Miracle-dz/UniFAR-FTUs huggingface dataset:
Leishmania infantum, Dirofilaria spp. and other endoparasite infections in kennel dogs in central Italy

Prevalence and risk factors of Leishmania infantum, Dirofilaria spp. and other potentially zoonotic or canine-specific endoparasite infections were assessed in 639 kennel dogs from central Italy. To this end, individual blood and fecal samples were examined using parasitological, immunological and molecular techniques. The presence of compatible clinical pictures, as well as age and gender were considered as putative risks factors. To evaluate risk factors, multivariable analysis with logistic regression and univariable analysis with a Chi square test and a Fischer’s exact test were performed. Overall, 52.6% of dogs (95% CI 48.6-56.5) were found positive, while 39.6% of dogs (95% CI 35.8-43.5) were infected by potentially zoonotic species. Leishmania infantum and Dirofilaria repens showed prevalences of 2.5% (95% CI 1.5-4.1) and 2.8% (95% CI 1.7-4.5), respectively. The prevalence of cardiorespiratory parasites was 7.8% (95% CI 5.9-10.3) and included the species Angiostrongylus vasorum, Eucoleus aerophilus, Eucoleus boehmi and D. immitis; the latter showed a prevalence of 0.2% (95% CI 0.001-1). Intestinal parasites were significantly prevalent (38.8%, 95% CI 35-42.7) and they consisted mainly of species of major zoonotic concern, including ancylostomatids, Toxocara canis, Giardia duodenalis, Dipylidium caninum, Taeniidae, Strongyloides stercoralis and Cryptosporidium parvum. Endoparasites were significantly prevalent in clinically suspected dogs. Leishmania infantum and cardiorespiratory nematodes were prevalent in older dogs, while intestinal parasites were prevalent in younger dogs. Results show high dog and public health risks in kennels in central Italy, and suggest the need for more effective control measures.
Venlafaxine and sertraline does not affect the expression of genes regulating stress response in female MDD patients.

OBJECTIVES The aim of this study was to analyze the expression of 3 genes involved in the regulation of HPA axis: GR, HSP90 and FKBP5, in patients with major depressive disorder (MDD) before antidepressant treatment and after 8 weeks of pharmacotherapy. Additionally, we analyzed the level of glucocorticoid receptor isoforms before and after treatment. METHODS The study included 30 female patients (aged 18-60 years), with major depres- sive disorder diagnosed on the basis of the Structured Clinical Interview for DSM-IV (SCID). Antidepressant treatment included use of sertraline or venlafaxine. The assessment of patients' mental state (severity of depression) was checked by the Hamilton Depression Rating Scale (HDRS). After 8 weeks of treatment, the same clinical and molecular tests were performed. All of the patients underwent dexamethasone suppression test (DST). MRNA was isolated from the peripheral blood to evaluate the expression of the studied genes using real-time PCR with TaqMan probes. The concentration of GR isoforms (α and β) in serum was also determined using ELISA. Statistical analysis was performed using Statistica v.12. 0 software. RESULTS The abnormal cortisol level was only seen in 20% of patients. Dysregulation on HPA axis was observed in 10% of patients. We observed significant clinical improvement after 8 weeks of pharmacotherapy in all patients. Almost the whole group of patients (except one patient) showed full remission of symptoms. We observed significant moderate correlation between cortisol level after DST before treatment and after 8 weeks of pharmacotherapy (r2 = 0.44). The results showed no significant difference in the expression of 3 analyzed genes compared before and after 8 weeks of therapy. The results of ELISA showed decreased level of α isoform after pharmacotherapy, independent of drug. CONCLUSIONS The results showed no significant changes in the expression of genes involved in the stress axis activity during antidepressant therapy.
How effective is nonlaxative treatment of constipation?

