Miracle-dz/UniFAR-FTUs huggingface dataset:
Concomitant Proton Pump Inhibitor Use and Survival in Urothelial Carcinoma Treated with Atezolizumab

Purpose: Emerging evidence indicates that gut microbiota dysbiosis can reduce the effectiveness of immune checkpoint inhibitors (ICI). Proton pump inhibitors (PPI) are known to induce gut microbiota changes. However, little is known on the effects of PPIs on outcomes with ICI therapy, and it has not been explored in urothelial cancer treatment. Experimental Design: Individual–participant data from the advanced urothelial cancer trials, IMvigor210 (single-arm atezolizumab trial, n = 429) and IMvigor211 (phase III randomized trial of atezolizumab vs. chemotherapy, n = 931) were pooled in a Cox proportional hazard analysis assessing the association between PPI use and overall survival (OS) and progression-free survival (PFS). PPI use was defined as any PPI administration between 30 days prior and 30 days after treatment initiation. Results: Of the 1,360 participants, 471 (35%) received a PPI within the 60-day window. PPI use was associated with significantly worse OS [HR (95% confidence interval (CI)) = 1.52 (1.27–1.83), P < 0.001] and PFS [1.38 (1.18–1.62), P < 0.001] with atezolizumab, but not chemotherapy (P > 0.05). In the randomized cohort of IMvigor211, the OS treatment effect [HR (95% CI)] of atezolizumab versus chemotherapy was 1.04 (0.81–1.34) for PPI users, compared with 0.69 (0.56–0.84) for PPI nonusers (Pinteraction = 0.013). Similar associations were noted in the PD-L1 IC2/3 population. Conclusions: This study indicates PPI use is a negative prognostic marker in advanced urothelial carcinoma treated with ICI therapy, but not chemotherapy. Furthermore, the analysis suggests PPIs influence the magnitude of ICI efficacy, and this warrants further investigation.
Novel F8 and F9 gene variants from the PedNet hemophilia registry classified according to ACMG/AMP guidelines

In hemophilia A and B, analysis of the F8 and F9 gene variants enables carrier and prenatal diagnosis and prediction of risk for the development of inhibitors. The PedNet Registry collects clinical, genetic, and phenotypic data prospectively on more than 2000 children with hemophilia. The genetic reports of F8/F9 gene variants were classified uniformly to Human Genome Variation Society nomenclature and reevaluated using international population‐ and disease‐specific databases, literature survey and, where applicable, computational predictive programs. We report 88 novel variants in the F8 and F9 genes, 80 fulfilling criteria for Class 5 (pathogenic), six for Class 4 (likely pathogenic) and two fulfilling criteria for Class 3 (variant of unknown significance) of the American College of Medical Genetics and Genomics/Association for Molecular Pathologyguidelines together with information on the respective phenotype and inhibitor formation. The study highlights the need to reevaluate and update earlier genetic reports in hemophilia both locally but also in variant databases in light of changed nomenclature and new guidelines.
Platycodon grandiflorus Fermented Extracts Attenuate Endotoxin-Induced Acute Liver Injury in Mice

Endotoxin-induced acute liver injury is mediated by an excessive inflammatory response, hepatocellular oxidative stress, and apoptosis. Traditional medicinal plants have been used to treat various disorders. Platycodon grandifloras (PG) has been shown to be beneficial in relieving cough and asthma and to have anti-tumor, anti-inflammatory, anti-diabetic activities. The pharmacological action of PG is mainly due to saponins, flavonoids, phenolic, and other compounds. However, raw PG exhibits some side effects at high doses. Here, we extracted raw PG with varying fermentation methods and examined its anti-inflammatory effect and associated signaling kinases in Raw264.7 cells. Then, we investigated the effect of fermented black PG (FBPG) on endotoxin-induced liver injury. Mice were administered FBPG orally at 1 h before the lipopolysaccharide and D-galactosamine (LPS/GalN) injection and sacrificed after 5 h. Black PG (BPG) and FBPG showed a significant reduction in pro-inflammatory cytokines and extracellular nitric oxide (NO); p-38 and ERK signaling was involved in reducing inducible NO synthase in Raw264.7 cells. Consistently, FBPG attenuates LPS/GalN-induced liver injury; plasma ALT and AST, hepatic necrosis, pro-inflammatory cytokines, apoptosis, and lipid peroxidation were all reduced. In conclusion, PG extracts, particularly FBPG, play anti-inflammatory, antioxidant, and anti-apoptotic roles, alleviating endotoxin-induced acute liver injury. Processing raw PG into FBPG extract may be clinically useful by improving the pharmacologically active ingredients and reducing the required dosage.
Synthesis of Molecularly Imprinted Polymer for Sensitive Penicillin Determination in Milk

