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Two human induced pluripotent stem cell lines, LEIi021-A and LEIi021-B, were derived from dermal fibroblasts from a healthy control subject from an Australian Aboriginal family with retinitis pigmentosa-11. Reprogramming was performed using episomal vectors expressing OCT4, SOX2, LIN28, L-MYC, KLF4 and mp53DD. Pluripotency markers were expressed in both LEIi021-A and LEIi021-B lines. The two cell lines displayed normal karyotypes and demonstrated the ability to differentiate into embryoid bodies with the three primary germ layers and retinal pigment epithelial cells.

There is limited evidence on heterogenous co-developmental trajectories of internalizing (INT) and externalizing (EXT) problems from childhood to adolescence and predictors of these joint trajectories. We utilized longitudinal data from Raine Study participants (n = 2393) to identify these joint trajectories from 5 to 17 years using parallel-process latent class growth analysis and analyze childhood individual and family risk factors predicting these joint trajectories using multinomial logistic regression. Five trajectory classes were identified: Low-problems (Low-INT/Low-EXT, 29%), Moderate Externalizing (Moderate-EXT/Low-INT, 26.5%), Primary Internalizing (Moderate High-INT/Low-EXT, 17.5%), Co-occurring (High-INT/High-EXT, 17%), High Co-occurring (Very High-EXT/High-INT, 10%). Children classified in Co-occurring and High Co-occurring trajectories (27% of the sample) exhibited clinically meaningful co-occurring problem behaviors and experienced more adverse childhood risk-factors than other three trajectories. Compared with Low-problems : parental marital problems, low family income, and absent father predicted Co-occurring and High Co-occurring trajectories; maternal mental health problems commonly predicted Primary Internalizing, Co-occurring , and High Co-occurring trajectories; male sex and parental tobacco-smoking uniquely predicted High Co-occurring membership; other substance smoking uniquely predicted Co-occurring membership; speech difficulty uniquely predicted Primary Internalizing membership; child's temper-tantrums predicted all four trajectories, with increased odds ratios for High Co-occurring (OR = 8.95) and Co-occurring (OR = 6.07). Finding two co-occurring trajectories emphasizes the importance of early childhood interventions addressing comorbidity. [ABSTRACT FROM AUTHOR]

Two human induced pluripotent stem cell lines, LEIi021-A and LEIi021-B, were derived from dermal fibroblasts from a healthy control subject from an Australian Aboriginal family with retinitis pigmentosa-11. Reprogramming was performed using episomal vectors expressing OCT4, SOX2, LIN28, L-MYC, KLF4 and mp53DD. Pluripotency markers were expressed in both LEIi021-A and LEIi021-B lines. The two cell lines displayed normal karyotypes and demonstrated the ability to differentiate into embryoid bodies with the three primary germ layers and retinal pigment epithelial cells. [ABSTRACT FROM AUTHOR]

Process modeling of ultrasonic additive manufacturing (UAM) is critical for optimizing process settings with minimal experimental trials. In this research, a parameter termed weld quality (Qw) is formulated based on hardness and process settings to predict the shear strength of aluminum alloy 6061 (AA6061) UAM weld interfaces between similar and dissimilar tempers. Four AA6061 tempers are investigated: O (annealed), H18 (cold rolled with 75% thickness reduction), T4 (solution heat treated and naturally aged), and T6 (solution heat treated and artificially aged). Shear samples quantify the shear strength at foil-to-foil and baseplate-to-foil interfaces, with near-gapless bonding observed. The Qw parameter linearly correlates with shear strength measurements, achieving a coefficient of determination ( R 2 ) of 91.18%. [ABSTRACT FROM AUTHOR]

