The efficacy and safety of rhGH treatment combined with letrozole/GnRHa in adolescent boys.

Objective: In boys during puberty who were undergoing recombinant human growth hormone (rhGH) treatment, we compared the therapeutic efficacy on growth, and any adverse reactions, of co-therapy with either letrozole or gonadotropin-releasing hormone analog (GnRHa).

Methods: Fifty-six pubertal growth hormone deficiency (GHD) boys were studied, they were treated with the combination of letrozole and rhGH (letrozole group, n = 28) or the combination of GnRHa and rhGH (GnRHa group, n = 28) for at least one year. Eighteen patients in the letrozole group and seventeen patients in the GnRHa group attained final adult height (FAH).

Retrospective Evaluation of Novel Synthetic Opioids and Xylazine Chronic Intake by Post-Mortem Hair Testing.

Fentanyl and its derivatives (nonpharmaceutical fentanyl, NPFs) represent the largest group among synthetic opioids. Fentanyl-related deaths and fatalities from tampering with pharmaceutical products have been reported. Furthermore, in the United States, adulterants such as xylazine and other substances, including the nitazenes class of opioids, have been found in an increasing number of unintentional overdose deaths, drug seizures, and reports of use by recreational drug users.

PET imaging of Mn labeled DOTATATE and DOTAJR11.

Manganese-52 is gaining interest as an isotope for PET imaging due to its desirable decay and chemical properties for radiopharmaceutical development. Somatostatin receptor 2 (SSTR2) is significantly overexpressed by neuroendocrine tumors (NETs) and is an important target for nuclear imaging and therapy. As an agonist, [Ga]Ga-DOTATATE has demonstrated significant internalization upon interaction with receptor ligands, whereas [Ga]Ga-DOTA-JR11(as an antagonist) exhibits limited internalization but better pharmacokinetics and increased tumor uptake.

Impact of early initiation of renal replacement therapy in patients on venoarterial ECMO using target trial emulation with Japanese nationwide data.

While renal replacement therapy (RRT) allows for precise fluid management as well as addressing electrolyte imbalances and the removal of other necessary compounds, its early initiation has not shown benefit in the general critically ill population. Moreover, the effects of early RRT initiation specifically in patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO) also remain unclear. This retrospective study investigated adult patients who underwent VA-ECMO between April 2018 and March 2022 and used the clone-censor-weight method to emulate a hypothetical target trial and compare two groups: patients who initiated RRT within 2 days of VA-ECMO initiation (Early) and those who did not (Late).

Dysregulated miRNA Expression and Androgen Receptor Loss in Racially Distinct Triple-Negative Breast Cancer.

Androgen receptor (AR)-negative triple-negative breast cancer (TNBC), often termed quadruple-negative breast cancer (QNBC), disproportionately impacts women of African descent, leading to poorer overall survival (OS). MiRNAs regulate the expression of gene drivers involved in critical signaling pathways in TNBC, such as the gene, and their expression varies across races and breast cancer subtypes. This study investigates whether differentially expressed miRNAs influence AR transcription, potentially contributing to the observed disparities between African American (AA) and European American (EA) QNBC patients.

Late-Life Alcohol Exposure Does Not Exacerbate Age-Dependent Reductions in Mouse Spatial Memory and Brain TFEB Activity.

Alcohol consumption is believed to affect Alzheimer's disease (AD) risk, but the contributing mechanisms are not well understood. A potential mediator of the proposed alcohol-AD connection is autophagy, a degradation pathway that maintains organelle and protein homeostasis. Autophagy is regulated through the activity of Transcription factor EB (TFEB), which promotes lysosome and autophagy-related gene expression.

Mechanism of enhancing chemotherapy efficacy in pancreatic ductal adenocarcinoma with paricalcitol and hydroxychloroquine.

Pancreatic ductal adenocarcinoma (PDAC) has a minimal (<15%) 5-year existence, in part due to resistance to chemoradiotherapy. Previous research reveals the impact of paricalcitol (P) and hydroxychloroquine (H) on altering the lysosomal fusion, decreasing stromal burden, and triggering PDAC to chemotherapies. This investigation aims to elucidate the molecular properties of the H and P combination and their potential in sensitizing PDAC to gemcitabine (G).

Changes in Medication Complexity and Post-Hospitalization Outcomes in Older Adults Hospitalized for Heart Failure.

Introduction: Medication regimen complexity may be an important risk factor for adverse outcomes in older adults with heart failure. However, increasing complexity is often necessary when prescribing guideline-directed medical therapy at the time of a heart failure hospitalization. We sought to determine whether increased medication regimen complexity following a heart failure hospitalization was associated with worse post-hospitalization outcomes.

New Sesterterpenes from the Antarctic Sponge sp.

Chemical investigation of the Antarctic sponge sp. has previously led to the identification of new suberitane derivatives, some of which show bioactivity toward respiratory syncytial virus (RSV). Our ongoing NMR-guided investigation of new specimens of the sponge resulted in the isolation of five new analogs (-), previously reported suberitenones A-D (-), and oxaspirosuberitenone ().

International workshop: what is needed to ensure outcome measures for Rett syndrome are fit-for-purpose for clinical trials? June 7, 2023, Nashville, USA.

Introduction: The clinical, research and advocacy communities for Rett syndrome are striving to achieve clinical trial readiness, including having fit-for-purpose clinical outcome assessments. This study aimed to (1) describe psychometric properties of clinical outcome assessment for Rett syndrome and (2) identify what is needed to ensure that fit-for-purpose clinical outcome assessments are available for clinical trials.

