bluuebunny/crossref_metadata_2025 huggingface dataset:
68 Rapid detection of somatic variants in human leukocyte antigen class 1 genes from solid tumor samples
Authors: Bharanikumar Ramit , Beutner Karl , Khan Aly , Perera Jason
Published: November 2021

Background

Human Leukocyte Antigens (HLA) class 1 proteins are important for recognizing tumor specific mutations (neoantigens) and presenting them to CD8+ T-cells. Somatic mutations in HLA genes can potentially reduce the set of neoantigens available for presentation to T-cells, providing a possible immune escape mechanism for tumors. The presence of mutations in HLA genes may thus affect an individual’s response to Immune Checkpoint Blockade therapy but calling somatic variants in HLA genes is challenging given high degrees of polymorphism and the presence of pseudogenes in HLA loci. Here, we present a rapid, modular algorithm to detect somatic variants in HLA class 1 genes from next-generation sequencing data.

Methods

Our method takes as input matched tumor and normal sequencing (BAM) files and a patient‘s HLA type. Our first step involves mapping and aligning reads to the full-length HLA class 1 genes of an individual patient. Next, we filter reads to minimize sequencing errors and process them to account for potential cross-mapping between genes in the broader HLA locus. Our algorithm uses the final set of processed reads from matched tumor and normal sequencing files to call somatic variants. The final set of variants are then provided with a genetic variant annotation that summarizes their functional effect.

Results

We validated the efficacy of our approach using TCGA samples that were previously known to contain somatic HLA mutations. Out of a total of 46 mutations previously characterized from 41 samples, our algorithm detected 43 mutations with the correct functional annotation and did so with a computational run-time that is an order of magnitude faster than the current gold-standard approach. Eight of these mutations were previously validated using PacBio long-read sequencing, and all of these validated mutations were detected by our method. Additionally, we analyzed transcriptomic data in samples containing nonsense mutations and detected a transcriptomic signature in RNA-seq data that corresponded to the Nonsense Mediated Decay pathway.

Conclusions

Our findings show that our algorithm can reliably and rapidly detect somatic mutations in HLA class 1 classical genes. We leveraged multi-modal TCGA data and modules developed at Tempus to link samples with nonsense mutations to the nonsense mediated decay pathway. This allowed us to posit a possible biological mechanism that could result in increased resistance to immunotherapy because of somatic HLA mutations. Finally, we emphasize that our approach is modular and can be extended to call somatic variants in other non-classical and class 2 HLA genes.
73 Characterization of tumor-infiltrating T-cell repertoire in human cancers
Authors: Harding Taylor , Yang Qidi , Mineo Brittany , Malinauskas Jenna , Perera Jason , Beutner Karl , Lau Denise , Khan Aly
Published: November 2021

Background

TCR and BCR repertoire profiling is a promising technique that can provide a clinically useful window into the complex interactions between tumor cells and infiltrating lymphocytes. Despite recent advances in repertoire sequencing methods, the characterization of tumor-infiltrating T-cell repertoires has been limited to small sample sizes due to technical and material constraints. In this study, we constructed a large multidimensional database of repertoire data covering a diverse landscape of HLA genotypes and tumor neoantigens from routine clinical sequencing. We present a descriptive summary of repertoire profiles derived from tens of thousands of tumor samples from over fifty different cancer cohorts and characterize the associations between T-cell repertoires and various clinical and molecular features.

Methods

To enrich immune receptor transcripts detected by the Tempus RNA-sequencing workflow, hybrid capture probes tiling TCR and BCR genes were used. Repertoire profiling reads were aligned, assembled, and annotated against IMGT reference sequences. Repertoires are profiled as a component of Tempus|xT RNA sequencing and are summarized here for >25 thousand tumor samples from over 50 different cancer cohorts.

Results

We demonstrate that the use of TCR/BCR hybrid capture probes is an effective method for enriching immune receptor transcripts in RNA-sequencing data without interfering with downstream transcriptomic analysis. These repertoires were profiled as part of a larger, multimodal DNA/RNA-sequencing pipeline that quantifies a variety of tumor clinical and molecular features. We explored the correlation between high-level repertoire metrics like richness (the number of unique receptor clonotypes in a given repertoire) and clonality/evenness (Shannon entropy) against both gene expression-based metrics (i.e. immune cell infiltration estimates, etc.) and mutational patterns (mutational burden and neoantigen load). Finally, we observed that the repertoire clonality of B-cell and T-cell driven cancers frequently exhibits clear monoclonal dominance for the tumor cells’ lymphoid receptors.

Conclusions

TCR/BCR repertoire profiling can be incorporated into high-volume clinical RNA sequencing to generate a diverse multimodal dataset for studying the tumor-immune microenvironment. By creating a large-scale database of TCR/BCR repertoire profiles from a variety of tissue, HLA genotypes, and mutational contexts, we can better resolve the molecular and clinical correlates of cancer with host adaptive immunity.
85 Detection of human angiotensin-converting enzyme 2 receptor (hACE2R) on human cancer cell lines
Authors: Moudgil Tarsem , Fox Bernard , Hu Hong-Ming
Published: November 2021

Background

SARS-CoV-2 infections have delayed administration of treatments for some patients with cancer, increasing the number of avoidable deaths. However, we hypothesized that infection of cancer cells with SARS-CoV-2 might increase the immunogenicity of those cancer cells. Here we sought to determine whether non-small cell lung cancer (NSCLC) and head and neck squamous cell cancer (HNSCC) cell lines could be a potential target of SARS-CoV-2, which binds and infects host cells via interactions between the viral spike glycoprotein and the human angiotensin-converting enzyme 2 receptor (hACE2) receptor. Through an institutional research tissue protocol, our lab has established a panel of cancer cell lines of various histologies. Here we set out to identify whether HNSCC and NSCLC cell lines expressed the hACE2R. We also investigated the expression of neuropilin-1, a molecule reported to facilitate SARS-CoV-2 cell entry.

