Miracle-dz/UniFAR-FTUs huggingface dataset:
Thalamic and cerebellar hypoperfusion in single photon emission computed tomography may differentiate multiple system atrophy and progressive supranuclear palsy

Abstract Neuroimaging in the context of examining atypical parkinsonian tauopathies is an evolving matter. Positron emission tomography and single photon emission computed tomography (SPECT) bring tools, which may be reasonable in supplementary examination, however, cannot be interpreted as a criterion standard for correct diagnosis. The aim of this observational study was to assess the differentiating potential of perfusion SPECT in 3 types of atypical parkinsonisms: multiple system atrophy parkinsonian type (MSA-P), corticobasal syndrome (CBS), and progressive supranuclear palsy (PSP). The study was carried out using the comparison of standard deviations of perfusion in patients from these 3 groups. Data obtained from 10 patients with clinical diagnosis MSA-P, 14 patients with CBS and 21 patients with PSP, which were analyzed using Tukey honest significant difference post-hoc test, revealed significant differences of perfusion P < . 05 between MSA-P and PSP within the cerebellum and thalamus. No significant differences between CBS and PSP were observed.
Return to bowel screening after a false-positive faecal immunochemical test in BowelScreen (the National Bowel Screening Programme in Ireland)

Objective Little research exists on what predicts individual return to screening after a false-positive faecal immunochemical test in a population bowel screening programme. We aimed to quantify the impact of false-positive faecal immunochemical test in the first round of screening on re-attendance in BowelScreen, the National Bowel Screening Programme in Ireland. Methods A retrospective cohort study was conducted. False-positivity was defined as a positive faecal immunochemical test with subsequent colonoscopy showing no evidence of malignancy or surveillance requirement. In those with a false-positive faecal immunochemical test, logistic regression was used to predict repeat participation in the second round. Results Of 196,149 individuals who attended the first screening round, 108,075 were eligible and re-invited in the second round, and 93,971 accepted the invitation (86.9%). Second round uptake was higher in faecal immunochemical test-negative individuals compared with those having false-positive results (87.5% vs. 73.1%; p < 0.001). Older age (odds ratio (OR) 0.75; 95% confidence interval (CI) 0.60–0.94), computed tomography colonography (unsuitability/failed colonoscopy) (OR 0.40; 95% CI 0.21–0.73), and longer duration from screening invitation to faecal immunochemical test result (OR 0.991; 95% CI 0.9872–0.995) were predictors of non-re-attendance in the next screening round. Conclusion There is a significant reduction in re-attendance rates for individuals with false-positive faecal immunochemical test results. The letter sent following a negative colonoscopy is being reviewed to ensure that it provides adequate encouragement to re-attend. There are roles for screening promotion and for Gastroenterologists and Advanced Nurse Practitioners to emphasize the importance of regular faecal immunochemical tests after a negative colonoscopy.
Head-neck rotational movements using DidRen laser test indicate children and seniors’ lower performance

Sensorimotor control strategies during cervical axial rotation movements have been previously explored in narrow age ranges but never concurrently in Children and Seniors during a well-standardized task. However, the lifespan developmental approach provides a framework for research in human sensorimotor control of the head-neck complex. A cross-sectional design was used to investigate the influence of age on head-neck dynamic performance adopted by asymptomatic Children, Adults and Seniors using a standardized task (DidRen Laser test). Participants performed 5 cycles of left/right head-neck complex fast rotational movements toward 3 targets with 30° of angular separation. Dynamic performances were computed from total execution time of the test and kinematic variables derived from rotational motion of head measured by an optoelectronic system. Eighty-one participants, aged 8–85 yrs, were stratified in four groups: Children, Younger adults, Older adults and Seniors. Children were significantly slower than Younger (p<0.001) and Older adults (p<0.004) and Seniors slower than Younger adults (p<0.017) to perform the test. Children adopted a lower average speed compared to Younger (p<0.001) and Older adults (p<0.008). Children reached the peaks speed significantly later than Younger (p<0.004) and Older adults (p<0.04) and acceleration significantly later than Younger (p<0.001) and Older adults (p<0.013). From the peak acceleration, Children reached end of the cycle significantly slower than Younger (p<0.008) and Older adults (p<0.008). Children significantly differed from all other groups for rotational kinetic energy, with smaller values compared to Younger adults (p<0.001), Older adults (p<0.005) and Seniors (p<0.012). Variability was also significantly higher for Seniors and Children. In conclusion, age influences head-neck visually elicited rotational dynamics, especially in Children. These results suggest that age should be taken into account when establishing normative data and assessing dynamic head-neck sensorimotor control of patients with neck pain.
Doenjang, A Korean Traditional Fermented Soybean Paste, Ameliorates Neuroinflammation and Neurodegeneration in Mice Fed a High-Fat Diet

