Miracle-dz/UniFAR-FTUs huggingface dataset:
Cholinergic modulation of striatal nitric oxide‐producing interneurons

Striatal GABAergic interneurons that express nitric oxide synthase—so‐called low‐threshold spike interneurons (LTSIs)—play several key roles in the striatum. But what drives the activity of these interneurons is less well defined. To fill this gap, a combination of monosynaptic rabies virus mapping (msRVm), electrophysiological and optogenetic approaches were used in transgenic mice in which LTSIs expressed either Cre recombinase or a fluorescent reporter. The rabies virus studies revealed a striking similarity in the afferent connectomes of LTSIs and neighboring cholinergic interneurons, particularly regarding connections arising from the parafascicular nucleus of the thalamus and cingulate cortex. While optogenetic stimulation of cingulate inputs excited both cholinergic interneurons and LTSIs, thalamic stimulation excited cholinergic interneurons, but inhibited LTSIs. This inhibition was dependent on cholinergic interneurons and had two components: a previously described GABAergic element and one that was mediated by M4 muscarinic acetylcholine receptors. In addition to this phasic signal, cholinergic interneurons tonically excited LTSIs through a distinct, M1 muscarinic acetylcholine receptor pathway. This coordinated cholinergic modulation of LTSIs predisposed them to rhythmically burst in response to phasic thalamic activity, potentially reconfiguring striatal circuitry in response to salient environmental stimuli.
Precooling, Hyperthermia, and Postexercise Cooling Rates in Humans Wearing American Football Uniforms.

CONTEXT Exertional heatstroke is one of the leading causes of death in American football players. Precooling (PC) with whole-body cold-water immersion (CWI) may prevent severe hyperthermia and, possibly, exertional heatstroke. However, it is unknown how much PC delays severe hyperthermia when participants wear American football uniforms during exercise in the heat. Does PC alter the effectiveness of CWI once participants become hyperthermic or affect perceptual variables during exercise? OBJECTIVES We asked 3 questions: (1) Does PC affect how quickly participants become hyperthermic during exercise in the heat? (2) Does PC before exercise affect rectal temperature (Trec) cooling rates once participants become hyperthermic? (3) Does PC affect perceptual variables like rating of perceived exertion (RPE), thermal sensation, and environmental symptom questionnaire (ESQ) responses? DESIGN Crossover study. SETTING Laboratory. PATIENTS OR OTHER PARTICIPANTS Twelve physically active males (age = 24 ± 4 years, height = 181.8 ± 8.4 cm, mass = 79.9 ± 10.3 kg). INTERVENTION(S) On PC days, participants completed 15 minutes of CWI (9.98°C ± 0.04°C). They donned American football uniforms and exercised in the heat (temperature = 39.1°C ± 0.3°C, relative humidity = 36% ± 2%) until Trec was 39.5°C. While wearing equipment, they then underwent CWI until Trec was 38°C. Control-day procedures were the same except for the PC intervention. MAIN OUTCOME MEASURE(S) Rectal temperature, heart rate, thermal sensation, RPE, and ESQ responses were measured throughout testing. The duration of cold-water immersion was used in conjunction with Trec to calculate cooling rates. RESULTS Precooling allowed participants to exercise 17.6 ± 3.6 minutes longer before reaching 39.5°C (t11 = 17.0, P < .001). Precooling did not affect postexercise CWI Trec cooling rates (PC = 0.18°C/min ± 0.06°C/min, control = 0.20°C/min ± 0.09°C/min; t11 = 0.9, P = .17); ESQ responses (F2,24 = 1.3, P = .3); or RPE (F2,22 = 2.9, P = .07). Precooling temporarily lowered thermal sensation (F3,26 = 21.7, P < .001) and heart rate (F3,29 = 21.0, P < .001) during exercise. CONCLUSIONS Because PC delayed hyperthermia without negatively affecting perceptual variables or CWI effectiveness, clinicians may consider implementing PC along with other proven strategies for preventing heat illness (eg, acclimatization).
Autophagy in Neurons.

