Miracle-dz/UniFAR-FTUs huggingface dataset:
Maralixibat for the treatment of PFIC: Long‐term, IBAT inhibition in an open‐label, Phase 2 study

Children with progressive familial intrahepatic cholestasis, including bile salt export pump (BSEP) and familial intrahepatic cholestasis–associated protein 1 (FIC1) deficiencies, suffer debilitating cholestatic pruritus that adversely affects growth and quality of life (QoL). Reliance on surgical interventions, including liver transplantation, highlights the unmet therapeutic need. INDIGO was an open‐label, Phase 2, international, long‐term study to assess the efficacy and safety of maralixibat in children with FIC1 or BSEP deficiencies. Thirty‐three patients, ranging from 12 months to 18 years of age, were enrolled. Eight had FIC1 deficiency and 25 had BSEP deficiency. Of the latter, 6 had biallelic, protein truncating mutations (t)‐BSEP, and 19 had ≥ 1 nontruncating mutation (nt)‐BSEP. Patients received maralixibat 266 μg/kg orally, once daily, from baseline to Week 72, with twice‐daily dosing permitted from Week 72. Long‐term efficacy was determined at Week 240. Serum bile acid (sBA) response (reduction in sBAs of > 75% from baseline or concentrations <102.0 μmol/L) was achieved in 7 patients with nt‐BSEP, 6 during once‐daily dosing, and 1 after switching to twice‐daily dosing. sBA responders also demonstrated marked reductions in sBAs and pruritus, and increases in height, weight, and QoL. All sBA responders remained liver transplant–free after > 5 years. No patients with FIC1 deficiency or t‐BSEP deficiency met the sBA responder criteria during the study. Maralixibat was generally well‐tolerated throughout the study. Conclusion: Response to maralixibat was dependent on progressive familial intrahepatic cholestasis subtype, and 6 of 19 patients with nt‐BSEP experienced rapid and sustained reductions in sBA levels. The 7 responders survived with native liver and experienced clinically significant reductions in pruritus and meaningful improvements in growth and QoL. Maralixibat may represent a well‐tolerated alternative to surgical intervention.
Genomic Features of Lung-Recurrent Hormone-Sensitive Prostate Cancer

PURPOSE Pulmonary involvement is rare in metastatic hormone-sensitive prostate cancer (mHSPC) that recurs after treatment for localized disease. Guidelines recommend intensive systemic therapy, similar to patients with liver metastases, but some lung-recurrent mHSPC may have good outcomes. Genomic features of lung metastases may clarify disease aggression, but are poorly understood since lung biopsy is rarely performed. We present a comparative assessment of genomic drivers and heterogeneity in metachronous prostate tumors and lung metastases. METHODS We leveraged a prospective functional imaging study of 208 biochemically recurrent prostate cancers to identify 10 patients with lung-recurrent mHSPC. Histologic diagnosis was attained via thoracic surgery or fine-needle lung biopsy. We retrieved clinical data and performed multiregion sampling of primary tumors and metastases. Targeted and/or whole-exome sequencing was applied to 46 primary and 32 metastatic foci. RESULTS Unusually for mHSPC, all patients remained alive despite a median follow-up of 11.5 years. Several patients experienced long-term freedom from systemic treatment. The genomic landscape of lung-recurrent mHSPC was typical of curable prostate cancer with frequent PTEN, SPOP, and chromosome 8p alterations, and there were no deleterious TP53 and DNA damage repair gene mutations that characterize aggressive prostate cancer. Despite a long median time to recurrence (76.8 months), copy number alterations and clonal mutations were highly conserved between metastatic and primary foci, consistent with intrapatient homogeneity and limited genomic evolution. CONCLUSION In this retrospective hypothesis-generating study, we observed indolent genomic etiology in selected lung-recurrent mHSPC, cautioning against grouping these patients together with liver or bone-predominant mHSPC. Although our data do not generalize to all patients with lung metastases, the results encourage prospective efforts to stratify lung-recurrent mHSPC by genomic features. Fonseca, Van der Eecken, and Herberts et al show that some lung-recurrent #ProstateCancer is defined by clinical and genomic indolence
Effects of a Short-Term Heat Acclimation Protocol in Elite Amateur Boxers

