Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of a Dopamine-Dependent Limbic–Motor Network in Sensory Motor Processing in Parkinson Disease

Abstract Limbic and motor integration is enabled by a mesial temporal to motor cortex network. Parkinson disease (PD) is characterized by a loss of dorsal striatal dopamine but relative preservation of mesolimbic dopamine early in disease, along with changes to motor action control. Here, we studied 47 patients with PD using the Simon conflict task and [18F]fallypride PET imaging. Additionally, a cohort of 16 patients participated in a single-blinded dextroamphetamine (dAMPH) study. Task performance was evaluated using the diffusion model for conflict tasks, which allows for an assessment of interpretable action control processes. First, a voxel-wise examination disclosed a negative relationship, such that longer non-decision time is associated with reduced D2-like binding potential (BPND) in the bilateral putamen, left globus pallidus, and right insula. Second, an ROI analysis revealed a positive relationship, such that shorter non-decision time is associated with reduced D2-like BPND in the amygdala and ventromedial OFC. The difference in non-decision time between off-dAMPH and on-dAMPH trials was positively associated with D2-like BPND in the globus pallidus. These findings support the idea that dysfunction of the traditional striatal–motor loop underlies action control deficits but also suggest that a compensatory parallel limbic–motor loop regulates motor output.
Molecular mechanisms of TWIST1‐regulated transcription in EMT and cancer metastasis

TWIST1 induces epithelial‐to‐mesenchymal transition (EMT) to drive cancer metastasis. It is yet unclear what determines TWIST1 functions to activate or repress transcription. We found that the TWIST1 N‐terminus antagonizes TWIST1‐regulated gene expression, cancer growth and metastasis. TWIST1 interacts with both the NuRD complex and the NuA4/TIP60 complex (TIP60‐Com) via its N‐terminus. Non‐acetylated TWIST1‐K73/76 selectively interacts with and recruits NuRD to repress epithelial target gene transcription. Diacetylated TWIST1‐acK73/76 binds BRD8, a component of TIP60‐Com that also binds histone H4‐acK5/8, to recruit TIP60‐Com to activate mesenchymal target genes and MYC. Knockdown of BRD8 abolishes TWIST1 and TIP60‐Com interaction and TIP60‐Com recruitment to TWIST1‐activated genes, resulting in decreasing TWIST1‐activated target gene expression and cancer metastasis. Both TWIST1/NuRD and TWIST1/TIP60‐Com complexes are required for TWIST1 to promote EMT, proliferation, and metastasis at full capacity. Therefore, the diacetylation status of TWIST1‐K73/76 dictates whether TWIST1 interacts either with NuRD to repress epithelial genes, or with TIP60‐Com to activate mesenchymal genes and MYC. Since BRD8 is essential for TWIST1‐acK73/76 and TIP60‐Com interaction, targeting BRD8 could be a means to inhibit TWIST1‐activated gene expression.
A preliminary study of minimal left atrial appendage occlusion using Watchman under the guidance of fluoroscopy

Left atrial appendage occlusion (LAAO) has been considered an alternative treatment to prevent embolic stroke in patients with nonvalvular atrial fibrillation (NVAF). However, it carries a risk of general anesthesia or esophageal injury if guided by transesophageal echocardiography (TEE).
Lactose-Functionalized Carbosilane Glycodendrimers Are Highly Potent Multivalent Ligands for Galectin-9 Binding: Increased Glycan Affinity to Galectins Correlates with Aggregation Behavior

