Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancing immunity against melanoma using Type I interferon

Melanoma is an aggressive cancer, which when diagnosed in the late stages has a median survival rate of 6 months. The current gold-standard for adjuvant therapy is high doses of the type I interferon (IFN)-2, which prolongs disease free survival, but not overall survival. This high-dose therapy has many serious side-effects, resulting in doses to be lowered to sub-therapeutic levels. It is not clear how IFN-2 acts to treat melanoma, however it is accepted that immune enhancement is involved. The two main type I IFN families, IFN- and IFN-, signal via the same receptor, however they have been found to be functionally different. Of the IFN- family, 13 subtypes have been discovered and there is evidence that each is functionally unique. This project explores the therapeutic efficacy of seven type I IFN subtypes, including IFN-2 and IFN-, in treating melanoma. To test efficacy, a model of DNA therapy to administer plasmids encoding the IFN subtypes was combined with a melanoma model utilizing B16 F1 cells expressing the immunogenic peptide glycoprotein B. We have found that the IFN- subtypes tested have greater efficacy than IFN-2 in treating melanoma. The IFN subtypes delayed tumour onset, and one subtype demonstrated a significant increase in survival time. In addition, therapeutic effects could be seen when sera levels were lower than that of IFN-2. The in vitro effects of the IFN subtypes on melanoma cells was examined, uncovering differences in potency. Furthermore, we have found evidence of anti-tumour immune enhancement is associated with IFN- therapy but not IFN-. This research shows that the IFN- subtypes differ in their anti-tumour efficacy, and potency of actions. Therefore the IFN- subtypes show potential as a superior therapy in treating melanoma, which may be administered at lower, less toxic doses.
Continuous norming of psychometric tests: A simulation study of parametric and semi-parametric approaches

Continuous norming methods have seldom been subjected to scientific review. In this simulation study, we compared parametric with semi-parametric continuous norming methods in psychometric tests by constructing a fictitious population model within which a latent ability increases with age across seven age groups. We drew samples of different sizes (n = 50, 75, 100, 150, 250, 500 and 1,000 per age group) and simulated the results of an easy, medium, and difficult test scale based on Item Response Theory (IRT). We subjected the resulting data to different continuous norming methods and compared the data fit under the different test conditions with a representative cross-validation dataset of n = 10,000 per age group. The most significant differences were found in suboptimal (i.e., too easy or too difficult) test scales and in ability levels that were far from the population mean. We discuss the results with regard to the selection of the appropriate modeling techniques in psychometric test construction, the required sample sizes, and the requirement to report appropriate quantitative and qualitative test quality criteria for continuous norming methods in test manuals.
Rise and Fall of the Empire: Conquering Alzheimer’s Disease by Targeting Adult Neurogenesis

Early Seizure Activity Accelerates Depletion of Hippocampal Neural Stem Cells and Impairs Spatial Discrimination in an Alzheimer’s Disease Model Fu CH, Iascone DM, Petrof I, Hazra A, Zhang X, Pyfer MS, Tosi U, Corbett BF, Cai J, Lee J, Park J, Iacovitti L, Scharfman HE, Enikolopov G, Chin J. Cell Rep. 2019;27(13):3741-3751.e4. doi:10.1016/j.celrep. 2019.05. 101. PMID:31242408. Adult hippocampal neurogenesis has been reported to be decreased, increased, or not changed in patients with Alzheimer disease (AD) and related transgenic mouse models. These disparate findings may relate to differences in disease stage, or the presence of seizures, which are associated with AD and can stimulate neurogenesis. In this study, we investigate a transgenic mouse model of AD that exhibits seizures similarly to patients with AD and find that neurogenesis is increased in early stages of disease, as spontaneous seizures became evident, but is decreased below control levels as seizures recur. Treatment with the antiseizure drug levetiracetam restores neurogenesis and improves performance in a neurogenesis-associated spatial discrimination task. Our results suggest that seizures stimulate, and later accelerate the depletion of, the hippocampal neural stem cell pool. These results have implications for AD as well as any disorder accompanied by recurrent seizures, such as epilepsy.
Does subclinical hypothyroidism and/or thyroid autoimmunity influence the IVF/ICSI outcome? Review of the literature

