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Purpose Information on milk transferability of drugs is important for patients who wish to breastfeed. The purpose of this study is to develop a prediction model for milk-to-plasma drug concentration ratio based on area under the curve (M/PAUC). The quantitative structure–activity/property relationship (QSAR/QSPR) approach was used to predict compounds involved in active transport during milk transfer. Methods We collected M/P ratio data from literature, which were curated and divided into M/PAUC ≥ 1 and M/PAUC Results M/P ratios of 403 compounds were collected, M/PAUC data were obtained for 173 compounds, while 230 compounds only had M/Pnon-AUC values reported. The models were constructed using 129 of the 173 compounds, excluding colostrum data. The sensitivity of the ANN model was 0.969 for the training set and 0.833 for the test set, while the sensitivity of the SVM model was 0.971 for the training set and 0.667 for the test set. The contribution of the charge-based descriptor was high in both models. Conclusions We built a M/PAUC prediction model using QSAR/QSPR. These predictive models can play an auxiliary role in evaluating the milk transferability of drugs.

To investigate short-term treatment outcomes of intravitreal brolucizumab (IVBr) for treatment-naïve neovascular age-related macular degeneration (AMD) in a Japanese multicenter study.Retrospective case control study METHODS: The subjects were 58 eyes of 57 patients with neovascular AMD (43 men and 14 women, mean age 74.6 years) of whom 43 eyes of 42 patients completed initial loading of 3 monthly IVBr injections and were followed for more than 3 months. Best-corrected visual acuity (BCVA) changes, anatomical outcomes, and complications were investigated.Of the 43 eyes that completed loading doses, the AMD subtype was type 1 and type 2 macular neovascularization (MNV) in 51%, polypoidal choroidal vasculopathy (PCV) in 42%, and type 3 MNV in 7%. At 3 months after initiating treatment, BCVA significantly improved (P = 0.002) and central retinal thickness significantly decreased (P 0.0001). At 3 months, complete retinal and subretinal fluid resolution was achieved in 91% of all eyes and complete regression of polypoidal lesions was achieved in 82% of PCV eyes. Iritis occurred in 8 eyes of 8 patients (14%), but resolved using topical or subtenon corticosteroid injection without visual loss in all cases.IVBr for treatment-naïve neovascular AMD was effective in the short-term, achieving significantly improved BCVA, good retinal fluid resolution, and a high rate of polypoidal lesion regression. However, iritis was noted in 14% of patients which may limit use of this drug.

Introduction The occurrence of massive haemorrhages in various emergency situations increases the need for blood transfusions and increases the risk of mortality. Fibrinogen concentrate (FC) use may increase plasma fibrinogen levels more rapidly than fresh-frozen product or cryoprecipitate use. Previous several systematic reviews and meta-analyses have not effectively demonstrated FC efficacy in significantly improving the risk of mortality and reducing transfusion requirements. In this study, we investigated the use of FC for haemorrhages in emergency situations. Methods and analysis In this systematic review and meta-analysis, we included controlled trials, but excluded randomized controlled trials (RCTs) in elective surgeries. The study population consisted of patients with haemorrhages in emergency situations, and the intervention was emergency supplementation of FC. The control group was administered with ordinal transfusion or placebo. The primary and secondary outcomes were in-hospital mortality and the amount of transfusion and thrombotic events, respectively. The electronic databases searched included MEDLINE (PubMed), Web of Science, and the Cochrane Central Register of Controlled Trials. Results Nine RCTs in the qualitative synthesis with a total of 701 patients were included. Results showed a slight increase in in-hospital mortality with FC treatment (RR 1.24, 95% CI 0.64–2.39, p = 0.52) with very low certainty of the evidence. There was no reduction in the use of red blood cells (RBC) transfusion in the first 24 h after admission with FC treatment (mean difference [MD] 0.0 Unit in the FC group, 95% CI − 0.99–0.98, p = 0.99) with very low certainty of the evidence. However, the use of fresh-frozen plasma (FFP) transfusion significantly increased in the first 24 h after admission with FC treatment (MD 2.61 Unit higher in the FC group, 95% CI 0.07–5.16, p = 0.04). The occurrence of thrombotic events did not significantly differ with FC treatment. Conclusions The present study indicates that the use of FC may result in a slight increase in in-hospital mortality. While FC did not appear to reduce the use of RBC transfusion, it likely increased the use of FFP transfusion and may result in a large increase in platelet concentrate transfusion. However, the results should be interpreted cautiously due to the unbalanced severity in the patient population, high heterogeneity, and risk of bias.

