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Purposes: This study explored the association between the nutritional status and survival outcomes after pancreatic cancer surgery and reconsidered surgical indications in octogenarians. Methods: Three hundred and ninety-three consecutive pancreatic cancer patients who underwent resection were analyzed and grouped according to age (< 70 years old; septuagenarians [70–79 years old], and octogenarians [80–89 years old]). The Charlson age comorbidity index and nutritional parameters were recorded. Survival outcomes and their association with nutritional parameters and prognostic factors were examined. Results: The overall survival was worse in the octogenarians than in other patients. The median overall survivals in the < 70 years old group, septuagenarians, and octogenarians were 27.2, 26.4, and 15.3 months, respectively (P = 0.0828). DUPAN-2 ≥ 150 U/mL, borderline resectable/unresectable tumors, blood loss volume ≥ 500 mL, and blood transfusion were predictors of the overall survival among octogenarians. Nutritional parameter values were worse in the octogenarians than in other patients. The octogenarian age group was not an independent predictor of postoperative complications in a univariate analysis. Conclusions: Survival outcomes were poor in octogenarians. However, an age ≥ 80 years old alone should not be considered a contraindication for pancreatic cancer surgery. The maintenance of perioperative nutritional status is an important factor associated with the survival. [ABSTRACT FROM AUTHOR]

The effect of drug-coated balloons (DCB) on hemodialysis (HD) in patients with femoropopliteal (FP) disease remains uncertain. This study aimed to investigate the outcomes of DCB therapy in patients with FP artery disease on HD. A total of 185 patients with FP lesions (140 HD patients) who underwent DCB treatment were included in the study. The incidence of restenosis and target lesion revascularization (TLR) at 12 months were measured. Risk factors for TLR were also investigated. The mean age was 71.7 years, and diabetes was observed in 82.3% of patients. The mean duration of receiving dialysis was 8.8 years. The mean lesion length was 11.0 cm, and approximately half of the lesions were severely calcified. Severe dissection after DCB therapy was observed in 19.5% of patients. During the follow-up period, 74 restenosis, 68 TLRs, 8 major amputations, and 28 deaths were observed. The freedom rates from restenosis and TLR at 12 months were 63.8% and 71.3%, respectively. The freedom rates after low- and high-dose DCB at 12 months were 61.9% and 70.6% for restenosis (P = 0.49) and 66.4% and 79.4% for TLR (P = 0.095), respectively. Independent risk factors for TLR at 12 months of age were diabetes, chronic limb-threatening ischemia, and severe calcification. When patients were divided into four groups according to the number of these three risk factors, the rates of freedom from TLR at 12 months were 100%, 94.8%, 76.7%, and 30.3% in the groups with no risk factors, any one risk factor, any two risk factors, and all risk factors, respectively (P < 0.0001). Clinical outcomes after endovascular therapy in HD patients with FP disease remain unsatisfactory, even if they are treated with DCB. In particular, patients on HD with diabetes, chronic limb-threatening ischemia, and severe calcification have poor outcomes. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe the etiology and clinical course in children with severe thrombocytosis (ST, platelet counts > 900 × 109/L) and extreme thrombocytosis (ET, platelet counts > 1000 × 109/L) in a tertiary pediatric hospital. Patients aged 0–18 years with platelet counts over 900 × 109/L who were admitted to our hospital were analyzed. Thrombocytosis was defined as a platelet count exceeding 450 × 109/L. Thrombosis was diagnosed based on computed tomography scans or ultrasound findings. Potential factors associated with the development of extreme thrombocytosis were identified using logistic regression models. Only one (0.8%) out of the 120 patients identified with ST (n = 61) and ET (n = 59) had primary thrombocytosis. The most common underlying condition was congenital heart disease (26.7%), followed by Kawasaki disease (16.7%). With the exception of the hemoglobin level, no major differences were found for the baseline characteristics between the ST and ET groups. A lower hemoglobin level (< 10.0 g/dL) at the onset of thrombocytosis was identified as a predictor for ET development (adjusted odds ratio 2.73, 95% confidence interval 1.18–6.28). Overall, 56 of 120 (46.7%) patients received aspirin therapy. Venous thrombosis occurred in one (0.8%) patient. Conclusions: We found a low proportion of primary thrombocytosis and a low incidence of thrombosis in children with ST and ET. Our results suggest that pediatric ST and ET may share common characteristics and may have features that are distinct from those in adults. What is Known: • Secondary thrombocytosis is a frequent finding in children. • Adult extreme thrombocytosis has been found to be associated with primary thrombocytosis. What is New: • There were no major differences in the baseline characteristics between children with severe and extreme thrombocytosis. • The incidence of thrombosis was markedly low in both severe and extreme thrombocytosis groups. [ABSTRACT FROM AUTHOR]

Purpose: The C-reactive protein-albumin-lymphocyte (CALLY) index, which simultaneously evaluates the nutritional, immunological, and inflammatory statuses, is a new prognostic biomarker in patients with various cancers; however, no study has reported the clinical significance of the CALLY index in patients with pancreatic cancer. This study aimed to investigate whether the preoperative CALLY index is a prognostic biomarker in patients undergoing surgical resection of pancreatic cancer. Methods: We retrospectively enrolled 461 patients with pancreatic cancer who underwent surgical resection between January 2013 and December 2022. The overall survival (OS) and relapse-free survival (RFS) rates were calculated using the Kaplan–Meier method. Univariate and multivariate analyses were performed using Cox proportional hazards regression models. Results: The optimal cut-off value for the preoperative CALLY index was 1.9. In the low CALLY group, patients were older (p = 0.012), more patients underwent pancreaticoduodenectomy (p = 0.002), the median tumor size was larger (p < 0.001), more patients had pathologically confirmed metastatic lymph nodes (p = 0.015) and worse pathological stage (p = 0.015), and fewer patients received adjuvant chemotherapy (p = 0.003). A low CALLY index was associated with decreased OS (22.1 vs. 37.9 months) and RFS (12.4 vs. 16.4 months). Univariate and multivariate analyses showed that the preoperative CALLY index was an independent prognostic factor for OS (p < 0.001) and RFS (p = 0.045). Conclusion: The preoperative CALLY index is a prognostic biomarker for both OS and RFS in patients undergoing surgery for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Criteria for airflow obstruction (AFO) at one year after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in pulmonary function tests (PFTs) are more stringent than the bronchiolitis obliterans syndrome (BOS) criteria of the National Institutes of Health. This single-center, retrospective cohort study evaluated the clinical impact of the AFO criteria at any time after transplantation. In 132 patients who underwent allo-HSCT from 2006 to 2016, the 2-year cumulative incidence of AFO was 35.0%, and the median time to diagnosis of AFO was 101 days after transplantation (range 35–716 days). Overall chronic graft-versus-host disease (cGVHD) incidence was significantly higher in patients with AFO than in those without AFO (80.4% vs. 47.7%, P < 0.01); notably, 37.0% of patients with AFO developed cGVHD after AFO diagnosis. AFO patients developed BOS with a 5-year cumulative incidence of 49.1% after AFO onset. The 5-year cumulative incidence of non-relapse mortality in the AFO group was higher than that in the non-AFO group (24.7% vs. 7.1%, P < 0.01). These results suggest that closely monitoring PFTs within two years after allo-HSCT, regardless of cGVHD status, is important for early detection of AFO and prevention of progression to BOS. (192words). [ABSTRACT FROM AUTHOR]

