Miracle-dz/UniFAR-FTUs huggingface dataset:
Updated results from a matching-adjusted indirect comparison of efficacy outcomes for ciltacabtagene autoleucel in CARTITUDE-1 versus idecabtagene vicleucel in KarMMa for the treatment of patients with relapsed or refractory multiple myeloma

Abstract Objective This study used the latest available data cuts from the CARTITUDE-1 and KarMMa clinical trials to update previously published matching-adjusted indirect treatment comparisons (MAICs) assessing the comparative efficacy of ciltacabtagene autoleucel (cilta-cel) versus the FDA-approved idecabtagene vicleucel (ide-cel) dose range of 300 to 450 × 106 CAR-positive T-cells in the treatment of patients with relapsed or refractory multiple myeloma (RRMM) who were previously treated with a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody (i.e. triple-class exposed). Methods MAICs were performed with the latest available individual patient data for cilta-cel (CARTITUDE-1) and published summary-level data for ide-cel (KarMMa). The analyses included treated patients from CARTITUDE-1 who satisfied the eligibility criteria for KarMMa. The MAIC adjusted for unbalanced baseline covariates of prognostic significance identified in the literature and by clinical expertise. Comparative efficacy was assessed for overall response rate (ORR), complete response or better (≥CR) rate, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Results Cilta-cel was associated with statistically significantly improved ORR (odds ratio [OR]: 94.93 [95% confidence interval [CI]: 21.86, 412.25; p < .0001]; relative risk [RR]: 1.34), ≥CR rate (OR: 5.65 [95% CI: 2.51, 12.69; p < .0001]; RR: 2.23), DoR (hazard ratio [HR]: 0.52 [95% CI: 0.30, 0.88; p = .0152]), PFS, (HR: 0.38 [95% CI: 0.24, 0.62; p < .0001]), and OS (HR: 0.43 [95% CI: 0.22, 0.88; p = .0200]) compared with ide-cel. Conclusions These analyses demonstrate improved efficacy with cilta-cel versus ide-cel for all outcomes over longer follow-up and highlight its therapeutic potential in triple-class exposed RRMM patients.
Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Importance The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic COVID-19 is unknown. Objective To evaluate the efficacy of ivermectin, 400 μg/kg, daily for 3 days compared with placebo for the treatment of early mild to moderate COVID-19. Design, Setting, and Participants ACTIV-6, an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19. A total of 1591 participants aged 30 years and older with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for 7 days or less, were enrolled from June 23, 2021, through February 4, 2022, with follow-up data through May 31, 2022, at 93 sites in the US. Interventions Participants were randomized to receive ivermectin, 400 μg/kg (n = 817), daily for 3 days or placebo (n = 774). Main Outcomes and Measures Time to sustained recovery, defined as at least 3 consecutive days without symptoms. There were 7 secondary outcomes, including a composite of hospitalization or death by day 28. Results Among 1800 participants who were randomized (mean [SD] age, 48 [12] years; 932 women [58.6%]; 753 [47.3%] reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1591 completed the trial. The hazard ratio (HR) for improvement in time to recovery was 1.07 (95% credible interval [CrI], 0.96-1.17; posterior P value [HR >1] = .91). The median time to recovery was 12 days (IQR, 11-13) in the ivermectin group and 13 days (IQR, 12-14) in the placebo group. There were 10 hospitalizations or deaths in the ivermectin group and 9 in the placebo group (1.2% vs 1.2%; HR, 1.1 [95% CrI, 0.4-2.6]). The most common serious adverse events were COVID-19 pneumonia (ivermectin [n = 5]; placebo [n = 7]) and venous thromboembolism (ivermectin [n = 1]; placebo [n = 5]). Conclusions and Relevance Among outpatients with mild to moderate COVID-19, treatment with ivermectin, compared with placebo, did not significantly improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. Trial Registration ClinicalTrials.gov Identifier: NCT04885530.
Evaluation of the Tocilizumab therapy in human cancers: Latest evidence and clinical potential

Tocilizumab (Actemra®), as the first human interleukin‐6 receptor (IL‐6R) antagonist, has been used in treating moderate to severe active rheumatoid arthritis (RA) patients who were undertreatment with one or more disease‐modifying anti‐rheumatic drugs (DMARDs) and did not improve significantly. Tocilizumab also has been administrated and confirmed in several inflammatory‐based diseases. Recently, tocilizumab has been prescribed to treat patients with advanced coronavirus disease (COVID‐19) and is used as one of the effective drugs in reducing the increased inflammation in these patients. On the other hand, cancer treatment has been considered by researchers one of the most important challenges to human health. Regarding inflammatory‐associated malignancies, it has been shown that inflammatory mediators such as interleukin‐1 beta (IL‐1β), IL‐6, and tumour necrosis factor‐alpha (TNF‐α) may play a role in tumorigenesis, thus targeting these cytokines as evidence suggested can be useful in the treatment of these types of cancers. This review summarized the role of the IL‐6/IL‐6R axis in inflammation‐based cancers and discussed the effectiveness and challenges of treating cancer with tocilizumab.
Frontal sinuses and human evolution

