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Background The safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines have not yet been reported. We therefore aimed to report the results of a substudy within a phase 3 UK trial, by evaluating the safety, immunogenicity, and efficacy of NVX-CoV2373 when co-administered with licensed seasonal influenza vaccines. Methods We did a planned exploratory substudy as part of the randomised, observer-blinded, placebo-controlled, phase 3 trial of the safety and efficacy of the COVID-19 vaccine (NVX-CoV2373) by co-administrating the influenza vaccine at four study hospitals in the UK. Approximately, the first 400 participants meeting the main study entry criteria—with no contraindications to influenza vaccination—were invited to join the substudy. Participants of the main study were randomly assigned (1:1) to receive two intramuscular injections of either NVX-CoV2373 (5 μg) or placebo (normal saline) 21 days apart; participants enrolled into the substudy were co-vaccinated with a single (0·5 mL) intramuscular, age-appropriate (quadrivalent influenza cell-based vaccine [Flucelvax Quadrivalent; Seqirus UK, Maidenhead] for those aged 18–64 years and adjuvanted trivalent influenza vaccine [Fluad; Seqirus UK, Maidenhead] for those ≥65 years), licensed, influenza vaccine on the opposite deltoid to that of the first study vaccine dose or placebo. The influenza vaccine was administered in an open-label manner and at the same time as the first study injection. Reactogenicity was evaluated via an electronic diary for 7 days after vaccination in addition to monitoring for unsolicited adverse events, medically attended adverse events, and serious adverse events. Immunogenicity was assessed with influenza haemagglutination inhibition and SARS-CoV-2 anti-spike protein IgG assays. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed in participants who were seronegative at baseline, received both doses of study vaccine or placebo, had no major protocol deviations affecting the primary endpoint, and had no confirmed cases of symptomatic COVID-19 from the first dose until 6 days after the second dose (per-protocol efficacy population). Immunogenicity was assessed in participants who received scheduled two doses of study vaccine, had a baseline sample and at least one post-vaccination sample, and had no major protocol violations before unmasking (per-protocol immunogenicity population). Reactogenicity was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo and had data collected for reactogenicity events. Safety was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo. Comparisons were made between participants of the substudy and the main study (who were not co-vaccinated for influenza). This study is registered with ClinicalTrials.gov, number NCT04583995. Findings Between Sept 28, 2020, and Nov 28, 2020, a total of 15 187 participants were randomised into the main phase 3 trial, of whom 15 139 received treatment (7569 received dose one of NVX-CoV2373 and 7570 received dose one of placebo). 431 participants were co-vaccinated with a seasonal influenza vaccine in the substudy (217 received NVX-CoV2373 plus the influenza vaccine and 214 received placebo plus the influenza vaccine). In general, the substudy participants were younger, more racially diverse, and had fewer comorbid conditions than those in the main study. Reactogenicity events were more common in the co-administration group than in the NVX-CoV2373 alone group: tenderness (113 [64·9%] of 174 vs 592 [53·3%] of 1111) or pain (69 [39·7%] vs 325 [29·3%]) at injection site, fatigue (48 [27·7%] vs 215 [19·4%]), and muscle pain (49 [28·3%] vs 237 [21·4%]). Incidences of unsolicited adverse events, treatment-related medically attended adverse events, and serious adverse events were low and balanced between the co-administration group and the NVX-CoV2373 alone group. No episodes of anaphylaxis or deaths were reported within the substudy. Co-administration resulted in no change to influenza vaccine immune response although a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. NVX-CoV2373 vaccine efficacy in the substudy (ie, participants aged 18 to

Background Neuropathic pain in neuroimmunological disorders refers to pain caused by a lesion or disease of the somatosensory system such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). MS and NMOSD are autoimmune disorders of the central nervous system, and ≥ 50% of patients with these disorders experience chronic neuropathic pain. The currently available medications for the management of neuropathic pain have limited effectiveness in patients with MS and NMOSD, and there is an unmet medical need to identify novel therapies for the management of chronic neuropathic pain in these patients. In this review article, we summarize the role of interleukin-6 (IL-6) in the pathogenesis of MS and NMOSD and the ameliorative effects of anti–IL-6 therapies in mouse models of experimental autoimmune encephalomyelitis (EAE). Main body Intraperitoneal injection of MR16-1, an anti–IL-6 receptor (IL-6R) antibody, reduced mechanical allodynia and spontaneous pain in EAE mice, which was attributed to a reduction in microglial activation and inhibition of the descending pain inhibitory system. The effect of anti–IL-6 therapies in ameliorating neuropathic pain in the clinical setting is controversial; a reduction in pain intensity has been reported with an anti–IL-6 antibody in four studies, namely a case report, a pilot study, a retrospective observational study, and a case series. Pain intensity was evaluated using a numerical rating scale (NRS), with a lower score indicating lesser pain. A reduction in the NRS score was reported in all four studies. However, in two randomized controlled trials of another anti–IL-6R antibody, the change in the visual analog scale pain score was not statistically significantly different when compared with placebo. This was attributed to the low mean pain score at baseline in both the trials and the concomitant use of medications for pain in one of the trials, which may have masked the effects of the anti–IL-6R antibody on neuropathic pain. Conclusion Thus, anti–IL-6 therapies might have a potential to reduce neuropathic pain, but further investigations are warranted to clarify the effect of inhibition of IL-6 signaling on neuropathic pain associated with MS and NMOSD.

