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Abstract Tissue factor (TF) is a cell surface protein that plays a role in blood clotting but is also commonly expressed in many cancers. Recent research implicated TF in cancer proliferation, metastasis, angiogenesis, and immune escape. Therefore, TF can be considered a viable therapeutic target against cancer. Herein, we developed and tested a TF-targeted near-infrared photoimmunotherapy (NIR-PIT) as a potential treatment for several types of cancer. Tisotumab, a TF antibody, was conjugated to IR700. The efficacy of TF-targeted NIR-PIT was investigated using multiple cancer cell lines (A431; epidermoid carcinoma, HPAF-II; pancreatic adenocarcinoma, HSC-2; oral carcinoma, HT1376-luc; bladder carcinoma, MDAMB231; breast adenocarcinoma, and SKOV3-luc; ovarian serous cystadenocarcinoma) in vitro. In vivo, the efficacy of TF-targeted NIR-PIT was evaluated in HPAF-II and A431 xenograft mouse models. Pathologic changes in these tumors after NIR-PIT were evaluated in these tumor models. All cancer lines demonstrated TF expression in vitro and in vivo. Additionally, TF expression was documented to localize to cancer cells in tumors. In vitro, TF-targeted NIR-PIT caused cell death in a light dose-dependent manner. In vivo, TF-targeted NIR-PIT suppressed tumor growth and improved survival rates compared to controls. Furthermore, in vivo NIR-PIT showed histological signs of cancer cell damage, such as cytoplasmic vacuolation, nuclear dysmorphism, and extracellular leakage of LDHA consistent with cell death. In conclusion, TF-targeted NIR-PIT holds promise as a treatment for multiple cancer models expressing TF, spanning multiple cancer types.

Abstract Rapid Diagnostic Tests (RDTs) have been an important diagnostic tool for detecting P. falciparum malaria in resource-limited settings. Most tests are designed to detect the Histidine-rich Protein 2 (HRP2). Parasites lacking pfhrp2 and its homologous pfhrp3 have been reported in several regions, with prevalence reaching 100% in certain areas. To better characterize P. falciparum isolates circulating in the Brazil-Venezuela-Guyana tri-border region, we performed a comprehensive analysis of 365 samples collected between 2016 and 2018. Molecular and immunological methods were employed to detect HRP2 and confirm pfhrp2/3 deletions. Our findings point to a low prevalence (1%) of pfhrp2-deleted parasites confirmed by the lack of HRP2 detection. Among false-negative HRP2-RDT tests (6%), most were attributed to low parasite densities. A merozoite surface protein 2 (msp2)-based intra-host diversity analysis suggested overall low genetic diversity. The pattern of HRP2 sequences resembled that has been previously described in areas along the Brazil and French Guiana border. In conclusion, we have found a low prevalence of pfhrp2-deleted parasites in the north-central Guiana Shield, which contrasts with the findings reported at the Peru border. Continued surveys are necessary to monitor the prevalence of pfhrp2 deletion in this area characterized by a high number of cross-border malaria cases.

Abstract Background Protothecosis in dogs is a rare, yet emerging disease, distinguished by its often‐aggressive clinical course and high fatality rate. Our study was conducted to enhance treatment protocols for affected dogs by better understanding the genetic diversity and drug resistance patterns of Prototheca species. Objectives To identify species and drug susceptibility profiles of an international collection of 28 Prototheca strains isolated from cases of protothecosis in dogs. Animals None. Methods Retrospective study. Species‐level identification was made for isolates from 28 dogs in 6 countries by molecular typing with the partial cytb gene as a marker. For the determination of minimum inhibitory concentrations (MICs) and minimum algicidal concentrations (MACs), the Clinical Laboratory Standards Institute (CLSI) protocol (M27‐A3) was used. Results Prototheca bovis was the most prevalent species, accounting for 75% (21/28) of the cases, followed by P. wickerhamii (18%; 5/28) and P. ciferrii (7%; 2/28). Of the 6 drugs tested, efinaconazole (EFZ) was the most potent in vitro, with its median MIC and MAC values equal to 0.125 mg/L. The lowest activity was found for fluconazole (FLU), with MIC and MAC medians of 48 mg/L and 64 mg/L, respectively. Conclusions and Clinical Importance Our study identifies P. bovis as the species that most frequently causes protothecosis in dogs, which suggests the possibility of cross‐species infection from other animals, especially cows. Additionally, it indicates that EFZ could be used in the treatment of infection in the colon.