An 80-year-old man presented to our emergency department complaining of a mass on the right side of his chest and pain in the right flank of his back. A chest computed tomography (CT) scan showed a relatively heterogenous oval-shaped tumor measuring 7.5 × 6.0 cm eroded to the 8th rib, with slightly dense fluid accumulation inside and calcification of the tumor wall. A 1-month follow-up CT scan showed spontaneous shrinkage of the tumor. The tumor was completely excised from the thoracic wall and the wall was reconstructed with a polytetrafluoroethylene mesh. Pathological examination showed coagulation necrosis in the chest wall tumor, but immunohistochemical staining revealed murine double minute 2- and Cyclin-dependent kinase 4-positive cells with irregular nuclear size and bizarre morphology. Therefore, dedifferentiated liposarcoma (DDLPS) was the final pathological diagnosis. Remarkable infiltration of CD8+ lymphocytes into the tumor was observed, along with a 90% positive ratio for programmed cell death-ligand 1. The patient has been followed-up for 1 year without any recurrence, despite not receiving any additional treatment. Liposarcoma is one of the most common types of soft tissue sarcomas; however, spontaneous regression of primary DDLPS arising from the chest wall is extremely rare. Herein, we report a case of DDLPS primary to the chest wall with spontaneous regression, probably due to a spontaneously induced T cell response.

Background Cellular angiofibroma (CA) is a rare, benign mesenchymal tumor first described by Nucci et al. (Am J Surg Pathol 21:636–644, 1997. 10.1097/00000478-199706000-00002). It affects both men and women, although it is more common in middle-aged women. CA is well circumscribed and usually observed on the body surface, primarily in distal genital regions. Aggressive angiomyxoma and angiomyofibroblastoma are clinically and histologically similar; therefore, it may be necessary to distinguish between CA and these similar tumors. We present a rare case of CA, with atypical features, in the retroperitoneal space during pregnancy. Case presentation The presence of a 130 mm tumor was detected in a 19-year-old woman. The tumor, located in the retroperitoneal space, was found during first pregnancy examination. At 16 weeks of gestation, the woman developed nausea and fever, and it was diagnosed with acute pyelonephritis. After a few days, the amniotic membranes prematurely ruptured, leading to a miscarriage. The woman underwent a tumor resection, after miscarriage. This case presented with atypical features of CA. This included the young age of the patient, and presence of a tumor in the retroperitoneal space. Conclusion In this case, the diagnosis of CA was difficult due to the rarity of the disease and its atypical clinical features. From this experience, we recommend that the discussion on the efficacy of surgical treatment and pregnancy outcomes should be done based on individual case, and not generalized.

Some studies have asked participants about attentional state on a scale from on-task to off-task, which set the middle option as attention focused on both, including the possibility of the coexistence of thoughts. In addition, studies using multidimensional probes explicitly assumed coexistence within spontaneous thoughts and task-focus dimensions. Although several studies have assumed the coexistence of some thought dimensions, none has explored whether these are different types of thoughts (task-focus, mind-wandering, task-related, external stimuli-related). To examine whether this coexistence of thought types occurred, we used thought probes to determine the degree of immersion in each. The participants responded to probes presented at random during a sustained attention task. The results revealed a mixture of thought types in many self-reports. In addition, the state of attentional allocation behind self-reports was estimated using the hidden Markov model. We observed the following attentional states: task-focused, task-unrelated, task-related, external stimuli-focused, and task-focused—but also focused on other thoughts. These results suggest that individuals can simultaneously allocate attention to thought types and discriminate between reporting. In some cases, probe options should also be considered for this coexistence. We also examined the relationship between self-reports and behavioral indexes, and discussed the necessity of separately measuring the degree of immersion for each thought type.

