bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychotropic and pain medication use in individuals with traumatic brain injury—a Swedish total population cohort study of 240 000 persons
Authors: Molero Yasmina , Sharp David James , D'Onofrio Brian Matthew , Larsson Henrik , Fazel Seena 
Published: February 2021

ObjectiveTo examine psychotropic and pain medication use in a population-based cohort of individuals with traumatic brain injury (TBI), and compare them with controls from similar backgrounds.MethodsWe assessed Swedish nationwide registers to include all individuals diagnosed with incident TBI between 2006 and 2012 in hospitals or specialist outpatient care. Full siblings never diagnosed with TBI acted as controls. We examined dispensed prescriptions for psychotropic and pain medications for the 12 months before and after the TBI.ResultsWe identified 239 425 individuals with incident TBI, and 199 658 unaffected sibling controls. In the TBI cohort, 36.6% had collected at least one prescription for a psychotropic or pain medication in the 12 months before the TBI. In the 12 months after, medication use increased to 45.0%, an absolute rate increase of 8.4% (p<0.001). The largest post-TBI increases were found for opioids (from 16.3% to 21.6%, p<0.001), and non-opioid pain medications (from 20.3% to 26.6%, p<0.001). The majority of prescriptions were short-term; 20.6% of those prescribed opioids and 37.3% of those with benzodiazepines collected prescriptions for more than 6 months. Increased odds of any psychotropic or pain medication were associated with individuals before (OR: 1.62, 95% CI: 1.59 to 1.65), and after the TBI (OR: 2.30, 95% CI: 2.26 to 2.34) as compared with sibling controls, and ORs were consistently increased for all medication classes.ConclusionHigh rates of psychotropic and pain medications after a TBI suggest that medical follow-up should be routine and review medication use.
Cognitive reserve in amyotrophic lateral sclerosis (ALS): a population-based longitudinal study
Authors: Costello Emmet , Rooney James , Pinto-Grau Marta , Burke Tom , Elamin Marwa , Bede Peter , McMackin Roisin , Dukic Stefan , Vajda Alice , Heverin Mark , Hardiman Orla , Pender Niall 
Published: February 2021

BackgroundAmyotrophic lateral sclerosis (ALS) is often associated with cognitive and/or behavioural impairment. Cognitive reserve (CR) may play a protective role in offsetting cognitive impairment. This study examined the relationship between CR and longitudinal change in cognition in an Irish ALS cohort.MethodsLongitudinal neuropsychological assessment was carried out on 189 patients over 16 months using the Edinburgh cognitive and behavioural ALS screen (ECAS) and an additional battery of neuropsychological tests. CR was measured by combining education, occupation and physical activity data. Joint longitudinal and time-to-event models were fitted to investigate the associations between CR, performance at baseline and decline over time while controlling for non-random drop-out.ResultsCR was a significant predictor of baseline neuropsychological performance, with high CR patients performing better than those with medium or low CR. Better cognitive performance in high CR individuals was maintained longitudinally for ECAS, social cognition, executive functioning and confrontational naming. Patients displayed little cognitive decline over the course of the study, despite controlling for non-random drop-out.ConclusionsThese findings suggest that CR plays a role in the presentation of cognitive impairment at diagnosis but is not protective against cognitive decline. However, further research is needed to examine the interaction between CR and other objective correlates of cognitive impairment in ALS.
Risk factors for cognitive impairment in amyotrophic lateral sclerosis: a systematic review and meta-analysis
Authors: Yang Tianmi , Hou Yanbing , Li Chunyu , Cao Bei , Cheng Yangfan , Wei Qianqian , Zhang Lingyu , Shang Huifang 
Published: February 2021

