Comparison of cerebral safety following atrial fibrillation using pulsed field and thermal ablation: Results of the Neurological Assessment Subgroup in the ADVENT Trial.

BACKGROUND: Atrial fibrillation (AF) ablation carries the risk of silent cerebral event (SCE) and silent cerebral lesion (SCL). Though "silent," these may have long-term clinical implications and are challenging to study as post-procedural MRI is not standard-of-care. OBJECTIVE: The neurological assessment subgroup (NAS) of ADVENT compared cerebral effects of pulsed field ablation (PFA) to standard-of-care thermal ablation. METHODS: The NAS included consecutive randomized PFA and thermal ablation patients who received post-procedural brain MRI 12-48 hours post-ablation. Patients with apparent SCE or SCL findings underwent a modified Rankin Scale (mRS) assessment. MRI images were subsequently reviewed by a blinded Brain Imaging Core Laboratory. RESULTS: In total, 77 patients with paroxysmal AF were enrolled at 6 centers; 71 had analyzable scans (34 PFA; 37 thermal ablation). Through individual center review, 6 PFA and 4 thermal scans were identified as SCE/SCL positive, of which, 3 PFA and 0 thermal SCE/SCL findings were confirmed by a blinded core laboratory. MRI findings revealed one patient with 2-4mm SCEs, one patient with a 3mm SCE, and one patient with 2 SCLs (5.5mm and 11mm). All mRS and NIHSS scores were 0 prior to discharge and at 90-day follow-up. There were only two neurological safety events (1 TIA (PFA) and 1 stroke (thermal) in the ADVENT study, neither of which was part of the NAS. CONCLUSIONS: The ADVENT trial provides the first prospective, randomized data on the cerebral impact of PFA and thermal ablation of AF. Incidence of SCE/SCLs following ablation in the NAS was low.

Exploring Native Hawaiian and Pacific Islander Youths' E-Cigarette Resistance Strategies: Implications for Tobacco Product Use Prevention.

This study examined the e-cigarette and vaping resistance strategies used by Native Hawaiian and Pacific Islander (NHPI) youths in rural Hawai'i. Focus groups (N = 17) were conducted in eight geographically dispersed elementary, middle/intermediate, and multilevel schools in low-income communities on Hawai'i Island. Sixty-nine youths (67% NHPI, Mage = 12.5 years) participated in this study. The resistance strategies discussed across the greatest number of groups were "refuse" (saying no), "explain" (providing reasons for vaping refusal), "avoid" (avoiding people or places where e-cigarettes were used), and "leave" (walking away from a situation where e-cigarettes were being used). Participants described the challenges in using these strategies within contexts characterized by widespread peer and family vaping and strong social demands to use e-cigarettes. The findings suggest the need for multi-level interventions based on youths' resistance strategies to meaningfully reduce youth vaping use in rural and/or NHPI communities.

Congenital Disseminated Malignant Rhabdoid Tumor Mimicking a Vascular Lesion.

A congenital disseminated malignant rhabdoid tumor (MRT) is an exceedingly rare and aggressive pediatric cancer marked by the presence of malignant rhabdoid cells in various organs, including the brain, kidneys, and soft tissues, at birth. It is often detected prenatally or shortly post-birth. The malignancy's aggressiveness results in a bleak prognosis, offering limited treatment options and low survival rates. Early diagnosis and comprehensive medical intervention are crucial, but managing this condition is complicated by its rarity. We herein presented a case of a 37 and 1/7 week gestation male infant with a rapidly growing arm soft tissue mass within two weeks, diagnosed as an MRT. Post-delivery examinations revealed multiple lesions in the lungs, kidney, liver, and adrenal glands. Notably, chemotherapy yielded a significant improvement in the arm lesion, contrasting with other lesions showing a limited response. This observation suggests potential tumor heterogeneity, emphasizing the necessity of diverse therapeutic regimens. Our case underscores the complexities of congenital disseminated MRT, prompting a reevaluation of treatment strategies for enhanced efficacy in managing this challenging pediatric cancer.

Performance of ChatGPT on American Board of Surgery In-Training Examination Preparation Questions.

