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Background: Prehabilitation, which includes nutritional and exercise therapies, is recommended for patients before surgery to improve physical and cognitive functions. This study aimed to identify the awareness, understanding, and issues among surgeons and anesthesiologists regarding the implementation of prehabilitation. Methods: We conducted a survey on prehabilitation targeting surgeons and anesthesiologists working at a university hospital and two private hospitals. The survey collection period was set for 1 month, commencing on February 5, 2024. Descriptive statistics were employed to summarize the characteristics of the participants. Results: A total of 254 surgeons and 49 anesthesiologists from three hospitals participated, with a response rate of 61.7%. Regarding the understanding of prehabilitation, 16.7% of anesthesiologists and only 2% of surgeons had a good grasp of its content. When enquired about the necessity of prehabilitation, 100% of anesthesiologists indicated it as necessary or somewhat necessary, whereas 98.7% of surgeons responded similarly. Several barriers to the implementation of prehabilitation were identified, with the most common reason being the busy schedule of outpatient services. Conclusion: This study highlights that while both surgeons and anesthesiologists recognize the importance of prehabilitation, significant challenges exist in its practical implementation. This underscores the need for simple explanatory tools for patients, the introduction of remote care options, and simple orders to relevant departments, which are essential and require multidisciplinary collaboration. [ABSTRACT FROM AUTHOR]

Real-world data on health-related quality of life (HRQoL) in advanced urothelial carcinoma (aUC) receiving immune checkpoint inhibitors (ICIs) are limited. This study included 42 patients with aUC who received second-line or later pembrolizumab (n = 19), maintenance avelumab followed by first-line chemotherapy (n = 13), or adjuvant nivolumab after radical surgery (n = 10). Time-course changes in the domains and scales related to HRQoL were evaluated using the EORTC QLQ-C30, FACT-G, and SF-8 questionnaires during ICI therapy. Anchor-based approaches for minimally important differences were determined as 'improved', 'stable', and 'deteriorated'. We found significant improvements after the start of pembrolizumab treatment on many scales. Almost none of the scales changed significantly in the avelumab and nivolumab groups. Approximately 80% of the pembrolizumab group had deteriorated social/family well-being in FACT-G. Approximately 60% of the patients in the avelumab group had deteriorated general health and vitality in SF-8. In the nivolumab group, none of the scales deteriorated in > 50% of the patients. Deterioration of physical function in the SF-8 was associated with occurrence of treatment-related adverse events ≥ grade 2 during ICI therapy (P = 0.013). Our findings demonstrated that majority of patients with aUC who received ICI therapy had a stable HRQoL, which was consistent with evidence from clinical trials. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Diabetic retinopathy is characterised by neuroinflammation that drives neuronal and vascular degenerative pathology, which in many individuals can lead to retinal ischaemia and neovascularisation. Infiltrating macrophages and activated retina-resident microglia have been implicated in the progression of diabetic retinopathy, although the distinct roles of these immune cells remain ill-defined. Our aim was to clarify the distinct roles of macrophages/microglia in the pathogenesis of proliferative ischaemic retinopathies. Methods: Murine oxygen-induced retinopathy is commonly used as a model of ischaemia-induced proliferative diabetic retinopathy (PDR). We evaluated the phenotype macrophages/microglia by immunostaining, quantitative real-time RT-PCR (qRT-PCR), flow cytometry and scRNA-seq analysis. In clinical imaging studies of diabetic retinopathy, we used optical coherence tomography (OCT) and OCT angiography. Results: Immunostaining, qRT-PCR and flow cytometry showed expression levels of M1-like macrophages/microglia markers (CD80, CD68 and nitric oxide synthase 2) and M2-like macrophages/microglia markers (CD206, CD163 and macrophage scavenger receptor 1) were upregulated in areas of retinal ischaemia and around neo-vessels, respectively. scRNA-seq analysis of the ischaemic retina revealed distinct ischaemia-related clusters of macrophages/microglia that express M1 markers as well as C-C chemokine receptor 2. Inhibition of Rho-kinase (ROCK) suppressed CCL2 expression and reduced CCR2-positive M1-like macrophages/microglia in areas of ischaemia. Furthermore, the area of retinal ischaemia was reduced by suppressing blood macrophage infiltration not only by ROCK inhibitor and monocyte chemoattractant protein-1 antibody but also by GdCl3. Clinical imaging studies of diabetic retinopathy using OCT indicated potential involvement of macrophages/microglia represented by hyperreflective foci in areas of reduced perfusion. Conclusions/interpretation: These results collectively indicated that heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation in retinal vascular diseases including diabetic retinopathy. This adds important new information that could provide a basis for a more targeted, cell-specific therapeutic approach to prevent progression to sight-threatening PDR. [ABSTRACT FROM AUTHOR]

Purpose: To assess the importance of appropriate opioid administration methods according to nociceptive monitoring. Methods: We conducted a randomized controlled trial involving 54 patients who underwent robot-assisted laparoscopic radical prostatectomy at our hospital. Patients were randomly allocated to either receive nociception level (NOL)-directed intraoperative opioid management with a minimum flow of remifentanil (NOL group) or conventional intraoperative analgesic management (control group). The primary outcome was the mean intraoperative remifentanil infusion flow rate (intraoperative remifentanil usage [μg]/ideal body weight [kg]/operation time [min]). The main secondary outcomes were plasma concentrations of three perioperative inflammatory biomarkers (interleukin-6, C-reactive protein [CRP], and cortisol levels) and postoperative pain (Numeric Rating Scale [NRS]) scores 2 h postoperatively and on postoperative days 1, 2, 3, and 7. Results: Compared with standard analgesia management, NOL-directed analgesic management reduced remifentanil consumption by 20% (– 0.038; 95% confidence interval, – 0.059 to – 0.017; p = 0.0007). NOL-directed management did not lead to an increase in IL-6, CRP, or cortisol levels compared with conventional analgesic management. Furthermore, this protocol led to improvements in the NRS scores at rest 2 h postoperatively and upon movement up to postoperative day 3. Conclusion: NOL-directed analgesic management reduced remifentanil consumption by 20% and the NRS scores at rest 2 h postoperatively and upon movement up to postoperative day 3 without an increase in inflammatory marker levels. Registry number: Japan Registry of Clinical Trials, JRCTs052220034. [ABSTRACT FROM AUTHOR]

The approval of splice-switching oligonucleotides with phosphorodiamidate morpholino oligomers (PMOs) for treating Duchenne muscular dystrophy (DMD) has advanced the field of oligonucleotide therapy. Despite this progress, PMOs encounter challenges such as poor tissue uptake, particularly in the heart, diaphragm, and central nervous system (CNS), thereby affecting patient's prognosis and quality of life. To address these limitations, we have developed a PMOs-based heteroduplex oligonucleotide (HDO) technology. This innovation involves a lipid-ligand-conjugated complementary strand hybridized with PMOs, significantly enhancing delivery to key tissues in mdx mice, normalizing motor functions, muscle pathology, and serum creatine kinase by restoring internal deleted dystrophin expression. Additionally, PMOs-based HDOs normalized cardiac and CNS abnormalities without adverse effects. Our technology increases serum albumin binding to PMOs and improves blood retention and cellular uptake. Here we show that PMOs-based HDOs address the limitations in oligonucleotide therapy for DMD and offer a promising approach for diseases amenable to exon-skipping therapy. Here, the authors develop a PMO-based heteroduplex oligonucleotide technology that enhances PMO delivery to tissues and normalizes motor/cardiac function and CNS symptoms in a mouse model of Duchenne muscular dystrophy. One Sentence Summary: Heteroduplex oligonucleotide technology was applied to morpholino oligomers and normalized motor, cardiac, and central nervous system functions of Duchenne muscular dystrophy model mice. [ABSTRACT FROM AUTHOR]

