bluuebunny/crossref_metadata_2025 huggingface dataset:
Ruminal acidosis, bacterial changes, and lipopolysaccharides
Authors: Monteiro Hugo F , Faciola Antonio P
Published: August 2020

Acute and subacute ruminal acidosis (SARA) are common nutritional problems in both beef and dairy cattle. Therefore, the objective of this review is to describe how ruminal Gram-negative bacteria could contribute to the pathogenesis of ruminal acidoses, by releasing lipopolysaccharides (LPS; a component of their cell wall) in the ruminal fluid. When cattle consume excessive amounts of highly fermentable carbohydrates without prior adaptation, normal fermentation become disrupted. The fermentation of these carbohydrates quickly decreases ruminal pH due to the accumulation of short-chain fatty acids and lactate in the rumen. As a consequence, ruminal epithelium may be damaged and tissue function could be impaired, leading to a possible translocation of pathogenic substances from the rumen into the bloodstream. Such changes in fermentation are followed by an increase in Gram-positive bacteria while Gram-negative bacteria decrease. The lyses of Gram-negative bacteria during ruminal acidosis increase LPS concentration in the ruminal fluid. Because LPS is a highly proinflammatory endotoxin in the circulatory system, past studies have raised concerns regarding ruminal LPS contribution to the pathogenesis of ruminal acidosis. Although animals that undergo these disorders do not always have an immune response, recent studies showed that different Gram-negative bacteria have different LPS composition and toxicity, which may explain the differences in immune response. Given the diversity of Gram-negative bacteria in the rumen, evaluating the changes in the bacterial community during ruminal acidosis could be used as a way to identify which Gram-negative bacteria are associated with LPS release in the rumen. By identifying and targeting ruminal bacteria with possible pathogenic LPS, nutritional strategies could be created to overcome, or at least minimize, ruminal acidosis.
RNA-recognition motifs and glycine and arginine-rich region cooperatively regulate the nucleolar localization of nucleolin
Authors: Okuwaki Mitsuru , Saotome-Nakamura Ai , Yoshimura Masashi , Saito Shoko , Hirawake-Mogi Hiroko , Sekiya Takeshi , Nagata Kyosuke
Published: August 2020

Nucleolin (NCL) is a nucleolar protein i.e. involved in the regulation of the nucleolar structure and functions, and consists of three distinct regions: the N-terminal region; the middle region, which contains four RNA-recognition motifs (RRMs); and the C-terminal glycine- and arginine-rich (GAR) region. The primary function of the RRMs and GAR is thought to be specific RNA binding. However, it is not well understood how these RNA-binding regions of NCL separately or cooperatively regulate its nucleolar localization and functions. To address this issue, we constructed mutant proteins carrying point mutations at the four RRMs individually or deletion of the C-terminal GAR region. We found that the GAR deletion and the mutations in the fourth RRM (RRM4) decreased the nucleolar localization of NCL. Biochemical analyses showed that NCL interacted directly with ribosomal RNAs (rRNAs) and G-rich oligonucleotides, and that this interaction was decreased by mutations at RRM1 and RRM4 and GAR deletion. Although GAR deletion decreased the rRNA-binding activity of NCL, the mutant was efficiently coprecipitated with rRNAs and nucleolar proteins from cell extracts. These contradictory results suggest that NCL stably localizes to the nucleoli via the interactions with rRNAs and nucleolar proteins via GAR, RRM1 and RRM4.
Acetabular cartilage repair: state of the art in surgical treatment
Authors: Bagheri Kian , Sierra Frank , Jamali Amir A
Published: August 2020

Hip preservation has emerged as a developing surgical subspecialty with a variety of tools to address hip joint pain and dysfunction. Cartilage tears and delamination are caused by injury to the hip and can ultimately progress to osteoarthritis. It has been established that the acetabulum is particularly at risk of cartilage injury secondary to trauma, hip dysplasia and hip impingement. In spite of the high frequency of acetabular cartilage lesions based on our experience and the literature, there is no consensus as to the optimal treatment of these lesions. This review article highlights the challenges in treating cartilage injuries of the acetabulum with a particular emphasis on published studies and technical considerations in performing these procedures.
Towards real-time DNA biometrics using GPU-accelerated processing
Authors: Reja Mario , Pungila Ciprian , Negru Viorel
Published: August 2020

Decoding the human genome in the past decades has brought into focus a computationally intensive operation through DNA profiling. The typical search space for these kinds of problems is extremely large and requires specialized hardware and algorithms to perform the necessary sequence analysis. In this paper, we propose an innovative and scalable approach to exact multi-pattern matching of nucleotide sequences by harnessing the massively parallel computing power found in commodity graphical processing units. Our approach places careful consideration on preprocessing of DNA datasets and runtime performance, while exploiting the full capabilities of the heterogeneous platform it runs on. Finally, we evaluate our models against real-world DNA sequences.
Attitudes Toward Collusion in Chile
Authors: Aydin Umut
Published: August 2020