This paper explores the applicability of bicycle-inspired balance control in a quadruped robot model. Bicycles maintain stability and change direction by intuitively steering the handle, which induces yaw motion in the body frame and generates an inertial effect to support balance. Inspired by this balancing strategy, we implemented a similar mechanism in a quadruped robot model, introducing a yaw trunk joint analogous to a bicycle’s steering handle. Simulation results demonstrate that the proposed model achieves stable high-speed locomotion with robustness against external disturbances and maneuverability that allows directional changes with only slight speed reduction. These findings suggest that utilizing centrifugal force plays a critical role in agile locomotion, aligning with the movement strategies of cursorial animals. This study underscores the potential of bicycle balance control as an effective and straightforward control approach for enhancing the agility and stability of quadruped robots as well as potentially offering insights into animal motor control mechanisms for agile locomotion.

BackgroundNivolumab paved a new way in the treatment of patients with recurrent or metastatic (RM) head and neck squamous cell carcinoma (RM-HNSCC). However, the limited rates of long-term survivors (< 20%) demand a robust prognostic biomarker. This nationwide multi-centric prospective study aimed to identify a plasma exosome (PEX) mRNA signature, which serves as a companion diagnostic of nivolumab and provides a biological clue to develop effective therapies for a majority of non-survivors.MethodsPre-treatment plasmas (N = 104) of RM-HNSCC patients were subjected to comprehensive PEX mRNA analyses for prognostic marker discovery and validation. In parallel, paired treatment-naïve tumor and plasma samples (N = 20) were assayed to elucidate biological implications of the PEX mRNA signature.ResultsAssays for pre-treatment blood samples (N = 104) demonstrated that a combination of 6 candidate PEX mRNAs plus neutrophil-to-lymphocyte ratio precisely distinguished non-survivors from >2-year survivors (2-year OS; 0% vs 57.7%; P = 0.000124) with a high hazard ratio of 2.878 (95% CI 1.639-5.055; P = 0.0002348). Parallel biological assays demonstrated that in the paired treatment-naïve HNSCC tumor and plasma samples (N = 20), PEX HLA-E mRNA (a non-survivor-predicting marker) was positively corelated with overexpression of HLA-E protein (P = 0.0191) and the dense population of tumor-infiltrating NK cells (P = 0.024) in the corresponding tumor, suggesting that the HLA-E-NKG2A immune checkpoint may inhibit the antitumor effect of PD-1blockade.ConclusionThe PEX mRNA signature could be useful as a companion diagnostic of nivolumab. The combination of an anti-NKG2A antibody (i.e., monalizumab) and nivolumab may serve as a treatment option for non-survivors predicted by a RT-qPCR-based pre-treatment measurement of PEX mRNAs.

In recent decades, many fungi have emerged as major causes of disease in marine mammals. This study reports on the detection of filamentous fungi in the subcutaneous tissue and wound surface on the tail fin of a managed bottlenose dolphin (Tursiops truncatus) emaciated due to severe digestive problems. Immunosuppression by chronic diseases and starvation decreased resistance against opportunistic infections. Sequencing analysis revealed that the fungi on the wound surface were Fusarium oxysporum, and antifungal susceptibility testing was performed. In the subcutaneous tissue, dematiaceous fungi were identified using histopathological examination. Combination antifungal treatment with voriconazole and terbinafine and surgical resection were performed, in addition to daily debridement with polyaminopropyl biguanide (PHMB) and betaine. Hematological examination revealed a reduction in inflammatory markers after antifungal treatment and surgical resection of necrotic tissue on the edge of the tail fin. The co-administration of synergistic agents voriconazole and terbinafine, in conjunction with surgical debridement, successfully eliminated pheohyphomycosis and fusariomycosis in the bottlenose dolphin. Wound healing was achieved using systematic antifungals and daily debridement with PHMB and betaine. This is the first report of successful treatment of pheohyphomycosis and fusariomycosis in a bottlenose dolphin using voriconazole and terbinafine combination therapy and surgical resection.

