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We discuss the sharp interface limit, leading to a mean curvature flow energy, for the rate function of the large deviation principle of a Glauber+Kawasaki process with speed change. We provide an explicit formula of the limiting functional given by the mobility and the transport coefficient. [ABSTRACT FROM AUTHOR]

Background: Prehabilitation during neoadjuvant therapy has the potential to improve clinical outcomes. However, information on its global dissemination status is limited. This Japanese nationwide survey investigated the implementation status of and barriers to prehabilitation during neoadjuvant chemotherapy (NAC) for patients with locally advanced esophageal cancer in hospitals. Methods: This multicenter nationwide survey was conducted by post. The eligible facilities were 155 Japanese hospitals that had been certified within the last 10 years as authorized institutes for board-certified esophageal surgeons by the Japan Esophageal Society. We administered an original questionnaire to investigate the current status of prehabilitation during NAC. Results: The response rate was 75% (117/155 facilities). Forty-six facilities (39%) provided prehabilitation during NAC. The most frequently selected reasons for not providing or providing insufficient prehabilitation were lack of human resources, issues with the reimbursement of medical fees, difficulty in providing continuous prehabilitation during repeated inpatient and outpatient care, the lack of established standard prehabilitation programs, challenges in providing multidisciplinary prehabilitation, and difficulty in managing physical symptoms. Conclusion: We observed that the implementation rate of prehabilitation during NAC was low. Critical reasons were not only the lack of medical resources but also the lack of evidence-based standard prehabilitation programs during NAC and the lack of evidence for how to continuously deliver prehabilitation during NAC to patients with physical symptoms. [ABSTRACT FROM AUTHOR]

Purpose: The scapula is the second most popular donor site for mandibular reconstruction after the fibula. Scapula harvest is generally performed in the lateral decubitus position and the requirement of positional changes hamper the widespread use of the scapula. This study compared scapula harvest for immediate mandibular reconstruction between the supine and lateral decubitus positions. Methods: We reviewed the outcomes of 16 patients who underwent segmental mandibulectomy and immediate reconstruction of the scapula based on the angular branch of the thoracodorsal artery. The scapula was harvested in the lateral decubitus (lateral decubitus group) or supine position (supine group) in eight patients each. Several perioperative parameters were compared between the two groups. Results: One scapula was lost because of inadvertent injury of the angular branch in the supine group. The operative time was significantly shorter in the supine group than in the lateral decubitus group. Conclusion: Harvesting of the scapula in the supine position is a feasible option for immediate mandibular reconstruction. Although deep anatomic knowledge and technical expertise are necessary, this strategy can eliminate positional change and significantly reduce the operative time. [ABSTRACT FROM AUTHOR]

A selective and simple method was developed for the determination of four ethyleneamines (EAs), i.e., ethylenediamine (EDA), diethylenetriamine (DETA), triethylenetetramine (TETA), and tetraethylenepentamine (TEPA), by reversed-phase ion-pair chromatography with ultraviolet detection. The method is based on the on-line complexation of EAs with a Cu(II) ion added to the mobile phase. The Cu(II) complexes with EAs (Cu(II)-EA complexes) were well separated on a reversed-phased column, using 1-octanesulfonate as an ion-pairing reagent. The concentrations of 1-octanesulfonate and acetonitrile in the mobile phase significantly influenced the retention times of EAs. The high concentration of the Cu(II) ion in the mobile phase resulted in the increase of the baseline noise. A mixture of acetonitrile and 50 mM acetate buffer at pH 5.5 (23:77, v/v) which contains 0.5 mM CuSO4 and 20 mM 1-octanesulfonic acid sodium salt was used as the mobile phase. Cu(II)-EA complexes could be detected at 243 nm. The limits of quantification of EAs (S/N = 10) were 0.003 mM for EDA, DETA, and TETA and 0.01 mM for TEPA. The calibration curves were linear over three orders of magnitude of EA concentrations with high correlation coefficients (r2 = 1.000). The proposed method was successfully applied to determine EAs in epoxy resin curing agents. [ABSTRACT FROM AUTHOR]

This study examined the effects of pemafibrate, a selective peroxisome proliferator-activated receptor α agonist, on the serum biochemical parameters of male patients with coronary artery disease and metabolic syndrome (MetS). This was a post hoc analysis of a randomized, crossover study that treated hypertriglyceridemia with pemafibrate or bezafibrate for 24 weeks, followed by a crossover of another 24 weeks. Of the 60 patients enrolled in the study, 55 were male. Forty-one of 55 male patients were found to have MetS. In this sub-analysis, male patients with MetS (MetS group, n = 41) and those without MetS (non-MetS group, n = 14) were compared. The primary endpoint was a change in fasting serum triglyceride (TG) levels during pemafibrate therapy, and the secondary endpoints were changes in insulin resistance-related markers and liver function parameters. Serum TG levels significantly decreased (MetS group, from 266.6 to 148.0 mg/dL, p < 0.001; non-MetS group, from 203.9 to 97.6 mg/dL, p < 0.001); however, a percent change (%Change) was not significantly different between the groups (− 44.1% vs. − 51.6%, p = 0.084). Serum insulin levels and homeostasis model assessment of insulin resistance significantly decreased in the MetS group but not in the non-MetS group. %Change in liver enzyme levels was markedly decreased in the MetS group compared with that in the non-MetS group (alanine aminotransferase, − 25.1% vs. − 11.3%, p = 0.027; gamma-glutamyl transferase, − 45.8% vs. − 36.2%, p = 0.020). In conclusion, pemafibrate can effectively decrease TG levels in patients with MetS, and it may be a more efficient drug for improving insulin resistance and liver function in such patients. [ABSTRACT FROM AUTHOR]

