Compass-like manipulation of electronic nematicity in Sr3Ru2O7.

Electronic nematicity has been found in a wide range of strongly correlated electron materials, resulting in the electronic states having-4.5pc]Please note that the spelling of the following author name(s) in the manuscript differs from the spelling provided in the article metadata: Izidor Benedicic. The spelling provided in the manuscript has been retained; please confirm. a symmetry that is lower than that of the crystal that hosts them. One of the most astonishing examples is [Formula: see text], in which a small in-plane component of a magnetic field induces significant resistivity anisotropy. The direction of this anisotropy follows the direction of the in-plane field. The microscopic origin of this field-induced nematicity has been a long-standing puzzle, with recent experiments suggesting a field-induced spin density wave driving the anisotropy. Here, we report spectroscopic imaging of a field-controlled anisotropy of the electronic structure at the surface of [Formula: see text]. We track the electronic structure as a function of the direction of the field, revealing a continuous change with the angle. This continuous evolution suggests a mechanism based on spin-orbit coupling resulting in compass-like control of the electronic bands. The anisotropy of the electronic structure persists to temperatures about an order of magnitude higher compared to the bulk, demonstrating novel routes to stabilize such phases over a wider temperature range.

Intensive salvage chemotherapy with VDTPACE or mCBAD followed by hematopoietic stem-cell support for refractory/relapsed multiple myeloma.

INTRODUCTION: Triple- and quad-refractory multiple myeloma patients usually have an aggressive course and a poor prognosis. Available therapeutic options are scarce. METHODS: The objective of the current study was to evaluate responses and toxicities of VDTPACE or mCBAD with hematopoietic stem-cell support as a bridge to subsequent therapies in patients with refractory/relapsed multiple myeloma. RESULTS: Thirteen patients were included (11 mCBAD, 2 VDTPACE), and 21 cycles of chemotherapy with hematopoietic stem-cell support were delivered. Mean number of previous therapies was 4.8. Stem cells were infused on a median day 9.9 after chemotherapy. Mean time to neutrophil recovery was 18.2 days in patients receiving the first cycle and 15.9 following subsequent cycles. Before therapy, most patients were in PD (77%), PR (15%), or VGPR (8%). Following treatment, the best responses achieved were PR (46%), VGPR (46%), and CR (8%). Median overall and progression-free survivals were 17 and 9 months. There has been no case of non-relapse mortality. In the 21 cycles, the main complications were infectious. CONCLUSION: Intensive chemotherapy can decrease disease burden in patients with relapsed/refractory MM, and stem-cell support can successfully decrease toxicities and treatment-related mortality associated with these regimens and may be a good bridging option.

Validity and reliability evidence support task-specific metrics for laparoscopic fundoplication.

BACKGROUND: Laparoscopic hiatal hernia repair (LHHR) is a complex operation requiring advanced surgical training. Surgical simulation offers a potential solution for learning complex operations without the need for high surgical volume. Our goal is to develop a virtual reality (VR) simulator for LHHR; however, data supporting task-specific metrics for this procedure are lacking. The purpose of this study was to develop and assess validity and reliability evidence of task-specific metrics for the fundoplication phase of LHHR. METHODS: In phase I, structured interviews with expert foregut surgeons were conducted to develop task-specific metrics (TSM). In phase II, participants with varying levels of surgical expertise performed a laparoscopic Nissen fundoplication procedure on a porcine stomach explant. Video recordings were independently assessed by two blinded graders using global and TSM. An intraclass correlation coefficient (ICC) was used to assess interrater reliability (IRR). Performance scores were compared using a Kruskal-Wallis test. Spearman's rank correlation was used to evaluate the association between global and TSM. RESULTS: Phase I of the study consisted of 12 interviews with expert foregut surgeons. Phase II engaged 31 surgery residents, a fellow, and 6 attendings in the simulation. Phase II results showed high IRR for both global (ICC = 0.84, p < 0.001) and TSM (ICC = 0.75, p < 0.001). Significant between-group differences were detected for both global (χ2 = 24.01, p < 0.001) and TSM (χ2 = 18.4, p < 0.001). Post hoc analysis showed significant differences in performance between the three groups for both metrics (p < 0.05). There was a strong positive correlation between the global and TSM (rs = 0.86, p < 0.001). CONCLUSION: We developed task-specific metrics for LHHR and using a fundoplication model, we documented significant reliability and validity evidence. We anticipate that these LHHR task-specific metrics will be useful in our planned VR simulator.

