Miracle-dz/UniFAR-FTUs huggingface dataset:
Gemtuzumab ozogamicin for the treatment of acute myeloid leukemia in adults

ABSTRACT Introduction Treatment of acute myeloid leukemia (AML) has changed dramatically in the past ten years with the approval of targeted agents, the first of which was the anti-CD33 antibody-drug conjugate gemtuzumab ozogamicin (GO). Despite withdrawal from the market after accelerated approval, GO was reapproved and now has a well-established role in treating select AML patients. CD33 has proven to be an important target for drug development in AML as evidenced by the improvement in survival with GO treatment. Areas covered The review summarizes the development of GO, its mechanism of action, initial studies and approval, withdrawal from the market, and subsequent reapproval after the results of several large randomized studies became available. We also provide an overview of its current role in the treatment landscape of AML. Expert opinion Multiple phase 3 trials with GO have established a significant benefit with GO in induction therapy for favorable risk AML. Additional studies support the use of GO in relapsed/refractory AML and APL. Despite the withdrawal of GO from the market after initial approval, GO has proven to improve survival of select AML patients when added to induction chemotherapy and in relapsed disease.
Neonatal and Juvenile Ocular Development in Göttingen Minipigs and Domestic Pigs: A Histomorphological and Immunohistochemical Study

Pigs are considered one of the relevant animal models for ocular research as they share several histological and anatomical similarities with the human eye. With the increasing interest in juvenile animal models, this study aimed to describe the postnatal development of ocular structures in 16 Göttingen minipigs and 25 F2 domestic pigs, between birth and 6 months of age, using histopathology and immunohistochemistry against Ki-67, caspase-3, calbindin, glial fibrillary acidic protein, rhodopsin, and synaptophysin. All ocular structures in both pig breeds were incompletely developed at birth and for variable periods postnatally. Noteworthy histological features of immaturity included vascularization in the corneal stroma in neonatal Göttingen minipigs, increased cellularity in different substructures, remnants of the hyaloid vasculature, short and poorly ramified ciliary body processes, and a poorly developed cone inner segment. Increased cellular proliferation, highlighted by abundant Ki-67 immunolabeling, was observed in almost all developing structures of the pig eye for variable periods postnatally. Apoptosis, highlighted with caspase-3 immunolabeling, was observed in the retinal inner nuclear layer at birth and in the regressing hyaloid vasculature remnants. Immunohistochemistry against rhodopsin, synaptophysin, and calbindin demonstrated the short size of the developing photoreceptors and the immature cone inner segment morphology. Calbindin labeling revealed significant differences in the amount of positively labeled cone nuclei between the retinal area centralis and the non–area centralis regions. The elongation of Müller cell processes in the developing retina was shown with glial fibrillary acidic protein. In both pig breeds, the eyes reached histomorphological and immunohistochemical maturity at 6 months of age.
Oral mucositis after tacrolimus/sirolimus or cyclosporine/methotrexate as graft‐versus‐host disease prophylaxis

Abstract Objectives To determine whether treatment with tacrolimus plus sirolimus (Tac/Sir) as a prophylaxis for graft‐versus‐host disease worsens severe oral mucositis and delays healing compared to cyclosporine plus methotrexate (CsA/Mtx) following haematopoietic stem cell transplantation. Subjects and Methods The study comprised 141 patients: 73 randomized to receive Tac/Sir and 68 to receive CsA/Mtx. The oral mucositis assessment scale and toxicity grading according to WHO were used to assess the severity, peak and duration of oral mucositis from the day −3 to day 24 post‐transplant. Results Eighty‐seven patients developed oral mucositis in the first 24 days post‐transplant. No significant difference in oral mucositis severity between the Tac/Sir and CsA/Mtx groups was observed. The peak oral mucositis score occurred on day 10 in both groups. Although oral mucositis scores had returned to baseline in the CsA/Mtx group on day 24 post‐transplant, no significant difference compared with the Tac/Sir group was found. Conclusions The introduction of tacrolimus/sirolimus as a graft‐versus‐host disease prophylaxis in haematopoietic stem cell transplantation increased neither the incidence nor severity of oral mucositis compared with cyclosporine/methotrexate. Furthermore, oral mucositis healing was not prolonged and followed the same time pattern as cyclosporine/methotrexate.
Change in Oxidative Stress Biomarkers During 30 Days in Saturation Dive: A Pilot Study