This review aims to provide an overview of neoplastic lesions associated with genetic diseases affecting the female reproductive organs. It seeks to enhance our understanding of the radiological aspects in diagnosing genetic diseases including hereditary breast and ovarian cancer syndromes, Lynch syndrome, Peutz-Jeghers syndrome, nevoid basal cell carcinoma syndrome, and Swyer syndrome, and explores the patterns and mechanisms of inheritance that require elucidation. Additionally, we discuss the imaging characteristics of lesions occurring in other regions due to the same genetic diseases. [ABSTRACT FROM AUTHOR]

Invasive longhorn beetles are serious pests of tree stands worldwide. The rusty-spotted longhorn beetle, Apriona swainsoni (Hope) (Coleoptera: Cerambycidae: Lamiinae), is native to continental Asia, where it is a significant pest of legume trees. Its invasion into non-native ranges and damage to the local legume tree, Maackia amurensis, were first reported from Fukushima Prefecture, Japan, in 2021. This study investigated the biology of A. swainsoni in relation to adult emergence in Japan. Preliminary observations confirmed that A. swainsoni larvae create planned emergence holes on the host surface in late May. By exploiting these planned emergence holes, the adult emergence period was investigated in a field promenade of M. amurensis during the summer of 2022 and 2023. The researchers plugged the holes and recorded plug removal, resulting in the observation of 60 and 227 putative emergence events in respective years, with the majority occurring in early to mid-July. Further, during the summer of 2022, a periodic field survey of adult emergence was conducted, obtaining eight adults. Furthermore, a supplementary survey using infested logs maintained in a field cage demonstrated that the emergence period does not differ between sexes and the male-to-female ratio is one:one. Our results suggest that control efforts to suppress A. swainsoni adults in the field, such as insecticide spraying, should be prioritized in the relatively short, peak emergence period. This work indicates that the plug survey is useful for detecting the emergence period. [ABSTRACT FROM AUTHOR]

Trunk injection is a relatively new, environmentally friendly method to apply insecticides to trees which does not cause insecticide drift and environmental runoff. However, little is known about the effect of insecticide trunk injection on non-target arboreal ants (Hymenoptera: Formicidae) which can act as biological control agents of target tree pests. This study evaluated the effect of trunk injections on arboreal ants found on cherry trees treated with neonicotinoids (dinotefuran and thiamethoxam) for controlling the invasive longhorn beetle Aromia bungii (Faldermann) (Coleoptera: Cerambycidae). Arboreal ants represented by Crematogaster matsumurai Forel can prey on A. bungii eggs. Results of visual sampling 1 and 3 months after injections showed that injections did not reduce the number of ant species occurring on tree trunks. Additionally, injections did not eliminate 3 of 4 most abundant species on tree trunks or extrafloral nectaries including C. matsumurai. However, a decline of Lasius japonicus Santschi was observed on injected trees. Our preliminary short-term survey suggests the possibility that chemical control by trunk injection and biological control by arboreal ants are compatible in A. bungii management. However, further research is needed to clarify the mechanism of L. japonicus decline and long-term consequences of trunk injection on arboreal ant composition. [ABSTRACT FROM AUTHOR]

Domains are functional and structural units of proteins that govern various biological functions performed by the proteins. Therefore, the characterization of domains in a protein can serve as a proper functional representation of proteins. Here, we employ a self-supervised protocol to derive functionally consistent representations for domains by learning domain-Gene Ontology (GO) co-occurrences and associations. The domain embeddings we constructed turned out to be effective in performing actual function prediction tasks. Extensive evaluations showed that protein representations using the domain embeddings are superior to those of large-scale protein language models in GO prediction tasks. Moreover, the new function prediction method built on the domain embeddings, named Domain-PFP, substantially outperformed the state-of-the-art function predictors. Additionally, Domain-PFP demonstrated competitive performance in the CAFA3 evaluation, achieving overall the best performance among the top teams that participated in the assessment. A self-supervised learning method to generate functionally informed embedding representations for protein domains, capable of performing protein function prediction with state-of-the-art accuracy. [ABSTRACT FROM AUTHOR]

Patient-derived xenograft (PDX) mouse models are useful for deepening our understanding of the biology of malignant lymphoma; however, factors associated with the success of the PDX lymphoma model are largely unknown. We retrospectively analyzed the characteristics of 66 xenotransplantations from 65 patients. In all, 43 (65%) specimens were obtained from patients aged > 60 years, and 42 (64%) specimens were obtained at diagnosis. Specimens were obtained from patients with the following diseases: diffuse large B-cell lymphoma (n = 30), intravascular large B-cell lymphoma (n = 12), follicular lymphoma (n = 8), peripheral T-cell lymphoma (n = 7), mantle cell lymphoma (n = 2), and other (n = 7). The specimens were sourced mainly from bone marrow (n = 31, 47%) and extranodal tumors (n = 13, 20%). Engraftment was successful in 33/66 (50%) xenotransplantations. The median age of patients who provided successful specimens was significantly higher than that for unsuccessful specimens (p = 0.013). Specimens with a high proportion of tumor cells in the graft and those obtained from patients with relapsed/refractory disease showed higher tendencies toward successful engraftment. Taken together, these data suggest that tumor cells with a highly malignant potential might have a high likelihood of engraftment. [ABSTRACT FROM AUTHOR]