Automated segmentation of phases, steps, and tasks in laparoscopic cholecystectomy using deep learning.

BACKGROUND: Video-based review is paramount for operative performance assessment but can be laborious when performed manually. Hierarchical Task Analysis (HTA) is a well-known method that divides any procedure into phases, steps, and tasks. HTA requires large datasets of videos with consistent definitions at each level. Our aim was to develop an AI model for automated segmentation of phases, steps, and tasks for laparoscopic cholecystectomy videos using a standardized HTA. METHODS: A total of 160 laparoscopic cholecystectomy videos were collected from a publicly available dataset known as cholec80 and from our own institution. All videos were annotated for the beginning and ending of a predefined set of phases, steps, and tasks. Deep learning models were then separately developed and trained for the three levels using a 3D Convolutional Neural Network architecture. RESULTS: Four phases, eight steps, and nineteen tasks were defined through expert consensus. The training set for our deep learning models contained 100 videos with an additional 20 videos for hyperparameter optimization and tuning. The remaining 40 videos were used for testing the performance. The overall accuracy for phases, steps, and tasks were 0.90, 0.81, and 0.65 with the average F1 score of 0.86, 0.76 and 0.48 respectively. Control of bleeding and bile spillage tasks were most variable in definition, operative management, and clinical relevance. CONCLUSION: The use of hierarchical task analysis for surgical video analysis has numerous applications in AI-based automated systems. Our results show that our tiered method of task analysis can successfully be used to train a DL model.

Narwhal (Monodon monoceros) echolocation click rates to support cue counting passive acoustic density estimation.

Estimating animal abundance is fundamental for effective management and conservation. It is increasingly done by combining passive acoustics with knowledge about rates at which animals produce cues (cue rates). Narwhals (Monodon monoceros) are elusive marine mammals for which passive acoustic density estimation might be plausible, but for which cue rates are lacking. Clicking rates in narwhals were investigated using a dataset from sound and movement tag records collected in August 2013-2016 and 2019 in East Greenland. Clicking rates were quantified for ∼1200 one-second-long systematic random samples from 8 different whales. Generalized additive models were used to model (1) the probability of being in a clicking state versus depth and (2) the clicking rate while in a clicking state, versus time and depth. The probability of being in a clicking state increased with depth, reaching ∼1.0 at ∼500 m, while the number of clicks per second (while in a clicking state) increased with depth. The mean cue production rate, weighted by tag duration, was 1.28 clicks per second (se = 0.13, CV = 0.10). This first cue rate for narwhals may be used for cue counting density estimation, but care should be taken if applying it to other geographical areas or seasons, given sample size, geographical, and temporal limitations.

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids.

Considering early-stage drug discovery programs, the Ugi four-component reaction is a valuable, flexible, and pivotal tool, facilitating the creation of two new amide bonds in a one-pot fashion to effectively yield the desired α-aminoacylamides. Here, we highlight the reputation of this reaction approach to access number and scaffold diversity of a library of isatin-based α-acetamide carboxamide oxindole hybrids, promising anticancer agents, in a mild and fast sustainable reaction process. The library was tested against six human solid tumor cell lines, among them, non-small cell lung carcinoma, cervical adenocarcinoma, breast cancer and colon adenocarcinoma. The most potent compounds 8d, 8h and 8k showed GI50 values in the range of 1-10 µM.

A sperm whale cautionary tale about estimating acoustic cue rates for deep divers.

