Miracle-dz/UniFAR-FTUs huggingface dataset:
Tolerability and efficacy of the first-in-class anti-CD47 antibody magrolimab combined with azacitidine in frontline TP53m AML patients: Phase 1b results.

7020 Background: Magrolimab is a monoclonal antibody blocking CD47, a “don’t eat me” signal overexpressed on cancer cells such as acute myeloid leukemia (AML). This blockade induces phagocytosis of tumor cells and is synergistic with azacitidine (AZA) via upregulation of “eat me” signals. We report data from a Phase 1b trial of magrolimab+AZA in frontline TP53-mutant ( TP53m) AML. Methods: Patients (pts) with frontline AML not suitable for intensive chemotherapy received IV magrolimab starting with a priming dose (1 mg/kg) followed by ramp-up to 30 mg/kg QW or Q2W as maintenance dose. AZA 75 mg/m2 was given IV or SC on Days 1–7 of each 28-day cycle. Primary endpoints were safety/tolerability and complete remission (CR) rate by ELN 2017 criteria. Results: 72 TP53m AML pts were treated (Table). Common all-grade TEAEs were constipation (52.8%), diarrhea (47.2%), febrile neutropenia (45.8%), nausea (43.1%), fatigue (37.5%), decreased appetite (37.5%), thrombocytopenia (31.9%), peripheral edema (30.6%), and cough (30.6%). Most common Grade 3+ TEAEs were febrile neutropenia (37.5%), anemia (29.2%; Grade 3, 26.4%; Grade 4, 2.8%), thrombocytopenia (29.2%), pneumonia (26.4%), and neutropenia (20.8%). Objective response rate (ORR) by intent-to-treat was 48.6% (33.3% CR, 8.3% CR with incomplete hematologic recovery [CRi] / CR with partial hematologic recovery [CRh], 1.4% morphologic leukemia-free state [MLFS], 5.6% partial response). Stable disease was reported in 16.7%, progressive disease (PD) in 5.6%. 30- and 60-day mortalities were 8.3% and 18.1%, respectively. Response assessment was unavailable in 4.2% who discontinued due to AEs and 6.9% due to other, prior to the C3D1 assessment. Median time to CR/CRi was 2.2 months (mos; range 1.7–7.2) and to CR was 3.0 mos (range 1.8–9.6). 45.2% (14/31) of evaluable CR/CRi/CRh/MLFS pts achieved negative MRD by flow cytometry (investigator reported). Of 24 CR patients, 8 had a longitudinal TP53 VAF assessment, and 5/8 (63%) had VAF decreased to ≤5%. Treatment was stopped due to SCT in 9 pts (12.5%), PD 26 (36.1%), death 8 (11.1%), AE 13 (18.1%), and other 14 (19.4%). Median durations of CR and CR/CRi were 7.7 mos (95% CI: 4.7, 10.9) and 8.7 mos (95% CI: 5.3, 10.9), respectively. Median overall survival (OS) for the 72 pts was 10.8 mos (95% CI: 6.8, 12.8) with median follow up 8.3 mos. Conclusions: In high-risk frontline TP53m AML pts unsuitable for intensive chemotherapy, magrolimab+AZA showed durable responses and encouraging OS in a single-arm study. A Phase 3 trial in TP53m AML (ENHANCE-2; NCT04778397) of this combination vs standard of care is ongoing. Clinical trial information: NCT03248479. [Table: see text]
Accelerometer-Measured Physical Activity Levels and Patterns Vary in an Age- and Sex-Dependent Fashion among Finnish Children and Adolescents

Background: The purpose of this study was to measure physical activity (PA), sedentary behavior (SB), and hour-by-hour PA patterns with an accelerometer in a population-based sample of Finnish children and adolescents. Methods: A total of 3274 participants (3rd, 5th, 7th, 9th graders) from 176 schools wore a hip-worn triaxial accelerometer for seven days during waking hours. Mean amplitude deviation of the acceleration data was used to assess PA intensity that was converted to metabolic equivalents and categorized into light, moderate, and vigorous PA. Angle for posture estimation was used to measure SB and standing. Results: The majority of participants’ PA consisted of light PA, and they were sedentary for more than half of their waking hours. Children were more active than adolescents, and boys were more active than girls. Participants took, on average, 9890 steps daily, and one third met the PA recommendation. The participants were divided into tertiles based on daily steps to investigate the variation in PA patterns. Compared to the least active tertile, the most active tertile took twice as many steps on weekdays and nearly three times as many steps on the weekend. Conclusions: The majority of the participants were not active enough, and there was a great variation in PA levels and patterns, especially among the adolescents and on weekends.
The influence of building direction and conventional heat treatment on the microstructure, physical, and mechanical characteristics of direct metal laser sintered Inconel 718 alloy