This study evaluated the effects of the effortful swallow (ES) on pharyngeal cavity volume using three-dimensional kinematic analyses. Nine healthy volunteers (30.7 ± 7.8 years old) underwent a CT scan while swallowing 10 ml of honey thick liquid using no maneuvers (control) and during an ES. Upper and lower volumes (bordered by valleculae) of the pharyngeal air column and the bolus were measured at every frame and were compared between ES and control swallows. Duration of pharyngeal obliteration and the timing of swallowing events were also measured. Maximum volume and volume at the onset of hyoid anterosuperior movement using ES were significantly smaller than those in control swallows (p = 0.012, p = 0.015) in the upper pharynx but not significantly different in lower pharynx. Minimum pharyngeal volume was sustained for a longer time when ES was used compared to control swallows in both upper and lower pharynx (upper p = 0.016, lower p = 0.027). Onset of velopharyngeal closure was earlier when comparing ES and control swallows (p = 0.04). Termination of all events was significantly delayed when the ES was used (p < 0.05). Changes in the upper pharyngeal volume and in the onset of velopharyngeal closure suggest earlier pharyngeal constriction when using the ES. Longer pharyngeal obliteration and prolonged termination of velopharyngeal closure and epiglottis inversion suggest the prolonged pharyngeal constriction during the ES. These findings suggest the ES can be useful for improving the efficiency of swallowing. [ABSTRACT FROM AUTHOR]

Malaria control initiatives require rapid and reliable methods for the detection and monitoring of molecular markers associated with antimalarial drug resistance in Plasmodium falciparum parasites. Ngodhe island, Kenya, presents a unique malaria profile, with lower P. falciparum incidence rates than the surrounding region, and a high proportion of sub-microscopic and low-density infections. Here, using custom dual-indexing and Illumina next generation sequencing, we generate resistance profiles on seventy asymptomatic and low-density P. falciparum infections from a mass drug administration program implemented on Ngodhe island between 2015 and 2016. Our assay encompasses established molecular markers on the Pfcrt, Pfmdr1, Pfdhps, Pfdhfr, and Pfk13 genes. Resistance markers for sulfadoxine-pyrimethamine were identified at high frequencies, including a quintuple mutant haplotype (Pfdhfr/Pfdhps: N51I, C59R, S108N/A437G, K540E) identified in 62.2% of isolates. The Pfdhps K540E biomarker, used to inform decision making for intermittent preventative treatment in pregnancy, was identified in 79.2% of isolates. Several variants on Pfmdr1, associated with reduced susceptibility to quinolones and lumefantrine, were also identified (Y184F 47.1%; D1246Y 16.0%; N86 98%). Overall, we have presented a low-cost and extendable approach that can provide timely genetic profiles to inform clinical and surveillance activities, especially in settings with abundant low-density infections, seeking malaria elimination. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to evaluate our surgical strategy for acute aortic dissection Stanford A and determine whether it is safe regardless of the experience of the primary surgeon. Methods: Between April 2015 and September 2020, a total of 160 patients who underwent open surgery for type A aortic dissection at Shonan Kamakura General Hospital were reviewed. Data were collected from reviews of computerized medical records. From this study cohort, we retrospectively reviewed the cases of trainee (group T) and experienced primary surgeons (group E). We evaluated rates of 30 day and in-hospital mortality, stroke, aortic reintervention, and mid-term survival for both groups. Results: The rates of 30 day and in-hospital mortalities in group T were 5.1 and 7.7%, respectively, whereas those in group E were 4.7 and 4.7%, respectively. One and 3 year survival rates in group T were 88.4 and 87.1% and in group E were 95.3 and 95.3%, respectively (log-rank test, p = 0.11). The 1 year and 3 year rates of freedom from reintervention were 90.9 and 72.8% in group T and 96.8 and 92.7% in group E, respectively (log-rank test, p = 0.29). The permanent neurological dysfunction rate was 8.1% overall, 8.5% in group T, and 7.0% in group E, with no significant difference. Conclusions: Our surgical strategy for acute type A aortic dissection is safe and appropriate regardless of the experience of the primary surgeon. [ABSTRACT FROM AUTHOR]

This paper is concerned with a general class of fully nonlinear parabolic equations with monotone nonlocal terms. We investigate the quasiconvexity preserving property of positive, spatially coercive viscosity solutions. We prove that if the initial value is quasiconvex, the viscosity solution to the Cauchy problem stays quasiconvex in space for all time. Our proof can be regarded as a limit version of that for power convexity preservation as the exponent tends to infinity. We also present several concrete examples to show applications of our result. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the impact of plasma trough concentrations of abiraterone (ABI) and its metabolite Δ4-abiraterone (D4A) and related polymorphisms on adverse events (AEs) in patients with metastatic prostate cancer who received abiraterone acetate (AA). Methods: This prospective study enrolled patients with advanced prostate cancer treated with AA between 2016 and 2021. Plasma trough concentrations of ABI and D4A were measured using high-performance liquid chromatography. The impact of HSD3B1 rs1047303, SRD5A2 rs523349, and cytochrome P450 family 3A member 4 rs2242480 polymorphisms on plasma concentrations of ABI and D4A and the incidence of AEs were also assessed. Results: In 68 patients treated with AA, the median ABI and D4A concentrations were 18.1 and 0.94 ng/mL, respectively. The high plasma trough concentration of ABI (≥ 20.6 ng/mL) was significantly associated with the presence of any AE and its independent risk factor based on multivariable analysis (odds ratio, 7.20; 95% confidence interval (CI): 2.20–23.49). Additionally, a high plasma trough concentration of ABI was an independent risk factor of time to withdraw AA (hazard ratio, 4.89; 95% CI: 1.66–14.38). The risk alleles of three polymorphisms were not statistically associated with the ABI and D4A concentrations and the incidence of AEs. Conclusions: The plasma trough concentration of ABI is associated with the presence of AEs and treatment failure after AA administration. ABI concentration monitoring may be useful in patients with prostate cancer who received AA. [ABSTRACT FROM AUTHOR]

