bluuebunny/crossref_metadata_2025 huggingface dataset:
Traditional Horticulture Practices Increase the Production of Selected Withanolides in Withania Somnifera (L.) Dunal—A RP-UFLC Analysis
Authors: Ankad Gireesh M , Pai Sandeep R , Hiremath Jagadishchandra , Hegde Harsha V
Published: August 2020

The study evaluates the effect of two traditional horticulture treatments mentioned in Vrikshayurveda, a text from ancient India on the science of plant life, namely Kunapa jala (KJ) and Pancha gavya (PG) on the production of Withaferin A (WFA), withanolide A (WIA) and Withanolide B (WIB) in Withania somnifera (L) Dunal. Leaves and roots of W. somnifera were collected from different treated groups viz. control, KJ, PG, farmyard manure (FYM) and inorganic fertilizer (NPK). Reverse phase ultra-flow liquid chromatography (RP-UFLC) method was developed, validated for simultaneous detection of WFA, WIA and WIB. Statistical analysis of data was performed by ANOVA and tested for significance by the Dunnett multiple comparison test and data were expressed as mean ± standard deviation (SD). Results revealed, leaves possessed highest WFA content and roots possessed highest content of WIA and WIB. PG treated leaves were observed highest WFA (18.29 mg/g) and roots were observed highest WIA (19.63 mg/g) and WIB (1.36 mg/g). Conclusively, RP-UFLC method for simultaneous detection of withanolides has been developed and validated to evaluate the effect of traditional horticulture treatments. It is concluded that the enhanced production of withanolides can be achieved by the application of PG when compared to NPK application.
Towards an epistemology for conjunctural inter-urban comparison
Authors: Leitner Helga , Sheppard Eric
Published: August 2020

We propose an epistemology for conjunctural inter-urban comparison, stressing the dialectical relationship between the general and the particular. We spatialise conjunctural analysis, avoiding methodological territorialism by extending the explanatory framework outwards in space to incorporate inter-territorial connections and supra-territorial scalar relations. We then provide three guiding principles for conjunctural comparison: an open starting point, a three-dimensional socio-spatial ontology and the general/particular dialectic. Illustrating this with comparative fieldwork on urban land transformations in Jakarta and Bangalore, we stress-test received theories and develop Inter-scalar Chains of Rentiership: this mid-range concept clarifies shared tendencies across the cities, particularities differentiating them and their inter-relations.
Pyrrhonian Scepticism in Thomas Elyot'sDefence of Good Women(1540)
Authors: Gligorijevic Kosta
Published: August 2020

This article discusses the first known mention of Pyrrhonian Scepticism in the English language, which occurs in Thomas Elyot’s 1540 Defence of Good Women. The article inquires into the sources of Elyot’s knowledge of Pyrrhonism and into his motivations for mentioning Pyrrhonists in a text on the social and political status of women. I conclude that, on the balance of evidence, the most likely source of Elyot’s ideas on Pyrrhonism is Galen’s De Temperamentis. Furthermore, I argue that the rejection of a straw man version of Pyrrhonism serves as a tool of authorial positioning for Elyot, and in particular as a means of reassuring his reader that the Defence is not intended ironically. Elyot chooses Pyrrhonism as a philosophical position representing bad faith arguments, and he likely does so because of the hostile treatment of Pyrrhonism in Galen’s works, and especially in De Temperamentis.
Coronavirus disease 2019 (COVID-19) in the heart transplant population: a single-centre experience
Authors: Caraffa Raphael , Bagozzi Lorenzo , Fiocco Alessandro , Bifulco Olimpia , Nadali Matteo , Ponzoni Matteo , Carrozzini Massimiliano , Toscano Giuseppe , Fraiese Angela Pompea , Metra Marco , Lombardi Carlo Maria , Serafini Francesco , Ribola Angela , Jorgji Vjola , Bottio Tomaso , Gerosa Gino
Published: August 2020

OBJECTIVES

Few anecdotal cases have been reported in the literature regarding heart transplant recipients and infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report our experience with 6 patients hospitalized in Northern Italy during the outbreak.

METHODS

Of the 396 living heart transplant recipients from 1985 to 2020 included in the study, 6 patients developed the novel 2019 coronavirus disease. Risk factors, last follow-up characteristics, onset presentation, in-hospital course of disease and blood examinations data were collected for these patients.

