bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Approved Landing Site (ALS) improves the logistics of interhospital transfer of critically ill patients by helicopter
Authors: van Geffen Geert-Jan , Spoelder Ed J. , Tijben Amanda , Slagt Cornelis 
Published: August 2021

AbstractThe COVID-19 pandemic limited hospital resources and necessitated interhospital transport of ICU-patients in order to provide critical care to all patients in the Netherlands. However, not all hospitals have an approved landing site. The ICU-transport operation was executed under HEMS-license and landing on non-aerodrome terrain was permitted. This allowed the search for an ad-hoc landing site in the direct vicinity of the ICU. The following characteristics were judged: slope, obstacles, size, soil conditions and the presence of foreign objects.Before the start of this transport operation, in two days, all hospitals in the Netherlands were visited and presumed landing sites explored, described, photographed and recorded in the electronic flight bag. At 71 (87,6 %) of the hospitals it was possible to install a temporary approved landing site in the direct vicinity of the ICU. 110 landings were made on these landing sites and 114 landings on approved heliports. Only 11 patients required secondary transport to or from the helicopter landings site. This occurred only in two patients from a heliport to a receiving hospital.The construction of pre-explored approved landing sites in the vicinity of hospitals allows safe transportation of patients by helicopter to hospitals without a heliport.
Systematic assessment of gene co-regulation within chromatin domains determines differentially active domains across human cancers
Authors: Zufferey Marie , Liu Yuanlong , Tavernari Daniele , Mina Marco , Ciriello Giovanni 
Published: August 2021

AbstractBackgroundSpatial interactions and insulation of chromatin regions are associated with transcriptional regulation. Domains of frequent chromatin contacts are proposed as functional units, favoring and delimiting gene regulatory interactions. However, contrasting evidence supports the association between chromatin domains and transcription.ResultHere, we assess gene co-regulation in chromatin domains across multiple human cancers, which exhibit great transcriptional heterogeneity. Across all datasets, gene co-regulation is observed only within a small yet significant number of chromatin domains. We design an algorithmic approach to identify differentially active domains (DADo) between two conditions and show that these provide complementary information to differentially expressed genes. Domains comprising co-regulated genes are enriched in the less active B sub-compartments and for genes with similar function. Notably, differential activation of chromatin domains is not associated with major changes of domain boundaries, but rather with changes of sub-compartments and intra-domain contacts.ConclusionOverall, gene co-regulation is observed only in a minority of chromatin domains, whose systematic identification will help unravel the relationship between chromatin structure and transcription.
Nintedanib downregulates the transition of cultured systemic sclerosis fibrocytes into myofibroblasts and their pro-fibrotic activity
Authors: Cutolo Maurizio , Gotelli Emanuele , Montagna Paola , Tardito Samuele , Paolino Sabrina , Pizzorni Carmen , Sulli Alberto , Smith Vanessa , Soldano Stefano 
Published: August 2021

Abstract
Background
Circulating fibrocytes are an important source of fibroblasts and myofibroblasts, which are involved in fibrotic processes, including systemic sclerosis (SSc).
The study aimed to investigate the effect of nintedanib (a tyrosine kinase inhibitor) in inhibiting the in vitro transition of circulating SSc fibrocytes into myofibroblasts and their pro-fibrotic activity.

Methods
Circulating fibrocytes were obtained from 18 SSc patients and 5 healthy subjects (HSs). Cultured SSc fibrocytes were maintained in growth medium (untreated cells) or treated with nintedanib 0.1 and 1 μM for 3 and 24 h. Fibroblast-specific protein-1 (S100A4) and α-smooth muscle actin (αSMA), as markers of fibroblast/myofibroblast phenotype, together with type I collagen (COL1) and fibronectin (FN), were investigated by qRT-PCR and Western blotting. Non-parametric tests were used for statistical analysis.

Results
Significantly elevated gene and protein expressions of αSMA, S100A4, COL1, and FN were observed in SSc fibrocytes compared to HS fibrocytes (gene: αSMA p < 0.001; others p < 0.0001; protein: all p < 0.05). Interestingly, an increased gene and protein expression of αSMA and S100A4 was found in fibrocytes from SSc patients positive for anti-Scl70 and with interstitial lung disease (ILD) (Scl70+ILD+) compared to Scl70−ILD− patients (S100A4: gene: p < 0.01; protein: p < 0.05), whereas no differences were observed for COL1 and FN.
Nintedanib reduced gene and protein expression of αSMA, S100A4, COL1, and FN in SSc fibrocytes compared to untreated ones with different statistical significance.
Noteworthy, nintedanib significantly downregulated gene and protein expression of αSMA, S100A4, COL1, and FN in Scl70+ILD+ fibrocytes (all p < 0.05), whereas only that of S100A4 and FN was significantly downregulated (p < 0.05) in Scl70−ILD− fibrocytes compared to the related untreated cells.