Obesity is considered a risk factor for neurodegeneration. Because fermentation of soybean increases contents of various bioactive compounds with anti-obesity and anti-diabetic activities, we investigated the protective effect of doenjang, a Korean traditional fermented soybean paste, against neuroinflammation and neurodegeneration in the cortex and hippocampus of mice fed a high-fat (HF) diet. C57BL/6J mice were fed a low-fat diet, an HF diet, an HF-containing steamed soybean diet, or an HF-containing doenjang (DJ) diet for 11 weeks. Doenjang consumption alleviated hippocampal neuronal loss, which was increased by the HF diet. Accordingly, we observed higher cell proliferation and neurotrophic factor mRNA levels in the DJ group. Contents of oxidative metabolites and mRNA levels of oxidative stress- and neuroinflammation-related genes were lower in the DJ group compared to the HF group. Dietary doenjang reduced β-amyloid peptide (Aβ) levels by regulating gene expressions involved in Aβ production and degradation. Furthermore, doenjang consumption reduced tau hyperphosphorylation induced by HF feeding. Overall, doenjang was more effective than steamed soybean in suppressing neuroinflammation and neurodegeneration in mice fed an HF diet. These results suggest that bioactive compounds produced during the fermentation and aging of soybean may be involved in the enhanced neuroprotective effects of doenjang.
Modulation of the TPH 1 / MAO-A / 5 HT / 5 HTR 2 A / 2 B / 2 C Axis Regulates Biliary Proliferation and Liver Fibrosis During Cholestasis

Serotonin (5HT) is a neuroendocrine hormone synthetized in the central nervous system (SNS) as well as enterochromaffin cells of the gastrointestinal tract. Tryptophan hydroxylase (TPH1) and monoamine-oxidase (MAO-A) are the key enzymes for the synthesis and catabolism of 5HT, respectively. Previous studies demonstrated that 5HTR1A/1B receptor agonists inhibit biliary hyperplasia in BDL rats, whereas 5HTR2B receptor antagonists A cc ep te d A rt ic le This article is protected by copyright. All rights reserved. attenuate liver fibrosis in mice. Aim: to evaluate the role of 5HTR2A/2B/2C agonists/antagonists in cholestatic models. Approach/Results: While in vivo studies were performed in bile duct ligated (BDL) rats and the Mdr2 mouse model of PSC, in vitro studies were performed in cell lines of cholangiocytes and hepatic stellate cells (HSCs). 5HTR2A/2B/2C and MAO-A/TPH1 are expressed in cholangiocytes and HSCs from BDL rats and Mdr2 mice. Ductular reaction, liver fibrosis as well as the mRNA expression of pro-inflammatory genes increased in normal, BDL rats and Mdr2 mice following treatment 5HTR2A/2B/2C agonists, but decreased when BDL rats and Mdr2 mice were treated with 5HTR2A/2B/2C antagonists compared to BDL rats and Mdr2 mice, respectively. 5HT levels increase in Mdr2 mice and in PSC human patients compared to their controls and decrease in serum of Mdr2 mice treated with 5HTR2A/2B/2C antagonists compared to untreated Mdr2 mice. In vitro, cell lines of murine cholangiocytes and human HSCs express 5HTR2A/2B/2C, and MAO-A/TPH1; treatment of these cell lines with 5HTR2A/2B/2C antagonists or TPH1 inhibitor decreased 5HT levels as well as the expression of fibrosis and inflammation genes compared to controls. Conclusion: Modulation of the TPH1/MAOA/5HT/5HTR2A/2B/2C axis may represent a novel therapeutic approach for the management of cholangiopathies including PSC.
Autophagy genes in myeloid cells counteract IFNγ-induced TNF-mediated cell death and fatal TNF-induced shock

