bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two contrasting papers stimulate a commentary on the origins of tumour immunology, current cancer immunotherapies, and the future potential for cancer immunotherapy
Authors: Bodmer Walter 
Published: December 2022

SummaryTwo early papers expressing conflicting views on the occurrence of effective immune attack against cancers stimulate an analysis of the gradual development of an understanding of tumour biology. This understanding has led to the development of the strikingly effective check point blocking and CART anti-cancer immunotherapies, and the promise of more widely applicable therapies based on T cell attracting genetically engineered monoclonal antibodies.
HN1L/AP-2γ/PLK1 signaling drives tumor progression and chemotherapy resistance in esophageal squamous cell carcinoma
Authors: Zeng Ting-Ting , Deng Tian-Hao , Liu Zhen , Zhan Jia-Rong , Ma Yuan-Zhen , Yan Yuan-Yuan , Sun Xiao , Zhu Ying-Hui , Li Yan , Guan Xin-Yuan , Li Lei 
Published: December 2022

AbstractHematological and neurological expressed 1 like (HN1L) is a newly identified oncogene in lung cancer and hepatocellular carcinoma recently identified by our team, but its roles in the development and treatment of esophageal squamous cell carcinoma (ESCC) remain incompletely cataloged. Here, using ESCC tissue array and public database analysis, we demonstrated that HN1L was highly expressed in ESCC tissues, which was associated with tumor tissue invasion, poor clinical stage and short survival for ESCC patients. Loss- and gain-of-function studies in ESCC cells revealed that HN1L enhances ESCC cell metastasis and proliferation in vitro and in mice models. Moreover, high level of HN1L reduces the sensibility of ESCC cells to chemotherapeutic drugs, such as Docetaxel. Mechanism studies revealed that HN1L activated the transcription of polo-like kinase 1 (PLK1) by interacting with transcription factor AP-2γ, which increased the expression of malignancy related proteins Cyclin D1 and Slug in ESCC cells. Blocking PLK1 with inhibitor BI-2356 abrogated the oncogenic function of HN1L and significantly suppressed ESCC progression by combining with chemotherapy. Therefore, this study demonstrates the vital pro-tumor role of HN1L/AP-2γ/PLK1 signaling axis in ESCC, offering a potential therapeutic strategy for ESCC patients with high HN1L by blocking PLK1.
Effect of trabeculectomy on the rate of progression of visual field damage
Authors: Koenig Susanna Friederike , Montesano Giovanni , Fang Clarissa Ern Hui , Crabb David Paul , Jayaram Hari , Clarke Jonathan 
Published: December 2022

Abstract
Objectives
This study quantifies the effect of trabeculectomy on the rate of progression (RoP) of visual field (VF) damage utilising pre- and post-operative visual function as the outcome instead of surrogate outcomes of success.

Methods
Clinical and VF data from 199 sequential patients who underwent trabeculectomy between 2015 and 2016 were extracted from the network of sites of Moorfields Eye Hospital NHS Foundation Trust. Of these, we analysed 80 eyes of 74 patients who met our inclusion criteria of at least three reliable VFs before and after surgery (false positive rate <15%). The change in mean RoP (dB/year) was tested using point-wise sensitivity values through a mixed effect model with random effects on both intercepts and slopes. A broken-stick regression of sensitivity over time, with a breakpoint at the day of surgery, modelled the individual change in RoP.

Results
We analysed 10 [9,12] VFs per subject (Median [Interquartile Range]). At surgery, the age was 67 [57, 72] years, mean deviation was −10.84 [−14.7, −5.6] dB and the IOP was 18 [15, 20] mmHg. One year after surgery, the IOP was 10 [8,13] mmHg (p = 0.002). Mean RoP before surgery was −0.94 [−1.20, −0.69] dB/year (Mean [95% credible intervals]) and it was slowed down by 0.62 [0.26, 0.97] dB/year (p < 0.001) after surgery.

Conclusions
Trabeculectomy leads to a significant reduction in the RoP of VF loss postoperatively.
Management of presumed trematode-induced granulomatous intermediate uveitis
Authors: Amin Rana Hussein , Abdullatif Abdussalam Mohsen 
Published: December 2022

Abstract
Purpose
To describe the surgical management of presumed trematode-induced granulomatous intermediate uveitis (PTIGIU) not responding to medical treatment in controlling the inflammation.

