Dose compliance of estramustine phosphate in neoadjuvant chemohormonal therapy combined with degarelix acetate predicts the biochemical recurrence in patients with very high-risk prostate cancer who underwent robot-assisted radical prostatectomy.

OBJECTIVES: The objective of this study is to evaluate the safety and efficacy of neoadjuvant degarelix acetate and low-dose estramustine phosphate for high-/very high-risk prostate cancer. METHODS: Overall, 187 patients diagnosed with National Comprehensive Cancer Network high-/very high-risk cTanyN0M0 localized prostate cancer who consented to undergo robot-assisted radical prostatectomy after receiving neoadjuvant chemohormonal therapy for 6 months were prospectively enrolled between December 2017 and March 2023. Adverse events, perioperative and histopathological outcomes, and biochemical recurrence-free survival rates were examined. Survival analysis compared the estramustine phosphate completion and reduction groups. RESULTS: Thirty-six patients discontinued neoadjuvant therapy in <5 months owing to adverse events (n = 34) or other reasons (n = 2). Eleven were excluded for being in the postoperative castration range. Of the 140 patients who underwent surgery, 124 continued with two tablets of estramustine phosphate and 16 with one tablet. Overall, 82 patients were very high-risk. Histopathological outcomes were significantly worse in the very high-risk group than those in the high-risk group. Very high-risk status and estramustine phosphate reduction were significant factors in biochemical recurrence in multivariate analysis. The biochemical recurrence-free survival rate in very high-risk patients was significantly lower in the estramustine phosphate dose reduction group than in the completion group but not significant in high-risk patients. Major adverse events were anemia (n = 174), elevated transaminase levels (n = 68), and deep vein thrombosis (n = 24). Severe adverse events included acute coronary syndrome (n = 4) and pulmonary embolism (n = 3). CONCLUSIONS: Dose compliance with estramustine phosphate predicted biochemical recurrence in patients with very high-risk prostate cancer undergoing robot-assisted radical prostatectomy with neoadjuvant chemohormonal therapy.

Identification of intracerebral hemorrhage in the early-phase of MM1+2C-type sporadic Creutzfeldt-Jakob disease: A case report.

We report a case of early-phase sporadic Creutzfeldt-Jakob disease (sCJD) complicated by intracerebral hemorrhage (ICH), classified as MM1 + 2C-type based on autopsy. A 61-year-old Japanese man presented to our hospital with speaking difficulties including repeated usage of the same words. He was hospitalized on the seventh day after symptom onset, and diffusion-weighted images on magnetic resonance imaging showed hyperintense regions in the frontal cortex and caudate nucleus. On the 11th day after symptom onset, head computed tomography revealed ICH in the right occipital and parietal lobes. Routine laboratory evaluations and angiography revealed no cause of ICH. Myoclonus of the extremities and drowsiness were observed on the 15th day after symptom onset. He reached the state of akinetic mutism approximately two months after symptom onset. The cerebrospinal fluid test revealed positive real-time quaking-induced conversion and 14-3-3 protein. Electroencephalography revealed periodic sharp wave complexes. A clinical diagnosis of probable Creutzfeldt-Jakob disease was made according to the diagnostic criteria. After a relapse of pneumonia, he passed away on the 103rd day after symptom onset. Postmortem examination revealed ICH in the right posterior cingulate gyrus. No pathological change that might have caused ICH was obtained. Although the effect of sCJD on the onset of ICH is undeniable, the cause of ICH was unknown. Prion protein immunohistochemistry revealed the following results: (1) weak synaptic-type deposits in the tissue rarefacted by ICH; (2) synaptic-type deposits in the cerebral cortex, which showed fine vacuoles; and (3) perivacuolar-type deposits in the inferior temporal gyrus and lingual gyrus, which showed frequent large confluent vacuoles. Although it could be considered MM1-type sCJD clinically, this case was neuropathologically diagnosed as having MM1 + 2C-type sCJD. It was shown that ICH may occur in early-phase sCJD. To improve sCJD prognosis, treatment of complications and careful follow up are important. Furthermore, pathological diagnosis is indispensable for sCJD type diagnosis.

