Coupled pulsatile vascular and paravascular fluid dynamics in the human brain.

BACKGROUND: Cardiac pulsation propels blood through the cerebrovascular network to maintain cerebral homeostasis. The cerebrovascular network is uniquely surrounded by paravascular cerebrospinal fluid (pCSF), which plays a crucial role in waste removal, and its flow is suspected to be driven by arterial pulsations. Despite its importance, the relationship between vascular and paravascular fluid dynamics throughout the cardiac cycle remains poorly understood in humans. METHODS: In this study, we developed a non-invasive neuroimaging approach to investigate the coupling between pulsatile vascular and pCSF dynamics within the subarachnoid space of the human brain. Resting-state functional MRI (fMRI) and dynamic diffusion-weighted imaging (dynDWI) were retrospectively cardiac-aligned to represent cerebral hemodynamics and pCSF motion, respectively. We measured the time between peaks (∆TTP) in d d ϕ f M R I and dynDWI waveforms and measured their coupling by calculating the waveforms correlation after peak alignment (correlation at aligned peaks). We compared the ∆TTP and correlation at aligned peaks between younger [mean age: 27.9 (3.3) years, n = 9] and older adults [mean age: 70.5 (6.6) years, n = 20], and assessed their reproducibility within subjects and across different imaging protocols. RESULTS: Hemodynamic changes consistently precede pCSF motion. ∆TTP was significantly shorter in younger adults compared to older adults (-0.015 vs. -0.069, p < 0.05). The correlation at aligned peaks were high and did not differ between younger and older adults (0.833 vs. 0.776, p = 0.153). The ∆TTP and correlation at aligned peaks were robust across fMRI protocols (∆TTP: -0.15 vs. -0.053, p = 0.239; correlation at aligned peaks: 0.813 vs. 0.812, p = 0.985) and demonstrated good to excellent within-subject reproducibility (∆TTP: intraclass correlation coefficient = 0.36; correlation at aligned peaks: intraclass correlation coefficient = 0.89). CONCLUSION: This study proposes a non-invasive technique to evaluate vascular and paravascular fluid dynamics. Our findings reveal a consistent and robust cardiac pulsation-driven coupling between cerebral hemodynamics and pCSF dynamics in both younger and older adults.

Moving Toward Evidence-Based Care: Measuring Preferences in Zoo-Housed Aquatic Turtles Using 24-h Remote Monitoring.

Providing evidence-based care to animals is a common goal in zoos and aquariums. However, there are many understudied species with a lack of information available, which may result in suboptimal care for individuals of these species. Using preference tests to ask individual animals what they want can be an effective means to enhance their care, and subsequently, their welfare. Using 24-h remote monitoring, we assessed substrate, enclosure feature, and lighting preferences of five aquatic turtles (two wood turtles, one Blanding's turtle, and two spotted turtles) that share an indoor enclosure at Lincoln Park Zoo. In addition, we compared enclosure feature and lighting preferences between winter and summer to determine whether the turtles had changing seasonal preferences despite being housed indoors. We found that the wood turtles and Blanding's turtle had substrate preferences, whereas the spotted turtles did not. In addition, we found that the turtles' enclosure feature preferences were consistent between winter and summer, but the amount of time spent on land, logs, and in water varied by individual. Finally, we found that the turtles utilized areas with ambient lighting more than areas with a heat lamp or UV lamp; this was consistent between winter and summer. The turtle preferences observed in this study can contribute to the development of care strategies that support their welfare and, in turn, may inspire similar preference studies at other institutions as we collectively advance toward providing animals of all taxonomic groups with evidence-based care.

Collaborative Implementation of Robotic Surgery Into an Academic Pediatric Surgery Practice.

