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Reliable quantitative vegetation reconstructions for Europe during the Holocene are crucial to improving our understanding of landscape dynamics, making it possible to assess the past effects of environmental variables and land-use change on ecosystems and biodiversity, and mitigating their effects in the future. We present here the most spatially extensive and temporally continuous pollen-based reconstructions of plant cover in Europe (at a spatial resolution of 1° × 1°) over the Holocene (last 11.7 ka BP) using the ‘Regional Estimates of VEgetation Abundance from Large Sites’ (REVEALS) model. This study has three main aims. First, to present the most accurate and reliable generation of REVEALS reconstructions across Europe so far. This has been achieved by including a larger number of pollen records compared to former analyses, in particular from the Mediterranean area. Second, to discuss methodological issues in the quantification of past land cover by using alternative datasets of relative pollen productivities (RPPs), one of the key input parameters of REVEALS, to test model sensitivity. Finally, to validate our reconstructions with the global forest change dataset. The results suggest that the RPPs.st1 (31 taxa) dataset is best suited to producing regional vegetation cover estimates for Europe. These reconstructions offer a long-term perspective providing unique possibilities to explore spatial-temporal changes in past land cover and biodiversity.

Tumor microenvironments (TMEs) are composed of cancer cells, fibroblasts, extracellular matrix, microvessels, and endothelial cells. Two prolyl endopeptidases, fibroblast activation protein (FAP) and prolyl oligopeptidase (POP), are commonly overexpressed by epithelial-derived malignancies, with the specificity of FAP expression by cancer stromal fibroblasts suggesting FAP as a possible therapeutic target. Despite overexpression in most cancers and having a role in angiogenesis, inhibition of POP activity has received little attention as an approach to quench tumor growth. We developed two specific and highly effective pseudopeptide inhibitors, M83, which inhibits FAP and POP proteinase activities, and J94, which inhibits only POP. Both suppressed human colon cancer xenograft growth >90% in mice. By immunohistochemical stains, M83- and J94-treated tumors had fewer microvessels, and apoptotic areas were apparent in both. In response to M83, but not J94, disordered collagen accumulations were observed. Neither M83- nor J94-treated mice manifested changes in behavior, weight, or gastrointestinal function. Tumor growth suppression was more extensive than noted with recently reported efforts by others to inhibit FAP proteinase function or reduce FAP expression. Diminished angiogenesis and the accompanying profound reduction in tumor growth suggest that inhibition of either FAP or POP may offer new therapeutic approaches that directly target TMEs.

The greater sage-grouse (Centrocercus urophasianus) has been the subject of multiple status reviews under the Endangered Species Act (ESA). Wyoming accounts for approximately 38% of the range-wide population. Since 2000, 2 statewide and 8 local citizen working groups have been established in Wyoming to developed conservation plans and advise state policy. The first statewide plan for the conservation of sage-grouse was formally adopted in 2003. The statewide plan established local sage-grouse working groups charged with developing and facilitating implementation of local conservation plans. Those 8 plans were completed in 2007 and 2008, and updated in 2014. From 2005-2017, the local working groups allocated nearly $7 million in legislatively appropriated funds to support conservation projects. In 2007, then Wyoming governor Dave Freudenthal appointed a statewide Sage-grouse Implementation Team. The team was statutorily sanctioned by the Wyoming legislature in 2015 and advises the current governor on all matters related to the Wyoming Greater Sage-Grouse Core Area Protection Policy. The Core Area Policy was established by Executive Order and provides mechanisms for limiting human disturbance in the most important sage-grouse habitats. Federal land management agencies have incorporated most aspects of the Core Area Policy into their land use planning decisions. Effectiveness of local and state-wide collaborative conservation has been evaluated through assessments of local working group accomplishments, research on policy effectiveness, sage-grouse population monitoring, and ESA status reviews.

Recent evidence indicates that perinatal exposure to maternal obesity, metabolic disease, including diabetes and hypertension, and unhealthy maternal diet has a long-term impact on offspring behavior and physiology. During the past three decades, the prevalence of both obesity and neuropsychiatric disorders has rapidly increased. Epidemiologic studies provide evidence that maternal obesity and metabolic complications increase the risk of attention deficit hyperactivity disorder, autism spectrum disorders, anxiety, depression, schizophrenia, eating disorders (food addiction, anorexia nervosa, and bulimia nervosa), and cognition in offspring. Animal models of maternal high-fat diet induced obesity also document persistent changes in offspring behavior and impairments in critical neural circuitry. Animals exposed to maternal obesity and high-fat diet consumption display impairments in hyperactivity, social behavior, increased anxiety-like and depressive-like behaviors, substance addiction, food addiction, and diminished cognition. During development, these offspring are exposed to elevated levels of nutrients (fatty acids, glucose), hormones (leptin, insulin), and inflammatory factors (C-reactive protein, interleukin, and tumor necrosis factor). Such factors appear to permanently change neuroendocrine regulation and brain development in offspring. In addition, inflammation of the offspring brain during gestation impairs the development of neural pathways critical in the regulation of behavior, such as serotoninergic, dopaminergic, and melanocortinergic. Dysregulation of these circuits increases the risk of mental health disorders. Given the high rates of obesity in most developed nations, it is critical that the mechanisms by which maternal obesity programs offspring behavioral are thoroughly characterized. Such knowledge will be critical in the development of preventative strategies and therapeutic interventions.

