bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of enfortumab vedotin in advanced urothelial cancer: Retrospective analysis of the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) Study.
Authors: Koshkin Vadim S , Sun Yilun , Freeman Dory , Osterman Chelsea K. , Su Christopher , Natesan Divya , Khaki Ali Raza , Makrakis Dimitrios , Jain Jayanshu , Olsen Anders , Basu Arnab , Barata Pedro C. , Zakharia Yousef , Bilen Mehmet Asim , Emamekhoo Hamid , Davis Nancy B. , Milowsky Matthew I. , Kilari Deepak , Sonpavde Guru , Alva Ajjai Shivaram
Published: March 2021

443

Background: Enfortumab vedotin (EV) is an antibody-drug conjugate targeting Nectin-4, which is FDA approved for patients (pts) with treatment-refractory advanced urothelial cancer (aUC). The activity of EV in pt subsets of interest such as those with distinct histological variants has not been well defined. Methods: A retrospective study of pts with aUC treated with ≥1 dose of EV as standard of care (SOC) or on a clinical trial (if trial results already reported) at 12 US sites was undertaken. Objective response rate (ORR) was investigator-assessed for pts with at least one post-baseline scan or clear evidence of clinical progression. ORR was compared across subsets of interest using proportion test. Results: A total of 184 patients with aUC were included; median age at diagnosis 70, 20% women and 60% with definitive surgery. Most common primary sites included bladder (70%) and upper tract (28%). Majority of pts (72%) had pure urothelial histology (UH) per local review, but 26% had at least a component of variant histology (VH), most commonly squamous (14%), micropapillary (8%) or plasmacytoid (3%). EV was given as monotherapy in 84% and as SOC in 58%; and 81% had ≥ 1 prior treatment in the metastatic (met) setting. ECOG PS was ≥2 in 15%; 37% had baseline neuropathy, 15% diabetes and 9% had GFR≤30. At median follow-up of 37.0 (IQR: 20.5-60.2) months from initial diagnosis, median time from met diagnosis to EV start was 11.7 (IQR: 4.3 – 20.5) months. Median duration of EV was 5.5 (IQR: 1.4 – 6.7) months, and 84% of pts were evaluable for response. ORR for evaluable pts was 53% (8% CR, 45% PR); 25% had SD and 21% PD. Median PFS and OS were not yet reached. At data cutoff in 9/2020, 55% had stopped EV (36% due to PD, 19% intolerance) and 65% were alive. Comparison of ORR in subgroups of interest for 127 evaluable pts treated with EV monotherapy is shown in the table below. Notably, among 31 pts with FGFR3 alterations, 26 were evaluable and ORR was 46%. Conclusions: In a large, retrospective, multi-institutional cohort, responses to EV were observed across a broad range of aUC pts, including pts with variant histology component, FGFR3 alterations and also in populations previously excluded from clinical trials such as pts with GFR<30 and significant baseline comorbidities. No significant differences in ORR were demonstrated for patient subsets of interest. [Table: see text]
Genomic landscape of variant urinary tumor histologies.
Authors: Abou Alaiwi Sarah , Nassar Amin , Adib Elio , Akl Elie W. , Mouw Kent William , Curran Catherine , Freeman Dory , Ravi Praful , Mantia Charlene , Acosta Andres , Preston Mark A. , Mossanen Matthew , Kwiatkowski David J. , Sonpavde Guru
Published: March 2021

467

Background: The genetics of urothelial carcinoma (UC), the most common histology of urinary tract (UT) tumors, is well characterized; much less is known about the genomic features of rare histologic variants of UT tumors. We aim to compare the genomic alterations (GA) of UT tumors with adenocarcinoma (AD), small cell (SC), squamous cell (SQ), or plasmacytoid (PC) histologies, to UC tumors. Methods: We identified patients with pure variant (AD, SC, SQ, PC) or UC histology with genetic characterization through the GENIE registry. Patient tumor genomic data were captured by Memorial Sloan Kettering Cancer Center (MSK)-IMPACT and Dana-Farber Cancer Institute (DFCI)-Oncopanel NGS initiatives. Tumors with mixed histology were excluded. We limited our analysis to genes tested >1000 times (N=211). Mutation frequencies and copy number variants (CNVs), collectively called GAs, were determined for AD, SC, SQ, PC, and UC, and were compared using the Fisher’s Exact test and Kruskall Wallis test. Nominal p values were obtained, and FDR correction was employed (q < 0.1). Results: We identified 1199 patients with available genomic data who met the inclusion criteria. Histologic distribution was: 32 AD, 13 SC, 15 SQ, 11 PC, and 1128 UC tumors. The median age was 68 years and 77% of patients were male. Statistically significant differences in genetic alterations by subtype are shown in the table below. ARID1A and KDM6A GAs were higher in UC; PC and SC; CDH1 GAs higher in PC; RB1 and TP53 GAs higher in SC; SMAD4 GAs higher in AD; and NFE2L2 GAs higher in SQ. Conclusions: Variant UT histologies exhibit a distinct pattern of alterations compared to UC, consistent with their divergent clinical behavior. This suggests different biological origins for these variant histologies and possibly different therapeutic vulnerabilities. Exploring the GAs of these UT tumors in larger datasets is warranted. [Table: see text]
Hyperthermia, bladder pressure, and intravesical drug delivery.
Authors: Grimberg Dominic C. , Campbell Scott P. , Etienne Wiguins , Fan Ping , Maccarini Paolo F. , Spasojevic Ivan , Arcot Rohith , Shah Ankeet , Inman Brant Allen
Published: March 2021