INTRODUCTION: Robotic surgery continues to drive evolution in minimally invasive surgery. Due to the confined operative fields encountered, pediatric surgeons may uniquely benefit from the precise control offered by robotic technologies compared to open and laparoscopic techniques. We describe a unique collaborative implementation of robotic surgery into an academic pediatric surgery practice through adult robotic surgeon partnership. We compare robotic cholecystectomy (RC) and laparoscopic cholecystectomy (LC) outcomes, hypothesizing that RC will be equivalent to LC in key quality outcomes. METHODS: We evaluate 14 mo of systems development and training, and 24 mo of collaborative operative experience evoking a purposeful tiered case progression, establishing core robotic competencies, prior to advancing operative complexity. Univariate analyses compared LC versus RC. RESULTS: 36 robotic operations were performed in children aged 8-18 y, in a tiered progression from 24 cholecystectomies to 2 ileocecectomies, 2 paraesophageal hernia repairs, 1 anterior rectopexy, 1 spleen-preserving distal pancreatectomy, 1 Heller myotomy, 1 choledochal cyst resection with roux-en-y hepaticojejunostomy, 1 median arcuate ligament release, and 1 thoracic esophageal duplication cyst resection. For LC and RC, there were no significant differences in procedure duration, discharge opioids, hospital readmission, or rates of surgical site infection or bile duct injury. CONCLUSIONS: Robotic surgery has potential to significantly enhance pediatric surgery. RC appears equivalent to LC but presents multiple additional theoretical benefits in pediatric patients. Our pilot program experience supports the feasibility and safety of pediatric robotic surgery. We emphasize the importance of a stepwise progression in operative difficulty and collaboration with adult robotic surgery experts.

Performance of a Tic Screening Tool (MOVeIT) in Comparison to Expert Clinician Assessment in a Developmental-Behavioral Pediatrics Clinic Sample.

Youth with intellectual and developmental disabilities typically have higher rates of tics and stereotypies compared to children with otherwise typical development. Differentiating between these two pediatric movement disorders can be challenging due to overlapping clinical features, but is relevant due to distinct treatment modalities. The current study evaluated sensitivity and specificity of a tic screening measure, the Motor or Vocal Inventory of Tics (MOVeIT) in a pediatric sample enriched for stereotypy and tics. Children (n=199, age 2-15 years old) receiving care in a developmental-behavioral pediatrics clinic underwent a gold-standard diagnostic assessment by a tic expert; these evaluations were compared to the MOVeIT. The MOVeIT demonstrated good sensitivity (89.8%) and relatively lower specificity (57.1%) compared to tic expert for detecting tics in the overall sample. Specificity of the MOVeIT to identify tics improved to 75% when excluding children with co-occurring stereotypy. For children with tics and co-occurring stereotypy, sensitivity remained high (91.9%) but specificity was low (39.1%). The area under the curve (AUC) value to detect tics on the MOVeIT compared to the tic expert gold standard was significantly higher for children without stereotypy (AUC=85.7%) than those with stereotypy (AUC=64.3%, p <0.01). Overall, the ability to detect tics was better in those without co-occurring stereotypy symptoms. Further work is needed to establish the utility of the MOVeIT in populations where there is a high likelihood of co-occurring tics and stereotypy and in general population settings. Accurate distinction between tics and stereotypy will guide choices for intervention and anticipatory guidance for families.

Virtual Compared With In-Office Postoperative Visits After Urogynecologic Surgery: A Randomized Controlled Trial.