ABSTRACT DMLS fabricated IN718 alloy samples with various build orientations are analysed with heat-treatment dependent mechanical and microstructural properties. The multiple heating and cooling cycles formed a complex micro-heterogeneous microstructure composed of columnar and equiaxed subgrains in the alloy. Solution treatment resulted in a partially dissolved δ phase, and the metastable γ” phase while ageing treatment eliminated the dendritic substructure. In contrast, δ-phases precipitated mainly in the interdendritic regions, and significantly eliminated the micro-segregation and Laves phases in the γ matrix after homogenised (HSA). The tensile test showed that tensile strength decreased with increasing building orientation but ductility increased. Heat-treatment significantly improved the microhardness, ultimate tensile strength, and yield strength compared to the as-fabricated samples, but their ductility decreased. The tensile properties recorded an improvement of nearly 31.32% as compared to 0° as-built and 0° heat-treated direct aged samples. The higher microhardness (507.25 HV) was observed for the direct aged 0° build samples. The microhardness values were increased by nearly 45% after heat-treatment comparing to as-build 0° and 0° DA treated samples. The density was observed to be about 99.52% of the as-built samples, but performing the heat-treatment, no significant improvement in the density was observed and it was found similar to the as-fabricated sample.
Macular pigment optical density in a Thai sample

ABSTRACT Background The aim of this study was to determine macular pigment optical density (MPOD) and identify factors that correlate with its level in Thai subjects. Research design and methods This research was a cross-sectional study. Two hundred and forty eyes of 120 participants with healthy eyes underwent MPOD measurement using VISUCAM 500. Demographic and medical data were collected. Pearson’s correlation coefficient analyzed the relationship between the sum of optical densities (MPOD volume) and various factors. MPOD and its influencing factors were analyzed by stepwise multiple regression. Results The mean age of the participants was 50.7 ± 7.5 years. The mean MPOD was 0.102 ± 0.023 density units. The factors age (r = 0.261, p < 0.01), female gender (r = 0.191, p < 0.05), and consumption of lutein and zeaxanthin (L/Z) supplement (r = 0.168, p < 0.05) were positively associated with MPOD volume. In contrast, normal blood pressure (r = – 0.182, p < 0.05) was negatively associated with MPOD volume. No relationship with smoking, body mass index, lipid profile, and family history of AMD on MPOD values was observed in this study. Conclusions Age, gender and consumption of L/Z supplement were found to be significant predictors of MPOD in Thai subjects.
Development of an augmented reality-based process management system: The case of a natural gas power plant

Abstract Since the beginning of the Industry 4.0 era, Augmented Reality (AR) has gained significant popularity. Especially in production industries, AR has proven itself as an innovative technology renovating traditional production activities, making operators more productive and helping companies to make savings in different expense items. Despite these findings, its adoption rate is surprisingly low especially in production industries, due to various organizational and technical limitations. Various AR platforms have been proposed to eliminate this gap, however, there is still not a widely accepted framework for such a tool. This research presents the reasons behind the low adoption rate of AR in production industries, and analyzes the existing AR frameworks. Based on the findings from these analyses and a conducted field study, a cloud-based AR framework, which provides tools for creating AR applications without any coding and features for managing, monitoring and improving industrial processes is proposed. The design and development phases are presented together with the evaluation of the platform in a real-world industrial scenario.
An update on the overall epidemiology, clinical characteristics, and outcomes from the COVID-19 and Cancer Consortium (CCC19).

