bluuebunny/crossref_metadata_2025 huggingface dataset:
Building a Catholic church in 1950s Ireland: architecture, rhetoric and
landscape in Dromore, Co. Cork, 1952–6
Authors: Butler Richard J.
Published: October 2020

This article explores the intellectual culture of Catholic architectural
production in 1950s Ireland through the study of a church-building project
in rural West Cork. It analyses the phenomenon of the Irish ‘church-building
priest’ in terms of their socio-economic background, fundraising abilities,
and position within rural communities – in the context of significant rural
emigration and economic stagnation. It also considers the role that the
Irish countryside played in conditioning clerical understandings of
architectural style and taste, and priests’ political readings of the rural
landscape. Furthermore, it explores the phenomenon of Marianism in church
design and ornamentation around the time of the international ‘Marian Year’
of 1954, and the political meanings of the rhetoric employed by clerics at
church consecration ceremonies. The article concludes with reflections on
social and economic aspects of Irish rural life and religious expression in
a decade primarily understood as one of cultural insularity and conservative
Catholicism.
Controlling contagion? Watercress, regulation and the Hackney typhoid
outbreak of 1903
Authors: Ford Rebecca
Published: October 2020

The part played by the public health movement in controlling epidemics
in urban areas has received considerable attention from historians, as has
the regulation of the milk and meat industries that commenced in the late
nineteenth century. However, comparatively little work has been carried out
on health in a rural context – and the role played by the horticultural
sector in the spread of contagious diseases has barely been covered. Yet, as
this article shows, it was a sector that had the potential to produce potent
contaminants. By examining histories of the production of one horticultural
crop, watercress, it reveals how issues around the provision of a clean
urban water supply and idealised imaginings of the countryside as a pure
space, played a part in exacerbating the extent of outbreaks of typhoid in
the industrial city. It also shows that there was governmental reluctance to
regulate an industry that grew a staple product, even when growers
themselves were keen for guidance.
After-school nutrition education programme improves eating behaviour in economically disadvantaged adolescents
Authors: Shen Pei-Yi , Lo Yuan-Ting C , Chilinda Zizwani Brian , Huang Yi-Chen
Published: October 2020

Objective:

To investigate whether an after-school nutrition education (ASNE) programme can improve the nutrition knowledge and healthy eating behaviour of adolescents from economically disadvantaged families.

Design:

One-group pretest and posttest design. Nutrition knowledge and dietary intake were collected using a questionnaire, and anthropometric measurements were measured before and after the intervention. Nine components of healthy eating behaviour were assessed with reference to the Dietary Guideline of Taiwan. Pretest and posttest differences were analysed using generalised estimating equations.

Setting:

Three after-school programmes in central and southern Taiwan. The ASNE programme comprised three monthly 1-h sessions (20–30-min lecture and 30–40-min interaction).

Participants:

A total of 153 adolescents aged 10–15 years from economically disadvantaged families (seventy-eight elementary students and seventy-five junior high school students).

Results:

Elementary and junior high school students’ nutrition knowledge scores (range 0–6) increased by 0·28 (+ 5·7 %, P = 0·02) and 0·30 points (+ 6·18 %, P = 0·02), respectively, but their fruit intake decreased by 0·36 serving/d (–22·9 %, P = 0·02) and 0·29 serving/d (–18·9 %, P = 0·03), respectively. Junior high school students’ mean snacking frequency and fried food intake dropped to 0·75 d/week (–21·3 %, P = 0·008) and 0·10 serving/d (–28·8 %, P = 0·01), respectively.

Conclusions:

Short-term ASNE programmes can increase nutrition knowledge and reduce snacking frequency and fried food intake despite a decrease in fruit intake among adolescents from economically disadvantaged families.
Molecular characterization of QTL-allele system for drought tolerance at seedling stage and optimal genotype design using multi-locus multi-allele genome-wide association analysis in a half-sib population of soybean (Glycine max (L.) Merr.)
Authors: Khan Mueen Alam , Tong Fei , Wang Wubin , He Jianbo , Zhao Tuanjie , Gai Junyi
Published: October 2020

Characterizing the whole genetic architecture of drought tolerance (DT) is a persistent challenge for the breeders. Here we developed a half-sib population comprising of 404 lines of two recombinant inbred line (RIL) populations with M8206 as the joint parent (M8206 × TongShan and ZhengYang × M8206) and tested for its DT under sand culture. The population was sequenced using restriction-site-associated DNA sequencing filtered with minor allele frequency ≥0.01; 55,936 single nucleotide polymorphisms (SNPs) were obtained and assembled into 6137 SNPLDBs (SNP linkage disequilibrium blocks). The restricted two-stage multi-locus genome-wide association analysis characterized with error and false-positive control identified 40 QTLs with 93 alleles on an average of 34.75% of the phenotypic variance (PV) collectively for relative root length (RRL) and relative shoot length (RSL) that served as potential DT indicators. Among these, eight loci corresponded to previously reported QTLs, whereas 32 loci were therefore novel. The identified QTLs with their corresponding alleles for RRL and RSL were organized into QTL-allele matrices, depicting the comprehensive DT genetic architecture of the three parents/half-sib population. From the matrices, we predicted the possible best/optimal genotype with weighted average value (WAV) 1.553 over two indicators, while for the top 10 single crosses among RILs with 95th percentile WAV was 1.218–1.257, transgressive over the parents (0.693–0.794) yet much less than 1.553. From the detected QTL-allele system, 65 potential candidate genes collectively for both indicators explaining on an average of 24.41% PV were annotated and χ2-tested as a DT candidate gene system involving nine biological processes.
Invented Religion, the Awakened Polis, and Sacred Disestablishment: The Case of Slovenia's “Zombie Church”
Authors: Wadsworth Nancy D. , Črnič Aleš
Published: October 2020

