31, 2019 (pre–COVID-19), and March 1, 2020, to July 31, 2020 (COVID-19). The time from arrival to imaging and treatment with thrombolysis or thrombectomy, as continuous variables, were also assessed.

Results:

Of the 2955 patients who met inclusion criteria, 1491 were admitted during the pre–COVID-19 period and 1464 were admitted during COVID-19, 15% of whom underwent intravenous thrombolysis. Patients treated during COVID-19 were at lower odds of receiving thrombolysis within 60 minutes of arrival (odds ratio, 0.61 [95% CI, 0.38–0.98];
P
=0.04), with a median delay in door-to-needle time of 4 minutes (
P
=0.03). The lower odds of achieving treatment in the Target: Stroke goal persisted after adjustment for all variables associated with earlier treatment (adjusted odds ratio, 0.55 [95% CI, 0.35–0.85];
P
<0.01). The delay in thrombolysis appeared driven by the longer delay from imaging to bolus (median, 29 [interquartile range, 18–41] versus 22 [interquartile range, 13–37] minutes;
P
=0.02). There was no significant delay in door-to-groin puncture for patients who underwent thrombectomy (median, 83 [interquartile range, 63–133] versus 90 [interquartile range, 73–129] minutes;
P
=0.30). Delays in thrombolysis were observed in the months of June and July.

Conclusions:
Evaluation for acute ischemic stroke during the COVID-19 period was associated with a small but significant delay in intravenous thrombolysis but no significant delay in thrombectomy time metrics. Taking steps to reduce delays from imaging to bolus time has the potential to attenuate this collateral effect of the pandemic.
Enhanced Equivalence Projective Simulation: A Framework for Modeling Formation of Stimulus Equivalence Classes
Authors: Mofrad Asieh Abolpou , Yazidi Anis , Mofrad Samaneh Abolpour , Hammer Hugo L. , Arntzen Erik 
Published: November 2020

Abstract
Formation of stimulus equivalence classes has been recently modeled through equivalence projective simulation (EPS), a modified version of a projective simulation (PS) learning agent. PS is endowed with an episodic memory that resembles the internal representation in the brain and the concept of cognitive maps. PS flexibility and interpretability enable the EPS model and, consequently the model we explore in this letter, to simulate a broad range of behaviors in matching-to-sample experiments. The episodic memory, the basis for agent decision making, is formed during the training phase. Derived relations in the EPS model that are not trained directly but can be established via the network's connections are computed on demand during the test phase trials by likelihood reasoning. In this letter, we investigate the formation of derived relations in the EPS model using network enhancement (NE), an iterative diffusion process, that yields an offline approach to the agent decision making at the testing phase. The NE process is applied after the training phase to denoise the memory network so that derived relations are formed in the memory network and retrieved during the testing phase. During the NE phase, indirect relations are enhanced, and the structure of episodic memory changes. This approach can also be interpreted as the agent's replay after the training phase, which is in line with recent findings in behavioral and neuroscience studies. In comparison with EPS, our model is able to model the formation of derived relations and other features such as the nodal effect in a more intrinsic manner. Decision making in the test phase is not an ad hoc computational method, but rather a retrieval and update process of the cached relations from the memory network based on the test trial. In order to study the role of parameters on agent performance, the proposed model is simulated and the results discussed through various experimental settings.
Advancing health-enhancing physical activity at workplace: Sport4Heath 2020 scientific forum
Authors: Todorovic Nikola , Stajer Valdemar , Harrison Bojana , Korovljev Darinka , Maksimovic Neboja , Ostojic Sergej M. 
Published: November 2020

