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Background: Transanal total mesorectal excision (TaTME), a novel approach for treating low rectal cancer, holds promise. However, concerns exist in certain countries about their oncologic safety due to less-than-optimal outcomes on global studies. This research seeks to evaluate the long-term oncologic outcomes focusing on local recurrence rate and overall survival after TaTME surgery in Germany. Patients and methods: This study analyzed data from patients who underwent elective TaTME surgery between 2014 and 2021 in four certified colorectal cancer centers in Germany. Primary endpoints were 3-year local recurrence rate and local recurrence-free survival (LRFS). Secondary outcomes encompassed overall survival (OS), operative time, completeness of local tumor resection, lymph node resection, and postoperative complications. Results: A total of 378 patients were analyzed (mean age 61.6 years; 272 males, 72%). After a median follow-up period of 2.5 years, 326 patients with UICC-stages I–III and tumor operability included in survival analyses. Local recurrence was observed in 8 individuals, leading to a 3-year cumulative local recurrence rate of 2.2% and a 3-year LRFS rate of 88.1%. The 3-year OS rate stood at 88.9%. Within 30 days after surgery, anastomotic leakage occurred in 19 cases (5%), whereas a presacral abscess was present in 12 patients (3.2%). Conclusion: TaTME proves effective in addressing the anatomical and technical challenges of low rectal surgery and is associated with pleasing short- and long-term results. However, its safe integration into surgical routine necessitates sufficient knowledge and a previously completed training program. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection affects 300 million patients worldwide1,2, in whom virus-specific CD8 T cells by still ill-defined mechanisms lose their function and cannot eliminate HBV-infected hepatocytes3–7. Here we demonstrate that a liver immune rheostat renders virus-specific CD8 T cells refractory to activation and leads to their loss of effector functions. In preclinical models of persistent infection with hepatotropic viruses such as HBV, dysfunctional virus-specific CXCR6+ CD8 T cells accumulated in the liver and, as a characteristic hallmark, showed enhanced transcriptional activity of cAMP-responsive element modulator (CREM) distinct from T cell exhaustion. In patients with chronic hepatitis B, circulating and intrahepatic HBV-specific CXCR6+ CD8 T cells with enhanced CREM expression and transcriptional activity were detected at a frequency of 12–22% of HBV-specific CD8 T cells. Knocking out the inhibitory CREM/ICER isoform in T cells, however, failed to rescue T cell immunity. This indicates that CREM activity was a consequence, rather than the cause, of loss in T cell function, further supported by the observation of enhanced phosphorylation of protein kinase A (PKA) which is upstream of CREM. Indeed, we found that enhanced cAMP–PKA-signalling from increased T cell adenylyl cyclase activity augmented CREM activity and curbed T cell activation and effector function in persistent hepatic infection. Mechanistically, CD8 T cells recognizing their antigen on hepatocytes established close and extensive contact with liver sinusoidal endothelial cells, thereby enhancing adenylyl cyclase–cAMP–PKA signalling in T cells. In these hepatic CD8 T cells, which recognize their antigen on hepatocytes, phosphorylation of key signalling kinases of the T cell receptor signalling pathway was impaired, which rendered them refractory to activation. Thus, close contact with liver sinusoidal endothelial cells curbs the activation and effector function of HBV-specific CD8 T cells that target hepatocytes expressing viral antigens by means of the adenylyl cyclase–cAMP–PKA axis in an immune rheostat-like fashion.A liver-intrinsic mechanism is presented that suppresses effective anti-hepatitis virus B responses in mice and humans by rendering virus-specific CD8 T cells refractory to activation causing loss of effector functions. [ABSTRACT FROM AUTHOR]

Settlement expansion and commercial agriculture affect landscape sustainability and ecosystem service provision. Integrated landscape approaches are promoted to negotiate trade-offs between competing land uses and their reconciliation. Incorporating local perceptions of landscape dynamics as basis for such negotiations is particularly relevant for sub-Saharan Africa, where most people depend on natural ecosystems for livelihoods and well-being. This study applied participatory scenario building and spatially explicit simulation to unravel perceptions of the potential impact of rubber and settlement expansion on the provision of selected ecosystem services in southwestern Ghana under a business-as-usual scenario. We collected data in workshops and expert surveys on locally relevant ecosystem services, their indicator values, and the probable land-use transitions. The data was translated into an assessment matrix and integrated into a spatially explicit modeling platform, allowing visualization and comparison of the impact on ecosystem service provision of land-use scenarios under rubber plantation and settlement expansion. The results show the capacity of current (2020) and future land-use patterns to provide locally relevant ecosystem services, indicating a decline in capacity of ecosystem service provisioning in the future compared to the 2020 land-use patterns, a threat to the benefits humans derive from ecosystems. This highlights urgent need for policies and measures to control the drivers of land-use/land-cover change. Furthermore, the results emphasize the importance of diversifying land-use/land-cover types for sustainable landscape development. The paper contributes new insights into how spatially explicit and semi-quantitative methods can make stakeholder perceptions of landscape dynamics explicit as a basis for implementing integrated landscape approaches. [ABSTRACT FROM AUTHOR]

