Computational Screening of Hydrophobic Zeolites for the Removal of Emerging Organic Contaminants from Water.

The pollution of water resources by pharmaceuticals and agents of personal care products (PPCPs) poses an increasingly pressing issue that has received considerable attention from scientists and government agencies alike. Hydrophobic zeolites can serve as selective adsorbents to remove these contaminants from aqueous solution. So far, the adsorption of PPCPs in zeolites has often been investigated in case studies focusing on a small number of contaminants and one or a few zeolites. We present a computational screening approach to investigate the interaction of 53 PPCPs with 14 all-silica zeolites, aiming at a more comprehensive understanding of factors that are beneficial for a strong host-guest interaction and thus an efficient adsorption. The systems are modelled on the classical force field level of theory, allowing for the efficient computational treatment of a large number of PPCP-zeolite combinations and evaluated in terms of the interaction energy between PPCP and zeolite framework. For selected PPCP-zeolite combinations additional Free Energy Perturbation simulations are employed to compute Free Energies of Transfer between the aqueous phase and the adsorbed state. These results can serve as a starting point for experimental studies of relevant PPCP-zeolite combination or more in-depth theoretical investigations.

Role of Ethics in Developing AI-Based Applications in Medicine: Insights From Expert Interviews and Discussion of Implications.

BACKGROUND: The integration of artificial intelligence (AI)-based applications in the medical field has increased significantly, offering potential improvements in patient care and diagnostics. However, alongside these advancements, there is growing concern about ethical considerations, such as bias, informed consent, and trust in the development of these technologies. OBJECTIVE: This study aims to assess the role of ethics in the development of AI-based applications in medicine. Furthermore, this study focuses on the potential consequences of neglecting ethical considerations in AI development, particularly their impact on patients and physicians. METHODS: Qualitative content analysis was used to analyze the responses from expert interviews. Experts were selected based on their involvement in the research or practical development of AI-based applications in medicine for at least 5 years, leading to the inclusion of 7 experts in the study. RESULTS: The analysis revealed 3 main categories and 7 subcategories reflecting a wide range of views on the role of ethics in AI development. This variance underscores the subjectivity and complexity of integrating ethics into the development of AI in medicine. Although some experts view ethics as fundamental, others prioritize performance and efficiency, with some perceiving ethics as potential obstacles to technological progress. This dichotomy of perspectives clearly emphasizes the subjectivity and complexity surrounding the role of ethics in AI development, reflecting the inherent multifaceted nature of this issue. CONCLUSIONS: Despite the methodological limitations impacting the generalizability of the results, this study underscores the critical importance of consistent and integrated ethical considerations in AI development for medical applications. It advocates further research into effective strategies for ethical AI development, emphasizing the need for transparent and responsible practices, consideration of diverse data sources, physician training, and the establishment of comprehensive ethical and legal frameworks.

Thermal behaviors during lithium diffusion in Li0.4WO3 bronze studied by elastic and quasi-elastic neutron scattering.

Polycrystalline Li0.4WO3 bronze has been synthesized by solid state reaction carried out in a silica tube at 10-7 MPa and 973 K. The sample is characterized by temperature-dependent neutron elastic and quasielastic scatterings. The room-temperature neutron powder data Rietveld refinement confirmed the space group Im3̄ along with lithium occupancy found predominantly at the 6b crystallographic site. Upon increasing temperature above 300 K lithium at 6b site decreases and at 2a site increases, suggesting Li+ cation diffusion between these two sites demonstrated by quasielastic neutron scattering as well. The lattice thermal expansion anomaly is observed between 380 K and 450 K, which is explained in terms of lithium dynamic disorder (non-equilibrium) as complemented by elastic and quasielastic neutron scatterings. DFT calculations with different lithium distributions at two different crystallographic sites guide to understand the lattice expansion anomaly. The lattice thermal expansion is modeled using Grüneisen first-order approximation, where the Debye-Einstein-Anharmonicity approach provides the temperature-dependent vibrational energy. The DFT-calculated phonon density of states and bulk modulus help extract the characteristic Debye and Einstein frequencies.

Exploring physical activity preferences and motivation in long-term cardiac prevention: An Austrian cross-sectional survey.

