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The use of toothbrushes has significantly improved oral hygiene. However, if brushing of the teeth is not done judiciously, it could result in severe trauma to the soft tissues of the oral cavity. This is particularly true in the young age group, since children tend to be very playful while brushing their teeth. This article describes the case report of a child who sustained a penetrating injury while brushing his teeth. A detailed plan for the management of such injuries is also presented.

An evaporated Al layer is known as an excellent rear metallization for highly efficient solar cells, but suffers from incompatibility with a common solder process. To enable solar cellinterconnection and module integration, in this work the Al layer is complemented with a solder stack of TiN/Ti/Ag or TiN/NiV/Ag, in which the TiN layer acts as an Al diffusion barrier. X-ray photoelectron spectroscopy measurements prove that diffusion of Al through the stack and the formation of an Al2O3 layer on the stack's surface are responsible for a loss of solderability after a strong post-metallization anneal, which is often mandatory to improve contact resistance and passivation quality. An optimization of the reactive TiN sputter process results in a densification of the TiN layer, which improves its barrier quality against Al diffusion. However, measurements with Xray diffraction and scanning electron microscopy show that small grains with vertical grain boundaries persist, which still offer fast diffusion paths. Therefore, the concept of stuffing is introduced. By incorporating oxygen into the grain boundaries of the sputtered TiN layer, Al diffusion is strongly reduced as confirmed by secondary ion mass spectroscopy profiles. A quantitative analysis reveals a one order of magnitude lower Al diffusion coefficient for stuffed TiN layers. This metallization system maintains its solderability even after strong post-metallization annealing at 425 °C for 15 min. This paper thus presents an industrially feasible, conventionally solderable, and longterm stable metallization scheme for highly efficient silicon solar cells. [ABSTRACT FROM AUTHOR]

The aim of this study was to understand the variability in the fronts and water masses, and the effect of melt water on the concentration of chlorophyll (Chla) in the Indian Ocean sector of the Southern Ocean using hydrographic data collected during the austral summer (February 2010 and 2011). The Southern Subtropical Front (SSTF) and Northern Sub Antarctic Front (SAF1) were found to be further south at 57°30′E than at 47–48°E. This southward shift of the fronts was consistent with the southward meandering (c. 2°) of the Antarctic Circumpolar Current (ACC) core from the western section to the eastern section, which could have been caused by the bottom topography. The intrusion of water masses also differed between the western and eastern transects of the study region as a result of the meandering of the ACC core. Fresh water layer thickness relative to the winter water in 2011 was more compared to that during 2010. This could have been due to the larger amount of sea ice that was present in the winter of 2010, which subsequently melted, resulting in the advection of melt water from the south and west of the study region. In situ observations and satellite data detected a high Chlaconcentration (c. 0.38 mg m−3) south of the Northern Polar Front (PF1) in 2011, which was caused by this melt water. [ABSTRACT FROM AUTHOR]

This study examined the pathological complete response (pCR) rate and safety of sequential gemcitabine-based combinations in breast cancer. We also examined gene expression profiles from tumour biopsies to identify biomarkers predictive of response. Indian women with large or locally advanced breast cancer received 4 cycles of gemcitabine 1200 mg m(-2) plus doxorubicin 60 mg m(-2) (Gem+Dox), then 4 cycles of gemcitabine 1000 mg m(-2) plus cisplatin 70 mg m(-2) (Gem+Cis), and surgery. Three alternate dosing sequences were used during cycle 1 to examine dynamic changes in molecular profiles. Of 65 women treated, 13 (24.5% of 53 patients with surgery) had a pCR and 22 (33.8%) had a complete clinical response. Patients administered Gem d1, 8 and Dox d2 in cycle 1 (20 of 65) reported more toxicities, with G3/4 neutropenic infection/febrile neutropenia (7 of 20) as the most common cycle-1 event. Four drug-related deaths occurred. In 46 of 65 patients, 10-fold cross validated supervised analyses identified gene expression patterns that predicted with >or=73% accuracy (1) clinical complete response after eight cycles, (2) overall clinical complete response, and (3) pCR. This regimen shows strong activity. Patients receiving Gem d1, 8 and Dox d2 experienced unacceptable toxicity, whereas patients on other sequences had manageable safety profiles. Gene expression patterns may predict benefit from gemcitabine-containing neoadjuvant therapy. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to explore the value of patient self-report assessment in heart transplant candidacy evaluation, utilizing the Millon Behavioral Health Inventory (MBHI). Patient's MBHI measures were related to important pretransplant patient characteristics and posttransplant measures of health behavior, medical morbidity, and mortality.Method: Ninety heart patients with end-stage cardiac disease completed the MBHI during pretransplant candidacy evaluations, and also were interviewed concerning their coping effectiveness, support resources, and compliance history. Postransplant follow-up of 61 living and 29 deceased patients included measures of survival time, postsurgical medical care, rejection and infection episodes, and nurse ratings of medication compliance and problematic interpersonal health behaviors.Results: The MBHI coping scales were found to significantly discriminate good and poor pretransplant compliance, and interview judgments of good and poor coping and support resources, with modest accuracy. The MBHI also was superior to these interview judgments in predicting posttransplant survival time and medical care used. Certain scales were also positively associated with physical parameters of pretransplant and posttransplant status.Conclusions: Patient self-report with the MBHI can contribute to identification of patients at risk for a problematic outcome with transplant, by providing information pertinent to clinical decision making and outcome management analysis with this special population of cardiac patients. [ABSTRACT FROM AUTHOR]

