Real-world efficacy of proactive maintenance treatment with delgocitinib ointment twice weekly in adult patients with atopic dermatitis.

Previous studies have shown the efficacy of delgocitinib (DEL) ointment, a topical Janus kinase inhibitor, against atopic dermatitis (AD). However, there is no available information regarding the efficacy of DEL ointment in maintaining remission. Data of patients with AD who received remission maintenance therapy twice weekly with DEL or topical corticosteroid (TCS) on the affected skin of each upper limb were extracted from the medical records. Efficacy was assessed based on changes in pruritus numerical rating scale (NRS) score, stratum corneum hydration (SCH), erythema index (EI). Of 25 patients, four patients (16%) had eczema flare-ups on the TCS side and eight patients (32%) on the DEL side. The extent of change in each parameter between TCS- and DEL-treated areas of the skin did not differ significantly. The mean changes in the NRS and EI showed a slight improvement on the side treated with TCS and were slightly worse on the side treated with DEL. However, the SCH of the DEL group was maintained, while that of the TCS group worsened. TCS is more likely to be effective than DEL in terms of remission maintenance therapy. However, topical DEL is as effective as topical steroid in the maintenance therapy of AD in dry skin patients.

Evaluation of the resistance effect of QTLs derived from wild soybean (Glycine soja) to common cutworm (Spodoptera litura Fabricius).

Common cutworm (CCW) is a serious herbivorous insect pest of soybean. Previously, we conducted an antixenosis bioassay (measuring feeding preference) with CCW using recombinant inbred lines (RILs) derived from a cross between a wild soybean (Glycine soja) collected in Hiroshima prefecture (JP110755) and the leading cultivar, Fukuyutaka. The analysis revealed quantitative trait loci (QTLs) for antixenosis resistance, qRslx3 and qRslx4. In the present study we developed another RIL population using Fukuyutaka and a different G. soja, collected in Kumamoto prefecture (G406). An analysis revealed an antixenosis resistance QTL on chromosome 7, and the resistant allele of the QTL was derived from G406. The chromosomal position of the QTL was almost the same as that of CCW-2, a previously-reported antibiosis resistance QTL for CCW, detected in a F2 population derived from a cross between Fukuyutaka and a resistant cultivar Himeshirazu. These QTLs could be the same locus; however, G406 and Himeshirazu are likely to possess different alleles, because Himeshirazu allele exhibits no antixenosis effect. We expect that pyramiding of the resistance QTLs derived from G. soja will contribute to the development of CCW resistant cultivars.

Erratum: Quantitative trait loci associated with short inter-node length in soybean.

[This corrects the article on p. 554 in vol. 68, PMID: 30697116.].

Minimally Invasive Salvage Operations for Esophageal Cancer after Definitive Chemoradiotherapy.

BACKGROUND/AIMS: Because salvage surgery after definitive chemoradiotherapy for esophageal cancer is associated with high postoperative mortality and morbidity, minimally invasive methods are desirable. We analyzed the validity of minimally invasive salvage operations (MISO). METHODS: Twenty-five patients underwent salvage operation between 2010 and 2016 in our institution, 10 having undergone right transthoracic salvage esophagectomy (TTSE group), 6 transhiatal salvage esophagectomy (THSE), 6 salvage lymphadenectomy (SLA), and 3 salvage endoscopic submucosal dissection (SESD). Patients who had undergone THSE, SLA, or SESD were categorized as the MISO group. Short- and long-term outcomes were assessed. RESULTS: The mean duration of surgery was significantly shorter in the SLA groups than in the TTSE group (p = 0.0248). Blood loss was significantly less in the SLA than the TTSE group (p = 0.0340). Intensive care unit stay was shorter in the THSE than the TTSE group (p = 0.0412). There was no significant difference in postoperative mortality between the MISO and THSE groups. Postoperative hospital stay was significantly shorter in the SLA than the TTSE group (p = 0.0061). Patients' survivals did not differ significantly between the MISO and TTSE groups (p = 0.752). Multivariate analysis revealed that residual disease (R0; HR 4.872, 95% CI 1.387-17.110, p = 0.013) was the only independent factor influencing overall survival. CONCLUSION: MISO is preferable because short-term outcomes are better and long-term outcomes do not differ from those of TTSE.

