bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fragment-based discovery of a new class of inhibitors targeting mycobacterial tRNA modification
Authors: Thomas Sherine E , Whitehouse Andrew J , Brown Karen , Burbaud Sophie , Belardinelli Juan M , Sangen Jasper , Lahiri Ramanuj , Libardo Mark Daben J , Gupta Pooja , Malhotra Sony , Boshoff Helena I M , Jackson Mary , Abell Chris , Coyne Anthony G , Blundell Tom L , Floto Rodrigo Andres , Mendes Vítor 
Published: June 2020

Abstract
Translational frameshift errors are often deleterious to the synthesis of functional proteins and could therefore be promoted therapeutically to kill bacteria. TrmD (tRNA-(N(1)G37) methyltransferase) is an essential tRNA modification enzyme in bacteria that prevents +1 errors in the reading frame during protein translation and represents an attractive potential target for the development of new antibiotics. Here, we describe the application of a structure-guided fragment-based drug discovery approach to the design of a new class of inhibitors against TrmD in Mycobacterium abscessus. Fragment library screening, followed by structure-guided chemical elaboration of hits, led to the rapid development of drug-like molecules with potent in vitro TrmD inhibitory activity. Several of these compounds exhibit activity against planktonic M. abscessus and M. tuberculosis as well as against intracellular M. abscessus and M. leprae, indicating their potential as the basis for a novel class of broad-spectrum mycobacterial drugs.
Altering the rate-determining step over cobalt single clusters leading to highly efficient ammonia synthesis
Authors: Liu Sisi , Wang Mengfan , Ji Haoqing , Shen Xiaowei , Yan Chenglin , Qian Tao 
Published: June 2020

Abstract
Activation of high-energy triple-bonds of N2 is the most significant bottleneck of ammonia synthesis under ambient conditions. Here, by importing cobalt single clusters as strong electron-donating promoter into the catalyst, the rate-determining step of ammonia synthesis is altered to the subsequent proton addition so that the barrier of N2 dissociation can be successfully overcome. As revealed by density functional theory calculations, the N2 dissociation becomes exothermic over the cobalt single cluster upon the strong electron backdonation from metal to the N2 antibonding orbitals. The energy barrier of the positively shifted rate-determining step is also greatly reduced. At the same time, advanced sampling molecular dynamics simulations indicate a barrier-less process of the N2 approaching the active sites that greatly facilitates the mass transfer. With suitable thermodynamic and dynamic property, a high ammonia yield rate of 76.2 μg h–1 mg$^{-1 }_{\rm cat.}$ and superior Faradaic efficiency of 52.9% were simultaneously achieved.
Cannabis-impaired driving and Canadian youth
Authors: Brubacher Jeff R , Chan Herbert , Staples John A 
Published: June 2020

Abstract
Acute cannabis use results in inattention, delayed information processing, impaired coordination, and slowed reaction time. Driving simulator studies and epidemiologic analyses suggest that cannabis use increases motor vehicle crash risk. How much concern should we have regarding cannabis associated motor vehicle collision risks among younger drivers? This article summarizes why young, inexperienced drivers may be at a particularly high risk of crashing after using cannabis. We describe the epidemiology of cannabis use among younger drivers, why combining cannabis with alcohol causes significant impairment and why cannabis edibles may pose a heightened risk to traffic safety. We provide recommendations for clinicians counselling younger drivers about cannabis use and driving.
Counselling adolescents and parents about cannabis: A primer for health professionals
Authors: Bélanger Richard E , Grant Christina N 
Published: June 2020

Abstract
While cannabis use among adolescents is frequent in Canada, youth do recognize the potential harms, and increasingly expect knowledgeable health care providers to discuss substance use in everyday practice. This practice point provides sound, evidence-based tools to help health professionals address nonmedical (recreational) cannabis use and its related risks. After highlighting how to make the clinical setting a safe space for youth to talk about psychoactive substances, specific strategies for approaching cannabis use in effective, developmentally appropriate ways are described. Consistent with current literature, screening questionnaires to help structure discussion and identify adolescents who may benefit from more specialized interventions are recommended. Because one in six adolescents who experiments with cannabis goes on to misuse it, appraising their willingness to change risky behaviours is a key aspect of care, along with supportive goal-setting and helping families. Recommended resources for practitioners and parents are included.
Newborn white matter microstructure moderates the association between maternal postpartum depressive symptoms and infant negative reactivity
Authors: Nolvi Saara , Tuulari Jetro J , Lavonius Tuomas , Scheinin Noora M , Lehtola Satu J , Lavonius Maria , Merisaari Harri , Saunavaara Jani , Korja Riikka , Kataja Eeva-Leena , Pelto Juho , Parkkola Riitta , Karlsson Linnea , Karlsson Hasse 
Published: June 2020

