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A new species of Symphyla, Hanseniella guerreroi sp. nov., is described from specimens collected during expeditions to the Tierra del Fuego archipelago, including Isla Grande de Tierra del Fuego and Isla de los Estados in Argentina, as well as Isla Navarino in Chile. To the best of our knowledge, this new species represents the southernmost record for a myriapod of the class Symphyla. The morphological affinities of this species with other Hanseniella species from Gondwanan landmasses are discussed, highlighting its potential for studying the impact of the last Quaternary glaciation on soil arthropods in the far south of the continent. This discovery provides important insights into the biogeographic and evolutionary history of soil arthropods in these remote and climatically challenging regions. H. guerreroi sp. nov. is an exemplary species adapted to the harsh environmental conditions of subantarctic ecosystems and contributes significantly to our understanding of biodiversity and ecological dynamics in such challenging habitats.

Abstract Structural variants (SVs) are significant contributors to inter-individual genetic variation associated with traits and diseases. Current SV studies using whole-genome sequencing (WGS) have a largely Eurocentric composition, with little known about SV diversity in other ancestries, particularly from Asia. Here, we present a WGS catalogue of 73,035 SVs from 8392 Singaporeans of East Asian, Southeast Asian and South Asian ancestries, of which ~65% (47,770 SVs) are novel. We show that Asian populations can be stratified by their global SV patterns and identified 42,239 novel SVs that are specific to Asian populations. 52% of these novel SVs are restricted to one of the three major ancestry groups studied (Indian, Chinese or Malay). We uncovered SVs affecting major clinically actionable loci. Lastly, by identifying SVs in linkage disequilibrium with single-nucleotide variants, we demonstrate the utility of our SV catalogue in the fine-mapping of Asian GWAS variants and identification of potential causative variants. These results augment our knowledge of structural variation across human populations, thereby reducing current ancestry biases in global references of genetic variation afflicting equity, diversity and inclusion in genetic research.

Background: Aortic valve stenosis (AVS) is a common valvular heart disease affecting millions of people worldwide. It leads to significant neurocognitive and neuropsychological impairments, impacting patients’ quality of life. Objective: The objective of this article is to identify and discuss the potential neurocognitive effects on patients with aortic stenosis before and after undergoing surgical aortic valve replacement (SAVR). Method: Our study involved the assessment of 64 patients undergoing aortic valve replacement (SAVR) using a neurocognitive evaluation comprising a battery of 11 different cognitive tests. These tests were designed to analyze the patients’ overall cognitive functioning, executive abilities, short- and long-term memory, and attentional performance. The tests were administered to patients before the aortic valve surgery (T0) and after the surgery (T1). From a statistical perspective, numerical variables are presented as means (±standard deviation) and medians (IQR), while categorical variables are presented as counts and percentages. Normality was assessed using the Shapiro–Wilk test. T0 and T1 scores were compared with the Wilcoxon signed rank test, with p < 0.05 considered significant. Analyses were performed using SAS version 9.4. Results: Conducted as part of a fully financed Italian Ministry of Health project (RF-2016-02361069), the study found that most patients showed normal cognitive functioning at baseline. Cognitive assessments showed that executive functions, attention, language, and semantic knowledge were within the normal range for the majority of participants. After SAVR, cognitive outcomes remained stable or improved, particularly in executive functions and language. Notably, verbal episodic memory demonstrated significant improvement, with the percentage of patients scoring within the normal range on the BSRT increasing from 73.4% at T0 to 92.2% at T1 (p < 0.0001). However, visuospatial and visuoconstructive abilities showed stability or slight decline, while attentional skills remained relatively stable. The Clock Drawing Test indicated the maintenance of cognitive functions. Conclusions: The findings of our study indicate a global stability in cognitive status among patients after undergoing SAVR, with significant improvement noted in verbal episodic memory. While other cognitive domains did not demonstrate statistically significant changes, these insights are valuable for understanding the cognitive effects of SAVR and can guide future research and clinical practice in selecting the most effective surgical and rehabilitative options for patients. Monitoring cognitive outcomes in patients undergoing aortic valve replacement surgery remains crucial.