INTRODUCTION: Chat Generative Pretrained Transformer (ChatGPT) is a large language model capable of generating human-like text. This study sought to evaluate ChatGPT's performance on Surgical Council on Resident Education (SCORE) self-assessment questions. METHODS: General surgery multiple choice questions were randomly selected from the SCORE question bank. ChatGPT (GPT-3.5, April-May 2023) evaluated questions and responses were recorded. RESULTS: ChatGPT correctly answered 123 of 200 questions (62%). ChatGPT scored lowest on biliary (2/8 questions correct, 25%), surgical critical care (3/10, 30%), general abdomen (1/3, 33%), and pancreas (1/3, 33%) topics. ChatGPT scored higher on biostatistics (4/4 correct, 100%), fluid/electrolytes/acid-base (4/4, 100%), and small intestine (8/9, 89%) questions. ChatGPT answered questions with thorough and structured support for its answers. It scored 56% on ethics questions and provided coherent explanations regarding end-of-life discussions, communication with coworkers and patients, and informed consent. For many questions answered incorrectly, ChatGPT provided cogent, yet factually incorrect descriptions, including anatomy and steps of operations. In two instances, it gave a correct explanation but chose the wrong answer. It did not answer two questions, stating it needed additional information to determine the next best step in treatment. CONCLUSIONS: ChatGPT answered 62% of SCORE questions correctly. It performed better at questions requiring standard recall but struggled with higher-level questions that required complex clinical decision making, despite providing detailed responses behind its rationale. Due to its mediocre performance on this question set and sometimes confidently-worded, yet factually inaccurate responses, caution should be used when interpreting ChatGPT's answers to general surgery questions.

30 years of youth system of care lessons learned - a qualitative study of Hawai'i's partnership with the Substance Abuse and Mental Health Services Administration.

BACKGROUND: The Hawai'i State Department of Health, Child and Adolescent Mental Health Division (CAMHD) has maintained a longstanding partnership with Substance Abuse and Mental Health Services Administration (SAMHSA) to enhance capacity and quality of community-based mental health services. The current study explored CAMHD's history of SAMHSA system of care (SOC) awards and identified common themes, lessons learned, and recommendations for future funding. METHODS: Employing a two-phase qualitative approach, the study first conducted content analysis on seven final project reports, identifying themes and lessons learned based on SOC values and principles. Subsequently, interviews were conducted with 11 system leaders in grant projects and SOC award projects within the state. All data from project reports and interview transcripts were independently coded and analyzed using rapid qualitative analysis techniques. RESULTS: Content validation and interview coding unveiled two content themes, interagency collaboration and youth and family voice, as areas that required long-term and consistent efforts across multiple projects. In addition, two general process themes, connection and continuity, emerged as essential approaches to system improvement work. The first emphasizes the importance of fostering connections in family, community, and culture, as well as within workforce members and child-serving agencies. The second highlights the importance of nurturing continuity throughout the system, from interagency collaboration to individual treatment. CONCLUSIONS: The study provides deeper understanding of system of care evaluations, offering guidance to enhance and innovate youth mental health systems. The findings suggest that aligning state policies with federal guidelines and implementing longer funding mechanisms may alleviate administrative burdens.

Reactive oxygen species promote endurance exercise-induced adaptations in skeletal muscles.

The discovery that contracting skeletal muscle generates reactive oxygen species (ROS) was first reported over 40 years ago. The prevailing view in the 1980s was that exercise-induced ROS production promotes oxidation of proteins and lipids resulting in muscle damage. However, a paradigm shift occurred in the 1990s as growing research revealed that ROS are signaling molecules, capable of activating transcriptional activators/coactivators and promoting exercise-induced muscle adaptation. Growing evidence supports the notion that reduction-oxidation (redox) signaling pathways play an important role in the muscle remodeling that occurs in response to endurance exercise training. This review examines the specific role that redox signaling plays in this endurance exercise-induced skeletal muscle adaptation. We begin with a discussion of the primary sites of ROS production in contracting muscle fibers followed by a summary of the antioxidant enzymes involved in the regulation of ROS levels in the cell. We then discuss which redox-sensitive signaling pathways promote endurance exercise-induced muscle adaptation and debate the strength of the evidence supporting the notion that redox signaling plays an essential role in muscle adaptation to endurance exercise training. In hopes of stimulating future research, we highlight several important unanswered questions in this field.

Characteristics of healthcare personnel with SARS-CoV-2 infection: 10 emerging infections program sites in the United States, April 2020-December 2021.

