bluuebunny/crossref_metadata_2025_split huggingface dataset:
MITF controls the TCA cycle to modulate the melanoma hypoxia response
Authors: Louphrasitthiphol Pakavarin , Ledaki Ioanna , Chauhan Jagat , Falletta Paola , Siddaway Robert , Buffa Francesca M. , Mole David R. , Soga Tomoyoshi , Goding Colin R. 
Published: June 2019

AbstractIn response to the dynamic intra‐tumor microenvironment, melanoma cells adopt distinct phenotypic states associated with differential expression of the microphthalmia‐associated transcription factor (MITF). The response to hypoxia is driven by hypoxia‐inducible transcription factors (HIFs) that reprogram metabolism and promote angiogenesis. HIF1α indirectly represses MITF that can activate HIF1α expression. Although HIF and MITF share a highly related DNA‐binding specificity, it is unclear whether they co‐regulate subset of target genes. Moreover, the genomewide impact of hypoxia on melanoma and whether melanoma cell lines representing different phenotypic states exhibit distinct hypoxic responses is unknown. Here we show that three different melanoma cell lines exhibit widely different hypoxia responses with only a core 23 genes regulated in common after 12 hr in hypoxia. Surprisingly, under hypoxia MITF is transiently up‐regulated by HIF1α and co‐regulates a subset of HIF targets including VEGFA. Significantly, we also show that MITF represses itself and also regulates SDHB to control the TCA cycle and suppress pseudo‐hypoxia. Our results reveal a previously unsuspected role for MITF in metabolism and the network of factors underpinning the hypoxic response in melanoma.
Evaluating sunscreen ultraviolet protection using a polychromatic diffuse reflectance device
Authors: Cole Curtis , Silverman Jay , Bonitatibus Michael 
Published: June 2019

AbstractBackgroundSun protection factor (SPF) and UVA protection factor (UVA‐PF) are determined using in vivo tests, with high exposures of subjects to ultraviolet (UV) radiation. Hybrid diffuse reflectance spectroscopy (HDRS) enables estimation of both indices using only trace amounts UVB. However, the equipment requires two expensive monochromators that must synchronously scan the spectrum.MethodsAn alternate approach was developed using a polychromatic source that illuminates the skin via a custom light guide array, and the diffuse reflected light is measured with a photomultiplier. The ratio of the diffuse reflectance with and without the sunscreen on the skin determines the polychromatic diffuse reflectance UVA‐PF (PDRS UVA‐PF0). This factor was used to adjust in vitro UV spectroscopy scans of the sunscreen (with and without UV exposure to assess photostability), to calculate SPF and UVA protection factors. Ten sunscreens were evaluated and compared to in vivo SPF and UVA‐PF values.ResultsThe data show an excellent correlation with known in vivo determinations.ConclusionThis polychromatic HDRS approach uses simpler, faster, and less expensive equipment to determine both UVA‐PF and SPFs without high doses of UV radiation to the test subjects.
Maternal childhood and lifetime traumatic life events and infant bronchiolitis
Authors: Adgent Margaret A. , Elsayed‐Ali Omar , Gebretsadik Tebeb , Tylavsky Frances A. , Kocak Mehmet , Cormier Stephania A. , Wright Rosalind J. , Carroll Kecia N. 
Published: June 2019

