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Abstract The COVID-19 pandemic has had a profound impact on almost all aspects of society. Cultural heritage sites, which are deeply intertwined with the tourism industry, are no exception. The direct impacts of the virus on the population, as well as indirect impacts, such as government-mandated measures including social distancing, face coverings, and frequent temporary closures of sites, have greatly impacted visitor experiences at heritage sites. To quantitatively evaluate the impact of these measures from the perspective of visitors, we collected 1.4 millions visitor reviews from the Google Maps platform for 775 heritage sites. We analyzed visiting rates using the number of online reviews as a proxy and adopt state-of-the-art natural language processing techniques to more deeply understand visitor perception of preventive measures put in place to control the spread of COVID-19. Our findings reveal that even if visitor focus on COVID-19 has significantly decreased, there may still be notable difference between actual and expected number of reviews, suggesting that visitor involvement (e.g., number of visitors) for cultural heritage sites, especially urban indoor sites, needs more time to recover. Our findings further show that most comments by visitors to sites were associated with negative sentiment toward restricted access, but recognized the necessity of other safeguarding measures (e.g., social distancing and the requirement for face coverings). Moreover, they exhibited negative sentiment towards staff or other visitors who did not adhere to these measures. We make specific recommendations for heritage sites to adapt to the COVID-19 pandemic and a more general observation that the method used to gather information from online reviews in this paper will be effective in measuring visitor perceptions towards specific aspects of heritage sites, particularly in capturing changes in perception before and after unexpected or disruptive events at heritage sites.

Nuclear growth differentiation factor 15 (GDF15) reduces the binding of the mothers' against decapentaplegic homolog (SMAD) complex to its DNA-binding elements. However, the stimuli that control this process are unknown. Here, we examined whether saturated fatty acids (FA), particularly palmitate, regulate nuclear GDF15 levels and the activation of the SMAD3 pathway in human skeletal myotubes and mouse skeletal muscle, where most insulin-stimulated glucose use occurs in the whole organism. Human LHCN-M2 myotubes and skeletal muscle from wild-type and Gdf15−/− mice fed a standard (STD) or a high-fat (HFD) diet were subjected to a series of studies to investigate the involvement of lipids in nuclear GDF15 levels and the activation of the SMAD3 pathway. The saturated FA palmitate, but not the monounsaturated FA oleate, increased the expression of GDF15 in human myotubes and, unexpectedly, decreased its nuclear levels. This reduction was prevented by the nuclear export inhibitor leptomycin B. The decrease in nuclear GDF15 levels caused by palmitate was accompanied by increases in SMAD3 protein levels and in the expression of its target gene SERPINE1, which encodes plasminogen activator inhibitor 1 (PAI-1). HFD-fed Gdf15−/− mice displayed aggravated glucose intolerance compared to HFD-fed WT mice, with increased levels of SMAD3 and PAI-1 in the skeletal muscle. The increased PAI-1 levels in the skeletal muscle of HFD-fed Gdf15−/− mice were accompanied by a reduction in one of its targets, hepatocyte growth factor (HGF)α, a cytokine involved in glucose metabolism. Interestingly, PAI-1 acts as a ligand of signal transducer and activator of transcription 3 (STAT3) and the phosphorylation of this transcription factor was exacerbated in HFD-fed Gdf15−/− mice compared to HFD-fed WT mice. At the same time, the protein levels of insulin receptor substrate 1 (IRS-1) were reduced. These findings uncover a potential novel mechanism through which palmitate induces the SMAD3-PAI-1 pathway to promote insulin resistance in skeletal muscle by reducing nuclear GDF15 levels. [ABSTRACT FROM AUTHOR]

The first Neolithic farmers arrived in the Western Mediterranean area from the East. They established settlements in coastal areas and over time migrated to new environments, adapting to changing ecological and climatic conditions. While farming practices and settlements in the Western Mediterranean differ greatly from those known in the Eastern Mediterranean and central Europe, the extent to which these differences are connected to the local environment and climate is unclear. Here, we tackle this question by compiling data and proxies at a superregional and multi-scale level, including archaeobotanical information, radiocarbon dates and paleoclimatic models, then applying a machine learning approach to investigate the impact of ecological and climatic constraints on the first Neolithic humans and crops. This approach facilitates calculating the pace of spread of farming in the Western Mediterranean area, modelling and estimating the potential areas suitable for settlement location, and discriminating distinct types of crop cultivation under changing climatic conditions that characterized the period 5900 – 2300 cal. BC. The results of this study shed light onto the past climate variability and its influence on human distribution in the Western Mediterranean area, but also discriminate sensitive parameters for successful agricultural practices. Neolithic farming practices differed across the Mediterranean. Here, the authors apply a machine learning approach to combined archaeological and paleoclimatic data, investigating the impact of climate on the spread of agriculture in the Mediterranean. [ABSTRACT FROM AUTHOR]

Background: Complete mesocolon excision (CME) and D3-lymphadenectomy concepts have gained popularity for the surgical treatment of right colon cancer in comparison to the conventional laparoscopic right hemicolectomy (CLRH). The rationale of CME is to dissect the embryological planes between the mesenteric plane and the parietal fascia to remove the mesentery within a complete envelope of mesenteric fascia and visceral peritoneum that contains lymph nodes, the central vascular ligation, and adequate bowel length to remove involved pericolic lymph nodes in the longitudinal direction, having as the main goal to improve the oncological results. CME with D3-lymphadenectomy is challenge since involves the excision of the lymph adipose tissue covering the medial edge of the superior mesenteric vein (SMV) (trunk of Gillot, TG), and the gastrocolic trunk of Henle (GTH). We describe a LRH with CME using a cranial approach allowing an easier central vessels origin identification. Technique: Through the supramesocolic approach, gastrocolic ligament is opened and the GTH and the middle colic artery (MCA) and vein (MCV) origins are identified. Hepatic flexure is mobilized, and a gauze is placed above the mesenteric vessels. Then, the SMV is identified, dividing the ileocolic vessels origin. The plane between the Gerota and Toldt fascias is opened, identifying duodenum, pancreas, and the gauze previously placed. Following this plane and the SMV along the TG, the GTH and its branches are identified. The superior right colic vein, and the MCA and MCV right branches are divided. After that, colon is fully mobilized laterally opening the parietocolic gutter and an intracorporeal anastomosis is performed. Conclusion: CME could lead to an improvement of oncological results due to a wider mesocolic excision in comparison to conventional D2-lymphadenectomy. Cranial approach facilitates the vessels origin identification to perform a true central ligation. [ABSTRACT FROM AUTHOR]

There is growing evidence about how physical activity can improve cancer care. Unfortunately, exercise is still not widely prescribed to oncology patients, despite the benefit it brings. For this to occur, it is necessary for a multidisciplinary approach involving different types of healthcare professionals, given that each treatment be tailored for each single case. Besides incorporating appropriate infrastructures and referral pathways, we need to integrate exercise into healthcare practice, which ameliorates patients' quality of life and treatment side effects. From the Spanish Society of Medical Oncology (SEOM), and through the Exercise and Cancer Working Group, we indicate considerations, analyze patient care scenarios, and propose a referral pathway algorithm for exercise prescription, taking in account the patient's needs. In later sections of this paper, we describe how this algorithm could be implemented, and how the exercise programs should be built, including the physical activity contents, the settings, and the delivery mode. We conclude that professionals, infrastructures, and organizations should be available at every assistance level to create programs providing adequate exercise training for cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies have established the safety and efficacy of Superparamagnetic Iron Oxide (SPIO, Magtrace®) for delayed sentinel lymph node biopsy (SLNB) in patients with ductal carcinoma in situ (DCIS) who are undergoing mastectomy. The aim of our study was to measure cost containment with use of Magtrace® in comparison to upfront SLNB with traditional technetium-99 lymphatic tracer. Methods: A total of 41 patients at our institution underwent mastectomy with Magtrace® injection for DCIS and were included in our single-institution, retrospective analysis. For comparison, total charges data were obtained for an upfront SLNB at the time of mastectomy. Cost comparison analysis was then performed against charges for intraoperative Magtrace® injection with additional charges incorporated for those patients who required return to the operating room for delayed SLNB. Total cost containment for the cohort with use of Magtrace® was then measured. Results: Of the 41 patients who underwent Magtrace® injection, two patients required return to the operating room for a delayed SLNB for invasive disease. Including these charges for a second encounter into our cost analysis, the use of Magtrace® still yielded an overall cost containment of $205,793.55 in our cohort when comparing to patients who underwent upfront SLNB. For patients who underwent Magtrace® injection and did not require return to the operating room, charges were reduced by $6,768.52 per patient. Conclusion: The use of Magtrace® for delayed SLNB in patients with DCIS undergoing mastectomy yielded a significant overall cost containment, further supporting its use in this patient population. [ABSTRACT FROM AUTHOR]

