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Purposes: Robot-assisted thoracoscopic (RATS) segmentectomy is becoming increasingly common because of the expanded indications for segmentectomy and the widespread adoption of robotic surgery. The precise division of the intersegmental plane is necessary to ensure oncologic margins from the tumor and to preserve the lung function. In this study, we present a strategy for accurately dividing the intersegmental plane using a robotic stapler and review the surgical outcomes. Methods: RATS portal segmentectomy was performed using the Da Vinci Xi system and the intersegmental plane was dissected using a robotic stapler. We evaluated the perioperative outcomes in 92 patients who underwent RATS portal segmentectomy between May 2020 and January 2023. These results were compared with those of 82 patients who underwent complete video-assisted thoracoscopic surgery (CVATS) during the same period. Results: The operative and console times were 162 and 97 min, respectively. No intraoperative complications occurred, and postoperative complications were observed in four cases (4.3%). The operative time, blood loss, postoperative complications, and maximum incision size were significantly lower in the RATS group than in the CVATS group. However, RATS requires a significantly higher number of staplers than CVATS. Conclusions: The division of the intersegmental plane using a robotic stapler in RATS portal segmentectomy was, therefore, found to be safe and effective. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to analyze the risk factors for acute events after systemic-to-pulmonary shunt (SPS) and to investigate the effectiveness of pulmonary blood flow regulation with a metal clip. Methods: The case histories of 116 patients (78 biventricular [BV] and 38 single ventricle [SV] physiology) who underwent SPS between 2010 and 2021 were retrospectively reviewed. Our strategy was to delay SPS until 1 month of age; pulmonary blood flow (PBF) regulation by partial clipping of the graft, if needed. Cases of aortic cross-clamping were excluded from this study. Results: CPB was used in 49 (42%) patients: the median age at SPS was 1 month (2 days to 16 years), and the sternotomy approach in 65. Discharge survival was 98.3% (114/116); hospital death occurred in 1.7% due to coronary ischemia. Inter-stage mortality occurred in 1.7% (shunt thrombosis, 1; pneumonia, 1). Pre-discharge acute events occurred in 7 patients (6.0%): thrombosis 3, pulmonary over-circulation 2, and coronary ischemia 2. Multiple logistic regression analysis revealed that pulmonary atresia with intact ventricular septum (PA/IVS) (p = 0.0253) was an independent risk factor for acute events. Partial clipping of the graft was performed in 24 patients (pulmonary atresia 15) and clip removal was performed by catheter intervention in 9 patients; no coronary ischemic events and graft injury occurred in these patients. Conclusion: Surgical outcomes after SPS were acceptable and metal clip regulation of pulmonary blood flow appears to be safe and effective. PA/IVS was still a significant risk factor for acute events. [ABSTRACT FROM AUTHOR]

Main conclusion: PATOL1 contributes to increasing biomass not only by effective stomatal movement but also by root meristematic activity. PATROL1 (PROTON ATPase TRANSLOCATION CONTROL 1), a protein with a MUN domain, is involved in the intercellular trafficking of AHA1 H+-ATPase to the plasma membrane in guard cells. This allows for larger stomatal opening and more efficient photosynthesis, leading to increased biomass. Although PATROL1 is expressed not only in stomata but also in other tissues of the shoot and root, the role in other tissues than stomata has not been determined yet. Here, we investigated PATROL1 functions in roots using a loss-of-function mutant and an overexpressor. Cytological observations revealed that root meristematic size was significantly smaller in the mutant resulting in the short primary root. Grafting experiments showed that the shoot biomass of the mutant scion was increased when it grafted onto wild-type or overexpressor rootstocks. Conversely, grafting of the overexpressor scion shoot enhanced the growth of the mutant rootstock. The leaf temperatures of the grafted plants were consistent with those of their respective genotypes, indicating cell-autonomous behavior of stomatal movement and independent roles of PATROL1 in plant growth. Moreover, plasma membrane localization of AHA1 was not altered in root epidermal cells in the patrol1 mutant implying existence of a different mode of PATROL1 action in roots. Thus PATROL1 plays a role in root meristem and contributes to increase shoot biomass. [ABSTRACT FROM AUTHOR]

Purpose: Some patients who undergo anterior cruciate ligament (ACL) reconstruction experience abnormal mechanical stress in the meniscus. Medial meniscal extrusion (MME) is reflected in the pathological condition of the meniscus, which expands owing to repetitive mechanical stress. Thus, the effect of the reconstructed ACL on increasing MME under weight-bearing conditions remains unclear. This study investigated the effect of ACL reconstruction on meniscal extrusion under non-weight-bearing and weight-bearing conditions. Methods: Seventeen patients who underwent unilateral ACL reconstruction (ACL group) and 20 age-matched healthy volunteers (control group) were enrolled. Ultrasonography was performed in the supine, standing, and walking positions in preoperative and postoperative ACL patients. MME during walking was evaluated based on the dynamic behavior of extrusion, and kinetic and kinematic data were synchronously obtained. Moreover, the ACL group underwent magnetic resonance imaging (MRI) evaluation at two points: preoperatively and 12 months postoperatively, and the ultrasound findings were compared. Results: MME in the supine position measured using both ultrasonography and MRI was not significantly different preoperatively and postoperatively in the ACL group. However, postoperative MME and dynamic behavior of extrusion under standing and walking conditions were significantly higher than those in the preoperative state (dynamic behavior: 0.9 ± 0.4 mm preoperatively, 1.2 ± 0.4 mm postoperatively). Moreover, the deficits in knee extension during walking persisted postoperatively and were significantly higher than those in the control group. Conclusion: MME in patients with ACL reconstruction including meniscus repair was different under mechanical stress compared to the non-weight bearing condition. [ABSTRACT FROM AUTHOR]

Sonazoid, an ultrasound contrast agent, has been covered by insurance in Japan since January 2007 for the diagnosis of hepatic mass lesions and is widely used for diagnosing not only primary liver cancer but also liver metastases such as those from breast cancer and colorectal cancer. Contrast-enhanced ultrasound for breast mass lesions has been covered by insurance since August 2012 after phase II and phase III clinical trials showed that the diagnostic performance was significantly superior to that of B-mode and contrast-enhanced magnetic resonance imaging. This paper describes the principles of imaging techniques in contrast-enhanced ultrasonography including the filter, pulse inversion, amplitude modulation, and amplitude-modulated pulse inversion methods. The pulse inversion method, which visualizes the second-harmonic component using the nonlinear scattering characteristics of the contrast agent, is widely used regardless of the contrast agent and target organ because of its high resolution. Sonazoid has a stiffer shell and requires a higher acoustic amplitude than Sonovue to generate nonlinear vibrations. The higher transmitted sound pressure generates more tissue harmonic components. Since pulse inversion allows visualization of the tissue harmonic components, amplitude modulation and amplitude-modulated pulse inversion, which include few tissue harmonic components, are primarily used. Amplitude modulation methods detect nonlinear signals from the contrast agent in the fundamental band. The mechanism of the amplitude modulation is considered to be changes in the echo signal's phase depending on the sound pressure. Since the tissue-derived component is minor in amplitude modulation methods, good contrast sensitivity can be obtained. [ABSTRACT FROM AUTHOR]

Purpose: To investigate how revision of the organ transplant law in Japan affected lung transplantation in this country. Methods: Lung transplant candidates registered between January, 2000 and December, 2009 were designated as the pre-revision group (n = 396) and those registered between January, 2011 and December, 2020, as the post-revision group (n = 1326). Both groups were analyzed retrospectively using data collected by the Japanese Society of Lung and Heart–Lung Transplantation. Results: The number of patients who underwent brain-dead donor lung transplantation (BDLT) increased significantly after the law amendment (32.2 vs. 13.8%, p < 0.01). The median waiting time for BDLT was significantly reduced (708 days vs. 1163 days, p < 0.01) and the mortality rate while waiting for BDLT improved significantly after the law amendment (33.1 vs. 42.6%, p < 0.01). In the post-revision group, 18 pediatric patients underwent BDLT. The 5-year survival rates after BDLT were comparable between the groups (73.5% in the pre-revision group vs. 73.2% in the post-revision group, p = 0.32). Conclusions: The organ transplant law revision shortened the waiting time for BDLT significantly and decreased the mortality rate while waiting for BDLT. The posttransplant outcomes in Japan remained favorable throughout the study period. [ABSTRACT FROM AUTHOR]