AbstractBackgroundViral bronchiolitis is a common respiratory infection that often affects term, otherwise healthy infants. A small literature suggests maternal stress during pregnancy is associated with bronchiolitis. However, the association between maternal exposure to lifetime traumatic stress, including traumatic events occurring in childhood or throughout the life course, and bronchiolitis has not been studied previously.ObjectivesTo investigate the association between maternal exposure to total lifetime and childhood traumatic stress events and infant bronchiolitis.MethodsWe studied mother‐infant dyads enrolled in a prospective prenatal cohort, recruited 2006‐2011, and Tennessee Medicaid. During pregnancy, we assessed maternal lifetime exposure to types of traumatic events by questionnaire. We captured bronchiolitis diagnoses in term, non‐low birthweight infants’ first 12 months using linked Medicaid data. In separate models, we assessed the association of maternal lifetime traumatic events (0 to 20 types) and a subset of traumatic events that occurred during childhood (0 to 3: family violence, sexual, and physical abuse) and infant bronchiolitis using multivariable log‐binomial models.ResultsOf 629 women, 85% were African American. The median count (interquartile range) of lifetime traumatic events was 3 (2, 5); 42% reported ≥1 childhood traumatic event. Among infants, 22% had a bronchiolitis diagnosis (0 to 2 lifetime traumatic events: 24%; 3 events: 20%; 4 to 5 events: 18%; 6 or more events: 24%). Total maternal lifetime traumatic events were not associated with bronchiolitis in multivariable analyses. For maternal childhood traumatic events, the risk of infant bronchiolitis increased with number of event types reported: adjusted Risk ratios were 1.12 (95% confidence interval [CI] 0.80, 1.59), 1.31 (95% CI 0.83, 2.07), and 2.65 (95% CI 1.45, 4.85) for 1, 2, and 3 events, respectively, vs none.ConclusionsInfants born to women reporting multiple types of childhood trauma were at higher risk for bronchiolitis. Further research is needed to explore intergenerational effects of traumatic experiences.
Generalization of fear in post‐traumatic stress disorder
Authors: Lis S. , Thome J. , Kleindienst N. , Mueller‐Engelmann M. , Steil R. , Priebe K. , Schmahl C. , Hermans D. , Bohus M. 
Published: June 2019

AbstractOvergeneralization (i.e., the transfer of fear to stimuli not related to an aversive event) is part of alterations in associative fear learning in mental disorders. In the present experimental study, we investigated whether this holds true for post‐traumatic stress disorder (PTSD) related to childhood abuse. We expected that fear generalization under experimental conditions reflects generalization of aversive stimuli to different social domains in real life. Sixty‐four women with PTSD after childhood abuse and 30 healthy participants (HC) underwent a differential fear conditioning and generalization paradigm. Online risk ratings, reaction time, and fear‐potentiated startle served as dependent variables. Based on the subjectively assessed generalization of triggered intrusions across different domains of life, PTSD participants were split into two groups reporting low (low‐GEN) and high (high‐GEN) generalization. PTSD patients reported a higher expectation of an aversive event. During fear conditioning, they assessed the risk of danger related to a safety cue slower and showed a blunted fear‐potentiated startle toward the danger cue. During generalization testing, reaction time increased in the high‐GEN patients and decreased in the HC group with increasing similarity of a stimulus with the conditioned safety cue. Alterations of fear learning in PTSD suggest impaired defensive responses in case of a high threat probability. Moreover, our findings bridge the gap between the generalization of aversive cues during everyday life and laboratory‐based experimental parameters: impairments in the processing of cues signaling safety generalize particularly in those patients who report a spreading of PTSD symptoms across different domains of everyday life.
Hydroseeding tackifiers and dryland moss restoration potential
Authors: Blankenship W. Dillon , Condon Lea A. , Pyke David A. 
Published: June 2019

Tackifiers are long‐chain carbon compounds used for soil stabilization and hydroseeding and could provide a vehicle for biological soil crust restoration. We examined the sensitivity of two dryland mosses,Bryum argenteumandSyntrichia ruralis,to three common tackifiers—guar, psyllium, and polyacrylamide (PAM)—at 0.5×, 1.0×, and 2.0× of recommended (×) concentrations for erosion control and revegetation. We measured moss shoot, gemma, and protonema production as well as moss organic matter and bound sand masses as indicators of growth and soil holding ability. We tested sand and tackifier chemistry to investigate potential nutrient and toxicant potential on moss growth. Groups of 10 fragments from field‐collected mosses were grown on sand in open petri dishes arranged in a growth chamber in replicated blocks containing each tackifier and concentration combination plus a distilled water control.Bryum(n = 10) andSyntrichia(n = 9) growth were measured at the end of 6 and 5 weeks, respectively. Overall model tests yielded statistically significant results (p < 0.001) for every variable in each species. When compared to water, guar tended to decrease growth, psyllium tended to increase growth, and PAM's effects were generally neutral to positive. Within tackifier types, increasing concentrations of guar tended to decrease growth, while increasing concentrations of psyllium tended to increase growth. Changes in PAM concentrations had little effect on growth. Increases in guar and psyllium lowered pH and increased P and K. Psyllium and PAM yielded promising results as potential agents of dispersal and adherence of dryland mosses in field restoration.
Effect of hyperhydration on the pharmacokinetics and detection of orally administered budesonide in doping control analysis
Authors: Athanasiadou Ioanna , Vonaparti Ariadni , Dokoumetzidis Aristeidis , Saleh Amal , Mbeloug Miriam , Al‐Maadheed Mohammed , Valsami Georgia , Georgakopoulos Costas 
Published: June 2019