469

Background: Little is known about the pharmacokinetics of intravesical chemotherapies. Various parameters can be altered including temperature, dwell time, drug concentration, and bladder pressure. Here, we hypothesize that increasing bladder pressure during instillation will improve drug delivery. Methods: An ex-vivo porcine model was developed to evaluate determinants of drug penetration into the bladder wall. Porcine bladders were suspended in isotonic saline at 37°C with a three-way Foley catheter in the bladder. Temperature probes were positioned in the extravesical bathing solution, bladder lumen, and sutured to the detrusor to ensure maintenance of desired temperatures. 2g gemcitabine in 100mL normal saline was heated to 43°C and circulated through the bladder using the Combat Bladder Recirculation System. Bladder pressures were monitored throughout each trial. After 60 minutes of dwell time, rapid dissection was performed to obtain full-thickness bladder samples from the bladder dome, posterior wall, trigone, and left and right lateral walls. Tissue was homogenized and liquid chromatography with tandem mass spectrometry (LC/MS/MS) was performed to measure gemcitabine concentration within the bladder wall. Linear regression and Pearson correlation were performed to determine the association between mean bladder pressure during instillation and drug concentration within the bladder wall. Multiple linear regression was conducted to control for bladder location and thickness. Results: Gemcitabine concentration within the bladder wall was measured 25 times across five trials. Mean gemcitabine concentration within bladder wall was 3.68 mg/g (sd 1.35). Pressure ranged from 149.8 mmHg to 277.7 mmHg (mean 194.8, sd 22.0). On univariate analysis, higher pressure was associated with increased gemcitabine concentration within the bladder wall (correlation = 0.49, p = 0.013). This result persisted after adjusting for bladder location (ß = 0.49, p = 0.006) and thickness (ß = 0.70, p = 0.03). Unstandardized regression coefficient in each of the models was 0.099 (mmHg x g)/mg, demonstrating that for each pressure increase of 10mmHg there was an associated increase in gemcitabine concentration of approximately 1 mg/g (Table). Conclusions: Data suggest that bladder pressure dramatically improves the extent of gemcitabine penetration into the bladder wall. Future research is needed to evaluate the therapeutic effect of increased gemcitabine delivery to target tissue in patients with bladder cancer. [Table: see text]
Real-world clinical outcomes study of sequential novel antihormonal therapy (NAH) or radium-223 (Ra-223) treatment of metastatic castration-resistant prostate cancer (mCRPC) that progressed after first-line NAH.
Authors: Sartor Oliver A. , George Daniel J. , Tombal Bertrand , Higano Celestia S. , Sternberg Cora N. , Miller Kurt , Jiao Xiaolong , Guo Helen , Sandstrom Per , Verholen Frank , Saad Fred , Shore Neal D.
Published: March 2021

48

Background: We assessed real-life clinical outcomes in patients with mCRPC treated in the USA who received sequential first-line (1L)/second-line (2L) NAH (abiraterone/enzalutamide or enzalutamide/abiraterone) or switched to a different mechanism of action (alpha-emitter Ra-223) after progression on 1L NAH. Methods: This was a retrospective study (PHENIX, NCT03896984) of the Flatiron electronic health record database in patients with mCRPC that progressed on 1L NAH and started 2L monotherapy with Ra-223 (n=120) or NAH (n=226) between Jan 2013 and Dec 2018. Patient characteristics, overall survival (OS) from 2L start, and symptomatic skeletal events (SSEs) were analyzed descriptively. Results: The two cohorts were generally similar at 2L start, including similar rates of bone-health agent (BHA) use, but the Ra-223 cohort had a higher incidence of bone-only metastases, shorter duration of 1L NAH, and higher rate of prior SSEs than the 2L NAH cohort (Table). Median treatment duration was 5.6 mo (median 4.5 doses) for Ra-223 and 4.7 mo for 2L NAH. Median OS from 2L start was 10.8 mo for Ra-223 and 11.2 mo for 2L NAH, with 49% and 39%, respectively, receiving subsequent therapy. Among those who received subsequent therapy, the proportion who received subsequent taxane was lower in the Ra-223 cohort (47%) than in the 2L NAH cohort (76%). SSEs were observed after 2L start in 32 patients (27%) on Ra-223 and 49 (22%) on 2L NAH. Conclusions: OS from start of 2L mCRPC treatment was similar for patients who received Ra-223 or alternative NAH in 2L. Slightly more patients received subsequent therapy in the Ra-223 cohort than in the 2L NAH cohort. Patients who received subsequent therapy were more likely to receive chemotherapy in the 2L NAH cohort, which is unsurprising as 2L NAH after 1L NAH is not highly active. Although the prior SSE rate before 2L start was higher in the Ra-223 cohort than in the 2L NAH cohort, and the two cohorts had similar rates of BHA use at 2L start, the rate of SSEs after 2L start was similar in both cohorts. Clinical trial information: NCT03896984. [Table: see text]
Multi-omics prognosis predictive model of metastatic urothelial carcinoma (mUCs) with immunotherapy.
Authors: He Ning , Zhang Yiqun , Yang Yadong , Wang Jianfei
Published: March 2021

