bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative 18F-FDG SUVmax >6.3 or Size >2.3 cm of primary lesions predict lymph nodes metastasis with higher negative predictive value in peripheral cT1 non-small-cell lung cancer
Authors: Li Xiao-Feng , Shi Yun-Mei , Niu Rong , Yang Yan-Song , Shao Xiao-Nan , Wang Jian-Feng , Shao Xiao-Liang , Zhang Fei-Fei , Xue Xiu-Qing , Wang Yue-Tao 
Published: July 2021

Background
Sublobar resection is suitable for peripheral cT1N0M0 non-small-cell lung cancer (NSCLC). The traditional PET-CT criterion (lymph node size ≥1.0 cm or SUVmax ≥2.5) for predicting lymph nodes metastasis (LNM) has unsatisfactory performance.

Objective
We explore the clinical role of preoperative SUVmax and the size of the primary lesions for predicting peripheral cT1 NSCLC LNM.

Methods
We retrospectively analyzed 174 peripheral cT1 NSCLC patients underwent preoperative 18F-FDG PET-CT and divided into the LNM and non-LNM group by pathology. We compared the differences of primary lesions’ baseline characteristics between the two groups. The risk factors of LNM were determined by univariate and multivariate analysis, and we assessed the diagnostic efficacy with the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value and negative predictive value (NPV).

Results
Of the enrolled cases, the incidence of LNM was 24.7%. The preoperative SUVmax >6.3 or size >2.3 cm of the primary lesions were independent risk factors of peripheral cT1 NSCLC LNM (ORs, 95% CIs were 6.18 (2.40–15.92) and 3.03 (1.35–6.81). The sensitivity, NPV of SUVmax >6.3 or size >2.3 cm of the primary lesions were higher than the traditional PET-CT criterion for predicting LNM (100.0 vs. 86.0%, 100.0 vs. 89.7%). A Hosmer–Lemeshow test showed a goodness-of-fit (P = 0.479).

Conclusions
The excellent sensitivity and NPV of preoperative of the SUVmax >6.3 or size >2.3 cm of the primary lesions based on 18F-FDG PET-CT might identify the patients at low-risk LNM in peripheral cT1 NSCLC.
Through Their Eyes
Authors: Moore Riley , Hayward Alexandra , Necaise Kellee 
Published: July 2021

Background:
Personal protective equipment (PPE) plays a critical role in protecting health care workers (HCWs). During the coronavirus disease-2019 (COVID-19) pandemic, shortages of PPE supplies drastically changed the way PPE was obtained and used by HCWs.

Purpose:
The objective was to investigate the impact of the COVID-19 pandemic and patient isolation type on PPE compliance.

Methods:
This investigation was a survey of HCWs at a level 1 trauma teaching hospital regarding PPE compliance patterns prior to and during the COVID-19 pandemic.

Results:
HCWs reported an increase in PPE compliance during the COVID-19 pandemic. Nearly half (48.6%) of respondents reported that isolation type impacted the decision to wear PPE, of which most were likely to forgo PPE with contact precautions.

Conclusions:
HCWs identified multiple barriers to compliance. The underutilization of PPE with contact precautions suggests that the risk of exposure is interpreted as low, and this could be a future target of education.
Parental Perspectives on Children's Functional Experiences After Limb Fracture
Authors: Golden-Plotnik Stevi , Ali Samina , Moir Mackenzie , Drendel Amy L. , Poonai Naveen , van Manen Michael 
Published: July 2021

Background
Fractures are a common childhood injury. Although the pain associated with fractures is well described, the related functional impact is less understood. When a child's function is impaired, his or her ability to participate in day-to-day life is restricted. Eighty percent of children with fractures experience compromise in daily function. An in-depth understanding of function can guide emergency department (ED) providers' discharge instructions.

Objectives
Our aim was to report caregivers' perspectives of the functional impact of limb fractures on their children's day-to-day life activities.

