and mRNA expression-based risk stratification of acute Myeloid Leukemia.

Prognostication of acute myeloid leukemia (AML) at initial diagnosis relies on identification of pre-determined underlying genetic abnormalities. Nevertheless, the disease course of AML remains highly unpredictable and robust reliable prognostic biomarkers for newly diagnosed AML are lacking. We retrospectively explored two publicly available AML RNA-Seq datasets and found that inferior overall survival was associated with high- and low- transcript levels (" / ") compared to low- and high- transcript levels (" / ") in adult AML patients, with a hazard ratio for death of at least 2.

A Phase II Trial of Onapristone and Fulvestrant for Patients With ER+ and HER2- Metastatic Breast Cancer.

Background: The SMILE study is a multi-institutional phase II clinical trial to determine the efficacy and safety of an antiprogestin, onapristone, in combination with fulvestrant as second-line therapy for patients with ER+, PgR+/-, HER2- metastatic breast cancer. This study was terminated early and herein, we report patient characteristics, and outcomes.

Methods: Eligibility criteria included disease progression on ≥2 lines of prior therapy, ECOG performance status ≤ 2, measurable disease per RECIST 1.

The role of community pharmacists in point-of-care testing and treatment for influenza and Group A Streptococcus -a narrative review using Ecological Systems Theory.

Background: Point-of-care testing (POCT) is a valuable diagnostic approach for identifying pathogens such as Group A Streptococcus (GAS) and influenza. Early detection through POCT allows for timely initiation of appropriate treatments improving public health outcomes and minimizing antibiotic misuse. Community pharmacists are well positioned to offer POCT and treatment, but they face significant system level barriers to widespread implementation and reach.

The associations between cardiovascular and pain responses to a cold pressor test differ between males and females.

Nociceptors contribute to the cardiovascular responses during a cold pressor test (CPT). While these responses are lower in females, data suggest that they perceive the CPT as more painful. Thus, we examined sex differences in associations between pain and cardiovascular responses to a CPT (Aim 1) as well as differences between females using (OC), and not using (NC), an oral contraceptive (Aim 2).

Targeting transforming growth factor-β1 by methylseleninic acid/seleno-L-methionine in clear cell renal cell carcinoma: Mechanisms and therapeutic potential.

Clear cell renal cell carcinoma (ccRCC) poses a significant global health challenge as its incidence continues to rise, resulting in a substantial annual mortality rate. Major clinical challenges to current ccRCC treatments include high drug-resistance rates as well as dose-limiting adverse events; underlining the need to identify additional 'druggable' targets. TGF-β1, VEGF, and PD-L1 are potential therapeutic targets in ccRCC.

RetinaRegNet: A zero-shot approach for retinal image registration.

Retinal image registration is essential for monitoring eye diseases and planning treatments, yet it remains challenging due to large deformations, minimal overlap, and varying image quality. To address these challenges, we propose RetinaRegNet, a multi-stage image registration model with zero-shot generalizability across multiple retinal imaging modalities. RetinaRegNet begins by extracting image features using a pretrained latent diffusion model.

Attitudes, beliefs and preferences surrounding home-based exercise programs in endometrial cancer patients receiving treatment.

Background: Despite recommendations, exercise participation among endometrial cancer survivors remains low. Previous interventions focused on weight loss or in-person programs with limited reach. Regular exercise, regardless of weight change, reduces mortality risk and improves functionality.

Impact of driver licensing renewal policies on older driver crash involvement and injury rates in 13 states, 2000-2019.

Background: Motor vehicle crashes are the second leading cause of injury death among adults aged 65 and older in the U.S., second only to falls.

Mitochondrial Complex I and ROS control synapse function through opposing pre- and postsynaptic mechanisms.

Neurons require high amounts energy, and mitochondria help to fulfill this requirement. Dysfunctional mitochondria trigger problems in various neuronal tasks. Using the neuromuscular junction (NMJ) as a model synapse, we previously reported that Mitochondrial Complex I (MCI) subunits were required for maintaining NMJ function and growth.

Nerve Growth Factor Signaling Tunes Axon Maintenance Protein Abundance and Kinetics of Wallerian Degeneration.

Neurotrophic factors are critical for establishing functional connectivity in the nervous system and sustaining neuronal survival through adulthood. As the first neurotrophic factor purified, nerve growth factor (NGF) is extensively studied for its prolific role in axon outgrowth, pruning, and survival. Applying NGF to diseased neuronal tissue is an exciting therapeutic option and understanding how NGF regulates local axon susceptibility to pathological degeneration is critical for exploiting its full potential.

Discovery and mechanism of a highly selective, antifungal acetyl CoA synthetase inhibitor.

Acetyl CoA synthetases (ACS) have emerged as drug targets for the treatment of cancer, metabolic diseases as well as fungal and parasitic infections. Although a variety of small molecule ACS inhibitors have been discovered, the systematic optimization of these molecules has been slowed by a lack of structural information regarding their mechanism of inhibition. Through a chemical genetic-based, synthetic lethal screen of the human fungal pathogen , we identified an isoxazole-based ACS inhibitor with antifungal activity and exquisite selectivity for the Acs1 relative to human ACSS2 as well as other fungal ACSs.

CFTR mutation is associated with bone differentiation abnormalities in cystic fibrosis.

Background: Cystic Fibrosis-related Bone Disease is an emerging challenge faced by 50 % of adult people with cystic fibrosis (CF). The multifactorial causes of this comorbidity remain elusive. However, congenital bone defects have been observed in animal models with CFTR mutations, suggesting its importance.

