bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Treatment Strategy for Skull Base Reconstruction for Anterior Cranial Fossa Intra- and Extracranial Tumors
Authors: He Jianqing , Lu Jin , Zhang Feng , Chen Junhui , Wang Yuhai , Zhang Qingyun 
Published: November 2020

Abstract
Anterior cranial fossa intra- and extracranial tumors arise from the anterior cranial fossa and invade the orbit and nose. Anterior cranial fossa tumor resection and skull base reconstruction are challenging for neurosurgeons due to the complex anatomy, leakage of cerebrospinal fluid, and critical neurovasculature involvement. The authors report a case series of cranio-orbital communicating tumors and cranionasal-orbital communicating tumors. All patients underwent a modified Derome approach or transfrontal basal approach, and all tumor resections were satisfactory. Skull base reconstruction for small defects (<1.5 cm) can be performed with autogenous fascia, muscle, and fat. Large defects (≥1.5 cm) require autogenous fascia, muscle, and fat combined with osseous reconstruction (autogenous bone, titanium mesh, and polyetheretherketone). The techniques and treatments were successful, and only 1 patient experienced mild cerebrospinal fluid leak but no intracranial infection, pneumocrania or intracranial hemorrhage. Additionally, long-term follow-up demonstrated that the outcomes remain favorable. According to a literature review, this technique might be an alternative strategy for treating anterior cranial fossa intra- and extracranial tumors, and better skull base reconstruction can prevent many postoperative complications.
Outcomes of 350 Robotic-assisted Esophagectomies at a High-volume Cancer Center
Authors: Pointer David T. , Saeed Sabrina , Naffouje Samer A. , Mehta Rutika , Hoffe Sarah E. , Dineen Sean P. , Fleming Jason B. , Fontaine Jacques P. , Pimiento Jose M. 
Published: November 2020

Objective:
To evaluate perioperative and oncologic outcomes in our RAMIE cohort and compare outcomes with contemporary OE controls.

Summary of Background Data:
RAMIE has emerged as an alternative to traditional open or laparoscopic approaches. Described in all esophagectomy techniques, rapid adoption has been attributed to both enhanced visualization and technical dexterity.

Methods:
We retrospectively reviewed patients who underwent RAMIE for malignancy. Patient characteristics, perioperative outcomes, and survival were evaluated. For perioperative and oncologic outcome comparison, contemporary OE controls were propensity-score matched from NSQIP and NCDB databases.

Results:
We identified 350 patients who underwent RAMIE between 2010 and 2019. Median body mass index was 27.4, 32% demonstrated a Charlson Comorbidity Index >4. Nodal disease was identified in 50% of patients and 74% received neoadjuvant chemoradiotherapy. Mean operative time and blood loss were 425 minutes and 232 mL, respectively. Anastomotic leak occurred in 16% of patients, 2% required reoperation. Median LOS was 9 days, and 30-day mortality was 3%. A median of 21 nodes were dissected with 96% achieving an R0 resection. Median survival was 67.4 months. 222 RAMIE were matched 1:1 to the NSQIP OE control. RAMIE demonstrated decreased LOS (9 vs 10 days, P = 0.010) and reoperative rates (2.3 vs 12.2%, P = 0.001), longer operative time (427 vs 311 minutes, P = 0.001), and increased rate of pulmonary embolism (5.4% vs 0.9%, P = 0.007) in comparison to NSQIP cohort. There was no difference in leak rate or mortality. Three hundred forty-three RAMIE were matched to OE cohort from NCDB with no difference in median overall survival (63 vs 53 months; P = 0.130).

Conclusion:
In this largest reported institutional series, we demonstrate that RAMIE can be performed safely with excellent oncologic outcomes and decreased hospital stay when compared to the open approach.
An efficient distributed algorithm with application to COVID-19 data from heterogeneous clinical sites
Authors: Tong Jiayi , Luo Chongliang , Islam Md Nazmul , Sheils Natalie , Buresh John , Edmondson Mackenzie , Merkel Peter A. , Lautenbach Ebbing , Duan Rui , Chen Yong 
Published: November 2020

