Miracle-dz/UniFAR-FTUs huggingface dataset:
Upfront surgery in patients with clinical skip N2 lung cancer based on results of modern radiological examinations.

Background Direct lymphatic drainage from a primary tumor to the right paratracheal or aortic window lymph nodes is often noted in pN2 disease. This multi-institutional retrospective study investigated the outcomes of upfront surgery in patients with clinical skip N2 disease (N2 disease without N1 disease) and a tumor in the right upper lobe or left upper segment based on results of modern radiological examinations, including positron emission tomography (PET). Methods We identified 143 patients with cN2 disease who underwent upfront surgery in 12 institutions under the Thoracic Surgery Study Group of Osaka University between January 2006 and December 2013. Among 143 patients, 94 who underwent PET were analyzed. We classified these patients into Group A (n=39; clinical skip N2 disease and a tumor in the right upper lobe or left upper segment) and Group B (n=55; other). Results The median follow-up was 56.5 months. Among the 94 patients, 50 (53.2%) had skip N2 disease and 65 (69.1%) had a tumor in the right upper lobe or left upper segment. The 5-year overall survival (OS) rates of the 94 patients with cN2 disease was 47.9%. The 5-year OS rates for the cN2pN0/1 (n=22) and cN2pN2 (n=70) groups were 74.9% and 41.2%, respectively (P=0.034). The univariate analysis of OS revealed no significant differences in age, sex, histology, carcinoembryonic antigen (CEA) level, tumor size, PET findings, and number of metastatic lymph nodes when these parameters were dichotomized. A significantly better 5-year OS rate was observed in Group A than in Group B (64.0% vs. 37.0%; P=0.039). The multivariate analysis of OS revealed that Group A was a significantly prognostic factor (P=0.030). Conclusions Patients with cN2 disease in Group A had a more favorable prognosis. Upfront surgery may be a treatment option for such selected patients with non-small lung cancer in the specific group.
Choice of the surgical approach for patients with stage I lung squamous cell carcinoma ≤3 cm.

Background We tried to explore the surgical procedures for stage I squamous cell carcinoma (SCC) with a size of ≤3 cm by using the Surveillance, Epidemiology, and End Results (SEER) database. Furthermore, we investigated the relationships between the chosen surgical option and the size of SCC. Methods In total, 1,147 patient data sets were collected from 2010 to 2011 using the SEER database. Afterwards, 849 patients with a pT1-2aN0M0 SCC with a size of ≤3 cm after a lobectomy or sublobectomy procedure were identified. Kaplan-Meier curves were conducted to compare the overall survival (OS) rates and the lung cancer-specific survival (LCSS) rates between the two surgical approaches. Cox proportional hazards regressions were performed to discover the independent risk factors for both the OS and LCSS rates. Lastly, subgroup analysis was stratified by the size of the SCC and then classified by the 8th edition T category. Results The sublobectomy procedure did not demonstrate a difference for the OS rate. Additionally, it demonstrated a worse LCSS rate when compared with a lobectomy for stage I SCC. In the subgroup analysis, a lobectomy was shown to have a better survival outcome only when the SCC was >2 and ≤3 cm. Multivariable analysis showed that a size of >2 to ≤3 cm, and an age of >60 were independently associated with poorer OS while the sublobectomy procedure and pleural invasions (PI) were related with a poorer LCSS rate. In the stratification of data for the tumor size, the cox proportional analysis still confirmed the protective effects of the lobectomy in subgroups of SCCs with sizes between >2 to ≤3 cm as well as the T1c category. Conclusions The choice of the SCC surgery can be recommended based on the tumor size. A lobectomy procedure demonstrated a better LCSS against the sublobectomy in stage I SCC. SCC with sizes of >2 to ≤3 cm could become a pretty good indicator for lobectomy, while a sublobectomy may be an adequate substitute when the SCC size is ≤2 cm, especially for patients who cannot tolerate a lobectomy. T1c category can also suggest a lobectomy instead of sublobectomy for stage I SCC patients.
Characterization of Fasiglifam-Related Liver Toxicity in Dogs