Abstract Stone, BL, Ashley, JD, Skinner, RM, Polanco, JP, Walters, MT, Schilling, BK, and Kellawan, JM. Effects of a short-term heat acclimation protocol in elite amateur boxers. J Strength Cond Res 36(7): 1966–1971, 2022—Boxing requires proficient technical and tactical skills coupled with high levels of physiological capacity. Although heat and humidity negatively affect acute exercise performance, short-term exercise training in hot and humid environments can lead to physiological adaptations that enhance exercise performance in both hot and thermoneutral conditions. In highly trained endurance athletes, exercise-induced acclimation can occur in as little as 5 days (known as short-term heat acclimation [STHA]). However, the impact of a 5-day heat acclimation (5-DayHA) in combat athletes, such as elite amateur boxers, is unknown. The aim of the present investigation was to determine whether a 5-DayHA improves aerobic performance in a thermoneutral environment and causes positive physiological adaptations in elite boxers. Seven elite amateur boxers underwent a 5-DayHA protocol, consisting of 60-minute exercise sessions in an environmental chamber at 32 °C and 70% relative humidity. Repeat sprint test (RST) evaluated aerobic performance in a thermoneutral environment 24 hours before and after the 5-DayHA. Presession and postsession hydration status (urine specific gravity) and body mass were assessed. After a 5-DayHA period, boxers significantly improved RST performance (13 ± 7 to 19 ± 7 sprints, d = 0.92, p = 0.03) but not pre-exercise hydration status (1.02 ± 0.01 to 1.01 ± 0.01, d = 0.82, p = 0.07). Therefore, these findings suggest 5-DayHA enhances aerobic performance in elite-level amateur boxers and may provide a viable training option for elite combat athletes.
A Water-Free Omega-3 Fatty Acid Eye Drop Formulation for the Treatment of Evaporative Dry Eye Disease: A Prospective, Multicenter Noninterventional Study

Purpose: NovaTears®+Omega-3 is a water-free eye drop solution with non-animal-derived omega-3 fatty acids. It allows to supplement omega-3 fatty acids directly in the tear film of patients with dry eye disease (DED). This post-market clinical follow-up (PMCF) study evaluated for the first time the effects on clinical signs and patient symptoms of DED, and safety and tolerability of NovaTears+Omega-3 (0.2%) eye drops, when used in accordance with its approved label. Methods: A prospective, multicenter, single-arm, uncontrolled, open-label observational cohort study was performed in patients suffering from symptoms of evaporative DED. Patients were treated 4 times daily bilaterally according to the instructions for use for 8 weeks, and standard of care clinical end points were assessed at baseline and follow-up. The trial was conducted at 2 investigational sites in Germany, Europe. Results: Thirty-six patients were included and 33 completed the study. NovaTears+Omega-3 (0.2%) showed clinically and statistically significant improvements in various clinical signs, such as total corneal staining, tear film break-up time, and Meibomian gland dysfunction (MGD) score, as well as in symptoms measured by Ocular Surface Disease Index (OSDI©) and visual analog scales over the 8-week treatment period with change from baseline P values all <0.0001. No worsening of any safety parameter (intraocular pressure, slit-lamp examination, visual acuity) was observed, and no adverse event was reported throughout the study. Conclusions: In this observational PMCF study, NovaTears+Omega-3 was safe and well tolerated. Treatment over an 8-week period resulted in significantly improved clinical signs and subjective symptoms in patients with evaporative dry eye. The study was registered at www.clinicaltrials. gov (NCT04521465).
Impact of illicit opioid use on markers of monocyte activation and systemic inflammation in people living with HIV

Introduction We hypothesize that illicit opioid use increases bacterial translocation from the gut, which intensifies systemic inflammation. Objective To investigate the association between opioid use and plasma soluble CD14 [sCD14], interleukin-6 [IL-6] and D-dimer in people living with HIV (PLWH). Methods We analyzed data from the Russia ARCH study–an observational cohort of 351 ART-naive PLWH in St. Petersburg, Russia. Plasma levels of sCD14 (primary outcome), IL-6 and D-dimer (secondary outcomes) were evaluated at baseline, 12, and 24 months. Participants were categorized into three groups based on illicit opioid use: current, prior, and never opioid use. Linear mixed effects models were used to evaluate associations. Results Compared to never opioid use, sCD14 levels were significantly higher for participants with current opioid use (AMD = 197.8 ng/ml [11.4, 384.2], p = 0.04). IL-6 levels were also higher for participants with current vs. never opioid use (ARM = 2.10 [1.56, 2.83], p <0.001). D-dimer levels were higher for current (ARM = 1.95 [1.43, 2.64], p <0.001) and prior (ARM = 1.57 [1.17, 2.09], p = 0.004) compared to never opioid use. Conclusions Among PLWH, current opioid use compared to never use is associated with increased monocyte activation and systemic inflammation.
Reinforcement learning for systems pharmacology-oriented and personalized drug design