Passive acoustic density estimation has been gaining traction in recent years. Cue counting uses detected acoustic cues to estimate animal abundance. A cue rate, the number of acoustic cues produced per animal per unit time, is required to convert cue density into animal density. Cue rate information can be obtained from animal borne acoustic tags. For deep divers, like beaked whales, data have been analyzed considering deep dive cycles as a natural sampling unit, based on either weighted averages or generalized estimating equations. Using a sperm whale DTAG (sound-and-orientation recording tag) example we compare different approaches of estimating cue rate from acoustic tags illustrating that both approaches used before might introduce biases and suggest that the natural unit of analysis should be the whole duration of the tag itself.

Evaluation of chromane derivatives: Promising privileged scaffolds for lead discovery within Alzheimer's disease.

The chromane ring system is widely distributed in nature and has proven to be a highly potent pharmacophore in medicinal chemistry, which includes the area of Alzheimer's and Parkinson's diseases. We report on the development of a gem-dimethylchroman-4-ol family that was shown to give good inhibition of equine serum butyrylcholinesterase (eqBuChE) (in the range 2.9 - 7.3 µM) and in the same range of currently used drugs. We also synthesized a small library of gem-dimethylchroman-4-amine compounds, via a simple reductive amination of the corresponding chromanone precursor, that were also selective for eqBuChE presenting inhibitions in the range 7.6 - 67 µM. Kinetic studies revealed that they were mixed inhibitors. Insights into their mechanism of action were obtained through molecular docking and STD-NMR experiments, and the most active examples showed excellent drug-likeness and pharmacological properties predicted using Swiss-ADME. We also prepared a set of propargyl gem-dimethylchromanamines, for monoamine oxidase (MAO) inhibition but they were only moderately active (the best being 28% inhibition at 1 µM on MAO-B). Overall, our compounds were found to be best suited as inhibitors for BuChE.

Engaging Isatins in Multicomponent Reactions (MCRs) - Easy Access to Structural Diversity.

Multicomponent reactions (MCRs) are a valuable tool in diversity-oriented synthesis. Its application to privileged structures is gaining relevance in the fields of organic and medicinal chemistry. Isatin, due to its unique reactivity, can undergo different MCRs, affording multiple interesting scaffolds, namely oxindole-derivatives (including spirooxindoles, bis-oxindoles and 3,3-disubstituted oxindoles) and even, under certain conditions, ring-opening reactions occur that leads to other heterocyclic compounds. Over the past few years, new methodologies have been described for the application of this important and easily available starting material in MCRs. In this review, we explore these novelties, displaying them according to the structure of the final products obtained.

N-1,2,3-triazole-isatin derivatives for cholinesterase and ß-amyloid aggregation inhibition: A comprehensive bioassay study.

Our goal was the evaluation of a series of N-1,2,3-triazole-isatin derivatives for multi-target activity which included cholinesterase (ChE) inhibition and ß-amyloid (Aß) peptide anti-aggregation. The compounds have shown considerable promise as butyrylcholinesterase (BuChE) inhibitors. Although the inhibition of eel acetylcholinesterase (eeAChE) was weak, the inhibitions against equine BuChE (eqBuChE) and human BuChE (hBuChE) were more significant with a best inhibition against eqBuChE of 0.46 µM. In some cases, these molecules gave better inhibitions for hBuChE than eqBuChE. For greater insights into their mode of action, molecular docking studies were carried out, followed by STD-NMR validation. In addition, some of these compounds showed weak Aß anti-aggregation activity. Hepatotoxicity studies showed that they were non-hepatoxic and neurotoxicity studies using neurite outgrowth experiments led to the conclusion that these compounds are only weakly neurotoxic.

MicroRNA-196a is regulated by ER and is a prognostic biomarker in ER+ breast cancer.

