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Understanding interactions between antibiotics used in combination is an important theme in microbiology. Using the interactions between the antifolate drug trimethoprim and the ribosome-targeting antibiotic erythromycin in Escherichia coli as a model, we applied a transcriptomic approach for dissecting interactions between two antibiotics with different modes of action. When trimethoprim and erythromycin were combined, the transcriptional response of genes from the sulfate reduction pathway deviated from the dominant effect of trimethoprim on the transcriptome. We successfully altered the drug interaction from additivity to suppression by increasing the sulfate level in the growth environment and identified sulfate reduction as an important metabolic determinant that shapes the interaction between the two drugs. Our work highlights the potential of using prioritization of gene expression patterns as a tool for identifying key metabolic determinants that shape drug-drug interactions. We further demonstrated that the sigma factor-binding protein gene crl shapes the interactions between the two antibiotics, which provides a rare example of how naturally occurring variations between strains of the same bacterial species can sometimes generate very different drug interactions.

Abstract After 53 years of quiescence, Mount Agung awoke in August 2017, with intense seismicity, measurable ground deformation, and thermal anomalies in the summit crater. Although the seismic unrest peaked in late September and early October, the volcano did not start erupting until 21 November. The most intense explosive eruptions with accompanying rapid lava effusion occurred between 25 and 29 November. Smaller infrequent explosions and extrusions continue through the present (June 2019). The delay between intense unrest and eruption caused considerable challenges to emergency responders, local and national governmental agencies, and the population of Bali near the volcano, including over 140,000 evacuees. This paper provides an overview of the volcanic activity at Mount Agung from the viewpoint of the volcano observatory and other scientists responding to the volcanic crisis. We discuss the volcanic activity as well as key data streams used to track it. We provide evidence that magma intruded into the mid-crust in early 2017, and again in August of that year, prior to intrusion of an inferred dike between Mount Agung and Batur Caldera that initiated an earthquake swarm in late September. We summarize efforts to forecast the behavior of the volcano, to quantify exclusion zones for evacuations, and to work with emergency responders and other government agencies to make decisions during a complex and tense volcanic crisis.

Background Air trapping and lung hyperinflation are major determinants of prognosis and response to therapy in chronic obstructive pulmonary disease (COPD). They are often determined by body plethysmography, which has limited availability, and so the question arises as to what extent they can be estimated via spirometry. Methods We used data from visits 1–5 of the COPD cohort COSYCONET. Predictive parameters were derived from visit 1 data, while visit 2–5 data was used to assess reproducibility. Pooled data then yielded prediction models including sex, age, height, and body mass index as covariates. Hyperinflation was defined as ratio of residual volume (RV) to total lung capacity (TLC) above the upper limit of normal. (ClinicalTrials.gov identifier: NCT01245933). Results Visit 1 data from 1988 patients (Global Initiative for Chronic Obstructive Lung Disease grades 1–4, n=187, 847, 766, 188, respectively) were available for analysis (n=1231 males, 757 females; mean±sd age 65.1±8.4 years; forced expiratory volume in 1 s (FEV1) 53.1±18.4 % predicted (% pred); forced vital capacity (FVC) 78.8±18.8 % pred; RV/TLC 0.547±0.107). In total, 7157 datasets were analysed. Among measures of hyperinflation, RV/TLC showed the closest relationship to FEV1 % pred and FVC % pred, which were sufficient for prediction. Their relationship to RV/TLC could be depicted in nomograms. Even when neglecting covariates, hyperinflation was predicted by FEV1 % pred, FVC % pred or their combination with an area under the curve of 0.870, 0.864 and 0.889, respectively. Conclusions The degree of air trapping/hyperinflation in terms of RV/TLC can be estimated in a simple manner from forced spirometry, with an accuracy sufficient for inferring the presence of hyperinflation. This may be useful for clinical settings, where body plethysmography is not available.

The concept of central sleep apnoea or hypoventilation encompasses hypercapnic central hypoventilation, such as obesity hypoventilation syndrome and eucapnic or hypocapnic central sleep apnoea. Among subjects with eucapnic or hypocapnic central sleep apnoea, several therapeutic options are available for those with Cheyne–Stokes respiration (CSR). CSR is frequent in patients with New York Heart Association stage III and IV chronic heart failure, and in various neurological disorders. In these patients, treatment modalities include optimising cardiac condition and drugs, such as theophylline, acetazolamide and/or oxygen. Ventilatory support, such as nasal continuous positive airway pressure (CPAP), bi-level pressure support, or adaptive servo-ventilation (ASV), has been shown to improve CSR in patients with cardiac failure; however, convincing evidence that nasal CPAP improves life expectancy in these patients is lacking. Nevertheless, the treatment of associated obstructive sleep-disordered breathing is indicated per se, as it may improve cardiac function. There is currently no proof that bi-level ventilation is superior to nasal CPAP. The few available studies that have focused on ASV have shown satisfactory control of CSR in cardiac failure patients. While ASV is not a first-line treatment choice, it appears to be superior to oxygen, CPAP and bi-level pressure ventilation in controlling the apnoea/hypopnea index and probably sleep fragmentation. As yet there are no data on mortality and, as such, firm conclusions cannot be drawn as to the role of ASV in the management of cardiac failure patients suffering from CSR. Obesity-related hypoventilation has increased dramatically over recent decades due to the epidemic increase in obesity in the developed countries. Obesity hypoventilation syndrome predisposes to the development of pulmonary hypertension and cor pulmonale. Noninvasive home ventilation is increasingly applied in obese patients with hypercapnic respiratory failure, however, initial mechanical ventilatory support can be reduced to nasal continuous positive airway pressure in only a subset of these individuals.

Objective. To estimate level of adherence to oral calcium and vitamin D supplementation as well as bisphosphonate amongst patients with PMR and GCA treated with glucocorticoids. Method. A total of 138 patients with the diagnosis of PMR and/or GCA registered in our department in December 2013. In this cross-sectional study we interviewed all the patients to measure level of adherence to calcium and vitamin D, as well as bisphosphonates. Results. Out of the 118 included patients, 88.9% of them were adherent to their prescription. Only 2 patients (1.7%) did not take calcium and vitamin D at all and 10 patients (8.5%) took their medication infrequently, 9 and 1 out of 10 patients took the medication 50–100% of the time and less than 50% of the prescribed dose, respectively. Sixty-one patients received additional treatment with bisphosphonate and 96.6% were adherent to this therapy. The remaining 3.4% of the patients did not take the medication at all. Forgetfulness, adverse side effects, and lack of understanding of treatment benefits were the most significant causes for nonadherence to calcium and vitamin D. Conclusions. Contrary to what we expected this study found that adherence to osteoporosis preventive medication in patients with PMR and GCA was high.