482

Background: A fraction of mUCs patients can occur robust and durable responses in metastatic urothelial cancer patients treated with anti-PD-L1 agent (atezolizumab), and prognosis of immunotherapy exhibited a lack of attention. We aim to develop an effective prognosis for mUCs patients’ immunotherapy management. Methods: Public omics and clinical data of patients were collected from R package “IMvigor210CoreBiologies” (348 samples with RNA sequencing data, and 293 samples with DNA sequencing data). Immune cell infiltrations in the tumor microenvironment were quantified by single sample Gene Set Enrichment Analysis (ssGSEA). Prognosis model were trained by elastic net Cox proportional hazards algorithm, 10-fold Cross Validation were used for avoiding over fitting. Statistical analysis, survival analysis and data visualization were all carried out using the R. Results:Based on the whole transcriptome, whole exome sequencing, data were processed into five class parameters (including immunohistochemical, gene mutation, gene expression, signature score and molecular subtyping). With regularized Cox regression analysis, 17 genes ( CXCL9, GJB2, THBD, SEPT3, PLTP, LDLR, PPM1H, ACVR1C, MT1G, MT1L, ANXA2, LOC102725117, PCDHGB7, MCF2L2, APOL6, ITGAV, PCDH11X) were selected for evaluating mRNA expression level risk score, 11 immune cells (TIS, TGFβ, Activated CD8+ T cell, Central memory CD4+ T cell, Central memory CD8+ T cell, Effector memory CD4+ T cell, Gamma delta T cell, Memory B cell, Eosinophil, Immature dendritic cell, Monocyte neutrophil) were selected for evaluating pathway level risk score. Then we combined mRNA risk score, signature risk score, gene mutations, PD-L1 IHC, TMB and other clinical parameters for further dimension reduction. Finally, PD-L1 in tumor-infiltrating immune cells (ICs) (HR = 0.75, 95% CI 0.64-0.89, p < 1e-03), mRNA risk score (HR = 3.06, 95% CI 2.42-3.86, p < 1e-06) and TMB (HR = 0.75, 95% CI 0.64-0.89, p < 1e-03) were selected for Cox-model. Samples were divided into groups were by median of risk score, and there were significant difference of overall survival between high-risk and low-risk group, in training dataset (p < 1e-04, AUC( t = 6m/12m/18m) = 0.69/0.79/0.80) and validation dataset (p < 1e-04, AUC( t = 6m/12m/18m) = 0.77/0.82/0.85). In addition, high risk group was less response to PD-L1 immunotherapy than low risk group in our research (χ2 test, p < 2.23e-06). Conclusions: Wefirstlyconstructed a multi-omics prognosis prediction model for mUCs with immunotherapy, which may be related to different prognosis and immunotherapy response. This result may help further understanding the anti-immunotherapy of mUCs patient’s management.
Evaluating financial burdens of oral hormonal therapies for patients with prostate cancer.
Authors: Schwartz Eric B , Jeong Angelina , Roman Andrea , McDevitt Rachel , Henry Elyssa , Caram Megan Veresh
Published: March 2021

70

Background: Numerous oral anticancer drugs approved for metastatic prostate cancer are expensive and put patients at risk for financial toxicity. Mechanisms available to mitigate these costs are complex to navigate. Furthermore, the ability to access these resources may not be the same for every insurance. We examined the out-of-pocket (OOP) liability of patients prescribed abiraterone or enzalutamide, the assistance mechanisms used, and the impact on timing of therapy. Methods: Patients with prostate cancer who were prescribed abiraterone or enzalutamide at our comprehensive cancer center between January 1, 2017 and March 31, 2019 were identified. Patients who filled prescriptions via an external pharmacy were excluded. Data regarding demographics, out of pocket costs and assistance mechanisms were evaluated. Results: We identified 219 patients. Of these, 33% had commercial insurance, 61% had Medicare part D, 3% had Medicaid and 8% had no insurance. Most patients (74%) were prescribed abiraterone and 26% enzalutamide. Among those with Medicare Part D, almost one third received significant financial assistance: 11% free drug from the manufacturer and 18% foundational grants. Patients with commercial insurance received a copay card from manufacturers 21% of the time. Patients with commercial insurance paid an average of $57 OOP; 94% with initial cost < $100. Patients with Medicare part D paid an average of $582 OOP; 22% with initial cost > $1000. Commercially insured patients started treatments in under 10 days from the prescription date 51% of the time vs 39% for Medicare patients. In contrast, 11% of commercially insured patients required > 30 days to fill vs 19% on Medicare. Only 1% of commercially insured patients were unable to fill due to cost issues compared to 7% of patients on Medicare. Conclusions: Financial assistance mechanisms such as grants and free drug programs help alleviate some financial burden for patients, but many still experience high OOP costs. These burdens appear to be disproportionately experienced by patients with Medicare Part D. We observed that patients with Medicare Part D had higher OOP costs for oral prostate cancer therapies. Those who required assistance often experienced delays in obtaining medication. Further evaluation is planned into how high costs and delays in treatment impacts prostate cancer treatment and patient care. [Table: see text]
PROSPER subgroup analysis by age and region: Overall survival and safety in men with nonmetastatic castration-resistant prostate cancer receiving androgen deprivation therapy plus enzalutamide.
Authors: De Giorgi Ugo , Hussain Maha H. A. , Shore Neal D. , Fizazi Karim , Tombal Bertrand , Penson David F. , Saad Fred , Efstathiou Eleni , Madziarska Katarzyna , Steinberg Joyce Leta , Sugg Jennifer , Lin Xun , Shen Qi , Sternberg Cora N.
Published: March 2021

