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Objective The need for tailoring ovarian cancer treatments to individual patients is increasing. This study aimed to evaluate the prognostic value of pretreatment laboratory test data for predicting the response and survival outcomes of platinum-based chemotherapy in ovarian cancer. Methods We enrolled 270 patients with ovarian cancer diagnosed at the Kyoto Medical Center (n=120; group A) and Kyoto University (n=150; group B). Data on 9 blood parameters (neutrophil to lymphocyte ratio [NLR], platelet to lymphocyte rate [PLR], C-reactive protein, lactate dehydrogenase [LDH], glucose, total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein, and triglyceride levels), cancer pathology, cancer stage, cytoreduction outcomes, serum cancer antigen 125 levels, platinum-free interval (PFI), disease-free survival (DFS), and overall survival were assessed retrospectively. Results NLR, PLR, LDH, and HDL were significantly different in advanced stage patients (P

Root development in rice (Oryza sativa L.) plays a key role in water uptake (WU) and water use efficiency (WUE) in water-saving technologies such as aerobic cultivation. Traits that contribute to root development are controlled by many complex quantitative trait loci (QTLs). Understanding the genetic mechanisms of root traits related to WUE is strategic in breeding for aerobic cultivation. Here, we mapped QTLs for root traits in double haploid lines derived from a cross between a japonica paddy rice, Koshihikari, and a japonica upland rice, Sensho. Under aerobic conditions, we detected 22 QTLs for various root and shoot traits in 2015, and 8 in 2017. WU and WUE QTLs derived from Sensho with high additive effects were detected on chromosomes 1, 6 and 10. QTLs for traits associated with WU were mapped in the same regions, forming clusters. The QTL clustering suggests inheritance as a unit and combined overall effect on plant growth, root architecture and WU, which consequently influences WUE. Evaluation of selected lines for phenotypic performance based on genotype in the QTL clusters showed that WUE of DH3, with the Sensho genotype in all cluster regions, was not significantly reduced under aerobic conditions. These results found increased WUE with increased WU by enhanced root traits, such as root length (RL), root surface area (RSA) and root volume (RV), can be obtained without incurring biomass trade-offs. Co-localization of identified QTLs for these traits may be exploited in marker-assisted breeding to develop novel high yielding varieties for aerobic cultivation.

Abstract Background Uridine diphosphate glucuronosyltransferase 1 family polypeptide A1 (UGT1A1) is a predictive biomarker for the side-effects of irinotecan chemotherapy, which reduces the volume of tumors harboring UGT1A1 polymorphisms. We aimed to determine whether UGT1A1 polymorphisms can predict progression-free survival in patients with local cervical cancer treated with irinotecan chemotherapy. Methods We retrospectively analyzed the data of 51 patients with cervical cancer treated at a single institution between 2010 and 2015. All patients were diagnosed with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IB1, IB2, IIA, or IIB squamous cell carcinoma, underwent radical hysterectomy, and received irinotecan chemotherapy as neoadjuvant and/or adjuvant treatment. All patients were examined for irinotecan side effects using UGT1A1 tests. Conditional inference tree and survival analyses were performed considering the FIGO stage, age, the UGT1A1 status, and the number of metastatic lymph nodes to determine primary factors associated with progression-free survival. Results The tree-structured survival model determined high recurrence-risk factors related to progression-free survival. The most relevant factor was ≥2 metastatic lymph nodes (p = 0.004). The second most relevant factor was UGT1A1 genotype (p = 0.024). Among patients with ≤1 metastatic lymph node, those with UGT1A1 polymorphisms benefited from irinotecan chemotherapy and demonstrated significantly longer progression-free survival (p = 0.020) than those with wild-type UGT1A1. Conclusions Irinotecan chemotherapy might be beneficial in patients with cervical cancer, UGT1A1 polymorphisms, and ≤ 1 metastatic lymph nodes.

Signal transmission and regulation of G-protein-coupled receptors (GPCRs) by ligands occurs via modulation of complex conformational equilibria. Here authors quantify these equilibria and their dynamics in the β1-adrenergic receptor in its apo form and seven ligand complexes using NMR.