OBJECTIVE: To compare patient satisfaction, health care resource utilization, and adverse events among patients receiving a virtual video compared with in-office postoperative visit after urogynecologic surgery. We hypothesized that virtual video visits would be noninferior to in-office visits. METHODS: This was a randomized noninferiority clinical trial of patients undergoing surgery for pelvic organ prolapse and urinary incontinence at a single academic tertiary referral center. Participants were randomized to receive either a virtual video postoperative visit or a standard in-office postoperative visit. The primary outcome was patient satisfaction measured by the validated PSQ-18 (Patient Satisfaction Questionnaire-18) (noninferiority margin 5 points) at the 6-week postoperative visit. Secondary outcomes included PSQ-18 domain scores (noninferiority margin 0.5 points) and composite health care resource utilization and adverse events after the 6-week postoperative visit up to 12 weeks after surgery (noninferiority margin 10%). A sample size of 100 participants (50 per group) would allow 80% power to assess a 5-point noninferiority margin on the total PSQ-18 with an SD of 10 and α=0.05. RESULTS: From January 2023 to September 2023, 265 patients were screened for eligibility, and 104 were randomized. A total of 100 participants (50 per arm) completed the study and were included in the analysis. The mean±SD age of all participants was 57.0±13.2 years. The mean±SD PSQ-18 total score was 75.18±8.15 in the virtual group and 75.14±8.7 in the in-office group. The mean PSQ-18 total score was 0.04 points higher (ie, greater degree of satisfaction) in the virtual group, with a 95% CI of -2.75 to 2.83, which met the criterion for noninferiority. Between-group differences for all PSQ-18 domain scores likewise met criterion for noninferiority. Composite health care resource utilization was 14.0% lower in the virtual group than in the in-office group (20.0% vs 34.0%, 95% CI, -28.0% to 1.0%). For composite adverse events, the between-group difference was 2.0% (2.0% in virtual group vs 0.0% in in-office group, 95% CI,-3.0% to 8.0%). CONCLUSION: Virtual video postoperative visits were noninferior to in-office visits with regard to patient satisfaction, health care resource utilization, and adverse events and can be offered as an alternative to in-office visits for postoperative follow-up after urogynecologic surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT05641077.

Population genetic structure and demographic history reconstruction of introduced flathead catfish (Pylodictis olivaris) in two US Mid-Atlantic rivers.

Population genetic analysis of invasive populations can provide valuable insights into the source of introductions, pathways for expansion, and their demographic histories. Flathead catfish (Pylodictis olivaris) are a prolific invasive species with high fecundity, long-distance dispersal, and piscivorous feeding habits that can lead to declines in native fish populations. In this study, we analyse the genetics of invasive P. olivaris in the Mid-Atlantic region to assess their connectivity and attempt to reconstruct the history of introduced populations. Based on an assessment across 13 microsatellite loci, P. olivaris from the Susquehanna River system (N = 537), Schuylkill River (N = 33), and Delaware River (N = 1) have low genetic diversity (global Hobs = 0.504), although we detected no evidence of substantial inbreeding (FIS = -0.083 to 0.022). P. olivaris from these different river systems were genetically distinct, suggesting separate introductions. However, population structure was much weaker within each river system and exhibited a pattern of high connectivity, with some evidence of isolation by distance. P. olivaris from the Susquehanna and Schuylkill rivers showed evidence for recent genetic bottlenecks, and demographic models were consistent with historical records, which suggest that populations were established by recent founder events consisting of a small number of individuals. Our results show the risk posed by small introductions of P. olivaris, which can spread widely once a population is established, and highlight the importance of prevention and sensitive early detection methods to prevent the spread of P. olivaris in the future.

Descriptive epidemiology and phylogenetic analysis of highly pathogenic avian influenza H5N1 clade 2.3.4.4b in British Columbia (B.C.) and the Yukon, Canada, September 2022 to June 2023.

Surveillance data from wildlife and poultry was used to describe the spread of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in British Columbia (B.C.) and the Yukon, Canada from September 2022 - June 2023 compared to the first 'wave' of the outbreak in this region, which occurred April - August 2022, after the initial viral introduction. Although the number of HPAI-positive poultry farms and wildlife samples was greater in 'Wave 2', cases were more tightly clustered in southwestern B.C. and the most commonly affected species differed, likely due to an influx of overwintering waterfowl in the area. Eight HPAI genetic clusters, representing seven genotypes and two inter-continental viral incursions, were detected, with significant variation in the relative abundance of each cluster between the waves. Phylogenetic data suggests multiple spillover events from wild birds to poultry and mammals but could not rule out transmission among farms and among mammals.

