Present Data Research Articles

Prevalence and Correlates of Dry Eye in a German Population Sample.

In this cross-sectional survey, we assessed the prevalence of dry eye disease (DED) in a representative German population sample. In addition, we examined the associations between DED, health-related quality of life (HRQoL), and level of fatigue. Finally, we further validated the German version of the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire and present norm data of the German population. A random sample of German residents aged 16 years and older was recruited between October and December 2021. All participants completed the SPEED, Short Form 36, and Multidimensional Fatigue Inventory 20 questionnaires. Of the 2495 participants who completed the survey, 450 (21.6%; 95% confidence intervals 20.0-23.1) reported a SPEED total score of ≥4, indicating a positive screening for DED. DED was significantly more common in women and older age. Participants who screened positive for DED reported significantly higher levels of fatigue and lower values in all domains of HRQoL. A receiver operating characteristic curve of the SPEED was generated using an ophthalmologist's diagnosis. The area under the curve was estimated to be 0.886 (95% confidence intervals 0.858-0.913). A cutoff score ≥4 seemed to be appropriate as an indicator of DED. Cronbach's α was excellent (0.95). DED is common in the German population. We confirmed associations with sex, age, HRQoL, and fatigue level, indicating a high burden of DED. The German version of the SPEED is a valid instrument for the assessment of DED symptoms.

MIIP downregulates PD-L1 expression through HDAC6 in cutaneous melanoma

PurposeImmune checkpoint inhibitors have improved the objective response rate and survival of melanoma patients. However, there are still many melanoma patients suffering from disease progression due to primary or secondary immune checkpoint inhibitor resistance, as is observed in the failure of anti-PD1/PD-L1 therapy. While the expression of valuable markers, such as TMB, MSI, and PD-L1, could serve as effective predictors of anti-checkpoint inhibitor therapies, tumor cell PD-L1 expression and its regulating mechanism would significantly affect the anti-PD-1 immunotherapy response and efficacy. Therefore, it is urgent to determine the function of PD-1/PD-L1 expression in melanoma and its associated pathways to enhance the efficacy of anti-PD-1 therapies.MethodsA cohort of 133 patients with histologically confirmed melanoma from Tianjin Medical University Cancer Institute & Hospital were included in this study. We performed immunohistochemical staining to detect the expression of Migration and invasion inhibitory protein (MIIP), HDAC6 and PD-L1. Kaplan–Meier and log-rank test were used for survival analysis. As for vitro, Western blot was used in melanoma cell lines to verify the signaling pathway that MIIP regulates PD-L1 expression.ResultsMIIP expression was decreased in melanoma and that the negative expression of MIIP was correlated with worse overall survival. The positive expression of HDAC6, a molecule that is downstream of MIIP, had a positive trend with decreased overall survival. At the same time, the positive expression of PD-L1, a crucial costimulatory molecule, was associated with decreased overall survival. Furthermore, there was a positive association between HDAC6 and PD-L1 protein expression (p < 0.01), and this correlation is more prominent in cutaneous melanoma than acral melanoma. In cutaneous melanoma cell lines, we found that increasing MIIP led to decreased HDAC6, pSTAT3, and PD-L1 expression. Knocking down MIIP led to increased HDAC6, pSTAT3, and PD-L1 expression. Combining the published results, showing that HDAC6 can regulate PD-L1 expression through STAT3, our present data suggest that MIIP inhibits the expression of PD-L1 by downregulating HDAC6 in melanoma. Most importantly, methods for targeting MIIP-HDAC6-PD-L1 pathways, such as treatment with HDAC6 inhibitors, might indicate a new therapeutic approach for enhancing immune checkpoint inhibitor therapies in melanoma.ConclusionsOur findings highlight the immunomodulatory effects of MIIP in the inhibition of PD-L1 expression by downregulating HDAC6 in melanoma. Methods for targeting MIIP-HDAC6-PD-L1 pathways might be new therapeutic approaches for enhancing immune checkpoint inhibitor therapies in melanoma.

Formation of tendinous intersections in the human fetal rectus abdominis.

