Miracle-dz/UniFAR-FTUs huggingface dataset:
Perioperative Neurofilament Light Plasma Concentrations and Cognition before and after Cardiac Surgery: A Prospective Nested Cohort Study

Background: Neurofilament light is a marker of neuronal injury and can be measured in blood. Postoperative increases in neurofilament light have been associated with delirium after noncardiac surgery. However, few studies have examined the association of neurofilament light changes with postdischarge cognition in cardiac surgery patients, who are at highest risk for neuronal injury and cognitive decline. The authors hypothesized that increased neurofilament light (both baseline and change) would be associated with worse neuropsychological status up to 1 yr after cardiac surgery. Methods: This observational study was nested in a trial of cardiac surgery patients, in which blood pressure during bypass was targeted using cerebral autoregulation monitoring. Plasma concentrations of neurofilament light were measured at baseline and postoperative day 1. Neuropsychological testing was performed at baseline, 1 month after surgery, and 1 yr after surgery. Primary outcomes were baseline and change from baseline in a composite z-score of all cognitive tests. Results: Among 167 patients, cognitive outcomes were available in 80% (134 of 167) and 61% (102 of 167) at 1 month and 1 yr after surgery, respectively. The median baseline concentration of neurofilament light was 18.2 pg/ml (interquartile range, 13.4 to 28.1), and on postoperative day 1 was 28.5 pg/ml (interquartile range, 19.3 to 45.0). Higher baseline log neurofilament light was associated with worse baseline cognitive z-score (adjusted slope, –0.60; 95% CI, –0.90 to –0.30; P < 0.001), no change in z-score from baseline to 1 month (0.11; 95% CI, –0.19 to 0.41; P = 0.475), and improvement in z-score from baseline to 1 yr (0.56; 95% CI, 0.31 to 0.81; P < 0.001). Whereas some patients had an improvement in cognition at 1 yr and others a decline, an increase in neurofilament light from baseline to postoperative day 1 was associated with a greater decline in cognition at 1 yr. Conclusions: Higher baseline neurofilament light concentration was associated with worse baseline cognition but improvement in cognition at 1 yr. A postoperative increase in neurofilament light was associated with a greater cognitive decline at 1 yr. In an observational study of 167 cardiac surgery patients nested within a randomized controlled study of blood pressure management, higher baseline neurofilament light concentration in blood is associated with worse baseline cognition, but improvement in cognition at 1 yr. An increase in neurofilament light on postoperative day 1 is associated with a greater decline in cognition at 1 yr.
TCR-engineered iNKT cells induce robust antitumor response by dual targeting cancer and suppressive myeloid cells

