Miracle-dz/UniFAR-FTUs huggingface dataset:
Three Distinct Stroma Types in Human Pancreatic Cancer Identified by Image Analysis of Fibroblast Subpopulations and Collagen

Purpose: Cancer-associated fibroblasts have emerged to be highly heterogenous and can play multifaceted roles in dictating pancreatic ductal adenocarcinoma (PDAC) progression, immunosuppression, and therapeutic response, highlighting the need for a deeper understanding of stromal heterogeneity between patients and even within a single tumor. We hypothesized that image analysis of fibroblast subpopulations and collagen in PDAC tissues might guide stroma-based patient stratification to predict clinical outcomes and tumor characteristics. Experimental Design: A novel multiplex IHC-based image analysis system was established to digitally differentiate fibroblast subpopulations. Using whole-tissue slides from 215 treatment-naïve PDACs, we performed concurrent quantification of principal fibroblast subpopulations and collagen and defined three stroma types: collagen-rich stroma, fibroblast activation protein α (FAP)-dominant fibroblast-rich stroma, and α smooth muscle actin (ACTA2)-dominant fibroblast-rich stroma. These stroma types were assessed for the associations with cancer-specific survival by multivariable Cox regression analyses and with clinicopathologic factors, including CD8+ cell density. Results: FAP-dominant fibroblasts and ACTA2-dominant fibroblasts represented the principal distinct fibroblast subpopulations in tumor stroma. Stroma types were associated with patient survival, SMAD4 status, and transcriptome signatures. Compared with FAP-dominant fibroblast-rich stroma, collagen-rich stroma correlated with prolonged survival [HR, 0.57; 95% confidence interval (CI), 0.33–0.99], while ACTA2-dominant fibroblast-rich stroma exhibited poorer prognosis (HR, 1.65; 95% CI, 1.06–2.58). FAP-dominant fibroblast-rich stroma was additionally characterized by restricted CD8+ cell infiltrates and intense neutrophil infiltration. Conclusions: This study identified three distinct stroma types differentially associated with survival, immunity, and molecular features, thereby underscoring the importance of stromal heterogeneity in subtyping pancreatic cancers and supporting the development of antistromal therapies.
Efficient Low-Pass Dendro-Somatic Coupling in the Apical Dendrite of Layer 5 Pyramidal Neurons in the Anterior Cingulate Cortex

Signal propagation in the dendrites of many neurons, including cortical pyramidal neurons in sensory cortex, is characterized by strong attenuation toward the soma. In contrast, using dual whole-cell recordings from the apical dendrite and soma of layer 5 (L5) pyramidal neurons in the anterior cingulate cortex (ACC) of adult male mice we found good coupling, particularly of slow subthreshold potentials like NMDA spikes or trains of EPSPs from dendrite to soma. Signal propagation in the dendrites of many neurons, including cortical pyramidal neurons in sensory cortex, is characterized by strong attenuation toward the soma. In contrast, using dual whole-cell recordings from the apical dendrite and soma of layer 5 (L5) pyramidal neurons in the anterior cingulate cortex (ACC) of adult male mice we found good coupling, particularly of slow subthreshold potentials like NMDA spikes or trains of EPSPs from dendrite to soma. Only the fastest EPSPs in the ACC were reduced to a similar degree as in primary somatosensory cortex, revealing differential low-pass filtering capabilities. Furthermore, L5 pyramidal neurons in the ACC did not exhibit dendritic Ca2+ spikes as prominently found in the apical dendrite of S1 (somatosensory cortex) pyramidal neurons. Fitting the experimental data to a NEURON model revealed that the specific distribution of Ileak, Iir, Im, and Ih was sufficient to explain the electrotonic dendritic structure causing a leaky distal dendritic compartment with correspondingly low input resistance and a compact perisomatic region, resulting in a decoupling of distal tuft branches from each other while at the same time efficiently connecting them to the soma. Our results give a biophysically plausible explanation of how a class of prefrontal cortical pyramidal neurons achieve efficient integration of subthreshold distal synaptic inputs compared with the same cell type in sensory cortices. SIGNIFICANCE STATEMENT Understanding cortical computation requires the understanding of its fundamental computational subunits. Layer 5 pyramidal neurons are the main output neurons of the cortex, integrating synaptic inputs across different cortical layers. Their elaborate dendritic tree receives, propagates, and transforms synaptic inputs into action potential output. We found good coupling of slow subthreshold potentials like NMDA spikes or trains of EPSPs from the distal apical dendrite to the soma in pyramidal neurons in the ACC, which was significantly better compared with S1. This suggests that frontal pyramidal neurons use a different integration scheme compared with the same cell type in somatosensory cortex, which has important implications for our understanding of information processing across different parts of the neocortex.
Dexmedetomidine inhibits microglial activation through SNHG14/HMGB1 pathway in spinal cord ischemia-reperfusion injury mice