Human Orthohantavirus disease prevalence and genotype distribution in the U.S., 2008-2020: a retrospective observational study.

Background: In the United States (U.S.), hantavirus pulmonary syndrome (HPS) and non-HPS hantavirus infection are nationally notifiable diseases. Criteria for identifying human cases are based on clinical symptoms (HPS or non-HPS) and acute diagnostic results (IgM+, rising IgG+ titers, RT-PCR+, or immunohistochemistry (IHC)+). Here we provide an overview of diagnostic testing and summarize human Hantavirus disease occurrence and genotype distribution in the U.S. from 2008 to 2020. Methods: Epidemiological data from the national hantavirus registry was merged with laboratory diagnostic testing results performed at the CDC. Residual hantavirus-positive specimens were sequenced, and the available epidemiological and genetic data sets were linked to conduct a genomic epidemiological study of hantavirus disease in the U.S. Findings: From 1993 to 2020, 833 human hantavirus cases have been identified, and from 2008 to 2020, 335 human cases have occurred. Among New World (NW) hantavirus cases detected at the CDC diagnostic laboratory (representing 29.2% of total cases), most (85.0%) were detected during acute disease, however, some convalescent cases were detected in states not traditionally associated with hantavirus infections (Connecticut, Missouri, New Jersey, Pennsylvania, Tennessee, and Vermont). From 1993 to 2020, 94.9% (745/785) of U.S. hantaviruses cases were detected west of the Mississippi with 45.7% (359/785) in the Four Corners region of the U.S. From 2008 to 2020, 67.7% of NW hantavirus cases were detected between the months of March and August. Sequencing of RT-PCR-positive cases demonstrates a geographic separation of Orthohantavirus sinnombreense species [Sin Nombre virus (SNV), New York virus, and Monongahela virus]; however, there is a large gap in viral sequence data from the Northwestern and Central U.S. Finally, these data indicate that commercial IgM assays are not concordant with CDC-developed assays, and that "concordant positive" (i.e., commercial IgM+ and CDC IgM+ results) specimens exhibit clinical characteristics of hantavirus disease. Interpretation: Hantaviral disease is broadly distributed in the contiguous U.S, viral variants are localised to specific geographic regions, and hantaviral disease infrequently detected in most Southeastern states. Discordant results between two diagnostic detection methods highlight the need for an improved standardised testing plan in the U.S. Hantavirus surveillance and detection will continue to improve with clearly defined, systematic reporting methods, as well as explicit guidelines for clinical characterization and diagnostic criteria. Funding: This work was funded by core funds provided to the Viral Special Pathogens Branch at CDC.

The Coronavirus Pandemic and Mental Health Presentations of Young Children.

Children under the age of four are emotionally vulnerable to global disasters, such as the COVID-19 pandemic given the lack of socialization opportunities and coping mechanisms, and susceptibility to heightened caregiver stress. Currently, the extent to which the pandemic impacted the mental health of clinically referred young children is unknown. To evaluate how children's mental health outcomes were impacted during the pandemic, interRAI Early Years assessments (N = 1343) were obtained from 11 agencies across the Province of Ontario, during pre-pandemic and pandemic timepoints. Findings demonstrated that the number of completed assessments declined during the pandemic. Further, children's emotional concerns differed before and during the pandemic, whereby children exhibited greater emotional dysregulation during the pandemic. However, there were no significant differences when examining caregiver distress, parenting strengths, child distractibility/inattention or behavioural issues. Implications for young children and their families, clinicians, and policy makers are discussed.

Association between nurses' personal, professional and work characteristics, and engagement in hospital-based clinical research.

