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Background: Breast cancer is the most common cancer in women, and breast reconstruction improves the patient's quality of life. Autologous breast reconstruction provides benefits of natural appearance, feel, and long-term results without implant-associated problems. However, thin patients are not always suitable for standard autologous reconstructions. In these patients, an omental flap could be a useful alternative. The aim of this review was to provide an overview of the literature regarding the clinical outcomes of omental flaps in breast reconstruction. Methods: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using the Medline and Embase databases up to November 1, 2023. Study outcomes were type of flap, tissue transfer, cosmetic outcomes, and short- and long-term complications. Results: Eleven studies covering 985 reconstructions in 969 patients were included. The omentum was mostly laparoscopically harvested (88.6%) and a pedicled reconstruction was mostly performed (91.2%). The most commonly reported short-term complications were wound infections at the donor site (5.8%), partial flap necrosis, and fat necrosis. In the long term, epigastric, umbilical and tunnel hernias, and epigastric bulging were observed. Satisfactory cosmetic results were reported by the patients (88.7%) and professionals (80.0%). Conclusion: Breast reconstruction using an omental flap can be performed in unilateral reconstructions with acceptable donor-site morbidity if laparoscopically harvested. In general, satisfactory cosmetic outcomes were reported and it appears to be a suitable alternative for selected patients who prefer autologous, unilateral breast reconstruction. Further research is necessary to determine the ideal candidates for this reconstruction and the long-term effects of an omentectomy in young patients.

This paper presents an efficient and secure method for updating firmware in IoT devices using LoRaWAN network resources and communication protocols. The proposed method involves dividing the firmware into fragments, storing them in the application server’s database, and transmitting them to remote IoT devices via downlink messages, without necessitating any changes to the device’s class. This approach can be replicated across any IoT LoRaWAN device, offering a robust and scalable solution for large-scale firmware updates while ensuring data security and integrity. The proposed method significantly reduces the downtime of IoT devices and enhances the energy efficiency of the update process. The method was validated by updating a block in the program memory, associated to a specific functionality of the IoT end device. The associated Intel Hex file was segmented into 17 LoRaWAN downlink frames with an average size of 46 bytes. Upon receiving the complete firmware update, the microcontroller employs self-programming techniques that restrict the update process to specific rows of the program memory, avoiding interruptions or reboots. The update process was successfully completed in 51.33 ms, resulting in a downtime of 16.88 ms. This method demonstrates improved energy efficiency compared to existing solutions while preserving the communication network’s capacity, making it an adequate solution for remote devices in LoRaWAN networks.

Alastair Thomson,1 Lucinda Gunn,1 Deborah Victor,1 Ellis Adamson,1 Kashyap Thakrar2 1Oncology Department, Sunrise Centre, Royal Cornwall Hospital, Truro, Cornwall, UK; 2Accord-UK Ltd, Barnstaple, Devon, UKCorrespondence: Alastair Thomson, Oncology department, Sunrise Centre, Royal Cornwall Hospital, Truro, Cornwall, TR1 3LJ, UK, Tel +44 (0)1872 250000, Email alastairthomson1@nhs.netBackground: In the UK, relugolix, an oral gonadotropin-releasing hormone receptor antagonist, is indicated for advanced hormone-sensitive prostate cancer, and as neo-adjuvant and adjuvant treatment in combination with radiotherapy in patients with high-risk localised or locally advanced hormone-dependent prostate cancer. Experience with the combination of oral relugolix plus oral enzalutamide is limited.Case Presentation: A white British male (66 years old) with a history of myelodysplastic syndrome, chronic neutropenia and indeterminate colitis presented with metastatic adenocarcinoma of the prostate gland. The patient started subcutaneous leuprorelin acetate and oral enzalutamide. After 8 weeks, the oral enzalutamide dose was reduced because of fatigue. Following the second leuprorelin injection, the patient developed a subcutaneous abscess that required surgical incision and drainage. The patient switched to oral relugolix and continued with oral enzalutamide. Within 3 months of commencing leuprorelin and enzalutamide the prostate specific antigen (PSA) concentration fell from a peak of 269.00 ng/mL to 2.55 ng/mL. Following the switch to oral relugolix plus enzalutamide, the PSA remained stable until the most recent assessment 11 months later. Relugolix plus enzalutamide was well tolerated.Conclusion: Relugolix plus enzalutamide produced a sustained reduction in PSA and the combination was well tolerated. Further research including real world data should assess relugolix in doublet and triplet combinations for prostate cancer.Plain Language Summary: Oral (by mouth) relugolix can treat certain men with hormone sensitive prostate cancer. Studies are underway looking at relugolix combined with other drugs, such as oral enzalutamide, and at various stages of prostate cancer. Dr Thomson et al report the case of a man with other serious diseases who took oral relugolix and oral enzalutamide after experiencing side effects with injectable drugs. His levels of prostate specific antigen (PSA), which indicates prostate cancer control (the lower the better), fell markedly after starting treatment and, after switching to relugolix, remained stable for 11 months. He tolerated relugolix plus enzalutamide well.Keywords: relugolix, enzalutamide, prostate cancer, gonadotropin-releasing hormone receptor antagonist, prostate specific antigen

Neurofibromatosis 1 (NF1) represents a cluster of clinical features based on the National Institute of Health(NIH) diagnostic criteria. It is a multi-systemic disease with progressive features characterized by variable expression. NF1 is associated with an increased risk of malignancies including breast cancer. Presented was a 56 year old woman with a painless lump in the right breast in the past 15 months. Clinical evaluation revealed features of NF1 and an advanced right breast cancer. Histologic evaluation revealed an invasive ductal carcinoma and she was offered a right modified radical mastectomy. Due to clinical presentation with discrete lesions, NF1 may be diagnosed at presentation with malignancy. Clinicians are urged to be familiar with the subtle features of NF1 for early diagnosis that is largely clinical. Institution of early breast cancer surveillance in patients with NF1 is recommended for early diagnosis and improved outcomes.

Introduction. Optical fibers are widely used for high-bandwidth transmitting communication signals over long distances. The key feature enabling this performance is signal low attenuation, that is signals experience minimal power loss propagating along the optical fiber. One of the factors influencing power loss during information transmission is the fiber bending. Bending can increase the signal transmission power loss of an optical fiber because of both macrobending and microbending. Studying the dependence of signal power losses when bending on waveguide parameters makes it possible to control the signal power losses of an optical fiber during information transmission. Aim of the Study. The study ia aimed at evaluating the effect of microbending on the field and energy of a weakly guiding optical fiber with a gradient refractive index profile in a single-mode regime. Materials and Methods. From the equations for the fields of straight and curved sections of weakly guiding fiber for an arbitrary gradient profile of the refractive index with the help of the subsequent solution of inhomogeneous Helmholtz equations by the Green’s function method, there were obtained expressions for relative energy: the ratio of the field energy of the fiber curved section to the field energy of the fiber straight section (in the first approximation for a single-mode regime). Results. The obtained expression for the relative energy depends on two parameters: the waveguide parameter and the ratio of the optical fiber radius to the radius of curvature. For the quadratic case of a power-law profile, as the closest to the actually used one, numerical calculations were used to construct the dependences of the relative energy on the parameter characterizing the bending for different values of the waveguide parameter. Discussion and Conclusion. It has been shown that in the case of microbending, the longer the wavelength or the smaller the fiber radius, the lower the losses. The results obtained can be used in calculating optical fiber profiles designed to operate in a bent state and eliminate expensive experimental modeling of light guides and in designing waveguides to solve specific applications, in particular, to increase energy efficiency, reliability and performance of the measuring instruments.

