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Abstract Type I spiral ganglion neurons are peripheral neurons essential for hearing perception. While they can be subdivided in mice based on characteristic gene expression patterns, detailed examinations of these subtypes in primates and humans are lacking. In this study, we investigated the developmental subtypes of spiral ganglion neurons in the common marmoset (Callithrix jacchus). We confirmed that Type I spiral ganglion can be divided based on the characteristic gene expression patterns of several marker genes. However, some combinations of these genes differ from those in rodents, suggesting common marmoset's suitability for advancing our understanding of human cochlear development. Additionally, identifying the essential time points for subtype specifications and subsequent maturation will aid in studying the primate-specific developmental biology of the inner ear. This could lead to new treatment strategies for hearing loss in humans and be valuable for studying age-related hearing loss, as well as designing regenerative therapies.

Abstract Background Intraoperative use of methylene blue has been shown to reduce postoperative complications and recurrence rates in adults. It has however not been assessed if these beneficial effects would also apply to pediatric pilonidal sinus disease with its high recurrence rates. We, therefore, aimed to assess its effects on complications and recurrences in our retrospective exploratory cohort study. Methods Of 55 consecutive children treated in our centre between January 2009 and December 2020, 48 were retrospectively included. We used logistic regression with a priori chosen predictors of intraoperative use of blue dyes, previous surgery for pilonidal sinus disease, and the presence of comorbidities on the composite outcome of complications and recurrence. Cramér’s V was used to explore associations between the use of blue dyes and the extent of resection. Results The median age in our cohort was 15.3 years. Five patients were below 2 years of age, and 24 (50%) of them were males. Chronic diseases were present in 13 (27%) patients, eight had previously been operated on for pilonidal sinus disease, and blue dyes were used in 34 patients (71%). Their intraoperative use was linked to the composite outcome with an odds ratio of 5.41 (95% confidence interval (CI) 1.52–25.34, P = 0.017) as were comorbidities with an odds ratio of 1.86 (95% CI 1.18–3.25, P = 0.014), but not re-do surgery (odds ratio 2.94 (95% CI 0.37 23.42, P = 0.3)). The use of blue dyes was associated with larger resections (Cramér’s V 0.556 (95% CI 0.329–0.74)). Conclusion The intraoperative use of blue dyes was negatively associated with complications and recurrences in pediatric pilonidal sinus disease. However, if blue dyes were used, the extent of resection was also larger. Larger resections had been shown before to be associated with complications and recurrences, too. This potential interaction requires further elucidation in future studies.

Background: Biomarkers to predict the recurrence risk are required to optimize perioperative treatment. Adjuvant chemotherapy for patients with human epidermal growth factor 2-positive (HER2-positive) early breast cancer is decided by pathological responses of neoadjuvant chemotherapy (NAC). However, whether pathological responses are appropriate biomarkers is unclear. Currently, there are several studies using minimal residual disease (MRD) as a predictor of prognosis in solid tumors. However, there is no standard method for detecting MRD. Objectives: This study aimed at prospectively evaluating the relationship between MRD detection and recurrence in Asian patients with HER2-positive early breast cancer. Design: Prospective, observational, single-group, and exploratory. This study will include 60 patients from 2 institutions in Japan and the Philippines. The invasive disease-free survival (IDFS) rates of the MRD-positive and MRD-negative groups are compared in patients with HER2-positive early breast cancer who undergo surgery after receiving NAC. Methods and analysis: Circulating tumor DNA (ctDNA) levels of patients will be evaluated 6 times: before NAC, after NAC, after surgery, and annually after surgery for 3 years. We will analyze the genetic profile of blood and tissue samples using the Todai OncoPanel (TOP) and the methylation level of DNA. The primary endpoint is IDFS. Secondary endpoints include overall survival (OS) and disease-free survival (DFS). Patient enrollment began in June 2022, and new participants are still being recruited. Ethics: This study has been approved by the National Cancer Center Hospital Certified Review Board in March 2022 and has been approved by the Research Ethics Board of the participating center. Discussion: Our findings will contribute to determining whether MRD detection using TOP is useful for predicting the recurrence of HER2-positive early breast cancer. If this is proven, MRD detected by TOP could be used in the future as a biomarker to assist in the de-/escalation of treatment strategies in the next interventional trial, thereby avoiding overtreatment in patients at low risk, and in the addition of intensive treatment modalities for those in patients at high risk.