The frontal sinuses are cavities inside the frontal bone located at the junction between the face and the cranial vault and close to the brain. Despite a long history of study, understanding of their origin and variation through evolution is limited. This work compares most hominin species’ holotypes and other key individuals with extant hominids. It provides a unique and valuable perspective of the variation in sinuses position, shape, and dimensions based on a simple and reproducible methodology. We also observed a covariation between the size and shape of the sinuses and the underlying frontal lobes in hominin species from at least the appearance of Homo erectus. Our results additionally undermine hypotheses stating that hominin frontal sinuses were directly affected by biomechanical constraints resulting from either chewing or adaptation to climate. Last, we demonstrate their substantial potential for discussions of the evolutionary relationships between hominin species.
Generalized dark energy interactions with multiple fluids

In the search for an explanation for the current acceleration of the Universe, scalar fields are the most simple and useful tools to build models of dark energy. This field, however, must in principle couple with the rest of the world and not necessarily in the same way to different particles or fluids. We provide the most complete dynamical system analysis to date, consisting of a canonical scalar field conformally and disformally coupled to both dust and radiation. We perform a detailed study of the existence and stability conditions of the systems and comment on constraints imposed on the disformal coupling from Big-Bang Nucleosynthesis and given current limits on the variation of the fine-structure constant.
On the properties of compact groups identified in different photometric bands

Historically, compact group catalogues vary not only in their identification algorithms and selection functions, but also in their photometric bands. Differences between compact group catalogues have been reported. However, it is difficult to assess the impact of the photometric band in these differences given the variety of identification algorithms. We used the mock lightcone built by Henriques et al. (2012) to identify and compare compact groups in three different photometric bands: $K$, $r$, and $u$. We applied the same selection functions in the three bands, and found that compact groups in the u-band look the smallest in projection, the difference between the two brightest galaxies is the largest in the K-band, while compact groups in the r-band present the lowest compactness. We also investigated the differences between samples when galaxies are selected only in one particular band (pure compact groups) and those that exist regardless the band in which galaxies were observed (common compact groups). We found that the differences between the total samples are magnified, but also some others arise: pure-r compact groups are the largest in projection; pure-u compact groups have the brightest first ranked galaxies, and the most similar two first ranked galaxies; pure-K compact groups have the highest compactness and the most different two first ranked galaxies; and common compact groups show the largest percentage of physically dense groups. Therefore, without a careful selection and identification of the samples, the characteristic features of group properties in a particular photometric band could be overshadowed.
Law for the distance between successive earthquakes

[1] Discovery of a new law for the three-dimensional spatial distance between the foci of successive earthquakes is reported. Analyzing the seismic data taken between 1984 and 2001 in southern Californian, it is found that the cumulative distribution of the distances follows the modified Zipf-Mandelbrot law, showing complexity of geometry of the events.
Accessible Blockly: An Accessible Block-Based Programming Library for People with Visual Impairments

The visual and mouse-centric nature of block-based programming environments generally make them inaccessible and challenging to use by users with visual impairments who rely on assistive technologies to interact with computers. This prevents these users from participating in programming activities where these systems are used. This paper presents a prototype of an accessible block-based programming library called Accessible Blockly that allows users to create and navigate block-based code using a screen reader and a keyboard. This is an attempt to make the famous Blockly library accessible through a screen reader and keyboard. In this paper, we present the design and implementation of Accessible Blockly. We also discuss the evaluation of the library for block-based code navigation in a study with 12 blind programmers. Analysis of the study results shows that Accessible Blockly effectively aids users with reading and understanding block-based code. Participants found Accessible Blockly easy to use and less frustrating for navigating block-based programs. The participants also expressed enthusiasm and interest in using the keyboard and screen reader to navigate block-based code and in the accessibility of block-based programming.
A Collaborative Approach to Support Medication Management in Older Adults with Mild Cognitive Impairment Using Conversational Assistants (CAs)