Biochar is a nature-based solution for sustainable agriculture but its potential adoption in some parts of sub-Saharan Africa is still minimal. In this study, we evaluated the agronomic potential of maize stover biochar in cowpea-maize sequential cropping in Uganda under field conditions. The treatments included; the common farmer practice of no inorganic fertilizer and no biochar (CTR), inorganic fertilizer (F), 10 t ha−1 biochar (B10), 40 t ha−1 biochar (B40), 10 t ha−1 biochar + inorganic Fertilizer (FB10), and 40 t ha−1 biochar + inorganic Fertilizer (FB40), arranged in a randomized complete block design (RCBD) with three replications. The results showed that cowpea seed yield was not significantly affected by biochar and fertilizer application but the haulm yield was significantly improved only in FB40 treatment. Maize grain and stover yield was significantly improved only in the FB40 treatment but biochar showed a high potential to also improve yield even without inorganic fertilizer. The potential for biochar to improve maize yield either in the presence or absence of fertilizers could be attributed to the residual soil fertility from cowpeas. In both seasons, biochar significantly improved soil pH, EC, SOC, total N, available P, exchangeable K and Ca, irrespective of fertilizer application. However, exchangeable Mg did not significantly vary among the treatments. This study further revealed that in cowpea-maize rotation, optimum yield could also be possible with sole biochar application. Therefore, instead of burning the maize stovers after harvest, farmers should convert the residues into biochar and return it to the soil so as to achieve sustainable food systems. [ABSTRACT FROM AUTHOR]

Purpose: To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP). Study design: Phase 1/2, multicenter, open-label, single-arm, 12-week clinical trial. Methods: Infants born with gestational age (GA) of ≤ 32 weeks or weight of ≤ 1500 g with zone I or II, ≥ stage 1, ROP in both eyes were enrolled. Ripasudil eye drops were administered to patients in both eyes. Phase 1 was a dose-escalation study (once daily for 1 week, then twice daily for 2 weeks); an additional dosing up to 9 weeks was allowed if no safety issues occurred. In phase 2, ripasudil was administered twice daily for up to 12 weeks. Adverse events were assessed. The proportion of patients with type 1 ROP progression, number of days for type 1 ROP progression, and progression to the most advanced ROP stage were estimated. Results: Twenty-four infants were enrolled (phase 1, n = 3; phase 2, n = 21). Nineteen and four patients experienced systemic and ocular adverse events, respectively. Efficacy endpoints were not different between the ripasudil and historical control groups. However, in the GA ≤ 27 weeks subgroup, fewer patients progressed to type 1 ROP in the ripasudil than in the historical control group (P = 0.09). In the GA ≤ 27 weeks subgroups, the 25th percentile for the number of days for type 1 ROP progression was 22 days in the historical control group and 44 days in the ripasudil group. Conclusion: Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA. [ABSTRACT FROM AUTHOR]

Purpose: Complete androgen insensitivity syndrome (CAIS) and Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) share common clinical features such as female phenotype, vaginal hypoplasia, and primary amenorrhea. Magnetic resonance imaging (MRI) is performed to investigate the cause of primary amenorrhea. However, the MRI features are also similar in both disorders. They are ultimately diagnosed by chromosome testing, but there is a possibility of misdiagnosis if chromosome testing is not performed. This study aimed to identify MRI features that are useful for differentiating CAIS from MRKHS. Method: This multicenter retrospective study included 12 patients with CAIS and 19 patients with MRKHS. Three radiologists blindly evaluated the following features: (1) detection of vagina, (2) detection of nodular and cystic structures in the lateral pelvis; undescended testicles and paratesticular cysts in CAIS and rudimentary uteri and ovaries in MRKHS, (3) their location, (4) number of cysts in the cystic structures, and (5) signal intensity on diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) values of the nodular structures. Statistical comparisons were performed using Mann–Whitney U and Fisher's exact tests. Results: Compared with MRKHS, the CAIS group showed significantly detectable vagina, more ventrally located nodular and cystic structures, fewer cysts within the cystic structures, and nodular structures with higher signal intensity on DWI and lower ADC values. Conclusions: MRI features of detectable vagina, location of nodular and cystic structures, number of cysts within the cystic structures, signal intensity on DWI and ADC values of the nodular structures were useful in differentiating CAIS from MRKHS. [ABSTRACT FROM AUTHOR]

Background: Benign choledochojejunal anastomotic stricture (CJS) is a complication of pancreaticoduodenectomy and choledochojejunostomy. Typically managed with endoscopic balloon dilatation, CJS has a high recurrence rate. Covered metallic stent (CMS) placement is a potential alternative; however, a comprehensive evaluation is lacking. Objectives: The aim of this study was to evaluate the treatment outcomes of CMS placement in patients with CJS. Methods: We retrospectively analyzed patients who underwent balloon dilation via endoscopic retrograde cholangiopancreatography using a double-balloon endoscope for CJS between October 2010 and October 2023. The study outcomes included technical and clinical success rates, adverse event rates, choledochojejunal anastomotic stricture recurrence rates, and time to recurrence for balloon dilation and CMS treatment for CJS. Results: There were 43 patients, 55 procedures (40 balloon dilation and 15 CMS placement). The technical and clinical success rates were 100% for both treatments. Recurrence of CJS was observed in 35% (14/40) of the patients in the balloon dilation group. The recurrence rate was significantly higher in the balloon dilation group than in the CMS group (35% vs. 0%, p = 0.006). The time to CJS recurrence was significantly shorter in the balloon dilation group than in the covered metallic stent group (NR vs. NR, p = 0.03). Conclusion: Placement of CMS for treating patients with CJS was demonstrated to be an effective and safe method with a lower recurrence rate than balloon dilation. [ABSTRACT FROM AUTHOR]

Purpose: Post-operative infectious complication (IC) is a well-known negative prognostic factor, while showing neoadjuvant chemotherapy (NAC) may cancel out the negative influence of IC. This analysis compared the clinical impacts of IC according to the presence or absence of NAC in gastric cancer patients enrolled in the phase III clinical trial (JCOG0501) which compared upfront surgery (arm A) and NAC followed by surgery (arm B) in type 4 and large type 3 gastric cancer. Methods: The subjects were 224 patients who underwent R0 resection out of 316 patients enrolled in JCOG0501. The prognoses of the patients with or without ICs in each arm were investigated by univariable and multivariable Cox regression analyses. Results: There were 21 (20.0%) IC occurrences in arm A and 15 (12.6%) in arm B. In arm A, the overall survival (OS) of patients with ICs was slightly worse than those without IC (3-year OS, 57.1% in patients with ICs, 79.8% in those without ICs; adjusted hazard ratio (95% confidence interval), 1.292 (0.655–2.546)). In arm B, patients with ICs showed a trend of better survival than those without ICs (3-year OS, 80.0% in patients with IC, 74.0% in those without IC; adjusted hazard ratio, 0.573 (0.226–1.456)). Conclusion: This study could not indicate the negative prognostic influence of ICs in gastric cancer patients receiving NAC, which might be canceled by NAC. To build exact evidence, further investigation with prospective and large numbers of data might be expected. [ABSTRACT FROM AUTHOR]

Background: Maintenance avelumab is currently recommended for patients with unresectable and/or metastatic (mUC) achieving at least stable disease (SD) on first-line platinum-based chemotherapy (1L-CT). Pembrolizumab is an alternative therapeutic avenue for this patient cohort in clinical practice. We investigated real-world data, focusing on the correlation between response to 1L-CT and oncological efficacy of subsequent immune checkpoint inhibitor (ICI) therapy with avelumab or pembrolizumab. Methods: A multicenter database registered 626 patients with mUC diagnosed from 2008–2023; among these, 175 receiving 2–6 cycles of 1L-CT followed by ICI therapy. Patients were categorized based on response to 1L-CT using the Response Evaluation Criteria in Solid Tumors (v1.1). Objective response rate on ICI, progression to ICI-free survival (ICI-PFS), and overall survival from start of 1L-CT were compared between avelumab-treated and pembrolizumab-treated patients in each response subgroup. Results: ICI-PFS was significantly longer in patients achieving partial response on 1L-CT and subsequently receiving pembrolizumab compared to those receiving avelumab. Notably, patients achieving SD on 1L-CT and subsequently receiving pembrolizumab manifested significantly higher objective response rate (14% and 41%, respectively) and prolonged ICI-PFS relative to those receiving avelumab. In contrast, overall survival did not delineate difference between patients treated with avelumab versus pembrolizumab. Similar findings were discerned in the subanalysis of patients having favorable SD (tumor shrinkage, from − 29 to 0%) and unfavorable SD (tumor enlargement, from + 1 to + 19%) on 1L-CT. Conclusions: Our study provides real-world evidence regarding difference of oncological efficacy between maintenance avelumab and subsequent pembrolizumab in patients with mUC who achieved partial response or SD on 1L-CT. [ABSTRACT FROM AUTHOR]

