bluuebunny/crossref_metadata_2025_split huggingface dataset:
Collectively Answering the Venetoclax BTK Inhibitor Sequencing Question in CLL
Authors: Rogers Kerry A. 
Published: May 2020

Abstract
Whether BTK inhibitors are effective when used after venetoclax in patients with chronic lymphocytic leukemia is an important unanswered question. In a large retrospective cohort study examining outcomes for next line treatment after venetoclax, BTK inhibitors were found to result in durable responses in patients who were not previously BTK inhibitor resistant.
See related article by Mato et al., p. 3589
<p><strong><em>Kalanchoe</em></strong><strong> ×<em>estrelae</em> (Crassulaceae subfam. Kalanchooideae): a new nothospecies for the hybrid between <em>K. luciae</em> and <em>K. sexangularis</em></strong></p>
Authors: SMITH GIDEON F. 
Published: May 2020

The cultivar name Kalanchoe Adanson (1763: 248) ‘Vivien’ Bischofberger (2015: 42) was established for a selection of the hybrid between K. luciae Raymond-Hamet (Hamet 1908: 256) (Fig. 1A) (see Smith 2020a for an explanation of the variable orthography of the name of Raymond-Hamet) and K. sexangularis Brown (1913: 120) (Fig. 1B) (Crassulaceae subfam. Kalanchooideae). The hybrid between these two species is variable and other forms of it, apart from K. ‘Vivien’, are also encountered in cultivation (Smith 2020b). Kalanchoe luciae and K. sexangularis are undoubtedly two of the most popular kalanchoes in domestic and amenity horticulture in South Africa, where they are indigenous (Smith et al. 2019b: 120). Geographically, both species extend northward into Zimbabwe and Mozambique in south-tropical Africa (Smith et al. 2019b: 189, 227).
How can today’s substance-using youth be helped to quit? Perspectives of college students from Bangalore, India
Authors: Doraiswamy Padmavathy , Nattala Prasanthi , Murthy Pratima 
Published: May 2020

Background: Substance use among college students is increasing, yet research regarding their viewpoints on how they can be helped is sparse in India. Aim: The purpose of this study was to explore in depth the perspectives of college students as to how college youth can be helped to quit the use of psychoactive substances. Method: Data from focus group interviews with 38 adolescent college students were analyzed qualitatively to identify their viewpoints on how today’s college youth can be helped to quit substance use. Interviews were transcribed verbatim, themes and subthemes were identified. Results: Three major themes (with subthemes) were identified: (1) Patterns of use (commonly used substances, methods of using), (2) Perceived reasons for use (to reduce negative emotions, academic pressure, peer influence, more freedom, rebellious attitudes, media influence, modeling effect, childhood trauma, distrust from family/friends, lack of knowledge regarding the adverse impact of substances, poor life skills, cultural gender-based discrimination) and (3) Interventions needed to help college youth to quit substance use (need for interventions, basic principles to follow when developing interventions, content to be included, methods to be employed for delivering the intervention). Conclusion: The information from this study can guide the development of a comprehensive intervention that is relevant and tailor-made to the specific needs of the college student population.
Response of a comprehensive cancer center to the COVID-19 pandemic: the experience of the Fondazione IRCCS–Istituto Nazionale dei Tumori di Milano
Authors: Valenza Franco , Papagni Gabriele , Marchianò Alfonso , Daidone Maria Grazia , De’Braud Filippo , Colombo Mario Paolo , Frignani Andrea , Galmozzi Gustavo , Ladisa Vito , Pruneri Giancarlo , Salvioni Roberto , Spada Pierangelo , Torresani Michele , Rinaldi Oliviero , Manfredi Stefano , Votta Marco , Apolone Giovanni 
Published: May 2020

