Extracellular vesicles: essential agents in critical bone defect repair and therapeutic enhancement.

Bone serves as a fundamental structural component in the body, playing pivotal roles in support, protection, mineral supply, and hormonal regulation. However, critical-sized bone injuries have become increasingly prevalent, necessitating extensive medical interventions due to limitations in the body's capacity for self-repair. Traditional approaches, such as autografts, allografts, and xenografts, have yielded unsatisfactory results.

Defining the Optimal Dose for 3-Dimensional Conformal Accelerated Partial Breast Irradiation: 15-Year Follow-Up of a Dose-Escalation Trial.

Purpose: Randomized trials have demonstrated similar local tumor control in patients treated with accelerated partial-breast irradiation (APBI) compared with whole-breast irradiation. However, the optimal APBI dose for maximizing tumor control and minimizing toxicity is uncertain.

Methods And Materials: We enrolled patients ≥18 years of age with grade 1 or 2 ductal carcinoma in situ or stage I invasive breast cancer and resection margins ≥2 mm between 2003 and 2011 to a sequential dose-escalation trial using 3-dimensional conformal external beam APBI giving twice daily 4 Gy fractions with total doses of 32 Gy, 36 Gy, and 40 Gy.

The Society of Thoracic Surgeons (STS) Clinical Practice Guideline on Surgical Management of Oligometastatic Non-small Cell Lung Cancer.

Background: The use of local consolidative therapy (LCT) in patients with oligometastatic non-small cell lung cancer (NSCLC) is rapidly evolving, with a preponderance of data supporting the benefits of such therapeutic approaches incorporating pulmonary resection for appropriately selected candidates. However, practices vary widely institutionally and regionally, and evidence-based guidelines are lacking.

Methods: The Society of Thoracic Surgeons assembled a panel of thoracic surgical oncologists to evaluate and synthesize the available evidence regarding the role of pulmonary resection as LCT.

Evidence for intrinsic DNA dynamics and deformability in damage sensing by the Rad4/XPC nucleotide excision repair complex.

Altered DNA dynamics at lesion sites are implicated in how DNA repair proteins sense damage within genomic DNA. Using laser temperature-jump (T-jump) spectroscopy combined with cytosine-analog Förster Resonance Energy Transfer (FRET) probes that sense local DNA conformations, we measured the intrinsic dynamics of DNA containing 3 base-pair mismatches recognized in vitro by Rad4 (yeast ortholog of XPC). Rad4/XPC recognizes diverse lesions from environmental mutagens and initiates nucleotide excision repair.

Activation of δ-opioid receptors blocks allodynia in a model of headache induced by PACAP.

Background And Purpose: Pituitary adenylate cyclase activating polypeptide (PACAP) is a human migraine trigger that is being targeted for migraine. The δ-opioid receptor (δ-receptor) is a novel target for the treatment of migraine, but its mechanism remains unclear. The goals of this study were to develop a mouse PACAP-headache model using clinically significant doses of PACAP; determine the effects of δ-receptor activation in this model; and investigate the co-expression of δ-receptors, PACAP and PACAP-PAC1 receptor.

Cell Membrane Fatty Acids and PIPs Modulate the Etiology of Pancreatic Cancer by Regulating AKT.

Pancreatic ductal adenocarcinoma (PDAC) is one of the worst solid malignancies in regard to outcomes and metabolic dysfunction leading to cachexia. It is alarming that PDAC incidence rates continue to increase and warrant the need for innovative approaches to combat this disease. Due to its relatively slow progression (10-20 years), prevention strategies represent an effective means to improve outcomes.

Engineered GM-CSF polarizes protumorigenic tumor-associated macrophages to an antitumorigenic phenotype and potently synergizes with IL-12 immunotherapy.

Background: The use of immune checkpoint inhibitors (CPIs) has become a dominant regimen in modern cancer therapy, however immune resistance induced by tumor-associated macrophages (TAMs) with immune suppressive and evasion properties limits responses. Therefore, the rational design of immune modulators that can control the immune suppressive properties of TAMs and polarize them, as well as dendritic cells (DCs), toward a more proinflammatory phenotype is a principal objective in cancer immunotherapy.

