bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-exome Sequencing in Penile Squamous Cell Carcinoma Uncovers Novel Prognostic Categorization and Drug Targets Similar to Head and Neck Squamous Cell Carcinoma
Authors: Chahoud Jad , Gleber-Netto Frederico O. , McCormick Barrett Z. , Rao Priya , Lu Xin , Guo Ming , Morgan Maggaret B. , Chu Randy A. , Martinez-Ferrer Magaly , Eterovic Agda Karina , Pickering Curtis R. , Pettaway Curtis A. 
Published: January 2021

Abstract

Purpose:
Penile squamous cell carcinoma (PSCC) is rare with limited treatment options. We report the first whole-exome sequencing (WES) analysis and compare the molecular landscape of PSCC with other squamous cell carcinomas (SCC), with the goal to identify common novel targets.

Experimental Design:
PSCC and matched normal penile tissues from 34 prospectively followed patients, underwent genomic WES and human papilloma virus testing. We performed tumor mutation signature estimation by two methods, first to identify APOBEC-related mutation enrichments and second to classify PSCC-enriched mutational patterns based on their association with the Catalogue of Somatic Mutations in Cancer mutation signatures. We performed an extensive genomic comparison between our PSCC cohort and other SCCs in The Cancer Genome Atlas studies.

Results:
We identified that most PSCC samples showed enrichment for Notch pathway (n = 24, 70.6%) alterations, comparable with head and neck squamous cell carcinoma (HNSC). PSCC mutation signatures are most comparable with HNSC signatures. PSCC samples showed an enrichment of two distinct mutational signatures, the first, associated with oncogenic activity of AID/APOBEC, and the second, associated with defective DNA mismatch repair and microsatellite instability. MP1 enrichment was positively correlated with increased tumor mutation burden (TMB; CC, 0.71; P &lt; 0.0001) and correlated with significantly worse survival in comparison with those with the MP2 subset [HR, 10.2 (1.13–92.9); P = 0.039]. We show that a subset of PSCC (38%), with enrichment of APOBEC-related mutation signature, had significantly higher TMB and worse overall survival in comparison with non-APOBEC–enriched subset [HR, 2.41 (1.11–6.77); P = 0.042].

Conclusions:
This study identified novel druggable targets and similarities in mutational signatures between PSCC and HNSC with potential clinical implications.
See related commentary by McGregor and Sonpavde, p. 2375
АНАЛІЗ ПРОФЕСІЙНОЇ ЕТИКИ ТА РОЛІ РОБОТИ СЕРЕДНЬОГО МЕДИЧНОГО ПЕРСОНАЛУ
Authors: Lykha L. M. , Hospodarskyy I. Ya. 
Published: January 2021

Глобалізаційні та інтеграційні процеси в суспільстві, динамічний розвиток медичних технологій, визнання світовою спільнотою проблеми фізичного, морального і соціального здоров’я як головного показника соціально-економічної зрілості, культури й успішності держави, соціальний запит на якість медичних послуг зумовлюють особливі вимоги до професійної діяльності середнього медичного персоналу загалом і медичних сестер зокрема. Медична сестра повинна успішно володіти фундаментальними та спеціальними знаннями й уміннями в питаннях комплексного догляду за пацієнтами, надавати медичну допомогу, що відповідає принципу гуманності, національним і світовим професійним стандартам, активно здійснювати профілактичну діяльність у сфері охорони здоров’я. У виконанні своїх фахових обов’язків медична сестра має керуватися нормами професійної моралі й етики.
Важливість професійних та особистісних рис актуалізує необхідність удосконалення змісту формування професійної етики майбутніх медичних сестер у навчально-виховному процесі, зокрема під час вивчення дисциплін соціально-гуманітарної, психолого-педагогічної, професійно-практичної підготовки, проведення навчально-дослідної, виховної роботи, виробничих практик, що визначено галузевими стандартами вищої медичної освіти.
ОСОБЛИВОСТІ ДИСТАНЦІЙНОГО НАВЧАННЯ СТУДЕНТІВ В УМОВАХ ПАНДЕМІЇ COVID-19 (ЗА РЕЗУЛЬТАТАМИ АНКЕТУВАННЯ)
Authors: Terenda N. O. , Terenda О. А. , Horishnyi M. I. , Panchyshyn N. Ya. 
Published: January 2021