Previous studies have poorly described the initial development process of the tendinous intersections of the rectus abdominis muscle (RAM). The present study aimed to observe the formation of tendinous intersections in the RAM during the early fetal period using diffusion tensor imaging (DTI). Fifteen human fetal specimens (crown-rump length [CRL]: 39.5-93.7 mm) were selected. Three-dimensional measurements revealed that Zone-4 (i.e., the zone between the pubic symphysis and the caudal base of the umbilical ring in the RAM) had a smaller width and was thicker than Zone-1 and Zone-2 (i.e., the zones between the costal arch and the cranial base of the umbilical ring) and Zone-3 (i.e., the zone at the umbilical ring). Characteristics of tendinous intersections in the RAM during the early fetal period were assessed according to number, size, type, laterality, and sex. The mean number of tendinous intersections on both sides was 3.1 (range: 2.0-4.0), and 21% of specimens had only two tendinous intersections, which was higher than that reported in previous adult studies. The present data suggest that the formation of tendinous intersections was still in progress in specimens with two tendinous intersections in the RAM and that the third tendinous intersection was formed in Zone-2. Ordinal logistic regression via generalized estimating equations revealed that the odds for a higher type of tendinous intersections in Zone-1 and Zone-2 were significantly higher than those in Zone-4 (adjusted odds ratio: 14.85, 8.84). The odds for the presence of incomplete types (tendinous intersections that could not completely transverse the RAM) in Zone-3 were significantly higher than those in Zone-1 (adjusted odds ratio: 7.4). The odds for missing tendinous intersections in Zone-4 were significantly higher than those in Zone-1 (adjusted odds ratio: 20.5). These zonal differences in the formation of tendinous intersections were consistent with those observed in previous adult studies. In this study, DTI detected tendinous intersections in a sample with a CRL of 45.8 mm (approximately 11 weeks of gestation), which is earlier than that in previous histological findings, indicating that the RAM does not have mature tendinous intersections until the 17th week of gestation. In conclusion, DTI could detect the premature differentiation of tendinous intersection formation. Our data may aid in elucidating the developmental processes of tendinous intersections in the RAM.

Winter survival in red clover: experimental evidence for interactions among stresses

BackgroundThere is a lack of knowledge on the combined effects of different stresses on plants, in particular different stresses that occur during winter in temperate climates. Perennial herbaceous plants in temperate regions are exposed to many different stresses during winter, but except for the fact that cold temperatures induce resistance to a number of them, very little is known about their interaction effects. Knowledge about stress interactions is needed in order to predict effects of climate change on both agricultural production and natural ecosystems, and to develop adaptation strategies, e.g., through plant breeding. Here, we conducted a series of experiments under controlled conditions to study the interactions between cold (low positive temperature), clover rot infection (caused by Sclerotinia trifoliorum) and freezing, in red clover (Trifolium pratense) accessions. We also compared our results with winter survival in field experiments and studied associations between stress and shoot growth.ResultsExposure to low positive temperatures (cold acclimation) induced resistance to clover rot. There was a clear negative interaction effect between freezing stress and clover rot infection, resulting in up to 37% lower survival rate compared to what would have been expected from the additive effect of freezing and infection alone. Freezing tolerance could continue to improve during incubation under artificial snow cover at 3 °C in spite of darkness, and we observed compensatory shoot growth following freezing after prolonged incubation. At the accession level, resistance to clover rot was negatively correlated with growth in the field during the previous year at a Norwegian location. It was also negatively correlated with the shoot regrowth of control plants after incubation. Clover rot resistance tests under controlled conditions showed limited correlation with clover rot resistance observed in the field, suggesting that they may reveal variation in more specific resistance mechanisms.ConclusionsWe here demonstrate, for the first time, a strong negative interaction between freezing and infection with a winter pathogen. We also characterize the effects of cold acclimation and incubation in darkness at different temperatures on winter stress tolerance, and present data that support the notion that annual cycles of growth and stress resistance are associated at the genetic level.

Influence of genetics variants of the IL6 gene on major depressive disorder: a review

The aim of this study was to elucidate the clinical picture of Major Depressive Disorder (MDD) with polymorphisms involving the IL6 gene. It was a systematic review with a search for original articles in the Scopus, Web of Science, PubMed, and BVS databases, which provided information on genetic variants related to IL6 gene polymorphisms. Studies that did not present complete data, including statistical data, were excluded. Fifty-four articles were found in the databases. The Rayyan platform was used to remove duplicates and read abstracts for initial selection. Twelve articles remained, and those that were freely accessible were selected for full reading, totaling 5 articles for this review. Evidence suggests a systemic condition in MDD, with data demonstrating inflammatory alterations. Given that in most studies, patients with MDD had higher inflammatory states, there appears to be a relationship between IL-6 and the disorder. IL-6 induces changes in the brain, activates microglia, and controls neuronal health, potentially making the relationship between polymorphisms and the disease tangible, but there are still few studies in the field.

