Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative effectiveness of sorafenib, lenvatinib, and nivolumab as first-line systemic therapy for patients with advanced hepatocellular carcinoma and Child-Pugh class B cirrhosis treated at VA Medical Centers.

4102 Background: Up to 90% of cases of hepatocellular carcinoma (HCC) in the U.S. occur in patients with cirrhosis. As prognosis in patients with decompensated cirrhosis may be more related to liver function than tumor stage, patients with Child-Pugh (CP) class B and C cirrhosis are often excluded from randomized trials despite representing up to 30% of patients treated with systemic therapy in clinical practice. While prospective data such as the GIDEON registry and CHECKMATE-040 have demonstrated safety of sorafenib and nivolumab in CP B cirrhosis, studies of comparative effectiveness of sorafenib, lenvatinib, and nivolumab are lacking. Methods: We performed a retrospective cohort study of patients with HCC and CP B cirrhosis at U.S. Veterans Affairs Medical Centers who initiated first systemic therapy with sorafenib, lenvatinib, or nivolumab between 9/22/2017 and 2/13/2021. Overall survival (OS) by first systemic therapy was assessed with Kaplan Meier analysis and Cox proportional hazards modeling with pre-specified candidate covariates and a backward elimination approach for variable selection. Missing data were imputed by multiple imputation with chained equations. Results: Among 401 CP B patients undergoing first systemic therapy, 98% were male, 29% had macrovascular invasion (MVI), 35% had extrahepatic spread (EHS), 57%/29%/13% had CP score 7/8/9, 5% had hepatic encephalopathy, 37% had ascites, 63%/2%/36% had HCV/HBV/non-viral cirrhosis, 63% had prior embolization or ablation, and 35% had ECOG performance status of > = 2. Of these patients, 320 received sorafenib, 33 received lenvatinib, and 48 received nivolumab. In univariate analysis, median OS was 4.8 months (95% CI 3.8 – 6.0; 1 year OS 21.8%) in the sorafenib cohort, 6.9 months (95% CI 4.4 – 8.4 months; 1 year OS 27.8%) in the lenvatinib cohort, and 7.7 months (95% CI 3.9 – 9.1 months; 1 year OS 31.7%) in the nivolumab cohort. Covariates with at least one category significantly associated with survival that were retained in the multivariate model included CP score, MELD-Na, BMI, log(AFP), time from diagnosis to systemic treatment, ECOG performance status, Cirrhosis Comorbidity index, and VA complexity level (all p < 0.05); MVI, EHS, and age were retained in the model as pre-specified despite lack of statistical significance. Compared with sorafenib, nivolumab was associated with significantly lower hazard of death (adjusted HR 0.63; 95% CI 0.43 – 0.91; p = 0.015) while hazard of death for lenvatinib treatment was not significantly different (adjusted HR 0.83; 95% CI 0.54 – 1.28, p = 0.41). Conclusions: Among patients with HCC and CP class B cirrhosis undergoing first systemic therapy, nivolumab was associated with significantly lower hazard of death compared to sorafenib after adjusting for important covariates.
Study EV-103: Update on durability results and long term outcome of enfortumab vedotin + pembrolizumab in first line locally advanced or metastatic urothelial carcinoma (la/mUC).