Abstract Shell ring archaeological sites are one of the most visible site types along the lower South Atlantic Coast of the United States. These cultural sites are large, circular to arcuate piles of mollusk shells with some reaching over three meters in elevation and over 100 m in diameter. They are comprised largely of mollusk shells (e.g., Eastern oyster, Crassostrea virginica), but also contain early pottery, nonhuman faunal remains, and other artifacts. Our work establishes that they represent the earliest widespread Native American villages occupied year-round in the Eastern Woodlands of North America. Significantly, our results from sea-level modelling and isotope geochemistry on mollusks establish that the inhabitants of these earliest villages (ca. 5000–3800 yrs. BP) lived within a fluctuating coastal environment, harvested certain resources year-round, and targeted diverse habitats across the estuaries. Both the growth and decline of these earliest villages are associated with a concomitant rise and lowering of sea level that impacted the productivity of the oyster reef fishery along the South Atlantic Coast. Despite these large-scale environmental changes, this research indicates that Native American fishing villages persisted along the coast for over 1000 years.

Hydroxyapatite (HAp) is a popular ceramic biomaterial, which has extensively been employed in numerous biomedical applications. It has drawn the attention of scientists primarily owing to its properties similar to the bones and teeth of human beings. Due to its organic similarity, HAp has exceptional biocompatibility and can activate osteoconduction and osteoinduction occurrence. Hence, HAp has been used in a broad collection of healing applications extending from common dental implant, and bioactive coatings on grafts to purposefully premeditated drug delivery methods, and even for tissue engineering (TE) applications. The production method is essential in controlling the physicochemical properties of HAp, which in turn affects its mechanical and biological properties. The anticipated physiognomies of HAp can be accomplished using a suitable technique of production and sources. This in-depth review discussed the various natural sources of HAp, and synthesis techniques for producing HAp, alongside their advantages and disadvantages, applications, and essentials of HAp for therapeutic applications. From the review, it was found that the sol–gel route is preferred over other routes because of its even molecular mixing, high purity of products, low production temperature, and ability to synthesize nanosized particles of HAp. As a result, it is provisional that upon the cautious blend of key considerations such as sources, synthesis technique, and production parameters for the manufacture of natural HAp (NHAp), mechanical properties can be improved and the product can be employed as a drug delivery system. These are important extents for the prospect of the research.

IntroductionElasmobranchs, such as sharks and rays, are among the world’s most endangered vertebrates, with over 70% loss in abundance over the past 50 years due to human impacts. Zooarchaeological baselines of elasmobranch diversity, distribution, and exploitation hold great promise for contributing essential historical contexts in the assessment of contemporary patterns in their taxonomic diversity and vulnerability to human-caused extinction. Yet, the historical ecology of elasmobranchs receives relatively less archaeological attention compared to that of ray-finned fishes or marine mammals, largely due to issues of taxonomic resolution across zooarchaeological identifications.MethodsWe explore the use of Zooarchaeology by Mass Spectrometry (ZooMS) for species identification in this unstudied group, using an archaeological case study from the marine environments of the Florida Keys, a marine biodiversity hotspot that is home to an array of elasmobranch species and conservation efforts. By comparison with 39 modern reference species, we could distinguish 12 taxa within the zooarchaeological assemblage from the Clupper archaeological site (Upper Matecumbe Key) that included nine sharks, two rays and a sawfish.Results and discussionThe results indicate that, through additional complexity of the collagen peptide mass fingerprint, obtained due to the presence of the cartilaginous type II collagen, ZooMS collagen peptide mass fingerprinting provides exceptionally high taxonomic resolution in this group, yielding species-level identifications in all cases where sufficient reference material was used. This case study also highlights the added value of ZooMS for taxa that are more difficult to distinguish in zooarchaeological analyses, such as vertebrae of the Atlantic sharpnose shark (Rhizoprionodon terraenovae) and the hammerhead sharks (Sphyrna spp.) in the Florida Keys. Therefore, the application of collagen peptide mass fingerprinting to elasmobranchs offers great potential to improve our understanding of their archaeological past and historical ecology.

Author’s innovative technical solutions for modernizing existing burner devices of the GP type with low emissions of toxic nitrogen oxides, protected by patents for utility models, were analyzed and recommended for implementation in the oil and gas industry. New designs of GP burners with the placement of an oil nozzle in the embrasure, with additional equipment with a special pipe with a steam sprayer into the firebox, as well as with an additional arrangement of an air flow separator installed in the mixing chamber and equipped with nozzles for supplying compressed air, which increases the environmental friendliness of their operation by reducing emissions of nitrogen oxides from incomplete combustion products.

The reaction of ZrCl4 or HfCl4 with excess 2-methylpropanoic acid when boiling under reflux has been studied. The formation of polynuclear Zr and Hf complexes of the composition M2O(i-C3H7CO2)6 during prolonged reflux of the reaction mixtures was found. The complexes are very sensitive to hydrolysis, forming hexanuclear [M6(O)4(OH)4(i-C3H7CO2)12]. The reactions have a general character for aliphatic acids and can be used as an alternative to the known methods for the synthesis of polynuclear carboxylate clusters of Group 4 metals. The crystal and molecular structures of previously undescribed {[Hf6(μ3-O)4(μ3-OH)4(i-C3H7CO2)12(H2O)]·3i-C3H7COOH} have been determined. The molecular structure is a completely asymmetric hexanuclear cluster containing six Hf(IV) atoms united by a 4:4 μ3-O/OH system of bridges, and stabilized by twelve 2-methylpropanoate ligands, eight of which are bidentate bridging, three are chelating, and one is monodentate. The crystal structure of the complex includes three independent solvating 2-methylpropanoic acid molecules. The obtained IR spectroscopy data make it possible to determine the type of complexes in the reaction mixture. The results of the study may be useful for improving the catalytic systems for ethylene oligomerization.

Рost-COVID-19 syndrome (PS) is one of the medical and social problem. According to WHO, 10–20% of COVID-19 patients suffer from PS. The use of medical gases – inhaled nitric oxide (iNO) and molecular hydrogen (iH2) – may influence on the mechanisms of development PC. Aim. To evaluate the safety and efficacy of the combined inhalation of NO and H2 (iNO/iH2) in patients with respiratory manifestations of PS. Materials and methods. 34 patients with PS (11 men/23 women, 60.0±11.7 years) were included in the prospective open-label controlled study in parallel groups: the main group (n=17) received iNO/iH2 for 90 minutes once a day for 10 days (concentration of NO 60 ppm, H24% in the gas mixture), the control group (n=17) didn’t receive inhalations. The period from the confirmation of COVID-19 to the start of the study was 641.8±230.5 days. The groups did not differ in the baseline parameters. The clinical symptoms (from the self-observation diary and mMRC questionnaires, "dyspnea language"), FAS, HADS, SF-36 scores, 6-minute walk test, the blood serum parameters of oxidative stress, the dynamics of the microcirculation in the eye bulbar conjunctiva were evaluated. The individual dose of iNO has chosen during a 15-minute test (the positive dynamics of the microcirculation have indicated that the dose was selected correctly). Results. The decrease the symptoms severity, such as dyspnea, cough, fatigue and palpitations (p0.005), the increase in SF-36 questionnaire scores (p=0.006) and a reducing of FAS score (p=0.001), as well as the anxiety component of HADS (p=0.02) were revealed at the end of treatment in the main group compared to the control group. We observed an improvement in distance walked (p=0.01) and the values SpO2 (p=0.04) in 6-minute walk test, the increase in the volumetric blood flow velocity in venules (p0.001), and the date in oxidative damage (p0.001) and antioxidant activity (p=0.03) parameters in the blood serum. Conclusion. The results of the study demonstrate clinical efficacy iNO/iH2 on clinical indicators, parameters of oxidative stress and microcirculation in patients with PS.