Community-associated methicillin-resistant Staphylococcus aureus (MRSA) was first reported in Western Australia in the early 1990s from indigenous peoples living in remote areas. Although a statewide policy of screening all hospital patients and staff who have lived outside the state for MRSA has prevented the establishment of multidrug-resistant epidemic MRSA, the policy has not prevented SCCmec type IV and type V MRSA clones from becoming established. Of the 4,099 MRSA isolates analyzed (referred to the Gram-positive Bacteria Typing and Research Unit) from July 2003 to December 2004, 77.5% were community-associated MRSA (CA-MRSA). Using multilocus sequence/staphylococcal chromosome cassette mec typing, 22 CA-MRSA clones were characterized. Of these isolates, 55.5% were resistant to >1 non–β-lactam antimicrobial drug. Five Panton-Valentine leukocidin (PVL)–positive CA-MRSA clones were identified. The emergence of multidrug-resistant CA-MRSA clones and the detection of PVL toxin genes in clones previously reported as PVL negative is a major public health concern.

In Australia the PVL-positive ST93-IV [2B], colloquially known as "Queensland CA-MRSA" has become the dominant CA-MRSA clone. First described in the early 2000s, ST93-IV [2B] is associated with skin and severe invasive infections including necrotizing pneumonia. A singleton by multilocus sequence typing (MLST) eBURST analysis ST93 is distinct from other S. aureus clones. To determine if the increased prevalence of ST93-IV [2B] is due to the widespread transmission of a single strain of ST93-IV [2B] the genetic relatedness of 58 S. aureus ST93 isolated throughout Australia over an extended period were studied in detail using a variety of molecular methods including pulsed-field gel electrophoresis, spa typing, MLST, microarray DNA, SCCmec typing and dru typing. Identification of the phage harbouring the lukS-PV/lukF-PV Panton Valentine leucocidin genes, detection of allelic variations in lukS-PV/lukF-PV, and quantification of LukF-PV expression was also performed. Although ST93-IV [2B] is known to have an apparent enhanced clinical virulence, the isolates harboured few known virulence determinants. All PVL-positive isolates carried the PVL-encoding phage ΦSa2USA and the lukS-PV/lukF-PV genes had the same R variant SNP profile. The isolates produced similar expression levels of LukF-PV. Although multiple rearrangements of the spa sequence have occurred, the core genome in ST93 is very stable. The emergence of ST93-MRSA is due to independent acquisitions of different dru-defined type IV and type V SCCmec elements in several spa-defined ST93-MSSA backgrounds. Rearrangement of the spa sequence in ST93-MRSA has subsequently occurred in some of these strains. Although multiple ST93-MRSA strains were characterised, little genetic diversity was identified for most isolates, with PVL-positive ST93-IVa [2B]-t202-dt10 predominant across Australia. Whether ST93-IVa [2B] t202-dt10 arose from one PVL-positive ST93-MSSA-t202, or by independent acquisitions of SCCmec-IVa [2B]-dt10 into multiple PVL-positive ST93-MSSA-t202 strains is not known.

A number of experimental studies have been conducted to determine the atmospheric oxidation of tetrachloroethylene, many indicating phosgene as the major product. Although various mechanisms have been suggested, the mechanism of phosgene production is unclear. Additionally, confusion has arisen over the role chlorine atoms may play in the oxidation of tetrachloroethylene and the products produced. To clarify these points, this study presents a comprehensive computational study of both the hydroxyl radical and the chlorine atom initiated atmospheric oxidation mechanism of tetrachloroethylene. The energetics for the oxidation of tetrachloroethylene (C2Cl4) are computed using ab initiomethods. Potential energy surfaces of the reaction pathways are determined from the computations. This study clarifies the involvement of the Cl-initiated reaction pathways in the oxidation of tetrachloroethylene. Results from this work suggest that the final products are primarily from the Cl-initiated oxidation and include: trichloroacetyl chloride [ClC(O)CCl3], phosgene [C(O)Cl2], and regeneration of the initiating chlorine atom. [ABSTRACT FROM AUTHOR]

Abstract  A total of 123 pigeonpea landraces collected from farmers’ fields in four pigeonpea growing regions of Tanzania were characterized and evaluated for 16 qualitative and 14 quantitative descriptors, and their response across three pigeonpea growing environments in Tanzania and Kenya determined. Polymorphism in the qualitative traits was relatively low among accessions and across collection regions. Collections from the northern highlands exhibited lower diversity in qualitative descriptors, especially physical grain characters, relative to the other three regions, an indication of farmer selection in response to market preferences. There were significant differences in agronomic traits among accessions and in genotype-by-environment interaction (GEI). High broad-sense heritability was recorded for days to flower, days to maturity, plant height, raceme number and 100 seed mass. Principal component analysis and clustering separated variability among the accessions according to days to flower, days to maturity, plant height, number of primary and secondary branches, and number of racemes per plant. There was close clustering within and between materials from the coastal zone, eastern plains and southern plains with the northern accessions distinctly separated and with wide dispersion within them. Overall, two diversity clusters were evident with coastal, eastern and southern landraces in one diversity cluster and northern highlands landraces in another cluster. This diversity grouping established potential heterotic groups which may be used in crosses to generate new cultivars adapted to different pigeonpea growing environments with consumer acceptability. The grouping may also form a basis of forming a core collection of this germplasm representing the variability available. [ABSTRACT FROM AUTHOR]

A field experiment was conducted in Tanzania for two seasons to assess the genetic diversity of bambara groundnut landraces based on morphological characters. One hundred accessions collected from a wide range of agricultural zones in the country were evaluated in a 10 × 10 triple lattice block design at Maruku station in Bukoba, Tanzania. For the qualitative characters evaluated, considerable morphological variations were observed for growth habit, pod shape and pod colour. Quantitative morphological characters such as peduncle length, number of leaves per plant, terminal leaflet width, terminal leaflet length, petiole length, plant spread, plant length, pod width, seed length, seed width, number of pods per plant, shelling percentage and days to 50% flowering showed significant variation among accessions for the two test seasons. Multivariate analysis for 15 quantitative morphological traits that showed significant variation indicated that the first four PCs with eigenvalues ≥1 accounted for 63.0 and 65.0% of the total variance among the accessions during the two test seasons, respectively. The most important loadings for PC1 and PC2 for the two seasons were terminal leaflet width, terminal leaflet length, petiole length, plant spread, plant height and pod length, pod width, seed length, seed width, numbers of pods per plant. Cluster analysis grouped bambara groundnut accessions into three major groups with respect to their geographic origins. Based on this present study, bambara groundnut landraces from Tanzania displayed a considerable diversity for morphological and agronomic traits useful for germplasm management and utilization into crop improvement. [ABSTRACT FROM AUTHOR]

