Improved Tensor Current Limit from

A precision measurement of the ß^{+} decay of ^{8}B was performed using the Beta-decay Paul Trap to determine the ß-ν angular correlation coefficient a_{ßν}. The experimental results were combined with new ab initio symmetry-adapted no-core shell-model calculations to yield the second-most precise measurement from Gamow-Teller decays, a_{ßν}=-0.3345±0.0019_{stat}±0.0021_{syst}. This value agrees with the standard model value of -1/3 and improves uncertainties in ^{8}B by nearly a factor of 2. By combining results from ^{8}B and ^{8}Li, a tight limit on tensor current coupling to right-handed neutrinos was obtained. A recent global evaluation of all other precision ß decay studies suggested a nonzero value for right-handed neutrino coupling in contradiction with the standard model at just above 3σ. The present results are of comparable sensitivity and do not support this finding.

Biochemical and metabolic characterization of a G6PC2 inhibitor.

Three glucose-6-phosphatase catalytic subunits, that hydrolyze glucose-6-phosphate (G6P) to glucose and inorganic phosphate, have been identified, designated G6PC1-3, but only G6PC1 and G6PC2 have been implicated in the regulation of fasting blood glucose (FBG). Elevated FBG has been associated with multiple adverse clinical outcomes, including increased risk for type 2 diabetes and various cancers. Therefore, G6PC1 and G6PC2 inhibitors that lower FBG may be of prophylactic value for the prevention of multiple conditions. The studies described here characterize a G6PC2 inhibitor, designated VU0945627, previously identified as Compound 3. We show that VU0945627 preferentially inhibits human G6PC2 versus human G6PC1 but activates human G6PC3. VU0945627 is a mixed G6PC2 inhibitor, increasing the Km but reducing the Vmax for G6P hydrolysis. PyRx virtual docking to an AlphaFold2-derived G6PC2 structural model suggests VU0945627 binds two sites in human G6PC2. Mutation of residues in these sites reduces the inhibitory effect of VU0945627. VU0945627 does not inhibit mouse G6PC2 despite its 84% sequence identity with human G6PC2. Mutagenesis studies suggest this lack of inhibition of mouse G6PC2 is due, in part, to a change in residue 318 from histidine in human G6PC2 to proline in mouse G6PC2. Surprisingly, VU0945627 still inhibited glucose cycling in the mouse islet-derived ßTC-3 cell line. Studies using intact mouse liver microsomes and PyRx docking suggest that this observation can be explained by an ability of VU0945627 to also inhibit the G6P transporter SLC37A4. These data will inform future computational modeling studies designed to identify G6PC isoform-specific inhibitors.

Screening H3 Histone Acetylation in a Wild Bird, the House Sparrow (Passer Domesticus).

Epigenetic mechanisms are increasingly understood to have major impacts across ecology. However, one molecular epigenetic mechanism, DNA methylation, currently dominates the literature. A second mechanism, histone modification, is likely important to ecologically relevant phenotypes and thus warrants investigation, especially because molecular interplay between methylation and histone acetylation can strongly affect gene expression. There are a limited number of histone acetylation studies on non-model organisms, yet those that exist show that it can impact gene expression and phenotypic plasticity. Wild birds provide an excellent system to investigate histone acetylation, as free-living individuals must rapidly adjust to environmental change. Here, we screen histone acetylation in the house sparrow (Passer domesticus); we studied this species because DNA methylation was important in the spread of this bird globally. This species has one of the broadest geographic distributions in the world, and part of this success is related to the way that it uses methylation to regulate its gene expression. Here, we verify that a commercially available assay that was developed for mammals can be used in house sparrows. We detected high variance in histone acetylation among individuals in both liver and spleen tissue. Further, house sparrows with higher epigenetic potential in the Toll Like Receptor-4 (TLR-4) promoter (i.e., CpG content) had higher histone acetylation in liver. Also, there was a negative correlation between histone acetylation in spleen and TLR-4 expression. In addition to validating a method for measuring histone acetylation in wild songbirds, this study also shows that histone acetylation is related to epigenetic potential and gene expression, adding a new study option for ecological epigenetics.

