bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cap‐independent translation: A shared mechanism for lifespan extension by rapamycin, acarbose, and 17α‐estradiol
Authors: Shen Ziqian , Hinson Abby , Miller Richard A. , Garcia Gonzalo G. 
Published: March 2021

AbstractWe hypothesized that rapamycin (Rapa), acarbose (ACA), which both increase mouse lifespan, and 17α‐estradiol, which increases lifespan in males (17aE2) all share common intracellular signaling pathways with long‐lived Snell dwarf, PAPPA‐KO, and Ghr−/− mice. The long‐lived mutant mice exhibit reduction in mTORC1 activity, declines in cap‐dependent mRNA translation, and increases in cap‐independent translation (CIT). Here, we report that Rapa and ACA prevent age‐related declines in CIT target proteins in both sexes, while 17aE2 has the same effect only in males, suggesting increases in CIT. mTORC1 activity showed the reciprocal pattern, with age‐related increases blocked by Rapa, ACA, and 17aE2 (in males only). METTL3, required for addition of 6‐methyl‐adenosine to mRNA and thus a trigger for CIT, also showed an age‐dependent increase blunted by Rapa, ACA, and 17aE2 (in males). Diminution of mTORC1 activity and increases in CIT‐dependent proteins may represent a shared pathway for both long‐lived‐mutant mice and drug‐induced lifespan extension in mice.
The phenotype of recovery V: Does delay discounting predict the perceived risk of relapse among individuals in recovery from alcohol and drug use disorders
Authors: Turner Jamie K. , Athamneh Liqa N. , Basso Julia C. , Bickel Warren K. 
Published: March 2021

AbstractBackgroundSubstance use recovery is a dynamic process. Relapse, often part of the recovery process, is a persistent problem for individuals seeking freedom from their harmful substance use and has become a focus of research on the improvement of recovery outcomes. Delay discounting is associated with substance use disorder severity, both its negative outcomes and the propensity to relapse. However, the association between delay discounting and perceived risk of relapse as measured by the Alcohol Warning of Relapse Questionnaire has not previously been examined in a population of individuals in long‐term recovery from substance misuse.MethodsIn this study, using data collected from the International Quit and Recovery Registry, we investigated the association between delay discounting, self‐reported time in recovery, and perceived risk of relapse. Data from 193 individuals self‐reporting to be in recovery from harmful substance use were included in the study.ResultsDelay discounting rates were significantly negatively associated with length of recovery (p = 0.036) and positively with perceived risk of relapse (p = 0.027) even after controlling for age, gender, education, marital status, ethnicity, race, primary substance, and length in the registry. Moreover, a mediation analysis using Hayes’ methods revealed that the association between the length of recovery and perceived relapse risk was partially mediated by delay discounting, accounting for 21.2% of the effect.ConclusionsOur finding supports previous characterizations of delay discounting as a candidate behavioral marker of substance misuse and may help to identify individuals at higher perceived risk of relapse in an extended recovery population.
Estimating temperature effects on Drosophila suzukii life cycle parameters
Authors: Winkler Alicia , Jung Jeanette , Kleinhenz Benno , Racca Paolo 
Published: March 2021

Drosophila suzukii is an invasive, polyphagous pest of soft‐skinned fruits, having huge impact on fruit production in Asia, North and South America and Europe including Germany.
To investigate the effect of temperature on oviposition, egg‐to‐adult development success and duration, as well as immature heat survival and adult cold survival for a German D. suzukii population several experiments were conducted under different constant temperatures in the laboratory. The resulting life cycle data were described mathematically as functions of temperature and compared with experimental results of other researchers in a summary table.
Curve fittings used herein revealed that minimum, optimum and maximum temperatures are: 13.2, 26.7 and 33.6 °C for oviposition, 14.1, 22.6 and 30.0 °C for egg‐to‐adult development success, and 9.6, 27.3 and 35.7 °C for egg‐to‐adult development duration. Eggs and larvae of D. suzukii showed a reduced heat survival within the tested temperature range of 29 to 41 °C and exposure durations from 1 to 8 h. A cold survival rate of 50% was measured at e.g. −6 °C for 4 h in summer morph adults and at e.g. −6 °C for 45 h in winter morph adults confirming that the latter are more cold tolerant.
Results obtained in this study for a German population of D. suzukii are similar to those obtained for populations of other origins such as Canada, Japan, Spain and USA. Thus, presumably, present data based on a German D. suzukii population can be used for a new or fine‐tune of already existing population dynamics models of D. suzukii in order to support an effective pest management strategy.
“Mask up to keep it up”: Preliminary evidence of the association between erectile dysfunction and COVID‐19
Authors: Sansone Andrea , Mollaioli Daniele , Ciocca Giacomo , Colonnello Elena , Limoncin Erika , Balercia Giancarlo , Jannini Emmanuele A. 
Published: March 2021

