Miracle-dz/UniFAR-FTUs huggingface dataset:
Advances in understanding disease mechanisms and potential treatments for Crigler–Najjar syndrome

ABSTRACT Introduction: The Crigler–Najjar syndrome (CNS) is an ultra-rare recessive disorder of the liver. There is no effective cure, except for liver transplantation, a procedure with many risks and shortcomings. Thus, the development of novel therapeutic approaches is a clinical need. Areas covered: This review aims at describing potentialities and limitations of novel experimental treatments that can be applied to cure the CNS and other metabolic liver diseases. These include pharmacological and gene therapy approaches, some of them are now being applied in clinical trials of Crigler–Najjar patients. Brief descriptions of bilirubin metabolism, mechanisms of disease, and animal models are also included. Expert opinion: AAV-mediated gene therapy approaches to pediatric liver diseases are very challenging due to the potential loss of viral DNA consequent to liver growth. Novel immunomodulatory strategies are being developed that can allow re-administration of the therapeutic vector by blocking the generation of anti-AAV neutralizing antibodies. Another very promising approach is gene targeting of the therapeutic cDNA into a ‘safe-harbor locus,’ resulting in the permanent correction of the genetic defect. However, further experimentation is still required to increase safety and efficacy. The success of these approaches will result in alternative therapies to liver transplantation.
Socket Preservation using Two Types of Bone Replacement Graft Material: A Clinical Comparative Study - 6 Months

BACKGROUND : Tooth extraction typically leads to loss of alveolar bone housing in width & height. Socket preservation at the time of extraction is done to minimise crestal bone changes, thereby minimizing horizontal and vertical ridge resorption and aids in placement of implant in a favourable position for better esthetics and function. The aim of the present study is to evaluate the soft and hard tissue dimensional changes following placement of two different socket bone substitutes in Extraction Defect Sounding (EDS) classification type I and type II defects over a period of 6 months. MATERIALS AND METHODS : 20 patients (10 in each group) selected from the outpatient department of periodontics, Ragas Dental College & hospital, Chennai who are indicated for socket preservation followed by endosseous implant placement and restoration were included in the study. After obtaining the institutional review board approval and the patient’s consent socket preservation procedures were carried out on a total of 18 patients using two putty forms of graft materials. Clinical assessment of soft tissue parameters - gingival biotype, width of keratinized gingiva and mean relative position of marginal gingiva was done at baseline, 3months and 6 months. Radiographic assessment was done for changes in the marginal bone levels at the mesial, mid buccal and distal aspect at baseline and 6 months. RESULTS : In the present study gingival phenotype and width of keratinized gingiva remained the same throughout the study period. Intra-group comparison of both groups showed a statistically significant result in mean relative position of the marginal gingiva from baseline to 6 months. Intragroup analysis for group 1 (alloplast group) showed crestal bone level changes on the mesial, mid buccal & distal marginal bone from baseline to 6 months time period, whereas group 2 (allograft group) showed crestal bone level changes on the mid buccal region only for marginal bone at 6 months time period. Similarly Inter-group comparisons of soft and hard tissue parameters were not statistically significant between the groups. Histological analysis of both putty types of bone graft biomaterials reported 43-55% vital bone and remaining 57-45% percentage of residual graft with new osteoid and fibrous encapsulation. CONCLUSION : From this clinical study it can be concluded that gingival phenotype and width of keratinized gingiva were maintained throughout the study period, there was statistically significant difference in mean relative position of the marginal gingiva from baseline to 6 months within the groups. Similarly there were marginal bone level changes in both the groups at the end of study period which was also statistically significant. There is no difference between the groups for soft and hard tissue dimensional changes.
Evaluation of a rapid dipstick test (Crystal Vc®) for the diagnosis of cholera in Maiduguri, Northeastern Nigeria