Abstract Penicillin G (PG) in milk is unsafe for human and is a big problem for the foods industry. Hence, the better analytical and eliminative techniques are demanded. We investigated a PG molecular imprinted polymer (MIP), which can sensitively detect and extract the PG from milk and other samples. The MIP synthesis involved a β-lactam antibiotics PG, methacrylic acid (MAA) and dimethyl formamide (DMF). Its properties were analyzed with Scatchard plot, which showed that there were two affinity sites of the PG polymer. The first equilibrium dissociation constant of the high-affinity binding sites Kd1 was 1.14 × 10−4 mol/L and the binding capacity Qmax1 was 46.01 µmol/g; the second equilibrium dissociation constant of the low-affinity binding sites Kd2 was 1.35 × 10−3 mol/L and the binding capacity Qmax2 was 72.55 µmol/g. Furthermore, two PG determination methods using the polymer were developed. The first was carried out quantitatively with a spectrophotometer and the detection limit was 1 ppm. The other one was the combination of the MIP particles with milk fermentation for PG analysis and the sensitivity was 10 ppb.
Does Hand-Dominance Matter in Non-Standard Visuomotor Transformations?

Abstract Previous nonstandard visuomotor transformation studies using variations of eye-hand coupling and decoupling tasks focused on dominant hand use. The present study expanded this work by including the non-dominant hand. Twenty-four right-hand dominant adults (M = 21 yrs.; 12 females) slid their index finger along a vertical or horizontal touchscreen to move a cursor that was always displayed in the vertical plane. In four different action-perception conditions, the finger and cursor moved either in the same plane and direction or in the other plane and/or opposite direction. Performance differed between the hands only for movement trajectory related variables but not for endpoint related measures. Across conditions the initial direction error was larger when performing with the non-dominant hand (p < 0.001). A significant hand × cursor direction × cursor plane interaction for path length (p < 0.05) revealed longer movement trajectories for the non-dominant hand compared to the dominant hand in conditions with none or one level of eye-hand decoupling, and similar hand performance when movements were made in the horizontal plane with reversed cursor direction, i.e., two eye-hand decoupling levels. Our findings suggest a non-dominant hand overall eye-hand coordination deficit for spatial planning and an inversely related deficit to the eye-hand decoupling level for trajectory execution.
Prognosis and risk factors associated with asymptomatic intracranial hemorrhage after endovascular treatment of large vessel occlusion stroke: a prospective multicenter cohort study

Asymptomatic intracranial hemorrhage (aICH) is a common occurrence after endovascular treatment (EVT) for acute ischemic stroke (AIS). The aims of this study were to address its impact on 3‐month functional outcome and to identify risk factors for aICH after EVT.
GTF2IRD1 overexpression promotes tumor progression and correlates with less CD8+ T cells infiltration in pancreatic cancer