Improving medication management for older adults with Mild Cognitive Impairment (MCI) requires designing systems that support functional independence and provide compensatory strategies as their abilities change. Traditional medication management interventions emphasize forming new habits alongside the traditional path of learning to use new technologies. In this study, we navigate designing for older adults with gradual cognitive decline by creating a conversational “check-in” system for routine medication management. We present the design of MATCHA - Medication Action To Check-In for Health Application, informed by exploratory focus groups and design sessions conducted with older adults with MCI and their caregivers, alongside our evaluation based on a two-phased deployment period of 20 weeks. Our results indicate that a conversational “check-in” medication management assistant increased system acceptance while also potentially decreasing the likelihood of accidental over-medication, a common concern for older adults dealing with MCI.
Mobile Phone Use by People with Mild to Moderate Dementia: Uncovering Challenges and Identifying Opportunities: Mobile Phone Use by People with Mild to Moderate Dementia

With the rising usage of mobile phones by people with mild dementia, and the documented barriers to technology use that exist for people with dementia, there is an open opportunity to study the specifics of mobile phone use by people with dementia. In this work we provide a first step towards filling this gap through an interview study with fourteen people with mild to moderate dementia. Our analysis yields insights into mobile phone use by people with mild to moderate dementia, challenges they experience with mobile phone use, and their ideas to address these challenges. Based on these findings, we discuss design opportunities to help achieve more accessible and supportive technology use for people with dementia. Our work opens up new opportunities for the design of systems focused on augmenting and enhancing the abilities of people with dementia.
Designing with and for People with Intellectual Disabilities

People with intellectual disabilities often experience inequalities that affect the standard of their everyday lives. Assistive technologies can help alleviate some of these inequalities, yet abandonment rates remain high. This is in part due to a lack of involvement of all stakeholders in their design and evaluation, thus resulting in outputs that do not meet this cohort’s complex and heterogeneous needs. The aim of this half-day workshop is to focus on community building in a field that is relatively thin and disjointed, thereby enabling researchers to share experiences on how to design for and with people with intellectual disabilities, provide internal support, and establish new collaborations. Workshop outcomes will help to fill a gap in the available guidelines on how to include people with intellectual disabilities in research, through more accessible protocols as well as personalised and better fit-for-purpose technologies.
Inter-rater Reliability of Command-Line Web Accessibility Evaluation Tools

This study compares four command-line interface (CLI) web accessibility tools, examining if one CLI tool is sufficient for automated accessibility evaluation. The four tools were: Axe-core/cli, IBM Equal Access NPM Accessibility Checker (Accessibility Checker), Pa11y-ci, and the A11y Machine. Inter-rater reliability was calculated using Gwet’s alpha coefficient 2 (AC2), and the results indicate very poor reliability between tools.
State of the Art in AAC: A Systematic Review and Taxonomy

People with complex communication needs (CCNs) can use high-tech augmentative and alternative communication (AAC) devices and systems to compensate for communication difficulties. While many use AAC effectively, much research has highlighted challenges – for instance, high rates of abandonment and solutions which are not appropriate for their end-users. Presently, we lack a detailed survey of this field to comprehend these shortcomings and understand how the accessibility community might direct its efforts to design more effective AAC. In response to this, we conduct a systematic review and taxonomy of high-tech AAC devices and interventions, reporting results from 562 articles identified in the ACM DL and SCOPUS databases. We provide a taxonomical overview of the current state of AAC devices – e.g. their interaction modalities and characteristics. We describe the communities of focus explored, and the methodological approaches used. We contrast findings in the broader accessibility and HCI literature to delineate future avenues for exploration in light of the current taxonomy, offer a reassessment of the norms and incumbent research methodologies and present a discourse on the communities of focus for AAC and interventions.
A $\mathcal {M}\gtrsim 3$ shock in ‘El Gordo’ cluster and the origin of the radio relic

We present an X-ray and radio study of the famous `El Gordo', a massive and distant ($z=0.87$) galaxy cluster. In the deep (340 ks) Chandra observation, the cluster appears with an elongated and cometary morphology, a sign of its current merging state. The GMRT radio observations at 610 MHz reveal the presence of a radio halo which remarkably overlaps the X-ray cluster emission and connects a couple of radio relics. We detect a strong shock ($\mathcal{M}\gtrsim3$) in the NW periphery of the cluster, co-spatially located with the radio relic. This is the most distant ($z=0.87$) and one of the strongest shock detected in a galaxy cluster. This work supports the relic-shock connection and allows to investigate the origin of these radio sources in a uncommon regime of $\mathcal{M}\gtrsim3$. For this particular case we found that shock acceleration from the thermal pool is still a viable possibility.
What drives people’s protective behaviors during the early stage of the COVID-19 pandemic in China