AbstractBackgroundErectile dysfunction (ED), as the hallmark of endothelial dysfunction, could be a short‐ or long‐term complication of COVID‐19. Additionally, being ED a clinical marker and predictor of non‐communicable chronic diseases, particularly cardiovascular, subjects with ED could potentially have a higher risk of contracting COVID‐19.ObjectivesTo investigate the prevalence of ED among subjects with a reported diagnosis of COVID‐19 and to measure the association of COVID‐19 and ED.Materials and methodsWe reviewed data from the Sex@COVID online survey (performed between April 7 and May 4, 2020, in Italy) to retrieve a sample of Italian male sexually active subjects with reported SARS‐CoV‐2 infection. A matching sample of COVID‐19‐negative male sexually active subjects was also retrieved using propensity score matching in a 3:1 ratio. The survey used different standardized psychometric tools to measure effects of lockdown and social distancing on the intrapsychic, relational, and sexual health of Italian subjects.ResultsOne hundred subjects were included in the analysis (25 COVID‐positive; 75 COVID‐negative). The prevalence of ED, measured with the Sexual Health Inventory for Men, was significantly higher in the COVID+ group (28% vs. 9.33%; p = 0.027). Logistic regression models confirmed a significant effect of COVID‐19 on the development of ED, independently of other variables affecting erectile function, such as psychological status, age, and BMI [OR 5.66, 95% CI: 1.50–24.01]. Likewise, subjects with ED were more likely to have COVID‐19, once corrected for age and BMI [OR 5.27, 95% CI: 1.49–20.09].Discussion and conclusionOn top of well‐described pathophysiological mechanisms, there is preliminary evidence in a real‐life population of ED as a risk factor of developing COVID‐19 and possibly occurring as a consequence of COVID‐19. Universal vaccination against the COVID‐19 and the personal protective equipment could possibly have the added benefit of preventing sexual dysfunctions.
Circumferential (360°) trabeculotomy in primary congenital glaucoma: 19–245 months of follow‐up
Authors: Tønset Turid Skei , Jakobsen Jan Erik , Tveit Jon Henrik , Jørstad Anna‐Katharina L. , Brevik Tone Beate , Sten Lotte‐Guri Bogfjellmo , Drolsum Liv 
Published: March 2021

AbstractPurposeTo evaluate the long‐term efficacy and safety of circumferential trabeculotomy (CT) in the treatment of primary congenital glaucoma (PCG).MethodsRetrospective, single‐institutional case series of CT performed for PCG in years 1997–2016. The surgery could be completed in 42 out of 65 eyes (65%) intended for CT, and 39 of them were included in the study. A follow‐up examination was performed in 2017. Success was defined as intraocular pressure ≤ 16 mmHg without (complete) or with (qualified) glaucoma medication.ResultsComplete success was obtained in 33/39 eyes (85%), qualified success in 34/39 eyes (87%). Of the 39 eyes with CT, 4 eyes (10%) needed additional surgery. Median follow‐up time was 120 months (range, 19–245 months). Median pre‐ and postoperative IOP were 26.0 mmHg (range, 10–41 mmHg) and 11.0 mmHg (range, 8–19 mmHg), respectively (p < 0.001). Cup‐disc ratio was ≥0.5 in 82% at baseline, at follow‐up in 9%. The median distance corrected visual acuity at follow‐up was logMAR 0.06 (range, −0.2 to 1.1). Median number of glaucoma medication at follow‐up was 0 (range, 0–2), at baseline 1.0 (range, 0–2). No serious complications were noted.ConclusionCircumferential trabeculotomy is an efficacious, safe and medication saving surgical treatment for PCG in the long term. After a median follow‐up of 10 years (120 months), the morphological status of the optic nerve was either normalized or stabilized, and the visual acuity overall well preserved.
High rates of antibiotic prescriptions in children with COVID‐19 or multisystem inflammatory syndrome: A multinational experience in 990 cases from Latin America
Authors: Yock‐Corrales Adriana , Lenzi Jacopo , Ulloa‐Gutiérrez Rolando , Gómez‐Vargas Jessica , Antúnez‐Montes Omar Yassef , Rios Aida Jorge Alberto , del Aguila Olguita , Arteaga‐Menchaca Erick , Campos Francisco , Uribe Fadia , Parra Buitrago Andrea , Maria Betancur Londoño Lina , Brizuela Martin , Buonsenso Danilo 
Published: March 2021