Background: Programmed cell death-1 (PD-1) blockade improves survival in patients with advanced esophageal squamous cell carcinoma (ESCC). However, the efficacy of taxanes after exposure to PD-1 blockade remains unclear in patients with advanced ESCC. Methods: We retrospectively analyzed the clinical outcomes of advanced ESCC patients treated with taxanes (paclitaxel or docetaxel) with/without prior exposure to PD-1 blockade (Exposed /Naïve group) at National Cancer Center Hospital from June 2016 to December 2020. Results: Ninety-nine patients (Exposed group, n = 32; Naïve group, n = 67) were included. The objective response rate (ORR) of the Exposed group was significantly higher than that of the Naïve group (37.5% vs. 13.4%, p = 0.009). The median progression-free survival was similar between the Exposed and Naïve groups (3.8 vs. 2.8 months, HR 1.12, 95% CI 0.65–1.86, p = 0.66). PD-1 blockade exposure independently predicated higher ORR to taxanes in multivariate analysis. Grade ≥ 3 adverse events were comparable between the Exposed and Naïve groups (45.8% vs. 40.3%, p = 0.64). Conclusions: Taxanes following PD-1 blockade in advanced ESCC showed a higher ORR but similar PFS compared to taxanes without prior PD-1 exposure. [ABSTRACT FROM AUTHOR]

Biodegradable plastics applied to soil stimulate the production of greenhouse gases and inhibit plant growth under aerobic conditions. This study aimed to examine the effects of biodegradable plastics on paddy rice growth and greenhouse gas emission under flooding conditions in pot experiments and also on greenhouse gas production under flooding conditions in an incubation experiment. Two series of pot experiments were conducted with rice (Oryza sativa). First series as immediate flooded and 2nd series as 2 weeks nonflooding before flooded, and both kept flooded until harvest. The following four kinds of materials were added to the sandy paddy soil, (1) nonwoven fabric sheets made of polylactic acid and polybutylene-succinate, (2) laminate sheets made of polybutylene adipate terephthalate and pulp, (3) cellulose filter paper, and (4) rice straw. Only soil was used as control. Methane (CH4) emission, measured by chamber method followed by gas chromatography, was significantly larger only in the cellulose treatment than the laminate treatment in the immediate flooded series, indicating that biodegradable plastics had no significant impact on CH4 emission from paddy rice soil. Rice growth and yield did not show significant difference among treatments in both series. Incubation experiment showed the largest CH4 production in cellulose-amended soil, followed by straw-amended and laminate amended soils, and least in fabric-amended soil, while CO2 did not show significant differences among treatments. We need further examination with different biodegradable plastics for a longer period that test used in this study. [ABSTRACT FROM AUTHOR]

When laser radiation is skilfully applied, atoms and molecules can be cooled1–3, allowing the precise measurements and control of quantum systems. This is essential for the fundamental studies of physics as well as practical applications such as precision spectroscopy4–7, ultracold gases with quantum statistical properties8–10 and quantum computing. In laser cooling, atoms are slowed to otherwise unattainable velocities through repeated cycles of laser photon absorption and spontaneous emission in random directions. Simple systems can serve as rigorous testing grounds for fundamental physics—one such case is the purely leptonic positronium11,12, an exotic atom comprising an electron and its antiparticle, the positron. Laser cooling of positronium, however, has hitherto remained unrealized. Here we demonstrate the one-dimensional laser cooling of positronium. An innovative laser system emitting a train of broadband pulses with successively increasing central frequencies was used to overcome major challenges posed by the short positronium lifetime and the effects of Doppler broadening and recoil. One-dimensional chirp cooling was used to cool a portion of the dilute positronium gas to a velocity distribution of approximately 1 K in 100 ns. A major advancement in the field of low-temperature fundamental physics of antimatter, this study on a purely leptonic system complements work on antihydrogen13, a hadron-containing exotic atom. The successful application of laser cooling to positronium affords unique opportunities to rigorously test bound-state quantum electrodynamics and to potentially realize Bose–Einstein condensation14–18 in this matter–antimatter system.The one-dimensional laser cooling of positronium enables testing of quantum electrodynamics and could realize Bose–Einstein condensation in positronium. [ABSTRACT FROM AUTHOR]

Scuellaria Root (SR, root of Scutellaria baicalensis), which has potent anti-inflammatory effects, is a component of useful Kampo formulae. Albeit a low frequency, SR induces serious interstitial pneumonia and liver dysfunction. In this study, to control the adverse effects of SR, we investigated the causal constituent responsible for its hepatocytotoxicity and aimed to develop a method to control it. As a result, we revealed that the hepatocytotoxicity of SR was correlated with its baicalin content, a major constituent in SR. It was confirmed by preparing a baicalin-free SR extract, which exhibited reduced hepatocytotoxicity. The addition of baicalin to the baicalin-free SR extract restored the hepatocytotoxicity, indicating that the hepatocytotoxicity of SR is dependent on its baicalin content. Thus, SR extract-induced hepatocytotoxicity can be controlled by regulating its baicalin content. [ABSTRACT FROM AUTHOR]

In the past few decades, the global prevalence of diabetes has provided us with a warning about future chronic complications. Diabetic nephropathy (DN) is the main cause of end-stage kidney disease. Podocytes in the glomerulus play a critical role in regulating glomerular permeability, and podocyte injury is one of the main causes of DN. Extracellular signal-regulated kinase (ERK) is a member of the mitogen-activated protein kinase family that plays critical roles in intracellular signal transduction. In human patients with DN, phosphorylated ERK (pERK), the active form of ERK, is increased in the glomeruli. However, information on the expression of pERK, specifically in podocytes in DN, is limited. Meanwhile, high glucose induces ERK activation in immortalized podocyte cell lines, suggesting the involvement of podocytic ERK in DN. We performed an immunohistochemical study using Wilms' tumor-1 (WT-1) as a podocyte-specific marker to investigate whether podocytic pERK levels are increased in patients with DN. In the glomeruli of the DN group, we observed remarkable co-staining for WT-1 and pERK. In contrast, the glomeruli of the control group contained only a few pERK-positive podocytes. Statistical analyses revealed that, relative to healthy controls, patients with DN showed significantly increased pERK expression levels in cells that were positive for WT-1 (DN: 51.3 ± 13.1% vs. control: 7.3 ± 1.6%, p = 0.0158, t-test, n = 4 for each group). This suggests that ERK activation in podocytes is involved in the pathogenesis of DN. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the feasibility, safety, diagnostic yield, and technical aspects of percutaneous abdominal lavage cytology screening (PACS) in patients with resectable pancreatic cancer. Methods: This single-center, retrospective study included patients with resectable pancreatic cancer who underwent PACS before pancreatectomy between May 2022 and October 2023. The technical success rate, position of the drainage tube, volume of fluid administered, volume of fluid retrieved, fluid retrieval rate, and adverse events were evaluated. The cytological results of PACS were compared with those of surgical peritoneal lavage performed during pancreatectomy. Results: Forty-four patients were enrolled in this study. The technical success rate for PACS was 100%. Drainage tube placement was outside the pouch of Douglas in all patients in the right-sided abdominal approach group (n = 10), whereas the placement was in the pouch of Douglas in all patients in the suprapubic approach group (n = 34). The mean volume of fluid administered, mean volume of fluid retrieved, and fluid retrieval rate were 185.0 ± 22.9 ml vs. 97.1 ± 32.0 ml (p < 0.001), 36.8 ± 25.6 ml vs. 50.5 ± 21.6 ml (p = 0.059), and 19.0 ± 12.4% vs. 54.9 ± 21.9% (p < 0.001) in the right abdominal approach and suprapubic approach groups, respectively. No adverse events were reported. The cytological results were benign in 42 patients; no discrepancy was observed in the results of surgical peritoneal lavage (n = 36). Conclusion: PACS is a feasible and safe procedure that can be performed before pancreatectomy in patients with resectable pancreatic cancer. the suprapubic approach may be ideal and PACS could be a screening method to detect carcinomatous peritonitis [ABSTRACT FROM AUTHOR]

