Miracle-dz/UniFAR-FTUs huggingface dataset:
C-reactive protein as a differential biomarker of bipolar II depression versus major depressive disorder

1. The description of the samples, especially age at illness onset. The authors mentioned that all patients were drug na€ıve. Usually, it is very hard to find depressed patients, especially bipolar II patients, who have never received an antidepressant treatment before consulting in the hospital. Moreover, the authors mentioned that more than 30% of the subjects in each group had a history of suicide attempt, which suggests that the patients had probably been seen by other clinicians – and probably treated by antidepressants in the past. 2. While increased C-reactive protein (CRP) may be a trait marker for suicide attempt (Courtet et al. 2015), the authors did not report if an association between CRP levels and a history of suicide attempt had been explored in their study. 3. The healthy subjects control group was not described. It remains unclear how these controls were recruited and whether they were recruited especially for this study. This may add a bias to the interpretation of the results. The authors should have reported the agreement of the local ethical committee for healthy controls. 4. The proportion of subjects treated with fluoxetine in each group would have been useful information, as antidepressants were recently found to be associated with peripheral sub-inflammation in subjects with schizophrenia (Fond et al. 2016). This increase may also be due to other potential confounding factors, including psychological stress, childhood trauma, sleep deprivation, changes in diet (linked to microbiota disturbances) and tobacco smoking. None of these factors were been reported as confounding variables. 5. Future studies should also include Toxoplasma serological status. Toxoplasma gondii infection has been associated with bipolar disorders, but not with major depressive disorder (MDD) in a recent meta-analysis (Sutterland et al. 2015). Moreover, valproate is a strong inhibitor of T. gondii, which may contribute to its anti-inflammatory properties (Fond et al. 2013; Fond et al. 2015).
A single‐cell transcriptomic analysis reveals precise pathways and regulatory mechanisms underlying hepatoblast differentiation

How bipotential hepatoblasts differentiate into hepatocytes and cholangiocytes remains unclear. Here, using single‐cell transcriptomic analysis of hepatoblasts, hepatocytes, and cholangiocytes sorted from embryonic day 10.5 (E10.5) to E17.5 mouse embryos, we found that hepatoblast‐to‐hepatocyte differentiation occurred gradually and followed a linear default pathway. As more cells became fully differentiated hepatocytes, the number of proliferating cells decreased. Surprisingly, proliferating and quiescent hepatoblasts exhibited homogeneous differentiation states at a given developmental stage. This unique feature enabled us to combine single‐cell and bulk‐cell analyses to define the precise timing of the hepatoblast‐to‐hepatocyte transition, which occurs between E13.5 and E15.5. In contrast to hepatocyte development at almost all levels, hepatoblast‐to‐cholangiocyte differentiation underwent a sharp detour from the default pathway. New cholangiocyte generation occurred continuously between E11.5 and E14.5, but their maturation states at a given developmental stage were heterogeneous. Even more surprising, the number of proliferating cells increased as more progenitor cells differentiated into mature cholangiocytes. Based on an observation from the single‐cell analysis, we also discovered that the protein kinase C/mitogen‐activated protein kinase signaling pathway promoted cholangiocyte maturation. Conclusion: Our studies have defined distinct pathways for hepatocyte and cholangiocyte development in vivo, which are critically important for understanding basic liver biology and developing effective strategies to induce stem cells to differentiate toward specific hepatic cell fates in vitro. (Hepatology 2017;66:1387–1401).
Telomere length in psychiatric disorders: Is it more than an ageing marker?