Galectins, the glycan binding proteins, and their respective carbohydrate ligands represent a unique fundamental regulatory network modulating a plethora of biological processes. The advances in galectin-targeted therapy must be based on a deep understanding of the mechanism of ligand–protein recognition. Carbosilane dendrimers, the well-defined and finely tunable nanoscaffolds with low toxicity, are promising for multivalent carbohydrate ligand presentation to target galectin receptors. The study discloses a synthetic method for two types of lactose-functionalized carbosilane glycodendrimers (Lac-CS-DDMs). Furthermore, we report their outstanding, dendritic effect-driven affinity to tandem-type galectins, especially Gal-9. In the enzyme-linked immunosorbent assay, the affinity of the third-generation multivalent dendritic ligand bearing 32 lactose units to Gal-9 reached nanomolar values (IC50 = 970 nM), being a 1400-fold more effective inhibitor than monovalent lactose for this protein. This demonstrates a game-changing impact of multivalent presentation on the inhibitory effect of a ligand as simple as lactose. Moreover, using DLS hydrodynamic diameter measurements, we correlated the increased affinity of the glycodendrimer ligands to Gal-3 and Gal-8 but especially to Gal-9 with the formation of relatively uniform and stable galectin/Lac-CS-DDM aggregates.
Older Veterans’ Experiences of a Multicomponent Telehealth Program: Qualitative Program Evaluation Study

Background There are 8.8 million American veterans aged >65 years. Older veterans often have multiple health conditions that increase their risk of social isolation and loneliness, disability, adverse health events (eg, hospitalization and death), mental illness, and heavy health care use. This population also exhibits low levels of physical function and daily physical activity, which are factors that can negatively influence health. Importantly, these are modifiable risk factors that are amenable to physical therapy intervention. We used a working model based on the dynamic biopsychosocial framework and social cognitive theory to conceptualize the multifactorial needs of older veterans with multiple health conditions and develop a novel, 4-component telehealth program to address their complex needs. Objective This study aims to describe veterans’ experiences of a multicomponent telehealth program and identify opportunities for quality and process improvement. We conducted qualitative interviews with telehealth program participants to collect their feedback on this novel program; explore their experience of program components; and document perceived outcomes and the impact on their daily life, relationships, and quality of life. Methods As part of a multimethod program evaluation, semistructured interviews were conducted with key informants who completed ≥8 weeks of the 12-week multicomponent telehealth program for veterans aged ≥50 years with at least 3 medical comorbidities. Interviews were audio recorded and transcribed. Data were analyzed by a team of 2 coders using a directed content analysis approach and Dedoose software was used to assist with data analysis. Results Of the 21 individuals enrolled in the program, 15 (71%) met the inclusion criteria for interviews. All 15 individuals completed 1-hour interviews. A total of 6 main conceptual domains were identified: technology, social networks, therapeutic relationship, patient attributes, access, and feasibility. Themes associated with each domain detail participant experiences of the telehealth program. Key informants also provided feedback related to different components of the program, leading to adaptations for the biobehavioral intervention, group sessions (transition from individual to group sessions and group session dynamics), and technology supports. Conclusions Findings from this program evaluation identified quality and process improvements, which were made before rigorously testing the intervention in a larger population through a randomized controlled trial. The findings may inform adaptations of similar programs in different contexts. Further research is needed to develop a deeper understanding of how program components influence social health and longer-term behavior change.
Developing flexible models for genetic evaluations in smallholder crossbred dairy farms

The productivity of smallholder dairy farms is very low in developing countries. Important genetic gains could be realized using genomic selection, but genetic evaluations need to be tailored for lack of pedigree information and very small farm sizes. To accommodate this situation, we propose a flexible Bayesian model for the genetic evaluation of milk yield, which allows us to simultaneously account for nongenetic random effects for farms and varying SNP variance (BayesR model). First, we used simulations based on real genotype data from Indian crossbred dairy cattle to demonstrate that the proposed model can separate the true genetic and nongenetic parameters even for small farm sizes (2 cows on average) although with high standard errors in scenarios with low heritability. The accuracy of genomic genetic evaluation increased until farm size was approximately 5. We then applied the model to real data from 4,655 crossbred cows with 106,109 monthly test day milk records and 689,750 autosomal SNPs. We estimated a heritability of 0.16 (0.04) for milk yield and using cross-validation, a genomic estimated breeding value (GEBV) accuracy of 0.45 and bias (regression of phenotype on GEBV) of 1.04 (0.26). Estimated genetic parameters were very similar using BayesR, BayesC, and genomic BLUP approaches. Candidate genes near the top variants, IMMP2L and ARHGEF2, have been previously associated with milk protein composition, mastitis resistance, and milk cholesterol content. The estimated heritability and GEBV accuracy for milk yield are much lower than those from intensive or pasture-based systems in many countries. Further increases in the number of phenotyped and genotyped animals in farms with at least 2 cows (preferably 3–5, to allow for dropout of cows) are needed to improve the estimation of genetic effects in these smallholder dairy farms.
Early diagnosis of necrotizing fasciitis: Imaging techniques and their combined application