Autophagy is the major cellular pathway to degrade dysfunctional organelles and protein aggregates. Autophagy is particularly important in neurons, which are terminally differentiated cells that must last the lifetime of the organism. There are both constitutive and stress-induced pathways for autophagy in neurons, which catalyze the turnover of aged or damaged mitochondria, endoplasmic reticulum, other cellular organelles, and aggregated proteins. These pathways are required in neurodevelopment as well as in the maintenance of neuronal homeostasis. Here we review the core components of the pathway for autophagosome biogenesis, as well as the cell biology of bulk and selective autophagy in neurons. Finally, we discuss the role of autophagy in neuronal development, homeostasis, and aging and the links between deficits in autophagy and neurodegeneration. Expected final online publication date for the Annual Review of Cell and Developmental Biology Volume 35 is October 7, 2019. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Self-concept clarity lays the foundation for self-continuity: The restorative function of autobiographical memory.

The current research concerns the relations among self-concept clarity, autobiographic memory, and self-continuity. We hypothesized, and tested in 7 studies, that low self-concept clarity would disrupt self-continuity, but resorting to autobiographic memory would counter this disruption, thus restoring self-continuity. In Studies 1 and 2, low or threatened self-concept clarity was associated with decreased, or led to a decrease of, self-continuity. In Study 3, participants low (vs. high) in self-concept clarity manifested a stronger preference for an autobiographical memory task (but not for a control task). In Study 4, a suppressed mediational model of autobiographical memory received empirical backing: Threatened self-concept clarity decreased self-continuity, but also increased the propensity to evoke autobiographical memory, which fostered self-continuity. By manipulating autobiographical memory in different ways, Studies 5 through 7 provided additional direct evidence for the capacity of autobiographical memory to restore self-continuity. Taken together, the results converge in support of the hypothesis. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Olfactory Fossa and New Angle Measurements: Lateral Lamella-Cribriform Plate Angle.

OBJECTIVES The authors investigated the olfactory fossa (OF) in patients with unilateral nasal septal deviation (NSD) and presented the lateral lamella-cribriform plate angle (LLCPA). METHODS Paranasal sinus computed tomography images of 300 adult subjects with unilateral NSD (111 males, 189 females) were evaluated retrospectively. Septal deviation angle (SDA), Keros Classification, OF depth and width, LLCPA; and orbital plate and cribriform plate (OPCP) distance were measured. RESULTS The OF depth values (ipsilateral, contralateral) were found as Keros III >Keros II >Keros I (Padjusted <0.0175). The OF width values (ipsilateral) were detected as Keros I >Keros II and Keros I >Keros III (Padjusted <0.0175). In patients with higher SDA values, ipsilateral OF depth values decreased (P <0.05). The LLCPA and OPCP values were higher in Keros I and lower in Keros III (P <0.05). CONCLUSION In patients with lower LLCPA and OPCP, endoscopic sinus surgery will be more dangerous for trauma to lateral lamella and intracranial penetration.
Epidermal expression of human TRPM8, but not of TRPA1 ion channels, is associated with sensory responses to local skin cooling.

Human cold perception and nociception play an important role in persisting pain. However, species differences in the target temperature of thermosensitive ion channels expressed in peripheral nerve endings have fueled discussions about the mechanism of cold nociception in humans. Most frequently implicated thermosensors are members of the transient receptor potential (TRP) ion channel family TRPM8 and TRPA1. Regularly observed, distinct cold pain phenotype groups suggested the existence of inter-individually differing molecular bases. In 28 subjects displaying either high or medium sensitivity to local cooling of the skin, the density at epidermal nerve fibers of TRPM8, but not that of TRPA1 expression, correlated significantly with the cold pain threshold. Moreover, reproducible grouping of the subjects, based on high or medium sensitivity to cooling, was reflected in an analogous grouping based on high or low TRPM8 expression at epidermal nerve fibers. The distribution of TRPM8 expression in epidermal nerve fibers provided an explanation for the previously observed (bi)modal distribution of human cold pain thresholds which was reproduced in the present study. In the light of current controversies on the role of human TRPA1 ion channels in cold pain perception, the present observations demonstrating a lack of association of TRPA1 channel expression with cold sensitivity related measures reinforce doubts about involvement of this channel in cold pain in humans. Since TRP inhibitors targeting TRPM8 and TRPA1 are currently entering clinical phases of drug development, the existence of known species differences, in particular in the function of TRPA1, emphasize the increasing importance of new methods to directly approach the roles of TRPs in humans.
Low frataxin mRNA expression is associated with inflammation and oxidative stress in patients with type 2 diabetes