The Trans-Universal Zombie Church of the Blissful Ringing is a religion that emerged in the context of a period of political uprising in Slovenia in 2012–13 and later consolidated into a church that now claims 12,000 members. We use the lens of invented religion and interviews conducted with observers and participants in 2017 to demonstrate ways in which the Zombie Church has been an unusually effective actor in contemporary Slovenian political discourse and, indeed, has broken ground by spotlighting challenges in the young republic's negotiation of the legal and cultural relationships between church, state, and civil society. Part 1 explores the context that led to the mobilization of Zombie as a multivalent symbol for political critique. Part 2 looks at the church's tenets, its success in compelling changes in Slovenia's registration process, and the challenge is its advocates raise to Slovenian church-state structures and practices.
Twenty years on: International humanitarian law and the protection of civilians against the effects of cyber operations during armed conflicts
Authors: Gisel Laurent , Rodenhäuser Tilman , Dörmann Knut
Published: October 2020

The use of cyber operations during armed conflicts and the question of how international humanitarian law (IHL) applies to such operations have developed significantly over the past two decades. In their different roles in the Legal Division of the International Committee of the Red Cross (ICRC), the authors of this article have followed these developments closely and have engaged in governmental and non-governmental expert discussions on the subject. In this article, we analyze pertinent humanitarian, legal and policy questions. We first show that the use of cyber operations during armed conflict has become a reality of armed conflicts and is likely to be more prominent in the future. This development raises a number of concerns in today's increasingly cyber-reliant societies, in which malicious cyber operations risk causing significant disruption and harm to humans. Secondly, we present a brief overview of multilateral discussions on the legal and normative framework regulating cyber operations during armed conflicts, looking in particular at various arguments around the applicability of IHL to cyber operations during armed conflict and the relationship between IHL and the UN Charter. We emphasize that in our view, there is no question that cyber operations during armed conflicts, or cyber warfare, are regulated by IHL – just as is any weapon, means or methods of warfare used by a belligerent in a conflict, whether new or old. Thirdly, we focus the main part of this article on how IHL applies to cyber operations. Analyzing the most recent legal positions of States and experts, we revisit some of the most salient debates of the past decade, such as which cyber operations amount to an “attack” as defined in IHL and whether civilian data enjoys similar protection to “civilian objects”. We also explore the IHL rules applicable to cyber operations other than attacks and the special protection regimes for certain actors and infrastructure, such as medical facilities and humanitarian organizations.
Anthropogenic Decline of African Dust: Insights From the Holocene Records and Beyond
Authors: Yuan Tianle , Yu Hongbin , Chin Mian , Remer Lorraine A. , McGee David , Evan Amato
Published: October 2020

African dust exhibits strong variability on a range of time scales. Here we show that the interhemispheric contrast in Atlantic SST (ICAS) drives African dust variability at decadal to millennial timescales, and the strong anthropogenic increase of the ICAS in the future will decrease African dust loading to a level never seen during the Holocene. We provide a physical framework to understand the relationship between the ICAS and African dust activity: positive ICAS anomalies push the Intertropical Convergence Zone (ITCZ) northward and decrease surface wind speed over African dust source regions, which reduces dust emission and transport. It provides a unified framework for and is consistent with relationships in the literature. We find strong observational and proxy‐record support for the ICAS‐ITCZ‐dust relationship during the past 160 and 17,000 years. Model‐projected anthropogenic increase of the ICAS will reduce African dust by as much as 60%, which has broad consequences.
The Longitudinal Profile of a Prograding River and Its Response to Sea Level Rise
Authors: Gao Weilun , Li Dongxue , Wang Zheng Bing , Nardin William , Shao Dongdong , Sun Tao , Miao Chiyuan , Cui Baoshan
Published: October 2020

River longitudinal profile, a key morphological characteristic of the river channel, is subject to river mouth progradation. Given the increasing influence of human activities and climate change on this critical downstream control, understanding its effects on the evolution of the longitudinal profile is imperative. A general theoretical framework is proposed to quantify the relevant effects, which is tested by numerical experiment and compared with field, numerical and laboratory data from the literature. The results suggest the existence of a critical ratio of accommodation space to sediment supply of approximately 0.5, above which the typical concave upward profile tends to form. Further analyses show that sea level rise tends to increase the concavity of the longitudinal profile of a river with a relatively low equilibrium bed slope and progradation rate.
Groundwater Withdrawal Prediction Using Integrated Multitemporal Remote Sensing Data Sets and Machine Learning
Authors: Majumdar S. , Smith R. , Butler J. J. , Lakshmi V.
Published: October 2020

Key Points

Groundwater withdrawals are not actively monitored in most places of the world at a scale necessary to implement sustainable solutions

Various multitemporal remote sensing data are integrated into a machine learning framework to effectively predict groundwater withdrawals

