Miracle-dz/UniFAR-FTUs huggingface dataset:
Updated results of the FOENIX-CCA2 trial: Efficacy and safety of futibatinib in intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions/rearrangements.

4009 Background: Survival outcomes are historically poor in patients (pts) with advanced/metastatic iCCA, with median overall survival (mOS) times of approximately 1 year with first-line gemcitabine plus cisplatin and approximately 6 months with second-line chemotherapy. Futibatinib, a highly selective, irreversible FGFR1–4 inhibitor, demonstrated efficacy with durable responses in pts with iCCA harboring FGFR2 fusion/rearrangements in the pivotal FOENIX-CCA2 phase 2 study (NCT02052778). At the primary analysis of this trial (data cutoff: October 1, 2020), an objective response rate (ORR) of 41.7% was observed, with a median duration of response (mDOR) of 9.7 mo. Here, we report updated efficacy (including mature OS data) and safety data from the final analysis with an additional 8 mo of follow-up. Methods: FOENIX-CCA2 was a single-arm phase 2 study that enrolled pts with advanced/metastatic iCCA with FGFR2 fusion/rearrangement and progressive disease (PD) after ≥1 prior treatment (tx; including gemcitabine plus platinum-based chemotherapy). Pts received futibatinib 20 mg once daily until PD/intolerability. The primary endpoint was ORR per RECIST v1.1 by independent central review. Secondary endpoints were DOR, disease control rate (DCR), progression-free survival (PFS), OS, safety, and patient-reported outcomes. Results: At the time of the final data cutoff (May 29, 2021), median follow-up was 25.0 mo, and 96/103 pts (93%) had discontinued tx. The median number of tx cycles was 13.0 for a median tx duration of 9.1 mo. The confirmed ORR was 41.7% (43/103) and thereby the same as of the primary analysis, as was the DCR (at 82.5%). The ORR was consistent across pt subgroups. The mDOR was 9.5 mo, and 74% of responses lasted ≥6 mo. mPFS was 8.9 mo, with a 12-mo PFS rate of 35.4%. Mature mOS was 20.0 mo, with a 12-mo OS rate of 73.1% . No new safety signals were identified. Common tx-related adverse events (TRAEs) included hyperphosphatemia (85%), alopecia (33%), dry mouth (30%), diarrhea (28%), dry skin (27%), and fatigue (25%). TRAEs resulted in tx discontinuation in 4 pts (4%). No tx-related deaths occurred. Quality of life was maintained from baseline to tx cycle 13. Conclusions: Findings from the final analysis of FOENIX-CCA2 confirm the results of the primary analysis and reinforce the durable efficacy and continued tolerability of futibatinib in previously treated pts with advanced/metastatic iCCA harboring FGFR2 fusion/rearrangements. Mature OS data were consistent with data from the primary analysis and far exceed historical data in this patient population. Clinical trial information: NCT02052778.
Insecurity and Self-Esteem: Elucidating the Psychological Foundations of Negative Attitudes toward Women

Abstract Political scientists recognize discriminatory attitudes as key to understanding a range of political preferences. Sexism is associated with both explicitly and non-explicitly gendered attitudes. But why do certain individuals display discriminatory attitudes, while others do not? Drawing from psychology, we examine the potential power of an underexplored set of personality traits—secure versus fragile self-esteem—in explaining gendered attitudes and preferences. With an online sample of (N = 487) U.S.-based participants, we find that fragile self-esteem is an important trait underlying individuals’ attitudes: individuals who display a discordant view of self—explicitly positive but implicitly negative—are more likely to hold hostile sexist attitudes and prefer men in leadership; these individuals are also more likely to support the Republican Party and former U.S. president Donald Trump. While present in only a fraction of the population, our results suggest that this trait may be important for understanding the development of discriminatory attitudes toward out-groups.
Teachers’ Perceptions of Inclusive Education in the Johannesburg East District, Gauteng Province

