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Immune-mediated diseases are characterized by aberrant immune responses, posing significant challenges to global health. In both inflammatory and autoimmune diseases, dysregulated immune reactions mediated by tissue-residing immune and non-immune cells precipitate chronic inflammation and tissue damage that is amplified by peripheral immune cell extravasation into the tissue. Chemokine receptors are pivotal in orchestrating immune cell migration, yet deciphering the signaling code across cell types, diseases and tissues remains an open challenge. To delineate disease-specific cell-cell communications involved in immune cell migration, we conducted a meta-analysis of publicly available single-cell RNA sequencing (scRNA-seq) data across diverse immune diseases and tissues. Our comprehensive analysis spanned multiple immune disorders affecting major organs: atopic dermatitis and psoriasis (skin), chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis (lung), ulcerative colitis (colon), IgA nephropathy and lupus nephritis (kidney). By interrogating ligand-receptor (L-R) interactions, alterations in cell proportions, and differential gene expression, we unveiled disease-specific and common cell-cell communications involved in chemotaxis and extravasation to shed light on shared immune responses across tissues and diseases. Further, we performed experimental validation of two understudied cell-cell communications. Insights gleaned from this meta-analysis hold promise for the development of targeted therapeutics aimed at modulating immune cell migration to mitigate inflammation and tissue damage. This nuanced understanding of immune cell dynamics at the single-cell resolution opens avenues for precision medicine in immune disease management.

Background and purposeThe aim of this study was to determine the prevalence of patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) meeting high-risk criteria for early relapse after CD19 CAR T-cell therapy (CART) who have disease encompassable in a standard radiation therapy (RT) plan (defined as

Introductionγ-Aminobutyric acid (GABA) type A receptors (GABAARs) are ligand-gated Cl-channels that mediate the bulk of inhibitory neurotransmission in the mature CNS and are targets of many drugs. During cortical development, GABAAR-mediated signals are significantly modulated by changing subunit composition and expression of Cl-transporters as part of developmental processes and early network activity. To date, this developmental evolution has remained understudied, particularly at the level of cortical layer-specific changes. In this study, we characterized the expression of nine major GABAAR subunits and K-Cl transporter 2 (KCC2) in mouse somatosensory cortex from embryonic development to postweaning maturity.MethodsWe evaluated expression of α1-5, β2-3, γ2, and δ GABAAR subunits using immunohistochemistry and Western blot techniques, and expression of KCC2 using immunohistochemistry in cortices from E13.5 to P25 mice.ResultsWe found that embryonic cortex expresses mainly α3, α5, β3, and γ2, while expression of α1, α2, α4, β2, δ, and KCC2 begins at later points in development; however, many patterns of nuanced expression can be found in specific lamina, cortical regions, and cells and structures.DiscussionWhile the general pattern of expression of each subunit and KCC2 is similar to previous studies, we found a number of unique temporal, regional, and laminar patterns that were previously unknown. These findings provide much needed knowledge of the intricate developmental evolution in GABAAR composition and KCC2 expression to accommodate developmental signals that transition to mature neurotransmission.

Abstract Background Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes. Methods The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed between 2000 and 2012 are included in this study. A comprehensive retrospective analysis was performed on the clinicopathological features, treatment approaches, and outcomes of these cases. The establishment of novel prognostic models was based on in-depth examination of baseline parameters, and subsequent validation in an independent cohort of MCL cases. Results In front-line strategies, the use of hematopoietic stem cell transplantation was the most significant parameter affecting outcomes, for both overall survival (OS, p

Single-cell RNA sequencing (scRNA-seq) experiments provide opportunities to peer into complex tissues at single-cell resolution. However, insightful biological interpretation of scRNA-seq data relies upon precise identification of cell types. The ability to identify the origin of a cell quickly and accurately will greatly improve downstream analyses. We present Sargent, a transformation-free, cluster-free, single-cell annotation algorithm for rapidly identifying the cell types of origin based on cell type-specific markers. We demonstrate Sargent's high accuracy by annotating simulated datasets. Further, we compare Sargent performance against expert-annotated scRNA-seq data from human organs including PBMC, heart, kidney, and lung. We demonstrate that Sargent retains both the flexibility and biological interpretability of cluster-based manual annotation. Additionally, the automation eliminates the labor intensive and potentially biased user annotation, producing robust, reproducible, and scalable outputs. • Sargent is a transformation-free, cluster-free, single-cell annotation algorithm for rapidly identifying the cell types of origin based on cell type-specific markers. • Sargent retains both the flexibility and biological interpretability of cluster-based manual annotation. • Automation eliminates the labor intensive and potentially biased user annotation, producing robust, reproducible, and scalable outputs.

The extreme adaptation potential of the generalist herbivore Tetranychus urticae (the two-spotted spider mite) to pesticides as well as diverse host plants has been associated with clade-specific gene expansions in known detoxifying enzyme families, and with extensive and rapid transcriptional responses. However, how this broad transcriptional potential is regulated remains largely unknown. Using a parental/F1 design in which four inbred strains were crossed to a common inbred strain, we assessed the genetic basis and inheritance of gene expression variation in T. urticae. Mirroring known phenotypic variation in the progenitor strains of the inbreds, we confirmed that the inbred strains we created were genetically distinct, varied markedly in pesticide resistance, and also captured variation in host plant fitness as is commonly observed in this species. By examining differences in gene expression between parents and allele-specific expression in F1s, we found that variation in RNA abundance was more often explained in trans as compared to cis, with the former associated with dominance in inheritance. Strikingly, in a gene ontology analysis, detoxification genes of the cytochrome P450 monooxygenase (CYP) family, as well as dioxygenases (DOGs) acquired from horizontal gene transfer from fungi, were specifically enriched at the extremes of trans-driven up- and downregulation. In particular, multiple CYPs and DOGs with broad substrate-specificities for pesticides or plant specialized compounds were exceptionally highly upregulated as a result of trans-regulatory variation, or in some cases synergism of cis and trans, in the most multi-pesticide resistant strains. Collectively, our findings highlight the potential importance of trans-driven expression variation in genes associated with xenobiotic metabolism and host plant use for rapid adaptation in T. urticae, and also suggests modular control of these genes, a regulatory architecture that might ameliorate negative pleiotropic effects.

Villacis-Perez et al. describe the existence of and the mechanisms sustaining a host race of the spider mite Tetranychus urticae, which was previously regarded as a generalist. Here, the authors identify a specialist host race exhibiting reproductive incompatibility with sympatric generalist populations, as well as significant differences in host performance.

Abstract Background Hydroxychloroquine has not been associated with improved survival among hospitalized COVID-19 patients in the majority of observational studies and similarly was not identified as an effective prophylaxis following exposure in a prospective randomized trial. We aimed to explore the role of hydroxychloroquine therapy in mildly symptomatic patients diagnosed in the outpatient setting. Methods We examined the association between outpatient hydroxychloroquine exposure and the subsequent progression of disease among mildly symptomatic non-hospitalized patients with documented SARS-CoV-2 infection. The primary outcome assessed was requirement of hospitalization. Data was obtained from a retrospective review of electronic health records within a New Jersey USA multi-hospital network. We compared outcomes in patients who received hydroxychloroquine with those who did not applying a multivariable logistic model with propensity matching. Results Among 1274 outpatients with documented SARS-CoV-2 infection 7.6% were prescribed hydroxychloroquine. In a 1067 patient propensity matched cohort, 21.6% with outpatient exposure to hydroxychloroquine were hospitalized, and 31.4% without exposure were hospitalized. In the primary multivariable logistic regression analysis with propensity matching there was an association between exposure to hydroxychloroquine and a decreased rate of hospitalization from COVID-19 (OR 0.53; 95% CI, 0.29, 0.95). Sensitivity analyses revealed similar associations. QTc prolongation events occurred in 2% of patients prescribed hydroxychloroquine with no reported arrhythmia events among those with data available. Conclusions In this retrospective observational study of SARS-CoV-2 infected non-hospitalized patients hydroxychloroquine exposure was associated with a decreased rate of subsequent hospitalization. Additional exploration of hydroxychloroquine in this mildly symptomatic outpatient population is warranted.