Significance Sepsis is a multifactorial syndrome with increasing incidence and significant mortality. While previous work implicated tumor necrosis factor (TNF)-induced cell death in sepsis, a role for interferon-gamma (IFNγ), which synergizes with TNF to activate macrophages, is incompletely understood. We demonstrate using genome-wide CRISPR/Cas9 screening that genes regulating the cytosolic degradative pathway of autophagy protect against IFNγ-induced cell death. This cell death requires TNF and its receptor and depends on the downstream cell death mediators caspase-8 and RIPK1. Moreover, mice with myeloid cell autophagy gene deficiency are hypersusceptible to fatal TNF-induced shock, which also depends on IFNγ signaling and RIPK1. These findings identify autophagy genes as important regulators of IFNγ- and TNF-mediated cell death with implications for fatal systemic inflammatory responses. Host inflammatory responses must be tightly regulated to ensure effective immunity while limiting tissue injury. IFN gamma (IFNγ) primes macrophages to mount robust inflammatory responses. However, IFNγ also induces cell death, and the pathways that regulate IFNγ-induced cell death are incompletely understood. Using genome-wide CRISPR/Cas9 screening, we identified autophagy genes as central mediators of myeloid cell survival during the IFNγ response. Hypersensitivity of autophagy gene-deficient cells to IFNγ was mediated by tumor necrosis factor (TNF) signaling via receptor interacting protein kinase 1 (RIPK1)- and caspase 8-mediated cell death. Mice with myeloid cell-specific autophagy gene deficiency exhibited marked hypersensitivity to fatal systemic TNF administration. This increased mortality in myeloid autophagy gene-deficient mice required the IFNγ receptor, and mortality was completely reversed by pharmacologic inhibition of RIPK1 kinase activity. These findings provide insight into the mechanism of IFNγ-induced cell death via TNF, demonstrate a critical function of autophagy genes in promoting cell viability in the presence of inflammatory cytokines, and implicate this cell survival function in protection against mortality during the systemic inflammatory response.
How different are COPD-specific patient reported outcomes, health status, dyspnoea and respiratory symptoms? An observational study in a working population

Objectives We hypothesised that chronic obstructive pulmonary disease (COPD)-specific health status measured by the COPD assessment test (CAT), respiratory symptoms by the evaluating respiratory symptoms in COPD (E-RS) and dyspnoea by Dyspnoea-12 (D-12) are independently based on specific conceptual frameworks and are not interchangeable. We aimed to discover whether health status, dyspnoea or respiratory symptoms could be related to smoking status and airflow limitation in a working population. Design This is an observational, cross-sectional study. Participants 1566 healthy industrial workers were analysed. Results Relationships between D-12, CAT and E-RS total were statistically significant but weak (Spearman’s correlation coefficient=0.274 to 0.446). In 646 healthy non-smoking subjects, as the reference scores for healthy non-smoking subjects, that is, upper threshold, the bootstrap 95th percentile values were 1.00 for D-12, 9.88 for CAT and 4.44 for E-RS. Of the 1566 workers, 85 (5.4%) were diagnosed with COPD using the fixed ratio of the forced expiratory volume in one second/forced vital capacity <0.7, and 34 (2.2%) using the lower limit of normal. The CAT and E-RS total were significantly worse in non-COPD smokers and subjects with COPD than non-COPD never smokers, although the D-12 was not as sensitive. There were no significant differences between non-COPD smokers and subjects with COPD on any of the measures. Conclusions Assessment of health status and respiratory symptoms would be preferable to dyspnoea in view of smoking status and airflow limitation in a working population. However, these patient-reported measures were inadequate in differentiating between smokers and subjects with COPD identified by spirometry.
Eliminating the misconceptions about image formations in plane mirrors by conceptuL change texts

By exploring the Science Teacher program students’ misconceptions, this study was aimed to eliminate their misconceptions about image formation in plane mirrors by conceptual change texts. The data were obtained by applying a three-tired multiple choice test. The sample of the study were 90 sophomore students studying in Agri Ibrahim Cecen University Faculty of Education, Science Education Department. The conceptual change texts were then prepared to apply for instructional method in experimental group. By being parallel to each other conceptual change text method for experimental group and traditional lecturing method for control group were applied respectively. Later the multiple choice test were applied as post-test in both experimental and control group. The study showed that the conceptual change texts were more effective than traditional method for instruction to eliminate students’ misconceptions about image formation in plane mirrors.
Ubiquitous Yet Unclear: A Systematic Review of Medical Mistrust