Little is known about the perceptions of teachers towards inclusive education in South Africa. The main objective of this study was to explore teachers’ perceptions of inclusive education in the Johannesburg East District, Gauteng Province. Face to face individual interviews. This study was carried out in South Africa, whereby 15 teachers were interviewed individually. hThis study used a phenomenology design underpinned within interpretive paradigm to get insight on the benefits and challenges teachers encounter regarding the implementation of inclusive education. The data was inductively analysed using the thematic analytic methods that search for themes. The study use convenient and purposive sampling as initial plan to select the teachers that a researcher can easily access. This study revealed that teachers had different perceptions of the implementation of inclusive education.
A Novel efficacious PID controller for processes with inverse response and time delay

Design of controller for the inverse response processes has been a challenge for researchers. Water level control in a steam boiler is one of the best examples, where the time delay and inverse response are inherent. Proportional Integral Derivative(PID) controller is the extensively employed regulator in industries. The present work introduces a new form of PID for the processes which are having time delay and inverse response simultaneously. The proposed PID is associated with a higher order filter. The controller and filter parameters are computed by using polynomial approach. Maximum sensitivity of the control loop is used to determine the tuning parameter. A set-point filter is utilized to diminish the settling time and overshoot in servo response. The suggested method is evaluated by considering several performance indices and bench marking examples. The proposed method is evaluated against the existing methods and tested in real-time scenario also.
Perceived Overqualification and Job Crafting: The Mediating Role of Workplace Anxiety and Moderating Role of Reappraisal

Existing research has indicated the direct effect of perceived overqualification on job crafting, but little is known about the underlying mechanisms and processes through which this occurs. Drawing on motivation and capability-based approaches, we proposed and examined how employees’ perception of their overqualification would influence job crafting by increasing workplace anxiety. Furthermore, we employ emotion regulation literature to predict that reappraisal will mitigate the negative effects of workplace anxiety on job crafting. Using a sample of 1,112 workers from China, our findings showed that (1) perceived overqualification was positively associated with job crafting; (2) perceived overqualification was positively associated with workplace anxiety, which in turn reduced job crafting; and (3) reappraisal emotion regulation weakened the detrimental effect of workplace anxiety on job crafting. Based on these findings, we discussed theoretical and practical implications.
Being a migrant learner in a South African primary school: recognition and racialisation

ABSTRACT This article is an exploration of racialised understandings of migrant learners within the educational space of primary school and the social context of xenophobia in South Africa. These understandings draw from small-scale creative visual research that focused on migrant learners’ perspectives on their school experiences. Framed by the concepts of ‘recognition’ and ‘White privilege’, it uses the spatial encounter between two learners – one racialised as White and one as Black – and draws on elements of storytelling to present their fragmentary, mosaic-like narratives, highlighting two facets of racialisation: the prizing of White migrant identities and the erasure of Black migrant identities. This study contributes to the field of children’s geographies in terms of revealing how migrant primary school children experience the school space differently as differently racialised individuals, as well as how research approaches common in education (picturebooks) and Critical Race Theory (storytelling) can enable such stories to emerge in migration research.
Adaptive fully sequential selection procedures with linear and nonlinear control variates

Abstract A decision-making process often involves selecting the best solution from a finite set of possible alternatives regarding some performance measure, which is known as Ranking-and-Selection (R&S) when the performance is not explicitly available and can only be estimated by taking samples. Many R&S procedures have been proposed considering different problem formulations. In this article, we adopt the classic fully sequential Indifference-Zone (IZ) formulation developed in the statistical literature, and take advantage of the control variates, a well-known variance reduction technique in the simulation literature, to investigate the potential benefits as well as the statistical guarantee by designing a new type of R&S procedure in an adaptive fashion. In particular, we propose a generic adaptive fully sequential procedure that can employ both linear and nonlinear control variates, in which both the control coefficient and sample variance can be sequentially updated as the sampling process progresses. We demonstrate that the proposed procedures provide the desired probability of correct selection in the asymptotic regime as the IZ parameter goes to zero. We then compare the proposed procedures with various existing procedures through the simulation experiments on practical illustrative examples, in which we observe several interesting findings and demonstrate the advantage of our proposed procedures.
P886: AFRICAN AMERICAN PATIENTS WITH SMOLDERING MULTIPLE MYELOMA MAY HAVE A LOWER RISK OF PROGRESSION COMPARED TO WHITE PATIENTS