84

Background: Previous reports on the PROSPER trial have shown that enzalutamide (ENZA) plus androgen deprivation therapy (ADT) significantly improves metastasis-free survival and overall survival (OS) over placebo (PBO) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC) and rapidly rising prostate-specific antigen (PSA) levels. (Hussain et al. N Engl J Med. 2018;378:2465-2474/Sternberg et al. N Engl J Med. 2020;382:2197-2206). To inform decision-making for specific patients, we report here a post hoc analysis of OS and safety in subgroups of PROSPER by age and region. Methods: PROSPER included men with nmCRPC and a PSA doubling time ≤ 10 months. Enrolled men continued ADT and were randomized 2:1 to ENZA 160 mg once daily vs PBO. We performed a multivariable analysis for OS, including age (≤ 70 yrs and > 70 yrs), geographic region, and other variables and further examined exposure-adjusted adverse events (AEs) by age and region. Results: Based on this post hoc analysis, OS benefit with ENZA treatment was similar across geographic regions (table) and for patients aged ≥ 70 yrs (hazard ratio [HR] 0.73; 95% CI 0.58-0.9) and those aged < 70 yrs (HR 0.72, 95% CI 0.5-1.04). In our multivariate analysis, 3 factors emerged as significantly impacting estimated OS: Eastern Cooperative Oncology Group (ECOG) performance status (1 vs 0; HR 1.7; 95% CI 1.4-2.1), log of PSA (HR 1.2; 95% CI 1.1-1.3), and use of subsequent therapy (yes vs no; HR 2.5; 95% CI 2.1-3.1). Overall safety was consistent between age groups and across geographic regions. The proportion of patients reporting any grade treatment-emergent AEs (TEAEs) related to ENZA use was similar between age groups but decreased with increasing age. Conclusions: In men with nmCRPC and rapidly rising PSA, ENZA plus ADT treatment reduced the risk of death, regardless of age or geographic location. Patients reported any grade TEAEs at a similar proportion in both arms. Variables impacting OS included ECOG status, log PSA, and subsequent therapy. Clinical trial information: NCT02003924. [Table: see text]
An open-label phase II study comparing two doses of MK-6482 for the treatment of advanced renal cell carcinoma (RCC) following progression on prior systemic therapy.
Authors: Atkins Michael B. , Liu Yanfang , Perini Rodolfo F. , Roy Ananya , Haanen John B. A. G.
Published: March 2021

TPS369

Background: Treatment options for RCC in the late-line setting after immunotherapy and vascular endothelial growth factor (VEGF)-targeted therapy are limited. Hypoxia-inducible factor (HIF)-2α is a transcription factor that has been established as an oncogenic driver in clear cell RCC (ccRCC). The first-in-class small molecular HIF-2α inhibitor, MK-6482, recently showed promising antitumor activity in a cohort of heavily pretreated ccRCC patients (pts) and in pts with von Hippel-Lindau–disease-associated RCC for which the FDA granted Breakthrough Therapy Designation to MK-6482. Methods: This randomized, open-label, multicenter phase II trial will evaluate the efficacy and safety of 2 doses of MK-6482 in pts with advanced RCC who have experienced progression after prior systemic therapy (NCT04489771). Eligible pts are male or female aged ≥18 years with histologically confirmed locally advanced or metastatic ccRCC (measurable disease per RECIST v1.1) who have experienced progression after 1-3 prior systemic therapies comprising an anti-PD-1/L1 agent combined with a VEGF-targeted tyrosine kinase inhibitor (TKI) or an anti-cytotoxic T lymphocyte-associated antigen-4 agent and have undergone no more than 3 prior systemic regimens; and a Karnofsky Performance Scale ≥70. Treatment progression on anti-PD-1/L1 combination therapy was defined as pts who received at least 2 doses of anti-PD-1/L1 therapy and demonstrated radiographic disease progression as assessed by the investigator. Pts who have received prior treatment with MK-6482 or another HIF-2α inhibitor, and those requiring intermittent or chronic supplemental oxygen, or with a baseline hemoglobin less than 10 g/dL, a history of human immunodeficiency virus, hepatitis B or hepatitis C infection, or active central nervous system metastases will be excluded. Approximately 150 pts will be randomly assigned 1:1 to oral MK-6482 120 mg once daily (QD) or 200 mg QD; treatment will continue until progression, unacceptable toxicity, or withdrawal. Pts will be stratified by International Metastatic RCC Database Consortium prognostic scores (0, 1-2, 3-6) and the number of prior TKI-containing therapies (0, 1, or 2-3). Imaging with computed tomography or magnetic resonance imaging will be undertaken on Week 9 from the date of randomization, every 8 weeks through Week 49, and every 12 weeks thereafter. Adverse events will be monitored throughout the study and for 30 days after treatment (90 days for serious adverse events). The primary end point is objective response rate per RECIST v1.1 by blinded independent central review (BICR). Secondary end points are progression-free survival, duration of response and clinical benefit rate per RECIST v1.1 by BICR, overall survival, pharmacokinetics, and safety. Safety will be analyzed using a tiered approach. This study is recruiting. Clinical trial information: NCT04489771 .
A Round Trip: The Japanese Contribution to the Development of Sevoflurane
Authors: Ikeda Shigemasa , Makino Hiroshi
Published: March 2021

Sevoflurane was first synthesized independently by Richard Wallin and Bernard Regan at Travenol Laboratories Incorporated and Ross Terrell and Louise Croix at Airco, Inc in the late 1960s, and subsequent animal studies and a phase-1 human trial of the agent published in 1981 showed promising results. Further research in the United States was halted, however, because of concerns regarding potential nephrotoxicity and the introduction of less degradable alternatives. Interest in sevoflurane resumed in Japan when Maruishi Pharmaceutical Company, Limited (Ltd) (Maruishi) decided to continue its development in 1982. They secured approval by the Japanese Ministry of Health, Labor and Welfare for its clinical use in January 1990. Because of its low blood:gas partition coefficient and resulting rapid action, sevoflurane quickly became the anesthetic of choice of Japanese anesthesiologists. In 1992 Abbott Laboratories, now AbbVie, Inc (Abbott, North Chicago, IL) finalized a licensing agreement with Maruishi to seek the US Food and Drug Administration approval for sevoflurane sales in the United States. Approved in June 1995, sevoflurane is now marketed by Abbott in 120 countries and has been administered >120 million times. This report details the Japanese contribution to the development of sevoflurane.
Family planning science and practice lessons from the 2018 International Conference on Family Planning
Authors: Rusatira Jean Christophe , Silberg Claire , Mickler Alexandria , Salmeron Carolina , Twahirwa Rwema Jean Olivier , Johnstone Maia , Martinez Michelle , Rimon Jose G. , Zimmerman Linnea
Published: March 2021