4528 Background: Significant unmet need remains for people with cisplatin-ineligible (cis-ineligible) locally advanced or metastatic urothelial carcinoma (la/mUC). In the first-line (1L) setting, carboplatin-based regimens have demonstrated poor tolerability, modest objective response rate (ORR) and limited durability. PD-1/PD-L1 inhibitors demonstrate durable responses; however, only a minority of pts achieve a response (ORR 24-29%). Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) delivering the microtubule-disrupting agent monomethyl auristatin E (MMAE) to targeted tumor cells expressing Nectin-4. EV has shown an overall survival benefit versus chemotherapy in previously treated la/mUC. Preclinical studies show that ADCs utilizing MMAE can induce immunogenic cell death and may enhance antitumor immunity. Clinical data suggests the combination of EV + pembrolizumab (P) may have the potential to induce greater antitumor activity compared to either agent alone. Preliminary data on EV + P was previously presented, and the FDA granted breakthrough therapy designation to EV + P for the treatment of pts with 1L cis-ineligible la/mUC in Feb 2020. Here we report updated data with 24.9 months median follow-up. Methods: This multi-cohort EV-103 study (NCT03288545) evaluates the safety/activity of EV + P (Dose Escalation/Cohort A). This report highlights 1L cis-ineligible pts treated with 3-week cycles of EV 1.25 mg/kg (Days 1, 8) and P (Day 1). Endpoints include safety/tolerability, investigator response per RECIST v1.1, DOR, PFS, and OS. Results: As of 13 Oct 2020, the median follow-up for the 45 1L la/mUC pts (median age 69 yrs [51-90]) was 24.9 months. The median number cycles of EV + P was 9 (range 1-34). The most common treatment-related adverse events were peripheral sensory neuropathy (56%, 4% ≥G3), fatigue (51%, 11% ≥G3), and alopecia (49%). There was one death reported as possibly related to study treatment (multiple organ dysfunction syndrome) per investigator assessment. Confirmed ORR is 73.3% (95% CI: 58.1, 85.4) including 17.8% CR and an ORR of 57.1% (8/14) in pts with liver metastasis. The median DOR was 25.6 months (95% CI: 8.3, -). Fifty-three percent of the responders had DOR at 24 months. Additionally, the DCR is 93.3%, the median PFS is 12.3 months (95% CI: 8.0, -), and the median OS is not reached. The OS rate at 24 months is 56.3% (95% CI: 39.8, 69.9). Conclusions: EV + P, a platinum-free option, continues to demonstrate promising activity with a durable response profile in 1L cis-ineligible pts with la/mUC. The safety profile is manageable and stable over time with no new safety signals. Cohort K of EV-103 in cis-ineligible pts with la/mUC is actively randomizing pts to EV monotherapy or EV + P to evaluate the contribution of each agent. Clinical trial information: NCT03288545.
Community knowledge, attitude and practices regarding malaria and long-lasting insecticidal nets in Churachandpur, Manipur

Background: The disease is endemic in many parts of India, especially in the North- Eastern region. A study was done on head of the family’s knowledge, attitude and practice regarding malaria and long-lasting insecticidal bed nets and to determine the association between socio-demographic profile and knowledge and attitude.Methods: A cross-sectional study was conducted in the communities from 3 subcentres namely Pearsonmun, Thingkhangpai and Soipum under Saikot PHC, Churachandpur district of Manipur. House to house survey was carried out and only those who are eligible were interviewed using structured questionnaire. Random sampling and PPS was carried out to select the households head. SPSS was used for analysis.Results: Total of 289 heads of the family was interviewed. The total adequate knowledge score was 30.6% and only 26.3% had favourable attitude towards malaria and long-lasting insecticidal bed nets. There was significant association between marital status, educational qualification, occupation and monthly income with adequacy of knowledge. There was significant association between religion and attitude.Conclusions: Majority of the participants still lacks knowledge and attitude towards the malaria and long-lasting insecticidal nets (LLIN). IEC and awareness campaign should be carried out intensively and further study to be done to see the improvement of knowledge.
Lifting the understanding of trigonometric limits from procedural towards conceptual

The purpose of this paper is to follow the reasoning of high school students when asked to explain the standard trigonometric limit . An observational study was conducted in four different phases in order to investigate if visualization, by means of an interactive technology environment (Geogebra), can contribute in lifting high school students’ understanding from a mere procedural understanding to a combination of conceptual and procedural understanding. The obtained results confirm that the students were able to show a conceptual understanding only after using the digital interactive tool. Through comparing, exploring and self-explaining combined with the use of the interactive tool, the students managed to link different concepts together. The students were able to see and interpret the reason making the angle and relate under certain conditions, thus leading to the standard trigonometric limit .
Mode of action studies with phthalate acid monoesters: pharmacokinetic and pharmacodynamic factors affecting steroidogenesis

