Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA Repair and Transcriptional Deficiencies Caused by Mutations in the Drosophila p52 Subunit of TFIIH Generate Developmental Defects and Chromosome Fragility

ABSTRACT The transcription and DNA repair factor TFIIH is composed of 10 subunits. Mutations in the XPB, XPD, and p8 subunits are genetically linked to human diseases, including cancer. However, no reports of mutations in other TFIIH subunits have been reported in higher eukaryotes. Here, we analyze at genetic, molecular, and biochemical levels the Drosophila melanogaster p52 (DMP52) subunit of TFIIH. We found that DMP52 is encoded by the gene marionette in Drosophila and that a defective DMP52 produces UV light-sensitive flies and specific phenotypes during development: organisms are smaller than their wild-type siblings and present tumors and chromosomal instability. The human homologue of DMP52 partially rescues some of these phenotypes. Some of the defects observed in the fly caused by mutations in DMP52 generate trichothiodystrophy and cancer-like phenotypes. Biochemical analysis of DMP52 point mutations introduced in human p52 at positions homologous to those of defects in DMP52 destabilize the interaction between p52 and XPB, another TFIIH subunit, thus compromising the assembly of the complex. This study significantly extends the role of p52 in regulating XPB ATPase activity and, consequently, both its transcriptional and nucleotide excision repair functions.
Utility of serial computed tomography imaging in pediatric patients with head trauma.

OBJECT The purpose of this study was to evaluate the risk of progression of traumatic intracranial lesions in children by comparing initial and subsequent computed tomography (CT) scans. Reserving repeated CT imaging for patients who harbor higher-risk lesions may reduce overall radiation exposure, the need for sedative agents, and cost. METHODS The authors performed a retrospective cohort study in 268 patients younger than 18 years of age who underwent repeated CT scanning within 24 hours of their initial CT scanning procedure. The risk of progression between the initial and repeated CT scanning sessions and the need for delayed neurosurgical intervention were determined for each lesion type. In 54 patients (20.1%) the normal findings on the initial CT study did not change on subsequent imaging. In 61 (28.5%) of the 214 patients in whom abnormal findings were present on the initial scan, progression was demonstrated. Patients with epidural hematoma (EDH; odds ratio [OR] 12.29), subdural hematoma (SDH; OR 3.18), cerebral edema (OR 9.34), and intraparenchymal hemorrhage (IPH; OR 18.3) were found to be at a significantly increased risk for progression and to require delayed neurosurgical intervention (OR 11.91). No significantly increased risk was found for patients with subarachnoid hemorrhage (SAH), intraventricular hemorrhage (IVH), diffuse axonal injury (DAI), or skull fracture. CONCLUSIONS Repeated CT imaging in children with high-risk lesions such as EDH, SDH, cerebral edema, and IPH is recommended. However, in children with low-risk lesions, such as SAH, IVH, DAI, and isolated skull fractures but no sign of clinical deterioration, repeated imaging may be less likely to alter the clinical management scheme. The limited benefits of undertaking repeated imaging in these patients should be weighed against the risks of radiation exposure, sedation, intrahospital transportation, and patient monitoring.
Linear and nonlinear heart-rate analysis in a rat model of acute anoxia

The objective of this study was the assessment of heart-rate (HR) dynamics with linear and nonlinear methods during episodes of mechanical ventilation and acute anoxia in rats. Namely, to assess whether linear and nonlinear HR analysis was able to discriminate acute anoxia from baseline in rats and if this was consistent with human foetal and adult studies. Five HR segments of 1 min duration, during baseline recording, mechanical ventilation and first, second and third minutes of induced acute anoxia, were analysed in ten adult Wistar rats. Linear time and frequency domain and nonlinear methods were used, namely mean HR (mHR), long-term irregularity (LTI), interval index (II), low frequency (LF) and high frequency (HF), approximate entropy (ApEn) and sample entropy (SampEn). New parameters for the entropy indices are proposed for the analysis of rats' HR. Bootstrap percentile confidence intervals and nonparametric statistical tests were used in the evaluation of the differences between segments. During mechanical ventilation a clear spectral band was detectable at the ventilation rate, but mHR, II and the ‘new’ entropy indices were the only significantly changed indices. In the transition from baseline–mechanical-ventilation to mechanical-ventilation–induced anoxia, a statistically significant decrease of mHR, II and entropy indices was observed, clearly discriminating these two instances, whereas most linear indices increased. With continued anoxia, most linear indices decreased significantly, whereas entropy remained stably low. These results are consistent with other foetal human and non-human studies and evidence that the rat model may be used for further research on linear and nonlinear analysis of heart-rate dynamics. The transition from baseline to acute anoxia was encompassed by signs of increased activation of the autonomic nervous system sympathetic branch, and decreased or blunted activity of the HR complexity regulatory centres.
Clinical Impact of Tumor-Infiltrating Inflammatory Cells in Primary Small Cell Esophageal Carcinoma

