Miracle-dz/UniFAR-FTUs huggingface dataset:
Men and Oral Health: A Review of Sex and Gender Differences

Sex and gender related health disparities in oral health remain an underappreciated and often over looked aspect of well-being. The goal of this narrative review is to identify sex and gender related oral health disparities by summarizing the current literature related to differences in oral health between men and women. The review identified that men are more likely to: ignore their oral health, have poorer oral hygiene habits, and experience higher rates of periodontal disease, oral cancer, and dental trauma. Men also visit dentists less frequently and compared to women seek oral treatment more often for an acute problem and less often for disease prevention. Women exhibit more positive attitudes about dental visits, greater oral health literacy, and demonstrate better oral health behaviors than men. Men disproportionately develop periodontal diseases due to a combination of biological and gender related reasons including immune system factors, hormone differences, poorer oral hygiene behaviors, and greater tobacco use. There is a male to female ratio of 2:1 for oral cancer, largely attributable to more tobacco use, heavier use of alcohol, and longer sun exposure. Minority men experience a disproportionate burden of oral health disparities because of both their gender and race/ethnic identities. In conclusion, this review identifies several differences between men and women related to oral health and highlights the need for further research to better understand these disparities and how to incorporate them into developing prevention, education and treatment strategies to improve oral health in men.
Neuroimmune metabolism: Uncovering the role of metabolic reprogramming in central nervous system disease

The rapidly expanding field of immunometabolism has highlighted an intricate association between the metabolic pathways that program cellular pro‐inflammatory versus anti‐inflammatory activity. This Special Issue on Neuroimmune Metabolism showcases a growing body of work characterizing the metabolic profiles of the major CNS‐resident and peripheral immune cell players in neuroinflammation, neurodegeneration, and brain injury. The review articles address the roles of glycolytic, oxidative, and lipid metabolism that are associated with beneficial or detrimental properties in various neurological conditions, address unanswered questions in the field, and discuss promising avenues for future therapeutics.
God Representation Types Are Associated With Levels of Personality Organization and Christian Religious Orthodox Culture

Supplemental digital content is available in the text. Abstract This exploratory study shows that God representation types are associated with levels of personality organization. Among two Dutch samples of psychiatric patients (n = 136) and nonpatients (n = 161), we found associations between the psychotic, borderline, and neurotic personality organizations, and passive-unemotional, negative-authoritarian, and positive-authoritative God representation types, respectively. Both patients and nonpatients reported positive God representations, but only nonpatients and higher-level functioning patients reported an integrated God-object relation. For persons with personality pathology, the relationship with God can be a struggle and might have a defensive and/or compensating function. In addition to personality organization, Christian religious orthodox culture is a statistical predictor of God representations, but not of anger toward God. We offer suggestions for how psychotherapeutic work with God representations might differ for patients with different levels of personality organization.
Association between pre-treatment perfusion profile and cerebral edema after reperfusion therapies in ischemic stroke

The relationship between reperfusion and edema is unclear, with experimental and clinical data yielding conflicting results. We investigated whether the extent of salvageable and irreversibly-injured tissue at baseline influenced the effect of therapeutic reperfusion on cerebral edema. In a pooled analysis of 415 patients with anterior circulation large vessel occlusion from the Tenecteplase-versus-Alteplase-before-Endovascular-Therapy-for-Ischemic-Stroke (EXTEND-IA TNK) part 1 and 2 trials, associations between core and mismatch volume on pre-treatment CT-Perfusion with cerebral edema at 24-hours, and their interactions with reperfusion were tested. Core volume was associated with increased edema (p < 0.001) with no significant interaction with reperfusion (p = 0.82). In comparison, a significant interaction between reperfusion and mismatch volume (p = 0.03) was observed: Mismatch volume was associated with increased edema in the absence of reperfusion (p = 0.009) but not with reperfusion (p = 0.27). When mismatch volume was dichotomized at the median (102 ml), reperfusion was associated with reduced edema in patients with large mismatch volume (p < 0.001) but not with smaller mismatch volume (p = 0.35). The effect of reperfusion on edema may be variable and dependent on the physiological state of the cerebral tissue. In patients with small to moderate ischemic core volume, the benefit of reperfusion in reducing edema is related to penumbral salvage.
Canadian Rheumatologists’ Perspectives on Moderate Psoriatic Arthritis and Oligoarticular Psoriatic Arthritis