Methods
A prospective, interventional, single-center study in which patients with a history of fresh canal water contact and PTIGIU were enrolled. All patients underwent lensectomy–pars plana vitrectomy (PPV) and post-operative control of inflammation, functional and anatomical outcomes were assessed.

Results
Fifteen eyes of 12 patients were included in the study with median age of 11.6 ± 4 yrs. Six months following lensectomy-PPV, inflammation was well controlled in all patients. The eyes were divided into two groups: Group A: 10 patients with an attached retina while Group B: 5 patients who were in the cicatricial stage with tractional retinal detachment. All patients in group A had CDVA of 20/40 or better, unlike patients in group B who failed to achieve a CDVA better than 20/70 throughout their follow-up. In group B, final anatomical success was achieved in only 40% with hypotony occurring in 20%.

Conclusion
PTIGIU is associated with the presence of ciliary body granuloma which, if left untreated, can lead to drastic outcomes. Early lensectomy-PPV represents a viable management option in cases resistant to medical treatment, with a favorable outcome.
Organocatalyst-mediated five-pot synthesis of (–)-quinine
Authors: Terunuma Takahiro , Hayashi Yujiro 
Published: December 2022

AbstractIn this work, the enantioselective total synthesis of (–)-quinine has been accomplished in a pot-economical manner using five reaction vessels. In the first pot, reactions involve the diphenylprolinol silyl ether-mediated Michael reaction, aza-Henry reaction, hemiaminalization, and elimination of HNO2 (five reactions), affording a chiral tetrahydropyridine with excellent enantioselectivity. In the second pot, five reactions proceed with excellent diastereoselectivity to afford a trisubstituted piperidine with the desired stereochemistry. A further five reactions are carried out in the last one-pot sequence.
Breast cancer prevention by short-term inhibition of TGFβ signaling
Authors: Alečković Maša , Cristea Simona , Gil Del Alcazar Carlos R. , Yan Pengze , Ding Lina , Krop Ethan D. , Harper Nicholas W. , Rojas Jimenez Ernesto , Lu Donghao , Gulvady Anushree C. , Foidart Pierre , Seehawer Marco , Diciaccio Benedetto , Murphy Katherine C. , Pyrdol Jason , Anand Jayati , Garza Kodie , Wucherpfennig Kai W. , Tamimi Rulla M. , Michor Franziska , Polyak Kornelia 
Published: December 2022

AbstractCancer prevention has a profound impact on cancer-associated mortality and morbidity. We previously identified TGFβ signaling as a candidate regulator of mammary epithelial cells associated with breast cancer risk. Here, we show that short-term TGFBR inhibitor (TGFBRi) treatment of peripubertal ACI inbred and Sprague Dawley outbred rats induces lasting changes and prevents estrogen- and carcinogen-induced mammary tumors, respectively. We identify TGFBRi-responsive cell populations by single cell RNA-sequencing, including a unique epithelial subpopulation designated secretory basal cells (SBCs) with progenitor features. We detect SBCs in normal human breast tissues and find them to be associated with breast cancer risk. Interactome analysis identifies SBCs as the most interactive cell population and the main source of insulin-IGF signaling. Accordingly, inhibition of TGFBR and IGF1R decrease proliferation of organoid cultures. Our results reveal a critical role for TGFβ in regulating mammary epithelial cells relevant to breast cancer and serve as a proof-of-principle cancer prevention strategy.
pGlycoQuant with a deep residual network for quantitative glycoproteomics at intact glycopeptide level
Authors: Kong Siyuan , Gong Pengyun , Zeng Wen-Feng , Jiang Biyun , Hou Xinhang , Zhang Yang , Zhao Huanhuan , Liu Mingqi , Yan Guoquan , Zhou Xinwen , Qiao Xihua , Wu Mengxi , Yang Pengyuan , Liu Chao , Cao Weiqian 
Published: December 2022

