bluuebunny/crossref_metadata_2025 huggingface dataset:
Can paraspinal muscle degeneration be a reason for refractures after percutaneous kyphoplasty? A magnetic resonance imaging observation
Authors: Zhao He , He Yan , Yang Jun-Song , Bao Wei , Chen Jian , Liu Ji-Jun , Li Qing-Da , Liu Peng , Qian Bing , Zhao Yuan-Ting , Hao Ding-Jun
Published: August 2021

Background

Vertebral augmentation (VA) techniques are used to treat acute osteoporotic vertebral compression fractures (OVCFs). However, the incidence of recurrent vertebral fractures after VA is controversial. Various factors have been discussed in the literature, but no convincing study on the quality of paraspinal muscles has been reported. The purposes of this study were to evaluate the changes in paraspinal muscles and discuss the relationship between paraspinal muscle degeneration and vertebral refractures after percutaneous kyphoplasty (PKP).

Methods

This retrospective study was conducted in patients who underwent PKP for an initial OVCF between July 2017 and August 2018. Patients were followed up and categorized in the refractured or non-refractured group. A final magnetic resonance imaging (MRI) scan and a preoperative MRI scan were used to determine the measurements. The paraspinal muscles at the mid-height level of the initial fractured vertebral body were measured using regions of interest (ROIs), including the cross-sectional area (CSA) and signal intensity (SI). The changes in the observed data were compared between the groups using rank-sum tests.

Results

Overall, 92 patients were enrolled in the study; 33 of them sustained vertebral refractures during the follow-up and the other 59 patients did not. There were no significant differences in terms of sex, age, preoperative bone mineral density, and body mass index between the groups (all, P > 0.05). The refractured group had a significantly higher decrease in the ROI-CSA and CSA/SI, and a higher increase in ROI-SI, compared with the preoperative data (all, P < 0.05).

Conclusions

The quality of paraspinal muscles significantly decreased in patients with new OVCFs after PKP. This brings a new perspective to the study of postoperative recurrent fractures; patients and physicians need to pay more attention to the efficacy of bed rest and bracing.
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

The 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

Background

Spatial 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.

Result

Here, 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.

Conclusion

Overall, 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

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

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

Here, 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

To 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

Background

Carpal 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.

Results

Mean 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).

Conclusions

Shear 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

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

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.
Toward autonomous event identification in wave-equation traveltime inversion
Authors: Chen Fuqiang , Peter Daniel
Published: August 2021

We have developed a method to automatically relate events between observed and synthetic data for wave-equation traveltime (WT) inversion. The scheme starts with local similarity measurements by applying crosscorrelation to localized traces. We then develop a differentiable alternative for the argmax function. By applying the differentiable argmax to each time slice of the local similarity map, we build a traveltime difference function but keep this process differentiable. WT inversion requires only the traveltime difference of related events through a phase shift. Thus, we must reject events that are not apparently related between observed and synthetic data. The local similarity map implies the possibility of doing so but indicates abrupt changes with time and offset. To mitigate this problem, we have introduced a dynamic programming algorithm to define a warping function. Wave packets in the observed and synthetic data are assumed to be related if they are connected by this warping function and if they exhibit high local similarity. Only such related events are considered in the subsequent calculation of misfit and adjoint source. Numerical examples demonstrate that our method successfully retrieves an informative model from roughly selected data. In contrast, WT inversion based on crosscorrelation or deconvolution fails to do so.
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

PURPOSE

The 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).

METHODS

In 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 ).

RESULTS

Overall, 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).

