Categorization-based stranger avoidance does not explain the uncanny valley effect.
The uncanny valley hypothesis predicts that an entity appearing almost human risks eliciting cold, eerie feelings in viewers. Categorization-based stranger avoidance theory identifies the cause of this feeling as categorizing the entity into a novel category. This explanation is doubtful because stranger is not a novel category in adults; infants do not avoid strangers while the category stranger remains novel; infants old enough to fear strangers prefer photographs of strangers to those more closely resembling a familiar person; and the uncanny valley's characteristic eeriness is seldom felt when meeting strangers. We repeated our original experiment with a more realistic 3D computer model and found no support for categorization-based stranger avoidance theory. By contrast, realism inconsistency theory explains cold, eerie feelings elicited by transitions between instances of two different, mutually exclusive categories, given that at least one category is anthropomorphic: Cold, eerie feelings are caused by prediction error from perceiving some features as features of the first category and other features as features of the second category. In principle, realism inconsistency theory can explain not only negative evaluations of transitions between real and computer modeled humans but also between different vertebrate species.


Patients with emphysema: quantitative CT analysis before and after lung volume reduction surgery. Work in progress.
To quantitatively assess the morphologic changes in the lungs after lung volume reduction surgery and determine whether changes at quantitative computed tomography (CT) reflect changes in lung function. In 10 patients, chest CT images were obtained at full inspiration and expiration before and after surgery. A semiautomated segmentation method was developed to isolate the lung regions and calculate the lung volumes and frequency distribution of attenuation values. The changes in lung volume and attenuation after surgery were compared with clinical findings, and an exploratory evaluation of outcome predictors was conducted. Semiautomated segmentation and quantitative analysis compared favorably with manual techniques, and there was good correlation between the emphysema indexes and percentage predicted forced expiratory volume in 1 second, forced expiratory volume in 1 second/forced vital capacity, and diffusing capacity. The emphysema index decreased from 60% to 38% at inspiration and from 60% to 27% at expiration after surgery. The average CT lung volume decreased from 7.5 to 5.6 L at inspiration (25%) and from 6.4 to 3.8 L (41%) at expiration after surgery and correlated well with measurements at plethysmography. Substantial decreases in the lung volumes and emphysema index, increased airflow, possible reexpansion of some remaining lung, and the relation between preoperative quantitative CT indexes and clinical outcome suggest a multifactorial mechanism for improvement seen after surgery.


Amount and Socio-Ecological Correlates of Exercise in Men and Women at Cardiac Rehabilitation Completion.
The aim of the study was to describe (1) the amount of physical activity (PA) in cardiac rehabilitation (CR) graduates by sex, and (2) the correlates of their PA. Secondary analysis of baseline data from a randomized trial was undertaken. Graduates were recruited from three CR programs. Participants completed a questionnaire, which assessed constructs from the socio-ecological model (i.e., individual-level, social- and physical-environmental levels). Physical activity was measured objectively using an ActiGraph GT3X accelerometer. Multilevel modeling was performed. Two hundred fifty-five patients consented, of which 200 (78.4%) completed the survey and provided valid accelerometer data. Participants self-reported engaging in a mean ± standard deviation of 184.51 ± 129.10 min of moderate-to-vigorous-intensity PA (MVPA) per week (with men engaging in more than women, P < 0.05). Accelerometer data revealed participants engaged in 169.65 ± 136.49 mins of MVPA per week, with 43 (25.1%) meeting recommendations. In the mixed models, the socio-ecological correlate significantly related to greater self-reported MVPA was self-regulation (P = 0.01); the correlate of accelerometer-derived MVPA was neighborhood aesthetics (P = 0.02). Approximately one-quarter of CR program completers are achieving MVPA recommendations, although two-thirds perceive they are. The CR programs should exploit accelerometry and promote self-regulation skills, namely, self-monitoring, goal-setting, positive reinforcement, time management, and relapse prevention. Patients should be encouraged to exercise in pleasing locations.


Synchytrium solstitiale sp. nov. causing a false rust on Centaurea solstitialis in France.
A new species of Synchytrium, S. solstitiale, infecting leaves of Centaurea solstitialis in France, is described and illustrated. Synchytrium solstitiale causes development of orange to red galls on the leaves and petioles of living plants. It differs microscopically from all previously described species of the genus mainly in having larger sporangia and zoospores and resting spores that are formed in succession without an evanescent prosoral stage.


RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL.
RIPK3 and its substrate MLKL are essential for necroptosis, a lytic cell death proposed to cause inflammation via the release of intracellular molecules. Whether and how RIPK3 might drive inflammation in a manner independent of MLKL and cell lysis remains unclear. Here we show that following LPS treatment, or LPS-induced necroptosis, the TLR adaptor protein TRIF and inhibitor of apoptosis proteins (IAPs: X-linked IAP, cellular IAP1 and IAP2) regulate RIPK3 and MLKL ubiquitylation. Hence, when IAPs are absent, LPS triggers RIPK3 to activate caspase-8, promoting apoptosis and NLRP3-caspase-1 activation, independent of RIPK3 kinase activity and MLKL. In contrast, in the absence of both IAPs and caspase-8, RIPK3 kinase activity and MLKL are essential for TLR-induced NLRP3 activation. Consistent with in vitro experiments, interleukin-1 (IL-1)-dependent autoantibody-mediated arthritis is exacerbated in mice lacking IAPs, and is reduced by deletion of RIPK3, but not MLKL. Therefore RIPK3 can promote NLRP3 inflammasome and IL-1β inflammatory responses independent of MLKL and necroptotic cell death.


Auditory epithelial migration. II: Morphological evidence for auditory epidermal cell migration in rat.
Morphology of the tympanic membrane (TM) and external auditory canal (EAC) was studied in healthy, intact rat ears. TM-perforated ears (3 days after making the perforation) and TM-perforation-healed ears (14, 28 and 42 days after making the perforation). In intact ears, the epidermis in the annular region of the EAC displayed a characteristic appearance with cytoplasmic protrusions. We termed these protrusions as "finger-like projections". In contrast to the rat, the annular region of the EAC in the guinea-pig did not show "finger-like projections". Following a perforation in the centre of the anterior or the posterior quadrant of the pars tensa in rats the "finger-like projections" disappeared from the annular region on the perforated side of the EAC, while the projections remained on the malleus side of the perforation edge. In perforation-healed ears analysed 42 days after the perforation, the "finger-like projections" had recurred in the annular region on the perforated side of the EAC. The "finger-like projections" are likely to express maturation (keratinization) and desquamation of epidermal cells in the pars tensa and also could constitute morphological evidence of their migration on the TM.


[Studies on absorption and transportation of coumarins in Angelica dahurica 'Yubaizhi' across human intestinal epithelial by using human Caco-2 cell monolayers].
The absorption is the key to the resulted efficacy of orally administered drugs and the small intestine is the main site to absorb the orally administered drug. In this paper, internationally recognized human colon adenocarcinoma cell line(Caco-2) monola-yer model which can simulate small intestinal epithelial cell was used to comparatively study the absorption and transportation diffe-rences of total coumarins and main individual coumarin in Angelica dahurica 'Yubaizhi' by separately using 6-and 12-well plates. It was found that apparent permeability coefficient(P_(app)) values of oxypeucedanin hydrate, byakangelicin and phellopterin were at the quantitative degree of 1 × 10~(-5) cm·s~(-1) when the individual administration was conducted independently, indicating that they were well-absorbed compounds. P_(app) ratio of their bi-directional transportation was close to 1, indicating that they can be absorbed across Caco-2 monolayer by passive diffusion mechanism without carrier mediation during the transportation. The similar trend of transportation was also observed for imperatorin, isoimperatorin and bergapten. The P_(app) values of oxypeucedanin hydrate, byakangelicin and bergapten were at quantitative degree of 1 × 10~(-5) cm·s~(-1) when the administration of total coumarins in Angelica dahurica 'Yubaizhi' was conducted, indicating that they were well-absorbed compounds. The results were consistent with those of independent administration of individual coumarins. Whereas, the P_(app) values of imperatorin, phellopterin and isoimperatorin in the total coumarins decreased, indicating that the interaction between compounds may exist although the P_(app) value ratio of bi-directional transportation was between 0.5 and 1.5. The results laid the foundation for intestinal absorption study of Angelica dahurica 'Yubaizhi' coumarins in compound Chinese medicine.


Time management: Improving the timing of post-prostatectomy radiotherapy, clinical trials, and knowledge translation.
Management of prostate cancer after surgery is controversial. Past studies on adjuvant radiotherapy (aRT) for higher-risk features have had conflicting results. Through the collaborative conversations of the global radiation oncology Twitter-based journal club (#RadOnc #JC), we explored this complex topic to share recent advances, better understand what the global radiation oncology community felt was important and inspire next steps. We selected the recent publication of a landmark international randomized controlled trial (RCT) comparing immediate and salvage radiotherapy for prostate cancer, RADICALS-RT, for discussion over the weekend of January 16 to 17, 2021. Coordination included open access to the article and an asynchronous portion to decrease barriers to participation, cooperation of study authors (CP, MS) who participated to share deeper insights including a live hour, and curation of related resources and tweet content through a blog post and Wakelet journal club summary. Our conversations created 2,370,104 impressions over 599 tweets with 51 participants spanning 11 countries and 5 continents. A quarter of the participants were from the US (13/51) followed by 10% from the UK (5/51). Clinical or Radiation Oncologists comprised 59% of active participants (16/27) with 62% (18/29) reporting giving aRT within the last 5 years. Discussion was interdisciplinary with three urologists (11%), three trainees (11%), and two physiotherapists (7%). Four months after the journal club its article Altmetric score had increased by 7% (214 to 229). Thematic analysis of tweet content suggested participants wanted clarification on definitions of adjuvant (aRT) and salvage radiotherapy (sRT) including indications, timing, and decision-making tools including guidelines; more interdisciplinary and cross-sectoral collaboration including with patients for study design including survivorship and meaningful outcomes; more effective knowledge translation including faster clinical trials; and more data including mature results of current trials, particular high-risk features (Gleason Group 4+, pT4b+, and margin-positive disease), implications of newer technologies such as PSMA-PET and genomic classifiers, and better explanations for practice pattern variations including underutilization of radiotherapy. This was further explored in the context of relevant literature. Together, this global collaborative review on the postoperative management of prostate cancer suggested a stronger signal for the uptake of early salvage radiation treatment with careful PSA monitoring, more sensitive PSA triggers, and expected access to radiotherapy. Questions still remain on potential exceptions and barriers to use. These require better decision-making tools for all practice settings, consideration of newer technologies, more pragmatic trials, and better use of social media for knowledge translation.


