bluuebunny/crossref_metadata_2025_split huggingface dataset:
The carbon footprint of clinical trials: a global survey on the status quo and current regulatory guidance
Authors: Hoffmann Jean-Marc , Bauer Annina , Grossmann Regina 
Published: September 2023

IntroductionAll economic sectors including the service sector, along with healthcare, education and research, need to reduce their greenhouse gas emissions to limit global temperature increases. In this study, we aim to globally assess the awareness and current actions taken by Academic Research Institutions (ARIs) or governments regarding the reduction of carbon dioxide equivalent (CO2e) emissions for clinical research.MethodsWe designed a cross-sectional survey-based study, which was distributed within the International Clinical Trials Center Network (ICN). The survey population comprised representatives of the ICN who had extensive experience in academic clinical research and profound knowledge and understanding of the local context.ResultsThe response rate was 80%. Responding ARIs were from 15 different countries and 4 continents. Around half of the ARIs reported that almost none of their research projects considered reducing their carbon footprint. The other half of the ARIs were not familiar with this subject at all. According to 60% of the respondents, greenhouse gas emissions are not assessed by Institutional Review Boards (IRBs)/Ethics Committees (ECs) or competent authorities, while 40% did not know. Neither IRBs/ECs nor competent authorities currently advise sponsors and investigators on reducing the carbon footprint of their clinical research projects. As for reducing greenhouse gas emissions in clinical research, virtual conferences and meetings were the most commonly implemented measures by ARIs across all regions. Finally, we have put together an action plan/checklist advising researchers on carbon footprint reduction for clinical trials.ConclusionCurrently, greenhouse gas emissions are neglected during the planning phase of a research project, and they are not yet addressed or assessed by default during the approval procedures by IRBs/ECs or competent authorities. Thus, all involved stakeholders within clinical research need to be made aware of it through advice from ARIs and IRBs/ECs, among others.
Socio-economic factors associated with open defecation among agricultural households: a cross-sectional study in Haiti
Authors: Paul Bénédique 
Published: September 2023

BackgroundOpen defecation (OD) is recognised as an important public health challenge in low-income and middle-income countries. Although agriculture is the main occupation in these countries, few if any study on OD has focused on agricultural households. In order to enhance the prevention of OD and contribute to a better understanding of this health-threatening behaviour, this paper analyses the socio-economic factors associated with OD practice among agricultural households in Haiti.MethodsThe study used primary data from 1269 households selected in 5 out of 10 geographic departments of Haiti surveyed in 2020–2021. Descriptive statistics and bivariate analysis were used to identify households’ characteristics that were significantly associated with OD. In addition, a multivariate analysis was performed using binary logistic regression to study the factors associated with the probability to defecate in the open.ResultsFindings show that one out of five (20.1%) agricultural households in Haiti practices OD. More than 26% of the households did not have any member with secondary school education level. Multivariate analysis revealed that in addition to the location, the probability of OD practices among agricultural households was correlated with socio-economic factors such as education, access to the media, plot number and livestock, level of specialisation in the agriculture, agricultural income and participation in local organisations.ConclusionWhile Haiti is struggling with cholera among other health issues, this paper sheds light on factors associated with OD, a health-threatening and unsustainable sanitation behaviour. According to the results, in addition to toilet acquisition subsidies, awareness campaigns need to make use of mass media and local organisations particularly women and community ones. Elimination of OD among agricultural households is of great significance for better quality of foods and vegetables at watershed level.
The 2020 US cancer screening deficit and the timing of adults’ most recent screen: a population-based cross-sectional study
Authors: Semprini Jason , Ranganathan Radhika 
Published: September 2023

