Miracle-dz/UniFAR-FTUs huggingface dataset:
Active membrane conductances and morphology of a collision detection neuron broaden its impedance profile and improve discrimination of input synchrony.

How neurons filter and integrate their complex patterns of synaptic inputs is central to their role in neural information processing . Synaptic filtering and integration are shaped by the frequency-dependent neuronal membrane impedance. Using single and dual dendritic recordings in vivo, pharmacology, and computational modeling, we characterized the membrane impedance of a collision detection neuron in the grasshopper, Schistocerca americana. This neuron, the lobula giant movement detector (LGMD), exhibits consistent impedance properties across frequencies and membrane potentials. Two common active conductances gH and gM, mediated respectively by hyperpolarization-activated cyclic nucleotide gated (HCN) channels and by muscarine sensitive M-type K+ channels, promote broadband integration with high temporal precision over the LGMD's natural range of membrane potentials and synaptic input frequencies. Additionally, we found that a model based on the LGMD's branching morphology increased the gain and decreased the delay associated with the mapping of synaptic input currents to membrane potential. More generally, this was true for a wide range of model neuron morphologies, including those of neocortical pyramidal neurons and cerebellar Purkinje cells. These findings show the unexpected role played by two widespread active conductances and by dendritic morphology in shaping synaptic integration.
Rural-urban disparities in smoking patterns among Chinese adults: a social-ecological approach

Abstract China has a long history of smoking behavior. Currently, nearly 26% of Chinese citizens smoke daily. This research used a nationally representative database to study the urban and rural disparities on smoking patterns applying the social-ecological model. Using the 2011 China Health and Nutrition Survey, the study sample included adult participants who were at least 18 years of age (n = 12,688). A subanalysis was carried out to investigate smoking cessation duration among smoking quitters (n = 519). Multinomial logistic regression was used to examine participants' smoking status. Zero-inflated negative binomial regression was applied to investigate participants' number of cigarettes smoked per day, and multivariable logistic regression was used to examine nondaily smoking behavior. Negative binomial regression was carried out to assess the duration of smoking cessation for individuals who quit smoking. Urban residents had lower odds of reporting current smoking status (AOR [adjusted odds ratio] = 0.83, 95% CI [0.74, 0.95]) as compared to rural residents. Urban residents also had higher odds of reporting nondaily smoking status (AOR = 1.17, 95% CI [1.04, 1.32]) and smoked fewer cigarettes per day (IRR [incidence rate ratio] = 0.93, 95% CI [0.89, 0.98]) as compared to rural participants. The disparity between urban and rural areas was not observed for smoking cessation duration. Further efforts should target the disparity between urban and rural regions regarding smoking prevention.
Evaluation of auto‐planning in IMRT and VMAT for head and neck cancer

Abstract Purpose The purposes of this work are to (a) investigate whether the use of auto‐planning and multiple iterations improves quality of head and neck (HN) radiotherapy plans; (b) determine whether delivery methods such as step‐and‐shoot (SS) and volumetric modulated arc therapy (VMAT) impact plan quality; (c) report on the observations of plan quality predictions of a commercial feasibility tool. Materials and methods Twenty HN cases were retrospectively selected from our clinical database for this study. The first ten plans were used to test setting up planning goals and other optimization parameters in the auto‐planning module. Subsequently, the other ten plans were replanned with auto‐planning using step‐and‐shoot (AP‐SS) and VMAT (AP‐VMAT) delivery methods. Dosimetric endpoints were compared between the clinical plans and the corresponding AP‐SS and AP‐VMAT plans. Finally, predicted dosimetric endpoints from a commercial program were assessed. Results All AP‐SS and AP‐VMAT plans met the clinical dose constraints. With auto‐planning, the dose coverage of the low dose planning target volume (PTV) was improved while the dose coverage of the high dose PTV was maintained. Compared to the clinical plans, the doses to critical organs, such as the brainstem, parotid, larynx, esophagus, and oral cavity were significantly reduced in the AP‐VMAT (P < 0.05); the AP‐SS plans had similar homogeneity indices (HI) and conformality indices (CI) and the AP‐VMAT plans had comparable HI and improved CI. Good agreement in dosimetric endpoints between predictions and AP‐VMAT plans were observed in five of seven critical organs. Conclusion With improved planning quality and efficiency, auto‐planning module is an effective tool to enable planners to generate HN IMRT plans that are meeting institution specific planning protocols. DVH prediction is feasible in improving workflow and plan quality.
Coxsackievirus-B4 Infection of Human Primary Pancreatic Ductal Cell Cultures Results in Impairment of Differentiation into Insulin-Producing Cells

