bluuebunny/crossref_metadata_2025 huggingface dataset:
Rare Pleomorphic Liposarcoma Presented as Jejunal Obstruction
Authors: Al-Attar Mohammad , Jnawali Anup , Yang Michelle
Published: June 2023

Pleomorphic liposarcoma (PLS) is typically found in the lower and upper extremities. PLS arising in the gastrointestinal (GI) tract is extremely rare. Here, we reported a case of a 71-year-old female with a history of rectal adenocarcinoma presenting with small bowel obstruction. Small bowel resection was performed and revealed a 7.8 cm transmural mass in the jejunum. Histology reviewed a heterogenous epithelioid malignant tumor with intracytoplasmic fatty droplets scalloping the nucleus consistent with lipoblasts in some cells and others with numerous PAS/diastase+intracytoplasmic eosinophilic globules. Scattered multinucleated giant cells were also present. Mitotic count was up to 80/10 HPFs including some bizarre mitotic figures, and Ki67 proliferation index was approximately 60%. Immunohistochemistry demonstrated that the malignant cells were negative for pancytokeratin, CD117, DOG1, SMA, desmin, MyoD1, ERG1, CD34, CD31, SOX10, Melan A, and S100. INI1 was retained. Beta-catenin showed normal membranous staining. P53 was diffusely positive suggestive of mutant phenotype. Fluorescence in situ hybridization (FISH) assay was negative for MDM2 amplification and DDIT3 rearrangement. The overall morphologic and immunohistochemical features supported a diagnosis of high-grade pleomorphic liposarcoma. Diagnosis of PLS can be challenging due to its rarity in GI tract and lack of specific biomarkers, and histomorphology with identification of lipoblasts remains the gold standard.
A Novel Back-Analysis Approach for the External Loads on Shield Tunnel Lining in Service Based on Monitored Deformation
Authors: Lin Wei , Li Pan , Xie Xiongyao , Cao Yuyang , Zhang Yangbin
Published: June 2023

The maintenance of in-service shield tunnel lining has become a critical issue in recent decades due to the rapid development of the metro system in China. The external load is one of the most important factors influencing the deformation and performance of the in-service shield tunnels. It is hard to evaluate the external load since it is influenced by complex factors. And the arbitrary-distributed external load is not considered in the existing theories. A novel back-analysis approach for evaluating the external load using the deformation of tunnel lining was proposed based on Betti’s theorem. The theoretical rationality of the proposed method is analyzed, and the workflow is provided. The data and simulation models for a model test were adopted to validate the effectiveness and accuracy of the proposed method. The results show that the external loads can be back-analyzed with satisfying accuracy and low computational cost. Then, the practical application was conducted for an in-service shield tunnel. In addition, the workflow combined with laser scanning and back analysis was proposed for evaluating the practical loads. The proposed approach can be used for the back analysis of the external loads based on lining deformation scanned inside tunnels, with good performance.
KCF-Based Identification Approach for Vibration Displacement of Double-Column Bents under Various Earthquakes
Authors: Cai Wei , Xie Wen , He Tiantao
Published: June 2023

Vibration displacements are one of the most significant indicators in the health monitoring and condition assessment of bridges in the life cycle. The traditional monitoring means, such as contact sensors, have relatively high-cost and limited points for displacement measurement of bridges. This paper proposes a low-cost and non-contact monocular vision system based on the KCF algorithm to accurately and timely identify the vibration displacement of bridges. A conversion method associated with a scale ratio was established to cope with the loss of depth information in images when a monocular camera is used to monitor multiple targets in different depths of the field. A series of shaking table tests on a two-column pier with energy dissipation beams were conducted to verify the feasibility, accuracy, effectiveness, and robustness of the KCF-based identification approach. The results showed that the vibration displacements of the column identified by the monocular vision system based on the KCF algorithm are almost consistent with the measurement results obtained by the laser displacement sensors. The peak displacement discrepancies between both measurement methods are within 6% for all cases with different shaking amplitudes and earthquake waves. The RMSE of the displacement histories between both measurement methods is very low. The corresponding frequency spectra contents identified by the monocular vision system based on the KCF algorithm match well with the measurement counterparts recorded from the laser displacement sensors.
Supplementary Fig. 4 from A Phase 1/2 Multicenter Randomized Trial of Local Ablation plus Toripalimab versus Toripalimab Alone for Previously Treated Unresectable Hepatocellular Carcinoma
Authors: Zhou Chunhui , Li Yan , Li Jiaping , Song Botian , Li Hanfeng , Liang Bin , Gu Shanzhi , Li Haiping , Chen Changyong , Li Sai , Peng Changli , Liu Fei , Xiao Juxiong , Long Xueying , Li Ping , Xiong Zhengping , Yi Xiaoping , Liao Weihua , Shi Liangrong
Published: June 2023

Supplementary Fig. 4 A. Progression-free survival by PD-L1 status. B. Overall survival by PD-L1 status. Dot marks indicate censored data.
Supplementary Fig. 1 from A Phase 1/2 Multicenter Randomized Trial of Local Ablation plus Toripalimab versus Toripalimab Alone for Previously Treated Unresectable Hepatocellular Carcinoma
Authors: Zhou Chunhui , Li Yan , Li Jiaping , Song Botian , Li Hanfeng , Liang Bin , Gu Shanzhi , Li Haiping , Chen Changyong , Li Sai , Peng Changli , Liu Fei , Xiao Juxiong , Long Xueying , Li Ping , Xiong Zhengping , Yi Xiaoping , Liao Weihua , Shi Liangrong
Published: June 2023

Supplementary Fig. 1 Forest plot of subgroup analysis for progression-free survival (A) and overall survival (B).
Table S1 from Maveropepimut-S, a DPX-Based Immune-Educating Therapy, Shows Promising and Durable Clinical Benefit in Patients with Recurrent Ovarian Cancer, a Phase II Trial
Authors: Dorigo Oliver , Oza Amit M. , Pejovic Tanja , Ghatage Prafull , Ghamande Sharad , Provencher Diane , MacDonald Lisa D. , Torrey Heather , Kaliaperumal Valarmathy , Ebrahimizadeh Walead , Hirsch Heather A. , Bramhecha Yogesh , Villella Jeannine , Fiset Stephan
Published: June 2023