Pancreatic cancer has an extremely poor prognosis because of its resistance to conventional therapies. Cancer stem cell (CSC)‐targeted therapy is considered a promising approach for this disease. Epithelial‐mesenchymal transition‐inducing transcription factors (EMT‐TFs) contribute to CSC properties in some solid tumors; however, this mechanism has not been fully elucidated in pancreatic cancer. Zinc finger protein, SNAIL2 (also known as SLUG), is a member of the SNAIL superfamily of EMT‐TFs and is commonly overexpressed in pancreatic cancer. Patients exhibiting high SNAIL2 expression have a poor prognosis. In this study, we showed that the suppression of SNAIL2 expression using RNA interference decreased tumorigenicity in vitro (sphere formation assay) and in vivo (xenograft assay) in 2 pancreatic cancer cell lines, KLM1 and KMP5. In addition, SNAIL2 suppression resulted in increased sensitivity to gemcitabine and reduced the expression of CD44, a pancreatic CSC marker. Moreover, experiments on tumor spheroids established from surgically resected pancreatic cancer tissues yielded similar results. A microarray analysis revealed that the mechanism was mediated by insulin‐like growth factor (IGF) binding protein 2. These results indicate that IGFBP2 regulated by SNAIL2 may represent an effective therapeutic target for pancreatic cancer., SNAIL2 knockdown reduces tumorigenicity and resistance to gemcitabine in tumor spheroid established from resected tissue of human pancreatic cancer as well as human pancreatic cancer cell lines.

Background Using a controlled trial, this study aimed to evaluate the effectiveness of adhesive strapping to improve the natural healing rate of umbilical hernia. Methods This prospective, observational study included 128 patients from Kumamoto, Japan (97 in the adhesive strapping group, and 31 in observation group), from 2012–2015. The duration from first hospital visit to the hernia orifice closure was compared between the two groups. Result Kaplan‐Meier curves showed that the probability of umbilical hernia in the adhesive strapping group was lower until approximately 200 days, but it was not statistically significant in the log rank test. According to multivariate Cox proportional hazard models, the hazard risk of umbilical hernia in the adhesive strapping group was significantly higher within 0–60 days after adjusting for confounding factors such as hernial cavity and hernia orifice area (P < 0.0001). Conclusion Adhesive strapping of umbilical hernia was significantly associated with earlier closure of the hernia orifice from baseline until at least 60 days.

Background /Objectives: This study aimed to elucidate the efficacy of CT findings and perioperative characteristics to predict post-pancreatectomy hemorrhage (PPH): a critical complication after pancreaticoduodenectomy. Methods The records of 590 consecutive patients who underwent pancreaticoduodenectomy at three institutes between 2012 and 2018 were included. The presence of a vascular wall abnormality or ascites with high density (vascular abnormality) on postoperative day (POD) 5–10 contrast-enhanced CT (early CT), perioperative characteristics, and any PPH or pseudoaneurysm formation (PPH events) were analyzed through a multivariate analysis. Results PPH events occurred in 48 out of 590 patients (8%). The vascular abnormality on early CT and the C-reactive protein (CRP) value on POD 3 were independent risk factors for PPH events after POD5 (vascular abnormality: odds ratio 6.42, p = 0.001; CRP on POD 3: odds ratio 1.17, p = 0.016). The sensitivity of vascular abnormality for PPH events was 24% (7/29), and the positive predictive value was 30% (7/23). The combination of vascular abnormality and a high CRP value (≥15.5 mg/dL) on postoperative day 3 had a higher positive predictive value of 64% (7/11) than the vascular abnormality alone. None of the seven PPH events that occurred more than one month after surgery were foreseen via early CT. Conclusion The combination of vascular abnormality and high CRP value was associated with increasing risk of PPH events after pancreaticoduodenectomy, but the low sensitivity of early CT must be noted as an important shortcoming. The normal findings on early CT could not eliminate the risk of late PPH.