Methods

Established cell lines were phenotyped by flow cytometric analysis utilizing the anti-hACE2R antibody from Novus Biologicals. Cell lines were also stained with mIgG1 and anti-CD3 antibodies as negative staining controls.

Results

We identified that three of eight NSCLC cell lines expressed the hACE2R and two of these had strong expression of neuropilin-1. Evaluation of HNSCC cell lines identified seven of seven cell lines expressed detectable levels of hACE2R but only one of seven HNSCC celllines expressed substantial levels of neuropilin-1. Preliminary evaluation of a renal cell carcinoma (RCC) cell line revealed strong staining for hACE2R.

Conclusions

Our study found that a majority of HNSCC cell lines (100% n=7) and approximately a third of the NSCLC cell lines (37.5%, n=8) tested express the hACE2R. Some cell lines express both hACE2R and neuropilin-1, potentially increasing their susceptibility for infection with SARS-C0V-2. While these studies were performed with cultured cell lines that may have modulated expression of hACE2R, it is possible that in vivo these tumors express the ACE2R and could serve as a target and possible reservoir for SARS-CoV-2.

Acknowledgements

Support

The Chiles foundation, Nancy Lematta
90 Unbiased proteomic profiling leads to the discovery of a novel non-invasive blood-based protein panel with significant positive predictive value in pancreatic and colorectal cancers
Authors: Beeler Kristina , Bruderer Roland , Tognetti Marco , Sklodowski Kamil , Mueller Sebastian , Kamber Dominique , Reiter Lukas
Published: November 2021

Background

Mass spectrometry-based discovery proteomics has recently emerged as a high-throughput method for the proteomic profiling in biofluid samples from large clinical and population screening cohorts. Despite this progress, a significant fraction of the plasma proteome is currently not covered by state-of-the-art discovery approaches and therefore not accessible for biomarker discovery. To close this analytical gap, we present a novel workflow combining automated plasma depletion and FAIMS-DIA-MS to bridge both sensitivity and scalability. We demonstrate the applicability of this workflow to support biomarker discovery and subject stratification in precision oncology in a case-control cohort.

Methods

The plasma samples were depleted in 96-well format using an automated MARS-14 depletion system. The depleted samples were processed to tryptic peptides and analyzed using a Thermo Scientific Orbitrap Exploris 480 equipped with a FAIMS Pro device. Data processing and analysis were performed using Biognosys’ SpectroMine and Spectronaut software.

Results

Using the unbiased discovery workflow, we investigated a cohort comprising of 180 plasma samples from healthy donors and subjects diagnosed with pancreatic, breast, prostate, colorectal and lung (NSCLC) cancer at either early or late stage of the disease. Overall, the optimized FAIMS-DIA-MS quantified 2,741 proteins across all samples and 1,849 proteins on average per sample measurement. Based on estimated plasma protein concentrations (Human Protein Atlas), quantified proteins span across 8 orders of magnitude, down to single digit pg/mL. Within this dynamic range, we could interrogate the tissue leakage proteome, interleukins and signaling proteins. Using classification algorithms, we were able to select candidates to build protein panels which provide significant positive predictive values associated with different disease stages, especially in the sub-cohorts for pancreatic and colorectal cancer.

Conclusions

We demonstrate the capabilities of a novel discovery workflow for deep, quantitative profiling of plasma samples at large scale, providing a rich proteomic resource for precision oncology.
223 Potent inhibition of PI3Kδ promotes enhanced T cell stemness and mitochondrial fitness
Authors: RIvera Guillermo Rangel , Dwyer Connor , Knochelmann Hannah , Smith Aubrey , Cole Anna , Wyatt Megan , Ware Brandon , Paulos Chrystal
Published: November 2021

Background

Durable responses have been observed with adoptive T cell therapy (ACT) in chemotherapy and immunotherapy refractory patients. However, current T cell products do not always lead to therapeutic responses. Therapy failure has been attributed to terminally-differentiated T cell profiles, diminished host engraftment and poor mitochondrial metabolism. T cell activation and a switch towards glycolysis is regulated by signals downstream of the PI3K signaling pathway. We hypothesized that by inhibiting the T cell specific PI3Kδ subunit, that we would prevent overt T cell differentiation, enhance mitochondrial metabolism and improve anti-tumor immunity of adoptively transferred T cells.