Key to our ability to increase recombinant protein production through secretion is a better understanding of the pathways that interact to translate, process and export mature proteins to the surrounding environment, including the supporting cellular machinery that supplies necessary energy and building blocks. By combining droplet microfluidic screening with large-scale CRISPR libraries that perturb the expression of the majority of coding and non-coding genes in S. cerevisiae, we identified 345 genes for which an increase or decrease in gene expression resulted in increased secretion of α-amylase. Our results show that modulating the expression of genes involved in the trafficking of vesicles, endosome to Golgi transport, the phagophore assembly site, the cell cycle and energy supply improve α-amylase secretion. Besides protein-coding genes, we also find multiple long non-coding RNAs enriched in the vicinity of genes associated with endosomal, Golgi and vacuolar processes. We validated our results by overexpressing or deleting selected genes, which resulted in significant improvements in α-amylase secretion. The advantages, in terms of precision and speed, inherent to CRISPR based perturbations, enables iterative testing of new strains for increased protein secretion. [ABSTRACT FROM AUTHOR]

Dose–response relationships are a general concept for quantitatively describing biological systems across multiple scales, from the molecular to the whole‐cell level. A clinically relevant example is the bacterial growth response to antibiotics, which is routinely characterized by dose–response curves. The shape of the dose–response curve varies drastically between antibiotics and plays a key role in treatment, drug interactions, and resistance evolution. However, the mechanisms shaping the dose–response curve remain largely unclear. Here, we show in Escherichia coli that the distinctively shallow dose–response curve of the antibiotic trimethoprim is caused by a negative growth‐mediated feedback loop: Trimethoprim slows growth, which in turn weakens the effect of this antibiotic. At the molecular level, this feedback is caused by the upregulation of the drug target dihydrofolate reductase (FolA/DHFR). We show that this upregulation is not a specific response to trimethoprim but follows a universal trend line that depends primarily on the growth rate, irrespective of its cause. Rewiring the feedback loop alters the dose–response curve in a predictable manner, which we corroborate using a mathematical model of cellular resource allocation and growth. Our results indicate that growth‐mediated feedback loops may shape drug responses more generally and could be exploited to design evolutionary traps that enable selection against drug resistance. Synopsis: Growth‐rate dependent sensitivity of E. coli to the antibiotic trimethoprim leads to a negative feedback loop that explains the extreme shallowness of the dose‐response curve. This feedback loop is mediated by the regulation of the drug target dihydrofolate reductase (DHFR). Reducing the growth rate generally renders E. coli less sensitive to the antibiotic trimethoprim.This effect leads to a negative feedback loop, which causes the extreme shallowness of the trimethoprim dose‐response curve.Growth‐rate dependent regulation of the drug target dihydrofolate reductase (DHFR) mediates this feedback loop.A mathematical model of cellular resource allocation accurately captures these phenomena. [ABSTRACT FROM AUTHOR]

Understanding interactions between antibiotics used in combination is an important theme in microbiology. Using the interactions between the antifolate drug trimethoprim and the ribosome-targeting antibiotic erythromycin in Escherichia coli as a model, we applied a transcriptomic approach for dissecting interactions between two antibiotics with different modes of action. When trimethoprim and erythromycin were combined, the transcriptional response of genes from the sulfate reduction pathway deviated from the dominant effect of trimethoprim on the transcriptome. We successfully altered the drug interaction from additivity to suppression by increasing the sulfate level in the growth environment and identified sulfate reduction as an important metabolic determinant that shapes the interaction between the two drugs. Our work highlights the potential of using prioritization of gene expression patterns as a tool for identifying key metabolic determinants that shape drug-drug interactions. We further demonstrated that the sigma factor-binding protein gene crl shapes the interactions between the two antibiotics, which provides a rare example of how naturally occurring variations between strains of the same bacterial species can sometimes generate very different drug interactions. [ABSTRACT FROM AUTHOR]

In Escherichia coli, the expression of heterologous genes for the production of recombinant proteins can be challenging due to the codon bias of different organisms. The rare codons AGG and AGA are among the rarest in E. coli. In this work, by using the human gene RioK2 as case study, we found that the presence of consecutive AGG‐AGA led to a premature stop, which may be caused by an event of −1 frameshift. We found that translational problems caused by consecutive AGG‐AGA are sequence dependent, in particular, in sequences that contain multiple rare AGG or AGA codons elsewhere. Translational problems can be alleviated by different strategies, including codon harmonization, codon optimization, or by substituting the consecutive AGG‐AGA codons by more frequent arginine codons. Overall, our results furthered our understanding about the relationship between consecutive rare codons and translational problems. Such information will aid the design of DNA sequence for the production of recombinant proteins. [ABSTRACT FROM AUTHOR]

Background: Metabolic engineering and synthetic biology of cyanobacteria offer a promising sustainable alternative approach for fossil-based ethylene production, by using sunlight via oxygenic photosynthesis, to convert carbon dioxide directly into ethylene. Towards this, both well-studied cyanobacteria, i.e., Synechocystis sp PCC 6803 and Synechococcus elongatus PCC 7942, have been engineered to produce ethylene by introducing the ethylene-forming enzyme (Efe) from Pseudomonas syringae pv. phaseolicola PK2 (the Kudzu strain), which catalyzes the conversion of the ubiquitous tricarboxylic acid cycle intermediate 2-oxoglutarate into ethylene. Results: This study focuses on Synechocystis sp PCC 6803 and shows stable ethylene production through the integration of a codon-optimized version of the efe gene under control of the Ptrc promoter and the core Shine-Dalgarno sequence (5'-AGGAGG-3') as the ribosome-binding site (RBS), at the slr0168 neutral site. We have increased ethylene production twofold by RBS screening and further investigated improving ethylene production from a single gene copy of efe, using multiple tandem promoters and by putting our best construct on an RSF1010-based broad-hostself-replicating plasmid, which has a higher copy number than the genome. Moreover, to raise the intracellular amounts of the key Efe substrate, 2-oxoglutarate, from which ethylene is formed, we constructed a glycogen-synthesis knockout mutant (ΔglgC) and introduced the ethylene biosynthetic pathway in it. Under nitrogen limiting conditions, the glycogen knockout strain has increased intracellular 2-oxoglutarate levels; however, surprisingly, ethylene production was lower in this strain than in the wild-type background. Conclusion: Making use of different RBS sequences, production of ethylene ranging over a 20-fold difference has been achieved. However, a further increase of production through multiple tandem promoters and a broad-host plasmid was not achieved speculating that the transcription strength and the gene copy number are not the limiting factors in our system. [ABSTRACT FROM AUTHOR]

Polyploidy is a well-described trait in some prokaryotic organisms; however, it is unusual in marine microbes from oligotrophic environments, which typically display a tendency towards genome streamlining. The biogeochemically significant diazotrophic cyanobacterium Trichodesmium is a potential exception. With a relatively large genome and a comparatively high proportion of non-protein-coding DNA, Trichodesmium appears to allocate relatively more resources to genetic material than closely related organisms and microbes within the same environment. Through simultaneous analysis of gene abundance and direct cell counts, we show for the first time that Trichodesmium spp. can also be highly polyploid, containing as many as 100 genome copies per cell in field-collected samples and >600 copies per cell in laboratory cultures. These findings have implications for the widespread use of the abundance of the nifH gene (encoding a subunit of the N2-fixing enzyme nitrogenase) as an approach for quantifying the abundance and distribution of marine diazotrophs. Moreover, polyploidy may combine with the unusual genomic characteristics of this genus both in reflecting evolutionary dynamics and influencing phenotypic plasticity and ecological resilience. [ABSTRACT FROM AUTHOR]

