Miracle-dz/UniFAR-FTUs huggingface dataset:
Contrast Enhanced Ultrasound: Visualization of Far Field and Classification of Plaque in the Extracranial Carotid Arteries

Ultrasound stratification for the degree of carotid artery disease based solely on lumen reduction has poorly predicted patient outcomes. This pilot study focused on patients with moderate carotid artery stenosis. Our purpose was to use contrast imaging with ultrasound to improve carotid field. A total of 10 patients diagnosed with moderate carotid artery stenosis were rescanned with an administration of a contrast imaging agent. Two-dimensional (2D) imaging, color, and Doppler were utilized to scan the patients. The 20 carotid arteries were blindly read by 2 experienced physicians. Visualization of far field, quality of Doppler envelope, plaque morphology, and overall image quality were semi-quantifiably assessed. With the use of a contrast imaging agent, there was a reduction in interphysician interpretation variability. The Kappa coefficient yielded an increase in agreement for postcontrast imaging in the majority of variables. The Doppler envelope showed improvement from precontrast (0.06) to postcontrast (0.63). The visualization of the far fields demonstrated a significant increase in agreement (0.77, 0.71, and 0.67) postcontrast. Plaque morphology demonstrated enhancement in characterization with contrast (–0.09 to 0.66). In this study, contrast-enhanced ultrasound (CEUS) was found to increase overall image quality. Improved interpretation can enhance risk stratification and with further exploration could be used to guide treatment plans for patients with asymptomatic moderate carotid artery disease.
The evolutionary role of human-specific genomic events

In the short evolutionary time since the human-chimpanzee divergence, approximately 6.6 million years ago, humans have acquired a range of traits that are unique among primates. These include tripling brain size, enhanced cognitive abilities, complex culture, descended larynx structure that enables spoken language, longevity, specific diseases, inferior olfaction, and (in some human populations) adult lactase persistence. These traits were likely to have evolved through various genomic mechanisms, among them gene duplications and gene-culture co-evolution. Several studies have estimated the dates for some of these human lineage genomic events. However, no study to date has performed a genomewide estimate of the dates of all human gene duplications. Moreover, as many of these traits were likely to have evolved via gene-culture coevolutionary mechanisms, investigating the evolution of one of these human-specific traits – lactase persistence – provides a model example for in-depth future investigations of specific human phenotypes. In this study I have investigated an important class of human-specific genomic events – gene duplications (otherwise known as human inparalogues). I have developed a new bioinformatics approach for detecting human lineage-specific inparalogues and the duplication dates for those genes. I show that human-specific inparalogues are non-randomly distributed among biological function classes, and their duplication event dates are non-randomly distributed on a timeline between the date of the human-chimpanzee split and the present. I have also investigated the evolution of the human-specific polymorphic trait – lactase persistence. I have performed a worldwide correlation analysis comparing frequency data on all currently known lactase persistence-associated alleles and the distribution of the lactase persistence phenotype in different human populations. I have also performed a gene-culture co-evolution analysis, employing spatially explicit simulation and Approximate Bayesian Computation to condition simulations on genetic and archaeological data, in order to make inferences on the evolution of lactase persistence and dairying in Europe.
Clinical, laboratory, and genetic studies of families with Charcot-Marie-Tooth type 2C disease