Abstract Background: General Transcription Factor II-I Repeat Domain-Containing Protein 1 (GTF2IRD1) is a member of the GTF21 gene family, which encodes a set of multifunctional transcription factors. However, the potential function of GTF2IRD1 in pancreatic cancer (PC) still remains unknown. Study on GTF2IRD1 might provide a new insight into the carcinogenesis and therapeutics of PC. Methods: In the current study, the clinical significance and potential biological of GTF2IRD1 were evaluated by bioinformatics analysis. The oncogenic role of GTF2IRD1 in PC was also determined using in vitro studies. Possible associations between GTF2IRD1 expression and tumor immunity were analyzed using ESTIMATE algorithm and single-sample Gene Set Enrichment Analysis (ssGSEA). Results: GTF2IRD1 expression was significantly up-regulated in tumor tissues, and positively associated with higher histologic grade, higher American Joint Committee on Cancer (AJCC) stage, and worse prognosis. Function enrichment analysis demonstrated that GTF2IRD1 may be involved in pancreatic adenocarcinoma pathway, TGF-β signaling pathway, and tumor-infiltrating lymphocyte (TIL) related biological functions, such as T-cell receptor signaling pathway, leukocyte transendothelial migration, resistin as a regulator of inflammation, and regulation of leukocyte-mediated cytotoxicity. Knockdown of GTF2IRD1 expression inhibited cancer cell proliferation, colony formation, and invasion in vitro. ESTIMATE algorithm and ssGSEA demonstrated that GTF2IRD1 expression negatively correlated with the infiltration and anti-tumor activity of TILs, especially for CD8+ T cells. Conclusion: The study demonstrates that GTF2IRD1 overexpression promotes tumor progression and correlates with less CD8+ T cells infiltration in PC.
Simplified synthesis of silver nanoparticles on graphene oxide and their applications in electrocatalysis

In this work the possibility of synthesizing in situ silver nanoparticles (AgNPs) on graphene oxide (GO) surfaces without commonly used additional reducing or alkalizing agents or increased temperature was investigated. Using diverse microscopic (atomic force microscopy, transmission electron microscopy) and spectroscopic methods, it was proved that very small AgNPs were formed on GO by simple incubation for 2 h in a mixture of GO dispersion and AgNO3. The prepared nanomaterial (GO_Ag) was also assessed using electrochemical methods, and it exhibited electrochemical behavior similar to the GO_Ag nanomaterial prepared with a help of citric acid as a reducing agent. Furthermore, it was found that (i) the electrochemical reduction of the GO_Ag on the electrode surface decreased the voltammetric response even though this step increased the surface conductivity and (ii) GO_Ag can be employed for the sensing of chlorides with a detection limit of 79 μM and a linear range of up to 10 mM. It could also provide an electrochemical response toward the chloroacetanilide herbicide metazachlor. Hence, the reducing capabilities of GO were proved to be applicable for in situ synthesis of metal nanoparticles with the highest possible simplification, and the as-prepared nanomaterials could be employed for fabrication of different electrochemical sensors.
Case Report: Managing a Postgraft Keratoconus Patient with Scleral Lenses

ABSTRACT SIGNIFICANCE Because the prognosis of corneal regrafting is worse than a primary graft, it is pertinent to recognize other clinical management options to postpone the need for surgical intervention. Scleral lenses are a viable option in achieving excellent vision and comfort for post-graft patients; however, close monitoring is vital to success. PURPOSE The purpose of this study was to report a case in which a post-graft keratoconus patient can be successfully fit and refit with scleral lenses as their corneal tissue changes shape with time. Ultimately, the goal for this patient was to delay the need for regrafting procedures. CASE REPORT This case presents a 57-year-old patient who has undergone penetrating keratoplasty in both eyes secondary to keratoconus. His original corneal grafts were 15 years or older. Because of a history of graft rejection in the right eye, he had a regraft in 2004. The left eye has signs of early rejection. The patient has been a scleral lens wearer since 2008. Within the past 24 months, he has required lens adjustments and refits because his fragile corneal tissue has changed shape. Lens changes were indicated when he presented with complaints of fogging associated with redness and irritation. We continued to work closely with the patient's corneal ophthalmologist, who recommended we maximize scleral lens wear in lieu of a corneal regraft. Because of the change from an oblate to prolate cornea, fitting this patient in a scleral lens has been a challenging task. CONCLUSIONS Scleral lenses are a viable option in post-graft patients who present with ectatic changes to their corneal tissue. This patient continues to see 20/20 in each eye and comfortably wears his lenses for up to 6 hours. By fitting this patient in a scleral lens, we have been able to avoid the need for a regraft and the possible negative outcomes that can be associated.
Eggs mimicry of Common Cuckoo (Cuculus canorus) utilizing Ashy-throated Parrotbill (Paradoxornis alphonsianus) host

