bluuebunny/crossref_metadata_2025_split huggingface dataset:
Landscape of KRASG12C, Associated Genomic Alterations, and Interrelation With Immuno-Oncology Biomarkers in KRAS-Mutated Cancers
Authors: Salem Mohamed E. , El-Refai Sherif M. , Sha Wei , Puccini Alberto , Grothey Axel , George Thomas J. , Hwang Jimmy J. , O'Neil Bert , Barrett Alexander S. , Kadakia Kunal C. , Musselwhite Laura W. , Raghavan Derek , Van Cutsem Eric , Tabernero Josep , Tie Jeanne 
Published: March 2022

PURPOSE Promising single-agent activity from sotorasib and adagrasib in KRASG12C-mutant tumors has provided clinical evidence of effective KRAS signaling inhibition. However, comprehensive analysis of KRAS-variant prevalence, genomic alterations, and the relationship between KRAS and immuno-oncology biomarkers is lacking. MATERIALS AND METHODS Retrospective analysis of deidentified records from 79,004 patients with various cancers who underwent next-generation sequencing was performed. Fisher's exact test evaluated the association between cancer subtypes and KRAS variants. Logistic regression assessed KRASG12C comutations with other oncogenes and the association between KRAS variants and immuno-oncology biomarkers. RESULTS Of the 79,004 samples assessed, 13,758 (17.4%) harbored KRAS mutations, with 1,632 (11.9%) harboring KRASG12C and 12,126 (88.1%) harboring other KRAS variants ( KRASnon-G12C). Compared with KRASnon-G12C across all tumor subtypes, KRASG12C was more prevalent in females (56% v 51%, false discovery rate-adjusted P value [FDR- P] = .0006), current or prior smokers (85% v 56%, FDR- P < .0001), and patients age > 60 years (73% v 63%, FDR- P ≤ .0001). The most frequent KRAS variants across all subtypes were G12D (29.5%), G12V (23.0%), G12C (11.9%), G13D (6.5%), and G12R (6.2%). KRASG12C was most prevalent in patients with non–small-cell lung cancer (9%), appendiceal (3.9%), colorectal (3.2%), tumor of unknown origin (1.6%), small bowel (1.43%), and pancreatic (1.3%) cancers. Compared with KRASnon-G12C-mutated, KRASG12C-mutated tumors were significantly associated with tumor mutational burden-high status (17.9% v 8.4%, odds ratio [OR] = 2.38; FDR- P < .0001). KRASG12C-mutated tumors exhibited a distinct comutation profile from KRASnon-G12C-mutated tumors, including higher comutations of STK11 (20.59% v 5.95%, OR = 4.10; FDR- P < .01) and KEAP1 (15.38% v 4.61%, OR = 3.76; FDR- P < .01). CONCLUSION This study presents the first large-scale, pan-cancer genomic characterization of KRASG12C. The KRASG12C mutation was more prevalent in females and older patients and appeared to be associated with smoking status. KRASG12C tumors exhibited a distinct comutation profile and were associated with tumor mutational burden-high status.
Moral Distress and Moral Injury Among Attending Neurosurgeons: A National Survey
Authors: Mackel Charles E. , Alterman Ron L. , Buss Mary K. , Reynolds Renée M. , Fox W. Christopher , Spiotta Alejandro M. , Davis Roger B. , Stippler Martina 
Published: March 2022

BACKGROUND:
“Moral distress” describes the psychological strain a provider faces when unable to uphold professional values because of external constraints. Recurrent or intense moral distress risks moral injury, burnout, and physician attrition but has not been systematically studied among neurosurgeons.

OBJECTIVE:
To develop a unique instrument to test moral distress among neurosurgeons, evaluate the frequency and intensity of scenarios that may elicit moral distress and injury, and determine their impact on neurosurgical burnout and turnover.

METHODS:
An online survey investigating moral distress, burnout, and practice patterns was emailed to attending neurosurgeon members of the Congress of Neurological Surgeons. Moral distress was evaluated through a novel survey designed for neurosurgical practice.