Ageing-related changes in the vascular wall influence the function of different organs; for this reason, we assessed how arterial stiffness measured by carotid-femoral pulse wave velocity (cf-PWV) modulates: the basal cognitive performance and the change in cognitive performance over the follow-up time. We developed a prospective, population-based cohort study with 1581 participants aged > 65 years were obtained from the Toledo Study for Healthy Aging. Participants from the second wave (2011–2013) were selected for the cross-sectional analysis. Those who also performed the cognitive assessment in the third wave (2015–2017) were selected for the prospective analysis. Arterial stiffness was evaluated by cf-PWV. Multivariate segmented regression models were used to evaluate the association between cf-PWV scores and basal neuropsychological evaluation scores and change of neuropsychological evaluation scores along follow-up. Cross-sectional analysis showed that as cf-PWV grew within the cf-PWV (5– < 10) category an improvement was observed in 7-min test, free short-term memory, and hole peg test. Furthermore, in the cf-PWV (> 13–18) category a decrease was observed in total short-term memory, free long-term memory, and total long-term memory. Prospective analysis showed a progressive worsening of cognitive function as cf-PWV increases within the cf-PWV (> 13–18) category in 7-min test, object denomination, immediate and short-term memory, and hole peg test, while in the cf-PWV (5– < 10) category, there was observed a decrease in Cumulative Executive Dysfunction Index score and short-term memory. In conclusion, a higher cf-PWV score is associated with worse cognitive performance, and with a worse evolution, reinforcing the need to plan interventions to delay arterial stiffness and its consequences. [ABSTRACT FROM AUTHOR]

European badgers (Meles meles) play an important role in the epidemiology of bovine tuberculosis (caused by Mycobacterium bovis) in England, but little is known about the prevalence of atypical mycobacteriosis. Badgers are also known to be infected by other infectious agents, and the relationship between mycobacteriosis and concomitant infections needs further investigation. Overall, 88 badger carcasses from the Midlands of England collected between July 2016-August 2017 were selected for histopathological examination based on the degree of autolysis (mild), mycobacterial culture results and a balanced sex ratio. Mycobacteria were cultured from 44 badgers, of which 31 were mycobacteria belonging to the M. tuberculosis complex (MTBC) (based on IS6110 PCR and Hsp64 and/or rRNA PCR and sequencing) and 13 were non-tuberculous atypical mycobacteria (NTM). Mycobacteria were not cultured from the remaining 44 animals. Histologically, the most common findings were silica-laden macrophages (85%), granulomas (53%), sarcocystosis (47%), nephritis (31%), portal/periportal hepatitis (26%), ulcerative dermatitis (18%). Culturable mycobacteriosis was associated with higher prevalence of granulomas (p < 0.001) and lower prevalence of hepatitis (p = 0.003). NTM (M. nonchromogenicum, M. avium complex, M. hassiacum, M. malmoense, M. vaccae.) infections were associated with granulomatous pneumonia, and M. malmoense was associated with pyogranulomatous and ulcerative dermatitis. In conclusion, this study describes, for the first time, histological lesions associated with NTM in badgers, the histomorphology of which was similar to those caused by MTBC. In addition, the negative relationship between mycobacteriosis and periportal hepatitis may indicate a complex relationship between mycobacteriosis and other diseases, as previously observed with tuberculosis. [ABSTRACT FROM AUTHOR]

Animated films are highly popular in society, particularly among children and adolescents. During film production, selecting an adequate colour palette and scene dynamism is crucial for creating a visual impact on the audience. However, the influence of visual aesthetics, such as colour and scene dynamism on visual fatigue remains unexplored. In the present study, visual fatigue was assessed and compared in 30 young participants after viewing two popular films: Spider-Man: Across the Spider-Verse, an active, fast-paced film, and My Neighbour Totoro, a more relaxed film. Both films were viewed twice, once with the original colour palette and once in greyscale. Watching Spider-Man film induced a greater degree of visual fatigue than My Neighbour Totoro in two subjective questionnaires evaluating visual fatigue, and in the vergence facility and binocular accommodative facility tests. Moreover, important differences in the visual dynamics and colour aspects between both films were found. These results demonstrate that the high-paced and high-colour aspects of films directly affect visual fatigue. Future animated film producers should consider these factors that are relevant to their audiences. [ABSTRACT FROM AUTHOR]

Abstract The data and debates around the negative impact of online work for women’s work-life balance during the digital acceleration generated by the COVID-19 crisis have lent greater relevance to the study of gender and the digital economy. This paper sheds light on this complex relationship by systematically studying the research on gender in the digital economy over the last 25 years. The methodology used is a systematic literature review (SLR) of scientific works and policy papers across different social sciences from 1995 to 2020 in the Google Scholars and Scopus databases. The SLR has resulted in the creation of three samples on which a quantitative and qualitative analysis was carried out to evaluate the volume of the research, trends across time, gender approaches and study topics. The general conclusions indicate that gender approaches to the digital economy stem from a wide range of academic disciplines, and also that there is a lack of theoretical consistency about gender analysis. First, the paper provides an overview of the volume of works and an analysis of some trends across time. Second, it identifies the three main gender approaches applied to the digital economy: (1) the ‘feminist theory of technology and ICT’ approach; (2) the ‘feminist political economy’ approach; (3) the ‘mainstream economic analysis and women’s participation and labour in the digital economy’ approach. Moreover, it distinguishes eight main gender analysis issues within these three approaches. Finally, the paper concludes by identifying future developments for a feminist political economy framework for the digital economy.

Amyotrophic lateral sclerosis (ALS) is characterised primarily by motor system degeneration, with clinical evidence of cognitive and behavioural change in up to 50% of cases. We have shown previously that resting-state EEG captures dysfunction in motor and cognitive networks in ALS. However, the longitudinal development of these dysfunctional patterns, especially in networks linked with cognitive-behavioural functions, remains unclear. Longitudinal studies on non-motor changes in ALS are essential to further develop our understanding of disease progression, improve care and enhance the evaluation of new treatments. To address this gap, we examined 124 ALS individuals with 128-channel resting-state EEG recordings, categorised by cognitive impairment (ALSci, n = 25), behavioural impairment (ALSbi, n = 58), or non-impaired (ALSncbi, n = 53), with 12 participants meeting the criteria for both ALSci and ALSbi. Using linear mixed-effects models, we characterised the general and phenotype-specific longitudinal changes in brain network, and their association with cognitive performance, behaviour changes, fine motor symptoms, and survival. Our findings revealed a significant decline in -band spectral power over time in the temporal region along with increased -band power in the fronto-temporal region in the ALS group. ALSncbi participants showed widespread β-band synchrony decrease, while ALSci participants exhibited increased co-modulation correlated with verbal fluency decline. Longitudinal network-level changes were specific of ALS subgroups and correlated with motor, cognitive, and behavioural decline, as well as with survival. Spectral EEG measures can longitudinally track abnormal network patterns, serving as a candidate stratification tool for clinical trials and personalised treatments in ALS. [ABSTRACT FROM AUTHOR]

