Miracle-dz/UniFAR-FTUs huggingface dataset:
An Analysis of Patient-reported Outcomes in IXORA-S: Comparing Ixekizumab and Ustekinumab over 52 Weeks in Moderate-to-severe Psoriasis

Patient-reported outcomes are valuable for assessing new psoriasis therapies. This study investigated patient-reported outcomes in patients with moderate-to-severe plaque psoriasis treated with ixekizumab or ustekinumab, dosed according to their respective labels, for 52 weeks (IXORA-S-NCT02561806). Patient-reported outcomes investigated included patient global assessment, pruritus, skin pain, health-related quality of life, and work productivity. Ixekizumab-treated patients reported greater improvements in patient-reported outcomes sooner after treatment compared with ustekinumab-treated patients, and maintained greater improvements in patient global assessment scores (ixekizumab 0.72, ustekinumab 1.19; p < 0.001), rates of Dermatology Life Quality Index (0, 1) (ixekizumab 71.3%, ustekinumab 56.6%, p < 0.01), and 36-item Short-form Health survey physical component summary score change from baseline (ixekizumab 5.53, ustekinumab 3.28; p < 0.05) at week 52. While clinically meaningful improvements in patient-reported outcomes resulted with either treatment, ixekizumab provided more rapid improvements in patient-reported outcomes and superior outcomes for some assessments through one year of treatment, while maintaining statistically superior improvements in skin severity, as assessed by either physicians or patients.
Development and Characterization of a Low-Cost Sensors System for an Acoustic Test Bench

Existing acoustic test benches are usually costly devices based on proprietary designs, sensors, and acquisition devices. In this paper, a low-cost test bench for acoustic purposes is introduced. The design of the test bench takes into account not only the low-cost mechanical design, but also uses low-cost sensors and control boards. This test bench has been designed for a range of signals compatible with those used by thermoacoustic engines, but it can be useful for applications with similar requirements. Taking advantage of an auxiliary pressure reference, low-cost unidirectional differential pressure sensors can be used to significantly increase the accuracy of the sampling system. The acoustic and mechanical design and development are presented along with the sampling system and the sensors arrangement implemented. Both the sensor and sampling system are evaluated by comparison with a high-fidelity sound acquisition system. An unexpected effect on the time error values distribution of the low-cost acquisition system is found and described. Finally, the errors introduced by the system and the sensors in terms of time and pressure sampling are characterized. As a result, the low-cost system’s accuracy has been satisfactory assessed and validated for the conditions expected in thermoacoustic experiments in terms of frequency and dynamic pressure.
Mass Occurrence of Anatoxin-a- and Dihydroanatoxin-a-Producing Tychonema sp. in Mesotrophic Reservoir Mandichosee (River Lech, Germany) as a Cause of Neurotoxicosis in Dogs

In August 2019, three dogs died after bathing in or drinking from Mandichosee, a mesotrophic reservoir of the River Lech (Germany). The dogs showed symptoms of neurotoxic poisoning and intoxication with cyanotoxins was considered. Surface blooms were not visible at the time of the incidents. Benthic Tychonema sp. , a potential anatoxin-a (ATX)-producing cyanobacterium, was detected in mats growing on the banks, as biofilm on macrophytes and later as aggregations floating on the lake surface. The dogs’ pathological examinations showed lung and liver lesions. ATX and dihydroanatoxin-a (dhATX) were detected by LC-MS/MS in the stomachs of two dogs and reached concentrations of 563 and 1207 µg/L, respectively. Anatoxins (sum of ATX and dhATX, ATXs) concentrations in field samples from Mandichosee ranged from 0.1 µg/L in the open water to 68,000 µg/L in samples containing a large amount of mat material. Other (neuro)toxic substances were not found. A molecular approach was used to detect toxin genes by PCR and to reveal the cyanobacterial community composition by sequencing. Upstream of Mandichosee, random samples were taken from other Lech reservoirs, uncovering Tychonema and ATXs at several sampling sites. Similar recent findings emphasize the importance of focusing on the investigation of benthic toxic cyanobacteria and applying appropriate monitoring strategies in the future.
Differential Advising in Multiagent Reinforcement Learning