Abstract While overt hypothyroidism is a well-known risk factor for infertility, the association of subclinical hypothyroidism (SCH) or thyroid autoimmunity and reproductive failure has been still not elucidated. In this literature review, the current data on the effect of SCH and/or thyroid autoimmunity and human reproduction is presented. The main ART outcome measures are as follows: number of oocytes retrieved, fertilization rate, implantation rate, clinical pregnancy rate per embryo transfer, embryo quality, miscarriage rate, and live birth rate. Current guidelines on the management of women with SCH and/or thyroid autoimmunity undergoing ART cycles will be presented in this review.
No Reduction in Surgical Site Infection Obtained with Post-Operative Antibiotics in Facial Fractures, Regardless of Duration or Anatomic Location: A Systematic Review and Meta-Analysis.

Background: We performed a systematic review of the literature on antibiotic prophylaxis practices in open reduction, and internal fixation of, facial fracture(s) (ORIFfx). We hypothesized that prolonged antibiotic prophylaxis (PAP) would not decrease the rate of surgical site infections (SSIs). Methods: We performed a systematic review of four databases: PubMed, CENTRAL, EMBase, and Web of Science, from inception through January 15, 2017. Three independent reviewers extracted fracture location (orbital, mid-face, mandible), antibiotic use, SSI incidence, and time from injury to surgery. Mantel-Haenszel and generalized estimating equations were carried out independently for each fracture zone. Results: Of the 587 articles identified, 54 underwent full-text review, yielding 27 studies that met our inclusion criteria. Of these, 16 studies (n = 2,316 patients) provided data for mandible fractures, four studies (n = 439) for mid-face fractures, and six studies (n = 377) for orbital fractures. Pooled analysis of each fracture type's SSI rate showed no statistically significant association with the odds ratio (OR) of developing an SSI. For mandible fractures treated with ORIFfx, the OR for an SSI after 24-72 hours of prophylaxis relative to <24 hours was 0.85 (95% confidence interval [CI] 0.62-1.17), whereas for >72 hours compared with <24 hours, the OR was 1.42 (95% CI) 0.96-2.11). For mid-face fractures, there was no improvement in SSI rate from PAP (OR 1.05; 95% CI 0.20-5.63). Conclusions: We did not demonstrate a lower rate of SSI associated with PAP for any ORIFfx repair. Post-operative antibiotics for >72 hours paradoxically may increase the SSI risk after mandible fracture repairs.
Systematic review of the diagnostic accuracy, reliability, and safety of the sharp-purser test

ABSTRACT Introduction: The Sharp-Purser Test (SPT) is used to assess for atlantoaxial instability (AI) in patients with rheumatoid arthritis (RA). The test is commonly used by clinicians; however, many experts argue it lacks reliability and validity along with concerns of safety. The primary purpose of this review is to determine the diagnostic accuracy of the SPT to detect AI. Methods: A search of five databases was performed from inception to 19 December 2018 using search terms related to the SPT. Studies were eligible for inclusion if the SPT was used on a patient/participant. Methodological quality assessment of diagnostic studies was performed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) for studies that reported data to calculate sensitivity (SN), specificity (SP), positive likelihood ratio (+LR), and negative likelihood ratio (-LR). Results: The search yielded 1009 articles, and 32 studies met the inclusion criteria for analysis. Meta-analysis on diagnostic accuracy studies assessing the SPT was not possible due to statistical heterogeneity. Six diagnostic accuracy studies assessed the SN of the SPT ranging from 0.19 to 1.00. Four of the studies assessed SP of the SPT ranging from 0.71 to 0.98. The +LR was identified in 4 studies was 0.655, 1.73, 22, and 17.25. The -LR was 1.14, 0.799, 0.571, and 0.323. Seven RCTs utilized the SPT to screen for AI, and the SPT was used in 18 case reports. Conclusion: The SPT may be inappropriate to use due to inconsistent validity, poor inter-rater reliability, and potential to cause harm. Level of evidence: 1
Odontogenic sinusitis is a common cause of unilateral sinus disease with maxillary sinus opacification

