bluuebunny/crossref_metadata_2025 huggingface dataset:
Remote electrical neuromodulation for acute treatment of migraine in adolescents
Authors: Hershey Andrew D. , Lin Tamar , Gruper Yaron , Harris Dagan , Ironi Alon , Berk Thomas , Szperka Christina L. , Berenson Frank
Published: December 2020

Objectives

Migraine is a common disabling neurological disorder. Current acute treatments for migraine in adolescents are mostly pharmacological and may have limited effectiveness, can cause side effects, and may lead to medication overuse. There is an unmet need for effective and well‐tolerated treatments. Remote electrical neuromodulation (REN) is a novel acute treatment of migraine that stimulates upper arm peripheral nerves to induce conditioned pain modulation (CPM)—an endogenous analgesic mechanism. The REN device (Nerivio®, Theranica Bio‐Electronics Ltd., Israel) is a FDA‐authorized device for acute treatment of migraine in adults. This study assessed the efficacy and safety of REN in adolescents with migraine.

Design and Methods

This was an open‐label, single‐arm, multicenter study in adolescents (ages 12–17 years) with migraine. Participants underwent a 4‐week run‐in phase. Eligible participants continued to an 8‐week treatment phase with the device. Pain severity, associated symptoms, and functional disability were recorded at treatment initiation, and 2 and 24 hours post‐treatment. The primary endpoints of this study were related to the safety and tolerability of REN. The secondary endpoints were related to device efficacy and included the proportion of participants who achieved pain relief at 2 hours post‐treatment and the proportion of participants who achieved pain freedom at 2 hours. The presented results reflect an interim analysis with subsequent stopping of the rest of the study.

Results

Sixty participants were enrolled for the study; of these, 14 failed to meet the run‐in criteria and 1 was lost to follow‐up. Forty‐five participants performed at least one treatment, of which 39 participants completed a test treatment with REN. One device‐related adverse event (2%) was reported in which a temporary feeling of pain in the arm was felt. Pain relief and pain‐free at 2 hours were achieved by 71% (28/39) and 35% (14/39) participants, respectively. At 2 hours, 69% (23/33) participants experienced improvement in functional ability.

Conclusions

REN may offer a safe and effective non‐pharmacological alternative for acute treatment in adolescents.
Short‐ and long‐term associations of atrial fibrillation catheter ablation with left atrial structure and function: A cardiac magnetic resonance study
Authors: Habibi Mohammadali , Lima Joao A. C. , Gucuk Ipek Esra , Spragg David , Ashikaga Hiroshi , Marine Joseph E. , Berger Ronald D. , Calkins Hugh , Nazarian Saman
Published: December 2020

Background

The effects of atrial fibrillation (AF) catheter ablation on the left atrium (LA) are poorly understood.

Objectives

To examine short‐ and long‐term associations of AF catheter ablation with LA function using cardiac magnetic resonance (CMR).

Methods

Fifty‐one AF patients (mean age 56 ± 8 years) underwent CMR at baseline, 1 day (n = 17) and 11 ± 2 months after ablation (n = 38). LA phasic volumes, emptying fractions (LAEF), and longitudinal strain were measured using feature‐tracking CMR. LA fibrosis was quantified using late gadolinium enhancement (LGE).

Results

There were no acute changes in volume; however, active, total LAEF, and peak LA strain decreased significantly compared to the baseline. During long‐term follow‐up, there was a decrease in maximum but not minimum LA volume (from 99 ± 5.2 ml to 89 ± 4.7 ml; p = .009) and a decrease in total LAEF (from 43 ± 1.8% to 39 ± 2.0%; p = .001). In patients with AF recurrence, LA volumes were unchanged. However, total LAEF decreased from 38 ± 3% to 33 ± 3%; p = .015. Patients without AF recurrence had no changes in LA functional parameters during follow‐up. The amount of LA LGE at long‐term follow‐up was higher compared to the baseline, however, was significantly less compared to immediately post‐procedure (37 ± 1.9% vs. 47 ± 2.8%; p = .015). A higher increase in LA LGE extent compared to the baseline was associated with a greater decrease in total LAEF (r = −.59; p < .001).

Conclusions

LA function is impaired acutely following AF catheter ablation. However, long‐term changes of LA function are associated positively with the successful restoration of sinus rhythm and inversely with increased LA LGE.
Same‐day opioid administration in opiate naïve patients is not associated with opioid‐induced esophageal dysfunction (OIED)
Authors: Balko Ryan A. , Katzka David A. , Murray Joseph A. , Alexander Jeffrey A. , Mara Kristin C. , Ravi Karthik
Published: December 2020

Background

Opioid‐induced esophageal dysfunction (OIED) is a recognized complication of chronic opioid use. However, the impact of acute opioid administration on esophageal motility remains unclear.

Methods

Opioid naïve patients with high‐resolution manometry (HRM) <480 min following esophagogastroduodenoscopy (EGD) (opioid‐HRM) and a control group with HRM <36 h prior to EGD between January 1, 2016, and November 10, 2018, from a single institution were identified. EGDs were performed exclusively with versed and fentanyl.

Key Results

One hundred and seventy‐four patients were identified, with 83 (47.7%) opioid‐HRM and 91 (52.3%) controls. Mean time from EGD to HRM was 229 (78–435) min. Baseline clinical features and HRM indications were similar between opioid‐HRM and controls. Chicago classification v3.0 defined HRM findings were similar between groups. Major motility disorders as defined by the Chicago classification v3.0 occurred at a similar frequency among opioid‐HRM and controls (27.7% vs. 36.3%, p = 0.23). Mean distal contractile integrity (DCI) was higher in opioid‐HRM (1939.3 ± 1318.9 vs. 1792.2 ± 2062.3 mmHg∙cm∙s, p = 0.043), but maximum DCI, distal latency, and integrated relaxation pressure did not differ between groups. Subgroup analysis assessing time and dose dependency did not identify differences in individual manometric parameters and Chicago classification v3.0 diagnosis between patients with HRM <240 min after EGD, >240 min after EGD, ≥125 mcg of IV fentanyl, <125 mcg IV fentanyl and controls.