CONCLUSION

The 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.
Nuclear translocation of the tagged endogenous MAPK MPK-1 denotes a subset of activation events in C. elegans development
Authors: Rasmussen Neal R. , Reiner David J.
Published: August 2021

The extracellular signal-regulated kinases (ERKs) are mitogen-activated protein kinases (MAPKs) that are utilized downstream of Ras to Raf to MEK signaling to control activation of a wide array of targets. Activation of ERKs is elevated in Ras-driven tumors and RASopathies, and thus is a target for pharmacological inhibition. Regulatory mechanisms of ERK activation have been studied extensively in vitro and in cultured cells, but little in living animals. In this study, we tagged the Caenorhabditis elegans ERK-encoding gene, mpk-1. MPK-1 is ubiquitously expressed with elevated expression in certain contexts. We detected cytosol-to-nuclear translocation of MPK-1 in maturing oocytes and hence validated nuclear translocation as a reporter of some activation events. During patterning of vulval precursor cells (VPCs), MPK-1 is necessary and sufficient for the central cell, P6.p, to assume the primary fate. Yet MPK-1 translocates to the nuclei of all six VPCs in a temporal and concentration gradient centered on P6.p. This observation contrasts with previous results using the ERK nuclear kinase translocation reporter of substrate activation, raising questions about mechanisms and indicators of MPK-1 activation. This system and reagent promise to provide critical insights into the regulation of MPK-1 activation within a complex intercellular signaling network.
Tissue clearing and 3D imaging – putting immune cells into context
Authors: Hofmann Julian , Keppler Selina J.
Published: August 2021

A better understanding of cell–cell and cell–niche interactions is crucial to comprehend the complexity of inflammatory or pathophysiological scenarios such as tissue damage during viral infections, the tumour microenvironment and neuroinflammation. Optical clearing and 3D volumetric imaging of large tissue pieces or whole organs is a rapidly developing methodology that holds great promise for the in-depth study of cells in their natural surroundings. These methods have mostly been applied to image structural components such as endothelial cells and neuronal architecture. Recent work now highlights the possibility of studying immune cells in detail within their respective immune niches. This Review summarizes recent developments in tissue clearing methods and 3D imaging, with a focus on the localization and quantification of immune cells. We first provide background to the optical challenges involved and their solutions before discussing published protocols for tissue clearing, the limitations of 3D imaging of immune cells and image analysis. Furthermore, we highlight possible applications for tissue clearing and propose future developments for the analysis of immune cells within homeostatic or inflammatory immune niches.
Single motherhood, social independence and non-communicable disease (NCD) outcomes among young females (15-24 years old) in South Africa
Authors: De Wet-Billings Nicole
Published: August 2021

Background: Non-communicable diseases (NCDs) acquired during youth follow into and affect adulthood. The association between young mother’s social independence and NCD status is of policy interest due to its effect on economic and social development. This study aimed to determine the causal relationship between social independence and NCD outcomes among young, single mothers in South Africa.

Methods: Data from the South African National Income Dynamics Survey (NIDS) in 2008 and 2017 was used to determine if single mothers developed hypertension, diabetes or asthma by various indicators of social independence, including highest level of education and employment status. The sample was initially made-up of unmarried females (15-24 years old) without any children in 2008. Both fertility and social independence was followed-up to 2017.

Results: In total, 66 young females developed an NCD by 2017 and 87% (n=57) of these women had a child in the interim period. Employment of young females increased from 4.78% in 2008 to 37.79% in 2017, but completion of secondary or tertiary education declined from 67.94% in 2008 to 56.01% in 2017. In addition, half (50.88%) of the young females were partially independent by 2017, with only 11.03% being fully independent at this time. Finally, logistic regression results showed that the likelihood of developing an NCD increased if young females with children were not socially independent.

