Evaluating the impact of a year-long external mentorship pilot program in classical hematology.

Effective mentorship is a pivotal factor in shaping the career trajectory of trainees interested in classical hematology (CH), which is of critical importance due to the anticipated decline in the CH workforce. However, there is a lack of mentorship opportunities within CH compared with medical oncology. To address this need, a year-long external mentorship program was implemented through the American Society of Hematology (ASH) Medical Educators Institute (MEI). Thirty-five hematology/oncology (H/O) fellows interested in CH and 34 academically productive faculty mentors from different institutions across North America were paired in a meticulous process that considered individual interests, experiences, and background. Pairs were expected to meet virtually once a month. Participation in a scholarly project was optional. A mixed-methods sequential explanatory design was used to evaluate the program using mentee and mentor surveys, a mentee interview, and a mentee focus group. Thirty-three (94.2%) mentee-mentor pairs completed the program. Sixty-three percent of mentee respondents worked on a scholarly project with their mentor; several mentees earned publications, grants, and awards. Mentee perception that their assigned mentor was a good match was associated with a perceived positive impact on confidence (p=0.0423), career development (p=0.0423), and professional identity (p=0.0302). Furthermore, twenty-three (66%) mentees accepted CH faculty positions after fellowship. All mentor respondents believed that this program would increase retention in CH. This mentorship program demonstrates a productive, beneficial way of connecting mentees and mentors from different institutions to improve the careers of CH trainees, with the ultimate goal of increasing retention in CH.

Machine learning characterization of a rare neurologic disease via electronic health records: a proof-of-principle study on stiff person syndrome.

BACKGROUND: Despite the frequent diagnostic delays of rare neurologic diseases (RND), it remains difficult to study RNDs and their comorbidities due to their rarity and hence the statistical underpowering. Affecting one to two in a million annually, stiff person syndrome (SPS) is an RND characterized by painful muscle spasms and rigidity. Leveraging underutilized electronic health records (EHR), this study showcased a machine-learning-based framework to identify clinical features that optimally characterize the diagnosis of SPS. METHODS: A machine-learning-based feature selection approach was employed on 319 items from the past medical histories of 48 individuals (23 with a diagnosis of SPS and 25 controls) with elevated serum autoantibodies against glutamic-acid-decarboxylase-65 (anti-GAD65) in Dartmouth Health's EHR to determine features with the highest discriminatory power. Each iteration of the algorithm implemented a Support Vector Machine (SVM) model, generating importance scores-SHapley Additive exPlanation (SHAP) values-for each feature and removing one with the least salient. Evaluation metrics were calculated through repeated stratified cross-validation. RESULTS: Depression, hypothyroidism, GERD, and joint pain were the most characteristic features of SPS. Utilizing these features, the SVM model attained precision of 0.817 (95% CI 0.795-0.840), sensitivity of 0.766 (95% CI 0.743-0.790), F-score of 0.761 (95% CI 0.744-0.778), AUC of 0.808 (95% CI 0.791-0.825), and accuracy of 0.775 (95% CI 0.759-0.790). CONCLUSIONS: This framework discerned features that, with further research, may help fully characterize the pathologic mechanism of SPS: depression, hypothyroidism, and GERD may respectively represent comorbidities through common inflammatory, genetic, and dysautonomic links. This methodology could address diagnostic challenges in neurology by uncovering latent associations and generating hypotheses for RNDs.

Repeated exposure to multiple concurrent stressors alters visual processing in the adult posterior parietal cortex.

Chronic stress is well known to erode cognitive functions. Yet, our understanding of how repeated stress exposure impacts one of the fundamental bases of cognition: sensory processing, remains limited. The posterior parietal cortex (PPC) is a high order visual region, known for its role in visually guided decision making, multimodal integration, attention, and working memory. Here, we used functional measures to determine how repeated exposure to multiple concurrent stressors (RMS) affects sensory processing in the PPC in adult male mice. A longitudinal experimental design, repeatedly surveying the same population of neurons using in vivo two-photon imaging, revealed that RMS disrupts the balanced turnover of visually responsive cells in layer 2/3 of the PPC. Across the population, RMS-induced changes in visual responsiveness followed a bimodal distribution suggesting idiosyncratic stress effects. In cells that maintained their responsiveness across recording sessions, we found that stress reduced visual response magnitudes and feature selectivity. While we did not observe stress-induced elimination of excitatory synapses, noise correlation statistics indicated that RMS altered visual input to the neuronal population. The impact of RMS was restricted to visually evoked responses and was not evident in neuronal activity associated with locomotion onset. Together, our results indicate that despite no apparent synaptic reorganization, stress exposure in adulthood can disrupt sensory processing in the PPC, with the effects showing remarkable individual variation.