Angiogenesis is a crucial process in the progression of various pathologies, like solid tumors, wet age-related macular degeneration, and chronic inflammation. Current anti-angiogenic treatments still have major drawbacks like limited efficacy in diseases that also rely on inflammation. Therefore, new anti-angiogenic approaches are sorely needed, and simultaneous inhibition of angiogenesis and inflammation is desirable. Here, we show that 2-desaza-annomontine (C81), a derivative of the plant alkaloid annomontine previously shown to inhibit endothelial inflammation, impedes angiogenesis by inhibiting CDC2-like kinases (CLKs) and WNT/β-catenin signaling. C81 reduced choroidal neovascularization in a laser-induced murine in vivo model, inhibited sprouting from vascular endothelial growth factor A (VEGF-A)-activated murine aortic rings ex vivo, and reduced angiogenesis-related activities of endothelial cells in multiple functional assays. This was largely phenocopied by CLK inhibitors and knockdowns, but not by inhibitors of the other known targets of C81. Mechanistically, CLK inhibition reduced VEGF receptor 2 (VEGFR2) mRNA and protein expression as well as downstream signaling. This was partly caused by a reduction of WNT/β-catenin pathway activity, as activating the pathway induced, while β-catenin knockdown impeded VEGFR2 expression. Surprisingly, alternative splicing of VEGFR2 was not detected. In summary, C81 and other CLK inhibitors could be promising compounds in the treatment of diseases that depend on angiogenesis and inflammation due to their impairment of both processes. [ABSTRACT FROM AUTHOR]

Recent technological advancements allow companies to incorporate increasingly heterogeneous and interrelated features into their products, which heightens the products' complexity. In four experimental studies conducted with two product categories, this article reveals similarities and differences in terms of how the heterogeneity and interrelatedness of product features influence consumer attitudes (i.e., expected product usability and capability) and, in turn, purchase intentions. Moreover, it shows that both neglected dimensions of product complexity affect the corresponding influence of the number of product features but do so in considerably different ways. The findings suggest that companies can foster consumer adoption by deemphasizing a product's feature heterogeneity, thereby avoiding low expected product usability, and by emphasizing its feature interrelatedness, thereby promoting high expected product capability. This article provides insights into how companies can manage the complexity of products during both product design (i.e., before market launch) and product advertising and selling (i.e., after market launch). [ABSTRACT FROM AUTHOR]

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Background: Endometriosis is a chronic, estrogen-dependent, inflammatory condition which affects women of reproductive age physically and psychologically in their everyday life. The most common symptom is chronic lower abdominal pain. Apart from physical pain, endometriosis often also leads to an unfulfilled desire to give birth. In general, these two main aspects alone lead to emotional stress for patients and often initiate depressive symptoms. To what extent endometriosis patients are additionally affected by the COVID pandemic and its effects is to be determined in this study. Methods: Patients who presented at our endometriosis center and met the study criteria were offered participation in the study. A link to an online questionnaire (SoSci-Survey) was sent by email. The online questionnaire evaluated depressive symptoms before and during the pandemic as well as the pain perception and perceived support during the pandemic. The data of 167 fully completed questionnaires were evaluated and analyzed using SPSS. Results: The analysis of the questionnaires revealed a significant association between pain levels and depressive symptomatology in endometriosis patients during the pandemic. Patients with more severe pain showed significantly higher depressive symptoms than patients with little or no pain. During the pandemic, patients showed higher depressive symptoms than before. In addition, it was found that those endometriosis patients who felt left alone with their pain due to the consequences of the COVID pandemic, or who felt they had to endure the pain alone, also had higher depressive symptoms. Conclusion: In summary, it can be observed that endometriosis patients with a high pain burden had significantly higher depressive symptoms during the COVID pandemic. The consequences of the pandemic often led to the feeling of having to cope with the symptoms alone or having to endure pain alone, which in turn increased the depressive symptoms. As treating physicians, we should be aware of these connections and try to counteract them with targeted offers and support. [ABSTRACT FROM AUTHOR]