Purpose: To define the clinical and histological characteristics of nephritis in patients with X-linked agammaglobulinemia (XLA) and their immunological profiles. Methods: The clinical, immunological, and histological findings of nine patients with XLA and nephritis were retrospectively analyzed. Results: Based on kidney histological findings, patients with XLA and nephritis could be divided into two groups, viz., chronic glomerulonephritis (CGN) and tubulointerstitial nephritis (TIN). The two groups showed different immunological profiles. Patients in the CGN group exhibited an atypical immunological profile of XLA, with pathogenic leaky B cells producing immunoglobulins that may play a role in forming immune complexes and causing immune-mediated glomerulonephritis. In contrast, patients in the TIN group exhibited a typical immunological profile of XLA, suggesting that antibody-independent/other BTK-dependent mechanisms, or immunoglobulin replacement therapy (IgRT)-related immune/nonimmune-mediated nephrotoxicity causes TIN. Conclusion: Nephritis occurring in patients with XLA could have links between their renal pathology and immunological status. Careful observation is recommended to detect kidney pathology in patients with XLA on IgRT. [ABSTRACT FROM AUTHOR]

We aimed to clarify the long-term safety and efficacy of rituximab (RTX) as a remission induction therapy following severe relapse in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). We retrospectively collected the data of patients with severely relapsed AAV from a Japanese multicentre cohort. The primary exposure was RTX use; the primary outcome was complete remission (CR) proportions at week 24. Baseline characteristics were compared between the RTX and non-RTX groups. We performed multivariate logistic regression analysis and one-to-one propensity score matching analysis as a sensitivity analysis. Totally, 100 patients were enrolled: 52 in the RTX group and 48 in the non-RTX group. Baseline characteristics were comparable between the two groups, except for age, AAV subtype and ANCA serotype. The median age was 71 vs. 75 years, and the PR3-ANCA positivity rate was 44.2% vs. 18.8% in the RTX and non-RTX groups, respectively. No significant difference was observed in CR proportions at week 24 between the two groups (79.2% vs. 68.1%, p = 0.321), with an adjusted odds ratio of 1.27 (95% confidence interval [CI] 0.47–3.51). At week 48, CR proportions were significantly higher in the RTX group (91.7% vs. 64.9%, p = 0.005), with an adjusted odds ratio of 2.95 (95% CI 0.97–9.91). Serious infection rates were lower in the RTX group than in the non-RTX group, with no statistically significant difference. RTX was not superior to conventional immunosuppressive therapies at week 24 but showed significantly favourable results at week 48 for severely relapsed AAV. Key Points • RTX might be superior to traditional treatments as an induction therapy for severely relapsed AAV. • RTX has the potential to sustain long-term remission with fewer occurrences of infections in the treatment of severely relapsed AAV. [ABSTRACT FROM AUTHOR]

Background: Active surveillance for prostate cancer was initiated in the early 2000s. We assessed the long-term outcomes of active surveillance in Japan. Methods: This multicenter prospective observational cohort study enrolled men aged 50–80 years with stage cT1cN0M0 prostate cancer in 2002 and 2003. The eligibility criteria included serum prostate-specific antigen level ≤ 20 ng/mL, ≤ 2 positive cores per 6–12 biopsy samples, Gleason score ≤ 6, and cancer involvement < 50% in the positive core. Patients were encouraged to undergo active surveillance. Prostate-specific antigen levels were measured bimonthly for 6 months and every 3 months thereafter. Triggers for recommending treatment were prostate-specific antigen doubling time of < 2 years and pathological progression on repeat biopsy. Results: Among 134 patients, 118 underwent active surveillance. The median age, prostate-specific antigen level at diagnosis, and maximum cancer occupancy were 70 years, 6.5 ng/mL, and 11.2%, respectively. Ninety-one patients had only one positive cancer core. The median observation period was 10.7 years. At 1 year, 65.7% underwent a repeat biopsy, and 37% of patients experienced pathological progression. The active surveillance continuation rates at 5, 10, and 15 years were 28%, 9%, and 4%, respectively. One prostate cancer-related death occurred in a patient who refused treatment despite pathological progression at the one-year repeat biopsy. Conclusion: Active surveillance according to this study protocol was associated with conversion to the next treatment without delay, when indicated, despite the selection criteria and follow-up protocols being less rigorous than those recommended in current international guidelines. [ABSTRACT FROM AUTHOR]

Hepatic glucose metabolism serves dual purposes: maintaining glucose homeostasis and converting glucose into energy sources; however, the underlying mechanisms are unclear. We quantitatively measured liver metabolites, gene expression, and phosphorylated insulin signaling molecules in mice orally administered varying doses of glucose, and constructed a transomic network. Rapid phosphorylation of insulin signaling molecules in response to glucose intake was observed, in contrast to the more gradual changes in gene expression. Glycolytic and gluconeogenic metabolites and expression of genes involved in glucose metabolism including glucose-6-phosphate, G6pc, and Pck1, demonstrated high glucose dose sensitivity. Whereas, glucokinase expression and glycogen accumulation showed low glucose dose sensitivity. During the early phase after glucose intake, metabolic flux was geared towards glucose homeostasis regardless of the glucose dose but shifted towards energy conversion during the late phase at higher glucose doses. Our research provides a comprehensive view of time- and dose-dependent selective glucose metabolism. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is the most lethal gynecologic cancer, mainly due to late diagnosis with widespread peritoneal spread at first presentation. We performed metabolomic analyses of ovarian and paired control tissues using capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry to understand its metabolomic dysregulation. Of the 130 quantified metabolites, 96 metabolites of glycometabolism, including glycolysis, tricarboxylic acid cycles, urea cycles, and one-carbon metabolites, showed significant differences between the samples. To evaluate the local and systemic metabolomic differences in OC, we also analyzed low or non-invasively available biofluids, including plasma, urine, and saliva collected from patients with OC and benign gynecological diseases. All biofluids and tissue samples showed consistently elevated concentrations of N1,N12-diacetylspermine compared to controls. Four metabolites, polyamines, and betaine, were significantly and consistently elevated in both plasma and tissue samples. These data indicate that plasma metabolic dysregulation, which the most reflected by those of OC tissues. Our metabolomic profiles contribute to our understanding of metabolomic abnormalities in OC and their effects on biofluids. [ABSTRACT FROM AUTHOR]

The control of African trypanosomiasis (AT) in Eastern and Southern Africa, including Zambia, faces huge challenges due to the involvement of wild and domestic animal reservoirs. Free-roaming dogs in wildlife-populated and tsetse-infested villages of Zambia's Mambwe district are exposed to infectious tsetse bites. Consuming fresh raw game meat and bones further exacerbates their risk of contracting AT. We focus on the reservoir role of such dogs in maintaining and transmitting diverse species of trypanosomes that are infective to humans and livestock in Zambia's Mambwe district. A cohort of 162 dogs was enrolled for follow-up at 3 different time points from June to December 2018 in selected villages of Malama, Mnkhanya, and Nsefu chiefdoms of Mambwe district, eastern Zambia. Blood and serum were screened for AT by microscopy, GM6 ELISA, PCR (ITS1 and SRA), and Sanger sequencing. Out of the 162 dogs in the cohort, 40 were lost to follow-up and only 122 remained traceable at the end of the study. GM6 ELISA detected Trypanosoma antibodies in 121 dogs (74.7%) and ITS1-PCR detected DNA involving single and mixed infections of T. congolense, T. brucei, and suspected T. simiae or T. godfreyi in 115 dogs (70.9%). The human-infective T. b. rhodesiense was detected by SRA PCR in 67 dogs (41.4%), and some sequence data that support the findings of this study have been deposited in the GenBank under accession numbers OL961811, OL961812, and OL961813. Our study demonstrates that the Trypanosoma reservoir community in Zambia is wider than was thought and includes domesticated dogs. As dogs are active carriers of human and livestock-infective trypanosomes, they pose a risk of transmitting AT in endemic villages of Mambwe district as they are neglected and left untreated. To fully bring AT under control, countries such as Zambia where the role of animal reservoirs is important, should not limit their prevention and treatment efforts to livestock (especially cattle) but also include dogs that play an integral part in most rural communities. [ABSTRACT FROM AUTHOR]