Cardiac rehabilitation (CR) patients often do not sustain physical activity (PA) behaviour in the long run, once they progress into a self-management stage of secondary prevention. This study aimed to explore former CR patients' PA preferences, determinants (i.e., influencing factors) and motivation for sustained PA engagement. We conducted a cross-sectional multi-centre survey using an original questionnaire based on prior qualitative interviews with cardiac patients. Five CR centres in Austria posted 500 questionnaires to former CR patients who had completed CR approximately three years prior, and 117 patients (23%) responded. Descriptive analysis was used to analyse closed-ended questions, and self-determination theory (SDT) was applied as a qualitative framework to analyse open-ended questions concerning motivation for PA engagement. Patients were generally physically active, but the majority (75.3%) did not fulfil the World Health Organisation's recommendations for aerobic PA and muscle strengthening. Most patients preferred being physically active outdoors (70%), engaging in aerobic-related (95%), individual and non-competitive exercises, with cycling (52%), walking (32%) and hiking (25%) among the most popular activities. Main determinants of PA were health, pain and motivation for 80%, 68%, 67% of patients, respectively. A subset of patients (77%) expanded on their motivations behind PA. According to SDT, most reasons (90%) were regulated by autonomous motivation (either extrinsically autonomously-regulated or intrinsic motivation) and stemmed mostly from health-related goals (e.g., fitness, general health, weight control), future quality-of-life aspirations (e.g., self-sufficiency in old age, presence for loved ones, preserving mobility) and enjoyment of PA. Patients' responses underscore the importance of promoting not only general PA, but also muscle strengthening training in CR interventions to maximise optimal health benefits. Our data further suggest that interventions which are aligned to patients' health goals and foster autonomous motivation may be particularly beneficial in increasing adherence to PA in the long-term.

Appropriateness of Antibiotic Prescribing in US Emergency Department Visits, 2016-2021.

In this national analysis of US emergency department visits with antibiotic prescribing during 2016-2021, 27.6% of visits resulted in inappropriate antibiotic prescribing: 14.9% had diagnosis codes plausibly antibiotic-related (eg, acute bronchitis), suggesting actual inappropriate prescribing, and 12.6% had diagnosis codes not plausibly antibiotic-related (eg, hypertension), suggesting poor coding quality.

Utilization of Mental Health Provision, Epistemic Stance and Comorbid Psychopathology of Individuals with Complex Post-Traumatic Stress Disorders (CPTSD)-Results from a Representative German Observational Study.

Background: Complex post-traumatic stress disorder (CPTSD) is a severely debilitating recently added symptom cluster in the International Classification of Diseases (ICD-11). So far, only limited information on mental health treatment-uptake and -satisfaction of individuals with CPTSD is available. The aim of this study is to investigate these aspects in a representative sample of the German general population. Methods: Participants completed the International Trauma Questionnaire (ITQ) to identify participants with CPTSD, as well as questionnaires on mental health treatment uptake and satisfaction, adverse childhood experiences, anxiety, depression, working ability, personality functioning, and epistemic trust. Results: Of the included n = 1918 participants, n = 29 (1.5%) fulfilled the criteria for CPTSD. Participants with CPTSD had received mental health treatment significantly more often than participants with PTSD or depression (65.5% vs. 58.8% vs. 31.6%; p = 0.031) but reported significantly less symptom improvement (52.9% vs. 78.0% vs. 80.0%; p = 0.008). Lower levels of epistemic trust were associated with higher CPTSD symptoms (p < 0.001). Conclusions: Our study shows that while the vast majority of individuals with CPTSD had received mental health treatment, subjective symptom improvement rates are not satisfactory. CPTSD was associated with a broad number of comorbidities and impairments in functioning. Lower levels of epistemic trust may partially explain worse treatment outcomes.

Prevalence and Risk Factors of Fatigue in Adults with Stage 3 and 4 CKD: Findings from NHANES 2007-2012.