Developing Heritable Mutations in Arabidopsis thaliana Using a Modified CRISPR/Cas9 Toolkit Comprising PAM-Altered Cas9 Variants and gRNAs.

Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9), comprising an RNA-guided DNA endonuclease and a programmable guide RNA (gRNA), is currently recognized to be a powerful genome-editing tool and is widely used in biological science. Despite the usefulness of the system, a protospacer-adjacent motif (PAM) immediately downstream of the target sequence needs to be taken into account in the design of the gRNA, a requirement which limits the flexibility of the CRISPR-based genome-editing system. To overcome this limitation, a Cas9 isolated from Streptococcus pyogenes, namely SpCas9, engineered to develop several variants of Cas9 nuclease, has been generated. SpCas9 recognizes the NGG sequence as the PAM, whereas its variants are capable of interacting with different PAMs. Despite the potential advantage of the Cas9 variants, their functionalities have not previously been tested in the widely used model plant, Arabidopsis thaliana. Here, we developed a plant-specific vector series harboring SpCas9-VQR (NGAN or NGNG) or SpCas9-EQR (NGAG) and evaluated their functionalities. These modified Cas9 nucleases efficiently introduced mutations into the CLV3 and AS1 target genes using gRNAs that were compatible with atypical PAMs. Furthermore, the generated mutations were passed on to their offspring. This study illustrated the usefulness of the SpCas9 variants because the ability to generate heritable mutations will be of great benefit in molecular genetic analyses. A greater number of potential SpCas9-variant-recognition sites in these genes are predicted, compared with those of conventional SpCas9. These results demonstrated the usefulness of the SpCas9 variants for genome editing in the field of plant science research.

Occludin induces microvillus formation via phosphorylation of ezrin in a mouse hepatic cell line.

Apical and basolateral cell membranes are separated by tight junctions (TJs). Microvilli are limited to the apical cell membrane. TJs and microvilli are the landmarks for epithelial cell polarity. However, the direct relationship between TJ proteins (TJPs) and the components of microvilli remains unclear. In this study, we investigated whether occludin, which is considered to be a functional TJP, is involved in microvillus formation. In occludin knockout mouse hepatic cells (OcKO cells), the microvillus density was less than that in wild-type (WT) cells and the length of microvilli was short. Immunoreactivity of ezrin was decreased in OcKO cells compared with that in WT cells. Although there was no change in the expression level of ezrin, phosphorylation of ezrin was decreased in OcKO cells. The microvillus density and the length of microvilli were increased in OcKO cells by transfection of full-length mouse occludin and COOH-terminal domains of occludin. These results suggested that occludin induced microvillus formation via phosphorylation of ezrin and that the COOH-terminal domain of occludin, which is localized in non-TJ areas, might be able to induce microvilli formation. Our results provide new insights into the function of occludin.

Metagenomic study of endophytic bacterial community of sweet potato (Ipomoea batatas) cultivated in different soil and climatic conditions.

The aim of this study was to clarify effects of soil and climatic conditions on community structure of sweet potato bacterial endophytes by applying locked nucleic acid oligonucleotide-PCR clamping technique and metagenomic analysis. For this purpose, the soil samples in three locations were transferred each other and sweet potato nursery plants from the same farm were cultivated for ca. 3 months. After removal of plastid, mitochondria and undefined sequences, the averaged numbers of retained sequences and operational taxonomic units per sample were 20,891 and 846, respectively. Proteobacteria (85.0%), Bacteroidetes (6.6%) and Actinobacteria (6.3%) were the three most dominant phyla, accounting for 97.9% of the reads, and γ-Proteobacteria (66.3%) being the most abundant. Top 10 genera represented 81.2% of the overall reads in which Pseudomonas (31.9-45.0%) being the most predominant. The overall endophytic bacterial communities were similar among the samples which indicated that the soil and the climatic conditions did not considerably affect the entire endophytic community. The original endophytic bacterial community might be kept during the cultivation period.

C1q/TNF-related protein 3 expression and effects on adipocyte differentiation of 3T3-L1 cells.

