Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of cytogenetic abnormalities on treatment outcomes in patients with amyloid light-chain amyloidosis: subanalyses from the ANDROMEDA study

Abstract Background Cytogenetic abnormalities are common in patients with amyloid light-chain (AL) amyloidosis; some are associated with poorer outcomes. This post hoc analysis of ANDROMEDA evaluated the impact of certain cytogenetic abnormalities on outcomes in this patient population. Methods Patients with newly diagnosed AL amyloidosis were randomised 1:1 to daratumumab, bortezomib, cyclophosphamide, and dexamethasone (D-VCd) or VCd. Outcomes were evaluated in the intent-to-treat (ITT) population and in patients with t(11;14), amp1q21, del13q14, and del17p13. Results Overall, 321 patients had cytogenetic testing (D-VCd, n = 155; VCd, n = 166); most common abnormalities were t(11;14) and amp1q21. At a median follow-up of 20.3 months, haematologic complete response rates were higher with D-VCd vs VCd across all cytogenetic subgroups and organ response rates were numerically higher with D-VCd vs VCd across most subgroups. Point estimates for hazard ratio of major organ deterioration-PFS and -EFS favoured D-VCd over VCd for all cytogenetic subgroups. Deep haematologic responses (involved minus uninvolved free light chains [FLC] <10 mg/L or involved FLC ≤20 mg/L) were seen in more patients with D-VCd than VCd in all ITT and t(11;14) cohorts. Conclusions These results support the use of D-VCd as standard of care in patients with newly diagnosed AL amyloidosis regardless of cytogenetic abnormalities.
Sleep irregularity and the association with hypertension and blood pressure levels: the ELSA-Brasil study

Objective: To evaluate the associations of sleep irregularity with hypertension (HTN) and blood pressure (BP) levels. Methods: Adult participants from the ELSA-Brasil performed a clinical evaluation including objective sleep duration (actigraphy), insomnia, and a sleep study for defining obstructive sleep apnoea (OSA). To quantify sleep irregularity, we used two parameters obtained through actigraphy: 7-day standard deviation (SD) of sleep duration and 7-day SD of sleep-onset timing. A multivariate analysis was used to determine the independent associations of sleep irregularity with HTN and SBP/DBP values. Results: We studied 1720 participants (age 49 ± 8 years; 43.4% men) and 27% fulfilled the HTN diagnosis. After adjustments for age, gender, race, BMI, excessive alcohol consumption, physical activity intensity, urinary sodium excretion, insomnia, objective sleep duration and OSA (apnoea–hypopnoea index ≥15 events/h), we found that the continuous analysis of 7-day SD of sleep duration was modestly associated with prevalent HTN. However, 7-day SD of sleep duration more than 90 min was independently associated with SBP [β: 1.55; 95% confidence interval (CI) 0.23–2.88] and DBP (β: 1.07; 95% CI 0.12–2.01). Stratification analysis excluding participants with OSA revealed that a 7-day SD of sleep duration greater than 90 min was associated with a 48% higher chance of having HTN (OR: 1.48; 95% CI: 1.05–2.07). No significant associations were observed for the SD of sleep-onset timing. Conclusion: Objective measurement of sleep irregularity, evaluated by SD of sleep duration for 1 week, was associated with HTN and higher BP levels, especially in participants without OSA.
Current approaches for the treatment of ketamine‐induced cystitis

Ketamine is a dissociative anesthetic, historically used in a clinical setting for the induction and maintenance of anesthesia. Ketamine usage can produce undesirable psychological manifestations including hallucinations and long‐term psychotomimetic effects. As a results of its fast onset and short period of action, ketamine is widely used as a recreational drug. Chronic abuse of ketamine can lead to significant urinary system complications including ketamine‐induced cystitis (KIC). Common side effects of chronic ketamine abuse are urinary pain and discomfort and decreased bladder compliance and voiding pressure. Cessation of ketamine use is associated with improvement of symptoms however the exact pathophysiology of KIC remains unknown, complicating the ability of clinicians to treat this condition.
Adaptive M -estimation in nonparametric regression