BACKGROUND: Fatigue is a devastating symptom experienced by adults with chronic kidney disease (CKD), but less is known about the prevalence of fatigue and factors associated with fatigue in a general population of adults with CKD. Therefore, we examined the prevalence of fatigue and identified factors associated with fatigue amongst a national cohort of US adults with CKD. METHODS: We utilized cross-sectional data from 1,079 adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2012 and included participants aged 18 and over with CKD Stage 3 and 4 (eGFR between 15 and 60 ml/min/1.73m2) who had available data evaluating fatigue. Unadjusted and adjusted logistic regression models were used to evaluate the odds of having fatigue in the context of physiological, sociodemographic, psychological, and behavioral factors. RESULTS: We estimated that 48% of those with CKD had fatigue. Among the risk factors examined, the factors with the strongest evidence of association in multivariable analyses were female sex (OR 1.49, 95% CI: 1.02, 2.17), pain (OR 2.49, 95% CI: 1.57, 3.93), poor mental health (OR 1.97, 95% CI: 1.05, 3.72), anxiety (OR 1.95, 95% CI: 1.14, 3.34), and depressive symptoms (OR 2.58, 95% CI: 1.17, 5.66). CONCLUSIONS: Fatigue is a common symptom experienced by adults with CKD in the US. Physiological, sociodemographic, psychological, and behavioral factors are associated with fatigue, with psychological factors being most strongly associated. Future work is needed to identify interventions to mitigate fatigue and risk factors for fatigue in adults with CKD.

Correlation of TRPA1 RNAscope and Agonist Responses.

The TRPA1 ion channel is a sensitive detector of reactive chemicals, found primarily on sensory neurons. The phenotype exhibited by mice lacking TRPA1 suggests its potential as a target for pharmacological intervention. Antibody-based detection for distribution analysis is a standard technique. In the case of TRPA1, however, there is no antibody with a plausible validation in knockout animals or functional studies, but many that have failed in this regard. To this end we employed the single molecule in situ hybridization technique RNAscope on sensory neurons immediately after detection of calcium responses to the TRPA1 agonist allyl isothiocyanate. There is a clearly positive correlation between TRPA1 calcium imaging and RNAscope detection (R = 0.43), although less than what might have been expected. Thus, the technique of choice should be carefully considered to suit the research question. The marginal correlation between TRPV1 RNAscope and the specific agonist capsaicin indicates that such validation is advisable for every RNAscope target. Given the recent description of a long-awaited TRPA1 reporter mouse, TRPA1 RNAscope detection might still have its use cases, for detection of RNA at particular sites, for example, defined structurally or by other molecular markers.

Mid-term results of autologous matrix-induced chondrogenesis for large chondral defects in hips with femoroacetabular impingement syndrome.

Aims: The purpose of this study was to evaluate the mid-term outcomes of autologous matrix-induced chondrogenesis (AMIC) for the treatment of larger cartilage lesions and deformity correction in hips suffering from symptomatic femoroacetabular impingement (FAI). Methods: This single-centre study focused on a cohort of 24 patients with cam- or pincer-type FAI, full-thickness femoral or acetabular chondral lesions, or osteochondral lesions ≥ 2 cm2, who underwent surgical hip dislocation for FAI correction in combination with AMIC between March 2009 and February 2016. Baseline data were retrospectively obtained from patient files. Mid-term outcomes were prospectively collected at a follow-up in 2020: cartilage repair tissue quality was evaluated by MRI using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. Patient-reported outcome measures (PROMs) included the Oxford Hip Score (OHS) and Core Outcome Measure Index (COMI). Clinical examination included range of motion, impingement tests, and pain. Results: A total of 12 hips from 11 patients were included (ten males, one female, mean age 26.8 years (SD 5.0), mean follow-up 6.2 years (SD 5.2 months)). The mean postoperative MOCART score was 66.3 (SD 16.3). None of the patients required conversion to total hip arthroplasty. Two patients had anterior impingement. External hip rotation was moderately limited in four patients. There was a correlation between MOCART and follow-up time (rs = -0.61; p = 0.035), but not with initial cartilage damage, age, BMI, or imaging time delay before surgery. PROMs improved significantly: OHS from 37.4 to 42.7 (p = 0.014) and COMI from 4.1 to 1.6 (p = 0.025). There was no correlation between MOCART and PROMs. Conclusion: Based on the reported mid-term results, we consider AMIC as an encouraging treatment option for large cartilage lesions of the hip. Nonetheless, the clinical evidence of AMIC in FAI patients remains to be determined, ideally in the context of randomized controlled trials.

Single molecule studies of dynamic platelet interactions with endothelial cells.