IntroductionCytogenetic analysis is important for stratifying patients with various neoplasms. We explored the use of targeted next generation sequencing (NGS) in detecting chromosomal structural abnormalities or copy number variations (CNVs) in patients with myeloid neoplasms.MethodsPlasma cell-free DNA (cfDNA) from 2821 myeloid or lymphoid neoplasm patients were collected. cfDNA was sequenced using a 275 gene panel. CNVkit software was used for analyzing and visualizing CNVs. Cytogenetic data from corresponding bone marrow (BM) samples was available on 89 myeloid samples.ResultsOf the 2821 samples, 1539 (54.5%) showed evidence of mutations consistent with the presence of neoplastic clones in circulation. Of these 1539 samples, 906 (59%) showed abnormalities associated with myeloid neoplasms and 633 (41%) with lymphoid neoplasms. Chromosomal structural abnormalities in cfDNA were detected in 146 (16%) myeloid samples and 76 (12%) lymphoid samples. Upon comparison of the myeloid samples with 89 BM patients, NGS testing was able to reliably detect chromosomal gain or loss, except for fusion abnormalities. When cytogenetic abnormalities were classified according to prognostic classes, there was a complete (100%) concordance between cfDNA NGS data and cytogenetic data.ConclusionsThis data shows that liquid biopsy using targeted NGS is reliable in detecting chromosomal structural abnormalities in myeloid neoplasms. In specific circumstances, targeted NGS may be reliable and efficient to provide adequate information without the need for BM biopsy considering broad mutation profiling can be obtained through adequate sequencing within the same test. Overall, this study supports the use of liquid biopsy for early diagnosis and monitoring of patients with myeloid neoplasms.

We establish the existence and uniqueness of weak solutions to the parabolic system with nonstandard growth condition and cross diffusion, $$\displaylines{ \partial_tu-\text{div}a(x,t,\nabla u)) =\text{div}|F|^{p(x,t)-2}F),\cr \partial_tv-\text{div}a(x,t,\nabla v))=\delta\Delta u, }$$ where $\delta\ge0$ and $\partial_tu,~\partial_tv$ denote the partial derivative of u and v with respect to the time variable t, while $\nabla u$ and $\nabla v$ denote the one with respect to the spatial variable x. Moreover, the vector field $a(x,t,\cdot)$ satisfies certain nonstandard p(x,t) growth, monotonicity and coercivity conditions.

K-Cl transporter KCC2 is an important regulator of neuronal development and neuronal function at maturity. Through its canonical transporter role, KCC2 maintains inhibitory responses mediated by γ-aminobutyric acid (GABA) type A receptors. During development, late onset of KCC2 transporter activity defines the period when depolarizing GABAergic signals promote a wealth of developmental processes. In addition to its transporter function, KCC2 directly interacts with a number of proteins to regulate dendritic spine formation, cell survival, synaptic plasticity, neuronal excitability, and other processes. Either overexpression or loss of KCC2 can lead to abnormal circuit formation, seizures, or even perinatal death. GABA has been reported to be especially important for driving migration and development of cortical interneurons (IN), and we hypothesized that properly timed onset of KCC2 expression is vital to this process. To test this hypothesis, we created a mouse with conditional knockout of KCC2 in Dlx5-lineage neurons (Dlx5 KCC2 cKO), which targets INs and other post-mitotic GABAergic neurons in the forebrain starting during embryonic development. While KCC2 was first expressed in the INs of layer 5 cortex, perinatal IN migrations and laminar localization appeared to be unaffected by the loss of KCC2. Nonetheless, the mice had early seizures, failure to thrive, and premature death in the second and third weeks of life. At this age, we found an underlying change in IN distribution, including an excess number of somatostatin neurons in layer 5 and a decrease in parvalbumin-expressing neurons in layer 2/3 and layer 6. Our research suggests that while KCC2 expression may not be entirely necessary for early IN migration, loss of KCC2 causes an imbalance in cortical interneuron subtypes, seizures, and early death. More work will be needed to define the specific cellular basis for these findings, including whether they are due to abnormal circuit formation versus the sequela of defective IN inhibition.

Patients with hematologic malignancies have poor outcomes from COVID infection and are less likely to mount an antibody response after COVID infection. This is a retrospective study of adult lymphoma patients who received the COVID vaccine between 12/1/2020 and 11/30/2021. The primary endpoint was a positive anti-COVID spike protein antibody level following the primary COVID vaccination series. The primary vaccination series was defined as 2 doses of the COVID mRNA vaccines or 1 dose of the COVID adenovirus vaccine. Subgroups were compared using Fisher's exact test, and unadjusted and adjusted logistic regression models were used for univariate and multivariate analyses. A total of 243 patients were included in this study; 72 patients (30%) with indolent lymphomas; 56 patients (23%) with Burkitt's, diffuse large B-cell lymphoma (DLBCL), and primary mediastinal B-cell lymphoma (PMBL) combined; 55 patients (22%) with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL); 44 patients (18%) with Hodgkin and T-cell lymphomas (HL/TCL) combined; 12 patients (5%) with mantle cell lymphoma; and 4 patients (2%) with other lymphoma types. One-hundred fifty-eight patients (65%) developed anti-COVID spike protein antibodies after completing the primary COVID vaccination series. Thirty-eight of 46 (83%) patients who received an additional primary shot and had resultant levels produced anti-COVID spike protein antibodies. When compared to other lymphoma types, patients with CLL/SLL had a numerically lower seroconversion rate of 51% following the primary vaccination series whereas patients with HL/TCL appeared to have a robust antibody response with a seropositivity rate of 77% (p = 0.04). Lymphoma patients are capable of mounting a humoral response to the COVID vaccines. Further studies are required to confirm our findings, including whether T-cell immunity would be of clinical relevance in this patient population.

Patients with hematologic malignancies have poor outcomes from COVID infection and are less likely to mount an antibody response after COVID infection. This is a retrospective study of adult lymphoma patients who received the COVID vaccine between 12/1/2020 and 11/30/2021. The primary endpoint was a positive anti-COVID spike protein antibody level following the primary COVID vaccination series. The primary vaccination series was defined as 2 doses of the COVID mRNA vaccines or 1 dose of the COVID adenovirus vaccine. Subgroups were compared using Fisher’s exact test, and unadjusted and adjusted logistic regression models were used for univariate and multivariate analyses. A total of 243 patients were included in this study; 72 patients (30%) with indolent lymphomas; 56 patients (23%) with Burkitt’s, diffuse large B-cell lymphoma (DLBCL), and primary mediastinal B-cell lymphoma (PMBL) combined; 55 patients (22%) with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL); 44 patients (18%) with Hodgkin and T-cell lymphomas (HL/TCL) combined; 12 patients (5%) with mantle cell lymphoma; and 4 patients (2%) with other lymphoma types. One-hundred fifty-eight patients (65%) developed anti-COVID spike protein antibodies after completing the primary COVID vaccination series. Thirty-eight of 46 (83%) patients who received an additional primary shot and had resultant levels produced anti-COVID spike protein antibodies. When compared to other lymphoma types, patients with CLL/SLL had a numerically lower seroconversion rate of 51% following the primary vaccination series whereas patients with HL/TCL appeared to have a robust antibody response with a seropositivity rate of 77% (p = 0.04). Lymphoma patients are capable of mounting a humoral response to the COVID vaccines. Further studies are required to confirm our findings, including whether T-cell immunity would be of clinical relevance in this patient population.