571158, China Abstract Polymorphism in egg coloration is prominent in the Common Cuckoo ( Cuculus canorus ) and a common host, the Ashy-throated Parrotbill ( Paradoxornis alphonsianus ). Egg polymorphism has probably evolved as a consequence of frequency-dependent selection in both host and parasite, and has, according to human vision, resulted in discrete immaculate white, pale blue and blue egg phenotypes within a single population. However, egg mimicry assessment is not always straightfor-ward, and previous studies have shown that human based comparisons applied to the coloration of bird eggs may be inadequate. Here, we objectively quantify egg color of both parasite and host by spectrophotometry and assess egg mimicry of the Common Cuckoo to the eggs of its Ashy-throated Parrotbill host. Our results revealed that egg reflectance spectra agree well with the assessment based on human vision that cuckoo eggs mimic those of the parrotbill host, in both visible (VIS) and ultraviolet (UV) ranges. However, the white cuckoo egg shows slightly poorer mimicry than the blue cuckoo egg in corresponding host clutches. We suggest that the white parrotbill egg morph (and sub-sequently the whitish cuckoo egg color) may have evolved after the evolution of the blue egg morph due to strong selection from parasites in the
Are Respiratory Responses to Cold Air Exercise Different in Females Compared to Males? Implications for Exercise in Cold Air Environments

Research has shown that cold air exercise causes significant respiratory dysfunction, especially in female athletes. However, how female and male athletes respond to cold air exercise is not known. Thus, we aimed to compare acute respiratory responses (function, recovery and symptoms) in males and females after high-intensity cold air exercise. Eighteen (nine female) athletes completed two environmental chamber running trials at 0 °C and −20 °C (humidity 34 ± 5%) on different days in a randomized starting order. Spirometry was performed pre, 3, 6, 10, 15 and 20 min post. Respiratory symptoms were measured posttrial and heart rate and rating of perceived exertion were assessed during each trial. No significant differences in delta change (pre to post) were found at either temperature between sexes for FEV1, FVC, FEF50% and FEF25–75%. At −20 °C, FEV1 decreased similarly in both sexes (males: 7.5%, females: 6.3%) but not at 0 °C, p = 0.003. Postexertion respiratory function recovery and reported symptoms were not different between sexes at either temperature. These results indicate no sex-based differences in acute respiratory responses (function, recovery and symptoms) to cold air exercise. However, intense exercise at −20 °C is challenging to the respiratory system in both sexes and may lead to altered respiratory responses compared to mild winter conditions like 0 °C.
Bioactive substances in marine phytoplankton: salinity effects on growth and toxin production of the dinophyte Alexandrium ostenfeldii