AbstractAimThis study aims to assess rates of antibiotic prescriptions and its determinants in in children with COVID‐19 or Multisystem Inflammatory Syndrome (MIS‐C).MethodsChildren <18 years‐old assessed in five Latin Americas countries with a diagnosis of COVID‐19 or MIS‐C were enrolled. Antibiotic prescriptions and factors associated with their use were assessed.ResultsA total of 990 children were included: 921 (93%) with COVID‐19, 69 (7.0%) with MIS‐C. The prevalence of antibiotic use was 24.5% (n = 243). MIS‐C with (OR = 45.48) or without (OR = 10.35) cardiac involvement, provision of intensive care (OR = 9.60), need for hospital care (OR = 6.87), pneumonia and/or ARDS detected through chest X‐rays (OR = 4.40), administration of systemic corticosteroids (OR = 4.39), oxygen support, mechanical ventilation or CPAP (OR = 2.21), pyrexia (OR = 1.84), and female sex (OR = 1.50) were independently associated with increased use of antibiotics. There was significant variation in antibiotic use across the hospitals.ConclusionOur study showed a high rate of antibiotic prescriptions in children with COVID‐19, in particular in those with severe disease or MIS‐C. Prospective studies are needed to provide better evidence on the recognition and management of bacterial infections in COVID‐19 children.
Quality of life, mental health, and family functioning of schizophrenia caregivers: A community‐based cross‐sectional study
Authors: Khatimah Cut Husnul , Adami Aulina , Abdullah Asnawi , Marthoenis  
Published: March 2021

AbstractThe caregivers of people with schizophrenia might suffer from various problems. We investigated the prevalence of depression, anxiety, and stress among them, and factors associated with their quality of life. A cross‐sectional study in communities of rural areas was conducted. We found that the prevalence of depression, anxiety, and stress were 14.2%, 25.5%, and 6.6%, respectively. Their quality of life was independently associated with family functioning (affective responsiveness, problem solving, communication) and the presence of depressive symptoms (p < .05). Schizophrenia caregivers need more supports from health care professionals to improve their skills in problem solving.
Acute toxicity and micronucleus test of conotoxin lt14a in mice
Authors: Wu Yun , Qiang Yuanyuan , Zhang Guangxian , Zhou Maojun 
Published: March 2021

AbstractConotoxins, which target ion channels or neurotransmitter receptors with high specificity, are valuable in drug development for pain, epilepsy and other neurological diseases. However, the toxicology of conotoxins is rarely reported. In this study, we primarily researched parts of the pharmacological and toxicological properties of an analgesic conotoxin lt14a. Three doses of lt14a (1, 5 and 10 mg/kg) could prolong the pentobarbital‐induced sleep time of mice and showed no significant effect on the spontaneous locomotor activity of mice. Three doses of lt14a (50, 100 and 200 mg/kg) did not increase micronucleus rate in the micronucleus test. In addition, three doses of lt14a (200, 500 and 1000 mg/kg) showed no pathological change on the heart or brain of mice in the acute toxicity test. The high dose of lt14a (1000 times the effective analgesic dose) had a certain damaging effect on the liver and lung according to serological detection and histopathology. As part of the preclinical studies, our results provide acute toxicity and mutagenicity evaluation of the promising analgesic conotoxin lt14a.
Fluorescent‐ and tagged‐protoxin II peptides: potent markers of the Nav1.7 channel pain target
Authors: Montnach Jérôme , De Waard Stephan , Nicolas Sébastien , Burel Sophie , Osorio Nancy , Zoukimian Claude , Mantegazza Massimo , Boukaiba Rachid , Béroud Rémy , Partiseti Michel , Delmas Patrick , Marionneau Céline , De Waard Michel 
Published: March 2021