Investigating the physiology of cyanobacteria cultured under a diel light regime is relevant for a better understanding of the resulting growth characteristics and for specific biotechnological applications that are foreseen for these photosynthetic organisms. Here, we present the results of a multiomics study of the model cyanobacterium Synechocystis sp. strain PCC 6803, cultured in a lab-scale photobioreactor in physiological conditions relevant for large-scale culturing. The culture was sparged with N2 and CO2, leading to an anoxic environment during the dark period. Growth followed the availability of light. Metabolite analysis performed with 1Hnuclear magnetic resonance analysis showed that amino acids involved in nitrogen and sulfur assimilation showed elevated levels in the light. Most protein levels, analyzed through mass spectrometry, remained rather stable. However, several high-light-response proteins and stress-response proteins showed distinct changes at the onset of the light period. Microarray-based transcript analysis found common patterns of ~56% of the transcriptome following the diel regime. These oscillating transcripts could be grouped coarsely into genes that were upregulated and downregulated in the dark period. The accumulated glycogen was degraded in the anaerobic environment in the dark. A small part was degraded gradually, reflecting basic maintenance requirements of the cells in darkness. Surprisingly, the largest part was degraded rapidly in a short time span at the end of the dark period. This degradation could allow rapid formation of metabolic intermediates at the end of the dark period, preparing the cells for the resumption of growth at the start of the light period. [ABSTRACT FROM AUTHOR]

Both enantiomers of lactic acid, L-lactic acid and D-lactic acid, can be produced in a sustainable way by a photosynthetic microbial cell factory and thus from CO2, sunlight, and water. Several properties of polylactic acid (a polyester of polymerized lactic acid) depend on the controlled blend of these two enantiomers. Recently, cyanobacterium Synechocystis sp. strain PCC6803 was genetically modified to allow formation of either of these two enantiomers. This report elaborates on the D-lactic acid production achieved by the introduction of a D-specific lactate dehydrogenase from the lactic acid bacterium Leuconostoc mesenteroides into Synechocystis. A typical batch culture of this recombinant strain initially shows lactic acid production, followed by a phase of lactic acid consumption, until production "outcompetes" consumption at later growth stages. We show that Synechocystis is able to use D-lactic acid, but not L-lactic acid, as a carbon source for growth. Deletion of the organism's putative D-lactate dehydrogenase (encoded by slr1556), however, does not eliminate this ability with respect to D-lactic acid consumption. In contrast, D-lactic acid consumption does depend on the presence of glycolate dehydrogenase GlcD1 (encoded by sll0404). Accordingly, this report highlights the need to match a product of interest of a cyanobacterial cell factory with the metabolic network present in the host used for its synthesis and emphasizes the need to understand the physiology of the production host in detail. [ABSTRACT FROM AUTHOR]

Background: Photosynthetic cyanobacteria are attractive for a range of biotechnological applications including biofuel production. However, due to slow growth, screening of mutant libraries using microtiter plates is not feasible. Results: We present a method for high-throughput, single-cell analysis and sorting of genetically engineered L-lactate-producing strains of Synechocystis sp. PCC6803. A microfluidic device is used to encapsulate single cells in picoliter droplets, assay the droplets for L-lactate production, and sort strains with high productivity. We demonstrate the separation of low- and high-producing reference strains, as well as enrichment of a more productive L-lactate-synthesizing population after UV-induced mutagenesis. The droplet platform also revealed population heterogeneity in photosynthetic growth and lactate production, as well as the presence of metabolically stalled cells. Conclusions: The workflow will facilitate metabolic engineering and directed evolution studies and will be useful in studies of cyanobacteria biochemistry and physiology. [ABSTRACT FROM AUTHOR]

Through metabolic engineering cyanobacteria can be employed in biotechnology. Combining the capacity for oxygenic photosynthesis and carbon fixation with an engineered metabolic pathway allows carbon-based product formation from CO 2 , light, and water directly. Such cyanobacterial ‘cell factories’ are constructed to produce biofuels, bioplastics, and commodity chemicals. Efforts of metabolic engineers and synthetic biologists allow the modification of the intermediary metabolism at various branching points, expanding the product range. The new biosynthesis routes ‘tap’ the metabolism ever more efficiently, particularly through the engineering of driving forces and utilization of cofactors generated during the light reactions of photosynthesis, resulting in higher product titers. High rates of carbon rechanneling ultimately allow an almost-complete allocation of fixed carbon to product above biomass. [ABSTRACT FROM AUTHOR]

Background Molecular engineering of the intermediary physiology of cyanobacteria has become important for the sustainable production of biofuels and commodity compounds from CO2 and sunlight by "designer microbes." The chemical commodity product L-lactic acid can be synthesized in one step from a key intermediary metabolite of these organisms, pyruvate, catalyzed by a lactate dehydrogenase. Synthetic biology engineering to make "designer microbes" includes the introduction and overexpression of the product-forming biochemical pathway. For further optimization of product formation, modifications in the surrounding biochemical network of intermediary metabolism have to be made. Results To improve light-driven L-lactic acid production from CO2, we explored several metabolic engineering design principles, using a previously engineered L-lactic acid producing mutant strain of Synechocystis sp. PCC6803 as the benchmark. These strategies included: (i) increasing the expression level of the relevant product-forming enzyme, lactate dehydrogenase (LDH), for example, via expression from a replicative plasmid; (ii) coexpression of a heterologous pyruvate kinase to increase the flux towards pyruvate; and (iii) knockdown of phosphoenolpyruvate carboxylase to decrease the flux through a competing pathway (from phosphoenolpyruvate to oxaloacetate). In addition, we tested selected lactate dehydrogenases, some of which were further optimized through site-directed mutagenesis to improve the enzyme's affinity for the co-factor nicotinamide adenine dinucleotide phosphate (NADPH). The carbon partitioning between biomass and lactic acid was increased from about 5% to over 50% by strain optimization. Conclusion An efficient photosynthetic microbial cell factory will display a high rate and extent of conversion of substrate (CO2) into product (here: L-lactic acid). In the existing CO2-based cyanobacterial cell factories that have been described in the literature, by far most of the control over product formation resides in the genetically introduced fermentative pathway. Here we show that a strong promoter, in combination with increased gene expression, can take away a significant part of the control of this step in lactic acid production from CO2. Under these premises, modulation of the intracellular precursor, pyruvate, can significantly increase productivity. Additionally, production enhancement is achieved by protein engineering to increase co-factor specificity of the heterologously expressed LDH. [ABSTRACT FROM AUTHOR]

Oxygenic photosynthesis will havea key role in a sustainable future. It is therefore significant thatthis process can be engineered in organisms such as cyanobacteriato construct cell factories that catalyze the (sun)light-driven conversionof CO2and water into products like ethanol, butanol, orother biofuels or lactic acid, a bioplastic precursor, and oxygenas a byproduct. It is of key importance to optimize such cell factoriesto maximal efficiency. This holds for their light-harvesting capabilitiesunder, for example, circadian illumination in large-scale photobioreactors.However, this also holds for the “dark” reactions ofphotosynthesis, that is, the conversion of CO2, NADPH,and ATP into a product. Here, we present an analysis, based on metaboliccontrol theory, to estimate the optimal capacity for product formationwith which such cyanobacterial cell factories have to be equipped.Engineered l-lactic acid producing Synechocystissp. PCC6803 strains are used to identify the relation between productionrate and enzymatic capacity. The analysis shows that the engineeredcell factories for l-lactic acid are fully limited by themetabolic capacity of the product-forming pathway. We attribute thisto the fact that currently available promoter systems in cyanobacterialack the genetic capacity to a provide sufficient expression in single-genedoses. [ABSTRACT FROM AUTHOR]

