Miracle-dz/UniFAR-FTUs huggingface dataset:
Illuminating Neural Circuits: From Molecules to MRI

Neurological disease drives symptoms through pathological changes to circuit functions. Therefore, understanding circuit mechanisms that drive behavioral dysfunction is of critical importance for quantitative diagnosis and systematic treatment of neurological disease. Here, we describe key technologies that enable measurement and manipulation of neural activity and neural circuits. Applying these approaches led to the discovery of circuit mechanisms underlying pathological motor behavior, arousal regulation, and protein accumulation. Finally, we discuss how optogenetic functional magnetic resonance imaging reveals global scale circuit mechanisms, and how circuit manipulations could lead to new treatments of neurological diseases.
G9a coordinates with the RPA complex to promote DNA damage repair and cell survival

Significance The G9a histone methyltransferase primarily regulates the expression of genes associated with cancer development in cancer cells, but it has also been implicated in mediating the DNA damage response. Here, we confirmed a role for G9a in DNA damage repair following double-strand breaks. G9a is recruited to chromatin as a result of casein kinase 2-mediated phosphorylation, where it directly interacts with replication protein A (RPA). G9a binding to RPA modulates RPA and Rad51 foci formation and permits efficient homologous recombination. This molecular mechanism renders cancer cells more resistant to radiation and chemotherapeutics. Our improved understanding of the molecular function of G9a may help with the future design of G9a inhibitors and G9a-based DNA damage agents as cancer therapeutics. Histone methyltransferase G9a has critical roles in promoting cancer-cell growth and gene suppression, but whether it is also associated with the DNA damage response is rarely studied. Here, we report that loss of G9a impairs DNA damage repair and enhances the sensitivity of cancer cells to radiation and chemotherapeutics. In response to DNA double-strand breaks (DSBs), G9a is phosphorylated at serine 211 by casein kinase 2 (CK2) and recruited to chromatin. The chromatin-enriched G9a can then directly interact with replication protein A (RPA) and promote loading of the RPA and Rad51 recombinase to DSBs. This mechanism facilitates homologous recombination (HR) and cell survival. We confirmed the interaction between RPA and G9a to be critical for RPA foci formation and HR upon DNA damage. Collectively, our findings demonstrate a regulatory pathway based on CK2–G9a–RPA that permits HR in cancer cells and provide further rationale for the use of G9a inhibitors as a cancer therapeutic.
Using Resin‐Based 3D Printing to Build Geometrically Accurate Proxies of Porous Sedimentary Rocks

Three‐dimensional (3D) printing is capable of transforming intricate digital models into tangible objects, allowing geoscientists to replicate the geometry of 3D pore networks of sedimentary rocks. We provide a refined method for building scalable pore‐network models (“proxies”) using stereolithography 3D printing that can be used in repeated flow experiments (e.g., core flooding, permeametry, porosimetry). Typically, this workflow involves two steps, model design and 3D printing. In this study, we explore how the addition of post‐processing and validation can reduce uncertainty in the 3D‐printed proxy accuracy (difference of proxy geometry from the digital model). Post‐processing is a multi‐step cleaning of porous proxies involving pressurized ethanol flushing and oven drying. Proxies are validated by: (1) helium porosimetry and (2) digital measurements of porosity from thin‐section images of 3D‐printed proxies. 3D printer resolution was determined by measuring the smallest open channel in 3D‐printed “gap test” wafers. This resolution (400 µm) was insufficient to build porosity of Fontainebleau sandstone (∼13%) from computed tomography data at the sample's natural scale, so proxies were printed at 15‐, 23‐, and 30‐fold magnifications to validate the workflow. Helium porosities of the 3D‐printed proxies differed from digital calculations by up to 7% points. Results improved after pressurized flushing with ethanol (e.g., porosity difference reduced to ∼1% point), though uncertainties remain regarding the nature of sub‐micron “artifact” pores imparted by the 3D printing process. This study shows the benefits of including post‐processing and validation in any workflow to produce porous rock proxies.
A combined high-sugar and high-saturated-fat dietary pattern is associated with more depressive symptoms in a multi-ethnic population: the HELIUS (Healthy Life in an Urban Setting) study