A biotechnological platform consisting of two-color 3D super-resolution readout and a microfluidic system was developed to investigate platelet interaction with a layer of perfused endothelial cells under flow conditions. Platelet activation has been confirmed via CD62P clustering on the membrane and mitochondrial morphology of ECs at the single cell level were examined using 3D two-color single-molecule localization microscopy and classified applying machine learning. To compare binding of activated platelets to intact or stressed ECs, a femtosecond laser was used to induced damage to single ECs within the perfused endothelial layer. We observed that activated platelets bound to the perfused ECs layer preferentially in the proximity to single stressed ECs. Platelets activated under flow were ∼6 times larger compared to activated ones under static conditions. The CD62P expression indicated more CD62P proteins on membrane of dynamically activated platelets, with a tendency to higher densities at the platelet/EC interface. Platelets activated under static conditions showed a less pronounced CD62P top/bottom asymmetry. The clustering of CD62P in the platelet membrane differs depending on the activation conditions. Our results confirm that nanoscopic analysis using two-color 3D super-resolution technology can be used to assess platelet interaction with a stressed endothelium under dynamic conditions.

Changes in the Appropriateness of US Outpatient Antibiotic Prescribing After the Coronavirus Disease 2019 Outbreak: An Interrupted Time Series Analysis of 2016-2021 Data.

BACKGROUND: No national study has evaluated changes in the appropriateness of US outpatient antibiotic prescribing across all conditions and age groups after the coronavirus disease 2019 (COVID-19) outbreak in March 2020. METHODS: This was an interrupted time series analysis of Optum's de-identified Clinformatics Data Mart Database, a national commercial and Medicare Advantage claims database. Analyses included prescriptions for antibiotics dispensed to children and adults enrolled during each month during 2017-2021. For each prescription, we applied our previously developed antibiotic appropriateness classification scheme to International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes on medical claims occurring on or during the 3 days prior to dispensing. Outcomes included the monthly proportion of antibiotic prescriptions that were inappropriate and the monthly proportion of enrollees with ≥1 inappropriate prescription. Using segmented regression models, we assessed for level and slope changes in outcomes in March 2020. RESULTS: Analyses included 37 566 581 enrollees, of whom 19 154 059 (51.0%) were female. The proportion of enrollees with ≥1 inappropriate prescription decreased in March 2020 (level decrease: -0.80 percentage points [95% confidence interval {CI}, -1.09% to -.51%]) and subsequently increased (slope increase: 0.02 percentage points per month [95% CI, .01%-.03%]), partly because overall antibiotic dispensing rebounded and partly because the proportion of antibiotic prescriptions that were inappropriate increased (slope increase: 0.11 percentage points per month [95% CI, .04%-.18%]). In December 2021, the proportion of enrollees with ≥1 inappropriate prescription equaled the corresponding proportion in December 2019. CONCLUSIONS: Despite an initial decline, the proportion of enrollees exposed to inappropriate antibiotics returned to baseline levels by December 2021. Findings underscore the continued importance of outpatient antibiotic stewardship initiatives.

Prevalence of Inappropriate Antibiotic Prescribing with or without a Plausible Antibiotic Indication among Safety-Net and Non-Safety Net Populations.

BACKGROUND: Clinicians can prescribe antibiotics inappropriately without coding the indication for antibiotics. Whether the prevalence of inappropriate antibiotic prescribing with or without a plausible indication differs between safety-net and non-safety-net populations is unknown. OBJECTIVE: To assess differences in inappropriate antibiotic prescribing with or without a plausible indication between safety-net and non-safety net populations. DESIGN: Cross-sectional. PARTICIPANTS: Office visits in the 2016, 2018, 2019 National Ambulatory Medical Care Survey with ≥ 1 antibiotic prescription among children (0-17 years) and adults (18-64 years). MAIN MEASURES: Inappropriate antibiotic prescribing with a plausible indication (visits with infection-related diagnosis codes that do not warrant antibiotics, e.g., acute bronchitis); inappropriate prescribing without a plausible indication (visits with codes that are not antibiotic indications, e.g., hypertension). By age group, we used linear regression to assess differences between safety-net (public/no insurance) and non-safety net populations (privately insured), controlling for patient and visit characteristics. KEY RESULTS: Analyses included 67,065,108 and 122,731,809 weighted visits for children and adults, respectively. Among visits for children in the safety-net and non-safety populations, the prevalence of inappropriate antibiotic prescribing with a plausible indication was 11.7% and 22.0% (adjusted difference: -8.0%, 95% CI: -17.1%, 1.0%); the prevalence of inappropriate prescribing without a plausible indication was 11.8% and 8.6% (adjusted difference: -2.0%, 95% CI: -4.6%, 0.6%). Among visits for adults in the safety-net and non-safety populations, the prevalence of inappropriate antibiotic prescribing with a plausible indication was 12.1% and 14.3% (adjusted difference: -0.1%, 95% CI -9.4%, 9.1%); the prevalence of inappropriate prescribing without a plausible indication was 48.2% and 32.3% (adjusted difference: 12.5%, 95% CI: 3.6%, 21.4%). CONCLUSIONS: Inappropriate antibiotic prescribing with or without a plausible antibiotic indication is common in all populations, highlighting the importance of broad-based antibiotic stewardship initiatives. However, targeted initiatives focused on improving coding quality in adult safety-net settings may be warranted.

