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Summary In atopic patients and patients with hyper-IgE syndrome (HIE) highly elevated IgE serum levels can be detected. Due to their very low frequency little is known about IgE-producing plasma cells (PC) in peripheral blood. We used CD138 MACS microbeads to enrich plasma cells from peripheral blood of normal donors, atopic patients and one HIE patient. CD138+ cells were mainly CD45+ , CD44++ , CD19dim , CD38++ , CD27++ , CD86+ , HLA-DR+/++ , CD71dim , VLA-4+ , VLA-5– , CD28– , CD25– , CD69– , CLA– , CD20– , CD21– and CD22– . They show weak expression of surface Ig but high levels of intracellular Ig and they secrete Ig in culture. Thus CD138+ cells from peripheral blood show characteristics of early plasma cells. IgE+ CD138+ plasma cells could be detected in 19 of 24 normal donors with an average frequency of 0·06% IgE+ cells among CD138+ cells. Higher frequencies were detected in atopic patients, atopic patients with markedly elevated serum IgE levels and the hyper-IgE patient with an average of 0·32%, 7·21% and 6·54%, respectively. Additionally, using the recently developed cellular affinity matrix technology, we were able to detect IgE secreting plasma cells and thereby could demonstrate that most of the IgE secreting cells express CD138. The frequency of IgE+ CD138+ cells among PBMC correlated highly significantly with serum IgE titres (r = 0·8532***), indicating that IgE secreting CD138+ cells in peripheral blood are directly related to the plasma cell pool contributing to the IgE titre. [ABSTRACT FROM AUTHOR]

In proliferating non-erythroid cells, the expression of transferring receptors (TfR) is negatively regulated by the amount of intracellular iron, Fe-dependent regulation of TfR occurs post-transcriptionally and is mediated by iron-responsive elements (IRE) located in the 3' untranslated region of the TfR mRNA. IREs are recognized by a specific cytoplasmic binding protein (IRE-BP) that, in the absence of Fe, binds with high affinity to TfR mRNA, preventing its degradation. While TfR numbers are positively correlated with proliferation in non-erythroid cells, in hemoglobin-synthesizing cells, their numbers increase during differentiation and are, therefore, negatively correlated with proliferation. This suggests a distinct regulation of erythroid TfR expression and evidence, as follows, for this was found in the present study, (a) With nuclear run-on assays, our experiments show increased TfR mRNA transcription following induction of erythroid differentiation of murine erythroleukemia (MEL) with Me2SO, (b) Me2SO treatment of MEL cells does not increase IRE-BP activity which, is however, increased in uninduced MEL cells by Fe chelators, (c) Following induction of MEL cells, there is an increase in the stability of TfR mRNA, whose level is only slightly affected by iron excess, (d) Heme-synthesis inhibitors, such as succinylacetone and isonicotinic acid hydrazide, which inhibit numerous aspects of erythroud differentiation, also inhibit TfR mRNA expression in induced MEL cells. However, heme-synthesis inhibition does not lead to a decrease in TfR mRNA levels in uninudced MEL cells. Thus, these studies indicate that TfR gene expression is regulated differently in hemoglobin synthesizing as compared to uninduced MEL cells. [ABSTRACT FROM AUTHOR]

Major, minor, and trace elements in wines from the Republic of Macedonia were determined in this study. Both inductively coupled plasma–mass spectrometry (ICP-MS) and inductively coupled plasma– optical emission spectrometry (ICP-OES) were used for accurate determination of the concentration of 42 elements (Ag, Al, Au, B, Ba, Be, Bi, Ca, Cd, Ce, Co, Cu, Dy, Er, Eu, Fe, Ga, Gd, Ge, Ho, La, Lu, Mg, Mn, Mo, Na, Nd, Ni, P, Pb, Pr, S, Sm, Tb, Ti, Tl, Tm, U, V, Yb, Zn, Zr) in 25 Macedonian white, rose, and red wines from different wine regions. By means of factor and cluster analyses, the wines were discriminated according to wine type (white vs. red) and geographical origin. The main discriminant elements were B, Ba, Ca, Fe, Mg, Mn, P, and S.

