bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laser interstitial thermal therapy of lung lesions near large vessels: a numerical study
Authors: Effat Andrew , Bernards Nicholas , Gregor Alexander , Young Edmond W K , Yasufuku Kazuhiro , Weersink Robert A 
Published: March 2023

Abstract

Objective. Laser interstitial thermal therapy (LITT) is an evolving hyperthermia-based technology that may offer a minimally invasive alternative to inoperable lung cancer. LITT of perivascular targets is challenged by higher risk of disease recurrence due to vascular heat sinks, as well as risk of damage to these vascular structures. The objective of this work is to examine the impact of multiple vessel parameters on the efficacy of the treatment and the integrity of the vessel wall in perivascular LITT. Approach. A finite element model is used to examine the role of vessel proximity, flow rate, and wall thickness on the outcome of the treatment. Main result. The simulated work indicates that vessel proximity is the major factor in driving the magnitude of the heat sink effect. Vessels situated near the target volume may act as a protective measure for reducing healthy tissue damage. Vessels with thicker walls are more at risk of damage during treatment. Interventions to reduce the flow rate may reduce the vessel’s heat sink effect but may also result in increased risk of vascular wall damage. Lastly, even at reduced blood flow rates, the volume of blood reaching the threshold of irreversible damage (>43 °C) is negligible compared to the volume of blood flow throughout the treatment duration. Significance. This investigative simulation yields results that may help guide clinicians on treatment planning near large vessels.
Significance of the Percentage of Gleason Pattern 4 at Prostate Biopsy in Predicting Adverse Pathology on Radical Prostatectomy: Application in Active Surveillance
Authors: Ordner Jeffrey , Flaifel Abdallah , Serrano Antonio , Graziano Rebecca , Melamed Jonathan , Deng Fang-Ming 
Published: March 2023

Abstract

Objectives
To determine the prognostic significance of the maximum allowable percentage of Gleason pattern 4 (GP4) at prostate biopsy compared with adverse pathology observed at radical prostatectomy (RP) to expand active surveillance eligibility among a cohort with intermediate risk of prostate cancer.

Methods
A retrospective study of patients with grade group (GG) 1 or 2 prostate cancer on prostate biopsy with subsequent RP was performed at our institution. A Fisher exact test was used to understand the relationship among GP4 subgroups (0%, ≤5%, 6%-10%, and 11%-49%) assigned at biopsy and adverse pathologic findings at RP. Additional analyses comparing the GP4 ≤5% cohort’s prebiopsy prostate-specific antigen (PSA) level and GP4 length with adverse pathology at RP were also performed.

Results
No statistically significant difference in adverse pathology at RP was observed between the active surveillance–eligible control (GP4 0%) and the GP4 ≤5% subgroup. In total, 68.9% of the GP4 ≤5% cohort showed favorable pathologic outcomes. A separate analysis of the GP4 ≤5% subgroup revealed that neither prebiopsy serum PSA levels nor GP4 length showed statistical correlation with adverse pathology at RP.

Conclusions
Active surveillance may be a reasonable option for management of patients in the GP4 ≤5% group until long-term follow-up data become available.
A Per-Protocol Analysis Using Inverse-Probability-of-Censoring Weights in a Randomized Trial of Initial Protease Inhibitor Versus Nonnucleoside Reverse Transcriptase Inhibitor Regimens in Children
Authors: Yin Dwight E , Cole Stephen R , Ludema Christina , Brookhart M Alan , Golin Carol E , Miller William C , McKinney Ross E 
Published: March 2023