This NOTION-2 sub-study revealed distinct outcomes for transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in low surgical risk patients aged ≤ 70 years with a tricuspid or bicuspid aortic valve stenosis (AS). One year after intervention, the risk of death, stroke or rehospitalization in patients with tricuspid AS was similar after TAVR when compared to SAVR (absolute risk difference: -2.0%; 95% confidence interval (CI): -11.8% to 7.7%) Conversely, in patients with bicuspid AS, TAVR was associated with a significantly higher risk of adverse outcomes (absolute risk difference: 13.8%; 95% CI: 1.2% to 26.3%). These analyses are exploratory, but highlight the importance of tailoring the intervention to the patient's clinical risk profile, life expectancy, native aortic valve morphology and the anticipated risks associated with TAVR or SAVR. Trial Registration number: ClinicalTrials.gov NCT02825134., Competing Interests: Declaration of competing interest Savontaus, M. received honoaria from Medtronic, Boston Scientific and Edwards LifeSciences; Angerås, O. received honoraria from Medtronic, Abbott, Meril and support for attending meeting and travel from Meril, Abbott; Rück, A. received grants, consulting fees and participated in data safety monitoring board with Boston Scientific; Christiansen, E. received honoaraia from Meril; Predergast, B is in advisory Board Anteris, Trial Steering Committee Medtronic and Data Safety Monitoring Committee Valvosoft; Leon M has recieved grant from Edwards Lifesciences, Abbott Vascular and Medtronic, consultant fees from Foldax and Anteris, is in data saftemonitoring board with Medtronic, have leadership role in Heart Valve Collaboratory and stocks in Pi-Cardia; Søndergaard, L. is employee at Abbott; De Baclker, O. received consulting fees from Abott, Boston Scientific, Medtronic, (Copyright © 2025. Published by Elsevier Inc.)

Endothelial cells (ECs) migrate, sprout, and proliferate in response to (lymph)angiogenic mitogens, such as vascular endothelial growth factors. When ECs reach high confluency and encounter spatial confinement, they establish mature cell-cell junctions, reduce proliferation, and enter a quiescent state through a process known as contact inhibition. However, EC quiescence is modulated not only by spatial confinement but also by other mechano-environmental factors, including blood or lymph flow and extracellular matrix properties. Changes in physical forces and intracellular signaling can disrupt contact inhibition, resulting in aberrant proliferation and vascular dysfunction. Therefore, it is critical to understand the mechanisms by which endothelial cells regulate contact inhibition. While contact inhibition has been well studied in blood endothelial cells (BECs), its regulation in lymphatic endothelial cells (LECs) remains largely unexplored. Here, we review the current knowledge on extrinsic stimuli and intrinsic molecular pathways that govern endothelial contact inhibition and highlight nuanced differences between BECs and LECs. Furthermore, we provide perspectives for future research on lymphatic contact inhibition. A deeper understanding of the BEC and LEC-specific pathways underlying contact inhibition may enable targeted modulation of this process in blood or lymphatic vessels with relevance to lymphatic or blood vascular-specific disorders., (© 2025 The Author(s).)

Wastewater surveillance has played a pivotal role in monitoring SARS-CoV-2 transmission worldwide. However, developing and implementing the methods underpinning these programmes in regions with prolonged periods of low community transmission has proven challenging. In Victoria, Australia, wastewater surveillance provided early warning of unknown community infections and informed timely public health decisions to limit their spread when case numbers were low. To achieve this, we developed a methodological approach sensitive to extremely low viral loads and could readily identify false positives within short turnaround times. Here, we describe the successful development, implementation, and evaluation of analytic methods using Reverse Transcriptase Quantitative Polymerase Chain Reaction (RT-qPCR) and amplicon sequencing in tandem with CRISPR DETECTR in an ongoing, large-scale surveillance programme to detect SARS-CoV-2 in wastewater in Victoria, Australia. Our study covers ten months, from July 2020 to April 2021, and includes all state-wide health districts and prolonged periods with no known, active community cases among the ∼6.7 million population., Competing Interests: The authors declare there is no conflict., (© 2025 The Authors This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits copying, adaptation and redistribution, provided the original work is properly cited (http://creativecommons.org/licenses/by/4.0/).)