Reduction of Allergenic Potential in Bread Wheat RNAi Transgenic Lines Silenced for CM3, CM16 and 0.28 ATI Genes.
Although wheat is used worldwide as a staple food, it can give rise to adverse reactions, for which the triggering factors have not been identified yet. These reactions can be caused mainly by kernel proteins, both gluten and non-gluten proteins. Among these latter proteins, α-amylase/trypsin inhibitors (ATI) are involved in baker's asthma and realistically in Non Celiac Wheat Sensitivity (NCWS). In this paper, we report characterization of three transgenic lines obtained from the bread wheat cultivar Bobwhite silenced by RNAi in the three ATI genes CM3, CM16 and 0.28. We have obtained transgenic lines showing an effective decrease in the activity of target genes that, although showing a higher trypsin inhibition as a pleiotropic effect, generate a lower reaction when tested with sera of patients allergic to wheat, accounting for the important role of the three target proteins in wheat allergies. Finally, these lines show unintended differences in high molecular weight glutenin subunits (HMW-GS) accumulation, involved in technological performances, but do not show differences in terms of yield. The development of new genotypes accumulating a lower amount of proteins potentially or effectively involved in allergies to wheat and NCWS, not only offers the possibility to use them as a basis for the production of varieties with a lower impact on adverse reaction, but also to test if these proteins are actually implicated in those pathologies for which the triggering factor has not been established yet.


Molecularly targeted therapies for colorectal cancer: Strategies for implementing translational research in clinical trials.
Few breakthroughs in preclinical research have translated into meaningful benefits, either in clinical terms or quality of life, for patients with advanced colorectal cancer, despite important preclinical discoveries regarding aberrant biological pathways associated with disease development and progression. The many reasons for the slow progress are diverse, ranging from the failure to codevelop biomarkers and targeted therapies, the regulatory burdens imposed on academic investigators, and the failure to collect serial tumor biopsies during clinical trials. This review discusses promising translational research that could help reduce the disparity between preclinical discovery and patient benefit, and advocate the concentration of efforts and resources on the most promising therapeutic targets in colorectal cancer, such as EGFR, VEGF and Fcγ receptor.


Lower limb blocks for children. Lateral cutaneous and femoral nerve blocks for postoperative pain relief in paediatric practice.
Femoral and lateral cutaneous nerve of the thigh blocks have been performed in a group of 50 children; the method has not previously been described in paediatric practice. The technique was judged to have been successful in 48 (96%) of the children. There were no early or late complications. It is concluded that these blocks are easy to perform, even in small children and infants, and that they can produce reliable postoperative analgesia for a variety of orthopaedic and plastic procedures.


Four-angle saturation transfer (FAST) method for measuring creatine kinase reaction rates in vivo.
A new fast method of measuring kinetic reaction rates for two-site chemical exchange is described. The method employs saturation transfer magnetic resonance spectroscopy (MRS) and acquisition of only four spectra under partially saturated, high signal-to-noise ratio (SNR) conditions. In two acquisitions one of the exchanging species is saturated; the other two employ a control saturation. Each pair of acquisitions is applied with two different flip angles, and the equilibrium magnetization, relaxation times, and reaction rates are calculated therefrom. This four-angle saturation transfer (FAST) method is validated theoretically using the Bloch equations modified for two-state chemical exchange. Potential errors in the rate measurements due to the effects of exchange are evaluated for creatine kinase (CK) metabolism modeled for skeletal and heart muscle, and are found to be < 5% for forward CK flux rates of 0.05 < or = k(f) < or = 1.0 s(-1), and up to a 90% depletion of phosphocreatine (PCr). The effect of too much or too little saturating irradiation on FAST appears to be comparable to that of the conventional saturation transfer method, although the relative performance deteriorates when spillover irradiation cuts the PCr signal by 50% or more. "FASTer" and " FASTest" protocols are introduced for dynamic CK studies wherein [PCr] and/or k(f) changes. These protocols permit the omission of one or two of the four acquisitions in repeat experiments, and the missing information is recreated from initial data via a new iterative algorithm. The FAST method is validated empirically in phosphorus ((31)P) MRS studies of human calf muscle at 1.5 T. FAST measurements of 10 normal volunteers yielded the same CK reaction rates measured by the conventional method (0.29 +/- 0.06 s(-1)) in the same subjects, but an average of seven times faster. Application of the FASTer algorithm to these data correctly restored missing information within seven iterations. Finally, the FAST method was combined with 1D spatially localized (31)P MRS in a study of six volunteers, yielding the same k(f) values independent of depth, in total acquisition times of 17-39 min. These timesaving FAST methods are enabling because they permit localized measurements of metabolic flux, which were previously impractical due to intolerably long scan times.


Multidisciplinary team training to enhance family communication in the ICU.
Current guidelines from the U.S. Society for Critical Care Medicine state that training in "good communication skills...should become a standard component of medical education and ... available for all ICU caregivers". We sought to train multidisciplinary teams of ICU caregivers in communicating with the families of critically ill patients to improve staff confidence in communicating with families, as well as family satisfaction with their experiences in the ICU. Pre- and postintervention design. Community hospital medical and surgical ICUs. All patients admitted to ICU during the two time periods. Ninety-eight caregivers in multidisciplinary teams of five to eight individuals trained in a standardized approach to communicating with families of ICU patients using the Setup, Perception, Invitation, Knowledge, Emotions, Strategy (or Subsequent) (SPIKES) protocol followed by participation in a simulated family conference. Staff confidence in communicating with family members of critically ill patients was measured immediately before and 6-8 weeks after training sessions using a validated tool. Family satisfaction using seven items measuring effectiveness of communication from the Family Satisfaction in the ICU (24) tool in surveys received from family members of 121 patients admitted to the ICU before and 121 patients admitted to the ICU after trainings was completed. Using 46 matched pre- and postsurveys, staff confidence in communicating with family members of critically ill patients increased significantly (p < 0.001) in each of 21 separate measures. Family satisfaction with communication showed significant (p < 0.05 or better) improvement in three of seven individual items compared with those same items pretraining. There was no decline in any individual item. A simple intervention resulted in improvement in staff confidence, as well as in multiple measures of family satisfaction with communication. This intervention is easily reproduced.


[Development of sociopsychological adaptation of schoolchildren and vocational school pupils].
The purpose of this study was to comparatively analyze the influence of family factors on social and psychological adaptation and achievement motivation in pupils from general education schools and in their coevals from vocational educational schools (VES). An experimental study was conducted in 10th-form pupils from a number of Moscow schools and persons of the same age who were one-year course pupils from a Moscow VES. A total of 242 pupils, including 130 schoolchildren and 112 one-year course pupils from the VES, were examined. The social and psychological adaptation questionnaire developed by K. Rodgers and R. Diamond was used to estimate achievement motivation by the Mehrabian test. The performed study confirmed the negative impact of poor family relations on pupils' sociological and psychological adaptation independently of the type of a general educational establishment. The high maternal educational level had a good effect on the adaptability of schoolchildren, that of boys in particular, whereas the paternal educational status is of the same value to VES pupils. Family relations and maternal and paternal education levels significantly affect the formation of achievement motive in pupils and their social and psychological adaptation as a whole.


Concealment of drugs in food and beverages in nursing homes: cross sectional study.
To examine the practice of concealing drugs in patients' foodstuff in nursing homes. Cross sectional study with data collected by structured interview. All five health regions in Norway. Professional carers of 1362 patients in 160 regular nursing home units and 564 patients in 90 special care units for people with dementia. Frequency of concealment of drugs; who decided to conceal the drugs; how this practice was documented in the patients' records; and what types of drugs were given this way. 11% of the patients in regular nursing home units and 17% of the patients in special care units for people with dementia received drugs mixed in their food or beverages at least once during seven days. In 95% of cases, drugs were routinely mixed in the food or beverages. The practice was documented in patients' records in 40% (96/241) of cases. The covert administration of drugs was more often documented when the physician took the decision to hide the drugs in the patient's foodstuff (57%; 27/47) than when the person who made the decision was unknown or not recorded (23%; 7/30). Patients who got drugs covertly more often received antiepileptics, antipsychotics, and anxiolytics compared with patients who were given their drugs openly. The covert administration of drugs is common in Norwegian nursing homes. Routines for such practice are arbitrary, and the practice is poorly documented in the patients' records.


Cardiovascular disease in a nationwide population of Danish women with polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is associated with obesity and low grade inflammation and the risk for cardiovascular disease (CVD) could be increased in PCOS. National register-based study including women with PCOS and no previous diagnosis of CVD, hypertension, or dyslipidemia. PCOS Denmark (N = 18,112) included women with PCOS in the Danish National Patient Register. PCOS Odense University Hospital (OUH, N = 1165) was an embedded cohort including premenopausal women with PCOS and clinical and biochemical examination. Three age-matched controls were included per patient in PCOS Denmark (N = 52,769). The main study outcome was CVD events including hypertension and dyslipidemia defined according to nationwide in- and outpatient hospital contact diagnosis codes and/or inferred from filled medicine prescriptions. The age at inclusion was median (quartiles) 29 (23-35) years and follow up was 11.1 (6.9-16.0) years. The Hazard ratio (95% CI) for development of CVD in PCOS Denmark was 1.7 (1.7; 1.8) (P < 0.001) and the total event rate of CVD was 22.6 per 1000 patient years in PCOS Denmark vs. 13.2 per 1000 patient years in controls (P < 0.001). The median age at diagnosis of CVD was 35 (28-42) years in PCOS Denmark vs. 36 (30-43) years in controls (P < 0.001). Obesity, diabetes, and infertility, and previous use of oral contraceptives were associated with increased risk of development of CVD in PCOS Denmark (P < 0.001). Women in PCOS OUH resembled women in PCOS Denmark regarding risk of CVD. Age, BMI, blood pressure, lipid status, and glycemic status predicted development of CVD in PCOS OUH. The event rate of CVD including hypertension and dyslipidemia was higher in PCOS compared to controls. The risk of developing CVD must be considered even in young women with PCOS.