ABSTRACT Introduction Many multi-genic systemic diseases such as neurological disorders, inflammatory diseases, and the majority of cancers do not have effective treatments yet. Reinforcement learning powered systems pharmacology is a potentially effective approach to designing personalized therapies for untreatable complex diseases. Areas covered In this survey, state-of-the-art reinforcement learning methods and their latest applications to drug design are reviewed. The challenges on harnessing reinforcement learning for systems pharmacology and personalized medicine are discussed. Potential solutions to overcome the challenges are proposed. Expert opinion In spite of successful application of advanced reinforcement learning techniques to target-based drug discovery, new reinforcement learning strategies are needed to address systems pharmacology-oriented personalized de novo drug design.
A novel standby mode detection scheme with light load efficiency improvement

A novel standby mode scheme with light load efficiency improvement is proposed in this paper, which is especially suitable for modern boost dc-dc converters powered by Li-ion battery. The proposed output load estimator is able to accurately reflect the output load current under light load condition once inductor current enters in the discontinuous conduction mode (DCM). Our experimental results show that the proposed boost dc-dc converter can automatically select approximate PWM switching frequency according to the detected information of the proposed output load estimator, regardless of power supply and inductor value.
Standards and Initiatives for Service Modeling - The Case of OMG SoaML

Service modeling is a key element of any service-oriented system. It is the foundation on which core service-related tasks such as service discovery, composition, and mediation rely. During the past years standardization bodies such as W3C, OMG and OASIS have been working on standardizing various aspects of services such as service functionalities, behavior, quality of services, etc. At the same time, initiatives from academia focused on developing ontologies and formal languages for specifying services. In this paper we give a brief overview of relevant initiatives and standardization activities in the area of service modeling, and, as an example of the use of such standards, guide the reader through the use of the OMG Service oriented architecture Modeling Language (SoaML) in a concrete service-oriented scenario in the manufacturing domain.
De adoptie van digitale leermiddelen door leraren in het Nederlandse basisonderwijs

De hedendaagse maatschappij vertoont een toename in het gebruik van digitale media waardoor digitale kennis en vaardigheden steeds belangrijker worden. Het is daarom van belang dat kinderen op een jonge leeftijd kennis maken met nieuwe technologieen. Er zijn echter grote verschillen te bemerken in hoe kinderen gestimuleerd worden om met digitale media om te gaan. Volgens recent Europees onderzoek hebben vooral scholen daarom een grote verantwoordelijkheid bij de ontwikkeling van digitale vaardigheden. In Nederland maken basisscholen steeds meer gebruik van digitale leermiddelen maar de adoptie van digitale technologie in het klaslokaal op dit moment is gefragmenteerd en verloopt niet simultaan. De vraag is waar deze fragmentatie precies vandaan komt en in dit onderzoek wordt geprobeerd deze vraag te beantwoorden door de adoptie van digitale technologie door leerkrachten van jonge kinderen op basisscholen te onderzoeken. Onder jonge kinderen worden kinderen tussen de 4 en 8 jaar oud verstaan, uit de groepen 1 tot en met 6 van het basisonderwijs. De onderzoeksvraag die hieruit voortvloeit en in dit onderzoek beantwoord wordt, is: “Welke opportuniteiten en belemmeringen ervaren leraren in het basisonderwijs in Nederland bij de adoptie van digitale leermiddelen voor kinderen tussen de vier en acht jaar ? ”. Ter beantwoording van de hoofdvraag wordt vertrokken vanuit inzichten uit het ‘Technology Acceptance Model’ (TAM) en het ‘Unified Theory of Acceptance and Use of Technology’-model (UTAUT-model). Deze modellen meten de mate van adoptie aan de hand van gebruiksintenties. Omwille van het exploratieve karakter van deze studie, alsmede uit groeiende ontevredenheid over deze modellen, wordt een stap terug gezet door een meer holistisch perspectief te bieden aan de hand van het domesticatieperspectief. Het empirische deel van het onderzoek is verricht door de uitvoering van een kwalitatieve onderzoeksmethode gebaseerd op diepte interviews met tien leerkrachten uit het Nederlandse basisonderwijs. Door deze interviews thematisch te analyseren zijn belangrijke thema’s in de opportuniteiten en belemmeringen geidentificeerd. Hieruit wordt geconcludeerd dat binnen de thema’s twee duidelijke tegengestelde lijnen te ontdekken zijn: de opportuniteiten spelen zich voornamelijk af op een persoonlijk vlak terwijl de belemmeringen vooral voortkomen vanuit het instituut, in dit geval de school. Aan de hand van deze conclusies is een aantal adviezen samengesteld, voor partijen zoals de scholen maar ook voor ontwikkelaars en de overheid, om de adoptie van digitale leermiddelen door leerkrachten in de toekomst adequater te kunnen ondersteunen.
Performance analysis of a new system for speed control in wind turbines