RESULTS:
A total of 173 neurosurgeons completed the survey. Half of neurosurgeons (47.7%) reported significant moral distress within the past year. The most common cause was managing critical patients lacking a clear treatment plan; the most intense distress was pressure from patient families to perform futile surgery. Multivariable analysis identified burnout and performing ≥2 futile surgeries per year as predictors of distress (P < .001). Moral distress led 9.8% of neurosurgeons to leave a position and 26.6% to contemplate leaving. The novel moral distress survey demonstrated excellent internal consistency (Cronbach alpha = 0.89).

CONCLUSION:
We developed a reliable survey assessing neurosurgical moral distress. Nearly, half of neurosurgeons suffered moral distress within the past year, most intensely from external pressure to perform futile surgery. Moral distress correlated with burnout risk caused 10% of neurosurgeons to leave a position and a quarter to consider leaving.
When light meets biology – how the specimen affects quantitative microscopy
Authors: Reiche Michael A. , Aaron Jesse S. , Boehm Ulrike , DeSantis Michael C. , Hobson Chad M. , Khuon Satya , Lee Rachel M. , Chew Teng-Leong 
Published: March 2022

ABSTRACT
Fluorescence microscopy images should not be treated as perfect representations of biology. Many factors within the biospecimen itself can drastically affect quantitative microscopy data. Whereas some sample-specific considerations, such as photobleaching and autofluorescence, are more commonly discussed, a holistic discussion of sample-related issues (which includes less-routine topics such as quenching, scattering and biological anisotropy) is required to appropriately guide life scientists through the subtleties inherent to bioimaging. Here, we consider how the interplay between light and a sample can cause common experimental pitfalls and unanticipated errors when drawing biological conclusions. Although some of these discrepancies can be minimized or controlled for, others require more pragmatic considerations when interpreting image data. Ultimately, the power lies in the hands of the experimenter. The goal of this Review is therefore to survey how biological samples can skew quantification and interpretation of microscopy data. Furthermore, we offer a perspective on how to manage many of these potential pitfalls.
Parasitoid wasp venom manipulates host innate behavior via subtype-specific dopamine receptor activation
Authors: Nordio Stefania , Kaiser Maayan , Adams Michael E. , Libersat Frederic 
Published: March 2022

ABSTRACT
The subjugation strategy employed by the jewel wasp is unique in that it manipulates the behavior of its host, the American cockroach, rather than inducing outright paralysis. Upon envenomation directly into the central complex (CX), a command center in the brain for motor behavior, the stung cockroach initially engages in intense grooming behavior, then falls into a lethargic sleep-like state referred to as hypokinesia. Behavioral changes evoked by the sting are due at least in part to the presence of the neurotransmitter dopamine in the venom. In insects, dopamine receptors are classified as two families, the D1-like and the D2-like receptors. However, specific roles played by dopamine receptor subtypes in venom-induced behavioral manipulation by the jewel wasp remain largely unknown. In the present study, we used a pharmacological approach to investigate roles of D1-like and D2-like receptors in behaviors exhibited by stung cockroaches, focusing on grooming. Specifically, we assessed behavioral outcomes of focal CX injections of dopamine receptor agonists and antagonists. Both specific and non-specific compounds were used. Our results strongly implicate D1-like dopamine receptors in venom-induced grooming. Regarding induction of hypokinesia, our findings demonstrate that dopamine signaling is necessary for induction of long-lasting hypokinesia caused by brain envenomation.
Two stressors are worse than one: combined heatwave and drought affect hydration state and glucocorticoid levels in a temperate ectotherm
Authors: Dezetter Mathias , Le Galliard Jean-François , Leroux-Coyau Mathieu , Brischoux François , Angelier Fréderic , Lourdais Olivier 
Published: March 2022