Primary small cell esophageal carcinoma is a rare and aggressive type of gastrointestinal cancer with poor prognosis. In the present study, the impact of tumour infiltrating inflammatory cells on clinico-pathological characteristics and the patients’ prognosis were analysed. A total of 36 small cell esophageal carcinomas, 19 adjacent normal tissues and 16 esophageal squamous cell carcinoma samples were collected. Qualified pathologists examined eosinophils, neutrophils, lymphocytes and macrophages on histochemical slides. The infiltration of eosinophils and macrophages in small cell esophageal carcinoma was significantly increased as compared with tumor adjacent normal tissues, and was significantly less in esophageal squamous cell carcinoma. Macrophage count was significantly associated with (p = 0.015) lymph node—stage in small cell esophageal carcinoma. When we grouped patients into two groups by counts of infiltrated inflammatory cells, Kaplan-Meier analysis revealed that high macrophage infiltration group (p = 0.004) and high eosinophil infiltration group (p = 0.027) had significantly enhanced survival. In addition, multivariate analysis unveiled that eosinophil count (p = 0.002) and chemotherapy (Yes vs. No, p = 0.001) were independent prognostic indicators. Taken together, infiltration of macrophages and eosinophils into the solid tumor appear to be important in the progression of small cell esophageal carcinoma and patients’ prognosis.
Investigating the Role of Ocean-Atmosphere Coupling in the North Pacific Ocean

AbstractAir–sea interaction over the North Pacific is diagnosed using a simple, local coupled autoregressive model constructed from observed 7-day running-mean sea surface temperature (SST) and 2-m air temperature TA anomalies during the extended winter from the 1° × 1° objectively analyzed air–sea fluxes (OAFlux) dataset. Though the model is constructed from 1-week lag statistics, it successfully reproduces the observed anomaly evolution through lead times of 90 days, allowing an estimation of the relative roles of coupling and internal atmospheric and oceanic forcing upon North Pacific SSTs. It is found that east of the date line, SST variability is maintained by, but has little effect on, TA variability. However, in the Kuroshio–Oyashio confluence and extension region, about half of the SST variability is independent of TA, driven instead by SST noise forcing internal to the ocean. Including surface zonal winds in the analysis does not alter this conclusion, suggesting TA adequately represents the atmo.
Rod Microglia: A Morphological Definition

Brain microglial morphology relates to function, with ramified microglia surveying the micro-environment and amoeboid microglia engulfing debris. One subgroup of microglia, rod microglia, have been observed in a number of pathological conditions, however neither a function nor specific morphology has been defined. Historically, rod microglia have been described intermittently as cells with a sausage-shaped soma and long, thin processes, which align adjacent to neurons. More recently, our group has described rod microglia aligning end-to-end with one another to form trains adjacent to neuronal processes. Confusion in the literature regarding rod microglia arises from some reports referring to the sausage-shaped cell body, while ignoring the spatial distribution of processes. Here, we systematically define the morphological characteristics of rod microglia that form after diffuse brain injury in the rat, which differ morphologically from the spurious rod microglia found in uninjured sham. Rod microglia in the diffuse-injured rat brain show a ratio of 1.79±0.03 cell length∶cell width at day 1 post-injury, which increases to 3.35±0.05 at day 7, compared to sham (1.17±0.02). The soma length∶width differs only at day 7 post-injury (2.92±0.07 length∶width), compared to sham (2.49±0.05). Further analysis indicated that rod microglia may not elongate in cell length but rather narrow in cell width, and retract planar (side) processes. These morphological characteristics serve as a tool for distinguishing rod microglia from other morphologies. The function of rod microglia remains enigmatic; based on morphology we propose origins and functions for rod microglia after acute neurological insult, which may provide biomarkers or therapeutic targets.
Stable association of chloroplastic precursors with protein translocation complexes that contain proteins from both envelope membranes and a stromal Hsp100 molecular chaperone