Eusocial aphids produce sterile defensive individuals (soldiers) for colony defense. Because soldier production leads to a trade-off between colony growth and colony defense, to realize stable colony growth, the aphids should produce soldiers in response to a changing predation risk. However, the factors affecting soldier production have been revealed in only three species of eusocial aphids, which altogether comprise 40 species. In this study, we investigated the induction of soldier production in the eusocial aphid Ceratovacuna japonica (Hemiptera: Aphididae) by observing colony growth and the reproductive schedule of C. japonica on its secondary host plant Sasa senanensis (Poales: Poaceae) in the laboratory. We hypothesized that soldier production depended on the number of aphid individuals on the host plant. Our results showed that individuals of C. japonica that had just founded their colony on a leaf of the host plant produced only normal individuals, thereby maximizing the population growth rate. Then, after the number of aphid individuals has increased on the host plant, the adults started to produce soldiers for colony defense. Further, newborn aphid individuals that were moved from a leaf having a colony with soldier production to a new leaf without a colony foundation did not produce soldiers after they grew up. This result suggests that C. japonica can flexibly produce soldiers in response to a change in the number of aphid individuals on the host plant. [ABSTRACT FROM AUTHOR]

Background: Adenosquamous carcinoma of the pancreas (ASCP) accounts for only 1–4% of all pancreatic exocrine cancers and has a particularly poor prognosis. The efficacy of chemotherapy for ASCP remains unknown because of the small number of cases, and few studies have evaluated conversion-intended chemotherapy. Case presentation: A 76-year-old woman was referred to our hospital because of epigastric pain and nausea. A preoperative contrast-enhanced multidetector row computed tomography (MDCT) scan revealed a 17 × 17 mm low-density tumor with an ill-defined margin at the arterial phase in the pancreatic head. The tumor involved the common hepatic artery, left hepatic artery bifurcated from the common hepatic artery, and gastroduodenal artery, and was in contact with the portal vein. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed an uptake in the pancreatic head but no evidence of distant metastasis. The tumor was diagnosed as an adenocarcinoma of the pancreatic head and staged unresectable because the common and left hepatic arteries were involved. Hence, the patient underwent seven courses of conversion-intended chemotherapy using gemcitabine and nab-paclitaxel for pancreatic ductal adenocarcinoma over 7 months. After chemotherapy, the tumor shrank to 10 × 10 mm on contrast-enhanced MDCT. Consequently, the boundary between the tumor and major vessels of the common and left hepatic arteries and the portal vein became clear, and the involvement of the arteries with the tumor was evaluated to be released. The contact of the tumor to the portal vein also reduced to less than half the circumference of the portal vein. FDG-PET showed decreased accumulation in the tumor. Hence, the tumor was judged resectable, and pancreaticoduodenectomy was performed. The tumor and major blood vessels were easily dissected and R0 resection was achieved. The patient experienced no major complications and was discharged on postoperative day 28. The tumor was revealed as ASCP via pathological examination. The patient is alive and recurrence-free seven months after surgery. This is the first report of successful R0 resection for an initially unresectable ASCP following conversion-intended chemotherapy using gemcitabine and nab-paclitaxel regimen. Conclusions: Conversion-intended chemotherapy using gemcitabine and nab-paclitaxel regimen may be effective for ASCP. [ABSTRACT FROM AUTHOR]

Gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX are widely used as first-line regimens for unresectable pancreatic cancer (PC). When GnP therapy is selected, considering patient age or condition, second-line FOLFIRINOX is sometimes difficult to administer owing to its toxicity. This study aimed to determine the recommended dose (RD) of S-IROX (S-1, oxaliplatin, and irinotecan combination) regimens in patients with unresectable PC after first-line GnP failure. This phase-I study used the "3 + 3" dose-escalation design with two dose levels. Patients who failed first-line GnP therapy for unresectable PC were enrolled. Oxaliplatin and irinotecan were administered on day 1, and S-1 was administered orally twice daily on days 1–7, followed by 7 days of rest. The primary endpoints were dose-limiting toxicities (DLTs) and determination of RD. The secondary endpoint was the evaluation of potential antitumor activity. Nine patients received the second-line S-IROX regimen. In level-0 (S-1, 80 mg/m2; oxaliplatin, 85 mg/m2; and irinotecan, 120 mg/m2), no patient experienced DLT; however, one patient experienced grade 3 neutropenia. At level-1 (irinotecan increased to 150 mg/m2), one of six patients experienced DLTs, including G3 diarrhea. The RD was confirmed at the level-1 dose. The response rate, disease control rate, median progression-free survival, and median overall survival were 33.3%, 77.8%, 172 (range:77–422) days, and 414 (101–685) days, respectively. One patient underwent surgery after the second-line S-IROX therapy. Second-line S-IROX treatment was deemed acceptable. The RD was set at level-1 dose (S-1, 80 mg/m2; oxaliplatin, 85 mg/m2; and irinotecan, 150 mg/m2). [ABSTRACT FROM AUTHOR]

Purpose: Anthracycline-cyclophosphamide followed by docetaxel-containing chemotherapy is effective for perioperative breast cancer treatment. However, these treatments frequently induce oral mucositis (OM), with an incidence ranging from 20 to 50%. The association of OM development between different chemotherapeutic treatments remains unclear. Consequently, this study aimed to compare OM development during docetaxel-containing chemotherapy between patients with and without OM experience during previous anthracycline-cyclophosphamide treatments to assess the association between OM development and treatment regimens. Methods: Seventy-two patients with breast cancer receiving anthracycline-cyclophosphamide followed by docetaxel-containing chemotherapy as a perioperative treatment were categorized into the control (no prior OM experience with anthracycline-cyclophosphamide) and OM-experience (OM development during previous treatment) groups and retrospectively evaluated. The primary endpoint was the incidence of all-grade OM in the first docetaxel-containing chemotherapy cycle. Additionally, the incidences of OM and dysgeusia during all treatment cycles and factors associated with the incidence of OM were evaluated. Results: The incidence of all-grade OM in the first cycle was significantly higher in the OM-experience group (54.2%) than in the control group (10.4%; P < 0.0001). Furthermore, its incidence in all treatment cycles was higher in the OM-experience group (66.7%) than in the control group (12.5%, P < 0.0001). However, the incidence of dysgeusia did not differ between the groups. Multivariate logistic regression analysis revealed OM experience during previous anthracycline-cyclophosphamide treatment and concomitant pertuzumab use as independent risk factors for OM development in subsequent docetaxel-containing chemotherapy. Conclusion: Our study suggests that patients experiencing OM with anthracycline-cyclophosphamide during perioperative breast cancer treatment exhibit symptoms following subsequent docetaxel-containing chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Pelvic exenteration (PE) is the last resort for achieving a complete cure for pelvic cancer; however, it is burdensome for patients. Minimally invasive surgeries, including robot-assisted surgery, have been widely used to treat malignant tumors and have also recently been used in PE. This study aimed to evaluate the safety and efficacy of robot-assisted PE (RPE) by comparing the outcomes of open PE (OPE) with those of conventional laparoscopic PE (LPE) for treating pelvic tumors. Methods: Following the ethics committee approval, a multicenter retrospective analysis of patients who underwent pelvic exenteration between January 2012 and October 2022 was conducted. Data on patient demographics, tumor characteristics, and perioperative outcomes were collected. A 1:1 propensity score-matched analysis was performed to minimize group selection bias. Results: In total, 261 patients met the study criteria, of whom 61 underwent RPE, 90 underwent OPE, and 110 underwent LPE. After propensity score matching, 50 pairs were created for RPE and OPE and 59 for RPE and LPE. RPE was associated with significantly less blood loss (RPE vs. OPE: 408 mL vs. 2385 ml, p < 0.001), lower transfusion rate (RPE vs. OPE: 32% vs. 82%, p < 0.001), and lower rate of complications over Clavien–Dindo grade II (RPE vs. OPE: 48% vs. 74%, p = 0.013; RPE vs. LPE: 48% vs. 76%, p = 0.002). Conclusion: This multicenter study suggests that RPE reduces blood loss and transfusion compared with OPE and has a lower rate of complications compared with OPE and LPE in patients with locally advanced and recurrent pelvic tumors. [ABSTRACT FROM AUTHOR]