Abstract Necrotizing fasciitis is a clinical, surgical emergency characterized by an insidious onset, rapid progression, and a high mortality rate. The disease's mortality rate has remained high for many years, mainly because of its atypical clinical presentation, which prevents many cases from being diagnosed early and accurately, resulting in patients who may die from uncontrollable septic shock and multi‐organ failure. But unfortunately, no diagnostic indicator can provide a certain early diagnosis of NF, and clinical judgement of NF is still based on the results of various ancillary tests combined with the patient's medical history, clinical manifestations, and the physician's experience. This review provides a brief overview of the epidemiological features of NF and then discusses the most important laboratory indicators and scoring systems currently employed to diagnose NF. Finally, the latest progress of several imaging techniques in the early diagnosis of NF and their combined application with other diagnostic indices are highlighted. We point out promising research directions based on an objective evaluation of the advantages and shortcomings of different methods, which provide a basis for further improving the early diagnosis of NF.
Consensus molecular subtype transition during progression of colorectal cancer

The consensus molecular subtype (CMS) classification divides colorectal cancer (CRC) into four distinct subtypes based on RNA expression profiles. The biological differences between CMSs are already present in CRC precursor lesions, but not all CMSs pose the same risk of malignant transformation. To fully understand the path to malignant transformation and to determine whether CMS is a fixed entity during progression, genomic and transcriptomic data from two regions of the same CRC lesion were compared: the precursor region and the carcinoma region. In total, 24 patients who underwent endoscopic removal of T1–2 CRC were included. Regions were subtyped for CMS and DNA mutation analysis was performed. Additionally, a set of 85 benign adenomas was CMS‐subtyped. This analysis revealed that almost all benign adenomas were classified as CMS3 (91.8%). In contrast, CMS2 was the most prevalent subtype in precursor regions (66.7%), followed by CMS3 (29.2%). CMS4 was absent in precursor lesions and originated at the carcinoma stage. Importantly, CMS switching occurred in a substantial number of cases and almost all (six out of seven) CMS3 precursor regions showed a shift to a different subtype in the carcinoma part of the lesion, which in four cases was classified as CMS4. In conclusion, our data indicate that CMS3 is related to a more indolent type of precursor lesion that less likely progresses to CRC and when this occurs, it is often associated with a subtype change that includes the more aggressive mesenchymal CMS4. In contrast, an acquired CMS2 signature appeared to be rather fixed during early CRC development. Combined, our data show that subtype changes occur during progression and that CMS3 switching is related to changes in the genomic background through acquisition of a novel driver mutation (TP53) or selective expansion of a clone, but also occurred independently of such genetic changes. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
The Control of Grain-Scale Mechanics on Channel form, Landscape Dynamics, and Climatic Perturbations in Gravel-Bedded Rivers