Charcot-Marie-Tooth disease type 2C (CMT2C) is an autosomal dominant neuropathy characterized by limb, diaphragm, and laryngeal muscle weakness. We studied five unrelated families with CMT2C, of which two showed significant linkage to chromosome 12q24.11. Linkage analysis excluded this locus in one of the remaining families, suggesting genetic heterogeneity within this CMT subtype. SNP genotyping of samples from affected individuals in the three linked families did not reveal any deletion or copy number variation. All genes in this region were sequenced and two heterozygous missense mutations were identified in the transient receptor potential, subfamily V, member 4 (TRPV4), at positions c.805C>T and c.806G>A in two families, predicting the amino acid substitutions R269C and R269H, respectively. Two other mutations (R186Q, R232C) and one change of uncertain significance (D584N) were subsequently identified. The R269C and R269H variants were not present in more than 200 controls. TRPV4 is a well known member of the TRP superfamily of cation channels. We confirmed that it is expressed in motor and sensory neurons. The R186, R232, and R269 residues are located in the intracellular N-terminal portion of the TRPV4 protein in the ankyrin repeat domain (ARD); functional domains known to mediate protein-protein interactions. When expressed in HEK293 cells and Xenopus oocytes, R269C and R269H TRPV4 trafficked normally to the cell surface, but caused increased cell toxicity and increased constitutive and activated channel currents compared to wild-type TRPV4. Other mutations in TRPV4 have been previously associated with inherited forms of skeletal dysplasia. When mapped onto the crystal structure of the TRPV4 ARD, the mutations found in bone diseases lie on the opposite face of the domain compared to those causing neuropathy. Our findings indicate that TRPV4 mutations cause a degenerative disorder of peripheral nerves. Thus, there is striking phenotypic variability with different mutations in this important channel protein.
The Essential Role of Home- and Community-Based Physical Therapists During the COVID-19 Pandemic

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronoavirus disease 2019 (COVID-19), is a particularly contagious and virulent pathogen. Widespread mitigation strategies to reduce the spread of COVID-19 are now underway in the United States, with strict social distancing recommendations in place nationally, and with most states implementing even stricter stay-at-home orders that limit work-related travel outside the home to only those performing “essential” jobs. Physical therapists are considered essential workers under state and federal guidelines; guidelines and rationale for delivery and utilization of acute care physical therapy have already been published. The American Physical Therapy Association and state boards of physical therapy also support provision of home and community-based physical therapy care to patients who could be harmed by delayed or cancelled therapy sessions.
Potential Protective Role of SDF-1 and CXCR4 Gene Variants in the Development of Dementia.

BACKGROUND The aim of this study was to evaluate the role of polymorphisms of stromal cell-derived factor-1 (SDF-1) and chemokine receptor-4 (CXCR4) genes in dementia susceptibility in a Turkish population. SUBJECTS AND METHODS The study group included 61 dementia patients, while the control group comprised 82 healthy individuals. Gene polymorphisms of SDF-1 3'A G801A (rs1801157) and CXCR4 C138T (rs2228014) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS A significantly reduced risk for developing dementia was found for the group bearing an A allele for SDF-1 3'A polymorphism (p=0.009; χ2=6.812; OR=0.626; 95%CI= 0.429-0.913). The frequency of the CXCR4 TT and TC genotype was significantly lower in patients with dementia compared to controls (p=0.028; χ2=5.583; OR=0.215; 95%CI=0.05-0.914); (p=0.027; χ2=4.919; OR=0.484; 95% CI=0.246-0.955). Additionally, combined genotype analysis showed that the frequency of SDF1 GA-CXCR4 CC was significantly lower in patients with dementia in comparison with those of controls (p=0.049; OR=0.560; 95% CI= 0.307±1.020). CONCLUSIONS Our study provides new evidence that SDF1 A and CXCR4 T alleles may be associated with a decreased dementia risk. The present study is important because to our knowledge, it is the first one to be conducted in a Turkish population to date, but we believe that more patients and controls are needed to obtain statistically significant results.
Mandarin lexical tone recognition in bimodal cochlear implant users

Abstract Objective: To assess the recognition of lexical tones in Mandarin-speaking bimodal cochlear implant (CI) subjects. Design: Lexical tone recognition in quiet and noise (SNR= +5 dB) was measured with electric stimulation (CI alone) or bimodal stimulation (CI + hearing aid (HA)). The recognition and confusion rates of the four tones (T1, T2, T3 and T4) were analysed. Spearman correlation analysis was performed to examine the relationship between hearing levels in the contralateral ear and bimodal benefits. Study sample: Twenty native Mandarin-speaking bimodal CI users, with ages ranging from 16–49 years. Results: Relative to the CI alone, mean tone recognition with the CI + HA improved significantly from 84.1–92.1% correct in quiet (+8 points) and from 57.9–73.1% correct in noise (+15.2 points). Tone confusions between T2 and T3 were the most prominent in all test conditions, and T4 tended to be labelled as T3 in noise. There was no significant correlation between the bimodal benefits for tone recognition and the unaided or HA-aided pure-tone thresholds at 0.25 kHz. Conclusion: Listeners with CI + HA exhibited significantly better tone recognition than with CI alone. The bimodal advantage for tone recognition was greater in noise than in quiet, perhaps due to a ceiling effect in quiet.
Co-Morbidity between Major Depression and Schizophrenia: Prevalence and Clinical Characteristics.

