The role of balanced time perspective mediating the relationship between mindfulness as a trait and life satisfaction in Catalan University students.
The objective of the present study was to replicate previous studies by examining the potential connections between mindfulness as a trait, life satisfaction and time perspectives (TP) and to analyze if balanced time perspective (BTP) could act as a possible mediator between mindfulness and life satisfaction in students from the University of Girona (Catalonia, Spain). Data was collected from 341 Catalan university students aged 18-52 (77.1% women; mean age = 23.62) who completed Zimbardo Time Perspective Inventory (ZTPI), the Mindfulness Awareness Scale (MAAS) and the Satisfaction with Life Scale (SWLS) to assess their Temporal Perspective, Mindfulness as a trait and Life Satisfaction respectively. Balanced time perspective (BTP) was calculated using the deviation index of BTP (DBTP). Results showed significant relationships between the various temporal dimensions, life satisfaction, and mindfulness as a trait, being the most significant associations with balanced temporal perspective. On the other hand, results also suggested that BTP may act as a mediator between mindfulness as a psychological trait and life satisfaction, confirming previous studies conducted in different countries. In conclusion, findings could highlight the importance of regulating one's attention in order to balance time perspectives, which in turn would translate into improved life satisfaction. The online version contains supplementary material available at 10.1007/s12144-022-03795-4.


Multiplexed imaging of tumor immune microenvironmental markers in locally advanced or metastatic non-small-cell lung cancer characterizes the features of response to PD-1 blockade plus chemotherapy.
Although programmed cell death 1 (PD-1) blockade plus chemotherapy can significantly prolong the progression-free survival (PFS) and overall survival (OS) in first-line settings in patients with driver-negative advanced non-small-cell lung cancer (NSCLC), the predictive biomarkers remain undetermined. Here, we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus chemotherapy. Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy alone. Tumor immune microenvironmental markers, including PD-1 ligand (PD-L1), CD8, CD68, CD4 and forkhead box P3, were assessed using multiplex immunofluorescence (mIF) assays. Kaplan-Meier curves were used to determine treatment outcome differences according to their expression status. Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations. Responders had significantly higher CD8/PD-L1 (P = 0.015) or CD68/PD-L1 co-expression levels (P = 0.021) than non-responders in the camrelizumab plus chemotherapy group, while no difference was observed in the chemotherapy group. Patients with high CD8/PD-L1 or CD68/PD-L1 co-expression level was associated with significantly longer PFS (P = 0.002, P = 0.024; respectively) and OS (P = 0.006, P = 0.026; respectively) than those with low co-expression in camrelizumab plus chemotherapy group. When comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD-L1 co-expression stratification, significantly better PFS (P = 0.003) and OS (P = 0.032) were observed in high co-expression subgroups. The predictive value of CD8/PD-L1 and CD68/PD-L1 co-expression remained statistically significant for PFS and OS when adjusting clinicopathological features. Although the prevalence of TP53 or KRAS mutations was similar between patients with and without CD8/PD-L1 or CD68/PD-L1 co-expression, the positive groups had a significantly higher proportion of TP53/KRAS co-mutations than the negative groups (both 13.0% vs. 0.0%, P = 0.023). Notably, enriched PI3K (P = 0.012) and cell cycle pathway (P = 0.021) were found in the CD8/PD-L1 co-expression group. Tumor immune microenvironmental marker expression, especially CD8/PD-L1 or CD68/PD-L1 co-expression, was associated with the efficacy of PD-1 blockade plus chemotherapy as first-line treatment in patients with advanced NSCLC.


Factors associated with reduced fertility and implantation rates in females mated to acrylamide-treated rats.
A series of studies was conducted to examine the role of copulatory dysfunction, spermatotoxicity, and/or impaired fertilization in the reduced rates of fertility and implantation observed in females mated to acrylamide-treated male rats. In initial experiments, males were gavaged with 0, 5, 15, 30, 45, or 60 mg/kg acrylamide (ACR) for 5 days and then mated serially to naive females. ACR treatment reduced fertility and increased pre- and post-implantation loss, primarily over the first 3 weeks post-treatment. The effects at Week 1 appeared to result from an interference in sperm transport as demonstrated by the absence of sperm in the uteri of females following a single ejaculation by ACR-treated male rats. The effect however was transient, with recovery of fertility in all but the 60 mg/kg group by Week 2. Attempts to explain the reduced rate of implantation concentrated on characterizing changes in measures of ejaculated sperm count and various motility parameters and evaluating sperm fertilizing ability. Males were again dosed acutely with ACR (p.o.). ACR produced statistically significant, but modest, alterations in sperm motility at Week 3. More prominent was the marked decrease in the number of fertilized ova recovered from females mated to ACR-treated males at Week 3. These data suggest that events critical to the fertilizing ability of the sperm appear to play a major role in the reduced reproductive competence associated with ACR treatment in male rats.


Comparison for quantification of eight components in Alpinia officinarum Hance by using high-performance liquid chromatography coupled with diode array detector and charged aerosol detector with individual and substitute reference compound.
An efficient HPLC-DAD-CAD method was developed and compared for simultaneous quantification of four flavonoids and four diarylheptanoids in Alpinia officinarum Hance (A. officinarum) using individual and substitute reference compound. All calibration curves for investigated analytes showed good linear regression (R2> 0.9991). The LODs of investigated compounds for DAD and CAD were 0.15-7.92 ng (0.03-1.58 μg/mL) and 2.91-3.95 ng (0.58-0.79 μg/mL), respectively, whereas the LOQs were 0.52-26.39 ng (0.10-5.28 μg/mL) for DAD, and 9.70-13.18 ng (1.94-2.64 μg/mL) for CAD. Recoveries of all analytes, which ranged from 96.58% to 100.06% for DAD, and from 96.29% to 99.61% for CAD, were acceptable. According to the quantitative results, the eight compounds in A. officinarum can be accurately quantified with individual calibration curves by two detectors. In addition, to overcome the bottleneck of shortage of reference standards, diphenylheptane A and galangin, respectively, were selected for direct or calibrated quantitative determination of other diarylheptanoids and flavonoids in A. officinarum. The results showed the contents of eight components in A. officinarum determined by these methods were similar, which suggested that substitute reference compound was suitable for quantification of its analogues.


The impact of residency training level on early postoperative desaturation: A retrospective multicenter cohort study.
We studied the primary hypothesis that the training level of anesthesiology residents (first clinical anesthesia year, CA1 vs CA2/3 residents) is associated with early postoperative desaturation (oxygen saturation < 90%). We also analyzed the change in the rate (trajectory) of desaturation during the resident's development from CA1 to CA2/3 resident, and its effects on postoperative respiratory complications. Retrospective hospital registry study. Two university-affiliated hospitals networks (MA and NY, USA). 140,818 adults undergoing non-cardiac surgery under general anesthesia and extubation in the operating room by residents (n = 378) between 2005 and 2021. Multivariate logistic and quantile regression were used in the analyses. The secondary outcome was major respiratory complication within 7 days after surgery. In 6.5% and 1.6% of cases, early postoperative desaturation to < 90% and 80% occurred. Compared to CA2/3 residents, CA1 residents had higher odds of experiencing early postoperative desaturation to < 90% and 80% (adjusted odds ratio [ORadj], 1.07; 95%CI 1.03-1.12; p = 0.002, and ORadj 1.10; 95%CI 1.01-1.20; p = 0.037, respectively). The change in postoperative desaturation rate during the transition from CA1 to CA2/3 status varied substantially from ORadj 0.80 (decreased risk) to 1.33 (increased risk). Major respiratory complication did not differ between experience levels (p = 0.52). However, a strong decline in improvement regarding the rate of postoperative desaturation during the transition from CA1 to CA2/3, was paralleled by an increased odds of major respiratory complication for CA2/3 residents (ORadj 1.20; 95%CI 1.02-1.42; p = 0.026, p-for-interaction = 0.056). Patients treated by CA1 residents have an increased risk of postoperative desaturation. Some residents show an improvement and others a decline in postoperative desaturation rate. Our secondary analysis suggests that there should be more focus on those residents who had a declining performance in postoperative desaturation despite becoming more experienced.


Relationships between the pituitary-adrenal hormones, insulin, and glucose in middle-aged men: moderating influence of psychosocial stress.
We examined whether the relationships between the pituitary-adrenal hormones (corticotropin [ACTH) and cortisol), insulin, and glucose differ as a function of psychosocial stress defined in terms of vital exhaustion (VE) and depressive behavior (DB). The participants were 69 normotensive and 21 unmedicated borderline hypertensive (BH) middle-aged men whose work is stressful. Hormonal and metabolic variables were measured during an oral glucose tolerance test (OGTT), and the cortisol response to dexamethasone (DXM) suppression and intravenous ACTH stimulation was also measured. We found that the basal ACTH level during the OGTT was positively associated with the cortisol response to ACTH at 60 minutes, the fasting insulin level, and the insulin to glucose ratio among exhausted and high DB men, while the reverse was true for nonexhausted and low DB men. Also, a high cortisol response to ACTH, a low cortisol level during the OGTT, and a high ratio of these cortisol determinations (cortisol ratio) were associated with high fasting insulin and glucose levels, the summed insulin values, and the insulin to glucose ratio only among nonexhausted and low DB men; among exhausted and high DB men, these associations were less pronounced, absent, or in the opposite direction. The findings suggest that VE and DB have a moderating influence on the relationships among the hormonal and metabolic parameters studied. Psychosocial stress may affect the pituitary-adrenocortical system in complex ways, contributing thereby to insulin resistance, hyperinsulinemia, and coronary heart disease (CHD) risk.


