Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization and Comparison of the Tissue-Related Modules in Human and Mouse

Background Due to the advances of high throughput technology and data-collection approaches, we are now in an unprecedented position to understand the evolution of organisms. Great efforts have characterized many individual genes responsible for the interspecies divergence, yet little is known about the genome-wide divergence at a higher level. Modules, serving as the building blocks and operational units of biological systems, provide more information than individual genes. Hence, the comparative analysis between species at the module level would shed more light on the mechanisms underlying the evolution of organisms than the traditional comparative genomics approaches. Results We systematically identified the tissue-related modules using the iterative signature algorithm (ISA), and we detected 52 and 65 modules in the human and mouse genomes, respectively. The gene expression patterns indicate that all of these predicted modules have a high possibility of serving as real biological modules. In addition, we defined a novel quantity, “total constraint intensity,” a proxy of multiple constraints (of co-regulated genes and tissues where the co-regulation occurs) on the evolution of genes in module context. We demonstrate that the evolutionary rate of a gene is negatively correlated with its total constraint intensity. Furthermore, there are modules coding the same essential biological processes, while their gene contents have diverged extensively between human and mouse. Conclusions Our results suggest that unlike the composition of module, which exhibits a great difference between human and mouse, the functional organization of the corresponding modules may evolve in a more conservative manner. Most importantly, our findings imply that similar biological processes can be carried out by different sets of genes from human and mouse, therefore, the functional data of individual genes from mouse may not apply to human in certain occasions.
$\propto$SVM for learning with label proportions

We study the problem of learning with label proportions in which the training data is provided in groups and only the proportion of each class in each group is known. We propose a new method called proportion-SVM, or $\propto$SVM, which explicitly models the latent unknown instance labels together with the known group label proportions in a large-margin framework. Unlike the existing works, our approach avoids making restrictive assumptions about the data. The $\propto$SVM model leads to a non-convex integer programming problem. In order to solve it efficiently, we propose two algorithms: one based on simple alternating optimization and the other based on a convex relaxation. Extensive experiments on standard datasets show that $\propto$SVM outperforms the state-of-the-art, especially for larger group sizes.
The Power of Ultrasound

During the last 20 years we have witnessed an amazing increase in the application of ultrasonic energy in different fields of science. This is especially true for analytical chemistry. The number ofmanuscripts devoted to almost all kinds of analysis dealing with the uses of ultrasonic energy continues to grow year by year. As the uses of ultrasonication have become increasingly important in analytical chemistry so to has the importance of the type of ultrasonic device chosen to work with. Figure 1.1 shows themost commonultrasonic devices usednowadays in analytical applications.Not all devices perform equally and neither are all intended for the same applications. Therefore, thefirst thing to acquirewhendeveloping analytical chemistrywith the aid of ultrasonication is a knowledge of the differences among the ultrasonic apparatus available, especially of the advantages and disadvantages expected for each one. Therefore, this chapter explains the state-of-the-art of ultrasonic technology as applied to analytical chemistry.
Impact of screening for risk of suicide: randomised controlled trial

Background Concerns have been expressed about the impact that screening for risk of suicide may have on a person's mental health. Aims To examine whether screening for suicidal ideation among people who attend primary care services and have signs of depression increases the short-term incidence of feeling that life is not worth living. Method In a multicentre, single-blind, randomised controlled trial, 443 patients in four general practices were randomised to screening for suicidal ideation or control questions on health and lifestyle (trial registration: ISRCTN84692657). The primary outcome was thinking that life is not worth living measured 10–14 days after randomisation. Secondary outcome measures comprised other aspects of suicidal ideation and behaviour. Results A total of 443 participants were randomised to early (n = 230) or delayed screening (n = 213). Their mean age was 48.5 years (s.d. = 18.4, range 16–92) and 137 (30.9%) were male. The adjusted odds of experiencing thoughts that life was not worth living at follow-up among those randomised to early compared with delayed screening was 0.88 (95% CI 0.66–1.18). Differences in secondary outcomes between the two groups were not seen. Among those randomised to early screening, 37 people (22.3%) reported thinking about taking their life at baseline and 24 (14.6%) that they had this thought 2 weeks later. Conclusions Screening for suicidal ideation in primary care among people who have signs of depression does not appear to induce feelings that life is not worth living.
Fabrication of tunable silica-mineralized nanotubes using flagella as bio-templates