Purpose: Ultrasound-guided supraclavicular catheterization (UGSC) of the brachiocephalic vein (BCV) for long-term tunneled central venous catheter (tCVC) insertion may be safer than the internal jugular vein approach due to its superior field of view. We examined the clinical outcomes of tCVC insertions performed by junior residents through UGSC of the BCV. Patients and methods: From January 2018 to December 2023, we assessed clinical outcomes and compared the experience levels of surgeons conducting tCVC insertions. Surgeons were categorized into three groups: junior residency (JR), senior residency (SR), and board-certified pediatric surgeons (BCPS). Results: 177 tCVC insertions were done on 146 patients. Intraoperative complications included 6 cases of arterial puncture, 1 case of pneumothorax, 1 case of over insertion of catheter tip, and 1 case of suspected hemothorax. Distribution across groups was as follows: 28 cases (15.8%) in JR group, 92 (52.0%) in SR group, and 57 (32.2%) in BCPS group. Although the JR group exhibited longer operation times than the BCPS group, no significant differences in intraoperative complications were noted. Conclusion: Junior residents can safely perform UGSC for tCVC insertion. However, careful consideration of complications such as arterial or thoracic puncture is essential and case selection should be based on experience. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated portal hypertension (PHT) and its predictors among native liver survivors (NLS) of biliary atresia (BA) after Kasai portoenterostomy (KPE). Methods: This was a multicenter study using prospectively collected data. The subjects were patients who remained transplant-free for 5 years after KPE. Their status of PHT was evaluated and variables that predicted PHT were determined by regression analysis and receiver operating characteristic (ROC) curve. Results: Six centers from East Asia participated in this study and 320 subjects with KPE between 1980 to 2018 were analyzed. The mean follow-up period was 10.6 ± 6.2 years. At the 5th year after KPE, PHT was found in 37.8% of the subjects (n = 121). Patients with KPE done before day 41 of life had the lowest percentage of PHT compared to operation at older age. At 12 months after KPE, PHT + ve subjects had a higher bilirubin level (27.1 ± 11.7 vs 12.3 ± 7.9 µmol/L, p = 0.000) and persistent jaundice conferred a higher risk for PHT (OR = 12.9 [9.2–15.4], p = 0.000). ROC analysis demonstrated that a bilirubin level above 38 µmol/L at 12 months after KPE predicted PHT development (sensitivity: 78%, specificity: 60%, AUROC: 0.75). Conclusions: In BA, early KPE protects against the development of PHT among NLSs. Patients with persistent cholestasis at one year after KPE are at a higher risk of this complication. They should receive a more vigilant follow-up. Level of evidence: Level III [ABSTRACT FROM AUTHOR]

Purpose: Frequent post-operative cholangitis in biliary atresia (BA) affects the long-term native liver survival. This study assessed the characteristics of early cholangitis and their influence on the prognosis. Methods: Forty-three patients with BA who underwent surgery between 2000 and 2020 were analyzed for routine inflammatory markers. Early cholangitis characteristics were compared between native liver survivor (NLS) and living donor liver transplant (LDLT) patients. Results: Among the 43 patients, 30 (69.8%) experienced 130 episodes of cholangitis. In the area under the receiver operating characteristics curve (AUROC) analysis, the cutoff value of the total cholangitis episodes was 3, with an area under the AUROC curve of 0.695 (95% confidence interval 0.522–0.868). Before 3 years old, 113 episodes (86.9%) of cholangitis were observed. The white blood cell, C-reactive protein, and alanine aminotransferase values at cholangitis onset did not markedly differ between the LDLT and NLS groups. Conversely, the neutrophil-to-lymphocyte ratio in the NLS group was significantly lower than in the LDLT group (0.85 vs. 1.63, p < 0.001). Conclusions: Cholangitis in the NLS group was lymphocyte-dominant and atypical in its pathogenesis. Lymphocyte-dominant cholangitis is non-suppurative, and future research should clarify its pathogenesis to improve the treatment and prognosis of BA. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the impact of hepatocyte growth factor (HGF) on colonic morphology and gut microbiota in a rat model of short bowel syndrome (SBS). Methods: SD rats underwent jugular vein catheterization for total parenteral nutrition (TPN) and 90% small bowel resection [TPN + SBS (control group) or TPN + SBS + intravenous HGF (0.3 mg/kg/day, HGF group)]. Rats were harvested on day 7. Colonic morphology, gut microflora, tight junction, and Toll-like receptor-4 (TLR4) were evaluated. Results: No significant differences were observed in the colonic morphological assessment. No significant differences were observed in the expression of tight junction-related genes in the proximal colon. However, the claudin-1 expression tended to increase and the claudin-3 expression tended to decrease in the distal colon of the HGF group. The Verrucomicrobiota in the gut microflora of the colon tended to increase in the HGF group. The abundance of most LPS-producing microbiota was lower in the HGF group than in the control group. The gene expression of TLR4 was significantly downregulated in the distal colon of the HGF group. Conclusion: HGF may enhance the mucus barrier through the tight junctions or gut microbiome in the distal colon. [ABSTRACT FROM AUTHOR]

The liver is a vital organ involved in nutrient metabolism, hormone regulation, immunity, cytokine production, and gut homeostasis. Impairment in liver function can result in malnutrition, chronic inflammation, decreased anabolic hormone levels, and dysbiosis. These conditions eventually cause an imbalance in osteoblast and osteoclast activities, resulting in bone loss. Osteoporosis is a frequent complication of chronic liver disease (CLD) that adversely affects quality of life and increases early mortality. Sarcopenia is another common complication of CLD characterized by progressive loss of skeletal muscle mass and function. Assessment criteria for sarcopenia specific to liver disease have been established, and sarcopenia has been reported to be associated with an increase in the risk of liver disease-related events and mortality in patients with CLD. Owing to their similar risk factors and underlying pathophysiological mechanisms, osteoporosis and sarcopenia often coexist (termed osteosarcopenia), progress in parallel, and further exacerbate the conditions mentioned above. Therefore, comprehensive management of these musculoskeletal disorders is imperative. This review summarizes the clinical implications and characteristics of osteoporosis, extending to sarcopenia and osteosarcopenia, in patients with CLD caused by different etiologies. [ABSTRACT FROM AUTHOR]

Visual function comprises three principles: light sensation, color sensation, and minimum separable sensation. Although clinical evaluation of light sensation and visual acuity have been remarkably developed through comprehensive application of various methods, the test methods to evaluate color sensation in the clinical field have not reflected these various significant developments after their recommendation at the International Congress of Ophthalmology in 1933. To date, various research methods in color vision have been invented on the basis of clinical evaluation methods, most of which were limited to laboratory investigations and were not applied to the clinical field. In this review, the author focuses on both the currently clinical available evaluation methods and the clinically applicable methods based on the present laboratory research studies. [ABSTRACT FROM AUTHOR]