In the last two decades, competition agencies around the world have increasingly directed their attention to enforcement against cartels. With the encouragement of the antitrust authorities of the United States, and the Organization of Economic Cooperation and Development, various countries have introduced leniency programs, and sanctions for individuals found guilty of colluding. Critics are concerned, however, that these measures are not backed by broad public support, which could jeopardize their enforcement. This paper explores public attitudes toward cartels in Chile, an emerging economy that introduced a leniency program in 2009 and criminal sanctions in 2016, by presenting the results of a public opinion survey conducted in this country in August–September 2019. The results of the survey show high awareness of cartels and the harm they cause, and high public disapproval of cartel conduct among the Chilean respondents. In particular, up to 70 percent of the respondents support prison sentences against individuals found guilty of colluding. Such strong public support for anti-cartel measures could be considered positive from the perspective of enforcement. The results also emphasize the importance of continued competition advocacy directed at the society to explain and gain public support for the anti-cartel agenda.
Chronic pancreatitis with ductal stones in the pancreatic head treated by surgery: a case report
Authors: Meyer Alberto , Koszka Andreas Johann Molnar , Abreu Phillipe , Ferreira Raphaella , Fantauzzi Marcelo Callado , Segatelli Vanderlei , David Andre Ibrahim
Published: August 2020

Pancreatic duct stones are direct sequelae of chronic pancreatitis (CP) and can occur in ∼50% of patients. Selection of the appropriate treatment method for pancreatic duct stones depends on location, size and number of stones. We present a patient with upper abdominal pain and weight loss for the previous 3 months. Diagnostic workup detected a chronic inflammation of the pancreas with stone in the main pancreatic duct and a nodular lesion in the head of the pancreas. Endoscopic retrograde cholangiopancreatography was performed without success. Given the rise in incidence and prevalence of CP, the potential complications and high mortality rate, it is imperative that physicians understand the risk factors, disease process and management of this disease. Pancreaticoduodenectomy in patients with CP is a feasible option for the treatment of focal cystic lesions to the head of the pancreas associated to pancreatic stone in selected cases.
A 3D simulation of a neutrino-driven supernova explosion aided by convection and magnetic fields
Authors: Müller Bernhard , Varma Vishnu
Published: August 2020

We study the impact of a small-scale dynamo in core-collapse supernovae using a 3D neutrino magnetohydrodynamics (MHD) simulation of a 15 M⊙ progenitor. The weak seed field is amplified exponentially in the gain region once neutrino-driven convection develops, and remains dominated by small-scale structures. About $250\, \mathrm{ms}$ after bounce, the field energy in the gain region reaches ${\sim } 50{{\ \rm per\ cent}}$ of kinetic equipartition. This supports the development of a neutrino-driven explosion with modest global anisotropy, which does not occur in a corresponding model without magnetic fields. Our results suggest that magnetic fields may play a beneficial subsidiary role in neutrino-driven supernovae even without rapid progenitor rotation. Further investigation into the nature of MHD turbulence in the supernova core is required.
Benchmark study comparing liftover tools for genome conversion of epigenome sequencing data
Authors: Luu Phuc-Loi , Ong Phuc-Thinh , Dinh Thanh-Phuoc , Clark Susan J
Published: August 2020

As reference genome assemblies are updated there is a need to convert epigenome sequence data from older genome assemblies to newer versions, to facilitate data integration and visualization on the same coordinate system. Conversion can be done by re-alignment of the original sequence data to the new assembly or by converting the coordinates of the data between assemblies using a mapping file, an approach referred to as ‘liftover’. Compared to re-alignment approaches, liftover is a more rapid and cost-effective solution. Here, we benchmark six liftover tools commonly used for conversion between genome assemblies by coordinates, including UCSC liftOver, rtracklayer::liftOver, CrossMap, NCBI Remap, flo and segment_liftover to determine how they performed for whole genome bisulphite sequencing (WGBS) and ChIP-seq data. Our results show high correlation between the six tools for conversion of 43 WGBS paired samples. For the chromatin sequencing data we found from interval conversion of 366 ChIP-Seq datasets, segment_liftover generates more reliable results than USCS liftOver. However, we found some regions do not always remain the same after liftover. To further increase the accuracy of liftover and avoid misleading results, we developed a three-step guideline that removes aberrant regions to ensure more robust genome conversion between reference assemblies.
Executive summary from American Radium Society’s appropriate use criteria on neurocognition after stereotactic radiosurgery for multiple brain metastases
Authors: Milano Michael T , Chiang Veronica L S , Soltys Scott G , Wang Tony J C , Lo Simon S , Brackett Alexandria , Nagpal Seema , Chao Samuel , Garg Amit K , Jabbari Siavash , Halasz Lia M , Gephart Melanie Hayden , Knisely Jonathan P S , Sahgal Arjun , Chang Eric L
Published: August 2020

Background

The American Radium Society (ARS) Appropriate Use Criteria brain malignancies panel systematically reviewed (PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses]) published literature on neurocognitive outcomes after stereotactic radiosurgery (SRS) for patients with multiple brain metastases (BM) to generate consensus guidelines.