There exist many rock slopes with weak rocks in mines. However, long-term slope stability, especially for large-scale slopes with weak layers, still remains a challenging issue in mine projects. This study employed in-situ surface displacement monitoring and numerical analysis to assess excavation-induced effects on a high clay-bearing interbedded rock slope. A Japanese limestone quarry with a 250-meter-high rock slope intercalated by a 70-meter-thick clay-bearing rock at the footwall was used as a case study. The characteristics of the slope deformation, including the deformation rate, were first characterized by analyzing surface displacement measured by an automated polar system. Based on the measured data and the 2-dimensional finite element method, a back analysis of mining-induced deformation was performed to estimate the horizontal rock stress of the quarry and the Young's modulus of the clay-bearing rock. Thereafter, the elastic deformation of the rock slope induced by the excavation and the excavation-induced deterioration of the clay-bearing rock were evaluated. The results demonstrated that the deformation mechanism can be explained by both the deformation mechanism due to the excavation-induced deterioration of the clay-bearing rock and the horizontal stress release. Furthermore, vertical and horizontal advancing excavation patterns are proposed to clarify the deformation mechanism based on the incremental characteristics of distance changes. The findings provide useful insights into understanding the deformation mechanisms of excavation-induced deterioration of clay-bearing rock and the effect of excavation sequence patterns when interpreting the characteristics of measured surface displacement results in open-pit mines. [ABSTRACT FROM AUTHOR]

Purpose: Radiation pneumonitis (RP) is an obstacle for patients after surgery following induction chemoradiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC). We performed a comparative analysis of the association between clinicopathological factors, including the neutrophil-to-lymphocyte ratio (NLR) and prognosis, in LA-NSCLC patients with or without RP during induction chemoradiotherapy followed by surgery. Methods: The subjects of this analysis were 168 patients undergoing trimodality therapy for LA-NSCLC between January, 1999 and May, 2019. Patients were divided into two groups: the RP group (n = 41) and the non-RP group (n = 127). We compared the clinicopathological factors including the NLR between the groups and analyzed the association between the NLR and prognosis. Results: The RP group had more patients with tumors located in the lower lobe, more bilobar resections, shorter operative times, no implementation of postoperative adjuvant chemotherapy, and a higher postoperative NLR than the non-RP group. There were no significant differences in serious postoperative complications and the prognosis. Patients with a low postoperative NLR had a significantly better prognosis in the non-RP group, and a trend toward a better prognosis even in the RP group. Conclusion: Postoperative NLR may be a useful prognostic factor, even for patients who suffer RP after trimodality therapy for LA-NSCLC. [ABSTRACT FROM AUTHOR]

The commercial value of cookies is easily lost when they break due to mechanical stress, such as shock, during distribution. Therefore, it is important to prevent shock by incorporating a cushioning design into cookie packaging. To optimize packaging, we must first understand the type of breakage caused by shock. During distribution, fatigue failure due to repetitive shocks might be the main factor involved in breakage of cookies because events related to shock stress usually occur more than once. Accordingly, we investigated the relationships between acceleration, shock frequency, and the occurrence of breakage in two types of packaged cookies (soft and hard). A drop test was performed at heights of 0.15–0.45 m. The results suggest that both types of cookies are broken by repetitive shocks, and the relationship between the number of shocks, acceleration (related to drop height), and the occurrence of breakage can be expressed as power approximation curves. Generally, the breakage of cookies due to mechanical stress is known to be a result of brittle fractures. However, our results suggest that the visible breakage of packaged cookies due to repetitive shock may be the result of fatigue failure. In addition, we propose a simple method that uses a small accelerometer to simulate breakage during transportation. The results of this study contribute to the development of new cushioning packaging designs to reduce the breakage of cookies during transportation. [ABSTRACT FROM AUTHOR]

People living in coastal areas have the advantage of accessing a high level of ecosystem services, but are also exposed to the dangers inherent in living by the sea in an area prone to natural disasters. To achieve sustainable utilization of the high ecosystem services of coastal areas, establishment of an effective marine policy based on regional characteristics of human–nature interactions is essential. We compared the structure of perceived satisfaction for five components of human well-being ('Security', 'Basic material for a good life', 'Good social relations', 'Health', and 'Freedom of choice and action') derived from coastal ecosystem services among three sites in Japan (Wakasa, Sanriku, and Shima) that share the same natural and social backgrounds: highly dependent on fisheries industry, located in the same climate regime (temperate zone), and have similar topographical features (ria coast). Structural equation modeling using the results from questionnaire surveys showed that the three sites shared a common basic structure of the interactions among the five components of human well-being. However, the intensity of interactions among components differed among the three sites. Questionnaire surveys on anxiety about natural disasters and future access to marine ecosystem services were simultaneously conducted at the three sites. The site-specific anxieties were responsible for the difference in the interactions among the five components of human well-being. We propose a method that quantitatively evaluates both positive (satisfaction) and negative (anxiety) aspects of respondents' subjective assessment as a useful tool for understanding the diversity of human–nature interactions caused by the region-specific natural and social backgrounds of coastal areas. [ABSTRACT FROM AUTHOR]

Purpose: Preoperative chemotherapy is a critical component of breast cancer management, yet its effectiveness is not uniform. Moreover, the adverse effects associated with chemotherapy necessitate the identification of a patient subgroup that would derive the maximum benefit from this treatment. This study aimed to establish a method for predicting the response to neoadjuvant chemotherapy in breast cancer patients utilizing a metabolomic approach. Methods: Plasma samples were obtained from 87 breast cancer patients undergoing neoadjuvant chemotherapy at our facility, collected both before the commencement of the treatment and before the second treatment cycle. Metabolite analysis was conducted using capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography-mass spectrometry (LC–MS). We performed comparative profiling of metabolite concentrations by assessing the metabolite profiles of patients who achieved a pathological complete response (pCR) against those who did not, both in initial and subsequent treatment cycles. Results: Significant variances were observed in the metabolite profiles between pCR and non-pCR cases, both at the onset of preoperative chemotherapy and before the second cycle. Noteworthy distinctions were also evident between the metabolite profiles from the initial and the second neoadjuvant chemotherapy courses. Furthermore, metabolite profiles exhibited variations associated with intrinsic subtypes at all assessed time points. Conclusion: The application of plasma metabolomics, utilizing CE-MS and LC–MS, may serve as a tool for predicting the efficacy of neoadjuvant chemotherapy in breast cancer in the future after all necessary validations have been completed. [ABSTRACT FROM AUTHOR]