Achieving white blood cell equity: are the safety profiles of biosimilar and reference pegfilgrastims comparable?

Biosimilars can provide choices for patients and may provide cost savings; however, their uptake has been slow in the USA, in part due to limited knowledge. To provide additional confidence in US pegfilgrastim biosimilars, this narrative review compared the safety profiles of biosimilar pegfilgrastims, currently approved or filed for approval in the USA, with the EU- and US-approved reference pegfilgrastims. Headache and bone pain were common to biosimilars and reference products and occurred at a similar incidence. Clinical trial data on the safety profiles of biosimilar pegfilgrastims and reference products have demonstrated similarity and comparability, with no unexpected safety outcomes. Overall, the safety profiles of biosimilar pegfilgrastims and reference pegfilgrastims demonstrated a high degree of similarity and comparability.

Pegfilgrastim is a biologic drug (one made in living cells such as bacteria) that is given to some patients being treated for cancer. Pegfilgrastim is prescribed to reduce a patient's risk of infection due to a weakened immune system caused by various chemotherapy treatment plans. A biosimilar is a type of biologic medicine that is highly similar to a US FDA-approved reference biologic, and is often cheaper, making it more widely available to patients. As of March 2023, there are eight pegfilgrastim biosimilars (six approved and two awaiting approval by the FDA). This review compared the side effects for the reference pegfilgrastim with the biosimilar pegfilgrastims. The side effects in general and the side effects from treatment were similar for the reference pegfilgrastim and for the biosimilar pegfilgrastims, with the most common side effects being headache and bone pain. Serious side effects such as allergic reactions or problems with the spleen were very low and were also similar between the reference pegfilgrastim and the biosimilar pegfilgrastims. These results show that the safety of the biosimilar pegfilgrastims was similar to the reference pegfilgrastim, with no unexpected side effects. With comparable safety to their reference product, biosimilars have the potential to improve patient access to more affordable treatment options.

Soft Tissue Mass Extramedullary Plasmacytoma Following Radiation Therapy for Solitary Bone Plasmacytoma.

Soft tissue involvement in extramedullary plasmacytoma (EMP) is an exceptionally rare occurrence within the spectrum of plasma cell neoplasms. This case report presents the unique scenario of a patient who developed a soft tissue mass EMP subsequent to receiving radiation therapy for a solitary bone plasmacytoma at a distinct anatomical site. The primary objective of this report is to elucidate the clinical characteristics, diagnostic complexities, and management considerations associated with this uncommon presentation. Through a comprehensive review of existing literature, we aim to provide valuable insights and expertise to healthcare providers involved in the assessment and treatment of similar cases.

"Teaching somebody else makes you a better person:" A phenomenological exploration of the importance of informal peer support for individuals with spinal cord injury.

BACKGROUND: Peer support is widely recognized as an important aspect of health promotion for individuals with spinal cord injury (SCI). Reports indicate positive effects for the recipients of either informal and formal peer support. The experience can also be meaningful to the person(s) providing support, although the value to providers is not well studied. OBJECTIVE: This study examines the experience of provision of and receipt of informal peer support for individuals with SCI through semi-structured interviews. METHODS: Data were analysed using a qualitative phenomenological approach. 16 participants with SCI participated in the study. RESULTS: Three main themes were developed, each describing different benefits of peer support from the perspective of both members of the peer support dyad. First, participants found personal satisfaction from using their own experiences to help others adjust to their disability. Participants also noted that they learned how to complete activities of daily living as well as how to be autonomous in travel from others with SCI. Finally, participants spoke of the intrinsic benefit in teaching others with SCI. CONCLUSIONS: This study provides a novel understanding of the importance of informal peer support for individuals with SCI. Practitioners should provide opportunities for individuals with SCI to develop informal peer relationships with others who have sustained SCI.

Exceedingly Rare Bilateral Synchronous Germ Cell Testicular Tumors With Different Histopathological Features.

