Miracle-dz/UniFAR-FTUs huggingface dataset:
Abstract. The lack of reliable animal models to assess the safety and efficacy of drugs and to explore the underlying molecular mechanisms is one of the most severe impedi- ments in head and neck squamous cell carcinoma (HNSCC)

The lack of reliable animal models to assess the safety and efficacy of drugs and to explore the underlying molecular mechanisms is one of the most severe impediments in head and neck squamous cell carcinoma (HNSCC) tumor immunology research. The majority of xenograft tumor models established using immunodeficient mice neglect the effects of T cells. To date, to the best of our knowledge, there is no syngeneic tumor model available that reflects the immune microenvironmental features of HNSCC tumors. To solve this issue, the present study used 4‐nitroquinoline‐1‐oxide (4‐NQO) to induce squamous cell carcinoma in C57BL/6 mice. Three HNSCC cell lines were then established, and one of these, termed JC1, was selected for further analysis due to its enhanced proliferative ability and tumorigenicity in immunodeficient nude mice. However, none of the 3 cell lines could form tumors in immunocompetent mice. Due to the different tumorigenicities in nude and C57BL/6 mice, the immune system may play an important role in inoculated JC1 tumor progression. Chemical induction was used to establish the tumorigenicity‐enhanced cell line, JC1‐2, which can form syngeneic tumors in immunocompetent C57BL/6 mice. Next‐generation sequencing (NGS) was used to perform the immunogenomic and transcriptomic characterization of the JC1‐2 cells. Splenocytes were isolated from C57BL/6 mice and co‐cultured with JC1‐2 cells to verify the responsiveness of the interferon (IFN)‐γ pathway in the JC1‐2 cell line. Unlike the majority of syngeneic mouse tumors, the JC1‐2‐formed tumors resembled ‘inflamed tumors’ due to the abundancy of immune cells in the tumor microenvironment. Moreover, more intense immune responses were observed in the orthotopic mouse model than in the heterotopic model. Thus, this model could be used to delineate the interactions between HNSCC and lymphocytes, and to validate novel immunotherapy targets.
Active Learning for LSTM-autoencoder-based Anomaly Detection in Electrocardiogram Readings

Recently, the amount of generated time series data has been increasing rapidly in many areas such as healthcare, security, meteorology and others. However, it is very rare that those time series are annotated. For this reason, unsupervised machine learning techniques such as anomaly detection are often used with such data. There exist many unsupervised algorithms for anomaly detection ranging from simple statistical techniques such as moving average or ARIMA till complex deep learning algorithms such as LSTM-autoencoder. For a nice overview of the recent algorithms we refer to read [2,1]. Difficulties with the unsupervised approach are: defining an anomaly score to correctly represent how anomalous is the time series, and setting a threshold for that score to distinguish between normal and anomaly data. Supervised anomaly detection, on the other hand, needs an expensive involvement of a human expert. An additional problem with supervised anomaly detection is usually the occurrence of very low ratio of anomalies, yielding highly imbalanced data. In this extended abstract, we propose an active learning extension for an anomaly detector based on a LSTM-autoencoder. It performs active learning using various classification algorithms and addresses data imbalance with oversampling and under-sampling techniques. We are currently testing it on the ECG5000 dataset from the UCR time series classification archive [3].
Response to exercise‐induced blood pressure elevation is blunted in wrist‐cuff automated oscillometric measurement in healthy young college students

A wrist‐cuff automated oscillometric device is portable and useful for self‐monitoring of blood pressure (BP) at home and outdoors when an upper arm device is not available. Although the height of the forearm in wrist BP measurement is acknowledged to be the major cause of measurement error, it remains unclear whether exercise affects subsequent wrist BP measurement.
Association of Phosphatidylinositol-Specific Phospholipase C with Calcium-Induced Biomineralization in the Coccolithophore Emiliania huxleyi