Abstract Several studies have demonstrated increased pericardial effusion during anti‐PD‐1 immunotherapy, and treatment in patients who have developed pericardial tamponade is controversial. In this study, we describe a 63‐year‐old woman with stage IVA lung adenocarcinoma given pembrolizumab as a first‐line therapy. After four cycles of pembrolizumab treatment, the patient suddenly developed a pericardial tamponade. Although pericardial effusion was increased, her tumor lesions were reduced. After an emergency pericardiocentesis, she continued the pembrolizumab therapy without recurrent pericardial effusions for three months until the primary tumor and lymph node metastasis progressed. Nine months after the pericardiocentesis, the patient died of progressive lung cancer, but pericardial effusion did not recur throughout the treatment course. This case study suggests that pembrolizumab therapy can be continued with a strict follow‐up in some patients with pembrolizumab‐induced pericardial tamponade. Key points • Significant findings of the study Our patient developed pericardial tamponade during pembrolizumab treatment but continued pembrolizumab treatment after emergency pericardiocentesis without recurrent pericardial effusions. • What this study adds Pembrolizumab treatments may be resumed with a strict follow‐up in some patients with treatment‐related pericardial tamponade.

Abstract Background Biliary bleeding is a condition reported by Sandblom as hemobilia. The most common cause of hemobilia is iatrogenicity. But it has also been reported as a rare complication after laparoscopic cholecystectomy (LC). Case presentation A man in his 60s underwent a LC. He was taking a direct Xa inhibitor for paroxysmal atrial fibrillation (pAf) and had a history of thrombectomy. There was variation in the bifurcation of the hepatic artery and cystic artery. The right hepatic artery branches from the common hepatic artery by itself, and the cystic artery is double. He complained of right upper quadrant pain, nausea, and vomiting on the third postoperative day (3POD). Non-contrast computed tomography (CT) showed that a high absorption area was found to fill the common bile duct. Contrast CT showed no pseudoaneurysm formation. Ultimately, he was diagnosed with postoperative hemobilia. Angiographic examination selective for the cystic artery branching from the middle hepatic artery revealed leakage of the contrast agent and a micro-pseudoaneurysm. Conclusions We encountered a case of hemobilia after LC. In this case, it was presumed that in addition to the chronic inflammatory changes of the gallbladder wall, extraordinary bifurcation of the hepatic artery and the cystic arteries and easy bleeding due to resumption of a direct Xa inhibitor synergistically caused a micro-pseudoaneurysm and postoperative hemobilia. It was difficult to identify the cause of hemobilia by contrast CT alone. Angiographic examination was useful for identifying and treating the causative artery and needs to perform aggressively.

In the fifth-generation of mobile communications, network slicing is used to provide an optimal network for various services as a slice. In this paper, we propose a radio access network (RAN) slicing method that flexibly allocates RAN resources using deep reinforcement learning (DRL). In RANs, the number of slices controlled by a base station fluctuates in terms of user ingress and egress from the base station coverage area and service switching on the respective sets of user equipment. Therefore, when resource allocation depends on the number of slices, resources cannot be allocated when the number of slices changes. We consider a method that makes optimal-resource allocation independent of the number of slices. Resource allocation is optimized using DRL, which learns the best action for a state through trial and error. To achieve independence from the number of slices, we show a design for a model that manages resources on a one-slice-by-one-agent basis using Ape-X, which is a DRL method. In Ape-X, because agents can be employed in parallel, models that learn various environments can be generated through trial and error of multiple environments. In addition, we design a model that satisfies the slicing requirements without over-allocating resources. Based on this design, it is possible to optimally allocate resources independently of the number of slices by changing the number of agents. In the evaluation, we test multiple scenarios and show that the mean satisfaction of the slice requirements is approximately 97%.