Cytoplasmically synthesized precursors interact with translocation components in both the outer and inner envelope membranes during transport into chloroplasts. Using co‐immunoprecipitation techniques, with antibodies specific to known translocation components, we identified stable interactions between precursor proteins and their associated membrane translocation components in detergent‐solubilized chloroplastic membrane fractions. Antibodies specific to the outer envelope translocation components OEP75 and OEP34, the inner envelope translocation component IEP110 and the stromal Hsp100, ClpC, specifically co‐immunoprecipitated precursor proteins under limiting ATP conditions, a stage we have called docking. A portion of these same translocation components was co‐immunoprecipitated as a complex, and could also be detected by co‐sedimentation through a sucrose density gradient. ClpC was observed only in complexes with those precursors utilizing the general import apparatus, and its interaction with precursor‐containing translocation complexes was destabilized by ATP. Finally, ClpC was co‐immunoprecipitated with a portion of the translocation components of both outer and inner envelope membranes, even in the absence of added precursors. We discuss possible roles for stromal Hsp100 in protein import and mechanisms of precursor binding in chloroplasts.
Mps1 Phosphorylation Sites Regulate the Function of Centrin 2 in Centriole Assembly

We show that while Centrin2 is dispensable for centriole assembly, it is an Mps1 substrate that stimulates canonical and aberrant centriole assembly by two different Mps1-dependent mechanisms, HsSas-6–dependent and –independent. Centrin2 phosphorylation is also required for the ability of Mps1 to drive production of mature centrioles.
Increased Cortical Thickness in Professional On-Line Gamers

Objective The bulk of recent studies have tested whether video games change the brain in terms of activity and cortical volume. However, such studies are limited by several factors including cross-sectional comparisons, co-morbidity, and short-term follow-up periods. In the present study, we hypothesized that cognitive flexibility and the volume of brain cortex would be correlated with the career length of on-line pro-gamers. Methods High-resolution magnetic resonance scans were acquired in twenty-three pro-gamers recruited from StarCraft pro-game teams. We measured cortical thickness in each individual using FreeSurfer and the cortical thickness was correlated with the career length and the performance of the pro-gamers. Results Career length was positively correlated with cortical thickness in three brain regions: right superior frontal gyrus, right superior parietal gyrus, and right precentral gyrus. Additionally, increased cortical thickness in the prefrontal cortex was correlated with winning rates of the pro-game league. Increased cortical thickness in the prefrontal and parietal cortices was also associated with higher performance of Wisconsin Card Sorting Test. Conclusion Our results suggest that in individuals without pathologic conditions, regular, long-term playing of on-line games is associated with volume changes in the prefrontal and parietal cortices, which are associated with cognitive flexibility.
Responses of plasma adrenocortical steroids to low dose ACTH in normal subjects

OBJECTIVE The standard ACTH test in clinical use employs a pharmacological dose of ACTH which assesses the maximum secretory capacity of the adrenal cortex. We have investigated the responses of plasma adrenocortical steroids including cortisol, aldosterone and dehydroepiandrosterone (DHEA) to physiological doses of ACTH (ACTH 1–24, tetracosactide, Cortrosyn) and determined the minimal dose which induces a response equivalent to that induced by a pharmacological dose of ACTH.
Secreted Lymphotoxin-α Is Essential for the Control of an Intracellular Bacterial Infection