This study investigates late bloomers—individuals who achieve academic success after initial struggles—in terms of setbacks, coping mechanisms, and support systems. Late bloomers commonly face challenges in subjects like mathematics and English due to conceptual gaps and insufficient foundational skills. Personalized tutoring and targeted educational strategies are crucial interventions for addressing these hurdles and fostering academic growth. Coping mechanisms focus on intrinsic motivation and resilience, including setting clear goals, cultivating supportive peer networks, and drawing inspiration from personal passions like animal enthusiasm, promoting perseverance in overcoming academic obstacles. Support systems from teachers and peers are essential in late bloomers' journeys, providing not only academic guidance but also crucial emotional support that influences their overall well-being. Enhancing teacher training and advocating for inclusive classroom practices are recommended to strengthen these support systems. Methodologically, this study synthesizes qualitative interviews and literature reviews to highlight effective strategies for empowering late bloomers to succeed academically and personally, emphasizing the importance of tailored support and fostering a positive learning environment.

Enteroviruses are a vast genus of positive-sense RNA viruses that cause diseases ranging from common cold to poliomyelitis and viral myocarditis. They encode a membrane-bound AAA+ ATPase, 2C, that has been suggested to serve several roles in virus replication, e.g. as an RNA helicase and capsid assembly factor. Here, we report the reconstitution of full-length, poliovirus 2C's association with membranes. We show that the N-terminal membrane-binding domain of 2C contains a conserved glycine, which is suggested by structure predictions to divide the domain into two amphipathic helix regions, which we name AH1 and AH2. AH2 is the main mediator of 2C oligomerization, and is necessary and sufficient for its membrane binding. AH1 is the main mediator of a novel function of 2C: clustering of membranes. Cryo-electron tomography reveal that several 2C copies mediate this function by localizing to vesicle-vesicle interfaces. 2C-mediated clustering is partially outcompeted by RNA, suggesting a way by which 2C can switch from an early role in coalescing replication organelles and lipid droplets, to a later role where 2C assists RNA replication and particle assembly. 2C is sufficient to recruit RNA to membranes, with a preference for double-stranded RNA (the replicating form of the viral genome). Finally, the in vitro reconstitution revealed that full-length, membrane-bound 2C has ATPase activity and ATP-independent, single-strand ribonuclease activity, but no detectable helicase activity. Together, this study suggests novel roles for 2C in membrane clustering, RNA membrane recruitment and cleavage, and calls into question a role of 2C as an RNA helicase. The reconstitution of functional, 2C-decorated vesicles provides a platform for further biochemical studies into this protein and its roles in enterovirus replication.

Abstract Introduction Demographics are important prognostic factors in malignant diseases. A nationwide analysis concerning the prognostic impact of demographics in head and neck cancer (HNC) patients (HNCP) has not been performed previously. Methods A retrospective analysis of data from the Center for Cancer Registry Data (ZfKD) and the Federal Statistical Office (Destatis) between 2002 and 2017 was performed. A total of 212′920 HNCP were included. Incidence, tumor stage, age development, sex distribution, age‐, residence‐, and diagnosis‐time‐specific survival were examined. Results Mean age of HNCP increased more rapidly than in the general population (slope coefficient: 0.29 vs. 0.20; p 70 years was found. Furthermore, an OS disadvantage was observed for East Germany compared to West Germany (median 47 vs. 60 months; p

Abstract Highly accurate real-time cochlear nerve monitoring to preserve cochlear nerve function is essential for simultaneous cochlear implantation and ipsilateral vestibular schwannoma resection. In the present study, we developed a novel real-time monitoring system that combines dorsal cochlear nucleus action potential monitoring with intracochlear stimulating electrodes (Auditory Nerve Test System, ANTS). We used this system for a case with vestibular schwannoma resection via the translabyrinthine approach. The monitoring system developed in this study detected highly reliable evoked potentials from the cochlear nerve every two seconds continuously during tumor resection. Near-total tumor resection was achieved, and cochlear implantation was performed successfully after confirming the preservation of cochlear nerve function in a case. The patient’s hearing was well compensated by cochlear implantation after surgery. Our novel method continuously achieved real-time monitoring of the cochlear nerve every two seconds during vestibular schwannoma resection. The usefulness of this monitoring system for simultaneous tumor resection and cochlear implantation was demonstrated in the present case. The system developed in this study is compatible with continuous facial nerve monitoring. This highly accurate and novel monitoring method will broaden the number of candidates for this type of surgery in the future.