Due to demographic change and transformations in domestic structures as well as working environments, the need for formal care continues to increase. This process leads to a significantly greater number of care workers that will be needed in the future. Concurrently, the demands on caregivers concerning the amount of care and quality of care are increasing. Socially-assistive robots (SARs) are a promising resource in this regard. At the same time, research that directly addresses the target group of elderly persons with cognitive impairments is underrepresented. This study reports observations regarding the interaction between a SAR and elderly people with cognitive impairments. Seven observational and behavioural measures were conducted during the interaction between residents of a nursing home and the SAR named "James". Twelve participants from two residential homes took part in the study. Data were analysed by using content analysis and interpreted along a technology acceptance model. Verbal comments and observable emotions of the SAR were predominantly positive, only a few participants reacted negatively to the SAR "James". There was also hardly any shyness to touch the robot. The participants made eye contact and responded adequately to the robot's requests. Tasks which were set by the SAR in group settings led to a higher communication between the participants than tasks in single-user settings. The mainly upbeat emotions and interaction with the SAR indicates a positive attitude towards the system. Long-term studies are needed to investigate the sustainability of robot acceptance. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic surgery (LS) is hypothesized to result in milder proinflammatory reactions due to less severe operative trauma, which may contribute to the observed clinical benefits after LS. However, previous systematic reviews and meta-analyses on the impact of LS on immunocompetence are outdated, limited and heterogeneous. Therefore, the humoral response after laparoscopic and open colorectal cancer (CRC) resections was evaluated in a comprehensive systematic review and meta-analysis. Methods: Included were randomized controlled trials (RCTs) measuring parameters of humoral immunity after LS compared to open surgery (OS) in adult patients with CRC of any stage. MEDLINE, Embase, Web of Science (SCI-EXPANDED), Cochrane Library, Google Scholar, ClinicalTrials.gov and ICTRP (World Health Organization) were systematically searched. Risk of bias (RoB) was assessed using the Cochrane RoB2 tool. Weighted inverse variance meta-analysis of mean differences was performed for C-reactive protein (CRP), interleukin (IL)-6, IL-8, tumour necrosis factor (TNF)α and vascular endothelial growth factor (VEGF) using the random-effects method. Methods were prospectively registered in PROSPERO (CRD42021264324). Results: Twenty RCTs with 1131 participants were included. Narrative synthesis and meta-analysis up to 8 days after surgery was performed. Quantitative synthesis found concentrations to be significantly lower after LS at 0–2 h after surgery (IL-8), at 3–9 h (CRP, IL-6, IL-8, TNFα) and at postoperative day 1 (CRP, IL-6, IL-8, VEGF). At 3–9 h, IL-6 was notably lower in the LS group by 86.71 pg/ml (mean difference [MD] − 86.71 pg/ml [− 125.05, − 48.37], p < 0.00001). Combined narratively, 13 studies reported significantly lower concentrations of considered parameters in LS patients, whereas only one study reported lower inflammatory markers (for CRP and IL-6) after OS. Conclusion: The increase in postoperative concentrations of several proinflammatory parameters was significantly less pronounced after LS than after OS in this meta-analysis. Overall, the summarized evidence reinforces the view of a lower induction of inflammation due to LS. [ABSTRACT FROM AUTHOR]

Climate change affects both the natural (ecological) and manmade (social) systems across the continents. In the Central Himalaya, renowned for its diverse altitudes, climates, landforms, biodiversity, ethnicities, cultures, and farming systems, complex interactions occur between social and ecological subsystems. The research employs the socio-ecological systems (SESs) approach to assess vulnerability and devise effective adaptation strategies for climate change in the region. Three SESs were chosen as templates for the vulnerability and adaptation assessment. Primary data was collected using the participatory rural appraisal (PRA) method from 14 villages with these SESs. We adopted an indicator-based approach to assess vulnerability, including components such as exposure, sensitivity, and adaptive capacity, to calculate the socio-ecological vulnerability index (SEVI). Our results showed varying patterns of vulnerability across the SESs. Sixty-eight percent of the surveyed households have “high” to “very high” socio-ecological vulnerability levels in all three SESs. The results revealed that Himalayan Moist Temperate/Irrigated agrarian (agrarian)-populated (low) community (SESB3) has a “very high” level, Himalayan Moist Temperate/Unirrigated agrarian (small)-populated (low) community (SESB6) has a “high” level, and Alpine/Unirrigated agrarian (small)-populated (low) community (SESA6) has a medium socio-ecological vulnerability level. In addition to assessing vulnerability, we examined current and potential adaptation strategies and associated barriers. The findings revealed major adaptation strategies by the households and communities in agriculture, forest, health, information, infrastructure, policy, natural disasters, livelihood, and water. Our research culminates in the development of an SES-based adaptation framework as a major outcome. This framework assists in understanding local needs and identifying gaps in existing policies and institutional arrangements for sustainable development of the Himalaya. Our SES-based vulnerability and adaptation assessment offers a robust methodology applicable to the entire Indian Himalayan Region and other mountain ecosystems. It provides valuable insights for effective adaptation strategies to address climate change. [ABSTRACT FROM AUTHOR]

The cognitive phenomenology debate centers on two questions. (1) What is an apt characterization of the phenomenology of conscious thought? And (2), what role does this phenomenology play? I argue that the answers to the former question bear significantly on the answers to the latter question. In particular, I show that conservatism about cognitive phenomenology is not compatible with the view that phenomenology explains the constitution of conscious thought. I proceed as follows: To begin with, I analyze the phenomenology of our sensory experiences and argue for a weak phenomenal holism (WPH) about sensory phenomenology. Next, I explore how WPH can be integrated into the competing accounts of cognitive phenomenology. I argue that, given WPH, conservatism turns out to reduce phenomenal character to a merely concomitant phenomenon that has no explanatory power when it comes to the constitution of conscious thoughts. In contrast, liberalism is explanatorily more powerful in this respect. Finally, I propose a new version of liberalism that explains how phenomenology constitutes conscious thoughts and fits best with WPH. [ABSTRACT FROM AUTHOR]

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Although marketing activities are vital for new ventures (NVs) to ensure growth and survival, previous research is silent on how to organize them in firms' infancy. The entrepreneurship literature focuses on which marketing activities to perform in NVs but not on how to organize these activities, whereas the marketing literature concentrates on how to organize marketing activities in established firms but not in NVs, which face specific opportunities and challenges in their early stage of development. This article aims to tackle this research gap by examining marketing's role within NVs' organization. Drawing on in-depth interviews with managers, we identify two key organizational dimensions: marketing's dispersion (related to the proliferation and, thus, wide anchoring of marketing responsibilities) and marketing's structuration (related to the manifestation and, thus, deep anchoring of marketing responsibilities). Through a field survey and archival data, we show that marketing's dispersion enhances NV profitability, while marketing's structuration decreases it, and that with increasing marketing influence (i.e., power of marketing actors) in NVs and NV maturity (i.e., age and size), this diametrical pattern of effects becomes less pronounced. Overall, the findings provide novel theoretical and practical insights into the organizational design of marketing in firms' infancy. [ABSTRACT FROM AUTHOR]

