Data-driven synapse classification reveals a logic of glutamate receptor composition.

The rich diversity of synapses facilitates the capacity of neural circuits to transmit, process and store information. Here, we used multiplex super-resolution proteometric imaging through array tomography to define features of single synapses in the adult mouse neocortex. We find that glutamatergic synapses cluster into subclasses that parallel the distinct biochemical and functional categories of receptor subunits: GluA1/4, GluA2/3 and GluN1/GluN2B.

Thighplasty for Transfemoral Amputations and Osseointegration: Lower Rate of Complications Than Thighplasty for Body Contouring.

Background: Modern techniques in lower extremity amputation have made significant advances to improve prosthetic control and soft-tissue envelopes through various techniques, including medial thighplasties. These advances are necessary to enhance the fit and functionality of the prosthesis in transfemoral amputations.

Methods: We performed a retrospective review of all thighplasties performed at our institution in patients with ipsilateral transfemoral amputation from November 2017 to December 2021.

Nonoperative management of rectal cancer.

The management of locally advanced rectal cancer has changed drastically in the last few decades due to improved surgical techniques, development of multimodal treatment approaches and the introduction of a watch and wait (WW) strategy. For patients with a complete response to neoadjuvant treatment, WW offers an opportunity to avoid the morbidity associated with total mesorectal excision in favor of organ preservation. Despite growing interest in WW, prospective data on the safety and efficacy of nonoperative management are limited.

Structure guided functional analysis of the S. cerevisiae Mre11 complex.

The Mre11 complex comprises Mre11, Rad50 and Nbs1 (Xrs2 in ). The core components, Mre11 and Rad50 are highly conserved, with readily identifiable orthologs in all clades of life, whereas Nbs1/Xrs2 are present only in eukaryotes. In eukaryotes, the complex is integral to the DNA damage response, acting in DNA double strand break (DSB) detection and repair, and the activation of DNA damage signaling.

Risk Stratification of Uterine Smooth Muscle Tumors: The Role of Morphology, Immunohistochemistry, and Molecular Testing.

Uterine smooth muscle neoplasms are a biologically and clinically heterogeneous group of tumors. Morphology is the cornerstone of pathologic diagnosis of these tumors, and most are readily classified as benign or malignant on the basis of routine histologic examination. However, rare subsets-including intravenous leiomyomatosis, benign metastasizing leiomyoma, and disseminated peritoneal leiomyomatosis-have a capacity for extrauterine spread despite benign cytomorphology.

Nutrition in Advanced Disease and End of Life Cancer Care.

Objectives: This paper addresses nutritional challenges in advanced cancer and at the end of life and implications for oncology nursing practice.

Methods: Recent literature and position statements regarding nutritional support in advanced disease and at the end of life were reviewed and case studies were developed to illustrate the nutritional issues facing patients and family members.

Results: The literature and case examples illustrate the many issues confronting patients, families, and clinicians related to nutritional support including balancing the goals of comfort versus prolonged survival.

Patterns of reconstruction following margin-controlled surgery for melanoma of the lentigo maligna type of the head and neck.

Melanoma of the lentigo maligna (LM) type is most commonly located on the head and neck region. This subtype of melanoma poses surgical challenges due to its location on anatomically sensitive areas and frequent presence of subclinical extension. To analyze the reconstruction patterns of LM patients undergoing margin-controlled surgery.

Preclinical Evaluation of [I]-Sotorasib for the Imaging of Kirsten Rat Sarcoma G12C Mutant Tumors.

Kirsten rat sarcoma (KRAS) is a frequently mutated oncogene responsible for several oncogenic KRAS variants and for driving tumor proliferation. Some nonsmall cell lung cancer (NSCLC) tumors exhibit KRAS G12C mutations, which can be targeted for inhibition using covalent and more recently noncovalent inhibitors. Sotorasib was the first FDA-approved G12C inhibitor that has shown efficacy in lung cancer patients, but with mixed responses.

Challenges and lessons learned in recruiting participants for school-based disease prevention programs during COVID-19.

Schools provide an ideal setting for delivery of disease prevention programs due to the ability to deliver health education and counseling, including health behavior interventions, to large numbers of students. However, the remote and hybrid learning models that arose during the coronavirus (COVID-19) pandemic created obstacles to these efforts. In this article, we provide insights on collaborating with schools to deliver disease prevention programming during the height of the COVID-19 pandemic, and in subsequent years.

Oral self-management of palbociclib using mobile technology: Findings from a nurse-led randomized controlled trial.

Objective: Test the feasibility and effectiveness of a text message reminder intervention for the self-management of oral anticancer medication in patients with metastatic breast cancer.

Methods: Forty-three females initiating treatment with palbociclib participated in a two-armed prospective randomized clinical trial. Participants were randomized into the control ( = 21) and intervention groups ( = 22) from January 2020 to January 2023.

Integrating artificial intelligence in renal cell carcinoma: evaluating ChatGPT's performance in educating patients and trainees.

Background: OpenAI's ChatGPT is a large language model-based artificial intelligence (AI) chatbot that can be used to answer unique, user-generated questions without direct training on specific content. Large language models have significant potential in urologic education. We reviewed the primary data surrounding the use of large language models in urology.

The efficacy of plasma exosomal miRNAs as predictive biomarkers for PD-1 blockade plus chemotherapy in gastric cancer.