Conclusions and Inferences

Same‐day acute opioid administration did not affect HRM findings in opioid naïve patients. Studies assessing the pathophysiology of and duration‐dependent relationship with opioids in OIED are needed.
Evaluation of baked egg oral immunotherapy in French children with hen's egg allergy
Authors: Gruzelle Vianney , Juchet Agnès , Martin‐Blondel Audrey , Michelet Marine , Chabbert‐Broue Anne , Didier Alain
Published: December 2020

Background

Introduction and gradual incremental escalation of a low dose of baked egg may accelerate the resolution of severe hen's egg (HE) allergy for some children. The purpose of our study was to evaluate the efficacy and safety of baked egg oral immunotherapy (OIT) in children with HE allergy after a low‐dose baked egg oral food challenge (OFC).

Methods

In a retrospective analysis of OFC performed between 2013 and 2018 at the Children's Hospital of Toulouse (France), we identified 71 children with HE allergy and high egg‐white (EW) and ovomucoid specific IgE levels, who underwent a total of 164 OFC (71 baked egg, then 93 unbaked egg). Mean age at first low‐dose baked egg OFC was 6 years. Median EW specific IgE was 14.0 kUA/L, and median ovomucoid specific IgE was 11.7 kUA/L.

Results

Most children were treated with baked egg OIT. Our study shows that 78.9% of the children did not react to first low‐dose baked egg OFC (702 mg of HE protein). 8.7% of children discontinued OIT at home. Finally, desensitization to unbaked HE was achieved in 47 children (66.2% of children allergic to HE). Children with lower EW specific IgE levels had a significantly higher probability of becoming desensitized to HE. We did not report any anaphylactic reactions to baked egg OIT.

Conclusion

Most children with HE allergy and high egg‐white (EW) and ovomucoïd specific IgE levels tolerate the introduction of baked egg. Baked egg OIT is safe, and anaphylaxis to baked egg OIT has not been observed.
Contribution of retrotrapezoid nucleus neurons to CO2‐amplified cardiorespiratory activity in spontaneously hypertensive rats
Authors: Tian Yanming , Geng Danyang , Wang Yakun , Shi Luo , Yu Hongxiao , He Wei , Zhu Yufang , Jun Shirui , Fu Congrui , Wang Xin , Zhang Xiangjian , Yuan Fang , Wang Sheng
Published: December 2020

Key points

This study demonstrates that both CO2‐induced respiratory and cardiovascular responses are augmented in spontaneously hypertensive rats (SHRs).

Genetic ablation of the retrotrapezoid nucleus (RTN) neurons depresses enhanced hypercapnic ventilatory response and eliminates CO2‐stimulated increase in arterial pressure and heart rate in SHRs.

SHRs have a high protein level of pH‐sensitive channels in the RTN, including the TASK‐2 channel, Kv12.1 channel and acid‐sensing ion channel 3.

The inhibition of putative TASK‐2 channel activity by clofilium diminishes amplified hypercapnic ventilatory and cardiovascular responses, and reduces the number of CO2‐activated RTN neurons in SHRs.

These results indicate that RTN neurons contribute to enhanced CO2‐stimulated respiratory and cardiovascular responses in SHRs.

The respiratory regulation of cardiovascular activity is essential for maintaining an efficient ventilation and perfusion ratio. Activation of central respiratory chemoreceptors not only elicits a ventilatory response but also regulates sympathetic nerve activity and arterial blood pressure (ABP). The retrotrapezoid nucleus (RTN) is the most completely characterized cluster of central respiratory chemoreceptors. We hypothesize that RTN neurons contribute to augmented CO2‐stimulated respiratory and cardiovascular responses in adult spontaneously hypertensive rats (SHRs). Our findings indicate that SHRs exhibit more enhanced hypercapnic cardiorespiratory responses than age‐matched normotensive Wistar–Kyoto rats. Genetic ablation of RTN neurons notably depresses an enhanced hypercapnic ventilatory response (HCVR) and eliminates a CO2‐stimulated greater increase in ABP and heart rate in SHRs. In addition, SHRs have a higher protein level of pH‐sensitive channels in the RTN, including TASK‐2 channels, Kv12.1 channels and acid‐sensing ion channel 3. Administration of clofilium (i.p.), an unselective inhibitor of TASK‐2 channels, not only significantly reduces the enhanced HCVR but also inhibits CO2‐amplified increases in ABP and heart rate in SHRs. Moreover, clofilium significantly decreases the number of CO2‐activated RTN neurons in SHRs. Taken together, we suggest that RTN neurons play an important role in enhanced hypercapnic ventilatory and cardiovascular responses in SHRs and the putative mechanism involved is associated with TASK‐2 channel activity in the RTN.
Responsabilidad del fiduciario en los contratos de comercialización de participaciones fiduciarias
Authors: Arce Ceicedo Eduardo
Published: December 2020

Las circulares 024 de 2016 y 07 de 2017 de la Superintendencia Financiera de Colombia modifican el régimen de responsabilidad del fiduciario en los negocios de comercialización de participaciones fiduciarias. La imposición de deberes de comportamiento específicos, la referencia a términos de la industria de fondos de inversión y el reconocimiento de un modelo de negocio con un diseño y un propósito diferente al original cambian el criterio de apreciación de la culpa y el alcance de responsabilidad. El presente artículo de reflexión pretende identificar los cambios que producen esas circulares en entendimientos tradicionales sobre la responsabilidad civil del fiduciario.
La transparencia y el interés público en el arbitraje de inversiones
Authors: Febles Pozo Nayiber
Published: December 2020

