jimnoneill/paper-to-field-training huggingface dataset:
[Drug targets discovery based on dynamic signal transduction networks].

Since last century, drug discovery efforts mostly focus on searching for chemicals which can inhibit some specific steps in a well-described disease pathway. However, this kind of highly specific inhibitors can not be effective for complex diseases, like cancer, diabetes, schizophrenia and mental illness. Therefore, we need to rethink the drug discovery and therapeutic strategies. In this review, the strategies of selection of cellular signal transduction networks and their dynamics as the targets for drug discovery and pharmacological treatments will be discussed. The properties and analytical methods of these signal transduction networks, internet sources and software tools for performing these strategies will be described. Strategies and procedures of using network-based drug discovery will be emphasized, including multi-targets drug design and network-based drug discovery.

Topic: Computational Drug Discovery Methods
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Prevalence and Antimicrobial Susceptibility Profile of Salmonella and Shigella among Diarrheic Patients Attending Selected Health Facilities in Addis Ababa, Ethiopia

Diarrhea is one of the important public health problems in developing countries. Salmonella and Shigella species are the major bacterial causal agents of diarrhea. The increasing burden of antimicrobial resistance is posing difficulty in the treatment of these pathogens. This study aimed to assess the occurrence of Salmonella and Shigella in the feces of diarrheic patients receiving health services in Addis Ababa, Ethiopia, and to determine their antimicrobial susceptibility profile. A cross-sectional study involving 13 health centers was conducted where 428 diarrheic patients were recruited. Standard microbiology techniques were used to isolate Salmonella and Shigella from stool samples. In addition, Salmonella isolates were confirmed by polymerase chain reaction (PCR). The Kirby–Bauer disc diffusion method was employed to assess susceptibility to 11 antimicrobials for each of the Salmonella and Shigella isolates. The prevalence of Salmonella and Shigella spp. among diarrheic patients was 8.4%; n = 36 and 5.6%; n = 24, respectively. Thirty (83.3%) of Salmonella isolates were susceptible to all antimicrobials tested, whereas 4 (10.8%) of isolates were resistant to 2 or more antimicrobials and 2 (5.6%) were multidrug resistant. Resistance to ampicillin was recorded in only one (2.7%) of Salmonella isolates; however, resistance to ampicillin was recorded in 12 (50%) of the Shigella isolates. Half of the Shigella isolates (n = 12) were resistant to 2 or more antimicrobials while 5 (20.8%) of them were resistant to 3 or more antimicrobials. The overall rate of resistance to antimicrobials was more common in Shigella compared to Salmonella isolates. In conclusion, Salmonella and Shigella were isolated from the feces of diarrheic patients, with a higher rate of antimicrobial resistance in Shigella isolates, which could make the treatment of shigellosis challenging. Therefore, increasing hygienic practices during food preparation to reduce the burden of Salmonella and Shigella infection and prudent use of antimicrobials are recommended to limit the spread of antimicrobial resistant strains.

Topic: Salmonella and Campylobacter epidemiology
Subfield: Food Science
Field: Agricultural and Biological Sciences
Domain: Life Sciences
Radiofrequency ablation versus percutaneous microwave coagulation therapy for small hepatocellular carcinomas: a retrospective comparative study.

RFA is more useful than PMCT in the treatment of small HCCs because it is minimally invasive and achieves a low local recurrence rate, high survival rate, and extensive necrosis after only a few treatment sessions.

Topic: Hepatocellular Carcinoma Treatment and Prognosis
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Border‐like cell formation mediated by SgPG1 confers aluminum resistance in <i>Stylosanthes guianensis</i>