Abstract Background In the USA, the primary cause of death and morbidity continues to be cardiovascular disease (CVD). Numerous trials have shown that statin medication reduces the likelihood of CVD events; it is a cornerstone of CVD prevention. However, studies have also indicated that up to 60% of the estimated 26.8 million Americans prescribed primary prevention statin treatment are nonadherent during the first year. Multi-component behavioral change technique (BCT) therapies have shown moderate promise in improving medication adherence as well as other positive health behaviors (such as physical activity). However, no research has looked at the duration of multi-component BCT intervention needed to result in a clinically significant improvement in statin adherence behaviors. This study aims to determine the necessary dose of a multi-component BCT intervention (defined as duration in weeks) to promote adherence to statin medication among those on primary prevention statin treatment by utilizing the modified time-to-event continuous reassessment method (TiTE-CRM). Methods and design The study will utilize the modified TiTE-CRM in 42 participants, recruited in 14 cohorts of 3 participants each. The goal of this analysis is to identify the minimum effective dose (MED) of a multi-behavior change technique (BCT) intervention required to increase adherence to statins by 20% between baseline and follow-up periods. Using the TiTE-CRM method, the dose of the behavior intervention in weeks will be assigned to each cohort based on the performance of the prior cohort. At the end of the study, the intervention dose that has been found to be associated with a 20% increase in statin adherence among 80% of participants assigned to that dose will be identified as the MED. Discussion If successful, the current trial will provide additional guidance to researchers and clinicians seeking to increase statin medication adherence using a BCT intervention by identifying the dose (i.e., the duration) of an intervention required to meaningfully increase adherence. Trial registration ClinicalTrials.gov NCT05273736. Registered on March 10, 2022. https://www.clinicaltrials.gov/ct2/show/NCT05273736

Stress is a significant public health burden in the United States, with most Americans reporting unhealthy levels of stress. Stress management techniques include various evidence-based treatments shown to be effective but with heterogeneous treatment responses, indicating a lack of uniform benefits for all individuals. Designed to assess a participant’s response to a specific intervention, personalized (N-of-1) trials provide guidance for which treatment (s) work (s) best for the individual. Prior studies examining the effects of mindfulness meditation, yoga, and walking for stress reduction found all three interventions to be associated with significant reductions in self-reported measures of stress. Delivering these treatments using a personalized trial approach has the potential to assist clinicians in identifying the best stress management techniques for individuals with persistently high stress while fostering treatment decisions that consider their personal condition/barriers. This trial will evaluate a personalized approach compared to standard of care for three interventions (guided mindfulness meditation; guided yoga; and guided brisk walking) to manage perceived stress. Participants will respond to daily surveys and wear a Fitbit device for 18 weeks. After a 2-week baseline period, participants in the personalized trial groups will receive 12 weeks of interventions in randomized order, while participants in the standard-of-care group will have access to all interventions for self-directed stress management. After intervention, all participants will undergo 2 weeks of observation, followed by two additional weeks of the stress management intervention of their choosing while continuing outcome measurement. At study completion, all participants will be sent a satisfaction survey. The primary analysis will compare perceived stress levels between the personalized and standard of care arms. The results of this trial will provide further support for the use of personalized designs for managing stress.Clinical Trial Registration: clinicaltrials.gov, NCT05408832.Protocol version: 9/14/2022, 21-0968-MRB.

