bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using geospatial models to map zero-dose children: factors associated with zero-dose vaccination status before and after a mass measles and rubella vaccination campaign in Southern province, Zambia
Authors: Arambepola Rohan , Yang Yangyupei , Hutchinson Kyle , Mwansa Francis Dien , Doherty Julie Ann , Bwalya Frazer , Ndubani Phillimon , Musukwa Gloria , Moss William John , Wesolowski Amy , Mutembo Simon 
Published: December 2021

IntroductionDespite gains in global coverage of childhood vaccines, many children remain undervaccinated. Although mass vaccination campaigns are commonly conducted to reach these children their effectiveness is unclear. We evaluated the effectiveness of a mass vaccination campaign in reaching zero-dose children.MethodsWe conducted a prospective study in 10 health centre catchment areas in Southern province, Zambia in November 2020. About 2 months before a national mass measles and rubella vaccination campaign conducted by the Ministry of Health, we used aerial satellite maps to identify built structures. These structures were visited and diphtheria-tetanus-pertussis (DTP) and measles zero-dose children were identified (children who had not received any DTP or measles-containing vaccines, respectively). After the campaign, households where measles zero-dose children were previously identified were targeted for mop-up vaccination and to assess if these children were vaccinated during the campaign. A Bayesian geospatial model was used to identify factors associated with zero-dose status and measles zero-dose children being reached during the campaign. We also produced fine-scale zero-dose prevalence maps and identified optimal locations for additional vaccination sites.ResultsBefore the vaccination campaign, 17.3% of children under 9 months were DTP zero-dose and 4.3% of children 9–60 months were measles zero-dose. Of the 461 measles zero-dose children identified before the vaccination campaign, 338 (73.3%) were vaccinated during the campaign and 118 (25.6%) were reached by a targeted mop-up activity. The presence of other children in the household, younger age, greater travel time to health facilities and living between health facility catchment areas were associated with zero-dose status. Mapping zero-dose prevalence revealed substantial heterogeneity within and between catchment areas. Several potential locations were identified for additional vaccination sites.ConclusionFine-scale variation in zero-dose prevalence and the impact of accessibility to healthcare facilities on vaccination coverage were identified. Geospatial modelling can aid targeted vaccination activities.
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.
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract
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

AbstractWe 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 &gt; 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.
Criminal Law & Migration Control: Recent History & Future
Possibilities
Authors: Chacón Jennifer M. 
Published: December 2021

Abstract
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

Abstract
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.