Objective Psoriatic arthritis (PsA) substantially impairs quality of life. Clinical trials generally focus on polyarticular PsA, but less is known about the assessment and management of oligoarticular and moderate PsA. An online survey was conducted to determine Canadian rheumatologists’ perspectives on the definition and treatment of oligoarticular and moderate PsA. Methods Regional and national experts treating patients with PsA were asked to complete an online survey to assess their approach to identifying and managing patients with PsA. Survey questions were developed based on guidance from a committee of Canadian rheumatologists. Results Sixty-four of 78 rheumatologists responded, representing 6 major Canadian provinces. Nearly half of respondents were in practice > 20 years. The majority of rheumatologists reported using swollen joint count (SJC) to describe moderate PsA (86.4%) and oligoarticular PsA (96.7%), and considered location of inflammation in PsA assessments. SJC cutoff scores for reporting moderate PsA varied among rheumatologists, suggesting lack of an agreed-upon definition for moderate PsA. Sixty-eight percent of rheumatologists identified access to treatment as the greatest challenge with oligoarticular PsA. Conclusion According to the surveyed rheumatologists, SJC remains a key assessment variable when defining oligoarticular and moderate PsA. Although the number of joints is considered when determining the effect of PsA on patients, joint location and functional impairment are also considered when describing the disease as moderate. Access to treatment for patients with < 5 affected joints is challenging.
Current directions in combining simulation-based macromolecular modeling approaches with deep learning

ABSTRACT Introduction: Structure-guided drug discovery relies on accurate computational methods for modeling macromolecules. Simulations provide means of predicting macromolecular folds, of discovering function from structure, and of designing macromolecules to serve as drugs. Success rates are limited for any of these tasks, however. Recently, deep neural network-based methods have greatly enhanced the accuracy of predictions of protein structure from sequence, generating excitement about the potential impact of deep learning. Areas covered: This review introduces biologists to deep neural network architecture, surveys recent successes of deep learning in structure prediction, and discusses emerging deep learning-based approaches for structure-function analysis and design. Particular focus is given to the interplay between simulation-based and neural network-based approaches. Expert opinion: As deep learning grows integral to macromolecular modeling, simulation- and neural network-based approaches must grow more tightly interconnected. Modular software architecture must emerge allowing both types of tools to be combined with maximal versatility. Open sharing of code under permissive licenses will be essential. Although experiments will remain the gold standard for reliable information to guide drug discovery, we may soon see successful drug development projects based on high-accuracy predictions from algorithms that combine simulation with deep learning – the ultimate validation of this combination’s power.
Role of γ-Secretase Inhibitors for the Treatment of Diverse Disease Conditions through Inhibition of Notch Signaling Pathway.

γ-Secretase is an intramembrane protease sub-assembly which that sunders transmembrane proteins. They are involved in intramembrane proteolysis and also contribute to the regeneration of transmembrane protein. The amyloid precursor protein (APP) is a typical γ-secretase substrate. These proteins are cleaved to produce 36-43 amyloid-beta (Aβ) amino acid peptides. Abnormal folding of these protein fragments leads to amyloid plaques; , frequently encountered in Alzheimer's disease. Some Type I class of integral membrane proteins are processed under the influence of γ-secretase, such as receptor tyrosine-protein kinase erbB4 and CD44 glycoprotein. γ-Secretase is being explored in a number of diseases as a clinical goal. Both γ-secretase inhibitors (GSIs) and γ-secretase modulators (GSMs) are being evaluated for this purpose. A large amount of γ-secretase inhibitors (GSIs) from peptide to non-peptide have been disclosed, offering several lead compounds for the design and optimization of γ-secretase targets, but most GSIs lacks sufficient potency, low penetration in the brain, and low selectiveness. γ-Secretase inhibitors are obliquely a regulator of a γ-secretase substrate Notch, and valuable in the understanding of the development of β-amyloid peptide (Aβ). These γ-secretase inhibitors block the Notch signaling pathway in autoimmune and lymphoproliferative disorders like autoimmune lymphoproliferative syndrome (ALPS) and systemic lupus erythematosus (SLE), and perhaps even in cancerous cell proliferation, angiogenesis, and cellular differentiation of human-induced pluripotent stem cells (hiPSC). The current review portrays the mechanism, regulation, and inhibition of γ-secretase in the management of a wide assortment of diseases.
Meta-Analytic Findings on Reading in Children With Cochlear Implants.