Maize (Zea mays subsp. mays) yield loss from arthropod herbivory is substantial. While the basis of resistance to major insect herbivores has been comparatively well-studied in maize, less is known about resistance to spider mite herbivores, which are distantly related to insects and feed by a different mechanism. Two spider mites, the generalist Tetranychus urticae, and the grass-specialist Oligonychus pratensis, are notable pests of maize, especially during drought conditions. We assessed resistance (antibiosis) to both mites of 38 highly diverse maize lines, including several previously reported to be resistant to one or the other mite species. We found that line B96, as well as its derivatives B49 and B75, were highly resistant to T. urticae. In contrast, neither these three lines, nor any others included in our study, were notably resistant to the specialist O. pratensis. Quantitative trait locus (QTL) mapping with replicate populations from crosses of B49, B75, and B96 to susceptible B73 identified a QTL in the same genomic interval on chromosome 6 for T. urticae resistance in each of the three resistant lines, and an additional resistance QTL on chromosome 1 was unique to B96. Single-locus genotyping with a marker coincident with the chromosome 6 QTL in crosses of both B49 and B75 to B73 revealed that the respective QTL was large-effect; it explained ∼70% of the variance in resistance, and resistance alleles from B49 and B75 acted recessively as compared to B73. Finally, a genome-wide haplotype analysis using genome sequence data generated for B49, B75, and B96 identified an identical haplotype, likely of initial origin from B96, as the source of T. urticae resistance on chromosome 6 in each of the B49, B75, and B96 lines. Our findings uncover the relationship between intraspecific variation in maize defenses and resistance to its major generalist and specialist spider mite herbivores, and we identified loci for use in breeding programs and for genetic studies of resistance to T. urticae, the most widespread spider mite pest of maize.

Chemical control strategies are driving the evolution of pesticide resistance in pest populations. Understanding the genetic mechanisms of these evolutionary processes is of crucial importance to develop sustainable resistance management strategies. The acaricide pyflubumide is one of the most recently developed mitochondrial complex II inhibitors with a new mode of action that specifically targets spider mite pests. In this study, we characterize the molecular basis of pyflubumide resistance in a highly resistant population of the spider mite Tetranychus urticae. Classical genetic crosses indicated that pyflubumide resistance was incompletely recessive and controlled by more than one gene. To identify resistance loci, we crossed the resistant population to a highly susceptible T. urticae inbred strain and propagated resulting populations with and without pyflubumide exposure for multiple generations in an experimental evolution set-up. High-resolution genetic mapping by a bulked segregant analysis approach led to the identification of three quantitative trait loci (QTL) linked to pyflubumide resistance. Two QTLs were found on the first chromosome and centered on the cytochrome P450 CYP392A16 and a cluster of CYP392E6-8 genes. Comparative transcriptomics revealed a consistent overexpression of CYP392A16 and CYP392E8 in the experimental populations that were selected for pyflubumide resistance. We further corroborated the involvement of CYP392A16 in resistance by in vitro functional expression and metabolism studies. Collectively, these experiments uncovered that CYP392A16 N-demethylates the toxic carboxamide form of pyflubumide to a non-toxic compound. A third QTL coincided with cytochrome P450 reductase (CPR), a vital component of cytochrome P450 metabolism. We show here that the resistant population harbors three gene copies of CPR and that this copy number variation is associated with higher mRNA abundance. Together, we provide evidence for detoxification of pyflubumide by cytochrome P450s that is likely synergized by gene amplification of CPR.

ObjectivesThe development of a prognostic mortality risk model for hospitalized COVID-19 patients may facilitate patient treatment planning, comparisons of therapeutic strategies, and public health preparations.MethodsWe retrospectively reviewed the electronic health records of patients hospitalized within a 13-hospital New Jersey USA network between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2, with follow-up through May 29, 2020. With death or hospital discharge by day 40 as the primary endpoint, we used univariate followed by stepwise multivariate proportional hazard models to develop a risk score on one-half the data set, validated on the remainder, and converted the risk score into a patient-level predictive probability of 40-day mortality based on the combined dataset.ResultsThe study population consisted of 3123 hospitalized COVID-19 patients; median age 63 years; 60% were men; 42% had >3 coexisting conditions. 713 (23%) patients died within 40 days of hospitalization for COVID-19. From 22 potential candidate factors 6 were found to be independent predictors of mortality and were included in the risk score model: age, respiratory rate ≥25/minute upon hospital presentation, oxygenation ConclusionsA risk score using six variables is able to prognosticate mortality within 40-days of hospitalization for COVID-19.Trial registrationClinicaltrials.gov Identifier: NCT04347993.

The discrepancy between the FOPT and CIPT approaches for hadronic tau spectral function moments constitutes the major theoretical uncertainty for strong coupling determinations from tau decay data. We show that the discrepancy can be analytically understood since the Borel representations -- which have been assumed to be identical for both approaches previously -- differ in the presence of IR renormalons. This implies that the OPE condensate corrections are different for both approaches and that the discrepancy may eventually be reconciled. In the talk we explain the difference and some mathematical aspects of the FOPT and CIPT Borel representations and show numerical results.

Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83-1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75-1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57-1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials. Trial Registration: Clinicaltrials.gov Identifier: NCT04347993.

The aim of this work is to make a survey of typical flaws presented by modern anticorrosive coatings commonly employed for inside protection of petrochemicals storage tanks and discuss what can be expected from nondestructive inspection with conventional eddy current technique. In this sense, advantages and limitations of the method are discussed taking into account the characteristics of the coatings. Controlled defects were machined in carbon steel substrates in order to simulate localized corrosion. The detectability of the eddy current technique was evaluated for as-applied insulating coatings (with different thicknesses) in presence and absence of iron oxide inside the simulated corrosion defects. Comparing the results obtained with the original C-Scan maps and after the image processing, the machined defects were successfully detected. In this comparison, it was observed a significant improvement for the false defects elimination using image processing. Keywords: Eddy current testing, Coatings, Corrosion, Underfilm corrosion, Pitting

Myelin abnormalities are increasingly being recognized as an important component of a number of neurologic developmental disorders. The integration of many signaling pathways and cell types are critical for correct myelinogenesis. The PI3-K and mechanistic target of rapamycin (mTOR) pathways have been found to play key roles. mTOR is found within two distinct complexes, mTORC1 and mTORC2. mTORC1 activity has been shown to play a major role during myelination, while the role of mTORC2 is not yet well understood. To determine the role of mTORC2 signaling in myelinogenesis, we generated a mouse lacking the critical mTORC2 component Rictor in oligodendrocyte precursors (OPCs). Targeted deletion of Rictor in these cells decreases and delays the expression of myelin related proteins and reduces the size of cerebral white matter tracts. This is developmentally manifest as a transient reduction in myelinated axon density and g-ratio. OPC cell number is reduced at birth without detectable change in proliferation with proportional reductions in mature oligodendrocyte number at P15. The total number of oligodendrocytes as well as extent of myelination, does improve over time. Adult conditional knock-out (CKO) animals do not demonstrate a behavioral phenotype likely due in part to preserved axonal conduction velocities. These data support and extend prior studies demonstrating an important but transient contribution of mTORC2 signaling to myelin development.

