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OBJECTIVE: This study aimed to evaluate the efficacy and tolerability of perampanel, which was used in a cohort of patients with refractory epilepsy for up to 3.5 years in a real-world setting in Saudi Arabia. PATIENTS AND METHODS: Data from the medical records of patients treated with perampanel between March 13th, 2017, and September 6th, 2020, at neurology clinics at King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh and Jeddah, Saudi Arabia, was collected. The Liverpool Adverse Events Profile (LAEP) scale was also used to measure the adverse effects of perampanel. RESULTS: Of the 75 included patients, 66.7% responded to perampanel at the last follow-up, including 22.7% seizure-free for at least the last six months, and 44% of patients responded with a ≥ 50% reduction in seizure frequency from baseline. The overall incidence of adverse effects that led to perampanel discontinuation was 13.3%; the most common adverse effect was aggressive behavior followed by sedation. Pre-existing psychiatric comorbidity was significantly associated with the incidence of psychiatric and behavioral adverse effects on perampanel (p = 0.0206). The mean score of LEAP was 40. The most frequently rated adverse effects in LEAP were "feelings of anger and aggression to others", "nervousness and/or agitation" and "sleepiness". The efficacy and tolerability of perampanel were dose-dependent. Dose 6 mg/day was the most frequently used dose that was taken by about one-third of patients at their last visit. CONCLUSIONS: Perampanel was effective as an adjunctive treatment for intractable seizures, with a responder rate of 66.7%. The long-term tolerability of perampanel was generally good. Aggressive behavior was the most common reason for perampanel discontinuation. Patients should be counseled and monitored for these adverse effects, particularly those with a history of previous psychiatric and behavioral problems. [ABSTRACT FROM AUTHOR]

Fenomena di era pandemic ini proses pemelajaran dilakukan melalui daring. Kenyataannya tidak semua peserta didik tidak memiliki media untuk mengakses pembelajaran secara daring. Hal ini tentu berdampak terhadapa motivasi dan proses pembelajaran peserta didik. Penelitian ini dilakukan untuk menjawab rumusan masalah yaitu bagaimanakah Implementasi kompetensi Sosial guru dalam meningkatkan motivasi ekstrinsik siswa pada pembelajaran Pendidikan Agama Islam di SMAN 1 Telukjambe Kabupaten Karawang. Untuk mengumpulkan data penulis menggunakan metode wawancara, observasi dan dokumentasi. Setelah data terkumpul maka dianalisa dalam analisis deskriptif kualitatif.. Setelah penulis sajikan dan penulis analisa, maka dapat disimpulkan bahwa: Implementasi Kompetensi sosial guru dalam meningkatkan motivasi ekstrinsik siswa pada pembelajaran Pendidikan Agama Islam di SMAN 1 Telukajambe Kabupaten Karawang dikategorikan baik. Indikatornya adalah meningkatnya antusias siswa dalam mengikuti pembelajaran PAI meski pembelajaran di lakukan secara daring. Adapun faktor-faktor yang mempengaruhi kompetensi sosial guru PAI dalam meningkatkan motivasi ekstrinsik siswa ini adalah tingkat pendidikan guru, faktor sarana dan prasarana, dan terjalinnya komunikasi yang efektif.

Background: Limited data are available on the prevalence and prognostic significance of human papillomavirus (HPV) in squamous cell carcinoma of head and neck (SCCHN) in the Indian population.Aim: The present study aimed to determine the prevalence of HPV and p16 in an Indian cohort of SCCHN and assess their correlation and influence of tobacco use on patient outcomes.Materials and Methods: The p16 and HPV status of 170 patients of SCCHN treated with curative chemoradiotherapy was determined using immunohistochemistry and polymerase chain reaction, respectively, and further correlated with their demographic characteristics. In addition, genotyping of HPV-positive samples was performed. Survival outcomes were analyzed and compared for both p16 positive (p16 +ve) and p16 negative (p16 -ve) population. The influence of tobacco use on outcomes was assessed.Results: p16 expression was observed in 20% (34/170) cases whereas HPV positivity was detected in 39.4% (67/170) of SCCHN patients with HPV16 being the most common (91%) subtype. About 73.5% patients were p16 +ve among the tobacco users in this cohort (83.5%). Interestingly, p16 positivity was significantly associated with nonusers of tobacco (P = 0.02) and younger females (P = 0.06). The p16 +ve and p16 -ve groups did not exhibit a significant difference in the 5-year cause-specific survival (CSS) (79% vs. 72.2%), disease-free survival (DFS) (78.3% vs. 68.3%, P = 0.5), and locoregional control (LRC) (82.2% vs. 71.5%, P = 0.4). However, the outcome analyses in tobacco nonusers revealed a definite large improvement in CSS (P = 0.08) and a trend toward improvement in DFS (P = 0.15) and LRC (P = 0.11) in the p16 +ve versus the p16 -ve groups.Conclusion: The low prevalence of p16 positivity (20%) and dual HPV and p16 positivity (38.8%) in the studied Indian cohort indicates the low utility of p16 as a surrogate for HPV in the background of high tobacco burden. The outcomes are largely improved in a small subset of SCCHN cases comprising p16 +ve tobacco nonusers. [ABSTRACT FROM AUTHOR]

This study aims to improve student learning outcomes of PAI through the Group Investigation learning model. This research is a classroom action research conducted at SDN 003 Tasik Juang. The subjects of this study were 30 people. The research will be carried out from August to September 2019. The research instrument used was an observation sheet and a test of learning outcomes. The results showed an increase in student learning activities and outcomes with a percentage of student activities in the first cycle of 57.5% with enough categories increased to 72.5% with a high category, student learning outcomes in the first cycle showed as many as 17 students or 56.7% who meet the KKM value set with an average learning outcome of 64.5 which is included in the category of being increased in the second cycle which shows as many as 24 students or 80% have met the KKM with an average of 75.3 which is included in the high category. Based on these results it can be concluded that the learning model of Group Investigation can improve the learning outcomes of PAI SDN 003 Tasik Juang students.

