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Competing Interests: Conflicts of interest None disclosed.

Objective: To assess the impact of below-benchmark (95%-100%) donor-oocyte survival rates on vitrification/warming in the laboratory and clinical outcomes of recipient cycles., Design: Retrospective cohort study., Subjects: We analyzed 12,690 vitrified-warmed donor-oocyte recipient cycles performed from 2018-2022., Exposure: All cycles analyzed used exclusively vitrified/warmed donor oocytes. The cycles were grouped according to the survival rate experienced: benchmark 95%-100%; competence 85%-95%; below competence 70%-85%; poor 50%-70%; and very poor <50%., Main Outcome Measures: The primary endpoint of the study was the total usable blastocyst rate per 2 pronuclear (2PN) zygote. Secondary endpoints were the fertilization rate, the live birth rate after the first single blastocyst transfer, and the cumulative live birth rate., Results: The mean number of warmed oocytes per intracytoplasmic sperm injection (ICSI) cycle was 11.4 ± 3.2, with a mean survival rate of 89.1%. More oocytes per cycle were consumed in the lower survival groups, yet the total number of oocytes available for ICSI was smaller in the below-competence, poor, and very poor survival groups. The total usable blastocyst rate was lower in the lower survival groups (benchmark: 48.9%; competence: 47.0%, below competence: 46.0%; poor: 43.6%; and very poor: 43.6%), as well as the fertilization rates (benchmark: 76.8%; competence: 76.6%, below competence: 75.6%; poor: 74.7%; and very poor:75.5%). The adjusted relative risk (aRR) of live birth rate of the first embryo transferred was equal to the benchmark survival group in all the lower survival groups (benchmark: 40.9%; competence: aRR = 0.986, 95% confidence interval [CI]: 0.931-1.045; below-competence: aRR = 0.992, 95% CI: 0.929-1.059; poor: aRR = 1.103, 95% CI: 1.009-1.207; and very poor: aRR = 1.169, 95% CI: 0.963-1.419). The cumulative live birth rate decreased in lower survival groups compared with benchmark survival (benchmark: 79.2%; competence: aRR = 0.988, 95% CI: 0.961-1.015; below competence: aRR = 0.911, 95% CI: 0.880-0.944; poor: aRR = 0.802, 95% CI: 0.757-0.851; and very poor: aRR = 0.793, 95% CI: 0.693-0.907). The lower cumulative rates maintained in a subanalysis with equal metaphase-II available for ICSI (benchmark: 69.5%; competence: aRR = 0.909, 95% CI: 0.827-1.000; below competence: aRR = 0.942, 95% CI: 0.848-1.046; poor: aRR = 0.833, 95% CI: 0.7386-0.941; and very poor: aRR = 0.873, 95% CI: 0.695-1.097) CONCLUSION: Lower donor-oocyte cryo-survival rates have a moderate negative impact on the blastocyst utilization rate per 2PN zygote, fertilization rate, and the cumulative live birth rates of a donation cycle, even after adjusting for equal metaphase-II oocytes available for ICSI. Nonetheless, the surviving oocytes of a cohort seem to maintain a high competence level, with very similar laboratory outcomes, irrespective of the cohort's survival rates, as well as equal implantation potential of the resulting blastocysts., Competing Interests: Declaration of Interests M.G. reports honoraria from Merck GmBH outside the submitted work. I.G. has nothing to disclose. J.R. has nothing to disclose. A.P.S. has nothing to disclose. N.G. has nothing to disclose. J.L.M. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Artificial intelligence(AI)-based methods have been extensively used for the detection and management of various common retinal conditions, but their targeted development for inherited retinal diseases (IRD) is still nascent. In the context of limited availability of retinal subspecialists, genetic testing and genetic counseling, there is a high need for accurate and accessible diagnostic methods. The currently available AI studies, aiming for detection, classification, and prediction of IRD, remain mainly retrospective and include relatively limited numbers of patients due to their scarcity. We summarize the latest findings and clinical implications of machine-learning algorithms in IRD, highlighting the achievements and challenges of AI to assist ophthalmologists in their clinical practice., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 Elsevier Inc. All rights reserved.)