BACKGROUND: Osteoarthrosis is a common cause of low back pain. The diagnosis is clinical and can be confirmed by imaging studies. Pain treatment and confirmation of diagnosis are made by intra-articular injection of corticosteroid and by local anesthetic use, due to clinical improvement. A direct monitoring of the procedure can be done under fluoroscopy, a classic technique, or else by an ultrasound-guided procedure. CASE REPORT: Female patient, 88 years old, 1.68 m and 72 kg, with facet osteoarthrosis at L2-L3, L3-L4 and L4-L5 for two years. On physical examination, she exhibited pain on lateralization and spinal extension. We opted in favor of an ultrasound-guided facet joint block. A midline spinal longitudinal scan was obtained, with identification of the desired joint space at L3-L4. A 25 G needle was inserted into the skin by the echographic off-plane ultrasound technique. 1 mL of contrast was administered, with confirmation by fluoroscopy. After aspiration of the contrast, 1 mL of solution containing 0.25% bupivacaine hydrochloride and 10 mg of methylprednisolone acetate was injected. Injections into L3-L4, L2-L3 and L1-L2 to the right were applied. CONCLUSIONS: The visualization of the facet joint by ultrasound involves minimal risk, besides reduction of radiation. This option is suitable for a large part of the population. However, fluoroscopy and computed tomography remain as monitoring techniques indicated for patients with specific characteristics, such as obesity, severe degenerative diseases and anatomical malformations, in which the ultrasound technique is still in need of further study.

Background: osteoarthrosis is a common cause of low back pain. The diagnosis is clinical and can be confirmed by imaging studies. Pain treatment and confirmation of diagnosis are made by intra-articular injection of corticosteroid and by local anesthetic use, due to clinical improvement. A direct monitoring of the procedure can be done under fluoroscopy, a classic technique, or else by an ultrasound-guided procedure. Case report: female patient, 88 years old, 1.68 m and 72 kg, with facet osteoarthrosis at L2–L3, L3–L4 and L4–L5 for two years. On physical examination, she exhibited pain on lateralization and spinal extension. We opted in favor of an ultrasound-guided facet joint block. A midline spinal longitudinal scan was obtained, with identification of the desired joint space at L3–L4. A 25 G needle was inserted into the skin by the echographic off-plane ultrasound technique. 1 mL of contrast was administered, with confirmation by fluoroscopy. After aspiration of the contrast, 1 mL of solution containing 0.25% bupivacaine hydrochloride and 10 mg of methylprednisolone acetate was injected. Injections into L3–L4, L2–L3 and L1–L2 to the right were applied. Conclusions: the visualization of the facet joint by ultrasound involves minimal risk, besides reduction of radiation. This option is suitable for a large part of the population. However, fluoroscopy and computed tomography remain as monitoring techniques indicated for patients with specific characteristics, such as obesity, severe degenerative diseases and anatomical malformations, in which the ultrasound technique is still in need of further study. Resumo: Justificativa: A osteoartrose facetária é causa frequente de dor lombar. O diagnóstico é clínico e pode ser confirmado por imagem. O tratamento da dor e a confirmação do diagnóstico são feitos pela injeção intra-articular de corticosteroide e anestésico local, por causa da melhoria clínica. A monitoração direta do procedimento pode ser feita por fluoroscopia, técnica clássica, ou guiada por ultrassom. Relato de caso: Paciente do sexo feminino, 88 anos, 1,68 m e 72 kg, com osteoartrose facetária em L2–L3, L3–L4 e L4–L5 havia dois anos. No exame físico, dor à lateralização e à extensão da coluna. Optou-se pelo bloqueio da articulação facetária guiado por ultrassom. Foi feito escaneamento longitudinal na linha média da coluna vertebral e identificado o espaço articular desejado em L3–L4. Uma agulha 25 G foi introduzida na pele pela técnica fora de plano ecográfico. Foi administrado 1 mL de contraste, confirmado com fluoroscopia. Após aspiração do contraste, foi injetado 1 mL de solução contendo cloridrato de bupivacaína 0,25% e 10 mg de acetato de metilprednisolona. Foram feitas injeções nos espaços L3–L4, L2–L3 e L1–L2 à direita. Conclusões: A visualização da articulação facetária pelo ultrassom determina mínimo risco e redução da radiação e é indicada para grande parte da população. Ainda assim a fluoroscopia e a tomografia computadorizada permanecem como monitoração indicada para pacientes com características específicas, como obesidade, doenças degenerativas intensas e malformações anatômicas, nas quais o ultrassom ainda necessita de mais estudos. Keywords: Facet block, Low back pain, Ultrasound, Palavras-chave: Bloqueio facetário, Lombalgia, Ultrassom

Rickettsia is a genus of intracellular bacteria that causes a variety of diseases in humans and other mammals and associates with a diverse group of arthropods. Although Rickettsia appears to be common in ticks, most Rickettsia-tick relationships remain generally uncharacterized. The most intimate of these associations is Rickettsia species phylotype G021, a maternally and transstadially transmitted endosymbiont that resides in 100% of I. pacificus in California. We investigated the effects of this Rickettsia phylotype on I. pacificus reproductive fitness using selective antibiotic treatment. Ciprofloxacin was 10-fold more effective than tetracycline in eliminating Rickettsia from I. pacificus, and quantitative PCR results showed that eggs from the ciprofloxacin-treated ticks contained an average of 0.02 Rickettsia per egg cell as opposed to the average of 0.2 in the tetracycline-treated ticks. Ampicillin did not significantly affect the number of Rickettsia per tick cell in adults or eggs compared to the water-injected control ticks. We found no relationship between tick embryogenesis and rickettsial density in engorged I. pacificus females. Tetracycline treatment significantly delayed oviposition of I. pacificus ticks, but the antibiotic's effect was unlikely related to Rickettsia. We also demonstrated that Rickettsia-free eggs could successfully develop into larvae without any significant decrease in hatching compared to eggs containing Rickettsia. No significant differences in the incubation period, egg hatching rate, and the number of larvae were found between any of the antibiotic-treated groups and the water-injected tick control. We concluded that Rickettsia species phylotype G021 does not have an apparent effect on embryogenesis, oviposition, and egg hatching of I. pacificus.

Abstract We calculate the three-loop Wilson coefficients of all physically relevant dimension-four operators, i.e. G μν a G a , μν $$ {G}_{\mu \nu}^a{G}^{a,\mu \nu} $$ , m i q ¯ j q j $$ {m}_i{\overline{q}}_j{q}_j $$ and m i m j m k 2 $$ {m}_i{m}_j{m}_k^2 $$ , in the short-distance expansion of the time-ordered product of a pair of gauge-singlet vector, axial-vector, scalar and pseudo-scalar currents. The results are given for a general non-Abelian gauge theory with arbitrary (compact semi-simple) gauge group and n f light fermion flavors (quarks) in a common arbitrary representation of the gauge group, which includes QCD as a special case. In particular, we allow for arbitrary flavor contents of each of the currents. For the axial-vector current the included contributions from so-called singlet diagrams are consistent with the one-loop axial anomaly.

Abstract The superposition of causal orders shows promise in various quantum technologies. However, the fragility of quantum systems arising from environmental interactions, leading to dissipative behavior and irreversibility, demands a deeper understanding of the possible instabilities in the coherent control of causal orders. In this work, we employ a collisional model to investigate the impact of an open control system on the generation of interference between two causal orders. We present the environmental instabilities for the switch of two arbitrary quantum operations and examine the influence of environmental temperature on each potential outcome of control post-selection. Additionally, we explore how environmental instabilities affect protocol performance, including switching between mutually unbiased measurement observables and refrigeration powered by causal order superposition, providing insights into broader implications.