RESULTS

All patients were symptomatic and had positive results from a nasopharyngeal swab test for SARS-CoV-2. Of the 6 patients, 5 were hospitalized and 1 remained self-quarantined at home. Two patients died and 3 were discharged home. Two patients were admittted to the intensive care unit . Immunosuppressive therapy was modified with a median reduction comprising doses that were 50% cyclosporine and 50% mycophenolate. All patients received a medium-dose of corticosteroids as a bolus medication in addition to their therapy. All hospitalized patients received hydroxychloroquine; 2 patients received ritonavir/lopinavir. Broad-spectrum antibiotics for prophylaxis were administered to all. One patient had an ischaemic stroke and died of sepsis.

CONCLUSIONS

In the absence of any strong evidence regarding the treatment of heart transplant recipients infected with SARS-CoV-2, we faced a new challenge in managing viral infection in an immunosuppressed population. Because immunomodulation interaction with the infection seems to be crucial for developing severe forms of the disease, we managed to reduce immunosuppressive therapy by adding medium doses of corticosteroids. Despite the limited number of affected patients, this report suggests that special considerations should be given to treating coronavirus disease in the heart transplant recipient population.
Organizing talk in group speaking tests: learning from high-scoring students
Authors: Stephenson Michael , Hall Graham
Published: August 2020

This article investigates how group speaking test candidates manage group talk during assessed, time-limited tasks. Drawing on recorded and transcribed data, it explores how higher-scoring learners manage spoken assessment tasks through their talk, moving conversations on or slowing them down in order to perform and complete the tasks’ requirements in a timely way. These data are contrasted with the ways in which lower-scoring test candidates attempt to organize and manage assessed group talk. While the data and findings from this particular study can be used to teach students about, and prepare them for, multi-person discussions and, more specifically, task-oriented and time-limited group speaking tests, we also suggest that our awareness-raising investigatory approach, if brought into the classroom, offers learners (and teachers) a way of uncovering some of what actually occurs during talk, illuminating the ‘invisible rules’ that guide how participants engage in and manage interaction.
Bacterial and fungal diversity in the lorandite (TlAsS2) mine ‘Allchar' in the Republic of North Macedonia
Authors: Taleski Vaso , Dimkić Ivica , Boev Blazo , Boev Ivan , Živković Sanja , Stanković Slaviša
Published: August 2020

The Allchar mineral mine is one of the oldest arsenic–antimony mines in the Republic of North Macedonia. The mine is a well-known reservoir of the worldwide purest source of the thallium-bearing mineral, lorandite (TlAsS2). The current study evaluated the bacterial and fungal diversity of three As- and Tl-contaminated sites in Allchar mineral mine. We used a combination of high-throughput sequencing and bioinformatic analyses. Trace metal content was detected using inductively coupled plasma optical emission spectrometry. Our analysis showed the presence of 25 elements and confirmed a high concentration of As and Tl. Alpha diversity indices suggested a high diversity and evenness of bacterial and fungal communities. Bacterial phyla that dominated the environment were Bacteroidetes, Acidobacteria, Planctomycetes, Actinobacteria and Verrucomicrobia. Looking at the genus level, we found the following groups of bacteria: Chryseolinea, Opitutus, Flavobacterium, Pseudomonas, Terrimonas, Sphingomonas and Reyranella. For the fungi genera, we report Tetracladium sp., Coprinellus micaceus, Coprinus sp. from Ascomycota and Basidiomycota phyla in all sites. We also observed a high abundance of the fungal species Pilidium sp., Dendroclathra lignicola, Rosellinia desmazieri, Hypomyces rosellus and Coprinellus disseminatus. This study is the first to identify specific As- and Tl-tolerant fungal (Pilidium sp., Cladophialophora sp., Neobulgaria sp. and Mycena acicula) and bacterial (Trichococcus, Devosia, Litorilinea and Gimesia) genera from Allchar mine, suggesting bioremediation and industrial potential.
Structurally complex carbohydrates maintain diversity in gut-derived microbial consortia under high dilution pressure
Authors: Yao Tianming , Chen Ming-Hsu , Lindemann Stephen R
Published: August 2020