Methods
We performed a qualitative study using interviews of caregivers of children (aged 5 to 11 years) who received care for acute, nonoperative long bone fractures in a pediatric ED. Audio-recorded, semistructured telephone interviews were completed 7 to 14 days after the ED visit. Interviews were primarily open ended, including questions targeting areas of function from existing pediatric fracture literature. Qualitative analysis was completed using content analysis.

Results
Twenty-five interviews were included in the final analysis. Most of the children were diagnosed with upper extremity fractures, and most participants were mothers. All parents reported a change in their child's function. The most commonly affected areas were sleep, activities of daily living, and play. Play was either self-limited by the child or restricted by the parent. Pain was worse in the first days after discharge. Many children struggled emotionally with functional limitations. All children required help from their parents to perform daily tasks; this required adaptive strategies such as planning, changes to household routine, and missed work. Key concerns from parents included regression in the child's independence and fracture healing and complications.

Conclusions
Function is universally impaired in young children with fractures, significantly affecting family life after discharge. Discharge conversations with families should include pain management, changes to activities of daily living, family routines and play, and expectations for fracture healing.
A new sensitive and robust next-generation sequencing platform for HIV-1 drug resistance mutations testing
Authors: Yu Bin , Jin Changzhong , Ma Zixuan , Cai Ziwei , Li Tingsen , Wang Dan , Xiao Wenwen , Zheng Yanghao , Yin Wanpeng , Wu Nanping , Jiang Miao 
Published: July 2021

AbstractNext-generation sequencing (NGS) is a trending new platform which allows cheap, quantitative, high-throughput, parallel sequencing for minority variants with frequencies less than 20% of the HIV-1 quasi-species. In clinical setting, these advantages are crucial for choosing antiretroviral drugs with low genetic barriers and will potentially benefit treatment outcomes.In this investigation, we implemented the Boxin HIV-1 NGS platform for genotyping the drug-resistance-associated variants in PR/RT regions. Plasmids with known mutations were used to analyze the accuracy, reproducibility, and reliability of the Boxin NGS assay. Variant frequencies reported by Boxin NGS and the theoretical value were highly concordant. The Bland-Altman plot and the coefficient of variation (7%) suggested that the method has excellent reproducibility and reliability. Sanger sequencing confirmed the existence of these known variants with frequencies equal or above 20%.78 blood samples were obtained from AIDS patients and underwent PR/RT region genotyping by Sanger sequencing and Boxin NGS. 33 additional drug resistance mutations were identified by Boxin NGS, 23/33 mutations were minority variants with frequencies below 20%.15 blood samples obtained from AIDS patients underwent PR/RT region genotyping by Sanger sequencing, Boxin NGS, and Vela NGS. The Bland-Altman plot suggested that the variant frequencies detected by Boxin and Vela were highly concordant. Moreover, Boxin NGS assay detected five more minority variants with frequencies ranged from 1% to 20%. In a series of samples collected from 2016 to 2017, Boxin NGS reported a M184V mutation with a frequency of 4.92%, 3 months earlier than this mutation was firstly detected by Vela NGS and Sanger sequencing.In conclusion, Boxin NGS had good accuracy, reproducibility, and reliability. Boxin NGS was highly concordant with Sanger sequencing and Vela NGS. In terms of genotyping HIV-1 variants in PR/RT regions, Boxin NGS was more cost-efficient and appeared to have increased sensitivity without compromising sequence accuracy.
Association between the COVID-19 pandemic and pertussis in France using multiple nationwide data sources
Authors: Matczak Soraya , Levy Corinne , Fortas Camille , Cohen Jérémie F. , Béchet Stéphane , El Belghiti Fatima Aït , Guillot Sophie , Trombert-Paolantoni Sabine , Jacomo Véronique , Savitch Yann , Paireau Juliette , Brisse Sylvain , Guiso Nicole , Lévy-Bruhl Daniel , Cohen Robert , Toubiana Julie 
Published: July 2021