Coxsackievirus-B4 (CV-B4) E2 can persist in the pancreatic ductal-like cells (Panc-1 cell line), which results in an impaired differentiation of these cells into islet-like cell aggregates (ICA). In this study, primary pancreatic ductal cells obtained as a by-product of islet isolation from the pancreas of seven brain-dead adults were inoculated with CV-B4 E2, followed-up for 29 days, and the impact was investigated. Viral titers in culture supernatants were analyzed throughout the culture. Intracellular viral RNA was detected by RT-PCR. Levels of ductal cell marker CK19 mRNA and of insulin mRNA were evaluated by qRT-PCR. The concentration of c-peptide in supernatants was determined by ELISA. Ductal cells exposed to trypsin and serum-free medium formed ICA and resulted in an increased insulin secretion. Ductal cells from five brain-dead donors were severely damaged by CV-B4 E2, whereas the virus persisted in cultures of cells obtained from the other two. The ICAs whose formation was induced on day 14 post-inoculation were scarce and appeared tiny in infected cultures. Also, insulin mRNA expression and c-peptide levels were strongly reduced compared to the controls. In conclusion, CV-B4 E2 lysed human primary pancreatic ductal cells or persisted in these cells, which resulted in the impairment of differentiation into insulin-producing cells.
Is it just me, or was that sexist? The role of sexism type and perpetrator race in identifying sexism

ABSTRACT Despite sexism occurring frequently, people often do not identify it as such. Using a vignette design, the current project explored whether sexism was identified at a different rate and intensity depending on the specific form of sexism enacted (hostile or benevolently sexist behavior) and race (Black or White) of the man perpetrating sexist behaviors. When a Black man engaged in a benevolently (paternalistic) sexist behavior he was perceived as more sexist than a White man. However, White and Black men were perceived similarly when they engaged in a hostile (overtly negative and derogatory) sexist behavior. Overall, female participants identified sexism more often and viewed it as more sexist than male participants did, especially in the context of benevolent sexism. These findings suggest there are significant effects of perceiver gender and perpetrator race in the perception of sexism. This demonstrates the importance of examining both race- and gender-based discrimination together.
Oral Phenelzine Treatment Mitigates Metabolic Disturbances in Mice Fed a High-Fat Diet

Novel mechanisms and health benefits have been recently suggested for the antidepressant drug phenelzine (PHE), known as a nonselective monoamine oxidase inhibitor. They include an antilipogenic action that could have an impact on excessive fat accumulation and obesity-related metabolic alterations. We evaluated the metabolic effects of an oral PHE treatment on mice fed a high-fat diet (HFD). Eleven-week-old male C57BL/6 mice were fed a HFD and either a 0.028% PHE solution (HFD + PHE) or water to drink for 11 weeks. PHE attenuated the increase in body weight and adiposity without affecting food consumption. Energy efficiency was lower in HFD + PHE mice. Lipid content was reduced in subcutaneous fat pads, liver, and skeletal muscle. In white adipose tissue (WAT), PHE reduced sterol regulatory element-binding protein-1c and phosphoenolpyruvate carboxykinase mRNA levels, inhibited amine-induced lipogenesis, and did not increase lipolysis. Moreover, HFD + PHE mice presented diminished levels of hydrogen peroxide release in subcutaneous WAT and reduced expression of leukocyte transmigration markers and proinflammatory cytokines in visceral WAT and liver. PHE reduced the circulating levels of glycerol, triacylglycerols, high-density lipoprotein cholesterol, and insulin. Insulin resistance was reduced, without affecting glucose levels and glucose tolerance. In contrast, PHE increased rectal temperature and slightly increased energy expenditure. The mitigation of HFD-induced metabolic disturbances points toward a promising role for PHE in obesity treatment and encourages further research on its mechanisms of action. SIGNIFICANCE STATEMENT Phenelzine reduces body fat, markers of oxidative stress, inflammation, and insulin resistance in high-fat diet mice. Semicarbazide-sensitive amine oxidase, monoamine oxidase, phosphoenolpyruvate carboxykinase, and sterol regulatory element-binding protein-1c are involved in the metabolic effects of phenelzine. Phenelzine could be potentially used for the treatment of obesity-related complications.
Adolescent stress increases depression-like behaviors and alters the excitatory-inhibitory balance in aged mice