Potentiating the effect of immunotherapy in pancreatic cancer using gas-entrapping materials.

Immune checkpoint inhibitors (ICIs) show limited success in treating pancreatic ductal adenocarcinoma (PDAC), largely due to immune evasion mechanisms, including downregulating expression of major histocompatibility complex class I (MHC-I). Our retrospective analysis demonstrated that smoking - a state of elevated CO exposure - is correlated with increased MHC I expression in pancreatic tumors. Here we tested our hypothesis that introducing exogenous CO augments the anti-cancer effects of immunotherapy.

Clinical Advances in the Diagnosis and Treatment of Cerebrovascular Diseases.

The management of cerebrovascular diseases has significantly evolved over the last decade or so [...

The Impact of Cell-Intrinsic STAT6 Protein on Donor T Cell-Mediated Graft-Versus-Tumor Effect.

Bone marrow transplantation (BMT) is mainly performed to restore an anti-tumor immune response, called the graft-versus-tumor (GVT) effect, against leukemia, myeloma and lymphoma. This GVT reactivity is driven by donor T cells, and it can also cause lethal graft-versus-host disease (GVHD). We previously demonstrated that the colonization of mice with helminths preserves the GVT response while suppressing GVHD.

Divergent evolution of a thermospermine-dependent regulatory pathway in land plants.

Plants adapted to life on land by developing diverse anatomical features across lineages. The molecular basis of these innovations often involves the emergence of new genes or establishing new connections between conserved elements, though evidence for evolutionary genetic circuit rewiring remains scarce. Here, we show that the thermospermine-dependent pathway regulating vascular cell proliferation in Arabidopsis thaliana operates as two distinct modules with different functions in the bryophyte Marchantia polymorpha.

Cancer-related health behaviors during the COVID 19 pandemic in geographically diverse samples across the US.

Background: The COVID-19 pandemic involved business closures (e.g., gyms), social distancing policies, and prolonged stressful situations that may have impacted engagement in health behaviors.

EWSR1::BEND2 Adenocarcinoma with Hyaline Pseudorosettes of the Trachea.

We describe the novel occurrence of a adenocarcinoma involving the trachea, with distinct solid and glandular components, in a 34-year-old patient. We illustrate its morphological and immunophenotypic features and describe the molecular finding of an EWSR1::BEND2 gene fusion detected by next-generation sequencing (NGS). We discuss the findings in comparison to BEND2-fusion associated neoplasms reported in the head and neck region in the literature to date.

A Cohort Study Exploring HPV Vaccination Beliefs Among Oral Health Providers: Broadening the Scope of Education and Administration.

Background/objectives: There is potential utility and increasing interest in engaging professionals in non-traditional vaccination settings to participate in efforts to reduce human papillomavirus (HPV)-related cancer. This study assessed the impact of a multi-disciplinary HPV educational intervention on oral health care professionals' perceived role, comfort level, and scope of practice in HPV-related cancer prevention efforts.

Methods: The virtual educational intervention was provided by a multi-disciplinary panel of experts.

Occurrence, Bioaccumulation, and Human Exposure Risk of the Antiandrogenic Fluorescent Dye 7-(Dimethylamino)-4-methylcoumarin and 7-(Diethylamino)-4-methylcoumarin in the Dongjiang River Basin, South China.

Recently, 7-diethylamino-4-methylcoumarin (DEAMC) has been identified as a potent antiandrogenic compound in the surface water; however, little is known about the antiandrogenic potentials of other synthetic coumarins and their occurrence in the aquatic ecosystem. In this study, for the first time, we observed that 7-dimethylamino-4-methylcoumarin (DAMC) elicited androgen receptor (AR) antagonistic activity with a 50% inhibitory concentration (IC) of 1.46 µM, which is 14.

Sensitivity of Acoustic Voice Quality Measures in Simulated Reverberation Conditions.

Room reverberation can affect oral/aural communication and is especially critical in computer analysis of voice. High levels of reverberation can distort voice recordings, impacting the accuracy of quantifying voice production quality and vocal health evaluations. This study quantifies the impact of additive simulated reverberation on otherwise clean voice recordings as reflected in voice metrics commonly used for voice quality evaluation.

Efficacy of Novel Digital-Based Surgical Guide in the Limited Interocclusal Distance.

Accurate implant placement is essential for achieving successful outcomes. To aid in this, digitally designed surgical guides have been introduced. Both closed-sleeve and open-sleeve designs are commonly utilized.

Sequential Endoluminal Doxorubicin and Gemcitabine Alternating Weekly with Sequential Mitomycin and Docetaxel for Recurrent Non-Muscle Invasive Urothelial Carcinoma.

After first-line treatment failure, patients with non-muscle invasive urothelial carcinoma (NMIUC) are recommended to undergo radical cystectomy. However, those unable to pursue radical surgery or desiring bladder preservation require effective salvage therapies. Multi-agent treatment regimens are particularly useful for targeting the complex resistance mechanisms of recurrent UC.

The utility of renal sonographic measurements in differentiating children with grades 2, 3, and 4 hydronephrosis.

Introduction: Prior analysis of children with grade 3 and 4 congenital hydronephrosis demonstrated that renal medullary pyramidal thickness (PT) is predictive of subsequent pyeloplasty (area under the curve [AUC] = 0.78). The objective of this study was to further analyze the utility of sonographic measurements including PT, anteroposterior pelvic diameter (APD), and renal length with an expansion of the number of infants with hydronephrotic kidneys including grades 2, 3, and 4 hydronephrosis.