Purpose: To clarify the diagnostic utility and formation of the Mille-feuille sign for ovarian carcinosarcoma (OCS) on MRI, and to evaluate the other MRI findings and serum markers compared to ovarian metastases from colorectal carcinoma (OMCRC). Method: Three blinded radiologists retrospectively reviewed MR images of 12 patients with OCS, 18 with OMCRC, and 40 with primary ovarian carcinoma (POC) identified by the electronic database of radiology reports. The interobserver agreement was analyzed using Fleiss' kappa test. Their MRI characteristics and tumor markers were compared using Fisher's exact test and Mann–Whitney's U test. Receiver operating characteristic curve analyses were used to determine the cutoff points for the ADC value. This study was approved by the institutional ethics committee. Results: Interobserver agreement analysis was moderate or higher for all MRI characteristics. The frequency of Mille-feuille sign was comparable for both OCS and OMCRC groups, and predominantly higher than that of the POC group (p < 0.001, p < 0.001), respectively. Pathologically, the Mille-feuille sign in OCS reflected alternating layers of tumor cells with stroma and necrosis or intraluminal necrotic debris. Compared to OMCRC, intratumoral hemorrhage (p = 0.02), margin irregularity (p = 0.048), unilateral adnexal mass (p = 0.02), and low ADC values (p < 0.01) were more frequently observed and serum CEA levels was significantly lower (p = 0.007) in the OCS group. Under setting of the cutoff value of ADC at 0.871 × 10−3mm2/s, the discriminative ability for OCS showed 66.7% sensitivity, 94.4% specificity, and 81.0% accuracy, respectively. Conclusions: The Mille-feuille sign was seen in both OCS and OMCRC. MR findings of intratumoral hemorrhage, margin irregularity, unilateral adnexal mass, low ADC values, and low serum CEA levels can be useful in differentiating OCS from OMCRC. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the usefulness of machine learning (ML) models using pretreatment 18F-FDG-PET-based radiomic features for predicting adverse clinical events (ACEs) in patients with cardiac sarcoidosis (CS). Materials and methods: This retrospective study included 47 patients with CS who underwent 18F-FDG-PET/CT scan before treatment. The lesions were assigned to the training (n = 38) and testing (n = 9) cohorts. In total, 49 18F-FDG-PET-based radiomic features and the visibility of right ventricle 18F-FDG uptake were used to predict ACEs using seven different ML algorithms (namely, decision tree, random forest [RF], neural network, k-nearest neighbors, Naïve Bayes, logistic regression, and support vector machine [SVM]) with tenfold cross-validation and the synthetic minority over-sampling technique. The ML models were constructed using the top four features ranked by the decrease in Gini impurity. The AUCs and accuracies were used to compare predictive performances. Results: Patients who developed ACEs presented with a significantly higher surface area and gray level run length matrix run length non-uniformity (GLRLM_RLNU), and lower neighborhood gray-tone difference matrix_coarseness and sphericity than those without ACEs (each, p < 0.05). In the training cohort, all seven ML algorithms had a good classification performance with AUC values of > 0.80 (range: 0.841–0.944). In the testing cohort, the RF algorithm had the highest AUC and accuracy (88.9% [8/9]) with a similar classification performance between training and testing cohorts (AUC: 0.945 vs 0.889). GLRLM_RLNU was the most important feature of the modeling process of this RF algorithm. Conclusion: ML analyses using 18F-FDG-PET-based radiomic features may be useful for predicting ACEs in patients with CS. [ABSTRACT FROM AUTHOR]

This work reports a selective median crack propagation phenomenon in glass, leading to a novel glass cutting process. We found that by scribing a glass sample to the extent of plastic deformation with a deformation depth of 100–400 nm, followed by inducing an initial crack, a subsurface crack with a depth of ~ 10 μm was propagated backward along the centerline of the scribed region with a speed of 1 μm/s order. The crack depth and propagation speed were increased by increasing the scribing load. We conclude that the propagation direction was determined by the effect of the shear stress caused by a scribing tip sliding motion. [ABSTRACT FROM AUTHOR]

Background: Nivolumab plus ipilimumab (NIVO + IPI) is the first-line treatment for patients with metastatic renal cell carcinoma (mRCC). While approximately 40% of patients treated with NIVO + IPI achieve a durable response, 20% develop primary resistance with severe consequences. Therefore, there is a clinical need for criteria to select patients suitable for NIVO + IPI therapy to optimize its therapeutic efficacy. Accordingly, our aim was to evaluate the association between candidate biomarkers measured before treatment initiation and survival. Methods: This was a multi-institutional, retrospective, cohort study of 183 patients with mRCC treated with systematic therapies between August 2015 and July 2023. Of these, 112 received NIVO + IPI as first-line therapy: mean age, 68 years; men, 83.0% (n = 93), and clear cell histology, 80.4% (n = 90). Univariable and multivariable analyses were used to evaluate associations between biomarkers and survival. Results: On univariate analysis, high C-reactive protein and systemic index, a high neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio, and a low lymphocyte-to-monocyte ratio (LMR) were associated with shorter overall survival (OS). On multivariable analysis, a LMR ≤ 3 was retained as an independent factor associated to shorter OS with the highest accuracy (C-index, 0.656; hazard ratio, 7.042; 95% confidence interval, 2.0–25.0; p = 0.002). Conclusion: A low LMR may identify patients who would be candidate for NIVO + IPI therapy for mRCC. [ABSTRACT FROM AUTHOR]

Background and purpose: Because myxoid liposarcomas are more radiosensitive than other soft tissue sarcomas, there have been several reports of 50 Gy preoperative radiation therapy combined with surgery, but the wound complication rate is reportedly high. We have performed preoperative irradiation at a reduced dose of 40 Gy and definitive radiation therapy for unresectable cases. This study aimed to report the tumor reduction rate and oncological results with a reduced dose of preoperative irradiation and the outcome of definitive irradiation for unresectable cases. Materials and methods: Forty-one patients with myxoid liposarcoma treated in our institution between 2002 and 2021 were included. We examined the tumor volume shrinkage rate with preoperative radiation, compared complications and oncological outcomes between preoperative radiation and surgery-only cases, and investigated the prognosis and tumor shrinkage of definitive radiation cases. Results: The total dose irradiated was 40 Gy except in two cases. The mean tumor volume reduction rate was 52.0%. A decreased dose of preoperative radiation did not worsen clinical outcomes with fewer complications. The total dose of definitive radiation was approximately 60 Gy. The mean tumor volume reduction rate was 55.0%. The tumor shrinkage maintenance rate was 100% in a median follow-up period of 50.5 months. Conclusion: Preoperative radiation therapy for myxoid liposarcoma near vital organs is a good approach because even with a reduced dose of 40 Gy, significant tumor reduction and excellent results were achieved. Definitive radiation therapy is the recommended treatment for older patients with serious comorbidities or inoperable patients. [ABSTRACT FROM AUTHOR]

Objectives: The current study aimed to examine the incidence of perioperative infections and graft viability in ABO-compatible and ABO-incompatible renal transplant recipients. Methods: We included 643 living donor renal transplant recipients registered in the Michinoku Renal Transplant Network from 1998 to 2021. Patients were divided into the ABO-compatible and ABO-incompatible kidney transplantation groups. We compared the characteristics of the two groups and evaluated the incidence of postoperative viral infections (cytomegalovirus and BK virus), graft loss-free survival, and overall survival between the two groups. Results: Of 643 patients, 485 (75%) and 158 (25%) were ABO-compatible and ABO-incompatible renal transplant recipients, respectively. Postoperative viral infections, rituximab use, and plasma exchange were significantly more common in ABO-incompatible than in ABO-compatible transplant recipients. However, there were no significant differences in terms of other background characteristics. The ABO-incompatible group was more likely to develop viral infections than the ABO-compatible group. Graft loss-free survival and overall survival did not significantly differ between the two groups. According to the multivariate Cox regression analysis, ABO compatibility was not significantly associated with graft loss-free survival and overall survival. Conclusion: Although the incidence of postoperative viral infections in ABO-incompatible renal transplant recipients increased, there was no significant difference in terms of rejection events, graft loss-free survival, and overall survival. [ABSTRACT FROM AUTHOR]