Abstract Objective To identify a high-sugar (HS) dietary pattern, a high-saturated-fat (HF) dietary pattern and a combined high-sugar and high-saturated-fat (HSHF) dietary pattern and to explore if these dietary patterns are associated with depressive symptoms. Design We used data from the HELIUS (Healthy Life in an Urban Setting) study and included 4969 individuals aged 18–70 years. Diet was assessed using four ethnic-specific FFQ. Dietary patterns were derived using reduced rank regression with mono- and disaccharides, saturated fat and total fat as response variables. The nine-item Patient Health Questionnaire (PHQ-9) was used to assess depressive symptoms by using continuous scores and depressed mood (identified using the cut-off point: PHQ-9 sum score ≥10). Setting The Netherlands. Results Three dietary patterns were identified; an HSHF dietary pattern (including chocolates, red meat, added sugars, high-fat dairy products, fried foods, creamy sauces), an HS dietary pattern (including sugar-sweetened beverages, added sugars, fruit (juices)) and an HF dietary pattern (including high-fat dairy products, butter). When comparing extreme quartiles, consumption of an HSHF dietary pattern was associated with more depressive symptoms (Q1 v. Q4: β=0·18, 95 % CI 0·07, 0·30, P=0·001) and with higher odds of depressed mood (Q1 v. Q4: OR=2·36, 95 % CI 1·19, 4·66, P=0·014). No associations were found between consumption of the remaining dietary patterns and depressive symptoms. Conclusions Higher consumption of an HSHF dietary pattern is associated with more depressive symptoms and with depressed mood. Our findings reinforce the idea that the focus should be on dietary patterns that are high in both sugar and saturated fat.
Mid-Season Estimates of Influenza Vaccine Effectiveness against Influenza A(H3N2) Hospitalization in the Elderly in Quebec, Canada, January 2015

Background The 2014/15 influenza season in Canada was characterized by an early epidemic due to vaccine-mismatched influenza A(H3N2) viruses, disproportionately affecting elderly individuals ≥65-years-old. We assessed vaccine effectiveness (VE) against A(H3N2) hospitalization among elderly individuals during the peak weeks of the 2014/15 epidemic in Quebec, Canada. Methods Nasal specimens and clinical/epidemiological data were collected within 7 days of illness onset from elderly patients admitted with respiratory symptoms to one of four participating hospitals between November 30, 2014 and January 13, 2015. Cases tested RT-PCR positive for influenza A(H3N2) and controls tested negative for any influenza. VE was assessed by test-negative case-control design. Results There were 314 participants including 186 cases (62% vaccinated) and 128 controls (59% vaccinated) included in primary VE analysis. Median age was 81.5 years, two-thirds were admitted from the community and 91% had underlying comorbidity. Crude VE against A(H3N2) hospitalization was -17% (95%CI: -86% to 26%), decreasing to -23% (95%CI: -99 to 23%) with adjustment for age and comorbidity, and to -39% (95%CI: -142 to 20%) with additional adjustment for specimen collection interval, calendar time, type of residence and hospital. In sensitivity analyses, VE estimates were improved toward the null with restriction to participants admitted from the community (-2%; 95%CI: -105 to 49%) or with specimen collection ≤4 days since illness onset (- 8%; 95%CI: -104 to 43%) but further from the null with restriction to participants with comorbidity (-51%; 95%CI: -169 to 15%). Conclusion The 2014/15 mismatched influenza vaccine provided elderly patients with no cross-protection against hospitalization with the A(H3N2) epidemic strain, reinforcing the need for adjunct protective measures among high-risk individuals and improved vaccine options.
Scent of a Dragonfly: Sex Recognition in a Polymorphic Coenagrionid

In polymorphic damselflies discrimination of females from males is complex owing to the presence of androchrome and gynochrome females. To date there is no evidence that damselflies use sensory modalities other than vision (and tactile stimuli) in mate searching and sex recognition. The results of the present behavioural and electrophysiological investigations on Ischnura elegans, a polymorphic damselfly, support our hypothesis that chemical cues could be involved in Odonata sex recognition. The bioassays demonstrate that males in laboratory prefer female to male odour, while no significant difference was present in male behavior between stimuli from males and control. The bioassays suggest also some ability of males to distinguish between the two female morphs using chemical stimuli. The ability of male antennae to perceive odours from females has been confirmed by electrophysiological recordings. These findings are important not only to get insight into the chemical ecology of Odonata, and to shed light into the problem of olfaction in Paleoptera, but could be useful to clarify the controversial aspects of the mating behavior of polymorphic coenagrionids. Behavioural studies in the field are necessary to investigate further these aspects.
Early Versus Delayed Initiation of Pharmacological Venous Thromboembolism Prophylaxis After an Intracranial Hemorrhage