Shocked POstarburst Galaxies (SPOGs) exhibit both emission lines suggestive of shock-heated gas and poststarburst-like stellar absorption, resulting in a unique subset for galaxy evolution studies. We have observed 77 galaxies that fulfilled the SPOG criteria selection using the DeVeny Spectrograph on the Lowell Discovery Telescope. Our long-slit minor axis spectra detect H α and [O III ] in some SPOGs out to 6 kpc above the galactic plane. We find extraplanar ionized gas in 31 targets of our sample overall. Using their internal and external kinematics, we argue that 22 galaxies host outflows with ionized gas masses ranging from 10 ^2 M _⊙ to 10 ^5 M _⊙ . The rest are likely extended diffuse ionized gas. A positive correlation exists between active galactic nuclei (AGN) luminosity and the extraplanar gas extent, velocity dispersion, and mass—suggesting that the AGN may indeed drive the outflows detected in AGN hosts. The low masses of the extraplanar gas suggest that these outflows are not depleting each galaxy’s gas reserves. The outflows, therefore, are not likely a significant quenching mechanism in these SPOGs.

Background. The purpose of the work is the numerical modeling of unsteady convective heat exchange of an electrically conductive fluid between two concentric spheres, taking into account the dissipation of Joule heat, viscous, inertial, lifting and magnetic forces at low values of the magnetic Reynolds number. Materials and methods. Foe solving the problem, the finite element method is used. In a dimensionless form, the problem in the variables vortex, stream function, temperature and magnetic induction is solved in a spherical coordinate system, taking into account symmetry in longitude. Results. Nonstationary temperature fields, a stream function field, a vortex field, fields of the radial and azimuthal components of magnetic induction and the distribution of local Nusselt numbers in a spherical layer of an electrically conductive liquid for small values of the magnetic Reynolds number were obtained. Conclusions. The results obtained in the work can be applied in the study of magnetohydrodynamic and thermal processes and their application for the development of new installations and instruments, the creation of new methods and models, and expanding the understanding of the nature of the occurrence of magnetohydrodynamic phenomena taking into account heat and mass transfer processes.

Abstract We present new chronologies that inform the timing and tempo of shell ring and shell mound construction on the South Atlantic Bight. Our project combines recently acquired dates with legacy radiocarbon dates from over 25 rings and mounds to provide a higher-resolution chronology regarding the occupation and formation of this larger landscape of the earliest fishing villages along the East Coast of the United States. We resolve the ordering and timing of occupation of these rings and mounds through Bayesian statistical modeling. These new models historicize and contextualize these shell rings in ways previously impossible. Specifically, our new chronologies of these villages indicate that the earliest villages were established prior to the invention of pottery. The early period of village establishment evidences isolated village rings, whereas later periods seem to have more villages, but these appear to have been relocated to other areas and/or islands over time. Shell mounds are fewer in number, are spread throughout the time period, and may represent special purpose sites compared to shell-rings. Once villages spread, they quickly adopted new technologies (i.e., pottery) and created new institutions and practiced village relocation, which allowed this way of life to persist for more than a thousand years.

Abstract Background The growth of urban dwelling populations globally has led to rapid increases of research and policy initiatives addressing associations between the built environment and physical activity (PA). Given this rapid proliferation, it is important to identify priority areas and research questions for moving the field forward. The objective of this study was to identify and compare research priorities on the built environment and PA among researchers and knowledge users (e.g., policy makers, practitioners). Methods Between September 2022 and April 2023, a three-round, modified Delphi survey was conducted among two independent panels of international researchers (n = 38) and knowledge users (n = 23) to identify similarities and differences in perceived research priorities on the built environment and PA and generate twin ‘top 10’ lists of the most important research needs. Results From a broad range of self-identified issues, both panels ranked in common the most pressing research priorities including stronger study designs such as natural experiments, research that examines inequalities and inequities, establishing the cost effectiveness of interventions, safety and injuries related to engagement in active transportation (AT), and considerations for climate change and climate adaptation. Additional priorities identified by researchers included: implementation science, research that incorporates Indigenous perspectives, land-use policies, built environments that support active aging, and participatory research. Additional priorities identified by knowledge users included: built environments and PA among people living with disabilities and a need for national data on trip chaining, multi-modal travel, and non-work or school-related AT. Conclusions Five common research priorities between the two groups emerged, including (1) to better understand causality, (2) interactions with the natural environment, (3) economic evaluations, (4) social disparities, and (5) preventable AT-related injuries. The findings may help set directions for future research, interdisciplinary and intersectoral collaborations, and funding opportunities.

The study reviews and recommends fundamentally new technical solutions in the field of ecology and safety in the technosphere, confirmed by patents for inventions and utility models developed by scientists and graduate students of the Department of Technosphere Safety of the Far Eastern State Transport University. Innovative developments that are of practical interest and deserve attention include installations for preparing water-oil emulsions for combustion, energy-saving devices for environmentally friendly combustion of liquid fuels, rational designs of low-toxic gas and oil burners, as well as effective filter-cyclone and group cyclone devices for purification of flue gases from coal and fuel oil boiler and furnace units.

The adoption of more sedentary residential practices is a long process in which groups shift in size, permanence, makeup, and even location in response to the social, demographic, ecological, and subsistence pressures associated with settling down. Coastal peoples living in the Southeast U.S. are among the first to adopt more sedentary lifeways in North America as evidenced by their creation of dozens of large circular or arcing shell middens during the end of the Middle Holocene and start of the Late Holocene. Relying on material culture studies and AMS radiocarbon data refined using Bayesian statistical modeling, we investigate the sequential establishment and abandonment of three village sites built over more than 300 years and located only a few kilometers apart. These studies reveal important insights into the process of adopting more sedentary practices in the region and how local communities adapted to associated pressures.

[This corrects the article DOI: 10.1371/journal.pone.0258979.].

Abstract Background Over 50% of all critically ill children develop preventable intensive care unit-acquired morbidity. Early and progressive mobility is associated with improved outcomes in critically ill adults including shortened duration of mechanical ventilation and improved muscle strength. However, the clinical effectiveness of early and progressive mobility in the pediatric intensive care unit has never been rigorously studied. The objective of the study is to evaluate if the PICU Up! intervention, delivered in real-world conditions, decreases mechanical ventilation duration (primary outcome) and improves delirium and functional status compared to usual care in critically ill children. Additionally, the study aims to identify factors associated with reliable PICU Up! delivery. Methods The PICU Up! trial is a stepped-wedge, cluster-randomized trial of a pragmatic, interprofessional, and multifaceted early mobility intervention (PICU Up!) conducted in 10 pediatric intensive care units (PICUs). The trial’s primary outcome is days alive free of mechanical ventilation (through day 21). Secondary outcomes include days alive and delirium- and coma-free (ADCF), days alive and coma-free (ACF), days alive, as well as functional status at the earlier of PICU discharge or day 21. Over a 2-year period, data will be collected on 1,440 PICU patients. The study includes an embedded process evaluation to identify factors associated with reliable PICU Up! delivery. Discussion This study will examine whether a multifaceted strategy to optimize early mobility affects the duration of mechanical ventilation, delirium incidence, and functional outcomes in critically ill children. This study will provide new and important evidence on ways to optimize short and long-term outcomes for pediatric patients. Trial registration ClinicalTrials.gov NCT04989790. Registered on August 4, 2021.