AbstractPhysical activity at workplace can positively impact various wellbeing outcomes yet developing and implementing exercise programs that are straightforward, time-efficient and widely applicable remains a notable public health challenge. Sport4Health Network (SPORT4H) project co-funded by the European Union Erasmus+ programme unites health and sport professionals in an effort to encourage participation in physical activity among working population and reduce health risk factors for lifestyle diseases. A two-day SPORT4H scientific forum on non-traditional types of work-place exercise interventions was organized from 14th to 15th September 2020, to critically evaluate evidence on stretching and resistance exercise programs targeted to working population in aim to identify knowledge gaps and future areas of research and application. Evidence on traditional interventions (e.g., walking initiatives, active travel) appears more robust while only few studies evaluated the applicability of non-traditional PA programs in working population. However, we identified a moderate-to-strong link between non-traditional PA programs at the workplace and several health-related physical fitness indices, with resistance exercise turned out to be superior to other exercise interventions analyzed. It appears that low-volume high-repetition resistance exercise favorably affects musculoskeletal disorders, work performance and health-related quality of life in employees who exercised at least 3 times per week for over 8 weeks. In terms of safety, screening protocols should employ health-related questionnaires, adopting a progressive training load, and prescribing training programs to individual participants’ needs. Implementing non-traditional PA programs aimed to improve health-related physical fitness and counteract sedentary behavior at workplace might be therefore of utmost importance to contribute to health promotion in this sensible population.
Serum surfactant protein D as a predictive biomarker for the efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis: a post-hoc analysis of the phase 3 trial in Japan
Authors:   Pirfenidone Clinical Study Group in Japan, Ikeda Kimiyuki , Chiba Hirofumi , Nishikiori Hirotaka , Azuma Arata , Kondoh Yasuhiro , Ogura Takashi , Taguchi Yoshio , Ebina Masahito , Sakaguchi Hiroki , Miyazawa Shogo , Suga Moritaka , Sugiyama Yukihiko , Nukiwa Toshihiro , Kudoh Shoji , Takahashi Hiroki 
Published: November 2020

Abstract
Background
Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease course. The recent advancement of antifibrotic therapy has increased the need for reliable and specific biomarkers. This study aimed to assess alveolar epithelial biomarkers as predictors for the efficacy of the antifibrotic drug pirfenidone.

Methods
We conducted a post-hoc analysis of the prospective, multicenter, randomized, placebo-controlled, phase 3 trial of pirfenidone in Japan (total, n = 267; pirfenidone, n = 163; placebo, n = 104). Logistic regression analysis was performed to extract parameters that predicted disease progression, defined by a ≥ 10% relative decline in vital capacity (VC) from baseline and/or death, at week 52. For assessment of serum surfactant protein (SP)-D, SP-A and Krebs von den Lungen (KL)-6, all patients were dichotomized by the median concentration of each biomarker at baseline to the high and low biomarker subgroups. Associations of these concentrations were examined with changes in VC at each time point from baseline up to week 52, along with progression-free survival (PFS). Additionally, the effect of pirfenidone treatment on serial longitudinal concentrations of these biomarkers were evaluated.

Results
In the multivariate logistic regression analysis, body mass index (BMI), %VC and SP-D in the pirfenidone group, and BMI and %VC in the placebo group were indicated as predictors of disease progression. Pirfenidone treatment reduced the decline in VC with statistical significance in the low SP-D and low SP-A subgroups over most of the treatment period, and also prolonged PFS in the low SP-D and low KL-6 subgroups. Furthermore, SP-D levels over time course were reduced in the pirfenidone group from as early as week 8 until the 52-week treatment period compared with the placebo group.

Conclusions
Serum SP-D was the most consistent biomarker for the efficacy of pirfenidone in the cohort trial of IPF. Serial measurements of SP-D might have a potential for application as a pharmacodynamic biomarker.
Trial registration The clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13, 2005 (registration No. JapicCTI-050121; http://Clinicaltrials.jp)
Prognostic factors in pulmonary metastasectomy and efficacy of repeat pulmonary metastasectomy from colorectal cancer
Authors: Fukada Masahiro , Matsuhashi Nobuhisa , Takahashi Takao , Tanaka Yoshihiro , Okumura Naoki , Yamamoto Hirotaka , Shirahashi Koyo , Iwata Hisashi , Doi Kiyoshi , Yoshida Kazuhiro 
Published: November 2020

Abstract
Background
The rate of pulmonary metastasectomy from colorectal cancer (CRC) has increased with recent advances in chemotherapy, diagnostic techniques, and surgical procedures. The purpose of this study was to investigate the prognostic factors for response to pulmonary metastasectomy and the efficacy of repeat pulmonary metastasectomy.