ObjectiveIn 2020, cancer screenings declined, resulting in a cancer screening deficit. The significance of this deficit, however, has yet to be quantified from a population health perspective. Our study addresses this evidence gap by examining how the pandemic changed the timing of American adults’ most recent cancer screen.MethodologyWe obtained population-based, cancer screening data from the Behavioural Risk Factor Surveillance System (BRFSS) (2010, 2012, 2014, 2016, 2018, 2020). Mammograms, pap smears and colonoscopies were each specified as a variable of mutually exclusive categories to indicate the timing since the most recent screening (never, 0–1 years, 1–2 years, 3+ years). Our cross-sectional, quasi-experimental design restricts the sample to adults surveyed in January, February or March. We then leverage a quirk in the BRFSS implementation and consider adults surveyed in the second year of the 2020 survey wave as exposed to the COVID-19 pandemic. Respondents surveyed in January 2020–March 2020 were considered unexposed. To estimate the impact of exposure to the COVID-19 pandemic on the timing of recent cancer screenings, we constructed linear and logistic regression models which control for sociodemographic characteristics associated with screening patterns, and state fixed effects and temporal trend fixed effects to control for confounding.ResultsIn 2020, the cancer screening deficit was largely due to a 1 year delay among adults who receive annual screening, as the proportion of adults reporting a cancer screen in the past year declined by a nearly identical proportion of adults reporting their most recent cancer screen 1–2 years ago (3%–4% points). However, the relative change was higher for mammograms and pap smears (17%) than colonoscopies (4%). We also found some evidence that the proportion of women reporting never having completed a mammogram declined in 2020, but the mechanisms for this finding should be further explored with the release of future data.ConclusionOur estimates for the pandemic’s effect on cancer screening rates are smaller than prior studies. Because we account for temporal trends, we believe prior studies overestimated the effect of the pandemic and underestimated the overall downward trend in cancer screenings across the country leading up to 2020.
Advancing Direct Convolution Using Convolution Slicing Optimization and ISA Extensions
Authors: Ferrari Victor , Sousa Rafael , Pereira Marcio , L. De Carvalho João P. , Amaral José Nelson , Moreira José , Araujo Guido 
Published: September 2023

Convolution is one of the most computationally intensive operations that must be performed for machine learning model inference. A traditional approach to computing convolutions is known as the Im2Col + BLAS method. This article proposes SConv: a direct-convolution algorithm based on an MLIR/LLVM code-generation toolchain that can be integrated into machine-learning compilers. This algorithm introduces: (a) Convolution Slicing Analysis (CSA)—a convolution-specific 3D cache-blocking analysis pass that focuses on tile reuse over the cache hierarchy; (b) Convolution Slicing Optimization—a code-generation pass that uses CSA to generate a tiled direct-convolution macro-kernel; and (c) Vector-based Packing—an architecture-specific optimized input-tensor packing solution based on vector-register shift instructions for convolutions with unitary stride. Experiments conducted on 393 convolutions from full ONNX-MLIR machine learning models indicate that the elimination of the Im2Col transformation and the use of fast packing routines result in a total packing time reduction, on full model inference, of 2.3×–4.0× on Intel x86 and 3.3×–5.9× on IBM POWER10. The speed-up over an Im2Col + BLAS method based on current BLAS implementations for end-to-end machine-learning model inference is in the range of 11%–27% for Intel x86 and 11%–34% for IBM POWER10 architectures. The total convolution speedup for model inference is 13%–28% on Intel x86 and 23%–39% on IBM POWER10. SConv also outperforms BLAS GEMM, when computing pointwise convolutions in more than 82% of the 219 tested instances.
Fatty Acid Oxidation Mediated by Malonyl-CoA Decarboxylase Represses Renal Cell Carcinoma Progression
Authors: Zhou Lijie , Luo Yongbo , Liu Yuenan , Zeng Youmiao , Tong Junwei , Li Mengting , Hou Yaxin , Du Kaixuan , Qi Yabin , Pan Wenbang , Liu Yuanhao , Wang Rongli , Tian Fengyan , Gu Chaohui , Chen Ke 
Published: September 2023

Abstract

Fatty acid metabolism reprogramming is a prominent feature of clear cell renal cell carcinoma (ccRCC). Increased lipid storage supports ccRCC progression, highlighting the importance of understanding the molecular mechanisms driving altered fatty acid synthesis in tumors. Here, we identified that malonyl-CoA decarboxylase (MLYCD), a key regulator of fatty acid anabolism, was downregulated in ccRCC, and low expression correlated with poor prognosis in patients. Restoring MLYCD expression in ccRCC cells decreased the content of malonyl CoA, which blocked de novo fatty acid synthesis and promoted fatty acid translocation into mitochondria for oxidation. Inhibition of lipid droplet accumulation induced by MLYCD-mediated fatty acid oxidation disrupted endoplasmic reticulum and mitochondrial homeostasis, increased reactive oxygen species levels, and induced ferroptosis. Moreover, overexpressing MLYCD reduced tumor growth and reversed resistance to sunitinib in vitro and in vivo. Mechanistically, HIF2α inhibited MLYCD translation by upregulating expression of eIF4G3 microexons. Together, this study demonstrates that fatty acid catabolism mediated by MLYCD disrupts lipid homeostasis to repress ccRCC progression. Activating MLYCD-mediated fatty acid metabolism could be a promising therapeutic strategy for treating ccRCC.