ObjectiveCognitive impairment is a common, far-reaching but imperceptible manifestation in patients with amyotrophic lateral sclerosis (ALS). We aimed to identify the risk factors for cognitive impairment in ALS.MethodsWe searched PubMed and EMBASE for cross-sectional, case–control and cohort studies that reported predictors of cognitive impairment in ALS. The obtained data were meta-analysed to generate overall ORs and 95% CIs.ResultsTwenty-seven eligible articles reporting on 6799 individuals were included out of 20 501 records. Nine predictors were identified: C9orf72 (OR 3.62, 95% CI 1.76 to 7.45), dysarthria (OR 2.25, 95% CI 1.20 to 4.22), family history of ALS (OR 1.76, 95% CI 1.18 to 2.61), predominant upper motor neuron (PUMN) phenotype (OR 1.73, 95% CI 1.09 to 2.73) and bulbar onset (OR 1.54, 95% CI 1.28 to 1.87) increased risk factors for cognitive impairment in ALS. ALS Functional Rating Scale-Revised scores, sex, age or education level were not significantly associated with cognitive impairment in ALS. In addition, C9orf72 (OR=5.94) and bulbar onset (OR=2.08) were strong predictors of ALS-frontotemporal dementia. Female sex conferred more susceptibility to executive cognitive impairment than male sex (OR=1.82).ConclusionsPatients with C9orf72 repeat expansion, dysarthria, family history of ALS, PUMN phenotype and bulbar onset had a high risk for cognitive impairment in ALS. These associations may contribute to understanding the heterogeneity of ALS.PROSPERO registration numberCRD42020201085.
Effect of sodium-glucose cotransporter-2 inhibitors on renal handling of electrolytes
Authors: Meena Priti , Bhargava Vinant , Bhalla Anil , Rana Devinder , Mantri Alok 
Published: February 2021

ABSTRACTSodium-glucose cotransporter-2 inhibitors (SGLT2i) are the latest introduction into the armamentarium of diabetes care in the present decade. By virtue of their beneficial effects, such as blood pressure-lowering, bodyweight reduction and significant renal and cardioprotective effects which extends beyond their glycaemic control effects, SGLT2i have become one of the most preferred oral antihyperglycaemic agents of recent times. However, they can influence tubular handling of electrolytes that can result in some electrolyte disturbances such as alteration in the serum levels of magnesium, potassium and phosphate levels. Some of these changes are mild or transient and may not have significant clinical implications. The underlying putative mechanism(s) responsible for disturbances of electrolytes are yet to be deciphered. In this review, we aim to describe electrolytes and acid–base abnormalities due to SGLT2i as well as to elucidate the underlying mechanism.
What do beta-lactams add to vancomycin or daptomycin in the treatment of patients with methicillin-resistantStaphylococcus aureusbacteraemia? A review
Authors: García Aragonés Laura , Blanch Sancho José Javier , Segura Luque Juan Carlos , Mateos Rodriguez Fernando , Martínez Alfaro Elisa , Solís García del Pozo Julián 
Published: February 2021

AbstractSeveral studies have documented the synergy between vancomycin/daptomycin and various beta-lactams, and clinical studies have studied this combination therapy in humans. We review the published literature on this topic to know the utility of the combined treatment with beta-lactams in treating bacteraemia methicillin-resistant Staphylococcus aureus (MRSA) infections. Fifteen observational studies, three randomised clinical trials and three systematics reviews are analysed in this article. Observational studies used ceftaroline, cefazolin, piperacillin/tazobactam or cefepime among the beta-lactams. Clinical trials used cloxacillin or flucloxacillin as the most used beta-lactam in two trials and ceftaroline in one. Three systematic reviews are published. One of them only includes studies with vancomycin and included six studies. The other two systematic reviews include patients with daptomycin or vancomycin and included 15 and 9 studies, respectively. Adding a beta-lactam to vancomycin or daptomycin may help shorten bacteraemia and avoid recurrences in patients with MRSA bacteraemia. There is no evidence that combined therapy improves mortality. Nephrotoxicity in clinical trials precludes the use of combination therapy mainly with cloxacillin or flucloxacillin, but systematic reviews have not found a significant difference in this point in observational studies with other beta-lactams. The role of other beta-lactams such as ceftaroline should be thoroughly studied in these patients.
Guidance for providing effective feedback in clinical supervision in postgraduate medical education: a systematic review
Authors: Weallans Jessica , Roberts Caroline , Hamilton Sarah , Parker Stephen 
Published: February 2021

AbstractThe primary aim was to systematically review the empirical evidence relating to models and guidance for providing effective feedback in clinical supervision occurring in postgraduate medical education contexts. A secondary aim was to identify the common and differentiating components of models and guidance for providing effective feedback in this context. A systematic review was conducted. Fifty-one records met the inclusion criteria, including 12 empirical studies. Empirical records meeting inclusion criteria were critically appraised. Qualitative content analysis was applied to the guidance on effective and ineffective feedback provision to identify key principles. A composite model was created synthesising the guidance identified for providing effective feedback. The evidence supporting specific models and guidance in postgraduate medical education was limited. However, there is evidence to support all of the commonly identified principles. In addition, a consensus about the principles of effective feedback in clinical supervision in postgraduate medical education was found.
Viscous properties of hot and dense QCD matter in the presence of a magnetic field
Authors: Rath Shubhalaxmi , Patra Binoy Krishna 
Published: February 2021

