Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanical Thrombectomy in Nighttime Hours: Is There a Difference in 90-Day Clinical Outcome for Patients with Ischemic Stroke?

BACKGROUND AND PURPOSE: Few data are available regarding the influence of the timing of ischemic stroke management, such as daytime and nighttime hours, on the delay of mechanical thrombectomy, the effectiveness of revascularization, and clinical outcomes. We aimed to investigate whether admission during nighttime hours could impact the clinical outcome (mRS at 90 days) of patients with acute ischemic stroke treated by mechanical thrombectomy. MATERIALS AND METHODS: We retrospectively analyzed 169 patients (112 treated during daytime hours and 57 treated during nighttime hours) with acute ischemic stroke in the anterior cerebral circulation. The main outcome was the rate of patients achieving functional independence at 90 days (mRS ≤2), depending on admission time. RESULTS: In patients admitted during nighttime hours, the rate of mRS ≤ 2 at 90 days was significantly higher (51% versus 35%, P = .05) compared with those admitted in daytime hours. Patients in daytime and nighttime hours were comparable regarding admission and treatment characteristics. However, patients in nighttime hours tended to have a higher median NIHSS score at admission (P = .08) and to be younger (P = .08), especially among the mothership group (P = .09). The multivariate logistic regression analysis confirmed that patients in nighttime hours had better functional outcomes at 90 days than those in daytime hours (P = .018; 95% CI, 0.064–0.770; OR = 0.221). CONCLUSIONS: In a highly organized stroke care network, mechanical thrombectomy is quite effective in the nighttime hours among acute ischemic stroke presentations. Unexpectedly, we found that those patients achieved favorable clinical outcomes more frequently than those treated during daytime hours. Larger series are needed to confirm these results.
Critical Assessment of the Concepts and Misconceptions of the Cardiac Conduction System over the Last 100 Years: The Personal Quest of Robert H. Anderson

Anatomical concepts regarding the conduction system of the heart have been a matter of debate since pioneering work done at the beginning of the 20th century. Robert H. Anderson was actively involved in this field for half a century. We aimed to investigate how his own concepts evolved over time. We have assessed anatomical concepts relating to the cardiac conduction system appearing since the key contributions made in the initial decade of the 20th century, analyzing them from the perspective of Robert H. Anderson, particularly focusing on the anatomical aspects of structures such as accessory atrioventricular pathways, including the so-called Mahaim-type fibers, connections between the atrioventricular node and the atrial myocardium, and so-called “specialized” internodal atrial tracts. To accomplish this task, we have taken as our starting point the initial concepts published in the first decade of the century, along with those subsequently reported up to 1976, and assessing them in the light of our most recently published works. The concepts put forward by Robert Anderson with regard to atrioventricular nodal bypass tracts, atrioventricular nodal inputs, decrementally conducting accessory pathways, and “tracts” for internodal atrial conduction, have remained consistent along the time frame of half a century.
γδT Cells Are Essential for Orthodontic Tooth Movement

Sustained mechanical forces applied to tissue are known to shape local immunity. In the oral mucosa, mechanical stress, either naturally induced by masticatory forces or externally via mechanical loading during orthodontic tooth movement (OTM), is translated, in part, by T cells to alveolar bone resorption. Nevertheless, despite being considered critical for OTM, depletion of CD4+ and CD8+ T cells is reported to have no impact on tooth movement, thus questioning the function of αβT cells in OTM-associated bone resorption. To further address the role of T cells in OTM, we first characterized the leukocytes residing in the periodontal ligament (PDL), the tissue of interest during OTM, and compared it to the neighboring gingiva. Unlike the gingiva, monocytes and neutrophils represent the major leukocytes of the PDL. These myeloid cells were also the main leukocytes in the PDL of germ-free mice, although at lower levels than SPF mice. T lymphocytes were more enriched in the gingiva than the PDL, yet in both tissues, the relative fraction of the γδT cells was higher than the αβ T cells. We thus sought to examine the role of γδT cells in OTM. γδT cells residing in the PDL were mainly Vγ6+ and produced interleukin (IL)–17A but not interferon-γ. Using Tcrd-GDL mice allowing conditional ablation of γδT cells in vivo, we demonstrate that OTM was greatly diminished in the absence of γδT cells. Further analysis revealed that ablation of γδT cells decreased early IL-17A expression, monocyte and neutrophil recruitment, and the expression of the osteoclastogenic molecule receptor activator of nuclear factor–κβ ligand. This, eventually, resulted in reduced numbers of osteoclasts in the pressure site during OTM. Collectively, our data suggest that γδT cells are essential in OTM for translating orthodontic mechanical forces to bone resorption, required for relocating the tooth in the alveolar bone.
ctDNA and Adjuvant Therapy for Colorectal Cancer: Time to Re-Invent Our Treatment Paradigm