Adipose tissue-derived adipokines influence a number of organs critical for energy homeostasis and metabolism. One of the most extensively studied adipokines is adiponectin, which exerts anti-diabetic, anti-inflammatory, and anti-atherogenic functions on various cell types. CTRP3, a paralog of adiponectin, is a member of the C1q and tumor necrosis factor-related protein (CTRP) superfamily. CTRP3 reduces hepatic triglyceride levels in diet-induced obese (DIO) mice. However, the physiological role of CTRP3 in adipocytes is largely unknown. In the course of our investigation of expression profiles of CTRPs during adipocyte differentiation, we found that CTRP3 expression pattern is different from that previously reported. Therefore, we examined the effect of CTRP3 on adipogenesis using 3T3-L1 cells. The expression level of CTRP3 was markedly decreased during the differentiation of 3T3-L1 cells. Recombinant CTRP3 (rCTRP3) treatment significantly reduced intracellular lipid content and decreased expression of adipogenic marker genes such as peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein alpha (C/EBPα), adiponectin, and fatty acid binding protein 4 (FABP4) in 3T3-L1 cells. Furthermore, rCTRP3 induced the phosphorylation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and Akt in differentiated 3T3-L1 adipocytes. These results suggest that CTRP3 may negatively regulate lipid metabolism during adipocyte differentiation.

Inferior Mesenteric Artery Aneurysm Complicated With Occluded Celiac and Superior Mesenteric Artery After Replacement of Thoracoabdominal Aorta for Chronic Dissected Thoracoabdominal Aortic Aneurysm.

We report a case of inferior mesenteric artery aneurysm (IMAA) after the replacement of the thoracoabdominal aorta for a chronic dissected thoracoabdominal aortic aneurysm in which the celiac artery and superior mesenteric artery were occluded. We performed the resection of the IMAA and the revascularization of the superior mesenteric artery, inferior mesenteric artery, and meandering artery. The patient's postoperative course was uneventful, without bowel ischemia. From the findings of intraoperative flow measurement of the visceral arteries, revascularization of the superior mesenteric artery was judged to be appropriate in this situation.

Effects of Breathing-Based Meditation on Earthquake-Affected Health Professionals.

On March 11, 2013, the Great East Japan Earthquake (magnitude 9) hit the northern part of Japan (Tohoku), killing more than 15 000 people and leaving long-lasting scars, including psychological damage among evacuees, some of whom were health professionals. Little is known about meditation efficacy on disaster-affected health professionals. The present study investigated the effects of breathing-based meditation on seminar participants who were health professionals who had survived the earthquake. This study employed a mixed methods approach, using both survey data and handwritten qualitative data. Quantitative results of pre- and postmeditation practice indicated that all mood scales (anger, confusion, depression, fatigue, strain, and vigor) were significantly improved (N = 17). Qualitative results revealed several common themes (emancipation from chronic and bodily senses; holistic sense: transcending mind-body; re-turning an axis in life through reflection, self-control, and/or gratitude; meditation into mundane, everyday life; and coming out of pain in the aftermath of the earthquake) that had emerged as expressions of participant meditation experiences. Following the 45-minute meditation session, the present study participants reported improvements in all psychological states (anger, confusion, depression, fatigue, strain, and vigor) in the quantitative portion, which indicated efficacy of the meditation. Our analysis of the qualitative portion revealed what and how participants felt during meditating.

Human Cytosolic Sulfotransferase SULT1A3 Mediates the Sulfation of Dextrorphan.

Dextrorphan, an active metabolite of the antitussive dextromethorphan, has been shown to be subjected to sulfation by several zebrafish cytosolic sulfotransferases (SULTs). We were interested in finding out which of the human SULT(s) is(are) capable of catalyzing the sulfation of dextrorphan, and to verify whether sulfation of dextrorphan may occur in cultured human cells and human organ cytosols. Data from the enzymatic assays showed that, of all thirteen known human SULTs, SULT1A3 displayed the strongest dextrorphan-sulfating activity. Cell culture experiments using HepG2 human hepatoma cells and Caco-2 human colon carcinoma cells incubated with [(35)S]sulfate together with varying concentrations of dextrorphan revealed indeed the production and release of [(35)S]sulfated dextrorphan in a concentration-dependent manner. Additionally, significant dextrorphan-sulfating activity was detected in human liver, small intestine and lung cytosols. Taken together, these results provided a biochemical basis for the sulfation of dextrorphan in humans.