PUM1-TRAF3 fusion protein activates non-canonical NF-κB signaling via rescued NIK in biliary tract cancer.

Discovery and verification of diagnostic or therapeutic biomarkers for biliary tract cancer (BTC) is challenging owing to the low prevalence of the disease. Here, we identified and investigated the clinical impact of a fusion gene, Pumilio1-tumor necrosis factor receptor-associated factor 3 (PUM1-TRAF3), caused by 1;14 chromosomal translocation in BTC. PUM1-TRAF3 was initially identified in the RNA-sequencing of five BTC surgical tissues and confirmed by fluorescence in situ hybridization. Expression of the fusion gene was validated in an expanded cohort (5/55, 9.1%). Establishment and molecular assessment of PUM1-TRAF3 expressing BTC cells revealed that PUM1-TRAF3 activates non-canonical NF-κB signaling via NF-κB-inducing kinase (NIK). Abnormal TRAF3 activity, driven by competitive binding of PUM1-TRAF3 and TRAF3 to NIK, led to NIK rescue followed by P52/RelB nuclear translocation, all of which were reverted by an NIK inhibitor. The elevated expression of NIK and activated NF-κB signaling was observed in the PUM1-TRAF3-expressing regions of patient tissues. Expression of the PUM1-TRAF3 fusion was significantly correlated with strong NIK expression, which is associated with a poorer prognosis for patients with BTC. Overall, our study identifies a new fusion gene, PUM1-TRAF3, that activates NIK and non-canonical NF-κB signaling, which may be beneficial for developing precise treatment strategies for BTC.

Stroke Measures Analysis of pRognostic Testing - Mortality (SMART-M) nomogram predicts long-term mortality after ischaemic stroke.

BACKGROUND: Predicting long-term mortality is essential for understanding prognosis and guiding treatment decisions in patients with ischemic stroke. Therefore, this study aimed to develop and validate the method for predicting 1-year and 5-year mortality after ischemic stroke. METHODS: We utilized data from the linked dataset comprising the administrative claims database of the Health Insurance Review and Assessment Service and the Clinical Research Center for Stroke registry data for patients with acute stroke within 7 days of onset. The outcome was all-cause mortality following ischemic stroke. Clinical variables linked to long-term mortality following ischemic stroke were determined. A nomogram was constructed based on the Cox's regression analysis. The performance of the risk prediction model was evaluated using the Harrell's C index. RESULTS: This study included 42,207 ischemic stroke patients, with a mean age of 66.6 years and 59.2% being male. The patients were randomly divided into training (n=29,916) and validation (n=12,291) groups. Variables correlated with long-term mortality in patients with ischemic stroke, including age, sex, body mass index, stroke severity, stroke mechanisms, onset-to-door time, pre-stroke dependency, history of stroke, diabetes mellitus, hypertension, coronary artery disease, chronic kidney disease, cancer, smoking, fasting glucose level, previous statin therapy, thrombolytic therapy such as intravenous thrombolysis and endovascular recanalization therapy, medications, and discharge modified Rankiin Scale were identified as predictors. We developed a predictive system named Stroke Measures Analysis of pRognostic Testing - Mortality (SMART-M) by constructing a nomogram using the identified features. The C-statistics of the nomogram in the developing and validation groups were 0.806 (95% confidence interval [CI], 0.802-0.812) and 0.803 (95% CI, 0.795-0.811), respectively. CONCLUSIONS: The SMART-M method demonstrated good performance in predicting long-term mortality in ischemic stroke patients. This method may help physicians and family members understand the long-term outcomes and guide the appropriate decision-making process.

