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Rationale and objectives: High-resolution T2-weighted magnetic resonance imaging (MRI) of the pelvis is the main technique used for diagnosing benign and malignant uterine diseases. However, the procedure may be time-consuming and requires training and experience. Therefore, this study was performed to compare the image quality of standard clinical BLADE (stBLADE) with a prototypical accelerated simultaneous multi-slice (SMS) BLADE procedure with either improved temporal resolution (tr) at the same slice thickness (SL) or improved spatial resolution (sr) with the same examination time and a prototypical isotropic 3D SPACE procedure with inner-volume excitation and iterative denoising. Materials and methods: Patients who underwent clinically indicated MRI of the uterus were included in this prospective study and underwent stBLADE (acquisition time, 2 min 59 s; SL, 4 mm) and SMS BLADE (tr) with the same SL (4 mm) but reduced examination time (1 min 20 s) as well as SMS BLADE (sr) with thinner slices (3 mm) and comparable examination time (3 min 16 s). In addition, 3D SPACE was acquired in a sagittal orientation (5 min 36 s). The short axis of the cervix and the long axis of the corpus uteri were reconstructed in 1-mm and 3-mm SLs, retrospectively. Subjective overall image impression, delineation of anatomy/organs, lesion demarcation, and motion artifacts were assessed using a 5-point Likert scale and compared among the different techniques. The preferred sequence was then selected by three independent assessors. Results: The analysis was based on 38 women (mean age, 44 ± 15 years). The overall image impression was similar for stBLADE, SMS BLADE (sr), and SMS BLADE (tr) but was significantly lower for 3D SPACE than stBLADE (p = 0.01). SMS BLADE (sr) was considered the preferred sequence because of slightly better performance in terms of overall image impression, organ delineation, and lesion demarcation, but without statistical significance. Both SMS BLADE (tr) and (sr) produced significantly fewer motion artifacts than stBLADE (p < 0.01 and p = 0.01), with no significant difference between SMS BLADE (tr) and (sr), while 3D SPACE had a significantly lower rating than stBLADE (p < 0.01). Image quality was rated as the least diagnostic criterion in all sequences and all cases. Conclusion: SMS BLADE (sr) was the preferred sequence for MRI of the female pelvis, with higher sr than stBLADE. SMS BLADE (tr) may also be used to reduce the acquisition time without compromising image quality. Despite its lower image quality, 3D SPACE can also reduce the examination time and improve the workflow because of the possibility of retrospective multiplanar reconstructions., Academic Radiology, 30 (6), ISSN:18784046, ISSN:1076-6332

Languages are subject to increasingly complex market conditions. This presents opportunities and challenges for sustainable development within minority communities, given tensions between identity and profit, particularly within regional tourism. Through a social sustainability lens, this article compares the opportunities and challenges for sustainable linguistic and cultural practices across two contexts: Cornish and Silesian. It seeks to answer the extent to which these cultures are sustainable, and how their futures could look. We focus on two distinct yet broadly interrelated themes, predominantly within Cornwall and Silesia: (old and new) media and commodification. For commodification, we also integrate a dialogue on Cornish-Mexican and Silesian-Texan heritage. Whilst we see the increased presence of old media in both Silesian and Cornish, there appear to be challenges – across both contexts - in terms of new media resourcing. Whilst commodification is a dynamic present across both contexts, it seems to have accrued more momentum in Cornwall than Silesia. In diverse ways, both cultures appear to show different commodification dynamics in the Mexican and Texan overseas communities, when compared with Cornwall and Silesia. In concluding, this article poses questions around the increased visibility of small languages and cultures: how they may be made more visible without falling into the trap of misrepresenting communities’ culture(s) and language(s). Reaching across sites helps us sketch avenues for future exploration and policy innovation. The focus on sustainable growth kindled by this paper is important to empower minority communities, scope out new possibilities, and ensure long-term conservation of minority futures both within and beyond Europe.

Celem niniejszego artykułu jest przybliżenie postaci Mikołaja Zebrzydowskiego jako epistolografa. Analizie poddano listy Zebrzydowskiego zarówno niepublikowane, znajdujące się w krajowych bibliotekach i archiwach, jak również wydane drukiem. Przebadana korespondencja pochodzi z lat 1581–1615. Omówiono problematykę poruszaną w listach (zarówno informacje przekazywane bezpośrednio, jak i te ukryte w „warstwie głębokiej” tekstu), relacje z adresatami listów, język oraz styl epistoł. Tematyka korespondencji prowadzonej przez Mikołaja Zebrzydowskiego jest ściśle powiązana z jego publiczną działalnością. Jak dotąd nie udało odnaleźć się listów wojewody, które były kierowane do członków najbliższej rodziny bądź miały wyłącznie prywatny charakter. Większość listów napisanych przez Zebrzydowskiego cechuje oględność, skupienie się na konkrecie i brak rozwlekłości, co zdaje się korespondować ze skrytą i pragmatyczną naturą nadawcy. Już w korespondencji przedrokoszowej odnaleźć można ślady kontestacji poczynań Zygmunta III, które rzecz jasna przybrały na sile w latach 1606–1609. Na szczególną uwagę zasługują listy kierowane do zbiorowego adresata. W odróżnieniu od epistoł przeznaczonych do pojedynczych odbiorców, w korespondencji zwróconej do szerszej publiki wojewoda wspomina o swoich uczuciach, często odwołuje się do autorytetów, stara się poruszyć emocje czytelników, stylizuje swoje zachowanie, manipuluje faktami. By wzmocnić siłę wypowiedzi, chętnie korzysta z amplifikacji, jednego z podstawowych narzędzi w retoryce. Uznać należy, że ten typ korespondencji był jednym z ważniejszych narzędzi propagandowych stosowanych przez wojewodę.