Methods

To test this, we primed melanoma-specific CD8+ pmel-1 T cells in the presence of increasing concentrations of CAL-101, a PI3Kδ specific inhibitor, and infused them into B16F10 tumor-bearing mice, following non-myeloablative total body irradiation. In vitro we tested how PI3Kδ inhibition altered T cell stemness features by flow cytometry and RNA sequencing. Further, we tested the ability of PI3Kδ inhibited T cells to survive against antigen rechallenge, and assessed how mitochondrial phenotypes changed using dyes indicating mass, membrane potential and reactive oxygen species. Moreover, we tested how real time mitochondrial respiration was changed with PI3Kδ inhibition via seahorse.

Results

Potent inhibition of PI3Kδ in vitro enhanced tumor immunity and survival in a dose dependent manner. High doses of CAL-101 enriched T cells with phenotypic and transcriptional signatures of stemness. We found that CAL-101 decreased glucose uptake and increased mitochondrial mass and membrane potential while reducing mitochondrial reactive oxygen species. Potent inhibition of PI3Kδ enhanced mitochondrial respiration, however gene expression of fatty acid oxidation was not enriched, suggesting an alternative pathway involved in the enhanced spare respiratory capacity of CAL-101 treated T cells.

Conclusions

These findings indicate that blocking PI3Kδ is sufficient to mediate lasting tumor immunity of adoptively transferred T cells by preserving stemness features and improving mitochondrial fitness. Our data suggest that addition of CAL-101 to ACT expansion protocols could greatly improve responses to solid tumors by rewiring T cell stemness and promoting mitochondrial fitness.

Acknowledgements

We would like to thank all the researchers and clinicians leading the way in translating immunological principles into effective therapies, as well as the patients whose support is integral for the furthering of medicine.

Ethics Approval

All animal procedures performed at the Medical University of South Carolina or Emory University were approved by each university’s Institutional Animal Care & Use Committee, protocol number 0488 or 201900225, respectively
224 M2 macrophage-mediated immune suppression of chimeric antigen receptor T cells via PD-L1 signaling in prostate cancer
Authors: Yamaguchi Yukiko , Gibson Jackson , Ou Kevin , Priceman Saul
Published: November 2021

Background

The immune suppressive tumor microenvironment (TME) that inhibits T cell infiltration, survival, and anti-tumor activity has posed a major challenge for developing effective immunotherapies for solid tumors. Chimeric antigen receptor T cell therapy has shown unprecedented clinical response in treating patients with hematological malignancies, and intense investigation is underway to achieve similar responses with solid tumors. Immunologically cold tumors, including prostate cancers, are often infiltrated with abundant macrophages, and infiltration of M2 macrophages correlates with metastasis and poor prognosis.

Methods

To model this in vitro, we utilized a novel co-culture system with tumor cells, prostate stem cell antigen (PSCA)-directed CAR T cells, and polarized macrophages. To investigate the TME in vivo, we took advantage of ”humanized” MISTRG mice, which are immunocompromised mice with knocked-in human genes that support human hematopoiesis and efficient tumor-infiltration of myeloid cell populations. Humanized MISTRG mice were intratibially engrafted with LAPC9 tumor cells to model bone metastatic disease.

Results

We observed significant hampering of PSCA-CAR T cell activity in vitro with the presence of M2 macrophages, but not M1 macrophages, coinciding with a robust induction of PD-L1 in both tumor cells and macrophages. We also observed PD-L1 expression in tumor-associated macrophages infiltrating tumors following PSCA-CAR T cell therapy in the humanized mice. Anti-PD-L1 monoclonal antibodies in combination with CAR-T cell therapy altered phenotype and survival of M2 macrophages, resulting in improved anti-tumor activity of PSCA-CAR T cells in the presence of M2 macrophages.

Conclusions

Recently, immune checkpoint (IC) blockade (ICB) has been utilized in combination with chimeric antigen receptor (CAR) T cell therapy, with the notion that induction of immune responses with CAR T cells may instigate checkpoint pathways in immunologically cold tumors that would otherwise not respond to ICB. This study gives insights to a mechanism by which CAR T cells and ICB work in synergy to modulate immune landscape of immunologically cold tumors, and our ongoing studies will continue to elucidate the TME-mediated immunosuppression of CAR T cell therapy.
299 Broad T antigen-specific CD8+ T cell repertoire is associated with response to PD-1 blockade in virus positive merkel cell carcinoma
Authors: Hansen Ulla , Church Candice , Bentzen Amalie , Fling Steven , Ramchurren Nirasha , Topalian Suzanne , Nghiem Paul , Hadrup Sine
Published: November 2021

Background

Merkel cell carcinoma (MCC) is an aggressive human skin cancer primarily induced by Merkel Cell Polyomavirus (MCPyV) driven by expression of the oncogenic T antigens (T-Ags): Large T and Small T antigen. Checkpoint inhibition therapy blocking the programmed cell death protein-1 (PD-1) pathway has proven effective with a clinical response rate up to 58%,1 highlighting the critical role of immune surveillance for tumor control. Yet, evidence for the impact of T-Ag-specific T cells following immunotherapy is still limited.

Methods

Potential CD8+ T cell epitopes derived from the T-Ags and the Viral capsid protein 1 (VP1) were predicted with netMHCpan 4.0 as 9- and 10-mer peptides with a rank score <2 for binding to 33 different HLA class I types. Peripheral blood mononuclear cells (PBMC) were obtained from 24 MCPyV+ MCC patients prior and post anti-PD-1 therapy initiation (CITN-09/Keynote-017). T cell recognition of the MCPyV-derived peptides during therapy was evaluated using the high-throughput technology of DNA barcode labeled pMHC multimers. Phenotypic characteristics of multimer-binding T cells were evaluated for selected patients.