Bilateral synchronous testicular tumors are a relatively uncommon occurrence, especially when they involve germ cell tumors of different histology. In this context, we present a compelling case report of a male patient who was diagnosed with bilateral synchronous germ cell testicular tumors, with one being a seminoma and the other a non-seminomatous germ cell tumor (NSGCT). The coexistence of two distinct histological types, seminoma and NSGCT, necessitates a comprehensive diagnostic approach to accurately identify and characterize each tumor. This underscores the importance of clinical history, physical examination, imaging techniques, and histopathological analysis to establish an appropriate diagnosis. Careful consideration must be given to factors such as tumor stage, histological subtype, and individual patient characteristics to determine the most suitable treatment strategy. Treatment options may encompass a combination of surgery, chemotherapy, and radiation therapy, tailored to each tumor's specific characteristics and the patient's overall health. By highlighting this unique case, we aim to underscore the significance of meticulous evaluation and accurate diagnosis when confronted with bilateral synchronous testicular tumors of different histology.

Direct Mass Measurements to Inform the Behavior of

Nuclear isomer effects are pivotal in understanding nuclear astrophysics, particularly in the rapid neutron-capture process where the population of metastable isomers can alter the radioactive decay paths of nuclei produced during astrophysical events. The ß-decaying isomer ^{128m}Sb was identified as potentially impactful since the ß-decay pathway along the A=128 isobar funnels into this state bypassing the ground state. We report the first direct mass measurements of the ^{128}Sb isomer and ground state using the Canadian Penning Trap mass spectrometer at Argonne National Laboratory. We find mass excesses of -84564.8(25) keV and -84608.8(21) keV, respectively, resulting in an excitation energy for the isomer of 43.9(33) keV. These results provide the first key nuclear data input for understanding the role of ^{128m}Sb in nucleosynthesis, and we show that it will influence the flow of the rapid neutron-capture process.

Improved Limit on Tensor Currents in the Weak Interaction from

The electroweak interaction in the standard model is described by a pure vector-axial-vector structure, though any Lorentz-invariant component could contribute. In this Letter, we present the most precise measurement of tensor currents in the low-energy regime by examining the ß-ν[over ¯] correlation of trapped ^{8}Li ions with the Beta-decay Paul Trap. We find a_{ßν}=-0.3325±0.0013_{stat}±0.0019_{syst} at 1σ for the case of coupling to right-handed neutrinos (C_{T}=-C_{T}^{'}), which is consistent with the standard model prediction.

"It Helps Me With Everything": A Qualitative Study of the Importance of Exercise for Individuals With Spinal Cord Injury.

Background: The influence of exercise after spinal cord injury (SCI) is a topic important to both clinicians and researchers. The impact of exercise for individuals with SCI is often studied quantitively, with a large focus on the physiological adaptations to exercise intervention. Objectives: This study explores individualized experiences of exercise for people with SCI. Methods: A phenomenological approach was utilized to qualitatively study the experiences of exercise for 16 individuals with SCI. Results: Participants described multiple benefits of exercise, including increased independence, improved mental health, and increased engagement in social activity. Conclusion: This study provides novel information about attitudes toward exercise held by individuals with SCI and a more thorough understanding of concepts that are well researched.

Retrospective Case-Control Study of Communication and Motor Abilities in 143 Children With Suspected Childhood Apraxia of Speech: Effect of Concomitant Diagnosis.

Purpose: This study sought to determine if children with childhood apraxia of speech (CAS) plus another major diagnosis (CAS+) are equivalent in communication and motor profiles to those with a primary diagnosis of CAS and no indication or report of any other diagnosis (CAS-Primary). Method: This retrospective case-control study included a chart review of 143 children who were suspected of having CAS at Children's Hospital-Wisconsin between 1998 and 2004. Participants were between 30 and 127 months old and included 107 males. Participants were assigned to the suspected CAS-Primary group (n = 114) if they had characteristics of CAS but no other major diagnosis (e.g., galactosemia) and to the CAS+ group (n = 29) if a comorbid diagnosis was present. Groups were compared across demographic, communication, and motor characteristics. Results: Children with CAS+ evidenced more severe motor profiles than those with CAS-Primary, χ2 = (1, n = 122) = 4.952, p = .026, and a small-to-medium effect size (Φ = .201). On average, communication profiles also tended to be more severe among those with CAS+ wherein receptive language was poorer and phonemic inventories were smaller than those with CAS-Primary. Conclusions: These retrospective data suggest that comorbid diagnosis may play an important role in communication and motor development in children with suspected CAS. These exploratory findings should motivate future prospective studies that consider the role of concomitant diagnoses in symptom profile and response to treatment in children with CAS.