Conclusions
Nintedanib seems to downregulate in vitro the transition of fibrocytes into myofibroblasts and their pro-fibrotic activity, particularly in cells isolated from Scl70+ILD+ SSc patients.
Primary leiomyoma of the ureter: a case report
Authors: Morinaga Shingo , Aoki Shigeyuki , Tobiume Motoi , Nishikawa Genya , Muramatsu Hiroyuki , Tsuzuki Toyonori , Saiki Reiko , Hashimoto Junko , Mori Kaori , Yamaguchi Yoko , Kobayashi Akari , Sawada Tomoko , Futamachi Ruriko , Yamada Yoshiaki 
Published: August 2021

Abstract
Background
Only 14 cases of leiomyoma with ureteral origin have been reported previously. Such primary leiomyomas often present as hydronephrosis, making the diagnosis difficult. Radical nephroureterectomy is often performed because of the possible diagnosis of a malignant tumor. We report the 15th case of primary leiomyoma with a ureteral origin.

Case presentation
A 51-year-old Japanese man presented with a chief complaint of asymptomatic gross hematuria with a history of hypertension. Enhanced computed tomography showed a tumor at the upper part of the right ureter that appeared to be the cause of hydronephrosis and contracted kidney; no retroperitoneal lymphadenopathy and distal metastasis were observed. A well-defined 20-mm (diameter) defect was identified at the upper of the right ureter on retrograde pyelogram with no bladder cancer on cystoscopy. Urine cytology and right divided renal urine cytology findings were negative. Laparoscopic nephroureterectomy was performed, and the extracted tumor measured 20 × 13 mm. Histopathological examination revealed primary leiomyoma with no recurrence 16 months after the operation.

Conclusions
Preoperative examination with the latest available ureteroscopic technology can help preserve renal function in the case of benign tumors by enabling preoperative ureteroscopic biopsy or intraoperative rapid resection. Moreover, nephroureterectomy is recommended in the case of preoperative suspicion of ureteral malignant tumors.
Validation of an optimized HPLC–UV method for the quantification of formononetin and biochanin A in Trifolium pratense extract
Authors: Lee Ju Sung , Paje Leo Adrianne , Kim Min Jeong , Jang Seung Hee , Kim Jong Tae , Lee Sanghyun 
Published: August 2021

AbstractHere, two important isoflavones present in Trifolium pratense, formononetin and biochanin A, were analyzed by high performance liquid chromatography coupled with UV (HPLC–UV). These isoflavones are marker compounds with anti-inflammatory, anti-cancer, and anti-oxidant properties, and are also potent phytoestrogens that can be used in hormonal therapies. Till date, no study regarding rapid identification and quantification of T. pratense extract has been conducted. This study developed and validated an optimized method for quantifying formononetin and biochanin A using HPLC–UV. The results showed excellent linearity of the calibration curve (r2 ≥ 0.999), and good resolutions of chromatographic peaks were obtained. Other validation parameters such as specificity, accuracy, and precision demonstrated that our method had good reliability and sensitivity. Furthermore, our method for quantifying formononetin and biochanin A in T. pratense extract is convenient.
Study on the Fracture Toughness of Polypropylene–Basalt Fiber-Reinforced Concrete
Authors: Liang Ninghui , Ren Lianxi , Tian Shuo , Liu Xinrong , Zhong Zuliang , Deng Zhiyun , Yan Ru 
Published: August 2021

AbstractTo study the hybrid effects of polypropylene fiber and basalt fiber on the fracture toughness of concrete, 13 groups of notched concrete beam specimens with different fiber contents and mass ratios were prepared for the three-point bending test. Based on acoustic emission monitoring data, the initiation cracking load and instability load of each group of specimens were obtained, and the fracture toughness parameters were calculated according to the double-K fracture criterion. The test results show that the basalt fiber-reinforced concrete has a greater increase in initial fracture toughness, and the toughness of coarse polypropylene fiber-reinforced concrete is more unstable. Moreover, after the coarse polypropylene fiber content reaches 6 kg/m3 and the basalt fiber content reaches 3 kg/m3, increasing the content will not significantly improve the fracture toughness of the concrete. The polypropylene–basalt fiber will produce positive and negative effects when mixed, and the mass ratio of 2:1 was optimal. Finally, the fitting analysis revealed that the fracture process of polypropylene–basalt fiber-reinforced concrete (PBFRC) can be objectively described by the bilinear softening constitutive curve improved by Xu and Reinhardt.
Diagnostic value of median nerve shear wave ultrasound elastography in diagnosis and differentiation of carpal tunnel syndrome severity
Authors: Ibrahim Heba Refaat 
Published: August 2021