Representativeness of Study Participants
Supplementary Fig. 2 from An Open-label Phase I Study of GDC-0927 in Postmenopausal Women with Locally Advanced or Metastatic Estrogen Receptor–Positive Breast Cancer
Authors: Chandarlapaty Sarat , Dickler Maura N. , Perez Fidalgo Jose Alejandro , Villanueva-Vázquez Rafael , Giltnane Jennifer , Gates Mary , Chang Ching-Wei , Cheeti Sravanthi , Fredrickson Jill , Wang Xiaojing , Collier Ann , Moore Heather M. , Metcalfe Ciara , Lauchle Jennifer , Humke Eric W. , Bardia Aditya
Published: June 2023

Supplementary Fig. S2. The PGR z-score for six patients analyzed in Fig. 4.
Supplementary Fig. 1 from An Open-label Phase I Study of GDC-0927 in Postmenopausal Women with Locally Advanced or Metastatic Estrogen Receptor–Positive Breast Cancer
Authors: Chandarlapaty Sarat , Dickler Maura N. , Perez Fidalgo Jose Alejandro , Villanueva-Vázquez Rafael , Giltnane Jennifer , Gates Mary , Chang Ching-Wei , Cheeti Sravanthi , Fredrickson Jill , Wang Xiaojing , Collier Ann , Moore Heather M. , Metcalfe Ciara , Lauchle Jennifer , Humke Eric W. , Bardia Aditya
Published: June 2023

Supplementary Fig. S1. Study scheme.
Supplementary Data 1 from An Open-label Phase I Study of GDC-0927 in Postmenopausal Women with Locally Advanced or Metastatic Estrogen Receptor–Positive Breast Cancer
Authors: Chandarlapaty Sarat , Dickler Maura N. , Perez Fidalgo Jose Alejandro , Villanueva-Vázquez Rafael , Giltnane Jennifer , Gates Mary , Chang Ching-Wei , Cheeti Sravanthi , Fredrickson Jill , Wang Xiaojing , Collier Ann , Moore Heather M. , Metcalfe Ciara , Lauchle Jennifer , Humke Eric W. , Bardia Aditya
Published: June 2023

Supplementary Tables S1, S2, and S3.
Supplementary Data 1 from Comparative Genomic Analysis of Pancreatic Acinar Cell Carcinoma (PACC) and Pancreatic Ductal Adenocarcinoma (PDAC) Unveils New Actionable Genomic Aberrations in PACC
Authors: Florou Vaia , Elliott Andrew , Bailey Matthew H. , Stone David , Affolter Kajsa , Soares Heloisa P. , Nevala-Plagemann Chris , Scaife Courtney , Walker Phillip , Korn W. Michael , Lou Emil , Shroff Rachna T. , Hosein Peter J. , Garrido-Laguna Ignacio
Published: June 2023

Supplementary table
Data from A Phase 1/2 Multicenter Randomized Trial of Local Ablation plus Toripalimab versus Toripalimab Alone for Previously Treated Unresectable Hepatocellular Carcinoma
Authors: Zhou Chunhui , Li Yan , Li Jiaping , Song Botian , Li Hanfeng , Liang Bin , Gu Shanzhi , Li Haiping , Chen Changyong , Li Sai , Peng Changli , Liu Fei , Xiao Juxiong , Long Xueying , Li Ping , Xiong Zhengping , Yi Xiaoping , Liao Weihua , Shi Liangrong
Published: June 2023

AbstractPurpose:
To assess the safety and efficacy of local ablation plus PD-1 inhibitor toripalimab in previously treated unresectable hepatocellular carcinoma (HCC).
Patients and Methods:
In the multicenter, two-stage, and randomized phase 1/2 trial, patients were randomly assigned to receive toripalimab alone (240 mg, every 3 weeks), subtotal local ablation followed by toripalimab starting on post-ablation day 3 (Schedule D3), or on post-ablation day 14 (Schedule D14). The first endpoint of stage 1 was to determine which combination schedule could continue and progression-free survival (PFS) as the primary endpoint for stage 1/2.
Results:
A total of 146 patients were recruited. During stage 1, Schedule D3 achieved numerically higher objective response rate (ORR) than Schedule D14 for non-ablation lesions (37.5% vs. 31.3%), and was chosen for stage 2 evaluation. For the entire cohort of both stages, patients with Schedule D3 had a significantly higher ORR than with toripalimab alone (33.8% vs. 16.9%; P = 0.027). Moreover, patients with Schedule D3 had improved median PFS (7.1 vs. 3.8 months; P < 0.001) and median overall survival (18.4 vs. 13.2 months; P = 0.005), as compared with toripalimab alone. In addition, six (9%) patients with toripalimab, eight (12%) with Schedule D3, and 4 (25%) with Schedule D14 developed grade 3 or 4 adverse events, and one patient (2%) with Schedule D3 manifested grade 5 treatment-related pneumonitis.
Conclusions:
In patients with previously treated unresectable HCC, subtotal ablation plus toripalimab improved the clinical efficacy as compared with toripalimab alone, with an acceptable safety profile.
Data from An open-label phase I study of GDC-0927 in postmenopausal women with locally advanced or metastatic estrogen receptor positive breast cancer
Authors: Chandarlapaty Sarat , Dickler Maura N. , Perez Fidalgo Jose Alejandro , Villanueva-Vázquez Rafael , Giltnane Jennifer , Gates Mary , Chang Ching-Wei , Cheeti Sravanthi , Fredrickson Jill , Wang Xiaojing , Collier Ann , Moore Heather M. , Metcalfe Ciara , Lauchle Jennifer , Humke Eric W. , Bardia Aditya
Published: June 2023