Adoptive immunotherapy with T cells engineered with tumor-specific T cell receptors (TCRs) holds promise for cancer treatment. However, suppressive cues generated in the tumor microenvironment (TME) can hinder the efficacy of these therapies, prompting the search for strategies to overcome these detrimental conditions and improve cellular therapeutic approaches. CD1d-restricted invariant natural killer T (iNKT) cells actively participate in tumor immunosurveillance by restricting suppressive myeloid populations in the TME. Here, we showed that harnessing iNKT cells with a second TCR specific for a tumor-associated peptide generated bispecific effectors for CD1d- and major histocompatibility complex (MHC)–restricted antigens in vitro. Upon in vivo transfer, TCR-engineered iNKT (TCR-iNKT) cells showed the highest efficacy in restraining the progression of multiple tumors that expressed the cognate antigen compared with nontransduced iNKT cells or CD8+ T cells engineered with the same TCR. TCR-iNKT cells achieved robust cancer control by simultaneously modulating intratumoral suppressive myeloid populations and killing malignant cells. This dual antitumor function was further enhanced when the iNKT cell agonist α-galactosyl ceramide (α-GalCer) was administered as a therapeutic booster through a platform that ensured controlled delivery at the tumor site, named multistage vector (MSV). These preclinical results support the combination of tumor-redirected TCR-iNKT cells and local α-GalCer boosting as a potential therapy for patients with cancer. Description Redirecting iNKT cells against cancer cells by TCR engineering restrains immunosuppression and promotes strong antitumor responses. TCR-engineered iNKT cells Adoptive cell therapy has had success in treating various blood cancers. However, in solid tumors, most of these therapies show little efficacy due to exhaustion and poor migration to tumors. Here, Delfanti et al. leveraged natural killer T cells as an adoptive cell therapy platform, specifically producing them to express a TCR specific for a tumor-associated antigen. In mouse models, they found that these TCR-engineered iNKT robustly delayed tumor growth, leading to rejection and prolonged antitumor effects in some mice. These cells migrated well into tumors, killed tumor cells directly, and helped to shift intratumorally myeloid cells to an antitumor phenotype. Boosting TCR-engineered iNKTs with α-GalCer improved antitumor immune responses. Thus, TCR-engineered iNKT cells might be a promising therapy for patients with cancer.
Targeting deoxycytidine kinase improves symptoms in mouse models of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease driven by lymphocyte activation against myelin autoantigens in the central nervous system leading to demyelination and neurodegeneration. The deoxyribonucleoside salvage pathway with the rate‐limiting enzyme deoxycytidine kinase (dCK) captures extracellular deoxyribonucleosides for use in intracellular deoxyribonucleotide metabolism. Previous studies have shown that deoxyribonucleoside salvage activity is enriched in lymphocytes and required for early lymphocyte development. However, specific roles for the deoxyribonucleoside salvage pathway and dCK in autoimmune diseases such as MS are unknown. Here we demonstrate that dCK activity is necessary for the development of clinical symptoms in the MOG35–55 and MOG1–125 experimental autoimmune encephalomyelitis (EAE) mouse models of MS. During EAE disease, deoxyribonucleoside salvage activity is elevated in the spleen and lymph nodes. Targeting dCK with the small molecule dCK inhibitor TRE‐515 limits disease severity when treatments are started at disease induction or when symptoms first appear. EAE mice treated with TRE‐515 have significantly fewer infiltrating leukocytes in the spinal cord, and TRE‐515 blocks activation‐induced B and T cell proliferation and MOG35–55‐specific T cell expansion without affecting innate immune cells or naïve T and B cell populations. Our results demonstrate that targeting dCK limits symptoms in EAE mice and suggest that dCK activity is required for MOG35–55‐specific lymphocyte activation‐induced proliferation.
Syntactic Complexity Across Language Sampling Contexts in School-Age Children, Ages 8-11 Years.

PURPOSE Syntax has been called the structural foundation of language, as its development allows for more efficient and effective communication. Complex syntax production is known to lag in children and adolescents with language impairment. Conversation, narrative, and expository language sampling contexts are recommended tools for the comprehensive assessment of school-age children, including syntactic abilities. Despite these recommendations, few studies have examined syntactic differences obtained from these three sampling contexts in a within group sample of school-age children, (i.e., ages 8-11 years). Information about similarities and differences in syntactic measures obtained from these three sampling contexts is needed to identify the optimal sampling context(s) for eliciting complex syntax. METHOD Conversational, narrative, and expository language samples were elicited from 85 children with typically developing language ages 8;0-11;11 (years;months). Samples were transcribed and analyzed for the mean length of utterance in words and clausal density, or the number of clauses per communication unit as measured by the subordination index. RESULTS Syntactic measures differed significantly across the three sampling contexts. Namely, narrative and expository language samples elicited longer utterances and more syntactically complex language than conversation samples. Age-related differences in the syntactic measures were not detected. CONCLUSIONS Differences in syntactic measures between conversation and narrative samples and conversation and expository samples within children ages 8-11 years support use of narrative and expository contexts as the most appropriate language sampling contexts for elicitation of complex syntax in school-age children ages 8-11 years. Conversation sampling is unlikely to elicit children's capacities for complex sentence production.
Sertoli cells require TDP-43 to support spermatogenesis