PURPOSE: The purpose of this study was to assess the associations between demographic, professional and other personal nurse characteristics, social support factors and comfort in conducting research with nurses' level of active participation in clinical research. DESIGN: A prospective, cross-sectional, correlational design was used. METHODS: Clinical nurses working in a multihospital healthcare system were recruited by email to complete an anonymous survey that used multiple valid and reliable scales to assess demographic and professional work characteristics, curiosity, grit, locus of control, perceived social support (for research activities), comfort in conducting research, and level of being research-active. Univariate and multivariable analyses were completed. RESULTS: Of 310 participants, 274 (88.4%) were female and mean (SD) age was 42.9 (13.1) years. After condensing 11 levels of research activity to four categories, 179 (57.7%) were not research-active, and 91 (29.4%), 26 (8.3%) and 14 (4.5%) were engaged at low, moderate, and high levels, respectively. Of 78 factors, 69 (88.5%) were associated with being research-active in univariate analyses. In multivariable analysis that adjusted for age, personal experience as a patient, years as a nurse and hours in direct patient care, professionalism characteristics, higher curiosity, internal locus of control, grit perseverance, support of a nurse scientist and nurse friends, and comfort in conducting research remained associated with higher levels of being research-active (all p < 0.01). CONCLUSION: Research-active nurses were more likely to be engaged professionally in hospital-based activities beyond their work roles and displayed higher levels of positive psychological characteristics and mentorship that supported research capacity. CLINICAL RELEVANCE: Research-active nurses were more likely to have internal factors and external resources that promoted higher levels of being research-active. A strong professional governance model may enhance clinical nurses research activities.

Comparative analysis of GPT-4-based ChatGPT's diagnostic performance with radiologists using real-world radiology reports of brain tumors.

OBJECTIVES: Large language models like GPT-4 have demonstrated potential for diagnosis in radiology. Previous studies investigating this potential primarily utilized quizzes from academic journals. This study aimed to assess the diagnostic capabilities of GPT-4-based Chat Generative Pre-trained Transformer (ChatGPT) using actual clinical radiology reports of brain tumors and compare its performance with that of neuroradiologists and general radiologists. METHODS: We collected brain MRI reports written in Japanese from preoperative brain tumor patients at two institutions from January 2017 to December 2021. The MRI reports were translated into English by radiologists. GPT-4 and five radiologists were presented with the same textual findings from the reports and asked to suggest differential and final diagnoses. The pathological diagnosis of the excised tumor served as the ground truth. McNemar's test and Fisher's exact test were used for statistical analysis. RESULTS: In a study analyzing 150 radiological reports, GPT-4 achieved a final diagnostic accuracy of 73%, while radiologists' accuracy ranged from 65 to 79%. GPT-4's final diagnostic accuracy using reports from neuroradiologists was higher at 80%, compared to 60% using those from general radiologists. In the realm of differential diagnoses, GPT-4's accuracy was 94%, while radiologists' fell between 73 and 89%. Notably, for these differential diagnoses, GPT-4's accuracy remained consistent whether reports were from neuroradiologists or general radiologists. CONCLUSION: GPT-4 exhibited good diagnostic capability, comparable to neuroradiologists in differentiating brain tumors from MRI reports. GPT-4 can be a second opinion for neuroradiologists on final diagnoses and a guidance tool for general radiologists and residents. CLINICAL RELEVANCE STATEMENT: This study evaluated GPT-4-based ChatGPT's diagnostic capabilities using real-world clinical MRI reports from brain tumor cases, revealing that its accuracy in interpreting brain tumors from MRI findings is competitive with radiologists. KEY POINTS: We investigated the diagnostic accuracy of GPT-4 using real-world clinical MRI reports of brain tumors. GPT-4 achieved final and differential diagnostic accuracy that is comparable with neuroradiologists. GPT-4 has the potential to improve the diagnostic process in clinical radiology.

Cosmetic Gynecology: Is There Enough Exposure in the Obstetrics and Gynecology Residency?