Purpose We developed a novel and simple method to measure the source positions in applicators directly for high-dose-rate (HDR) brachytherapy based on Cherenkov emission imaging, and evaluated the performance. Methods The light emission from plastic applicators used in cervical cancer treatments, irradiated by an 192 Ir γ-ray source, was captured using a charge-coupled device camera. Moreover, we attached plastics of different shapes, including tapes, tubes, and plates to a metal applicator, to use as screens for the Cherenkov imaging. We determined the source positions and dwell intervals from the light profiles along with the applicator and compared these with preset values and dummy marker measurements. Results The source positions and dwell intervals measured from the light images were comparable to the dummy marker measurements and preset values. The distance from the applicator tip to the first source positions agreed with the dummy marker measurements within 0.2 mm for the plastic tandem. The dwell intervals measured using the Cherenkov method agreed with the preset values within 0.6 mm. The distances measured with three plastic types on the metal applicator also agreed with the dummy marker measurements within 0.2 mm. The dwell intervals measured using the plastic tape agreed with the preset values within 0.7 mm. Conclusions The proposed method should be suitable for rapid and easy quality assurance (QA) investigations in HDR brachytherapy, as it enables source position using a single image. The method allows for real-time, filmless measurements of the source positions to be obtained and is useful for rapid feedback in QA procedures.

We describe a “left-posterior approach” in which the important steps in laparoscopic distal pancreatectomy (LDP) for left-sided pancreatic cancer are accomplished in the direction caudal and dorsal to the pancreas. The patients who underwent LDP with a left-posterior approach at our hospital from January 2016 to April 2020 were reviewed to evaluate the short-term postoperative outcomes. In LDP, we first dissected retroperitoneal tissues above the left renal vein and superior mesenteric artery, yielding the mobilization of the pancreatic body widely. Then, the splenic artery was divided behind the ventrally lifted pancreas as an artery-first approach. The regional lymphadenectomy was performed in an en bloc manner consecutively in the same operative field. The neck of the pancreas was transected with a linear stapler after mobilization of the spleen. In nine patients (five men and four women) aged 76 years (range: 64–82 years), the operative time was 398 min (276–482 min) with the estimated blood loss of 40 ml (0–80 ml). No patients developed grade B/C pancreatic fistula or delayed gastric emptying. Postoperative complications classified as grade III in the Clavien–Dindo classification occurred in one patient (abdominal abscess). The pathology confirmed R0 resection in all patients who had pancreatic cancer (n = 5), IPMNs (n = 3), and high-grade pancreatic intraepithelial neoplasia (PanIN) (n = 1). The number of retrieved lymph nodes was 35 (11–49). The procedure with a left-posterior approach is a rational surgical technique in LDP for left-sided pancreatic cancer.

Deleted in lung and esophageal cancer 1 (DLEC1) is a tumour suppressor gene that is downregulated in various cancers in humans; however, the physiological and molecular functions of DLEC1 are still unclear. This study investigated the critical role of Dlec1 in spermatogenesis and male fertility in mice. Dlec1 was significantly expressed in testes, with dominant expression in germ cells. We disrupted Dlec1 in mice and analysed its function in spermatogenesis and male fertility. Dlec1 deletion caused male infertility due to impaired spermatogenesis. Spermatogenesis progressed normally to step 8 spermatids in Dlec1−/− mice, but in elongating spermatids, we observed head deformation, a shortened tail, and abnormal manchette organization. These phenotypes were similar to those of various intraflagellar transport (IFT)-associated gene-deficient sperm. In addition, DLEC1 interacted with tailless complex polypeptide 1 ring complex (TRiC) and Bardet–Biedl Syndrome (BBS) protein complex subunits, as well as α- and β-tubulin. DLEC1 expression also enhanced primary cilia formation and cilia length in A549 lung adenocarcinoma cells. These findings suggest that DLEC1 is a possible regulator of IFT and plays an essential role in sperm head and tail formation in mice.

Mesocellular silica foam was impregnated with tetraethylenepentamine (TEPA), diethanolamine (DEA), and their mixtures and examined as sorbents for CO2 capture. The sorbents were characterized by N2 physisorption, elemental analysis, and Fourier transform infrared spectroscopy. The effects of amine blending on the CO2 uptake, working capacity, and heat of adsorption were investigated and discussed. The experimental results showed that the heat of adsorption decreased with increasing DEA-to-TEPA ratios, but the CO2 uptake improved by the blending of TEPA and DEA. Furthermore, the DEA/TEPA blend considerably improved the regeneration properties of the sorbents. Mesocellular silica foam loaded with a mixture of 40 wt % TEPA and 30 wt % DEA exhibited a CO2 adsorption uptake of 5.91 mmol/g at 50 °C and 100 kPa with a heat of adsorption of 80 kJ/mol. Additionally, these sorbents demonstrated high cyclic stability and high selectivity toward CO2/N2 separation. In situ infrared spectroscopy investigations revealed that CO2 adsorption occurred predominantly through the formation of carbamate species for both TEPA and DEA.