Resulta paradójico que las diferentes normas institucionales y arbitrales de que disponen las partes en litigio hayan sido tradicionalmente escasas con respecto a su transparencia procesal, al dejar, en gran medida, esas cuestiones a la discreción de las partes, o, a falta de acuerdo, al tribunal arbitral. Los problemas de procedimiento en el arbitraje internacional son cada día más frecuentes, de mayor complejidad y de máxima preocupación. Cuestiones estas que, junto al interés público, son objeto de interés en el presente artículo.
Hinges and Curved Lamina Emergent Torsional Joints in Cylindrical Developable Mechanisms
Authors: Seymour Kendall , Bilancia Pietro , Magleby Spencer , Howell Larry
Published: December 2020

Cylindrical developable mechanisms are devices that conform to and emerge from a cylindrical surface. These mechanisms can be formed or cut from the cylinder wall itself. This paper presents a study on adapting traditional hinge options to achieve revolute motion in these mechanisms. A brief overview of options is given, including classical pin hinges, small-length flexural pivots, initially curved beams, and an adaptation of the membrane thickness-accommodation technique. Curved lamina emergent torsional (LET) joints are then evaluated in detail, and a thin-walled modeling assumption is checked analytically and empirically. A small-scale cylindrical developable mechanism is then evaluated with Nitinol curved LET joints.
Sequence Evaluation and Comparative Analysis of Novel Assays for Intact Proviral HIV-1 DNA
Authors: Gaebler Christian , Falcinelli Shane D. , Stoffel Elina , Read Jenna , Murtagh Ross , Oliveira Thiago Y. , Ramos Victor , Lorenzi Julio C. C. , Kirchherr Jennifer , James Katherine S. , Allard Brigitte , Baker Caroline , Kuruc JoAnn D. , Caskey Marina , Archin Nancie M. , Siliciano Robert F. , Margolis David M. , Nussenzweig Michel C.
Published: December 2020

The intact proviral DNA assay (IPDA) and quadruplex PCR (Q4PCR) represent major advances in accurately quantifying and characterizing the replication-competent HIV reservoir. This study compares the two novel approaches for measuring intact HIV proviral DNA in samples from 39 antiretroviral therapy (ART)-suppressed people living with HIV, thereby informing ongoing efforts to deplete the HIV reservoir in cure-related trials.
Main parameters of SppC-based “linac-ring eA” and “ring-ring µA” colliders
Authors: Ketenoglu Bora
Published: December 2020

Concerning future lepton-nucleus colliders, International Linear Collider (ILC) and Plasma Wake Field Accelerator-Linear Collider (PWFA-LC) electrons in the order of 0.5 TeV and 5 TeV, respectively, colliding with Super proton–proton Collider (SppC)’s lead ions, are considered as “linac-ring eA” options. In addition, the 1.5 TeV option of the Muon Collider (MC) vs. 208Pb82+ ions of the SppC is also taken into account as a “ring-ring µA” collider. Luminosity values of the SppC-based eA and µA colliders are estimated. 3075 TeV lead parameters for the 100 km-circumference option of the SppC are taken into account to optimize luminosities of electron–nucleus and muon–nucleus collisions, keeping beam–beam effects and disruption in mind. It is shown that luminosities around 1030 cm−2 s−1 and 1032 cm−2 s−1 for eA and µA colliders, respectively, can be achieved by moderate upgrades of lepton and nucleus beam parameters.
Factors affecting the adoption of International Accounting Standards (IAS): Empirical evidence from Bangladesh
Authors: Moudud-Ul-Huq Syed , Biswas Tanmay , Chakraborty Brishti
Published: December 2020

This study aims to find the influential factors of adopting International Accounting Standards (IAS) in the banking industries of Bangladesh. This study is based on two-stage least-squares method for 561 unbalanced panel observations of 32 commercial banks in Bangladesh over the period from 2000 to 2018. To analyze the study, it uses macroeconomic and bank-level variables in which probability of IAS adoption, economic growth, and profitability are the main variables. The findings of the study indicate that economic growth has a significant relationship with IAS adoption in the banking industries of Bangladesh, as well as all variables relating to profitability affect IAS adoption excluding return on equity (ROE). SIZE and CAR do not influence IAS adoption from the bank-level variables, liquidity has a significant and negative relationship with IAS adoption and assets growth and total loan and advances (TLAs) have a significant impact on the IAS in banking industries of Bangladesh. The result of the study will be supportive to deliver precious information and unfathomable understanding as regards IAS and factors influencing IAS in banking sector. This is worthwhile to the researchers, students, and policy-makers while making critical decision about the adoption and implementation of IAS. Based on this study, it was suggested among others that adoption of IAS should to be a dynamic part of bank’s strategy because it upturns quality of reporting by increasing transparency, comparability, and acceptability.
Effects of Time-Varying Fluid on Dynamical Characteristics of Cantilever Beams: Numerical Simulations and Experimental Measurements
Authors: Shao Mingyu , Ma Chicheng , Hu Shuaizhao , Sun Chuansong , Jing Dong
Published: December 2020