Evaluation of the reliability of the maximum entropy method for reconstructing 3D and 4D NOESY-type NMR spectra of proteins.

Despite their advantages in analysis, 4D NMR experiments are still infrequently used as a routine tool in protein NMR projects due to the long duration of the measurement and limited digital resolution. Recently, new acquisition techniques for speeding up multidimensional NMR experiments, such as nonlinear sampling, in combination with non-Fourier transform data processing methods have been proposed to be beneficial for 4D NMR experiments. Maximum entropy (MaxEnt) methods have been utilised for reconstructing nonlinearly sampled multi-dimensional NMR data. However, the artefacts arising from MaxEnt processing, particularly, in NOESY spectra have not yet been clearly assessed in comparison with other methods, such as quantitative maximum entropy, multidimensional decomposition, and compressed sensing. We compared MaxEnt with other methods in reconstructing 3D NOESY data acquired with variously reduced sparse sampling schedules and found that MaxEnt is robust, quick and competitive with other methods. Next, nonlinear sampling and MaxEnt processing were applied to 4D NOESY experiments, and the effect of the artefacts of MaxEnt was evaluated by calculating 3D structures from the NOE-derived distance restraints. Our results demonstrated that sufficiently converged and accurate structures (RMSD of 0.91Å to the mean and 1.36Å to the reference structures) were obtained even with NOESY spectra reconstructed from 1.6% randomly selected sampling points for indirect dimensions. This suggests that 3D MaxEnt processing in combination with nonlinear sampling schedules is still a useful and advantageous option for rapid acquisition of high-resolution 4D NOESY spectra of proteins.

[An ileal neobladder-enteric fistula 10 years after a radical cystectomy with ileal neobladder construction].

A 67-year-old male underwent a radical cystectomy and ileal neobladder construction in September 2002. He developed adhesive ileus postoperatively and underwent an intestine-ascending colon bypass operation with a side-to-side anastomosis in December of 2002. Subsequently, the patient developed ileus frequently, which improved with conservative management. In February 2013, he had fecaluria and was diagnosed with an ileal neobladder-enteric fistula based on computed tomography 2 hours after contrast medium injection. He underwent closure of the intestinal anal side of the anastomosis between the intestine and ascending colon. The fecaluria disappeared and he is making steady progress. An ileal neobladderenteric fistula as a long-term postoperative complication of ileal neobladder construction is extremely rare, with no other reports to our knowledge. Here, we discuss its cause, diagnosis and treatment, with reference to previous reports.

BERT4FCA: A method for bipartite link prediction using formal concept analysis and BERT.

Link prediction in bipartite networks finds practical applications in various domains, including friend recommendation in social networks and chemical reaction prediction in metabolic networks. Recent studies have highlighted the potential for link prediction by maximal bi-cliques, which is a structural feature within bipartite networks that can be extracted using formal concept analysis (FCA). Although previous FCA-based methods for bipartite link prediction have achieved good performance, they still have the problem that they cannot fully capture the information of maximal bi-cliques. To solve this problem, we propose a novel method for link prediction in bipartite networks, utilizing a BERT-like transformer encoder network to enhance the contribution of FCA to link prediction. Our method facilitates bipartite link prediction by learning more information from the maximal bi-cliques and their order relations extracted by FCA. Experimental results on five real-world bipartite networks demonstrate that our method outperforms previous FCA-based methods, a state-of-the-art Graph Neural Network(GNN)-based method, and classic methods such as matrix-factorization and node2vec.

Psoriasis vulgaris of the skin caused a L3-L4 lumbar epidural spinal abscess.