ImportanceVenous thromboembolism (VTE) is a severe complication after free tissue transfer to the head and neck (H&N). Enoxaparin 30 mg twice daily (BID) is a common regimen for chemoprophylaxis. However, differences in enoxaparin metabolism based on body weight may influence its efficacy and safety profile.ObjectiveTo assess the association between BMI and postoperative VTE and hematoma rates in patients treated with prophylactic enoxaparin 30 mg BID.Design, Setting, and ParticipantsThis was a retrospective review of a prospectively collected cohort from 2012 to 2022. Postoperative VTE, hematoma, and free flap pedicle thrombosis were recorded within 30 days of index surgery. The setting was a tertiary academic referral center. Participants included patients undergoing H&N reconstruction with free flaps that received fixed-dose subcutaneous enoxaparin 30 mg BID postoperatively. Statistical analysis was conducted from April to May 2022.Main Outcomes and MeasuresOutcomes include incidence of VTE, hematoma, and flap pedicle thrombosis events within 30 days of the surgery. Univariate and multivariable regression models were used to evaluate associations between BMI and other patient factors with these outcomes.ResultsAmong the 765 patients included, 262 (34.24%) were female; mean (SD) age was 60.85 (12.64) years; and mean (SD) BMI was 26.36 (6.29). The rates of VTE and hematoma in the cohort were 3.92% (30 patients) and 5.09% (39 patients), respectively. After adjusting for patient factors, BMI was the only factor associated with VTE (OR, 1.07; 95% CI, 1.015-1.129). Obesity (BMI >30) was associated with increased odds of VTE (OR, 2.782; 95% CI, 1.197-6.564). Hematoma was not associated with BMI (OR, 0.988; 95% CI, 0.937-1.041). Caprini score of at least 9 was not associated with VTE (OR, 1.259; 95% CI, 0.428-3.701).Conclusions and RelevanceThis cohort study found that obesity was associated with an increased risk of VTE in patients after microvascular H&N reconstruction and while on standard postoperative chemoprophylaxis regimens. This association may suggest insufficient VTE prophylaxis in this group and a potential indication for weight-based dosing.

The adoption of improved technologies in agriculture has been shown to improve incomes, reduce poverty and contribute to rural development in many developing nations. In Togo, the Agricultural Sector Support Project (PASA) assists smallholder farmers in the adoption of the Improved Technology in Traditional Poultry Farming (ITTPF) in rural areas as a means of increasing smallholder incomes, enhancing food security and reducing poverty. However, the adoption rate is currently below expectations, especially given the promise it holds not only from an economic perspective but also from a broad environmental sustainability viewpoint since poultry manure can be used as a necessary input in smallholder farms. In this study, we examine the factors associated with the participation of farmers in PASA for the adoption of ITTPF in Togo. Our analysis covers 400 smallholder households in the 23 districts of Togo and employs Logit model with Probit model as robustness check. We find different socio-economic constraints and enablers of participation in PASA. Particularly, level of education, household size, membership in cooperative societies, hatching rate of eggs, farm size, average annual sale of poultry and self-financing capacity were positively and significantly related to the participation of farmers in PASA. The findings are robust to alternative specifications such as Probit model. Based on the findings, we argue that participation in agricultural innovation and development programs depends on the information accessible to farmers. One medium to improve information access could be agricultural cooperatives and extension services since they provide informal education, training, and access to productive inputs for farming and marketing purposes. Our findings suggest the need for agricultural policies which promote farmer organizations such as agricultural cooperatives coupled with effective extension services to enable the adoption of improved agricultural technologies.

Background/Aim: The aim was to evaluate the effect of a combined precision matrix and high sampling rate on the delineation of anatomical structures and objective image quality in single source CT in a qualitative approach. Materials and Methods: An anthropomorphic thoracic phantom was used to evaluate the objective image quality parameters, including image noise, noise power spectrum, image stepness and Q for different CT scanners including high/ standard matrix and framing frequency setups. Scan parameters were standardized over all scanners. Additional subjective quality assessment was also performed. Results: A linear mixed effects model was used to determine the effect of sampling rate and image matrix on objective image quality parameters. Noise power spectrum and image noise were significantly influenced by both framing frequency and image matrix. There were significant differences between high and standard frequency/ matrix acquisitions. Conclusion: Higher framing frequency and image matrix allows for improved image noise texture and objective image quality in CT.

Este paper tem como principal objetivo avaliar brevemente a importância da OMC na liberalização do comércio internacional, a partir da observação de sua atuação no caso das Terras Raras. Para tanto, será feita uma breve descrição acerca do das tratativas envolvendo a atuação do OMC, mais especificamente no que diz respeito ao Mecanismo de Solução de Controvérsias, que tem sido utilizado pela China no que diz respeito ao caso da atividade mineral das chamadas Terras Raras. A despeito dos recentes acontecimentos na realidade internacional, há evidências no sentido de afirmar a adequação das atividades da organização relativamente a seus propósitos se manifestam claramente no caso em questão, fortalecendo o papel da OMC na promoção de um comércio internacional mais livre e equilibrado.

The process of epithelial-mesenchymal transition (EMT) occurs in both physiological and pathological states, and there are increasing links between EMT and tumor progression. During this process, dynamic changes in cell organization and function occur that promote migration and invasion. A better understanding of the mechanism of plastic EMT may help develop novel targeted therapies that can help treat cancers of varying degrees of malignancy. Our review helps to systematize knowledge of the molecular and biochemical mechanisms involved in the EMT process in both tumor and physiological backgrounds.