Abstract TAR DNA binding protein of 43 kD (TDP-43) is an evolutionarily conserved, ubiquitously expressed transcription factor and RNA-binding protein with major human health relevance. TDP-43 is present in Sertoli and germ cells of the testis and is aberrantly expressed in the sperm of infertile men. Sertoli cells play a key role in spermatogenesis by offering physical and nutritional support to male germ cells. The current study investigated the requirement of TDP-43 in Sertoli cells. Conditional knockout (cKO) of TDP-43 in mouse Sertoli cells caused failure of spermatogenesis and male subfertility. The cKO mice showed decreased testis weight, and low sperm count. Testis showed loss of germ cell layers, presence of vacuoles, and sloughing of round spermatids, suggesting loss of contact with Sertoli cells. Using a biotin tracer, we found that the blood-testis barrier (BTB) was disrupted as early as postnatal day 24 and worsened in adult cKO mice. We noted aberrant expression of the junction proteins connexin-43 (gap junction) and N-cadherin (ectoplasmic specialization). Oil Red O staining showed a decrease in lipid droplets (phagocytic function) in tubule cross-sections, Sertoli cells cytoplasm, and in the lumen of seminiferous tubules of cKO mice. Finally, qRT-PCR showed upregulation of genes involved in the formation and/or maintenance of Sertoli cell junctions as well as in the phagocytic pathway. Sertoli cells require TDP-43 for germ cell attachment, formation and maintenance of BTB, and phagocytic function, thus indicating an essential role for TDP-43 in the maintenance of spermatogenesis. Summary Sentence Sertoli cells require the DNA/RNA binding protein TDP-43 to support spermatogenesis. In the absence of TDP-43, Sertoli cells failed to maintain germ cell attachment and the blood-testis barrier was compromised. Graphical Abstract
The role of mtDNA in oocyte quality and embryo development

The mitochondrial genome resides in the mitochondria present in nearly all cell types. The porcine (Sus scrofa) mitochondrial genome is circa 16.7 kb in size and exists in the multimeric format in cells. Individual cell types have different numbers of mitochondrial DNA (mtDNA) copy number based on their requirements for ATP produced by oxidative phosphorylation. The oocyte has the largest number of mtDNA of any cell type. During oogenesis, the oocyte sets mtDNA copy number in order that sufficient copies are available to support subsequent developmental events. It also initiates a program of epigenetic patterning that regulates, for example, DNA methylation levels of the nuclear genome. Once fertilized, the nuclear and mitochondrial genomes establish synchrony to ensure that the embryo and fetus can complete each developmental milestone. However, altering the oocyte's mtDNA copy number by mitochondrial supplementation can affect the programming and gene expression profiles of the developing embryo and, in oocytes deficient of mtDNA, it appears to have a positive impact on the embryo development rates and gene expression profiles. Furthermore, mtDNA haplotypes, which define common maternal origins, appear to affect developmental outcomes and certain reproductive traits. Nevertheless, the manipulation of the mitochondrial content of an oocyte might have a developmental advantage.
Laser Interstitial Thermal Therapy for First-Line Treatment of Surgically Accessible Recurrent Glioblastoma: Outcomes Compared With a Surgical Cohort

BACKGROUND: Laser interstitial thermal therapy (LITT) for glioblastoma (GBM) has been reserved for poor surgical candidates and deep “inoperable” lesions. We present the first reported series of LITT for surgically accessible recurrent GBM (rGBM) that would otherwise be treated with surgical resection. OBJECTIVE: To evaluate the use of LITT for unifocal, lobar, first-time rGBM compared with a similar surgical cohort. METHODS: A retrospective institutional database was used to identify patients with unifocal, lobar, first-time rGBM who underwent LITT or resection between 2013 and 2020. Clinical and volumetric lesional characteristics were compared between cohorts. Subgroup analysis of patients with lesions ≤20 cm3 was also completed. Primary outcomes were overall survival and progression-free survival. RESULTS: Of the 744 patients with rGBM treated from 2013 to 2020, a LITT cohort of 17 patients were compared with 23 similar surgical patients. There were no differences in baseline characteristics, although lesions were larger in the surgical cohort (7.54 vs 4.37 cm3, P = .017). Despite differences in lesion size, both cohorts had similar extents of ablation/resection (90.7% vs 95.1%, P = .739). Overall survival (14.1 vs 13.8 months, P = .578) and progression-free survival (3.7 vs 3.3 months, P = 0. 495) were similar. LITT patients had significantly shorter hospital stays (2.2 vs 3.0 days, P = .004). Subgroup analysis of patients with lesions ≤20 cm3 showed similar outcomes, with LITT allowing for significantly shorter hospital stays. CONCLUSION: We found no difference in survival outcomes or morbidity between LITT and repeat surgery for surgically accessible rGBM while LITT resulted in shorter hospital stays and more efficient postoperative care.
Electronic medical record-related burnout in healthcare providers: a scoping review of outcomes and interventions