Abstract
Background: GDC-0927 is a novel, potent, non-steroidal, orally bioavailable, selective estrogen receptor (ER) degrader (SERD) that induces tumor regression in ER+ breast cancer xenograft models. Methods: This phase I dose-escalation multicenter study enrolled postmenopausal women with ER+/HER2- metastatic breast cancer to determine the safety, pharmacokinetics, and recommended phase II dose of GDC-0927. Pharmacodynamics was assessed with [18F]-fluoroestradiol (FES) PET scans. Results: Forty-two patients received GDC-0927 once daily. The maximum tolerated dose was not reached. The most common adverse events (AEs) regardless of causality were nausea, constipation, diarrhea, arthralgia, fatigue, hot flush, back pain, and vomiting. There were no deaths, grade 4/5 AEs, or treatment-related serious AEs. Two patients experienced grade 2 AEs of special interest of deep vein thrombosis and jugular vein thrombosis, both considered unrelated to GDC-0927. Following dosing, approximately 1.6-fold accumulation was observed, consistent with the observed half-life and dosing frequency. There were no complete or partial responses. Pharmacodynamics was supported by >90% reduction in FES uptake and a ~40% reduction in ER expression, suggesting ER degradation is not the mechanistic driver of ER antagonism. Twelve patients (29%) achieved clinical benefit; 17 patients (41%) showed a confirmed best overall response of stable disease. Baseline levels of ER and PR protein and mutant ESR1 ctDNA did not correlate with clinical benefit. Conclusions: GDC-0927 appeared to be well-tolerated with pharmacokinetics supporting once daily dosing. There was evidence of target engagement and preliminary evidence of anti-tumor activity in heavily pretreated patients with advanced/metastatic ER+/HER2- breast cancer with and without ESR1 mutations.
Data from An Open-label Phase I Study of GDC-0927 in Postmenopausal Women with Locally Advanced or Metastatic Estrogen Receptor–Positive Breast Cancer
Authors: Chandarlapaty Sarat , Dickler Maura N. , Perez Fidalgo Jose Alejandro , Villanueva-Vázquez Rafael , Giltnane Jennifer , Gates Mary , Chang Ching-Wei , Cheeti Sravanthi , Fredrickson Jill , Wang Xiaojing , Collier Ann , Moore Heather M. , Metcalfe Ciara , Lauchle Jennifer , Humke Eric W. , Bardia Aditya
Published: June 2023

AbstractPurpose:
GDC-0927 is a novel, potent, nonsteroidal, orally bioavailable, selective estrogen receptor (ER) degrader that induces tumor regression in ER+ breast cancer xenograft models.
Patients and Methods:
This phase I dose-escalation multicenter study enrolled postmenopausal women with ER+/HER2− metastatic breast cancer to determine the safety, pharmacokinetics, and recommended phase II dose of GDC-0927. Pharmacodynamics was assessed with [18F]-fluoroestradiol (FES) PET scans.
Results:
Forty-two patients received GDC-0927 once daily. The MTD was not reached. The most common adverse events (AE) regardless of causality were nausea, constipation, diarrhea, arthralgia, fatigue, hot flush, back pain, and vomiting. There were no deaths, grade 4/5 AEs, or treatment-related serious AEs. Two patients experienced grade 2 AEs of special interest of deep vein thrombosis and jugular vein thrombosis, both considered unrelated to GDC-0927. Following dosing, approximately 1.6-fold accumulation was observed, consistent with the observed half-life and dosing frequency. There were no complete or partial responses. Pharmacodynamics was supported by >90% reduction in FES uptake and an approximately 40% reduction in ER expression, suggesting ER degradation is not the mechanistic driver of ER antagonism. Twelve patients (29%) achieved clinical benefit; 17 patients (41%) showed a confirmed best overall response of stable disease. Baseline levels of ER and progesterone receptor protein and mutant ESR1 circulating tumor DNA did not correlate with clinical benefit.
Conclusions:
GDC-0927 appeared to be well tolerated with pharmacokinetics supporting once-daily dosing. There was evidence of target engagement and preliminary evidence of antitumor activity in heavily pretreated patients with advanced/metastatic ER+/HER2− breast cancer with and without ESR1 mutations.
Data from Maveropepimut-S, a DPX-based immune-educating therapy, shows promising and durable clinical benefit in patients with recurrent ovarian cancer, a phase 2 trial
Authors: Dorigo Oliver , Oza Amit M. , Pejovic Tanja , Ghatage Prafull , Ghamande Sharad , Provencher Diane , MacDonald Lisa D. , Torrey Heather , Kaliaperumal Valarmathy , Ebrahimizadeh Walead , Hirsch Heather A. , Bramhecha Yogesh , Villella Jeannine , Fiset Stephan
Published: June 2023

Abstract
Purpose: Patients with platinum resistant ovarian cancer (OvCa) respond poorly to existing therapies. Hence there is a need for more effective treatments. Methods: The DeCidE1 trial is a multicenter, randomized, open-label, single-arm phase 2 study to evaluate the safety and effectiveness of maveropepimut-S (MVP-S) with cyclophosphamide (CPA) in patients with recurrent ovarian cancer. Median follow-up for evaluable subjects was 4.4 months. Data were collected from March 2019 to June 2021. Subjects received two injections of 0.25 mL MVP-S 3 weeks apart, followed by one 0.1 mL doses, every 8 weeks up to progression. Oral CPA, 50 mg twice daily, was administered in repeating weekly on and off cycles. Results: Twenty-two patients were enrolled. Median age was 58 years (38-78 years). Among the evaluable population, ORR was 21% (90% CI, 7.5%-41.9%), with a DCR of 63% (90% CI, 41.8%-81.3%), including 4 (21%) patients with partial responses, 8 (42%) stable disease, and 7 (37%) progressive disease. The ORRs were consistent across subgroups based on platinum-sensitivity, and DCR was higher in the platinum-resistant subpopulation. Four stable disease patients maintained clinical benefit up to 25 months. Most treatment related adverse events (TRAEs) were grade 1 and 2 (87% of unique events). Most common AEs were injection site reactions. Eight subjects reported grade 3 and no grade 4 AEs. Survivin-specific T cell responses were observed in treated patients with clinical benefit. Conclusions: MVP-S with intermittent low-dose CPA is well-tolerated, with clinical benefit for patients with recurrent OvCa. Observed responses are irrespective of the platinum status.
Data from Maveropepimut-S, a DPX-Based Immune-Educating Therapy, Shows Promising and Durable Clinical Benefit in Patients with Recurrent Ovarian Cancer, a Phase II Trial
Authors: Dorigo Oliver , Oza Amit M. , Pejovic Tanja , Ghatage Prafull , Ghamande Sharad , Provencher Diane , MacDonald Lisa D. , Torrey Heather , Kaliaperumal Valarmathy , Ebrahimizadeh Walead , Hirsch Heather A. , Bramhecha Yogesh , Villella Jeannine , Fiset Stephan
Published: June 2023