This meta-analysis study aims to quantify the group differences in reading skills between children with cochlear implants and their hearing peers and between children with cochlear implants and children with hearing aids (aged between 3 and 18 years old). Of the 5,642 articles screened, 47 articles met predetermined inclusion criteria (published between 2002 and 2019). The robust variance estimation based meta-analysis models were used to synthesize all the effect sizes. Children with cochlear implants scored significantly lower than their hearing peers in phonological awareness (g = -1.62, p < 0.001), vocabulary (g = -1.50, p < 0.001), decoding (g = -1.24, p < 0.001), and reading comprehension (g = -1.39, p < 0.001), but not for fluency (g = -0.67, p = 0.054). Compared to children with hearing aids, children with cochlear implants scored significantly lower in phonological awareness (g = -0.30, p = 0.028). The percentage of unilateral cochlear implant negatively impacts the group difference between children with cochlear implants and their hearing peers. Findings from this study confirm a positive shift in reading outcomes for profoundly deaf children due to cochlear implantation. Some children with cochlear implants may need additional supports in educational settings.
Mechanism of Curcuma longa and Its Neuroactive Components for the Management of Epileptic Seizures: A Systematic Review

Curcuma longa (Turmeric) is a tropical herbaceous perennial plant of the family Zingiberaceae and contains curcuminoids, sesquiterpenoids and monoterpenoids as its major components. Given the broad range of activities that Curcuma longa possesses and also its use as a traditional epilepsy remedy, this review attempts to systematically review the experimentally proven activities of Curcuma longa and its bioactive components, which are related to the management of epileptic seizures. Using the PRISMA model, five databases (Google Scholar, PubMed, ScienceDirect, SCOPUS and SpringerLink) were searched using the keywords [“Curcuma longa” AND “Epilepsy”] and [“Curcuma longa” AND “Seizures”], leaving 34 articles that met the inclusion criteria. The present systematic review elaborated on the experimentally proven potential of Curcuma longa components, such as an aqueous extract of Curcuma longa itself, Curcuma longa oil and active constituents like curcuminoids and bisabolene sesquiterpenoids found in Curcuma longa with anti-seizure potential. Using human equivalent dose calculations, human treatment parameters were suggested for each component by analysing the various studies in this review. This review also determined that the principal components possibly exert their anti-seizure effect via the reduction of corticosterone, modulation of neurotransmitters signalling, modulation of sodium ion channels, reduction of oxidative DNA damage, reduction of lipid peroxidation, upgregulation of brain-derived neurotrophic factor (BDNF) and γ-aminobutyric acid (GABA) mediated inhibition. It is anticipated that this review will help pave the way for future research into the development of Curcuma longa and its neuroactive constituents as potential drug candidates for the management of epilepsy.
Mutations in HID1 Cause Syndromic Infantile Encephalopathy and Hypopituitarism

Precursors of peptide hormones undergo posttranslational modifications within the trans‐Golgi network (TGN). Dysfunction of proteins involved at different steps of this process cause several complex syndromes affecting the central nervous system (CNS). We aimed to clarify the genetic cause in a group of patients characterized by hypopituitarism in combination with brain atrophy, thin corpus callosum, severe developmental delay, visual impairment, and epilepsy.
Supporting Real World Decision Making in Coronary Diseases Using Machine Learning