Abstract Background Oral cancer is a common cancer and a major health problem in the Indian subcontinent. At our laboratory Mcl-1, an anti-apoptotic member of the Bcl-2 family has been demonstrated to be overexpressed in oral cancers and to predict outcome in oral cancer patients treated with definitive radiotherapy. To study the role of Mcl-1 isoforms in radiation response of oral squamous carcinoma cells (OSCC), we investigated in the present study, the association of Mcl-1 isoform expression with radiosensitivity of OSCC, using siRNA strategy. Methods The time course expression of Mcl-1 splice variants (Mcl-1L, Mcl-1S & Mcl-1ES) was studied by RT-PCR, western blotting & immunofluorescence, post-irradiation in oral cell lines [immortalized FBM (radiosensitive) and tongue cancer AW8507 & AW13516 (radioresistant)]of relatively differing radiosensitivities. The effect of Mcl-1L knockdown alone or in combination with ionizing radiation (IR) on cell proliferation, apoptosis & clonogenic survival, was investigated in AW8507 & AW13516 cells. Further the expression of Mcl-1L protein was assessed in radioresistant sublines generated by fractionated ionizing radiation (FIR). Results Three to six fold higher expression of anti-apoptotic Mcl-1L versus pro-apoptotic Mcl-1S was observed at mRNA & protein levels in all cell lines, post-irradiation. Sustained high levels of Mcl-1L, downregulation of pro-apoptotic Bax & Bak and a significant (P P P Conclusion Our studies suggest that Mcl-1L isoform has an important role in the survival and radioresistance of OSCC and may be a promising therapeutic target in oral cancers.

Aim: The risk of lymph node metastasis after endoscopic resection of high-risk T1 colorectal cancer prompts additional resection. However, age and comorbidities are considered in decision-making and some surgeons opt for observation. We compared the long-term outcomes of these approaches with the aim of clarifying the need for additional resection., Method: This multicentre retrospective study included high-risk T1 colorectal cancer patients treated with endoscopic submucosal dissection (ESD) between January 2013 and April 2021. Patients who met one or more of the following criteria were eligible for inclusion: submucosal invasion depth ≥1000 μm, vessel invasion, poor differentiation, budding grade 2/3 or a positive vertical margin. Patients were divided into resection (R) and observation (O) groups. Outcomes were evaluated based on overall survival (OS) and 5-year cancer-specific survival (CSS), with an additional stratified analysis using the age-adjusted Charlson comorbidity index (ACCI)., Results: The study included 178 patients (group R, n = 131; group O, n = 47). Patients in group O were significantly older and had more comorbidities. Group R showed better 5-year OS and CSS (OS 87.0% vs. 58.9%, p = 0.001; CSS 98.8% vs. 78.4%, p = 0.002). Stratification by ACCI revealed that benefits of additional resection remained for patients with ACCI ≤ 6 (OS 91.2% vs. 58.3%, p = 0.013; CSS 98.4% vs. 61.7%, p < 0.001) but not for those with ACCI ≥7 (OS 75.9% vs. 59.8%, p = 0.289; CSS 100% vs. 100%, p = 0.617)., Conclusions: Significant survival benefits were demonstrated in group R patients with high-risk T1 cancer. However, the survival benefit of additional surgical resection was unconfirmed in patients with ACCI ≥ 7., (© 2025 Association of Coloproctology of Great Britain and Ireland.)

Purpose: There have been no adequate comparisons of the efficacy, safety, and efficiency of analgesia after laparoscopic colorectal resection (LAC), with and without epidural anesthesia (EDA)., Methods: This was a multicenter prospective observational study of patients undergoing LAC. The primary end point was the mean visual analog scale (VAS) score on postoperative days (PODs) 1-7. The secondary end points were the highest VAS, complication rate, days to first ambulation and fatigue, length of hospital stay, and time to commencement of surgery., Results: We compared an EDA group (Group E, n = 48) and a no-EDA group (Group O, n = 48) after matching. The mean VAS was not significantly different between the groups (28.7 vs. 30.1, p = 0.288). On assessing the secondary end points, the highest VAS was not significantly different between the groups. In fact, the VAS was lower in Group E only on POD 2. There was no difference in the incidence of complications, the time to first postoperative evacuation was shorter in Group E, and postoperative hospitalization was similar. The time to surgery was shorter in Group O., Conclusion: These results suggest that LAC without EDA is a feasible option, but with the early and regular use of adjunctive measures to provide more stable analgesia., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Objectives: To investigate and compare the effects of three different high-definition (HD) non-invasive current stimulation (NICS) protocols on the spinal cord on support balance and somatosensory abilities in healthy young people., Methods: Fifty-eight students were enrolled in this crossover study. All participants underwent application of (i) 1.5 mA anodal high-definition trans spinal direct current stimulation (HD-tsDCS), (ii) 1.5 mA cathodal HD-tsDCS, (iii) 1.5 mA high-definition trans spinal alternating current stimulation (HD-tsACS), and (iv) sham HD-tsDCS/ACS over the eighth thoracic vertebra in a randomised order. Balance (Y Balance test), deep sensitivity (Tuning Fork Test), and superficial sensitivity (Monofilament Test) of the lower limbs were tested immediately before and after each intervention., Results: Balance ability improved significantly following anodal HD-tsDCS and HD-tsACS compared with that following sham HD-tsDCS/ACS. Similarly, deep sensitivity increased significantly with anodal HD-tsDCS and HD-tsACS compared to that with sham HD-tsDCS/ACS and cathodal HD-tsDCS. Furthermore, superficial sensitivity improved significantly following anodal HD-tsDCS compared with that after HD-tsACS and cathodal HD-tsDCS., Conclusions: Our data show that HD-tsNICS effectively modulates the balance and somatosensory control of the lower limbs. Several diseases are associated with illness-induced changes in the spinal network in parallel with sensorimotor disabilities. Non-invasive spinal modulation may be a favourable alternative to conventional brain applications in rehabilitation. Future studies should therefore investigate these promising approaches among cohorts of patients with disabilities.

Antimicrobial resistance has emerged as a significant danger to global health, and the need for more effective antimicrobial resistance (AMR) control has been highlighted. Cinnamic acid is abundant in plant products and is a potential starting material for further modification, focusing on the development of new antimicrobial compounds. In the following review, we describe the classification of critical antibacterial-guided reactions applied to the main skeleton structure of cinnamic acid derivatives over the last decade. Of all of the main parts of cinnamic acids, the phenyl ring and the carboxylic group significantly affect antibacterial activity. The results presented in the following review can provide valuable insights into considerable features in the organic modification of cinnamic acids related to antibacterial medication development and the food industry.

