bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of endoscopic vacuum therapy as rescue treatment in refractory leaks after gastro-esophageal surgery
Authors: De Pasqual Carlo Alberto , Mengardo Valentina , Tomba Francesco , Veltri Alessandro , Sacco Michele , Giacopuzzi Simone , Weindelmayer Jacopo , de Manzoni Giovanni 
Published: November 2020

AbstractThe treatment of leak after esophageal and gastric surgery is a major challenge. Over the last few years, endoscopic vacuum therapy (E-VAC) has gained popularity in the management of this life-threatening complication. We reported our initial experience on E-VAC therapy as rescue treatment in refractory anastomotic leak and perforation after gastro-esophageal surgery. From September 2017 to December 2019, a total of 8 E-VAC therapies were placed as secondary treatment in 7 patients. Six for anastomotic leak (3 cervical, 1 thoracic, 2 abdominal) and 1 for perforation of the gastric conduit. In 6 cases, E-VAC was placed intracavitary; while in the remaining 2, the sponge was positioned intraluminal (one patient was treated with both approaches). A total of 60 sponges were used in the whole cohort. The median number of sponge insertions was 10 (range: 5–14) with a median treatment duration of 41 days (range: 19–49). A complete healing was achieved in 4 intracavitary (67%) and in 1 intraluminal (50%) E-VAC. We observed only one E-VAC-related complication: a bleeding successfully managed endoscopically. E-VAC therapy seems to be a safe and effective tool in the management of leaks and perforations after upper GI surgery, although with longer healing time when it is used as secondary treatment.
The diversity of molecular mechanisms of carbonate biomineralization by bacteria
Authors: Görgen Sigrid , Benzerara Karim , Skouri-Panet Fériel , Gugger Muriel , Chauvat Franck , Cassier-Chauvat Corinne 
Published: November 2020

AbstractAlthough biomineralization of CaCO3is widespread in Bacteria and Archaea, the molecular mechanisms involved in this process remain less known than those used by Eukaryotes. A better understanding of these mechanisms is crucial for a broad diversity of studies including those (i) aiming at assessing the role of bacteria in the geochemical cycles of Ca and C, (ii) investigating the process of fossilization, and (iii) engineering applications using bacterially mediated CaCO3mineralization. Different types of bacterially-mediated mineralization modes have been distinguished depending on whether they are influenced (by extracellular organic molecules), induced (by metabolic activity) or controlled (by specific genes). In the first two types, mineralization is usually extracellular, while it is intracellular for the two ascertained cases of controlled bacterial mineralization. In this review, we list a large number of cases illustrating the three different modes of bacterially-mediated CaCO3mineralization. Overall, this shows the broad diversity of metabolic pathways, organic molecules and thereby microorganisms that can biomineralize CaCO3. Providing an improved understanding of the mechanisms involved and a good knowledge of the molecular drivers of carbonatogenesis, the increasing number of (meta)-omics studies may help in the future to estimate the significance of bacterially mediated CaCO3mineralization.
Treatment strategies for breast cancer brain metastases
Authors: Bailleux Caroline , Eberst Lauriane , Bachelot Thomas 
Published: November 2020

AbstractBrain metastases from breast cancer (BCBM) constitute the second most common cause of brain metastasis (BM), and the incidence of these frequently lethal lesions is currently increasing, following better systemic treatment. Patients with ER-negative and HER2-positive metastatic breast cancer (BC) are the most likely to develop BM, but if this diagnosis remains associated with a worse prognosis, long survival is now common for patients with HER2-positive BC. BCBM represents a therapeutic challenge that needs a coordinated treatment strategy along international guidelines. Surgery has always to be considered when feasible. It is now well established that stereotaxic radiosurgery allows for equivalent control and less-cognitive toxicities than whole-brain radiation therapy, which should be delayed as much as possible. Medical treatment for BCBM is currently a rapidly evolving field. It has been shown that the blood–brain barrier (BBB) is often impaired in macroscopic BM, and several chemotherapy regimens, antibody–drug conjugates and tyrosine-kinase inhibitors have been shown to be active on BCBM and can be part of the global treatment strategy. This paper provides an overview of the therapeutic option for BCBM that is currently available and outlines potential new approaches for tackling these deadly secondary tumours.
The COVID-19 pandemic and impact on breast cancer diagnoses: what happened in England in the first half of 2020
Authors: Gathani Toral , Clayton Gill , MacInnes Emma , Horgan Kieran 
Published: November 2020