Landraces of pigeonpea (Cajanus cajan (L.) Millsp.) were collected from farmer's fields in its major cropping areas in Tanzania. Passport data, including descriptors, information on cultural practices and uses were recorded. Pigeonpea intercropping with maize, sorghum and cassava were found to be the dominating cropping systems, with characteristic differences between regions. In the northern part of the country pigeonpea has been developed into a relatively high yielding cash crop. Also in part of the Coastal Zone and Eastern Plain a market, particularly for green pods, have been developed. It is also in these areas near Dar es Salam that pigeonpea is most frequently found as a garden crop. [ABSTRACT FROM AUTHOR]

Sacral nerve stimulation is an emerging surgical technique that uses chronic low-level electrical stimulation, applied to the nerves of the sacral plexus, to produce a clinically beneficial physiological effect on the lower bowel, pelvic floor and anal canal. Faecal incontinence is common, maximal conservative therapy may improve some patients but many require surgery. Results are variable and often unsatisfactory and further options are limited, the traditional end-point being the formation of a colostomy. Sacral nerve stimulation appears to be an alternative treatment that is successful, has low morbidity, is maintained in the medium term and associated with an improved quality of life. The technique has the advantage of a minimally invasive test procedure with high predictive value and the surgery is minor. The underlying mechanism of action although predominately neurological in nature remains to be determined. Precise patient selection is currently unclear however, results are superior to other techniques. [ABSTRACT FROM AUTHOR]

Upconversion of sunlight with energy below the band gap of a solar cell is a promising technique for enhancing the cell efficiency, simply by utilizing a larger part of the solar spectrum. The present topical review addresses this concept and discusses the material properties needed for an efficient upconversion process with focus on both silicon and organic solar cells. To design efficient upconverters, insight into topics such as quantum-optics, nano-optics, numerical modeling, optimization, material fabrication, and material characterization is paramount, and the necessary concepts are introduced throughout the review. Upconversion modeling is done using rate equations, while optical modeling is done by solving Maxwell’s equations using the finite element method. Topology optimization is introduced and used to generate geometries of gold nanoparticles capable of greatly enhancing the upconversion yield. Fabrication and experimental characterization methods are discussed. Some recent results are presented and finally the possibility of designing upconverting materials capable of increasing the short-circuit current in a solar cell is discussed. [ABSTRACT FROM AUTHOR]

Abstract Background Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic disease that arises from TSC1 or TSC2 genetic mutations. These genetic mutations can induce the development of benign tumors in any organ system with significant clinical implications in morbidity and mortality. In rare instances, patients with TSC can have malignant tumors, including renal cell carcinoma (RCC) and pancreatic neuroendocrine tumor (PNET). It is considered a hereditary renal cancer syndrome despite the low incidence of RCC in TSC patients. TSC is typically diagnosed in prenatal and pediatric patients and frequently associated with neurocognitive disorders and seizures, which are often experienced early in life. However, penetrance and expressivity of TSC mutations are highly variable. Herein, we present a case report, with associated literature, to highlight that there exist undiagnosed adult patients with less penetrant features, whose clinical presentation may contain non-classical signs and symptoms, who have pathogenic TSC mutations. Case presentation A 31-year-old female with past medical history of leiomyomas status post myomectomy presented to the emergency department for a hemorrhagic adnexal cyst. Imaging incidentally identified a renal mass suspicious for RCC. Out of concern for hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome, the mass was surgically removed and confirmed as RCC. Discussion with medical genetics ascertained a family history of kidney cancer and nephrectomy procedures and a patient history of ungual fibromas on the toes. Genetic testing for hereditary kidney cancer revealed a 5’UTR deletion in the TSC1 gene, leading to a diagnosis of TSC. Following the diagnosis, dermatology found benign skin findings consistent with TSC. About six months after the incidental finding of RCC, a PNET in the pancreatic body/tail was incidentally found on chest CT imaging, which was removed and determined to be a well-differentiated PNET. Later, a brain MRI revealed two small cortical tubers, one in each frontal lobe, that were asymptomatic; the patient’s history and family history did not contain seizures or learning delays. The patient presently shows no evidence of recurrence or metastatic disease, and no additional malignant tumors have been identified. Conclusions To our knowledge, this is the first report in the literature of a TSC patient without a history of neurocognitive disorders with RCC and PNET, both independently rare occurrences in TSC. The patient had a strong family history of renal disease, including RCC, and had several other clinical manifestations of TSC, including skin and brain findings. The incidental finding and surgical removal of RCC prompted the genetic evaluation and diagnosis of TSC, leading to a comparably late diagnosis for this patient. Reporting the broad spectrum of disease for TSC, including more malignant phenotypes such as the one seen in our patient, can help healthcare providers better identify patients who need genetic evaluation and additional medical care.