Results

Across all patients, 40 T-Ag-specific CD8+ T-cell populations were detected recognizing 31 epitopes restriction to 14 different HLA class I types. T-Ag-specific CD8+ T cells were detected in responders (complete and partial response, n=17) during therapy with a trend of increased number of responses observed after therapy initiation. Whereas only a single T-Ag-specific population was detectable in non-responders (stable and progressive disease, n=7). Moreover, the T cell repertoire after therapy initiation was significantly increased in the responder group compared to non-responder with the T-Ag-specific T cells showing an activated effector memory phenotype.

Conclusions

The current study indicates that the T-Ag-specific T cells are associated with clinical benefit to checkpoint inhibitor therapy. Furthermore, the broad identification of novel T-Ag-derived T cell epitopes could potentially facilitate the use of targeted T cell therapy to enhance T cell recognition and clearance of MCC in combination with checkpoint inhibition.

Acknowledgements

Supported by the Cancer Immunotherapy Trials Network (CITN)

Reference

Nghiem P, Bhatia S, Lipson E. Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma. J Immunother cancer 2021;9:e002478.
322 Melanoma-intrinsic hypoxia-inducible factor-1α results in diminished T cell accumulation within the tumor microenvironment
Authors: Higgs Emily , Gajewski Thomas , Trujillo Jonathan
Published: November 2021

Background

The hypoxia-inducible factor (HIF) system, consisting of the transcription factors HIF-1α and HIF-2α, mediates cellular adaptation to hypoxia, and can promote cancer progression, invasion, and metastasis. HIF pathway activation in the tumor microenvironment has been implicated in cancer immune evasion; however, a direct causal role for tumor cell-intrinsic HIF-1α and HIF-2α activation in mediating T cell exclusion and cancer cell resistance to immune checkpoint inhibitor therapy has not been demonstrated.

Methods

We performed gene expression analysis of melanoma tumors in the Cancer Genome Atlas (TCGA) data set to determine whether increased HIF-1α pathway activation correlated with reduced T cell-based inflammation. The magnitude of HIF-1α pathway activation across melanoma samples was determined by applying a quantitative scoring system on the expression of a melanocyte-specific hypoxia-induced, HIF-1α-target gene signature consisting of 81 genes. The Pearson correlation test was used to compare the HIF-1α activation score and our 160-gene T-cell-inflamed gene signature. To determine the impact of cancer cell-intrinsic HIF-1α or HIF-2α activation on the endogenous anti-tumor T cell response, we developed an inducible autochthonous mouse melanoma model driven by BRAFV600E expression and PTEN-deletion, with or without inducible expression of either a stabilized variant of HIF-1α or HIF-2α. These murine tumor models are being used to determine the impact of cancer cell-intrinsic HIF-1α or HIF-2α activation on tumor sensitivity to anti-PD-1/PD-L1 and anti-CTLA-4 treatment.

Results

Gene expression analysis of human melanomas in the TCGA demonstrated a statistically significant inverse correlation between the HIF-1α activation score and T cell-inflammation score. Braf/PTEN murine melanomas with and without stabilized HIF-1α expression developed with comparable tumor onset and growth kinetics. Multiparameter immunofluorescence staining of melanoma tissue revealed a significant decrease in tumor-infiltrating T cells within Braf/PTEN melanoma tumors expressing stabilized HIF-1α compared to control Braf/PTEN melanomas.

Conclusions

Our data demonstrate that tumor-cell intrinsic HIF-1α activation leads to diminished T cell accumulation within the tumor microenvironment, which has implications for cancer immunotherapy. The mechanism of this effect is being elucidated. These novel murine models will help elucidate the roles of cancer cell-intrinsic HIF-1α and HIF-2α activation in modulating the anti-tumor T cell response, providing mechanistic insight that will inform the evaluation of novel selective HIF inhibitors, which are showing promising anti-tumor activity in clinical trials in patients with advanced solid tumors.
382 The synthetic long peptide cancer vaccine UV1 in combination with ipilimumab induces a CD4+ Th1 anti-hTERT immune response and an inflammatory tumor microenvironment in patients with melanoma
Authors: Ellingsen Espen , Kerzeli Iliana , Anzar Irantzu , Mensali Nadia , Clancy Trevor , Mangsbo Sara , Aamdal Steinar , Aamdal Elin , Guren Tormod , Inderberg-Suso Else-Marit , Hovig Eivind , Gaudernack Gustav
Published: November 2021

Background

Checkpoint inhibitors (CPIs) have revolutionized the treatment of malignant melanoma. Although melanoma patients may experience deep and durable clinical responses to CPI treatment, the majority develop disease progression requiring additional therapy. Combining CPIs with therapeutic cancer vaccines may augment the anti-tumor immune response and thus improve clinical outcomes. UV1 is a therapeutic cancer vaccine based on synthetic antigens derived from the tumor-associated antigen telomerase reverse transcriptase (hTERT). hTERT is activated in 85–90% of all cancers and leads to replication of telomeric DNA, an essential mechanism for increased proliferation, immortality, and invasiveness of cancer cells. In this phase I/IIa study combining UV1 with ipilimumab in patients with melanoma (NCT02275416), we hypothesized that UV1 and ipilimumab might provide synergy in the expansion of vaccine-induced T cells. Furthermore, an augmented CD4+ Th1 immune response targeting a shared tumor antigen may increase T cell infiltration in the tumor microenvironment, promoting immune-mediated cancer cell death.

