Miracle-dz/UniFAR-FTUs huggingface dataset:
Cycling versus swapping strategies in psoriatic arthritis: results from the rheumatic diseases Portuguese register.

OBJECTIVE To compare the 2-year retention rate between a second tumor necrosis factor alpha inhibitor (TNFi) and secukinumab (SEK) or ustekinumab (UST), in Psoriatic Arthritis (PsA) patients with previous inadequate response to their first TNFi. METHODS Prospective longitudinal cohort study with a follow-up period of 2 years using the Nationwide Portuguese Reuma.pt database. Patients with a clinical diagnosis of PsA who also fulfill the CASPAR classification criteria, with previous treatment failure to a first-line TNFi and having started a second biotechnological drug (TNFi, SEK or UST) were included. The Cycling group was defined as switching from a first TNFi to a second TNFi, and the Swapping group as switching from a first TNFi to SEK or UST. Sociodemographic data, disease characteristics, disease activity scores and physical function at baseline and after 6, 12 and 24 months were recorded. Cox-proportional hazards regression was used to compare retention rates between Cycling and Swapping groups. To obtain a predictor model of 2-year discontinuation, a multivariable Cox regression model was performed. RESULTS In total, 439 patients were included, 58% were female, with a mean age (standard deviation) of 49 (12) years. Globally, 75.6% initiated a second TNFi (Cycling group), and 24.4% started SEK/UST (Swapping group). The retention rates after 6, 12 and 24 months were 72%/66%/59% in the Cycling group; and 77%/66%/59% in the Swapping group. There were no significant differences in retention rates between both strategies (HR: 1.06, 95% CI 0.72-1.16). After 2 years of follow-up, 34.4% of patients discontinued their second biologic, mainly due to inefficacy (72.8%), with no differences found between groups. Baseline treatment with glucocorticoids was the only predictor of discontinuation after 2 years of follow-up (HR:1.668, 95% CI 1.154-2.409). CONCLUSIONS After failure of a first TNF inhibitor, Cycling and Swapping strategies result in similar retention rates suggesting that both are acceptable in the management of patients with psoriatic arthritis.
Recent insights on the clinical, pathological, and molecular features of intraductal carcinoma of the prostate

Intraductal carcinoma of the prostate, a unique histopathologic entity that is often observed (especially in advanced prostate cancer), is characterized by the proliferation of malignant cells within normal acini or ducts surrounded by a basement membrane. Intraductal carcinoma of the prostate is almost invariably associated with an adjacent high‐grade carcinoma and is occasionally observed as an isolated subtype. Intraductal carcinoma of the prostate has been demonstrated to be an independent poor prognostic factor for all stages of cancer, whether localized, de novo metastatic, or castration‐resistant. It also has a characteristic genetic profile, including high genomic instability. Recognizing and differentiating it from other pathologies is therefore important in patient management, and morphological diagnostic criteria for intraductal carcinoma of the prostate have been established. This review summarizes and outlines the clinical and pathological features, differential diagnosis, molecular aspects, and management of intraductal carcinoma of the prostate, as described in previous studies. We also present a discussion and future perspectives regarding intraductal carcinoma of the prostate.
Long follow-up of BNT162b2 mRNA vaccine in healthcare workers (2020–2022): A retrospective longitudinal SARS-CoV-2 serological surveillance