Agent advising is one of the main approaches to improve agent learning performance by enabling agents to share advice. Existing advising methods have a common limitation that an adviser agent can offer advice to an advisee agent only if the advice is created in the same state as the advisee’s state. However, in complex environments, it is a very strong requirement that two states are the same, because a state may consist of multiple dimensions and two states being the same means that all these dimensions in the two states are correspondingly identical. Therefore, this requirement may limit the applicability of existing advising methods to complex environments. In this article, inspired by the differential privacy scheme, we propose a differential advising method that relaxes this requirement by enabling agents to use advice in a state even if the advice is created in a slightly different state. Compared with the existing methods, agents using the proposed method have more opportunity to take advice from others. This article is the first to adopt the concept of differential privacy on advising to improve agent learning performance instead of addressing security issues. The experimental results demonstrate that the proposed method is more efficient in complex environments than the existing methods.
Classification of Primary Cerebral Lymphoma and Glioblastoma Featuring Dynamic Susceptibility Contrast and Apparent Diffusion Coefficient

This study aimed to differentiate primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) via multimodal MRI featuring radiomic analysis. MRI data sets of patients with histological proven PCNSL and GBM were analyzed retrospectively. Diffusion-weighted imaging (DWI) and dynamic susceptibility contrast (DSC) perfusion imaging were evaluated to differentiate contrast enhancing intracerebral lesions. Selective (contrast enhanced tumor area with the highest mean cerebral blood volume (CBV) value) and unselective (contouring whole contrast enhanced lesion) Apparent diffusion coefficient (ADC) measurement was performed. By multivariate logistic regression, a multiparametric model was compiled and tested for its diagnostic strength. A total of 74 patients were included in our study. Selective and unselective mean and maximum ADC values, mean and maximum CBV and ratioCBV as quotient of tumor CBV and CBV in contralateral healthy white matter were significantly larger in patients with GBM than PCNSL; minimum CBV was significantly lower in GBM than in PCNSL. The highest AUC for discrimination of PCNSL and GBM was obtained for selective mean and maximum ADC, mean and maximum CBV and ratioCBV. By integrating these five in a multiparametric model 100% of the patients were classified correctly. The combination of perfusion imaging (CBV) and tumor hot-spot selective ADC measurement yields reliable radiological discrimination of PCNSL from GBM with highest accuracy and is readily available in clinical routine.
CDK4/6 inhibitors in breast cancer: differences in toxicity profiles and impact on agent choice. A systematic review and meta-analysis

ABSTRACT Introduction: CDK4/6 inhibitor approval for hormone-responsive breast tumors has significantly changed therapeutic algorithms, with three drugs currently approved. Areas covered: Here, we analyze the toxicity profiles of palbociclib, ribociclib, and abemaciclib through a systematic review and meta-analysis. Palbociclib and ribociclib showed high rates of hematological toxicity, primarily neutropenia, and were associated with a low rate of severe infections. Abemaciclib was associated with a high rate of gastrointestinal toxicities, primarily diarrhea, of grade 1–2 in most cases. Ribociclib was associated with a high rate of hepatic, and respiratory toxicity and with QTc prolongation. The toxicity rate of ribociclib was higher in metastatic patients than non-metastatic patients, with approximately 33% more grade 3–4 toxicities and 21% more grade 3–4 neutropenic events. A 5% higher risk of diarrhea was observed in postmenopausal patients. Pre-treated patients did not show a higher toxicity rate for palbociclib/ribociclib than previously untreated patients, while a 26% higher risk of any grade neutropenia and 6% higher risk of grade 3–4 diarrhea were observed with abemaciclib. Expert opinion: Considering the similar efficacies and indications of palbociclib, ribociclib, and abemaciclib, the evaluation of their toxicity profiles may facilitate treatment choice.
Clinical characteristics and treatment effects of astragalus injection in non-pediatric patients with acute fulminant myocarditis