The results over the High Plains Aquifer, Kansas, USA, show that this approach is applicable to similar regions having sparse in situ data
Defining data-driven subgroups of obsessive–compulsive disorder with different treatment responses based on resting-state functional connectivity
Authors: Kwak Seoyeon , Kim Minah , Kim Taekwan , Kwak Yoobin , Oh Sanghoon , Lho Silvia Kyungjin , Moon Sun-Young , Lee Tae Young , Kwon Jun Soo
Published: October 2020

Characterization of obsessive–compulsive disorder (OCD), like other psychiatric disorders, suffers from heterogeneities in its symptoms and therapeutic responses, and identification of more homogeneous subgroups may help to resolve the heterogeneity. We aimed to identify the OCD subgroups based on resting-state functional connectivity (rsFC) and to explore their differences in treatment responses via a multivariate approach. From the resting-state functional MRI data of 107 medication-free OCD patients and 110 healthy controls (HCs), we selected rsFC features, which discriminated OCD patients from HCs via support vector machine (SVM) analyses. With the selected brain features, we subdivided OCD patients into subgroups using hierarchical clustering analyses. We identified 35 rsFC features that achieved a high sensitivity (82.74%) and specificity (76.29%) in SVM analyses. The OCD patients were subdivided into two subgroups, which did not show significant differences in their demographic and clinical backgrounds. However, one of the OCD subgroups demonstrated more impaired rsFC that was involved either within the default mode network (DMN) or between DMN brain regions and other network regions. This subgroup also showed both lower improvements in symptom severity in the 16-week follow-up visit and lower responder percentage than the other subgroup. Our results highlight that not only abnormalities within the DMN but also aberrant rsFC between the DMN and other networks may contribute to the treatment response and support the importance of these neurobiological alterations in OCD patients. We suggest that abnormalities in these connectivity may play predictive biomarkers of treatment response, and aid to build more optimal treatment strategies.
Decreased mitochondrial electron transport proteins and increased complement mediators in plasma neural-derived exosomes of early psychosis
Authors: Goetzl Edward J. , Srihari Vinod H. , Guloksuz Sinan , Ferrara Maria , Tek Cenk , Heninger George R.
Published: October 2020

Potentially neurotoxic systems involved in traumatic and degenerative diseases of the brain were assessed in acute psychosis. Astrocyte-derived exosomes (ADEs) and neuron-derived exosomes (NDEs) were immunoprecipitated from plasma of ten untreated first-episode psychotics (FPs) and ten matched normal controls (Cs). Neural mitochondrial electron transport and complement proteins were extracted, quantified by ELISAs and normalized with levels of CD81 exosome marker. Levels of subunits 1 and 6 of NADH-ubiquinone oxidoreductase (complex I) and subunit 10 of cytochrome b-c1 oxidase (complex III), but not of subunit 1 of cytochrome C oxidase (complex IV) or superoxide dismutase 1 (SOD1) were significantly lower in ADEs and NDEs of FPs than Cs. This dysregulated pattern of electron transport proteins is associated with increased generation of reactive oxygen species. ADE glial fibrillary acidic protein levels were significantly higher in FPs than Cs, indicating a higher percentage of inflammatory astrocytes in FPs. ADE levels of C3b opsonin were significantly higher and those of C5b-9 attack complex was marginally higher in FPs than Cs. A significantly lower ADE level of the C3 convertase inhibitor CD55 may explain the higher levels of C3 convertase-generated C3b. ADE levels of the neuroprotective protein leukemia inhibitory factor (LIF) were significantly lower in FPs than Cs, whereas levels of IL-6 were no different. Plasma neural exosome levels of electron transport and complement proteins may be useful in predicting FP and guiding therapy. SOD mimetics, C3 convertase inhibitors and LIF receptor agonists also may have therapeutic benefits in FP.
A multiresolution framework to characterize single-cell state landscapes
Authors: Mohammadi Shahin , Davila-Velderrain Jose , Kellis Manolis
Published: October 2020

Dissecting the cellular heterogeneity embedded in single-cell transcriptomic data is challenging. Although many methods and approaches exist, identifying cell states and their underlying topology is still a major challenge. Here, we introduce the concept of multiresolution cell-state decomposition as a practical approach to simultaneously capture both fine- and coarse-grain patterns of variability. We implement this concept in ACTIONet, a comprehensive framework that combines archetypal analysis and manifold learning to provide a ready-to-use analytical approach for multiresolution single-cell state characterization. ACTIONet provides a robust, reproducible, and highly interpretable single-cell analysis platform that couples dominant pattern discovery with a corresponding structural representation of the cell state landscape. Using multiple synthetic and real data sets, we demonstrate ACTIONet’s superior performance relative to existing alternatives. We use ACTIONet to integrate and annotate cells across three human cortex data sets. Through integrative comparative analysis, we define a consensus vocabulary and a consistent set of gene signatures discriminating against the transcriptomic cell types and subtypes of the human prefrontal cortex.
Differential reinforcement encoding along the hippocampal long axis helps resolve the explore–exploit dilemma
Authors: Dombrovski Alexandre Y. , Luna Beatriz , Hallquist Michael N.
Published: October 2020