Abstract Objectives: Psychiatric and substance-use disorders have been associated with premature biological ageing. Telomere length (TL), considered an ageing marker, has been analysed in psychiatric disorders, and to a lesser extent in substance-use disorders, with recent findings suggesting TL may be related to disease pathology. Methods: We conducted a critical and non-systematic literature search of TL studies published up to June 2016 in psychiatric and substance-use disorders, focussing on studies describing mechanisms, including studies linking telomere biology with genetic factors, stress and mitochondrial alterations (104 studies selected). Results: Patients with major depressive disorder and anxiety appear to have shorter leukocyte telomeres compared to controls. Inconclusive results are found for other psychiatric disorders and for substance-use disorders. This may be due in part to differences in medication treatment and response, as studies suggest that some psychotropic medications may modulate TL. Importantly, some studies establish a relationship between telomere machinery, stress and mitochondria function in psychiatric and substance-use disorders. Conclusions: While further longitudinal studies considering telomere genetics are needed to clarify the cause–effect link between telomeres and mitochondria function in psychiatric and substance-use disorders, the recent findings linking these biological processes suggest that telomeres may be more than ageing markers.
Closing the Home Care Case: Clinicians’ Perspectives on Family Caregiving

Focus groups revealed five inherent conflicts that affect home health care clinicians’ interactions with family caregivers: (a) Services often depend on caregivers’ participation, but the home care system does not give them formal status or consideration; (b) clinicians must balance competing priorities within a short time frame; (c) clinicians recognize that families have unmet emotional and training needs, but benefits are not designed to address them; (d) clinicians face conflicting professional roles as patient advocates and service gatekeepers; and (e) agencies reserve social work services, a key to caregiver access to community resources, for their most difficult cases. Building a more rational system will involve raising awareness about the system’s limitation, providing more training and support for caregivers and the professionals who interact with them, and aligning financial incentives with the realities of what it takes to prepare caregivers to care for patients with complex needs when formal services end.
Evidence-based health care: A survey of speech pathology practice

Evidence-based practice (EBP) is essential to providing quality health care. However, we know little about how speech pathologists seek information and what barriers exist that interfere with this process. The purpose of this report was to explore the sources of evidence that guide speech pathologists' practice and also their attitudes toward research. A questionnaire was sent to 697 speech pathologists in Victoria, Australia, asking about the sources of evidence they used to guide their practice and attitudes toward research. Fifty-four percent responded. The majority of clinicians had heard of EBP and had some idea of its meaning. They also placed a high value on research. All had access to various sources of evidence including continuing education programmes, journals, Internet, and clinical guidelines. Yet, clinicians indicated that they infrequently accessed these sources and that there was little to no time to do so, which are both significant barriers to EBP. We believe that clinicians value EBP and the importance of research in managing their caseloads, but there are barriers. The challenges uncovered can improve with the support of professional bodies, training programs, and employers and managers who can influence and reinforce a culture of EBP.
Determinación de la Dominancia Coronaria en Población Mestiza Colombiana: Un Estudio Anatómico Directo

Los estudios de dominancia coronaria realizados en diversos grupos poblacionales han reportado gran variabilidad. El proposito de este trabajo fue determinar la dominancia coronaria en un grupo de mestizos colombianos. Se evaluaron los corazones obtenidos de 154 cadaveres frescos obtenidos como material de autopsia. Las arterias coronarias fueron sometidas a proceso de inyeccion con resinas sinteticas e impregnadas en solucion de KOH al 15% para liberar la grasa subepicardica. Se observo dominancia coronaria derecha en el 83,7% de los especimenes cardiacos, correspondiendo la expresion mayoritaria de estos, a la dominancia moderada con el 42,8%. La circulacion balanceada se observo en el 9,2% y la dominancia izquierda en el 7,2%, con una mayor frecuencia del subgrupo II en un 3,3% de los casos. La dominancia derecha se presento con mayor frecuencia en mujeres pero no fue estadisticamente significativa (p= 0,26). La rama circunfleja fue de expresion corta en 143 corazones (92,8%) y de expresion larga en el 7,2%. La arteria coronaria derecha finalizo entre la cruz cardiaca y el margen izquierdo en el 81,8% y con menor frecuencia en el margen izquierdo en un 1,9%. El calibre de la arteria coronaria derecha en los corazones con dominancia derecha fue de 3,21 mm (SD 0,53) y en los corazones con dominancia izquierda fue de 2,67 mm (SD 0,30), existiendo una diferencia estadisticamente significativa (p= 0,0066). Hubo un predominio de la dominancia coronaria derecha de expresion moderada, arterias circunflejas cortas y arterias coronarias derechas con mayor calibre en los especimenes con dominancia derecha
Morning Hypertension Determined by Self‐Measurement at Home Predicts Left Ventricular Hypertrophy in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