This study presents an early-stage design exploration of NRG-Foam, an innovative insulation material composed of cementitious foam doped with microencapsulated phase change materials (MPCMs). The study comprises the static part that utilizes life cycle assessment and life cycle costing assessment for getting insight into the impacts of the NRG-Foam production process and the dynamic part that identifies the trade-offs between performance characteristics of NRG-Foam using multi-objective optimization. The production of MPCMs was found to be a major contributor to environmental impacts while the addition of small amounts of reduced graphene oxide amplifies the impacts even further. The hot spot analysis pinpointed high electricity consumption as the main driver of environmental impacts. A multi-objective optimization analysis revealed trade-offs between performance characteristics, emphasizing the necessity of compromises during material development. The selection of the MPCM type was shown to be determinative of the final properties of NRG-Foam.

En México Neogale frenata se distribuye en casi todo el pais, sin embargo, la especie ha sido poco estudiada y la información sobre su historia natural es relativamente escasa. Reportamos cuatro nuevos registros de N. frenata obtenidos mediante fototrampeo en la región de Calakmul. En esta nota se reporta el segundo registro formal de este mamífero para el estado de Campeche y el primero para la región, lo que eleva el total de registros para esta especie a 7 en el estado.

This study aims to determine the effectiveness of administering 80 ppm nitric oxide in reducing kidney injury, mitochondrial dysfunction and regulated cell death in kidneys during experimental perfusion. Twenty-four sheep were randomized into four groups: two groups received 80 ppm NO conditioning with 90 min of cardiopulmonary bypass (CPB + NO) or 90 min of CPB and hypothermic circulatory arrest (CPB + CA + NO), while two groups received sham protocols (CPB and CPB + CA). Kidney injury was assessed using laboratory (neutrophil gelatinase-associated lipocalin, an acute kidney injury biomarker) and morphological methods (morphometric histological changes in kidney biopsy specimens). A kidney biopsy was performed 60 min after weaning from mechanical perfusion. NO did not increase the concentrations of inhaled NO2 and methemoglobin significantly. The NO-conditioning groups showed less severe kidney injury and mitochondrial dysfunction, with statistical significance in the CPB + NO group and reduced tumor necrosis factor-α expression as a trigger of apoptosis and necroptosis in renal tissue in the CPB + CA + NO group compared to the CPB + CA group. The severity of mitochondrial dysfunction in renal tissue was insignificantly lower in the NO-conditioning groups. We conclude that NO administration is safe and effective at reducing kidney injury, mitochondrial dysfunction and regulated cell death in kidneys during experimental CPB.

Introduction. We consider a weakly conductive gradient fiber in the single-mode regime and solve the equation for the electric field in the core of this fiber in a general form in the first approximation. The aim of this study is to study the field and energy in the core of a weakly conductive gradient fiber without taking into account the polarization in the single-mode regime in the case of a power-law (generally) refractive index profile. Materials and Methods. From Maxwell’s equations for dielectric media, there was derived an equation for the field in a fiber with gradient refractive index profile. Making the appropriate substitutions, replacing the zero-order Bessel function with a Gaussian function, and making the necessary approximation of the resulting equation, we arrive at an equation that we solve by the Wentzel – Kramers – Brillouin method and obtain analytical expressions for the field and energy inside waveguide for an arbitrary degree of the refractive index. Results. There was obtained a solution of the equation for the field in fiber with a powerlaw refractive index profile. Numerical calculations were carried out. A graph of the dependence of a dimensionless quantity – “normalized” energy – on the waveguide parameter for the first five powers of the profile (n = 1, 2, 3, 4, 5) was plotted. Discussion and Conclusion. It is shown that the energy increases faster for the profile with n = 1, and after this value, the energy for the profile with n = 1 increases sharply, and for n > 1, the energy growth decreases with increasing n. The results obtained in this work can be used for creating an energy-efficient core, for carrying out a possible analysis of information transmission, and for designing waveguides taking into account specific applications.

Este es un estudio de caso sobre un litigio que ha sacudido a Ecuador por más de tres décadas. Este caso es un laboratorio vivo para estudiar cómo las estrategias de litigio transnacional se ven influenciadas y nutridas por las relaciones internacionales, el derecho internacional público, la política y el derecho comparado. A finales de la década de 1990, los hermanos Isaías pasaron de ser los hombres más ricos y poderosos de Ecuador, a ser acusados como los culpables del mayor desfalco financiero en la historia. El Estado incautó miles de millones de dólares en bienes de los Isaías y comenzó una batalla legal transnacional de veinte años. Este trabajo tiene tres objetivos. Primero, hacer un relato riguroso de la historia procesal de uno de los juicios más complejos y controversiales de la historia de Ecuador con posibles efectos en América Latina. Luego, estudiar su impacto en la Doctrina de Acto e Estado. Finalmente, estudiar cómo el litigio transnacional en el ámbito de los derechos humanos ante el Sistema Universal puede convertirse en un camino altamente efectivo para la protección de los intereses patrimoniales. Este ensayo relata uno de los casos de litigio transnacional más intensos e interesantes de América Latina y sistematiza sus lecciones.

The results of direct thrust measurements of the thruster with multiple thrust vectoring capability utilizing Kr are presented. The thruster is a 2U size system. The tested bi-directional plasma thruster consists of the thruster head, inbuilt rf generator creating 9 MHz current applied to the antenna, inbuilt power supply for the set of electromagnets, and thruster control system. The thruster head consists of the set of electromagnets, open-ended gas discharge chamber, and antenna. During thrust measurements, the magnitude and configuration of the external static magnetic field, the propellant flow rate, and the power modes of the rf generator are changed. The magnitude of the magnetic field in current units is adjusted in the range of 3…5 A. The propellant flow rate is adjusted in the range of 2…100 sccm. The power modes of the rf generator are adjusted in the range of 50…250 where the value 250 corresponds to a power of 100 W. The dynamic background pressure in the vacuum chamber is 0.1 Pa at 100 sccm. Two specific thrust modes are defined: the high thrust mode (∼7 mN) and the high specific impulse mode (∼900 s).

Meaningful collaborations between archaeologists and descendant communities and nations is a necessary component of archaeological practice in the 2020s and beyond. While calls for decolonising the social sciences and humanities have become a common refrain, practical methodologies for supplanting settler-colonial research practice have been less apparent. We detail how the development of independent radiocarbon-based chronologies in archaeology is one such substantive path forward. As a joint group of Indigenous and Euro-American and Euro-Canadian researchers, we outline how collaborative research agendas that privilege the knowledge and interests of descendant communities and include independent chronology building can be developed and achieved, securing mutual benefit and distributing authority in the construction of archaeologically derived Indigenous histories.