Biomineralization by calcifying microalgae is a precisely controlled intracellular calcification process that produces delicate calcite scales (or coccoliths) in the coccolithophore Emiliania huxleyi (Haptophycea). Despite its importance in biogeochemical cycles and the marine environment globally, the underlying molecular mechanism of intracellular coccolith formation, which requires calcium, bicarbonate, and coccolith-polysaccharides, remains unclear. In E. huxleyi CCMP 371, we demonstrated that reducing the calcium concentration from 10 (ambient seawater) to 0.1 mM strongly restricted coccolith production, which was then recovered by adding 10 mM calcium, irrespective of inorganic phosphate conditions, indicating that coccolith production could be finely controlled by the calcium supply. Using this strain, we investigated the expression of differentially expressed genes (DEGs) to observe the cellular events induced by changes in calcium concentrations. Intriguingly, DEG analysis revealed that the phosphatidylinositol-specific phospholipase C (PI-PLC) gene was upregulated and coccolith production by cells was blocked by the PI-PLC inhibitor U73122 under conditions closely associated with calcium-induced calcification. These findings imply that PI-PLC plays an important role in the biomineralization process of the coccolithophore E. huxleyi.
Regulation of blood–brain barrier integrity by microglia in health and disease: A therapeutic opportunity

The blood–brain barrier (BBB) is a critical regulator of CNS homeostasis. It possesses physical and biochemical characteristics (i.e. tight junction protein complexes, transporters) that are necessary for the BBB to perform this physiological role. Microvascular endothelial cells require support from astrocytes, pericytes, microglia, neurons, and constituents of the extracellular matrix. This intricate relationship implies the existence of a neurovascular unit (NVU). NVU cellular components can be activated in disease and contribute to dynamic remodeling of the BBB. This is especially true of microglia, the resident immune cells of the brain, which polarize into distinct proinflammatory (M1) or anti-inflammatory (M2) phenotypes. Current data indicate that M1 pro-inflammatory microglia contribute to BBB dysfunction and vascular “leak”, while M2 anti-inflammatory microglia play a protective role at the BBB. Understanding biological mechanisms involved in microglia activation provides a unique opportunity to develop novel treatment approaches for neurological diseases. In this review, we highlight characteristics of M1 proinflammatory and M2 anti-inflammatory microglia and describe how these distinct phenotypes modulate BBB physiology. Additionally, we outline the role of other NVU cell types in regulating microglial activation and highlight how microglia can be targeted for treatment of disease with a focus on ischemic stroke and Alzheimer’s disease.
The Effect of Tobacco Smoking and Smoking Cessation on Urinal miRNAs in a Pilot Study

The diseases associated with tobacco smoking affect miRNAs and small single-stranded non-coding RNAs. However, there are no data on urinal miRNAs in healthy smokers. We searched for the possible effect of smoking and smoking cessation on miRNA urine expression. For screening, Affymetrix miRNA 4.0 arrays were used in 33 urine samples obtained from six never smokers and from current smokers in three time-points before smoking cessation (n = 10), after short time abstinence (3–8 weeks), and after long-term abstinence (1 year). For validation, a quantitative (q) polymerase chain reaction (PCR) method was used in 93 urine samples obtained from 18 never smokers and 25 current smokers in three time-points before smoking cessation, after short time abstinence (3–8 weeks), and after long-term abstinence (1 year). In screening analysis, 5 miRNAs (hsa-miR-3620-5p, hsa-miR-3613-5p, hsa-miR-3921, hsa-miR-5094, and hsa-miR-337-3p) were dysregulated in current vs. never smokers after multiple testing corrections. Smoking cessation was accompanied by miRNA dysregulation that did not reach a significant level after a multiple testing correction. In validation analysis, three miRNAs correlated with cotinine, but they were affected neither after smoking cessation nor between current and never smokers. Our whole-genome screening of 2.578 miRNAs and validation suggest that tobacco smoking has no or only a small effect on urinal miRNAs.
Dual-tasking in older women: physical activity or else?