Methods
This study was a retrospective, single-institution study of 126 CRC patients who underwent pulmonary metastasectomy between 2000 and 2019 at the Gifu University Hospital.

Results
The 3- and 5-year survival rates were 84.9% and 60.8%, respectively. Among the 126 patients, 26 (20.6%) underwent a second pulmonary metastasectomy for pulmonary recurrence after initial pulmonary metastasectomy. Univariate analysis of survival identified seven significant factors: (1) gender (p = 0.04), (2) past history of extra-thoracic metastasis (p = 0.04), (3) maximum tumor size (p = 0.002), (4) mediastinal lymph node metastasis (p = 0.02), (5) preoperative carcinoembryonic antigen (CEA) level (p = 0.01), (6) preoperative carbohydrate antigen 19-9 (CA19-9) level (p = 0.03), and (7) repeat pulmonary metastasectomy for pulmonary recurrence (p < 0.001). On multivariate analysis, only mediastinal lymph node metastasis (p = 0.02, risk ratio 8.206, 95% confidence interval (CI) 1.566–34.962) and repeat pulmonary metastasectomy for pulmonary recurrence (p < 0.001, risk ratio 0.054, 95% CI 0.010–0.202) were significant. Furthermore, in the evaluation of surgical outcomes, the safety of second pulmonary metastasectomy was almost the same as that of initial pulmonary metastasectomy.

Conclusions
Repeat pulmonary metastasectomy is likely to be safe and effective for recurrent cases that meet the surgical criteria. However, mediastinal lymph node metastasis was a significant independent prognostic factor for worse overall survival.
Catechins from oolong tea improve uterine defects by inhibiting STAT3 signaling in polycystic ovary syndrome mice
Authors: Hong Ge , Wu Hao , Ma Shi-Tang , Su Zhe 
Published: November 2020

AbstractBackgroundIt is showed that inflammation is causative factor for PCOS, leading to a decline in ovarian fertility. Previous studies have reported that tea consumption can reduce the incidence of ovarian cancer. We speculate that catechins from oolong tea (Camellia sinensis (L.) O.Kuntze) may have a potential therapeutic effect on PCOS. This study aims to investigate the effects of oolong tea catechins on the uterus of polycystic ovary syndrome (PCOS) mice induced by insulin combined with human chorionic gonadotropin (hCG).MethodsSixty female mice were divided into 6 groups (n = 10): model, model + Metformin 200 mg/kg, model + catechins 25 mg/kg, model + catechins 50 mg/kg, and model + catechins 100 mg/kg. Another forty female mice were divided into 4 groups (n = 10): control, control + catechins 100 mg/kg, model, and model + catechins 100 mg/kg. Ovarian and uterine weight coefficients, sex hormone levels, glucose metabolism and insulin resistance, and ovarian and uterine pathology were examined. Changes in NF-κB-mediated inflammation, MMP2 and MMP9 expressions, and STAT3 signaling were evaluated in the uterus of mice.ResultsCatechins could effectively reduce the ovarian and uterine organ coefficients, reduce the levels of E2, FSH and LH in the blood and the ratio of LH/FSH, and improve glucose metabolism and insulin resistance in PCOS mice induced by insulin combined with hCG. In addition, catechins could significantly down-regulated the expression of p-NF-κB p65 in the uterus and the protein expressions of the pro-inflammatory factors (IL-1β, IL-6, and TNF-α). The expressions of mmp2 and mmp9 associated with matrix degradation in uterine tissue were also significantly down-regulated by catechins. Further, catechins significantly reduced the expression of p-STAT3 and increased the expression of p-IRS1 and p-PI3K in the uterus of PCOS mice.ConclusionCatechins from oolong tea can alleviate ovarian dysfunction and insulin resistance in PCOS mice by inhibiting uterine inflammation and matrix degradation via inhibiting p-STAT3 signaling.
KLF7: a new candidate biomarker and therapeutic target for high-grade serous ovarian cancer
Authors: De Donato Marta , Babini Gabriele , Mozzetti Simona , Buttarelli Marianna , Ciucci Alessandra , Arduini Gloria , De Rosa Maria Cristina , Scambia Giovanni , Gallo Daniela 
Published: November 2020

Abstract
Background
In spite of great progress in the surgical and clinical management, until now no significant improvement in overall survival of High-Grade Serous Ovarian Cancer (HGSOC) patients has been achieved. Important aspects for disease control remain unresolved, including unclear pathogenesis, high heterogeneity and relapse resistance after chemotherapy. Therefore, further research on molecular mechanisms involved in cancer progression are needed to find new targets for disease management. The Krüppel-like factors (KLFs) are a family of transcriptional regulators controlling several basic cellular processes, including proliferation, differentiation and migration. They have been shown to play a role in various cancer-relevant processes, in a context-dependent way.