BACKGROUND The aim of this study was to explore the co-morbidity between Major Depressive Disorder (MDD) and Schizophrenia (SZ) among a large number of patients describing their clinical characteristics and rate of prevalence. SUBJECTS AND METHODS A cohort-study was carried out on 396 patients affected by MDD and SZ who consecutively attended the Department of Psychiatry, Rumeilah Hospital in Qatar. We employed the World Health Organization - Composite International Diagnostic Interview (WHO-CIDI) and the Structured Clinical Interview for DSM-5 (SCID-5) for diagnoses. Patients were also grouped in MDD patients with and without co-morbid SZ (MDD vs MDD/SZ) for comparisons. RESULTS A total of 396 subjects were interviewed. MDD patients with comorbid SZ (146(36.8%)) were 42.69±14.33 years old whereas MDD without SZ patients (250 (63.2%)) aged 41.59±13.59. Statistically significant differences between MDD with SZ patients and MDD without SZ patients were: higher BMI (Body Mass Index) (p=0.025), lower family income (p=0.004), higher rate of cigarette smoking (p<0.001), and higher level of consanguinity (p=0.023). Also, statistically significant differences were found in General Health Score (p=0.017), Clinical Global Impression-BD Score (p=0.042), duration of illnesses (p=0.003), and Global Assessment of Functioning (p=0.012). Rates of anxiety dimensions (e.g.: general anxiety, agoraphobia, somatisation, etc.), mood dimensions (e.g.: major depression, mania, oppositional defiant behaviour, Bipolar disorder), Attention Deficit Hyperactivity Disorder, psychotic and personality dimensions were higher among MDD with SZ patients than MDD without SZ. CONCLUSION This study confirms that MDD with SZ is a common comorbidity especially among patients reporting higher level of consanguinity. MDD/SZ comorbidity presents unfavourable clinical characteristics and higher levels of morbidity at rating scales.
Predicting Protein Functions Based on Differential Co-expression and Neighborhood Analysis

Proteins are polypeptides essential in biological processes. Protein physical interactions are complemented by other types of functional relationship data including genetic interactions, knowledge about co-expression, and evolutionary pathways. Existing algorithms integrate protein interaction and gene expression data to retrieve context-specific subnetworks composed of genes/proteins with known and unknown functions. However, most protein function prediction algorithms fail to exploit diverse intrinsic information in feature and label spaces. We develop a novel integrative method based on differential Co-expression analysis and Neighbor-voting algorithm for Protein Function Prediction, namely CNPFP. The method integrates heterogeneous data and exploits intrinsic and latent linkages via global iterative approach and genomic features. CNPFP performs three tasks: clustering, differential co-expression analysis, and predicts protein functions. Our aim is to identify yeast cell cycle-specific proteins linked to differentially expressed proteins in the protein-protein interaction network. To capture intrinsic information, CNPFP selects the most relevant feature subset based on global iterative neighbor-voting algorithm. We identify eight condition-specific modules. The most relevant subnetwork has 87 genes highly enriched with cyclin-dependent kinases, a protein kinase relevant for cell cycle regulation. We present comprehensive annotations for 3538 Saccharomyces cerevisiae proteins. Our method achieves an AUROC of 0.9862, accuracy of 0.9710, and F-score of 0.9691. From the results, we can summarize that exploiting intrinsic nature of protein relationships improves the quality of function prediction. Thus, the proposed method is useful in functional genomics studies.
Multi-component microscale biosynthesis of unnatural cyanobacterial indole alkaloids.