Abstract Background Long-chain fatty acid oxidation disorders (LC-FAOD) are rare and potentially life-threatening diseases that cause deficient energy production and accumulation of toxic metabolites. Despite dietary management, adherence to maximum fasting guidelines, restricted long-chain triglyceride intake and supplementation with medium-chain triglyceride (MCT) oil (current standard of care), most patients experience recurrent decompensation episodes that can require hospitalisation. Herein, we analysed the effectiveness and safety of triheptanoin (a highly purified, synthetic medium odd-chain triglyceride) treatment in a cohort of Italian patients with LC-FAOD. Methods This retrospective, nationwide study included nine patients with LC-FAOD who switched from standard therapy with MCT oil to triheptanoin oral liquid. Data were collected between 2018 and 2022. Clinical outcome measures were the number and duration of intercurrent catabolic episodes and number and duration of metabolic decompensation episodes requiring hospitalisation. Creatine kinase (CK) levels and treatment-related adverse effects were also reported. Results Patients were provided a mean ± standard deviation (SD) triheptanoin dose of 1.5 ± 0.9 g/kg/day in four divided administrations, which accounted for 23.9 ± 8.9% of patients’ total daily caloric intake. Triheptanoin treatment was started between 2.7 and 16 years of age and was continued for 2.2 ± 0.9 years. The number of intercurrent catabolic episodes during triheptanoin treatment was significantly lower than during MCT therapy (4.3 ± 5.3 vs 22.0 ± 22.2; p = 0.034), as were the number of metabolic decompensations requiring hospitalisation (mean ± SD: 2.0 ± 2.5 vs 18.3 ± 17.7; p = 0.014), and annualised hospitalisation rates and duration. Mean CK levels (outside metabolic decompensation episodes) were lower with triheptanoin treatment versus MCT oil for seven patients. No intensive care unit admissions were required during triheptanoin treatment. Epigastric pain and diarrhoea were recorded as adverse effects during both MCT and triheptanoin treatment. Conclusions The significant improvement in clinical outcome measures after the administration of triheptanoin highlights that this treatment approach can be more effective than MCT supplementation in patients with LC-FAOD. Triheptanoin was well tolerated and decreased the number of intercurrent catabolic episodes, metabolic decompensation episodes requiring hospitalisation, and the annualised rate and duration of hospitalisations.

Abstract Electrical storm (ES) is a life-threatening condition of recurrent ventricular arrhythmias (VA) in a short period of time. Percutaneous stellate ganglion blockade (SGB) is frequently used – however the efficacy is undefined. The objective of our systematic review was to determine the efficacy of SGB in reducing VA events and mortality among patients with ES. A search of Medline, EMBASE, Scopus, CINAHL and CENTRAL was performed on February 29, 2024 to include studies with adult patients (≥ 18 years) with ES treated with SGB. Our outcomes of interest were VA burden pre- and post-SGB, and in-hospital/30-day mortality. A total of 553 ES episodes in 542 patients from 15 observational studies were included. Treated VAs pre- and post-SGB were pooled from eight studies including 383 patients and demonstrated a decrease from 3.5 (IQR 2.25–7.25) to 0 (IQR 0–0) events (p = 0.008). Complete resolution after SGB occurred in 190 of 294 patients (64.6%). Despite this, in-hospital or 30-day mortality remained high occurring in 140 of 527 patients (random effects prevalence 22%). Repeat SGB for recurrent VAs was performed in 132 of 490 patients (random effects prevalence 21%). In conclusion, observational data suggests SGB may be effective in reducing VAs in ES. Definitive studies for SGB in VA management are needed. Study protocol: PROSPERO - registration number CRD42023430031.