AbstractLarge-scale intact glycopeptide identification has been advanced by software tools. However, tools for quantitative analysis remain lagging behind, which hinders exploring the differential site-specific glycosylation. Here, we report pGlycoQuant, a generic tool for both primary and tandem mass spectrometry-based intact glycopeptide quantitation. pGlycoQuant advances in glycopeptide matching through applying a deep learning model that reduces missing values by 19–89% compared with Byologic, MSFragger-Glyco, Skyline, and Proteome Discoverer, as well as a Match In Run algorithm for more glycopeptide coverage, greatly expanding the quantitative function of several widely used search engines, including pGlyco 2.0, pGlyco3, Byonic and MSFragger-Glyco. Further application of pGlycoQuant to the N-glycoproteomic study in three different metastatic HCC cell lines quantifies 6435 intact N-glycopeptides and, together with in vitro molecular biology experiments, illustrates site 979-core fucosylation of L1CAM as a potential regulator of HCC metastasis. We expected further applications of the freely available pGlycoQuant in glycoproteomic studies.
Quantifying the role of transcript levels in mediating DNA methylation effects on complex traits and diseases
Authors: Sadler Marie C. , Auwerx Chiara , Lepik Kaido , Porcu Eleonora , Kutalik Zoltán 
Published: December 2022

AbstractHigh-dimensional omics datasets provide valuable resources to determine the causal role of molecular traits in mediating the path from genotype to phenotype. Making use of molecular quantitative trait loci (QTL) and genome-wide association study (GWAS) summary statistics, we propose a multivariable Mendelian randomization (MVMR) framework to quantify the proportion of the impact of the DNA methylome (DNAm) on complex traits that is propagated through the assayed transcriptome. Evaluating 50 complex traits, we find that on average at least 28.3% (95% CI: [26.9%–29.8%]) of DNAm-to-trait effects are mediated through (typically multiple) transcripts in the cis-region. Several regulatory mechanisms are hypothesized, including methylation of the promoter probe cg10385390 (chr1:8’022’505) increasing the risk for inflammatory bowel disease by reducing PARK7 expression. The proposed integrative framework can be extended to other omics layers to identify causal molecular chains, providing a powerful tool to map and interpret GWAS signals.
An in silico method to assess antibody fragment polyreactivity
Authors: Harvey Edward P. , Shin Jung-Eun , Skiba Meredith A. , Nemeth Genevieve R. , Hurley Joseph D. , Wellner Alon , Shaw Ada Y. , Miranda Victor G. , Min Joseph K. , Liu Chang C. , Marks Debora S. , Kruse Andrew C. 
Published: December 2022

AbstractAntibodies are essential biological research tools and important therapeutic agents, but some exhibit non-specific binding to off-target proteins and other biomolecules. Such polyreactive antibodies compromise screening pipelines, lead to incorrect and irreproducible experimental results, and are generally intractable for clinical development. Here, we design a set of experiments using a diverse naïve synthetic camelid antibody fragment (nanobody) library to enable machine learning models to accurately assess polyreactivity from protein sequence (AUC > 0.8). Moreover, our models provide quantitative scoring metrics that predict the effect of amino acid substitutions on polyreactivity. We experimentally test our models’ performance on three independent nanobody scaffolds, where over 90% of predicted substitutions successfully reduced polyreactivity. Importantly, the models allow us to diminish the polyreactivity of an angiotensin II type I receptor antagonist nanobody, without compromising its functional properties. We provide a companion web-server that offers a straightforward means of predicting polyreactivity and polyreactivity-reducing mutations for any given nanobody sequence.
Multiregional single-cell dissection of tumor and immune cells reveals stable lock-and-key features in liver cancer
Authors: Ma Lichun , Heinrich Sophia , Wang Limin , Keggenhoff Friederike L. , Khatib Subreen , Forgues Marshonna , Kelly Michael , Hewitt Stephen M. , Saif Areeba , Hernandez Jonathan M. , Mabry Donna , Kloeckner Roman , Greten Tim F. , Chaisaingmongkol Jittiporn , Ruchirawat Mathuros , Marquardt Jens U. , Wang Xin Wei 
Published: December 2022