AbstractDelays in cancer diagnosis and treatment due to the COVID-19 pandemic is a widespread source of concern, but the scale of the challenge for different tumour sites is not known. Routinely collected NHS England Cancer Waiting Time data were analysed to compare activity for breast cancer in the first 6 months of 2020 compared to the same time period in 2019. The number of referrals for suspected breast cancer was 28% lower (N = 231,765 versus N = 322,994), and the number of patients who received their first treatment for a breast cancer diagnosis was 16% lower (N = 19,965 versus N = 23,881). These data suggest that the number of breast cancers diagnosed during the first half of 2020 is not as low as initially feared, and a substantial proportion of the shortfall can be explained by the suspension of routine screening in March 2020. Further work is needed to examine in detail the impact of measures to manage the COVID-19 pandemic on breast cancer outcomes.
Prognostic impact of peripheral blood neutrophil to lymphocyte ratio in advanced-stage pulmonary large cell neuroendocrine carcinoma and its association with the immune-related tumour microenvironment
Authors: Shirasawa Masayuki , Yoshida Tatsuya , Horinouchi Hidehito , Kitano Shigehisa , Arakawa Sayaka , Matsumoto Yuji , Shinno Yuki , Okuma Yusuke , Goto Yasushi , Kanda Shintaro , Watanabe Reiko , Yamamoto Noboru , Watanabe Shun-ichi , Ohe Yuichiro , Motoi Noriko 
Published: November 2020

Abstract
Background
The prognostic value of the neutrophil-to-lymphocyte ratio (NLR) with large cell neuroendocrine carcinoma (LCNEC) patients remains unclear. Thus, we performed a retrospective study to examine the relationship between the pretreatment NLR and clinical outcome in advanced LCNEC patients and the impact of the immune-related tumour microenvironment (TME).

Methods
This retrospective study included 63 advanced LCNEC patients who had received chemotherapy. We collected clinical data and investigated the TME status (CD4, CD8, CD20 and FOXP3).

Results
The overall survival of the patients with a low NLR (<5) was significantly longer than those with a high NLR (≥5) (14.9 vs. 5.2 months; p < 0.001). A multivariate analysis identified a high NLR as a predictor of a poor prognosis (HR, 3.43; 95% CI, 1.73–6.79; p < 0.001). The NLR was inversely correlated with tumoural and stromal CD8-positive tumour-infiltrating lymphocytes (tumoural: r = −0.648, p = 0.005, stromal: r = −0.490, p = 0.046).

Conclusions
A high NLR was associated with a poor prognosis in advanced LCNEC patients. Our study revealed that the NLR can reflect the TME, at least in part, suggesting that the NLR plays an important role not only as a clinical outcome predictor but also as a tumour immune status indicator.
Identification and functional characterization of new missense SNPs in the coding region of the TP53 gene
Authors: Doffe Flora , Carbonnier Vincent , Tissier Manon , Leroy Bernard , Martins Isabelle , Mattsson Johanna S. M. , Micke Patrick , Pavlova Sarka , Pospisilova Sarka , Smardova Jana , Joerger Andreas C. , Wiman Klas G. , Kroemer Guido , Soussi Thierry 
Published: November 2020

