Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009

Hepatocellular carcinoma (HCC) is increasingly reported in patients with nonalcoholic fatty liver disease (NAFLD). Our aim was to assess the prevalence and mortality of patients with NAFLD‐HCC. We examined Surveillance, Epidemiology and End Results (SEER) registries (2004‐2009) with Medicare‐linkage files for HCC, which was identified by the International Classification of Diseases for Oncology, third edition codes using topography and morphology codes 8170‐8175. Medicare‐linked data was used to identify NAFLD, hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholic liver disease (ALD), and other liver disease using International Classification of Diseases, Ninth Revision, Clinical Modification codes. NAFLD was also defined by clinical diagnosis (cryptogenic cirrhosis, obese‐diabetics with cryptogenic liver disease). A logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of HCC. In addition, adjusted hazard ratios for 1‐year mortality were estimated by Cox's proportional hazard regression. A total of 4,929 HCC cases and 14,937 controls without HCC were included. Of the HCC cases, 54.9% were related to HCV, 16.4% to ALD, 14.1% to NAFLD, and 9.5% to HBV. Across the 6‐year period (2004 to 2009), the number of NAFLD‐HCC showed a 9% annual increase. NAFLD‐HCC were older, had shorter survival time, more heart disease, and were more likely to die from their primary liver cancer (all P < 0.0001). Of those who received a transplant after HCC (n = 488), only 5% were related to NAFLD‐HCC. In multivariate analysis, NAFLD increased the risk of 1‐year mortality (OR, 1.21; 95% CI: 1.01‐1.45). Additionally, older age, lower income, unstaged HCC increased risk of 1‐year mortality while receiving a liver transplant (LT), and having localized tumor stage were protective (all P < 0.05). Conclusions: NAFLD is becoming a major cause of HCC in the United States. NAFLD HCC is associated with shorter survival time, more advanced tumor stage, and lower possibility of receiving a LT. (Hepatology 2015;62:1723–1730)
Dissecting the role of epidermal growth factor receptor catalytic activity during liver regeneration and hepatocarcinogenesis

Different data support a role for the epidermal growth factor receptor (EGFR) pathway during liver regeneration and hepatocarcinogenesis. However, important issues, such as the precise mechanisms mediating its actions and the unique versus redundant functions, have not been fully defined. Here, we present a novel transgenic mouse model expressing a hepatocyte‐specific truncated form of human EGFR, which acts as negative dominant mutant (ΔEGFR) and allows definition of its tyrosine kinase–dependent functions. Results indicate a critical role for EGFR catalytic activity during the early stages of liver regeneration. Thus, after two‐thirds partial hepatectomy, ΔEGFR livers displayed lower and delayed proliferation and lower activation of proliferative signals, which correlated with overactivation of the transforming growth factor‐β pathway. Altered regenerative response was associated with amplification of cytostatic effects of transforming growth factor‐β through induction of cell cycle negative regulators. Interestingly, lipid synthesis was severely inhibited in ΔEGFR livers after partial hepatectomy, revealing a new function for EGFR kinase activity as a lipid metabolism regulator in regenerating hepatocytes. In spite of these profound alterations, ΔEGFR livers were able to recover liver mass by overactivating compensatory signals, such as c‐Met. Our results also indicate that EGFR catalytic activity is critical in the early preneoplastic stages of the liver because ΔEGFR mice showed a delay in the appearance of diethyl‐nitrosamine‐induced tumors, which correlated with decreased proliferation and delay in the diethyl‐nitrosamine‐induced inflammatory process. Conclusion: These studies demonstrate that EGFR catalytic activity is critical during the initial phases of both liver regeneration and carcinogenesis and provide key mechanistic insights into how this kinase acts to regulate liver pathophysiology. (Hepatology 2016;63:604–619)
Predicting Success and Reducing the Risks When Attempting Vaginal Birth After Cesarean

The goal of this manuscript is to review the contemporary evidence on issues pertinent to improving the safety profile of vaginal birth after cesarean (VBAC) attempts. Patients attempting VBAC have success rates of 60%–80%, and no reliable method of predicting VBAC failure for individual patients exists. The rate of uterine rupture in all patients ranges from 0.7% to 0.98%, but the rate of uterine rupture decreases in patients with a prior vaginal delivery. In fact, in patients with a prior vaginal delivery, VBAC appears to be safer from the maternal standpoint than repeat cesarean. Inevitably, the obstetrician today will encounter the situation of deciding whether or not to induce a patient with a uterine scar, and particular attention is paid to the success and risks of inducing labor in this patient population. Induction of labor is associated with a slightly lower successful vaginal delivery rate, although the rate remains above 50% in virtually all patient populations. The rate of uterine rupture increases slightly, but still remains around 2%–3%. Although misoprostol use is discouraged due to its association with increased risks of uterine rupture, transcervical catheters, oxytocin, and amniotomy may be used to induce labor in women attempting VBAC. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to summarize recent literature regarding vaginal birth after cesarean and list factors related to labor induction success among women with a history of cesarean delivery.
Wrist Sonography Versus Electrophysiologic Studies in Diagnosis of Carpal Tunnel Syndrome

