Pathologists Providing Direct Patient Care in Thoracic Transplant: Same Objective, Different Scope.

Context.—: Cardiac and pulmonary allograft recipients represent a unique population, frequently interacting with support groups and exhibiting intense curiosity about their pathology. Like other solid organ transplant patients, they have enduring and frequent interaction with the laboratory for routine allograft surveillance.

Implementing palliative care in the intensive care unit: a systematic review and mapping of knowledge to the implementation research logic model.

Purpose: The importance and effectiveness of palliative care (PC) in intensive care units (ICU) are known. Less is known about the implementation and integration of ICU-based PC interventions. This systematic review aims to use a modified implementation research logic model (IRLM) to identify, map, and synthesise evidence on implementation of ICU-PC (primary and/or specialist) interventions.

Somatic mutations in 3929 HPV positive cervical cells associated with infection outcome and HPV type.

Invasive cervical cancers (ICC), caused by HPV infections, have a heterogeneous molecular landscape. We investigate the detection, timing, and HPV type specificity of somatic mutations in 3929 HPV-positive exfoliated cervical cell samples from individuals undergoing cervical screening in the U.S.

A 62-Year-Old Woman With Cough, Dyspnea, and Diffuse Lung Nodules.

A 62-year-old woman came to our hospital with worsening cough and dyspnea over the preceding week, during which time she had been treated with azithromycin and prednisone for suspected pneumonia. She had no fever, chills, or sweats, but her cough had become productive of clear to blood-tinged phlegm during the interval. Medical history was significant for insulin-dependent diabetes mellitus and OSA.

A Fragment-Based Competitive F LB-NMR Platform For Hotspot-Directed Ligand Profiling.

Ligand binding hotspots are regions of protein surfaces that form particularly favourable interactions with small molecule pharmacophores. Targeting interactions with these hotspots maximises the efficiency of ligand binding. Existing methods are capable of identifying hotspots but often lack assays to quantify ligand binding and direct elaboration at these sites.

Central Posterior Envelopes for Bayesian Functional Principal Component Analysis.

Bayesian methods provide direct inference in functional data analysis applications without reliance on bootstrap techniques. A major tool in functional data applications is the functional principal component analysis which decomposes the data around a common mean function and identifies leading directions of variation. Bayesian functional principal components analysis (BFPCA) provides uncertainty quantification on the estimated functional model components via the posterior samples obtained.

A Semi-Mechanistic Population Pharmacokinetic Model of Noscapine in Healthy Subjects Considering Hepatic First-Pass Extraction and CYP2C9 Genotypes.

Introduction: Noscapine is a commonly used cough suppressant, with ongoing research on its anti-inflammatory and anti-tumor properties. The drug has a pronounced pharmacokinetic variability.

Objective: This evaluation aims to describe the pharmacokinetics of noscapine using a semi-mechanistic population pharmacokinetic model and to identify covariates that could explain inter-individual pharmacokinetic variability.

Granulomatous Lung Diseases: A Practical Approach and Review of Common Entities.

Granulomas are frequently encountered by pathologists in all types of lung specimens and arise from diverse etiologies. They should always be reported as necrotizing or non-necrotizing, with microorganism stains performed to evaluate for infection. With attention to distribution, quality (poorly vs well-formed), associated features, and correlation with clinical, radiologic, and laboratory data, the differential diagnosis for granulomatous lung disease can usually be narrowed to a clinically helpful "short list.

Improving the etection, ssessment, anagement and revention of elirium in Hospices (the DAMPen-D study): Feasibility study of a flexible and scalable implementation strategy to deliver guideline-adherent delirium care.

Background: Delirium is a complex condition, stressful for all involved. Although highly prevalent in palliative care settings, it remains underdiagnosed and associated with poor outcomes. Guideline-adherent delirium care may improve its detection, assessment and management.

Prognostic Immunohistochemistry for Ki-67 and OTP on Small Biopsies of Pulmonary Carcinoid Tumors: Ki-67 Index Predicts Progression-free Survival and Atypical Histology.

Prognostic stratification of pulmonary carcinoids into "typical" and "atypical" categories requires examination of large tissue volume. However, there is a need for tools that provide similar prognostic information on small biopsy samples. Ki-67 and OTP immunohistochemistry have shown promising prognostic value in studies of resected pulmonary carcinoids, but prognostic value when using biopsy/cytology specimens is unclear.

Chemical Validation of Phosphopantetheine Adenylyltransferase Using Fragment Linking and CRISPR Interference.