Methods

The panel developed 4 key questions (KQs) to guide systematic review. From 11 614 original articles, 12 were selected. The panel developed model cases addressing KQs and potentially controversial scenarios not addressed in the systematic review (which might inform future ARS projects). Based upon quality of evidence, the panel confidentially voted on treatment options using a 9-point scale of appropriateness.

Results

The panel agreed that SRS alone is usually appropriate for those with good performance status and 2–10 asymptomatic BM, and usually not appropriate for >20 BM. For 11–15 and 16–20 BM there was (between 2 case variants) agreement that SRS alone may be appropriate or disagreement on the appropriateness of SRS alone. There was no scenario (among 6 case variants) in which conventional whole-brain radiotherapy (WBRT) was considered usually appropriate by most panelists. There were several areas of disagreement, including: hippocampal sparing WBRT for 2–4 asymptomatic BM; WBRT for resected BM amenable to SRS; fractionated versus single-fraction SRS for resected BM, larger targets, and/or brainstem metastases; optimal treatment (WBRT, hippocampal sparing WBRT, SRS alone to all or select lesions) for patients with progressive extracranial disease, poor performance status, and no systemic options.

Conclusions

For patients with 2–10 BM, SRS alone is an appropriate treatment option for well-selected patients with good performance status. Future study is needed for those scenarios in which there was disagreement among panelists.
Boundary Management and Communication Technologies
Authors: Cecchinato Marta E. , Cox Anna L.
Published: August 2020

We live in a world of communication overload, where there is a wide range of platforms and devices to choose from, each providing massive content, offering different affordances, and fighting for our attention. Mobile technologies have contributed to expectations of anywhere anytime connectedness, making it hard for individuals to switch off. As a result, it can be hard to feel truly disconnected from work. A lack of control over work-home boundary cross-overs and interruptions can reduce post-work recovery, reducing productivity and increasing stress. Technology is not inherently good or bad, but rather, the way it is adopted and used can positively or negatively color one’s experience. As such, in this critical review we take a social constructionist approach to emphasize how communication technologies are challenging, as well as supporting, work-home boundary management. In doing so, we bring together work from occupational psychology (boundary theory) and human-computer interaction (computer-mediated communication and cross-device interaction). Understanding how these aspects interact and influence each other is important in order to support individuals appropriately, inform policies and guidelines, and ensure both social and digital interactions are designed carefully.
The Greening of Industrial Hubs
Authors: Mathews John A.
Published: August 2020

After the success of East Asian industrialization efforts in the late twentieth century, the twenty-first century has witnessed the turn of industrializing giants, led by China and India, to claim the fruits of advanced manufacturing industries. At the scale of transformation engaged in by these giants, the traditional fossil-fuelled pathway involving oil, gas, and coal is simply not feasible—for reasons to do with energy and resource insecurity and catastrophic urban pollution as much as for concerns over global warming and climate change. The key to success in their endeavours lies not just at the macro level of national industrial sectors, or the micro level of firms, but at the meso level of suprafirm structures and dynamics, involving clusters, industrial hubs, and EPZs. These hubs or clusters provide the optimal setting for greening initiatives, as the industrial parks are turned into eco-industrial parks based on circular economy principles.
Global Value Chains, Industrial Hubs, and Economic Development in the Twenty-first Century
Authors: Gereffi Gary , Wu Xinyi
Published: August 2020

This chapter uses the global value chain (GVC) framework to analyse the shifting strategies of key lead firms and first-tier suppliers in the athletic footwear and electronics industries. Growing cost pressures for labour and raw materials, as well as the potential political disruption from the escalating ‘trade war’ between the United States and China and the accelerating technological disruption sparked by the digital economy on both the demand side (e.g. e-commerce) and the supply side (e.g. automation) of GVCs, are encouraging brand leaders and major suppliers in both GVCs (such as Adidas and Nike in footwear, and Apple and Foxconn in electronics) to pursue automation in select factories in their supply chains. However, the industrial hubs where athletic footwear and electronics production is concentrated remain overwhelmingly labour-intensive, both in China and elsewhere in Asia (such as Vietnam and Indonesia) where big suppliers are moving to diversify their options.
Calling for a united action to defeat COVID-19
Authors: Overby Madison , Pu Qinqin , Wei Xiawei , Wu Min
Published: August 2020