У статті проаналізовано результати онлайн-анкетування студентів щодо їхнього ставлення до переваг та недоліків дистанційної форми навчання. В умовах пандемії COVID-19 дистанційне навчання є однією з провідних світових тенденцій в освіті. Ця технологія реалізує принцип безперервної освіти і здатна задовольнити постійно зростаючий попит на знання в інформаційному суспільстві. Отримані результати онлайн-анкетування студентів вказують на існування суб’єктивних перешкод у здобутті знань під час дистанційного навчання, яке передбачає значну самомотивацію студента щодо власного навчання, а також високий рівень самоорганізації. Для покращення доступності навчально-методичних матеріалів, збільшення контакту між викладачем і студентом необхідно залучати інтерактивні платформи, які дозволять покращити процес викладання та засвоєння необхідного навчального матеріалу.
Широке запровадження дистанційної форми освіти у 2020 р., зумовлене поширенням пандемії COVID-19 та необхідністю дотримання всіх карантинних заходів задля збереження здоров’я та життя всіх учасників освітнього процесу, поставило нові виклики перед здобувачами вищої освіти, подолати які необхідно спільними зусиллями всіх зацікавлених сторін із залученням новітніх інтерактивних платформ, та підвищення мотиваційного фактора у здобутті нових знань.
Genetic Risk Score to Identify Risk of Venous Thromboembolism in Patients With Cardiometabolic Disease
Authors: Marston Nicholas A. , Melloni Giorgio E.M. , Gurmu Yared , Bonaca Marc P. , Kamanu Frederick K. , Roselli Carolina , Lee Christina , Cavallari Ilaria , Giugliano Robert P. , Scirica Benjamin M. , Bhatt Deepak L. , Steg Philippe Gabriel , Cohen Marc , Storey Robert F. , Keech Anthony C. , Raz Itamar , Mosenzon Ofri , Braunwald Eugene , Lubitz Steven A. , Ellinor Patrick T. , Sabatine Marc S. , Ruff Christian T. 
Published: January 2021

Background:
Venous thromboembolism (VTE) is a major cause of cardiovascular morbidity and mortality and has a known genetic contribution. We tested the performance of a genetic risk score for its ability to predict VTE in 3 cohorts of patients with cardiometabolic disease.

Methods:
We included patients from the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk), PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin), and SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus) trials (history of a major atherosclerotic cardiovascular event, myocardial infarction, and diabetes, respectively) who consented for genetic testing and were not on baseline anticoagulation. We calculated a VTE genetic risk score based on 297 single nucleotide polymorphisms with established genome-wide significance. Patients were divided into tertiles of genetic risk. Cox proportional hazards models were used to calculate hazard ratios for VTE across genetic risk groups. The polygenic risk score was compared with available clinical risk factors (age, obesity, smoking, history of heart failure, and diabetes) and common monogenic mutations.

Results:

A total of 29 663 patients were included in the analysis with a median follow-up of 2.4 years, of whom 174 had a VTE event. There was a significantly increased gradient of risk across VTE genetic risk tertiles (
P
-trend <0.0001). After adjustment for clinical risk factors, patients in the intermediate and high genetic risk groups had a 1.88-fold (95% CI, 1.23–2.89;
P
=0.004) and 2.70-fold (95% CI, 1.81–4.06;
P
<0.0001) higher risk of VTE compared with patients with low genetic risk. In a continuous model adjusted for clinical risk factors, each standard deviation increase in the genetic risk score was associated with a 47% (95% CI, 29–68) increased risk of VTE (
P
<0.0001).

Conclusions:
In a broad spectrum of patients with cardiometabolic disease, a polygenic risk score is a strong, independent predictor of VTE after accounting for available clinical risk factors, identifying 1/3 of patients who have a risk of VTE comparable to that seen with established monogenic thrombophilia.
Rationale and Design of the SAFE-PAD Study
Authors: Secemsky Eric A. , Raja Aishwarya , Shen Changyu , Valsdottir Linda R. , Schermerhorn Marc , Yeh Robert W. ,   on behalf of the SAFE-PAD Investigators
Published: January 2021

Background:
Recent evidence from randomized controlled trials has raised concerns about the long-term safety of paclitaxel-coated peripheral devices used for femoropopliteal artery revascularization. In response to a call for more real-world data on the safety of these devices, the SAFE-PAD study (Safety Assessment of Femoropopliteal Endovascular treatment with Paclitaxel-coated Devices) was designed with input from the Food and Drug Administration to provide a long-term, comprehensive evaluation of the mortality risk associated with paclitaxel-coated devices among Medicare beneficiaries.