Background: The LIMERIC study has proven that colonoscopy-assisted laparoscopic wedge resection effectively and safely removes benign colonic lesions unsuitable for endoscopic removal, thereby avoiding the need for major surgery., Objective: To evaluate the impact of colonoscopy-assisted laparoscopic wedge on health-related quality of life of patients who participated in the LIMERIC study., Design: Prospective multicenter study., Settings: The LIMERIC study was performed between 2016 and 2020 in 13 Dutch hospitals. Five-level EuroQoL 5-dimension questionnaires were administered at baseline and 3 months after the procedure., Patients: Patients with incomplete pre- or postoperative questionnaires or those undergoing combined interventions were excluded from the intention-to-treat analysis. Those for whom CAL-WR was not feasible or who underwent completion surgery were excluded from the per-protocol analysis., Intervention: Colonoscopy-assisted laparoscopic wedge for either 1) colon polyp unsuitable for endoscopic resection; 2) nonlifting residual or recurrent polyp within scar tissue after previous polypectomy; or (3) Rx/R1 endoscopic removal of a low-risk pT1 colon carcinoma., Main Outcome Measures: Three-month health-related quality of life., Results: Colonoscopy-assisted laparoscopic wedge did not affect health-related quality of life in the per-protocol analysis (n = 56) or in the intention-to-treat analysis (n = 67). The majority of patients reported no change in health status (57%). No significant differences were observed in the distribution of responses across all 5 dimensions before and after colonoscopy-assisted laparoscopic wedge. Patients'EuroQoL self-rated visual analog scale scores were also unaffected by a colonoscopy-assisted laparoscopic wedge, with a median score of 82.5 at baseline and 80 after surgery in the per-protocol analysis ( p = 0.63)., Limitations: Solely a patient-reported outcome measure evaluating global health-related quality of life was used, rather than one specifically assessing disease-related quality of life, such as the quality of life questionnaire colorectal cancer module 29., Conclusions: Colonoscopy-assisted laparoscopic wedge has no significant impact on the health-related quality of life in patients with benign colonic lesions and should therefore be considered before major surgery is performed. See Video Abstract., Reseccin Laparoscpica En Cua Asistida Por Colonoscopia Para Lesiones Colnicas Impacto En La Calidad De Vida Resultados Del Estudio Limeric: ANTECEDENTES:El estudio LIMERIC ha demostrado que la resección laparoscópica en cuña asistida por colonoscopia elimina de forma eficaz y segura las lesiones colónicas benignas inadecuadas para la extirpación endoscópica, evitando así la necesidad de cirugía mayor.OBJETIVO:Evaluar el impacto de la cuña laparoscópica asistida por colonoscopia en la calidad de vida relacionada con la salud de los pacientes que participaron en el estudio LIMERIC.DISEÑO:Estudio multicéntrico prospectivo.ENTORNO:El estudio LIMERIC se realizó entre 2016 y 2020 en 13 hospitales holandeses. Se administraron cuestionarios EQ-5D-5L al inicio y 3 meses después del procedimiento.PACIENTES:Los pacientes con cuestionarios pre o postoperatorios incompletos o aquellos sometidos a intervenciones combinadas fueron excluidos del análisis por intención de tratar. Aquellos en los que la CAL-WR no era factible o que se sometieron a cirugía de finalización fueron excluidos del análisis por protocolo.INTERVENCIÓN:Cuña laparoscópica asistida por colonoscopia para (1) pólipo de colon no apto para resección endoscópica; (2) pólipo residual o recidivante no elevable dentro de tejido cicatricial tras polipectomía previa; o (3) extirpación endoscópica Rx/R1 de un carcinoma de colon pT1 de bajo riesgo.MEDIDAS DE RESULTADO PRINCIPALES:Calidad de vida relacionada con la salud a los tres meses.RESULTADOS:La cuña laparoscópica asistida por colonoscopia no afectó a la calidad de vida relacionada con la salud en el análisis por protocolo (n = 56), ni en el análisis por intención de tratar (n = 67). La mayoría de los pacientes no informaron ningún cambio en su estado de salud (57%). No se observaron diferencias significativas en la distribución de las respuestas en las 5 dimensiones antes y después de la cuña laparoscópica asistida por colonoscopia. La EQ-VAS autoevaluada de los pacientes tampoco se vio afectada por la cuña laparoscópica asistida por colonoscopia, con una puntuación media de la VAS de 82,5 al inicio y 80 después de la cirugía en el análisis por protocolo (p = 0,63).LIMITACIONES:Se utilizó únicamente una medida de resultados comunicada por el paciente que evaluaba la calidad de vida global relacionada con la salud, en lugar de una que evaluara específicamente la calidad de vida relacionada con la enfermedad, como el QLQ-CR29.CONCLUSIONES:La cuña laparoscópica asistida por colonoscopia no tiene un impacto significativo en la calidad de vida relacionada con la salud en pacientes con lesiones colónicas benignas y, por lo tanto, debe considerarse antes de realizar una cirugía mayor. (Traducción-Dr. Aurian Garcia Gonzalez )., (Copyright © The ASCRS 2024.)