Fasiglifam, a potent and highly selective agonist of G protein-coupled receptor 40, was developed for the treatment of type 2 diabetes mellitus. However, phase III clinical programs were terminated owing to liver safety concerns. Fasiglifam-related liver toxicity was also observed in repeat-dose dog toxicology studies, characterized by granulomatous inflammation with crystal formation in the liver and/or bile ducts. These histopathological changes were not observed in rat toxicology studies. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis of dog liver sections obtained from a repeat-dose toxicology study indicated that the crystalline material in the affected dog liver contained fasiglifam and fasiglifam glucuronide (fasiglifam-G). Nonclinical mechanistic studies indicated that after 14 days of repeated oral dosing with [14C]fasiglifam at 200 mg/kg per day to dogs, the concentrations of fasiglifam and fasiglifam-G in the bile exceeded the solubility limit of these compounds in the bile (approximately 3000 µg/ml). After single oral 2- and 200-mg/kg doses administered to rats and dogs, fasiglifam and fasiglifam-G concentrations in dog bile were 5- to 10-fold higher than those in rat bile for the same dose of fasiglifam, while the bile flow rate adjusted by body weight was 4- to 8-fold lower in dogs than in rats. High fasiglifam and fasiglifam-G concentrations in dog bile together with lower bile flow rate could cause crystal formation in dog bile, resulting in secondary granulomatous inflammation in the dog liver.
The renin-angiotensin system: going beyond the classical paradigms

Thirty years ago, a novel axis of the renin-angiotensin system (RAS) was unveiled by the discovery of angiotensin-(1−7) [ANG-(1−7)] generation in vivo. Later, angiotensin-converting enzyme 2 (ACE2) was shown to be the main mediator of this reaction, and Mas was found to be the receptor for the heptapeptide. The functional analysis of this novel axis of the RAS that followed its discovery revealed numerous protective actions in particular for cardiovascular diseases. In parallel, similar protective actions were also described for one of the two receptors of ANG II, the ANG II type 2 receptor (AT2R), in contrast to the other, the ANG II type 1 receptor (AT1R), which mediates deleterious actions of this peptide, e.g., in the setting of cardiovascular disease. Very recently, another branch of the RAS was discovered, based on angiotensin peptides in which the amino-terminal aspartate was replaced by alanine, the alatensins. Ala-ANG-(1−7) or alamandine was shown to interact with Mas-related G protein-coupled receptor D, and the first functional data indicated that this peptide also exerts protective effects in the cardiovascular system. This review summarizes the presentations given at the International Union of Physiological Sciences Congress in Rio de Janeiro, Brazil, in 2017, during the symposium entitled “The Renin-Angiotensin System: Going Beyond the Classical Paradigms,” in which the signaling and physiological actions of ANG-(1−7), ACE2, AT2R, and alatensins were reported (with a focus on noncentral nervous system-related tissues) and the therapeutic opportunities based on these findings were discussed.
Plasmacytoid dendritic cells in granulomatous variant of mycosis fungoides

Granulomatous mycosis fungoides (MF) is a rare variant in which granulomas are associated with other typical signs of MF. Its prognosis is worse than that of classical MF. Plasmacytoid dendritic cells (PDCs) are a subset of interferon‐producing dendritic cells that link the innate and the adaptative immune responses. They have also been related to tolerance to certain tumors such as melanoma.
Green tea consumption is associated with lower psychological distress in a general population: the Ohsaki Cohort 2006 Study.

BACKGROUND Although green tea or its constituents might reduce psychological stress, the relation between green tea consumption and psychological distress has not been investigated in a large-scale study. OBJECTIVE Our aim was to clarify whether green tea consumption is associated with lower psychological distress. DESIGN We analyzed cross-sectional data for 42,093 Japanese individuals aged > or =40 y from the general population. Information on daily green tea consumption, psychological distress as assessed by the Kessler 6-item psychological distress scale, and other lifestyle factors was collected by using a questionnaire. We used multiple logistic regression analyses adjusted for age, sex, history of disease, body mass index, cigarette smoking, alcohol consumption, time spent walking, dietary factors, social support, and participation in community activities to investigate the relation between green tea consumption and psychological distress. RESULTS We classified 2774 (6.6%) of the respondents as having psychological distress (Kessler 6-item psychological distress scale > or =13/24). There was an inverse association between green tea consumption and psychological distress in a model adjusted for age and sex. Although the relation was largely attenuated when possible confounding factors were adjusted for, a statistically significant inverse association remained. The odds ratio (with 95% CI) of developing psychological distress among respondents who consumed >/=5 cups of green tea/d was 0.80 (0.70, 0.91) compared with those who consumed <1 cup/d. These relations persisted when respondents were stratified by social support subgroups or by activities in communities. CONCLUSION Green tea consumption was inversely associated with psychological distress even after adjustment for possible confounding factors.
How the Results of a Randomized Trial of Catheter-Directed Thrombolysis versus Anticoagulation Alone for Submassive Pulmonary Embolism Would Affect Patient and Physician Decision Making: Report of an Online Survey

