Examining the role of ChatGPT in the management of distal radius fractures: insights into its accuracy and consistency.

BACKGROUND: The optimal management of distal radius fractures remains a challenge for orthopaedic surgeons. The emergence of Artificial Intelligence (AI) and Large Language Models (LLMs), especially ChatGPT, affords significant potential in improving healthcare and research. This study aims to assess the accuracy and consistency of ChatGPT's knowledge in managing distal radius fractures, with a focus on its capability to provide information for patients and assist in the decision-making processes of orthopaedic clinicians. METHODS: We presented ChatGPT with seven questions on distal radius fracture management over two sessions, resulting in 14 responses. These questions covered a range of topics, including patient inquiries and orthopaedic clinical decision-making. We requested references for each response and involved two orthopaedic registrars and two senior orthopaedic surgeons to evaluate response accuracy and consistency. RESULTS: All 14 responses contained a mix of both correct and incorrect information. Among the 47 cited references, 13% were accurate, 28% appeared to be fabricated, 57% were incorrect, and 2% were correct but deemed inappropriate. Consistency was observed in 71% of the responses. CONCLUSION: ChatGPT demonstrates significant limitations in accuracy and consistency when providing information on distal radius fractures. In its current format, it offers limited utility for patient education and clinical decision-making.

Clonal Lineage Tracing with Somatic Delivery of Recordable Barcodes Reveals Migration Histories of Metastatic Prostate Cancer.

The patterns by which primary tumors spread to metastatic sites remain poorly understood. Here, we define patterns of metastatic seeding in prostate cancer (PCa) using a novel injection-based mouse model - EvoCaP (Evolution in Cancer of the Prostate), featuring aggressive metastatic cancer to bone, liver, lungs, and lymph nodes. To define migration histories between primary and metastatic sites, we used our EvoTraceR pipeline to track distinct tumor clones containing recordable barcodes. We detected widespread intratumoral heterogeneity from the primary tumor in metastatic seeding, with few clonal populations (CPs) instigating most migration. Metastasis-to-metastasis seeding was uncommon, as most cells remained confined within the tissue. Migration patterns in our model were congruent with human PCa seeding topologies. Our findings support the view of metastatic PCa as a systemic disease driven by waves of aggressive clones expanding their niche, infrequently overcoming constraints that otherwise keep them confined in the primary or metastatic site.

Tricuspid Regurgitation in Patients With Heart Failure and Preserved Ejection Fraction: JACC State-of-the-Art Review.

Heart failure with preserved ejection fraction (HFpEF) is associated with high morbidity and mortality. Important risk factors for the development of HFpEF are similar to risk factors for the progression of tricuspid regurgitation (TR), and both conditions frequently coexist and thus is a distinct phenotype or a marker for advanced HF. Many patients with severe, symptomatic atrial secondary TR have been enrolled in current transcatheter device trials, and may represent patients at an advanced stage of HFpEF. Management of HFpEF thus may affect the pathophysiology of TR, and the physiologic changes that occur following transcatheter treatment of TR, may also impact symptoms and outcomes in patients with HFpEF. This review discusses these issues and suggests possible management strategies for these patients.

Benign Etiology for High-Risk Intraductal Papillary Mucinous Neoplasm: A Case Report and Literature Review.

Intraductal papillary mucinous neoplasms are relatively common and entail a variable risk of malignant potential. The Fukuoka guidelines present criteria for the risk of malignant transformation and are used for risk stratification and treatment decision-making. However, these guidelines entail some fallibility with limited sensitivity and specificity. In this case, we present an individual who had many of the hallmarks of malignant transformation but was found to have no evidence of malignancy or high-grade dysplasia. We discuss the suspected etiology of this individual's condition and how it might arise in others, as well as a brief review of the literature on risk factors in intraductal papillary mucinous neoplasms.

An evidence-based screening tool for heart failure with preserved ejection fraction: the HFpEF-ABA score.