The aim of the present study was to investigate if hyperhydration could influence the excretion and subsequent detection of budesonide (BDS) and its main metabolites (6β‐hydroxy‐budesonide and 16α‐hydroxy‐prednisolone) during doping control analysis by leading to concentrations below the WADA reporting level (30 ng/mL). The influence of hyperhydration on the plasma and urinary pharmacokinetic (PK) profiles of BDS and metabolites was also examined. Seven healthy physically active non‐smoking Caucasian males participated in a 15‐day clinical study. BDS was administered orally at a single dose of 9 mg on Days 1, 7, and 13. Hyperhydration was applied in the morning on two consecutive days, that is, 0 and 24 hours after first fluid ingestion. Water and a commercial sports drink were used as hyperhydration agents (20 mL/kg body weight). Results showed no significant difference (P > 0.05, 95% CI) on plasma or urinary PK parameters under hyperhydration conditions for all the analytes. However, significant differences (P < 0.05, 95% CI) due to hyperhydration were observed on the urinary concentrations of BDS and metabolites. To compensate the dilution effect due to hyperhydration, different adjustment methods were applied based on specific gravity, urinary flow rate, and creatinine. All the applied methods were able to adjust the concentration values close to the baseline ones for each analyte; however, specific gravity was the optimum method in terms of effectiveness and practicability. Furthermore, no masking of the detection sensitivity of BDS or its metabolites was observed due to hyperhydration either in plasma or urine samples.
Viable terminal scalp hair follicles constitute a necessary and sufficient biological end‐organ that conditions clinical efficacy of finasteride in males with male pattern hair loss without implying reversal of miniaturized follicles
Authors: Van Neste Dominique 
Published: June 2019

AbstractBackgroundBiopsy‐based “reversal hypothesis” claimed conversion of miniaturized hair follicles into terminal ones for the improvement of male pattern hair loss (MPHL) with FDA‐approved drugs.Materials and methodsMPHL volunteers (n = 13) completed a 24‐month phototrichogram study. After 2 months no‐treatment, panellists took finasteride 1mg daily for 2 years. Hair changes from the best responder would explain the nature of improved hair growth.ResultsDue to the wide range of hair growth variables, no parameter was statistically significantly changed by finasteride in the group. Clinically there were 4 worse, 6 no change, 2 slightly and 1 moderately improved subject associated with turning telogen/empty terminal follicles into anagen after 12‐ and 24‐month finasteride. From 113 miniaturized hair (diameters ≤ 30 µm) at baseline, 79 were still miniature hair after 2 years on finasteride. No hair were found at the remaining mapped sites except for 2 terminal hairs considered a probabilistic “uncertainty.”ConclusionModerate hair improvement resulted from increased productivity of deficient terminal follicles, but not yet irreversibly affected at baseline without implication of miniaturized hair follicles. The latter further regressed even with oral intake of finasteride. The data suggest the rejection of the “reversal hypothesis” unless proven otherwise with duly validated methods.
Intracortical motor networks are affected in both the contralateral and ipsilateral hemisphere during single limb cold water immersion
Authors: Delahunty Eden T , Bisset Leanne M , Kavanagh Justin J 
Published: June 2019

New Findings
What is the central question of this study?
How does single limb cold water immersion affect corticomotor function and intracortical circuitry in the motor cortex of each cerebral hemisphere?

