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Src homology 2 (SH2) domains play a critical role in cellular signal transduction. They bind to peptides containing phosphotyrosine (pY) with various specificities that depend on the flanking amino-acid residues. The SH2 domain of growth-factor receptor-bound protein 2 (Grb2) specifically recognizes pY-X-N-X, whereas the SH2 domains in phosphatidylinositol 3-kinase (PI3K) recognize pY-X-X-M. Binding of the pY site in CD28 (pY-M-N-M) by PI3K and Grb2 through their SH2 domains is a key step that triggers the CD28 signal transduction for T cell activation and differentiation. In this study, we determined the crystal structure of the Grb2 SH2 domain in complex with a pY-containing peptide derived from CD28 at 1.35 Å resolution. The peptide was found to adopt a twisted U-type conformation, similar to, but distinct from type-I β-turn. In all previously reported crystal structures, the peptide bound to the Grb2 SH2 domains adopts a type-I β-turn conformation, except those with a proline residue at the pY+3 position. Molecular modeling also suggests that the same peptide bound to PI3K might adopt a very different conformation.

Background: With estimated global postoperative mortality rates at 1% to 4% leading to approximately 3 million to 12 million deaths per year, an urgent need exists for reliable measures of perioperative risk. Existing approaches suffer from poor performance, place a high burden on clinicians to gather data, or do not incorporate intraoperative data. Previous work demonstrated that intraoperative anesthetics induce prefrontal electroencephalogram (EEG) oscillations in the alpha band (8 to 12 Hz) that correlate with postoperative cognitive outcomes., Methods: The authors analyzed a retrospective cohort of 1,081 patients undergoing surgery with general anesthesia at Massachusetts General Hospital (Boston, Massachusetts) with intraoperative EEG recordings. The association between EEG alpha power and adverse outcomes was characterized using statistical models that were fitted on propensity weighted data. The primary outcome was postoperative mortality, measured from date of surgery to date of death or last follow-up. Secondary outcomes included mortality within prespecified time windows (30 days, 90 days, 180 days, and 1 yr), hospital and postanesthesia care unit lengths of stay, discharge to long-term care, and 30-day hospital readmission., Results: Alpha power was associated with mortality risk (hazard ratio, 0.92; 95% CI, 0.85 to 0.99; P = 0.039). Within specified time windows, alpha power was associated with 30-day mortality (odds ratio, 0.81; 95% CI, 0.66 to 0.95; P = 0.010), 90-day mortality (odds ratio, 0.68; 95% CI, 0.55 to 0.79; P < 0.001), 180-day mortality (odds ratio, 0.75; 95% CI, 0.66 to 0.83; P < 0.001), and 1-yr mortality (odds ratio, 0.85; 95% CI, 0.79 to 0.91; P < 0.001). Additionally, alpha power was associated with discharge to long-term care (odds ratio, 0.91; 95% CI, 0.86 to 0.96; P < 0.001). We did not find significant associations among alpha power and 30-day readmission and hospital or postanesthesia care unit lengths of stay., Conclusions: Intraoperative EEG alpha power is independently associated with postoperative mortality and adverse outcomes, suggesting it could represent a broad measure of postoperative physical resilience and provide clinicians with a low-burden, personalized measure of postoperative risk., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc., on behalf of the American Society of Anesthesiologists.)