BACKGROUND: Understanding characteristics of healthcare personnel (HCP) with SARS-CoV-2 infection supports the development and prioritization of interventions to protect this important workforce. We report detailed characteristics of HCP who tested positive for SARS-CoV-2 from April 20, 2020 through December 31, 2021. METHODS: CDC collaborated with Emerging Infections Program sites in 10 states to interview HCP with SARS-CoV-2 infection (case-HCP) about their demographics, underlying medical conditions, healthcare roles, exposures, personal protective equipment (PPE) use, and COVID-19 vaccination status. We grouped case-HCP by healthcare role. To describe residential social vulnerability, we merged geocoded HCP residential addresses with CDC/ATSDR Social Vulnerability Index (SVI) values at the census tract level. We defined highest and lowest SVI quartiles as high and low social vulnerability, respectively. RESULTS: Our analysis included 7,531 case-HCP. Most case-HCP with roles as certified nursing assistant (CNA) (444, 61.3%), medical assistant (252, 65.3%), or home healthcare worker (HHW) (225, 59.5%) reported their race and ethnicity as either non-Hispanic Black or Hispanic. More than one third of HHWs (166, 45.2%), CNAs (283, 41.7%), and medical assistants (138, 37.9%) reported a residential address in the high social vulnerability category. The proportion of case-HCP who reported using recommended PPE at all times when caring for patients with COVID-19 was lowest among HHWs compared with other roles. CONCLUSIONS: To mitigate SARS-CoV-2 infection risk in healthcare settings, infection prevention, and control interventions should be specific to HCP roles and educational backgrounds. Additional interventions are needed to address high social vulnerability among HHWs, CNAs, and medical assistants.

Investigating flock-associated mimicry: examining the evidence for, and drivers of, plumage mimicry in the greater and lesser necklaced laughingthrush.

Visual mimicry is less understood in birds than in other taxa. The interspecific social dominance mimicry (ISDM) hypothesis asserts that subordinate species resemble dominant ones to reduce aggression. Plumage mimicry has also been consistently noted in mixed-species flocks (MSFs), suggesting a connection to grouping behaviour, although it is unclear whether this is linked to ISDM. We studied greater necklaced laughingthrush (GNLT, Pterorhinus pectoralis) and lesser necklaced laughingthrush (LNLT, Garrulax monileger), which were recently placed in different genera. Measurements of 162 museum specimens showed LNLT converging in sympatry with GNLT in necklace colour, but diverging in necklace to body ratio, with proportionally smaller necklaces. The species were closely associated in six of seven MSF systems from Nepal to China. In a study of foraging behaviour in Nepal, aggression was rare between the species, LNLT followed GNLT and had lower foraging rates when further from GNLT. Our data suggest a link between this MSF-associated mimicry and ISDM, and that the subordinate LNLT may be the mimic and gain more from the resemblance. The species spend much time together in dense and poorly lit vegetation, where the LNLTs resemblance to GNLTs potentially allows them to forage closer to GNLTs than would be otherwise possible.

Contribution of tumour and immune cells to PD-L1 expression as a predictive biomarker in metastatic triple-negative breast cancer: exploratory analysis from KEYNOTE-119.

The efficacy of pembrolizumab monotherapy versus chemotherapy increased with increasing programmed death ligand 1 (PD-L1) expression, as quantified by combined positive score (CPS; PD-L1 expression on both tumour cells and immune cells) in patients with previously treated metastatic triple-negative breast cancer (mTNBC) in the phase 3 KEYNOTE-119 study. This exploratory analysis was conducted to determine whether the expression of PD-L1 on tumour cells contributes to the predictive value of PD-L1 CPS in mTNBC. PD-L1 expression in tumour samples was assessed using PD-L1 IHC 22C3 pharmDx and quantified using both CPS and tumour proportion score (TPS; PD-L1 expression on tumour cells alone). Calculated immune cell density (CID) was defined as CPS minus TPS. The ability of each scoring method (CPS, TPS, and CID) to predict clinical outcomes with pembrolizumab was evaluated. With pembrolizumab, the area under the receiver operating characteristic curve was 0.69 (95% CI = 0.58-0.80) for CPS, 0.55 (95% CI = 0.46-0.64) for TPS, and 0.67 (95% CI = 0.56-0.77) for CID. After correction for cutoff prevalence, CPS performed as well as, if not better than, CID with respect to predicting objective response rate, progression-free survival, and overall survival. Data from this exploratory analysis suggest that, although PD-L1 expression on immune cells alone is predictive of response to programmed death 1 blockade in mTNBC, adding tumour PD-L1 expression assessment (i.e. CPS, which combines immune cell and tumour cell PD-L1 expression) may improve prediction. PD-L1 CPS thus remains an effective and broadly applicable uniform scoring system for enriching response to programmed death 1 blockade with pembrolizumab in mTNBC as well as other tumour types.