Summary: During metastasis, tumor cells invade through the basement membrane and intravasate into blood vessels and then extravasate into distant organs to establish metastases. Here, we report a critical role of a transmembrane serine protease fibroblast activation protein (FAP) in tumor metastasis. Expression of FAP and TWIST1, a metastasis driver, is significantly correlated in several types of human carcinomas, and FAP is required for TWIST1-induced breast cancer metastasis to the lung. Mechanistically, FAP is localized at invadopodia and required for invadopodia-mediated extracellular matrix degradation independent of its proteolytic activity. Live cell imaging shows that association of invadopodia precursors with FAP at the cell membrane promotes the stabilization and growth of invadopodia precursors into mature invadopodia. Together, our study identified FAP as a functional target of TWIST1 in driving tumor metastasis via promoting invadopodia-mediated matrix degradation and uncovered a proteolytic activity-independent role of FAP in stabilizing invadopodia precursors for maturation.

This paper gives a mathematical exposition of a formula for the scattering matrix for a manifold with infinite cylindrical ends or a waveguide. This formula is well known in the physics literature and we show that a variant of this formula gives the scattering matrix of the mathematics literature. Moreover, we bound the difference between the scattering matrix and an approximation of it computed using a finite rank approximation of the interaction matrix. [ABSTRACT FROM AUTHOR]

Abstract Background It is unclear if state laws supporting breastfeeding are associated with exclusive breastfeeding (EBF) practice among low-income mothers participating in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). The main objectives of our study were to assess the relationship between such laws and EBF among WIC-participating mothers and to assess whether this association varied by employment status. We also assessed how mother’s exposure to WIC breastfeeding consultation was associated with EBF. Methods A cross-sectional study was conducted across seven WIC program locations (i.e., Georgia, Massachusetts, Nevada, Pennsylvania, Wisconsin, Wyoming, Chickasaw Nation) between July–August 2020. Data were collected using convenient sampling from each program location and surveys were administered electronically or on paper to WIC-participating mothers. We restricted our analysis to data from 1161 WIC-participating mothers with infants aged zero to five months old. Multivariable mixed models were used to estimate the relationship between our exposures of interest (i.e., number of laws supporting breastfeeding, employment-related breastfeeding laws, WIC breastfeeding consultation) and EBF, while controlling for potential confounders and accounting for clustering by program location. Effect modification by employment status was assessed on the additive and multiplicative scales. Results Among WIC-participating mothers living in program locations with no employment-related breastfeeding laws, EBF was 26% less prevalent for employed mothers compared to unemployed mothers (adjusted prevalence ratios [aPR]: 0.74, 95% CI: 0.67,0.83). Among all mothers, a one-unit increase in laws supporting breastfeeding was not associated with EBF (aPR: 0.88, 95% CI: 0.71,1.10). However, among employed mothers, living in areas with more employment-related laws was associated with a higher prevalence of EBF (aPR: 1.43, 95% CI: 0.83, 2.44). Infants whose mothers received a WIC breastfeeding consultation had 33% higher prevalence of being exclusively breastfed compared to infants whose mothers did not receive a WIC breastfeeding consultation (aPR: 1.33, 95% CI: 1.05,1.70). Conclusions Infants whose WIC-participating mothers were employed, were less likely to be exclusively breastfed, but our effect modification analyses showed that laws supporting breastfeeding at the workplace may promote EBF among employed women. EBF was more prevalent among mothers who received a WIC breastfeeding consultation compared to those who did not receive such a consultation.

IntroductionCurrent evidence shows that serum miR-371a-3p can identify disease recurrence in testicular germ cell tumour (TGCT) patients and correlates with tumour load. Despite convincing evidence showing the advantages of including miR-371a-3p testing to complement and overcome the classical serum tumour markers limitations, the successful introduction of a serum miRNA based test into clinical practice has been impeded by a lack of consensus regarding optimal methodologies and lack of a universal protocol and thresholds. Herein, we investigate two quantitative real-time PCR (qRT-PCR) based pipelines in detecting disease recurrence in stage I TGCT patients under active surveillance, and compare the sensitivity and specificity for each method.MethodsSequential serum samples collected from 33 stage I TGCT patients undergoing active surveillance were analysed for miR-371a-3p via qRT-PCR with and without an amplification step included.ResultsUsing a pre-amplified protocol, all known recurrences were detected via elevated miR-371a-3p expression, while without pre-amplification, we failed to detect recurrence in 3/10 known recurrence patients. For pre-amplified analysis, sensitivity and specificity was 90% and 94.4% respectively. Without amplification, sensitivity dropped to 60%, but exhibited 100% specificity.DiscussionWe conclude that incorporating pre-amplification increases sensitivity of miR-371a-3p detection, but produces more false positive results. The ideal protocol for quantification of miR-371a-3p still needs to be determined. TGCT patients undergoing active surveillance may benefit from serum miR-371a-3p quantification with earlier detection of recurrences compared to current standard methods. However, larger cross-institutional studies where samples are processed and data is analysed in a standardised manner are required prior to its routine clinical implementation.

Fibroblast activation protein (FAP), a membrane prolyl-specific proteinase with both dipeptidase and endopeptidase activities, is overexpressed by reactive stromal fibroblasts during epithelial-derived cancer growth. FAP digests extracellular matrix as tissue is remodeled during cancer expansion and may also promote an immunotolerant tumor microenvironment. Recent studies suggest that nonspecific FAP inhibitors suppress human cancer xenografts in mouse models. Prolyl oligopeptidase (POP), another prolyl-specific serine proteinase, is also elevated in many cancers and may have a regulatory role in angiogenesis promotion. FAP and POP cell-associated activities may be targets for diagnosis and treatment of various cancers, but their accessibilities to highly effective specific inhibitors have not been shown for cells important to cancer growth. Despite their frequent simultaneous expression in many cancers and their overlapping activities toward commonly used substrates, precise, separate measurement of FAP or POP activity has largely been ignored. To distinguish each of the two activities, we synthesized highly specific substrates and inhibitors for FAP or POP based on amino acid sequences surrounding the scissile bonds of their respective putative substrates. We found varying amounts of FAP and POP protein and activities on activated fibroblasts, mesenchymal cells, normal breast cells, and one breast cancer cell line, with some cells exhibiting more POP than FAP activity. Replicating endothelial cells (ECs) expressed POP but not FAP until tubulogenesis began. Targeting FAP-positive cells, especially mesenchymal stem cells and cancer-associated fibroblasts for inactivation or destruction, and inhibiting POP-producing EC may abrogate stromal invasion and angiogenesis simultaneously and thereby diminish cancer growth.