Background: The rapid spread of coronavirus disease (COVID-19) is affecting many countries. While healthcare systems need to cope with the need to treat a large number of people with different degrees of respiratory failure, actions to preserve aliquots of the healthcare system to guarantee treatment to patients are mandatory. Methods: In order to protect the Fondazione IRCCS–Istituto Nazionale dei Tumori di Milano from the spread of COVID-19, a number of to-hospital and within-hospital filters were applied. Among others, a triage process to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity in patients with cancer was developed consisting of high-resolution low-dose computed tomography (CT) scan followed by reverse transcription polymerase chain reaction (RT-PCR) detection of SARS-CoV-2 in nose–throat swabs whenever CT was suggestive of lung infection. To serve symptomatic patients who were already admitted to the hospital or in need of hospitalization while waiting for RT-PCR laboratory confirmation of infection, a COVID-19 surveillance zone was set up. Results: A total of 301 patients were screened between March 6 and April 3, 2020. Of these, 47 were hospitalized, 53 needed a differential diagnosis to continue with their cancer treatment, and 201 were about to undergo surgery. RT-PCR was positive in 13 of 40 hospitalized patients (32%), 14 of 52 day hospital patients (27%), and 6 of 201 surgical patients (3%). Conclusion: Applying filters to protect our comprehensive cancer center from COVID-19 spread contributed to guaranteeing cancer care during the COVID-19 crisis in Milan. A surveillance area and surgical triage allowed us to protect the hospital from as many as 33 patients infected with SARS-CoV-2.
Immunophenotype-Genotype Correlations in Clear Cell Sarcoma of Kidney—An Evaluation of Diagnostic Ancillary Studies
Authors: Kenny Colin , Grehan David , Ulas Mevlut , Banga Gloria Badi , Coulomb Aurore , Vokuhl Christian , O'Sullivan Maureen J 
Published: May 2020

Introduction The purpose of this study was to establish a reliable panel of antibodies for immunohistochemical corroboration of a diagnosis of clear cell sarcoma of kidney (CCSK), taking into consideration the various genotypic subsets of CCSK. Methods We conducted full genotypic analysis for evidence of YWHAE-NUTM2, BCOR internal tandem duplication (ITD), and BCOR-CCNB3 in 68 archival cases of CCSK and then immunostained all cases for CCND1, TLE1, and BCOR along with 63 control samples representing tumor types that may enter into the differential diagnosis of CCSK, including 7 congenital mesoblastic nephromas, 2 desmoplastic small round cell tumors, 13 malignant rhabdoid tumors, 9 Ewing sarcomas/primitive neuroectodermal tumor, 5 synovial sarcomas, and 27 Wilms' tumors. Results Molecular assays showed that 54 CCSKs harbored a BCOR-ITD, 1 case expressed a YWHAE-NUTM2 fusion transcript while none expressed the BCOR-CCNB3 fusion. The remaining 13 CCSKs were designated “triple-negative” based on the molecular findings. CCND1 showed positive immunoreactivity across all subgroups. TLE1 was positive in 94% of cases, including 1 YWHAE-NUTM2 fusion-positive case. Three BCOR-ITD-positive tumors were TLE1-negative. BCOR immunostaining was most variable among subgroups, with triple-negative tumors showing the weakest staining. In all, 10/68 (15%) tumors did not stain for BCOR, of which 4 were triple-negative (4/13 = 31%) and 6 were BCOR-ITD-positive (6/54 = 11%). The single YWHAE-NUTM2-positive tumor showed strong staining for all 3 markers. No single case was negative for all 3 stains; however, 3 cases showed no reactivity for either BCOR or TLE1 of which 1 was triple-negative and 2 BCOR-ITD-positive. Conclusion Having completed the first comprehensive evaluation of immunostaining of 68 fully genotyped CCSK tumors, we show herein that there is a rationale for the use of a small panel of antibodies to assist in the diagnosis of CCSK regardless of genotype, and we demonstrate that in combination CCND1, TLE1, and BCOR are compelling markers in aiding CCSK diagnosis.
Do trabecular metal cups achieve better results when compared to hemispherical porous titanium cups in acetabular revision surgery?
Authors: Cruz-Pardos Ana , García-Rey Eduardo , Fernandez-Fernández Ricardo , Ortega-Chamarro José 
Published: May 2020