Introduction: Indocyanine green fluorescence imaging (ICG-FI) reduces anastomotic leakage (AL) in rectal cancer surgery. However, no studies investigating risk factors for anastomotic leakage specific to the group using ICG-FI have ever previously been conducted. The purpose of this retrospective multicenter study was to ascertain the risk factors for AL in the group using ICG-FI., Methods: A total of 638 patients who underwent laparoscopic or robotic anterior resection for rectal cancer between April 2018 and March 2023 were included in this study. Patients were divided into two groups: the ICG-FI group (n = 269) and the non-ICG-FI group (n = 369) for comparative analysis. The effects of clinicopathological and treatment-related factors on AL in the ICG-FI group were evaluated using both univariate and multivariate analyses., Results: The incidence of AL in the ICG-FI group was 4.8%. Although there was no significant difference in the incidence of AL between the two groups, it was observed to be lower in the ICG-FI group. A multivariate analysis revealed a preoperative C-reactive protein-to-albumin ratio (CAR) ≥ 0.049 (odds ratio, 3.73; 95% confidence interval, 1.01-13.70; p = 0.048) as an independent risk factor for AL in the ICG-FI group., Conclusions: In this study, CAR was the only identified risk factor for AL in the ICG-FI group. It was suggested that CAR could be a criterion for early surgical intervention, prior to the escalation of risks, or for considering interventions such as diverting stoma creation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Exposure to ionizing radiation has been linked to cardiovascular diseases. However, the impact of moderate doses of radiation on abdominal aortic aneurysm (AAA) remains unknown., Methods: Angiotensin II-infused Apoe-/- mice were irradiated (acute, 1 Gray) either 3 days before (Day-3) or 1 day after (Day+1) pomp implantation. Isolated primary aortic vascular smooth muscle cells (VSMCs) were irradiated (acute 1 Gray) for mechanistic studies and functional testing in vitro., Results: Day-3 and Day+1 irradiation resulted in a significant reduction in aorta dilation (Control: 1.39+/-0.12; Day-3: 1.12+/-0.11; Day+1: 1.15+/-0.08 mm, P<0.001) and AAA incidence (Control: 81.0%; Day-3: 33.3%, Day+1: 53.3%) compared to the non-irradiated group. Day-3 and Day+1 irradiation led to an increase in collagen content in the adventitia (Thickness control: 23.64+/-2.9; Day-3: 54.39+/-15.5; Day+1 37.55+/-10.8 mm, P = 0.006). However, the underlying protective mechanisms were different between Day-3 and Day+1 groups. Irradiation before Angiotensin II (AngII) infusion mainly modulated vascular smooth muscle cell (VSMC) phenotype with a decrease in contractile profile and enhanced proliferative and migratory activity. Irradiation after AngII infusion led to an increase in macrophage content with a local anti-inflammatory phenotype characterized by the upregulation of M2-like gene and IL-10 expression., Conclusion: Moderate doses of ionizing radiation mitigate AAA either through VSCM phenotype or inflammation modulation, depending on the time of irradiation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Riazi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim: Intracorporeal anastomosis (IA) is becoming increasingly popular and replacing extracorporeal anastomosis (EA) for reconstruction in laparoscopic and robotic surgery for right-sided colon cancer (LSRCC). Intracorporeal overlap anastomosis (IOA) is the most widely used IA technique. This study aimed to examine the safety of IOA by investigating its short-term results during the implementation phase., Methods: This multicenter prospective cohort study was conducted by the Kanagawa Yokohama Colorectal Cancer (KYCC) Study Group. Patients with stage 1-3 colon cancer who planned to undergo LSRCC with IOA reconstruction were eligible. The incidence of anastomotic leakage (AL) of Clavien-Dindo (C-D) grade ≥3 was evaluated as the primary endpoint, and other surgical outcomes and postoperative complications of C-D grades ≥2 were the secondary endpoints., Results: A total of 127 patients were enrolled, of whom 120 were finally analyzed. The incidence of C-D grade ≥2 complications was 8.3%. The incidence of C-D grade ≥3 AL was 0.8%. This trend was lower than that reported in previous randomized controlled trials (RCTs) and acceptable. Additionally, 1.7% of the patients developed abdominal abscesses, and no cases of anastomotic stenosis were observed. The median operative time was 257 min, and the reconstruction procedure required 32 min. Stapler closure of the enterotomy and facility experience of more than 30 cases were associated with a shorter reconstruction time during IOA., Conclusion: IOA is feasible and can be safely performed during the implementation phase in patients undergoing LSRCC., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Objectives: Existing applications of non-invasive brain stimulation in the modulation of balance ability are focused on the primary motor cortex (M1). It is conceivable that other brain and spinal cord areas may be comparable or more promising targets in this regard. This study compares transcranial direct current stimulation (tDCS) over (i) the M1, (ii) the cerebellum, and (iii) trans-spinal direct current stimulation (tsDCS) in the modulation of balance ability., Methods: Forty-two sports students were randomized in this placebo-controlled study. Twenty minutes of anodal 1.5 mA t/tsDCS over (i) the M1, (ii) the cerebellum, and (iii) the spinal cord, as well as (iv) sham tDCS were applied to each subject. The Y Balance Test, Single Leg Landing Test, and Single Leg Squat Test were performed prior to and after each intervention., Results: The Y Balance Test showed significant improvement after real stimulation of each region compared to sham stimulation. While tsDCS supported the balance ability of both legs, M1 and cerebellar tDCS supported right leg stand only. No significant differences were found in the Single Leg Landing Test and the Single Leg Squat Test., Conclusions: Our data encourage the application of DCS over the cerebellum and spinal cord (in addition to the M1 region) in supporting balance control. Future research should investigate and compare the effects of different stimulation protocols (anodal or cathodal direct current stimulation (DCS), alternating current stimulation (ACS), high-definition DCS/ACS, closed-loop ACS) over these regions in healthy people and examine the potential of these approaches in the neurorehabilitation.

Objective: This study aimed to evaluate the efficacy and tolerability of perampanel, which was used in a cohort of patients with refractory epilepsy for up to 3.5 years in a real-world setting in Saudi Arabia., Patients and Methods: Data from the medical records of patients treated with perampanel between March 13th, 2017, and September 6th, 2020, at neurology clinics at King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh and Jeddah, Saudi Arabia, was collected. The Liverpool Adverse Events Profile (LAEP) scale was also used to measure the adverse effects of perampanel., Results: Of the 75 included patients, 66.7% responded to perampanel at the last follow-up, including 22.7% seizure-free for at least the last six months, and 44% of patients responded with a ≥ 50% reduction in seizure frequency from baseline. The overall incidence of adverse effects that led to perampanel discontinuation was 13.3%; the most common adverse effect was aggressive behavior followed by sedation. Pre-existing psychiatric comorbidity was significantly associated with the incidence of psychiatric and behavioral adverse effects on perampanel (p = 0.0206). The mean score of LEAP was 40. The most frequently rated adverse effects in LEAP were "feelings of anger and aggression to others", "nervousness and/or agitation" and "sleepiness". The efficacy and tolerability of perampanel were dose-dependent. Dose 6 mg/day was the most frequently used dose that was taken by about one-third of patients at their last visit., Conclusions: Perampanel was effective as an adjunctive treatment for intractable seizures, with a responder rate of 66.7%. The long-term tolerability of perampanel was generally good. Aggressive behavior was the most common reason for perampanel discontinuation. Patients should be counseled and monitored for these adverse effects, particularly those with a history of previous psychiatric and behavioral problems.