BACKGROUND: MicroRNAs are potent post-transcriptional regulators involved in all hallmarks of cancer. Mir-196a is transcribed from two loci and has been implicated in a wide range of developmental and pathogenic processes, with targets including Hox, Fox, Cdk inhibitors and annexins. Genetic variants and altered expression of MIR196A are associated with risk and progression of multiple cancers including breast cancer, however little is known about the regulation of the genes encoding this miRNA, nor the impact of variants therein. METHODS: Genomic data and chromatin interaction analysis were used to discover functional promoter and enhancer elements for MIR196A. Expression data were used to associate MIR196A with mechanisms of resistance, breast cancer subtypes and prognosis. RESULTS: Here we demonstrate that MIR196A displays complex and dynamic expression patterns, in part controlled by long-range transcriptional regulation between promoter and enhancer elements bound by ERα. Expression of this miRNA is significantly increased in drug-resistant models of hormone-receptor positive disease. The expression of MIR196A also proves to be a robust prognostic factor for patients with advanced and post-menopausal ER+ disease. CONCLUSION: This work sheds light on the normal and abnormal regulation of MIR196A and provides a novel stratification method for therapeutically resistant breast cancer.

New cholinesterase inhibitors for Alzheimer's disease: Structure Activity Studies (SARs) and molecular docking of isoquinolone and azepanone derivatives.

A library of isoquinolinone and azepanone derivatives were screened for both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity. The strategy adopted included (a) in vitro biological assays, against eel AChE (EeAChE) and equine serum BuChE (EqBuChE) in order to determine the compounds IC50 and their dose-response activity, consolidated by (b) molecular docking studies to evaluate the docking poses and interatomic interactions in the case of the hit compounds, validated by STD-NMR studies. Compound (1f) was identified as one of these hits with an IC50 of 89.5µM for EeAChE and 153.8µM for EqBuChE, (2a) was identified as a second hit with an IC50 of 108.4µM (EeAChE) and 277.8µM (EqBuChE). In order to gain insights into the binding mode and principle active site interactions of these molecules, (R)-(1f) along with 3 other analogues (also as the R-enantiomer) were docked into both RhAChE and hBuChE models. Galantamine was used as the benchmark. The docking study was validated by performing an STD-NMR study of (1f) with EeAChE using galantamine as the benchmark.

Effectiveness of the Language Intervention Programme for Preschool Children.

OBJECTIVE: This paper investigates the effectiveness of the Language Intervention Programme for the treatment of 14 preschool-aged children with primary language impairment. PATIENTS AND METHODS: We used a waiting list control design, in which half the sample (7 children) received immediate intervention with the Language Intervention Programme, whereas the remaining children received treatment after a 4-week delay. The intervention consisted of 8 individual biweekly sessions. Outcome measures of language ability (receptive semantic and morphosyntactic, expressive semantic and morphosyntactic, and metalinguistic) were taken before and after intervention. RESULTS: After 4 weeks of intervention, the experimental group showed significant improvements in language (receptive, expressive and metalinguistic skills), but no differences were found for those in the waiting control group. After 4 weeks of intervention for the control group, significant progress in language was also observed. CONCLUSION: The Language Intervention Programme was found to be effective in treating language skills of children with language impairment, providing clinical evidence for speech and language therapists to employ this programme for the treatment of preschool children with language disorders.

Evaluating the Quality of Systematic Reviews on Pediatric Sedation in Dentistry: An Umbrella Review.

Sedation is a depression of a patient's state of consciousness, induced by medications, that can reach different levels of intensity during a medical procedure. Conscious sedation produces a minimally depressed level of consciousness without impairment of the ability to maintain an open airway, of protective reflexes or of responses to verbal and physical stimulation. This umbrella review is aimed at critically assessing the available systematic reviews (SRs) and meta-analyses (MA) on sedation in children/adolescents. An electronic database search was conducted that included Pubmed-Medline, Web of Science, Cochrane, Scopus, Scielo, Embase, LILACS and TRIP and the scope of which extended until January 2023. The risk of bias (RoB) of SRs was analyzed using the Measurement Tool to Assess SRs criteria 2 (AMSTAR2). Of 998 entries, 37 SRs were included. In terms of methodological quality, eight studies were assessed as having critically low quality, four studies had low quality, nine studies had moderate quality, and sixteen were considered to be of high quality. Based on the current guidelines, the most employed drugs in pediatric dentistry for sedation are nitrous oxide and midazolam; however, the available evidence supporting their use is insufficient and of low/critically low quality. The combined technique is recommended (nitrous oxide (30-50%) + midazolam). The optimal dose of oral midazolam is 0.75 mg/kg. The level of methodological quality of SRs is expected to increase according to the results and future directions of this umbrella review.