In the above paper [1], the following corrections are necessary.

Muhammad Imran Ahmad,1 Muhammad Umair Khan,2,3 Sudha Kodali,1,4 Akshay Shetty,1,4 S Michelle Bell,4 David Victor1,4 1Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital Houston, Houston, TX, USA; 2Department of Gastroenterology and Hepatology, Hamad Medical Corporation, Doha, Qatar; 3ECPE- Executive and Continuing Professional Education, Harvard T.H Chan School of Public Health, Boston, MA, 02115-5810, USA; 4Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX, USACorrespondence: David Victor, Associate Professor of Clinical Medicine, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX, USA, Email Dwvictor@houstonmethodist.orgAbstract: Obesity has been labeled as the global pandemic of the 21st century, resulting from a sedentary lifestyle and caloric excess. Nonalcoholic fatty liver disease (NAFLD), characterized by excessive hepatic steatosis, is strongly associated with obesity and metabolic syndrome and is estimated to be present in one-quarter of the world population, making it the most common cause of the chronic liver disease (CLD). NAFLD spectrum varies from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. The burden of NAFLD has been predicted to increase in the coming decades resulting in increased rates of decompensated cirrhosis, hepatocellular carcinoma (HCC), and liver-related deaths. In the current review, we describe the pathophysiology of NAFLD and NASH, risk factors associated with disease progression, related complications, and mortality. Later, we have discussed the changing epidemiology of HCC, with NAFLD emerging as the most common cause of CLD and HCC. We have also addressed the risk factors of HCC development in the NAFLD population (including demographic, metabolic, genetic, dietary, and lifestyle factors), presentation of NAFLD-associated HCC, its prognosis, and the issue of HCC development in non-cirrhotic NAFLD. Lastly, the problems related to HCC screening in the NAFLD population, the remaining challenges, and future directions, especially the need to identify the high-risk individuals, will be discussed. We will conclude the review by summarizing the clinical evidence for treating fibrosis and preventing HCC in those at risk with NAFLD-associated HCC.Keywords: nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, hepatocellular carcinoma, metabolic syndrome, HCC screening

ABSTRACT: Background: This study examines the impact of the COVID-19 pandemic on health care–associated infection (HAI) incidence in low- and middle-income countries (LMICs). Methods: Patients from 7 LMICs were followed up during hospital intensive care unit (ICU) stays from January 2019 to May 2020. HAI rates were calculated using the International Nosocomial Infection Control Consortium (INICC) Surveillance Online System applying the Centers for Disease Control and Prevention's National Healthcare Safety Network (CDC-NHSN) criteria. Pre–COVID-19 rates for 2019 were compared with COVID-19 era rates for 2020 for central line–associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated events (VAEs), mortality, and length of stay (LOS). Results: A total of 7,775 patients were followed up for 49,506 bed days. The 2019 to 2020 rate comparisons were 2.54 and 4.73 CLABSIs per 1,000 central line days (risk ratio [RR] = 1.85, p = .0006), 9.71 and 12.58 VAEs per 1,000 mechanical ventilator days (RR = 1.29, p = .10), and 1.64 and 1.43 CAUTIs per 1,000 urinary catheter days (RR = 1.14; p = .69). Mortality rates were 15.2% and 23.2% for 2019 and 2020 (RR = 1.42; p < .0001), respectively. Mean LOS for 2019 and 2020 were 6.02 and 7.54 days (RR = 1.21, p < .0001), respectively. Discussion: This study documents an increase in HAI rates in 7 LMICs during the first 5 months of the COVID-19 pandemic and highlights the need to reprioritize and return to conventional infection prevention practices.

‘Commercial fisheries have decimated keystone species, including oysters in the past 200 years. Here, the authors examine how Indigenous oyster harvest in North America and Australia was managed across 10,000 years, advocating for effective future stewardship of oyster reefs by centering Indigenous peoples.’

Abstract Introduction Survivors of acute respiratory failure (ARF) commonly experience long-lasting physical, cognitive, and/or mental health impairments. Unmet medication needs occurring immediately after hospital discharge may have an important effect on subsequent recovery. Methods and analysis In this multicenter prospective cohort study, we enrolled ARF survivors who were discharged directly home from their acute care hospitalization. The primary exposure was unmet medication needs. The primary outcome was hospital readmission or death within 3 months after discharge. We performed a propensity score analysis, using inverse probability weighting for the primary exposure, to evaluate the exposure–outcome association, with an a priori sample size of 200 ARF survivors. Results We enrolled 200 ARF survivors, of whom 107 (53%) were female and 77 (39%) were people of color. Median (IQR) age was 55 (43–66) years, APACHE II score 20 (15–26) points, and hospital length of stay 14 (9–21) days. Of the 200 participants, 195 (98%) were in the analytic cohort. One hundred fourteen (57%) patients had at least one unmet medication need; the proportion of medication needs that were unmet was 6% (0–15%). Fifty-six (29%) patients were readmitted or died by 3 months; 10 (5%) died within 3 months. Unmet needs were not associated (risk ratio 1.25; 95% CI 0.75–2.1) with hospital readmission or death, although a higher proportion of unmet needs may have been associated with increased hospital readmission (risk ratio 1.7; 95% CI 0.96–3.1) and decreased mortality (risk ratio 0.13; 95% CI 0.02–0.99). Discussion Unmet medication needs are common among survivors of acute respiratory failure shortly after discharge home. The association of unmet medication needs with 3-month readmission and mortality is complex and requires additional investigation to inform clinical trials of interventions to reduce unmet medication needs. Study registration number: NCT03738774 . The study was prospectively registered before enrollment of the first patient.

Mid-frequency instability (MFI) generally limits the application of step motors with constant-voltage drive to a speed range well below the theoretical limit imposed by inductance, back EMF, and friction torque. Analytical studies of MFI in specific step motor types and configurations have been reported in the literature, each focused on a particular method of analysis. The goal of this paper is to develop a single model structure and method of dynamic stability analysis, applicable to all step motors. To this end, a generalized $n$ -phase step motor dynamical system model applicable to a broad range of permanent-magnet hybrid (PMH) and variable-reluctance (VR) step motors is developed. Beginning with a physical model and working from first principles, the ( $n+2$ )th-order nonlinear time-varying (NLTV) state equation is developed. Next, a Park transform for the generalized $n$ -phase step motor is applied, resulting in a fourth-order NLTV state equation and a set of $n$ -2 first-order LTI state equations. The fourth-order NLTV system is then solved at constant speed and linearized about the solution, resulting in a fourth-order linear time-invariant (LTI) state equation. Finally, the dynamic performance and stability are determined by examining the eigenvalues of the LTI system. The scope of parameterization includes: motor type (PMH or VR); number and arrangement of poles, stator teeth, and rotor teeth; number of electrical phases ( $n =2$ or odd); magnetic circuit type (uni-phase or multi-phase); winding configuration; and electrical state variable (current or flux linkage). Examples are given to illustrate the method and computer simulations are used to verify the results.