This study aimed to clarify the relationship between blood pressure (BP, mm Hg) measured by patients in the morning at home and left ventricular hypertrophy (LVH), which is a strong predictor for morbidity and mortality due to cardiovascular disease in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). We recorded self‐measured morning BPs and BPs measured at hospital check‐ups (hospital BPs) in 33 patients undergoing CAPD (mean age, 64.0 years) and compared them with left ventricular mass (LVM) derived from echocardiographic examinations. The mean morning BP was 137/75, the mean hospital BP was 140/80, and the mean LVM (g/m2.7: corrected by height) was 61.8. Of the subjects, 72.7% had LVH (LVM > 51). The morning BP (systolic) was positively correlated with LVM (P = 0.0022, R = 0.508), and the hospital BP (systolic) was weakly correlated (P = 0.0534, R = 0.339). The adjusted odds ratio for LVH was significantly higher in patients with a morning BP (systolic) ≥ 135 (15.9; 95% CI, 1.3 to 198.5) than in patients with a morning BP (systolic) < 135. In conclusion, morning hypertension determined with self‐measured BP was positively correlated with LVH, therefore self BP monitoring could be a useful method to predict LVH in CAPD patients.
Sequencing the gut metagenome as a noninvasive diagnosis for advanced nonalcoholic steatohepatitis

spontaneous liver carcinogenesis often requires more than 1 year, the authors generated a genetic background that is sensitized for liver carcinogenesis through tail vein injection of PB vectors harboring Cdkn2a-sgRNA and oncogene NRAS, respectively. The authors then performed a genome-wide screen for liver tumorigenicity through injection of a genome-scale mouse CRISPR library in the PB vector. A total of 271 sgRNAs were enriched in tumors and analyzed further. Among these enriched sgRNAs, the prominent tumor suppressor gene Trp53 was targeted twice. Cdkn2b, a tumor suppressor that has not been implicated in liver cancer, was targeted by three distinct sgRNAs in several tumors. Collectively, the authors provide an efficient and rapid strategy to identify cancer-related genes in liver cancer through an in vivo CRISPR screen. Although our understanding of the molecular pathogenesis in liver cancer has improved significantly in the past 10 years, minimal efforts have been made to translate this knowledge into clinical trials. The efforts of Song et al. and Xu et al. highlight the power of in vivo CRISPR screening in identifying novel candidate genes in liver cancer. That a lot of genes identified by these studies have not previously been implicated in liver cancer warrants further study. Ultimately, CRISPR/Cas9-based in vivo screens will yield a treasure trove of novel genes relevant to liver cancer. Such genes, as identified by these approaches, may have value as potential drug targets.
Slc7a11 (xCT) protein expression is not altered in the depressed brain and system xc- deficiency does not affect depression-associated behaviour in the corticosterone mouse model

Abstract Objectives: The cystine/glutamate antiporter (system xc-) is believed to contribute to nonvesicular glutamate release from glial cells in various brain areas. Although recent investigations implicate system xc- in mood disorders, unambiguous evidence has not yet been established. Therefore, we evaluated the possible role of system xc- in the depressive state. Methods: We conducted a protein expression analysis of the specific subunit of system xc- (xCT) in brain regions of the corticosterone mouse model, Flinders Sensitive Line rat model and post-mortem tissue of depressed patients. We next subjected system xc- deficient mice to the corticosterone model and analysed their behaviour in several tests. Lastly, we subjected additional cohorts of xCT-deficient and wild-type mice to N-acetylcysteine treatment to unveil whether the previously reported antidepressant-like effects are dependent upon system xc-. Results: We did not detect any changes in xCT expression levels in the animal models or patients compared to proper controls. Furthermore, loss of system xc- had no effect on depression- and anxiety-like behaviour. Finally, the antidepressant-like effects of N-acetylcysteine are not mediated via system xc-. Conclusions: xCT protein expression is not altered in the depressed brain and system xc- deficiency does not affect depression-associated behaviour in the corticosterone mouse model.
Modeling cost‐effectiveness and health gains of a “universal” versus “prioritized” hepatitis C virus treatment policy in a real‐life cohort