8045 Background: The incidence of multiple myeloma (MM) is two to threefold higher in African Americans (AAs) compared to whites when adjusted for socioeconomics, age, and sex. However, there is limited information on whether racial background affects the risk of progression from smoldering MM (SMM) to MM. Methods: Patients with SMM presenting to Memorial Sloan Kettering Cancer Center between the years 2000 and 2019 and who identified as either AA or white were included in the study. Baseline characteristics were collected at the time of diagnosis including laboratory, imaging, and pathology reports. Differences in distributions of continuous and discrete characteristics were assessed by Kruskal-Wallis and chi-square tests. Time to progression (TTP) was assessed using the Kaplan-Meier method with log-rank test for comparisons. Univariate and multivariate Cox proportional hazard models were used to estimate effects of risk factors on TTP with hazard ratios (HR) and 95% confidence intervals (CI). Results: A total of 576 patients were included (70 were AA, 12%). Median follow-up time was 3 years in AAs and 4 years in whites. Differences in baseline characteristics between AAs and whites included median age (60 years in AAs vs 64 years in whites, p = 0.01), median hemoglobin level (12.3g/dL in AA vs 12.8g/dL in whites, p = 0.02), and immunoparesis including 1 or 2 uninvolved immunoglobulins (31% and 10% in AAs vs 56% and 27% in whites, p = 0.002). There was no difference in bone marrow plasma cells, M-spike, free light chain ratio, or Mayo-2018 SMM risk score. AA race was associated with a significantly decreased risk of progression in the univariate model (HR 0.57, CI 0.34-0.94). In the multivariate model adjusting for age, sex, and variables associated with an increased risk of progression in the univariate model (bone marrow plasma cells, M-spike, free light chain ratio, immunoparesis and low albumin), AA race remained associated with a decreased risk of progression (HR 0.39, CI 0.16-0.95). Overall, AA patients with SMM had a significantly (p = 0.027) longer median TTP (9.7 vs 6.2 years), and a lower 2-year (12.6% vs 20.1%) and 5-year (34% vs 44.6%) progression rate than whites. Because AA patients were younger at diagnosis, we stratified patients by age group, < 65 vs ≥65 years. In patients < 65 years, there was no difference in progression rate. In patients aged ≥65 years, AA patients continued to have a longer TTP than whites (9.8 vs 5.2 years, p = 0.02). Conclusions: In our retrospective single institution experience, AA patients with SMM had a lower risk of progression to MM compared to whites. Both groups had similar Mayo-2018 risk scores, however, AA patients had a lower degree of immunoparesis at baseline. Future studies are needed to better understand if these differences are explained by differences in disease biology including genomic mechanisms, immune microenvironment, and systemic immune response.
Outcomes of patients with advanced urothelial cancer who develop infection while on treatment with pembrolizumab.

4573 Background: Over the past decade, studies have shown the benefit of immune checkpoint inhibitors (IO) in patients with advanced urothelial cancer. These agents work by reconditioning the adaptive anti-cancer immune response within the tumor microenvironment. Immune-related adverse events have been well documented, but there is limited data evaluating infections in patients treated with IO. We performed a retrospective analysis to assess the incidence of infection and its effect on morbidity and mortality in patients treated with pembrolizumab for advanced urothelial cancer. Methods: Data was collected from a network of 7 hospitals for patients who received pembrolizumab for advanced urothelial cancer from 1/1/2017-8/1/2021. Date of last follow up was 12/1/2021. Covariates compared among infected and non-infected cohorts included age, gender, race, comorbidities, ECOG, anti-infective therapy at IO initiation, and line of therapy (1L, 2L, > 2L). Univariable analysis with reported odds ratio (OR) and 95% confidence interval (CI) was used to assess risk factors for infection. Outcome measures included all-cause emergency department (ED) visits, inpatient and intensive care unit (ICU) admissions, median number of IO cycles, and overall survival (OS). OS was evaluated using the Kaplan-Meier model. All analyses were deemed statistically significant if the p-value was < 0.05. Results: A total of 51 patients were identified. Of these, 34 (66.7%) had at least one documented infection and 17 (33.3%) had no reported infections. Baseline characteristics were similar across cohorts. Compared to non-infected patients, infected patients received fewer cycles of IO (median 4 vs 8, p = 0.016). At last follow-up, 20 (58.8%) patients in the infected cohort and 4 (23.5%) in the non-infected cohort died (p = 0.017). Median OS was 7.4 months (95% CI: 3.4-24.9) among patients with infection while not reached in those without infection (p = 0.014). ED visits (p = 1.00), inpatient admissions (p = 0.21), and ICU admissions (p = 0.17) did not significantly differ between cohorts. Univariable analysis did not identify significant risks among covariates. Conclusions: The incidence of infection in patients treated with pembrolizumab for advanced urothelial cancer is high and associated with fewer cycles of IO therapy and shorter OS. Further study of infectious process prevention is of value to maximize immunotherapy benefit.
Tisotumab vedotin (TV) + pembrolizumab (pembro) in first-line (1L) recurrent or metastatic cervical cancer (r/mCC): Interim results of ENGOT Cx8/GOG 3024/innovaTV 205.

