Miracle-dz/UniFAR-FTUs huggingface dataset:
Socioeconomic predictors of case presentations and outcomes in 225 nonfunctional pituitary adenoma resections.

OBJECTIVE Clinical presentations and outcomes of nonfunctional pituitary adenoma (NFPA) resections can vary widely, and very little prior research has analyzed this variance through a socioeconomic lens. This study sought to determine whether socioeconomic status (SES) influences NFPA presentations and postoperative outcomes, as these associations could aid physicians in understanding case prognoses and complications. METHODS The authors retrospectively analyzed 225 NFPA resections from 2012 to 2019 at their institution. Race, ethnicity, insurance status, estimated income, and having a primary care provider (PCP) were collected as 5 markers of SES. These markers were correlated with presenting tumor burden, presenting symptoms, surgical outcomes, and long-term clinical outcomes. RESULTS All 5 examined SES markers influenced variance in patient presentation or outcome. Insurance status's effects on patient presentations disappeared when examining only patients with PCPs. Having a PCP was associated with significantly smaller tumor size at diagnosis (effect size = 0.404, p < 0.0001). After surgery, patients with PCPs had shorter postoperative hospital lengths of stay (p = 0.043) and lower rates of readmission within 30 days of discharge (OR 0.256, p = 0.047). Despite continuing follow-up for longer durations (p = 0.0004), patients with PCPs also had lower rates of tumor recurrence (p < 0.0001). Higher estimated income was similarly associated with longer follow-up (p = 0.002) and lower rates of tumor recurrence (p = 0.013). Among patients with PCPs, income was not associated with recurrence. CONCLUSIONS This study found that while all 5 variables (race, ethnicity, insurance, PCP status, and estimated income) affected NFPA presentations and outcomes, having a PCP was the single most important of these socioeconomic factors, impacting hospital lengths of stay, readmission rates, follow-up adherence, and tumor recurrence. Having a PCP even protected low-income patients from experiencing increased rates of tumor recurrence. These protective findings suggest that addressing socioeconomic disparities may lead to better NFPA presentations and outcomes.
Enhancing the use of EHR systems for pragmatic embedded research: lessons from the NIH Health Care Systems Research Collaboratory

Abstract Objective We identified challenges and solutions to using electronic health record (EHR) systems for the design and conduct of pragmatic research. Materials and Methods Since 2012, the Health Care Systems Research Collaboratory has served as the resource coordinating center for 21 pragmatic clinical trial demonstration projects. The EHR Core working group invited these demonstration projects to complete a written semistructured survey and used an inductive approach to review responses and identify EHR-related challenges and suggested EHR enhancements. Results We received survey responses from 20 projects and identified 21 challenges that fell into 6 broad themes: (1) inadequate collection of patient-reported outcome data, (2) lack of structured data collection, (3) data standardization, (4) resources to support customization of EHRs, (5) difficulties aggregating data across sites, and (6) accessing EHR data. Discussion Based on these findings, we formulated 6 prerequisites for PCTs that would enable the conduct of pragmatic research: (1) integrate the collection of patient-centered data into EHR systems, (2) facilitate structured research data collection by leveraging standard EHR functions, usable interfaces, and standard workflows, (3) support the creation of high-quality research data by using standards, (4) ensure adequate IT staff to support embedded research, (5) create aggregate, multidata type resources for multisite trials, and (6) create re-usable and automated queries. Conclusion We are hopeful our collection of specific EHR challenges and research needs will drive health system leaders, policymakers, and EHR designers to support these suggestions to improve our national capacity for generating real-world evidence.
Characteristics of Growth in Children With Classic Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency During Adrenarche and Beyond