Metabolic engineering of microorganisms has become a versatile tool to facilitate production of bulk chemicals, fuels, etc. Accordingly, C02 has been exploited via cyanobacterial metabolism as a sustainable carbon source of biofuel and bioplastic precursors. Here we extended these observations by showing that integration of an Idh gene from Bacillus subtilis (encoding an L-lac-tate dehydrogenase) into the genome of Synechocystis sp. strain PCC6803 leads to L-lactic acid production, a phenotype which is shown to be stable for prolonged batch culturing. Coexpression of a heterologous soluble transhydrogenase leads to an even higher lactate production rate and yield (lactic acid accumulating up to a several-millimolar concentration in the extracellular medium) than those for the single ldh mutant. The expression of a transhydrogenase alone, however, appears to be harmful to the cells, and a mutant carrying such a gene is rapidly outcompeted by a revertant(s) with a wild-type growth phenotype. Furthermore, our results indicate that the introduction of a lactate dehydrogenase rescues this phenotype by preventing the reversion. [ABSTRACT FROM AUTHOR]

The world''s future energy demand calls for a sustainable alternative for the use of fossil fuels, to restrict further global warming. Harvesting solar energy via photosynthesis is one of Nature''s remarkable achievements. Existing technologies exploit this process for energy ‘production’ via processing of, for example, part of plant biomass into ethanol, and of algal biomass into biodiesel. Fortifying photosynthetic organisms with the ability to produce biofuels directly would bypass the need to synthesize all the complex chemicals of ‘biomass’. A promising way to achieve this is to redirect cyanobacterial intermediary metabolism by channeling (Calvin cycle) intermediates into fermentative metabolic pathways. This review describes this approach via the biosynthesis of fermentation end products, like alcohols and hydrogen, driven by solar energy, from water (and CO2). [Copyright &y& Elsevier]

Abstract Dose–response relationships are a general concept for quantitatively describing biological systems across multiple scales, from the molecular to the whole‐cell level. A clinically relevant example is the bacterial growth response to antibiotics, which is routinely characterized by dose–response curves. The shape of the dose–response curve varies drastically between antibiotics and plays a key role in treatment, drug interactions, and resistance evolution. However, the mechanisms shaping the dose–response curve remain largely unclear. Here, we show in Escherichia coli that the distinctively shallow dose–response curve of the antibiotic trimethoprim is caused by a negative growth‐mediated feedback loop: Trimethoprim slows growth, which in turn weakens the effect of this antibiotic. At the molecular level, this feedback is caused by the upregulation of the drug target dihydrofolate reductase (FolA/DHFR). We show that this upregulation is not a specific response to trimethoprim but follows a universal trend line that depends primarily on the growth rate, irrespective of its cause. Rewiring the feedback loop alters the dose–response curve in a predictable manner, which we corroborate using a mathematical model of cellular resource allocation and growth. Our results indicate that growth‐mediated feedback loops may shape drug responses more generally and could be exploited to design evolutionary traps that enable selection against drug resistance.

Exploring the vertical extent of iron sand deposit is challenging as conventional geophysical methods (electrical resistivity, geomagnetic, and seismic refraction) are inappropriate and unsuccessful in delineating the iron sand deposit from the bedrock. Ground-penetrating radar (GPR) offers a solution to the above problem as radar is not affected negatively by the physical properties of iron sand. In the year 2003, a RAMAC’s GPR survey was carried out in the coast of Bayuran in the Regency of Jepara, Central Java to map the distribution of sub-bottom iron sand. The sand is highly magnetic. The survey used 100 MHz antennas. The survey is also complimented by a novel method in determining the electromagnetic (EM) wave velocity of iron sand. Combination of reflection profiling and CMP sounding was deployed. Results of CMP sounding were processed using CMP-semblance analysis that produces the RMS velocity in velocity-time spectra. The RMS velocity is then converted to interval velocity using Dix’s formula and is found to be about 135 mm/ns. Meanwhile, combination of magnetic susceptibility, relative permittivity, and dissipation factors produces radiowaves velocity of iron sand as a function of frequency. The velocities of radiowaves estimated from laboratory match that estimated from CMP analysis.

Introduction: Adherence to COPD management strategies is complex, and it is unclear which intervention may enhance it., Objectives: We aim to evaluate the effectiveness of adherence-enhancing interventions, alone or compared to interventions, for patients with COPD., Methods: This review comprises a component network meta-analysis with a structured narrative synthesis. We searched MEDLINE, Embase, CENTRAL, CINAHL and trial registries on 9 September 2023. We included controlled studies that explored adherence in patients with COPD. Two review authors independently performed the study selection, data extraction and the risk of bias assessment. We involved patients with COPD in developing this systematic review through focus group interviews and displayed the findings in pre-designed logic models., Results: We included 33 studies with 5775 participants. We included 13 studies in the component network meta-analysis that explored adherence. It was mainly assessed through questionnaires. As a continuous outcome, there was a tendency mainly for education (standardised mean difference 1.26, 95% CI 1.13-1.38, very low certainty of evidence) and motivation (mean difference 1.85, 95% CI 1.19-2.50, very low certainty of evidence) to improve adherence. As a dichotomous outcome ( e.g. adherent/non-adherent), we found a possible benefit with education (odds ratio 4.77, 95% CI 2.25-10.14, low certainty of evidence) but not with the other components. We included six studies that reported quality of life in the component network meta-analysis. Again, we found a benefit of education (mean difference -9.70, 95% CI -10.82- -8.57, low certainty of evidence) but not with the other components., Conclusions: Education may improve adherence and quality of life in COPD patients. Patient focus group interviews indicated that interventions that strengthen patients' self-efficacy and help them to achieve individual goals are the most helpful., Competing Interests: Conflict of interest: S. Andreas reports grants from Boehringer, and personal fees from Boehringer, AZ, GSK, Chiesi, Novartis and Menerini, outside the submitted work. T. Friede reports personal fees for statistical consultancies, including data monitoring committees, from Actimed, Aslan, Bayer, Biosense Webster, BMS, CSL Behring, Enanta, Fresenius Kabi, Galapagos, IQVIA, Immunic, Janssen, Kyowa Kirin, LivaNova, Minoryx, Norvartis, PPD, Recardio, Relaxera, Roche, Servier, Viatris, VICO Therapeutics and Vifor, all outside the submitted work. The other authors declare no competing interests., (Copyright ©The authors 2024.)