Quantitative trait loci associated with short inter-node length in soybean.

Manipulating the genetic control of plant height is essential in soybean breeding to increase yield through the enlargement of the plant size while preventing lodging. A Japanese soybean germplasm, Y2, has distinctively shorter inter-node lengths than those of recently developed Japanese cultivars and is expected to provide new variation to prevent lodging. A quantitative trait loci (QTL) analysis for plant height-related traits was conducted using F2 individuals derived from a cross between the elite Japanese cultivar Fukuyutaka and Y2. A major QTL for average inter-node length (AIL) and plant height was identified on chromosome 13 and named qSI13-1 (QTL for short inter-node on chromosome 13). The Y2 allele of qSI13-1 was partially dominant for plant height. qSI13-1 exhibited no effect on either days to flowering or number of main stem nodes. The AILs and plant heights of the near-isogenic lines containing the Y2 allele of qSI13-1 in the genetic background of Fukuyutaka were significantly less than those of Fukuyutaka. No significant differences between the near-isogenic lines and Fukuyutaka were observed for seed yield and flowering date, indicating that qSI13-1 will be useful in developing cultivars with short plant heights without having negative effects on yield potential and days to flowering.

The isoflavone fraction from soybean presents mRNA maturation inhibition activity.

Recent findings indicate that mRNA splicing inhibitors can be potential anticancer candidates. We have previously established a screening system which monitors mRNA processing in order to identify mRNA processing inhibitors. Among a number of dietary resources, isoflavone fractions showed an inhibitory effect of mRNA processing. These findings demonstrate that a variety of dietary sources have an impact on mRNA biogenesis.

Involvement of MAK-1 and MAK-2 MAP kinases in cell wall integrity in Neurospora crassa.

Among three MAPK disruptants of Neurospora crassa, Δmak-1 was sensitive and Δmak-2 was hypersensitive to micafungin, a beta-1,3-glucan synthase inhibitor, than the wild-type or Δos-2 strains. We identified six micafungin-inducible genes that are involved in cell wall integrity (CWI) and found that MAK-1 regulated the transcription of non-anchored cell wall protein gene, ncw-1, and the beta-1,3-endoglucanase gene, bgt-2, whereas MAK-2 controlled the expression of the glycosylhydrolase-like protein gene, gh76-5, and the C4-dicarboxylate transporter gene, tdt-1. Western blotting analysis revealed that, in the wild-type strain, MAK-1 was constitutively phosphorylated from conidial germination to hyphal development. In contrast, the phosphorylation of MAK-2 was growth phase-dependent, and micafungin induced the phosphorylation of unphosphorylated MAK-2. It should be noted that the phosphorylation of MAK-1 was virtually abolished in the Δmak-2 strain, but was significantly induced by micafungin, suggesting functional cross talk between MAK-1 and MAK-2 signalling pathway in CWI.

Soybean extracts increase cell surface ZIP4 abundance and cellular zinc levels: a potential novel strategy to enhance zinc absorption by ZIP4 targeting.

Dietary zinc deficiency puts human health at risk, so we explored strategies for enhancing zinc absorption. In the small intestine, the zinc transporter ZIP4 functions as an essential component of zinc absorption. Overexpression of ZIP4 protein increases zinc uptake and thereby cellular zinc levels, suggesting that food components with the ability to increase ZIP4 could potentially enhance zinc absorption via the intestine. In the present study, we used mouse Hepa cells, which regulate mouse Zip4 (mZip4) in a manner indistinguishable from that in intestinal enterocytes, to screen for suitable food components that can increase the abundance of ZIP4. Using this ZIP4-targeting strategy, two such soybean extracts were identified that were specifically able to decrease mZip4 endocytosis in response to zinc. These soybean extracts also effectively increased the abundance of apically localized mZip4 in transfected polarized Caco2 and Madin-Darby canine kidney cells and, moreover, two apically localized mZip4 acrodermatitis enteropathica mutants. Soybean components were purified from one extract and soyasaponin Bb was identified as an active component that increased both mZip4 protein abundance and zinc levels in Hepa cells. Finally, we confirmed that soyasaponin Bb is capable of enhancing cell surface endogenous human ZIP4 in human cells. Our results suggest that ZIP4 targeting may represent a new strategy to improve zinc absorption in humans.