ABSTRACTObjectivesIntegrating electronic health records (EHR) data from several clinical sites offers great opportunities to improve estimation with a more general population compared to analyses based on a single clinical site. However, sharing patient-level data across sites is practically challenging due to concerns about maintaining patient privacy. The objective of this study is to develop a novel distributed algorithm to integrate heterogeneous EHR data from multiple clinical sites without sharing patient-level data.Materials and MethodsThe proposed distributed algorithm for binary regression can effectively account for between-site heterogeneity and is communication-efficient. Our method is built on a pairwise likelihood function in the extended Mantel-Haenszel regression, which is known to be statistically highly efficient. We construct a surrogate pairwise likelihood function through approximating the target pairwise likelihood by its surrogate. We show that the proposed surrogate pairwise likelihood leads to a consistent and asymptotically normal estimator by effective communication without sharing individual patient-level data. We study the empirical performance of the proposed method through a systematic simulation study and an application with data of 14,215 COVID-19 patients from 230 clinical sites at UnitedHealth Group Clinical Research Database.ResultsThe proposed method was shown to perform close to the gold standard approach under extensive simulation settings. When the event rate is <5%, the relative bias of the proposed estimator is 30% smaller than that of the meta-analysis estimator. The proposed method retained high accuracy across different sample sizes and event rates compared with meta-analysis. In the data evaluation, the proposed estimate has a relative bias <9% when the event rate is <1%, whereas the meta-analysis estimate has a relative bias at least 10% higher than that of the proposed method.ConclusionsOur simulation study and data application demonstrate that the proposed distributed algorithm provides an estimator that is robust to heterogeneity in event rates when effectively integrating data from multiple clinical sites. Our algorithm is therefore an effective alternative to both meta-analysis and existing distributed algorithms for modeling heterogeneous multi-site binary outcomes.
Resuming professional football (soccer) during the COVID-19 pandemic in a country with high infection rates: A prospective cohort study
Authors: Schumacher Yorck Olaf , Tabben Montassar , Hassoun Khalid , Al Marwani Asmaa , Al Hussain Ibrahim , Coyle Peter , Abbassi Ahmed Khellil , Ballan Hani Taleb , Al Kuwari Abdulaziz Jaham , Chamari Karim , Bahr Roald 
Published: November 2020

AbstractObjectivesThe risk of viral transmission associated with contact sports such as football (soccer) during the COVID-19 pandemic is unknown. The aim of this study was to describe the infective and immune status of professional football players, team staff and league officials over a truncated football season resumed at the height of the COVID-19 pandemic in a country with high infection rates and to investigate the clinical symptoms related to COVID-19 infection in professional football players.MethodsProspective cohort study of 1337 football players, staff and officials during a truncated football season (9 weeks) with a tailored infection control program based on preventive measures and regular SARS-CoV-2 PCR swab testing (every 3-5 days) combined with serology testing for immunity (every 4 weeks). Clinical symptoms in positive participants were recorded using a 26-item, Likert-scale-based scoring system.ResultsDuring the study period, 85 subjects returned positive (cycle threshold (cT)≤30) or reactive (30<cT<40) PCR tests, of which 36 were players. The infection rate was consistent with that of the general population during the same time period. More than half of infected subjects were asymptomatic, and the remaining had only mild symptoms with no one requiring hospitalization. Symptom severity was associated with lower cT values. Social contacts and family were the most common sources of infection, and no infection could be traced to training or matches. Of the 36 infected players, 15 presented positive serology during the study period.ConclusionFootball played outdoors involving close contact between athletes represents a limited risk for SARS-CoV-2 infection and severe illness when preventive measures are in place.
Optimizing Vaccine Allocation to Combat the COVID-19 Pandemic
Authors: Bertsimas Dimitris , Ivanhoe Joshua , Jacquillat Alexandre , Li Michael , Previero Alessandro , Lami Omar Skali , Bouardi Hamza Tazi 
Published: November 2020