This study explores the role of family interpersonal relationships in coping with the effects of COVID-19 and examines factors that place Latinx adolescents at risk for adverse effects of COVID-19 and promote resilience. We used a qualitative inquiry to explore the impact of COVID-19 on Latinx New York City adolescents, using sensitizing concepts from the family stress and coping theory as a data organization and analysis strategy. Five focus groups with 26 students aged 13 to 17 years old were conducted, and emergent themes were identified from the data. Latinx student participants reported disruptions in their family structure and interaction patterns. Families of these adolescents faced income loss, death, and illness from COVID-19, which impacted parent-child relationships. The absence of needed community resources undermined family resilience. Yet, students used internal resources found in their families and within themselves to cope with the COVID-19 stressors. Participants reported challenges within the family, school, and youth's daily experiences. To lessen the pandemic's impact on Latinx students in the midst of the ever-changing COVID-19 pandemic requires an ecological approach in which family, school, community, and policy factors are considered, and partnerships at each of these levels are established. Efforts to enhance family-school collaboration, equitable access to mental health services, youth outreach, and strengthen existing internal and external resources in the lives of Latinx students are key to promoting their well-being. [ABSTRACT FROM AUTHOR]

Objective: Many stroke survivors still present with upper-limb paresis six months post-stroke, impacting their autonomy and quality of life (QoL). We designed an enriched Music-supported Therapy (eMST) program to reduce disability in this population. We evaluated the eMST's effectiveness in improving functional abilities and QoL in chronic stroke individuals compared to the conventional motor program Graded Repetitive Arm Supplementary Program (GRASP). Methods: We conducted a pragmatic two-arm parallel-group randomized controlled trial with a 3-month follow-up and masked assessment. The eMST involved playing instruments during individual self-administered and group music therapy sessions. The GRASP consisted of self-administered motor exercises using daily objects. Both interventions were completed at home with telemonitoring and involved four one-hour weekly sessions for 10 weeks. The primary outcome was upper-limb motor function measured with the Action Research Arm Test. Secondary outcomes included motor impairment, daily life motor performance, cognitive functions, emotional well-being, QoL, self-regulation, and self-efficacy. Intention-to-treat (ITT) and per-protocol (PP) analyses were conducted including participants who discontinued the intervention and those who completed it entirely, respectively. Results: Fifty-eight chronic stroke patients were randomized to the eMST-group (n = 26; age: 64.2 ± 12.5; 6 [23.1%] females; 2.8 ± 2.9 years post-stroke), and the control group (n = 32; age: 62.2 ± 12; 8 [25%] females; 1.8 ± 6.2 years post-stroke). The eMST-group had more participants achieving a clinically relevant improvement in motor impairment post-intervention than the control group for the ITT (55% vs 21.6%; OR = 4.5 (95% CI 1.4–14); p =.019) and PP analyses (60% vs 20%; OR = 6 (95% CI 1.5–24.7); p =.024), sustained at follow-up. The eMST-group reported greater improvements in emotion (difference = 11.1 (95% CI 0.8–21.5; p = 0.36) and participation (difference = 10.3 (95% CI 0.6–25.9); p = 0.41) subscales of QoL, and higher enjoyment during the sessions (difference = 1 (95% CI 0.3–1.5); p = 0.12). No changes were found in other outcomes. Conclusion: eMST demonstrated superiority over conventional motor rehabilitation program in enhancing upper-limb functions and QoL in chronic stroke individuals. Trial Registration: ClinicalTrials.gov (ID: NCT04507542). [ABSTRACT FROM AUTHOR]

When considering the possibility of storing information in the sequence of monomer residues within an AB-type copolymer chain, it is constructive to model that sequence as a string of ones and zeros. The intramolecular environment around any given digit (say a "1") can then be represented by another string of integers—a code—obtained by summing pairs of digits at equivalent positions, in both directions, from that digit. The code can include only integers 0, 1 and 2, and can represent a number in any base b higher than 2. In base b = 3 the resulting set of codes includes all numbers (because only digits 0, 1 and 2 occur in ternary expansions), but in any base b > 3 the codes define a limited set of numbers comprising a fractal we term a Smith–Cantor set. The 1H NMR spectrum of a random, AB-type co(polyester-imide) shows, on complexation with pyrene, a pattern of complexation shifts approximating very closely to the Smith–Cantor set for which b = 4. Other co(polyimide) complexes show a 1H NMR pattern corresponding to a specific sub-set of this fractal. The sub-set arises from a "stop-at-zero" limitation, whereby digits in the initial string are set to zero for code-generating purposes if they occur beyond a zero, as viewed from the central "1". The limitation arises in copolymers where pyrene binds by intercalation between pairs of adjacent diimide residues. This numerical approach provides a complete, unifying theory to account for the emergence of fractal character in the 1H NMR spectra of AB-type copolymer complexes. [ABSTRACT FROM AUTHOR]

Recently, CNN-based all-in-one image enhancement methods have been proposed to solve multiple image degradation tasks. However, these CNN-based methods usually have two limitations. One limitation is that they usually design a specific encoder for each image enhancement task, lacking of a unified and simple framework. The other limitation is that they can not effectively capture global image degradation information, as use of the CNN-based encoders has a limited local receptive field. In this work, we propose a TransEncoder-based All-in-one Image Enhancement Network (TAENet), with a single encoder and a decoder, for simultaneously handling multiple image enhancement tasks. Specifically, we propose a Transformer-based Encoder (TransEncoder), which introduces instance normalization to transformer for color recovery. The TransEncoder model global degradation information by using the transformer's global self-attention mechanism. Additionally, inspired by the Mie scattering model, we propose a novel depth loss function for perceiving image depth information by minimizing the depth difference between the enhanced image and the ground-truth, thus further improving model performance. Moreover, a novel contrastive loss is introduced to strengthen task-generalization performance by enhancing the model's representation capability. Experiments show that the TAENet outperforms 24 state-of-the-art methods on image dehazing, image deraining, and low-light image enhancement. [ABSTRACT FROM AUTHOR]

We established confrontations between two different fungi, i.e., the maize anthracnose and stalk rot pathogen Colletotrichum graminicola, and the ubiquitous fungus Aspergillus nidulans, and different biocontrol species, i.e., Bacillus subtilis, Bacillus velezensis, and Bacillus amyloliquefaciens. In all fungus–bacterium confrontations tested, growth arrest and, thus, distance inhibition was observed on solid substrata. LC–MS/MS analyses of culture filtrates suggested formation of several metabolites only synthesized in confrontations. Interestingly, microscopy of fungal hyphae grown in liquid medium showed protrusions and color changes occurred only in media harboring fungus-bacterium confrontations. These observations indicate metabolic re-programming and suggest formation of putative secondary metabolites in interactions involving microbial biocontrol agents. [ABSTRACT FROM AUTHOR]

Key message: Inventory and seasonal variation of terpene emissions from tropical trees in French Guiana: implications for environmental and ecological roles. A limited understanding of foliar terpene emissions from different tree species is prominent in diverse tropical forests. We conducted a study in French Guiana, screening BVOC emissions from 36 tropical woody species. We focused on 32 species in the dry season and 33 in the wet season, documenting terpene emissions for the first time in some of these tree species. Our findings show that 93.8% emitted terpenes in the dry season, while only 33.3% did so in the wet season. Terpene emissions ranged from 0.01 to 80.9 μg g−1 h−1 in the dry season and 0 to 11.7 μg g−1 h−1 in the wet season, consistent with previous reports. We identified and quantified 23 terpene compounds, including 19 monoterpenes and 4 sesquiterpenes. Additionally, 2 non-terpenoid compounds were detected: 2,2,4,6,6-pentamethylheptane (with no detected emissions in the dry season) and toluene. Among the monoterpenes, the most abundant were α-terpinolene, limonene, α-pinene, β-ocimene, and sabinene. As for sesquiterpenes, β-caryophyllene, α-caryophyllene, and α-copaene were observed during the dry season, while during the wet season, α-terpinolene predominated, followed by limonene, α-pinene, sabinene, β-caryophyllene, and α-copaene. Isoprene was detected in most of the species studied in both seasons. Sesquiterpene emissions displayed a notable phylogenetic pattern, whereas total terpenes and monoterpenes did not; however, total terpenes and monoterpenes exhibited a significant seasonal influence. Our study demonstrates that seasonality strongly influences BVOC production in tropical trees, with higher emissions in the dry season. These findings imply that various factors and conditions influence tree emissions in this tropical forest, affecting their ecological, environmental, and climatic roles, as well as the implementation of atmospheric chemistry models. [ABSTRACT FROM AUTHOR]