ABSTRACT
Heatwaves and droughts are becoming more intense and frequent with climate change. These extreme weather events often occur simultaneously and may alter organismal physiology, yet their combined impacts remain largely unknown. Here, we experimentally investigated physiological responses of a temperate ectotherm, the asp viper (Vipera aspis), to a simulated heatwave and drought. We applied a two-by-two factorial design by manipulating the daily temperature cycle (control versus heatwave) and the water availability (water available versus water deprived) over a month followed by exposure to standard thermal conditions with ad libitum access to water. Simulated heatwave and water deprivation additively increased mass loss, while water deprivation led to greater plasma osmolality (dehydration). Mass gain from drinking after the treatment period was higher in vipers from the heatwave and water-deprived group, suggesting that thirst was synergistically influenced by thermal and water constraints. Heatwave conditions and water deprivation also additively increased baseline corticosterone levels but did not influence basal metabolic rate and plasma markers of oxidative stress. Our results demonstrate that a short-term exposure to combined heatwave and drought can exacerbate physiological stress through additive effects, and interactively impact behavioral responses to dehydration. Considering combined effects of temperature and water availability is thus crucial to assess organismal responses to climate change.
A hyperpolarizing rod bipolar cell in the sea lamprey, Petromyzon marinus
Authors: Frederiksen Rikard , Fain Gordon L. , Sampath Alapakkam P. 
Published: March 2022

ABSTRACT
Retinal bipolar cells receive direct input from rod and cone photoreceptors and send axons into the inner retina, synapsing onto amacrine and ganglion cells. Bipolar cell responses can be either depolarizing (ON) or hyperpolarizing (OFF); in lower vertebrates, bipolar cells receive mixed rod and cone input, whereas in mammals, input is mostly segregated into 14 classes of cone ON and OFF cells and a single rod ON bipolar cell. We show that lamprey, like mammals, have rod bipolar cells with little or no cone input, but these cells are OFF rather than ON. They have a characteristic morphology and a spectral sensitivity nearly indistinguishable from that of rod photoreceptors. In background light known to saturate rods, rod bipolar cells are also saturated and cannot respond to increment flashes. Our results suggest that early vertebrate progenitors of both agnathans and gnathostomes may have had a more fluid retinal organization than previously thought.
An effective solution to boost generation from waves: Benefits of a hybrid energy storage system integration to wave energy converter in grid-connected systems
Authors: Barelli Linda , Bidini Gianni , Ciupageanu Dana Alexandra , Ottaviano Andrea , Pelosi Dario , Gallorini Federico , Alessandri Giacomo , Atcheson Cruz Mairead 
Published: March 2022

Background: Wave energy represents one of the most promising renewable energies due to its great theoretical potential. Nevertheless, the electrical compliance of grid-connected systems is a great issue nowadays, due to the highly stochastic nature of wave energy. Methods: In this paper, a Hybrid Energy Storage System (HESS) consisting of a Li-ion battery and a flywheel is coupled to a Wave Energy Converter (WEC) that operates in grid connected mode. The study is performed using real yearly wave power profiles relating to three different sites located along the European coasts. The Simultaneous Perturbation Stochastic Approximation (SPSA) principle is implemented as real-time power management strategy for HESS in wave energy conversion systems. Results: Obtained results demonstrate how the proposed HESS and the implementation of the SPSA power management coupled to a WEC allow a reduction of more than 80% of power oscillations at the Point of Common Coupling (PCC), while proving the robustness of the developed management strategy over the investigated sites. Moreover, the average energy penalty due to the HESS integration results slightly higher than 5% and battery solicitation is reduced by more than 64% with respect to the flywheel solicitation, contributing to extend its lifetime. Conclusions: HESS integration in renewable generation systems maximizes the WEC production while smoothing the power at the PCC. Specifically, flywheel-battery HESS together with the implemented power management strategy could provide a great flexibility in the view of increasing power production from waves, strongly mitigating the variability of this source while enhancing grid safety and stability.
Psychological specificity of the representation of vandalism of traffic signs in Russian megalopolises
Authors: Kruzhkova Ol'ga , Vorob'eva Irina 
Published: March 2022