Aberrant muscle bundles of approximately 10 cm in length, running subcutaneously from the posterior surface of sacrum to the iliac crest, were found on both sides of three males among 93 cadavers of anatomical courses for medical students. Since no precedent of this anomaly has been described in the literature, we present its morphology and discuss the significance of this muscle. This muscle originated from the tendinous fibers of the superficial-most layer of the sacral part of thoracolumbar fascia, became muscularized near the posterior superior iliac spine, passed over the origins of the gluteus maximus and medius, and inserted on the iliac crest. Some bundles crossed the iliac crest to insert between sublayers of the posterior layer of the thoracolumbar fascia. The superior cluneal nerves passed above, below, or penetrated the muscle. Branches from the segmentally lowest one or the conjoined lowest two entered the aberrant muscles. Considering its location and multi-layered structure, the muscle is likely to be a muscularized bundle of the thoracolumbar fascia. The aberrant muscle is also similar to the serratus posterior inferior in its location at the lateral end of the thoracolumbar fascia and below the latissimus dorsi. Nevertheless its innervation from the posterior rami of the spinal nerves and partial fusion at its origin implies a close relationship to the iliocostalis. This aberrant muscle may also be of clinical interest since it is potentially involved in the entrapment of the superior cluneal nerves as it runs along the caudolateral edge of the thoracolumbar fascia. [ABSTRACT FROM AUTHOR]

The previous studies reported that different volumes of thick liquid had an impact on spatiotemporal characteristics and pharyngeal response of swallowing. However, the bolus flow and swallowing motion pattern were different between thick and thin liquids. The effects of thin bolus volume on pharyngeal swallowing, especially true vocal cord (TVC) closure is still unclear. This study assessed the temporal characteristics when swallowing different volumes of thin liquid to determine the mechanical adaptation using 320-row area detector computed tomography (320-ADCT) and investigated a change of swallowing physiology including laryngeal closure, particularly TVC closure. Fourteen healthy women (28-45 years) underwent 320-ADCT while swallowing of 3, 10, and 20 ml of thin liquid barium in 45° semi-reclining position. Kinematic analysis was performed for each swallow including temporal characteristic, structural movements while swallowing, and maximal cross-sectional area of the upper esophageal sphincter (UES) opening. Bolus head reached to pharynx and esophagus earlier in larger volume significantly, indicating faster bolus transport as volume increased. There were significant effects on swallowing mechanism revealing earlier TVC closure and UES opening with increasing volume. Maximum cross-sectional area of the UES opening was increased to accommodate a larger bolus. Differences in mechanical adaptation through bolus transit and motion of swallowing structures were detected across increasing volumes. These volume-dependent adaptations potentially reduce the risk of aspiration. Understanding the swallowing physiological changes as volume increased is helpful for diagnosis and treatment of dysphagia patients as well as outcomes of swallowing rehabilitation in clinical practice. [ABSTRACT FROM AUTHOR]

Wearable sensors have seen remarkable recent technological developments, and their role in healthcare is expected to expand. Specifically, monitoring tissue circulation in patients who have undergone reconstructive surgery is critical because blood flow deficiencies must be rescued within hours or the transplant will fail due to thrombosis/haematoma within the artery or vein. We design a wearable, wireless, continuous, multipoint sensor to monitor tissue circulation. The system measures pulse waves, skin colour, and tissue temperature to reproduce physician assessment. Data are analysed in real time for patient risk using an algorithm. This multicentre clinical trial involved 73 patients who underwent transplant surgery and had their tissue circulation monitored until postoperative day 7. Herein, we show that the overall agreement rate between physician and sensor findings is 99.2%. In addition, the patient questionnaire results indicate that the device is easy to wear. The sensor demonstrates non-invasive, real-time, continuous, multi-point, wireless, and reliable monitoring for postoperative care. This wearable system can improve the success rate of reconstructive surgeries. [ABSTRACT FROM AUTHOR]

Background: Common bile duct stones (CBDSs) occasionally cause serious diseases, and endoscopic extraction is the standard procedure for CBDS. To prevent biliary complications, cholecystectomy is recommended for patients who present with gallbladder (GB) stones after endoscopic CBDS extraction. However, CBDS can occasionally recur. To date, the occurrence of CBDS after endoscopic CBDS extraction and subsequent cholecystectomy is not fully understood. Hence, the current study aimed to evaluate the incidence of postoperative CBDSs. Methods: This retrospective observational study included consecutive patients who underwent postoperative endoscopic retrograde cholangiography after endoscopic CBDS extraction and subsequent cholecystectomy between April 2012 and June 2021 at our institution. After endoscopic CBDS extraction, a biliary plastic stent was inserted to prevent obstructive cholangitis. Endoscopic retrograde cholangiography was performed to evaluate postoperative CBDSs after cholecystectomy until hospital discharge. The outcomes were the incidence of postoperative CBDSs and CBDSs/sludge. Moreover, the predictive factors for postoperative CBDSs were evaluated via univariate and multivariate analyses. Results: Of eligible 204 patients, 52 patients (25.5%) presented with postoperative CBDSs. The incidence rate of CBDS/sludge was 36.8% (n = 75). Based on the univariate analysis, the significant predictive factors for postoperative CBDSs were ≥ 6 CBDSs, presence of cystic duct stones, and ≥ 10 GB stones (P < 0.05). Moreover, male sex and < 60-mm minor axis in GB might be predictive factors (P < 0.10). Based on the multivariate analysis, ≥ 6 CBDSs (odds ratio = 6.65, P < 0.01), presence of cystic duct stones (odds ratio = 4.39, P < 0.01), and ≥ 10 GB stones (odds ratio = 2.55, P = 0.01) were independent predictive factors for postoperative CBDSs. Conclusions: The incidence of postoperative CBDS was relatively high. Hence, patients with predictive factors for postoperative CBDS must undergo imaging tests or additional endoscopic procedure after cholecystectomy. [ABSTRACT FROM AUTHOR]