Dietary fibers are major substrates for maintaining and shaping gut microbiota, but the structural specificity of these fibers for the diversity, structure and function of gut microbiota are poorly understood. Here, we employed an in vitro sequential batch fecal culture approach to address two ecological questions: (i) whether the chemical complexity of a carbohydrate influences its ability to maintain microbial diversity against high dilution pressure (ii) whether substrate structuring or obligate microbe-microbe metabolic interactions (e.g. exchange of amino acids or vitamins) exert more influence on maintained diversity. Sorghum arabinoxylan (SAX, a complex polysaccharide), inulin (a low-complexity oligosaccharide) and their corresponding monosaccharide controls were selected as model carbohydrates. Our results demonstrate that complex carbohydrates stably sustain diverse microbial consortia. Furthermore, other metabolic interactions were less influential in structuring microbial consortia consuming SAX than inulin. Finally, very similar final consortia were enriched on SAX from the same individual's fecal microbiota one month later, suggesting that polysaccharide structure is more influential than stochastic alterations in microbiome composition in governing the outcomes of sequential batch cultivation experiments. These data suggest that carbohydrate structural complexity affords independent niches that structure fermenting microbial consortia, whereas other metabolic interactions govern the composition of communities fermenting simpler carbohydrates.
Mucoidy, a general mechanism for maintaining lytic phage in populations of bacteria
Authors: Chaudhry Waqas , Lee Esther , Worthy Andrew , Weiss Zoe , Grabowicz Marcin , Vega Nicole , Levin Bruce
Published: August 2020

We present evidence that phage resistance resulting from overproduction of exopolysaccharides, mucoidy, provides a general answer to the longstanding question of how lytic viruses are maintained in populations dominated by bacteria upon which they cannot replicate. In serial transfer culture, populations of mucoid Escherichia coli MG1655 that are resistant to lytic phages with different receptors, and thereby requiring independent mutations for surface resistance, are capable of maintaining these phages with little effect on their total density. Based on the results of our analysis of a mathematical model, we postulate that the maintenance of phage in populations dominated by mucoid cells can be attributed primarily to high rates of transition from the resistant mucoid states to susceptible non-mucoid states. Our tests with both population dynamic and single cell experiments as well as genomic analysis are consistent with this hypothesis. We discuss reasons for the generalized resistance of these mucoid E. coli, and the genetic and molecular mechanisms responsible for the high rate of transition from mucoid to sensitive states responsible for the maintenance of lytic phage in mucoid populations of E. coli.
The Effects of Autocratic Characteristics on Public Opinion toward Democracy Promotion Policies: A Conjoint Analysis
Authors: Escribà-Folch Abel , Muradova Lala H , Rodon Toni
Published: August 2020

Does the level of public support for democracy promotion policies vary with the characteristics of potential autocratic targets? We conduct an experimental study with a conjoint design on a sample of 1,464 US citizens that manipulates several core characteristics of potential autocratic targets. We then compare citizens’ preferences with the cross-national evidence testing the determinants of democracy promotion success. We find that respondents support the use of coercive measures (military action and sanctions) precisely in contexts where, according to comparative research, these instruments are unlikely to foster democratization: oil-rich, exclusionary, personalistic regimes with no elections, and with no ties to the United States. Conversely, the characteristics driving public support for the use of democracy aid are more consistent with those favoring effectiveness: autocratic regimes with multi-party elections and with links to the United States. These findings have important policy implications by contributing to understand the micro-foundations of target selection.
Microhomologies Are Associated with Tandem Duplications and Structural Variation in Plant Mitochondrial Genomes
Authors: Xia Hanhan , Zhao Wei , Shi Yong , Wang Xiao-Ru , Wang Baosheng
Published: August 2020

Short tandem repeats (STRs) contribute to structural variation in plant mitochondrial genomes, but the mechanisms underlying their formation and expansion are unclear. In this study, we detected high polymorphism in the nad7-1 region of the Pinus tabuliformis mitogenome caused by the rapid accumulation of STRs and rearrangements over a few million years ago. The STRs in nad7-1 have a 7-bp microhomology (TAG7) flanking the repeat array. We then scanned the mitogenomes of 136 seed plants to understand the role of microhomology in the formation of STR and mitogenome evolution. A total of 13,170 STRs were identified, and almost half of them were associated with microhomologies. A substantial amount (1,197) of microhomologies was long enough to mediate structural variation, and the length of microhomology is positively correlated with the length of tandem repeat unit. These results suggest that microhomology may be involved in the formation of tandem repeat via microhomology-mediated pathway, and the formation of longer duplicates required greater length of microhomology. We examined the abundance of these 1,197 microhomologies, and found 75% of them were enriched in the plant mitogenomes. Further analyses of the 400 prevalent microhomologies revealed that 175 of them showed differential enrichment between angiosperms and gymnosperms and 186 differed between angiosperms and conifers, indicating lineage-specific usage and expansion of microhomologies. Our study sheds light on the sources of structural variation in plant mitochondrial genomes and highlights the importance of microhomology in mitochondrial genome evolution.
Expression Evolution of Ancestral XY Gametologs across All Major Groups of Placental Mammals
Authors: Martínez-Pacheco Mónica , Tenorio Mariela , Almonte Laura , Fajardo Vicente , Godínez Alan , Fernández Diego , Cornejo-Páramo Paola , Díaz-Barba Karina , Halbert Jean , Liechti Angelica , Székely Tamas , Urrutia Araxi O , Cortez Diego
Published: August 2020

