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In Bavaria, the exploration of geothermal energy from the carbonates in the Upper Jurassic reservoir is a promising and growing field, but the efficiency is seriously affected by scaling, i.e., the precipitation of CaCO3. Predictive maintenance tools aim to reduce service intervals and unexpected downtimes based on measurements and a prediction of the state of the installations. With regard to scaling, this requires forward modeling of carbonate precipitation. However, standard models overpredict the amount of precipitates, and data required for localized process parametrization under dynamic flow conditions is scarce. For hybrid multiphase models, this data has to include local hydrogeochemistry, shear forces, and interaction forces of the precipitates with the matrix. Our new experimental approach combines the quantitative measurement of the amount of precipitates using a highly sensitive quartz crystal microbalance (QCM) measurement with the qualitative analysis of the individual crystals with Raman microspectroscopy. The setup consists of a microfluidic flow channel in which NaOH solution and Munich tap water (carbonate-rich) were injected and allowed to mix under varying flow conditions. The increase in the pH value caused nucleation and precipitation, which was monitored in real-time. The experiments showed many newly formed carbonate particles, but only some of the particles were actually deposited on the QCM crystal. The remaining particles were not able to settle at the given flow velocities and flushed out of the microfluidic channel. The stability of the signal degraded in long-term experiments. Therefore, quantitative measurements are limited to shorter times (up to 1 day in our case) with semi-quantitative data beyond that time. For those short time frames, the combination of Raman microscopy and QCM allows to quantify the process of scaling formation under very controlled dynamic conditions.

Abstract Background Increased levels of physical activity are associated with a reduction of breast cancer mortality, especially in postmenopausal women with positive hormone receptor status. So far, previous observational case–control and cohort studies have focused on associations between overall leisure time physical activity and survival of women with breast cancer in general. Methods In this multicenter prospective cohort study, conducted in Germany between 30th August 2012 to 29th December 2017, we investigated general physical activity in a homogenous sample of n = 1440 postmenopausal women with advanced (inoperable locally advanced or metastatic), hormone receptor-positive breast cancer receiving the same therapy (everolimus and exemestane). Self-reported physical activity was assessed using the Godin Leisure Time Exercise Questionnaire (GLTEQ) before and every 3 months during treatment. Participants were then classified into “active” and “insufficiently active” to screen their activity behavior the week prior to medical treatment. In addition, changes in physical activity patterns were assessed. Adjusted Cox regression analyses were performed for the activity categories to determine hazard ratios (HR). Besides progression-free survival (PFS), adverse events (AEs), QoL, and fatigue were assessed every 3 months until study termination. Results Compared to “insufficiently active” patients, “active” individuals indicated a significantly longer PFS (HR: 0.84 [0.74; 0.984], p = .0295). No significant differences were observed for changes of physical activity behavior. Patients who reported to be “active” at baseline revealed significantly fewer AEs compared to “insufficiently” active patients. In detail, both severe and non-severe AEs occurred less frequently in the “active” patients group. In line with that, QoL and fatigue were better in physical “active” patients compared to their insufficient active counterparts at the last post-baseline assessment. Participants who remained or become active indicated less AEs, a higher QoL, and reduced fatigue levels. Conclusions Physical activity behavior prior to medical treatment might have prognostic value in patients with advanced breast cancer in terms of extending the PFS. Moreover, physical activity before and during treatment may reduce treatment-related side effects and improve patients’ QoL and fatigue. Trial registration EUPAS9462. Registered 30th October 2012 “retrospectively registered.”

Natural killer (NK) cells are critical for anti-metastatic immunity and can eliminate metastasizing tumor cells within circulation and sites of metastatic seeding. Here, we show that disseminated tumor cells (DTCs) colonizing the mouse lung secrete prostaglandin E2 (PGE 2 ) to locally induce NK cell dysfunction, allowing outgrowing metastases to escape immune control and establish metastatic disease. Mechanistically, PGE 2 signaling through its receptors EP2 and EP4 mediates NK cell dysfunction, which leads to reprogramming of NK cell gene expression and results in impaired production of anti-metastatic cytokines. In human cancer patients, the PGE 2 -EP2/EP4 axis is associated with NK cell dysfunction within distant organ metastases. Disabling EP2/EP4 signaling in NK cells prevents their dysfunction in DTC-colonized lungs and achieves effective NK cell-mediated control of metastatic disease. Our findings reveal a suppressive signaling axis exploited by metastasizing tumor cells to escape immune control in distant organs that could be targeted for metastatic cancer therapy., Competing Interests: Declaration of interests A.