Miracle-dz/UniFAR-FTUs huggingface dataset:
Association Between Pancreatic Fistula and Long-term Survival in the Era of Neoadjuvant Chemotherapy.

Importance In the past decade, the use of neoadjuvant therapy (NAT) has increased for patients with borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Data on pancreatic fistula and related overall survival (OS) in this setting are limited. Objective To compare postoperative complications in patients undergoing either upfront resection or pancreatectomy following NAT, focusing on clinically relevant postoperative pancreatic fistula (CR-POPF) and potential associations with OS. Design, Setting, and Participants This retrospective cohort study was conducted on data from patients who underwent pancreatic resection for PDAC at the Massachusetts General Hospital from January 1, 2007, to December 31, 2017. Exposures Pancreatic cancer surgery with or without NAT. Main Outcomes and Measures Overall morbidity and CR-POPF rates were compared between NAT and upfront resection. Factors associated with CR-POPF were assessed with univariate and multivariate analysis. Survival data were analyzed by Kaplan-Meier curves and a Cox proportional hazards regression model. Results Of 753 patients, 364 were men (48.3%); median (interquartile range) age was 68 (61-75) years. A total of 346 patients (45.9%) received NAT and 407 patients (54.1%) underwent upfront resection. At pathologic examination, NAT was associated with smaller tumor size (mean [SD], 26.0 [15.3] mm vs 32.7 [14.4] mm; P < .001), reduced nodal involvement (102 [25.1%] vs 191 [55.2%]; P < .001), and higher R0 rates (257 [74.3%] vs 239 [58.7%]; P < .001). There were no significant differences in severe complication rate or 90-day mortality. The rate of CR-POPF was 3.6-fold lower in patients receiving NAT vs upfront resection (13 [3.8%] vs 56 [13.8%]; P < .001). In addition, factors associated with CR-POPF changed after NAT, and only soft pancreatic texture was associated with a higher risk of CR-POPF (38.5% vs 6.3%; P < .001). Survival analysis showed no differences between patients with or without CR-POPF after upfront resection (26 vs 25 months; P = .66), but after NAT, a worse overall survival rate was observed in patients with CR-POPF (17 vs 34 months; P = .002). This association was independent of other established predictors of overall survival by multivariate analysis (hazard ratio, 2.80; 95% CI, 1.44-5.45; P < .002). Conclusions and Relevance Neoadjuvant therapy may be associated with a significant reduction in the rate of CR-POPF. In addition, standard factors associated with CR-POPF appear to be no longer applicable following NAT. However, once CR-POPF occurs, it is associated with a significant reduction in long-term survival. Patients with CR-POPF may require closer follow-up and could benefit from additional therapy.
Age Differences in Intertemporal Choice: The Role of Task Type, Outcome Characteristics, and Covariates.

OBJECTIVES Prior research has revealed age differences in the preferred timing of monetary outcomes, but results are inconsistent across studies. The present study examined the role of task type, outcome characteristics, and a range of theoretically implicated covariates that may contribute to variations in age effects. METHOD Two types of intertemporal choice paradigms (temporal discounting and sequence construction) were administered to a diverse life-span sample (n=287, aged 18-87). The design experimentally manipulated outcome delay (months versus years), amount (hundreds versus thousands), and valence (gain versus loss) while statistically controlling for a range of potential covariates including demographics, affect, personality, time perspective, subjective health, and numeracy. RESULTS In the temporal discounting task, no significant age differences were observed and this pattern did not differ by outcome delay, amount, or valence. In the sequence-construction task, age was associated with a preference for sequences of decreasing impact in the gain condition but not in the loss condition, whereas outcome delay and amount did not moderate age effects. Age patterns in discounting and sequences preferences remained unchanged after controlling for covariates. DISCUSSION These findings converge with prior studies reporting weak or null effects of age in temporal discounting tasks and suggest that inconsistent results are not due to variations in outcome valence, delay, or amount across studies. Findings also add to the scarce evidence for age differences sequence-preferences. After discussing methodological limitations, we consider implications for future research and practice.
Epigenetic Regulation of Adipogenic Differentiation by Histone Lysine Demethylation

