First-Line Chemo-Immunotherapy in SCLC: Outcomes of a Binational Real-World Study.

Introduction: SCLC is characterized by aggressiveness and limited treatment options, especially in extensive-stage SCLC (ES-SCLC). Immunotherapy added to the platinum-etoposide combination has recently become standard in this setting. This retrospective study aims to evaluate the real-world effectiveness of chemo-immunotherapy in patients with ES-SCLC, focusing on subpopulations excluded from clinical trials.

Multi-dimensional analyses identify genes of high priority for pancreatic cancer research.

Pancreatic ductal adenocarcinoma (PDAC) is a drug resistant and lethal cancer. Identification of the genes that consistently show altered expression across patients' cohorts can expose effective therapeutic targets and strategies. To identify such genes, we separately analyzed five human PDAC microarray datasets.

Tuft cells transdifferentiate to neural-like progenitor cells in the progression of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is partly initiated through the transdifferentiation of acinar cells to metaplasia, which progresses to neoplasia and cancer. Tuft cells (TCs) are chemosensory cells not found in the normal pancreas but arise in cancer precursor lesions and diminish during progression to carcinoma. These metaplastic TCs (mTCs) suppress tumor progression through communication with the tumor microenvironment, but their fate during progression is unknown.

HMGA2 Expression Predicts Subtype, Survival, and Treatment Outcome in Pancreatic Ductal Adenocarcinoma.

Purpose: To establish HMGA2 as a marker of basal-like disease in pancreatic ductal adenocarcinoma (PDAC) and explore its use as a biomarker for prognosis and treatment resistance.

Experimental Design: We identified high expression of HMGA2 in basal PDAC cells in a scRNAseq Atlas of 172 patient samples. We then analyzed HMGA2 expression, along with expression of the classical marker GATA6, in a cohort of 580 PDAC samples with multiplex immunohistochemistry.

Higher expression of mir-31-5p is associated with reduced risk of head and neck keloid recurrence following surgical resection.

Objective: In this study, we aimed to evaluate mir-31-5p as a prognostic biomarker of keloid disease (KD) recurrence using a retrospective, treatment naïve, surgical cohort of head and neck KD cases from Henry Ford Health.

Methods: Using a tissue microarray, mir-31-5p expression was measured with miRNAscope, and mir-31-5p cell positivity was determined with QuPath. Logistic regression was used to test the association between mir-31-5p positive cells and KD recurrence at 1 year.

Human pancreatic cancer single cell atlas reveals association of CXCL10+ fibroblasts and basal subtype tumor cells.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) patients with tumors enriched for the basal-like molecular subtype exhibit enhanced resistance to standard of care treatments and have significantly worse overall survival (OS) compared to patients with classical subtype enriched tumors. It is important to develop genomic resources, enabling identification of novel putative targets in a statistically rigorous manner.

Experimental Design: We compiled a single cell RNA sequencing (scRNAseq) atlas of the human pancreas with 229 patient samples, aggregated from publicly available raw data.

Outcomes of primary total hip arthroplasty in patients with Ehlers Danlos Syndromes.

Background: The Ehlers Danlos Syndromes (EDS) are inherited in an autosomal dominant pattern and patients classically present with hypermobility, skin hyper-elasticity, blood vessel fragility and atrophic scarring. Due to hypermobility, disorders such as joint pain and early arthritis are common. The aim of this study was to assess clinical and radiological outcomes of total hip arthroplasty (THA) in patients with EDS treated in a high volume orthopaedic centre.

Increasing Importance and Costs Associated With Publishing for Dermatology Residency Applicants.

The financial costs associated with publishing in academic journals have steadily risen in recent years, reflected by higher publishing fees and the emergence of open access (OA) publishing models. Research remains an essential part of academia and has special significance for residency applicants. Due to recent changes in some objective measures used to rank residency applicants, such as abandoning numerical United States Medical Licensing Examination (USMLE) Step 1 scores and transitioning pre-clinical grades to Pass/Fail, other objective measures have gained significance: in particular, the quality and quantity of research activities including manuscripts, abstracts, and presentations have become more important in residency applications.

SPACE: Spatially variable gene clustering adjusting for cell type effect for improved spatial domain detection.

Recent advances in spatial transcriptomics have significantly deepened our understanding of biology. A primary focus has been identifying spatially variable genes (SVGs) which are crucial for downstream tasks like spatial domain detection. Traditional methods often use all or a set number of top SVGs for this purpose.

Socioeconomic factors, sleep timing and duration, and amygdala resting-state functional connectivity in children.

Introduction: Reduced sleep health has been consistently linked with increased negative emotion in children. While sleep characteristics have been associated with neural function in adults and adolescents, much less is known about these associations in children while considering socioeconomic context. In this study, we examined the associations among socioeconomic factors, sleep duration and timing, and resting-state functional connectivity (rsFC) of the amygdala in children.

Interpretation and reporting considerations of low-level DNA profiles following MinElute® purification of PowerPlex® 21 amplified products.