Abstract Background Diagnosing multiple sclerosis (MS) is challenging due to diverse symptoms and the absence of specific biomarkers. Concurrent autoimmune diseases (AID) or non-specific antibodies further complicate diagnosis, progression monitoring, and management. Data on AID prevalence in MS patients are sparse. This study aims to identify concurrent AIDs alongside MS. Methods In this retrospective single-center study, we analyzed patient records at our university hospital from 2010 to 2017, focusing on cases suspected of inflammatory demyelinating disease. The 2017 McDonald criteria were applied. Additionally, we measured neurofilament light (NfL) levels from available CSF samples in our biobank. Results We identified a total of 315 patients, of whom 66% were women. In total, 13.7% of all patients had concurrent AID, while 20.3% had isolated antibody findings without AID. The most common AID was autoimmune thyroiditis (8.9%), followed by chronic inflammatory skin diseases (1.6%), arthritis (1%), type 1 diabetes (1%), Sjögren’s syndrome (0.6%), and inflammatory bowel diseases (0.6%). Cardiolipin antibodies were the most frequent isolated antibody finding (8.6%). Our data showed that, from the perspective of the initial demyelinating event, neither comorbid AID nor isolated antibodies significantly influenced relapses or MS progression over a median follow-up of 9 months. Standard CSF parameters and NfL levels were similar between the groups at the time of MS diagnosis. Conclusion Our study shows that AIDs, particularly autoimmune thyroiditis, frequently occur at the onset of MS. The proportion of AIDs commonly treated with immunomodulatory therapy in our cohort was similar to that observed in the general population. Comorbid AID did not affect NfL levels, indicating similar disease activity. Future research should explore new AID emergence during the course of MS, especially considering the increased incidence of rheumatic diseases later in life.

Abstract Background Few studies have longitudinally assessed the determinants of depressive symptoms among persons 80 years and older. The aim of this study was to estimate the determinants of depressive symptoms among persons 80 years and older based on 4-wave national longitudinal data from Thailand. Methods Data from the Health, Aging, and Retirement in Thailand study from 2015, 2017, 2020 and 2022 were utilized. The sample was restricted to community-dwelling persons 80 years and older (analytic sample: n = 2763 observations). For the pooled sample, average age was 85.0 years (range 80–117 years). Established measurements were used to assess depressive symptoms. Linear fixed effects regression was applied to assess the time-variant determinants and outcomes. Results Regressions found that higher functional disability and an increase in the number of chronic conditions worsened depressive symptoms. More favourable self-rated physical health, and higher exercise frequency improved depressive symptoms. In addition, among women higher subjective economic status decreased depressive symptoms. Conclusions This longitudinal study enhances our understanding of the determinants of depressive symptoms among persons 80 years and older. Strategies to delay or decrease functional disability, chronic conditions, increase physical activity, and improve subjective economic status may help in reducing depressive symptoms.

Abstract Background This study aimed to investigate the relationship between migration background and the utilization of preventive healthcare services. Methods Cross-sectional data from wave 5 in the year 2014, with a sample size of 7,684 individuals, were extracted from the nationally representative German Ageing Survey. The survey included community-dwelling individuals aged 40 years and above, with migration background serving as the primary independent variable. The outcomes measured included participation in cancer screenings, flu vaccinations, and routine health check-ups. Multiple logistic regressions were used to examine the association between migration background and preventive healthcare services. Results Regressions showed that the presence of a migration background with personal migration experience (compared with not having a migration background) was associated with a lower likelihood of using preventive healthcare services. More precisely, compared to individuals not having a migration background, individuals with a migration background and personal migration experience had a lower likelihood of routine health check-ups (OR = 0.76, 95% CI: 0.61 to 0.95), flu vaccinations (OR = 0.75, 95% CI: 0.59 to 0.95) and cancer screenings (OR = 0.71, 95% CI: 0.57 to 0.89). In contrast, there was no significant association between the presence of a migration background without personal migration experience (compared with not having a migration background) and the use of preventive healthcare services. Conclusion In conclusion, results showed differences between individuals without migration background and individuals with migration background (and with personal migration experience) in terms of using preventive healthcare services. It may be helpful to specifically address individuals with migration background (and with migration experience) in terms of using preventive healthcare services.

Introduction: The objective of this study was to clarify the frequency of fear of dementia and the factors associated with it. Methods: Data were taken from a nationally representative sample (n = 4,000; average age was 54.9 years, SD: 8.5 years, age ranges from 40 to 70 years, 49.6% of the respondents were women). Similar to prior research, fear of dementia was quantified using a tool ranging from 1 (no fear of dementia) to 4 (severe fear of dementia). Results: In sum, 19.0% reported no fear of dementia, 34.6% reported a little fear of dementia, 33.8% reported some fear of dementia, and 12.7% reported severe fear of dementia. Regressions showed that greater fear of dementia was significantly associated with being female, being younger, poorer self-rated health, the presence of at least one chronic disease, not living in the same household with a partner or not being in a relationship at all, having depressive symptoms and anxiety symptoms. Conclusion: Study findings showed that fear of dementia is particularly associated with health-related factors, age and gender. Lifestyle factors and other socioeconomic factors were only occasionally significant. Future research should explore the reasons for such a higher frequency of people’s fear of dementia. It would also be interesting to find out new factors associated with the fear of dementia. Furthermore, further research could focus on cross-country comparisons and could stratify the results by important groups, e.g., by sex or education, but also cultural and ethnic aspects.

Water covers most of the Earth’s surface and is nowhere near a good ecological or recreational state in many areas of the world. Moreover, only a small fraction of the water is potable. As climate change-induced extreme weather events become ever more prevalent, more and more issues arise, such as worsening water quality problems. Therefore, protecting invaluable and useable drinking water is critical. Environmental agencies must continuously check water sources to determine whether they are in a good or healthy state regarding pollutant levels and ecological status. The currently available tools are better suited for stationary laboratory use, and domain specialists lack suitable tools for on-site visualisation and interactive exploration of environmental data. Meanwhile, data collection for laboratory analysis requires substantial time and significant effort. We, therefore, developed an augmented reality system with a Microsoft HoloLens 2 device to explore the visualisation of water quality and status in situ. The developed prototype visualises geo-referenced sensor measurements incorporated into the perspective of the surroundings. Any users interested in water bodies’ conditions can quickly examine and retrieve an overview of water body status using augmented reality and then take necessary steps to address the current situation.

Abstract Background/Aims Our current study aimed to investigate the determinants of dementia among the oldest old using longitudinal data from a representative sample covering both community-dwelling and institutionalized individuals. Methods/Design Longitudinal representative data were taken from the “Survey on quality of life and subjective well-being of the very old in North Rhine-Westphalia (NRW80+)” that surveyed community-dwelling and institutionalized individuals aged 80 years and above (n = 1,296 observations in the analytic sample), living in North Rhine-Westphalia (most populous state of Germany). The established DemTect was used to measure cognitive impairment (i.e., probable dementia). A logistic random effects model was used to examine the determinants of probable dementia. Results The mean age was 86.3 years (SD: 4.2 years). Multiple logistic regressions revealed that a higher likelihood of probable dementia was positively associated with lower education (e.g., low education compared to medium education: OR: 3.31 [95% CI: 1.10–9.98]), a smaller network size (OR: 0.87 [95% CI: 0.79–0.96]), lower health literacy (OR: 0.29 [95% CI: 0.14–0.60]), and higher functional impairment (OR: 13.45 [3.86–46.92]), whereas it was not significantly associated with sex, age, marital status, loneliness, and depressive symptoms in the total sample. Regressions stratified by sex were also reported. Discussion Our study identified factors associated with dementia among the oldest old. This study extends current knowledge by using data from the oldest old; and by presenting findings based on longitudinal, representative data (also including individuals residing in institutionalized settings). Conclusions Efforts to increase, among other things, formal education, network size, and health literacy may be fruitful in postponing dementia, particularly among older women. Developing health literacy programs, for example, may be beneficial to reduce the burden associated with dementia.

