bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene therapy for Alzheimer’s disease targeting CD33 reduces amyloid beta accumulation and neuroinflammation
Authors: Griciuc Ana , Federico Anthony N , Natasan Jeyashree , Forte Angela M , McGinty Danielle , Nguyen Huong , Volak Adrienn , LeRoy Stanley , Gandhi Sheetal , Lerner Eli P , Hudry Eloise , Tanzi Rudolph E , Maguire Casey A 
Published: August 2020

AbstractNeuroinflammation is a key contributor to the pathology of Alzheimer’s disease (AD). CD33 (Siglec-3) is a transmembrane sialic acid-binding receptor on the surface of microglial cells. CD33 is upregulated on microglial cells from post-mortem AD patient brains, and high levels of CD33 inhibit uptake and clearance of amyloid beta (Aβ) in microglial cell cultures. Furthermore, knockout of CD33 reduces amyloid plaque burden in mouse models of AD. Here, we tested whether a gene therapy strategy to reduce CD33 on microglia in AD could decrease Aβ plaque load. Intracerebroventricular injection of an adeno-associated virus (AAV) vector-based system encoding an artificial microRNA targeting CD33 (miRCD33) into APP/PS1 mice reduced CD33 mRNA and TBS-soluble Aβ40 and Aβ42 levels in brain extracts. Treatment of APP/PS1 mice with miRCD33 vector at an early age (2 months) was more effective at reducing Aβ plaque burden than intervening at later times (8 months). Furthermore, early intervention downregulated several microglial receptor transcripts (e.g. CD11c, CD47 and CD36) and pro-inflammatory activation genes (e.g. Tlr4 and Il1b). Marked reductions in the chemokine Ccl2 and the pro-inflammatory cytokine Tnfα were observed at the protein level in the brain of APP/PS1 mice treated with miRCD33 vector. Overall, our data indicate that CD33 is a viable target for AAV-based knockdown strategies to reduce AD pathology.One Sentence Summary: A gene therapy approach for Alzheimer’s disease using adeno-associated virus vector-based knockdown of CD33 reduced amyloid beta accumulation and neuroinflammation.
Early prediction of mortality risk among patients with severe COVID-19, using machine learning
Authors: Hu Chuanyu , Liu Zhenqiu , Jiang Yanfeng , Shi Oumin , Zhang Xin , Xu Kelin , Suo Chen , Wang Qin , Song Yujing , Yu Kangkang , Mao Xianhua , Wu Xuefu , Wu Mingshan , Shi Tingting , Jiang Wei , Mu Lina , Tully Damien C , Xu Lei , Jin Li , Li Shusheng , Tao Xuejin , Zhang Tiejun , Chen Xingdong 
Published: August 2020

Abstract

Background
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 infection, has been spreading globally. We aimed to develop a clinical model to predict the outcome of patients with severe COVID-19 infection early.

Methods
Demographic, clinical and first laboratory findings after admission of 183 patients with severe COVID-19 infection (115 survivors and 68 non-survivors from the Sino-French New City Branch of Tongji Hospital, Wuhan) were used to develop the predictive models. Machine learning approaches were used to select the features and predict the patients’ outcomes. The area under the receiver operating characteristic curve (AUROC) was applied to compare the models’ performance. A total of 64 with severe COVID-19 infection from the Optical Valley Branch of Tongji Hospital, Wuhan, were used to externally validate the final predictive model.

Results
The baseline characteristics and laboratory tests were significantly different between the survivors and non-survivors. Four variables (age, high-sensitivity C-reactive protein level, lymphocyte count and d-dimer level) were selected by all five models. Given the similar performance among the models, the logistic regression model was selected as the final predictive model because of its simplicity and interpretability. The AUROCs of the external validation sets were 0.881. The sensitivity and specificity were 0.839 and 0.794 for the validation set, when using a probability of death of 50% as the cutoff. Risk score based on the selected variables can be used to assess the mortality risk. The predictive model is available at [https://phenomics.fudan.edu.cn/risk_scores/].