Background: In a 31-year-old male, psoriasis vulgaris (PV) of the skin caused paraparesis attributed to a L3-L4 epidural spinal abscess that required emergent surgical decompression. Case Description: A 31-year-old male presented with lower back pain and cauda equina compression attributed to a magnetic resonance-documented L34 enhancing lesion consistent with a spinal epidural abscess (SEA). The skin over the L3-L4 level revealed severe PV that proved to be the likely etiology of the right-sided paraspinal muscle abscess, infected right L3-L4 facet joint, and SEA. At surgery, the foci of infection were excised/decompressed, and cultures grew methicillin-susceptible Staphylococcus aureus. Following surgery, the patient was improved and was treated with appropriate antibiotic therapy. Conclusion: PV caused a L3-L4 epidural spinal abscess and cauda equina compression in a 31-year-old male who was successfully treated with operative decompression and appropriate antibiotic management.

Communicating hydrocephalus after resection of a meningioma ventral to the foramen magnum.

Background: Tumors in or near the foramen magnum may cause communicating or non-communicating hydrocephalus (HC), depending on their size and location. Here, an 81-year-old female developed communicating HC following the resection of a meningioma ventral to the foramen magnum. Case Description: An 81-year-old female presented with numbness in the left neck and left hemiparesis. The magnetic resonance revealed an 18-mm tumor ventral to the foramen magnum that significantly enlarged over the past 6 months. She underwent total tumor resection but then presented with progressive HC both clinically (i.e., instability of gait with confusion) and radiographically (computed tomography). Following placement of a lumboperitoneal (LP) shunt, symptoms markedly improved. Further, the cerebrospinal fluid (CSF) analysis showed elevated cell counts and protein concentrations, indicating likely "leakage" of intratumoral contents postoperatively contributing to the progressive HC. Conclusion: Patients presenting with acute meningiomas ventral to the foramen magnum may develop postoperative communicating HC attributed to tumor-related CSF leakage of necrotic intratumoral components that can be successfully treated with a LP shunt.

Totally retroperitoneal approach for robot-assisted nephroureterectomy with bladder cuff without repositioning.

INTRODUCTION: Robot-assisted nephroureterectomy (RANU) for upper urinary tract urothelial carcinoma is typically performed via the transperitoneal approach because of limited surgical space. However, a retroperitoneal approach may be preferable in patients with a history of abdominal surgery or in those in whom pelvic lymph node dissection is unnecessary. MATERIALS AND SURGICAL TECHNIQUES: RANU via the retroperitoneal approach was selected for two patients diagnosed with high-grade upper urothelial carcinoma with a history of abdominal surgery. Nephrectomy was performed in the 90° flank position, and the bed was tilted at 20°. The retroperitoneal space was extended, and the robot trocar was subsequently repositioned in the left lower quadrant. After redocking the robot, the distal ureter was dissected, and the bladder cuff was resected en bloc along with the kidney and the ureter. Neither patient had any complications within 3 months postoperatively. DISCUSSION: By devising a new technique for trocar placement, total retroperitoneal RANU without repositioning was possible, even in a small patient.

Awake surgery for a deaf patient using sign language: A case report.

Background: Although awake surgery is the gold standard for resecting brain tumors in eloquent regions, patients with hearing impairment require special consideration during intraoperative tasks. Case Description: We present a case of awake surgery using sign language in a 45-year-old right-handed native male patient with hearing impairment and a neoplastic lesion in the left frontal lobe, pars triangularis (suspected to be a low-grade glioma). The patient primarily communicated through sign language and writing but was able to speak at a sufficiently audible level through childhood training. Although the patient remained asymptomatic, the tumors gradually grew in size. Awake surgery was performed for tumors resection. After the craniotomy, the patient was awake, and brain function mapping was performed using tasks such as counting, picture naming, and reading. A sign language-proficient nurse facilitated communication using sign language and the patient vocally responded. Intraoperative tasks proceeded smoothly without speech arrest or verbal comprehension difficulties during electrical stimulation of the tumor-adjacent areas. Gross total tumor resection was achieved, and the patient exhibited no apparent complications. Pathological examination revealed a World Health Organization grade II oligodendroglioma with an isocitrate dehydrogenase one mutant and 1p 19q codeletion. Conclusion: Since the patient in this case had no dysphonia due to training from childhood, the task was presented in sign language, and the patient responded vocally, which enabled a safe operation. Regarding awake surgery in patients with hearing impairment, safe tumor resection can be achieved by performing intraoperative tasks depending on the degree of hearing impairment and dysphonia.