Methods
To investigate a possible role of KLF family members as prognostic biomarkers, we carried out a bioinformatic meta-analysis of ovarian transcriptome datasets in different cohorts of late-stage HGSOC patients. In vitro cellular models of HGSOC were used for functional studies exploring the role of KLF7 in disease development and progression. Finally, molecular modelling and virtual screening were performed to identify putative KLF7 inhibitors.

Results
Bioinformatic analysis highlighted KLF7 as the most significant prognostic gene, among the 17 family members. Univariate and multivariate analyses identified KLF7 as an unfavourable prognostic marker for overall survival in late-stage TCGA-OV and GSE26712 HGSOC cohorts.
Functional in vitro studies demonstrated that KLF7 can play a role as oncogene, driving tumour growth and dissemination. Mechanistic targets of KLF7 included genes involved in epithelial to mesenchymal transition, and in maintaining pluripotency and self-renewal characteristics of cancer stem cells. Finally, in silico analysis provided reliable information for drug-target interaction prediction.

Conclusions
Results from the present study provide the first evidence for an oncogenic role of KLF7 in HGSOC, suggesting it as a promising prognostic marker and therapeutic target.
Psychometric evaluation of the Farsi version of the diabetes foot self‐care bahavior scale
Authors: Hasanpour Dehkordi Ali , Chin Yen‐Fan , Huang Tzu‐Ting , Ebadi Abbas , Ghanei Gheshlagh Reza 
Published: November 2020

AbstractBackgroundDiabetes foot self‐care is one of the self‐management behaviors of diabetic patients leading to a reduction in the incidence of pressure ulcers and amputation. Having a valid, reliable, simple and comprehensive tool is essential in measuring the self‐care behavior of diabetic patients. The aim of this study was to evaluate the psychometric properties of the Farsi version of the diabetes foot self‐care bahavior scale (DFSBS) in Iran.MethodsIn this cross‐sectional and methodological study, 500 patients with type 2 diabetes were recruited by convenience sampling. Construct validity was assessed by exploratory factor analysis (over 300 patients) and confirmatory factor analysis (over 200 patients). Internal consistency was calculated by Cronbach's alpha coefficient and its stability was calculated by intraclass correlation coefficient (ICC).ResultsIn the exploratory factor analysis, two self‐care factors related to feet and shoes were extracted which had specific values of 38.49 and 1.24, respectively, and were able to account for 56.22% of the total self‐care variance of diabetes foot. Confirmatory factor analysis had excellent fit model. The internal consistency and ICC of the whole instrument were 0.83 and 0.791 (95% CI: 0.575–0.925; P < 0.001), respectively.ConclusionsThe Farsi version of DFSBS (F‐DFSBS) has good validity and reliability, and due to its appropriate psychometric properties, this tool can be used in future studies.
Comparison of reversal of rat pulmonary fibrosis of nintedanib, pirfenidone, and human umbilical mesenchymal stem cells from Wharton’s jelly
Authors: Chu Kuo-An , Yeh Chang-Ching , Kuo Fu-Hsien , Lin Wen-Ren , Hsu Chien-Wei , Chen Tien-Hua , Fu Yu-Show 
Published: November 2020

Abstract
Background
The present study compared the effects of antifibrotic medications, pirfenidone, and nintedanib, with transplantation of human umbilical mesenchymal stem cells (HUMSCs) in restoring rat pulmonary fibrosis (PF).

Methods
A stable animal model was established via an intratracheal injection of 5 mg bleomycin (BLM). One single transplantation of 2.5× 107 HUMSCs or initiation of daily oral nintedanib/pirfenidone administration was performed on day 21 following BLM damage.