Characteristics of Patients With Initial Clostridioides difficile Infection (CDI) That Are Associated With Increased Risk of Multiple CDI Recurrences.

Background: Because interventions are available to prevent further recurrence in patients with recurrent Clostridioides difficile infection (rCDI), we identified predictors of multiple rCDI (mrCDI) in adults at the time of presentation with initial CDI (iCDI). Methods: iCDI was defined as a positive C difficile test in any clinical setting during January 2018-August 2019 in a person aged ≥18 years with no known prior positive test. rCDI was defined as a positive test ≥14 days from the previous positive test within 180 days after iCDI; mrCDI was defined as ≥2 rCDI. We performed multivariable logistic regression analysis. Results: Of 18 829 patients with iCDI, 882 (4.7%) had mrCDI; 437 with mrCDI and 7484 without mrCDI had full chart reviews. A higher proportion of patients with mrCDI than without mrCDI were aged ≥65 years (57.2% vs 40.7%; P < .0001) and had healthcare (59.1% vs 46.9%; P < .0001) and antibiotic (77.3% vs 67.3%; P < .0001) exposures in the 12 weeks preceding iCDI. In multivariable analysis, age ≥65 years (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.55-2.35), chronic hemodialysis (aOR, 2.28; 95% CI, 1.48-3.51), hospitalization (aOR, 1.64; 95% CI, 1.33-2.01), and nitrofurantoin use (aOR, 1.95; 95% CI, 1.18-3.23) in the 12 weeks preceding iCDI were associated with mrCDI. Conclusions: Patients with iCDI who are older, on hemodialysis, or had recent hospitalization or nitrofurantoin use had increased risk of mrCDI and may benefit from early use of adjunctive therapy to prevent mrCDI. If confirmed, these findings could aid in clinical decision making and interventional study designs.

Evaluation of association between center colorectal neuroendocrine neoplasm volume and survival among patients with colorectal neuroendocrine carcinoma.

BACKGROUND: Although correlation between center volume and survival has been reported for several complex cancers, it remains unknown if this is true for colorectal neuroendocrine carcinomas (CRNECs). We hypothesized that higher center annual volume of colorectal neuroendocrine neoplasm resections would be associated with overall survival (OS) for patients with CRNECs. METHODS: Patients in the National Cancer Database diagnosed with stages I-III CRNEC between 2006 and 2018 and who underwent surgical resection were identified. The mean annual colorectal neuroendocrine neoplasm resection volume threshold associated with significantly worse mortality hazard was determined using restricted cubic splines. Kaplan-Meier (KM) method was used to compare OS, while Cox proportional hazards model was used for multivariable analysis. RESULTS: There were 694 patients with CRNEC who met inclusion criteria across 1229 centers. Based on the cubic spline, centers treating fewer than one colorectal neuroendocrine neoplasm patient every 3 years on average had worse outcomes. Centers below this threshold were classified as low-volume (LV) centers corresponding with 42% of centers and about 15% of the patient cohort. In unadjusted survival analysis, LV patients had a median OS of 14 months (95% confidence interval [CI]: 10-19) while those treated at HV centers had a median OS of 33 months (95% CI: 25-49). In multivariable analysis, resection at a LV center was associated with increased risk of mortality (1.42 [95% CI: 1.01-2.00], p = 0.04). CONCLUSION: CRNEC patients have a dire prognosis; however, treatment at an HV center may be associated with decreased risk of mortality.

Aluminothermic reduction of CeO2: mechanism of an economical route to aluminum-cerium alloys.