Conclusions
Age, high-sensitivity C-reactive protein level, lymphocyte count and d-dimer level of COVID-19 patients at admission are informative for the patients’ outcomes.
Universal COVID-19 screening of 4040 health care workers in a resource-limited setting: an Egyptian pilot model in a university with 12 public hospitals and medical centers
Authors: Mostafa Aya , Kandil Sahar , El-Sayed Manal H , Girgis Samia , Hafez Hala , Yosef Mostafa , Saber Saly , Ezzelarab Hoda , Ramadan Marwa , Afifi Iman , Hassan Fatmaelzahra , Elsayed Shaimaa , Reda Amira , Fattuh Doaa , Mahmoud Asmaa , Mansour Amany , Sabry Moshira , Habeb Petra , Ebeid Fatma Se , Saleh Ayman , Mansour Ossama , Omar Ashraf , El-Meteini Mahmoud 
Published: August 2020

Abstract

Background
The scale of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among health care workers (HCWs), particularly in resource-limited settings, remains unclear. To address this concern, universal (non-symptom-based) screening of HCWs was piloted to determine the proportion of SARS-CoV-2 infection and the associated epidemiological and clinical risk factors at a large public health care facility in Egypt.

Methods
Baseline voluntary screening of 4040 HCWs took place between 22 April and 14 May 2020 at 12 hospitals and medical centres in Cairo. Epidemiological and clinical data were collected using an online survey. All participants were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR) and rapid IgM and IgG serological tests.

Results
Of the 4040 HCWs screened, 170 [4.2%; 95% confidence interval (CI): 3.6-4.9] tested positive for SARS-CoV-2 by either of the three tests (i.e. infected); 125/170 (73.5%) tested PCR-positive. Most infected HCWs were nurses (97/170, 57.5%). Median age of infected HCWs was 31.5 [interquartile range (IQR): 27.0–41.3] years. Of infected HCWs, 78 (45.9%) reported contact with a suspected case and 47 (27.6%) reported face-to-face contact within 2 m with a confirmed case. The proportion of infection among symptomatic HCWs (n = 54/616) was 8.8% (95% CI: 6.7-11.3); 6/54 (11.1%) had fever ≥38°C and 7/54 (13.0%) reported severe symptoms. Most infected HCWs were asymptomatic (116/170, 68.2%). The proportion of infection among asymptomatic HCWs (n = 116/3424) was 3.4% (95% CI: 2.8-4.0).

Conclusions
The high rate of asymptomatic infections among HCWs reinforces the need for expanding universal regular testing. The infection rate among symptomatic HCWs in this study is comparable with the national rate detected through symptom-based testing. This suggests that infections among HCWs may reflect community rather than nosocomial transmission during the early phase of the COVID-19 epidemic in Egypt.
Sensitivity of ℓ1 minimization to parameter choice
Authors: Berk Aaron , Plan Yaniv , Yilmaz Özgür 
Published: August 2020

Abstract
The use of generalized Lasso is a common technique for recovery of structured high-dimensional signals. There are three common formulations of generalized Lasso; each program has a governing parameter whose optimal value depends on properties of the data. At this optimal value, compressed sensing theory explains why Lasso programs recover structured high-dimensional signals with minimax order-optimal error. Unfortunately in practice, the optimal choice is generally unknown and must be estimated. Thus, we investigate stability of each of the three Lasso programs with respect to its governing parameter. Our goal is to aid the practitioner in answering the following question: given real data, which Lasso program should be used? We take a step towards answering this by analysing the case where the measurement matrix is identity (the so-called proximal denoising setup) and we use $\ell _{1}$ regularization. For each Lasso program, we specify settings in which that program is provably unstable with respect to its governing parameter. We support our analysis with detailed numerical simulations. For example, there are settings where a 0.1% underestimate of a Lasso parameter can increase the error significantly and a 50% underestimate can cause the error to increase by a factor of $10^{9}$.
Molecular Breast Imaging-guided Percutaneous Biopsy of Breast Lesions: A New Frontier on Breast Intervention
Authors: Adrada Beatriz E , Moseley Tanya , Kappadath S Cheenu , Whitman Gary J , Rauch Gaiane M 
Published: August 2020