Anatomical perspectives of brow-lifting using threads: Clinical cases with techniques.

INTRODUCTION: Tailoring surgical interventions to target age-related transformations is paramount. Many candidates seeking blepharoplasty commonly exhibit eyebrow ptosis, underscoring the necessity for surgeons to possess a comprehensive understanding of techniques for brow and forehead rejuvenation. METHODS: Various surgical techniques are available for eyebrow and forehead enhancement, contrasting the standardized approaches in upper and lower blepharoplasty. Thread lifting has gained popularity for forehead lifting, although a more precise term would be eyebrow lifting. The thread lifting methods using V and I techniques with floating-type threads (Secret Line, Hyundai Meditech., Inc., Wonju-si, Republic of Korea) are used. RESULTS: The natural aging process often causes the forehead and eyebrows to sag under the influence of gravity, leading to the appearance of heavy eyelids. Elevating the eyebrows can mitigate droopiness, enhance vision clarity, and rejuvenate the facial aesthetic. While non-surgical methods like Botulinum Toxin A can weaken muscles and potentially aid in brow elevation, their visible effects may be somewhat constrained. DISCUSSION: Surgical methods encompass endoscopic forehead lift, eyebrow lift techniques, and scalp excision-based forehead reduction surgery, each with specific advantages and drawbacks. Thread lifting bridges the gap between surgical and non-surgical modalities. Forehead areas often lack subcutaneous fat, requiring precise anatomical understanding for effective thread lifting. Cannula usage with partial tunneling ensures efficacy even in patients with strong adhesions. Presented cases showcase successful eyebrow lifting using cog threads, illustrating immediate and gradual post-procedure changes. CONCLUSION: Eyebrow thread lifting demands periodic procedures, offering subtler improvements than surgery. Anatomical knowledge is crucial, and the technique presents discomfort. Effects last about 6 months, requiring re-treatment as effects regress. Thread lifting, a middle ground between surgical and non-surgical methods, can rejuvenate brows with less downtime.

Prevalence and risk factors for gallstone and renal stone formation in patients with intestinal Behçet's disease.

Background/Aims: The association between inflammatory bowel disease (IBD) and gallstone and renal stone formation has been established. However, few studies have investigated this association in patients with intestinal Behçet's disease (BD). We aimed to examine the prevalence of gallstones and renal stones in patients with intestinal BD and identify potential risk factors. Methods: We analyzed gallstone and renal stone occurrences in 553 patients diagnosed with intestinal BD who had undergone cross-sectional imaging examinations between March 2005 and April 2021 at the IBD Center, Severance Hospital, Seoul, South Korea. Logistic regression models were used to identify risk factors for gallstone and renal stone formation. Results: Of 553 patients over a mean 12.1-year duration, 141 (25.4%) patients had gallstones and 35 (6.3%) had renal stones. In multivariate logistic regression analysis, disease duration > 19 years (OR 2.91, 95% CI 1.56-5.44, 0.002). No significant correlation 0.001), prior intestinal BD-related surgery (OR 2.29, 95% CI 1.42-3.68, p < 0.001), and disease activity index for intestinal BD scores ≥ 75 (OR 2.23, 95% CI 1.12-4.45, p = 0.022) were associated with increased gallstone occurrence. A positive correlation was observed between renal stones, disease duration > 19 years (OR 5.61, 95% CI 1.98-15.90, p = 0.001) and frequent hospitalization (> 3 times) (OR 3.29, 95% CI 1.52-7.13, p = 0.002). No significant correlation was observed between gallstone and renal stone occurrence. Conclusions: These findings contribute to greater understanding concerning gallstone and renal stone prevalence and associated risk factors in patients with intestinal BD.

Reverse and antegrade vector thread lifting techniques: Correcting nasolabial and marionette lines.