AbstractThe outbreak of COVID-19 has spurred extensive research worldwide to develop a vaccine. However, when a vaccine becomes available, limited production and distribution capabilities will likely lead to another challenge: who to prioritize for vaccination to mitigate the near-end impact of the pandemic? To tackle that question, this paper first expands a state-of-the-art epidemiological model, called DELPHI, to capture the effects of vaccinations and the variability in mortality rates across subpopulations. It then integrates this predictive model into a prescriptive model to optimize vaccine allocation, formulated as a bilinear, non-convex optimization model. To solve it, this paper proposes a coordinate descent algorithm that iterates between optimizing vaccine allocations and simulating the dynamics of the pandemic. We implement the model and algorithm using real-world data in the United States. All else equal, the optimized vaccine allocation prioritizes states with a large number of projected cases and sub-populations facing higher risks (e.g., older ones). Ultimately, the optimized vaccine allocation can reduce the death toll of the pandemic by an estimated 10–25%, or 10,000–20,000 deaths over a three-month period in the United States alone.Highlights–This paper formulates an optimization model for vaccine allocation in response to the COVID-19 pandemic. This model, referred to as DELPHI–V–OPT, integrates a predictive epidemiological model into a prescriptive model to support the allocation of vaccines across geographic regions (e.g., US states) and across risk classes (e.g., age groups).–This paper develops a scalable coordinate descent algorithm to solve the DELPHI–V–OPT model. The proposed algorithm converges effectively and in short computational times. Therefore, the proposed approach can be implemented efficiently, and allows extensive sensitivity analyses for scenario planning and policy analysis.–Computational results demonstrate that optimized vaccine allocation strategies can curb the death toll of the COVID-19 pandemic by an estimated at 10–25%, or 10,000–20,000 deaths over a three-month period in the United States alone. These results highlight the critical role of vaccine allocation to combat the COVID-19 pandemic, in addition to vaccine design and vaccine production.
The expression ofPDCD1andCD274in T cells and macrophages correlated positively with COVID-19 severity
Authors: Gao Qianqian , Liu Shang , Ding Renpeng , Chen Huanyi , Dong Xuan , Xie Jiarui , Li Yijian , Chen Lei , Liu Huan , Mu Feng 
Published: November 2020

AbstractThe immune responses underlying the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unclear. To help understand the pathology of coronavirus disease 2019 (COVID-19) pandemics, public data were analyzed and the expression ofPDCD1(encoding PD-1) andCD274(encoding PD-L1) in T cells and macrophages were identified to correlate positively with COVID-19 severity.
Metagenomic profiling of host-associated bacteria from 8 datasets of the red algaPorphyra purpurea, with MetaPhlAn 3.0
Authors: Nousias Orestis , Montesanto Federica 
Published: November 2020

AbstractMicrobial communities play a fundamental role in the association with marine algae, in fact they are recognized to be actively involved in growth and morphogenesis.Porphyra purpureais a red algae commonly found in the intertidal zone with an high economical value, indeed several species belonging to the genusPorphyraare intensely cultivated in the Eastern Asian countries. Moreover,P. purpureais widely used as model species in different fields, mainly due to its peculiar life cycle. Despite of that, little is known about the microbial community associated to this species. Here we report the microbial-associated diversity ofP. purpureain four different localities (Ireland, Italy United Kingdom and USA) through the analysis of eight metagenomic datasets obtained from the publicly available metagenomic nucleotide database (https://www.ebi.ac.uk/ena/). The metagenomic datasets were quality controlled with FastQC version 0.11.8, pre-processed with Trimmomatic version 0.39 and analysed with Methaplan 3.0, with a reference database containing clade specific marker genes from ~ 99.500 bacterial genomes, following the pan-genome approach, in order to identify the putative bacterial taxonomies and their relative abundances. Furthermore, we compared the results to the 16S rRNA metagenomic analysis pipeline of MGnify database to evaluate the effectiveness of the two methods. Out of the 43 bacterial species identified with MetaPhlAn 3.0 only 5 were common with the MGnify results and from the 21 genera, only 9 were common. This approach highlighted the different taxonomical resolution of a 16S rRNA OTU-based method in contrast to the pan-genome approach deployed by MetaPhlAn 3.0.
Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the unfolded protein response (UPR) in models of neurodegeneration
Authors: Vidal René L. , Sepulveda Denisse , Troncoso-Escudero Paulina , Garcia-Huerta Paula , Gonzalez Constanza , Plate Lars , Jerez Carolina , Canovas José , Rivera Claudia A. , Castillo Valentina , Cisternas Marisol , Leal Sirley , Martinez Alexis , Grandjean Julia , Lashuel Hilal A. , Martin Alberto J.M. , Latapiat Veronica , Matus Soledad , Sardi S. Pablo , Wiseman R. Luke , Hetz Claudio 
Published: November 2020