Abstract Background: Depression affects approximately 5% of elderly people and its etiology might be related to chronic stress exposure during neurodevelopmental periods. In this study, we examined the effects of adolescent chronic social stress in aged mice on depressive behaviors and the excitatory-inhibitory (E/I) balance in stress-sensitive regions of the brain. Methods: Sixty-four adolescent, male C57BL/6 mice were randomly assigned to either the 7-week (from post-natal days 29 to 77) social instability stress (stress group, n = 32) or normal housing conditions (control group, n = 32). At 15 months of age, 16 mice were randomly selected from each group for a series of behavioral tests, including two depression-related tasks (the sucrose preference test and the tail suspension test). Three days following the last behavioral test, eight mice were randomly selected from each group for immunohistochemical analyses to measure the cell density of parvalbumin (PV+)- and calretinin (CR+)-positive gamma-aminobutyric-acid (GABA)ergic inhibitory inter-neurons, and the expression levels of vesicular transporters of glutamate-1 (VGluT1) and vesicular GABA transporter (VGAT) in three stress-sensitive regions of the brain (the medial pre-frontal cortex [mPFC], hippocampus, and amygdala). Results: Behaviorally, compared with the control group, adolescent chronic stress increased depression-like behaviors as shown in decreased sucrose preference (54.96 ± 1.97% vs. 43.11 ± 2.85%, t(22) = 3.417, P = 0.003) and reduced latency to immobility in the tail suspension test (92.77 ± 25.08 s vs. 33.14 ± 5.95 s, t(25) = 2.394, P = 0.025), but did not affect anxiety-like behaviors and pre-pulse inhibition. At the neurobiologic level, adolescent stress down-regulated PV+, not CR+, inter-neuron density in the mPFC (F(1, 39) = 19.30, P < 0.001), and hippocampus (F(1, 42) = 5.823, P = 0.020) and altered the CR+, not PV+, inter-neuron density in the amygdala (F(1, 28) = 23.16, P < 0.001). The VGluT1/VGAT ratio was decreased in all three regions (all F > 10.09, all P < 0.004), which suggests stress-induced hypoexcitability in these regions. Conclusions: Chronic stress during adolescence increased depression-like behaviors in aged mice, which may be associated with the E/I imbalance in stress-sensitive brain regions.
Noise-reducing optogenetic negative-feedback gene circuits in human cells

Abstract Gene autorepression is widely present in nature and is also employed in synthetic biology, partly to reduce gene expression noise in cells. Optogenetic systems have recently been developed for controlling gene expression levels in mammalian cells, but most have utilized activator-based proteins, neglecting negative feedback except for in silico control. Here, we engineer optogenetic gene circuits into mammalian cells to achieve noise-reduction for precise gene expression control by genetic, in vitro negative feedback. We build a toolset of these noise-reducing Light-Inducible Tuner (LITer) gene circuits using the TetR repressor fused with a Tet-inhibiting peptide (TIP) or a degradation tag through the light-sensitive LOV2 protein domain. These LITers provide a range of nearly 4-fold gene expression control and up to 5-fold noise reduction from existing optogenetic systems. Moreover, we use the LITer gene circuit architecture to control gene expression of the cancer oncogene KRAS(G12V) and study its downstream effects through phospho-ERK levels and cellular proliferation. Overall, these novel LITer optogenetic platforms should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology and other biomedical fields of research.
Dual-energy material decomposition for cone-beam computed tomography in image-guided radiotherapy