Methods

The immune response dynamics were assessed by longitudinal immunomonitoring for up to 5 years using a standard proliferation assay. The phenotype and functionality of vaccine-induced T cells were assessed by patient-derived T cell cloning and subsequent in vitro characterization by flow cytometry, peptide stimulation, and cytokine release assays. On available biopsies harvested at baseline and 12 weeks after treatment initiation, the tumor microenvironment was assessed based on whole-exome sequencing, RNA sequencing, and immunohistochemistry.

Results

Twelve patients with metastatic melanoma were enrolled in the study and received up to 9 vaccine doses over a 20-week period. A persistent (up to 5 years) vaccine-induced immune responses were demonstrated in 91% of evaluable patients (10/11). Vaccine-specific T cell clones were polyfunctional CD4+ Th1 cells, producing both IFN-γ and TNF-α upon in vitro peptide stimulation. Differential gene expression analysis and immunohistochemical characterization of biopsies at baseline and 12 weeks showed induction of an inflammatory ”hot” tumor microenvironment in clinical responders with available paired biopsies.

Conclusions

UV1 in combination with ipilimumab leads to robust and long-lasting CD4+ Th1 anti-hTERT immune responses sculpting the local tumor microenvironment.

Trial Registration

NCT02275416

Ethics Approval

The study was approved by Regional Ethical Committee South East (ID number 25 165). The patients provided their written informed consent to participate in the study.
Solvatochromic and pH Switch Properties of a D–π–A Dye with benzo[b]thiophene as Donor Moiety
Authors: Feng Lili , Wang Pengyu , Yang Hansen , Chen Zhuo , Bo Shuhui
Published: November 2021

A charge transfer dye with the D–[Formula: see text]–A structure was synthesized by Pd catalyzed Hartwig–Buchwald coupling and Knoevenagel condensation reaction, using N, N-dihexylbenzo[b]thiophen-6-amine as donor and 2-(3-cyano-4, 5, 5-trimethylfuran-2 (5H)-ylidene)malononitrile (TCF) as acceptor. The solvatochromic and pH switch properties of the as-synthesized dye were investigated through UV-vis absorption and fluorescence emission spectra. A positive solvatochromism of the dye in different polar solvents was observed along with a visible color change of the solution. By adding acid/base into the DMSO solution of the dye, the color as well as the absorption and emission spectra of the solution exhibited outstanding characteristics of pH switch.
STAT1-Induced Upregulation lncRNA LINC00958 Accelerates the Epithelial Ovarian Cancer Tumorigenesis by Regulating Wnt/β-Catenin Signaling
Authors: Xie Min , Fu Qi , Wang Pin-pin , Cui Yu-lan
Published: November 2021

Background. Growing studies have demonstrated that long noncoding RNAs (lncRNAs) play important roles in tumor progression. In this study, we aimed to explore the potential roles of lncRNA LINC00958 (LINC00958) and its biological functions in epithelial ovarian cancer (EOC). Methods. The expression of LINC00958 in 11 cases of EOC and adjacent nontumor specimens and five cell lines was detected by qRT-PCR. CCK-8, colony formation, and flow cytometry assays were conducted to study the cell viabilities of EOC cells. Wound scratch and transwell analyses were carried out for the examination of cell invasion and migration of EOC cells. The targeting associations between LINC00958 and STAT1 were demonstrated by ChIP analyses combined with luciferase reporter assays. The related proteins of Wnt/β-catenin signaling were determined using RT-PCR. Results. Higher levels of LINC00958 were observed in EOC tissues and cell lines. Our data also revealed that high LINC00958 expression was partly induced by STAT1. Functionally, knockdown of LINC00958 suppressed the proliferation, migration, and invasion of EOC cells. Mechanistic investigation showed that the inhibitory effect of LINC00958 knockdown on EOC cells was mediated by the Wnt/β-catenin signaling. Conclusion. Our findings suggested that STAT1-induced overexpression of LINC00958 promoted EOC progression by modulating Wnt/β-catenin signaling.
Differences in the Values of the Senior Management Team, Antirisk Ability, and Innovation Performance by the Data-Driven Approach: Evidence from 841 Listed Companies in China
Authors: Tong Guangyin
Published: November 2021

This study explores the mechanism of corporate antirisk capabilities on corporate innovation performance by using a data-driven method. The data are from China’s Shanghai and Shenzhen A-share listed companies from 2013 to 2018. The value differences between the senior management team’s ability to resist risk and innovation performance are discussed. The results show that the antirisk ability of an enterprise will improve the efficiency of the utilization of enterprise resources and promote the formation of competitive advantage so that enterprises have a more stable internal and external environment, so as to improve the innovation performance of the enterprise. Risk capability improves corporate innovation performance; from the perspective of the value difference of the senior management team, a smaller value difference has a more significant effect on enhancing the enterprise’s antirisk ability and improving corporate innovation performance than a larger value difference. While improving their own antirisk capabilities, companies should further promote and improve the consistency of senior management team values, thereby improving corporate innovation performance.
Assessment of Energy Potential and Benefit under the Ground Source Heat Pump Air Conditioning System in Anqing Area of Eastern China
Authors: Zhang Qing , Li Yunfeng , Hua Jian , Niu Xiaonan , Hou Lili , Chen Zongfang , Ge Weiya
Published: November 2021