BACKGROUND: This study evaluates the efficacy of reverse and antegrade thread lifting vectors in conjunction with thread selection for correcting nasolabial folds and marionette lines, aiming to enhance treatment precision and effectiveness. METHODS: Three female patients aged 43, 48, and 53, presenting with primary concerns regarding nasolabial folds, underwent distinct treatment regimens utilizing various types of threads and vectors. Additionally, video demonstrations were recorded to showcase the procedural techniques employed in each case. RESULTS: The outcomes of the thread lifting procedures demonstrated significant improvements in the correction of the nasolabial fold and marionette line. CONCLUSION: Innovative thread insertion techniques involve entry points above the zygomatic arch and threading toward the temple hairline for lateral face lifting. These utilize barbs to pull skin and underlying tissues. The reversal technique involves inserting threads in a criss-cross pattern, forming a fibrous structure that may prolong the duration of results. Various thread combinations, considering factors such as composition, thickness, and barb size, provide customized procedures. This research introduces clinical applications, including temple area hairline lifting for nasolabial fold and marionette line correction, reverse vectors targeting nasolabial folds and marionette lines, and antegrade approaches from the lateral side.

Carbon materials and their metal composites for biomedical applications: A short review.

Carbon materials and their hybrid metal composites have garnered significant attention in biomedical applications due to their exceptional biocompatibility. This biocompatibility arises from their inherent chemical stability and low toxicity within biological systems. This review offers a comprehensive overview of carbon nanomaterials and their metal composites, emphasizing their biocompatibility-focused applications, including drug delivery, bioimaging, biosensing, and tissue engineering. The paper outlines advancements in surface modifications, coatings, and functionalization techniques designed to enhance the biocompatibility of carbon materials, ensuring minimal adverse effects in biological systems. A comprehensive investigation into hybrid composites integrating carbon nanomaterials is conducted, categorizing them as fullerenes, carbon quantum dots, carbon nanotubes, carbon nanofibers, graphene, and diamond-like carbon. The concluding section addresses regulatory considerations and challenges associated with integrating carbon materials into medical devices. This review culminates by providing insights into current achievements, challenges, and future directions, underscoring the pivotal role of carbon nanomaterials and their metal composites in advancing biocompatible applications.

Evaluation of Chronic Pancreatitis Prognosis Score in an American Cohort.

INTRODUCTION: Chronic Pancreatitis Prognosis Score (COPPS) was developed to discriminate disease severity and predict risk for future hospitalizations. In this cohort study, we evaluated if COPPS predicts the likelihood of hospitalization(s) in an American cohort. METHODS: The CPDPC consortium provided data and serum from subjects with chronic pancreatitis (N=279). COPPS was calculated with baseline data and stratified by severity (low, moderate, high). Primary endpoints included number and duration of hospitalizations during 12-month follow-up. RESULTS: The mean±SD COPPS was 8.4±1.6. COPPS correlated with all primary outcomes: hospitalizations for any reason (number: r=0.15, p=0.01; duration: r=0.16, p=0.01) and pancreas-related hospitalizations (number: r=0.15, p=0.02; duration: r=0.13, p=0.04). The severity distribution was 13.3% low, 66.0% moderate, and 20.8% high. 37.6% of subjects had ≥1 hospitalization(s) for any reason; 32.2% had ≥1 pancreas-related hospitalization(s). All primary outcomes were significantly different between severity groups: hospitalizations for any reason (number, p=0.004; duration, p=0.007) and pancreas-related hospitalizations (number, p=0.02; duration, p=0.04). The prevalence of continued drinking at follow-up (p=0.04) was higher in the low and moderate groups. The prevalence of anxiety at enrollment (p=0.02) and follow-up (p<0.05) was higher in the moderate and high groups. DISCUSSION: Statistically, COPPS significantly correlated with hospitalization outcomes, but the correlations were weaker than in previous studies, which may be related to the outpatient nature of the PROCEED cohort and lower prevalence of high severity disease. Studies in other prospective cohorts are needed to understand the full utility of COPPS as a potential tool for clinical risk assessment and intervention.

Comprehensive EHMT1 variants analysis broadens genotype-phenotype associations and molecular mechanisms in Kleefstra syndrome.

