bluuebunny/crossref_metadata_2025 huggingface dataset:
Super-Resolution and Large Depth of Field Model for Optical Microscope Imaging
Authors: Zheng Ruo-Peng , Liu Shu-Bin , Li Lei
Published: December 2021

Due to the limitation of numerical aperture (NA) in a microscope, it is very difficult to obtain a clear image of the specimen with a large depth of field (DOF). We propose a deep learning network model to simultaneously improve the imaging resolution and DOF of optical microscopes. The proposed M-Deblurgan consists of three parts: (i) a deblurring module equipped with an encoder-decoder network for feature extraction, (ii) an optimal approximation module to reduce the error propagation between the two tasks, and (iii) an SR module to super-resolve the image from the output of the optimal approximation module. The experimental results show that the proposed network model reaches the optimal result. The peak signal-to-noise ratio (PSNR) of the method can reach 37.5326, and the structural similarity (SSIM) can reach 0.9551 in the experimental dataset. The method can also be used in other potential applications, such as microscopes, mobile cameras, and telescopes.
Identification of a Novel PPAR Signature for Predicting Prognosis, Immune Microenvironment, and Chemotherapy Response in Bladder Cancer
Authors: Zhu Ke , Deng Wen , Deng Hui , Liu Xiaoqiang , Wang Gongxian , Fu Bin
Published: December 2021

Background. Mounting evidence has confirmed that peroxisome proliferator-activated receptors (PPARs) played a crucial role in the development and progression of bladder cancer (BLCA). The purpose of this study is to comprehensively investigate the function and prognostic value of PPAR-targeted genes in BLCA. Methods. The RNA sequencing data and clinical information of BLCA patients were acquired from The Cancer Genome Atlas (TCGA). The differentially expressed PPAR-targeted genes were investigated. Cox analysis and least absolute shrinkage and selection operator (LASSO) analysis were performed for screening prognostic PPAR-targeted genes and constructing the prognostic PPAR signature and then validated by GSE13507 cohort and GSE32894 cohort. A nomogram was constructed to predict the outcomes of BLCA patients in combination with PPAR signature and clinical factors. Gene set enrichment analysis (GSEA) and immune cell infiltration were implemented to explore the molecular characteristics of the signature. The Genomics of Drug Sensitivity in Cancer (GDSC) database was used to predict the chemotherapy responses of the prognostic signature. The candidate small molecule drugs targeting PPAR-targeted genes were screened by the CMAP database. Results. We constructed and validated the prognostic signature comprising of 4 PPAR-targeted genes (CPT1B, CALR, AHNAK, and FADS2), which was an independent prognostic biomarker in BLCA patients. A nomogram based on the signature and clinical factors was established in the TCGA set, and the calibration plots displayed the excellent predictive capacity. GSEA analysis indicated that PPAR signature was implicated in multiple oncogenic signaling pathways and correlated with tumor immune cell infiltration. Patients in the high-risk groups showed greater sensitivity to chemotherapy than those in the low-risk groups. Moreover, 11 candidate small molecule drugs were identified for the treatment of BLCA. Conclusion. We constructed and validated a novel PPAR signature, which showed the excellent performance in predicting prognosis and chemotherapy sensitivity of BLCA patients.
Familial Hemophagocytic Lymphohistiocytosis Secondary to PRF1 Mutation
Authors: Alfaraidi Albaraa T. , Alqarni Abdulaziz A. , Aqeel Mohammed T. , Albalawi Turki A. , Hejazi Ahmed S.
Published: December 2021

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that causes systemic inflammation which can progress to multiorgan failure and death. Symptoms and signs commonly seen in HLH include high fever, hepatosplenomegaly, pancytopenia, and hypertriglyceridemia. This report describes the 8-month clinical course of a 17-year-old male with G6PD deficiency who presented with intermittent high fever of unknown origin for 8 months accompanied by pancytopenia and bilateral lower limb weakness. A pathogenic homozygous missense mutation (c.1081A > T p.(Arg361Trp)) in the PRF1 gene was detected by whole exome sequencing (WES). The brain and the whole spine MRI showed leptomeningeal enhancement at different levels involving both the brain and the spine. Therefore, a diagnosis of familial HLH type 2 with CNS involvement was confirmed. Accordingly, treatment with dexamethasone, cyclosporin, and etoposide in addition to intrathecal methotrexate and hydrocortisone was given. The patient showed a dramatic response with significant neurological improvement of the bilateral lower limb weakness. Genetic analysis has helped the patient’s family with appropriate genetic counselling. This case highlights the importance of immediate treatment with immunosuppressants and the high clinical suspicion of physicians regarding HLH in areas where consanguinity is common.
Gut Microbiota and Depressive Symptoms at the End of CRT for Rectal Cancer: A Cross-Sectional Pilot Study
Authors: Gonzalez-Mercado Velda J. , Lim Jean , Saligan Leorey N. , Perez Nicole , Rodriguez Carmen , Bernabe Raul , Ozorio Samia , Pedro Elsa , Sepehri Farrah , Aouizerat Brad
Published: December 2021