Health-related quality of life (HRQoL) data are important indicators of health status in patients with lymphoma. The objective of this analysis was to assess the impact of treatment with Sandoz rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on HRQoL in treatment-naïve adult patients with diffuse large B-cell lymphoma (DLBCL) included in the prospective, real-world REFLECT study. REFLECT is the first prospective study to assess HRQoL in patients with DLBCL treated with a rituximab biosimilar. HRQoL was assessed via the patient-reported European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire at baseline, mid-treatment (month 3), end of treatment (month 6), and follow-up (months 9 and 12). Subgroup analyses were performed to evaluate the influence of baseline characteristics on HRQoL, and associations between baseline HRQoL and treatment response. HRQoL was assessed in 169 patients. Mean global health status score remained stable from baseline (54.8) to mid-treatment (month 3; 54.7), before steadily improving through to end of treatment (month 6; 61.4), and follow-up month 9 (64.9) and month 12 (68.8). Similar trends were observed across most functional and symptom subscales. Higher cognitive, physical, or role functioning, and less appetite loss, diarrhea, fatigue, or pain at baseline, were all associated with an improved likelihood of reaching a complete versus partial response at the end of treatment. Overall, these findings confirm the HRQoL benefits of R-CHOP therapy in treatment-naïve adult patients with DLBCL, and suggest that baseline HRQoL may be predictive of treatment response. [ABSTRACT FROM AUTHOR]

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Background: To investigate the reproducibility of automated volumetric bone mineral density (vBMD) measurements from routine thoracoabdominal computed tomography (CT) assessed with segmentations by a convolutional neural network and automated correction of contrast phases, on diverse scanners, with scanner-specific asynchronous or scanner-agnostic calibrations. Methods: We obtained 679 observations from 278 CT scans in 121 patients (77 males, 63.6%) studied from 04/2019 to 06/2020. Observations consisted of two vBMD measurements from Δdifferent reconstruction kernels (n = 169), Δcontrast phases (n = 133), scan Δsessions (n = 123), Δscanners (n = 63), or Δall of the aforementioned (n = 20), and observations lacking scanner-specific calibration (n = 171). Precision was assessed using root-mean-square error (RMSE) and root-mean-square coefficient of variation (RMSCV). Cross-measurement agreement was assessed using Bland-Altman plots; outliers within 95% confidence interval of the limits of agreement were reviewed. Results: Repeated measurements from Δdifferent reconstruction kernels were highly precise (RMSE 3.0 mg/cm3; RMSCV 1.3%), even for consecutive scans with different Δcontrast phases (RMSCV 2.9%). Measurements from different Δscan sessions or Δscanners showed decreased precision (RMSCV 4.7% and 4.9%, respectively). Plot-review identified 12 outliers from different scan Δsessions, with signs of hydropic decompensation. Observations with Δall differences showed decreased precision compared to those lacking scanner-specific calibration (RMSCV 5.9 and 3.7, respectively). Conclusion: Automatic vBMD assessment from routine CT is precise across varying setups, when calibrated appropriately. Low precision was found in patients with signs of new or worsening hydropic decompensation, what should be considered an exclusion criterion for both opportunistic and dedicated quantitative CT. Relevance statement: Automated CT-based vBMD measurements are precise in various scenarios, including cross-session and cross-scanner settings, and may therefore facilitate opportunistic screening for osteoporosis and surveillance of BMD in patients undergoing routine clinical CT scans. Key Points: Artificial intelligence-based tools facilitate BMD measurements in routine clinical CT datasets. Automated BMD measurements are highly reproducible in various settings. Reliable, automated opportunistic osteoporosis diagnostics allow for large-scale application. [ABSTRACT FROM AUTHOR]

Abstract In Alzheimer’s disease (AD), tau phosphorylation in the brain and its subsequent release into cerebrospinal fluid (CSF) and blood is a dynamic process that changes during disease evolution. The main aim of our study was to characterize the pattern of changes in phosphorylated tau (p‐tau) in the preclinical stage of the Alzheimer’s continuum. We measured three novel CSF p‐tau biomarkers, phosphorylated at threonine‐181 and threonine‐217 with an N‐terminal partner antibody and at threonine‐231 with a mid‐region partner antibody. These were compared with an automated mid‐region p‐tau181 assay (Elecsys) as the gold standard p‐tau measure. We demonstrate that these novel p‐tau biomarkers increase more prominently in preclinical Alzheimer, when only subtle changes of amyloid‐β (Aβ) pathology are detected, and can accurately differentiate Aβ‐positive from Aβ‐negative cognitively unimpaired individuals. Moreover, we show that the novel plasma N‐terminal p‐tau181 biomarker is mildly but significantly increased in the preclinical stage. Our results support the idea that early changes in neuronal tau metabolism in preclinical Alzheimer, likely in response to Aβ exposure, can be detected with these novel p‐tau assays.

Introduction: Drug regulatory agencies are particularly interested in pharmacovigilance data relating to medication errors (MEs) involving a product-related cause (problems with drug names, packaging, labels, tablet marking, modalities of drug use, or instructions for users), an educational failure, or a 'never event'. Older adults are particularly affected by MEs but little is known about the root causes of MEs, which could be a focus for regulatory agencies. Objective: The aim of this study was to describe and characterise MEs associated or not associated with adverse reactions that have occurred in older adults and fall under the scope of drug regulatory agencies. Method: A retrospective and descriptive analysis of pharmacovigilance data from the French Pharmacovigilance Network was performed. All ME reports, with or without adverse effects (AEs), which occurred from 1 September 2019 to 31 August 2020 and involved adults aged 75 years and over were analysed. We conducted a globally descriptive analysis of MEs, in particular on root causes in the scope of drug regulatory agencies (i.e. product-related cause, educational failure, 'never events'). Results: During the study period, 802 MEs were reported to the French pharmacovigilance system; 305 (38.0%) were associated with AEs (of which 171 [56.1%] were serious and 13 [4.3%] were fatal). The mean age of patients was 85.2 years and 493 (61.5%) were females. Globally, 224 (27.9%) of MEs had at least one root cause in the scope of the regulatory agencies and were more frequently observed in cases of MEs with AEs compared with those without (174 [57.1%] vs. 46 [9.2%]). The first root cause was an educational problem (159, 71%), followed by 'never events' (94, 42%) and product-related causes (20, 9%). MEs due to problems in the scope of regulatory agencies occurred more frequently at the administration and prescription stages and consisted of a wrong drug, wrong dose, and dosage/concentration. Conclusions: In the older population, the proportion of MEs for which a drug regulatory agency could act is high, confirming the importance of reporting MEs to pharmacovigilance in order to implement risk reduction measures. The ignorance of medication use was the first reason for errors, and actions taken by the health authorities should focus on producing visible and understandable instructions for healthcare professionals and patients. It is also necessary to collaborate closely with the manufacturers to improve packaging, labelling and product nomenclature to completely safeguard the use of their products. [ABSTRACT FROM AUTHOR]

Human activities that define the Anthropocene can lead to multi-faceted (social, ecological, economic) problems, such as biological invasions. Yet, interdisciplinary collaborations focused on understanding their causes and finding solutions remain relatively scarce. Telecoupling lens helps to conceptualize the biological invasions process (transport–introduction–establishment–invasion) across distal coupled human–nature systems. Using invasive non-native plants as an example, we explain how their invasion can alter either one or both of the sending (native) and receiving (invaded) systems. This occurs through multi-directional flows (e.g., species, knowledge), mediated by numerous dynamic agents (e.g., policymakers, immigrants, gardeners, scientists) that act at different temporal and geographic scales. Importantly, adopting the telecoupling perspective, we can incorporate policy and management into the invasion process by defining information flows and institutions as influential factors of the invasion process. Despite its substantial potential to improve our understanding of invasive species, the integration of the telecoupling perspective with traditional invasion frameworks remains largely unexplored. [ABSTRACT FROM AUTHOR]