Saturation diving allows divers to reduce the risk of decompression sickness while working at depth for prolonged periods but may increase reactive oxygen species (ROS) production. Such modifications can affect endothelial function by exacerbating oxidative stress. This study investigated the effects of saturation diving on oxidative stress damage. Redox status was evaluated through: ROS production; total antioxidant capacity (TAC); nitric oxide metabolites (NOx); nitrotyrosine (3-NT); and lipid peroxidation (8-iso-PGF2α) assessment. Creatinine and neopterin were analyzed as markers of renal function and damage. Measurements were performed on saliva and urine samples obtained at four time points: pre; deep; post; and 24 h post. Four divers were included in the study. After the saturation dive (post), significant (p < 0.05) increases in ROS (0.12 ± 0.03 vs. 0.36 ± 0.06 µmol.min−1), TAC (1.88 ± 0.03 vs. 2.01 ± 0.08 mM), NOx (207.0 ± 103.3 vs. 441.8 ± 97.3 µM), 3-NT (43.32 ± 18.03 vs. 18.64 ± 7.45 nM·L−1), and 8-iso-PGF2α (249.7 ± 45.1 vs. 371.9 ± 54.9 pg·mg−1 creatinine) were detected. Markers of renal damage were increased as well after the end of the saturation dive (creatinine 0.54 ± 0.22 vs. 2.72 ± 1.12 g-L−1; neopterin 73.3 ± 27.9 vs. 174.3 ± 20.53 μmol·mol−1 creatinine). These results could ameliorate commercial or military diving protocols or improve the understanding of symptoms caused by oxygen level elevation.
Special designed deep eutectic solvents for the recovery of high added-value products from olive leaf: a sustainable environment for bioactive materials

Abstract Deep Eutectic Solvents have been specially designed, and used for the extraction of phenolics from olive tree (Olea europea) leaves. 11 deep eutectic solvents containing a hydrogen bond donor (glycerol, ethylene glycol, lactic acid, urea, dimethyl urea and D-sorbitol) and a hydrogen bond acceptor (L-proline, citric acid, glycerol, ethylimidazole and methylimidazole) with several molar ratios have been designed. Addition of water into the solvent system increased the extraction efficiency by a remarkable difference (45%). After the best combination has been decided to extract the primary phenolic (oleuropein), operation conditions (water content in the deep eutectic solvent, speed of the homogenizer and time for the extraction) of the homogenizer-aided extraction (HAEX) for olive leaf extract has been optimized through Box-Behnken design of Response Surface Approach. The experimental yields of oleuropein, verbascoside and rutin were 15.50, 5.51 and 0.98 mg per gram dried leaf under the optimal conditions (48.9% of water in DES for 60 sec at 13310 rpm). Our best DES (citric acid/lactic acid) has yielded the most efficient extract rich in oleuropein, even with an ≈8% higher performance than that of a most commonly used solvent (75% ethanol).
Antimicrobial Resistance in Fecal Escherichia coli from Humans and Pigs at Farms at Different Levels of Intensification