Significance:
MLYCD deficiency facilitates fatty acid synthesis and lipid droplet accumulation to drive progression of renal cell carcinoma, indicating inducing MYLCD as a potential approach to reprogram fatty acid metabolism in kidney cancer.
Genome-Wide CRISPR Screens Identify Multiple Synthetic Lethal Targets That Enhance KRASG12C Inhibitor Efficacy
Authors: Mukhopadhyay Suman , Huang Hsin-Yi , Lin Ziyan , Ranieri Michela , Li Shuai , Sahu Soumyadip , Liu Yingzhuo , Ban Yi , Guidry Kayla , Hu Hai , Lopez Alfonso , Sherman Fiona , Tan Yi Jer , Lee Yeuan Ting , Armstrong Amanda P. , Dolgalev Igor , Sahu Priyanka , Zhang Tinghu , Lu Wenchao , Gray Nathanael S. , Christensen James G. , Tang Tracy T. , Velcheti Vamsidhar , Khodadadi-Jamayran Alireza , Wong Kwok-Kin , Neel Benjamin G. 
Published: September 2023

Abstract

Non–small lung cancers (NSCLC) frequently (∼30%) harbor KRAS driver mutations, half of which are KRASG12C. KRAS-mutant NSCLC with comutated STK11 and/or KEAP1 is particularly refractory to conventional, targeted, and immune therapy. Development of KRASG12C inhibitors (G12Ci) provided a major therapeutic advance, but resistance still limits their efficacy. To identify genes whose deletion augments efficacy of the G12Cis adagrasib (MRTX-849) or adagrasib plus TNO155 (SHP2i), we performed genome-wide CRISPR/Cas9 screens on KRAS/STK11-mutant NSCLC lines. Recurrent, potentially targetable, synthetic lethal (SL) genes were identified, including serine–threonine kinases, tRNA-modifying and proteoglycan synthesis enzymes, and YAP/TAZ/TEAD pathway components. Several SL genes were confirmed by siRNA/shRNA experiments, and the YAP/TAZ/TEAD pathway was extensively validated in vitro and in mice. Mechanistic studies showed that G12Ci treatment induced gene expression of RHO paralogs and activators, increased RHOA activation, and evoked ROCK-dependent nuclear translocation of YAP. Mice and patients with acquired G12Ci- or G12Ci/SHP2i-resistant tumors showed strong overlap with SL pathways, arguing for the relevance of the screen results. These findings provide a landscape of potential targets for future combination strategies, some of which can be tested rapidly in the clinic.

Significance:
Identification of synthetic lethal genes with KRASG12C using genome-wide CRISPR/Cas9 screening and credentialing of the ability of TEAD inhibition to enhance KRASG12C efficacy provides a roadmap for combination strategies.
See related commentary by Johnson and Haigis, p. 4005
Tumor-Infiltrating Normal B Cells Revealed by Immunoglobulin Repertoire Clonotype Analysis Are Highly Prognostic and Crucial for Antitumor Immune Responses in DLBCL
Authors: Xu-Monette Zijun Y. , Li Yong , Snyder Thomas , Yu Tiantian , Lu Tingxun , Tzankov Alexandar , Visco Carlo , Bhagat Govind , Qian Wenbin , Dybkaer Karen , Chiu April , Tam Wayne , Zu Youli , Hsi Eric D. , Hagemeister Fredrick B. , Wang Yingjun , Go Heounjeong , Ponzoni Maurilio , Ferreri Andrés J.M. , Møller Michael B. , Parsons Benjamin M. , Fan Xiangshan , van Krieken J. Han , Piris Miguel A. , Winter Jane N. , Au Qingyan , Kirsch Ilan , Zhang Mingzhi , Shaughnessy John , Xu Bing , Young Ken H. 
Published: September 2023

Abstract

Purpose:
Tumor-infiltrating B lymphocytes (TIL-B) have demonstrated prognostic and predictive significance in solid cancers. In this study, we aimed to distinguish TIL-Bs from malignant B-cells in diffuse large B-cell lymphoma (DLBCL) and determine the clinical and biological significance.

