Discordance, accuracy and reproducibility study of pathologists' diagnosis of melanoma and melanocytic tumors.

Accurate melanoma diagnosis is crucial for patient outcomes and reliability of AI diagnostic tools. We assess interrater variability among eight expert pathologists reviewing histopathological images and clinical metadata of 792 melanoma-suspicious lesions prospectively collected at eight German hospitals. Moreover, we provide access to the largest panel-validated dataset featuring dermoscopic and histopathological images with metadata.

Association between serum 25-hydroxyvitamin D concentrations and urinary vitamin D metabolite concentrations measured by the NLucVDR assay.

It is well known that vitamin D is essential for human health; however, many people suffer from vitamin D deficiency or insufficiency worldwide, including in Japan. Serum 25-hydroxyvitamin D (25(OH)D) concentrations are typically measured to evaluate vitamin D status. In a previous study, we demonstrated that the concentrations of vitamin D metabolites in urine, measured using the NLucVDR assay system composed of a split-type nanoluciferase and the ligand-binding domain (LBD) of the human vitamin D receptor, correlated with serum 25(OH)D concentrations measured using liquid chromatography-mass spectrometry (LC-MS) or electrochemiluminescence immunoassays (ECLIAs).

Consensus and guidelines on diagnosis and management of polypoidal choroidal vasculopathy (PCV) from the Asia-Pacific Vitreo-retina Society (APVRS).

A panel of 21 international experts are formed by the Asia-Pacific Vitreo-retina Society to work out the consensus and guidelines on polypoidal choroidal vasculopathy (PCV). PCV is a common subtype of neovascular age-related macular degeneration and is more prevalent in Asian populations. Recent advancement in imaging technology allows greater understanding of the disease process of PCV.

Leucine-rich alpha-2 glycoprotein in combination with C-reactive protein for predicting endoscopic activity in Crohn's disease: a single-centre, cross-sectional study.

Background And Objective: Leucine-rich alpha-2 glycoprotein (LRG) is a novel biomarker for Crohn's disease (CD). The utility of combination use of LRG and C-reactive protein (CRP) has not been reported. This study aimed to investigate the diagnostic performance of LRG in combination with CRP to predict endoscopic activity.

A persistent bacterial Regiella transinfection in the bird cherry-oat aphid Rhopalosiphum padi increasing host fitness and decreasing plant virus transmission.

Background: The bird cherry-oat aphid, Rhopalosiphum padi, is a major pest of agriculture due to its ability to directly damage crops and transmit plant viruses. As industries move away from chemical pest control, there is interest in exploring new options to suppress the impact of this pest.

Results: We describe the production of a transinfected line of R.

The risks of pityriasis rosea in pregnancy: a review.

Objective: This review aims to consolidate available evidence, identify research gaps, and advocate for a more informed approach to the management of pityriasis rosea in pregnant individuals.

Data Sources: PubMed, Web of Science, and Directory of Open Access Journals were systematically searched based on the keywords "pityriasis rosea," "pityriasis circinate," "roseola annulate," "herpes tonsurans maculosus," "herald patch," and "pregnancy" on January 25, 2024 for publications between 1950 to 2024.

Study Selection: Studies containing outcomes data for pregnant patients with established PR were included.

Exploring the relationship between melanopsin gene variants, sleep, and markers of brain health.

Introduction: Melanopsin is a photopigment with roles in mediating sleep and circadian-related processes, which are often disrupted in Alzheimer's disease (AD). Melanopsin also impacts cognition and synaptogenesis. This study investigated the associations between melanopsin genetic variants, sleep, and markers of brain health.

Tofersen for SOD1 amyotrophic lateral sclerosis: a systematic review and meta-analysis.

Objective: Tofersen, an antisense oligonucleotide, has recently received FDA and EMA approval for treating amyotrophic lateral sclerosis (ALS) in adults with SOD1 gene mutations. This systematic review and meta-analysis synthesized evidence on tofersen's safety and efficacy in patients with SOD1-related ALS.