Cardiovascular diseases are one of the leading global causes of death. Following the positive experiences with machine learning in medicine we performed a study in which we assessed how machine learning can support decision making regarding coronary artery diseases. While a plethora of studies reported high accuracy rates of machine learning algorithms (MLA) in medical applications, the majority of the studies used the cleansed medical data bases without the presence of the “real world noise. ” Contrary, the aim of our study was to perform machine learning on the routinely collected Anonymous Cardiovascular Database (ACD), extracted directly from a hospital information system of the University Medical Centre Maribor). Many studies used tens of different machine learning approaches with substantially varying results regarding accuracy (ACU), hence they were not usable as a base to validate the results of our study. Thus, we decided, that our study will be performed in the 2 phases. During the first phase we trained the different MLAs on a comparable University of California Irvine UCI Heart Disease Dataset. The aim of this phase was first to define the “standard” ACU values and second to reduce the set of all MLAs to the most appropriate candidates to be used on the ACD, during the second phase. Seven MLAs were selected and the standard ACUs for the 2-class diagnosis were 0.85. Surprisingly, the same MLAs achieved the ACUs around 0.96 on the ACD. A general comparison of both databases revealed that different machine learning algorithms performance differ significantly. The accuracy on the ACD reached the highest levels using decision trees and neural networks while Liner regression and AdaBoost performed best in UCI database. This might indicate that decision trees based algorithms and neural networks are better in coping with real world not “noise free” clinical data and could successfully support decision making concerned with coronary diseasesmachine learning.
Pre-operative Weight Loss Program for Obese Patients Undergoing Laparoscopic Gastrectomy.

Background : The aim of this study was to investigate the influence of obesity and the usefulness of a pre-operative weight loss program (PWLP) for obese patients undergoing laparoscopic gastrectomy (LG) for gastric cancer (GC). Materials and Methods : Study1 : 219 patients who underwent laparoscopic distal gastrectomy (LDG) for GC were divided into 2 groups : body mass index (BMI) ≧ 28 and BMI < 28kg / m2. The influence of BMI in LG surgery was investigated. Study2 : The BMI ≧ 28 kg / m2 patients with a planned LG (n = 8) undertook a PWLP including calorie restriction and exercise. The effects of this program were evaluated. Results : Study1 : The BMI ≧ 28kg / m2 group showed significantly longer operation times, more blood loss and a higher frequency of post-operative complications than that of the BMI < 28kg / m2 group. Study 2 : The patients achieved a weight loss of 4.2%. The visceral fat area (VFA) was significantly decreased by 10.6%, whereas skeletal muscle mass was unaffected. The PWLP group showed shorter operation times, less blood loss and a lower frequency of post-operative complications compared with that of the BMI ≧ 28kg / m2 group. Conclusion : Obesity is an important risk factor and a pre-operative weight loss program is useful for obese patients undergoing a LG. J. Med. Invest. 68 : 165-169, February, 2021.
A cascade of care for alcohol use disorder: Using 2015-2019 National Survey on Drug Use and Health data to identify gaps in past 12-month care.

BACKGROUND Although effective treatments exist, alcohol use disorder (AUD) is undertreated. We used a cascade of care framework to understand gaps in care for persons with AUD. METHODS Using 2015-2019 National Survey on Drug Use and Health data, we evaluated the following steps in the cascade of care: (1) adult prevalence of AUD; (2) proportion of adults with AUD who utilized health care in the past 12 months; (3) proportion with AUD screened about their alcohol use; (4) proportion with AUD who received a brief intervention about their alcohol misuse; (5) proportion with AUD who received information about treatment for alcohol misuse; and (6) proportion with AUD who received treatment. Analyses were stratified by AUD severity. RESULTS Of the 214,505 persons included in the sample, the weighted prevalence of AUD was 7.8% (95% CI 7.6-8.0%). Cascades of care showed the majority of individuals with AUD utilized health care in the past 12 months [81.4% (95% CI 80.7-82.1%)] and were screened about alcohol use [69.9% (95% CI 68.9-70.8%)]. However, only a minority of individuals received subsequent steps of care, including 11.6% (95% CI 11.0-12.2%) who reported receiving a brief intervention, 5.1% (95% CI 4.6-5.6%) who were referred to treatment, and 5.8% (95% CI 5.4-6.3%) who received treatment. Similar patterns were observed when cascades of care were stratified by AUD severity. CONCLUSIONS Persons with AUD commonly utilize health care and are often screened about alcohol use, but few receive treatment. Healthcare settings-particularly primary care settings-represent a prime opportunity to implement AUD treatment to improve outcomes in this high-risk population.
Differences between the quality aspects of various generic and branded docetaxel formulations