Introduction  While cosmetic gynecology has gained popularity, the training experience for obstetrics and gynecology residents in this area is limited and not standardized. The primary objective was to investigate the exposure of obstetrics and gynecology residents to cosmetic gynecologic procedures including hymenoplasty, labia majora reduction, vaginoplasty, G-spot amplification, labiaplasty, clitoral hood reduction, and vaginal laser therapy. The secondary objective was to assess their comfort in performing the procedures after graduation. Methods  This is a non-validated cross-sectional survey of obstetrics and gynecology residents and their exposure to cosmetic gynecology procedures. Using the Fellowship and Residency Electronic Interactive Database Access System, the Accreditation Council for Graduate Medical Education-accredited Obstetrics and Gynecology residency programs in the United States were identified, and the residency program coordinators were asked to distribute the survey. Data regarding demographics, program-specific characteristics, and exposure to certain cosmetic gynecology procedures were obtained and reviewed. Participants' reported comfort with the independent practice of certain cosmetic gynecology procedures after graduation was also obtained. Descriptive statistics were completed. Results  A total of 96 responses were received. Approximately 50% of participants were exposed to cosmetic gynecology during training. Moreover, 70.9% of residents disagreed that they would feel confident in defining the included procedures. Furthermore, 87.5% disagreed that they would feel comfortable performing the procedures independently. A minority of participants were also unsure of the indication for cosmetic gynecology procedures, with 15.4%, 7.1%, 5.7%, and 4% unaware of the surgical indication for hymenoplasty, vaginoplasty, labiaplasty, and labia majora reduction, respectively. No participant knew the indication of surgery for vaginal laser therapy or clitoral hood reduction. Conclusions  In the setting of current cosmetic gynecology training, nearly 90% of residents were not comfortable with these surgeries after graduation. Exposure to cosmetic gynecology for obstetrics and gynecology residents was limited. Without adequate exposure, residents may face difficulty performing procedures and managing complications after graduation. Therefore, standardizing resident training for cosmetic gynecology should be considered.

Alzheimer's and metabolism wed with IDO1.

Kynurenine pathway inhibition reverses deficits in Alzheimer's mouse models.

Exploratory Dual PET imaging of [18F] fluorodeoxyglucose and [11C]acetoacetate in type 2 diabetic nonhuman primates.

Despite recent advancements in imaging (amyloid-PET & tau-PET) and fluid (Aß42/Aß40 & Aß42/ptau) biomarkers, the current standard for in vivo assessment of AD, diagnosis and prediction of Alzheimer's disease (AD) remains challenging. We demonstrated in nonhuman primates (NHP) that increased plasma and cerebrospinal fluid (CSF) glucose correlated with decreased CSF Aß42 and CSF Aß40, a hallmark of plaque promoting pathogenesis. Together, our findings demonstrate that altered glucose homeostasis and insulin resistance are associated with Aß and amyloid in rodent and NHP models. This warranted further exploration into the dynamics of altered brain metabolism in the NHP model of T2D, cross referenced with CSF and blood-based AD markers. Preliminary dual PET ([11C]acetoacetate ([11C]AcAc) and [18F]fluorodeoxyglucose ([18F]FDG) imaging studies were conducted in an aged cohort of NHPs classified as T2D (n = 5) and pre-diabetic (n = 1) along with corresponding plasma and CSF samples for metabolite analysis. [11C]AcAc and [18F]FDG PET brain standard uptake values (SUV) were highly positively associated (r = 0.88, p = 0.02) in the T2D and pre-diabetic NHPs. Age was not significantly associated with brain SUV (age range 16.5-23.5 years old). Metabolic measures were positively correlated with brain [18F]FDG and CSF Aß42:40 was positively correlated to fasting glucose values. Although our findings suggest moderate correlations, this study further elucidates that peripheral insulin resistance and poor glycemia control alter AD-related pathology, illustrating how T2D is a risk factor for AD.