Both tobacco cessation and low-dose CT screening in at-risk individuals reduce lung cancer-specific and all-cause mortality. As part of a national screening program for the early detection of lung cancer, smoking cessation must be a mandatory part of the counseling given to participants. This increases the cost-benefit effectiveness of the screening program. As part of the initial consultation evidence-based measures for smoking cessation must be offered to smoking participants of the screening program in form of a minimal intervention. If participants do not want to participate in a quit smoking measure they must actively refuse (opt-out rule). The costs of quitting smoking, including the costs of withdrawal-inhibiting medication, have to be fully covered by statutory health insurance for participants in the lung cancer screening program., Competing Interests: Alexander Rupp ist Berater der Firma Sanero Medical GmbH Stuttgart, die eine Internetplattform und eine digitale Gesundheitsanwendung (DiGA) zur Tabakentwöhnung betreibt.Christa Rustler ist Leiterin des Büros des Deutschen Netz rauchfreier Krankenhäuser und Gesundheitseinrichtungen (DNRfK), welches zur Implementierung des „rauchfrei tickets“ Zuwendungen der Bundeszentrale für gesundheitliche Aufklärung (BZgA) erhält.Die anderen Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Almost all e-cigarettes contain flavorings that make the product more attractive. In the evaluation of e-cigarettes on health, flavors have so far played a subordinate role., Method: Selective literature search in PubMed, supplemented by legal regulations on the use of flavors in e-cigarettes., Results: Flavors make it easier to start using e-cigarettes and have a consumption-promoting effect. Deeper inhalation increases nicotine uptake and the absorption of toxic substances from the e-cigarette liquid. For some flavors, pathological effects have been demonstrated in addition to other toxic components of the e-cigarette. To date, no toxicological analyses are available for the vast majority of flavors contained in e-cigarettes., Conclusions: The proven consumption-promoting effect and the health risks that can be extrapolated from preclinical data are significant for the political discussion of a ban on flavors for e-cigarettes, analogous to the ban on flavors in tobacco products already in force., Competing Interests: Klaas Franzen, Stefan Andreas, Wulf Pankow, Wilfried Kunstmann und Reiner Hanewinkel sind ehrenamtlich für das Aktionsbündnis Nichtrauchen tätig. Natascha Sommer erhielt für Ihre Forschung zu E-Zigaretten finanzielle Unterstützung der Balzan-Preis Forschungsgruppe des Deutschen Zentrums für Lungenforschung (DZL) – Erika von Mutius, Klaus F. Rabe, Werner Seeger und Tobias Welte., (Thieme. All rights reserved.)

Tobacco control, psychosocial and medical assistance regarding tobacco cessation is still a hidden potential within the German health care system. So far doctors rarely talk to their patients about their smoking status and physical and psychological benefits of quitting.This paper focusses on recommended current diagnostic and treatment standards, as well as evidence-based methods to address the topic on how to stop smoking and its association with certain diseases such as COPD, lung cancer and COVID-19 infection. The role of e-cigarettes as a cessation tool and its health related risks are critically examined. Consequences and advice how to implement smoking cessation procedures into daily practice are presented., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Competing Interests: SA, DT-HC, JG und FTF haben nichts offenzulegen.

Introduction: Loneliness is a pressing public mental health issue. So far, there has been a paucity of investigations focused on the individual differences modulating this subjective feeling in the face of difficult circumstances, e.g., the COVID-19 pandemic. As such, the present study aimed to investigate the role of mentalization; given that the construct comprises reflection abilities that might be particularly relevant to the pandemic's interpersonal challenges., Methods: A survey representative of the German population was conducted from May to June 2020 (N = 2503). We examined mentalization, operationalized as reflective functioning (RF) and measured using the Mentalization Questionnaire (MZQ), both as a protective factor against loneliness on its own and as a moderator of the association of social isolation with loneliness., Results: Of the overall sample, 822 (32.8 %) individuals reported social isolation. Worse RF was moderately associated with higher levels of loneliness (r = 0.433, p < .001). A linear regression model (controlling for sociodemographic characteristics and general personality pathology) confirmed this positive association, but also indicated an interaction effect of RF and social isolation in the statistical prediction of loneliness. Stratified models showed that RF was a comparatively weaker statistical predictor of loneliness among the socially isolated., Discussion: This representative population study expanded our knowledge about the factors shaping loneliness in the population. RF emerged as a potentially modifiable protective influence. Further research needs to clarify the mechanisms through which it mitigates loneliness., Limitations: The cross-sectional design does not give insight into the temporal association of RF and loneliness., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

E-cigarettes are primarily used by teenagers and young adults. Flavors in e-cigarettes increase their attractiveness and encourage young people and adults to start using them. This exposes young people in particular to the risk of nicotine addiction and various toxic substances from the aerosol of e-cigarettes. There are indications that various flavors in e-cigarettes are harmful to health, although toxicological studies are still lacking for the majority of flavors. There is a need for independent scientific investigations in this area. The scientific societies involved are calling for a ban on flavors in e-cigarettes, a ban on disposable e-cigarettes, effective regulation of the sale of e-cigarettes and effective control and implementation of the provisions for the protection of minors., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Tobacco smoking is widespread in Germany. An increase in the number of teenagers and young adults that smoke has recently been a cause for concern. The high prevalence in Germany is contrasted by inadequate preventive measures compared to international standards. Smoking behavior should always be inquired about and documented in the same way as vital signs. All smokers, regardless of the reason for contact and motivation, should receive short, low-threshold advice, e.g. using the ABC approach (ask, brief advice, cessation). In addition to repeated advice and referral to further services, the use of nicotine replacement or drug therapy is essential for the success of quitting. The combination of long- and short-acting nicotine replacement products doubles the success rate. Electronic nicotine delivery systems are not recommended for smoking cessation., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objective: In recent decades, mentalizing has found its permanent place both in therapeutic practice and in psychotherapy research. Inconsistent results and null results are often found. Therefore, the different methodological approaches should be examined in more detail. A scoping review was conducted to provide an overview of the approaches that measure the patient's mentalizing ability based on therapy sessions or in the course of psychotherapy., Method: For the scoping review, a literature search was conducted in four databases. A total of 3217 records were identified., Results: We included 84 publications from 43 independent studies. Most studies used the Reflective Functioning Scale and applied the scale to therapy sessions or the Adult Attachment Interview. The other identified approaches used a computerized text analysis measure or clinician-report measures. Mostly good psychometric properties of the measures were reported. The Reflective Functioning Scale applied to the Adult Attachment Interview was the only measure that proved to be sensitive to change., Conclusion: More economical variants to the time-consuming Reflective Functioning Scale applied to the Adult Attachment Interview are being developed continuously. In some cases, there is no standardized approach, or the measures are used only sporadically and require further and more comprehensive psychometric evaluations.

The process of implementing early detection of lung cancer with low-dose CT (LDCT) in Germany has gained significant momentum in recent years. It is expected that the ordinance of the Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) on the early detection of lung cancer, which has been commented on by the professional societies, will come into effect by the end of 2023. Based on this regulation, the Federal Joint Committee (G-BA) will set up a program for early lung cancer detection with LDCT in the near future. In this position paper, the specialist societies involved in lung cancer screening present key points for a uniform, structured and quality-assured early detection program for lung cancer in Germany to make a constructive contribution to this process. CITATION FORMAT: · Vogel-Claussen J, Blum TG, Andreas S et al. Position paper on the implementation of a nationally organized program in Germany for the early detection of lung cancer in high-risk populations using low-dose CT screening including the management of screening findings requiring further workup. Fortschr Röntgenstr 2024; 196: DOI 10.1055/a-2178-2846., Competing Interests: T. G. B. gibt eine Forschungsförderung von EU4Health an.J. V.-C. gibt Forschungsförderungen von BMBF, NIH, AstraZeneca, Siemens Healthineers, GlaxoSmithKline und Boehringer Ingelheim sowie Vortrags- oder Beratungshonorare von AstraZeneca, Siemens Healthineers, GlaxoSmithKline und Boehringer Ingelheim an.S. A. gibt eine Mitarbeit im Aktionsbündnis Nichtraucherschutz und in der Task Force Tabakentwöhnung der DGP an.H.-U. K. gibt Forschungsförderungen von Siemens, Philips und Boehringer Ingelheim sowie Vortrags- oder Beratungshonorare von Siemens, Boehringer Ingelheim, Philips, Sanofi und Median an.Alle weiteren Autorinnen und Autoren haben keine potenziellen COI angegeben., (Thieme. All rights reserved.)