Magnesium and the acute physician.
Magnesium deficiency, and to a lesser extent magnesium excess, is commonly encountered in patients admitted to the Acute Medical Unit. It is important that acute physicians are able to identify those at risk of these states and initiate appropriate investigation and treatment. This article aims to provide the reader with a sound understanding of magnesium physiology and its effect at a cellular level. The causes, symptoms and treatment of magnesium disorders are discussed along with a review of evidence regarding the therapeutic use of magnesium.


Parents' preferences for the organisation of long-term follow-up of childhood cancer survivors.
Parents take an important role in follow-up of young cancer survivors. We aimed to investigate (1) parents' preferences for organisation of follow-up (including content, specialists involved and models of care), and (2) parents' and children's characteristics predicting preference for generalist vs. specialist-led follow-up. We sent a questionnaire to parents of childhood cancer survivors aged 11-17 years. We assessed on a 4-point Likert scale (1-4), parents' preferences for organisation of long-term follow-up. Proposed models were: telephone/questionnaire, general practitioner (GP) (both categorised as generalist for regression analysis); and paediatric oncologist, medical oncologist or multidisciplinary team (MDT) (categorised as specialists). Of 284 contacted parents, 189 responded (67%). Parents welcomed if visits included checking for cancer recurrence (mean = 3.89), late effects screening (mean = 3.79), taking patients seriously (mean = 3.86) and competent staff (mean = 3.85). The preferred specialists were paediatric oncologists (mean = 3.73). Parents valued the paediatric oncologist model of care (mean = 3.49) and the MDT model (mean = 3.14) highest. Parents of children not attending clinic-based follow-up (OR = 2.97, p = .009) and those visiting a generalist (OR = 4.23, p = .007) favoured the generalist-led model. Many parents preferred a clinic-based model of follow-up by paediatric oncologists or a MDT. However, parents also valued the follow-up care model according to which their child is followed up.


Predictors of HIV enacted stigma among Chilean women.
To investigate if socio-demographic factors, religiosity, HIV-related knowledge, Marianismo, history of having been tested for HIV, knowing someone who died of AIDS and HIV risk perception were predictive factors to HIV enacted stigma predictors among Chilean women. HIV infection is the number one cause of death among women during their reproductive years. In Chile, studies with people living with HIV demonstrate the existence of HIV-related stigma. However, limited evidence is available about the underlying causes of HIV enacted stigma that results in stigmatisation and discrimination. The current cross-sectional study is a secondary analysis of data collected to assess the impact of an HIV prevention intervention (Mano a Mano-Mujer) designed for Chilean women. A quasi-experimental design was used in the original study. This study was conducted in two communities in Santiago, Chile. The sample for this study consisted of 496 Chileans between ages 18-49. Descriptive statistics and multiple regression were used for the analysis. Participants in the study reported high levels (77·8%) of HIV enacted stigma. Higher levels of HIV-related knowledge were associated with lower levels of HIV enacted stigma. Women with higher education had lower levels of HIV enacted stigma than women with elementary education. In addition, greater levels of marianismo (cultural belief that women should be passive, faithful, and devoted to family) were associated with higher HIV enacted stigma scores. The findings reflected the presence of HIV enacted stigma among Chilean women. Identifying the significant predictors of HIV enacted stigma can help the nursing community to design HIV prevention interventions that include the reduction in HIV enacted stigma. HIV evidence-based prevention interventions should incorporate contents related to stigma to contribute to prevent HIV enacted stigma at individual and community levels in accordance with the bioecological model. The results of this study could serve to develop HIV prevention interventions that target the reduction in HIV enacted stigma.


An Individualized Prognostic Signature for Clinically Predicting the Survival of Patients With Bladder Cancer.
Background: The tumor immune microenvironment (TIME) plays an important role in the development and prognosis of bladder cancer. It is essential to conduct a risk model to explore the prognostic value of the immunologic genes and establish an individualized prognostic signature for predicting the survival of patients with bladder cancer. Method: The differentially expressed immunologic genes (DEGs) are identified in The Cancer Genome Atlas (TCGA). The nonnegative matrix factorization (NMF) was used to stratify the DEGs in TCGA. We used the least absolute shrinkage and selection operator (LASSO) Cox regression and univariate Cox analysis to establish a prognostic risk model. A nomogram was used to establish an individualized prognostic signature for predicting survival. The potential pathways underlying the model were explored. Results: A total of 1,018 DEGs were screened. All samples were divided into two clusters (C1 and C2) by NMF with different immune cell infiltration, and the C2 subtype had poor prognosis. We constructed a 15-gene prognostic risk model from TCGA cohort. The patients from the high-risk group had a poor overall survival rate compared with the low-risk group. Time-dependent ROC curves demonstrated good predictive ability of the signature (0.827, 0.802, and 0.812 for 1-, 3-, and 5-year survival, respectively). Univariate and multivariate Cox regression analyses showed that the immunologic prognostic risk model was an independent factor. The decision curve demonstrated a relatively good performance of the risk model and individualized prognostic signature, showing the best net benefit for 1-, 3-, and 5-year OS. Gene aggregation analysis showed that the high-risk group was mainly concentrated in tumorigenesis and migration and immune signaling pathways. Conclusion: We established a risk model and an individualized prognostic signature, and these may be useful biomarkers for prognostic prediction of patients with bladder cancer.


A Phase III Study to Compare the Efficacy and Safety of Paclitaxel Versus Irinotecan in Patients with Metastatic or Recurrent Gastric Cancer Who Failed in First-line Therapy (KCSG ST10-01).
Irinotecan could not be proven noninferior to paclitaxel as a second-line treatment for patients with metastatic or recurrent gastric cancer.The failure to demonstrate noninferiority may have been a result of insufficient patient enrollment.Both agents were tolerable but showed different toxicity profiles. This phase III study compared the efficacy and safety of paclitaxel versus irinotecan in patients with metastatic or recurrent gastric cancer (MRGC) who had experienced disease progression following first-line chemotherapy. Patients were randomized to receive either paclitaxel (70 mg/m2; days 1, 8, 15, every 4 weeks) or irinotecan (150 mg/m2 every other week). The primary endpoint was progression-free survival (PFS). This study was stopped early due to low accrual rate. A total of 112 patients were enrolled; 54 were allocated to paclitaxel and 58 to irinotecan. Median PFS for the paclitaxel and irinotecan groups was 3.5 and 2.1 months, respectively (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.86-1.88; p = .234). Noninferiority of irinotecan to paclitaxel was not proved because the upper boundary of the 95% CI (1.88) exceeded the predefined upper margin of noninferiority (1.32). Median overall survival (OS) was 8.6 months in the paclitaxel group and 7.0 months in the irinotecan group (HR, 1.39; 95% CI, 0.91-2.11; p = .126). Among toxicities greater than or equal to grade 3, neutropenia (11.5%) was the most common, followed by peripheral neuropathy (7.7%) in the paclitaxel group, and neutropenia (34.5%) followed by nausea, vomiting, and anemia (8.6%, respectively) in the irinotecan group. Although paclitaxel showed numerically longer PFS and OS compared with irinotecan, this was statistically insignificant. Both irinotecan and paclitaxel are valid second-line treatment options in MRGC.


Automatic planning of head and neck treatment plans.
Treatment planning is time-consuming and the outcome depends on the person performing the optimization. A system that automates treatment planning could potentially reduce the manual time required for optimization and could also provide a method to reduce the variation between persons performing radiation dose planning (dosimetrist) and potentially improve the overall plan quality. This study evaluates the performance of the Auto-Planning module that has recently become clinically available in the Pinnacle3 radiation therapy treatment planning system. Twenty-six clinically delivered head and neck treatment plans were reoptimized with the Auto-Planning module. Comparison of the two types of treatment plans were performed using DVH metrics and a blinded clinical evaluation by two senior radiation oncologists using a scale from one to six. Both evaluations investigated dose coverage of target and dose to healthy tissues. Auto-Planning was able to produce clinically acceptable treatment plans in all 26 cases. Target coverages in the two types of plans were similar, but automatically generated plans had less irradiation of healthy tissue. In 94% of the evaluations, the autoplans scored at least as high as the previously delivered clinical plans. For all patients, the Auto-Planning tool produced clinically acceptable head and neck treatment plans without any manual intervention, except for the initial target and OAR delineations. The main benefit of the method is the likely improvement in the overall treatment quality since consistent, high-quality plans are generated which even can be further optimized, if necessary. This makes it possible for the dosimetrist to focus more time on difficult dose planning goals and to spend less time on the more tedious parts of the planning process.


ROC analysis of statistical methods used in functional MRI: individual subjects.
The complicated structure of fMRI signals and associated noise sources make it difficult to assess the validity of various steps involved in the statistical analysis of brain activation. Most methods used for fMRI analysis assume that observations are independent and that the noise can be treated as white gaussian noise. These assumptions are usually not true but it is difficult to assess how severely these assumptions are violated and what are their practical consequences. In this study a direct comparison is made between the power of various analytical methods used to detect activations, without reference to estimates of statistical significance. The statistics used in fMRI are treated as metrics designed to detect activations and are not interpreted probabilistically. The receiver operator characteristic (ROC) method is used to compare the efficacy of various steps in calculating an activation map in the study of a single subject based on optimizing the ratio of the number of detected activations to the number of false-positive findings. The main findings are as follows: Preprocessing. The removal of intensity drifts and high-pass filtering applied on the voxel time-course level is beneficial to the efficacy of analysis. Temporal normalization of the global image intensity, smoothing in the temporal domain, and low-pass filtering do not improve power of analysis. Choices of statistics. the cross-correlation coefficient and t-statistic, as well as nonparametric Mann-Whitney statistics, prove to be the most effective and are similar in performance, by our criterion. Task design. the proper design of task protocols is shown to be crucial. In an alternating block design the optimal block length is be approximately 18 s. Spatial clustering. an initial spatial smoothing of images is more efficient than cluster filtering of the statistical parametric activation maps.