Arthropods as Vectors of Grapevine Trunk Disease Pathogens: Quantification of Phaeomoniella chlamydospora on Arthropods and Mycobiome Analysis of Earwig Exoskeletons.

Viticulture worldwide is challenged by grapevine trunk diseases (GTDs). Involvement of arthropods in the dissemination process of GTD pathogens, notably esca pathogens, is indicated after detection of associated pathogens on arthropod exoskeletons, and demonstration of transmission under artificial conditions. The present study is the first to quantify spore loads via qPCR of the esca-relevant pathogen Phaeomoniella chlamydospora on arthropods collected in German vineyards, i.e., European earwigs (Forficula auricularia), ants (Formicidae), and two species of jumping spiders (Marpissa muscosa and Synageles venator). Quantification of spore loads showed acquisition on exoskeletons, but most arthropods carried only low amounts. The mycobiome on earwig exoskeletons was described for the first time to reveal involvement of earwigs in the dispersal of GTDs in general. Metabarcoding data support the potential risk of earwigs as vectors for predominantly Pa. chlamydospora and possibly Eutypa lata (causative agent of Eutypa dieback), as respective operational taxonomical unit (OTU) assigned genera had relative abundances of 6.6% and 2.8% in total reads, even though with great variation between samples. Seven further GTD-related genera were present at a very low level. As various factors influence the successful transmission of GTD pathogens, we hypothesize that arthropods might irregularly act as direct vectors. Our results highlight the importance of minimizing and protecting pruning wounds in the field.

Female Patients Show a Larger Reduction in Suicidal Ideation in Inpatient Addiction Treatment Than Male Patients: Results of a Single-Center Observational Study.

Background: Substance use disorders (SUD) are prevalent disorders worldwide. Among other associated health problems, patients with SUD are at an increased risk of dying of suicide, with females displaying an even higher risk than males. Therefore, the aim of this study was to conduct a gender-sensitive evaluation of changes in suicidal ideation during multimodal inpatient treatment at a hospital facility specialized in treating addiction. Methods: A total of 694 patients (68.2% male) completed routine assessment including suicidal ideation, abstinence confidence, impulsivity, emotion regulation, self-efficacy and autonomy and joy both before (T1) and at the end (T2) of treatment. Mean changes were evaluated with repeated measures MANOVAs. Results: Before treatment, a total of n=127 (18.3%) of the respondents reported suicidal ideation, which was reduced to n=72 (10.4%) by the end of treatment. Among female patients, the change in reported suicidal ideation compared from T1 to T2 (21.7% vs 7.7%) was significantly higher than among male patients (T1: 16.7%%, T2: 11.6%; p=0.040). Generally, females reported worse symptoms scores and slightly higher numbers of suicidal thoughts at baseline (effect sizes ranging from η²=.008 - 0.044). While both genders significantly profited from the treatment, female patients generally showed larger improvements than male. Discussion: Our study underscores the beneficial effect of addiction-specialized inpatient treatment on suicidal ideation. Additionally, we found a substantial gender effect: while female patients generally were more distressed before treatment, they also reported higher symptom reduction during the treatment. This result highlights the need to perform more gender-sensitive research and develop more gender-sensitive treatment programs.