Background: Trabecular metal (TM) cups were introduced in order to achieve better ingrowth and stability of the cup in acetabular revision surgery. As their use has evolved over time, we have queried whether TM cups would improve results in terms of the rate of aseptic loosening when compared to historical uncemented porous titanium cups used in revision surgery for acetabular bone loss in Hospital La Paz (Madrid, Spain). Methods: We retrospectively reviewed 197 acetabular revisions performed between 1991 and 2015. Titanium cups were used in 81 cases and TM cups in 116. The mean follow-up was 8.1 years (range 1–15); 12.0 ± 7.8 for titanium group and 5.4 ± 3.1 for TM group. The most common reason for revision was aseptic loosening. A Kaplan-Meier analysis was used to determine the survival of the cup, with radiological failure and re-revision due to aseptic loosening as the endpoints. Cox multivariate regression analyses were performed to assess different risk factors for failure. Results: 1 TM cup and 1 titanium cup were re-revised due to aseptic loosening ( p = 0.61). Radiological cup loosening was observed in 4 TM cups and 2 titanium cups ( p = 1.0). At 6 years, the probability of not having radiological cup loosening was 97.4% (95% CI, 93.9–100) for the titanium cups and 95.1% for the TM cups (95% CI, 90.1–99.9) ( p = 0.59). Another 5 cups were re-revised due to dislocation. Hips with a greater Paprosky defect showed a higher risk of loosening ( p < 0.05, hazard risk (HR) 3.04; 95% CI, 0.97–9.54). Conclusions: This study shows there was no significant difference in re-revision due to aseptic loosening or radiological loosening between titanium and TM cups in revision surgery for acetabular bone loss. Both types of cups demonstrate excellent results with a low failure rate and minimal complications.
Mutations in MC4R facilitate the angiogenic activity in patients with orbital venous malformation
Authors: Huang Xiao-Ming , Yang Wan-Chen , Liu Yang , Tang Dong-Run , Wu Tong , Sun Feng-Yuan 
Published: May 2020

Orbital venous malformation results from the aberrant angiogenesis in the orbit; however, the detailed molecular mechanism is still not clear. In this study, tissue samples from 27 patients with orbital venous malformation were collected and subjected to whole exome sequencing. Melanocortin 4 receptor was the gene with highest incidence (7/27) of mutation identified in this series. A total of four types of mutations were found in the coding region and the 5ʹ-untranslated region of melanocortin 4 receptor. All these mutations resulted in the upregulation of melanocortin 4 receptor expression. In vitro assays using human umbilical vein endothelial cells demonstrated that the endothelial properties including cell proliferation, cell cycle, cell migration, and tube formation are positively correlated with the expression level of melanocortin 4 receptor. Melanocortin 4 receptor mutations resulted in increased cAMP production in a cell-based assay. By RNA sequencing technique, melanocortin 4 receptor was found to modulate the downstream genes of PI3K/AKT/mTOR pathway, including p21, cyclin B1, ITGA10, and ITGA11, which are known to regulate the endothelial properties. These data demonstrated that mutations in melanocortin 4 receptor modulate the downstream signaling pathway, facilitate the angiogenic activity of endothelial cells, and therefore is one potential mechanism of orbital venous malformation pathogenesis.Impact statementThe detailed molecular mechanism of orbital venous malformation (OVM) is still not clear. Using whole exome sequencing, 4 types of melanocortin 4 receptor (MC4R) mutation were detected in 7 of 27 patients with OVM, and all types of MC4R mutations resulted in the upregulation of MC4R expression. In vitro study indicated that MC4R has impacts on the proliferation, cell cycle, migration, and tube formation of the endothelial cells. Moreover, MC4R mutations altered the downstream signaling, including cAMP concentration and the expression levels of several PI3K/AKT/mTOR downstream genes, including p21, cyclin B1, ITGA10, and ITGA11. MC4R mutations may lead to the pathogenesis of OVM through modulating the downstream signaling to alter the angiogenic activity of endothelial cells.
Examination of fluoroscopy monitor as a source of indirect bacterial contamination in orthopaedic surgery
Authors: Radley Joseph M , Gloekler Daniel S , Krahe Mark A , Nechleba Jeffrey A 
Published: May 2020