Placental mammals present 180 million-year-old Y chromosomes that have retained a handful of dosage-sensitive genes. However, the expression evolution of Y-linked genes across placental groups has remained largely unexplored. Here, we expanded the number of Y gametolog sequences by analyzing ten additional species from previously unexplored groups. We detected seven remarkably conserved genes across 25 placental species with known Y repertoires. We then used RNA-seq data from 17 placental mammals to unveil the expression evolution of XY gametologs. We found that Y gametologs followed, on average, a 3-fold expression loss and that X gametologs also experienced some expression reduction, particularly in primates. Y gametologs gained testis specificity through an accelerated expression decay in somatic tissues. Moreover, despite the substantial expression decay of Y genes, the combined expression of XY gametologs in males is higher than that of both X gametologs in females. Finally, our work describes several features of the Y chromosome in the last common mammalian ancestor.
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

Neuroinflammation 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

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

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

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

Molecular 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

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

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 <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

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

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

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

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

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

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

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.
A systematic review and meta-analysis of the association between periodontitis and oral high-risk human papillomavirus infection
Authors: Ali Anna , Lassi Zohra S , Kapellas Kostas , Jamieson Lisa , Rumbold Alice R
Published: August 2020

Background

The incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is increasing globally. Common oral conditions such as periodontitis may contribute. We undertook a meta-analysis to quantify the association between periodontitis, oral HPV and OPSCCs.

Methods

Multiple electronic databases were searched until 12 February 2020. Studies conducted in males and/or females aged ≥ 18 years that examined periodontitis, periodontal procedures, oral HPV infection, and where possible, oral cancers, were eligible. Meta-analyses were conducted and the GRADE approach was used to examine the quality of evidence.

Results

Of 2709 studies identified, 13 met the eligibility criteria. Five studies could be included in the meta-analyses. There was no significant increase in the odds of high-risk oral HPV infection among individuals with confirmed periodontitis (odds ratio 4.71, 95% confidence interval 0.57–38.97). Individuals with periodontitis had a 3.65 times higher odds of having any type of oral HPV infection compared with those without periodontitis (95% confidence interval 1.67–8.01). The overall body of evidence was rated as low to very-low certainty.

Conclusion

Meta-analysis confirms there is a positive association between periodontitis and oral HPV infection, although the overall quality of this evidence is low. Evidence for an association between periodontitis and high-risk oral HPV infection is inconclusive.
Impulsive Consumption and Financial Well-Being: Evidence from an Increase in the Availability of Alcohol
Authors: Ben-David Itzhak , Bos Marieke
Published: August 2020

The increased availability of alcohol may harm individuals who have present-focused preferences and consume more than initially planned. Using a nationwide experiment in Sweden, we study the credit behavior of low-income households around the expansion of liquor stores’ operating hours on Saturdays. Consistent with store closures serving as commitment devices, the policy led to higher credit demand, more default, increased dependence on welfare, and higher crime on Saturdays. The effects are concentrated on the young population due to higher alcohol consumption combined with tight liquidity constraints. The policy’s impact on indebtedness is estimated at 4.5 times the expenditure on alcohol.
The MIR137 VNTR rs58335419 Is Associated With Cognitive Impairment in Schizophrenia and Altered Cortical Morphology
Authors: Mahmoudi Ebrahim , Atkins Joshua R , Quidé Yann , Reay William R , Cairns Heath M , Fitzsimmons Chantel , Carr Vaughan J , Green Melissa J , Cairns Murray J
Published: August 2020

Genome-wide association studies (GWAS) of schizophrenia have strongly implicated a risk locus in close proximity to the gene for miR-137. While there are candidate single-nucleotide polymorphisms (SNPs) with functional implications for the microRNA’s expression encompassed by the common haplotype tagged by rs1625579, there are likely to be others, such as the variable number tandem repeat (VNTR) variant rs58335419, that have no proxy on the SNP genotyping platforms used in GWAS to date. Using whole-genome sequencing data from schizophrenia patients (n = 299) and healthy controls (n = 131), we observed that the MIR137 4-repeats VNTR (VNTR4) variant was enriched in a cognitive deficit subtype of schizophrenia and associated with altered brain morphology, including thicker left inferior temporal gyrus and deeper right postcentral sulcus. These findings suggest that the MIR137 VNTR4 may impact neuroanatomical development that may, in turn, influence the expression of more severe cognitive symptoms in patients with schizophrenia.
Do Unremitted Psychotic Symptoms Have an Effect on the Brain? A 2-Year Follow-up Imaging Study in First-Episode Psychosis
Authors: Lepage Martin , Makowski Carolina , Bodnar Michael , Chakravarty M Mallar , Joober Ridha , Malla Ashok K
Published: August 2020

Background

To examine whether the duration of unremitted psychotic symptoms after the onset of a first episode of psychosis (FEP) is associated with cortical thickness and hippocampal volume, as well as structural covariance of these measures.