Unilateral sinus disease (USD) carries a broader differential diagnosis than bilateral sinus disease, including various inflammatory and neoplastic conditions. Odontogenic sinusitis (ODS) is a common cause of unilateral maxillary sinusitis, but few studies have examined its incidence among all USD etiologies. The main purposes of this prospective study were to determine the incidences of ODS and other etiologies causing USD with complete maxillary sinus opacification on computed tomography (CT), and to compare CT features of ODS and non‐odontogenic USD patients. In addition, clinical features of the ODS cohort are described.
Older homeless women with depression

This qualitative descriptive study described how seven older homeless women with depression characterized their homelessness, depression, and aging. The women, with a mean age of 54 years, were concerned with day-to-day survival, and contemplating aging while remaining homeless was frightening. The women described feeling depressed and most had received treatment for depression; however they did not describe their depression as hindering their ability to find housing. The themes were aging, homelessness, depression, and chronic health conditions. Homelessness contained the subthemes of addictions, loss of relationships, and lack of income. Depression contained the subthemes of history, experience, and treatment of depression. Although chronic health conditions and chronic pain were concerns for all participants, only one woman had access to ongoing health care. The majority of the women had no income. Nearly all the women had attended school beyond high school but this did not translate into better paying employment because most of them had worked at jobs with no benefits. Implications for policy development included expanding the safety net to provide housing options for homeless women in the 50–60 year range. Recommendations for practitioners included the suggestion that older homeless women be viewed as geriatric clients with care provided at that level. Future research should explore the connection between addictions and homelessness for older homeless women, the impact of chronic pain or chronic illness on their daily functioning, and the potential benefits of treating older homeless women according to standards of care developed for the geriatric general population.
Effects of Protective American Football Headgear on Peripheral Vision Reaction Time and Visual Target Detection in Division I NCAA Football Players

The purpose of this study was to examine the effects of protective football headgear on peripheral vision reaction time and visual target detection. Twenty-five Division I NCAA football players (age = 20.5 yrs ± 0.9, height = 185.9 cm ± 6.8, body mass = 99.2 kg ± 19.2, BMI = 29.6 ± 4.5) participated. In a crossover counterbalanced study design, subjects participated in one visit with three conditions: Baseline (BL) without headgear, helmet only (HO), helmet with an eye shield (HE). Subjects completed a 1-min peripheral vision reaction time test for each condition separated by 3-min recovery periods. Tests were administered using a 64 light Dynavision D2 Visuomotor board. Target detection (total hit score) was higher during BL than HO (p < 0.001) and HE (p < 0.001). Average (p < 0.001), peak (p < 0.001), minimum (p < 0.001), and median (p < 0.001) peripheral reaction times were faster during BL than HO and HE. No significant differences were observed for any measures between HO and HE conditions (p > 0.05). Findings indicate that protective football headgear impaired reaction time to peripheral visual stimuli. The addition of an eye shield to the helmet had a small non-significant effect on reaction time and target detection. These results may hold important implications in helmet design and player safety.
Maternal viral infection causes global alterations in porcine fetal microglia