ObjectivesThe carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and is caused by the compression of median nerve at the wrist. Electrophysiologic studies are reliable diagnostic tests for CTS diagnosis. The objective of this study was to compare the diagnostic value of sonography and electrophysiologic studies in the diagnosis of CTS. MethodsThis cross-sectional study was conducted on 100 wrists of 50 consecutive patients referred to 22-Bahman Hospital with suspected diagnosis of CTS during 2007 to 2008. The patients suspicious for CTS were referred for electrophysiologic studies. Then immediately the patients underwent sonography of the median nerve. ResultsFrom the 100 wrists (50 patients) studied, CTS was diagnosed in 53 cases. Most of the cases were in females (91%) of them 90% were homemakers. The peak age distribution was in the range of 40 to 49 years. The chief complaint in all cases was pain and paresthesia. There was no predisposing factor for most cases; however, 6% were affected by diabetes, 6% by hypertriglyceridemia, and 2% by hypothyroidism. The Tinel test and Phalen test were positive in 31% and 33% of the cases, respectively, and 42% of the cases were positive for both or one of the Tinel and Phalen tests. Comparison of the ultrasonography and electrophysiologic findings showed a sensitivity of 90%, specificity of 74%, and accuracy of 83% for ultrasound in CTS diagnosis. ConclusionsThe study findings indicated an accuracy of 77% for clinical tests and 83% for sonography against electrophysiologic studies as the gold standard. Considering the acceptable sensitivity and specificity of ultrasonography, it can be recommended as a noninvasive method for diagnosis of CTS.
The HPV Vaccines—Which to Prefer?

This review presents an unbiased comparison between the two vaccines available against human papillomavirus (HPV). We conducted a PUBMED and Google search for the years 1998 to October 2008 using the terms: cervical cancer vaccine, HPV vaccine, Gardasil, and Cervarix; and also reviewed abstracts from international meetings. Both vaccines are intended to protect against cervical cancer and high-grade CIN caused by HPV 16 and HPV 18. Only the quadrivalent vaccine is designed to prevent condylomata acuminata and low-grade CIN caused by HPV 6 and HPV 11. It has been approved by the FDA for women aged 9 to 26 years against vulvar and vaginal cancer, and against cervical cancer and precancer. The adjuvant of the bivalent vaccine more significantly accelerates an immune reaction. Both vaccines demonstrate cross-protection, although against different HPV types. The bivalent vaccine is registered for above age 26 in Australia and Israel, and the quadrivalent vaccine in the Philippines and Ecuador. Time will verify claims and reveal differences. In the meantime, both vaccines are safe and effective for their approved indications and, recommendations should be based on individual patient characteristics. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to describe the viral targets of the two HPV vaccines, explain the potential benefits of HPV vaccination to patients, and compare the data regarding the two HPV vaccines.
Hepatocyte homeostasis for chromosome ploidization and liver function is regulated by Ssu72 protein phosphatase

Hepatocyte chromosome polyploidization is an important feature of liver development and seems to be required for response to liver stress and injury signals. However, the question of how polyploidization can be tightly regulated in liver growth remains to be answered. Using a conditional knockout mouse model, liver‐specific depletion of Ssu72 protein phosphatase was found to result in impairment in regulation of polyploidization. Interestingly, the aberrant polyploidization in Ssu72‐depleted mice was associated with impaired liver damage response and increased markers of liver injury and seemed to mimic the phenotypic features of liver diseases such as fibrosis, steatosis, and steatohepatitis. In addition, depletion of Ssu72 caused deregulation of cell cycle progression by overriding the restriction point of the cell cycle and aberrantly promoting DNA endoreplication through G2/M arrest. Conclusion: Ssu72 plays a substantial role in the maintenance of hepatic chromosome homeostasis and would allow monitoring of liver function. (Hepatology 2016;63:247–259)
Impairment of autophagosome-lysosome fusion in the buff mutant mice with the VPS33AD251E mutation