When making decisions, should one exploit known good options or explore potentially better alternatives? Exploration of spatially unstructured options depends on the neocortex, striatum, and amygdala. In natural environments, however, better options often cluster together, forming structured value distributions. The hippocampus binds reward information into allocentric cognitive maps to support navigation and foraging in such spaces. Here we report that human posterior hippocampus (PH) invigorates exploration while anterior hippocampus (AH) supports the transition to exploitation on a reinforcement learning task with a spatially structured reward function. These dynamics depend on differential reinforcement representations in the PH and AH. Whereas local reward prediction error signals are early and phasic in the PH tail, global value maximum signals are delayed and sustained in the AH body. AH compresses reinforcement information across episodes, updating the location and prominence of the value maximum and displaying goal cell-like ramping activity when navigating toward it.
Two-tier supramolecular encapsulation of small molecules in a protein cage
Authors: Edwardson Thomas G. W. , Tetter Stephan , Hilvert Donald
Published: October 2020

Expanding protein design to include other molecular building blocks has the potential to increase structural complexity and practical utility. Nature often employs hybrid systems, such as clathrin-coated vesicles, lipid droplets, and lipoproteins, which combine biopolymers and lipids to transport a broader range of cargo molecules. To recapitulate the structure and function of such composite compartments, we devised a supramolecular strategy that enables porous protein cages to encapsulate poorly water-soluble small molecule cargo through templated formation of a hydrophobic surfactant-based core. These lipoprotein-like complexes protect their cargo from sequestration by serum proteins and enhance the cellular uptake of fluorescent probes and cytotoxic drugs. This design concept could be applied to other protein cages, surfactant mixtures, and cargo molecules to generate unique hybrid architectures and functional capabilities.
E-cadherin focuses protrusion formation at the front of migrating cells by impeding actin flow
Authors: Grimaldi Cecilia , Schumacher Isabel , Boquet-Pujadas Aleix , Tarbashevich Katsiaryna , Vos Bart Eduard , Bandemer Jan , Schick Jan , Aalto Anne , Olivo-Marin Jean-Christophe , Betz Timo , Raz Erez
Published: October 2020

The migration of many cell types relies on the formation of actomyosin-dependent protrusions called blebs, but the mechanisms responsible for focusing this kind of protrusive activity to the cell front are largely unknown. Here, we employ zebrafish primordial germ cells (PGCs) as a model to study the role of cell-cell adhesion in bleb-driven single-cell migration in vivo. Utilizing a range of genetic, reverse genetic and mathematical tools, we define a previously unknown role for E-cadherin in confining bleb-type protrusions to the leading edge of the cell. We show that E-cadherin-mediated frictional forces impede the backwards flow of actomyosin-rich structures that define the domain where protrusions are preferentially generated. In this way, E-cadherin confines the bleb-forming region to a restricted area at the cell front and reinforces the front-rear axis of migrating cells. Accordingly, when E-cadherin activity is reduced, the bleb-forming area expands, thus compromising the directional persistence of the cells.
The global population of SARS-CoV-2 is composed of six major subtypes
Authors: Morais Ivair José , Polveiro Richard Costa , Souza Gabriel Medeiros , Bortolin Daniel Inserra , Sassaki Flávio Tetsuo , Lima Alison Talis Martins
Published: October 2020

The World Health Organization characterized COVID-19 as a pandemic in March 2020, the second pandemic of the twenty-first century. Expanding virus populations, such as that of SARS-CoV-2, accumulate a number of narrowly shared polymorphisms, imposing a confounding effect on traditional clustering methods. In this context, approaches that reduce the complexity of the sequence space occupied by the SARS-CoV-2 population are necessary for robust clustering. Here, we propose subdividing the global SARS-CoV-2 population into six well-defined subtypes and 10 poorly represented genotypes named tentative subtypes by focusing on the widely shared polymorphisms in nonstructural (nsp3, nsp4, nsp6, nsp12, nsp13 and nsp14) cistrons and structural (spike and nucleocapsid) and accessory (ORF8) genes. The six subtypes and the additional genotypes showed amino acid replacements that might have phenotypic implications. Notably, three mutations (one of them in the Spike protein) were responsible for the geographical segregation of subtypes. We hypothesize that the virus subtypes detected in this study are records of the early stages of SARS-CoV-2 diversification that were randomly sampled to compose the virus populations around the world. The genetic structure determined for the SARS-CoV-2 population provides substantial guidelines for maximizing the effectiveness of trials for testing candidate vaccines or drugs.
Systematic investigation of promoter substitutions resulting from somatic intrachromosomal structural alterations in diverse human cancers
Authors: Alaei-Mahabadi Babak , Elliott Kerryn , Larsson Erik
Published: October 2020

One of the ways in which genes can become activated in tumors is by somatic structural genomic rearrangements leading to promoter swapping events, typically in the context of gene fusions that cause a weak promoter to be substituted for a strong promoter. While identifiable by whole genome sequencing, limited availability of this type of data has prohibited comprehensive study of the phenomenon. Here, we leveraged the fact that copy number alterations (CNAs) arise as a result of structural alterations in DNA, and that they may therefore be informative of gene rearrangements, to pinpoint recurrent promoter swapping at a previously intractable scale. CNA data from nearly 9500 human tumors was combined with transcriptomic sequencing data to identify several cases of recurrent activating intrachromosomal promoter substitution events, either involving proper gene fusions or juxtaposition of strong promoters to gene upstream regions. Our computational screen demonstrates that a combination of CNA and expression data can be useful for identifying novel fusion events with potential driver roles in large cancer cohorts.
A device for surveillance of vascular access sites for bleeding: results from a clinical evaluation trial
Authors: Chionh Chang Yin , Soh Desilyn Yuqing , Tan Chee How , Khaw Jien-Yi , Wong Ying Ching ,   CREMERE Group, Roy Debajyoti Malakar , Koduri Sreekanth , Ng Alvin Kok Heong , Poh Cheng Boon , Ng Chee Yong , Yeon Wenxiang , Foong Shaohui
Published: October 2020