AbstractAlteration to endoplasmic reticulum (ER) proteostasis is observed on a variety of neurodegenerative diseases associated with abnormal protein aggregation. Activation of the unfolded protein response (UPR) enables an adaptive reaction to recover ER proteostasis and cell function. The UPR is initiated by specialized stress sensors that engage gene expression programs through the concerted action of the transcription factors ATF4, ATF6f, and XBP1s. Although UPR signaling is generally studied as unique linear signaling branches, correlative evidence suggests that ATF6f and XBP1s may physically interact to regulate a subset of UPR-target genes. Here, we designed an ATF6f-XBP1s fusion protein termed UPRplus that behaves as a heterodimer in terms of its selective transcriptional activity. Cell-based studies demonstrated that UPRplus has stronger an effect in reducing the abnormal aggregation of mutant huntingtin and alpha-synuclein when compared to XBP1s or ATF6 alone. We developed a gene transfer approach to deliver UPRplus into the brain using adeno-associated viruses (AAVs) and demonstrated potent neuroprotectionin vivoin preclinical models of Parkinson’s and Huntington’s disease. These results support the concept where directing UPR-mediated gene expression toward specific adaptive programs may serve as a possible strategy to optimize the beneficial effects of the pathway in different disease conditions.
In-vitro virucidal activity of hypothiocyanite and hypothiocyanite/lactoferrin mix against SARS-CoV-2
Authors: Cegolon Luca , Mirandola Mattia , Salaris Claudio , Salvati Maria Vittoria , Salata Cristiano , Mastrangelo Giuseppe 
Published: November 2020

ABSTRACTSARS-CoV-2 replicates efficiently in the upper airway during prodromal stage with resulting viral shedding into the environment from patients with active disease as well as from asymptomatic individuals. So far, virus spread has been exclusively contained by non-pharmacological interventions (social distancing, face masks, hand washing and several measures limiting business activities or movement of individuals)1,2. There is a need to find pharmacological interventions to mitigate the viral spread, supporting yet limiting the existing health protection measures while an effective and safe vaccine will hopefully become available. Hypothiocyanite and lactoferrin as part of the innate human immune system were shown to have a large spectrum of cidal activity against bacteria, fungi and viruses2,3. To test their virucidal activity against SARS-CoV-2 we conducted an in-vitro study. Here we show a dose-dependent virucidal activity of hypothiocyanite at micromolar concentrations, slightly improved by the presence of lactoferrin. The two substances are devoid of any cytotoxicity and may be administered combined by aerosol to exploit their antiviral activity at the port of entry (mouth, nasal cavity, conjunctiva) or exit (mouth, through emission of respiratory droplets) of SARS-CoV-2 in the human body. Furthermore, aerosol with hypothiocyanite and lactoferrin combined could also have a therapeutic effect in the lower respiratory tract, at the level of gas exchange units of the lung, preventing the devastating infection of alveolar type II cells where ACE2 is highly expressed. An in-vivo validation of in-vitro results is urgently required.
Design to Data for mutants of β-glucosidase B fromPaenibacillus polymyxa:L171M, H178M, M221L, E406W, N160E, F415M
Authors: Huang Xiaoqing , Kim Daniel , Huang Peishan , Vater Ashley , Siegel Justin B. 
Published: November 2020