BackgroundFatigue is one of the most common symptoms treated in primary care and can lead to deficits in mental health and functioning. Light therapy can be an effective treatment for symptoms of fatigue; however, the feasibility, scalability, and individual-level heterogeneity of light therapy for fatigue are unknown. ObjectiveThis study aimed to evaluate the feasibility, acceptability, and effectiveness of a series of personalized (N-of-1) interventions for the virtual delivery of bright light (BL) therapy and dim light (DL) therapy versus usual care (UC) treatment for fatigue in 60 participants. MethodsParticipants completed satisfaction surveys comprising the System Usability Scale (SUS) and items assessing satisfaction with the components of the personalized trial. Symptoms of fatigue were measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) daily, PROMIS weekly, and ecological momentary assessment (EMA) questionnaires delivered 3 times daily. Comparisons of fatigue between the BL, DL, and UC treatment periods were conducted using generalized linear mixed model analyses between participants and generalized least squares analyses within individual participants. ResultsParticipants rated the usability of the personalized trial as acceptable (average SUS score=78.9, SD 15.6), and 92% (49/53) of those who completed satisfaction surveys stated that they would recommend the trial to others. The levels of fatigue symptoms measured using the PROMIS daily fatigue measure were lower or improved in the BL (B=−1.63, 95% CI −2.63 to −0.63) and DL (B=−1.44, 95% CI −2.50 to −0.38) periods relative to UC. The treatment effects of BL and DL on the PROMIS daily measure varied among participants. Similar findings were demonstrated for the PROMIS weekly and EMA measures of fatigue symptoms. ConclusionsThe participant scores on the SUS and satisfaction surveys suggest that personalized N-of-1 trials of light therapy for fatigue symptoms are both feasible and acceptable. Both interventions produced significant (P

Purpose: To develop a fully-automatic hybrid algorithm to jointly segment and quantify biomarkers of polypoidal choroidal vasculopathy (PCV) on indocyanine green angiography (ICGA) and spectral domain-OCT (SD-OCT) images. Design: Evaluation of diagnostic test or technology. Participants: Seventy-two participants with PCV enrolled in clinical studies at Singapore National Eye Center. Methods: The dataset consisted of 2-dimensional (2-D) ICGA and 3-dimensional (3-D) SD-OCT images which were spatially registered and manually segmented by clinicians. A deep learning-based hybrid algorithm called PCV-Net was developed for automatic joint segmentation of biomarkers. The PCV-Net consisted of a 2-D segmentation branch for ICGA and 3-D segmentation branch for SD-OCT. We developed fusion attention modules to connect the 2-D and 3-D branches for effective use of the spatial correspondence between the imaging modalities by sharing learned features. We also used self-supervised pretraining and ensembling to further enhance the performance of the algorithm without the need for additional datasets. We compared the proposed PCV-Net to several alternative model variants. Main Outcome Measures: The PCV-Net was evaluated based on the Dice similarity coefficient (DSC) of the segmentations and the Pearson’s correlation and absolute difference of the clinical measurements obtained from the segmentations. Manual grading was used as the gold standard. Results: The PCV-Net showed good performance compared to manual grading and alternative model variants based on both quantitative and qualitative analyses. Compared to the baseline variant, PCV-Net improved the DSC by 0.04 to 0.43 across the different biomarkers, increased the correlations, and decreased the absolute differences of clinical measurements of interest. Specifically, the largest average (mean ± standard error) DSC improvement was for intraretinal fluid, from 0.02 ± 0.00 (baseline variant) to 0.45 ± 0.06 (PCV-Net). In general, improving trends were observed across the model variants as more technical specifications were added, demonstrating the importance of each aspect of the proposed method. Conclusion: The PCV-Net has the potential to aid clinicians in disease assessment and research to improve clinical understanding and management of PCV. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Abstract Background Our aim is to evaluate LI-RADS-TR algorithm and its ability to assess the viability of TACE-treated HCC. We prospectively evaluated 100 patients with known HCC, treated with TACE and came for follow-up to assess therapy response and to plan the next step in treatment using triphasic CT study. Imaging response was evaluated according to LI-RADS-TR algorithm and compared to modified Response Evaluation Criteria in Solid Tumors (mRECIST) arterial phase hyperenhancement (APHE) criterion. Reference standard for “viable” tumors in treated observations included presence of strong tumor hyperenhancement in arterial phase and washout in the delayed phase which also shows dense accumulation of iodized oil in the target lesion. Results When equivocal observations were considered as LR-TR viable, LR-TR viable resulted in 92.31% sensitivity, 83.33% specificity and 88% accuracy. On the other side when equivocal observations were considered as LR-TR nonviable, it resulted in 84.62% while the specificity increased to 100% with increased accuracy (92%). The mRECIST criteria for viable tumors (presence of APHE) showed sensitivity of 84.62% and specificity of 75%. mRECIST and LR-TR sensitivities were the same when equivocal lesions were considered as nonviable and lower mRECIST than LR-TR when equivocal lesions were considered as viable, while specificities were higher in LR-TR viable being 100% when equivocal lesions were considered as nonviable, 83.33% when equivocal lesions were considered as viable and 75% in mRECIST-viable. Conclusions LR-TR algorithm showed good diagnostic performance compared to mRECIST, with high specificity and sensitivity when equivocal lesions were considered as nonviable, as well as improved accuracy.