Purpose: To assess the value of radiation therapy (RT) with helical tomotherapy (HT) in the management of locally advanced malignant pleural mesothelioma (MPM) receiving no or lung-sparing surgery. Methods: Consecutive MPM cases not undergoing extrapleural pneumonectomy and receiving intensity-modulated (IM) HT were retrospectively evaluated for local control, distant control, progression-free survival (PFS), and overall survival (OS). Impact of age, systemic treatment, RT dose, and recurrence patterns was analyzed by univariate and multivariate analysis. As a secondary endpoint, reported toxicity was assessed. Results: A total of 34 localized MPM cases undergoing IMHT were identified, of which follow-up data were available for 31 patients. Grade 3 side effects were experienced by 26.7% of patients and there were no grade 4 or 5 events observed. Median PFS was 19 months. Median OS was 20 months and the rates for 1‑ and 2‑year OS were 86.2 and 41.4%, respectively. OS was significantly superior for patients receiving adjuvant chemotherapy (p = 0.008). Conclusion: IMHT of locally advanced MPM after lung-sparing surgery is safe and feasible, resulting in satisfactory local control and survival. Adjuvant chemotherapy significantly improves OS. Randomized clinical trials incorporating modern RT techniques as a component of trimodal treatment are warranted to establish an evidence-based standard of care pattern for locally advanced MPM. [ABSTRACT FROM AUTHOR]

Background: Continued dietary treatment since early diagnosis through newborn screening programs usually prevents brain-related complications in phenylketonuria (PKU). However, subtle neurocognitive and brain alterations may be observed in some adult patients despite early treatment. Nevertheless, neuropsychological and neuroimaging studies in the field remain scarce. Objectives: This work aimed to determine possible neuropsychological and structural brain alterations in treated adult patients with PKU. Methods: Thirty-five patients with PKU and 22 healthy controls (HC) underwent neuropsychological assessment and T1-weighted magnetic resonance imaging on a 3 T scanner. FreeSurfer (v.7.1) was used to obtain volumetric measures and SPSS (v27.0.1.0) was used to analyze sociodemographic, neuropsychological, volumetric, and clinical data (p < 0.05). Results: Adult patients with PKU showed significantly lower performance than HC in Full Scale IQ (t = 2.67; p =.010) from the WAIS-IV. The PKU group also showed significantly lower volumes than HC in the pallidum (U = 224.000; p =.008), hippocampus (U = 243.000; p =.020), amygdala (U = 200.000; p =.002), and brainstem (t = 3.17; p =.006) as well as in total cerebral white matter volume (U = 175.000; p =.001). Blood phenylalanine (Phe) levels in PKU patients were negatively correlated with the pallidum (r = -0.417; p =.013) and brainstem (r = -0.455, p =.006) volumes. Conclusions: Adult patients with early-treated PKU showed significantly lower global intelligence than HC. Moreover, these patients showed reduced global white matter volume as well as reductions in the volume of several subcortical grey matter structures, which might be related to the existence of underlying neurodevelopmental alterations. Higher blood Phe levels were also negatively correlated with pallidum and brainstem, suggesting a higher vulnerability of these structures to Phe toxicity. [ABSTRACT FROM AUTHOR]

This review paper summarizes the observations and results of the Mars Express Mission and its application in the analysis of geological processes and landforms on Mars during the last 20 years. The Mars Express observations provided an extended data base allowing a comparative evaluation of different geological surface landforms and their time-based delimitation. High-resolution imagery and digital elevations models on a local to regional scale and spectral measurements are the basis for geological analyses of water-related surface processes on Mars. This includes the nature and discharges of valley networks, formation timescale of deltas, volumina of sedimentary deposits as well as estimating the age of geological units by crater size–frequency distribution measurements. Both the quantifying of geological processes and the determination of absolute model ages allows to constraint the evolution of Martian water-related activity in space and time. Comparative age estimation of fluvial, glacial, and lacustrine deposits, as well as their timing and episodicity, has revealed the nature and evolution of the Martian surface hydrological cycle. Fluvial and lacustrine activity phases are spread over a time span from Noachian until Amazonian periods, but detailed studies show that they have been interrupted by multiple and long-lasting phases of cessation and quiescent. In addition, evidence of glacial activity shows discrete phases of enhanced intensity correlating with increased spin-axis obliquity amplitude. The episodicity of geological processes, erosion, deposition, and glaciation on Mars demonstrate a close correlation between individual surface processes and endogenic activity as well as spin-axis/orbital variations and changing climate condition. [ABSTRACT FROM AUTHOR]

Chevron-shaped protrusions have been proposed in the literature for turbulent skin friction reduction. However, there is no consensus on the performance of this passive flow control technique; both an increase and a decrease in drag have been observed in previous studies. There is also no experimental evidence to support the working mechanism behind the drag reduction effect that has been postulated in the literature. In this study, direct force measurements were used to replicate experiments from the literature and, in addition, were used to test new array configurations to characterise the effect of individual design parameters on drag performance. A total of 23 different protrusion configurations were investigated in a turbulent boundary layer flow. In addition to the integral force measurements, particle image velocimetry was used to measure wall-parallel velocity fields in order to extract the statistical sizing and energy of the near-wall cycle turbulence. All configurations increased the drag between 2% and 10% for a friction Reynolds number of 1700. The drag reduction reported in the literature could not be replicated; however, these findings agreed with an experimental and numerical study that reported drag increase. The trend observed in the low-speed streak spacing from the PIV experiments was consistent with that observed in the balance data. Nevertheless, no evidence was found to support the working mechanism proposed in the literature. These results cast doubt on the proposed drag reduction potential of chevron-shaped protrusions. In the authors' view, the results of this study strengthen previous conclusions regarding their minor increase in drag. Future studies to further approach a consensus are proposed. [ABSTRACT FROM AUTHOR]

Purpose: To benchmark palliative care practices in neurooncology centers across Germany, evaluating the variability in palliative care integration, timing, and involvement in tumor board discussions. This study aims to identify gaps in care and contribute to the discourse on optimal palliative care strategies. Methods: A survey targeting both German Cancer Society-certified and non-certified university neurooncology centers was conducted to explore palliative care frameworks and practices for neurooncological patients. The survey included questions on palliative care department availability, involvement in tumor boards, timing of palliative care integration, and use of standardized screening tools for assessing palliative burden and psycho-oncological distress. Results: Of 57 centers contacted, 46 responded (81% response rate). Results indicate a dedicated palliative care department in 76.1% of centers, with palliative specialists participating in tumor board discussions at 34.8% of centers. Variability was noted in the initiation of palliative care, with early integration at the diagnosis stage in only 30.4% of centers. The survey highlighted a significant lack of standardized spiritual care assessments and minimal use of advanced care planning. Discrepancies were observed in the documentation and treatment of palliative care symptoms and social complaints, underscoring the need for comprehensive care approaches. Conclusion: The study highlights a diverse landscape of palliative care provision within German neurooncology centers, underscoring the need for more standardized practices and early integration of palliative care. It suggests the necessity for standardized protocols and guidelines to enhance palliative care's quality and uniformity, ultimately improving patient-centered care in neurooncology. [ABSTRACT FROM AUTHOR]

