bluuebunny/crossref_metadata_2025_split huggingface dataset:
The assessment of procedural skills in physiotherapy education: a measurement study using the Rasch model
Authors: Sattelmayer Karl Martin , Jagadamma Kavi C. , Sattelmayer Franziska , Hilfiker Roger , Baer Gillian 
Published: May 2020

Abstract
Background
Procedural skills are a key element in the training of future physiotherapists. Procedural skills relate to the acquisition of appropriate motor skills, which allow the safe application of clinical procedures to patients. In order to evaluate procedural skills in physiotherapy education validated assessment instruments are required. Recently the assessment of procedural skills in physiotherapy education (APSPT) tool was developed. The overall aim of this study was to establish the structural validity of the APSPT. In order to do this the following objectives were examined: i) the fit of the items of APSPT to the Rasch-model, ii) the fit of the overall score to the Rasch model, iii) the difficulty of each test item and iv) whether the difficulty levels of the individual test items cover the whole capacity spectrum of students in pre-registration physiotherapy education.

Methods
For this observational cross-sectional measurement properties study a convenience sample of 69 undergraduate pre-registration physiotherapy students of the HES-SO Valais-Wallis was recruited. Participants were instructed to perform a task procedure on a simulated patient. The performance was evaluated with the APSPT. A conditional maximum likelihood approach was used to estimate the parameters of a partial credit model for polytomous item responses. Item fit, ordering of thresholds, targeting and goodness of fit to the Rasch model was assessed.

Results
Item fit statistics showed that 25 items of the APSPT showed adequate fit to the Rasch model. Disordering of item thresholds did not occur and the targeting of the APSPT was adequate to measure the abilities of the included participants. Undimensionality and subgroup homogeneity were confirmed.

Conclusion
This study presented evidence for the structural validity of the APSPT. Undimensionality of the APSPT was confirmed and therefore presents evidence that the latent dimension of procedural skills in physiotherapy education consists of several subcategories. However, the results should be interpreted with caution given the small sample size.
Mandible lymphoma: an aggressive osteolytic lesion
Authors: Oliveira Camila S. , de Lima Matheus H. A. , D’Almeida Costa Felipe , da Cruz Perez Danyel Elias , da Silveira da Rocha Talita Maira Bueno , Alves Fabio Abreu 
Published: May 2020

Abstract
Background
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-hodgkin’s lymphoma. In oral cavity represents approximately 2% of all malignancies.

Case presentation
This report describes a rare mandibular involvement of DLBCL. A 56 year-old man was referred for evaluation of left mandible pain. In the anamnesis, the patient informed to be treating tooth pain in lasting 6 months. On oral evaluation, an intense mobility of the left mandibular second molar and a swelling in posterior left mandible were observed. Computed tomography showed a large osteolytic lesion affecting both mandibular body and ramus. An incisional biopsy was performed and according to histopathological and imumnohistochemical features, DLBCL was diagnosed. The treatment consisted of 8 cycles of R-CHOP and adjuvant radiotherapy. He is asymptomatic after 6 years.

Conclusion
This case showed a rare bone presentation of DLBCL and such tumor should be considered as differential diagnosis of osteolytic lesion of the mandible.
Methanol fixation for scanning electron microscopy of plants
Authors: Kim Ki Woo 
Published: May 2020

AbstractPlant specimens for scanning electron microscopy (SEM) are commonly treated using standard protocols. Conventional fixatives consist of toxic chemicals such as glutaraldehyde, paraformaldehyde, and osmium tetroxide. In 1996, methanol fixation was reported as a rapid alternative to the standard protocols. If specimens are immersed in methanol for 30 s or longer and critical-point dried, they appear to be comparable in preservation quality to those treated with the chemical fixatives. A modified version that consists of methanol fixation and ethanol dehydration was effective at preserving the tissue morphology and dimensions. These solvent-based fixation and dehydration protocols are regarded as rapid and simple alternatives to standard protocols for SEM of plants.
Phase I study of teclistamab, a humanized B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in relapsed/refractory multiple myeloma (R/R MM).
Authors: Usmani Saad Zafar , Mateos Maria-Victoria , Nahi Hareth , Krishnan Amrita Y. , van de Donk Niels W.C.J. , San Miguel Jesus , Oriol Albert , Rosiñol Laura , Chari Ajai , Adams Homer , Girgis Suzette , Wang Lin Shun Xin , Stephenson Tara , Kemmerer Kristy , Smit Jennifer , Elsayed Yusri A. , Infante Jeffrey R. , Goldberg Jenna D. , Banerjee Arnob , Garfall Alfred L. 
Published: May 2020