Background

Since 2009, the International Conference on Family Planning (ICFP) has served as an opportunity for the global reproductive health community to share FP advances and practice lessons in the areas of research, programming, and advocacy. The purpose of this paper was to synthesize the key results and findings presented by members of the FP community at the 2018 ICFP Conference.

Methods

More than 700 abstracts from all 15 conference tracks were reviewed and 64 abstracts total were selected for this paper based on the novelty and urgency of the findings. The content analysis of conference abstracts were grouped into six final thematic areas.

Results

1) Investing in family planning for a lifetime of returns. FP continues to face a shortage of funding. Domestically based and locally owned funding models provide alternative financing solutions. 2) Addressing inequities in family planning for key populations. Various populations still face challenges in accessing FP. Youth-inclusive and user-centered programming show promise in addressing such challenges. 3) Reproductive justice, Unsafe abortions tend to be more common among younger, poor, uneducated and rural women. Legislation is still needed to facilitate a culture of safe abortions. 4) Couple dynamics and decision-making. Couples who share equitable responsibility in decision-making processes are more likely to use contraceptives; couple disagreement influences women’s decisions to covertly use FP. 5) Male involvement in  programming. Male champions can successfully promote uptake of FP. Gender-transformative programming promotes gender equity and impacts behavior change. 6) Breakthroughs in novel contraceptives and systems improvement in family planning. Recent advances include user-centered contraceptive technologies that allow for self-administration and information systems which optimize supply chain management.

Conclusion

The research, advocacy, and programmatic abstracts at ICFP 2018 highlighted research advances, showcased implementation science wins, and provided evidence of critical knowledge gaps in global FP access and use
Econometrics and econometric modeling
Authors: Babeshko Lyudmila , Bich Mihail , Orlova Irina
Published: March 2021

The textbook covers a wide range of issues related to econometric modeling. Regression models are the core of econometric modeling, so the issues of their evaluation, testing of assumptions, adjustment and verification are given a significant place. Various aspects of multiple regression models are included: multicollinearity, dummy variables, and lag structure of variables. Methods of linearization and estimation of nonlinear models are considered. An apparatus for evaluating systems of simultaneous and apparently unrelated equations is presented. Attention is paid to time series models. Detailed solutions of the examples in Excel and the R software environment are included. Meets the requirements of the federal state educational standards of higher education of the latest generation. For undergraduate and graduate students studying in the field of "Economics", the curriculum of which includes the disciplines "Econometrics"," Econometric Modeling","Econometric research".
Islamic Finance in the CIS countries
Authors: Nagimova Al'mira
Published: March 2021

Over the past decades, Islamic finance has expanded its presence to many countries, including the former Soviet Union. It is not surprising that their expansion has become a subject of great interest for scientists, politicians, practitioners and the general public. How big is the market for Islamic finance in the post-Soviet region? Who are the main market players? What are their investment strategies here? Finally, what limits the development of the Islamic finance industry in the CIS countries? In this monograph, we try to answer these questions by examining a broad empirical base consisting of more than 1,000 transactions for the period from 1991 to 2020, as well as using a sociological approach. In addition, we assess the total volume of Islamic capital and identify the problems and prospects of this market in the CIS countries. It will be of interest to the management of banks, investment companies, funds, ministries, as well as to anyone interested in the world economy, international relations and the religious factor in the economy of post-Soviet countries.
Theory of operational-search activity
Authors: Ovchinskiy Vladimir
Published: March 2021

The textbook contains basic unclassified provisions of the theory of operational investigative activity, the study of which meets the requirements of the state standard of higher legal education. The fundamental works of scientists who have made a significant contribution to the formation and development of the theory of operational search activity are used. Meets the requirements of the federal state educational standards of higher education of the latest generation. For cadets and students of higher educational organizations of the law enforcement system, students studying in the direction of training 40.03.01 "Jurisprudence" (bachelor's level), graduate students and adjuncts, as well as for scientific and pedagogical workers and anyone interested in theoretical issues of operational investigative activities.
Perceived risk of COVID-19 acquisition and maternal mental distress
Authors: Sharifi-Heris Zahra , Moghasemi Sedigheh , Ghamsary Mark , Moodi Saba , Ghprbani Zainab , Amiri-Farahani Leila
Published: March 2021

Background

Pregnant women are a high-risk population for mental health effects during a pandemic.

Objective

This study aims to examine the association of perceived risk toward COVID-19 viral infection acquisition and maternal mental distress.

Methods

In a cross-sectional study, a total of 392 pregnant women were recruited. Data gathered using the perceived stress scale, State-Trait anxiety inventory, Beck depression inventory, and protective behaviour were assessed. Linear regression analysis was applied in both unadjusted and adjusted models to assess the association between the exposure and outcome variables.

Results

In all five unadjusted and adjusted models, the perceived risk of COVID-19 acquisition remained a highly significant predictor for stress, anxiety factor 1 and 2, depression, and protective behaviours (P<0.001).