Background: Cholera is a preventable diarrheal disease associated with rapidly progressing dehydration. Early detection of the causative agent, Vibrio cholerae (VC) among symptomatic patients is a key step in cholera outbreak management to minimize disease spread and mortality. Materials and Methods: We prospectively evaluated the performance of Crystal VC®, a commercially available test kit for rapid detection of VC serotypes 01 and 0139 directly from stool samples. Patients included in this study were those admitted to the cholera treatment unit from August 14, 2017, to September 20, 2017, during the cholera outbreak in Maiduguri, northeastern Nigeria. Conventional bacterial stool culture is considered the gold standard and was used as the comparator. Results: A total of 156 stool specimens were collected and tested. Compared with stool culture results, the Crystal VC® test had sensitivity (SE) of 95.1% and specificity (SP) of 59.3%. The positive and negative likelihood ratios were 2.33 and 0.08, respectively. The positive predictive value (PPV) was 81.5% while the negative predictive value (NPV) was 86.5%. There was no gender variation with respect to SE, SP, PPV, and NPV. Conclusion: The cholera rapid dispstick test (RDT), Crystal VC®, is a useful tool for diagnosis of diarrheal disease due to VC serotypes 01 and 0139 and may provide an initial alert in an outbreak situation. It may also be used for case surveillance in cholera epidemic prone situations resulting from displacement to camps or overcrowded shelters due to human conflict or natural disasters. Although it is less sensitive than conventional stool culture, it is a convenient and simple test to perform with faster turnaround time.
Answer Quality Evaluation in Online Health Care Community

Nowadays, through the online health care community platform, users can raise health related questions and doctors would provide corresponding answers. However, some answers could be low-quality and repeated. In this paper, we aim to evaluate and predict the quality of the answers in online health care communities. We set the evaluation rules and scoring model for the medical answer text. 12 features are proposed to represent the answer quality. 8 classic classification models are used to predict the answer score. The best model gets 0.90 f1-score. Furthermore, we utilize our model to select QA data of high quality, which help the QA matching task and promote the f1-score from 0.86 to 0.93.
The Mental Health Status and Barriers to Seeking Care in Rural Women Veterans

Rural women Veterans represent a vulnerable, underserved population who encounter significant obstacles when seeking quality mental health services. However, there is a paucity of research devoted specifically to this population. To address this gap, we examined the mental health status of a group of rural women Veterans, including psychological distress, posttraumatic stress disorder (PTSD) symptoms, insomnia, suicide risk, the incidence of military sexual trauma (MST), and the perceived stigma and barriers to seeking care. One hundred and one rural Veterans interested in a women’s wellness retreat program completed written inventories. Overall, they demonstrated significant levels of psychological distress, with averages ranging between the 82nd and 88th percentiles for depression, anxiety, and somatization symptoms. In addition, 35% scored above the clinical screening level for general distress, 40% reported symptoms above the cutoff level for probable PTSD, and 70% demonstrated clinical levels of insomnia. Notably, 36% of the total sample evidenced a risk for suicide, and 68% reported MST. MST was significantly associated with increased levels of psychological distress, PTSD symptoms, and suicidality. Sixty-nine percent of participants reported at least one barrier to seeking mental health services, with scheduling difficulties, distance from facilities, and internalized stigma endorsed the most frequently. The mental health status of rural women Veterans, coupled with perceived barriers and internalized stigma, underscore the urgency of developing innovative strategies to increase the accessibility and utilization of effective services for this at-risk population.
Pathways from trade to health

ABSTRACT International trade has increased over time, both in volume and as a share of gross domestic product, and international trade agreements have proliferated. This rise in trade has many potential impacts on health outcomes. Trade raises living standards, allowing for greater spending on education and medical care, which improves health. However, trade may worsen intranational inequality, leading to increased stress and adverse impacts on mortality. Labor markets are affected by international trade, and the resulting changes in unemployment, working hours, and injury rates have an impact on health outcomes. Trade may induce adverse environmental impacts, such as increased pollution, leading to worsened health. Reductions in prices as a result of changes to trade policy may increase the consumption of unhealthy goods, including tobacco and processed foods, thus worsening the prevalence of noncommunicable diseases. Trade agreements may affect the ability of governments to legislate health-improving policies. Overall, international trade and trade agreements may have both positive and negative effects on health outcomes; government policy may be used to ameliorate any adverse effects of trade.
Spread of hospital-acquired infections and emerging multidrug resistant enterobacteriaceae in healthcare networks : assessment of the role of interfacility patient transfers on infection risks and control measures

