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We report on tunneling spectroscopy measurements using a scanning tunneling microscope (STM) on the spin triplet superconductor Sr2RuO4. A fully open gap, close to the Bardeen-Cooper-Schrieffer (BCS) value, is found, which disappears at the bulk Tc = 1.5 K. The results are discussed in the framework of recent multigap scenarios for an unconventional spin triplet superconductor. [ABSTRACT FROM AUTHOR]

Background: Palliative care focuses on the prevention of worsening health, improving the quality of the patient's life, and the relief of suffering, and therefore has a considerable impact on both the patient suffering from a life-threatening or potentially life-threatening illness and on their family. Spirituality, as the dimension of human life involving the search for meaning, purpose, and transcendence, and connection with oneself, others, and the sacred, could be essential in supporting these patients. The aim of this study was to synthesise the scientific evidence describing the interventions and/or activities undertaken to meet the spiritual needs of the palliative patient., Methods: A literature search was carried out across the following databases: PubMed, LILACS, Scopus, and Web of Science. The PRISMA statement was used to guide this review., Results: Twenty-four articles were included. The thematic categories included spiritual needs at the end of life, the influence of music and dance as palliative care, care for family caregivers, and the comparison between counselling and dignity therapy., Conclusions: Interventions in the biopsychosocial-spiritual spheres impact on the patient's peace of mind and promote the acceptance of a "good death". Healthcare personnel play an essential role in the way their patients prepare for the moment of death, and the meaning and values they convey help them to accompany and welcome patients. Last but not least, universities can play a crucial role by training nurses to integrate spiritual interventions such as music and dance, or by considering the family as a unit of care. The systematic review protocol was registered in the Prospective International Register of Systematic Reviews (PROSPERO) under protocol number CRD42023490852.

Advances in artificial intelligence (AI) raise important questions about whether people view moral evaluations by AI systems similarly to human-generated moral evaluations. We conducted a modified Moral Turing Test (m-MTT), inspired by Allen et al. (Exp Theor Artif Intell 352:24-28, 2004) proposal, by asking people to distinguish real human moral evaluations from those made by a popular advanced AI language model: GPT-4. A representative sample of 299 U.S. adults first rated the quality of moral evaluations when blinded to their source. Remarkably, they rated the AI's moral reasoning as superior in quality to humans' along almost all dimensions, including virtuousness, intelligence, and trustworthiness, consistent with passing what Allen and colleagues call the comparative MTT. Next, when tasked with identifying the source of each evaluation (human or computer), people performed significantly above chance levels. Although the AI did not pass this test, this was not because of its inferior moral reasoning but, potentially, its perceived superiority, among other possible explanations. The emergence of language models capable of producing moral responses perceived as superior in quality to humans' raises concerns that people may uncritically accept potentially harmful moral guidance from AI. This possibility highlights the need for safeguards around generative language models in matters of morality., (© 2024. The Author(s).)

Immunometabolic reprogramming due to adenosine produced by CD73 (encoded by the 5'-ectonucleotidase gene NT5E ) is a recognized immunosuppressive mechanism contributing to immune evasion in solid tumors. Adenosine is not only known to contribute to tumor progression, but it has specific roles in driving dysfunction of immune cells, including natural killer (NK) cells. Here, we engineered human NK cells to directly target the CD73-adenosine axis by blocking the enzymatic activity of CD73. In doing so, the engineered NK cells not only impaired adenosinergic metabolism driven by the hypoxic uptake of ATP by cancer cells in a model of non-small-cell lung cancer, but also mediated killing of tumor cells due to the specific recognition of overexpressed CD73. This resulted in a 'single agent' immunotherapy that combines antibody specificity, blockade of purinergic signaling, and killing of targets mediated by NK cells. We also showed that CD73-targeted NK cells are potent in vivo and result in tumor arrest, while promoting NK cell infiltration into CD73 + tumors and enhancing intratumoral activation., Competing Interests: AC, KL, JW, JC, SU, NL, VB, SJ, SP, ST, BE, SM No competing interests declared, (© 2022, Chambers et al.)