ABSTRACT SARS-CoV-2 anti-spike IgG production and protection from severe respiratory illness should be explored in greater depth after COVID-19 booster vaccination. This longitudinal observational retrospective study investigated the anti-spike IgG response elicited by the first, second and booster doses of BNT162b2 mRNA vaccine in healthcare workers (HCW) at San Martino IRCCS Policlinico Hospital (Genoa) up to the 12th month. Sequential blood sampling was performed at T0 (prior to vaccination), T1 (21 days after the 1st dose of vaccine), T2, T3, T4, T5, T6 (7 days and 1, 3, 6 and 9 months after the 2nd dose, respectively), T7 and T8 (1 and 3 months after a booster dose). A SARS-CoV-2 IgG panel (Bio-Rad, Marnes-la-Coquette, France) was used to determine levels of receptor-binding domain (RBD), spike-1 (S1), spike-2 and nucleocapsid structural proteins of SARS-CoV-2. In the 51 HCWs evaluated, seroprevalence was 96% (49/51) at T1 and 100% (51/51) from T2 to T5 for RBD and S1. At T6, only one HCW was negative. T2 [RBD = 2945 (IQR:1693–5364); S1 = 1574 (IQR:833–3256) U/mL], and T7 [RBD = 8204 (IQR:4129–11,912); S1 = 4124 (IQR:2124–6326) U/mL] were characterized by the highest antibody values. Significant humoral increases in RBD and S1 were documented at T7 and T8 compared to T2 and T4, respectively (p-value < .001). Following vaccination with BNT162b2 and a booster dose in the 9th month, naïve and healthy subjects show high antibody titers up to 12 months and a protective humoral response against COVID-19 disease lasting up to 20 months after the last booster.
Distance- and Velocity-Based Simultaneous Obstacle Avoidance and Target Tracking for Multiple Wheeled Mobile Robots

This paper proposes the distance- and velocity-based simultaneous obstacle avoidance and target tracking (DV-SOATT) method for the trajectory tracking problem of multiple wheeled mobile robots (MWMRs) operating in a shared workspace based on the relative positions and velocities of the wheeled mobile robots (WMRs) and their encountered obstacles. Compared to the previous arts considered only their relative positions, the DV-SOATT method that adds an auxiliary velocity vector lessens needless activation of the collision avoidance maneuvers, where the DV-SOATT introduces radial bounds for forecasting a collision. We provide two decision criteria for the addition of the auxiliary velocity term and compare the DV-SOATT method with the original method proposed by Li et al. (2021). The problem of the WMRs pause from the path conflict is addressed. Bound constraints on MWMRs’ velocities are considered to restrict the movement speed of the robot so as to ensure smoothness. The control law is built on Lagrange multipliers on basis of constructing a quadratic programming problem. Slack variables are discarded. Bound constraints on optimization variables are included in the piecewise-linear projection function. The stability of the control law, together with the efficiency of the DV-SOATT method, is discussed based on the Lyapunov function. The efficiency is tested on multiple omnidirectional Mecanum-wheeled mobile robots and validated through physical experiments and simulation.
Temporal Reinforcement of Naloxone Training Results in Significant Retention of Anti-bias and Overdose-Response Knowledge

Background: The opioid epidemic is an increasingly severe problem affecting public health and leading to significant economic burdens on healthcare systems. Overdose reversal training and de-stigmatization efforts are common strategies used to combat this epidemic. Nevertheless, healthcare professionals report a lack of confidence in administering naloxone and high stigmatization levels toward people with opioid use disorder (OUD). While one-time educational training reduces stigma and improves naloxone administration confidence, we previously demonstrated that knowledge retention at a three-month follow-up is reduced among a cohort of medical students. This study aimed to improve the effectiveness of opioid overdose awareness and reversal training (OOART) with a three-month follow-up abbreviated OOART (aOOART) booster video. Methods: Voluntary OOART was offered to first-year medical students (M1) at the Drexel University College of Medicine in 2022. At this training, 82 students completed a pre-training survey to establish a baseline knowledge and attitude toward people with OUD and their familiarity with the steps to reverse an opioid overdose. Following the hour-long training, 64 of 82 (79%) participants completed the post-training survey to measure the immediate retention of training information. After 2.5 months, students were randomly selected to receive a 6.5-minute aOOART booster video or serve as an unboosted control. Students in the booster and non-booster cohorts then completed a three-month follow-up survey. Results: Students who received the aOOART booster had significantly increased opioid reversal knowledge scores compared to non-boosted control students at the three-month follow-up. The aOOART booster resulted in a retention of the lowered stigma, and participants expressed a higher willingness to respond to an opioid overdose compared to participants who did not receive the booster video at the three-month follow-up. Conclusions: This study shows that an aOOART booster method improves knowledge retention following initial OOART. Further, the aOOART booster video served to maintain participants’ reduced stigma toward people with OUD and maintained participants’ willingness to respond to an opioid overdose. These results support the incorporation of an abbreviated, periodic OOART reinforcement video into opioid overdose response training nationwide. We believe this “booster video” approach is a novel and effective method to improve healthcare professionals’ and medical student preparedness to render appropriate care to people with OUD.
Determinants of International Migration: A Global Analysis