Post-procedural wound haemorrhage is a potentially life-threatening complication. For haemodialysis patients, bleeding is often encountered after vascular access procedures and fatal episodes have been reported. Visual monitoring for bleeding is manpower intensive and bleeding episodes may still be missed between inspections. A device, Blood WArning Technology with Continuous Haemoglobin sensor (BWATCH), was developed to detect bleeding from wounds. This a prospective, observational clinical trial on patients who have had a dialysis catheter inserted or removed. The battery-powered, disc-shaped device (43 mm diameter, 12 mm height) was placed over the dressing for at least six hours. The device detects reflected light with characteristics specific for haemoglobin and an alarm would be triggered if bleeding occurs. There were 250 participants (177 post-insertion, 73 post-removal) and 36 episodes of bleeding occurred. The device alarm was triggered in all instances but there were also 9 false alarms. Specificity was 95.8%, false positive rate was 4.2% and positive predictive value was 80.0%. Sensitivity and negative predictive value were 100% but detection failure may still occur due to improper application or device maintenance. The use of technological aids for monitoring improves patient safety and may reduce demand on manpower.
Fabrication of tri-layered electrospun polycaprolactone mats with improved sustained drug release profile
Authors: Kamath S. Manjunath , Sridhar K. , Jaison D. , Gopinath V. , Ibrahim B. K. Mohamed , Gupta Nilkantha , Sundaram A. , Sivaperumal P. , Padmapriya S. , Patil S. Shantanu
Published: October 2020

Modulation of initial burst and long term release from electrospun fibrous mats can be achieved by sandwiching the drug loaded mats between hydrophobic layers of fibrous polycaprolactone (PCL). Ibuprofen (IBU) loaded PCL fibrous mats (12% PCL-IBU) were sandwiched between fibrous polycaprolactone layers during the process of electrospinning, by varying the polymer concentrations (10% (w/v), 12% (w/v)) and volume of coat (1 ml, 2 ml) in flanking layers. Consequently, 12% PCL-IBU (without sandwich layer) showed burst release of 66.43% on day 1 and cumulative release (%) of 86.08% at the end of 62 days. Whereas, sandwich groups, especially 12% PCLSW-1 & 2 (sandwich layers—1 ml and 2 ml of 12% PCL) showed controlled initial burst and cumulative (%) release compared to 12% PCL-IBU. Moreover, crystallinity (%) and hydrophobicity of the sandwich models imparted control on ibuprofen release from fibrous mats. Further, assay for cytotoxicity and scanning electron microscopic images of cell seeded mats after 5 days showed the mats were not cytotoxic. Nuclear Magnetic Resonance spectroscopic analysis revealed weak interaction between ibuprofen and PCL in nanofibers which favors the release of ibuprofen. These data imply that concentration and volume of coat in flanking layer imparts tighter control on initial burst and long term release of ibuprofen.
Multi-gene signature of microcalcification and risk prediction among Taiwanese breast cancer
Authors: Tsai Hsin-Tien , Huang Ching-Shui , Tu Chao-Chiang , Liu Chih-Yi , Huang Chi-Jung , Ho Yuan-Soon , Tu Shih-Hsin , Tseng Ling-Ming , Huang Chi-Cheng
Published: October 2020

Microcalcification is one of the most common radiological and pathological features of breast ductal carcinoma in situ (DCIS), and to a lesser extent, invasive ductal carcinoma. We evaluated messenger RNA (mRNA) transcriptional profiles associated with ectopic mammary mineralization. A total of 109 breast cancers were assayed with oligonucleotide microarrays. The associations of mRNA abundance with microcalcifications and relevant clinical features were evaluated. Microcalcifications were present in 86 (79%) patients by pathological examination, and 81 (94%) were with coexistent DCIS, while only 13 (57%) of 23 patients without microcalcification, the invasive diseases were accompanied with DCIS (χ2-test, P < 0.001). There were 69 genes with differential mRNA abundance between breast cancers with and without microcalcifications, and 11 were associated with high-grade (comedo) type DCIS. Enriched Gene Ontology categories included glycosaminoglycan and aminoglycan metabolic processes and protein ubiquitination, indicating an active secretory process. The intersection (18 genes) of microcalcificaion-associated and DCIS-associated genes provided the best predictive accuracy of 82% with Bayesian compound covariate predictor. Ten genes were further selected for prognostic index score construction, and five-year relapse free survival was 91% for low-risk and 83% for high-risk group (log-rank test, P = 0.10). Our study suggested that microcalcification is not only the earliest detectable radiological sign for mammography screening but the phenomenon itself may reflect the underling events during mammary carcinogenesis. Future studies to evaluate the prognostic significance of microcalcifications are warranted.
An analytical approach to determine the optimal duration of continuous glucose monitoring data required to reliably estimate time in hypoglycemia
Authors: Camerlingo Nunzio , Vettoretti Martina , Facchinetti Andrea , Sparacino Giovanni , Mader Julia K. , Choudhary Pratik , Del Favero Simone
Published: October 2020