Mercury in wood is an important pool of this heavy metal in forest ecosystems because of its relatively high proportion in the biomass compared to other pools. This paper describes the successful application of a modified methodology for stem disk sampling based on wood particles from stem disks from Donawitz (Styria, Austria; pig iron production), from Brixlegg (Tyrol; former copper and silver mining, copper ore processing and copper recycling), and from Gmunden (Upper Austria; cement production). The maximum mercury concentration in the stem disks from Donawitz (Hinterberg: 20.5 ppb, St. Peter: 9.3 ppb) was recorded in the early 1970s. Several maxima were obtained from the stem disks from Brixlegg: the first was in 1813 (149.9 ppb), potentially even earlier, a second (37.6 ppb) in the late nineteenth century until the late 1920s, and a third local maximum in the 1970s (9.1 ppb), followed by a tendency to decline until the present. A stem disk from Gmunden in Upper Austria showed values of mercury concentrations indicating no increases compared to literature about background sites (≤ 3.2 ppb). This method revealed trends in mercury concentrations in tree rings originating from several different mercury emission sources in Austria coinciding with information about industrial history (where available) together with a justifiable effort. We therefore recommend it for further investigations on mercury concentrations in tree rings and their changes over time. [ABSTRACT FROM AUTHOR]

Purpose: Vulvar cancer is the fourth most common malignancy of the female genital tract after endometrial, ovarian, and cervical carcinoma and affects mainly elderly women. In 2020 there were registered more than 17,000 deaths worldwide related to vulvar carcinoma. Data about target-based therapies and predictive biomarkers for vulva carcinomas are rare so far. The metastasis-associated gene MTA1 is a transcriptional repressor with a potential effect on cancer. Expression of MTA1 was found to be significantly enhanced in gynecological malignancies as breast or ovarian cancer tissues with advanced cancer stages and higher FIGO grading, indicating an important role of MTA1 in the progression of those tumor entities. Due to the lack of information around MTA1 and its significance regarding vulvar carcinoma, this study focuses on the expression of MTA1 in vulvar carcinoma and its correlation to clinicopathological characteristics and prognosis. Methods: A total of 157 paraffin-embedded vulvar cancer tissues were immunohistochemically stained and examined for MTA1 expression by using the immunoreactive score. Subsequently, the values were correlated with clinicopathological parameters. Results: MTA1 was found to be expressed in 94% of the patients in the cytoplasm and 91% in the nucleus. Cytoplasmatic expression of MTA1 was significantly increased in non-keratinizing squamous cell carcinoma and in vulvar carcinoma of the condylomatous type, compared to keratinizing squamous cell carcinoma and vulvar carcinoma of the verrucous type. High MTA1 expression in the nucleus was associated with advanced tumor size as well as higher FIGO grading. In addition, p16 negative vulvar carcinomas showed a higher nuclear expression of MTA1 compared to p16 positive vulvar carcinomas. Suprisingly, Kaplan–Meier analysis showed a significantly lower disease-free survival in tumor samples without a nuclear expression of MTA1. Conclusions: MTA1 was identified as a negative prognostic marker for vulvar carcinoma associated with advanced tumor stage and FIGO grading. A possible explanation could be that the antibody used for this study does not bind to a possible mutation in the C terminal region of MTA leading to negative immunohistochemical staining and this can be correlated with early recurrence in patients with vulvar carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: In recent years, incidence of vulvar cancer has been on the rise, whereas therapeutic options are still restricted. Therefore, new prognosticators and therapeutic targets are essential. Chronic inflammation plays an important role in carcinogenesis and COX-2, and its product prostaglandin E2 and its receptors EP1–4 are known to be important mediators in cancer initiation and progression. Methods: EP1 expression in vulvar cancer specimens (n = 129) was investigated via immunohistochemistry and evaluated using the well-established immunoreactive score (IRS). Subsequently, the values were correlated with clinicopathological parameters. Results: Our analysis did not reveal EP1 expression as a negative prognostic factor in overall and disease-free survival. However, in the subgroup of patients with lymph-node metastasis, overall survival was significantly shorter in tumors with high EP1 expression. Moreover, EP1 expression correlated positively with good differentiation of the tumor, but not with p16 status or COX-2 expression. Conclusions: This study shed first light on EP1 expression in vulvar carcinoma. EP1 expression correlated significantly with the grading of the tumor, suggesting that it influences cell differentiation. Further research on EP1 signaling may lead to a deeper understanding of the molecular mechanisms of carcinogenesis. [ABSTRACT FROM AUTHOR]