Background: Ovarian endometriomas (OEs) are rarely found in the pediatric population, especially before menstruation. We report a 6-year-old girl who was postoperatively diagnosed with OE before menstruation. Case presentation: A 6-year-old girl presented to a local pediatrician with abdominal pain and vomiting. Abdominal ultrasonography revealed a multilocular cystic lesion to the left of the bladder. Magnetic resonance imaging (MRI) revealed similar findings, with the contents of the cyst showing a low signal on T1-weighted imaging and a high signal on T2-weighted imaging. The patient was referred to our institution for further examination. Enhanced computed tomography (CT) showed a multilocular cystic lesion sized 56 × 44 × 30 mm with partial calcification. The left ovarian vein was dilated, suggesting the origin of the tumor to be the left ovary. Extirpation of the lesion was performed under laparoscopic assistance. Pathological findings indicated an ovarian endometrioma. To our knowledge, this is the youngest report of an OE diagnosed in a patient prior to menstruation. Conclusions: OEs in children before menstruation are extremely rare; thus, the long-term prognosis is yet to be determined. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the hemodynamic effects of remimazolam- and propofol-based total intravenous anesthesia in patients who underwent transcatheter aortic valve replacement. Methods: This was a single-center, single-blind, randomized controlled trial set at Nara Medical University, Kashihara, Japan. We included 36 patients aged ≥ 20 years scheduled to undergo elective transfemoral transcatheter aortic valve replacement (TAVR) under general anesthesia. The participants were randomly assigned to the remimazolam and propofol groups (n = 18 each). Remimazolam- or propofol-based total intravenous anesthesia was initiated at 12 mg/kg/min or 2.5 mcg/mL via target-controlled infusion, respectively, along with remifentanil. After confirming the loss of consciousness, the administration rate was adjusted using electroencephalographic monitoring. The primary outcome was the rate of arterial hypotension, defined as a mean arterial pressure < 60 mmHg, from anesthesia induction until the beginning of the surgical incision. The total doses of ephedrine and phenylephrine were also assessed. Results: During anesthesia induction, the arterial hypotension rates were 11.9% and 21.6% in the remimazolam and propofol groups, respectively (P = 0.01). The total dose of ephedrine was higher in the propofol group (14.4 mg) than in the remimazolam group (1.6 mg) (P < 0.001); however, the total dose of phenylephrine was not significantly different between the two groups (propofol 0.31 mg vs. remimazolam: 0.17 mg, P = 0.10). Conclusion: Remimazolam-based total intravenous anesthesia resulted in a lower hypotension rate than propofol-based total intravenous anesthesia during induction in patients undergoing TAVR. Remimazolam-based total intravenous anesthesia can be used safely during anesthetic induction in patients with severe aortic stenosis. [ABSTRACT FROM AUTHOR]

The development of BCR::ABL1-targeting tyrosine kinase inhibitors (TKIs) has improved the prognosis of patients with chronic myeloid leukemia (CML). However, resistance to ABL TKIs can develop in CML patients due to BCR::ABL1 point mutations and CML leukemia stem cell (LSC). Aurora kinases are essential kinases for cell division and regulate mitosis, especially the process of chromosomal segregation. Aurora kinase members also promote cancer cell survival and proliferation. This study analyzed whether aurora kinases were regulated in the progression of CML. It also evaluated the efficacy of the ABL TKI asciminib and the aurora kinase inhibitor LY3295668. The expressions of AURKA and AURKB were higher in the CML cells compared with normal cells using a public database (GSE100026). Asciminib or LY3295668 alone inhibited CML cells after 72 h, and cellular cytotoxicity was increased. The combined use of Asciminib and LY3295668 increased superior efficacy compared with either drug alone. Colony formation was reduced by cotreatment with asciminib and LY3295668. In the cell-cycle analyses, LY3295668 induced G2/M arrest. Cell populations in the sub-G1 phase were observed when cotreating with asciminib and LY3295668. The combination treatment also changed the mitochondrial membrane potential. In addition, AURKA shRNA transfectant cells had increased asciminib sensitivity. Combining asciminib and aurora kinase inhibition enhanced the efficacy and is proposed as a new therapeutic option for patients with CML. These findings have clinical implications for a potential novel therapeutic strategy for CML patients. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to clarify associations between subacute hematoma on placental magnetic resonance imaging (MRI), antenatal bleeding, and preterm deliveries in patients with placenta previa (PP) without placenta accreta spectrum (PAS). Materials and methods: This retrospective study investigated 78 consecutive patients with PP (median age, 34.5 years; interquartile range [IQR], 31–37 years) who underwent placental MRI in the third trimester. Patients with PAS detected intraoperatively or pathologically were excluded. Two radiologists evaluated the presence of subacute hematomas and their locations on placental MRI. We examined associations between presence of subacute hematoma and antenatal bleeding, emergency cesarean section (CS), hysterectomy, gestational age (GA) at delivery, birth weight, and amount of blood loss at CS. We also examined the association between perinatal outcome and subacute hematoma location: marginal, retro-placental, or intra-placental. Inter-observer agreement for the detection of subacute hematoma was calculated using kappa analysis. Results: Subacute hematomas were identified on MRI in 39 of the 78 patients (50.0%). Antenatal bleeding and emergency CS were more prevalent in patients with subacute hematoma on MRI (20 patients [51.3%] and 18 patients [46.2%], respectively) than in patients without (7 patients [17.9%], Fisher's exact test, p = 0.004 and 7 patients [17.9%], p = 0.014, respectively). GA at delivery was significantly lower in patients with subacute hematoma (median 36w3d, IQR 35w4d–37w1d) than in patients without (median 37w1d, IQR 36w4d–37w2d; Mann–Whitney test: p = 0.048). Marginal hematoma was significantly associated with antenatal bleeding and emergency CS. Inter-observer agreement for the presence of subacute hematoma was moderate (κ = 0.573). Conclusion: Subacute hematoma on placental MRI was associated with antenatal bleeding, emergency CS and shorter GA at delivery in patients with PP. Marginal hematoma was also associated with antenatal bleeding and emergency CS. Placental MRI appears useful for predicting antenatal bleeding and preterm delivery in patients with PP. [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]

Purpose of Review: Fungal diseases disproportionately affect certain demographic populations, but few studies have thoroughly investigated the drivers of those disparities. We summarize data sources that can be considered to explore potential associations between fungal diseases and social determinants of health in the United States. Recent Findings: Sociodemographic disparities are apparent in fungal diseases, and social determinants of health (e.g., income, living conditions, and healthcare access) may be associated with increased risk of infection, severe disease, and poor health outcomes. Summary: Numerous data sources are available in the United States to analyze the potential association between fungal diseases and underlying social determinants of health. Each source has benefits and limitations that should be considered in the development of analysis plans. Inherent challenges to all fungal disease data (e.g., underdiagnosis, underreporting, and inability to detect people who do not seek medical care) should be noted and accounted for in interpretation of results. [ABSTRACT FROM AUTHOR]

Adolescent idiopathic scoliosis (AIS) affects approximately 3% of the global population. Recent studies have drawn attention to abnormalities in the dynamics of the CSF as potential contributors. This research aims to employ the Time-Spatial Labeling Inversion Pulse (Time-SLIP) MRI to assess and analyze cerebrospinal fluid (CSF) dynamics in AIS patients. 101 AIS patients underwent Time-SLIP MRI. Images were taken at the mid-cervical and craniocervical junction regions. The sum of the maximum movement distances of CSF on the ventral and dorsal sides of the spinal canal within a single timeframe was defined and measured as Travel Distance (TD). Correlations between TD, age, Cobb angle, and Risser grade were analyzed. TD comparisons were made across Lenke classifications. TD for all patients was a weak correlation with the Cobb angle (r = − 0.16). Comparing TD between Lenke type 1 and 5, type 5 patients display significantly shorter TD (p < 0.05). In Risser5 patients with Lenke type 5 showed a significant negative correlation between Cobb angle and TD (r = − 0.44). Lenke type 5 patients had significantly shorter CSF TD compared to type1, correlating with worsening Cobb angles. Further analysis and exploration are required to understand the mechanism of onset and progression. [ABSTRACT FROM AUTHOR]

Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC), a rare and complex neurological disorder, is predominantly observed in the Western Pacific islands, including regions of Japan, Guam, and Papua. This enigmatic condition continues to capture medical attention due to affected patients displaying symptoms that parallel those seen in either classical amyotrophic lateral sclerosis (ALS) or Parkinson's disease (PD). Distinctly, postmortem examinations of the brains of affected individuals have shown the presence of α-synuclein aggregates and TDP-43, which are hallmarks of PD and classical ALS, respectively. These observations are further complicated by the detection of phosphorylated tau, accentuating the multifaceted proteinopathic nature of ALS/PDC. The etiological foundations of this disease remain undetermined, and genetic investigations have yet to provide conclusive answers. However, emerging evidence has implicated the contribution of astrocytes, pivotal cells for maintaining brain health, to neurodegenerative onset, and likely to play a significant role in the pathogenesis of ALS/PDC. Leveraging advanced induced pluripotent stem cell technology, our team cultivated multiple astrocyte lines to further investigate the Japanese variant of ALS/PDC (Kii ALS/PDC). CHCHD2 emerged as a significantly dysregulated gene when disease astrocytes were compared to healthy controls. Our analyses also revealed imbalances in the activation of specific pathways: those associated with astrocytic cilium dysfunction, known to be involved in neurodegeneration, and those related to major neurological disorders, including classical ALS and PD. Further in-depth examinations revealed abnormalities in the mitochondrial morphology and metabolic processes of the affected astrocytes. A particularly striking observation was the reduced expression of CHCHD2 in the spinal cord, motor cortex, and oculomotor nuclei of patients with Kii ALS/PDC. In summary, our findings suggest a potential reduction in the support Kii ALS/PDC astrocytes provide to neurons, emphasizing the need to explore the role of CHCHD2 in maintaining mitochondrial health and its implications for the disease. [ABSTRACT FROM AUTHOR]

In chronic stages of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalitis (EAE), connexin (Cx)43 gap junction channel proteins are overexpressed because of astrogliosis. To elucidate the role of increased Cx43, the central nervous system (CNS)-permeable Cx blocker INI-0602 was therapeutically administered. C57BL6 mice with chronic EAE initiated by MOG35-55 received INI-0602 (40 mg/kg) or saline intraperitoneally every other day from days post-immunization (dpi) 17–50. Primary astroglia were employed to observe calcein efflux responses. In INI-0602-treated mice, EAE clinical signs improved significantly in the chronic phase, with reduced demyelination and decreased CD3+ T cells, Iba-1+ and F4/80+ microglia/macrophages, and C3+GFAP+ reactive astroglia infiltration in spinal cord lesions. Flow cytometry analysis of CD4+ T cells from CNS tissues revealed significantly reduced Th17 and Th17/Th1 cells (dpi 24) and Th1 cells (dpi 50). Multiplex array of cerebrospinal fluid showed significantly suppressed IL-6 and significantly increased IL-10 on dpi 24 in INI-0602-treated mice, and significantly suppressed IFN-γ and MCP-1 on dpi 50 in the same group. In vitro INI-0602 treatment inhibited ATP-induced calcium propagations of Cx43+/+ astroglial cells to similar levels of those of Cx43−/− cells. Astroglial Cx43 hemichannels represent a novel therapeutic target for chronic EAE and MS. [ABSTRACT FROM AUTHOR]

A nonvolatile optical phase shifter is a critical component for enabling the fabrication of programmable photonic integrated circuits on a Si photonics platform, facilitating communication, computing, and sensing. Although ferroelectric materials such as BaTiO3 offer nonvolatile optical phase shift capabilities, their compatibility with complementary metal-oxide-semiconductor fabs is limited. Hf0.5Zr0.5O2 is an emerging ferroelectric material, which exhibits complementary metal-oxide-semiconductor compatibility. Although extensively studied for ferroelectric transistors and memories, its application to photonics remains relatively unexplored. Here, we show the optical phase shift induced by ferroelectric Hf0.5Zr0.5O2. We observed a negative change in refractive index at a 1.55 μm wavelength in a pristine device regardless of the direction of the applied electric field. The nonvolatile phase shift was only observed once in a pristine device. This non-reversible phase shift can be attributed to the spontaneous polarization within the Hf0.5Zr0.5O2 film along the external electric field. The authors present nonvolatile optical phase shift induced by ferroelectric hafnium zirconium oxide deposited on a SiN waveguide. This finding paves the way for largescale programmable photonic circuits for communication, computing, and sensing. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess whether short repetition time (TR) diffusion-weighted imaging (DWI) could improve diffusion contrast in patients with prostate cancer (PCa) compared with long TR (conventional) reference standard DWI. Materials and methods: Our Institutional Review Board approved this retrospective study and waived the need for informed consent. Twenty-five patients with suspected PCa underwent multiparametric magnetic resonance imaging (mp-MRI) using a 3.0-T system. DWI was performed with TR of 1850 ms (short) and 6000 ms (long) with b-values of 0, 1000, and 2000s/mm2. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), visual score, apparent diffusion coefficient (ADC), and diagnostic performance were compared between short and long TR DWI for both b-values. The statistical tests included paired t-test for SNR and CNR; Wilcoxon signed-rank test for VA; Pearson's correlation and Bland–Altman plot analysis for ADC; and McNemar test and receiver operating characteristic analysis and Delong test for diagnostic performance. Results: Regarding b1000, CNR and visual score were significantly higher in short TR compared with long TR (P =.003 and P =.002, respectively), without significant difference in SNR (P =.21). Considering b2000, there was no significant difference in visual score between short and long TR (P =.07). However, SNR and CNR in long TR were higher (P =.01 and P =.04, respectively). ADC showed significant correlations, without apparent bias for ADC between short and long TR for both b-values. For diagnostic performance of DWI between short and long TR for both b-values, one out of five readers noted a significant difference, with the short TR for both b-values demonstrating superior performance. Conclusions: Our data showed that the short TR DWI1000 may provide better image quality than did the long TR DWI1000 and may improve visualization and diagnostic performance of PCa for readers. [ABSTRACT FROM AUTHOR]

Purpose: We compared the clinical features of patients with biliary atresia (BA) associated with a bleeding tendency (BT) at the time of the diagnosis with those of patients without a bleeding tendency (NBT). Methods: The patients' background characteristics, age in days at the first visit, Kasai portoenterostomy (KPE), and postoperative course were retrospectively analyzed. Results: Nine of the 93 BA patients (9.7%) showed a BT, including 7 with intracranial hemorrhaging (ICH), 1 with gastrointestinal bleeding, and 1 with a prothrombin time (PT) of 0%. The age at the first visit was 62 ± 12 days old for BT patients and 53 ± 27 days old for NBT patients (p = 0.4); the age at KPE was 77 ± 9 days old for BT patients and 65 ± 24 days old for NBT patients (p = 0.2); the time from the first visit to surgery was 13 ± 7 days for BT patients and 11 ± 10 days for NBT patients (p = 0.5); and the native liver survival rate was 56% for BT patients and 58% for NBT patients (p = 1), with no significant difference in any of the parameters. The neurological outcomes of survivors of ICH were favorable. Conclusions: Appropriate BT correction allowed early KPE even after ICH, resulting in native liver survival rates comparable to those of NBT patients without significant neurological complications. [ABSTRACT FROM AUTHOR]

We hypothesized that lactic acid bacteria (LAB) present in sediments at aquaculture sites can be employed as an indicator for the early prediction of deterioration, as the concentration of organic acids controls hydrogen sulfide production via sulfate-reducing bacteria. We selected two aquaculture sites with different acid volatile sulfide (AVS-S) values, St. OJ (average AVS-S = 0.24 mg S/g dry mud) and St. UM (average AVS-S = 1.16 mg S/g dry mud), which were less and critically deteriorated, respectively, and examined our hypothesis by performing a 3-year-long survey in Tanabe Bay, Wakayama Prefecture, Japan. In St. UM, the bacterial community showed positive correlations with AVS-S values and water contents. With AVS-S accumulation at the site, the abundances of LAB decreased below the detection limit, suggesting that LAB viable counts may be unsuitable for predicting early deterioration at sites with severe AVS-S accumulation. In St. OJ, the LAB viable counts, organic acid content, and AVS-S values increased after the beginning of sea bream aquaculture, and the bacterial community showed high correlations with the LAB counts, succinic and total organic acid concentrations, and the abundance of the class Bacilli. These on-site experiments indicated that LAB counts can be a reasonable indicator for evaluating deterioration in aquaculture sites. [ABSTRACT FROM AUTHOR]

