Trastuzumab Plus Pertuzumab Versus Cetuximab Plus Irinotecan in Patients With Wild-Type, HER2-Positive, Metastatic Colorectal Cancer (S1613): A Randomized Phase II Trial.

Purpose: overexpression/amplification in wild-type (WT) metastatic colorectal cancer (mCRC; human epidermal growth factor receptor 2 [HER2]-positive mCRC) appears to be associated with limited benefit from anti-EGFR antibodies and promising responses to dual-HER2 inhibition; however, comparative efficacy has not been investigated. We conducted a randomized phase II trial to evaluate efficacy and safety of dual-HER2 inhibition against standard-of-care anti-EGFR antibody-based therapy as second/third-line treatment in HER2-positive mCRC.

Methods: Patients with -WT mCRC after central confirmation of HER2 positivity (immunohistochemistry 3+ or 2+ and in situ hybridization amplified [HER2/CEP17 ratio >2.

Osteomyelitis and Septic Arthritis in the Darwin Prospective Melioidosis Study.

Background: Melioidosis is a multisystem infectious disease caused by the environmental bacterium . Osteomyelitis (OM) and septic arthritis (SA) are uncommon primary presentations for melioidosis but important secondary foci, often requiring prolonged therapy and multiple surgeries. We characterized the epidemiology, presentation, treatment, and outcomes of patients from 24 years of the Darwin Prospective Melioidosis Study (DPMS).

Phasic dopamine release in two different rat models of attention-deficit/hyperactivity disorder: Spontaneously hypertensive rats (SHR) versus Lphn3 knockout rats.

We examined DA activity in the medial prefrontal cortex (mPFC) and nucleus accumbens core (NAcc) in two Different Rat Models of Attention-Deficit/Hyperactivity Disorder: Spontaneously Hypertensive Rats (SHR) Versus Lphn3 Knockout Rats. We examined baseline stimulation-evoked phasic DA release, half-life, and DA autoreceptor (DAR) functioning in the mPFC and NAcc, as well as the response to nomifensine (10 mg/kg, IP), a DA transporter (DAT) blocker, on these measures in the NAcc. Both rat models were hypodopaminergic, with notable regional and mechanistic differences.

Four-electron reduction of benzene by a samarium(II)-alkyl without the addition of external reducing agents.

Benzene reduction by molecular complexes remains an important synthetic challenge, requiring harsh reaction conditions involving group I metals. Reductions of benzene, to date, typically result in a loss of aromaticity, although the benzene tetra-anion, a 10π-electron system, has been calculated to be stable and aromatic. Due to the lack of sufficiently potent reductants, four-electron reduction of benzene usually requires the use of group I metals.

Systematic Review of Pain Assessment Measures Used in Pediatric Acute Lymphoblastic Leukemia.

Background: Pain is a prevalent, frequent, and often persistent symptom among children with acute lymphoblastic leukemia (ALL). Despite its high prevalence, pain has remained understudied, and no evidence-based recommendations exist for how best to assess and treat pain in this population. Without proper assessment, clinical efforts to improve pain management in pediatric ALL will be ineffective.

ALK-positive anaplastic large cell lymphoma initially diagnosed as neurosarcoidosis in a 12-year-old girl.

We present a rare case of optic neuropathy due to anaplastic lymphoma kinase-positive (ALK+) anaplastic large cell lymphoma (ALCL) with optic nerve infiltration in a 12-year-old girl who presented with acute unilateral vision loss, diplopia, and headache after two prior hospitalizations at an outside facility for disk edema. She had a presumptive diagnosis of neurosarcoidosis and empiric treatment had been initiated with high-dose corticosteroids. Ongoing worsening of vision prompted presentation at our facility.

Linking Black women to PrEP care using warm handoff referrals from emergency departments to local PrEP clinics.

New Human Immunodeficiency Virus (HIV) cases continue to disproportionately burden cisgender Black/African American women in the United States due to a confluence of structural and systemic factors. Pre-exposure prophylaxis (PrEP) is a safe and effective HIV prevention option, yet there is a striking gap between PrEP eligibility and uptake among cisgender Black women. The current study evaluates a novel warm handoff process in a hospital emergency department setting linking eligible women to local PrEP clinics within 72 hours of hospital discharge in a large southwestern metropolitan city.

Incorporating Economic Evidence in Clinical Guidelines: A Framework From the Clinical Guidelines Committee of the American College of Physicians.

In recognition of accelerating health care spending and alignment with the American College of Physicians (ACP) principles of promoting high-value care, the ACP Clinical Guidelines Committee (CGC) developed a framework to standardize its approach to identifying, appraising, and considering economic evidence in the development of ACP clinical guidelines. This article presents the CGC's process for incorporating economic evidence, which encompasses cost-effectiveness analyses, economic outcomes in randomized controlled trials, and resource utilization (intervention cost) data. Economic evidence is one component of ACP recommendations.