Now ground source heat pump is a more efficient way to develop and utilize shallow geothermal energy because it is clean and environmentally friendly and has a relatively low energy cost. In order to optimize the planning layout and geographical space development in the eastern new town of Anqing city, which can realize the transformation and upgrading of real space and urban sustainable development, the exploration for shallow geothermal energy will be carried out in this area, so as to find out the comprehensive thermophysical parameters of the shallow rock-soil body and the heat transfer capacity of the vertical heat exchanger, etc. This paper takes the CBD in the eastern new town of Anqing as an example to provide the basis for the feasibility construction of the ground source heat pump project in the study area and evaluate the economic and environmental benefits of the expected project. According to the simulation test data of 5 working conditions of 4 geothermal exploration holes in the study area, we can clearly know that the energy cost per square meter of the ground source heat pump is 11.8 yuan for a building of one hundred thousand square meters in which the heat removal power is expected to be 9481 kW in summer and 3070 kW in winter. And the annual emission of carbon dioxide, sulfur dioxide, nitrogen oxides, suspended dust, and other air pollutants to the atmosphere can be reduced by 1442.5 t, and the solid waste ash and slag can be reduced by 59.7 t. The annual environmental treatment cost will be saved by 166000 yuan.
The Ocular Surface Characteristics in Prostate Cancer Patients Treated with Androgen Deprivation Therapy
Authors: Li Weina , Li Xiaofeng , Cui Feilun , Xu Zhipeng , Dong Nuo , Li Cheng
Published: November 2021

Background.To investigate the association of long-term androgen deprivation therapy (ADT) with ocular surface characteristics in prostate cancer patients. Methods. A total of 30 male prostate cancer patients who received ADT were selected. All candidates were scored using the Ocular Surface Disease Index (OSDI) and subsequently divided into two groups containing 9 symptomatic patients (scores >12) and 21 asymptomatic patients (

scores
≤
12

). Another 20 healthy age-matched males were selected as the control group. Each candidate was assessed with respect to eyelid margin abnormality, tear film break-up time (NI-BUT), tear meniscus height (TMH), meiboscore, meibum expressibility, and demodex infection. Results. The NI-BUT in the ADT group was significantly shorter than that in the control group. The scores for OSDI, eyelid margin abnormality, meibum expressibility, and meiboscores were significantly higher in the ADT group (

P
<
0.05

). Moreover, the NI-BUT in the symptomatic ADT group was significantly shorter than that in the asymptomatic ADT group (

P
<
0.05

). The meiboscores and meibum expressibility score in the symptomatic ADT group were significantly higher than those in the asymptomatic ADT group (

P
<
0.05

). The presence of demodex in the symptomatic ADT group was also higher than that in the asymptomatic ADT group (

P
<
0.05

).The length of time that patients had been taking ADT was positively correlated with meiboscores and negatively correlated with NI-BUT. Conclusion. Androgen levels were associated with significant changes in relative meibomian gland function. Subjective symptoms, such as dryness and foreign body sensation, were more obvious in prostate cancer patients receiving ADT, which may be caused by MGD and demodex infection. It’s recommended that more attention be paid to the ocular surface in prostate cancer patients taking ADT by performing examination of NI-BUT and meibomian gland morphology and function with a view to providing more comprehensive prevention and treatment protocols.
Treatment of Lupus Nephritis from Iranian Traditional Medicine and Modern Medicine Points of View: A Comparative Study
Authors: Vahedi-Mazdabadi Yasaman , Saeedi Mina
Published: November 2021

Objective. Nephritis or kidney inflammation is characterized as one of the most common renal disorders leading to serious damage to the kidneys. Nephritis, especially lupus nephritis (LN), has remained as the main cause of chronic renal failure which needs serious therapeutic approaches such as dialysis and kidney transplant. Heredity, infection, high blood pressure, inflammatory diseases such as lupus erythematosus and inflammatory bowel disease, and drug-related side effects are known as the main causes of the disease. According to Iranian traditional medicine (ITM), infectious diseases and fever are the main reasons of nephritis, which is called “Varam-e-Kolye” (VK). Results. There are various plant-based remedies recommended by ITM for the treatment of nephritis, as discussed herein, comparing with those available in the modern medicine. There is no definite cure for the treatment of nephritis, and immunosuppressive drugs such as corticosteroids and nonsteroidal anti-inflammatory drugs, antibiotics, diuretics, analgesics, and finally dialysis and kidney transplantation are usually used. Based on the efficacy of medicinal plants, jujube (Ziziphus jujuba), almond (Prunus amygdalus), pumpkin seeds (Cucurbita pepo), purslane (Portulaca oleracea), and fig (Ficus carica) were found to be effective for the treatment of kidney inflammation in ITM. Conclusion. Considering the fact that there is no efficient strategy for the treatment of nephritis, use of herbal medicine, particularly based on the fruits or nuts that have been safely used for several years can be considered as a versatile supplement along with other therapeutic methods.
A Network‐Based Approach to Study Returns Synchronization of Stocks: The Case of Global Equity Markets
Authors: Lavin Jaime F. , Valle Mauricio A. , Magner Nicolás S.
Published: November 2021