IntroductionMacrophages are essential immune cells in the cochlea that contribute to inflammation, tissue repair, and homeostasis. They also play an important role in local cochlear immunity. The developmental immigration and maturation of macrophages in the cochlea have been investigated and are considered essential for normal hearing acquisition. Most of our current knowledge regarding cochlear development is based on rodent models because of the ethical challenges of using human fetal samples for research. However, inter-species differences between rodents and humans have been reported. In this study, we used a primate animal model to investigate the distributions of macrophages in the developing cochlea. The common marmoset (Callithrix jacchus), a small monkey species that inhabits the New World, was used as the model.MethodsWe investigated the distribution of macrophages in the developing cochlea of the common marmoset by performing immunohistochemical analyses of cochlear tissue from common marmoset embryos at different development stages.ResultsWe revealed detailed distribution changes in the macrophages of a primate animal model cochlea. This observation indicates that most of the changes in the general distribution of macrophages were well preserved between rodents and this primate. The distribution changes observed in the common marmoset were also compatible with observations in the human fetus; although, observations in the human fetus are limited. Our observations in this study also revealed several differences between common marmosets and rodents.ConclusionThe time course of immunological development and maturations established in this study will aid in the study of the primate-specific developmental biology of the inner ear. These observations may eventually lead to new therapeutic strategies for hearing loss in humans. In addition, understanding the immunological steady-state of the cochlea may help in the study of age- and genetic-induced hearing loss and in the design of regenerative therapies.

The wall paintings from the site of Akrotiri, Thera, are often considered to be instrumental to understanding elements of life in the Bronze Age. This is partially due to their high degree of preservation. The large-scale detail present in the scenes allows for a more detailed and nuanced understanding of the imagery that survives in glyptic art that, considered together with the surviving wall paintings, helps to better inform one’s understanding of Aegean life. Many of the iconographic elements and themes, however, remain at least partially enigmatic. This is particularly the case for Xeste 3, a cultic building at Akortiri, where the wall paintings contribute to a larger, programmatic cultic narrative. The current investigation seeks to better understand the monkeys scene from Room 2 of the first floor by deconstructing and examining each visual element via comparative analyses. They are first contextualized within the Aegean, then considered in light of Mesopotamian comparanda. This method allows for possible parallels between the monkeys from Xeste 3 and at least three priestly classes known from contemporary Mesopotamian tradition: the gala, assinnu, and kurgarrû. Each of these priestly classes belonged to the adaptable and widespread cult of Inanna, one of the most powerful and popular deities in Mesopotamia.

Autophagy can selectively target cargo for degradation. Here the authors map the proximal interactome of ATG8-paralogs LC3B and LC3C uncovering an LC3C-Endocytic-Associated-Pathway that selectively recruits internalized plasma membrane cargo, Met and transferrin receptors, to nascent autophagosomes.

ObjectiveTo identify the determinants of uncontrolled allergic rhinitis (UCAR) in a hospital setting in Kinshasa, Democratic Republic of Congo.MethodsHospital-based cross-sectional study of 153 patients with allergic rhinitis (AR). The diagnosis of AR was based on clinical grounds according to the Allergic Rhinitis and its Impact on Asthma (ARIA) criteria. Categorization into controlled AR (CAR) and UCAR was based on the visual analog scale (VAS with cut off point of 5). Binary logistic regression was used to identify factors associated with UCAR.ResultsPatients with UCAR (60.1%) proportionally outnumbered those with CAR (39.9%). There were significantly more patients younger than 30 years of age among patients with UCAR. Factors significantly associated with UCAR were age below 30 years (OR = 3.31; 95% CI: 1.49–7.36; p = 0.003), low serum vitamin D level (OR = 3.86; 95% CI: 1.72–8.68; p = 0.001), persistent form (OR = 3.11; 95% CI: 1.39–6.98; p = 0.006) and moderate to severe form of AR (OR = 4.31; 95% CI: 1.77–10.49; p = 0.001).ConclusionsFactors associated with UCAR in this study population were younger age less than 30 years, low vitamin D level, and persistent as well as moderate to severe AR. Further studies are needed to elucidate the underlying mechanisms favoring the occurrence of these factors.