Method

Longitudinal MRI scans were obtained for 80 FEP patients shortly after entry to FEP clinic (baseline), and then 12 months and 24 months later. The proportion of time patients experienced unremitted positive symptoms for 2 interscan intervals (baseline to 12 mo, 12 mo to 24 mo) was calculated. Changes in cortical thickness and hippocampal volumes were calculated for each interscan interval and associated with duration of unremitted psychotic symptoms. Significant regions were then used in seed-based structural covariance analyses to examine the effect of unremitted psychotic symptoms on brain structural organization. Importantly, analyses controlled for antipsychotic medication.

Results

Cortical thinning within the left medial/orbitofrontal prefrontal cortex and superior temporal gyrus were significantly associated with the duration of unremitted psychotic symptoms during the first interscan interval (ie, baseline to 12 mo). Further, changes in cortical thickness within the left medial/orbitofrontal cortex positively covaried with changes in thickness in the left dorsal and ventrolateral prefrontal cortex during this period. No associations were observed during the second interscan interval, nor with hippocampal volumes.

Conclusions

These results demonstrate that cortical thickness change can be observed shortly after an FEP, and these changes are proportionally related to the percentage of time spent with unremitted psychotic symptoms. Altered structural covariance in the prefrontal cortex suggests that unremitted psychotic symptoms may underlie reorganization in higher-order cortical regions.
Role for Anti-Cytokine Therapies in Severe Coronavirus Disease 2019
Authors: Buckley Leo F. , Wohlford George F. , Ting Clara , Alahmed Abdullah , Van Tassell Benjamin W. , Abbate Antonio , Devlin John W. , Libby Peter
Published: August 2020

Objectives:

The causative agent for coronavirus disease 2019, severe acute respiratory syndrome coronavirus 2, appears exceptional in its virulence and immunopathology. In some patients, the resulting hyperinflammation resembles a cytokine release syndrome. Our knowledge of the immunopathogenesis of coronavirus disease 2019 is evolving and anti-cytokine therapies are under active investigation. This narrative review summarizes existing knowledge of the immune response to coronavirus infection and highlights the current and potential future roles of therapeutic strategies to combat the hyperinflammatory response of patients with coronavirus disease 2019.

Data Sources:

Relevant and up-to-date literature, media reports, and author experiences were included from Medline, national newspapers, and public clinical trial databases.

Study Selection:

The authors selected studies for inclusion by consensus.

Data Extraction:

The authors reviewed each study and selected approrpriate data for inclusion through consensus.

Data Synthesis:

Hyperinflammation, reminiscent of cytokine release syndromes such as macrophage activation syndrome and hemophagocytic lymphohistiocytosis, appears to drive outcomes among adults with severe coronavirus disease 2019. Cytokines, particularly interleukin-1 and interleukin-6, appear to contribute importantly to such systemic hyperinflammation. Ongoing clinical trials will determine the efficacy and safety of anti-cytokine therapies in coronavirus disease 2019. In the interim, anti-cytokine therapies may provide a treatment option for adults with severe coronavirus disease 2019 unresponsive to standard critical care management, including ventilation.

Conclusions:

This review provides an overview of the current understanding of the immunopathogenesis of coronavirus disease 2019 in adults and proposes treatment considerations for anti-cytokine therapy use in adults with severe disease.
It's not that mesh, is it? What providers should know about the transvaginal mesh controversy
Authors: Hudson Patricia L. , DeAndrade Samantha P. , Weinstein Milena M.
Published: August 2020

The U.S. Food and Drug Administration recent ban on surgical mesh intended for the transvaginal repair of pelvic organ prolapse has called into question the safety of surgical mesh implants in general. As the media firestorm around vaginal mesh kits has continued to grow, important details about the specific type of mesh involved have been lost in the public discourse surrounding the controversy. This has left healthcare providers across the nation in the difficult position of addressing patient anxieties about the use of mesh in gynecologic surgery. This review seeks to educate women's health providers on the historical background and various uses of the different types of mesh in gynecologic surgery.