Conclusion

COVID-19 may be an important additional stress source for pregnant women.
Using scheduling for health and wealth
Authors: Ratcliffe Jason
Published: March 2021

In this article, Jason Ratcliffe details how scheduling each day can lead to improved productivity in relation to education and business growth and leave time to spend alone or with family
Reactions of MoO2Cl2 and MoOCl4 with 2-Mercaptopyridine, 4-Phenylimidazole-2-thiol and 6-Mercaptopurine Monohydrate
Authors: Rani Deepika , Singh Gursharan , Sharma Seema
Published: March 2021

MoO2Cl2/MoOCl4 have been reacted with 4-phenylimidazole-2-thiol/6-mercaptopurine monohydrate/2-mercaptopyridine in acetonitrile solvent in unimolar/bimolar proportions at room temperature. The products thus obtained are: MoOCl3(C9H8N2S), [1]; Mo2O3Cl6(C9H7N2S)(CH3CN)2, [2]; Mo2O3Cl8(C9H7N2S)2(CH3CN)2, [3] and Mo2O4Cl4(C5H4NS-SN4C5), [4]. These products were studied by various techniques: infrared, proton NMR, liquid/gas chromatography-mass spectrometry, elemental analyses. Owing to the sensitivity of the products to air and moisture, the reactions and work ups were performed in vacuum line purged with oxygen by flushing dry nitrogen in it. Ions observed in mass spectrum are concurrent with the depicted formulae.
Study Rheological Behavior of Rapeseed Oils Compared to Mineral Oil
Authors: Stanciu Ioana
Published: March 2021

This article presents the dependence of dynamic temperature viscosity and shear rate for rapeseed oils used as biodegradable lubricant and SAE 10W. The studied rheograms show the dependence of the dynamic shear rate viscosity as well as the dependence of the dynamic temperature viscosity. From the rheograms there is a decrease in the dynamic viscosity with temperature and shear rate for the two oils. The dynamic viscosity of rapeseed oil is most strongly influenced by the shear rate compared to the studied SAE 10W oil. The rheological behavior of rapeseed and mineral oil SAE 10W was studied with the Haake VT 550 viscometer at temperatures between 40 and 1000C.
Biocatalytic Oxidation of Sulfides to Sulfones
Authors: Dhiman Shefali
Published: March 2021

This paper describes a method for the biocatalytic oxidation of sulfides. During the screening of microorganisms using pure cultures of Bacteria and Fungi for the oxidation of sulfides, it was observed that a number of strains of microorganisms, were able to oxidize various sulfides (1-4), but the desired sulfoxide was either not obtained or obtained only as a minor product. A close observation of the reaction showed complete oxidation and thus sulfone (5-8) formation had occurred in these cases.Sulfones are used to stabilize intermediates like α-radicals, α-anionsetc. and also used as cationic synthons in many known reactions.This prompted us to explore the sulfone synthesis by biocatalytic route.Approximately 20% of the strains tested (400 bacterial and 200 fungal) showed the formation of sulfone with conversion rate varying from 3 to 100% based on TLC analysis. There were two strains of fungi, Aspergillus ochraceus MTCC 5245 and Penicillium Funiculosum MTCC 5246 which showed excellent biocatalytic activity for oxidation sulfides to corresponding sulfones in high yield. In all these strains, the product was different from corresponding standard sulfoxide prepared by oxidation with m-chloroperbenzoic acid but well corresponded with the standard sample of sulfone prepared by oxidation of the corresponding sulfides with oxone®. The identity of sulfones in all cases was confirmed by 1H NMR.
Optimization method using nodal aberration theory for coaxial imaging systems with radial basis functions based on surface slope
Authors: Zhang Shuai , Xiao Liuchang , Zhao Xing , Song Lipei , Liu Yongji , Wang Lingjie , Shi Guangwei , Liu Weiwei
Published: March 2021

The radial basis functions based on the surface slope (RBF-Slope) freeform surfaces model has demonstrated stronger fitting ability and better optical performance than the conventional RBF model. However, the large number of basis functions and optimization variables of the RBF-Slope model may result in convergence problems during optimization for optical systems consisting of freeform surfaces characterized by RBF-Slope. To overcome these drawbacks, we use Zernike polynomials to link the RBF-Slope model to aberration correction and propose a new optimization method for coaxial imaging systems using the RBF-Slope model based on nodal aberration theory (NAT). The aberrations generated by the conic parameter and Zernike terms up to

Z

17

/

18

of the Zernike freeform surface at the non-stop surface in the coaxial imaging system are analyzed, and the gradient descent is implemented to obtain the optimal coefficients of the Zernike surface, which is then fitted by the RBF-Slope surface for further optimization. The method is applied to the optimization of a secondary mirror using the RBF-Slope model in a two-mirror telescope and proved to have better results than traditional commonly used direct optimization. This research offers an important reference for optimization using NAT and provides valuable insight into the optimization method for RBF-Slope freeform surfaces.
Direct demonstration of carrier distribution and recombination within step-bunched UV-LEDs
Authors: Xu Houqiang , Jiang Jiean , Chen Li , Hoo Jason , Yan Long , Guo Shiping , Shen Cai , Wei Yanping , Shao Hua , Zhang Zi-Hui , Guo Wei , Ye Jichun
Published: March 2021