Abstract Background: Dual-energy (DE) diagnostic computed tomography (CT) combines two scans of different photon energy spectra which can provide additional image information as compared to standard CT. We developed a DE material decomposition scan protocol for daily cone-beam CT (CBCT) of head-and-neck patients receiving radiotherapy and tested it in a clinical trial. Material and methods: Our DE CBCT protocol consisted of an 80 and 140 kVp scan. The material decomposition algorithm split the low and high energy scan into components of two basis materials, aluminum and acrylic. Scans of different thicknesses and overlap of the basis materials were acquired to calibrate the model which decomposed the CBCT projections into thicknesses of aluminum and acrylic on a per-pixel basis. Pseudo monochromatic projections were created from these thicknesses and the known energy dependence of the attenuation coefficient of the basis materials. A frequency selective de-noising method was further applied to the basis material projections. The DE CBCT protocol was tested on seven patients. Two DE images were chosen, one at low (50–60) keV to evaluate soft tissue image quality and one at 150 keV to assess metal artifact reduction as compared to standard CBCT. Results: The de-noising algorithm reduced noise by 41% and 69% in the 60 and 150 keV images, respectively, compared to images without the de-noising. The low keV image showed an increase in soft tissue contrast-to-noise ratio of 7–43% compared to the standard clinical CBCT for six of the seven patients. The 150 keV DE CBCT image reduced metal artifacts. Enhanced streaking from metal artifacts were observed in some of the DE CBCT images. Conclusion: Monochromatic DE images from material decomposition can improve soft tissue contrast-to-noise ratio and metal artifact reduction. Improvements are limited, however, and new artifacts were also introduced by the DE algorithm.
Language boosting by transcranial stimulation in progressive supranuclear palsy

Objective To explore whether transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) can improve language capacities in patients with progressive supranuclear palsy (PSP). Methods We used a sham-controlled double-blind crossover design to assess the efficiency of tDCS over the DLPFC in a cohort of 12 patients with PSP. In 3 separate sessions, we evaluated the ability to boost the left DLPFC via left-anodal (excitatory) and right-cathodal (inhibitory) tDCS, while comparing them to sham tDCS. Tasks assessing lexical access (letter fluency task) and semantic access (category judgment task) were applied immediately before and after the tDCS sessions to provide a marker of potential language modulation. Results The comparison with healthy controls showed that patients with PSP were impaired on both tasks at baseline. Contrasting poststimulation vs prestimulation performance across tDCS conditions revealed language improvement in the category judgment task following right-cathodal tDCS, and in the letter fluency task following left-anodal tDCS. A computational finite element model of current distribution corroborated the intended effect of left-anodal and right-cathodal tDCS on the targeted DLPFC. Conclusions Our results demonstrate tDCS-driven language improvement in PSP. They provide proof-of-concept for the use of tDCS in PSP and set the stage for future multiday stimulation regimens, which might lead to longer-lasting therapeutic effects promoted by neuroplasticity. Classification of evidence This study provides Class III evidence that for patients with PSP, tDCS over the DLPFC improves performance in some language tasks.
Pediatric Pulmonology

Correspondece Athanasios Kaditis, MD, First Department of Pediatrics, Aghia Sophia Childrenʼs Hospital, Thivon and Papadiamantopoulou St., Athens 11527, Greece. Email: kaditia@hotmail.com Abstract Objective: To assess whether children with sleep‐disordered breathing (SDB) symptom severity above a certain level, measured by a validated questionnaire, improve after adenotonsillectomy (AT) compared to no intervention. Methods: Children with snoring and tonsillar hypertrophy (4 to 10‐years old), who were candidates for AT, were randomly assigned to two evaluation sequences (baseline and 3‐month follow‐up): (a) evaluation immediately before AT and at 3 months postoperatively (AT group); or (b) evaluation at the initial visit and at the end of the usual 3‐month waiting period for surgery (control group). Outcomes were (a) Pediatric Sleep Questionnaire sleep‐related breathing disorder scale (PSQ‐SRBD); (b) modified Epworth Sleepiness Scale (mESS); and (c) proportion of subjects achieving PSQ‐SRBD <0.33 (low‐risk for apnea‐hypopnea index ≥5/h) if they had score ≥0.33 at baseline. Results: Sixty‐eight children were assigned to the AT and 72 to the control group and two‐thirds of them had PSQ‐SRBD ≥0.33. The AT group experienced significantly larger improvement between follow‐up and baseline than controls (between‐group difference [95% CI] for PSQ‐SRBD: −0.31 [−0.35 to −0.27]; and mESS: −2.76 [−3.63 to −1.90]; P < .001 for both). Children with baseline PSQ‐SRBD ≥0.33 in the AT group had an eight‐times higher probability of achieving PSQ‐SRBD <0.33 at follow‐up than controls with similar baseline score (risk ratio [95% CI]: 8.33 [3.92‐17.54]; P < .001). Conclusion: Among children with snoring, tonsillar hypertrophy, and clinical indications for AT, those with preoperative PSQ‐SRBD score ≥0.33 show measurable clinical benefit postoperatively.
Heterogeneous antiretroviral drug distribution and HIV/SHIV detection in the gut of three species