-M.P. and J.P.B. have filed a patent application (EP4234684) including work in this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematodermic neoplasm usually involving the skin. In this retrospective case series, 10 cases of BPDCN were identified, 90% of which had skin involvement and exhibited predominantly violaceous nodules and/or bruise-like plaques. Skin lesions showed diffuse or nodular dermal-based infiltrates of intermediate sized blasts with a Grenz zone. Tumor immunophenotyping was CD4(+), CD56(+), CD123(+) and CD303(+). The most frequently mutated genes according to targeted next-generation sequencing were TET2 (3/7) and NRAS (2/7). Multiagent chemotherapy (CT) was administered as first-line therapy, and a total of 5 patients underwent allogenic hematopoietic stem cell transplantation (allo-HSCT). Better outcomes were observed in younger patients and those treated with acute lymphoblastic leukemia (ALL)-like CT followed by allo-HSCT. This study shows the clinical range of cutaneous lesions of BPDCN. Despite the absence of a gold standard therapy, patients treated with myeloablative intensive regimens and allo-HSCT seems to have a more favorable prognosis., Competing Interests: Conflicto de intereses Los autores declaran no tener ningún conflicto de intereses., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Testicular large B-cell lymphoma (TLBCL) is an infrequent and aggressive lymphoma arising in an immune-privileged site and has recently been recognized as a distinct entity from diffuse large B-cell lymphoma (DLBCL). We describe the genetic features of TLBCL and compare them with published series of nodal DLBCL and primary large B-cell lymphomas of the CNS (PCNSL). We collected 61 patients with TLBCL. We performed targeted next-generation sequencing, copy number arrays, and fluorescent in situ hybridization to assess chromosomal rearrangements in 40 cases with available material. Seventy percent of the cases showed localized stages. BCL6 rearrangements were detected in 36% of cases, and no concomitant BCL2 and MYC rearrangements were found. TLBCL had fewer copy number alterations ( p  < 0.04) but more somatic variants ( p  < 0.02) than nodal DLBCL and had more frequent 18q21.32-q23 ( BCL2 ) gains and 6q and 9p21.3 ( CDKN2A/B ) deletions. PIM1 , MYD88 L265P , CD79B , TBL1XR1 , MEF2B , CIITA , EP300, and ETV6 mutations were more frequent in TLBCL, and BCL10 mutations in nodal DLBCL. There were no major genetic differences between TLBCL and PCNSL. Localized or disseminated TLBCL displayed similar genomic profiles. Using LymphGen, the majority of cases were classified as MCD. However, we observed a subgroup of patients classified as BN2, both in localized and disseminated TLBCL, suggesting a degree of genetic heterogeneity in the TLBCL genetic profile. TLBCL has a distinctive genetic profile similar to PCNSL, supporting its recognition as a separate entity from DLBCL and might provide information to devise targeted therapeutic approaches., Competing Interests: Ferran Nadeu has received honoraria from Janssen, AbbVie, AstraZeneca, and SOPHiA GENETICS for speaking at educational activities; has received research support from Gilead; and has licensed the use of the protected IgCaller algorithm to Diagnóstica Longwood. Tycho Baumann has received consulting fees or honoraria from Janssen, Roche, Novartis, Merck, Gilead/Kite, Incyte, Lilly, Abbvie, AstraZeneca, and BeiGene. Alejandro Martin García‐Sancho has received consulting fees or honoraria from Janssen, Roche, BMS/Celgene, Kyowa Kirin, Clinigen, EUSAPharma, Novartis, Gilead/Kite, Incyte, Lilly, Takeda, ADC Therapeutics America, Miltenyi, Ideogen, Abbvie, and BeiGene. Elías Campo has been a consultant for GenMab, and Takeda; has received research support from AstraZeneca; received honoraria from Janssen, EUSPharma, Takeda, and Roche for speaking at educational activities; and is an inventor on a Lymphoma and Leukemia Molecular Profiling Project patent “Method for subtyping lymphoma subtypes by means of expression profiling” (PCT/US2014/64161) and a bioinformatic tool (IgCaller) licensed to Diagnostic Longwood. Eva Giné has received honoraria or consulting fees from Gilead, Kite Pharma, Janssen, Genmab, Miltenyi, and Lilly; has received research support from Janssen and travel expenses from Gilead and Kite Pharma. Armando López Guillermo served on the advisory board of Roche, Celgene, Novartis, and Gilead/Kite, received grants from Celgene and Gilead/Kite, and travel expenses from Kite/Gilead. The remaining authors declare no competing interests., (© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra of the midbrain. Familial cases of PD are often caused by mutations of PTEN-induced kinase 1 (PINK1) and the ubiquitin ligase Parkin, both pivotal in maintaining mitochondrial quality control. CISD1, a homodimeric mitochondrial iron-sulfur-binding protein, is a major target of Parkin-mediated ubiquitination. We here discovered a heightened propensity of CISD1 to form dimers in Pink1 mutant flies and in dopaminergic neurons from PINK1 mutation patients. The dimer consists of two monomers that are covalently linked by a disulfide bridge. In this conformation CISD1 cannot coordinate the iron-sulfur cofactor. Overexpressing Cisd, the Drosophila ortholog of CISD1, and a mutant Cisd incapable of binding the iron-sulfur cluster in Drosophila reduced climbing ability and lifespan. This was more pronounced with mutant Cisd and aggravated in Pink1 mutant flies. Complete loss of Cisd, in contrast, rescued all detrimental effects of Pink1 mutation on climbing ability, wing posture, dopamine levels, lifespan, and mitochondrial ultrastructure. Our results suggest that Cisd, probably iron-depleted Cisd, operates downstream of Pink1 shedding light on PD pathophysiology and implicating CISD1 as a potential therapeutic target., Competing Interests: SB, TB, CW, MA, LR, PZ, TS, IR, VV, BM, EH, GA, RK, LZ, AM No competing interests declared, (© 2024, Bitar et al.)