Abstract Context Patients with classic congenital adrenal hyperplasia (CAH) often do not achieve their full growth potential. Adrenarche may accelerate bone maturation and thereby result in decreased growth in CAH. Objective The study aimed to analyze the impact of growth during adrenarche on final height of adequately treated classic CAH patients. Methods This retrospective, multicenter study (4 academic pediatric endocrinology centers) included 41 patients with classical CAH, born 1990-2012. We assessed skeletal maturation (bone age), growth velocity, and (projected) adult height outcomes, and analyzed potential influencing factors, such as sex, genotype, and glucocorticoid therapy. Results Patients with classic CAH were shorter than peers (−0.4 SDS ± 0.8 SD) and their parents (corrected final height −0.6 SDS ± 1.0 SD). Analysis of growth during adrenarche revealed 2 different growth patterns: patients with accelerating bone age (49%), and patients with nonaccelerating bone age relative to chronological age (BA-CA). Patients with accelerating BA-CA were taller than the normal population during adrenarche years (P = 0.001) and were predicted to achieve lower adult height SDS (−0.9 SDS [95% CI, −1.3; −0.5]) than nonaccelerating patients when assessed during adrenarche (0.2 SDS [95% CI, −0.3; 0.8]). Final adult height was similarly reduced in both accelerating and nonaccelerating BA-CA groups (−0.4 SDS [95% CI, −0.9; 0.1] vs −0.3 SDS [95% CI, [−0.8; 0.1]). Conclusion Patients with and without significant bone age advancement, and thus differing height prediction during adrenarche, showed similar (predicted) final height when reassessed during pubertal years. Bone age alone should not be used during adrenarche as clinical marker for metabolic control in CAH treatment.
Synaptotagmin‐11 inhibits spontaneous neurotransmission through vti1a

Recent work has revealed that spontaneous release plays critical roles in the central nervous system, but how it is regulated remains elusive. Here, we report that synaptotagmin‐11 (Syt11), a Ca2+‐independent Syt isoform associated with schizophrenia and Parkinson's disease, suppressed spontaneous release. Syt11‐knockout hippocampal neurons showed an increased frequency of miniature excitatory post‐synaptic currents while over‐expression of Syt11 inversely decreased the frequency. Neither knockout nor over‐expression of Syt11 affected the average amplitude, suggesting the pre‐synaptic regulation of spontaneous neurotransmission by Syt11. Glutathione S‐transferase pull‐down, co‐immunoprecipitation, and affinity‐purification experiments demonstrated a direct interaction of Syt11 with vps10p‐tail‐interactor‐1a (vti1a), a non‐canonical SNARE protein that maintains spontaneous release. Importantly, knockdown of vti1a reversed the phenotype of Syt11 knockout, identifying vti1a as the main target of Syt11 inhibition. Domain analysis revealed that the C2A domain of Syt11 bound vti1a with high affinity. Consistently, expression of the C2A domain alone rescued the phenotype of elevated spontaneous release in Syt11‐knockout neurons similar to the full‐length protein. Altogether, our results suggest that Syt11 inhibits vti1a‐containing vesicles during spontaneous release.
Early flowering, good grain quality mutants through gamma rays and EMS for enhancing per day productivity in rice (Oryza sativa L.)