Objective: Hurried encounters in clinical settings contribute to dissatisfaction among both patients and clinicians and may indicate and contribute to low-quality care. We sought to identify patient- or clinician-reported instruments concerning this experience of time in clinical encounters., Methods: We searched multiple databases from inception through July 2023. Working in duplicate without restrictions by language or clinical context, we identified published instruments or single items measuring perceptions of time adequacy in clinical encounters. We characterized these by time domain (perceived duration or pace of the encounter), responder (patient or clinician), and reference (experience of care in general or of a particular encounter)., Results: Of the 96 instruments found, none focused exclusively on perception of time adequacy in clinical encounters. Nonetheless, these instruments contained 107 time-related items. Of these, 81 items (77 %) measured the perception of the encounter duration, assessing whether there was adequate consultation time overall or for specific tasks (e.g., listening to the patient, exploring psychosocial issues, formulating the care plan). Another 19 (18 %) assessed encounter pace, and 7 (7 %) assessed both duration and pace. Pace items captured actions perceived as rushed or hurried or the perception that patients and clinicians felt pressed for time or rushed. Patients were the respondents for 76 (71 %) and clinicians for 24 (22 %) items. Most patient-reported items (48 of 76) referred to the patient's general care experience., Conclusion: There are existing items to capture patient and clinician perceptions of the duration and/or pace of clinical encounters. Further work should ascertain their ability to identify hurried consultations and to detect the effect of interventions to foster unhurried encounters., Practice Implications: The available items assessing patient and clinician perceptions of duration and pace can illuminate the experience of time adequacy in clinical encounters as a target for quality improvement interventions. These items may capture unintended consequences on perceived time for care of interventions to improve healthcare access and efficiency., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background:  Piecemeal endoscopic mucosal resection (EMR) of large (≥ 20 mm) nonpedunculated colorectal polyps (LNPCPs) is succeeded by a 6-month surveillance endoscopy to evaluate the post-EMR scar for recurrence. Data from expert centers suggest that routine tattoo placement and scar biopsies can be omitted, but data from community hospitals are lacking., Methods:  The agreement between optical assessment and histological confirmation by routine biopsies was evaluated in a post-hoc analysis of the STAR-LNPCP study (NTR7477), containing prospective data on 6-month post-EMR scar assessments in 30 Dutch community hospitals (October 2019 to May 2022). A standardized protocol was followed for documentation of optical characteristics, imaging, and biopsy of the post-EMR scar. RESULTS : In 1277 post-EMR scar assessments, identification of the scar was achieved in 1215/1277 (95 %). Tattoo placement did not influence scar identification. Scar biopsy was performed in 1050/1215 cases (86 %). Recurrences were seen in 200/1050 cases (19 %). There was good agreement between optical assessment of recurrence and histological confirmation (Cohen's kappa 0.78 [95 %CI 0.73-0.83]). The negative and positive predictive values were 98 % (95 %CI 97 %-99 %) and 74 % (95 %CI 68 %-80 %), respectively. A higher false-positive rate was seen after prior use of clips (11 % vs. 5 %; P  = 0.02). Dedicated endoscopists identified