Miracle-dz/UniFAR-FTUs huggingface dataset:
A phase II, single‐center, double‐blind, randomized placebo‐controlled trial to explore the efficacy and safety of intravenous melatonin in surgical patients with severe sepsis admitted to the intensive care unit

To determine whether IV melatonin therapy improves redox status and inflammatory responses in surgical patients with severe sepsis, a unicenter, phase II double‐blind, randomized, placebo‐controlled trial was carried out. The study included patients with severe sepsis marked by infectious systemic inflammatory response syndrome (SIRS), associated with organ dysfunction, hypoperfusion or hypotension requiring surgical intervention. IV melatonin at a daily dose of 60 mg, which was dissolved in 500 ml of 5% dextrose serum, was continuously administered to the patients for over 30 min starting on the day of the diagnoses during a 5‐day period. A total of 14 patients received a placebo treatment and 15 melatonin doses. Redox status decreased in melatonin‐treated patients during the 5 days of treatment as compared to the placebo‐treated patients. Procalcitonin performed better in the melatonin group, whose neutrophil to lymphocyte ratio was also significantly reduced, resulting in an improved evolution of the disease. Moreover, hospital stays decreased by 19.60% from 26.64 days for the placebo group to 21.42 days for the melatonin group. The placebo group recorded five mortalities, as compared to three for the melatonin group. IV melatonin administration improved the course of the disease in surgical patients with severe sepsis, with no side effects. Additional studies with higher doses of melatonin and a long duration of therapy need to be carried out to assess its clinical use.
Melt temperature field measurement in single screw extrusion using thermocouple meshes

The development and validation of a sensor for extrusion melt temperature field measurement is described. A grid of opposing thermocouple wires was constructed and held in position by a supporting frame. Wires were joined together at crossing points to form thermocouple junctions, which were computer monitored. The mesh was used to monitor melt temperature fields during single screw extrusion at the die entrance. Design and construction of the mesh is described in addition to experimental optimization of wire diameter and junction forming. Calibration of the sensor and potential measurement errors including shear heating effects are discussed. Initial results from single screw extrusion are presented for a commercial grade of low density polyethylene using five- and seven-junction thermocouple meshes. The dependence of melt temperature profile on screw speed is illustrated. At low screw speeds melt temperature profiles were flat in shape and higher than set wall temperatures. At higher screw speeds the profiles became more pointed in shape. Use of higher resolution sensors exposed more complex temperature profiles with shoulder regions.
Repurposing of atorvastatin emulsomes as a topical antifungal agent

Abstract Cutaneous fungal infection therapy confronts several issues concerning skin permeation in addition to drug resistance and adverse effects of conventional drugs. The repurposing strategy is supposed to overcome some of those therapeutic obstacles. Recently, atorvastatin (ATO) revealed antifungal activity. ATO is an antihyperlipidemic drug with pH-dependent solubility, which limits skin permeation. This study aims to improve ATO antifungal activity by encapsulation in an emulsomes (EMLs) system, which seeks to ameliorate skin penetration. Therefore, multiple factors were investigated according to the One-Factor-at-a-Time (OFAT) design to achieve the optimum formula with targeted characteristics. Minimizing particle-size and polydispersity-index, besides elevating zeta-potential (ZP) and entrapment-efficiency were the desirable responses during assessing 11 factors. The selected ATO-EMLs formula (E21) recorded 250.5 nm in particle size, polydispersity index of 0.4, ZP of –25.93 mV, and 83.12% of drug entrapped. Morphological study of E21 revealed spherical core–shell vesicles in nanosize. DSC, XRD, and FTIR were conducted to discover the physicochemical properties and confirm emulsomes formation. Optimized ATO-EMLs slowed drug release rate as only 75% of ATO was released after 72 h. Stability study recommended storage between 2 and 8 °C. The in vivo permeation study remarked a homogeneous penetration of EMLs in different skin layers. The in vivo skin irritation test revealed limited histopathological changes. The in vitro and in vivo microbiological studies demonstrated a good antifungal activity of ATO-EMLs. ATO-EMLs system improved antifungal activity as the MIC values reduced from 650 µg/mL for free ATO to 550 µg/mL for ATO-EMLs. These findings may shed light on ATO as an antifungal drug and nanosystems as a tool to support drug repurposing.
Human endogenous retroviruses in cancer: Oncogenesis mechanisms and clinical implications