Abstract Background The utility of circulating angiogenic cytokines (CAC) as biomarkers in pancreatic cancer has not been clarified yet. We investigated the expression and prognostic associations of seven CAC in patients with pancreatic cancer. Methods Serum samples were collected preoperatively in patients undergoing surgery for localized pancreatic cancer (n = 74), metastatic pancreatic cancer (n = 24) or chronic pancreatitis (n = 20) and in healthy controls (n = 48). Quantitative enzyme-linked immunosorbent assays and multiplex protein arrays were used to determine circulating levels of VEGF, VEGFR-1, PlGF, PDGF-AA, PDGF-BB, Ang-1 and EGF. Multivariate analyses on cancer-specific survival were performed with a Cox proportional hazards model. Results VEGF (p < 0.0001), PDGF-AA (p < 0.0001), Ang-1 (p = 0.002) and EGF (p < 0.0001) were differentially expressed in patients with pancreatic cancer compared to healthy controls. The presence of lymph node metastases was associated with increased levels of all CAC except for PlGF, whereas there were only minor associations of CAC with other clinicopathologic variables. The multivariate model including the entire angiogenic panel revealed high levels of circulating PDGF-AA (hazard ratio 4.58; 95% confidence interval 1.43 - 14.69) as predictor of poor cancer-specific survival, whereas high levels of PDGF-BB (0.15; 0.15 - 0.88), Ang-1 (0.30; 0.10 - 0.93) and VEGF (0.24; 0.09 - 0.57) were associated with a favorable prognosis. Conclusion Circulating levels of certain angiogenic cytokines correlate with patients' prognosis after resection for pancreatic cancer, if a panel of several CAC is considered simultaneously. These data should be considered in future studies evaluating angiogenic factors as prognostic biomarkers and therapeutic targets in patients with pancreatic cancer.

La sclérodermie systémique n'est pas considérée comme une maladie auto-immune familiale, à la différence du lupus érythémateux systémique. Cependant, des cas familiaux de sclérodermie systémique sont décrits, soulevant la question d'une potentielle héritabilité. Une revue de la littérature a été menée afin d'estimer la fréquence de survenue d'une sclérodermie systémique chez les apparentés au premier degré d'un sujet atteint. La revue de la littérature a été réalisée à l'aide de la base de données PubMed, couvrant une période allant jusqu'en août 2024. Les recherches ont été effectuées via les mots-clés (systemic sclerosis)AND((familial)OR(twins[MeSH Terms])). La prévalence et le risque relatif familial ont été recueillis lorsqu'ils étaient disponibles. Sur les 1391 articles identifiés, 92 ont été sélectionnés pour leur pertinence après un examen des titres et des résumés puis 33 d'entre eux (13 études épidémiologiques descriptives et 20 rapports de cas) ont été inclus dans l'analyse. Au moins 255 patients appartenant à 107 familles de sclérodermie systémique ont été recensées (107 cas index, 148 apparentés au premier degré atteints). La prévalence des cas familiaux de sclérodermie systémique varie entre 1,4 et 5,17 % selon les études. La prévalence de sclérodermie systémique chez les apparentés au premier degré d'un cas index varie entre 0,08 et 3,36 %, avec un risque relatif familial estimé entre 3,07 et 14,3. En France, la prévalence des familles multiplex en 2012 était de 2,4 %, la prévalence de la sclérodermie systémique chez un apparenté au premier degré d'un cas index était de 1,1 % et le risque relatif familial de 3,5 [1]. L'antécédent familial de sclérodermie systémique chez un apparenté au premier degré est un des principaux facteurs de risque de développer la maladie [2]. La prévalence des cas familiaux reste toutefois faible par rapport à la poly-autoimmunité et l'auto-immunité familiale [1,3]. Plusieurs cas rapportés décrivent des apparentés au premier degré atteints de connectivites indifférenciées ou mixtes avec des caractéristiques clinico-biologiques insuffisantes pour les classer en tant que sclérodermies systémiques (critères ACR-EULAR 2017). Le taux de concordance bas chez des jumeaux monozygotes et similaire chez les dizygotes suggère une faible contribution génétique, au profit d'un impact environnemental prépondérant [4]. Il n'est pas décrit de transmission monogénique mais de nombreuses études rapportent des variants génétiques facteurs de risque de sclérodermie systémique (NOTCH4 [5] , IRF5, STAT4 [6]). Par ailleurs, une forme extrême de syndrome autoinflammatoire avec morphées en lien avec des mutations gain de fonction de STAT4 a été rapportée [7]. Les données clinico-biologiques, notamment les auto-anticorps, n'étaient pas systématiquement rapportées dans les études, ne nous permettant pas d'aborder plus finement toutes les caractéristiques de ces familles. Il n'est pas clairement établi si cette faible agrégation familiale reflète la réalité ou si elle est sous-estimée en raison d'une sous-déclaration des antécédents familiaux. La prévalence de la sclérodermie systémique familiale décrite dans la littérature est faible. Il serait intéressant de mettre à jour les données épidémiologiques françaises sur les cas familiaux de sclérodermie systémique et de décrire plus précisément leurs caractéristiques clinico-biologiques, voire génétiques. L'étude de cas « extrêmes » (début précoces pédiatriques, familles multiplex) pourrait aider à mieux comprendre la physiopathologie de cette maladie complexe en identifiant des marqueurs moléculaires prédictifs de son apparition ou de son évolution, cibles pour le développement de nouvelles thérapies. [ABSTRACT FROM AUTHOR]