Imaging reveals that antiretroviral drugs are not distributed evenly in the mammalian gut, with potential implications for HIV replication. Hidden in Plain Sight Insufficient exposure of tissues harboring residual HIV, including the gut, to antiretroviral drugs may contribute to HIV persistence. Thompson et al. now apply a mass spectrometry–based imaging technique to visualize the distribution of six antiretroviral drugs in gut tissue sections from two animal species (mice and macaques) and HIV-infected patients. The authors found that drug distribution was uneven throughout the gut tissue. They also found that a major proportion of gut T cells, which are targeted by HIV, did not colocalize with an antiretroviral drug. In addition, viral RNA could still be detected during drug treatment, particularly in areas of low antiretroviral drug concentrations, potentially contributing to ongoing viral replication. HIV replication within tissues may increase in response to a reduced exposure to antiretroviral drugs. Traditional approaches to measuring drug concentrations in tissues are unable to characterize a heterogeneous drug distribution. Here, we used mass spectrometry imaging (MSI) to visualize the distribution of six HIV antiretroviral drugs in gut tissue sections from three species (two strains of humanized mice, macaques, and humans). We measured drug concentrations in proximity to CD3+ T cells that are targeted by HIV, as well as expression of HIV or SHIV RNA and expression of the MDR1 drug efflux transporter in gut tissue from HIV-infected humanized mice, SHIV-infected macaques, and HIV-infected humans treated with combination antiretroviral drug therapy. Serial 10-μm sections of snap-frozen ileal and rectal tissue were analyzed by MSI for CD3+ T cells and MDR1 efflux transporter expression by immunofluorescence and immunohistochemistry, respectively. The tissue slices were analyzed for HIV/SHIV RNA expression by in situ hybridization and for antiretroviral drug concentrations by liquid chromatography–mass spectrometry. The gastrointestinal tissue distribution of the six drugs was heterogeneous. Fifty percent to 60% of CD3+ T cells did not colocalize with detectable drug concentrations in the gut tissue. In all three species, up to 90% of HIV/SHIV RNA was found to be expressed in gut tissue with no exposure to drug. These data suggest that there may be gut regions with little to no exposure to antiretroviral drugs, which may result in low-level HIV replication contributing to HIV persistence.
Efficacy of vibrotactile device DentalVibe in reducing injection pain and anxiety during local anaesthesia in paediatric dental patients: a study protocol for a randomised controlled clinical trial

Introduction A current non-pharmacological mean for attaining painless local anaesthesia (LA) is presented by vibrotactile devices. Their concept is to reduce injection pain due to distraction by applying physical stimuli which interfere with pain signals. The aim of this study is to determine the efficacy of the DentalVibe (DV) device in reducing pain and anxiety associated with LA in paediatric patients. Methods and analysis The proposed study is a randomised controlled clinical trial with split-mouth design. Included are positive patients aged 8–12 years, requiring buccal infiltration for extraction of two bilateral primary maxillary molars. After dental fear measurement, eligible patients undergo two single-visit treatments with DV device allocated to either first or second LA via computer-generated randomisation sequence. Outcome measures will be self-reported pain felt during LA on Visual Analogue Scale; self-reported anxiety on Facial Image Scale; pain-related behaviour according to Faces, Legs, Activity, Cry, Consolability Scale; heart rate; patient preference to LA technique. Data will be analysed with intention-to-treat concept by Student’s t-test for paired samples, Wilcoxon signed-rank test, p<0.05. Pretest on 20 subjects resulted in n=41 patients sample size. Ethics and dissemination This study protocol has been approved by the Committee for Scientific Research Ethics, Medical University - Plovdiv, Bulgaria (Reference number P-8604, Protocol of approval No. 6/23.11.2017) and registered on a publicly accessible database. This research received institutional funding from the Medical University - Plovdiv, Bulgaria, under project SPD-03/2017. Findings will be reported in scientific publications and at research conferences, and in project summary papers for participants. Trial registration number NCT03445182; Pre-results.