The widespread and lingering pandemic of COVID-19 is partly due to disjointed international countermeasures and policies enforced by different countries. We have been witnessing disparity in policies and measures in different countries and regions: some are in much better control than others. To effectively deal with this and future devastating pandemics, we as human beings must work together to coordinate a concerted, cooperative international policy to reduce or possibly avoid unnecessary health crises, and life and economic losses.
Engineering Escherichia coli towards de novo production of gatekeeper (2S)-flavanones: naringenin, pinocembrin, eriodictyol and homoeriodictyol
Authors: Dunstan Mark S , Robinson Christopher J , Jervis Adrian J , Yan Cunyu , Carbonell Pablo , Hollywood Katherine A , Currin Andrew , Swainston Neil , Feuvre Rosalind Le , Micklefield Jason , Faulon Jean-Loup , Breitling Rainer , Turner Nicholas , Takano Eriko , Scrutton Nigel S
Published: August 2020

Natural plant-based flavonoids have drawn significant attention as dietary supplements due to their potential health benefits, including anti-cancer, anti-oxidant and anti-asthmatic activities. Naringenin, pinocembrin, eriodictyol and homoeriodictyol are classified as (2S)-flavanones, an important sub-group of naturally occurring flavonoids, with wide-reaching applications in human health and nutrition. These four compounds occupy a central position as branch point intermediates towards a broad spectrum of naturally occurring flavonoids. Here, we report the development of Escherichia coli production chassis for each of these key gatekeeper flavonoids. Selection of key enzymes, genetic construct design and the optimization of process conditions resulted in the highest reported titers for naringenin (484 mg/l), improved production of pinocembrin (198 mg/l) and eriodictyol (55 mg/l from caffeic acid), and provided the first example of in vivo production of homoeriodictyol directly from glycerol (17 mg/l). This work provides a springboard for future production of diverse downstream natural and non-natural flavonoid targets.
Lipoarabinomannan Antigen Assay (TB-LAM) for Diagnosing Pulmonary Tuberculosis in Children with Severe Acute Malnutrition in Mozambique
Authors: Osório Dulce-Vasco , Munyangaju Isabelle , Muhiwa Argentina , Nacarapa Edy , Nhangave Amancio-Vicente , Ramos Jose-Manuel
Published: August 2020

Background

Tuberculosis (TB) and malnutrition are important causes of morbidity and mortality in children in the developing world.

Aims

To assess the prevalence of pulmonary TB in severely malnourished children and evaluate TB detection using the urine lipoarabinomannan antigen assay (TB-LAM).

Methods

A retrospective analysis was conducted in all pediatric inpatients with severe acute malnutrition at a rural health center in Mozambique, from February to August 2018. All children underwent a physical examination and chest X-ray, and their nasopharyngeal aspirates and stool specimens were studied for mycobacterial culture and subjected to the Xpert MTB/RIF assay. TB-LAM tests were performed on urine.

Results

Of 45 included cases, 17 (37.8%) were clinically diagnosed as pulmonary TB. None of these were detected by the Xpert MTB test; 4 (8.9%) nasopharyngeal aspirates were TB-culture positive. Seventeen patients (37.8%)—all clinically diagnosed with TB—tested positive on the TB-LAM, while 23 (51.1%) were negative. In 5 (11.1%), the urine LAM was not done.

Conclusion

Although our sample size was small, TB was diagnosed and treated in more than a third of included children. The urine TB-LAM test showed a perfect correlation with clinical diagnosis of childhood TB.

LAY SUMMARY

Severe acute malnutrition makes children more vulnerable to tuberculosis (TB) infections, but it is difficult to detect TB in children because they cannot always cough up phlegm, which is used in diagnostic processes. This study aimed to find out how many severely malnourished children had TB in Gaza, Mozambique, and to test the accuracy of a less-used diagnostic test: the lipoarabinomannan assay (TB-LAM). Of the 45 severely malnourished children who were admitted to our hospital, 17 were diagnosed with TB by their doctor. The TB-LAM corroborated the clinical diagnosis in all cases, while the other tests (Xpert MTB/RIF assay) and cultures failed to detect most of them. Overall, more than a third of severely malnourished children had TB, and the TB-LAM test—a simple, point-of-care method—was a highly accurate way to diagnose them. While larger studies are needed to confirm these results, our findings suggest that the TB-LAM could vastly improve TB diagnosis in malnourished children.
Neonatal and Maternal Composite Adverse Outcomes Among Low-Risk Nulliparous Women Compared With Multiparous Women at 39–41 Weeks of Gestation
Authors: Chauhan Suneet P. , Rice Madeline Murguia , Grobman William A. , Bailit Jennifer , Reddy Uma M. , Wapner Ronald J. , Varner Michael W. , Thorp John M. , Caritis Steve N. , Prasad Mona , Tita Alan T. N. , Saade George R. , Sorokin Yoram , Rouse Dwight J. , Tolosa Jorge E. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network
Published: August 2020

OBJECTIVE:

To estimate whether the frequency of adverse maternal and neonatal outcomes differs between low-risk nulliparous and multiparous women at 39–41 weeks of gestation.