Depressive Symptoms, Antidepressants, and Clinical Outcomes in Chronic Kidney Disease: Findings from the CRIC Study.

Rationale & Objective: The extent to which depression affects the progression of chronic kidney disease (CKD) and leads to adverse clinical outcomes remains inadequately understood. We examined the association of depressive symptoms (DS) and antidepressant medication use on clinical outcomes in 4,839 adults with nondialysis CKD. Study Design: Observational cohort study. Setting and Participants: Adults with mild to moderate CKD who participated in the multicenter Chronic Renal Insufficiency Cohort Study (CRIC). Exposure: The Beck Depression Inventory (BDI) was used to quantify DS. Antidepressant use was identified from medication bottles and prescription lists. Individual effects of DS and antidepressants were examined along with categorization as follows: (1) BDI <11 and no antidepressant use, (2) BDI <11 with antidepressant use, (3) BDI ≥11 and no antidepressant use, and (4) BDI ≥11 with antidepressant use. Outcomes: CKD progression, incident cardiovascular disease composite, all-cause hospitalizations, and mortality. Analytic Approach: Cox regression models were fitted for outcomes of CKD progression, incident cardiovascular disease, and all-cause mortality, whereas hospitalizations used Poisson regression. Results: At baseline, 27.3% of participants had elevated DS, and 19.7% used antidepressants. Elevated DS at baseline were associated with significantly greater risk for an incident cardiovascular disease event, hospitalization, and all-cause mortality, but not CKD progression, adjusted for antidepressants. Antidepressant use was associated with higher risk for all-cause mortality and hospitalizations, after adjusting for DS. Compared to participants without elevated DS and not using antidepressants, the remaining groups (BDI <11 with antidepressants; BDI ≥11 and no antidepressants; BDI ≥11 with antidepressants) showed higher risks of hospitalization and all-cause mortality. Limitations: Inability to infer causality among depressive symptoms, antidepressants, and outcomes. Additionally, the absence of nonpharmacological data, and required exploration of generalizability and alternative analytical approaches. Conclusions: Elevated DS increased adverse outcome risk in nondialysis CKD, unattenuated by antidepressants. Additionally, investigation into the utilization and counterproductivity of antidepressants in this population is warranted.

We analyzed data from 4,839 nondialysis chronic kidney disease (CKD) patients in the Chronic Renal Insufficiency Cohort Study to explore how depression and antidepressants affect CKD-related outcomes. Using the Beck Depression Inventory (BDI), we assessed depressive symptoms (DS) and identified antidepressant use through medication records. Outcomes included CKD progression, cardiovascular events, hospitalizations, and mortality. Elevated DS at baseline raised the risk of cardiovascular events, hospitalizations, and mortality, regardless of antidepressant use. Antidepressant use alone was associated with higher mortality and hospitalization risks. In comparison to those without elevated DS and no antidepressant use, all other groups faced increased hospitalization and mortality risks. Elevated DS posed a significant risk to nondialysis CKD patients, and antidepressants did not mitigate this risk.

Studying the adsorption of emerging organic contaminants in zeolites with dispersion-corrected density functional theory calculations: From numbers to recommendations.

Adsorption energies obtained from dispersion-corrected density functional theory (DFT) calculations show a considerable dependence on the choice of exchange-correlation functional and dispersion correction. A number of investigations have employed different approaches to compute adsorption energies of small molecules in zeolites, using reference values from high-level calculations and/or experiments. Such comparative studies are lacking for larger functional organic molecules such as pharmaceuticals or personal care products, despite their potential relevance for applications, e. g., in contaminant removal or drug delivery. The present study aims to fill this gap by comparing adsorption energies and, for selected cases, equilibrium structures of emerging organic contaminants adsorbed in MOR- and FAU-type all-silica zeolites. A total of 13 dispersion-corrected DFT approaches are compared, including methods using a pairwise dispersion correction as well as non-local van der Waals density functionals. While absolute values of adsorption energies vary widely, qualitative trends across the set of zeolite-guest combinations are not strongly dependent on the choice of functional. For selected cluster models, DFT adsorption energies are compared to reference values from coupled cluster (DLPNO-CCSD(T)) calculations. Although all DFT approaches deliver systematically more negative adsorption energies than the coupled cluster reference, this tendency is least pronounced for the rev-vdW-DF2 functional.