Abstract
Protocol adherence may influence measured treatment effectiveness in randomized controlled trials. Using data from a multicenter trial (Europe and the Americas, 2002–2009) of children with human immunodeficiency virus type 1 who had been randomized to receive initial protease inhibitor (PI) versus nonnucleoside reverse transcriptase inhibitor (NNRTI) antiretroviral therapy regimens, we generated time-to-event intention-to-treat (ITT) estimates of treatment effectiveness, applied inverse-probability-of-censoring weights to generate per-protocol efficacy estimates, and compared shifts from ITT to per-protocol estimates across and within treatment arms. In ITT analyses, 263 participants experienced 4-year treatment failure probabilities of 41.3% for PIs and 39.5% for NNRTIs (risk difference = 1.8% (95% confidence interval (CI): −10.1, 13.7); hazard ratio = 1.09 (95% CI: 0.74, 1.60)). In per-protocol analyses, failure probabilities were 35.6% for PIs and 29.2% for NNRTIs (risk difference = 6.4% (95% CI: −6.7, 19.4); hazard ratio = 1.30 (95% CI: 0.80, 2.12)). Within-arm shifts in failure probabilities from ITT to per-protocol analyses were 5.7% for PIs and 10.3% for NNRTIs. Protocol nonadherence was nondifferential across arms, suggesting that possibly better NNRTI efficacy may have been masked by differences in within-arm shifts deriving from differential regimen forgiveness, residual confounding, or chance. A per-protocol approach using inverse-probability-of-censoring weights facilitated evaluation of relationships among adherence, efficacy, and forgiveness applicable to pediatric oral antiretroviral regimens.
Protein phosphorylation database and prediction tools
Authors: Zhao Ming-Xiao , Chen Qiang , Li Fulai , Fu Songsen , Huang Biling , Zhao Yufen 
Published: March 2023

AbstractProtein phosphorylation, one of the main protein post-translational modifications, is required for regulating various life activities. Kinases and phosphatases that regulate protein phosphorylation in humans have been targeted to treat various diseases, particularly cancer. High-throughput experimental methods to discover protein phosphosites are laborious and time-consuming. The burgeoning databases and predictors provide essential infrastructure to the research community. To date, &gt;60 publicly available phosphorylation databases and predictors each have been developed. In this review, we have comprehensively summarized the status and applicability of major online phosphorylation databases and predictors, thereby helping researchers rapidly select tools that are most suitable for their projects. Moreover, the organizational strategies and limitations of these databases and predictors have been highlighted, which may facilitate the development of better protein phosphorylation predictors in silico.
Mecp2deletion results in profound alterations of developmental and adult functional connectivity
Authors: Rahn Rachel M , Yen Allen , Chen Siyu , Gaines Seana H , Bice Annie R , Brier Lindsey M , Swift Raylynn G , Lee LeiLani , Maloney Susan E , Culver Joseph P , Dougherty Joseph D 
Published: March 2023

AbstractAs a regressive neurodevelopmental disorder with a well-established genetic cause, Rett syndrome and its Mecp2 loss-of-function mouse model provide an excellent opportunity to define potentially translatable functional signatures of disease progression, as well as offer insight into the role of Mecp2 in functional circuit development. Thus, we applied widefield optical fluorescence imaging to assess mesoscale calcium functional connectivity (FC) in the Mecp2 cortex both at postnatal day (P)35 in development and during the disease-related decline. We found that FC between numerous cortical regions was disrupted in Mecp2 mutant males both in juvenile development and early adulthood. Female Mecp2 mice displayed an increase in homotopic contralateral FC in the motor cortex at P35 but not in adulthood, where instead more posterior parietal regions were implicated. An increase in the amplitude of connection strength, both with more positive correlations and more negative anticorrelations, was observed across the male cortex in numerous functional regions. Widespread rescue of MeCP2 protein in GABAergic neurons rescued none of these functional deficits, nor, surprisingly, the expected male lifespan. Altogether, the female results identify early signs of disease progression, while the results in males indicate MeCP2 protein is required for typical FC in the brain.
Exosomal miR-103a-3p from Crohn’s Creeping Fat-Derived Adipose-Derived Stem Cells Contributes to Intestinal Fibrosis by Targeting TGFBR3 and Activating Fibroblasts
Authors: Qian Wenwei , Xu Yihan , Wen Weiwei , Huang Liangyu , Guo Zhen , Zhu Weiming , Li Yi 
Published: March 2023

Abstract

Background and Aims
Mesenteric adipose tissue hypertrophy is a hallmark of Crohn’s disease [CD], and creeping fat [CF] is unique to CD. Adipose-derived stem cells [ASCs] from inflammatory tissue exhibited altered biological functions. The role of ASCs isolated from CF in intestinal fibrosis and the potential mechanism remain unclear.