METHODS:

This is a secondary analysis of an observational obstetrics cohort of maternal–neonatal dyads at 25 hospitals. Low-risk women with nonanomalous singletons who delivered between 39 0/7 and 41 6/7 weeks of gestation were included. The composite neonatal adverse outcome included 5-minute Apgar score less than five, ventilator support or cardiopulmonary resuscitation, seizure, hypoxic ischemic encephalopathy, sepsis, bronchopulmonary dysplasia, persistent pulmonary hypertension, necrotizing enterocolitis, birth injury or perinatal death. The composite maternal adverse outcome included infection, third- or fourth-degree perineal laceration, thromboembolism, transfusion of blood products, or maternal death. Small for gestational age (SGA), large for gestational age (LGA), and shoulder dystocia requiring maneuvers were also evaluated. Multivariable regression was used to estimate adjusted relative risks (aRRs) and adjusted odds ratios (aORs) with 95% CIs.

RESULTS:

Of the 115,502 women in the overall cohort, 39,870 (34.5%) met eligibility criteria for this analysis; 18,245 (45.8%) were nulliparous. The risk of the composite neonatal adverse outcome (1.5% vs 1.0%, aRR 1.80, 95% CI 1.48–2.19), composite maternal adverse outcome (15.1% vs 3.3%, aRR 5.04, 95% CI 4.62–5.49), and SGA (8.9% vs 5.8%, aOR 1.45, 95% CI 1.33–1.57) was significantly higher in nulliparous than multiparous patients. The risk of LGA (aOR 0.65, 95% CI 0.60–0.71) and shoulder dystocia with maneuvers (aRR 0.68, 95% CI 0.60–0.77) was significantly lower in nulliparous rather than multiparous patients.

CONCLUSION:

The risk of composite adverse outcomes and SGA among low-risk nulliparous women at 39–41 weeks of gestation is significantly higher than among multiparous counterparts. However, nulliparous women had a lower risk of shoulder dystocia with maneuvers and LGA.
Per- and polyfluoroalkyl substances in drinking water and birthweight in the US
Authors: Zhu Yachen , Bartell Scott M.
Published: August 2020

Background:

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in the serum of the general US population, and were detected in public water systems serving approximately 16.5 million US residents during 2013–2015. Low birthweight was associated with PFAS exposures in previous studies.

Methods:

Birthweights for singleton births during 2013–2015 were obtained from CDC WONDER, multiply stratified by county, maternal age, race, education, smoking status, and parity. PFAS water concentrations were obtained from EPA UCMR3 database and aggregated by county. Multiple regression weighted by inverse variance was used to produce effect estimates equivalent to those that would be obtained from individual-level data on birthweight and confounders.

Results:

Adjusting for stratification demographic confounders (maternal age, race, education, smoking status, and parity), we found an average change in birthweight of 0.9 g (95% confidence interval [CI] = −0.5, 2.2), −1.3 g (−1.6, −0.9), −3.8 g (−4.9, −2.7), and −3.8 g (−4.3, −3.3) per ng/L increase in the population-weighted average perfluorooctanoic acid, perfluorooctane sulfonate, perfluoroheptanoic acid, and perfluorohexane sulfonic acid in public water supplies by county, respectively. We found an average change in birthweight of −1.0 g (95% CI = −1.2, −0.8) per ng/L increase in the sum of perfluorooctanoic acid, perfluorooctane sulfonate, perfluoroheptanoic acid, and perfluorohexane sulfonic acid concentrations in public water supplies.

Conclusions:

The direction and magnitude of association between PFAS and birthweight varied by PFAS chemical in this study. Conclusions are tempered by inherent limitations of the 2 public-use datasets, and by the sensitivity of our results to alternative methods such as mutual adjustment for co-exposures.
Diurnal Temperature Variation and Using Fever to Screen for Infectious Diseases
Authors: Miller Aaron C. , Koeneman Scott , Polgreen Philip M.
Published: August 2020

Fevers have been used as marker of disease state for hundreds of years and are frequently used to screen for infectious diseases during infectious disease outbreaks. However, body temperature and fevers have been shown to vary over the course of a day and across individuals by age, sex and other characteristics. The objective of this paper is to describe the individual variation in diurnal temperature patterns during episodes of febrile activity using a database of millions of recorded temperatures across the United States. We then model the probability of recording a fever during a single reading at given time for individuals who are experiencing a febrile episode. We find a wide variation in body temperatures over the course of a day and across individual characteristics. Similarly, the likelihood of recording a fever may vary widely by the time of day when the reading is taken and by an individual’s age or sex. These results suggest diurnal temperature variation and demographics should be considered when using body temperature to screen for disease, especially for diseases that are contagious.
Testing for SARS-CoV-2 in care home staff and residents in English care homes: A service evaluation
Authors: Smith Emma , Aldus Clare F , Brainard Julii , Dunham Sharon , Hunter Paul R , Steel Nicholas , Everden Paul
Published: August 2020

Background

COVID-19 has especially affected care home residents.