We report the first detection of a magnetic discontinuity in the upper solar chromosphere associated with a coronal loop brightening. Our findings are based on novel observations obtained by the Chromospheric LAyer SpectroPolarimeter (CLASP2.1) suborbital space experiment. During its short 6 minute flight, CLASP2.1 successfully obtained spectropolarimetric data across the Mg ii h and k lines, which allowed us to map the longitudinal magnetic field at multiple heights in the chromosphere of a solar active region. During our observation, we found a coronal loop brightening that was intermittently and recurrently heated. The temperature of the brightening plasma is above 2.5 MK, which is higher than the ambient temperature, and no corresponding brightening is detected in the images of the photosphere and lower chromosphere. The notable finding of our study is that the coronal loop brightening of interest is observed across a region where the magnetic field polarity changes abruptly in the upper chromosphere. Our results provide observational evidence that the heating mechanism of the coronal loop brightening is consistent with magnetic reconnection in the upper solar chromosphere.

Background: Nivolumab paved a new way in the treatment of patients with recurrent or metastatic (RM) head and neck squamous cell carcinoma (RM-HNSCC). However, the limited rates of long-term survivors (< 20%) demand a robust prognostic biomarker. This nationwide multi-centric prospective study aimed to identify a plasma exosome (PEX) mRNA signature, which serves as a companion diagnostic of nivolumab and provides a biological clue to develop effective therapies for a majority of non-survivors. Methods: Pre-treatment plasmas (N = 104) of RM-HNSCC patients were subjected to comprehensive PEX mRNA analyses for prognostic marker discovery and validation. In parallel, paired treatment-naïve tumor and plasma samples (N = 20) were assayed to elucidate biological implications of the PEX mRNA signature. Results: Assays for pre-treatment blood samples (N = 104) demonstrated that a combination of 6 candidate PEX mRNAs plus neutrophil-to-lymphocyte ratio precisely distinguished non-survivors from >2-year survivors (2-year OS; 0% vs 57.7%; P = 0.000124) with a high hazard ratio of 2.878 (95% CI 1.639-5.055; P = 0.0002348). Parallel biological assays demonstrated that in the paired treatment-naïve HNSCC tumor and plasma samples (N = 20), PEX HLA-E mRNA (a non-survivor-predicting marker) was positively corelated with overexpression of HLA-E protein (P = 0.0191) and the dense population of tumor-infiltrating NK cells (P = 0.024) in the corresponding tumor, suggesting that the HLA-E-NKG2A immune checkpoint may inhibit the antitumor effect of PD-1blockade. Conclusion: The PEX mRNA signature could be useful as a companion diagnostic of nivolumab. The combination of an anti-NKG2A antibody (i.e., monalizumab) and nivolumab may serve as a treatment option for non-survivors predicted by a RT-qPCR-based pre-treatment measurement of PEX mRNAs. [ABSTRACT FROM AUTHOR]

This paper explores the applicability of bicycle-inspired balance control in a quadruped robot model. Bicycles maintain stability and change direction by intuitively steering the handle, which induces yaw motion in the body frame and generates an inertial effect to support balance. Inspired by this balancing strategy, we implemented a similar mechanism in a quadruped robot model, introducing a yaw trunk joint analogous to a bicycle's steering handle. Simulation results demonstrate that the proposed model achieves stable high-speed locomotion with robustness against external disturbances and maneuverability that allows directional changes with only slight speed reduction. These findings suggest that utilizing centrifugal force plays a critical role in agile locomotion, aligning with the movement strategies of cursorial animals. This study underscores the potential of bicycle balance control as an effective and straightforward control approach for enhancing the agility and stability of quadruped robots as well as potentially offering insights into animal motor control mechanisms for agile locomotion. [ABSTRACT FROM AUTHOR]