Abstract Objective Microglial activation is an essential pathological mechanism of spinal cord ischemia-reperfusion injury (SCIRI). Previous studies showed dexmedetomidine (DEX) could alleviate SCIRI while the mechanism was not clear. This study aims to investigate the role of DEX in microglial activation and clarify the underlying mechanism. Methods The motion function of mice was quantified using the Basso Mouse Scale for Locomotion. The expression of long non-coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) was determined by qRT-PCR. The expression of high-mobility group box 1 (HMGB1) was measured by western blot. The activation of microglia was evaluated by the expression of ED-1 and the levels of TNF-α and IL-6. The interplay between SNHG14 and HMGB1 was confirmed with RNA pull-down and RIP assay. The stability of HMGB1 was measured by ubiquitination assay and cycloheximide-chase assay. Results DEX inhibited microglial activation and down-regulated SNHG14 expression in SCIRI mice and oxygen and glucose deprivation/reoxygenation (OGD/R)-treated primary microglia. Functionally, SNHG14 overexpression reversed the inhibitory effect of DEX on OGD/R-induced microglial activation. Further investigation confirmed that SNHG14 bound to HMGB1, positively regulated HMGB1 expression by enhancing its stability. In addition, the silence of HMGB1 eliminated the pro-activation impact of SNHG14 overexpression on DEX-treated microglia under the OGD/R condition. Finally, in vivo experiments showed SNHG14 overexpression abrogated the therapeutic effect of DEX on SCIRI mice by up-regulating HMGB1. Conclusion DEX accelerated HMGB1 degradation via down-regulating SNHG14, thus inhibiting microglial activation in SCIRI mice.
The combined effect of mesenchymal stem cells and resveratrol on type 1 diabetic neuropathy

Diabetic neuropathy (DN) is one of the most common diabetic complications that results in an increase in patient discomfort and pain. The present study demonstrated that mesenchymal stem cells (MSCs) or resveratrol (RSV) may improve diabetic hyperglycemia and neuropathy. The aim of the present study was to investigate the combined effect of MSCs and RSV on DN. A total of 100 non-obese diabetic mice were divided into the following six groups: Normal control, MSCs, RSV, MSCs + RSV, insulin and diabetic control groups. Following homologous therapy, the levels of blood glucose and C-peptide, islets, nuclear factor (NF)-κB, nerve growth factor (NGF) and myelin basic protein (MBP), and the sciatic nerve structure in each group were examined and evaluated. Following the administration of therapy, the levels of blood glucose and C-peptide in mice in the MSCs + RSV group were significantly improved when compared with the other diabetic groups, and the dosage of insulin therapy required was the lowest among the six experimental groups (P<0.05). The levels of NGF, MBP and NF-κB in the MSCs + RSV group were significantly improved compared with the MSCs and RSV groups (P<0.05). Furthermore, the diameter of the axon, number of myelinated nerve fibers and the depth of the myelin sheath in the MSCs + RSV group were greatest among the five examined groups (excluding the control). The combination of RSV and MSCs could relieve hyperglycemia and improve DN. This indicated that the combination of RSV and MSCs may be a novel therapeutic method for the treatment of DN.
The issue of fairness in strategic interactions.