AbstractInfrequent and rare genetic variants in the human population vastly outnumber common ones. Although they may contribute significantly to the genetic basis of a disease, these seldom-encountered variants may also be miss-identified as pathogenic if no correct references are available. Somatic and germline TP53 variants are associated with multiple neoplastic diseases, and thus have come to serve as a paradigm for genetic analyses in this setting. We searched 14 independent, globally distributed datasets and recovered TP53 SNPs from 202,767 cancer-free individuals. In our analyses, 19 new missense TP53 SNPs, including five novel variants specific to the Asian population, were recurrently identified in multiple datasets. Using a combination of in silico, functional, structural, and genetic approaches, we showed that none of these variants displayed loss of function compared to the normal TP53 gene. In addition, classification using ACMG criteria suggested that they are all benign. Considered together, our data reveal that the TP53 coding region shows far more polymorphism than previously thought and present high ethnic diversity. They furthermore underline the importance of correctly assessing novel variants in all variant-calling pipelines associated with genetic diagnoses for cancer.
Long-read trio sequencing of individuals with unsolved intellectual disability
Authors: Pauper Marc , Kucuk Erdi , Wenger Aaron M. , Chakraborty Shreyasee , Baybayan Primo , Kwint Michael , van der Sanden Bart , Nelen Marcel R. , Derks Ronny , Brunner Han G. , Hoischen Alexander , Vissers Lisenka E. L. M. , Gilissen Christian 
Published: November 2020

AbstractLong-read sequencing (LRS) has the potential to comprehensively identify all medically relevant genome variation, including variation commonly missed by short-read sequencing (SRS) approaches. To determine this potential, we performed LRS around 15×–40× genome coverage using the Pacific Biosciences Sequel I System for five trios. The respective probands were diagnosed with intellectual disability (ID) whose etiology remained unresolved after SRS exomes and genomes. Systematic assessment of LRS coverage showed that ~35 Mb of the human reference genome was only accessible by LRS and not SRS. Genome-wide structural variant (SV) calling yielded on average 28,292 SV calls per individual, totaling 12.9 Mb of sequence. Trio-based analyses which allowed to study segregation, showed concordance for up to 95% of these SV calls across the genome, and 80% of the LRS SV calls were not identified by SRS. De novo mutation analysis did not identify any de novo SVs, confirming that these are rare events. Because of high sequence coverage, we were also able to call single nucleotide substitutions. On average, we identified 3 million substitutions per genome, with a Mendelian inheritance concordance of up to 97%. Of these, ~100,000 were located in the ~35 Mb of the genome that was only captured by LRS. Moreover, these variants affected the coding sequence of 64 genes, including 32 known Mendelian disease genes. Our data show the potential added value of LRS compared to SRS for identifying medically relevant genome variation.
Bayesian learning of chemisorption for bridging the complexity of electronic descriptors
Authors: Wang Siwen , Pillai Hemanth Somarajan , Xin Hongliang 
Published: November 2020

AbstractBuilding upon the d-band reactivity theory in surface chemistry and catalysis, we develop a Bayesian learning approach to probing chemisorption processes at atomically tailored metal sites. With representative species, e.g., *O and *OH, Bayesian models trained with ab initio adsorption properties of transition metals predict site reactivity at a diverse range of intermetallics and near-surface alloys while naturally providing uncertainty quantification from posterior sampling. More importantly, this conceptual framework sheds light on the orbitalwise nature of chemical bonding at adsorption sites with d-states characteristics ranging from bulk-like semi-elliptic bands to free-atom-like discrete energy levels, bridging the complexity of electronic descriptors for the prediction of novel catalytic materials.
A clinically applicable deep-learning model for detecting intracranial aneurysm in computed tomography angiography images
Authors: Shi Zhao , Miao Chongchang , Schoepf U. Joseph , Savage Rock H. , Dargis Danielle M. , Pan Chengwei , Chai Xue , Li Xiu Li , Xia Shuang , Zhang Xin , Gu Yan , Zhang Yonggang , Hu Bin , Xu Wenda , Zhou Changsheng , Luo Song , Wang Hao , Mao Li , Liang Kongming , Wen Lili , Zhou Longjiang , Yu Yizhou , Lu Guang Ming , Zhang Long Jiang 
Published: November 2020