Ischemia-induced neuronal cell loss is associated with loss of atypical angiotensin type-1 receptor expression in the gerbil hippocampal formation.
The hippocampal formation of Mongolian gerbils expresses high amounts of atypical angiotensin II type-1 receptors. We studied the expression of these receptors by in situ hybridization using specific [35S]-labeled riboprobes and by receptor autoradiography using [125I]Sarcosine1-angiotensin II. Angiotensin II receptor mRNA was found in the pyramidal cell layer of the CA1, CA2 and CA3 subfields, with the highest expression in the CA2 subfield, and in the granular cell layer of the dentate gyrus. Angiotensin II binding was detected in the stratum oriens and stratum radiatum of the CA1 and CA2 subfields, in the stratum oriens of the CA3 subfield, and in the molecular layer of the dentate gyrus. We then studied the effect of ischemia on hippocampal angiotensin II receptor expression, 1, 4 and 15 days after bilateral occlusion of the common carotid arteries for 5 min. No changes in angiotensin II receptor mRNA or binding were detected 1 day after ischemia. Delayed, progressive loss of angiotensin II mRNA and binding occurred 4 and 15 days after ischemia, in the CA1, CA2 and CA3 subfields. The decline was faster in the CA1 subfield, and paralleled the loss of neurons after ischemia. In the dentate gyrus, angiotensin II receptor mRNA and angiotensin II binding were not changed when compared to sham operated controls. The decrease of angiotensin II receptor expression may reflect the loss of angiotensin II receptor-producing neurons rather than a down-regulation of receptor expression.


Prenatal and early diagnosis of Chinese 3-M syndrome patients with novel pathogenic variants.
3-M syndrome is a clinically recognizable yet under-diagnosed primordial growth retardation disorder. Molecular testing for CUL7, OBSL1 or CCDC8 genes can provide confirmed diagnosis for patients at prenatal or early age. So far, the clinical and molecular features of Chinese 3-M syndrome patients have not been reported. In this article, the authors performed prenatal and early diagnosis of Chinese patients with 3-M syndrome by Next-Generation Sequencing. The authors reported six unrelated Chinese 3-M syndrome patients. Five of the six patients were diagnosed before two years of age including one prenatal case. The authors identified six novel pathogenic variants and five previously reported pathogenic variants. The authors' clinical evaluations indicated that Chinese 3-M syndrome patients share similar recognizable features as those reported in patients of other ethnic background. The authors noticed some uncommon features in this small cohort of Chinese patients such as delayed motor development at early ages, undelayed bone age and presence of lower eyelid fat pads. The authors' study of Chinese 3-M syndrome patients revealed novel mutations and clinical phenotypes.


The effects of oxytocin and its analog, carbetocin, on genetic deficits in sensorimotor gating.
Converging evidence from preclinical and clinical studies suggest that oxytocin has therapeutic potential for schizophrenia and other neuropsychiatric disorders. Prepulse inhibition of the startle reflex (PPI) is a measure of sensorimotor gating, an important brain function involved in filtering environmental information. We previously demonstrated that systemically administered oxytocin reversed psychostimulant-induced PPI deficits in rats suggesting that oxytocin can produce antipsychotic-like central effects. That finding was supported by a recent trial in humans, which found that intranasal oxytocin reduced symptoms of schizophrenia. The goal of this study was to extend this line of investigation by testing the effects of oxytocin, and a structural analog of oxytocin, carbetocin, on non-pharmacological deficits in PPI. In experiment 1, Brown Norway (BN) rats, a rat strain that has naturally low PPI, were given either saline or one of three doses of oxytocin (0.04-1.0 mg/kg, sc). In experiment 2, BN rats were given either saline, one of three doses of carbetocin (0.04-1.0 mg/kg) or oxytocin (1 mg/kg). PPI and acoustic startle response (ASR) of rats were tested. Oxytocin significantly increased PPI (P<0.01) and decreased ASR levels (P<0.01) in BN rats in a dose-dependent fashion. In contrast, carbetocin had no effect on PPI levels or ASR. The facilitation of BN PPI by oxytocin is similar to what we have previously observed with clozapine and thus further supports oxytocin having antipsychotic properties. In contrast to oxytocin, our data do not support the use of carbetocin as an antipsychotic drug.


Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C.
Data on the long-term outcome of nonalcoholic steatohepatitis (NASH)-associated cirrhosis are few, and most reports describe cases of cryptogenic cirrhosis associated with risk factors for NASH but without histologic definition. In this prospective cohort study, we describe the long-term morbidity and mortality of 23 patients with NASH-associated cirrhosis defined by strict clinicopathologic criteria. Outcomes were compared with 46 age- and gender-matched patients with cirrhosis from chronic hepatitis C virus (HCV) infection: 23 untreated and 23 nonresponders to antiviral therapy. During follow-up (mean, 84 months; median, 60 months; range, 5-177 months), 9 of the 23 NASH-associated cirrhosis cases developed liver-related morbidity (8 ascites and/or encephalopathy, 1 variceal bleeding). The probability of complication-free survival was 83%, 77%, and 48% at 1, 3, and 10 years, respectively, and the cumulative probability of overall survival was 95%, 90%, and 84% at 1, 3, and 10 years, respectively. Five deaths were from liver failure, 1 from a non-liver-related cause. By multivariate analysis, bilirubin (P =.02) and platelet (P =.04) were independent predictors of complication-free survival; bilirubin (P =.05) was the only predictor for overall survival. After controlling for these factors, there was no difference in complication-free or overall survival between the NASH-cirrhosis cohort and either group of HCV-cirrhosis. However, 8 cases of liver cancer occurred in the HCV-cirrhosis groups compared with none among NASH cases. In conclusion, liver failure is the main cause of morbidity and mortality in NASH-associated cirrhosis. The prognosis is either similar or less severe than HCV-cirrhosis, except that HCC appears less common.


Quantitative analysis of carotid artery Doppler spectral waveforms: diagnostic value of parameters.
Continuous-wave ultrasonic Doppler recordings made at the carotid bifurcation have been processed by spectrum analysis and off-line microprocessor software. Data reduction algorithms were defined and tested prior to incorporation in an integrated, hard-wired device. Subsequent analysis of waveforms in real-time provided measures of peak and mode frequencies and degree of spectral broadening. Correlation of results with 123 angiographically visualized internal carotid arteries showed that peak and mode frequencies generally increased with degree of stenosis while the systolic window decreased. Ratios of peak and mode frequencies in the proximal to the distal internal carotid artery and the systolic window at the distal internal carotid artery were retrospectively found to have diagnostic value with a combination of these three parameters providing the best overall accuracy.


The Challenges of Being Physically Active: A Qualitative Study of Young People With Type 1 Diabetes and Their Parents.
Benefits of physical activity are well recognized for youth with type 1 diabetes mellitus (T1DM), but being active is challenging. In this study, we aimed to investigate the challenges experienced by adolescents, their parents and young adults with T1DM when they are physically active. Six focus groups involving adolescents (13 to 18 years old, n=14) and young adults (19 to 25 years old, n=7) and 4 focus groups with parents (n=14) of the adolescents (13 to 18 years) were established. Data were analyzed using content analysis. Adolescents and young adults with T1DM identified challenges of unpredictability, knowledge, trust and stigma when they were physically active. Parent challenges were specifically unpredictability and trust. Interventions are needed that provide adolescents and young adults with T1DM and parents of adolescents with T1DM more in-depth information about managing physical activity in a manner that enhances their perceived competence and builds autonomy. Interventions can also target peer and community support.


Trends in inpatient care for psychiatric disorders in NHS hospitals across England, 1998/99-2019/20: an observational time series analysis.
It is unclear how hospitals are responding to the mental health needs of the population in England, against a backdrop of diminishing resources. We aimed to document patterns in hospital activity by psychiatric disorder and how these have changed over the last 22 years. In this observational time series analysis, we used routinely collected data on all NHS hospitals in England from 1998/99 to 2019/20. Trends in hospital admissions and bed days for psychiatric disorders were smoothed using negative binomial regression models with year as the exposure and rates (per 1000 person-years) as the outcome. When linear trends were not appropriate, we fitted segmented negative binomial regression models with one change-point. We stratified by gender and age group [children (0-14 years); adults (15 years +)]. Hospital admission rates and bed days for all psychiatric disorders decreased by 28.4 and 38.3%, respectively. Trends were not uniform across psychiatric disorders or age groups. Admission rates mainly decreased over time, except for anxiety and eating disorders which doubled over the 22-year period, significantly increasing by 2.9% (AAPC = 2.88; 95% CI: 2.61-3.16; p < 0.001) and 3.4% (AAPC = 3.44; 95% CI: 3.04-3.85; p < 0.001) each year. Inpatient hospital activity among children showed more increasing and pronounced trends than adults, including an increase of 212.9% for depression, despite a 63.8% reduction for adults with depression during the same period. In the last 22 years, there have been overall reductions in hospital activity for psychiatric disorders. However, some disorders showed pronounced increases, pointing to areas of growing need for inpatient psychiatric care, especially among children.


Taraxacum mongolicum protects against Staphylococcus aureus-infected mastitis by exerting anti-inflammatory role via TLR2-NF-κB/MAPKs pathways in mice.
As a traditional Chinese medicine, Taraxacum mongolicum has been widely used for the prevention and treatment of a variety of inflammatory and infectious diseases, and also clinically used as a remedy for mastitis. However, the scientific rationale and mechanism behind its use on mastitis in vivo are still unclear. This study aimed to investigate the protective effect and potential mechanism of Taraxacum mongolicum Hand.-Mazz. (T. mongolicum) on mastitis infected by Staphylococcus aureus (S. aureus). Female ICR mice were given intragastrically 2.5, 5 and 10 g/kg of T. mongolicum extract twice per day for 6 consecutive days, and infected with S. aureus via teat canal to induce mastitis. Pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels were determined by ELISA. Myeloperoxidase (MPO) activity and distribution were measured by reagent kit and immunohistochemistry. Histopathological changes of mammary gland tissues were observed by H&E staining. Toll-like receptor 2 (TLR2) expression, phosphorylations of related proteins in nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways were detected by western blot. T. mongolicum decreased TNF-α, IL-6 and IL-1β levels, and reduced MPO activity and distribution in sera and mammary glands with S. aureus-infected mastitis. In addition, T. mongolicum effectively attenuated histopathological damages and cell necrosis of mammary gland tissues infected by S. aureus. Moreover, T. mongolicum inhibited the expression of TLR2, and the phosphorylations of inhibitor κBα (IκBα), p65, p38, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) proteins in mammary glands with S. aureus-infected mastitis. This study suggests that T. mongolicum protects against S. aureus-infected mastitis by exerting anti-inflammatory role, which is attributed to the inhibition of TLR2-NF-κB/MAPKs pathways.