This paper addresses the determinants of migration between countries. Special emphasis is placed on which factors attract immigrants. This paper is the first to analyse this question in an integrated framework that takes into account the characteristics of both the origin and destination countries of migration. The findings confirm previous findings, however, in a broader and more compelling frame given the study’s unique dyadic approach to the analysis of migration patterns. Migrants are more attracted to countries with a common colonial history but, then, among these, prefer countries that offer the better living conditions and rule of law.
Spatial Snow Cover Processes at Kühtai and Reynolds Creek

In many climates, predicting and understanding the spatio-temporal variability of snow-related quantities plays a key role in catchment hydrology. Practical applications include the prediction of snowmelt induced floods and the estimation of water yield from snow-covered catchments for water resources management. The snow cover is also a key link in the climate system via its effect on the surface energy and water balance, so its accurate representation is essential to a better understanding of climate effects on the hydrological cycle. Modelling the spatio-temporal variability of snow-related quantities is complicated by the interrelated and multiscale nature of the processes involved. Natural snow variability is extreme and although snow related data such as snow water equivalent is often available in considerable temporal detail as time series (e.g. the US SNOTEL network, NRCS, 1998), the spatial resolution of snow-related data is notoriously poor. Often, at best, a few point measurements are available in the catchment of interest and, because of the extreme spatial variability, point data are not very representative of the spatial patterns and/or the spatial averages. Although runoff does provide a spatially aggregated estimate of melt water yield from a catchment, it is not possible to infer the actual melt processes and their spatial distribution from runoff data alone. Recently, progress in remote sensing of snow has shown potential. Snow-covered area can be measured using a variety of methods. However, remote sensing of snow water equivalent has not been sufficiently developed for operational observation of deep snowcover in rugged mountain terrain (Elder et al., 1998). Therefore it has been suggested in the literature (e.g., Bloschl et al., 1991b) to use snow cover patterns for evaluating and improving distributed snow models. This is consistent with the general thrust of this book of using observed patterns for assessing distributed models. As compared to other components of the hydrologic cycle described in this book such as rainfall, runoff and soil moisture, snow has the definite advantage that
Effects of natural products on cisplatin ototoxicity and chemotherapeutic efficacy

ABSTRACT Introduction Cisplatin is a very effective chemotherapeutic agent against a variety of solid tumors. Unfortunately, cisplatin causes permanent sensorineural hearing loss in at least two-thirds of patients treated. There are no FDA approved drugs to prevent this serious side effect. Areas covered This paper reviews various natural products that ameliorate cisplatin ototoxicity. These compounds are strong antioxidants and anti-inflammatory agents. This review includes mostly preclinical studies but also discusses a few small clinical trials with natural products to minimize hearing loss from cisplatin chemotherapy in patients. The interactions of natural products with cisplatin in tumor-bearing animal models are highlighted. A number of natural products did not interfere with cisplatin anti-tumor efficacy and some agents actually potentiated cisplatin anti-tumor activity. Expert opinion There are a number of natural products or their derivatives that show excellent protection against cisplatin ototoxicity in preclinical studies. There is a need to insure uniform standards for purity of drugs derived from natural sources and to ensure adequate pharmacokinetics and safety of these products. Natural products that protect against cisplatin ototoxicity and augment cisplatin’s anti-tumor effects in multiple studies of tumor-bearing animals are most promising for advancement to clinical trials. The most promising natural products include honokiol, sulforaphane, and thymoquinone.
Progerin, an Aberrant Spliced Form of Lamin A, Is a Potential Therapeutic Target for HGPS