Variations in the gene encoding filamin-A-interacting protein 1 (FILIP1) were identified to be associated with a combination of neurological and muscular symptoms. While FILIP1 was shown to regulate motility of brain ventricular zone cells, a process important for corticogenesis, the function of the protein in muscle cells has been less well characterized. The expression of FILIP1 in regenerating muscle fibres predicted a role in early muscle differentiation. Here we analysed expression and localization of FILIP1 and its binding partners filamin-C (FLNc) and microtubule plus-end-binding protein EB3 in differentiating cultured myotubes and adult skeletal muscle. Prior to the development of cross-striated myofibrils, FILIP1 is associated with microtubules and colocalizes with EB3. During further myofibril maturation its localization changes, and FILIP1 localizes to myofibrillar Z-discs together with the actin-binding protein FLNc. Forced contractions of myotubes by electrical pulse stimulation (EPS) induce focal disruptions in myofibrils and translocation of both proteins from Z-discs to these lesions, suggesting a role in induction and/or repair of these structures. The immediate proximity of tyrosylated, dynamic microtubules and EB3 to lesions implies that also these play a role in these processes. This implication is supported by the fact that in nocodazole-treated myotubes that lack functional microtubules, the number of lesions induced by EPS is significantly reduced. In summary, we here show that FILIP1 is a cytolinker protein that is associated with both microtubules and actin filaments, and might play a role in the assembly of myofibrils and their stabilization upon mechanical stress to protect them from damage. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess levels of biomarkers associated with inflammation and tissue destruction in peri-implant crevicular fluid (PICF) of implants provided with customized or standard healing abutments during early implant healing. Materials and methods: Thirty implants were placed in 22 patients with partial posterior edentulism. Subsequently, test group implants (n=15) received one-piece titanium abutments that were fabricated using computer-aided design/computer-aided manufacturing (CAD/CAM). Control group implants (n=15) were provided with standard abutments. PICF collection and standardized periapical radiographs were carried out at suture removal one week later, following crown delivery after 3 months and at 6 months. Expression of C-reactive protein (CRP), interferon-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12A, IL-17A, macrophage inflammatory protein (MIP)-1α, matrix metalloproteinase (MMP)-13, osteopontin, osteoactivin, Receptor Activator of NF-κB (RANK), and TGF-β were analyzed using a multiplex ELISA kit. Results: Both groups showed a significant decrease in protein expression of CRP, IL-1β, IL-6, IL-8, MIP-1α, osteopontin, osteoactivin, and TGF-β, while MMP-13 levels increased during the observation period. A rise in OPG and RANK levels was detected among customized abutments. Expression of CRP was higher, whereas IL-1β, IL-1α, and MIP-1α were decreased in control compared to test group implants after 6 months. Marginal bone loss did not depend on abutment modality. Conclusions: Both abutment types showed distinctive temporal expression of inflammatory biomarkers during 6 months following implant placement. Trial registration: ISRCTN98477184, registration date 18/05/2022 Clinical relevance: Customized healing abutments exert similar effects on inflammation during early implant healing compared to standard healing abutments. [ABSTRACT FROM AUTHOR]

Background: The immune peptidome of OPSCC has not previously been studied. Cancer-antigen specific vaccination may improve clinical outcome and efficacy of immune checkpoint inhibitors such as PD1/PD-L1 antibodies. Methods: Mapping of the OPSCC HLA ligandome was performed by mass spectrometry (MS) based analysis of naturally presented HLA ligands isolated from tumour tissue samples (n = 40) using immunoaffinity purification. The cohort included 22 HPV-positive (primarily HPV-16) and 18 HPV-negative samples. A benign reference dataset comprised of the HLA ligandomes of benign haematological and tissue datasets was used to identify tumour-associated antigens. Results: MS analysis led to the identification of naturally HLA-presented peptides in OPSCC tumour tissue. In total, 22,769 peptides from 9485 source proteins were detected on HLA class I. For HLA class II, 15,203 peptides from 4634 source proteins were discovered. By comparative profiling against the benign HLA ligandomic datasets, 29 OPSCC-associated HLA class I ligands covering 11 different HLA allotypes and nine HLA class II ligands were selected to create a peptide warehouse. Conclusion: Tumour-associated peptides are HLA-presented on the cell surfaces of OPSCCs. The established warehouse of OPSCC-associated peptides can be used for downstream immunogenicity testing and peptide-based immunotherapy in (semi)personalised strategies. [ABSTRACT FROM AUTHOR]

Copyright of Die Unfallchirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zeitschrift für Psychodrama und Soziometrie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Recent studies reporting widespread declines in arthropod biomass, abundance and species diversity raised wide concerns in research and conservation. However, repeated arthropod surveys over long periods are rare, even though they are key for assessing the causes of the decline and for developing measures to halt the losses. We repeatedly sampled arthropod fauna in a representative Swiss agricultural landscape over 32 years (1987, 1997, 2019). Sampling included eight study sites in four different semi-natural and agricultural habitat types and different trap types (pitfall, window, yellow bucket) over an annual period of 10 weeks to capture flying and ground dwelling arthropod taxa. In total, we analyzed 58,448 individuals from 1343 different species. Mean arthropod biomass, abundance and species richness per trap was significantly higher in 2019 than in the prior years. Also, species diversity of the study area was highest in 2019. Three main factors likely have contributed to the observed positive or at least stable development. First, the implementation of agri-environmental schemes has improved habitat quality since 1993, 6 years after the first sampling. Second, landscape composition remained stable, and pesticide and fertilizer was constant over the study period. Third, climate warming might have favored the immigration and increase of warm adapted species. Our results support the idea that changes in arthropod communities over time is highly context-dependent and complex. Implications for insect conservation: We conclude that the integration and long-term management of ecological compensation patches into a heterogenous agricultural landscape supports insect conservation and can contribute to stable or even increased arthropod abundance, biomass and diversity. Future studies are needed to clarify interdepending effects between agricultural management and climate change on insect communities. [ABSTRACT FROM AUTHOR]