Heart failure with preserved ejection fraction (HFpEF) is under-recognized in clinical practice. Although a previously developed risk score, termed H2FPEF, can be used to estimate HFpEF probability, this score requires imaging data, which is often unavailable. Here we sought to develop an HFpEF screening model that is based exclusively on clinical variables and that can guide the need for echocardiography and further testing. In a derivation cohort (n = 414, 249 women), a clinical model using age, body mass index and history of atrial fibrillation (termed the HFpEF-ABA score) showed good discrimination (area under the curve (AUC) = 0.839 (95% confidence interval (CI) = 0.800-0.877), P < 0.0001). The performance of the model was validated in an international, multicenter cohort (n = 736, 443 women; AUC = 0.813 (95% CI = 0.779-0.847), P < 0.0001) and further validated in two additional cohorts: a cohort including patients with unexplained dyspnea (n = 228, 136 women; AUC = 0.840 (95% CI = 0.782-0.900), P < 0.0001) and a cohort for which HF hospitalization was used instead of hemodynamics to establish an HFpEF diagnosis (n = 456, 272 women; AUC = 0.929 (95% CI = 0.909-0.948), P < 0.0001). Model-based probabilities were also associated with increased risk of HF hospitalization or death among patients from the Mayo Clinic (n = 790) and a US national cohort across the Veteran Affairs health system (n = 3076, 110 women). Using the HFpEF-ABA score, rapid and efficient screening for risk of undiagnosed HFpEF can be performed in patients with dyspnea using only age, body mass index and history of atrial fibrillation.

Optimizing single-cell RNA sequencing methods for human colon biopsies: droplet-based vs. picowell-based platforms.

Background & Aims: Single-cell RNA sequencing (scRNA) has empowered many insights into gastrointestinal microenvironments. However, profiling human biopsies using droplet-based scRNA (D-scRNA) is challenging since it requires immediate processing to minimize epithelial cell damage. In contrast, picowell-based (P-scRNA) platforms permit short-term frozen storage before sequencing. We compared P- and D-scRNA platforms on cells derived from human colon biopsies. Methods: Endoscopic rectosigmoid mucosal biopsies were obtained from two adults and conducted D-scRNA (10X Chromium) and P-scRNA (Honeycomb HIVE) in parallel using an individual's pool of single cells (> 10,000 cells/participant). Three experiments were performed to evaluate 1) P-scRNA with cells under specific storage conditions (immediately processed [fresh], vs. frozen at -20C vs. -80C [2 weeks]); 2) fresh P-scRNA versus fresh D-scRNA; and 3) P-scRNA stored at -80C with fresh D-scRNA. Results: Significant recovery of loaded cells was achieved for fresh (80.9%) and -80C (48.5%) P-scRNA and D-scRNA (76.6%), but not -20C P-scRNA (3.7%). However, D-scRNA captures more typeable cells among recovered cells (71.5% vs. 15.8% Fresh and 18.4% -80C P-scRNA), and these cells exhibit higher gene coverage at the expense of higher mitochondrial read fractions across most cell types. Cells profiled using D-scRNA demonstrated more consistent gene expression profiles among the same cell type than those profiled using P-scRNA. Significant intra-cell-type differences were observed in profiled gene classes across platforms. Conclusions: Our results highlight non-overlapping advantages of P-scRNA and D-scRNA and underscore the need for innovation to enable high-fidelity capture of colonic epithelial cells. The platform-specific variation highlights the challenges of maintaining rigor and reproducibility across studies that use different platforms.

antiCD49d Ab treatment ameliorates age-associated inflammatory response and mitigates CD8+ T-cell cytotoxicity after traumatic brain injury.