Background. The role of alterations in gut microbiota composition (termed dysbiosis) has been implicated in the pathobiology of depressive symptoms; however, evidence remains limited. This cross-sectional pilot study is aimed at exploring whether depressive symptom scores changed during neoadjuvant chemotherapy and radiation therapy to treat rectal cancer, and if gut microbial taxa abundances and predicted functional pathways correlate with depressive symptoms at the end of chemotherapy and radiation therapy. Methods. 40 newly diagnosed rectal cancer patients (ages 28-81; 23 males) were assessed for depressive symptoms using the Hamilton Rating Scale for Depression (HAM-D) and provided stool samples for 16S rRNA sequencing. Gut microbiome data were analyzed using QIIME2, and correlations and regression analyses were performed in R. Results. Participants had significantly higher depressive symptoms at the end as compared to before CRT. The relative abundances of Gemella, Bacillales Family XI, Actinomyces, Streptococcus, Lactococcus, Weissella, and Leuconostocaceae were positively correlated (Spearman’s

rho
=
0.42

to 0.32), while Coprobacter, Intestinibacter, Intestimonas, Lachnospiraceae, Phascolarctobacterium, Ruminiclostridium, Ruminococcaceae (UCG-005 and uncultured), Tyzzerella, and Parasutterella (Spearman’s

rho
=
−
0.43
 
to
−
0.31

) were negatively correlated with HAM-D scores. Of the 14 predicted MetaCyc pathways that correlated with depressive symptom scores at the end of CRT, 11 (79%) were associated with biosynthetic pathways. Conclusions. Significant bacterial taxa and predicted functional pathways correlated with depressive symptoms at the end of chemotherapy and radiation therapy for rectal cancer which warrants further examination and replication of our findings.
Joint Channel Allocation and Power Control for Uplink NOMA‐Assisted Multi‐UAV Networks
Authors: Wen Shaojie , Deng Lianbing , Liu Zengliang
Published: December 2021

The explosive growth of data leads to that the traditional wireless networks cannot enable various quality of service (QoS) communication for cellular‐connected multi‐UAV (unmanned aerial vehicle) networks. To overcome this obstacle, we solve the joint optimization problem of channel allocation and power control for uplink NOMA‐assisted multi‐UAV networks. Firstly, we design a mixed integer nonlinear programming framework, where the channel gains are characterized with integral form in time interval and sorted in nondescending order as the priority index of the decoded signal. In order to propose a feasible algorithm, the initial power levels of UAVs are obtained and integrated into the original problem which is reduced to integer programming problem. Then, the UAVs whose channel gain differences satisfy the constraints will be divided into a group to share the same channel, while the initial power levels of UAVs are adjusted to get a more satisfactory initial solution for power control. Combining the solution of channel allocation and the initial power levels, we solve power control problem with asynchronous update mechanism until the power levels of UAVs remain unchanged. Finally, we propose a channel allocation algorithm and a power control algorithm with the asynchronous optimization mechanism, respectively. Simulation results show that the proposed algorithms can effectively improve the network performance in terms of the aggregated rate.
Design and Implementation of Intelligent Educational Administration System Using Fuzzy Clustering Algorithm
Authors: Liu Fang
Published: December 2021

The present work aims to solve the problems that the traditional educational administration management system has, such as low efficiency in analyzing big data, and the analysis results have low value, which is based on manual rules definition in big data analysis and processing. The work proposes a student achievement prediction model FCM-CF based on Fuzzy C-means (FCM) and Collaborative Filtering (CF). The work also introduces it into the research of educational administration management to construct an intelligent educational administration management system. At the beginning, the FCM-CF model is described in detail. Then, the system requirements and specific design methods are described in detail. Eventually, with the students’ performance prediction as an example, the performance of the system is tested by designed simulation experiments. The result shows that the students’ achievement in study is closely related to their daily study performance such as preparation before class, classroom performance, attendance, extracurricular study, and homework completion. Generally, the examination scores of students are significant to their daily performances. Under the same experimental conditions, the prediction error of the FCM-CF model proposed here is less than 10.8% of that of other algorithms. The model has better prediction performance and is more suitable for the prediction of middle school students’ examination scores in educational administration management system. The innovation of intelligent educational administration management system is that, in addition to the basic information management function, it also has two other functions: students’ performance prediction analysis and teacher evaluation prediction. It can provide data support for improving teaching quality. The research purpose is to provide important technical support for more intelligent educational administration and reduce the loss of human resources in educational administration.
B Cells and Tertiary Lymphoid Structures: Friends or Foes in Cancer Immunotherapy?
Authors: Lauss Martin , Donia Marco , Svane Inge Marie , Jönsson Göran
Published: December 2021

Tumor cells pose a challenge to the adaptive immune system, and its key cell types, T and B cells, have frequently been associated with an improved prognosis. The success of immune checkpoint blockade has confirmed the relevance of T cells. However, the role of B cells is increasingly recognized, and highlighted in this review. Recent data suggest that tumors contain a diverse set of B cells reflecting different developmental states and exerting functions such as antigen presentation, antibody production, and regulatory effects. Further, B cells are frequently located in tertiary lymphoid structures (TLS), which are immune cell niches that sustain an immune response at sites of chronic inflammation. TLSs in tumors display substantial heterogeneity, ranging from cell aggregates to mature structures with an active germinal center. Recent studies have provided insights into initiation, cellular and spatial composition, and function of TLS in a variety of cancer types; however, several critical issues still need to be resolved. Currently, initial reports are discerning the role of TLSs in immunotherapy, with the majority of studies observing TLSs to confer favorable patient outcome. Finally, TLS induction in tumors is evaluated, with the therapeutic aim to reactivate the host immune response.
Differential Survival and Therapy Benefit of Patients with Breast Cancer Are Characterized by Distinct Epithelial and Immune Cell Microenvironments
Authors: Kester Lennart , Seinstra Danielle , van Rossum Annelot G.J. , Vennin Claire , Hoogstraat Marlous , van der Velden Daphne , Opdam Mark , van Werkhoven Erik , Hahn Kerstin , Nederlof Iris , Lips Ester H. , Mandjes Ingrid A.M. , van Leeuwen-Stok A. Elise , Canisius Sander , van Tinteren Harm , Imholz Alex L.T. , Portielje Johanneke E.A. , Bos Monique E.M.M. , Bakker Sandra D. , Rutgers Emiel J. , Horlings Hugo M. , Wesseling Jelle , Voest Emile E. , Wessels Lodewyk F.A. , Kok Marleen , Oosterkamp Hendrika M. , van Oudenaarden Alexander , Linn Sabine C. , van Rheenen Jacco
Published: December 2021