AbstractMolecular breast imaging (MBI) is an increasingly recognized nuclear medicine imaging modality to detect breast lesions suspicious for malignancy. Recent advances have allowed the development of tissue sampling of MBI-detected lesions using a single-headed camera (breast-specific gamma imaging system) or a dual-headed camera system (MBI system). In this article, we will review current indications of MBI, differences of the two single- and dual-headed camera systems, the appropriate selection of biopsy equipment, billing considerations, and radiation safety. It will also include practical considerations and guidance on how to integrate MBI and MBI-guided biopsy in the current breast imaging workflow.
Net Zero for the International Shipping Sector? An Analysis of the Implementation and Regulatory Challenges of the IMO Strategy on Reduction of GHG Emissions
Authors: Garcia Beatriz , Foerster Anita , Lin Jolene 
Published: August 2020

Abstract
In 2018, the International Maritime Organization (IMO) announced the first sector-wide emission reduction target for international shipping. The roadmap to achieve this goal is the Initial IMO Strategy on Reduction of GHG Emissions from Ships, which proposes implementation measures for the short, medium and long term. This article examines three of these measures: National Action Plans (NAPs), market-based mechanisms (MBMs) and alternative fuels. We argue that NAPs can play a key role in directing national action and facilitating implementation within national jurisdictions. In relation to MBMs, we find that a carbon tax might be more efficient than emission trading. Yet, ultimately, the sector’s decarbonisation can only be truly achieved with zero-carbon fuels. Noting the considerable barriers to the development and use of these fuels, we consider how the private sector is beginning to shift resources to this challenge, spurred by the IMO targets and new understandings of climate-related financial risks and opportunities.
Latent prostate cancer among Japanese males: a bibliometric study of autopsy reports from 1980–2016
Authors: Takeshima Yuta , Suzuki Motofumi , Miyakawa Jimpei , Tsuru Ibuki , Yamada Yuta , Nakamura Masaki , Sato Yusuke , Kawai Taketo , Yamada Daisuke , Morikawa Teppei , Kume Haruki 
Published: August 2020

Abstract
Prostate cancer is one of the most common malignancies, but a substantial portion remains latent throughout the patients’ lifetime. Analysis of temporal change in the latent prostate cancer pool would be beneficial for clinical decision-making, but longitudinal autopsy studies are rare. We conducted a hand-search of the Annual of Pathological Autopsy Cases in Japan from 1980 to 2016 for cases of latent prostate cancer. Of 570 997 males aged 30 or older, latent prostate cancer was detected in 12 562 patients (2.2%). Proportion of detected cases correlated strongly with ‘aging rate’, the percentage of population aged 65 or older (squared Pearson’s correlation coefficient r2 = 0.972, P value &lt;0.0001). Temporal increase in proportion was also seen in each age group as well. This continuous growth reinforces evidence from past Japanese reports on latent prostate cancer. The rapidly rising ageing rate of Japan may forecast further increase in the latent prostate cancer pool moving forward.
Financial Effects of the 2017 Tax Cuts and Jobs Act on Nonindustrial Private Forest Landowners: A Comparative Study for 10 Southern States of the United States
Authors: Baral Srijana , Li Yanshu , Mei Bin 
Published: August 2020

Abstract
Changes in tax codes applicable to timberland investments can affect tax treatment of timber revenues and expenses. The 2017 Tax Cuts and Jobs Act (TCJA) is regarded as the most expansive overhaul of tax codes in the United States since 1986; however, our understanding of its effects on timberland investments for family forest owners has yet to be explored. Using the discounted cash-flow method, we estimated and compared effects of TCJA on land expectation value (LEV) and net tax from managing timberland for two classifications of median-income family forest owners in 10 southern states. Results showed a decrease in LEV and net tax for both material participants and investors, with a greater effect on landowners managing timberland as investments. Thus, owning timberland can become less beneficial under the current law for median-income family forest landowners.
Study Implications: Family forests occupy a large portion of the total forest area in the United States and provide various goods and services to society. Taxes and tax policies are regarded as important issues for these landowners because policies could ultimately influence timberland investment, ownership structure, and management activities. After the 2017 tax reform, landowners became concerned about the effect of the new act on profitability and financial return from timberland investment. Here, we attempt to provide a better understanding of tax effects by estimating change in net benefit of owning and managing timberland under the current law compared with the previous law in 10 southern states. For policymakers, this study can provide insight into the importance of considering unique characteristics of timberland investment during the tax policy design and evaluation process. For landowners, this study can facilitate the timberland investment decisionmaking process and serve as a guide to the effects of the new tax rules on returns.
Military Occupational Disability Risk Surveillance: A Retrospective Cohort Study of Modifiable Risk Factors
Authors: Nelson D Alan , Pflipsen Matthew C , Kurina Lianne M 
Published: August 2020