Postoperative pain is the main reason for delayed recovery after herniorrhaphy. Preoperative glucocorticoid administration may improve postoperative recovery. The present study assessed the efficacy of preoperative glucocorticoids in facilitating recovery after herniorrhaphy. Randomized controlled trials (RCTs) conducted up to January 2021 were searched in electronic databases and trial registries. Meta-analyses were performed using random effects models. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of evidence. Seven RCTs (744 patients) were included in the meta-analysis. Preoperative glucocorticoid administration reduced patients' pain on postoperative day 0 (standard mean difference [SMD] = − 0.73, 95% confidence interval [CI] − 1.45 to − 0.01; I2 = 94%). However, there was no marked difference in rescue analgesic use (risk ratio [RR] = − 0.06, 95% CI − 0.28 to − 0.16; I2 = 0%) or vomiting (RR = 0.78, 95% CI 0.50–1.20; I2 = 30%) between preoperative glucocorticoid administration and control. The certainty of evidence was moderate because of inconsistencies or imprecision. No serious adverse effects were observed. Preoperative glucocorticoid administration reduced pain in patients following herniorrhaphy without increasing the occurrence of adverse events. Further studies will be required to confirm the efficacy of preoperative glucocorticoids. [ABSTRACT FROM AUTHOR]

A highly invasive alien species in North America and Europe, the Asian longhorned beetle Anoplophora glabripennis (Motschulsky) (Coleoptera: Cerambycidae), has been detected in various parts of Japan since 2020. In addition to damaging host trees, A. glabripennis may severely impact the Japanese ecosystem by interfering with A. chinensis (Foster) (formerly called A. malasiaca), a common and related native species with a similar niche. To assess the potential risk of reproductive interference between the two species, mating behavior between interspecific females and males was examined in the laboratory using field-collected sample individuals. Males of both species mounted on female A. glabripennis and attempted to insert genitalia at similar frequencies (approximately 50%), but A. chinensis males always failed to copulate. In contrast, male A. glabripennis did not have sexual behavior with female A. chinensis. The results show that mating between the two species is typically unsuccessful, although recent research showed that the two species could produce a hybrid when paired for 4 weeks. The erroneous interspecific mating attempts may reduce both species' fitness. Therefore, the population-level impact of this reproductive interference should be assessed. [ABSTRACT FROM AUTHOR]

A 72-year-old man was treated by two-regimen chemotherapies for unresectable advanced gastric cancer with metastatic lymph nodes near the pancreatic head, followed by the third-line chemotherapy using nivolumab (Nivo). Ten days after the two-course Nivo chemotherapy, grade 4 thrombocytopenia (TCP) occurred according to the Common Terminology Criteria for Adverse Events. He was treated by steroid and Helicobacter pylori (HP) eradication therapies. Consequently, the platelet count improved rapidly without any complications. Before resuming the Nivo therapy, the platelet count was already improved. Fourth-line chemotherapy was then started using irinotecan. After three courses, his general condition worsened. Unfortunately, the patient died 18 months after gastric cancer diagnosis. Although rare, severe TCP is potentially a fatal complication of chemotherapy using immune checkpoint inhibitors. In addition to standard treatment with steroids, HP eradication therapy may be effective for Nivo-associated TCP. [ABSTRACT FROM AUTHOR]

Last year saw a breakthrough in protein structure prediction, where the AlphaFold2 method showed a substantial improvement in the modeling accuracy. Following the software release of AlphaFold2, predicted structures by AlphaFold2 for proteins in 21 species were made publicly available via the AlphaFold Database. Here, to facilitate structural analysis and application of AlphaFold2 models, we provide the infrastructure, 3D-AF-Surfer, which allows real-time structure-based search for the AlphaFold2 models. In 3D-AF-Surfer, structures are represented with 3D Zernike descriptors (3DZD), which is a rotationally invariant, mathematical representation of 3D shapes. We developed a neural network that takes 3DZDs of proteins as input and retrieves proteins of the same fold more accurately than direct comparison of 3DZDs. Using 3D-AF-Surfer, we report structure classifications of AlphaFold2 models and discuss the correlation between confidence levels of AlphaFold2 models and intrinsic disordered regions. 3D-AF-Surfer is presented as a computational resource for real-time protein structure comparison search between AlphaFold2 models and PDB entries within seconds to a few minutes. [ABSTRACT FROM AUTHOR]