Abstract Peer-reviewed articles (n = 124) examining associations between medical mistrust (MM) and health outcomes from four databases, between January 1998 and May 2018, were reviewed; 36 qualitative and 88 quantitative studies met the inclusion criteria. The Williams and Mohammed framework guided our narrative synthesis of the studies; it argues that basic causes (e.g., biased institutions) affect the social status of marginalized groups which in turn effects multiple proximal pathways leading to responses and poor health. Most studies were cross-sectional with US-based samples. The MM in qualitative studies were categorized as interpersonal (n = 30), systemic (n = 22), and/or vicarious (n = 18); 25% did not explicitly note the basic causes of MM and race/ethnicity was often confounded with socioeconomic status (SES). All but three studies discussed an association between MM and a behavior response; no study focused on an actual health outcome. Most quantitative studies used multivariate regression analyses; only 15 of the 88 utilized advanced modeling techniques (e.g., mediation). Most (75%) studies did not describe basic causes for MM and 43% utilized low income samples. MM was conceptualized as a predictor/proximal pathway (in 73 studies) associated with a variety of responses, most commonly behavioral (e.g., diminished adherence); 14 studies found an association between MM and a specific health measure. This review underscores the need for future qualitative studies to place MM central to their research questions as in-depth descriptions of MM were limited. Future quantitative studies should replicate findings using more advanced analytical strategies that examine the relationship between MM and health outcomes.
Evaluating the recent developments in palliative chemotherapy for metastatic colorectal cancer

The incidence of colorectal cancer (CRC) has increased. CRC is the third most common cancer and the fourth most common cause of cancer-related deaths in Korea. Palliative chemotherapy can be used to shrink tumors and ease symptoms caused by the cancer when cure is not possible. It is important to identify chemotherapeutic agents that can be used to effectively treat metastatic CRC (mCRC) and thus improve the survival and quality of life of patients with mCRC. This review aimed to evaluate the recent developments in palliative chemotherapy for mCRC and the biological or targeted agents used based on genetic alterations.
Prevalence of psoriasis and associated risk factors in China: protocol of a nationwide, population-based, cross-sectional study

Introduction Psoriasis is a chronic inflammatory skin disease which could lead to serious complications and increased risk of cardiovascular diseases. Psoriasis was recognised as a serious non-communicable disease with important public health impact by member states in the World Health Assembly resolution in 2014. However, data on psoriasis epidemiology are scarce worldwide, especially from low-income and middle-income countries. Only a few epidemiological studies on psoriasis have been conducted in parts of China, mostly without appropriate sampling design and data analysis. Aim This study aims to obtain the prevalence of psoriasis in China and relevant risk factors through a nationwide, population-based study with adequate statistical design. Methods and analysis This is a cross-sectional study to be conducted in 60 sites across China. A multistage, cluster random sampling design is used. Participants should have local household registration or be residing in the survey area for at least 6 months during the past year. The presence of psoriasis is ascertained independently by two certified dermatologists. If any discrepancies in the diagnosis occur, consensus will be met via discussion. All participants will be interviewed with a questionnaire to collect sociodemographic and disease information. The field survey will be implemented from October 2018 to June 2019. All statistical analyses will be conducted using survey procedures in SAS V.9. 2 software to adjust for the complex sample design. Ethics and dissemination The study has been reviewed and approved by the ethics committee of the Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College (Nanjing, China). A written informed consent will be obtained from all participants before the questionnaire survey. Findings of the study will be disseminated through publications in peer-reviewed journals.
Outpatient burden of neurological disorders: A prospective evaluation of 1500 patients

