Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic characterization respiratory syncytial virus in Kerala, the southern part of India

Respiratory syncytial virus (RSV) is an important cause of acute lower respiratory tract infection (ALRI) in infants and young children globally. RSV presents two antigenic groups RSV‐A and ‐B. Genetic variability is also very high within each group. RSV circulation varies year to year and even varies among different regions. Data on circulatory pattern of RSV are available from other parts of India except Kerala. The aim of the study was to generate data about groups and genotypes of circulating RSV in Kerala. In this study, RSV positive samples received during January, 2012 to December, 2014 were used for genetic characterization. The samples were tested by using nucleocapsid (N) gene‐based conventional multiplex reverse transcriptase polymerase chain reaction (RT‐PCR) to identify the RSV group. Genotyping was done by nucleotide sequencing of the C‐terminal region of the glycoprotein (G) gene. Out of the 130 patient samples tested, 49 samples were positive for RSV. Among the positive samples, 32 belong to the RSV‐A and 17 belong to RSV‐B virus. Phylogenetic analysis revealed that all RSV‐A sequences (n = 22) belonged to NA1 genotype and five of the sequences showed the novel 72 nucleotide duplication and clustered into the newly designated ON1 genotype. All RSV‐B sequences (n = 17) were clustered into the BA (BA9 and 10) genotype. From this study, we concluded both RSV‐A and ‐B were co‐circulated in Kerala and RSV‐A was observed predominantly in 2012 and RSV‐B in 2014. As per our best of knowledge, BA10 genotype is first observed in India.
Advances in epilepsy gene discovery and implications for epilepsy diagnosis and treatment

Purpose of review Epilepsy genetics is shifting from the academic pursuit of gene discovery to a clinical discipline based on molecular diagnosis and stratified medicine. We consider the latest developments in epilepsy genetics and review how gene discovery in epilepsy is influencing the clinical classification of epilepsy and informing new therapeutic approaches and drug discovery. Recent findings Recent studies highlighting the importance of mutation in GABA receptors, NMDA receptors, potassium channels, G-protein coupled receptors, mammalian target of rapamycin pathway and chromatin remodeling are discussed. Examples of precision medicine in epilepsy targeting gain-of-function mutations in KCNT1, GRIN2A, GRIN2D and SCN8A are presented. Potential reasons for the paucity of examples of precision medicine for loss-of-function mutations or in non-ion channel epilepsy genes are explored. We highlight how systems genetics and gene network analyses have suggested that pathways disrupted in epilepsy overlap with those of other neurodevelopmental traits including human cognition. We review how network-based computational approaches are now being applied to epilepsy drug discovery. Summary We are living in an unparalleled era of epilepsy gene discovery. Advances in clinical care from this progress are already materializing through improved clinical diagnosis and stratified medicine. The application of targeted drug repurposing based on single gene defects has shown promise for epilepsy arising from gain-of-function mutations in ion-channel subunit genes, but important barriers remain to translating these approaches to non-ion channel epilepsy genes and loss-of-function mutations. Gene network analysis offers opportunities to discover new pathways for epilepsy, to decipher epilepsy's relationship to other neurodevelopmental traits and to frame a new approach to epilepsy drug discovery.
Nitric oxide: new evidence for novel therapeutic indications