AbstractIntratumor heterogeneity may result from the evolution of tumor cells and their continuous interactions with the tumor microenvironment which collectively drives tumorigenesis. However, an appearance of cellular and molecular heterogeneity creates a challenge to define molecular features linked to tumor malignancy. Here we perform multiregional single-cell RNA sequencing (scRNA-seq) analysis of seven liver cancer patients (four hepatocellular carcinoma, HCC and three intrahepatic cholangiocarcinoma, iCCA). We identify cellular dynamics of malignant cells and their communication networks with tumor-associated immune cells, which are validated using additional scRNA-seq data of 25 HCC and 12 iCCA patients as a stable fingerprint embedded in a malignant ecosystem representing features of tumor aggressiveness. We further validate the top ligand-receptor interaction pairs (i.e., LGALS9-SLC1A5 and SPP1-PTGER4 between tumor cells and macrophages) associated with unique transcriptome in additional 542 HCC patients. Our study unveils stable molecular networks of malignant ecosystems, which may open a path for therapeutic exploration.
Decoupling of respiration rates and abundance in marine prokaryoplankton
Authors: Munson-McGee Jacob H. , Lindsay Melody R. , Sintes Eva , Brown Julia M. , D’Angelo Timothy , Brown Joe , Lubelczyk Laura C. , Tomko Paxton , Emerson David , Orcutt Beth N. , Poulton Nicole J. , Herndl Gerhard J. , Stepanauskas Ramunas 
Published: December 2022

AbstractThe ocean–atmosphere exchange of CO2 largely depends on the balance between marine microbial photosynthesis and respiration. Despite vast taxonomic and metabolic diversity among marine planktonic bacteria and archaea (prokaryoplankton)1–3, their respiration usually is measured in bulk and treated as a ‘black box’ in global biogeochemical models4; this limits the mechanistic understanding of the global carbon cycle. Here, using a technology for integrated phenotype analyses and genomic sequencing of individual microbial cells, we show that cell-specific respiration rates differ by more than 1,000× among prokaryoplankton genera. The majority of respiration was found to be performed by minority members of prokaryoplankton (including the Roseobacter cluster), whereas cells of the most prevalent lineages (including Pelagibacter and SAR86) had extremely low respiration rates. The decoupling of respiration rates from abundance among lineages, elevated counts of proteorhodopsin transcripts in Pelagibacter and SAR86 cells and elevated respiration of SAR86 at night indicate that proteorhodopsin-based phototrophy3,5–7 probably constitutes an important source of energy to prokaryoplankton and may increase growth efficiency. These findings suggest that the dependence of prokaryoplankton on respiration and remineralization of phytoplankton-derived organic carbon into CO2 for its energy demands and growth may be lower than commonly assumed and variable among lineages.
Particle filtration efficiency measured using sodium chloride and polystyrene latex sphere test methods
Authors: Sipkens Timothy A. , Corbin Joel C. , Oldershaw Andrew , Smallwood Gregory J. 
Published: December 2022

AbstractStandards governing face masks differ in the test methods used to determine sub-micron particle filtration efficiency (PFE), such that the meaning of PFE is not universal. Unifying the meaning of PFE requires data using these different test methods to drive improvements in standards. This simple data set provides the equivalence between two major test methods used to assess PFE: (1) a test method using a neutralized, polydisperse sodium chloride (NaCl) and (2) a test method using an unneutralized, “monodisperse” polystyrene latex sphere (PSL) aerosols. Measurements are made on over 5800 real-world medical masks, leading to the establishment of a relationship between these two kinds of PFE for these products.
A vector-agent approach to (spatiotemporal) movement modelling and reasoning
Authors: Rahimi Saeed , Moore Antoni B. , Whigham Peter A. 
Published: December 2022

AbstractModelling a complex system of autonomous individuals moving through space and time essentially entails understanding the (heterogeneous) spatiotemporal context, interactions with other individuals, their internal states and making any underlying causal interrelationships explicit, a task for which agents (including vector-agents) are specifically well-suited. Building on a conceptual model of agent space–time and reasoning behaviour, a design guideline for an implemented vector-agent model is presented. The movement of football players was chosen as it is appropriately constrained in space, time and individual actions. Sensitivity-variability analysis was applied to measure the performance of different configurations of system components on the emergent movement patterns. The model output varied more when the condition of the contextual actors (players’ role-areas) was manipulated. The current study shows how agent-based modelling can contribute to our understanding of movement and how causally relevant evidence can be produced, illustrated through a spatiotemporally constrained football case-study.
A GBD 2019 study of health and Sustainable Development Goal gains and forecasts to 2030 in Spain
Authors: Lazarus Jeffrey V. , Ortiz Alberto , Tyrovolas Stefanos , Fernández Esteve , Guy Danielle , White Trenton M. , Ma Rui , Hay Simon I. , Naghavi Mohsen , Soriano Joan B. ,   The GBD 2019 Spain Collaborators, García-Basteiro Alberto L. , Ayuso-Mateos Jose L. , Bassat Quique , Benavides Fernando G. , Giné-Vázquez Iago , Haro Josep Maria , Koyanagi Ai , Martinez-Raga Jose , Padron-Monedero Alicia , Peñalvo José L. , Pérez-Gómez Jorge , Rojas-Rueda David , Sarmiento-Suárez Rodrigo , Tabarés-Seisdedos Rafael 
Published: December 2022