REBECCA CLEWELL: Mode of Action Studies with Phthalate Acid Monoesters: Pharmacokinetic and Pharmacodynamic Factors Affecting Steroidogenesis (Under the direction of Melvin Andersen and Louise Ball) The use of phthalate esters in plastics and resulting human exposure has led to concern over potential adverse effects in fetal development. This project provided data and quantitative tools to improve phthalate risk assessments. In vivo, in vitro and in silico experiments evaluated pharmacokinetic and pharmacodynamic factors responsible for antiandrogenic effects of phthalate esters. For pharmacokinetics, plasma and tissue metabolite levels were measured in maternal and fetal rats following DBP administration. A physiologically based pharmacokinetic (PBPK) model was developed for DBP distribution in rat gestation, tested against a variety of data across life-stages, doses and exposure routes, and accurately predicted maternal and fetal plasma MBP levels for acute and repeated dosing. The validated model permitted direct correlation of testes phthalate concentrations and testosterone. When extended to DEHP, the model also predicted MEHP kinetics. For pharmacodynamic evaluation, monoester concentrations were measured in the fetal testes after repeated doses of BBP, DEP, DBP, DEHP, and DMP. An in vitro assay tested the effect of inhibition of steroidogenesis directly in the Leydig cell. The differential ability of the monoesters to cause developmental toxicity was found to result from differences in their pharmacodynamic potency. Finally, we attempted to identify the molecular target for the phthalates in the Leydig cell. The phospholipase A2 (PLA2) inhibitor CQ and MEHP had a
The Role of Proteasome Inhibitors in Multiple Myeloma Bone Disease and Bone Metastasis: Effects on Osteoblasts and Osteocytes

The alterations of bone remodeling are typical of multiple myeloma (MM) patients where the uncoupled and unbalanced bone remodeling caused the onset of osteolytic lesions. Moreover, bone metastasis occurs in the majority of patients with breast and prostate cancer. Skeletal-related events negatively impact on quality of life by increasing the vulnerability to fractures. Several bone-targeting treatments have been developed to control bone pain and pathological fractures, including bisphosphonates and Denosumab. Nevertheless, these agents act by inhibiting osteoclast activity but do not improve bone formation. Proteasome inhibitors (PIs) have shown bone anabolic effects and encouraging results in stimulating osteoblast differentiation and bone healing. Among these, the first-in-class bortezomib and the second-generation PIs, carfilzomib, and ixazomib regulate the bone remodeling process by controlling the degradation of several bone proteins. PIs have been recently proven to also be efficacious in blocking MM-induced osteocyte death providing new possible therapeutic use in the management of bone loss. PIs have significant side effects that limit their use as bone anabolic strategy. Multiple alternative approaches have been made. The conjugation of PIs with bisphosphonates, which can target them to bone, showed good results in terms of bone anabolic activity. However, the clinical implications of these effects require further investigations.
Characterization of Iron-Matrix Composites Reinforced by In Situ TiC and Ex Situ WC Fabricated by Casting

In this study, the effect of microstructural characteristics on the mechanical properties of high-chromium white cast iron-matrix composites reinforced by in situ TiC and ex situ WC was investigated. To this end, two different powder mixtures (Ti + Al + graphite and WC + Fe) were compressed to produce green compacts that were inserted into the mold, before casting. The microstructure of the resulting composites and the base metal was characterized using optical microscopy (OM) and scanning electron microscopy with energy dispersive spectroscopy (SEM/EDS). The microstructural analysis revealed a sound bonding between the composite zone and the base metal. The reinforcement with WC particles showed a homogeneous distribution of the carbide particles, unlike the reinforcement with TiC particles. The mechanical properties of the reinforcements were evaluated using hardness and ball-cratering micro-abrasion tests. The results showed that both reinforcements increase the hardness and wear performance of the base material, which was the best performance achieved by the reinforcement with WC particles.
Leucine-Rich Diet Improved Muscle Function in Cachectic Walker 256 Tumour-Bearing Wistar Rats