Simple Summary There is currently a lack of useful tests to detect microscopic residual disease in patients who have undergone surgery to remove their bowel cancer. This inability to identify patients with microscopic cancer could lead to over- and under-treatment with chemotherapy. Circulating tumour DNA (ctDNA) has shown significant promise to fill this gap to potentially personalize treatment after curative intent surgery allowing de-intensifying and intensifying of adjuvant therapies to reduce unnecessary toxicity of systemic therapy and also to hopefully cure more patients with ‘high risk of relapse’. This review article focuses on the current clinical use and future direction of ctDNA for early-stage bowel cancer. Abstract Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. While there have been significant developments in the treatments for patients with metastatic CRC in recent years, improving outcomes in the adjuvant setting has been more challenging. Recent technological advances in circulating tumour DNA (ctDNA) assay with the ability to detect minimal residual disease (MRD) after curative intent surgery will fundamentally change how we assess recurrence risk and conduct adjuvant trials. Studies in non-metastatic CRC have now demonstrated the prognostic impact of ctDNA analysis after curative intent surgery over and above current standard of care clinicopathological criteria. This ability of ctDNA analysis to stratify patients into low- and very-high-risk groups provides a window of opportunity to personalise adjuvant treatment where escalation/de-escalation of adjuvant systemic therapy could potentially increase cure rates and also reduce treatment-related physical and financial toxicity. Emerging data suggest that conversion of ctDNA from detectable to undetectable after adjuvant chemotherapy may reflect treatment efficacy. This real-time assessment of treatment benefit could be used as a surrogate endpoint for adjuvant novel drug development. Several ctDNA-based randomized adjuvant trials are ongoing internationally to confirm the clinical utility of ctDNA in colorectal cancer.
Caractérisation du fromage Bastelicaccia

Characterization of Bastelicaccia cheese. The cheesemaking parameters and the mi- crobiological, physico-chemical and rheological properties of Bastelicaccia, a soft cheese produced in Corsica, were studied in order to characterize the product. The work was carried out during winter and spring, on 4 farms, two of which transforming goat milk and the two others ewe milk. Bacterial counts revealed that lactococci and leuconostocs (about 8 Log ufc.g -1 ) were dominant in the cheese microflora while enterococci were less numerous (about 5 Log ufc.g -1 ). Cheeses made in winter were significantly different ( p < 0.05) (lower dry matter, lower level of lipolysis, higher level of proteoly- sis, lower firmness) from cheeses made in spring. The variability in cheesemaking conditions, depending on farmhouse producers, resulted in cheeses with significantly different ( p < 0.05) physico-chemical and rheological properties. This characterization of Bastelicaccia cheese provides data basis for physico-chemical, microbial and rheological properties in order to develop quality management of the cheese production in the small-scale traditional units. ewe / goat / milk / cheese
Preference for artificial range enrichment design features in free-range commercial laying hens

