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Anastomotic leakage (AL) is a serious complication after esophagectomy for esophageal cancer. The objective of this study was to identify the risk factors for AL.Patients with esophageal cancer who underwent curative esophagectomy and cervical esophagogastric anastomosis between 2009 and 2019 (N = 346) and those between 2020 and 2022 (N = 17) were enrolled in the study to identify the risk factors for AL and the study to assess the association between the risk factors and blood flow in the gastric conduit evaluated by indocyanine green (ICG) fluorescence imaging, respectively.AL occurred in 17 out of 346 patients (4.9%). Peptic or endoscopic submucosal dissection (ESD) ulcer scars were independently associated with AL (OR 6.872, 95% CI 2.112-22.365) in addition to diabetes mellitus. The ulcer scars in the anterior/posterior gastric wall were more frequently observed in patients with AL than in those without AL (75.0% vs. 17.4%, P = 0.042). The median flow velocity of ICG fluorescence in the gastric conduits with the scars was significantly lower than in those without the scars (1.17 cm/s vs. 2.23 cm/s, P = 0.004).Peptic or ESD ulcer scarring is a risk factor for AL after esophagectomy in addition to diabetes mellitus. The scars in the anterior/posterior gastric wall are significantly associated with AL, impairing blood flow of the gastric conduit. Preventive interventions and careful postoperative management should be provided to minimize the risk and severity of AL in patients with these risk factors.

While proximal gastrectomy is being performed increasingly frequently for the treatment of gastric cancer, a standard reconstruction method to obtain optimal postoperative quality of life (QOL) still remains to be established. We modified the original esophagogastrostomy technique by introducing an additional posterolateral fundoplication (PLF) technique to minimize the risk of reflux esophagitis in patients undergoing proximal gastrectomy. The aim of this study was to clarify the clinical benefit of PLF.A retrospective analysis of the database was conducted to evaluate the effects of PLF. The data were compared between 44 patients in whom PLF was performed (PLF group) and 17 patients in whom conventional esophagogastrostomy without PLF was performed (C group). A number of incidence of postoperative reflux esophagitis and symptoms were assessed by findings of endoscopic examination and the PGSAS-45 questionnaire, respectively.The incidence of grade B or worse esophagitis after surgery was significantly lower in the PLF group than in the C group (0% vs. 58.8%, P 0.01). The score for the esophageal reflux subscale, as the main outcome measure of PGSAS-45, was significantly better in the PLF group (PLF: 1.5 vs C: 2.4, P 0.01). Cohen's d value was 1.75, which suggested a rather large effect size. Postoperative benign anastomotic stricture was encountered in 10 cases (22.7%) of the PLF group and 4 cases (23.5%) of the C group, all of whom were successfully treated by brief endoscopic mechanical dilatation.PLF is an expedient procedure for reconstruction after proximal gastrectomy.

International audience; Purpose The prevalence of parental burnout, a condition that has severe consequences for both parents and children, varies dramatically across countries and is highest in Western countries characterized by high individualism.Method In this study, we examined the mediators of the relationship between individualism measured at the country level and parental burnout measured at the individual level in 36 countries (16,059 parents). Results The results revealed three mediating mechanisms, that is, self-discrepancies between socially prescribed and actual parental selves, high agency and self-directed socialization goals, and low parental task sharing, by which individualism leads to an increased risk of burnout among parents.Conclusion The results confirm that the three mediators under consideration are all involved, and that mediation was higher for self-discrepancies between socially prescribed and actual parental selves, then parental task sharing, and lastly selfdirected socialization goals. The results provide some important indications of how to prevent parental burnout at the societal level in Western countries.