Abstract Purpose Rice is the prominent crop of world and it frames the important component of food chain. But, long duration of highly preferred rice varieties requires more water and are prone to biotic and abiotic stresses. Short duration rice varieties serve as a promising alternative in such cases. Hence, the present study was taken up to induce early flowering mutants in popular rice variety Bapatla 2231 (BPT 2231), a long duration medium slender rice variety using gamma rays and Ethyl Methane Sulfonate (EMS) treatment combinations. Materials and methods Five hundred well filled and viable grains of optimum moisture content (12%) were subjected to irradiation with 8 doses comprising 100 Gy, 200 Gy, 300 Gy, 350 Gy, 400 Gy, 450 Gy, 500 Gy and 600 Gy treatments. For combination treatments, the irradiated seeds of gamma rays were further treated with 30 mM concentrations of Ethyl Methane sulfonate (EMS). The irradiated population were raised up to M3 generation for the identification of early maturing mutants. The isolated early maturing mutants in M3 generation were characterized for phenotypic, biochemical and grain qualities. Results The frequency of desirable early maturing mutants was observed more in combination treatments than the individual treatments of gamma rays. A total of 34 early maturing mutants (M) with variation for grain quality and biochemical traits were obtained. The mutants M-1, M-3, M-5, M-32, and M-34 were high yielding with fine grain type. The mutants M-4, M-17, M-18, M-19, M-20, and M-26 were high yielding with bold grain type. The mutants M-22, M-23, M-24, M-27, and M-28 were high in nutrient content. The early mutants matured 40−50 days earlier than control. Conclusion In this variety, the combination treatments showed higher mutation frequency, mutagenic effectiveness and efficiency than the gamma rays in induction of both chlorophyll and viable mutants. This study revealed that the combination treatments were more effective in inducing early mutants than the gamma ray treatments alone. The early maturing mutants can be released as variety after evaluation under different yield trials and the mutants with increased nutrient content and varied grain quality can be utilized in hybridization/heterosis breeding programs for rice crop improvement.
MRI‐Visible siRNA Nanomedicine Directing Neuronal Differentiation of Neural Stem Cells in Stroke

A major challenge in stroke treatment is the restoration of neural circuit in which neuron function plays a central role. Although transplantation of exogenous neural stem cells (NSCs) is admittedly a promising therapeutical means, the treatment outcome is greatly affected due to the poor NSCs differentiation into neurons caused by myelin associated inhibitory factors binding to Nogo‐66 receptor (NgR). Herein, a nanoscale polymersome is developed to codeliver superparamagnetic iron oxide nanoparticles and siRNA targeting NgR gene (siNgR) into NSCs. This multifunctional nanomedicine directs neuronal differentiation of NSCs through silencing the NgR gene and meanwhile allows a noninvasive monitoring of NSC migration with magnetic resonance imaging. An improved recovery of neural function is achieved in rat ischemic stroke model. The results demonstrate the great potential of the multifunctional siRNA nanomedicine in stroke treatment based on stem cell transplantation.
First-in-Class Anti-immunoglobulin–like Transcript 4 Myeloid-Specific Antibody MK-4830 Abrogates a PD-1 Resistance Mechanism in Patients with Advanced Solid Tumors

Purpose: In this first-in-human study (NCT03564691) in advanced solid tumors, we investigated a novel first-in-class human IgG4 monoclonal antibody targeting the immunoglobulin-like transcript 4 (ILT4) receptor, MK-4830, as monotherapy and in combination with pembrolizumab. Patients and Methods: Patients with histologically/cytologically confirmed advanced solid tumors, measurable disease by RECIST v1.1, and evaluable baseline tumor sample received escalating doses of intravenous MK-4830 every 3 weeks as monotherapy (parts A and B) and in combination with pembrolizumab (part C). Safety and tolerability were the primary objectives. Pharmacokinetics, objective response rate per RECIST v1.1, and molecular biomarkers were also evaluated. Results: Of 84 patients, 50 received monotherapy and 34 received combination therapy. No dose-limiting toxicities were observed; maximum tolerated dose was not reached. MK-4830 showed dose-related target engagement. Eleven of 34 patients in the dose-escalation phase who received combination therapy achieved objective responses; 5 previously had progressive disease on anti–PD-1/PD-L1 therapies. Exploratory evaluation of the association between response and pretreatment gene expression related to interferon-gamma signaling in tumors suggested higher sensitivity to T-cell inflammation with combination therapy than historically expected with pembrolizumab monotherapy, with greater response at more moderate levels of inflammation. Conclusions: This first-in-class MK-4830 antibody dosed as monotherapy and in combination with pembrolizumab was well tolerated with no unexpected toxicities, and demonstrated dose-related evidence of target engagement and antitumor activity. Inflammation intrinsic to the ILT4 mechanism may be facilitated by alleviating the myeloid-suppressive components of the tumor microenvironment, supporting the target of ILT4 as a potential novel immunotherapy in combination with an anti–PD-1/PD-L1 agent.
Proteomics of colorectal cancer liver metastasis: A quantitative focus on drug elimination and pharmacodynamics effects