AbstractWe have studied the effect of strong magnetic field on the viscous properties of hot QCD matter at finite chemical potential by calculating the shear viscosity ($$\eta $$
η
) and the bulk viscosity ($$\zeta $$
ζ
). The viscosities have been calculated using the relativistic Boltzmann transport equation within the relaxation time approximation. The interactions among partons are incorporated through their quasiparticle masses at finite temperature, strong magnetic field and finite chemical potential. From this study, one can understand the influence of strong magnetic field and the influence of chemical potential on the sound attenuation through the Prandtl number (Pl), on the nature of the flow by the Reynolds number (Rl), and on the relative behavior between the shear viscosity and the bulk viscosity through the ratio $$\zeta /\eta $$

ζ
/
η

. We have observed that, both shear and bulk viscosities get increased in the presence of a strong magnetic field and the additional presence of chemical potential further enhances their magnitudes. With the increase of temperature, $$\eta $$
η
increases for the medium in the presence of a strong magnetic field as well as for the isotropic medium in the absence of magnetic field, whereas $$\zeta $$
ζ
is found to decrease with the temperature, contrary to its increase in the absence of magnetic field. We have observed that, the Prandtl number gets increased in the presence of strong magnetic field and finite chemical potential as compared to that in the isotropic medium, but it always remains larger than unity, thus instead of the thermal diffusion, the momentum diffusion largely affects the sound attenuation in the medium and this is more vigorous in the presence of both strong magnetic field and finite chemical potential. However, the Reynolds number becomes lowered than unity in an ambience of strong magnetic field and even gets further decreased in an additional presence of chemical potential, thus it implies the dominance of kinematic viscosity over the characteristic length scale of the system. Finally, the ratio $$\zeta /\eta $$

ζ
/
η

is amplified to the value larger than unity, contrary to its value in the absence of magnetic field and chemical potential where it is less than unity, thus it is inferred that the bulk viscosity prevails over the shear viscosity for the hot and dense QCD matter in the presence of a strong magnetic field.
Robustly Safe Compilation, an Efficient Form of Secure Compilation
Authors: Patrignani Marco , Garg Deepak 
Published: February 2021

Security-preserving compilers generate compiled code that withstands target-level attacks such as alteration of control flow, data leaks, or memory corruption. Many existing security-preserving compilers are proven to be fully abstract, meaning that they reflect and preserve observational equivalence. Fully abstract compilation is strong and useful but, in certain cases, comes at the cost of requiring expensive runtime constructs in compiled code. These constructs may have no relevance for security, but are needed to accommodate differences between the source and target languages that fully abstract compilation necessarily needs.

As an alternative to fully abstract compilation, this article explores a different criterion for secure compilation called robustly safe compilation or
RSC
. Briefly, this criterion means that the compiled code preserves relevant safety properties of the source program against all adversarial contexts interacting with the compiled program. We show that
RSC
can be proved more easily than fully abstract compilation and also often results in more efficient code. We also present two different proof techniques for establishing that a compiler attains
RSC
and, to illustrate them, develop three illustrative robustly safe compilers that rely on different target-level protection mechanisms. We then proceed to turn one of our compilers into a fully abstract one and through this example argue that proving
RSC
can be simpler than proving full abstraction.

To better explain and clarify notions, this article uses syntax highlighting in a way that colourblind and black-8-white readers can benefit from Reference [58]. For a better experience, please print or view this article in colour
.
1
Cryptographic Software IP Protection without Compromising Performance or Timing Side-channel Leakage
Authors: Biswas Arnab Kumar 
Published: February 2021