Close observation of the local transmission of influenza A(H1N1) viruses enabled an estimate of the length of time the virus was transmitted without a mutation. Of 4,448 isolates from 11 consecutive years, 237 isolates could be categorized into 57 strain groups with identical hemagglutinin genes, which were monitored for the entire duration of an epidemic season. In addition, 35 isolates with identical sequences were identified at the study site and in other countries within 147 days. Consequently, it can be postulated that once an influenza virus enters a temperate region, the strain rarely mutates before the end of the season.

An inverse correlation between body mass index and mortality in patients with peripheral artery disease (PAD) has been reported. However, little information is available regarding the impact of body composition on the clinical outcomes in patients with PAD. This study evaluated the relationships between the lean body mass index (LBMI), body fat % (BF%), and mortality and major amputation rate in patients with PAD. We evaluated 320 patients with PAD after endovascular treatment (EVT) enrolled from August 2015 to July 2016 and divided them into low and high LBMI and BF% groups based on their median values (17.47 kg/m2and 22.07%, respectively). We assessed 3-year mortality and major amputation for the following patient groups: Low LBMI/Low BF%, Low LBMI/High BF%, High LBMI/Low BF%, and High LBMI/High BF%. During the median 3.1-year follow-up period, 70 (21.9%) patients died and 9 (2.9%) patients experienced major amputation. The survival rate was lower in the Low LBMI than in the High LBMI group, and was not significantly different between the Low and High BF% groups. Survival rates were lowest in the Low LBMI/Low BF% group (57.5%) and highest in the High LBMI/High BF% group (94.4%). There were no significant differences in major amputation rate between the Low LBMI and High LBMI groups, and between the Low BF% and High BF% groups. The Low LBMI and Low BF% groups were associated with an increased risk of mortality after adjustment for age, sex, frailty and conventional risk factors [hazard ratio (HR): 4.02; 95% confidence interval (CI) 2.10–7.70;p p = 0.005, respectively], for age, sex, hemodialysis, and prior cerebral cardiovascular disease (HR: 3.63; 95% CI 1.93–6.82;p p = 0.009, respectively) and for age, sex, and laboratory date (HR: 3.97; 95% CI 1.88–8.37;p p = 0.026, respectively). In conclusion, Low LBMI and Low BF% were associated with poor prognosis in patients undergoing EVT for PAD, and mortality was the lowest in the High LBMI/High BF% group compared with other body composition groups.

Enterohemorrhagic Escherichia coli are a dangerous bacterium known to be harmful to the human body, with some infections even resulting in death. Given this danger, food factories are required to perform a quick bacterial test to confirm the absence of this pathogen prior to shipping. We have developed a novel molecular imprinting polymer (MIP) particle that has encapsulated gold nanoparticles (AuNPs) and which can function as both a receptor and an optical signal transmitter in biological systems. This MIP particle is artificially synthesized and can be engineered to specifically recognize and capture antigens on the bacterial cell membrane. In addition, MIP particles containing AuNPs generate strong scattered light signals, and binding of the MIP particles improves the optical intensity of the target bacterial cells. This enables clear visualization under a dark-field microscope and quantification of the target bacteria using the scattering light intensity. Here we describe the successful quantification of Escherichia coli O157 cells in real meat samples using this technology in conjunction with a simple labelling step.