Purpose: To identify the risk factors for perioperative complications to prevent perioperative complications after complete ipsilateral upper urinary stone removal using flexible ureterorenoscopy. Materials and methods: We retrospectively examined 111 patients who underwent flexible ureterorenoscopy for ipsilateral renal stones with a diameter ≥ 5 mm at the same time as ureterorenoscopy for ureteric stones. The flexible ureterorenoscopy procedures were performed following the fragmentation technique. Patients who experienced (complication group) and did not experience (non-complication group) perioperative complications were compared. The complication group included 33 patients with Clavien–Dindo classification scores of I, II, III, or IV and/or those with a body temperature of > 37.5 ℃ during hospitalization. Results: The overall stone volume, stone-free rate and procedure duration were 1.71 mL, 96.4% and 77 min, respectively. The rate of perioperative complications was 29.7% (grade 1, 2 and 3 was 23.4%, 5.4% and 0.9%, respectively). Severe complications (Clavien–Dindo grade 4) were not observed. Multivariable analysis revealed that ureteral stone volume and female patients were independent predictors of perioperative complications after flexible ureterorenoscopy (p = 0.015 and 0.017, respectively). Conclusions: This study showed that ureteral stone volume and female gender have the possibility to increase perioperative complications. These preliminary data help to select for patients who are at low risk of complications. Therefore, in these selected patients, complete ipsilateral upper urinary tract stone removal using flexible ureterorenoscopy may reduce the recurrence of urolithiasis without increasing perioperative complications. [ABSTRACT FROM AUTHOR]

Backgrounds: Cycle-consistent generative adversarial network (CycleGAN) is a deep neural network model that performs image-to-image translations. We generated virtual indigo carmine (IC) chromoendoscopy images of gastric neoplasms using CycleGAN and compared their diagnostic performance with that of white light endoscopy (WLE). Methods: WLE and IC images of 176 patients with gastric neoplasms who underwent endoscopic resection were obtained. We used 1,633 images (911 WLE and 722 IC) of 146 cases in the training dataset to develop virtual IC images using CycleGAN. The remaining 30 WLE images were translated into 30 virtual IC images using the trained CycleGAN and used for validation. The lesion borders were evaluated by 118 endoscopists from 22 institutions using the 60 paired virtual IC and WLE images. The lesion area concordance rate and successful whole-lesion diagnosis were compared. Results: The lesion area concordance rate based on the pathological diagnosis in virtual IC was lower than in WLE (44.1% vs. 48.5%, p < 0.01). The successful whole-lesion diagnosis was higher in the virtual IC than in WLE images; however, the difference was insignificant (28.2% vs. 26.4%, p = 0.11). Conversely, subgroup analyses revealed a significantly higher diagnosis in virtual IC than in WLE for depressed morphology (41.9% vs. 36.9%, p = 0.02), differentiated histology (27.6% vs. 24.8%, p = 0.02), smaller lesion size (42.3% vs. 38.3%, p = 0.01), and assessed by expert endoscopists (27.3% vs. 23.6%, p = 0.03). Conclusions: The diagnostic ability of virtual IC was higher for some lesions, but not completely superior to that of WLE. Adjustments are required to improve the imaging system's performance. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is an arrhythmic disease. Prediction of AF development in healthy individuals is important before serious complications occur. We aimed to develop a risk prediction score for future AF using participants' data, including electrocardiogram (ECG) measurements and information such as age and sex. We included 88,907 Japanese participants, aged 30–69 years, who were randomly assigned to derivation and validation cohorts in a ratio of 1:1. We performed multivariate logistic regression analysis and obtained the standardised beta coefficient of relevant factors and assigned scores to them. We created a score based on prognostic factors for AF to predict its occurrence after five years and applied it to validation cohorts to assess its reproducibility. The risk score ranged from 0 to 17, consisting of age, sex, PR prolongation, QT corrected for heart rate prolongation, left ventricular hypertrophy, premature atrial contraction, and left axis deviation. The area under the curve was 0.75 for the derivation cohort and 0.73 for the validation cohort. The incidence of new-onset AF reached over 2% at 10 points of the risk score in both cohorts. Thus, in this study, we showed the possibility of predicting new-onset AF using ECG findings and simple information. [ABSTRACT FROM AUTHOR]

Background: Guanfacine is an alpha-2 adrenergic agonist that decreases norepinephrine release and sympathetic outflow. With the increased use of guanfacine for attention-deficit hyperactivity disorder (ADHD), reports of guanfacine poisoning have also risen. Case presentation: A 15-year-old male (height: 170 cm, weight: 48 kg), who was taking 2 mg/day of guanfacine for ADHD, was brought to our emergency department after ingesting 40 tablets of guanfacine due to poor exam results. He presented with impaired consciousness and sinus bradycardia on an electrocardiogram (ECG), leading to diagnosis of guanfacine poisoning. Gastric lavage (5 L) was performed, and activated charcoal was administered. Although his consciousness gradually recovered, he developed ST-segment elevation on the ECG. Despite the absence of chest pain and elevated myocardial enzymes, coronary artery stenosis was not observed on coronary artery computed tomography. As his blood guanfacine level decreased, his ECG returned to normal. Conclusions: This case highlights the need for careful monitoring of guanfacine poisoning patients due to the potential for various cardiovascular events. [ABSTRACT FROM AUTHOR]

Lumbar spinal alignment is crucial for spine biomechanics and is linked to various spinal pathologies. However, limited research has explored gender-specific differences using CT scans. The objective was to evaluate and compare lumbar spinal alignment between standing and sitting CT in healthy individuals, focusing on gender differences. 24 young and 25 elderly males (M) and females (F) underwent standing and sitting CT scans to assess lumbar spinal alignment. Parameters measured and compared between genders included lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), lordotic angle (LA), foraminal height (FH), and bony boundary area (BBA). Females showed significantly larger changes in SS and PT when transitioning from standing to sitting (p =.044, p =.038). A notable gender difference was also observed in the L4-S LA among the elderly, with females showing a significantly larger decrease in lordotic angle compared to males (− 14.1° vs. − 9.2°, p =.039*). Females consistently exhibited larger FH and BBA values, particularly in lower lumbar segments, which was more prominent in the elderly group (M vs. F: L4/5 BBA 80.1 mm2 [46.3, 97.8] vs. 109.7 mm2 [74.4, 121.3], p =.019 in sitting). These findings underline distinct gender-related variations in lumbar alignment and flexibility, with a focus on noteworthy changes in BBA and FH in females. Gender differences in lumbar spinal alignment were evident, with females displaying greater pelvic and sacral mobility. Considering gender-specific characteristics is crucial for assessing spinal alignment and understanding spinal pathologies. These findings contribute to our understanding of lumbar spinal alignment and have implications for gender-specific spinal conditions and treatments. [ABSTRACT FROM AUTHOR]

Background: We investigated the prognostic impact of osteosarcopenia, defined as the combination of osteopenia and sarcopenia, in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma (PDAC). Methods: The relationship of osteosarcopenia with disease-free survival and overall survival was analyzed in 183 patients who underwent elective pancreatic resection for PDAC. Computed tomography was used to measure the pixel density in the midvertebral core of the 11th thoracic vertebra for evaluation of osteopenia and in the psoas muscle area of the 3rd lumbar vertebra for evaluation of sarcopenia. Osteosarcopenia was defined as the simultaneous presence of both osteopenia and sarcopenia. The study employed a retrospective design to examine the relationship between osteosarcopenia and survival outcomes. Results: Osteosarcopenia was identified in 61 (33%) patients. In the univariate analysis, disease-free survival was significantly worse in patients with male sex (p = 0.031), pathological stage ≥ III PDAC (p = 0.001), NLR, ≥ 2.71 (p = 0.041), sarcopenia (p = 0.027), osteopenia (p = 0.001), and osteosarcopenia (p < 0.001), and overall survival was significantly worse in patients with male sex (p = 0.001), pathological stage ≥ III PDAC (p = 0.001), distal pancreatectomy (p = 0.025), sarcopenia (p = 0.003), osteopenia (p < 0.001), and osteosarcopenia (p < 0.001). In the multivariate analysis, the independent predictors of disease-free survival were osteosarcopenia (p < 0.001) and pathological stage ≥ III PDAC (p = 0.002), and the independent predictors of overall survival were osteosarcopenia (p < 0.001), male sex (p = 0.006) and pathological stage ≥ III PDAC (p = 0.001). Conclusion: Osteosarcopenia has an adverse prognostic impact on long-term outcomes in patients undergoing pancreatic resection for PDAC. [ABSTRACT FROM AUTHOR]