Background: Intracranial hemorrhage (ICH) accounts for up to 20% of all strokes with and carries an approximate 50% 30-day mortality. The risk of venous thromboembolism (VTE) is markedly higher in patients with ICH compared with ischemic strokes, but the optimal time to initiate pharmacological prophylaxis is ill-defined. Design: Retrospective analysis. Setting: University-affiliated, tertiary care center. Patients: Patients admitted for a nontraumatic ICH who received pharmacological VTE prophylaxis during their first 30 hospital days. Results: Of the 793 patients evaluated, 400 were included [142 (35.5%) early]. Rebleeding event rates were similar for early versus late [8 (5.6%) vs. 13 (5.0%), P=0.80] and rates of hospital-acquired VTEs were not statistically different [1 (0.7%) vs. 8 (3.1%), P=0.17]. The median time from admission to the first dose of pharmacological prophylaxis was similar in patients who experienced rebleeding versus those that did not [74 h (range, 38 to 110.5 h) vs. 63 h (range, 45 to 90.5 h), P=0.69]. There was a longer median time from admission to the first dose of pharmacological prophylaxis in patients who developed a VTE during the initial hospitalization versus those who did not [108 h (range, 73.3 to 187 h) vs. 63 h (range, 44.5 to 90 h), P=0.005]. Conclusions: Initiation of early pharmacological prophylaxis in ICH patients did not appear to increase the risk of rebleeding nor decrease the risk of VTE. Among those patients who did develop VTE during hospitalization, there was a longer median time from admission to the first dose of pharmacological prophylaxis.
Mortality prediction using serum biomarkers and various clinical risk scales in community-acquired pneumonia

Abstract We evaluated the predictive value of serum biomarkers and various clinical risk scales for the 28-day mortality of community-acquired pneumonia (CAP). Serum biomarkers including procalcitonin (PCT) and C-reactive protein (CRP) were evaluated in the emergency department. Scores for the pneumonia severity index (PSI); CURB65 (confusion, urea, respiration, blood pressure; age >65 years); Infectious Disease Society of America (IDSA) and American Thoracic Society (ATS) guidelines for severe CAP; Acute Physiology, Chronic Health Evaluation (APACHE) II; Sequential Organ Failure Assessment (SOFA); and quick SOFA (qSOFA) were calculated. Receiver-operating characteristic curves for 28-day mortality were calculated for each predictor using cut-off values, and we applied logistic regression models and area under the curve (AUC) analysis to compare the performance of predictors. Of the 125 enrolled patients, 13 died within 28 days. The AUCs of the PCT and CRP were 0.83 and 0.77, respectively. Using a PCT level >5.6 μg/L as the cut-off, the sensitivity and specificity for mortality were 76.9% and 90.2%, respectively. The three pneumonia severity scales showed an AUC of 0.86 (PSI), 0.87 (IDSA/ATS) and 0.77 (CURB65). The AUCs of the APACHE II, SOFA and qSOFA scores were 0.85, 0.83 and 0.81, respectively. The models combining CRP and/or PCT with PSI or the IDSA/ATS guidelines demonstrated superior performance to those of either PSI or the IDAS/ATS guidelines alone. In conclusion, serum PCT is a reliable single predictor for short-term mortality. Inclusion of CRP and/or PCT could significantly improve the performance of the PSI and IDAS/ATS guidelines.
Kinesin superfamily protein expression and its association with progression and prognosis in hepatocellular carcinoma.