A detailed understanding of the adhesive properties of a carbon nanotube (CNT)-based gecko tape with respect to microscale particles is necessary for its practical application as a supporting medium for specific solid materials. We obtained the force curves of vertically aligned CNTs (VACNTs) for individual microparticles of various diameters using atomic force microscopy and evaluated their adhesion force and adhesion length. The measured adhesive force followed the apparent contact area with increasing embedding depth and was size-dependent at scales of several tens of micrometers. The adhesive forces measured for a 20 µm-diameter bead was significantly higher than those for larger particles, which may be related to inclination of the adherent surface against the VACNT tape surface. The adhesion length depended on the type of the CNTs comprising the VACNT, rather than on the bead size. The evaluation of VACNTs with different morphologies suggested that the flexibility of the individual CNTs and the density of the CNT – CNT interconnections in the VACNTs were important factors for obtaining the true contact area to realize better adhesion of micrometer-sized particles. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the frequency and predictive factors of the development of postoperative pectus excavatum and scoliosis in children who underwent surgery for cystic lung disease. Methods: This study examined patients who underwent surgery for cystic lung disease (open and thoracoscopic) between July 2000 and December 2018 with a > 3-year follow-up period. Lesion size, surgical outcomes, and subsequent musculoskeletal complications were compared between the open surgery and thoracoscopic surgery groups. Univariate and multivariate analyses were performed to identify predictive factors. Results: Overall, 90 patients (19 and 71 patients in the open and thoracoscopic groups, respectively) were included in this study. There was no significant difference in the incidence of pectus excavatum or scoliosis between open and thoracoscopic surgery; however, Haller's index and Cobb angle were significantly higher in the open surgery group. In the univariate analysis, neonatal surgery and lesion size were substantial predictors of musculoskeletal malformations. Conclusion: Postoperative musculoskeletal deformities emerge after surgical treatment for cystic lung disease, with thoracoscopic surgery showing advantages in selected dimensions. Neonatal surgery and lesion size are pivotal prognostic factors for musculoskeletal complications. Further corroborative multicenter studies are imperative to substantiate these findings and foster enhanced patient outcomes. [ABSTRACT FROM AUTHOR]

ABSTRACT Establishment of a suitable animal model to evaluate sustained release (SR) formulations is very important because it reduces the development time of SR formulations. Beagle dogs are often used to evaluate prototype formulations since they can be directly administered powder, such as drug substance. However, the physiological condition of dogs is very different to that of humans. Therefore, the benefits of utilizing beagle dogs for the evaluation of modified release formulations such as sustained release formulations and enteric‐coated formulations are doubtful. To clarify the best animal and/or experimental technique for the evaluation of modified release formulations, we investigated dipyridamole pharmacokinetics from prototype sustained release granules by utilizing beagle dogs, propantheline bromide‐treated (PBT) beagle dogs, and miniature pigs. In normal dogs, the intestinal absorption and sustained release effect of dipyridamole decreased in the 20 mg sustained release granule. However, in PBT dogs, a sustained release effect was observed in the 45 mg sustained release granule, and its bioavailability was also maintained. Accordingly, PBT dogs could be the best to evaluate sustained release formulations such as tablets and granules, and the use of miniature pigs might be better to evaluate granules with equal to or less than 1 mm diameter. [ABSTRACT FROM AUTHOR]

Microbial indigo reduction is a key reaction in indigo dyeing; however, the mechanism of the interaction with indigo remains unclear. We hypothesized that lignin is a candidate substance that supports this interaction. The addition of lignin effectively enhanced the indigo reduction. The reducing activity of indigo correlated with the particle size after the addition of lignin. [ABSTRACT FROM AUTHOR]

Intracellular calcium ion regulation drives skeletal muscle adaptations posteccentric contractions: key role for ryanodine receptors. Eccentric contractions (ECC) induce excessive intracellular calcium ion (Ca2+) accumulation and muscle structural damage in localized regions of the muscle fibers. In this investigation, we present the novel hypothesis that the ryanodine receptor (RyR) plays a central role in evoking a Ca2+ dynamics profile that is markedly distinguishable from other muscle adaptive responses. [ABSTRACT FROM AUTHOR]