The mitochondrial protein frataxin is involved in iron metabolism, as well as regulation of oxidative stress. To elucidate the association of frataxin with the pathophysiology of diabetes, we evaluated the mRNA levels of frataxin in leukocytes of patients with type 2 diabetes (T2D). In addition, we investigated the relation between frataxin mRNA levels, inflammatory cytokines, and oxidative stress biomarkers.
Emerging Roles of RAD52 in Genome Maintenance

The maintenance of genome integrity is critical for cell survival. Homologous recombination (HR) is considered the major error-free repair pathway in combatting endogenously generated double-stranded lesions in DNA. Nevertheless, a number of alternative repair pathways have been described as protectors of genome stability, especially in HR-deficient cells. One of the factors that appears to have a role in many of these pathways is human RAD52, a DNA repair protein that was previously considered to be dispensable due to a lack of an observable phenotype in knock-out mice. In later studies, RAD52 deficiency has been shown to be synthetically lethal with defects in BRCA genes, making RAD52 an attractive therapeutic target, particularly in the context of BRCA-deficient tumors.
Antimicrobial resistance trends in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis urinary isolates from Switzerland: retrospective analysis of data from a national surveillance network over an 8-year period (2009-2016).

OBJECTIVES: Most urinary tract infections (UTIs) are treated empirically with antibiotics, making comprehensive resistance surveillance data essential to guide empiric regimens. We describe trends in the antibiotic resistance of urinary Enterobacteriaceae isolates in Switzerland between 2009 and 2016. METHODS We analysed data from routinely collected Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis urinary samples from community and hospital settings in Switzerland. The data were collected by ANRESIS, the national laboratory-based antimicrobial resistance surveillance system. Our analyses focused on resistance to antibiotics commonly prescribed for UTIs for the period 2009–2016. Only the first isolate per patient per year was included. RESULTS 297,200 urinary samples were included in the analysis, of which 246,656 (83.0%) were E. coli isolates. Overall, E. coli showed high susceptibility to 3rd/4th-generation cephalosporins, nitrofurantoin and fosfomycin, with the annual proportions of resistant isolates <6%, <5% and <2%, respectively, for all study years. Resistance to fluoroquinolones was >14% and increased over time (from 14.5% in 2009 to 19.3% in 2016). Resistance to cotrimoxazole was >20% for the whole study period. K. pneumoniae (n = 32,757; 11.0%) showed low resistance to cotrimoxazole and quinolones (<11% and <12%, respectively), while for P. mirabilis (n = 17,787; 6.0%) the proportion of resistant isolates was <35% for cotrimoxazole and <18% for quinolones. Even though quinolone resistance remained low for both pathogens (<12% for K. pneumoniae and <18% for P. mirabilis), it increased significantly over time. Proportions of isolates resistant to 3rd/4th generation cephalosporins remained low (<5% for K. pneumoniae and <2% for P. mirabilis), but in the case of K. pneumoniae they increased over time. CONCLUSIONS Swiss surveillance data confirm that resistance among uropathogenic E. coli isolates to nitrofurantoin and fosfomycin remains low. While resistance to 3rd/4th-generation cephalosporins also remains relatively low, it has been increasing and needs further surveillance. As for K. pneumoniae and P. mirabilis, high levels of susceptibility to 3rd-generation cephalosporins and quinolones were confirmed, while high prevalences of resistance to nitrofurantoin and fosfomycin discourage their use as first-line therapies for these pathogens.
A Real-Time Automated Patient Screening System for Clinical Trials Eligibility in an Emergency Department: Design and Evaluation