Several cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection transmitted from human owners to their dogs have recently been reported. The first ever case of SARS-CoV-2 transmission from a human owner to a domestic cat was confirmed on March 27, 2020. A tiger from a zoo in New York, USA, was also reportedly infected with SARS-CoV-2. It is believed that SARS-CoV-2 was transmitted to tigers from their caretakers, who were previously infected with this virus. On May 25, 2020, the Dutch Minister of Agriculture, Nature and Food Quality reported that two employees were infected with SARS-CoV-2 transmitted from minks. These reports have influenced us to perform a comparative analysis among angiotensin-converting enzyme 2 (ACE2) homologous proteins for verifying the conservation of specific protein regions. One of the most conserved peptides is represented by the peptide “353-KGDFR-357 (H. sapiens ACE2 residue numbering), which is located on the surface of the ACE2 molecule and participates in the binding of SARS-CoV-2 spike receptor binding domain (RBD). Multiple sequence alignments of the ACE2 proteins by ClustalW, whereas the three-dimensional structure of its binding region for the spike glycoprotein of SARS-CoV-2 was assessed by means of Spanner, a structural homology modeling pipeline method. In addition, evolutionary phylogenetic tree analysis by ETE3 was used. ACE2 works as a receptor for the SARS-CoV-2 spike glycoprotein between humans, dogs, cats, tigers, minks, and other animals, except for snakes. The three-dimensional structure of the KGDFR hosting protein region involved in direct interactions with SARS-CoV-2 spike RBD of the mink ACE2 appears to form a loop structurally related to the human ACE2 corresponding protein loop, despite of the reduced available protein length (401 residues of the mink ACE2 available sequence vs 805 residues of the human ACE2). The multiple sequence alignments of the ACE2 proteins shows high homology and complete conservation of the five amino acid residues: 353-KGDFR-357 with humans, dogs, cats, tigers, minks, and other animals, except for snakes. Where the information revealed from our examinations can support precision vaccine design and the discovery of antiviral therapeutics, which will accelerate the development of medical countermeasures, the World Health Organization recently reported on the possible risks of reciprocal infections regarding SARS-CoV-2 transmission from animals to humans.

Psychological stress is associated with various oral diseases such as aphthous stomatitis, oral lichen planus, taste disturbances and glossodynia. However, the underlying mechanism is still unknown. The aim of this study was to determine the effect of psychological stress on salivary proteins and the oral microbiota in a rat model of chronic restraint stress. Six-week-old Sprague Dawley rats were subjected to restraint stress for four hours daily for 1 month. The behavior, weights of the adrenal glands, and serum corticosterone levels were evaluated as stress markers. Proteomic analysis of the saliva was performed using two-dimensional gel electrophoresis followed by mass spectrometry and Western blotting. Analysis of the oral microbiota was performed via 16S rRNA next-generation sequencing. The low mean body weights, lower number of entries and time spent in the open arm of elevated plus maze, high adrenal gland/body weight ratios, and high serum corticosterone levels confirmed the high levels of stress in the stress group of rats compared to the controls. Thirty-three protein spots were found to be significantly altered between the two groups. After silver staining, seven visible spots were subjected for mass spectrometry, and the expression levels of the two most significantly altered proteins, BPI fold containing family A member 2 and von Ebner's gland protein, were confirmed by Western blotting. 16S rRNA sequencing analysis revealed a significant reduction in alpha diversity in the stress group compared to the controls. The abundances of oral bacteria, such as Facklamia and Corynebacterium, were significantly altered between the two groups. Additionally, analysis with PICRUSt2 software predicted 37 different functional pathways to be altered between the groups. In conclusion, the present study identified altered salivary proteins and oral microbiota due to psychological stress. These findings might aid in understanding the pathogenesis of stress-related oral diseases.