The HOPS (homotypic fusion and protein sorting) complex functions in endocytic and autophagic pathways in both lower eukaryotes and mammalian cells through its involvement in fusion events between endosomes and lysosomes or autophagosomes and lysosomes. However, the differential molecular mechanisms underlying these fusion processes are largely unknown. Buff (bf) is a mouse mutant that carries an Asp251-to-Glu point mutation (D251E) in the VPS33A protein, a tethering protein and a core subunit of the HOPS complex. Bf mice showed impaired spontaneous locomotor activity, motor learning, and autophagic activity. Although the gross anatomy of the brain was apparently normal, the number of Purkinje cells was significantly reduced. Furthermore, we found that fusion between autophagosomes and lysosomes was defective in bf cells without compromising the endocytic pathway. The direct association of mutant VPS33AD251E with the autophagic SNARE complex, STX17 (syntaxin 17)-VAMP8-SNAP29, was enhanced. In addition, the VPS33AD251E mutation enhanced interactions with other HOPS subunits, namely VPS41, VPS39, VPS18, and VPS11, except for VPS16. Reduction of the interactions between VPS33AY440D and several other HOPS subunits led to decreased association with STX17. These results suggest that the VPS33AD251E mutation plays dual roles by increasing the HOPS complex assembly and its association with the autophagic SNARE complex, which selectively affects the autophagosome-lysosome fusion that impairs basal autophagic activity and induces Purkinje cell loss.
TMBIM6 (transmembrane BAX inhibitor motif containing 6) enhances autophagy and reduces renal dysfunction in a cyclosporine A-induced nephrotoxicity model

Cyclosporine A (CsA) is widely used as an immunosuppressor in transplantation. Previous studies reported that CsA induces autophagy and that chronic treatment with CsA results in accumulation of autophagosomes and reduced autophagic clearance. Autophagy is a prosurvival process that promotes recovery from acute kidney injury by degrading misfolded proteins produced in the kidney. In the present study, we used TMBIM6-expressing HK-2, human kidney tubular cells (TMBIM6 cells) and Tmbim6 knockout (tmbim6−/−) mice. When exposed to CsA, the TMBIM6 cells maintained autophagy activity by preventing autophagosome accumulation. With regard to signaling, PRKKA/AMPK phosphorylation and mechanistic target of rapamycin (serine/threonine kinase) complex 1 (MTORC1) expression and its downstream target TFEB (transcription factor EB), a lysosome biogenesis factor, were regulated in the TMBIM6 cells. Lysosomal activity was highly increased or stably maintained in the presence of TMBIM6. In addition, treatment of tmbim6−/− mice with CsA resulted in increased autophagosome formation and decreased lysosome formation and activity. We also found that tmbim6−/− mice were susceptible to CsA-induced kidney injury. Taken together, these results indicate that TMBIM6 protects against CsA-induced nephrotoxicity both in vitro and in vivo by inducing autophagy and activating lysosomes.
Disasters and Perinatal Health: A Systematic Review

Background. The empirical literature on the effects of disaster on pregnancy and the postpartum period is limited. The objective of this review was to examine the existing evidence on the effect of disasters on perinatal health. Methods. A systematic review was conducted by searching electronic databases (MEDLINE, EMBASE, Cinahl, PsycInfo), including literature on disasters and pregnancy outcomes (e.g., preterm birth, low birth weight, congenital anomalies), mental health, and child development. A total of 110 articles were identified, but many published reports were anecdotes or recommendations rather than systematic studies. The final review included 49 peer-reviewed studies that met inclusion criteria. Results. Studies addressing the World Trade Center disaster of September 11 and other terrorist attacks, environmental/chemical disasters, and natural disasters such as hurricanes and earthquakes were identified. Disasters of various types may reduce fetal growth in some women, although there does not appear to be an effect on gestational age at birth. Severity of exposure is the major predictor of mental health issues among pregnant and postpartum women. After a disaster, mental health of the mother may more strongly influence on child development than any direct effect of disaster-related prenatal stress. Conclusions. There is evidence that disaster impacts maternal mental health and some perinatal health outcomes, particular among highly exposed women. Future research should focus on understudied outcomes such as spontaneous abortion. Relief workers and clinicians should concentrate on the most exposed women, particularly with respect to mental health. Target Audience: Obstetricians & Gynecologists Learning Objectives: After completion of this educational activity, the obstetrician/gynecologist should be better able to compare and contrast the effects of different types of disasters (hurricanes, earthquakes, chemical spills) on pregnant and postpartum women in order to prepare for patient care in the aftermath of such disasters; differentiate the birth outcomes likely to be affected by disaster, in order to identify patients likely to be at high risk; and assess the extent to which pregnant and postpartum women are a uniquely vulnerable population after disaster, to assist in organizing care under such circumstances.
Evaluation of 7 Serum Biomarkers and Uterine Artery Doppler Ultrasound for First-Trimester Prediction of Preeclampsia: A Systematic Review