Abstract Leucine-rich α-2-glycoprotein 1 (LRG1) is a secreted glycoprotein that under physiological conditions is produced predominantly by the liver. In disease, its local induction promotes pathogenic neovascularisation while its inhibition leads to reduced dysfunctional angiogenesis. Here we examine the role of interleukin-6 (IL-6) in defective angiogenesis mediated by LRG1. IL-6 treatment induced LRG1 expression in endothelial cells and ex vivo angiogenesis cultures and promoted vascular growth with reduced mural cell coverage. In Lrg1 −/− explants, however, IL-6 failed to stimulate angiogenesis and vessels exhibited improved mural cell coverage. IL-6 activated LRG1 transcription through the phosphorylation and binding of STAT3 to a conserved consensus site in the LRG1 promoter, the deletion of which abolished activation. Blocking IL-6 signalling in human lung endothelial cells, using the anti-IL6 receptor antibody Tocilizumab, significantly reduced LRG1 expression. Our data demonstrate that IL-6, through STAT3 phosphorylation, activates LRG1 transcription resulting in vascular destabilisation. This observation is especially timely in light of the potential role of IL-6 in COVID-19 patients with severe pulmonary microvascular complications, where targeting IL-6 has been beneficial. However, our data suggest that a therapy directed towards blocking the downstream angiopathic effector molecule LRG1 may be of greater utility.

Background: Biomarkers to predict the recurrence risk are required to optimize perioperative treatment. Adjuvant chemotherapy for patients with human epidermal growth factor 2-positive (HER2-positive) early breast cancer is decided by pathological responses of neoadjuvant chemotherapy (NAC). However, whether pathological responses are appropriate biomarkers is unclear. Currently, there are several studies using minimal residual disease (MRD) as a predictor of prognosis in solid tumors. However, there is no standard method for detecting MRD. Objectives: This study aimed at prospectively evaluating the relationship between MRD detection and recurrence in Asian patients with HER2-positive early breast cancer. Design: Prospective, observational, single-group, and exploratory. This study will include 60 patients from 2 institutions in Japan and the Philippines. The invasive disease-free survival (IDFS) rates of the MRD-positive and MRD-negative groups are compared in patients with HER2-positive early breast cancer who undergo surgery after receiving NAC. Methods and analysis: Circulating tumor DNA (ctDNA) levels of patients will be evaluated 6 times: before NAC, after NAC, after surgery, and annually after surgery for 3 years. We will analyze the genetic profile of blood and tissue samples using the Todai OncoPanel (TOP) and the methylation level of DNA. The primary endpoint is IDFS. Secondary endpoints include overall survival (OS) and disease-free survival (DFS). Patient enrollment began in June 2022, and new participants are still being recruited. Ethics: This study has been approved by the National Cancer Center Hospital Certified Review Board in March 2022 and has been approved by the Research Ethics Board of the participating center. Discussion: Our findings will contribute to determining whether MRD detection using TOP is useful for predicting the recurrence of HER2-positive early breast cancer. If this is proven, MRD detected by TOP could be used in the future as a biomarker to assist in the de-/escalation of treatment strategies in the next interventional trial, thereby avoiding overtreatment in patients at low risk, and in the addition of intensive treatment modalities for those in patients at high risk. [ABSTRACT FROM AUTHOR]

This study sought to investigate if there was a significant difference between the Huntington's Disease gene expansion carriers who were impaired on the cognitive domains, social cognition and executive functions. Also, it was investigated which of the cognitive domains could predict the decrease in total functional capacity over a 6-year follow-up period. Premanifest and motor-manifest Huntington's Disease gene expansion carriers (N = 98), were examined with a neurological and neuropsychological examination at Time 1 (year 2012–2013). Regression-based normative data was used to classify impairments on the two cognitive domains. Follow-up participants (N = 80) had their functional capacity reexamined at Time 2 (year 2018–2020), to examine which cognitive domain could predict the decrease in functional capacity over the 6-year follow-up. More than 50% of the participants were impaired on the domain of social cognition. These participants were significantly different from the participants who were impaired on executive functions. The motor function and impairments on social cognition significantly predicted the decline in functional capacity. The Emotion Hexagon test was the only significant social cognitive task, that predicted the decline in functional capacity. Social cognition includes unique and separate functions in Huntington's Disease, unaffected by executive functions. This study emphasizes the importance of regular assessment of social cognition in Huntington's Disease and the clinical relevance of impaired social cognitive function. [ABSTRACT FROM AUTHOR]