We simulate a densely jammed, athermal assembly of repulsive soft particles immersed in a solvent. Starting from an initial condition corresponding to a quench from a high temperature, we find nontrivial slow dynamics driven by a gradual release of stored elastic energy, with the root mean squared particle speed decaying as a power law in time with a fractional exponent. This decay is accompanied by the presence within the assembly of spatially localized and temporally intermittent "hot spots" of nonaffine deformation, connected by long-ranged swirls in the velocity field, reminiscent of the local plastic events and long-ranged elastic propagation that have been intensively studied in sheared amorphous materials. The pattern of hot spots progressively coarsens, with the hot-spot size and separation slowly growing over time, and the associated correlation length in particle speed increasing as a sublinear power law. Each individual spot, however, exists only transiently within an overall picture of strongly intermittent dynamics. [ABSTRACT FROM AUTHOR]

It has recently been argued that steady-state vorticity bands cannot arise in shear thickening suspensions because the normal stress imbalance across the interface between the bands will set up particle migrations. In this Letter, we develop a simple continuum model that couples shear thickening to particle migration. We show by linear stability analysis that homogeneous flow is unstable towards vorticity banding, as expected, in the regime of negative constitutive slope. In full nonlinear computations, we show, however, that the resulting vorticity bands are unsteady, with spatiotemporal patterns governed by stress-concentration coupling. We furthermore show that these dynamical bands also arise in direct particle simulations, in good agreement with the continuum model. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) is rapidly being introduced into the clinical workflow of many specialties. Despite the need to train physicians who understand the utility and implications of AI and mitigate a growing skills gap, no established consensus exists on how to best introduce AI concepts to medical students during preclinical training. This study examined the effectiveness of a pilot Digital Health Scholars (DHS) non-credit enrichment elective that paralleled the Dartmouth Geisel School of Medicine's first-year preclinical curriculum with a focus on introducing AI algorithms and their applications in the concurrently occurring systems-blocks. From September 2022 to March 2023, ten self-selected first-year students enrolled in the elective curriculum run in parallel with four existing curricular blocks (Immunology, Hematology, Cardiology, and Pulmonology). Each DHS block consisted of a journal club, a live-coding demonstration, and an integration session led by a researcher in that field. Students' confidence in explaining the content objectives (high-level knowledge, implications, and limitations of AI) was measured before and after each block and compared using Mann-Whitney U tests. Students reported significant increases in confidence in describing the content objectives after all four blocks (Immunology: U  = 4.5, p  = 0.030; Hematology: U  = 1.0, p  = 0.009; Cardiology: U  = 4.0, p  = 0.019; Pulmonology: U  = 4.0, p  = 0.030) as well as an average overall satisfaction level of 4.29/5 in rating the curriculum content. Our study demonstrates that a digital health enrichment elective that runs in parallel to an institution's preclinical curriculum and embeds AI concepts into relevant clinical topics can enhance students' confidence in describing the content objectives that pertain to high-level algorithmic understanding, implications, and limitations of the studied models. Building on this elective curricular design, further studies with a larger enrollment can help determine the most effective approach in preparing future physicians for the AI-enhanced clinical workflow.

Objective: This study aims to evaluate the application and effectiveness of fractal analysis (FA) in assessing temporomandibular joint disorders (TMDs) with dental imaging., Methods: This systematic review, conducted in adherence to PRISMA-P and Cochrane Handbook guidelines, involved a comprehensive search of five electronic indexed databases up to September 15, 2024. The thorough search aimed to ensure the inclusion of all relevant studies on dental imaging with fractal dimension (FD) analysis for TMDs. The risk of bias was performed using the revised QUADAS 2 tool., Results: Out of 342 studies retrieved, 15 met the inclusion criteria and were included in the systematic review. These studies comprised 7 retrospective and 8 prospective nonrandomized clinical studies. Various imaging modalities were used including panoramic, CT, CBCT, and MRI. Most studies reported significantly lower FD values in TMD patients than in controls suggesting FD analysis' potential for detecting early TMJ degenerative changes. However, a few studies did not find significant differences or lacked control groups, highlighting the variability in findings across the research. The overall risk of bias was high regarding the applicability of all included studies., Conclusion: The fractal dimension (FD) analysis of dental images shows potential as a valuable tool for detecting early degenerative changes in temporomandibular disorders (TMDs). It could enhance diagnostic efficiency by providing additional insights from routine radiographs. However, the variability in findings and methodologies underscores the need for further research to validate and standardize these techniques., Competing Interests: Declarations. Conflict of interest: The authors declare that there is no conflict of interest. Ethics approval: No ethical approval is required. The study was registered in PROSPERO. Informed consent: Not applicable., (© 2024. The Author(s) under exclusive licence to Japanese Society for Oral and Maxillofacial Radiology.)