For long-term treatment of hepatitis B virus (HBV) infection, switching from tenofovir-disoproxil-fumarate (TDF) to tenofovir-alafenamide (TAF) may prevent renal dysfunction and bone loss. However, the precise effects of this switch on the blood lipid profile remain to be clarified. This is an important issue as TDF is known to have effects on both low- and high-density lipids. Therefore, our retrospective multi-center study aimed to evaluate the effects of switching from TDF to TAF on the lipid profile of patients with HBV infection. Samples were obtained prior to the switch from TDF to TAF and at 6-12 months after TAF initiation. In some cases, additional samples obtained pre- and post-TDF administration were available for analysis. Serum cholesterol levels, including oxidized-low-density lipoprotein (LDL) and non-high-density lipoprotein-cholesterol (HDL-c), and the rate of dyslipidemia, according to the NCEP-ATP III lipid risk classification, were analyzed. The data from 69 patients were analyzed, including 33 patients with pre- and post-TDF-initiation serum samples. Total cholesterol (T-chol), HDL-c, LDL-c, non-HDL-c, and oxidized LDL levels increased significantly after switching to TAF. With regard to sequential changes pre- to post-TAF, TDF was associated with significantly lower serum T-chol, HDL-c, and oxidized LDL-c levels, with T-chol, HDL-c, LDL-c, and oxidized LDL-c levels increasing significantly after the switch. The switch from TDF to TAF was also associated with an increase in the rate of dyslipidemia, from 33% to 39%, with an increase in the rate of severe dyslipidemia of 1.4% and 5.8%, based on T-chol and LDL-c levels. Of note, no cases of severe dyslipidemia were detected pre-TAF treatment. As oxidized LDL-c and non-HDL-c are strongly associated with atherosclerosis development, careful monitoring of lipid is needed after switching from TDF to TAF in this clinical population.

In Ethiopia, more prevalent drought happenings have been documented in the past century. The problem has gradually expanded from the north to the rest parts with deepened intensity. The study aimed to examine the magnitudes of spatiotemporal patterns of drought at the Bilate watershed from 1981 to 2016. Monthly rainfall and temperature data were used for the analysis. The Standardized Evapotranspiration Indexes (SPEI) at SPEI-03 and SPEI-12 timescales were applied to evaluate the drought patterns. Among different drought indices, the SPEI is the most valuable and preferred Index for drought studies. The SPEI method considers the role of temperature than other indices to compare drought in time and space. The Mann–Kendall test was used for trend analysis. Accordingly, the result revealed that 1988–2016 were years of continuous drought events in both timescales with (SPEI = −2.5 to −1.2) drought value. Drought severity and frequency were highly detected at Wulberag areas (SPEI: −2.5). Durame, Angacha, and Alaba experienced increasing drought trends (Z = −1.96−1.6) and Welayita Sodo is Z = −0.07−0.03. Bilate-Tena and Hossana area of the watershed were less affected by drought than other areas. Spatially, the drought occurrences were observed in all areas of the watershed with varying magnitude. In the SPEI-12 timescale, more frequent drought occurrences were observed than SPEI-03. It was found that severe drought was observed in 1987, 1993/94, 2000–2005, and 2010. Moreover, the watershed experienced an Aridity Index (AI) of 0.43 (43%) and was subjected to potential high evapotranspiration (PET). The highest PET was observed at Bilate-Tena, Angacha, Hosanna, Wulberag, Alaba, Welayita Sodo, and Durame (151.6, 119.6, 119.3, 140.8, 142, 127.5, and 125.7 mm/year, respectively. Hence, the finding of this study could initiate a further inquiry on drought risk management, early warning responses, and local scale planning.

resumo Elaborado com base na análise de dados oficiais, documentos internacionais, textos legislativos e extensa revisão bibliográfica, este artigo apresenta algumas reflexões sobre temas relevantes à implementação, pelas cidades brasileiras, dos Objetivos do Desenvolvimento Sustentável, fixados pela Agenda 2030 para o Desenvolvimento Sustentável da Organização das Nações Unidas, apontando os instrumentos legais existentes no âmbito da Política Nacional do Meio Ambiente, Política de Gestão de Recursos Hídricos, Estatuto da Cidade e Política Nacional de Proteção e Defesa Civil, com ênfase às ações e estratégias urbanas de mitigação, adaptação e resiliência às mudanças climáticas, no intuito de contribuir, na universidade, para a orientação de pesquisas científicas inter e transdisciplinares, articuladas com a formulação, implementação e avaliação de políticas públicas e voltadas a prover soluções para o enfrentamento dos complexos desafios de gestão e planejamento enfrentados pelas cidades contemporâneas.