Background: Vonoprazan is a potassium competitive acid blocker used to treat erosive gastroesophageal reflux disease (GERD) with stronger, more stable acid-suppressing effects than proton pump inhibitors (PPIs). This study clarified the usefulness and superiority of vonoprazan administered every second day over PPIs in the maintenance therapy of erosive GERD. Methods: This is a prospective, multicenter, open-label, two-period randomized cross-over study. Patients were randomized to either the vonoprazan-lansoprazole (VP-LZ) group, who were given vonoprazan 10 mg for the first 4 weeks and then lansoprazole 15 mg for the next 4 weeks both administered once every second day, or the lansoprazole-vonoprazan (LZ-VP) group, who were treated in reverse. GERD symptoms were compared using symptom diaries, the frequency scale for symptoms of GERD (FSSG), and the gastrointestinal symptom rating scale (GSRS). Results: We enrolled 122 patients between December 2017 and May 2019. Symptoms were well controlled in vonoprazan administration and lansoprazole administration were 93.6% and 82.1%, respectively, with a significant difference on McNemar's test (P = 0.003). During the second 4 weeks, 94.4% and 76.7% of patients in the VP-LZ and LZ-VP groups, respectively, were well controlled following for ≥ 6 consecutive days a week (P = 0.009). During the first 4 weeks, 96.7% and 80.0% of patients were well controlled with < 1 weekly in the VP-LZ and LZ-VP groups, respectively, during the first 4 weeks (P = 0.007). GERD symptoms, assessed via FSSG and GSRS, significantly decreased with vonoprazan administration once every second day. Conclusions: Vonoprazan administered once every second day could be an effective alternative to PPIs in the maintenance treatment of erosive GERD (UMIN000030393). [ABSTRACT FROM AUTHOR]

This paper describes the findings of a numerical and experimental study on the heat transfer coefficient and pressure drop in micro-lattice blocks fabricated by selective laser metal melting and subjected to forced air convection. In particular, the influence of the unit-cell topology on the thermofluid performance of the lattice structure is examined in detail. In the present numerical study, five lattice block designs (BCC, BCCZ, FCC, FCCZ and F2BCC) are considered for investigation. Regarding effective thermal conductivity, the FCC and FCCZ lattices offer the best performance among the various lattices. In terms of heat transfer capacity per unit mass, the BCC and BCCZ lattices exhibit superior characteristics relative to the other lattices. Also, F2BCC lattice offers the lowest pressure loss for a given relative density. In addition, it is found that the heat transfer coefficients obtained by experiment lie between two numerical results having different strut diameter, which is due to the fact that the equivalent strut diameter in the as-manufactured samples is greater, due to the present of additional metal particles fused onto the surfaces of some struts. Moreover, it is found from our experimental investigation that the heat transfer coefficient h for the BCCZ is approximately 1.3 times higher than that for the BCC lattice for the same pressure loss. [ABSTRACT FROM AUTHOR]

Background: The mortality and risk factors of severe disease and death due to arterial and venous thromboembolism (ATE and VTE, respectively) in patients with inflammatory bowel disease (IBD) remain unclear, especially in Asia. Aims: This study aimed to reveal the mortality and risk factors of TE in IBD patients in Japan. Methods: In the primary surveillance, responses to questionnaires regarding the number of cases of severe TE and TE-associated death in IBD patients in a span of over the past 10 years were obtained from 32 institutions in Japan. In the secondary surveillance, detailed data about IBD patients with TE were collected. The characteristics, laboratory data, therapy status, and situation at the time of TE development were retrospectively collected, and the data were compared between the patients with and without severe TE and TE-associated death. Results: The incidence of TE was 1.89% among 31,940 IBD patients. The frequencies of severe TE and TE-associated mortality were 10.7% and 1.0% among the total IBD and TE with IBD patients, respectively. The only risk factor for severe ATE and ATE-associated death was ischemic heart disease. The independent risk factors for severe VTE and VTE-associated death were age (≤ 45 years old), the site of VTE, and disease severity, with anti-TNF therapy as a potential negative risk factor. Patients with severe VTE had a high risk of developing persistent VTE and sequelae. Conclusion: Unlike ATE, the incidence of VTE was comparable in Asian and Western countries. Therapeutic and prophylactic strategies for managing IBD-associated TE in Asia are urgently needed. [ABSTRACT FROM AUTHOR]

Characterising the genomic variation and population dynamics of Plasmodium falciparum parasites in high transmission regions of Sub-Saharan Africa is crucial to the long-term efficacy of regional malaria elimination campaigns and eradication. Whole-genome sequencing (WGS) technologies can contribute towards understanding the epidemiology and structural variation landscape of P. falciparum populations, including those within the Lake Victoria basin, a region of intense transmission. Here we provide a baseline assessment of the genomic diversity of P. falciparum isolates in the Lake region of Kenya, which has sparse genetic data. Lake region isolates are placed within the context of African-wide populations using Illumina WGS data and population genomic analyses. Our analysis revealed that P. falciparum isolates from Lake Victoria form a cluster within the East African parasite population. These isolates also appear to have distinct ancestral origins, containing genome-wide signatures from both Central and East African lineages. Known drug resistance biomarkers were observed at similar frequencies to those of East African parasite populations, including the S160N/T mutation in the pfap2mu gene, which has been associated with delayed clearance by artemisinin-based combination therapy. Overall, our work provides a first assessment of P. falciparum genetic diversity within the Lake Victoria basin, a region targeting malaria elimination. [ABSTRACT FROM AUTHOR]

Engineering polyketide synthases is one of the most promising ways of producing a variety of polyketide derivatives. Exploring the undiscovered chemical space of this medicinally important class of middle molecular weight natural products will aid in the development of improved drugs in the future. In previous work, we established methodology designated 'module editing' to precisely manipulate polyketide synthase genes cloned in a bacterial artificial chromosome. Here, in the course of investigating the engineering capacity of the rapamycin PKS, novel rapamycin derivatives 1–4, which lack the hemiacetal moiety, were produced through the heterologous expression of engineered variants of the rapamycin PKS. Three kinds of module deletions in the polyketide synthase RapC were designed, and the genetically engineered vectors were prepared by the in vitro module editing technique. Streptomyces avermitilis SUKA34 transformed with these edited PKSs produced new rapamycin derivatives. The planar structures of 1–4 established based on 1D and 2D NMR, ESI–TOF–MS and UV spectra revealed that 2 and 3 had skeletons well-matched to the designs, but 1 and 4 did not. The observations provide important insights into the mechanisms of the later steps of rapamycin skeletal formation as well as the ketone-forming oxygenase RapJ. [ABSTRACT FROM AUTHOR]