We evaluated the cost‐effectiveness of two alternative direct‐acting antiviral (DAA) treatment policies in a real‐life cohort of hepatitis C virus–infected patients: policy 1, “universal,” treat all patients, regardless of fibrosis stage; policy 2, treat only “prioritized” patients, delay treatment of the remaining patients until reaching stage F3. A liver disease progression Markov model, which used a lifetime horizon and health care system perspective, was applied to the PITER cohort (representative of Italian hepatitis C virus–infected patients in care). Specifically, 8,125 patients naive to DAA treatment, without clinical, sociodemographic, or insurance restrictions, were used to evaluate the policies’ cost‐effectiveness. The patients’ age and fibrosis stage, assumed DAA treatment cost of €15,000/patient, and the Italian liver disease costs were used to evaluate quality‐adjusted life‐years (QALY) and incremental cost‐effectiveness ratios (ICER) of policy 1 versus policy 2. To generalize the results, a European scenario analysis was performed, resampling the study population, using the mean European country‐specific health states costs and mean treatment cost of €30,000. For the Italian base‐case analysis, the cost‐effective ICER obtained using policy 1 was €8,775/QALY. ICERs remained cost‐effective in 94%‐97% of the 10,000 probabilistic simulations. For the European treatment scenario the ICER obtained using policy 1 was €19,541.75/QALY. ICER was sensitive to variations in DAA costs, in the utility value of patients in fibrosis stages F0‐F3 post–sustained virological response, and in the transition probabilities from F0 to F3. The ICERs decrease with decreasing DAA prices, becoming cost‐saving for the base price (€15,000) discounts of at least 75% applied in patients with F0‐F2 fibrosis.
The influence of popular media on perceptions of personal and population risk in possible disease outbreaks

Infectious disease outbreaks are uncertain and potentially risky events that often attract significant media attention. Previous research has shown that, regardless of their objective severity, diseases receiving greater coverage in the media are considered to be more serious and more representative of a disease than those receiving less coverage. This study assesses the role of media coverage in estimations of population risk (measured as perceived incidence among a specific population within a 1-year time period) and personal risk (measured as perceived personal likelihood of infection). Diseases with higher media coverage were considered more serious and more representative of a disease, and estimated to have lower incidence, than diseases less frequently found in the media. No difference in estimates of personal risk was found. A significant correlation between estimates of population and personal risk was found for diseases infrequently reported in the media. A weaker correlation between estimates of population and personal risk was found for diseases frequently reported in the media. The correlation remained unchanged when participants were exposed to additional information, including symptoms, mortality and estimates of prevalence.
Preservation of Long‐term Renal Allograft Survival: A Challenge for the Years to Come

In response to the letter from Drs. Hariharan and Stablein, commenting on our manuscript entitled “Long term renal allograft survival: Have we made significant progress or do we need to rethink our analytic and therapeutic strategies? ” (1), we would like to reemphasize the point that, in this paper we presented actuarial survival data, as opposed to projections that were presented in the analysis by Hariharan et al. (2). Thus, differences in methodology of half-life projections, as cited in Hariharan’s letter, have no bearing on the results and conclusions from our analysis, because we did not use projections (1).
Epigenetic regulation of hepatitis B virus covalently closed circular DNA: Implications for epigenetic therapy against chronic hepatitis B