AbstractMaternal postpartum depression is a prominent risk factor for aberrant child socioemotional development, but there is little understanding about the neural phenotypes that underlie infant sensitivity to maternal depression. We examined whether newborn white matter fractional anisotropy (FA), a measure of white matter maturity, moderates the association between maternal postpartum depressive symptoms and infant negative reactivity at 6 months. Participants were 80 mother–infant dyads participating in a prospective population-based cohort, and included families whose newborns underwent a magnetic resonance/diffusion tensor imaging scan at 2–5 weeks of age and whose mothers reported their own depressive symptoms at 3 and 6 months postpartum and infant negative emotional reactivity at 6 months. The whole-brain FA moderated the association between maternal depressive symptoms and mother-reported infant negative reactivity at 6 months after adjusting for the covariates. Maternal depressive symptoms were positively related to infant negative reactivity among infants with high or average FA in the whole brain and in corpus callosum and cingulum, but not among those with low FA. The link between maternal depressive symptoms and infant negative reactivity was moderated by newborn FA. The variation in white matter microstructure might play a role in child susceptibility to parental distress.
Broad Spectrum Treatment for Ocular Insult Induced by Organophosphate Chemical Warfare Agents
Authors: Gore Ariel 
Published: June 2020

Abstract
Warfare organophosphates nerve agents constitute one of the prime threats to mankind on the battlefield and in the scenario of civilian terror. Exposure to organophosphate (OP) nerve agents dose-dependently result in incapacitation. They affect multiple organs, but the eye is one of the first and most frequently affected. Ocular OP insult may result in long-term miosis, impaired visual function, and ocular pain thus inducing functional incapacitation. The currently recommended military medical doctrine of using 1% atropine eye drops is far from being the optimal treatment. Although effective in reducing ocular pain and the miotic response, this treatment induces long-term mydriasis and cycloplegia promoting photophobia and restricted accommodation, which may result in further impairment in visual function. An optimal treatment must ameliorate the long-term ocular insult enabling rapid return of normal visual function, while avoiding the induction of mydriasis and cycloplegia side effects, which could possibly worsen the visual performance. Optimal treatment should also keep effects of misuse to a minimum. Work done in recent years examined treatments with various anticholinergic drugs alone or used in combination with oxime treatments and may offer improved efficacy in ameliorating the ocular insult. This review is a summary of the applied research in animals and will discuss clinical implications and possible alterations in treatment protocols following OP exposure. Taken together the data points toward the use of topical low concentrations of potent anticholinergic ophthalmic drops such as atropine or homatropine, which rapidly ameliorate the long-term OP-induced ocular insult.
How Good Are We in Evaluating a Bedside Head Impulse Test?
Authors: Korda Athanasia , Carey John Patrick , Zamaro Ewa , Caversaccio Marco Domenico , Mantokoudis Georgios 
Published: June 2020

Objectives:
Clinicians performing a horizontal head impulse test (HIT) are looking for a corrective saccade. The detection of such saccades is a challenge. The aim of this study is to assess an expert’s likelihood of detecting corrective saccades in subjects with vestibular hypofunction.

Design:
In a prospective cohort observational study at a tertiary referral hospital, we assessed 365 horizontal HITs performed clinically by an expert neurootologist from a convenience sample of seven patients with unilateral or bilateral deficient vestibulo-ocular reflex (VOR). All HITs were recorded simultaneously by video-oculography, as a gold standard. We evaluated saccades latency and amplitude, head velocity, and gain.