The impact of non- and anthracycline-based chemotherapy on fatigue in breast cancer survivors: results from WF-97415.

PURPOSE: To examine the differential effect of non- and anthracycline-based chemotherapy on fatigue over 12 months post-diagnosis among breast cancer survivors. METHODS: This study is based on a prospective Wake Forest NCI Community Oncology Research Program (NCORP) multicenter cohort study (WF-97415) of women with stage I to III breast cancer and non-cancer controls. Analyses compared those: 1) receiving, or 2) not receiving anthracycline chemotherapy, 3) receiving aromatase inhibitors (AIs) without chemotherapy, with 4) a comparator group without a history of cancer. In-person clinic assessments were conducted at: baseline (prior to chemotherapy or start of AI therapy), and 3 and 12 months after baseline. The Functional Assessment of Chronic Illness Therapy-Fatigue scale was the primary outcome. Estimated least squares means by group using mixed models with a random subject effect, fixed effects of time and group, and the interaction between time and group was used to compare groups across time, controlling for age, comorbidities, and treatment variables. RESULTS: Among 284 women (mean age = 53.4 years, sd 11.9 years), there was a significant (p < 0.0001) group by time interaction, with a sharp increase in fatigue at 3 months in the two chemotherapy groups in comparison to the non-chemotherapy and non-cancer controls. The two chemotherapy groups did not significantly differ in fatigue at any time point. CONCLUSION: Women with breast cancer who receive non- or anthracycline-based chemotherapy experience similar trends in and levels of fatigue within the first year of treatment and greater fatigue than women receiving AIs alone or women without breast cancer.

Cocaine disrupts action flexibility via glucocorticoid receptors.

Many addictive drugs increase stress hormone levels. They also alter the propensity of organisms to prospectively select actions based on long-term consequences. We hypothesized that cocaine causes inflexible action by increasing circulating stress hormone levels, activating the glucocorticoid receptor (GR). We trained mice to generate two nose pokes for food and then required them to update action-consequence associations when one response was no longer reinforced. Cocaine delivered in adolescence or adulthood impaired the capacity of mice to update action strategies, and inhibiting CORT synthesis rescued action flexibility. Next, we reduced Nr3c1, encoding GR, in the orbitofrontal cortex (OFC), a region of the brain responsible for interlacing new information into established routines. Nr3c1 silencing preserved action flexibility and dendritic spine abundance on excitatory neurons, despite cocaine. Spines are often considered substrates for learning and memory, leading to the discovery that cocaine degrades the representation of new action memories, obstructing action flexibility.

ChatGPT's diagnostic performance based on textual vs. visual information compared to radiologists' diagnostic performance in musculoskeletal radiology.

