Miracle-dz/UniFAR-FTUs huggingface dataset:
CD31‐labeled circulating endothelial cells as predictor in anlotinib‐treated non‐small‐cell lung cancer: Analysis on ALTER‐0303 study

Our previous studies revealed that the level of activated circulating endothelial cells (aCECs) was correlated with the progression‐free survival (PFS) in antiangiogenesis therapy. Anlotinib displayed affirmatory efficacies in several clinical trials of non‐small‐cell lung cancer (NSCLC). To find a marker predicting the efficacy of anlotinib treatment, we investigated the correlations of aCECs with PFS and overall survival (OS) in patients with NSCLC treated with anlotinib and the impact of anlotinib on human umbilical vascular endothelial cells (HUVECs). The blood samples of 78 patients with NSCLC were collected. aCECs were identified by flow cytometry as CD45−/CD146+/CD31+ cells and CD45−/CD146+/CD105+ cells. The mean value of baseline aCECs counts was defined as the cutoff value, according to which patients were divided into high and low baseline groups. Statistical correlation between high baseline CD31‐labeled aCECs counts and number of metastatic lesions (>3) (χ2 = 4.905, P = .027) was analyzed. The 49 patients treated with anlotinib were stratified according to the ratio of minimal aCECs counts at any time points to baseline (aCECs min/baseline) as <1 or ≥1. Interestingly, the patients with aCECs (CD31) min/baseline <1 displayed longer PFS [HR = 0.439, 95%CI (0.211‐0.912), P = . 023]. The biological effect of anlotinib on HUVECs was investigated using MTT assays. Western blot analysis was conducted to evaluate the expression levels of CD31 and CD105 under anlotinib treatment and the underlying mechanisms. In vitro experiment data demonstrated that CD31 exhibited more sensitive changes than CD105 under anlotinib treatment through PI3K‐AKT pathway. Thus, our finding provides new insights into the mechanism by which the CD31‐labeled aCECs are a more sensitive marker for predicting the efficiency of anlotinib treatment.
Peptidomic analysis of endogenous plasma peptides from patients with pancreatic neuroendocrine tumours

Rationale Diagnosis of pancreatic neuroendocrine tumours requires the study of patient plasma with multiple immunoassays, using multiple aliquots of plasma. The application of mass spectrometry based techniques could reduce the cost and amount of plasma required for diagnosis. Methods Plasma samples from two patients with pancreatic neuroendocrine tumours were extracted using an established acetonitrile‐based plasma peptide enrichment strategy. The circulating peptidome was characterised using nano and high flow rate liquid chromatography/mass spectrometry (LC/MS) analyses. To assess the diagnostic potential of the analytical approach, a large sample batch (68 plasmas) from control subjects, and aliquots from subjects harbouring two different types of pancreatic neuroendocrine tumour (insulinoma and glucagonoma), were analysed using a 10‐min LC/MS peptide screen. Results The untargeted plasma peptidomics approach identified peptides derived from the glucagon prohormone, chromogranin A, chromogranin B and other peptide hormones and proteins related to control of peptide secretion. The glucagon prohormone derived peptides that were detected were compared against putative peptides that were identified using multiple antibody pairs against glucagon peptides. Comparison of the plasma samples for relative levels of selected peptides showed clear separation between the glucagonoma and the insulinoma and control samples. Conclusions The combination of the organic solvent extraction methodology with high flow rate analysis could potentially be used to aid diagnosis and monitor treatment of patients with functioning pancreatic neuroendocrine tumours. However, significant validation will be required before this approach can be clinically applied.
Bacterial Toxins and Targeted Brain Therapy: New Insights from Cytotoxic Necrotizing Factor 1 (CNF1)