ABSTRACT The interplay between gender, Physical Activity (PA), and Dual Tasking (DT) in older adults is unclear. This study aimed to address DT based on gender and PA level. One-hundred and twenty older adults (81 women and 39 men) participated. Timed up and go test and spatiotemporal gait measures were collected in single and DT conditions. Participants were grouped according to gender and PA level. Physical activity did not explain gender differences, women were slower and had shorter stride lengths when DT regardless of PA level. Findings indicate the necessity for tailored PA and functional interventions to improve women’s performance.
Replisome bypass of transcription complexes and R-loops

Abstract The vast majority of the genome is transcribed by RNA polymerases. G+C-rich regions of the chromosomes and negative superhelicity can promote the invasion of the DNA by RNA to form R-loops, which have been shown to block DNA replication and promote genome instability. However, it is unclear whether the R-loops themselves are sufficient to cause this instability or if additional factors are required. We have investigated replisome collisions with transcription complexes and R-loops using a reconstituted bacterial DNA replication system. RNA polymerase transcription complexes co-directionally oriented with the replication fork were transient blockages, whereas those oriented head-on were severe, stable blockages. On the other hand, replisomes easily bypassed R-loops on either template strand. Replication encounters with R-loops on the leading-strand template (co-directional) resulted in gaps in the nascent leading strand, whereas lagging-strand template R-loops (head-on) had little impact on replication fork progression. We conclude that whereas R-loops alone can act as transient replication blocks, most genome-destabilizing replication fork stalling likely occurs because of proteins bound to the R-loops.
Can Early Postoperative Complications Predict High Morbidity and Decrease Failure to Rescue Following Major Abdominal Surgery?

OBJECTIVE To assess whether specific patterns of early postoperative complications may predict overall severe morbidity after major surgery, warranting early escalation of care and prevention of failure to rescue. SUMMARY OF BACKGROUND DATA It is unclear whether early postoperative complications predict a poor outcome. Detailed knowledge of the chronology and type of early complications after major surgery may alert clinicians when to expect higher risk for subsequent major negative events. METHODS All 90-day postoperative events following complex pancreas, liver, and rectal surgeries, and liver transplantation were analyzed over a 3-year period in a single tertiary center. Each complication was recorded regarding severity, type (cardiac, infectious, etc), etiology (surgical/medical), and timing of occurrence. The Comprehensive Complication Index (CCI), covering the first 7 postoperative days, was calculated as a measure for early cumulative postoperative morbidity. The statistical analysis (descriptive, sequence pattern analyses, and logistic regression analyses) aimed to detect any combinations of events predicting poor outcome as defined by a cumulative CCI ≥37.1 at 90-days. RESULTS The occurrence of ≥2 complications, irrespective of severity, type or etiology, was strongly associated with a severe postoperative course (P < 0.001). Even 2 mild complications (≤ grade II) greatly increased the chance for high morbidity compared to patients with 0 or 1 complication within the first postoperative week (odds ratio 10.2, 95% confidence interval 5.82-17.98). The CCI at postoperative day 7 strongly predicted high 90-day morbidity (odds ratio 3.96 per 10 CCI points, P < 0.001). CONCLUSION Multiple complications of any cause or severity within the first postoperative days represents a "warning-signal" for overall high morbidity by 90 days, which should be used to trigger an escalation of care to prevent failure to rescue and eventually poor outcome.
MAKE-IT—A Lightweight Mutual Authentication and Key Exchange Protocol for Industrial Internet of Things

Continuous development of the Industrial Internet of Things (IIoT) has opened up enormous opportunities for the engineers to enhance the efficiency of the machines. Despite the development, many industry administrators still fear to use Internet for operating their machines due to untrusted nature of the communication channel. The utilization of internet for managing industrial operations can be widespread adopted if the authentication of the entities are performed and trust is ensured. The traditional schemes with their inherent security issues and other complexities, cannot be directly deployed to resource constrained network devices. Therefore, we have proposed a strong mutual authentication and secret key exchange protocol to address the vulnerabilities of the existing schemes. We have used various cryptography operations such as hashing, ciphering, and so forth, for providing secure mutual authentication and secret key exchange between different entities to restrict unauthorized access. Performance and security analysis clearly demonstrates that the proposed work is energy efficient (computation and communication inexpensive) and more robust against the attacks in comparison to the traditional schemes.
MR properties of 19F C3F8 gas in the lungs of healthy volunteers: T2∗ and apparent diffusion coefficient at 1.5T and T2∗ at 3T

To measure the transverse relaxation time ( T2∗ ) and apparent diffusion coefficient (ADC) of 19F‐C3F8 gas in vivo in human lungs at 1.5T and 3T, and to determine the representative distribution of values of these parameters in a cohort of healthy volunteers.
Workplace Violence in Outpatient Physician Clinics: A Systematic Review