The immune effector mechanisms involved in protecting against severe COVID-19 infection in elderly nursing home residents following vaccination or natural infection are not well understood. Here, we measured SARS-CoV-2 Spike (S)-directed functional antibody responses, including neutralizing antibodies (NtAb) and antibody Fc-mediated NK cell activity (degranulation and IFNγ production), against the Wuhan-Hu-1, BA.4/5 (for NtAb), and Omicron XBB.1.5 variants in elderly nursing home residents (n = 39; median age, 91 years) before and following a third (pre- and post-3D) and a fourth (pre- and post-4D) mRNA COVID-19 vaccine dose. Both 3D and 4D boosted NtAb levels against both (sub)variants. Likewise, 3D and 4D increased the ability of sera to trigger both LAMP1- and IFNγ-producing NK cells, in particular against XBB.1.5. In contrast to NtAb titres, the frequencies of LAMP1- and IFNγ-producing NK cells activated by antibodies binding to Wuhan-Hu-1 and Omicron XBB.1.5 S were comparable at all testing times. Stronger functional antibody responses were observed in vaccine-experienced participants compared to vaccine-naïve at some testing times. These findings can contribute to identifying a reliable correlate of protection in elderly nursing home residents against severe COVID-19 and inform future vaccine strategies in this population group. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to develop a set of criteria and indicators to evaluate the quality of care of patients with head and neck cancer (HNC). Methods: A systematic literature review was conducted to identify valuable criteria/indicators for the assessment of the quality of care in HNC. With the aid of a technical group, a scientific committee of oncologists specialised in HNC used selected criteria to propose indicators that were evaluated with a two-round Delphi method. Indicators on which consensus was achieved were then prioritised by the scientific committee to develop a final set of indicators. Results: We proposed a list of 50 indicators used in the literature or developed by us to be evaluated with a Delphi method. There was consensus on the appropriateness of 47 indicators in the first round; the remaining 3 achieved consensus in the second round. The 50 indicators were scored to prioritise them, leading to a final selection of 29 indicators related to structure (3), process (22), or outcome (4) and covering diagnosis, treatment, follow-up, and health outcomes in patients with HNC. Easy-to-use index cards were developed for each indicator, with their criterion, definition, formula for use in real-world clinical practice, rationale, and acceptable level of attainment. Conclusions: We have developed a set of 29 evidence-based and expert-supported indicators for evaluating the quality of care in HNC, covering diagnosis, treatment, follow-up, and health outcomes. [ABSTRACT FROM AUTHOR]

We study the O(3) critical model and the free theory of a scalar triplet in the presence of a magnetic impurity. We use analytic bootstrap techniques to extract results in the ε-expansion. First, we extend by one order in perturbation theory the computation of the beta function for the defect coupling in the free theory. Then, we analyze in detail the low-lying spectrum of defect operators, focusing on their perturbative realization when the defect is constructed as a path-ordered exponential. After this, we consider two different bulk two-point functions and we compute them using the defect dispersion relation. For a free bulk theory, we are able to fix the form of the correlator at all orders in ε. In particular, taking ε → 1, we can show that in d = 3 one does not have a consistent and non-trivial defect CFT. For an interacting bulk, we compute the correlator up to second order in ε. Expanding these results in the bulk and defect block expansions, we are able to extract an infinite set of defect CFT data. We discuss low-spin ambiguities that affect every result computed through the dispersion relation and we use a combination of consistency conditions and explicit diagrammatic calculations to fix this ambiguity. [ABSTRACT FROM AUTHOR]

Follicular lymphoma (FL), the most common indolent non-Hodgkin lymphoma, constitutes a paradigm of immune tumor microenvironment (TME) contribution to disease onset, progression, and heterogenous clinical outcome. Here we present the first FL-Patient Derived Lymphoma Spheroid (FL-PDLS), including fundamental immune actors and features of TME in FL lymph nodes (LNs). FL-PDLS is organized in disc-shaped 3D structures composed of proliferating B and T cells, together with macrophages with an intermediate M1/M2 phenotype. FL-PDLS recapitulates the most relevant B-cell transcriptional pathways present in FL-LN (proliferation, epigenetic regulation, mTOR, adaptive immune system, among others). The T cell compartment in the FL-PDLS preserves CD4 subsets (follicular helper, regulatory, and follicular regulatory), also encompassing the spectrum of activation/exhaustion phenotypes in CD4 and CD8 populations. Moreover, this system is suitable for chemo and immunotherapy testing, recapitulating results obtained in the clinic. FL-PDLS allowed uncovering that soluble galectin-9 limits rituximab, rituximab, plus nivolumab/TIM-3 antitumoral activities. Blocking galectin-9 improves rituximab efficacy, highlighting galectin-9 as a novel immunotherapeutic target in FL. In conclusion, FL-PDLS maintains the crosstalk between malignant B cells and the immune LN-TME and constitutes a robust and multiplexed pre-clinical tool to perform drug screening in a patient-derived system, advancing toward personalized therapeutic approaches. [ABSTRACT FROM AUTHOR]

Sudden cardiac death in children is a rare event, but of great social significance. Generally, it is related to heart disease with a risk of sudden cardiac death (SCD), which may occur with cardiovascular symptoms and/or electrocardiographic markers; thus, a primary care paediatrician (PCP) could detect them. Therefore, we proposed a study that assesses how to put into practice and conduct a cardiovascular assessment within the routine healthy-child check-ups at six and twelve years of age; that reflects cardiovascular signs and symptoms, as well as the electrocardiographic alterations that children with a risk of SCD in the selected population present; and that assesses the PCP's skill at electrocardiogram (ECG) interpretation. In collaboration with PCPs, primary care nurses, and paediatric cardiologists, an observational, descriptive, multicentre, cross-sectional study was carried out in the Balearic Islands (Spain), from April 2021 to January 2022, inclusive. The PCPs gathered patient data through forms (medical record, electrocardiogram, and physical examination) and sent them to the investigator, together with the informed consent document and electrocardiogram. The investigator passed the electrocardiogram on to the paediatric cardiologists for reading, in an identical form to those the paediatricians had filled in. The variables were collected, and a descriptive analysis performed. Three paediatric cardiologists, twelve PCPs, and nine nurses from seven public health centres took part. They collected the data from 641 patients, but 233 patients did not participate (in 81.11% due to the PCP's workload). Therefore, the study coverage was around 64%, representing the quotient of the total number of patients who participated, divided by the total number of patients who were eligible for the study. We detected 30 patients with electrocardiographic alterations compatible with SCD risk. Nine of these had been examined by a paediatric cardiologist at some time (functional murmur in 8/9), five had reported shortness of breath with exercise, and four had reported a family history of sudden death. The physical examination of all the patients whose ECG was compatible with a risk of SCD was normal. Upon analysing to what extent the ECG results of the PCP and the paediatric cardiologist agreed, the percentage of agreement in the final interpretation (normal/altered) was 91.9%, while Cohen's kappa coefficient was 31.2% (CI 95%: 13.8–48.6%). The sensitivity of the ECG interpretation by the PCP to detect an ECG compatible with a risk of SCD was 29% and the positive predictive value 45%. Conclusions: This study lays the foundations for future SCD risk screening in children, performed by PCPs. However, previously, it would be important to optimise their training in reading and interpreting paediatric ECGs. What is Known: • In Spain at present, there is a programme in place to detect heart disease with a risk of sudden death [1], but it targets only children who are starting on or are doing a physical activity as a federated sport. Implementing such screening programmes has proven effective in several countries [2]. However, several studies showed that the incidence of sudden cardiac death is no higher in children competing in sport activities than in those who do not do any sport [3]. This poses an ethical conflict, because at present, children who do not do any federated sport are excluded from screening. According to the revised literature, so far, only in two studies did they screen the child population at schools, and in both, they successfully detected patients with heart disease associated to the risk of sudden death [4-5]. We have found no studies where the screening of these features was included within the routine healthy-child check-ups by primary care paediatricians. What is New: • We did not know whether—in our setting, at present—the primary care paediatrician could perform a screening method within the routine healthy-child check-ups, in order to detect presumably healthy children at risk of sudden cardiac death, as they present one of the SCD risks. In this regard, we proposed our project: to assess how to put into practice and conduct a cardiovascular assessment via SCD risk screening in the healthy child population by primary care paediatricians and appraise primary care paediatricians' skills in identifying the electrocardiographic alterations associated with SCD risk. The ultimate intention of this pilot study was to make it possible, in the future, to design and justify a study aimed at universalising cardiovascular screening and achieving a long-term decrease in sudden cardiac death events in children. [ABSTRACT FROM AUTHOR]

Abstract Our limited ability to predict genotype–phenotype relationships has called for strategies that allow testing of thousands of hypotheses in parallel. Deep scanning mutagenesis has been successfully implemented to map genotype–phenotype relationships at a single‐protein scale, allowing scientists to elucidate properties that are difficult to predict. However, most phenotypes are dictated by several proteins that are interconnected through complex and robust regulatory and metabolic networks. These sophisticated networks hinder our understanding of the phenotype of interest and limit our capabilities to rewire cellular functions. Here, we leveraged CRISPR‐EnAbled Trackable genome Engineering to attempt a parallel and high‐resolution interrogation of complex networks, deep scanning multiple proteins associated with lysine metabolism in Escherichia coli. We designed over 16,000 mutations to perturb this pathway and mapped their contribution toward resistance to an amino acid analog. By doing so, we identified different routes that can alter pathway function and flux, uncovering mechanisms that would be difficult to rationally design. This approach sets a framework for forward investigation of complex multigenic phenotypes.