Peer review comments: Friend or foe?

Peer review is a time-honored cornerstone of publishing. Peer reviewers, often blinded to the author, provide feedback to clarify the manuscript and validate the key messages and sciences. Authors may openly accept the feedback outright and make revisions.

Engaging rural communities in Bangladesh to tackle antimicrobial resistance through the Community Dialogue Approach: a process evaluation protocol for COSTAR project in Cumilla, Bangladesh.

Introduction: Antimicrobial resistance (AMR) is a global problem and is especially threatening for low-and-middle income countries like Bangladesh. The COSTAR (Community-led Solutions to Antimicrobial Resistance) project includes a Randomised Control Trial (RCT) which aims to evaluate the effectiveness of the Community Dialog Approach (CDA) to improve levels of correct and appropriate knowledge and reported practice about antibiotics, antibiotic use, and antibiotic resistance (ABR) from a One Health perspective, among adult community members in 5 selected sub-districts of Cumilla. The CDA is a community engagement approach involving community members in active discussions also known as Community Dialogs (CD), run by local facilitators.

Biopreservation and reversal of oxidative injury during blood storage by a novel curcumin-based gel formulation.

Blood storage lesion induces cytosolic and membrane changes driven in part by hemoglobin (Hb) oxidation reactions within red blood cells (RBCs). A novel gel formulation containing the antioxidant curcuminoids in a biocompatible solvent system was used to deliver curcumin into RBCs. Incubation of peroxide treated RBCs stored in PBS with curcumin gel led to a reduction in prooxidant ferrylHb and recovery in ATP.

Interruption of the visual cycle in a novel animal model induces progressive vision loss resembling Stargardts Disease.

Mutations in the gene ABCA4 coding for photoreceptor-specific ATP-binding cassette subfamily A member 4, are responsible for Stargardts Disease type 1 (STGD1), the most common form of inherited macular degeneration. STGD1 typically declares early in life and leads to severe visual handicap. Abca4 gene-deletion mouse models of STGD1 accumulate lipofuscin, a hallmark of the disease, but unlike the human disease show no or only moderate structural changes and no functional decline.

Drug resistant Mycobacterium tuberculosis strains have altered cell envelope hydrophobicity that influences infection outcomes in human macrophages.

In recent decades, drug resistant (DR) strains of Mycobacterium tuberculosis (M.tb), the cause of tuberculosis (TB), have emerged that threaten public health. Although M.

Identification and Confirmation of Virulence Factor Production from , a Causal Agent of Root Rot in Pulses.

is an aggressive pathogen of pulse crops and a causal agent in root rot disease that negatively impacts Canadian agriculture. This study reports the results of a targeted metabolomics-based profiling of secondary metabolism in an 18-strain panel of cultured axenically in multiple media conditions, in addition to an in planta infection assay involving four strains inoculated on two pea cultivars. Multiple secondary metabolites with known roles as virulence factors were detected which have not been previously associated with , including fungal decalin-containing diterpenoid pyrones (FDDPs), fusaoctaxins, sambutoxin and fusahexin, in addition to confirmation of previously reported secondary metabolites including enniatins, fusarins, chlamydosporols, JM-47 and others.

Embed systemic equity throughout industrial ecology applications: How to address machine learning unfairness and bias.

Recent calls have been made for equity tools and frameworks to be integrated throughout the research and design life cycle -from conception to implementation-with an emphasis on reducing inequity in artificial intelligence (AI) and machine learning (ML) applications. Simply stating that equity should be integrated throughout, however, leaves much to be desired as industrial ecology (IE) researchers, practitioners, and decision-makers attempt to employ equitable practices. In this forum piece, we use a critical review approach to explain how socioecological inequities emerge in ML applications across their life cycle stages by leveraging the food system.

High Detection Rates for Prostate-specific Membrane Antigen-avid Prostate Cancer Recurrence at Low Prostate-specific Antigen levels on Extended Axial Field-of-view Positron Emission Tomography/Computed Tomography.

Background And Objective: Although prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has impacted the investigation and management of biochemical recurrence (BCR) of prostate cancer, negative scans are common at low rising prostate-specific antigen (PSA) levels. PET/CT devices with an extended axial field-of-view, such as the Siemens Biograph Vision Quadra (Quadra) scanner, have substantially higher sensitivity than conventional field-of-view scanners. Our aim was to assess whether the enhanced signal-to-noise ratios achieved on the Quadra scanner improve detection of low-volume disease and thereby increase detection of PC at low PSA levels.

Validation and Final Results from the First Cardiac Lead Post-Approval Study Using Real-World Data.

Background: As part of Electrophysiology Predictable and Sustainable Implementation of National Registries (EP PASSION), a multi-stakeholder collaboration between the US Food and Drug Administration (FDA), academic and society partners, and cardiovascular implantable electronic device manufacturers, a 5-year bradycardia lead study transitioned from a traditional post-approval study (PAS) to a real-world data (RWD) approach using a novel method to evaluate chronic cardiac lead complications.