the scar more often (96 % vs. 88 %; P  < 0.001), and showed a lower optical recurrence miss rate (1 % vs. 3 %; P  = 0.11) compared with nondedicated endoscopists. CONCLUSION : Based on this multicenter community hospital study, routine tattoo placement and scar biopsies of the post-EMR scar can be omitted. Assessment of post-EMR scars by dedicated endoscopists is advised., Competing Interests: P. Siersema received grants or speaker’s fees from Pentax Japan, The E-Nose Company The Netherlands, Microtech China, Lucid Diagnostics USA, Magentiq Eye Israel, Norgine UK/The Netherlands, and Motus GI USA. M. Pellisé has received speaker’s fees from Norgine Iberia (2018–2023), Casen Recordati (2016 – 2019), Olympus (2018, 2022), Jansen (2018), Medtronic (2022), Fujifilm (2022); a consultancy fee GI Supply (2019), Fujifilm Europe (2022) and research funding from Fujifilm (2019–2021), Casen Recordati (2020); Ziuz (2021); 3-DMatrix (2021); her department has received loan material from Fujifilm (2017– ongoing), a consultancy service with Olympus (2022-ongoing); She is Board member of ESGE and AEG; and has received a fee from Thieme as an Endoscopy Co-Editor (2015–2021). She has shared actions of MiWendo. M. Bourke received research support for ethics-approved studies from Boston Scientific, Cook Medical, and Olympus Medical. A. Masclee received research grants from the Dutch Cancer Society (KWF) and the Dutch Organization for Health Research and Innovation (ZonMW). L. Moons acts as a consultant for Boston Scientific.The other authors disclose no competing interests., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Amyloid-targeting therapy has recently become widely available in the U.S. for the treatment of patients with symptomatic mild Alzheimer's disease (AD). At present, there are no biomarkers that have been clinical validated to assess treatment response in routine clinical practice; longitudinal amyloid PET could play a role but is not cost effective. This report presents a case series of six patients with AD, whose amyloid positivity was confirmed by PET or CSF biomarkers, who underwent baseline and longitudinal arterial spin-labeling magnetic resonance imaging (ASL-MR) as part of FDA-mandated, clinical standard-of-care, non-contrast MR monitoring to assess for amyloid-related imaging abnormalities (ARIA). We and others have previously reported that ASL-MR can screen for neurodegenerative disease, as a proxy for FDG-PET, and can be easily added on as a cost-effective, repeatable method to monitor post-therapy changes. This series highlights varied cerebral blood flow (CBF) changes in response to lecanemab therapy. For instance, Cases 1, 3, and 5 showed increased CBF after multiple infusions, with subjective cognitive improvement in Case 1 and improved MoCA scores in Case 3. Case 2 showed improved CBF initially before the 5 th infusion, but this returned to baseline on the subsequent study, with no cognitive improvement over the course of therapy. Cases 4 and 6 have demonstrated no significant changes in regional CBF thus far on therapy, with cognitive decline in Case 4. This case series underscores the potential utility of ASL-MR as an adjunct sequence to current imaging protocols to monitor treatment response to anti-amyloid therapy.ABBREVIATIONS: ASL-MR = arterial spin-labeling magnetic resonance imaging; MRI = magnetic resonance imaging; CBF = cerebral blood flow; AD = Alzheimer's disease; PET = positron emission tomography; CSF = cerebrospinal fluid; FDG = fluorodeoxyglucose., Competing Interests: The remaining authors declare no conflicts of interest related to the content of this article., (© 2025 by American Journal of Neuroradiology.)