La propagation des infections nosocomiales (IN), notamment liees aux bacteries multi-resistantes, au sein du reseau des hopitaux, est un grand enjeu de sante publique. L’evaluation du role joue par les transferts inter-etablissements des patients sur cette propagation pourrait permettre l’elaboration de nouvelles mesures de controle. L’identification de nouvelles mesures de controle est particulierement importante pour les bacteries resistantes aux antibiotiques comme les enterobacteries productrices de carbapenemase (EPC) pour lesquelles les possibilites de traitement sont tres limitees. L’utilisation des donnees de reseaux de contact inter-individus et de transferts inter-etablissement dans la modelisation mathematique ont rendu ces modeles plus proches de la realite. Toutefois, ces derniers restent limites a quelques milieux hospitaliers et quelques pathogenes. La these a eu pour objectifs de 1) mieux comprendre la structure des reseaux hospitaliers francais et leur impact sur la propagation des IN ; et 2) evaluer le role des transferts sur la propagation des EPC.Les reseaux hospitaliers francais sont caracterises par des flux de patients vers des hubs et par deux niveaux de communautes des hopitaux. La structure du reseau de transfert des patients presentant une IN n’est pas differente de celle du reseau general de transfert des patients. Au cours des dernieres annees, le nombre d’episode d’EPC a augmente en France et les predictions prevoient une poursuite de cette augmentation, avec des pics de saisonnalite en octobre. Ce travail a egalement montre que, depuis 2012, les transferts de patients jouent avec les annees un role de plus en plus important sur la diffusion des EPC en France. Des evenements de propagation multiple liee aux transferts sont egalement de plus en plus souvent observes.En consequence, la structure du reseau des hopitaux pourrait servir de base pour la proposition des nouvelles strategies de controles des IN en general, et des EPC en particulier. Les hopitaux tres connectes des grandes metropoles et les flux des patients entre les communautes locale et regionale doivent etre consideres pour le developpement de mesures de controle coordonnees entre etablissements de sante.
Expression of human papillomavirus oncoproteins E6 and E7 inhibits invadopodia activity but promotes cell migration in HPV‐positive head and neck squamous cell carcinoma cells

The rapid increase in the incidence of head and neck squamous cell carcinoma (HNSCC) is caused by high‐risk human papillomavirus (HPV) infections. The HPV oncogenes E6 and E7 promote carcinogenesis by disrupting signaling pathways that control survival and proliferation. Although these cancers are often diagnosed with metastases, the mechanisms that regulate their dissemination are unknown.
Effect of β-blockade on lung function, exercise performance and dynamic hyperinflation in people with arterial vascular disease with and without COPD

Introduction β Blockers are important treatment for ischaemic heart disease and heart failure; however, there has long been concern about their use in people with chronic obstructive pulmonary disease (COPD) due to fear of symptomatic worsening of breathlessness. Despite growing evidence of safety and efficacy, they remain underused. We examined the effect of β-blockade on lung function, exercise performance and dynamic hyperinflation in a group of vascular surgical patients, a high proportion of who were expected to have COPD. Methods People undergoing routine abdominal aortic aneurysm (AAA) surveillance were sequentially recruited from vascular surgery clinic. They completed plethysmographically measured lung function and incremental cardiopulmonary exercise testing with dynamic measurement of inspiratory capacity while taking and not taking β blocker. Results 48 participants completed tests while taking and not taking β blockers with 38 completing all assessments successfully. 15 participants (39%) were found to have, predominantly mild and undiagnosed, COPD. People with COPD had airflow obstruction, increased airway resistance (Raw) and specific conductance (sGaw), static hyperinflation and dynamically hyperinflated during exercise. In the whole group, β-blockade led to a small fall in FEV1 (0.1 L/2.8% predicted) but did not affect Raw, sGaw, static or dynamic hyperinflation. No difference in response to β-blockade was seen in those with and without COPD. Conclusions In people with AAA, β-blockade has little effect on lung function and dynamic hyperinflation in those with and without COPD. In this population, the prevalence of COPD is high and consideration should be given to case finding with spirometry. Trial registration number NCT02106286.
DIFFERENT EFFECT OF SHIFT WORK ON FATIGUE AND WORK RELATED STRESS IN EMERGENCY ROOM NURSES AT THE HOSPITALS IN BADUNG AND DENPASAR REGENCY, BALI, INDONESIA