In order to obtain the effects of time-varying fluid on dynamical characteristics of cantilever beams, this paper gives a comprehensive study of cantilever beams vibrating in a fluid with variable depth. The mathematical model of the cantilever beams in time-varying fluid is derived by combining Euler–Bernoulli beam theory and velocity potential theory, and the influence of the time-varying fluid is discussed. Then, a two-way fluid-structure interaction (FSI) numerical simulation procedure is proposed to calculate the transient responses of the beam. The validity and accuracy are verified according to the comparison among theoretical analysis, numerical simulations, and experimental measurements. Results show that, besides the added mass effect, a damping-like term is also induced due to the motion of the fluid, which is proportional to the moving velocity of the fluid. Both the added mass and the added damping increase with the increment of the width of the beam. The surrounding fluid near the free end affects the beam more significantly. As a negative damping is caused while the fluid decreases, resulting in a much slower decay of the time responses. Therefore, the added damping should not be neglected in the analysis of the FSI problems with time-varying fluid.
Interactive Classification of Whole-Slide Imaging Data for Cancer Researchers
Authors: Lee Sanghoon , Amgad Mohamed , Mobadersany Pooya , McCormick Matt , Pollack Brian P. , Elfandy Habiba , Hussein Hagar , Gutman David A. , Cooper Lee A.D.
Published: December 2020

Whole-slide histology images contain information that is valuable for clinical and basic science investigations of cancer but extracting quantitative measurements from these images is challenging for researchers who are not image analysis specialists. In this article, we describe HistomicsML2, a software tool for learn-by-example training of machine learning classifiers for histologic patterns in whole-slide images. This tool improves training efficiency and classifier performance by guiding users to the most informative training examples for labeling and can be used to develop classifiers for prospective application or as a rapid annotation tool that is adaptable to different cancer types. HistomicsML2 runs as a containerized server application that provides web-based user interfaces for classifier training, validation, exporting inference results, and collaborative review, and that can be deployed on GPU servers or cloud platforms. We demonstrate the utility of this tool by using it to classify tumor-infiltrating lymphocytes in breast carcinoma and cutaneous melanoma.

Significance:

An interactive machine learning tool for analyzing digital pathology images enables cancer researchers to apply this tool to measure histologic patterns for clinical and basic science studies.
Cancer Cell Fitness Is Dynamic
Authors: Lenz Luana S. , Faccioni Juliano L. , Bracco Paula A. , Santos Jephesson A.F. , Pereira Luiza C. , Buss Julieti H. , Tamborindeguy Mauricio T. , Torgo Daphne , Monteiro Thayana , Mantovani Giovana B. , Santo Carolina N. , Marcolin Julia C. , Dalsin Eloisa , Vigo Alvaro , Callegari-Jacques Sidia M. , Silva Andrew O. , Onzi Giovana R. , Begnini Karine R. , Lenz Guido
Published: December 2020

Several phenotypes that impact the capacity of cancer cells to survive and proliferate are dynamic. Here we used the number of cells in colonies as an assessment of fitness and devised a novel method called Dynamic Fitness Analysis (DynaFit) to measure the dynamics in fitness over the course of colony formation. DynaFit is based on the variance in growth rate of a population of founder cells compared with the variance in growth rate of colonies with different sizes. DynaFit revealed that cell fitness in cancer cell lines, primary cancer cells, and fibroblasts under unhindered growth conditions is dynamic. Key cellular mechanisms such as ERK signaling and cell-cycle synchronization differed significantly among cells in colonies after 2 to 4 generations and became indistinguishable from randomly sampled cells regarding these features. In the presence of cytotoxic agents, colonies reduced their variance in growth rate when compared with their founder cell, indicating a dynamic nature in the capacity to survive and proliferate in the presence of a drug. This finding was supported by measurable differences in DNA damage and induction of senescence among cells of colonies. The presence of epigenetic modulators during the formation of colonies stabilized their fitness for at least four generations. Collectively, these results support the understanding that cancer cell fitness is dynamic and its modulation is a fundamental aspect to be considered in comprehending cancer cell biology and its response to therapeutic interventions.

Significance:

Cancer cell fitness is dynamic over the course of the formation of colonies. This dynamic behavior is mediated by asymmetric mitosis, ERK activity, cell-cycle duration, and DNA repair capacity in the absence or presence of a drug.
Current Practices for Screening and Addressing Financial Hardship within the NCI Community Oncology Research Program
Authors: McLouth Laurie E. , Nightingale Chandylen L. , Dressler Emily V. , Snavely Anna C. , Hudson Matthew F. , Unger Joseph M. , Kazak Anne E. , Lee Simon J. Craddock , Edward Jean , Carlos Ruth , Kamen Charles S. , Neuman Heather B. , Weaver Kathryn E.
Published: December 2020

Background:

Cancer-related financial hardship is associated with poor care outcomes and reduced quality of life for patients and families. Scalable intervention development to address financial hardship requires knowledge of current screening practices and services within community cancer care.

Methods:

The NCI Community Oncology Research Program (NCORP) 2017 Landscape Assessment survey assessed financial screening and financial navigation practices within U.S. community oncology practices. Logistic models evaluated associations between financial hardship screening and availability of a cancer-specific financial navigator and practice group characteristics (e.g., safety-net designation, critical access hospital, proportion of racial and ethnic minority patients served).

Results:

Of 221 participating NCORP practice groups, 72% reported a financial screening process and 50% had a cancer-specific financial navigator. Practice groups with more than 10% of new patients with cancer enrolled in Medicaid (adjOR = 2.81, P = 0.02) and with less than 30% racial/ethnic minority cancer patient composition (adjOR = 3.91, P < 0.01) were more likely to screen for financial concerns. Practice groups with less than 30% racial/ethnic minority cancer patient composition (adjOR = 2.37, P < 0.01) were more likely to have a dedicated financial navigator or counselor for patients with cancer.

Conclusions:

Most NCORP practice groups screen for financial concerns and half have a cancer-specific financial navigator. Practices serving more racial or ethnic minority patients are less likely to screen and have a designated financial navigator.