Diabetes is a chronic metabolic disease that causes blood glucose (BG) concentration to make dangerous excursions outside its physiological range. Measuring the fraction of time spent by BG outside this range, and, specifically, the time-below-range (TBR), is a clinically common way to quantify the effectiveness of therapies. TBR is estimated from data recorded by continuous glucose monitoring (CGM) sensors, but the duration of CGM recording guaranteeing a reliable indicator is under debate in the literature. Here we framed the problem as random variable estimation problem and studied the convergence of the estimator, deriving a formula that links the TBR estimation error variance with the CGM recording length. Validation is performed on CGM data of 148 subjects with type-1-diabetes. First, we show the ability of the formula to predict the uncertainty of the TBR estimate in a single patient, using patient-specific parameters; then, we prove its applicability on population data, without the need of parameters individualization. The approach can be straightforwardly extended to other similar metrics, such as time-in-range and time-above-range, widely adopted by clinicians. This strengthens its potential utility in diabetes research, e.g., in the design of those clinical trials where minimal CGM monitoring duration is crucial in cost-effectiveness terms.
Staphylococcus aureus secretes immunomodulatory RNA and DNA via membrane vesicles
Authors: Rodriguez Blanca V. , Kuehn Meta J.
Published: October 2020

Bacterial-derived RNA and DNA can function as ligands for intracellular receptor activation and induce downstream signaling to modulate the host response to bacterial infection. The mechanisms underlying the secretion of immunomodulatory RNA and DNA by pathogens such asStaphylococcus aureusand their delivery to intracellular host cell receptors are not well understood. Recently, extracellular membrane vesicle (MV) production has been proposed as a general secretion mechanism that could facilitate the delivery of functional bacterial nucleic acids into host cells.S. aureusproduce membrane-bound, spherical, nano-sized, MVs packaged with a select array of bioactive macromolecules and they have been shown to play important roles in bacterial virulence and in immune modulation through the transmission of biologic signals to host cells. Here we show thatS. aureussecretes RNA and DNA molecules that are mostly protected from degradation by their association with MVs. Importantly, we demonstrate that MVs can be delivered into cultured macrophage cells and subsequently stimulate a potent IFN-β response in recipient cells via activation of endosomal Toll-like receptors. These findings advance our understanding of the mechanisms by which bacterial nucleic acids traffic extracellularly to trigger the modulation of host immune responses.
Major discrepancy between factual antibiotic resistance and consumption in South of France: analysis of 539,037 bacterial strains
Authors: Diallo Ousmane Oumou , Baron Sophie Alexandra , Dubourg Gregory , Chaudet Hervé , Halfon Philippe , Camiade Sabine , Comte Béatrice , Joubert Stéphanie , François Arnaud , Seyral Philippe , Parisot François , Casalta Jean-Paul , Ruimy Raymond , Maruejouls Christophe , Achiardy Jean-Christophe , Burignat Sophie , Carvajal Joseph , Delaunay Edouard , Meyer Sandra , Levy Pierre-Yves , Roussellier Patricia , Brunet Patrick , Bosi Claude , Stolidi Philippe , Arzouni Jean-Pierre , Gay Gisele , Hance Pierre , Colson Philippe , Raoult Didier , Rolain Jean-Marc
Published: October 2020

The burden of antibiotic resistance is currently estimated by mathematical modeling, without real count of resistance to key antibiotics. Here we report the real rate of resistance to key antibiotics in bacteria isolated from humans during a 5 years period in a large area in southeast in France. We conducted a retrospective study on antibiotic susceptibility of 539,107 clinical strains isolated from hospital and private laboratories in south of France area from January 2014 to January 2019. The resistance rate to key antibiotics as well as the proportion of bacteria classified as Difficult-to-Treat (DTR) were determined and compared with the Mann–Whitney U test, the χ2 test or the Fisher’s exact test. Among 539,037 isolates, we did not observe any significant increase or decrease in resistance to key antibiotics for 5 years, (oxacillin resistance in Staphylococcus aureus, carbapenem resistance in enterobacteria and Pseudomonas aeruginosa and 3rd generation cephalosporin resistance in Escherichia coli and Klebsiella pneumoniae). However, we observed a significant decrease in imipenem resistance for Acinetobacter baumannii from 2014 to 2018 (24.19–12.27%; p = 0.005) and a significant increase of ceftriaxone resistance in Klebsiella pneumoniae (9.9–24.03%; p = 0.001) and Enterobacter cloacae (24.05–42.05%; p = 0.004). Of these 539,037 isolates, 1604 (0.3%) had a DTR phenotype. Over a 5-year period, we did not observe a burden of AR in our region despite a high rate of antibiotic consumption in our country. These results highlight the need for implementation of real-time AR surveillance systems which use factual data.
The vertical stratification of potential bridge vectors of mosquito-borne viruses in a central Amazonian forest bordering Manaus, Brazil
Authors: Hendy Adam , Hernandez-Acosta Eduardo , Valério Danielle , Mendonça Claudia , Costa Edson Rodrigues , Júnior José Tenaçol Andes , Assunção Flamarion Prado , Scarpassa Vera Margarete , Gordo Marcelo , Fé Nelson Ferreira , Buenemann Michaela , de Lacerda Marcus Vinícius Guimarães , Hanley Kathryn A. , Vasilakis Nikos
Published: October 2020