In almost any textbook of medicine so-called simple measures are proposed for treating constipation, such as increasing physical activity, drinking more fluid, triggering the gastrocolonic response by, e.g., drinking a glass of water or a cup of coffee, and bowel training. All of these have not been formally evaluated in constipated patients. Biofeedback training is useful for paradoxical puborectal contraction ('anismus'). Dietary fibre, e.g. in the form of wheat bran, increases stool weight and decreases colonic transit time. So every patient should have an empiric treatment with an adequate amount of fibre. Some patients, especially those with slow transit constipation and those with stasis in the right hemicolon, are not likely to respond to a therapy with bran, however.
Association Between Circulating Tumor DNA and Pseudoprogression in Patients With Metastatic Melanoma Treated With Anti–Programmed Cell Death 1 Antibodies

Importance Longitudinal circulating tumor DNA (ctDNA) has been shown to predict response and survival in patients with metastatic melanoma treated with anti–programmed cell death 1 (PD-1) antibodies. Pseudoprogression, defined as radiologic finding of disease progression prior to response, has been a challenge to clinicians. Objective To establish whether ctDNA at baseline and up to week 12 of treatment can differentiate between the radiologic findings of pseudoprogression and true progression in patients with metastatic melanoma. Design, Setting, and Participants This explorative biomarker study examined circulating BRAF and NRAS mutations in a cohort of 125 patients with melanoma receiving PD-1 antibodies alone or in combination with ipilimumab between July 3, 2014, and May 24, 2016. Pseudoprogression was defined retrospectively as radiologic progression not confirmed as progressive disease at the next radiologic assessment. Plasma samples of ctDNA at baseline and while receiving treatment were taken for analysis prospectively over the first 12 weeks of treatment. Favorable ctDNA profile (undetectable ctDNA at baseline or detectable ctDNA at baseline followed by >10-fold decrease) and unfavorable ctDNA profile (detectable ctDNA at baseline that remained stable or increased) were correlated with response and prognosis. Main Outcomes and Measures Early differentiation of pseudoprogression from true progression using longitudinal ctDNA profile. Results According to guidelines by Response Evaluation Criteria in Solid Tumors (RECIST), progressive disease occurred in 29 of the 125 patients (23.2%). Of the 29 patients, 17 (59%) were 65 years or younger, 18 (62%) were men, 9 (31%) had pseudoprogression, and 20 (69%) had true progression. Of the 9 patients (7%) with confirmed pseudoprogression, all patients had a favorable ctDNA profile. At a median follow-up of 110 weeks, 7 of 9 patients (78%) were alive. All but 2 patients with true progression had an unfavorable ctDNA profile. Sensitivity of ctDNA for predicting pseudoprogression was 90% (95% CI, 68%-99%) and specificity was 100% (95% CI, 60%-100%). The 1-year survival for patients with RECIST-defined progressive disease and favorable ctDNA was 82% vs 39% for unfavorable ctDNA (hazard ratio [HR], 4.8; 95% CI, 1.6-14.3; P = .02). Overall survival was longer in patients with a partial response (54 of 125 patients [43%]) compared with patients with progressive disease and a favorable ctDNA profile (11 of 125 patients [9%]; HR, 0.09; 95% CI, 0.01-0.80; P < .01). Conclusions and Relevance The results demonstrate that ctDNA profiles can accurately differentiate pseudoprogression from true progression of disease in patients with melanoma treated with PD-1 antibodies. Results of this blood test performed at regular intervals during systemic treatment reflect tumor biology and have potential as a powerful biomarker to predict long-term response and survival.
Study of amino groups of the human platelet membrane.

The authors attempted to evaluate different reagents in order to quantify the amino groups of the platelet membrane. The study was carried out by the action of different aldehydes and acid anhydrides. The use of 2,4,6-trinitrobenzenesulfonic acid made possible an approach by electrophoresis and chemical assay. The results showed an increase in the surface charge corresponding to a mean number of amino groups varying from 1.86. 10(5) groups with citraconic acid to 3.94. 10(5) groups with acetaldehyde.
The connection between the breast and heart in a woman: Breast cancer and cardiovascular disease

Cardiovascular disease remains the leading cause of death in women in the United States and is a major public health issue for all women, but it is of increasing concern to breast cancer survivors. Advancements in early detection and breast cancer therapy have resulted in over 90% of women surviving 5 years past their diagnosis of breast cancer. Nonetheless, with increased survivorship from breast cancer, there has been an increase in cardiovascular disease in these women. The consequences of the treatments for breast cancer may increase the risk for cardiovascular disease. Additionally, there is an overlap of risk factors common to both breast cancer and cardiovascular disease. The increased risk of cardiovascular disease in women who survive breast cancer must be recognized, with a focus on the prevention and early detection of cardiovascular disease.
Effectiveness of Music Therapy on Focused Attention, Working Memory and Stress in Type 2 Diabetes: An Exploratory Study