Background: Artificial intelligence (AI) enabled tools have been proposed as 1 solution to improve health care delivery. However, research on downstream effects of AI integration into the clinical workflow is lacking., Objective: We aim to analyze how integration of an automated basal cell carcinoma detection and tumor mapping algorithm in a Mohs micrographic surgery unit impacts the work efficiency of clinical and laboratory staff., Methods: Slide, staff, and histotechnician waiting times were analyzed over a 20-day period in a Mohs micrographic surgery unit. A simulated AI workflow was created and the time differences between the real and simulated workflows were compared., Results: Simulated nonautonomous algorithm integration led to savings of 35.6% of slide waiting time, 18.4% of staff waiting time, and 18.6% of histotechnician waiting time per day. Algorithm integration on days with increased reconstruction complexity resulted in the greatest time savings., Limitations: One Mohs micrographic surgery unit was analyzed and simulated AI integration was performed retrospectively., Conclusions: AI integration results in reduced staff waiting times, enabling increased productivity and a streamlined clinical workflow. Schedules containing surgical cases with either increased repair complexity or numerous tumor removal stages stand to benefit most. However, significant logistical challenges must be addressed before broad adoption into clinical practice is realistic., Competing Interests: None disclosed., (© 2024 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

A common application for intraoral scanners is the digitization of the morphology of teeth and palatal rugae. Palatal scans are most commonly required to fabricate complete dentures and immediate transitional dentures and serve as a reference point for assessing orthodontic results. However, they are also frequently included by accident, even though the main purpose of intraoral scanning is to reconstruct dentition using computer-aided manufacturing (CAM). The literature shows that the identification of disaster victims has frequently involved palatal rugae impressions. As the skull provides sound insulation, the rugae are resistant to heat, chemicals, and stress. Antemortem data might be difficult to find during a forensic inquiry, particularly in disaster victim identification cases. In contrast with DNA and fingerprints, there is a greater likelihood of having a dental record that contains palatal scans. With specialized software, the scans can be exported as open stereolithography (STL) files. Considering that a full case consumes up to about 100 MB of hard drive space, long-term storage should not be an issue compared to a plaster model. Additionally, dentists widely use online databases to exchange data for smile design, implant registration, and orthodontic purposes. This will produce a digital database that grows quickly and is readily usable for forensic investigations. The uniqueness of forensic features is frequently challenged; however, palatal morphology's unique trait could make it possible as it is characteristic of individuals as well as the most distinguishing factor. This review will highlight how rugae, palatal morphology, mirroring, superimposition, and geometrics can serve in forensic identification.

The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p < 0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRAS G12R had a similar OS (median 34 months), while patients with KRAS Q61 and KRAS G12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2-3.0, p = 0.006] and 22 months [HR: 1.7, 95% CI 1.3-2.3, p < 0.001], respectively). There was enrichment of KRAS G12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2-2.4, p = 0.001) and enrichment of KRAS G12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05-2.99, p = 0.04). Similar findings were observed in the external validation cohort (PanCAN's Know Your Tumor® dataset, n = 408)., (© 2024. The Author(s).)

The formation of large interstellar molecules starting from small reactants constitutes the bottom-up approach in astrochemistry. An experimental setup wherein the ionic reactant is prepared and allowed to react with neutral reactants within a confined interaction space is most desirable for this approach. Here, we present our efforts in constructing a 22-pole radio-frequency ion trap experimental setup that could act as a reaction chamber for the neutral reactant and trapped ions. A compact piezo-based pulsed supersonic expansion discharge source was developed to achieve efficient production of anions, particularly metal-bearing ions. In addition, two other ion sources, namely, the electron impact ion source and the plasma supersonic discharge ion source, were developed to cater to the production of specific ions. The geometry of this experimental setup facilitates photo excitation of trapped ions. The trapping efficiency was studied by trapping SF5+ and SF6- for a few seconds. The control exhibited by various parameters on the efficiency of the trapping is discussed in detail. Potential studies that could be performed with this new experimental setup are also discussed., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: To determine if circulating tumor DNA (ct-DNA) dynamics of epidermal growth factor receptor (EGFR) mutation in plasma can identify a subset of patients with EGFR-mutant (EGFR- m) non-small cell lung cancer (NSCLC) with inferior survival outcomes, we analyzed and compared survival outcomes among patients with and without baseline presence and early clearance of EGFR ct-DNA in plasma., Material and Methods: For 66 patients newly dia-gnosed with EGFR- m NSCLC, plasma samples were collected at baseline and 1st response assessment at 12-24 weeks for extraction of ct-DNA. Estimation of ct-DNA (EGFR exons 18, 19, 20 and 21) was done using droplet digital polymerase chain reaction (dd-PCR) on the QX200 ddPCR system (BioRad, USA). Patients with detectable EGFR ct-DNA at baseline (sample 1), with either undetectable or persistent detectable ct-DNA in sample 2 were classified as clearers and non-clearers, respectively., Results: Fifty-three patients received 1st/ 2nd generation EGFR tyrosine kinase inhibitors (TKIs) and 13 received either 3rd generation TKI (osimertinib) or chemotherapy plus gefitinib. The baseline ct-DNA-positive group had more patients with extra thoracic disease (60.4 vs. 48.5%). For the entire cohort, there was no difference in median progression-free survival (PFS) among baseline ct-DNA-negative (13.57 months) vs. ct-DNA-positive patients (12.32 months) (HR 0.74). There was a significant improvement of PFS among early ct-DNA clearers vs. non-clearers (12.32 vs. 9.92 months; HR 0.57). For those treated with 1st/ 2nd generation EGFR TKIs, this improvement in median PFS among early ct-DNA clearers vs. non-clearers was more apparent (11.76 vs. 6.8 months; HR 0.34)., Conclusions: Baseline detection of the presence of ct-DNA of EGFR mutation in plasma was not predictive of first-line PFS, but is associated with extra thoracic disease. Patients with EGFR mutation and persistence of ct-DNA at first follow-up have worse PFS and overall survival (OS) in comparison to those clearing the same in plasma, especially among those treated with 1st/ 2nd generation EGFR TKIs.