ABSTRACT 1. This study examined what elements of artificial enrichment structures attract hens in the outdoor range, and what behaviours hens perform around these structures. Three principles of cover design (height, orientation and visual density) were tested for laying hen preference in the outdoor range of a commercial egg farm using a 2 × 3 × 3 factorial design. The factors were height: 0.5 m or 1.5 m; orientation: vertical, horizontal or horizontal cover with one vertical side; and visual density: 0% (control), 50% or 90% UV blocking cloth. 2. A significant three-way interaction between all factors was found (P < 0.001). The most preferred visual density of these structures was the 90%, followed by 50% UV blocking cloth. Horizontal structures with one vertical side, of either height, were highly preferred. Short horizontal structures were preferred to tall ones, and tall vertical structures were slightly preferred over short ones. 3. The most common behaviours observed around the structures were interaction with the structure (pecks, scratches and vigilance directed at the structure; 32.7%), foraging (32.2%), locomotion (9.9%), and air foraging (pecks and snapping in the air; 9.0%). A three-way interaction between the design principles influenced the proportion of hens performing each of these behaviours (P < 0.001). Hens foraged more around structures with no shade cloth and interacted more with structures that had dense shade cloth. 4. These results highlighted the complexity of designing attractive outdoor environments for laying hens. By testing the combination of elements that hens prefer it is possible to understand how to design attractive outdoor ranges that attract hens and promote a diverse range of behaviours on commercial farms.
TRPM3 Channels Play Roles in Heat Hypersensitivity and Spontaneous Pain after Nerve Injury

Transient receptor potential melastatin 3 (TRPM3) is a heat-activated ion channel in primary sensory neurons of the dorsal root ganglia (DRGs). Pharmacological and genetic studies implicated TRPM3 in various pain modalities, but TRPM3 inhibitors were not validated in TRPM3−/− mice. Here we tested two inhibitors of TRPM3 in male and female wild-type and TRPM3−/− mice in nerve injury-induced neuropathic pain. Transient receptor potential melastatin 3 (TRPM3) is a heat-activated ion channel in primary sensory neurons of the dorsal root ganglia (DRGs). Pharmacological and genetic studies implicated TRPM3 in various pain modalities, but TRPM3 inhibitors were not validated in TRPM3−/− mice. Here we tested two inhibitors of TRPM3 in male and female wild-type and TRPM3−/− mice in nerve injury-induced neuropathic pain. We found that intraperitoneal injection of either isosakuranetin or primidone reduced heat hypersensitivity induced by chronic constriction injury (CCI) of the sciatic nerve in wild-type, but not in TRPM3−/− mice. Primidone was also effective when injected locally in the hindpaw or intrathecally. Consistently, intrathecal injection of the TRPM3 agonist CIM0216 reduced paw withdrawal latency to radiant heat in wild-type, but not in TRPM3−/− mice. Intraperitoneal injection of 2 mg/kg, but not 0.5 mg/kg isosakuranetin, inhibited cold and mechanical hypersensitivity in CCI, both in wild-type and TRPM3−/− mice, indicating a dose-dependent off-target effect. Primidone had no effect on cold sensitivity, and only a marginal effect on mechanical hypersensitivity. Genetic deletion or inhibitors of TRPM3 reduced the increase in the levels of the early genes c-Fos and pERK in the spinal cord and DRGs in CCI mice, suggesting spontaneous activity of the channel. Intraperitoneal isosakuranetin also inhibited spontaneous pain related behavior in CCI in the conditioned place preference assay, and this effect was eliminated in TRPM3−/− mice. Overall, our data indicate a role of TRPM3 in heat hypersensitivity and in spontaneous pain after nerve injury. SIGNIFICANCE STATEMENT Neuropathic pain is a major unsolved medical problem. The heat-activated TRPM3 ion channel is a potential target for novel pain medications, but the pain modalities in which it plays a role are not clear. Here we used a combination of genetic and pharmacological tools to assess the role of this channel in spontaneous pain, heat, cold, and mechanical hypersensitivity in a nerve injury model of neuropathic pain in mice. Our findings indicate a role for TRPM3 in heat hyperalgesia, and spontaneous pain, but not in cold and mechanical hypersensitivity. We also find that not only TRPM3 located in the peripheral nerve termini, but also TRPM3 in the spinal cord or proximal segments of DRG neurons are important for heat hypersensitivity.
CDK4/6 Inhibitor Treatments in Patients with Hormone Receptor Positive, Her2 Negative Advanced Breast Cancer: Potential Molecular Mechanisms, Clinical Implications and Future Perspectives