To perform complete mesocolic excision with central vessel ligation, it is important to recognize the vessel anomaly and the location of the tumor. For left-sided colon cancer, the variations in the course of the left colic artery and accessary middle colic artery must be recognized preoperatively. Here, we describe our experience with a 57-year-old man who was diagnosed with sigmoid colon cancer with complicated inter-mesenteric connections between the inferior mesenteric artery (IMA) and superior mesenteric artery (SMA), possibly due to median arcuate ligament syndrome. We performed laparoscopic sigmoidectomy with low ligation of the IMA to preserve the extremely enlarged left colic artery. The total operative time was 155 minutes, and the estimated total blood loss was 10 mL. The patient was discharged on postoperative day 9 without any postoperative complications. For patients with vascular anomalies in the left-sided mesocolon, preoperatively ruling out SMA stenosis by using angiography and 3-D CT might be important.

Intravenous administration of magnesium with a short hydration regimen is recommended for patients receiving high-dose cisplatin to protect against cisplatin-induced nephrotoxicity. However, the optimal dose of magnesium supplementation has not been clarified. The aim of this trial was to investigate the safety and efficacy of a short hydration regimen with 20 mEq of magnesium supplementation for lung cancer patients receiving cisplatin-based chemotherapy. The key eligibility criteria included cytologically or histologically diagnosed lung cancer, candidacy for cisplatin-based (≥ 60 mg/m2) chemotherapy or chemoradiotherapy, no prior chemotherapy, aged 20–75 years, and adequate renal function. Cisplatin was administered with pre-hydration with 20 mEq of magnesium sulfate. Mannitol was administered just before cisplatin infusion to enforce diuresis. The primary endpoint was the proportion of patients who underwent cisplatin-based chemotherapy with a short hydration regimen with 20 mEq of magnesium supplementation without a grade 2 or higher elevation in creatinine. Forty patients with a median age of 66 years (range 35–74) were prospectively enrolled. Median baseline creatinine was 0.71 mg/dL. Median dose of cisplatin in the first cycle was 80 mg/m2. In the first cycle, no patients developed grade 2 creatinine toxicity. During the treatment period, one patient developed grade 2 creatinine elevation; thus, the proportion of patients without a grade 2 or higher elevation in creatinine was 97.5% (95% confidence interval 86.8–99.9). A short hydration regimen with 20 mEq of magnesium supplementation is safe and feasible for patients with lung cancer receiving cisplatin-based chemotherapy.

Objective Addiction-like eating (AE) is characterized by food cravings and loss of control over excessive food consumption. This study investigated the associations among emotional factors, personality traits, and AE symptoms in Asian young adults. Method This study included 6,823 Asian university students in South Korea, China, Singapore, Hong Kong/Macao, Japan, and Taiwan. Participants completed the modified Yale Food Addiction Scale (mYFAS) and scales on the Big-Five personality traits, impulsivity, anxiety, and depression. Results 6.2% of the participants met the mYFAS (DSM-IV-TR) food addiction diagnostic threshold. Participants from South Korea (7.9%) had the highest rate of food addiction, while participants from Japan (5.1%) and Taiwan (4.1%) reported the lowest rates. Emotional factors of anxiety and depression were the most robust correlates of AE symptoms, followed by country/region and personality factors of higher impulsivity, higher extraversion, and lower agreeableness. Personality correlates were region-specific. Higher impulsivity was a significant correlate for participants from South Korea and Taiwan, higher extraversion for participants from Singapore and Japan, and lower agreeableness for participants from China and Taiwan. Gender was also a significant correlate for participants from South Korea, Hong Kong/Macao, and Taiwan. Discussion Emotional and personality factors are important correlates of AE symptoms among Asian young adults.

Background Although 18 F-FDG-PET/CT is a widely used diagnostic tool for several malignancies, its efficacy in diagnosing pancreatic neuroendocrine tumors is reported to be controversial because of the short-term follow-up. Methods We retrospectively compared demographics and pathological features between 18 F-FDG-positive and -negative diseases. Additionally, we evaluated whether the avidity of 18 F-FDG-PET/CT affected earlier recurrence after curative treatment of non-functioning tumors. The median duration of observation was 65.6 months. Results Seventy-two patients were enrolled. 18 F-FDG-positive diseases were pathologically advanced and significantly associated with metastatic behavior. In a multivariate analysis, metastatic behavior and WHO tumor grade was independently associated with 18 F-FDG accumulation. Only 25% of functional tumors (4/16) and 8% of insulinomas (1/12) were 18 F-FDG-positive. In a Kaplan-Meier analysis in patients with non-functioning tumors (n = 56), 18 F-FDG-positivity was significantly correlated with poorer recurrence-free survival (RFS) but had no correlation with overall survival. In univariate analysis of factors associated with shorter RFS, male gender, prevalence of nodal metastasis, WHO tumor grade ≥G2, or 18 F-FDG-positive disease were significantly higher in patients with shorter RFS, whereas only 18 F-FDG-positivity was associated with shorter RFS in multivariate analyses. Conclusions The avidity of 18 F-FDG-PET/CT was associated with metastatic behavior of pancreatic neuroendocrine tumors and recurrence after treatment of non-functioning tumors.