Abstract Background Preoperative evaluation of axillary lymph node status is crucial for the selection of both systemic and surgical treatment in early breast cancer. This study assessed the particular role of additional shear wave elastography (SWE) in axillary staging in patients undergoing initial breast cancer diagnostics. Methods One hundred patients undergoing axillary lymph node biopsy due to a sonographically suspicious axillary lymph node were prospectively evaluated with SWE using virtual touch tissue imaging quantification (VTIQ). Mean values of tissue stiffness for axillary tissue and lymph node tissue were measured prior to core-cut biopsy of the lymph node. All lymph nodes were clip-marked during the biopsy. Cut-off values to differentiate between malignant and benign lymph nodes were defined using Youden’s index. Results Lymph nodes with evidence of malignant tumor cells in the final pathological examination showed a significantly higher velocity as measured by SWE, with a mean velocity of 3.48 ± 1.58 m/s compared to 2.33 ± 0.62 m/s of benign lymph nodes (p

Abstract Background The aim of this study was to clarify the link between oral health-related quality of life (independent variable) and loneliness (outcome) among the general adult population (also stratified by sex). Methods Data were taken from a quota-based survey of the German general adult population (representative in terms of state, sex and age group), with n = 5,000 individuals (mean age was 46.9 years, SD: 15.3 years, ranging from 18 to 74 years). Oral health-related quality of life was quantified using the OHIP-G5. Loneliness was quantified using the De Jong Gierveld tool. Multiple linear regressions were conducted. Results After adjusting for several covariates, multiple linear regressions revealed that poor oral health-related quality of life is associated with higher loneliness levels in the total sample (β = 0.12, p

Abstract Apis mellifera, crucial pollinators for both native and cultivated plants, also yield various products such as honey, wax, royal jelly, and propolis, extensively utilized in the food, pharmaceuticals, and cosmetics industries. Nosema ceranae, a prevalent microsporidian worldwide, stands as a significant pathogen for A. mellifera, showing resistance to conventional antibiotics. Consequently, the exploration of novel compounds for N. ceranae control becomes imperative. Dithiocarbimate derivatives emerge as promising antifungal candidates under evaluation for combating various pathogens, particularly those affecting plants. This study assessed the toxicity profile of six dithiocarbimate derivatives on A. mellifera worker survival and N. ceranae pathogen. Among these, four compounds exhibited minimal bee mortality and proceeded to further evaluation against N. ceranae. In vitro assays demonstrated their inhibitory effects on spore germination. Remarkably, the most potent compound suppressed N. ceranae spores by 62% at a concentration of 20 µmol L−1 in vivo. Thus, these dithiocarbimate derivatives represent promising new antifungal agents for combatting nosemosis in honey bee populations.

Abstract In recent years, the diagnosis of gliomas has become increasingly complex. Analysis of glioma histopathology images using artificial intelligence (AI) offers new opportunities to support diagnosis and outcome prediction. To give an overview of the current state of research, this review examines 83 publicly available research studies that have proposed AI-based methods for whole-slide histopathology images of human gliomas, covering the diagnostic tasks of subtyping (23/83), grading (27/83), molecular marker prediction (20/83), and survival prediction (29/83). All studies were reviewed with regard to methodological aspects as well as clinical applicability. It was found that the focus of current research is the assessment of hematoxylin and eosin-stained tissue sections of adult-type diffuse gliomas. The majority of studies (52/83) are based on the publicly available glioblastoma and low-grade glioma datasets from The Cancer Genome Atlas (TCGA) and only a few studies employed other datasets in isolation (16/83) or in addition to the TCGA datasets (15/83). Current approaches mostly rely on convolutional neural networks (63/83) for analyzing tissue at 20x magnification (35/83). A new field of research is the integration of clinical data, omics data, or magnetic resonance imaging (29/83). So far, AI-based methods have achieved promising results, but are not yet used in real clinical settings. Future work should focus on the independent validation of methods on larger, multi-site datasets with high-quality and up-to-date clinical and molecular pathology annotations to demonstrate routine applicability.

Polymer cubosomes (PCs) are 3D porous microparticles with high surface area that have great potential for applications that require a large interfacial area including catalysis, drug delivery, and energy storage. Most reported PCs are based on chemically inert block copolymers (BCPs) with limited intrinsic functionality, which is why they have been mainly used as templating material. Herein, the synthesis, self‐assembly, and loading of poly(4‐vinylpyridine) (P4VP)‐based PCs are reported. The pyridinic moieties are located inside the PC wall and are well‐known functional groups for coordination, cross‐linking, and pH response, which is demonstrated on platinum coordination and pH‐dependent dye release.

Over the past decade, artificial intelligence (AI) methods in pathology have advanced substantially. However, integration into routine clinical practice has been slow due to numerous challenges, including technical and regulatory hurdles in translating research results into clinical diagnostic products and the lack of standardized interfaces.The open and vendor-neutral EMPAIA initiative addresses these challenges. Here, we provide an overview of EMPAIA's achievements and lessons learned. EMPAIA integrates various stakeholders of the pathology AI ecosystem, i.e., pathologists, computer scientists, and industry. In close collaboration, we developed technical interoperability standards, recommendations for AI testing and product development, and explainability methods. We implemented the modular and open-source EMPAIA Platform and successfully integrated 14 AI-based image analysis apps from eight different vendors, demonstrating how different apps can use a single standardized interface. We prioritized requirements and evaluated the use of AI in real clinical settings with 14 different pathology laboratories in Europe and Asia. In addition to technical developments, we created a forum for all stakeholders to share information and experiences on digital pathology and AI. Commercial, clinical, and academic stakeholders can now adopt EMPAIA's common open-source interfaces, providing a unique opportunity for large-scale standardization and streamlining of processes.Further efforts are needed to effectively and broadly establish AI assistance in routine laboratory use. To this end, a sustainable infrastructure, the non-profit association EMPAIA International, has been established to continue standardization and support broad implementation and advocacy for an AI-assisted digital pathology future.

ABSTRACT The Pontal Island, located in the Parque Natural Municipal de Niterói, stands out as a vital remnant of the Atlantic Forest in Rio de Janeiro. With ecosystems including forest, rocky outcrops, restinga, and mangroves, the island is a biodiversity treasure. This study aimed to conduct a monthly floristic survey from September 2021 to August 2022. The study found 194 species, divided into four plant communities, with Fabaceae, Euphorbiaceae, and Myrtaceae being the most representative families. Five species are endemic, ten are threatened, and twelve are new records for Niterói.