100 Background: Teclistamab (JNJ-64007957) is a bispecific BCMA x CD3 antibody that induces T cell-mediated cytotoxicity against BCMA-expressing myeloma cells. Initial results from an ongoing study of teclistamab in RRMM (NCT03145181) are presented. Methods: Pts have MM and are RR to standard therapies. Primary objective for part 1 is to identify a recommended phase 2 dose(s). Multiple intravenous (iv) doses ± priming doses were explored. Adverse events (AEs) were graded per CTCAE v4.03 and cytokine release syndrome (CRS) per Lee et al 2014. Response was investigator-assessed using IMWG criteria; minimal residual disease (MRD) in bone marrow was assessed by next generation sequencing. Results: As of 31 Jan 2020, 66 pts had received iv teclistamab (0.3–270 µg/kg). Median age was 64 y (24–82), median prior therapies was 6 (2–14), 97% triple-class exposed, 83% triple-class refractory, and 38% penta-drug refractory. Most common treatment-related AEs (all grade) were CRS (56%), neutropenia (26%), and anemia (23%). CRS events were all grade 1–2 and generally confined to initial doses. 8% of pts had treatment-related neurotoxicity (3% grade ≥3), and 9% had infusion related reaction. Infection-related AEs were reported in 61% of pts (21% grade ≥3). 2 dose-limiting toxicities were reported: grade 4 delirium (resolved after 16 days) and grade 4 thrombocytopenia (resolved after 1 day). 36% of pts had treatment-related grade ≥3 AEs; neutropenia (20%) and anemia (14%) were most frequent. Only 1 grade 5 AE was reported (respiratory failure in the setting of pneumonia deemed unrelated by the investigator). PK results indicate that the half-life of teclistamab supports weekly dosing. On-target pharmacodynamic activity (T cell redistribution and activation along with transient release of cytokines) was observed at doses ≥9.6 µg/kg. Cytokine production was modulated with step-up dosing while T cell activation was maintained. 65 pts were evaluable for response. Activity was observed starting at treatment doses ≥38.4 µg/kg, with 20/52 (38%) pts achieving a response. At the highest dose, 7/9 (78%) pts responded (1 response pending confirmation). Of MRD-evaluable pts who had complete response, 2/2 were MRD negative at 10−6 with treatment ongoing > 12 mo. Conclusions: Teclistamab has manageable safety across all doses explored. A 78% overall response rate was observed at the highest weekly treatment dose in pts with advanced RRMM, supporting further evaluation of teclistamab in expansion cohorts. Clinical trial information: NCT03145181.
Long-term benefit of adjuvant dabrafenib + trametinib (D+T) in patients (pts) with resected stage III BRAF V600–mutant melanoma: Five-year analysis of COMBI-AD.
Authors: Hauschild Axel , Dummer Reinhard , Santinami Mario , Atkinson Victoria , Mandalà Mario , Kirkwood John M. , Chiarion Sileni Vanna , Larkin James M. G. , Nyakas Marta , Dutriaux Caroline , Haydon Andrew Mark , Robert Caroline , Mortier Laurent , Schachter Jacob , Dasgupta Kohinoor , Gasal Eduard , Tan Monique , Long Georgina V. , Schadendorf Dirk 
Published: May 2020

