Search

The coronavirus disease 2019 (COVID-19) pandemic prompted tens of thousands of people worldwide to migrate from cities in its early stages, leading to an increased spread of the virus. Understanding the factors driving relocation during a pandemic is crucial for effective outbreak control. We investigated how the pandemic influenced people’s aspirations and preparations to move, both domestically and internationally, surveying individuals in Greece, India, Italy, Kenya, Nigeria, Portugal, Serbia, Spain, and the United States of America. Out of 4448 eligible responses, 765 participants (17.2%) had a strong aspiration to move due to COVID-19, and 155 (3.5%) had already prepared. Those considering relocation were statistically significantly more likely to perceive moving to an area with fewer COVID-19 cases as protective against the virus (OR = 1.3, p < 0.05) or to know others who intended to relocate because of COVID-19 (OR = 1.5, p < 0.05). Conversely, a strong sense of being ‘at home’ reduced statistically significantly the strength of mobility aspirations (OR = 0.7, p < 0.01). Social alienation, social imitation, and the perceived efficacy of mobility increased aspirations to move due to COVID-19. This study emphasizes the rapid population movements at pandemic onset and their potential contribution to disease transmission, urging future pandemic planning to take account of such mobility dynamics.

Mucormycosis, an invasive fungal infection caused by members of the order Mucorales, often progresses fulminantly if not recognized in a timely manner. This comprehensive review discusses the latest developments in diagnostic approaches for mucormycosis, from traditional histopathology and culture-based methods to advanced and emerging techniques such as molecular assays, imaging, serology, and metabolomics. We discuss challenges in the diagnosis of mucormycosis and emphasize the importance of rapid and accurate identification of this life-threatening infection.

As adiposity increases in youth, so does the prevalence of cardiometabolic risk factors (CMRFs). The etiology of adiposity-based chronic disease and CMRFs includes ethnoracial disparities that are rarely considered in current treatment approaches. Precision interventions require further characterization of these disparities among high-risk youth. The objective of this study was to characterize differences in CMRF among African American (AA) and Hispanic (H) adolescents with varying levels of adiposity. A cross-sectional analysis of 2284 adolescents aged 12–17 was conducted using 3-year clinical data from Lifedoc Health. CMRF prevalence were compared using χ2, with logistic regression models (LRM) applied to explore the relationships between exposures (age, sex, ethnoracial group, adiposity) and CMRF outcomes. Prevalence of CMRF rose with increasing adiposity, which was the strongest determinant of risk overall. However, individual risk profiles differed between the two groups, with H having higher prevalence of metabolic syndrome (MetS), higher triglycerides and liver enzymes, and low high-density lipoprotein cholesterol (HDL-c). Meanwhile, AA had higher prevalence of elevated blood pressure (BP) in the overweight category, prediabetes in overweight to severe obesity, and type 2 diabetes in obesity. LRM showed 3.0-fold greater chance of impaired glucose metabolism in AA than H, who were 1.7, 5.9, and 8.3 times more likely to have low HDL-c, high liver enzymes, and high triglycerides, respectively. Overweight/obesity prevalence was very high among AA and H adolescents. Excess adiposity was associated with an increased prevalence of CMRF, with individual risk factors differing between groups as adiposity increased. Research within routine clinical settings is required to better characterize these discrepancies and ameliorate their adverse impact on health in the transition to adulthood.

Emerging evidence in women supports the notion that pregnancy may reset disease resistance, thereby providing protection against subsequent adverse health outcomes, but this hypothesis has not been adequately explored in domestic dogs. Cranial cruciate ligament (CCL) rupture is a degenerative orthopedic disease that frequently affects pet dogs, and its risk has been associated with disruption of the reproductive hormone axis. Our research team is conducting a lifetime cohort study of purebred Rottweilers in North America that have lived 30% longer than breed-average. Detailed medical and reproductive histories of 33 nulliparous and 32 parous Rottweilers were generated from questionnaires and review of medical records. Interviews with owners of bitches in the nulliparous group served to limit selection bias, confirming that in no instance was the reason for nulliparity based upon the owner’s suspicion that a bitch had a heightened risk for CCL rupture. The risk of CCL rupture associated with parity and other exposure variables was estimated using multivariate logistic regression. Overall, CCL rupture was diagnosed in 17 of 65 (26%) bitches. Median age at first litter and CCL rupture were 3.6 and 6.5 years, respectively. Compared to nulliparous, parous bitches had a significant 94% reduction in CCL rupture risk adjusted for duration of ovary exposure, overweight body condition, dietary pattern, habitual physical activity, and work/sport activity [ORadjusted (95% CI) = 0.06 (0.01–0.46); (p = 0.006)]. The observed parity-associated CCL rupture risk reduction remained robust in sensitivity analysis excluding six nulliparous bitches for which decision not to breed was based on diagnosis of hip or elbow dysplasia, conditions which may be genetically linked to CCL rupture [ORadjusted (95% CI) = 0.08 (0.01–0.58); (p = 0.01)]. This work sets the stage for replication studies in other canine populations that should begin to explore the mechanistic basis for parity-associated CCL rupture risk reduction and to pursue other non-reproductive health outcomes in bitches whose incidence or severity may be parity-sensitive.

Abstract Cranial cruciate ligament (CCL) rupture is one of the most commonly diagnosed orthopedic conditions of pet dogs, making estimated lifetime cruciate ligament survival an attractive endpoint for studies attempting to define clinical and genetic correlates of rupture risk reduction. Early life experiences contribute significantly to the origins of adult health outcomes, yet our current understanding of modifiable susceptibility factors that drive the high frequency of CCL rupture remains limited. We reasoned that combining lifetime medical history with standardized late-life assessment of lifetime cruciate ligament survival and detailed phenotyping of each dog for selected risk variables would provide a sensitive approach to identify factors that would differentiate between lifelong avoidance versus susceptibility to ligament rupture. Here, we report results of Kaplan–Meier analysis of estimated lifetime cruciate ligament survival and Cox proportional hazards modeling to assess risk variables in a lifetime cohort study of 123 purebred Rottweilers, a breed at high risk for veterinarian-diagnosed CCL rupture. We show that gonad removal during the 24-month developmental period is adversely associated with three measures of susceptibility—increased incidence of CCL rupture, multiplicity (bilateral rupture), and accelerated time to initial CCL failure. Our analysis reveals two other phenotypes—short adult height and the production of offspring (in females)—are associated with significant CCL rupture risk reduction. Together, the results provide clues to an early endocrine influence on lifetime cruciate ligament survival. Further, we identify two distinct clinical syndromes of CCL failure, providing a disease subtyping framework to advance future progress in genetic epidemiology, pathogenesis, and prediction. By conducting an evaluation of estimated lifetime CCL survival in dogs, we show that cruciate ligament survival may be jeopardized by gonad removal during the developmental period. Avoidance of such early environmental adversity may represent an actionable method for the control of canine CCL disease in certain breeds.