Vacuum cleaving of superconducting niobium tips to optimize noise filtering and with adjustable gap size for scanning tunneling microscopy.

Superconducting (SC) tips for scanning tunneling microscopy (STM) can enhance a wide range of surface science studies because they offer exquisite energy resolution, allow the study of Josephson tunneling, or provide spatial contrast based on the local interaction of the SC tip with the sample. The appeal of a SC tip is also practical. An SC gap can be used to characterize and optimize the noise of a low-temperature apparatus. Unlike typical samples, SC tips can be made with less ordered materials, such as from SC polycrystalline wires or by coating a normal metal tip with a superconductor. Those recipes either require additional laboratory infrastructure or are carried out in ambient conditions, leaving an oxidized tip behind. Here, we revisit the vacuum cleaving of an Nb wire to prepare fully gapped tips in an accessible one-step procedure. To show their utility, we measure the SC gap of Nb on Au(111) to determine the base temperature of our microscope and to optimize its RF filtering. The deliberate coating of the Nb tip with Au fully suppresses the SC gap and we show how sputtering with Ar+ ions can be used to gradually recover the gap, promising tunability for tailored SC gaps sizes. • Oxide free superconducting STM tips • RF filter optimization.

Breast cancer in young women: a rising threat: A 5-year follow-up comparative study.

Introduction: Breast cancer in young women is usually considered as breast cancer occurring in women younger than 40 years and is the most frequent cancer-related cause of death in these patients. In the past few years, there seems to be an increasing trend in the prevalence of breast cancer in young women, which, associated with poorer prognosis, more aggressive histologic features, and more frequent recurrence rates, makes it a rising threat to young women. This study aimed to evaluate the biological behavior of breast cancer in young women in our institution. Material and methods: A retrospective, unicentric, cohort study was conducted between 2012 and 2016. All consecutive patients with breast cancer were enrolled in the study. Cases were divided into two groups: case group, those younger than 40 years, and control group, those 40 years or older. The exclusion criterion was nonoperative treatment. Several clinical and pathologic parameters were evaluated, as well as were overall survival time and disease-free survival time. Results: The incidence of breast cancer in young women presented a rising tendency over the study period. Significant differences were observed in the comparison of the groups according to body mass index, age at menarche, age at birth of the first child, and proliferation rate. There were no differences in overall survival and disease-free survival rates between the groups. Conclusions: Young women had a more symptomatic presentation, a greater tumor proliferation rate, but similar outcomes compared with older patients. Greater multicentric studies are needed to confirm or refute these results.

Molecular profile of patients with myelofibrosis: a 10-year experience.

OBJECTIVE: To analyze the karyotype test and myeloid panel with next-generation sequencing findings in patients with myelofibrosis, and to compare transplant characteristics in patients referred for bone marrow transplantation. METHODS: Retrospective, single-center study with patients diagnosed with myelofibrosis treated at Hospital Israelita Albert Einstein between 2010 and 2020. RESULTS: A total of 104 patients with myelofibrosis were examined. Patients who had not been submitted to tests in our service were excluded. The final sample comprised 69 patients. Of these 69, 56 were submitted to karyotyping and 22 to myeloid panel with next-generation sequencing. Karyotype was normal in 60% of the patients and altered in 40%. The prevalence of high-risk molecular mutations was higher in patients referred for bone marrow transplantation (100% versus 50%). The median follow-up of transplant patients was 2.4 years and the overall survival at 2 years was 80% (95%CI: 62-100%). CONCLUSION: The molecular analysis enables estimating the patient's risk and thus instituting more aggressive treatment such as bone marrow transplant for patients at higher risk, being a relevant tool to guide therapy. Given the significance of molecular analysis for therapeutic decision-making in myelofibrosis, collection and disclosure of data on the prevalence of cytogenetic changes and findings of next-generation sequencing in affected patients is important.