Multicenter randomized controlled study to assess the effect of prophylactic clipping on post-polypectomy delayed bleeding.

BACKGROUND AND AIM: Prophylactic clipping has been widely used to prevent post-procedural bleeding in colon polypctomy. However, its efficiency has not been confirmed and there is no consensus on the usefulness of prophylactic clipping. The aim of the present study was to evaluate the preventive effect of prophylactic clipping on post-polypectomy bleeding. METHODS: A multicenter randomized controlled study was conducted from January 2012 to July 2013 in Japan. Patients who had polyps <2 cm in diameter were divided into a clipping group and a non-clipping group by cluster randomization. After endoscopic polypectomy, patients allocated to the clipping group underwent prophylactic clipping, whereas the procedure was completed without clipping in patients allocated to the non-clipping group. Occurrence of post-polypectomy bleeding was compared between the two groups. RESULTS: Seven hospitals participated in this study. A total of 3365 polyps in 1499 patients were evaluated. The clipping group consisted of 1636 polyps in 752 patients, and the non-clipping group consisted of 1729 polyps in 747 patients. Post-polypectomy bleeding occurred in 1.10% (18/1636) of the cases in the clipping group, and in 0.87% (15/1729) of those in the non-clipping group. The difference was -0.22% (95% confidence interval [CI]: -0.96, 0.53). Upper limit of the 95% CI was lower than the non-inferiority margin (1.5%), and we could thus prove non-inferiority of non-clipping against clipping. CONCLUSION: Prophylactic clipping is not necessary to prevent post-polypectomy bleeding for polyps <2 cm in diameter.

Multicenter study on hemorrhagic risk of heparin bridging therapy for periendoscopic thromboprophylaxis.

BACKGROUND: For endoscopic interventions, heparin bridging therapy is recommended in patients who are at high risk from interruption of antithrombotic therapy. Although heparin bridging has been reported to be effective in preventing thrombosis, several reports have raised concerns about increased risk of bleeding. The aim of this study was to clarify complications of hepari bridging therapy in therapeutic endoscopy. METHODS: A nationwide multicenter survey using questionnaire was performed about patients undergoing therapeutic endoscopy with heparin bridging. Patients who underwent therapeutic endoscopy without heparin bridging therapy were considered as controls. Compliance scores of heparin bridging therapy guideline were employed, and association was analyzed between the score and occurrence of post-procedural bleeding. RESULTS: The incidence of post-procedural bleeding was significantly higher (13.5%, 33/245) in the heparin group compared with the control group (2.7%, 299/11102)(p < 0.001). Thrombosis occurred in 1 patient each in the two groups. In the heparin group, post-procedural bleeding was more likely to be delayed bleeding. Dose adjustment of heparin was a significant factor contributing to bleeding. The compliance score of heparin bridging therapy guideline was significantly higher in those who suffered bleeding. CONCLUSIONS: Heparin bridging therapy significantly increased the risk of post-procedural bleeding compared with the control. The bleeding risk was associated with greater adherence with guidelines for heparin bridging therapy.

A thaumatin-like protein, Rj4, controls nodule symbiotic specificity in soybean.

