bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antizyme Inhibitor 1 Regulates Matrikine Expression and Enhances the Metastatic Potential of Aggressive Primary Prostate Cancer
Authors: Van den Broeck Thomas , Moris Lisa , Gevaert Thomas , Davicioni Elai , Boeckx Bram , Lambrechts Diether , Helsen Christine , Handle Florian , Ghesquière Bart , Soenen Stefaan , Smeets Elien , Eerlings Roy , El Kharraz Sarah , Devlies Wout , Karnes R. Jeffrey , Lotan Tamara , Van Poppel Hendrik , Joniau Steven , Claessens Frank 
Published: January 2022

Abstract

Molecular drivers of metastasis in patients with high-risk localized prostate cancer are poorly understood. Therefore, we aim to study molecular drivers of metastatic progression in patients with high-risk prostate cancer. A retrospective matched case-control study of two clinico-pathologically identical groups of patients with high-risk prostate cancer was undertaken. One group developed metastatic recurrence (n = 19) while the other did not (n = 25). The primary index tumor was identified by a uro-pathologist, followed by DNA and RNA extraction for somatic copy-number aberration (SCNA) analysis and whole-transcriptome gene expression analysis. In vitro and in vivo studies included cell line manipulation and xenograft models.

The integrative CNA and gene expression analyses identified an increase in Antizyme Inhibitor 1 (AZIN1) gene expression within a focal amplification of 8q22.3, which was associated with metastatic recurrence of patients with high-risk prostate cancer in four independent cohorts. The effects of AZIN1 knockdown were evaluated, due to its therapeutic potential. AZIN1 knockdown effected proliferation and metastatic potential of prostate cancer cells and xenograft models. RNA sequencing after AZIN1 knockdown in prostate cancer cells revealed upregulation of genes coding for collagen subunits. The observed effect on cell migration after AZIN1 knockdown was mimicked when exposing prostate cancer cells to bio-active molecules deriving from COL4A1 and COL4A2. Our integrated CNA and gene expression analysis of primary high-risk prostate cancer identified the AZIN1 gene as a novel driver of metastatic progression, by altering collagen subunit expression. Future research should further investigate its therapeutic potential in preventing metastatic recurrence.

Implications:
AZIN1 was identified as driver of metastatic progression in high-risk prostate cancer through matrikine regulation.
HIPK2 Cooperates with KRAS Signaling and Associates with Colorectal Cancer Progression
Authors: Di Segni Micol , Virdia Ilaria , Verdina Alessandra , Amoreo Carla Azzurra , Baldari Silvia , Toietta Gabriele , Diodoro Maria Grazia , Mottolese Marcella , Sperduti Isabella , Moretti Fabiola , Buglioni Simonetta , Soddu Silvia , Di Rocco Giuliana 
Published: January 2022

Abstract

Homeodomain-interacting protein kinase 2 (HIPK2) is an evolutionary conserved kinase that has gained attention as a fine tuner of multiple signaling pathways, among which those commonly altered in colorectal cancer. The aim of this study was to evaluate the relationship of HIPK2 expression with progression markers and mutational pattern and gain insights into the contribution of HIPK2 activity in colorectal cancer. We evaluated a retrospective cohort of colorectal cancer samples by IHC for HIPK2 expression and by next-generation sequencing (NGS) for the detection of mutations of cancer associated genes. We show that the percentage of HIPK2-positive cells increases with tumor progression, significantly correlates with tumor–node–metastasis (TNM) staging and associates with a worse outcome. In addition, we observed that high HIPK2 expression significantly associates with KRAS mutations but not with other cancer-related genes. Functional characterization of the link between HIPK2 and KRAS show that activation of the RAS pathway either due to KRAS mutation or via upstream receptor stimulation, increases HIPK2 expression at the protein level. Of note, HIPK2 physically participates in the active RAS complex while HIPK2 depletion impairs ERK phosphorylation and the growth of tumors derived from KRAS mutated colorectal cancer cells. Overall, this study identifies HIPK2 as a prognostic biomarker candidate in patients with colorectal cancer and underscores a previously unknown functional link between HIPK2 and the KRAS signaling pathway.