The lymphatic vascular system plays an active role in immune cell trafficking, inflammation and cancer spread. In order to provide an in vivo tool to improve our understanding of lymphatic vessel function in physiological and pathological conditions, we generated and characterized a tdTomato reporter mouse and crossed it with a mouse line expressing Cre recombinase under the control of the lymphatic specific promoter Prox1 in an inducible fashion. We found that the tdTomato fluorescent signal recapitulates the expression pattern of Prox1 in lymphatic vessels and other known Prox1-expressing organs. Importantly, tdTomato co-localized with the lymphatic markers Prox1, LYVE-1 and podoplanin as assessed by whole-mount immunofluorescence and FACS analysis. The tdTomato reporter was brighter than a previously established red fluorescent reporter line. We confirmed the applicability of this animal model to intravital microscopy of dendritic cell migration into and within lymphatic vessels, and to fluorescence-activated single cell analysis of lymphatic endothelial cells. Additionally, we were able to describe the early morphological changes of the lymphatic vasculature upon induction of skin inflammation. The Prox1-Cre-tdTomato reporter mouse thus shows great potential for lymphatic research.

BACKGROUND: Bacterial pneumonia is a well described complication of influenza. In recent years, community-onset methicillin-resistant Staphylococcus aureus (cMRSA) infection has emerged as a contributor to morbidity and mortality in patients with influenza. Since the emergence and rapid dissemination of pandemic A(H1N1)2009 influenzavirus in April 2009, initial descriptions of the clinical features of patients hospitalized with pneumonia have contained few details of patients with bacterial co-infection. METHODOLOGY/PRINCIPAL FINDINGS: Patients with community-acquired pneumonia (CAP) caused by co-infection with pandemic A(H1N1)2009 influenzavirus and cMRSA were prospectively identified at two tertiary hospitals in one Australian city during July to September 2009, the period of intense influenza activity in our region. Detailed characterization of the cMRSA isolates was performed. 252 patients with pandemic A(H1N1)2009 influenzavirus infection were admitted at the two sites during the period of study. Three cases of CAP due to pandemic A(H1N1)2009/cMRSA co-infection were identified. The clinical features of these patients were typical of those with S. aureus co-infection or sequential infection following influenza. The 3 patients received appropriate empiric therapy for influenza, but inappropriate empiric therapy for cMRSA infection; all 3 survived. In addition, 2 fatal cases of CAP caused by pandemic A(H1N1)2009/cMRSA co-infection were identified on post-mortem examination. The cMRSA infections were caused by three different cMRSA clones, only one of which contained genes for Panton-Valentine Leukocidin (PVL). CONCLUSIONS/SIGNIFICANCE: Clinicians managing patients with pandemic A(H1N1)2009 influenzavirus infection should be alert to the possibility of co-infection or sequential infection with virulent, antimicrobial-resistant bacterial pathogens such as cMRSA. PVL toxin is not necessary for the development of cMRSA pneumonia in the setting of pandemic A( H1N1) 2009 influenzavirus co-infection.

Background: Dermatological health-related quality of life (HRQoL) in solid organ transplant recipients (SOTRs), often affected by skin cancer, has been insufficiently explored. This study aimed to evaluate the impact of skin cancer on quality of life (QoL) in SOTRs and to compare HRQoL measures between SOTRs with and without skin cancer., Methods: This cross-sectional study (June 2023-March 2024) assessed adult SOTRs using the Dermatology Life Quality Index (DLQI) and Skindex-29 questionnaires. For SOTRs with keratinocyte carcinoma (KC), the Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) questionnaire was also administered., Results: A total of 150 adult SOTRs were included, with 82 having developed post-transplant skin cancer, including melanoma and KCs. DLQI scores were higher in SOTRs with skin cancer, however, the difference was not statistically significant (P ≥ 0.065). SOTRs with skin cancer had higher total Skindex-29 scores (P = 0.012) and "emotion" subscale scores (P = 0.0049), indicating a negative impact on QoL. BaSQoL scores showed a moderate negative effect on QoL, with a higher number of KCs correlating with lower QoL (P < 0.05). Female gender was associated with higher DLQI and BaSQoL diagnosis and treatment scores (P < 0.05)., Conclusions: SOTRs with skin cancer had lower QoL, with greater cancer burden linked to worse outcomes. Female gender was also associated with lower QoL. Tailored management strategies are crucial for this population., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Aging is associated with the potential onset of vision and hearing problems, affecting the quality of life and functional independence of older adults. This study sought to investigate the prevalence of various vision and hearing problems in 76-year-old Faroese individuals and examine possible regional variations in these health issues., Materials and Methods: A cross-sectional study design was used, surveying 175 participants, all 76-year-olds, from different regions in the Faroe Islands. Data were collected on demographics, educational level, and marital status, as well as seven indicators of vision problems and eight indicators of hearing problems. Differences by gender and region were tested by Pearson chi squared test and Fisher's exact test, Bonferroni corrected for multiple comparisons., Results: Problems with seeing and hearing were widespread, difficulty reading small print was reported by 58% of participants, and 51% reported less than "good" hearing. Despite the high prevalence of issues, no significant difference was found between genders in terms of problem frequency., Conclusion: This study underscores the high prevalence of vision and hearing issues among 76-year-old Faroese individuals, with no gender differences observed. The detected regional variations necessitate further investigation to better understand and address these health issues in older adults. Policymakers and health professionals should consider these findings in designing interventions to improve older adults' sensory health., Competing Interests: The authors report no conflicts of interest in this work., (© 2025 Haanes et al.)