Objective The objective of this cross‐sectional study was to investigate the impact of the COVID‐19 pandemic on physical activity (PA) levels of patients with rheumatic and musculoskeletal diseases (RMDs) and to examine factors associated with decreased PA. Methods A sample of adult patients with RMDs (n = 7,776) was identified through electronic medical records from an academic health care system in North Carolina. Invitations to participate in an online survey were sent between July 2020 and September 2020 to assess self‐reported changes in PA during the COVID‐19 pandemic. Descriptive statistics, age‐adjusted prevalence odds ratios (PORs), and 95% confidence intervals (CIs) were computed to examine patient characteristics associated with decreased PA. Results A total of 893 eligible participants completed the survey (mean age 57.8 ± 14.9 years, 75.8% female). The most common primary diagnoses reported among participants included rheumatoid arthritis (27.3%), osteoarthritis (16.0%), and systemic lupus erythematosus (SLE) (13.0%). More than half of participants (56.8%) reported engaging in less PA since the pandemic began. Factors associated with engaging in less PA included lower self‐reported general health (POR, 2.21; CI, 1.64‐2.97) and a diagnosis of SLE (POR, 1.57; CI, 1.03‐2.38). Comorbidities associated with decreased PA included chronic pain (POR, 1.38; CI, 1.04‐1.82), depression (POR, 1.48; CI, 1.09‐2.01), and hypertension (POR, 1.44; CI, 1.10‐1.90). Conclusion The COVID‐19 pandemic has exacerbated barriers to PA in patients with RMDs. There is a critical need to provide resources, support, and multifaceted programs to encourage PA in patients with RMDs during the COVID‐19 pandemic.

Neurodegenerative diseases, tauopathies, constitute a serious global health problem. The etiology of these diseases is unclear and an increase in their incidence has been projected in the next 30 years. Therefore, the study of the molecular mechanisms that might stop these neurodegenerative processes is very relevant. Classification of neurodegenerative diseases using Machine and Deep Learning algorithms has been widely studied for medical imaging such as Magnetic Resonance Imaging. However, post-mortem immunofluorescence imaging studies of the brains of patients have not yet been used for this purpose. These studies may represent a valuable tool for monitoring aberrant chemical changes or pathological post-translational modifications of the Tau polypeptide. We propose a Convolutional Neural Network pipeline for the classification of Tau pathology of Alzheimer’s disease and Progressive Supranuclear Palsy by analyzing post-mortem immunofluorescence images with different Tau biomarkers performed with models generated with the architecture ResNet-IFT using Transfer Learning. These models’ outputs were interpreted with interpretability algorithms such as Guided Grad-CAM and Occlusion Analysis. To determine the best classifier, four different architectures were tested. We demonstrated that our design was able to classify diseases with an accuracy of 98.41% on average whilst providing an interpretation concerning the proper classification involving different structural patterns in the immunoreactivity of the Tau protein in NFTs present in the brains of patients with Progressive Supranuclear Palsy and Alzheimer’s disease.

Obesity is defined as excess adipose tissue; however, commonly used methods may under-detect adiposity in adolescents. This study compared the performance of body mass index percentile (BMI%) and relative body mass index (RBMI) in identifying excess body fat percentage (BF%) and estimated RBMI cut points to better stratify severity of adiposity. In 567 adolescents ages 11–19 year, BF% measured by DXA was used to compare BMI% and RBMI performance at different degrees of adiposity. RBMI cut points for adiposity detection were derived via ROC curve analysis. BF% was strongly correlated with BMI% (r = 0.889, p < 0.001) and RBMI (r = 0.901, p < 0.001). However, RBMI exhibited less dispersion and better discriminated the relationship with BF% independent of age, race, and gender. Both BMI% and RBMI performed similarly for detecting high BF% (≥25 BF% in males; ≥30 BF% in females). Nonetheless, the relationship of BMI% with BF% was diminished among leaner adolescents. RBMI detected overweight in 21.3% more females and 14.2% more males. RBMI improved the detection of excess adiposity in individuals otherwise classified as having normal weight or overweight by BMI%. RBMI is a valuable and accessible tool for earlier detection, intervention, and effective follow-up of excess adiposity in youth at higher risk for complications.

Drilled shafts are cylindrical, cast-in-place concrete deep foundation elements. During construction, anomalies in drilled shafts can occur due to the kinematics of concrete, flowing radially from the center of the shaft to the concrete cover region at the peripheral edge. This radial component of concrete flow develops veins or creases of poorly cemented or high water-cement ratio material, as the concrete flows around the reinforcement cage of rebars and ties, jeopardizing the shaft integrity. This manuscript presents a three-dimensional computational fluid dynamics (CFD) model of the non-Newtonian concrete flow in drilled shaft construction developed using the finite volume method with interface tracking based on the volume of fluid (VOF) method. The non-Newtonian behavior of the concrete is represented via the Carreau constitutive model. The model results are encouraging as the flow obtained from the simulations shows patterns of both horizontal and vertical creases in the concrete cover region, consistent with previously reported field and laboratory experiments. Moreover, the flow exhibits the concrete head differential developed between the inside and the outside of the reinforcement cage, as exhibited in the physical experiments. This head differential induces the radial component of the concrete flow responsible for the creases that develop in the concrete cover region. Results show that the head differential depends on the flowability of the concrete, consistent with field observations. Less viscous concrete tends to reduce the head differential and the formation of creases of poorly cemented material. The model is unique, making use of state-of-the-art numerical techniques and demonstrating the capability of CFD to model industrially relevant concrete flows.