Primary Renal Angiosarcoma: Rare Tumour with Lethal Outcomes

Introduction: Renal haemangioma is a benign tumour, and due to its characteristics, it must be distinguished from malignant diseases. We present a clinical case of primary renal angiosarcoma initially mistaken for haemangioma due to their similarity. Case report: A 58-year-old man was admitted to the hospital with suspicion of pulmonary embolism. The patient complained of pain on the left side. An ultrasound and CT scan of the abdomen showed a tumour mass ~20.5 × 17.2 × 15.4 cm in size in the projection of the left kidney. On CT images, there were data for clear cell renal clear cell carcinoma (ccRCC). A left nephrectomy was performed. However, histological examination revealed renal haemangioma. Three months later, the patient presented to the hospital with abdominal and lumbar pain. A CT scan showed multiple small hypoechoic foci up to 2 cm in size in the liver, lungs, and intra-abdominally, with the most data for carcinosis. Histological re-verification of the left kidney showed a renal vascular tumour with pronounced signs of infarction and necrosis with the majority of the evidence supporting angiosarcoma. Despite treatment, the patient’s outcome was fatal. Conclusions: Based on the clinical presentation, radiological images and histological examination data, the tumour was initially misdiagnosed as kidney haemangioma. Due to the rarity of this tumour, there are no established treatment protocols or clinical guidelines for managing primary kidney angiosarcoma.

Thrift Business Network Analysis at Happy Thrift Stuf

This study aims to comprehend and examine the functioning of the thrift business network at Happythrifstuff. The data collection methods utilized in this study encompass interviews and documentation. The research methodology is a descriptive qualitative approach, which entails collecting, organizing, and presenting data obtained during the study to achieve precise and thorough information. The data suggest that the thrift business network at Happythrifstuff acquires items from Bandung (Gede Bage), which are obtained from distributors in Batam (Sumatra), with the leading suppliers in Korea and Japan. The analysis indicates that the thrift company is well-suited for students or individuals who want to establish an enterprise with relatively small cash and the potential for profitable earnings. This is apparent from the original capital expenditure of 40 goods amounting to Rp. 5,740,000, resulting in Rp profit revenue. 1,148,000 from the sale of 40 products. This essay aims to inspire individuals to engage in the second-hand goods industry, to create cash, and to assist in fulfilling everyday necessities.

The classical supraorbital minicraniotomy to approach the areas of origin of anterior skull base meningiomas: Anatomical nuances influencing accessibility, operability, and frontal lobe retraction

Background: The classical supraorbital minicraniotomy (cSOM) constitutes a minimally invasive alternative for the resection of anterior skull base meningiomas (ASBM). Surgical success depends strongly on optimal patient selection and surgery planning, for which a careful assessment of tumor characteristics, approach trajectory, and bony anterior skull base anatomy is required. Still, morphometrical studies searching for relevant anatomical factors with surgical relevance when intending a cSOM for ASBM resection are lacking. Methods: Bilateral cSOM was done in five formaldehyde-fixed heads toward the areas of origin of ASBM. Morphometrical data with potential relevant surgical implications were analyzed. Results: The more tangential position of the cSOM with respect to the olfactory groove (OG) led to a reduction in surgical freedom (SF) in this area compared to others (P &lt; 0.0001). Frontal lobe retraction (FLR) was also higher when approaching the OG (P &lt; 0.05). Olfactory nerve mobilization was higher when accessing the planum sphenoidale (PS), tuberculum sellae (TS), and anterior clinoid process (ACP) (P &lt; 0.0001). OG depth and the slope of the sphenoid bone between the PS and TS predicted lower SF and higher frontal retraction requirements along the OG and TS, respectively (P &lt; 0.05). In contrast, longer distances to the ACP tip predicted lower SF over this structure (P &lt; 0.01). Conclusion: Although clinical validation is still needed, the present anatomical data suggest that assessing minicraniotomy’s position/extension, OG depth, the sphenoid’s slope, and distance to ACP-tip might be of particular relevance to predict FLR, maneuverability, and accessibility when considering the cSOM for ASBM resection, thus helping surgeons optimize patient selection and surgical strategy.