Competing Interests: Conflicts of interest None disclosed.

Abstract: Spinal cord sarcoidosis (SCS) is an uncommon disease with estimated incidence of 0.4% in patients with systemic sarcoidosis. Spinal cord sarcoidosis typically manifests late in the disease course and significantly contributes to patient morbidity. Therefore, early SCS diagnosis and prompt initiation of therapy are crucial. Herein, we report the case of a 51-year-old man with symptomatic SCS managed by 18 F-FDG PET/MRI, allowing diagnosis and treatment efficacy evaluation of spine involvement. We believe that the increasing clinical availability of hybrid PET/MRI devices will offer new opportunities for optimal management of patients with uncommon severe sarcoidosis localizations, such as nervous system., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The assembly of nanoparticles on surfaces in defined patterns has long been achieved via template-assisted methods that involve long deposition and drying steps and the need for molds or masks to obtain the desired patterns. Control over deposition of materials on surfaces via laser-directed microbubbles is a nascent technique that holds promise for rapid fabrication of devices down to the micrometer scale. However, the influence of surface chemistry on the resulting assembly using such approaches has so far not been studied. Herein, the printing of layered silicate nanoclays using a laser-directed microbubble was established. Significant differences in the macroscale structure of the printed patterns were observed for hydrophilic, pristine layered silicates compared to hydrophobic, modified layered silicates, which provided the first example of how the surface chemistry of such nanoscale objects results in changes in assembly with this approach. Furthermore, the ability of layered silicates to adsorb molecules at the interface was retained, which allowed the fabrication of proof-of-concept sensors based on Förster resonance energy transfer (FRET) from quantum dots embedded in the assemblies to bound dye molecules. The detection limit for Rhodamine 800 sensing via FRET was found to be on the order of 10 -12 M, suggesting signal enhancement due to favorable interactions between the dye and nanoclay. This work sets the stage for future advances in the control of hierarchical assembly of nanoparticles by modification of surface chemistry while also demonstrating a quick and versatile approach to achieve ultrasensitive molecular sensors.

MXenes represent a novel class of 2D materials with unique properties and have great potential for diverse applications in sensing and electronics; however, their directed assembly at interfaces has not yet been achieved. Herein, the plasmonic heating of MXenes was exploited to achieve the controlled deposition of MXene assemblies via a laser-directed microbubble. The influence of various factors such as solvent composition, substrate surface chemistry, MXene concentration, and laser fluence was investigated, establishing the optimal conditions for rapid patterning with good fidelity. Printed MXene assemblies showed good electrical conductivity and plasmonic sensing capabilities and were able to meet or exceed the state of the art without additional postprocessing steps. This represents the first study of a directed approach for microfabrication using MXenes and lays the foundation for future work in optically directed assembly of MXenes and MXene-based nanocomposites at interfaces toward sensors and devices.