Methods and Results:

SAFE-PAD is an observational cohort study of fee-for-service Medicare beneficiaries that underwent femoropopliteal artery revascularization with either a drug-coated device or nondrug-coated device from 2015 through 2018. All patients age 66 years or older who underwent revascularization will be identified using a combination of
International Classification of Diseases, Tenth Revision
procedural codes, Current Procedural Terminology codes, and Healthcare Common Procedure Coding System C-codes. The safety end point of all-cause death will be updated semiannually and continued until the median duration of follow-up surpasses 5 years. Sub-group analyses will be conducted by device type, patient characteristics, and procedural setting.

Registration:

The SAFE-PAD study has been registered on URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04496544.

Conclusions:
The SAFE-PAD study will evaluate the long-term safety of drug-coated devices compared with nondrug-coated devices for femoropopliteal artery revascularization among a broad, real-world population of patients with peripheral artery disease.
Aberrant Activation of Notch1 Signaling in Glomerular Endothelium Induces Albuminuria
Authors: Li Liqun , Liu Qiang , Shang Tongyao , Song Wei , Xu Dongmei , Allen Thaddeus D. , Wang Xia , Jeong James , Lobe Corrinne G. , Liu Ju 
Published: January 2021

Rationale:
Glomerular capillaries are lined with a highly specialized fenestrated endothelium and contribute to the glomerular filtration barrier. The Notch signaling pathway is involved in regulation of glomerular filtration barrier, but its role in glomerular endothelium has not been investigated due to the embryonic lethality of animal models with genetic modification of Notch pathway components in the endothelium.

Objective:
To determine the effects of aberrant activation of the Notch signaling in glomerular endothelium and the underlying molecular mechanisms.

Methods and Results:

We established the
ZEG-NICD1 (notch1 intracellular domain)/Tie2-tTA/Tet-O-Cre
transgenic mouse model to constitutively activate Notch1 signaling in endothelial cells of adult mice. The triple transgenic mice developed severe albuminuria with significantly decreased VE-cadherin (vascular endothelial cadherin) expression in the glomerular endothelium. In vitro studies showed that either NICD1 (Notch1 intracellular domain) lentiviral infection or treatment with Notch ligand DLL4 (delta-like ligand 4) markedly reduced VE-cadherin expression and increased monolayer permeability of human renal glomerular endothelial cells. In addition, Notch1 activation or gene knockdown of VE-cadherin reduced the glomerular endothelial glycocalyx. Further investigation demonstrated that activated Notch1 suppression of
VE-cadherin
was through the transcription factors SNAI1 (snail family transcriptional repressor 1) and ERG (Ets related gene), which bind to the −373 E-box and the −134/−118 ETS (E26 transformation-specific) element of the VE-cadherin promoter, respectively.

Conclusions:
Our results reveal novel regulatory mechanisms whereby endothelial Notch1 signaling dictates the level of VE-cadherin through the transcription factors SNAI1 and ERG, leading to dysfunction of glomerular filtration barrier and induction of albuminuria.

Graphic Abstract:

A
graphic abstract
is available for this article.
Prognostic Value of Abdominal Aortic Calcification: A Systematic Review and Meta‐Analysis of Observational Studies
Authors: Leow Kevin , Szulc Pawel , Schousboe John T. , Kiel Douglas P. , Teixeira‐Pinto Armando , Shaikh Hassan , Sawang Michael , Sim Marc , Bondonno Nicola , Hodgson Jonathan M. , Sharma Ankit , Thompson Peter L. , Prince Richard L. , Craig Jonathan C. , Lim Wai H. , Wong Germaine , Lewis Joshua R. 
Published: January 2021

Background
The prognostic importance of abdominal aortic calcification (AAC) viewed on noninvasive imaging modalities remains uncertain.