10001 Background: Previous results of the COMBI-AD trial (NCT01682083) showed a significant relapse-free survival (RFS) benefit with 12 mo of adjuvant D+T vs placebo (PBO) in pts with high-risk resected stage III BRAF V600E/K–mutant melanoma. In the primary analysis, 3-year RFS rates with D+T vs PBO were 58% vs 39% (hazard ratio [HR], 0.47 [95% CI, 0.39-0.58]; P < .001). An interim analysis of overall survival (OS) yielded 3-year OS rates of 86% with D+T vs 77% with PBO (HR, 0.57 [95% CI, 0.42-0.79]). Here we report data from 5-year analyses including long-term RFS and an updated cure rate model. Methods: COMBI-AD is a randomized, Phase III trial evaluating 12 mo of adjuvant D 150 mg twice daily + T 2 mg once daily vs 2 matched PBOs in pts with resected stage III BRAF V600E/K–mutant melanoma. Pts were stratified by BRAF status and disease stage (per AJCC 7 criteria). The primary endpoint is RFS; secondary endpoints include OS and distant metastasis–free survival (DMFS). A Weibull mixture cure rate model was applied to estimate the fraction of pts who will remain relapse free in the long term. As all patients had completed treatment by the time of the primary analysis, updated safety analyses were not performed. Results: This analysis represents a median follow-up of 60 mo for the D+T arm and 59 mo for the PBO arm. As of the data cutoff (Nov 8, 2019), 190 of 438 pts in the D+T arm and 262 of 432 pts in the PBO arm had an RFS event. Median RFS was not reached (NR; 95% CI, 47.9 mo-NR) with D+T vs 16.6 mo (95% CI, 12.7-22.1 mo) with PBO (HR, 0.51 [95% CI, 0.42-0.61]). The 4- and 5-year RFS rates were 55% (95% CI, 50%-60%) and 52% (95% CI, 48%-58%) with D+T vs 38% (95% CI, 34%-43%) and 36% (95% CI, 32%-41%) with PBO. These findings match those estimated by the cure rate model. The RFS benefit with D+T was evident across all AJCC 7 substages (HR [95% CI]: IIIA, 0.61 [0.35-1.07]; IIIB, 0.50 [0.37-0.67]; IIIC, 0.48 [0.36-0.64]). Median DMFS was NR in either arm but favored D+T (HR, 0.55 [95% CI, 0.44-0.70]). OS was not updated at this data cutoff as the prespecified number of events for the final OS analysis had not yet occurred. Conclusions: This 5-year analysis confirms the long-term benefit of adjuvant D+T in pts with resected stage III BRAF V600E/K–mutant melanoma. Clinical trial information: NCT01682083.
CheckMate 067: Long-term outcomes in patients with mucosal melanoma.
Authors: Shoushtari Alexander Noor , Wagstaff John , Ascierto Paolo Antonio , Butler Marcus O. , Lao Christopher D. , Marquez-Rodas Ivan , Chiarion-Sileni Vanna , Dummer Reinhard , Ferrucci Pier F. , Lorigan Paul , Smylie Michael , van Dijck Wim , Rizzo Jasmine I. , Hodi F. Stephen , Larkin James M. G. 
Published: May 2020

10019 Background: Mucosal melanoma is a rare but aggressive malignancy with a poor prognosis. Here we report 5-y outcomes in a subgroup of patients with mucosal melanoma treated in CheckMate 067 with nivolumab plus ipilimumab (NIVO+IPI), NIVO alone, or IPI alone. Methods: Patients with previously untreated stage III or IV melanoma were randomized 1:1:1 to receive NIVO 1 mg/kg + IPI 3 mg/kg for 4 doses Q3W followed by NIVO 3 mg/kg Q2W, NIVO 3 mg/kg Q2W + placebo, or IPI 3 mg/kg Q3W for 4 doses + placebo until progression or unacceptable toxicity. Mucosal histology was not a stratification factor, and patients with mucosal melanoma were identified by local investigators in the study. Descriptive subgroup analyses were performed to evaluate efficacy (objective response rate [ORR], progression-free survival [PFS], overall survival [OS]), and safety. Results: A total of 79 patients with mucosal melanoma were treated. With a minimum follow-up of 60 mo, NIVO+IPI treatment was associated with the highest 5-y ORR (43% [vs 30% with NIVO and 7% with IPI]), PFS (29% [vs 14% and 0%, respectively]), and OS (36% [vs 17% and 7%, respectively]; Table), consistent with trends in the intent-to-treat (ITT) population; however, efficacy outcomes were generally less favorable overall relative to the ITT population. Complete response rates were higher with NIVO+IPI (14%) relative to monotherapy (NIVO, 4%; IPI, 0%) in patients with mucosal melanoma. Safety outcomes, including the grade 3/4 treatment-related adverse event rates of 54%, 26%, and 25%, respectively, were similar to the ITT population. Conclusions: This 5-y analysis showed that patients with mucosal melanoma in CheckMate 067 had similar safety outcomes but poorer long-term efficacy vs the ITT population. Patients with mucosal melanoma treated with NIVO+IPI appeared to have more favorable survival outcomes than those treated with NIVO or IPI alone. Novel therapies are needed to further improve long-term benefit in patients with mucosal melanoma. Clinical trial information: NCT01844505. [Table: see text]
Heterogeneous response and irAE patterns in advanced melanoma patients treated with anti-PD-1 monotherapy from different ethnic groups: Subtype distribution discrepancy and beyond.
Authors: Bai Xue , Quach Henry , Cann Christopher G , Zhang Michael , Kim Michelle S. , Kasumova Gyulnara G. , Si Lu , Tang Bixia , Cui Chuanliang , Yang Xiaoling , Wei Xiaoting , Cohen Justine Vanessa , Lawrence Donald P. , Sharova Tatyana , Frederick Dennie T. , Flaherty Keith , Sullivan Ryan J. , Boland Genevieve Marie , Johnson Douglas Buckner , Guo Jun ,   MGH Nurse Practitioner Group
Published: May 2020