Background Aortopulmonary mediastinal paragangliomas are rare. Complete resection of the tumor is desirable regardless of tumor size in view of the risk of sudden death induced by adjacent organ compression and poor prognosis after partial resection or untreated observation. Due to the hypervascularity of the tumor, the risk of intraoperative bleeding is significant, and cardiopulmonary bypass is often required for complete resection. Case presentation The patient was diagnosed as having bilateral carotid body tumors and supposedly an aortic body tumor at the age of 43 and eventually underwent resections of bilateral carotid body tumors at the age of 52. The pathology of the carotid body tumors was compatible with paraganglioma on both sides. A familial succinate dehydrogenase subunit D mutation was subsequently identified. Five years later, a contrast-enhanced computed tomography scan showed an enlarged tumor of 45 mm in size in the aortopulmonary mediastinum. Based on the previously known genetic mutation, the tumor was thought to be a paraganglioma. After confirming with an endocrinologist that the aortic body tumor was non-functional, radiologists performed preoperative embolization of the feeding vessels. Subsequently, a surgical team consisting of thoracic and cardiovascular surgeons resected the aortic body tumor using a video-assisted small left thoracotomy approach combined with a median sternotomy approach. The procedure was completed without cardiopulmonary bypass or blood transfusion. The patient was discharged home on postoperative day 9 uneventfully. Conclusions After conduction of preceding interventional embolization of multiple feeding vessels, we employed a video-assisted thoracoscopic surgical approach to dissect the aspects of the tumor adjacent to the esophagus, descending thoracic aorta, and left pulmonary artery, followed by a median sternotomy approach to dissect the other aspects of the tumor adjacent to the ascending aorta, aortic arch, right pulmonary artery, and trachea. There have been no reports on scheduled preoperative embolization of feeding vessels to an aortopulmonary mediastinal paraganglioma. Multidisciplinary approach was effective for complete resection of this challenging rare mediastinal tumor.

Discharge plasma irradiates seeds with reactive oxygen and nitrogen species (RONS). However, RONS introduced in seeds by plasma irradiation have not been successfully detected thus far. This study provides experimental evidence that nitrate ion NO3− is introduced in lettuce seeds as RONS upon irradiation with atmospheric-pressure air dielectric barrier discharge plasma. Plasma irradiation for 5 min promotes seed germination. The components of the plasma-irradiated seeds were examined using electrospray ionization quantum mass spectrometry (ESI QMS), which revealed that the plasma irradiation introduced an ion with a mass of 62 m/z in detectable amounts. This ion was identified as NO3− by liquid chromatography (LC), multiple wavelength detector (MWD), and LC-ESI QMS. A one-dimensional simulation at electron temperature Te = 1 eV, electron density Ne = 1013/m3, and gas temperature Tg = 300 K indicated the introduction of NO3−, involving nitric oxide NO. NO3− is one of the most important ions that trigger signal transduction for germination when introduced in seeds. The scanning electron microscopy (SEM) images revealed that there was no change on the surface of the seeds after plasma irradiation. Plasma irradiation is an effective method of introducing NO3− in seeds in a dry process without causing damage.

The correlation of viral growth capability (n = 156) with the viral load in nasopharyngeal swabs (n = 76) was assessed. Epidemic influenza A/H1N1, A/H3N2, and B viruses showed a wide range of growth capability (104–1011 copies/mL) in Madin-Darby canine kidney cells. The growth was correlated with the nasopharyngeal viral load (r = 0.53). Six selected strains showed growth-dependent cell death (r = 0.96) in a growth kinetics assay. Epidemic influenza viruses exhibit a wide range of growth capability. Growth capability should be considered one of the key factors in disease prognosis.

Understanding the population structure of Fasciola flukes in domestic and wild animals is important for determining the extent of cross-infection between them. Although the parthenogenetic Fasciola flukes in Japan have been shown to comprise five genetic types based on the ribosomal internal transcribed spacer 1 (ITS1) and mitochondrial NADH dehydrogenase subunit 1 (nad1) regions, these genetic regions are not suitable for analyzing their population structure. In the present study, the genetic diversity and population structure of the parthenogenetic Fasciola flukes in Japan were studied using microsatellite DNA, ITS1, and nad1 regions. A total of 144 parthenogenetic Fasciola flukes, obtained from cattle and sika deer in 16 localities, were individually analyzed using PCR-RFLP for ITS1, PCR-direct sequence analysis for nad1, and post-labeling PCR and capillary electrophoresis for microsatellite DNA regions. The flukes showed higher genetic diversity in the microsatellite DNA regions than ITS1 and nad1. The population structures of parthenogenetic Fasciola flukes were unclear, however, it was suggested that the flukes are more diverse populations. We hypothesized that their distribution throughout Japan is closely related to livestock movement dependent on human activity. Moreover, it is considered that cross-infection of the flukes between cattle and sika deer possibly has occurred in the past.