Background: Nitric oxide (NO) deficiency is implicated in many pathophysiological processes in mammals. NO is a ubiquitous molecule involved in multiple cellular functions. Uncontrolled or inappropriate production of NO may lead to several disease states including septic shock, rheumatoid and inflammatory arthropathies, and expansion of cerebral damage after stroke. However, to date, there are no therapeutic agents available that can overcome these conditions. Similarly, underproduction of NO by NO synthase or enhanced breakdown of NO also leads to diseases such as hypertension, ischemic conditions, pre-eclampsia, premature delivery, among others. NO donor therapies are indicated in these conditions. Results: Nitroglycerin and nitrates (NO donors) have been used as therapeutic agents for the past century, particularly to treat vascular disease, and the only significant adverse effects are headaches. NO donors are highly cost-effective and have beneficial effects in multiple body systems. When the body cannot generate NO via NO synthase or due to rapid turnover leading to inadequate amounts of NO available for biological homeostasis, administration of exogenous NO, or prolongation of the actions of endogenous NO, are practical ways to supplement NO. Conclusion: Recipients of such therapy include patients with angina pectoris, coronary artery disease, hypertension, osteoporosis, gastrointestinal motility disorders, pregnancy-related disorders including premature delivery, pre-eclampsia, vulvodynia, and erectile dysfunction in men. Postmenopausal NO deficiency is rectified with hormone replacement therapy, which enhances local production of NO. Declining local NO production secondary to estrogen deficiency in postmenopausal women and perhaps in older men could be one of the reasons for age-related increased incidences of cardiovascular events and sexual dysfunction. Thus, in addition to supplementation of NO compounds in acute situations like alleviating angina and erectile dysfunction, chronic NO therapy is cost-effective in decreasing cardiovascular events, and improving the urogenital system and skeletal health.
Treatment options for posttraumatic epilepsy

Purpose of review Posttraumatic seizures (PTS) and posttraumatic epilepsy (PTE) are common and debilitating consequences of traumatic brain injury (TBI). Early PTS result in secondary brain injury by raising intracranial pressure and worsening cerebral edema and metabolic crisis. PTE is a localization-related epilepsy strongly associated with TBI severity, but risk factors for PTE and epileptogenesis are incompletely understood and are active areas of research. Medical management of PTS in adults and children is reviewed. Surgical options for posttraumatic drug-resistant epilepsy are also discussed. Recent findings Continuous electroencephalography is indicated for children and adults with TBI and coma because of the high incidence of nonconvulsive seizures, periodic discharges, and associated secondary brain injury in this population. Neuroinflammation is a central component of secondary brain injury and appears to play a key role in epileptogenesis. Levetiracetam is increasingly used for seizure prophylaxis in adults and children, but variability remains. Summary PTS occur commonly after TBI and are associated with secondary brain injury and worse outcomes in adults and children. Current medical and surgical management options for PTS and PTE are reviewed.
Early steps toward understanding neuronal communication

Purpose of review The computational power of the brain arises from the complex interactions between neurons. One straightforward method to quantify the strength of neuronal interactions is by measuring correlation and coherence. Efforts to measure correlation have been advancing rapidly of late, spurred by the development of advanced recording technologies enabling recording from many neurons and brain areas simultaneously. This review highlights recent results that provide clues into the principles of neural coordination, connections to cognitive and neurological phenomena, and key directions for future research. Recent findings The correlation structure of neural activity in the brain has important consequences for the encoding properties of neural populations. Recent studies have shown that this correlation structure is not fixed, but adapts in a variety of contexts in ways that appear beneficial to task performance. By studying these changes in biological neural networks and computational models, researchers have improved our understanding of the principles guiding neural communication. Summary Correlation and coherence are highly informative metrics for studying coding and communication in the brain. Recent findings have emphasized how the brain modifies correlation structure dynamically in order to improve information-processing in a goal-directed fashion. One key direction for future research concerns how to leverage these dynamic changes for therapeutic purposes.
The Politics of Fear

Fear is the most powerful enemy of reason. Both fear and reason are essential to human survival, but the relationship between them is unbalanced. Reason may sometimes dissipate fear, but fear frequently shuts down reason. As Edmund Burke wrote in England twenty years before the American Revolution, " No passion so effectually robs the mind of all its powers of acting and reasoning as fear. " Our Founders had a healthy respect for the threat fear poses to reason. They knew that, under the right circumstances, fear can trigger the temptation to surrender freedom to a demagogue promising strength and security in return. They worried that when fear displaces reason, the result is often irrational hatred and division. As Justice Louis D. Brandeis later wrote: " Men feared witches and burnt women. " Understanding this unequal relationship between fear and reason was crucial to the design of American self-government. Our Founders rejected direct democracy because of concerns that fear might overwhelm reflective thought. But they counted heavily on the ability of a " well-informed citizenry " to reason together in ways that would minimize the destructive impact of illusory, exaggerated, or excessive fears. " When a man seriously reflects on the precariousness of human affairs, he will become convinced that it is infinitely wiser and safer to form a constitution of our own in a cool deliberate manner, while we have it in our power, " wrote Thomas Paine in his legendary pamphlet Common Sense, specifically warning that the Founders should not take the risk of waiting until some fear seized the public imagination, in which event their reasoning processes would be hampered. Nations succeed or fail and define their essential character by the way they challenge the unknown and cope with fear. And much depends on the quality of their leadership. If leaders exploit public fears to herd people in directions they might not otherwise choose, then fear itself can quickly become a self-perpetuating and freewheeling force that drains national will and weakens national character, diverting attention from real threats deserving of healthy and appropriate fear and sowing confusion about the essential choices that every nation must constantly make about its future.
Digitised evaluation of speech intelligibility using vowels in maxillectomy patients