Xylocarpus granatum is mangrove plant that traditionally used as face powder in Central Sulawesi, Indonesia which related to antioxidant, antiglycation and tyrosinase inhibition activities. This study aimed to evaluate the potency of X. granatum as a tyrosinase inhibitor, antiglycation, and antioxidant. The leaves, stem, stem bark, fruit flesh, fruit peel, and kernel of X. granatum were extracted using ethanol then their tyrosinase inhibition, antiglycation, and antioxidant were evaluated. Tyrosinase inhibition activity was evaluated using in vitro assay with L-tyrosine and L-DOPA as the substrate of monophenolase and diphenolase. Antiglycation activity was studied by measuring the excitation and emission fluorescence from glucose and fructose reaction with Bovine Serum Albumin. Antioxidant activity was measured using the DPPH radical scavenging assay. The result showed that the ethanolic extract of fruit flesh has higher potency as tyrosinase inhibitor (IC 50 of 393.8 mg/L and IC 50 of 448 mg/L, respectively for monophenolase and diphenolase). Antiglycation assay showed that the ethanolic extract of stem bark provides the strongest antiglycation activity with an IC 50 of 118.1 mg/L. Meanwhile, fruit peel provides the strongest antioxidant activity with an IC 50 of 5.5 mg/L. Fractionation of ethanolic extracts of each part of X. granatum tree yield fractions with lower bioactivity compared to the crude extract. Moreover, stem extract and fractions from two different locations (Tarakan and Kendari) tend to have different bioactivities strengths. The stem part of X granatum could be developed as new raw material of cosmetic product in Indonesia, while ethanol as the solvent for extraction, and the different bioactivity of stem extract from different location can be the consideration for the industry to standardize the extract prior to production of final product.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a brainstem predominant lymphocytic inflammatory disease, which often relapses without oral immunosuppressants. This report describes a 37-year-old male case of CLIPPERS without relapse for 1 year after early steroid treatment. He was admitted to our hospital because of sensory disturbance in the left side of his body and ataxic gait. Gadolinium-enhanced T

The object of this study is to evaluate the long-term outcome of hind limb weight-bearing function and progression of stifle osteoarthritis (OA) after tibial plateau leveling osteotomy (TPLO). Groups were classified by the degree of cranial cruciate ligament (CrCL) damage and presence or absence of medial meniscus damage as macroscopically evaluated during surgery. Weight-bearing function was assessed via the peak vertical force (PVF), and OA progression was assessed via the radiographic OA score (OAS) preoperatively and 1, 3, 6, 12, 18, 24, and 36 months postoperatively. In all stifles, PVF was significantly higher within 6 months postoperatively than preoperatively, and this high ratio was maintained for 36 months. The OAS was significantly higher 24 months postoperatively than preoperatively in stifles with a partial CrCL tear, and significantly increased at each timepoint after 3 months postoperatively in stifles with complete CrCL rupture. The OAS remained consistently lower in stifles with a partial CrCL tear and no treatment of the medial meniscus than in stifles with complete rupture. Thus, after TPLO, the weight-bearing function improved in the early postoperative period and was maintained for as long as 36 months. Although OA progressed over time after TPLO, the progression was more gradual in stifles with partial tears than in those with complete rupture. Canine patients would benefit from earlier surgical intervention through development of technology that enables early detection of ligament degeneration.

Foreign body asphyxia is a serious clinical problem with high morbidity and mortality rates. It is relatively common among children, especially those younger than 3 years, because they have a high risk of aspirating foreign bodies owing to their tendency to place objects in their mouth and lack of a well-developed swallowing reflex. Moreover, the neurologic outcome after out-of-hospital cardiac arrests (OHCA) in pediatric patients remains generally poor. Here, we report an unusual pediatric case of asphyxial OHCA caused by foreign bodies obstructing the airway, complicating esophageal foreign body, with a neurologically favorable outcome. This case highlights the importance of adequate treatment for pediatric patients with OHCA, as well as the prompt and efficient management for pediatric patients with foreign bodies obstructing the airway and esophagus.