Pathogenic bacteria produce toxins to promote host invasion and, therefore, their survival. The extreme potency and specificity of these toxins confer to this category of proteins an exceptionally strong potential for therapeutic exploitation. In this review, we deal with cytotoxic necrotizing factor (CNF1), a cytotoxin produced by Escherichia coli affecting fundamental cellular processes, including cytoskeletal dynamics, cell cycle progression, transcriptional regulation, cell survival and migration. First, we provide an overview of the mechanisms of action of CNF1 in target cells. Next, we focus on the potential use of CNF1 as a pharmacological treatment in central nervous system’s diseases. CNF1 appears to impact neuronal morphology, physiology, and plasticity and displays an antineoplastic activity on brain tumors. The ability to preserve neural functionality and, at the same time, to trigger senescence and death of proliferating glioma cells, makes CNF1 an encouraging new strategy for the treatment of brain tumors.
The Cellular p53 Inhibitor MDM2 and the Growth Factor Receptor FLT3 as Biomarkers for Treatment Responses to the MDM2-Inhibitor Idasanutlin and the MEK1 Inhibitor Cobimetinib in Acute Myeloid Leukemia

The tumor suppressor protein p53 is inactivated in a large variety of cancer cells. Cellular p53 inhibitors like the mouse double minute 2 homolog (MDM2) commonly suppress the p53 function in acute myeloid leukemia (AML). Moreover, fms like tyrosine kinase 3 (FLT3) growth factor signaling pathways including the mitogen-activated kinase (MAPK) cascade (RAS-RAF-MEK-ERK) are highly active in AML cells. Consequently, the combined administration of MDM2 and MEK inhibitors may present a promising anti-leukemic treatment strategy. Here we assessed the MDM2 antagonist idasanutlin and the MEK1 inhibitor cobimetinib as single agents and in combination in a variety of AML cell lines and primary AML blast cells for their ability to induce apoptosis and cell death. AML cell lines and blast cells comprised all major AML subtypes based on the mutational status of TP53, FLT3 and NPM1 genes. We observed a considerably varying anti-leukemic efficacy of idasanutlin and cobimetinib. AML cells with high sensitivity to the single compounds as well as to the combined treatment emerged with normal karyotype, wild-type TP53 and elevated FLT3 and MDM2 protein levels. Our data indicate that AML cells with normal karyotype (NK) and wild-type status of TP53 with elevated FLT3 and MDM2 expression emerge to be most sensitive to the combined treatment with cobimetinib and idasanutlin. FLT3 and MDM2 are biomarkers for treatment response to idasanutlin and cobimetinib in AML.
Ultrastructure and differentiation of the larval esophageal muscle cells of the starfish Pisaster ochraceus

The muscle cells that cause constriction of the starfish larval esophagus (esophageal muscle cells) are one of the first cell types to express their differentiated morphological characteristics during development. Ultrastructurally these muscle cells resemble vertebrate and invertebrate smooth muscles. They contain a nucleus, a Golgi apparatus, contractile myofilaments, hemidesmosome‐like structures, and what appears to be a simple sarcoplasmic reticulum. In asteroid embryos, this muscle layer originates during mouth formation when mesenchyme cells migrate from the tips of the coeloms to the esophagus. Once there, they elongate, forming processes. Over the next few days, the processes become filled with arrays of longitudinally arranged thick and thin myofilaments and thin sacs of smooth endoplasmic reticulum. The latter appear between the bundles of contractile filaments and the cell membranes. Contractile activity begins at approximately this time. The cisternae may represent a sarcoplasmic reticulum that is required for contraction. The majority of the esophageal muscle cell processes extend around the circumference of the developing esophagus, but occasional cells may be oriented in other directions. The latter cells are always farther away from the basal lamina and probably have little or no contact with it. Contact with basal lamina may serve to direct the migration of the cells and the orientation of the processes. J. Morphol. 237:1–18, 1998. © 1998 Wiley‐Liss, Inc.
Diagnostic and Prognostic Potential of MicroRNA Maturation Regulators Drosha, AGO1 and AGO2 in Urothelial Carcinomas of the Bladder