A comprehensive evaluation of the use of plant protection products (PPP) of the pesticide chlorantraniliprole (CAP) in soils has been done considering chemical and microbiological aspects. The study has been focused on the two most representative soil textures in greenhouse in the Southeast of Spain, clay (CS) and sandy clay loam soil (SCLS). The research has been divided into two phases, including laboratory (for 7 months) and field (for 2 months) studies to expand information on the behavior of the target pesticide in soils and their microorganisms. A combination of ultrasound-assisted QuEChERS extraction and ultra-high performance liquid chromatography with Q-Exactive-Orbitrap mass spectrometry (UHPLC-Q-Exactive-Orbitrap) was validated to determine the fate of the parent pesticide and its metabolites and has shown the great persistence characteristic of CAP in soil, with half-lives of 210 days under laboratory conditions and 86 days in the field study, fitting to first and biphasic kinetic models of dissipation, respectively. The suspect screening has allowed the additional detection of 6 metabolites in the laboratory and 2 metabolites in the field studies. The 5-bromo-N-methyl-1H-pyrazole-3-carboxamide metabolite has been detected in both laboratory and field studies, but also a previously undescribed metabolite N-methylprop-1-en-2-amine. Finally, a study of the impact of this PPP on the soil microbiota, a clear indicator of the state of an ecosystem or crop, revealed that after three months of exposure to CAP under laboratory conditions, soil microbial activities were affected, but this effect depended on soil., 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 © 2025. Published by Elsevier Ltd.)

The current approach to minimize transplant-associated complications, including graft-versus-host disease (GVHD) includes long-term pharmacological immune suppression frequently accompanied by unwanted side effects. Advances in targeted immunotherapies regulating alloantigen responses in the recipient continue to reduce the need for pan-immunosuppression. Here, in vivo targeting of the TNF superfamily receptor 25 (TNFRSF25) and the high affinity IL-2 receptor with a TL1A-Ig fusion protein and low dose IL-2, respectively, was used to pretreat recipient mice prior to allogeneic-HSCT (aHSCT). Pretreatment induced Treg expansion persisting early post-aHSCT leading to diminished GVHD and improved transplant outcomes. Expansion was accompanied by an increase in frequency of stable and functionally active Tregs as evidenced by in vitro assays using cells from major GVHD target tissues including colon, liver, and eye. Importantly, pretreatment supported epithelial cell function/integrity, a diverse microbiome including reduction of pathologic bacteria overgrowth and promotion of butyrate producing bacteria, while maintaining physiologic levels of obligate/facultative anaerobes. Notably, using a sphingosine 1-phosphate receptor agonist to sequester T cells in lymphoid tissues, we found that the increased tissue Treg frequency included resident CD69 + CD103 + FoxP3 + hepatic Tregs. In contrast to infusion of donor Treg cells, the strategy developed here resulted in the presence of immunosuppressive target tissue environments in the recipient prior to the receipt of donor allo-reactive T cells and successful perseveration of GVL responses. We posit strategies that circumvent the need of producing large numbers of ex-vivo manipulated Tregs, may be accomplished through in vivo recipient Treg expansion, providing translational approaches to improve aHSCT outcomes.

Enhancers are short DNA sequences that activate their target promoter from a distance; however, increasing the genomic distance between the enhancer and the promoter decreases expression levels. Many genes are controlled by combinations of multiple enhancers, yet the interaction and cooperation of individual enhancer elements are not well understood. Here, we developed a synthetic platform in mouse embryonic stem cells that allows building complex regulatory landscapes from the bottom up. We tested the system by integrating individual enhancers at different distances and confirmed that the strength of an enhancer contributes to how strongly it is affected by increased genomic distance. Furthermore, synergy between two enhancer elements depends on the distance at which the two elements are integrated: introducing a weak enhancer between a strong enhancer and the promoter strongly increases reporter gene expression, allowing enhancers to activate from increased genomic distances., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Functional dependence on the performance of basic activities of daily living (ADLs) is associated with increased mortality. In this study, the Barthel index and its activities discriminate long-term mortality risk, and whether changes in this index are necessary to adapt it to detect mortality risk is examined., Methods: Longitudinal study, carried out at the Orcasitas Health Center, Madrid (Spain), on the functional dependent population (Barthel ≤ 60). It included 127 people, with a mean age of 86 years (78.7% women and 21.3% men). Functional capacity was assessed using the Barthel index, and this index and each item it contains were analyzed as a test in relation to survival at three years, using tools that evaluate precision, discrimination, and calibration. The date of death was obtained from the health system., Results: Greater dependency to perform chair-to-bed transfers was associated with an increased mortality risk (HR 2.957; CI 1.678-5.211). Also, individuals with severe (HR 0.492; CI 0.290-0.865) and moderate (HR 0.574; CI 0.355-0.927) ADL dependence had a reduced mortality risk when more independent in chair-to-bed transfers. Among people with moderate ADL dependence, this percentage was 48%. Using dependence-independence for chair-to-bed transfer as a screening test for mortality, the test showed high sensitivity (0.91) and specificity (0.83), a positive likelihood ratio of 5.45, and a negative likelihood ratio of 0.11. The area under the ROC curve was 0.814 (CI 0.658-0.970; p  = 0.001), with a χ 2  = 0.235; p  = 0.889, according to the Hosmer-Lemeshow test. The concordance C index was 0.814. According to Nagelkerke's R 2 , the model explained 53.1% of the variance in survival. As a screening test, "chair-to-bed transfer" was superior to the Barthel index., Conclusion: ADL dependence for chair-to-bed transfers is an independent risk factor for mortality for any level of dependency. Therefore, a new classification of the Barthel index is proposed, in which "being dependent or requiring great assistance to perform chair-to-bed transfers" is considered severe dependence, even when the total score obtained via the Barthel Index is ≥40. We propose its use as a screening test in parallel to the Barthel index. The study suggests that the Barthel Index may have limitations in adequately discriminating mortality risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Martín Moreno, Martínez Sanz, Martín Fernández, Guerra Maroto, Sevillano Fuentes, Pérez Rico, Sánchez González, Fernández Gallardo, Herranz Hernando, Benítez Calderón, Calderón Jiménez, Sánchez Rodríguez, Recuero Vázquez, Alonso Samperiz, León Saiz and Marcos Guerra.)