Obesity is a rising public health problem that contributes to the development of several metabolic diseases and cancer. Adipocyte precursors outside of adipose depots that expand due to overweight and obesity may have a negative impact on human health. Determining how progenitor cells acquire a preadipocyte commitment and become mature adipocytes remains a significant challenge. Over the past several years, we have learned that the establishment of cellular identity is widely influenced by changes in histone marks, which in turn modulate chromatin structure. In this regard, histone lysine demethylases (KDMs) are now emerging as key players that shape chromatin through their ability to demethylate almost all major histone methylation sites. Recent research has shown that KDMs orchestrate the chromatin landscape, which mediates the activation of adipocyte-specific genes. In addition, KDMs have functions in addition to their enzymatic activity, which are beginning to be revealed, and their dysregulation seems to be related to the development of metabolic disorders. In this review, we highlight the biological functions of KDMs that contribute to the establishment of a permissive or repressive chromatin environment during the mesenchymal stem cell transition into adipocytes. Understanding how KDMs regulate adipogenesis might prompt the development of new strategies for fighting obesity-related diseases.
The impact of two doses of coenzyme Q10 on semen parameters and antioxidant status in men with idiopathic oligoasthenoteratozoospermia

Objective Oxidative stress contributes to male infertility, and antioxidants have been recommended for treating idiopathic oligoasthenoteratozoospermia (OAT). There is, however, a lack of agreement on the type, dosing, and use of individual antioxidants or combinations thereof. The purpose of this study was to compare the effects of two doses of coenzyme Q10 (CoQ10) on semen parameters and antioxidant status in men with idiopathic OAT. Methods In this prospective study, patients with idiopathic OAT received 200 mg/day (n = 35) or 400 mg/day (n = 30) of CoQ10 orally for 3 months. All patients underwent semen analysis according to the fifth editions of the World Health Organization criteria. Total antioxidant capacity (TAC), catalase (CAT) activity, and superoxide dismutase (SOD) activity were measured both before and after treatment. Results Treatment with CoQ10 (200 mg/day or 400 mg/day) resulted in a significant increase in sperm concentration from baseline (8.22 ± 6.88 to 12.53 ± 8.11 million/mL, p= 0.019; 7.58 ± 5.41 to 12.33 ± 6.1 million/mL, p= 0.002, respectively), progressive motility (16.54% ±9.26% to 22.58% ±10.15%, p=0.011; 14.22% ±12.85% to 26.1% ±14.52%, p= 0.001, respectively), and total motility (25.68% ± 6.41% to 29.96% ± 8.09%, p= 0.016; 23.46% ± 12.59% to 34.82% ± 14.17%, p= 0.001, respectively). CoQ10 therapy also increased TAC (p= 0.009, p= 0.001, respectively), SOD activity (p= 0.004, p= 0.001, respectively), and CAT activity (p= 0.039, p= 0.024, respectively). Furthermore, antioxidant measures correlated significantly with seminal fluid parameters (r = 0.36–0.76). Conclusion CoQ10 supplementation improved semen parameters and antioxidant status in men with idiopathic OAT, with a greater improvement shown in men who took 400 mg/day than in those who took 200 mg/day.
IgE Ratio in Tears: A Predictive Tool of Ocular Allergic Inflammation

ABSTRACT Purpose To demonstrate the tear IgE (measured/exuded) ratio (R) as a useful biological marker of ocular allergy in order to distinguish severe from less severe inflammatory status. Methods Tear samples and sera from 78 ocular allergy patients and 19 control subjects were analyzed. Total IgE and albumin were measured for calculating the tear IgE-R defining two subgroups (SG) of samples: R ≥ 4-SG and R < 4-SG. Eosinophil cationic protein, Th1 and Th2 cytokines (IFN-γ, IL-4, −5, −6, −8 and −10) and protein electrophoretic profiles were also investigated in tears. Results The R < 4-SG compared to the R ≥ 4-SG shows higher levels of tear albumin, eosinophil cationic protein, and Th1 and Th2 cytokines. Moreover, each subgroup presents a specific protein profile. Conclusion This study showed that an IgE-R lower than four must be carefully interpreted as a warning sign of a severe inflammatory context and should be also associated with an exploration of immunological profile.
Analysis of transmittance and degree of conversion of composite resins