This work proposes a methodology based on multicriteria decision aid (MCDA) and a cluster analysis to identify ideal locations for the installation of police facilities or vehicle parking and policing around stadiums in Recife, Brazil, during potential violent sports events (criminal occurrences from football supporters or fanbases). A K-means unsupervised clustering algorithm is used to group criminal data into homogeneous clusters based on their characteristics. Each type of criminal occurrence is linked to a single cluster. The optimal location is addressed based on the PROMETHEE method (Preference Ranking Organization Method for Enrichment Evaluation), allowing clusters to be organized into a hierarchy based on the number of facilities (N), the average distance (D) from the criminal occurrence to the associated cluster, and the coverage level (C), which is the proportion of crime occurring in a location less than 500 m from the associated cluster. Through a data analysis of crimes and violence in the region, this study seeks to identify patterns of criminal behaviour and high-risk areas to determine the most strategic locations for police units and enhance the public security decision-making process. The choice for the k parameters ranged from 1 to 30, incorporating all regions of the analysis, with a computational cost of 43 min of running time using an Intel Core i3-3217U (1800 GHz and 10 GB of RAM). This approach and methodology can be useful for supporting public security policies in the region and can contribute to reducing violence around stadiums. The empirical application can help guide public managers’ decisions regarding resource allocation and the implementation of more effective security policies, with the aim of ensuring a safer environment for fans and residents in the areas near stadiums.

Background: One of the major challenges that has driven the spread of Coronavirus Disease 2019 (COVID-19) worldwide is the burden of enforcing the preventive measures required to contain the pandemic. Enforcement of COVID-19 precautionary behaviour should not be homogenous; every country needs to be creative to ensure that humane considerations guide all decisions during the extraordinary experience that COVID-19 pandemic portends. The model of self-policing is acceptable and maintained principally because the citizens of any communities operate, recognize, and accept them as preferred alternatives to the official models of policing for enforcement. Hence the approach presented in this paper, which deployed existing indigenous alternative systems in ensuring compliance with COVID-19 precautionary behaviour. This article therefore documents the unique approach deployed for the containment of COVID-19 in Oyo State, Nigeria. Objective: This intervention was designed to explore established indigenous alternative systems and models of control, justice, law, security, and enforcement in Nigeria. Additionally, geographic information system (GIS) technology and investigative journalism was used to monitor and evaluate the effectiveness of the intervention. Method: The method employed was community conversation; a method of increasing inclusive, community-based engagement harnessing the expertise and motivation of key stakeholders. The community conversations were convened after the pattern of a traditional Town-hall meeting. Community conversations were organized as a qualitative framework focusing on deploying the indigenous practice of self-policing associated with Nigerias trade unions and aims to inform COVID-19 preventive behaviour at the community level. Geographical information system technology was used to develop COVID-19 Containment Compliance Citizens Reporter App. The App was developed using ESRI ArcGIS online platform to crowd source public feedback on compliance or contravention of COVID-19 protocols. Social media platforms were also deployed for monitoring and evaluation of the intervention post townhall meeting. Results: The establishment of a State-wide Containment response network provided the required inroad for advocacy and deployment of state-wide community conversation framework in the different communities comprising diverse ethnic groups, religious leaders, market leaders, National Union of Road Transport Workers (NURTW), and so on. Testimonials from the various communities showed that the people have embraced the self-policing strategy and the network system was effective with good outcomes in terms of response to decontamination, containment, and advocacy. The COVID-19 Containment Compliance Citizens Reporter App, investigative reporting by mass media were highly effective tools for monitoring and evaluation of the outcome of the intervention as well as possible evidence for melting out incentive and disincentive measures as necessary. This approach is a template, which could be adapted and replicated in other parts of Nigeria and other African societies with similar structures, demographics, and indigenous practices.

Abstract The placenta is vital to embryonic development and requires a finely-tuned pattern of gene expression, achieved in part by its unique epigenetic landscape. Piwi-interacting RNAs (piRNAs) are a class of small-non-coding RNA with established roles as epigenetic regulators of gene expression, largely via methylation of targeted DNA sequences. The expression of piRNAs have mainly been described in germ cells, but a fraction have been shown to retain expression in adult somatic tissues. To aid in understanding the contribution of these regulators in the placenta, we provide the first description of the piRNA transcriptome in human placentas. We find 297 piRNAs to be preferentially expressed in the human placenta, a subset of which are expressed at higher levels relative to testes samples. We also observed a large proportion of placental piRNAs to be expressed from a single locus, as distinct from canonical cluster locations associated with transposable element silencing. Finally, we find that 15 of the highest-expressed placental piRNAs maps to the DLK1-DIO3 locus, suggesting a link to placental biology. Our findings suggest that piRNAs could contribute to the molecular networks defining placental function in humans, and a biological impact of piRNA expression beyond germ cells.

Measurement(s) small non-coding RNA Technology Type(s) small RNA sequencing assay Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14233229

Abstract Background There is a growing number of randomized controlled trials (RCTs) evaluating interventions to prevent or treat delirium in the intensive care unit (ICU). Efforts to improve the conduct of delirium RCTs are underway, but none address issues related to statistical analysis. The purpose of this review is to evaluate heterogeneity in the design and analysis of delirium outcomes and advance methodological recommendations for delirium RCTs in the ICU. Methods Relevant databases, including PubMed and Embase, were searched with no restrictions on language or publication date; the search was conducted on July 8, 2019. RCTs conducted on adult ICU patients with delirium as the primary outcome were included where trial results were available. Data on frequency and duration of delirium assessments, delirium outcome definitions, and statistical methods were independently extracted in duplicate. The review was registered with PROSPERO (CRD42020141204). Results Among 65 eligible RCTs, 44 (68%) targeted the prevention of delirium. The duration of follow-up varied, with 31 (48%) RCTs having ≤7 days of follow-up, and only 24 (37%) conducting delirium assessments after ICU discharge. The incidence of delirium was the most common outcome (50 RCTs, 77%) for which 8 unique statistical methods were applied. The most common method, applied to 51 of 56 (91%) delirium incidence outcomes, was the two-sample test comparing the proportion of patients who ever experienced delirium. In the presence of censoring of patients at ICU discharge or death, this test may be misleading. The impact of censoring was also not considered in most analyses of the duration of delirium, as evaluated in 24 RCTs, with 21 (88%) delirium duration outcomes analyzed using a non-parametric test or two-sample t test. Composite outcomes (e.g., rank-based delirium- and coma-free days), used in 11 (17%) RCTs, seldom explicitly defined how ICU discharge, and death were incorporated into the definition and were analyzed using non-parametric tests (11 of 13 (85%) composite outcomes). Conclusions To improve delirium RCTs, outcomes should be explicitly defined. To account for censoring due to ICU discharge or death, survival analysis methods should be considered for delirium incidence and duration outcomes; non-parametric tests are recommended for rank-based delirium composite outcomes. Trial registration PROSPERO CRD42020141204 . Registration date: 7/3/2019.