Background: Anastomotic leak after colorectal resection is associated with morbidity, mortality, and poor bowel function. Minimal data exist on the relationship between anastomotic technique, intraoperative leak test, and subsequent clinical leak, particularly on the utility of performing end-to-end anastomosis (EEA) vs non-EEA (NEEA) to avoid postoperative leaks. This study aimed to analyze potential associations between anastomotic construction, intraoperative anastomotic assessments, and clinical leak., Methods: This was a retrospective cohort study comparing anastomotic techniques used in patients with colorectal cancer who underwent left-sided colorectal resections with colorectal or coloanal anastomoses at a tertiary care center. The outcomes were rates of intraoperative air leak, incomplete anastomotic donuts, and postoperative clinical leak. Univariate and multivariate analyses were performed to evaluate the potential association between anastomotic technique and intraoperative anastomotic assessments and subsequent leak., Results: Among 844 patients, 27 (3.2%) had intraoperative leak, 6 (0.7%) had incomplete donuts, and 27 (3.2%) experienced clinical leak. Of note, 500 patients (59.2%) had EEAs, and 344 patients (40.7%) had NEEAs. There were no significant differences in demographics or comorbidities between groups (P >.05) or rates of incomplete donuts (P =.07). EEA was associated with significantly more intraoperative air leaks than NEEA on univariate analysis (4.9% vs 1.2%, respectively; P =.005) and multivariate analysis (odds ratio [OR], 3.6; 95% CI, 1.01-12.50; P =.049). There was no difference in postoperative clinical leak between the groups on univariate analysis (3.0% in EEA vs 3.5% in NEEA; P =.69) or multivariate analysis (OR, 0.97; 95% CI, 0.40-2.34; P =.94)., Conclusion: EEA is associated with higher rates of intraoperative air leak than NEEA, even after adjusting for potential confounders., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Objective: Electroconvulsive therapy (ECT) is utilized for treating psychiatric disorders, such as schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD). We aimed to compare pre- and post-ECT treatment outcomes between patients with SCZ and a combined group of patients with MDD and BD (MDD+BD) to assess the distinction between the antipsychotic and antidepressant effects of ECT., Methods: ECT was administered to patients with SCZ (n = 17) and those with MDD+BD (n = 7). Symptoms were evaluated using the brief psychiatric rating scale (BPRS), clinical global impression scale (CGI), and global assessment of functioning (GAF). Plasma brain-derived neurotrophic factor (BDNF) levels were also measured., Results: The BPRS, CGI, and GAF scores significantly differed after ECT compared with those before ECT in each patient group. However, no significant differences were observed between the groups for each disorder. No significant differences were observed in plasma BDNF levels between the groups at baseline and during ECT. At baseline, only depression scores were more favorable in the SCZ group, whereas positive symptoms and disorganization scores were higher in the MDD+BD group. During treatment, positive symptoms, activation, and disorganization items were significantly more favorable in the MDD+BD group compared with the SCZ group. Total BPRS scores were not associated with plasma BDNF levels; however, rating scores of the several items related to activation, resistance, and disorganization were positively correlated with BDNF levels., Conclusion: ECT effects on several clinical outcomes in the MDD+BD group were associated with plasma BDNF levels. These findings suggest that ECT may be more effective for treating MDD than SCZ.

Introduction: Little is known about the association between age and fecal ostomy surgery trends over time. We aim to 1) determine the rate of fecal ostomy operations over time and 2) compare rates of colostomy formation between patients older and younger than 65 y., Materials and Methods: Retrospective multi-institutional cohort study of patients ≥18 y who underwent colorectal resection between 2003 and 2014 using the Nationwide Inpatient Sample database. Patients were identified using International Classification of Diseases, 9th edition Procedural Codes. A difference-in-difference analysis was performed to evaluate the differences in colostomy formation between age groups., Results: Out of 819,441 adult patients who underwent major colorectal resection, 136,840 (16.6%) required ostomy formation. Median age was 63 y (interquartile range 51-74), 50% were female. Overall, 82,606 (10.0%) patients underwent a colostomy formation and 54,234 (6.6%) an ileostomy formation. Rates of colostomy formation decreased (13.2%-7.1% in <65 and 14.0%-7.2% in ≥65). Incidence of ileostomy formation increased for both age groups (6.1%-9.9% in <65 and 3.8%-6.3% in ≥65). The difference-in-difference analysis showed that the decline in colostomy formation was less pronounced among the older adult cohort (odds ratio 0.49, 95% confidence interval 0.47-0.50) than those <65 (odds ratio 0.42, 95% confidence interval 0.41-0.44)., Conclusions: Incidence of colostomy formation decreased in both groups over the study period. In contrast, the decline in colostomy formation was slower among older adults. This highlights a significant change in surgical trends across the United States with increasing rates of ileostomy use. Appropriate resource allocation and support are vital to the recovery of this growing surgical patient population., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Chemoradiation-induced lymphopenia is common and associated with poorer survival in multiple solid malignancies. However, the association between chemoradiation-related lymphopenia and survival outcomes in rectal cancer is yet unclear. The objective