AlGaN-based solid state UV emitters have many advantages over conventional UV sources. However, UV-LEDs still suffer from numerous challenges, including low quantum efficiency compared to their blue LED counterparts. One of the inherent reasons is a lack of carrier localization effect inside fully miscible AlGaN alloys. In the pursuit of phase separation and carrier localization inside the active region of AlGaN UV-LED, utilization of highly misoriented substrates proves to be useful, yet the carrier distribution and recombination mechanism in such structures has seldom been reported. In this paper, a UV-LED with step-bunched surface morphology was designed and fabricated, and the internal mechanism of high internal quantum efficiency was studied in detail. The correlation between microscale current distribution and surface morphology was provided, directly demonstrating that current prefers to flow through the step edges of the epitaxial layers. Experimental results were further supported by numerical simulation. It was found that efficient radiative recombination centers were formed in the inclined quantum well regions. A schematic three-dimensional energy band structure of the multiple quantum wells (MQWs) across the step was proposed and helps in further understanding the luminescence behavior of LEDs grown on misoriented substrates. Finally, a general principle to achieve carrier localization was proposed, which is valid for most ternary III-V semiconductors exhibiting phase separation.
Emerging high-level ciprofloxacin-resistant Salmonella enterica serovar typhi haplotype H58 in travelers returning to the Republic of Korea from India
Authors: Shin Eunkyung , Park Jungsun , Jeong Hyun Ju , Park Ae Kyung , Na Kyoungin , Lee Hyerim , Chun Jeong-hoon , Hwang Kyu Jam , Kim Chul-Joong , Kim Junyoung
Published: March 2021

In Korea, typhoid fever is a rare disease due to improved living standards. However, typhoid fever remains a major burden in developing countries and regions, such as India and Southeast Asia. In this study, we isolated Salmonella Typhi (S. Typhi) from eight patients with typhoid fever who were travelers returning from India. The strains isolated were characterized by antimicrobial susceptibility profiling and whole-genome sequencing (WGS) analysis. All strains were resistant to nalidixic acid and azithromycin. Among them, four isolates were highly resistant to ciprofloxacin (MIC ≥32 μg/ml); these strains have not been confirmed in Korea PulseNet DB. According to WGS, the ciprofloxacin-resistant strains belong to the global dominant multidrug-resistant (MDR) haplotype H58 (SNP glpA C1047T, SptP protein Q185* (premature stop codon)) and do not harbor the MDR plasmid. H58-associated SNPs in membrane and metabolism genes, including yhdA, yajI, hyaE, tryE, rlpB and metH, are present. Additionally, phylogenetic analysis assigned the H58 strains to sublineage II, whereas the non-H58 strains are closely related to haplotype H50. The presence of high-level ciprofloxacin-resistant S. Typhi haplotype H58 in Korea was first confirmed as due to influx from overseas via travelers. This study provides information about intercontinental drug-resistant transmission between countries and suggests that travelers need to be careful about personal hygiene.
Impact of the new heart allocation policy on patients with restrictive, hypertrophic, or congenital cardiomyopathies
Authors: Chouairi Fouad , Mullan Clancy W. , Sen Sounok , Mori Makoto , Fuery Michael , Elder Robert W. , Lesse Joshua , Norton Kelsey , Clark Katherine A. , Miller P. Elliott , Mulligan David , Formica Richard , Rogers Joseph G. , Jacoby Daniel , Maulion Christopher , Anwer Muhammad , Geirsson Arnar , Desai Nihar R. , Ahmad Tariq
Published: March 2021

Background

Patients with restrictive or hypertrophic cardiomyopathy (RCM/HCM) and congenital heart disease (CHD) do not derive clinical benefit from inotropes and mechanical circulatory support. Concerns were expressed that the new heart allocation system implemented in October 2018 would disadvantage these patients. This paper aimed to examine the impact of the new adult heart allocation system on transplantation and outcomes among patients with RCM/HCM/CHD.

Methods

We identified adult patients with RCM/HCM/CHD in the United Network for Organ Sharing (UNOS) database who were listed for or received a cardiac transplant from April 2017-June 2020. The cohort was separated into those listed before and after allocation system changes. Demographics and recipient characteristics, donor characteristics, waitlist survival, and post-transplantation outcomes were analyzed.

Results

The number of patients listed for RCM/HCM/CHD increased after the allocation system change from 429 to 517. Prior to the change, the majority RCM/HCM/CHD patients were Status 1A at time of transplantation; afterwards, most were Status 2. Wait times decreased significantly for all: RCM (41 days vs 27 days; P<0.05), HCM (55 days vs 38 days; P<0.05), CHD (81 days vs 49 days; P<0.05). Distance traveled increased for all: RCM (76 mi. vs 261 mi, P<0.001), HCM (88 mi. vs 231 mi. P<0.001), CHD (114 mi vs 199 mi, P<0.05). Rates of transplantation were higher for RCM and CHD (P<0.01), whereas post-transplant survival remained unchanged.

Conclusions

The new allocation system has had a positive impact on time to transplantation of patients with RCM, HCM, and CHD without negatively influencing survival.
Anoctamin 2-chloride channels reduce simple spike activity and mediate inhibition at elevated calcium concentration in cerebellar Purkinje cells
Authors: Auer Friederike , Franco Taveras Eliana , Klein Uli , Kesenheimer Céline , Fleischhauer Dana , Möhrlen Frank , Frings Stephan
Published: March 2021