Toxicity assessment of various ionic liquid families towards Vibrio fischeri marine bacteria.

The increasing interest on the application of ionic liquids (ILs) to a wide range of processes and products has been hampered by a lack of toxicological data, mainly in what concerns novel cations, such as guanidinium, phosphonium, and functionalized and non-functionalized imidazolium-based ILs. The present study reports the toxicity of five guanidinium-, six phosphonium, and six imidazolium-based ILs, towards the luminescent marine bacteria Vibrio fischeri. These new results clearly show that guanidinium-, unlike the imidazolium- and phosphonium-based ILs, do not follow the trend of increasing toxicity with the increase in the alkyl chain length. Moreover, the introduction of oxygenated groups on the alkyl chains, such as ether and ester, leads to a decrease of the toxicity of guanidinium and also imidazolium compounds. In what respects the effect of the different cations, it is possible to recognize that the phosphonium-based ILs seem to be more toxic when compared to the analog imidazolium-based ILs (with the same anion and alkyl chains).

Aeromonas spp. Prevalence, Virulence, and Antimicrobial Resistance in an Ex Situ Program for Threatened Freshwater Fish-A Pilot Study with Protective Measures.

Ex situ breeding programs are important conservation tools for endangered freshwater fish. However, developing husbandry techniques that decrease the likelihood of disease, antimicrobial resistance, and virulence determinants acquisition during this process is challenging. In this pilot study, we conducted a captivity experiment with Portuguese nase (Iberochondrostoma lusitanicum), a critically endangered leuciscid species, to investigate the influence of simple protective measures (i.e., material disinfection protocols and animal handling with gloves) on the dynamics of a potential pathogenic genus, Aeromonas, as well as its virulence profiles and antimicrobial resistance signatures. Our findings show that antimicrobial resistance in Aeromonas spp. collected from I. lusitanicum significantly increased during the extent of the assay (5 weeks), with all isolates collected at the end of the study classified as multidrug-resistant. Additionally, humans handling fishes without protective measures were colonized by Aeromonas spp. The use of protective measures suggested a decreasing trend in Aeromonas spp. prevalence in I. lusitanicum, while bacterial isolates displayed significantly lower virulence index values when virulence phenotypical expression was tested at 22 °C. Despite this study representing an initial trial, which needs support from further research, protective measures tested are considered a simple tool to be applied in ex situ breeding programs for aquatic animals worldwide. Furthermore, current results raise concern regarding antimicrobial resistance amplification and zoonotic transmission of Aeromonas spp. in aquatic ex situ programs.

Patulin in tomatoes and the inhibitory capacity of their phenolic extracts against Penicillium expansum.

This study aimed to determine Patulin (PAT) in samples of organically and conventionally grown tomato varieties, to correlate it with their phenolic profile and at evaluating effects of phenolic extracts of tomato samples against the Penicillium expansum CCT 7549 strain. Four varieties of tomatoes (Cherry, Khaki, Italian and Long Life) subject to conventional and organic management were collected in markets in the south of Brazil. PAT was determined in samples by validated method Matrix Solid Phase Dispersion (MSPD) with detection in HPLC-PDA. Titratable acidity, phenolic profile and antifungal activity (minimum inhibitory concentration - MIC and minimum fungicidal concentration - MFC) against P. expansum were determined. In most tomatoes PAT was found at levels that were below the Maximum Recommended Level (MRL = 50 µg/kg). Samples of conventionally grown Cherry tomato showed high acidity and PAT contamination, whose correlation was confirmed by the Principal Component Analysis (PCA). Phenolic extracts of tomatoes subject to conventional management were more efficient to inhibit P. expansum, a fact that may be explained by the content of caffeic acid. However, since PAT production was not inhibited in fruit, it is recommended that PAT should be monitored and a new management strategy should be investigated.