ABSTRACTBackgroundInterventions to mitigate coronavirus disease 19 (COVID-19) pandemic may impact other respiratory diseases such as pertussis. We aimed to study the course of pertussis in France over an 8-year period and its association with COVID-19 mitigation strategies, using multiple nationwide data sources.MethodsWe analyzed the number of French pertussis cases between 2013 and 2020, using the PCR test results from nationwide outpatient laboratories (Source 1) and the pediatric network of 41 hospitals (Source 2), and using the reports of an office-based pediatric national network (Source 3). We conducted a quasi-experimental interrupted time-series analysis, relying on negative binomial regression models. The models accounted for seasonality, long-term cycles, and secular trend, and included a binary variable for the first national lockdown (ordered on March 16, 2021).ResultsWe identified 19,039 cases of pertussis from the three data sources during the study period. There was a significant decrease of pertussis cases following the implementation of mitigation measures, with adjusted incidence rate ratios of 0.102 (95% CI 0.040-0.256) and 0.216 (95% CI 0.071-0.656) for Source 1 and Source 2, respectively. The association was confirmed in Source 3 (median of 1 [IQR 0-2] vs. 0 [IQR 0-0] pertussis cases per month before and after lockdown, respectively, p=0.0048).ConclusionThe drastic reduction of outpatient and hospitalized cases of pertussis strongly suggests an impact of COVID-19 mitigation measures and their consequences on pertussis epidemiology. Pertussis vaccination recommendations should be carefully followed, and disease monitoring should be continued to detect any resurgence after relaxation of mitigation measures.FundingThere was no specific funding for the study.
High frequency, high throughput quantification of SARS-CoV-2 RNA in wastewater settled solids at eight publicly owned treatment works in Northern California shows strong association with COVID-19 incidence
Authors: Wolfe Marlene K. , Topol Aaron , Knudson Alisha , Simpson Adrian , White Bradley , Vugia Duc J. , Yu Alexander T. , Li Linlin , Balliet Michael , Stoddard Pamela , Han George S. , Wigginton Krista R. , Boehm Alexandria B. 
Published: July 2021

AbstractA number of recent retrospective studies have demonstrated that SARS-CoV-2 RNA concentrations in wastewater are associated with COVID-19 cases in the corresponding sewersheds. Implementing high-resolution, prospective efforts across multiple plants depends on sensitive measurements that are representative of COVID-19 cases, scalable for high throughput analysis, and comparable across laboratories. We conducted a prospective study across eight publicly owned treatment works (POTWs). A focus on SARS-CoV-2 RNA in solids enabled us to scale-up our measurements with a commercial lab partner. Samples were collected daily and results were posted to a website within 24-hours. SARS-CoV-2 RNA in daily samples correlated to incidence COVID-19 cases in the sewersheds; a 1 log10 increase in SARS-CoV-2 RNA in settled solids corresponds to a 0.58 log10 (4X) increase in sewershed incidence rate. SARS-CoV-2 RNA signals measured with the commercial laboratory partner were comparable across plants and to measurements conducted in a university laboratory when normalized by pepper mild mottle virus PMMoV RNA. Results suggest that SARS-CoV-2 RNA should be detectable in settled solids for COVID-19 incidence rates > 1/100,000 (range 0.8 - 2.3 cases per 100,000). These sensitive, representative, scalable, and comparable methods will be valuable for future efforts to scale-up wastewater-based epidemiology.ImportanceAccess to reliable, rapid monitoring data is critical to guide response to an infectious disease outbreak. For pathogens that are shed in feces or urine, monitoring wastewater can provide a cost-effective snapshot of transmission in an entire community via a single sample. In order for a method to be useful for ongoing COVID-19 monitoring, it should be sensitive for detection of low concentrations of SARS-CoV-2, representative of incidence rates in the community, scalable to generate data quickly, and comparable across laboratories. This paper presents a method utilizing wastewater solids to meet these goals, producing measurements of SARS-CoV-2 RNA strongly associated with COVID-19 cases in the sewershed of a publicly owned treatment work. Results, provided within 24 hrs, can be used to detect incidence rates as low as approximately 1/100,000 cases and can be normalized for comparison across locations generating data using different methods.
One mucosal administration of a live attenuated recombinant COVID-19 vaccine protects nonhuman primates from SARS-CoV-2
Authors: Tioni Mariana F. , Jordan Robert , Pena Angie Silva , Garg Aditya , Wu Danlu , Phan Shannon I. , Cheng Xing , Greenhouse Jack , Orekov Tatyana , Valentin Daniel , Kar Swagata , Pessaint Laurent , Andersen Hanne , Stobart Christopher C. , Bloodworth Melissa H. , Peebles R. Stokes , Liu Yang , Xie Xuping , Shi Pei-Yong , Moore Martin L. , Tang Roderick S. 
Published: July 2021

AbstractSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 global pandemic. SARS-CoV-2 is an enveloped RNA virus that relies on its trimeric surface glycoprotein, spike, for entry into host cells. Here we describe the COVID-19 vaccine candidate MV-014-212, a live attenuated, recombinant human respiratory syncytial virus (RSV) expressing a chimeric SARS-CoV-2 spike as the only viral envelope protein. MV-014-212 was attenuated and immunogenic in African green monkeys (AGMs). One mucosal administration of MV-014-212 in AGMs protected against SARS-CoV-2 challenge, reducing by more than 200- fold the peak shedding of SARS-CoV-2 in the nose. MV-014-212 elicited mucosal immunity in the nose and neutralizing antibodies in serum that exhibited cross-neutralization against two virus variants of concern. Intranasally delivered, live attenuated vaccines such as MV-014-212 entail low-cost manufacturing suitable for global deployment. MV-014-212 is currently in phase 1 clinical trials as a single-dose intranasal COVID-19 vaccine.
Key substitutions in the spike protein of SARS-CoV-2 variants can predict resistance to monoclonal antibodies, but other substitutions can modify the effects
Authors: Lusvarghi Sabrina , Wang Wei , Herrup Rachel , Neerukonda Sabari Nath , Vassell Russell , Bentley Lisa , Eakin Ann E. , Erlandson Karl J. , Weiss Carol D. 
Published: July 2021

AbstractMutations in the spike protein of SARS-CoV-2 variants can compromise the effectiveness of therapeutic antibodies. Most clinical-stage therapeutic antibodies target the spike receptor binding domain (RBD), but variants often have multiple mutations in several spike regions. To help predict antibody potency against emerging variants, we evaluated 25 clinical-stage therapeutic antibodies for neutralization activity against 60 pseudoviruses bearing spikes with single or multiple substitutions in several spike domains, including the full set of substitutions in B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.429 (Epsilon), B.1.526 (Iota), A.23.1 and R.1 variants. We found that 14 of 15 single antibodies were vulnerable to at least one RBD substitution, but most combination and polyclonal therapeutic antibodies remained potent. Key substitutions in variants with multiple spike substitutions predicted resistance, but the degree of resistance could be modified in unpredictable ways by other spike substitutions that may reside outside of the RBD. These findings highlight the importance of assessing antibody potency in the context of all substitutions in a variant and show that epistatic interactions in spike can modify virus susceptibility to therapeutic antibodies.ImportanceTherapeutic antibodies are effective in preventing severe disease from SARS-CoV-2 infection (COVID-19), but their effectiveness may be reduced by virus variants with mutations affecting the spike protein. To help predict resistance to therapeutic antibodies in emerging variants, we profiled resistance patterns of 25 antibody products in late stages of clinical development against a large panel of variants that include single and multiple substitutions found in the spike protein. We found that the presence of a key substitution in variants with multiple spike substitutions can predict resistance against a variant, but that other substitutions can affect the degree of resistance in unpredictable ways. These finding highlight complex interactions among substitutions in the spike protein affecting virus neutralization and potentially virus entry into cells.
Pathotyping of Newcastle disease virus: A novel single BsaHI digestion method of detection and differentiation of avirulent strains (lentogenic and mesogenic vaccine strains) from virulent virus
Authors: Desingu Perumal Arumugam , Singh Shambhu Dayal , Dhama Kuldeep , Vinodhkumar Obli Rajendran , Nagarajan K. , Singh Rajendra , Malik Yashpal Singh , Singh Raj Kumar 
Published: July 2021