Aim

To evaluate a nurse-led Enhanced Care Home Team (ECHT) enhanced SARS-CoV-2 testing strategy.

Design and setting

Service evaluation in care homes in Norfolk UK.

Method

Residents and staff received nose and throat swab tests (7 April to 29 June 2020). Resident test results were linked with symptoms on days 0-14 after test and mortality to 13 July 2020.

Results

Residents (n=518) in 44 homes and staff (n=340) in 10 care homes were tested. SARS-CoV-2 positivity was identified in 103 residents in 14 homes and 49 staff in seven homes. Of 103 SARS-CoV-2+ residents, just 38 had typical symptom(s) at time of test (new cough and/or fever). Amongst 54 residents who were completely asymptomatic when tested, 12 (22%) developed symptoms within 14 days. Compared to SARS-CoV-2 negative residents, SARS-CoV-2+ residents were more likely to exhibit typical symptoms (new cough (n=26, p=0.001); fever (n=24, p=<0.001)) or as ‘generally unwell’ (n=18, p=0.001). Of 38 resident deaths, 21 (55%) were initially attributed to SARS-CoV-2, all of whom tested SARS-CoV-2+. One death not initially attributed to SARS-CoV-2 also tested positive.

Conclusion

Testing identified asymptomatic and pre-symptomatic SARS-CoV-2+ residents and staff. Being ‘generally unwell’ was common amongst symptomatic residents and may indicate SARS-CoV-2 infection in older people in the absence of more ‘typical’ symptoms. Where a resident appears generally unwell SARS-CoV-2-infection should be suspected. Protocols for testing involved integrated health and social care teams.
Novel Diffuse White Matter Abnormality Biomarker at Term-Equivalent Age Enhances Prediction of Long-term Motor Development in Children Born Very Preterm
Authors: Parikh Nehal A. , Harpster Karen , He Lili , Illapani Venkata Sita Priyanka , Khalid Fatima Chughtai , Klebanoff Mark A. , O’Shea T. Michael , Altaye Mekibib
Published: August 2020

Our objective was to evaluate the independent prognostic value of a novel MRI biomarker – objectively diagnosed diffuse white matter abnormality volume (DWMA; diffuse excessive high signal intensity) – for prediction of motor outcomes in very preterm infants. We prospectively enrolled a geographically-based cohort of very preterm infants without severe brain injury and born before 32 weeks gestational age. Structural brain MRI was obtained at term-equivalent age and DWMA volume was objectively quantified using a published validated algorithm. These results were compared with visually classified DWMA. We used multivariable linear regression to assess the value of DWMA volume, independent of known predictors, to predict motor development as assessed using the Bayley Scales of Infant & Toddler Development, Third Edition at 3 years of age. The mean (SD) gestational age of the cohort was 28.3 (2.4) weeks. In multivariable analyses, controlling for gestational age, sex, and abnormality on structural MRI,DWMA volume was an independent prognostic biomarker of Bayley Motor scores (β= –12.59 [95% CI: –18.70, –6.48] R2=0.41). Conversely, visually classified DWMA was not predictive of motor development. In conclusion, objectively quantified DWMA is an independent prognostic biomarker of long-term motor development in very preterm infants and warrants further study.
ANMerge: A comprehensive and accessible Alzheimer’s disease patient-level dataset
Authors: Birkenbihl Colin , Westwood Sarah , Shi Liu , Nevado-Holgado Alejo , Westman Eric , Lovestone Simon , Hofmann-Apitius Martin
Published: August 2020

Background

Accessible datasets are of fundamental importance to the advancement of Alzheimer’s disease (AD) research. The AddNeuroMed consortium conducted a longitudinal observational cohort study with the aim to discover AD biomarkers. During this study, a broad selection of data modalities was measured including clinical assessments, magnetic resonance imaging, genotyping, transcriptomic profiling and blood plasma proteomics. Some of the collected data were shared with third-party researchers. However, this data was incomplete, erroneous and lacking in interoperability.

Methods

We systematically addressed several limitations of the originally shared data and provide additional unreleased data to enhance the patient-level dataset.

Results

In this work, we publish and describe ANMerge, a new version of the AddNeuroMed dataset. ANMerge includes multimodal data from 1702 study participants and is accessible to the research community via a centralized portal.

Conclusions

ANMerge is an information rich patient-level data resource that can serve as a discovery and validation cohort for data-driven AD research, such as for example machine learning and artificial intelligence approaches.