This study investigates the promotion of sodium chlorate (NaClO3) crystallization through optical trapping, enhanced by the addition of gold nanoparticles (AuNPs) and silicon nanoparticles (SiNPs). Using a focused laser beam at the air–solution interface of a saturated NaClO3 solution with AuNPs or SiNPs, the aggregates of these particles were formed at the laser focus, the nucleation and growth of metastable NaClO3 (m-NaClO3) crystals were induced. Continued laser irradiation caused these m-NaClO3 crystals to undergo repeated cycles of growth and dissolution, eventually transitioning to a stable crystal form. Our comparative analysis showed that AuNPs, due to their significant heating due to higher photon absorption efficiency, caused more pronounced size fluctuations in m-NaClO3 crystals compared to the stable behavior observed with SiNPs. Interestingly, the maximum diameter of the m-NaClO3 crystals that appeared during the size fluctuation step was consistent, regardless of nanoparticle type, concentration, or size. The crystallization process was also promoted by using polystyrene nanoparticles, which have minimal heating and electric field enhancement, suggesting that the reduction in activation energy for nucleation at the particle surface is a key factor. These findings provide critical insights into the mechanisms of laser-induced crystallization, emphasizing the roles of plasmonic heating, particle surfaces, and optical forces. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic simultaneous resection (LSR) of primary colorectal tumors and synchronous colorectal liver metastases (sCRLM) has been recently performed. This study aimed to evaluate the postoperative outcomes after LSR and determine the risk factors for resection surface-related complications (RSRC), such as postoperative biliary fistula and liver-transection surface abscess. Methods: Between 2009 and 2022, consecutive patients with sCRLM who underwent LSR were included. We retrospectively analyzed clinicopathological data, including intraoperative factors and postoperative outcomes. The difficulty level of all liver resections was classified according to the IWATE difficulty scoring system (DSS). We then performed univariate and multivariate analyses to identify the risk factors for RSRC. Results: Of the 112 patients, 94 (83.9%) underwent partial hepatectomy and colorectal surgery. The median DSS score was 5 points (1–11), with 12 (10.7%) patients scoring ≥ 7 points. Postoperative complications were observed in 41 (36.6%) patients, of whom 16 (14.3%) experienced severe complications classified as Clavien–Dindo grade IIIa or higher. There was no postoperative mortality. The most common complication was RSRC (19 patients, 17.0%). Multivariate analysis identified American Society of Anesthesiologists (ASA) classification ≥ 3 [odds ratio (OR) 10.3, 95% confidence interval (CI) 1.37–77.8; P = 0.023], DSS score ≥ 7 points (OR 5.08, 95% CI 1.17–20.0; P = 0.030), and right-sided colectomy (OR 4.67, 95% CI 1.46–15.0; P = 0.009) as independent risk factors for RSRC. Postoperative hospital stays were significantly longer for patients with RSRC than for those without RSRC (22 days vs. 11 days; P < 0.001). Conclusion: Short-term outcomes of LSR for patients with sCRLM were acceptable in an experienced center. RSRC was the most common complication, and high-difficulty hepatectomy, right-sided colectomy, and ASA classification ≥ 3 were independent risk factors for RSRC. [ABSTRACT FROM AUTHOR]

The usefulness of the derived neutrophil-to-lymphocyte ratio (dNLR) and its dynamics before/after durvalumab consolidation therapy to predict safety or efficacy remains unclear. We retrospectively reviewed patients with locally advanced non-small cell lung cancer treated with durvalumab consolidation therapy after chemoradiotherapy (D group) or chemoradiotherapy alone (non-D group) at multiple institutions. We investigated the association between dNLR, or its dynamics, and pneumonitis, checkpoint inhibitor-related pneumonitis (CIP), irAEs, and efficacy. Ninety-eight and fifty-six patients were enrolled in the D and non-D groups, respectively. The dNLR at baseline was significantly lower in patients who experienced irAEs or CIP than in those who did not. The low dNLR group, 28 days following durvalumab consolidation therapy (dNLR28 ≤ 3), demonstrated longer progression-free survival (PFS) and overall survival (OS) than the high dNLR group (dNLR28 > 3) (PFS, hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.22–0.88, p = 0.020; OS, HR 0.39, 95% CI 0.16–0.94, p = 0.037). Among patients with high dNLR at baseline (dNLR > 3), the dNLR28 ≤ 3 group showed longer PFS than the dNLR28 > 3 group (p = 0.010). The dNLR is a predictive factor for irAEs and CIP in patients receiving durvalumab consolidation therapy. The dNLR at 28 days after durvalumab consolidation therapy and its dynamics predict favorable outcomes. [ABSTRACT FROM AUTHOR]

Speech-language therapists/pathologists (SLT/Ps) are key professionals in the management and treatment of primary progressive aphasia (PPA), however, there are gaps in education and training within the discipline, with implications for skills, confidence, and clinical decision-making. This survey aimed to explore the areas of need amongst SLT/Ps working with people living with PPA (PwPPA) internationally to upskill the current and future workforce working with progressive communication disorders. One hundred eighty-six SLT/Ps from 27 countries who work with PwPPA participated in an anonymous online survey about their educational and clinical experiences, clinical decision-making, and self-reported areas of need when working with this population. Best practice principles for SLT/Ps working with PwPPA were used to frame the latter two sections of this survey. Only 40.7% of respondents indicated that their university education prepared them for their current work with PwPPA. Competency areas of "knowing people deeply," "practical issues," "connectedness," and "preventing disasters" were identified as the basic areas of priority and need. Respondents identified instructional online courses (92.5%), sample tools and activities for interventions (64.8%), and concrete training on providing care for advanced stages and end of life (58.3%) as central areas of need in their current work. This is the first international survey to comprehensively explore the perspectives of SLT/Ps working with PwPPA. Based on survey outcomes, there is a pressing need to enhance current educational and ongoing training opportunities to better promote the well-being of PwPPA and their families, and to ensure appropriate preparation of the current and future SLT/P workforce. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effect of magnification error and axial length (AL) on circumpapillary capillary density (cpCD) and circumpapillary retinal nerve fiber layer thickness (cpRNFLT) in healthy eyes. Seventy-two healthy eyes of 72 subjects with AL 24.7 ± 1.5 mm (range: 20.9–28.0 mm) were enrolled in this retrospective cross-sectional study and underwent optical coherence tomography angiography scanning. Magnification corrected measurement areas were obtained using AL upon which corrected cpCD, cpRNFLT values were determined. Relationships between AL and the percentage difference between corrected and uncorrected values (ΔcpCD, ΔcpRNFLT) as well as the effect of AL on magnification corrected cpCD, cpRNFLT were evaluated. ΔcpCD significantly increased with AL in the global, inferior nasal and superior nasal sectors (all p < 0.001). ΔcpRNFLT significantly increased with AL in global and all sectors (all p < 0.001) and the correlations were significantly stronger than that of ΔcpCD-AL in all sectors (all p < 0.001). Corrected cpCD did not associate with AL while corrected cpRNFLT demonstrated a significant positive association with AL in the global (p = 0.005) and temporal sector (p < 0.001). Magnification error led to a significant underestimation of cpCD in eyes with longer AL although its underestimation and the effect of AL was smaller in comparison to that of cpRNFLT. [ABSTRACT FROM AUTHOR]

Interconnectors play a crucial role in electric power systems. They contribute to balancing demand and supply in real-time, guaranteeing efficient dispatch in wide geographic regions, and increasing competition by creating large markets. However, interconnector capacity is a scarce resource because vertically integrated utilities were required to have generating capacity enough to supply most customers within their operating region under a regulated monopoly. Hence, identifying the efficient allocation method is essential, particularly after recent electricity market restructuring. This study evaluates the competitive effect of the implicit auction on the interconnector transmission capacity. The implicit auction allocates all the interconnector capacity simultaneously with electric energy in the day-ahead market. This method prevents market participants from strategically withholding the physical interconnector capacity ex ante to exercise market power, as allowed under the first come, first served rule. This study empirically shows how the capacity was withheld from the day-ahead market under the first come, first served rule using detailed reservation data. Next, I show that the implicit auction increases interconnector capacity available at the day-ahead market and trade volume. I use machine-learning methods, such as random forest and deep neural networks, to predict the counterfactual market outcomes without implicit auction. I find that the gain from trade under the implicit auction is more than US$55 million per year in Japan, which is more than 100 times the implementation cost of the implicit auction. [ABSTRACT FROM AUTHOR]

Purpose: Saliva is often used as a tool for identifying systemic diseases because of the noninvasive nature of its collection. Moreover, salivary metabolites can be potential predictive factors for postoperative survival. We conducted the present study to establish whether salivary metabolites can function as predictive biomarkers for lung surgery complications. Methods: Unstimulated salivary samples were collected from 412 patients before lung surgery. Salivary metabolites were analyzed comprehensively by capillary electrophoresis mass spectrometry. Clinical data with the discriminatory ability of biomarkers were assessed to predict lung surgery complications using multivariate logistic regression analysis. The primary endpoint was the risk factors for postoperative complications of Clavien–Dindo grade ≥ III. Results: Postoperative complications of Clavien–Dindo grade ≥ III developed in 36 patients (8.7%). There was no postoperative 30-day mortality. Male sex (odds ratio [OR], 3.852; 95% confidence interval CI 1.455–10.199; p = 0.007) and salivary gamma-butyrobetaine (OR, 0.809; 95% CI 0.694–0.943; p = 0.007) were identified as significant risk factors for postoperative complications of Clavien–Dindo grade ≥ III. Conclusion: Salivary metabolites are potential noninvasive biomarkers for predicting postoperative complications of lung surgery. [ABSTRACT FROM AUTHOR]