ABSTRACTComputational protein design is growing in popularity as a means to engineer enzymes. Currently, protein design algorithms can predict the stability and function of the enzymes to only a limited degree. Thus, further experimental data is required for training software to more accurately characterize the structure-function relationship of enzymes. To date, the Design2Data (D2D) database holds 129 single point mutations of β-glucosidase B (BglB) characterized by kinetic and thermal stability biophysical parameters. In this study, we introduced six mutants into the BglB database and examined their catalytic activity and thermal stability: L171M, H178M, M221L, E406W, N160E, and F415M.
Sequential ER stress and inflammatory responses are induced by SARS-CoV-2 ORF3 through ERphagy
Authors: Zhang Xiaolin , Yang Ziwei , Long Xubing , Sun Qinqin , Wang Fan , Wang Pei-hui , Li Xiaojuan , Kuang Ersheng 
Published: November 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have resulted in a number of severe cases of COVID-19 and deaths worldwide. However, knowledge of SARS-CoV-2 infection, diseases and therapy remains limited, underlining the urgency of fundamental studies and drug development. Studies have shown that induction of autophagy and hijacking of autophagic machinery are essential for infection and replication of SARS-CoV-2; however, the mechanism of this manipulation and function of autophagy during SARS-CoV-2 infection remain unclear. In the present study, we identified ORF3 as an inducer of autophagy and revealed that ORF3 localizes to the ER and induces FAM134B-related ERphagy through the HMGB1-Beclin1 pathway. As a consequence, ORF3 induces ER stress and inflammatory responses through ERphagy and sensitizes cells to ER stress-induced cell death, suggesting that SARS-CoV-2 ORF3 hijacks ERphagy and then harms ER homeostasis to induce inflammatory responses through excessive ER stress. These findings reveal a sequential induction of ERphagy, ER stress and acute inflammatory responses during SARS-CoV-2 infection and provide therapeutic potential for ERphagy and ER stress-related drugs for COVID-19 treatment and prevention.ImportanceSARS-CoV-2 infection and replication require autophagosome-like double-membrane vacuoles. Inhibition of autophagy suppresses viral replication, indicating the essential role of autophagy in SARS-CoV-2 infection. However, how SARS-CoV-2 hijacks autophagy and the function of autophagy in the disease progression remain unknown. Here, we reveal that SARS-CoV-2 ORF3 induces ERphagy and consequently induces ER stress to trigger acute inflammatory responses and enhance sensitivity to ER stress-induced apoptosis. Our studies uncover ERphagy-induced inflammatory responses during SARS-CoV-2 infection and provide a promising therapeutic approach for treating SARS-CoV-2 infection and inflammatory responses in COVID-19 by manipulating autophagy and ER stress.
A unique adhesive motif of protein disulfide isomerase P5 supports its function via dimerization
Authors: Okumura Masaki , Kanemura Shingo , Matsusaki Motonori , Kinoshita Misaki , Saio Tomohide , Ito Dai , Hirayama Chihiro , Kumeta Hiroyuki , Watabe Mai , Amagai Yuta , Lee Young-Ho , Akiyama Shuji , Inaba Kenji 
Published: November 2020

SUMMARYP5, also known as PDIA6, is a PDI-family member that plays an important role in the ER quality control. Herein, we revealed that P5 dimerizes via a unique adhesive motif contained in the N-terminal thioredoxin-like domain. This motif is apparently similar to, but radically different from conventional leucine-zipper motifs, in that the former includes a periodic repeat of leucine or valine residues at the third or fourth position spanning five helical turns on 15-residue anti-parallel α-helices, unlike the latter of which the leucine residues appear every two helical turns on ∼30-residue parallel α-helices at dimer interfaces. A monomeric P5 mutant with the impaired adhesive motif showed structural instability and local unfolding, and behaved as an aberrant protein that induces the ER stress response. Disassembly of P5 to monomers compromised its ability to inactivate IRE1α via reduction of intermolecular disulfide bonds and its Ca2+-dependent regulation of chaperone functionin vitro. Thus, the leucine-valine adhesive motif supports structure and physiological function of P5.
The impact of early public health interventions on SARS-CoV-2 transmission and evolution
Authors: Duchene Sebastian , Featherstone Leo , de Blasio Birgitte Freiesleben , Holmes Edward C. , Bohlin Jon , Pettersson John H.-O. 
Published: November 2020

AbstractBackgroundMany countries have attempted to mitigate and control COVID-19 through the implementation of non-pharmaceutical interventions, particularly with the aim of reducing population movement and contact. However, it remains unclear how the different control strategies impacted the local phylodynamics of the causative SARS-CoV-2 virus.AimTo assess the duration of chains of virus transmission within individual countries and the extent to which countries export viruses to their geographic neighbours.MethodsTo address core questions in genomic epidemiology and public health we analysed complete SARS-CoV-2 genomes to infer the relative frequencies of virus importation and exportation, as well as virus transmission dynamics, within countries of northern Europe. To this end, we examined virus evolution and phylodynamics in Denmark, Finland, Iceland, Norway and Sweden during the first year of the pandemic.ResultsThe Nordic countries differed markedly in the invasiveness of control strategies implemented. In particular, Sweden did not initially employ any strict population movement limitations and experienced markedly different transmission chain dynamics, which were more numerous and tended to have more cases, a set of features that increased with time during the first eight months of 2020.ConclusionTogether with Denmark, Sweden was also characterised as a net exporter of SARS-CoV-2. Hence, Sweden effectively constituted an epidemiological and evolutionary ‘refugia’ that enabled the virus to maintain active transmission and spread to other geographic localities. In sum, our analysis reveals the utility of genomic surveillance where active transmission chain monitoring is a key metric.