It remains unclear whether severe liver immune-related adverse events (liver-irAEs) can affect the prognosis in non-small cell lung carcinoma (NSCLC) patients. Of the 365 NSCLC patients treated with immune checkpoint inhibitors (ICIs), 19 suffered from severe liver-irAEs (grade ≥3). The median time-to-onset of liver-irAEs was 53 days post-injection of the first ICI. The progression-free survival and overall survival of the liver-irAEs group (median 69 and 262 days, respectively) were significantly worse than the non-liver-irAEs group (128 and 722 days; P = 0.010 and P = 0.007; respectively). In conclusion, liver-irAEs were associated with poor prognosis in NSCLC patients.

The scientific and technical advances continue to support novel discoveries by allowing scientists to acquire new insights into the structure and properties of matter using new tools and sources. Notably, neutrons are among the most valuable sources in providing such a capability. At the Institute of Laser Engineering, Osaka, the first steps are taken towards the development of a table-top laser-driven neutron source, capable of producing a wide range of energies with high brightness and temporal resolution. By employing a pure hydrogen moderator, maintained at cryogenic temperature, a cold neutron ([Formula: see text]) flux of [Formula: see text]/pulse was measured at the proximity of the moderator exit surface. The beam duration of hundreds of ns to tens of [Formula: see text] is evaluated for neutron energies ranging from 100s keV down to meV via Monte-Carlo techniques. Presently, with the upcoming J-EPoCH high repetition rate laser at Osaka University, a cold neutron flux in orders of [Formula: see text] is expected to be delivered at the moderator in a compact beamline.

The broadening in species' thermal tolerance limits and breadth from tropical to temperate latitudes is proposed to reflect spatial gradients in temperature seasonality, but the importance of seasonal shifts in thermal tolerances within and across locations is much less appreciated. We performed thermal assays to examine the maximum and minimum critical temperatures (CTmax and CTmin , respectively) of a mosquito community across their active seasons. Mosquito CTmin tracked seasonal shifts in temperature, whereas CTmax tracked a countergradient pattern with lowest heat tolerances in summer. Mosquito thermal breadth decreased from spring to summer and then increased from summer to autumn. We show a temporal dichotomy in thermal tolerances with thermal breadths of temperate organisms in summer reflecting those of the tropics ("tropicalization") that is sandwiched between a spring and autumn "temperatization." Therefore, our tolerance patterns at a single temperate latitude recapitulate classical patterns across latitude. These findings highlight the need to understand the temporal and spatial components of thermotolerance variation better, including plasticity and rapid seasonal selection, and the potential for this variation to affect species responses to climate change. With summers becoming longer and increasing winter nighttime temperatures, we expect increasing tropicalization of species thermal tolerances in both space and time.

NLRP3 inflammasomes play crucial roles in the initiation of host defense by converting pro-Caspase-1 to mature Caspase-1, which in turn processes immature IL-1β and IL-18 into their biologically active forms. Although NLRP3 expression is restricted to monocytic lineages such as monocytes, macrophages, and dendritic cells, the mechanisms determining the lineage-specific expression of NLRP3 remain largely unknown. In this study, we investigated the transcription factors involved in cell-type-specific transcription of NLRP3. We found that a distal, rather than a proximal, promoter of human NLRP3 was predominantly used in the human monocytic cell lines and macrophages. Reporter analysis showed that an Ets/IRF composite element (EICE) at -309/-300 and an Ets motif at +5/+8 were critical for transcriptional activity of the distal promoter. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays demonstrated that two transcription factors, PU.1 and IRF8, both of which play essential roles in development and gene expression of the monocytic lineage, were bound to the EICE site, whereas PU.1 alone was bound to the Ets site. Knockdown of PU.1 and/or IRF8 mediated by small interfering RNA downregulated expression of NLRP3 and related molecules and markedly diminished the LPS-induced release of IL-1β in THP-1, suggesting that activity of the NLRP3 inflammasome was suppressed by knockdown of PU.1 and IRF8. Taken together, these results indicate that PU.1 and IRF8 are involved in the monocytic lineage-specific expression of NLRP3 by binding to regulatory elements within its promoter and that PU.1 and IRF8 are potential targets for regulating the activity of the NLRP3 inflammasome.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare congenital anomaly that results in Müllerian agenesis that affects the uterus and upper two-thirds of the vagina. Sigmoid vaginoplasty is a surgical treatment option; however, vaginal prolapse may result as a complication of the sigmoid neovagina. There are no standards for treatment due to the rarity of this condition. We present the case of a 59-year-old woman with a history of sigmoid vaginoplasty who underwent laparoscopic sacrocolpopexy (LSC) for grade IV sigmoid stump prolapse. The patient had a successful outcome and no evidence of recurrent prolapse. This clinical case reveals the feasibility of LSC as a surgical treatment for sigmoid stump prolapses in patients with MRKH syndrome., Highlights • There is no gold standard treatment for neovaginal prolapse, due to its rarity. • Laparoscopic sacrocolpopexy (LSC) can be considered as an optimal treatment of choice for neovaginal prolapse. • LSC for sigmoid stump prolapse in a patient with MRKH syndrome results to a good functional and anatomical outcome at 3-year follow up.