Significance Mental health disorders account for approximately 14% of the worldwide burden of disease and affect people of all age groups and socioeconomic statuses. Prenatal exposure to maternal infection increases the risk of developing certain mental health disorders, most notably schizophrenia and autism. Maternally derived cytokines, up-regulated during infection, may lead to an aberrant proinflammatory and phagocytic shift in fetal microglia, the resident immune cells of the brain. As these cells perform essential processes that aid in the highly orchestrated progression of brain development, modifications in their prenatal phenotype could be detrimental. Using swine, a highly translatable animal model, we show that fetal microglia activity is globally altered by maternal infection, a finding that could have far-reaching implications for neuropsychiatric disorders. Maternal infections during pregnancy are associated with increased risk of neurodevelopmental disorders, although the precise mechanisms remain to be elucidated. Previously, we established a maternal immune activation (MIA) model using swine, which results in altered social behaviors of piglet offspring. These behavioral abnormalities occurred in the absence of microglia priming. Thus, we examined fetal microglial activity during prenatal development in response to maternal infection with live porcine reproductive and respiratory syndrome virus. Fetuses were obtained by cesarean sections performed 7 and 21 d postinoculation (dpi). MIA fetuses had reduced brain weights at 21 dpi compared to controls. Furthermore, MIA microglia increased expression of major histocompatibility complex class II that was coupled with reduced phagocytic and chemotactic activity compared to controls. High-throughput gene-expression analysis of microglial-enriched genes involved in neurodevelopment, the microglia sensome, and inflammation revealed differential regulation in primary microglia and in whole amygdala tissue. Microglia density was increased in the fetal amygdala at 7 dpi. Our data also reveal widespread sexual dimorphisms in microglial gene expression and demonstrate that the consequences of MIA are sex dependent. Overall, these results indicate that fetal microglia are significantly altered by maternal viral infection, presenting a potential mechanism through which MIA impacts prenatal brain development and function.
Prevalence and risk factors for diabetic retinopathy in a cross-sectional population-based study from rural southern China: Dongguan Eye Study

Research question The current population-based study aimed to investigate the prevalence of diabetic retinopathy (DR) and risk factors among residents over 40 years old in the rural area of Dongguan, southern China. Study design The Dongguan Eye Study was a population-based study from September 2011 to February 2012. Setting The area was set in the rural area of Dongguan, southern China. Participants Adult rural population aged 40 or older. Intervention Participants underwent haematological, physical, ophthalmic examinations and completed a questionnaire regarding lifestyles and systemic medical conditions. Primary and secondary outcome measures The frequency and risk factors of visual impairment and the major vision-threatening eye diseases. Results Of the 8952 Han Chinese, 1500 were diagnosed with type 2 diabetes mellitus (T2DM) with an average age of 59.5±11.1 years, and 1310 participants with fundus photography results were analysed. Standardised prevalence rate of DR was 18.2% for all patients with diabetes, 32.8% for the patients with previously diagnosed diabetes and 12.6% for newly diagnosed patients with T2DM. The prevalence rate of male DR was significantly higher than that of female DR (23.0% vs 14.1%, p<0.001). No significant difference was found in age-specific prevalence of DR. In diabetic patients, the prevalence rates of vision-threatening diabetic retinopathy, diabetic macular oedema and clinically significant macular oedema were 2.5%, 2.8% and 0.9%, respectively. Male gender, higher education level, longer duration of diabetes mellitus (DM), higher systolic blood pressure and glycosylated haemoglobin were independent risk factors for DR development in patients with diabetes. Conclusion A relatively lower prevalence of DR was found among the participants with T2DM in residents over 40 years in the rural area of southern China. Thus, an ophthalmic examination is recommended, especially for individuals with DM and DR risk factors. There is a need to increase awareness and education on DM and DR, especially in subjects with DR risk factors to reduce the incidence of DR and macular oedema.
Aortic Arch Atherosclerosis in Patients With Embolic Stroke of Undetermined Source: An Exploratory Analysis of the NAVIGATE ESUS Trial.