ICTV Virus Taxonomy Profile: Aoguangviridae 2023.
The family Aoguangviridae includes dsDNA viruses that have been associated with marine archaea. Currently, members of this virus family are known through metagenomics. Virions are predicted to consist of an icosahedral capsid and a helical tail, characteristic of members in the class Caudoviricetes. Aoguangviruses have some of the largest genomes among archaeal viruses and possess most of the components of the DNA replication machinery as well as auxiliary functions. The family Aoguangviridae includes the species Aobingvirus yangshanense. Many unclassified relatives of this virus group, referred to as 'magroviruses', have been discovered by metagenomics in globally distributed marine samples. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Aoguangviridae, which is available at ictv.global/report/aoguangviridae.


Development of a Framework for the Communication System Based on KNX for an Interactive Space for UX Evaluation.
Domotics (Home Automation) aims to improve the quality of life of people by integrating intelligent systems within inhabitable spaces. While traditionally associated with smart home systems, these technologies have potential for User Experience (UX) research. By emulating environments to test products and services, and integrating non-invasive user monitoring tools for emotion recognition, an objective UX evaluation can be performed. To achieve this objective, a testing booth was built and instrumented with devices based on KNX, an international standard for home automation, to conduct experiments and ensure replicability. A framework was designed based on Python to synchronize KNX systems with emotion recognition tools; the synchronization of these data allows finding patterns during the interaction process. To evaluate this framework, an experiment was conducted in a simulated laundry room within the testing booth to analyze the emotional responses of participants while interacting with prototypes of new detergent bottles. Emotional responses were contrasted with traditional questionnaires to determine the viability of using non-invasive methods. Using emulated environments alongside non-invasive monitoring tools allowed an immersive experience for participants. These results indicated that the testing booth can be implemented for a robust UX evaluation methodology.


[HIV/AIDS: an exploration of the knowledge, attitude, infection risk perceptions, and willingness to care of nurses].
The number of people infected with HIV/AIDS continues to increase across the world. The awareness of HIV/AIDS and attitudes toward this disease among nurses and their willingness to care for those infected directly impacts upon the quality of HIV/AIDS-patient care. This study explores the knowledge, attitudes, infection-risk perceptions, and willingness to care for HIV/AIDS patients among nurses and the correlations among these variables. This study used a descriptive, correlational design. Scales on HIV/AIDS-related knowledge, attitudes, perceived risk of infection, and willingness to care were used to collect data from 219 nurses who attended the course series on HIV/AIDS held by the Nurses AIDS Prevention Foundation in 2010. The mean score for HIV/AIDS knowledge was 79.6%, with knowledge related to disease transmission pathways earning the highest score and knowledge related to HIV/AIDS protective measures earning the lowest. Participating nurses with higher knowledge scores held a more positive attitude toward HIV/AIDS (p < .001), a lower perceived risk of HIV/AIDS infection (p < .001), and a higher willingness to care for HIV/AIDS-positive patients (p = .001). In addition, those participants who had received in-service HIV/AIDS education training earned higher willingness-to-care scores (p = .046). The results of the present study underscore the importance of HIV/AIDS education and may be referenced by health authorities and hospitals for promoting HIV/AIDS education. Further, the results suggest that nurses with a greater knowledge of HIV/AIDS protection and of prophylaxis after occupational exposure are more willing to care for HIV/AIDS patients.


Tests to detect and inform the diagnosis of root caries.
Root caries is a well-recognised disease, with increasing prevalence as populations age and retain more of their natural teeth into later life. Like coronal caries, root caries can be associated with pain, discomfort, tooth loss, and contribute significantly to poorer oral health-related quality of life in the elderly. Supplementing the visual-tactile examination could prove beneficial in improving the accuracy of early detection and diagnosis. The detection of root caries lesions at an early stage in the disease continuum can inform diagnosis and lead to targeted preventive therapies and lesion arrest. To assess the diagnostic test accuracy of index tests for the detection and diagnosis of root caries in adults, used alone or in combination with other tests. Cochrane Oral Health's Information Specialist undertook a search of the following databases: MEDLINE Ovid (1946 to 31 December 2018); Embase Ovid (1980 to 31 December 2018); US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov, to 31 December 2018); and the World Health Organization International Clinical Trials Registry Platform (to 31 December 2018). We studied reference lists as well as published systematic review articles. We included diagnostic accuracy study designs that compared one or more index tests (laser fluorescence, radiographs, visual examination, electronic caries monitor (ECM), transillumination), either independently or in combination, with a reference standard. This included prospective studies that evaluated the diagnostic accuracy of single index tests and studies that directly compared two or more index tests. In vitro and in vivo studies were eligible for inclusion but studies that artificially created carious lesions were excluded. Two review authors extracted data independently and in duplicate using a standardised data extraction and quality assessment form based on the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) specific to the review context. Estimates of diagnostic test accuracy were expressed as sensitivity and specificity with 95% confidence intervals (CI) for each dataset. We planned to use hierarchical models for data synthesis and explore potential sources of heterogeneity through meta-regression. Four cross-sectional diagnostic test accuracy studies providing eight datasets with data from 4997 root surfaces were analysed. Two in vitro studies evaluated secondary root caries lesions on extracted teeth and two in vivo studies evaluated primary root caries lesions within the oral cavity. Four studies evaluated laser fluorescence and reported estimates of sensitivity ranging from 0.50 to 0.81 and specificity ranging from 0.40 to 0.80. Two studies evaluated radiographs and reported estimates of sensitivity ranging from 0.40 to 0.63 and specificity ranging from 0.31 to 0.80. One study evaluated visual examination and reported sensitivity of 0.75 (95% CI 0.48 to 0.93) and specificity of 0.38 (95% CI 0.14 to 0.68). One study evaluated the accuracy of radiograph and visual examination in combination and reported sensitivity of 0.81 (95% CI 0.54 to 0.96) and specificity of 0.54 (95% CI 0.25 to 0.81). Given the small number of studies and important differences in the clinical and methodological characteristics of the studies we were unable to pool the results. Consequently, we were unable to formally evaluate the comparative accuracy of the different tests considered in this review. Using QUADAS-2 we judged all four studies to be at overall high risk of bias, but only two to have applicability concerns (patient selection domain). Reasons included bias in the selection process, use of post hoc (data driven) positivity thresholds, use of an imperfect reference standard, and use of extracted teeth. We downgraded the certainty of the evidence due to study limitations and serious imprecision of the results (downgraded two levels), and judged the certainty of the evidence to be very low. Visual-tactile examination is the mainstay of root caries detection and diagnosis; however, due to the paucity of the evidence base and the very low certainty of the evidence we were unable to determine the additional benefit of adjunctive diagnostic tests for the detection and diagnosis of root caries.


Analysis of concert hall acoustics via visualizations of time-frequency and spatiotemporal responses.
Acousticians and other practitioners alike often describe acoustic conditions in performance spaces with standard objective parameters. Apart from a few exceptions, the parameters are calculated by integrating the sound energy of the impulse responses over time; this makes them inadequate for researching the acoustics in detail, especially in the early part of the room impulse response. This paper proposes a method based on time-frequency and spatiotemporal presentations to overcome the lack of detail in the standard analysis. In brief, the proposed methods visualize the cumulative development of the sound field as a function of frequency or direction by forward-integrating the energy in the impulse response in short time frames. Analysis on the measurements from six concert halls concentrates particularly on interpreting the results in light of the seat dip effect. Earlier research has concluded that the seat dip effect is reduced by reflection from low overhead surfaces. In contrast, the current results indicate that the seat dip attenuation in the frequency response is corrected the best when the hall provides most lateral reflections. These findings suggest that the proposed analysis is suitable for explaining concert hall acoustics in detail.


Ultrastructure and permeability of immature neural and extraneural blood vessels.
The ultrastructure and permeability to the marker horseradish peroxidase in the leptomeningeal and neural vessels of the optic lobes, and in the wing bud vessels, were compared, during early stages of chick embryo vasculogenesis, in order to ascertain whether young neural vessels, like mature ones, possess structural specificity preventing the free transport of molecules through their wall (blood-brain barrier). The results demonstrated that immature endothelia are always permeable to the tracer, since the marker passes the vessel wall through the interendothelial clefts (paracellular route) as well as by endo-exocytotic mechanisms (transcellular route). Nevertheless, the transport by vesicles is somewhat reduced in the neural vessels compared to that in the extraneural ones, suggesting that the former may be influenced by the surrounding neuropile to differentiate in a specific manner right from early development.


Methylarcula marina gen. nov., sp. nov. and Methylarcula terricola sp. nov.: novel aerobic, moderately halophilic, facultatively methylotrophic bacteria from coastal saline environments.
A new genus, Methylarcula, with two new species, Methylarcula marina and Methylarcula terricola, are proposed for strains h1T and h37T of moderately halophilic facultatively methylotrophic bacteria isolated from the coastal saline habitats. These methylobacteria are aerobic, Gram-negative, asporogenous, non-motile, colourless rods that multiply by binary fission. Their cellular fatty acids profiles consist primarily of straight-chain unsaturated (C18:1; 70-80%), saturated (C18:0; 14-16%) and cyclopropane (C19:0; 5-6%) acids. The major ubiquinone is Q-10. The dominant phospholipids are phosphatidylethanolamine and phosphatidylcholine. Both strains could use methylamine, some sugars and organic acids as carbon and energy sources. They grew well under optimal conditions (29-35 degrees C, pH 7.5-8.5, 0.5-1.0 M NaCl) and accumulated intracellularly poly-beta-hydroxybutyrate and the compatible solute ectoine. The ectoine pool was found to increase upon increasing the external NaCl concentration and accounted for 18% of the dry cellular weight. Both strains oxidized methylamine by the N-methylglutamate (N-MG) pathway enzymes (gamma-glutamylmethylamide synthetase/lyase and N-MG synthetase/lyase) to formaldehyde and assimilated it via the icl- serine pathway. The DNA G+C content was 60-4 mol% for Methylarcula marina h1T and 57.1 mol% for Methylarcula terricola h37T. The DNA-DNA hybridization value between strains hl and h37 was 25-30%, although they had a low level of DNA relatedness (5-7%) with the type strains of the serine pathway methylobacteria belonging to the genera Methylobacterium, Aminobacter, Methylorhabdus and Methylopila. A comparative 16S rDNA sequence-based phylogenetic analysis placed the two species of Methylarcula into a separate branch of the alpha-3 subclass of the Proteobacteria. The type strains of the new species are Methylarcula marina h1T (= VKM B-2159T) and Methylarcula terricola h37T (= VKM B-2160T).