The main aim of this doctoral thesis is to examine the issue of fairness in strategic interactions. More specifically, the research here presented investigated, through three main experimental studies and the replication of one of them at the University of Leiden, whether previous “experiences” could affect decisions in strategic games, such as the Ultimatum Game (UG, Guth et al., 1982) and the Dictator Game (DG, Kahneman et al., 1986). Furthermore, it was investigated whether this hypothesized effect was mediated by the emotional reaction elicited by these previous experiences and/or by emotions and beliefs strictly related to the decisions. The theoretical framework, within which the three experimental studies (and the replication of the last one) have been conceived, have been examined and the most important theories about fairness in social decision-making have been presented. Afterwards, the studies will be described. The UG and the DG have been included in a wider framework of interaction between two players and a two-stage paradigm was used. It was investigated only the role of proposer, since the thesis focused on the factors leading people to make fair vs. selfish choices. In conclusion, the theoretical and practical aspects of the results obtained in the four experimental studies have been discussed.
EXPERIMENTAL ANALYSIS OF THE NONLINEAR BEHAVIOUR OF FATIGUED METALLIC SAMPLES

The nonlinear behaviour of intact and fatigued metallic bars flexurally and/or extensionally vibrating has been studied by means of a new experimental procedure for ultrasonic fatigue damage initiation and detection. The procedure is based on the measurement of the vibration velocity of stepped bar samples vibrating at their first resonant mode for different excitation levels. The reverberation of the vibration velocity signal, picked-up by a laser vibrometer, is automatically acquired and analysed by classical FFT methods. The tests have been done with samples of titanium and aluminium alloys. The fatigue of the material is produced by using the driving signal at high excitation levels in the same experimental set-up developed for detection. Two types of experimental studies have been carried out: determination of the fatigue stress at high frequency and comparison between the nonlinear behaviour of intact and fatigued samples. The results show a notable increase of the nonlinear characteristics of the fatigued samples with respect to the original intact samples. In particular, the variation of the third harmonic becomes very relevant. INTRODUCTION The problem of the high frequency (sonic or ultrasonic) fatigue strength of metals has not been very much investigated even if it is an important and useful topic in the aeronautic, aerospatial, and energy industries. In the last years, the use of nonlinear methods for investigating the formation and evolution of microdamage within a material has notably increased (see for example [2, 3]). The interest of using these tools in the analysis and prediction of fatigue has also been shown [4, 5]. We have developed an experimental system to produce and analyze ultrasonic fatigue in metals [1]. In this study we use it to analyze the nonlinear behaviour of the materials before and after fatiguing. We compare the nonlinear elastic behaviour of intact and fatigued samples of titanium alloys commonly used in the aeronautic and aerospatial industries. This paper describes the experimental system as well as the procedure for the dynamic nonlinear characterization of the material. Experimental results are presented and commented. V O L T M E T E R T R A N S D U C E R S a n d w ic h S te p p e d h o rn L A S E R
Treating Children and Adolescents with Posttraumatic Stress Disorder: Moderators of Treatment Response

ABSTRACT Youth exposed to a wide range of potentially traumatic events, such as natural disasters, acts of violence, terrorism, motor vehicle accidents, and life-threatening illnesses, are at risk for developing posttraumatic stress disorder (PTSD) or significant posttraumatic stress symptoms (PTSS). Recent reviews of the existing evidence-base for the treatment of PTSD in children and adolescents identified trauma-focused cognitive behavioral therapy (TF-CBT) and cognitive behavioral therapy (CBT) as well-established treatments. However, studies that evaluated treatment moderators have been scant. Research on treatment moderators is important for guiding clinical decision-making around selecting treatments that might be most effective given the characteristics and circumstances of a particular child or adolescent. Thus, this article provides an updated review of potential moderators evaluated in recent (i.e., past 5 years) meta-analyses and systematic reviews of psychological treatments for PTSD in youth. The moderators examined were in the areas of youth characteristics (age, gender, ethnicity, domicile), parent/caregiver factors (involvement, functioning), trauma type, and treatment factors (dose, individual/group, provider, exposure elements, sudden gains). Some support was identified for age, gender, domicile, parent/caregiver involvement, maternal depressive symptoms, treatment dose, individual/group, and sudden gains as possible treatment moderators, although the strength of the evidence varied and more research is needed to clarify findings. Further study of moderators will be essential to advance the knowledge base in the treatment of PTSD in youth. Video Abstract Read the transcript Watch the video on Vimeo
Microvascular Anatomy and Intrinsic Gene Expression of Menisci From Young Adults