W ostatnich latach obserwuje się dynamiczny rozwój laboratoryjnych metod nieniszczących przeznaczonych do badań własności skał. Należy do nich metoda rentgenowskiej tomografii komputerowej (CT), dająca możliwość wizualizacji wewnętrznej przestrzeni porowej skał bez naruszenia ich struktury. W pracy pokazano zastosowanie metody CT w skałach charakteryzujących się znacznym zróżnicowaniem przestrzeni porowej. Zmienność ta związana jest z występowaniem dużej ilości nieregularnie rozmieszczonych porów i kawern oraz szczelin o różnym stopniu wypełnienia. W ramach pracy wykonano obrazowanie przestrzeni porowej wraz z podziałem na porowatość szczelinową i kawernistą dla wybranych fragmentów rdzeni obejmujących wapienie, anhydryty i zlepieńce. Badania przeprowadzono z rozdzielczością 0,130 mm. Na ich podstawie uzyskano wartości porowatości dla metrowych odcinków rdzeni wiertniczych oraz dla wybranych fragmentów rdzenia. W przypadku anhydrytu podział na porowatość związaną z porami (0,18%) i porowatość kawernistą (0,26%) świadczy o stosunkowo dużej zawartości większych pustek w skale, co prawdopodobnie jest związane z rozpuszczaniem soli. Analiza dwóch fragmentów rdzenia wapienia uwidoczniła dużą zmienność struktury przestrzeni porowej. Na porowatość górnego fragmentu składa się, w największym stopniu, porowatość związana z drobnymi pustkami (1,79%). Porowatość pochodząca od kawern to 1,09%, natomiast porowatość szczelinowa stanowi najmniejszy procent porowatości całkowitej i wynosi 0,41%. Porowatość dolnego fragmentu rdzenia jest znacznie niższa. Składają się na nią głównie pory (0,42%) oraz w mniejszym stopniu kawerny (0,25%), natomiast porowatość szczelinowa stanowi zaledwie 0,05%. Porowatość zlepieńca jest bardzo niska (0,29%) i obejmuje głównie drobne pory i kawerny. Zastosowana metoda rentgenowskiej tomografii komputerowej pozwoliła na rozszerzenie charakterystyki przestrzeni porowej w badanych skałach i otrzymanie pełniejszej informacji na temat rozkładu porów, kawern i szczelin w rdzeniach.

Qualitative NMR spectroscopic and quantitative calorimetric binding studies were performed to characterize the interaction of nontoxic mimics of the V-type nerve agent VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate) and the Novichok nerve agent A-234 (ethyl (1-(diethylamino)ethylidene)phosphoramidofluoridate) with a series of receptors in 100 mM aqueous phosphate buffer at pH 7.4 and 37 °C. These investigations provided information about the preferred geometry with which the nerve agent mimics are included into the receptor cavities and about the stability of the complexes formed. According to the results, the positively charged VX mimic prefers to bind to cation receptors such as sulfonated calixarenes and an acyclic cucurbituril but does not noticeably interact with cyclodextrins. While binding to the acyclic cucurbituril is stronger than that to calixarenes, the mode of inclusion into the sulfonatocalix[4]arene cavity is better suited for the development of scavengers that bind and detoxify V-type nerve agents. The neutral Novichok mimic, on the other hand, only interacts with the acyclic cucurbituril with a strength required for scavenger development. These binding studies thus provided guidelines for the further development of nerve agent scavengers.

Niniejsza praca została poświęcona kompleksowej interpretacji interwałów otworu wiertniczego B-7, w przypadku którego dysponowano rdzeniami zbudowanymi z takich skał jak anhydryty, dolomity, węglany oraz mułowce. Do przeprowadzenia badań wykorzystane zostały dane uzyskane na podstawie ciągłych pomiarów rdzeni wiertniczych z zastosowaniem metod tomografii komputerowej (CT), fluorescencji rentgenowskiej (XRF) oraz naturalnej promieniotwórczości gamma (GR) wraz z pomiarem gęstości objętościowej (gamma-gamma). Wymienione metody wchodzą w zakres pomiarów nieniszczących; z wykorzystaniem odpowiednich kalibracji mogą być prowadzone na połówkach rdzeni archiwalnych. Dla uzyskania szczegółowej interpretacji profilowań rdzeni wiertniczych wymagane jest wykonanie laboratoryjnych pomiarów referencyjnych. W przypadku rdzeni z otworu B-7 badania laboratoryjne przeprowadzono na próbkach pobranych z roboczej części rdzenia. Zakres badań stacjonarnych obejmował pomiary składu chemicznego (ICP-MS/OES), mineralnego (XRD), promieniotwórczości naturalnej gamma (K, U, Th), gęstości objętościowej oraz porowatości. Wyniki pomiarów laboratoryjnych posłużyły do sprawdzenia jakości danych oraz do kalibracji ciągłych pomiarów rdzeni w postaci połówek walca (część archiwalna). Na podstawie skalibrowanych danych XRF i badań XRD utworzono modele mineralogiczno-chemiczne dla skał anhydrytowych, węglanowych i mułowcowych, dzięki którym przeprowadzono interpretację litologiczną. Badania gęstości i porowatości posłużyły do kalibracji krzywych gęstości uzyskanych z metody gamma-gamma oraz CT. W ramach kompleksowej interpretacji danych geofizycznych wyniki z ciągłych pomiarów rdzeni zostały porównane z profilowaniami geofizyki wiertniczej oraz z wynikami badań laboratoryjnych. Łącznie przebadano około 28 metrów rdzeni wiertniczych. Ponadto wykonano zestawienie wyników interpretacji litologicznej z pomiarów otworowych, jak i pomiarów na rdzeniach. Końcowe zestawienia zaprezentowano w postaci krzywych wynikowych oraz słupków litologicznych w domenie głębokości. Wybrane interwały rdzeni pozwoliły na przetestowanie stosowanej aparatury oraz metod interpretacji w szerokim zakresie zmienności litologicznej.