A 53-year-old woman with a history of recurrent right lower quadrant pain presented with slightly bloody stools in April 2023. She was initially diagnosed with acute diverticulitis using an abdominal computed tomography (CT) scan and was treated conservatively. On the second day, however, she reported significant hematochezia. A subsequent contrast-enhanced CT scan revealed an extravasation in the ascending colon, which was promptly managed with colonoscopy. Despite initial hemostasis, she experienced recurrent bleeding. Another contrast-enhanced CT scan revealed a pseudoaneurysm with ongoing extravasation in the same area. Angiography confirmed a pseudoaneurysm in a branch of the ileocolic artery, which was successfully treated by embolization. She was discharged after an 18 day hospital stay. This case highlights a pseudoaneurysm caused by diverticulitis. [ABSTRACT FROM AUTHOR]

Here, we report a rare case of a depressed lesion exhibiting both tubular differentiated adenocarcinomatous (TDA) and intraepithelial foveolar neoplasia (IFN) components (with the histological appearance of foveolar hyperplasia due to low-grade atypia). Histologically, the TDA surrounded the IFN, suggesting that the TDA may have originated from the IFN. Therefore, we examined molecular alterations in the TDA and IFN components separately. MUC5AC and MUC6 expression was observed immunohistochemically in both components. p53 expression was wild type in both components, suggesting no mutation of TP53. We investigated allelic imbalances at multiple loci (1p, 3p, 4p, 5q, 8q, 9p, 13q, TP53, 18q, and 22q), mutations (KRAS, BRAF, and GNAS), and DNA methylation and microsatellite status in both components using PCR-based analyses. Although multiple allelic imbalances were common to both components, allelic imbalances at 3p and TP53 were found only in the TDA component. No mutations were found, and DNA methylation status was low epigenotype for both components. Ultimately, this tumor was considered microsatellite stable. Considering the origin of TDA, which is frequently encountered in routine practice, IFN may develop into TDA. [ABSTRACT FROM AUTHOR]

An accurate understanding of the current and future water cycle over the Third Pole is of great societal importance, given the role this region plays as a water tower for densely populated areas downstream. An emerging and promising approach for skillful climate assessments over regions of complex terrain is kilometer-scale climate modeling. As a foundational step towards such simulations over the Third Pole, we present a multi-model and multi-physics ensemble of kilometer-scale regional simulations for the hydrological year of October 2019 to September 2020. The ensemble consists of 13 simulations performed by an international consortium of 10 research groups, configured with a horizontal grid spacing ranging from 2.2 to 4 km covering all of the Third Pole region. These simulations are driven by ERA5 and are part of a Coordinated Regional Climate Downscaling EXperiment Flagship Pilot Study on Convection-Permitting Third Pole. The simulations are compared against available gridded and in-situ observations and remote-sensing data, to assess the performance and spread of the model ensemble compared to the driving reanalysis during the cold and warm seasons. Although ensemble evaluation is hindered by large differences between the gridded precipitation datasets used as a reference over this region, we show that the ensemble improves on many warm-season precipitation metrics compared with ERA5, including most wet-day and hour statistics, and also adds value in the representation of wet spells in both seasons. As such, the ensemble will provide an invaluable resource for future improvements in the process understanding of the hydroclimate of this remote but important region. [ABSTRACT FROM AUTHOR]

Self-amplifying RNAs (saRNAs) are versatile vaccine platforms that take advantage of a viral RNA-dependent RNA polymerase (RdRp) to amplify the messenger RNA (mRNA) of an antigen of interest encoded within the backbone of the viral genome once inside the target cell. In recent years, more saRNA vaccines have been clinically tested with the hope of reducing the vaccination dose compared to the conventional mRNA approach. The use of N1-methyl-pseudouridine (1mΨ), which enhances RNA stability and reduces the innate immune response triggered by RNAs, is among the improvements included in the current mRNA vaccines. In the present study, we evaluated the effects of this modified nucleoside on various saRNA platforms based on different viruses. The results showed that different stages of the replication process were affected depending on the backbone virus. For TNCL, an insect virus of the Alphanodavirus genus, replication was impaired by poor recognition of viral RNA by RdRp. In contrast, the translation step was severely abrogated in coxsackievirus B3 (CVB3), a member of the Picornaviridae family. Finally, the effects of 1mΨ on Semliki forest virus (SFV), were not detrimental in in vitro studies, but no advantages were observed when immunogenicity was tested in vivo. [ABSTRACT FROM AUTHOR]

Background: Chemokine signaling within the tumor microenvironment can promote tumor progression. Although CCR1 and CXCR2 on myeloid cells could be involved in tumor progression, it remains elusive what effect would be observed if both of those are blocked. Methods: We employed two syngeneic colorectal cancer mouse models: a transplanted tumor model and a liver metastasis model. We generated double-knockout mice for CCR1 and CXCR2, and performed bone marrow (BM) transfer experiments in which sub-lethally irradiated wild-type mice were reconstituted with BM from either wild-type, Ccr1−/−, Cxcr2−/− or Ccr1−/−Cxcr2−/− mice. Results: Myeloid cells that express MMP2, MMP9 and VEGF were accumulated around both types of tumors through CCR1- and CXCR2-mediated pathways. Mice reconstituted with Ccr1−/−Cxcr2−/− BM exhibited the strongest suppression of tumor growth and liver metastasis compared with other three groups. Depletion of CCR1+CXCR2+ myeloid cells led to a higher frequency of CD8+ T cells, whereas the numbers of Ly6G+ neutrophils, FOXP3+ Treg cells and CD31+ endothelial cells were significantly decreased. Furthermore, treatment with a neutralizing anti-CCR1 mAb to mice reconstituted with Cxcr2−/− BM significantly suppressed tumor growth and liver metastasis. Conclusion: Dual blockade of CCR1 and CXCR2 pathways in myeloid cells could be an effective therapy against colorectal cancer. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the presence of adipose tissue surrounding the flexor hallucis longus (FHL) tendon through gross dissection and magnetic resonance imaging (MRI). Grossly, we observed the FHL tendon and surrounding tissues in nine cadavers. Using MRI, we quantitatively evaluated each tissue from the horizontal plane in 40 healthy ankles. Macroscopic autopsy revealed the presence of adipose tissue behind the ankle joint between the FHL and fibula, and horizontal cross-sections showed an oval-shaped adipose tissue surrounding the tendon. The cross-sectional area on MRI was 14.4 mm2 (11.7–16.7) for the FHL tendon and 120.5 mm2 (100.3–149.4) for the adipose tissue. Additionally, the volume of the adipose tissue was 963.3 mm3 (896.2–1115.6). There is an adipose tissue around FHL tendon and maybe this close anatomical relationship might influence the function of the tendon and be involved in its pathologies. [ABSTRACT FROM AUTHOR]

The nurse effect is a positive interaction in which a nurse plant improves the abiotic environment for another species (beneficiary plant) and facilitates its establishment. The evergreen shrub Vaccinium vitis-idaea (a beneficiary plant) grows mainly under the dwarf shrub Pinus pumila (a nurse plant) in the alpine regions of central Japan. However, whether V. vitis-idaea shrubs under various P. pumila shrubs spread through clonal growth and/or seeds remains unclear. We investigated the clonal structure of V. vitis-idaea under the nurse plant P. pumila in Japanese alpine regions. MIG-seq analysis was conducted to clarify the clonal diversity of V. vitis-idaea in isolated and patchy P. pumila plots on a ridge (PATs), and in a plot covered by dense P. pumila on a slope adjacent to the ridge (MAT) on Mt. Norikura, Japan. We detected 28 multilocus genotypes in 319 ramets of V. vitis-idaea across 11 PATs and MAT. Three genets expanded to more than 10 m in the MAT. Some genets were shared among neighboring PATs or among PATs and MAT. These findings suggest that the clonal growth of V. vitis-idaea plays an important role in the sustainability of populations. The clonal diversity of V. vitis-idaea was positively related with the spatial size of PATs and was higher in MAT than in PATs at a small scale. Therefore, the spatial spread of the nurse plant P. pumila might facilitate the nurse effect on the genetic diversity of beneficiary plants, leading to the sustainability of beneficiary populations. [ABSTRACT FROM AUTHOR]