This study aims at identifying risk-related patterns of left ventricular contraction dynamics via novel volume transient characterization. A multicenter cohort of AMI survivors (n = 1021) who underwent Cardiac Magnetic Resonance (CMR) after infarction was considered for the study. The clinical endpoint was the 12-month rate of major adverse cardiac events (MACE, n = 73), consisting of all-cause death, reinfarction, and new congestive heart failure. Cardiac function was characterized from CMR in 3 potential directions: by (1) volume temporal transients (i.e. contraction dynamics); (2) feature tracking strain analysis (i.e. bulk tissue peak contraction); and (3) 3D shape analysis (i.e. 3D contraction morphology). A fully automated pipeline was developed to extract conventional and novel artificial-intelligence-derived metrics of cardiac contraction, and their relationship with MACE was investigated. Any of the 3 proposed directions demonstrated its additional prognostic value on top of established CMR indexes, myocardial injury markers, basic characteristics, and cardiovascular risk factors (P < 0.001). The combination of these 3 directions of enhancement towards a final CMR risk model improved MACE prediction by 13% compared to clinical baseline (0.774 (0.771—0.777) vs. 0.683 (0.681—0.685) cross-validated AUC, P < 0.001). The study evidences the contribution of the novel contraction characterization, enabled by a fully automated pipeline, to post-infarction assessment. [ABSTRACT FROM AUTHOR]

In their natural habitats, microbes rarely exist in isolation; instead, they thrive in consortia, where various interactions occur. In this study, a defined synthetic co-culture of the cyanobacterium S. elongatus cscB, which supplies sucrose to the heterotrophic P. putida cscRABY, is investigated to identify potential interactions. Initial experiments reveal a remarkable growth-promoting effect of the heterotrophic partner on the cyanobacterium, resulting in an up to 80% increase in the growth rate and enhanced photosynthetic capacity. Vice versa, the presence of the cyanobacterium has a neutral effect on P. putida cscRABY, highlighting the resilience of pseudomonads against stress and their potential as co-culture partners. Next, a suitable reference process reinforcing the growth-promoting effect is established in a parallel photobioreactor system, which sets the basis for the analysis of the co-culture at the transcriptome, proteome, and metabolome levels. In addition to several moderate changes, including alterations in the metabolism and stress response in both microbes, this comprehensive multi-OMICs approach strongly hints towards the exchange of further molecules beyond the unidirectional feeding with sucrose. Taken together, these findings provide valuable insights into the complex dynamics between both co-culture partners, indicating multi-level interactions, which can be employed for further streamlining of the co-cultivation system. This study investigates interspecies interaction in a synthetic co-culture consisting of the sucrose-secreting cyanobacterium S. elongatus cscB and its sucrose-consuming partner P. putida cscRABY by employing a comprehensive multi-OMICs approach. [ABSTRACT FROM AUTHOR]

Water quality and the management of nitrogenous compounds are of key importance within aquaculture. In this paper, automated and portable analysers for in situ analysis of nitrite and nitrate in water were deployed in freshwater and saline recirculating aquaculture systems (RAS). The analysers were based upon ion chromatography (IC) and employed a NaCl eluent with an anion exchange guard column for low backpressure anion separation, in combination with selective 235 nm ultra-violet light-emitting diode (UV-LED) based absorbance detection. The analysers were monitored and delivered real-time concentration data using a cellular internet of things (IoT) module and cloud-based dashboard. Overall performance and chromatographic repeatability were tested across various temperature profiles and 500 sequential runs within the laboratory. Deployments in freshwater and saline RAS, with concentrations ranging between 0.1–3.6 mg L−1 nitrite and 0.6–392 mg L−1 nitrate, were successful and the analytical performance was comparable to that of accredited lab-based instrumentation. [ABSTRACT FROM AUTHOR]

Purpose: There is an unclear relationship between estradiol levels and fresh embryo transfer (ET) outcomes. We determined the relationship between estradiol on the day of trigger, in fresh ET cycles without premature progesterone elevation, and good birth outcomes (GBO). Methods: We identified autologous fresh ET cycles from 2015 to 2021 at multiple clinics in the USA. Patients with recurrent pregnancy loss, uterine factor, and elevated progesterone on the day of trigger (progesterone > 2 ng/mL or 3-day area under the curve > 4.5 ng/mL) were excluded. The primary outcome was GBO (singleton, term, live birth with appropriate weight). Log-binomial generalized estimating equations determined the likelihood of outcomes. Results: Of 17,608 fresh ET cycles, 5025 (29%) yielded GBO. Cycles with estradiol ≥ 4000 pg/mL had a greater likelihood of GBO compared to cycles < 1000 pg/mL (aRR = 1.32, 95% CI 1.13–1.54). Pairwise comparisons of estradiol between < 1000 pg/mL versus 1000–1999 pg/mL and 1000–1999 pg/mL versus 2000–2999 pg/mL revealed a higher likelihood of GBO with higher estradiol (aRR 0.83, 95% CI 0.73–0.95; aRR 0.91, 95% CI 0.85–0.97, respectively). Comparisons amongst more elevated estradiol levels revealed that the likelihood of GBO remained similar between groups (2000–2999 pg/mL versus 3000–3999 pg/mL, aRR 1.04, 95% CI 0.97–1.11; 3000–3999 pg/mL versus ≥ 4000 pg/mL, aRR 0.96, 95% CI 0.9–1.04). Conclusion: In fresh ET cycles, higher estradiol levels were associated with an increased prevalence of GBO until estradiol 2000–2999 pg/mL, thereafter plateauing. In fresh ET candidates, elevated estradiol levels should not preclude eligibility though premature progesterone rise, and risk of ovarian hyperstimulation syndrome must still be considered. [ABSTRACT FROM AUTHOR]

The search for Skiba points in infinite-time optimal control problems with several steady states is an active research area. In this paper, we apply the backward integration method and show its power and relative simplicity as a tool for this task. We apply the method for the classical model of the economy shallow lake based on the phosphorous dynamics and explicitly compute the optimal trajectories and the Skiba points. We also suggest a more natural welfare function, which takes into account the finite value of any economic resource, and show, again in an explicit manner, that it also possesses Skiba points. [ABSTRACT FROM AUTHOR]

Since the introduction of the Oddy test in 1973, many museums and cultural institutions have put the method in use, developing their own versions and protocols. Currently the 3-in-1 version, temperature at 60 ºC and 2 g of tested material are set as common practice; however, other variables of the test are not standardized. The purpose of this study is to examine current versions of the Oddy test, to identify differences in the results derived from variations in the procedures, and ultimately raising awareness within the conservation community to work together towards a standardized protocol. In this article, we review the available information on the methodological differences in Oddy test protocols published in the literature related to glassware cleaning, coupon preparation, reaction vessel setup and rating of materials. Based on the review, and to highlight the many variables that could affect the results of the test, seven European cultural institutions working under the H2020 IPERION HS project performed a comparative 3-in-1 Oddy test by blindly evaluating the same ten materials. Each institution used its own test methodology but some guidelines were advised: (1) Detergents as a cleaning procedure for glassware, (2) P600 sandpaper or micromesh pad close to 1500 to prepare metal coupons and (3) 1:100 as water–air ratio. Despite this, differences between institutions' results were still observed. Some of them are due to the differences in the coupons preparation, either in the sanding pattern or in the edge area. In order to separate the contribution of the experimental setup and the subjectivity of the evaluation in the discrepancies, coupons from all institutions have been rated by a single team of judges with experience in the Oddy Test. Results show that differences in the evaluation criteria play a relevant role in the discrepancies of the results, especially for institutions with less experience in the test. These results highlight the need to further standardize the methodology and criteria for visual assessment. Nevertheless, the Oddy test has been found to be reliable for the identification of materials that produce emissions hazardous for the conservation of cultural assets. [ABSTRACT FROM AUTHOR]