Protein 3D structure prediction has advanced significantly in recent years due to improving contact prediction accuracy. This improvement has been largely due to deep learning approaches that predict inter-residue contacts and, more recently, distances using multiple sequence alignments (MSAs). In this work we present AttentiveDist, a novel approach that uses different MSAs generated with different E-values in a single model to increase the co-evolutionary information provided to the model. To determine the importance of each MSA's feature at the inter-residue level, we added an attention layer to the deep neural network. We show that combining four MSAs of different E-value cutoffs improved the model prediction performance as compared to single E-value MSA features. A further improvement was observed when an attention layer was used and even more when additional prediction tasks of bond angle predictions were added. The improvement of distance predictions were successfully transferred to achieve better protein tertiary structure modeling. [ABSTRACT FROM AUTHOR]

Background: A catheter fragment with inaccessible ends can be retrieved using the well-known two-step method: making a free end with a pigtail catheter and seizing it with a snare catheter. Here we propose an easier and faster modification, named the "pigtail through snare" technique. Case presentation: A 61-year-old female patient underwent removal of a central venous catheter fragment migrating to the right atrium. Both ends located in the right atrial appendage and left hepatic vein were inaccessible. Initially, a snare loop was opened in the inferior vena cava and a pigtail catheter was advanced through the snare loop to hook the catheter fragment. The free end was created by pulling the pigtail catheter, dragged automatically into the snare loop, grasped, and retrieved immediately. Conclusions: By passing the pigtail catheter through the snare loop in advance, the snaring maneuver becomes easy and fast in retrieving the catheter fragment with inaccessible ends. [ABSTRACT FROM AUTHOR]

Background: Adherence to medications is important to maintain disease under control and to prevent complications in pregnant patients with ulcerative colitis (UC). To evaluate the incidence of non-adherence during pregnancy and its effect on relapse and pregnancy outcomes, we conducted a multicenter prospective study using a patient self-reporting system without physician interference. Methods: Sixty-eight pregnant UC women were recruited from 17 institutions between 2013 and 2019. During the course of pregnancy, questionnaires were collected separately from patients and physicians, to investigate the true adherence to medications, disease activity, and birth outcomes. Multivariable logistic regression analysis was performed to identify the risk factors for the relapse or adverse pregnancy outcomes. Results: Of 68 pregnancy, 15 adverse pregnancy outcomes occurred in 13 patients. The rate of self-reported non-adherence was the greatest to mesalamines in the first trimester, which was significantly higher than physicians' estimate (p = 0.0116), and discontinuation was observed in 42.1% of non-adherent group. Logistic regression analysis revealed non-adherence as an independent risk factor for relapse [odds ratio (OR) 7.659, 95% CI 1.928–30.427, p = 0.038], and possibly for adverse pregnancy outcome (OR 8.378, 95% CI 1.350–51.994, p = 0.023). Among the subgroup of patients treated with oral mesalamine alone, the non-adherence was confirmed to be an independent risk factor for relapse (p = 0.002). Conclusion: Non-adherence to mesalamine was underestimated by physicians in pregnant UC patients and contributed to disease relapse and possibly on pregnancy outcomes. Preconceptional education regarding safety of medications and risk of self-discontinuation is warranted. [ABSTRACT FROM AUTHOR]

Pouchitis is a frequent complication of surgical treatment of ulcerative colitis (UC), and is typically treated using antimicrobials. If pouchitis is refractory to antimicrobials, screening for complications, such as cytomegalovirus (CMV) infection, is necessary. However, the optimal approach to management of pouchitis complicated by CMV infection is unclear. We report the case of a 41-year-old female patient with UC presenting with pouchitis associated with CMV infection; she had received subtotal colectomy/ileal pouch anal anastomosis (IPAA). She was admitted to hospital with persistent fever, epigastric discomfort, and watery diarrhea despite receiving antibiotics. Laboratory findings showed inflammation and reactivation of CMV infection accompanied by liver injury. The endoscopic findings showed inflammation of the pouch and ileal mucosa on the oral side with extensive and deep punched-out ulcers. Immunohistological staining of biopsy specimens from an ulcerated lesion demonstrated CMV infection. Therefore, we diagnosed the patient with pouchitis complicated by CMV infection. The patient was treated with ganciclovir and infliximab, which resolved her symptoms and led to the disappearance of CMV-positive cells. There has been no recurrence of pouchitis. CMV infection should be considered in patients with UC who develop refractory pouchitis. [ABSTRACT FROM AUTHOR]

Pancreatic lymphoepithelial cysts (LECs) are rare cystic lesions filled with a keratinous substance and lined by squamous epithelium with underlying lymphoid tissue. Because pancreatic LECs are entirely benign, correct preoperative diagnosis is important to avoid unnecessary surgery. However, the imaging features of pancreatic LECs are not specific and preoperative diagnosis has proven difficult. A pancreatic mass was incidentally detected through abdominal ultrasonography in a 63-year-old male presenting without any symptoms. Computed tomography showed an exophytic cystic lesion in the pancreatic head. The lesion had heterogeneous high signal intensity with partial low intensity on T2-weighted magnetic resonance imaging (MRI) and high signal intensity on diffusion MRI. Endoscopic ultrasound (EUS) examination showed an encapsulated cystic lesion with relatively homogenous and highly echoic contents. EUS-guided fine-needle aspiration (EUS-FNA) revealed caseous appearance and rare fragments of apparently benign squamous epithelium on a background of keratinous debris, cyst contents, and scattered lymphocytes. We diagnosed a pancreatic LEC and opted for conservative management without surgery. Pathological evaluation based on images obtained through EUS-FNA showed macro- and microscopic features that were critical to determining the management strategy. In conclusion, the imaging and pathological features of pancreatic LECs can inform preoperative diagnosis, which may enable conservative management. [ABSTRACT FROM AUTHOR]