The quality and quantity of the food we consume have a major impact on our general health and longevity [...]

BackgroundThe global prevalence of PASC is estimated to be present in 0·43 and based on the WHO estimation of 470 million worldwide COVID-19 infections, corresponds to around 200 million people experiencing long COVID symptoms. Despite this, its clinical features are not well-defined.MethodsWe collected retrospective data from 140 patients with PASC in a post-COVID-19 clinic on demographics, risk factors, illness severity (graded as one-mild to five-severe), functional status, and 29 symptoms and principal component symptoms cluster analysis. The Institute of Medicine (IOM) 2015 criteria were used to determine the Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) phenotype.FindingsThe median age was 47 years, 59.0% were female; 49.3% White, 17.2% Hispanic, 14.9% Asian, and 6.7% Black. Only 12.7% required hospitalization. Seventy-two (53.5%) patients had no known comorbid conditions. Forty-five (33.9%) were significantly debilitated. The median duration of symptoms was 285.5 days, and the number of symptoms was 12. The most common symptoms were fatigue (86.5%), post-exertional malaise (82.8%), brain fog (81.2%), unrefreshing sleep (76.7%), and lethargy (74.6%). Forty-three percent fit the criteria for ME/CFS, majority were female, and obesity (BMI > 30 Kg/m2) (P = 0.00377895) and worse functional status (P = 0.0110474) were significantly associated with ME/CFS.InterpretationsMost PASC patients evaluated at our clinic had no comorbid condition and were not hospitalized for acute COVID-19. One-third of patients experienced a severe decline in their functional status. About 43% had the ME/CFS subtype.

The lissencephaly 1 protein, LIS1, is mutated in type-1 lissencephaly and is a key regulator of cytoplasmic dynein-1. At a molecular level, current models propose that LIS1 activates dynein by relieving its autoinhibited form. Previously we reported a 3.1 Å structure of yeast dynein bound to Pac1, the yeast homologue of LIS1, which revealed the details of their interactions (Gillies et al., 2022). Based on this structure, we made mutations that disrupted these interactions and showed that they were required for dynein’s function in vivo in yeast. We also used our yeast dynein-Pac1 structure to design mutations in human dynein to probe the role of LIS1 in promoting the assembly of active dynein complexes. These mutations had relatively mild effects on dynein activation, suggesting that there may be differences in how dynein and Pac1/LIS1 interact between yeast and humans. Here, we report cryo-EM structures of human dynein-LIS1 complexes. Our new structures reveal the differences between the yeast and human systems, provide a blueprint to disrupt the human dynein-LIS1 interactions more accurately, and map type-1 lissencephaly disease mutations, as well as mutations in dynein linked to malformations of cortical development/intellectual disability, in the context of the dynein-LIS1 complex.

Recently, there has been a growing interest in two-dimensional van der Waals (vdW) magnets owing to their unique two-dimensional magnetic phenomena and potential applications. Most vdW ferromagnets have the Curie temperature below room temperature, highlighting the need to explore how to enhance their magnetism. In our previous report, we successfully increased the Curie temperature of the prototypical vdW magnet Cr2Ge2Te6 using a NiO overlayer. In layered materials, the presence of wrinkles is often observed and evaluating them using optical microscopy proves to be useful; however, there have been limited investigations into the optical constants of vdW magnets, hampering progress in understanding their optical properties. In this study, we present the optical constants of Cr2Ge2Te6 obtained through ellipsometry measurements. To account for the presence of wrinkles, we model a vacuum region between the substrate and the vdW magnet, and we calculate the reflectivity as a function of wavelength and vacuum thickness to visualize the optical image. Furthermore, we discuss the relationship between the optical constants and the electronic structure of the material.

Primary structure endows tertiary structure while tertiary structure determines function. This fundamental principle is responsible for the generation of high order and precise functions in both biological assemblies including giant and mega proteins and nucleic acids as well as in metals generated from only few atoms. However, this size-independent ability to generate high order and very precise functions is not yet accessible in non-biological assemblies that use the same principles for their hierarchical self-organization. Here we report a study investigating the role of the molecular parameters on the hierarchical self-organizations of helical columnar assemblies produced from the column-forming self-assembling dendron (4-3,4-3,5)-X with a linear or branched hydrogenated or linear semifluorinated alkyl groups while apex is -CO2CH3 or -CH2OH. A combination of differential scanning calorimetry, small and wide-angle powder and oriented fiber X-ray diffraction experiments together with helical diffraction theory, 2-D and 3-D electron density maps were employed in these structural analysis experiments. They demonstrated that H-bonding at the apex of the self-assembling dendron enhanced the order of the helical columns by comparison with the order of supramolecular helical columns based on dendrons containing an ester group at their apex. This was the case for both linear and branched alkyl groups at the periphery of the self-assembling dendron. Unexpectedly, self-assembling dendrons containing semifluorinated alkyl groups on their periphery and H-bonding groups at their apex increase even more the order of their supramolecular perfluorinated porous helical column. In all cases helix is mediated by the aromatic part of the dendron but hierarchically influenced both by the apex and peripheral groups. A combination of branched alkyl groups with H-bonding at the apex produced a new mechanism to transform helical columns assembled from the column-forming (4-3,4-3,5)-X self-assembling dendron into spherical assemblies, organized from conical dendron conformers, forming an A15 Frank-Kasper phase.

Haptic perception is a vital part of the human experience that enriches our engagement with the world, but the ability to provide haptic information in virtual reality (VR) environments is limited. Neurostimulation-based sensory feedback has the potential to enhance the immersive experience within VR environments by supplying relevant and intuitive haptic feedback related to interactions with virtual objects. Such feedback may contribute to an increase in the sense of presence and realism in VR and may contribute to the improvement of virtual reality simulations for future VR applications. This work developed and evaluated xTouch, a neuro-haptic platform that extends the sense of touch to virtual environments. xTouch is capable of tracking a user’s grasp and manipulation interactions with virtual objects and delivering haptic feedback based on the resulting grasp forces. Seven study participants received haptic feedback delivered via multi-channel transcutaneous electrical stimulation of the median nerve at the wrist to receive the haptic feedback. xTouch delivered different percept intensity profiles designed to emulate grasp forces during manipulation of objects of different sizes and compliance. The results of a virtual object classification task showed that the participants were able to use the active haptic feedback to discriminate the size and compliance of six virtual objects with success rates significantly better than the chance of guessing it correctly (63.9 ± 11.5%, chance = 16.7%, p < 0.001). We demonstrate that the platform can reliably convey interpretable information about the physical characteristics of virtual objects without the use of hand-mounted devices that would restrict finger mobility. Thus, by offering an immersive virtual experience, xTouch may facilitate a greater sense of belonging in virtual worlds.