Intraoperative margin analysis is crucial for the successful removal of cutaneous squamous cell carcinomas (cSCC). Artificial intelligence technologies (AI) have previously demonstrated potential for facilitating rapid and complete tumour removal using intraoperative margin assessment for basal cell carcinoma. However, the varied morphologies of cSCC present challenges for AI margin assessment. The aim of this study was to develop and evaluate the accuracy of an AI algorithm for real-time histologic margin analysis of cSCC. To do this, a retrospective cohort study was conducted using frozen cSCC section slides. These slides were scanned and annotated, delineating benign tissue structures, inflammation and tumour to develop an AI algorithm for real-time margin analysis. A convolutional neural network workflow was used to extract histomorphological features predictive of cSCC. This algorithm demonstrated proof of concept for identifying cSCC with high accuracy, highlighting the potential for integration of AI into the surgical workflow. Incorporation of AI algorithms may improve efficiency and completeness of real-time margin assessment for cSCC removal, particularly in cases of moderately and poorly differentiated tumours/neoplasms. Further algorithmic improvement incorporating surrounding tissue context is necessary to remain sensitive to the unique epidermal landscape of well-differentiated tumours, and to map tumours to their original anatomical position/orientation., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

1The relationship between the acute effects of psychedelics and their persisting neurobiological and psychological effects is poorly understood. Here, we tracked brain changes with longitudinal precision functional mapping in healthy adults before, during, and for up to 3 weeks after oral psilocybin and methylphenidate (17 MRI visits per participant) and again 6+ months later. Psilocybin disrupted connectivity across cortical networks and subcortical structures, producing more than 3-fold greater acute changes in functional networks than methylphenidate. These changes were driven by desynchronization of brain activity across spatial scales (area, network, whole brain). Psilocybin-driven desynchronization was observed across association cortex but strongest in the default mode network (DMN), which is connected to the anterior hippocampus and thought to create our sense of self. Performing a perceptual task reduced psilocybin-induced network changes, suggesting a neurobiological basis for grounding , connecting with physical reality during psychedelic therapy. The acute brain effects of psilocybin are consistent with distortions of space-time and the self. Psilocybin induced persistent decrease in functional connectivity between the anterior hippocampus and cortex (and DMN in particular), lasting for weeks but normalizing after 6 months. Persistent suppression of hippocampal-DMN connectivity represents a candidate neuroanatomical and mechanistic correlate for psilocybin's pro-plasticity and anti-depressant effects., Competing Interests: 4.1 Conflicts of Interest Author JSS is an employee of Sumitomo Pharma America and has received consulting fees from Forbes Manhattan. Author CLR serves as a consultant to Usona Institute and Novartis and receives research support from the Tiny Blue Dot Foundation. Author GEN has received research support from Usona Institute (drug only). She has served as a paid consultant for IngenioRx, Alkermes, Inc., Sunovion Pharmaceuticals, Inc., and Novartis Pharmaceuticals Corp. NUFD is a co-founder of Turing Medical Inc, has financial interest, and may benefit financially if the company is successful in marketing FIRMM motion monitoring software products. NUFD may receive royalty income based on FIRMM technology developed at Washington University School of Medicine and licensed to Turing Medical Inc. These potential conflicts of interest have been reviewed and are managed by Washington University School of Medicine. The other authors declare no competing interests. All authors report no financial interest in psychedelics companies.