Purpose:

Extensive work in preclinical models has shown that microenvironmental cells influence many aspects of cancer cell behavior, including metastatic potential and their sensitivity to therapeutics. In the human setting, this behavior is mainly correlated with the presence of immune cells. Here, in addition to T cells, B cells, macrophages, and mast cells, we identified the relevance of nonimmune cell types for breast cancer survival and therapy benefit, including fibroblasts, myoepithelial cells, muscle cells, endothelial cells, and seven distinct epithelial cell types.

Experimental Design:

Using single-cell sequencing data, we generated reference profiles for all these cell types. We used these reference profiles in deconvolution algorithms to optimally detangle the cellular composition of more than 3,500 primary breast tumors of patients that were enrolled in the SCAN-B and MATADOR clinical trials, and for which bulk mRNA sequencing data were available.

Results:

This large data set enables us to identify and subsequently validate the cellular composition of microenvironments that distinguish differential survival and treatment benefit for different treatment regimens in patients with primary breast cancer. In addition to immune cells, we have identified that survival and therapy benefit are characterized by various contributions of distinct epithelial cell types.

Conclusions:

From our study, we conclude that differential survival and therapy benefit of patients with breast cancer are characterized by distinct microenvironments that include specific populations of immune and epithelial cells.
Therapy-Related Transcriptional Subtypes in Matched Primary and Recurrent Head and Neck Cancer
Authors: Weber Peter , Künstner Axel , Hess Julia , Unger Kristian , Marschner Sebastian , Idel Christian , Ribbat-Idel Julika , Baumeister Philipp , Gires Olivier , Walz Christoph , Rietzler Sibylle , Valeanu Laura , Herkommer Timm , Kreutzer Lisa , Klymenko Olena , Drexler Guido , Kirchner Thomas , Maihöfer Cornelius , Ganswindt Ute , Walch Axel , Sterr Michael , Lickert Heiko , Canis Martin , Rades Dirk , Perner Sven , Berriel Diaz Mauricio , Herzig Stefan , Lauber Kirsten , Wollenberg Barbara , Busch Hauke , Belka Claus , Zitzelsberger Horst
Published: December 2021

Purpose:

The genetic relatedness between primary and recurrent head and neck squamous cell carcinomas (HNSCC) reflects the extent of heterogeneity and therapy-driven selection of tumor subpopulations. Yet, current treatment of recurrent HNSCC ignores the molecular characteristics of therapy-resistant tumor populations.

Experimental Design:

From 150 tumors, 74 primary HNSCCs were RNA sequenced and 38 matched primary/recurrent tumor pairs were both whole-exome and RNA sequenced. Transcriptome analysis determined the predominant classical (CL), basal (BA), and inflamed-mesenchymal (IMS) transcriptional subtypes according to an established classification. Genomic alterations and clonal compositions of tumors were evaluated from whole-exome data.

Results:

Although CL and IMS subtypes were more common in primary HNSCC with low recurrence rates, the BA subtype was more prevalent and stable in recurrent tumors. The BA subtype was associated with a transcriptional signature of partial epithelial-to-mesenchymal transition (p-EMT) and early recurrence. In 44% of matched cases, the dominant subtype changed from primary to recurrent tumors, preferably from IMS to BA or CL. Expression analysis of prognostic gene sets identified upregulation of hypoxia, p-emt, and radiotherapy resistance signatures and downregulation of tumor inflammation in recurrences compared with index tumors. A relevant subset of primary/recurrent tumor pairs presented no evidence for a common clonal origin.

Conclusions:

Our study showed a high degree of genetic and transcriptional heterogeneity between primary/recurrent tumors, suggesting therapy-related selection of a transcriptional subtype with characteristics unfavorable for therapy. We conclude that therapy decisions should be based on genetic and transcriptional characteristics of recurrences rather than primary tumors to enable optimally tailored treatment strategies.
Trabectedin plus Durvalumab in Patients with Advanced Pretreated Soft Tissue Sarcoma and Ovarian Carcinoma (TRAMUNE): An Open-Label, Multicenter Phase Ib Study
Authors: Toulmonde Maud , Brahmi Mehdi , Giraud Antoine , Chakiba Camille , Bessede Alban , Kind Michèle , Toulza Emilie , Pulido Marina , Albert Sabrina , Guégan Jean-Philippe , Cousin Sophie , Mathoulin-Pelissier Simone , Perret Raul , Croce Sabrina , Blay Jean-Yves , Ray-Coquard Isabelle , Floquet Anne , Italiano Antoine
Published: December 2021

Purpose:

Trabectedin has shown preclinical synergy with immune checkpoint inhibitors in preclinical models.