Implications:
Our data indicate HIPK2 as a new player in the complex picture of the KRAS signaling network, providing rationales for future clinical studies and new treatment strategies for KRAS mutated colorectal cancer.
Inactivation of p21-Activated Kinase 2 (Pak2) Inhibits the Development of Nf2-Deficient Tumors by Restricting Downstream Hedgehog and Wnt Signaling
Authors: Sementino Eleonora , Kadariya Yuwaraj , Cheung Mitchell , Menges Craig W. , Tan Yinfei , Kukuyan Anna-Mariya , Shrestha Ujjawal , Karchugina Sofiia , Cai Kathy Q. , Peri Suraj , Duncan James S. , Chernoff Jonathan , Testa Joseph R. 
Published: January 2022

Abstract

Because loss of the NF2 tumor suppressor gene results in p21-activated kinase (Pak) activation, PAK inhibitors hold promise for the treatment of NF2-deficient tumors. To test this possibility, we asked if loss of Pak2, a highly expressed group I PAK member, affects the development of malignant mesothelioma in Nf2;Cdkn2a-deficient (NC) mice and the growth properties of NC mesothelioma cells in culture. In vivo, deletion of Pak2 resulted in a markedly decreased incidence and delayed onset of both pleural and peritoneal malignant mesotheliomas in NC mice. In vitro, Pak2 deletion decreased malignant mesothelioma cell viability, migration, clonogenicity, and spheroid formation. RNA-sequencing analysis demonstrated downregulated expression of Hedgehog and Wnt pathway genes in NC;Pak2−/− mesothelioma cells versus NC;Pak2+/+ mesothelioma cells. Targeting of the Hedgehog signaling component Gli1 or its target gene Myc inhibited cell viability and spheroid formation in NC;P+/+ mesothelioma cells. Kinome profiling uncovered kinase changes indicative of EMT in NC;Pak2−/− mesothelioma cells, suggesting that Pak2-deficient malignant mesotheliomas can adapt by reprogramming their kinome in the absence of Pak activity. The identification of such compensatory pathways offers opportunities for rational combination therapies to circumvent resistance to anti-PAK drugs.

Implications:
We provide evidence supporting a role for PAK inhibitors in treating NF2-deficient tumors. NF2-deficient tumors lacking Pak2 eventually adapt by kinome reprogramming, presenting opportunities for combination therapies to bypass anti-PAK drug resistance.
Comparison of bird diversity in protected and non-protected wetlands of western lowland of Nepal
Authors: Adhikari Jagan Nath , Khatiwada Janak Raj , Adhikari Dipendra , Sapkota Suman , Bhattarai Bishnu Prasad , Rijal Deepak , Sharma Lila Nath 
Published: January 2022

Protected areas are considered important for biodiversity conservation, however, studies have shown that habitats outside protected areas can also support high diversity and are important for biodiversity conservation. In this context, we compared the bird diversity between protected (Rani Taal in Shuklaphanta National Park) and non-protected (Sati Karnali Taal) wetlands in western Nepal. Bird surveys were conducted from February to August 2019, using open width point count method in 100 m intervals along transects. A total of 122 species belonging to 18 orders and 44 families were recorded from the protected wetland, and 107 species belonging to 16 orders and 41 families from the non-protected wetland area. Insectivores had high abundance in both wetlands (43% and 47% in protected and non-protected wetlands, respectively). Forest-dependent birds were more abundant in protected wetland compared to non-protected wetland. Our study showed that both protected and non-protected wetlands along with agricultural landscapes, support a richness of birds. Hence priority should be given to both wetlands for the conservation of birds.
Heart Disease and Stroke Statistics—2022 Update: A Report From the American Heart Association
Authors: Tsao Connie W. , Aday Aaron W. , Almarzooq Zaid I. , Alonso Alvaro , Beaton Andrea Z. , Bittencourt Marcio S. , Boehme Amelia K. , Buxton Alfred E. , Carson April P. , Commodore-Mensah Yvonne , Elkind Mitchell S.V. , Evenson Kelly R. , Eze-Nliam Chete , Ferguson Jane F. , Generoso Giuliano , Ho Jennifer E. , Kalani Rizwan , Khan Sadiya S. , Kissela Brett M. , Knutson Kristen L. , Levine Deborah A. , Lewis Tené T. , Liu Junxiu , Loop Matthew Shane , Ma Jun , Mussolino Michael E. , Navaneethan Sankar D. , Perak Amanda Marma , Poudel Remy , Rezk-Hanna Mary , Roth Gregory A. , Schroeder Emily B. , Shah Svati H. , Thacker Evan L. , VanWagner Lisa B. , Virani Salim S. , Voecks Jenifer H. , Wang Nae-Yuh , Yaffe Kristine , Martin Seth S. ,   on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee
Published: January 2022

Background:
The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs).