MEMS technology has made sensors for measuring barometric pressure and altitude above sea level very cheap and widely used in many consumer electronic devices. This paper presents a theoretical analysis of the sources and types of errors in the barometric altimeter using the standard atmosphere model (ISA). Methods for correcting principal errors caused by non-standard sea level conditions are described and compared. A method of correcting errors in the case of altimeter horizontal movement to the air column and total pressure measurement was proposed. It was compared with another method known from the literature. In the numerical experiment, data recorded by a bicycle computer equipped with a MEMS-based barometric altimeter was analyzed. As the GPS data of the route covered was also known, it was possible to compare the recorded altimeter data with the heights determined from the digital terrain model (DTM), which in this case were considered accurate. The error of the measured altitude calculated in this way was tried to be divided into the principal error, the external error caused by the sensor movement, and the barometer drift. Hence, a numerical experiment was carried out in which, based on the recorded data, an attempt was made to reconstruct non-standard sea level conditions and the impact of speed on the sensor measurements. Furthermore, a method of solving such a reverse problem was proposed. The results of the presented studies can be used in the design of systems correcting the indications of barometric altimeters. The accuracy of the altitude measurement is especially important for small controlled flying objects (UAH) and when recording the route of vehicles moving on the ground.

WstępCOVID-19 (coronavirus disease 2019), choroba wywołana infekcją SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), może charakteryzować się mniej lub bardziej nasilonym przebiegiem. Celem niniejszego opracowania była analiza objawów, jakie wystąpiły w grupie osób z dodatnim wynikiem testu na obecność materiału genetycznego wirusa.Materiał i metodyAnalizę przeprowadzono na podstawie wyników ankiety przeprowadzonej wśród 337 polskich pacjentów – 185 (55%) kobiet oraz 152 (45%) mężczyzn w wieku 18–86 lat. Kwestionariusz zawierał 26 pytań, z czego 11 dotyczyło objawów ogólnoustrojowych. Określono częstość ich występowania oraz nasilenie w skali VAS (Visual Analogue Scale).WynikiDo najczęstszych objawów, występujących u ponad 50% ankietowanych, należą: ogólne osłabienie (91% ankietowanych, nasilenie 6,25 w skali VAS), bóle układu mięśniowo-szkieletowego (77%, VAS 5,67), bóle głowy (65%, VAS 5,37) oraz kaszel (56%, VAS 4,76). Chorobie rzadziej towarzyszyły katar, gorączka powyżej 38°C oraz bóle gardła, które wystąpiły u 39% pacjentów. Najrzadziej występowały biegunka (23%), zmiany skórne (7%) oraz wymioty (3%). Określając współczynnik korelacji, stwierdzono również, iż duszności występowały najczęściej z ogólnym osłabieniem (r = 1), natomiast rzadziej ogólnemu osłabieniu towarzyszyły bóle mięśniowo-szkieletowe (r = 0,8). Nie stwierdzono statystycznie istotnych zależności między częstością występowania danych objawów a wiekiem, płcią czy chorobami współistniejącymi u ankietowanych.WnioskiObserwacje wykazały, iż w analizowanej grupie zakażonych SARS-CoV-2 choroba miała przebieg łagodny lub umiarkowany. Najczęstszymi objawami były: ogólne zmęczenie, bóle mięśniowo-szkieletowe, kaszel oraz objawy nieżytu górnych dróg oddechowych.

Wear is one of the decisive factors for the economic efficiency of sheet metal forming processes. Thereby, progressive wear phenome lead on the one hand to a poor workpiece quality and on the other hand to tool failure resulting in high machine downtimes. This trend is intensified by processing high-strength materials and the reduction of lubricant up to dry forming. In this context, data-driven monitoring methods such as machine learning (ML) provide the potential of detecting wear at an early stage to overcome manual and cost-intensive process inspections. The presented study aims to provide a ML based inline quantification of wear states within sheet metal forming processes. The development of this monitoring approach is based on a procedure model the Knowledge Discovery in Time series and image data in Engineering Epplications (KDT-EA) which is validated on two forming processes, blanking and roll forming, that strongly differ in their physical process behavior and their acquired process data. The presented inline quantification allows an estimation of wear states with a deviation of less than 0.83% for the blanking process and 2.21% for the roll forming process from the actual wear state. Furthermore, it is shown that combining different feature extraction methods as well as a compensation of unbalanced data using data augmentation techniques are able to improve the performance of the investigated ML models.

We present a new analysis of previously published SuperCDMS data using a profile likelihood framework to search for sub-GeV dark matter (DM) particles through two inelastic scattering channels: bremsstrahlung radiation and the Migdal effect. By considering these possible inelastic scattering channels, experimental sensitivity can be extended to DM masses that are undetectable through the DM-nucleon elastic scattering channel, given the energy threshold of current experiments. We exclude DM masses down to 220 MeV/c2 at 2.7×10−30 cm2 via the bremsstrahlung channel. The Migdal channel search provides overall considerably more stringent limits and excludes DM masses down to 30 MeV/c2 at 5.0×10−30 cm2.

Recently, thanks to the greater discovery of the mechanisms of facial aging, an alternative to invasive plastic surgery has found space with less invasive aesthetic procedures, also based on an increasingly pressing request. We are specifically referring to dermal filler injection into or under the skin which leads to immediate rejuvenation and aesthetic improvements. In this study, we wanted to analyze the results obtained through the use of NEAUVIA Organic Stimulate, particularly with regard to its effectiveness, which is a cross-linked polymeric hydrogel, containing stabilized sodium hyaluronate 26 mg/mL and calcium hydroxyapatite (1%), glycine and L-proline in buffer pyrogen-free water, in its main indication, namely, the temporary correction of congenital and acquired deficiencies of the soft tissues of the face by intradermal injection. Initially, 70 patients were enrolled, but 10 did not complete the study due to non-observance of the investigation rules, so they were excluded from the protocol. The collected data demonstrate an efficient mechanical effect of the pegylated polymeric acid matrix enriched with low concertation of calcium hydroxyapatite and in accordance with other evidence in vitro and in vivo, and the mechanical support of the interstitial connective space improves the homestays of the anatomical layer rebalancing the physiological activity of the dermis cells.