Background: Neoplasms derived from remnant appendix are rarely described, with most cases arising from the appendiceal "stump". Here, we present two surgical cases of appendiceal neoplasms derived from appendiceal "tip" remnants. Case presentation: The first patient was a 71-year-old man who had undergone laparoscopic appendectomy for acute appendicitis 12 years prior. During appendectomy, the appendiceal root was ligated, but the appendix was not completely removed due to severe inflammation. At the most recent presentation, computed tomography (CT) was performed to examine choledocholithiasis, which incidentally revealed a cystic lesion of approximately 90 mm adjacent to the cecum. A retrospective review revealed that the cystic lesion had increased in size over time, and laparoscopic ileocecal resection was performed. Pathology revealed no continuity from the appendiceal orifice to the cyst, and a diagnosis of low-grade appendiceal mucinous neoplasm (LAMN) was made from the appendiceal tip remnant. The patient was discharged without complications. The second patient was a 65-year-old man who had undergone surgery for peritonitis due to severe appendicitis 21 years prior. During this operation, the appendix could not be clearly identified due to severe inflammation; consequently, cecal resection was performed. He was referred to our department with a chief complaint of general fatigue and loss of appetite and a cystic lesion of approximately 85 mm close to the cecum that had increased over time. CT showed irregular wall thickening, and malignancy could not be ruled out; therefore, laparoscopic ileocecal resection with D3 lymph node dissection was performed. The pathological diagnosis revealed mucinous adenocarcinoma (TXN0M0) arising from the remnant appendiceal tip. The patient is undergoing follow-up without postoperative adjuvant chemotherapy, with no evidence of pseudomyxoma peritonei or cancer recurrence for 32 months postoperatively. Conclusions: If appendicitis-associated inflammation is sufficiently severe that accurate identification of the appendix is difficult, it may remain on the apical side of the appendix, even if the root of the appendix is ligated and removed. If the appendectomy is terminated incompletely, it is necessary to check for the presence of a residual appendix postoperatively and provide appropriate follow-up. [ABSTRACT FROM AUTHOR]

To achieve the goal of a 50% reduction of CO2 emission in the maritime industry by 2050, different systems and solutions were proposed by researchers. Rigid wind sails, rotor sails, suction wings, and kites were developed to contribute to cleaner and environment-friendly transportation by reducing total fuel and energy consumption. In the present study, a ship dynamics model of KVLCC2 consisting of hull, rudder, propeller, and sailing system was built considering the effects of wind and wave. Firstly, the amount of energy consumption reduction of both systems was examined under different wind directions and wind speeds. It was found that a single sailing system can reduce total energy consumption by up to 10%. Then, the effects of the ship speed, the position of the sailing system, and the number of sails on the reduction of energy consumption were examined. It was found that the amount of overall energy reduction reaches around 23% and 16% when the number of sails was increased to 10 rigid wind sails and 10 rotor sails, respectively. The effects of waves were also investigated, and it was revealed that wave forces decrease the percent energy reduction more when environmental conditions become more severe, starting from the Beaufort scale of 7. [ABSTRACT FROM AUTHOR]

Catalytic hydrogenolysis systems of C-O bonds in furan ring, tetrahydrofuran ring and tetrahydropyran ring in biomass-derived cyclic compounds are reviewed. Furfural or its hydrogenation products (furfuryl alcohol and tetrahydrofurfuryl alcohol) have been frequently used as substrates for this type of reactions. Ring-opening of furfuryl alcohol over metal catalysts combined with basic components gives a mixture of 1,2-pentanediol, 1,5-pentanediol and other by-products. The selectivity much depends on catalysts and reaction conditions, and good 1,2-pentanediol selectivity can be obtained. For 1,5-pentanediol synthesis, more selective approaches have been reported such as Cu-zeolite catalysts for furfuryl alcohol hydrogenolysis in flow reactor and M-M'Ox-type (M: noble metal; M': transition metal) supported catalysts or Ni-LnOx (Ln: rare earth element) catalysts for tetrahydrofurfuryl alcohol hydrogenolysis. The metal catalysts and M-M'Ox-type catalysts can be applied to ring-opening hydrogenolysis of other furan- and tetrahydrofuran-based compounds, respectively. Among the products of ring-opening hydrogenolysis of biomass-derived compounds, 1,5-pentanediol seems to be the most important because of the potential use as a monomer. The recent progress and reported properties of polymers using 1,5-pentanediol as a monomer are also summarized. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the incidence and clinical impact of occult bacteremia in liver transplantation (LT). Methods: This prospective observational study involved a fixed-point observation for up to 2 weeks after living donor LT in 20 recipients, with 20 donors as comparison subjects. Bacteria in the blood samples were detected using the ribosomal RNA-targeted reverse-transcription quantitative polymerase chain reaction method. To identify the causality with the gut microbiota (GM), fecal samples were collected and analyzed simultaneously. Results: Occult bacteremia was identified in four recipients (20%) and three donors (15%) before the operation, and in seven recipients (35%) and five donors (25%) after the operation. Clostridium leptum subgroup, Prevotella, Colinesella, Enterobacteriaceae, and Streptococcus were the main pathogens responsible. Although it did not negatively affect the donor post-hepatectomy outcomes, the recipients with occult bacteremia had a higher rate of infectious complications post-LT. The GM analyses showed fewer post-LT predominant obligate anaerobes in both the recipients and donors with occult bacteremia. Conclusions: Occult bacteremia is a common condition that occurs in both donors and recipients. While occult bacteremia generally remains subclinical in the healthy population, there is potential risk of the development of an apparent post-LT infection in recipients who are highly immunosuppressed. [ABSTRACT FROM AUTHOR]

Background: High skeletal muscle mass might be a prognostic factor for patients with pancreatic ductal adenocarcinoma (PDAC); however, the underlying reason is unclear. We hypothesized that myokines, which are cytokines secreted by the skeletal muscle, function as suppressors of PDAC. We specifically examined irisin, a myokine, which plays a critical role in the modulation of metabolism, to clarify the anticancer mechanisms. Methods: First, the effect of the conditioned medium (CM) from skeletal muscle cells and from irisin-knockdown skeletal muscle cells on PDAC cell lines was evaluated. We then investigated the effects and anticancer mechanism of irisin in PDAC cells, and evaluated the anticancer effect of recombinant irisin in a PDAC xenograft mouse model. Finally, patients undergoing pancreatic resection for PDAC were divided into two groups based on their serum irisin level, and the long-term outcomes were evaluated. Results: The CM enhanced gemcitabine sensitivity by inducing apoptosis and decreasing cell migration by inhibiting epithelial–mesenchymal transition (EMT) in PDAC cell lines. The CM derived from irisin-knockdown skeletal muscle cells did not affect the PDAC cell lines. The addition of recombinant irisin to PDAC cell lines facilitated sensitivity to gemcitabine by inhibiting the mitogen-activated protein kinase (MAPK) pathway, and decreased migration by inhibiting EMT via the transforming growth factor-β/SMAD pathway. Xenografts injected with gemcitabine and recombinant irisin grew slower than the xenografts injected with gemcitabine alone. The overall survival was prolonged in the high-irisin group compared with that in the low-irisin group. Conclusions: Skeletal muscle-derived irisin may affect PDAC by enhancing its sensitivity to gemcitabine and suppressing EMT. [ABSTRACT FROM AUTHOR]