Despite fertility patients' reports of significant distress, few have access to integrated mental health care services. We elucidate the benefits and challenges of mental health integration in infertility practices from the perspective of both patients and providers. We outline specific models of integration, financial viability, and the first steps fertility clinics could take to improve their patients' access to these critical supports., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

We aimed to review the global literature in the past 10 years regarding the impact of infertility on depression, anxiety, stress, and quality of life while exploring the potential clinical utility of psychosocial fertility questionnaires. PubMed, Scopus, and CINAHL were searched for English-published articles since 2013 on key search terms related to infertility, assisted reproductive technologies, and psychological terms such as depression, anxiety, mood disorders, and quality of life. The search yielded 7,947 articles, of which 366 articles were independently deemed relevant by the 3 reviewers. Anxiety, depression, and diminished quality of life are prevalent in the infertility experience of both men and women. Studies from around the world show similar experiences independent of culture., Competing Interests: Declaration of interests A.M.B. has nothing to disclose. T.D. has nothing to disclose. I.K.L. has nothing to disclose. A.B. has nothing to disclose. S.W. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Clostridioides difficile (C difficile) is one of the most common health care-associated infections that negatively impact patient care and health care costs. This study takes a unique approach to C difficile infection (CDI) control by investigating key prevention obstacles through the perspectives of Stanford health care (SHC) frontline health care personnel., Methods: An anonymous qualitative survey was distributed at SHC, focusing on knowledge and practice of CDI prevention guidelines, as well as education, communication, and perspectives regarding CDI at SHC., Results: 112 survey responses were analyzed. Our findings unveiled gaps in personnel's knowledge of C difficile diagnostic guidelines and revealed a need for targeted communication and guideline-focused education. Health care staff shared preferences and recommendations, with the majority recommending enhanced communication of guidelines and information as a strategy for reducing CDI rates. The findings were then used to design and propose internal recommendations for SHC to mitigate the gaps found., Discussion: Many guidelines and improvement strategies are based on strong scientific and medical foundations; however, it is important to ask whether these guidelines are effectively translated into practice. Frontline health care workers hold empirical perspectives that could be key in infection control., Conclusions: Our findings emphasize the importance of including frontline health care personnel in infection prevention decision-making processes and the strategies presented here can be applied to mitigating infections in different health care settings., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: There are well-known methods for decompressing the colorectal tract before surgery, including transanal decompression tubes (TDT) and self-expanding metallic stents (SEMS). This study aimed to compare the short and long-term results in patients with malignant large bowel obstruction in whom TDT or SEMS were placed before surgery., Methods: This retrospective observational study enrolled 225 patients with malignant large bowel obstruction in whom TDT or SEMS were placed preoperatively and underwent R0 resection between 2008 and 2020. One-to-two propensity score matching was performed according to patient characteristics. Short- and long-term outcomes were compared. The primary endpoint was relapse-free survival (RFS). The secondary endpoints were the overall survival (OS) and postoperative complication rate., Results: Fifty-seven patients in the TDT group and 114 in the SEMS group were matched. The 3-year RFS rates were 66.7% in the TDT group and 69.9% in the SEMS group (p = 0.54), and the 3-year OS rates were 90.5% in the TDT group and 87.1% in the SEMS group (p = 0.52). No significant differences in the long-term results were observed between the two groups. Regarding short-term results, the SEMS group had significantly fewer stoma construction (p = 0.007) and shorter postoperative hospitalization (p < 0.001). The incidence of postoperative complications (grade ≥ 2) was significantly lower in the SEMS group (p = 0.04)., Conclusion: No significant differences in the long-term results were observed between the TDT and SEMS group. The SEMS showed significant usefulness in terms of improving short-term outcomes., (© 2023 Wiley Periodicals LLC.)

