Open-Label Randomized Clinical Trial to Assess the Effects of Preoperative Acupuncture in High Anxiety Patients Undergoing Total Knee or Hip Arthroplasty.

Preoperative state anxiety is a known predisposing factor for enhanced postoperative pain and hindered recovery following total knee or hip replacement. Acupuncture administered preoperatively has been associated with reduced anxiety in surgical studies, yet evidence of its efficacy in the orthopedic surgical setting is limited. This study investigated the effects of preoperative acupuncture on preoperative anxiety and pain and compared acute postoperative pain between acupuncture and control patient groups.

AspSnFR: A genetically encoded biosensor for real-time monitoring of aspartate in live cells.

Aspartate is crucial for nucleotide synthesis, ammonia detoxification, and maintaining redox balance via the malate-aspartate-shuttle (MAS). To disentangle these multiple roles of aspartate metabolism, tools are required that measure aspartate concentrations in real time and in live cells. We introduce AspSnFR, a genetically encoded green fluorescent biosensor for intracellular aspartate, engineered through displaying and screening biosensor libraries on mammalian cells.

Individuals' experiences in genetic counseling and predictive testing for familial amyotrophic lateral sclerosis.

As clinical genetic testing in the amyotrophic lateral sclerosis (ALS) diagnostic setting increases, the identification of at-risk family members has also expanded. No practice guidelines specifically for predictive genetic testing exist, and few studies about the psychological impacts of testing in this subgroup have occurred, limiting the ability to tailor recommendations and counseling in this community. We surveyed asymptomatic individuals at risk for inheriting an ALS-associated gene mutation.

Exploring the evolving roles of clinical geneticists and genetic counselors in the era of genomic medicine.

The increased utilization of clinical genomic sequencing in the past decade has ushered in the era of genomic medicine, requiring genetics providers to acquire new skills and adapt their practices. The change in workplace responsibilities of clinical/medical geneticists (CMGs) and genetic counselors (GCs) in North America, due to the evolution of genetic testing, has not been studied. We surveyed CMGs (n = 80) and GCs (n = 127) with experience in general/pediatric genetics to describe their current practice of clinical tasks and the change in regularity of performing these tasks over the past 5-10 years.

Genetic counselors' utilization of ChatGPT in professional practice: A cross-sectional study.

Purpose: The precision medicine era has seen increased utilization of artificial intelligence (AI) in the field of genetics. We sought to explore the ways that genetic counselors (GCs) currently use the publicly accessible AI tool Chat Generative Pre-trained Transformer (ChatGPT) in their work.

Methods: GCs in North America were surveyed about how ChatGPT is used in different aspects of their work.

A general method for the development of multicolor biosensors with large dynamic ranges.

Fluorescent biosensors enable the study of cell physiology with spatiotemporal resolution; yet, most biosensors suffer from relatively low dynamic ranges. Here, we introduce a family of designed Förster resonance energy transfer (FRET) pairs with near-quantitative FRET efficiencies based on the reversible interaction of fluorescent proteins with a fluorescently labeled HaloTag. These FRET pairs enabled the straightforward design of biosensors for calcium, ATP and NAD with unprecedented dynamic ranges.

The utility of limited Spanish proficiency in interpreted genetic counseling sessions.

Professional interpreters are an integral component of healthcare for Spanish-speaking individuals with limited English proficiency (LEP). Research has demonstrated that errors in interpretation are common and can contribute to poor outcomes for Spanish-speaking clients. Providers with some Spanish proficiency may be able to detect clinically significant interpretation errors, potentially limiting negative clinical outcomes and helping to reduce health disparities for clients with LEP.

Clinical utility of exome sequencing in a pediatric epilepsy cohort.

Objective: Exome sequencing (ES) has played an important role in the identification of causative variants for individuals with epilepsy and has proven to be a valuable diagnostic tool. Less is known about its clinical utility once a diagnosis is received. This study systematically reviewed the impact of ES results on clinical decision-making and patient care in a pediatric epilepsy cohort at a tertiary care medical center.

Discovery of potent and selective HER2 inhibitors with efficacy against HER2 exon 20 insertion-driven tumors, which preserve wild-type EGFR signaling.

Oncogenic alterations in human epidermal growth factor receptor 2 (HER2) occur in approximately 2% of patients with non-small cell lung cancer and predominantly affect the tyrosine kinase domain and cluster in exon 20 of the ERBB2 gene. Most clinical-grade tyrosine kinase inhibitors are limited by either insufficient selectivity against wild-type (WT) epidermal growth factor receptor (EGFR), which is a major cause of dose-limiting toxicity or by potency against HER2 exon 20 mutant variants. Here we report the discovery of covalent tyrosine kinase inhibitors that potently inhibit HER2 exon 20 mutants while sparing WT EGFR, which reduce tumor cell survival and proliferation in vitro and result in regressions in preclinical xenograft models of HER2 exon 20 mutant non-small cell lung cancer, concomitant with inhibition of downstream HER2 signaling.

Sustainable and highly controlled aryl couplings revealed by systematic assessment of photoactivatable linkers.

The controlled synthesis of biphenyls, which play a prominent role in pharmaceuticals, agrochemicals, and liquid crystals, typically requires hazardous organometallic reagents, aryl halides, and heavy metal catalysts. We recently reported a metal-free, photochemical alternative ("photosplicing") for the selective preparation of a wide range of pharmaceutically important biphenyls. Whereas the traceless sulfonamide linker enables and controls the aryl coupling, unwanted toxic byproducts are released.

Adjuvant radiotherapy and stereotactic radiosurgery in grade 3 meningiomas - a systematic review and meta-analysis.