Results:
Saccade amplitude was statistically the most significant parameter for saccade detection (p < 0.001).The probability of saccade detection was eight times higher for HIT toward the pathological side (p = 0.029). In addition, an increase in saccade amplitude resulted in an increased probability of detection (odds ratio [OR] 1.77 [1.31 to 2.40] per degree, p < 0.001). The sensitivity to detect a saccade amplitude of 1 degree was 92.9% and specificity 79%. Saccade latency and VOR gain did not significantly influence the probability of the physician identifying a saccade (OR 1.02 [0.94 to 1.11] per 10-msec latency and OR 0.84 [0.60 to 1.17] per 0.1 VOR gain increase).

Conclusions:
The saccade amplitude is the most important factor for accurate saccade detection in clinically performed head impulse tests. Contrary to current knowledge, saccade latency and VOR gain play a minor role in saccade detection.
Role of Topical Ethanol in the Treatment of Pythium insidiosum Keratitis—A Proof of Concept
Authors: Agarwal Shweta , Srinivasan Bhaskar , Janakiraman Narayanan , Therese Lily K. , S KrishnaKumar , Patel Nilay , V Thenmozhi , Iyer Geetha 
Published: June 2020

Purpose:
To study the efficacy and safety profile of topical absolute ethanol in the treatment of Pythium insidiosum keratitis.

Method:
Microbiological, clinical, and histopathological assessments were performed to study the effects of absolute ethanol on P. insidiosum keratitis. In addition, infrared spectroscopy was performed to assess the corneal penetration of ethanol.

Results:
Microbiological tests revealed that ethanol inhibited the growth of P. insidiosum at concentrations even as low as 20% as compared to Candida albicans and Aspergillus flavus, where minimal growth was noted. However, at 40%, 60%, 80%, and 99.9% of ethanol, complete inhibition of growth was noted for all organisms. Histopathology of the absolute ethanol–treated cadaveric cornea showed the compaction of collagen and no stromal necrosis. Infrared spectroscopy revealed secondary structural changes in collagen in the ethanol-treated cadaveric corneas as compared to controls. Clinically, 1 case with a recurrence of P. insidiosum after therapeutic penetrating keratoplasty resolved with the topical application of absolute ethanol, and the other case, where corneal scraping had grown Pythium within 24 hours, failed to grow the organism from the corneal button which was treated with absolute alcohol preoperatively. After therapeutic penetrating keratoplasty, there was no recurrence, and the graft epithelized well.

Conclusions:
Ethanol can be considered an option for treating P. insidiosum keratitis; however, the exact dose and strength of ethanol which will be most effective needs further work.
Corneal Endothelial Morphology and Thickness Alterations in Patients With Severe Obstructive Sleep Apnea–Hypopnea Syndrome
Authors: Chalkiadaki Evangelia , Andreanos Konstantinos , Florou Chrysoula , Droutsas Konstantinos , Maniou Chrysoula , Amfilochiou Anastasia , Georgalas Ilias , Papaconstantinou Dimitrios , Koutsandrea Chrysanthi 
Published: June 2020

Purpose:
To investigate central endothelial cell density (ECD), morphology, and central corneal thickness (CCT) in patients newly diagnosed with severe obstructive sleep apnea–hypopnea syndrome (OSAHS) and to determine the correlation between these parameters and OSAHS severity.

Methods:
This prospective, comparative case series was conducted in a university ophthalmology clinic. In total, 51 patients recently diagnosed with severe OSAHS (apnea–hypopnea index above 30) and a paired, age and sex-matched control group of 44 healthy individuals were enrolled. After detailed ophthalmologic examination, specular microscopy measurement was performed for all participants. Central ECD, average cell area, coefficient of variation (CV) of cell area, hexagonal cell appearance ratio (% Hex), and CCT were compared between the groups. The Pearson correlation test was also used to assess the influence of the polysomnographic findings, that is, the proportion of each stage of sleep, apnea–hypopnea index, SpO2, mean and maximum duration of apneas, oxygen desaturation index, and arousal index on corneal endothelial morphometric parameters and CCT.

Results:
A total of 190 eyes were examined: 102 eyes of patients with severe OSAHS and 88 eyes of the control group. The mean ECD, CV, % Hex, and CCT values in the OSAHS group were 2439.25 ± 344.36 cells/mm2, 41.41 ± 11.62, 45.22 ± 7.06%, and 533.88 ± 40.53 μm, respectively. ECD and CCT did not significantly differ between the groups (P = 0.46, P = 0.55, respectively). CV value was significantly higher (P = 0.009), whereas the %Hex was significantly lower (P = 0.01) in the OSAHS group. We observed a significant negative correlation between CCT and REM sleep percentage (P = 0.005).