Cervical radiculopathy might affect finger movement and dexterity. Postoperative features and clinical outcomes comparing C8 radiculopathies with other radiculopathies are unknown. This prospective multicenter study analyzed 359 patients undergoing single-level surgery for pure cervical radiculopathy (C5, 48; C6, 132; C7, 149; C8, 30). Background data and pre- and 1-year postoperative neck disability index (NDI) and numerical rating scale (NRS) scores were collected. The C5–7 and C8 radiculopathy groups were compared after propensity score matching, with clinical significance determined by minimal clinically important differences (MCID). Postoperative arm numbness was significantly higher than upper back or neck numbness, and arm pain was reduced the most (3.4 points) after surgery among the C5–8 radiculopathy groups. The C8 radiculopathy group had worse postoperative NDI scores (p = 0.026), upper back pain (p = 0.042), change in arm pain NRS scores (p = 0.021), and upper back numbness (p = 0.028) than the C5–7 group. NDI achieved MCID in both groups, but neck and arm pain NRS did not achieve MCID in the C8 group. In conclusion, although arm numbness persisted, arm pain was relieved after surgery for cervical radiculopathy. Patients with C8 radiculopathy exhibited worse NDI and change in NRS arm pain score than those with C5–7 radiculopathy. [ABSTRACT FROM AUTHOR]

Key summary points: Aim: In this study, the cross-sectional area of the geniohyoid muscle was investigated using ultrasonography to determine the normative and cut-off values. Findings: The cut-off values of the ultrasonographic cross-sectional area of the geniohyoid muscle were found as 172.5 mm2 for women and 194.7 mm2 for men. Message: This cut-off values could help detect loss of swallowing muscle mass and contribute to the diagnosis of sarcopenic dysphagia. Purpose: Determining the strength and area of the swallowing muscles is important in patients with sarcopenic dysphagia. Although the normative data on the strength of the swallowing muscles have been reported, those of the area of the geniohyoid muscle are poorly investigated. We investigated the cross-sectional area of the geniohyoid muscle in Japanese subjects without dysphagia using ultrasonography to determine the normative and cut-off values. Methods: 142 subjects without dysphagia were included. The older group (age ≥ 65 years) included 36 (women 27/men 9) subjects, and the younger group (age ≤ 39 years) included 106 (women 54/men 52) subjects. The cross-sectional area of the geniohyoid muscle was measured by ultrasound. The mean of the younger group-2 standard deviation (SD) was calculated and used as a cut-off value for low swallowing muscle mass. Results: The mean (SD) of the area of the geniohyoid muscle of each group was as follows: older women group 167.2 (32.6) mm2, older men group 193.2 (49.5) mm2, younger women group 247.3 (37.4) mm2, younger men group 313.1 (59.2) mm2. The mean 2SD of the geniohyoid muscle area in the younger women group was 172.5 mm2 and in the younger men group 194.7 mm2. Conclusion: We found that the cut-off value of the ultrasonographic cross-sectional area of the geniohyoid muscle was 172.5 mm2 for women and 194.7 mm2 for men. These values could be used as cut-off values for the mass of the geniohyoid muscle to identify patients with sarcopenic dysphagia. [ABSTRACT FROM AUTHOR]

We report a case of a patient with distal bile duct cancer who presented with ocular pain and eye redness due to a liver abscess. The patient developed a liver abscess while waiting for surgery. Since Klebsiella pneumoniae with high viscosity was identified and imaging studies showed systemic infection, a diagnosis of klebsiella invasive syndrome was made. In addition, infectious intraocular inflammation was also observed at the same time. In addition to antibiotic therapy, vitrectomy and percutaneous transhepatic abscess drainage successfully normalized the inflammatory response and negative blood cultures were obtained. Thirty-four days after the start of treatment, surgery was performed and the postoperative course was uneventful, and the patient was discharged from the hospital on the 39th postoperative day. Forty-six months after that surgery, there has been no evidence of recurrence of cholangiocarcinoma or recurrence of infection, but unfortunately, vision loss in the right eye remains. Some Klebsiella pneumoniae are highly pathogenic and are often reported from Southeast Asia, and ocular pain and hyperemic symptoms are important physical findings. [ABSTRACT FROM AUTHOR]

Background: Letermovir is approved for cytomegalovirus (CMV) prophylaxis in adult allogeneic hematopoietic cell transplantation recipients worldwide and is also approved in the United States for CMV prophylaxis in adult high-risk (D+/R−) kidney transplant recipients (KTRs). The safety and efficacy of letermovir for CMV prophylaxis in adult Japanese KTRs are reported here. Methods: In this Phase 3, single-arm, open-label study, adult Japanese KTRs with CMV serostatuses D+/R−, D+/R+, and D−/R+ received letermovir 480 mg daily orally within 7 days post-transplant through Week 28. Participants were followed through Week 52. The primary objective was to evaluate letermovir safety and tolerability. Efficacy was a secondary objective, measured by CMV disease, CMV disease or infection requiring intervention, and quantifiable CMV DNAemia. All CMV disease cases were confirmed by an independent adjudication committee. Results: Among 22 participants (12 were D+/R−) who received letermovir prophylaxis, 20 (90.9%) experienced ≥ 1 AE through Week 28. Most AEs were mild to moderate in severity; no deaths were reported. During the prophylaxis period through Week 28, one transient case of quantifiable CMV DNAemia was detected, but no CMV disease or infection requiring intervention was reported. Through Week 52, four D+/R− participants met the endpoint of CMV disease or infection requiring intervention, of whom two had committee-confirmed CMV syndrome; all recovered with CMV therapy. A total of 5 participants had quantifiable CMV DNAemia through Week 52. Conclusion: Letermovir was generally well tolerated, and the data support its use for the prevention of CMV disease/infection in adult Japanese KTRs. Trial registration: ClinicalTrials.gov NCT04129398. [ABSTRACT FROM AUTHOR]

Purpose: Spinopelvic sagittal alignment is crucial for assessing balance and determining treatment efficacy in patients with adult spinal deformity (ASD). Only a limited number of reports have addressed spinopelvic parameters and lumbosacral transitional vertebrae (LSTV). Our primary objective was to study spinopelvic sagittal parameter changes in patients with LSTV. A secondary objective was to investigate clinical symptoms and quality of life (QOL) in patients with LSTV. Methods: In this study, we investigated 371 participants who had undergone medical check-ups for the spine. LSTV was evaluated using Castellvi's classification, and patients were divided into LSTV+ (type II-IV, L5 vertebra articulated or fused with the sacrum) and LSTV- groups. After propensity score matching for demographic data, we analyzed spinopelvic parameters, sacroiliac joint degeneration, clinical symptoms, and QOL for these two participant groups. Oswestry Disability Index (ODI) scores and EQ-5D (EuroQol 5 dimensions) indices were compared between the two groups. Results: Forty-four patients each were analyzed in the LSTV + and LSTV- groups. The LSTV + group had significantly greater pelvic incidence (52.1 ± 11.2 vs. 47.8 ± 10.0 degrees, P = 0.031) and shorter pelvic thickness (10.2 ± 0.9 vs. 10.7 ± 0.8 cm, P = 0.018) compared to the LSTV- group. The "Sitting" domain of ODI (1.1 ± 0.9 vs. 0.6 ± 0.7, P = 0.011) and "Pain/Discomfort" domain of EQ-5D (2.0 ± 0.8 vs. 1.6 ± 0.7, P = 0.005) were larger in the LSTV + group. Conclusion: There was a robust association between LSTV and pelvic sagittal parameters. Clinical symptoms also differed between the two groups in some domains. Surgeons should be aware of the relationship between LSTV assessment, radiographic parameters and clinical symptoms. Level of evidence: 3. [ABSTRACT FROM AUTHOR]

This study aimed to develop a quantitative analysis program of blood flow velocity by vessel diameter in neovascular age-related macular degeneration (nAMD) subjects using high-speed swept-source optical coherence tomography angiography. This retrospective, observational, cross-sectional study included 10 eyes of healthy volunteers and 4 eyes of patients with representative nAMD. Novel scan patterns and variable interscan time analysis were utilized to measure the flow parameter, a surrogate marker of blood flow velocity, by vessel diameter within different depths. Detected vessels at superficial and deep as well as outer retinal regions were categorized into three vessel diameters (major vessels (> 40 μm), medium vessels (20–40 μm), and capillaries (< 20 μm)). The flow parameter increased with enlarged vessel diameter in all participants at superficial and deep layer. All nAMD subjects, except for type 3 macular neovascularization (MNV), contained a structure dominated by medium vessels at outer retinal region. The mean flow parameter at outer retinal region was type 1 MNV (1.46 ms−1), type 1 + 2 MNV (0.98 ms−1), and polypoidal choroidal vasculopathy, including branching vascular networks (1.46 ms−1). This program provides the possibility to extract the blood flow information at different depths by vessel diameter types, which is considered to be useful tool for evaluating nAMD pathology and activity. [ABSTRACT FROM AUTHOR]