Alexandrium ostenfeldii is one of the most intensely studied toxic dinophyta in the world’s oceans and coastal waters. Its toxins are highly potent neurotoxins and causatives of food intoxications by contaminated sea food. In the last few years harmful algal blooms (HAB) of A. ostenfeldii have become a recurrent phenomenon in coastal waters. In 2012 such a dense bloom occurred in the Ouwerkerkse Kreek. This creek system in The Netherlands is discharging water in the Oosterschelde estuary, a large stock of mussels, oysters and fishery. Only little information is available about this A. ostenfeldii population, both in terms of its toxin profile and concerning its physiological characteristics in a highly variable ecosystem. We used multiple isolates of a bloom population for a thorough characterization of the phycotoxin profile and its variability in the population. A total of 68 A. ostenfeldii isolates were analyzed and revealed the presence of both, paralytic shellfish toxins (PSP) and cyclic imine toxins. Whereas the relative composition of PSP-toxins, consisting of saxitoxin, gonyautoxin and C-toxins, was almost identical among isolates, cyclic imine toxins were quite diverse. We detected a total of 23 different compounds with both spirolides (mainly 13-desmethyl spirolide C) and gymnodimines (both gymnodimine A and 12-methyl gymnodimine A) present and with a high variability in cyclic imine toxin profile among all isolates. Toxin cell quota was found to range 8-fold for total PSP-toxins and 11-fold for total cyclic imine toxins. Furthermore, for one selected isolate, the impact of variable salinities from 3 to 34 on growth and toxin content was determined. With similar growth rates from 0.13 to 0.2 d-1 over a salinity range from 6 to 34, a broad salinity tolerance of the Dutch A. ostenfeldii population was demonstrated. Furthermore, toxin composition and the expression of single PSP- and cyclic imine toxins were depended on salinity. Highest toxin cell quota was observed for exceptionally low and high salinities. In addition, isolates were found to produce lytic compounds with EC50 values (i.e. the concentration of A. ostenfeldii causing 50 % cell lysis of the target species Rhodomonas salina) of about 659 cells ml-1. A comparison of lytic activity in various fractions (whole cultures, culture supernatant, cell extract) revealed that whole cultures and also cell-free supernatants were about 5-fold more lytic than cell extracts. The lytic potency was susceptible for variable salinities: at very low salinities lytic effects of extracellular compounds were larger. At very high salinities, a larger amount of lytic substances was measured inside the cells. During the toxin screening a potentially new spirolide (m/z 696) was detected. LC-MS data allowed a hypothetical characterization of the compound as 23-hydroxy-13,19-didesmethyl spirolide D. For further NMR-analyzes, A. ostenfeldii was mass cultured and a total of 140 μg of the new compound was collected.
DISCONTINUATION RATES FOLLOWING A SWITCH FROM A REFERENCE TO A BIOSIMILAR BIOLOGIC IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND Biologics have revolutionized the treatment of inflammatory bowel disease (IBD). However, these drugs had a significant influence on treatment-related costs, which resulted in the development of biosimilars. OBJECTIVE This systematic review and meta-analysis aimed to evaluate the drug discontinuation rate in the IBD population who switched from originator to biosimilars in real-world switching studies and address potential nocebo effects as reasons for drug discontinuation. METHODS Medline (via PubMed), EMBASE, Cochrane Library, and abstract databases of selected congresses were screened for reports of monoclonal antibody (mAb) switching with a minimum post-switch follow-up of >6 months or three infusions. All available information on discontinuation rates was assessed. RESULTS A total of 30 observational studies were included, involving 3,594 patients with IBD. Twenty-six studies reported a switch from infliximab to CT-P13, two studies involved a switch to SB2, and switching information was not available in two studies. The discontinuation rates were 8%, 14%, and 21% at 6, 12, and 24 months, respectively. The main reasons for drug discontinuation and their respective risks were: disease worsening (2%), remission (4%), loss of adherence (4%), adverse events (5%), and loss of response (7%). The quality of the evidence ranged from low to very low depending on the outcome analyzed. Subjective symptoms leading to drug discontinuation were infrequently reported, and the nocebo effect was clearly assessed in just one of the included papers. CONCLUSION Discontinuation rates following a switch to a biosimilar in patients with IBD increase over time. However, it was not possible to confirm the nocebo effect as a reason for discontinuation. Therefore, long-term studies evaluating the use of biosimilars to monitor adverse events and potential nocebo effects in post-marketing surveillance are still needed.
Aerobic Exercise After Left-Sided Stroke Improves Gait Speed and Endurance

Supplemental digital content is available in the text. Objective The aim of the study was to investigate the effects of aerobic exercise on individuals who have had a stroke and showed baseline scores lower than the standard scores for the 6-min and 10-meter walk tests. Design Individuals were assigned to groups according to gait performance, defined by the standard values in the 6-min and 10-meter walk tests (standard baseline score and lower baseline score), and brain injury side. Aerobic exercise, 30 mins per day, 2 times a week, for a total of 12 wks. The 6-min and 10-meter walk tests in five assessments: initial, after 4, 8, 12 wks, and 4 wks of follow-up, analyzed by multivariate analysis, with P value of less than 0.05. Results The 6-min walk test data showed an increase in endurance for lower baseline score and left-brain injury, during assessments 4, and follow-up, compared with standard baseline score (F4,84 = 14.64). Lower baseline score showed endurance increase for assessments 2, 3, 4, and follow-up compared with assessment 1 (F4,84 = 7.70). The 10-meter walk test data showed an increase in speed for lower baseline score and left-brain injury, during assessments 3, 4, and follow-up, compared with assessment 1, 4, and follow-up, compared with assessment 2 (F4,84 = 5.33). Conclusions Aerobic exercise increases gait endurance and speed in individuals who have had a stroke, with left-brain injury, and lower baseline score in the 6-min and 10-meter walk tests.