Methods
ASCs were isolated from CF [CF-ASCs] and disease-unaffected mesenteric adipose tissue [Ctrl-ASCs] of patients with CD. A series of in vitro and in vivo experiments were conducted to study the effects of exosomes from CF-ASCs [CF-Exos] on intestinal fibrosis and fibroblast activation. A micro-RNA microarray analysis was performed. Western blot, luciferase assay and immunofluorescence were performed to further detect the underlying mechanisms.

Results
The results indicated that CF-Exos promoted intestinal fibrosis by activating fibroblasts in a dose-dependent manner. They continuously promoted progression of intestinal fibrosis even after dextran sulphate sodium withdrawal. Further analysis showed that exosomal miR-103a-3p was enriched in CF-Exos and participated in exosome-mediated fibroblast activation. TGFBR3 was identified as a target gene of miR-103a-3p. Mechanistically, CF-ASCs released exosomal miR-103a-3p and promoted fibroblast activation by targeting TGFBR3 and promoting Smad2/3 phosphorylation. We also found that the expression of miR-103a-3p in diseased intestine was positively associated with the degree of CF and fibrosis score.

Conclusion
Our findings show that exosomal miR-103a-3p from CF-ASCs promotes intestinal fibrosis by activating fibroblasts via TGFBR3 targeting, suggesting that CF-ASCs are potential therapeutic targets for intestinal fibrosis in CD.
Gene expression profiling of subcutaneous adipose tissue reveals new biomarkers in acromegaly
Authors: Falch Camilla M , Arlien-Søborg Mai Christiansen , Dal Jakob , Sundaram Arvind Y M , Michelsen Annika E , Ueland Thor , Olsen Linn Guro , Heck Ansgar , Bollerslev Jens , Jørgensen Jens Otto L , Olarescu Nicoleta C 
Published: March 2023

AbstractContextActive acromegaly is characterized by lipolysis-induced insulin resistance, which suggests adipose tissue (AT) as a primary driver of metabolic aberrations.ObjectiveTo study the gene expression landscape in AT in patients with acromegaly before and after disease control in order to understand the changes and to identify disease-specific biomarkers.MethodsRNA sequencing was performed on paired subcutaneous adipose tissue (SAT) biopsies from six patients with acromegaly at time of diagnosis and after curative surgery. Clustering and pathway analyses were performed in order to identify disease activity-dependent genes. In a larger patient cohort (n = 23), the corresponding proteins were measured in serum by immunoassay. Correlations between growth hormone (GH), insulin-like growth factor I (IGF-I), visceral AT (VAT), SAT, total AT, and serum proteins were analyzed.Results743 genes were significantly differentially expressed (P-adjusted &lt; .05) in SAT before and after disease control. The patients clustered according to disease activity. Pathways related to inflammation, cell adhesion and extracellular matrix, GH and insulin signaling, and fatty acid oxidation were differentially expressed.Serum levels of HTRA1, METRNL, S100A8/A9, and PDGFD significantly increased after disease control (P &lt; .05). VAT correlated with HTRA1 (R = 0.73) and S100A8/A9 (R = 0.55) (P &lt; .05 for both).ConclusionAT in active acromegaly is associated with a gene expression profile of fibrosis and inflammation, which may corroborate the hyper-metabolic state and provide a means for identifying novel biomarkers.
Determining cardiovascular risk in patients with unattributed chest pain in UK primary care: an electronic health record study
Authors: Jordan Kelvin P , Rathod-Mistry Trishna , van der Windt Danielle A , Bailey James , Chen Ying , Clarson Lorna , Denaxas Spiros , Hayward Richard A , Hemingway Harry , Kyriacou Theocharis , Mamas Mamas A 
Published: March 2023

Abstract

Aims
Most adults presenting in primary care with chest pain symptoms will not receive a diagnosis (‘unattributed’ chest pain) but are at increased risk of cardiovascular events. To assess within patients with unattributed chest pain, risk factors for cardiovascular events and whether those at greatest risk of cardiovascular disease can be ascertained by an existing general population risk prediction model or by development of a new model.