Hepatic biliary injury is one of the most common complications in cholecystectomy and is frequently accompanied by arterial injuries. Because there are several anatomical variations of the hepatic ducts, including the accessory hepatic ducts (AHDs), it is important to consider not only the anatomical position of the hepatic ducts but also those of the AHDs in cholecystectomy. However, the topographical relationships between the AHDs and the hepatic arteries are still poorly understood. In the present study we show that AHDs were observed in 7 out of 59 (11.9%) of the cadavers. There was a single AHD in the 6 out of the 7 cadavers and double AHDs in one. In these cases, the right AHDs emerged from the anterior medial segment of the liver piercing the parenchyma, while the left AHDs emerged directly from the anterior part of the caudate lobe. The right AHDs ran anterior to the right hepatic artery, while the left AHDs ran posterior to the hepatic arteries. The topographical relationship between the AHD and the hepatic artery system was thus reversed in the cases of the right and the left AHDs. [ABSTRACT FROM AUTHOR]

In this study, we present an analysis of metagenome sequences obtained from a filtrate of a siphon tissue homogenate of otter clams (Lutraria rhynchaena) with swollen-siphon disease. The viral signal was mined from the metagenomic data, and a novel circular ssDNA virus was identified. Genomic features and phylogenetic analysis showed that the virus belongs to the phylum Cressdnaviricota, which consists of viruses with circular, single-stranded DNA (ssDNA) genomes. Members of this phylum have been identified in various species and in environmental samples. The newly found virus is distantly related to the currently known members of the phylum Cressdnaviricota. [ABSTRACT FROM AUTHOR]

One major bottleneck in natural product drug development is derivatization, which is pivotal for fine tuning lead compounds. A promising solution is modifying the biosynthetic machineries of middle molecules such as macrolides. Although intense studies have established various methodologies for protein engineering of type I modular polyketide synthase(s) (PKSs), the accurate targeting of desired regions in the PKS gene is still challenging due to the high sequence similarity between its modules. Here, we report an innovative technique that adapts in vitro Cas9 reaction and Gibson assembly to edit a target region of the type I modular PKS gene. Proof-of-concept experiments using rapamycin PKS as a template show that heterologous expression of edited biosynthetic gene clusters produced almost all the desired derivatives. Our results are consistent with the promiscuity of modular PKS and thus, our technique will provide a platform to generate rationally designed natural product derivatives for future drug development. Several different genetic strategies have been reported for the modification of polyketide synthases but the highly repetitive modular structure makes this difficult. Here the authors report on an adapted Cas9 reaction and Gibson assembly to edit a target region of the polyketide synthases gene in vitro. [ABSTRACT FROM AUTHOR]

Success of an invasive organism depends on the level of biotic resistance from native species. Understanding the mechanism of biotic resistance is critical to the management of invasive species, but such case studies are sparse. Native to parts of Asia and Russia, the red-necked longhorn beetle Aromia bungii (Faldermann) (Coleoptera: Cerambycidae) recently invaded Germany, Italy, and Japan, causing serious damage to Rosaceae trees. To identify any specific mechanism of biotic resistance to A. bungii, we investigated whether Japanese native ants play a role in the biotic resistance through predation, because ants can impact many arthropods as generalist predators. In laboratory experiments, A. bungii eggs or hatchlings were offered to four ant species. Three species exhibited predatory behaviors toward the eggs within 30 min, and obvious damage was confirmed on the eggs within 2 days. Two ant species fatally damaged hatchlings within 30 min. In field surveys, we found a negative correlation between the number of A. bungii frass-ejection holes and the number of collected ants on tree trunks. These results suggested that Japanese native ant fauna can play a certain role in biotic resistance to A. bungii. [ABSTRACT FROM AUTHOR]

To study the size-resolved characteristics of airborne bacterial community composition, diversity, and abundance, outdoor aerosol samples were analysed by 16S rRNA gene-targeted quantitative PCR and amplicon sequencing with Illumina MiSeq. The samples were collected using size-resolved samplers between August and October 2016, at a suburban site in Toyama City and an urban site in Yokohama City, Japan. The bacterial communities were found to be dominated by Actinobacteria, Firmicutes, and Proteobacteria. At the genus level, we found a high abundance of human skin-associated bacteria, such as Propionibacterium, Staphylococcus, and Corynebacterium, in the urban site. Whereas, a high abundance of bacteria associated with soil and plants, such as Methylobacterium and Sphingomonas, was observed in the suburban site. Furthermore, our data revealed a shift in the bacterial community structure, diversity, and abundance of total bacteria at a threshold of 1.1-µm diameter. Interestingly, we observed that Legionella spp., the causal agents of legionellosis in humans, were mainly detected in > 2.1 µm coarse particles. Our data indicate that local environmental factors including built environments could influence the outdoor airborne bacterial community at each site. These results provide a basis for understanding the size-resolved properties of bacterial community composition, diversity, and abundance in outdoor aerosol samples and their potential influence on human health. [ABSTRACT FROM AUTHOR]