Background and Purpose- Aortic arch atherosclerosis (AAA) is a possible source of embolism in patients with embolic stroke of undetermined source. Previous studies reported high rates of embolic events in patients with AAA, especially those with high-risk AAA. This exploratory analysis of NAVIGATE ESUS (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source) focused on patients with AAA and assessed their characteristics, stroke recurrence rates, and response to treatment. Methods- The detection of AAA and the assessment of its features were based on transesophageal echocardiography that was done in 19% of participants. AAA plaques were considered to have complex features when reported as complex or ulcerated or were ≥4 mm in thickness or had a mobile thrombus present. Results- Among 1382 participants who had transesophageal echocardiography, 397 (29%) had AAA and 112 (8%) had complex AAA. Mean (SD) age (63 [10] versus 67 [9] versus 69 [9]; P<0.001), prevalence of diabetes mellitus (19% versus 26%, versus 32%; P=0.002), and aortic valvulopathy (10 versus 20 versus 20; P<0.001) increased across no versus noncomplex versus complex AAA, respectively. In multivariable analyses, increasing age, diabetes mellitus, aortic valvulopathy, statin use before randomization, chronic infarcts on imaging, and region were independently associated with any AAA versus no AAA and also with complex AAA versus no AAA. Multiterritorial qualifying infarcts rather than single-territory infarcts were observed in 21% with complex AAA versus 17% noncomplex versus 13% no AAA (P=0.07). Annualized rates of ischemic stroke recurrence were 7.2% versus 4.2% versus 5.6% for complex versus noncomplex versus no AAA, respectively. While prevalence of complex AAA increased with increasing risk score, after adjusting for risk score, we did not observe increased risk of recurrent stroke for patients with complex AAA (hazard ratio, 1.1; 95% CI, 0.53-2.4), although the number of outcomes was limited. In patients with complex AAA, 4 strokes occurred among rivaroxaban-assigned patients and 4 strokes among aspirin-assigned patients. Conclusions- Complex AAA is prevalent in embolic stroke of undetermined source patients and is associated with atherosclerotic burden. Whether complex AAA independently increases recurrent stroke risk and whether a non-vitamin-K oral anticoagulant as compared with aspirin may be effective for reducing recurrent stroke requires additional study. Clinical Trial Registration- URL: https://www.clinicaltrials. gov. Unique identifier: NCT02313909.
Pharmacokinetic considerations for current state-of-the-art antidepressants

ABSTRACT Introduction: Nowadays, the first-line medications in depression include SSRIs, SNRIs, NDRIs, NaSSAs, SMSs, or a melatonin (M1/M2) receptor agonist and a 5-HT2C receptor antagonist. These drugs have quite similar antidepressant efficacy and safety profiles, but they differ in chemical structure, receptor affinity, and pharmacokinetics. Areas covered: Pharmacokinetic properties of first-line antidepressant drugs and factors influencing their pharmacokinetic processes are presented. Alterations in pharmacokinetics of newer antidepressants in special populations are summarized. In addition, the significance of therapeutic drug monitoring (TDM) and pharmacogenetic testing in dose optimization for the treatment of depressive disorders using newer antidepressants is discussed. Expert opinion: Due to the fact that 30-40% of depressive patients do not respond to the therapy and that the incidence of depression is constantly growing, the search for new more effective and safer antidepressant therapies is becoming an urgent need. More well-designed clinical studies under naturalistic conditions are needed to establish/refine therapeutic ranges for older and current state-of-the-art antidepressant drugs. The pharmacogenetic testing with concomitant application of TDM seems to be the best way for implementing personalized dosing of current state-of-the-art antidepressants metabolized by polymorphic CYPs, especially when co-administered with strong inhibitors or other substrates of CYP2D6 or CYP2C19.
Physical and psychosocial work exposures as risk factors for disability retirement due to a shoulder lesion

Objective To assess the longitudinal associations of physical and psychosocial exposures with disability retirement due to a shoulder lesion. Methods In a nationwide register-based study, we followed 1 135 654 wage earners aged 30–59 years for the occurrence of disability retirement due to a shoulder lesion. The occupational exposures were assessed with job exposure matrices. We used a competing risk regression model to estimate HRs and their 95% CIs and to test for the association between the exposures and the outcome. We also calculated the attributable fraction of disability retirement due to occupational exposures. Results A total of 2472 persons had full disability retirement due to a shoulder lesion during the follow-up. Physically heavy work showed the strongest association with the outcome in both genders, in men with an HR of 2.90 (95% CI 2.37 to 3.55) and in women with an HR of 3.21 (95% CI 2.80 to 3.90). Of the specific physical exposures, working with hands above shoulder level was statistically significantly associated with disability retirement in men. When all physical exposures were taken into consideration, 46% and 41% of disability retirement due to a shoulder lesion were attributed to physical work load factors in men and women, respectively. In addition, 49% (men) and 35% (women) of disability retirement were attributed to psychosocial work-related factors. Conclusions Our findings suggest that a considerable proportion of disability retirement due to a shoulder lesion could be prevented by reducing physical and psychosocial exposures at work to a low level.