Methods: Here, using a protein engineering approach to enhance cytokine residence in the tumor microenvironment, we examined combined stimulation of the myeloid compartment via tumor stroma-binding granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance responses in both DCs and T cells via stroma-binding interleukin-12 (IL-12).

Chronic rhinosinusitis with nasal polyps: Key considerations in the multidisciplinary team approach.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a recurrent inflammatory disease associated with several comorbidities and a significant disease burden for patients. Treatments include corticosteroids and sinonasal surgery, but these can be associated with the risk of adverse events and nasal polyp recurrence. Biologic treatments such as mepolizumab can be used as an add-on treatment and are effective at reducing surgery and corticosteroid use.

Ethnic enclaves, neighborhood socioeconomic status, and obesity among Hispanic women in Chicago: a latent profile analysis approach.

Purpose: The prevalence of obesity, a crucial risk factor for breast cancer, is markedly higher among Hispanic women. The interaction between ethnic enclaves and neighborhood socioeconomic status (SES) as a determinant of this disparity warrants further research. We aimed to identify neighborhood profiles based on ethnic enclaves and socioeconomic status to evaluate the association with obesity among Hispanic women in the metropolitan Chicago region.

Five principles to prioritise in small-scale surgical quality improvement: a qualitative study of the views of surgical improvement leaders.

Objective: Variations in the quality and safety of surgical care remain persistent. Efforts to improve are needed, but are themselves variably effective, with often disappointing impacts. When compared with large-scale, multisite and better resourced improvement efforts, the evidence base for small-scale quality improvement (QI) has remained under-developed and lacking in clarity on good practice.

ESRP2-microRNA-122 axis promotes the postnatal onset of liver polyploidization and maturation.

Hepatocyte polyploidy and maturity are critical to acquiring specialized liver functions. Multiple intracellular and extracellular factors influence ploidy, but how they cooperate temporally to steer liver polyploidization and maturation or how post-transcriptional mechanisms integrate into these paradigms is unknown. Here, we identified an important regulatory hierarchy in which postnatal activation of epithelial splicing regulatory protein 2 (ESRP2) stimulates processing of liver-specific microRNA () to facilitate polyploidization, maturation, and functional competence of hepatocytes.

Alcohol dehydrogenase 1 acts as a scaffold protein in mitophagy essential for fungal pathogen adaptation to hypoxic niches within hosts.

Fungi have evolved diverse physiological adaptations to hypoxic environments. However, the mechanisms mediating such adaptations remain obscure for many filamentous pathogenic fungi. Here, we show that autophagy mediated mitophagy occurs in the insect pathogenic fungus Beauveria bassiana under hypoxic conditions induced by host cellular immune responses.

Point-of-care ultrasound in Gastroenterology and Hepatology.

Point-of-care ultrasound (POCUS) is changing the practice of nearly all specialties and is increasingly being incorporated as a bedside tool by more gastroenterologists and hepatologists. POCUS is most often used to answer focused clinical questions, supplement the traditional physical examination, and guide performance of invasive bedside procedures. This review describes several common POCUS applications used in gastroenterology and hepatology, as well as some novel applications that warrant further investigation.

Orthopedic Resident Intern Foundations: A Cross-Institutional, Month-Long Skills Training Boot Camp for PGY-1 Residents.

Objective: Orthopedic residents are tasked with rapidly acquiring clinical and surgical skills, especially during their PGY-1 year. However, resource constraints and other factors frequently cause skills training to fall short of established guidelines. We aimed to design and evaluate a cross-institutional, month-long curriculum aimed at pooling resources to optimize training.

Evidence for a metal-bosonic insulator-superconductor transition in compressed sulfur.