Monitoring of the adequacy of myocardial protection with cardioplegia is nearly non-existent in clinical cardiac surgical practice and instead relies on well-defined protocols for delivery of cardioplegia often resulting in inadequate protection. We hypothesized that Near Infrared Spectroscopy technology could be useful in the monitoring of the myocardial oxygen state by attaching the monitors to the epicardium in a porcine model of cardiac surgery. The experiments were conducted with 3 different protocols of 2 pigs each for a total of 6 pigs. The objective was to induce episodic, oxygen supply-demand mismatch. Methods for decreased supply included decreasing coronary blood flow, coronary blood hypoxemia, coronary occlusion, hypovolemia, and hypotension. Methods for increase demand included rapid ventricular pacing and the administration of isoproterenol. Changes in myocardial tissue oximetry were measured and this measurement was then correlated with blood hemoglobin saturations of oxygen from coronary sinus blood samples. We found that decreases in myocardial oxygen supply or increases in demand due to any of the various experimental conditions led to decreases in both myocardial tissue oximetry and hemoglobin oxygen saturation of coronary sinus blood with recovery when the conditions were returned to baseline. Correlation between myocardial tissue oximetry and hemoglobin oxygen saturation of coronary sinus blood was moderate to strong under all tested conditions. This may have translational applications as a monitor of adequacy of myocardial protection and the detection of coronary occlusion.

Nitrogen (N) resorption from senescing leaves enables plants to reuse N, thereby making them less dependent on current N uptake from the environment. Therefore, N resorption is important for survival and fitness, particularly for plants growing under low N supply. We studied N resorption from senescing leaves of 25 legumes and 25 nonlegumes in a temperate region of Japan to test the hypothesis that high N resorption has not evolved in legumes that fix atmospheric N2. The extent of N resorption was quantified by N resorption proficiency that is measured as the level to which leaf N concentration was reduced during senescence, i.e., the lower the senesced leaf N concentration, the lower the N loss through leaf fall and higher the N resorption proficiency. In support of the hypothesis, senesced leaf N concentration was higher in legumes than in nonlegumes, but there was considerable overlap between the groups. The higher senesced leaf N concentration of legumes was associated with a lower proportion of leaf N resorbed during senescence, particularly in species with higher leaf N concentrations. According to a hierarchical partitioning analysis, there was a large contribution of species to the total variance in the senesced leaf N concentration as opposed to a minor contribution of functional group (legume/nonlegume). This study reveals that legumes are not proficient at resorbing N from senescing leaves but that N2-fixation might not be the single most important determinant of N resorption.

A long-standing crucial question with atomic nuclei is whether or not α clustering occurs there. An α particle (helium-4 nucleus) comprises two protons and two neutrons, and may be the building block of some nuclei. This is a very beautiful and fascinating idea, and is indeed plausible because the α particle is particularly stable with a large binding energy. However, direct experimental evidence has never been provided. Here, we show whether and how α(-like) objects emerge in atomic nuclei, by means of state-of-the-art quantum many-body simulations formulated from first principles, utilizing supercomputers including K/Fugaku. The obtained physical quantities exhibit agreement with experimental data. The appearance and variation of the α clustering are shown by utilizing density profiles for the nuclei beryllium-8, -10 and carbon-12. With additional insight by statistical learning, an unexpected crossover picture is presented for the Hoyle state, a critical gateway to the birth of life.