Human Endogenous Retroviruses (HERVs) are viral sequences integrated into the human genome, resulting from the infection of human germ‐line cells by ancient exogenous retroviruses. Despite losing their replication and retrotransposition abilities, HERVs appear to have been co‐opted in human physiological functions while their aberrant expression is linked to human disease. The role of HERVs in multiple malignancies has been demonstrated, however, the extent to which HERV activation and expression participate in the development of cancer is not yet fully comprehended. In this review article, we discuss the presumed role of HERVs in carcinogenesis and their promising diagnostic and prognostic implications. Additionally, we explore recent data on the HERVs in cancer therapeutics, either through the manipulation of their expression, to induce antitumor innate immunity responses or as cancer immunotherapy targets. Finally, more precise and higher resolution high‐throughput sequencing approaches will further elucidate HERV participation in human physiological and pathological processes.
Strain-induced antipolar phase in hafnia stabilizes robust thin-film ferroelectricity

Hafnia (HfO2) is a promising candidate for next-generation ferroelectric devices due to its robust ferroelectricity at reduced dimensions and its compatibility with silicon technology. Unfortunately, the origin of robust ferroelectricity and the underlying phase transition mechanism in HfO2 remain elusive. Here, we show that its ferroelectricity arises from two phase transitions, where the primary phase transition to antipolar phase is activated by tensile strain. Above a threshold antipolar mode amplitude, a strong cooperative polar-antipolar coupling enables a second ferroelectric phase transition superimposed on the antipolar phase. Because the antipolar mode is not susceptible to depolarization, this polar-antipolar coupling stabilizes the polarization against depolarization effects. Our results demonstrate that tensile strain and polar-antipolar coupling are the origins of ferroelectricity in HfO2 and provide a previously unknown mechanism against depolarization other than conventional improper ferroelectricity.
Ontogenetic shifts in olfactory rosette morphology of the sockeye salmon, Oncorhynchus nerka

Sockeye salmon, Oncorhynchus nerka, are anadromous, semelparous fish that breed in freshwater—typically in streams, and juveniles in most populations feed in lakes for 1 or 2 years, then migrate to sea to feed for 2 or 3 additional years, before returning to their natal sites to spawn and die. This species undergoes important changes in behavior, habitat, and morphology through these multiple life history stages. However, the sensory systems that mediate these migratory patterns are not fully understood, and few studies have explored changes in sensory function and specialization throughout ontogeny. This study investigates changes in the olfactory rosette of sockeye salmon across four different life stages (fry, parr, smolt, and adult). Development of the olfactory rosette was assessed by comparing total rosette size (RS), lamellae number, and lamellae complexity from scanning electron microscopy images across life stages, as a proxy for olfactory capacity. Olfactory RS increased linearly with lamellae number and body size (p < .001). The complexity of the rosette, including the distribution of sensory and nonsensory epithelia and the appearance of secondary lamellar folding, varied between fry and adult life stages. These differences in epithelial structure may indicate variation in odor‐processing capacity between juveniles imprinting on their natal stream and adults using those odor memories in the final stages of homing to natal breeding sites. These findings improve our understanding of the development of the olfactory system throughout life in this species, highlighting that ontogenetic shifts in behavior and habitat may coincide with shifts in nervous system development.
Gender differences in interactions and depressive symptoms among hospitalized older patients living with dementia