This paper presents a new system for speed control in wind turbines, the "Electromagnetic Frequency Regulator" - (EFR). One of the most used devices in some topologies to perform the speed control are boxes of mechanical gears, plus a short shelf life, often represent sources of noise and defects. The EFR eliminates the use of these gearboxes, representing a technological breakthrough, making use of a machine adapted induction, where the then known stator of the machine becomes mobile, sympathetic to the turbine shaft. The aim of this study is to evaluate through simulations, efficiency in the speed control for wind variations and reference signals. Simulations showed good results, validating the proposed.
Pedestrian detection system while turning at intersection by surround monitor camera

Recently, demand for active safety systems has been increasing toward zero traffic accident fatality, thus an automated emergency brake system to avoid pedestrian accidents will be commercialized corresponding to Euro-NCAP. However, an effective assistance system for pedestrian accidents while turning at an intersection has not been proposed, though number of the accidents is the second largest after crossing pedestrian accident. We propose the driving assistance system utilizing the surround monitor camera system which is getting popular. Stereo camera configuration utilizing front and side fish eye cameras has been considered to improve detection reliability. However, particular concerns for this configuration are existed, thus we are trying to develop the solution applying machine-learning feature amount in this research. They were preliminarily verified utilizing computer graphics, and then experimented for actual images captured in the real world.
Interference cancellation for collocated wireless radios

To my parents iii ACKNOWLEDGEMENTS I am grateful to many people for the help I have received in different forms over the last few years, allowing me to reach this point. First, I thank Prof. Joy Laskar who as advisor has been positive and resourceful in his guidance. I would also like to acknowledge Prof. John Cressler for his help and advice during past collaborations. Tentzeris and Dr. Chang-Ho Lee, I owe thanks for their time, cooperation and suggestions. To various former and present members of the Microwave Applications Group, I express my gratitude as their support throughout the course of my research has lightened my task. Of these, the mentorship of Dr. Sudipto Chakraborty in the early years and the direction of Dr. Edward Gebara in the later years are especially significant. I appreciate the advice and contribution of Dr. Thanks are also due to Bevin Perumana and Hyoung-Soo Kim for their assistance during times of need. grateful. Most of all, to Dr. Arvind Raghavan who as brother and past member of MAG, has rendered me aid and encouragement in singular fashion, I am indebted. Through industrial internships I have gained insight into the material impact of my education. For the opportunity to work with them and for their technical suggestions, I thank Dr. Scott Forgues at National Semiconductor and Dr. Bruce Schmukler at Quellan. I also benefited from my discussions with Mike Farrell, Mark Dickman and Dr. Andrew Kim who were colleagues at Quellan. Special thanks are iv also due to Patrcik O' Farrell at National Semiconductor for his patience and help on numerous occasions over the years. have been instrumental in creating an atmosphere conducive to the smooth flow of work. I thank the support team for this. Finally, my deepest gratitude is reserved for my parents who with their love and devotion have made this possible. 1 Trend of the number of cellular subscribers in the USA and worldwide. 5 2 Advanced wireless communication network with a layered structure for interoperation. SUMMARY The area of deterministic noise cancellation in mobile radio communication systems is investigated and analyzed. Several interoperation problems in the mobile wireless radio space are identified and interference concerns for the Bluetooth – WLAN networks are characterized and quantified in the physical layer. A mathematical framework has been created for describing interference in the 2.4 GHz band. An adaptive noise suppression system has been …
Modelling of seakeeping ability of FPSO vessels Modelowanie właściwości morskich statków FPSO