10565 Background: Despite mitigation and treatment strategies, COVID-19 continues to negatively impact patients (pts) with cancer. Identifying factors that remain consistently associated with morbidity and mortality is critical for risk identification and care delivery. Methods: Using CCC19 registry data through 12/31/2021 we report clinical outcomes (30-day case fatality rate [CFR], mechanical ventilation use (MV), intensive care unit admission (ICU), and hospitalization) in adult pts with cancer and laboratory confirmed SARS-CoV-2, stratified by patient, cancer, and treatment-related factors. Results: In this cohort of 11,417 pts (with 4% reported vaccination prior to COVID-19), 55% required hospitalization, 15% ICU, 9% MV, and 12% died. Overall outcome rates remained similar for 2020 and 2021 (Table). Hydroxychloroquine was utilized in 11% and other anti-COVID-19 drugs (remdesivir, tocilizumab, convalescent plasma, and/or steroids) in 30%. Higher CFRs were observed in older age, males, Black race, smoking (14%), comorbidities (pulmonary [17%], diabetes mellitus [16%], cardiovascular [19%], renal [21%]), ECOG performance status 2+ (31%), co-infection (25%), especially fungal (35%), and initial presentation with severe COVID-19 (48%). Pts with hematologic malignancy, active/progressing cancer status, or receiving systemic anti-cancer therapy within 1-3 months prior to COVID-19 also had worse CFRs. CFRs were similar across anti-cancer modalities. Other outcomes (ICU, MV, hospitalization) followed similar distributions by pt characteristics. Conclusions: Unfavorable outcome rates continue to remain high over 2 years, despite fewer case reports in 2021 owing to multiple factors (e.g., pandemic dynamics, respondent fatigue, overwhelmed healthcare systems). Pts with specific socio-demographics, performance status, comorbidities, type and status of cancer, immunosuppressive therapies, and COVID-19 severity at presentation experienced worse COVID-19 severity; and these factors should be further examined through multivariable modeling. Understanding epidemiological features, patient and cancer-related factors, and impact of anti-COVID-19 interventions can help inform risk stratification and interpretation of results from clinical trials. [Table: see text]
Learning distance functions : algorithms and applications (למידת פונקציות מרחק.)

This thesis presents research in the field of distance learning. Distance functions are extensively used in various application domains and also serve as an important building block in many types of algorithms. Despite their abundance, until recently only canonical distance functions such as the Euclidean distance have been used, or alternatively various application specific distance functions have been suggested, which in most cases were handdesigned to incorporate domain specific knowledge. In the last several years there has been a growing body of work on algorithms for learning distance functions. A considerable amount of different distance learning algorithms have been suggested, most of which aim at learning a restricted form of distance functions called Mahalanobis metrics. In this thesis I will present three novel distance learning algorithms: 1. Relevant Component Analysis (RCA) An algorithm for learning a Mahalanobis metric using positive equivalence constraints. 2. DistBoost A boosting based algorithm which can learn highly non-linear distance functions using equivalence constraints. 3. KernelBoost A variant of the DistBoost algorithm which learns Kernel functions, which can be used in any kernel-based classifier. I will then describe their applications to various data domains, which include clustering, image-retrieval, computational immunology, auditory data analysis and kernel-based classification. In all of these application domains, significant improvement is made when using a learned distance function instead of a standard off-the-shelf distance function. These results demonstrate the importance of this growing research field. The first two chapters of this work present a general introduction to the field of distance functions, and distance function learning, with some additional background on semi-supervised learning: Chapter 1 Introduction: In Chapter 1 we provide a general introduction to distance functions, and some reasons why the distance learning problem is an important and interesting learning scenario. We then provide a detailed overview of canonical and hand-designed distance functions. The algorithms presented in this thesis are all from the field of semi-supervised learning. We therefore present a short introduction to the field of semi-supervised learning, with a specific focus on learning using equivalence constraints, which is
The Mechanical Properties of in Situ Canine Skeletal Muscle