Bladder cancer still requires improvements in diagnosis and prognosis, because many of the cases will recur and/or metastasize with bad outcomes. Despite ongoing research on bladder biomarkers, the clinicopathological impact and diagnostic function of miRNA maturation regulators Drosha and Argonaute proteins AGO1 and AGO2 in urothelial bladder carcinoma remain unclear. Therefore, we conducted immunohistochemical investigations of a tissue microarray composed of 112 urothelial bladder carcinomas from therapy-naïve patients who underwent radical cystectomy or transurethral resection and compared the staining signal with adjacent normal bladder tissue. The correlations of protein expression of Drosha, AGO1 and AGO2 with sex, age, tumor stage, histological grading and overall survival were evaluated in order to identify their diagnostic and prognostic potential in urothelial cancer. Our results show an upregulation of AGO1, AGO2 and Drosha in non-muscle-invasive bladder carcinomas, while there was increased protein expression of only AGO2 in muscle-invasive bladder carcinomas. Moreover, we were able to differentiate between non-muscle-invasive and muscle-invasive bladder carcinoma according to AGO1 and Drosha expression. Finally, despite Drosha being a discriminating factor that can predict the probability of overall survival in the Kaplan–Meier analysis, AGO1 turned out to be independent of all clinicopathological parameters according to Cox regression. In conclusion, we assumed that the miRNA processing factors have clinical relevance as potential diagnostic and prognostic tools for bladder cancer.
What Temperature of Coffee Exceeds the Pain Threshold? Pilot Study of a Sensory Analysis Method as Basis for Cancer Risk Assessment

The International Agency for Research on Cancer (IARC) evaluates “very hot (>65 °C) beverages” as probably carcinogenic to humans. However, there is a lack of research regarding what temperatures consumers actually perceive as “very hot” or as “too hot”. A method for sensory analysis of such threshold temperatures was developed. The participants were asked to mix a very hot coffee step by step into a cooler coffee. Because of that, the coffee to be tasted was incrementally increased in temperature during the test. The participants took a sip at every addition, until they perceive the beverage as too hot for consumption. The protocol was evaluated in the form of a pilot study using 87 participants. Interestingly, the average pain threshold of the test group (67 °C) and the preferred drinking temperature (63 °C) iterated around the IARC threshold for carcinogenicity. The developed methodology was found as fit for the purpose and may be applied in larger studies.
At Least Bias Is Bipartisan: A Meta-Analytic Comparison of Partisan Bias in Liberals and Conservatives

Both liberals and conservatives accuse their political opponents of partisan bias, but is there empirical evidence that one side of the political aisle is indeed more biased than the other? To address this question, we meta-analyzed the results of 51 experimental studies, involving over 18,000 participants, that examined one form of partisan bias—the tendency to evaluate otherwise identical information more favorably when it supports one’s political beliefs or allegiances than when it challenges those beliefs or allegiances. Two hypotheses based on previous literature were tested: an asymmetry hypothesis (predicting greater partisan bias in conservatives than in liberals) and a symmetry hypothesis (predicting equal levels of partisan bias in liberals and conservatives). Mean overall partisan bias was robust (r = .245), and there was strong support for the symmetry hypothesis: Liberals (r = .235) and conservatives (r = .255) showed no difference in mean levels of bias across studies. Moderator analyses reveal this pattern to be consistent across a number of different methodological variations and political topics. Implications of the current findings for the ongoing ideological symmetry debate and the role of partisan bias in scientific discourse and political conflict are discussed.
Embryonic staging and external features of development of the Chimaeroid fish, Callorhinchus milii (Holocephali, Callorhinchidae)