This study investigated parents' and siblings' knowledge use during naturalistic teaching episodes in the home. Thirty-seven middle-class families were observed for six 90-minute sessions (siblings aged 4 and 6 years). Parent and sibling teaching sequences were coded for knowledge type (conceptual, procedural), conceptual subcategories (social conventional behavior; game discussions; academic concepts; problem solving) and procedural knowledge subcategories (game procedures; general skill procedures). Research Findings: Findings indicated no significant mean difference between mothers' and fathers' and older and younger siblings' conceptual and procedural teaching. However, parents taught proportionally more conceptual knowledge than siblings, indicating that siblings taught proportionally more procedural knowledge compared to parents. In terms of conceptual subcategories, parents taught more social conventional behaviors, whereas siblings taught more academic concepts. Siblings also taught more general skill procedures compared to parents. Practice or Policy: Overall, our findings indicate that the home environment is a rich context for the naturalistic teaching of conceptual and procedural knowledge by both parents and siblings, thus advancing our understanding of the role of family dynamics on children's learning and development.

Differentiated instruction (DI) is a pedagogical framework to which all students can be engaged in their learning and achieve academically in their schooling. While DI is for all students, there is little research in DI for students with learning difficulties, in senior-secondary schools in Australia. This research formed part of a larger study, which recruited 12 participants across two Australian states, to investigate how teachers in senior-secondary schooling, differentiate for students with learning difficulties. Findings indicated that when students had labelled learning difficulties as recognised by other professionals, teachers expressed being able to differentiate more easily with greater self-efficacy, as compared with differentiating for students who teachers themselves considered were experiencing difficulties in their learning but had no label assigned to them. Teachers voiced that learning difficulties was a broad concept, with each teacher defining learning difficulties differently. This suggests that with the broad nature of learning difficulties, teachers may struggle to differentiate accordingly, leading to lower self-efficacy beliefs. While labelled learning difficulties provide guidance for differentiating, this may also see teachers differentiating based on preconceived ideas and for students with special needs, rather than individual students' current understanding. Implications for future practice are discussed.

Purpose: Writing a thesis is a difficult endeavor for undergraduate students, especially in management careers, due to the highly practical approach of the discipline. Students often find difficult to understand and apply research methods in concrete research projects, so a proper set of teaching-learning strategies is critical. This study aimed to examine the effect of these strategies on the academic performance of students in two research seminars in an undergraduate management program in Peru. Design/methodology/approach: The research adopted a mixed approach. The quantitative component included a survey of 249 students in both seminars, while the qualitative one involved only some of the students using three focus groups. The corresponding data analysis included stepwise linear regression models and content analysis. Findings: The study found that a clear course structure, adequate research methods literature, good advisor-student communication and goal planning and achievement were the key determinants of the students' final grades. Originality/value: This research fills a gap in previous studies on the subject by including a broader set of strategies and by statistically estimating the strategies' effects on academic performance.

Objective: The aim of the present study is to examine the relationship between EEG measures and functional recovery in right-hemisphere stroke patients. Methods: Participants with stroke (PS) and neurologically unimpaired controls (UC) were enrolled. At enrolment, all participants were assessed for motor and cognitive functioning with specific scales (motricity index, trunk control test, Level of Cognitive Functioning, and Functional Independence Measure (FIM). Moreover, EEG data were recorded. At discharge, participants were re-tested with the FIM Results: Powers in the delta, theta, alpha, and beta bands and connectivity within the fronto-parietal network were compared between groups. Then, the between-group discriminative EEG measures and the motor/cognitive scales were used to feed a machine learning algorithm to predict FIM scores at discharge and the length of hospitalization (LoH). Higher delta, theta, and beta and impaired connectivity were found in PS compared to UC. Moreover, motor/cognitive functioning, beta power, and fronto-parietal connectivity predicted the FIM score at discharge and the LoH (accuracy=73.2 % and 85.2 % respectively). Conclusions: Results show that the integration of motor/cognitive scales and EEG measures can reveal the rehabilitative potentials of PS predicting their functional outcome and LoH. Significance: Synergistic clinical and electrophysiological models can support rehabilitative decision-making.