Landscapes evolve over millions of years, through the complex interplay of climate and tectonics. Mountains in particular represent a staggering range of spatial and temporal scales, challenging our ability to understand how the landscape is sculpted. Mountains do not simply disappear by bulk denudation. The key process of river incision results from the entrainment, displacement, and collision of coarse particles with the bed; a phenomenon known as bed load transport. This dissertation seeks to elucidate how bed load transport in natural rivers is driven by floods, to provide a mechanistic connection between climate and landscape evolution. Field surveys of coarse particle displacement and channel geometry are combined with hydrological time series, to study the interaction between floods and bed load dynamics, and their implications for channel form. Results from tagged cobbles demonstrate that mean particle displacement is proportional to applied fluid momentum in excess of the threshold of motion, while dispersion of tracers is superdiffusive due to the burial and excavation of cobbles. These field surveys reveal that particle motion remains in a state of partial transport for a diverse population of flows, and that particle sorting and transport distances closely match theory developed from small-scale laboratory experiments. Analysis of hydrological time series shows that the threshold of particle motion truncates the distribution of applied stress, resulting in thin-tailed distributions of forcing for flows above the threshold of motion. This analysis further shows that, because a coarse-grained river adjusts its geometry so that the flow at the banks is at the threshold of motion, the probability of experiencing larger stresses diminishes exponentially. Field surveys of channel geometry and particle size reveal that the geomorphological impacts of urbanization are reduced for coarse-grained channels adjusted to frequent sediment transport events. Taken together, these observations indicate that the threshold of particle motion represents a first-order control on the influence of climate on river dynamics, and the landscapes through which they flow. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Earth & Environmental Science First Advisor Douglas J. Jerolmack
Viabilité des semences de quelques espèces pastorales steppiques tunisiennes en rapport avec les conditions de leur conservation

Les performances germinatives des semences de quatorze especes steppiques, susceptibles d’etre reensemencees lors d’essais de rehabilitation des parcours degrades de la Tunisie aride, ont fait l’objet d’un suivi, apres conservation sous differentes conditions (conditions ambiantes de laboratoire, sechage et conservation hermetique dans les conditions ambiantes et a faible temperature : 5°C). Parmi les especes etudiees il a ete montre que, dans les conditions ambiantes de conservation, les semences de Salsola vermiculata sont celles qui perdent le plus rapidement leur faculte germinative soit quelques mois apres la dissemination. Chez Stipagrostis ciliata et Artemisia herba-alba un certain pourcentage de graines âgees d’une annee peuvent encore germer. La viabilite des semences d’autres especes peut meme depasser les trois ans. La conservation hermetique, apres sechage des semences, aussi bien dans les conditions ambiantes qu’a faible temperature permet de prolonger la viabilite des semences de l’ensemble des especes etudiees. Dans l’intervalle de temps correspondant a la duree de l’experimentation (quatre annees), l’avantage de la conservation a faible temperature est, cependant, plus evident chez S. vermiculata. A la lumiere de ces resultats et compte tenu du cout de conditionnement des semences on peut dire qu’une conservation hermetique apres sechage des semences semble utile pour la plupart des especes, specialement pour A. herba-alba et pour les quatre poaceae etudiees. La conservation a faible temperature apres sechage n’est imperative et envisageable que pour les semences de S. vermiculata ou pour une conservation a long terme des ressources phytogenetiques.
Cavernous malformations of the nervous system

This publication is in copyright. Subject to statutory exception and to the provisions of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press. A catalogue record for this publication is available from the British Library Library of Congress Cataloging in Publication data Cavernous malformations of the nervous system / edited by Daniele Rigamonti. Cambridge University Press has no responsibility for the persistence or accuracy of URLs for external or third-party internet websites referred to in this publication, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate. Every effort has been made in preparing this book to provide accurate and up-to-date information which is in accord with accepted standards and practice at the time of publication. Although case histories are drawn from actual cases, every effort has been made to disguise the identities of the individuals involved. Nevertheless, the authors, editors and publishers can make no warranties that the information contained herein is totally free from error, not least because clinical standards are constantly changing through research and regulation. The authors, editors and publishers therefore disclaim all liability for direct or consequential damages resulting from the use of material contained in this book. Readers are strongly advised to pay careful attention to information provided by the manufacturer of any drugs or equipment that they plan to use. Cambridge University Press 978-0-521-76427-8-Cavernous Malformations of the Nervous System Edited by Daniele Rigamonti Frontmatter More information I dedicate this book to my wife and children, to the memory of my father, who exemplified for me how a physician should practice, and to Bunny and Charles Salisbury who supported my research over all these years.
Viscoelasticity in trapezius myofascial pain syndrome: quantitative assessment using Real-Time Shear-Wave Elastography