We present a procedure to obtain histological preparations of insect cuticles for their observation in ligth microscopy. The use of EDTA (ethylendiaminetetraacetic acid), as a chelator of certain metals present in chitin, soften the tissues and allows us to cut them. The tissues were embbeding in plastic resines in two different protocols and cutted by cryostat (20-30 μm) and ultramicrotome (4 μm) respectively. This procedure, based on traditional histology products, allows us to obtain preparations observable under an optical microscope, facilitating the study of the internal structure of the cuticule, e.g. visualizing the different layers or structures such as glands or setae., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To assess the acceptance and intention to use physiological sensor shirt among older patients in healthcare, as well as to identify the factors that encourage a positive attitude towards its adoption., Methods: Cross-sectional study using questionnaires addressed to patients between 60 and 85years of age, administered via face-to-face interviews to determine intention to use a shirt with physiological sensors. The extended version of the Technology Acceptance Model (TAM) questionnaire was used in conjunction with administration of the quality of life and perceived stress scales., Results: Forty-eight patients participated in the study, 54.2% were male with a mean age of 70.5years. The mean scores for attitude towards use and intention to use were 3.9 (SD: 0.8) and 3.3 (SD: 0.8), respectively, out of a maximum of 5. The willingness to use the device was positive in 72.9% of patients The patients intending to use wearable technology (n=35) scored significantly higher than those unwilling to wear the shirt (n=13) on perceived ubiquity (P=.031), perceived ease of use (P=.002), and perceived utility (P=.007)., Conclusions: In a sample of independent older adults from the healthcare sector, a high willingness to use a shirt with physiological sensors was found. Through the TAM questionnaire, ubiquity, perceived ease of use, and perceived usefulness were identified as key factors predisposing its adoption., (Copyright © 2024 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Tianeptine is a tricyclic antidepressant (TCA) without FDA-approval that acts on dopamine and norepinephrine. It has opioid agonist activity and is increasingly being used for recreational purposes to achieve an opioid-like anxiolytic effect. This can lead to clinical addiction with subsequent withdrawal symptoms resembling symptoms of opioid withdrawal. There are limited cases detailing the management of tianeptine withdrawal., Case Summary: We present the case of a 38-year-old male with chronic tianeptine use admitted to the Intensive Care Unit for treatment of encephalopathy and vital sign changes due to intake of multiple substances and suspected tianeptine withdrawal. He reported 8 to 20 g daily use of tianeptine. He was initially managed with buprenorphine/naloxone and supportive care and reported improvement in withdrawal symptoms within three days of admission. We trialed transitioning to methadone, given possible long-term benefit due to TCA-like properties, but this was discontinued due to difficulty with access on discharge. He was provided with a bridge prescription for buprenorphine/naloxone to cover until his outpatient follow-up visit and was subsequently discharged home., Conclusion: This case demonstrates management of tianeptine withdrawal in a hospitalized patient presenting with significant daily use not reported previously in the literature.