Clinical Outcomes for Plasma-Based Comprehensive Genomic Profiling Versus Standard-of-Care Tissue Testing in Advanced Non-Small Cell Lung Cancer.

BACKGROUND: Somatic genomic testing is recommended by numerous expert guidelines to inform targeted therapy treatment for patients with advanced nonsquamous non-small cell lung cancer (aNSCLC). The NILE study was a prospective observational study that demonstrated noninferiority of cell-free circulating tumor DNA (cfDNA)-based tumor genotyping compared to tissue-based genotyping to find targetable genomic alterations in patients with newly diagnosed nonsquamous aNSCLC. As the cohort has matured, clinical outcomes data can now be analyzed. METHODS: This prospective, multicenter North American study enrolled patients with previously untreated nonsquamous aNSCLC who had standard of care (SOC) tissue genotyping performed and concurrent comprehensive cfDNA analysis (Guardant360). Patients with targetable genomic alterations, as defined by NCCN guidelines, who were treated with physician's choice of therapy had objective response rates, disease control rate, and time to treatment collected and compared to published outcomes. RESULTS: Among 282 patients, 89 (31.6%) had an actionable biomarker, as defined by NCCN, detected by tissue (21.3%) and/or cfDNA (27.3%) analysis. Sixty-one (68.5%) of these were treated with an FDA-approved targeted therapy guided by somatic genotyping results (EGFR, ALK, ROS1). Thirty-three patients were eligible for clinical response evaluation and demonstrated an objective response rate of 58% and disease control rate of 94%. Twenty-five (76%) and 17 (52%) achieved a durable response > 6 months and 12 months, respectively. The time to treatment (TtT) was significantly faster for cfDNA-informed biomarker detection as compared to tissue genotyping (18 vs. 31 days, respectively; P = .0008). CONCLUSIONS: cfDNA detects guideline-recommended biomarkers at a rate similar to tissue genotyping, and therapeutic outcomes based on plasma-based comprehensive genomic profiling are comparable to published targeted therapy outcomes with tissue profiling, even in community-based centers.

The maturational gradient of infant vocalizations: Developmental stages and functional modules.

Stage models have been influential in characterizing infant vocalizations in the first year of life. These models are basically descriptive and do not explain why certain types of vocal behaviors occur within a particular stage or why successive patterns of vocalization occur. This review paper summarizes and elaborates a theory of Developmental Functional Modules (DFMs) and discusses how maturational gradients in the DFMs explain age typical vocalizations as well as the transitions between successive stages or other static forms. Maturational gradients are based on biological processes that effect the reconfiguration and remodeling of the respiratory, laryngeal, and craniofacial systems during infancy. From a dynamic systems perspective, DFMs are part of a complex system with multiple degrees of freedom that can achieve stable performance with relatively few control variables by relying on principles such as synergies, self-organization, nonlinear performance, and movement variability.

Oral and Laryngeal Diadochokinesis Across the Life Span: A Scoping Review of Methods, Reference Data, and Clinical Applications.

PURPOSE: The aim of this study was to conduct a scoping review of research on oral and laryngeal diadochokinesis (DDK) in children and adults, either typically developing/developed or with a clinical diagnosis. METHOD: Searches were conducted with PubMed/MEDLINE, Google Scholar, CINAHL, and legacy sources in retrieved articles. Search terms included the following: DDK, alternating motion rate, maximum repetition rate, sequential motion rate, and syllable repetition rate. RESULTS: Three hundred sixty articles were retrieved and included in the review. Data source tables for children and adults list the number and ages of study participants, DDK task, and language(s) spoken. Cross-sectional data for typically developing children and typically developed adults are compiled for the monosyllables /pʌ/, /tʌ/, and /kʌ/; the trisyllable /pʌtʌkʌ/; and laryngeal DDK. In addition, DDK results are summarized for 26 disorders or conditions. DISCUSSION: A growing number of multidisciplinary reports on DDK affirm its role in clinical practice and research across the world. Atypical DDK is not a well-defined singular entity but rather a label for a collection of disturbances associated with diverse etiologies, including motoric, structural, sensory, and cognitive. The clinical value of DDK can be optimized by consideration of task parameters, analysis method, and population of interest.