Abstract Healthcare workers (HCWs) treating and caring for patients with emerging infectious diseases often experience psychological distress. However, the psychological impact and behavior change of the coronavirus disease 2019 (COVID-19) pandemic among HCWs are still unknown. This study aimed to investigate the worries and concerns of HCWs regarding the COVID-19 pandemic. In this cross-sectional survey, a web-based questionnaire was distributed among HCWs working in hospitals or clinics across Japanese medical facilities from April 20 to May 1, 2020. The questionnaire comprised items on demographics, worries and concerns, perceptions regarding the sufficiency of information, and behavioral changes pertaining to the COVID-19 pandemic. A total of 4386 HCWs completed the survey; 1648 (64.7%) were aged 30–39 years, 2379 (54.2%) were male, and 782 (18.1%) were frontline HCWs, directly caring for patients with COVID-19 on a daily basis. 3500 HCWs (79.8%) indicated that they were seriously worried about the pandemic. The most frequent concern was the consequence of becoming infected on their family, work, and society (87.4%). Additionally, the majority (55.5%) had restricted social contact and almost all HCWs endorsed a shortage in personal protective equipment (median, 8/9 (interquartile range; 7–9) on a Likert scale). There was no significant difference in the degree of worry between frontline and non-frontline HCWs (8/9 (7–9) vs. 8/9 (7–9), p = 0.25). Frontline HCWs, compared to non-frontline HCWs, were more likely to have the need to avoid contact with families and friends (24.8% vs. 17.8%, p

Resolving inflammation is thought to return the affected tissue back to homoeostasis but recent evidence supports a non-linear model of resolution involving a phase of prolonged immune activity. Here we show that within days following resolution of Streptococcus pneumoniae-triggered lung inflammation, there is an influx of antigen specific lymphocytes with a memory and tissue-resident phenotype as well as macrophages bearing alveolar or interstitial phenotype. The transcriptome of these macrophages shows enrichment of genes associated with prostaglandin biosynthesis and genes that drive T cell chemotaxis and differentiation. Therapeutic depletion of post-resolution macrophages, inhibition of prostaglandin E2 (PGE2) synthesis or treatment with an EP4 antagonist, MF498, reduce numbers of lung CD4+/CD44+/CD62L+ and CD4+/CD44+/CD62L-/CD27+ T cells as well as their expression of the α-integrin, CD103. The T cells fail to reappear and reactivate upon secondary challenge for up to six weeks following primary infection. Concomitantly, EP4 antagonism through MF498 causes accumulation of lung macrophages and marked tissue fibrosis. Our study thus shows that PGE2 signalling, predominantly via EP4, plays an important role during the second wave of immune activity following resolution of inflammation. This secondary immune activation drives local tissue-resident T cell development while limiting tissue injury The post-resolution phase of inflammation is not simply a linear path towards cessation of immune response but rather a regulated process involving fluctuating immune activity. Here authors show a pivotal role for post-resolution macrophages in driving a wave of T cell recruitment and activation via prostaglandin E2 and α-integrin signalling during the resolution phase of murine pneumococcal pneumonia. [ABSTRACT FROM AUTHOR]

Influence of land-surface memory effects over the Tibetan Plateau on the Asian summer monsoon has long been studied, but not quantified because of the difficulty of extracting only these effects from observational data. This study examines the impact of spring land-surface conditions, including surface air temperature (SAT) and snow cover, over the Tibetan Plateau and its surrounding regions on the early stage of the Asian summer monsoon using large-ensemble experiments produced by an atmospheric global climate model (AGCM). The results show that the above-normal SAT over and around the Tibetan Plateau in May can enhance June monsoon circulation without the sea surface temperature (SST) forcing. The physical mechanism behind this involves warmed surface air over the plateau enhancing the north–south SAT gradient, leading to strengthening the Asian summer monsoon circulation and precipitation. Inter-ensemble correlation analysis indicated that SAT warming over the plateau is clearly associated with upper-tropospheric anti-cyclonic circulation anomalies in May. Also, although winter land-surface signals do not persist until late spring, SAT anomalies in March tend to persist until May, explaining 10–20% of the total SAT variance in May. Interestingly, the spring SAT impacts on June monsoon circulations vary interannually, indicating that the contribution of the land–atmosphere (L–A) coupling process to interannual monsoon variability differs from year to year. Active L–A coupling years tend to coincide with cooler SSTs with anomalous low-level divergence and upper-level convergence over and around the Maritime continent, implying that SST forcing is associated with the L–A coupling strength. Specifically, in May of the developing stage of monsoon circulation, the weak Walker circulation over the equatorial and northern Indian Ocean and undeveloped monsoon circulation are suitable for the L–A coupling to influence the development of the monsoon circulation effectively. However, the well-known oceanic events, such as El Ni n ~ o, are found to be less connected with the interannual L–A coupling variations. [ABSTRACT FROM AUTHOR]

McKibben pneumatic actuators (MPAs) are soft actuators that exert tension by applying compressed air to expand a rubber tube. Although electro-pneumatic regulators can control air pressure, most are large and expensive. This study utilizes a dynamic quantizer to control the MPA with a small solenoid valve that can only open and close the valve instead of an electro-pneumatic regulator. A dynamic quantizer is one of the quantizers that converts continuous signals to discrete signals. Our previous study confirmed that tension control of MPA under isometric conditions could be realized using a dynamic quantizer. However, it is often necessary to control the length of the MPA as well as the tension of the MPA. This study implements a dynamic quantizer to control the length of the MPA with a small solenoid valve. Numerical simulations and experimental tests verify the effectiveness of the proposed method. The results of the numerical simulations and experimental tests confirmed that the length of the MPA can be controlled using the dynamic quantizer. [ABSTRACT FROM AUTHOR]

Trace elements are minerals that are present in very low concentrations in the human body and yet are crucial for a wide range of physiological functions. Zinc, the second most abundant trace element, is obtained primarily from the diet. After being taken up in the intestine, zinc is distributed to various target organs, where it plays key roles in processes such as immunity, protein folding, apoptosis, and antioxidant activity. Given the important role of zinc in a wide range of enzymatic reactions and physiological processes, zinc deficiency has been identified in a variety of diseases, notably cancer. In recent years, multiple meta-analyses and reviews looking at zinc levels in individual cancer types have been published, as have a plethora of primary studies demonstrating a link between low zinc levels and specific types of cancer. In this review, we summarize recent evidence implicating low zinc concentrations in serum or tissues as a characteristic in a wide range of cancers. We also discuss preliminary findings indicating that zinc level measurement could ultimately become a useful clinical tool for cancer diagnosis and predicting outcomes in patients with cancer. Finally, we suggest future directions for further elucidating the role of zinc deficiency in cancer development and progression. [ABSTRACT FROM AUTHOR]

Background: APC and MUTYH are both well-known colorectal polyposis causative genes. However, 30–50% of colorectal adenomatous polyposis cases are classified as colonic adenomatous polyposis of unknown etiology and lack identifiable pathogenic variants. Although guidelines recommend total proctocolectomy for colonic adenomatous polyposis of unknown etiology with over 100 adenomas, evidence is lacking. This study presents a unique case of localized colonic adenomatous polyposis of unknown etiology with multiple adenocarcinomas, treated with hemicolectomy and regional lymph node dissection. Case presentation: The patient was a 72-year-old woman whose colonoscopy revealed numerous polyps and two adenocarcinomas localized in the right side of the colon, with no lesions in the left side. The patient had no family history of polyposis or colorectal cancer. No extracolonic lesions, enlarged lymph nodes, or distant metastases were found. Considering the patient's age and lesion localization, laparoscopic right hemicolectomy with regional lymph node dissection was performed. Histopathological diagnosis revealed three adenocarcinoma lesions with no lymph node metastasis. The most advanced pathological stage was T2N0M0 Stage I (UICC 8th edition). The patient was alive 5 years postoperatively, without recurrence of cancer or polyposis in the remaining colon and rectum. To diagnose hereditary colorectal cancer/polyposis, a germline multigene panel testing for APC, EPCAM, MBD4, MLH1, MLH3, MSH2, MSH3, MSH6, MUTYH, NTHL1, PMS2, POLD1, POLE, and TP53 was performed using DNA extracted from blood samples: however, no pathogenic variant was detected. Therefore, the patient was diagnosed with colonic adenomatous polyposis of unknown etiology. Conclusions: In this rare case, colonic adenomatous polyposis of unknown etiology, with numerous adenomatous polyps and multiple adenocarcinomas localized in the right side of the colon, was successfully treated with right hemicolectomy and regional lymph node dissection. Despite genetic analysis, no causative germline variants were identified. Segmental colectomy according to the distribution of polyps might be a curative approach. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is an aggressive, immunologically "cold" tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702). Methods: We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on its long-term effects via long-lived memory CD8 + T cells including tissue-resident memory T cells (TRMs) and effector memory T cells (TEMs) differentiated from effector memory precursor cells (TEMps). Results: First, in vitro, OBP-702 significantly induced adenosine triphosphate (ATP), which is important for memory T cell establishment. Next, in vivo, OBP-702 local treatment to murine pancreatic PAN02 tumors increased TEMps via ATP induction from tumors and IL-15Rα induction from macrophages, leading to TRM and TEM induction. Activation of these memory T cells by OBP-702 was also maintained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN + OBP-702 showed significant anti-tumor effects and increased TRMs in OBP-702-uninjected tumors. Finally, in a neoadjuvant model, in which PAN02 cells were re-inoculated after resection of treated-PAN02 tumors, GN + OBP-702 provided long-term anti-tumor effects even after tumor resection. Conclusion: OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer. [ABSTRACT FROM AUTHOR]