AbstractThis study aimed to report mortality, risk factors, and burden of diseases in Spain. The Global Burden of Disease, Injuries, and Risk Factors 2019 estimates the burden due to 369 diseases, injuries, and impairments and 87 risk factors and risk factor combinations. Here, we detail the updated Spain 1990–2019 burden of disease estimates and project certain metrics up to 2030. In 2019, leading causes of death were ischaemic heart disease, stroke, chronic obstructive pulmonary disease, Alzheimer’s disease, and lung cancer. Main causes of disability adjusted life years (DALYs) were ischaemic heart disease, diabetes, lung cancer, low back pain, and stroke. Leading DALYs risk factors included smoking, high body mass index, and high fasting plasma glucose. Spain scored 74/100 among all health-related Sustainable Development Goals (SDGs) indicators, ranking 20 of 195 countries and territories. We forecasted that by 2030, Spain would outpace Japan, the United States, and the European Union. Behavioural risk factors, such as smoking and poor diet, and environmental factors added a significant burden to the Spanish population’s health in 2019. Monitoring these trends, particularly in light of COVID-19, is essential to prioritise interventions that will reduce the future burden of disease to meet population health and SDG commitments.
DrugRepo: a novel approach to repurposing drugs based on chemical and genomic features
Authors: Wang Yinyin , Aldahdooh Jehad , Hu Yingying , Yang Hongbin , Vähä-Koskela Markus , Tang Jing , Tanoli Ziaurrehman 
Published: December 2022

AbstractThe drug development process consumes 9–12 years and approximately one billion US dollars in costs. Due to the high finances and time costs required by the traditional drug discovery paradigm, repurposing old drugs to treat cancer and rare diseases is becoming popular. Computational approaches are mainly data-driven and involve a systematic analysis of different data types leading to the formulation of repurposing hypotheses. This study presents a novel scoring algorithm based on chemical and genomic data to repurpose drugs for 669 diseases from 22 groups, including various cancers, musculoskeletal, infections, cardiovascular, and skin diseases. The data types used to design the scoring algorithm are chemical structures, drug-target interactions (DTI), pathways, and disease-gene associations. The repurposed scoring algorithm is strengthened by integrating the most comprehensive manually curated datasets for each data type. At DrugRepo score ≥ 0.4, we repurposed 516 approved drugs across 545 diseases. Moreover, hundreds of novel predicted compounds can be matched with ongoing studies at clinical trials. Our analysis is supported by a web tool available at: http://drugrepo.org/.
Obesity is associated with early recurrence on breast cancer patients that achieved pathological complete response to neoadjuvant chemotherapy
Authors: Acevedo Francisco , Walbaum Benjamín , Muñiz Sabrina , Petric Militza , Martínez Raúl , Guerra Constanza , Navarro Marisel , Córdova-Delgado Miguel , Pinto Mauricio P. , Sánchez Cesar 
Published: December 2022

AbstractPathological complete response (pCR) after neoadjuvant chemotherapy (NCT) is associated with good long-term prognosis in breast cancer (BC) patients. However, some patients still recur and eventually die from this disease. For years, clinical stage at diagnosis has been consistently linked to recurrence and survival in the pCR setting. Herein, we aimed to identify other potential predictors of recurrence and survival in patients that achieved pCR. We performed a retrospective analysis of patients diagnosed between 2011 and 2020 in our center. We calculated overall survival (OS), invasive disease-free survival (IDFS), distant disease-free survival (DDFS), and BC-specific survival (BCSS). Among the 241 patients included into our study 36% were obese (Body Mass Index (BMI) > 29.9 kg/m2) and 47% were stage III. Multivariate analysis confirmed that obesity was a significant risk factor associated with early recurrence and poorer survival in these patients. In summary, obesity and clinical stage predict early recurrence and poorer survival in patients that achieved pCR after NCT. Pending further investigation and based on our findings we speculate that weight management could be beneficial for this subset of patients. To our knowledge, this is the first Latin American report linking obesity and recurrence within this setting.