Methods: Lead complications were identified using a combination of diagnosis and procedure codes from 2013 to 2020 fee-for-service Medicare claims data along with BIOTRONIK device registration and Medical Device Reporting data from patients implanted between 2013 and 2015 with a Solia S lead. A proof-of-concept analysis was performed using McNemar's test to compare lead complications reported in the traditional PAS with lead complications identified in the RWD.

Equipping a Wyatt multiangle, multidetector instrument for real-time particle and polymer sizing by simultaneous multiple-angle dynamic and static light scattering.

Well-constructed instruments may continue to perform beyond their manufacturer-supported service lifetime, which is typically limited by computer operating system compatibility or the availability of spare parts. Often, such equipment is condemned to surplus and destroyed. End-of-life plans that retain some of the material and energy used to create scientific instruments are of interest, just as in other manufacturing sectors.

Fenestrated and Branched Endovascular Aortic Repair and Mortality at Hospitals Without Investigational Device Trials.

Importance: Fenestrated and branched endovascular aortic repairs (F/BEVAR) have been adopted by many centers. However, national trends of F/BEVAR use remain unclear, particularly at sites who perform them without an US Food and Drug Adminstration (FDA)-approved investigational device exemption (IDE).

Objective: To quantify the use of F/BEVAR in the US and to determine if mortality was different at IDE vs non-IDE sites.

CoREST Complex Inhibition Alters RNA Splicing to Promote Neoantigen Expression and Enhance Tumor Immunity.

Unlabelled: Epigenetic complexes tightly regulate gene expression and colocalize with RNA splicing machinery; however, the consequences of these interactions are uncertain. Here, we identify unique interactions of the CoREST repressor complex with RNA splicing factors and their functional consequences in tumorigenesis. Using mass spectrometry, in vivo binding assays, and cryo-EM we find that CoREST complex-splicing factor interactions are direct and perturbed by the CoREST complex inhibitor, corin, leading to extensive changes in RNA splicing in melanoma and other malignancies.

Annotating publicly-available samples and studies using interpretable modeling of unstructured metadata.

Reusing massive collections of publicly available biomedical data can significantly impact knowledge discovery. However, these public samples and studies are typically described using unstructured plain text, hindering the findability and further reuse of the data. To combat this problem, we propose txt2onto 2.

Effectiveness of dolutegravir-based regimens compared to raltegravir-, elvitegravir-, bictegravir, and darunavir-based regimens among older adults with HIV in the Veterans Aging Cohort Study (VACS).

Background: Real-world data on treatment patterns and clinical outcomes for newer drugs, including integrase strand transfer inhibitors, among older people with human immunodeficiency virus (PWH) are limited.

Methods: This cohort study included PWH enrolled in the Veterans Aging Cohort Study (VACS) who were prescribed a standard 3-drug antiretroviral therapy (ART) regimen containing dolutegravir (DTG), bictegravir (BIC), cobicistat boosted elvitegravir (EVG), raltegravir (RAL), or darunavir/ritonavir (DRV) plus 2 nucleoside reverse transcriptase inhibitors between January 1, 2014, and March 31, 2020, and who were ≥50 years at regimen initiation. The association between regimen and virologic effectiveness or discontinuation was assessed using logistic regression models with inverse probability of treatment weights.

Leveraging local public health to advance antimicrobial stewardship (AMS) implementation and mitigate antimicrobial resistance (AMR): a scoping review.

Objective: To explore the role of local public health organisations in antimicrobial stewardship (AMS) and antimicrobial resistance (AMR) surveillance.

Methods: A scoping review was conducted. Peer-reviewed and grey literature from countries within the organisation for economic co-operation and development was searched between 1999 and 2023 using the concepts of local public health, AMR and AMS.

Health systems responsiveness towards needs of pregnant women in Vietnam.

Background: Health systems that are responsive to maternal mental health recognise the importance of integrating mental health services into maternal care. Studies from Vietnam have reported particularly high rates of common perinatal mental health disorders (CPMDs) in both rural and urban areas of the country. Despite the increasing burden of maternal mental health conditions, there is currently no guidance on the screening for CPMDs within maternal care, both antenatal and postnatal.

ERBB2/HOXB13 co-amplification with interstitial loss of BRCA1 defines a unique subset of breast cancers.

Background: The HOXB13/IL17RB gene expression biomarker has been shown to predict response to adjuvant and extended endocrine therapy in patients with early-stage ER+ HER2- breast tumors. HOXB13 gene expression is the primary determinant driving the prognostic and endocrine treatment-predictive performance of the biomarker. Currently, there is limited data on HOXB13 expression in HER2+ and ER- breast cancers.