Simple Summary The recent addition of cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (palbociclib, ribociclib, abemaciclib) to endocrine therapy have remarkably improved the outcome of patients with HR+ advanced breast cancer. However, some points of reflections are still undiscussed. To answer these questions, we revised the mechanism of action of CDK4-6 inhibitors, clinical data available from pivotal studies, and summarized potential future strategies to overcome resistance to CDK4-6 inhibitors, thus improving patient’s survival. Abstract Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer is the most common breast cancer subtype, and endocrine therapy (ET) remains its therapeutic backbone. Although anti-estrogen therapies are usually effective initially, approximately 50% of HR+ patients develop resistance to ET within their lifetime, ultimately leading to disease recurrence and limited clinical benefit. The recent addition of cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (palbociclib, ribociclib, abemaciclib) to ET have remarkably improved the outcome of patients with HR+ advanced breast cancer (ABC) compared with anti-estrogens alone, by targeting the cell-cycle machinery and overcoming some aspects of endocrine resistance. However, which patients are the better candidates for these drugs, which are the main characteristics for a better selection of patients or if there are predictive biomarkers of response, is still unknown. In this review we reported the mechanism of action of CDK4/6 inhibitors as well as their potential mechanism of resistance, their implications in clinical practice and the forthcoming strategies to enhance their efficacy in improving survival and quality of life of patients affected with HR+, HER2−, ABC.
Functional bias of morphine and oliceridine under conditions of minor injury

Recent reports suggest pain from surgical injury may influence the risks associated with exposure to opioids. In mice, hind-paw incision attenuates morphine-primed reinstatement due to kappa opioid receptor activation by dynorphin. In this focused group of studies, we examined the hypotheses that kappa-opioid receptor activation in the nucleus accumbens mediates attenuated drug- primed reinstatement after incisional surgery, and the G-protein biased mu-opioid agonist, oliceridine, leads to less priming of the dynorphin effect in comparison to morphine. To address these hypotheses, adult C57BL/6 male mice underwent intracranial cannulation for administration of the selective kappa-opioid antagonist norBNI directly into the nucleus accumbens. After recovery, they were conditioned with morphine or oliceridine after hind-paw incisional injury, then underwent extinction followed by opioid-primed reinstatement. Intra-accumbal administration of norBNI was carried out prior to testing. The nucleus accumbens and medial prefrontal cortex were extracted and analyzed for expression of prodynorphin. We observed that animals conditioned with morphine in the setting of incisional injury demonstrated blunted responses to opioid-primed reinstatement, and that the blunted responses were reversed with intra-accumbal norBNI administration. Persistently elevated levels of prodynorphin expression in the medial prefrontal cortex and nucleus accumbens were observed in the incised morphine-treated animals. However, both behavioral and molecular changes were absent in animals with incisional injury conditioned with oliceridine. These findings suggest a role for prodynorphin expression in the nucleus accumbens with exposure to morphine after surgery that may protect individuals from relapse not shared with biased mu- opioid receptor agonists.
The Pathogenesis of secondary forms of Autoimmune Inner Ear Disease (AIED): advancing beyond the audiogram data

ABSTRACT Introduction Autoimmune Inner Ear Disease (AIED) can be of a primary or secondary type. To date, a clear pathogenesis of the disease is still not available. Focusing on the secondary forms of AIED, the aim of this review is to (i) assess and describe the hearing involvement in patients affected by autoimmune diseases, (ii) describe the possible association between clinical features (among serological/laboratory data and disease activity/duration) and hearing impairment, (iii) show evidence connecting the AIED types with various etiopathogenetic mechanisms. Areas covered A PRISMA-compliant systematic review was performed. Medline, Cochrane, Embase, and Cinahl were searched from 1 January 2015 through to 5 August 2020. Overall, 16 studies (involving 1043 participants) were included in the review. The data in the literature suggested that bilateral mild-to-moderate sensorineural hearing loss is a commonly reported clinical symptom of AIED. Expert opinion Patients with systemic autoimmune disorders present a cochlear injury which might be associated with the humoral and/or cellular immune response against the inner ear. To date, AIED pathogenesis remains an open issue, due to the rarity of these clinical entities and due to the difficulties in investigating the inner ear immunology, considering the inner ear inaccessibility for tissue sampling.
Cancer, Retrogenes, and Evolution