Abstract

Introduction
Occupational disability among military service members is an important target for preventive screening. The specific aim of this study was to quantify disability risk levels among soldiers with selected risk factors (body mass index extremes, poor or absent physical fitness scores, and tobacco and opioid use) and combinations thereof, suggesting priorities for preventive actions.

Materials and Methods
This was a retrospective cohort study of 607,006 active-duty soldiers who served in the U.S. Army during 2011–2014. Official medical and administrative data were combined to produce a person-month-based panel dataset with identifiers removed. The subjects were observed longitudinally for incident disability (termed medical nonreadiness) during 1,305,618 person-years at risk. We employed Weibull parametric survival regression models to determine the adjusted medical nonreadiness hazard for selected variables. We then computed individual adjusted risk scores and the population proportions affected by risk factors and combinations thereof in postregression analyses. The project was approved by the Stanford University’s Institutional Review Board and underwent secondary review by the Human Research Protections Office of the Defense Health Agency.

Results
During the observed time, 81,571 (13.4%) of subjects were found medically not ready. High or low body mass index, low or missing physical fitness test scores, tobacco use, and the highest levels of opioid use were each associated with increased adjusted hazards of medical nonreadiness. The hazards increased substantially when multiple risk factors were present, albeit while affecting reduced population proportions.

Conclusions
We identified marked disability hazard increases, especially in association with opioid use and high body mass index. These factors, in addition to tobacco use and low physical fitness, are potential early prevention targets for clinicians who screen military service members.
Pulmonary aspergillosis in critically ill patients with Coronavirus Disease 2019 (COVID-19)
Authors: Dupont Damien , Menotti Jean , Turc Jean , Miossec Charline , Wallet Florent , Richard Jean-Christophe , Argaud Laurent , Paulus Sylvie , Wallon Martine , Ader Florence , Persat Florence 
Published: August 2020

Abstract

Occurrence of putative invasive pulmonary aspergillosis was screened in 153 consecutive adult intensive care unit (ICU) patients with respiratory samples addressed for mycological diagnosis during a 6-week period at the emergence of coronavirus disease 2019 (COVID-19) pandemic. Positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) was observed for 106 patients (69.3%). Nineteen of them (17.9%) with positive Aspergillus results were considered as having putative invasive pulmonary aspergillosis. These observations underline the risk of pulmonary aspergillosis in COVID-19 patients, even in patients not previously known to be immunosuppressed, advocating active search for Aspergillus infection and prompt antifungal treatment. Standardized surveillance protocols and updated definitions for ICU putative invasive pulmonary aspergillosis are needed.

Lay Abstract
Adult ICU patients with respiratory samples addressed for mycological diagnosis were screened during the emergence of COVID-19 pandemic. Positive SARS-CoV-2 PCR was observed for 106 patients, nineteen of them (17.9%) having aspergillosis. This underlines the risk of aspergillosis in COVID-19 patients.
A CRISPR-associated factor Csa3a regulates DNA damage repair in Crenarchaeon Sulfolobus islandicus
Authors: Liu Zhenzhen , Sun Mengmeng , Liu Jilin , Liu Tao , Ye Qing , Li Yingjun , Peng Nan 
Published: August 2020