Background: Meniscal vascular supply is an important determinant of its healing potential. It has been reported that only the peripheral 30% of the meniscus is vascularized in cadavers aged 53 to 94 years; however, the vascularity in young patients, in whom meniscal repair is more often performed, is unknown. Purpose: The primary objective was to analyze and measure the microvascular anatomy of the meniscus in adult cadaveric specimens <35 years old. The secondary objective was to assess angiogenic potential by quantifying regional gene expression in a meniscal allograft cohort <45 years old. Study Design: Descriptive laboratory study. Methods: In part 1 of this study, 13 fresh-frozen cadaveric knees (age range, 22-34 years; mean, 28.5 years) underwent popliteal artery India ink injection and tissue clearing using a Spalteholz technique, followed by microvascular vascular measurement. In part 2, mRNA was isolated from 13 meniscal allografts (age range, 17-43 years; mean, 27.2 years), and expression of angiogenic genes, vascular endothelial growth factor (VEGF), and vascular endothelial growth factor receptor 1 (FLT1) was quantified using real-time polymerase chain reaction. Results: The maximal depth of vascular penetration into the periphery of the medial and lateral menisci ranged from 0% to 42% and 0% to 48%, respectively. There was variation in the degree of vascular penetration within the medial meniscus, with the posterior horn having a significantly smaller depth of penetration (median, 8.7%) than that of the anterior horn (median, 17.4%; P < .0001) or midbody (median, 17.5%; P = .0003). There were no differences in angiogenesis gene expression (VEGF/FLT1) based on circumferential or radial meniscal locations. Conclusion: The vascular supply of the medial and lateral menisci in specimens from adults <35 years of age extended farther than what was reported in specimens from older individuals; however, median values remained consistent. Gene expression of the angiogenic marker VEGF was low throughout all regions of uninjured menisci from young adults, which is consistent with reports in older specimens. Clinical Relevance: Improved understanding of meniscal vascular supply in young adults is critical to informing clinical treatment decisions.
Adolescents’ Awareness of and Attitudes Toward Expedited Partner Therapy Provided in the Emergency Department

This survey study found that adolescents were likely to give expedited partner therapy received in the pediatric emergency department to his/her partner. Future effort should incorporate expedited partner therapy into pediatric emergency department workflows. Background Adolescents and young adults account for half of the 20 million new cases of sexually transmitted infections each year. Expedited partner therapy (EPT) has been shown to decrease reinfection rates and is recommended by the Centers for Disease Control and Prevention. We aimed to (1) assess adolescents’ awareness of EPT, (2) assess their likelihood of giving EPT received in the pediatric emergency department (PED) to their partner(s), and (3) identify factors associated with increased likelihood of giving EPT to their partner(s). Methods Adolescents and young adults aged 14 to 22 years seeking care in 2 PEDs participated in a survey. Main outcomes were EPT awareness and likelihood of giving EPT to his/her partner(s). Patients were dichotomized into likely and not likely to provide partner(s) with EPT based on answers to a 5-point Likert scale question. χ2 and t tests were used to analyze the data. Results Three hundred ninety-three participants were included. Only 11% (n = 42) were aware of EPT; however, 80% (n = 316) reported to be likely to give EPT received in the PED to his/her partner(s). Study site, being sexually active, and engaging in high-risk sexual behaviors were associated with an increased likelihood of giving EPT to their partner(s) (P < 0.05). Conclusions Many adolescents are not aware of EPT; however, most were theoretically likely to give EPT received in the PED to his/her partner(s). With increasing rates of sexually transmitted infections and high utilization of the PED for adolescent reproductive health services, efforts to incorporate the use of EPT in PED workflows would be beneficial.
Ultrasound-guided vs conventional arthrocentesis for management of temporomandibular joint disorders: A systematic review and meta-analysis

ABSTRACT Objective This systematic review and meta-analysis aimed to compare outcomes between ultrasound (US)-guided arthrocentesis and conventional arthrocentesis for the management of temporomandibular joint disorders (TMDs). Methods PubMed, Embase, Scopus, BioMed Central, CENTRAL, and Google scholar databases were searched up to April 1 2020 for randomized control trials (RCTs) comparing US-guided and conventional arthrocentesis. Results Four RCTs were included. Pooled analysis did not demonstrate any statistically significant difference in pain or maximal mouth opening (MMO) scores after 1 week and 1 month of follow-up between US-guided and conventional arthrocentesis. Studies also reported data on intra-operative needle relocations and operating time but with conflicting results. Conclusion This study indicates that the use of US during arthrocentesis may not improve postoperative pain and MMO in the short term. Data on intra-operative outcomes are scarce and conflicting for any definitive conclusions. Further high-quality adequately powered RCTs are required to strengthen current evidence.
Milk thistle seed cold press oil attenuates markers of the metabolic syndrome in a mouse model of dietary-induced obesity.