Cognitive deficits are reported in diabetes mellitus type 2 (DM2). Previous research has shown that music-based intervention can not only reduce hyperglycemia but also target cognitive functions as well as stress. The aim of this exploratory study was to understand the effect of active participation in music therapy (MT) on the cognitive deficits of DM2 patients. MT of twenty sessions was carried out with three participants with DM2. Serum cortisol, perceived stress, Color Trail Test (1 and 2), and verbal n-back (1 and 2) tests were used to measure the outcomes. Feedback was taken for the subjective ratings and satisfaction of the participants. Stress and cortisol reduced and focused attention and working memory improved in varying degrees. Subjectively, participants reported having benefitted from the intervention. This is the first attempt to investigate the effect of music-based intervention on cognitive function in DM2 patients using case study approach.
A study on landmark detection based on CTC and its application to pronunciation error detection

Acoustic features extracted in the vicinity of landmarks have demonstrated their usefulness for detecting mispronunciation in our recent work [1, 2]. Traditional approaches of detecting acoustic landmarks rely on annotations by linguists with prior knowledge of speech production mechanisms, which are laborious and expensive. This paper proposes a data-driven approach of connectionist temporal classification (CTC) that can detect landmarks without any human labels while still maintaining consistent performance with knowledge-based models for stop burst landmarks. We designed an acoustic model to predict phone labels based on a recurrent neural network (RNN) with bidirectional long short- term memory (BLSTM) units, which is trained by CTC technique. We found that the positions of spiky phone outputs of this model are consistent with the landmarks annotated in the TIMIT corpus. Both data-driven and knowledge-based landmark models are applied to detect pronunciation errors of second-language (L2) Chinese learners. Experiments illustrate that data-driven CTC landmark model is comparable to knowledge-based model in pronunciation error detection. The fusion of them can further improve performance.
A Single Amino Acid Mutation Converts (R)-5-Diphosphomevalonate Decarboxylase into a Kinase*

The biosynthesis of isopentenyl diphosphate, a fundamental precursor for isoprenoids, via the mevalonate pathway is completed by diphosphomevalonate decarboxylase. This enzyme catalyzes the formation of isopentenyl diphosphate through the ATP-dependent phosphorylation of the 3-hydroxyl group of (R)-5-diphosphomevalonate followed by decarboxylation coupled with the elimination of the 3-phosphate group. In this reaction, a conserved aspartate residue has been proposed to be involved in the phosphorylation step as the general base catalyst that abstracts a proton from the 3-hydroxyl group. In this study, the catalytic mechanism of this rare type of decarboxylase is re-investigated by structural and mutagenic studies on the enzyme from a thermoacidophilic archaeon Sulfolobus solfataricus. The crystal structures of the archaeal enzyme in complex with (R)-5-diphosphomevalonate and adenosine 5′-O-(3-thio)triphosphate or with (R)-5-diphosphomevalonate and ADP are newly solved, and theoretical analysis based on the structure suggests the inability of proton abstraction by the conserved aspartate residue, Asp-281. Site-directed mutagenesis on Asp-281 creates mutants that only show diphosphomevalonate 3-kinase activity, demonstrating that the residue is required in the process of phosphate elimination/decarboxylation, rather than in the preceding phosphorylation step. These results enable discussion of the catalytic roles of the aspartate residue and provide clear proof of the involvement of a long predicted intermediate, (R)-3-phospho-5-diphosphomevalonate, in the reaction of the enzyme.
TsNAC1 Is a Key Transcription Factor in Abiotic Stress Resistance and Growth1