Methods:
The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2022 Statistical Update is the product of a full year’s worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year’s edition includes data on the monitoring and benefits of cardiovascular health in the population and an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, and the global burden of cardiovascular disease and healthy life expectancy.

Results:
Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics.

Conclusions:
The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.
The Role of Proximity in Technology Dynamics of High-Tech Industries: the Case of Biotechnology and Aviation Industries
Authors: Runiewicz-Wardyn Małgorzata 
Published: January 2022

Abstract
Confronted with new global competitive environment, rising R&D costs, growing integration of different technologies, shorter life cycles, and increased pace of innovation, high-tech companies increasingly collaborate with external partners. Innovation networks became unconditional driver of technological dynamics and growth of high-tech industries. The article aims to explore the role of proximity in innovation networks formation in the two high-tech industries – biotechnology and aviation. Both industries are characterized by different stages of technological maturity, different product life-cycles and development periods, yet both equally depend on highly specialized human capital and collaborative innovation. The article addresses the following research questions: What is the role of proximity – geographical, cognitive, institutional, organizational, social and cultural – in facilitating innovation networks formation in the above mentioned high-tech industries? What type of proximities and the related network externalities assist these industries along their life-cycles? What is the relationship between technology dynamics and innovation networks formation?
Epidemiology of NCAA Track and Field Injuries From 2010 to 2014
Authors: Hopkins Chris , Williams Joel , Rauh Mitchell J. , Zhang Lu 
Published: January 2022

Background: Track and field (T&F) athletes compete in a variety of events that require different skills and training characteristics. Descriptive epidemiology studies often fail to describe event-specific injury patterns. Purpose: To describe the epidemiology of injuries in National Collegiate Athletic Association (NCAA) T&F by sex, setting (practice vs competition), and time of season (indoor vs outdoor) and to compare injury patterns by events within the sport. Study Design: Descriptive epidemiology study. Methods: Data were obtained from the NCAA Injury Surveillance Program for all indoor and outdoor T&F injuries during the academic years 2009-2010 to 2013-2014. Injury rates, injury rate ratios, and injury proportion ratios (IPRs) were reported and compared by sex, injury setting, season, and event. Analysis included time-loss as well as no-time loss injuries. Results: Over the 5 seasons, the overall injury rate was 3.99 injuries per 1000 athletic-exposures (95% CI, 3.79-4.20). After controlling for injury diagnoses, women’s T&F athletes experienced an 18% higher risk of injury (95% CI, 7% to 31%) and missed 41% more time after an injury (95% CI, 4% to 93%) when compared with men. Among all athletes, the injury risk during competition was 71% higher (95% CI, 50% to 95%) compared with practice and required 59% more time loss (95% CI, 7% to 135%). Distance running accounted for a significantly higher proportion of overuse injuries (IPR, 1.70; 95% CI, 1.40-2.05; P < .05) and required 168% more time loss (95% CI, 78% to 304%) than other events. The hip and thigh were the body regions most commonly injured; injury type, however, varied by T&F event. Sprinting accounted for the greatest proportion of hip and thigh injuries, distance running had the greatest proportion of lower leg injuries, and throwing reported the greatest proportion of spine and upper extremity injuries. Conclusion: Injury risk in NCAA T&F varied by sex, season, and setting. Higher injury rates were found in women versus men, indoor versus outdoor seasons, and competitions versus practices. The hip and thigh were the body regions most commonly injured; however, injury types varied by event. These findings may provide insight to programs aiming to reduce the risk of injury and associated time loss in collegiate T&F.
Follow-up of patients with R/R FLT3-mutation–positive AML treated with gilteritinib in the phase 3 ADMIRAL trial
Authors: Perl Alexander E. , Larson Richard A. , Podoltsev Nikolai A. , Strickland Stephen , Wang Eunice S. , Atallah Ehab , Schiller Gary J. , Martinelli Giovanni , Neubauer Andreas , Sierra Jorge , Montesinos Pau , Récher Christian , Yoon Sung-Soo , Hosono Naoko , Onozawa Masahiro , Chiba Shigeru , Kim Hee-Je , Hasabou Nahla , Lu Qiaoyang , Tiu Ramon , Levis Mark J. 
Published: January 2022