Background: The response of gastric cancer (GC) patients to first-line programmed cell death 1 (PD-1) blockade and S-1 plus oxaliplatin (SOX) chemotherapy varies considerably, and the underlying mechanisms driving this variability remain elusive. Exosomal microRNAs (miRNAs or miRs) have emerged as potential biomarkers for efficacy prediction due to their roles in GC biology and stable expression in serum. In this study, we aimed to identify biomarkers to predict patients' response to anti-PD-1 therapy and further elucidate the potential mechanisms by which these exosomal miRNAs modulate the immune response in GC.

Outcomes of definitive radiotherapy vs. laryngectomy followed by adjuvant radiotherapy in patients with locally advanced laryngeal squamous cell carcinoma: real-world experience in a referral cancer center.

Background: Laryngeal cancer is a common head and neck cancer. Surgical treatment can impair patients' voice and swallowing function, making definitive radiotherapy a viable alternative for locally advanced cases.

Methods: To compare the outcomes of definitive versus adjuvant radiotherapy in patients with primary locally advanced laryngeal cancer, we retrospectively evaluated consecutive patients treated from 2007 to 2020.

Engineered extrachromosomal oncogene amplifications promote tumorigenesis.

Focal gene amplifications are among the most common cancer-associated mutations but have proven challenging to engineer in primary cells and model organisms. Here we describe a general strategy to engineer large (more than 1 Mbp) focal amplifications mediated by extrachromosomal DNAs (ecDNAs) in a spatiotemporally controlled manner in cells and in mice. By coupling ecDNA formation with expression of selectable markers, we track the dynamics of ecDNA-containing cells under physiological conditions and in the presence of specific selective pressures.

A Podcast Discussion on the Intracranial Efficacy of Antibody-Drug Conjugates in Patients with EGFR-Mutated NSCLC with Brain Metastases.

The incidence of brain metastases is higher in patients with non-small cell lung cancer (NSCLC) than in patients with most other cancers, and the development of brain metastases is associated with poor prognosis. The objective of the podcast is to provide information about current and future treatments for brain metastases that develop in patients with EGFR-mutated NSCLC. The panel discusses surveillance and management of patients with brain metastases, different types of currently used treatments, and recent data on the intracranial efficacy of antibody-drug conjugates (ADCs).

Prognosis and tumor microenvironment in pseudohypoxic pheochromocytoma/paraganglioma.

Pheochromocytoma and paraganglioma (PPGL) are rare tumors that occur in the adrenal medulla and extra-adrenal tissues, respectively. The prognosis and tumor microenvironment (TME) of pseudohypoxic PPGL as a major entity have not been fully described. Based on the clinical database of 65 patients with PPGL, we assessed the morphological features as well as the immunohistochemistry of pseudohypoxia-related proteins (SDHB and CAIX) and TME-related immune cell markers.

Role of inducible nitric oxide (iNOS) and nitrosative stress in regulating sex differences in secondary lymphedema.

Secondary lymphedema is a common complication following surgical treatment of solid tumors. Although more prevalent in women due to higher breast cancer rates, men also develop lymphedema, often with more severe manifestations. Despite these differences in clinical presentation, the cellular mechanisms underlying sex differences are poorly understood.

Multiome Perturb-seq unlocks scalable discovery of integrated perturbation effects on the transcriptome and epigenome.

Single-cell CRISPR screens link genetic perturbations to transcriptional states, but high-throughput methods connecting these induced changes to their regulatory foundations are limited. Here, we introduce Multiome Perturb-seq, extending single-cell CRISPR screens to simultaneously measure perturbation-induced changes in gene expression and chromatin accessibility. We apply Multiome Perturb-seq in a CRISPRi screen of 13 chromatin remodelers in human RPE-1 cells, achieving efficient assignment of sgRNA identities to single nuclei via an improved method for capturing barcode transcripts from nuclear RNA.

Perspectives of the medical oncologist regarding adjuvant chemotherapy for pancreatic cancer: An international expert survey and case vignette study.

Introduction: Adjuvant chemotherapy improves survival in patients with resected pancreatic ductal adenocarcinoma (PDAC). The decision to initiate chemotherapy involves both patient and physician factors, decision-specific criteria, and contextual considerations. This study aimed to assess medical oncologists' views on adjuvant chemotherapy following pancreatic resection for PDAC.

GLI1::FOXO4-rearranged kidney tumors: a potentially distinct renal subtype within the spectrum of GLI1-altered tumors?

Pathogenic alterations, namely, fusions and amplifications, of the GLI1 gene have been identified in various mesenchymal tumors, including pericytoma with t(7;12), plexiform fibromyxoma, gastroblastoma, and other malignant mesenchymal neoplasms arising in the soft tissues, as well as in various visceral organs. However, only three cases of GLI1-rearranged renal tumors have been reported to date, comprising two low-grade spindle cell tumors with GLI1::FOXO4 fusion along with one GLI1-rearranged case with an unknown fusion partner. In this study, we analyzed three cases with GLI1::FOXO4 fusion and overlapping morphology.

Impact of Power and Time in Hepatic Microwave Ablation: Effect of Different Energy Delivery Schemes.

Microwave ablation often involves the use of continuous energy-delivery protocols with a fixed power and time. To achieve larger ablation zones, a range of protocols and power levels have been studied in experimental studies. The objective of the present study was to develop and experimentally evaluate the performance of a coupled computational electromagnetic-bioheat transfer model of 2.