What is the main finding and its importance?
Immersion of a single limb in very cold water caused an increase in corticomotor excitability and intracortical facilitation, and a decrease in intracortical inhibition, in the motor cortex of both hemispheres. These findings provide evidence that intense sensory stimuli induce widespread changes in motor circuitry in the contralateral, as well as the ipsilateral, hemisphere.

AbstractAlthough responses to noxious stimuli have been extensively studied for the contralateral hemisphere, little is known about how the ipsilateral hemisphere may be affected. Therefore, this study examined how exposing a single limb to noxious cold stimuli affects motor output arising from both the contralateral and ipsilateral hemisphere. A total of 17 healthy adults participated in three experiments. Single‐ and paired‐pulse TMS protocols were used to identify how immersing a single upper limb in cold water (4.0 ± 0.5 °C) affects inhibitory and facilitatory circuits in the primary motor cortex (M1) of the contralateral (experiment 1) and ipsilateral (experiment 2) hemisphere. The third experiment used a reaction time task to assess the functional consequences of acute adaptations in the ipsilateral M1. The target muscle in all experiments was the extensor carpi radialis brevis (ECRB). Immersion of a single limb in cold water increased self‐perception of pain and temperature, and increased EMG amplitude of the immersed limb. During immersion, motor evoked potentials and intracortical facilitation increased, whereas short interval intracortical inhibition decreased, for both the ipsilateral M1 and contralateral M1. Activity in the ipsilateral hemisphere to the limb immersed in cold water also slowed reaction time for the non‐immersed limb. Our findings suggest that altered motor responses from single limb cold water immersion are not restricted to a single hemisphere. Instead, widespread activation of somatosensory systems influences inhibitory and facilitatory circuits in the primary motor cortex of each hemisphere.
Scaling, Growth, and Size Effects on the Mechanical Behavior of a Topologically Interlocking Material Based on Tetrahedra Elements
Authors: Short M. , Siegmund T. 
Published: June 2019

AbstractThe present study is concerned with the deformation response of an architectured material system, i.e., a 2D-material system created by the topological interlocking assembly of polyhedra. Following the analogy of granular crystals, the internal load transfer is considered along well-defined force networks, and internal equivalent truss structures are used to describe the deformation response. Closed-form relationships for stiffness, strength, and toughness of the topologically interlocked material system are presented. The model is validated relative to direct numerical simulation results. The topologically interlocked material system characteristics are compared with those of monolithic plates. The architectured material system outperforms equivalent size monolithic plates in terms of toughness for nearly all possible ratios of modulus to the strength of the material used to make the building blocks and plate, respectively. In addition, topologically interlocked material systems are shown to provide better strength characteristics than a monolithic system for low strength solids.
Thermally Actuated Hierarchical Lattices With Large Linear and Rotational Expansion
Authors: Xu Hang , Farag Amr , Ma Ruizhe , Pasini Damiano 
Published: June 2019

Abstract
This paper presents thermally actuated hierarchical metamaterials with large linear and rotational motion made of passive solids. Their working principle relies on the definition of a triangular bi-material unit that uses temperature changes to locally generate in its internal members distinct rates of expansion that translate into anisotropic motions at the unit level and large deployment at the global scale. Obtained from solid mechanics theory, thermal experiments on fabricated proof-of-concepts and numerical analysis, the results show that introducing recursive patterns of just two orders of the hierarchy is highly effective in amplifying linear actuation at levels of nearly nine times the initial height, and rotational actuation of almost 18.5 times the initial skew angle.
Advances in rehabilitation for chronic diseases: improving health outcomes and function
Authors: Richardson Caroline R , Franklin Barry , Moy Marilyn L , Jackson Elizabeth A 
Published: June 2019