Background and PurposeProtoxin II (ProTx II) is a high affinity gating modifier that is thought to selectively block the Nav1.7 voltage‐dependent Na+ channel, a major therapeutic target for the control of pain. We aimed at producing ProTx II analogues entitled with novel functionalities for cell distribution studies and biochemical characterization of its Nav channel targets.Experimental ApproachWe took advantage of the high affinity properties of the peptide, combined to its slow off rate, to design a number of new tagged analogues useful for imaging and biochemistry purposes. We used high‐throughput automated patch‐clamp to identify the analogues best matching the native properties of ProTx II and validated them on various Nav‐expressing cells in pull‐down and cell distribution studies.Key ResultsTwo of the produced ProTx II analogues, Biot‐ProTx II and ATTO488‐ProTx II, best emulate the pharmacological properties of unlabelled ProTx II, whereas other analogues remain high affinity blockers of Nav1.7. The biotinylated version of ProTx II efficiently works for the pull‐down of several Nav isoforms tested in a concentration‐dependent manner, whereas the fluorescent ATTO488‐ProTx II specifically labels the Nav1.7 channel over other Nav isoforms tested in various experimental conditions.Conclusions and ImplicationsThe properties of these ProTx II analogues as tools for Nav channel purification and cell distribution studies pave the way for a better understanding of ProTx II channel receptors in pain and their pathophysiological implications in sensory neuronal processing. The new fluorescent ProTx II should also be useful in the design of new drug screening strategies.
A retrospective analysis of actionable pharmacogenetic/genomic biomarker language in FDA labels
Authors: Yamazaki Shinji 
Published: March 2021

AbstractThe primary goal of precision medicine is to maximize the benefit‐risk relationships for individual patients by delivering the right drug to the right patients at the right dose. To achieve this goal, it has become increasingly important to assess gene‐drug interactions (GDIs) in clinical settings. The US Food and Drug Administration (FDA) periodically updates the table of pharmacogenetic/genomic (PGx) biomarkers in drug labeling on their website. As described herein, an effort was made to categorize various PGx biomarkers covered by the FDA‐PGx table into certain groups. There were 2 major groups, oncology molecular targets (OMT) and drug‐metabolizing enzymes and transporters (DMETs), which constitute ~70% of all biomarkers (~33% and ~35%, respectively). These biomarkers were further classified whether their labeling languages could be actionable in clinical practice. For OMT biomarkers, ~70% of biomarkers are considered actionable in clinical practice as they are critical for the selection of appropriate drugs to individual patients. In contrast, ~30% of DMET biomarkers are considered actionable for the dose adjustments or alternative therapies in specific populations, such as CYP2C19 and CYP2D6 poor metabolizers. In addition, the GDI results related to some of the other OMT and DMET biomarkers are considered to provide valuable information to clinicians. However, clinical GDI results on the other DMET biomarkers can possibly be used more effectively for dose recommendation. As the labels of some drugs already recommend the precise doses in specific populations, it will be desirable to have clear language for dose recommendation of other (or new) drugs if appropriate.
Identification of small molecules that mitigate vincristine‐induced neurotoxicity while sensitizing leukemia cells to vincristine
Authors: Diouf Barthelemy , Wing Claudia , Panetta John C. , Eddins Donnie , Lin Wenwei , Yang Wenjian , Fan Yiping , Pei Deqing , Cheng Cheng , Delaney Shannon M. , Zhang Wei , Bonten Erik J. , Crews Kristine R. , Paugh Steven W. , Li Lie , Freeman Burgess B. , Autry Robert J. , Beard Jordan A. , Ferguson Daniel C. , Janke Laura J. , Ness Kirsten K. , Chen Taosheng , Zakharenko Stanislav S. , Jeha Sima , Pui Ching‐Hon , Relling Mary V. , Eileen Dolan M. , Evans William E. 
Published: March 2021

AbstractVincristine (VCR) is one of the most widely prescribed medications for treating solid tumors and acute lymphoblastic leukemia (ALL) in children and adults. However, its major dose‐limiting toxicity is peripheral neuropathy that can disrupt curative therapy. Peripheral neuropathy can also persist into adulthood, compromising quality of life of childhood cancer survivors. Reducing VCR‐induced neurotoxicity without compromising its anticancer effects would be ideal. Here, we show that low expression of NHP2L1 is associated with increased sensitivity of primary leukemia cells to VCR, and that concomitant administration of VCR with inhibitors of NHP2L1 increases VCR cytotoxicity in leukemia cells, prolongs survival of ALL xenograft mice, but decreases VCR effects on human‐induced pluripotent stem cell‐derived neurons and mitigates neurotoxicity in mice. These findings offer a strategy for increasing VCR’s antileukemic effects while reducing peripheral neuropathy in patients treated with this widely prescribed medication.
Angiotensin 1‐7 protects against ventilator‐induced diaphragm dysfunction
Authors: Yoshihara Toshinori , Deminice Rafael , Hyatt Hayden W. , Ozdemir Mustafa , Nguyen Branden L. , Powers Scott K. 
Published: March 2021