Introduction: Neurologists spend a significant amount of time in providing out-patient services. No comprehensive studies are there from India which have looked into the real burden of these common disorders in the out-patient population. This study was done to get a clear data on the burden of these disorders. Objectives: The aim of this study was to determine the incidence of various neurological disorders in the out-patient department services. Methods: The study was conducted in a tertiary care medical center. Clinical data of 1500 consecutive out-patients who attended the out-patient services were collected over a period of 2 months from December 2014 to January 2015. All patients were evaluated by a resident trainee and a senior consultant. Necessary investigations were done wherever applicable. The most probable clinical diagnosis was made after a detailed history and a thorough neurological evaluation. Age, sex, and the diagnosis were recorded and entered in an Excel sheet. Appropriate statistical methods were used for descriptive analysis. Results: Out of the 1500 patients, 766 were male and 734 were female. The most common complaints with which patients came to the outpatient services were headaches (28.6%), muscular and radicular pains (24.7%), seizures (12.7%) and hemiparesis/monoparesis (11.9%). Movement disorders, neuropathies, and nerve palsies were also present in a significant number of patients. Conclusion: The most common neurological disorders in the outpatient services are headache, neck pain, backache, fibromyalgia, stroke, epilepsy, and neuropathies. Newly joined residents should be well trained to efficiently manage these common outpatient disorders.
A Prognostic Marker in Idiopathic Sudden Sensorineural Hearing Loss: Serum Calprotectin

Objectives. Calprotectin, a protein released by neutrophils, has been used in many studies as a biomarker showing the presence of inflammation. In this study, it was aimed to investigate the relationship between serum calprotectin level and response to the treatment of idiopathic sudden sensorineural hearing loss (ISSHL). Methods. The present study is a prospective, cross-sectional historical cohort study. The study group consisted of 44 patients with ISSHL, and the control group consisted of 41 healthy volunteers without ear pathology. At the same time, patients in the study group were divided into three groups according to the response to ISSHL treatment (recovered, partially recovered, unrecovered). The relationship between the groups was statistically evaluated in terms of serum calprotectin levels. Results. The mean serum calprotectin value was 75.67±19.48 ng/mL in the study group and 50.24±29.14 ng/mL in the control group (P=0.001). Serum calprotectin value according to the severity of hearing loss in the mild, moderate and severe was 66.20±8.82, 70.35±16.77, and 91.23±19.73 ng/mL, respectively. Serum calprotectin value in the severe group was significantly higher compared to the moderate and mild groups (P=0.004, P=0.001, respectively). Serum calprotectin value according to the treatment response in the recovered, partially recovered and unrecovered groups was 63.36±11.54, 80.17±12.06, and 85.33±22.33 ng/mL, respectively. Serum calprotectin value in the recovered group was significantly lower compared to the partially recovered and unrecovered groups (P=0.002, P=0.001, respectively). Conclusion. Serum calprotectin value informs the clinician about both the severity of hearing loss and the response to treatment. Hence, serum calprotectin can be used as an important biomarker in ISSHL patients for the determination of the prognosis of disease.
Kinome profiling of non-Hodgkin lymphoma identifies Tyro3 as a therapeutic target in primary effusion lymphoma

Significance B cell-derived non-Hodgkin lymphomas (NHLs) consist of a very diverse set of malignancies. One NHL subtype, primary effusion lymphoma (PEL), has a poor prognosis with patients having a median survival time of about 6 mo postdiagnosis. By profiling the kinome of multiple B cell NHL lines, we identified several kinases uniquely upregulated in PEL compared with other subtypes, the most significant of which was Tyro3. We developed an inhibitor against Tyro3 kinase activity; this small molecule inhibitor reduced PEL survival and growth in vitro, and tumor burden in a PEL xenograft model in vivo. Our study suggests that a Tyro3 inhibitor may be beneficial in treating PEL. Non-Hodgkin lymphomas (NHLs) make up the majority of lymphoma diagnoses and represent a very diverse set of malignancies. We sought to identify kinases uniquely up-regulated in different NHL subtypes. Using multiplexed inhibitor bead-mass spectrometry (MIB/MS), we found Tyro3 was uniquely up-regulated and important for cell survival in primary effusion lymphoma (PEL), which is a viral lymphoma infected with Kaposi’s sarcoma-associated herpesvirus (KSHV). Tyro3 was also highly expressed in PEL cell lines as well as in primary PEL exudates. Based on this discovery, we developed an inhibitor against Tyro3 named UNC3810A, which hindered cell growth in PEL, but not in other NHL subtypes where Tyro3 was not highly expressed. UNC3810A also significantly inhibited tumor progression in a PEL xenograft mouse model that was not seen in a non-PEL NHL model. Taken together, our data suggest Tyro3 is a therapeutic target for PEL.