The shift to a genotype-first approach in genetic diagnostics has revolutionized our understanding of neurodevelopmental disorders, expanding both their molecular and phenotypic spectra. Kleefstra syndrome (KLEFS1) is caused by EHMT1 haploinsufficiency and exhibits broad clinical manifestations. EHMT1 encodes euchromatic histone methyltransferase-1-a pivotal component of the epigenetic machinery. We have recruited 209 individuals with a rare EHMT1 variant and performed comprehensive molecular in silico and in vitro testing alongside DNA methylation (DNAm) signature analysis for the identified variants. We (re)classified the variants as likely pathogenic/pathogenic (molecularly confirming Kleefstra syndrome) in 191 individuals. We provide an updated and broader clinical and molecular spectrum of Kleefstra syndrome, including individuals with normal intelligence and familial occurrence. Analysis of the EHMT1 variants reveals a broad range of molecular effects and their associated phenotypes, including distinct genotype-phenotype associations. Notably, we showed that disruption of the "reader" function of the ankyrin repeat domain by a protein altering variant (PAV) results in a KLEFS1-specific DNAm signature and milder phenotype, while disruption of only "writer" methyltransferase activity of the SET domain does not result in KLEFS1 DNAm signature or typical KLEFS1 phenotype. Similarly, N-terminal truncating variants result in a mild phenotype without the DNAm signature. We demonstrate how comprehensive variant analysis can provide insights into pathogenesis of the disorder and DNAm signature. In summary, this study presents a comprehensive overview of KLEFS1 and EHMT1, revealing its broader spectrum and deepening our understanding of its molecular mechanisms, thereby informing accurate variant interpretation, counseling, and clinical management.

Development of a deep-learning phenotyping tool for analyzing image-based strawberry phenotypes.

Introduction: In strawberry farming, phenotypic traits (such as crown diameter, petiole length, plant height, flower, leaf, and fruit size) measurement is essential as it serves as a decision-making tool for plant monitoring and management. To date, strawberry plant phenotyping has relied on traditional approaches. In this study, an image-based Strawberry Phenotyping Tool (SPT) was developed using two deep-learning (DL) architectures, namely "YOLOv4" and "U-net" integrated into a single system. We aimed to create the most suitable DL-based tool with enhanced robustness to facilitate digital strawberry plant phenotyping directly at the natural scene or indirectly using captured and stored images. Methods: Our SPT was developed primarily through two steps (subsequently called versions) using image data with different backgrounds captured with simple smartphone cameras. The two versions (V1 and V2) were developed using the same DL networks but differed by the amount of image data and annotation method used during their development. For V1, 7,116 images were annotated using the single-target non-labeling method, whereas for V2, 7,850 images were annotated using the multitarget labeling method. Results: The results of the held-out dataset revealed that the developed SPT facilitates strawberry phenotype measurements. By increasing the dataset size combined with multitarget labeling annotation, the detection accuracy of our system changed from 60.24% in V1 to 82.28% in V2. During the validation process, the system was evaluated using 70 images per phenotype and their corresponding actual values. The correlation coefficients and detection frequencies were higher for V2 than for V1, confirming the superiority of V2. Furthermore, an image-based regression model was developed to predict the fresh weight of strawberries based on the fruit size (R2 = 0.92). Discussion: The results demonstrate the efficiency of our system in recognizing the aforementioned six strawberry phenotypic traits regardless of the complex scenario of the environment of the strawberry plant. This tool could help farmers and researchers make accurate and efficient decisions related to strawberry plant management, possibly causing increased productivity and yield potential.

Comparison of EPIC Versus HIPEC in the Treatment of Colorectal Peritoneal Metastases and Appendix Tumors Using Inverse Probability of Treatment Weighting.