Abstract
The phase 3 ADMIRAL (NCT02421939; Study ID: 2215-CL-0301) trial showed superior overall survival in patients with relapsed/refractory FLT3-mutation–positive acute myeloid leukemia (AML) randomized 2:1 to receive the oral FMS-like tyrosine kinase 3 inhibitor gilteritinib vs those randomized to receive salvage chemotherapy (SC). Here we provide a follow-up of the ADMIRAL trial 2 years after the primary analysis to clarify the long-term treatment effects and safety of gilteritinib in these patients with AML. At the time of this analysis, the median survival follow-up was 37.1 months, with deaths in 203 of 247 and 97 of 124 patients in the gilteritinib and SC arms, respectively; 16 gilteritinib-treated patients remained on treatment. The median overall survival for the gilteritinib and SC arms was 9.3 and 5.6 months, respectively (hazard ratio, 0.665; 95% confidence interval [CI], 0.518, 0.853; two-sided P = .0013); 2-year estimated survival rates were 20.6% (95% CI, 15.8, 26.0) and 14.2% (95% CI, 8.3, 21.6). The gilteritinib-arm 2-year cumulative incidence of relapse after composite complete remission was 75.7%, with few relapses occurring after 18 months. Overall, 49 of 247 patients in the gilteritinib arm and 14 of 124 patients in the SC arm were alive for ≥2 years. Twenty-six gilteritinib-treated patients remained alive for ≥2 years without relapse; 18 of these patients underwent transplantation (hematopoietic stem cell transplantation [HSCT]) and 16 restarted gilteritinib as post-HSCT maintenance therapy. The most common adverse events of interest during years 1 and 2 of gilteritinib therapy were increased liver transaminase levels; adverse event incidence decreased in year 2. Thus, continued and post-HSCT gilteritinib maintenance treatment sustained remission with a stable safety profile. These findings confirm that prolonged gilteritinib therapy is safe and is associated with superior survival vs SC. This trial was registered at www.clinicaltrials.gov as #NCT02421939.
Three US Food and Drug Administration–approved therapies for chronic GVHD
Authors: Zeiser Robert , Lee Stephanie J. 
Published: January 2022

Abstract
Chronic graft-versus-host disease (cGVHD) is a major immunologic complication of allogeneic hematopoietic cell transplantation. cGVHD involves multiple organs, reduces quality of life, and often requires prolonged therapy with glucocorticoids, causing severe side effects. After 4 decades of testing multiple therapeutic approaches, ibrutinib, belumosudil, and ruxolitinib were US Food and Drug Administration approved for cGVHD in the last 4 years. Here we put a spotlight on their mechanisms of action, studies that led to approval, and their future role in cGVHD.
A deep learning approach to predict inter-omics interactions in multi-layer networks
Authors: Borhani Niloofar , Ghaisari Jafar , Abedi Maryam , Kamali Marzieh , Gheisari Yousof 
Published: January 2022