Highlights • Hepatocellular carcinoma (HCC) with duodenal invasion is a very rare occurrence. • Aggravated disease condition of HCC with duodenal invasion usually makes surgical treatment not advisable. • We present the first case of HCC with duodenal invasion resected following a multimodal therapy that included sorafenib. • Partial hepatectomy in conjunction with partial duodenectomy was selected to lessen surgical stress. • Surgical resection should be taken into consideration as a therapeutic choice even in progressive HCC disease condition., Introduction Gastrointestinal (GI) involvement in hepatocellular carcinoma (HCC) is uncommon. In particular, HCC with duodenal invasion is known to be a rare condition. In such cases, surgical indication has been generally negative except in few reported cases. To our knowledge, this report describes the first case of HCC with duodenal invasion, resected by hepatectomy accompanied by pancreas-preserving partial duodenectomy (HPPD) following multimodal therapies including systemic sorafenib administration. Case presentation A 65-year-old man had been repeatedly treated for multiple HCCs by transarterial chemoembolization (TACE) and sorafenib. However, the main tumor formerly ruptured began to involve his duodenum, causing GI bleeding. The collateral vessels from the pancreatic and omental branches entered the tumor and nullified the transarterial hemostatic embolization. Hence, HPPD was performed to preserve the major Vater papilla. Histopathological examination revealed poorly-to -moderately differentiated HCC cells invading the duodenum. Discussion and conclusion HPPD treatment successfully removed HCC with duodenal invasion achieving viable tumor clearance status (R0). We underline the importance of achieving viable tumor clearance status at any time during the treatment course of patients with advanced HCC as this approach may be the only approach to enable HCC patients with duodenal invasion to resume a healthy life.

The urinary bladder is protected by the pelvic bones and hence is a site less susceptible to external force injury than other organs. As children’s bones are not fully developed, the risk of bladder injury by external force is greater in children than adults. Pelvic fractures often cause the bladder to rupture, as do strong external forces when the bladder is filled. Bladder rupture is categorized as extraperitoneal or intraperitoneal, and treatments differ between the two. Extraperitoneal injury usually heals after drainage alone, whereas intraperitoneal injury usually requires surgical intervention such as a combination of surgical repairs and drainage. Herein, we report a pediatric case of intraperitoneal bladder rupture successfully treated without surgical repair (i.e., with drainage via an intraperitoneal tube and a urethral catheter only). Our report suggests that nonoperative treatment is an option for pediatric patients with intraperitoneal bladder rupture if certain conditions are met.

Background Visceral obesity is one of the risk factors for clinically relevant pancreatic fistula after pancreatic resection. The objective of this study was to evaluate the impact of intraperitoneal lipolysis on postoperative pancreatic fistula. Methods The degree of intraperitoneal lipolysis was investigated by measuring the free fatty acid concentration in drain discharge in patients after pancreatic resection. An experimental pancreatic fistula model was prepared by pancreatic transection, and the impact of intraperitoneal lipolysis was evaluated by intraperitoneal administration of triolein (triglyceride) with, or without orlistat (lipase inhibitor). Results Thirty-three patients were included in the analysis. The free fatty acid concentration in drain discharge on postoperative day 1 was significantly associated with the development of a clinically relevant pancreatic fistula (P = 0·004). A higher free fatty acid concentration in drain discharge was associated with more visceral adipose tissue (P = 0·009). In the experimental model that included 98 rats, intraperitoneal lipolysis caused an increased amount of pancreatic juice leakage and multiple organ dysfunction. Intraperitoneal administration of a lipase inhibitor reduced lipolysis and prevented deterioration of the fistula. Conclusion Intraperitoneal lipolysis significantly exacerbates pancreatic fistula after pancreatic resection. Inhibition of lipolysis by intraperitoneal administration of a lipase inhibitor could be a promising therapy to reduce clinically relevant postoperative pancreatic fistula. Surgical relevance Clinically, there are two types of pancreatic fistula after pancreatic resections: harmless biochemical leak and harmful clinically relevant pancreatic fistula. Visceral obesity is one of the known risk factors for clinically relevant pancreatic fistula; however, the underlying mechanisms remained to be elucidated. Patients with clinically relevant pancreatic fistula had a higher free fatty acid concentration in the drain discharge, suggesting a relationship between intraperitoneal lipolysis and pancreatic fistula. The experimental model of pancreatic fistula demonstrated that intraperitoneal lipolysis caused deterioration in pancreatic fistula, suggesting that intraperitoneal lipolysis is one of the mechanisms that drives biochemical leakage to clinically relevant pancreatic fistula. Intraperitoneal administration of a lipase inhibitor prevented lipolysis as well as pancreatic fistula deterioration in the experimental model, suggesting a future clinical application for lipase inhibitors in prevention of clinically relevant pancreatic fistula.