How and where the education dollar is spent.
Locally elected school boards have the authority and responsibility to decide how school budgets will be spent. In doing so, however, they must balance multiple funding restrictions and competing priorities. Despite great variance in local circumstances, most school districts have remarkably similar spending patterns, generally allocating from 60% to 63% of their budget to instruction and dividing the remainder among student services such as health services, counseling, and speech therapy; administration; building operation and maintenance; and food services and transportation. Polls show that many districts are attempting to delegate more decisions over resource allocation to the school site level. Research is just beginning to show what aspects of school site decision making are associated with improved teaching and learning.


A Scalable Privacy-preserving Data Generation Methodology for Exploratory Analysis.
Big data coupled with precision medicine has the potential to significantly improve our understanding and treatment of complex disorders, such as cancer, diabetes, depression, etc. However, the essential problem is that data are stuck in silos, and it is difficult to precisely identify which data would be relevant and useful for any particular type of analysis. While the process to acquire and access biomedical data requires significant effort, in many cases the data may not provide much insight to the problem at hand. Therefore, there is a need to be able to measure the utility/relevance of additional datasets for a particular biomedical research task without direct access to the data. Towards this, in this paper, we develop a privacy-preserving approach to create synthetic data that can provide a firstorder approximation of utility. We evaluate the proposed approach with several biomedical datasets in the context of regression and classification tasks and discuss how it can be incorporated into existing data management systems such as REDCap.


Passive Q Switching of a Diode-Pumped 946-nm Nd:YAG Laser with 1.6-W Average Output Power.
As much as 1.6-W average output power was emitted in a simple setup from a diffusion-bonded Nd:YAG rod with 70-100-ns Q-switched pulses at 946 nm and repetition frequencies between 15 and 45 kHz at 22-W incident diode-pump power. A Cr(4+):YAG crystal with a bleachable loss of approximately 2.5% and a length of 0.5 mm was used as a saturable absorber. The extraction efficiency was 47% in comparison with the continuous-wave laser output power of 3.37 W in the free-running regime.


Histopathologic study of the human eustachian tube and its surrounding structures following irradiation for carcinoma of the oropharynx.
To describe a histopathologic analysis of a human temporal bone demonstrating patulous changes of the eustachian tube (ET) and its surrounding structures following radiation therapy. Retrospective histopathologic case review and comparison with an age-matched control. Elizabeth McCullough Knowles Otopathology Laboratory, University of Pittsburgh School of Medicine, Pittsburgh, Pa. A widened patulous ET was verified by demonstrating fibrous tissue replacement of the surrounding supporting structures related to the ET. The ET lumen was patulous and wider than the control case. Ostmann fatty tissue, the levator veli palatini muscle, and submucosal glands around the ET cartilage were replaced by dense connective tissue. This is the first histopathologic report, to our knowledge, demonstrating the effects on the ET lumen and supporting structures following acute weight loss, possible tumor infiltration, and radiation changes for carcinoma of the oropharynx.


Prediction of Cerebral Hyperperfusion after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis by Three-Dimensional-Time-of-Flight Magnetic Resonance Angiography in Adult Patients with Moyamoya Disease.
Superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis is an effective surgical procedure for adult patients with moyamoya disease (MMD) and is known to have the potential to prevent cerebral ischemia and/or hemorrhagic stroke. Cerebral hyperperfusion (CHP) syndrome is one of the serious complications of this procedure that can result in deleterious outcomes, such as delayed intracerebral hemorrhage, but the prediction of CHP before revascularization surgery remains challenging. The present study evaluated the diagnostic value of preoperative three-dimensional (3D)-time-of-flight (TOF) magnetic resonance angiography (MRA) for predicting CHP after STA-MCA anastomosis for MMD. The signal intensity of the peripheral portion of the intracranial major arteries, such as the anterior cerebral artery (ACA), MCA, and posterior cerebral artery (PCA) ipsilateral to STA-MCA anastomosis, on preoperative MRA was graded (0-2 in each vessel) according to the ability to visualize each vessel on 97 affected hemispheres in 83 adult MMD patients. Local cerebral blood flow (CBF) at the site of anastomosis was quantitatively measured by N-isopropyl-p-[123I]-iodoamphetamine single-photon emission computed tomography 1 and 7 days after surgery, in addition to the preoperative CBF value at the corresponding area. Then, we investigated the correlation between the preoperative MRA score and the development of CHP. The CHP phenomenon 1 day after STA-MCA anastomosis (local CBF increase over 150% compared with the preoperative value) was evident in 27 patients (27/97 hemispheres; 28%). Among them, 8 (8 hemispheres) developed CHP syndrome. Multivariate analysis revealed that the hemispheric MRA score (0-6), the summed ACA, MCA, and PCA scores for the affected hemisphere, was significantly associated with the development of CHP syndrome (p = 0.011). The hemispheric MRA score was also significantly correlated with the CHP phenomenon, either symptomatic or asymptomatic (p < 0.001). The signal intensity of the intracranial major arteries, including the ACA, MCA, and PCA, on preoperative 3D-TOF MRA may identify adult MMD patients at higher risk for CHP after direct revascularization surgery.


The concept of structured treatment interruptions in the management of patients with human immunodeficiency virus (HIV) disease: where are we currently?
The failure to achieve viral eradication with currently available antiretroviral agents has spawned new approaches to limiting drug exposure. Highly active antiretroviral therapy (HAART) lowers morbidity and mortality of HIV disease but cannot eradicate the virus from the body. Structured treatment interruptions (STIs) have been proposed as a strategy to minimize the toxicities of HAART while providing a mechanism to enhance HIV-specific immunity. STIs have been investigated in three distinct clinical scenarios: during acute infection, during chronic infection, and during virologic failure. However, many questions still need to be answered in controlled trials before STIs can be adopted in clinical practice.


Evolution of base-substitution gradients in primate mitochondrial genomes.
Inferences of phylogenies and dates of divergence rely on accurate modeling of evolutionary processes; they may be confounded by variation in substitution rates among sites and changes in evolutionary processes over time. In vertebrate mitochondrial genomes, substitution rates are affected by a gradient along the genome of the time spent being single-stranded during replication, and different types of substitutions respond differently to this gradient. The gradient is controlled by biological factors including the rate of replication and functionality of repair mechanisms; little is known, however, about the consistency of the gradient over evolutionary time, or about how evolution of this gradient might affect phylogenetic analysis. Here, we evaluate the evolution of response to this gradient in complete primate mitochondrial genomes, focusing particularly on A-->G substitutions, which increase linearly with the gradient. We developed a methodology to evaluate the posterior probability densities of the response parameter space, and used likelihood ratio tests and mixture models with different numbers of classes to determine whether groups of genomes have evolved in a similar fashion. Substitution gradients usually evolve slowly in primates, but there have been at least two large evolutionary jumps: on the lineage leading to the great apes, and a convergent change on the lineage leading to baboons (Papio). There have also been possible convergences at deeper taxonomic levels, and different types of substitutions appear to evolve independently. The placements of the tarsier and the tree shrew within and in relation to primates may be incorrect because of convergence in these factors.


Cannabidiol enhances morphine antinociception, diminishes NMDA-mediated seizures and reduces stroke damage via the sigma 1 receptor.
Cannabidiol (CBD), the major non-psychotomimetic compound present in the Cannabis sativa plant, exhibits therapeutic potential for various human diseases, including chronic neurodegenerative diseases, such as Alzheimer's and Parkinson's, ischemic stroke, epilepsy and other convulsive syndromes, neuropsychiatric disorders, neuropathic allodynia and certain types of cancer. CBD does not bind directly to endocannabinoid receptors 1 and 2, and despite research efforts, its specific targets remain to be fully identified. Notably, sigma 1 receptor (σ1R) antagonists inhibit glutamate N-methyl-D-aspartate acid receptor (NMDAR) activity and display positive effects on most of the aforesaid diseases. Thus, we investigated the effects of CBD on three animal models in which NMDAR overactivity plays a critical role: opioid analgesia attenuation, NMDA-induced convulsive syndrome and ischemic stroke. In an in vitro assay, CBD disrupted the regulatory association of σ1R with the NR1 subunit of NMDAR, an effect shared by σ1R antagonists, such as BD1063 and progesterone, and prevented by σ1R agonists, such as 4-IBP, PPCC and PRE084. The in vivo administration of CBD or BD1063 enhanced morphine-evoked supraspinal antinociception, alleviated NMDA-induced convulsive syndrome, and reduced the infarct size caused by permanent unilateral middle cerebral artery occlusion. These positive effects of CBD were reduced by the σ1R agonists PRE084 and PPCC, and absent in σ1R-/- mice. Thus, CBD displays antagonist-like activity toward σ1R to reduce the negative effects of NMDAR overactivity in the abovementioned experimental situations.