Background Neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). Chemoradiotherapy (CRT) is an alternative treatment approach. However, both treatments are associated with toxicity, and the optimal treatment for older patients with ESCC is unknown. This study aimed to evaluate the treatment strategies and prognosis of older patients with locally advanced ESCC in a real-world setting. Methods We retrospectively evaluated 381 older patients (≥ 65 years) with locally advanced ESCC (stage IB/II/III, excluding T4) who received anticancer therapy at 22 medical centers in Japan. Based on age, performance status (PS), and organ function, the patients were classified into two groups: clinical trial eligible and ineligible groups. Patients aged ≤ 75 years with adequate organ function and a PS of 0–1 were categorized into the eligible group. We compared the treatments and prognoses between the two groups. Results The ineligible group had significantly shorter overall survival (OS) than the eligible group (hazard ratio [HR] for death, 1.65; 95% confidence interval [CI], 1.22–2.25; P = 0.001). The proportion of patients receiving NAC followed by surgery was significantly higher in the eligible group than in the ineligible group (P = 1.07 × 10–11), whereas the proportion of patients receiving CRT was higher in the ineligible group than in the eligible group (P = 3.09 × 10–3). Patients receiving NAC followed by surgery in the ineligible group had comparable OS to those receiving the same treatment in the eligible group (HR, 1.02; 95% CI, 0.57–1.82; P = 0.939). In contrast, patients receiving CRT in the ineligible group had significantly shorter OS than those receiving CRT in the eligible group (HR, 1.85; 95% CI, 1.02–3.37; P = 0.044). In the ineligible group, patients receiving radiation alone had comparable OS to those receiving CRT (HR, 1.13; 95% CI, 0.58–2.22; P = 0.717). Conclusions NAC followed by surgery is justified for select older patients who can tolerate radical treatment, even if they are old or vulnerable to enrollment in clinical trials. CRT did not provide survival benefits over radiation alone in patients ineligible for clinical trials, suggesting the need to develop less-toxic CRT.

Purpose:Impacted common bile duct stones cause severe acute cholangitis. However, the early and accurate diagnosis, especially iso-attenuating stone impaction, is still challenging. Therefore, we proposed and validated the bile duct penetrating duodenal wall sign (BPDS), which shows the common bile duct penetrating the duodenal wall on coronal reformatted computed tomography (CT), as a novel sign of stone impaction., Results:A total of 40 patients (mean age 70.6 years; 18 female) were enrolled. The BPDS was observed in 15 patients. Stone impaction occurred in 13/40 (32.5%) cases. Overall accuracy, sensitivity, and specificity were 34/40 (85.0%), 11/13 (84.6%), and 23/27 (85.2%), respectively; 14/16 (87.5%), 5/6 (83.3%), and 9/10 (90.0%) for iso-attenuating stones; and 20/24 (83.3%), 6/7 (85.7%), and 14/17 (82.4%) for high-attenuating stones. Interobserver agreement of the BPDS was substantial (κ = 0.68). In addition, the BPDS was significantly correlated with the number of factors in the systemic inflammatory response syndrome (P = 0.03) and total bilirubin (P = 0.04)., Conclusion:The BPDS was a unique CT imaging finding to identify common bile duct stone impaction regardless of stone attenuation with high accuracy.

Background Following the establishment of the anti-cancer effect of immune checkpoint inhibitors, lymphopenia has attracted attention as a parameter of preexisting cancer-related immune tolerance. Although the pretreatment absolute lymphocyte count (ALC) has been reported as a prognostic factor in gastric cancer patients, the impact of perioperative changes in the ALC remains unknown. The aim of the present study was to explore the relationship between surgery-induced lymphopenia and outcome. Methods Database entries for 584 patients who underwent curative resections for pathological Stage IB-III gastric cancer were reviewed. We retrospectively compared clinicopathological factors including pretreatment ALC (pre-ALC) and ALC at first visit after discharge (post-ALC) with the survival. The low ALC was defined as Results The ALC decreased significantly at 1 and 3 days after surgery and then recovered to the baseline value. A low pre-ALC (p p p = 0.01), age, gender, BMI, T disease, N disease, severe vessel invasion, type of gastrectomy and postoperative morbidity as independent factors. The low post-ALC group had a poor RFS among patients with Stage II (p = 0.04) and Stage III (p = 0.04) disease, but not among patients with Stage IB disease (p = 0.13). Consistently, the overall survival (OS) rate was significantly lower among patients with a low post-ALC for all stage (p p = 0.02) and stage III (p = 0.01) disease, not for stage IB (p = 0.09). A low post-ALC was identified as an independent factor for predicting OS by multivariate analysis (hazard ratio: 2.275, 95% CI 1.373–3.769, p = 0.01). Conclusions A decrease in post-ALC was correlated with both of RFS and OS after curative resection in patients with locally advanced gastric cancer. Highlights Postoperative lymphopenia was a poor prognostic factor for gastric cancer.