Abstract Background Healthcare-associated infections (HAI) are one of the gravest threats to patient safety worldwide. The importance of the hospital environment has recently been revalued in infection prevention and control. Though the literature is evolving rapidly, many institutions still do not consider healthcare environmental hygiene (HEH) very important for patient safety. The evidence for interventions in the healthcare environment on patient colonization and HAI with multidrug-resistant microorganisms (MDROs) or other epidemiologically relevant pathogens was reviewed. Methods We performed a systematic review according to the PRISMA guidelines using the PubMed and Web of Science databases. All original studies were eligible if published before December 31, 2019, and if the effect of an HEH intervention on HAI or patient colonization was measured. Studies were not eligible if they were conducted in vitro, did not include patient colonization or HAI as an outcome, were bundled with hand hygiene interventions, included a complete structural rebuild of the healthcare facility or were implemented during an outbreak. The primary outcome was the comparison of the intervention on patient colonization or HAI compared to baseline or control. Interventions were categorized by mechanical, chemical, human factors, or bundles. Study quality was assessed using a specifically-designed tool that considered study design, sample size, control, confounders, and issues with reporting. The effect of HEH interventions on environmental bioburden was studied as a secondary outcome. Findings After deduplication, 952 records were scrutinized, of which 44 were included for full text assessment. A total of 26 articles were included in the review and analyzed. Most studies demonstrated a reduction of patient colonization or HAI, and all that analyzed bioburden demonstrated a reduction following the HEH intervention. Studies tested mechanical interventions (n = 8), chemical interventions (n = 7), human factors interventions (n = 3), and bundled interventions (n = 8). The majority of studies (21/26, 81%) analyzed either S. aureus, C. difficile, and/or vancomycin-resistant enterococci. Most studies (23/26, 88%) reported a decrease of MDRO-colonization or HAI for at least one of the tested organisms, while 58% reported a significant decrease of MDRO-colonization or HAI for all tested microorganisms. Forty-two percent were of good quality according to the scoring system. The majority (21/26, 81%) of study interventions were recommended for application by the authors. Studies were often not powered adequately to measure statistically significant reductions. Interpretation Improving HEH helps keep patients safe. Most studies demonstrated that interventions in the hospital environment were related with lower HAI and/or patient colonization. Most of the studies were not of high quality; additional adequately-powered, high-quality studies are needed. Systematic registration number: CRD42020204909

Abstract The aim of this study was to evaluate influence of baseline imaging features on visual and anatomical outcomes in eyes with PCV treated with anti-VEGF monotherapy. In this prospective study we enrolled participants with treatment-naïve PCV who followed a treat-and-extend protocol using intravitreal aflibercept (IVA) monotherapy. Baseline clinical features evaluatedincluded best corrected visual acuity (BCVA), traditional features such as lesion size, fluid-related OCT parameters and novel parameters using automated software. This included quantitative and qualitative pigment epithelium detachment (PED) parameters [height, volume]; and choroidal parameters. [choroidal thickness (CT), choroidal volume (CV) and choroidal vascularity index (CVI). We evaluated the predictive value of each parameter on visual and anatomical outcome at month 12. We additionally evaluated initial treatment response after 3 monthly injections with respect to month 12 outcomes. Fifty-two eyes from 52 participants were included in the study. The BCVA increased from 61.1 ± 13.2 to 69.6 ± 13.2 early treatment diabetic retinopathy study (ETDRS) letters (p