Abstract The dense Miocene record of cetaceans is known from localities along the coasts of all continents, mostly in the northern Atlantic or the eastern Pacific regions, but Antarctica. Fossils from the Caribbean region are few and include of a couple of findings from Panama and Venezuela. Here, we report a partly complete skull from the Caujarao Formation (middle Miocene), Falcon State, Caribbean region of Venezuela. Our phylogenetic analyses indicate that the Caujarao specimen is a ‘stem delphinidan’, a group that includes several taxa of early diverging odontocetes whose phylogenetic affinities remain a matter of debate. The fossil record has shown that this group of stem delphinidans was taxonomically diverse, but displayed a somewhat homogeneous cranial patterning, with most of the variations being found within the mandible or tympanoperiotic characters. As other stem delphinidans the Caujarao odontocete displays an enlarged temporal fossa and a fairly symmetrical cranium. Because the skull is missing several key diagnostic characters due to the preservation state of the specimen, a more precise taxonomic identification is not possible. Despite this, the finding of this specimen highlights the importance of the fossil record from the Neogene of Venezuela, and the importance of the area to understand cetacean evolution in the proto-Caribbean.

Purpose: To report a case of severe mpox in a newly diagnosed HIV patient concerning for Immune Reconstitution Inflammatory Syndrome (IRIS) and/or tecovirimat resistance and to describe the management approach in the setting of refractory disease. Case: 49-year-old man presented with 2 weeks of perianal lesions. He tested positive for mpox PCR in the emergency room and was discharged home with quarantine instructions. Three weeks later, the patient returned with disseminated firm, nodular lesions in the face, neck, scalp, mouth, chest, back, legs, arms, and rectum, with worsening pain and purulent drainage from the rectum. The patient reported being on 3 days of tecovirimat treatment, which was prescribed by the Florida department of health (DOH). During this admission, he was found to be HIV positive. A pelvic CT scan revealed a 2.5 cm perirectal abscess. Treatment with tecovirimat was continued for 14 days, along with an empiric course of antibiotics for treatment of possible superimposed bacterial infection upon discharge. He was seen in the outpatient clinic and initiated antiretroviral therapy (ART) with TAF/emtricitabine/bictegravir. Two weeks after starting ART, the patient was readmitted for worsening mpox rash and rectal pain. Urine PCR also returned positive for chlamydia, for which the patient was prescribed doxycycline. He was discharged on a second course of tecovirimat and antibiotic therapy. Ten days later, the patient was readmitted for the second time due to worsening symptoms and blockage of the nasal airway from progressing lesions. At this point, there were concerns for tecovirimat resistance, and after discussion with CDC, tecovirimat was reinitiated for the third time, with the addition of Cidofovir and Vaccinia, and showed an improvement in his symptoms. He received three doses of cidofovir and two doses of Vaccinia, and the patient was then discharged to complete 30 days of tecovirimat. Outpatient follow-up showed favorable outcomes and near resolution. Conclusion: We reported a challenging case of worsening mpox after Tecovirimat treatment in the setting of new HIV and ART initiation concerning IRIS vs. Tecovirimat resistance. Clinicians should consider the risk of IRIS and weigh the pros and cons of initiating or delaying ART. In patients not responding to first-line treatment with tecovirimat, resistance testing should be performed, and alternative options should be considered. Future research is needed to establish guidance on the role of Cidofovir and Vaccinia immune globulin and the continuation of tecovirimat for refractory mpox.

Clustering is an unsupervised learning technique used in data mining for finding groups with increased object similarity within but not between them. However, the absence of a-priori knowledge on the optimal clustering criterion, and the strong bias of traditional algorithms towards clusters with a specific shape, size, or density, raise the need for more flexible solutions to find the underlying structures of the data. As a solution, clustering has been modeled as an optimization problem using meta-heuristics for generating a search space to favor groups of any desired criterion. F1- ECAC is an evolutionary clustering algorithm with an objective function designed as a supervised learning problem, which evaluates the quality of a partition in terms of its generalization degree, or its capability to train an ensemble of classifiers. This algorithm is named after its previous version, ECAC (Evolutionary Clustering Algorithm Using Supervised Classifiers), considering its main point of difference, which is the inclusion of the F1-score instead of the Area Under the Curve metric in the objective function. F1- ECAC shows a significant increase in performance and efficiency to ECAC and is highly competitive to state-of-the-art clustering algorithms. The results demonstrate F1-ECAC’s benefits in usability in a wide variety of problems due to its innovative clustering criterion.

Abstract The Cullin 5 (CUL5) Ring E3 ligase uses adaptors Elongins B and C (ELOB/C) to bind different SOCS-box-containing substrate receptors, determining the substrate specificity of the ligase. The 18-member ankyrin and SOCS box (ASB) family is the largest substrate receptor family. Here we report cryo-EM data for the substrate, creatine kinase (CKB) bound to ASB9-ELOB/C, and for full-length CUL5 bound to the RING protein, RBX2, which binds various E2s. To date, no full structures are available either for a substrate-bound ASB nor for CUL5. Hydrogen–deuterium exchange (HDX-MS) mapped onto a full structural model of the ligase revealed long-range allostery extending from the substrate through CUL5. We propose a revised allosteric mechanism for how CUL-E3 ligases function. ASB9 and CUL5 behave as rigid rods, connected through a hinge provided by ELOB/C transmitting long-range allosteric crosstalk from the substrate through CUL5 to the RBX2 flexible linker.