Real life experience with point by point pulsed field ablation for recurrent ventricular arrhythmias

Abstract Introduction The safety and effectiveness of electroporation/point by point pulsed field ablation (PP PFA) as emerging technoloy for catheter ablation (CA) of ventricular arrhythmias (VAs) has been described till now only in case reports. Purpose The aim of this observational retrospective study is to present real life data concerning the overall performance of PP PFA for CA of recurrent VA. Methods A total number of 13 consecutive patients (11 VTs and 2 PVCs), in whom recurrent VTs after RF ablation documented, were included. In all patients the substrate location was documented beforehand based on cardiac MRI or CT with myocardial thinning. For substrate mapping a high resolution multipoint mapping catheter was used. A complete success was defined as non inducibility of any arrhythmia at the end of procedure respectively lack of VA recurrence at follow – up. Results Excepting 2 patients, all other had a non ischemic cardiomyopathy as underlying heart disease (mean age 63 ± 8 y/o, mean LVEF 42 % ± 9 %). In every patient at least one conventional RF CA has been performed previously (mean 2 ± 1) and 38 % of patients had a previous epicardial RF VT ablation. The PP PFA VT ablation was performed endocardialy in 11 patients (84 %), respectively epicardialy in 2 patients. The ablation sites had a septal location in 53 % of patients and other localisation in 47 % of patients. The applied energy was 25 A. The overall acute complete success was achieved in 77 % patients. At medium 6 ± 3 months follow up a complete success was present in 46 % cases. Most frequently a VT recurrence after PP PFA ablation was encountered in patients with combined septal and nonseptal substrate distrubution. After PP PFA, the RF CA strategy due to recurrent VAs was endocardial in 2 patients, respectively epicardial 2 in cases and bipolar in 1 case. No PP PFA redos were undergone. Three major complications have been documented (1 tamponade, 1 AV block III° and 1 complete LBBB). Conclusion As bailout strategy in patients with failed conventional CA, PP PFA represents a safe strategy. Specific complications like temporary atrioventricular or intraventricular conduction disturbancies are extremely rare, reversible but not life threathening. The midterm success is satisfactory but still limited in patients with intramural substrate.

LVNC or hyper-trabeculated LV, are we missing something?

Abstract Introduction LVNC is a heterogeneous poorly understood entity characterized by prominent myocardial trabeculation.(1) It often overlaps with other phenotypes such as DCM, HCM.(2) Incidence of SCD is highly variable, however it may account for about 50% of all mortality in LVNC.(3) Risk stratification of SCD is a complex matter. Despite that current guidelines recommend following the same principles of 1ry prevention as in DCM based on similar CV mortality risk, it seems of utmost importance to identify additional features which could be specifically associated with LVNC and contributing to a higher risk of adverse events particularly ventricular arrhythmia (VA). Purpose To identify possible high risk features for prediction of ventricular arrhythmia in the form of documented NSVT, VT, or VF in LVNC. Methods This is a retrospective single centre cohort study of patients fulfilling the LVNC defining criteria from 2018 to 2023. Patients’ data were reviewed for family history of cardiomyopathies or SCD, clinical presentation, ECGs data in the form of QRS duration, QTc interval and Tp-e, Holter analysis, CIEDs interrogation if present and MRI data including LVEF, volumes, fibrosis burden and distribution, NC/C ratio, NC / LV global mass ratio, global longitudinal strain"GLS", global circumferential strain "GCS" , global radial strain "GRS" , extent of hypertrabeculation, RV involvement in the form of EF, volumes, hypertrabeculation. Results A total of 42 patients were included (34+/- 17 years of age, 57% males). 5 patients of our cohort were pediatrics. Mean LVEF 45%. LGE was detected in 14% of cases, RV involvement in 38 %. Ventricular arrhythmia were present in 15 patients (35%), of which 6 patients had malignant ventricular arrhythmia. LVEF, NC/LV global mass ratio, LVGLS, LVGCS were found to be significantly correlated with the occurrence of VA with cut-off values of &amp;lt;43%, &amp;gt;31%, &amp;lt;-15 and &amp;lt;-13.5 respectively. While positive FH, RV involvement, pattern, burden of LV fibrosis and ECG parameters didn’t significantly increase the incidence of VA. In a multivariate regression analysis NC to LV global mass ratio was the sole independent predictor of VA ( p value=0.024). ICDs were implanted in 10 cases, 8 were for 1ry prevention based on clinical judgement, 4 of them received appropriate ICD therapy. Conclusion LVNC is associated with increased risk of VA. In addition to clinical assessment and LVEF, CMR can add a different insight for risk stratification. Interestingly, LGE wasn’t associated with significantly increased risk of VA "taking into consideration LGE was found only in 14% of cases" highlighting the potential role the trabeculated myocardium in the pathophysiology of VA by altering the electrical stability of the heart. Finally, these findings could contribute in answering an ongoing question; Should LVNC with its unique characteristics be treated as a special entity with its own high-risk criteria for VA and SCD?LV NC/global mass ration and GLSDemographic,clinical,ECG and MRI data