The use of data and algorithms in the social sciences allows for exciting progress, but also poses epistemological challenges. Operations that appear innocent and purely technical may profoundly influence final results. Researchers working with data can make their process less arbitrary and more accountable by making theoretically grounded methodological choices. We apply this approach to the problem of simplifying networks representing ethnographic corpora, in the interest of visual interpretation. Network nodes represent ethnographic codes, and their edges the co-occurrence of codes in a corpus. We introduce and discuss four techniques to simplify such networks and facilitate visual analysis. We show how the mathematical characteristics of each one are aligned with an identifiable approach in sociology or anthropology: structuralism and post-structuralism; identifying the central concepts in a discourse; and discovering hegemonic and counter-hegemonic clusters of meaning. We then provide an example of how the four techniques complement each other in ethnographic analysis.

Background Despite the wide variety of Next Generation Sequencing (NGS)-based methods, it remains challenging to detect mutations present at very low frequencies. This problem is particularly relevant in oncology, where the limiting amount of input material, and its low quality, often limit the performance of the assays. Unique Molecular Identifiers (UMIs) are a molecular barcoding system often coupled with computational methods of noise suppression to improve the reliability of detection of rare variants. Although widely adopted, UMI inclusion imposes additional technical complexity and sequencing cost. Currently, there are no guidelines on UMI usage nor a comprehensive evaluation of their advantage across different applications. Methods We used DNA sequencing data generated by molecular barcoding and hybridization-based enrichment, from various types and quantities of input material (fresh frozen, formaldehyde-treated and cell-free DNA), to evaluate the performance of variant calling in different clinically relevant contexts. Results Noise suppression achieved by read grouping based on fragment mapping positions ensures reliable variant calling for many experimental designs even without exogenous UMIs. Exogenous barcodes significantly improve performance only when mapping position collisions occur, which is common in cell-free DNA. Conclusions We demonstrate that UMI usage is not universally beneficial across experimental designs and that it is worthwhile to critically consider the comparative advantage of UMI usage for a given NGS application prior to experimental design.

Background: Parkinson’s disease (PD) is a neurodegenerative disorder that is characterized by the presence of proteinaceous alpha-synuclein (α-syn) inclusions (Lewy bodies), markers of neuroinflammation and the progressive loss of nigrostriatal dopamine (DA) neurons. These pathological features can be recapitulated in vivo using the α-syn preformed fibril (PFF) model of synucleinopathy. We have previously described the time course of microglial major-histocompatibility complex-II (MHC-II) expression and alterations in microglia morphology in the PFF model in rats. Specifically, the peaks of α-syn inclusion formation, MHC-II expression, and reactive morphology in the substantia nigra pars compacta (SNpc) all occur two months post PFF injection, months before neurodegeneration occurs. These results suggest that activated microglia may contribute to neurodegeneration and could represent a potential target for novel therapeutics. The goal of this study was to determine whether microglial depletion could impact the magnitude of α-syn aggregation, nigrostriatal degeneration, or related microglial activation during the α-syn PFF model. Methods: Male Fischer 344 rats were injected intrastriatally with either α-syn PFFs or saline. Rats were continuously administered Pexidartinib (PLX3397B, 600mg/kg), a colony stimulating factor-1 receptor (CSF1R) inhibitor, to deplete microglia for a period of either two or six months. Results: PLX3397B administration resulted in significant depletion (45-53%) of ionized calcium-binding adapter molecule 1 immunoreactive (Iba-1ir) microglia within the SNpc. Microglial depletion did not impact accumulation of phosphorylated α-syn (pSyn) within SNpc neurons and did not alter pSyn associated microglial reactivity or expression of MHC-II. Further, microglial depletion did not impact SNpc neuron degeneration. Paradoxically, long term microglial depletion resulted in increased soma size of remaining microglia in both control and PFF rats, as well as expression of MHC-II in extranigral regions. Conclusions: Collectively, our results suggest that microglial depletion is not a viable disease-modifying strategy for PD and that partial microglial depletion can induce a heightened proinflammatory state in remaining microglia.

This article examines the anti-Lukashenka protest movement in Belarus by comparing it to the Solidarity movement in Poland. We organize our analysis around the concept of four stages identifiable in the development of social movements: emergence, coalescence, bureaucratization, and decline. We argue that protests in Belarus reached the bureaucratization stage, but their transformation into a more durable movement was slowed down by the brutal repressions unleashed by the Lukashenka regime propped up by Putin’s Russia. However, the spectacular changes in people’s conceptions of national identity built around symbols different from those associated with the officialdom may sustain emotional mobilization necessary for formation of higher levels of organizations in the oppressive context of today’s Belarus. The contours of this process are brought into sharp relief when compared with the long, cumulative trajectory of the 1956-89 anti-authoritarian Polish revolts. This opens the way for cautious prognostication.

This study aimed to compare the historical incidence rate of severe oral mucositis (OM) in head and neck cancer patients undergoing definitive concurrent chemoradiation therapy (CRT) versus a prospective cohort of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with prophylactic photobiomodulation therapy (PBMT).This US-based, institutional, single-arm, phase Ⅱ prospective clinical trial was initiated in 50 patients (age ≥ 18 years, Karnofsky Performance Scale Index 60, with locally advanced HNSCC (excluding oral cavity) receiving definitive or adjuvant radiation therapy (RT) with concurrent platinum-based chemotherapy (CT). PBMT was delivered three times per week throughout RT utilizing both an intraoral as well extraoral delivery system. Primary outcome measure was incidence of severe OM utilizing both the National Cancer Institute Common Toxicity Criteria, version 4.0 (NCI-CTCAE) Grade ≥3 and the World Health Organization Mucositis Grading Scale (WHO) Grade ≥3 versus historical controls; secondary outcome measures included time to onset of severe OM following therapy initiation.At baseline, all patients included in final analysis (Compared to historical outcomes, PBMT aides in decreasing severe OM in patients with locally advanced HNSCC. PBMT represents a minimally invasive, prophylactic intervention to decrease OM as a major treatment-related side effect.