TsNAC1 improves abiotic stress resistance of Thelungiella halophila by regulating ion transport and retards vegetative growth by limiting the expansion of cells. NAC proteins constitute one of the largest families of plant-specific transcription factors, and a number of these proteins participate in the regulation of plant development and responses to abiotic stress. T. HALOPHILA STRESS RELATED NAC1 (TsNAC1), cloned from the halophyte Thellungiella halophila, is a NAC transcription factor gene, and its overexpression can improve abiotic stress resistance, especially in salt stress tolerance, in both T. halophila and Arabidopsis (Arabidopsis thaliana) and retard the growth of these plants. In this study, the transcriptional activation activity of TsNAC1 and RD26 from Arabidopsis was compared with the target genes’ promoter regions of TsNAC1 from T. halophila, and the results showed that the transcriptional activation activity of TsNAC1 was higher in tobacco (Nicotiana tabacum) and yeast. The target sequence of the promoter from the target genes also was identified, and TsNAC1 was shown to target the positive regulators of ion transportation, such as T. HALOPHILA H+-PPASE1, and the transcription factors MYB HYPOCOTYL ELONGATION-RELATED and HOMEOBOX12. In addition, TsNAC1 negatively regulates the expansion of cells, inhibits LIGHT-DEPENDENT SHORT HYPOCOTYLS1 and UDP-XYLOSYLTRANSFERASE2, and directly controls the expression of MULTICOPY SUPPRESSOR OF IRA14. Based on these results, we propose that TsNAC1 functions as an important upstream regulator of plant abiotic stress responses and vegetative growth.
Surface Properties of Nanostructured, Porous ZnO Thin Films Prepared by Direct Current Reactive Magnetron Sputtering

In this paper, the results of detailed X-ray photoelectron spectroscopy (XPS) studies combined with atomic force microscopy (AFM) investigation concerning the local surface chemistry and morphology of nanostructured ZnO thin films are presented. They have been deposited by direct current (DC) reactive magnetron sputtering under variable absolute Ar/O2 flows (in sccm): 3:0.3; 8:0.8; 10:1; 15:1.5; 20:2, and 30:3, respectively. The XPS studies allowed us to obtain the information on: (1) the relative concentrations of main elements related to their surface nonstoichiometry; (2) the existence of undesired C surface contaminations; and (3) the various forms of surface bondings. It was found that only for the nanostructured ZnO thin films, deposited under extremely different conditions, i.e., for Ar/O2 flow ratio equal to 3:0.3 and 30:3 (in sccm), respectively, an evident and the most pronounced difference had been observed. The same was for the case of AFM experiments. What is crucial, our experiments allowed us to find the correlation mainly between the lowest level of C contaminations and the local surface morphology of nanostructured ZnO thin films obtained at the highest Ar/O2 ratio (30:3), for which the densely packaged (agglomerated) nanograins were observed, yielding a smaller surface area for undesired C adsorption. The obtained information can help in understanding the reason of still rather poor gas sensor characteristics of ZnO based nanostructures including the undesired ageing effect, being of a serious barrier for their potential application in the development of novel gas sensor devices.
Cleavage of Dinitrogen from Forming Gas by a Titanium Molecular System under Ambient Conditions.

Simple exposure of a hexane solution of [TiCp*Me3 ] (Cp*=η5 -C5 Me5 ) to an atmosphere of commercially available and inexpensive forming gas (H2 /N2 mixture, 13.5-16.5 % of H2 ) at room temperature leads to the methylidene-methylidyne-nitrido cube-type complex [(TiCp*)4 (μ3 -CH)(μ3 -CH2 )(μ3 -N)2 ] via dinitrogen cleavage. This paramagnetic compound reacts with [D1 ]chloroform to give the titanium(IV) methylidyne-nitrido species [(TiCp*)4 (μ3 -CH)2 (μ3 -N)2 ], whereas its one-electron oxidation with AgOTf or [Fe(η5 -C5 H5 )2 ](OTf) (OTf=O3 SCF3 ) yields the diamagnetic ionic derivative [(TiCp*)4 (μ3 -CH)(μ3 -CH2 )(μ3 -N)2 ](OTf). The μ3 -nitrido ligands of the methylidyne-nitrido cubane complex can be protonated with [LutH](OTf) (Lut=2,6-lutidine) or hydrogenated with NH3 ⋅BH3 to afford μ3 -NH imido moieties.
Body Mass Index and the Spontaneous Onset of Parturition