Primary Extranodal Lymphoma of the Thorax.
Primary pulmonary lymphomas represent a pathologically heterogeneous group of disorders that often share imaging features, which include peribronchovascular nodules and masses or areas of nonresolving consolidation. Primary mediastinal B-cell lymphoma is an extranodal non-Hodgkin lymphoma seen in younger patients that has imaging and pathologic features that demonstrate some degree of overlap with Hodgkin lymphoma. Primary lymphomas of the pleural space are rare and associated with concomitant viral infections.


Effective fingerprint recognition technique using doped yttrium aluminate nano phosphor material.
First time the yttrium aluminate nanoparticles are used to improve the fingerprint quality. Eco-friendly green combustion process is used to synthesize YAlO3:Sm(3+) (0.5-11mol%) nanophosphor using green tea leaf extract as non-toxic and eco-friendly fuel. Powder X-ray diffraction study confirms the orthorhombic phase. The average sizes of the crystallites were found to be in the range 20-35nm. The emission peaks centered at 564, 601 and 647nm is attributed to 4f-4f (4)G5/2→(6)HJ=5/2,7/2,9/2 forbidden transitions of Sm(3+) ions. Judd-Ofelt theory is applied to experimental data for providing qualitative support by determining J-O intensity parameters. The Commission International De I-Eclairage chromaticity co-ordinates are very close to National Television System Committee standard value of white emission (x=0.296, y=0.237). Further, correlated color temperature is found to be ∼11,900K. A simple, fast, highly sensitive and low-cost method for the detection and enhancement of fingermarks in a broad range of surfaces is developed and constitutes an alternative to traditional luminescent powders.


Activity standardisation of 210Pb by 4πα liquid scintillation counting method.
The activity of 210Pb in a solution with 210Pb-210Po in the radioactive equilibrium was determined through its decay product 210Po by liquid scintillation counting (LSC), which has, after separation, as a pure α emitting nuclide, detection efficiency practically equal to 1. For the separation of 210Po from 210Pb solution, two methods based on precipitation of Pb, and Pb with Bi, leaving Po in the solution, were introduced. The first one was precipitation of Pb in the form of Pb(NO3)2 from a mixture of acetic acid, toluene, water and HNO3. The second one was based on co-precipitation of Bi and Pb with KCl from a mixture of organic solvents, where 210Bi with 210Pb was fixed to the precipitate. The relative standard uncertainty of 210Pb activity concentration was estimated to be lower than 0.45%.


An open-label prospective study to assess short incubation time white LED light photodynamic therapy in the treatment of superficial basal cell carcinoma.
Artificial white LED light photodynamic therapy (awl-PDT) is an effective, pain-free treatment for actinic keratosis. The efficacy of awl-PDT in the treatment of superficial basal cell carcinoma (sBCC) has not been assessed. Patients with histologically confirmed sBCC underwent two treatments of awl-PDT 1 week apart. Lesions were incubated with methyl 5-aminolaevulinic acid for 30 min and then illuminated using the Maquet Power LED 500 theatre light (405-800nm, 140 000 lux) to deliver an equivalent red light dose of 75 J/cm2 at a rate of 55 mW/cm2 . Pain was measured using a visual analogue scale during treatment. Clinical response was assessed at day 28. Follow-up continued 3 months for 1 year. Cosmetic outcome was assessed at 3 months and 1 year. Twenty-eight patients with 36 lesions and a mean age of 63.64 (SD 2.62) were recruited. The median lesion size was 15 mm (IQR 8.75). The response rate at day 28 was 100%. Recurrence rates were 3/36 (8.3%) at 3 months, 6/36 (16.7%) at 6 months, 10/36 (27.8%) at 9 months and 11/36 (30.6%) at 1 year. Median pain scores were 0/100 (IQR 0) and 0/100 (IQR 5) during treatments one and two, respectively. Cosmetic outcome was excellent or good in the majority of cases. Although initially effective for sBCC at 28 days, 30.6% of lesions recurred 1 year after awl-PDT. Pain scores were negligible, and the cosmetic outcome was favourable. Further head-to-head studies with optimised protocols are required to determine if awl-PDT has a role in the treatment of sBCC.


Absence of high-risk human papilloma virus in p16 positive inverted sinonasal papilloma.
Sinonasal inverted papilloma (SIP) is a relatively rare disease, and its etiology is not understood. It is characterized by locally aggressive growth and a strong tendency to recur despite its benign histology. The aim of this study was to identify the presence of human papilloma virus (HPV) and its surrogate marker p16 in SIP tissue samples from a regional cohort. Subjects were identified from our regional center cohort of 88 SIP patients treated between 1984-2014. From these subjects, 54 were included in this study. Of these, 53 biopsies were analyzed with PCR, and 54 samples were immunohistochemically stained for p16. DNA was extracted from histopathologically verified SIP. Genotype screening for 13 high risk-, 5 oncogenic and 6 low risk HPV types was performed using the PapilloCheck® HPV-screening test. HPV analysis was successful for 38 of 53 samples. Of the 38 successfully analyzed samples, only 2 samples were positive for HPV 11. Notably, p16 was present in the epithelia in all samples, and in the papilloma lesions in 37 samples. Since only 2 out of 38 SIPs were positive for HPV (type 11), and at the same time p16 was positive in epithelia in all samples and in 37 of 38 papilloma lesions of the samples, it is concluded that p16 cannot be used as a surrogate marker for high-risk HPV-infection in SIP. We are currently planning a prospective, multicenter study in order to increase the study power and in order to be able to better evaluate the clinical implications of HPV-and p16 in SIP.


Red nucleus lesions delay the evolution of amygdala kindling in cats.
There are some papers which claim that the red nucleus (RN) is related to epileptic manifestations. Though the lesion or electrographic recording of the RN include many paths which assemble into it, the possibility that its cells are implicated in epilepsy is deduced. This paper compares the evolution of amygdaloid kindling in cats with bilateral RN lesions, with the epileptic disturbances provoked by lesion or stimulation of approach cells. Due to the intrinsic error of the stereotaxic method, only 7 of 13 cats show lesions in the RN with a diameter extending down to 150 micron. Only these show a shortening of the afterdischarge duration, a delay in the appearance of the consecutive clinical stages, and a lengthening in the appearance of generalized tonic-clonic seizures. In comparison, the 6 other cats show lesions mainly in the adjacent central tegmental field, and their kindling evolution was similar to that of a control group with intact mesencephalon. We conclude that the RN lesions interfere with the kindling generation, presumably by lesioning the cerebello-cerebral paths which produce a depression of cortical activity, during the consolidation of clinical and electrographic manifestations.


Transcriptomic analysis of intestinal fibrosis-associated gene expression in response to medical therapy in Crohn's disease.
Glucocorticoids and monoclonal antibodies to tumor necrosis factor reduce inflammation in Crohn's disease (CD). Rapid luminal healing, however, may promote intestinal stricture formation. The aim of this study was to examine fibrosis-associated gene expression in the intestine of patients with CD and correlate expression levels with prior medical therapies. In all, 37 patients with stricturing CD and 18 non-CD controls underwent a transmural biopsy at the time of elective intestinal resection. Quantitative real-time polymerase chain reaction (PCR) was conducted to determine differential mRNA expression of TGF-beta(1), Smad-7, CTGF, collagen-1alpha, fibronectin, BMP-7, and MIF. Intestinal fibroblasts were treated in vitro with dexamethasone. Relative to control, strictured CD intestinal tissue expressed increased TGF-beta(1), CTGF, collagen-1alpha, and BMP-7 (all P < 0.05). TGF-beta(1) gene expression positively correlated with the expression of its downstream targets (all P < 0.001). Preoperative infliximab exposure was not associated with increased expression in any of the target genes nor did the number of infliximab infusions correlate with gene expression. The number of cycles of corticosteroid treatment preoperatively was positively associated with CTGF (r = 0.486, P = 0.016) and MIF (r = 0.524, P = 0.009) expression. Intestinal fibroblasts treated in vitro with dexamethasone upregulated CTGF expression (P = 0.023). Exposure to infliximab does not appear to induce a profibrotic transcriptional response in the CD intestine. Previous corticosteroid treatment is associated with increased expression of CTGF and MIF. Treating intestinal fibroblasts in vitro with steroids upregulates CTGF expression.


The effect of a retrieval cue on the return of spider fear.
Exposure therapy is often used as treatment for anxiety disorders. However, a change in context after exposure can result in fear renewal. This renewal can be attenuated by using retrieval cues stemming from the exposure context. The present study investigated the effect of such a cue in spider-fearful persons. Thirty-three participants underwent an in vivo exposure session while wearing a bracelet (retrieval cue). After exposure, half of the participants continued to wear the bracelet at home until follow-up (cue groups); the other half handed over the bracelet after exposure (no cue groups). Half of the participants in each group received the follow-up in the exposure context (AAcue and AAnocue); for the other half follow-up was conducted in a novel environment (ABcue and ABnocue). A switch in context at follow-up resulted in more self-reported anxiety and arousal compared to no switch. However, the retrieval cue did not attenuate this renewed responding. The number of participant per condition was limited, which might have obscured possible retrieval cue effects due to a lack of power. Additionally, information about the retrieval cue was provided after exposure, which might have weakened the association between the cue and exposure therapy. Furthermore, no autonomic measures were incorporated, restricting the effect to self-report measures. For future studies we would recommend to explicitly link the retrieval cue before onset of the exposure session and to incorporate autonomic measures. Our findings indicate that a switch in context resulted in more self-reported anxiety and arousal, but that a cue stemming from the exposure context did not attenuate this renewal.


Visualization of localized elastic properties in human tooth and jawbone as revealed by scanning acoustic microscopy.
The elastic properties of human canine and supporting alveolar bone are measured by the distribution of localized speed of sound using scanning acoustic microscopy. Methods for the dynamic, non-destructive diagnostics of dental hard tissues can have a key role in the early detection of demineralization processes and carious lesions, and they are supposed to open the possibility of early dental restorations. The localized distribution of the ultrasound velocity in canine tooth and alveolar bone was obtained using scanning acoustic microscopy with a 5- and 30-MHz transducer. An acoustic material signature curve signifies the interference of the waves and quantitatively maps the localized speed of sound in alveolar bone and the canine tooth. Seven samples, consisting of alveolar jawbone and tooth sliced along the coronally apical axis, were investigated. The average speed of sound was determined along three independent cross sections at enamel, dentin and cortical bone. The average speed of sound in enamel, bone and dentin was SD 3460 ± 193 m/s, 3232 ± 113 m/s and 2928 ± 106 m/s. The distribution of sound wave propagation reveals a decrease in sound speed from the peripheral parts within the enamel and dentin layers toward the proximal zones. These results prove the possibility of linking the elastic properties to different areas within the osseous and dental hard tissues and visualize them in an extremely high local resolution. The results serve as a basis for further study and substantiate the enormous potential of ultrasound based analysis in the field of dento-alveolar diagnosis.