SUMMARY Stylosanthes is an important forage legume in tropical areas with strong resistance to aluminum (Al) toxicity, though knowledge of mechanisms underlying this resistance remains fragmentary. We found that border‐like cells (BLCs) were constitutively produced surrounding the root tips of all 54 examined Stylosanthes guianensis genotypes, but not the Stylosanthes viscose genotype TF0140. In genotypic comparisons under Al conditions, the S. guianensis genotype RY#2 retained significantly more Al in BLCs and thereby showed higher relative root growth than TF0140. Formation of BLCs accompanied changes in cell wall pectin epitopes and differential expression of genes involved in pectin metabolism, including a polygalacturonase ( SgPG1 ). The expression pattern of SgPG1 was consistent with the formation of BLCs in both RY#2 and TF0140. SgPG1 was localized in cell walls and exhibited high activities mediating demethyl‐esterified homogalacturonan degradation. Overexpressing SgPG1 changed cell wall pectin epitopes, enhanced BLCs production, and Al resistance in both Arabidopsis and Stylosanthes hairy roots. Furthermore, combining protein‐DNA binding assays in vitro and in vivo , a bHLH transcription factor SgbHLH19 was demonstrated to be the upstream regulator of SgPG1 . Our study demonstrates that S. guianensis Al resistance mainly relies on BLCs, whose formation involves cell wall pectin epitope modification by SgPG1.

Topic: Aluminum toxicity and tolerance in plants and animals
Subfield: Plant Science
Field: Agricultural and Biological Sciences
Domain: Life Sciences
Research on the Higher Vocational Medicine Production Technology Cultivation Mode of Modern Apprenticeship Talents based on the Integration of Production and Education

With the continuous development of Chinese economy, people's living standards have been fully improved, while the demand for the use of drugs also showed a rising trend.From the management of pharmaceutical enterprises and the development of regional economy, the further development of modern apprenticeship training mode of pharmaceutical production technology has played a crucial role in pharmaceutical production.In this paper, through the analysis and analysis of Chinese modern apprenticeship training model to promote the situation, in the vocational colleges to carry out modern apprenticeship talent training mode experience, vocational colleges to develop modern apprenticeship training model problems and solutions The three main aspects of the program, aimed at the comprehensive integration of education in the context of a comprehensive scientific and rational production of modern vocational medicine production technology professional modern apprenticeship training model to strengthen the students' drug production and production capacity, so as to Chinese pharmaceutical companies Cultivate professional and practical high-quality personnel, and further promote Chinese pharmaceutical companies to be stable and healthy operation and development.

Topic: Ideological and Political Education
Subfield: Education
Field: Social Sciences
Domain: Social Sciences
Coupled Vibration Response Analysis of Tension Leg Platform Tendon Under Irregular Ocean Wave Action

To analyze the dynamic response of tension leg platform (TLP) tendons under irregular ocean wave action, the governing equations of coupled vibration between the platform and tendon under irregular wave action are established based on Hamilton’s principle and the Kirchhoff hypothesis. Using the spectrum representation–random function method, the power spectral density function of the irregular wave load is derived, and the lateral wave forces at different tendon locations are calculated. The coupled lateral and axial responses of the tendon system are obtained through the fourth-order Runge–Kutta method. Considering the parametric vibrations of both the platform and tendon, the extreme lateral deflection of the tendon is employed as the control index to derive the probability density curves of the tendon deflection under irregular wave load. The results show that the amplitude of the wave load increases gradually along the height of the tendon, with a faster growth rate at locations closer to the water surface. The tendon’s lateral deflection response changes more drastically due to coupled parametric vibration of the platform. Based on 628 complete samples of irregular wave loads, the probability density curve and cumulative distribution curve of the extreme lateral deflection of the tendon under irregular wave loads are obtained. Under typical sea state conditions generated from the P-M wave spectrum, the reliability of the tendon under irregular wave load increases with the initial tension force.

Topic: Vibration and Dynamic Analysis
Subfield: Control and Systems Engineering
Field: Engineering
Domain: Physical Sciences
A Superquadratic Variant of Newton's Method

This paper presents a Q-superquadratically convergent version of Newton's method for solving operator equations in Banach spaces that requires only one operator value and one inverse of the Fréchet derivative per iteration. The R-order of convergence is at least $1+\sqrt{2}$. Both a semilocal and a local analysis of the new method are given. The semilocal analysis is done along the lines of the Newton--Kantorovich theorem and provides sufficient conditions for the existence of a solution and the convergence of the iterates. The Q-superquadratic convergence is obtained by assuming that the second Fréchet derivative is Lipschitz continuous. The local analysis assumes that a solution exists and shows that the method converges from any starting point belonging to an explicitly defined neighborhood of the solution called the ball of attraction. To our knowledge this is the first superquadratically convergent method that requires about the same work per iteration as Newton's method.