Program obfuscation is a widely used cryptographic software intellectual property (IP) protection technique against reverse engineering attacks in embedded systems. However, very few works have studied the impact of combining various obfuscation techniques on the obscurity (difficulty of reverse engineering) and performance (execution time) of obfuscated programs. In this article, we propose a Genetic Algorithm (GA)-based framework that not only optimizes obscurity and performance of obfuscated cryptographic programs, but it also ensures very low timing side-channel leakage. Our proposed
T
iming
S
ide
C
hannel
S
ensitive
P
rogram
O
bfuscation
O
ptimization
F
ramework (TSC-SPOOF) determines the combination of obfuscation transformation functions that produce optimized obfuscated programs with preferred optimization parameters. In particular, TSC-SPOOF employs normalized compression distance (NCD) and channel capacity to measure obscurity and timing side-channel leakage, respectively. We also use RISC-V rocket core running on a Xilinx Zynq FPGA device as part of our framework to obtain realistic results. The experimental results clearly show that our proposed solution leads to cryptographic programs with lower execution time, higher obscurity, and lower timing side-channel leakage than unguided obfuscation.
Safety and Clinical Activity of Atezolizumab in Patients with Metastatic Castration-Resistant Prostate Cancer: A Phase I Study
Authors: Petrylak Daniel P. , Loriot Yohann , Shaffer David R. , Braiteh Fadi , Powderly John , Harshman Lauren C. , Conkling Paul , Delord Jean-Pierre , Gordon Michael , Kim Joseph W. , Sarkar Indrani , Yuen Kobe , Kadel Edward E. , Mariathasan Sanjeev , O'Hear Carol , Narayanan Sujata , Fassò Marcella , Carroll Susheela , Powles Thomas 
Published: February 2021

Abstract

Purpose:
Atezolizumab [anti–programmed death-ligand 1 (anti-PD-L1)] is well tolerated and efficacious in multiple cancers, but has not been previously evaluated in metastatic castration-resistant prostate cancer (mCRPC). This study examined the safety, efficacy, and biomarkers of atezolizumab monotherapy for mCRPC.

Patients and Methods:
This phase Ia, open-label, dose-escalation and dose-expansion study (PCD4989g) enrolled patients with mCRPC who had progressed on sipuleucel-T or enzalutamide. Atezolizumab was given intravenously every 3 weeks until confirmed disease progression or loss of clinical benefit. Prespecified endpoints included safety, efficacy, biomarker analyses, and radiographic assessments.

Results:
All 35 evaluable patients [median age, 68 years (range, 45–83 years)] received atezolizumab after ≥1 prior line of therapy; 62.9% of patients had received ≥3 prior lines. Treatment-related adverse events occurred in 21 patients (60.0%), with no deaths. One patient had a confirmed partial response (PR) per RECIST 1.1, and 1 patient had a PR per immune-related response criteria. The confirmed 50% PSA response rate was 8.6% (3 patients). Median overall survival (OS) was 14.7 months [95% confidence interval (CI): 5.9–not evaluable], with a 1-year OS rate of 52.3% (95% CI: 34–70); 2-year OS was 35.9% (95% CI: 13–59). Median follow-up was 13.0 months (range, 1.2–28.1 months). Biomarker analyses showed that atezolizumab activated immune responses; however, a composite biomarker failed to reveal consistent correlations with efficacy.

Conclusions:
Atezolizumab was generally well tolerated in patients with mCRPC, with a safety profile consistent with other tumor types. In heavily pretreated patients, atezolizumab monotherapy demonstrated evidence of disease control; however, its limited efficacy suggests a combination approach may be needed.
Synthetic Lethal Screens Reveal Cotargeting FAK and MEK as a Multimodal Precision Therapy forGNAQ-Driven Uveal Melanoma
Authors: Paradis Justine S. , Acosta Monica , Saddawi-Konefka Robert , Kishore Ayush , Lubrano Simone , Gomes Frederico , Arang Nadia , Tiago Manoela , Coma Silvia , Wu Xingyu , Ford Kyle , Day Chi-Ping , Merlino Glenn , Mali Prashant , Pachter Jonathan A. , Sato Takami , Aplin Andrew E. , Gutkind J. Silvio 
Published: February 2021