The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 PDAC patients (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p<0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRAS G12R had a similar OS (median 34 months), while patients with KRAS Q61 and KRAS G12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2-3.0, p=0.006] and 22 months [HR: 1.7, 95% CI 1.3-2.3, p<0.001], respectively). There was enrichment of KRAS G12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2-2.4, p=0.001) and enrichment of KRAS G12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05-2.99, p=0.04). Similar findings were observed in the external validation cohort (PanCAN's Know Your Tumor ® dataset, n=408)., Competing Interests: Additional Declarations: There is a conflict of interest Dan Zhao is an advisory board member for Affini-T and she has clinical trial contract with CARsgen and Mirati. Disclosures and Competing interests: This data has not been previously presented. COI disclosures pending from authors.

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer (mCRC), published in late 2022, were adapted in December 2022, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with mCRC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with mCRC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian countries. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with mCRC across the different countries of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation, coupled with a disparity in the drug approvals and reimbursement strategies, between the different countries., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: Intraoperative margin analysis is crucial for the successful removal of cutaneous squamous cell carcinomas (cSCC). Artificial intelligence technologies (AI) have previously demonstrated potential for facilitating rapid and complete tumor removal using intraoperative margin assessment for basal cell carcinoma. However, the varied morphologies of cSCC present challenges for AI margin assessment., Objective: To develop and evaluate the accuracy of an AI algorithm for real-time histologic margin analysis of cSCC., Design: A retrospective cohort study was conducted using frozen cSCC section slides and adjacent tissues., Setting: This study was conducted in a tertiary care academic center., Participants: Patients undergoing Mohs micrographic surgery for cSCC between January and March 2020., Exposures: Frozen section slides were scanned and annotated, delineating benign tissue structures, inflammation, and tumor to develop an AI algorithm for real-time margin analysis. Patients were stratified by tumor differentiation status. Epithelial tissues including epidermis and hair follicles were annotated for moderate-well to well differentiated cSCC tumors. A convolutional neural network workflow was used to extract histomorphological features predictive of cSCC at 50-micron resolution., Main Outcomes and Measures: The performance of the AI algorithm in identifying cSCC at 50-micron resolution was reported using the area under the receiver operating characteristic curve. Accuracy was also reported by tumor differentiation status and by delineation of cSCC from epidermis. Model performance using histomorphological features alone was compared to architectural features (i.e., tissue context) for well-differentiated tumors., Results: The AI algorithm demonstrated proof of concept for identifying cSCC with high accuracy. Accuracy differed by differentiation status, driven by challenges in separating cSCC from epidermis using histomorphological features alone for well-differentiated tumors. Consideration of broader tissue context through architectural features improved the ability to delineate tumor from epidermis., Conclusions and Relevance: Incorporating AI into the surgical workflow may improve efficiency and completeness of real-time margin assessment for cSCC removal, particularly in cases of moderately and poorly differentiated tumors/neoplasms. Further algorithmic improvement is necessary to remain sensitive to the unique epidermal landscape of well-differentiated tumors, and to map tumors to their original anatomical position/orientation. Future studies should assess the efficiency improvements and cost benefits and address other confounding pathologies such as inflammation and nuclei., Funding Sources: JL is supported by NIH grants R24GM141194, P20GM104416 and P20GM130454. Support for this work was also provided by the Prouty Dartmouth Cancer Center development funds., Key Points: Question: How can the efficiency and accuracy of real-time intraoperative margin analysis for the removal of cutaneous squamous cell carcinoma (cSCC) be improved, and how can tumor differentiation be incorporated into this approach? Findings: A proof-of-concept deep learning algorithm was trained, validated, and tested on frozen section whole slide images (WSI) for a retrospective cohort of cSCC cases, demonstrating high accuracy in identifying cSCC and related pathologies. Histomorphology alone was found to be insufficient to delineate tumor from epidermis in histologic identification of well-differentiated cSCC. Incorporation of surrounding tissue architecture and shape improved the ability to delineate tumor from normal tissue. Meaning: Integrating artificial intelligence into surgical procedures has the potential to enhance the thoroughness and efficiency of intraoperative margin analysis for cSCC removal. However, accurately accounting for the epidermal tissue based on the tumor's differentiation status requires specialized algorithms that consider the surrounding tissue context. To meaningfully integrate AI algorithms into clinical practice, further algorithmic refinement is needed, as well as the mapping of tumors to their original surgical site, and evaluation of the cost and efficacy of these approaches to address existing bottlenecks.