The overall aim of the current study was to test the hypotheses that (i) antibiotic resistance in bacteria were more frequent in clinically health pigs in intensified company owned, medium-scale farms (MSFs) (100–500 sows) than in pigs in family-owned, small-scale farms (SSFs) (1–50 sows) and (ii) that farmers working at the MSFs were more prone to attain antibiotic resistant bacteria than farmers working at SSFs. The study was conducted in North-Eastern Thailand, comprising fecal Escherichia coli isolates from pigs, farmers working with the pigs (contact humans) and persons living in the same household as the farmer (non-contact humans) at 51 MSFs and 113 SSFs. Samples from all farms were also screened for methicillin-resistant staphylococcus aureus (MRSA), which was not detected in pig samples, but was found in one human sample. Susceptibility was tested by disc-diffusion for seven antibiotics commonly used in the study area. Resistance in pig isolates from MSFs were more frequent for chloramphenicol which (P < 0.001), trimethoprim/sulfamethoxazole (P < 0.001) and gentamicin (P < 0.05) compared with isolates from SSFs, whereas the opposite was true for tetracycline (P < 0.01). Resistance in the human isolates was lower than those in the isolates from pigs for tetracycline, trimethoprim/sulfamethoxazole and chloramphenicol (P < 0.001). The frequency of resistance in the contact human samples from SSFs and MSFs did not differ. There was no difference between isolates from contact and non-contact humans for any of the tested antibiotics. Multidrug resistance in isolates from pigs was 26%, significantly higher (P < 0.01) than the 13% from humans. The data indicate that (i) resistance to antibiotics, including those critical and highly important for human medicine, were more common in fecal E. coli from pigs at the MSFs than at the SSFs, whereas (ii) the resistance in fecal E. coli from pig farmers seemed not to be influenced by the level of intensification of the farm they were working at.
Survivorship of Cerastium atrovirens at Aberffraw, Anglesey

Very little information is available on the population dynamics of plants, even of annual species despite the fact that these pose relatively few practical problems in their study (Harper & White 1974). This paper reports a monitoring of the survivorship of Cerastium atrovirens Bab. (= C. diffusum Pers. ssp. diffusum fide C. Favarger, personal communication) from autumn germination to death of the last adults in the following May on the sand dunes at Aberffraw, Anglesey. The vegetation of the area has been described quantitatively by Pemadasa, Greig-Smith & Lovell (1974).
Reply

We thank the editor for enlightening the interest in our recent paper. We certainly agree that A-T patients suffer generally from restrictive lung disease and definitely respect former findings by McGrath-Morrow et al. and those of Verhagen et al. Nonetheless, restrictive lung disease does not contradict and may conceal existence of obstructive lung disease. Indeed we found that 11 out of 27 patients (40.7%) suffered from clinical symptoms of asthma phenotype and hyper-reactive airways, with positive response to bronchodilators (more than 10% improvement in FEV0.5 after bronchodilators). 3 The phenomenon of reversible airway function is uncommon in restrictive lung disease. Further the appearance rate of 40.7% is much higher than the 10% rate of asthmatics in the overall population. The increase in appearance rate may be due to the ineffective cough, abnormal airway secretion clearance, and recurrent aspiration, respiratory viral and bacterial infections followed with partial immune deficiency, may all lead to asthma phenotype and airway obstruction. Exploring an obstructive pattern it is rather difficult in the presence of a distinct restrictive one. A-T patients exhale all their vital capacity within a single second, reducing the sensitivity of FEV1 or FEV1/FVC and decreasing these parameters validity as an index of a positive response to bronchodilator. We therefore suggested in our work that FEV0.5 (forced expiratory volume in half a second) may be a better index for describing changes in lung function than FEV1 in AT patients. We have further recommended that a positive response to bronchodilator should include an elevation of several indices such as FEV0.5> 10% combined with elevation >20% in FEF25–75. These recommendations do not contradicts the gold standard recommendation for lung function response to bronchodilators. Our study suggests that obstructive lung disease may be common among A-T patients and the forced expiratory maneuvers may provide important information about airway disease progression. A reversible reduction in either of the indices: peak flow, FEV1 or FEV0.5, and midexpiratory flows, may be the first signs of pulmonary obstruction in these patients. Early treatment and with anti-asthma therapy, bronchodilators, and steroids, may prevent further pulmonary deterioration.
The Feasibility and Preliminary Efficacy of an eHealth Lifestyle Program in Women with Recent Gestational Diabetes Mellitus: A Pilot Study