Topic: Iterative Methods for Nonlinear Equations
Subfield: Numerical Analysis
Field: Mathematics
Domain: Physical Sciences
High-Concentration Niobium-Substituted WS<sub>2</sub> Basal Domains with Reconfigured Electronic Band Structure for Hydrogen Evolution Reaction

Extrinsically controlling the intrinsic activity and stability of two-dimensional (2D) semiconducting materials by substitutional doping is crucial for energy-related applications. However, an in situ transition-metal doping strategy for uniform and large-area chemical vapor deposited 2D semiconductors remains a formidable challenge. Here, we successfully synthesize highly uniform niobium-substituted tungsten disulfide (Nb-WS<sub>2</sub>) monolayers, with a doping concentration of nearly 7% and sizes reaching 100 μm, through a metal dopant precursor route, using salt-catalyzed chemical vapor deposition (CVD). Our results reveal unusual effects in the structural, optical, electronic, and electrocatalysis characteristics of the Nb-WS<sub>2</sub> monolayer. The Nb dopants readily induce a band restructuring effect, providing the most active site with a hydrogen adsorption energy of 0.175 eV and hence greatly improving its hydrogen evolution activity<sub>.</sub> The combined advantages of the unusual physics and chemistry by in situ CVD doping technique open the possibility in designing 2D-material-based electronics and catalysts of novel functionalities.

Topic: 2D Materials and Applications
Subfield: Materials Chemistry
Field: Materials Science
Domain: Physical Sciences
European Industrial Policy

This survey of European industrial policy aims to set out and explain the great significance of European integration in determining (changes in) structure and performance of industry in the EU. This influence is explored from the policy side by analysing the transformation of the framework within which both EU and Member States' industrial policy can be pursued. Empirical economic analysis is not included because this BEEP Briefing was originally written for a handbook in which other authors were assigned a range of industrial economics subjects. In the last 25 years or so, the transformation is such that the nature and scope of industrial policy at both levels of government has profoundly changed as well. Indeed, the toolkit of measures has shrunk considerably, disciplines have been tightened and the economic policy views behind industrial policy have altered everywhere. The pro-competitive logic of deeper market integration itself is rarely questioned nowadays and industrial policy at the two levels takes on different forms. The survey discusses at some length the division of powers between, and the complementarity of, the Member States' and EU levels of government when it comes to industrial policy, based on a fairly detailed classification of industrial policy instruments. The three building blocks of the wide concept of industrial policy as defined in this BEEP Briefing consist of the EU framework of market integration, EU horizontal industrial policy and its EU sectoral or specific counterpart. Each one is surveyed at the EU level. Preceding these three sections is a discussion of three cross-cutting issues, namely, the indiscriminate use of the 'competitiveness' label in the EU circuit of business and policy makers, the relation between services and EU industrial policy and, finally, that of European infrastructure. One major conclusion is that, today, the incentive structure for industry and industrial markets is dominated by the stringency of the overall EU framework and to some moderate degree by the horizontal approach.

Topic: Economic Growth and Productivity
Subfield: Economics and Econometrics
Field: Economics, Econometrics and Finance
Domain: Social Sciences
Abstract 409: LRRC10 Associates With and Regulates Cardiac Ca <sub>V</sub> 1.2 L-type Ca <sup>2+</sup> Channels, and I195T LRRC10 Variant is Linked to Dilated Cardiomyopathy