This study systematically examined people’s protective behaviors against COVID-19 in China, and particular attention was given to people’s perceived threat and information-processing strategies. This study constructed a conceptual model and used structural equation modeling to explore this issue, and a questionnaire survey was conducted to collect data involving 4,605 participants during the early stage of the COVID-19 pandemic in China. The results showed that people’s initial information acquisition played an essential role in their behavioral responses; acquiring more initial information about COVID-19 would make them perceive a higher threat and present a higher demand for information, then making them more likely to seek and process information, and subsequently motivating their protective behaviors. In addition to increasing people’s information needs, the perceived threat could also strengthen the analytical assessment and affect protective behavior positively but failed to predict the experiential assessment. Driven by information need, information seeking significantly influenced protective behavior; it also facilitated analytical assessment and decreased experiential assessment, thus predicting people’s protective behaviors. Protective behaviors were spurred by analytical assessment but negatively influenced by the experiential assessment.
CONSEQUENCES OF DYNAMICAL DISRUPTION AND MASS SEGREGATION FOR THE BINARY FREQUENCIES OF STAR CLUSTERS

The massive (13,000–26,000 M☉) and young (15–30 Myr) Large Magellanic Cloud star cluster NGC 1818 reveals an unexpected increasing binary frequency with radius for F-type stars (1.3–2.2 M☉). This is in contrast to many older star clusters that show a decreasing binary frequency with radius. We study this phenomenon with sophisticated N-body modeling, exploring a range of initial conditions, from smooth virialized density distributions to highly substructured and collapsing configurations. We find that many of these models can reproduce the cluster's observed properties, although with a modest preference for substructured initial conditions. Our models produce the observed radial trend in binary frequency through disruption of soft binaries (with semi-major axes, a ≳ 3000 AU), on approximately a crossing time (∼5.4 Myr), preferentially in the cluster core. Mass segregation subsequently causes the binaries to sink toward the core. After roughly one initial half-mass relaxation time (trh(0) ∼ 340 Myr) the radial binary frequency distribution becomes bimodal, the innermost binaries having already segregated toward the core, leaving a minimum in the radial binary frequency distribution that marches outward with time. After 4–6 trh(0), the rising distribution in the halo disappears, leaving a radial distribution that rises only toward the core. Thus, both a radial binary frequency distribution that falls toward the core (as observed for NGC 1818) and one that rises toward the core (as for older star clusters) can arise naturally from the same evolutionary sequence owing to binary disruption and mass segregation in rich star clusters.
Open Research Online Into the Macroscope: Systematic integration of micro-and macro-scale study of digital reading

: The emergence of digital reading platforms is opening up new avenues for the empirical study of how readers interact with literature. Such study of digital reading requires a deep structured and explicit integration of micro- and macro-scale research methodologies. In our vision, empirical studies are of critical importance to address Humanities questions, but they must be reconciled within the scope of the Humanities. In this scenario, we propose a vision and framework for DH as a structural integration of both empirical studies on reading and Humanities studies (such as reception studies and book history). A case study based on webcomics will also be included as an example.
Testing the origin of ~3.55 keV line in individual galaxy clusters observed with XMM-Newton

If the unidentified emission line at ~3.55 keV previously found in spectra of nearby galaxies and galaxy clusters is due to radiatively decaying dark matter, one should detect the signal of comparable strength from many cosmic objects of different nature. By studying existing dark matter distributions in galaxy clusters we identified top-19 of them observed by XMM-Newton X-ray cosmic mission, and analyzed the data for the presence of the new line. In 8 of them, we identified > 2 sigma positive line-like residuals with average position 3.52 +/- 0.08 keV in the emitter's frame. Their observed properties are unlikely to be explained by statistical fluctuations or astrophysical emission lines; observed line position in M31 and Galactic Center makes an additional argument against general-type systematics. Being interpreted as decaying dark matter line, the new detections correspond to radiative decay lifetime tau_dm ~ (3.5-6) x 10^27 s consistent with previous detections.
Detecting the 21 cm forest in the 21 cm power spectrum

We describe a new technique for constraining the radio loud population of active galactic nuclei at high redshift by measuring the imprint of 21 cm spectral absorption features (the 21 cm forest) on the 21 cm power spectrum. Using semi-numerical simulations of the intergalactic medium and a semi-empirical source population we show that the 21 cm forest dominates a distinctive region of $k$-space, $k \gtrsim 0.5 \text{Mpc}^{-1}$. By simulating foregrounds and noise for current and potential radio arrays, we find that a next generation instrument with a collecting area on the order of $\sim 0.1\text{km}^2$ (such as the Hydrogen Epoch of Reionization Array) may separately constrain the X-ray heating history at large spatial scales and radio loud active galactic nuclei of the model we study at small ones. We extrapolate our detectability predictions for a single radio loud active galactic nuclei population to arbitrary source scenarios by analytically relating the 21 cm forest power spectrum to the optical depth power spectrum and an integral over the radio luminosity function.