This study was undertaken to determine if fiber arrangement was responsible for differences in the whole muscle mechanical properties. Experiments were carried out in situ in blood perfused dog skeletal muscles at approximately normal body temperature between 36° and 38°C. The following mechanical relationships were studied using a pneumatic muscle lever to measure Tension (P), length (L) and dP/dt: and dL/dt with a high frequency oscillograph (500–1000 Hz): 1. ) Length:Tension; 2. ) Force:Velocity; and 3. ) Stress:Strain of Series Elastic. Electron microscopy and fiber typing were done as adjunctive studies. Muscles were stimulated by direct nerve stimulation with 0.1msec stimuli at a rate of 1 impulse per second for twitch contractions, or in 200 msec bursts of 100 Hz 0.1 msec stimuli for brief tetanic contractions. The pennate short fibered gastrocnemius plantaris developed 1.0 kg/g of tension during brief tetanic stimulation, at optimal length (Lo) with full stimulus voltage, while the parallel long fibered semitendinosus developed 0.5 kg/g under the same conditions. The Length:Tension relationship for these two muscles was qualitatively similar but quantitatively different. The Force:Velocity relationship (ΔL/L0 vs. P/P0) for both muscles were also qualitatively similar and could be described by the previously proposed rectangular hyperbola but a better predicted fit to the observed data could be produced by adding a descending exponential function to the rectangular hyperbola. Unlike previous studies, the Stress:Strain properties of the series elastic component measured by quick release (ΔL/Li vs. ΔP/Po) were linear and gastrocnemius was 25 per cent higher than the semitendinosus. Overall, both muscles were found to have mechanical properties that differed little from the previously reported literature for amphibian, cardiac and small mammalian muscles studied by others in vitro. The major differences that we found were in the shapes of the force:velocity curve of the contractile component, and the Stress:Strain curve of series elastic component. Equations and explanations for these differences are devised and presented.
Sign iconicity helps learning new words for abstract concepts in a foreign language

Several studies have explored the use of iconic gestures to improve the learning of foreign vocabulary. In this quest, words for abstract concepts have been largely neglected, under the assumption that abstract concepts have poor or non-existent sensory-motor representations. Yet, the Conceptual Metaphor Theory suggests that they are grounded on concrete concepts. Moreover, analyses of signed languages reveal ways in which signs can exploit metonymies and conceptual metaphors to iconically refer to abstract concepts. Here, we explore whether iconic signs from Spanish Sign Language (LSE) can facilitate the learning of foreign words for abstract concepts in hearing participants who do not know any sign language. In two studies, participants were presented with new labels for abstract and concrete concepts in an artificial language (Vimmi). The labels could be accompanied by either a video of an iconic or non-iconic sign taken from the existing vocabulary of LSE, or a static image of the signer. In study 1, participants did not have to enact the signs they were presented with, while in study 2 they did. Both studies showed that iconic signs facilitated the learning of abstract foreign vocabulary, regardless of enactment. The strategies that sign languages use to develop iconic signs for abstract concepts make those signs useful to assist the learning of foreign words by hearing non-signers.
BIM and Integrated Practice as Provocateurs of Design Education

Building Information Modeling (BIM) obfuscates the role of composition, scale and abstraction by displacing the primacy of abstract conventions of representation with a methodology based on simulation. BIM subverts, while simultaneously clarifying, the holistic relationships of the parts to the whole in the architectural design of form and space. Architectural design education has great opportunity and risk in how it comes to terms with re-conceptualizing design education pedagogy as the profession struggles to redefine the media and methods of architectural deliverables in the age of BIM. The paper examines the foundation issues proposed by Integrated Practice. The paper questions how BIM and modeled simulation of architectural assemblage might transcend current definitions of convention in design and construction representation. This paper explores how the academy might prepare students of architecture for a digital practice that focuses on the virtual building model and database management. BIM and Integrated Practice viewed as provocateurs of design education provide great potential for critical analysis of how architectural design is taught. The associated pedagogies are transforming the way in which architectural education engages issues of design and representation and creates opportunities to question the roles and rules of traditional conventions. The paper seeks to engage issues of design specificity and ambiguity related to the assets and liabilities of digital modeling as the primary means of design and representation that BIM represents.
Tropical Montane Cloud Forests: Meso-scale climate change in the central mountain region of Veracruz State, Mexico

Trend analyses of precipitation and fog frequency, and energy balance measurements over typical examples of forest and grassland were made in the central mountain region of the State of Veracruz in eastern Mexico to examine the possibility of meso-scale climate change. It was hypothesized that changes in precipitation and fog frequency with elevation would reflect changes in the position of the lifting condensation level (LCL) and that these could be either positive or negative, depending on site elevation. The energy balance measurements were made to quantify the changes in sensible heat flux – considered the main driving force of cloud lifting – associated with the conversion of forest to pasture. In conclusion, the observed negative tendencies in dry-season precipitation (February) and overall fog frequency at lower elevations, as well as the positive tendencies seen at intermediate and higher elevations, are in line with a postulated shift in the LCL that may have been brought about by the increase in post-forest sensible heat fluxes.
Toxicity and response to ipilimumab and nivolumab in older patients with metastatic melanoma: A multicentre retrospective analysis