The objective of this study was to evaluate and correlate light transmittance (T), initial degree of conversion (IDC), and degree of conversion after 24 hr (DC24) for 22 composite resins (CR) for enamel and dentin use. The transmittance (n = 10) was measured with a spectrometer at a wavelength of 468.14 nm. The degree of conversion (DC; n = 5) was measured with Fourier Transform Near‐Infrared Spectroscopy before polymerization, immediately after photoactivation, and 24 hr after photoactivation. Both sets of values are provided as percentages. ANOVA and Games‐Howell (α = 5%) tests showed that Filtek Supreme Ultra gave the highest T values of all enamel CRs, while Esthet‐X HD presented the lowest. Meanwhile, Venus diamond gave the highest values of all dentin CRs, while Esthet‐X HD gave the lowest. For IDC and DC24, ANOVA showed differences between individual CRs and the two CR types (p < .0001). Despite the limitations of this study, it can be concluded that there was no correlation between T and either IDC or DC24 (p > .05); however, IDC and DC24 were strongly correlated (p < .05) by Pearson's correlation. That being said, as a higher DC reflects better mechanical properties, certain conclusions can be drawn about overall performance. The best IDC values were observed for the Opallis enamel resin and the Opallis and Premise dentin resins. Meanwhile, the best DC24 values were observed for the Opallis, Charisma, and Premise enamel resins and the Opallis and Premise dentin resins.
Kinesin-8B controls basal body function and flagellum formation and is key to malaria transmission

This comprehensive study describes the key role and real-time dynamics of Plasmodium kinesin-8B in microtubule-based basal body and axoneme assembly during flagellum (male gamete) formation and parasite transmission. Eukaryotic flagella are conserved microtubule-based organelles that drive cell motility. Plasmodium, the causative agent of malaria, has a single flagellate stage: the male gamete in the mosquito. Three rounds of endomitotic division in male gametocyte together with an unusual mode of flagellum assembly rapidly produce eight motile gametes. These processes are tightly coordinated, but their regulation is poorly understood. To understand this important developmental stage, we studied the function and location of the microtubule-based motor kinesin-8B, using gene-targeting, electron microscopy, and live cell imaging. Deletion of the kinesin-8B gene showed no effect on mitosis but disrupted 9+2 axoneme assembly and flagellum formation during male gamete development and also completely ablated parasite transmission. Live cell imaging showed that kinesin-8B–GFP did not co-localise with kinetochores in the nucleus but instead revealed a dynamic, cytoplasmic localisation with the basal bodies and the assembling axoneme during flagellum formation. We, thus, uncovered an unexpected role for kinesin-8B in parasite flagellum formation that is vital for the parasite life cycle.
Response by Jordan et al to Letter Regarding Article, "Left Atrial Volume Index Is Associated With Cardioembolic Stroke and Atrial Fibrillation Detection After Embolic Stroke of Undetermined Source".

In Response: We thank Müller et al for their letter in response to our article Left Atrial Volume Index Is Associated With Cardioembolic Stroke and Atrial Fibrillation Detection After Embolic Stroke of Undetermined Source. The authors make several important observations and highlight timely ongoing discussions within the literature. Müller et al raise several questions regarding the rate of atrial fibrillation (AF) detection in the Embolic Stroke of Undetermined Subtype (ESUS) subgroup of our study population as well as our clinical definition of AF. Within the ESUS subgroup, 99/412 (24.0%) completed outpatient cardiac event monitoring with a 4-week cardiac monitor. Of those patients, AF was detected in 18 (18.2%). We agree that the loss of long-term follow-up is a major limitation in our study, and this was acknowledged in our article. In our study, we used a detection threshold for AF of >30 seconds, which was similarly used in the CRYSTAL AF study (Cryptogenic Stroke and Underlying Atrial Fibrillation) in patients with cryptogenic stroke. Comparison of AF detection rates between our study and others is not useful given differences in study populations and methods used for the detection of AF. While subclinical AF has been shown to be associated with stroke risk, the threshold duration of subclinical AF that incurs a clinically significant increased risk of ischemic stroke and benefit from anticoagulation remains uncertain and under investigation. No studies, however, presently discuss the role of subclinical AF detected after ESUS and whether ESUS is a group of patients where 30 seconds of AF confers an elevated stroke recurrence risk and benefit from anticoagulation. Although AF burden is a factor in determining stroke risk, ischemic stroke has proven to be a more important determinant of stroke risk in patients with AF. In fact, a recent meta-analysis showed reduced risk of recurrent stroke in patients with ESUS undergoing cardiac monitoring versus controls and most of the studies in this meta-analysis used the same definition used in our study. This brings us to another important distinction. Recent studies have shown no temporal association between subclinical AF and ischemic stroke, arguing that atrial dysfunction or cardiopathy and not AF is the direct cause of stroke in most patients with subclinical AF. In fact, several studies have shown associations between left atrial enlargement and ischemic stroke and with brain infarcts, particularly those related to embolism. The ARCADIA trial (Antithrombotic Drugs in Prevention After Cryptogenic Stroke; URL: https://www.clinicaltrials.gov. Unique identifier: NCT03192215) is currently investigating the role of anticoagulation in patients with ESUS and severe left atrial enlargement and we agree with Müller et al that the role of left atrial enlargement in the pathogenesis of cardioembolic stroke needs further investigation.
Evaluation of an intervention targeting loneliness and isolation for older people in North Wales