ANMerge can be downloaded here: https://doi.org/10.7303/syn22252881
Inhomogeneous mixing and asynchronic transmission between local outbreaks account for the spread of COVID-19 epidemics
Authors: Mendoza Carlos I.
Published: August 2020

The ongoing epidemic of COVID-19 originated in China has reinforced the need to develop epidemiological models capable of describing the progression of the disease to be of use in the formulation of mitigation policies. Here, this problem is addressed using a metapopulation approach to show that the delay in the transmission of the spread between different subsets of the total population, can be incorporated into a SIR framework through a time-dependent transmission rate. Thus, the reproduction number decreases with time despite the population dynamics remains uniform and the depletion of susceptible individuals is small. The obtained results are consistent with the early subexponential growth observed in the cumulated number of confirmed cases even in the absence of containment measures. We validate our model by describing the evolution of the COVID-19 using real data from different countries with an emphasis in the case of Mexico and show that it describes correctly also the long-time dynamics of the spread. The proposed model yet simple is successful at describing the onset and progression of the outbreak and considerably improves accuracy of predictions over traditional compartmental models. The insights given here may probe be useful to forecast the extent of the public health risks of epidemics and thus improving public policy-making aimed at reducing such risks.
SWITCHES: Searchable Web Interface for Topologies of CHEmical Switches
Authors: HarshaRani G.V. , Moza S. , Ramakrishnan N. , Bhalla U.S.
Published: August 2020

Bistable biochemical switches are key motifs in cellular state decisions and long-term storage of cellular ‘memory’. There are a few known biological switches that have been well characterized, however these examples are insufficient for systematic surveys of properties of these important systems. Here we present a resource of all possible bistable biochemical reaction networks with up to 6 reactions between 3 molecules, and 3 reactions between 4 molecules. Over 35,000 reaction topologies were constructed by identifying unique combinations of reactions between a fixed number of molecules. Then, these topologies were populated with rates within a biologically realistic range. The Searchable Web Interface for Topologies of CHEmical Switches (SWITCHES,https://switches.ncbs.res.in) provides a bistability and parameter analysis of over 7 million models from this systematic survey of chemical reaction space. This database will be useful for theoreticians interested in analyzing stability in chemical systems and also experimentalists for creating robust synthetic biological switches.

Availability and Implementation

Freely available on the web athttps://switches.ncbs.res.in. Website implemented in PHP, MariaDB, Graphviz, and Apache, with all major browsers supported.

Supplementary Information

Not applicable.
Concerted evolution reveals co-adapted amino acid substitutions in Na+K+-ATPase of frogs that prey on toxic toads
Authors: Mohammadi Shabnam , Yang Lu , Harpak Arbel , Herrera-Álvarez Santiago , Rodríguez-Ordoñez María del Pilar , Peng Julie , Zhang Karen , Storz Jay F. , Dobler Susanne , Crawford Andrew J. , Andolfatto Peter
Published: August 2020

Gene duplication is an important source of evolutionary innovation, but the adaptive division-of-labor between duplicates can be opposed by ongoing gene conversion between them. Here we document a tandem duplication of Na+,K+-ATPase subunit α1 (ATP1A1) shared by frogs in the genusLeptodactylus, a group of species that feeds on toxic toads. One ATP1A1 paralog evolved resistance to toad toxins while the other paralog retained ancestral susceptibility. We show that the twoLeptodactylusparalogs are distinguished by 12 amino acid substitutions that were maintained by strong selection that counteracted the homogenizing effect of gene conversion. Protein-engineering experiments show that two major-effect substitutions confer toxin resistance, whereas the 10 additional substitutions mitigate deleterious pleiotropic effects on enzyme function. Our results highlight how trans-specific, neofunctionalized gene duplicates can provide unique insights into interactions between adaptive substitutions and the genetic backgrounds on which they arise.

One Sentence Summary

Selection counteracts gene conversion to maintain an adaptive division-of-labor between tandemly duplicated genes.
Emotion suppression failures are associated with local increases in sleep-like activity
Authors: Avvenuti Giulia , Bertelloni Davide , Lettieri Giada , Ricciardi Emiliano , Cecchetti Luca , Pietrini Pietro , Bernardi Giulio
Published: August 2020

Emotion self-regulation relies both on cognitive and behavioral strategies implemented to modulate the subjective experience and/or the behavioral expression of a given emotion. While it is known that a network encompassing fronto-cingulate and parietal brain areas is engaged during successful emotion regulation, the functional mechanisms underlying failures in emotion suppression are still unclear. In order to investigate this issue, we analyzed video and high-density EEG recordings of nineteen healthy adult subjects during an emotion suppression (ES) and a free expression (FE) task performed on two consecutive days. Changes in facial expression during ES, but not FE, were preceded by local increases in sleep-like activity (1-4Hz) in in brain areas responsible for emotional suppression, including bilateral anterior insula and anterior cingulate cortex, and in right middle/inferior frontal gyrus (p<0.05, corrected). Moreover, shorter sleep duration the night prior to the ES experiment correlated with the number of behavioral errors (p=0.01) and tended to be associated with higher frontal sleep-like activity during emotion suppression failures (p=0.05). These results indicate that local sleep-like activity may represent the cause of emotion suppression failures in humans, and may offer a functional explanation for previous observations linking lack of sleep, changes in frontal activity and emotional dysregulation.
Frequency-specific transcranial neuromodulation of oscillatory alpha power alters and predicts human visuospatial attention performance
Authors: Kemmerer S. K. , Sack A.T. , de Graaf T.A. , ten Oever S. , De Weerd P. , Schuhmann T.
Published: August 2020