Abstract The sedimentary successions of several basins in Europe show evidence of widespread Late Jurassic aridification that is considered a long‐standing conundrum in paleoclimate modeling. The distinctive feature of this event is that it appears concentrated in a discrete time interval between the Kimmeridgian (Late Jurassic) and the Berriasian (Early Cretaceous), and that it extended to eastern and southern‐central Asia for a total of ∼10 Mkm2 in roughly the same time interval. Climate modeling has not provided a convincing explanation for this event. We compiled and reviewed paleomagnetic data from several continents including Adria, the African promontory, showing that this large‐scale aridification was produced by an abrupt and transient southward migration of Eurasia toward arid tropical latitudes, while its demise coincided with a “retromotion” to more humid northern latitudes in the Early Cretaceous. This movement is part of a global plate motion event, most likely due to True Polar Wander, that profoundly affected the depositional environments, the ecosystems, and the architecture of sedimentary basins worldwide.

ABSTRACT Background Recently, a plethora of novel systemic agents have been incorporated into the therapeutic armamentarium of advanced urothelial carcinoma (aUC). The antibody–drug conjugate (ADC), enfortumab vedotin (EV), has demonstrated relevant clinical benefit in patients with aUC refractory to platinum and immune‐checkpoint inhibitor (ICI) therapy. Our study provides a retrospective, international, real‐world analysis comparing the effectiveness of EV to chemotherapy in this setting. Methods The data were extracted from the medical records of patients treated with EV or chemotherapy following pembrolizumab for recurrent or progressive aUC after platinum‐based chemotherapy. Patients were assessed for overall survival (OS), progression‐free survival (PFS), overall response rate (ORR) and duration of response (DoR). Results Our analysis included 247 patients treated with EV (88, 36%) or chemotherapy (159, 64%). Median OS was 9.1 months (95%CI 7.2–10.7) in the overall study population, 13.6 months (95%CI 10.0–31.0) in patients receiving EV and 6.8 months (95%CI 6.0–8.9) in patients receiving chemotherapy (p < 0.001). The OS benefit of EV was not affected by primary tumour site and histology, metastatic sites, type of first platinum‐based chemotherapy or response to pembrolizumab. In the EV cohort, the median PFS was significantly longer (8.8 months [95%CI 6.5–17.0] vs. 3.0 months [95%CI 2.6–3.7]) and the ORR was significantly higher (56% vs. 23%) than in the chemotherapy cohort. Conclusions The results of our international analysis of real‐world data confirm the effectiveness of EV in the sequential strategy of aUC patients who have received prior platinum‐based chemotherapy and anti‐PD‐1 pembrolizumab, regardless of commonly considered prognostic factors. Trial Registration: ClinicalTrials.gov identifier: NCT05290038

Abstract We explored the impact of luspatercept therapy on overall survival (OS) and possible predictors of response in low‐risk (LR) myelodysplastic syndrome (MDS) patients. We evaluated 331 anemic patients treated with luspatercept. Hematological response (HI) was defined as (i) hemoglobin (Hb) increase of ≥1.5 g/dL in nontransfusion‐dependent (NTD) patients, and (ii) red blood cell (RBC) transfusion independence (TI) with a concomitant Hb increase of ≥1.5 g/dL, or RBC‐TI without an Hb increase of 1.5 g/dL, or >50% reduction in RBC transfusion burden (TB) for TD patients. Response was observed in 166 patients (50.2%), with significantly higher response in NTD and low TB versus high TB patients (p