A boy in his middle childhood with severe haemophilia reported with facial swelling following dental treatment for a carious upper primary molar done at a private dental clinic elsewhere. On presentation, he had a large, tense and tender swelling of the left cheek and a haematoma on the buccal mucosa adjacent to the treated tooth. The child was found to have a low haemoglobin level. He was taken for an emergency procedure under general anaesthesia for dental extraction with incision and drainage, and simultaneously underwent packed cells and factor replacement. He recovered in the ward postoperatively with no complications and with a gradual reduction of the swelling. This report highlights the importance of caries prevention in children, especially those with haemophilia. They need to be educated about restricting cariogenic foods in their diet and maintaining good oral hygiene. Management of such patients should be carefully coordinated to minimise undesirable outcomes., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Amplification of 3q is the most common genetic alteration identified in squamous cell carcinoma of the lung (LUSC), with the most frequent amplified region being 3q26 to 3q28., Methods: In this analysis, we aim to describe the prognostic relevance of 3q amplification by focusing on a minimal common region (MCR) of amplification constituted of 25 genes. We analyzed 511 cases of LUSC from The Cancer Genome Atlas and included 476 in the final analysis., Results: We identified a 25-gene MCR that was amplified in 221 (44.3%) cases and was associated with better disease-specific survival (not reported [NR] versus 9.25 y, 95% confidence interval [CI]: 5.24-NR, log-rank p  = 0.011) and a progression-free interval of 8 years (95% CI: 5.1-NR) versus 4.9 years (95% CI: 3.5-NR, log-rank p  = 0.020). Multivariable analysis revealed that MCR amplification was associated with improved disease-specific survival and progression-free interval., Conclusions: Amplification of the 25-gene MCR within 3q was present in 44% of this cohort, consisting mainly of Caucasian patients with early stage LUSC. This analysis strongly indicates the prognostic relevance of the 25-gene MCR within 3q. We are further evaluating its prognostic and predictive relevance in a racially diverse patient population with advanced LUSC., (© 2023 The Authors.)

Background: Ectopic Cushing syndrome (EAS) secondary to an adrenocorticotropin hormone (ACTH)-releasing neuroendocrine tumor (NET) is a rare diagnosis that can be resistant to standard treatments. Abiraterone acetate (AA) is a selective and irreversible inhibitor of 17α-hydroxylase/17,20-lyase that blocks adrenal steroidogenesis, including cortisol synthesis. In this case, we present the novel use of AA in treating malignant EAS by blocking cortisol synthesis., Case Description: We present a case in which a middle-aged female diagnosed with EAS secondary to metastatic ACTH-releasing NET who presented with progressively worsening weakness, diagnosed with glucocorticoid-induced myopathy associated with autonomic dysregulation. Due to her tenuous clinical status, the patient was not a candidate for any invasive procedures. She was treated with AA which led to a rapid quantitative reduction in the serum cortisol levels and hemodynamic improvement. This temporizing measure allowed for clinical stability, the patient underwent adrenal artery embolization and abiraterone was discontinued. The patient did not experience any further decline in her strength, her symptoms related to myopathy slowly improved, she was discharged to a rehabilitation facility., Conclusions: This case illustrates how the inhibition of cortisol caused by AA can be effectively used in the management of EAS. The potent and rapid effects of AA in blocking endogenous cortisol production may be considered as a temporizing measure in the treatment of malignant EAS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-376/coif). RL has received consulting honoraria from Xcenda and Aptitude health in the past 36 months. The other authors have no conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

Major depressive disorder during pregnancy can be detrimental to the fetus and patient. Treatments can include electroconvulsive therapy (ECT) for severe cases. The use of ketamine in ECT can provide symptomatic relief as well as induce anesthesia. Here, we describe the case of a 35-year-old gravid woman with a long-standing history of major depressive disorder who presented with treatment-resistant depression with suicidal ideation after an alteration in her antidepressant medication. After psychiatric evaluation, she was deemed to be a good candidate for ECT augmented with ketamine for symptomatic relief. This was complicated by an positive but asymptomatic COVID-19 status. Despite these factors, the patient experienced significant relief after an eight-treatment course of ECT, with a reduction of her PHQ-9 score from 22/27 to 4/27 points., (Copyright © 2022 Baylor University Medical Center.)

Large granular lymphocytic (LGL) leukemia is a rare chronic lymphoproliferative disorder that can arise from T- or natural killer-cell lineages. It is an indolent disease that typically occurs in the sixth decade of life. Most cases of T-cell LGL leukemia (T-LGL) are associated with autoimmune disorders. Patients with T-LGL are generally asymptomatic; however, they can present with symptoms related to neutropenia, infections, and autoimmune disorders. Here, we report two cases of T-LGL in which the patients presented with liver dysfunction., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Abu Rous et al.)

Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia and an elevated level of serum parathyroid hormone. PHPT leads to hypercalcemia and presents with renal, skeletal, and neuropsychiatric symptoms. Neuropsychiatric manifestations of PHPT such as psychotic, depressive, and anxiety disorders are rare. Delirium may also be present in patients with PHPT. Parathyroidectomy is the treatment of choice for patients with physically symptomatic PHPT, but it remains unclear if parathyroidectomy is indicated for its psychiatric manifestations. It is unclear if parathyroidectomy should be performed as a treatment for medication-refractory psychiatric symptoms or deferred until psychiatric symptoms have been better controlled. We present two cases of hyperparathyroidism (HPT)-associated hypercalcemia-one with lithium-associated HPT-in which psychiatric manifestations resolved with parathyroidectomy., (Copyright © 2022 Baylor University Medical Center.)