Patients aged 65 years and older account for an increasing proportion of patients with traumatic brain injury (TBI). Older TBI patients experience increased morbidity and mortality compared to their younger counterparts. Our prior data demonstrated that by blocking α4 integrin, anti-CD49d antibody (aCD49d Ab) abrogates CD8+ T-cell infiltration into the injured brain, improves survival, and attenuates neurocognitive deficits. Here, we aimed to uncover how aCD49d Ab treatment alters local cellular responses in the aged mouse brain. Consequently, mice incur age-associated toxic cytokine and chemokine responses long-term post-TBI. aCD49d Ab attenuates this response along with a T helper (Th)1/Th17 immunological shift and remediation of overall CD8+ T cell cytotoxicity. Furthermore, aCD49d Ab reduces CD8+ T cells exhibiting higher effector status, leading to reduced clonal expansion in aged, but not young, mouse brains with chronic TBI. Together, aCD49d Ab is a promising therapeutic strategy for treating TBI in the older people. Graphic abstract: Aged brains after TBI comprise two pools of CD8 + T cells . The aged brain has long been resided by a population of CD8 + T cells that's exhaustive and dysfunctional. Post TBI, due to BBB impairment, functional CD8 + T cells primarily migrate into the brain parenchyma. Aged, injury-associated microglia with upregulated MHC class I molecules can present neoantigens such as neuronal and/or myelin debris in the injured brains to functional CD8+ T, resulting in downstream CD8+ T cell cytotoxicity. aCD49d Ab treatment exerts its function by blocking the migration of functional effector CD8 + T cell population, leading to less cytotoxicity and resulting in improved TBI outcomes in aged mice.

Treatment of Shoulder Cartilage Defects in Athletes.

Articular cartilage defects in the glenohumeral joint may be found in laborers, the elderly, and young athletes, among others. Various factors can contribute to cartilage damage, including prior surgery, trauma, avascular necrosis, inflammatory arthritis, joint instability, and osteoarthritis. There is a wide variety of treatment options, from conservative treatment, injections, and surgical options, including arthroscopic debridement, microfracture, osteochondral autograft transfer, osteochondral graft transplantation, autologous chondrocyte implantation, and the newly emerging techniques such as biologic augmentation. There is a challenge to determine the optimal treatment options, especially for young athletes, due to limited outcomes in the literature. However, there are many options which are viable to address osteochondral defects of the glenohumeral joint.

Intersectional Oppression-Based Stress, Drinking to Cope Motives, and Alcohol Use and Hazardous Drinking Among Sexual and Gender Minority Adolescents Who Are Black, Indigenous, and People of Color.

Purpose: This study examined the associations between intersectional oppression-based stress and recent alcohol use and hazardous drinking among sexual and gender minority (SGM; e.g., queer or transgender) adolescents who were Black, Indigenous, and People of Color (BIPOC), also known as queer and transgender BIPOC (QTBIPOC) adolescents, and the mediating role of coping motives (i.e., drinking to cope) on these associations. Methods: Data were from a subsample of QTBIPOC adolescents who used alcohol in the past year (n = 1365) from a national U.S. sample of SGM adolescents aged 13-18 years. Results: Intersectional oppression-based stressors were associated with greater odds of recent alcohol use and hazardous drinking, as well as greater coping motives. Coping motives mediated the associations between intersectional-based stressors and both recent alcohol use and hazardous drinking among the aggregate sample of QTBIPOC adolescents, as well as among some subgroups of BIPOC adolescents. Conclusions: The results of this study highlight that intersectional oppression-based stressors are prevalent among QTBIPOC adolescents and serve as a risk factor for alcohol use and hazardous drinking. Multilevel interventions are needed to target and dismantle intersectional oppressions to address alcohol inequities impacting QTBIPOC adolescents. Drinking to cope motives mediated the associations between intersectional oppression-based stress and drinking outcomes, underscoring another important mechanism to target within a context of oppression in drinking interventions.

Considerations in the Diagnosis and Management of Pulmonary Hypertension Associated With Left Heart Disease.