Cerium oxide is a low-value byproduct of rare-earth mining yet constitutes the largest fraction of the rare earth elements. The reduction of cerium oxide by liquid aluminum is proposed as an energy- and cost-efficient route to produce high-strength Al-Ce alloys. This work investigated the mechanism of a multi-step reduction reaction to facilitate the industrial adaptation of the process. Differential scanning calorimetry in combination with time-resolved synchrotron diffraction data uncovered the rate-limiting reaction step as the origin of the reported temperature dependence of reduction efficiency. This is the first in situ study of a metallothermic reaction mechanism and will serve as guidance for cost- and energy efficient industrial process control.

Role of Diagnostic Laparoscopy During Pancreatic Cancer Surgery in the Modern Era.

INTRODUCTION: Despite improvements in preoperative image resolution, approximately 10% of curative-intent resection attempts for pancreatic ductal adenocarcinoma are aborted at the time of operation. To avoid nontherapeutic laparotomy, many surgeons perform intraoperative diagnostic laparoscopy (DL) to identify radiographically occult metastatic disease. There are no consensus guidelines regarding DL in pancreatic cancer. The goal of this study is to investigate the efficacy of same-procedure DL at avoiding nontherapeutic laparotomy. METHODS: A single-institution retrospective review was performed from 2016 to 2022, identifying 196 patients with pancreatic ductal adenocarcinoma who were taken to the operating room for open curative-intent resection. Patient demographic, tumor characteristic, treatment, and outcome data were abstracted. Univariate and multivariate Cox hazard ratio analysis was performed to investigate risk factors for overall survival and recurrence-free survival. Number needed to treat (NNT) was calculated to identify number of DLs necessary to avoid one nontherapeutic laparotomy. RESULTS: Curative-intent resection was achieved in 161 (82.1%) patients. One hundred twenty six (64.0%) patients received DL prior to resection and DL identified metastatic disease in three (2.4%) patients with an NNT of 42. NNT of DL in a subgroup analysis performed on clinically high-risk patients (defined by preoperative or preneoadjuvant therapy carbohydrate antigen 19-9 > 500 U/mL) is 11. Receipt of DL did not prolong operative times in patients receiving pancreaticoduodenectomy when accounting for completed versus aborted resection. CONCLUSIONS: Although intraoperative DL is a short procedure with minimal morbidity, these data demonstrate that same-procedure DL has potential efficacy in avoiding nontherapeutic laparotomy only in a subgroup of clinically high-risk patients. Focus should remain on optimizing preoperative patient selection and further investigating novel diagnostic markers predictive of occult metastatic disease.

Art therapy masks reflect emotional changes in military personnel with PTSS.

Among disabling post-traumatic stress symptoms (PTSS) are irritability, aggressive behavior, distressing memories and general impaired cognition and negative mood. Art therapy interventions, including mask-making, can potentially alleviate these symptoms. We tested the hypothesis that art conveys emotions and predicted that blinded viewers would be able to perceive changes in theoretically derived emotional profiles expressed in art made by military personnel with PTSS from the onset to the end of therapy. Five service members and veterans exhibiting PTSS were enrolled in an 8-session art therapy protocol, during which they artistically transformed papier-mâché masks at the beginning and end of the protocol. We found that blinded viewers without knowledge of the masks' creation stage (onset or end of therapy) read initial masks as conveying more negative emotions (e.g., angry, upset, and challenged) and later masks as conveying more positive emotions (calm and pleasure). Based on the assessments from the blinded evaluators, we infer the emotional transition experienced by the participants was expressed in the masks. In an exploratory arm of the study, we also found that viewers were better able to empathize with the negative emotions experienced by participants with PTSS when asked to explicitly take their perspective.

Implementation of a high-resolution, high-contrast magnetic resonance imaging protocol with extended delayed phases for peritoneal mesothelioma.