Afforestation is increasingly recognized as a critical strategy to restore ecosystems and enhance biodiversity on post-agricultural landscapes. However, agricultural legacies, such as altered soil structure, nutrient imbalances, and depleted microbial diversity, can slow down forest establishment or cause ecosystems to deviate from expected successional trajectories. In this opinion paper, we explore the potential of soil inoculations as a tool to overcome these challenges by introducing beneficial microbial communities that can accelerate ecosystem recovery and forest development. Restoring soil biodiversity is a crucial aspect of this process that drives broader ecosystem functionality and resilience. We highlight the need to carefully consider the type and timing of inoculations and to ensure compatibility between the inoculum and recipient site characteristics to optimize the establishment of introduced species. While tree productivity is often a central focus of afforestation efforts, the restoration of soil biodiversity, which will also contribute to increased ecosystem-level functions, should also be a priority for long-term forest resilience. Agricultural legacies add complexities to the restoration process, creating unique challenges that need to be addressed in restoration planning. Thus, successful inoculation strategies require a thorough understanding of both donor and recipient site characteristics, also in relation to potential mismatches related to soil physiochemical properties to avoid unintended consequences such as the non-establishment of introduced species. Additionally, we call for the re-evaluation of afforestation targets and the development of standardized monitoring protocols that track the success of inoculation efforts, particularly regarding soil health, microbial community establishment, and biodiversity recovery. By integrating inoculation practices within a broader restoration framework, we can enhance the resilience, biodiversity, and ecosystem functionality of newly afforested landscapes. Ultimately, this approach may play a critical role in ensuring the success of large-scale afforestation projects., (© 2025 John Wiley & Sons Ltd.)

Treating cartilage damage is challenging as its ability for self-regeneration is limited. Left untreated, it can progress to osteoarthritis (OA), a joint disorder characterized by the deterioration of articular cartilage and other joint tissues. Surgical options, such as microfracture and cell/tissue transplantation, have shown promise as techniques to harness the body's endogenous regenerative capabilities to promote cartilage repair. Nonetheless, these techniques have been scrutinized due to reported inconsistencies in long-term outcomes and the tendency for the defects to regenerate as fibrocartilage instead of the smooth hyaline cartilage native to joint surfaces. Orthobiologics are medical therapies that utilize biologically derived substances to augment musculoskeletal healing. These treatments are rising in popularity because of their potential to enhance surgical standards of care. More recent developments in orthobiologics have focused on the role of exosomes in articular cartilage repair. Exosomes are nano-sized extracellular vesicles containing cargo such as proteins, lipids, and nucleic acids, and are known to facilitate intercellular communication, though their regenerative potential still needs to be fully understood. This review aims to demonstrate the advancements in cartilage regeneration, highlight surgical and biological treatment options, and discuss the recent strides in understanding the precise mechanisms of action involved.

One of the primary indicators of this condition is a painful and migratory dermatitis. Additionally, early signs often include weight loss and diabetes. Patients with glucagonoma commonly first encounter general practitioners or dermatologists. Unfortunately, due to the nonspecific nature of symptoms such as eczema-like dermatitis, weight loss and diabetes, diagnosis is frequently delayed, often by 2-3 years. Consequently, by the time patients are diagnosed, the tumor has usually grown and metastasized, often spreading to the liver. As a result, surgical intervention is often not possible, and treatment options are usually limited to palliative care. However, with early diagnosis of glucagonoma, treatment can be curative. Therefore, it is crucial for medical professionals who initially meet these patients, including dermatologists, general practitioners, endocrinologists, and others, to be aware of this condition to ensure an early diagnosis. By recognizing the signs and symptoms early, doctors can potentially improve patient outcomes and save lives.

Objectives: We assessed reporting misclassification for 12 critical congenital heart defects (CCHDs) identified through administrative diagnosis codes within a passive surveillance system. We measured the effect of misclassification on prevalence estimation. Lastly, we investigated a sample-based review strategy to estimate surveillance misclassification resulting from administrative diagnosis codes for case detection., Methods: We received 419 reports of CCHDs between 2007 and 2018; 414 were clinically reviewed. We calculated confirmation probabilities to assess misclassification and adjust prevalence estimates. Random samples of reported cases were taken at proportions between 20% and 90% for each condition to assess sample bias. Sampling was repeated 1000 times to measure sample-estimate variability., Results: Misclassification ranged from a low of 19% (n = 4/21) to a high of 84% (n = 21/25). Unconfirmed prevalence rates ranged between one and six cases per 10,000 live births, with some conditions significantly higher than national estimates. However, confirmed rates were either lower or comparable to national estimates., Conclusion: Passive birth defect surveillance programs that rely on administrative diagnosis codes for case identification of CCHDs are subject to misclassification that bias prevalence estimates. We showed that a sample-based review could improve the prevalence estimates of 12 cardiovascular conditions relative to their unconfirmed prevalence rates., (© 2024 Wiley Periodicals LLC.)