Malignant meningioma is a rare, aggressive form of meningioma. Radiation is commonly included in treatment guidelines either as adjuvant radiotherapy (RT) or stereotactic radiosurgery (SRS). Nevertheless, the treatment recommendations are not supported by prospective comparative trials and systematical, critical evaluation of supportive evidence is lacking.

A report of the AGCPD task force to evaluate associations between select admissions requirements, demographics, and performance on ABGC certification examination.

Graduation from a genetic counseling graduate program accredited by the Accreditation Council of Genetic Counseling and certification obtained by passing the American Board of Genetic Counseling (ABGC) certification examination are increasingly required to practice as a genetic counselor in the USA. Despite the ABGC certification examination serving as a gateway to the genetic counseling career, there have been no research studies to date that have examined what variables are associated with examination performance. Therefore, the Association of Genetic Counseling Program Directors established a Task Force to assess whether trainee demographics, Grade point average (GPA) and Graduate Record Exam (GRE®) percentile scores are associated with passing the ABGC certification examination on the first attempt.

The evolution of genetic counseling graduate education in New York City during the COVID-19 pandemic: In the eye of the storm.

The COVID-19 pandemic has ravaged the globe in the past year, demanding shifts in all aspects of life including health profession education. The New York City area was the first major United States epicenter and is home to four genetic counseling graduate programs. We set out to explore the multifaceted programmatic changes required from the four institutions in an early pandemic epicenter, providing the longest time horizon available for assessing the implications of this restructuring on graduate education in the profession.

Getting a Grip on the Undrugged: Targeting β-Catenin with Fragment-Based Methods.

Aberrant WNT pathway activation, leading to nuclear accumulation of β-catenin, is a key oncogenic driver event. Mutations in the tumor suppressor gene APC lead to impaired proteasomal degradation of β-catenin and subsequent nuclear translocation. Restoring cellular degradation of β-catenin represents a potential therapeutic strategy.

Drugging all RAS isoforms with one pocket.

Activating mutations in the three human RAS genes, , and , are among the most common oncogenic drivers in human cancers. Covalent KRAS inhibitors, which bind to the switch II pocket in the 'off state' of KRAS, represent the first direct KRAS drugs that entered human clinical trials. However, the remaining 85% of non-KRAS-driven cancers remain undrugged as do NRAS and HRAS and no drugs targeting the 'on state' have been discovered so far.

The cognitive augmented mobility program (CAMP): feasibility and preliminary efficacy.

Background: Best evidence suggests incorporating task-specific training, aerobics, and strengthening to improve mobility and gait in persons with stroke (PWS). Related research suggests incorporating cognitive problem-solving strategy training may lead to better skill maintenance and transfer. The present study examined the feasibility and preliminary outcomes of an evidence-based cognitive augmented mobility program (CAMP) for PWS.

Genetic Counseling for Neurofibromatosis 1, Neurofibromatosis 2, and Schwannomatosis-Practice Resource of the National Society of Genetic Counselors.

The goal of this practice resource is to provide genetic counselors and other healthcare professionals with a resource to reference when providing genetic counseling services to individuals and families undergoing evaluation for neurofibromatosis (NF) or who have received a diagnosis of NF, including NF1, NF2, and schwannomatosis. This resource represents the opinions of a multi-center working group of Certified Genetic Counselors with experience in the care of individuals with NF, providing topics to be considered for the incorporation into a clinical genetic counseling session.

Reflections on diversity, equity, and inclusion in genetic counseling education.

Through self-reflection, self-education, and with a learning mindset each of us has embarked on a personal path to understand the impact of racism in our personal and professional lives. This personal work is ongoing, though it was through our individual paths that led us to engage in dialogue on race and racism at the 38th National Society of Genetic Counselors Annual Conference. We initially did not know each other; however, we were drawn by a mutual desire to further the conversation and sought connection with each other after the Conversations Around Diversity Platform Presentations.

A Grid Map Based Approach to Identify Nonobvious Ligand Design Opportunities in 3D Protein Structure Ensembles.

Three-dimensional protein structures are a key requisite for structure-based drug discovery. For many highly relevant targets, medicinal chemists are confronted with large numbers of target structures in their apo-forms or in complex with a wealth of different ligands. To exploit the full potential of such structure ensembles, in terms of aggregated knowledge that informs design, it is desirable to extract a manageable number of structures that provide a maximum of ligand design opportunities.

Localization of Drosophila CENP-A to non-centromeric sites depends on the NuRD complex.

Centromere function requires the presence of the histone H3 variant CENP-A in most eukaryotes. The precise localization and protein amount of CENP-A are crucial for correct chromosome segregation, and misregulation can lead to aneuploidy. To characterize the loading of CENP-A to non-centromeric chromatin, we utilized different truncation- and localization-deficient CENP-A mutant constructs in Drosophila melanogaster cultured cells, and show that the N-terminus of Drosophila melanogaster CENP-A is required for nuclear localization and protein stability, and that CENP-A associated proteins, rather than CENP-A itself, determine its localization.

Start Selective and Rigidify: The Discovery Path toward a Next Generation of EGFR Tyrosine Kinase Inhibitors.

The epidermal growth factor receptor (EGFR), when carrying an activating mutation like del19 or L858R, acts as an oncogenic driver in a subset of lung tumors. While tumor responses to tyrosine kinase inhibitors (TKIs) are accompanied by marked tumor shrinkage, the response is usually not durable. Most patients relapse within two years of therapy often due to acquisition of an additional mutation in EGFR kinase domain that confers resistance to TKIs.