Patients and Methods:

TRAMUNE is a phase Ib study investigating the combination of trabectedin with durvalumab through a dose escalation phase and two expansion cohorts, soft tissue sarcoma (STS) and ovarian carcinoma. Trabectedin was given at three dose levels (1 mg/m2, 1.2 mg/m2, and 1.5 mg/m2) on day 1, in combination with durvalumab, 1,120 mg on day 2, every 3 weeks. The primary endpoints were the recommended phase II dose (RP2D) of trabectedin combined with durvalumab and the objective response rate (ORR) as per RECIST 1.1. The secondary endpoints included safety, 6-month progression-free rate (PFR), progression-free survival (PFS), overall survival, and biomarker analyses.

Results:

A total of 40 patients were included (dose escalation, n = 9; STS cohort, n = 16; ovarian carcinoma cohort, n = 15, 80% platinum resistant/refractory). The most frequent toxicities were grade 1–2 fatigue, nausea, neutropenia, and alanine/aspartate aminotransferase increase. One patient experienced a dose-limiting toxicity at dose level 2. Trabectedin at 1.2 mg/m2 was selected as the RP2D. In the STS cohort, 43% of patients experienced tumor shrinkage, the ORR was 7% [95% confidence interval (CI), 0.2–33.9], and the 6-month PFR was 28.6% (95% CI, 8.4–58.1). In the ovarian carcinoma cohort, 43% of patients experienced tumor shrinkage, the ORR was 21.4% (95% CI, 4.7–50.8), and the 6-month PFR was 42.9% (95% CI, 17.7–71.1). Baseline levels of programmed death-ligand 1 expression and CD8-positive T-cell infiltrates were associated with PFS in patients with ovarian carcinoma.

Conclusions:

Combining trabectedin and durvalumab is manageable. Promising activity is observed in patients with platinum-refractory ovarian carcinoma.

See related commentary by Digklia et al., p. 1745
Transcriptomic Determinants of Response to Pembrolizumab Monotherapy across Solid Tumor Types
Authors: Cristescu Razvan , Nebozhyn Michael , Zhang Chunsheng , Albright Andrew , Kobie Julie , Huang Lingkang , Zhao Qing , Wang Anran , Ma Hua , Alexander Cao Z. , Morrissey Michael , Ribas Antoni , Grivas Petros , Cescon David W. , McClanahan Terrill K. , Snyder Alexandra , Ayers Mark , Lunceford Jared , Loboda Andrey
Published: December 2021

Purpose:

To explore relationships between biological gene expression signatures and pembrolizumab response.

Experimental Design:

RNA-sequencing data on baseline tumor tissue from 1,188 patients across seven tumor types treated with pembrolizumab monotherapy in nine clinical trials were used. A total of 11 prespecified gene expression signatures [18-gene T-cell–inflamed gene expression profile (TcellinfGEP), angiogenesis, hypoxia, glycolysis, proliferation, MYC, RAS, granulocytic myeloid-derived suppressor cell (gMDSC), monocytic myeloid-derived suppressor cell (mMDSC), stroma/epithelial-to-mesenchymal transition (EMT)/TGFβ, and WNT] were evaluated for their relationship to objective response rate (per RECIST, version 1.1). Logistic regression analysis of response for consensus signatures was adjusted for tumor type, Eastern Cooperative Oncology Group performance status, and TcellinfGEP, an approach equivalent to evaluating the association between response and the residuals of consensus signatures after detrending them for their relationship with the TcellinfGEP (previously identified as a determinant of pembrolizumab response) and tumor type. Testing of the 10 prespecified non-TcellinfGEP consensus signatures for negative association [except proliferation (hypothesized positive association)] with response was adjusted for multiplicity.

Results:

Covariance patterns of the 11 signatures (including TcellinfGEP) identified in Merck–Moffitt and The Cancer Genome Atlas datasets showed highly concordant coexpression patterns in the RNA-sequencing data from pembrolizumab trials. TcellinfGEP was positively associated with response; signatures for angiogenesis, mMDSC, and stroma/EMT/TGFβ were negatively associated with response to pembrolizumab monotherapy.

Conclusions:

These findings suggest that features beyond IFNγ-related T-cell inflammation may be relevant to anti–programmed death 1 monotherapy response and may define other axes of tumor biology as candidates for pembrolizumab combinations.

See related commentary by Cho et al., p. 1479
Reverse Translating Molecular Determinants of Anti–Programmed Death 1 Immunotherapy Response in Mouse Syngeneic Tumor Models
Authors: Georgiev Peter , Muise Eric S. , Linn Douglas E. , Hinton Marlene C. , Wang Yun , Cai Mingmei , Cadzow Louise , Wilson Douglas C. , Sukumar Selvakumar , Caniga Michael , Chen Lan , Xiao Hui , Yearley Jennifer H. , Sriram Venkataraman , Nebozhyn Michael , Sathe Manjiri , Blumenschein Wendy M. , Kerr Kimberly S. , Hirsch Heather A. , Javaid Sarah , Olow Aleksandra K. , Moy Lily Y. , Chiang Derek Y. , Loboda Andrey , Cristescu Razvan , Sadekova Svetlana , Long Brian J. , McClanahan Terrill K. , Pinheiro Elaine M.
Published: December 2021