Purpose: Psychometric properties and diagnostic performance of the ADOS-2 module 4 were evaluated with participants from an autism-specialized clinic., Methods: The sample had 331 participants with 226 males and 70 females receiving an ASD diagnosis. The evaluation consisted of the following: (1) A replication of the Exploratory Factor Analysis (EFA) reported by Hus, V., & Lord, C. (2014). The Autism Diagnostic Observation Schedule, Module 4: Revised Algorithm and Standardized Severity Scores. Journal of Autism and Developmental Disorders, 44(8), 1996-2012. https://doi.org/10.1007/s10803014-2080-3 .). (2) Identification of ADOS-2 items best predicting clinical diagnosis using Recursive Feature Elimination (RFE) and comparison of these items to previous findings. (3) Receiver Operating Characteristic (ROC) curve analyses of the effects of age and IQ on diagnostic performance. (4) Comparisons of ADOS-2 revised algorithm scores between females and males and their association with ADI-R scores., Results: The EFA item-to-factor allocation of the ADOS-2 revised algorithm was largely reproduced. When comparing the present RFE to previous RFE findings, the item Quality of Social Responses stood out. ROC curve analysis showed outstanding diagnostic performance for adults with IQ above 70 but for females, ADOS-2 revised algorithm scores were lowered, and, contrary to males, did not correlate with ADI-R scores., Conclusion: Reproducing the item-to-factor allocation and finding outstanding agreement with the diagnostic decision for adults with IQ > 70 showcase the strength of the ADOS-2 revised algorithm. Furthermore, by incorporating, into future revisions, the finding of inter-clinic importance of the item Quality of Social Responses, performance might be further enhanced. Lastly, though, that female scores were lowered and did not correlate with ADI-R indicate a weakness in the ADOS-2 when applied to the adult female population., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Knowledge is limited on associations between social disconnectedness (i.e. loneliness and social isolation), health literacy and perceived treatment burden in individuals with cardiovascular disease (CVD). However, understanding these associations may be important for clinical practice., Methods: This study used cross-sectional self-reported data from the 2017 Danish health and morbidity survey entitled 'How are you?', investigating the associations of loneliness and social isolation with low health literacy and high treatment burden in individuals with CVD (n = 2521; mean age = 65.7 years)., Results: Logistic regression analysis showed that loneliness and social isolation were associated with low health literacy in terms of difficulties in 'understanding health information' (loneliness: adjusted odds ratio (AOR) = 1.32, 95% confidence intervals (CI) [1.16, 1.50]; social isolation: AOR = 1.47, 95% CI [1.24, 1.73]) and 'engaging with healthcare providers' (loneliness: AOR = 1.53, 95% CI [1.37, 1.70]; social isolation: AOR = 1.21, 95% CI [1.06, 1.40]) and associated with high treatment burden (loneliness: AOR = 1.49, 95% CI [1.35, 1.65]; social isolation: AOR = 1.20, 95% CI [1.06, 1.37])., Conclusions: Our findings show that loneliness and social isolation coexisted with low health literacy and high treatment burden in individuals with CVD. These findings are critical as socially disconnected individuals experience more health issues. Low health literacy and a high treatment burden may potentially exacerbate these issues., (© 2024. The Author(s).)

Background: When implementing new interventions into clinical practice, it is of great importance to investigate the implementation process to better understand factors promoting and impeding the implementation to stimulate engagement and sustainability of the intervention. It is essential to consider perspectives both from the health professionals delivering the intervention and those receiving the intervention to be open to their suggestions for enhancing the dissemination and implementation of the intervention. The aim of the study was to evaluate adoption, acceptability and appropriateness of a person-centred group intervention (PCGI) from the perspectives of facilitators and participants with mental illness in mental health outpatient services right after delivery., Methods: A qualitative interview study design was used. Interview data from three individual interviews, one group interview with facilitators and 16 individual interviews with participants were analyzed through content analysis., Results: As described in the following three categories, the facilitators and participants found the PCGI overall useful and meaningful to deliver and receive: (1) application of a PCGI in clinical practice, (2) balancing the facilitator role and (3) establishing and maintaining a safe relationship., Conclusion: Facilitators and participants found the form and structure of the PCGI useful and meaningful. Some participants dropped out as they did not feel comfortable in a group setting. The components in the sessions, questions on cards and reflection sheets together with peer-to-peer interactions provided a safe environment. However, facilitation from facilitators requires appropriate skills and qualifications, which must be provided by the hospital together with supervision and the possibility for peer feedback and exchange of experiences., (© 2024 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Aims: Prolonged loneliness and severe stress are increasingly recognised as public health concerns and considered risk factors for mental disorders, somatic illnesses and mortality. Loneliness and perceived stress also often co-occur; however, their longitudinal relation remains unclear. To the best of our knowledge, this is the first study aiming to investigate the longitudinal relation between loneliness and perceived stress independently of cross-sectional associations and time effects., Methods: Designed as a population-based cohort study with repeated measurements, the present study included individuals aged 16-80 years at baseline who participated in the Danish National Health Survey ('How are you?') in 2013 and 2017 ( N = 10,159; response rate = 50%). Structural equation modelling was used to examine associations between loneliness and perceived stress in the total sample and across age groups (i.e., 16-29, 30-64 and 65-80 years)., Results: The models indicated bidirectional relations between loneliness and perceived stress. The standardized cross-lagged path from loneliness to perceived stress (β: 0.12, 95% confidence interval (CI) (0.08, 0.16), p < 0.001) and from perceived stress to loneliness (β: 0.12, 95% CI (0.07, 0.16), p < 0.001) both corresponded to small effect sizes in the total sample. Additionally, the results indicated strong cross-sectional associations, especially among adolescents and young adults (16-29 years), and high temporal stability, especially among the elderly (65-80 years)., Conclusions: Loneliness and perceived stress mutually predict each other over time. The finding of both substantial bidirectional and cross-sectional associations demonstrates an interdependence between loneliness and perceived stress that may be relevant to consider in future interventions., Competing Interests: Conflict of interestThe authors declared no potential conflicts of interest with respect to the research, authorship and publication of this article.