Abstract Alzheimer’s disease or a related dementia (ADRD) disproportionately affects women with two-thirds of individuals with ADRD comprised of women. This study examined gender-related differences in the quality of staff-patient interactions and depressive symptoms among hospitalized older patients living with dementia. This secondary analysis utilized baseline data of 140 hospitalized older patients with dementia who participated in the final cohort of a randomized controlled trial (ClinicalTrials.gov identifier: NCT03046121) implementing Family centered Function-focused Care (Fam-FFC). On average, the participants (male = 46.1%, female = 52.9%) were 81.43 years old (SD = 8.29), had positive interactions with staff and lower depressive symptoms based on Quality of Interaction Schedule (QUIS) scores and Cornell Scale for Depression in Dementia (CSDD) scores, respectively. Although males had more positive interactions (male = 6.06, SD = 1.13; female = 5.59, SD = 1.51) and lesser depressive symptoms (male = 7.52, SD = 4.77; female = 8.03, SD = 6.25) than females, no statistically significant gender differences were observed in linear models with appropriate covariates or multivariant analysis of covariant (MANCOVA). However, the multigroup regression conducted to further probe marginally significant moderation effect of gender and pain on staff-patient interactions demonstrated that greater pain was significantly related to lower quality or less positive staff-patient interactions for females compared to males (χ 2 diff (1) = 4.84, p = . 03). Continued evaluation of gender differences is warranted to inform care delivery and interventions to improve care for hospitalized older patients with dementia.
Model‐Free and Model‐based Parameters Derived From CAIPIRINHA‐Dixon‐TWIST‐VIBE DCE‐MRI: Associations With Prognostic Factors and Molecular Subtypes of Invasive Ductal Breast Cancer

CAIPIRINHA‐Dixon‐TWIST‐VIBE (CDTV) dynamic contrast‐enhanced MRI (DCE‐MRI) can be used to characterize breast cancer. However, the influence of the clinicopathologic factors and molecular subtypes of invasive breast carcinoma (IDC) on the model‐free and model‐based parameters has not been investigated.
Micromachined Piezoelectric Microspeaker

A diaphragm-based piezoelectric microspeaker is fabricated on a heavily compressive silicon–nitride film, and is compared to commercial speakers. The largest sound pressure level (SPL) produced by the fabricated microspeaker is 92 dB (when measured 2 mm away from the microspeaker in open field) at around 3 kHz for 6 Vpeak-to-peak input. The microspeaker produces a comparable sound output as a commercial piezo-ceramic and electro-dynamic speaker used in current cellular phones. The keys to this success are as follows: (1) the usage of a diaphragm that has a very high compressive residual stress, high enough to cause the diaphragm to be wrinkled and (2) the usage of high quality ZnO film deposited by two-step deposition technique.
Instability of ferrofluid magnetic drops under magnetic field

Résumé. Abstract. 2014 We have followed the evolution of the shape of ferrofluid magnetic drops in presence of a magnetic field. The prolate ellipsoid shape of the drop becomes unstable for a certain magnetic field threshold : the drop jumps from a slightly elongated shape to a much more elongated shape. When decreasing the magnetic field the same feature occurs for a smaller threshold. This instability is simply understood from a balance between magnetic energy and interfacial tension energy.
Therapeutic approaches for the management of higher risk myelodysplastic syndromes

Abstract The heterogeneous nature of myelodysplastic syndromes (MDS) demands a risk-adapted therapeutic approach, and higher risk MDS, characterized by an increased risk of transformation into acute myeloid leukemia and inferior survival, is typically defined based on an integrated assessment of cytopenias, bone marrow blast percentage, and cytogenetic findings using the revised International Prognostic Scoring System. Incorporating mutational data could further refine the risk assessment and identify those with higher-than-expected disease risk. The principal therapeutic goal in this disease subset is to modify the natural history and prolong survival. Allogeneic stem cell transplant, the only potentially curative treatment, should be offered to eligible patients. Hypomethylating agents are the only approved treatment with unsatisfactory response rates and duration, and patients who failed prior hypomethylating agents unfortunately have dismal outcomes with urgent need of novel therapeutic agents. In this review, we provide the therapeutic landscape in higher risk MDS based on the current evidence and discuss the investigational treatment options under development.
On upper bounds of Manin type

We introduce a certain birational invariant of a polarized algebraic variety and use that to obtain upper bounds for the counting functions of rational points on algebraic varieties. Using our theorem, we obtain new upper bounds of Manin type for 28 deformation types of smooth Fano $3$-folds of Picard rank $\geq 2$ following Mori-Mukai's classification. We also find new upper bounds for polarized K3 surfaces $S$ of Picard rank $1$ using Bayer-Macri's result on the nef cone of the Hilbert scheme of two points on $S$.
Statistical modeling of hormesis quantities in inverted U-shaped dose-response relationships by reparameterization of a bilogistic model