Although the essential role of tumor necrosis factor (TNF) in the control of intracellular bac-terial infection is well established, it is uncertain whether the related cytokines lymphotoxin-α (LTα3) and lymphotoxin-β (LTβ) have independent roles in this process. Using C57Bl/6 mice in which the genes for these cytokines have been disrupted, we have examined the relative contribution of secreted LTα3 and membrane-bound LTβ in the host response to aerosol Mycobacterium tuberculosis infection. To overcome the lack of peripheral lymph nodes in LTα−/− and LTβ−/− mice, bone marrow chimeric mice were constructed. LTα−/− chimeras, which lack both secreted LTα3 and membrane-bound LTβ (LTα1β2 and LTα2β1), were highly susceptible and succumbed 5 wk after infection. LTβ−/− chimeras, which lack only the membrane-bound LTβ, controlled the infection in a comparable manner to wild-type (WT) chimeric mice. T cell responses to mycobacterial antigens and macrophage responses in LTα−/− chimeras were equivalent to those of WT chimeras, but in LTα−/− chimeras, granuloma formation was abnormal. LTα−/− chimeras recruited normal numbers of T cells into their lungs, but the lymphocytes were restricted to perivascular and peribronchial areas and were not colocated with macrophages in granulomas. Therefore, LTα3 is essential for the control of pulmonary tuberculosis, and its critical role lies not in the activation of T cells and macrophages per se but in the local organization of the granulomatous response.
Machine Learning for Neural Decoding

Abstract Despite rapid advances in machine learning tools, the majority of neural decoding approaches still use traditional methods. Modern machine learning tools, which are versatile and easy to use, have the potential to significantly improve decoding performance. This tutorial describes how to effectively apply these algorithms for typical decoding problems. We provide descriptions, best practices, and code for applying common machine learning methods, including neural networks and gradient boosting. We also provide detailed comparisons of the performance of various methods at the task of decoding spiking activity in motor cortex, somatosensory cortex, and hippocampus. Modern methods, particularly neural networks and ensembles, significantly outperform traditional approaches, such as Wiener and Kalman filters. Improving the performance of neural decoding algorithms allows neuroscientists to better understand the information contained in a neural population and can help to advance engineering applications such as brain–machine interfaces. Our code package is available at github.com/kordinglab/neural_decoding.
Evaluation of the liver protection and toxicity of Da-Huang-Zhe-Chong pill in rats

Context: Da-Huang-Zhe-Chong pill (DHZCP), a classical traditional Chinese formula, consists of 12 crude drugs which have been widely used with significant therapeutic effects. Some drugs in this formula have toxicities that might result in some adverse effects of DHZCP. Objective: The liver protection and toxicity of DHZCP were first evaluated against chronic carbon tetrachloride (CCl4)-induced liver injury in rats. Materials and methods: The rats were treated by intraperitoneal injection of 10% CCl4 for 12 weeks. At the end of week 4, DHZCP at doses of 44 g/kg (high-dose group) and 22 g/kg (low-dose group) was intragastrically administered to CCl4-treated rats, once a day for four weeks. At the end of weeks 8 and 12, the general status of the rats, histopathology of liver, serum alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP) and total bilirubin (TBIL) levels were observed or determined and recorded. By correspondence analysis (CA) on biochemical markers and liver histopathological score (HS), the “dose-time-response” relationship of DHZCP on the hepatic injury rats was evaluated. Results: The results showed that DHZCP exhibited a significant protective effect on liver injury by reversing the biochemical parameters and histopathological changes. However, this hepatoprotective effect may be weakened, or even be transferred to toxicity with the increase of the administration dose (44 g·kg−1·d−1) and time (more than 2 months) of this formula. These results were consistent with the histopathological observation and the serum levels. Discussion and conclusion: Administration of proper dose and time of DHZCP could well play its hepatoprotective effect and even treat hepatitis, but the safety on liver should be considered when large-dose (44 g·kg−1·d−1) DHZCP is used for long time (more than 2 months). We suggest that the administration dose and time of DHZCP in clinical use should not be increased and prolonged, and simultaneously liver function should be regularly monitored.
Re-opening Windows: Manipulating Critical Periods for Brain Development