The development of Callorhinchus milii, a primitive chondrichthyan fish (Subclass Holocephali) is described in detail based on a complete series of embryos from stage 17 to hatching. The external features of these specimens, in comparison with other chondrichthyan embryos, are used to establish the first staging table for any chimaeroid species. Each stage of C. milii is defined by a suite of morphological characters in addition to total length, including the number of somites, extent of external pigmentation, eye size and shape, head flexure, heart morphology, and size and shape of paired and unpaired fins. Particular attention is given to features of the gill arches and associated structures, including external gill filaments and the opercular flap. Embryos of this species also possess a transient rostral bulb, a feature unique to chimaeroids.
Orientation Encoding and Viewpoint Invariance in Face Recognition: Inferring Neural Properties from Large-Scale Signals

Viewpoint-invariant face recognition is thought to be subserved by a distributed network of occipitotemporal face-selective areas that, except for the human anterior temporal lobe, have been shown to also contain face-orientation information. This review begins by highlighting the importance of bilateral symmetry for viewpoint-invariant recognition and face-orientation perception. Then, monkey electrophysiological evidence is surveyed describing key tuning properties of face-selective neurons—including neurons bimodally tuned to mirror-symmetric face-views—followed by studies combining functional magnetic resonance imaging (fMRI) and multivariate pattern analyses to probe the representation of face-orientation and identity information in humans. Altogether, neuroimaging studies suggest that face-identity is gradually disentangled from face-orientation information along the ventral visual processing stream. The evidence seems to diverge, however, regarding the prevalent form of tuning of neural populations in human face-selective areas. In this context, caveats possibly leading to erroneous inferences regarding mirror-symmetric coding are exposed, including the need to distinguish angular from Euclidean distances when interpreting multivariate pattern analyses. On this basis, this review argues that evidence from the fusiform face area is best explained by a view-sensitive code reflecting head angular disparity, consistent with a role of this area in face-orientation perception. Finally, the importance is stressed of explicit models relating neural properties to large-scale signals.
Prevalence and determinants of hypertension among adult population in Nepal: Data from Nepal Demographic and Health Survey 2016

Like other developing countries, Nepal is currently going through epidemiological transition along with rising burden of Non-communicable Diseases. However, since 2013, no study investigated the prevalence and determinants of hypertension in Nepal involving nationally representative sample. Therefore, this study aimed to find out the current prevalence of hypertension in Nepal and its determinants using the latest nationally representative data obtained from Nepal Demographic and Health Survey (NDHS) 2016. The NDHS 2016 collected data on hypertension from 13,304 men and women aged 18 years and above from 5,520 urban and 5,970 rural households covering seven administrative provinces and three ecological zones. Participants were considered as hypertensive when their systolic blood pressure was ≥140 mmHg and/or diastolic blood pressure was ≥90 mmHg and/or they reported taking antihypertensive medication. A total of 19.9% study participants were diagnosed as hypertensive of which majority were male (male-24.3%, female-16.9%), ever married (ever married-21.7%, unmarried-6.1%) and residents of urban area (urban-20.9%, rural-18.3%). Hypertension prevalence has shown growing trend with the increase of age. This prevalence was also higher among rich and overweight/obese individuals. In multivariable logistic regression analysis, older age, male gender, better education, residence at urban area and province 4 and 5 and being overweight/obese were found positive association with having hypertension. When the determinants of hypertension were stratified by sex of the participants, difference was observed in case of age group, education and place of residence. As one out of every five individuals in Nepal are hypertensive, public health initiatives are immediately required for prevention and control of hypertension to reduce mortality and morbidity associated with this progressive disease.
What works to promote walking at the population level? A systematic review