Testicular epidermoid cyst: a case report and review of the clinicopathologic features.
Epidermoid cysts of the testicle are rare, benign lesions that are clinically indistinguishable from malignant germ cell tumors. A scrotal mass in a 27-year-old man was incidentally detected by his family physician, and confirmed to be intratesticular by ultrasound. Radical orchidectomy was performed revealing the pathologic diagnosis. The presentation, evaluation and management of epidermoid cysts are discussed.


Purification and kinetic characteristics of strombine dehydrogenase from the foot muscle of the hard clam (Meretrix lusoria).
Strombine dehydrogenase (SDH, EC 220.127.116.11) from the foot of the hard clam Meretrix lusoria was purified over 470-fold to apparent homogeneity. It has a monomeric structure with a relative molecular mass of 46,000. Two isoenzymes were identified with isoelectric points of 6.83 and 6.88. SDH is heat labile, and has pH and temperature optima of 7.4-7.6 and 45-46°C, respectively. l-Alanine, glycine, and pyruvate are the preferred substrates. l-Serine is the third preferred amino acid. Iminodiacetate with the lowest K(i) of SDH at both pH 6.5 and 7.5 was the strongest inhibitor among succinate, acetate, iminodiacetate, oxaloacetate, and l-/d-lactate. The inhibitory activities of succinate at pH 6.5, and iminodiacetate and oxaloacetate at pH 7.5 on the SDH were higher. These inhibitors are either competitive or mixed-competitive inhibitors. Half of the enzymatic activity of SDH was inhibited by 0.2mM Fe(3+) and 0.6mM Zn(2+).


Transsexualism and anatomic sex ratio reversal in Poland.
Transsexualism has been described in numerous papers as a condition appearing, on the average, four times as often with somatic males than with somatic females. Against this background we consider the situation in Poland, where, during three consecutive observation cycles over 6 years, the results obtained were reversed. Among our transsexuals the ratio was 5.5:1, with the majority being somatic females.


Spontaneous recanalization of carotid artery occlusion following non traumatic dissection.
We studied 7 patients with internal carotid occlusion following spontaneous arterial dissection. All presented strokes, in one associated with Horner's syndrome. The doppler examination showed carotid occlusion, but only angiography established the diagnosis of vascular disease. Spontaneous recanalization was observed in 6 cases, treated only by antiplatelet drugs.


Is heart failure with midrange ejection fraction similar to preserved ejection fraction? Against.
The new European guidelines (2016) for heart failure (HF) include the concept of HF with intermediate left ventricular ejection fraction (LVEF), i.e. an LVEF between 40 and 49%. Although few studies have been carried out, there are claims that HF with intermediate LVEF is not the same as HF with preserved LVEF. Perhaps the most consistent claim is the high percentage of associated ischemic heart disease, which could reflect LVEF recovery after adequate anti-ischemic treatment of HF with depressed LVEF, or even the progressive deterioration of LVEF following an ischemic event.


The prevalence of self-harm behaviors among a sample of gastric surgery candidates.
The surgical treatment of obesity is becoming increasingly popular; yet, little is known about the self-harm characteristics and adjunctive self-regulation difficulties of those seeking such surgery. In the literature, one study has explored presurgery suicide attempts and several studies have explored the prevalence of postsurgical completed suicides. However, beyond suicide attempts and completions, little is known about the broader self-harm/self-regulation profiles of these patients. In this study, we examined the prevalence of 22 such behaviors among a sample of gastric surgery candidates. Using a cross-sectional approach, we examined 121 surgical candidates for 22 self-reported self-harm and self-regulatory behaviors. The studied behaviors with the highest prevalence rates in this cohort were sexual promiscuity (22.3%), torturing oneself with self-defeating thoughts (20.7%), alcohol abuse (19.0%), and engaging in emotionally abusive relationships (16.5%). With regard to suicide attempts, 9.1% of participants acknowledged a history and 9.1% reported past overdoses. These data suggest that (a) adjunctive self-regulatory difficulties may affect a substantial minority of individuals who are seeking gastric surgery for obesity (e.g., promiscuity and alcohol abuse), and (b) the anticipated prevalence rate for past suicide attempts in this population appears to be approximately 10%.


Utility of BRAF V600E immunohistochemistry in the diagnosis of mandibular ameloblastomas.
Ameloblastoma, odontogenic keratocyst (OKC), and dentigerous cyst (DC) can have similar radiographic and histological appearances. The purpose of this study was to determine the utility of BRAF immunohistochemistry in discerning mandibular ameloblastomas from OKCs and DCs. This retrospective cohort study included patients treated between 1998 and 2018. Inclusion criteria include incisional biopsy-proven mandibular ameloblastoma, OKC, or DC, and sufficient tissue for immunohistochemistry. The primary predictor variable was the type of lesion. The primary outcome variable was the presence/absence of BRAF V600E immunoreactivity. The cohort consisted of 43 patients (19 female, 24 male; mean age 48 ± 17 years). There were 22 ameloblastomas, 11 OKCs, and 10 DCs. Among ameloblastomas, 68.2% (15/22) stained positive for BRAF V600E; no OKC or DC was positive (P < 0.001). By subtype, the majority of the follicular (83.3%), unicystic (83.3%), desmoplastic (66.7%), and acanthomatous (100%) subtypes were positive, but only 33.3% of the plexiform subtype were positive. BRAF immunohistochemistry may be a useful adjunct in the differentiation of ameloblastoma from OKCs and DCs on incisional biopsies. It may be particularly useful for small samples with a prominent cystic component or equivocal histopathology. Mandibular lesions that are BRAF immunohistochemistry positive are unlikely to be DCs or OKCs.


Trauma patients returning to the emergency department after discharge.
While readmission rates of trauma patients are well described, little has been reported on rates of re-presentation to the emergency department (ED) after discharge. This study aimed to determine rates and contributing factors of re-presentation of trauma patients to the ED. One-year retrospective analysis of discharged adult trauma patients at a county-funded safety-net level one trauma center. Of 1416 trauma patients, 195 (13.8%) re-presented to the ED within 30 days. Of those that re-presented, 47 (24.1%) were re-admitted (3.3% overall). The most common reasons for re-presentation were pain control and wound complications. Patients with Medicare (AOR 2.6, 95% CI 1.3 to 5.2) or other government insurance (AOR 2.5, 95% CI 1.6 to 4.1) were more likely to re-present than patients with private insurance. A considerable number of trauma patients re-presented to the ED after discharge for reasons that did not require hospitalization. Discharge planning for certain vulnerable groups should emphasize wound care, pain control and scheduled follow-up to decrease the reliance on the ED.


Randomized trial of neoadjuvant therapy for lung cancer: interim analysis.
The role of neoadjuvant chemotherapy in stage IIIa non-small cell lung cancer remains undefined. Since 1987, 27 patients with non-small cell lung cancer, all with histologically confirmed metastases to the ipsilateral mediastinal lymph nodes, have been enrolled in an ongoing prospective, randomized trial at our institution. Thirteen patients have been randomized to preoperative etoposide-platinum (EP) chemotherapy-surgery-postoperative EP, and 14 other patients have been randomized to surgery-postoperative mediastinal irradiation (SRT). Both groups are similar in sex, age, weight loss, tumor location, preoperative pulmonary function, physiologic grade, and tumor histology. Eight of the 13 EP patients have responded as evidenced by a 50% or greater radiographic tumor shrinkage after two cycles. Complete tumor and nodal resection rates were similar: 11/13 EP patients versus 12/14 SRT patients. There was no operative mortality for the 27 patients. Median potential follow-up is 29.9 months for the EP group and 34.9 months for the SRT group. Preliminary results suggest a trend toward increased survival time for the EP group (median, 28.7 months) versus the SRT group (median, 15.6 months) (p2 = 0.095). Eleven of 12 resected SRT patients have had recurrence versus 8 of 11 resected EP patients. Time to recurrence reveals no significant differences between the two groups but a trend toward increased disease-free interval in the EP group (12.7 months versus 5.8 months, EP versus SRT). This interim analysis demonstrates the feasibility of such a trial; however, despite the trends, definitive conclusions await further accrual and study maturation.


Physicochemical characterization and tissue distribution of esterases in two salamandridae species (Mertensiella luschani and Salamandra salamandra).
1. Tissue- and species-specificity of the electrophoretic patterns of the multiple molecular forms of esterases were observed in the urodele amphibians Mertensiella luschani luschani, M.l. helverseni and Salamandra salamandra. All esterases--distributed into two electrophoretic mobility areas in gonads, muscles and brain and into four areas in liver, stomach and intestine--were characterized as carboxylesterases. 2. M. l. luschani and S. salamandra liver esterases were electrofocused into nine and eleven major bands with pIs ranging from 4.60 to 5.65 and from 4.40 to 6.20, respectively. 3. Two size groups of esterases were observed in liver extracts of the above three subspecies by Sephadex G-200 gel filtration. The mean values of their apparent molecular weights were 70,000 and 230,000 respectively.


Family history of diabetes and the risk of subclinical atherosclerosis.
This study investigated the influence of a family history of diabetes on the risk of subclinical coronary atherosclerosis according to coronary computed tomography angiography (CCTA) in asymptomatic individuals. A total of 6434 consecutive asymptomatic individuals with no prior history of coronary artery disease voluntarily underwent CCTA evaluation as part of a general health examination. Coronary atherosclerotic plaque and significant coronary artery stenosis (degree of stenosis ≥50%) on CCTA were assessed. Logistic regression analysis was used to determine the association between a family history of diabetes and atherosclerotic plaque or significant coronary artery stenosis according to the degree of diabetes (normal, prediabetic and diabetic). Mean age of study participants was 53.7±7.6 years, and 4694 (73.0%) were male. A total of 1593 (24.8%) participants had a family history of diabetes in a first-degree relative. Among the study participants, 1115 (17.3%), 3122 (48.5%) and 2197 (34.1%) were categorized as diabetic, prediabetic and normal, respectively. In diabetic participants, after stepwise adjustments for clinical and laboratory variables, a family history of diabetes was significantly associated with non-calcified plaque (P<0.05 for all), but did not appear to be associated with either calcified or mixed plaques or with significant coronary artery stenosis (P>0.05 for all). In prediabetic and normal participants, a family history of diabetes was not associated with either atherosclerotic plaque or significant coronary artery stenosis (P>0.05 for all). In asymptomatic diabetic individuals, a family history of diabetes is consistently associated with non-calcified coronary plaque after adjusting for risk factors.