Self-administered eHealth interventions provide a potential low-cost solution for reducing diabetes risk. The aim of this pilot randomised controlled trial (RCT) was to evaluate the feasibility, including recruitment, retention, preliminary efficacy (primary outcome) and acceptability (secondary outcome) of the “Body Balance Beyond” eHealth intervention in women with previous gestational diabetes mellitus (GDM). Women with overweight/obesity who had recent GDM (previous 24 months) were randomised into one of three groups: 1) high personalisation (access to “Body Balance Beyond” website, individual telehealth coaching via video call by a dietitian and exercise physiologist, and text message support); 2) low personalisation (website only); or 3) waitlist control. To evaluate preliminary efficacy, weight (kg), glycosylated hemoglobin, type A1C (HbA1c), cholesterol (total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL)), diet quality and moderate–vigorous physical activity were analysed at baseline and at 3 and 6 months using generalised linear mixed models. To investigate acceptability, process evaluation was conducted at 3 and 6 months. Of the 327 potential participants screened, 42 women (mean age 33.5 ± 4.0 years and BMI 32.4 ± 4.3 kg/m2) were randomised, with 30 (71%) completing the study. Retention at 6 months was 80%, 54% and 79% for high personalisation, low personalisation and waitlist control, respectively (reasons: personal/work commitments, n = 4; started weight-loss diet, n = 1; pregnant, n = 1; resources not useful, n = 1; and not contactable, n = 5). No significant group-by-time interactions were observed for preliminary efficacy outcomes, with the exception of HDL cholesterol, where a difference favoured the low personalisation group relative to the control (p = 0.028). The majority (91%) of women accessed the website in the first 3 months and 57% from 4–6 months. The website provided useful information for 95% and 92% of women at 3 and 6 months, respectively, although only a third of women found it motivating (30% and 25% at 3 and 6 months, respectively). Most women agreed that the telehealth coaching increased their confidence for improving diet (85%) and physical activity (92%) behaviours, although fewer women regarded the text messages as positive (22% and 31% for improving diet and physical activity, respectively). The majority of women (82% at 3 months and 87% at 6 months) in the high personalisation group would recommend the program to other women with GDM. Recruiting and retaining women with a recent diagnosis of GDM is challenging. The “Body Balance Beyond” website combined with telehealth coaching via video call is largely acceptable and useful for women with recent GDM. Further analysis of the effect on diabetes risk reduction in a larger study is needed.
Chicken Astrovirus (CAstV) Molecular Studies Reveal Evidence of Multiple Past Recombination Events in Sequences Originated from Clinical Samples of White Chick Syndrome (WCS) in Western Canada

In this study, we aimed to molecularly characterize 14 whole genome sequences of chicken astrovirus (CAstV) isolated from samples obtained from white chick syndrome (WCS) outbreaks in Western Canada during the period of 2014–2019. Genome sequence comparisons showed all these sequences correspond to the novel Biv group from which no confirmed representatives were published in GenBank. Molecular recombination analyses using recombination detection software (i.e., RDP5 and SimPlot) and phylogenetic analyses suggest multiple past recombination events in open reading frame (ORF)1a, ORF1b, and ORF2. Our findings suggest that recombination events and the accumulation of point mutations may have contributed to the substantial genetic variation observed in CAstV and evidenced by the current seven antigenic sub-clusters hitherto described. This is the first paper that describes recombination events in CAstV following analysis of complete CAstV sequences originated in Canada.
IX.—Stalk-eyed Crustacea Malacostraca of the Scottish National Antarctic Expedition

As the Scotia was engaged in marine research throughout the whole of its long voyage out and home, it was only to be expected that Antarctic specimens would form but a small fraction of the result. In like manner, as several of the halting-places, such as the Cape of Good Hope and the Falkland Islands, had been visited by many keen naturalists on earlier occasions, it was quite likely that species of the group with which this report is concerned would have been in numerous instances already observed. Accordingly, out of some fifty species here discriminated, only six claim to be new, and not more than ten can be regarded as Antarctic or sub-Antarctic in their place of capture. In the vast extension, however, which marine zoology has for some time past been receiving, some retardation in the stream of discovery may not be unwelcome to the systematist. Familiar forms which would otherwise amply repay a thorough reinvestigation are apt to be thrust on one side, when striking novelties are for ever appealing to be introduced. This expedition, like others before it, affords fair evidence that the Macrura are both abundant and varied in great depths of the ocean. But only too often the frailty of their fabric leaves them in a tantalisingly mutilated condition when they reach the surface.
Statistical Parametric Mapping Reveals Subtle Gender Differences in Angular Movements in Table Tennis Topspin Backhand