10020 Background: Programmed cell death receptor-1 (PD-1) monotherapy is the standard first line therapy for advanced cutaneous melanoma, with efficacy, toxicity, and their correlations well established. Yet these remain poorly characterized for non-Caucasians and for certain rarer melanoma subtypes. Methods: Clinical data from melanoma patients treated with anti-PD-1 monotherapy between 2009 and 2018 was collected retrospectively from three independent institutions from the US and China. Tumor response, survival outcome, and organ/system-specific immune-related adverse effects (irAEs) were directly compared between different subgroups. Results: Among 626 patients, 411 were Caucasian, 214 non-Caucasian; 369 had cutaneous melanoma, and 257 other subtypes. Both ethnicity and melanoma subtype were independently associated with benefit and irAEs. In multivariate analyses, Caucasians had significantly higher objective response rate (ORR) (OR 2.0, 95% CI 1.1-3.5), but this did not translate into a survival advantage (PFS, HR 0.8, 95% CI 0.6-1.1; OS, HR 1.0, 95% CI 0.7-1.4); melanoma of unknown primary shared similar response and survival profile with cutaneous, while acral (ORR, OR 0.4, 95% CI 0.2-0.9; PFS, HR 1.6, 95% CI 1.1-2.2; OS, HR 1.3, 95% CI 0.8-1.9), mucosal (ORR, OR 0.4, 95% CI 0.2-0.9; PFS, HR 1.4, 95% CI 1.0-2.0; OS, HR 1.7, 95% CI 1.1-2.6) and ocular (ORR, OR 0.1, 95% CI 0-0.6; PFS, HR 2.3, 95% CI 1.4-3.6; OS, HR 2.2, 95% CI 1.3-3.6) melanomas had inferior outcomes. Non-Caucasian cutaneous patients had a significantly worse ORR than Caucasians with cutaneous melanoma (P < .01). Distinct irAE patterns were observed, exemplified by lower incidence of most irAEs (although more frequent pneumonitis) in Caucasians, and higher and lower liver irAE incidence in ocular and mucosal melanomas, respectively. Endocrine, musculoskeletal and skin irAEs were associated with improved PFS and OS across ethnicities and nearly all melanoma subtypes, whereas heterogeneity existed for other irAE types. Conclusions: Ethnicity and melanoma subtype are associated with distinct response patterns, survival outcomes, and irAE profiles in the setting of anti-PD-1 monotherapy. More research is needed to elucidate the molecular and immunologic determinants of these variable outcomes.
Phase I trial of autologous cMET-directed CAR-t cells administered intravenously in patients with melanoma & breast carcinoma.
Authors: Shah Payal D , Huang Alexander Chan Chi , Xu Xiaowei , Zhang Paul J. , Orlowski Robert , Matlawski Tina , Shea Joanne , Cervini Amanda , Amaravadi Ravi K. , Tchou Julia C. , Schuchter Lynn Mara , Wherry E. John , Linette Gerald P. , Mick Rosemarie , Kulikovskaya Irina , Lacey Simon F. , Plesa Gabriela , June Carl H. , Vonderheide Robert H. , Mitchell Tara C. 
Published: May 2020