Abstract Statistical procedures that allow quantitative determination of hormesis features are required for quantitative characterization of hormesis to provide information on the biphasic dose-response phenomenon and its variability. Only a direct estimate of individual effective doses in hormetic dose-response relationships is possible using prior extensions of the bilogistic model of Beckon and coworkers. This study presented further extensions of the model to determine the toxic potency and hormetic dose zone by estimating two effective doses simultaneously. In addition, the extended models allow for partitioning the hormetic dose zone through the dose of maximum stimulation. This study demonstrated a 4-step statistical modeling approach to quantify 20 hormesis quantities. The applicability and challenges of the mathematical procedures are discussed based on a few examples of hormetic dose-response relationships. The syntaxes for the analyses were provided as Appendix to demonstrate its implementation in SAS® statistical software. Given the variability of hormetic dose-responses generated from toxicological studies in many disciplines, the proposed approach cannot apply to all dose-response patterns. However, we hope the proposed extensions could provide versatile statistical tools for quantitatively exploring a variety of biphasic dose-response curves.
Age-related changes in fast spindle clustering during NREM sleep and their relevance for memory consolidation.

Sleep plays a crucial role in memory consolidation. Recent data in rodents and young adults revealed that fast spindle band power fluctuates at a 0.02-Hz infraslow scale during non-rapid eye movement (NREM) sleep. These fluctuations result from a periodic temporal clustering of spindles and may modulate sleep maintenance and memory consolidation. With age, sleep undergoes substantial changes but age-related changes in spindle clustering have never been investigated. Polysomnography data were collected in 147 older (mean age ± SD: 69.3 ± 4.1 years) and 32 young-middle aged (34.5 ± 10.9 years) adults. Sleep-dependent memory consolidation was assessed in a subsample of 57 older adults using a visuospatial memory task. We analyzed power fluctuations in fast spindle frequency band, detected fast spindles and quantified their clustering during the night separating encoding and retrieval. Fast spindle band power fluctuated at a 0.02-Hz infraslow scale in young-middle aged and older adults. However, the proportion of clustered fast spindles decreased non-linearly with age (p < 0.001). This effect was not mediated by NREM sleep fragmentation. The clustering level of fast spindles modulated their characteristics (p < 0.001). Finally, the mean size of spindle clusters was positively associated with memory consolidation (p = 0.036) and negatively with NREM sleep micro-arousals density (p = 0.033). These results suggest that clusters of fast spindles may constitute stable sleep periods promoting off-line processes such as memory consolidation. We emphasize the relevance of considering spindle dynamics, obviously impaired during ageing, to understand the impact of age-related sleep changes on memory.
Ferulic acid alleviates alveolar epithelial barrier dysfunction in sepsis-induced acute lung injury by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis

Abstract Context Ferulic acid (FA) has antioxidative and anti-inflammatory effects, and is a promising drug to treat sepsis. Objective To study the therapeutic effect of FA in sepsis-induced acute lung injury (ALI) and its underlying mechanisms. Materials and methods The caecal ligation and puncture (CLP) manoeuvre was applied to establish a murine model of sepsis-induced ALI, and female BALB/c mice (6 mice per group) were subjected to 100 mg/kg FA or 0.8 mg/kg ferrostatin-1 (Fer-1, ferroptosis inhibitor) treatment to clarify the role of FA in preserving alveolar epithelial barrier function and inhibiting ferroptosis. Lipopolysaccharide (LPS; 500 ng/mL)-induced cell models were prepared and subjected to FA (0.1 μM), sh-Nrf2, and Fe (Fe-citrate, ferroptosis inducer; 5 M) treatment to study the in vitro effect of FA on LPS-induced alveolar epithelial cell injury and the role of the Nrf2/HO-1 pathway. Results We found that FA decreased the lung injury score (48% reduction), lung wet/dry weight ratio (33% reduction), and myeloperoxidase activity (58% reduction) in sepsis-induced ALI. Moreover, FA inhibited ferroptosis of alveolar epithelial cells and improved alveolar epithelial barrier dysfunction. The protective role of FA against alveolar epithelial barrier dysfunction could be reversed by the ferroptosis inducer Fe-citrate, suggesting that FA alleviates alveolar epithelial barrier dysfunction by inhibiting ferroptosis. Mechanistically, we found that FA inhibited ferroptosis of alveolar epithelial cells by activating the Nrf2/HO-1 pathway. Conclusion Collectively, our data highlighted the alleviatory role of ferulic acid in sepsis-induced ALI by activating the Nrf2/HO-1 pathway and inhibiting ferroptosis, offering a new basis for sepsis treatment.
A SHORT NOTE ON SECOND‐ORDER STOCHASTIC DOMINANCE PRESERVING COHERENT RISK MEASURES