The purpose is to investigate how the outcomes of a randomized controlled trial (RCT) of catheter-directed thrombolysis (CDT) versus anticoagulation alone for acute submassive PE would affect clinical decision-making. An online survey was sent to the Pulmonary Embolism Response Team Consortium members and the North American Thrombosis Forum members. Participants rated their preference for CDT on a 5-point scale in 5 RCT outcome scenarios. In all scenarios, subjects in the CDT group walked farther at 1-year than those in the anticoagulation group. A total of 83.3% of patients and 67.1% of physicians preferred CDT (score > 3) if it improved exercise capacity and did not increase bleeding. In every scenario, patients scored CDT higher than physicians (p < 0.05 for each). Bleeding and clinical deterioration were independently associated with the mean score. Patients’ age, gender, and history of PE did not influence CDT scores (p = 0.083, p = 0.071, p = 0.257 respectively). For patients, 60% > 60 years, 65.5% < 60 years, 57.1% of men, and 66.3% of women preferred CDT across scenarios. In conclusion, the majority of respondents would choose CDT if it improves long-term exercise capacity and does not increase bleeding. Patients appear to accept a higher bleeding risk than physicians if CDT improves long-term exercise capacity.
Recurrent Proliferative Glomerulonephritis With Monoclonal Immunoglobulin Deposits in Kidney Allografts Treated With Anti-CD20 Antibodies.

BACKGROUND Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a distinct form of glomerulonephritis that often recurs after kidney transplantation causing severe graft injury and often failure. METHODS We describe post transplant outcomes and response to therapy in 20 recipients with PGNMID. Evidence of PGNMID recurrence or lack thereof was determined by protocol and clinical biopsies. RESULTS Histologic recurrence (deposition of monoclonal immunoglobulin) occurred in 18 of 20 recipients (90%), a median of 7 (1 to 65) months post transplant. At diagnosis, recurrence was generally associated with mild or no clinical manifestations and often with mild glomerular morphologic changes by light microcopy. Four of the 18 patients with recurrence did not progress and were not treated. Another 4 patients with recurrences were treated with cyclophosphamide with or without plasmapheresis, and 2 of these grafts were lost from glomerulonephritis. Nine patients with recurrences were treated with anti-CD20 antibodies (rituximab) alone, resulting in improvements in estimated glomerular filtration rate (31.5 ± 16 versus 38.8 ± 13.3 mL/min/1.73 m, P = 0.011) and proteinuria (1280 [117 to 3752] versus 168 [83 to 1613] mg/24 h, P = 0.012) although complete clinical remission was rare. One graft in this later group was lost from recurrence 141 months post transplant. Posttreatment biopsies demonstrated stable or improved glomerular histology in most cases. However, PGNMID did not resolve in any case. Four patients received rituximab 4 months pretransplant to prevent recurrence. However, 3 had mild recurrences. CONCLUSIONS Rituximab treatment of early PGNMID recurrence is effective, resulting in reasonable, long-term graft survival. Whether pretransplant rituximab modifies the course of recurrence requires additional studies.
Combined Blockade of TNF-α and IL-17A Alleviates Progression of Collagen-Induced Arthritis without Causing Serious Infections in Mice