IntroductionSoccer systems promote early identification and specialisation practices to satisfy short- and long-term goals—both from sporting performance and financial gains perspectives. In this context, players are (de)selected based on observed performance level and on their ability to conform to given organisational demands, leading to the proliferation of selection biases, such as relative age effects (RAEs), which research has shown to influence both developmental experiences and senior career achievements. Accordingly, this study aims to: (a) investigate the magnitude of RAEs among youth national teams competing in the UEFA U17 European Soccer Championship, and their associations with teams' final ranking, (b) examine whether RAEs magnitude could be linked to cultural and contextual factors, and (c) further explore RAEs at senior level.MethodsBirth quarter (BQ) distribution of youth national teams (n = 80) that competed in one of the five editions (2018, 2019, 2022, 2023, and 2024) of the UEFA U17 European Soccer Championship was recorded. Teams were classified based on their country of origin, RAEs magnitudes, final ranking in the tournament, FIFA points, and national population. Furthermore, the BQ distribution of senior national teams (n = 24) that competed at the 2024 UEFA Senior European Soccer Championship was recorded.ResultsChi-square statistics revealed BQ1s were overrepresented at the U17 level (p < 0.001) and showed teams exhibiting low RAEs magnitudes recorded the highest likelihood (odds ratio: 5.67) of finishing the tournament in the bottom four positions. Correlation analyses recorded small to moderate positive correlations between RAEs magnitude and national population (.25) and FIFA points (.33). Further chi-square statistics revealed BQ1s continued to be overrepresented at the senior level, albeit with a weaker effect (p

Summary: Tumors are complex ecosystems of interacting cell types. The concept of cancer hallmarks distills this complexity into underlying principles that govern tumor growth. Here, we explore the spatial distribution of cancer hallmarks across 63 primary untreated tumors from 10 cancer types using spatial transcriptomics. We show that hallmark activity is spatially organized, with the cancer compartment contributing to the activity of seven out of 13 hallmarks, while the tumor microenvironment (TME) contributes to the activity of the rest. Additionally, we discover that genomic distance between tumor subclones correlates with differences in hallmark activity, even leading to clone-hallmark specialization. Finally, we demonstrate interdependent relationships between hallmarks at the junctions of TME and cancer compartments and how they relate to sensitivity to different neoadjuvant treatments in 33 bladder cancer patients from the DUTRENEO trial. In conclusion, our findings may improve our understanding of tumor ecology and help identify new drug biomarkers.

Objective: To examine the role of noninvasive testing (NIT) before invasive coronary angiography (ICA) by evaluating the association between a positive myocardial perfusion imaging (MPI) or computed tomography angiography (CTA) result and the decision to perform coronary revascularization. Patients and Methods: We screened all patients who received ICA between August 1, 2015, and July 31, 2019, and identified those who received MPI or CTA within the preceding 12 months. We considered MPI to be a positive result if it found moderate or severe ischemia in a specific coronary territory and CTA to be a positive result if it identified a stenosis greater than 50% in any major coronary artery. Results: Of the 17,181 individual procedures, 2183 were included. Positive CTA had an odds ratio (OR) of 2.68 (95% CI, 1.82-3.94) for revascularization and positive MPI an OR of 1.29 (95% CI, 1.07-1.56). Overall sensitivity for CTA in the prediction of revascularization was 80.4% (95% CI, 75.7%-84.6%), with vessel-level sensitivity ranging from 57.3% (95% CI, 47.5%-66.7%) to 71.8% (95% CI, 65.8%-77.4%). Overall sensitivity of MPI was 48.2% (95% CI, 44.7%-51.7%), with territory-specific sensitivity ranging from 33.7% (95% CI, 29.9%-37.7%) to 36.5% (95% CI, 32.6%-40.6%). Overall specificity for CTA was low, at 39.5% (32.9%-46.3%), but higher when evaluating at the vessel level, ranging from 60.3% (95% CI, 54.5%-66.0%) to 83.5% (95% CI, 79.6%-86.9%). Overall specificity for MPI was 58.1% (95% CI, 54.9%-61.3%), with territory-specific specificity ranging from 78.6% (95% CI, 76.1%-80.9%) to 78.9% (95% CI, 76.5%-81.3%). Conclusion: In this population of patients referred for ICA, positive CTA was more closely associated with revascularization than MPI. Further studies are necessary to determine the role of NIT before ICA.