Mass drug administration of ivermectin and dihydroartemisinin-piperaquine against malaria in settings with high coverage of standard control interventions: a cluster-randomised controlled trial in The Gambia.
Although the malaria burden has substantially decreased in sub-Saharan Africa, progress has stalled. We assessed whether mass administration of ivermectin (a mosquitocidal drug) and dihydroartemisinin-piperaquine (an antimalarial treatment) reduces malaria in The Gambia, an area with high coverage of standard control interventions. This open-label, cluster-randomised controlled trial was done in the Upper River region of eastern Gambia. Villages with a baseline Plasmodium falciparum prevalence of 7-46% (all ages) and separated from each other by at least 3 km to reduce vector spillover were selected. Inclusion criteria were age and anthropometry (for ivermectin, weight of ≥15 kg; for dihydroartemisinin-piperaquine, participants older than 6 months); willingness to comply with trial procedures; and written informed consent. Villages were randomised (1:1) to either the intervention (ivermectin [orally at 300-400 μg/kg per day for 3 consecutive days] and dihydroartemisinin-piperaquine [orally depending on bodyweight] plus standard control interventions) or the control group (standard control interventions) using computer-based randomisation. Laboratory staff were masked to the origin of samples. In the intervention group, three rounds of mass drug administration once per month with ivermectin and dihydroartemisinin-piperaquine were given during two malaria transmission seasons from Aug 27 to Oct 31, 2018, and from July 15 to Sept 30, 2019. Primary outcomes were malaria prevalence by qPCR at the end of the second intervention year in November 2019, and Anopheles gambiae (s l) parous rate, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03576313. Between Nov 20 and Dec 7, 2017, 47 villages were screened for eligibility in the study. 15 were excluded because the baseline malaria prevalence was less than 7% (figure 1). 32 villages were enrolled and randomised to either the intervention or control group (n=16 in each group). The study population was 10 638, of which 4939 (46%) participants were in intervention villages. Coverage for dihydroartemisinin-piperaquine was between 49·0% and 58·4% in 2018, and between 76·1% and 86·0% in 2019; for ivermectin, coverage was between 46·9% and 52·2% in 2018, and between 71·7% and 82·9% in 2019. In November 2019, malaria prevalence was 12·8% (324 of 2529) in the control group and 5·1% (140 of 2722) in the intervention group (odds ratio [OR] 0·30, 95% CI 0·16-0·59; p<0·001). A gambiae (s l) parous rate was 83·1% (552 of 664) in the control group and 81·7% (441 of 540) in the intervention group (0·90, 0·66-1·25; p=0·537). In 2019, adverse events were recorded in 386 (9·7%) of 3991 participants in round one, 201 (5·4%) of 3750 in round two, and 168 (4·5%) of 3752 in round three. None of the 11 serious adverse events were related to the intervention. The intervention was safe and well tolerated. In an area with high coverage of standard control interventions, mass drug administration of ivermectin and dihydroartemisinin-piperaquine significantly reduced malaria prevalence; however, no effect of ivermectin on vector parous rate was observed. Joint Global Health Trials Scheme. For the French translation of the abstract see Supplementary Materials section.


New high-temperature Chiorella.
Growth characteristics of Chlorella 1-9-30, a new strain of green, high-temperature algae, are compared with those of the widely used Chlorella 7-11-05. Under comparable conditions. Chlorella 1-9-30 has the same temperature range for growth as has Chlorella 7-11-05, but it generally has a higher growth rate. It also differs from Chlorella 7-11-05 morphologically. Because of its high capacity for organic synthesis, Chlorella 1-9-30 may be useful in biochemical, biophysical, and physiological research.


[A useful test for evaluating the needs for support of family members--help for an aged parent at home: a tool with potential application in French-speaking Europe].
The Family Caregivers Support Agreement (FCSA) tool, based on a caregiver-service provider partnership approach to assess the support needs of family caregivers of a home-living aging relative, was field-tested to document its relevance for use in Quebec (Canada) practice settings. The FCSA tool is a modified version of the Carers Outcome Assessment Tool, initially developed as the result of an Anglo-Swedish Study. The field test was conducted with 17 French- and English-speaking caregivers and revealed numerous unmet caregiver needs, especially of a psycho-educational nature. The use of the FCSA tool lead to an identification of homecare support services which corresponded to caregiver needs and expectations. According to the homecare services providers interviewed, the FCSA tool offers a structured and flexible approach that facilitates the identification of services sensitive to caregiver needs. The instrument allows concretizing the partnership process, in particular, by bringing to light the unique needs of individual caregivers, empowering caregivers by considering them active participants in decision making, and fostering a proper fit between services and needs. Results are in line with those of other studies, suggesting that the caregiver role entails common core needs and that the impact of the FCSA tool is comparable regardless of practice setting. All told, the FCSA tool could potentially be applied in the French-speaking Europe.


Debundling of single-walled nanotubes by dilution: observation of large populations of individual nanotubes in amide solvent dispersions.
Large-scale debundling of single-walled nanotubes has been demonstrated by dilution of nanotube dispersions in the solvent N-methyl-2-pyrrolidone (NMP). At high concentrations some very large (approximately 100 s of micrometers) nanotube aggregates exist that can be removed by mild centrifugation. By measurement of the absorbance before and after centrifugation as a function of concentration the relative aggregate and dispersed nanotube concentrations can be monitored. No aggregates are observed below CNT approximately 0.02 mg/mL, suggesting that this can be considered the nanotube dispersion limit in NMP. After centrifugation, the dispersions are stable against sedimentation and further aggregation for a period of weeks at least. Atomic force microscopy (AFM) studies on deposited films reveal that the bundle diameter distribution decreases dramatically as concentration is decreased. Detailed data analysis suggests the presence of an equilibrium bundle number density and that the dispersions self-arrange themselves to always remain close to the dilute/semidilute boundary. A population of individual nanotubes is always observed that increases with decreasing concentration until almost 70% of all dispersed objects are individual nanotubes at a concentration of 0.004 mg/mL. The number density of individual nanotubes peaks at a concentration of approximately 10(-2) mg/mL. Both the mass fraction and the partial concentration of individual nanotubes can also be measured and behave in similar fashion. Comparison of the number density and partial concentration also of individual nanotubes reveals that the individual nanotubes have average molar masses of approximately 700,000 g/mol. The presence of individual nanotubes in NMP dispersion was confirmed by photoluminescence spectroscopy. Concentration dependence of the photoluminescence intensity confirms that the AFM measurements reflect the diameter distributions in situ. In addition, Raman spectroscopy confirms the presence of large quantities of individual nanotubes in the deposited films. Finally, the nature of the solvent properties required for dispersion are discussed.


GFPT1-myasthenia: clinical, structural, and electrophysiologic heterogeneity.
To identify patients with GFPT1-related limb-girdle myasthenia and analyze phenotypic consequences of the mutations. We performed genetic analysis, histochemical, immunoblot, and ultrastructural studies and in vitro electrophysiologic analysis of neuromuscular transmission. We identified 16 recessive mutations in GFPT1 in 11 patients, of which 12 are novel. Ten patients had slowly progressive limb-girdle weakness responsive to cholinergic agonists with onset between infancy and age 19 years. One patient (no. 6) harbored a nonsense mutation and a second mutation that disrupts the muscle-specific GFPT1 exon. This patient never moved in utero, was apneic and arthrogrypotic at birth, and was bedfast, tube-fed, and barely responded to therapy at age 6 years. Histochemical studies in 9 of 11 patients showed tubular aggregates in 6 and rimmed vacuoles in 3. Microelectrode studies of intercostal muscle endplates in 5 patients indicated reduced synaptic response to acetylcholine in 3 and severely reduced quantal release in patient 6. Endplate acetylcholine receptor content was moderately reduced in only one patient. The synaptic contacts were small and single or grape-like, and quantitative electron microscopy revealed hypoplastic endplate regions. Numerous muscle fibers of patient 6 contained myriad dilated and degenerate vesicular profiles, autophagic vacuoles, and bizarre apoptotic nuclei. Glycoprotein expression in muscle was absent in patient 6 and reduced in 5 others. GFPT1-myasthenia is more heterogeneous than previously reported. Different parameters of neuromuscular transmission are variably affected. When disruption of muscle-specific isoform determines the phenotype, this has devastating clinical, pathologic, and biochemical consequences.


A Multivocal Literature Review on Growing Social Engineering Based Cyber-Attacks/Threats During the COVID-19 Pandemic: Challenges and Prospective Solutions.
The novel coronavirus (COVID-19) pandemic has caused a considerable and long-lasting social and economic impact on the world. Along with other potential challenges across different domains, it has brought numerous cybersecurity challenges that must be tackled timely to protect victims and critical infrastructure. Social engineering-based cyber-attacks/threats are one of the major methods for creating turmoil, especially by targeting critical infrastructure, such as hospitals and healthcare services. Social engineering-based cyber-attacks are based on the use of psychological and systematic techniques to manipulate the target. The objective of this research study is to explore the state-of-the-art and state-of-the-practice social engineering-based techniques, attack methods, and platforms used for conducting such cybersecurity attacks and threats. We undertake a systematically directed Multivocal Literature Review (MLR) related to the recent upsurge in social engineering-based cyber-attacks/threats since the emergence of the COVID-19 pandemic. A total of 52 primary studies were selected from both formal and grey literature based on the established quality assessment criteria. As an outcome of this research study; we discovered that the major social engineering-based techniques used during the COVID-19 pandemic are phishing, scamming, spamming, smishing, and vishing, in combination with the most used socio-technical method: fake emails, websites, and mobile apps used as weapon platforms for conducting successful cyber-attacks. Three types of malicious software were frequently used for system and resource exploitation are; ransomware, trojans, and bots. We also emphasized the economic impact of cyber-attacks performed on different organizations and critical infrastructure in which hospitals and healthcare were on the top targeted infrastructures during the COVID-19 pandemic. Lastly, we identified the open challenges, general recommendations, and prospective solutions for future work from the researcher and practitioner communities by using the latest technology, such as artificial intelligence, blockchain, and big data analytics.


Optimal Contribution Selection in Highly Fecund Species With Overlapping Generations.
Optimal contributions approaches to parental selection in closed breeding populations aim to maximize genetic gains, while restraining long-term inbreeding. The adoption of optimal contribution selection (OCS) in highly fecund outcrossing species presents a number of challenges not applicable to species of low fecundity (e.g., livestock) for which they were developed. This is particularly true if overlapping-generations or rolling-front breeding strategies are applied, in which case the number of individuals per family in juvenile (i.e., sexually immature) age groups is not necessarily known but is likely to be large. In these circumstances, conventional OCS procedures must be modified or a large number of dummy individuals defined, making computations onerous. Here, an approach to OCS is presented that involves the use of "between-family relationship matrices" instead of "between-individual relationship matrices." The method is applicable to breeding programs involving highly fecund outcrossing species with overlapping generations, including circumstances where the number of juveniles per family is unknown but large.