The new noninvasive finger sensor system NICCI (Getinge; Gothenburg, Sweden) allows continuous cardiac output monitoring. We aimed to investigate its cardiac output measurement performance.To investigate the NICCI system's cardiac output measurement performance.Prospective method comparison study.University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Fifty-one patients after cardiac surgery.We performed a method comparison study in 51 patients after cardiac surgery to compare NICCI cardiac output (CO NICCI ) and NICCI cardiac output calibrated to pulmonary artery thermodilution cardiac output measurement (CO NICCI-CAL ) with pulmonary artery thermodilution cardiac output (CO PAT ). As a secondary analysis we also compared CNAP cardiac output (CO CNAP ) and externally calibrated CNAP cardiac output (CO CNAP-CAL ) with CO PAT .We analysed 299 cardiac output measurement pairs. The mean of the differences (95% limits of agreement) between CO NICCI and CO PAT was 0.6 (-1.8 to 3.1) l min -1 with a percentage error of 48%. The mean of the differences between CO NICCI-CAL and CO PAT was -0.4 (-1.9 to 1.1) l min -1 with a percentage error of 29%. The mean of the differences between CO CNAP and CO PAT was 1.0 (-1.8 to 3.8) l min -1 with a percentage error of 53%. The mean of the differences between CO CNAP-CAL and CO PAT was -0.2 (-2.0 to 1.6) l min -1 with a percentage error of 35%.The agreement between CO NICCI and CO PAT is not clinically acceptable.The study was registered in the German Clinical Trial Register (DRKS00023189) after inclusion of the first patient on October 2, 2020.

Background Venous thromboembolism (VTE) is a serious complication, particularly in cancer patients undergoing free flap reconstruction. Subcutaneous enoxaparin is the conventional prophylaxis for VTE prevention, and serum anti-factor Xa (afXa) levels are being increasingly used to monitor enoxaparin activity. In this study, free flap patients receiving standard enoxaparin prophylaxis were prospectively followed to investigate postoperative afXa levels and 90-day VTE and bleeding-related complications. Methods Patients undergoing free tissue transfer during an 8-month period were identified and prospectively followed. Patients received standard fixed enoxaparin dosing at 30 mg twice daily in head and neck (H&N) and 40 mg daily in breast reconstructions. Target peak prophylactic afXa range was 0.2 to 0.5 IU/mL. The primary outcome was the occurrence of 90-day postoperative VTE- and bleeding-related events. Independent predictors of afXa level and VTE incidence were analyzed for patients that met the inclusion criteria. Results Seventy-eight patients were prospectively followed. Four (5.1%) were diagnosed with VTE, and six (7.7%) experienced bleeding-related complications. The mean afXa levels in both VTE patients and bleeding patients were subprophylactic (0.13 ± 0.09 and 0.11 ± 0.07 IU/mL, respectively). Forty-six patients (21 breast, 25 H&N) had valid postoperative peak steady-state afXa levels. Among these, 15 (33%) patients achieved the target prophylactic range: 5 (33%) H&N and 10 (67%) breast patients. The mean afXa level for H&N patients was significantly lower than for breast patients (p = 0.0021). Patient total body weight was the sole negative predictor of afXa level (R 2 = 0.47, p Conclusion Standard fixed enoxaparin dosing for postoperative VTE prophylaxis does not achieve target afXa levels for the majority of our free flap patients. H&N patients appear to be a particularly high-risk group that may require a more personalized and aggressive approach. Total body weight is the sole negative predictor of afXa level, supporting a role for weight-based enoxaparin dosing.

Research was carried out on the germination of seeds obtained from crossings between the cultivars of red raspberry (Rubus idaeus L.) ‘Sokolica’, ‘Willamette’, ‘Veten’, ‘Canby’ and ‘Glen Ample’ depending on the age of the seeds. The crossings were performed in the winter–spring of 2015–2018 in a heated greenhouse. The obtained seeds were stored dry in paper bags at a temperature of 4–5 °C. In January 2019, seeds were scarified and then cold stratified for 50 days and seeded in pots in a greenhouse. The seedling emergence was assessed 60 days after sowing. The seeds produced in 2015 had the lowest germination percentage (14% on average for all combinations of crosses), while the seeds produced in 2018 had a germination rate of 44.9%. Significant differences were also observed in the emergence of seedlings from different combinations. On average, the fewest seedlings were obtained from the combination ‘Glen Ample’ × ‘Willamette’ and the most from ‘Sokolica’ × ‘Willamette’.

The West Barracouta (BTW) field, one of the largest proven undeveloped gas fields off the south-eastern Australian coast, commenced production in April 2021. The project was developed by Esso-BHP Gippsland Basin Joint Venture (GBJV), a 50–50 JV between ExxonMobil’s subsidiary Esso Australia and BHP Petroleum. The BTW gas field is situated ~6 km south west of the existing Barracouta gas field and platform, the first GBJV platform in Bass Strait. The BTW development involved drilling two subsea production wells, installation of umbilical controls from the existing platform and installation of a ~6 km subsea flowline to connect to existing gas pipeline via a hot tap. The BTW team successfully navigated through engineering, fabrication, testing, mobilisation of an international team and installation of the facilities in a COVID environment. The paper shares insights on how to: manage fabrication impacts with closures and restricted workhours to minimise disruption to the project; complete videoconference Hazid Identification Risk Assessment workshops across different geographical locations; develop and execute methodology for distributed component integrated testing with hardware located in different geographical locations; complete remote inspections, Factory Acceptance Tests (FAT)/verification using videoconference; complete enhanced familiarisation and testing activities at shorebase, prior to offshore installation, given restrictions in overseas travel/access to FAT locations; and safely manage installation personnel to ensure continuity of activities in a COVID environment, e.g. platform, installation vessel and diver COVID requirements.