Preeclampsia (PE) affects 1% to 2% of pregnant women and is a leading cause of maternal and perinatal morbidity and mortality worldwide. The clinical syndrome of PE arises in the second half of pregnancy. However, many underlying factors including defective placentation may already be apparent in the first and early second trimester in many patients. In clinical practice, there is currently no reliable screening method in the first trimester of pregnancy with sufficient accuracy to identify women at high risk to develop PE. Early identification of high-risk pregnancy may facilitate the development of new strategies for antenatal surveillance or prevention and thus improve maternal and perinatal outcome. The aim of this systematic review was to study the literature on the predictive potential of first-trimester serum markers and of uterine artery Doppler velocity waveform assessment (Ut-A Doppler). Literature on the 7 most studied serum markers (ADAM12, f&bgr;-hCG, Inhibin A, Activin A, PP13, PlGF, and PAPP-A) and Ut-A Doppler was primarily selected. In the selected literature, a combination of these markers was analyzed, and where relevant, the value of maternal characteristics was added. Measurements of serum markers and Ut-A Doppler were performed between week 8 + 0 and 14 + 0 GA. Low levels of PP13, PlGF, and PAPP-A and elevated level of Inhibin A have been found to be significantly associated with the development of PE later in pregnancy. The detection rates of single markers, fixed at 10% false-positive rate, in the prediction of early-onset PE were relatively low, and ranged from 22% to 83%. Detection rates for combinations of multiple markers varied between 38% and 100%. Therefore, a combination of multiple markers yields high detection rates and is promising to identify patients at high risk of developing PE. However, large scale prospective studies are required to evaluate the power of this integrated approach in clinical practice. Target Audience: Obstetricians and Gynecologists, Family physicians Learning Objectives: After completion of this article, the reader should be better able to appraise the recent literature on the development of preeclampsia in the first-trimester, evaluate the predictive value of first-trimester markers and use first-trimester markers, either individually or in combination, to assess the risk of preeclampsia.
Esophageal balloon tamponade versus esophageal stent in controlling acute refractory variceal bleeding: A multicenter randomized, controlled trial

Balloon tamponade is recommended only as a “bridge” to definitive therapy in patients with cirrhosis and massive or refractory esophageal variceal bleeding (EVB), but is frequently associated with rebleeding and severe complications. Preliminary, noncontrolled data suggest that a self‐expandable, esophageal covered metal stent (SX‐ELLA Danis; Ella‐CS, Hradec Kralove, Czech Republic) may be an effective and safer alternative to balloon tamponade. We conducted a randomized, controlled trial aimed at comparing esophageal stent versus balloon tamponade in patients with cirrhosis and EVB refractory to medical and endoscopic treatment. Primary endpoint was success of therapy, defined as survival at day 15 with control of bleeding and without serious adverse events (SAEs). Twenty‐eight patients were randomized to Sengstaken‐Blakemore tube (n = 15) or SX‐ELLA Danis stent (n = 13). Patients were comparable in severity of liver failure, active bleeding at endoscopy, and initial therapy. Success of therapy was more frequent in the esophageal stent than in balloon tamponade group (66% vs. 20%; P = 0.025). Moreover, control of bleeding was higher (85% vs. 47%; P = 0.037) and transfusional requirements (2 vs 6 PRBC; P = 0.08) and SAEs lower (15% vs. 47%; P = 0.077) in the esophageal stent group. TIPS was used more frequently in the tamponade group (4 vs. 10; P = 0.12). There were no significant differences in 6‐week survival (54% vs. 40%; P = 0.46). Conclusion: Esophageal stents have greater efficacy with less SAEs than balloon tamponade in the control of EVB in treatment failures. Our findings favor the use of esophageal stents in patients with EVB uncontrolled with medical and endoscopic treatment. (Hepatology 2016;63:1957‐1967)
Autophagy proteins are not universally required for phagosome maturation

ABSTRACT Phagocytosis plays a central role in immunity and tissue homeostasis. After internalization of cargo into single-membrane phagosomes, these compartments undergo a maturation sequences that terminates in lysosome fusion and cargo degradation. Components of the autophagy pathway have recently been linked to phagosome maturation in a process called LC3-associated phagocytosis (LAP). In this process, autophagy machinery is thought to conjugate LC3 directly onto the phagosomal membrane to promote lysosome fusion. However, a recent study has suggested that ATG proteins may in fact impair phagosome maturation to promote antigen presentation. Here, we examined the impact of ATG proteins on phagosome maturation in murine cells using FCGR2A/FcγR-dependent phagocytosis as a model. We show that phagosome maturation is not affected in Atg5-deficient mouse embryonic fibroblasts, or in Atg5- or Atg7-deficient bone marrow-derived macrophages using standard assays of phagosome maturation. We propose that ATG proteins may be required for phagosome maturation under some conditions, but are not universally required for this process.