Abstract Background The primary prevention of cardiovascular (CV) events is often less intense in persons at higher CV risk and vice versa. Clinical practice guidelines recommend that clinicians and patients use shared decision making (SDM) to arrive at an effective and feasible prevention plan that is congruent with each person’s CV risk and informed preferences. However, SDM does not routinely happen in practice. This study aims to integrate into routine care an SDM decision tool (CV Prevention Choice) at three diverse healthcare systems in the USA and study strategies that foster its adoption and routine use. Methods This is a mixed method, hybrid type III stepped wedge cluster randomized study to estimate (a) the effectiveness of implementation strategies on SDM uptake and utilization and (b) the extent to which SDM results in prevention plans that are risk-congruent. Formative evaluation methods, including clinician and stakeholder interviews and surveys, will identify factors likely to impact feasibility, acceptability, and adoption of CV Prevention Choice as well as normalization of CV Prevention Choice in routine care. Implementation facilitation will be used to tailor implementation strategies to local needs, and implementation strategies will be systematically adjusted and tracked for assessment and refinement. Electronic health record data will be used to assess implementation and effectiveness outcomes, including CV Prevention Choice reach, adoption, implementation, maintenance, and effectiveness (measured as risk-concordant care plans). A sample of video-recorded clinical encounters and patient surveys will be used to assess fidelity. The study employs three theoretical approaches: a determinant framework that calls attention to categories of factors that may foster or inhibit implementation outcomes (the Consolidated Framework for Implementation Research), an implementation theory that guides explanation or understanding of causal influences on implementation outcomes (Normalization Process Theory), and an evaluation framework (RE-AIM). Discussion By the project’s end, we expect to have (a) identified the most effective implementation strategies to embed SDM in routine practice and (b) estimated the effectiveness of SDM to achieve feasible and risk-concordant CV prevention in primary care. Trial registration ClinicalTrials.gov, NCT04450914 . Posted June 30, 2020 Trial status This study received ethics approval on April 17, 2020. The current trial protocol is version 2 (approved February 17, 2021). The first subject had not yet been enrolled at the time of submission.

Bacterial biofilm is a complex community of microbes that contributes to the formation of bacterial resistance to adverse environmental factors. Detection and analysis of biologically active compounds indicative of biofilm development is a promising direction in the diagnosis of biofilm formation. This paper describes the possibility of detecting surface changes in Pseudomonas bacteria when they change from planktonic to biofilm form. These surface changes were detected through the conformational changes in the outer membrane components, including lipopolysaccharide (LPS). The electrophysical profile of the same strain differed largely between planktonic and biofilm cultures. The monosaccharide and fatty acid composition and the electrophoretic mobility of cell surface LPS and the biofilm matrix polysaccharides of P. putida TSh-18 were characterized. In the LPS of biofilm cells, rhamnose and glucose residues prevailed; in the biofilm matrix polysaccharides, rhamnose, mannose, and glucose residues prevailed. The fatty acid composition of the LPS of biofilms was similar to that of the LPS of planktonic cells. The biofilms contained both S- and R-form LPS. The results are promising for the development of an electrical sensor method for the rapid in vitro diagnostics of the initial phase of bacterial biofilm formation and timely blocking of biofilm communities.

During airway branching morphogenesis, focal regions of FGF-10 expression in the pulmonary mesenchyme are thought to provide a local guidance cue, which promotes chemotactically the directional outgrowth of the airway epithelium. Here, however, we show that an ectopic source of FGF-10 induces epithelial buckling morphogenesis and the formation of multiple new supernumerary buds. FGF-10-induced budding can be modulated by altered epithelial tension and luminal fluid pressure. Increased tension suppresses the formation of ectopic branches, while a collapse of the embryonic airway promotes more expansive buckling and additional FGF-10-induced supernumerary buds. Our results indicate that a focal source of FGF-10 can promote epithelial buckling and suggest that the overall branching pattern cannot be explained entirely by the templated expression of FGF-10. Both FGF-10-mediated cell behaviors and exogenous mechanical forces must be integrated to properly shape the bronchial tree.

BackgroundOsteogenesis imperfecta (OI) is a rare heterogeneous genetic disorder commonly autosomal dominant with variants in the COL1A1 and COL1A2 genes. It is characterized by bone fragility and deformity, recurrent fractures, blue sclera, dentinogenesis imperfecta, short stature, and progressive deafness.Case presentationWe present a novel splicing mutation in the COL1A1 gene (c.2398-1G > C) in a 6-year-old Ecuadorian girl with fractures after light pressure and blue sclera. We identified the pathogenic variant, performed a literature review of splice variants, and recognized their location in the COL1A1 functional domains.ConclusionWe describe the first clinical description of a patient with OI type 1 caused by a splice variant in intron 34 of COL1A1 gene and identify that most of them are localized in the triple-helical region domain. We suggest that the splice variant in signal peptide, von Willebrand factor type C, and nonhelical regions maintain their functionality or that individuals affected with severe cases die early in development and are not reported.

Thermal expansion of refractory ceramics CaZrO3, MgAl2O4, La2Zr2O7 and YSZ-12 was studied. The samples of the complex oxides were synthesized by solution combustion synthesis with glycine; the fuel:oxidant ratio was varied depending on the character of redox reaction. The linear thermal expansion coefficient (LTEC) of ceramics was measured on the samples with an initial density 23–52%. The maximal sinterability of 89–92% after 6 h annealing at 1550 °С was demonstrated by La2Zr2O7 and YSZ-12, and the minimal values (78–82%) – by CaZrO3 and MgAl2O4. All materials have close LTEC values, from 9.0 to 9.6·10–6 K–1.

Salivary glands are vital structures responsible for successful tick feeding. The saliva of ticks contains numerous active molecules that participate in several physiological processes. A Kunitz-type factor Xa (FXa) inhibitor, similar to the tissue factor pathway inhibitor (TFPI) precursor, was identified in the salivary gland transcriptome of Amblyomma sculptum ticks. The recombinant mature form of this Kunitz-type inhibitor, named Amblyomin-X, displayed anticoagulant, antiangiogenic, and antitumor properties. Amblyomin-X is a protein that inhibits FXa in the blood coagulation cascade and acts via non-hemostatic mechanisms, such as proteasome inhibition. Amblyomin-X selectively induces apoptosis in cancer cells and promotes tumor regression through these mechanisms. Notably, the cytotoxicity of Amblyomin-X seems to be restricted to tumor cells and does not affect non-tumorigenic cells, tissues, and organs, making this recombinant protein an attractive molecule for anticancer therapy. The cytotoxic activity of Amblyomin-X on tumor cells has led to vast exploration into this protein. Here, we summarize the function, action mechanisms, structural features, pharmacokinetics, and biodistribution of this tick Kunitz-type inhibitor recombinant protein as a promising novel antitumor drug candidate.

Clostridioides difficile infection is an increasing presence worldwide. Prevention is multipronged, reflecting a complex and evolving epidemiology. Multiple guidelines exist regarding the prevention of C. difficile infection in healthcare settings; however, existing guidelines do not address C. difficile in low- and middle-income countries (LMIC). Nevertheless, the prevalence of C. difficile in LMIC likely parallels, if not exceeds, that of high-income countries, and LMIC may experience additional challenges in C. difficile diagnosis and control. A panel of experts was convened by the International Society for Infectious Diseases (ISID) to review the current state of C. difficile infections globally and make evidence-based recommendations for infection prevention that are broadly applicable.