Hutchinson–Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder caused by the mutant protein progerin, which is expressed by the abnormal splicing of the LMNA gene. HGPS affects systemic levels, with the exception of cognition or brain development, in children, showing that cellular aging can occur in the short term. Studying progeria could be useful in unraveling the causes of human aging (as well as fatal age-related disorders). Elucidating the clear cause of HGPS or the development of a therapeutic medicine could improve the quality of life and extend the survival of patients. This review aimed to (i) briefly describe how progerin was discovered as the causative agent of HGPS, (ii) elucidate the puzzling observation of the absence of primary neurological disease in HGPS, (iii) present several studies showing the deleterious effects of progerin and the beneficial effects of its inhibition, and (iv) summarize research to develop a therapy for HGPS and introduce clinical trials for its treatment.
Paleomagnetism of some Lake Superior Keweenawan rocks

__________________________________________ _ Introduction ________________________________________ _ Acknowledgments ___________________________________ _ Field and laboratory techniques _______________________ _ Collection and measurement ______________________ _ Sources of error _________________________________ _ Magnetic cleaning _______________________________ _ General geology _____________________________________ _ E:eweenawPeninsula ________________________________ _ Geologic setting _________________________________ _ Description of results ____________________________ _ Portage Lake Lava Series ____________________ _ Rhyolite flows north of Lake Gogebic, Mich ____ _ Quartz porphyry north of Lake Gogebic, Mich __ _ Rhyolite intrusion in sec. 4, T. 56 N . , R. 32 W ___ _ Rhyolite intrusion in sees. 24 and 25, T. 56 N . , R. 34 W _________________________________ _ Page
Timing of ovulation in the fat‐tailed Qezel ewes after synchronization with vaginal devices containing endogenous or exogenous synthetic progestogens during out of the breeding season

Abstract Background Wide range of ovulation distribution is the main restricting factor in establishing the pregnancy following oestrus synchronization (ES) and fixed time insemination (FTI) in sheep. Objectives Determining the ovulation time (OVT) following ES with two different vaginal devices, its relation to progesterone and conception upon FTI with frozen/thawed semen. Methods Oestrus was synchronized using either controlled internal drug release (CIDR) (ewe, n = 6; ewe lamb, n = 5) or vaginal sponge (ewe, n = 6; ewe lamb, n = 5) insertion for 12 days, plus Equine chorionic gonadotropin (eCG) at devices removal (Day 0). Sizes of the ovarian follicles were measured using transvaginal probe at −12, 0 and 30–33, 53 h and continued every 3–4 h until 75 h after eCG treatment. Serum progesterone amounts were measured at −12, 0, +2 and +11. Laparoscopic FTI was done at 60.5 ± 0.5 h. Results The CIDR‐treated group initiated and completed ovulations earlier compared to sponge‐treated females (median: 64 vs. 71 h; p < 0.05). Ewe lambs were ovulated earlier compared to ewes in the sponge‐treated group (66.71 vs. 71.5; p = 0.017). Mean sizes of ovulatory follicles and corpora lutea were not affected by device types. Higher amounts of progesterone were observed in CIDR group compared to sponge‐treated group at device removal (2.68 ± 0.12 vs. 0.30 ± 0.01 ng/mL; p < 0.001). The conception was confirmed in 2/10, and 5/11 females of sponge and CIDR‐treated females, respectively. Conclusions Types of progestogens influence the OVT, and consequently the result of FTI with frozen/thawed semen. The optimum timespan for FTI should be chosen according to the device types during non‐breeding season.
Ectopic Opening of Common Bile Duct to Duodenal Bulb: A Single Tertiary Center Experience

Background: The ectopic opening of the common bile duct(CBD) into the duodenal bulb is a rare biliary anomaly. The study aimed to reveal the experience with clinical and endoscopic outcomes in these patients. Materials and Methods: This study was conducted on 57 consecutive patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for ectopic opening of the CBD into the duodenal bulb at our institution between 2010 and 2020. Results: The median age was 59 years (49 males). A total of 146 ERCP procedures were performed (once in 26 patients and 2 or more times in 31 patients). Ten patients had a history of unsuccessful ERCP in an external center. The median follow-up time was 14.6 months. All patients had a slit-like opening of the CBD into the duodenal bulb, apical stenosis, and hook-shaped distal CBD. ERCP findings were CBD stone or dilatation in 55 patients and post-cholecystectomy biliary leakage in 2 patients. Balloon dilatation was performed for apical stenosis in 7 patients and distal CBD stenosis in 26 patients. During the first ERCP session, biliary stent/nasobiliary drainage was placed in 37 patients, and CBD stones were extracted in 19 patients without stenting. Biliodigestive anastomosis was applied to 13 patients, 5 of whom had recurrent cholangitis, 7 required recurrent ERCP, and one was due to the technical difficulty of ERCP. Conclusions: Ectopic biliary opening should be remembered if the papilla cannot be seen in its usual place in a patient with apical stenosis. ERCP should be performed in experienced hands, and surgery should be considered in the need for recurrent ERCP.
Rare decays of $B_d$ mesons into four charged leptons in the Standard Model