AbstractPurpose:
Patients with platinum-resistant ovarian cancer respond poorly to existing therapies. Hence there is a need for more effective treatments.
Methods:
The DeCidE1 trial is a multicenter, randomized, open-label, single-arm phase II study to evaluate the safety and effectiveness of maveropepimut-S with cyclophosphamide in patients with recurrent ovarian cancer. Median follow-up for evaluable subjects was 4.4 months. Data were collected from March 2019 to June 2021. Subjects received two injections of 0.25 mL maveropepimut-S 3 weeks apart, followed by one 0.1-mL doses, every 8 weeks up to progression. Oral cyclophosphamide, 50 mg twice daily, was administered in repeating weekly on and off cycles.
Results:
Twenty-two patients were enrolled. Median age was 58 years (38–78 years). Among the evaluable population, the objective response rate (ORR) was 21% [90% confidence interval (CI), 7.5%–41.9%], with a disease control rate (DCR) of 63% (90% CI, 41.8%–81.3%), including 4 (21%) patients with partial responses, 8 (42%) stable disease, and 7 (37%) progressive disease. The ORRs were consistent across subgroups based on platinum sensitivity, and DCR was higher in the platinum-resistant subpopulation. Four SD patients maintained clinical benefit up to 25 months. Most treatment-related adverse events (TRAE) were grade 1 and 2 (87% of unique events). Most common AEs were injection site reactions. Eight subjects reported grade 3 and no grade 4 AEs. Survivin-specific T-cell responses were observed in treated patients with clinical benefit.
Conclusions:
Maveropepimut-S with intermittent low-dose cyclophosphamide is well-tolerated, with clinical benefit for patients with recurrent ovarian cancer. Observed responses are irrespective of the platinum status.
Data from Spatial Immunoprofiling of Adenoid Cystic Carcinoma Reveals B7-H4 Is a Therapeutic Target for Aggressive Tumors
Authors: de Sousa Luana G. , McGrail Daniel J. , Lazar Neto Felippe , Li Kaiyi , Marques-Piubelli Mario L. , Ferri-Borgogno Sammy , Dai Hui , Mitani Yoshitsugu , Spardy Burr Nicole , Cooper Zachary A. , Kinneer Krista , Cortez Maria Angelica. , Lin Shiaw-Yih , Bell Diana , El-Naggar Adel , Burks Jared , Ferrarotto Renata
Published: June 2023

Abstract
Purpose: Adenoid cystic carcinoma (ACC) is a heterogeneous malignancy, and no effective systemic therapy exists for metastatic disease. We previously described two prognostic ACC molecular subtypes with distinct therapeutic vulnerabilities, ACC-I and ACC-II. In this study, we explored the ACC tumor microenvironment (TME) using RNA-sequencing and spatial biology to identify potential therapeutic targets. Experimental Design: Tumor samples from 62 ACC patients with available RNA-sequencing data that had been collected as part of previous studies were stained with a panel of 28 validated metal-tagged antibodies. Imaging mass cytometry (IMC) was performed using the Fluidigm Helios CyTOF instrument and analyzed with Visiopharm software. The B7-H4 antibody-drug conjugate AZD8205 was tested in ACC patient–derived xenografts (PDXs). Results: RNA deconvolution revealed that most ACCs are immunologically “cold”, with approximately 30% being “hot”. ACC-I tumors with a poor prognosis harbored a higher density of immune cells; however, spatial analysis by IMC revealed that ACC-I immune cells were significantly restricted to the stroma, characterizing an immune-excluded TME. ACC-I tumors overexpressed the immune checkpoint B7-H4, and the degree of immune exclusion was directly correlated with B7-H4 expression levels, an independent predictor of poor survival. Two ACC-I/B7-H4-high PDXs obtained 90% complete responses to a single dose of AZD8205, but none were observed with isotype-conjugated payload or in an ACC-II/B7-H4 low PDX. Conclusions: Spatial analysis revealed that ACC subtypes have distinct TMEs, with enrichment of ACC-I immune cells that are restricted to the stroma. B7-H4 is highly expressed in poor-prognosis ACC-I subtype and is a potential therapeutic target.
Clinical Activity and Exploratory Resistance Mechanism of Milademetan, an MDM2 Inhibitor, in Intimal Sarcoma with MDM2 Amplification: An Open-Label Phase Ib/II Study
Authors: Koyama Takafumi , Shimizu Toshio , Kojima Yuki , Sudo Kazuki , Okuma Hitomi Sumiyoshi , Shimoi Tatsunori , Ichikawa Hitoshi , Kohsaka Shinji , Sadachi Ryo , Hirakawa Akihiro , Yoshida Akihiko , Ando Reiko Makihara , Ueno Toshihide , Yanagaki Mitsuru , Matsui Naoko , Nakamura Kenichi , Yamamoto Noboru , Yonemori Kan
Published: June 2023

Intimal sarcoma is an extremely rare, life-threatening malignant neoplasm. Murine double minute 2 (MDM2) amplification is observed in >70% of intimal sarcomas. Milademetan, an MDM2 inhibitor, may provide clinical benefit in this patient population. We conducted a phase Ib/II study in patients with MDM2-amplified, wild-type TP53 intimal sarcoma as a substudy of a large nationwide registry for rare cancers in Japan. Milademetan (260 mg) was administered orally once daily for 3 days every 14 days, twice in a 28-day cycle. Of 11 patients enrolled, 10 were included in the efficacy analysis. Two patients (20%) showed durable responses for >15 months. Antitumor activity correlated with TWIST1 amplification (P = 0.028) and negatively with CDKN2A loss (P = 0.071). Acquired TP53 mutations were detected in sequential liquid biopsies as a novel exploratory resistance mechanism to milademetan. These results suggest that milademetan could be a potential therapeutic strategy for intimal sarcoma.