Supplemental Digital Content is available in the text Abstract To explore the clinical characteristics of non-pediatric patients with acute fulminant myocarditis (AFM) and evaluate the treatment effects of astragalus injection on this disease. A total of 54 AFM patients were screened out from 586 patients with acute myocarditis, admitted to the department of cardiology between January 2011 to June 2018. The demographic and clinical data, investigations, treatments, and short-term outcomes were collected and retrospectively analyzed. The mean age of the 54 AFM patients was 34 ± 16.5 years old (range: 13–70 years), including 24 (44.5%) men and 30 (55.5%) women, with a high incidence in 2 age groups: 13–19 and 40–49 years old, despite an inverse trend to the increase of age. All these cases were admitted in emergency conditions: 26 (48.1%) cardiogenic shock, 18 (33.4%) malignant arrhythmias, 8 (14.8%) severe heart failure, and 2 (3.7%) acute pericardial tamponade. Apart from first-aid measures, 37 (68.5%) patients received astragalus injection. During hospitalization, 11 (20.4%) patients died, and 4 (36.3%) of them were from astragalus group while 7 (63.7%) of them from without-astragalus group (P=0.03). Furthermore, the levels of cardiac injury biomarkers, renal function and left ventricular ejection fraction of astragalus group were significantly improved compared with those of without-astragalus group at discharge (all P < .05). Middle-aged people were also prone to AFM. And cardiac shock was the most common, while acute pericardial tamponade was a rare presentation in non-pediatric AFM patients. Astragalus was a potential adjuvant medicine for the treatment of AFM.
Deep Learning for Diabetes: A Systematic Review

Diabetes is a chronic metabolic disorder that affects an estimated 463 million people worldwide. Aiming to improve the treatment of people with diabetes, digital health has been widely adopted in recent years and generated a huge amount of data that could be used for further management of this chronic disease. Taking advantage of this, approaches that use artificial intelligence and specifically deep learning, an emerging type of machine learning, have been widely adopted with promising results. In this paper, we present a comprehensive review of the applications of deep learning within the field of diabetes. We conducted a systematic literature search and identified three main areas that use this approach: diagnosis of diabetes, glucose management, and diagnosis of diabetes-related complications. The search resulted in the selection of 40 original research articles, of which we have summarized the key information about the employed learning models, development process, main outcomes, and baseline methods for performance evaluation. Among the analyzed literature, it is to be noted that various deep learning techniques and frameworks have achieved state-of-the-art performance in many diabetes-related tasks by outperforming conventional machine learning approaches. Meanwhile, we identify some limitations in the current literature, such as a lack of data availability and model interpretability. The rapid developments in deep learning and the increase in available data offer the possibility to meet these challenges in the near future and allow the widespread deployment of this technology in clinical settings.
A Deep Learning Pipeline to Automate High-Resolution Arterial Segmentation With or Without Intravenous Contrast

Background: Existing methods to reconstruct vascular structures from a computerized tomography (CT) angiogram rely on contrast injection to enhance the radio-density within the vessel lumen. However, pathological changes in the vasculature may be present that prevent accurate reconstruction. In aortic aneurysmal disease, a thrombus adherent to the aortic wall within the expanding aneurysmal sac is present in >90% of cases. These deformations prevent the automatic extraction of vital clinical information by existing image reconstruction methods. Aim: In this study, a deep learning architecture consisting of a modified U-Net with attention-gating was implemented to establish a high-throughput and automated segmentation pipeline of pathological blood vessels in CT images acquired with or without the use of a contrast agent. Methods and Results: Seventy-Five patients with paired noncontrast and contrast-enhanced CT images were randomly selected from an ongoing study (Ethics Ref 13/SC/0250), manually annotated and used for model training and evaluation. Data augmentation was implemented to diversify the training data set in a ratio of 10:1. The performance of our Attention-based U-Net in extracting both the inner (blood flow) lumen and the wall structure of the aortic aneurysm from CT angiograms was compared against a generic 3-D U-Net and displayed superior results. Implementation of this network within the aortic segmentation pipeline for both contrast and noncontrast CT images has allowed for accurate and efficient extraction of the morphological and pathological features of the entire aortic volume. Conclusions: This extraction method can be used to standardize aneurysmal disease management and sets the foundation for complex geometric and morphological analysis. Furthermore, this pipeline can be extended to other vascular pathologies.
“Excess” electrons in LuGe