Experimental Design:
A total of 269 patients with de novo DLBCL from the International DLBCL R-CHOP Consortium Program were studied. Ultra-deep sequencing of the immunoglobulin genes was performed to determine B-cell clonotypes. The frequencies and numbers of TIL-B clonotypes in individual repertoires were correlated with patient survival, gene expression profiling (GEP) data, and frequencies of DLBCL-infiltrating immune cells quantified by fluorescent multiplex IHC at single-cell resolution.

Results:
TIL-B abundance, evaluated by frequencies of normal B-cell clonotypes in the immunoglobulin repertoires, remarkably showed positive associations with significantly better survival of patients in our sequenced cohorts. DLBCLs with high versus low TIL-B abundance displayed distinct GEP signatures, increased pre-memory B-cell state and naïve CD4 T-cell state fractions, and higher CD4+ T-cell infiltration. TIL-B frequency, as a new biomarker in DLBCL, outperformed the germinal center (GC) B-cell–like/activated B-cell–like classification and TIL-T frequency. The identified TIL-B–high GEP signature, including genes upregulated during T-dependent B-cell activation and those highly expressed in normal GC B cells and T cells, showed significant favorable prognostic effects in several external validation cohorts.

Conclusions:
TIL-B frequency is a significant prognostic factor in DLBCL and plays a crucial role in antitumor immune responses. This study provides novel insights into the prognostic determinants in DLBCL and TIL-B functions with important therapeutic implications.
Methylated DNA Markers for Sporadic Colorectal and Endometrial Cancer Are Strongly Associated with Lynch Syndrome Cancers
Authors: Bramblet Rachel M. , Bakkum-Gamez Jamie N. , Slettedahl Seth W. , Foote Patrick H. , Taylor William R. , Berger Calise K. , Gysbers Brianna J. , Arndt Jacquelyn , Chen Longwen , Doering Karen A. , Burger Kelli N. , Mahoney Douglas W. , Sherman Mark E. , Kisiel John B. , Samadder N. Jewel 
Published: September 2023

AbstractLynch syndrome (LS) markedly increases risks of colorectal and endometrial cancers. Early detection biomarkers for LS cancers could reduce the needs for invasive screening and surgical prophylaxis.To validate a panel of methylated DNA markers (MDM) previously identified in sporadic colorectal cancer and endometrial cancer for discrimination of these cancers in LS.In a case–control design, previously identified MDMs for the detection of colorectal cancer and endometrial cancer were assayed by qMSP on tissue-extracted DNA. Results were normalized to ACTB values within each sample. Least absolute shrinkage and selection operator models to classify colorectal cancer and endometrial cancer were trained on sporadic cases and controls and then applied to classify colorectal cancer and endometrial cancer, in those with LS, and cross-validated.We identified colorectal cancer cases (23 with LS, 48 sporadic), colorectal controls (32 LS, 48 sporadic), endometrial cancer cases (30 LS, 48 sporadic), and endometrial controls (29 LS, 37 sporadic). A 3-MDM panel (LASS4, LRRC4, and PPP2R5C) classified LS-CRC from LS controls with an AUC of 0.92 (0.84–0.99); results were similar for sporadic colorectal cancer. A 6-MDM panel (SFMBT2, MPZ, CYTH2, DIDO1, chr10.4479, and EMX2OS) discriminated LS-EC from LS controls with an AUC of 0.92 (0.83–1.0); the AUC for sporadic endometrial cancer versus sporadic controls was nominally higher, 0.99 (0.96–1.0).MDMs previously identified in sporadic endometrial cancer and colorectal cancer discriminate between endometrial cancer and benign endometrium and colorectal cancer and benign colorectum in LS. This supports the inclusion of patients with LS within future prospective clinical trials evaluating endometrial cancer and colorectal cancer MDMs and may provide a new avenue for cancer screening or surveillance in this high-risk population.Prevention Relevance:Lynch syndrome (LS) markedly increases risks of colorectal and endometrial cancers. Early detection biomarkers for LS cancers could reduce the needs for invasive screening and surgery. Methylated DNA markers previously identified in sporadic endometrial cancer and colorectal cancer discriminate between benign and cancer tissue in LS.
Metastatic Competency and Tumor Spheroid Formation Are Independent Cell States Governed by RB in Lung Adenocarcinoma
Authors: Freeburg Nelson F. , Peterson Nia , Ruiz Dain A. , Gladstein Amy C. , Feldser David M. 
Published: September 2023