The coenzyme A (CoA) biosynthesis pathway has attracted attention as a potential target for much-needed novel antimicrobial drugs, including for the treatment of tuberculosis (TB), the lethal disease caused by (). Seeking to identify inhibitors of phosphopantetheine adenylyltransferase (PPAT), the enzyme that catalyses the penultimate step in CoA biosynthesis, we performed a fragment screen. In doing so, we discovered three series of fragments that occupy distinct regions of the PPAT active site, presenting a unique opportunity for fragment linking.

Pulmonary gangliocytic paraganglioma: An under-recognized mimic of carcinoid tumor.

Gangliocytic paragangliomas are rare neoplasms occurring almost exclusively in the ampullary region of the gastrointestinal tract. Although these tumors are not typically considered in the differential diagnosis of primary pulmonary neoplasia, 5 cases of primary pulmonary gangliocytic paragangliomas have been previously reported. Herein we report our experience with 3 additional examples, all referred to our Anatomic Pathology Consultation service.

Primary Pulmonary Myxoid Sarcoma and Thoracic Angiomatoid Fibrous Histiocytoma: Two Sides of the Same Coin?

Primary pulmonary myxoid sarcoma (PPMS) and thoracic angiomatoid fibrous histiocytoma (AFH) are rare neoplasms with EWSR1 fusions and overlapping morphology. Both tumor types often show epithelial membrane antigen expression, but AFH characteristically co-expresses desmin. We encountered a case of PPMS with the unexpected finding of patchy, strong anaplastic lymphoma kinase (ALK) (previously reported in AFH) and synaptophysin expression.

The ATR inhibitor ceralasertib potentiates cancer checkpoint immunotherapy by regulating the tumor microenvironment.

The Ataxia telangiectasia and Rad3-related (ATR) inhibitor ceralasertib in combination with the PD-L1 antibody durvalumab demonstrated encouraging clinical benefit in melanoma and lung cancer patients who progressed on immunotherapy. Here we show that modelling of intermittent ceralasertib treatment in mouse tumor models reveals CD8 T-cell dependent antitumor activity, which is separate from the effects on tumor cells. Ceralasertib suppresses proliferating CD8 T-cells on treatment which is rapidly reversed off-treatment.

Channel morphological change monitoring using high-resolution LiDAR-derived DEM and multi-temporal imageries.

Natural processes and human activities both cause morphological changes in channels. Remote sensing products are often used to assess planform changes, but they tend to overlook vertical changes. However, considering both planform and vertical changes is crucial for a comprehensive evaluation of morphological changes.

New UK palliative medicine consultants: clinical and non-clinical preparedness after higher specialty training.

Objectives: Higher specialty trainees are expected to achieve clinical and non-clinical skills during training in preparation for a consultant role. However, evidence from many specialties from different countries suggests that new consultants are less prepared in non-clinical skills. The transition from trainee to a consultant phase can be challenging.

Clinicopathologic and Molecular Characteristics of Resected Thoracic Mass Lesions in the Pediatric Population: A 25-Year Institutional Experience From a Tertiary Care Center.

Context.—: Primary thoracic neoplasms are rare in children, whereas nonneoplastic mass lesions or cysts and metastases are more common, and there is a relative paucity of comprehensive histopathologic and molecular data.

Objective.

Insights into the mechanisms and structure of breakage-fusion-bridge cycles in cervical cancer using long-read sequencing.

Cervical cancer is caused by human papillomavirus (HPV) infection, has few approved targeted therapeutics, and is the most common cause of cancer death in low-resource countries. We characterized 19 cervical and four head and neck cancer cell lines using long-read DNA and RNA sequencing and identified the HPV types, HPV integration sites, chromosomal alterations, and cancer driver mutations. Structural variation analysis revealed telomeric deletions associated with DNA inversions resulting from breakage-fusion-bridge (BFB) cycles.

Micro and nano plastics release from a single absorbable suture into simulated body fluid.

Synthetic polymers are widely used in medical devices and implants where biocompatibility and mechanical strength are key enablers of emerging technologies. One concern that has not been widely studied is the potential of their microplastics (MPs) release. Here we studied the levels of MP debris released following 8-week in vitro tests on three typical polyglycolic acid (PGA) based absorbable sutures (PGA 100, PGA 90 and PGA 75) and two nonabsorbable sutures (polypropylene-PP and polyamide-PA) in simulated body fluid.