AbstractMechanical ventilation (MV) is a life‐saving instrument used to provide ventilatory support for critically ill patients and patients undergoing surgery. Unfortunately, an unintended consequence of prolonged MV is the development of inspiratory weakness due to both diaphragmatic atrophy and contractile dysfunction; this syndrome is labeled ventilator‐induced diaphragm dysfunction (VIDD). VIDD is clinically important because diaphragmatic weakness is an important contributor to problems in weaning patients from MV. Investigations into the pathogenesis of VIDD reveal that oxidative stress is essential for the rapid development of VIDD as redox disturbances in diaphragm fibers promote accelerated proteolysis. Currently, no standard treatment exists to prevent VIDD and, therefore, developing a strategy to avert VIDD is vital. Guided by evidence indicating that activation of the classical axis of the renin‐angiotensin system (RAS) in diaphragm fibers promotes oxidative stress and VIDD, we hypothesized that activation of the nonclassical RAS signaling pathway via angiotensin 1‐7 (Ang1‐7) will protect against VIDD. Using an established animal model of prolonged MV, our results disclose that infusion of Ang1‐7 protects the diaphragm against MV‐induced contractile dysfunction and fiber atrophy in both fast and slow muscle fibers. Further, Ang1‐7 shielded diaphragm fibers against MV‐induced mitochondrial damage, oxidative stress, and protease activation. Collectively, these results reveal that treatment with Ang1‐7 protects against VIDD, in part, due to diminishing oxidative stress and protease activation. These important findings provide robust evidence that Ang1‐7 has the therapeutic potential to protect against VIDD by preventing MV‐induced contractile dysfunction and atrophy of both slow and fast muscle fibers.
Bribery, hold‐up, and bureaucratic structure
Authors: Bennett John , Rablen Matthew D. 
Published: March 2021

AbstractWe consider infrastructure provision by a foreign investor when the domestic bureaucracy is corrupt, but also cares for domestic welfare. Bureaucrats bargain with the investor over price and (potentially) bribes, both before the investment is sunk and afterwards, using the threat of expropriation. We show that domestic welfare may be greater in equilibria with bribery than in equilibria without. We specify conditions under which changes in the degree of bureaucratic centralization or of bureaucratic care have a positive, negative, or nonmonotonic effect on domestic welfare. The impact of centralization on domestic welfare is mediated through the level of bureaucratic care.
The real effects of liquidity: Puerto Rico as a natural experiment
Authors: Ramirez Carlos D. 
Published: March 2021

AbstractThis paper investigates the consequences of a large and sustained liquidity infusion on the real economy using Section 936 tax incentives in Puerto Rico as a natural experiment. I find that the tax incentives increased liquidity and lowered the cost of funds for PR banks. Furthermore, 936 funds stimulated C&I and real estate loans. However, the incidence of troubled loans increases with the amount of 936 funds received, pointing to excessive and inefficient financing in those sectors. The implementation and subsequent removal of these incentives induced a structural shift in Puerto Rico's economy, generating an unintended and long‐lasting boom‐bust cycle.
Effects of affective content and motivational context on neural gain functions during naturalistic scene perception
Authors: Tebbe Anna‐Lena , Friedl Wendel M. , Alpers Georg W. , Keil Andreas 
Published: March 2021

AbstractVisual scene processing is modulated by semantic, motivational, and emotional factors, in addition to physical scene statistics. An open question is to what extent those factors affect low‐level visual processing. One index of low‐level visual processing is the contrast response function (CRF), representing the change in neural or psychophysical gain with increasing stimulus contrast. Here we aimed to (a) establish the use of an electrophysiological technique for assessing CRFs with complex emotional scenes and (b) examine the effects of motivational context and emotional content on CRFs elicited by naturalistic stimuli, including faces and complex scenes (humans, animals). Motivational context varied by expectancy of threat (a noxious noise) versus safety. CRFs were measured in 18 participants by means of sweep steady‐state visual evoked potentials. Results showed a facilitation in visuocortical sensitivity (contrast gain) under threat, compared with safe conditions, across all stimulus categories. Facial stimuli prompted heightened neural response gain, compared with scenes. Within the scenes, response gain was smaller for scenes high in emotional arousal, compared with low‐arousing scenes, consistent with interference effects of emotional content. These findings support the notion that motivational context alters the contrast sensitivity of cortical tissue, differing from changes in response gain (activation) when visual cues themselves carry motivational/affective relevance.