Pulmonary hypertension associated with left heart disease (PH-LHD) remains the most common cause of pulmonary hypertension globally. Etiologies include heart failure with reduced and preserved ejection fraction and left-sided valvular heart diseases. Despite the increasing prevalence of PH-LHD, there remains a paucity of knowledge about the hemodynamic definition, diagnosis, treatment modalities, and prognosis among clinicians. Moreover, clinical trials have produced mixed results on the usefulness of pulmonary vasodilator therapies for PH-LHD. In this expert review, we have outlined the critical role of meticulous hemodynamic evaluation and provocative testing for cases of diagnostic uncertainty. Therapeutic strategies-pharmacologic, device-based, and surgical therapies used for managing PH-LHD-are also outlined. PH-LHD in advanced heart failure, and the role of mechanical circulatory support in PH-LHD is briefly explored. An in-depth understanding of PH-LHD by all clinicians is needed for improved recognition and outcomes among patients with PH-LHD.

The Association of Stigma, School, and Family Factors with Patterns of Substance Use Among LGBTQ Youth.

Polysubstance use is associated with myriad short- and long-term health outcomes. Although prior research has documented differences in polysubstance use between lesbian, gay, bisexual, transgender, queer/questioning, and other sexual and gender minoritized (LGBTQ +) youth and their heterosexual/cisgender counterparts, as well as between subgroups of LGBTQ + youth, it is unknown how personal, family, and school factors are associated with substance use patterns among LGBTQ + youth. Using a large, national sample of 9646 LGBTQ + youth ages 13-17, we used latent class analysis to examine patterns of alcohol, tobacco, and marijuana use and to determine whether personal, family, and school factors predict class membership. We identified five classes of substance use: polysubstance use, polysubstance experimentation, dual alcohol and cannabis, alcohol, and no use. Greater depression and LGBTQ + victimization, and an ability to be oneself at school, were associated with greater odds of membership in the polysubstance use class, while higher levels of family connection and having a Gender Sexuality Alliance (GSA) at school were associated with lower odds of membership in the polysubstance use class. Our analysis also revealed sociodemographic differences in class membership. These findings highlight potential mechanisms for intervention to reduce polysubstance use among LGBTQ + youth.

Targeted Therapy Innovations for Melanoma.

Melanoma, a malignant tumor of melanocytes, poses a significant clinical challenge due to its aggressive nature and high potential for metastasis. The advent of targeted therapy has revolutionized the treatment landscape of melanoma, particularly for tumors harboring specific genetic alterations such as BRAF V600E mutations. Despite the initial success of targeted agents, resistance inevitably arises, underscoring the need for novel therapeutic strategies. This review explores the latest advances in targeted therapy for melanoma, focusing on new molecular targets, combination therapies, and strategies to overcome resistance.

Detection of a Kinetically Competent Compound-I Intermediate in the Vancomycin Biosynthetic Enzyme OxyB.

Cytochrome P450 enzymes are abundantly encoded in microbial genomes. Their reactions have two general outcomes, one involving oxygen insertion via a canonical "oxygen rebound" mechanism and a second that diverts from this pathway and leads to a wide array of products, notably intramolecular oxidative cross-links. The antibiotic of-last-resort, vancomycin, contains three such cross-links, which are crucial for biological activity and are installed by the P450 enzymes OxyB, OxyA, and OxyC. The mechanisms of these enzymes have remained elusive in part because of the difficulty in spectroscopically capturing transient intermediates. Using stopped-flow UV/visible absorption and rapid freeze-quench electron paramagnetic resonance spectroscopies, we show that OxyB generates the highly reactive compound-I intermediate, which can react with a model vancomycin peptide substrate in a kinetically competent fashion to generate product. Our results have implications for the mechanism of OxyB and are in line with the notion that oxygen rebound and oxidative cross-links share early steps in their catalytic cycles.

Free Radicals in Little Cigar Mainstream Smoke and the Potential Influence of Flavoring Chemicals on Free Radical Production.