Objective Healthcare provider (HCP) burnout is on the rise with electronic medical record (EMR) use being cited as a factor, particularly with the rise of the COVID-19 pandemic. Burnout in HCPs is associated with negative patient outcomes, and, therefore, it is crucial to understand and address each factor that affects HCP burnout. This study aims to (a) assess the relationship between EMR use and burnout and (b) explore interventions to reduce EMR-related burnout. Methods We searched MEDLINE (Ovid), CINAHL and SCOPUS on 29 July 2021. We selected all studies in English from any publication year and country that discussed burnout in HCPs (physicians, nurse practitioners and registered nurses) related to EMR use. Studies must have reported a quantitative relationship to be included. Studies that implemented an intervention to address this burnout were also included. All titles and abstracts were screened by two reviewers, and all full-text articles were reviewed by two reviewers. Any conflicts were addressed with a third reviewer and resolved through discussion. Quality of evidence of all included articles was assessed using the Quality Rating Scheme for Studies and Other Evidence. Findings The search identified 563 citations with 416 citations remaining after duplicate removal. A review of abstracts led to 59 studies available for full-text assessment, resulting in 25 studies included in the scoping review. Commonly identified associations between EMR-related burnout in HCPs included: message and alert load, time spent on EMRs, organisational support, EMR functionality and usability and general use of EMRs. Two articles employed team-based interventions to improve burnout symptoms without significant improvement in burnout scores. Conclusions and relevance Current literature supports an association between EMR use and provider burnout. Very limited evidence exists for burnout-reducing interventions that address factors such as time spent on EMRs, organisational support or EMR design.
Neurologic complications after cardiopulmonary bypass – A narrative review

Neurologic complications, associated with cardiac surgery and cardiopulmonary bypass (CPB) in adults, are common and can be devastating in some cases. This comprehensive review will not only consider the broad categories of stroke and neurocognitive dysfunction, but it also summarises other neurological complications associated with CPB, and it provides an update about risks, prevention and treatment. Where appropriate, we consider the impact of off-pump techniques upon our understanding of the contribution of CPB to adverse outcomes.
The Assessment of Knowledge of Organisational - Administrative Procedures in the Case of a Bioterrorist Threat in Selected Environmental Populations

Abstract In the past we have seen numerous cases of the purposeful utilisation of micro-organisms and toxins. This situation forced us to undertake actions aimed at a limitation of the production and storage of biological weapons. Unfortunately, despite the signing of the Convention on Biological and Chemical Weapons, many countries are still involved in research into the use of biological agents as a military resource. The objective of the work was to perform an assessment of the knowledge of threats connected with bioterrorism as well as of the procedures in the case of a bioterrorist attack in two different urban populations - i.e. of below 50 thousand and above 500 thousand inhabitants. The study was conducted in two towns, Nysa and Łódź. A self-designed questionnaire included 100 persons from each town, both men and women aged between 18 and 65 years. Despite the small differences between the researched populations, the knowledge of respondents concerning bioterrorist threats and procedures during an attack is insufficient. On the basis of the obtained results we may conclude that there is a need to educate the entire society, irrespective of the place of residence, in order to raise an awareness with regard to the potential threat and procedures in the event of a bioterrorist attack.
Changes in selective attention to articulating mouth across infancy: Sex differences and associations with language outcomes.