Significance:

Strategies to optimize outcomes could include the use of new biomarkers (TWIST1 amplification and CDKN2A loss) to select patients with MDM2-amplified intimal sarcoma who might benefit from milademetan and combination with other targeted treatments. Sequential liquid biopsy of TP53 can be used to evaluate disease status during treatment with milademetan.

See related commentary by Italiano, p. 1765.

This article is highlighted in the In This Issue feature, p. 1749
Supplementary Figure 4 from Adjuvant Therapy with Oncolytic Adenovirus Delta-24-RGDOX After Intratumoral Adoptive T-cell Therapy Promotes Antigen Spread to Sustain Systemic Antitumor Immunity
Authors: Jiang Hong , Shin Dong Ho , Yi Yanhua , Fan Xuejun , Gumin Joy , He Jiasen , Gillard Andrew G. , Lang Frederick F. , Gomez-Manzano Candelaria , Fueyo Juan
Published: June 2023

The effect of combining pmel-1 T cells and Delta-24-RGDOX. A, A cartoon depiction of the treatment scheme for schedule (left) and positions of tumor implantation, T-cell and virus injection (right). s.c.: subcutaneously; i.t.: intratumorally. B, Plots of the bioluminescence of the tumors from the indicated treatment groups. C, Survival plots of the treatment groups. n = 9 except n = 8 for combination group. RGDOX: Delta-24-RGDOX. ns: not significant (p > 0.05); **: p<0.01. log-rank test.
Supplementary Figure 2 from Adjuvant Therapy with Oncolytic Adenovirus Delta-24-RGDOX After Intratumoral Adoptive T-cell Therapy Promotes Antigen Spread to Sustain Systemic Antitumor Immunity
Authors: Jiang Hong , Shin Dong Ho , Yi Yanhua , Fan Xuejun , Gumin Joy , He Jiasen , Gillard Andrew G. , Lang Frederick F. , Gomez-Manzano Candelaria , Fueyo Juan
Published: June 2023

Expression of TCRs in CD8+ T cells from pmel-1 (A, gp100-Tet+) or OT-I (B, OVA-Tet+) transgenic mice. Splenocytes from the mice were stained with tetramers binding with TCR specific for gp100 (pmel-1) or OVA (OT-I), and antibody against CD8. Stained cells were analyzed with flow cytometry. The numbers in upright corner of the dot plots indicate the frequency (% of splenocytes) of gp100-targeting (A) or OVA-targeting (B) in CD8+ T cells.
Supplementary Figure 1 from Adjuvant Therapy with Oncolytic Adenovirus Delta-24-RGDOX After Intratumoral Adoptive T-cell Therapy Promotes Antigen Spread to Sustain Systemic Antitumor Immunity
Authors: Jiang Hong , Shin Dong Ho , Yi Yanhua , Fan Xuejun , Gumin Joy , He Jiasen , Gillard Andrew G. , Lang Frederick F. , Gomez-Manzano Candelaria , Fueyo Juan
Published: June 2023

gp100 and ovalbumin (OVA) expression in indicated mouse melanoma cell lines. Cell lysates were analyzed with immunoblotting. GAPDH levels are shown as a protein loading control.
FIGURE 4 from Adjuvant Therapy with Oncolytic Adenovirus Delta-24-RGDOX After Intratumoral Adoptive T-cell Therapy Promotes Antigen Spread to Sustain Systemic Antitumor Immunity
Authors: Jiang Hong , Shin Dong Ho , Yi Yanhua , Fan Xuejun , Gumin Joy , He Jiasen , Gillard Andrew G. , Lang Frederick F. , Gomez-Manzano Candelaria , Fueyo Juan
Published: June 2023

CD62 L downregulation in CD8+ leukocytes from treated (Tumor 1) and untreated (Tumor 2) subcutaneous tumors caused by TAA-specific T cells and/or Delta-24-RGDOX. Leukocytes from the tumors in the treatment groups, as depicted in Fig. 3A, were profiled with flow cytometry. Representative flow cytometry histograms showing CD62 L expression on CD8+ leukocytes (A, left), endogenous OVA-specific CTLs (A, right, CD8+ OVA-Tet+) and pmel-1 T cells (B) from tumors of the indicated treatment groups. C, Quantification of the mean fluorescence intensity (MFI) of CD62 L on the cells mentioned in A and B. Leukocytes were from grouped tissue (4 to 7 mice/group) and processed in triplicate. The columns in the graphs represent the mean ± SD (n = 3). RGDOX: Delta-24-RGDOX; T cells: pmel-1 T cells. ns, not significant (P > 0.05); *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001. Two-tailed Student t test.
FIGURE 3 from Adjuvant Therapy with Oncolytic Adenovirus Delta-24-RGDOX After Intratumoral Adoptive T-cell Therapy Promotes Antigen Spread to Sustain Systemic Antitumor Immunity
Authors: Jiang Hong , Shin Dong Ho , Yi Yanhua , Fan Xuejun , Gumin Joy , He Jiasen , Gillard Andrew G. , Lang Frederick F. , Gomez-Manzano Candelaria , Fueyo Juan
Published: June 2023