Transcriptional memory, by which cells respond faster to repeated stimuli, is key for cellular adaptation and organism survival. Chromatin organization has been shown to play a role in the faster response of primed cells. However, the contribution of post-transcriptional regulation is not yet explored. Here we perform a genome-wide screen to identify novel factors modulating transcriptional memory in S. cerevisiae in response to galactose. We find that depletion of the nuclear RNA exosome increases GAL1 expression in primed cells. Our work shows that gene-specific differences in intrinsic nuclear surveillance factor association can enhance both gene induction and repression in primed cells. Finally, we show that primed cells present altered levels of RNA degradation machinery and that both nuclear and cytoplasmic mRNA decay modulate transcriptional memory. Our results demonstrate that mRNA post-transcriptional regulation, and not only transcription regulation, should be considered when investigating gene expression memory. Transcriptional memory is key for cellular adaptation. Here the authors show that differences in mRNA stability and mRNA degradation machinery between naïve and primed cells facilitate faster gene expression response to repeated stimuli. [ABSTRACT FROM AUTHOR]

In attempts to unify the four known fundamental forces in a single quantum-consistent theory, it is suggested that Lorentz symmetry may be broken at the Planck scale. Here we search for Lorentz violation at the low-energy limit by comparing orthogonally oriented atomic orbitals in a Michelson-Morley-type experiment. We apply a robust radiofrequency composite pulse sequence in the 2F7/2 manifold of an Yb+ ion, extending the coherence time from 200 μs to more than 1 s. In this manner, we fully exploit the high intrinsic susceptibility of the 2F7/2 state and take advantage of its exceptionally long lifetime. We match the stability of the previous best Lorentz symmetry test nearly an order of magnitude faster and improve the constraints on the symmetry breaking coefficients to the 10−21 level. These results represent the most stringent test of this type of Lorentz violation. The demonstrated method can be further extended to ion Coulomb crystals. Breaking of Lorentz symmetry is related to the unification of fundamental forces and the extension of the standard model. Here the authors provide updated bounds on the Lorentz violation, by using measurements with trapped Yb+ ion, that represent an improvement over existing results. [ABSTRACT FROM AUTHOR]

This paper proposes a novel approach to the measurement of linguistic diversity. Drawing on the ecological literature, it proposes an adaptation to languages of the classic distinction between "alpha" (intra-setting), "beta" (inter-setting) and "gamma" (system-level) diversity. We begin by discussing some of the general challenges raised by the measurement of diversity. We review received approaches to the measurement of diversity resting on the concepts of richness and evenness, highlighting some limitations that come to the fore when comparing the respective diversity of different settings and systems. In order to overcome some of these limitations, we adapt the concept of "numbers equivalent" to linguistic diversity measurement indices. On this basis, we derive a multi-level approach to diversity measurement. We provide numerical examples to highlight the properties of this model before discussing its application to language policy issues. [ABSTRACT FROM AUTHOR]

Drug-induced injury to the gastrointestinal tract has gained growing significance in recent years, and the list of causative medications keeps expanding. Herein, we present the case of a 45-year-old female with major depressive disorder treated with two serotonin and norepinephrine reuptake inhibitors (venlafaxine and duloxetine). She developed nausea and weight loss. Endoscopic evaluation of the upper and lower gastrointestinal tract rendered grossly normal mucosa in all segments. Histological examination, however, revealed lymphocytic esophagitis, collagenous gastritis, celiac disease-like intraepithelial lymphocytosis of the duodenum, and incomplete collagenous colitis. Gastrointestinal side effects of psychoactive drugs are largely underrecognized. This is the first report of a mixed lymphocytic and collagenous pattern of injury affecting esophagus, stomach, duodenum, and colon triggered by combined treatment with venlafaxine and duloxetine. In patients with unclear symptoms, obtaining biopsies from mucosa that is normal upon endoscopic inspection may render decisive clues for clinical management. [ABSTRACT FROM AUTHOR]

Poverty alleviation is a global challenge that concerns particularly developing countries, and its reduction has been identified as the first Sustainable Development Goals in 2015. Poverty is a multidimensional and place-oriented phenomenon that cannot be determined with monetary and strict indicators. It also is interrelated with many factors, including household livelihood strategies. Therefore, the main goals of this paper were (a) to introduce a local index to measure the multidimensional poverty situation of rural areas of Iran, (b) to introduce a proper index to evaluate the livelihood strategy of rural households (LSI), and (c) to investigate the relationship between poverty and livelihood strategy. This study uses the multidimensional poverty index (MPI) and a fuzzy approach to evaluate household poverty and livelihood strategy. A sample includes about 20 thousand rural households and was used in this regard. The results indicated that the value of MPI is 0.349, and about 45% of rural households are deprived in at least two-thirds of poverty indicators, and 62.5% of them live in deprived households. Education dimension had the highest contribution in MPI, the LSI value was 0.531, which means rural households often have integrated livelihood strategy, and rural households whose livelihood strategies were more dependent on agriculture also faced with higher poverty and deprivation scores. Finally, the elimination of rural poverty requires a smart approach that is both holistic and systematic. [ABSTRACT FROM AUTHOR]