A method for robust nonparametric regression is discussed. A method for robust nonparametric regression is discussed. We consider kernel M-estimates of the regression function using Huber's ψ-function and extend results of Hardle and Gasser to the case of random designs. A practical adaptive procedure is proposed consisting of simultaneously minimising a cross-validatory criterion with respect to both the smoothing parameter and a robustness parameter occurring in the ψ-function. This method is shown to possess a theoretical asymptotic optimality property, while some simulated examples confirm that the approach is practicable.
Multiple roles of released c‐type cytochromes in tuning electron transport and physiological status of Geobacter sulfurreducens

Dissimilatory metal‐reducing bacteria (DMRB) can transfer electrons to extracellular insoluble electron acceptors and play important roles in geochemical cycling, biocorrosion, environmental remediation, and bioenergy generation. c‐type cytochromes (c‐Cyts) are synthesized by DMRB and usually transported to the cell surface to form modularized electron transport conduits through protein assembly, while some of them are released as extracellularly free‐moving electron carriers in growth to promote electron transport. However, the type of these released c‐Cyts, the timing of their release, and the functions they perform have not been unrevealed yet. In this work, after characterizing the types of c‐Cyts released by Geobacter sulfurreducens under a variety of cultivation conditions, we found that these c‐Cyts accumulated up to micromolar concentrations in the surrounding medium and conserved their chemical activities. Further studies demonstrated that the presence of c‐Cyts accelerated the process of microbial extracellular electron transfer and mediated long‐distance electron transfer. In particular, the presence of c‐Cyts promoted the microbial respiration and affected the physiological state of the microbial community. In addition, c‐Cyts were observed to be adsorbed on the surface of insoluble electron acceptors and modify electron acceptors. These results reveal the overlooked multiple roles of the released c‐Cyts in acting as public goods, delivering electrons, modifying electron acceptors, and even regulating bacterial community structure in natural and artificial environments.
Skin Lesions in Children: Evaluation of Clinicopathological Findings

Objective: Pediatric skin diseases may show various manifestations, occasionally affecting the patients’ quality of life. Histopathological examination may be required for the diagnosis. The aim of this study was to evaluate the spectrum of clinicopathological features in pediatric skin lesions. Material and Methods: A total of 368 biopsies of 359 consecutive patients were included. The clinicopathological findings were retrospectively evaluated. Non-neoplastic (inflammatory) lesions (ILs) (n=186) were grouped per their origin, while neoplastic/proliferative lesions (NPLs) (n=182) were grouped based on their pattern. The clinical and histopathological characteristics were statistically analyzed. Results: 51% were male and the median age was 10.4±4.9 years (range 0-17). ILs mainly involved the head and neck, and NPLs were mostly located in the lower extremity (p<0.001). The most common NPLs were benign nevus (18%, n=33) and pilomatrixoma (15%, n=27), while the most frequent IL was spongiotic/psoriasiform dermatitis (38%). Skin appendage/connective tissue tumors were the largest among NPLs (p=0.02). NPLs were more frequently seen in children >12 years old compared to ILs (p=0.03). The discordance rate between clinical and histopathological diagnoses was higher for NPLs (27% vs. 15%). Conclusion: Although the spectrum of skin lesions is broad in pediatric patients, most are benign in nature. The higher frequency of melanocytic and/or cystic lesions among children >12 years old may be attributed to increased self-care during puberty. Neoplastic/proliferative lesions of childhood seem to be less commonly recognized by clinicians, and a multidisciplinary approach remains the optimal method, considering the relatively high rate of discordance between the clinical and histopathological diagnoses.
Visualization and wake surveys of vortical flow over a delta wing