The West Barracouta (BTW), field one of the largest proven undeveloped gas fields off the south-eastern Australian coast, commenced production in April 2021. The project was developed by Esso-BHP Gippsland Basin Joint Venture (JV), a 50–50 JV between ExxonMobil’s subsidiary Esso Australia and BHP Petroleum. The BTW gas field is situated ~6 km south west of the existing Barracouta gas field and platform, the first Gippsland Basin Joint Venture platform in Bass Strait. The BTW development involved drilling two subsea production wells, installation of umbilical controls from the existing platform and installation of a ~6 km subsea flowline to connect to existing gas pipeline via a hot tap. The BTW team will share insights on how it: (1) utilised minimum kit solution and verification of existing asset condition; subsea hot tap into operational gas pipeline and re-use of existing platform J-tube to minimise works on and around the Barracouta Platform (including diving work). (2) Managed an Operator first – co-mingled wet gas subsea pipelines while operating in hydrate regions; via detailed water detection metre/software solution, downhole zone isolation and systematic operating guidelines. (3) Leveraged Installation Contractor competitive Front End Engineering and Design (FEED) enabling optimisation of facilities design/execution strategies to align with strengths and maximise overall project value. (4) Leveraged the OneSubsea/Subsea 7 Subsea Integration Alliance and global worldwide network to execute the subsea design (including qualification), manufacture and installation. (5) Utilised the incumbent Engineering, Procurement and Construction (EPC) contractor to integrate the subsea and topsides control systems to support a single operation system linked to the existing to Distributed Control System (DCS).

Positron emission tomography (PET) imaging in early Parkinson's disease (PD) subjects reveals that increased dopamine (DA) turnover and reduced dopamine transporter (DAT) density precede decreases in DA synthesis and storage. The rat α-synuclein preformed fibril (α-syn PFF) model provides a platform to investigate DA dynamics during multiple stages of α-syn inclusion-triggered nigrostriatal degeneration.We investigated multiple aspects of in vivo dopaminergic deficits longitudinally and similarities to human PD using translational PET imaging readouts.Longitudinal imaging was performed every 2 months in PFF and control rats for 7 months. [Early DA turnover increases and DAT binding decreases were observed in the ipsilateral striatum of PFF rats, progressing longitudinally. EDVR decreased 26%, 38%, and 47%, and BPThe relative preservation of DA synthesis and storage compared to robust progressive deficits in DAT density and increases in DA turnover in the rat α-syn PFF model display remarkable face validity to dopaminergic alterations in human PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Data on the efficacy of including definitive local therapy to the primary site for head and neck squamous cell carcinoma (HNSCC) patients with synchronous distant metastasis are lacking. In multiple different solid tumor types, there has been benefit when using systemic therapy followed by local consolidative therapy (stereotactic ablative radiotherapy or surgery) directed at metastases. We proposed to retrospectively evaluate patients at our institution that received definitive treatment to the primary.Single institution retrospective study evaluating 40 patients with metastatic HNSCC treated with definitive surgery (55%) or chemoradiation (45%) to the primary site from 2000 to 2020. The major endpoints were overall survival (OS) and progression-free survival (PFS) for the total population and multiple sub-groups. Some variables were evaluated with multiple covariates Cox model.The median PFS was 8.6 months (95% CI, 6.4-11.6), and OS was 14.2 months (95% CI, 10.9-27.5). In 28% of patients that received induction therapy, there was a twofold increase in median overall survival to 27.5 months. In the 33% of patients that received anti-PD-1 mAb as part of their treatment course, the median OS was significantly increased to 41.7 months (95% CI, 8.7-NR) versus 12.1 months (95% CI, 8.4-14.4) with a 5-year OS of 39%. Multivariate analysis for OS showed significance for age at diagnosis, use of IO, and number of metastatic sites.We observed impressive survival outcomes in metastatic HNSCC patients treated with definitive local therapy to the primary site in addition to induction and/or immunotherapy. Further study is warranted.Level of Evidence: 3.

Patient characteristics of control group

Comparison of clinical to pathologic stage migration between patients enrolled in 1 of 4 window trials compared to a second control group

Representativeness of study participants

Purpose:Neoadjuvant targeted therapy provides a brief, preoperative window of opportunity that can be exploited to individualize cancer care based on treatment response. We investigated whether response to neoadjuvant therapy during the preoperative window confers survival benefit in patients with operable head and neck squamous cell carcinoma (HNSCC).Patients and Methods:A pooled analysis of treatment-naïve patients with operable HNSCC enrolled in one of three clinical trials from 2009 to 2020 (NCT00779389, NCT01218048, NCT02473731). Neoadjuvant regimens consisted of EGFR inhibitors (n = 83) or anti-ErbB3 antibody therapy (n = 9) within 28 days of surgery. Clinical to pathologic stage migration was compared with disease-free survival (DFS) and overall survival (OS) while adjusting for confounding factors using multivariable Cox regression. Circulating tumor markers validated in other solid tumor models were analyzed.Results:92 of 118 patients were analyzed; all patients underwent surgery following neoadjuvant therapy. Clinical to pathologic downstaging was more frequent in patients undergoing neoadjuvant targeted therapy compared with control cohort (P = 0.048). Patients with pathologic downstage migration had the highest OS [89.5%; 95% confidence interval (CI), 75.7–100] compared with those with no stage change (58%; 95% CI, 46.2–69.8) or upstage (40%; 95% CI, 9.6–70.4; P = 0.003). Downstage migration remained a positive prognostic factor for OS (HR, 0.22; 95% CI, 0.05–0.90) while adjusting for measured confounders. Downstage migration correlated with decreased circulating tumor markers, SOX17 and TAC1 (P = 0.0078).Conclusions:Brief neoadjuvant therapy achieved pathologic downstaging in a subset of patients and was associated with significantly better DFS and OS as well as decreased circulating methylated SOX17 and TAC1.