Considering the general view that unconventional immune effectors play a major role in antitumor immunity, we recently postulated that the distinct new innate CD8 T-cell pool (co-expressing the transcription factor Eomesodermin and innate markers such as KIR/NKG2A) may counteract tumor cells, and thereby be potential target for cancer therapy. Here, to test this assumption, we used successfully targeted anti-leukemic therapy discontinuation (TFR) in chronic myeloid leukemia (CML). Numerical and functional status of innate CD8 T-cells, iNKT cells and γδ T-cells, in comparison with NK cells, was compared longitudinally between non-relapsed patients (i.e., with > 12 months TFR) and relapsed patients (i.e., who experienced molecular recurrence during the first 12 months after TKI cessation) in a prospective pilot cohort (n=32), starting from treatment discontinuation (D0). Perforin, a key cytotoxic immune player, was expressed in a significantly higher proportion of both innate CD8 T-cell and NK-cell subsets in non-relapsed patients, compared with relapsed patients at D0. In parallel, we assessed the expression of PD-1, an exhaustion marker used as target in cancer therapy. For all T-cell subsets, surface-expression level of PD-1 decreased in non-relapsed patients compared with relapsed patients at D0. This was particularly the case when considering iNKT cells for which surface-expression level of PD-1 even decreased relative to healthy control subjects. Lastly, we found a negative correlation between the proportion of innate CD8 T-cells expressing PD-1 and those expressing perforin in non-relapsed patients at D0. The fact that this was not the case in conventional CD8 T-cells is compatible with a reprogrammed effector profile preferentially targeting innate CD8 T-cells in non-relapsed patients. All in all, our results highlight NK cells and innate CD8 T-cells harboring cytotoxic content, as well as global downregulation of PD-1-expression on effector T-cells, as potential predictive functional signatures for successful TFR in CML. Considering innate CD8 T-cells, further investigations are needed to determine whether their possible contributory role in cancer surveillance in CML could be extended to other cancers, and also whether their targeting by immune cheek-point inhibitors could enhance their anti-tumoral functions.

Abstract Background The inclusion of biomarkers could improve diagnostic accuracy of attention-deficit/hyperactivity disorder (ADHD). One potential biomarker is the ADHD polygenic score (PGS), a measure of genetic liability for ADHD. This study aimed to investigate if the ADHD PGS can provide additional information alongside ADHD rating scales and examination of family history of ADHD to distinguish between ADHD cases and controls. Methods Polygenic scores were calculated for 576 adults with ADHD and 530 ethnically matched controls. ADHD PGS was used alongside scores from the Wender-Utah Rating Scale (WURS) and the Adult ADHD Self-Report Scale (ASRS) as predictors of ADHD diagnosis in a set of nested logistic regression models. These models were compared by likelihood ratio (LR) tests, Akaike information criterion corrected for small samples (AICc), and Lee R². These analyses were repeated with family history of ADHD as a covariate in all models. Results The ADHD PGS increased the variance explained of the ASRS by 0.58% points (pp) (R2 ASRS = 61.11%, R2 ASRS + PGS=61.69%), the WURS by 0.61pp (R2 WURS = 77.33%, R2 WURS + PGS= 77.94%), of ASRS and WURS together by 0.57pp (R2 ASRS + WURS=80.84%, R2 ASRS + WURS+PGS=81.40%), and of self-reported family history by 1.40pp (R2 family = 28.06%, R2 family + PGS=29.46%). These increases were statistically significant, as measured by LR tests and AICc. Conclusion We found that the ADHD PGS contributed additional information to common diagnostic aids. However, the increase in variance explained was small, suggesting that the ADHD PGS is currently not a clinically useful diagnostic aid. Future studies should examine the utility of ADHD PGS in ADHD prediction alongside non-genetic risk factors, and the diagnostic utility of the ADHD PGS should be evaluated as more genetic data is accumulated and computational tools are further refined.

Abstract Background In light of the existing knowledge gap in this research area (particularly based on representative samples and research conducted during the pandemic), the objective of this study was to explore the association between perceived ageism and psychosocial outcomes (i.e., in terms of life satisfaction, loneliness, social isolation, aging satisfaction and depressive symptoms) among middle-aged and older adults during the COVID-19 pandemic based on nationally representative data. Methods We used data from the nationally representative German Ageing Survey, which covers community-dwelling middle-aged and older individuals aged 40 years or over. Specifically, wave 7 of the German Ageing Survey (conducted from November 2020 to March 2021) was analyzed, consisting of a sample of 4,167 individuals with an average age of 68.7 years (SD: 10.1 years; ranging from 46 to 98 years). Established instruments were employed to measure psychosocial outcomes. Results Regressions showed that the presence of perceived ageism was significantly associated with unfavorable psychometric outcomes (i.e., higher loneliness: β = 0.29, p

Integrated geo- and environmental monitoring in mining represents a high-dimensional challenge (location, altitude/depth, time and sensors). This is challenging for experts but poses great problems for a multitude of participants and stakeholders in building up a complete process understanding. The Epe research cooperation aims to elucidate the ground movement at the Epe cavern storage facility with a public participation process. The research cooperation was founded by the city of Gronau, the citizens’ initiative cavern field Epe, the company EFTAS, Münster, and the Research Center of Post-Mining at the Technische Hochschule Georg Agricola, Bochum. This research cooperation is the first in Germany to involve direct collaboration between science and the public. In the cavern field, which has been in operation since the 1970s, brine is extracted, and at the same time natural gas, crude oil and helium, as well as hydrogen in the future, are stored in the subsurface. The technical focus of this work was the development of a high-resolution spatiotemporal analysis of ground movements. The area is monitored annually by the mining company’s mine surveyor. The complexity of the monitoring issue lies in the fact that the western part is a bog area and a former bog area. Furthermore, the soils in the eastern part are very humus-rich and show strong fluctuations in the groundwater and therefore complex hydraulic conditions. At the same time, there are few fixed scatterers or prominent points in the area that allow high-resolution spatiotemporal monitoring using simple radar interferometry methods. Therefore, the SBAS method (Small Baseline Subset), which is based on an aerial method, was used to analyze the radar interferometric datasets. Using an SBAS analysis, it was possible to evaluate a time series of 760 scenes over the period from 2015 to 2023. The results were integrated with the mine survey maps on the ground movement and other open geodata on the surface, the soil layers and the overburden. The results show complex forms of ground movement. The main influence is that of mining. Nevertheless, the influence of organic soils with drying out due to drought years and uplift in wet years is great. Thus, in dry years, ground subsidence accelerates, and in wet years, ground subsidence not only slows down but in some cases also causes uplift. This complexity of ground movements and the necessary understanding of the processes involved has been communicated to the interested public at several public information events as part of the research cooperation. In this way, an understanding of the mining process was built up, and transparency was created in the subsurface use, also as a part of the energy transition. In technical terms, the research cooperation also provides a workflow for developing the annual mine survey maps into an integrated geo- and environmental monitoring system with the development of a transparent participatory geomonitoring process to provide resilience management to a mining location.

Abstract Background Musculoskeletal conditions are a leading contributor to disability worldwide. The treatment of these conditions accounts for 7% of health care costs in Germany and is often provided by physiotherapists. Yet, an overview of the cost-effectiveness of treatments for musculoskeletal conditions offered by physiotherapists is missing. This review aims to provide an overview of full economic evaluations of interventions for musculoskeletal conditions offered by physiotherapists. Methods We systematically searched for publications in Medline, EconLit, and NHS-EED. Title and abstracts, followed by full texts were screened independently by two authors. We included trial-based full economic evaluations of physiotherapeutic interventions for patients with musculoskeletal conditions and allowed any control group. We extracted participants' information, the setting, the intervention, and details on the economic analyses. We evaluated the quality of the included articles with the Consensus on Health Economic Criteria checklist. Results We identified 5141 eligible publications and included 83 articles. The articles were based on 78 clinical trials. They addressed conditions of the spine (n = 39), the upper limb (n = 8), the lower limb (n = 30), and some other conditions (n = 6). The most investigated conditions were low back pain (n = 25) and knee and hip osteoarthritis (n = 16). The articles involved 69 comparisons between physiotherapeutic interventions (in which we defined primary interventions) and 81 comparisons in which only one intervention was offered by a physiotherapist. Physiotherapeutic interventions compared to those provided by other health professionals were cheaper and more effective in 43% (18/42) of the comparisons. Ten percent (4/42) of the interventions were dominated. The overall quality of the articles was high. However, the description of delivered interventions varied widely and often lacked details. This limited fair treatment comparisons. Conclusions High-quality evidence was found for physiotherapeutic interventions to be cost-effective, but the result depends on the patient group, intervention, and control arm. Treatments of knee and back conditions were primarily investigated, highlighting a need for physiotherapeutic cost-effectiveness analyses of less often investigated joints and conditions. The documentation of provided interventions needs improvement to enable clinicians and stakeholders to fairly compare interventions and ultimately adopt cost-effective treatments.