Impact:

The effectiveness of financial screening and navigation for mitigating financial hardship could be tested within NCORP, along with specific interventions to address cancer care inequities.

See related commentary by Yabroff et al., p. 593
Phase I Study of MK-4166, an Anti-human Glucocorticoid-Induced TNF Receptor Antibody, Alone or with Pembrolizumab in Advanced Solid Tumors
Authors: Papadopoulos Kyriakos P. , Autio Karen , Golan Talia , Dobrenkov Konstantin , Chartash Elliot , Chen Qiusheng , Wnek Richard , Long Georgina V.
Published: December 2020

Purpose:

In this first-in-human phase I study (NCT02132754), we explored MK-4166 [humanized IgG1 agonist mAb targeting glucocorticoid-induced TNF receptor (GITR)] with and without pembrolizumab in advanced solid tumors.

Patients and Methods:

MK-4166 was tested alone (0.0015–900 mg i.v. every 3 weeks for four doses) or with pembrolizumab (200 mg i.v. every 3 weeks for ≤35 doses) in patients with metastatic solid tumors (dose escalation/confirmation) and advanced melanoma (expansion). Primary objectives were to evaluate the safety and tolerability and establish the MTD of MK-4166. Exploratory endpoints were objective response rate (ORR) and T cell–inflamed gene expression profile (GEP) analysis using RNA from baseline tumor samples.

Results:

A total of 113 patients were enrolled [monotherapy, n = 48; combination therapy, n = 65 (20 in the expansion)]. Forty-six patients (40.7%) had grade ≥3 adverse events, 9 (8.0%) of which were treatment related. No treatment-related deaths were observed. One dose-limiting toxicity event with monotherapy (bladder perforation in patient with neobladder) was considered related to study drug. MTD was not reached. MK-4166 pharmacodynamics showed decreased GITR availability on circulating T cells with increasing doses. One objective response (ORR, 2.2%) was achieved with combination therapy in the dose escalation/confirmation (n = 45). In the expansion, 8 of 13 patients with immune checkpoint inhibitor (ICI)-naïve melanoma achieved a response (ORR, 62%; 95% confidence interval, 32–86; 5 complete responses and 3 partial responses). None of the ICI-pretreated patients (n = 7) responded. High response rates were observed in ICI-naïve patients irrespective of GEP status.

Conclusions:

MK-4166 900 mg i.v. every 3 weeks as monotherapy and with pembrolizumab was tolerable. Responses were observed with combination therapy, mostly in patients with ICI-naïve melanoma.
177Lu-DOTA-EB-TATE, a Radiolabeled Analogue of Somatostatin Receptor Type 2, for the Imaging and Treatment of Thyroid Cancer
Authors: Thakur Shilpa , Daley Brianna , Millo Corina , Cochran Craig , Jacobson Orit , Lu Huiyan , Wang Zhantong , Kiesewetter Dale , Chen Xiaoyuan , Vasko Vasyl , Klubo-Gwiezdzinska Joanna
Published: December 2020

Purpose:

The goal of this study was to analyze the role of somatostatin receptor type 2 (SSTR2) as a molecular target for the imaging and treatment of thyroid cancer through analysis of SSTR2 expression and its epigenetic modulation and testing tumor uptake of different radiolabeled SSTR2 analogues.

Experimental Design:

We analyzed SSTR2 expression by immunostaining of 92 thyroid cancer tissue samples and quantified standard uptake values (SUVmax) of SSTR2 analogue, 68Ga-DOTA-TATE, by PET/CT imaging in 25 patients with metastatic thyroid cancer. We utilized human thyroid cancer cell lines characterized by differential SSTR2 expression (TT, BCPAP, and FTC133) and rat pancreatic cell line (AR42J) with intrinsically high SSTR2 expression for functional in vitro studies. SSTR2-high (AR42J) and SSTR2-low (FTC133) xenograft mouse models were used to test the uptake of radiolabeled SSTR2 analogues and their therapeutic efficacy in vivo.

Results:

Thyroid cancer had a higher SSTR2 expression than normal thyroid. Hurthle cell thyroid cancer was characterized by the highest 68Ga-DOTA-TATE uptake [median SUVmax, 16.5 (7.9–29)] than other types of thyroid cancers. In vivo studies demonstrated that radiolabeled DOTA-EB-TATE is characterized by significantly higher tumor uptake than DOTA-TATE (P < 0.001) and DOTA-JR11 (P < 0.001). Treatment with 177Lu-DOTA-EB-TATE extended survival and reduced tumor size in a mouse model characterized by high somatostatin (SST) analogues uptake (SUVmax, 15.16 ± 4.34), but had no effects in a model with low SST analogues uptake (SUVmax, 4.8 ± 0.27).

Conclusions:

A novel SST analogue, 177Lu-DOTA-EB-TATE, has the potential to be translated from bench to bedside for the targeted therapy of patients characterized by high uptake of SST analogues in metastatic lesions.
Postoperative Atrial Fibrillation and Long-Term Risk of Stroke in Patients Undergoing Liver Transplantation
Authors: Koshy Anoop N. , Enyati Anees , Weinberg Laurence , Han Hui-Chen , Horrigan Mark , Gow Paul J. , Ko Jefferson , Thijs Vincent , Testro Adam , Lim Han S. , Farouque Omar , Teh Andrew W.
Published: December 2020

Background and Purpose:

Postoperative atrial fibrillation (POAF) is the commonest cardiovascular complication following liver transplantation (LT). This study sought to assess a possible association of POAF with subsequent thromboembolic events in patients undergoing LT.

Methods:

A retrospective cohort study of consecutive adults undergoing LT between 2010 and 2018 was undertaken. Patients were classified as POAF if atrial fibrillation (AF) was documented within 30 days of LT without a prior history of AF. Cases of ischemic stroke or systemic embolism were adjudicated by a panel of 2 independent physicians.