The increased stability of mutant p53 (Mutp53) plays a crucial role in its gain of function, making proteins involved in its stabilization promising targets for drug intervention. Although curcumin is known to exhibit anti-cancer effects, its role as a deubiquitinase (DUB) inhibitor in Mutp53 destabilization remains poorly explored. Our study demonstrates that curcumin treatment induced ubiquitination and destabilization of Mutp53 but not Wild-type p53 (WTp53) in cancer cells. Furthermore, proteasome and lysosome inhibitors failed to reverse the effect of curcumin, indicating Mutp53 destabilization is possibly via an alternate mechanism. Intriguingly, curcumin treatment also resulted in the nuclear aggregation of the Mutp53 protein, which was rescued by combined Dithiothreitol (DTT) treatment. Similar to curcumin, a broad-spectrum deubiquitinase inhibitor induced Mutp53 aggregation implying curcumin possibly acts by inhibiting deubiquitinases. Additionally, curcumin treatment inhibited colony-forming abilities, induced cytoplasmic vacuolation, and cell death selectively in Mutp53-expressing cells. Collectively, our study highlights the potential of curcumin as a promising therapeutic agent for targeting Mutp53-expressing cancer cells., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Oral cancer is a common malignant tumor of the oral cavity that affects many countries with a prevalent distribution in the Indian subcontinent, with poor prognosis rate on account of locoregional metastases. Gain-of-function mutations in p53 and overexpression of its related transcription factor, p63 are both widely reported events in oral cancers. However, targeting these alterations remains a far-achieved aim due to lack of knowledge on their downstream signaling pathways. In the present study, we characterize the isoforms of p63 and using knockdown strategy, decipher the functions and oncogenic signaling of p63 in oral cancers. Using Microarray and Chromatin Immunoprecipitation experiments, we decipher a novel transcriptional regulatory axis between p63 and Activin A and establish its functional significance in migration of oral cancer cells. Using an orally bioavailable inhibitor of the Activin A pathway to attenuate oral cancer cell migration and invasion, we further demonstrate the targetability of this signaling axis. Our study highlights the oncogenic role of ΔNp63 - Activin A - SMAD2/3 signaling and provides a basis for targeting this oncogenic pathway in oral cancers., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Translationally controlled tumour protein (TCTP) is a multifunctional protein elevated in multiple cancers. However, studies on its role in oral carcinogenesis and prognosis are rare. We recently reported the role of its interacting partner, MCL1, in oral cancer progression and outcome. Hence, the present study aimed to assess TCTP expression in oral tumorigenesis and its association with patient outcomes alone and in combination with MCL1., Methods: TCTP expression was assessed by immunohistochemistry and immunoblotting in oral tissues and cells, respectively. Cell viability post siRNA/dihydroartemisinin treatment was analysed by tetrazolium salt assay. Cell survival, invasion and tumorigenic potential post TCTP knockdown were assessed by clonogenic, Matrigel and soft-agar assays, respectively. The association of TCTP with patient outcome was analysed by Kaplan-Meier and Cox regression., Results: TCTP was significantly overexpressed in oral premalignant lesions (p < 0.0001), oral tumours (p < 0.0001) and oral dysplastic and cancer cells versus normal oral mucosa and also in recurrent (p < 0.05) versus non-recurrent oral tumours. Further, elevated TCTP was significantly (p < 0.05) associated with poor recurrence free survival (RFS) and poor overall survival (OS; hazard ratio = 2.29; p < 0.05). Intriguingly, the high co-expression of TCTP and MCL1 further reduced the RFS (p < 0.05) and OS (p < 0.05; hazard-ratio = 3.49; p < 0.05). Additionally, TCTP knockdown decreased survival (p < 0.05), invasion (p < 0.01) and in vitro tumorigenic potential (p < 0.0001). Dihydroartemisinin treatment reduced TCTP levels and viability of oral cancer cells., Conclusion: Our studies demonstrate an oncogenic role of TCTP in oral cancer progression and poor outcome. Thus, TCTP may be a potential prognostic marker and therapeutic target in oral cancers., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: This study compared the surgical outcomes between laparoscopic colectomy (LC) and open colectomy (OC) for mid-transverse colon cancer (MTC)., Methods: This multicenter retrospective study compared the short- and long-term surgical outcomes for patients with advanced MTC (T3 and T4 with or without nodal involvement) who underwent LC or OC between January 2008 and December 2019 using a propensity score-matched analysis., Results: A total of 177 patients with advanced MTC were enrolled. After matching, 58 cases for the OC and LC groups were selected. No significant differences in age, sex, tumor progression, or procedure type (extended resection or segmental resection) existed between groups. The LC group had significantly less blood loss (20 mL vs. 50 mL, p=0.048) and a shorter postoperative hospital stay (8 days vs. 12 days, p<0.001) than the OC group. Postoperative complications (Clavien-Dindo grade ≥ 2) occurred in 27.6% and 25.9% of the OC and LC groups respectively (p=1). Three patients (5.2%) and one patient (1.7%) of the OC and LC groups respectively developed anastomotic leakage (p=0.62). Re-operation was required in five patients (8.6%) in the OC group and one patient (1.7%) in the LC group (p=0.21). No surgery-related deaths occurred in either group. The 3-year overall survival rates (stage II: LC 100% vs. OC 92.8%, p=0.15; stage III: 88.9% vs. 84.3%, p=0.88, respectively) were similar between the two groups., Conclusion: LC is a minimally invasive technique with lesser blood loss, shorter postoperative hospital stays, and oncologic equivalence to OC. Hence, LC is useful for MTC treatment., Trial Registration: UMIN000042676., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Elevated expression of anti-apoptotic proteins, such as Bcl-2 and Mcl-1 contributes to poor prognosis and resistance to current treatment modalities in multiple cancers. Here, we report the design, synthesis and characterization of benzimidazole chalcone and flavonoid scaffold-derived bicyclic compounds targeting both Bcl-2 and Mcl-1 by optimizing the structural differences in the binding sites of both these proteins. Initial docking screen of Bcl-2 and Mcl-1 with pro-apoptotic protein Bim revealed possible hits with optimal binding energies. All the optimized bicyclic compounds were screened for their in vitro cytotoxic activity against two oral cancer cell lines (AW8507 and AW13516) which express high levels of Bcl-2 and Mcl-1. Compound 4d from the benzimidazole chalcone series and compound 6d from the flavonoid series exhibited significant cytotoxic activity (IC 50 7.12 μM and 17.18 μM, respectively) against AW13516 cell line. Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) analysis further demonstrated that compound 4d and compound 6d could effectively inhibit the Bcl-2 and Mcl-1 proteins by displacing their BH3 binding partners. Both compounds exhibited potent activation of canonical pathway of apoptosis evident from appearance of cleaved Caspase-3 and PARP. Further, treatment of oral cancer cells with the inhibitors induced dissociation of the BH3 only protein Bim from Mcl-1 and Bak from Bcl-2 but failed to release Bax from Bcl-xL thereby confirming the nature of compounds as BH3-mimetics selectively targeting Bcl-2 and Mcl-1. Our study thus identifies bicyclic compounds as promising candidates for anti-apoptotic Bcl-2/Mcl-1 dual inhibitors with a potential for further development., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Nutrient availability fluctuates in most natural populations, forcing organisms to undergo periods of fasting and re-feeding. It is unknown how dietary changes influence liver homeostasis. Here, we show that a switch from ad libitum feeding to intermittent fasting (IF) promotes rapid hepatocyte proliferation. Mechanistically, IF-induced hepatocyte proliferation is driven by the combined action of systemic FGF15 and localized WNT signaling. Hepatocyte proliferation during periods of fasting and re-feeding re-establishes a constant liver-to-body mass ratio, thus maintaining the hepatostat. This study provides the first example of dietary influence on adult hepatocyte proliferation and challenges the widely held view that liver tissue is mostly quiescent unless chemically or mechanically injured., Competing Interests: AS, YJ, BD, CL, YY, TA, PW, MM, NN, HN, ER, MF, AK, AM No competing interests declared, RN Reviewing editor, eLife, (© 2023, Sarkar et al.)

Cell proliferation is tightly controlled by inhibitors that block cell cycle progression until growth signals relieve this inhibition, allowing cells to divide. In several tissues, including the liver, cell proliferation is inhibited at mitosis by the transcriptional repressors E2F7 and E2F8, leading to formation of polyploid cells. Whether growth factors promote mitosis and cell cycle progression by relieving the E2F7/E2F8-mediated inhibition is unknown. We report here on a mechanism of cell division control in the postnatal liver, in which Wnt/β-catenin signaling maintains active hepatocyte cell division through Tbx3 , a Wnt target gene. The TBX3 protein directly represses transcription of E2f7 and E2f8 , thereby promoting mitosis. This cascade of sequential transcriptional repressors, initiated by Wnt signals, provides a paradigm for exploring how commonly active developmental signals impact cell cycle completion.