Background: To contribute to the discovery of new microbial strains with metabolic and physiological robustness and develop them into successful chasses, Paracoccus pantotrophus DSM 2944, a Gram-negative bacterium from the phylum Alphaproteobacteria and the family Rhodobacteraceae, was chosen. The strain possesses an innate ability to tolerate high salt concentrations. It utilizes diverse substrates, including cheap and renewable feedstocks, such as C1 and C2 compounds. Also, it can consume short-chain alkanes, predominately found in hydrocarbon-rich environments, making it a potential bioremediation agent. The demonstrated metabolic versatility, coupled with the synthesis of the biodegradable polymer polyhydroxyalkanoate, positions this microbial strain as a noteworthy candidate for advancing the principles of a circular bioeconomy., Results: The study aims to follow the chassis roadmap, as depicted by Calero and Nikel, and de Lorenzo, to transform wild-type P. pantotrophus DSM 2944 into a proficient SynBio (Synthetic Biology) chassis. The initial findings highlight the antibiotic resistance profile of this prospective SynBio chassis. Subsequently, the best origin of replication (ori) was identified as RK2. In contrast, the non-replicative ori R6K was selected for the development of a suicide plasmid necessary for genome integration or gene deletion. Moreover, when assessing the most effective method for gene transfer, it was observed that conjugation had superior efficiency compared to electroporation, while transformation by heat shock was ineffective. Robust host fitness was demonstrated by stable plasmid maintenance, while standardized gene expression using an array of synthetic promoters could be shown. pEMG-based scarless gene deletion was successfully adapted, allowing gene deletion and integration. The successful integration of a gene cassette for terephthalic acid degradation is showcased. The resulting strain can grow on both monomers of polyethylene terephthalate (PET), with an increased growth rate achieved through adaptive laboratory evolution., Conclusion: The chassis roadmap for the development of P. pantotrophus DSM 2944 into a proficient SynBio chassis was implemented. The presented genetic toolkit allows genome editing and therewith the possibility to exploit Paracoccus for a myriad of applications., (© 2024. The Author(s).)

Understanding the emergent electronic structure in twisted atomically thin layers has led to the exciting field of twistronics. However, practical applications of such systems are challenging since the specific angular correlations between the layers must be precisely controlled and the layers have to be single crystalline with uniform atomic ordering. Here, an alternative, simple, and scalable approach is suggested, where nanocrystallinetwo-dimensional (2D) film on 3D substrates yields twisted-interface-dependent properties. Ultrawide-bandgap hexagonal boron nitride (h-BN) thin films are directly grown on high in-plane lattice mismatched wide-bandgap silicon carbide (4H-SiC) substrates to explore the twist-dependent structure-property correlations. Concurrently, nanocrystalline h-BN thin film shows strong non-linear second-harmonic generation and ultra-low cross-plane thermal conductivity at room temperature, which are attributed to the twisted domain edges between van der Waals stacked nanocrystals with random in-plane orientations. First-principles calculations based on time-dependent density functional theory manifest strong even-order optical nonlinearity in twisted h-BN layers. This work unveils that directly deposited 2D nanocrystalline thin film on 3D substrates could provide easily accessible twist-interfaces, therefore enabling a simple and scalable approach to utilize the 2D-twistronics integrated in 3D material devices for next-generation nanotechnology., (© 2023 Wiley-VCH GmbH.)

The mounting evidence that loneliness is a determinant of poor health and well-being underpins the need for effective interventions and community action. 'More Together' (MoTo) is a large-scale, complex, multi-component and multi-level intervention for community change that addresses loneliness among young people and older adults in Silkeborg Municipality, Denmark. The intervention is inspired by the Collective Impact framework, and it is practice driven and rooted in an extensive cross-sector partnership. This article outlines (i) the organization of the cross-sector partnership, (ii) the structure of the intervention programme, (iii) the key components and activities of the programme and, finally, (iv) the intervention setting and target population. MoTo aims to create new ways to develop, implement and evaluate loneliness interventions. Experiences gained from MoTo hold the potential to transform our understanding of loneliness interventions and may inform and guide future interventions., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Up to 25% of the US population harbor Clostridioides difficile in the gut. Following antibiotic disruption of the gut microbiota, C. difficile can act as an opportunistic pathogen and induce potentially lethal infections. Consequently, reducing the colonization of C. difficile in at-risk populations is warranted, prompting us to identify and characterize a probiotic candidate specifically targeting C. difficile colonization. We identified Bacillus velezensis DSM 33864 as a promising strain to reduce C. difficile levels in vitro. We further investigated the effects of B. velezensis DSM 33864 in an assay including human fecal medium and in healthy or clindamycin-treated mouse models of C. difficile colonization. The addition of B. velezensis DSM 33864 to human fecal samples was shown to reduce the colonization of C. difficile in vitro. This was supported in vivo where orally administered B. velezensis DSM 33864 spores reduced C. difficile levels in clindamycin-treated mice. The commensal microbiota composition or post-antibiotic reconstitution was not impacted by B. velezensis DSM 33864 in human fecal samples, short-, or long-term administration in mice. In conclusion, oral administration of B. velezensis DSM 33864 specifically reduced C. difficile colonization in vitro and in vivo without adversely impacting the commensal gut microbiota composition., (© 2023. Springer Nature Limited.)

Boron nitride (BN) is an exceptional material, and among its polymorphs, two-dimensional (2D) hexagonal and three-dimensional (3D) cubic BN (h-BN and c-BN) phases are most common. The phase stability regimes of these BN phases are still under debate, and phase transformations of h-BN/c-BN remain a topic of interest. Here, we investigate the phase stability of 2D/3D h-BN/c-BN nanocomposites and show that the coexistence of two phases can lead to strong nonlinear optical properties and low thermal conductivity at room temperature. Furthermore, spark-plasma sintering of the nanocomposite shows complete phase transformation to 2D h-BN with improved crystalline quality, where 3D c-BN possibly governs the nucleation and growth kinetics. Our demonstration might be insightful in phase engineering of BN polymorph-based nanocomposites with desirable properties for optoelectronics and thermal energy management applications.