The abrupt drop of resistance to zero at a critical temperature is a key signature of the current paradigm of the metal-superconductor transition. However, the emergence of an intermediate bosonic insulating state characterized by a resistance peak preceding the onset of the superconducting transition has challenged this traditional understanding. Notably, this phenomenon has been predominantly observed in disordered or chemically doped low-dimensional systems, raising intriguing questions about the generality of the effect and its underlying fundamental physics.

The impact of lower thoracic versus upper lumbar upper instrumented vertebra in minimally invasive correction of adult spinal deformity.

Objective: The goal of this study was to compare the impact of using a lower thoracic (LT) versus upper lumbar (UL) level as the upper instrumented vertebra (UIV) on clinical and radiographic outcomes following minimally invasive surgery for adult spinal deformity.

Methods: A multicenter retrospective study design was used. Inclusion criteria were age ≥ 18 years, and one of the following: coronal Cobb angle > 20°, sagittal vertical axis > 50 mm, pelvic tilt > 20°, pelvic incidence-lumbar lordosis mismatch > 10°.

The Association of Modified 5-Item Frailty Index on Perioperative Cochlear Implant Speech Perception.

Objective: This study aims to evaluate the potential association of perioperative hearing outcomes with frailty by Modified 5-Item Frailty Index (mFI-5).

Design: Retrospective cross-sectional study.

Setting: Single-institutional study conducted at a tertiary care hospital between January 2018 and January 2022.

ADELLE: A global testing method for trans-eQTL mapping.

Understanding the genetic regulatory mechanisms of gene expression is an ongoing challenge. Genetic variants that are associated with expression levels are readily identified when they are proximal to the gene (i.e.

Epcoritamab plus GemOx in transplant-ineligible relapsed/refractory DLBCL: results from the EPCORE NHL-2 trial.

Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have poor outcomes. Gemcitabine + oxaliplatin (GemOx) with rituximab, a standard salvage therapy, yields complete response (CR) rates of approximately 30% and median overall survival (OS) of 10-13 months. Patients with refractory disease fare worse, with a CR rate of 7% for subsequent therapies and median OS of 6 months.

Intraoperative Application of Ultrasonic Energy to Bioabsorbable Craniosynostosis Fixation Devices and Adverse Tissue Reaction. Is There a Correlation?

Bioabsorbable internal fixation is a well-accepted modality that is especially suitable for application in craniosynostosis. When first introduced, high rates of adverse tissue reactions were observed that have since been ameliorated with more biocompatible polymer formulations. However, the phenomenon has not entirely disappeared, and such reactions remain vexing.

Things Latinas need to plan for safety: A dual-site concept mapping study.

Background: Latina women in the United States experience intimate partner violence (IPV) at high rates, but evidence suggests Latinas seek help for IPV at lower rates than other communities. Safety planning is an approach that provides those experiencing IPV with concrete actions to increase their safety and referrals to formal services. While safety planning is shown to reduce future incidences of violence, little is known about the safety planning priorities of Latinas.

Extracorporeal Membrane Oxygenation in Children with Pulmonary Atresia and Intact Ventricular Septum: Mortality and Associated Outcomes.

Data on outcomes of extracorporeal membrane oxygenation (ECMO) are limited in patients with pulmonary atresia intact ventricular septum (PAIVS). The objective of this study was to describe the use of ECMO and the associated outcomes in patients with PAIVS. We retrospectively reviewed neonates with PAIVS who received ECMO between 2009 and 2019 in 19 US hospitals affiliated with the Collaborative Research for the Pediatric Cardiac Intensive Care Society (CoRe-PCICS).

Journey of PROTAC: From Bench to Clinical Trial and Beyond.

Proteolysis-targeting chimeras (PROTACs) represent a transformative advancement in drug discovery, offering a method to degrade specific intracellular proteins. Unlike traditional inhibitors, PROTACs are bifunctional molecules that target proteins for elimination, enabling the potential treatment of previously "undruggable" proteins. This concept, pioneered by Crews and his team, introduced the use of small molecules to link a target protein to an E3 ubiquitin ligase, inducing ubiquitination and subsequent degradation of the target protein.