Introduction: Previous randomized controlled trials demonstrated similar oncological outcomes between laparoscopic-assisted (LA) and open (OP) colectomy; however, patients with transverse colon cancer were not analyzed. The aim of this study was to confirm the oncological safety and the advantages of the short- and long-term results of LA surgery for transverse colon cancer in comparison to OP surgery., Materials and Methods: The study data were retrospectively collected from the databases of four hospitals. Patients with transverse colon cancer who underwent LA or OP R0 or R1 resection were registered., Results: Among the 204 patients, 149 underwent OP colectomy and 55 underwent LA colectomy. The median follow-up period was 43 months. The rate of conversion to OP resection was 7.3%. The 5-year overall survival rate of the LA group was higher than that of the OP surgery group for all-stage patients (97.5% vs. 91.1%, P = 0.108), and it was similar in Stage II and Stage III patients (94.1% vs. 94.2%, P = 0.510). The LA group had significantly lower blood loss and a significantly longer operative time in comparison to the OP surgery group. Furthermore, the postoperative hospital stay was significantly shorter (9 vs. 13 days, P = 0.001) and the incidence of Grade ≥III complications was lower in the LA group (3.7% vs. 14.8%, P = 0.031)., Conclusion: We concluded that LA surgery for transverse colon cancer is oncologically safe and yields better short-term results in comparison to OP surgery., Competing Interests: None

Background/aim: Postoperative complications are associated with increased recurrence in colorectal cancer (CRC). We investigated the impact of infectious complications on the recurrence of CRC and overall survival after curative surgery in a single study group., Patients and Methods: In total, 1,668 patients who underwent radical resection for CRC in Yokohama City University, Yokohama Minami Kyosai Hospital, and Kanagawa Cancer Center between 2011 and 2019 were reviewed. Patients were classified into those with infectious complications (IC group) and those without infectious complications (Non-IC group). The risk factors for recurrence-free survival (RFS) and overall survival (OS) were analyzed., Results: Postoperative complications were found in 560 of the 1,668 patients (33.5%), and IC, which occurred in 312 patients (18.7%), included pneumonia, anastomotic leakage, and intraperitoneal abscess. The 5-year OS rates in the Non-IC and IC groups were 95.5% and 90.4%, respectively, while the 5-year RFS rates were 74.4% and 68.1%, respectively. The multivariate analysis demonstrated that postoperative IC were significant independent risk factors for OS and RFS., Conclusion: The presence of postoperative IC after CRC resection is associated with decreased long-term survival. The surgical procedure, surgical strategy, and perioperative care should be carefully planned in order to avoid causing IC., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The aim of this study was to explore the effects of chronic low-dose-rate gamma-radiation at a multi-scale level. The specific objective was to obtain an overall view of the endothelial cell response, by integrating previously published data on different cellular endpoints and highlighting possible different mechanisms underpinning radiation-induced senescence., Materials and Methods: Different datasets were collected regarding experiments on human umbilical vein endothelial cells (HUVECs) which were chronically exposed to low dose rates (0, 1.4, 2.1 and 4.1 mGy/h) of gamma-rays until cell replication was arrested. Such exposed cells were analyzed for different complementary endpoints at distinct time points (up to several weeks), investigating cellular functions such as proliferation, senescence and angiogenic properties, as well as using transcriptomics and proteomics profiling. A mathematical model was proposed to describe proliferation and senescence., Results: Simultaneous ceasing of cell proliferation and senescence onset as a function of time were well reproduced by the logistic growth curve, conveying shared equilibria between the two endpoints. The combination of all the different endpoints investigated highlighted a dose-dependence for prematurely induced senescence. However, the underpinning molecular mechanisms appeared to be dissimilar for the different dose rates, thus suggesting a more complex scenario., Conclusions: This study was conducted integrating different datasets, focusing on their temporal dynamics, and using a systems biology approach. Results of our analysis highlight that different dose rates have different effects in inducing premature senescence, and that the total cumulative absorbed dose also plays an important role in accelerating endothelial cell senescence., Competing Interests: The authors have declared that no competing interests exist.

Background and Objectives: Contrary to the Japanese guidelines recommendations regarding lateral lymph node dissection (LatLND) for rectal cancer, its omission is common in clinical practice without reliable omission criteria. Negative pathological mesorectal lymph node metastasis (MesLNM) is reportedly highly correlated with negative pathological lateral lymph node metastasis (p-LatLNM); however, this cannot be used as a criterion because pathological features are revealed postoperatively. Herein, we prospectively evaluated the negative predictive value (NPV) of MesLNM diagnosed via the one-step nucleic acid amplification (OSNA) method for p-LatLNM., Methods: This prospective study was conducted at a single academic study group in Japan. The key eligibility criterion was mid-to-low rectal cancer planned to be treated using mesorectal excision with LatLND. According to the study protocol, the OSNA method was considered useful if the point estimate of the NPV exceeded 95%., Results: Preoperative case registration was conducted between 2018 and 2020; 34 patients were registered. Among these, 16 were negative for OSNA-MesLNM, and negative p-LatLNM was confirmed in all cases. The point estimate of the NPV was 100%, with the 95% confidence interval ranging from 79.4% to 100.0%., Conclusions: The OSNA method is useful in selecting patients in whom LatLND can be omitted in real-world clinical practice., (© 2021 Wiley Periodicals LLC.)

Scopoletin is regarded as a major constituent of noni (Morinda citrifolia L), which contributes to the antioxidative, anti-inflammatory, immunomodulatory, and hepatoprotective properties in noni. It is also suggested as a marker for identification and quality control of noni and its derivative products. With the increasing interest in noni due to its health benefits and therapeutic effects, it is important to establish a reliable extraction and analysis method to determine scopoletin content in noni samples. The present study proposes the use of accelerated solvent extraction (ASE) to extract scopoletin from noni, followed by detection using HPLC-DAD for rapid identification and quantification of scopoletin. The optimum operating conditions of ASE were investigated using response surface methodology (RSM), using a three factors central composite design. It was found that the optimum scopoletin yield was achieved by performing the extraction at an elevated temperature of 60 °C for 12 min, using ethanol as extraction solvent with solid to solvent ratio of 1:30 (w/v). The analytical method validation was carried out under optimum conditions. The results indicate that the proposed ASE-HPLC-DAD method was adequately sensitive for the quantification of scopoletin in extracts with limit of detection of 0.17 μg/g. The presented method also exhibits excellent linearity from 0.54 to 120.10 μg/g with R 2 0.9995, high precision with RSD lower than 2% for intra-day and inter-day replication, and good recovery (99.88%). The established method was also successfully applied for scopoletin determination in noni product samples. The developed method provides a rapid and reliable method for the identification and quantification of scopoletin in noni samples that is suitable for routine procedures., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We describe our experience with robotic posterior rectopexy for a patient with full-thickness rectal prolapse. To our knowledge, this is the first report of such a case in the literature. A 94-year-old woman presented with a history of gradually worsening rectal prolapse. On examination, we found that the rectum was completely prolapsed, and we observed a prolapsed intestinal tract. Surgery was indicated and robotic rectopexy was performed without intraoperative complications. The postoperative course was uneventful, and she was discharged 10 days after the operation. One year later, there were no signs of recurrence. Robotic surgery has become common in recent years. We used robotic surgery for rectopexy, including the suturing procedure. Suturing in robotic surgery is easier than that in laparoscopic surgery, and we demonstrated that robotic rectopexy could be safely and easily performed. The trial was registered in the UMIN clinical trial registry (number 000040378)., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2022 by The Japan Society of Coloproctology.)