Milk thistle cold press oil (MTO) is an herbal remedy derived from Silybum marianum which contains a low level of silymarin and mixture of polyphenols and flavonoids. The effect of MTO on the cardiovascular and metabolic complications of obesity was studied in mice that were fed a high-fat diet (HFD) for 20 weeks and treated with MTO for the final 8 weeks of the diet. MTO treatment attenuated HFD-induced obesity, fasting hyperglycemia, hypertension, and induced markers of mitochondrial fusion and browning of white adipose. Markers of inflammation were also attenuated in both adipose and the liver of MTO-treated mice. In addition, MTO resulted in the improvement of liver fibrosis. These results demonstrate that MTO has beneficial actions to attenuate dietary obesity-induced weight gain, hyperglycemia, hypertension, inflammation, and suggest that MTO supplementation may prove beneficial to patients exhibiting symptoms of metabolic syndrome. PRACTICAL APPLICATIONS: Natural supplements are increasingly being considered as potential therapies for many chronic cardiovascular and metabolic diseases. Milk thistle cold press oil (MTO) is derived from Silybum marianum which is used as a dietary supplement in different parts of the world. The results of the present study demonstrate that MTO supplementation normalizes several metabolic and cardiovascular complications arising from dietary-induced obesity. MTO supplementation also had anti-inflammatory actions in the adipose as well as the liver. These results suggest that supplementation of MTO into the diet of obese individuals may afford protection against the worsening of cardiovascular and metabolic disease and improve inflammation and liver fibrosis.
Growth and yield of Baby Corn (Zea Mays L.) as influenced by varieties, spacings and dates of sowing

A field experiment was conducted during the rabi season of 2007-08 and 2008-09 on sandy loam soil at Crop Research Farm, Allahabad Agricultural Institute - Deemed University, Allahabad (U.P.) to study the effect of two varieties (VL Baby Corn-1 and HM 4), two spacings (45×25 cm and 60×25 cm) and three sowing dates (1st October, 30th October and 29th November) on performance of baby corn (Zea mays L.). The results indicated that variety HM 4 recorded significantly higher growth, yield contributes and yields viz., plant dry weight (19.07%), crop growth rate (31.85%), days to tasselling (38.64%), days to silking (34.79%) number of cobs/ plant (8.40%), weight of corn with husk (8.49), weight of corn without husk (1.30%), corn yield (8.68%) and fodder yield (21.60%) was found to be higher over VL Baby Corn-1, according pooled data. The maximum length of corn (3.90%), corn yield (32.55%) and fodder yield (26.21%) was found to be higher over 60×25 cm spacing. The baby corn planted on 30th October recorded significantly higher number of cobs/ plant (47.33%), corn yield (35.79%) and fodder yield (20.59%) was found to be higher over sowing on 1st October. Variety HM 4 sown on 30th October at 45×25 cm spacing resulted in maximum gross return, net return and benefit cost ratio.
Role of asymptomatic hyperuricemia in the progression of chronic kidney disease and cardiovascular disease

Previous research has investigated whether hyperuricemia serves as an independent risk factor for cardiovascular and renal diseases. Hyperuricemia is defined as an abnormally high level of uric acid (UA; i.e., serum urate level > 6.8 mg/dL). Hyperuricemia has been considered a complication of chronic kidney disease (CKD). However, it seems to play a pathogenic role in the progression of renal diseases. There has been increasing focus on the link between hyperuricemia and CKD. The results of randomized controlled trials have implied independent associations between hyperuricemia and the progression of cardiovascular and renal morbidities. These associations may be mediated by renin-angiotensin system activation, nitric oxide synthase inhibition, and macrovascular/microvascular disease development. There remains controversy regarding the use of serum UA level as an indirect index of renal vascular disease. This literature review focuses on the role of asymptomatic hyperuricemia in the progression of CKD, as well as the association between hyperuricemia and cardiovascular disease. It also provides a general overview of the physiological metabolism of UA.