Background & Aims: Colonoscopy-based surveillance to prevent colorectal cancer (CRC) causes substantial burden for patients and health care. Stool tests may help to reduce surveillance colonoscopies by limiting colonoscopies to individuals at increased risk of advanced neoplasia., Methods: This cross-sectional observational study included individuals aged 50-75 years with surveillance indication. Before bowel preparation, participants collected samples for a multitarget stool DNA test and 2 fecal immunochemical tests (FITs). Test accuracy was calculated for all surveillance indications. For the post-polypectomy indication only, which is the most common and is associated with a relatively low CRC risk, long-term impact of stool-based surveillance was evaluated with the Adenoma and Serrated Pathway to Colorectal Cancer (ASCCA) model. Stool-based strategies were simulated to tune each test's positivity threshold to obtain strategies at least as effective as colonoscopy surveillance., Results: There were 3453 individuals with results for all stool tests and colonoscopy; 2226 had previous polypectomy, 1003 had previous CRC, and 224 had a familial risk. Areas under the receiver operating characteristic curve for advanced neoplasia were 0.72 (95% CI, 0.69-0.75) for the multitarget stool DNA test, 0.61 (95% CI, 0.58-0.64) for the FIT OC-SENSOR (Eiken Chemical Co, Tokyo, Japan) and 0.59 (95% CI, 0.56-0.61) for the FIT FOB-Gold (Sentinel, Milan, Italy). Stool-based post-polypectomy surveillance strategies at least as effective as colonoscopy surveillance reduced the number of colonoscopies by 15%-41% and required 5.6-9.5 stool tests over a person's lifetime. Multitarget stool DNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs., Conclusions: This study found that stool-based post-polypectomy surveillance strategies can be safe and cost-effective, with potential to reduce the number of colonoscopies by up to 41%., Clinicaltrials: gov, Number: NCT02715141., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the dimensional stability over time of additively manufactured surgical templates, fabricated by different resins, and stored by different methods., Materials and Methods: Using a 3D printer with DLS technology and two different resins (Surgical Guide (SG)-WhipMix and Key Guide (KG)-KeystoneIndustries), 96 surgical guides were additively manufactured. The guides were stored in three different environments: directly exposed to sunlight (S 1 ), in normal interior room conditions (S 2 ), and in darkness (S 3 ). The guides were digitally scanned immediately after fabrication and post-processing, and after 1, 3, and 6 months of storage. For each group, the mean deviation of the root mean square (RMS) between guide's intaglio surface, as well as the axial deviation between sleeves' housings were calculated., Results: The mean axial variations of angular axis deviation of sleeves' housings ranged between 0.09° and 3.99°. The mean deviation of the RMS discrepancy in guide's intaglio ranged from 0.1 to 0.18 mm. Variations were significant (p < 0.001) only for the S 1 group and only for SG material. After 3 months, an additional storage time of 3 months did not have any further effect on dimensional stability., Conclusions: Within the limitations of the present study, storage time of a surgical guide for up to 3 months after manufacturing, as well as printing material can significantly affect surgical guide's dimensional stability, when they are exposed to direct or indirect sunlight conditions. Storage of guides in a dark environment is recommended in order to avoid an additional source of error in computer-guided surgery workflows., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The effectiveness of fungicides to control foliar fungal crop diseases is being diminished by the increasing spread of resistance to fungicides. One approach that may help to maintain efficacy is remediation of resistant populations by sensitive ones. However, the success of such approaches can be compromised by re-incursion of resistance through aerial spore dispersal, although knowledge of localized gene flow is lacking. Here, we report on a replicated mark-release-recapture field experiment with several treatments set up to study spore-dispersal-mediated gene flow of a mutated allele that confers demethylase inhibitor resistance in Pyrenophora teres f. teres ( Ptt ). Artificial inoculation of the host, barley ( Hordeum vulgare ), was successful across the 12-ha trial, where the introduced sensitive and resistant populations were, respectively, 6- and 13-fold the DNA concentration of the native Ptt population. Subsequent disease pressure remained low, which hampered spread of the epidemic to such an extent that gene flow was not detected at, or beyond, 2.5 m from source points. In the absence of gene flow, plots were assessed for treatment effects; fungicide applied to populations that contained 14.3% of allele mutation increased in frequency to 24.5%, whereas sensitive populations had no change in structure. Untreated controls of the native Ptt population remained genetically stable, yet untreated controls that were inoculated with sensitive Ptt had half the resistance frequency of the native population structure. The trial demonstrates the potential for management to remediate fungicide-resistant pathogen populations, where localized gene flow is minimal, to safeguard chemical crop protection into the future., Competing Interests: The author(s) declare no conflict of interest.