Methods and Results
We searched electronic databases (MEDLINE and Embase) until March 2018. Multiple reviewers identified prospective studies reporting AAC and incident cardiovascular events or all‐cause mortality. Two independent reviewers assessed eligibility and risk of bias and extracted data. Summary risk ratios (RRs) were estimated using random‐effects models comparing the higher AAC groups combined (any or more advanced AAC) to the lowest reported AAC group. We identified 52 studies (46 cohorts, 36 092 participants); only studies of patients with chronic kidney disease (57%) and the general older‐elderly (median, 68 years; range, 60–80 years) populations (26%) had sufficient data to meta‐analyze. People with any or more advanced AAC had higher risk of cardiovascular events (RR, 1.83; 95% CI, 1.40–2.39), fatal cardiovascular events (RR, 1.85; 95% CI, 1.44–2.39), and all‐cause mortality (RR, 1.98; 95% CI, 1.55–2.53). Patients with chronic kidney disease with any or more advanced AAC had a higher risk of cardiovascular events (RR, 3.47; 95% CI, 2.21–5.45), fatal cardiovascular events (RR, 3.68; 95% CI, 2.32–5.84), and all‐cause mortality (RR, 2.40; 95% CI, 1.95–2.97).

Conclusions
Higher‐risk populations, such as the elderly and those with chronic kidney disease with AAC have substantially greater risk of future cardiovascular events and poorer prognosis. Providing information on AAC may help clinicians understand and manage patients' cardiovascular risk better.
<p><strong>Four new species of monoraphid diatoms from Western Sichuan Plateau in China</strong></p>
Authors: YOU Q.M. , ZHAO K. , WANG Y.L. , YU P. , KOCIOLEK J.P. , PANG W.T. , WANG Q.X. 
Published: January 2021

Four new monoraphid diatoms are examined and described from a high-altitude (> 3000 m) region of western Sichuan, China. The descriptions are based on light and scanning electron microscopy observations, and the four new species are compared with similar taxa worldwide. Achnanthidium sichuanense sp. nov. has small, lanceolate-elliptical valves, with rounded apices. The outline and central area differentiate it from similar species. The unique characteristic of Eucocconeis undulatum sp. nov. is that it has valves that are undulate along the apical axis, forming an “H”-shaped area on both raphe and rapheless valves as seen in light microscope (LM). Platessa mugecuonesis sp. nov. and Platessa lanceolata sp. nov. are two small species, whose valve outlines and central areas make them different from other species in this genus. A. sichuanense sp. nov. and E. undulatum sp. nov. are discussed in terms of the relationship between “Achnanthidium & Psammothidium” and “Eucocconeis & Psammothidium”, as these genera are difficult to separate according to morphological characteristics.
Convection–Kelvin Wave Coupling in a Global Convection-Permitting Model
Authors: Weber Nicholas J. , Kim Daehyun , Mass Clifford F. 
Published: January 2021

AbstractA convectively coupled equatorial Kelvin wave (CCKW) was observed over the equatorial Indian Ocean in early November 2011 during the DYNAMO field campaign. This study examines the structure of the CCKW event using two simulations made using the MPAS model: one with 3-km grid spacing without convective parameterization and another with a 15-km grid and parameterized convection. Both simulations qualitatively capture the observed structure of the CCKW, including its vertical tilt and progression of cloud/precipitation structures. The two simulations, however, differ substantially in the amplitude of the CCKW-associated precipitation. While the 3-km run realistically captures the observed modulation of precipitation by the CCKW, the 15-km simulation severely underestimates its magnitude. To understand the difference between the two MPAS simulations regarding wave–convection coupling within the CCKW, the relationship of precipitation with convective inhibition, saturation fraction, and surface turbulent fluxes is investigated. Results show that the 15-km simulation underestimates the magnitude of the CCKW precipitation peak in association with its unrealistically linear relationship between moisture and precipitation. Precipitation, both in observations and the 3-km run, is predominantly controlled by saturation fraction and this relationship is exponential. In contrast, the parameterized convection in the 15-km run is overly sensitive to convective inhibition and not sensitive enough to environmental moisture. The implications of these results on CCKW theories are discussed.
Origins of the Excessive Westward Extension of ENSO SST Simulated in CMIP5 and CMIP6 Models
Authors: Jiang Wenping , Huang Ping , Huang Gang , Ying Jun 
Published: January 2021