Background: Statistical parametric mapping (SPM) is an innovative method based on the analysis of time series (data series) and is equivalent to statistical methods for numerical (discrete) data series. This study aimed to analyze the patterns of movement in the topspin backhand stroke in table tennis and to use SPM to compare these patterns between advanced female and male players. Methods: The research involved seven advanced male and six advanced female players. The kinematic parameters were measured using an inertial motion analysis system. The SPM was computed using the SPM1D Python package. Results: Our study made it possible to reproduce the pattern of movement in the joints during topspin backhand strokes in the studied athletes. During multiple comparisons, the analysis of variance (ANOVA) SPM test revealed many areas in the studied parameter series with statistically significant differences (p ≤ 0.01). Conclusions: The study presents the movement patterns in the topspin backhand shot and describes the proximal-to-distal sequencing principle during this shot. The SPM study revealed differences between men and women in the contribution of thoracic rotation, external shoulder rotation, dorsal flexion, and supination in the wrist during the hitting phase. These differences may result from the anatomical gender differences or variations in other functionalities of individual body segments between the study groups. Another possible source for these discrepancies may reside in tactical requirements, especially the need for a more vigorous attack in men. The gender differences presented in this study can help in the individualization of the training process in table tennis.
Racial/Ethnic Discrimination, Sexual Orientation Discrimination, and Severity of Tobacco Use Disorder in the United States: Results from the National Epidemiologic Survey on Alcohol and Related Conditions-III.

INTRODUCTION Tobacco use is more prevalent among sexual minority populations relative to heterosexual populations. Discrimination is a known risk factor for tobacco use. However, the relationship between exposure to different forms of discrimination, such as racial/ethnic discrimination and sexual orientation discrimination, and tobacco use disorder (TUD) severity has not been examined. METHODS Using data from the 2012-2013 National Epidemiologic Survey of Alcohol and Related Conditions-III (n=36,309 U.S. adults), we conducted multivariable logistic regression analyses to examine the associations among racial/ethnic discrimination, sexual orientation discrimination, and TUD severity for lesbian/gay-, bisexual-, and heterosexual-identified adults. Consistent with the DSM-5, past-year moderate-to-severe TUD was defined as the presence of ≥4 DSM-5 TUD symptoms. RESULTS Higher levels of lifetime racial/ethnic discrimination were associated with significantly greater odds of past-year moderate-to-severe TUD among sexual minorities (AOR=1.03, 95% CI=1.01-1.05) and heterosexuals (AOR=1.04, 95% CI=1.03-1.05). Stressful life events, mood disorder, and anxiety disorder had significant associations with moderate-to-severe TUD among sexual minorities (AOR range: 1.86-5.22, p<.005) and heterosexuals (AOR range: 1.71-3.53, p<.005). Among sexual minorities, higher levels of racial/ethnic and/or sexual orientation discrimination were associated with greater odds of any TUD (AOR=1.02, 95% CI=1.01-1.03). CONCLUSIONS Sexual minorities and heterosexuals who experience higher levels of racial/ethnic discrimination are at heightened risk of having moderate-to-severe TUD. Exposure to higher levels of discrimination also increases the risk of having any TUD among sexual minority adults. Health providers and tobacco cessation professionals should be cognizant of the minority stressors experienced by their clients and their potential impact on TUD severity. IMPLICATIONS This study is the first to show how experiences of racial/ethnic and sexual orientation discrimination are associated with DSM-5 tobacco use disorder severity among sexual minority and heterosexual populations. Individuals exposed to multiple minority stressors may have increased vulnerability for developing tobacco use disorder and related adverse health consequences. Our study underscores the importance of considering racial/ethnic discrimination and the multiple minority statuses that individuals may hold. Eliminating all forms of discrimination and developing interventions that are sensitive to the role that discrimination plays in tobacco use disorder severity may attenuate the tobacco use disparities between sexual minority and heterosexual adults.