Conclusions:
Greater pleomorphism and polymegathism of corneal endothelium was found in patients with severe OSAHS when compared with healthy subjects. Low percentage of REM sleep, usually found in patients with OSAHS, may cause an increase in corneal thickness.
Multicenter visual outcomes comparison of 2 trifocal presbyopia-correcting IOLs: 6-month postoperative results
Authors: Lapid-Gortzak Ruth , Bhatt Uday , Sanchez Juan Gonzalo , Guarro Mercè , Hida Wilson Takashi , Bala Chandra , Nosé Ricardo Menon , Rodriguez Alvira Francisco Jose , Martinez Aldo 
Published: June 2020

Purpose:
To clinically evaluate visual performance of the AcrySof IQ PanOptix TFNT00 and AT LISA tri 839MP intraocular lenses (IOLs) in binocular visual acuity (VA) and to characterize low-contrast visual performance at 6 months postimplantation.

Setting:
Multicenter, 15 sites.

Design:
Prospective, parallel-group, randomized, double-masked, postmarketing clinical study.

Methods:
Binocular uncorrected distance (UDVA, 4 m), intermediate (UIVA, 60 cm), and near (UNVA, 40 cm) visual acuities and binocular defocus curves were evaluated under photopic lighting conditions. Photopic and mesopic contrast sensitivities with and without glare were assessed.

Results:
The study included 182 subjects (62% women; mean age, 66 ± 9.4 years) who were implanted bilaterally with the TFNT00 IOL (n = 93) or 839MP IOL (n = 89), and binocular VA was evaluated 4 to 6 months (120–180 days) postimplantation. The TFNT00 IOL group showed superior visual outcomes compared with the 839MP IOL group in binocular UIVA (P = .001) and UNVA (P = .003) and noninferior outcomes in UDVA (95% CI, −0.023 to 0.041; upper limit <0.1 logarithm of the minimum angle of resolution [logMAR] [margin of noninferiority]). Mean defocus curve from 0.00 to −3.00 diopter (D) ranged from 0.1 to 0.0 logMAR for both IOLs; better mean VA values (logMAR) were observed in the TFNT00 IOL group between −1.50 and −2.50 D compared with those of the 839MP IOL group. Contrast sensitivity values were similar between the 2 groups in all conditions.

Conclusions:
The results of this study showed improved visual performance at near and intermediate distances with the TFNT00 IOL compared with that of the 839MP IOL.
Perceived Control Prevents Perception of Negative Changes in Life as a Result of Caring for a Patient With Heart Failure
Authors: Chung Misook Lee , Liljeroos Maria , Moser Debra K. , Lennie Terry A. 
Published: June 2020

Introduction
Family caregivers of patients with heart failure (HF) commonly experience emotional distress and caregiving burden. Despite their caregiving distress, caregivers may experience positive or negative changes in their life compared with before caregiving. Greater perceived control is associated with better health outcomes, but little is known about whether perceived control is related to caregivers' perceptions of positive or negative changes in life, independent of their distress and burden in providing care for patients with HF. The specific aims were to compare emotional distress and caregiving burden between caregivers who perceived positive versus negative changes in life due to caregiving and to examine whether perceived control predicts the perception of positive or negative changes in life while controlling for emotional distress and caregiving burden.

Methods
Primary caregivers of patients with HF (N = 140, 75% women) completed questionnaires about perceived positive or negative changes in life as a result of caregiving, perceived control, depressive symptoms, anxiety, and caregiving burden. Independent t test, χ2, and logistic regressions were used to accomplish specific aims.

Results
Compared with caregivers who reported positive changes in life (42%), caregivers who perceived negative changes in life (58%) had higher levels of depressive symptoms, anxiety, and caregiving burden. Lower level of perceived control was an independent predictor of perceived negative changes in life, controlling for age, gender, depressive symptoms, anxiety, and caregiving burden (odds ratio, 0.89; 95% confidence interval, 0.79–0.99; P = .0038).