Increased inflammation in treated (Tumor 1) and untreated distant (Tumor 2) tumors induced by combining TAA-specific T cells and Delta-24-RGDOX. A, A cartoon depiction of the treatment scheme for schedule (left) and positions of tumor implantation, T-cell and virus injection (right). s.c.: subcutaneously; i.t.: intratumorally. Leukocytes from the tumors in the treatment groups were profiled with flow cytometry. B, Quantification of leukocyte (CD45+ cells) density in the tumors from each treatment group. Representative flow cytometry dot plots (C) and their quantification (D) to show CD8+ leukocyte frequencies in the indicated treatment groups. E, Quantification of CD8+ leukocyte density in the tumors from each treatment group. Leukocytes were from grouped tissue (4 to 7 mice/group) and processed in triplicate. The numbers in the upright corner of the dot plots in C indicate the frequency of CD8+ cells (percent of leukocytes). The columns in the graphs represent the mean ± SD (n = 3). RGDOX: Delta-24-RGDOX; T cells: pmel-1 T cells; ****, P < 0.0001. Two-tailed Student t test.
FIGURE 1 from Adjuvant Therapy with Oncolytic Adenovirus Delta-24-RGDOX After Intratumoral Adoptive T-cell Therapy Promotes Antigen Spread to Sustain Systemic Antitumor Immunity
Authors: Jiang Hong , Shin Dong Ho , Yi Yanhua , Fan Xuejun , Gumin Joy , He Jiasen , Gillard Andrew G. , Lang Frederick F. , Gomez-Manzano Candelaria , Fueyo Juan
Published: June 2023

Tumor tropism of TAA-specific T cells after localized intratumoral injection. A, A cartoon depiction of the treatment scheme for schedule (left) and positions of tumor implantation and T-cell injection (right). s.c.: subcutaneously; i.t.: intratumorally; i.c.: intacranially. B–D, Flow cytometry profiling of leukocytes from the indicated tissues from the treatment groups to show the distribution of pmel-1 T cells (Thy1.1+) in the subcutaneous tumors (B, left: representative flow cytometry dot plots; right: quantification of Thy1.1+ cells in the tumors), brain hemispheres (C) and peripheral lymphoid organs (D). The numbers in the upright corner of the dot plots indicate the frequency of Thy1.1+ cells (% of CD8+ leukocytes). Leukocytes were from grouped tissue (PBS: n = 3; pmel-1 T cells: n = 5) and processed in triplicate. The columns in the graphs represent the mean ± SD (n = 3). w/o tumor: without tumor; inguinal LN: inguinal lymph node; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001. Two-tailed Student t test.
Peripheral Ophthalmic Artery Aneurysm Associated with Multifocal Intracranial and Extracranial Aneurysms: Case Report and Literature Review
Authors: Hong Zixin , Noonan Jonathan E , Mitchell Peter J , Hardy Thomas G
Published: June 2023

Peripheral ophthalmic artery aneurysm is a rare disease entity. We review the relevant literature and report a case of fusiform aneurysm involving the entire intraorbital ophthalmic artery in association with multiple intracranial and extracranial aneurysms, diagnosed on digital subtraction angiography. The patient suffered irreversible blindness secondary to compressive optic neuropathy which did not improve after a 3-day trial of intravenous methylprednisolone. Autoimmune screen was normal. The underlying cause is unknown.
Plasmacytoma of the Head and Neck: Case Series and Review of the Literature
Authors: Lamb Meredith M. , Zeatoun Abdullah , Stack Taylor J. , Kim Sulgi , Albastoni Sara , Singer Bart , Klatt-Cromwell Cristine , Senior Brent A. , Kimple Adam J. , Thorp Brian D.
Published: June 2023

Solitary plasmacytoma is a rare neoplasm characterized by localized proliferation of monoclonal plasma cells and is classified as solitary bone or solitary extramedullary plasmacytoma. Here, we present two rare cases of plasmacytoma of the head and neck. The first is a 78-year-old male who presented with a 3-month history of epistaxis and progressive obstruction of the right nasal passage. Computerized tomography (CT) imaging revealed a mass in the right nasal cavity with destruction to the maxillary sinus. An excisional biopsy was performed revealing anaplastic plasmacytoma. The second is a 64-year-old male with a past medical history significant for prostate cancer who presented with a 2-month history of left ear pain and progressive non-tender temporal swelling. A PET/CT revealed a highly avid, destructive, and lytic left temporal mass with no other evidence of distant disease. A left temporal craniectomy and infratemporal fossa dissection revealed plasma cell dyscrasia with monoclonal lambda in situ hybridization. Although plasmacytomas are uncommon tumors of the head and neck, they may mimic other entities that require different treatment. Prompt and accurate diagnosis is critical for appropriate therapeutic decisions and prognosis.
A review of the tribe Noviini (Coleoptera: Coccinellidae) of the Indian subcontinent
Authors: POORANI J.
Published: June 2023

The tribe Noviini (Coleoptera: Coccinellidae) is economically important as its members are mainly predators of giant scales belonging to the family Monophlebidae and occasionally, mealybugs (Pseudococcidae). At present, 17 species of the tribe, all belonging to the sole recognized genus Novius Mulsant, are known from the Indian region. An illustrated account of the Indian species of Novius is presented here with brief diagnostic accounts, illustrations of the genitalia and details on the distribution, host insects and associated host plants. Life stages of the species are also illustrated wherever available. An updated checklist of Novius species of the Indian subcontinent is provided.
Are the recently described fossil Mole Crickets of Myanmar amber real gryllotalpids? (Orthoptera: Gryllotalpidae & Gryllidae)
Authors: CADENA-CASTAÑEDA OSCAR J. , LIU YI-JIAO , YU ZHE-YUAN , HU TIAN-HAO , WU SHI-YANG , HE ZHU-QING
Published: June 2023