Background: Most adult cases of intussusception are caused by colorectal cancer, and emergency surgery is performed when symptoms such as abdominal pain and vomiting are present. The patient must customarily undergo both bowel decompression and radical surgery for colorectal cancer at the same time, and laparotomy is generally the procedure of choice. Case presentation: An 86-year-old woman presented to our hospital with diarrhea and bloody stools. Preoperative examination revealed the presence of a cancerous tumor in the advanced part of the transverse colon and bowel intussusception. Radical surgery was successfully performed using the laparoscopic single-port technique through a small incision at the umbilical site to treat intussusception caused by cecum cancer. Conclusions: With only one wound site at the umbilicus, this single-port laparoscopic approach is much less invasive than endoscopic surgery that requires four to five incision wounds to perform the procedure. Furthermore, the patient was discharged without major complications and this surgical technique could be of great benefit if established as a standard procedure in the future. [ABSTRACT FROM AUTHOR]

We established a design method for a Magic-T with a single-layer dielectric/metal structure suitable for both wideband and multi-element applications for millimeter and submillimeter wave imaging observations. The design method was applied to a Magic-T with a coupled-line, stubs, and single-stage impedance transformers in a frequency-scaled model (6–14 GHz) that is relatively easy to demonstrate through manufacturing and evaluation. The major problem is that using the conventional perfect matching condition for a coupled-line alone produces an impractically large width coplanar coupled-line (CPCL) to satisfy the desired bandwidth ratio. In our study, by removing this constraint and optimizing impedances utilizing a circuit simulator with high computation speed, we found a solution with a ∼ 180 μm wide CPCL, which is approximately an order of magnitude smaller than the conventional analytical solution. Furthermore, considering the effect of transition discontinuities in the transmission lines, we optimized the line length and obtained a design solution with return loss < − 20 dB, amplitude imbalance < 0.1 dB, and phase imbalance < 0.5 ∘ from 6.1 to 14.1 GHz. [ABSTRACT FROM AUTHOR]

Purpose: Adult spinal deformity (ASD) is associated with a combination of back and leg pain of various intensities. The objective of the present study was to investigate the diverse reaction of pain profiles following ASD surgery as well as post-operative patient satisfaction. Methods: Multicenter surveillance collected data for patients ≥ 19 years old who underwent primary thoracolumbar fusion surgery at > 5 spinal levels for ASD. Two-step cluster analysis was performed utilizing pre-operative numeric rating scale (NRS) for back and leg pain. Radiologic parameters and patient-reported outcome (PRO) scores were also obtained. One-year post-operative outcomes and satisfaction rates were compared among clusters, and influencing factors were analyzed. Results: Based on cluster analysis, 191 ASD patients were categorized into three groups: ClusterNP, mild pain only (n = 55); ClusterBP, back pain only (n = 68); and ClusterBLP, significant back and leg pain (n = 68). ClusterBLP (mean NRSback 7.6, mean NRSleg 6.9) was the oldest 73.4 years (p < 0.001) and underwent interbody fusion (88%, p < 0.001) and sacral/pelvic fixation (69%, p = 0.001) more commonly than the other groups, for the worst pelvis incidence—lumbar lordosis mismatch (mean 43.7°, p = 0.03) and the greatest sagittal vertical axis (mean 123 mm, p = 0.002). While NRSback, NRSleg and PRO scores were all improved postoperatively in ClustersBP and BLP, ClusterBLP showed the lowest satisfaction rate (80% vs. 80% vs. 63%, p = 0.11), which correlated with post-operative NRSback (rho = −0.357). Conclusions: Cluster analysis revealed three clusters of ASD patients, and the cluster with the worst pain back and leg pain had the most advanced disease and showed the lowest satisfaction rate, affected by postoperative back pain. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic liver resection (LLR) is rapidly gaining popularity; however, its efficacy for nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) (NAFLD-HCC) has been not evaluated. The purpose of this study was to compare short- and long-term outcomes between LLR and open liver resection (OLR) among patients with NAFLD-HCC. Methods: We used a single-institution database to analyze data for patients who underwent LLR or OLR for NAFLD-HCC from January 2007 to December 2022. We performed propensity score-matching analyses to compare overall postoperative complications, major morbidities, duration of surgery, blood loss, transfusion, length of stay, recurrence, and survival between the two groups. Results: Among 210 eligible patients, 46 pairs were created by propensity score matching. Complication rates were 28% for OLR and 11% for LLR (p = 0.036). There were no significant differences in major morbidities (15% vs. 8.7%, p = 0.522) or duration of surgery (199 min vs. 189 min, p = 0.785). LLR was associated with a lower incidence of blood transfusion (22% vs. 4.4%, p = 0.013), less blood loss (415 vs. 54 mL, p < 0.001), and shorter postoperative hospital stay (9 vs. 6 days, p < 0.001). Differences in recurrence-free survival and overall survival between the two groups were not statistically significant (p = 0.222 and 0.301, respectively). Conclusions: LLR was superior to OLR for NAFLD-HCC in terms of overall postoperative complications, blood loss, blood transfusion, and postoperative length of stay. Moreover, recurrence-free survival and overall survival were comparable between LLR and OLR. Although there is a need for careful LLR candidate selection according to tumor size and location, LLR can be regarded as a preferred treatment for NAFLD-HCC over OLR. [ABSTRACT FROM AUTHOR]

Background: A chronic expanding hematoma is an uncommon entity described as an organized blood collection that increases in size after the initial hemorrhagic event without histological neoplastic features. The standard treatment is complete resection. To our knowledge, this is the first report of a chronic expanding hematoma mimicking a pancreatic cystic tumor that has been successfully resected utilizing a laparoscopic approach. Case presentation: We report the case of a 32-year-old man with a 10-cm chronic expanding hematoma that was preoperatively diagnosed as a cystic pancreatic tumor. Dynamic computed tomography revealed a cyst at the inferior part of the uncinate process of the pancreas without contrast enhancement. His blood biochemical data were within normal limits. The operation initially utilized a laparoscopic approach; however, the procedure was converted to hand-assisted laparoscopic surgery due to capsule adherence to surrounding organs and finally, enucleation of the tumor was performed. Pathological findings revealed a chronic expanding hematoma in the retroperitoneal space. Conclusion: Chronic expanding hematoma in the retroperitoneal space is so rare and sometimes adheres to the surrounding tissue. It is difficult to distinguish hematoma attaching pancreas and pancreatic cyst preoperatively. In rare cases such as this, hand-assisted laparoscopic surgery is a feasible, less invasive procedure for facilitating complete resection and preventing recurrence. [ABSTRACT FROM AUTHOR]

Pyroglutamylated RF-amide peptide (QRFP) is a peptide hormone with a C-terminal RF-amide motif. QRFP selectively activates a class A G-protein-coupled receptor (GPCR) GPR103 to exert various physiological functions such as energy metabolism and appetite regulation. Here, we report the cryo-electron microscopy structure of the QRFP26-GPR103-Gq complex at 3.19 Å resolution. QRFP26 adopts an extended structure bearing no secondary structure, with its N-terminal and C-terminal sides recognized by extracellular and transmembrane domains of GPR103 respectively. This movement, reminiscent of class B1 GPCRs except for orientation and structure of the ligand, is critical for the high-affinity binding and receptor specificity of QRFP26. Mutagenesis experiments validate the functional importance of the binding mode of QRFP26 by GPR103. Structural comparisons with closely related receptors, including RY-amide peptide-recognizing GPCRs, revealed conserved and diversified peptide recognition mechanisms, providing profound insights into the biological significance of RF-amide peptides. Collectively, this study not only advances our understanding of GPCR-ligand interactions, but also paves the way for the development of novel therapeutics targeting metabolic and appetite disorders and emergency medical care. GPR103, a GPCR activated by pyroglutamylated RF-amide peptide QRFP, has various physiological functions, such as energy metabolism and appetite regulation. Here, the authors determined the cryoEM structure of the QRFP26- GPR103-Gq complex, revealing its peptide recognition mechanism. [ABSTRACT FROM AUTHOR]