Reducing dietary CP for broiler chickens below a certain threshold results in decreased growth, even when the supply of essential amino acids and glycine equivalent (Glyequi) is adequate, probably because other nonessential amino acids (neAA) are growth-limiting. Nonprotein nitrogen (NPN) might be used for the synthesis of neAA. Therefore, the effects of specific neAA and ammonium chloride (NH4Cl) supplementation on the growth and N-excretion characteristics of broiler chickens were investigated. Nine male Ross 308 broiler chickens were kept in each of 81 metabolism units from day 7 to 21 and received 1 of 9 diets in 9 replicates in a one-factorial arrangement of treatments. Two diets with different neAA concentrations, except for Glyequi, were mixed resulting in CP levels of 180 (CP180) and 160 (CP160) g/kg. In six other diets, CP160 was supplemented with either l-Ala, l-Pro, l-Asp, a mix of l-Asp and l-Asn·H2O, l-Glu, or a mix of l-Glu and l-Gln to achieve concentrations of the respective neAA as formulated in CP180. In a further diet, NH4Cl was added to CP160 to achieve the CP concentration of CP180. The ADG and gain:feed ratio (G:F) from day 7 to 21 were highest at CP180. Reduced neAA concentrations in CP160 decreased ADG and G:F. Supplementation of Asp+Asn, Glu, and Glu+Gln to CP160 increased ADG and G:F, but not to the level found for CP180. Compared with CP160, addition of Asp increased G:F but not ADG. Supplementation of Asp+Asn caused higher ADG and G:F than supplementation of Asp alone. The N-utilization efficiency was highest at CP160 and at CP160 supplemented with Ala, Pro, and Glu. Lower N-utilization efficiency was found at CP180 than at CP160, without and with supplemented neAA. The treatment containing NH4Cl presented the lowest ADG, G:F, and N-utilization efficiency. These results showed that individual supplementation of Asp+Asn, Glu, and Glu+Gln partly compensates for the growth-reducing effects of very low CP diets. Supplementation of NH4Cl as NPN source is not suitable for broiler chickens.

Surgical site infection (SSI) rates in low- and middle-income countries (LMICs) range from 8 to 30% of procedures, making them the most frequent healthcare-acquired infection (HAI) with substantial morbidity, mortality, and economic impacts. Presented here is an approach to surgical site infection prevention based on surveillance and focused on five critical areas identified by international experts. These five areas include1. Collecting valid, high-quality data;2. Linking HAIs to economic incapacity, underscoring the need to prioritize infection prevention activities;3. Implementing SSI surveillance within infection prevention and control (IPC) programs to enact structural changes, develop procedural skills, and alter healthcare worker behaviors;4. Prioritizing IPC training for healthcare workers in LMICs to conduct broad-based surveillance and to develop and implement locally applicable IPC programs; and5. Developing a highly accurate and objective international system for defining SSIs, which can be translated globally in a straightforward manner.Finally, we present a clear, unambiguous framework for successful SSI guideline implementation that supports developing sustainable IPC programs in LMICs. This entails1. Identifying index operations for targeted surveillance;2. Identifying IPC “champions” and empowering healthcare workers;3. Using multimodal improvement measures;4. Positioning hand hygiene programs as the basis for IPC initiatives;5. Use of telecommunication devices for surveillance and healthcare outcome follow-ups.Additionally, special considerations for pediatric SSIs, antimicrobial resistance development, and antibiotic stewardship programs are addressed.

Global sustainability rests on a myriad of benefits provided by natural ecosystems that support human livelihoods and well-being, from biodiversity persistence to climate regulation. The undeniable importance of conserving tropical forests has drawn most of the conservation spotlight towards it. However, open ecosystems such as the Brazilian Campo Rupestre (rupestrian grassland), have been historically overlooked despite their high diversity and key associated ecosystem services. We highlight major current threats to the persistence of the Campo Rupestre emphasizing its ecological, social, cultural, geo-environmental, and economic importance. We call attention to the importance of the Campo Rupestre as a reservoir of biodiversity and ecosystem services and offer priority actions that resulted from discussions involving scientists, industry representatives, environmental managers, and other members of civil society. Proposed actions include efforts related to ecological restoration, sustainable ecotourism, protection of traditional ecological knowledge, identification of emerging research questions, and development of tailored public policies. Such issues are integrated into a framework that collectively represents a road map to safeguard the Campo Rupestre from further degradation and steer its historical overexploitation towards sustainable management. Safeguarding the future of non-forest biomes like this poses a challenge to current paradigms of nature conservation. By establishing priorities and guidelines, we propose an actionable plan, which we hope can support informed decision-making policy towards a sustainable use of the Campo Rupestre.

Following injury and refractive surgery, corneal wound healing can initiate a protracted fibrotic response that interferes with ocular function. This fibrosis is related, in part, to the myofibroblast differentiation of corneal keratocytes in response to transforming growth factor beta 1 (TGF-β1). Previous studies have shown that changes in the mechanical properties of the extracellular matrix (ECM) can regulate this process, but the mechanotransductive pathways that govern stiffness-dependent changes in keratocyte differentiation remain unclear. Here, we used a polyacrylamide (PA) gel system to investigate how mechanosensing via focal adhesions (FAs) regulates the stiffness-dependent myofibroblast differentiation of primary corneal keratocytes treated with TGF-β1. Soft (1 kPa) and stiff (10 kPa) PA substrata were fabricated on glass coverslips, plated with corneal keratocytes, and cultured in defined serum free media with or without exogenous TGF-β1. In some experiments, an inhibitor of focal adhesion kinase (FAK) activation was also added to the media. Cells were fixed and stained for F-actin, as well as markers for myofibroblast differentiation (α-SMA), actomyosin contractility phosphorylated myosin light chain (pMLC), focal adhesions (vinculin), or Smad activity (pSmad3). We also used traction force microscopy (TFM) to quantify cellular traction stresses. Treatment with TGF-β1 elicited stiffness-dependent differences in the number, size, and subcellular distribution of FAs, but not in the nuclear localization of pSmad3. On stiff substrata, cells exhibited large FAs distributed throughout the entire cell body, while on soft gels, the FAs were smaller, fewer in number, and localized primarily to the distal tips of thin cellular extensions. Larger and increased numbers of FAs correlated with elevated traction stresses, increased levels of α-SMA immunofluorescence, and more prominent and broadly distributed pMLC staining. Inhibition of FAK disrupted stiffness-dependent differences in keratocyte contractility, FA patterning, and myofibroblast differentiation in the presence of TGF-β1. Taken together, these data suggest that signaling downstream of FAs has important implications for the stiffness-dependent myofibroblast differentiation of corneal keratocytes.

Dysregulation of ubiquitin-proteasome pathway genes through copy number alteration, promoter hypomethylation, and miRNA deregulation is involved in cancer development and progression. Further characterizing alterations in these genes may uncover novel drug targets across a range of diseases in which druggable alterations are uncommon, including hepatocellular carcinoma (HCC). We analyzed 377 HCC and 59 adjacent non-malignant liver tissue samples, focusing on alterations to component genes of the widely studied CRL2pVHL E3 ubiquitin ligase complex. mRNA upregulation of the component genes was common, and was correlated with DNA hypomethylation and copy number increase, but many tumours displayed overexpression that was not explained by either mechanism. Interestingly, we found 66 miRNAs, including 39 previously unannotated miRNAs, that were downregulated in HCC and predicted to target one or more CRL2pVHL components. Several miRNAs, including hsa-miR-101-3p and hsa-miR-139-5p, were negatively correlated with multiple component genes, suggesting that miRNA deregulation may contribute to CRL2pVHL overexpression. Combining miRNA and mRNA expression, DNA copy number, and methylation status into one multidimensional survival analysis, we found a significant association between greater numbers of alterations and poorer overall survival for multiple component genes. While the intricacies of CRL2pVHL complex gene regulation require additional research, it is evident that multiple causes for the deregulation of these genes must be considered in HCC, including non-traditional mechanisms.