Purpose – The main objective of this project was to evaluate typhoon-related Tweets’ urgency using sentiment analysis with supervised learning over an artificial neural network. Method – The researchers implemented artificial neural network and natural language processing techniques for sentiment analysis and evaluation of the urgency score of typhoon-related Tweets. The model’s accuracy on training and validation was evaluated simultaneously. A separate validation using 100 data was done using confusion matrix analysis. Results – The accuracy of the model in training was at 99.87% and the loss was 0.0074. Validation was conducted simultaneously with the training. It was found that the accuracy of the model was at 99.17% and the loss was 0.0680. The confusion matrix analysis showed that the sensitivity was 97.67% and the specificity was 100%. The positive predictive value was 100% and the negative predicted value was 98.28%. Both false positive and false discovery rates are at 0% while the false-negative rate was at 2.33%. Finally, the F1 score was 98.82% and accuracy was 99%. Conclusion – The implementation of the architecture of the model was successful; the researchers concluded that the training produced successful results by looking at the high accuracy prediction of the model and the low loss during the simultaneous training and validation, and confusion matrix analysis for the separate validation. Recommendations – The researchers recommend expanding the vocabulary of the model by adding more diverse data to the dataset when training. The model produced by this study can be used in incident reporting systems that will be helpful during times of typhoon-related disasters. Research Implications – Using the model produced by the study in incident reporting applications of the government and NGOs will be more efficient than manually looking at typhoon-related posts on Twitter.

Summary: BK polyomavirus (BKPyV) is an opportunistic pathogen that uses the b-series gangliosides GD1b and GT1b as entry receptors. Here, we characterize the impact of naturally occurring VP1 mutations on ganglioside binding, VP1 protein structure, and virus tropism. Infectious entry of single mutants E73Q and E73A and the triple mutant A72V-E73Q-E82Q (VQQ) remains sialic acid dependent, and all three variants acquire binding to a-series gangliosides, including GD1a. However, the E73A and VQQ variants lose the ability to infect ganglioside-complemented cells, and this correlates with a clear shift of the BC2 loop in the crystal structures of E73A and VQQ. On the other hand, the K69N mutation in the K69N-E82Q variant leads to a steric clash that precludes sialic acid binding. Nevertheless, this mutant retains significant infectivity in 293TT cells, which is not dependent on heparan sulfate proteoglycans, implying that an unknown sialic acid-independent entry receptor for BKPyV exists.

Climate change is altering patterns of temporal co-occurrence among species, such as the degree of co-flowering among plant species. Although much is known about how co-flowering affects pollination and plant reproduction, how these interactions are mediated by changes in abiotic conditions is unclear. Using a short-term field experiment based on a long-term flowering phenology dataset, we examine how changes in co-flowering between Linum lewisii and Potentilla pulcherrima affect the pollination and reproductive success of Linum in control and water addition scenarios. Linum is co-flowering less than it used to with Potentilla as the climate changes. We therefore removed Potentilla flowers to alter the degree of co-flowering from 0 to 100%; half of these plots received additional water to relieve drought stress. Linum plants experiencing less overlap with Potentilla had a higher proportion of conspecific pollen on their stigmas in both watered and unwatered plots. Plants experiencing less overlap also produced more seeds per plant, but only in the watering treatment. There was no evidence of pollen limitation of reproduction, but watered plants produced more seeds. These results show that plants that co-flowered to a lesser extent with Potentilla had enhanced reproductive output, probably because they received a higher proportion of Linum pollen, but these biotic effects were only detectable when the plants were less water-limited. This study provides empirical evidence that climate-driven changes in co-flowering can alter reproduction via competition for pollination, and that these biotic effects can be mediated by abiotic conditions.

Several factors contribute to the development of breast cancer, including the immune system. This study is aimed to characterize the carriage of human leukocyte antigen (HLA)-DRB1*11 and 1*12 alleles in patients with breast cancer. This case-control study consisted of 96 histologically diagnosed breast cancer cases and 102 controls (cases without breast abnormalities). A multiplex polymerase chain reaction (PCR) was used to characterize the carriage of HLA-DRB1*11 and 1*12 alleles. The HLA-DRB1*11 allele was present in 26.59% of cases and 22.55% of controls. The HLA-DRB1*12 allele was present in 56.63% of cases and 55.88% of controls. This study found no direct association between the carriage of the HLA-DRB1*11 and HLA-DRB1*12 alleles and the occurrence of breast cancer. In addition, the deletion of the HLA-DRB1*11 allele is associated (beneficial effect) with obesity/overweight (OR = 0.13; 95% CI [0.01–1.14]; and p = 0.03) which is a risk for breast cancer. No direct association was found between the carriage of HLA-DRB1*11 and 1*12 alleles and breast cancer risk. However, further investigation of other HLA alleles involved in the occurrence of breast cancer may provide more information.