Background: Regional deprivation indices enable researchers to analyse associations between socioeconomic disadvantages and health outcomes even if the health data of interest does not include information on the individuals' socioeconomic position. This article introduces the recent revision of the German Index of Socioeconomic Deprivation (GISD) and presents associations with life expectancy as well as age-standardised cardiovascular mortality rates and cancer incidences as applications., Methods: The GISD measures the level of socioeconomic deprivation using administrative data of education, employment, and income situations at the district and municipality level from the INKAR database. The indicators are weighted via principal component analyses. The regional distribution is depicted cartographically, regional level associations with health outcomes are presented., Results: The principal component analysis indicates medium to high correlations of the indicators with the index subdimensions. Correlation analyses show that in districts with the lowest deprivation, the average life expectancy of men is approximately six years longer (up to three years longer for women) than for those from districts with the highest deprivation. A similar social gradient is observed for cardiovascular mortality and lung cancer incidence., Conclusions: The GISD provides a valuable tool to analyse socioeconomic inequalities in health conditions, diseases, and their determinants at the regional level., Competing Interests: Conflict of interest The authors report the following conflict(s) of interest: Fabian Tetzlaff is financed from project funds from the Stiftung Deutsche Krebshilfe, project: ‘Regionale sozioökonomische Ungleichheit im Krebsgeschehen in Deutschland’ (regional socioeconomic inequity in cancer in Germany). Lars Eric Kroll leads the Department of Data Science and Systems Analysis at the Central Research Institute of Ambulatory Health Care in Germany, the Associations of Statutory Health Insurance Physicians and the National Association of Statutory Health Insurance Physicians sponsor the foundation., (© Robert Koch Institute. All rights reserved unless explicitly granted.)

The steady release of anthropogenic toxins into the biosphere is compromising water security globally. Herein, CoAl layered double hydroxide, a clay-like layered material with a cationic surface charge, was organically modified and used to template the growth of Bi 2 MoO 6 . The resulting nanohybrid selectively removed the anionic dye methyl orange from aqueous solution and showed an enhancement of greater than 300% in the maximum adsorptivity (1.95 mmol/g) compared to modified CoAl layered double hydroxide (0.42 mmol/g). Interestingly, the observed improvement in adsorption occurs without any significant increase in the surface area of the hybrids. Furthermore, these hybrids exhibit increased broadband visible light absorption, and their photoactivity is slightly improved compared to CoAl layered double hydroxide. This study demonstrates that composites of clay-like materials with Aurivillius oxides are promising sorbent materials for water decontamination and photocatalytic antifouling membranes and shows that the synthetic strategy that was first established with an anionic layered silicate nanoclay can be generalized to other ionic layered materials.

Background: Nivolumab monotherapy is approved for the treatment of advanced renal cell carcinoma (aRCC) after prior therapy on the basis of results from CheckMate 025., Objective: The NORA (NivOlumab in Renal cell cArcinoma) noninterventional study (NIS) aims to capture real-world data to complement the pivotal CheckMate 025 clinical trial., Design, Setting, and Participants: NORA is a prospective, multicenter NIS in Germany. Consenting patients with aRCC of any subtype who started nivolumab after previous therapy were eligible., Outcome Measurements and Statistical Analysis: The primary objective was to estimate overall survival (OS) in the overall population and relevant subgroups. Secondary objectives included progression-free survival (PFS), the objective response rate (ORR), the duration of response (DOR), safety, and patient-reported outcomes (PROs). Baseline characteristics were summarized using descriptive statistics. OS and PFS were estimated via the Kaplan-Meier-method., Results and Limitations: A total of 228 patients with aRCC were eligible. The median age was 70 yr, 71% were male, 14% had favorable, 58% had intermediate, and 15% had poor International Metastatic RCC Database Consortium risk (12% missing information). The median follow-up was 37 mo. In the overall population, median OS was 24 mo (95% confidence interval [CI] 19-28) and median PFS was 5.3 mo (95% CI 3.9-6.7). The ORR was 20% and the median DOR was 28 mo (95% CI 16-not estimable). No new safety signals emerged (46% and 15% of patients had treatment-related adverse events of all grades and grade 3-4, respectively; there was 1 treatment-related death due to liver failure). PROs did not reveal detriments during the study duration. Limitations include the lack of central pathology review and no standardization for imaging evaluation and toxicity assessment., Conclusions: Effectiveness and safety in this real-world population were in line with the pivotal clinical trial and support the use of nivolumab after prior systemic therapy in a broad aRCC population., Patient Summary: Nivolumab is an antibody treatment approved for patients with advanced kidney cancer who have already received systemic therapy. Its approval was based on results from a clinical trial. Our study demonstrates its effectiveness and safety in "real-world" patients., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Groundwater is being depleted globally at an average rate of more than one meter per year, during a period when more than a quarter of the human population has no access to potable water. Aside from overexploitation, freshwater security is also threatened by climate change and chemical pollution. The contamination of surface and groundwater by industrial substances is also undermining the vitality of ecosystems. It was previously shown that {100}-faceted Bi 2 MoO 6 -Laponite hybrids effectively bind and photodegrade molecular species, aiding in the decontamination of water. In this study, the encapsulation of Bi 2 MoO 6 -Laponite particles with the polymers butyl acrylate and styrene further enhanced adsorption of methylene blue by 31.4%, with a specific adsorption capacity of 192 μmol/g. The polymer-particle composites were deposited to form membranes and their efficacies in water filtration and photodegradation were examined. Among the different surface modifications examined, the highest dye sorption was obtained by butyl acrylate and styrene (3:2) with a 5 mol % cross-linker. This study provides a method for enhancing the molecular adsorption of composite particles used in membranes capable of multiple cycles of adsorption and photodegradation, advancing the application of such systems to water filtration.