This study aims to quantify drug‐metabolising enzymes, transporters, receptor tyrosine kinases (RTKs) and protein markers (involved in pathways affected in cancer) in pooled healthy, histologically normal and matched cancerous liver microsomes from colorectal cancer liver metastasis (CRLM) patients.
High-reliability, high-melting, lead-free, mixed solder paste System-BiAgXⓇ.

BiAgX®, a mixed solder powder paste composed of a primary high-melting solder powder and an additive low-melting solder powder, exhibited a melting temperature above 260 °C and was comparable to, or even better than, the reliability of high-lead solders. The additive solder is designed to react preferentially with various surface metallizations and form a controllable intermetallic layer. Inside the joints, sub-micron AgSn particles are dispersed surrounding Bi colonies, which constrain the dislocation movement, thus enhancing strength, ductility, and associated joint reliability.
Perfusion Strategies for Neonatal Aortic Arch Surgery—Comparing AKI Risk: Apples and Apples? Or Apples and Oranges?

Perfusion Strategies for Neonatal Aortic Arch Surgery—Comparing AKI Risk: Apples and Apples? Or Apples and Oranges? Emily Downs, MD, Benjamin Oslen, MD, and Katja M. Gist DO, MSc 1 Department of Surgery, School of Medicine, Children’s Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, CO, USA 2 Department of Graduate Medical Education, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA 3 Department of Pediatrics, School of Medicine, Children’s Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Reactive oxygen and hydrogen species generation in radio-frequency atmospheric pressure plasmas - Experimental and numerical investigations

Atmospheric pressure plasmas (APPs) are known to be effective sources for reactive oxygen and nitrogen species (RS), making them potentially suitable for applications in biomedicine, where these species are believed to play a crucial role. However, in order to fully establish plasma sources in biomedicine, detailed characterisation of the RS produced is required. This is particularly challenging at atmospheric pressure, because of high collision rates among particles leading to fast de-excitation of excited states (quenching), complex gas mixing, and the small physical dimensions of the investigated systems, which effectively limits the accurate application of several commonly used diagnostic techniques applicable in low pressure systems. The motivation of this work is therefore to investigate the chemical kinetics in APPs, using a combination of simulations and experimental diagnostics, which are able to overcome the above-mentioned challenges. Experimentally, absolute RS species densities such as O, OH, H2O2, N, and NO, are determined using absorption spectroscopy in the UV and VUV spectral range, a technique independent on quenching and providing high spectral resolution. Spatially resolved two-photon absorption laser-induced fluorescence with sub-nanosecond temporal resolution enables the determination of atomic species densities (O and H) in the plasma effluent. Experimental values are benchmarked against zero-dimensional plasma-chemical kinetics simulations, which are used to investigate the principal reaction mechanisms leading to the formation and consumption of the investigated species. It is generally found that formation pathways depend strongly on the concentration of molecules in the feed gas, and the position in the plasma jet, as well as potential impurities being present in the feed gas, which is an important aspect for consideration for the applications of APPs. The results are used to propose possible tailoring schemes to optimise RS productions in APPs.
Predicting $GME Stock Price Movement Using Sentiment from Reddit r/wallstreetbets

In early 2021, GameStop’s (NYSE: GME) stock underwent a prolonged period of rapid, drastic ﬂuc-tuations in price resulting from a short squeeze orchestrated by the r/wallstreetbets community on Reddit. In this paper, we present our experiments and ﬁndings for predicting the direction of GME’s daily price movement using sentiment from r/wallstreetbets posts. We use VADER for automatic sentiment analysis combined with word2vec and BERT semantic representations, and experiment with a variety of classiﬁer models, including both traditional ML and deep learning approaches.
Generating Justifications in a Spatial Question-Answering Dialogue System for a Blocks World