The emergence of Zika virus (ZIKV) in Latin America brought to the fore longstanding concerns that forests bordering urban areas may provide a gateway for arbovirus spillback from humans to wildlife. To bridge urban and sylvatic transmission cycles, mosquitoes must co-occur with both humans and potential wildlife hosts, such as monkeys, in space and time. We deployed BG-Sentinel traps at heights of 0, 5, 10, and 15 m in trees in a rainforest reserve bordering Manaus, Brazil, to characterize the vertical stratification of mosquitoes and their associations with microclimate and to identify potential bridge vectors. Haemagogus janthinomys and Sabethes chloropterus, two known flavivirus vectors, showed significant stratification, occurring most frequently above the ground. Psorophora amazonica, a poorly studied anthropophilic species of unknown vector status, showed no stratification and was the most abundant species at all heights sampled. High temperatures and low humidity are common features of forest edges and microclimate analyses revealed negative associations between minimum relative humidity, which was inversely correlated with maximum temperature, and the occurrence of Haemagogus and Sabethes mosquitoes. In this reserve, human habitations border the forest while tamarin and capuchin monkeys are also common to edge habitats, creating opportunities for the spillback of mosquito-borne viruses.
Mineral soil conditioner requirement and ability to adjust soil acidity
Authors: Yang Xiangdong , Feng Yashuang , Zhang Xiaohong , Sun Mingxue , Qiao Dan , Li Juan , Li Xiaoyan
Published: October 2020

Mineral soil conditioners (MSCs) are used to regulate soil acidity and improve soil quality; they are often made in sintering potassium feldspar, limestone, or dolomite, and are alkaline materials rich in silicon, calcium, potassium, and magnesium. The key point of how to apply them into farmlands is their ability to adjust soil acidity and the MSCs requirement (MSCR). In this study, inductively coupled plasma-optical emission spectroscopy (ICP-OES) analysis and X-ray diffraction (XRD) were firstly used to determine the elemental and phase compositions of the MSCs in order to establish its equivalent relationship for the depletion of soil activity (H+) and its conversion relationship with CaCO3. Secondly, the soil culture method and the improved Shoemaker Mclean Peatt–Double Buffer (SMP–DB) method were compared using a group of 14 typical acid soils in MSCR. It is investigated that the MSCs contained four alkali/alkaline earth–metal elements: Ca, Mg, K, and Na in the bound aluminosilicate form (Ca2MgAlSi2O7, Ca3(SiO3)3, KAlSiO4, and KAlSi2O6); and the depletion of 2.31 mol of H+ required 100 g of MSCs and the amount of Si–Ca–K–Mg MSC needed to deplete the same quantity of H+ was only 0.87 times that of CaCO3. Based on the calculations by using the SMP-DB method and the soil culture method, the MSCR for treating the 14 typical acid soils were in the range of 0.56–8.27 t hm−2 and 0–10.8 t hm−2, respectively. Data from both methods were highly correlated with each other and there was a good linear correlation between them, and the equation: $${{MSC}_{R}}^{{\prime}}=30.29d-0.77$$

MSC

R

′

=
30.29
d
-
0.77

could be used to calculate the MSCs requirement. The recommended MSCR was approximately 4–8, 2–6, and 1–3 t hm−2 when soil pH < 4.50, 4.50 < pH < 5.50, and pH > 5.50, respectively. The experimental and computational methods established in this study could serve as the scientific basis and theoretical guidance for the production and agricultural use of MSCs.
Using chemiluminescence imaging of cells (CLIC) for relative protein quantification
Authors: Fisher Jane , Sørensen Ole E. , Abu-Humaidan Anas H. A.
Published: October 2020

Cell physiology and cellular responses to external stimuli are partly controlled through protein binding, localization, and expression level. Thus, quantification of these processes is pivotal in understanding cellular biology and disease pathophysiology. However, it can be methodologically challenging. Immunofluorescence is a powerful technique, yet quantification by this method can be hampered by auto-fluorescence. Here we describe a simple, sensitive and robust chemiluminescence-based immunoassay (chemiluminescence imaging of cells; CLIC) for relative quantification of proteins. We first employed this method to quantify complement activation in cultured mammalian cells, and to quantify membrane protein expression, shedding, binding and internalization. Moreover, through specific membrane permeabilization we were able to quantify both cytosolic and nuclear proteins, and their translocation. We validated the CLIC quantification method by performing parallel experiments with other quantification methods like ELISA, qPCR, and immunofluorescence microscopy. The workflow of the immunoassay was found to be advantageous in certain instances when compared to these quantification methods. Since the reagents used for CLIC are common to other immunoassays with no need for specialized equipment, and due to the good linearity, dynamic range and signal stability inherent to chemiluminescence, we suggest that this assay is suitable for both small scale and high throughput relative protein quantification studies in whole cells.
Rotational symmetry of photonic bound states in the continuum
Authors: Li Liangsheng , Li Yunzhou , Zhu Yong , Yin Hongcheng
Published: October 2020