Abstract Laser interferometry enables to remotely measure microscopical length changes of deployed telecommunication cables originating from earthquakes. Long reach and compatibility with data transmission make it attractive for the exploration of both remote regions and highly-populated areas where optical networks are pervasive. However, interpretation of its response still suffers from a limited number of available datasets. We systematically analyze 1.5 years of acquisitions on a land-based telecommunication cable in comparison to co-located seismometers, with successful detection of events in a broad magnitude range, including very weak ones. We determine relations between a cable’s detection probability and the events magnitude and distance, introducing spectral analysis of fiber data as a tool to investigate earthquake dynamics. Our results reveal that quantitative analysis is possible, confirming applicability of this technique both for the global monitoring of our planet and the daily seismicity monitoring of populated areas, in perspective exploitable for civilian protection.

Intraocular drug delivery is a promising approach for treatment of ocular diseases. Chemotherapeutic drugs used in retinoblastoma (RB) treatment often lead to side effects and drug resistances. Therefore, new adjuvant therapies are needed to treat chemoresistant RBs. Biocompatible gold nanoparticles (GNPs) have unique antiangiogenic properties and can inhibit cancer progression. The combination of gold and low‐molecular‐weight hyaluronan (HA) enhances the stability of GNPs and promotes the distribution across ocular barriers. Attached to HA‐GNPs, the atrial natriuretic peptide (ANP), which diminishes neovascularization in the eye, is a promising new therapeutic agent for RB treatment. In the study presented, we established ANP‐coupled HA‐GNPs and investigated their effect on the tumor formation potential of chemoresistant RB cells in an in ovo chicken chorioallantoic membrane model and an orthotopic in vivo RB rat eye model. Treatment of etoposide‐resistant RB cells with ANP‐HA‐GNPs in ovo resulted in significantly reduced tumor growth and angiogenesis compared with controls. The antitumorigenic effect could be verified in the rat eye model, including a noninvasive application form via eye drops. Our data suggest that ANP‐HA‐GNPs represent a new minimally invasive, adjuvant treatment option for RB.

Objective: Food insecurity (FI) is a critical social determinant of poor psychosocial health. While data on the specific roles of sex and age in the FI-loneliness link among older adults are limited, the underlying mechanisms are largely unknown. This study examines the age-sex-specific associations of FI with loneliness among older adults in Ghana and quantifies the extent to which psychosomatic factors mediate the association. Methods: We analyzed cross-sectional data from the Aging, Health, Psychological, and Health-seeking Behavior Study in Ghana. The past 30-day FI was assessed using items on hunger and breakfast skipping frequency due to a lack of resources. We assessed loneliness severity with the University of California, Los Angeles 3-item Loneliness Scale. Multivariable OLS regressions and bootstrapping mediation analysis using the Hayes PROCESS macro plug-in were used to evaluate the associations. Results: We included 1,201 individuals aged ≥50 years (mean = 62.9 [SD = 11.9]; women = 63.3%). The prevalence of loneliness was 17.7%. The prevalence of moderate and severe FI was 44.0% and 8.5%, respectively. In the adjusted model, greater FI was significantly associated with loneliness severity (B = .22, SE = .029, p

Large tropical trees are rightly perceived as supporting a plethora of organisms. However, baseline data about the variety of taxa coexisting on single large tropical trees are lacking and prevent a full understanding of both the magnitude of biodiversity and the complexity of interactions among organisms in tropical rainforests. The two main aims of the research program “Life on Trees” (LOT) are (1) to establish baseline knowledge on the number of eukaryote species supported/hosted by the above-ground part of a single tropical tree and (2) to understand how these communities of organisms are assembled and distributed on or inside the tree. To achieve the first goal, we integrated a set of 36 methods for comprehensively sampling eukaryotes (plants, fungi, animals, protists) present on a tropical tree. The resulting LOT protocol was conceived and implemented during projects in the Andean Amazon region and is proposed here as a guideline for future projects of a similar nature. To address the second objective, we evaluated the microclimatic differences between tree zones and tested state-of-the-art terrestrial laser scanning (TLS) and positioning technologies incorporating satellite and fixed base station signals (dGNSS). A marked variation in temperature and relative humidity was detected along a 6-zones Johansson scheme, a tree structure subdivision system commonly used to study the stratification of epiphytic plants. Samples were collected from these six zones, including three along the trunk and three in the canopy. To better understand how different tree components (e.g., bark, leaves, fruits, flowers, dead wood) contribute to overall tree biodiversity, we categorized observations into communities based on Johansson zones and microhabitats. TLS was an essential aid in understanding the complex tree architecture. By contrast, the accuracy of positioning samples in the tree with dGNSS was low. Comprehensively sampling the biota of individual trees offers an alternative to assessing the biodiversity of fewer groups of organisms at the forest scale. Large old tropical trees provide a wealth of microhabitats that encompass a wide range of ecological conditions, thereby capturing a broad spectrum of biodiversity.

Resumo: O presente artigo tem como principal objetivo estudar as medidas adotadas pelas organizações para mitigar os impactos decorrentes de um incidente de segurança envolvendo dados pessoais, especialmente sob a ótica da Lei Geral de Proteção de Dados (LGPD). Para isso, serão avaliados os aspectos relacionados às orientações, funções, papéis e responsabilidades a serem observadas na gestão interna dos incidentes, bem como o gerenciamento adequado por meio dos procedimentos estabelecidos, que são parte fundamental para a mitigação dos potenciais impactos enfrentados tanto pelos titulares dos dados afetados quanto pela própria organização. O objetivo é discorrer, com base em situações reais, sobre as atividades de gestão para auxiliar na prevenção de incidentes futuros, além de compreender como preparar a organização de forma antecipada e contínua para tratá-los e responder conforme exigido pela legislação aplicável, de modo a garantir a segurança e privacidade dos dados, promovendo a confiança dos clientes e a reputação da empresa. Palavras-chave: incidente; riscos; segurança; privacidade; gerenciamento.

BackgroundThe hepatitis E virus (HEV) can cause acute viral hepatitis with or without neurological manifestations, and occasionally progresses to chronic infection in immunocompromised individuals. The management of chronic HEV infection in cancer patients may be challenging due to the complex immunological constellation. Furthermore, the diagnostic workflow and the impact on quality of life of neurological HEV manifestations in immunocompromised patients have not been sufficiently delineated previously.Case descriptionA 61-year-old male with systemically treated chronic lymphocytic leukemia (CLL) experienced a slowly progressive atrophy of the spinal cord due to a chronic HEV infection. Despite continuous antiviral treatment with ribavirin, the patient’s neurological condition continued to deteriorate, particularly following subsequent attempts to treat CLL. Treatment with obinutuzumab resulted in acute bowel and urinary retention and a further deterioration of motor skills, prompting the discontinuation of obinutuzumab. The patient’s neurological status improved after the administration of intravenous immunoglobulins.ConclusionThis case study provides a comprehensive long-term follow-up of a cancer patient with chronic HEV infection and associated CNS involvement, which resulted in progressive neurological disability over several years. The challenges faced in diagnosing new neurological symptoms in patients undergoing immunosuppressive cancer treatment underscore the need for an interdisciplinary diagnostic approach that includes HEV testing. We propose a diagnostic pathway for future validation in immunocompromised cohorts presenting with neurological symptoms, emphasizing its potential to enhance clinical outcomes.