BACKGROUND: The selection of hyperthermic intraperitoneal chemotherapy (HIPEC) or early postoperative intraperitoneal chemotherapy (EPIC) for peritoneal metastases from colorectal cancer or appendiceal neoplasms following cytoreductive surgery (CRS) depends on the surgeon's discretion. This study was designed to compare postoperative and oncologic outcomes of HIPEC and EPIC using inverse probability of treatment weighting (IPTW). METHODS: This study included 175 patients who received HIPEC or EPIC following CRS at a single tertiary university hospital between December 1999 and December 2020. Inverse probability of treatment weighting analysis was performed to control for pretreatment characteristics between the two groups. Multivariate analysis was performed to determine factors associated with postoperative and survival outcomes. RESULTS: After IPTW, no significant differences in baseline demographics and tumor characteristics were observed between the two groups. The HIPEC group had a significantly longer operation time than the EPIC group. The EPIC group showed a significantly higher postoperative mortality rate than the HIPEC group. Operation time (odds ratio [OR] 1.01; 95% confidence interval [CI] 1.01-1.02; p < 0.001), bowel anastomosis (OR 7.25; 95% CI 1.16-45.2; p = 0.034), neoadjuvant chemotherapy (OR 7.62; 95% CI 1.85-31.4; p = 0.005), and EPIC (OR 8.76; 95% CI 2.16-35.5; p = 0.002) were independent risk factors for major surgical complications. No association was observed between intraperitoneal chemotherapy type and major hematologic toxicity, overall survival, progression-free survival, or peritoneal progression-free survival. CONCLUSIONS: EPIC was a risk factor for major surgical complications. Survival outcomes were similar between the two types of intraperitoneal chemotherapy.

Novel single-entry point injection technique for masseter hypertrophy treatment using botulinum neurotoxin based on patient-reported comfort.

INTRODUCTION: Botulinum neurotoxin (BoNT) injections are widely used for the treatment of masseter muscle hypertrophy in Southeast Asia. However, there remains a lack of consensus regarding the optimal injection technique. This study aimed to compare the efficacy and patient discomfort associated with single-entry point injections versus multiple three-point injections for masseter muscle hypertrophy treatment with BoNT. MATERIALS AND METHODS: Sixteen participants, comprising both male and female Korean adults aged 22-63, were enrolled in the study. On the left side of the face, single-entry point injections were administered, followed by multidirectional injections, while on the right side, three-point injections were given. Pain intensity during the procedure was assessed using visual analogue scale scores. RESULT: Our results revealed that participants experienced lower levels of pain with single-entry point injections compared to three-point injections (average visual analogue scores of 3.31 and 5.19, respectively). CONCLUSION: These findings highlight the potential benefits of single-entry point injections in reducing patient discomfort during masseter muscle hypertrophy treatment with BoNT. We advocate for further research to validate these findings and encourage practitioners to consider single-entry point injections as a viable option for enhancing treatment outcomes in their clinical practice.

Effect of a Combination of Lactiplantibacillus plantarum KC3 and Leonurus japonicus Extracts in Respiratory Discomfort: A Randomized, Double-Blind, Placebo-Controlled Trial.

The increased global prevalence of chronic respiratory diseases in recent years has caused a substantial public health burden. Lactiplantibacillus plantarum KC3 and Leonurus japonicus Houtt. (LJH) extracts can alleviate respiratory symptoms and improve lung function in vitro and in vivo. However, the clinical efficacy and safety profile of this combination in patients with respiratory diseases remain unclear. Therefore, this multicenter, randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the efficacy and safety of L. plantarum KC3 and LJH extracts in adults with respiratory discomfort. This mixture was termed 'CKDB-315'. Participants, randomly assigned to the CKDB-315 or placebo groups, were treated for 12 weeks. Assessments included the St. George's Respiratory Questionnaire (SGRQ) and the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). The CKDB-315 group showed considerably improved SGRQ and CAT scores compared with the placebo group. Secondary outcomes, including dyspnea, pulmonary function, total antioxidant status, and inflammatory cytokine levels, were consistent with the primary outcomes. Exploratory analyses of the gut microbiota and short-chain fatty acid contents revealed the potential mechanisms underlying the effects of CKDB-315. Finally, safety analysis indicated that CKDB-315 was well tolerated and caused few adverse events. Our findings indicate that CKDB-315 is a promising therapeutic option for respiratory discomfort in adults.

Volumizing Threads (Jamber) in the Midface and Managing Side Effects: Clinical Cases.