Vandalism of traffic signs is a phenomenon that arose in the 20th century and is not only in the stage of its formation, but also has no comprehensive scientific justification today, both from the standpoint of the determinants of occurrence, and from the point of view of its likely consequences for society. Vandal damage of traffic signs is varied – from tagging and sticking with stickers, to deformation of the sign or its dismantling and theft.
At the same time, in the works of researchers, a decrease in the ability of a vandal-damaged sign to effectively regulate traffic is noted, which can lead to potentially dangerous situations on the road. Despite the significance of the problem, empirical studies of vandalism of traffic signs were carried out mainly in the United States, the experience of which cannot be extrapolated to Russian reality due to cultural, economic and social reasons. Thus, the purpose of the study presented in the article was to identify the specifics of vandalism of traffic signs in the conditions of Russian megalopolises.
In the period of 2021, empirical material was collected using the method of photographing vandally damaged traffic signs in three megalopolises of the Russian Federation (Vladivostok, Ekaterinburg, St. Petersburg), carried out as part of the route photographing of vandal transformations of the urban environment. For the analysis, 63 images of vandal-damaged traffic signs were selected, which were later evaluated by experts. It was found that the most frequently vandalized information signs and signs of additional information, which have a white background and a rectangular shape, acting as an actual "canvas" for vandals. Tagging and pasting with stickers (70.4% and 59.2% of cases of vandal damaged signs, respectively) become typical damage to signs.
The study of vandalism of traffic signs, its causes, the degree of threat to road safety, the possibility of preventing illegitimate transformations requires additional research, which is especially relevant with the growing trend towards vandal transformation of road signs in the modern conditions of Russian megalopolises.
The study was supported by a grant from the Russian Science Foundation (project no. 17-18-01278).
The image of an ideal marriage for men and women
Authors: Mikhaylov Aleksey , Sobolev Nikolay , Emel'yanova Elena , Nesterov Vladimir , Ershova Nina , Fel'can Yuliya 
Published: March 2022

Every day a person is faced with a large number of tasks, the outcome of which involves the adoption of one or another decision: simple or complex. And one day each of us is faced with a choice on which our whole future life depends - this is the choice of a "second half", a partner for further life together. This issue should be approached very thoroughly and seriously for both a woman and a man, because when creating a family, young people take on a great responsibility, which lies in the fact that they create, first of all, a “socialization institution” for their future children. Consequently, their future depends on the quality and reliability of the created family.
Methodological basis of the research: theoretical and empirical development of the problem of ideas about marriage and attitudes towards marriage A. A. Rean, L. V. Kartseva, M. S. Krasnokutskaya, N. G. Lagoyda.
Methodical research apparatus:
1. Psychodiagnostic methods: the method of unfinished sentences and the method of questioning.
2. Methods of mathematical data processing: U - Mann-Whitney criterion. Data processing was carried out on the basis of the SPSS computer program.
Theoretical significance of the study: at present, there is no unambiguous understanding of the ideal marriage in scientific research. The conducted research will contribute to the generalization of the available theoretical knowledge in this area.
Practical significance of the study: The data obtained will be useful to specialists who advise young people on marriage.
Empirical study base: Conducted in November 2019. The respondents were students of 1-4 courses of various educational institutions of the city of Kirov (N = 87) aged 17 to 23 years, including 34 boys and 53 girls.
A Restricted Dual Peaceman-Rachford Splitting Method for a Strengthened DNN Relaxation for QAP
Authors: Graham Naomi , Hu Hao , Im Jiyoung , Li Xinxin , Wolkowicz Henry 
Published: March 2022