AbstractBackgroundCarpal tunnel syndrome (CTS) is the commonest type of peripheral nerve entrapment syndromes. The study aimed at evaluation of diagnostic value of median nerve stiffness measured by shear wave ultrasound elastography for diagnosis and differentiation of CTS severity, correlated to electrophysiological studies. This case–control study involved 40 patients (56 wrists) with CTS of different severity and 40 controls (40 wrists). All participants underwent electrophysiological study to assess the CTS severity, high-resolution conventional B-mode ultrasound to assess cross-sectional area “CSA” of median nerve at carpal tunnel, ratio of median nerve CSA at carpal tunnel and forearm, and shear wave ultrasound elastography with measurement of median nerve mean stiffness and correlation to electrophysiological results as the reference standard.ResultsMean median nerve stiffness by shear wave US elastography was increased in patients with CTS compared to controls and across the different CTS severity groups (Pvalue < 0.001 & 0.001, respectively). The cutoff value by ROC curve analysis for median nerve stiffness to differentiate between patients with CTS and control group was 65.4 kPa (Pvalue < 0.001, 94.6% sensitivity, 97.3% specificity). Higher diagnostic accuracy was noted with the combination of shear wave elastography and conventional B-mode US with improved AUC (B-mode + shear wave; 0.962,Pvalue < 0.001).ConclusionsShear wave ultrasound elastography of median nerve was able to discriminate different severity subgroups of CTS with high sensitivity, while conventional US couldn’t. The diagnostic accuracy of CTS was improved when combined high-resolution conventional B-mode US and complementary shear wave ultrasound elastography.
A review on importance of bioactive compounds of medicinal plants in treating idiopathic pulmonary fibrosis (special emphasis on isoquinoline alkaloids)
Authors: Dudala Sai Sushma , Venkateswarulu T. C. , Kancharla Sushma Chandulee , Kodali Vidya Prabhakar , Babu D. John 
Published: August 2021

Abstract
Background
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown cause which disrupts the normal lung architecture and functions by deregulating immune responses and ultimately leads to the death of the individual. A number of factors can lead to its development and currently there is no cure for this disease.

Main text
There are synthetic drugs available to relieve the symptoms and decelerate its development by targeting pathways involved in the development of IPF, but there had also been various side effects detected by their usage. It is known since decades that medicinal plants and their compounds have been used all over the world in natural medicines to cure various diseases. This review article is focused on the effects of various natural bioactive compounds of 26 plant extracts that show prophylactic and therapeutic properties against the disease and so can be used in treating IPF replacing synthetic drugs and reducing the side effects.

Short conclusion
This review includes different mechanisms that cause pulmonary fibrosis along with compounds that can induce fibrosis, drugs used for the treatment of pulmonary fibrosis, diagnosis, the biochemical tests used for the experimental study to determine the pathogenesis of disease with a special note on Isoquinoline alkaloids and their role in reducing various factors leading to IPF thus providing promising therapeutic approach.
Experience in endoscopic stapedotomy technique and its audiological outcome: a case series
Authors: Abdullah Nazik E. , Nafie Tarig A. , Mohammed Ahmed F. , Abdelmomin Alwaleed A. , Yagi Hashim I. , Ahmed Azza M. 
Published: August 2021

Abstract
Background
Stapedotomy is being performed endoscopically for otosclerosis in Sudan since 2011 with increasing number of patients. This prospective hospital-based study from Nov 2016 to Nov 2020 states the clinic-demographic features of otosclerosis; it describes this surgical technique and hearing outcome following endoscopic stapedotomy.

Results
Total number included in the study was 91 patients. Females were 48, and males were 43 with a female to male ratio of 1.1:1. Age ranged from 19 years to 52 with a mean age of 30.6± 7 SD years. The main symptom was decreased hearing in all patients (100%); in 82 patients (90%), it was bilateral, followed by tinnitus in 80 patients (88%) while two patients (2.2%) had vertigo. Family history was stated by 2 patients (2.2%) only. Audiological assessment by pure tone audiogram (PTA) for each ear (total of 182) revealed that conductive hearing loss (CHL) is the commonest type of hearing loss in 148 ears (81.3%), mixed type in 30 ears (16.5%), while 4 ears (2.2%) were normal.
Endoscopic stapedotomy was performed for 74 patients; this technique was safe; few complications were managed successfully: one gusher and one revision, with no facial nerve injury. Majority of complications happened during the first year. Mean air bone gap (ABG) gain was 23.3± 7.2 dB, air conduction (AC) gain was 18.3 ± 8 dB, and Carhart notch disappeared in 79.5%.