Targeting the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway with immunotherapy has revolutionized the treatment of many cancers. Somatic tumor mutational burden (TMB) and T-cell–inflamed gene expression profile (GEP) are clinically validated pan-tumor genomic biomarkers that can predict responsiveness to anti-PD-1/PD-L1 monotherapy in many tumor types. We analyzed the association between these biomarkers and the efficacy of PD-1 inhibitor in 11 commonly used preclinical syngeneic tumor mouse models using murinized rat anti-mouse PD-1 DX400 antibody muDX400, a surrogate for pembrolizumab. Response to muDX400 treatment was broadly classified into three categories: highly responsive, partially responsive, and intrinsically resistant to therapy. Molecular and cellular profiling validated differences in immune cell infiltration and activation in the tumor microenvironment of muDX400-responsive tumors. Baseline and on-treatment genomic analysis showed an association between TMB, murine T-cell–inflamed gene expression profile (murine-GEP), and response to muDX400 treatment. We extended our analysis to investigate a canonical set of cancer and immune biology-related gene signatures, including signatures of angiogenesis, myeloid-derived suppressor cells, and stromal/epithelial-to-mesenchymal transition/TGFβ biology previously shown to be inversely associated with the clinical efficacy of immune checkpoint blockade. Finally, we evaluated the association between murine-GEP and preclinical efficacy with standard-of-care chemotherapy or antiangiogenic agents that previously demonstrated promising clinical activity, in combination with muDX400. Our profiling studies begin to elucidate the underlying biological mechanisms of response and resistance to PD-1/PD-L1 blockade represented by these models, thereby providing insight into which models are most appropriate for the evaluation of orthogonal combination strategies.
Weight is More Informative than Body Mass Index for Predicting Postmenopausal Breast Cancer Risk: Prospective Family Study Cohort (ProF-SC)
Authors: Ye Zhoufeng , Li Shuai , Dite Gillian S. , Nguyen Tuong L. , MacInnis Robert J. , Andrulis Irene L. , Buys Saundra S. , Daly Mary B. , John Esther M. , Kurian Allison W. , Genkinger Jeanine M. , Chung Wendy K. , Phillips Kelly-Anne , Thorne Heather , Thorne Heather ,   for kConFab, Winship Ingrid M. , Milne Roger L. , Dugué Pierre-Antoine , Southey Melissa C. , Giles Graham G. , Terry Mary Beth , Hopper John L.
Published: December 2021

We considered whether weight is more informative than body mass index (BMI) = weight/height2 when predicting breast cancer risk for postmenopausal women, and if the weight association differs by underlying familial risk. We studied 6,761 women postmenopausal at baseline with a wide range of familial risk from 2,364 families in the Prospective Family Study Cohort. Participants were followed for on average 11.45 years and there were 416 incident breast cancers. We used Cox regression to estimate risk associations with log-transformed weight and BMI after adjusting for underlying familial risk. We compared model fits using the Akaike information criterion (AIC) and nested models using the likelihood ratio test. The AIC for the weight-only model was 6.22 units lower than for the BMI-only model, and the log risk gradient was 23% greater. Adding BMI or height to weight did not improve fit (ΔAIC = 0.90 and 0.83, respectively; both P = 0.3). Conversely, adding weight to BMI or height gave better fits (ΔAIC = 5.32 and 11.64; P = 0.007 and 0.0002, respectively). Adding height improved only the BMI model (ΔAIC = 5.47; P = 0.006). There was no evidence that the BMI or weight associations differed by underlying familial risk (P > 0.2). Weight is more informative than BMI for predicting breast cancer risk, consistent with nonadipose as well as adipose tissue being etiologically relevant. The independent but multiplicative associations of weight and familial risk suggest that, in terms of absolute breast cancer risk, the association with weight is more important the greater a woman's underlying familial risk.

Prevention Relevance:

Our results suggest that the relationship between BMI and breast cancer could be due to a relationship between weight and breast cancer, downgraded by inappropriately adjusting for height; potential importance of anthropometric measures other than total body fat; breast cancer risk associations with BMI and weight are across a continuum.
Treating Agitation in Patients with Dementia with a Therapy Dog in a Milieu Therapy Setting on a Geropsychiatric Ward
Authors: Krüger Jana , Izgi Reyhan , Hellweg Rainer , Ströhle Andreas , Jockers-Scherübl Maria C.
Published: December 2021

Background: Animal-assisted intervention has become a common therapeutic practice used for patients with dementia in home-dwelling and institutions. The most established procedure is a visiting service by specially trained dogs and their owners to improve social interactions and reduce symptoms of agitation. Objectives: The study aims to investigate the effects of a therapy dog on agitation of inpatients with dementia in a gerontopsychiatric ward. Materials and Methods: The severity of agitation was assessed by a rater blinded for the presence of the dog via the Overt Agitation Severity Scale (OASS). The scale was conducted on 1 day with the dog and his handler present (resident doctor on the ward) and on another day with only the handler present. Each patient was his/her own control. Heart rate variability (HRV) and serum level of brain-derived neurotrophic factor (BDNF) of the patients were measured on both days. 26 patients with the Mini-Mental Status Examination (MMSE) score <21 and the diagnosis of dementia were included in the study. Results: A significant reduction of agitation in the OASS could be shown when the dog was present (p = 0.006). The data neither demonstrated a difference in the HRV for the parameters mean heart rate (p = 0.65), root mean square of successive differences (p = 0.63), and high frequencies (p = 0.27) nor in serum BDNF concentrations (p = 0.42). Discussion: Therapy dogs can be implemented as a therapeutic tool in a gerontopsychiatric ward to reduce symptoms of agitation in patients with dementia. The study was registered in the German Clinical Trials Register (DRKS00024093).
Development of Urinary Diagnostic Biomarker for IgA Nephropathy by Lectin Microarray
Authors: Onishi Yasuhiro , Mise Koki , Kawakita Chieko , Uchida Haruhito A. , Sugiyama Hitoshi , Sugawara Ryosuke , Yamaguchi Satoshi , Yoshida Michihiro , Mitsuhashi Toshiharu , Yamada Masao , Hirabayashi Jun , Wada Jun
Published: December 2021