The generation of high-quality DNA profiles from trace amounts of DNA continues to be an issue in forensic casework. Several methods have been proposed over the years to increase recovery rates for low input DNA, including purification of PCR products, an increase in PCR cycle numbers and increasing injection time or voltage during electrophoresis. In this study, the characteristics of DNA profiles generated using QIAGEN MinElute® purification of Promega PowerPlex® 21 amplified products for low DNA input samples, ranging from 80 pg down to 4 pg, were evaluated.

Netrin G1 Ligand is a new stromal immunomodulator that promotes pancreatic cancer.

Unlabelled: Understanding pancreatic cancer biology is fundamental for identifying new targets and for developing more effective therapies. In particular, the contribution of the stromal microenvironment to pancreatic cancer tumorigenesis requires further exploration. Here, we report the stromal roles of the synaptic protein Netrin G1 Ligand (NGL-1) in pancreatic cancer, uncovering its pro-tumor functions in cancer-associated fibroblasts and in immune cells.

Evaluation of post-PCR purification methods and subsequent optimisation of the MinElute® PCR Purification Kit for low input DNA samples amplified with PowerPlex® 21.

Weak and partial DNA profiles are commonly encountered within forensic casework due to amplification of low DNA input samples. One option for increasing allelic detection in such samples is the purification of amplified PCR product using commercially available column-based methods. In this study, four commercially available post-PCR purification methods, QIAGEN MinElute®, Independent Forensics Amplicon™ Rx, Millipore Microcon® and Thermo Fisher Scientific ExoSAP-IT™ were evaluated, comparing the quality of PowerPlex® 21 DNA profiles produced to the standard DNA profile generated prior to purification.

Developing "The Health After Cancer Podcast" to amplify cancer survivors' voices through digital storytelling.

Background: Cancer survivors experience complex medical and psychosocial challenges after a cancer diagnosis, leading to unmet informational and emotional needs. There is a paucity of cancer survivorship educational resources co-created by survivors and medical professionals.

Objective: Our aim was to create an educational resource for cancer survivors, caregivers, and medical professionals that would leverage digital storytelling to address survivorship topics.

Cancer Survivorship at Stanford Cancer Institute.

The Stanford Cancer Survivorship Program is a key initiative of Stanford Cancer Institute. The program's mission is to improve the experience and outcomes of patients and family caregivers throughout all phases of the cancer trajectory by advancing survivorship research, clinical care, and education. The four pillars of the program include clinical care delivery with a focus on primary care-survivorship collaboration and expanding specialty services, education and training of healthcare professionals, transdisciplinary patient-oriented research, and community engagement.

Lp(a) and risk of cardiovascular disease - A review of existing evidence and emerging concepts.

Cardiovascular disease (CVD) remains the leading cause of death among adults in the United States. There has been significant advancement in the diagnosis and treatment of atherosclerotic cardiovascular disease (ASCVD) and its underlying risk factors. In certain populations, there remains a significant residual risk despite adequate lowering of low-density lipoprotein cholesterol (LDL-C) and control of traditional risk factors.

Genome-wide association study of age at puberty and its (co)variances with fertility and stature in growing and lactating Holstein-Friesian dairy cattle.

Reproductive performance is a key determinant of cow longevity in a pasture-based, seasonal dairy system. Unfortunately, direct fertility phenotypes such as intercalving interval or pregnancy rate tend to have low heritabilities and occur relatively late in an animal's life. In contrast, age at puberty (AGEP) is a moderately heritable, early-in-life trait that may be estimated using an animal's age at first measured elevation in blood plasma progesterone (AGEP4) concentrations.

Modeling Molecular Pathogenesis of Idiopathic Pulmonary Fibrosis-Associated Lung Cancer in Mice.

Unlabelled: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive, often fatal loss of lung function due to overactive collagen production and tissue scarring. Patients with IPF have a sevenfold-increased risk of developing lung cancer. The COVID-19 pandemic has increased the number of patients with lung diseases, and infection can worsen prognoses for those with chronic lung diseases and disease-associated cancer.

Notch Signaling Regulates Immunosuppressive Tumor-Associated Macrophage Function in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. The poor survival of patients with PDA has been attributed to a high rate of early metastasis and low efficacy of current therapies, which partly result from its complex immunosuppressive tumor microenvironment. Previous studies from our group and others have shown that tumor-associated macrophages (TAM) are instrumental in maintaining immunosuppression in PDA.

KRT17high/CXCL8+ Tumor Cells Display Both Classical and Basal Features and Regulate Myeloid Infiltration in the Pancreatic Cancer Microenvironment.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is generally divided in two subtypes, classical and basal. Recently, single-cell RNA sequencing has uncovered the coexistence of basal and classical cancer cells, as well as intermediary cancer cells, in individual tumors. The latter remains poorly understood; here, we sought to characterize them using a multimodal approach.

Multi-omics analysis of metastatic pancreatic cancer reveals an immunosuppressive landscape.

Immune cell populations play key functional roles in tumor growth and metastasis, and multi-omic approaches can map cellular interactions to identify targets for highly immunosuppressive and treatment resistant cancers. In this issue of Med, Zhang et al. investigate the immune cell landscape of advanced pancreatic cancer to understand the mechanisms underlying liver metastasis.