High-order discretization–based self-adaptive turbulence eddy simulation for supersonic base flow with PHengLEI software

PurposeThe purpose of the present study is to develop a new numerical framework that can predict the supersonic base flow more accurately, including the development of axisymmetrically separated shear layer and recompression shock. To this end, two aspects are improved and combined, i.e. a newly self-adaptive turbulence eddy simulation (SATES) turbulence modeling method and a high-order discretization numerical scheme. Furthermore, the performance of the new numerical framework within a general-purpose PHengLEI software is assessed in detail.Design/methodology/approachSatisfactory prediction of the supersonic separated shear layer with unsteady wake flow is quite challenging. By using a unified turbulence model called SATES combining high-order accurate discretization numerical schemes, the present study first assesses the performance of newly developed SATES for supersonic axisymmetric separation flows. A high-order finite differencing-based compressible computational fluid dynamics (CFD) code called PHengLEI is developed and several different numerical schemes are used to investigate the effects on shock-turbulence interactions, which include the monotonic upstream-centered scheme for conservation laws (MUSCL), weighted compact nonlinear scheme (WCNS) and hybrid cell-edge and cell-node dissipative compact scheme (HDCS).FindingsCompared with the available experimental data and the numerical predictions, the results of SATES by using high-order accurate WCNS or HDCS schemes agree better with the experiments than the results by using the MUSCL scheme. The WCNS and HDCS can also significantly improve the prediction of flow physics in terms of the instability of the annular shear layer and the evolution of the turbulent wake.Research limitations/implicationsThe small deviations in the recirculation region can be found between the present numerical results and experimental data, which could be caused by the inaccurate incoming boundary layer condition and compressible effects. Therefore, a proper incoming boundary layer condition with turbulent fluctuations and compressibility effects need to be considered to further improve the accuracy of simulations.Practical implicationsThe present study evaluates a high-order discretization-based SATES turbulence model for supersonic separation flows, which is quite valuable for improving the calculation accuracy of aeronautics applications, especially in supersonic conditions.Originality/valueFor the first time, the newly developed SATES turbulence modeling method combining the high-order accurate WCNS or HDCS numerical schemes is implemented on the PHengLEI software and successfully applied for the simulations of supersonic separation flows, and satisfactory results are obtained. The unsteady evolutions of the supersonic annular shear layer are analyzed, and the hairpin vortex structures are found in the simulation.

Anthropogenic gadolinium in the Tone River (Japan): an update showing a 7.7-fold increase from 1996 to 2020

BackgroundAnthropogenic gadolinium (Gd), originating from Gd-based contrast agents (GBCAs) used in magnetic resonance imaging (MRI), is widely identified in the aquatic environment with concerns about toxicity and accumulation. We aimed to present new data on anthropogenic Gd in the Tone River, which has the largest drainage area in Japan, and then to compare the current data with those obtained in 1996.MethodsThe water samples were collected on August 9−10, 2020, at 15 different locations of the Tone River in Japan. The concentrations of the rare earth elements (REEs) were measured by inductively coupled plasma-mass spectrometry and normalized to Post-Archean Australian Shale to construct shale-normalized REE patterns. The degree of Gd-anomaly was defined as the percentage of anthropogenic Gd to the geogenic background and used to compare the water samples from different locations. Pearson’s correlation coefficients were calculated.ResultsAll the samples displayed positive Gd anomalies. The Gd-anomaly ranged from 121 to 6,545% and displayed a repeating decrease-and-increase trend. The Gd-anomaly showed strong positive correlations to the number of hospitals (r = 0.88; p < 0.001) and their MRI units (r = 0.89; p < 0.001).ConclusionsOur study revealed notable anomalies of Gd concentrations in river water in Japan, with strong positive correlations to the number of major hospitals and their MRI units. Compared with the previous report in 2000, the Gd-anomaly in Tone River increased from 851% (sampled in 1996) to 6,545%, i.e., 7.7 times, reflecting the increased use of GBCAs in hospitals.Relevance statementNotable Gd concentration anomalies in river water in Japan were observed. This result underlines the importance of more extensive research on anthropogenic gadolinium, and investigations of risks to human health as well as the development of effective removal technologies may be necessary.Key points• All water samples from Tone River displayed positive Gd anomalies.• The Gd anomalies increased to 7.7 times higher over the past 24 years.• Correlations between Gd values and the number of hospitals and MRI units were observed.Graphical