Introduction: The pathogenic roles of aberrantly glycosylated IgA1 have been reported. However, it is unexplored whether the profiling of urinary glycans contributes to the diagnosis of IgAN. Methods: We conducted a retrospective study enrolling 493 patients who underwent renal biopsy at Okayama University Hospital between December 2010 and September 2017. We performed lectin microarray in urine samples and investigated whether c-statistics of the reference standard diagnosis model employing hematuria, proteinuria, and serum IgA were improved by adding the urinary glycan intensity. Results: Among 45 lectins, 3 lectins showed a significant improvement of the models: Amaranthus caudatus lectin (ACA) with the difference of c-statistics 0.038 (95% CI: 0.019–0.058, p < 0.001), Agaricus bisporus lectin (ABA) 0.035 (95% CI: 0.015–0.055, p < 0.001), and Maackia amurensis lectin (MAH) 0.035 (95% CI: 0.015–0.054, p < 0.001). In 3 lectins, each signal plus reference standard showed good reclassification (category-free NRI and relative IDI) and good model fitting associated with the improvement of AIC and BIC. Stratified by eGFR, the discriminatory ability of ACA plus reference standard was maintained, suggesting the robust renal function-independent diagnostic performance of ACA. By decision curve analysis, there was a 3.45% net benefit by adding urinary glycan intensity of ACA to the reference standard at the predefined threshold probability of 40%. Conclusions: The reduction of Gal(β1-3)GalNAc (T-antigen), Sia(α2-3)Gal(β1-3)GalNAc (Sialyl T), and Sia(α2-3)Gal(β1-3)Sia(α2-6)GalNAc (disialyl-T) was suggested by binding specificities of 3 lectins. C1GALT1 and COSMC were responsible for the biosynthesis of these glycans, and they were known to be downregulated in IgAN. The urinary glycan analysis by ACA is a useful and robust noninvasive strategy for the diagnosis of IgAN.
Criminal Law & Migration Control: Recent History & Future
Possibilities
Authors: Chacón Jennifer M.
Published: December 2021

Immigration enforcement in the United States has undergone a revolutionary transformation over the past three decades. Once episodic, border-focused, and generally confined to the efforts of a relatively small federal agency, immigration enforcement is now exceedingly well-funded and integrated deeply into the everyday policing of the interior United States. Not only are federal immigration agents more numerous and ubiquitous in the interior, but immigration enforcement has been integrated into the policing practices of state and local officials who once saw their purview as largely distinct from that of federal immigration enforcement agents. This essay briefly explains these developments, from shortly before the passage of the Immigration Reform and Control Act of 1986 through the present day, and assesses their consequences. It includes a brief discussion of the ways states and localities have responded to federal enforcement trends, whether through amplification or constraint.
The Cortical Organization of Syntactic Processing Is Supramodal: Evidence from American Sign Language
Authors: Matchin William , İlkbaşaran Deniz , Hatrak Marla , Roth Austin , Villwock Agnes , Halgren Eric , Mayberry Rachel I.
Published: December 2021

Areas within the left-lateralized neural network for language have been found to be sensitive to syntactic complexity in spoken and written language. Previous research has revealed that these areas are active for sign language as well, but whether these areas are specifically responsive to syntactic complexity in sign language independent of lexical processing has yet to be found. To investigate the question, we used fMRI to neuroimage deaf native signers' comprehension of 180 sign strings in American Sign Language (ASL) with a picture-probe recognition task. The ASL strings were all six signs in length but varied at three levels of syntactic complexity: sign lists, two-word sentences, and complex sentences. Syntactic complexity significantly affected comprehension and memory, both behaviorally and neurally, by facilitating accuracy and response time on the picture-probe recognition task and eliciting a left lateralized activation response pattern in anterior and posterior superior temporal sulcus (aSTS and pSTS). Minimal or absent syntactic structure reduced picture-probe recognition and elicited activation in bilateral pSTS and occipital-temporal cortex. These results provide evidence from a sign language, ASL, that the combinatorial processing of anterior STS and pSTS is supramodal in nature. The results further suggest that the neurolinguistic processing of ASL is characterized by overlapping and separable neural systems for syntactic and lexical processing.
Active Working Memory and Simple Cognitive Operations
Authors: Kreither Johanna , Papaioannou Orestis , Luck Steven J.
Published: December 2021