Implementation of the Tobacco Control Act in 2009 banned characterizing flavors in cigarettes (except menthol and tobacco), but substitution has occurred by the continued availability of alternative flavored products (i.e., flavored little cigars). Little is known about how flavorants in noncigarette tobacco products impact human health. Thus, we investigated the impact of flavorants on free radical production in the mainstream smoke of little cigars. Gas- and particulate-phase free radical yields in mainstream smoke generated from 12 commercial little cigar brands and research little cigars and cigarettes were measured via electron paramagnetic resonance spectroscopy using the International Organization of Standardization (ISO) smoking protocol. Flavorants were extracted from unsmoked little cigars and analyzed by gas chromatography-mass spectroscopy. Gas- and particulate-phase radical yields from little cigars ranged from 13.5 to 97.6 and 0.453-1.175 nmol/unit, respectively. Comparatively, research cigarettes yielded an average of 4.9 nmol gas-phase radicals/unit and 0.292 nmol particulate-phase radicals/unit. From the products, 66 flavorants were identified, with each brand containing 4-24 individual flavorants. The free radical content was strongly correlated with the number of flavorants present in each cigar (r = 0.74, p = 0.01), indicating that highly flavored little cigars may produce higher levels of toxic free radicals. The presence of the flavorant ethyl methylphenylglycidate (strawberry) was associated with >2-fold higher levels of GP radicals (p = 0.001). Our results show that free radical delivery from little cigars is greater than that from research cigarettes and provide empirical evidence for the harmfulness of flavored tobacco products. Additionally, it demonstrates that flavorants present in combustible tobacco products can influence the levels of free radicals produced. Therefore, future tobacco product standards should consider little cigars.

GRT-X Stimulates Dorsal Root Ganglia Axonal Growth in Culture via TSPO and Kv7.2/3 Potassium Channel Activation.

GRT-X, which targets both the mitochondrial translocator protein (TSPO) and the Kv7.2/3 (KCNQ2/3) potassium channels, has been shown to efficiently promote recovery from cervical spine injury. In the present work, we investigate the role of GRT-X and its two targets in the axonal growth of dorsal root ganglion (DRG) neurons. Neurite outgrowth was quantified in DRG explant cultures prepared from wild-type C57BL6/J and TSPO-KO mice. TSPO was pharmacologically targeted with the agonist XBD173 and the Kv7 channels with the activator ICA-27243 and the inhibitor XE991. GRT-X efficiently stimulated DRG axonal growth at 4 and 8 days after its single administration. XBD173 also promoted axonal elongation, but only after 8 days and its repeated administration. In contrast, both ICA27243 and XE991 tended to decrease axonal elongation. In dissociated DRG neuron/Schwann cell co-cultures, GRT-X upregulated the expression of genes associated with axonal growth and myelination. In the TSPO-KO DRG cultures, the stimulatory effect of GRT-X on axonal growth was completely lost. However, GRT-X and XBD173 activated neuronal and Schwann cell gene expression after TSPO knockout, indicating the presence of additional targets warranting further investigation. These findings uncover a key role of the dual mode of action of GRT-X in the axonal elongation of DRG neurons.

Advancing LGBTQ+ inclusion in STEM education and AI research.

The authors emphasize diversity, equity, and inclusion in STEM education and artificial intelligence (AI) research, focusing on LGBTQ+ representation. They discuss the challenges faced by queer scientists, educational resources, the implementation of National AI Campus, and the notion of intersectionality. The authors hope to ensure supportive and respectful engagement across all communities.

Inhomogeneous terminators on the exoplanet WASP-39 b.