Continuous immobilized yeast reactor system for complete beer fermentation using spent grains and corncobs as carrier materials.
Despite extensive research carried out in the last few decades, continuous beer fermentation has not yet managed to outperform the traditional batch technology. An industrial breakthrough in favour of continuous brewing using immobilized yeast could be expected only on achievement of the following process characteristics: simple design, low investment costs, flexible operation, effective process control and good product quality. The application of cheap carrier materials of by-product origin could significantly lower the investment costs of continuous fermentation systems. This work deals with a complete continuous beer fermentation system consisting of a main fermentation reactor (gas-lift) and a maturation reactor (packed-bed) containing yeast immobilized on spent grains and corncobs, respectively. The suitability of cheap carrier materials for long-term continuous brewing was proved. It was found that by fine tuning of process parameters (residence time, aeration) it was possible to adjust the flavour profile of the final product. Consumers considered the continuously fermented beer to be of a regular quality. Analytical and sensorial profiles of both continuously and batch fermented beers were compared.


Long-term satisfaction of patients after laparoscopic and robotic-assisted hysterectomy.
Da-Vinci-Xi is the most recent device used in gynecologic robotic surgery. The aim of the present study was to compare the long-term satisfaction of patients who had undergone conventional laparoscopic hysterectomy or robotic assisted laparoscopic hysterectomy using the Da-Vinci-Xi surgical system. All hysterectomies performed at the University Hospital of Luebeck from 2018 to 2019 were reviewed. Postoperative outcomes were compared between women who had undergone total hysterectomy with da Vinci Xi (n = 42) or conventional laparoscopy (n = 97). Postoperative outcomes included pain, elimination of complaints after surgery, bladder function, sexual function, satisfaction with the cosmetic outcome, positive experiences after robotic surgery, and satisfaction with the surgeon's preoperative explanation. Obese patients were evaluated separately in a subgroup analysis. Both groups had similar baseline characteristics and complication rates. Preoperative complaints subsided after surgery in a little more than 90% of patients. No significant differences were noted between groups in this regard (p = 0.262), or with reference to postoperative pain after one week (p = 0.866) and one month (p = 0.580), stress incontinence (p = 0.343), sexual function (p = 0.766) and the cosmetic outcome of the abdominal incisions (p = 0.273). The majority of patients who had undergone robotic surgery (96.8%) would be willing to undergo the procedure again if necessary. The subgroup analysis of obese patients revealed no significant differences. The Da-Vinci-Xi device did not improve the long-term surgical satisfaction of normal-weight or obese patients who underwent hysterectomy compared with patients who underwent conventional laparoscopy performed by experienced laparoscopic surgeons.


Differential second messenger signaling via dopamine neurons bidirectionally regulates memory retention.
Memory formation and forgetting unnecessary memory must be balanced for adaptive animal behavior. While cyclic AMP (cAMP) signaling via dopamine neurons induces memory formation, here we report that cyclic guanine monophosphate (cGMP) signaling via dopamine neurons launches forgetting of unconsolidated memory in Drosophila. Genetic screening and proteomic analyses showed that neural activation induces the complex formation of a histone H3K9 demethylase, Kdm4B, and a GMP synthetase, Bur, which is necessary and sufficient for forgetting unconsolidated memory. Kdm4B/Bur is activated by phosphorylation through NO-dependent cGMP signaling via dopamine neurons, inducing gene expression, including kek2 encoding a presynaptic protein. Accordingly, Kdm4B/Bur activation induced presynaptic changes. Our data demonstrate a link between cGMP signaling and synapses via gene expression in forgetting, suggesting that the opposing functions of memory are orchestrated by distinct signaling via dopamine neurons, which affects synaptic integrity and thus balances animal behavior.


[Metaphors and affect: their interrelation in the therapeutic process].
In accordance with Freud's hypothesis about the nature of primary process thinking we analysed metaphors as possible tools for the integration of unconscious affective und cognitive representational processes which, besides being complementary to affective interactive dyadic behaviour, may be of curative value. Using videotapes of 10 fifteen-hour short-term therapies by very experienced therapists treating an unselected group of patients, facial affect and metaphoric language of the therapist and the patient as well as the temporal distance between the two was recorded. The density of metaphors was not significantly correlated with symptom reduction but with treatment satisfaction. However, symptom reduction correlated significantly with the frequency of interactive metaphors used by both the therapist and the patient. It could be shown that there is an optimal time window between facial affect and metaphor production beyond the here and now, but not as a long term memory.


Effects of external calcium ions and strontium ions on interactions of isoprenaline and its competitive inhibitor with beta-adrenoceptors in the intestinal smooth muscle.
The effects were tested of Ca ions and Sr ions on interactions of isoprenaline and its competitive inhibitor with beta-adrenoceptors in the taenia caecum from the guinea pig. Ca ions were involved in the combination of isoprenaline with the beta-adrenoceptors but not involved in the combination of the competitive inhibitor with the beta-adrenoceptors. Sr ions could not substitute for Ca ions in the isoprenaline--receptor interaction.


Enhancing the grain size of organic halide perovskites by sulfonate-carbon nanotube incorporation in high performance perovskite solar cells.
The grain size of perovskites was enhanced and the grain boundary was filled with sulfonate carbon nanotubes (s-CNTs) during the CH3NH3PbI3 perovskite precursor solution spin-coating process with the incorporation of s-CNTs. The performance of s-CNT incorporated perovskite solar cells remarkably increased from 10.3% to 15.1% (best) compared with pristine CNT incorporated perovskite solar cells.


Distinct roles for the p110alpha and hVPS34 phosphatidylinositol 3'-kinases in vesicular trafficking, regulation of the actin cytoskeleton, and mitogenesis.
We have examined the roles of the p85/ p110alpha and hVPS34 phosphatidylinositol (PI) 3'-kinases in cellular signaling using inhibitory isoform-specific antibodies. We raised anti-hVPS34 and anti-p110alpha antibodies that specifically inhibit recombinant hVPS34 and p110alpha, respectively, in vitro. We used the antibodies to study cellular processes that are sensitive to low-dose wortmannin. The antibodies had distinct effects on the actin cytoskeleton; microinjection of anti-p110alpha antibodies blocked insulin-stimulated ruffling, whereas anti-hVPS34 antibodies had no effect. The antibodies also had different effects on vesicular trafficking. Microinjection of inhibitory anti-hVPS34 antibodies, but not anti-p110alpha antibodies, blocked the transit of internalized PDGF receptors to a perinuclear compartment, and disrupted the localization of the early endosomal protein EEA1. Microinjection of anti-p110alpha antibodies, and to a lesser extent anti-hVPS34 antibodies, reduced the rate of transferrin recycling in CHO cells. Surprisingly, both antibodies inhibited insulin-stimulated DNA synthesis by 80%. Injection of cells with antisense oligonucleotides derived from the hVPS34 sequence also blocked insulin-stimulated DNA synthesis, whereas scrambled oligonucleotides had no effect. Interestingly, the requirement for p110alpha and hVPS34 occurred at different times during the G1-S transition. Our data suggest that different PI 3'-kinases play distinct regulatory roles in the cell, and document an unexpected role for hVPS34 during insulin-stimulated mitogenesis.


Simultaneous multiple-stimulus auditory brain-computer interface with semi-supervised learning and prior probability distribution tuning.
Objective.Auditory brain-computer interfaces (BCIs) enable users to select commands based on the brain activity elicited by auditory stimuli. However, existing auditory BCI paradigms cannot increase the number of available commands without decreasing the selection speed, because each stimulus needs to be presented independently and sequentially under the standard oddball paradigm. To solve this problem, we propose a double-stimulus paradigm that simultaneously presents multiple auditory stimuli.Approach.For addition to an existing auditory BCI paradigm, the best discriminable sound was chosen following a subjective assessment. The new sound was located on the right-hand side and presented simultaneously with an existing sound from the left-hand side. A total of six sounds were used for implementing the auditory BCI with a 6 × 6 letter matrix. We employ semi-supervised learning (SSL) and prior probability distribution tuning to improve the accuracy of the paradigm. The SSL method involved updating of the classifier weights, and their prior probability distributions were adjusted using the following three types of distributions: uniform, empirical, and extended empirical (e-empirical). The performance was evaluated based on the BCI accuracy and information transfer rate (ITR).Main results.The double-stimulus paradigm resulted in a BCI accuracy of 67.89 ± 11.46% and an ITR of 2.67 ± 1.09 bits min-1, in the absence of SSL and with uniform distribution. The proposed combination of SSL with e-empirical distribution improved the BCI accuracy and ITR to 74.59 ± 12.12% and 3.37 ± 1.27 bits min-1, respectively. The event-related potential analysis revealed that contralateral and right-hemispheric dominances contributed to the BCI performance improvement.Significance.Our study demonstrated that a BCI based on multiple simultaneous auditory stimuli, incorporating SSL and e-empirical prior distribution, can increase the number of commands without sacrificing typing speed beyond the acceptable level of accuracy.


Resistance of in vivo-selected spontaneously transformed cells and Rous sarcoma virus-transformed cells to macrophage-mediated cytotoxicity.
The cytotoxic activity (CTA) of activated peritoneal macrophages (MP) on variant lines of Syrian hamster embryo (HE) cells of differing malignant characteristics was studied. The target cells were a line of low-malignant cells resulting from spontaneous transformation of HE cells in vitro (STHE strain), and malignant variants selected from them in vivo (STHE-LM-4, STHE-LM-8, and STHE-75/18 strains). In addition, we used cells of the HET-SR-1 strain; these are HE cells transformed in vitro by a tumorigenic Rous sarcoma virus (Schmidt-Ruppin strain, RSV-SR), or the TU-SR strain induced by RSV-SR in vivo. Thioglycollate-elicited peritoneal MP from Syrian hamsters were activated in vitro with bacterial levan, LPS or MDP and used as effector cells. MP-mediated cytolysis was determined by means of a 42-h radioactivity release assay with 3H-thymidine-labeled target cells. We found that only the parental STHE cells were susceptible towards fully-activated MP-mediated CTA. All three of the in vivo-selected malignant variants of the STHE cell sublines, as well as the tumorigenic RSV-SR transformants, were resistant to cytolysis by activated MP. Non-activated thioglycollate-elicited MP did not lyse any of the tumor cells studied.