ABSTRACT Information processing speed (IPS) evaluates the time at which a person reacts to a stimulus. The Wechsler for Adults-III (WAIS-III) includes this domain in the digit symbol test (DS-T). Objective: The aim of this study was to validate a new screening test that could measure the IPS in association with the individual’s age and scholarship. Methods: A new instrument to measure the IPS was constructed, automatic cashier test (AC-T), and for its validation, the DS-T was also carried out. Results: The media of time use in the ACT was 12.3 s; the media of hits in the DS-T was 38.8, with a p

Lupus nephritis (LN), present in 30%–50% of systemic lupus erythematosus (SLE) patients, often necessitates standard immunosuppressive therapy (glucocorticoids, MMF, CYC) as suggested by the European League Against Rheumatism/European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) and Kidney Disease Improving Global Outcomes (KDIGO) guidelines. However, a subset of subjects remains refractory. Recent findings suggested the efficacy of targeting CD38-long-lived plasma cells in LN and SLE refractory to standard treatment. However, previous experiences were limited to adult patients and described different therapeutical schemes based on daratumumab, with the addition or absence of belimumab. Moreover, the minimal effective dose of daratumumab has yet to be fully defined. In this report, we describe two cases of juvenile-onset refractory LN/SLE successfully managed with a combination of a single infusion of rituximab (targeting CD20 on B cells) and daratumumab (targeting CD38 on long-lived plasma cells), unlike prior regimens requiring prolonged daratumumab infusions. Our approach was safe and effective and may potentially reduce adverse effects and costs, providing a novel therapeutic option for juvenile refractory LN.

Thrips tabaci is the main thrips species affecting onion and related species. It is a cryptic species complex comprising three phylogenetic groups characterized by different reproductive modes (thelytoky or arrhenotoky) and host plant specialization. Thrips tabaci populations vary widely in genetic diversity, raising questions about the factor(s) that drive this diversity. We investigated the genetic diversity, reproductive mode, and heteroplasmy frequency in T. tabaci populations from different Allium spp fields in six locations in the Netherlands in 2021 and at two locations from the North and South of Uruguay over three years to unravel how the diversity is structured in the populations and if changes can be associated with weather variables. The thrips populations from each location studied were characterized by sequencing 33 individuals per sampling using the cytochrome oxidase subunit I (COI) gene. The reproductive mode was determined using specific primers and a phylogenetic analysis. Daily data for the weather variables was obtained from agrometeorological experimental stations located in the Uruguayan sampled crop fields. The diversity, reproductive mode, and heteroplasmy of T. tabaci populations in onion crops exhibited significant year-to-year variation depending on the location. Changes in the relative frequency of each reproductive mode in populations are associated with weather variables: precipitation, temperature, number of frosts, and relative humidity. Heteroplasmy frequency was associated with the same weather variables except temperature. In Uruguay and the Netherlands, T. tabaci thelytokous haplotype H1 was the most common, showing different heteroplasmy levels within and between the populations. In the field populations, a high frequency of heteroplasmic H1 individuals was associated with low precipitation, while all H1 individuals were also associated with high temperature and high relative humidity. In Uruguay, heteroplasmy was associated with arrhenotokous T. tabaci haplotypes, which were highly common in the North, pointing at specific adaptations leading to a faster population build-up. All this information may be instrumental for designing more precise integrated pest management techniques in both conventional and organic production.

Introduction The prevention of diabetic foot ulcer (DFU) involves the classification of risk, systemic care, regular examinations, foot care, therapeutic education and adjunct treatments. Photobiomodulation (PBM) has been successfully administered for the healing of DFU and its preventive effects have drawn the interest of researchers.Methods and analysis The purpose of the study is to assess the effect of PBM for the prevention of DFU through a randomised, controlled, double-blind, clinical trial. Individuals from 18 to 75 years of age of both sexes with type 2 diabetes mellitus (DM) at moderate to high risk of developing DFU will be randomly allocated to two groups of 32 participants each. The PBM group will wear a boot with 1344 light-emitting diodes (LEDs)—504 with a wavelength of 660 nm located on the sides of the boot (28.5 mW, 10 J per LED), 504 with a wavelength of 850 nm also on the sides of the boot (23 mW, 8 J per LED), 168 with a wavelength of 660 nm on the base of the boot (28.5 mW, 10 J per LED) and 168 with a wavelength of 850 nm also on the base of the boot (23 mW, 8 J per LED). The boot will be worn once a day for 6 min over 60 days and the participants will also receive therapeutic education. The control group will wear a non-therapeutic LED boot (sham) under the same conditions and will also receive therapeutic education. Assessments will be performed at the beginning of the study, after 30 days (clinical examination) and after 60 days (clinical examination, assessment of peripheral neuropathy (PN) and peripheral artery disease (PAD), blood and urine examinations and quality of life).Ethics and dissemination This protocol received approval from the Human Research Ethics Committee of Nove de Julho University and the Mandaqui Hospital Complex (certificate number: 66098522.0.3001.5511; final approval date: 22 June 2023). The findings will be published in a peer-reviewed journal.Trial registration number NCT06353568, ClinicalTrials.gov.