Workplace violence (WPV) has been extensively studied in hospitals, yet little is known about WPV in outpatient physician clinics. These settings and work tasks may present different risk factors for WPV compared to hospitals, including the handling/exchange of cash, and being remotely located without security presence. We conducted a systematic literature review to describe what is currently known about WPV in outpatient physician clinics. Six literature databases were searched and reference lists from included articles published from 2000–2019. Thirteen quantitative and five qualitative manuscripts were included which all focused on patient/family-perpetrated violence in outpatient physician clinics. No studies examined other violence types (e.g., worker-on-worker; burglary). The overall prevalence of Type II violence ranged from 9.5% to 74.6%, with the most common form being verbal abuse (42.1–94.3%), followed by threat of assault (14.0–57.4%), bullying (2.5–5.7%), physical assault, (0.5–15.9%) and sexual harassment/assault (0.2–9.3%). Worker consequences included reduced work performance, anger, and depression. Most workers did not receive training on how to manage a violent patient. More work is needed to examine the prevalence and risk factors of WPV in outpatient physician clinics for purposes of informing prevention efforts in these settings.
“eLoriCorps Immersive Body Rating Scale”: Exploring the Assessment of Body Image Disturbances from Allocentric and Egocentric Perspectives

The first objective of this study was to test the convergent and discriminant validity between the “eLoriCorps Immersive Body Rating Scale” and the traditional paper-based figure rating scale (FRS). The second objective was to explore the contribution of the egocentric virtual reality (VR) perspective of eLoriCorps to understanding body image disturbances (BIDs). The sample consisted of 53 female and 13 male adults. Body size dissatisfaction, body size distortion, perceived body size, and ideal body size were assessed. Overall, outcomes showed good agreement between allocentric perspectives as measured via VR and the FRS. The egocentric VR perspective produced different results compared to both the allocentric VR perspective and the FRS. This difference revealed discriminant validity and suggested that eLoricorps’ egocentric VR perspective might assess something different from the traditional conception of body dissatisfaction, which an allocentric VR perspective generally assesses. Finally, the egocentric VR perspective in assessing BIDs deserves to be studied more extensively to explore the possibility of finding two types of body image distortion: (a) an egocentric perceptual body distortion, referring to internal body sensation affected by intra-individual changes, and (b) an allocentric perceptual body distortion, referring to external body benchmarks constructed by inter-individual comparison occurring in a given cultural context.
A Double-Well Ultra-Coarse-Grained Model to Describe Protein Conformational Transitions.

The double-well model is usually used to describe the conformational transition between two states of protein. Since conformational changes usually occur within a relatively large timescale, coarse-grained models are often used to accelerate the dynamic process due to its inexpensive computational cost. In this work, we develop a double-well ultra-coarse-grained (DW-UCG) model to describe the conformational transitions of the adenylate kinase, glutamine-binding protein and lactoferrin. The coarse-grained simulation results show that the DW-UCG model of adenylate kinase captures the crucial intermediate states in the LID-closing and NMP-closing pathways, reflecting the key secondary structural changes in conformational transition. A comparison of the different DW-UCG models of adenylate kinase indicates that an appropriate choice of bead resolution could generate the free energy landscape that is comparable to that from the residue-based model. The coarse-grained simulations for the glutamine-binding protein and lactoferrin also demonstrate that the DW-UCG model is valid in reproducing the correct two-state behaviour for their functional study, which indicate the potential application of the DW-UCG model in investigating the mechanism of conformational changes of large proteins.
VGluT2 Expression in Dopamine Neurons Contributes to Postlesional Striatal Reinnervation