Results:

Among the 461 patients included, POAF occurred in 47 (10.2%) a median of 3 days following transplantation. Independent predictors of POAF included advancing age, postoperative sepsis and left atrial enlargement. Over a median follow-up of 4.9 (interquartile range, 2.9–7.2) years, 21 cases of stroke and systemic embolism occurred. Rates of thromboembolic events were significantly higher in patients with POAF (17.0% versus 3.1%;
P
<0.001). After adjustment, POAF remained a strong independent predictor of thromboembolic events (hazard ratio, 8.36 [95% CI, 2.34–29.79]). Increasing CHA
2
DS
2
VASc score was also an independent predictor of thromboembolic events (hazard ratio, 1.58 [95% CI, 1.02–2.46]). A model using POAF and a CHA
2
DS
2
VASc score ≥2 alone yielded a C statistic of 0.77, with appropriate calibration for the prediction of thromboembolic events. However, POAF was not an independent predictor of long-term mortality.

Conclusions:

POAF following LT is associated with an 8-fold increased risk of thromboembolic events and the use of the CHA
2
DS
2
VASc score may facilitate risk stratification of these patients. Prospective studies are warranted to assess whether the use of oral anticoagulants can reduce the risk of thromboembolism following LT.
Multiobjective Evolutionary Algorithms Are Still Good: Maximizing
Monotone Approximately Submodular Minus Modular Functions
Authors: Qian Chao
Published: December 2020

As evolutionary algorithms (EAs) are general-purpose optimization algorithms, recent theoretical studies have tried to analyze their performance for solving general problem classes, with the goal of providing a general theoretical explanation of the behavior of EAs. Particularly, a simple multiobjective EA, that is, GSEMO, has been shown to be able to achieve good polynomial-time approximation guarantees for submodular optimization, where the objective function is only required to satisfy some properties and its explicit formulation is not needed. Submodular optimization has wide applications in diverse areas, and previous studies have considered the cases where the objective functions are monotone submodular, monotone non-submodular, or non-monotone submodular. To complement this line of research, this article studies the problem class of maximizing monotone approximately submodular minus modular functions (i.e., g-c) with a size constraint, where g is a so-called non-negative monotone approximately submodular function and c is a so-called non-negative modular function, resulting in the objective function (g-c) being non-monotone non-submodular in general. Different from previous analyses, we prove that by optimizing the original objective function (g-c) and the size simultaneously, the GSEMO fails to achieve a good polynomial-time approximation guarantee. However, we also prove that by optimizing a distorted objective function and the size simultaneously, the GSEMO can still achieve the best-known polynomial-time approximation guarantee. Empirical studies on the applications of Bayesian experimental design and directed vertex cover show the excellent performance of the GSEMO.
A new species of Leucostethus (Anura: Dendrobatidae) from the Cordillera Mache-Chindul in northwestern Ecuador, with comments on similar Colostethus and Hyloxalus
Authors: VIGLE GREGORY O. , COLOMA LUIS A. , SANTOS JUAN CARLOS , HERNANDEZ-NIETO SEBASTIAN , ORTEGA-ANDRADE H. MAURICIO , PALUH DANIEL J. , READ MORLEY
Published: December 2020

We describe a new species of dendrobatid frog, Leucostethus bilsa sp. nov., using molecular, morphological, and acoustic evidence. We also comment on the taxonomic status of four similar Hyloxalus and Colostethus. We provide an updated phylogeny of Leucostethus that corroborates previous hypotheses of relationships of nine species. Phylogenetic analysis using mitochondrial (i.e., 7095 bp of combined data from NADH1, NAHD2, cytochrome c oxidase I, cytochrome b and 12S-16S rRNA) and seven nuclear genes (i.e., 4739 bp) indicate a close relationship of L. bilsa to an undescribed species from Gorgona Island, Colombia, both of which apparently diverged in the Pliocene about 3 million years ago with about 6.25% (i.e., 146/2335 bp) differences for the section of 12S-16S mitochondrial fragment. Leucostethus bilsa is diurnal and riparian, characterized by distinctive bright mustard-yellow flash marks in the axillar and groin regions, posterior belly, and in the hindlimbs, the presence of dark gray lower labial stripe or marks, sexual dimorphism in ventral pattern, and by having male uniparental care. We describe its osteology and the male advertisement call, which is a series of peep notes. Osteological microCT images of representatives of each of the Colostethinae genera reveal a number of intriguing characters that may prove to be useful in phylogenetic studies. In terms of its distribution, Leucostethus bilsa is currently known only from a very small area within the Reserva Biológica Bilsa, located within the Cordillera Mache-Chindul in the Chocoan region of northwestern Ecuador, which was a Pliocene-Pleistocene refugium. This region is highly threatened with habitat degradation and remains as the last surviving refuge for a forest community known for a high proportion of endemic species of both flora and fauna.
Quality of Life Through the Prism of the Roy Adaptation Model
Authors: Almasloukh Khalid Bandar , Stewart Fahs Pamela
Published: December 2020

This concept analysis is to expand knowledge about quality of life within the Roy adaptation model. The Walker and Avant concept analysis methodology is utilized. The perception of life events influences quality of life, and quality of life influences decision-making and actions. Balance, self-esteem, and satisfaction are essentials of quality of life. The authors in this concept analysis provide a basis for further research studies measuring quality of life using the theoretical basis of the Roy adaptation model.
Development and validation of an artificial intelligence system for grading colposcopic impressions and guiding biopsies
Authors: Xue Peng , Tang Chao , Li Qing , Li Yuexiang , Shen Yu , Zhao Yuqian , Chen Jiawei , Wu Jianrong , Li Longyu , Wang Wei , Li Yucong , Cui Xiaoli , Zhang Shaokai , Zhang Wenhua , Zhang Xun , Ma Kai , Zheng Yefeng , Qian Tianyi , Ng Man Tat Alexander , Liu Zhihua , Qiao Youlin , Jiang Yu , Zhao Fanghui
Published: December 2020

Background

Colposcopy diagnosis and directed biopsy are the key components in cervical cancer screening programs. However, their performance is limited by the requirement for experienced colposcopists. This study aimed to develop and validate a Colposcopic Artificial Intelligence Auxiliary Diagnostic System (CAIADS) for grading colposcopic impressions and guiding biopsies.