The underlying mechanisms of atherosclerosis, the second leading cause of death among Werner syndrome (WS) patients, are not fully understood. Here, we establish an in vitro co-culture system using macrophages (iMφs), vascular endothelial cells (iVECs), and vascular smooth muscle cells (iVSMCs) derived from induced pluripotent stem cells. In co-culture, WS-iMφs induces endothelial dysfunction in WS-iVECs and characteristics of the synthetic phenotype in WS-iVSMCs. Transcriptomics and open chromatin analysis reveal accelerated activation of type I interferon signaling and reduced chromatin accessibility of several transcriptional binding sites required for cellular homeostasis in WS-iMφs. Furthermore, the H3K9me3 levels show an inverse correlation with retrotransposable elements, and retrotransposable element-derived double-stranded RNA activates the DExH-box helicase 58 (DHX58)-dependent cytoplasmic RNA sensing pathway in WS-iMφs. Conversely, silencing type I interferon signaling in WS-iMφs rescues cell proliferation and suppresses cellular senescence and inflammation. These findings suggest that Mφ-specific inhibition of type I interferon signaling could be targeted to treat atherosclerosis in WS patients. Werner syndrome (WS) is a rare inherited disorder characterized by premature aging and atherosclerosis. Here, the authors mimic atherosclerosis with iPSC-derived macrophages and vascular cells and find that type I IFN signaling triggered by the reactivation of retrotransposable elements in WS macrophages induces vascular dysfunction. [ABSTRACT FROM AUTHOR]

The purposes for performing negative pressure wound therapy (NPWT) in severe burns are diverse, but few reports comprehensively discussing its indications and methods have been published. We included patients with a ≥30% total burn area. There were 4 patients, and a total of 9 NPWT were performed. The therapy sites were the upper extremity (n = 2), the elbow (n = 1), the dorsum of the hand (n = 5), and the knee (n = 1). The purposes of the therapy were bridge-to-skin grafting (n = 5), dressing the artificial dermis (n = 1), therapy for bolstering the autograft (n = 1), bridge-to-flap surgery (n = 1), and covering the flap (n = 1). The devices used were bedside wall suction (n = 5) and dedicated device (n = 3). Therapy was converted to wall aspiration after use of the dedicated device in 1 case. NPWT is an effective option in severe burn treatment. For each purpose, it is necessary to consider the device used, negative pressure setting, starting date, frequency of dressing changes, and period of therapy. NPWT in severe burns also has the advantage of prioritizing life-prolonging treatment. If strict control of negative pressure is required, a dedicated device should be used rather than wall suction. [ABSTRACT FROM AUTHOR]

Childhood maltreatment is reportedly associated with atypical gray matter structures in the primary visual cortex (V1). This study explores the hypothesis that retinal structures, the sensory organs of vision, are associated with brain atypicality and child maltreatment and examines their interrelation. General ophthalmologic examinations, visual cognitive tasks, retinal imaging, and structural magnetic resonance imaging (MRI) were conducted in children and adolescents aged 9–18 years with maltreatment experiences (CM) and typically developing (TD) children. The retinal nerve fiber layer (RNFL), the most superficial of the ten distinct retinal layers, was found to be significantly thinner in both eyes in CM. While whole-brain analysis using Voxel-based morphometry revealed a significantly larger gray matter volume (GMV) in the thalamus in CM, no significant correlation with RNFL thickness was observed. However, based on region-of-interest analysis, a thinner RNFL was associated with a larger GMV in the right V1. Although it cannot be ruled out that this outcome resulted from maltreatment alone, CM demonstrated subclinical structural atypicality in the retina, which may also correlate with the immaturity of V1 development. Examination of retinal thickness offers a novel clinical approach to capturing characteristics associated with childhood maltreatment. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound-guided fine-needle aspiration has become the common procedure for the diagnosis of pancreatic mass, and cytological examination is usually the first approach. Solid pseudopapillary neoplasm (SPN) cytologically represents papillary structures of branching capillaries surrounded by discohesive neoplastic cells. However, it may present various degrees of tissue degeneration, causing diagnostic challenges. Here, we report a 21-year-old female who had a 2-cm-sized mass in the pancreas head. Cytological examination revealed clumps of small round/oval cells that represented microcystic configurations with mucus, mimicking adenoid cystic carcinoma or mucinous adenocarcinoma. Cercariform cells, nuclear grooves/folding, and cytoplasmic vacuoles were not observed. Histopathological examination revealed confluent small glandular structures containing acidic mucus. The tumor cells were positively stained for β-catenin, CD10, and CD56, and negative for chromogranin A and E-cadherin, suggesting SPN, micropseudocystic variant. This variant has been scarcely described, but we should recognize it for accurate cytological triage of pancreatic tumors. [ABSTRACT FROM AUTHOR]

The liver has multiple regeneration modes, including hepatocellular hypertrophy and self-renewal of hepatocytes. When hepatocyte proliferation is impaired, hepatic progenitor cells may proliferate through ductular reaction (DR), differentiate into hepatocytes, and contribute to fibrosis. However, the three-dimensional spatial relationship between DR and regenerating hepatocytes and dynamic changes in DR associated with fibrosis remain poorly understood. Here, we performed three-dimensional (3D) imaging of cleared 42 liver explants with chronic and acute liver diseases and 4 normal livers to visualize DR. In chronic hepatic liver diseases, such as viral hepatitis, steatohepatitis, autoimmune hepatitis, and cryptogenic cirrhosis, the total length and number of branches of DR showed a significant positive correlation. We studied the spatial relationship between DR and GS-expressing cells using glutamine synthetase (GS) and cytokeratin 19 (CK19) as markers of liver regeneration and DR, respectively. The percentage of CK19-positive cells that co-expressed GS was less than 10% in chronic liver diseases. In contrast, nearly one-third of CK19-positive cells co-expressed GS in acute liver diseases, and chronic cholestatic liver diseases, including primary biliary cholangitis and primary sclerosing cholangitis, showed no co-expression. We also found that DR was longer and had more branching in livers with progressive fibrosis compared to those with regressive fibrosis. Our results suggest that DR displays varying degrees of spatial complexity and contribution to liver regeneration. DR may serve as hepatobiliary junctions that maintain continuity between hepatocytes and bile ducts rather than hepatocyte regeneration in chronic liver diseases. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic kidney disease (CKD) reportedly show dysbiosis, which is the imbalance of gut microbiome. Dysbiosis increases the uremic toxin level in the intestine, and uremic toxins transfer into the blood, causing CKD progression. Sake lees, a traditional Japanese fermented food, may help reduce uremic toxins by altering the gut microbiome. Additionally, D-alanine, which is present in sake lees, may have a renoprotective effect. The present pilot study aims to evaluate the effect of adding sake lees to the standard CKD dietary therapy in reducing blood uremic toxins. Methods: This pilot study is a single-center, open-label, randomized controlled trial. Twenty-four patients with CKD will be enrolled and allocated 1:1 to the intervention and control groups. The intervention group will receive standard CKD dietary therapy with an additional intake of 50 g of sake lees per day for 8 weeks, whereas the control group will only receive standard CKD dietary therapy. The primary endpoint is the change in serum indoxyl sulfate after 8 weeks. The secondary endpoint is the plasma D-alanine and fecal microbiome changes. Conclusion: This pilot study provides insight into the development of a new diet focused on gut microbiome and D-amino acids in patients with CKD. Clinical trial registration: This protocol was approved by the Clinical Trial Review Board of Kanazawa University Hospital on October 27, 2022 (2022-001 [6139]) and available to the public on the website of the Japan Registry of Clinical Trials on November 22, 2022 (jRCT1040220095). [ABSTRACT FROM AUTHOR]