of this study was to evaluate the prognostic impact of lymphopenia and its predictors in patients with rectal cancer undergoing neoadjuvant chemoradiation., Methods: The inclusion criteria for this single-institution retrospective study were as follows: (1) biopsy-proven diagnosis of rectal adenocarcinoma, (2) receipt of neoadjuvant chemoradiation followed by surgery, and (3) absolute lymphocyte count available prior to and within 12 weeks of chemoradiation. In general, chemoradiation consisted of 5-fluorouracil or capecitabine and radiotherapy with 50.4 Gy over 28 fractions. Lymphopenia was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The primary variable of interest was absolute lymphocyte count nadir within 12 weeks of chemoradiation, dichotomized by <500/μL (grade 3 or worse lymphopenia). The primary endpoint was overall survival. Cox modeling and Kaplan-Meier methods were used to perform survival analyses., Results: A total of 193 patients were identified with a median follow-up of 68 months. Overall clinical stage was 2 in 21% and 3 in 76%. Median baseline lymphocyte count for the entire cohort was 1700/μL. One hundred ten patients (57%) experienced chemoradiation-related severe lymphopenia. Pathologic complete response rate was 21%; 83% received adjuvant chemotherapy. Lower baseline lymphocyte count was significantly associated with increased risk for chemoradiation-related severe lymphopenia (odds ratio, 1.71). On multivariable Cox regression analysis, chemoradiation-related severe lymphopenia was significantly associated with worse disease-free survival (hazard ratio, 2.64) and overall survival (hazard ratio, 4.32). Five-year overall survival was 79% versus 92%, and 5-year disease-free survival was 70% versus 86% in the cohort that experienced versus did not experience severe lymphopenia, respectively., Discussion: Chemoradiation-induced lymphopenia is common and a prognostic marker of poorer survival in rectal cancer. Closer observation in high-risk patients and treatment modifications may be potential approaches to mitigating treatment-related lymphopenia. Our findings also suggest an important role of the host immunity in rectal cancer outcomes and support future studies investigating ways to reduce treatment-induced lymphopenia., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Interval to surgery following short course radiotherapy (SCRT) for rectal cancer is not standardized. This study investigated pathologic outcomes and survival with varying intervals to surgery., Methods: Using the National Cancer Database, adults who received SCRT from 2005 to 2020 were grouped by additional neoadjuvant chemotherapy. Outcomes were analyzed for early (within 1 week) and delayed (over 4 weeks) intervals., Results: Of 1154 patients, 671 received neoadjuvant SCRT and chemotherapy (Group 1: median interval 29 days, 50% delayed) and 483 received SCRT only (Group 2: median interval 9 days, 27% delayed). In Group 1, delay was associated with tumor downstaging (OR 1.61; 95% CI, 1.03-2.51; p = 0.036), decreased lymphovascular invasion (OR 0.53; 95% CI, 0.33-0.85; p = 0.009), and complete pathologic response (OR 2.86; 95% CI, 1.06-7.76; p = 0.039). Delay was associated with decreased tumor deposits in Group 1 (OR 0.46; 95% CI, 0.30-0.71; p < 0.001) and Group 2 (OR 0.37; 95% CI 0.21-0.65; p = 0.001). Survival was not affected., Conclusion: Delaying surgery following neoadjuvant SCRT results in favorable pathologic outcomes without impacting overall survival, regardless of neoadjuvant chemotherapy., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Lymphadenectomy during right hemicolectomy for colon cancer varies between the U.S. and Japan., Methods: Patients undergoing right hemicolectomy for non-metastatic right-sided colon cancer between 2010 and 2019 ​at U.S. and Japanese institutions were compared. Outcomes included survival, pathologic findings, and postoperative complications., Results: 319 American patients (57 ​% female, mean age 70 years) underwent conventional resection and 308 Japanese patients (52 ​% female, mean age 70 years) underwent extended dissection. The conventional group underwent more laparotomies (26.6 ​% vs. 8.4 ​%, p ​< ​0.001), had more poorly differentiated histology (31.7 ​% vs. 11.0 ​%, p ​< ​0.01), lower lymph node yield (M ​= ​27 ​± ​11 vs. M ​= ​32 ​± ​14, p ​< ​0.001), and more 30-day readmissions (31 vs. 5, p ​< ​0.001). Adjusting for demographics, pathology, perioperative outcomes, and adjuvant chemotherapy, extended lymphadenectomy improved disease-free survival (HR 0.50; 95 ​% CI, 0.31-0.80; p ​= ​0.004), but not overall survival (HR 0.98; 95 ​% CI, 0.95-1.02; p ​= ​0.14)., Conclusions: Extended lymphadenectomy for right sided-colon cancer improves disease-free, but not overall, survival among Japanese patients., Competing Interests: Declaration of competing interest The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors confirm that this manuscript has not been published elsewhere and is not under consideration by another journal., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Mobile health (mHealth) platforms are being used to understand patient-reported experiences before and after surgery. Currently, there is limited literature describing the feasibility of using mHealth to evaluate patient experience among older adults. The objective of this study was to determine the feasibility of using mHealth to evaluate patient-reported outcomes among patients older and younger than 65 years undergoing elective colectomy for diverticulitis., Methods: A prospective pilot study was performed between June 1, 2020 and August 31, 2021, enrolling patients aged > 18 years undergoing elective colectomy for diverticulitis at a single academic center (n = 62). A Health Insurance Portability and Accountability Act-compliant mHealth platform was