Background One critical hurdle for clinical trial recruitment is the lack of an efficient method for identifying subjects who meet the eligibility criteria. Given the large volume of data documented in electronic health records (EHRs), it is labor-intensive for the staff to screen relevant information, particularly within the time frame needed. To facilitate subject identification, we developed a natural language processing (NLP) and machine learning–based system, Automated Clinical Trial Eligibility Screener (ACTES), which analyzes structured data and unstructured narratives automatically to determine patients’ suitability for clinical trial enrollment. In this study, we integrated the ACTES into clinical practice to support real-time patient screening. Objective This study aimed to evaluate ACTES’s impact on the institutional workflow, prospectively and comprehensively. We hypothesized that compared with the manual screening process, using EHR-based automated screening would improve efficiency of patient identification, streamline patient recruitment workflow, and increase enrollment in clinical trials. Methods The ACTES was fully integrated into the clinical research coordinators’ (CRC) workflow in the pediatric emergency department (ED) at Cincinnati Children’s Hospital Medical Center. The system continuously analyzed EHR information for current ED patients and recommended potential candidates for clinical trials. Relevant patient eligibility information was presented in real time on a dashboard available to CRCs to facilitate their recruitment. To assess the system’s effectiveness, we performed a multidimensional, prospective evaluation for a 12-month period, including a time-and-motion study, quantitative assessments of enrollment, and postevaluation usability surveys collected from the CRCs. Results Compared with manual screening, the use of ACTES reduced the patient screening time by 34% (P<.001). The saved time was redirected to other activities such as study-related administrative tasks (P=.03) and work-related conversations (P=.006) that streamlined teamwork among the CRCs. The quantitative assessments showed that automated screening improved the numbers of subjects screened, approached, and enrolled by 14.7%, 11.1%, and 11.1%, respectively, suggesting the potential of ACTES in streamlining recruitment workflow. Finally, the ACTES achieved a system usability scale of 80.0 in the postevaluation surveys, suggesting that it was a good computerized solution. Conclusions By leveraging NLP and machine learning technologies, the ACTES demonstrated good capacity for improving efficiency of patient identification. The quantitative assessments demonstrated the potential of ACTES in streamlining recruitment workflow and improving patient enrollment. The postevaluation surveys suggested that the system was a good computerized solution with satisfactory usability.
Total and Regional Body Composition of NCAA Division I Collegiate Female Softball Athletes

Abstract The purpose of this study was to evaluate total, regional, and throwing versus non-throwing arm body composition measures across the 4 major positions of NCAA Division I female softball players using dual X-ray absorptiometry (DXA) (n=128). Total and regional total mass (TM), fat mass (FM), lean mass (LM), bone mineral density (BMD), bone mineral content (BMC), and visceral adipose tissue were measured. Athletes were separated into: pitchers (n=32), catchers (n=13), outfielders (n=39), and infielders (n=44). ANOVA and Tukey’s HSD assessed total and regional differences between positions. Although no significant total or regional LM differences were observed across positions, outfielders had significantly (p=0.006–0.047) lower total-body, arm, and trunk TM and FM, leg FM, and leg BMC in comparison to pitchers. The throwing arm had significantly (p<0.0001–0.018) greater LM, BMD, and BMC than the non-throwing arm for all positions. Notably, there were minimal body composition differences among softball positions, with the primary differences being that pitchers had larger total and regional fat values than outfielders. The throwing arm of all positions had greater LM, BMD, and BMC than the non-throwing arm. These values can be used by coaches and trainers as descriptive DXA data for collegiate softball players.
The Passive Mechanical Properties of Muscles and Tendons in Children Affected by Osgood-Schlatter Disease