In recent decades, many fungi have emerged as major causes of disease in marine mammals. This study reports on the detection of filamentous fungi in the subcutaneous tissue and wound surface on the tail fin of a managed bottlenose dolphin (Tursiops truncatus) emaciated due to severe digestive problems. Immunosuppression by chronic diseases and starvation decreased resistance against opportunistic infections. Sequencing analysis revealed that the fungi on the wound surface were Fusarium oxysporum, and antifungal susceptibility testing was performed. In the subcutaneous tissue, dematiaceous fungi were identified using histopathological examination. Combination antifungal treatment with voriconazole and terbinafine and surgical resection were performed, in addition to daily debridement with polyaminopropyl biguanide (PHMB) and betaine. Hematological examination revealed a reduction in inflammatory markers after antifungal treatment and surgical resection of necrotic tissue on the edge of the tail fin. The co-administration of synergistic agents voriconazole and terbinafine, in conjunction with surgical debridement, successfully eliminated pheohyphomycosis and fusariomycosis in the bottlenose dolphin. Wound healing was achieved using systematic antifungals and daily debridement with PHMB and betaine. This is the first report of successful treatment of pheohyphomycosis and fusariomycosis in a bottlenose dolphin using voriconazole and terbinafine combination therapy and surgical resection. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are effective in treating recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but only 20% of patients achieve durable responses. This study evaluated circulating tumor DNA (ctDNA) as a real-time biomarker for monitoring treatment response in HNSCC. The SHIZUKU-HN study prospectively collected and analyzed serial plasma samples (n = 27) from HNSCC patients undergoing ICIs, using Guardant360 to assess ctDNA variant allele frequency (VAF) and genetic mutations. Tumor volumes were quantified using 3D reconstruction of CT scans, and data from Japan's C-CAT database (n = 2255) provided insights into ctDNA testing in HNSCC. C-CAT data showed that ctDNA testing was underutilized, performed in only 7% of head and neck cancer cases. In SHIZUKU-HN, mean VAF significantly correlated with tumor volume (Spearman's ρ = 0.70, p = 0.001), often preceding radiographic progression. BRAF and APC mutations disappeared in partial responders, while GNAS mutations varied. EGFR and PIK3CA amplifications, detectable via ctDNA but missed in tissue biopsies, indicated emerging resistance mechanisms. The SHIZUKU-HN study demonstrates the potential of ctDNA as a dynamic biomarker in HNSCC, offering early insights into treatment efficacy and informing personalized ICI therapy. [ABSTRACT FROM AUTHOR]

Eccentric contractions (ECC) are accompanied by the accumulation of intracellular calcium ions ([Ca2+]i) and induce skeletal muscle damage. Suppressed muscle damage in repeated bouts of ECC is well characterized; however, whether it is mediated by altered Ca2+ profiles remains unknown. We tested the hypothesis that repeated ECC suppresses Ca2+ accumulation via adaptations in Ca2+ regulation. Male Wistar rats were divided into two groups: ECC single bout (ECC-SB) and repeated bout (ECC-RB). Tibialis anterior (TA) muscles were subjected to ECC (40 times, 5 sets) once (ECC-SB) or twice 14 days apart (ECC-RB). Under anesthesia, the TA muscle was loaded with Ca2+ indicator Fura 2-AM, and the 340/380 nm ratio was evaluated as [Ca2+]i. Ca2+ handling proteins were measured by Western blots. ECC induced [Ca2+]i increase in both groups, but ECC-RB evinced a markedly suppressed [Ca2+]i (Time: P < 0.01, Group: P = 0.0357). Five hours post-ECC, in contrast to the localized [Ca2+]i accumulation in ECC-SB, ECC-RB exhibited lower and more uniform [Ca2+]i (P < 0.01). In ECC-RB, mitochondria Ca2+ uniporter complex (MCU) components MCU and MICU2 were significantly increased pre-second ECC bout (P < 0.01), and both SERCA1 and MICU1 were better preserved after contractions (P < 0.01). Fourteen days after novel ECC, skeletal muscle mitochondrial Ca2+ regulating proteins were elevated. Following subsequent ECC, [Ca2+]i accumulation and muscle damage were suppressed and SERCA1 and MICU1 preserved. These findings suggest that tolerance to a subsequent ECC bout is driven, at least in part, by enhanced mitochondrial and sarcoplasmic reticulum Ca2+ regulation. NEW & NOTEWORTHY: We demonstrated a reduced [Ca2+]i profile with suppressed muscle damage after a repeated bout of ECC in vivo: the ECC-induced immediate [Ca2+]i increase was suppressed and the persistence of increased [Ca2+]i with localized accumulation was diminished after repeated ECC. This effect occurred consonant with the upregulation of the mitochondrial Ca2+ uniporter complex and better preservation of SERCA1 and MICU1. These findings suggest that the mechanistic bases for repeated bout protection involve adaptation of Ca2+ regulation. [ABSTRACT FROM AUTHOR]