Polyploidy is a common and dynamic feature of mature rodent and human hepatocytes. While polyploidization occurs naturally during growth, alterations in the distribution of diploid and polyploid cells in the liver can be indicative of tissue stress or a pathologic state. Here, we describe a method for flow cytometric quantification of ploidy distribution by staining with propidium iodide. We first outline a hepatocyte isolation procedure from mouse liver through a two-step perfusion system for analysis of cellular ploidy. In an alternative approach, we employ a nuclei isolation protocol to assess nuclear ploidy. Finally, we describe how the use of fluorescent cell markers is compatible with these methods and helps retain information on cellular position within the tissue., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The antiapoptotic B cell lymphoma-2 (Bcl-2) family members are apical regulators of the intrinsic pathway of apoptosis that orchestrate mitochondrial outer membrane permeabilization (MOMP) through interactions with their proapoptotic counterparts. Overexpression of antiapoptotic Bcl-2 family proteins has been linked to therapy resistance and poor prognosis in diverse cancers. Among the antiapoptotic Bcl-2 family members, predominant overexpression of the prosurvival myeloid cell leukemia-1 (Mcl-1) has been reported in a myriad of hematological malignancies and solid tumors, contributing to therapy resistance and poor outcomes, thus making it a potential druggable target. The unique structure of Mcl-1 and its complex regulatory mechanism makes it an adaptive prosurvival switch that ensures tumor cell survival despite therapeutic intervention. This review focusses on diverse mechanisms adopted by tumor cells to maintain sustained elevated levels of Mcl-1 and how high Mcl-1 levels contribute to resistance in conventional as well as targeted therapies. Moreover, recent developments in the Mcl-1-targeted therapeutics and the underlying challenges and considerations in designing novel Mcl-1 inhibitors are also discussed., Competing Interests: The authors have no potential or existing conflicts of interest., (© The Author(s) 2022.)

Background: Resection of the primary lesion with radical lymph node dissection is the most promising treatment avenue for patients with cancer. On the other hand, these procedures often induce excessive intraoperative blood loss (IBL) and require perioperative blood transfusion. The influence of IBL on the long-term postoperative outcomes of patients with digestive cancer is controversial. We investigated the impact of IBL on survival and recurrence after curative surgery in patients with colorectal cancer (CRC) in a single study group., Patients and Methods: In total, 1,597 patients who underwent radical resection for CRC at three group hospitals between 2000 and 2019 were reviewed. Patients were classified into a group with high IBL (≥200 ml) or low IBL (<200 ml). The risk factors for disease-free (DFS) and overall (OS) survival were analyzed., Results: A total of 489 and 1,108 patients were classified into the high and low IBL groups, respectively. The OS and DFS rates at 5 years after surgery were 89.3% and 63.4%, respectively, for the high IBL group and 96.9% and 77.8% for the low IBL group; these differences were statistically significantly (p<0.001). The multivariate analysis demonstrated that IBL was a significant independent risk factor for OS and DFS., Conclusion: The amount of IBL was associated with significant differences in the OS and DFS of patients with stage II/III CRC who received curative resection. The surgical procedure, surgical strategy, and perioperative care should be carefully planned to avoid causing IBL., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: D3 lymph node dissection (LND) for stage II and III colon cancer has been shown to improve prognosis, however, it generally increases surgical stress. Studies have reported that the C-reactive protein/albumin ratio (CAR) may be a useful inflammatory-nutritional biomarker to predict postoperative complications and poor prognosis for with various types of cancer. Our purposes were to assess the short- and long-term outcomes of D3 LND in patients with a high preoperative CAR (≥ 0.04)., Patients and Methods: This was a retrospective cohort analysis reviewing a prospectively collected database of Yokohama City University and three affiliated hospitals. A total of 449 patients with stage II or III colon cancer with high CAR who underwent primary resection with D2 or D3 LND were identified between 2008 and 2020. The primary and secondary outcomes of interests were the 3-year recurrence-free survival and postoperative complication rates., Results: After propensity matching, 230 patients were evaluated. There was no significant difference between the D3 and D2 groups in the rate of postoperative complications overall (14.8% versus 11.3%, p=0.558), however, the incidence of anastomotic leakage tended to be greater in the D3 group (9.6% versus 2.6%, p=0.050). The long-term findings showed that there was no significant difference between the two groups (3-year recurrence-free survival rate: 77.2% versus 77.2%, p=0.880)., Conclusion: D3 LND did not improve survival outcomes for patients with colon cancer with a poor CAR in this study. D2 LND may be a treatment option for patients with stage II-III colon cancer with a high preoperative CAR., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Overexpression of anti-apoptotic MCL-1 protein in oral squamous cell carcinoma (OSCC) is linked to disease progression, therapy resistance and poor outcome. Despite its characteristic short half-life owing to ubiquitin-proteasome-dependent degradation, oral tumours frequently show elevated MCL-1 protein expression. Hence, we investigated the role of deubiquitinase USP9X in stabilising MCL-1 protein and its contribution to oral tumorigenesis., Methods: Expression of MCL-1 and USP9X was assessed by immunoblotting and immunohistochemistry in oral cancer cell lines and tissues. The association between MCL-1 and USP9X was confirmed by coimmunoprecipitation and immunofluorescence. Cell death assessment was performed by MTT, flow cytometry and clonogenic assays., Results: Both USP9X and MCL-1 are significantly elevated in oral premalignant lesions and oral tumours versus normal mucosa. USP9X interacts with and deubiquitinates MCL-1, thereby stabilising it. Pharmacological inhibition of USP9X potently induced cell death in OSCC cells in vitro and in vivo. The elevated expression of USP9X and MCL-1 correlated with poor prognosis in OSCC patients., Conclusion: We demonstrate the oncogenic role of USP9X in driving early-to-late stages of oral tumorigenesis via stabilisation of MCL-1, suggesting its potential as a prognostic biomarker and therapeutic target in oral cancers., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Aim: To compare the mid-term oncological results between patients with low rectal cancer who underwent minimally invasive laparoscopic surgery (MILS) and those who underwent open surgery (OS)., Patients and Methods: Overall, 262 matched patients who underwent primary resection for low rectal cancer between 2000 and 2019 were divided into MILS (n=131; n=107, conventional laparoscopic surgery; n=24, robotic surgery) and OS (n=131) groups. The short- and mid-term outcomes were compared., Results: Similar baseline characteristics were noted. The operative time was longer and blood loss was lesser in the MILS group; the conversion rate was 3.8%. The incidence of postoperative complications was similar. The 2-year cumulative incidence of local recurrence was noted to be much lower in the MILS group (1.9%) than in the OS group (8.4%). MILS had a significantly low hazard ratio (0.208, p=0.036)., Conclusion: MILS has potential benefits in reducing local recurrence of low rectal cancer., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Clusterin (CLU), a multifunctional chaperonic glycoprotein associated with diverse cellular functions has been shown to act as an oncogene or tumour suppressor gene in different cancers, implying a dual role in tumorigenesis. Here, we investigated the expression of CLU isoforms, their subcellular localization and functional significance in oral cancer cells. Significant downregulation of secretory CLU (sCLU) transcripts was observed in oral cancer cell lines and tumours versus normal cells while the nuclear CLU (nCLU) transcripts were undetectable. We demonstrated for the first time the nucleolar localization of sCLU, its response to different nucleolar stresses and association with cajal bodies post nucleolar stress. Functionally, knockdown of CLU revealed its negative association with ribosome biogenesis implying a possible tumour suppressor like role in oral cancers. Further, loss of sCLU in these cells also resulted in altered nuclear morphology and shrunken tubulin filaments. In addition, the levels of nucleolar Nucleophosmin 1(NPM1) and Fibrillarin, known to regulate nuclear morphology were downregulated indicating a possible role of sCLU in their stabilization. Further, an in silico docking approach to gain insights into the interaction of sCLU with nucleolar proteins NPM1, Fibrillarin, UBF and Nucleolin, revealed the involvement of a conserved region comprising of amino acid residues 140-155 of sCLU β-chain, specifically via the Phe152 residue in hydrophobic interactions with these client nucleolar proteins indicating a possible stabilizing or regulatory role of sCLU. SIGNIFICANCE OF THE STUDY: This is the first study to demonstrate the nucleolar localization of sCLU and its associated functions in oral cancer cells. Downregulation of sCLU in oral cancer tissues and cell lines, and its negative association with ribogenesis suggest its tumour suppressor like role in oral cancers. The possible role of sCLU in stabilization or regulation of different nucleolar proteins thereby impacting their functions is also implicated., (© 2020 John Wiley & Sons Ltd.)