Editor’s note: The brain acquires certain skills—from visual perception to language—during critical windows, specific times in early life when the brain is actively shaped by environmental input. Scientists like Takao K. Hensch are now discovering pathways in animal models through which these windows might be re-opened in adults, thus re-awakening a brain’s youth-like plasticity. Such research has implications for brain injury repair, sensory recovery, and neurodevelopmental disorder treatment. In addition, what we know today about these critical windows of development already has enormous implications for social and educational policy.
Soluble human epidermal growth factor receptor 2 (HER2) levels in patients with HER2‐positive breast cancer receiving chemotherapy with or without trastuzumab: Results from North Central Cancer Treatment Group adjuvant trial N9831

Increased soluble human epidermal growth factor receptor 2 (sHER2) is an indicator of a poor prognosis in HER2‐positive metastatic breast cancer. In this study, the authors evaluated levels of sHER2 during treatment and at the time of disease recurrence in the adjuvant North Central Cancer Treatment Group N9831 clinical trial.
Foreign Bodies in the Ear, Nose and Throat: An Experience in a Tertiary Care Hospital in Central Nepal

Abstract Introduction A foreign body (FB) is an object or substance foreign to the location where it is found. FBs in the ear, nose, and throat are a common problem frequently encountered in both children and adults. Objective To analyze FBs in terms of type, site, age, and gender distribution and method of removal. Methods A retrospective study was performed in a tertiary care hospital in the central part of Nepal. The study period was from June 2013 to May 2014. The information was obtained from hospital record books. Results A total of 134 patients had FBs in the ear, nose, or throat; 94 were males and 40 were females. Of the 134 patients, 70 (52.23%) had FB in the ear, 28 (20.89%) in the nose, and 36 (26.86%) in the throat. The FB was animate (living) in 28 (40%) patients with FB in the ear and 1 (3.5%) patient with FB in the nose, but the FB was inanimate (nonliving) in any patient with FB in the throat, in 42 (60%) patients with FB in the ear FB, and in 27 (96.4%) patients with FB of the nose. The FB was removed with or without local anaesthesia (LA) in 98 (73.13%) patients, and only 36 patients (26.86%) required general anaesthesia (GA). The most common age group affected was <10 years. Conclusion FBs in the ear and nose were found more frequently in children, and the throat was the most common site of FB in adults and elderly people. Most of the FBs can be easily removed in emergency room or outpatient department.
Efficient Algorithms for Systematic Polar Encoding

Arıkan has laid the foundations of systematic polar codes and has also indicated that the computational complexity order of the systematic polar encoder (SPE) can be the same of a nonsystematic polar encoder (NSPE) i.e., θ(N log N). In this letter, we propose three efficient encoders along with their full pseudocode implementations, all with θ(N log N) complexity. These encoders work for any arbitrary choice of frozen bit indices, and they allow a tradeoff between the number of XOR computations and the number of bits of memory required by the encoder. We show that our best encoder requires exactly the same number of XORs as that of NSPE.
Spatiotemporal Frequency and Direction Sensitivities of Human Visual Areas Measured Using fMRI

Using functional magnetic resonance imaging (fMRI) we have studied the variation in response magnitude, in each visual area (V1-V5), as a function of spatial frequency (SF), temporal frequency (TF) and unidirectional motion versus counterphase flicker. Each visual area was identified in each subject using a combination of retinotopic mapping fMRI and cortical flattening techniques. A drifting (or counterphasing) sinusoidal grating was used as the stimulus in a study in which we parametrically varied SF between 0.4 and 7 cycles/degree and TF between 0 and 18 Hz. For each experiment we constructed fMRI amplitude tuning curves, averaged across subjects, for each visual area. The tuning curves that resulted are consistent with the known physiological properties of cells in the corresponding macaque visual areas, previous functional imaging studies, and in the case of V1, the psychophysically determined contrast sensitivity functions for spatial and temporal frequency. In the case of V3A, the SF tuning functions obtained were more similar to those found in single cell studies of macaque V3 rather than macaque V3A. All areas showed at least a moderate preference for directed versus counterphasing motion with V5 showing the largest preference. Visual areas V1, V2, V3, and V3A showed more direction sensitivity at low spatial frequencies, while VP, V4, and V5 had the highest drifting versus counterphasing ratios for higher spatial frequencies.