The clinical application of polydioxanone (PDO) threads, traditionally utilized for tissue lifting, is now being explored for its volumizing effects in midface rejuvenation. The novel approach involves employing PDO volumizing threads to achieve physical augmentation akin to a "solid filler." The study introduces a more convenient insertion method for these threads, prioritizing ease and efficacy. Clinical cases demonstrate the efficacy of volumizing threads in addressing midface concerns, such as nasolabial folds and midcheek grooves. Additionally, the integration of volumizing threads to provide support in sagging areas is examined for achieving natural-looking enhancements. While highlighting positive outcomes, potential side effects like thread protrusion are addressed, along with strategies for their mitigation. Volumizing threads are presented as a suitable procedure for patients wary of traditional fillers or seeking subtle enhancements, with the recommendation of combining them with cog threads for those desiring more pronounced changes in facial contour. In summary, volumizing thread offers a minimally invasive alternative with fewer side effects for midface rejuvenation.

Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes.

Trithorax-related H3K4 methyltransferases, KMT2C and KMT2D, are critical epigenetic modifiers. Haploinsufficiency of KMT2C was only recently recognized as a cause of neurodevelopmental disorder (NDD), so the clinical and molecular spectrums of the KMT2C-related NDD (now designated as Kleefstra syndrome 2) are largely unknown. We ascertained 98 individuals with rare KMT2C variants, including 75 with protein-truncating variants (PTVs). Notably, ∼15% of KMT2C PTVs were inherited. Although the most highly expressed KMT2C transcript consists of only the last four exons, pathogenic PTVs were found in almost all the exons of this large gene. KMT2C variant interpretation can be challenging due to segmental duplications and clonal hematopoesis-induced artifacts. Using samples from 27 affected individuals, divided into discovery and validation cohorts, we generated a moderate strength disorder-specific KMT2C DNA methylation (DNAm) signature and demonstrate its utility in classifying non-truncating variants. Based on 81 individuals with pathogenic/likely pathogenic variants, we demonstrate that the KMT2C-related NDD is characterized by developmental delay, intellectual disability, behavioral and psychiatric problems, hypotonia, seizures, short stature, and other comorbidities. The facial module of PhenoScore, applied to photographs of 34 affected individuals, reveals that the KMT2C-related facial gestalt is significantly different from the general NDD population. Finally, using PhenoScore and DNAm signatures, we demonstrate that the KMT2C-related NDD is clinically and epigenetically distinct from Kleefstra and Kabuki syndromes. Overall, we define the clinical features, molecular spectrum, and DNAm signature of the KMT2C-related NDD and demonstrate they are distinct from Kleefstra and Kabuki syndromes highlighting the need to rename this condition.

Comparison of Outcomes in Bowel Resections by Gynecologic Oncologists Versus General Surgeons During Maximal Cytoreductive Surgery for Advanced Ovarian Cancer: Gynecologic Oncology Research Investigators Collaboration Study (GORILLA-3006).

BACKGROUND: This report describes the oncologic outcomes for patients with advanced ovarian cancer who had bowel surgery performed by gynecologic oncologists (GOs) and compares the outcomes with those for bowel surgery performed by general surgeons (GSs) during maximal cytoreductive surgery. METHODS: Patients from six academic institutions who had FIGO stage III or IV ovarian cancer and underwent any bowel surgeries during maximal cytoreductive surgery were eligible for the study. The patients were divided into two groups according to whether bowel surgery was performed by a GO or a GS. In both groups, the GOs were mainly involved in extra bowel debulking procedures. Perioperative and survival outcomes were compared between the two groups. RESULTS: The 761 patients in this study included 113 patients who underwent bowel surgery by a GO and 648 who had bowel surgery by a GS. No discernible differences were observed in age, American Society of Anesthesiology (ASA) score, FIGO stage, histologic type, timing of cytoreductive surgery (primary or interval debulking surgery), or complications between the two groups. The GO group exhibited a shorter operation time than the GS group. Kaplan-Meier analysis showed no survival differences between the two groups. In the Cox analysis, non-serous cell types and gross residual diseases were associated with adverse effects on overall survival. However, performance of bowel surgery by a GO did not have an impact on survival. CONCLUSION: Performance of bowel surgery by a GO during maximal cytoreductive surgery is both feasible and safe. These results should be reflected in the training system for GOs regarding bowel surgery, and further research is needed to confirm that GOs can play a more leading role in performing extra-uterine procedures.