Tumor antigen heterogeneity, a severely immunosuppressive tumor microenvironment (TME) and lymphopenia resulting in inadequate immune intratumoral trafficking, have rendered glioblastoma (GBM) highly resistant to therapy. To address these obstacles, here we describe a unique, sophisticated combinatorial platform for GBM: a cooperative multifunctional immunotherapy based on genetically engineered human natural killer (NK) cells bearing multiple antitumor functions including local tumor responsiveness that addresses key drivers of GBM resistance to therapy: antigen escape, immunometabolic reprogramming of immune responses, and poor immune cell homing. We engineered dual-specific chimeric antigen receptor (CAR) NK cells to bear a third functional moiety that is activated in the GBM TME and addresses immunometabolic suppression of NK cell function: a tumor-specific, locally released antibody fragment which can inhibit the activity of CD73 independently of CAR signaling and decrease the local concentration of adenosine. The multifunctional human NK cells targeted patient-derived GBM xenografts, demonstrated local tumor site-specific activity in the tissue, and potently suppressed adenosine production. We also unveil a complex reorganization of the immunological profile of GBM induced by inhibiting autophagy. Pharmacologic impairment of the autophagic process not only sensitized GBM to antigenic targeting by NK cells but promoted a chemotactic profile favorable to NK infiltration. Taken together, our study demonstrates a promising NK cell-based combinatorial strategy that can target multiple clinically recognized mechanisms of GBM progression simultaneously., Competing Interests: The authors declare no competing interest.

Objective: The histopathologic wear patterns in glenohumeral osteoarthritis (GOA) have not been described. The aims of the study were to a) describe the histopathology of humeral head wear patterns in patients with end-stage GOA and b) identify clinical and radiographic parameters that correlate with observed histopathological wear patterns., Methods: Eighteen humeral heads from patients undergoing anatomic total shoulder arthroplasty for end-stage osteoarthritis were divided radially into eight wedge-shaped zones. Each zone was subdivided into central and peripheral regions. Histologic analysis included measurements of cartilage and subchondral bone plate thickness, subchondral bone area, and cartilage structure was scored using the Osteoarthritis Research Society (OARSI) and modified Mankin systems. Clinical variables including patient history, physical exam, functional evaluation, and radiographic assessments were evaluated for correlations with humeral head characteristics., Results: Overall, humeral heads demonstrated a pattern of central and inferior cartilage damage, loss, and subchondral bone changes. However, within the group, composite maps of individual patient wear patterns demonstrated a sub-group of patients with a more focal inferior cartilage lesion. Overall, these more focal inferior lesions were associated with greater pre-operative range of motion (in both upper extremities), higher pre-operative SANE and ASES scores, female sex, non-dominant extremity, concentric wear patterns, and smaller inferior osteophytes., Conclusion: Humeral head cartilage wear patterns in GOA include central and inferior cartilage damage and loss. A histopathological distinction was identified between patients with more focal versus diffuse wear, which may manifest clinically with preservation of function and range of motion, and with less profound radiographical changes., Competing Interests: No author had competing interests or conflicts of interest., (© 2021 The Authors.)

The Hessian fly is an obligate parasite of wheat causing significant economic damage, and triggers either a resistant or susceptible reaction. However, the molecular mechanisms of susceptibility leading to the establishment of the larvae are unknown. Larval survival on the plant requires the establishment of a steady source of readily available nutrition. Unlike other insect pests, the Hessian fly larvae have minute mandibles and cannot derive their nutrition by chewing tissue or sucking phloem sap. Here, we show that the virulent larvae produce the glycoside hydrolase MdesGH32 extra-orally, that localizes within the leaf tissue being fed upon. MdesGH32 has strong inulinase and invertase activity aiding in the breakdown of the plant cell wall inulin polymer into monomers and converting sucrose, the primary transport sugar in plants, to glucose and fructose, resulting in the formation of a nutrient-rich tissue. Our finding elucidates the molecular mechanism of nutrient sink formation and establishment of susceptibility.

Probiotic bacteria reduce the intestinal colonization of pathogens. Yet, their use in preventing fatal infection caused by foodborne Listeria monocytogenes (Lm), is inconsistent. Here, we bioengineered Lactobacillus probiotics (BLP) to express the Listeria adhesion protein (LAP) from a non-pathogenic Listeria (L. innocua) and a pathogenic Listeria (Lm) on the surface of Lactobacillus casei. The BLP strains colonize the intestine, reduce Lm mucosal colonization and systemic dissemination, and protect mice from lethal infection. The BLP competitively excludes Lm by occupying the surface presented LAP receptor, heat shock protein 60 and ameliorates the Lm-induced intestinal barrier dysfunction by blocking the nuclear factor-κB and myosin light chain kinase-mediated redistribution of the major epithelial junctional proteins. Additionally, the BLP increases intestinal immunomodulatory functions by recruiting FOXP3 + T cells, CD11c + dendritic cells and natural killer cells. Engineering a probiotic strain with an adhesion protein from a non-pathogenic bacterium provides a new paradigm to exclude pathogens and amplify their inherent health benefits.