Telehealth in Oncology: ASCO Standards and Practice Recommendations.

PURPOSE: To provide standards and practice recommendations specific to telehealth in oncology. METHODS: A systematic review of the literature on telehealth in oncology was performed, including the use of technologies and telecommunications systems, and other electronic methods of care delivery and sharing of information with patients. The evidence base was combined with the opinion of the ASCO Telehealth Expert Panel to develop telehealth standards and guidance. Public comments were solicited and considered in preparation of the final manuscript. RESULTS: The Expert Panel determined that general guidance on implementing telehealth across general and specialty settings has been published previously and these resources are endorsed. A systematic search for studies on topics specific to oncology resulted in the inclusion of two clinical practice guidelines, 12 systematic reviews, and six primary studies. STANDARDS AND GUIDANCE: Standards and guidance are provided for which patients in oncology can be seen via telehealth, establishment of the doctor-physician relationship, role of allied health professionals, role of advanced practice providers, multidisciplinary cancer conferences, and teletrials in oncology. Additional information is available at www.asco.org/standards.

Occupational and Personal Consequences of the COVID-19 Pandemic on US Oncologist Burnout and Well-Being: A Study From the ASCO Clinician Well-Being Task Force.

INTRODUCTION: The COVID-19 pandemic is an unprecedented global crisis profoundly affecting oncology care delivery. PURPOSE: This study will describe the occupational and personal consequences of the COVID-19 pandemic on oncologist well-being and patient care. MATERIALS AND METHODS: Four virtual focus groups were conducted with US ASCO member oncologists (September-November 2020). Inquiry and subsequent discussions centered on self-reported accounts of professional and personal COVID-19 experiences affecting well-being, and oncologist recommendations for well-being interventions that the cancer organization and professional societies (ASCO) might implement were explored. Qualitative interviews were analyzed using Framework Analysis. RESULTS: Twenty-five oncologists were interviewed: median age 44 years (range: 35-69 years), 52% female, 52% racial or ethnic minority, 76% medical oncologists, 64% married, and an average of 51.5 patients seen per week (range: 20-120). Five thematic consequences emerged: (1) impact of pre-COVID-19 burnout, (2) occupational or professional limitations and adaptations, (3) personal implications, (4) concern for the future of cancer care and the workforce, and (5) recommendations for physician well-being interventions. Underlying oncologist burnout exacerbated stressors associated with disruptions in care, education, research, financial practice health, and telemedicine. Many feared delays in cancer screening, diagnosis, and treatment. Oncologists noted personal and familial stressors related to COVID-19 exposure fears and loss of social support. Many participants strongly considered working part-time or taking early retirement. Yet, opportunities arose to facilitate personal growth and rise above pandemic adversity, fostering greater resilience. Recommendations for organizational well-being interventions included psychologic or peer support resources, flexible time-off, and ASCO and state oncology societies involvement to develop care guidelines, well-being resources, and mental health advocacy. CONCLUSION: Our study suggests that the COVID-19 pandemic has adversely affected oncologist burnout, fulfillment, practice health, cancer care, and workforce. It illuminates where professional organizations could play a significant role in oncologist well-being.

Creating a Blueprint of Well-Being in Oncology: An Approach for Addressing Burnout From ASCO's Clinician Well-Being Taskforce.

Optimizing the well-being of the oncology clinician has never been more important. Well-being is a critical priority for the cancer organization because burnout adversely impacts the quality of care, patient satisfaction, the workforce, and overall practice success. To date, 45% of U.S. ASCO member medical oncologists report experiencing burnout symptoms of emotional exhaustion and depersonalization. As the COVID-19 pandemic remains widespread with periods of outbreaks, recovery, and response with substantial personal and professional consequences for the clinician, it is imperative that the oncologist, team, and organization gain direct access to resources addressing burnout. In response, the Clinician Well-Being Task Force was created to improve the quality, safety, and value of cancer care by enhancing oncology clinician well-being and practice sustainability. Well-being is an integrative concept that characterizes quality of life and encompasses an individual's work- and personal health-related environmental, organizational, and psychosocial factors. These resources can be useful for the cancer organization to develop a well-being blueprint: a detailed start plan with recognized strategies and interventions targeting all oncology stakeholders to support a culture of community in oncology.