Importance: Psychological reactions to perinatal loss, although often self-limited, may lead to significant psychological morbidities. Obstetrician-gynecologists and other maternal health providers play a key role in recognizing the range of psychological responses to perinatal loss and providing education, support, and treatment options to their patients., Objective: This review aims to define psychological reactions associated with perinatal loss, examine psychotherapy and psychopharmacologic treatments for psychiatric morbidities, discuss interpregnancy interval following perinatal loss, and highlight brief, psychological interventions that can be implemented by maternal health providers., Evidence Acquisition: Search terms "perinatal loss psychology," "reproductive loss grief," "perinatal psychopharmacology," "psychopharmacology grief," and "interpregnancy interval" were utilized to search PubMed, Google Scholar, and PsycINFO., Results: Grief is an expected, normal response to perinatal loss. Psychological morbidities, including major depressive disorder, generalized anxiety disorder, and posttraumatic stress disorder, are also associated with perinatal loss. Risk factors for these conditions include history of a psychiatric illness, childlessness, unknown cause of perinatal loss, limited social support, and marital/relationship discord. Careful interviewing and brief screening measures can help identify patients who may suffer from depressive or anxiety disorders following reproductive loss. Patients with perinatal loss can benefit from psychological and possibly pharmacologic treatments. Recommended interpregnancy interval after perinatal loss should be customized by gestational age and cause of loss., Conclusions and Relevance: Patients with perinatal loss emotionally benefit from their reproductive health care providers acknowledging the psychological aspects of reproductive loss, inquiring about their emotional needs, and providing information regarding grief and mental health referrals.

Background: This study aimed to investigate the short-term and oncological impact of the Endoscopic Surgical Skill Qualification System (ESSQS) by the Japan Society for Endoscopic Surgery on the operator performing laparoscopic surgery for colon cancer., Methods: This retrospective cohort study was based on medical records from a multicentre database. A total of 417 patients diagnosed with stage II/III colon and rectosigmoid cancer treated with curative resection were divided into two groups according to whether they were operated on by qualified surgeons (Q group, n=352) or not (NQ group, n=65). Through strict propensity score matching, 98 cases (49 in each group) were assessed., Results: Operative time was significantly longer in the NQ group than in the Q group (199 vs. 168 min, p=0.029). The amount of blood loss, post-operative complications, and duration of hospitalisation were similar between both groups. No mortality was observed. One conversion case was seen in the NQ group. The 3-year recurrence-free survival rate was 86.6% in the NQ group and 88.2% in the Q group, which was not statistically significant (log-rank p=0.966)., Conclusion: Direct operation by ESSQS-qualified surgeons contributed to a shortened operation time. Under an organised educational environment, almost equivalent safety and oncological outcomes are expected regardless of the surgeon's qualifications.

Background: Most evidence regarding lateral lymph node dissection for rectal cancer is from expert settings. This study aimed to evaluate the safety and efficacy of this procedure in a practice-based cohort., Methods: A total of 383 patients who were diagnosed with stage II-III mid-to-low rectal cancer between 2010 and 2019 and underwent primary resection with curative intent at a general surgery unit were retrospectively reviewed. After propensity matching, 144 patients were divided into the following groups for short- and long-term outcome evaluation: mesorectal excision with lateral lymph node dissection (n = 72) and mesorectal excision (n = 72)., Results: This practice-based cohort was characterized by a high pT4 (41.6%) and R1 resection (10.4%) rate. Although the operative time was longer in the lateral dissection group (349 min vs. 237 min, p < 0.001), postoperative complications (19.4% vs. 16.7%, p = 0.829), and hospital stay (18 days vs. 22 days, p = 0.059) did not significantly differ; 5-year relapse-free survival (62.5% vs. 66.4%, p = 0.378), and cumulative local recurrence (9.7% vs. 15.3%, p = 0.451) were also in the same range in both groups. In the seven locally recurrent cases in the lateral dissection group, four had undergone R1 resection., Conclusions: Lateral lymph node dissection was found to be safe in this practice-based cohort; however, the local control effect was not obvious. To maximize the potential merits of lateral lymph node dissection, strategies need to be urgently established to avoid R1 resection in clinical practice.