Genetic diversity and geographical distribution of indigenous soybean-nodulating bradyrhizobia in the United States.

We investigated the relationship between the genetic diversity of indigenous soybean-nodulating bradyrhizobia and their geographical distribution in the United States using nine soil isolates from eight states. The bradyrhizobia were inoculated on three soybean Rj genotypes (non-Rj, Rj(2)Rj(3), and Rj(4)). We analyzed their genetic diversity and community structure by means of restriction fragment length polymorphisms of PCR amplicons to target the 16S-23S rRNA gene internal transcribed spacer region, using 11 USDA Bradyrhizobium strains as reference strains. We also performed diversity analysis, multidimensional scaling analysis based on the Bray-Curtis index, and polar ordination analysis to describe the structure and geographical distribution of the soybean-nodulating bradyrhizobial community. The major clusters were Bradyrhizobium japonicum Bj123, in the northern United States, and Bradyrhizobium elkanii, in the middle to southern regions. Dominance of bradyrhizobia in a community was generally larger for the cluster belonging to B. elkanii than for the cluster belonging to B. japonicum. The indigenous American soybean-nodulating bradyrhizobial community structure was strongly correlated with latitude. Our results suggest that this community varies geographically.

Link prediction on bipartite networks using matrix factorization with negative sample selection.

We propose a new method for bipartite link prediction using matrix factorization with negative sample selection. Bipartite link prediction is a problem that aims to predict the missing links or relations in a bipartite network. One of the most popular solutions to the problem is via matrix factorization (MF), which performs well but requires reliable information on both absent and present network links as training samples. This, however, is sometimes unavailable since there is no ground truth for absent links. To solve the problem, we propose a technique called negative sample selection, which selects reliable negative training samples using formal concept analysis (FCA) of a given bipartite network in advance of the preceding MF process. We conduct experiments on two hypothetical application scenarios to prove that our joint method outperforms the raw MF-based link prediction method as well as all other previously-proposed unsupervised link prediction methods.

Effect of Rj genotype and cultivation temperature on the community structure of soybean-nodulating bradyrhizobia.

The nodulation tendency and community structure of indigenous bradyrhizobia on Rj genotype soybean cultivars at cultivation temperatures of 33/28°C, 28/23°C, and 23/18°C for 16/8 h (day/night degrees, hours) were investigated using 780 bradyrhizobial DNA samples from an Andosol with 13 soybean cultivars of four Rj genotypes (non-Rj, Rj(2)Rj(3), Rj(4), and Rj(2)Rj(3)Rj(4)). A dendrogram was constructed based on restriction fragment length polymorphism of the PCR products (PCR-RFLP) of the 16S-23S rRNA gene internal transcribed spacer region. Eleven Bradyrhizobium U.S. Department of Agriculture strains were used as a reference. The dendrogram indicated seven clusters based on similarities among the reference strains. The occupancy rate of the Bj123 cluster decreased with increasing cultivation temperature, whereas the occupancy rates of the Bj110 cluster, Be76 cluster, and Be94 cluster increased with increasing cultivation temperature. In particular, the Rj(2)Rj(3)Rj(4) genotype soybeans were infected with a number of Bj110 clusters, regardless of the increasing cultivation temperature, compared to other Rj genotype soybean cultivars. The ratio of beta diversity to gamma diversity (H'(ß)/H'(γ)), which represents differences in the bradyrhizobial communities by pairwise comparison among cultivation temperature sets within the same soybean cultivar, indicated that the bradyrhizobial communities tended to be different among cultivation temperatures. Multidimensional scaling analysis indicated that the infection of the Bj110 cluster and the Bj123 cluster by host soybean genotype and the cultivation temperature affected the bradyrhizobial communities. These results suggested that the Rj genotypes and cultivation temperatures affected the nodulation tendency and community structures of soybean-nodulating bradyrhizobia.