Genome sequencing and bioinformatics tools have facilitated the identification and expression of an increasing number of cryptic biosynthetic gene clusters (BGCs). However, functional analysis of all components of a metabolic pathway to precisely determine biocatalytic properties remains time-consuming and labor intensive. One way to speed this process involves micro-scale cell free protein synthesis (CFPS) for direct gene to biochemical function analysis, which has rarely been applied to study multi-component enzymatic systems in secondary metabolism. We sought to establish an in vitro transcription/translation (TT)-assay to assess assembly of cyanobacterial-derived hapalindole-type natural products (cNPs) due to their diverse bioactivity profiles and complex structural diversity. Using a CFPS system including a plasmid bearing famD2 prenyltransferase from Fischerella ambigua UTEX 1903, we showed production of the central prenylated intermediate (3GC) in the presence of exogenous geranyl-pyrophosphate (GPP) and cis-indole isonitrile. Further addition of a plasmid bearing the famC1 Stig cyclase resulted in synthesis of both FamD2 and FamC1 enzymes, which was confirmed by proteomics analysis, and catalyzed assembly of 12-epi-hapalindole U. Further combinations of Stig cyclases (FamC1-C4) produced hapalindole U and hapalindole H, while FisC identified from Fischerella sp. SAG46.79 generated 12-epi-fischerindole U. The CFPS system was further employed to screen six unnatural halogenated cis-indole isonitrile substrates using FamC1 and FisC, and the reactions were scaled-up using chemoenzymatic synthesis and identified as 5- and 6-fluoro-12-epi-hapalindole U, and 5- and 6-fluoro-12-epi-fischerindole U, respectively. This approach represents an effective, high throughput strategy to determine the functional role of biosynthetic enzymes from diverse natural product BGCs. Key words: biosynthetic gene cluster (BGC), cell free protein synthesis (CFPS), hapalindole, fischerindole, in vitro TT-assay.
Central injection of neuropeptide Y modulates sexual behavior in male rats: interaction with GnRH and kisspeptin/neurokinin B/dynorphin

Abstract Aims A number of studies have shown that neuropeptide Y (NPY) is considered to be one of the key regulators of hypothalamic-pituitary-gonadal (HPG) axis in the mammals. In addition, kisspeptin (encode by Kiss1 gene), neurokinin B (encode by Tac3 gene) and dynorphin (encode by Pdyn gene) (commonly known as KNDy secreting neurons) are a powerful upstream regulators of GnRH neuron in hypothalamus. Materials and Methods The present study aims to investigate the effects of the intracerebroventricular (icv) injection of NPY and BIBP3226 (NPY receptor antagonist (NPYRA)) on the male sexual behavioral. Additionally, in order to see whether NPY signals can be relayed through the pathway of kisspeptin/neurokinin B/dynorphin, the gene expression of these peptides along with Gnrh1 gene in the hypothalamus were measured. Results The icv injection of NPY decreased the latencies and increase the frequencies of sexual parameters of the male rats in a significant way. In this line, NPYRA antagonized the stimulative effects of NPY. Moreover, data from real-time quantitative PCR indicated that injection of NPY significantly increased the gene expression of Gnrh1, Kiss1 and Tac3 and decrease the Pdyn while treatment with NPYRA controlled the modulative effects of NPY on these gene expression. Conclusions In conclusion based on the results of this study, NPY can exert its impacts on the sexual behavior of male rats via modulation of the KNDy secreting neurons as an interneural pathway to GnRH neurons.
Going Once, Going Twice: Using Willingness-to-Accept Auctions to Promote Smoking Cessation.

INTRODUCTION Incentive-based smoking cessation interventions increase quit rates. The optimal incentive, however, is unknown. We used a willingness-to-accept (WTA) auction where smokers submitted bids indicating the incentive they would need to receive for one week of smoking cessation. METHODS Smokers ready to quit (n=35) participated in a WTA auction, naming the amount they needed to be paid to quit for one week. Auction winners received an incentive if they successfully quit. All smokers received nicotine replacement therapy and self-help cessation materials. Carbon monoxide concentrations were monitored remotely 3 times during the week and in person at the final session. RESULTS Participants who smoked their first cigarette within 5 minutes of waking demanded a significantly larger incentive in exchange for quitting than those who waited (p<.05). 45% of auction winners quit smoking compared to 20% of nonwinners (p<.05). The cost per quit was $466 among auction winners compared to $894 among nonwinners. CONCLUSIONS WTA auctions may be an effective way to determine the amount smokers need to be paid to quit, which would allow researchers to estimate the most cost-effective payment to offer as part of incentive-based smoking cessation programs. Replication evaluating longer-term cessation outcomes with larger samples is warranted.
Acute Cognitive Effects of the Hypocretin Receptor Antagonist Almorexant Relative to Zolpidem and Placebo: A Randomized Clinical Trial.