Femtosecond enhancement cavities1 are key to applications including high-sensitivity linear2–4 and nonlinear5,6 gas spectroscopy, as well as efficient nonlinear optical frequency conversion7–10. Yet, to date, the broadest simultaneously enhanced bandwidths amount to <20% of the central optical frequency8,9,11–15. Here, we present an ultrabroadband femtosecond enhancement cavity comprising gold-coated mirrors and a wedged-diamond-plate input coupler, with an average finesse of 55 for optical frequencies below 40 THz and exceeding 40 in the 120–300 THz range. Resonant enhancement of a 50-MHz-repetition-rate offset-free frequency comb spanning 22–40 THz results in a waveform-stable ultrashort circulating pulse with a spectrum supporting a Fourier limit of 1.6 cycles, enabling time-domain electric-field-resolved spectroscopy of molecular samples with temporally separated excitation and molecular response16. The contrast between the two is improved by taking advantage of destructive interference at the input coupler. At an effective interaction length with a gas of up to 81 m, this concept promises parts-per-trillion-level ultrabroadband electric-field-resolved linear and nonlinear spectroscopy of impulsively excited molecular vibrations. An ultrabroadband femtosecond enhancement cavity is developed, using gold-coated mirrors and a wedged-diamond-plate input coupler. Simultaneous enhancement of a 22–40 THz offset-free frequency comb allows cavity-enhanced time-domain spectroscopy of gas mixtures based on electro-optic sampling in the mid-infrared range. [ABSTRACT FROM AUTHOR]

The streptophyte algal class Zygnematophyceae is the closest algal sister lineage to land plants. In nature, Zygnematophyceae can grow in both terrestrial and freshwater habitats and how they do this is an important unanswered question. Here, we studied what happens to the zygnematophyceaen alga Mougeotia sp., which usually occurs in permanent and temporary freshwater bodies, when it is shifted to liquid growth conditions after growth on a solid substrate. Using global differential gene expression profiling, we identified changes in the core metabolism of the organism interlinked with photosynthesis; the latter went hand in hand with measurable impact on the photophysiology as assessed via pulse amplitude modulation (PAM) fluorometry. Our data reveal a pronounced change in the overall physiology of the alga after submergence and pinpoint candidate genes that play a role. These results provide insight into the importance of photophysiological readjustment when filamentous Zygnematophyceae transition between terrestrial and aquatic habitats. [ABSTRACT FROM AUTHOR]

Summary: Survival in cancer is continuously improving due to evolving oncological treatment. Therefore, cardiovascular short-term and long-term side effects gain crucial importance for overall outcome. Cardiotoxicity not only presents as heart failure, but also as treatment-resistant hypertension, acute coronary ischemia with plaque rupture or vasospasm, thromboembolism, arrhythmia, pulmonary hypertension, diastolic dysfunction, acute myocarditis and others. Recent recommendations have proposed baseline cardiac risk assessment and surveillance strategies. Major challenges are the availability of monitoring and imaging resources, including echocardiography with speckle tracking longitudinal strain (GLS), serum biomarkers such as natriuretic peptides (NT-proBNP) and highly sensitive cardiac troponins. This Austrian consensus encompasses cardiotoxicity occurrence in frequent antiproliferative cancer drugs, radiotherapy, immune checkpoint inhibitors and cardiac follow-up considerations in cancer survivors in the context of the Austrian healthcare setting. It is important to optimize cardiovascular risk factors and pre-existing cardiac diseases without delaying oncological treatment. If left ventricular ejection fraction (LVEF) deteriorates during cancer treatment (from >10% to <50%), or myocardial strain decreases (>15% change in GLS), early initiation of cardioprotective therapies (angiotensin-converting enzyme inhibitors, angiotensin or beta receptor blockers) is recommended, and LVEF should be reassessed before discontinuation. Lower LVEF cut-offs were recently shown to be feasible in breast cancer patients to enable optimal anticancer treatment. Interdisciplinary cardio-oncology cooperation is pivotal for optimal management of cancer patients. [ABSTRACT FROM AUTHOR]

The release and accumulation of pesticides in the environment require the development of novel sustainable technologies for their removal. While adsorption is a classical approach, the design of new materials with enhanced adsorption properties could rationalize the remediation routes and decrease potential risks for their non-target organisms, including humans. More importantly, the use of adsorbents and their synthesis should be implemented in a sustainable and environmentally friendly manner. In this contribution, we studied the adsorption of organophosphorus pesticides (OPs) dimethoate, malathion, and chlorpyrifos on viscose fiber–derived activated carbon fibers (ACFs). The most efficient adsorption was found for chlorpyrifos, followed by malathion and dimethoate, while material properties were correlated with OP uptake. These ACFs are extremely efficient for chlorpyrifos adsorption, with experimentally observed adsorption capacitances reaching 240 mg g−1. Detailed analysis suggests that chlorpyrifos is physisorbed on ACF surfaces and that increased surface hydrophilicity reduces the uptake. Studied ACFs have great potential for practical application. They can reduce OPs' concentrations to such levels that no acute neurotoxic effects of the studied OPs in spiked tap water samples are seen, even for starting concentrations up to 104 times higher than the allowed ones. Finally, this study presents possible guidance for developing even more efficient and environmentally friendly adsorbents for chlorpyrifos, the most toxic among studied OPs. [ABSTRACT FROM AUTHOR]