Aims: Age Cymru Gwynedd and Môn provided a service, Cadwyn Môn, which aimed to reduce loneliness and isolation of older people living on Anglesey, North Wales. It involved working with individuals to identify goals, beginning on a one-to-one basis, with the aim of integrating into a wider social setting. The aim of this study was evaluate the impact of Cadwyn Môn on those who received the service. Methods: The evaluation adopted a mixed-methods design. Standardized measures of loneliness, social isolation and well-being were obtained at baseline and follow-up time points, and a qualitative element explored client experiences further. Results: Improvements were observed in all standardized measures. Qualitative interviews also revealed important psychological and lifestyle changes. Conclusions: Given the anticipated rise in loneliness and social isolation alongside an ageing population, this evaluation contributes to understanding the qualities required for interventions to be effective. The findings provide support for the importance of developing individualized interventions that aim to gradually re-integrate people into their communities.
Getting by with a Little Help from Our Friends: The Role of Social Support in Addressing HIV-related Mental Health Disparities among Sexual Minorities in the Lower Rio Grande Valley

ABSTRACT This study examines how social support and perceived discrimination influence depressive symptoms of sexual minorities (including, lesbian, gay, bisexual-identifying individuals, and others with same-sex sexual partners) relative to heterosexual peers, while considering the role of HIV-positive status. We surveyed low-income, predominantly Hispanic/Latino/as residents receiving STI-testing and/or HIV/AIDS care in the lower Rio Grande Valley of southernmost Texas. Respondents aged 18+ took a self-administered survey in English or Spanish in a clinic waiting room (N= 273). Based on OLS regression, HIV-positive status (OLS coefficient = 2.54, p< .01) and social support (OLS coefficient = −0.17, p< .001) were significant predictors of depressive symptoms among sexual minorities, but not those who identified as heterosexual. Perceived discrimination was uniquely associated with increased depressive symptoms among sexual minorities (interaction coefficient = 0.21, p< .05). Clinicians treating sexual minority patients for depression should consider developing and applying resources tailored to individuals’ level of social support and ongoing experiences of social discrimination.
Generic properties of homogeneous Ricci solitons

Abstract We discuss the geometry of homogeneous Ricci solitons. After showing the nonexistence of compact homogeneous and non-compact steady homogeneous solitons, we concentrate on the study of left invariant Ricci solitons. We show that, in the unimodular case, the Ricci soliton equation does not admit solutions in the set of left invariant vector fields. We prove that a left invariant soliton of gradient type must be a Riemannian product with non-trivial Euclidean de Rham factor. As an application of our results we prove that any generalized metric Heisenberg Lie group is a non-gradient left invariant Ricci soliton of expanding type.
Surfactant Protein-D Modulation of Pulmonary Macrophage Phenotype is Controlled by S-Nitrosylation.