Abstract
CRISPR−Cas system provides acquired immunity against invasive genetic elements in prokaryotes. In both bacteria and archaea, transcriptional factors play important roles in regulation of CRISPR adaptation and interference. In the model Crenarchaeon Sulfolobus islandicus, a CRISPR-associated factor Csa3a triggers CRISPR adaptation and activates CRISPR RNA transcription for the immunity. However, regulation of DNA repair systems for repairing the genomic DNA damages caused by the CRISPR self-immunity is less understood. Here, according to the transcriptome and reporter gene data, we found that deletion of the csa3a gene down-regulated the DNA damage response (DDR) genes, including the ups and ced genes. Furthermore, in vitro analyses demonstrated that Csa3a specifically bound the DDR gene promoters. Microscopic analysis showed that deletion of csa3a significantly inhibited DNA damage-induced cell aggregation. Moreover, the flow cytometry study and survival rate analysis revealed that the csa3a deletion strain was more sensitive to the DNA-damaging reagent. Importantly, CRISPR self-targeting and DNA transfer experiments revealed that Csa3a was involved in regulating Ups- and Ced-mediated repair of CRISPR-damaged host genomic DNA. These results explain the interplay between Csa3a functions in activating CRISPR adaptation and DNA repair systems, and expands our understanding of the lost link between CRISPR self-immunity and genome stability.
Single-molecule fluorescence studies on cotranscriptional G-quadruplex formation coupled with R-loop formation
Authors: Lim Gunhyoung , Hohng Sungchul 
Published: August 2020

Abstract
G-quadruplex (GQ) is formed at various regions of DNA, including telomeres of chromosomes and regulatory regions of oncogenes. Since GQ is important in both gene regulation and genome instability, the biological and medical implications of this abnormal DNA structure have been intensively studied. Its formation mechanisms, however, are not clearly understood yet. We report single-molecule fluorescence experiments to monitor the cotranscriptional GQ formation coupled with R-loop formation using T7 RNA polymerase. The GQ is formed very rarely per single-round transcription. R-loop formation precedes and facilitates GQ formation. Once formed, some GQs are extremely stable, resistant even to RNase H treatment, and accumulate in multiple-round transcription conditions. On the other hand, GQ existing in the non-template strand promotes the R-loop formation in the next rounds of transcription. Our study clearly shows the existence of a positive feedback mechanism of GQ and R-loop formations, which may possibly contribute to gene regulation and genome instability.
A novel siRNA–gemcitabine construct as a potential therapeutic for treatment of pancreatic cancer
Authors: Simonenko Vera , Lu Xiaoyong , Roesch Eric , Mutisya Daniel , Shao Chunbo , Sun Qian , Patterson-Orazem Athéna , McNair Marcus , Shanmuganathan Aranganathan , Lu Patrick , Evans David M 
Published: August 2020

Abstract
The non-nucleoside analog gemcitabine has been the standard of care for treating pancreatic cancer. The drug shows good potency in pancreatic cancer cells in vitro but, due to poor bioavailability, requires administration in large doses by infusion and this systemic exposure results in significant toxicity for the patient. Genes have been identified that, when silenced by siRNA, synergize with gemcitabine treatment and offer a means of reducing the gemcitabine dosage required for efficacy. However, benefiting from the synergism between the two agents requires that the gemcitabine and siRNA penetrate the same cells. To ensure co-delivery, we incorporated gemcitabine covalently within siRNAs against targets synergistic with gemcitabine (CHK1 or RAD17). We demonstrated that specific bases within an siRNA can be replaced with gemcitabine to increase efficacy. The result is a single drug molecule that simultaneously co-delivers gemcitabine and a synergistic siRNA. The siRNA–gemcitabine constructs demonstrate a 5–30-fold improvement in potency compared with gemcitabine alone. Co-delivering a CHK1 siRNA–gemcitabine construct together with a WEE1 siRNA resulted in a 10-fold improvement in IC50 compared with gemcitabine alone. These constructs demonstrate efficacy across a wide array of pancreatic tumor cells and may represent a novel therapeutic approach for treating pancreatic cancer.
Implications of CP invariants for the flavored hybrid neutrino mass matrix
Authors:   HAL QCD Collaboration, Singh Madan 
Published: August 2020

Abstract
We re-examine the weak basis invariants at low energies proposed by C. Jarlskog and Branco et al. in their earlier analyses, after confronting them with the assumptions of two zeros and an equality between arbitrary non-zero elements in the Majorana neutrino mass matrix in the flavored basis. This particular conjecture is found to be experimentally feasible, as shown by S. Dev and D. Raj in their recent work. The present analysis attempts to find the necessary and sufficient condition for CP invariance for each experimentally viable ansatz pertaining to the model, along with some important implications.