Background: Since the World Health Organization declared coronavirus disease (COVID-19) as a pandemic, most countries started treating their patients with various therapies. However, the data regarding their safety and effectiveness is still lacking., Objectives: We aimed to evaluate the adverse drug reactions (ADRs) incidence and their predisposing factors among COVID-19 patients., Methods: A retrospective observational study that was conducted at a tertiary academic hospital from March - June 2020. Patients were included if they were ≥ 18 years old, inpatient, had a reverse transcriptase-polymerase chain reaction (PCR) positive for COVID-19, and were treated with; (lopinavir-ritonavir, hydroxychloroquine, chloroquine, favipiravir, ribavirin, or interferon-ß) either as monotherapy or combination therapy for three days or longer. The data of eligible patients were retrieved from the electronic medical records. A standardized data collection form was designed to collect patient demographics, COVID-19 severity based on the Saudi Ministry of Health management protocols, antiviral therapies, duration of therapy, and length of stay (LOS). The ADRs were identified via conducting a comprehensive review using predefined triggers and were evaluated using Naranjo Score., Results: A total of 155 patients were included of which 123 (79.4%) were males. In our sample, the incidence proportion of ADRs per patient was 72.3%. A total of 287 ADRs were identified most of them were hepatic (n =  101 , 35.2%), gastrointestinal (n =  59 , 20.6%), hematological (n =  47 , 16%), and endocrine (n =  45 , 15%). Hydroxychloroquine was the most common drug associated with ADRs (n =  155 ). The length of stay (10 - 20 days) was the only statistically significant with the ADR incidence (p-value = 0.008; 95 %CI 1.216:3.568)., Conclusions: The ADRs are prevalent among COVID-19 patients, which assure the importance of implementing active hospital-based pharmacovigilance systems., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Leaflet durability and costs restrict contemporary trans-catheter aortic valve replacement (TAVR) largely to elderly patients in affluent countries. TAVR that are easily deployable, avoid secondary procedures and are also suitable for younger patients and non-calcific aortic regurgitation (AR) would significantly expand their global reach. Recognizing the reduced need for post-implantation pacemakers in balloon-expandable (BE) TAVR and the recent advances with potentially superior leaflet materials, a trans-catheter BE-system was developed that allows tactile, non-occlusive deployment without rapid pacing, direct attachment of both bioprosthetic and polymer leaflets onto a shape-stabilized scallop and anchorage achieved by plastic deformation even in the absence of calcification. Three sizes were developed from nickel-cobalt-chromium MP35N alloy tubes: Small/23 mm, Medium/26 mm and Large/29 mm. Crimp-diameters of valves with both bioprosthetic (sandwich-crosslinked decellularized pericardium) and polymer leaflets (triblock polyurethane combining siloxane and carbonate segments) match those of modern clinically used BE TAVR. Balloon expansion favors the wing-structures of the stent thereby creating supra-annular anchors whose diameter exceeds the outer diameter at the waist level by a quarter. In the pulse duplicator, polymer and bioprosthetic TAVR showed equivalent fluid dynamics with excellent EOA, pressure gradients and regurgitation volumes. Post-deployment fatigue resistance surpassed ISO requirements. The radial force of the helical deployment balloon at different filling pressures resulted in a fully developed anchorage profile of the valves from two thirds of their maximum deployment diameter onwards. By combining a unique balloon-expandable TAVR system that also caters for non-calcific AR with polymer leaflets, a powerful, potentially disruptive technology for heart valve disease has been incorporated into a TAVR that addresses global needs. While fulfilling key prerequisites for expanding the scope of TAVR to the vast number of patients of low- to middle income countries living with rheumatic heart disease the system may eventually also bring hope to patients of high-income countries presently excluded from TAVR for being too young., Competing Interests: “Strait Access Technologies” (SAT) is a start-up company of the University of Cape Town. HA, DB, JSc, HC, DW, and PZ own shares in SAT. JV, RC, and RS are employed by SAT. KP, BB, and MC are former employees and shareholders of SAT. BJ is a former employee of SAT. CS is employed by Auto Tissue Berlin. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Appa, Park, Bezuidenhout, van Breda, de Jongh, de Villiers, Chacko, Scherman, Ofoegbu, Swanevelder, Cousins, Human, Smith, Vogt, Podesser, Schmitz, Conradi, Treede, Schröfel, Fischlein, Grabenwöger, Luo, Coombes, Matskeplishvili, Williams and Zilla.)