used to deliver patient-reported quality-of-life surveys at 3 time points: preoperatively, 3 months postoperatively, and 6 months postoperatively. The primary outcome was the feasibility of using mHealth in patients older and younger than 65 years to collect outcomes using recruitment, engagement, and survey completion rates. Preliminary findings of patient experiences were evaluated for patients older and younger than 65 years as secondary outcomes., Results: Overall, 33.9% of participants were older than 65 years with a median age of 59.8 years (IQR, 53.3-67.9). mHealth enrollment was high (100%) with survey response rates of 79% preoperatively, 64.5% at 3 months postoperatively, and 17.7% at 6 months postoperatively. Response rates were similar among patients older and younger than 65 years (P = .79 preoperatively and P = .39 at 3 months postoperatively)., Conclusion: Utilization of mHealth to evaluate patient-reported outcomes is feasible in the preoperative and early postoperative settings, including older adults undergoing elective surgery for diverticulitis. Future work will focus on improving long-term outcomes to better examine potential differences when considering patient-centered outcomes among older adult patients., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Key Message: In Cyrtanthus mackenii, development of embryo and endosperm were differentially affected by fertilization of male gametes with DNA damage and mutations. Pollen irradiation with ionizing radiations has been applied in plant breeding and genetic research, and haploid plant induction has mainly been performed by male inactivation with high-dose irradiation. However, the fertilization process of irradiated male gametes and the early development of embryo and endosperm have not received much attention. Heavy-ion beams, a type of radiation, have been widely applied as effective mutagens for plants and show a high mutation rate even at low-dose irradiation. In this study, we analyzed the effects of male gametes of Cyrtanthus mackenii irradiated with a carbon-ion beam at low doses on fertilization. In immature seeds derived from the pollination of irradiated pollen grains, two types of embryo sacs were observed: embryo sac with a normally developed embryo and endosperm and embryo sac with an egg cell or an undivided zygote and an endosperm. Abnormalities in chromosome segregation, such as chromosomal bridges, were observed only in the endosperm nuclei, irrespective of the presence or absence of embryogenesis. Therefore, in Cyrtanthus, embryogenesis is strongly affected by DNA damage or mutations in male gametes. Moreover, various DNA contents were detected in the embryo and endosperm nuclei, and endoreduplication may have occurred in the endosperm nuclei. As carbon-ion irradiation causes chromosomal rearrangements even at low doses, pollen irradiation can be an interesting tool for studying double fertilization and mutation heritability., (© 2024. The Author(s).)

Objective: To create a recurrence prediction value (RPV) of high-risk factor and identify the patients with high risk of cancer recurrence., Background: There are several high-risk factors known to lead to poor outcomes. Weighting each high-risk factor based on their association with increased risk of cancer recurrence can provide a more precise understanding of risk of recurrence., Methods: We performed a multi-institutional international retrospective analysis of patients with stage II colon cancer patients who underwent surgery from 2010 to 2020. Patient data from a multi-institutional database were used as the Training data, and data from a completely separate international database from 2 countries were used as the Validation data. The primary endpoint was recurrence-free survival., Results: A total of 739 patients were included from Training data. To validate the feasibility of RPV, 467 patients were included from Validation data. Training data patients were divided into RPV low (n=564) and RPV high (n=175). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low [hazard ratio (HR) 2.628; 95% confidence interval (CI) 1.887-3.660; P <0.001). Validation data patients were divided into 2 groups (RPV low, n=420) and RPV high (n=47). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (HR 3.053; 95% CI 1.962-4.750; P <0.001)., Conclusions: RPV can identify stage II colon cancer patients with high risk of cancer recurrence worldwide., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The leaves and branches of rabbiteye blueberry are rich in proanthocyanidins, which are thought to have different physiological activities depending on their structure and degree of polymerization. In this study, we analyzed the constituents of the leaves and branches of rabbiteye blueberry to determine the seasonal variations in polyphenol and proanthocyanidin (PAC) contents as well as their mean degrees of polymerization (mDP). Total PAC content was determined using two methods: The p-dimethylaminocinnamaldehyde (DMACA) method, which measures monomeric PAC, showed an increase from spring to summer in both leaves and branches. On the other hand, using the butanol/HCl method, which measures only polymerized PAC, the PAC content of leaves increased from spring to summer but those of branches remained low throughout the year, showing no significant increase or decrease. Furthermore, analysis of the mDP of PAC showed increases from spring to summer in the leaves of 'Kunisato 35 gou'. Although the highest value (8.0) was observed in October, values around 4 remained throughout the year in the branches. Since differences in polymerization degree affect absorption in the body and physiological properties such as antioxidant capacity, selecting the appropriate harvest time and plant organs for each purpose is expected to ensure the quality of processed blueberry foods.