Methods and results
The study used UK primary care electronic health records from the Clinical Practice Research Datalink linked to admitted hospitalizations. Study population was patients aged 18 plus with recorded unattributed chest pain 2002–2018. Cardiovascular risk prediction models were developed with external validation and comparison of performance to QRISK3, a general population risk prediction model. There were 374 917 patients with unattributed chest pain in the development data set. The strongest risk factors for cardiovascular disease included diabetes, atrial fibrillation, and hypertension. Risk was increased in males, patients of Asian ethnicity, those in more deprived areas, obese patients, and smokers. The final developed model had good predictive performance (external validation c-statistic 0.81, calibration slope 1.02). A model using a subset of key risk factors for cardiovascular disease gave nearly identical performance. QRISK3 underestimated cardiovascular risk.

Conclusion
Patients presenting with unattributed chest pain are at increased risk of cardiovascular events. It is feasible to accurately estimate individual risk using routinely recorded information in the primary care record, focusing on a small number of risk factors. Patients at highest risk could be targeted for preventative measures.
Risk factor variability and cardiovascular risk among patients with diabetes: a nationwide observational study
Authors: Ceriello Antonio , Lucisano Giuseppe , Prattichizzo Francesco , La Grotta Rosalba , Franzén Stefan , Gudbjörnsdottir Soffia , Eliasson Björn , Nicolucci Antonio 
Published: March 2023

AbstractAimsCardiovascular risk factor control fluctuates, tends to change over time, and is potentially impacted by multifactorial interactions. Currently, the presence of risk factors, rather than their variability or interplay with one another, is taken into account to define the population at risk. The association between variability of risk factors and cardiovascular morbidity and mortality risk among patients with Type 2 diabetes mellitus (T2DM) remains debatable.Methods and resultsUsing registry-derived data, we identified 29 471 people with T2DM, without cardiovascular disease (CVD) at baseline, and with at least five measurements of risk factors. Variability for each variable was expressed as quartiles of the standard deviation during 3 years (exposure). The incidence of myocardial infarction, stroke, and all-cause mortality was assessed during 4.80 (2.40–6.70) years following the exposure phase. The association between the measures of variability and the risk of developing the outcome was investigated through multivariable Cox proportional-hazards regression analysis with stepwise variable selection. Then, the recursive partitioning and amalgamation (RECPAM) algorithm was used to explore the interaction among the variability of risk factors associated with the outcome. An association between the variability of HbA1c, body weight, systolic blood pressure, and total cholesterol with the outcome considered was found. Among the six classes of risk identified by RECPAM, patients with a high variability of both body weight and blood pressure had the highest risk [Class 6, hazard ratio (HR) = 1.81; 95% confidence interval (CI) 1.61–2.05] compared with patients with low variability of both body weight and total cholesterol (Class 1, reference), despite a progressive reduction in the mean level of risk factors during successive visits. Individuals with high weight variability but low–moderate systolic blood pressure variability (Class 5, HR = 1.57; 95% CI 1.28–1.68), patients with moderate/high weight variability associated with high/very high HbA1c variability (Class 4, HR = 1.33; 95% CI 1.20–1.49), subjects with moderate/high weight variability and with low/moderate HbA1c variability (Class 3, HR = 1.12; 95% CI 1.00–1.25), as well as those with low weight variability associated with high/very high total cholesterol variability (Class 2, HR = 1.14; 95% CI 1.00–1.30) also showed a significant increase in the risk of an event.ConclusionCombined high variability of two risk factors, particularly body weight and blood pressure, is associated with cardiovascular risk among patients with T2DM. These findings highlight the importance of continuous balancing of multiple risk factors.
All Beginnings Are Difficult: The Guiding Principles on Extreme Poverty and Human Rights a Decade After Their Adoption
Authors: Ploszka Adam 
Published: March 2023