Conclusions
Endoscopic stapedotomy is a safe and effective procedure with a steep learning curve and a satisfactory hearing outcome. The air bone gap (ABG) gain was comparable to international studies.
Effect of COVID-19 pandemic on mental health hospital admissions: comparative population-based study
Authors: Bonello Fabian , Zammit Daniela , Grech Anton , Camilleri Victoria , Cremona Rachel 
Published: August 2021

Background
The coronavirus disease 2019 (COVID-19) global pandemic caused mental health services to be downscaled to abide by the public health restrictions issued.

Aims
The aim of this study was to investigate whether the pandemic and resultant restrictions had an impact on Malta's admissions to hospital for mental health issues by assessing the number and nature of psychiatric admissions to our only national mental health hospital.

Method
Data collection was carried out retrospectively for the 13-week period between 7 March 2020 and 4 June 2020, compared with the equivalent in 2019. Demographic data was obtained and descriptive statistical analysis through the use of the χ²-test, z-test and logistic regression model were used to compare both data-sets, using a P-value of 0.05.

Results
An overall reduction in admissions to hospital was noted in 2020 when compared with 2019, recorded to be lowest in March 2020 with a steady acceleration of admissions up until May 2020 (χ2(3) = 22.573, P < 0.001). This coincided with a decelerated rate of positive COVID-19 cases locally. In 2020, there were significantly higher female admissions (χ2(1) = 10.197, P < 0.001), increased presentations of self-harm/suicidal ideation (P < 0.001) and higher involuntary admissions using the Mental Health Act (χ2(1) = 4.904, P = 0.027). The logistic regression model identified total length of stay in hospital, primary mental health diagnosis, gender and month of admission as variables significantly associated with an admission.

Conclusions
Our first population-wide study confirms that the COVID-19 pandemic and subsequent public health restrictions had an impact on the population's hospital admissions for mental health issues.
Management Approach to Acute Myeloid Leukemia Leveraging the Available Resources in View of the Latest Evidence: Consensus of the Saudi Society of Blood and Marrow Transplantation
Authors: Alahmari Bader , Alzahrani Mohsen , Al Shehry Nawal , Tawfiq Osamah , Alwasaidi Turki , Alhejazi Ayman , Bakkar Mohammed , Al Behainy Amal , Radwi Mansour , Alaskar Ahmed 
Published: August 2021

PURPOSE Acute myeloid leukemia (AML) is the most prevalent acute leukemia in adults and is responsible for the majority of cancer-related mortality. In Saudi Arabia, leukemia is ranked the fifth most prevalent type of malignancy in adults. Our aim is to review existing epidemiologic data in Saudi Arabia and develop consensus guidelines for management of AML. METHODS We review literature related to AML epidemiology, treatment patterns, and outcomes in Saudi Arabia, as well as literature related to the current advances in AML treatment. A panel of 10 experts from eight institutions in Saudi Arabia reviewed the literature and developed a consensus statement. RESULT We provide an update of the available AML epidemiologic data in Saudi Arabia and describe recent developments in the diagnostic workup, risk stratification, and treatment algorithm. The consensus recommendations for the management of AML in Saudi Arabia were developed. CONCLUSION The recommendations are in parallel with the recent international guidelines for the diagnosis and management of AML.
Randomized Phase II Trial of Vincristine-Irinotecan With or Without Temozolomide, in Children and Adults With Relapsed or Refractory Rhabdomyosarcoma: A European Paediatric Soft Tissue Sarcoma Study Group and Innovative Therapies for Children With Cancer Trial
Authors: Defachelles Anne-Sophie , Bogart Emilie , Casanova Michela , Merks Johannes H. M. , Bisogno Gianni , Calareso Giuseppina , Gallego Melcon Soledad , Gatz Susanne Andrea , Le Deley Marie-Cécile , McHugh Kieran , Probst Alicia , Rocourt Nathalie , van Rijn Rick R. , Wheatley Keith , Minard-Colin Véronique , Chisholm Julia C. 
Published: August 2021