The cytokines TNF-α and IL-17A are elevated in a variety of autoimmune diseases, including rheumatoid arthritis. Both cytokines are targets of several biologic drugs used in the clinic, but unfortunately many patients are refractory to these therapies. IL-17A and TNF-α are known to mediate signaling synergistically to drive expression of inflammatory genes. Hence, combined blockade of TNF-α and IL-17A represents an attractive treatment strategy in autoimmune settings where monotherapy is not fully effective. However, a major concern with this approach is the potential predisposition to opportunistic infections that might outweigh any clinical benefits. Accordingly, we examined the impact of individual versus combined neutralization of TNF-α and IL-17A in a mouse model of rheumatoid arthritis (collagen-induced arthritis) and the concomitant susceptibility to infections that are likely to manifest as side effects of blocking these cytokines (oral candidiasis or tuberculosis). Our findings indicate that combined neutralization of TNF-α and IL-17A was considerably more effective than monotherapy in improving collagen-induced arthritis disease even when administered at a minimally efficacious dose. Encouragingly, however, dual cytokine blockade did not cooperatively impair antimicrobial host defenses, as mice given combined IL-17A and TNF-α neutralization displayed infectious profiles and humoral responses comparable to mice given high doses of individual anti–TNF-α or anti–IL-17A mAbs. These data support the idea that combined neutralization of TNF-α and IL-17A for refractory autoimmunity is likely to be associated with acceptable and manageable risks of opportunistic infections associated with these cytokines.
CPPred: coding potential prediction based on the global description of RNA sequence

Abstract The rapid and accurate approach to distinguish between coding RNAs and ncRNAs has been playing a critical role in analyzing thousands of novel transcripts, which have been generated in recent years by next-generation sequencing technology. Previously developed methods CPAT, CPC2 and PLEK can distinguish coding RNAs and ncRNAs very well, but poorly distinguish between small coding RNAs and small ncRNAs. Herein, we report an approach, CPPred (coding potential prediction), which is based on SVM classifier and multiple sequence features including novel RNA features encoded by the global description. The CPPred can better distinguish not only between coding RNAs and ncRNAs, but also between small coding RNAs and small ncRNAs than the state-of-the-art methods due to the addition of the novel RNA features. A recent study proposes 1335 novel human coding RNAs from a large number of RNA-seq datasets. However, only 119 transcripts are predicted as coding RNAs by the CPPred. In fact, almost all proposed novel coding RNAs are ncRNAs (91.1%), which is consistent with previous reports. Remarkably, we also reveal that the global description of encoding features (T2, C0 and GC) plays an important role in the prediction of coding potential.
Does Inattention and Hyperactivity Moderate the Relation Between Speed of Processing and Language Skills?

The causal role of speed of processing (SOP) in developmental language disorder (DLD) is unclear given that SOP has been implicated in other neurodevelopmental disorders such as attention‐deficit/hyperactivity disorder. This study investigated associations between SOP, language, and inattention/hyperactivity in a U.K. epidemiological cohort (N = 528). Monolingual children from a range of socioeconomic backgrounds were assessed longitudinally; at ages 5–6 (2012/2013) and 7–8 years (2014/2015). Persistent weaknesses in SOP characterized children with DLD but did not predict language longitudinally. Ratings of inattention/hyperactivity moderated the association between SOP and language, indicating that SOP deficits are particularly detrimental for language when coupled with poor attention/hyperactivity. SOP may be a shared risk factor for DLD and inattention/hyperactivity or a general marker of neurodevelopmental disorder.
IEPAD: information extraction based on pattern discovery

research in information extraction (IE) regards the generation of wrappers that can extract particular information from semi- structured Web documents. Similar to compiler generation, the extractor is actually a driver program, which is accompanied with the generated extraction rule. Previous work in this field aims to learn extraction rules from users' training example. In this paper, we propose IEPAD, a system that automatically discovers extraction rules from Web pages. The system can automatically identify record boundary by repeated pattern mining and multiple sequence alignment. The discovery of repeated patterns are realized through a data structure call PAT trees. Additionally, repeated patterns are further extended by pattern alignment to comprehend all record instances. This new track to IE involves no human effort and content-dependent heuristics. Experimental results show that the constructed extraction rules can achieve 97 percent extraction over fourteen popular search engines.
Durability of First-Line Antiretroviral Regimens in the era of Integrase Inhibitors: A Cohort of HIV-Positive Individuals in Spain, 2014–2015