Infants' attention to the mouth is thought to support language acquisition, yet this relation has been scantly tested longitudinally. This study assessed attention to the mouth and the eyes at 5.5 (n = 91; Polish, 49% females) and 11 months, between time-point changes and their associations with language development in infancy (11 months) and toddlerhood (24 months). Sex differences were also explored. Results showed an age-related increase in looking to the mouth, and the magnitude of this change was associated with productive language, but only in toddlerhood. By contrast, looking to the eyes did not change and its duration at 5.5 months correlated with language development at 2 years. Exploratory analyses showed that in females but not males, reduced mouth-looking was related to better language outcomes in toddlerhood. Thus, looking to the mouth in infancy likely plays a long-term role in language acquisition and is potentially modulated by participant sex.
A Population-Based Study of Associations Among Child Screen Media Use, Social-Contextual Factors, and School Readiness

This article has supplementary material on the web site: www.jdbp. org. ABSTRACT: Objective: Results of studies examining relations between child media use and school readiness have been inconsistent. Importantly, studies often focus on a single outcome domain (e.g., academic, social, or behavioral), making the comparison of relative importance difficult; fail to account for confounding variables; and fail to investigate social-contextual moderators. This study investigated relations among child media use exposure, social-contextual factors, and multiple domains of school readiness in preschool-aged children. Methods: Multivariate regression analyses were used to examine relations between child media use and 3 domains of school readiness (early learning, social-emotional skills, and self-regulation), controlling for demographic and social-contextual factors, and to investigate differential susceptibility by examining family income and 4 social-contextual factors (sleep, exposure to adverse childhood events, frequency of shared reading, and parent stress) as moderators in a large US population–based sample (N = 9323) of 3 to 5 year olds. Results: After controlling for confounding variables, higher screentime was negatively related to children's social-emotional skills and self-regulation, but less so for early learning. Effect sizes were small. The relation between screentime and self-regulation was significantly moderated by family income, such that the relation was stronger for children from low-income backgrounds. No other evidence of significant moderation was found. Conclusion: Results add to evidence that the relation between screen media use and outcomes in young children is likely complex. Future work should prioritize examining impacts of screen media use on social and behavioral functioning to further inform the evaluation of relative benefits and costs of child screen media use.
Nuclear Potential with Two Pion Exchange

We carefully calculate the nucleon-nucleon interaction due to two pion exchange processes by properly evaluating the corresponding Feynman diagrams. In the estimation, we have made no approximation, and instead, we carry out the numerical integrations of three Feynman parameters. It is found that the two pion exchange potential gives rise to the attractive force which corresponds to the effective scalar meson with its mass of $m_s\simeq 4.7 m_\pi$ and its strength of ${g_s^2\over 4\pi}\simeq 1.45 $. There is a strong isospin dependence of $(\bm{\tau}_1\cdot \bm{\tau}_2)^2 $ which cannot be simulated by the one boson exchange model calculations.
Potential role of bilirubin in preventing retinopathy of prematurity.

BACKGROUND One of the most common problems in preterm neonates is retinopathy of prematurity (ROP). It has been shown antioxidants may be effective in preventing development and progression of ROP. Considering the antioxidant properties of bilirubin, we decided to investigate the bilirubin level in neonates with ROP and compare it with healthy neonates. METHODS This case-control study was performed on VLBW neonates admitted to the NICU of Ghaem Hospital in Mashhad between 2014-2020 years for Jaundice evaluation. Complete neonate's characteristics, maternal history and laboratory results were collected in a questionnaire. Then the neonates were examined for ROP by a fellowship of retina of ophthalmologist at 32 weeks or four weeks after birth. The highest bilirubin levels during their hospitalization were also recorded. RESULTS Of 427 neonates examined, 121 (37.7%) had normal eye examination and 266 (62.3%) had ROP. The mean weight, gestational age and bilirubin were 1455.8± 431.4 gram, 31.6± 2.3 weeks and 8.8 ± 2.4 mg / dl, respectively. There was a significant difference between controls and neonates with ROP with regard to birth weight, duration of intermittent positive pressure ventilation (IPPV), duration of oxygen therapy, first and fifth minute Apgar scores, maximum level of bilirubin and gestational age(P<0.05). It was observed that maximum level of bilirubin was lower in neonates with higher stages of ROP. CONCLUSION According to the results of this study, higher levels of bilirubin in neonates may be a protective factor against ROP, Moreover, increased levels of bilirubin is associated with reduced severity of ROP . Therefore, prophylaxis phototherapy in premature infants may need to be reconsidered.