PALEOPARASITOLOGICAL CONTRIBUTIONS TO THE STUDY ON ANCIENT INFECTIONS OF HOMINIDS AND OTHER VERTEBRATES IN BRAZIL: A REVIEW

Paleoparasitology is an interdisciplinary science that studies the parasitic infections in the past, using fossils and subfossils recovered from archeological and paleontological lithostratigraphic units. During the 20th and 21st centuries, it has improved the biological knowledge on helminths and protozoans, as well as provided numerous sociocultural insights into the past civilizations. Here, we present an updated review of the paleoparasitological contributions to the analyses of ancient infections in vertebrate remains recovered from different regions of Brazil. Since its emergence, the Paleoparasitology has been important to a multidisciplinary knowledge related to sociocultural aspects of the American Pre-Columbian civilizations and may provide an important ecological, evolutionary, and biogeographical understanding of parasites of vertebrates other than humans throughout the geological time. The present data compilation suggests a prominent role in the scientific community assumed by paleoparasitological approaches, since they have been contributing to a better understanding of helminth and protozoan distribution in South America, during the Phanerozoic eon and consolidating the Paleoparasitology as a global science. Keywords: Coprolite, mummy, helminth, protozoa.

#2320 The impact of interventions for people with chronic kidney disease on health-related quality of life: a systematic review

Abstract Background and Aims Health-related quality of life (HRQoL) is poorer for those with chronic kidney disease (CKD) than the general population and worsens as CKD progresses. Evidence is mixed as to which interventions improve HRQoL for those with CKD, and HRQoL is often under-reported in randomised controlled trials where it is most commonly a secondary outcome. Reviews including HRQoL as an outcome have thus far focused on the impact per intervention, therefore we aimed to ascertain which interventions, of any type, have an impact on HRQoL outcomes for those with non-dialysis dependent CKD (NDD-CKD). Method The protocol was prospectively registered on PROSPERO (CRD42022364474) and PRISMA guidelines were followed. Inclusion criteria were randomised controlled trials in an NDD-CKD population (excluding transplant recipients), any intervention type, usual care/placebo comparators, using validated and reported HRQoL outcomes measures. Databases searched were Embase, Medline, PsychINFO, CINAHL plus, Web of Science, PubMed, and Google Scholar, with reference searching of included studies. Reports were independently screened by two researchers who also performed data extraction and quality assessment (using the Cochrane Risk of Bias 2.0 tool). Synthesis was undertaken using Synthesis without Meta-analysis (SWiM) methods. Conversion to one-sided p-values, synthesising outcomes in albatross plots and combining p-values via Fisher's method was performed using the metap package in R. HRQoL measures were broken down into physical, mental, kidney disease symptoms, adverse effects of kidney disease, burden of kidney disease, overall kidney disease, and overall HRQoL domains for analysis. Results Searches yielded 8983 records, and 39 studies met inclusion criteria, with a total of 11,940 participants. Nine groups were formed based on type of intervention, with data synthesis possible in the eight groups with more than one study (Fig. 1). 26 (66%) studies were rated as having high risk of bias, largely due to frequent lack of blinding and HRQoL being a patient reported outcome. 37 studies had sufficient data for presentation in albatross plots (Fig. 2). Using combined p-values for all HRQoL outcomes in each group of studies, benefit to HRQoL in at least one study was shown for education interventions (p &amp;lt; 0.001, seven studies, none with low risk of bias), exercise interventions (p &amp;lt; 0.001, eight studies, all with high risk of bias), medications to treat CKD-related anaemia (p &amp;lt; 0.001, eight studies, four with low risk of bias), nutritional interventions (p &amp;lt; 0.001, four studies, all with high risk of bias) and weight loss interventions (p &amp;lt; 0.001, two studies, one with low risk of bias). No benefit to HRQoL was shown for medications aimed at slowing CKD progression (p = 0.492, five studies), medications for depression (p = 0.266, two studies) and medications to treat acidosis (p = 0.99, two studies). Conclusion This review identified several interventions with evidence of benefit to HRQoL for people with NDD-CKD, including medications to treat anaemia and weight loss interventions. Studies of education, exercise and nutritional interventions showed potential benefit, but with high risk of bias. Further high-quality randomised controlled trials of interventions for people with NDD-CKD should include and report HRQoL outcomes, in addition to targeting potentially modifiable determinants of HRQoL in these groups.