We present first theoretical predictions for various observables related to the $\bar B_d \to \mu^+ \mu^- e^+ e^-$ decay within the framework of the Standard Model. Our study encompasses the branching ratios, differential distributions, and forward-backward leptonic asymmetries. To obtain these predictions, we account for several contributions: resonance contribution from $\rho(770)$ and significant contribution $\omega(782)$; contributions from four charmonium resonances: $\psi(3770)$, $\psi(4040)$, $\psi(4160)$, and $\psi(4415)$; additional contributions from the"tails"of $J/\psi$ and $\psi(2S)$ resonances; non-resonant contributions arising from virtual photon emission by a $b$-quark of $B_d$ meson, bremsstrahlung, and weak annihilation. In our calculations we employ the model of vector meson dominance (VMD) to assess the resonance contributions accurately. We provide the predictions for the branching ratio of the $\bar B_d \to \mu^+ \mu^- e^+ e^-$ decay both with and without the resonant contribution from $\omega(782)$.
Seeding the Infant Gut in Early Life—Effects of Maternal and Infant Seeding with Probiotics on Strain Transfer, Microbiota, and Gastrointestinal Symptoms in Healthy Breastfed Infants

We investigated the effects of two dosing regimens of two multi-strain probiotic products on the gut microbiota of breastfed infants, including the transfer of the dosed strains and clinical outcomes. In forty-seven dyads, infants were either exposed through maternal intake (MS) of Lactobacillus acidophilus LA-5, Bifidobacterium animalis subsp. lactis BB-12, Lacticaseibacillus rhamnosus LGG, and Bifidobacterium longum subsp. infantis Bifin02 from gestational week thirty-three until four weeks after birth (n = 24) or dosed directly (IS) with the same strains except for LA-5 starting within 24 h after birth until day 28 (n = 23). Infant stool samples were collected on day 0, 14, 28, and 42 after birth. Gastrointestinal symptoms were assessed by parents using an electronic diary. Microbiota composition was determined using 16S rRNA sequencing, and strain recovery was analyzed by qPCR. Notably, 100% of the IS infants were colonized with Bifin02 after 14 days as opposed to only 25% of the MS infants. Mean stool frequency was significantly lower in IS infants compared to MS infants and IS infants had softer stools on day 14, 28, and 42. A significantly steeper slope of progression of inconsolable crying and fussing was observed in MS infants compared to IS infants. In conclusion, direct infant seeding induced a faster increase in fecal bifidobacteria abundancy and Bifin02 recovery compared to dosed through the maternal intake.
Risk Analysis of the Chinese Financial Market with the Application of a Novel Hybrid Volatility Prediction Model

This paper endeavors to enhance the prediction of volatility in financial markets by developing a novel hybrid model that integrates generalized autoregressive conditional heteroskedasticity (GARCH) models and long short-term memory (LSTM) neural networks. Using high-frequency data, we first estimate realized volatility as a robust measure of volatility. We then feed the outputs of multiple GARCH models into an LSTM network, creating a hybrid model that leverages the strengths of both approaches. The predicted volatility from the hybrid model is used to generate trading strategy signals, which are subsequently used to build an investment strategy. Empirical analysis using the China Securities Index 300 (CSI300) dataset demonstrates that the hybrid model significantly improves value-at-risk (VaR) prediction performance compared to traditional GARCH models. This study’s findings have broad implications for risk management in financial markets, suggesting that hybrid models incorporating mathematical models and economic mechanisms can enhance derivative pricing, portfolio risk management, hedging transactions, and systemic risk early-warning systems.