Methods

Anonymized digital records of 19,435 patients were obtained from six hospitals across China. These records included colposcopic images, clinical information, and pathological results (gold standard). The data were randomly assigned (7:1:2) to a training and a tuning set for developing CAIADS and to a validation set for evaluating performance.

Results

The agreement between CAIADS-graded colposcopic impressions and pathology findings was higher than that of colposcopies interpreted by colposcopists (82.2% versus 65.9%, kappa 0.750 versus 0.516,p < 0.001). For detecting pathological high-grade squamous intraepithelial lesion or worse (HSIL+), CAIADS showed higher sensitivity than the use of colposcopies interpreted by colposcopists at either biopsy threshold (low-grade or worse 90.5%, 95% CI 88.9–91.4% versus 83.5%, 81.5–85.3%; high-grade or worse 71.9%, 69.5–74.2% versus 60.4%, 57.9–62.9%; allp < 0.001), whereas the specificities were similar (low-grade or worse 51.8%, 49.8–53.8% versus 52.0%, 50.0–54.1%; high-grade or worse 93.9%, 92.9–94.9% versus 94.9%, 93.9–95.7%; allp > 0.05). The CAIADS also demonstrated a superior ability in predicting biopsy sites, with a median mean-intersection-over-union (mIoU) of 0.758.

Conclusions

The CAIADS has potential in assisting beginners and for improving the diagnostic quality of colposcopy and biopsy in the detection of cervical precancer/cancer.
May the analysis of 1918 influenza pandemic give hints to imagine the possible magnitude of Corona Virus Disease-2019 (COVID-19)?
Authors: Scarpa Raffaele , Caso Francesco , Costa Luisa , Passavanti Saverio , Vitale Maria Grazia , Trojaniello Claudia , Del Puente Antonio , Ascierto Paolo A.
Published: December 2020

Background

In 1918 an unknown infectious agent spread around the world infecting over one-third of the general population and killing almost 50 million people. Many countries were at war, the First World War. Since Spain was a neutral country and Spanish press could report about the infection without censorship, this condition is commonly remembered as “Spanish influenza”. This review examines several aspects during the 1918 influenza pandemic to bring out evidences which might be useful to imagine the possible magnitude of the present coronavirus disease 2019 (COVID-19).

Methods

In the first part of this review we will examine the origin of the SARS-Coronavirus-2 and 1918 Spanish Influenza Virus and the role played by host and environment in its diffusion. We will also include in our analysis an evaluation of different approaches utilized to restrain the spread of pandemic and to treat infected patients. In the second part, we will try to imagine the magnitude of the present COVID-19 pandemic and the possible measures able to restrain in the present environment its spread.

Results

Several factors characterize the outcome in a viral pandemic infection. They include the complete knowledge of the virus, the complete knowledge of the host and of the environment where the host lives and the pandemic develops.

Conclusion

By comparing the situation seen in 1918 with the current one, we are now in a more favourable position. The experience of the past teaches us that their success is linked to a rapid, constant and lasting application. Then, rather than coercion, awareness of the need to observe such prevention measures works better.
ПАРАЗИТИРОВАНИЕ В ИНТЕРНЕТ-КОММЕРЦИИ: ЭМПИРИЧЕСКИЙ АНАЛИЗ
Authors: Mityashin Gleb Yurievich , Katrashova Yuliya Valentinovna
Published: December 2020

В статье рассмотрен феномен паразитирования, представляющий собой покупку потребителем товара, после проверки его потребительских качеств в традиционном магазине. Описаны разновидности данного феномена: межфирменное и внутрифирменное паразитирование. Для получения более детальной информации о феномене паразитирования в интернет-коммерции авторами был проведен опрос, наглядно демонстрирующий поведение потребителей при покупке товаров в интернете. В заключении сформулированы рекомендации, позволяющие минимизировать негативное влияние данного феномена.Цель исследования: выявить существование феномена паразитирования в интернет-коммерции и предложить возможные варианты борьбы с ним.Метод или методология проведения работы: метод анкетирования, метод формализации, метод анализа и синтеза, метод описания.Результаты: обосновано существование феномена паразитирования в интернет-коммерции и сформулированы рекомендации, позволяющие снизить его негативный эффект.Область применения результатов: полученные результаты целесообразно применять управляющим розничными торговыми предприятиями для повышения эффективности их деятельности путем минимизации негативного влияния феномена паразитирования в интернет-коммерции.
Formation of Competencies of Heads for Management of Digital Culture Devel-opment of Employees of Educational Organizations
Authors: Shafranova O.
Published: December 2020

