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We establish two results on three-dimensional del Pezzo fibrations in positive characteristic. First, we give an explicit bound for torsion index of relatively torsion line bundles. Second, we show the existence of purely inseparable sections with explicit bounded degree. To prove these results, we study log del Pezzo surfaces defined over imperfect fields.

PurposeThe risk factors for postoperative Hirschsprung-associated enterocolitis (HAEC) are still incompletely understood, especially age at which surgery is performed. Therefore, the aim of this study was to identify the risk factors for the development of postoperative HAEC in children operated during infancy.MethodsThirty-five children who had undergone radical surgery for Hirschsprung disease (HD) during infancy were included in the study. They were divided into two groups; those who developed postoperative HAEC (HAEC, 14 patients) and those who did not (no HAEC, 21 patients). Their medical records were retrospectively reviewed for clinical details.ResultsDeveloping postoperative HAEC was significantly associated with long-segment HD (p = 0.020) and the age at radical surgery (p = 0.0241). No other factors had a significant association with postoperative HAEC. In the patients who developed postoperative HAEC (n = 14), those with Trisomy 21 had significantly longer hospitalizations than those without. Patients with long-segment HD had a higher hospitalization rate than those with short-segment HD.ConclusionThis study clearly showed that long-segment HD and older age at radical surgery are risk factors for developing postoperative HAEC.

Let k be an algebraically closed field of characteristic $p>0$ . Let X be a normal projective surface over k with canonical singularities whose anticanonical divisor is nef and big. We prove that X is globally F-regular except for the following cases: (1) $K_X^2=4$ and $p=2$ , (2) $K_X^2=3$ and $p \\in \\{2, 3\\}$ , (3) $K_X^2=2$ and $p \\in \\{2, 3\\}$ , (4) $K_X^2=1$ and $p \\in \\{2, 3, 5\\}$ . For each degree $K_X^2$ , the assumption of p is optimal.

We show that any Kawamata log terminal del Pezzo surface over an algebraically closed field of large characteristic is globally$F$-regular or it admits a log resolution which lifts to characteristic zero. As a consequence, we prove the Kawamata–Viehweg vanishing theorem for klt del Pezzo surfaces of large characteristic.

Studying the genetic regulation of protein expression (through protein quantitative trait loci (pQTLs)) offers a deeper understanding of regulatory variants uncharacterized by mRNA expression regulation (expression QTLs (eQTLs)) studies. Here we report cis -eQTL and cis -pQTL statistical fine-mapping from 1,405 genotyped samples with blood mRNA and 2,932 plasma samples of protein expression, as part of the Japan COVID-19 Task Force (JCTF). Fine-mapped eQTLs ( n  = 3,464) were enriched for 932 variants validated with a massively parallel reporter assay. Fine-mapped pQTLs ( n  = 582) were enriched for missense variations on structured and extracellular domains, although the possibility of epitope-binding artifacts remains. Trans -eQTL and trans -pQTL analysis highlighted associations of class I HLA allele variation with KIR genes. We contrast the multi-tissue origin of plasma protein with blood mRNA, contributing to the limited colocalization level, distinct regulatory mechanisms and trait relevance of eQTLs and pQTLs. We report a negative correlation between ABO mRNA and protein expression because of linkage disequilibrium between distinct nearby eQTLs and pQTLs. Statistical fine-mapping of mRNA and protein quantitative trait loci in blood samples from the Japan COVID-19 Task Force sheds light on regulatory mechanisms and disease associations.

Acquired loss of hypothalamic orexin (hypocretin)-producing neurons causes the chronic sleep disorder narcolepsy-cataplexy. Orexin replacement therapy using orexin receptor agonists is expected as a mechanistic treatment for narcolepsy. Orexins act on two receptor subtypes, OX1R and OX2R, the latter being more strongly implicated in sleep/wake regulation. However, it has been unclear whether the activation of only OX2R, or both OX1R and OX2R, is required to replace the endogenous orexin functions in the brain. In the present study, we examined whether the selective activation of OX2R is sufficient to rescue the phenotype of cataplexy and sleep/wake fragmentation in orexin knockout mice. Intracerebroventricular [Ala 11 , D -Leu 15 ]-orexin-B, a peptidic OX2R-selective agonist, selectively activated OX2R-expressing histaminergic neurons in vivo, whereas intracerebroventricular orexin-A, an OX1R/OX2R non-selective agonist, additionally activated OX1R-positive noradrenergic neurons in vivo. Administration of [Ala 11 , D -Leu 15 ]-orexin-B extended wake time, reduced state transition frequency between wake and NREM sleep, and reduced the number of cataplexy-like episodes, to the same degree as compared with orexin-A. Furthermore, intracerebroventricular orexin-A but not [Ala 11 , D -Leu 15 ]-orexin-B induced drug-seeking behaviors in a dose-dependent manner in wild-type mice, suggesting that OX2R-selective agonism has a lower propensity for reinforcing/drug-seeking effects. Collectively, these findings provide a proof-of-concept for safer mechanistic treatment of narcolepsy-cataplexy through OX2R-selective agonism.

For a regular del Pezzo surface X , we prove that | - 12 K X | is very ample. Furthermore, we also give an explicit upper bound for the volume K X 2 which depends only on [ k : k p ] for the base field k . As a consequence, we obtain the boundedness of geometrically integral regular del Pezzo surfaces.

Introduction Owing to several therapeutic advancements, more patients with biliary atresia now survive into adulthood while retaining their native liver. However, the optimal strategy for long-term management of such patients remains unclear. Methods Aiming to establish the current management strategies, we reviewed previous reports of long-term outcome of BA who underwent surgery at our institution as well as the relevant literature, focusing particularly on the treatment of late complications. Results Approximately 30–40% of long-term survivors of biliary atresia who retain their native liver exhibit late sequelae such as cholangitis and portal hypertension. Early and appropriate intervention with Kasai portoenterostomy is essential for ensuring long-term survival with good quality of life. In our hospital, the current standard for Kasai portoenterostomy involves dissecting the fibrous remnants along the porta hepatis, just on the level of the liver capsule. Cholangitis is an important late complication in biliary atresia, and the possibility of mechanical obstruction of the biliary drainage route or deformity of the intrahepatic bile ducts with or without gallstones should be thoroughly evaluated in patients with intractable cholangitis. Regarding portal hypertension, appropriate interventions such as endoscopic variceal treatment and partial splenic embolization are considered to provide good quality of life when hepatic function is preserved. Conclusion Appropriate therapeutic management is strongly recommended in selected patients with late complications.