Leucine-rich repeat containing (LRR) proteins facilitate protein-protein interactions critical in a number of cellular functions including ion channel regulation. Leucine-rich repeat containing protein 10 (LRRC10), a cardiac-specific protein expressed in zebrafish, mice and humans, is essential for normal cardiac physiology with loss of Lrrc10 in Lrrc10 -/- mice resulting in dilated cardiomyopathy (DCM). However, the mechanism by which LRRC10 contributes to DCM is unknown. Further, the functional role of LRRC10 in the regulation of ion channels in the heart has not been explored. Here we recorded L-type Ca 2+ channel currents (I Ca,L ) from isolated ventricular myocytes of WT and Lrrc10 -/- mice, demonstrating a significant reduction in I Ca,L in Lrrc10 -/- myocytes (-4.9 ± 0.19 pA/pF, n=10) compared to WT (-6.5 ± 0.24 pA/pF, n=8). Co-immunoprecipitation (co-IP) experiments showed an association between LRRC10 and Ca v 1.2 in WT, but not Lrrc10 -/- mouse lysates, with immunocytochemistry studies further demonstrating colocalization of LRRC10 and Ca v 1.2 in isolated ventricular myocytes from wild-type (WT) mice. Additionally, whole exome sequencing revealed a novel homozygous recessive missense variant in LRRC10 , I195T, found in a pediatric DCM patient. To determine whether the I195T variant impacts Ca v 1.2 L-type Ca 2+ channels, whole-cell patch clamp experiments were performed using HEK293 cells transiently expressing the L-type Ca 2+ channel complex (LTCC) alone or with WT or I195T LRRC10. These electrophysiology experiments demonstrated a significant increase in I Ca,L with WT LRRC10 coexpression (-81 ± 5.3 pA/pF, n=12), but a decrease in I Ca,L when I195T (-18.2 ± 3.3 pA/pF, n=9) was coexpressed compared to the LTCC alone (-34.1 ± 2.2 pA/pF, n=17). Parallel surface biotinylation experiments demonstrated that WT and I195T LRRC10 did not alter L-type Ca 2+ channel expression on the plasma membrane, while co-IP experiments using lysates prepared from the transiently transfected HEK293 cells showed the association between Ca v 1.2 and I195T LRRC10 variant. Overall, these findings newly identify LRRC10 as a cardiac-specific component of the Ca v 1.2 macromolecular complex and demonstrate dysregulation of I Ca,L by the DCM associated I195T LRRC10 variant.

Topic: Ion channel regulation and function
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Variations in the origin of the anterior spinal artery in a Colombian population sample

Based on most neuroanatomical descriptions, the anterior spinal artery (ASA) originates from two small vessels of the vertebral arteries, which are anastomosed just before forming the basilar artery. This study aimed to determine and quantify the possible variants of the origin of the ASA and its trajectory in samples of human brain stems. Male brain stems with the superior portion of the spinal cord until myelomera C3 of 23 adult human, and no evident morphological alterations were selected. The brain stems were collected for three years and fixed in a 10% formalin solution at the Anatomy Laboratory of the Universidad de Caldas (Colombia). Five samples (21.7%) had variations in the origin and trajectory of the anterior spinal artery. The variations in the origin of the ASA could generate morphofunctional advantages instead of leading to complications. That is the case when there are two anterior spinal arteries since it would increase tissue perfusion, thus protecting part of the spinal cord from ischemic pathologies. It is essential to consider the variations that may exist in the supply of the anterior region of the spinal cord for clinical and surgical assessments due to variations in its supplied territory.

Topic: Aortic Disease and Treatment Approaches
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Environmental influence and cohort effects in a sexual ornament in the house sparrow, <i>Passer domesticus</i>

Presence of phenotypic variation is necessary for selection to occur, yet processes affecting variation in sexually selected characters in natural populations are poorly understood. Here we examine whether variation in a sexual ornament (badge size) of male house sparrows ( Passer domesticus ) is dependent on individual variation in the conditions during early ontogenetic stages, and whether this variation and the population‐wide effects of external variables such as weather or population size jointly will generate consistent differences among cohorts later in life. Variation in badge size was independent of adult body size, whereas heavier fledglings and fledglings in good body condition developed smaller visible badges as adults. Furthermore, strong cohort‐effects were present, caused by a combined effect of density‐dependence and weather during the early development in the moulting period and autumn after hatching. Thus, badge size is an environmentally‐dependent trait in house sparrows, and likely to be under the influence of both natural and sexual selection.