Background: Shift work is a way to maintain proper health care daily at hospital. Shift work may affect fatigue level of nurse and work related stress in Emergency Room (ER) nurses. Generally there are two types of shift work, such as two and three division time a day. The three-division time shift includes 6-6-12 shift and 7-7-10 hours shift, and two-division time includes 12-12 hours shift. Lack of studies discusses about shift work on fatigue and work related stress in ER nurses.Objective: The aim of this study was to identify the differences of the effects between 6-6-12 shift, 7-7-10 shift, and 12-12 shift on fatigue and work related stress, and determine the dominant indicator influencing fatigue and work related stress in emergency nurses at the hospitals in Badung and Denpasar regency, Bali Indonesia.Methods: This was an observational analytic study with cross sectional approach. Purposive sampling was done to recruit 102 nurses from eight emergency departments at Badung and Denpasar regency. Occupational Fatigue Exhaustion Recovery (OFER) questionnaire was used to measure fatigue, and Expanded Nursing Stress Scale (ENSS) questionnaire was used to measure work related stress. Univariate analysis was used to analyze demographic characteristics of each ER. Kruskall-Wallis test with post hoc Mann Whitney were used to determine the different score of fatigue and work related stress between each group, and Structural Equation Modeling (SEM) was used to identify contribution of fatigue toward work related stress of ER nurses. Results: There were significant difference of the effect of shift work on fatigue, between 6-6-12 shift and 12-12 shift with p = 0.037, and between 7-7-10 shift and 12-12 shift with p = 0.003; and significant difference of the effect of shift work on work related stress, between 6-6-12 shift and 12-12 shift with p = 0.474, and between 7-7-10 shift and 12-12 shift with p = 0.128. SEM results show that fatigue contributed about 61% to increase work related stress in ER nurses.Conclusion: There was significant difference of the effects on fatigue between two and three-division time of shifts, and there was no difference of the effect on work related stress for each group. Fatigue statistically increased work related stress in ER nurses.
A Single Center Observational Study to Evaluate Epidemiology and Susceptibility Patterns to Antimicrobial Agents at a Tertiary Care Hospital in India

The unrestricted prescription of antibiotics by clinicians has led to an abrupt rise in antimicrobial resistance, threatening the use of major available drugs for the treatment of various infections (Zaman et al.,). Of particular concern in Asian sub-continent are The continuous change in microbial sensitivity to antimicrobial agents necessitates to have knowhow of local susceptibility patterns so as to help clinicians choose the right pathogen specific antimicrobial therapies. This retrospective study assessed the phenotypic characteristics of pathogens isolated from different clinical specimens and their susceptibility to some of second line of antibiotics like Ceftriaxone-Sulbactam-EDTA (CSE-1034), Meropenem, Piperacillin-Tazobactam (Pip/Taz) and Cefaperazone-Sulbactam used in our hospital settings. A total of 241 Gram-negative isolates from 600 patients treated for various bacterial infections during May 2017 to December 2017 were included in the study. Four antimicrobial agents (Ceftriaxone-sulbactam-EDTA, Meropenem, Piperacillin-Tazobactam and Cefaperazone-Sulbactam) have been used and extended spectrum β-lactamases (ESBL) and metallo β-lactamases (MBL) production was confirmed by double-disk synergy test. Of the 241Gram negative isolates obtained from 600 patients, 168 isolates were from Inpatient department (IPD) and 73 from Intensive care unit (ICU) patients. In IPD, the isolates were predominantly obtained from urine (52.4%) and wound (22.0%) whereas in ICU patients, the predominant specimens were respiratory (39.7%) and urine (36.9%). E. coli was detected in 41.5% of clinical specimens followed by K. pneumoniae (21.9%) and P. aeruginosa (15.4%). 65.6% of the isolates were reported beta-lactamase producers with 34.4% (83) as ESBL producers, 0.8% (2) as MBL producers and 30.3% (73) as ESBL+MBL producers. CSE-1034 had the greatest activity against both ESBL and ESBL+MBL producing isolates. ESBL isolates were sensitive to CSE-1034 (93.9%), Meropenem (83.1%), Cefaperazone-Sulbactam (61.4%) and Pip/Taz (51.8%). The susceptibility rates of ESBL/MBL producing isolates were CSE1034 (75.2%), Cefaperazone-Sulbactam (8.2%), Meropenem (5.5%), and Pip-Taz (2.7%). This retrospective data suggests that CSE-1034 can be considered as an important therapeutic option for the treatment of infections caused by both ESBL and ESBL+MBL producing Gram-negative isolates K e y w o r d s
Incidence of Non-alcoholic Fatty Liver Disease among Referral Outpatients to the Internal Medicine Clinic