Methods: A comprehensive search of three databases was conducted from inception through October 2024.

[The 6th Year of the Study of Human Medicine is Mainly Orientated to Practice: a Pilot Study with a Digital Logbook].

Digital learning resources are in increasing demand, especially in the light of the planned reform of the medical licensing regulations for 2028. In a pilot project, we digitised and evaluated a logbook for students in their practical year (PJ).The aim of this study is to evaluate the digital and non-digital PJ logbooks.

[Cutaneous ulceration in dermatomyositis : Case reports with positive anti-NXP-2/anti-TIF1-gamma antibody status].

Painful ulcerations developed in a 33-year-old woman with anti-NXP-2-positive dermatomyositis in the facial and trunk areas and a 67-year-old woman with TIF1-gamma-positive dermatomyositis on the hands, while undergoing systemic therapy with azathioprine or low-dose methylprednisolone and cyclic administration of intravenous immunoglobulins (IVIG), respectively. In the laboratory workup, the anti-MDA‑5 antibody status remained negative and the creatine kinase (CK) normal in both patients, while histopathological examinations were nonspecific. Intensive topical class 4 corticosteroid therapy and continuation of the immunosuppressive or immunomodulating therapy led to healing of the ulcerative skin lesions.

Biomechanics of flail chest injuries: tidal volume and respiratory work changes in multiple segmental rib fractures.

Background: Flail chest (FC) injuries are segmental osseous injuries of the thorax that typically result from high-energy blunt trauma and regularly occur in multiple trauma (MT) patients. FC injuries are associated with paradoxical chest wall movements and, thus, have a high risk of respiratory insufficiency or even death. An increasing number of studies recommend an early surgical stabilization of FC injuries, but a definite trigger that would indicate surgery has, thus far, not been identified.

Olutasidenib in combination with azacitidine induces durable complete remissions in patients with relapsed or refractory mIDH1 acute myeloid leukemia: a multicohort open-label phase 1/2 trial.

Background: Olutasidenib is a potent, selective, oral, small molecule inhibitor of mutant IDH1 (mIDH1) which induced durable remissions in high-risk, relapsed/refractory (R/R) mIDH1 AML patients in a phase 1/2 trial. We present a pooled analysis from multiple cohorts of the phase 1/2 trial of patients with R/R AML who received combination olutasidenib and azacitidine therapy.

Methods: Adult patients with mIDH1 AML received 150 mg olutasidenib twice daily plus standard-of-care azacitidine (OLU + AZA) and were evaluated for response and safety.

Why and how should we simulate platform trials? Learnings from EU-PEARL.

Background: Platform trials are innovative clinical trials governed by a master protocol that allows for the evaluation of multiple investigational treatments that enter and leave the trial over time. Interest in platform trials has been steadily increasing over the last decade. Due to their highly adaptive nature, platform trials provide sufficient flexibility to customize important trial design aspects to the requirements of both the specific disease under investigation and the different stakeholders.

Design and development of pyrazol-5-ylbenzamide derivatives containing chiral oxazoline moiety as fungicides based on molecular docking.

Background: Development of novel chiral antifungal agents for effective control of plant pathogens is urgently needed. In this study, a series of pyrazol-5-yl-benzamide derivatives containing chiral oxazoline moiety were rationally designed and developed based on molecular docking.

Results: The in vitro antifungal assay results indicated that compounds (rac)-4h (R = Et), (S)-4 h (R = S-Et) and (R)-4 h (R = R-Et) exhibited remarkable antifungal activities against Valsa mali with median effective concentration (EC) values of 0.

Simulation of clinical trials of oral treprostinil in pulmonary arterial hypertension using a virtual population.

Challenges in drug development for rare diseases such as pulmonary arterial hypertension can be addressed through the use of mathematical modeling. In this study, a quantitative systems pharmacology model of pulmonary arterial hypertension pathophysiology and pharmacology was used to predict changes in pulmonary vascular resistance and six-minute walk distance in the context of oral treprostinil clinical studies. We generated a virtual population that spanned the range of clinical observations and then calibrated virtual patient-specific weights to match clinical trials.