Background: Osgood-Schlatter disease (OSD) is a sports-related disorder involving apophysitis, which affects the tibial tuberosity. The identification of factors related to OSD is important for its prevention and early recovery from the disease. This study aimed to compare the passive mechanical properties of the muscle-tendon unit in children affected by an OSD and healthy children, by using ultrasound real-time tissue elastography. Methods: Eighteen legs affected by OSD (OSD group) and 42 healthy legs (control: CON group) were assessed. The elasticity was obtained from the quadriceps muscles and patella tendon (PT) using real-time tissue elastography. The strain ratio (SR; muscle or tendon/reference ratio: strain rate of the muscle or tendon divided by that of the reference material) was calculated as an indicator of the elasticity of the tissue of interest. Results: The SR of the PT in the OSD group was significantly lower than that in the CON group (P<0.05). We found no significant difference between the groups in terms of the SR value of all muscles (P>0.05). Conclusions: The results suggest that a PT with a lower SR may be associated with an OSD and that the passive mechanical properties of the quadriceps muscles have limited association with an OSD. Levels of Evidence: Level IV.
The Effect of Reflective Teaching Practice on Iranian EFL Learners’ Complexity, Accuracy and Fluency of Oral Speech

Reflection is a professional development strategy that equips language teachers with opportunities to explore, articulate and represent their own teaching practices. This research was conducted to evaluate the impact of English teachers’ reflection on EFL learners’ speaking proficiency as measured in terms of accuracy, fluency and complexity. Employing a quasi-experimental design, the researchers collected the required quantitative data through the audio recording of interviews conducted with the participants in the study and through a measure of teacher reflection. Sixty students (30 males and 30 females) and thirty instructors (15 males and 15 females) were randomly selected from English institutes in Bandar Abbas as the sample of the study. The results revealed that teachers’ reflectivity significantly affects Iranian EFL learners’ oral performance in terms of fluency and learners’ syntactic complexity of oral speech but it was found that those instructed by the high reflective teacher did not show any progress in accuracy of oral speech.
Timing of evidence-based psychotherapy for posttraumatic stress disorder initiation among Iraq and Afghanistan war veterans in the Veterans Health Administration.

OBJECTIVE Cognitive processing therapy (CPT) and prolonged exposure therapy (PE) were widely disseminated to treat posttraumatic stress disorder (PTSD) in the Veterans Health Administration (VHA). However, few Iraq and Afghanistan war veterans (Operation Enduring Freedom [OEF], Operation Iraqi Freedom [OIF], Operation New Dawn [OND]) diagnosed with PTSD have received CPT/PE and many initiate CPT/PE after substantial delay. Veterans who do not initiate CPT/PE or initiate CPT/PE after delay may have poorer treatment outcomes. This study aimed to identify predictors of CPT/PE initiation and timing. METHODS Participants included OEF/OIF/OND veterans diagnosed with PTSD who received psychotherapy between 2001 and 2017 in the VHA (n = 265,566). Logistic regression analysis was utilized to predict initiating CPT/PE (vs. no CPT/PE). Multinomial logistic regression analysis was utilized to predict not initiating or initiating delayed CPT/PE versus "early CPT/PE" (< 1 year after first mental health visit). Analyzed predictors included demographic, military, and clinical complexity variables (e.g., comorbidities, reported military sexual trauma [MST] history). RESULTS Seventy-Seven percent of veterans did not initiate CPT/PE, with 7.4% initiating early and 15.4% initiating delayed CPT/PE. Reported MST history (odds ratio [OR] = 1.45, 95% CI [1.39, 1.51]) and history of suicidal ideation/attempt (OR = 1.42, 95% CI [1.38, 1.46]) were strong predictors of CPT/PE initiation versus no CPT/PE. Comorbid pain (relative risk ratio [RRR] = 1.35, 95% CI [1.30, 1.42]) and depressive disorders (RRR = 1.37, 95% CI [1.32, 1.43]) were associated with increased likelihood of delayed versus early CPT/PE. CONCLUSIONS Most veterans in our study did not initiate CPT/PE. Generally, clinical complexity variables increased likelihood of initiating CPT/PE and initiating CPT/PE more than 1 year after first mental health visit. Additional research is needed to understand whether CPT/PE delay results from receipt of alternative intervention due to clinical complexity variables. (PsycINFO Database Record (c) 2019 APA, all rights reserved).