Volumetric muscle loss (VML) injuries characterized by critical loss of skeletal muscle tissues result in severe functional impairment. Current treatments involving use of muscle grafts are limited by tissue availability and donor site morbidity. In this study, we designed and synthesized an implantable glycosaminoglycan-based hydrogel system consisting of thiolated hyaluronic acid (HA) and thiolated chondroitin sulfate (CS) cross-linked with poly(ethylene glycol) diacrylate to promote skeletal muscle regeneration of VML injuries in mice. The HA-CS hydrogels were optimized with suitable biophysical properties by fine-tuning degree of thiol group substitution to support C2C12 myoblast proliferation, myogenic differentiation and expression of myogenic markers MyoD, MyoG and MYH8. Furthermore, in vivo studies using a murine quadriceps VML model demonstrated that the HA-CS hydrogels supported integration of implants with the surrounding host tissue and facilitated migration of Pax7 + satellite cells, de novo myofiber formation, angiogenesis, and innervation with minimized scar tissue formation during 4-week implantation. The hydrogel-treated and autograft-treated mice showed similar functional improvements in treadmill performance as early as 1-week post-implantation compared to the untreated groups. Taken together, our results demonstrate the promise of HA-CS hydrogels as regenerative engineering matrices to accelerate healing of skeletal muscle injuries., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.D., N.N, S.K. and L.K. have applied for patents related to this study. M.D. is founder of Adipo Therapeutics, LLC., (© 2020 [The Author/The Authors].)

Unlabelled: The intra-abdominal umbilical vein varix is very uncommon, characterized by a dilation of the vein, usually located between its entry into the abdomen and completion in the portal system. However, the location of this anomaly to extra-abdominal level is very unusual and more difficult to diagnose by ultrasound., Clinical Case: We present a case undiagnosed during pregnancy, demonstrating cord abnormality in its extra-abdominal portion and confirmed later by the pathology study. It was a gestation of 36 + 6 weeks, ending by performing emergency caesarean section for abnormal fetal heart rate, with good perinatal outcome. The diagnosis was made after placental delivery, by the existence of fibrotic cystic structure in the middle third of the umbilical cord.

Neurofibromatosis 1 (NF1) is a genetic condition generally associated with intellectual deficiency and learning disabilities. Although there have been groundbreaking advances in the understanding of the molecular, cellular, and neural systems underlying learning deficits associated to NF1 in animal models, much remains to be learned about the spectrum of neurocognitive phenotype associated with the NF1 clinical syndrome. In the present study, 32 children with NF1 ranging from 7 to 14 years were evaluated with neurocognitive tests dedicated to assess basic capacities which are involved in reading and mathematical achievement. Deficits in lexical and phonological strategies and poor number facts retrieval were found underlying reading and arithmetic disorders, respectively. Additionally, efficiencies in lexical/phonological strategies and mental arithmetic were significant predictors of individual differences in reading attainment and math. However, deficits in core numeric capacities were not found in the sample, suggesting that it is not responsible for calculation dysfluency. The estimated prevalence of Developmental Dyscalculia was 18.8%, and the male:female ratio was 5:1. On the other hand, the prevalence of Developmental Dyslexia was almost 3 times as high (50%), and no gender differences were found (male: female ratio = 1:1). This study offers new evidence to the neurocognitive phenotype of NF1 contributing to an in depth understanding of this condition, but also to possible treatments for the cognitive deficits associated with NF1.

The first aim of the present study was to investigate whether numerical effects (Numerical Distance Effect, Counting Effect and Subitizing Effect) are domain-specific predictors of mathematics development at the end of elementary school by exploring whether they explain additional variance of later mathematics fluency after controlling for the effects of general cognitive skills, focused on nonnumerical aspects. The second aim was to address the same issues but applied to achievement in mathematics curriculum that requires solutions to fluency in calculation. These analyses assess whether the relationship found for fluency are generalized to mathematics content beyond fluency in calculation. As a third aim, the domain specificity of the numerical effects was examined by analyzing whether they contribute to the development of reading skills, such as decoding fluency and reading comprehension, after controlling for general cognitive skills and phonological processing. Basic numerical capacities were evaluated in children of 3(rd) and 4(th) grades (n=49). Mathematics and reading achievements were assessed in these children one year later. Results showed that the size of the Subitizing Effect was a significant domain-specific predictor of fluency in calculation and also in curricular mathematics achievement, but not in reading skills, assessed at the end of elementary school. Furthermore, the size of the Counting Effect also predicted fluency in calculation, although this association only approached significance. These findings contrast with proposals that the core numerical competencies measured by enumeration will bear little relationship to mathematics achievement. We conclude that basic numerical capacities constitute domain-specific predictors and that they are not exclusively "start-up" tools for the acquisition of Mathematics; but they continue modulating this learning at the end of elementary school.