Transmission spectroscopy has been a workhorse technique over the past two decades to constrain the physical and chemical properties of exoplanet atmospheres 1-5. One of its classical key assumptions is that the portion of the atmosphere it probes - the terminator region - is homogeneous. Several works in the past decade, however, have put this into question for highly irradiated, hot (Teq ≳ 1000 K) gas giant exoplanets both empirically 6-10 and via 3-dimensional modelling 11-17. While models predict clear differences between the evening (day-to-night) and morning (night-to-day) terminators, direct morning/evening transmission spectra in a wide wavelength range has not been reported for an exoplanet to date. Under the assumption of precise and accurate orbital parameters on WASP-39 b, here we report the detection of inhomogeneous terminators on the exoplanet WASP-39 b, which allows us to retrieve its morning and evening transmission spectra in the near-infrared (2 - 5 µm) using JWST. We observe larger transit depths in the evening which are, on average, 405±88 ppm larger than the morning ones, also having qualitatively larger features than the morning spectrum. The spectra are best explained by models in which the evening terminator is hotter than the morning terminator by 177 - 57 + 65 K with both terminators having C/O ratios consistent with solar. General circulation models (GCMs) predict temperature differences broadly consistent with the above value and point towards a cloudy morning terminator and a clearer evening terminator.

Absolute-judgment models better predict eyewitness decision-making than do relative-judgment models.

When presented with a lineup, the witness is tasked with identifying the culprit or indicating that the culprit is not present. The witness then qualifies the decision with a confidence judgment. But how do witnesses go about making these decisions and judgments? According to absolute-judgment models, witnesses determine which lineup member provides the strongest match to memory and base their identification decision and confidence judgment on the absolute strength of this MAX lineup member. Conversely, relative-judgment models propose that witnesses determine which lineup member provides the strongest match to memory and then base their identification decision and confidence judgment on the relative strength of the MAX lineup member compared to the remaining lineup members. We took a critical test approach to test the predictions of both models. As predicted by the absolute-judgment model, but contrary to the predictions of the relative-judgment model, witnesses were more likely to correctly reject low-similarity lineups than high-similarity lineups (Experiment 1), and more likely to reject biased lineups than fair lineups (Experiment 2). Likewise, witnesses rejected low-similarity lineups with greater confidence than high-similarity lineups (Experiment 1) and rejected biased lineups with greater confidence than fair lineups (Experiment 2). Only a single pattern was consistent with the relative model and inconsistent with the absolute model: suspect identifications from biased lineups were made with greater confidence than suspect identifications from fair lineups (Experiment 2). The results suggest that absolute-judgment models better predict witness decision-making than do relative-judgment models and that pure relative-judgment models are unviable.

The Crystal Structure of the Michaelis-Menten Complex of C1 Esterase Inhibitor and C1s Reveals Novel Insights into Complement Regulation.

The ancient arm of innate immunity known as the complement system is a blood proteolytic cascade involving dozens of membrane-bound and solution-phase components. Although many of these components serve as regulatory molecules to facilitate controlled activation of the cascade, C1 esterase inhibitor (C1-INH) is the sole canonical complement regulator belonging to a superfamily of covalent inhibitors known as serine protease inhibitors (SERPINs). In addition to its namesake role in complement regulation, C1-INH also regulates proteases of the coagulation, fibrinolysis, and contact pathways. Despite this, the structural basis for C1-INH recognition of its target proteases has remained elusive. In this study, we present the crystal structure of the Michaelis-Menten (M-M) complex of the catalytic domain of complement component C1s and the SERPIN domain of C1-INH at a limiting resolution of 3.94 Å. Analysis of the structure revealed that nearly half of the protein/protein interface is formed by residues outside of the C1-INH reactive center loop. The contribution of these residues to the affinity of the M-M complex was validated by site-directed mutagenesis using surface plasmon resonance. Parallel analysis confirmed that C1-INH-interfacing residues on C1s surface loops distal from the active site also drive affinity of the M-M complex. Detailed structural comparisons revealed differences in substrate recognition by C1s compared with C1-INH recognition and highlight the importance of exosite interactions across broader SERPIN/protease systems. Collectively, this study improves our understanding of how C1-INH regulates the classical pathway of complement, and it sheds new light on how SERPINs recognize their cognate protease targets.