Among the functional disabilities that patients face following maxillectomy, speech impairment is a major factor influencing quality of life. Proper rehabilitation of speech, which may include prosthodontic and surgical treatments and speech therapy, requires accurate evaluation of speech intelligibility (SI). A simple, less time-consuming yet accurate evaluation is desirable both for maxillectomy patients and the various clinicians providing maxillofacial treatment. This study sought to determine the utility of digital acoustic analysis of vowels for the prediction of SI in maxillectomy patients, based on a comprehensive understanding of speech production in the vocal tract of maxillectomy patients and its perception. Speech samples were collected from 33 male maxillectomy patients (mean age 57.4 years) in two conditions, without and with a maxillofacial prosthesis, and formant data for the vowels /a/,/e/,/i/,/o/, and /u/ were calculated based on linear predictive coding. The frequency range of formant 2 (F2) was determined by differences between the minimum and maximum frequency. An SI test was also conducted to reveal the relationship between SI score and F2 range. Statistical analyses were applied. F2 range and SI score were significantly different between the two conditions without and with a prosthesis (both P < .0001). F2 range was significantly correlated with SI score in both the conditions (Spearman's r = .843, P < .0001; r = .832, P < .0001, respectively). These findings indicate that calculating the F2 range from 5 vowels has clinical utility for the prediction of SI after maxillectomy.
Anxiety and malocclusion are associated with temporomandibular disorders in adolescents diagnosed by RDC/TMD. A cross‐sectional study

BACKGROUND Temporomandibular Disorders (TMD) is a multifactorial condition, which could be associated to occlusal and psychological factors, such as anxiety. OBJECTIVE Investigate if anxiety and malocclusion are associated with the prevalence of TMD in adolescents. METHODS To ensure a population-based representative sample, 934 adolescents aged 10 to 14 years old from Curitiba-PR, Brazil were randomly selected and examined according to Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and malocclusion by a single-calibrated examiner (Kappa > 0.80). Anxiety was assessed according to trait anxiety (STAI-T), categorised as high, moderate and low levels. For occlusal exam, it was considered: Angel's molar relationship, anterior and posterior crossbite, excessive overjet, open and deep bite. The associations were analysed by the crude and adjusted prevalence ration (RPa ) of TMJ, calculated by a Poisson multivariate regression with robust variance (α = 0.05). RESULTS The prevalence of at least one type of malocclusion was found in 52.3%. Anxiety was found in high level (12.2%), moderate (70.4%) and low (17.5%). Presence of high anxiety was significantly associated with the prevalence of TMD symptoms (RPa = 4.06, P < 0.001), as well as the prevalence of myofascial pain (RPa = 24.78; P < 0.001) and prevalence of disc displacement with reduction (RPa = 11.08, P < 0.001). Adolescents Class II had higher prevalence of myofascial pain (Class II RPa = 1.73; P < 0.015) than adolescents Class I. Adolescents Class III presented higher prevalence of myofascial pain (PRa 2.53; P = 0.004) than adolescents Class I. CONCLUSION Anxiety is strongly associated with TMD in adolescents. Presence of Class II or III is associated with higher prevalence of myofascial pain in adolescentsPLESAE check and approve the edit made in the article title.
Recovery of hepatitis C specific T‐cell responses after rituximab therapy in hepatitis C mixed cryoglobulinemic vasculitis