Combination immunotherapy with nivolumab and ipilimumab is an effective therapy in the treatment of metastatic melanoma, however, its benefit in older patients is unclear. A multicentre retrospective study was performed to compare the efficacy and toxicity of combination immunotherapy in metastatic melanoma in patients ≥65 years versus <65 years, and complications of steroids used to manage toxicity. One hundred and thirty‐nine patients were included with 52 patients ≥65 years (median age: 70; range: 65–83) and 87 patients <65 years (median age: 52; range: 22–64). Median overall survival was similar in patients ≥65 years versus <65 years (14.9 vs. 17.3 months p = .58). Median progression‐free survival was also similar in both groups (7.1 vs. 6.9 months p = .79), as was overall response rate (48.1% vs. 44.8% p = .73). Age was not associated with a difference in overall survival on multivariate analysis. There was similar rates of Grade 3 or higher adverse events in patients ≥65 years versus <65 years (50% vs. 49% p = 1.0) and discontinuation rates secondary to toxicity (55.8% vs. 56% p = 1.0). Median duration of steroids used to treat adverse events was similar (11 vs. 12 weeks p = .46). Complications of steroids requiring inpatient admission was numerically higher in the older patients (41.3% vs. 20.4% p = .07). Patients ≥65 years received similar benefit from combination immunotherapy in comparison to their younger counterparts with similar toxicity.
Primary analysis of a phase 2, open-label, multicenter trial of talimogene laherparepvec (T-VEC) plus pembrolizumab (pembro) for the treatment (Tx) of patients (pts) with advanced melanoma (MEL) who progressed on prior anti–PD-1 therapy: MASTERKEY-115.

9518 Background: Despite advances in anti–PD-1–based Tx for MEL, an unmet need remains for immunotherapy failure in advanced metastatic or unresectable MEL. Also, there is a growing population of pts who received adjuvant anti–PD-1 and recurred; yet trials to address this population are lacking. Combination Tx with T-VEC, an oncolytic viral intratumoral Tx designed to produce GM-CSF, and pembro, an anti–PD-1 agent, may overcome immunotherapy failure. We report the MASTERKEY-115 primary analysis on the efficacy and safety of T-VEC + pembro in pts with advanced MEL who had progressive disease (PD) on prior anti–PD-1. Methods: This open-label, single-arm, multicenter, phase 2 study (NCT04068181) enrolled pts at 26 international sites (Jan 2020‒Feb 2021). Cohorts 1 and 2, primary and acquired resistance, respectively, received anti–PD-1 in a locally recurrent or metastatic setting and had PD within 12 wks of the last anti–PD-1 dose. Cohorts 3 and 4 included only pts who received adjuvant anti–PD-1 and were disease-free for < 6 mos (Cohort 3) or ≥ 6 mos (Cohort 4) before confirmed PD. Eligible pts had histologically confirmed unresectable or metastatic stage IIIB–IVM1d MEL, measurable and injectable disease, ECOG PS 0/1, and progressed on anti–PD-1 directly before enrollment. T-VEC at standard dosage and pembro 200 mg were given Q3W. The primary endpoint was objective response rate (ORR). Key secondary endpoints were complete response (CR) rate, progression-free survival (PFS), and safety. Tx decisions were per modified immune-related response criteria (irRECIST). Results: 72 pts (median age, 65 y) were enrolled. Of the 71 evaluable pts, 37 (52.1%) had stage IVM1b‒d disease, 30 (42.3%) had confirmed PD-L1–positive tumor (CPS ≥ 1%), 20 (28.2%) had a BRAFV600 mutation, and 21 (29.6%) had LDH > 1ULN. At data cutoff (Aug 2021), 47 (65.3%) pts remained on study. ORR was 0%, 6.7%, 40%, and 46.7% in cohorts 1–4, respectively (table). Any-grade Tx-related adverse events (TRAEs) were reported in 54 (76.1%) pts; the most common were pyrexia (29.6%), fatigue, and influenza-like illness (15.5% each). Grade ≥ 3 TRAEs occurred in 9 (12.7%) pts. Conclusions: T-VEC + pembro showed manageable safety in pts with advanced MEL after anti–PD-1 failure; the promising ORR observed in pts who progressed on prior adjuvant anti–PD-1 warrants further analysis. Clinical trial information: NCT04068181. [Table: see text]