AbstractPurpose:Uveal melanoma is the most common eye cancer in adults. Approximately 50% of patients with uveal melanoma develop metastatic uveal melanoma (mUM) in the liver, even after successful treatment of the primary lesions. mUM is refractory to current chemo- and immune-therapies, and most mUM patients die within a year. Uveal melanoma is characterized by gain-of-function mutations in GNAQ/GNA11, encoding Gαq proteins. We have recently shown that the Gαq–oncogenic signaling circuitry involves a noncanonical pathway distinct from the classical activation of PLCβ and MEK–ERK. GNAQ promotes the activation of YAP1, a key oncogenic driver, through focal adhesion kinase (FAK), thereby identifying FAK as a druggable signaling hub downstream from GNAQ. However, targeted therapies often activate compensatory resistance mechanisms leading to cancer relapse and treatment failure.Experimental Design:We performed a kinome-wide CRISPR-Cas9 sgRNA screen to identify synthetic lethal gene interactions that can be exploited therapeutically. Candidate adaptive resistance mechanisms were investigated by cotargeting strategies in uveal melanoma and mUM in vitro and in vivo experimental systems.Results:sgRNAs targeting the PKC and MEK–ERK signaling pathways were significantly depleted after FAK inhibition, with ERK activation representing a predominant resistance mechanism. Pharmacologic inhibition of MEK and FAK showed remarkable synergistic growth-inhibitory effects in uveal melanoma cells and exerted cytotoxic effects, leading to tumor collapse in uveal melanoma xenograft and liver mUM models in vivo.Conclusions:Coupling the unique genetic landscape of uveal melanoma with the power of unbiased genetic screens, our studies reveal that FAK and MEK–ERK cotargeting may provide a new network-based precision therapeutic strategy for mUM treatment.See related commentary by Harbour, p. 2967
Activity of Crizotinib in Patients with ALK-Aberrant Relapsed/Refractory Neuroblastoma: A Children's Oncology Group Study (ADVL0912)
Authors: Foster Jennifer H. , Voss Stephan D. , Hall David C. , Minard Charles G. , Balis Frank M. , Wilner Keith , Berg Stacey L. , Fox Elizabeth , Adamson Peter C. , Blaney Susan M. , Weigel Brenda J. , Mossé Yael P. 
Published: February 2021

Abstract

Purpose:
Anaplastic lymphoma kinase (ALK) aberrations are a promising target for patients with neuroblastoma. We assessed the activity of first-generation ALK inhibitor crizotinib in patients with no known curative treatments and whose tumors harbored an activating ALK alteration.

Patients and Methods:
Twenty patients with relapsed/refractory ALK-positive neuroblastoma received crizotinib at the recommended phase II dose of 280 mg/m2/dose. A Simon two-stage design was used to evaluate the antitumor activity of crizotinib monotherapy. Response evaluation occurred after cycles 1, 3, 5, 7, and then every 3 cycles. Correlation of ALK status and response was a secondary aim of the study.

Results:
The objective response rate for patients with neuroblastoma was 15% [95% confidence interval (CI): 3.3%–34.3%]: two with partial responses and 1 with a complete response. All three patients had a somatic ALK Arg1275Gln mutation, the most common ALK hotspot mutation observed in neuroblastoma and the only mutation predicted to be sensitive to ALK inhibition with crizotinib. Two patients had prolonged stable disease (10 and 13 cycles, respectively); both harbored an ALK Arg1275Gln mutation. Three patients with ALK Phe1174Leu mutations progressed during cycle 1 of therapy, and one patient with an ALK Phe1174Val received three cycles before disease progression. The two patients with ALK amplification had no response. The most common adverse event was a decrease in neutrophil count.

Conclusions:
Despite limited activity seen in this trial, we conclude that this is more likely due to an inability to reach the higher concentrations of crizotinib needed to overcome the competing ATP affinity.
See related commentary by Schulte and Eggert, p. 3507
Implementation of Human Robot Interaction on UDOO Board
Authors: Nepali Min Raj , Karthik Priyanka C , Majumdar Jharna 
Published: February 2021

<p>Advanced Robot for Interactive Application (ARIA) is a Humanoid Robotic Head which is capable of mimicking Various Human Facial Expressions. Much work has been done on Implementation of Humanoid Robotic Head with High end systems and Personal Computers (PCs). This paper presents the essential elements necessary for the implementation of Advanced Robot for Interactive Application (ARIA) on UDOO Board. The main aim of the Project was to develop a control system and Graphical User Interface (GUI) for ARIA to deliver real time human facial expressions using embedded board. Humanoid Robotic Head which is capable of mimicking Human Facial Expressions in Real time. Implementation of ARIA involved careful selection of Embedded Board, actuators, control algorithms, motor drivers, operating system, communication protocols, and programming languages. The Board contains a Quad Core A9 Processor and a Controller embedded on it, which are interconnected. In this project the controller is dedicated to control micro servo motors which are controlling eyes, eyebrows and eyelids movements whereas the Processor Handles the Dynamixel motors, GUI and different communication modules.</p>