After several years of declining tobacco consumption, the number of smokers in Germany is currently stagnating or rising again. The reasons seem to be manifold, e. g. stress caused by the pandemic with social isolation, rising cost of living and war in Europe.With tobacco use still widespread in the German population, evidence-based tobacco cessation is rarely implemented.According to recent studies, e-cigarettes are involved in the pathogenesis of lung disease, cardiac and vascular damage. In addition, their ingredients also have carcinogenic effects. However, clinical studies on long-term use are not yet available.E-cigarettes as a consumer product are not superior to nicotine replacement products and addiction-reducing medications recommended in guidelines. In the therapeutic setting, they are slightly more effective than nicotine replacement products. However, they are usually consumed continuously and thus perpetuate nicotine dependence. Their use increases the risk of relapse to tobacco smoking.Despite the various new approaches, such as Internet-based offerings, app, etc., talks and pharmacotherapy are the gold standard and more effective than any therapy on its own., Competing Interests: PD Dr. med. K. F. Franzen und Prof. Dr.med.W. Pankow sind im Pfizer Advisory Board zur Tabakentwöhnung tätig. Prof. Dr. med. S. Andreas hat keine Interessenkonflikte im Bezug auf diese Publikation., (Thieme. All rights reserved.)

The process of implementing early detection of lung cancer with low-dose CT (LDCT) in Germany has gained significant momentum in recent years. It is expected that the ordinance of the Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) on early detection of lung cancer, which has been commented on by the professional societies, will come into effect by the end of 2023. Based on this regulation, the Federal Joint Committee (G-BA) will set up a program for early lung cancer detection with LDCT in the near future. In this position paper, the specialist societies involved in lung cancer screening present concrete cornerstones for a uniform, structured and quality-assured early detection program for lung cancer in Germany to make a constructive contribution to this process., Competing Interests: T. G. B. gibt eine Forschungsförderung von EU4Health an.J. V.-C. gibt Forschungsförderungen von BMBF, NIH, AstraZeneca, Siemens Healthineers, Glaxo Smith Kline und Boehringer Ingelheim sowie Vortrags- oder Beratungshonorare von AstraZeneca, Siemens Healthineers, GlaxoSmithKline und Boehringer Ingelheim an. S. A. gibt eine Mitarbeit im Aktionsbündnis Nichtraucherschutz und in der Task Force Tabakentwöhnung der DGP an.H.-U. K. gibt Forschungsförderungen von Siemens, Philips und Boehringer Ingelheim sowie Vortrags- oder Beratungshonorare von Siemens, Boehringer Ingelheim, Philips, Sanofi und Median an.Alle weiteren Autorinnen und Autoren haben keine potenziellen COI angegeben., (Thieme. All rights reserved.)

The process of implementing early detection of lung cancer with low-dose CT (LDCT) in Germany has gained significant momentum in recent years. It is expected that the ordinance of the Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) on early detection of lung cancer, which has been commented on by the professional societies, will come into effect by the end of 2023. Based on this regulation, the Federal Joint Committee (G-BA) will set up a program for early lung cancer detection with LDCT in the near future. In this position paper, the specialist societies involved in lung cancer screening present concrete cornerstones for a uniform, structured and quality-assured early detection program for lung cancer in Germany to make a constructive contribution to this process., Competing Interests: T.G.B. gibt eine Forschungsförderung von EU4Health an.J.V.-C. gibt Forschungsförderungen von BMBF, NIH, AstraZeneca, Siemens Healthineers, GlaxoSmithKline und Boehringer Ingelheim sowie Vortrags- oder Beratungshonorare von AstraZeneca, Siemens Healthineers, GlaxoSmithKline und Boehringer Ingelheim an. S.A. gibt eine Mitarbeit im Aktionsbündnis Nichtraucherschutz und in der Task Force Tabakentwöhnung der DGP an.H.-U.K. gibt Forschungsförderungen von Siemens, Philips und Boehringer Ingelheim sowie Vortrags- oder Beratungshonorare von Siemens, Boehringer Ingelheim, Philips, Sanofi und Median an.Alle weiteren Autorinnen und Autoren haben keine potenziellen Interessenkonflikte angegeben., (Thieme. All rights reserved.)