AbstractIntracranial aneurysm is a common life-threatening disease. Computed tomography angiography is recommended as the standard diagnosis tool; yet, interpretation can be time-consuming and challenging. We present a specific deep-learning-based model trained on 1,177 digital subtraction angiography verified bone-removal computed tomography angiography cases. The model has good tolerance to image quality and is tested with different manufacturers. Simulated real-world studies are conducted in consecutive internal and external cohorts, in which it achieves an improved patient-level sensitivity and lesion-level sensitivity compared to that of radiologists and expert neurosurgeons. A specific cohort of suspected acute ischemic stroke is employed and it is found that 99.0% predicted-negative cases can be trusted with high confidence, leading to a potential reduction in human workload. A prospective study is warranted to determine whether the algorithm could improve patients’ care in comparison to clinicians’ assessment.
A new view on the origin of zero-bias anomalies of Co atoms atop noble metal surfaces
Authors: Bouaziz Juba , Mendes Guimarães Filipe Souza , Lounis Samir 
Published: November 2020

AbstractMany-body phenomena are paramount in physics. In condensed matter, their hallmark is considerable on a wide range of material characteristics spanning electronic, magnetic, thermodynamic and transport properties. They potentially imprint non-trivial signatures in spectroscopic measurements, such as those assigned to Kondo, excitonic and polaronic features, whose emergence depends on the involved degrees of freedom. Here, we address systematically zero-bias anomalies detected by scanning tunneling spectroscopy on Co atoms deposited on Cu, Ag and Au(111) substrates, which remarkably are almost identical to those obtained from first-principles. These features originate from gaped spin-excitations induced by a finite magnetic anisotropy energy, in contrast to the usual widespread interpretation relating them to Kondo resonances. Resting on relativistic time-dependent density functional and many-body perturbation theories, we furthermore unveil a new many-body feature, the spinaron, resulting from the interaction of electrons and spin-excitations localizing electronic states in a well defined energy.
Epigenome-wide meta-analysis of DNA methylation differences in prefrontal cortex implicates the immune processes in Alzheimer’s disease
Authors: Zhang Lanyu , Silva Tiago C. , Young Juan I. , Gomez Lissette , Schmidt Michael A. , Hamilton-Nelson Kara L. , Kunkle Brian W. , Chen Xi , Martin Eden R. , Wang Lily 
Published: November 2020

AbstractDNA methylation differences in Alzheimer’s disease (AD) have been reported. Here, we conducted a meta-analysis of more than 1000 prefrontal cortex brain samples to prioritize the most consistent methylation differences in multiple cohorts. Using a uniform analysis pipeline, we identified 3751 CpGs and 119 differentially methylated regions (DMRs) significantly associated with Braak stage. Our analysis identified differentially methylated genes such asMAMSTR,AGAP2, andAZU1. The most significant DMR identified is located on theMAMSTRgene, which encodes a cofactor that stimulates MEF2C. Notably, MEF2C cooperates with another transcription factor, PU.1, a central hub in the AD gene network. Our enrichment analysis highlighted the potential roles of the immune system and polycomb repressive complex 2 in pathological AD. These results may help facilitate future mechanistic and biomarker discovery studies in AD.
Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform
Authors: Chiuppesi Flavia , Salazar Marcela d’Alincourt , Contreras Heidi , Nguyen Vu H. , Martinez Joy , Park Yoonsuh , Nguyen Jenny , Kha Mindy , Iniguez Angelina , Zhou Qiao , Kaltcheva Teodora , Levytskyy Roman , Ebelt Nancy D. , Kang Tae Hyuk , Wu Xiwei , Rogers Thomas F. , Manuel Edwin R. , Shostak Yuriy , Diamond Don J. , Wussow Felix 
Published: November 2020

AbstractModified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We demonstrate the construction of a vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we use this vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. We show that mice immunized with these sMVA vectors develop robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.
Lethality of SARS-CoV-2 infection in K18 human angiotensin-converting enzyme 2 transgenic mice
Authors: Oladunni Fatai S. , Park Jun-Gyu , Pino Paula A. , Gonzalez Olga , Akhter Anwari , Allué-Guardia Anna , Olmo-Fontánez Angélica , Gautam Shalini , Garcia-Vilanova Andreu , Ye Chengjin , Chiem Kevin , Headley Colwyn , Dwivedi Varun , Parodi Laura M. , Alfson Kendra J. , Staples Hilary M. , Schami Alyssa , Garcia Juan I. , Whigham Alison , Platt Roy Neal , Gazi Michal , Martinez Jesse , Chuba Colin , Earley Stephanie , Rodriguez Oscar H. , Mdaki Stephanie Davis , Kavelish Katrina N. , Escalona Renee , Hallam Cory R. A. , Christie Corbett , Patterson Jean L. , Anderson Tim J. C. , Carrion Ricardo , Dick Edward J. , Hall-Ursone Shannan , Schlesinger Larry S. , Alvarez Xavier , Kaushal Deepak , Giavedoni Luis D. , Turner Joanne , Martinez-Sobrido Luis , Torrelles Jordi B. 
Published: November 2020

AbstractVaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease would benefit from validated small animal models. Here, we show that transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2 transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2 transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 6. K18 hACE2 transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.
Edge-oriented and steerable hyperbolic polaritons in anisotropic van der Waals nanocavities
Authors: Dai Zhigao , Hu Guangwei , Si Guangyuan , Ou Qingdong , Zhang Qing , Balendhran Sivacarendran , Rahman Fahmida , Zhang Bao Yue , Ou Jian Zhen , Li Guogang , Alù Andrea , Qiu Cheng-Wei , Bao Qiaoliang 
Published: November 2020

AbstractHighly confined and low-loss polaritons are known to propagate isotropically over graphene and hexagonal boron nitride in the plane, leaving limited degrees of freedom in manipulating light at the nanoscale. The emerging family of biaxial van der Waals materials, such as α-MoO3 and V2O5, support exotic polariton propagation, as their auxiliary optical axis is in the plane. Here, exploiting this strong in-plane anisotropy, we report edge-tailored hyperbolic polaritons in patterned α-MoO3 nanocavities via real-space nanoimaging. We find that the angle between the edge orientation and the crystallographic direction significantly affects the optical response, and can serve as a key tuning parameter in tailoring the polaritonic patterns. By shaping α-MoO3 nanocavities with different geometries, we observe edge-oriented and steerable hyperbolic polaritons as well as forbidden zones where the polaritons detour. The lifetime and figure of merit of the hyperbolic polaritons can be regulated by the edge aspect ratio of nanocavity.
Depletion of circulating IgM memory B cells predicts unfavourable outcome in COVID-19
Authors: Lenti Marco Vincenzo , Aronico Nicola , Pellegrino Ivan , Boveri Emanuela , Giuffrida Paolo , Borrelli de Andreis Federica , Morbini Patrizia , Vanelli Laura , Pasini Alessandra , Ubezio Cristina , Melazzini Federica , Rascaroli Alessandro , Antoci Valentina , Merli Stefania , Di Terlizzi Francesco , Sabatini Umberto , Cambiè Ginevra , Tenore Annamaria , Picone Cristina , Vanoli Alessandro , Arcaini Luca , Baldanti Fausto , Paulli Marco , Corazza Gino Roberto , Di Sabatino Antonio 
Published: November 2020

AbstractImpaired immune responses have been hypothesised to be a possible trigger of unfavourable outcomes in coronavirus disease 2019 (COVID-19). We aimed to characterise IgM memory B cells in patients with COVID-19 admitted to an internal medicine ward in Northern Italy. Overall, 66 COVID-19 patients (mean age 74 ± 16.6 years; 29 females) were enrolled. Three patients (4.5%; 1 female) had been splenectomised and were excluded from further analyses. Fifty-five patients (87.3%) had IgM memory B cell depletion, and 18 (28.6%) died during hospitalisation (cumulative incidence rate 9.26/100 person-week; 5.8–14.7 95% CI). All patients who died had IgM memory B cell depletion. A superimposed infection was found in 6 patients (9.5%), all of them having IgM memory B cell depletion (cumulative incidence rate 3.08/100 person-week; 1.3–6.8 95% CI). At bivariable analyses, older age, sex, number of comorbidities, and peripheral blood lymphocyte count < 1500/µl were not correlated with IgM memory B cell depletion. A discrete-to-marked reduction of the B-cell compartment was also noticed in autoptic spleen specimens of two COVID-19 patients. We conclude that IgM memory B cells are commonly depleted in COVID-19 patients and this correlates with increased mortality and superimposed infections.