Abstract The advent of bioprinting has enabled the creation of precise three‐dimensional (3D) cell cultures suitable for biomimetic in vitro models. In this study, we developed a novel protocol for 3D printing methacrylated collagen (ColMa, or PhotoCol®) combined with tendon stem/progenitor cells (hTSPCs) derived from human tendon explants. Although pure ColMa has not previously been proposed as a printable hydrogel, this paper outlines a robust and highly reproducible pipeline for bioprinting this material. Indeed, we successfully fabricated a 3D bioengineered scaffold and cultured it for 21 days under perfusion conditions with medium supplemented with growth/differentiation factor‐5 (GDF‐5). This bioprinting pipeline and the culture conditions created an exceptionally favorable 3D environment, enabling the cells to proliferate, exhibit tenogenic behaviors, and produce a new collagen type I matrix, thereby remodeling the surrounding environment. Indeed, over the 21‐day culture period under perfusion condition, tenomodulin expression showed a significant upregulation on day 7, with a 2.3‐fold increase, compared to days 14 and 21. Collagen type I gene expression was upregulated nearly 10‐fold by day 14. This trend was further confirmed by western blot analysis, which revealed a statistically significant difference in tenomodulin expression between day 21 and both day 7 and day 14. For type I collagen, significant differences were observed between day 0 and day 21, as well as between day 0 and day 14, with a p‐value of 0.01. These results indicate a progressive over‐expression of type I collagen, reflecting cell differentiation towards a proper tenogenic phenotype. Cytokines, such as IL‐8 and IL‐6, levels peaked at 8566 and 7636 pg/mL, respectively, on day 7, before decreasing to 54 and 46 pg/mL by day 21. Overall, the data suggest that the novel ColMa bioprinting protocol effectively provided a conducive environment for the growth and proper differentiation of hTSPCs, showcasing its potential for studying cell behavior and tenogenic differentiation.

BACKGROUND: There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer. Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for pancreatic cancer. METHODS: Data from genome-wide association studies (GWAS) within the Pancreatic Cancer Cohort Consortium (PanScan; cases n = 5,090, controls n = 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n = 4,163, controls n = 3,792) were analyzed. We used data on 68 genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separately to predict genetic heritability of NAFLD. We then assessed the relationship between each of the four MR methods and pancreatic cancer risk, using logistic regression to calculate ORs and 95% confidence intervals (CI), adjusting for PC risk factors, including obesity and diabetes. RESULTS: No association was found between genetically predicted NAFLD and pancreatic cancer risk in the PanScan or PanC4 samples [e.g., PanScan, IVW OR, 1.04; 95% confidence interval (CI), 0.88-1.22; MR-Egger OR, 0.89; 95% CI, 0.65-1.21; PanC4, IVW OR, 1.07; 95% CI, 0.90-1.27; MR-Egger OR, 0.93; 95% CI, 0.67-1.28]. None of the four MR methods indicated an association between genetically predicted NAFLD and pancreatic cancer risk in either sample. CONCLUSIONS: Genetic predisposition to NAFLD is not associated with pancreatic cancer risk. IMPACT: Given the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and pancreatic cancer might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and pancreatic cancer.