Skeletal muscle atrophy occurs in several pathological conditions, such as cancer, especially during cancer-induced cachexia. This condition is associated with increased morbidity and poor treatment response, decreased quality of life, and increased mortality in cancer patients. A leucine-rich diet could be used as a coadjutant therapy to prevent muscle atrophy in patients suffering from cancer cachexia. Besides muscle atrophy, muscle function loss is even more important to patient quality of life. Therefore, this study aimed to investigate the potential beneficial effects of leucine supplementation on whole-body functional/movement properties, as well as some markers of muscle breakdown and inflammatory status. Adult Wistar rats were randomly distributed into four experimental groups. Two groups were fed with a control diet (18% protein): Control (C) and Walker 256 tumour-bearing (W), and two other groups were fed with a leucine-rich diet (18% protein + 3% leucine): Leucine Control (L) and Leucine Walker 256 tumour-bearing (LW). A functional analysis (walking, behaviour, and strength tests) was performed before and after tumour inoculation. Cachexia parameters such as body weight loss, muscle and fat mass, pro-inflammatory cytokine profile, and molecular and morphological aspects of skeletal muscle were also determined. As expected, Walker 256 tumour growth led to muscle function decline, cachexia manifestation symptoms, muscle fibre cross-section area reduction, and classical muscle protein degradation pathway activation, with upregulation of FoxO1, MuRF-1, and 20S proteins. On the other hand, despite having no effect on the walking test, inflammation status or muscle oxidative capacity, the leucine-rich diet improved muscle strength and behaviour performance, maintained body weight, fat and muscle mass and decreased some protein degradation markers in Walker 256 tumour-bearing rats. Indeed, a leucine-rich diet alone could not completely revert cachexia but could potentially diminish muscle protein degradation, leading to better muscle functional performance in cancer cachexia.
The Life Course: An interdisciplinary framework for broadening the scope of research on crowdwork

This paper reports outcomes of a systematic scoping review of methodological approaches and analytical lenses used in empirical research on crowdwork. Over the past decade a growing corpus of publications spanning Social Sciences and Computer Science/HCI have empirically examined the nature of work practices and tasks within crowdwork; surfaced key individual and environmental factors underpinning workers’ decisions to engage in this form of work; developed and implemented tools to improve and extend various aspects of crowdwork, such as the design and allocation of tasks and incentives or workflows within the platforms; and contributed new techniques and know-how on data collection within crowdwork, for example, how to conduct large-scale surveys and experiments in behavioural psychology, economics or education drawing on crowdworker samples. Our initial reading of the crowdwork literature suggested that research had relied on a limited set of relatively narrow methodological approaches, mostly online experiments, surveys and interviews. Importantly, crowdwork research has tended to examine workers’ experiences as snapshots in time rather than studying these longitudinally or contextualising them historically, environmentally and developmentally. This piece-meal approach has given the research community initial descriptions and interpretations of crowdwork practices and provided an important starting point in a nascent field of study. However, the depth of research in the various areas, and the missing pieces, have yet to be systematically scoped out. Therefore, this paper systematically reviews the analytical-methodological approaches used in crowdwork research identifying gaps in these approaches. We argue that to take crowdwork research to the next level it is essential to examine crowdwork practices within the context of both individual and historical-environmental factors impacting it. To this end, methodological approaches that bridge sociological, psychological, individual, collective, online, offline, and temporal processes and practices of crowdwork are needed. The paper proposes the Life Course perspective as an interdisciplinary framework that can help address these gaps and advance research on crowdwork. The paper concludes by proposing a set of Life Course-inspired research questions to guide future studies of crowdwork.
Response of leaf biomass, leaf and soil C:N:P stoichiometry characteristics to different site conditions and forest ages: a case of Pinus tabuliformis plantations in the temperate mountainous area of China