An experimental investigation of vortex breakdown on delta wings at high angles of attack is presented. Smoke flow visualization and the laser light sheet technique were used to obtain cross-sectional views of the leading-edge vortices as they break down for a series of flat-plate delta wings having sweep angles of 70, 75, 80, and 85 deg. At low tunnel speeds (as low as 3 m/s), details of the flow that are usually imperceptible or blurred at higher speeds can be clearly seen. A combination of lateral and longitudinal cross-sectional views provides information on the three-dimensional nature of the vortex structure before, during, and after breakdown. Whereas details of the flow are identified in still photographs, the dynamic characteristics of the breakdown process have been recorded using high-speed movies. Velocity measurements have been obtained using a laser Doppler anemometer with the 70 deg delta wing at 30 deg angle of attack. The measurements show that, when breakdown occurs, the core flow is transformed from a jet-like to a wake-like flow.
Pseudoknots in RNA Structure Prediction

RNA molecules play active roles in the cell and are important for numerous applications in biotechnology and medicine. The function of an RNA molecule stems from its structure. RNA structure determination is time consuming, challenging, and expensive using experimental methods. Thus, much research has been directed at RNA structure prediction through computational means. Many of these methods focus primarily on the secondary structure of the molecule, ignoring the possibility of pseudoknotted structures. However, pseudoknots are known to play functional roles in many RNA molecules or in their method of interaction with other molecules. Improving the accuracy and efficiency of computational methods that predict pseudoknots is an ongoing challenge for single RNA molecules, RNA‐RNA interactions, and RNA‐protein interactions. To improve the accuracy of prediction, many methods focus on specific applications while restricting the length and the class of the pseudoknotted structures they can identify. In recent years, computational methods for structure prediction have begun to catch up with the impressive developments seen in biotechnology. Here, we provide a non‐comprehensive overview of available pseudoknot prediction methods and their best‐use cases. © 2023 Wiley Periodicals LLC.
Gas‐phase degradation of VOCs using supported bacteria biofilms

Herein we report the use of Pseudomonas putida F1 biofilms grown on carbonized cellulosic fibers to achieve biodegradation of airborne volatile organic compounds (VOCs) in the absence of any bulk aqueous‐phase media. It is believed that direct exposure of gaseous VOC substrates to biomass may eliminate aqueous‐phase mass transfer resistance and facilitate VOC capture and degradation. When tested with toluene vapor as a model VOC, the supported biofilm could grow optimally at 300 p.p.m. toluene and 80% relative humidity, with a specific growth rate of 0.425 day−1. During long‐term VOC biodegradation tests in a tubular packed bed reactor, biofilms achieved a toluene degradation rate of 2.5 mg gDCW−1 h−1 during the initial growth phase. Interestingly, the P. putida F1 film kept biodegrading activity even at the stationary nongrowth phase. The supported biofilms with a biomass loading of 20% (wt) could degrade toluene at a rate of 1.9 mg gDCW−1 h−1 during the stationary phase, releasing CO2 at a rate of 6.4 mg gDCW−1 h−1 at the same time (indicating 100% conversion of substrate carbon to CO2). All of these observations promised a new type of “dry” biofilm reactors for efficient degradation of toxic VOCs without involving a large amount of water.
Estrone analogs as potential inhibitors targeting EGFR‐MAPK pathway in non‐small‐cell lung cancer

Lung cancer is the deadliest human cancer globally, with non‐small‐cell lung cancer (NSCLC) being the most frequent type. Epidermal growth factor receptor (EGFR), a central regulator of tumor progression is frequently overexpressed in NSCLC and is a key drug target along with its downstream pathways. Here, we describe the biological evaluation of previously synthesized estrone analogs as potent inhibitors of NCI‐H226 cells. Two of the analogs, MMA307 and MM320, significantly inhibited the proliferation of NCI‐H226 cells with IC50 doses of 2.88 ± 0.21 and 9.68 ± 0.24 μM, respectively, compared with the positive control and chemotherapy, sorafenib, IC50 of 20.62 ± 1.32 μM. Exposing NCI‐H226 cells to IC50 concentration of MMA307 and MMA320 resulted in the downregulation of EGFR and phospho‐EGFR expression levels, and suppression of activated MAPK‐ERK1/2 signaling proteins; phospho‐B‐Raf, phospho‐MEK1/2, and phospho‐ERK1/2. Furthermore, the downregulation of cyclin D1 and concomitant upregulation of phospho‐cyclin D1 and p21waf1/cip1 were observed after the compounds' addition to NCI‐H226 cells resulting in G1 phase cell cycle arrest. MMA320 but not MMA307 downregulated the expression levels of Dyrk1B, a checkpoint kinase at the G1–S phase transition of the cell cycle. Additionally, molecular dynamic simulations were performed and found that MMA307 and MMA320 have higher binding affinities than sorafenib in MEK, BRAF, cyclin D1, and Dyrk1B (dual‐specificity tyrosine phosphorylation‐regulated kinase 1B). To conclude, the present study is the first to report on the antiproliferative potential of novel estrone analogs and provide evidence that MMA307 and MMA320 are promising novel lead candidates for the development of antilung cancer drugs.
Improving the conspicuity and safety of pedestrians and cyclists on night-time roads