The bound states in the continuum (BICs) have been investigated by simulating the optical reflectivity of a tri-layer photonic crystal slab. We found that optical BICs can occur in a class of photonic crystal systems with $$c_{1}^{z}$$

c

1

z

, $$c_{2}^{z}$$

c

2

z

or $$c_{4}^{z}$$

c

4

z

rotational symmetries, which are constructed by three identical photonic crystal slabs. By applying the two mode coupled model, we obtain the reflectivity formula to fit the numerical data and evaluate the lifetime of radiation decay. In vicinity of BIC, the lifetime diverges as a power law form, when approaching the BIC point. The infinity life time of $$c_{1}^{z} {\text{ } - \text{ BIC}}$$

c

1

z

-

BIC

in the tri-layer structure indicate that it is a true BIC. The $$c_{1}^{z} {\text{ } - \text{ BIC}}$$

c

1

z

-

BIC

occurs robustly in tri-layer structures, but the resonance frequency of the BICs is dependent on the permittivity of slab, air-hole size and hole shape.
The water chemistry and microbiome of household wells in Medawachchiya, Sri Lanka, an area with high prevalence of chronic kidney disease of unknown origin (CKDu)
Authors: McDonough Liza K. , Meredith Karina T. , Nikagolla Chandima , Middleton Ryan J. , Tan Jian K. , Ranasinghe Asanga V. , Sierro Frederic , Banati Richard B.
Published: October 2020

Chronic kidney disease (CKD) of unknown etiology (CKDu) mostly affects agricultural communities in Central America, South Asia, Africa, but likely also in North America and Australia. One such area with increased CKDu prevalence is the Medawachchiya District Secretariat Division of the Anuradhapura District in the North Central Province of Sri Lanka. Recent research has focused on the presence of various microbial pathogens in drinking water as potential causal or contributing factors to CKDu, yet no study to date has performed a more comprehensive microbial and water chemistry assessment of household wells used for domestic water supply in areas of high CKDu prevalence. In this study, we describe the chemical composition and total microbial content in 30 domestic household wells in the Medawachchiya District Secretariat Division. While the chemical composition in the tested wells mostly lies within standard drinking water limits, except for high levels of fluoride (F), magnesium (Mg), sodium (Na), chloride (Cl) and calcium (Ca) in some samples, we find a frequent presence of cyanotoxin-producing Microcystis, confirming earlier studies in Sri Lanka. Since the total microbial content of drinking water also directly influences the composition of the human gut microbiome, it can be considered an important determinant of health. Several bacterial phyla were previously reported in the gut microbiome of patients with CKD. Using these bacteria phyla to define operational taxonomic units, we found that these bacteria also occur in the microbiome of the sampled well water. Based on available environmental data, our study demonstrates associations between the abundances of these bacteria with geographical distribution, well water temperature and likely fertilizer use in the local surface water catchment area of the individual household wells. Our results reinforce the recommendation that household wells with stagnant or infrequently used water should be purged prior to use for drinking water, bathing and irrigation. The latter is suggested because of the reported potential accumulation of bacterial toxins by agricultural crops. The observation that bacteria previously found in chronic kidney disease patients are also present in household wells requires a more detailed systematic study of both the human gut and drinking water microbiomes in CKDu patients, in relation to disease prevalence and progression.
Protective effect of vaccinating infants with a 5 µg recombinant yeast-derived hepatitis B vaccine and the need for a booster dose in China
Authors: Miao Ning , Zheng Hui , Sun Xiaojin , Zhang Guomin , Wang Fuzhen
Published: October 2020

In 2002, China integrated hepatitis B vaccine (HepB) into its Expanded Program on Immunization (EPI) using HepB vaccine containing 5 µg of antigen. Although not recommended nationally, there was a common clinical practice in China of screening children for anti-HBs antibody level and giving a booster dose to HBV surface antigen (HBsAg)-negative children with non-protective anti-HBs antibody levels. We report an evaluation of the protective effectiveness of the 5 µg HepB vaccine and the serological response to the booster dose. We used data from a 2014 hepatitis B serological survey to determine HBsAg positivity and anti-HBs antibody levels among children who received and did not receive a booster dose. We determined HepB coverage from the Children Immunization Information Management System (CIIMS). We obtained and analyzed reports of acute Hepatitis B (AHB) during 2008–2014 obtained from the National Notifiable Disease Reporting System (NNDRS). The HBsAg-positive rate among children who had not received a booster dose was 0.41%, and did not increase with age (i.e., time since infant immunization). The anti-HBs positivity rate among the 6% of children who received a booster dose (88.41%) was higher than among those who had not received a booster (60.85%); anti-HBs antibody levels declined with age regardless of booster dose status. There was no statistically significant difference in HBsAg positivity between children who received a booster dose and those who did not. The AHB incidence among children born between 2002 and 2007 did not increase with age. Use of routine 5 µg HepB vaccine was not associated with an increase in AHB or of HBsAg positivity by time since vaccination, providing supportive evidence that individuals vaccinated with the 5 µg HepB vaccine do not need a booster dose. Although a booster dose was associated with increases in anti-HBs antibody levels, our study provided no evidence to support the need for this clinical practice. We should continue to strengthen serological monitoring of children, especially for those born to HBsAg positive mothers.