Conclusion
Greater perceived control played a protective role for caregivers independent of caregiver burden. Interventions designed to enhance perceived control may improve caregivers' perceptions of changes in their life.
Cost-Effectiveness and Return-on-Investment of the Dynamic Work Intervention Compared With Usual Practice to Reduce Sedentary Behavior
Authors: Ben Ângela J. , Jelsma Judith G.M. , Renaud Lidewij R. , Huysmans Maaike A. , van Nassau Femke , van der Beek Allard J. , van der Ploeg Hidde P. , van Dongen Johanna M. , Bosmans Judith E. 
Published: June 2020

Objective:
To assess the cost-effectiveness and return-on-investment (ROI) of the Dynamic Work (DW) Intervention, a worksite intervention aimed at reducing sitting time among office workers.

Methods:
In total, 244 workers were randomized to the intervention or control group. Overall sitting time, standing time, step counts, quality-adjusted life years (QALYs), and costs were measured over 12 months. The cost-effectiveness analysis was performed from the societal perspective and the ROI analysis from the employers’ perspective.

Results:
No significant differences in effects and societal costs were observed between groups. Presenteeism costs were significantly lower in the intervention group. The probability of the intervention being cost-effective was 0.90 at a willingness-to-pay of 20,000€/QALY. The probability of financial savings was 0.86.

Conclusion:
The intervention may be considered cost-effective from the societal perspective depending on the willingness-to-pay. From the employer perspective, the intervention seems cost-beneficial.
Comparison of Measurement Properties of the Mobility Section of the Prosthesis Evaluation Questionnaire on a Visual Analogue Scale and Its Modified Version with Five Response Categories
Authors: Repo Jussi P. , Häkkinen Arja H. , Barner-Rasmussen Ian , Lahdenperä Noora-Ilona , Kautiainen Hannu , Roine Risto P. , Tukiainen Erkki J. 
Published: June 2020

ABSTRACT

Introduction
Two different versions of the Prosthesis Evaluation Questionnaire (PEQ) are available. This study aimed to assess the measurement properties of the original 13-item Mobility Section of the Finnish version of the PEQ on a visual analogue scale (PEQ-VAS, 0–100 points) and its modified 12-item version with five response categories (PEQ-MS12/5, 0–60 points).

Methods
Patients having undergone major lower-limb amputation completed the PEQ, the PEQ-MS12/5, the Locomotor Capabilities Index–5, the Houghton Scale, and the 15D instrument, and answered general health and pain questions on a VAS. Participants who completed the instruments twice in a 2-week interval (n = 117) were included.

Results
Mean (SD) scores of the PEQ-VAS and the PEQ-MS12/5 were 58 (25) and 31 (13) with coefficients of variation of 0.42 and 0.43, respectively. Reproducibility was consistent between the measures. Although Spearman's correlation coefficient was high (r = 0.83) and Kendall's coefficient of concordance was excellent (0.91), differences were noted in score distribution and patient rank correlation. There were similarities and differences in correlations with the other patient-reported instruments.

Conclusions
The original PEQ-VAS Mobility Section and the modified PEQ-MS12/5 have moderate measurement differences; the results are thus not directly comparable. Both measures provide reliable and valid scores, but the modified version is easier to complete and analyze in clinical work.
Efficacy of sofosbuvir/velpatasvir/voxilaprevir in direct-acting antiviral experienced patients with hepatitis C virus
Authors: Da Ben L. , Lourdusamy Vennis , Kushner Tatyana , Dieterich Douglas , Saberi Behnam 
Published: June 2020

Aims
Report the real-world experience of the efficacy and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in chronic hepatitis C virus (HCV) infected patients who have previously experienced a direct-acting antiviral (DAA) containing regimen.

Methods
Consecutive patients who have previously failed or did not tolerate a DAA containing regimen for chronic HCV who was treated with SOF/VEL/VOX were studied. Baseline clinical and laboratory data including NS5A RAS mutation testing were collected.

Results
SOF/VEL/VOX resulted in an end of treatment undetectable HCV viral load in all patients and a sustained virologic response 12 rate of 100% despite the presence of NS5A RAS mutation, HIV infection, and cirrhosis. Treatment with SOF/VEL/VOX was well tolerated and there were no adverse events.

Conclusions
SOF/VEL/VOX is well tolerated and effective in treating patients who have been exposed to prior DAA therapy outside of clinical trials. SOF/VEL/VOX should be considered as the first-line regimen in HCV infected patients who have experienced prior DAA failure.