10035 Background: Advanced relapsed/refractory melanoma and metastatic triple-negative breast cancer are lethal diseases for which effective therapies are limited. We conducted a pilot phase I clinical trial (NCT03060356) to establish the safety and feasibility of intravenous autologous chimeric antigen receptor (CAR) T cell immunotherapy targeting cMET, a cell-surface antigen that is highly expressed in these cancers. Methods: Subjects had metastatic or unresectable melanoma (Mel) or triple-negative breast cancer (BC) with ≥30% expression of cMET on archival tissue or screening biopsy. Eligible subjects had measurable disease and progression on at least 1 prior therapy. Patients (pts) received up to 6 doses (1x108 total T-cells per dose) of RNA electroporated anti-cMET CAR T cells over a 2-week period without antecedent lymphodepleting chemotherapy. Subjects underwent pre- and post-infusion biopsies. The primary objective was to determine feasibility and safety of treatment. Results: 77 subjects (39 mel, 38 BC) were prescreened for tumor cMET expression and 37 (17 mel, 20 BC) met the eligibility threshold. Seven pts (4 BC, 3 Mel) received cMET-directed CAR T infusions on study. Mean age was 50 years (35-64); median (M) ECOG 0 (0-1); M prior lines of chemotherapy/immunotherapy were 4/0 for BC pts and 1/3 for Mel pts. 6 of 7 pts received all planned CAR T cell infusions, and 1 received 5 infusions. 5 pts experienced grade (G) 1 or G 2 toxicity that was possibly or definitely related to study. Toxicities occurring in ≥1 pt included: anemia (n = 3), fatigue (n = 2), and malaise (n = 2). No G ≥3 toxicities or cytokine release syndrome were observed. No pts discontinued therapy due to toxicity. Best response was stable disease in 4 pts (2 BC, 2 Mel) and PD in 3 pts (2 BC, 1 Mel). Messenger RNA signals corresponding to CAR T cells were detected by RT-PCR in the peripheral blood of all pts during the infusion period and in 2 pts after the infusion period. 6 pts underwent baseline biopsy and 4 pts underwent post-infusion biopsy. Immunohistochemical stains of CD3, CD4, CD8, CD163, L26, PD1, PDL1, Foxp3, Ki67, Granzyme B and Phospho-S6 were performed on pre- and post-treatment tissue biopsies and are being evaluated. Conclusions: Intravenous administration of RNA-electroporated cMET-directed CAR T cells was safe and feasible. Future directions include examination of this target using a lentiviral construct in combination with lymphodepleting chemotherapy. Clinical trial information: NCT03060356.
Spatial proximity of CD8 T cells to tumor cells as an independent biomarker for response to anti-PD-1 therapy.
Authors: Slagter Maarten , Rozeman Elisa A. , Ding Huiwen , Versluis Judith M. , Valenti Mesele , Peters Dennis , Broeks Annegien , Rooijen Charlotte van , Horlings Hugo , Haanen John B. A. G. , Hooijberg Erik , Wessels Lodewyk F. A. , Blank Christian U. , Schumacher Ton N. 
Published: May 2020

10038 Background: Only a subset of advanced melanoma patients respond to anti-PD-1 (aPD1) monotherapy. Upfront identification of (non-)responsiveness would help guide first-line treatment decisions, prevent overtreatment and unnecessary risk for toxicities. T cell density and expression of T cell related genes have been associated with response to aPD1, but are imperfect predictors. We investigated whether spatial proximity of CD8 T cells to tumor cells improves upon the predictive value of T cell density alone. Methods: Pretreatment tumor specimens from melanoma patients treated with aPD1 in the Netherlands Cancer Institute were stained for DAPI, SOX10/Melan-A, CD4, CD8, FOXP3 and PD-1 by multiplex immunofluorescence. Sections were imaged on Vectra and analyzed using HALO to optimize marker thresholds and demarcate tumor and stroma. T cell proximity to tumor cells was evaluated as difference in area under the curve between i) a spatial G-function quantifying T cell density around tumor cells in tumor areas and ii) analogous null distributions obtained by random permutation of cell labels. This assessment of co-clustering is independent of cell density and heterogeneity therein and does not reflect repulsion of T cells to stromal/marginal areas. Clinical characteristics, RECIST response and survival were collected from patient records. Associations between T cell density, T cell proximity to Sox10/Melan-A+ tumor cells, other clinical biomarkers (LDH, M stage and WHO performance status) and response were examined in a Bayesian hierarchical logistic regression. Results: Tumor specimens of 98 patients were included, of whom 45 were treated with aPD1 as first-line therapy and 33 had an objective response. CD8 T cell proximity to tumor cells was associated with response in an independent, comparatively strong, and tissue dependent manner (cutaneous tissue: 2.78 [2.45, 3.17], visceral: 2.30 [1.95, 2.72], lymphoid: 2.12 [1.88, 2.40], format: maximal posteriori odds ratio [89% equal-tailed credibility interval]), in a multivariate model correcting for CD8 T cell density (1.74 [1.62, 1.88]), LDH (1.93 [1.72, 2.16]), M stage (0.92 [0.87, 0.98]) and WHO performance status (0.79 [0.72, 0.88]). Our model achieved an area under the ROC curve of 77.7%, whereas an analogous model omitting the proximity variable achieved 73.1%. Conclusions: Our analyses show that spatial proximity of CD8 T cells to tumor cells functions as an independent biomarker for response to aPD1 and suggests that preexisting CD8 T cell tumor reactivity is reflected by this spatial proximity.