Conclusions: The relationship between social independence and NCDs suggest that policies and programmes in South Africa need to incorporate socioeconomic status as a determinant of disease and in particular, need to address socioeconomic indicators as additive measures and not autonomous indicators.
EFFICIENCY OF THE MODIFIED FERTILIZER AND MICROBIOLOGICAL PREPARATION ON SPRING BARLEY IN THE CONDITIONS OF THE FOREST-STEPPE OF THE VOLGA REGION
Authors: Saydyasheva Galina , Zayceva Kseniya
Published: August 2021

Studies to determine the effect of mineral, biomineral fertilizers and biological products on the content of nutrients (nitrogen, phosphorus and potassium) during the growing season in spring barley plants were carried out in 2015-2017 on leached heavy loam chernozem of Ulyanovsk region. The soil of the experimental site contained: humus 6.43...6.62 % (according to Tyurin), total nitrogen-0.26 % (according to Kjeldahl), mobile phosphorus and potassium-214 ... 228 and 101...117 mg/kg of soil, respectively (according to Chirikov), pHKCl – 6.3...6.8 (GOST 26483-85), hydrolytic acidity – 1.20...1.29 mmol/100 g of soil (according to Kappen).

The scheme of the experiment included the following options: without fertilizers (control); Bisolbiphite (seed inoculation); N15P15K15 (regular azofoska); N15P15K15m (azofoska modified with BisolbiPhite); N7,5P7,5K7,5m (azofoska modified with BisolbiPhite in a half dose). We used a complex mineral fertilizer-azofoska in a dose of 15 kg d. v. per 1 ha of nitrogen, phosphorus and potassium and a microbiological preparation BisolbiFit, which serves as a modifier of seeds and mineral fertilizers. The drug is based on a strain of bacteria of the rhizosphere Bacillus subtilis H-13, isolated from chernozem soil. Inoculation of spring barley seeds with a biological preparation was carried out 1...2 days before sowing (400...600 g/t of seeds), mineral fertilizer was treated on the day of its application to the soil (4 kg/t of fertilizers). As the studied crop, the variety of spring barley Nutans 553, zoned in Ulyanovsk region, was sown on experimental plots. Mineral fertilizers and biological preparation had a positive effect on the nutrient content of spring barley plants. Under the influence of the studied fertilizer, the nitrogen content in the green mass of barley increased by 0.09...0.30%, phosphorus − by 0.09...0.18%, potassium-by 0.25...1.10 %, in relation to the variant where mineral fertilizer and microbiological preparation were not used. As a result of the correlation analysis, a positive relationship was established between the yield of barley and the content of nutrients in plants during the tillering, tubing and flowering phases: with nitrogen (r = 0.78; 0.83; 0.75), phosphorus (r = 0.80; 0.42; 0.71) and potassium (r = 0.66; 0.59; 0.91). As a result of this research work, it was found that the use of the studied fertilizers and the biological product BisolbiFit positively affected the content of the main nutrients (nitrogen, phosphorus and potassium) in spring barley plants in all phases of its development.
Identity and the learning experience of non-traditional students undertaking the specialist practitioner qualification
Authors: Thirtle Sarah
Published: August 2021

This small qualitative study is an exploration of the concept of identity and its relationship to the learning experience of non-traditional students undertaking the Specialist Practitioner Qualification in District Nursing. Using a narrative inquiry approach, three participants were asked to recall their experiences 1 year after completing the SPQDN programme. Individual narratives were analysed, and central themes were extracted using NVivo coding. The findings indicated that feelings of academic self-doubt, the impact of past learning experiences and the connotations of being labelled as a student all had an influence on the participants' learning experience.
Management of work stress and burnout among community nurses arising from the COVID-19 pandemic
Authors: While Alison E , Clark Louise L
Published: August 2021

The COVID-19 pandemic has increased workload demands for many NHS staff including those working in the community. Nurse managers can make a difference by being authentic leaders, nurturing a supportive organisation where the workload is managed participatively and self-kindness is legitimate. Unfortunately some staff may experience burnout and this article presents a personal management plan to address the symptoms of burnout and aid recovery, although it cannot promote a total recovery if the cause of the symptoms remains unaddressed.
Lessons learnt from the MS Trust Conference 2021
Authors: Thomas Del
Published: August 2021