#1290 Adverse proinflammatory responses in the kidney after FGF23 administration in three murine kidney disease models

Abstract Background and Aims The hormone FGF23 is a biomarker associated with morbidity and mortality in individuals with and without kidney disease, but the role of FGF23 excess as a pathogenic factor is incompletely understood. Here, we investigated renal FGF23 signaling in kidney disease models. Method This study used three independent disease models: i) Male C57BL/6 mice (n = 16) were treated with Freud's adjuvant and nephrotoxic serum (NTS) to induce anti-glomerular basement membrane (anti-GBM) disease. ii) Female BALB/c mice (n = 8) were treated with adriamycin (doxorubicin) 10.5 mg/kg to induce focal and segmental glomerulosclerosis (FSGS). iii) Male DBA/2J mice (n = 20) were fed a diet containing adenine 0.2%. Control mice of the respective same strain and sex received vehicle injections. Mice of the anti-GBM and FSGS models and controls received intravenous injections of recombinant FGF23 1 µg or vehicle for six consecutive days (anti-GBM) or once (FSGS), with dissection 24 h after the last injection. Mice of the adenine model were dissected after 15 weeks. Following dissection, ex vivo precision-cut kidney slices (PCKS) were obtained from n = 4 mice and maintained for 24 at 37°C, 95% O2 and 5% CO2, followed by a 1 h treatment with recombinant FGF23 200 ng/ml or vehicle. Glomerular filtration rate (GFR) or renal retention parameters in serum and albuminuria were assessed. Kidneys underwent histological assessment using hematoxylin &amp; eosin or Masson's trichrome. Renal RNA was isolated for bulk RNAseq. Differential gene expression was assessed to determine the effect of FGF23 treatment in disease-free controls, in each disease model, and the interaction between FGF23 X disease effect for the anti-GBM and FSGS groups. Gene set enrichment analysis was performed with a focus on the immune system. Results Anti-GBM mice showed a 45 ± 27% GFR decline (mean ± SD) compared to baseline, whereas controls showed an GFR increase of 11 ± 36% (p &amp;lt; 0.01). Kidney histology revealed an interstitial infiltrate. The FSGS model showed elevated serum creatinine and albuminuria, and hypercellularity in some glomeruli. Mice of the adenine model showed progressively increased blood urea nitrogen concentrations starting after 2 weeks, up to a 3-fold increase at week 14. Histology revealed interstitial fibrosis and tubular atrophy. Bulk RNAseq revealed proinflammatory transcriptional signatures after FGF23 treatment in all disease models, regardless of which timepoint or model: In the anti-GBM model, Hallmark gene sets of inflammatory response, interferon-α response, interferon-β response and allograft rejection were significantly increased after 6 days of FGF23 treatment, whereas disease-free controls showed no significantly changed immune gene sets after 6 days of FGF23. In FSGS mice, none of the Hallmark gene sets were changed after 1 FGF23 injection, but top individual gene expression affected by 1 FGF23 injection were an increased proinflammatory transcription factor Cebpb and an increased DNA damage transcript Dclre1b. Finally, the PCKS of adenine model revealed no significant Hallmark gene sets, but the two genes with differential expression were a proinflammatory macrophage/fibroblast chemokine Ccl4 (increased) and an immunoglobulin heavy variable Ighv2-2 (decreased). Conclusion FGF23-driven patterns of proinflammatory gene expression were observed in three experimental models of kidney disease, both in vivo and ex vivo assessment of FGF23 signaling, thus excluding effects of FGF23 on other organs. As these findings were limited to transcriptional analyses, the present data warrant further confirmation and exploration of FGF23 as a pathogenic agent in kidney disease.