Phylogenetic analyses over the last two decades have united a few small, and previously orphan clades, the nematodermatids, acoels and xenoturbelids, into the phylum Xenacoelomorpha. Some phylogenetic analyses support a sister relationship between Xenacoelomorpha and Ambulacraria (Xenambulacraria), while others suggest that Xenacoelomorpha may be sister to the rest of the Bilateria (Nephrozoa). An understanding of the cell type complements of Xenacoelomorphs is essential to assessing these alternatives as well as to our broader understanding of bilaterian cell type evolution. Employing whole organism single-cell RNA-seq in the marine xenacoelomorph worm Xenoturbella bocki, we show that Xenambulacrarian nerve nets share regulatory features and a peptidergic identity with those found in cnidarians and protostomes and more broadly share muscle and gland cell similarities with other metazoans. Taken together, these data are consistent with broad homologies of animal gland, muscle, and neurons as well as more specific affinities between Xenoturbella and acoel gut and epidermal tissues, consistent with the monophyly of Xenacoelomorpha. Recent phylogenetic analyses have identified orphan clades, including Xenacoelomorphs, that can offer insights into bilaterian evolution. Here they generate a cell type atlas of Xenoturbella bockithat highlights cellular diversity in the nervous system and other tissues, reinforcing the idea of parallel evolution of cell types across animals. [ABSTRACT FROM AUTHOR]

The impacts of climate change on heritage collections in Mediterranean museums are serious and lead to accelerated material degradation, loss of value, increasing conservation costs and climatisation. Climate change scenarios and simulation models have been developed to predict the extreme and average future environmental conditions and to assess the future long-term risks caused by global warming for museum buildings and their collections in Mediterranean countries, with Egypt being particularly at risk. This paper presents the results of the risk analysis of the indoor and outdoor environments in Alexandria Museum of Fine Arts (AMFA) in Egypt to provide an overview of the current situation of conservation and museum management and to provide evidence-based data to support decision-making regarding preventive conservation given the museum's limited funding, capacity and resources. Unfortunately, the air quality in the museum cannot be considered satisfactory and specific measures need to be taken to improve the level of air quality and museum and building management. The results enabled an assessment of indoor air quality and provided information on potential risks to the museum building and collections, including variations in temperature (T) and relative humidity (RH), concentrations of NO2, SO2, O3, CO2, acetic and formic acid and lighting conditions, as well as the location and management of the museum. The results necessitate the development of a preventive conservation plan to address the challenges associated with high T/RH fluctuations and pollution pressure. This requires more regular use of the HVAC system within certain T/RH set points as well as minimising light exposure and the use of UV-filtering glazing. Care should be taken to ensure that housekeeping and emergency preparedness reduce the damping and salt florescence in the museum building. However, dealing with the impact of climate change on indoor and outdoor environments and museum collections in Mediterranean museums requires a holistic and adaptive approach that includes joint collaboration, research, training and strategic planning to ensure the long-term preservation of valuable cultural heritage collections in different climates with customised adaptations based on local environmental conditions, resources and needs. Resilience planning should be region-specific and take into account the potential impacts of extreme weather events, sea level rise and other climate-related challenges. [ABSTRACT FROM AUTHOR]

Purpose: Unnecessary axillary surgery can potentially be avoided in patients with DCIS undergoing mastectomy. Current guidelines recommend upfront sentinel lymph node biopsy during the index operation due to the potential of upstaging to invasive cancer. This study reviews a single institution's experience with de-escalating axillary surgery using superparamagnetic iron oxide dye for axillary mapping in patients undergoing mastectomy for DCIS. Methods: This is a retrospective single-institution cross-sectional study. All medical records of patients who underwent mastectomy for a diagnosis of DCIS from August 2021 to January 2023 were reviewed and patients who had SPIO injected at the time of the index mastectomy were included in the study. Descriptive statistics of demographics, clinical information, pathology results, and interval sentinel lymph node biopsy were performed. Results: A total of 41 participants underwent 45 mastectomies for DCIS. The median age of the participants was 58 years (IQR = 17; range 25 to 76 years), and the majority of participants were female (97.8%). The most common indication for mastectomy was diffuse extent of disease (31.7%). On final pathology, 75.6% (34/45) of mastectomy specimens had DCIS without any type of invasion and 15.6% (7/45) had invasive cancer. Of the 7 cases with upgrade to invasive disease, 2 (28.6%) of them underwent interval sentinel lymph node biopsy. All sentinel lymph nodes biopsied were negative for cancer. Conclusion: The use of superparamagnetic iron oxide dye can prevent unnecessary axillary surgery in patients with DCIS undergoing mastectomy. [ABSTRACT FROM AUTHOR]

In this paper, we study the asymptotic behavior of the stationary 3D magneto-micropolar fluid flow through a thin domain, whose thickness is given by a parameter 0 < ε ≪ 1 . Assuming that the magnetic Reynolds number is written in terms of the thickness ε , we prove that there exists a critical magnetic Reynolds number, namely R e m c = ε - 2 , such that for every magnetic Reynolds number R e m with order smaller or equal than R e m c , the magneto-micropolar fluid flow in the thin domain can be modeled asymptotically when ε tends to zero by a 2D Reynolds-like model, whose expression is also given. [ABSTRACT FROM AUTHOR]

The Streptococcus pneumoniae bacteria has over 100 known serotypes that display a continuous change in prevalence by patients' age and geographical location and therefore necessitate continued efforts toward development of new vaccines with broader protection. Glycoconjugate vaccines have been instrumental in reducing global morbidity and mortality caused by Streptococcus pneumoniae infections. In these vaccines, the bacterial polysaccharide is conjugated to a carrier protein to enhance immunogenicity. To ensure well defined immunogenicity and stability of conjugated vaccines, reliable quantification of non-conjugated (free) polysaccharide is a critical, albeit challenging step during vaccine clinical dosing, release and stability monitoring. Multivalent preparations of Cross-reactive material 197 (CRM197)- conjugated pneumococcal polysaccharide materials often contain only nanogram levels of each individual free polysaccharide at final container concentrations. We have developed a novel method for the separation of free polysaccharides from conjugated material that requires no sample derivatization, employing instead an approach of quantitative immunoprecipitation of CRM197 with 3 different monoclonal antibodies and magnetic beads. A mix of antibodies against both linear and conformational epitopes enables successful removal of conjugates regardless of the protein folded state. The remaining free polysaccharide is subsequently measured in a serotype-specific ELISA. [ABSTRACT FROM AUTHOR]

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In the ageing process, the vascular system undergoes morphological and functional changes that may condition brain functioning; for this reason, the aims of this study were to assess the effect of vascular function indirectly measured by ankle-brachial index (ABI) on both cognitive performance at baseline and change in cognitive performance at end of follow-up. We developed a prospective, population-based, cohort study with 1147 participants aged > 65 years obtained from the Toledo Study for Healthy Ageing who had cognitive assessment and measured ABI in the first wave (2006–2009) were selected for the cross-sectional analysis. Those participants who also performed the cognitive assessment in the second wave (2011–2013) were selected for the prospective analysis. Cognitive impairment diagnosis and symptoms and/or history of cardio/neurovascular disease were used as exclusion criteria. Multivariate segmented regression model was used to assess the associations between ABI and cognitive performance in both the cross-sectional and prospective analyses. As ABI score decreased from 1.4, the cross-sectional analysis showed a higher decrease in cognitive performance and the prospective analysis showed a higher degree of worsening in cognitive performance. Our findings suggest that the ABI, a widespread measure of vascular health in primary care, may be a useful tool for predicting cognitive performance and its evolution. [ABSTRACT FROM AUTHOR]