Abstract The monogermanide LuGe is obtained via high‐pressure high‐temperature synthesis (5–15 GPa, 1023–1423 K). The crystal structure is solved from single‐crystal X‐ray diffraction data (structure type FeB, space group Pnma, a=7.660(2) Å, b=3.875(1) Å, and c=5.715(2) Å, RF=0.036 for 206 symmetry independent reflections). The analysis of chemical bonding applying quantum‐chemical techniques in position space was performed. It revealed—beside the expected 2c‐Ge‐Ge bonds in the germanium polyanion—rather unexpected four‐atomic bonds between lutetium atoms indicating the formation of a polycation by the excess electrons in the system Lu3+(2b)Ge2−×1 e−. Despite the reduced VEC of 3.5, lutetium monogermanide is following the extended 8‐N rule with the trend to form lutetium‐lutetium bonds utilizing the electrons left after satisfying the bonding needs in the anionic Ge‐Ge zigzag chain.
Cellulose-Based Hydrogels as Sustained Drug-Delivery Systems

Hydrogels, three-dimensional (3D) polymer networks, present unique properties, like biocompatibility, biodegradability, tunable mechanical properties, sensitivity to various stimuli, the capacity to encapsulate different therapeutic agents, and the ability of controlled release of the drugs. All these characteristics make hydrogels important candidates for diverse biomedical applications, one of them being drug delivery. The recent achievements of hydrogels as safe transport systems, with desired therapeutic effects and with minimum side effects, brought outstanding improvements in this area. Moreover, results from the utilization of hydrogels as target therapy strategies obtained in clinical trials are very encouraging for future applications. In this regard, the review summarizes the general concepts related to the types of hydrogel delivery systems, their properties, the main release mechanisms, and the administration pathways at different levels (oral, dermal, ocular, nasal, gastrointestinal tract, vaginal, and cancer therapy). After a general presentation, the review is focused on recent advances in the design, preparation and applications of innovative cellulose-based hydrogels in controlled drug delivery.
Parental vaccine attitudes, beliefs, and practices: initial evidence in California after a vaccine policy change

ABSTRACT Senate Bill 277 (SB277) eliminated nonmedical exemptions for school-entry vaccines in California, but the impact of parental vaccine knowledge, attitudes, and beliefs on vaccine decision-making has not been extensively examined within the post-SB277 context. This study generates preliminary understanding and discussion of the vaccination knowledge, attitudes, and beliefs among a pilot population of parents of kindergarten students in California after the implementation of SB277. School officials administered a cross-sectional survey to parents of kindergarten children in California from April to July 2019. Parents reported their perceptions of diseases and vaccines, key immunization beliefs, and confidence in different sources of vaccine information. Most parents (92%) had fully vaccinated their children post-SB277 and generally perceived vaccines to be safe and effective, but about 44% reported they were hesitant about childhood vaccines. The majority of parents (87%) rated vaccine information from their doctor as highly credible. This pilot group of kindergarten parents was generally supportive of vaccination and had fully vaccinated their children, but most parents still harbored concerns and misconceptions about vaccines and about public health authorities. This indicates a disconnect between parental vaccine compliance and confidence, and suggests that educational interventions could impact parental vaccine behavior and decision-making.
Toll-like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi-1 expression