Problems concerning preliminary design of FPSO vessels are presented in view of their seakeeping ability. The article analyzes the presently applied approach in which seakeeping quality of FPSO vessels is taken into consideration and discusses possibilities of using this approach at the preliminary stage of design. Besides, the current approach used for predicting such phenomena as heaving, slamming and green water loading is discussed. Slowa kluczowe: FPSO, offshore, projektowanie, wstepny etap projektowania, wlaściwości morskie, zalewanie pokladu, sleming, nurzania Abstrakt W artykule przedstawiono problematyke projektowania wstepnego statkow FPSO, biorąc pod uwage wlaściwości morskie tych statkow. W artykule przeanalizowano aktualnie stosowane podejście, dotyczące uwzgledniania wlaściwości morskich statkow FPSO i mozliwości wykorzystania tego podejścia na wstepnym etapie projektowania. W artykule przedstawiono aktualnie stosowane podejście do prognozowania m.in. nurzan, slemingu i zalewania pokladu statkow FPSO.
Energy Efficiency of Blockchain Technologies

Energy Web (EW) is a global nonprofit organisation accelerating a low-carbon, customer-centric electricity system by unleashing the potential of open-source, decentralised technologies. EW focuses on building core infrastructure and shared technology, speeding the adoption of commercial solutions, and fostering a community of practice. -based renewable energy marketplaces in Asia with Minden in Japan, PTT Group in Thailand, SP Group in Singapore, and Foton in Turkey; in Europe with Engie in France and Accione and Iberdrola in Spain; and in the Americas with PJM in the United States, Mercados Eléctricos in El Salvador, and Eletrobras in Brazil. We can point to other examples for use cases such as virtual power plants, distributed energy resources providing grid flexibility, and digital for lifecycle we
Enhancing MOOC Learners' Video Watching Experience with Real-Time Attention Tracking

A main weakness of the Massive Open Online Learning move-ment is retention: a small minority of learners (on average 5-10%, in extreme cases <1%) that start a MOOC complete it successfully. There are many reasons why learners are unsuccessful, among the most important ones is the lack of self-regulation: learners are often not able to self-regulate their learning behavior. Designing tools that provide learners with a greater awareness of their learning is vital to the future success of MOOC environments. Detecting learners’ loss of focus during learning is particularly important, as this can allow us to intervene and return the learners’ attention to the learning materials. One technological affordance to detect such loss of focus are webcams—ubiquitous pieces of hardware available in almost all laptops today. Recently, researchers have begun to make use of webcams as part of complex machine learning-based solutions to detect inattention or loss of focus based on eye tracking and eye gaze data. However, those approaches tend to have a high detection lag, are inaccurate, and are complex to design and maintain. In contrast, in this paper, we explore the possibility to make use of simple metrics such as gaze presence or face presence to detect a loss of focus in the online learning setting. To this end, we evaluate the performance of three consumer and professional eye-tracking frameworks using a benchmark suite we designed speciﬁcally for this purpose: it contains a set of common xMOOC user activities and behaviours. The results of our study show that already those simple metrics pose a signiﬁcant challenge to current hard- and software-based eye-tracking solutions.
DYNAMIC DETERMINANTS OF THE UPPER TORSO ANGULAR VELOCITY IN GOLF SWING

The purpose of this study was to clarify the dynamic components of the upper torso angular velocity about its longitudinal axis during golf swing. Six right-handed golfers hit a golf ball to the net. Three dimensional kinematic data of swing motions were collected using motion capture system. The dynamic components of the upper torso angular acceleration during swing were calculated as a function of I)jo int toque, 2) gravity, 3) gyro-moment, 4) motion-dependent force, and 5) ground reaction forces. The present study found that the torso joint toque most contributed to the upper torso angular acceleration about its longitudinal axis. On the other hand, the shoulder joint toque and the motion-dependent force of the left arm negatively contributed to the angular acceleration of the upper torso about its longitudinal axis.