The motor neuroscience literature suggests that the central nervous system may encode some motor commands in terms of velocity. In this work, we tackle the question: what consequences would velocity commands produce at the behavioral level? Considering the ubiquitous presence of noise in the neuromusculoskeletal system, we predict that velocity commands affected by stationary noise would produce "random walks", also known as Brownian processes, in position. Brownian motions are distinctively characterized by a linearly growing variance and a power spectral density that declines in inverse proportion to frequency. This work first shows that these Brownian processes are indeed observed in unbounded motion tasks e.g., rotating a crank. We further predict that such growing variance would still be present, but bounded, in tasks requiring a constant posture e.g., maintaining a static hand position or quietly standing. This hypothesis was also confirmed by experimental observations. A series of descriptive models are investigated to justify the observed behavior. Interestingly, one of the models capable of accounting for all the experimental results must feature forward-path velocity commands corrupted by stationary noise. The results of this work provide behavioral support for the hypothesis that humans plan the motion components of their actions in terms of velocity. [ABSTRACT FROM AUTHOR]

Patients with advanced cancer are frequently burdened with a severe sensation of fatigue called cancer-related fatigue (CRF). CRF is induced at various stages and treatments, such as cachexia and chemotherapy, and reduces the overall survival of patients. Objective and quantitative assessment of CRF could contribute to the diagnosis and prediction of treatment efficacy. However, such studies have not been intensively performed, particularly regarding metabolic profiles. Here, we conducted plasma metabolomics of 15 patients with urological cancer. The patients with and without fatigue, including those with cachexia or chemotherapy-induced fatigue, were compared. Significantly lower concentrations of valine and tryptophan were observed in fatigued patients than in non-fatigued patients. In addition, significantly higher concentrations of polyamine pathway metabolites were observed in patients with fatigue and cachexia than in those without cachexia. Patients with exacerbated fatigue due to chemotherapy showed significantly decreased cysteine and methionine metabolism before chemotherapy compared with those without fatigue exacerbation. These findings suggest that plasma metabolic profiles could help improve the diagnosis and monitoring of CRF. [ABSTRACT FROM AUTHOR]

Background: Diversity in hemodynamics of adult congenital heart disease necessitates a case-by-case selection of appropriate surgical and anesthetic options. However, previous case reports regarding the management of laparoscopic surgery in adult patients with congenital heart disease are limited. Case presentation: A 72-year-old man who underwent a laparoscopic right colectomy for colon cancer had a residual ventricular septal defect and right ventricular outflow tract obstruction despite post-repair of tetralogy of Fallot. Pulmonary hypertension or right ventricular dysfunction was not observed. The preoperative pulmonary to systemic blood flow ratio (Qp/Qs) was 2.3. After positive pressure ventilation and insufflation, the amount of left-to-right ventricular shunting decreased, and the Qp/Qs approached 1.0, as calculated from pulmonary arterial and systemic arterial blood gas analysis. Conclusions: Laparoscopic surgery might be tolerable in patients with tetralogy of Fallot who have preserved the right ventricular function, left-to-right ventricular shunting, and no high pulmonary vascular resistance. [ABSTRACT FROM AUTHOR]

Dynamical downscaling with a 20 km horizontal resolution was undertaken over East Asia for the period May–August in 1991–2015 using the Weather Research and Forecasting (WRF) model with Grell-3D ensemble cumulus parameterization as a product of the Impact of Initialized Land Temperature and Snowpack on Sub-Seasonal to Seasonal Prediction (LS4P) program. Simulated climatological precipitation biases were investigated over land during June when heavy precipitation occurred. Simulations underestimated precipitation along the Meiyu/Baiu rainband, while overestimating it farther north. Dry and wet biases expanded to south and north of the Yangtze River in China, respectively, marking years with poor precipitation simulations. Model biases in synoptic-scale circulation patterns indicate a weakened clockwise circulation over the western North Pacific in the model due to active convection there, and suppressed northward moisture transport to the Meiyu/Baiu rainband. Moisture convergence was slightly enhanced over central China due to an apparent anticyclonic circulation bias over northern China. In years with large biases, positive feedback between reduced moisture inflow and inactive convection occurred over southern China, while moisture transport to central China intensified on regional scales, with amplification of dry and wet biases over China. The Kain–Fritch scheme was used to test the influence of cumulus parameterization, improving the dry bias over southern China due to the modification of synoptic-scale circulation patterns in the lower troposphere. However, precipitation was further overestimated over central China, with the accuracy of precipitation distribution deteriorating. [ABSTRACT FROM AUTHOR]

Purpose: Chronic lung allograft dysfunction (CLAD) is a known long-term fatal disorder after lung transplantation. In this study, we evaluated the CLAD classification of the International Society for Heart and Lung Transplantation (ISHLT) for living-donor lobar lung transplantation (LDLLT). Methods: We conducted a single-center retrospective review of data from 73 patients who underwent bilateral LDLLT between 1998 and 2019. Factors related to opacity on computed tomography (CT) and restriction on pulmonary function tests (PFTs) were also analyzed. Results: Overall, 26 (36%) patients were diagnosed with CLAD, including restrictive allograft syndrome (RAS), n = 10 (38.5%); bronchiolitis obliterans syndrome (BOS), n = 8 (30.8%); mixed, n = 1 (3.8%); undefined, n = 2 (7.7%); and unclassified, n = 5 (19.2%). The 5-year survival rate after the CLAD onset was 60.7%. The survival of patients with BOS was significantly better than that of patients with RAS (p = 0.012). In particular, patients with restriction on PFT had a significantly worse survival than those without restriction (p = 0.001). Conclusions: CLAD after bilateral LDLLT does not have a major impact on the recipient survival, especially in patients with BOS. Restriction on PFT may predict a particularly poor prognosis in patients with CLAD after bilateral LDLLT. [ABSTRACT FROM AUTHOR]

Progressive multifocal leukoencephalopathy (PML) rarely occurs in patients with systemic lupus erythematosus (SLE). This report presents the case of a patient who developed PML due to SLE-associated multiple factors. A 60-year-old woman diagnosed with SLE undergoing multiple immunosuppressive therapies, including azathioprine, presented with cerebral cortical symptoms, lymphocytopenia, and vitamin B12 deficiency and was subsequently diagnosed with SLE-associated PML. We evaluated the cause and disease activity of PML, focusing on the longitudinal assessment of lymphocytopenia, JC virus (JCV) DNA copy number in the cerebrospinal fluid, and magnetic resonance imaging (MRI) findings. Discontinuing azathioprine and initiating alternative immunosuppressive treatments with intramuscular vitamin B12 injections affected lymphocytopenia and disease management. However, despite recovery from lymphopenia and JCV DNA copy number being low, the large hyperintense and punctate lesions observed on the fluid-attenuated inversion recovery (FLAIR) images exhibited varying behaviors, indicating that the balance between contributing factors for PML may have fluctuated after the initial treatment. Clinicians should be meticulous when assessing the underlying pathology of the multifactorial causes of PML due to SLE. The difference in the transition pattern of these lesions on FLAIR images may be one of the characteristics of MRI findings in PML associated with SLE, reflecting fluctuations in disease activity and the progression stage of PML. [ABSTRACT FROM AUTHOR]