AbstractMuch of the burden on healthcare systems is related to the management of chronic conditions such as cardiovascular disease and chronic obstructive pulmonary disease. Although conventional outpatient cardiopulmonary rehabilitation programs significantly decrease morbidity and mortality and improve function and health related quality of life for people with chronic diseases, rehabilitation programs are underused. Barriers to enrollment are multifactorial and include failure to recommend and refer patients to these services; poor communication with patients about potential benefits; and patient factors including logistical and financial barriers, comorbidities, and competing demands that make participation in facility based programs difficult. Recent advances in rehabilitation programs that involve remotely delivered technology could help deliver services to more people who might benefit. Problems with intensity, adherence, and safety of home based programs have been investigated in recent clinical trials, and larger dissemination and implementation trials are under way. This review summarizes the evidence for benefit of in-person cardiac and pulmonary rehabilitation programs. It also reviews the literature on newer developments, such as home based remotely mediated exercise programs developed to decrease cost and improve accessibility, high intensity interval training in cardiac rehabilitation, and alternative therapies such as tai chi and yoga for people with chronic obstructive pulmonary disease.
Teaching medical students to recognise and report errors
Authors: Mohsin Syed Umer , Ibrahim Yahya , Levine Diane 
Published: June 2019

BackgroundMedical student error reporting can potentially be increased through patient safety education, culture change and by teaching students how to report errors. There is scant literature on what kinds of errors students see during clinical rotations. The authors developed an intervention to better understand what kinds of errors students see and to train them to identify and report errors.MethodsA safety curriculum was delivered during the Medicine clerkship for the academic year 2015–2016. Prior to the workshop, students completed a preintervention survey to determine whether they had reported a clinical error. Subsequently, they participated in an educational workshop. Facilitated discussions about conditions contributing to errors, types of errors, prevention of errors and importance of reporting followed. Students were required to submit a simulated error report about an error they personally observed. An end-of-year survey was sent to students who participated in the curriculum to determine clinical error reporting frequency.ResultsStudents submitted 282 reports. Near miss errors were seen in 64% and adverse events in 36%. National Quality Forum serious events were reported in 14%, including one death. Recommendations to prevent similar events were weak (62%). Students correctly categorised 93% near miss, 88% adverse events, 67% diagnostic, 81% treatment and 78% preventative errors. On the preintervention survey, 8.5% stated they submitted an error report to their clinical site. On the end-of-year survey, 18% confirmed submitting a formal error report.ConclusionTraining students to recognise and report errors can be successfully integrated into a clinical clerkship and impact clinical error reporting.
Are battlefield and prehospital trauma scenarios an effective educational tool to teach leadership and crisis resource management skills to undergraduate medical students?
Authors: Ellington Matt , Farrukh S 
Published: June 2019

IntroductionLeadership and crisis resource management (CRM) skills are important skills for doctors, however there is a recognised lack of undergraduate leadership education. There remains debate over how best to teach leadership and CRM skills, and poor leadership skills among clinicians are associated with adverse patient outcomes. We examined whether high-fidelity battlefield and prehospital scenarios can improve leadership and CRM skills.MethodThis was a prospective observational study with students self-reporting their leadership and CRM skills using the Ottawa Crisis Resource Management Global Ranking Scale (OCRMGRS) before and after completing the Cambridge University Emergency Medicine Society Battlefield and Pre-Hospital Trauma course. The course involves a mixture of small group tutorials and practical high-fidelity battlefield and prehospital trauma scenarios. Faculty also completed the OCRMGRS for the first and last candidates at the scenarios. The mean precourse versus mean postcourse score of the OCRMGRS was analysed using a two-tailed t-test.Results46 students completed paired OCRMGRS before and after the course. The mean precourse scores for each of the domains (leadership, communication skills, resource utilisation, problem solving skills and situational awareness) were calculated. There was a statistically significant (p<0.05) increase in both self-reported and faculty-reported scores across all domains, and the increase remained at 1-year follow-up.ConclusionsLeadership and CRM skills are important non-clinical skills for doctors, however there is debate over how best to teach them. High-fidelity battlefield and prehospital trauma scenarios are an effective means of teaching leadership and CRM skills to civilian medical students.