A subset of adult ventral tegmental area dopamine (DA) neurons expresses vesicular glutamate transporter 2 (VGluT2) and releases glutamate as a second neurotransmitter in the striatum, while only few adult substantia nigra DA neurons have this capacity. A subset of adult ventral tegmental area dopamine (DA) neurons expresses vesicular glutamate transporter 2 (VGluT2) and releases glutamate as a second neurotransmitter in the striatum, while only few adult substantia nigra DA neurons have this capacity. Recent work showed that cellular stress created by neurotoxins such as MPTP and 6-hydroxydopamine can upregulate VGluT2 in surviving DA neurons, suggesting the possibility of a role in cell survival, although a high level of overexpression could be toxic to DA neurons. Here we examined the level of VGluT2 upregulation in response to neurotoxins and its impact on postlesional plasticity. We first took advantage of an in vitro neurotoxin model of Parkinson's disease and found that this caused an average 2.5-fold enhancement of Vglut2 mRNA in DA neurons. This could represent a reactivation of a developmental phenotype because using an intersectional genetic lineage-mapping approach, we find that >98% of DA neurons have a VGluT2+ lineage. Expression of VGluT2 was detectable in most DA neurons at embryonic day 11.5 and was localized in developing axons. Finally, compatible with the possibility that enhanced VGluT2 expression in DA neurons promotes axonal outgrowth and reinnervation in the postlesional brain, we observed that DA neurons in female and male mice in which VGluT2 was conditionally removed established fewer striatal connections 7 weeks after a neurotoxin lesion. Thus, we propose here that the developmental expression of VGluT2 in DA neurons can be reactivated at postnatal stages, contributing to postlesional plasticity of dopaminergic axons. SIGNIFICANCE STATEMENT A small subset of dopamine neurons in the adult, healthy brain expresses vesicular glutamate transporter 2 (VGluT2) and thus releases glutamate as a second neurotransmitter in the striatum. This neurochemical phenotype appears to be plastic as exposure to neurotoxins, such as 6-OHDA or MPTP, that model certain aspects of Parkinson's disease pathophysiology, boosts VGluT2 expression in surviving dopamine neurons. Here we show that this enhanced VGluT2 expression in dopamine neurons drives axonal outgrowth and contributes to dopamine neuron axonal plasticity in the postlesional brain. A better understanding of the neurochemical changes that occur during the progression of Parkinson's disease pathology will aid the development of novel therapeutic strategies for this disease.
Ex-Vivo Trans-Corneal and Trans-Scleral Diffusion Studies with Ocular Formulations of Glutathione as an Antioxidant Treatment for Ocular Diseases

Exposure to sunlight and contact with atmospheric oxygen makes the eye particularly susceptible to oxidative stress, which can potentially produce cellular damage. In physiological conditions, there are several antioxidant defense mechanisms within the eye. Glutathione (GSH) is the most important antioxidant in the eye; GSH deficit has been linked to several ocular pathologies. The aim of this study was to explore the potential for newly developed formulations allowing controlled delivery of antioxidants such as GSH and vitamin C (Vit C) directly to the eye. We have investigated the stability of antioxidants in aqueous solution and assessed ex-vivo the diffusion of GSH through two ocular membranes, namely cornea and sclera, either in solution or included in a semisolid insert. We have also carried out the hen’s egg-chlorioallantoic membrane test (HET-CAM) to evaluate the ocular irritancy of the different antioxidant solutions. Our results showed that GSH is stable for up to 30 days at 4 °C in darkness and it is not an irritant to the eye. The diffusion studies revealed that the manufactured formulation, a semisolid insert containing GSH, could deliver this tripeptide directly to the eye in a sustained manner.
Differences in health behaviors related to overweight/obesity by race/ethnicity in a diverse urban commuter college

Abstract Objective: To examine health behaviors associated with overweight/obesity by race/ethnicity at a diverse urban college. Participants: 270 undergraduates (77.0% female; 26.7% non-Hispanic white) and median body mass index (BMI) of 23.1 kg/m2. Methods: A questionnaire about health-related behaviors as part of the “Get Fruved” project was used to measure health behaviors (sugar sweetened beverage (SSB), fruit and vegetable consumption, physical activity, stress, and sleep) by race/ethnicity. Multivariable logistic regression was used to assess the adjusted odds of engaging in positive health-related behaviors. Results: Non-Hispanic black and Hispanic students were 64% and 59% less likely to consume lower amounts of SSB. Hispanic students were 83% and 81% less likely to meet vegetable and fruit recommendations. Non-Hispanic black and other (including biracial) had reduced odds of meeting vegetable recommendations (AOR = 0.18 and 0.28). Conclusions: Disparities in SSB, fruit, and vegetable consumption represent potential intervention targets to improve health behaviors among racial/ethnic minorities.