Abstract Docetaxel is a widely prescribed chemotherapy drug in oncology and post expiry of its patent, the drug has been marketed as a generic by multiple manufacturers. It is also classified as a narrow therapeutic window drug. Through enhanced permeability and retention effect, polymeric micelles can passively target agents to tumor tissue, thereby decreasing toxicity of the drug in normal tissue. However, various studies have raised concerns that generic docetaxel leads to greater incidences of toxicities among patients with cancer. Thus, we herein review the pharmaceutical challenges associated with different docetaxel formulations and provide insights into the dissimilarities in the quality and safety of branded and generic docetaxel formulations. Literature review reported that 90% of the generic formulations of docetaxel contain inadequate quantity of active drug and high levels of impurities. Higher amounts of solvents such as polysorbate 80 and ethanol in docetaxel formulation lead to severe toxicities such as febrile neutropenia, hematological, and cutaneous toxicities. In most of the studies, even minor changes in excipients, solvents, unbound fraction of docetaxel were associated with adverse events, while in few, the source of docetaxel remained unidentified. One study reported incidence of febrile neutropenia due to a switch in the formulation from branded to generic. The quality, safety, and efficacy of medicines will directly affect the life of patients, and therefore, use of docetaxel formulations that guarantee safety of patients are the necessity of the hour. Being an injectable anti-cancer drug, it is important to determine the consistency of the various formulations of docetaxel globally, conduct bioequivalence studies as per the regulatory standards, taking into account the permissible limits of the excipients or the presence of such unapproved excipients.
Association Between Uric Acid, Carotid Intima‐Media Thickness, and Cardiovascular Events: Prospective Results From the IMPROVE Study

Background The association between elevated serum uric acid (SUA), cardiovascular disease (CVD) risk, and carotid atherosclerosis has long been explored, and contrasting results have been reported. Therefore, the role of SUA as an independent risk factor for vascular events (VEs) and carotid atherosclerosis deserves further attention. We investigated the relationship between SUA, incident VEs, carotid intima‐media thickness (cIMT), and cIMT progression in subjects at moderate‐to‐high CVD risk. Methods and Results In the IMPROVE (IMT‐Progression as Predictors of VEs) study, 3686 participants (median age 64 years; 48% men) with ≥ 3 vascular risk factors, free from VEs at baseline, were grouped according to SUA quartiles (division points: 244–284–328 µmol/L in women, 295–336–385 µmol/L in men). Carotid‐IMT and its 15‐month progression, along with incident VEs, were recorded. A U‐shaped association between SUA and VEs was observed in men, with 2.4‐fold (P = 0.004) and 2.5‐fold (P = 0.002) increased CVD risk in the first and fourth SUA quartiles as compared with the second. Adjusted hazard ratios (HRs) for cerebro‐VEs in men were the highest (first and fourth quartile versus second: HR, 5.3, P = 0.010 and HR, 4.4, P = 0.023, respectively). SUA level was independently associated with cIMT progression in men (β = 0.068, P = 0.014). No significant association between SUA levels, CVD end points, and cIMT progression were found in women. Conclusions Both low and high SUA levels are associated with an increased risk of VEs in men at moderate‐to‐high CVD risk but not in women. Only elevated SUA levels predict cIMT progression and at a lesser but not significant extent in women.