Induction therapy of basiliximab versus antithymocyte globulin in renal allograft: a systematic review and meta-analysis.
The aim of this meta-analysis was to evaluate the efficacy of basiliximab versus antithymocyte globulin for induction therapy in renal allograft. Medline (PubMed), Embase, Ovid, Cochrane, and the Chinese Biomedical Literature databases were searched to identify prospective randomized controlled trials that compared basiliximab with antithymocyte globulin (ATG) for induction therapy in renal transplantation. RevMan 5.1 software and Stat Manager V4.1 software were used for the meta-analysis. Eight RCTs were included, including a total of 1153 patients. Of these, 547 (47%) had received basiliximab, and 606 (53%) had received ATG. The pooled results revealed that the basiliximab had a lower rate of neoplasm compared with ATG [odds ratio (OR) 0.26; 95% confidence interval (CI) 0.08-0.78; P = 0.02]. There were no significant differences between the two drugs regarding 1-year acute rejection rate (OR 1.32; 95% CI 0.93-1.87; P = 0.13), 1-year graft survival rate (OR 0.73; 95% CI 0.45-1.18; P = 0.20), 1-year patient survival rate (OR 0.52; 95% CI 0.27-1.02; P = 0.06), 1-year infection rate (OR 0.90; 95% CI 0.48-1.68; P = 0.73). Induction therapy of basiliximab has similar short-time effects on the recipients in renal transplantation compared with that of ATG. However, regarding the long-term effect, as represented by the rate of neoplasm, basiliximab has a significant advantage.


The prognostic role of FZD6 in esophageal squamous cell carcinoma patients.
Esophageal squamous cell carcinoma (ESCC) is a kind of cancer with heterogeneous biological characteristics, which is affected by a complex network of gene interactions. Identification of molecular biomarkers paves the way for individualized therapy based on gene expression profiles, which can overcome the heterogeneity of ESCC. In this study, GSE20347, GSE23400 and GSE45670 datasets were retrieved from Gene Expression Omnibus (GEO) database, and the overlapping differentially expressed genes (DEGs) in three datasets were screened. Then the overlapping DEGs function was annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-enrichment analysis. The prognostic value of the top five KEGG pathway-related genes were further validated in The Cancer Genome Atlas (TCGA) database. After extensive statistical analysis, four genes (CDC25B, CXCL8, FZD6 and MCM4) were identified as potential prognostic markers. Among the four candidate genes, the prognostic value of FZD6 in ESCC patients has not been evaluated. Therefore, we finally used immunohistochemistry method to evaluate the effect of FZD6 on the prognosis of patients with ESCC. Additionally, we detected the expression level of FZD6 in ESCC cell line and normal esophageal epithelial cell line, and observed the cell viability of ESCC cell line after FZD6 knockdown. The results showed that the overexpression of FZD6 predicted poor overall survival (OS) (P = 0.005) and progression-free survival (PFS) (P = 0.004) in ESCC patients. COX regression analysis showed that N stage (P = 0.026) and FZD6 expression level (P = 0.001) were independent prognostic factors of OS for ESCC patients. Furthermore, compared with normal esophageal epithelial cell line, the up-regulation of FZD6 was detected in ESCC cell line. Knockdown of FZD6 could significantly inhibit the proliferation of ESCC cells (P < 0.001). CDC25B, CXCL8, FZD6 and MCM4 were screened as candidate genes for prognosis assessment of patients with ESCC. The prognostic role of FZD6 in ESCC patients was confirmed in current study.


A biomimetic structured bio-based flame retardant coating on flexible polyurethane foam with low smoke release and antibacterial ability.
Flexible polyurethane foam (FPUF) is widely used in our life, but it is inherent flammable. The demand for environmental-friendly multi-functional FPUF has been increasing rapidly in the last decade. In this work, a novel bio-based flame retardant coating was constructed by chemically reacting sodium alginate (OSA) and polydopamine (PDA) on the FPUF, followed by depositing nanorod-like β-FeOOH molecules through complexation reaction to form a biomimetic structure. The limiting oxygen index of the coated FPUF samples reached 25.5%. The peak heat release rate was reduced by 45.0%, and the smoke density of the coated sample was decreased by 69.1% compared to that of the control FPUF sample. It was proposed that the OSA-PDA-β-FeOOH decomposed during combustion to promote the formation of compact crosslinked char and released inert gases to dilute the combustible gases, and the β-FeOOH transferred to Fe2O3 to settled the smoke particles reducing the smoke release. Furthermore, the coating with shark skin like structure endowed FPUF antibacterial ability because of its good superoleophobicity underwater. This work provided a novel strategy to construct a biomimetic multifunctional coating on the FPUF.


Estrogen and antiestrogen interaction with estrogen receptor of MCF-7 cells--relationship between processing and estrogenicity.
Overnight preincubation of MCF-7 cells with 2 x 10(-10) M estradiol (E2) produces a dramatic reduction of their specific [3H]E2 binding capacity. Scatchard plot analysis revealed that this loss of estrogen receptor (ER) concentration, usually termed "processing", occurs without any significant modification of binding properties of the unprocessed receptors. Direct measurement of ER (ER-EIA from Abbott) gave residual receptor concentrations close to those established by binding assay indicating that processing involves the loss of at least one epitope other than the steroid binding site. Incubation with increasing amounts of E2 (0.1 to 5 x 10(-10) M) resulted in an increasing reduction of binding capacity indicating that the extent of processing is associated with the hormone concentration. Steroidal estrogens other than E2 as well as antiestrogens of the triphenylethylene category behaved similarly in this regard although the latter compounds usually acted only when at higher concentrations. The processing capacity of a large series of ligands was compared with the corresponding binding affinity for ER as assessed by classical competitive inhibition of [3H]E2 binding in both cytosol and whole cells. For steroidal estrogens, a large spectrum of concordant values was found which correlated with the known uterotrophic activity of the compounds. On the contrary, weak estrogen and antiestrogens of the triphenylethylene category displayed low processing capacities which were in the order of magnitude of the binding affinities established in whole cells; these values were considerably lower than the corresponding values measured in the cytosol. These observations are consistent with the concept that the capacity of a ligand to process ER is related to its agonistic activity. They also support our hypothesis (J. steroid Biochem. 25 (1986) 677-682) that assessment of the ability of a ligand to inhibit the binding of [3H]E2 in whole cells provides an estimate of its agonistic activity, an estimate which can not be established in the corresponding cytosol assay.


Polysaccharide-protein microparticles based-scaffolds to recover soft tissue loss in mild periodontitis.
Periodontal regeneration is extremely limited and unpredictable due to structural complications, as it requires the simultaneous restoration of different tissues, including cementum, gingiva, bone, and periodontal ligament. In this work, spray-dried microparticles based on green materials (polysaccharides - gums - and a protein - silk fibroin) are proposed to be implanted in the periodontal pocket as 3D scaffolds during non-surgical treatments, to prevent the progression of periodontal disease and to promote the healing in mild periodontitis. Arabic or xanthan gum have been associated to silk fibroin, extracted from Bombyx mori cocoons, and loaded with lysozyme due to its antibacterial properties. The microparticles were prepared by spray-drying and cross-linked by water vapor annealing, inducing the amorphous to semi-crystalline transition of the protein component. The microparticles were characterized in terms of their chemico-physical features (SEM, size distribution, structural characterization - FTIR and SAXS, hydration and degradation properties) and preclinical properties (lysozyme release, antibacterial properties, mucoadhesion, in vitro cells adhesion and proliferation and in vivo safety on a murine incisional wound model). The encouraging preclinical results highlighted that these three-dimensional (3D) microparticles could provide a biocompatible platform able to prevent periodontitis progression and to promote the healing of soft tissues in mild periodontitis.


[Development of idiopathic dacryostenosis (clinical and pathologico-anatomical findings)].
The authors describe microsurgical appearances of tear-sac and nasal mucous membranes from 45 patients suffering from dacryostenosis without clinically manifest nose or sinus conditions. In addition the observations of Henle (1865), that described the continuation of expandible conchal mucous membrane up to the lower part of the tear duct were controlled. The observations gave the following results: 1. In all cases of dacryostenosis there was a past history of more or less severe acute or chronic inflammation of the nasal and tear-duct mucous membrane. 2. The submucose of the ductus naso-lacrimalis surrounded by bone contains arterioles with sphincters and cavernous vessel complexes which can cause swelling up to displacement of the canal lumen, according to the blood flow. The results support the hypothesis of the authors that "idiopathic" dacryostenosis is caused by ascending inflammations from the region of the nose and sinus cavities, which can be clinically quite inconspicuous.


What works for whom? Determining the efficacy and harm of treatments for pain.
There has been a tension between the needs of regulators and industry to demonstrate that interventions are effective and safe, and the needs of professionals to understand how well interventions will work for their patients, and patients to understand what might work for them as individuals. The custom has been to focus on statistical outcomes based on average results, but in-depth analysis based on outcomes obtained by individual patients demonstrates that few are average. Rather, a minority of patients achieve very large reductions in pain (responders), while the majority achieve little (nonresponders). Those who benefit in terms of pain also benefit in other areas, with improved sleep, fatigue, mood, function, quality of life, and ability to work. This changes how benefit and risk are seen; nonresponders should stop treatments that don't work and not, therefore, be exposed to risks, while responders have very large benefits to offset against rare but potentially serious harm. This alternative view, patient-centred and practice-orientated, has major implications for clinical practice, how and why we do clinical trials and how they are designed, how health economic evaluations are done, for decisions made by regulatory and other bodies, and for the theory and practice of evidence-based medicine.