Millipedes increase the duty ratio and wavelength of their gait to enhance thrust force against resistive load. However, the underlying control mechanisms responsible for generating such adaptive gaits remain elusive. In this study, we proposed a decentralized control law based on the concept of 'discrepancy function'. Our proposed walking controller successfully reproduced the load-adaptive gaits of millipedes on the inclined ground. Furthermore, we evaluated the adaptability of our controller to horizontal resistive forces that hinder forward walking. Our simulation results suggest that the millipede-inspired controller could be beneficial for multi-legged robots equipped with leg actuators operating under limited motor outputs. [ABSTRACT FROM AUTHOR]

Background: The Columbia Muscle Cramp Scale (CMCS) is a useful tool for evaluating muscle cramps commonly observed in patients with amyotrophic lateral sclerosis (ALS). The CMCS comprises five subdomains: triggering factors, frequency, location, severity, and the degree to which cramps affect overall daily living. Aim: This study aimed to evaluate the reliability of the CMCS, which was translated into Japanese. Methods: Thirty patients with ALS (17 men and 13 women) from seven facilities were evaluated twice by two different evaluators (doctors, nurses, physical therapists, occupational therapists, and speech‐language‐hearing therapists). The degree of inter‐ and intra‐rater agreement was evaluated using kappa statistics. Weighted kappa statistics and 95% confidence intervals accounted for multiple‐order responses. Results: The average age was 60.4 (standard deviation: 10.4, range: 39–77) years. The kappa statistics for the inter‐rater reliability of the CMCS items showed moderate to very good agreement, ranging from 0.56 (cramp triggering) to 0.91 (daily activity) at visit 1 and 0.51 (severity) to 0.96 (daily activity) at visit 2. The kappa statistics for the intra‐rater reliability of the CMCS items also showed moderate to good agreement, ranging from 0.45 (frequency) to 0.79 (cramp triggering). Conclusion: The Japanese version of the CMCS demonstrated intra‐ and inter‐rater reliability agreement and is expected to be useful for evaluating muscle cramps in patients with ALS. [ABSTRACT FROM AUTHOR]

Power Doppler ultrasonography is used to measure blood flow within a given muscle, otherwise known as intramuscular blood flow. However, it is not fully understood how intramuscular blood flow and muscle oxygenation change with repetitive muscle contraction. The present study was conducted to assess changes in intramuscular blood flow and muscle oxygenation of the vastus lateralis (VL) during intermittent and incremental contractions. Fifteen healthy male subjects (21.7 ± 2.6 years) performed intermittent (5 s contraction, 5 s relaxation) and incremental isometric knee extensions at 30%, 40%, 50%, 60% and 70% of maximal voluntary contraction (MVC) until task failure. Intramuscular blood flow and muscle oxygen saturation (StO2${{S}_{{\mathrm{t}}{{{\mathrm{O}}}_2}}}$) were simultaneously measured using power Doppler ultrasonography and near‐infrared spectroscopy, respectively, from the right VL of the mid‐thigh. Intramuscular blood flow was increased from 0.5 ± 0.5% at rest to 13.9 ± 9.5% at task failure. Intramuscular blood flow significantly increased from rest to 30% and 40% MVC (P = 0.001), and StO2${{S}_{{\mathrm{t}}{{{\mathrm{O}}}_2}}}$ significantly decreased from 30% to 70% MVC (P = 0.004). These results indicate that intramuscular blood flow and StO2${{S}_{{\mathrm{t}}{{{\mathrm{O}}}_2}}}$ show different patterns of change, suggesting that the contribution of intramuscular blood flow to oxygen supply decreases within the VL at moderate and higher exercise intensities. What is the central question of this study?How do intramuscular blood flow and muscle oxygenation change with intermittent and incremental muscle contractions?What is the main finding and its importance?Intramuscular blood flow reached a plateau above moderate exercise intensities, but muscle oxygen saturation continued to decrease. These results indicate that the contribution of intramuscular blood flow to oxygen supply varies with exercise intensity. [ABSTRACT FROM AUTHOR]