The increasing sulfur content in fossil fuels and the use of biogas as a renewable energy source has highlighted the need for effective desulfurization processes. To remove sulfur species from gaseous resources efficiently, a catalytic process that can convert sulfur compounds to hydrogen sulfide (H2S) at low temperatures is desirable. In this study, electric-field-assisted catalytic methanethiol (CH3SH) decomposition was performed to develop a new system for converting sulfur compounds to H2S at low temperatures. In the thermal catalytic reaction using the Pt/CeO2 catalyst, dimethyl sulfide, which is a byproduct of the reaction, is formed. Compared with the result, applying an electric field suppressed the side reaction. The CH4 and H2S formation rates slightly improved by applying the electric field, suggesting the possibility of controlling the CH3SH decomposition products. [ABSTRACT FROM AUTHOR]

A progeroid family was found to harbor a pathogenic variant in the CASP5 gene that encodes inflammatory caspase 5. Caspase 5-depleted fibroblasts exhibited hyper-activation of inflammatory cytokines in response to pro-inflammatory stimuli. Long-term intermittent hyper-inflammatory response is likely the cause of the accelerated aging phenotype comprised of earlier onset of common aging diseases, supporting inflammaging as a potential common disease mechanism of progeroid syndromes and possibly normative aging. [ABSTRACT FROM AUTHOR]

Purpose: Given the uncertainty surrounding the abscopal effect (AE), it is imperative to identify promising treatment targets. In this study, we aimed to explore the incidence of AE when administering radiotherapy to patients with oligoprogressive solid tumours while they are undergoing treatment with immune checkpoint inhibitors (ICIs). Materials and methods: In this multicentre prospective observational study, oligoprogressive disease was defined as a < 20% increase in lesions compared to > 2 months before enrolment. We enrolled patients who requested radiotherapy during the ICI rest period between 2020 and 2023. AE was considered present if ≥ 1 non-irradiated lesion decreased by ≥ 30% before the next line of systemic therapy started. Results: Twelve patients were included in this study; the common primary lesions were in the lungs (four patients) and kidneys (three patients). AEs were observed in six (50%) patients, with a median time to onset of 4 (range 2–9) months after radiotherapy. No significant predictors of AEs were identified. Patients in the AE group had a significantly better 1-year progression-free survival (PFS) rate than those in the non-AE group (p = 0.008). Two patients from the AE group were untreated and progression-free at the last follow-up. Four (33%) patients experienced grade 2 toxicity, with two cases attributed to radiotherapy and the other two to ICI treatment. No grade 3 or higher toxicities were observed in any category. Conclusion: Patients with oligoprogressive disease may be promising targets with potential for AEs. AEs can lead to improved PFS and, in rare cases, to a certain progression-free period without treatment. Irradiating solid tumours in patients with oligoprogressive disease during immune checkpoint inhibitor therapy may be a promising target with the potential for abscopal effects (AEs). AEs can lead to improved progression-free survival and, in rare cases, to a certain progression-free period without treatment. [ABSTRACT FROM AUTHOR]

This prospective multicenter study aimed to determine the effects of human herpesvirus-6B (HHV-6B) reactivation on central nervous system (CNS) function in cord blood transplant (CBT) recipients. Our focus was to track HHV-6B reactivation and evaluate its association with delirium and cognitive function, specifically in the domains of verbal memory, attention/processing speed, and quality of life (QOL). A cohort of 38 patients participated in this study. Of the 37 patients evaluated, seven (18.9%) developed delirium, with six of these cases emerging after HHV-6B reactivation (median lag, 7 days). Evaluation of verbal memory showed that the final trial score for unrelated words at 70 days after transplantation was significantly lower than that before preconditioning (P = 0.004) among patients (n = 15) who experienced higher-level HHV-6B reactivation (median or higher maximum plasma HHV-6 DNA load for participating patients). Patients without higher-level reactivation did not show significant declines in verbal memory scores. QOL was assessed using the 36-item Short-Form Health Survey, and the social functioning score 1 year post-transplantation was significantly lower in patients who experienced higher-level HHV-6B reactivation than in those who did not. Our findings suggest that higher-level HHV-6B reactivation can detrimentally affect certain cognitive functions in CBT recipients. [ABSTRACT FROM AUTHOR]

We introduce a new elliptic quantum toroidal algebra U q , κ , p (g tor) associated with an arbitrary toroidal algebra g tor . We show that U q , κ , p (g tor) contains two elliptic quantum algebras associated with a corresponding affine Lie algebra g ^ as subalgebras. They are analogue of the horizontal and the vertical subalgebras in the quantum toroidal algebra U q , κ (g tor) . A Hopf algebroid structure is introduced as a co-algebra structure of U q , κ , p (g tor) using the Drinfeld comultiplication. We also investigate the Z-algebra structure of U q , κ , p (g tor) and show that the Z-algebra governs the irreducibility of the level (k (≠ 0) , l) -infinite dimensional U q , κ , p (g tor) -modules in the same way as in the elliptic quantum group U q , p (g ^) . As an example, we construct the level (1, l) irreducible representation of U q , κ , p (g tor) for the simply laced g tor . We also construct the level (0, 1) representation of U q , κ , p (gl N , t o r) and discuss a conjecture on its geometric interpretation as an action on the torus equivariant elliptic cohomology of the affine A N - 1 quiver variety. [ABSTRACT FROM AUTHOR]

Introduction: Immune-related adverse events (irAEs) due to immune checkpoint inhibitors may lead to discontinuation and treatment-related death. Acute aortitis is a rare but severe irAE. Case presentation: A 67-year-old man with recurrent lower gingival carcinoma received nivolumab therapy. Twenty-three months later, he experienced chest compression, which resulted in syncope. Following a whole-body computed tomography (CT) scanning, which revealed diffuse thickening of the aorta, and systemic assessments of the causes of aortitis, he was diagnosed with acute aortitis due to irAE. Nivolumab discontinuation and oral steroids improved CT findings. However, 11 months after nivolumab discontinuation, he developed an aortic aneurysmal rupture. Endovascular aortic repair rescued him. A durable anti-cancer response was still observed 4 months after the aortic rupture. Conclusion: Although severe irAE, such as acute aortitis, occurred, the patient may still achieve a durable response. A broad examination and prompt treatment of irAE can help improve the patient's survival. [ABSTRACT FROM AUTHOR]

Risk factors for pacemaker-induced cardiomyopathy (PICM) have been previously reported, including a high burden of right ventricular pacing, lower left ventricular ejection fraction, a wide QRS duration, and left bundle branch block before pacemaker implantation (PMI). However, predicting the development of PICM remains challenging. This study aimed to use a convolutional neural network (CNN) model, based on clinical findings before PMI, to predict the development of PICM. Out of a total of 561 patients with dual-chamber PMI, 165 (mean age 71.6 years, 89 men [53.9%]) who underwent echocardiography both before and after dual-chamber PMI were enrolled. During a mean follow-up period of 1.7 years, 47 patients developed PICM. A CNN algorithm for prediction of the development of PICM was constructed based on a dataset prior to PMI that included 31 variables such as age, sex, body mass index, left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left atrial diameter, severity of mitral regurgitation, severity of tricuspid regurgitation, ischemic heart disease, diabetes mellitus, hypertension, heart failure, New York Heart Association class, atrial fibrillation, the etiology of bradycardia (sick sinus syndrome or atrioventricular block) , right ventricular (RV) lead tip position (apex, septum, left bundle, His bundle, RV outflow tract), left bundle branch block, QRS duration, white blood cell count, haemoglobin, platelet count, serum total protein, albumin, aspartate transaminase, alanine transaminase, estimated glomerular filtration rate, sodium, potassium, C-reactive protein, and brain natriuretic peptide. The accuracy, sensitivity, specificity, and area under the curve of the CNN model were 75.8%, 55.6%, 83.3% and 0.78 respectively. The CNN model could accurately predict the development of PICM using clinical findings before PMI. This model could be useful for screening patients at risk of developing PICM, ensuring timely upgrades to physiological pacing to avoid missing the optimal intervention window. [ABSTRACT FROM AUTHOR]