CONSORT diagram of patients included neoadjuvant targeted therapy trials

Detection of methylated DNA in plasma of HNSCC patients

Comparison of clinical to pathologic stage migration between patients enrolled in 1 of 4 window trials compared to a control group

Purpose:Human papillomavirus (HPV) infection drives the development of some head and neck squamous cell carcinomas (HNSCC). This disease is rapidly increasing in incidence worldwide. Although these tumors are sensitive to treatment, approximately 10% of patients fail therapy. However, the mechanisms that underlie treatment failure remain unclear.Experimental Design:We performed RNA sequencing (RNA-seq) on tissues from matched primary- (pHNSCC) and metachronous-recurrent cancers (rHNSCC) to identify transcriptional differences to gain mechanistic insight into the evolutionary adaptations of metachronous-recurrent tumors. We used HPV-related HNSCC cells lines to investigate the effect of (i) NRF2 overexpression on growth in vitro and in vivo, (ii) oxidative phosphorylation (OXPHOS) inhibition using IACS-010759 on NRF2-dependent cells, and (iii) combination of cisplatin and OXPHOS inhibition.Results:The OXPHOS pathway is enriched in recurrent HPV-associated HNSCC and may contribute to treatment failure. NRF2-enriched HNSCC samples from The Cancer Genome Atlas (TCGA) with enrichment in OXPHOS, fatty-acid metabolism, Myc, Mtor, reactive oxygen species (ROS), and glycolytic signaling networks exhibited worse survival. HPV-positive HNSCC cells demonstrated sensitivity to the OXPHOS inhibitor, in a NRF2-dependent manner. Further, using murine xenograft models, we identified NRF2 as a driver of tumor growth. Mechanistically, NRF2 drives ROS and mitochondrial respiration, and NRF2 is a critical regulator of redox homeostasis that can be crippled by disruption of OXPHOS. NRF2 also mediated cisplatin sensitivity in endogenously overexpressing primary HPV-related HNSCC cells.Conclusions:These results unveil a paradigm-shifting translational target harnessing NRF2-mediated metabolic reprogramming in HPV-related HNSCC.

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Graphical Abstract

The aim of article is to present Mikołaj Zebrzydowski as an epistolographer. For this purpose there have been analyzed both his unpublished letters (housed in national libraries and archives) and the published ones. The examined correspondence comes from the years 1581–1615. The article discusses the themes covered explicitly and implicitly (deep meaning layer) in the letters, the relations with the addressees, the language and the style. The subjects of correspondence conducted by Mikołaj Zebrzydowski are strictly related to his public activity. So far, no letters of the voivode that were addressed to the members of the immediate family or were exclusively private in nature have been found. Most of the letters written by Zebrzydowski are concise, catious and focused on specifics, which seems to correspond to the secretive and pragmatic nature of the sender. There are already in the correspondence some traces of contesting the actions of Sigismund III before the Sandomierz sedition, which, of course, increase in the years 1606–1609. Letters addressed to a collective addressee deserve special attention. Unlike the ones intended for individual recipients, in the correspondence addressed to the wider public, the voivode expresses his feelings, often refers to authorities, tries to play with the emotions of readers, stylises his behavior and manipulates facts. To strengthen the power of expression he willingly uses amplification, one of the basic rhetorical devices. It should be considered that this type of correspondence was one of the most important propaganda tools used by the voivode., Celem niniejszego artykułu jest przybliżenie postaci Mikołaja Zebrzydowskiego jako epistolografa. Analizie poddano listy Zebrzydowskiego zarówno niepublikowane, znajdujące się w krajowych bibliotekach i archiwach, jak również wydane drukiem. Przebadana korespondencja pochodzi z lat 1581–1615. Omówiono problematykę poruszaną w listach (zarówno informacje przekazywane bezpośrednio, jak i te ukryte w „warstwie głębokiej” tekstu), relacje z adresatami listów, język oraz styl epistoł. Tematyka korespondencji prowadzonej przez Mikołaja Zebrzydowskiego jest ściśle powiązana z jego publiczną działalnością. Jak dotąd nie udało odnaleźć się listów wojewody, które były kierowane do członków najbliższej rodziny bądź miały wyłącznie prywatny charakter. Większość listów napisanych przez Zebrzydowskiego cechuje oględność, skupienie się na konkrecie i brak rozwlekłości, co zdaje się korespondować ze skrytą i pragmatyczną naturą nadawcy. Już w korespondencji przedrokoszowej odnaleźć można ślady kontestacji poczynań Zygmunta III, które - rzecz jasna - przybrały na sile w latach 1606–1609. Na szczególną uwagę zasługują listy kierowane do zbiorowego adresata. W odróżnieniu od epistoł przeznaczonych do pojedynczych odbiorców, w korespondencji zwróconej do szerszej publiki wojewoda wspomina o swoich uczuciach, często odwołuje się do autorytetów, stara się poruszyć emocje czytelników, stylizuje swoje zachowanie, manipuluje faktami. By wzmocnić siłę wypowiedzi, chętnie korzysta z amplifikacji, jednego z podstawowych narzędzi w retoryce. Uznać należy, że ten typ korespondencji był jednym z ważniejszych narzędzi propagandowych stosowanych przez wojewodę.

The interest in NK cells and their cytotoxic activity against tumour, infected or transformed cells continuously increases as they become a new efficient and off-the-shelf agents in immunotherapies. Their actions are balanced by a wide set of activating and inhibitory receptors, recognizing their complementary ligands on target cells. One of the most studied receptors is the activating CD94/NKG2C molecule, which is a member of the C-type lectin-like family. This review is intended to summarise latest research findings on the clinical relevance of NKG2C receptor and to examine its contribution to current and potential therapeutic strategies. It outlines functional characteristics and molecular features of CD94/NKG2C, its interactions with HLA-E molecule and presented antigens, pointing out a key role of this receptor in immunosurveillance, especially in the human cytomegalovirus infection. Additionally, the authors attempt to shed some light on receptor’s unique interaction with its ligand which is shared with another receptor (CD94/NKG2A) with rather opposite properties.