Abstract Objective To investigate the differences in the viscoelastic properties between normal trapezius muscles and those in patients with trapezius myofascial pain syndrome (MPS) using real-time shear-wave elastography (SWE). Materials and Methods This study included 31 patients with trapezius MPS and 31 volunteers. Sixty-one trapezius muscles (41 and 20 on the affected and non-affected side, respectively) of patients with MPS and 62 normal trapezius muscles in volunteers were assessed. Conventional ultrasonic parameters, including skeletal muscle thickness, resistance index (RI), and mean shear wave velocity (SWVmean) of trapezius muscles, were obtained in the seated position with the shoulders and neck relaxed. The daily neck leaning time (unit:hours) of all participants was obtained using a questionnaire. Results Ultrasound showed no statistically significant differences in thickness or RI of the trapezius muscles of the affected and non-affected sides in MPS patients versus normal trapezius muscles (p = 0.976 and 0.106, respectively). In contrast, the SWVmean of trapezius muscles in patients with MPS was significantly higher than that of normal trapezius muscles in both the affected and non-affected sides (4.41 ± 1.02 m/s vs. 3.35 ± 0.79 m/s, p < 0.001; 4.05 ± 0.63 m/s vs. 3.35 ± 0.79 m/s, p = 0.002). There was no significant difference between the SWVmean of the trapezius muscles on the affected and non-affected sides in patients with MPS (4.41 ± 1.02 m/s vs. 4.05 ± 0.63 m/s, p = 0.225). Correlation analysis showed that daily neck forward time was positively correlated with the SWVmean of the trapezius muscles on the affected and non-affected sides in patients with MPS (r = 0.635, p < 0.001; r = 0.576, p = 0.008). Conclusion SWE can quantitatively evaluate stiffness of trapezius muscles in patients with trapezius MPS. The stiffness of both affected and non-affected trapezius muscles increased in patients with trapezius MPS, and the degree of increase positively correlated with the time of cervical forward leaning.
Un segment de crôute continentale d'âge archéen ancien (3,4 milliards d'années) : le massif de Sete Voltas (Bahia, Brésil)

Le massif de Sete Voltas (craton de Sao Francisco, Bresil) contient des reliques de gneiss gris anciens (âge Rb-Sr=3,42±0,09 Ga et âge monozircon =3,394±0,005 Ga) en enclave dans un complexe plutonique date entre 3,14±0,09 Ga (gneiss gris recents)et 3,17±0,16 Ga (granodiorites porphyroides); il s'agit des plus anciennes roches connues a ce jour au Bresil
Role of Contrast‐Enhanced Ultrasound in Evaluation of Cystic Renal Mass

Contrast‐enhanced ultrasound (CEUS) allows excellent delineation of perfusion in septa and nodules without exposure to ionizing radiation or nephrotoxic contrast media. The aim of our study was to evaluate the role of CEUS for the assessment of cystic renal masses and compare its diagnostic performance with that of CECT.
Put Into Perspective for the Practicing Clinician 987 Coronary Heart Disease Mortality Declines in the United States From 1979 Through 2011 : Evidence for Stagnation in Young Adults , Especially Women

This article reports for the first time national trends in coronary heart disease (CHD) mortality by sex and age for the past 30 years, from 1979 to 2011. The analysis reveals significant heterogeneity in CHD mortality rates over time by sex and age. Older adults, especially men ≥55 years of age and women ≥65 years of age, have shown robust CHD mortality reductions over the past 2 decades with an acceleration over the past decade. In contrast, young adults <55 years old have shown sluggish improvements in the same time period; the gains in CHD mortality reduction have been especially weak for young women. These data suggest that attention should be given to the young population, especially women, whose cardiovascular risk profile may have worsened disproportionally in recent decades, which may potentially explain their less favorable trends in CHD mortality reduction. See p 997.