Ecological stoichiometry is an important index that reflects the element cycle and ecosystem stability. In this study, two sites (sunny and shady slopes) and five forest ages (young stage, half-mature stage, near-mature stage, mature stage, and over-mature stage) in a Pinus tabuliformis plantation were chosen to illustrate the effects of forest ages and site conditions on the biomass and stoichiometric characteristics of leaves and soils in the temperate mountainous area of China. Except for young stage, the biomass of the leaves of P. tabuliformis on sunny slopes were higher than those on shady slopes in other forest ages, the average carbon content of the leaves in sunny slopes was higher than that in shady slope, while the average total nitrogen contents and average total phosphorus contents of the leaves showed the opposite of this. The biomass of leaves increased on sunny slopes, and increased first and then decreased in shady slopes with increasing forest ages. The contents of soil total carbon (STC) and soil total nitrogen (STN) decreased with increasing soil depth, while the soil total phosphorus (STP) and soil available phosphorus (SAP) contents displayed the opposite. In addition to SAP, the average content of STC, STN, and STP in shady slopes was higher than that in sunny slopes, and the ratio was the opposite. Except for STC: STN on shady slopes, the other ratios showed a downward trend with an increase in soil depth. Excluding the topsoil, the change trend of STC : STP and STN : STP in shady slopes and sunny slopes was consistent with forest ages. The results showed that forest ages and site conditions had significant effects on leaf biomass. The biomass of the leaves is mainly limited by nitrogen. These results have important significance in improving the refinement of local forestry management of Pinus tabuliformis plantations in the temperate mountainous area of China.
Clinico-etiological profile of hospitalized paediatric patients: COVID-19 and non-COVID-19 in a district hospital of Northern India during lockdown period

End of 2019 witnessed a sudden outbreak of novel coronavirus pneumonia in Wuhan, China, which brought the whole world to a stand-still, presented an unprecedented challenge to public health and economic sector, thereby causing a devastating impact globally. The International Committee on Taxonomy of Viruses (ICTV) named the new coronavirus as severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). The WHO declared coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2, a pandemic health emergency on 11 March 2020. On 22 March 2020, the Government of India ordered a nationwide lockdown for 21 days, limiting movement of the entire 1.3 billion population of India as a preventive measure against the COVID-19 pandemic in India, which was extended later, followed by uplifting of the restrictions in a phased manner. Person-to-person transmission of SARS-CoV-2 occurs primarily through close contact with an infected person, mainly via respiratory droplets and after touching contaminated objects. Additional routes of ABSTRACT
Ocean Surface Wind Speed Dependence and Retrieval From Off‐Nadir CFOSAT SWIM Data

In this study, we analyzed the ocean surface wind speed dependence of off‐nadir data from the Surface Waves Investigation and Monitoring (SWIM) aboard the Chinese‐French Oceanography Satellite (CFOSAT). When the data were analyzed, the SWIM normalized radar cross section (NRCS) at most incidence angles decreased along the NCEP Global Forecast System wind speed. This trend is consistent with that in a Ku‐band geophysical model function at low incidence angles (KuLMOD2S), although there was a systematic bias between the two. The consistency indicates that the SWIM data quality was normal in terms of wind speed dependence. The bias was recalibrated using a numerical weather prediction‐based ocean calibration method and the wind speeds were retrieved from the recalibrated NRCS data using the KuLMOD2S model. Finally, the retrievals at off‐nadir as well as the wind products at nadir were validated using collocated CFOSAT scatterometer (CSCAT) wind measurements. When the results were validated, the retrievals at 0.5° were consistent with the averaged wind products at nadir and both had a root mean square difference (RMSD) around 1.4 m/s compared to the CSCAT winds. Moreover, the winds retrieved from the SWIM data at most incidence angles were in good agreement with the CSCAT winds,and the RMSD values were within 2.0 m/s for incidence angles less than 7.5°, although the retrieval accuracy was poor at larger incidence angles. These results demonstrate that the SWIM data at incidence angles below 7.5° have an ability to retrieve the wind speed.