In the conditions of the intensive transformation of modern culture, due to the mass dig-italization of various spheres of society, the traditional education-culture relationship acquires significant features. A significant cultural layer (especially mass culture) is formed in the digital environment. Today's education requires that all subjects of the educational process not only correctly use the artifacts of this culture, but also successfully participate in its creation. One of the key conditions for solving this problem is the formation of a digital culture of employees of the educational organization. And effective management of the development of such a culture becomes an important managerial task of its leader. Of course, such a task requires the head of special competencies, which can be mastered by an effective system of continuing education of the education manager.
SPATIAL AND TEMPORAL VARIATIONS OF K Ca II LINE PROFILE SHAPES IN DIFFERENT STRUCTURES OF THE SOLAR CHROMOSPHERE. II. DETERMINATION TECHNIQUE AND CORRELATION RELATIONSHIPS BETWEEN THE K CA II LINE PARAMETERS FOR K1 AND K2 FEATURES
Authors: Turova Irina , Grigoryeva Sofiya , Ozhogina Olga
Published: December 2020

We have studied two regions located at the base of a coronal hole. For the K₁ intensity minima and K₂ peaks, which form between the upper photosphere and the lower chromosphere and in the lower chromosphere respectively, a number of Ca II line parameters have been computed. We have improved the determination technique for ∆λᴋ₁ᵥ and ∆λᴋ₁ᵣ, ∆λᴋ₂ᵥ and ∆λᴋ₂ᵣ line profile shifts, including certain cases when their direct determination was complicated. We have determined Iᴋ₁ᵥ, Iᴋ₁ᵣ, Iᴋ₂ᵥ, Iᴋ₂ᵣ intensities, K₁ minima and K₂ peaks separations SEPᴋ₁ = ∆λᴋ₁ᵣ – ∆λᴋ₁ᵥ, SEPᴋ₂ = ∆λᴋ₂ᵣ – ∆λᴋ₂ᵥ, respectively. We have constructed scatter plots and have computed correlation relationships between parameters relating to different levels of atmosphere.

We have obtained the following results.

The intensities observed in the lower and middle chromosphere are connected closer than intensities related to the upper photosphere and middle chromosphere.

The structures with a stronger magnetic field are brighter at the upper photosphere and lower chromosphere levels as compared to the structures with a weaker magnetic field.

K₁ minima separations are of greater value for the structures with a stronger magnetic field relative to the structures with a weaker magnetic field, whereas K₂ peaks separations demonstrate the opposite behavior. They are lower for the structures with a stronger magnetic field. It is true not only for the chosen structures belonging to quiet regions but also for the plage, though we need additional statistics for plages.

The relation between shifts of K₁ minima and K₂ peak intensities for violet and red wings appeared to be weak. This may be due to the considerable contribution of random movements to the velocity field at the upper photosphere and lower chromosphere levels or due to different forming levels for the profile violet and red wings.
Spatial and temporal variations of K CA II line profile shapes in different structures of the solar chromosphere. II. Determination technique and correlation relationships between the K CA II line parameters for K₁ and K₂ features
Authors: Turova Irina , Grigoryeva Sofiya , Ozhogina Olga
Published: December 2020

We have studied two regions located at the base of a coronal hole. For the K₁ intensity minima and K₂ peaks, which form between the upper photosphere and the lower chromosphere and in the lower chromosphere respectively, a number of Ca II line parameters have been computed. We have improved the determination technique for ∆λᴋ₁ᵥ and ∆λᴋ₁ᵣ, ∆λᴋ₂ᵥ and ∆λᴋ₂ᵣ line profile shifts, including certain cases when their direct determination was complicated. We have determined Iᴋ₁ᵥ, Iᴋ₁ᵣ, Iᴋ₂ᵥ, Iᴋ₂ᵣ intensities, K₁ minima and K₂ peaks separations SEPᴋ₁ = ∆λᴋ₁ᵣ – ∆λᴋ₁ᵥ, SEPᴋ₂ = ∆λᴋ₂ᵣ – ∆λᴋ₂ᵥ, respectively. We have constructed scatter plots and have computed correlation relationships between parameters relating to different levels of atmosphere.

We have obtained the following results.

The intensities observed in the lower and middle chromosphere are connected closer than intensities related to the upper photosphere and middle chromosphere.

The structures with a stronger magnetic field are brighter at the upper photosphere and lower chromosphere levels as compared to the structures with a weaker magnetic field.

K₁ minima separations are of greater value for the structures with a stronger magnetic field relative to the structures with a weaker magnetic field, whereas K₂ peaks separations demonstrate the opposite behavior. They are lower for the structures with a stronger magnetic field. It is true not only for the chosen structures belonging to quiet regions but also for the plage, though we need additional statistics for plages.

The relation between shifts of K₁ minima and K₂ peak intensities for violet and red wings appeared to be weak. This may be due to the considerable contribution of random movements to the velocity field at the upper photosphere and lower chromosphere levels or due to different forming levels for the profile violet and red wings.
Uso del smartphone en jóvenes universitarios: una oportunidad para el aprendizaje
Authors: Dafonte Gómez Alberto , Fabián Maina Marcelo , García Crespo Oswaldo
Published: December 2020

El elevado nivel de penetración del smartphone junto con su reducido coste de implementación en el ámbito educativo hace que el m-learning sea una tendencia en crecimiento a nivel mundial. Este artículo presenta los hábitos de uso de aplicaciones para la comunicación y el aprendizaje móvil del alumnado de educación superior e identifica factores que pueden favorecer la intención de adoptar herramientas de m-learning basadas en el smartphone entre el alumnado universitario. Para ello se administró un cuestionario basado en el modelo UTAUT2 de adopción de tecnología a 176 estudiantes de distintos cursos del Grado en Publicidad y Relaciones Públicas de la Universidad de Vigo. Los resultados muestran los principales usos que hacen los estudiantes del smartphone, sus preferencias en cuanto a la utilización del dispositivo para el aprendizaje y la importancia de la dimensión lúdica del m-learning en la intención de adoptar este modelo, un aspecto que no muchas investigaciones del campo destacan, pero que convenientemente utilizado por los docentes– puede suponer una gran oportunidad para su implementación.