ABSTRACT The visual limitations of drivers at night are a key contributing factor to the relatively high crash involvement of vulnerable road users including pedestrians, roadworkers and cyclists on night-time roads. Making vulnerable road users more conspicuous (recognisable, rather than simply visible) to oncoming drivers, is one approach to increasing their safety and has been a particular focus of my research. This review highlights the experimental approaches that our multidisciplinary research team have adopted to explore these issues, involving both closed and open road studies at night. One effective strategy to increase night-time conspicuity of vulnerable road users is clothing that includes retro-reflective materials on the moveable joints which, when illuminated in the headlight beam of oncoming vehicles, creates a strong sense of ‘biological motion’ or ‘biomotion’. Our studies demonstrated that this basic visual perception allows drivers to accurately perceive the presence of a person, such as a pedestrian or cyclist, at much longer distances than when retro-reflective materials are positioned on the torso, as in high visibility vests. Subsequent studies demonstrated that the benefits of biomotion clothing are evident in cluttered environments, in the presence of glare, and for drivers of different ages and visual characteristics. Evidence gathered in these studies was instrumental in changing Australian and New Zealand standards governing high visibility clothing for roadworkers to include retro-reflective strips in the biomotion configuration. Ongoing studies are exploring how to make biomotion clothing attractive to vulnerable road users exercising at night, and how to ensure that the limitations of night-time vision and the importance of increasing night-time conspicuity are better understood. This body of research has involved collaborators from a range of disciplines who have been essential to understanding and addressing the visual challenges of night-time roads and assisted in translating this research into tangible benefits for night-time road safety.
Identifying stem cells in the main excretory ducts of rat major salivary glands: adventures with commercial antibodies

ABSTRACT We investigated the entire length of the main excretory ducts (MED) of the major sublingual, parotid and submandibular salivary glands of mature laboratory rats for mucous (goblet) and luminal ciliated cells, biomarkers of cell proliferation, apoptosis, and five biomarkers of stem cells. Spleen and testis were used as positive controls. We used formalin fixed, paraffin embedded tissues. No mucous cells or cells with luminal cilia were observed in hematoxylin and eosin, alcian blue or periodic acid-Schiff stained sections. Immunohistochemistry using rabbit anti-rat antibodies produced anomalous reactions with cleaved caspase-3 for apoptosis, Ki-67 for proliferative activity and Sox 2. Following antigen retrieval, no primary antibody and all three negative controls, labeled macrophages appeared in the spleen. TUNEL staining revealed a few cells per section undergoing apoptosis. Reactions deemed valid occurred in MED with cytokeratin-5 and c-Kit and stem cell antigen 1 (Sca-1) mostly in the gland and middle segments. Other ducts, but not acini or myoepithelial cells, also were variably stained with c-Kit and Sca-1.
Quercetin for the treatment of COVID‐19 patients: A systematic review and meta‐analysis