In the present paper, we study an upper escape rate of some time inhomogeneous diffusion process associated with a family of regular and local Dirichlet forms. In particular, by making full use of Gaussian type's heat kernel estimates, we establish integral tests for an upper rate function of the time inhomogeneous diffusion process with a coefficient that is not necessarily bounded concerning space and time. [ABSTRACT FROM AUTHOR]

Therapy for relapsed or refractory (r/r) T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in children is challenging, and new treatment methods are needed. We retrospectively analyzed eight patients with r/r T-ALL (five patients) and T-LBL (three patients) who were treated with nelarabine (NEL) plus etoposide, cyclophosphamide, and intrathecal therapy, administered 3 days apart. Five patients achieved a complete response, and the other three achieved a partial response (PR). All patients underwent hematopoietic stem cell transplantation (HSCT) after two cycles of treatment, except for one patient who received one cycle. Three patients who had previously received HSCT were treated with reduced-intensity conditioning regimens, including fludarabine, melphalan, and NEL; one survived for over 5 years after the second HSCT. Grade 2 neuropathy occurred in one patient, but other severe toxicities commonly associated with NEL were not observed during NEL administration in combination with chemotherapy. The 2-year overall survival and event-free survival rates were 60.0% and 36.5%, respectively. The addition of NEL to reinduction chemotherapy was useful in achieving remission and did not lead to excessive toxicity. In addition, a conditioning regimen, including NEL, appeared to be effective in patients who had previously undergone HSCT. [ABSTRACT FROM AUTHOR]

G-protein-coupled receptor class 5 member D (GPRC5D) is detected in malignant plasma cells in approximately 90% of patients diagnosed with multiple myeloma (MM). Here, we constructed BsAb5003, a novel humanized bispecific monoclonal antibody targeting CD3 and GPRC5D, and evaluated its therapeutic impact on MM. BsAb5003 induced specific cytotoxicity of GPRC5D-positive MM cells with concomitant T cell activation and cytokine release. The efficacy of BsAb5003 was associated with GPRC5D expression levels in MM cell lines. Flow cytometry analysis of bone marrow mononuclear cells (BMMNCs) from 49 MM patients revealed that GPRC5D was expressed in a wide population of MM patients, including heavily treated and high-risk patients. In ex vivo assays using BMMNCs, BsAb5003 induced potent efficacy against CD138 + MM cells in both newly diagnosed and relapsed/refractory patient samples in a GPRC5D expression-dependent manner. BsAb5003 significantly enhanced T cell activation and cytokine production in combination with immunomodulatory drugs (IMiDs) against MM cell lines. BsAb5003 also demonstrated significant inhibition of in vivo tumor growth by recruiting T cells. Taken together, these results suggest that T cell-redirecting bispecific antibody targeting GPRC5D as monotherapy and combination therapy with IMiDs could be a highly potent and effective treatment approach for a wide population of MM patients. [ABSTRACT FROM AUTHOR]

Aim: Recently, change in the neutrophil to lymphocyte ratio (cNLR) has been shown to be a promising prognostic inflammation marker in some malignancies. The aim of the present study was to evaluate the clinical impact of the cNLR in gastric cancer patients who received curative gastrectomy. Patients and Methods: The present study included 450 patients who underwent curative treatment for gastric cancer between 2013 and 2017 at Kanagawa Cancer Center. The cNLR was defined as follows: cNLR = NLR at 1 month after surgery–NLR at 1 week before surgery. The prognosis and clinicopathological parameters of the increased cNLR and decreased cNLR groups were analyzed. Results: The OS stratified by each clinical factor was compared using the log-rank test, and a significant difference was observed using a cutoff value of cNLR at 0.762. When comparing the patient background factors between the increased cNLR (≥ 0.762) and decreased cNLR (< 0.762) groups, there were no significant differences in age, sex, T status, or N status. In the increased cNLR group, the OS rates at 3 and 5 years after surgery were 87.5% and 77.3%, respectively, while those in the decreased cNLR group were 92.8% and 87.3%, which amounted to a statistically significant difference (p = 0.041). The univariate and multivariate analyses of factors associated with OS showed that cNLR was a significant prognostic factor. When the postoperative course was compared between the two groups, the incidence rates of postoperative surgical complications and other-cause death were significantly higher in the increased cNLR group (p = 0.001 and p = 0.005, respectively). Conclusion: The cNLR is one of the significant risk factors in gastric cancer patients. Our results suggested that the changes of inflammation status during perioperative periods might be a promising prognostic factor for gastrointestinal cancer patients. [ABSTRACT FROM AUTHOR]

Background: Recently, change in the C-reactive protein/albumin ratio (CAR) has become a promising prognostic marker in some malignancies. The aim of the present study was to evaluate the clinical impact of change in the CAR in gastric cancer patients who received curative resection. Method: The present study included 458 patients who underwent curative treatment for gastric cancer between 2013 and 2017. The prognosis and clinicopathological parameters were compared between patients who showed a high-change in CAR and those who showed a low-change in CAR. Results: The OS stratified by each clinical factor was compared using a log-rank test, and a significant difference was observed using a 0.05 change in CAR. When the patient background factors were compared between the high-change (change in CAR ≥ 0.05) and low-change (change in CAR < 0.05) groups, the median age, sex ratio, T factor, and N factor were similar. In the low-change group, the OS rates at 3 and 5 years after surgery were 94.1% and 87.6%, respectively, which amounted to a significant difference from the low-change group, with rates of 83.6 and 77.5% in the high-change group. In the low-change group, the RFS rates at 3 and 5 years after surgery were 90.1% and 85.1%, respectively, while those in the high-change group 77.6 and 75.2%. The univariate and multivariate analyses of factors associated with OS and RFS showed that the change in CAR was a significant prognostic factor. Conclusions: The change in CAR is a significant risk factor and promising prognostic factor for gastric cancer patients. [ABSTRACT FROM AUTHOR]

This study focused on the dosimetric impact of variations in respiratory motion during lung stereotactic body radiotherapy (SBRT). Dosimetric comparisons between volumetric modulated arc therapy (VMAT) and three-dimensional conformal radiotherapy (3DCRT) were performed using four-dimensional computed tomography (4DCT)-based internal target volumes (ITV). We created retrospective plans for ten patients with lung cancer who underwent SBRT using 3DCRT and VMAT techniques. A Delta4 Phantom + (ScandiDos, Uppsala, Sweden) was used to evaluate the dosimetric robustness of 4DCT-based ITV against variations in respiratory motion during treatment. We analyzed respiratory motion during treatment. Dose–volume histogram parameters were evaluated for the 95% dose (D95%) to the planning target volume (PTV) contoured on CT images obtained under free breathing. The correlations between patient respiratory parameters and dosimetric errors were also evaluated. In the phantom study, the average PTV D95% dose differences for all fractions were − 2.9 ± 4.4% (− 16.0 − 1.2%) and − 2.0 ± 2.8% (− 11.2 − 0.7%) for 3DCRT and VMAT, respectively. The average dose difference was < 3% for both 3DCRT and VMAT; however, in 5 out of 42 fractions in 3DCRT, the difference in PTV D95% was > 10%. Dosimetric errors were correlated with respiratory amplitude and velocity, and differences in respiratory amplitude between 4DCT and treatment days were the main factors causing dosimetric errors. The overall average dose error of the PTV D95% was small; however, both 3DCRT and VMAT cases exceeding 10% error were observed. Larger errors occurred with amplitude variation or baseline drift, indicating limited robustness of 4DCT-based ITV. [ABSTRACT FROM AUTHOR]