Background: Surgical site infection is a well-documented complication of surgery. While contact with fomites represents a recognised source of contamination, electrostatic charge can cause contamination without surface contact as shown in previous studies evaluating operating room equipment. In cases requiring fluoroscopy, an intraoperative X-ray method, it is common for a surgeon to point to the associated monitor, particularly when teaching. This close proximity without direct contact poses a theoretical risk of contamination due to potential electrostatic forces. Aim/Objective: To assess whether a gloved finger could be contaminated by a fluoroscopy monitor without direct contact. Methods: Using a laser-guided level, a sterile, gloved finger was traversed side-to-side, top-to-bottom, across a fluoroscopy monitor used during surgery at distances of 1 cm, 2 cm, 4 cm and 8 cm. Two negative controls and a positive control were collected for comparison. Specimens were inoculated onto agar plates and incubated for 48 h at 37 °C. Following incubation, samples were analysed for growth and the number of colonies was recorded. This was repeated during 10 randomly selected operative cases using fluoroscopy for a total of 70 samples. Results: No bacterial growth was identified as a result of inoculation on any of the 70 experimental or control specimens. Discussion: We conclude that the practice of pointing to a fluoroscopy monitor for educational or other purposes is unlikely to increase the risk of glove contamination.
Benefits of the Subdural Evacuating Port System (SEPS) Procedure Over Traditional Craniotomy for Subdural Hematoma Evacuation
Authors: Golub Danielle , Ashayeri Kimberly , Dogra Siddhant , Lewis Ariane , Pacione Donato 
Published: May 2020

Background: There remains no consensus on the optimal primary intervention for subdural hematoma (SDH). Although historically favored, craniotomy carries substantial morbidity and incurs significant costs. Contrastingly, the subdural evacuating port system (SEPS) is a minimally invasive bedside procedure. We assessed the benefits of SEPS over traditional craniotomy for SDH evacuation. Methods: A single-center retrospective cohort study of SDH patients receiving craniotomy or SEPS between 2012 and 2017 was performed. Information regarding demographics, medical history, presentation, surgical outcomes, cost, and complications was collected. Pre- and postoperative hematoma volumes were calculated using 3D image segmentation using Vitrea software. Multivariate regression models were employed to assess the influence of intervention choice. Results: Of 107 patients, 68 underwent craniotomy and 39 underwent SEPS. There were no differences in age, sex, blood thinner use, platelet count, INR, hematoma lateralization, age, volume, or midline shift at presentation between intervention groups. Although there was no difference in percent residual hematoma volume 24-hour postintervention (44.1% vs 45.1%, P = .894), SEPS was associated with lower hospitalization costs ($108 391 vs $166 318, * P = .002), shorter length of stay (4.0 vs 5.8 days, * P = .0002), and fewer postoperative seizures (2.6% vs 17.7%, * P = .048). Reoperation rate was higher after SEPS overall (33.3% vs 13.2%, * P = .048) but comparable to craniotomy in chronic SDH (12.50% vs 7.69%, P = 1.000). Conclusion: In this retrospective cohort, SEPS was noninferior to craniotomy at reducing SDH hematoma volume. The SEPS procedure was also associated with decreased length of stay hospitalization costs, and postoperative seizures and demonstrated a comparable recurrence rate to craniotomy for chronic SDH in particular.
TS: a powerful truncated test to detect novel disease associated genes using publicly available gWAS summary data
Authors: Zhang Jianjun , Guo Xuan , Gonzales Samantha , Yang Jingjing , Wang Xuexia 
Published: May 2020

AbstractBackgroundIn the last decade, a large number of common variants underlying complex diseases have been identified through genome-wide association studies (GWASs). Summary data of the GWASs are freely and publicly available. The summary data is usually obtained through single marker analysis. Gene-based analysis offers a useful alternative and complement to single marker analysis. Results from gene level association tests can be more readily integrated with downstream functional and pathogenic investigations. Most existing gene-based methods fall into two categories: burden tests and quadratic tests. Burden tests are usually powerful when the directions of effects of causal variants are the same. However, they may suffer loss of statistical power when different directions of effects exist at the causal variants. The power of quadratic tests is not affected by the directions of effects but could be less powerful due to issues such as the large number of degree of freedoms. These drawbacks of existing gene based methods motivated us to develop a new powerful method to identify disease associated genes using existing GWAS summary data.Methods and ResultsIn this paper, we propose a new truncated statistic method (TS) by utilizing a truncated method to find the genes that have a true contribution to the genetic association. Extensive simulation studies demonstrate that our proposed test outperforms other comparable tests. We applied TS and other comparable methods to the schizophrenia GWAS data and type 2 diabetes (T2D) GWAS meta-analysis summary data. TS identified more disease associated genes than comparable methods. Many of the significant genes identified by TS may have important mechanisms relevant to the associated traits. TS is implemented in C program TS, which is freely and publicly available online.ConclusionsThe proposed truncated statistic outperforms existing methods. It can be employed to detect novel traits associated genes using GWAS summary data.
Comparative analysis of similarity measurements in miRNAs with applications to miRNA-disease association predictions
Authors: Chen Hailin , Guo Ruiyu , Li Guanghui , Zhang Wei , Zhang Zuping 
Published: May 2020