Background: Chronic obstructive pulmonary disease (COPD) is characterised by hyperinflation and expiratory airflow limitation due to long-term exposure to irritants. The variety and complexity of COPD treatment and the possible added comorbidities may make the patients find it difficult to cope with the required medications. That is why supporting patients' adherence is critical because not taking medications correctly increases the risk of complications and creates an additional financial burden. A range of interventions aiming to improve patient adherence were used, and most of them are complex since they involve a mix of elements. Furthermore, despite the variety of available tools, assessing adherence is challenging because clinicians usually do not get a concrete judgement if their patients followed their treatment plan reliably. We aim to evaluate the effectiveness of adherence-enhancing interventions for COPD patients, explore which intervention (component) works for which patients and check the factors influencing the implementation and participant responses., Methods: We will perform a comprehensive literature search (Medline, Embase, Cochrane Library, trial registries) without restrictions on language and publication status, and we will include all controlled studies investigating the effect of adherence-enhancing intervention on patients with COPD. We plan to involve COPD patients in the systematic review development through two patient interviews (one before and one after the systematic review). Two reviewers will perform the screening, data extraction and risk of bias (ROB) assessment. For ROB, we will use ROB 2.0 to assess randomised controlled trials, and ROBINS-I to assess non-randomised studies. We will perform pair-wise random-effects meta-analyses and component network meta-analyses to identify the most effective components and combinations of components. We will use the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence. To determine the degree of complexity, we will use the iCAT&#95;SR checklist, and then, following a logical model, we will group the interventions according to prespecified criteria., Discussion: This systematic review aims to point out the most effective and implementable adherence-enhancing interventions by using methods for synthesising evidence on complex interventions and involving COPD patients all along with the review process., Systematic Review Registration: PROSPERO CRD42022353977., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Endoscopic lung volume reduction (ELVR) with one-way valves produces beneficial outcomes in patients with severe emphysema. Evidence on the efficacy remains unclear in patients with a very low forced expiratory volume in 1 s (FEV 1 ) (≤20% predicted). We aim to compare clinical outcomes of ELVR, in relation to the FEV 1 restriction., Methods: All data originated from the German Lung Emphysema Registry (Lungenemphysem Register), which is a prospective multicentric observational study for patients with severe emphysema after lung volume reduction. Two groups were formed at baseline: FEV 1 ≤20% pred and FEV 1 21-45% pred. Pulmonary function tests (FEV 1 , residual volume, partial pressure of carbon dioxide), training capacity (6-min walk distance (6MWD)), quality of life (modified Medical Research Council dyspnoea scale (mMRC), COPD Assessment Test (CAT), St George's Respiratory Questionnaire (SGRQ)) and adverse events were assessed and compared at baseline and after 3 and 6 months., Results: 33 patients with FEV 1 ≤20% pred and 265 patients with FEV 1 21-45% pred were analysed. After ELVR, an increase in FEV 1 was observed in both groups (both p<0.001). The mMRC and CAT scores, and 6MWD improved in both groups (all p<0.05). The SGRQ score improved significantly in the FEV 1 21-45% pred group, and by trend in the FEV 1 ≤20% pred group. Pneumothorax was the most frequent complication within the first 90 days in both groups (FEV 1 ≤20% pred: 7.7% versus FEV 1 21-45% pred: 22.1%; p=0.624). No deaths occurred in the FEV 1 ≤20% pred group up to 6 months., Conclusion: Our study highlights the potential efficacy of one-way valves, even in patients with very low FEV 1 , as these patients experienced significant improvements in FEV 1 , 6MWD and quality of life. No death was reported, suggesting a good safety profile, even in these high-risk patients., Competing Interests: Conflict of interest: S. Eisenmann reports receiving grants or contracts from DFG, outside the submitted work; consulting fees from Acceleron, AstraZeneca and Sanofi Genzyme, outside the submitted work; payment for expert testimony for Nanovation, outside the submitted work; support for attending meetings and/or travel from Boehringer Ingelheim and Sanofi Genzyme, outside the submitted work. Conflict of interest: M. Witzenrath reports grants or contracts from Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Deutsche Gesellschaft für Pneumologie, European Respiratory Society, Marie Curie Foundation, Else Kröner Fresenius Stiftung, Capnetz Stiftung, Bayer Health Care, Biotest and Pantherna, outside the submitted work; consulting fees from Insmed, Pantherna, Pherecydes, Aptarion, GlaxoSmithKline, Inflarx and Biotest, outside the submitted work; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, Insmed, Chiesi, Novartis, Teva, Actelion, Boehringer Ingelheim, GlaxoSmithKline, Biotest and Bayer Health Care, outside the submitted work; patents issued EPO 12181535.1 (IL-27 for modulation of immune response in acute lung injury), WO/2010/094491 (Means for inhibiting the expression of Ang-2), DE 102020116249.9 (Camostat/Niclosamide cotreatment in SARS-CoV-2 infected human lung cells) and PCT/EP2021/075627 (New medical use of cystic fibrosis transmembrane conductance regulator (CFTR) modulators), outside the submitted work. Conflict of interest: A. Holland reports being a board member of Lungenemphysemregister e.V., outside the submitted work. Conflict of interest: W. Gesierich reports lectures fees from PulmonX GmbH, outside the submitted work. Conflict of interest: R-H. Hübner reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pulmonx, Olympus and AstraZeneca, outside the submitted work; participation on a data safety monitoring board or advisory board for Bento Study (sponsor: IHF GmbH – Institut für Herzinfarktforschung), outside the submitted work; leadership or fiduciary role in other board, society, committee or advocacy group for Head of Lungenemphysem Register e.V., outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Introduction: Between-session processes outside the therapy room and beyond the direct interaction between a therapist and client can play an important role in the psychotherapeutic process and outcome. These processes are called intersession experiences and can be seen as internalized mental representations of therapy and/or therapists. Due to the COVID-19 pandemic, different digital forms of treatment have successfully been implemented and could be relevant even after the end of the COVID-19 pandemic. Therefore, patients' internalized mental representations may become highly relevant in the future., Rationale: The aim of this study was to conceptually delineate the current state of research on internalized mental representations of therapy or therapists in the period between sessions and to provide an overview of the evidence. In addition, we aimed to identify research gaps to provide a baseline for further research., Methods: For this purpose, we conducted a scoping review to obtain a comprehensive overview of the evidence and to identify the relevant research gaps. We searched PsycArticles, Medline, PsycINFO, and PSYNDEX for publications on internalized mental representations., Results: The final sample comprised 30 publications published from 1989 to 2021. Based on the individual study results, it can be assumed that intersession experiences are of central importance for psychotherapeutic treatment. However, the scoping review showed that there was a large gap in knowledge in the research of intersession experiences. All previous research was barely comparable, and therefore, a generalized statement is not possible., Conclusion: Future research should provide sufficient information about relevant aspects, such as the setting, therapists, and patients, as these factors are likely to have a significant impact on the outcome. Furthermore, better measurements for the assessment of these processes should be developed., (© 2023 The Authors. Journal of Clinical Psychology published by Wiley Periodicals Inc.)

Ovarian cancer (OvCa) is the gynaecological disorder with the poorest prognosis due to the fast development of chemoresistance. We sought to connect chemoresistance and cancer cell-derived extracellular vesicles (EV). The mechanisms of how chemoresistance is sustained by EV remained elusive. One potentially contributing factor is A Disintegrin and Metalloprotease 17 (ADAM17)-itself being able to promote chemoresistance and inducing tumour cell proliferation and survival via the Epidermal Growth Factor Receptor (EGFR) pathway by shedding several of its ligands including Amphiregulin (AREG). We now demonstrate that upon chemotherapeutic treatment, proteolytically active ADAM17 is released in association with EV from OvCa cells. In terms of function, we show that patient-derived EV induce AREG shedding and restore chemoresistance in ADAM17-deficient cells. Confirming that ADAM17-containing EV transmit chemoresistance in OvCa, we propose that ADAM17 levels (also on EV) might serve as an indicator for tumour progression and the chemosensitivity status of a given patient., (© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Tobacco smoking is the greatest preventable health risk. The effects are serious, both individually and societal. Nevertheless, the current prevalence of tobacco smokers in Germany is still high at around 35 %. A recent strong increase in actively smoking adolescents (14- to 17-year-olds, current prevalence approx. 16 %) and young adults (18- to 24-year-olds, current prevalence approx. 41 %) is also a cause for concern. About a third of all inpatients continue smoking while being treated. The hospitalization of active smokers in acute and rehabilitation hospitals serves as a "teachable moment" for initiation of cessation offers. An intervention that begins in hospital and continues for at least a month after discharge results in about 40 % additional smokefree patients. It is scientifically well-researched, effective and cost-efficient. After initiation in hospital these measures can be continued via ambulatory cessation programs, rehabilitation facilities, an Internet or telephone service. In Germany, there are structured and quality-assured cessation offers, both for the inpatient and for the outpatient area. The biggest obstacle to broad establishment of such offers is the lack of reimbursement. Two feasible ways to change this would be the remuneration of the existing OPS 9-501 "Multimodal inpatient treatment for smoking cessation" and the establishment of quality contracts according to § 110a SGB V. An expansion of tobacco cessation measures in healthcare facilities would reduce smoking prevalence, associated burden of disease and consecutive costs., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Introduction: The use of humor in psychotherapy is widely considered to improve therapy outcomes and typically depends on context, patient sensitivity, and the therapist's humor style. Different types of humor may impact treatment type, therapeutic alliance, and therapy outcome; however, evidence from psychotherapy sessions on the role of banter has been sparse to date. Therefore, the study aims to examine banter in a secondary analysis of psychotherapy sessions., Method: The sample consisted of 68 depressed outpatients treated with one of three treatment types: psychoanalytic therapy (PA), psychodynamic therapy (PD), and cognitive-behavioral therapy (CBT). Banter and therapeutic alliance were rated for therapy sessions taken from the middle phase of treatment, outcome was assessed at the end of treatment., Results: The main findings were (1) clinical examples of banter in psychotherapy were found in 62 from 68 sessions, (2) significantly more bantering in the main bantering category of facilitation for CBT sessions as compared to other treatment types, (3) facilitative banter as a significant predictor for the positive introject, (4) a significant correlation between bantering and bond between therapist and client. Furthermore, based on these results, psychometric properties of the Klagenfurt Bantering Instrument (KBI) are reported., Conclusion: From a bantering perspective, this study emphasizes the need to consider session context, client response, and sarcastic markers when categorizing negative banter using the KBI., (© 2023 The Authors. Journal of Clinical Psychology published by Wiley Periodicals LLC.)