OBJECTIVES In this study, we characterized the expression of 32 other kinesin superfamily proteins (KIFs) and analyzed their association with the progression and prognosis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS The data from 295 HCC patients from The Cancer Genome Atlas were included in the study. An independent t-test was used to compare the KIF levels in HCC and adjacent tissues. Pearson's Chi-square test was used to assess the relationships of KIF expression with tumor biomarkers and clinicopathological parameters. Kaplan-Meier plots and log-rank tests were used to analyze survival, and univariate and multivariate analyses were used to identify independent prognostic factors. RESULTS The expressions of 32 KIFs were compared between HCC and adjacent nontumor tissues. Among them, 12 KIFs showed no statistical significance, 17 KIFs were upregulated, and three KIFs were downregulated in tumor tissues. The levels of some KIFs were markedly correlated with that of biomarkers for the S phase and proliferation. KIF2A and KIFC3 expression was positively associated with biomarkers for cell invasion and migration. Some KIF overexpression was significantly associated with neoplastic pathological grade and tumor-node-metastasis staging. Furthermore, KIF2C, KIF4A, and KIF11 overexpression were significantly associated with shorter relapse-free survival times. KIF2A, KIF2C, KIF3A, KIF4B, KIF11, KIF15, KIFC1, and KIFC3 overexpression was associated with shorter overall survival (OS) times, whereas higher expression of KIF19 was associated with a longer OS time. Further multivariate analyses suggested that only KIF4B was an independent prognostic factor for HCC. CONCLUSIONS Most overexpressions of abnormal KIFs were significantly associated with HCC progression and prognosis, indicating that KIFs could be prognostic and therapeutic biomarkers for HCC. However, it is necessary to further study the function of KIFs and their mechanisms involved in HCC.
Elevation of Platelet and Monocyte Activity Markers of Atherosclerosis in Haemodialysis Patients Compared to Peritoneal Dialysis Patients

Purpose The predominant cause of mortality in dialysis patients are cardiovascular events. Platelet and monocyte activity markers play an important role in cardiovascular mortality and were assessed and related to dialysis quality criteria in haemodialysis (HD) and peritoneal dialysis (PD) patients. Methods For this prospective comparative study, HD patients (n = 41) and PD patients (n = 10) were included. In whole blood samples, surface expression of CD62P and CD40L on platelets, tissue factor binding on monocytes, and platelet-monocyte aggregates were measured by flow cytometry. Plasma levels of MCP-1, IL-6, TNFα, and soluble CD40L were analysed by enzyme-linked immunosorbent assay. Results Haemodialysis patients showed a significantly higher CD62P expression on platelets (p = 0.017), significantly higher amount of platelet-monocyte aggregates (p < 0.0001), and significantly more tissue factor binding on monocytes (p < 0.0001) compared to PD patients. In PD patients, a significant correlation between Kt/V and platelet CD40L expression (r = 0.867; 0.001) and between Kt/V and platelet CD62P expression (r = 0.686; p = 0.028) was observed, while there was no significant correlation between Kt/V and tissue factor binding on monocytes and platelet-monocyte aggregates, respectively. Conclusion Platelet and monocyte activity markers are higher in HD patients in comparison with those in PD patients, possibly suggesting a higher risk of cardiovascular morbidity and mortality.
Dietary soy and tea combinations for prevention of breast and prostate cancers by targeting metabolic syndrome elements in mice.

BACKGROUND The prevalence of metabolic syndrome is high and is increasing in parallel with increasing incidences of breast and prostate cancers. The combination of soy with tea was shown to have synergistic effects on preventing breast and prostate tumors, but the effects of soy and tea combinations on metabolic syndrome-related elements have not been investigated. OBJECTIVE We aimed to determine the effects of soy and tea components, alone and in combination, on abdominal adipose mass and serum concentrations of adipokines, growth factors, and sex hormones in male and female mice. DESIGN Male and female FVB/N mice were treated with soy, tea components, or both. Food intake and body weight were monitored weekly. At the end of the experiment, abdominal white adipose tissue was weighed, and serum concentrations of biomarkers were measured. RESULTS Whole teas, but not the tea polyphenol extracts, significantly reduced abdominal white adipose tissue by 43-60% in female mice and by 65-70% in male mice. The combination of soy phytochemical concentrate and green tea reduced serum insulin-like growth factor-I concentrations in both male and female mice in a synergistic manner. The soy phytochemical concentrate and tea combinations reduced serum estrogen concentrations in female mice in a synergistic manner. Soy phytochemical concentrate and teas also significantly reduced serum leptin concentrations in both male and female mice and testosterone concentrations in male mice. CONCLUSION Further research is warranted to investigate whether soy and tea combinations may prevent breast or prostate cancer in a synergistic manner in part by alleviating metabolic disorders.
Computer-aided design of carbon nanotubes with the desired bioactivity and safety profiles

