Mineral Stress Drives Loss of Heterochromatin: An Early Harbinger of Vascular Inflammaging and Calcification.

Background: Vascular calcification is a detrimental aging pathology markedly accelerated in patients with chronic kidney disease. Prelamin A is a biomarker of vascular smooth muscle cell aging that accelerates calcification however the mechanisms remain undefined.

Methods: Vascular smooth muscle cells were transduced with prelamin A using an adenoviral vector and epigenetic modifications were monitored using immunofluorescence and targeted polymerase chain reaction array.

FFR-Negative Nonculprit High-Risk Plaques and Clinical Outcomes in High-Risk Populations: An Individual Patient-Data Pooled Analysis From COMBINE (OCT-FFR) and PECTUS-obs.

Background: Despite fractional flow reserve (FFR)-guided deferral of revascularization, recurrent events in patients with diabetes or after myocardial infarction remain common. This study aimed to assess the association between FFR-negative but high-risk nonculprit lesions and clinical outcomes.

Methods: This is a patient-level pooled analysis of the prospective natural-history COMBINE (OCT-FFR) study (Optical Coherence Tomography Morphologic and Fractional Flow Reserve Assessment in Diabetes Mellitus Patients) and PECTUS-obs study (Identification of Risk Factors for Acute Coronary Events by OCT After STEMI and NSTEMI Patients With Residual Non- Flow Limiting Lesions).

Detection of clinically relevant variants in the gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL.

In chronic lymphocytic leukemia, the reliability of next-generation sequencing (NGS) to detect variants ≤10% allelic frequency (low-VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.

Recommendations for reporting and evaluating proton therapy beyond dose and constant relative biological effectiveness.

Background And Purpose: In proton therapy, a relative biological effectiveness (RBE) of 1.1 is used to convert proton dose into an equivalent photon dose. However, RBE varies with tissue type, fraction dose, and beam quality parameters beyond dose such as linear energy transfer (LET) raising concerns about increased local effectiveness and potential toxicity.

Current practices in prevention, screening, and treatment of diabetes in kidney transplant recipients: European survey highlights from the ERA DESCARTES Working Group.

Background: Although post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplantation, there are few data on prevention, optimal screening, and treatment strategies.

Methods: The European Renal Association's DESCARTES working group distributed a web-based survey to European transplant centres to gather information on risk assessment, screening procedures, and management practices for preventing and treating PTDM in kidney transplant recipients.

Results: Answers were obtained from 121/241 transplant centres (50%) across 15 European countries.

Unmet medical needs definition and incentives: stakeholders perspectives on the reform of the EU pharmaceutical legislation.

Introduction: The 2020 pharmaceutical strategy for Europe stressed that rethinking regulatory policies to foster innovation in disease areas with unmet medical needs (UMN) is one of the European Commission's (EC) priority areas. To understand stakeholders' views regarding appropriate UMN criteria and incentives, the EC developed a survey and launched it for public consultation between September and December 2021. This study aims to assess stakeholders' views on the policy revisions proposed by the EC, particularly those regarding the definition of UMN, its criteria and incentives and evaluate how stakeholders' views are reflected in the proposed reform of the EU pharmaceutical legislation of 2023.

Understanding recurrent groin pain following periacetabular osteotomy: assessment of psoas tendon mechanics using discrete element analysis.

Recurrent groin pain following periacetabular osteotomy (PAO) is a challenging problem. The purpose of our study was to evaluate the position and dynamics of the psoas tendon as a potential cause for recurrent groin pain following PAO. A total of 386 PAO procedures, performed between January 2013 and January 2020, were identified from a single surgeon series.

Victorian Institute of Sport Assessment questionnaire specifically tailored for greater trochanteric pain syndrome for the Dutch population.

Greater trochanteric pain syndrome (GTPS) is a highly prevalent condition characterized by lateral hip and thigh pain. The Victorian Institute of Sport Assessment (VISA) questionnaire specifically tailored for GTPS (VISA-G) questionnaire was developed for the purpose of assessing and quantifying the severity of symptoms related to gluteal tendinopathy or GTPS. It is commonly used in research and clinical settings to evaluate the impact of GTPS on patient function and quality of life.

Historically Polluted Area Increases Human Exposure Risks to Polychlorinated Naphthalenes through Waterfowl Egg Consumption.

Polychlorinated naphthalenes (PCNs), which are ubiquitous in the environment, are listed as persistent organic pollutants under the Stockholm Convention. Poultry can be exposed to PCNs via feed and breeding environments, leading to PCNs accumulation in eggs. However, information on PCNs in eggs from waterfowl raised in contaminated regions is scarce.

From speech acts to communicative acts: social network debates about sexual consent.

Introduction: Understanding consent is essential to combat sexual violence, a deeply rooted social problem. Amidst its complexities, the scientific literature has emphasized the shortcomings of only considering the speech act-whether the victim-survivor said "yes" or not. Instead, sociological research underscores the need to analyze the whole communicative act where different elements lead to either a power relationship where there is no consent or a dialogic relationship where freedom is granted.

Investigating the impact of acceptance and commitment therapy for mental healthcare professionals: the effect on patients´ self-stigmatization, a pilot study.