5507 Background: TV monotherapy has received US accelerated approval for previously treated r/mCC with disease progression on or after chemotherapy based on clinically meaningful tumor response rate and duration of response (DOR) reported from the GOG-3023/ENGOT-cx6/innovaTV 204 study (Coleman et al., Lancet Onc. 2021). Recently, the recommended phase 2 dose (RP2D) and feasibility of TV + pembro, TV + carboplatin (carbo), and TV + bevacizumab in r/mCC were reported from the dose-escalation phase (Monk et al, IGCS 2021); interim safety and efficacy data from 2 dose-expansion cohorts, 1L TV + carbo and second-line/third-line (2L/3L) TV + pembro (Vergote et al, ESMO 2021) from the ENGOT-cx8/GOG-3024/innovaTV 205 (NCT03786081) study, were also reported. Here we report interim safety and efficacy results from a third dose-expansion cohort evaluating 1L TV + pembro in patients with r/mCC. Methods: Patients with r/mCC who had not received prior systemic therapy (excluding chemoradiation) for r/mCC were treated with the RP2D of TV 2.0 mg/kg + pembro 200 mg intravenously every 3 weeks. The primary endpoint was investigator-assessed confirmed objective response rate (ORR) per RECIST v1.1; secondary endpoints included DOR, progression-free survival (PFS), overall survival (OS), and safety. Results: 33 pts were treated with 1L TV + pembro (median 6 cycles). At data cutoff (July 1, 2021), median duration of exposure to TV + pembro was 5.1 mo (range 1-17) and median follow-up was 12.2 mo (range 1-17). Confirmed ORR among 32 evaluable patients was 41% (95% CI 24-59), with 3 (9%) complete responses and 10 (31%) partial responses. Median time to response was 1.4 mo (range 1.2-2.8); median DOR was not reached, with response ongoing in 7/13 patients. Median PFS was 5.3 mo (95% CI 4.0-12.2); median OS was not reached. The most common treatment-emergent AEs (TEAEs) were alopecia (61%), diarrhea (55%), epistaxis (49%), conjunctivitis (46%), and nausea (46%). Grade ≥3 TEAEs occurred in 67% of patients, the most common being anemia (12%); asthenia (9%); hypokalemia (9%); and increased alanine aminotransferase, decreased white blood cell count, dyspnea, and acute kidney injury (6% each). Three grade 5 TEAEs were reported of which one, disseminated intravascular coagulation, was considered treatment-related. Prespecified AEs of interest (grade 1-2/grade ≥3) with TV included ocular (58%/9%), peripheral neuropathy (45%/3%), and bleeding (61%/6%). Updated results with longer follow-up for this cohort and the 1L TV + carbo and 2L/3L TV + pembro cohorts will be provided at the meeting. Conclusions: TV + pembro demonstrated encouraging, durable antitumor activity with a manageable and acceptable safety profile as a 1L regimen for patients with r/mCC. This trial is ongoing and final analyses will be reported in the future. Clinical trial information: NCT03786081.
Estimating the prevalence of paediatric chronic pain in Switzerland: an online survey among paediatricians.