Splitting methods in optimization arise when one can divide an optimization problem into two or more simpler subproblems. They have proven particularly successful for relaxations of problems involving discrete variables. We revisit and strengthen splitting methods for solving doubly nonnegative relaxations of the particularly difficult, NP-hard quadratic assignment problem. We use a modified restricted contractive splitting method approach. In particular, we show how to exploit redundant constraints in the subproblems. Our strengthened bounds exploit these new subproblems and new dual multiplier estimates to improve on the bounds and convergence results in the literature. Summary of Contribution: In our paper, we consider the quadratic assignment problem (QAP). It is one of the fundamental combinatorial optimization problems in the fields of optimization and operations research and includes many fundamental applications. We revisit and strengthen splitting methods for solving doubly nonnegative (DNN) relaxation of the QAP. We use a modified restricted contractive splitting method. We obtain strengthened bounds from improved lower and upper bounding techniques, and in fact, we solve many of these NP-hard problems to (provable) optimality, thus illustrating both the strength of the DNN relaxation and our new bounding techniques.
Public perceptions of the veterinary nurse
Authors: McCormick Kelsey Elizabeth Ann 
Published: March 2022

Background: The veterinary nursing profession has undergone major developments since its formation, with veterinary nurses (VN) becoming registered professionals in their own right. Despite this, there is still a lack of public recognition of and respect for the VN role. Currently, there are limited data on public perceptions and opinions of the VN. Aims: The purpose of this study was to determine the public's perceptions and awareness of the VN's role. Methods: Members of the public answered an online questionnaire about their experience and opinion of VNs. Results: A total of 148 valid responses were received. Results showed 90.5% of respondents had a positive opinion of VNs, and 98.6% believed the VN's role was important. Unsure opinions of the VN were a result of a lack of interaction and understanding of the VN's role. Conclusion: Social media may play an instrumental role in increasing public awareness and recognition of the VN's highly skilled role. Further research is required to accurately determine the general public's perception of the VN.
Efficacy and safety of antimicrobial stewardship prospective audit and feedback in patients hospitalized with COVID-19: A protocol for a pragmatic clinical trial
Authors: Chen Justin Z. , Hoang Holly L. , Yaskina Maryna , Kabbani Dima , Doucette Karen E. , Smith Stephanie W. , Lau Cecilia , Stewart Jackson , Zurek Karen , Schultz Morgan , Cervera Carlos 
Published: March 2022

Background
The use of broad-spectrum antibiotics is widespread in patients with COVID-19 despite a low prevalence of bacterial co-infection, raising concerns for the accelerated development of antimicrobial resistance. Antimicrobial stewardship (AMS) is vital but there are limited randomized clinical trial data supporting AMS interventions such as prospective audit and feedback (PAF). High quality data to demonstrate safety and efficacy of AMS PAF in hospitalized COVID-19 patients are needed.

Methods and design
This is a prospective, multi-center, non-inferiority, pragmatic randomized clinical trial evaluating AMS PAF intervention plus standard of care (SOC) versus SOC alone. We include patients with microbiologically confirmed SARS-CoV-2 infection requiring hospital admission for severe COVID-19 pneumonia. Eligible ward beds and critical care unit beds will be randomized prior to study commencement at each participating site by computer-generated allocation sequence stratified by intensive care unit versus conventional ward in a 1:1 fashion. PAF intervention consists of real time review of antibacterial prescriptions and immediate written and verbal feedback to attending teams, performed by site-based AMS teams comprised of an AMS pharmacist and physician. The primary outcome is clinical status at post-admission day 15 measured using a 7-point ordinal scale. Patients will be followed for secondary outcomes out to 30 days. A total of 530 patients are needed to show a statistically significant non-inferiority, with 80% power and 2.5% one-sided alpha assuming standard deviation of 2 and the non-inferiority margin of 0.5.

Discussion
This study protocol presents a pragmatic clinical trial design with small unit cluster randomization for AMS intervention in hospitalized COVID-19 that will provide high-level evidence and may be adopted in other clinical situations.

Trial registration
This study is being performed at the University of Alberta and is registered at ClinicalTrials.gov (NCT04896866) on May 17, 2021.