Inactivation of the retinoblastoma (RB) tumor suppressor in lung adenocarcinoma is associated with the rapid acquisition of metastatic ability and the loss of lung cell lineage commitment. We previously showed that restoration of RB in advanced lung adenocarcinomas in the mouse was correlated with a decreased frequency of lineage decommitted tumors and overt metastases. To identify a causal relationship for RB and its role in reprogramming lineage commitment and reducing metastatic competency in lung adenocarcinoma, we developed multiple tumor spheroid forming lines where RB restoration could be achieved after characterization of the degree of each spheroid's lineage commitment and metastatic ability. Surprisingly, we discovered that RB inactivation dramatically promoted tumor spheroid forming potential in tumors that arise in the KrasLSL-G12D/+; p53flox/flox lung adenocarcinoma model. However, RB reactivation had no effect on the maintenance of tumor spheroid lines once established. In addition, we show that RB-deficient tumor spheroid lines are not uniformly metastatically competent but are equally likely to be nonmetastatic. Interestingly, unlike tumor spheroid maintenance, RB restoration could functionally revert metastatic tumor spheroids to a nonmetastatic cell state. Thus, strategies to reinstate RB pathway activity in lung cancer may reverse metastatic ability and have therapeutic potential. Finally, the acquisition of tumor spheroid forming potential reflects underlying cell state plasticity, which is often predictive of, or even conflated with metastatic ability. Our data support that each is a discrete cell state restricted by RB and question the suitability of tumor spheroid models for their predictive potential of advanced metastatic tumor cell states.

Significance:
Members of the RB pathway are frequently mutated in lung adenocarcinoma. We show that RB regulates cell state plasticity, tumor spheroid formation, and metastatic competency. Our data indicate that these are independent states where spheroid formation is distinct from metastatic competency. Thus, we caution against conflating spheroid formation and other signs of cell state plasticity with advanced metastatic cell states. Nevertheless, our work supports clinical strategies to reactivate RB pathways.
The Physiognomy of a Nation
Authors: Schwartz Stephanie 
Published: September 2023

Abstract
This essay revisits American Photographs, one of the most important photographic books of the 1930s. Containing two portfolios by Walker Evans and an essay by Lincoln Kirstein, the 1938 publication presents readers with eighty-seven photographs printed one per double-page spread. While critical studies of the book have focused on the sequential ordering of the photographs, and on the book's filmic qualities, this essay considers the book's other organizing principle: physiognomy. More specifically, focusing on Evans's decision to include three photographs that he made in Cuba into the book's first part, it attends to the processes of racialization organizing the book and producing America in the 1930s. Challenging canonical accounts of American Photographs and Depression-era documentary more broadly, this essay argues for a history of documentary that does not dispense with its modernism. The argument is not that modernism is still with us but that we need its repetitions.
Evaluating a Century of Progress on the Cognitive Science of Adjective Ordering
Authors: Dyer William , Torres Charles , Scontras Gregory , Futrell Richard 
Published: September 2023

AbstractThe literature on adjective ordering abounds with proposals meant to account for why certain adjectives appear before others in multi-adjective strings (e.g., the small brown box). However, these proposals have been developed and tested primarily in isolation and based on English; few researchers have looked at the combined performance of multiple factors in the determination of adjective order, and few have evaluated predictors across multiple languages. The current work approaches both of these objectives by using technologies and datasets from natural language processing to look at the combined performance of existing proposals across 32 languages. Comparing this performance with both random and idealized baselines, we show that the literature on adjective ordering has made significant meaningful progress across its many decades, but there remains quite a gap yet to be explained.