Hepatitis B virus (HBV) infection represents a significant public health burden worldwide. Although current therapeutics manage to control the disease progression, lifelong treatment and surveillance are required because drug resistance develops during treatment and reactivations frequently occur following medication cessation. Thus, the occurrence of hepatocellular carcinoma is decreased, but not eliminated. One major reason for failure of HBV treatment is the inability to eradicate or inactivate the viral covalently closed circular DNA (cccDNA), which is a stable episomal form of the viral genome decorated with host histones and nonhistone proteins. Accumulating evidence suggests that epigenetic modifications of cccDNA contribute to viral replication and the outcome of chronic HBV infection. Here, we summarize current progress on HBV epigenetics research and the therapeutic implications for chronic HBV infection by learning from the epigenetic therapies for cancer and other viral diseases, which may open a new venue to cure chronic hepatitis B. (Hepatology 2017;66:2066–2077)
Peripheral Refraction, Peripheral Eye Length, and Retinal Shape in Myopia

Purpose To investigate how peripheral refraction and peripheral eye length are related to retinal shape. Methods Relative peripheral refraction (RPR) and relative peripheral eye length (RPEL) were determined in 36 young adults (M +0.75D to −5.25D) along horizontal and vertical visual field meridians out to ±35° and ±30°, respectively. Retinal shape was determined in terms of vertex radius of curvature Rv, asphericity Q, and equivalent radius of curvature REq using a partial coherence interferometry method involving peripheral eye lengths and model eye raytracing. Second-order polynomial fits were applied to RPR and RPEL as functions of visual field position. Linear regressions were determined for the fits’ second order coefficients and for retinal shape estimates as functions of central spherical refraction. Linear regressions investigated relationships of RPR and RPEL with retinal shape estimates. Results Peripheral refraction, peripheral eye lengths, and retinal shapes were significantly affected by meridian and refraction. More positive (hyperopic) relative peripheral refraction, more negative RPELs, and steeper retinas were found along the horizontal than along the vertical meridian and in myopes than in emmetropes. RPR and RPEL, as represented by their second-order fit coefficients, correlated significantly with retinal shape represented by REq. Conclusions Effects of meridian and refraction on RPR and RPEL patterns are consistent with effects on retinal shape. Patterns derived from one of these predict the others: more positive (hyperopic) RPR predicts more negative RPEL and steeper retinas, more negative RPEL predicts more positive relative peripheral refraction and steeper retinas, and steeper retinas derived from peripheral eye lengths predict more positive RPR.
Lid Wiper Epitheliopathy in Soft Contact Lens Wearers

Purpose To evaluate lid wiper epitheliopathy (LWE) in soft contact lens (SCL) wearers on initial presentation and after using various SCL and solution combinations. Methods LWE was assessed in 253 habitual SCL wearers who attended a screening visit at one of three study sites. LWE was assessed using lissamine green and sodium fluorescein dyes (Korb scale); a final LWE grade was calculated as the averaged LWE grade of the two dyes. Eligible habitual wearers continued into the four study periods, during which they wore one of three SCL types (etafilcon A, galyfilcon A, or senofilcon A) while using each of four care solutions for 10 to 14 days in randomized order. Statistical analyses were performed using linear mixed models, testing for differences in LWE for subject characteristics and between three multipurpose (MPS) test solutions (BioTrue, OPTI-FREE PureMoist, RevitaLens OcuTec) compared to a hydrogen peroxide (Clear Care) control solution. Results LWE was present in 85% of habitual SCL wearers. LWE was not different for age (p = 0.28), sex (p = 0.99), race (p = 0.34), and comfort (p = 0.38) and not correlated with refractive error (r = 0.07). LWE was lower in habitual senofilcon A wearers (least-squares (LS) mean ± SE = 0.82 ± 0.19) compared to wearers of lotrafilcon B (1.34 ± 0.20; p < 0.02), comfilcon A (1.41 ± 0.21; p < 0.01), and other (1.18 ± 0.16; p < 0.03). Two hundred three participants completed all four study solutions with their assigned lens type; LWE was not different between the MPSs compared to the peroxide control solution across lens materials, except for less LWE for BioTrue (0.88 ± 0.17) versus Clear Care for participants wearing galyfilcon A (1.11 ± 0.18; p < 0.01). Conclusions On initial presentation, LWE was present in 85% of habitual wearers and found to be independent of age, sex, race, comfort, and refractive error but dependent on habitual SCL type. There were no clinically meaningful differences in LWE between the MPSs and hydrogen peroxide solution for the three lens types studied.