Developmental Functional Modules in Infant Vocalizations.

Purpose Developmental functional modules (DFMs) are biological modules that are defined by their structural (morphological), functional, or developmental elements, and, in some cases, all three of these. This review article considers the hypothesis that vocal development in the first year of life can be understood in large part with respect to DFMs that characterize the speech production system. Method Literature is reviewed on relevant embryology, orofacial reflexes, craniofacial muscle properties, stages of vocal development, and related topics to identity candidates for DFMs. Results The following DFMs are identified and described: laryngeal, pharyngo-laryngeal, mandibular, velopharyngeal, labial complex, and lingual complex. These DFMs and their submodules, considered along with phenomena such as rhythmic movements, account for several well-documented features of vocal development in the first year of life. The proposed DFMs, rooted in embryologic, histologic, and kinematic properties, serve as low-dimensional control variables for the developing vocal tract. Each DFM is semi-autonomous but interacts with other DFMs to produce patterns of vocal behavior. Discussion Considered in relation to contemporary profiles and models of vocal development in the first year of life, DFMs have interpretive and explanatory value. DFMs complement other approaches in the study of infant vocalizations and are grounded in biology.

Electromyography-Driven Exergaming in Wheelchairs on a Mobile Platform: Bench and Pilot Testing of the WOW-Mobile Fitness System.

BACKGROUND: Implementing exercises in the form of video games, otherwise known as exergaming, has gained recent attention as a way to combat health issues resulting from sedentary lifestyles. However, these exergaming apps have not been developed for exercises that can be performed in wheelchairs, and they tend to rely on whole-body movements. OBJECTIVE: This study aims to develop a mobile phone app that implements electromyography (EMG)-driven exergaming, to test the feasibility of using this app to enable people in wheelchairs to perform exergames independently and flexibly in their own home, and to assess the perceived usefulness and usability of this mobile health system. METHODS: We developed an Android mobile phone app (Workout on Wheels, WOW-Mobile) that senses upper limb muscle activity (EMG) from wireless body-worn sensors to drive 3 different video games that implement upper limb exercises designed for people in wheelchairs. Cloud server recordings of EMG enabled long-term monitoring and feedback as well as multiplayer gaming. Bench testing of data transmission and power consumption were tested. Pilot testing was conducted on 4 individuals with spinal cord injury. Each had a WOW-Mobile system at home for 8 weeks. We measured the minutes for which the app was used and the exergames were played, and we integrated EMG as a measure of energy expended. We also conducted a perceived usefulness and usability questionnaire. RESULTS: Bench test results revealed that the app meets performance specifications to enable real-time gaming, cloud storage of data, and live cloud server transmission for multiplayer gaming. The EMG sampling rate of 64 samples per second, in combination with zero-loss data communication with the cloud server within a 10-m range, provided seamless control over the app exergames and allowed for offline data analysis. Each participant successfully used the WOW-Mobile system at home for 8 weeks, using the app for an average of 146 (range 89-267) minutes per week with the system, actively exergaming for an average of 53% of that time (39%-59%). Energy expenditure, as measured by integrated EMG, was found to be directly proportional to the time spent on the app (Pearson correlation coefficient, r=0.57-0.86, depending on the game). Of the 4 participants, 2 did not exercise regularly before the study; these 2 participants increased from reportedly exercising close to 0 minutes per week to exergaming 58 and 158 minutes on average using the WOW-Mobile fitness system. The perceived usefulness of WOW-Mobile in motivating participants to exercise averaged 4.5 on a 5-point Likert scale and averaged 5 for the 3 participants with thoracic level injuries. The mean overall ease of use score was 4.25 out of 5. CONCLUSIONS: Mobile app exergames driven by EMG have promising potential for encouraging and facilitating fitness for individuals in wheelchairs who have maintained arm and hand mobility.