Treatment concepts in oncology are becoming increasingly personalized and diverse. Successively, changes in standards of care mandate continuous monitoring of patient pathways and clinical outcomes based on large, representative real-world data. The German Cancer Consortium's (DKTK) Clinical Communication Platform (CCP) provides such opportunity. Connecting fourteen university hospital-based cancer centers, the CCP relies on a federated IT-infrastructure sourcing data from facility-based cancer registry units and biobanks. Federated analyses resulted in a cohort of 600,915 patients, out of which 232,991 were incident since 2013 and for which a comprehensive documentation is available. Next to demographic data (i.e., age at diagnosis: 2.0% 0-20 years, 8.3% 21-40 years, 30.9% 41-60 years, 50.1% 61-80 years, 8.8% 81+ years; and gender: 45.2% female, 54.7% male, 0.1% other) and diagnoses (five most frequent tumor origins: 22,523 prostate, 18,409 breast, 15,575 lung, 13,964 skin/malignant melanoma, 9005 brain), the cohort dataset contains information about therapeutic interventions and response assessments and is connected to 287,883 liquid and tissue biosamples. Focusing on diagnoses and therapy-sequences, showcase analyses of diagnosis-specific sub-cohorts (pancreas, larynx, kidney, thyroid gland) demonstrate the analytical opportunities offered by the cohort's data. Due to its data granularity and size, the cohort is a potential catalyst for translational cancer research. It provides rapid access to comprehensive patient groups and may improve the understanding of the clinical course of various (even rare) malignancies. Therefore, the cohort may serve as a decisions-making tool for clinical trial design and contributes to the evaluation of scientific findings under real-world conditions., (© 2023. The Author(s).)

Objective: This empirical study undertakes a categorization of the core concept of Control Mastery Theory: mostly unconscious testing of pathogenic beliefs that patients exhibit in relating to their therapist to work on their problems. The focus lays on latent meanings of manifest tests., Method: We qualitatively analyze transcripts of 172 psychotherapy sessions with 23 patients for sequences in which significant patient-therapist interactions occur, and systematize identified tests into thematic categories based on what tests intent to achieve (ICC = .68). Guided by theory, the analysis is attending to complexity, individuality, and the unconscious., Results: Tests circle around striving for independence, deserving/self-worth, acceptance, and entitlement. Individual tests have various underlying meanings, are interrelated, and may be multidimensional., Conclusion: Meanings of tests must be confirmed within the psychotherapeutic process. Incorporating the treating clinician thus seems important.

Tobacco dependence is a common comorbidity in patients with COPD (Chronic Obstructive Pulmonary Disease) that negatively affects the course of the disease. However, clinically relevant improvement in COPD can only be achieved by complete and permanent abstinence. Therefore, abstinence from tobacco use is a central therapeutic concept in smoking patients with COPD and requires specific and targeted treatment.After detailed documentation of smoking behaviour and motivational counseling outlining the risks of smoking, all such patients shall be offered a structured therapy for tobacco cessation. There is high-quality evidence for the effectiveness of a combination therapy of behavioral therapy and medication (to treat the withdrawal syndrome). Due to insufficient data, there is currently no recommendation for the use of e-cigarettes as a primary option for a cessation attempt.Smoking is the most important cause of COPD. Smoking cessation is the most effective and cost-efficient single intervention to reduce the risk of developing and progressing COPD., Competing Interests: SA erhielt Forschungsförderung von Boehringer Ingelheim und Honorar für Referententätigkeit von Boehringer Ingelheim, Novartis, AstraZeneca, GSK, Chiesi, Merini. SA ist Leiter der Task Force Tabakentwöhnung der DGP und Mitglied des ABNR.DK erhielt Forschungsförderung vom Bundesministerium für Gesundheit für die Durchführung der Deutschen Befragung zum Rauchverhalten (DEBRA; DRKS00017157 und DRKS00028054) und für die ABC-II-Studie (RCT zum Training von Hausärzten in der leitliniengerechten Kurzberatung zur Tabakentwöhnung; DRKS00012786).AB erklärt: Förderung durch die Bundeszentrale für gesundheitliche Aufklärung, eigenes Tabakentwöhnungsprogramm (Nichtraucher in sechs Wochen). Mitglied im Vorstand des Wissenschaftlichen Aktionskreises Tabakentwöhnung (WAT) e. V. und der Deutschen Gesellschaft für Suchtforschung und Suchttherapie (DG-Sucht) e. V.AH hielt Vorträge für Orion Pharma.SM erklärt: Pfizer (Vortragshonorar + Beratung); Johnson + Johnson (Honorartätigkeit Workshop + Advisory Board); Leitung Raucherambulanz Chemnitz; Wissenschaftlicher Arbeitskreis Tabakentwöhnung; Mitarbeit S3 LL Alkohol und Tabak.DN erhielt Forschungsunterstützung für Forschungsprojekte des Instituts von EU, DFG, BMBF, BMG, DGUV, BGW, Verwaltungs-BG, Bundesarbeitsministerium, Bayerischen Ministerien, Industrie (MAN, FMG, Siemens, Audi), Versicherungen, ADAC/ÖAMTC, Kliniken, Erzbischöfliches Ordinariat, Caritas. DN erhielt Vortragshonorare von Bristol MyersSquibb, Berlin Chemie, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, Novartis, Hexal, Lilly. DN ist Mitglied eines Advisory Boards von Pfizer zur Rauchentwöhnung. DN ist Vertreter der Deutschen Gesellschaft für Arbeitsmedizin und Umweltmedizin im Aktionsbündnis Nichtrauchen (ABNR).KS erhielt Forschungsförderung von der Deutschen Rentenversicherung Bayern Süd und Honorare für Referententätigkeit von AstraZeneca, GSK, Chiesi, Sanofi Genzyme und Berlin-Chemie.HW erklärt, während der letzten 3 Jahre keine wirtschaftlichen oder persönlichen Verbindungen im oben genannten Sinne zu haben.SS begleitet im Rahmen ihrer Tätigkeit beim ÄZQ die Erstellung von Leitlinien methodisch und organisatorisch., (Thieme. All rights reserved.)

Endometrial cancer (EC) is the most common gynaecological malignancy with increasing incidence in developed countries. As gold standard, hysteroscopy confirms only 30% of suspected ECs. The detection of EC cells in the vagina by fluorescence in situ hybridization (FISH) after a smear test could reduce invasive procedures in the future. Using array-based comparative genome hybridization (aCGH) on 65 endometrial carcinomas, most frequently imbalanced regions of the tumour genome were identified. Bacterial artificial chromosomes were used to generate FISH-probes homologue to these human regions. The FISH test was hybridized on swabs specimens collected from the vaginal cavity. Samples from six patients without EC were selected as a negative control and on 13 patients with known EC as a positive control. To distinguish between benign and EC cases, the cut-off value has been defined. A first validation of this EC-FISH Test was performed with swabs from 41 patients with suspected EC. The most common genomic imbalances in EC are around the CTNNB1, FBXW7 and APC genes. The cut-off is defined at 32% of analysed cells without diploid signal pattern. This differs significantly between the positive and negative controls (p < 0.001). In a first validation cohort of 41 patients with suspected EC, the EC-FISH Test distinguishes patients with and without EC with a sensitivity of 91% and a specificity of 83%. The negative predictive value is 96%. This is the first report of a non-invasive EC-FISH Test to predict EC in women with suspected EC., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)