Background: A significant proportion of mental health care professionals (MHCPs) hold stigmatizing attitudes about their patients. When patients perceive and internalize these beliefs, self-stigmatization can increase. Acceptance and Commitment Therapy (ACT) may decrease stigmatizing attitudes by changing the 'us' versus 'them' thinking into continuum beliefs.

Quantitative ultrasonography of the foot muscles: a comprehensive perspective on reliability.

Background: Quantitative ultrasound imaging is a popular technique to assess the structural properties of the intrinsic and extrinsic foot muscles. Although several studies examined test-retest reliability, specific gaps remain in assessing inter-rater reliability, particularly distinguishing between image acquisition and muscle measurement. Additionally, these studies utilized equipment that may not be generalizable across both clinical and research settings and often involved small sample sizes without prior sample size calculations.

Oncogenic mutant KRAS inhibition through oxidation at cysteine 118.

Specific reactive oxygen species activate the GTPase Kirsten rat sarcoma virus (KRAS) by reacting with cysteine 118 (C118), leading to an electron transfer between C118 and nucleoside guanosine diphosphate (GDP), which causes the release of GDP. Here, we have mimicked permanent oxidation of human KRAS at C118 by replacing C118 with aspartic acid (C118D) in KRAS to show that oncogenic mutant KRAS is selectively inhibited via oxidation at C118, both in vitro and in vivo. Moreover, the combined treatment of hydrogen-peroxide-producing pro-oxidant paraquat and nitric-oxide-producing inhibitor N(ω)-nitro-l-arginine methyl ester selectively inhibits human mutant KRAS activity by inducing oxidization at C118.

Vitronectin regulates lung tissue remodeling and emphysema in chronic obstructive pulmonary disease.

Vitronectin (VTN) is an important extracellular matrix protein in tissue remodeling, but its role in COPD is unknown. We show that VTN regulates tissue remodeling through urokinase plasminogen activator (uPA) signaling pathway in COPD. In human COPD airways and bronchoepithelial cells and the airways of mice with cigarette smoke (CS)-induced experimental COPD, VTN protein was not changed, but downstream uPA signaling was altered (increased plasminogen activator inhibitor-1, uPAR) that induced collagen and airway remodeling.

Sex dimorphic associations of Prader-Willi imprinted gene expressions in umbilical cord with prenatal and postnatal growth in healthy infants.

Background: The impact of Prader-Willi syndrome (PWS) domain gene expression on the growth of healthy children is not well understood. This study investigated associations between PWS domain gene expression in umbilical cord tissue and prenatal and postnatal growth, considering potential sex differences.

Methods: Relative gene expression of paternally expressed MAGEL2, NDN, and SNURF-SNRPN, and the small nucleolar RNAs SNORD116 and SNORD115 were determined by real-time quantitative polymerase chain reaction in umbilical cord tissue from 122 healthy newborns (59 girls and 63 boys).

Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial.

Patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer (BC) have low pathological complete response (pCR) rates with neoadjuvant chemotherapy. A subset of ER+/HER2- BC contains dense lymphocytic infiltration. We hypothesized that addition of an anti-programmed death 1 agent may increase pCR rates in this BC subtype.

TLE4 is a repressor of the oncogenic activity of TLX3 in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological disease originating from the malignant transformation of T-cell progenitors, caused by the accumulation of genetic aberrations. One-fifth of T-ALL patients are characterized by ectopic expression of the homeobox transcription factor TLX3. However, the role of TLX3 in T-ALL remains elusive, partly due to the lack of suitable study models.

Insights from a century of data reveal global trends in ex situ living plant collections.

Ex situ living plant collections play a crucial role in providing nature-based solutions to twenty-first century global challenges. However, the complex dynamics of these artificial ecosystems are poorly quantified and understood, affecting biodiversity storage, conservation and utilization. To evaluate the management of ex situ plant diversity, we analysed a century of data comprising 2.

Time to HIV viral rebound and frequency of post-treatment control after analytical interruption of antiretroviral therapy: an individual data-based meta-analysis of 24 prospective studies.

The only current strategy to test efficacy of novel interventions for sustained HIV control without antiretroviral therapy (ART) among people with HIV (PWH) is through an analytical treatment interruption (ATI). Inclusion of 'placebo' controls in ATIs poses ethical, logistical, and economic challenges. To understand viral dynamics and rates of post-treatment control (PTC) after ATI among PWH receiving either placebo or no intervention, we undertook an individual-participant data meta-analysis.

A novel, dominant disease mechanism of distal renal tubular acidosis with specific variants in ATP6V1B1.

Background And Hypothesis: ATP6V1B1 encodes a subunit of the vacuolar H+-ATPase and pathogenic variants are associated with autosomal recessive distal renal tubular acidosis (dRTA) with deafness. Heterozygous variants predicted to affect a specific amino acid, Arg394, have been recurrently reported in dRTA but their significance has been unclear. We hypothesised that these variants are associated with a dominant disease mechanism.

ASRA Pain Medicine consensus practice infection control guidelines for regional anesthesia and pain medicine.

Background: To provide recommendations on risk mitigation, diagnosis and treatment of infectious complications associated with the practice of regional anesthesia, acute and chronic pain management.

Methods: Following board approval, in 2020 the American Society of Regional Anesthesia and Pain Medicine (ASRA Pain Medicine) commissioned evidence-based guidelines for best practices for infection control. More than 80 research questions were developed and literature searches undertaken by assigned working groups comprising four to five members.