Objective Interventions to promote walking have focused on individual or group-based approaches, often via the randomised controlled trial design. Walking can also be promoted using population health approaches. We systematically reviewed the effectiveness of population approaches to promote walking among individuals and populations. Design A systematic review. Data sources 10 electronic databases searched from January 1990 to March 2017. Eligibility criteria Eligibility criteria include pre-experimental and postexperimental studies of the effects of population interventions to change walking, and the effects must have been compared with a ‘no intervention’, or comparison group/area/population, or variation in exposure; duration of ≥12 months of follow up; participants in free-living populations; and English-language articles. Results 12 studies were identified from mostly urban high-income countries (one focusing on using tax, incentivising the loss of parking spaces; and one using policy only, permitting off-leash dogs in city parks). Five studies used mass media with either environment (n=2) or community (n=3) approaches. Four studies used environmental changes that were combined with policies. One study had scaled up school-based approaches to promote safe routes to schools. We found mass media, community initiatives and environmental change approaches increased walking (range from 9 to 75 min/week).
Influence of vagal control on sex-related differences in left ventricular mechanics and hemodynamics.

Left ventricular (LV) twist mechanics differ between men and women during acute physiological stress, which may be partly mediated by sex differences in autonomic control. While men appear to have greater adrenergic control of LV twist, the potential contribution of vagal modulation to sex differences in LV twist remains unknown. Therefore, the present study examined the role of vagal control on sex differences in LV twist during graded lower body negative pressure (LBNP) and supine cycling. On two separate visits, LV mechanics were assessed using two-dimensional speckle-tracking echocardiography in 18 men (22 ± 2 yr) and 17 women (21 ± 4 yr) during -40- and -60-mmHg LBNP and 25% and 50% of peak supine cycling workload with and without glycopyrrolate (vagal blockade). LV twist was not different at baseline but was greater in women during -60 mmHg in both control (women: 16.0 ± 3.4° and men: 12.9 ± 2.3°, P = 0.004) and glycopyrrolate trials (women: 17.7 ± 5.9° and men: 13.9 ± 3.3°, P < 0.001) due to greater apical rotation during control (women: 11.9 ± 3.6° and men: 7.8 ± 1.5°, P < 0.001) and glycopyrrolate (women: 11.6 ± 4.9° and men: 7.1 ± 3.6°, P = 0.009). These sex differences in LV twist consistently coincided with a greater LV sphericity index (i.e., ellipsoid geometry) in women compared with men. In contrast, LV twist did not differ between the sexes during exercise with or without glycopyrrolate. In conclusion, women have augmented LV twist compared with men during large reductions to preload, even during vagal blockade. As such, differences in vagal control do not appear to contribute to sex differences in the LV twist responses to physiological stress, but they may be related to differences in ventricular geometry. NEW & NOTEWORTHY This is the first study to specifically examine the role of vagal autonomic control on sex-related differences in left ventricular (LV) mechanics. Contrary to our hypothesis, vagal control does not appear to primarily determine sex differences in LV mechanical or hemodynamic responses to acute physiological stress. Instead, differences in LV geometry may be a more important contributor to sex differences in LV mechanics.
Counting with DNA in metabarcoding studies: How should we convert sequence reads to dietary data?

Advances in DNA sequencing technology have revolutionised the field of molecular analysis of trophic interactions and it is now possible to recover counts of food DNA barcode sequences from a wide range of dietary samples. But what do these counts mean? To obtain an accurate estimate of a consumer’s diet should we work strictly with datasets summarising the frequency of occurrence of different food taxa, or is it possible to use the relative number of sequences? Both approaches are applied in the dietary metabarcoding literature, but occurrence data is often promoted as a more conservative and reliable option due to taxa-specific biases in recovery of sequences. Here, we point out that diet summaries based on occurrence data overestimate the importance of food consumed in small quantities (potentially including low-level contaminants) and are sensitive to the count threshold used to define an occurrence. Our simulations indicate that even with recovery biases incorporated, using relative read abundance (RRA) information can provide a more accurate view of population-level diet in many scenarios. The ideas presented here highlight the need to consider all sources of bias and to justify the methods used to interpret count data in dietary metabarcoding studies. We encourage researchers to continue to addressing methodological challenges, and acknowledge unanswered questions to help spur future investigations in this rapidly developing area of research.