BACKGROUND Chronic pain is a frequent complaint in children and adolescents, with great international variation in prevalence. Paediatricians are usually the first-line contact for pain problems in children and might refer patients to other specialists or pain clinics where available. Prevalence estimates of paediatric chronic pain and paediatricians' care experiences in Switzerland are currently lacking. OBJECTIVES The aim of this study was to assess the prevalence of paediatric chronic pain in Swiss paediatrician practices and paediatricians' professional experience and confidence with, and care provision for patients with paediatric chronic pain. METHODS Data were collected in 2019 using a cross-sectional online questionnaire among Swiss paediatricians. Ordinary least square regression analyses and Monte Carlo simulations were applied to estimate the prevalence rate of paediatric chronic pain. Explorative multivariate logistic regression analyses investigated whether sociodemographic and professional factors were associated with paediatricians' confidence in treating and experience with paediatric chronic pain. RESULTS We included 337 paediatricians in our anonymised analyses. The prevalence rate of paediatric chronic pain in our sample was estimated to be between 2.54% and 3.89%. Twenty percent of paediatricians reported feeling confident in treating paediatric chronic pain, 77.2% had referred patients with paediatric chronic pain to another specialist and more than half had at least some experience with paediatric chronic pain. Experience and confidence with treating paediatric chronic pain were associated with male gender. CONCLUSION Our study is the first to estimate the prevalence of paediatric chronic pain by means of a sample of Swiss paediatricians. The prevalence rate was considerably lower than other estimates. Given the lack of training and confidence with treating paediatric chronic pain reported by paediatricians, absence of awareness and resulting under-diagnosis is possible.
Exploratory analysis of the relationship between home health agency engagement in a national campaign and reduction in acute care hospitalization in US home care patients.

RATIONALE, AIMS AND OBJECTIVES To determine whether US home health agencies that intensively engaged with the 2010 Home Health Quality Improvement National Campaign were more likely to reduce acute care hospitalization (ACH) rates than less engaged agencies. METHOD We included all Medicare-certified agencies that accessed Campaign resources in the first month of the Campaign and also responded to an online survey of resource utilization at month two. We used the survey data and item response theory to estimate a latent construct we called engagement with the campaign. ACH rates were calculated from the Centers for Medicare & Medicaid Services Outcome and Assessment Information Set for pre- and post-intervention periods (March-November 2009 and 2010, respectively). RESULTS Staff from 1077 agencies accessed resources in the first month of the Campaign. Of these, 382 provided information about resource use and had 10 or more monthly discharges throughout the measurement periods. Dividing these agencies into quartiles based on engagement score, we found an association between engagement and reduction in ACH rates, P=0.049 (χ(2) for trend). Exploratory path analysis revealed the effect of engagement score on reduction in ACH rate to be partially mediated through reduction in average length of service rates. CONCLUSION We found evidence that early intensity of engagement with the Campaign, as measured through use of activities and resources, was positively associated with improvement. To continue the investigation of this relationship, future work in this and other campaigns should focus on further development of engagement measures.
Prediction of Carotid In-Stent Restenosis by Computed Tomography Angiography Carotid Plaque-Based Radiomics

In-stent restenosis (ISR) after carotid artery stenting (CAS) critically influences long-term CAS benefits and safety. The study was aimed at screening preoperative ISR-predictive features and developing predictive models. Thus, we retrospectively analyzed clinical and imaging data of 221 patients who underwent pre-CAS carotid computed tomography angiography (CTA) and whose digital subtraction angiography data for verifying ISR presence were available. Carotid plaque characteristics determined using CTA were used to build a traditional model. Backward elimination (likelihood ratio) was used for the radiomics model. Furthermore, a combined model was built using the traditional and radiomics features. Five-fold cross-validation was used to evaluate the accuracy of the trained classifier and stability of the selected features. Follow-up angiography showed ISR in 30 patients. Carotid plaque length and thickness were independently associated with ISR (multivariate analysis); regarding the conventional model, the area under the curve (AUC) was 0.84 and 0.82 in the training and validation cohorts, respectively. The corresponding AUC values for the radiomics-based model were 0.87 and 0.82, and those for the optimal combined model were 0.88 and 0.83. Plaque length and thickness could independently predict post-CAS ISR, and the combination of radiomics and plaque features afforded the best predictive performance.