Mixed cryoglobulinemic vasculitis is associated with monoclonal B cell expansion in patients with chronic hepatitis C (HCV) infection. B cell depletion therapy using rituximab, a CD20 monoclonal antibody, has been successful in achieving remission from symptomatic disease. This study investigated whether B cell depletion therapy has an impact on activation of HCV‐specific T cell phenotype and function. Nineteen patients with Hepatitis C mixed cryoglobulinemic vasculitis were treated with 4 cycles of rituximab (375 mg/m2) and variables were measured 6 months after therapy. Using flow cytometry and Enzyme‐Linked Immunospot assay, the number of activated and tissue‐like B cells and number of T cells expressing Programmed cell death protein 1 (PD‐1), T‐cell immunoglobulin and mucin‐domain containing‐3 (TIM‐3), and multiple cytokines were measured before and after rituximab therapy. B cell depletion therapy is associated with a significant (P < 0.0001) decline in peripheral T cells with exhaustive phenotype, from pre‐therapy to post‐therapy‐of rituximab (mean ± standard error): CD4+ (16.9 ± 0.9% to 8.9 ± 1.0%) and CD8+ (6.8 ± 0.6% to 3.0 ± 0.5%) T cells expressing PD‐1 and CD4+ (11.0 ± 1.0% to 6.1 ± 0.8%) and CD8+ (12.7 ± 0.7% to 6.4 ± 0.4%) T cells expressing TIM‐3. In addition, there was a significantly higher percentage of peripheral CD8+ T cells responding to HCV peptide stimulation in vitro secreting IFN‐γ (4.55 ± 0.3 to 9.6 ± 1.0 IFN‐γ/106 PBMCs, P < 0.0001), and more than one cytokine (1.3 ± 0.1% to 3.8 ± 0.2%, P < 0.0001) after therapy compared to pre‐therapy. B cell depletion therapy results in recovery of T cell exhaustion and function in patients with HCV cryoglobulinemic vasculitis.
Clinical assessment of disease severity in recurrent aphthous stomatitis.

BACKGROUND Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal diseases in many parts of the world. However, there is very limited published clinical evidence for the therapies used in this condition. This could be partly due to the difficulty in evaluating the efficacy of oral ulcer treatment objectively. In this paper, we present a method for assessing and monitoring the severity of oral ulcers before and after treatment. METHODS Six ulcer characteristics, number, size, duration, ulcer-free period, site and pain, were used to generate an ulcer severity score (USS). The scores for 223 RAS patients were determined, and 79 were scored again after 3-month therapy with topical betamethasone. RESULTS The scores for the minor RAS group were between 18 and 43 (mean 29.2 ± 5.3). The mean score in the major ulcers group (range: 28-60, mean 39.9 ± 6.1) was significantly greater than in the minor group (P < 0.001). The herpetiform recurrent ulcers score range was wide (range: 18-57, mean 36.6 ± 8.4). The mean severity score decreased significantly after treatment (P < 0.001). CONCLUSIONS The USS was indicative of the disease activity in recurrent oral ulceration. It helped in assessing the efficacy of therapy, as the change in the numerical score reflected the change in ulcer severity in response to treatment. This tool may well prove to be of value in clinical management, research and in clinical trials.
Maturational changes in laminin, fibronectin, collagen IV, and perlecan in germinal matrix, cortex, and white matter and effect of betamethasone

Germinal matrix is selectively vulnerable to hemorrhage in premature infants, and use of prenatal betamethasone is associated with a lower occurrence of germinal matrix hemorrhage. Because the major components of extracellular matrix of the cerebral vasculature—laminin, fibronectin, collagen IV, and perlecan—provide structural stability to blood vessels, we examined whether the expression of these molecules was decreased in the germinal matrix and affected by betamethasone. In both human fetuses and premature infants, fibronectin was significantly lower in the germinal matrix than in the cortical mantle or white matter anlagen. Conversely, laminin α1 gene expression was greater in the human germinal matrix compared with the cortical mantle or white matter. Expression of α1‐ and α2(IV) collagen chains increased with advancing gestational age. Low‐dose prenatal betamethasone treatment enhanced fibronectin level by 1.5–2‐fold whereas a high dose reduced fibronectin expression by 2‐fold in rabbit pups. Because fibronectin provides structural stability to the blood vessels, its reduced expression in the germinal matrix may contribute to the fragility of germinal matrix vasculature and the propensity to hemorrhage in premature neonates. © 2008 Wiley‐Liss, Inc.
Prevalence of high-risk human papillomavirus type 16 and 18 in oral and cervical cancers in population from Gujarat, West India.