A newly developed steerable-tip catheter (KC226; Zeon Medical, Tokyo, Japan) has been successfully used to cannulate a steeply angled pancreaticojejunostomy anastomotic stenosis following pancreaticoduodenectomy. This catheter, with a tip that can bend to a maximum angle of ±90°, overcomes challenges such as difficulty in accessing the anastomosis and selective pancreatic duct cannulation. The case study presented in the article demonstrates the effectiveness of this catheter in addressing the complexities of cannulation in steeply angled pancreaticojejunostomy anastomotic stenosis during balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP). [Extracted from the article]

The article discusses a case of successful endoscopic closure using hemoclips after a delayed perforation following colorectal endoscopic submucosal dissection (ESD). Delayed perforation is rare but can require emergency surgery in nearly half of cases. The use of hemoclips for closure was found to be effective, cost-efficient, and avoided potential complications associated with other closure methods like the over-the-scope (OTS) clip system. This case highlights the importance of context-dependent choices in endoscopic procedures to avoid emergency surgery and reduce costs. [Extracted from the article]

This study aimed to obtain angiotensin converting enzyme (ACE) inhibitory peptides from barley hordein, a protein rich in proline and glutamine, and to identify novel inhibitors. Hordein was hydrolyzed using four enzymes: pepsin, trypsin, papain, and orientase, an enzyme from Aspergillus oryzae known to cleave the C-terminal side of proline residues. The hydrolysate from orientase showed strong ACE inhibitory activity. LC-MS/MS analysis identified 35 peptides, including 23 derived from hordein and 9 known ACE inhibitors. After synthesizing 15 peptides, 7 showed significant ACE inhibition, all containing proline at the C-terminus. Notably, QQP, a new peptide, exhibited notable activity (IC50 40 μM). The results suggest that barley hordein is a valuable source of ACE inhibitory peptides, with QQP as a promising candidate. [ABSTRACT FROM AUTHOR]

Background: Apolipoprotein L1 gene ( APOL1 ) variants are risk factors for chronic kidney disease (CKD) among Black Americans. Data are sparse on the genetic epidemiology of CKD and the clinical association of APOL1 variants with CKD in West Africans, a major group in the Black population., Methods: We conducted a case-control study involving participants from Ghana and Nigeria who had CKD stages 2 through 5, biopsy-proven glomerular disease, or no kidney disease. We analyzed the association of CKD with APOL1 variants among participants with high-risk genotypes (two APOL1 risk alleles) and those with low-risk genotypes (fewer than two APOL1 risk alleles) by fitting logistic-regression models that controlled for covariates, including clinical site, age, and sex., Results: Among 8355 participants (4712 with CKD stages 2 through 5, 866 with glomerular diseases, and 2777 with no kidney disease), the prevalence of monoallelic APOL1 variants was 43.0% and that of biallelic APOL1 variants was 29.7%. Participants with two APOL1 risk alleles had higher odds of having CKD than those with one risk allele or no risk alleles (adjusted odds ratio, 1.25; 95% confidence interval [CI], 1.11 to 1.40), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.84; 95% CI, 1.30 to 2.61). Participants with one APOL1 risk allele had higher odds of having CKD than those with no risk alleles (adjusted odds ratio, 1.18; 95% CI, 1.04 to 1.33), as well as higher odds of focal segmental glomerulosclerosis (adjusted odds ratio, 1.61; 95% CI, 1.04 to 2.48). The inclusion of covariates did not modify the association of monoallelic and biallelic APOL1 variants with CKD or focal segmental glomerulosclerosis., Conclusions: In this study, monoallelic APOL1 variants were associated with 18% higher odds of CKD and 61% higher odds of focal segmental glomerulosclerosis; biallelic APOL1 variants were associated with 25% higher odds of CKD and 84% higher odds of focal segmental glomerulosclerosis. (Funded by the National Human Genome Research Institute and others.)., (Copyright © 2024 Massachusetts Medical Society.)