AbstractBackgroundAs regulators of gene expression, microRNAs (miRNAs) are increasingly recognized as critical biomarkers of human diseases. Till now, a series of computational methods have been proposed to predict new miRNA-disease associations based on similarity measurements. Different categories of features in miRNAs are applied in these methods for miRNA-miRNA similarity calculation. Benchmarking tests on these miRNA similarity measures are warranted to assess their effectiveness and robustness.ResultsIn this study, 5 categories of features, i.e. miRNA sequences, miRNA expression profiles in cell-lines, miRNA expression profiles in tissues, gene ontology (GO) annotations of miRNA target genes and Medical Subject Heading (MeSH) terms of miRNA-associated diseases, are collected and similarity values between miRNAs are quantified based on these feature spaces, respectively. We systematically compare the 5 similarities from multi-statistical views.Furthermore, we adopt a rule-based inference method to test their performance on miRNA-disease association predictions with the similarity measurements. Comprehensive comparison is made based on leave-one-out cross-validations and a case study. Experimental results demonstrate that the similarity measurement using MeSH terms performs best among the 5 measurements. It should be noted that the other 4 measurements can also achieve reliable prediction performance. The best-performed similarity measurement is used for new miRNA-disease association predictions and the inferred results are released for further biomedical screening.ConclusionsOur study suggests that all the 5 features, even though some are restricted by data availability, are useful information for inferring novel miRNA-disease associations. However, biased prediction results might be produced in GO- and MeSH-based similarity measurements due to incomplete feature spaces. Similarity fusion may help produce more reliable prediction results. We expect that future studies will provide more detailed information into the 5 feature spaces and widen our understanding about disease pathogenesis.
Intravenous dexmedetomidine versus tramadol for treatment of shivering after spinal anesthesia: a meta-analysis of randomized controlled trials
Authors: Wang Jinguo , Wang Zaitang , Liu Junyan , Wang Na 
Published: May 2020

AbstractBackgroundShivering is a frequent complication after spinal anesthesia. Increasing studies have compared the effect of intravenous dexmedetomidine and intravenous tramadol on shivering after spinal anesthesia, hence we performed a meta-analysis of randomized controlled trials to compare dexmedetomidine with tramadol on the treatment of post-spinal anesthesia shivering.MethodsPubMed, Embase, Cochrane library, Web of Science and Google Scholar were searched to find the eligible studies comparing the effect of dexmedetomidine and tramadol on the treatment of shivering after spinal anesthesia. Mean difference (MD) or risk ratio (RR) along with 95% confidence interval (CI) was used to analyze the outcomes. I2test was conducted to assess the heterogeneity of the included trials. We utilized Review Manager 5.3 to perform statistical analyses.ResultsThirteen randomized controlled trials including 864 subjects were included. Dexmedetomidine had higher effective rate of shivering control (RR =1.03; 95%CI [1.01, 1.06],P = 0.01, I2 = 14%), shorter time to cease shivering (MD = -2.14; 95%CI [− 2.79, − 1.49],P < 0.00001, I2 = 98%), lower recurrent rate of shivering (RR = 0.45; 95%CI [0.27, 0.73],P = 0.001, I2 = 0%), lower incidences of nausea (RR = 0.10; 95%CI [0.05, 0.19], P < 0.00001, I2 = 48%), and vomiting (RR = 0.13; 95%CI [0.06, 0.30], P < 0.00001, I2 = 0%), higher incidence of sedation (RR = 2.48; 95%CI [1.32, 4.65],P = 0.005, I2 = 82%), hypotension (RR = 2.50; 95%CI [1.24, 5.03],P = 0.01, I2 = 0%) and bradycardia (RR = 4.78; 95%CI [1.76, 13.00],P = 0.002, I2 = 0%), compared with tramadol.ConclusionsDexmedetomidine is superior to tramadol for shivering treatment, due to higher effective rate of shivering control, earlier onset of action and lesser recurrence of shivering with higher incidence of sedation and lower incidences of nausea and vomiting. However, dexmedetomidine is also associated with higher incidences of hypotension and bradycardia than tramadol.