Abstract Growing experimental evidences suggest the existence of direct relationships between the surface chemistry of nanomaterials and their biological effects. Herein, we have employed computational approaches to design a set of biologically active carbon nanotubes (CNTs) with controlled protein binding and cytotoxicity. Quantitative structure–activity relationship (QSAR) models were built and validated using a dataset of 83 surface-modified CNTs. A subset of a combinatorial virtual library of 240 000 ligands potentially attachable to CNTs was selected to include molecules that were within the chemical similarity threshold with respect to the modeling set compounds. QSAR models were then employed to virtually screen this subset and prioritize CNTs for chemical synthesis and biological evaluation. Ten putatively active and 10 putatively inactive CNTs decorated with the ligands prioritized by virtual screening for either protein-binding or cytotoxicity assay were synthesized and tested. We found that all 10 putatively inactive and 7 of 10 putatively active CNTs were confirmed in the protein-binding assay, whereas all 10 putatively inactive and 6 of 10 putatively active CNTs were confirmed in the cytotoxicity assay. This proof-of-concept study shows that computational models can be employed to guide the design of surface-modified nanomaterials with the desired biological and safety profiles.
Clinical and angiographic outcome of a single center, real world population treated with a dedicated technique of implantation for bioresorbable vascular scaffolds. The FAtebenefratelli Bioresorbable Vascular Scaffold (FABS) registry

OBJECTIVES With this prospective study we aim at investigating the long-term outcome of a consecutive cohort of patients successfully treated with bioresorbable scaffold (BVS) implantation. BACKGROUND It is not clearly understood if there is a relation between the technique of BVS implantation and the outcome. METHODS Between December 2012 and December 2014, all consecutive patients treated with BVS were included in this registry and received an angiographic follow-up. After a run-in phase, all BVS were implanted using a specific technique consisting of aggressive predilation, correct scaffold sizing, visually determined, and high-pressure post-dilation with a noncompliance balloon. Primary endpoint was late lumen loss (LLL) at 1-year angiographic follow-up and ischemia-driven target-lesion revascularization (ID-TLR) at 2-year clinical follow-up. Secondary endpoints were the occurrence of binary restenosis, major adverse cardiac events (MACE), and every single component of MACE (cardiac death, myocardial infarction, TLR) at 2 years. RESULTS A total of 144 lesions in 122 patients treated consecutively with BVS, were enrolled. Diabetics were 29.5% and acute coronary syndrome at presentation occurred in 29.5% of patients. At the angiographic follow-up LLL was 0.38 ± 0.9. At 2-year clinical follow-up, ID-TLR occurred in eight patients (5.6%). We observed two cases of scaffold thrombosis (1.38%, one early and one very late). At multivariate statistical analysis, STEMI presentation remained a significant predictor for TLR. CONCLUSIONS In a complex, all-comers real world population, BVS implantation with a specific, and standardized technique showed to be feasible, with acceptable mid-term angiographic and long-term clinical outcome.
Deep D-Bar: Real-Time Electrical Impedance Tomography Imaging With Deep Neural Networks

The mathematical problem for electrical impedance tomography (EIT) is a highly nonlinear ill-posed inverse problem requiring carefully designed reconstruction procedures to ensure reliable image generation. D-bar methods are based on a rigorous mathematical analysis and provide robust direct reconstructions by using a low-pass filtering of the associated nonlinear Fourier data. Similarly to low-pass filtering of linear Fourier data, only using low frequencies in the image recovery process results in blurred images lacking sharp features, such as clear organ boundaries. Convolutional neural networks provide a powerful framework for post-processing such convolved direct reconstructions. In this paper, we demonstrate that these CNN techniques lead to sharp and reliable reconstructions even for the highly nonlinear inverse problem of EIT. The network is trained on data sets of simulated examples and then applied to experimental data without the need to perform an additional transfer training. Results for absolute EIT images are presented using experimental EIT data from the ACT4 and KIT4 EIT systems.