This review summarizes the knowledge about retrogenes in the context of cancer and evolution. The retroposition, in which the processed mRNA from parental genes undergoes reverse transcription and the resulting cDNA is integrated back into the genome, results in additional copies of existing genes. Despite the initial misconception, retroposition-derived copies can become functional, and due to their role in the molecular evolution of genomes, they have been named the “seeds of evolution”. It is convincing that retrogenes, as important elements involved in the evolution of species, also take part in the evolution of neoplastic tumors at the cell and species levels. The occurrence of specific “resistance mechanisms” to neoplastic transformation in some species has been noted. This phenomenon has been related to additional gene copies, including retrogenes. In addition, the role of retrogenes in the evolution of tumors has been described. Retrogene expression correlates with the occurrence of specific cancer subtypes, their stages, and their response to therapy. Phylogenetic insights into retrogenes show that most cancer-related retrocopies arose in the lineage of primates, and the number of identified cancer-related retrogenes demonstrates that these duplicates are quite important players in human carcinogenesis.
Effect of multiple pregnancy and laterality on infant neurodevelopment

Abstract Objective The objective of this study is to investigate the effect of type of pregnancy (singleton, dizygotic, and monozygotic) on infant neurodevelopment and to explore how laterality operates in this relationship. Methods We constructed a prospective cohort of low-risk women with singleton, monozygotic, and dizygotic pregnancies. Laterality was evaluated using the Edinburgh’s scale of laterality, while neurodevelopment was assessed using the Ages & Stages Questionnaire (ASQ). The confounding, modifying, and mediating effect of laterality on the relationship between multiple pregnancy and neurodevelopment was explored by linear regression. Results We included 207 singletons, 77 dizygotic, and 75 monozygotic pregnancies. The mean age (SD) at assessment of neurodevelopment was 48.5 (7.5) months. There was a significant trend to poorer neurodevelopment across singleton, dizygotic and monozygotic pregnancies in communication (52.2, 47.6 and 42.3; p < .001) and fine movements (49.6, 44.5 and 35.2; p < .001) even after adjusting for confounders. As compared to singletons, both dizygotic (39.6% vs. 22.7%; p < .001) and monozygotic (39.3% vs. 22.7%; p < .001) pregnancies had a higher frequency of non-right laterality. Laterality was not associated with neurodevelopment, nor confounded, mediated or modified the effect of multiple pregnancy on neurodevelopment. Conclusion The association of multiple pregnancy to poorer neurodevelopment was independent of children laterality.
Microstructured Lipid Carriers (MLC) Based on N-Acetylcysteine and Chitosan Preventing Pseudomonas aeruginosa Biofilm

The aim of this work was the development of microstructured lipid carriers (MLC) based on chitosan (CH) and containing N-acetylcysteine (NAC), a mucolytic and antioxidant agent, to inhibit the formation of Pseudomonas aeruginosa biofilm. MLC were prepared using the high shear homogenization technique. The MLC were characterized for morphology, particle size, Z potential, encapsulation efficiency and drug release. The antioxidant properties of NAC-loaded microstructured carriers were evaluated through an in vitro spectrophotometer assay. Finally, the activity of NAC-CH-MLC on biofilm production by Pseudomonas aeruginosa was also evaluated. Results obtained from this study highlighted that the use of chitosan into the inner aqueous phase permitted to obtain microstructured particles with a narrow size range and with good encapsulation efficiency. NAC-loaded MLC showed higher antioxidant activity than the free molecule, demonstrating how encapsulation increases the antioxidant effect of the molecule. Furthermore, the reduction of biofilm growth resulted extremely high with MLC being 64.74% ± 6.2% and 83.74% ± 9.95%, respectively, at 0.5 mg/mL and 2 mg/mL. In conclusion, this work represents a favorable technological strategy against diseases in which bacterial biofilm is relevant, such as cystic fibrosis.