Abstract
In September 2022, 10 years had passed since the Guiding Principles on Extreme Poverty and Human Rights were adopted by the Human Rights Council. The Guiding Principles, as a soft law human rights instrument, were designed to be a useful tool for states in the formulation and implementation of poverty reduction and eradication policies. In this piece, I examine to what extent this objective has been met. Based on empirical research involving states’ representatives and civil society organizations, and analysis of the documents produced by United Nations bodies that played a key role in developing a human rights-based approach to poverty, I argue that this objective has been met only to a limited extent.
An adaptive time stepping scheme for rate-independent systems with nonconvex energy
Authors: Andreia Merlin , Meyer Christian 
Published: March 2023

Abstract
We investigate a local incremental stationary scheme for the numerical solution of rate-independent systems. Such systems are characterized by a (possibly) nonconvex energy and a dissipation potential, which is positively homogeneous of degree one. Due to the nonconvexity of the energy, the system does in general not admit a time-continuous solution. In order to resolve these potential discontinuities, the algorithm produces a sequence of state variables and physical time points as functions of a curve parameter. The main novelty of our approach in comparison to existing methods is an adaptive choice of the step size for the update of the curve parameter, depending on a prescribed tolerance for the residua in the energy-dissipation balance, and in a complementarity relation concerning the so-called local stability condition. It is proven that, for tolerance tending to zero, the piecewise affine approximations generated by the algorithm converge (weakly) to a so-called parametrized balanced viscosity solution. Numerical experiments illustrate the theoretical findings, and show that an adaptive choice of the step size indeed pays off as they lead to a significant increase of the step size during sticking and in viscous jumps.
Evaluation of growth, meat quality, and sensory characteristics of wool, hair, and composite lambs
Authors: Heimbuch Mikayla L , Van Buren Jessie B , Epperson Brooklyn S , Jepsen Sierra M , Oliver Kayleen F , Nasados James A , Vinci Dino A , Larson Mallery , Konetchy Denise E , Price William J , Vierck Kelly R , Legako Jerrad F , Loomas Kaitlyn , Insausti Kizkitza , Bass Phillip D , Colle Michael J 
Published: March 2023

AbstractThe objectives of this study were to evaluate the growth rates, carcass quality, shelf-life, tenderness, sensory characteristics, volatile compounds, and fatty acid composition of wool, hair, and composite (wool × hair) lambs. Twenty-one wether lambs [wool (Suffolk × Polypay/Targhee; n = 7), hair (Dorper × Dorper; n = 7), and composite (Dorper × Polypay/Targhee; n = 7)] were fed from weaning to finishing at the University of Idaho Sheep Center and subsequently harvested under United States Department of Agriculture inspection at the University of Idaho Meat Lab. At 48 h postmortem, carcass measurements were taken to determine the percent boneless closely trimmed retail cuts, yield grade, and quality grade. Loins were fabricated from each carcass and wet-aged at 0°C until 10-d postmortem. Following aging, 2.54-cm bone-in loin chops were cut and randomly assigned to 4 d of retail display, Warner–Bratzler Shear Force (WBSF), or sensory analyses. Thiobarbituric acid reactive substances were analyzed on days 0 and 4 of retail display while subjective and objective color measurements were observed once daily. Samples (24 g) were also collected for volatile compound and fatty acid analysis. A mixed model analysis of variance was used to assess breed differences. Discernable effects were considered at P &lt; 0.05. Wool lambs had heavier hot carcass weights (P &lt; 0.001), larger rib-eye area (P = 0.015), and higher dressing percent (P &lt; 0.001) than the other breeds. There was an interaction observed between breed and days of retail display for browning (P = 0.006). On day 1 chops from the composite breed had more browning than chops from the wool breed. No differences were observed between groups for lean muscle L* values (P = 0.432), a* values (P = 0.757), and b* values (P = 0.615). Differences were not observed in lipid oxidation (P = 0.159), WBSF (P = 0.540), or consumer acceptability (P = 0.295). There were differences found for 7 of the 45 fatty acids detected and in 3 of the 67 volatile compounds detected. In conclusion, wool lambs were heavier and had a greater carcass yield than the hair lamb carcasses. Regardless of breed, consumers did not detect sensory traits that would impact their eating experience.