Effect of Characteristic Inflammatory and Structural Pelvic Magnetic Resonance Imaging Lesions on Expert Assessment of Axial Juvenile Spondyloarthritis.

Objective: To evaluate the influence of pelvic magnetic resonance imaging (MRI) findings on axial disease assessment in juvenile spondyloarthritis (JSpA).

Methods: This was a cross-sectional study of patients with JSpA with suspected axial disease. Three experts reviewed each case and rated their confidence (-3 to +3) in the presence of axial disease, first with clinical data and second with clinical and MRI data.

Dynamic Covalent Sulfur-Selenium Rich Polymers via Inverse Vulcanization for High Refractive Index, High Transmittance, and UV Shielding Materials.

Recent advancements in inverse vulcanization have led to the development of sulfur-rich polymers with diverse applications. However, progress is constrained by the harsh high-temperature reaction conditions, limited applicability, and the generation of hazardous HS gas. This study presents an induced IV method utilizing selenium octanoic acid, yielding sulfur-selenium rich polymers with full atom economy, even at a low-temperatures of 100-120 °C.

Enabling next-generation engineered TCR-T therapies based on high-throughput TCR discovery from diagnostic tumor biopsies.

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) can mediate tumor regression, including complete and durable responses, in a range of solid cancers, most notably in melanoma. However, its wider application and efficacy has been restricted by the limited accessibility, proliferative capacity and effector function of tumor-specific TIL. Here, we develop a platform for the efficient identification of tumor-specific TCR genes from diagnostic tumor biopsies, including core-needle biopsies frozen in a non-viable format, to enable engineered T cell therapy.

Quantitative prediction of toxicological points of departure using two-stage machine learning models: A new approach methodology (NAM) for chemical risk assessment.

Point of departure (POD) is a concept used in risk assessment to calculate the reference dose of exposure that is likely to have no appreciable risk on health. POD can be directly utilized from no observed adverse effect levels (NOAEL) which is the dose or exposure level at which there is little or no risk of adverse effects. However, NOAEL values are unavailable for most of the chemicals due to inconsistent animal toxicity data.

Measurement Properties of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia.

Introduction: The Friedreich Ataxia Rating Scale-Activities of Daily Living (FARS-ADL) is a valid, highly utilized measure for assessing ADL impacts in patients with Friedreich ataxia. We provide evidence of the psychometric validity of the FARS-ADL in two cohorts of patients with spinocerebellar ataxia (SCA).

Methods: Using data from a cohort of real-world subjects with SCA (recruited at Massachusetts General Hospital [MGH]; n = 33) and a phase 3 trial of troriluzole in adults with SCA (NCT03701399 [Study 206]; n = 217), comprising a subset of patients with the SCA3 genotype (n = 89), the psychometric measurement properties and minimal change thresholds of the FARS-ADL were examined.

Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms.

Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms.

Arrhythmogenic Right Ventricular Cardiomyopathy: The Importance of Biventricular Strain in Risk-Stratification.

Despite arrhythmogenic right ventricular cardiomyopathy (ARVC) being predominantly a right ventricular (RV) disease, concomitant left ventricular (LV) involvement has been recognized. ARVC is diagnosed by the RV-centric 2010 Task Force Criteria(TFC) using routine echocardiography, but previous studies have suggested that strain imaging may be more sensitive to detect RV and LV dysfunction. No data however are available regarding the additional value of combining biventricular strain for risk stratification.

Convertible metal-backed glenoid in total shoulder arthroplasty.

Aims: The aim of this study was to report long-term clinical outcomes of a modern convertible metal-backed glenoid (MBG) in total shoulder arthroplasty (TSA).

Methods: After a minimum of 15 years, a previously studied cohort of 35 patients who received a modern convertible MBG during the period 1996 to 2005 was contacted for clinical and radiological follow-up. At last follow-up, patients were evaluated radiologically and clinically according to the Constant Score, Simple Shoulder Test, and visual analogue scale for pain.