Purpose. To analyze the perspectives of practicing refractive surgeons regarding the implementation of Immediate Sequential Bilateral Cataract Surgery (ISBCS) in the United States (US) and to compare their perspectives with those of European colleagues. Setting. Online refractive surgery forum. Design. A survey-based questionnaire. Methods. An electronic survey was emailed to all surgeon members of the Refractive Surgery Alliance (RSA) in the US. Participants were prompted to score their impressions regarding various aspects regarding ISBCS. Responses were compared to published reports conducted among European surgeons. Results. The electronic link to the survey was emailed to US-based surgeon members of the RSA, where 107 participated (44.6%). Twenty-seven (25.2%) reported that they currently perform ISBCS. Twenty-three (22.5%) of the respondents indicated they felt ISCBCS should be offered as a standard of care for routine cataract surgery. For surgeons that do not perform ISBCS, the most important factors were related to medicolegal issues and decreased reimbursement, whereas evidence of effectiveness and complications related to ISBCS were less important. Compared to practitioners abroad, 67.2% of European ophthalmic surgeons, compared to 25.2% of US surgeons, perform ISBCS (p

The lissencephaly 1 gene, LIS1, is mutated in patients with the neurodevelopmental disease lissencephaly. The Lis1 protein is conserved from fungi to mammals and is a key regulator of cytoplasmic dynein-1, the major minus-end-directed microtubule motor in many eukaryotes. Lis1 is the only dynein regulator known to bind directly to dynein’s motor domain, and by doing so alters dynein’s mechanochemistry. Lis1 is required for the formation of fully active dynein complexes, which also contain essential cofactors: dynactin and an activating adaptor. Here, we report the first high-resolution structure of the yeast dynein–Lis1 complex. Our 3.1 Å structure reveals, in molecular detail, the major contacts between dynein and Lis1 and between Lis1’s ß-propellers. Structure-guided mutations in Lis1 and dynein show that these contacts are required for Lis1’s ability to form fully active human dynein complexes and to regulate yeast dynein’s mechanochemistry and in vivo function.

a previsão de demanda é uma metodologia da administração de empresas para estimar um valor futuro de uma grandeza de interesse. Realizar previsões de demanda significa reconhecer padrões de comportamento em séries históricas e predizer o comportamento futuro ou, ainda, identificar fatores causais que afetam o comportamento e extrapolá-lo. Este artigo tem por objetivo realizar uma revisão da literatura dos métodos de previsão de demanda com o propósito de reunir os métodos e os modelos disponíveis acerca dos conceitos utilizados atualmente na administração de empresas relacionados ao consumo e à produção de produtos e serviços. A metodologia utilizada é a revisão da literatura com abordagem qualitativa, com o propósito de dar uma visão descritiva geral dos métodos dominantes utilizados em previsão de demanda. Foi realizado o mapeamento da literatura para identificar o estado da ciência por meio da produção científica disponível nos bancos de dados Scopus e Google Scholar. Os métodos qualitativos e os causais estão mais bem associados a previsões de médio e longo prazos. A análise de séries temporais bem como os métodos dos diversos tipos de médias e de suavização exponencial são indicados como os mais adequados para previsões de curto prazo. Um recurso utilizado em diversas realidades é a construção de um modelo próprio de previsão de demanda, o qual utilize técnicas, aspectos, conceitos e características de diferentes métodos e modelos. É fundamental monitorar o modelo adotado, manter os dados de campo e de previsão sob controle e, se houver desvios, corrigir o modelo.

This paper presents an integrated monitoring system for the driver and the vehicle in a single case of study easy to configure and replicate. On-board vehicle sensors and remote sensors are combined to model algorithms for estimating polluting emissions, fuel consumption, driving style and driver’s health. The main contribution of this paper is the analysis of interactions among the above monitored features highlighting the influence of the driver in the vehicle performance and vice versa. This analysis was carried out experimentally using one vehicle with different drivers and routes and implemented on a mobile application. Compared to commercial driver and vehicle monitoring systems, this approach is not customized, uses classical sensor measurements, and is based on simple algorithms that have been already proven but not in an interactive environment with other algorithms. In the procedure design of this global vehicle and driver monitoring system, a principal component analysis was carried out to reduce the variables used in the training/testing algorithms with objective to decrease the transfer data via Bluetooth between the used devices: a biometric wristband, a smartphone and the vehicle’s central computer. Experimental results show that the proposed vehicle and driver monitoring system predicts correctly the fuel consumption index in 84%, the polluting emissions 89%, and the driving style 89%. Indeed, interesting correlation results between the driver’s heart condition and vehicular traffic have been found in this analysis.

Introduction and objectives: Failures at any step in the hepatocellular carcinoma (HCC) surveillance process can result in HCC diagnostic delays and associated worse prognosis. We aimed to estimate the prevalence of surveillance failure and its associated risk factors in patients with HCC in Argentina, considering three steps: 1) recognition of at-risk patients, 2) implementation of HCC surveillance, 3) success of HCC surveillance. Methods: We performed a multi-center cross-sectional study of patients at-risk for HCC in Argentina seen between10.01.2018 and 10.30.2019. Multivariable logistic regression analysis was used to identify correlates of surveillance failure. Results: Of 301 included patients, the majority were male (74.8%) with a mean age of 64 years old. At the time of HCC diagnosis, 75 (25%) patients were unaware of their diagnosis of chronic liver disease, and only 130 (43%) patients were under HCC surveillance. Receipt of HCC surveillance was significantly associated with follow-up by a hepatologist. Of 119 patients with complete surveillance, surveillance failure occurred in 30 (25%) patients. Surveillance failure was significantly associated with alpha fetoprotein ≥20 ng/mL (OR 4.0, CI 95% 1.43−11.55). Conclusions: HCC surveillance failure was frequent in all the evaluated steps. These data should help guide strategies to improve the implementation and results of HCC surveillance in our country.