The synchronization in financial markets has increased during the rise of global markets. Nevertheless, global shocks provoke high levels of returns synchronization that jeopardize market stability. Using correlation‐based networks, regressions, and VAR models, we measure and estimate the effect of global synchronization on the world equity markets of North America, Latin America, Europe, Asia, and Oceania between July 2001 and April 2020. We find that our measure of global stock synchronization is dynamic over time, its minimums coincide with significant financial shocks, and it shrinks to its minimum levels, indicating that the returns of global markets are moving in a synchronized way. Also, it is a significant and positive factor of regional synchronization. Regional markets react heterogeneously to global synchronization shocks suggesting both local and global factors are sources of synchronization. Our work helps market participants who need to measure, monitor, and manage the synchronization of returns in a parsimonious, dynamic, and empirically tractable way. Our evidence highlights the necessity of including synchronization as a risk factor to assess the decision‐making criteria of a broad range of market participants ranging from regulators to investors. To policy‐makers, governments, and central banks, our work is a call to incorporate events of high global synchronization into the radar of hazards of the whole market stability.
Effect of 3D Printing Parameters on the Refractive Index, Attenuation Coefficient, and Birefringence of Plastics in Terahertz Range
Authors: Clark Alexander T. , Federici John F. , Gatley Ian
Published: November 2021

The refractive indices, attenuation coefficients, and level of birefringence of various 3D printing plastics may change depending on the printing parameters. Transmission terahertz time‐domain spectroscopy was used to look for such effects in Copolyester (CPE), Nylon, Polycarbonate (PC), Polylactic acid, and Polypropylene. The thickness of each sample was measured using an external reference structure and time‐of‐flight measurements. The parameters varied were printer nozzle size, print layer height, and print orientation. Comparison of these parameters showed that a printer’s nozzle size and print layer height caused no change in real refractive index or attenuation coefficient. A change in printing orientation from vertical to horizontal caused an increase both in real refractive index and in attenuation coefficient. In vertically printed samples, the increase in birefringence was proportional to the increase in layer height and inversely proportional to nozzle size. There was no measurable intrinsic birefringence in the horizontally printed samples. These effects should be taken into account in the design of FDM 3D printed structures that demand tailored refractive indices and attenuation coefficients, while also providing a foundation for nondestructive evaluation of FDM 3D printed objects and structures.
Effects of Continuous Catheterization on Reducing Postoperative Urinary Tract Infection in Cervical Cancer Patients with Double J Stent Placement
Authors: Liu Tengteng , Yao Yuan , Xing Xinwen , Chu Daming
Published: November 2021

This study aims at exploring the effect of continuous catheterization on reducing postoperative urinary tract infection in cervical cancer patients with double J tube placement. To be specific, a retrospective analysis was performed on 120 cases of cervical cancer patients who underwent laparoscopic or open radical hysterectomy in Shengjing Hospital of China Medical University from January to December 2019. They were divided into a persistent group (n = 70) and a short-term group (n = 50) according to indwelling catheter time. The incidence of postoperative complications and the positive rate of bacterial culture in bladder urine and double J tube bacterial culture were compared between the two groups. As a result, it was found that the incidence of postoperative fever and urinary tract infection in the short-term group was significantly higher than that in the persistent group (

P
<
0.05

). There was no significant difference in the incidence of postoperative hematuria, bladder stimulation, and urinary system injury between the two groups. The positive rate of double J tube bacterial culture in both groups was also proved to be higher than that in bladder culture, and the difference was statistically significant (

P
<
0.05

). And in the short-term group (

P
<
0.05

), the difference in the positive rate of bladder culture between the two groups was not statistically significant. To conclude, we found that continuous catheterization can reduce the incidence of postoperative urinary tract infection in cervical cancer patients with double J tube placement, which might be helpful for the treatment of cervical cancer.
Poetizando cidades entre nuvens, palavras e cardumes
Authors: Didonet Candice
Published: November 2021

Este texto apresenta descrições de práticas performativas que mobilizam a percepção das relações entre corpo, natureza e cidade tendo a pesquisa artística como mote. O acionamento de metáforas em acontecimentos poéticos resgata a cidade expandida no corpo e, a arte, como conexão criativa atrelada a processos de sensibilização à realidade.
Physical activity combined with sedentary behaviour in the risk of mortality in older adults
Authors: Galvão Lucas Lima , Silva Rizia Rocha , Tribess Sheilla , Santos Douglas Assis Teles , Junior Jair Sindra Virtuoso
Published: November 2021