OBJECTIVE: To investigate the relationship between body mass index (BMI) and the onset of parturition throughout gestation. METHODS: This was a secondary analysis of the Maternal-Fetal Medicine Units Network Preterm Prediction Study. Time-to-spontaneous-birth-event (ie, “survival”) methods were used to study the association of BMI with the timing of spontaneous onset of labor throughout gestation with indicated births censored at delivery. A Kaplan-Meier estimate of the probability of spontaneous labor was compared with a log rank test across five categories of BMI (kg/m2): underweight (less than 18.5), normal weight (18.5–24.99), preobese (25–29.99), obese I (30–34.99), and obese II+ (35 or greater). A proportional hazards model was estimated to compare time to spontaneous onset of labor adjusted for multiple variables known to be associated with the onset of labor. RESULTS: Normal-weight women (n=1,054) had a median delivery gestational age of 39 3/7 weeks. Obese II+ women (n=178) had a median delivery gestational age 5 days later than normal-weight women (P<.001). Delivery gestational age of preobese (n=866) and obese I (n=548) women was not significantly different from normal-weight women. Underweight women (n=41) had a median delivery gestational age 5 days earlier than normal-weight women (P<.001). Compared with women with normal BMIs, obese II+ women were significantly less likely and underweight women significantly more likely to enter spontaneous labor at all gestational ages. In the multivariable model, BMI was significantly associated with spontaneous onset of labor throughout pregnancy (BMI [five-unit] adjusted hazard ratio 0.874, 0.829–0.921). CONCLUSION: Body mass index is significantly associated with the likelihood of the spontaneous onset of labor at all gestational ages with gestational age at the time of delivery and BMI being inversely related. This novel observation unifies previous reports focusing on the association of overweight and underweight BMIs and preterm and postterm birth and may inform discussions surrounding elective induction of labor at term.
An approach to human–machine collaboration in innovation

Abstract If a solvable problem is currently unsolved, then something important to a solution is most likely being overlooked. From this simple observation we derive the obscure features hypothesis: every innovative solution is built upon at least one commonly overlooked or new (i.e., obscure) feature of the problem. By using a new definition of a feature as an effect of an interaction, we are able to accomplish five things. First, we are able to determine where features come from and how to search for new ones. Second, we are able to construct mathematical arguments that the set of features of an object is not computably enumerable. Third, we are able to characterize innovative problem solving as looking for a series of interactions that produce the desired effects (i.e., the goal). Fourth, we are able to construct a precise problem-solving grammar that is both human and machine friendly. Fifth, we are able to devise a visual and verbal problem-solving representation that both humans and computers can contribute to as they help counteract each other's problem-solving weaknesses. We show how computers can counter some of the known cognitive obstacles to innovation that humans have. We also briefly discuss ways in which humans can return the favor. We conclude that a promising process for innovative problem solving is a human–computer collaboration in which each partner assists the other in unearthing the obscure features of a problem.
Meta-analysis of three genome-wide association studies identifies two loci that predict survival and treatment outcome in breast cancer

The majority of breast cancers are driven by the female hormone oestrogen via oestrogen receptor (ER) alpha. ER-positive patients are commonly treated with adjuvant endocrine therapy, however, resistance is a common occurrence and aside from ER-status, no unequivocal predictive biomarkers are currently in clinical use. In this study, we aimed to identify constitutional genetic variants influencing breast cancer survival among ER-positive patients and specifically, among endocrine-treated patients. We conducted a meta-analysis of three genome-wide association studies comprising in total 3,136 patients with ER-positive breast cancer of which 2,751 had received adjuvant endocrine therapy. We identified a novel locus (rs992531 at 8p21.2) associated with reduced survival among the patients with ER-positive breast cancer (P = 3.77 × 10−8). Another locus (rs7701292 at 5q21.3) was associated with reduced survival among the endocrine-treated patients (P = 2.13 × 10−8). Interaction analysis indicated that the survival association of rs7701292 is treatment-specific and independent of conventional prognostic markers. In silico functional studies suggest plausible biological mechanisms for the observed survival associations and a functional link between the putative target genes of the rs992531 and rs7701292 (RHOBTB2 and RAB9P1, respectively). We further explored the genetic interaction between rs992531 and rs7701292 and found a significant, treatment-specific interactive effect on survival among ER-positive, endocrine-treated patients (hazard ratio = 6.97; 95% confidence interval, 1.79–27.08, Pinteraction = 0.036). This is the first study to identify a genetic interaction that specifically predicts treatment outcome. These findings may provide predictive biomarkers based on germ line genotype informing more personalized treatment selection.