Degradation and mineralization of 2,4,6-trinitroresorcine in various photochemical systems.
Comparison was observed for degradation and mineralization of the explosive 2,4,6-trinitroresorcine (TNR) in different photochemical systems TNR/UV, TNR/UV/TiO2, TNR/UV/H2O2, TNR/UV/O3, TNR/UV/TiO2/H2O2 and TNR/UV/TiO2/O3 using High Performance Liquid Chromatography coupled with Mass Spectrometry (HPLC/MS) and Total Organic Carbon (TOC) analysis. Addition of oxidizing agents such as H2O2 or O3 accelerated the rate of TNR conversion and mineralization. Highest reaction rate was obtained in TNR/UV/TiO2/H2O2 system. The intermediate products were characterized and identified by LS-MS technique. The similarity in intermediate products of TNR suggested the analogous reaction pathways of the TNR degradation by these different systems.


MBP-binding DARPins facilitate the crystallization of an MBP fusion protein.
The production of high-quality crystals is the main bottleneck in determining the structures of proteins using X-ray crystallography. In addition to being recognized as a very effective solubility-enhancing fusion partner, Escherichia coli maltose-binding protein (MBP) has also been successfully employed as a `fixed-arm' crystallization chaperone in more than 100 cases. Here, it is reported that designed ankyrin-repeat proteins (DARPins) that bind with high affinity to MBP can promote the crystallization of an MBP fusion protein when the fusion protein alone fails to produce diffraction-quality crystals. As a proof of principle, three different co-crystal structures of MBP fused to the catalytic domain of human dual-specificity phosphatase 1 in complex with DARPins are reported.


Domain rearrangements in protein evolution.
Most eukaryotic proteins are multi-domain proteins that are created from fusions of genes, deletions and internal repetitions. An investigation of such evolutionary events requires a method to find the domain architecture from which each protein originates. Therefore, we defined a novel measure, domain distance, which is calculated as the number of domains that differ between two domain architectures. Using this measure the evolutionary events that distinguish a protein from its closest ancestor have been studied and it was found that indels are more common than internal repetition and that the exchange of a domain is rare. Indels and repetitions are common at both the N and C-terminals while they are rare between domains. The evolution of the majority of multi-domain proteins can be explained by the stepwise insertions of single domains, with the exception of repeats that sometimes are duplicated several domains in tandem. We show that domain distances agree with sequence similarity and semantic similarity based on gene ontology annotations. In addition, we demonstrate the use of the domain distance measure to build evolutionary trees. Finally, the evolution of multi-domain proteins is exemplified by a closer study of the evolution of two protein families, non-receptor tyrosine kinases and RhoGEFs.


Role of environmental factors in the pathogenesis of Crohn's disease: a critical review.
To review role of environmental factors in the pathogenesis of Crohn's disease. We systematically reviewed trials and systematic reviews using PubMed and Web of science databases. Here, we review the current information on the causative factors and mechanisms of CD, including smoking, exercise, diet, animal protein, breastfeeding, history of childhood infection and vaccination, oral contraceptives, and antibiotics of CD. We also highlight important knowledge gaps that need to be filled in order to advance the field of CD research. Epidemiological studies have indicated the significance of environmental factors in the disease behavior and outcome of Crohn's disease (CD). There are a few recognized environmental factors, such as cigarette smoking, exercise, dietary habits, and breastfeeding, which are associated with the pathogenesis of CD. These factors are hypothesized to change the epithelial barrier function, which disturbs both the innate and adaptive immune systems and the intestinal flora. However, the effect of several risk factors, such as appendectomy and pharmaceutical use, differs across several studies, indicating the need for more rigorous research. Furthermore, few studies have examined effective interventions based on environmental factors that can improve disease outcomes. Recent studies have indicated that the pathogenesis of CD is related to environmental and genetic factors. We review the current information on the causative factors and mechanisms of CD, including smoking, exercise, diet, animal protein, breastfeeding, history of childhood infection and vaccination, oral contraceptives, and antibiotics of CD. However, further studies are needed to understand knowledge gaps in the field of CD.


Unsuccessful percutaneous mechanical thrombectomy in fibrin-rich high-risk pulmonary thromboembolism.
We report a case of unsuccessful percutaneous mechanical thrombectomy in treatment of a high-risk pulmonary embolism (PE). Pulmonary thromboemboli are commonly expected as a homogenous mass, rich with red blood cell content, which respond well to percutaneous mechanical thrombectomy (PMT). Catheter-based approach or surgical embolectomy are two treatment options that are usually considered for treatment of high-risk PE when the thrombolytic therapy fails or it is contraindicated due to a patient's persisting hemodynamic compromise. Currently, selection criteria for PE treatment options are based mostly on the assessment of patient's history. The aim of this report is to highlight a possible treatment complication in PMT of structurally heterogeneous thrombotic mass due to PMT inadequacy. A 32 year-old male with polytrauma was admitted to an intensive care unit after a right-sided nephrectomy and evacuation of retroperitoneal hematoma. The patient initial haemostatic disorder was improved by administration of blood preparations, an anti-fibrinolytic agent and concentrates of fibrinogen. On the third day he presented sudden onset of hemodynamic instability and was incapable of standard CTA diagnostic procedure. Urgent and relevant investigations including transthoracic and transesophageal echocardiogram confirmed a high-risk PE. PMT was performed due to contraindications for systemic thrombolysis. Long-term PMT was attempted using aspiration with several devices. No major improvement was achieved in any of the treatments and the patient died. Autopsy confirmed a large heterogeneous thrombotic mass in the pulmonary trunk folding to the right main artery. Additional histological analysis revealed a high fibrin-rich content in the peripheral surroundings of the thrombus. In the case, it was confirmed that the outcome of PMT was directly influenced by mechanical and histological features of the thromboembolus in high-risk PE. Formation of a rather complex thromboembolus in high-risk PE favors surgical embolectomy as the only life-saving treatment option. Current diagnostic imaging techniques do not enable precise assessment of thrombi structure and are therefore unable to identify patients who might benefit from PMT or open surgical embolectomy. Surgical backup treatment should be considered if there are no contraindications in the event of a failed catheter intervention.


Impact of the COVID-19 pandemic on training conditions and education in oncologic disciplines: a survey-based analysis.
The COVID-19 pandemic has led to changes in global health care. Medical societies had to update guidelines and enhance new services such as video consultations. Cancer treatment had to be modified. The aim of this study is to ensure optimal care for cancer patients with the help of high-quality training even in times of crisis. We therefore conducted a nationwide survey of physicians in training in oncological disciplines during the pandemic to assess the impact on their education. The survey was sent to tumour centres, hospitals, specialist societies, and working and junior research groups and distributed via newsletters and homepages. Interim results and a call for participation were published as a poster (DEGRO) [26] and in the German Cancer Society (DKG) journal FORUM [42]. The survey contained 53 questions on conditions of education and training and on clinical and scientific work. Statistics were carried out with LimeSurvey and SPSS (IBM Corp., Armonk, NY, USA). Between February and November 2022, 450 participants answered the survey, with radio-oncologists being the largest group (28%). Most colleagues (63%) had access to digital training methods. Virtual sessions were rated as a good alternative, especially as multidisciplinary meetings (54%) as well as in-house and external training programs (48%, 47%). The time spent by training supervisors on education was rated as less than before the pandemic by 57%. Half of all participants perceived communication (54%), motivation (44%) and atmosphere (50%) in the team as bad. The participants felt strongly burdened by extra work (55%) and by a changed team atmosphere (49%). One third felt a change in the quality of training during the pandemic and rated it as negative (35%). According to 37% of the participants, this had little influence on their own quality of work. Additional subgroup analyses revealed significant differences in gender, specialty and education level. In order to improve oncology training in times of crisis, access to digital training options and meetings should be ensured. Participants wish for regular team meetings in person to enable good team spirit, compensation for overtime work and sufficient time for training supervisors for discussion and feedback.


In vitro follicle growth supports human oocyte meiotic maturation.
In vitro follicle growth is a potential approach to preserve fertility for young women who are facing a risk of premature ovarian failure (POF) caused by radiation or chemotherapy. Our two-step follicle culture strategy recapitulated the dynamic human follicle growth environment in vitro. Follicles developed from the preantral to antral stage, and, for the first time, produced meiotically competent metaphase II (MII) oocytes after in vitro maturation (IVM).


Larvicidal efficacy of the Citrus limetta peel extracts against Indian strains of Anopheles stephensi Liston and Aedes aegypti L.
The extracts from the peels of Citrus limetta were prepared using hexane and petroleum ether as the solvents. The larvicidal potential of each extract was assessed against dengue fever vector, Aedes aegypti, and malarial vector, Anopheles stephensi, by evaluating the toxicity effects on early fourth instars. Both the extracts were found effective against both the species. The bioassay with hexane extracts resulted in LC(50) values of 132.45 and 96.15 ppm against A. stephensi and A. aegypti, respectively; while the petroleum ether extracts from the C. limetta peels showed LC(50) values of 244.59 and 145.50 ppm, respectively. It revealed that the hexane extracts possessed 1.9-fold more larvicidal potential against A. stephensi and 1.5-fold more efficacy against A. aegypti as compared to the extracts obtained using petroleum ether as solvent. The data further revealed that the extracts were 1.4-1.7 times more effective against A. aegypti as compared to A. stephensi. The qualitative phytochemical study of the extracts showed the presence of terpenoids and flavonoids as the common phytochemical constituents in the extracts suggesting their possible role in the toxicity. Other constituents tested were not detected except alkaloids which were found to be present only in the petroleum ether extract. Further studies are needed to isolate and identify the active principles involved, their mode of action, formulated preparations for enhancing potency and stability, toxicity, and effects on non-target organisms and the environment. This could help in formulating efficient strategies for mosquito control.