Background Recent improvements in systemic chemotherapy have provided an opportunity for patients with stage IV gastric cancer (GC) to undergo conversion surgery (CS). The aim of this study was to evaluate the long-term outcomes of patients who underwent CS and to elucidate the prognostic factors for CS in stage IV GC. Methods A total of 79 patients who underwent CS with the aim of R0 resection for stage IV GC at six institutions from January 2008 to July 2019 were enrolled. We retrospectively reviewed the clinicopathological data and prognosis. Results Of the 79 patients, 23 (31.1%) had initially resectable disease (IR) before chemotherapy, defined as positive for cancer on peritoneal cytology (CY1), resectable hepatic metastasis, or para-aortic lymph node No. 16a2/b1 metastasis. Of the 56 remaining patients with primary unresectable disease, 39 had peritoneal dissemination. R0 resection was accomplished in 63 patients (79.7%). The 3-year OS rates for patients with IR and unresectable disease were 78.3% and 44.5%, respectively. Multivariate analysis showed that IR (P = 0.014) and R0 (P = 0.014) were statistically significant independent prognostic factors for favorable OS. Among patients with peritoneal dissemination alone, OS was significantly better for patients with R0 resection than for patients with R1/2 resection, with the 3-year OS rates of 65.5% and 23.1%, respectively (P = 0.011). Conclusions CS is a treatment option for selected patients with stage IV GC. Patients with IR and patients who achieve R0 resection may obtain a survival benefit from CS.

Cranial endocasts are one of the most direct tools available to obtain information about the endocranial cavity of fossil mammals, but few anatomical comparisons have analyzed endocranial data within a phylogenetic framework. Our study combines analyses of new digital endocasts from high-resolution X-ray micro-computed tomography (µCT) for two notoungulates, Cochilius sp. and Notostylops murinus, with data from published anatomical descriptions and endocasts (prior µCT digital endocasts and natural and extracted plaster endocasts), resulting in 22 endocranial characters (11 new) scored on 20 notoungulates and five outgroups. These data permitted a comparative study of cranial endocasts of notoungulates, an enigmatic group of extinct South American mammals, shedding light on several important issues concerning their phylogenetic relationships. The new endocranial data were integrated into a craniodental and postcranial matrix, resulting in 259 characters across 65 taxa, the most comprehensive character and taxon sampling to date and the only one including a substantial suite of endocranial characters. We further performed ancestral state reconstructions for endocranial characters using parsimony optimization on the resulting phylogenetic trees. Body mass estimates and endocranial volumes were used to calculate Encephalization Quotients (EQs) and Phylogenetic Encephalization Quotients (PEQs), which then were optimized onto the phylogenies. Endocast data from ancestral character state reconstructions bear on relationships among meridiungulates, revealing that many endocast characters may be synapomorphies for Notoungulata and other clades within the group. Notoungulates, in general, display relatively low EQs when compared with Holarctic herbivorous mammals, potentially due to their long history of evolution in isolation in South America during the Cenozoic.