AbstractWe provide a novel single restriction enzyme (RE) (BsaHI) digestion approach for detecting distinct pathotypes of the Newcastle disease virus (NDV). After scanning 4000 F gene nucleotide sequences in the NCBI database, a single RE (BsaHI) digesting site was discovered in the cleavage site. APMV-I “F gene” Class II specific primer-based reverse transcriptase PCR (RT-PCR) was utilized to amplify a 535 bp fragment, which was then digested with a single RE (BsaHI) for pathotyping avian NDV field isolates and pigeon paramyxovirus-1 isolates. The avirulent (lentogenic and mesogenic strains) produce 189 and 346 bp fragments, respectively, but the result in velogenic strains remains undigested with 535 bp fragments. In addition, 45 field NDV isolates and 8 vaccine strains were used to confirm the approach. The sequence-based analysis also agrees with the data obtained utilizing the single RE (BsaHI) digestion approach. The proposed technique had the potential to distinguish between avirulent and virulent strains in a short space of time, making it valuable in NDV surveillance and monitoring research.
Integrated Genomic Analyses Identify High-Risk Factors and Actionable Targets in T-Cell Acute Lymphoblastic Leukemia
Authors: Zhu Haichuan , Dong Bingjie , Zhang Yingchi , Wang Mei , Rao Jianan , Cui Bowen , Liu Yu , Jiang Qian , Wang Weitao , Yang Lu , Yu Anqi , Li Zongru , Liu Chao , Zhang Leping , Huang Xiaojun , Zhu Xiaofan , Wu Hong 
Published: July 2021

AbstractT cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy often associated with poor outcomes. To identify high-risk factors and potential actionable targets for T-ALL, we perform integrated genomic and transcriptomic analyses on samples from 165 Chinese pediatric and adult T-ALL patients, of whom 85% have outcome information. The genomic mutation landscape of this Chinese cohort is very similar to the Western cohort published previously, except that the rate of NOTCH1 mutations is significant lower in the Chinese T-ALL patients. Among 47 recurrently mutated genes in 7 functional categories, we identify RAS pathway and PTEN mutations as poor survival factors for non-TAL and TAL subtypes, respectively. Mutations in the PI3K pathway are mutually exclusive with mutations in the RAS and NOTCH1 pathways as well as transcription factors. Further analysis demonstrates that approximately 43% of the high-risk patients harbor at least one potential actionable alteration identified in this study, and T-ALLs with RAS pathway mutations are hypersensitive to MEKi in vitro and in vivo. Thus, our integrated genomic analyses not only systematically identify high-risk factors but suggest that these high-risk factors are promising targets for T-ALL therapies.
Intrabody induced cell death by targeting theT. bruceicytoskeletal proteinTbBILBO1
Authors: Broster Reix Christine E. , Ramanantsalama Miharisoa Rijatiana , Primo Carmelo Di , Minder Laëtitia , Bonhivers Mélanie , Dacheux Denis , Robinson Derrick R. 
Published: July 2021

AbstractTrypanosoma bruceibelongs to a genus of protists that cause life-threatening and economically important diseases of human and animal populations in Sub-Saharan Africa. T. bruceicells are covered in surface glycoproteins some of which are used to escape the host immune system. Exo-/endocytotic trafficking of these and other molecules occursviaa single copy organelle called the flagellar pocket (FP). The FP is maintained and enclosed around the flagellum by the flagellar pocket collar (FPC). To date, the most important cytoskeletal component of the FPC is an essential, calcium-binding, polymer-forming protein calledTbBILBO1. In searching for novel immune-tools to study this protein, we raised nanobodies againstTbBILBO1. Nanobodies (Nb) that were selected according to their binding properties toTbBILBO1, were tested as immunofluorescence tools, and expressed as intrabodies (INb). One of them, Nb48, proved to be the most robust nanobody and intrabody. We further demonstrate that inducible, cytoplasmic expression of INb48 was lethal to these parasites, producing abnormal phenotypes resembling those ofTbBILBO1 RNAi knockdown. Our results validate the feasibility of generating functional single-domain antibody derived intrabodies to target trypanosome cytoskeleton proteins.