Background We compared time to treatment change (TC), viral suppression (VS) and change in CD4+ T-cell counts of first-line antiretroviral regimens (ART). Methods We analysed HIV treatment-naive adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) initiating the most commonly used ART regimens from September 2014 to November 2015. We used proportional hazards models on the sub-distribution hazard to estimate sub-distribution hazard ratios (sHR) for time to TC, logistic regression to estimate odds ratios (ORs) for VS (viral load <50 copies/ml), and linear regression to assess mean differences in CD4+ T-cell changes from ART initiation. Results Among 960 individuals, tenofovir (TDF)/emtricitabine (FTC)/rilpivirine (RPV) was the most frequently prescribed regimen (24.2%), followed by elvitegravir (EVG)/cobicistat (COBI)/TDF/FTC (22.8%), abacavir (ABC)/lamivudine (3TC)/dolutegavir (DTG; 17.4%), TDF/FTC+darunavir/ritonavir (DRV/r) or darunavir/cobicistat (DRV/c; 12.1%), TDF/FTC/efavirenz (EFV; 8.8%), TDF/FTC+raltegravir (RAL; 7.7%) and TDF/FTC+DTG (7.0%). Initiating ART with TDF/FTC+DRV/r or DRV/c (adjusted sHR: 2.96; 95% CI: 1.44, 6.08), TDF/FTC/EFV (2.18; 0.98, 4.82), TDF/FTC+RAL (2.37; 1.08, 5.22) and TDF/FTC+DTG (6.34; 3.18, 12.64) was associated with a higher risk of TC compared to ABC/3TC/DTG. At 24 weeks, VS was lower in TDF/FTC+DRV/r or DRV/c (adjusted OR: 0.37, 95% CI: 0.18, 0.74) compared with ABC/3TC/DTG, and CD4+ T-cell increase was lower in patients initiating with TDF/FTC/RPV (adjusted mean difference: −75.9, 95% CI: −130.6, −21.2) compared with those who did with ABC/3TC/DTG. Conclusions Time to TC, VS and change in CD4+ T-cell counts varies by initial regimen. These differences may be useful for making decision when initiating ART.
Cell Signaling : Proteins , Pathways and Mechanisms tert-Butylhydroquinone mobilizes intracellular-bound zinc to stabilize Nrf 2 through inhibiting phosphatase activity

Chen Y, Wang S, Fu X, Zhou W, Hong W, Zou D, Li X, Liu J, Ran P, Li B. tert-Butylhydroquinone mobilizes intracellular-bound zinc to stabilize Nrf2 through inhibiting phosphatase activity. Am J Physiol Cell Physiol 309: C148–C158, 2015. First published May 20, 2015; doi:10.1152/ajpcell.00031. 2015. —The nuclear factor erythroid 2-related factor 2 (Nrf2) is required to combat increases in oxidative stress. The chemical compound tert-butylhydroquinone (tBHQ) can downregulate Kelch-like ECH-associated protein 1 (Keap1), a repressor of Nrf2, thus maintaining the stability of Nrf2. tBHQ can also increase intracellular “free” zinc in human bronchial epithelial (16HBE) cells. We aim to investigate whether the intracellular free zinc change plays a role in Nrf2 activation. tBHQ exposure dosedependently increases intracellular free zinc concentrations within 30 min in 16HBE cells by mobilizing intracellular zinc pools. Active Nrf2 and the antioxidant enzyme heme oxygenase-1 (HO-1) increase at 3 h after tBHQ treatment. Chelating intracellular free zinc with tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN) during tBHQ exposure partially abrogates the tBHQ-induced activation of Nrf2 and HO-1 expression, while Keap1 is further decreased. These results indicate that tBHQ-induced stability of Nrf2 is associated with the intracellular free zinc level. Because the activated Nrf2 is phosphorylated, the serine/threonine protein phosphatase activity, which is known to be inhibited by zinc, is assayed. The results showed that tBHQ treatment can suppress cellular protein phosphatase-2A (PP2A) and protein phosphatase-2C (PP2C) activity, which can be abrogated by adding TPEN. This finding is verified in a cell-free protein extract experiment by supplying zinc or by chelating zinc with TPEN. These results provide a novel mechanistic insight into Nrf2 activation in antioxidant enzyme induction involving zinc signaling. The increase of intracellular free zinc may be one mechanism for Nrf2 activation. The inhibition of PP2A and PP2C activity may be involved in Nrf2 phosphorylation modulation.