Currently approved therapies for COVID‐19 are mostly limited by their low availability, high costs or the requirement of parenteral administration by trained medical personnel in an in‐hospital setting. Quercetin is a cheap and easily accessible therapeutic option for COVID‐19 patients. However, it has not been evaluated in a systematic review until now. We aimed to conduct a meta‐analysis to assess the effect of quercetin on clinical outcomes in COVID‐19 patients. Various databases including PubMed, the Cochrane Library and Embase were searched from inception until 5 October 2022 and results from six randomized controlled trials (RCTs) were pooled using a random‐effects model. All analyses were conducted using RevMan 5.4 with odds ratio (OR) as the effect measure. Quercetin decreased the risk of intensive care unit admission (OR = 0.31; 95% confidence interval (CI) 0.10–0.99) and the incidence of hospitalisation (OR = 0.25; 95% CI 0.10–0.62) but did not decrease the risk of all‐cause mortality and the rate of no recovery. Quercetin may be of benefit in COVID‐19 patients, especially if administered in its phytosome formulation which greatly enhances its bioavailability but large‐scale RCTs are needed to confirm these findings.
Incidence, Risk, and Severity of SARS-CoV-2 Reinfections in Children and Adolescents Between March 2020 and July 2022 in Serbia

Key Points Question What are the incidence, risk, and severity of SARS-CoV-2 reinfection in children and adolescents? Findings This cohort study followed up 32 524 children and adolescents with primary SARS-CoV-2 infections in Vojvodina, Serbia, for reinfections, and found that the risk of pediatric reinfection remained less than 8% approximately 2 years into the pandemic, with an incidence rate of 3.2 cases per 1000 person-months. Pediatric COVID-19 cases were generally mild, and reinfections were even milder. Meaning These findings suggest that documented reinfection risk remains substantially lower in the pediatric vs adult population, with an even more favorable profile compared with primary infections.
Prominent Staining of MYCN Immunohistochemistry Predicts a Poor Prognosis in MYCN Non-Amplified Neuroblastoma

Background: MYCN gene amplification is a powerful indicator of poor prognosis of neuroblastoma patients. However, MYCN non-amplified patients still showed heterogeneity in survival outcome. This study aimed to investigate the prognostic role of MYCN immunohistochemistry (IHC) in pre-treatment and post-treatment neuroblastoma tumors. Methods: 215 untreated neuroblastoma tumors were stained with anti-MYCN antibody by immunohistochemical staining. 22 post-treatment tumors were used to compare MYCN staining with paired pre-treatment samples. Results were analyzed with other prognostic indicators. Results: Moderate or strong expression of MYCN was associated with unfavorable survival outcomes (P < .001). Prominent staining of MYCN IHC was 95% sensitive and 95% specific for the presence of MYCN gene amplification in this study. Ten of 214 (5%) patients showed prominent MYCN staining but MYCN non-amplification, and had a poor prognosis (29.6 ± 16.4%, 5-year overall survival). Most of cases (7/11, 64%) with high or moderate MYCN expression before chemotherapy showed lower expression in their tumors after chemotherapy. Conclusion: MYCN protein overexpression was not only a sensitive and specific marker for MYCN gene amplification, but also a marker of poor prognosis in patients without MYCN amplification. However, MYCN protein expression was not always consistent before and after treatment.
Can’t catch the beat: Failure to find simple repetition effects in three types of temporal judgements

More experience results in better performance, usually. In most tasks, the more chances to learn we have, the better we are at it. This does not always appear to be the case in time perception however. In the current article, we use three different methods to investigate the role of the number of standard example durations presented on performance on three timing tasks: rhythm continuation, deviance detection, and final stimulus duration judgement. In Experiments 1a and 1b, rhythms were produced with the same accuracy whether one, two, three, or four examples of the critical duration were presented. In Experiment 2, participants were required to judge which of four stimuli had a different duration from the other three. This judgement did not depend on which of the four stimuli was the deviant one. In Experiments 3a and 3b, participants were just as accurate at judging the duration of a final stimulus in comparison to the prior stimuli regardless of the number of standards presented prior to the final stimulus. In summary, we never found any systematic effect of the number of standards presented on performance on any of the three timing tasks. In the discussion, we briefly relate these findings to three theories of time perception.