AbstractAn excessive westward extension of the simulated ENSO-related sea surface temperature (ENSO SST) variability in the CMIP5 and CMIP6 models is the most apparent ENSO SST pattern bias and dominates the intermodel spread in ENSO SST variability among the models. The ENSO SST bias lowers the models’ skill in ENSO-related simulations and induces large intermodel uncertainty in ENSO-related projections. The present study investigates the origins of the excessive westward extension of ENSO SST in 25 CMIP5 and 25 CMIP6 models. Based on the intermodel spread of ENSO SST variability simulated in the 50 models, we reveal that this ENSO SST bias among the models largely depends on the simulated cold tongue strength in the equatorial western Pacific (EWP). Models simulating a stronger cold tongue tend to simulate a larger mean zonal SST gradient in the EWP and then a larger zonal advection feedback in the EWP, favoring a more westward extension of the ENSO SST pattern. In addition, with the overall improvement in the EWP cold tongue from CMIP5 to CMIP6, the excessive westward extension bias of ENSO SST in CMIP6 models is also reduced relative to those in CMIP5 models. The results suggest that the bias and intermodel disagreement in the mean-state SST have been improved, which improves ENSO simulation.
Near-Inertial Waves and Turbulence Driven by the Growth of Swell
Authors: Wagner Gregory L. , Chini Gregory P. , Ramadhan Ali , Gallet Basile , Ferrari Raffaele 
Published: January 2021

AbstractBetween 5% and 25% of the total momentum transferred between the atmosphere and ocean is transmitted via the growth of long surface gravity waves called “swell.” In this paper, we use large-eddy simulations to show that swell-transmitted momentum excites near-inertial waves and drives turbulent mixing that deepens a rotating, stratified, turbulent ocean surface boundary layer. We find that swell-transmitted currents are less effective at producing turbulence and mixing the boundary layer than currents driven by an effective surface stress. Overall, however, the differences between swell-driven and surface-stress-driven boundary layers are relatively minor. In consequence, our results corroborate assumptions made in Earth system models that neglect the vertical structure of swell-transmitted momentum fluxes and instead parameterize all air–sea momentum transfer processes with an effective surface stress.
A Bimodal Diagnostic Cloud Fraction Parameterization. Part I: Motivating Analysis and Scheme Description
Authors: Van Weverberg Kwinten , Morcrette Cyril J. , Boutle Ian , Furtado Kalli , Field Paul R. 
Published: January 2021

AbstractCloud fraction parameterizations are beneficial to regional, convection-permitting numerical weather prediction. For its operational regional midlatitude forecasts, the Met Office uses a diagnostic cloud fraction scheme that relies on a unimodal, symmetric subgrid saturation-departure distribution. This scheme has been shown before to underestimate cloud cover and hence an empirically based bias correction is used operationally to improve performance. This first of a series of two papers proposes a new diagnostic cloud scheme as a more physically based alternative to the operational bias correction. The new cloud scheme identifies entrainment zones associated with strong temperature inversions. For model grid boxes located in this entrainment zone, collocated moist and dry Gaussian modes are used to represent the subgrid conditions. The mean and width of the Gaussian modes, inferred from the turbulent characteristics, are then used to diagnose cloud water content and cloud fraction. It is shown that the new scheme diagnoses enhanced cloud cover for a given gridbox mean humidity, similar to the current operational approach. It does so, however, in a physically meaningful way. Using observed aircraft data and ground-based retrievals over the southern Great Plains in the United States, it is shown that the new scheme improves the relation between cloud fraction, relative humidity, and liquid water content. An emergent property of the scheme is its ability to infer skewed and bimodal distributions from the large-scale state that qualitatively compare well against observations. A detailed evaluation and resolution sensitivity study will follow in Part II.
Measuring Marginal Crime Concentration: A New Solution to an Old Problem
Authors: Chalfin Aaron , Kaplan Jacob , Cuellar Maria 
Published: January 2021

Objectives: In his 2014 Sutherland address to the American Society of Criminology, David Weisburd demonstrated that the share of crime that is accounted for by the most crime-ridden street segments is notably high and strikingly similar across cities, an empirical regularity referred to as the “law of crime concentration.” In the large literature that has since proliferated, there remains considerable debate as to how crime concentration should be measured empirically. We suggest a measure of crime concentration that is simple, accurate and easily interpreted. Methods: Using data from three of the largest cities in the United States, we compare observed crime concentration to a counterfactual distribution of crimes generated by randomizing crimes to street segments. We show that this method avoids a key pitfall that causes a popular method of measuring crime concentration to considerably overstate the degree of crime concentration in a city. Results: While crime is significantly concentrated in a statistical sense and while some crimes are substantively concentrated among hot spots, the precise relationship is considerably weaker than has been documented in the empirical literature. Conclusions: The method we propose is simple and easily interpretable and compliments recent advances which use the Gini coefficient to measure crime concentration.