OBJECTIVES: To compare the diagnostic accuracy of Generative Pre-trained Transformer (GPT)-4-based ChatGPT, GPT-4 with vision (GPT-4V) based ChatGPT, and radiologists in musculoskeletal radiology. MATERIALS AND METHODS: We included 106 "Test Yourself" cases from Skeletal Radiology between January 2014 and September 2023. We input the medical history and imaging findings into GPT-4-based ChatGPT and the medical history and images into GPT-4V-based ChatGPT, then both generated a diagnosis for each case. Two radiologists (a radiology resident and a board-certified radiologist) independently provided diagnoses for all cases. The diagnostic accuracy rates were determined based on the published ground truth. Chi-square tests were performed to compare the diagnostic accuracy of GPT-4-based ChatGPT, GPT-4V-based ChatGPT, and radiologists. RESULTS: GPT-4-based ChatGPT significantly outperformed GPT-4V-based ChatGPT (p < 0.001) with accuracy rates of 43% (46/106) and 8% (9/106), respectively. The radiology resident and the board-certified radiologist achieved accuracy rates of 41% (43/106) and 53% (56/106). The diagnostic accuracy of GPT-4-based ChatGPT was comparable to that of the radiology resident, but was lower than that of the board-certified radiologist although the differences were not significant (p = 0.78 and 0.22, respectively). The diagnostic accuracy of GPT-4V-based ChatGPT was significantly lower than those of both radiologists (p < 0.001 and < 0.001, respectively). CONCLUSION: GPT-4-based ChatGPT demonstrated significantly higher diagnostic accuracy than GPT-4V-based ChatGPT. While GPT-4-based ChatGPT's diagnostic performance was comparable to radiology residents, it did not reach the performance level of board-certified radiologists in musculoskeletal radiology. CLINICAL RELEVANCE STATEMENT: GPT-4-based ChatGPT outperformed GPT-4V-based ChatGPT and was comparable to radiology residents, but it did not reach the level of board-certified radiologists in musculoskeletal radiology. Radiologists should comprehend ChatGPT's current performance as a diagnostic tool for optimal utilization. KEY POINTS: This study compared the diagnostic performance of GPT-4-based ChatGPT, GPT-4V-based ChatGPT, and radiologists in musculoskeletal radiology. GPT-4-based ChatGPT was comparable to radiology residents, but did not reach the level of board-certified radiologists. When utilizing ChatGPT, it is crucial to input appropriate descriptions of imaging findings rather than the images.

Insights into the Clinical, Biological and Therapeutic Impact of Copy Number Alteration in Cancer.

Copy number alterations (CNAs), resulting from the gain or loss of genetic material from as little as 50 base pairs or as big as entire chromosome(s), have been associated with many congenital diseases, de novo syndromes and cancer. It is established that CNAs disturb the dosage of genomic regions including enhancers/promoters, long non-coding RNA and gene(s) among others, ultimately leading to an altered balance of key cellular functions. In cancer, CNAs have been associated with almost all steps of the disease: predisposition, initiation, development, maintenance, response to treatment, resistance, and relapse. Therefore, understanding how specific CNAs contribute to tumourigenesis may provide prognostic insight and ultimately lead to the development of new therapeutic approaches to improve patient outcomes. In this review, we provide a snapshot of what is currently known about CNAs and cancer, incorporating topics regarding their detection, clinical impact, origin, and nature, and discuss the integration of innovative genetic engineering strategies, to highlight the potential for targeting CNAs using novel, dosage-sensitive and less toxic therapies for CNA-driven cancer.

Association of Alzheimer's disease polygenic risk score with concussion severity and recovery metrics.

Identification of genetic alleles associated with both Alzheimer's disease (AD) and concussion severity/recovery could help explain the association between concussion and elevated dementia risk. However, there has been little investigation into whether AD risk genes associate with concussion severity/recovery, and the limited findings are mixed. We used AD polygenic risk scores (PRS) and APOE genotypes to investigate any such associations in the NCAA-DoD Grand Alliance CARE Consortium (CARE) dataset. We assessed six outcomes in 931 total participants. The outcomes were two concussion recovery measures (number of days to asymptomatic status, number of days to return to play (RTP)) and four concussion severity measures (scores on SAC and BESS, SCAT symptom severity, and total number of symptoms). We calculated PRS using a published score [1] and performed multiple linear regression (MLR) to assess the relationship of PRS with the outcomes. We also used t-tests and chi-square tests to examine outcomes by APOE genotype, and MLR to analyze outcomes in European and African genetic ancestry subgroups. Higher PRS was associated with longer injury to RTP in the normal RTP (<24 days) subgroup ( p = 0.024), and one standard deviation increase in PRS resulted in a 9.89 hour increase to the RTP interval. There were no other consistently significant effects, suggesting that high AD genetic risk is not strongly associated with more severe concussions or poor recovery in young adults. Future studies should attempt to replicate these findings in larger samples with longer follow-up using PRS calculated from diverse populations.