Bacterial flagella are particularly attractive bio-templates for nanotubes due to their tubular structures and small inner and outer diameters. In this work, flagella isolated from Salmonella typhimurium were used as templates for silica-mineralized nanotubes. The process involved pretreatment of flagella with aminopropyltriethoxysilane (APTES), followed by the addition of tetraethoxysilane (TEOS). By controlling the concentration of TEOS and the reaction time, we developed a simple and precise method for creating silica-mineralized flagella nanotubes (SMFNs) with various thicknesses of the silica layer. It is demonstrated that flagella can be utilized for the fabrication of SMFNs with tunable thickness. A thicker silica layer was obtained as the concentration ratio of TEOS and reaction time was increased. The present experimental evidence has shown the feasibility of using such fabrication techniques to manufacture nanotubes without genetic modification of flagella which retain the original morphology.
Phenylephrine enhances glutamate release in the medial prefrontal cortex through interaction with N‐type Ca2+ channels and release machinery

α1‐adrenoceptors (α1‐ARs) stimulation has been found to enhance excitatory processes in many brain regions. A recent study in our laboratory showed that α1‐ARs stimulation enhances glutamatergic transmission via both pre‐ and post‐synaptic mechanisms in layer V/VI pyramidal cells of the rat medial prefrontal cortex (mPFC). However, a number of pre‐synaptic mechanisms may contribute to α1‐ARs‐induced enhancement of glutamate release. In this study, we blocked the possible post‐synaptic action mediated by α1‐ARs to investigate how α1‐ARs activation regulates pre‐synaptic glutamate release in layer V/VI pyramidal neurons of mPFC. We found that the α1‐ARs agonist phenylephrine (Phe) induced a significant enhancement of glutamatergic transmission. The Phe‐induced potentiation was mediated by enhancing pre‐synaptic glutamate release probability and increasing the number of release vesicles via a protein kinase C‐dependent pathway. The mechanisms of Phe‐induced potentiation included interaction with both glutamate release machinery and N‐type Ca2+ channels, probably via a pre‐synaptic Gq/phospholipase C/protein kinase C pathway. Our results may provide a cellular and molecular mechanism that helps explain α1‐ARs‐mediated influence on PFC cognitive functions.
Unmasking the Metabolite Signature of Bladder Cancer: A Systematic Review

Bladder cancer (BCa) research relying on Omics approaches has increased over the last few decades, improving the understanding of BCa pathology and contributing to a better molecular classification of BCa subtypes. To gain further insight into the molecular profile underlying the development of BCa, a systematic literature search was performed in PubMed until November 2023, following the PRISMA guidelines. This search enabled the identification of 25 experimental studies using mass spectrometry or nuclear magnetic resonance-based approaches to characterize the metabolite signature associated with BCa. A total of 1562 metabolites were identified to be altered by BCa in different types of samples. Urine samples displayed a higher likelihood of containing metabolites that are also present in bladder tumor tissue and cell line cultures. The data from these comparisons suggest that increased concentrations of L-isoleucine, L-carnitine, oleamide, palmitamide, arachidonic acid and glycoursodeoxycholic acid and decreased content of deoxycytidine, 5-aminolevulinic acid and pantothenic acid should be considered components of a BCa metabolome signature. Overall, molecular profiling of biological samples by metabolomics is a promising approach to identifying potential biomarkers for early diagnosis of different BCa subtypes. However, future studies are needed to understand its biological significance in the context of BCa and to validate its clinical application.
Trehalose Maintains Vitality of Mouse Epididymal Epithelial Cells and Mediates Gene Transfer