Soybeans exhibit a nitrogen-fixing symbiosis with soil bacteria of the genera Bradyrhizobium and Ensifer/Sinorhizobium in a unique organ, the root nodule. It is well known that nodulation of soybean is controlled by several host genes referred to as Rj (rj) genes. Among these genes, a dominant allele, Rj4, restricts nodulation with specific bacterial strains such as B. elkanii USDA61 and B. japonicum Is-34. These incompatible strains fail to invade the host epidermal cells as revealed by observations using DsRed-labeled bacteria. Here, we describe the molecular identification of the Rj4 gene by using map-based cloning with several mapping populations. The Rj4 gene encoded a thaumatin-like protein (TLP) that belongs to pathogenesis-related (PR) protein family 5. In rj4/rj4 genotype soybeans and wild soybeans, we found six missense mutations and two consecutive amino acid deletions in the rj4 gene as compared with the Rj4 allele. We also found, using hairy root transformation, that the rj4/rj4 genotype soybeans were fully complemented by the expression of the Rj4 gene. Whereas the expression of many TLPs and other PR proteins is induced by biotic/abiotic stress, Rj4 gene expression appears to be constitutive in roots including root nodules.

Endoscopic diagnosis of early neoplasia of the esophagus with narrow band imaging: correlations among background coloration and iodine staining findings.

BACKGROUND AND AIM: It was previously reported that high-grade intraepithelial neoplasia of the esophagus turns pink within a few minutes after iodine staining (pink-color sign; PCS); however, iodine staining is uncomfortable. By using narrow band imaging (NBI), color change in the area between the intraepithelial papillary capillary loop (background coloration; BGC) is often observed within the brownish area. The diagnostic usefulness of BGC findings for differentiating high-grade intraepithelial neoplasia from low-grade intraepithelial neoplasia was evaluated. METHODS: In a prospective observational study from September 2010 to August 2012, 285 patients who were in a high-risk group for esophageal squamous cell carcinoma underwent endoscopic examination. Lesions with both endoscopic findings of dilated intraepithelial papillary capillary loop on NBI and iodine-unstained areas were studied, in which endoscopic biopsy or endoscopic resection was subsequently performed. The esophageal background mucosa was also evaluated on the basis of the iodine staining pattern (uniform type: Group U, scattered type: Group S). RESULTS: One hundred three esophageal lesions in 87 patients were studied. When BGC was used as the differentiation index, sensitivity was 93.8%, specificity was 88.2%, and accuracy was 91.3%. When PCS was used, sensitivity was 97.9%, specificity was 88.2%, and accuracy was 93.2% (P = 0.79). In Group U (n = 54), BGC had an accuracy of 93.8%, and PCS had an accuracy of 92.3% (P = 1.0). On the other hand, in Group S (n = 33), BGC had an accuracy of 86.8%, while PCS had an accuracy of 94.7% (P = 0.27). CONCLUSIONS: Diagnosis using BGC on NBI may substitute for diagnosis based on PCS in many patients.

Effectiveness of sternocleidomastoid flap repair for cervical anastomotic leakage after esophageal reconstruction.

BACKGROUND/AIMS: The purpose of this study was to investigate the effectiveness of sternocleidomastoid (SCM) flap repair for anastomotic leakage after esophagectomy. METHODS: A refractory cutaneous fistula from the gastric stump developed in 8 patients with esophageal cancer who underwent esophagogastric anastomosis after esophagectomy. All patients underwent SCM flap repair. The cutaneous fistula was removed and resutured. The sternal head of the left SCM was dissected from the manubrium of the sternum and sutured onto the repaired gastric stump. RESULTS: The operative duration was 80-220 min (median, 120 min). The amount of intraoperative bleeding ranged from 5 to 182 g (median, 15 g). The absence of recurrent anastomotic leakage was confirmed after the SCM flap repair in every patient. Oral intake was initiated 7-15 days (median, 10 days) after the repair operation without discomfort. CONCLUSIONS: SCM flap repair is an effective and minimally invasive treatment method for cervical anastomotic leakage after esophageal reconstruction. This method may be considered in patients with refractory leakage of the gastric stump after staple anastomosis.

Bony Surface-Matching Registration of Neuronavigation with Sectioned 3-Dimensional Skull in Prone Position.