February 2021 marked the first virtual conference held by the MS Trust. Del Thomas outlines the vital learnings from the event and the importance of connecting—albeit virtually—with friends and colleagues in the field.
Anti-spasticity medication and multiple sclerosis: why nurses and therapists need to get involved
Authors: Hendrie Wendy , Dorsey-Campbell Rachel
Published: August 2021

Spasticity is common in people with MS and can negatively affect activities of daily living and quality of life. It can be managed with anti-spasticity medications, but prescribers often fail to titrate, monitor or review the efficacy of these drugs. Optimal doses are not always reached, and insidious side effects can cause symptoms that mimic disease progression, increase disability and hinder therapeutic interventions. It is important that health professionals involved in the management of people with MS are aware of the injurious potential of these medications and educate people with MS to self-manage them. This article looks at common anti-spasticity medications, the mode of action, dosage and side effects. It provides examples of how medication misuse can lead to increased disability and explains how neurological nurses and physiotherapists can play an active role in monitoring these medications as part of their treatment plan, including information on becoming an independent or supplementary prescriber.
A new energy in multiple sclerosis nursing
Authors: Whisker Emily
Published: August 2021

The UK Multiple Sclerosis Specialist Nurse Association pulls together with a new energy on developing projects for 2021, initiating recovery from the impact of COVID-19 on multiple sclerosis (MS) nursing services. Developing an MS specialist nurse competency document is at the forefront of the association's work, to aid sustainability and growth within the workforce. Emily Whisker elaborates.
Influence of tolerance to uncertainty on personal and professional development of pilots during aviation specialists’ training
Authors: LUZIK Elvira V. , DEMCHENKO Nataliia I. , MELNYK Nataliia I. , SEMICHENKO Valentina A. , PROSKURKA Nataliіa M.
Published: August 2021

The application of a new pragmatic educational model in the information environment of the higher technical education institution, which corresponds to the innovative and perspective model of society development, determined the transition from the process approach in the organisation of professional training of future aviation specialists to a reflective and effect–oriented one. It forms the basis of training objectives related to providing the country with specialists in aviation industry. The aim of the study is to theoretically substantiate, develop and experimentally test the effectiveness of the professional training model for future specialists under the conditions of uncertainty of the educational process of higher education institutions on the basis of a reflective approach. The result of the experimental stage of the study, as the foundation of the personal and professional development of the student, confirmed the effectiveness of the model based on the reflective approach. The systemically important core of the study considered the goals and results implemented in the educational and informational environment of the National Aviation University with the help of appropriately constructed psychological and pedagogical conditions, which were implemented at each stage of professional training with the innovative educational technologies.
Economic feasibility of modifications to the design of transport aircraft
Authors: IGNATYEVS Sergeys , MAKUSHKIN Sergey A. , SPIVAKOVSKYY Sergiy
Published: August 2021

The relevance of the subject matter is conditioned by the need to fully justify the implementation of modifications to the structures of transport aircraft from an economic standpoint, in order to save money during their construction and improve the functioning of the system for planning further design developments in this line. The purpose of this study is to establish a coherent model of the economic feasibility of aircraft modifications, which allows effectively solving the issues of cost savings in their design and subsequent launch into mass production and operation. The leading approach in this study is a combination of analytical research of the issues of transport aircraft modification with empirical research of the economic feasibility of such measures, in the context of creating a coherent concept of the need for a set of measures to improve the structure of air transport. The findings indicate the presence of a clear relationship between a wide range of parameters that determine the indicators of economic feasibility of modernizing transport aircraft, as well as significant economic advantages of a high-quality modification of the aircraft design.
Deep circulation in the Lau Basin and Havre Trough of the western South Pacific Ocean from floats and hydrography
Authors: Simons Elizabeth , Speer Kevin , Thurnherr Andreas M.
Published: August 2021