Modulation of neuronal excitability is a prominent way of shaping the activity of neuronal networks. Recent studies highlight the role of calcium-activated chloride currents in this context, as they can both increase or decrease excitability. The calcium-activated chloride channel Anoctamin 2 (ANO2 alias TMEM16B) has been described in several regions of the mouse brain, including the olivo-cerebellar system. In inferior olivary neurons, ANO2 was proposed to increase excitability by facilitating the generation of high-threshold calcium spikes. An expression of ANO2 in cerebellar Purkinje cells was suggested, but its role in these neurons remains unclear. In the present study, we confirmed the expression of Ano2 mRNA in Purkinje cells and performed electrophysiological recordings to examine the influence of ANO2-chloride channels on the excitability of Purkinje cells by comparing wildtype mice to mice lacking ANO2. Recordings were performed in acute cerebellar slices of adult mice, which provided the possibility to study the role of ANO2 within the cerebellar cortex. Purkinje cells were uncoupled from climbing fiber input to assess specifically the effect of ANO2 channels on Purkinje cell activity. We identified an attenuating effect of ANO2-mediated chloride currents on the instantaneous simple spike activity both during strong current injections and during current injections close to the simple spike threshold. Moreover, we report a reduction of inhibitory currents from GABAergic interneurons upon depolarization, lasting for several seconds. Together with the role of ANO2-chloride channels in inferior olivary neurons, our data extend the evidence for a role of chloride-dependent modulation in the olivo-cerebellar system that might be important for proper cerebellum-dependent motor coordination and learning.
An expanded diversity of oomycetes in Carboniferous forests: Reinterpretation of Oochytrium lepidodendri (Renault 1894) from the Esnost chert, Massif Central, France
Authors: Strullu-Derrien Christine , Gèze Marc , Spencer Alan R. T. , De Franceschi Dario , Kenrick Paul , Selosse Marc-André , Knoll Andrew H.
Published: March 2021

335–330 million-year-old cherts from the Massif Central, France, contain exceptionally well-preserved remains of an early forest ecosystem, including plants, fungi and other microorganisms. Here we reinvestigate the original material prepared by Renault and Roche from collections of the Muséum National d’Histoire Naturelle, Paris, and present a re-evaluation of Oochytrium lepidodendri (Renault 1894), originally described as a zoosporic fungus. Confocal laser scanning microscopy (CLSM) was used to study the microfossils, enabling us in software to digitally reconstruct them in three-dimensional detail. We reinterpret O. lepidodendri as a pseudofungus and favour placement within the oomycetes, a diverse clade of saprotrophs and both animal and plant parasites. Phylogenetically, O. lepidodendri appears to belong to a group of oomycetes distinct from those previously described from Paleozoic rocks and most likely related to the Peronosporales s.l. This study adds to our knowledge of Paleozoic eukaryotic diversity and reinforces the view that oomycetes were early and diverse constituents of terrestrial biotas, playing similar ecological roles to those they perform in modern ecosystems.
Loss of childcare and classroom teaching during the Covid-19-related lockdown in spring 2020: A longitudinal study on consequences on leisure behavior and schoolwork at home
Authors: Poulain Tanja , Meigen Christof , Sobek Carolin , Ober Peggy , Igel Ulrike , Körner Antje , Kiess Wieland , Vogel Mandy
Published: March 2021

Aim

In spring 2020, the first Covid-19-related lockdown included the closing of kindergartens and schools. Home schooling, the lack of social contacts with peers and the care of the children at home posed an enormous challenge for many families.

Methods

The present study investigated the leisure behavior of 285 one- to 10-year-old German children at two time points (t1 and t2) during the Covid-19-related lockdown in spring 2020. In the subsample of primary school children (n = 102), we also explored children’s attitudes towards schoolwork at home. Analyses focused on the change of behavior from t1 to t2, on differences in these changes depending on socio-economic status (SES), and on associations of behavior with SES, the number of children at home, and the frequency of receiving learning materials from school.

Results

While the frequency of playing outside increased significantly from t1 to t2, the frequency of handicrafts, playing board games, indoor sports, and motivation to do schoolwork decreased. The observed changes between t1 and t2 did not differ depending on SES. However, a lower SES was associated with higher media use, less outdoor activity, and (though only marginally significant) a reduced time doing schoolwork and a reduced ability to concentrate on schoolwork at t1. In households with more children, children played outside more often, but were read to less frequently and (though only marginally significant) watched movies and series less frequently. Children receiving learning materials from school on a regular basis spent significantly more time doing schoolwork at home than children receiving materials only irregularly.

Conclusions

A continuing loss of childcare in day-care facilities and schools entails the danger of declining education in the form of (inter)active indoor activities and schoolwork.
Fine mapping epitope on Glycoprotein-Gn from Severe Fever with Thrombocytopenia Syndrome Virus
Authors: Moming Abulimiti , Shi Shen , Shen Shu , Qiao Jie , Yue Xihong , Wang Bo , Ding Juntao , Hu Zhihong , Deng Fei , Zhang Yujiang , Sun Surong
Published: March 2021

Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) was recently identified as a tick-borne pathogen that threat to human health. Since 2010, many countries including China, South Korea, and Japan have reported Human SFTS caused by SFTSV infection. The glycoprotein encoded by the SFTSV M gene is the major antigenic component on the viral surface, and responsible for the viral entry, which makes it an important viral antigen and a clinical diagnostic target. The present study aimed to map linear B cell epitopes (BCEs) on the N-terminal glycoprotein (Gn) from SFTSV strain WCH/97/HN/China/2011 using the modified biosynthetic peptide method. Five fine epitopes (E1, 196FSQSEFPD203; E2, 232GHSHKII238; E3, 256VCYKEGTGPC265; E4, 285FCKVAG290, and E5, 316SYGGM320) were identified using the rabbit antisera. Western blot analysis showed that all the five epitopes interacted with the positive serum of sheep that had been naturally infected with SFTSV. Three-dimensional structural modeling analysis showed that all identified BCEs were located on the surface of the SFTSV-Gn and contained flexible loops. The sequence alignment revealed high conservation of the identified BCEs among 13 SFTSV strains from different lineage. These mapped epitopes will escalate the understanding of the epitope distribution and pathogenic mechanism of SFTSV, and could provide a basis for the development of a SFTSV multi-epitope detection antigen.