We report five new Myanmar amber specimens attributable to “Mole Cricket” †Pherodactylus rectanguli n. comb., hitherto regarded as a Mole Cricket (Orthoptera: Grylloptalpidae). The new material includes two adult males, two adult females, and one nymph. The specimens are redescribed, and additional new characters are provided for their delimitation and corresponding species identification. We carry out a comparison between these new specimens with other taxa of mole crickets from Myanmar amber and extant true crickets. The result indicates that some species merely represent different nymphal development stages or adults of †Pherodactylus rectanguli n. comb., however, they were misidentified as different species. We also treated genera †Tresdigitus n. syn. and †Chunxiania n. syn. as synonyms of genus †Pherodactylus Poinar, Su & Brown, 2020, and treat †Tresdigitus gracilis Jiang, Xu, Jarzembowski & Xiao, 2022 n. syn. and †Chunxiania fania n. syn. as synonyms of †Pherodactylus rectanguli n. comb. †Burmagryllotalpa longa is valid, because its shape of the pronotum curved without lateral carinae. The morphological convergences and specializations of subterranean dwelling species are discussed. The robust fore tibia and long apical spurs of †P. micromorphus, †P. rectanguli n. comb. and †B. longa are insufficient evidence for an assignment to the family Gryllotalpidae. Instead, we suggest place them into the subfamily Gryllinae (Gryllidae), tribe Sclerogryllini, and group them into their own subtribe Pherodactylina n. subtr.. A key to the identification of recent and fossil Sclerogryllini is also provided. Their taxonomy and morphology are discussed.
Two species of hackled-orb web spider genus Hyptiotes (Araneae, Uloboridae) from Guangxi, China
Authors: HUANG ZONGGUANG , YIN HAIQIANG , CAI QU , XU XIANG
Published: June 2023

Two species of the genus Hyptiotes Walckenaer 1837 are described from Guangxi Zhuang Autonomous Region, China, including a new species, Hyptiotes nonggang n. sp. (♂♀), and a known species, Hyptiotes paradoxus (C. L. Koch, 1834) (♂♀) which is the type species. Detailed descriptions and illustrations of the two species are provide, and a map of collecting localities of them in China is also provided.
Micro characteristics and macro performance of HR3C/T92 steel joints after 100000 hours service at high temperature
Authors: Liu Xinying , Lu Kun , Zhang Zhongwu , Zhang Lei , Su Xiaoyang
Published: June 2023

In this study, HR3C/T92 dissimilar steel joint samples were taken from ultra-supercritical 1000 MW units of domestic power plants, and the microstructures, tensile property, hardness, and antioxidant performance as well as safety assessment of the welded joints were studied using OMR,
SEM, UTM, and other equipment. The results reflected that the micromorphology characteristics and hardness of HR3C/T92 dissimilar steel joints are unaffected after 100000 hours of service. Nevertheless, tensile and impact tests revealed that the joints are prone to brittle fracture. Tensile
fracture occurred on the weld fusion line of T92 steel, and the impact absorption energy was lower than the standard requirements. HR3C steel exhibited superior oxidation resistance and corrosion resistance. Moreover, there was no observable oxide layer on the inner wall of the pipe, and the
outermost layer of the outer wall had an intact structure. The inner wall of the T92 steel pipe had a 300-μm-thick oxide layer comprising Fe2O3 and (Fe, Cr) oxides. The extrapolated performance of the dissimilar steel joint samples after operation for 200000
hours at high temperatures also met the service requirements.
Effect of astragaloside on expression of smac, cytochrome C and caspase-3 in hepatic tissue of acute hepatic failure induced by D-Gal NLPS
Authors: Qin Lingli , Lu Jinxi , Ji Sun
Published: June 2023

This study assessed astragaloside IV’s effect on liver Smac, Cytochrome C (Cyt-C) and Caspase-3 expression in acute liver failure in mice. Mice were randomly assigned into normal group, model group, model+astragaloside (1%) group and model+astragaloside (5%) group. Mice were given
by gavage of astragaloside (50 mg/kg/d, 250 mg/kg/d) for 2 d before making the model in model + astragaloside group and model+astragaloside group. Equal dose of normal saline was administrated to the other groups. Except for the normal group, mice in the other groups were intraperitoneally
injected with D-GalN/LPS for 48 h. The mice were at the end killed after the final intraperitoneal injection for 2 hours. Hepatic apoptosis and expressions of hepatic Smac, Cyt-C and caspase-3 were then analyzed. Mice exhibited less hepatocyte apoptosis and lower content of hepatic Cyt-C expression
in both the model+astragaloside and model+astragaloside groups (P <0.01). D-GalN/LPS significantly enhanced Caspase-3 and Smac mRNA. Moreover, astragaloside suppressed the activity of Caspase-3 and decreased hepatic Smac mRNA expression in mice (P <0.01). Astragaloside
IV can reduce the content of Cyt-C and down-regulate the expression of Smac and caspase-3, thereby protecting acute liver failure.
miR-15a nanometric compound restrains the activity and adhesion of Hela cells through survivin signal pathway
Authors: Pan Xin , Cai Honghong , Tang Xiuwu
Published: June 2023

We herein studied the mechanism of miR-15a nanometer compound (NMC) by assessing its activity and adhesion in Hela cells through survivin signal pathway. The miR-15a nanometer compound was prepared and Hela-S3 cells were divided into miR-15a group, miR-NC group and NC group for in
vitro studies. Proliferative activity was detected with MTT method while invasive ability was detected with Transwell closet method. Adhesive capacity was compared and Survivin and Caspase-3 protein expressions were detected with Western blot assay. Results showed that, grain size of miR-15a
NMC was reduced along with increased N/P value, and Zeta potential was negative, and was converted into positive charge along with increased N/P value. The particle size distribution was uniform and potential was moderated when the N/P value was twenty. The proliferation
ability and invasive capacity in miR-15a group was reduced significantly along with lower A540 value and higher adhesive ability as well as reduced survivin and increased Caspase-3 level. The proliferative, invasive and adhesive capacity of Hela cells were all restrained by the miR-15a NMC,
and apoptosis was prompted through restraining of the survivin signaling pathway, so as to affect the occurrence and development of cervical carcinoma.
Circ_0015756 modulates high glucose-induced podocyte injury through miR-136 in diabetic nephropathy
Authors: Zhang Haitao , Liu Zhuo , Li Qiong
Published: June 2023