Novel Li‐Ion Battery Diagnostics; Detection of Redox Peaks Utilising Plasmonic Fibre Optic Sensors and Evaluation of Interference on Cell Function

AbstractIn this study we demonstrate detection of redox peaks in Li‐ion pouch cells during cyclic voltammetry (CV), via the optical signal of plasmonic based fibre optic sensors placed inside Li‐ion pouch cells. The sensors are placed inside the pouch cells during manufacture, allowing diagnostic data to be obtained from directly inside the cells in real time. We further present data showing the battery cell remains agnostic to the presence of fibre optic sensors over repeated cycling through analysis of the formation cycles, electrochemical impedance spectroscopy (EIS) analysis, coulombic efficiency data, capacity data and post‐mortem materials analysis. This study provides evidence of the utility of fibre optic based diagnostic sensors, and in particular the novel use of plasmonic based fibre optic sensors, as an in situ battery diagnostic technique and potential research tool to investigate battery cell phenomena.

Response to editorial: Gastric and pancreatic cancer trends in Spain.

This response to an editorial discusses recent trends in gastric and pancreatic cancer mortality in Spain. The authors acknowledge the contrasting trajectories - a decrease in gastric cancer and an increase in pancreatic cancer - and attribute them to differing causes. Public health measures, particularly H. pylori eradication, are credited for the decline in gastric cancer. The authors also present unpublished data showing a worrying rise in gastric cancer diagnoses among young men. They emphasize the need for continued monitoring, early detection strategies, and preventative measures to tackle both cancers, particularly focusing on pancreatic cancer research due to its rising mortality.

Nondestructive quantification of internal raster path for additively manufactured components via ultrasonic testing.

This work investigates the viability of discerning the raster pattern of additively manufactured components using high frequency ultrasonic nondestructive testing. Test coupons were fabricated from poly cyclohexylenedimethylene terephthalate glycol using the fused filament fabrication process, in which layers were deposited at various predetermined raster angles. Each printed part was scanned using spherically focused, high-resolution, ultrasonic transducers of various peak frequencies between 7.5 and 15MHz. From the captured waveform data, images are extracted to observe the raster pattern in a layer-by-layer manner, with the results from the 10MHz element yielding the best performance. An in-house MATLAB script was developed to analyze the transducer signal to investigate C-scan images at various depths throughout the component. From the resulting C-scan images, one can consistently identify the proper raster orientation within 2°-4° in each of the first 10 deposited layers, with the accuracy decreasing as a function of depth into the component. Due to signal attenuation, there is insufficient data at depths beyond the 11th and 12th layer, to properly analyze the present data sets accurately. Validation was performed using X-ray computed tomography scans to demonstrate the accuracy of the ultrasonic inspection method.

Symptomatic progression of frontotemporal dementia with the TARDBP I383V variant

ABSTRACT We present a longitudinal description of a man with the TARDBP I383V variant of frontotemporal dementia (FTD). His progressive changes in behavior and language resulted in a diagnosis of the right temporal variant of FTD, also called the semantic behavioral variant (sbvFTD). We also present data from a small series of patients with the TARDBP I383V variant who were enrolled in a nationwide FTD research collaboration (ALLFTD). These data support slowly progressive loss of semantic function. While semantic dementia is infrequently considered genetic, the TARDBP I383V variant seems to be an exception. Longitudinal analyses in larger samples are warranted.

How Much Retrieval Ability Is in Originality?

ABSTRACTCreative fluency and originality are pivotal indicators of creative potential. Both have been embedded in hierarchical intelligence models as part of the ability to retrieve information from long‐term memory; an ability that is often measured with indicators of retrieval fluency. Creative fluency and retrieval fluency, both expressed by the count of correct responses, are procedurally highly similar. This raises the question how creative fluency and originality are related with retrieval fluency and how both are predicted by other cognitive abilities. In a multivariate study (N = 320), we found that retrieval fluency is very strongly related with creative fluency (r = .87) and substantially related with originality (r = .59). A combined fluency factor still fitted the data well. Cognitive abilities accounted for 63% variance in fluency and 47% variance in originality. After controlling for established cognitive abilities, latent variables for fluency and originality were unrelated with one another. This suggests that the procedural proximity of the ability to fluently generate either information from long‐term memory or ad‐hoc solutions to unusual tasks and the ability to come up with original ideas needs reconsideration. Locating originality below an overarching retrieval factor is contradicted by the present data.