As AI reaches wider adoption, designing systems that are explainable and interpretable becomes a critical necessity. In particular, when it comes to dialogue systems, their reasoning must be transparent and must comply with human intuitions in order for them to be integrated seamlessly into day-to-day collaborative human-machine activities. Here, we describe our ongoing work on a (general purpose) dialogue system equipped with a spatial specialist with explanatory capabilities. We applied this system to a particular task of characterizing spatial configurations of blocks in a simple physical Blocks World (BW) domain using natural locative expressions, as well as generating justifications for the proposed spatial descriptions by indicating the factors that the system used to arrive at a particular conclusion.
Incremental Graph-Based Semantics and Reasoning for Conversational AI

The next generation of conversational AI systems need to: (1) process language incrementally, token-by-token to be more responsive and enable handling of conversational phenomena such as pauses, restarts and self-corrections; (2) reason incrementally allowing meaning to be established beyond what is said; (3) be transparent and controllable, allowing designers as well as the system itself to easily establish reasons for particular behaviour and tailor to particular user groups, or domains. In this short paper we present ongoing preliminary work combining Dynamic Syntax (DS) - an incremental, semantic grammar framework - with the Resource Description Framework (RDF). This paves the way for the creation of incremental semantic parsers that progressively output semantic RDF graphs as an utterance unfolds in real-time. We also outline how the parser can be integrated with an incremental reasoning engine through RDF. We argue that this DS-RDF hybrid satisfies the desiderata listed above, yielding semantic infrastructure that can be used to build responsive, real-time, interpretable Conversational AI that can be rapidly customised for specific user groups such as people with dementia.
Gesture Generation

Gestures accompany our speech in ways that punctuate, augment, substitute for, and even contradict verbal information. Such co-speech gestures draw listeners’ attention to specific phrases, indicate the speaker’s feelings toward a subject, or even convey “off-the-record” information that is excluded from our spoken words. The study of co-speech gesture stretches at least as far back as the work of Quin­ tilian in 50 AD, and draws from the disciplines of cognitive science, performance
Introduction to Socially Interactive Agents

and information that can be read or watched in separate windows. The research discipline of human–computer interaction (HCI) is constantly develop­ ing new and creative systems that go beyond this traditional interaction for a more intuitive usage, for example, with technology such as touch interaction, virtual reality, tangible computing, and many more. Taking a different approach to realize natural and intuitive interaction, the research area of socially interactive agents (SIAs) aims to develop artificial agents that can interact via communication channels that come more natural to human interactants by equipping the interface with a body that interacts multi-modally by using verbal, para-verbal, and non-verbal behaviors. With it, communication styles that are known from human face-to-face interaction can be transferred to interaction with machines. SIAs (see Figure 1.1 for examples) have been developed under different names in different research fields such as intelligent virtual agents (IVAs), embodied con­ versational agents (ECAs), or social robotics (SRs) (see below for definitions of the respective terms). More than 20 years of research and development in these fields have drastically advanced the state of the art. For this book, we chose to use the term socially interactive agents (or SIAs) as it includes both physical and virtual embodiments, while highlighting their ability for social interaction as well as the need to realize socially intelligent, autonomous behaviors. We define SIAs as follows:
Teaching at Belfast and Oxford

Although as a youth he had been known as ‘the Professor’ by his younger siblings, Tony Hoare’s first academic appointment was in 1968, as Professor and Head of the Department of Computer Science at Queen’s University Belfast. His second was in 1977 as Professor of Computation and Head of the Programming Research Group of the Computing Laboratory at the University of Oxford — until 2011 the closest thing that the University had to a Department of Computer Science.