OBJECTIVE To examine the effects of physical activity (PA) and sedentary behaviour (SB), in isolation and combination, on all-cause mortality in older adults. METHODS Prospective, population-based cohort study. The data were collected from first wave in 2015 and the follow-up continued until 2020. The sample consisted of 332 older adult people aged ≥ 60 years-old, out of which 59 died. The level of PA and SB was assessed by the International Physical Activity Questionnaire (IPAQ). The older adults were divided into PA categorized as sufficiently active and insufficiently active and into high and low SB. We built four combinations of PA and SB. Also, we used the Cox proportional hazards regression with a 95% confidence interval with hazard ratio estimate so as to verify the mortality risks between PA, SB, and the combinations of PA and SB. RESULTS Insufficiently active individuals had higher risks of mortality compared to sufficiently active people. We observed no associations between SB and mortality separately; however, when evaluated in a combined way, insufficiently active individuals and with a high SB time had a higher chance of mortality compared to active individuals with a low SB time. CONCLUSION Our isolated analyses demonstrate that complying with PA recommendations reduces the risk of mortality; however, no association was found between the time of PA exposure with the time of SB. When analysing the combination, being physically inactive and with a long time of SB showed higher mortality rates, with SB being an enhancer of this risk. The results of this study show the interdependence of SB for PA performed at moderate to vigorous intensity. The understanding of this interrelation must be considered in the formulation of public health guidelines.
Virtue, Sanctity, and Charity of the Royal Women of Fez
Authors: Boloix-Gallardo Bárbara
Published: November 2021

The history of the Banū Marīn of the kingdom of Fez (seventh–ninth/thirteenth–fifteenth centuries) cannot and should not be reconstructed without a gender perspective which gives the women of this dynasty a place within its historic discourse. They played a key role in the political and religious legitimacy of the rulers, as reflected by the Banū Marīn historiography which, mirroring the idiosyncrasy of medieval Berber societies, afforded its women a visible space. However, as it was always subject to the clear interests of male political-religious legitimacy, this space for visibilisation is worthy of analysis. This study examines the different profoundly religious behaviour and capabilities which the chronicles assigned to different royal Merinid women, as related in the various anecdotes transmitted in their pages. Additional analysis is carried out on how these model characterisations aimed to increase the aura of spirituality of the amīrs, influenced by their close relationship and everyday contact with these women.
Church, State, and Pluralistic Society
Authors: Nikolajsen Jeppe Bach
Published: November 2021

This article demonstrates that Lutheran teaching on the two regiments can be drawn in different directions and how it was drawn in a particular direction for centuries so that it could provide a theoretical framework for mono-confessional Lutheran societies. It argues that the Lutheran two regiments theory can be developed along a different path, regaining some emphases in Luther’s early reflections: it can thereby contribute to an improved understanding of the role not only of the church but also of the state. While a number of Lutheran theologians believe that Lutheran teaching on the two regiments is particularly difficult to apply today, with some even contending that it should simply be abandoned, this article argues that Lutheran teaching on the two regiments could present a potential for a relevant understanding of the relationship between church, state, and society, and its ethical implications in a contemporary pluralistic society.
What We Talk About When We Talk About Early Release in International Criminal Law: The Sui Generis Nature of the Reduction of Sentence Under the Rome Statute
Authors: Fernández-Pacheco Estrada Cristina
Published: November 2021

Early release has been regularly granted by the ad hoc tribunals for over 20 years. However, it could be argued that some issues still remain contentious. In fact, in May 2020, the Practice Direction ruling early release in the Mechanism of the International Criminal Tribunals was amended. This was intended to clarify key matters, such as the time needed to be served before early release, the possibility of imposing conditions upon those released, and the unappealable character of the resulting decision. At a glance, it could be argued that the International Criminal Court is better equipped to confront the many challenges posed by early release. This is owing to its detailed regulation, which may consequently lead to a more reasoned and solid case law. After comparatively examining ten features key to the application of early release, however, this paper argues that the ultimate problem lies within the nature generally conferred to early release in the Rome Statute.
‘Jugendbewegung’: Gerhard Scholem as a Figure of the German Avant-Garde
Authors: Engel Amir
Published: November 2021

The purpose of this essay is to examine one of Gershom Scholem’s most obscure undertakings, a proto-Dadaist and antiwar text that he published, together with a few friends, during the first year of World War One. As is shown, this project has drawn heavily from the work of one of the leading avant-garde poets, later among the founding members of the Dada movement in Zurich, Hugo Ball. Discussed side by side, the works of Gershom Scholem and Hugo Ball offer a unique view onto the anti-war sentiment and the need for experimental language in an attempt to express a disdain so profound and fundamental that words and sentences seem unable to capture.
Research Trends in Science and Mathematics Education in South Korea 2014–2018: A Cross-Disciplinary Analysis of Publications in Selected Local Journals
Authors: Park Wonyong , Kim Doy , Kang Da Yeon
Published: November 2021

Although science education and mathematics education share many characteristics as neighboring research disciplines, comparisons between the two research fields in the literature have rarely been made. In this study, we examine the two fields’ similarities and differences in the local context of South Korea by analyzing 2,426 research articles published in 15 selected local journals from both fields. The analysis revealed interesting commonalities and divergences across the two fields, suggesting a high degree of similarity in the distribution of research topics across the two fields. Nevertheless, some topics were more frequently studied in one field than the other. Based on the results, we suggest that understanding the ongoing research agendas and aims of adjacent disciplines such as mathematics education will be beneficial to the science education community by allowing self-reflection and facilitating interdisciplinary communication and collaboration. Several potential ways in which the two disciplines can cross-fertilize are discussed.