Introduction: Failures at any step in the hepatocellular carcinoma (HCC) surveillance process can result in HCC diagnostic delays and associated worse prognosis. Objectives: We aimed to estimate the prevalence of surveillance failure and its associated risk factors in patients with HCC in Argentina, considering three steps: 1) recognition of at-risk patients, 2) implementation of HCC surveillance, 3) success of HCC surveillance. Methods: We performed a multi-center cross-sectional study of patients at-risk for HCC in Argentina seen between10.01.2018 and 10.30.2019. Multivariable logistic regression analysis was used to identify correlates of surveillance failure. Results: Of 301 included patients, the majority were male (74.8%) with a mean age of 64 years old. At the time of HCC diagnosis, 75 (24.9%) patients were unaware of their diagnosis of chronic liver disease, and only 130 (43.2%) patients were under HCC surveillance. Receipt of HCC surveillance was significantly associated with follow-up by a hepatologist. Of 119 patients with complete surveillance, surveillance failure occurred in 30 (25.2%) patients. Patients under complete surveillance were significantly more likely to be diagnosed within Milan criteria than those without surveillance (75% vs. 50%, p

This study presents a synergistic approach to the study of the aerosol optical and microphysical properties measured in La Palma, Spain, during the 2021 eruption of the Cumbre Vieja volcano (from 19 September to 13 December 2021). This study aims to characterize the different phases of the volcanic eruption using the spatio-temporal evolution of the event together with the mass concentration quantification of four different atmospheric layers. The impact of the plume’s pathway that reached the South of France is analyzed. Here, passive and active remote sensors were used, namely CL51 and CL61 ceilometers and AERONET sunphotometers. The attenuated backscattering ranged from 0.8 to 9.1 × 10−6 (msr)−1 and the volume depolarization ratio measured nearby the volcano was up to 0.3. The ash plume remained within the first 4 km agl, with intense episodes that reached mean aerosol optical depth values of up to 0.4. Thirteen study cases were selected where coarse mode was dominant over fine mode. For the data selection, the fine and coarse lidar ratios found were 3.9 ± 0.8 and 21.0 ± 3.8 sr in the north and 6.9 ± 1.8 and 30.1 ± 10.3 sr in the south. The ash mass concentration reached moderate levels with maximum values of up to 313.7 μgm−3.

Bias-flow liners (BFL) are used as part of the cooling mechanism in airplane turbines and they also enable the reduction of noise emission. The attenuating principle is based on the interaction between sound waves and air flow. This turbulent aeroacoustic interaction occurs on a microscopic level and under harsh conditions. Therefore, in order to investigate local aeroacoustic phenomena, the distribution of the local sound field impedance, defined as sound pressure over acoustic particle velocity, is measured non-invasively. This work focuses on the non-invasive measurement of the local sound pressure. A fast camera-based holographic measurement system for the two dimensional tomographic measurement of the local sound pressure with high spatial resolution is presented. It features a spatial resolution of 52 μm with a simultaneous acquisition of up to 1600 measuring points. This enables the observation of sub-mm aeroacoustic effects, which are expected in the near field over the BFL's surface, while reducing the measurement duration by three orders of magnitude compared to single point measurement systems. An experimental validation of the camera-based tomographic system is carried out by reference measurements. The system was applied at an acoustical model and an aeroacoustic model. The measured local sound pressure variations are discussed for both models. This work seeks to enable the non-invasive investigation of sound pressure, in order to further understand aeroacoustic effects, their sound attenuating properties and increase the attenuation capability of a BFL without degrading the overall performance of turbines.

Motor imagery is a complex mental task that represents muscular movement without the execution of muscular action, involving cognitive processes of motor planning and sensorimotor proprioception of the body. Since the mental task has similar behavior to that of the motor execution process, it can be used to create rehabilitation routines for patients with some motor skill impairment. However, due to the nature of this mental task, its execution is complicated. Hence, the classification of these signals in scenarios such as brain–computer interface systems tends to have a poor performance. In this work, we study in depth different forms of data representation of motor imagery EEG signals for distinct CNN-based models as well as novel EEG data representations including spectrograms and multidimensional raw data. With the aid of transfer learning, we achieve results up to 93% accuracy, exceeding the current state of the art. However, although these results are strong, they entail the use of high computational resources to generate the samples, since they are based on spectrograms. Thus, we searched further for alternative forms of EEG representations, based on 1D, 2D, and 3D variations of the raw data, leading to promising results for motor imagery classification that still exceed the state of the art. Hence, in this work, we focus on exploring alternative methods to process and improve the classification of motor imagery features with few preprocessing techniques.

Osteoporosis is defined by loss of bone mass and deteriorated bone microarchitecture. The present study compared the effects of available pharmacological and non-pharmacological agents for osteoporosis [alendronate (ALE) and concomitant supplementation of vitamin D (VD) and calcium (Ca)] with the effects of bovine colostrum (BC) supplementation in ovariectomized (OVX) and orchidectomized (ORX) rats. Seven-month-old rats were randomly allocated to: (1) placebo-control, (2) ALE group (7.5 μg/kg of body weight/day/5 times per week), (3) VD/Ca group (VD: 35 μg/kg of body weight/day/5 times per week; Ca: 13 mg/kg of body weight/day/3 times per week), and (4) BC supplementation (OVX: 1.5 g/day/5 times per week; ORX: 2 g/day/5 times per week). Following four months of supplementation, bone microarchitecture, strength and bone markers were evaluated. ALE group demonstrated significantly higher Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC and significantly lower Ct.Pr, Tb.Pr, Tb.Sp, Ct.BMD and Tb.BMD, compared to placebo (p < 0.05). BC presented significantly higher Ct.Pr, Ct.BMD, Tb.Pr, Tb.Sp, and Tb.BMD and significantly lower Ct.OV, Ct.BMC, Tb.Th, Tb.OV and Tb.BMC compared to ALE in OVX rats (p < 0.05). OVX rats receiving BC experienced a significant increase in serum ALP and OC levels post-supplementation (p < 0.05). BC supplementation may induce positive effects on bone metabolism by stimulating bone formation, but appear not to be as effective as ALE.

Efforts have been made to diagnose and predict the course of different neurodegenerative diseases through various imaging techniques. Particularly tauopathies, where the tau polypeptide is a key participant in molecular pathogenesis, have significantly increased their morbidity and mortality in the human population over the years. However, the standard approach to exploring the phenomenon of neurodegeneration in tauopathies has not been directed at understanding the molecular mechanism that causes the aberrant polymeric and fibrillar behavior of the tau protein, which forms neurofibrillary tangles that replace neuronal populations in the hippocampal and cortical regions. The main objective of this work is to implement a novel quantification protocol for different biomarkers based on pathological post-translational modifications undergone by tau in the brains of patients with tauopathies. The quantification protocol consists of an adaptation of the U-Net neural network architecture. We used the resulting segmentation masks for the quantification of combined fluorescent signals of the different molecular changes tau underwent in neurofibrillary tangles. The quantification considers the neurofibrillary tangles as an individual study structure separated from the rest of the quadrant present in the images. This allows us to detect unconventional interaction signals between the different biomarkers. Our algorithm provides information that will be fundamental to understanding the pathogenesis of dementias with another computational analysis approach in subsequent studies.