BACKGROUND Oral and cervical cancers are major malignancies in men and women, respectively, in India. This study evaluated occurrence of human papillomavirus (HPV) 16 and 18 infections in oral and cervical cancers to estimate HPV-associated burden of these cancers in the population from Gujarat, West India. METHODS A total of 97 malignant oral carcinoma tissues and 52 cervical carcinoma tissues were analyzed by type-specific PCR for the presence of HPV type 16 and 18 infections. RESULTS None of the oral cancer patients revealed the presence of HPV type 16 and 18 infection. In cervical cancer, 31 (59.6%) patients were infected with HPV 16 and 18. Of these 31 HPV-positive cervical cancer patients, 28 (90.3%) were infected with HPV 16 and 3 (9.7%) were infected with HPV 18. CONCLUSION The results suggested that HPV 16 and 18 do not play an important role in oral carcinogenesis in the population from Gujarat, West India. However, HPV 16 is highly prevalent in the cervical cancer patients, which may be considered for planning of prevention programs such as screening and vaccination in women from this region.
Pre‐operative measurement of heart rate variability and incidence of hypotension: authors’ reply

Sir, We appreciate Bein et al.’s interest in our recently published paper (1). In response to their letter, we would like to make a few comments. First, in our study (1), we found that 5-min preoperative measurements of the heart rate variability (HRV) can predict hypotension during general anaesthesia. We agree that there could be circadian fluctuations of HRV, and that the time of day of the measurements might have an impact on the results. In this context, HRV parameters computed from 24-h recordings can be utilized. However, it has been suggested that the interpretation of 24-h long-term recordings is problematic, and short-term recordings of the spectral analysis of HRV under controlled conditions are recommended (2). Moreover, short-term recordings of HRV in a non-laboratory setting have been demonstrated to be reproducible over time and therefore characteristic of an individual (3). In practice, 5-min measurements of HRV prior to the beginning of anaesthesia are more feasible and yield greater generalizability than measurements recorded at certain hours of the day. Second, we demonstrated that total HRV power predicted the incidence of hypotension, and that high-frequency (HF) power predicted the magnitude of systolic blood pressure reduction during anaesthesia maintenance after adjusting for clinical covariates (1). However, Hanss et al. (4, 5) have demonstrated that a higher low-frequency to high-frequency (LF/HF) ratio predicts hypotension during spinal anaesthesia. We discussed in our paper that different mechanisms are responsible for the incidence of hypotension during general anaesthesia and spinal anaesthesia (1). Yet, Bein et al., in their letter, raise the point that LF/HF may be a better predictor of intra-operative hypotension during general anaesthesia. Intra-operative hypotension is frequently observed in diabetics with autonomic dysfunction. It is interesting to learn that a reduction in the absolute power of LF and HF under controlled conditions was observed in individuals with diabetes (1, 6–8), but the LF/HF ratio of diabetics was either comparable to (1, 6) or significantly lower than (8) that of normal subjects. In addition, it seems that LF/HF decreases with increasing duration of diabetes (9) or poor control of blood sugar (8). Thus, the question of whether a shift in LF/HF towards sympathetic predominance (i.e. higher LF/ HF) is associated with intra-operative cardiovascular lability during general anaesthesia remains to be determined. Thus, it is more likely that, in these individuals, the autonomic nervous system fails to compensate completely for the vasodilating effects of anaesthesia. Baroreflex sensitivity reflects vagal modulation of the heart rate by the arterial baroreceptor. Because baroreflex function is an important short-term regulatory system for maintaining blood pressure stability, impaired baroreflex regulation of blood pressure may thus be the most plausible mechanism underlying intra-operative hypotension during general anaesthesia.