In the present study, trehalose was utilized to improve primary culture of mouse epididymal epithelial cells in vitro, and to enhance naked DNA delivery in epididymis in vivo. During the six-day culture, the proliferation activity of the cells in the medium with addition of trehalose was higher than that of those cells cultured in absence of trehalose (p<0.01). To determine the optimal concentration for cell proliferation, a series of trehalose concentrations (0, 60, 120, 180 mM) were tested, and the result indicated that the cell in the medium with 120 mM trehalose showed the highest proliferation potential. The epididymis epithelial cells were cultured in the medium containing 120 mM trehalose upon 16th passage, and they continued expressing markers of epididymal epithelial cell, such as rE-RABP, AR and ER-beta. Our study also indicated that trehalose concentrations of 120–240 mM, especially 180 mM, could effectively enhance DNA delivery into the mouse epididymis epithelial cell in vitro. Moreover, trehalose could induce in vivo expression of exogenous DNA in epididymal epithelial cells and help to internalize plasmid into sperm,which did not influence motility of sperm when the mixture of trehalose (180 mM) and DNA was injected into epididymal lumen through efferent tubule. This study suggested that trehalose, as an effective and safer reagent, could be employed potentially to maintain vitality of mouse epididymal epthetial cells during long-term culture in vitro and to mediate in vitro and in vivo gene transfer.
Risk Factors for Developing Metachronous Superficial Gastric Epithelial Neoplasms after Endoscopic Submucosal Dissection

Background: Although endoscopic submucosal dissection (ESD) provides a high rate of curative resection, the remaining gastric mucosa after ESD is at risk for metachronous superficial gastric epithelial neoplasms (MSGENs). It leaves room for risk factors for developing MSGENs after ESD. This study aimed to identify clinicopathological risk factors for the occurrence of MSGENs, and to evaluate the association of Helicobacter pylori (H. pylori) with the MSGENs. Methods: We conducted a retrospective cohort study including 369 patients with 382 lesions that underwent ESD for adenoma/early gastric cancer. Results: Twenty-seven MSGENs occurred. The subjects were divided into MSGEN and not-MSGEN groups. There was a significantly higher frequency of histological intestinal metaplasia (HIM) and initial neoplasm location in the upper or middle parts (INUM) in the MSGEN group. The HIM and INUM groups had a significantly higher cumulative incidence of MSGENs. We compared 27 patients from the MSGEN group and 27 patients from the not-MSGEN group that were matched to the MSGEN group for variables including HIM and INUM. There was a significantly higher frequency of the spontaneous disappearance of H. pylori in the MSGEN group. Conclusions: HIM, INUM, and the spontaneous disappearance of H. pylori may be clinicopathological risk factors for developing MSGENs after ESD.
Multiplex Brain Proteomic Analysis Revealed the Molecular Therapeutic Effects of Buyang Huanwu Decoction on Cerebral Ischemic Stroke Mice

Stroke is the second-leading cause of death worldwide, and tissue plasminogen activator (TPA) is the only drug used for a limited group of stroke patients in the acute phase. Buyang Huanwu Decoction (BHD), a traditional Chinese medicine prescription, has long been used for improving neurological functional recovery in stroke. In this study, we characterized the therapeutic effect of TPA and BHD in a cerebral ischemia/reperfusion (CIR) injury mouse model using multiplex proteomics approach. After the iTRAQ-based proteomics analysis, 1310 proteins were identified from the mouse brain with <1% false discovery rate. Among them, 877 quantitative proteins, 10.26% (90/877), 1.71% (15/877), and 2.62% (23/877) of the proteins was significantly changed in the CIR, BHD treatment, and TPA treatment, respectively. Functional categorization analysis showed that BHD treatment preserved the integrity of the blood–brain barrier (BBB) (Alb, Fga, and Trf), suppressed excitotoxicity (Grm5, Gnai, and Gdi), and enhanced energy metabolism (Bdh), thereby revealing its multiple effects on ischemic stroke mice. Moreover, the neurogenesis marker doublecortin was upregulated, and the activity of glycogen synthase kinase 3 (GSK-3) and Tau was inhibited, which represented the neuroprotective effects. However, TPA treatment deteriorated BBB breakdown. This study highlights the potential of BHD in clinical applications for ischemic stroke.
A Theory of Debugging Plans and Interpretations