Overproduction of pro-inflammatory cytokines in the aged, which is called inflammaging, leads to the deterioration of periodontitis. Toll-like receptor 4 (TLR4) plays a role in the regulation of cellular senescence, and its expression increases with age. However, there has been limited research into the molecular mechanisms underlying the onset of periodontal inflammaging, and the interplay between TLR4 and inflammaging. In the present study, wild-type and TLR4 gene knockout mice were used to investigate the activation of the TLR4 pathway in mouse periodontitis and the expression of the nucleotide-binding and oligomerization domain-like receptor 3 (NLRP3) inflammasome, an upstream immune checkpoint during the development of inflammaging. Activation of TLR4 in a mouse model of periodontitis enhanced the expression of a senescence-associated secretory phenotype (SASP), which boosted the inflammaging process. Conversely, TLR4 activation downregulated the expression of B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and promoted the priming of NLRP3 inflammasome, both of which are regulators of SASP. Treating gingival fibroblasts with Bmi-1 inhibitor PTC209, it was demonstrated that TLR4 activated the NLRP3 pathway and the inflammaging process by suppressing Bmi-1. In addition, there was a significant reduction in the expression of Bmi-1 expression in the gingiva of patients with periodontitis compared with healthy controls. In conclusion, the present study demonstrated that TLR4 acted by inhibiting Bmi-1 to enhance the NLRP3 pathway and SASP factors. This cascade of reactions may contribute to the senescence of the periodontium.
Investigation of the expression levels of CPEB4, APC, TRIP13, EIF2S3, EIF4A1, IFNg, PIK3CA and CTNNB1 genes in different stage colorectal tumors

Background/aim The aim of the study is to assess expression levels of CPEB4, APC, TRIP13, EIF2S3, EIF4A1, IFNg, PIK3CA and CTNNB1 genes in tumors and peripheral bloods of colorectal cancer patients in stages I–IV. Materials and methods The mRNA levels of the genes were determined in tumor tissues and peripheral blood samples of 45 colorectal cancer patients and colon tissues and peripheral blood samples of 5 healthy individuals. Real-time polymerase chain reaction method was used for the analysis. Results The mRNA level of the CPEB4 gene was significantly downregulated in colorectal tumor tissues and was upregulated in the peripheral blood of colorectal cancer patients relative to the controls (P < 0.05). APC mRNA level was significantly downregulated in tissues and upregulated in the peripheral blood (P < 0.05). TRIP13 mRNA level was upregulated in peripheral blood and also significantly upregulated in colorectal tumor tissues (P < 0.05). EIF2S3 mRNA level was upregulated in tissues and also significantly upregulated in peripheral blood (P < 0.05). PIK3CA mRNA level was downregulated in tissues and upregulated in peripheral blood. EIF4A1 mRNA level was downregulated in tissues and significantly upregulated in peripheral blood (P < 0.05). CTNNB1 mRNA level was downregulated in tissues and upregulated in peripheral blood. IFNg mRNA level was upregulated in both colorectal cancer tumor tissues and peripheral blood. Conclusion: TRIP13 and CPEB4 mRNA up regulation in the peripheral blood of patients with colorectal cancer may be a potential target for early stage diagnosis. In addition to this evaluation, although there is not much study on EIF2S3 and EIF4A1 mRNA changes in cases with colorectal cancer, upregulation in peripheral blood draws attention in our study. These data will shed light on the new comprehensive studies.
In Love with Shaping You—Influential Factors on the Breast Milk Content of Human Milk Oligosaccharides and Their Decisive Roles for Neonatal Development

Human milk oligosaccharides (HMOs) are structurally versatile sugar molecules constituting the third major group of soluble components in human breast milk. Based on the disaccharide lactose, the mammary glands of future and lactating mothers produce a few hundreds of different HMOs implicating that their overall anabolism utilizes rather high amounts of energy. At first sight, it therefore seems contradictory that these sugars are indigestible for infants raising the question of why such an energy-intensive molecular class evolved. However, in-depth analysis of their molecular modes of action reveals that Mother Nature created HMOs for neonatal development, protection and promotion of health. This is not solely facilitated by HMOs in their indigestible form but also by catabolites that are generated by microbial metabolism in the neonatal gut additionally qualifying HMOs as natural prebiotics. This narrative review elucidates factors influencing the HMO composition as well as physiological roles of HMOs on their way through the infant body and within the gut, where a major portion of HMOs faces microbial catabolism. Concurrently, this work summarizes in vitro, preclinical and observational as well as interventional clinical studies that analyzed potential health effects that have been demonstrated by or were related to either human milk-derived or synthetic HMOs or HMO fractions.