Background: Imaging of peritoneal malignancies using conventional cross-sectional imaging is challenging, but accurate assessment of peritoneal disease burden could guide better selection for definitive surgery. Here we demonstrate feasibility of high-resolution, high-contrast magnetic resonance imaging (MRI) of peritoneal mesothelioma and explore optimal timing for delayed post-contrast imaging. Methods: Prospective data from inpatients with malignant peritoneal mesothelioma (MPM), imaged with a novel MRI protocol, were analyzed. The new sequences augmenting the clinical protocol were (I) pre-contrast coronal high-resolution T2-weighted single-shot fast spin echo (COR hr T2w SSH FSE) of abdomen and pelvis; and (II) post-contrast coronal high-resolution three-dimensional (3D) T1-weighted modified Dixon (COR hr T1w mDIXON) of abdomen, acquired at five delay times, up to 20 min after administration of a double dose of contrast agent. Quantitative analysis of contrast enhancement was performed using linear regression applied to normalized signal in lesion regions of interest (ROIs). Qualitative analysis was performed by three blinded radiologists. Results: MRI exams from 14 participants (age: mean ± standard deviation, 60±12 years; 71% male) were analyzed. The rate of lesion contrast enhancement was strongly correlated with tumor grade (cumulative nuclear score) (r=-0.65, P<0.02), with 'early' delayed phase (12 min post-contrast) and 'late' delayed phase (19 min post-contrast) performing better for higher grade and lower grade tumors, respectively, in agreement with qualitative scoring of image contrast. Conclusions: High-resolution, high-contrast MRI with extended post-contrast imaging is a viable modality for imaging peritoneal mesothelioma. Multiple, extended (up to 20 min post-contrast) delayed phases are necessary for optimal imaging of peritoneal mesothelioma, depending on the grade of disease.

Addressing Biological Questions with Preclinical Cancer Imaging.

The broad application of noninvasive imaging has transformed preclinical cancer research, providing a powerful means to measure dynamic processes in living animals. While imaging technologies are routinely used to monitor tumor growth in model systems, their greatest potential lies in their ability to answer fundamental biological questions. Here we present the broad range of potential imaging applications according to the needs of a cancer biologist with a focus on some of the common biological processes that can be used to visualize and measure. Topics include imaging metastasis; biophysical properties such as perfusion, diffusion, oxygenation, and stiffness; imaging the immune system and tumor microenvironment; and imaging tumor metabolism. We also discuss the general ability of each approach and the level of training needed to both acquire and analyze images. The overall goal is to provide a practical guide for cancer biologists interested in answering biological questions with preclinical imaging technologies.

Coherent charge hopping suppresses photoexcited small polarons in ErFeO3 by antiadiabatic formation mechanism.

Polarons are prevalent in condensed matter systems with strong electron-phonon coupling. The adiabaticity of the polaron relates to its transport properties and spatial extent. To date, only adiabatic small polaron formation has been measured following photoexcitation. The lattice reorganization energy is large enough that the first electron-optical phonon scattering event creates a small polaron without requiring substantial carrier thermalization. We measure that frustrating the iron-centered octahedra in the rare-earth orthoferrite ErFeO3 leads to antiadiabatic polaron formation. Coherent charge hopping between neighboring Fe3+─Fe2+ sites is measured with transient extreme ultraviolet spectroscopy and lasts several picoseconds before the polaron forms. The resulting small polaron formation time is an order of magnitude longer than previous measurements and indicates a shallow potential well, even in the excited state. The results emphasize the importance of considering dynamic electron-electron correlations, not just electron-phonon-induced lattice changes, for small polarons for transport, catalysis, and photoexcited applications.

Zebrafish raptor mutation inhibits the activity of mTORC1, inducing craniofacial defects due to autophagy-induced neural crest cell death.

The mechanistic target of rapamycin (mTOR) coordinates metabolism and cell growth with environmental inputs. mTOR forms two functional complexes: mTORC1 and mTORC2. Proper development requires both complexes but mTORC1 has unique roles in numerous cellular processes, including cell growth, survival and autophagy. Here, we investigate the function of mTORC1 in craniofacial development. We created a zebrafish raptor mutant via CRISPR/Cas9, to specifically disrupt mTORC1. The entire craniofacial skeleton and eyes were reduced in size in mutants; however, overall body length and developmental timing were not affected. The craniofacial phenotype associates with decreased chondrocyte size and increased neural crest cell death. We found that autophagy is elevated in raptor mutants. Chemical inhibition of autophagy reduced cell death and improved craniofacial phenotypes in raptor mutants. Genetic inhibition of autophagy, via mutation of the autophagy gene atg7, improved facial phenotypes in atg7;raptor double mutants, relative to raptor single mutants. We conclude that finely regulated levels of autophagy, via mTORC1, are crucial for craniofacial development.