We present a theory of debugging applicable for planning and interpretation problems. The debugger analyzes causal explanations for why a bug arises to locate the underlying assumptions upon which the bug depends. A bug is repaired by replacing assumptions, using a small set of domain-independent debugging strategies that reason about the causal explanations and domain models that encode the effects of events. Our analysis of the planning and interpretation tasks indicates that only a small set of assumptions and associated repair strategies are needed to handle a wide range of bugs over a large class of domains. Our debugging approach extends previous work in both debugging and domain-independent planning. The approach, however, is computationally expensive and so is used in the context of the Generate, Test and Debug paradigm, in which the debugger is used only if the heuristic generator produces an incorrect hypothesis.
SPHINGOSINE 1-PHOSPHATE ( S 1 P ) BIOLOGY AND ITS RELEVANCE TO MULTIPLE SCLEROSIS PATHOLOGY

Fingolimod (FTY720) is a first-in-class orally bioavailable compound that has shown efficacy in advanced clinical trials for the treatment of multiple sclerosis (MS). In vivo, fingolimod is phosphorylated to form fingolimod-phosphate, which resembles naturally occurring sphingosine 1-phosphate (S1P), an extracellular lipid mediator whose major effects are mediated by cognate G protein-coupled receptors. There are at least five S1P receptor subtypes, known as S1P1–5, four of which bind fingolimod-phosphate. These receptors are expressed on a wide range of cells that are involved in many biological processes relevant to MS. S1P1 plays a key role in the immune system, regulating lymphocyte egress from lymphoid tissues into the circulation. Fingolimodphosphate initially activates lymphocyte S1P1 via high-affinity receptor binding, yet subsequently induces S1P1 down-regulation that prevents lymphocyte egress from lymphoid tissues, thereby reducing autoaggressive lymphocyte infiltration into the central nervous system (CNS). S1P receptors are also expressed by many CNS cell types and have been shown to influence cell proliferation, morphology and migration. Fingolimod crosses the blood–brain barrier and may therefore have direct CNS effects, distinguishing it from immunologically targeted MS therapies. Prophylactic administration of fingolimod to animals with experimental autoimmune encephalitis (EAE), a model of MS, completely prevents development of EAE features, while therapeutic administration significantly reduces clinical severity of EAE. Therapeutic efficacy observed in animal studies has been substantiated in phase 2 and phase 3 trials involving patients with relapsing or relapsing-remitting MS.
Using portable XRF to infer adularia halos within the Waihi Au-Ag system, New Zealand

Waihi Au-Ag mineralization is vein hosted within a relatively homogeneous andesite body. Geochemical exploration targets adularia and pathfinder (As, Sb, Hg etc.) anomalies. Adularia is formed as an alteration product of feldspars during hydrothermal alteration and occurs in anomalous concentrations near Au-Ag mineralization. This paper aims to test the potential of portable X-ray fluorescence (pXRF) to infer and map adularia and As anomalies. The pXRF was first tested on standards (CRM and ILD), it yielded accurate and precise data for most of the elements of interest (r2 > 0.9 and APD < 10%). The second stage applied the pXRF directly on core, most elements were negatively affected, but still to a usable degree of accuracy. As was particularly effected due to its heterogeneous distribution (APD 46%). Lastly, we applied the pXRF to a suite of 300 Favona samples, their K/Al value were used as a proxy for adularia presence. XRD analysis carried out on 60 samples was used to validate adularias presence or absence. When combined with pXRF data we found a K/Al value above 0.4 generally indicated a sample contained adularia. Therefore, with further work, the pXRF could be independently used to infer adularia alteration in the Waihi setting.
Spatially variable coevolution between a haemosporidian parasite and the MHC of a widely distributed passerine

parasite and the MHC of a widely distributed passerine Matthew R. Jones, Zachary A. Cheviron & Matthew D. Carling Department of Zoology and Physiology, Berry Biodiversity Conservation Center, University of Wyoming, 1000 E. University Ave., Dept. 4304, Laramie, Wyoming 82071 Department of Animal Biology, School of Integrative Biology, University of Illinois Urbana-Champaign, 505 South Goodwin Ave., Urbana, Illinois 61801
Bronchial Hyperresponsiveness to Methacholine and AMP in Children With Atopic Asthma