Methods: Clinical outcome assessments for the top 10 priority domains identified in the Voice of the Patient Report for Rett syndrome were compiled and available psychometric data were extracted.

Advancements in Immunity and Dementia Research: Highlights from the 2023 AAIC Advancements: Immunity Conference.

The immune system is a key player in the onset and progression of neurodegenerative disorders. While brain resident immune cell-mediated neuroinflammation and peripheral immune cell (eg, T cell) infiltration into the brain have been shown to significantly contribute to Alzheimer's disease (AD) pathology, the nature and extent of immune responses in the brain in the context of AD and related dementias (ADRD) remain unclear. Furthermore, the roles of the peripheral immune system in driving ADRD pathology remain incompletely elucidated.

Human placental stem cell-based therapies for prevention of abdominal adhesions: A prospective randomized preclinical trial.

Background: Abdominal adhesions are networks of fibrotic tissues that form between organs postoperatively. Current prophylactic strategies do not reproducibly prevent adhesive small bowel obstruction across the entire abdomen. Human placental-derived stem cells produce an anti-inflammatory secretome that has been applied to multiple fibrosing diseases.

S-PLM: Structure-Aware Protein Language Model via Contrastive Learning Between Sequence and Structure.

Proteins play an essential role in various biological and engineering processes. Large protein language models (PLMs) present excellent potential to reshape protein research by accelerating the determination of protein functions and the design of proteins with the desired functions. The prediction and design capacity of PLMs relies on the representation gained from the protein sequences.

Impact of syndemic heavy drinking, smoking, and depression on mortality among MSM with and without HIV: A longitudinal study.

Background: Heavy drinking, smoking, and depression are common among men who have sex with men (MSM). The association of co-occurring longitudinal patterns of these conditions and mortality among MSM were tested, applying a syndemic framework - the interaction of two or more conditions that contribute to poor health outcomes.

Methods: Longitudinal data from 1999 to 2018 from the Multicenter AIDS Cohort Study of 3046 MSM were analyzed.

Multicenter Clinical Performance Evaluation of the NeuMoDx™ CT/NG Assay 2.0.

Background: Given the continued increases in rates of both Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection, additional diagnostic assays may be useful in increasing access to testing for these sexually transmitted infections. We evaluated the performance of the NeuMoDx™ CT/NG Assay 2.0 on the NeuMoDx-96 and NeuMoDx-288 Molecular Systems.

Associations between life-course FEV/FVC trajectories and respiratory symptoms up to middle age: analysis of data from two prospective cohort studies.

Background: Life-course lung function trajectories leading to airflow obstruction, as measured by impaired FEV/FVC (forced vital capacity), precede the onset of chronic obstructive pulmonary disease (COPD). We aimed to investigate whether individuals on impaired FEV/FVC trajectories have an increased burden of respiratory symptoms, including those who do not meet the spirometric criteria for COPD.

Methods: We analysed serial life-course data from two population-based cohort studies separately, which included respiratory symptoms and spirometry: the Tasmanian Longitudinal Health Study (TAHS, Australia) cohort was recruited at age 6-7 years and followed up until middle age (mean age 53 years; range 51-55); and the Coronary Artery Risk Development in Young Adults (CARDIA, USA) cohort was recruited at a mean age of 25 years (range 18-30) and followed up to a mean age of 55 years (range 47-64).

Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons.

Background: Twice-yearly subcutaneous lenacapavir has been shown to be efficacious for prevention of HIV infection in cisgender women. The efficacy of lenacapavir for preexposure prophylaxis (PrEP) in cisgender men, transgender women, transgender men, and gender-nonbinary persons is unclear.

Methods: In this phase 3, double-blind, randomized, active-controlled trial, we randomly assigned participants in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF).

Multilevel Resilience and Appointment Attendance Among African American/Black Adults with HIV: A Prospective Multisite Cohort Study.

Background: Attending clinic appointments supports HIV viral suppression, yet racial disparities are documented. We assessed whether multilevel resilience resources were associated with appointment attendance among African American/Black (AA/B) adults living with HIV in the United States.

Methods: We ascertained data from 291 AA/B clinical cohort participants from 2018 to 2021.

A qualitative exploration of the client-provider relationship and its role in discussing sexual health and HIV among African American women in the US South.

Objective: Sexually transmitted infections (STIs), including HIV, are a key contributor to psychological and physical morbidity across the United States (US). African American (AA) women are disproportionately impacted by STIs, particularly in the Deep South of the US. Strong patient-provider communication can help to increase client understanding of STI prevention and treatment options.

Performance of an AI-powered visualization software platform for precision surgery in breast cancer patients.

Surgery remains the primary treatment modality in the management of early-stage invasive breast cancer. Artificial intelligence (AI)-powered visualization platforms offer the compelling potential to aid surgeons in evaluating the tumor's location and morphology within the breast and accordingly optimize their surgical approach. We sought to validate an AI platform that employs dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to render three-dimensional (3D) representations of the tumor and 5 additional chest tissues, offering clear visualizations as well as functionalities for quantifying tumor morphology, tumor-to-landmark structure distances, excision volumes, and approximate surgical margins.

Development and validation of clinical criteria to identify familial chylomicronemia syndrome (FCS) in North America.

Background: Familial chylomicronemia syndrome (FCS) is an ultrarare inherited disorder. Genetic testing is not always feasible or conclusive. European clinicians developed a "FCS score" to differentiate between FCS and multifactorial chylomicronemia syndrome (MCS), a more common condition with overlapping features.