Objectives This study aimed to determine the relative risks of addiction to the Internet, online gaming and online social networking of college students in six Asian countries/regions (Singapore, Hong Kong [HK]/Macau, China, South Korea, Taiwan and Japan) compared with students in the United States (US). It also explored the relative risks of depression and anxiety symptoms among students with Internet-related addictions from these countries/regions. Study design This is a cross-sectional survey. Methods A convenience sample of 8067 college students aged between 18 and 30 years was recruited from seven countries/regions. Students completed a survey about their use of the Internet, online gaming and online social networking as well as the presence of depression and anxiety symptoms. Results For all students, the overall prevalence rates were 8.9% for Internet use addiction, 19.0% for online gaming addiction and 33.1% for online social networking addiction. Compared with the US students, Asian students showed higher risks of online social networking addiction but displayed lower risks of online gaming addiction (with the exception of students from HK/Macau). Chinese and Japanese students also showed higher risks of Internet addiction compared with the US students. In general, addicted Asian students were at higher risks of depression than the addicted US students, especially among Asian students who were addicted to online gaming. Addicted Asian students were at lower risks of anxiety than the addicted US students, especially among Asian students who were addicted to online social networking, and addicted students from HK/Macau and Japan were more likely to have higher relative risks of depression. Conclusions There are country/regional differences in the risks of Internet-related addictions and psychiatric symptoms. It is suggested that country/region-specific health education programmes regarding Internet-related addictions are warranted to maximise the efficiency of prevention and intervention. These programmes should attempt to tackle not only problematic Internet-related behaviours but also mood disturbances among college students.

BACKGROUND /Objectives: Although the presence of lymph node metastasis (LNM) defines malignant potential, preoperative prediction of LNM has not been established for non-functional pancreatic neuroendocrine neoplasm (NF-PNEN). We sought to develop a prediction system using only preoperatively available factors that would stratify the risk of LNM for NF-PNEN. METHODS We retrospectively reviewed patients who underwent R0/1 resection of NF-PNEN at Kyoto University (2007-2019) and the University of California, San Francisco (2010-2019). Risk stratification of LNM was developed using preoperative factors by the logistic regression analysis. Long-term outcomes were compared across the risk groups. RESULTS A total of 131 patients were included in this study. Lymph nodes were pathologically examined in 116 patients, 23 (20%) of whom had LNM. Radiological tumor size [1.5-3.5 cm (odds ratio: 13.5, 95% confidence interval: 1.77-398) and >3.5 cm (72.4, 9.06-2257) against ≤1.5 cm]

A 25-day-old term infant presented with fever, diarrhoea and 10% wt loss since birth (figure 1A) and 80% oxygen saturation in ambient air. His heart rate was 178 beats/min and blood pressure was 64/45 mmHg. Blood tests revealed a pH of 7.0, and bicarbonate, lactate and methaemoglobin levels of 6.2 mmol/L, 5.2 mmol/L, and 21%, respectively. After rehydration with fluid for shock, administration of sodium bicarbonate and stopping formula milk, …

Prolonging the circulation time (CT) of microparticles (MPs) in the blood is key for a successful microparticle-based medicinal approach to serve as drug delivery systems (DDSs). Previously, we reported that MPs that mimic the shape of red blood cells (RBCs) avoid accumulation in the spleen and lungs. We now describe the effectiveness of mimicking not only the shape of RBCs but also their surface structure for the prolongation of CT. RBC-shaped MPs (RBC-MPs) were electrosprayed with cellulose and covered with a native RBC membrane (RBCM) collected from mouse blood. Seven hours after intravenous injection, approximately twice as many RBCM-covered RBC-MPs (RBC-MPs@RBCM) were present in the blood of mice compared to unmodified RBC-MPs. Twenty-four hours postinjection, the concentration of RBC-MPs@RBCM in the blood was 4 times higher. These findings suggest that an RBCM covering the MPs contributed to significant CT prolongation, which may positively impact their applications as DDSs.

Among 1,770 healthcare workers serving in high-risk care areas for coronavirus disease 2019 (COVID-19), 39 (2.2%) were seropositive. Exposure to severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in the community was associated with being seropositive. Job or unit type and percentage of time working with COVID-19 patients were not associated with positive antibody tests.