Results
Pulmonary function examination revealed that BLM rats exhibited a significant decrease in blood oxygen saturation and an increase in respiratory rates. While no significant improvements were found in BLM rats receiving nintedanib or pirfenidone, those who transplanted with HUMSCs showed a statistical amelioration in blood oxygen saturation and significant alleviation in respiratory rates. Quantification results revealed that a significant reduction in alveolar space and marked increases in substantial cell infiltration and collagen deposition in the left lungs of BLM rats. No significant alteration was observed in BLM rats administered nintedanib or pirfenidone. However, BLM rats transplanted with HUMSCs had a significant recovery in alveolar space and noticeable decreases in cell infiltration and collagen deposition. The inflammatory cell numbers in the bronchoalveolar lavage was increased in the BLM group. While the rats treated with nintedanib or pirfenidone had a lower cell number than the BLM group, a higher cell number was found as compared with the Normal group. In rats transplanted with HUMSCs, the cell number did not differ from the Normal group.

Conclusions
Transplantation of HUMSCs could effectively treat PF as opposed to the administration of anti-fibrotic drugs with nintedanib or pirfenidone with a significant better result in lung volume, pathological changes, lung function, and blood oxygen saturation.
Unexpected increase of myocardial extracellular volume fraction in low cardiovascular risk HIV patients
Authors: Borrazzo Cristian , d’Ettorre Gabriella , Ceccarelli Giancarlo , Pacilio Massimiliano , Santinelli Letizia , Cavallari Eugenio Nelson , Spagnolello Ornella , Silvestri Valeria , Vassalini Paolo , Scagnolari Carolina , Francone Marco , Mastroianni Claudio Maria , Carbone Iacopo 
Published: November 2020

Abstract
Background
People living with HIV (PLWH) are prone to develop sub-clinical Cardiovascular (CV) disease, despite the effectiveness of combined Antiretroviral Therapy (cART). Algorithms developed to predict CV risk in the general population could be inaccurate when applied to PLWH. Myocardial Extra-Cellular Matrix (ECM) expansion, measured by computed tomography, has been associated with an increased CV vulnerability in HIV-negative population. Measurement of Myocardial Extra-Cellular Volume (ECV) by computed tomography or magnetic resonance, is considered a useful surrogate for clinical evaluation of ECM expansion. In the present study, we aimed to determine the extent of cardiovascular involvement in asymptomatic HIV-infected patients with the use of a comprehensive cardiac computed tomography (CCT) approach.

Materials and methods
In the present study, ECV in low atherosclerotic CV risk PLWH was compared with ECV of age and gender matched HIV- individuals. 53 asymptomatic HIV + individuals (45 males, age 48 (42.5–48) years) on effective cART (CD4 + cell count: 450 cells/µL (IQR: 328–750); plasma HIV RNA: <37 copies/ml in all subjects) and 18 age and gender matched controls (14 males, age 55 (44.5–56) years) were retrospectively enrolled. All participants underwent CCT protocol to obtain native and postcontrast Hounsfield unit values of blood and myocardium, ECM was calculated accordingly.

Results
The ECV was significantly higher in HIV + patients than in the control group (ECV: 31% (IQR: 28%-31%) vs. 27.4% (IQR: 25%-28%), p < 0.001). The duration of cART (standardized β = 0.56 (0.33–0.95), p = 0.014) and the years of exposure to HIV infection (standardized β = 0.53 (0.4–0.92), p < 0.001), were positively and strongly associated with ECV values. Differences in ECV (p < 0.001) were also observed regarding the duration of cART exposure (< 5 years, 5–10 years and > 10 years). Moreover, ECV was independently associated with age of participants (standardized β = 0.42 (0.33–0.89), p = 0.084).

Conclusions
HIV infection and exposure to antiretrovirals play a detrimental role on ECV expansion. An increase in ECV indicates ECM expansion, which has been associated to a higher CV risk in the general population. The non-invasive evaluation of ECM trough ECV could represent an important tool to further understand the relationship between HIV infection, cardiac pathophysiology and the increased CV risk observed in PLWH.