ASNA1, an ATPase targeting tail-anchored proteins, regulates melanoma cell growth and sensitivity to cisplatin and arsenite.
ASNA1 is homologous to E. coli ArsA, a well characterized ATPase involved in efflux of arsenite and antimonite. Cells resistant to arsenite and antimonite are cross-resistant to the chemotherapeutic drug cisplatin. ASNA1 is also an essential ATPase for the insertion of tail-anchored proteins into ER membranes and a novel regulator of insulin secretion. The aim of this study was to determine if altered ASNA1 levels influenced growth and sensitivity to arsenite and cisplatin in human melanoma cells. Cultured melanoma T289 cells were transfected with plasmids containing sense or antisense ASNA1. Cells were exposed to cisplatin, arsenite and zinc. Cell growth and chemosensitivity were evaluated by the MTT assay and apoptosis by a TUNEL assay. ASNA1 expression was necessary for growth. T289 clones with decreased ASNA1 expression exhibited 51 +/- 5% longer doubling times than wildtype T289 (P = 0.0091). After exposure to cisplatin, ASNA1 downregulated cells displayed a significant increase in apoptosis. The cisplatin IC(50) in ASNA1 underexpressing cells was 41.7 +/- 1.8% compared to wildtype (P = 0.00097) and the arsenite IC(50) was 59.9 +/- 3.2% of wildtype IC(50) (P = 0.0067). Reduced ASNA1 expression is associated with significant inhibition of cell growth, increased apoptosis and increased sensitivity to cisplatin and arsenite.


Pre-transplant and longitudinal changes in faecal microbiome characteristics are associated with subsequent development of chronic graft-versus-host disease.
The role of the gastrointestinal microbiome in predisposing to chronic graft-versus-host disease (cGVHD), an immune-mediated haematopoietic cell transplant (HCT) complication, is not well defined. We examined the relationship of the host faecal microbiome with subsequent cGVHD development by analysing baseline stool samples as well as post-HCT changes in microbiome composition and metabolite pathway analyses. We analysed pre-transplant baseline samples from 11 patients who subsequently developed cGVHD compared to 13 controls who did not develop acute GVHD or cGVHD at any time. We found a significant differential abundance of multiple taxa at baseline between cGVHD versus controls, including the Actinobacteria phylum and Clostridium genus. A subgroup analysis of longitudinal samples within each patient revealed a greater loss of alpha diversity from baseline to post-engraftment in patients who subsequently developed cGVHD. Metabolic pathways analysis revealed that two pathways associated with short-chain fatty acid metabolism were enriched in cGVHD patient microbiomes: β-oxidation and acyl-CoA synthesis, and γ-aminobutyrate shunt. In contrast, a tryptophan catabolism pathway was enriched in controls. Our findings show a distinct pattern of baseline microbiome and metabolic capacity that may play a role in modulating alloreactivity in patients developing cGVHD. These findings support the therapeutic potential of microbiome manipulation for cGVHD prevention.


H. pylori infection increases levels of exhaled nitrate.
Helicobacter pylori infection is one of the most common chronic bacterial infections worldwide. Despite the existence of a breath test for the diagnosis of H. pylori infection, no study has described the composition of volatile compounds, especially the levels of nitrate, in the exhaled air of patients with H. pylori infection. The volatile compounds in the exhaled air of 14 patients suffering from H. pylori gastritis and 11 controls were analyzed using proton transfer reaction-mass spectrometry. Gastric biopsy was used to establish diagnosis of current H. pylori infection. Comparing mass spectra between groups, Mass 28 (hydrogen cyanide, HCN) and Mass 64 (hydrogen nitrate, H2NO3) were found to be significantly elevated in patients with H. pylori infection. The main result of the present study is that in H. pylori-infected patients, levels of exhaled hydrogen nitrate and hydrogen cyanide are found to be significantly elevated. However, further studies are necessary to find out whether the differences in the detected mass spectrum are specific enough to differentiate patients with H. pylori gastritis from healthy controls.


Spatiotemporally dissociable neural signatures for generating and updating expectation over time in children: A High Density-ERP study.
Temporal orienting (TO) is the allocation of attentional resources in time based on the a priori generation of temporal expectancy of relevant stimuli as well as the a posteriori updating of this expectancy as a function of both sensory-based evidence and elapsing time. These processes rely on dissociable cognitive mechanisms and neural networks. Yet, although there is evidence that TO may be a core mechanism for cognitive functioning in childhood, the developmental spatiotemporal neural dynamics of this mechanism are little understood. In this study we employed a combined approach based on the application of distributed source reconstruction on a high spatial resolution ERP data array obtained from eighteen 8- to 12-year-old children completing a TO paradigm in which both the cue (Temporal vs. Neutral) and the SOA (Short vs. Long) were manipulated. Results show both cue (N1) and SOA (CNV, Omission Detection Potential and Anterior Anticipatory Index) ERP effects, which were associated with expectancy generation and updating, respectively. Only cue-related effects were correlated with age, as revealed by a reduction of the N1 delta effect with increasing age. Our data suggest that the neural correlates underlying TO are already established at least from 8 to 12 years of age.


Outcomes of right lobe donors with BMI≥30 for living donor liver transplantation.
Donor BMI above 30 is generally considered contraindication for donor hepatectomy. We compared the donor outcomes based on BMI threshold and weight loss. All potential donors were identified and data were collected retrospectively. Steatosis was assessed based on liver-spleen Hounsfield unit difference and absolute liver intensity values. We compared BMI≥30 (n = 53) and BMI < 30 (n = 64) donor outcomes. Donors with weight loss (WL) prior to surgery were also analyzed separately. Complications were graded by Clavien-Dindo classification. All donors underwent open right donor hepatectomy. There was no difference between BMI≥30 and < 30 groups except female predominance in BMI≥30 group (P = .006). Both groups had similar rates of complication rates in all categories, similar remnant volume, operative time, length of stay and similar postoperative liver function recovery (all P > .05). On the other hand, donors with WL were more commonly male, had smaller graft size, and higher biliary complications rates compared to no-WL donors (all P < .05). Multivariate binary logistics regression analysis revealed no association between BMI or WL and outcomes. We demonstrate that donors with BMI≥30 have similar outcomes compared to BMI < 30 donors with our defined selection criterion, therefore BMI≥30 is not an absolute contraindication to donate right liver, provided that there is no significant steatosis and remnant liver is satisfactory. For potential overweight donors, WL down to BMI < 30 is a reasonable target. Higher biliary complication rates after WL should be investigated further.


Expression of a MORN repeat protein from Euplotes octocarinatus requires a +1 programmed ribosomal frameshifting.
Analysis of transcriptome revealed that a membrane occupation and recognition nexus (MORN) repeat protein-encoding gene of Euplotes octocarinatus (Eo-morn-9-31) was a candidate for programmed +1 ribosomal frameshifting (+1 PRF). In this study, a dual-luciferase assay was performed to detect its expression. The result showed that the MORN repeat protein (Eo-MORN-9-31) could be produced by the +1 PRF event during the process of translation in yeast and the frameshifting efficiency was about 4-5%. We further confirmed its reality by western blot and mass spectrometry. This study provided experimental evidence indicating that the expression of the Eo-MORN-9-31 of E. octocarinatus required the +1 PRF.


Bioinformatic Prediction of Novel Signaling Pathways of Apoptosis-inducing Factor, Mitochondrion-associated 3 (AIFM3) and Their Roles in Metastasis of Cholangiocarcinoma Cells.
We previously demonstrated that a mitochondrial protein, apoptosis-inducing factor, mitochondrion-associated 3 (AIFM3) is over-expressed in cholangiocarcinoma (CCA) and its serum levels can be a prognostic biomarker for CCA. To elucidate the functional roles of AIFM3 in CCA progression, we aimed to determine the signaling pathways of AIFM3 in CCA. AIFM3 gene in CCA cells was silenced and AIFM3-related proteins were identified using mass spectrometry and bioinformatics tools. The relationships between AIFM3 and 441 related proteins were explored. To validate the functions of AIFM3, transwell migration/invasion assays were used. Bioinformatic analyses predicted that AIFM3 interacts with formin-like protein 3 (FMNL3) and is involved in tumor cell motilities. Online database analysis revealed higher AIFM3 mRNA expression levels in CCA, particularly with lymph node metastasis. After AIFM3 gene silencing, CCA cell migration/invasion was significantly decreased (p<0.001). Furthermore, AIFM3 expression levels were significantly associated with lymph node metastasis (p=0.0009) and shorter survival time (p=0.020). The AIFM3 signaling pathway is mediated via FMNL3 and involved in metastasis, suggesting that AIFM3 might be a molecular target to prevent CCA metastasis.


Correction to: Effects of workload, work complexity, and repeated alerts on alert fatigue in a clinical decision support system.
Following publication of the original article [1], the authors reported that the article erroneously stated that Dr. Ancker was affiliated with the Tehran University of Medical Sciences. Dr. Ancker is not affiliated with that institution.


Development of an online calculator for the prediction of seizure freedom following pediatric hemispherectomy using the Hemispherectomy Outcome Prediction Scale (HOPS).
Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy. Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/). The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%. Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.


Carbonic anhydrase inhibitors: inhibition of the transmembrane isozyme XIV with sulfonamides.
The inhibition of the last human carbonic anhydrase (CA, EC 18.104.22.168) isozyme (hCA XIV) discovered has been investigated with a series of sulfonamides, including some clinically used derivatives (acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, benzolamide, and zonisamide), as well as the sulfamate antiepileptic drug topiramate. The full-length hCA XIV is an enzyme showing a medium-low catalytic activity, quite similar to that of hCA XII, with the following kinetic parameters at 20 degrees C and pH 7.5, for the CO2 hydration reaction: k(cat) = 3.12 x 10(5) s(-1) and k(cat)/K(M) = 3.9 x 10(7) M(-1) s(-1). All types of activities have been detected for the investigated compounds, with several micromolar inhibitors, including zonisamide, topiramate, and simple sulfanilamide derivatives (K(I)-s in the range of 1.46-6.50 microM). In addition, topiramate and zonisamide were observed to behave as weak hCA XII inhibitors, while zonisamide was an effective hCA IX inhibitor (K(I) of 5.1 nM). Some benzene-1,3-disulfonamide derivatives or simple five-membered heteroaromatic sulfonamides showed K(I)-s in the range of 180-680 nM against hCA XIV, whereas the most effective of such inhibitors, including 3-chloro-/bromo-sulfanilamide, benzolamide-like, ethoxzolamide-like, and acetazolamide/methazolamide-like derivatives, showed inhibition constant in the range of 13-48 nM. The best hCA XIV inhibitor was aminobenzolamide (K(I) of 13 nM), but no CA XIV-selective derivatives were evidenced. There are important differences of affinity of these sulfonamides/sulfamates for the three transmembrane CA isozymes, with CA XII showing the highest affinity, followed by CA IX, whereas CA XIV usually showed the lowest affinity for these inhibitors.