AbstractBackgroundDespite enormous achievements in the production of high-throughput datasets, constructing comprehensive maps of interactions remains a major challenge. Lack of sufficient experimental evidence on interactions is more significant for heterogeneous molecular types. Hence, developing strategies to predict inter-omics connections is essential to construct holistic maps of disease.ResultsHere, as a novel nonlinear deep learning method, Data Integration with Deep Learning (DIDL) was proposed to predict inter-omics interactions. It consisted of an encoder that performs automatic feature extraction for biomolecules according to existing interactions coupled with a predictor that predicts unforeseen interactions. Applicability of DIDL was assessed on different networks, namely drug–target protein, transcription factor-DNA element, and miRNA–mRNA. Also, validity of the novel predictions was evaluated by literature surveys. According to the results, the DIDL outperformed state-of-the-art methods. For all three networks, the areas under the curve and the precision–recall curve exceeded 0.85 and 0.83, respectively.ConclusionsDIDL offers several advantages like automatic feature extraction from raw data, end-to-end training, and robustness to network sparsity. In addition, reliance solely on existing inter-layer interactions and independence of biochemical features of interacting molecules make this algorithm applicable for a wide variety of networks. DIDL paves the way to understand the underlying mechanisms of complex disorders through constructing integrative networks.
Resveratrol ameliorates myocardial fibrosis by regulating Sirt1/Smad3 deacetylation pathway in rat model with dilated cardiomyopathy
Authors: Chen Qingquan , Zeng Yu , Yang Xiulin , Wu Yue , Zhang Shuyu , Huang Shirong , Zhong Yameng , Chen Min 
Published: January 2022

Abstract
Background
The aim of this study was to investigate the effects of Resveratrol (RSV) in rats with dilated cardiomyopathy (DCM).

Methods
Porcine cardiac myosin was used to set up rat model with DCM. RSV (10 mg/kg in RSV-L group and 50 mg/kg in RSV-H group) or vehicle was administered to rats with DCM once daily from the 28th day till the 90th day after the first immunization. Cardiac function of rats was evaluated by echocardiographic analysis. The deposition of fibrous tissues in the hearts was evaluated by Masson and picrosirius red staining. The mRNA levels of collagen type I (Col I), collagen type III (Col III) and silence information regulator 1 (Sirt1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The interaction of Sirt1 with Smad3 was revealed by coimmunoprecipitation.

Results
The heart weight, heart weight/body weight ratio, left ventricular end diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) were significantly increased in rats with DCM, and attenuated by RSV. RSV also positively decreased fibrosis, and the expression of Col I and Col III in the myocardium. The Sirt1 mRNA was significantly decreased in myosin-immunized hearts and was positively increased by RSV. The Sirt1 combined with Smad3 directly. Acetylation of Smad3 (Ac-Smad3) was significantly increased in DCM and was markedly decreased by RSV.

Conclusion
RSV effectively ameliorated myocardial fibrosis and improved cardiac function by regulating Sirt1/Smad3 deacetylation pathway in rat model with DCM.
Comparing methods of adenosine administration in paroxysmal supraventricular tachycardia: a pilot randomized controlled trial
Authors: Daengbubpha Phruek , Wittayachamnankul Borwon , Sutham Krongkarn , Chenthanakij Boriboon , Tangsuwanaruk Theerapon 
Published: January 2022

Abstract
Background
Intravenous adenosine is the recommended treatment for paroxysmal supraventricular tachycardia (PSVT). There is no official recommended method of giving adenosine. We compared the success rates between a standard and alternative method of first dose intravenous adenosine in PSVT.

Methods
A pilot parallel randomized controlled study was conducted in the emergency department of a tertiary care hospital. Eligible patients were stable PSVT adult patients. We used block randomization and divided them into two groups, the standard method (double syringe technique of 6 mg of adenosine), and the alternative method (similar to the standard method, then immediately followed by elevating the arm to 90° perpendicular to a horizontal plane for 10 s). The primary outcome was the success rate of electrocardiogram (ECG) response which demonstrated termination of PSVT (at least two-fold of the RR-interval widening or sinus rhythm conversion). Secondary outcomes were complications within one minute after the injection.

Results
We allocated 15 patients in each group and analyzed them as intention-to-treat. The success rate was 86.7% in the alternative group and 80% in the standard group (risk difference 6.7%, 95% confidence interval − 19.9 to 33.2%, P 1.00). Complications within one minute after adenosine injection were also similar in both groups, 14 of 15 patients (93%) in each group had no complications, without significant difference.

Conclusions
No evidence of the difference between alternative and standard methods occurred, in terms of the success rate of ECG response and complications within one minute after adenosine injection. The standard method of adenosine injection is a safe, easy-to-administer, and widely available treatment for PSVT.
Trial Registration: TCTR20200609001.