Adrenal masses are commonly found on radiographic studies performed for unrelated reasons. We report on a case of a non-functioning adrenal mass from which a needle biopsy showed a nonspecific infiltrate of polyclonal plasma cells and small lymphocytes. A definitive diagnosis of the plasma cell variant of Castleman lymphadenopathy was made only after surgical excision. While the hyaline vascular variant of Castleman lymphadenopathy has been identified in adrenal glands, this is the first report of the plasma cell variant in an adrenal mass. This case particularly underscores the importance of an excisional biopsy for proper diagnosis.

This work aims to evaluate and compare variations of a methodology for performing tensile tests on thermoplastic specimens constructed by additive manufacturing technologies (AMT) with filament deposition modeling (FDM). The testing procedures of pieces made in FDM machines do not yet have any conclusive standards because 3D printing, as a disruptive and exponentially growing technology, has not allowed enough time to reach a definitive scientific consensus. Nowadays, testing standards for injected thermoplastic parts or laminated composites are employed as substitutes with careful implementation. A comparative study was carried out on the elasticity modulus, determined within the framework of the same standard but with different measuring devices and testing machines. These machines cover a broad range from professional automated high precision machines to lab and specialized machines. Sets of 3Dprinted specimens with identical manufacturing parameters were constructed in a commercial 3D printer. An analysis of variance was performed in order to evaluate the consistency and significance of experimental data for the same polymer, considering the machine type and its corresponding setup. From the experimental data, it is concluded that, with the due care, all evaluated testing setups can reach comparable results, especially in the absence of sophisticated and expensive measuring systems.

Our program in is a 4-year combined anatomic pathology (AP) and clinical pathology (CP) program located in New Hampshire. Prior to the novel coronavirus (COVID-19) pandemic, double-headed sign-outs and multi-headed scope didactic conferences took place daily. On the autopsy service, cases were performed in-house under attending supervision, and forensic cases were performed at the off-site Office of the Medical Examiner. In CP, residents engaged in weekly didactic CP lectures and engaged in in-person resident-attending discussions, laboratory rounds, and direct patient contact on a daily basis. Institutional Universal Guidelines from the Emergency Order from New Hampshire were imposed at the beginning of the pandemic. These included exposure mitigation and employee screening strategies. Changes to resident rotations and didactic sessions, strategies to maintain resident wellness, and the program director perspectives are described. Amid the pandemic, digital pathology, teleconferencing platforms, and social media became important resources for pathology education. Digital platforms allowed groups of people to communicate and watch live presentations while social distancing. In AP, whole slide imaging allowed both attendings and residents to scan slides for personal learning, slide conferences, and didactic learning sessions. Following these measures, we supported the clinical needs of our medical center and learning needs of our residents while enacting social distancing and prevention guidelines early in the pandemic. Although the full impact of COVID-19 on pathology residency programs is still unknown, we incorporated new facets of communication technologies. These were immensely helpful in maintaining social distancing and helping to reduce the spread of disease.

We present the case of a 55-year-old woman who presented with laboratory studies concerning for acute myeloid leukemia (AML) as well as obstructive cholestasis. In similar previously reported cases, concerns of chemotherapy toxicity exacerbated by liver dysfunction or concerns of untreated, concurrent cholecystitis in a neutropenic patient often delay initiation of chemotherapy for full medical workup. At admission, our patient was started on the cytoreductive agent hydroxyurea. By day 10 of her medical workup, her liver function had improved with total bilirubin levels normalizing. At that time, full-dose 7 + 3 induction with cytarabine and daunorubicin was then initiated.

In this work, a set of novel fluorinated ionic liquids (FILs), based on different tetra-alkyl-phosphonium cations with perfluorobutanesulfonate and perfluoropentanoate anions, were synthesized and characterized in order to check their suitability to apply as engineering solvents. Thermophysical and thermal properties were both determined between 293.15 and 353.15 K, and the molecular volumes and free volumes and the coefficients of isobaric thermal expansion were determined from experimental values of refractive index and density. Lastly, the Walden plot was used to evaluate the ionicity of the novel FILs. The cytotoxicity of these compounds was also determined using the human hepatocellular carcinoma cells (HepG2) and the human colon carcinoma cells (Caco-2). Finally, the results were all discussed with the aim of understanding the behaviour of these compounds, considering the influence of the anion and the hydrogenated alkyl chain length. In summary, the new FILs synthesized in this work present adequate properties for their application in different industrial processes. Most of these compounds are liquid at room temperature with high decomposition temperatures. All phosphonium-based FILs have lower densities than conventional ionic liquids and common organic solvents, and the viscosity depends directly on the selected anion. Furthermore, the ionicity of FILs based on the sulfonate anion is higher than those based on the carboxylate anion. Finally, the phosphonium-based FILs have no significant effect on cellular viability at lower concentrations.

Category: Ankle; Trauma Introduction/Purpose: Fixation strategies for distal tibiofibular syndesmotic injuries are associated with risk of malreduction. We describe a new method of reduction and fixation of the syndesmosis with two suture buttons placed through a single sagittal tunnel through the fibula and across the tibia at the attachment sites of the anterior and posterior-inferior tibiofibular ligaments. Methods: Eighteen frozen cadaveric lower leg specimens were divided in two groups of nine and subjected to syndesmotic injury followed by reduction and fixation. Nine were repaired with the new method and 9 with the conventional method. Post-reduction CT images were obtained and compared to pre-injury CT images to assess quality of reduction. Specimens were then tested on an MTS machine and loaded between +\-5Nm at 0.5Hz of internal and external rotation for 500 cycles. Cyclic loading was paused at 0, 100, and 500 cycles to assess torsional resistance, fibular rotation, and fibular translation with the foot first internally rotated 10 degrees and then externally rotated 15 degrees. Peak torque and translation of the fibula was measured. Results: A statistically significant difference was detected between groups, with the new method of fixation showing less lateral translation of the fibula. Data that did not reach statistical significance showed a trend towards decreased post reduction translation in the sagittal plane and improved rotational alignment with the new method. Decreased fibular rotation that reached statistical significance was noted in the new technique with internal rotation at 0, 100 and 500 cycles and during external rotation at 100 and 500 cycles. No differences were noted for torsional resistance or fibular translation between groups. Conclusion: The new method of syndesmotic fixation facilitated reduction of the syndesmosis that resulted in improved alignment, and better rotational stability compared with the conventional technique. This may be a reliable alternative to current methods of syndesmosis reduction and fixation.