[Analyses on the isolation and characterization of canine rabies virus isolates in Henan].
To analyze the genetic characteristics of two rabies virus isolates from Henan province and to compare their relations hip with known rabies virus isolates and vaccine strains. Rabies viral antigens were detected in 100 canine brains by immunofluorescence assay method. Rabies virus was isolated through inoculating the suspensions of positive brains into suckling mice. N gene and G were amplified by RT-PCR and sequenced. Phylogenetic trees were constructed for the analysis on genetic characteristics of rabies virus. Two rabies virus strains were isolated (Henan Hb1 and Henan Sq1). Data from sequential comparison revealed that the nucleotide and amino acid identities of N and G gene between the two isolates were 99.3% and 98.9%, and 98.7% and 98.4% respectively. The two isolates were more closely related to CTN, with the homogeny of N gene and G gene as 89.1% and 85.6%-85.7% at the nucleotide level, but 97.6%-98.0% and 92.3% at the amino acid level respectively, than to other vaccine strains. When comparing with other known viruses including Chinese isolates, the two stains shared closer identity with the isolates from Indonesia, and the rates of homogeny of N and G gene were 92.1%-93.2% and 91.9%-92.1% at the nucleotide level, 97.5%-98.6% and 96.0%-96.2% at the amino acid level, respectively. Data from the deduced amino acid sequences revealed that some amino acid residues including the residues in the N and G antigenic sites were substituted in the two isolates. Furthermore, phylogenetic analysis showed that the two isolates were also more closely related to the strains from Indonesia and vaccine strain CTN than to any other known street viruses and vaccine strains. Both Henan Hbl and Henan Sql belonged to genotype 1. However, the N and G gene diverged from known street viruses and vaccine strains at either nucleotide level or amino acid level.


Infection Status of Gnathostoma spinigerum Larvae in Asian Swamp Eels, Monopterus albus, Purchased from Local Markets in Cambodia.
Present study was performed to know the infection status of Gnathostoma sp. larvae in swamp eels from Cambodia. We purchased total 30 Asian swamp eels, Monopterus albus, from local markets in Pursat and Takeo Provinces and Phnom Penh on May and November 2017 and May 2018. All collected eels were transferred to our laboratory with ice and each of them was examined by artificial digestion method. A total of 15 larval gnathostomes (1-5 larvae) were detected from 55.6% (5/9) swamp eels in Pursat Province. No larval gnathostomes were found in 21 swamp eels in Takeo Province and Phnom Penh. The advanced third-stage larvae (AdL3) detected were 2.575-3.825 (3.250) mm in length and 0.375-0.425 (0.386) mm in width. They had the characteristic head bulb (av. 0.104×0.218 mm) with 4 rows of hooklets, long muscular esophagus (1.048 mm), and 2 pairs of cervical sacs (0.615 mm). The number of hooklets in 4 rows on the head bulb was 41, 44, 47, and 50. In scanning electron microscopy, characteristic features were 4 rows of hooklets on the head bulb, cervical papillae, tegumental spines regularly arranged in transverse striations, and anus. The larval gnathostomes were identified as AdL3 of Gnathostoma spinigerum based on the morphological characters. By the present study, it has been confirmed that G. spinigerum larvae are infected in Asian swamp eels, M. albus, in Pursat Province, Cambodia.


Do deepfake videos undermine our epistemic trust? A thematic analysis of tweets that discuss deepfakes in the Russian invasion of Ukraine.
Deepfakes are a form of multi-modal media generated using deep-learning technology. Many academics have expressed fears that deepfakes present a severe threat to the veracity of news and political communication, and an epistemic crisis for video evidence. These commentaries have often been hypothetical, with few real-world cases of deepfake's political and epistemological harm. The Russo-Ukrainian war presents the first real-life example of deepfakes being used in warfare, with a number of incidents involving deepfakes of Russian and Ukrainian government officials being used for misinformation and entertainment. This study uses a thematic analysis on tweets relating to deepfakes and the Russo-Ukrainian war to explore how people react to deepfake content online, and to uncover evidence of previously theorised harms of deepfakes on trust. We extracted 4869 relevant tweets using the Twitter API over the first seven months of 2022. We found that much of the misinformation in our dataset came from labelling real media as deepfakes. Novel findings about deepfake scepticism emerged, including a connection between deepfakes and conspiratorial beliefs that world leaders were dead and/or replaced by deepfakes. This research has numerous implications for future research, societal media platforms, news media and governments. The lack of deepfake literacy in our dataset led to significant misunderstandings of what constitutes a deepfake, showing the need to encourage literacy in these new forms of media. However, our evidence demonstrates that efforts to raise awareness around deepfakes may undermine trust in legitimate videos. Consequentially, news media and governmental agencies need to weigh the benefits of educational deepfakes and pre-bunking against the risks of undermining truth. Similarly, news companies and media should be careful in how they label suspected deepfakes in case they cause suspicion for real media.


Developing an Instrumented Measure of Upper Limb Function in Friedreich Ataxia.
Upper limb function for people with Friedreich ataxia determines capacity to participate in daily activities. Current upper limb measures available do not fully capture impairments related to Friedreich ataxia. We have developed an objective measure, the Ataxia Instrumented Measure-Spoon (AIM-S), which consists of a spoon equipped with a BioKin wireless motion capture device, and algorithms that analyse these signals, to measure ataxia of the upper limb during the pre-oral phase of eating. The aim of this study was to evaluate the AIM-S as a sensitive and functionally relevant clinical outcome for use in clinical trials. A prospective longitudinal study evaluated the capacity of the AIM-S to detect change in upper limb function over 48 weeks. Friedreich ataxia clinical severity, performance on the Nine-Hole Peg Test and Box and Block Test and responses to a purpose-designed questionnaire regarding acceptability of AIM-S were recorded. Forty individuals with Friedreich ataxia and 20 control participants completed the baseline assessment. Thirty individuals with Friedreich ataxia completed the second assessment. The sensitivity of the AIM-S to detect deterioration in upper limb function was greater than other measures. Patient-reported outcomes indicated the AIM-S reflected a daily activity and was more enjoyable to complete than other assessments. The AIM-S is a more accurate, less variable measure of upper limb function in Friedreich ataxia than existing measures. The AIM-S is perceived by individuals with Friedreich ataxia to be related to everyday life and will permit individuals who are non-ambulant to be included in future clinical trials.


From 2-methylimidazole to 1,2,3-triazole: a topological transformation of ZIF-8 and ZIF-67 by post-synthetic modification.
Bridging ligand replacement in zeolitic imidazolate frameworks, ZIF-8 and ZIF-67, by 1,2,3-triazole was investigated. A complete substitution of 2-methylimidazole by 1,2,3-triazole resulted in a topological transformation of the parent framework from a sodalite (SOD) network to a diamond (DIA) network.


Mechanisms of cell signaling by the scavenger receptor CD36: implications in atherosclerosis and thrombosis.
CD36 is a multifunctional membrane receptor present on mononuclear phagocytes, platelets, and other cells that serves as a scavenger receptor for oxidized phospholipids, apoptotic cells and certain microbial pathogens. On macrophages, CD36 interaction with oxidized LDL (oxLDL) triggers a signaling response that is pro-inflammatory and pro-atherogenic. The signaling pathway involves activation of src-family kinases, MAP kinases, and Vav family guanine nucleotide exchange factors and results in ligand internalization, foam cell formation and inhibition of migration. On platelets, CD36 interaction with oxLDL and cell-derived microparticles transduces intracellular signals that render them more reactive to low concentrations of classical agonists. In vitro studies and in vivo experiments in CD36 null mice have revealed an important mechanistic role for CD36 in atherosclerosis and thrombosis. Identification of the precise CD36 signaling pathways in specific cells elicited in response to specific ligands may yield novel targets for drug development in athero-thrombotic disorders.


Too many crying babies: a systematic review of pain management practices during immunizations on YouTube.
Early childhood immunizations, although vital for preventative health, are painful and too often lead to fear of needles. Effective pain management strategies during infant immunizations include breastfeeding, sweet solutions, and upright front-to-front holding. However, it is unknown how often these strategies are used in clinical practice. We aimed to review the content of YouTube videos showing infants being immunized to ascertain parents' and health care professionals' use of pain management strategies, as well as to assess infants' pain and distress. A systematic review of YouTube videos showing intramuscular injections in infants less than 12 months was completed using the search terms "baby injection" and "baby vaccine" to assess (1) the use of pain management strategies and (2) infant pain and distress. Pain was assessed by crying duration and pain scores using the FLACC (Face, Legs, Activity, Cry, Consolability) tool. A total of 142 videos were included and coded by two trained individual viewers. Most infants received one injection (range of one to six). Almost all (94%) infants cried before or during the injections for a median of 33 seconds (IQR = 39), up to 146 seconds. FLACC scores during the immunizations were high, with a median of 10 (IQR = 3). No videos showed breastfeeding or the use of sucrose/sweet solutions during the injection(s), and only four (3%) videos showed the infants being held in a front-to-front position during the injections. Distraction using talking or singing was the most commonly used (66%) pain management strategy. YouTube videos of infants being immunized showed that infants were highly distressed during the procedures. There was no use of breastfeeding or sweet solutions and limited use of upright or front-to-front holding during the injections. This systematic review will be used as a baseline to evaluate the impact of future knowledge translation interventions using YouTube to improve pain management practices for infant immunizations.


Variables of the rubella hemagglutination-inhibition test system and their effect on antigen and antibody titers.
A systematic study was made of certain variables of the rubella hemagglutination-inhibition (HI) test system and their effect on antigen and antibody titers. Erythrocytes from pigeons and 1-day-old chicks gave similar antigen and antibody titers, but goose erythrocytes gave lower titers. Indicator erythrocytes could be stored in Alsever's solution at 4 C for as long as 2 weeks without losing sensitivity in hemagglutination (HA) and HI tests. Antigen titers varied by eightfold or more in different diluent systems; titers were generally higher at pH 6.2 than at pH 7.2. A diluent without Ca(2+) gave antigen titers as high as those obtained in diluents with added Ca(2+) ions. Antibody titers also varied in different diluent systems. HEPES diluents at pH 6.2 gave higher antibody titers than those obtained in other diluents, but occasional "false-positive" inhibition reactions were seen. Kaolin suspended in borate saline at pH 9.0 effectively removed inhibitor from sera without absorbing specific antibody, but at pH 7.3 it removed various amounts of specific antibody. Antibody titers of sera treated with kaolin at pH 9.0 were similar to those of sera treated with heparin-MnCl(2); treatment with dextran sulfate-CaCl(2) gave lower antibody titers. Antigens varied widely in sensitivity for detecting HI antibody and in the ability to detect diagnostically significant increases in antibody. Sensitivity in detecting antibody was not related to the HA titer of the antigens. Tween-ether-treated antigens gave lower antibody titers but were more reliable than corresponding untreated antigens for serological diagnosis of infection.