Background: Intraductal oncocytic papillary neoplasm (IOPN), previously classified as a subtype of intraductal papillary mucinous neoplasm (IPMN), has been described as an independent disease by the WHO since 2019. IOPN is a rare tumor, with few reported cases. Herein, we report a case of resected non-invasive IOPN that formed a lesion protruding toward the duodenum from the accessory papilla. Case presentation: An 80-year-old woman was referred to our hospital because of a giant mass in the pancreatic head detected on abdominal contrast-enhanced computed tomography (CT) performed for a close examination of a mass in the right breast. CT revealed a 90-mm-sized tumor with a mixture of solid and cystic components, with contrast enhancement in the pancreatic head, and a dilated main pancreatic duct. Esophagogastroduodenoscopy revealed a semi-circumferential papillary tumor protruding toward the duodenal lumen, which did not protrude from the papilla of Vater. Transpapillary biopsy led to a preoperative diagnosis of IPMN with an associated invasive carcinoma. As there were no distant metastasis, open subtotal stomach-preserving pancreaticoduodenectomy was performed. Analysis of the surgical specimen and histopathological examination revealed that the tumor was an IOPN that protruded toward the duodenal mucosa from the accessory papilla while replacing the duodenal mucosa with no obvious stromal invasion. Conclusion: IOPN is a rare and poorly recognized tumor with few reported cases. There have been no reports describing IOPN forming a protruding lesion toward the duodenum from the accessory papilla. Therefore, further accumulation of cases such as this one is important to advance the study of IOPN. [ABSTRACT FROM AUTHOR]

The development of green catalysts, specifically biocatalysts, is crucial for building a sustainable society. To enhance the versatility of biocatalysts, the immobilization of enzymes plays a vital role as it improves their recyclability and robustness. As target enzymes to immobilize, glucose dehydrogenases and carboxylases are particularly important among various kinds of enzymes due to their involvement in two significant reactions: regeneration of the reduced form of coenzyme required for various reactions, and carboxylation reactions utilizing CO2 as a substrate, respectively. In this study, we immobilized Thermoplasma acidophilum glucose dehydrogenase (TaGDH) and T. acidophilum isocitrate dehydrogenase (TaIDH) using a previously reported method involving the formation of enzyme-inorganic hybrid nanocrystals, in the course of our continuing study focusing on carboxylation catalyzed by the free form of TaGDH and TaIDH. Subsequently, we investigated the properties of the resulting immobilized enzymes. Our results indicate the successful immobilization of TaGDH and TaIDH through the formation of hybrid nanocrystals utilizing Mn2+. The immobilization process enhanced TaIDH activity, up to 211%, while TaGDH retained 71% of its original activity. Notably, the immobilized TaGDH exhibited higher activity at temperatures exceeding 87 °C than the free TaGDH. Moreover, these immobilized enzymes could be recycled. Finally, we successfully utilized the immobilized enzymes for the carboxylation of 2-ketoglutaric acid under 1 MPa CO2. In conclusion, this study represents the first immobilization of TaGDH and TaIDH using the hybrid nanocrystal forming method. Furthermore, we achieved significant activity enhancement of TaIDH through immobilization and demonstrated the recyclability of the immobilized enzymes. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the impact of the severity of cervical ossification of the posterior longitudinal ligament (OPLL) on the incidence of arteriosclerosis in the carotid artery. Methods: Patients with OPLL-induced cervical myelopathy were prospectively enrolled. The study involved analyzing patient characteristics, blood samples, computed tomography scans of the spine, and intima-media thickness (IMT) measurements of the common carotid artery. Patients were divided into two groups based on the size of the cervical OPLL to compare demographic data, comorbidities, and the presence of thickening of the carotid intima-media (max IMT ≥ 1.1 mm). Results: The study included 96 patients (mean age: 63.5 years; mean body mass index: 26.9 kg/m2; 71.8% male; 35.4% with diabetes mellitus). The mean maximum anteroposterior (AP) diameter of the OPLL was 4.9 mm, with a mean occupancy ratio of 43%. The mean maximum IMT was 1.23 mm. Arteriosclerosis of the carotid artery was diagnosed in 62.5% of the patients. On comparing the two groups based on OPLL size, the group with larger OPLL (≥ 5 mm) had a higher BMI and a greater prevalence of carotid intima-media thickening. This significant difference in the prevalence of carotid intima-media thickening persisted even after adjusting for patient backgrounds using propensity score matching. Conclusions: Patients with a larger cervical OPLL showed a higher frequency of intima-media thickening in the carotid artery. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy is a new standard for locally advanced esophageal squamous cell carcinoma. The optimal timing of pegfilgrastim with the DCF regimen to prevent febrile neutropenia (FN) remains controversial. The effectiveness of concomitant pegfilgrastim administration with continuous 5-fluorouracil (5-FU) infusion in the DCF regimen was therefore assessed. Methods: All patients who received neoadjuvant DCF for esophageal cancer were retrospectively assessed. Patients who had been scheduled to receive pegfilgrastim on days 3–5 (early group) or days 7–9 (regular group) of the DCF regimen were included. Uni- and multivariate analyses were used to assess risk factors for FN. Results: Eighty-eight patients were included in the analysis. The 26 patients in the early group received pegfilgrastim as scheduled. In the 62 patients of the regular group, 51 received pegfilgrastim at a median of 7 days after starting DCF chemotherapy. However, 11 patients in the regular group could not receive pegfilgrastim. Twenty-two patients of the regular group and 2 patients of the early group developed FN after the first session of DCF. Early administration of pegfilgrastim and grade 4 neutropenia were significantly associated with onset of FN, with multivariate analysis identifying early administration of pegfilgrastim as an independent preventive factor and grade 4 neutropenia as a risk factor, after adjusting for sex and age. Conclusion: Early pegfilgrastim administration is a safe approach that reduces the incidence of FN in DCF therapy. Using pegfilgrastim with continuous 5-FU infusion in the DCF regimen represents a reasonable option to prevent FN. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was thus to compare capabilities for quantitative differentiation of non- and minimally invasive adenocarcinomas from other of pulmonary MRIs with ultra-short TE (UTE) obtained with single- and dual-echo techniques (UTE-MRISingle and UTE-MRIDual) and thin-section CT for stage IA lung cancer patients. Methods: Ninety pathologically diagnosed stage IA lung cancer patients who underwent thin-section standard-dose CT, UTE-MRISingle, and UTE-MRIDual, surgical treatment and pathological examinations were included in this retrospective study. The largest dimension (Dlong), solid portion (solid Dlong), and consolidation/tumor (C/T) ratio of each nodule were assessed. Two-tailed Student's t-tests were performed to compare all indexes obtained with each method between non- and minimally invasive adenocarcinomas and other lung cancers. Receiver operating characteristic (ROC)-based positive tests were performed to determine all feasible threshold values for distinguishing non- or minimally invasive adenocarcinoma (MIA) from other lung cancers. Sensitivity, specificity, and accuracy were then compared by means of McNemar's test. Results: Each index showed significant differences between the two groups (p < 0.0001). Specificities and accuracies of solid Dlong for UTE-MRIDual2nd echo and CTMediastinal were significantly higher than those of solid Dlong for UTE-MRISingle and UTE-MRIDual1st echo and all C/T ratios except CTMediastinal (p < 0.05). Moreover, the specificities and accuracies of solid Dlong and C/T ratio were significantly higher than those of Dlong for each method (p < 0.05). Conclusion: Pulmonary MRI with UTE is considered at least as valuable as thin-section CT for quantitative differentiation of non- and minimally invasive adenocarcinomas from other stage IA lung cancers. Clinical relevance statement: Pulmonary MRI with UTE's capability for quantitative differentiation of non- and minimally invasive adenocarcinomas from other lung cancers in stage IA lung cancer patients is equal or superior to that of thin-section CT. Key Points: • Correlations were excellent for pathologically examined nodules with the largest dimensions (Dlong) and a solid component (solid Dlong) for all indexes (0.95 ≤ r ≤ 0.99, p < 0.0001). • Pathologically examined Dlong and solid Dlong obtained with all methods showed significant differences between non- and minimally invasive adenocarcinomas and other lung cancers (p < 0.0001). • Solid tumor components are most accurately measured by UTE-MRIDual2nd echo and CTMediastinal, whereas the ground-glass component is imaged by UTE-MRIDual1st echo and CTlung with high accuracy. UTE-MRIDual predicts tumor invasiveness with 100% sensitivity and 87.5% specificity at a C/T threshold of 0.5. [ABSTRACT FROM AUTHOR]