A system of meridional ridges in the western South Pacific Ocean frame the Lau Basin and Havre Trough, and form a barrier to direct communication between the far western South Pacific basins and the interior South Pacific Ocean. The eastern side of this system comprises the Tonga and
Kermadec Ridges, the location of the main deep western boundary current entering the Pacific Ocean. Observations from floats released in the Lau Basin as part of the RIDGE2000 program suggested the presence of a western boundary current along the Lau Ridge exiting into the North Fiji Basin.
Those observations, together with Argo sub-surface float data and repeat hydrographic sections, confirm and expand the boundary current observations along the Lau Ridge throughout the Lau Basin and into the Havre Trough, along the Colville Ridge. The observations also reveal two previously
unrecognized westward flowing jets bisecting the Lau Basin and Havre Trough. Using an extension to the classic Stommel-Arons abyssal circulation model, the predicted strength and location of these boundary currents and their bifurcation is compared with the float observations. The model provides
a simplified view of the dynamics controlling the boundary current structure in the deep basins. A comparison of transport within the western boundary current derived from float data, hydrographic sections, and the idealized analytical model indicates that roughly 4 Sv (below 1,000 db) is
transported northward through the Lau Basin, exiting into the North Fiji Basin.
TSRRNet: two-stage reflection removal network with reflective guidance
Authors: Cheng Kuanhong , Du Juan , Li Jia , Qian Kun , Wang Zhixiao
Published: August 2021

Due to the shortage of paired images, the training of reflection
removal networks relies heavily on synthesized samples, for which the
ground truths of transmission and reflection are both known. But most
existing CNN-based models cannot fully utilize the reflection
information, which may cause performance limitations. In this paper,
our goal is to design a novel, to the best of our knowledge, network
that can take the reflection layer to refine the transmission layer.
To this end, we propose a two-stage
generative-adversarial-network-based network, where the first stage is
used to obtain the coarse estimation of transmission and reflection,
and the second stage is used to achieve the refinement. In addition,
instead of just applying two penalty terms on the two coarse
predictions in previous works, we consider the coarse reflection as a
soft mask overlapped on the transmission and apply the recently
proposed gated convolution into the second stage for further
refinement. The network is trained with an adversarial frame using
WGAN. The experimental results with benchmark datasets indicate that
our method outperforms several state-of-the-art networks.
Genetic source tracking of human plague cases in Inner Mongolia-Beijing, 2019
Authors: Li Jianyun , Wang Yumeng , Liu Fang , Shen Xiaona , Wang Yiting , Fan Mengguang , Peng Yao , Wang Shuyi , Feng Yilan , Zhang Wen , Lv Yanning , Zhang Huijuan , Lu Xin , Zhang Enmin , Wei Jianchun , Chen Lijuan , Kan Biao , Zhang Zhongbing , Xu Jianguo , Wang Wenrui , Li Wei
Published: August 2021

On 12 November 2019, one couple from the Sonid Left Qi (County) in the Inner Mongolia Autonomous Region was diagnosed with pneumonic plague in Beijing. The wife acquired the infection from her husband. Thereafter, two bubonic plague cases were identified in Inner Mongolia on November 16th and 24th. In this study, genome-wide single nucleotide polymorphism (SNP) analysis was used to identify the phylogenetic relationship of Yersinia pestis strains isolated in Inner Mongolia. Strains isolated from reservoirs in 2018 and 2019 in Inner Mongolia, together with the strain isolated from Patient C, were further clustered into 2.MED3m, and two novel lineages (2.MED3q, 2.MED3r) in the 2.MED3 population. According to the analysis of PCR-based molecular subtyping methods, such as the MLVA 14 scheme and seven SNP allele sequencing, Patients A/B and D were classified as 2.MED3m. In addition, strains from rodents living near the patients’ residences were clustered into the same lineage as patients. Such observations indicated that human plague cases originated from local reservoirs. Corresponding phylogenetic analysis also indicated that rodent plague strains in different areas in Inner Mongolia belong to different epizootics rather than being caused by spreading from the same epizootic in Meriones unguiculatus in 2019.