Semi-continuum modelling of unsaturated porous media flow is based on representing the porous medium as a grid of non-infinitesimal blocks that retain the character of a porous medium. This approach is similar to the hybrid/multiscale modelling. Semi-continuum model is able to physically correctly describe diffusion-like flow, finger-like flow, and the transition between them. This article presents the limit of the semi-continuum model as the block size goes to zero. In the limiting process, the retention curve of each block scales with the block size and in the limit becomes a hysteresis operator of the Prandtl-type used in elasto-plasticity models. Mathematical analysis showed that the limit of the semi-continuum model is a hyperbolic-parabolic partial differential equation with a hysteresis operator of Prandl's type. This limit differs from the standard Richards' equation, which is a parabolic equation and is not able to describe finger-like flow. [ABSTRACT FROM AUTHOR]

Human Milk Oligosaccharides (HMOs) are abundant carbohydrates fundamental to infant health and development. Although these oligosaccharides were discovered more than half a century ago, their biosynthesis in the mammary gland remains largely uncharacterized. Here, we use a systems biology framework that integrates glycan and RNA expression data to construct an HMO biosynthetic network and predict glycosyltransferases involved. To accomplish this, we construct models describing the most likely pathways for the synthesis of the oligosaccharides accounting for >95% of the HMO content in human milk. Through our models, we propose candidate genes for elongation, branching, fucosylation, and sialylation of HMOs. Our model aggregation approach recovers 2 of 2 previously known gene-enzyme relations and 2 of 3 empirically confirmed gene-enzyme relations. The top genes we propose for the remaining 5 linkage reactions are consistent with previously published literature. These results provide the molecular basis of HMO biosynthesis necessary to guide progress in HMO research and application with the goal of understanding and improving infant health and development. Human milk oligosaccharides are fundamental to infant health. Here the authors deploy a multi-omics systems biology approach to elucidate their biosynthetic network, including the associated enzymes and likely structures of ambiguous oligosaccharides. [ABSTRACT FROM AUTHOR]

Transdisciplinary landscape ecology research (in which all stakeholders co-develop landscape plans) requires innovations to support communication and consensus building. From the early stage of the discipline's development, landscape ecologists have been collaborating with researchers from neighboring fields (Kienast et al. [9]), embracing frameworks and approaches of interdisciplinarity. Recent trends indicate a convergence towards new research directions within Landscape Ecology that emphasizes sustainability science and research on social-ecological systems (Li et al. [10]; Wu [19]). Concluding remarks Landscape ecology has profoundly transformed landscape research by its inter- and transdisciplinary nature. [Extracted from the article]

Context: Artificial Intelligence (AI) has rapidly developed over the past several decades. Several related AI approaches, such as Machine Learning (ML), have been applied to research on landscape patterns and ecological processes. Objectives: Our goal was to review the methods of AI, particularly ML, used in studies related to landscape ecology and the main topics addressed. We aimed to assess the trend in the number of ML papers and the methods used therein, and provide a synopsis and prospectus of current use and future applications of ML in landscape ecology. Methods: We conducted a systematic literature search and selected 125 papers for review. These were examined and scored according to multiple criteria regarding methods and topic. We applied quantitative statistical methods, including cluster analysis based on titles, abstracts, and keywords and a non-metric multidimensional scaling based on attributes assigned during the review. We used Random Forests machine learning to describe the differences between identified clusters in terms of the topics and methods they included. Results: The most frequent method found was Random Forests, but it is noteworthy to mention the increasing popularity of tools related to Deep Learning. The topics cover both ecologically oriented issues and the landscape-human interface. There has been a rapid increase in ML and AI methods in landscape ecology research, with Deep Learning and complex multi-step pipeline AI methods emerging in the last several years. Conclusions: The rapid increase in the number of ML papers in landscape ecology research, and the range of methods employed in them, suggest explosive growth in application of these methods in landscape ecology. The increase of Deep Learning approaches in the most recent years suggest a major change in analytical paradigms and methodologies that we feel may transform the field and enable analyses of more complex pattern process relationships across vaster data sets than has been possible previously. [ABSTRACT FROM AUTHOR]

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Background: Since 2010, laparoscopic transanal total mesorectal excision (TaTME) has been increasingly used for low and very low rectal cancer. It is supposed to improve visibility and access to the dissection planes in the pelvis. This study reports on short- and long-term outcomes of the first 100 consecutive patients treated with TaTME in a certified German colorectal cancer center. Patients and methods: Data were derived from digital patient files and official cancer registry reports for patients with TaTME tumor surgery between July 2014 and January 2020. The primary outcome was the 3-year local recurrence rate and local recurrence-free survival (LRFS). Secondary endpoints included overall survival (OAS), disease-free survival (DFS), operation time, completeness of local tumor resection, lymph node resection, and postoperative complications. The Kaplan–Meier method was employed for the survival analyses; competing risks were considered in the time-to-event analysis. Results: During the observation period, the average annual operation time decreased from 272 to 178 min. Complete local tumor resection was achieved in 97% of the procedures. Major postoperative complications (Clavien–Dindo 3–4) occurred in 11% of the cases. At a median follow-up time of 2.7 years, three patients had suffered from a local recurrence. Considering competing risks, this corresponds to a 3-year cumulative incidence rate for local recurrence of 2.2% and a 3-year LRFS of 81.9%. 3-year OAS was 82.9%, and 3-year DFS was 75.7%. Conclusion: TaTME is associated with favorable short and long-term outcomes. Since it is technically demanding, structured training programs and more research on the topic are indispensable. [ABSTRACT FROM AUTHOR]