Working memory is thought to serve as a buffer for ongoing cognitive operations, even in tasks that have no obvious memory requirements. This conceptualization has been supported by dual-task experiments, in which interference is observed between a primary task involving short-term memory storage and a secondary task that presumably requires the same buffer as the primary task. Little or no interference is typically observed when the secondary task is very simple. Here, we test the hypothesis that even very simple tasks require the working memory buffer, but interference can be minimized by using activity-silent representations to store the information from the primary task. We tested this hypothesis using dual-task paradigm in which a simple discrimination task was interposed in the retention interval of a change detection task. We used contralateral delay activity (CDA) to track the active maintenance of information for the change detection task. We found that the CDA was massively disrupted after the interposed task. Despite this disruption of active maintenance, we found that performance in the change detection task was only slightly impaired, suggesting that activity-silent representations were used to retain the information for the change detection task. A second experiment replicated this result and also showed that automated discriminations could be performed without producing a large CDA disruption. Together, these results suggest that simple but non-automated discrimination tasks require the same processes that underlie active maintenance of information in working memory.
Art Work as Life Work: Lu Märten's Feminist “Objectivity”
Authors: Nachtigall Jenny , Stakemeier Kerstin
Published: December 2021

“Art Work as Life Work: Lu Märten's Feminist ‘Objectivity’” highlights the feminist stakes of German feminist-materialist art historian Lu Märten's interventions in the interwar discourses on art and labor, on objectivity (Sachlichkeit), and the new media of film and radio. The essay argues that Märten's contributions to these areas sit squarely within more familiar narratives of materialist aesthetics and Weimar culture (from Walter Benjamin's epochal Artwork Essay to the Bauhaus) and that they do so on account of her heterodox reading of Marx and commitment to Spinoza's monism. In Märten's view, this non-binary materialism offered an alternative, non-Hegelian route to a materialist conception of art or as she preferred to say, form. In contrast to art history's academic formalism, Märten espouses a notion of form that does not maintain art's autonomy but instead connects art to other social fields. Here form always evolves out of informality. The essay traces the close bond between art work and life work across Märten's multiple publications, including her theoretical magnum opus Essence and Transformation of Forms/Arts and her studies on The Economic Conditions of Artists and The Female Artist. In so doing, the text contributes to revisiting the firm boundaries that art history has drawn between objects and communities.
Lubitsch, Shakespeare, and the Theatricality of Power
Authors: Moder Gregor
Published: December 2021

Ernst Lubitsch's To Be or Not to Be (1942) was filmed during World War II and takes place in the early period of the Nazi occupation of Poland, yet it focuses on the story of a theater group, on actors, and on the metaphysical question of what makes up a convincing performance. Some early critics suggested that this was not the way to tackle a dire political situation, and that the portrayal of Nazis as humans, with their own sense of humor and theater, was disrespectful to the plight of the Poles and Polish Jewry. For the film, however, the political action and the tracing of the philosophical implications of a theatrical performance are not alternative procedures, but are closely linked to one another, and in this respect Lubitsch follows Shakespeare's own staging of power. The article pursues this argument, firstly, in the analysis of the series of Shylock monologues in the film (“Hath not a Jew eyes?”), focusing on the hyper-theatricality of each repetition. Secondly, it analyzes the series of encounters between two main characters, the Nazi Colonel Ehrhardt and the Polish actor Joseph Tura, especially their last encounter. The author compares the encounter between Ehrhardt and Tura to the Mousetrap scene in Hamlet and argues that it functions as the primal scene—in the Freudian meaning of the term—of the film as such. Their encounter is comical, yet at the same time both politically and metaphysically completely serious: The film shows us two visions of Hamlet, and with that, two visions of modernity, embodied in a Nazi colonel and a Polish actor. The film seems to suggest that there is no defeating Nazism without a thorough understanding of the theatricality of power as such—a Shakespearean lesson that is vital also for our contemporary moment.
Les désarrois du ministre Ḫayr al-Dīn : la faillite des dynasties ottomane et beylicale d’après les mémoires de Ṭāhar Bāšā (1921-1934)
Authors: Perrier Antoine
Published: December 2021

Ṭāhar Bāšā Ḫayr al-Dīn, né à Istanbul, officier ottoman, occupe le poste de ministre de la justice de la province de Tunis alors sous protectorat français de 1921 à 1934. Il a laissé un témoignage historique précieux : des mémoires, compilés sous forme de notes par des universitaires tunisiens et publiés dans leur langue originale, en arabe, en 1989. Cet article propose une traduction de quelques extraits et l’analyse d’une source historique de premier ordre, ignorée de l’historiographie française, utile à l’histoire des dynasties ottomane et tunisienne.

À travers la trajectoire singulière du fils de Ḫayr al-Dīn Bāšā, qui prend le chemin inverse de son père d’Istanbul à Tunis, et l’analyse des portraits de trois beys de Tunisie, nous voudrions souligner l’importance de cette source à trois égards. Par les portraits de la cour, ce document jette une nouvelle lumière sur une dynastie victime d’une damnatio memoriae en Tunisie après l’indépendance, en soulignant ses résistances et sa capacité d’adaptation à la période coloniale. Les mémoires de Ṭāhar Bāšā invitent ensuite à réfléchir à l’originalité et au statut d’une source « locale » en contexte colonial, depuis le regard d’un allié (critique) des Français. Enfin, cette source permet de réfléchir à l’émergence du genre des mémoires d’homme d’État et l’originalité d’un regard fondé sur un profond pessimisme.
A Papyrus Fragment Related to Ibn ʿAbd Rabbih’s al-ʿIqd al-farīd*
Authors: Muehlhaeusler Mark
Published: December 2021