Inflammation including immunothrombosis by neutrophil extracellular traps (NETs) has important implications in acute ischemic stroke and can affect reperfusion status, susceptibility to stroke associated infections (SAI) as well as functional clinical outcome. NETs were shown to be prevalent in stroke thrombi and NET associated markers were found in stroke patients' blood. However, little is known whether blood derived NET markers reflect the amount of NETs in thrombi. Conclusions from blood derived markers to thrombus composition might open avenues for novel strategies in diagnostic and therapeutic approaches. We prospectively recruited 166 patients with acute ischemic stroke undergoing mechanical thrombectomy between March 2018 and May 2021. Available thrombi (n = 106) were stained for NET markers DNA-histone-1 complexes and myeloperoxidase (MPO). Cell free DNA (cfDNA), deoxyribonuclease (DNase) activity, MPO-histone complexes and a cytokine-panel were measured before thrombectomy and after seven days. Clinical data, including stroke etiology, reperfusion status, SAI and functional outcome after rehabilitation, were collected of all patients. NET markers were present in all thrombi. At onset the median concentration of cfDNA in blood was 0.19 µg/ml increasing to 0.30 µg/ml at 7 days. Median DNase activity at onset was 4.33 pmol/min/ml increasing to 4.96 pmol/min/ml at 7 days. Within thrombi DNA-histone-1 complexes and MPO correlated with each other (ρ = 0.792; p < 0.001). Moreover, our study provides evidence for an association between the amount of NETs and endogenous DNase activity in blood with amounts of NETs in cerebral thrombi. However, these associations need to be confirmed in larger cohorts, to investigate the potential clinical implications for individualized therapeutic and diagnostic approaches in acute ischemic stroke., (© 2024. The Author(s).)

Background: We are obliged to give babies the chance to profit from a nationwide screening of developmental dysplasia of the hip in very rural areas of Mongolia, where trained physicians are scarce. This study aimed to compare the quality and interpretation of hip ultrasound screening examinations performed by nurses and junior physicians., Methods: A group of 6 nurses and 6 junior physician volunteers with no previous ultrasound experience underwent Graf's standard training in hands-on practice. Newborns were examined before discharge from the hospital, according to the national guideline. Two standard documentation images of each hip were saved digitally. The groups were compared on the proportion of good quality of sonograms and correct interpretation. Two Swiss supervisors' agreed diagnosis according to Graf was considered the final reference for the study purposes., Results: A total of 201 newborns (402 hips or 804 sonograms) were examined in the study, with a mean age of 1.3±0.8 days at examination. Junior physicians examined 100 newborns (200 hips or 400 sonograms), while nurses examined 101 newborns (202 hips or 404 sonograms). The study subjects of the two groups were well balanced for the distribution of baseline characteristics. The study observed no statistically significant difference in the quality of Graf's standard plane images between the providers. Eventually, 92.0% (92) of the physician group and 89.1% (90) of the nurse group were correctly diagnosed as "Group A" (Graf's Type 1 hip) or "Non-Group A" hips (p = 0.484). The most common errors among the groups were a missing lower limb, wrong measurement lines, and technical problems., Conclusion: Our study provides evidence that while there might be a trend of slightly more technical mistakes in the nurse group, the overall diagnosis accuracy is similar to junior physicians after receiving standard training in Graf's hip ultrasound method. However, after basic training, regular quality control is a must and all participants should receive refresher trainings. More specifically, nurses need training in the identification of anatomical structures., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ulziibat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Ebullition transports large amounts of the potent greenhouse gas methane (CH 4 ) from aquatic sediments to the atmosphere. River beds are a main source of biogenic CH 4 , but emission estimates and the relative contribution of ebullition as a transport pathway are poorly constrained. This study meets a need for more direct measurements with a whole-year data set on CH 4 ebullition from a small stream in southern Germany. Four gas traps were installed in a cross section in a river bend, representing different bed substrates between undercut and slip-off slope. For a comparison, diffusive fluxes were estimated from concentration gradients in the sediment and from measurements of dissolved CH 4 in the surface water. The data revealed highest activity with gas fluxes above 1000 ml m - 2  d - 1 in the center of the stream, sustained ebullition during winter, and a larger contribution of ebullitive compared to diffusive CH 4 fluxes. Increased gas fluxes from the center of the river may be connected to greater exchange with the surface water, thus increased carbon and nutrient supply, and a higher sediment permeability for gas bubbles. By using stable isotope fractionation, we estimated that 12-44% of the CH 4 transported diffusively was oxidized. Predictors like temperature, air pressure drop, discharge, or precipitation could not or only poorly explain temporal variations of ebullitive CH 4 fluxes., (© 2024. The Author(s).)