Certain nanomaterials can filter and alter unwanted compounds due to a high surface area, surface reactivity, and microporous structure. Herein, γ-Bi 2 MoO 6 particles are synthesized via a colloidal hydrothermal approach using organically modified Laponite as a template. This organically modified Laponite interlayer serves as a template promoting the growth of the bismuth molybdate crystals in the [010] direction to result in hybrid Laponite-Bi 2 MoO 6 particles terminating predominantly in the {100} crystal facets. This resulted in an increase in particle size from lateral dimensions of <100 nm to micron scale and superior adsorption capacity compared to bismuth molybdate nanoparticles. These {100}-facet terminated particles can load both cationic and anionic dyes on their surfaces near-spontaneously and retain the photocatalytic properties of Bi 2 MoO 6 . Furthermore, dye-laden hybrid particles quickly sediment, rendering the task of particle recovery trivial. The adsorption of dyes is completed within minutes, and near-complete photocatalytic degradation of the adsorbed dye in visible light allowed recycling of these particles for multiple cycles of water decontamination. Their adsorption capacity, facile synthesis, good recycling performance, and increased product yield compared to pure bismuth molybdate make them promising materials for environmental remediation. Furthermore, this synthetic approach could be exploited for facet engineering in other Aurivillius-type perovskites and potentially other materials.

Designing nanostructures with extended light absorption via defect engineering is a useful approach for the synthesis of efficient photocatalysts. Herein, ZnIn 2 S 4 was grown hydrothermally in the modified interlayer space of Laponite, resulting in lamellae consisting of Zn-defective ZnIn 2 S 4 several unit cells thick. In the process it was found that Mg 2+ leached from Laponite during synthesis led to the formation of Zn defects in ZnIn 2 S 4 . This resulted in nanohybrids with light absorption extended across the visible spectrum and in improved charge transfer due to the layered structure formed via confined growth. Compared with pure ZnIn 2 S 4 , Zn-defective ZnIn 2 S 4 -Laponite hybrids have increased photocurrent generation and photocatalytic performance. The leaching of Mg 2+ and the resulting formation of Zn defects was attenuated by addition of 4 mM Mg 2+ to the reaction, due to a combination of shifting of the equilibrium of Mg 2+ leaching toward stability, and increased ionic strength. In summary, this work demonstrates the growth of ∼1 nm thick lamellae of ZnIn 2 S 4 , presents a unique strategy to generate cation defects in nanomaterials and the mechanism behind it, and also provides an approach to mitigate Mg 2+ leaching in such syntheses.

The management of lymphoma in patients with primary immunodeficiency (PID) is challenging because of its poor prognosis and complex therapeutic approaches. We conducted a systematic literature review of case-reports, case-series, and cohorts indexed in MEDLINE reporting the association of lymphoma and PID. One hundred and eighty-two articles were selected out of 787. We identified 386 cases. Median age at diagnosis of PID and lymphoma was 9.5 and 12 years old, respectively. T-cell deficiencies were the main PIDs associated with lymphoma (57%). The most prevalent lymphoma was diffuse large B-cell lymphoma (33.5%). Epstein-Barr Virus-driven lymphomas were mostly observed in innate immunodeficiencies (when reported). Complete response to treatment was observed in 65.8% of the cases. Death occurred in 38.2%. Few allogenic stem cell transplantations were performed (29 cases). Our detailed analysis of the literature provides a landscape of lymphoma's occurrence in PID. Devoted studies in specific sub-groups of patients at risk are needed to develop dedicated protocols.