Surfactant protein-D (SP-D), a regulator of pulmonary innate immunity, whose oligomeric state can be altered through S-nitrosylation to regulate its signaling function in macrophages. Here, we examined how nitrosylation of SP-D alters the phenotypic response of macrophages to stimuli, both in vivo and in vitro. Bronchoalveolar lavage (BAL) from C57/Bl6 and SP-D overexpressing (SP-D OE) mice was incubated with RAW264.7 cells ± LPS. LPS induces expression of inflammatory genes, IL1B and NOS2, which is reduced 10-fold by SP-D OE-BAL. S-nitrosylation of the SP-D OE-BAL (SNO-SP-D OE-BAL) abrogated this inhibition. SNO-SP-D OE-BAL alone induced IL1B and NOS2 expression. PCR array analysis of macrophages incubated with SP-D OE-BAL (± LPS) shows increased expression of repair genes, CCL20, CXCL1, and VCAM1, which was accentuated by LPS. LPS increases inflammatory gene expression, IL1A, NOS2, TNF and PTGS2, that was accentuated by SNO-SP-D OE-BAL but inhibited by SP-D OE-BAL. The transcription factor NF-kB was identified as a target for SNO-SP-D by IPA, which was confirmed by Trans-AM ELISA in vitro. In vivo, SP-D overexpression increases the burden of infection in a Pneumocystis model while increasing cellular recruitment. Expression of iNOS and the production of NO metabolites are significantly reduced in SP-D OE mice relative to C57Bl6/J. Inflammatory gene expression was increased in infected C57Bl6 mice but decreased in SP-D OE. SP-D oligomeric structure was disrupted in C57Bl6 infected mice but unaltered within SP-D OE. Thus SP-D modulates macrophage phenotype and that the balance of multimeric to trimeric SP-D is critical to this regulation.
Pannexin‐1 promotes NLRP3 activation during apoptosis but is dispensable for canonical or noncanonical inflammasome activation

Inflammasomes are multimeric protein complex that assemble in the cytosol upon microbial infection or cellular stress. Upon activation, inflammasomes drive the maturation of proinflammatory cytokines, IL‐1β and IL‐18, and also activate the pore‐forming protein, gasdermin D to initiate a form of lytic cell death known as “pyroptosis”. Pannexin‐1 is channel‐forming glycoprotein that promotes membrane permeability and ATP release during apoptosis; and was implicated in canonical NLRP3 or noncanonical inflammasome activation. Here, by utilizing three different pannexin‐1 channel inhibitors and two lines of Panx1–/– macrophages, we provide genetic and pharmacological evidence that pannexin‐1 is dispensable for canonical or noncanonical inflammasome activation. In contrast, we demonstrate that pannexin‐1 cleavage and resulting channel activity during apoptosis promotes NLRP3 inflammasome activation.
Molecular Characterization and Moxifloxacin Susceptibility of Clostridium difficile

In recent years, the incidence and severity of Clostridium difficile infections has increased. Additionally, resistance of C. difficile to frequently used antibiotics is rising. To improve our understanding of C. difficile, there is a need for molecular characterization of different strains and antibiotic resistance testing. We investigated the efficacy of GenoType CDiff kit (Hain Lifesciences) in identification of C. difficile and its various strains in northern Israel. The kit involves a molecular assay that detects C. difficile from stool samples or colonies and identifies the different strains and mutations in the gyrA gene that cause moxifloxacin resistance. Forty-nine C. difficile positive samples were examined by the kit following DNA extraction from both colonies and stool. The identification rate (95.9%) of C. difficile was much higher when DNA was extracted from colonies, compared to extraction from stool (46.9%). Low frequencies of ribotype027 strain (2%) and of ribotype078 strain (4%) were found. There was a high concordance between genotype (mutation in gyrA) and phenotype (Etest) for moxifloxacin resistance (Kappa = 0.72). A high percentage of moxifloxacin-resistant strains was found. Our findings indicate that the GenoType CDiff kit is very effective in characterization of C. difficile strains and less effective for identification of C. difficile directly from stool samples.
Immunohistochemical expression of CD44v9 and 8‐OHdG in ovarian endometrioma and the benign endometriotic lesions adjacent to clear cell carcinoma

Expression of CD44 variant isoforms (CD44v) promotes the synthesis of reduced glutathione and contributes to reactive oxygen species defense through up‐regulation of the intracellular antioxidant. The aim of the study was to investigate the expression of CD44v9 and oxidative DNA damage marker, 8‐OHdG, in benign ovarian endometrioma (OE) and OE harboring clear cell carcinomas (CCC).