This article presents an edition and a translation of a papyrus fragment from the Beinecke Library at Yale (P.CtYBR inv. 2598), together with a brief commentary. This literary fragment, containing two verses of poetry, is interesting because it provides an oriental source for a text until then known only through the famous Andalusian work of Ibn ʿAbd Rabbih, al-ʿIqd al-farīd; it also serves as an example of an informal mode of written transmission of Arabic poetry.
Exploiting the Urban System? The Frictions of Military Finance and Diplomacy in the Dutch Republic, 1688–1714
Authors: Graham Aaron , Kamp Jeannette
Published: December 2021

This article examines how international military finance operated in the Dutch Republic between 1688–1714. The region’s unique urban geography in which the political and financial infrastructures crucial for military financing were geographically dispersed created stresses and strains. These inconveniences were overcome due to the Republic’s excellent intra-urban infrastructure – creating fast and reliable communication between the different urban centers – and their reliance on (semi-)private agents, the solliciteurs-militair. As a result, the urban system created a level of flexibility: credit for military purposes could be found both in The Hague and Amsterdam, rather than having to rely on a single city as was the case in London. This focus on the urban has broader historiographical importance because recent scholarship on early modern war and state formation is increasingly questioning whether the focus on political and financial centralization is necessarily the best way to understand these processes.
Procedural Developments at the International Criminal Court (2020)
Authors: Le Floch Guillaume , Lemey Marie , Paiola Lucie
Published: December 2021

The current column covers selected procedural developments at the International Criminal Court (ICC) in 2020. During this particular year, the Court has undertaken a multi-layered response to mitigate the effects of the COVID-19 pandemic on its operations. The ICC temporarily closed its headquarters building in The Hague from March to June 2020. Nevertheless, the Court successfully implemented, in a short timeframe, new remote working arrangements to ensure business continuity. These measures have allowed it to maintain a certain productivity. As a result, during the reporting period, the ICC delivered numerous decisions, taking such opportunities to clarify specific aspects of proceedings before the Court.
Overview of Education in Ethiopia: Traditional Institutions and Language Perspectives
Authors: Chali Gemechis T. , Taverniers Miriam , Legesse Guta
Published: December 2021

This article briefly introduces the phases of education in Ethiopia in the last 150 years and the impact of traditional institutions on languages. The intention of this report is to present the background section of a PhD (Gemechis, 2020) defended at Ghent University in September 2020. It is believed that the period of modern education in Ethiopia is shorter when compared with that of traditional education, which lasted for more than a century. Modern or “Western” education was launched in 1908, and Western educational ideas have flourished since the early twentieth century; but the traditional approach characterised Ethiopian education throughout the history of this ancient nation (Hoot, Szente and Mebratu, 2004). This article aims to review the past 150 years of education in Ethiopia in connection with historical trends and the influence of traditional institutions on education in general and languages in particular. Respondents discuss the fact that that, unlike the Orthodox and Missionary churches in Ethiopia, some of the traditional institutions such as the Waaqqeffannaa of Oromoo Institution were not allowed to reflect their values and languages. The study reveals that traditional institutions have played a crucial role in education in Ethiopia. Furthermore, understanding the impact of languages in education is important in teaching and learning in general. However, the findings confirm that there was no structure that could equally understand and accommodate all traditional institutions to contribute to the education of Ethiopia in the past. This article concludes with the recommendation that there should be a well-established implementation system on the languages and cultural institutions that could attract all nations and nationalities to promote their traditional institutions. For instance, there are no language and cultural policies aimed at sustainability.
The Impact of River Regulation on Downstream Socio-Hydrologic Systems in Ethiopia
Authors: Annys Sofie
Published: December 2021

In recent years, a renewed interest in large-scale hydraulic interventions has developed, frequently justified by the premise of making the agricultural and energy sectors climate-resilient. Despite this important climate effort, hydraulic interventions are controversial and have far-reaching impacts on river-dependent communities and the environment. Drawing on gis analyses of remote sensing images and qualitative and quantitative empirical evidence from the field, this PhD dissertation focused on the impact of two large dams and one inter-basin water transfer (ibwt) on downstream socio-hydrologic systems (coupled human-water systems) in Ethiopia. The results indicated that (i) downstream hydrogeomorphic systems drastically altered after the implementation of the hydraulic interventions, (ii) small-scale farmer-led irrigation systems more efficiently increased crop productivities than several large-scale irrigation projects, (iii) the newly induced hydrologic regimes strongly altered downstream social interactions due to impeded river crossing and (iv) ill-prepared land redistributions and resettlements left thousands of households with a high risk of impoverishment.
First Evidence of Stage III Verbal Negation in Tunisian Coastal Dialects
Authors: D’Anna Luca
Published: December 2021

The present paper provides a preliminary description of verbal negation in the two neighboring dialects of Mahdia and Chebba, belonging to the groups of Tunisian coastal village dialects. This dialectal group has been, so far, dramatically understudied, despite its importance for the dialectal geography and history of North African Arabic. Like most other varieties of Maghrebi Arabic, the dialects of Mahdia and Chebba underwent the so-called Jespersen’s cycle, consisting in the doubling of the original prefixal negation, in dialectal Arabic mā (Stage I), with a suffixal negative particle -š, resulting in the circumfixal negation mā … š (Stage II) and, eventually, in the loss of the prefixal mā (Stage III). With regard to Arabic, Stage III was so far undocumented in North Africa, with the exception of Maltese. This paper provides samples of the three different stages in the dialects under investigation and offers some hypotheses concerning the possible locus of innovation with regard to Tunisian, contributing to our knowledge of negation in North African Arabic.