Objective: Non-alcoholic fatty liver disease (NAFLD) is as silent comorbidity in many different settings including; diabetes mellitus (DM), obesity, and hyperlipidemia. In this study, we aimed to determine the incidence of NAFLD in referral outpatients to the internal medicine clinic to evaluate correlations between NAFLD in the other clinical backgrounds. Materials and Methods: We performed a cross-sectional study on 88 consecutive referral patients to the internal medicine clinic. Patients with a history of liver disease and alcohol consumption were excluded. Liver ultrasound was performed for diagnosing of NAFLD to be mild to moderate (Grade 1), or moderate to a severe degree of involvement (Grade 2). Clinical backgrounds of the patients, including history and laboratory exam tests such as age, exercise, and DM as well as lipid profile, and liver enzyme test results investigated in our study. Results: The incidence of NAFLD was 62% (40% Grade 2; 60% Grade 1). Patients with NAFLD had a higher body mass index, (30 ± 5 vs. 27 ± 4; P = 0.04). They were younger than patients who had not NAFLD (46 ± 15 vs. 58 ± 10 years; P = 0.0001). Total cholesterol level was higher in patients with NAFLD (198 ± 46 vs. 175 ± 46 mg/Dl; P = 0.03). Patients with NAFLD had higher serum alanine aminotransferase (ALT) level (50 ± 14 vs. 46 ± 15 IU/l; P = 0.0001). The aspartate aminotransferase/ALT ratio was lower in patients with NAFLD (0.8 ± 0.3 vs. 1 ± 0.2; P = 0.0001). Patients with NAFLD had sedentary lifestyle compared to those with normal liver (P = 0.001). Conclusion: More than half of the referral outpatients to the internal medicine clinic have NAFLD. It occurs in the young age population of patients and has a strong correlation with high-cholesterol level and sedentary lifestyle.
Cancer associated fibroblasts confer shear resistance to circulating tumor cells during prostate cancer metastatic progression

Previous studies have demonstrated that CTCs do not travel in the bloodstream alone, but rather are accompanied by clusters of stromal cells such as cancer associated fibroblasts (CAFs). Our laboratory has confirmed the presence of CAFs in the peripheral blood of prostate cancer (PC) patients. The observation that CAFs disseminate with CTCs prompts the examination of the role of CAFs in CTC survival under physiological shear stress during the dissemination process using a clinically relevant, three-dimensional (3D) co-culture model. In this study, we found that “reactive CAFs” induce shear resistance to prostate tumor cells via intercellular contact and soluble derived factors. In addition, these reactive CAFs conserve the proliferative capability of tumor cells in the presence of high magnitude fluid shear stress (FSS). This reactive CAF phenotype emerges from normal fibroblasts (NF), which take on the CAF phenotype when co-cultured with tumor cells. The reactive CAFs showed higher expression of α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP) compared to differentiated CAFs, when co-cultured with PC cells at the same experimental conditions. Together, we found that the activation mechanism of NF to CAF comprises different stages that progress from a reactive to quiescent cellular state in which these two states are differentiated by the fluctuation of intensity in CAF markers. Here we determined that a reactive state of CAFs proved to be important for supporting tumor cell survival and proliferation. These findings suggest the use of CAFs as a marker for cancer progression and a potential target for novel cancer therapeutics to treat metastatic disease.