STUDY OBJECTIVES Hypnotic medications can adversely affect behavior during unanticipated awakenings during the night. Animals treated with the hypocretin receptor antagonist almorexant (ALM) have less acute cognitive impairment compared to the GABAA receptor modulator zolpidem (ZOL). This study aimed to determine whether ALM produces less acute cognitive impairment than ZOL in human subjects. METHODS Healthy, young adult, unmedicated male and female subjects participated in a controlled trial of a single dose of ALM 100mg (N = 48), ALM 200mg (N = 53), ZOL 10mg (N = 49), and placebo (PBO, N = 52). RESULTS ZOL and both doses of ALM produced similar levels of subjective sleepiness and impaired the ability of subjects to remain awake in a dark, low stimulus setting relative to PBO. For most cognitive measures, performance under ZOL was significantly worse than ALM or PBO. For tasks involving verbal memory or visual-motor coordination, ZOL impaired performance, whereas the 2 doses of ALM were no different than PBO. For tasks involving higher order executive function, ZOL produced impairment in processing speed and inhibitory control, whereas the 2 doses of ALM were no different than PBO. Performance decrements for ALM were less than ZOL but greater than PBO for some reaction time measures. CONCLUSION The data provide support for the hypothesis that hypocretin receptor (Hcrt) antagonists produce less functional impairment than a benzodiazepine receptor agonist (BzRA). These observations are particularly relevant to patients treated with sedative-hypnotics who are at elevated risk for falls and other untoward events during the intended hours for sleep.
Chloroacétaldéhyde : de l’implication dans les mécanismes physiopathologiques de la néphrotoxicité de l’ifosfamide à la contribution à son effet anticancéreux

Le chloroacetaldehyde (CAA), un des principaux produits du metabolisme hepatique de l’ifosfamide (IFO), est considere comme responsable de la nephrotoxicite de ce medicament. Les mecanismes exacts de cette nephrotoxicite ne sont pas completement elucides. Dans la premiere partie de cette etude, nous avons essaye de preciser les mecanismes physiopathologiques de la toxicite du CAA sur un modele de tranches de cortex renal de rat, puis, dans la deuxieme partie, nous avons recherche un effet anticancereux eventuel du CAA sur des cellules de cancer du sein humain (MCF-7). La nephrotoxicite du CAA, utilise a des concentrations proches de celles mesurees chez les patients traites par l’IFO, soit 0 - 75 µM, s’est manifestee par une chute d’ATP et du glutathion ainsi que par une inhibition du metabolisme du lactate. Certaines enzymes de la neoglucogenese, notamment la glyceraldehyde 3-phosphate deshydrogenase, ont ete inhibees par le CAA. Le complexe I de la chaine respiratoire mitochondriale ainsi que l’oxydation du lactate ont ete egalement inhibees par le toxique. D’autre part, le CAA (10 et 25 µM) a inhibe la proliferation des cellules MCF-7 sans que cette inhibition soit accompagnee d’une chute d’ATP cellulaire. Le transport cellulaire et le metabolisme du glucose ainsi que certaines enzymes de la glycolyse ont ete egalement inhibes par le CAA. Parmi celles-ci, l’hexokinase semble etre l’enzyme qui catalyse l’etape limitante de la voie de la glycolyse. En conclusion, le CAA est bien implique dans les mecanismes de la nephrotoxicite de l’IFO, mais de plus, il pourrait, via l’inhibition de la glycolyse, contribuer a l’effet therapeutique de l’IFO.