The PI3K/Akt1 pathway enhances steady-state levels of FANCL.
Fanconi anemia hematopoietic stem cells display poor self-renewal capacity when subjected to a variety of cellular stress. This phenotype raises the question of whether the Fanconi anemia proteins are stabilized or recruited as part of a stress response and protect against stem cell loss. Here we provide evidence that FANCL, the E3 ubiquitin ligase of the Fanconi anemia pathway, is constitutively targeted for degradation by the proteasome. We confirm biochemically that FANCL is polyubiquitinated with Lys-48-linked chains. Evaluation of a series of N-terminal-deletion mutants showed that FANCL's E2-like fold may direct ubiquitination. In addition, our studies showed that FANCL is stabilized in a complex with axin1 when glycogen synthase kinase-3β is overexpressed. This result leads us to investigate the potential regulation of FANCL by upstream signaling pathways known to regulate glycogen synthase kinase-3β. We report that constitutively active, myristoylated-Akt increases FANCL protein level by reducing polyubiquitination of FANCL. Two-dimensional PAGE analysis shows that acidic forms of FANCL, some of which are phospho-FANCL, are not subject to polyubiquitination. These results indicate that a signal transduction pathway involved in self-renewal and survival of hematopoietic stem cells also functions to stabilize FANCL and suggests that FANCL participates directly in support of stem cell function.


Arginase and sucrase potential in the fission yeast Schizosaccharomyces pombe.
The induction potentials of 2 enzymes, sucrase and arginase, have been measured in asynchronous and synchronous cultures of the fission yeast Schizosaccharomyces pombe. The effect on potential of inhibiting DNA synthesis is asynchronous cultures has been studied using 2 temperature-sensitive dcd mutants, one blocked in DNA replication and the other blocked in mitosis. The results show that despite inhibition of DNA synthesis, sucrase and arginase potential both continue to increase exponentially for at least a generation of growth after shifting the cdc mutants from the permissive to the restrictive temperature. A second method of inhibiting DNA synthesis, using deoxyadenosine, has also been tested. Cells treated with deoxyadenosine stop the increase in potential for a short period. However, experiments carried out using a cdc mutant together with deoxyadenosine show that the block to the increase in potential is due to a side effect of the inhibitor. It appears that increase in potential is not dependent upon continued DNA replication, and that gene dosage does not control potential in the normal cell cycle. This conclusion is supported by measurements on mutants of different cell sizes. potential is proportional to size (protein content per cell is asynchronous culture) and not to DNA content. Although potential is not gene limited in normal cells, it does appear to be so in the abnormally large cells produced by a cdc block. If cdc mutants of different sizes are grown asynchronously, and DNA synthesis is inhibited by a shift to the restrictive temperature, there is no increase in potential. This critical ratio is different for the 2 enzymes, but for each enzyme it is similar in all the mutants tested. When large cells (produced by a mutant block for 4.5 h) are shifted down in temperature, there are synchronous rounds of DNA synthesis and division and also step doublings in potential. In synchronous cultures of wild type cells, both enzymes show a stepwise doubling of potential at 0.2 of a cycle after DNA replication. In synchronous cultures of cdc mutants blocked either in replication or in mitosis, the potential steps continue with the normal timing observed in wild type cells. This shows that the steps are not dependent on the events of the DNA-division cycle but are controlled by another mechanism. Attainment of a critical size might be part of this mechanism, but tests with size mutants argue against this.


Encephalocele-Associated Drug-Resistant Epilepsy of Adult Onset: Diagnosis, Management, and Outcomes.
Epileptogenic encephaloceles, most frequently located in the temporal lobe, are a known lesional cause of focal epilepsy. Data are limited regarding diagnosis, management, and outcomes of patients with epilepsy in the setting of an encephalocele, because the literature mostly comprises case reports, case series, and retrospective studies. We conducted a broad literature review for articles related to encephaloceles and epilepsy regardless of level of evidence. Hence, this review provides a summary of all available literature related to the topic. Thirty-six scientific reports that fulfilled our inclusion criteria were reviewed. Most reported patients presented with focal impaired awareness seizures and/or generalized tonic-clonic seizures. Although most of the encephaloceles were located in the temporal lobe, we found 5 cases of extratemporal encephaloceles causing epilepsy. More patients who underwent either lesionectomy or lobectomy were seizure free at time of follow-up. In the temporal lobe, there is no clear consensus on the appropriate management for epileptic encephaloceles and further studies are warranted to understand the associated factors and long-term outcomes associated with epilepsy secondary to encephaloceles. Reported data suggest that these patients could be manageable with surgical procedures including lesionectomy or lobectomy. In addition, because of data suggesting similar results between procedures, a more conservative surgery with lesionectomy and defect repair rather than a lobectomy may have lower surgical risks and similar seizure freedom.


Hot-Spot Residue-Based Virtual Screening of Novel Selective Estrogen-Receptor Degraders for Breast Cancer Treatment.
The estrogen-receptor alfa (ERα) is considered pivotal for breast cancer treatment. Although selective estrogen-receptor degraders (SERDs) have been developed to induce ERα degradation and antagonism, their agonistic effect on the uterine tissue and poor pharmacokinetic properties limit further application of ERα; thus, discovering novel SERDs is necessary. The ligand preferentially interacts with several key residues of the protein (defined as hot-spot residues). Improving the interaction with hot-spot residues of ERα offers a promising avenue for obtaining novel SERDs. In this study, pharmacophore modeling, molecular mechanics/generalized Born surface area (MM/GBSA), and amino-acid mutation were combined to determine several hot-spot residues. Focusing on the interaction with these hot-spot residues, hit fragments A1-A3 and A9 were virtually screened from two fragment libraries. Finally, these hit fragments were linked to generate compounds B1-B3, and their biological activities were evaluated. Remarkably, compound B1 exhibited potent antitumor activity against MCF-7 cells (IC50 = 4.21 nM), favorable ERα binding affinity (Ki = 14.6 nM), and excellent ERα degradative ability (DC50 = 9.7 nM), which indicated its potential to evolve as a promising SERD for breast cancer treatment.


Reduction in maternal circulating ouabain impairs offspring growth and kidney development.
Ouabain, a steroid present in the circulation and in various tissues, was shown to affect the growth and viability of various cells in culture. To test for the possible influence of this steroid on growth and viability in vivo, we investigated the involvement of maternal circulating ouabain in the regulation of fetal growth and organ development. We show that intraperitoneal administration of anti-ouabain antibodies to pregnant mice resulted in a >80% decline in the circulating ouabain level. This reduction caused a significant decrease in offspring body weight, accompanied by enlargement of the offspring heart and inhibition of kidney and liver growth. Kidney growth inhibition was manifested by a decrease in the size and number of nephrons. After the reduction in maternal circulating ouabain, kidney expression of cyclin D1 was reduced and the expression of the α1 isoform of the Na(+), K(+)-ATPase was increased. In addition, the elevation of proliferation signals including ERK1/2, p-90RSK, Akt, PCNA, and Ki-67, and a reduction in apoptotic factors such as Bax, caspase-3, and TUNEL were detected. During human pregnancy, the circulating maternal ouabain level increased and the highest concentration of the steroid was found in the placenta. Furthermore, circulating ouabain levels in women with small-for-gestational age neonates were significantly lower than the levels in women with normal-for-gestational age newborns. These results support the notion that ouabain is a growth factor and suggest that a reduction in the concentration of this hormone during pregnancy may increase the risk of impaired growth and kidney development.


High reflectivity multilayer for He-II radiation at 30.4 nm.
SiC/Mg and B(4)C/Mo/Si multilayers were designed for He-II radiation at 30.4 nm. These multilayers were prepared by use of a direct current magnetron sputtering system and measured at the National Synchrotron Radiation Laboratory, China. The measured reflectivities were 38.0% for the SiC/Mg multilayer at an incident angle of 12 deg and 32.5% for the B(4)C/Mo/Si multilayer at 5 deg, respectively. A dual-function multilayer mirror was also designed by use of the aperiodic SiC/Mg multilayer. Annealing experiments were performed to investigate the thermal stability of the SiC/Mg multilayer. The interface of the SiC/Mg multilayer before and after annealing was studied by electron-induced x-ray emission spectra, which evidences the absence of thermal reaction products at the interfaces after annealing.


A framework for evaluating the data-hiding capacity of image sources.
An information-theoretic model for image watermarking and data hiding is presented in this paper. Previous theoretical results are used to characterize the fundamental capacity limits of image watermarking and data-hiding systems. Capacity is determined by the statistical model used for the host image, by the distortion constraints on the data hider and the attacker, and by the information available to the data hider, to the attacker, and to the decoder. We consider autoregressive, block-DCT, and wavelet statistical models for images and compute data-hiding capacity for compressed and uncompressed host-image sources. Closed-form expressions are obtained under sparse-model approximations. Models for geometric attacks and distortion measures that are invariant to such attacks are considered.


Overcoming biomass recalcitrance by combining genetically modified switchgrass and cellulose solvent-based lignocellulose pretreatment.
Decreasing lignin content of plant biomass by genetic engineering is believed to mitigate biomass recalcitrance and improve saccharification efficiency of plant biomass. In this study, we compared two different pretreatment methods (i.e., dilute acid and cellulose solvent) on transgenic plant biomass samples having different lignin contents and investigated biomass saccharification efficiency. Without pretreatment, no correlation was observed between lignin contents of plant biomass and saccharification efficiency. After dilute acid pretreatment, a strong negative correlation between lignin content of plant samples and overall glucose release was observed, wherein the highest overall enzymatic glucan digestibility was 70% for the low-lignin sample. After cellulose solvent- and organic solvent-based lignocellulose fractionation pretreatment, there was no strong correlation between lignin contents and high saccharification efficiencies obtained (i.e., 80-90%). These results suggest that the importance of decreasing lignin content in plant biomass to saccharification was largely dependent on pretreatment choice and conditions.