The community land model version 4.5 provides two ways for treating the vegetation cover changes (a static versus an interactive) and two runoff schemes for tracking the soil moisture changes. In this study, we examined the sensitivity of the simulated boreal summer potential evapotranspiration (PET) to the aforementioned options using a regional climate model. Three different experiments with each one covering 16 years have been performed. The two runoff schemes were designated as SIMTOP (TOP) and variable infiltration capacity (VIC). Both runoff schemes were coupled to the carbon–nitrogen (CN) module, thus the vegetation status can be influenced by soil moisture changes. Results show that vegetation cover changes alone affect considerably the simulated 2-m mean air temperature (T2M). However, they do not affect the global incident solar radiation (RSDS) and PET. Conversely to the vegetation cover changes alone, the vegetation-runoff systems affect both the T2M and RSDS. Therefore, they considerably affect the simulated PET. Also, the CN-VIC overestimates the PET more than the CN-TOP compared to the Climatic Research Unit observational dataset. In comparison with the static vegetation case and CN-VIC, the CN-TOP shows the least bias of the simulated PET. Overall, our results show that the vegetation-runoff system is relevant in constraining the PET, though the CN-TOP can be recommended for future studies concerning the PET of tropical Africa.

The COVID-19 pandemic caught the world unprepared, with containment measures impacting both global supply chains and agri-commodity flows. The public health crisis raised some urgent questions: “how can fish and other aquatic foods and supply chains be prioritized as health-related interventions to avert both a malnutrition crisis and gender inequality?” Furthermore, “what are the integrated responses, investment opportunities, and governance mechanisms to effectively address the pandemic?” As “super foods,” diets of fish and aquatic foods provide animal-source protein, omega-3 fatty acids, and micronutrients, including both vitamins and minerals, necessary for both the ill and the healthy. The affordability and accessibility of fish could address food and nutrition security needs under lockdown and border closures, boost immune systems, and increase commodity trade. This analytical piece focuses on the continent of Africa, where malnutrition is pervasive, but also where local aquatic food supplies can be utilised during lockdowns and border closures. The paper provides governance insights on national budget support programs and portfolio restructuring to strengthen local aquatic foods production systems to meet dietary needs. Furthermore, the authors advocate for a coordinated multi-sectoral intervention across several well-being domains in the immediate and medium-term involving various partnerships. These integrated responses will mutually limit the contagion while providing support to functional fish value chains for healthy diets, livelihoods, cross-border trade, and long-term macroeconomic recovery.

Serial changes of focal uptake in whole-body dynamic positron emission tomography (PET) imaging were assessed and compared with those in early-delayed imaging to differentiate pathological uptake from physiological uptake in the colorectal area, based on the change in uptake shape. In 60 patients with at least 1 pathologically diagnosed colorectal cancer or adenoma, a serial 3 min dynamic whole-body PET/computed tomography imaging was performed four times around 60 min after the administration of 18F-fluorodeoxyglucose (FDG) to create a conventional (early) image by summation. Delayed imaging was performed separately at 110 min after FDG administration. High focal uptake lesions in the colorectal area were visually assessed as “changed” or “unchanged” on serial dynamic imaging and early-delayed imaging, based on the alteration in uptake shape over time. These criteria on the images were used to differentiate pathological uptake from physiological uptake. In this study, 334 lesions with high focal FDG uptake were observed. Among 73 histologically proven pathological FDG uptakes, no change was observed in 69 on serial dynamic imaging and 72 on early-delayed imaging (sensitivity of 95 vs. 99%, respectively; ns). In contrast, out of 261 physiological FDG uptakes, a change in uptake shape was seen in 159 on dynamic PET imaging and 66 on early-delayed imaging (specificity of 61 vs. 25%, respectively; p

In this manuscrit, we propose two classes of M-estimates for the hyperbolic GARCH models. The first class called M-estimate is defined by minimizing of a convenient bounded loss function. The second, called BM-estimate is a modified version of the first with a mechanism that limits the propagation of the effect of outliers in the conditional variance. The asymptotic properties of these classes of M-estimates are established. According to the Monte Carlo study, we compare the performance of the M and BM-estimates with that of the quasi-maximum likelihood (QML) estimate. We show that the proposed M and BM-estimates are less affected by outliers than the QML-estimate. Moreover, in the last part, an empirical example indicates that the studied M-estimate is the best for the out-of-sample forecasting.