This study was to discuss the impact of Circ_0015756 on podocyte injury in diabetic nephropathy and its mechanism. After transfection of podocytes with si-NC and si-Circ_0015756, they were then exposed to normal glucose and high glucose (HG). Cell invasion and migration ability were
detected by Transwell and scratch test, while cell proliferation and apoptosis were analyzed by flow cytometry, and apoptosis and anti-apoptotic protein expression were analyzed by Western blotting. Bioinformatics software and gene assay were employed to detect and verify the relationship
between miR-136 and Circ_0015756. Finally, the activation state of NF-κB pathway was analyzed by Western blot. HG treatment induced podocytes injury and suppressed invasion and migration activity, accompanied by increased Circ_0015756 expression. And silencing of Circ_0015756
alleviated cell injury induced by HG treatment, while miR-136 knock down abolished Circ_0015756 silencing’ protective effect. Further, silencing of Circ_0015756 inhibited NF-κB pathways by regulating miR-136. HG environment induced upregulation of Circ_0015756 expression,
while silencing of Circ_0015756 regulated the NF-κB pathway by upregulating miR-136 expression, thus alleviating podocytes injury induced by HG treatment.
Power, Politics, People, and Knowledge
Authors: Williams Johnny E.
Published: June 2023

In an age when many professors, politicians, and everyday people are harassed and threatened for their political views and lifestyles, this presidential address asks that we reflect about people as historical and social actors. It urges us to be resolute in the face of a changing world and generous enough to recognize change is an outcome of people’s actions. As such, can unmake what we the people create. The address contends that it is essential for social scientists to direct our attention to the great struggles and issues of our time in a collaborative effort with everyday people to create a truly beloved community. Consider that most academicians are not in a collaborative mood C. Wright Mills’s poignantly stated: “it is one thing to talk about general problems . . . , and quite another to tell an individual what to do. Most ‘experts’ dodge that question. I do not want to.” This address urges reluctant social scientists to step into struggle for creation of the beloved community. It asks us to consider the contributions of actors and epistemologies of regions in the nation and around the world. Moreover, the address asks that we confront the obstacles fueling our reluctance to engage struggles for liberation.
“It’s Bigger Than Just a Book Challenge”: A Collective Case Study of Educators’ Experiences With Censorship
Authors: Sachdeva Danielle E. , Kimmel Sue C. , Chérres J. Sebastián
Published: June 2023

Background:

Challenges to books are surging across the United States, and books that portray diverse human experiences are particularly targeted. Censorship has deleterious consequences, such as undermining children’s intellectual freedom and influencing educators’ book selections. In a climate of censorship, when educators face the realistic possibility of a challenge, diverse voices may be silenced, and real-world issues avoided. Despite the impact that book challenges have, the experiences of educators who have faced them are understudied.

Purpose:

This study investigates the self-reported experiences of seven educators who have been involved in book challenges within K–12 public schools within the United States. Its goal is to yield new insights about how educators perceive the experience of censorship and what resources they leverage as they defend children’s right to read. It is significant because the lessons learned from these educators may be instructive for novice and veteran teachers and school librarians who are facing censorship—an increasingly likely possibility in contemporary times. It also highlights the range of forms that censorship takes within today’s schools.

Research Design:

This research employs a collective case study design. Seven teachers and school librarians from K–12 public schools across the United States were interviewed about their experiences with book challenges and other forms of censorship. Interview transcripts were qualitatively analyzed using Pierre Bourdieu’s types of cultural capital as a framework. Within-case and cross-case analyses are presented.

Conclusions:

Participants drew from various forms of cultural capital in their efforts to defend children’s intellectual freedom, including their professional ethics, school policies, and institutional knowledge. The study emphasizes the importance of building cultural capital among pre- and in-service educators within university preparation and professional development programs. It also calls on professional groups within education and librarianship to take an organized stand against censorship.
English learners who are blind or visually impaired: A participatory design approach to enhancing fairness and validity for language testing accommodations
Authors: Guzman-Orth Danielle , Steinberg Jonathan , Albee Traci
Published: June 2023

Standardizing accessible test design and development to meet students’ individual access needs is a complex task. The following study provides one approach to accessible test design and development using participatory design methods with school community members. Participatory research provides opportunities to empower collaborators by co-creating knowledge that is useful for assessment development. In this study, teachers of students who are visually impaired, students who are blind or are visually impaired, English language teachers, and test administrators provided feedback at critical stages of the development process to explore the construct validity of English language proficiency (ELP) assessments. Students who are blind or visually impared need to be able to show what they know and can do without impact from construct-irrelevant variance like language acquisition or disability characteristics. Building on our iterative accessible test design, development, and delivery practices, and as part of a large project on English-learner proficiency test accessibility and usability, we collected rich observation and interview data from 17 students who were blind or visually impaired and were enrolled in grades kindergarten through Grade 12. We examined the ratings and item metadata, including assistive technology preferences and interactions, while we used grounded theory approaches to examine qualitative thematic findings. Implications for research and practice are discussed.
Patterns of Adaptive Learning Scales and Achievement Goal Questionnaire 3 × 2: More Different than Similar
Authors: Lopez J. , Johnson C. , Dai L. , Jones M. H. , Nodine M. , Cooper D. , Eckel S.
Published: June 2023

The present study examined the convergent validity between two frequently used achievement goal instruments: Patterns of Adaptive Learning Scales (PALS) and the Achievement Goal Questionnaire 3 × 2 (AGQ 3 × 2). Confirmatory factor analysis and structural equation models tested for relationships both within and across the scales in a sample of undergraduate students ( N = 363). Main findings suggested that the PALS and AGQ 3 × 2 had stronger relationships within their respective instruments then between the scales. The PALS and AGQ 3 × 2 instruments had some similarities between mastery goals, but relationships between the performance goals of these two instruments were weaker or uncorrelated. These findings suggest/highlight the ongoing disparities in the measurement of achievement goal theory. Future research should consider that the PALS and AGQ 3 × 2 goal instrumently likely measure different theoretical constructs.