We improve results on law invariant coherent risk measures satisfying the Fatou property due to Kusuoka (2001; Adv. Math. Econ. 3, 83–95) by considering risk measures which are in addition second order stochastic dominance preserving. In particular, we derive a representation result for such risk measures.
Control of Gαq signaling dynamics and GPCR cross-talk by GRKs

Numerous processes contribute to the regulation of G protein–coupled receptors (GPCRs), but relatively little is known about rapid mechanisms that control signaling on the seconds time scale or regulate cross-talk between receptors. Here, we reveal that the ability of some GPCR kinases (GRKs) to bind Gαq both drives acute signaling desensitization and regulates functional interactions between GPCRs. GRK2/3-mediated acute desensitization occurs within seconds, is rapidly reversible, and can occur upon local, subcellular activation. This rapid desensitization is kinase independent, insensitive to pharmacological inhibition, and generalizable across receptor families and effectors. We also find that the ability of GRK2 to bind G proteins also enables it to regulate the extent and timing of Gαq-dependent signaling cross-talk between GPCRs. Last, we find that G protein/GRK2 interactions enable a novel form of GPCR trafficking cross-talk. Together, this work reveals potent forms of Gαq-dependent GPCR regulation with wide-ranging pharmacological and physiological implications.
Early and long-term prognosis in patients with remaining chronic total occlusions after revascularization attempt. A cohort study from the SKEJ-CTO registry

Abstract Objectives The present study aimed to compare safety and long-term prognosis of patients with chronic total coronary occlusions (CTO) stratified for remaining CTOs after percutaneous coronary intervention (PCI). Design The study cohort consisted of patients with coronary artery disease who underwent CTO PCI in a high volume tertiary center from 2009 to 2019 and were registered in Danish high-quality registers. Patients with successful PCI of all CTOs were compared to patients with ≥1 remaining CTO post-procedural. Primary endpoints were analysed using Cox-regression and Kaplan-Meier estimates, and included all-cause mortality, major adverse cardio- and cerebrovascular events (MACCE) and a 30-day safety endpoint. Results Procedural success rate was 87.7%, and 76.5% of patients had all CTO(s) opened post-PCI. Safety endpoint occurred in 4.6% of patients, and more frequently in patients with remaining CTO(s) (RD 4.9, 95%CI 0.1, 9.8). All-cause mortality was higher in patients with remaining CTO(s) (Unadjusted HR 1.65, 95% CI 1.03, 2.47, p = .015. Adjusted HR 1.32, 95%CI 0.88–1.99, p = .18) after eight years of follow-up. Risk of MACCE was significantly higher in patients with remaining CTO(s) (Unadjusted HR 1.79, 95% CI 1.34–2.41, p < .001. Adjusted HR 1.51, 95% CI 1.11–2.05, p = .009). Conclusions In our centre, CTO PCI was associated with high success rate and low risk of 30-days complications. Presence of remaining CTO(s) after final revascularization attempt was associated with higher but statistically insignificant long-term mortality but was an independent predictor of MACCE.
Comment on “The Use of Invalid Polar Cap South (PCS) Indices in Publications” by Stauning

Declaration (Stauning, 2022, https://doi.org/10.1029/2022JA030355) on “invalid polar cap south (PCS) index” is based on the following arguments: PCS index is calculated with use of incorrect “unified” PC derivation method; PCS index used in analyses is a preliminary index, which was not approved by IAGA and, therefore, it cannot be regarded as a correct index; PCN and PCS indices demonstrate, intermittently, large difference in value, which should be treated as evidence of the PCS index invalidity. The paper presents comments to these arguments. Conclusion is made that criticism of the PCS index, presented in Stauning (2022, https://doi.org/10.1029/2022JA030355), is based on groundless arguments.