Near the electrostatic plasma frequency, plasma exhibits a relative permittivity near zero, and this property has been used to make transient plasma waveguides at microwave and optical wavelengths by ionizing gases with pulsed electromagnetic fields and laser radiation. However, to our knowledge, no one has constructed a steady-state RF-excited plasma waveguide for the purpose of studying its microwave attenuation and dispersion characteristics. We report here the results of investigations at 2.8–3.7 GHz of a variable-length plasma waveguide up to 30 cm long in which the plasma’s relative permittivity was as low as 0.2. De-embedded S-parameter power loss is as low as 4.6 dB and the dispersion is largely consistent with theory, although further work remains to be done.

Sign language recognition is a highly-complex problem due to the amount of static and dynamic gestures needed to represent such language, especially when it changes from country to country. This article focuses on static recognition of vowels in Colombian Sign Language. A total of 151 images were acquired for each class, and an additional non-vowel class with different scenes was also considered. The object of interest was cut out of the rest of the scene in the captured image by using color information. Subsequently, features were extracted to describe the gesture that corresponds to a vowel or to the class that does not match any vowel. Next, four sets of features were selected. The first one contained all of them; from it, three new sets were generated. The second one was extracted from a subset of features given by the Principal Component Analysis (PCA) algorithm. The third set was obtained by Sequential Feature Selection (SFS) with the FISHER measure. The last set was completed with SFS based on the performance of the K-Nearest Neighbor (KNN) algorithm. Finally, multiple classifiers were tested on each set by cross-validation. Most of the classifiers achieved a performance over 90%, which led to conclude that the proposed method allows an appropriate class distinction.

Bi2AE2Co2Ox (AE = Ca, Sr, and Ba) thermoelectric compounds were grown from the melt by the laser floating zone technique. Microstructural analysis of as-grown samples has shown the formation of well-aligned thermoelectric grains together with a relative high amount of secondary phases. On the other hand, a short (24 h) thermal treatment (810 °C for Sr, 800 °C for Ca, and 750 °C for Ba) under air, raises of thermoelectric phase content through the recombination of the secondary ones. These microstructural modifications led to a large decrease of electrical resistivity, improving the power factor. These results have been compared with samples prepared by the conventional solid state method and with the best values reported in the literature. From these data, it is possible to deduce that the high thermoelectric characteristics obtained in these samples make them very attractive for practical applications.

Glucocorticoid-induced osteoporosis (GIO) is one of the most common secondary forms of osteoporosis. GIO is partially due to the apoptosis of osteoblasts and osteocytes. In addition, high doses of dexamethasone (DEX), a synthetic glucocorticoid receptor agonist, induces neurodegeneration by initiating inflammatory processes leading to neural apoptosis. Here, a neuroprotective bovine colostrum against glucocorticoid-induced neuronal damage was investigated for its anti-apoptotic activity in glucocorticoid-treated MC3T3-E1 osteoblastic cells. A model of apoptotic osteoblastic cells was developed by exposing MC3T3-E1 cells to DEX (0–700 μM). Colostrum co-treated with DEX was executed at 0.1–5.0 mg/mL. Cell viability was measured for all treatment schedules. Caspase-3 activation was assessed to determine both osteoblast apoptosis under DEX exposure and its potential prevention by colostrum co-treatment. Glutathione reduced (GSH) was measured to determine whether DEX-mediated oxidative stress-driven apoptosis is alleviated by colostrum co-treatment. Western blot was performed to determine the levels of p-ERK1/2, Bcl-XL, Bax, and Hsp70 proteins upon DEX or DEX plus colostrum exposure. Colostrum prevented the decrease in cell viability and the increase in caspase-3 activation and oxidative stress caused by DEX exposure. Cells, upon colostrum co-treated with DEX, exhibited higher levels of p-ERK1/2 and lower levels of Bcl-XL, Bax, and Hsp70. Our data support the notion that colostrum may be able to reduce DEX-induced apoptosis possibly via the activation of the ERK pathway and modulation of the Hsp70 system. We provided preliminary evidence on how bovine colostrum, as a complex and multi-component dairy product, in addition to its neuroprotective action, may affect osteoblastic cell survival undergoing apoptosis.

Osteoporosis is characterized by bone loss. The present study aims to investigate the effects of bovine colostrum (BC) on bone metabolism using ovariectomized (OVX) and orchidectomized (ORX) rat models. Twenty-seven-week-old Wistar Han rats were randomly assigned as: (1) placebo control, (2) BC supplementation dose 1 (BC1: 0.5 g/day/OVX, 1 g/day/ORX), (3) BC supplementation dose 2 (BC2: 1 g/day/OVX, 1.5 g/day/ORX) and (4) BC supplementation dose 3 (BC3: 1.5 g/day/OVX, 2 g/day/ORX). Bone microarchitecture, strength, gene expression of VEGFA, FGF2, RANKL, RANK and OPG, and bone resorption/formation markers were assessed after four months of BC supplementation. Compared to the placebo, OVX rats in the BC1 group exhibited significantly higher cortical bone mineral content and trabecular bone mineral content (p < 0.01), while OVX rats in the BC3 group showed significantly higher trabecular bone mineral content (p < 0.05). ORX rats receiving BC dose 2 demonstrated significantly higher levels of trabecular bone mineral content (p < 0.05). Serum osteocalcin in the ORX was pointedly higher in all BC supplementation groups than the placebo (BC1: p < 0.05; BC2, BC3: p < 0.001). Higher doses of BC induced significantly higher relative mRNA expression of OPG, VEGFA, FGF2 and RANKL (p < 0.05). BC supplementation improves bone metabolism of OVX and ORX rats, which might be associated with the activation of the VEGFA, FGF2 and RANKL/RANK/OPG pathways.