Topic: Animal Behavior and Reproduction
Subfield: Ecology, Evolution, Behavior and Systematics
Field: Agricultural and Biological Sciences
Domain: Life Sciences
The Effect of Anterior Cruciate Ligament Injury and Reconstruction on Lower Extremity Biomechanics, Coordination, and Variability

Individuals that suffer an ACL injury, and undergo reconstructive surgery are at an increased risk for the development of osteoarthritis and a secondary ACL injury. However, there is no information other than case studies, that has documented the effect of ACL injury on lower extremity biomechanics and coordination, and few studies have assessed asymmetry in these measures relative to noninjured individuals. The purpose of this study was to determine if lower extremity biomechanics and coordination are altered by ACL injury. A second purpose was to determine if differences in bilateral asymmetry in lower extremity biomechanics, coordination, and variability for those with ACL injury are greater than those with no injury. Following ACL injury, we observed an increase in knee valgus (F(2,66) = 3.957, p = 0.024) and hip adduction (F(2,66) = 3.773, p = 0.028) at Initial Ground Contact for both the injured and noninjured limb, as well as a decrease in peak knee varus (F(2, 66) = 5.198, p = 0.008). An increase in peak knee valgus was also observed in the noninjured limb (F(2,66) = 3.768, p = 0.028). This was associated with a decrease in peak knee extension moment (F(2,66) = 4.509, p = 0.015), peak hip flexion moment (F(2,66) = 3.847, p = 0.026), and peak anterior tibial shear force (F(2,66) = 4.530, p = 0.014) for the injured limb. In addition, we observed an alteration in coordination of hip and knee transverse plane motion for the injured limb following ACL injury (F(2,65) = 4.398, p = 0.016). The only differences we observed for asymmetry was for those with ACLR to have greater asymmetry for peak internal knee flexion moment (ZKS = 1.42, p = 0.035) and peak vertical ground reaction force (ZKS = 1.45, p = 0.031). We did not observe any significant difference in asymmetry of lower extremity coordination or variability between groups. Our findings provide evidence for how ACL injury and ACLR may increase an individual's risk for a second ACL injury and the development of osteoarthritis.

Topic: Knee injuries and reconstruction techniques
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Two 2,5-bis(2-pyridinyl)-1,3,4-oxadiazole–metal complexes (<i>M</i>= Cu and Ni)

The reaction of the diazine ligand 3,5-bis(2-pyridinyl)-1,3,4-oxa­diazole (pod, C12H8N4O), with Cu(CF3SO3)2 or Ni(ClO4)2 afforded the title complexes di­aqua­bis­[3,5-bis(2-pyridinyl)-1,3,4-oxa­diazole-N2,N3]copper(II) bis­(tri­fluoro­methane­sul­fon­ate), [Cu(pod)2(H2O)2](CF3SO3)2, and di­aqua­bis­[3,5-bis(2-pyridinyl)-1,3,4-oxa­diazo­le-N2,N3]­nickel(II) diperchlorate, [Ni(pod)2(H2O)2](ClO4)2. Both complexes present a crystallographically centrosymmetric mononuclear cation structure which consists of a six-coordinated CuII or NiII ion with two pod mol­ecules acting as bidentate ligands and two axially coordinated water mol­ecules.

Topic: Metal complexes synthesis and properties
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Effect of Ulinastatin Combined with Somatostatin on Inflammatory Markers, Hemodynamics and Immune Cells in the Treatment of Severe Pancreatitis.

The findings of this study hold substantial clinical implications, potentially influencing treatment protocols and patient management strategies for severe pancreatitis. The integration of ulinastatin combined with somatostatin into standard care protocols could significantly improve treatment outcomes and patient prognosis.

Topic: Pancreatitis Pathology and Treatment
Subfield: Surgery
Field: Medicine
Domain: Health Sciences