Purpose Bronchial hyperresponsiveness (BHR) is typically measured by bronchial challenge tests that employ direct stimulation by methacholine or indirect stimulation by adenosine 5'-monophosphate (AMP). Some studies have shown that the AMP challenge test provides a better reflection of airway inflammation, but few studies have examined the relationship between the AMP and methacholine challenge tests in children with asthma. We investigated the relationship between AMP and methacholine testing in children and adolescents with atopic asthma. Methods The medical records of 130 children with atopic asthma (mean age, 10.63 years) were reviewed retrospectively. Methacholine and AMP test results, spirometry, skin prick test results, and blood tests for inflammatory markers (total IgE, eosinophils [total count, percent of white blood cells]) were analyzed. Results The concentration of AMP that induces a 20% decline in forced expiratory volume in 1 second [FEV1] (PC20) of methacholine correlated with the PC20 of AMP (r2=0.189, P<0.001). No significant differences were observed in the levels of inflammatory markers (total eosinophil count, eosinophil percentage, and total IgE) between groups that were positive and negative for BHR to methacholine. However, significant differences in inflammatory markers were observed in groups that were positive and negative for BHR to AMP (log total eosinophil count, P=0.023; log total IgE, P=0.020, eosinophil percentage, P<0.001). In contrast, body mass index (BMI) was significantly different in the methacholine positive and negative groups (P=0.027), but not in the AMP positive and negative groups (P=0.62). The PC20 of methacholine correlated with FEV1, FEV1/forced vital capacity (FVC), and maximum mid-expiratory flow (MMEF) (P=0.001, 0.011, 0.001, respectively), and the PC20 of AMP correlated with FEV1, FEV1/FVC, and MMEF (P=0.008, 0.046, 0.001, respectively). Conclusions Our results suggest that the AMP and methacholine challenge test results correlated well with respect to determining BHR. The BHR to AMP more likely implicated airway inflammation in children with atopic asthma. In contrast, the BHR to methacholine was related to BMI.
Increased Mortality from Lung Cancer and Bronchiectasis in Young Adults after Exposure to Arsenic in Utero and in Early Childhood

Arsenic in drinking water is an established cause of lung cancer, and preliminary evidence suggests that ingested arsenic may also cause nonmalignant lung disease. Antofagasta is the second largest city in Chile and had a distinct period of very high arsenic exposure that began in 1958 and lasted until 1971, when an arsenic removal plant was installed. This unique exposure scenario provides a rare opportunity to investigate the long-term mortality impact of early-life arsenic exposure. In this study, we compared mortality rates in Antofagasta in the period 1989–2000 with those of the rest of Chile, focusing on subjects who were born during or just before the peak exposure period and who were 30–49 years of age at the time of death. For the birth cohort born just before the high-exposure period (1950–1957) and exposed in early childhood, the standardized mortality ratio (SMR) for lung cancer was 7.0 [95% confidence interval (CI), 5.4–8.9; p < 0.001] and the SMR for bronchiectasis was 12.4 (95% CI, 3.3–31.7; p < 0.001). For those born during the high-exposure period (1958–1970) with probable exposure in utero and early childhood, the corresponding SMRs were 6.1 (95% CI, 3.5–9.9; p < 0.001) for lung cancer and 46.2 (95% CI, 21.1–87.7; p < 0.001) for bronchiectasis. These findings suggest that exposure to arsenic in drinking water during early childhood or in utero has pronounced pulmonary effects, greatly increasing subsequent mortality in young adults from both malignant and nonmalignant lung disease.