Prognostic significance of circulating tumor cells and tumor related transcripts in small cell lung cancer: A step further to clinical implementation.

Small-cell lung cancer (SCLC) is a fatal disease with limited treatment options. Circulating tumor cells (CTCs) in liquid biopsy samples may serve as predictive and prognostic biomarkers; but the analysis of CTCs is still challenging. By using microfluidic or density gradient CTC enrichment in combination with immunofluorescent (IF) staining or qPCR of CTC-related transcripts, we achieved a 60.8% to 88.0% positivity in SCLC blood samples. Epithelial and neuroendocrine transcripts including the druggable target DLL3 were associated with shorter overall survival (OS), indicating the clinical value of these markers in terms of differential diagnosis and treatment decisions. High CTC counts and the presence of CTC duplets detected by IF staining were prognostic for OS, and thus may serve as indicators of disease progression or therapy failure. In patient samples with high CTC load detected by IF staining, a concordance of the transcripts positivity in circulating free plasma RNA and CTCs was observed. Our data emphasize the role of CTCs and CTC-related transcripts and underline the clinical value of liquid biopsy analysis in SCLC.

Impact of production methods and storage conditions on extracellular vesicles in packed red blood cells and platelet concentrates.

The use of blood and blood products can be life-saving, but there are also certain risks associated with their administration and use. Packed red blood cells (pRBCs) and platelet concentrates are the most commonly used blood products in transfusion medicine to treat anemia or acute and chronic bleeding disorders, respectively. During the production and storage of blood products, red blood cells and platelets release extracellular vesicles (EVs) as a result of the storage lesion, which may affect product quality. EVs are subcellular structures enclosed by a lipid bilayer and originate from the endosomal system or from the plasma membrane. They play a pivotal role in intercellular communication and are emerging as important regulators of inflammation and coagulation. Their cargo and their functional characteristics depend on the cell type from which they originate, as well as on their microenvironment, influencing their capacity to promote coagulation and inflammatory responses. Hence, the potential involvement of EVs in transfusion-related adverse events is increasingly recognized and studied. Here, we review the knowledge regarding the effect of production and storage conditions of pRBCs and platelet concentrates on the release of EVs. In this context, the mode of processing and anticoagulation, the influence of additive solutions and leukoreduction, as well as the storage duration will be addressed, and we discuss potential implications of EVs for the clinical outcome of transfusion.

Association of Four Interleukin-8 Polymorphisms (-251 A>T, +781 C>T, +1633 C>T, +2767 A>T) with Ovarian Cancer Risk: Focus on Menopausal Status and Endometriosis-Related Subtypes.

Interleukin-8 (IL-8) is involved in the regulation of inflammatory processes and carcinogenesis. Single-nucleotide polymorphisms (SNPs) within the IL-8 gene have been shown to alter the risks of lung, gastric, or hepatocellular carcinomas. To date, only one study examined the role of IL-8 SNPs in ovarian cancer (OC), suggesting an association between two IL-8 SNPs and OC risk. In this study, we investigated four common IL-8 SNPs, rs4073 (-251 A>T), rs2227306 (+781 C>T), rs2227543 (+1633 C>T), and rs1126647 (+2767 A>T), using the restriction fragment length polymorphism (PCR-RFLP) technique. Our study included a cohort of 413 women of Central European descent, consisting of 200 OC patients and 213 healthy controls. The most common (73.5%) histological type was high-grade serous OC (HGSOC), whereas 28/200 (14%) patients had endometriosis-related (clear cell or endometrioid) OC subtypes (EROC). In postmenopausal women, three of the four investigated SNPs, rs4073 (-251 A>T), rs2227306 (+781 C>T), and rs2227543 (+1633 C>T), were associated with OC risk. Furthermore, we are the first to report a significant relationship between the T allele or TT genotype of SNP rs1126647 (+2767 A>T) and the EROC subtype (p = 0.02 in the co-dominant model). The TT homozygotes were found more than twice as often in EROC compared to other OC subtypes (39% vs. 19%, p = 0.015). None of the examined SNPs appeared to influence OC risk in premenopausal women, nor were they associated with the aggressive HGSOC subtype or the stage of disease at the initial diagnosis.