Background: Response to neoadjuvant chemotherapy is associated with improved outcomes for patients with triple negative breast cancer (TNBC). Patients with residual disease are at increased risk of relapse and death from breast cancer. In this retrospective study, we aimed to evaluate the efficacy and safety of cisplatin added to standard neoadjuvant chemotherapy for locally advanced TNBC., Materials and Methods: All TNBC treated with neoadjuvant cisplatin 60mg/m2 once in 3 weeks with weekly paclitaxel for 12 weeks, following 8 weeks of dose-dense epirubicin 90mg/m2 or doxorubicin 60mg/m2 with cyclophosphamide 600mg/m2 were analyzed retrospectively. The data related to pathological complete response, adherence to planned therapy, disease-free survival and overall survival were collected., Results: Eighty-three patients were included, of whom 80% had stage III disease. Pathological complete response in both breast (T0/Tis) and axilla (N0) was observed in 48.1% of patients. Miller Payne grade 5 pathological response in the breast was seen in 61% of patients. Good partial responses (Miller Payne grades 3,4) were observed in 32.5% of patients. The remaining 6.5% were poor responders. Seventy-seven patients underwent surgery. The disease-free survival at 1 and 3 years for those who had a pathological complete response was 96.7% and 77.6%, respectively, and 92.3% and 62.7% for those who did not, respectively. The predominant adverse events were hematological, with anemia being the most common one., Conclusion: The addition of cisplatin to neoadjuvant chemotherapy with anthracycline and taxane in TNBC was tolerable and produced a high rate of pathological complete response. Cisplatin added to standard chemotherapy in patients with locally advanced TNBC could improve clinical outcomes.

We report a neural network model for predicting the electromagnetic response of mesoscale metamaterials as well as generate design parameters for a desired spectral behavior. Our approach entails treating spectral data as time-varying sequences and the inverse problem as a single-input multiple output model, thereby compelling the network architecture to learn the geometry of the metamaterial designs from the spectral data in lieu of abstract features., (© 2021. The Author(s).)

Mandibular osteomyelitis in paediatric population presents as painful swelling with progressive trismus. Often the aetiology for this form of progressive osteomyelitis is inconclusive. The infective aetiology in this condition is difficult to assign as bone tissue culture is found to be seldom positive. We present a case of an 11-year-old girl, with hearing and speech impairment, who presented with report of painful right-sided mandibular swelling with progressive trismus. Clinical, radiographic and histopathological findings were suggestive of sclerotic osteomyelitis. Bone tissue culture grew Methicillin-resistant Staphylococcus aureus , indicating a rare infective variant. Unlike the common belief, where osteomyelitic mandible needs a combination of medical and surgical management, our case was managed conservatively with only antibiotic therapy. Our patient responded well to the treatment with reduction in pain and gradual improvement in the mouth opening. Radiographically the mandibular involvement also showed complete regression., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Patients with coronavirus disease 2019 (COVID-19) can develop rapidly progressive respiratory failure. Ventilation strategies during the COVID-19 pandemic seek to minimize patient mortality. In this study we examine associations between the availability of emergency department (ED)-initiated high-flow nasal cannula (HFNC) for patients presenting with COVID-19 respiratory distress and outcomes, including rates of endotracheal intubation (ETT), mortality, and hospital length of stay., Methods: We performed a retrospective, non-concurrent cohort study of patients with COVID-19 respiratory distress presenting to the ED who required HFNC or ETT in the ED or within 24 hours following ED departure. Comparisons were made between patients presenting before and after the introduction of an ED-HFNC protocol., Results: Use of HFNC was associated with a reduced rate of ETT in the ED (46.4% vs 26.3%, P <0.001) and decreased the cumulative proportion of patients who required ETT within 24 hours of ED departure (85.7% vs 32.6%, P <0.001) or during their entire hospitalization (89.3% vs 48.4%, P <0.001). Using HFNC was also associated with a trend toward increased survival to hospital discharge; however, this was not statistically significant (50.0% vs 68.4%, P = 0.115). There was no impact on intensive care unit or hospital length of stay. Demographics, comorbidities, and illness severity were similar in both cohorts., Conclusions: The institution of an ED-HFNC protocol for patients with COVID-19 respiratory distress was associated with reductions in the rate of ETT. Early initiation of HFNC is a promising strategy for avoiding ETT and improving outcomes in patients with COVID-19.

Rates of PTSD remain elevated among U.S. Veterans, highlighting a need for innovative management tools. Previous studies have shown mobile apps to have positive effects on PTSD symptoms, but few apps have been examined systematically. This pilot study evaluated the perceived effectiveness and usability of Mindset, a novel mobile app that monitors user stress level via heart rate to encourage e-therapy use. The study sample included 30 community-residing Veterans who completed baseline assessments. They used the Mindset app and associated smartwatch until their approximate 1-month follow-up. Self-reported assessments included pre- and post-deployment experiences; experience with Mindset; and standard screeners for PTSD (PCL-M), anxiety (GAD-7), depression (PHQ-9), and alcohol use problems (AUDIT). Among the 24 participants who completed follow-up interviews, a significant decrease ( p  < 0.05) was found in PCL-M, PHQ-9, and modified AUDIT scores. Respondents reported moderate to high acceptance and satisfaction with Mindset features, though considerable frustration with the associated smartwatch. These findings highlight mHealth apps such as Mindset as potentially useful tools for PTSD and depression symptom management. These findings are also encouraging in the context of the current COVID-19 pandemic, which may accelerate further innovation and implementation of mHealth technologies to improve mental health self-care.