BACKGROUND: Neuronavigation has become an essential system for brain tumor resections. It is sometimes difficult to obtain accurate registration of the neuronavigation with the patient in the prone position. Bony surface-matching registration should be more precise than skin surface-matching registration; however, it is difficult to establish bony registration with limited exposed bone. We created a new bony surface-matching method to a sectioned 3-dimensional (3D) virtual skull in a neuronavigation system and registered with a sectioned 3D skull. In this study, the bony surface-matching with sectioned 3D registration is applied to provide precise registration for brain tumor resection in the prone position. METHODS: From May 2023 to April 2024, 17 patients who underwent brain tumor resection in the prone position were enrolled. The navigation system StealthStation S8 (Medtronic, Dublin, Ireland) was used. Bony surface-matching registration with a whole 3D skull in a neuronavigation system was performed. Next, a sectioned 3D skull was made according to the surgical location to compare with the whole 3D skull registration. A phantom model was also used to validate the whole and sectioned 3D skull registration. RESULTS: Whole 3D skull registration was successful for only 2 patients (11.8%). However, sectioned 3D skull registration was successful for 16 patients (94.1%). The examinations with a phantom skull model also showed superiority of sectioned 3D skull registration to whole 3D skull registration. CONCLUSIONS: Sectioned 3D skull registration was superior to whole 3D skull registration. The sectioned 3D skull method could provide accurate registration with limited exposed bone.

Deletion and expression analysis of beta-(1,3)-glucanosyltransferase genes in Neurospora crassa.

GPI(glycosylphosphatidylinositol)-anchored beta-(1,3)-glucanosyltransferases play an active role in cell wall biosynthesis in fungi. Neurospora crassa has 5 putative beta-(1,3)-glucanosyltransferase genes, namely, gel-1, gel-2, gel-3, gel-4, and gel-5, in its genome. Among them, the gel-3 gene is constitutively expressed at the highest level in growing hyphae, whereas gel-1 is expressed at the lowest level. The gel-3 deletion mutant displayed slow growth, while other gel gene disruptants exhibited normal growth. Although no gel gene disruption affected pH sensitivity and fertility, all Δgel mutants were resistant to cell wall degradation enzymes. Micafungin, a beta-(1,3)-glucan synthase inhibitor, induced gel-4 expression in the wild-type and 2 MAP kinase mutants mak-1 and mak-2 strains. In contrast, fludioxonil, an activator of OS-2 MAP kinase, strongly induced the gel-1 gene in the wild-type strain. Its induction was nearly abolished in the os-2 and in the atf-1/asl-1 mutant. These suggested that GEL-3 is a major factor in mycelial growth, while GEL-1 and GEL-4 may play important roles in cell wall remodeling in response to stress conditions or cell wall damage, respectively.

Endoscopic in vivo cellular imaging of superficial squamous cell carcinoma of the head and neck by using an integrated endocytoscopy system (with video).

BACKGROUND: Recently, some patients have been found to have superficial squamous cell carcinoma (SCC) of the head and neck region during GI endoscopy; however, endoscopic biopsy from a lesion in the head and neck region is troublesome. An endocytoscopy system has been reported to enable optical biopsy of an esophageal lesion. OBJECTIVE: To evaluate the feasibility of in vivo cellular imaging with an integrated endocytoscopy system for patients with superficial SCC of the head and neck. DESIGN: Experimental pilot study. SETTING: University hospital. PATIENTS: This study involved 12 patients who were found to have superficial SCC of the head and neck during GI endoscopy. INTERVENTION: Endocytoscopic images were taken of each lesion and of the surrounding mucosa. The images were later reviewed by 1 pathologist and 2 endoscopists who were unaware of any other findings. MAIN OUTCOME MEASUREMENTS: Correlation between endocytoscopy diagnosis and histologic diagnosis. RESULTS: Adequate endocytoscopic images could be obtained in 11 of the 12 patients (15 of 16 lesions). For endocytoscopic images of 15 lesions and 12 areas of surrounding mucosa, the overall accuracy of endocytoscopic diagnosis in differentiating between nonmalignant and malignant histopathology by the pathologist, endoscopist 1, and endoscopist 2 were 96%, 96%, and 96%, respectively. The kappa value for interobserver agreement was 0.77. LIMITATIONS: Single-center experience, small number of patients. CONCLUSION: An endocytoscopy system has the potential to be used as an optical biopsy for superficial head and neck lesions.