PURPOSEThe VIT-0910 trial was conducted to evaluate efficacy and safety of the vincristine-irinotecan combination with and without temozolomide (VIT and VI, respectively) in relapsed or refractory rhabdomyosarcoma (RMS).METHODSIn this randomized European phase II trial, patients age 0.5-50 years received 21-day cycles combining vincristine (1.5 mg/m2once a day on day 1 and day 8) and irinotecan (50 mg/m2once a day from day 1 to day 5) with and without temozolomide (125 mg/m2once a day from day 1 to day 5 and 150 mg/m2once a day from cycle 2), until progression or unacceptable toxicity. The primary end point was objective response rate after two cycles. Secondary end points included best response, progression-free survival, overall survival, and adverse events. A Simon 2-stage design was initially planned to separately analyze 40 patients/arm. After amendment, the trial sample size was increased to 120 and a comparison between arms, adjusted for confounding factors, was added to the statistical plan (ClinicalTrials.gov, NCT01355445 ).RESULTSOverall, 120 patients (60 per arm) were recruited in 37 European centers. The median age was 11 years (range, 0.75-45); 89% of patients had a relapsed RMS. The objective response rate was 44% (24 of 55 evaluable patients) for VIT versus 31% (18 of 58) for VI (adjusted odds ratio, 0.50; 95% CI, 0.22 to 1.12; P = .09). The VIT arm achieved significantly better overall survival (adjusted hazard ratio, 0.55; 95% CI, 0.35 to 0.84; P = .006) compared with VI, with consistent progression-free survival results (adj-hazard ratio, 0.68; 95% CI, 0.46 to 1.01; P = .059). Overall, patients experienced adverse events ≥ grade 3 more frequently with VIT than VI (98% v 78%, respectively; P = .009), including a significant excess of hematologic toxicity (81% v 61%; P = .025).CONCLUSIONThe addition of temozolomide to VI improved chemotherapy efficacy for patients with relapsed RMS, with manageable increase in toxicity. VIT is considered the new standard treatment in these patients in the European paediatric Soft Tissue Sarcoma Group and will be the control arm in the next randomized trial.
Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study
Authors: Kang Yoon-Koo , George Suzanne , Jones Robin L. , Rutkowski Piotr , Shen Lin , Mir Olivier , Patel Shreyaskumar , Zhou Yongjian , von Mehren Margaret , Hohenberger Peter , Villalobos Victor , Brahmi Mehdi , Tap William D. , Trent Jonathan , Pantaleo Maria A. , Schöffski Patrick , He Kevin , Hew Paggy , Newberry Kate , Roche Maria , Heinrich Michael C. , Bauer Sebastian 
Published: August 2021

PURPOSE Primary or secondary mutations in KIT or platelet-derived growth factor receptor alpha ( PDGFRA) underlie tyrosine kinase inhibitor resistance in most GI stromal tumors (GISTs). Avapritinib selectively and potently inhibits KIT- and PDGFRA-mutant kinases. In the phase I NAVIGATOR study ( NCT02508532 ), avapritinib showed clinical activity against PDGFRA D842V–mutant and later-line KIT-mutant GIST. VOYAGER ( NCT03465722 ), a phase III study, evaluated efficacy and safety of avapritinib versus regorafenib as third-line or later treatment in patients with unresectable or metastatic GIST. PATIENTS AND METHODS VOYAGER randomly assigned patients 1:1 to avapritinib 300 mg once daily (4 weeks continuously) or regorafenib 160 mg once daily (3 weeks on and 1 week off). Primary end point was progression-free survival (PFS) by central radiology per RECIST version 1.1 modified for GIST. Secondary end points included objective response rate, overall survival, safety, disease control rate, and duration of response. Regorafenib to avapritinib crossover was permitted upon centrally confirmed disease progression. RESULTS Four hundred seventy-six patients were randomly assigned (avapritinib, n = 240; regorafenib, n = 236). Median PFS was not statistically different between avapritinib and regorafenib (hazard ratio, 1.25; 95% CI, 0.99 to 1.57; 4.2 v 5.6 months; P = .055). Overall survival data were immature at cutoff. Objective response rates were 17.1% and 7.2%, with durations of responses of 7.6 and 9.4 months for avapritinib and regorafenib; disease control rates were 41.7% (95% CI, 35.4 to 48.2) and 46.2% (95% CI, 39.7 to 52.8). Treatment-related adverse events (any grade, grade ≥ 3) were similar for avapritinib (92.5% and 55.2%) and regorafenib (96.2% and 57.7%). CONCLUSION Primary end point was not met. There was no significant difference in median PFS between avapritinib and regorafenib in patients with molecularly unselected, late-line GIST.