Acute myeloid leukemia (AML) is a devastating disease, and clinical outcomes are still far from satisfactory. Here, to identify novel targets for AML therapy, we performed a genome-wide CRISPR/Cas9 screen using AML cell lines, followed by a second screen in vivo. We show that PAICS, an enzyme involved in de novo purine biosynthesis, is a potential target for AML therapy. AML cells expressing shRNA-PAICS exhibited a proliferative disadvantage, indicating a toxic effect of shRNA-PAICS. Treatment of human AML cells with a PAICS inhibitor suppressed their proliferation by inhibiting DNA synthesis and promoting apoptosis and had anti-leukemic effects in AML PDX models. Furthermore, CRISPR/Cas9 screens using AML cells in the presence of the inhibitor revealed genes mediating resistance or synthetic lethal to PAICS inhibition. Our findings identify PAICS as a novel therapeutic target for AML and further define components of de novo purine synthesis pathway and its downstream effectors essential for AML cell survival.

The purpose of the study was to compare staging of stage II colon cancer using the number of retrieved lymph nodes (RN) to current TNM staging for stratification of prognosis. The subjects were 6307 patients with stage II colon cancer who underwent curative resection at 24 Japanese institutions. The cutoff for the number of RN was established using Akaike information criterion (AIC) values for relapse-free survival (RFS) and overall survival (OS). Comparison of survival using TNM and T + RN (TRN) staging was performed using a Cox proportional hazards regression model. AIC was lowest for 14 retrieved lymph nodes for RFS and OS. This number was used as the cutoff. In multivariate analysis, age (≥ 69), male gender, V1, CEA (> 5), pT (T4a, T4b), and RN-L were independent factors associated with RFS and OS. Six combinations of pT and RN categories were used to establish three subgroups: TRN stages IIA, IIB, and IIC. The 5-year RFS was 83.9%, 72.3%, and 71.8% in TNM stages IIA, IIB, and IIC; and 86.0%, 76.9%, and 60.3% in TRN stages IIA, IIB, and IIC. The 5-year OS was 90.0%, 81.3%, and 82.6% for the TNM stages; and 91.6%, 85.0%, and 71.9% for the TRN stages. The AIC for RFS was lower for TRN (22,318.2) than for TNM (22,390.6), and that for OS was also lower for TRN (16,285.3) than for TNM (16,355.1). Stage II colon cancer staging using the number of retrieved lymph nodes may be superior to current TNM staging for prognosis stratification.

We have previously reported a series of thiouracil analogs as bacterial SecA inhibitors. In this study, one potent thiouracil analog, SCA-15, was further evaluated for its inhibitory effects on SecA proteins and against strains of methicillin-resistant Staphylococcus aureus (MRSA) and Bacillus anthracis Sterne. SCA-15 inhibited the ion-channel activities of SecA1 with IC50 of 2.0–2.8 μM and the ATPase activities of SecA2 with IC50 of 13–20 μM, respectively. Drug affinity responsive target stability (DARTS) and protein pull-down experiments further supported SaSecA1 and SaSecA2 as the targets of the inhibitor. SCA-15 showed promising bactericidal effects against MRSA and B. anthracis Sterne. In addition, SCA-15 could at least partially overcome the effects of efflux pumps responsible for multidrug resistance. Moreover, SCA-15 also inhibited the secretion of several important toxins of both S. aureus and B. anthracis. These results indicated that targeting SecA is a promising antimicrobial strategy against MRSA and B. anthracis.