Identification of a high risk gastric cancer group using serum pepsinogen after successful eradication of Helicobacter pylori.

BACKGROUND AND AIM: Pepsinogen (PG) method is widely used to identify high risk groups of gastric cancer. It is very useful before Helicobacter pylori eradication, but after eradication the method becomes useless because the PGI, PGII, PGI/II ratios change. Therefore, we aimed to identify a high risk group for gastric cancer using serum pepsinogen after successful eradication of H. pylori. METHODS: A total of 261 participants were enrolled after successful eradication of H. pylori in Hokkaido University Hospital from 1995 to 2010. Participants with renal failure, taking proton pump inhibitors, and those with advanced gastric cancer were excluded. Serum levels of PGI and II were measured using chemiluminescent immunoassay method. RESULTS: Receiver operating characteristic curves using cancerous and non-cancerous data in post-eradication determined the optimal cut-off value of PGI/II as 4.5. The sensitivity and the specificity were 65.9% and 79.3%, respectively. The usual PG method includes 48.9% of cancer cases, and the PGI/II ≤ 4.5 in post-eradication includes 65.9% of them, and it includes approximately half of the high risk group of diffuse type cancer. PGI/II ≤ 4.5 in post-eradication included many gastric cancer cases detected after eradication (12/16 = 75%). CONCLUSION: In the identification of a high risk group for gastric cancer, we suggest that the optimal cut-off value of PGI/II after successful eradication of H. pylori is 4.5. PGI/II ≤ 4.5 in post-eradication includes more gastric cancer cases compared with the traditional PG method, and 75% of gastric cancer cases detected after eradication.

CD24 expression is associated with progression of gastric cancer.

BACKGROUND/AIMS: Mortality rates due to gastric cancer are high in Japan. To improve patient prognosis, new biomarkers for diagnosis and treatment are urgently required. In this study we investigated the role of CD24, a cell adhesion glycoprotein implicated in tumor cell proliferation, which is used as a prognostic marker in various cancers. METHODOLOGY: We analyzed CD24 expression in 173 gastric adenocarcinomas by immunohistochemistry and compared the data with clinicopathological parameters and patient overall survival. Furthermore, we performed Western blotting analysis of CD24 in six human gastric adenocarcinoma cell lines, Kato III, MKN1, MKN28, MKN45, MKN74, and HGC-27. RESULTS: CD24 up-regulation was significantly correlated with depth of invasion (p=0.005) and pathological high stages (p=0.043). We observed a relationship between high CD24 expression and lymph node metastasis, venous invasion and lymphatic invasion. CD24 expression tended to be higher in cell lines derived from differentiated gastric carcinoma, including those derived from lymph node metastasis. CONCLUSIONS: Our study suggests that gastric cancer patients with high CD24 expression should be closely monitored for recurrence following resections. CD24 expression is a potential biomarker for gastric cancer prognosis and provides a new molecular target for therapeutic strategies.

Endoscopic resection (endoscopic mucosal resection/ endoscopic submucosal dissection) for superficial esophageal squamous cell carcinoma: current status of various techniques.

Endoscopic resection (ER) has been widely accepted as an effective and minimally invasive treatment for patients with superficial esophageal squamous cell carcinoma (SCC). Techniques of conventional endoscopic mucosal resection (EMR) were first developed for ER. There are three representative methods of conventional EMR: endoscopic esophageal mucosal resection (EEMR)-tube method, EMR using a cap-fitted endoscope (EMRC) method and two-channel EMR method. In the past decade, techniques of endoscopic submucosal dissection (ESD) have become established as standard methods of ER. ESD allows en bloc resection of a lesion, irrespective of the size and shape of the lesion. Recently, results of retrospective cohort studies confirming that ESD is superior to EMR as a curative treatment for superficial esophageal SCC have been reported. Representative knives that are now frequently used in esophageal ESD include Hook knife, Triangle tip knife, IT knife nano, Flush knife-BT, Dual knife, SB knife, and so on. Although there are various knives developed for ESD, the basic techniques for safe and effective ESD are the same.