Unilateral transcranial alternating current stimulation (tACS) at alpha frequency modulates the locus of spatial attention. However, the neural mechanisms by which tACS influences spatial attention remain poorly understood. Here, we applied high-definition tACS at the individual alpha frequency (IAF), two control frequencies (IAF+/-2Hz) and sham to the left posterior parietal cortex and measured its effects on visuospatial attention performance as well as alpha power (using electroencephalography, EEG). Our results revealed a leftward lateralization of alpha power relative to sham. At a high value of leftward alpha lateralization, we also observed a leftward attention bias, which differed from sham. Moreover, the magnitude of the alpha lateralization effect predicted the attention bias. These effects occurred for tACS at IAF but not for the control frequencies. This suggests that tACS operates through oscillatory interactions with ongoing brain rhythms in line with the synchronization theory. Our results also highlight the importance of personalized stimulation protocols, especially in potential clinical settings.
Current and future ocean chemistry negatively impacts calcification in predatory planktonic snails
Authors: Wall-Palmer Deborah , Mekkes Lisette , Ramos-Silva Paula , Dämmer Linda K. , Goetze Erica , Bakker Karel , Duijm Elza , Peijnenburg Katja T.C.A.
Published: August 2020

Planktonic gastropods mediate an important flux of carbonate from the surface to the deep ocean. However, we know little about the response of atlantid heteropods, the only predatory, aragonite shelled zooplankton, to ocean acidification (OA), and they are not incorporated in any carbonate flux models. Here we quantify the effects of OA on calcification and gene expression in atlantids across three pH scenarios: mid-1960’s, ambient, and future 2050 conditions. Atlantid calcification responses to decreasing pH were negative, but not uniform, across the three scenarios. Calcification was reduced from mid-1960s to ambient conditions, and longer shells were grown under 2050 conditions. Differential gene expression indicated a stress response at both ambient and future conditions, with down-regulation of growth and biomineralization genes with decreasing pH. Our results suggest that ocean chemistry in the South Atlantic is already limiting atlantid calcification, and that exposure to near-future OA triggers rapid shell growth under stress.
Estimation of Laminar BOLD Activation Profiles using Deconvolution with a Physiological Point Spread Function
Authors: Markuerkiaga Irati , Marques José P. , Gallagher Tara E. , Norris David G.
Published: August 2020

Background

The specificity of gradient echo (GE)-BOLD laminar fMRI activation profiles is degraded by intracortical veins that drain blood from lower to upper cortical layers, propagating activation signal in the same direction. This work describes an approach to obtain layer specific profiles by deconvolving the measured profiles with a physiological Point Spread Function (PSF).

New Method

It is shown that the PSF can be characterised by a TE-dependent peak to tail (p2t) value that is independent of cortical depth and can be estimated by simulation. An experimental estimation of individual p2t values and the sensitivity of the deconvolved profiles to variations in p2t is obtained using laminar data measured with a multi-echo 3D-FLASH sequence. These profiles are echo time dependent, but the underlying neuronal response is the same, allowing a data-based estimation of the PSF.

Results

The deconvolved profiles are highly similar to the gold-standard obtained from extremely high resolution 3D-EPI data, for a range of p2t values of 5-9, which covers both the empirically determined value (7.1) and the value obtained by simulation (6.3).

Comparison with Existing Method(s)

Corrected profiles show a flatter shape across the cortex and a high level of similarity with the gold-standard, defined as a subset of profiles that are unaffected by intracortical veins.

Conclusions

We conclude that deconvolution is a robust approach for removing the effect of signal propagation through intracortical veins. This makes it possible to obtain profiles with high laminar specificity while benefitting from the higher sensitivity and efficiency of GE-BOLD sequences.
Real-time, low-latency closed-loop feedback using markerless posture tracking
Authors: Kane Gary , Lopes Gonçalo , Saunders Jonny L. , Mathis Alexander , Mathis Mackenzie W.
Published: August 2020

The ability to control a behavioral task or stimulate neural activity based on animal behavior in real-time is an important tool for experimental neuroscientists. Ideally, such tools are noninvasive, low-latency, and provide interfaces to trigger external hardware based on posture. Recent advances in pose estimation with deep learning allows researchers to train deep neural networks to accurately quantify a wide variety of animal behaviors. Here we provide a newDeepLabCut-Live!package that achieves low-latency real-time pose estimation (within 15 ms, >100 FPS), with an additional forward-prediction module that achieves zero-latency feedback, and a dynamic-cropping mode that allows for higher inference speeds. We also provide three options for using this tool with ease: (1) a stand-alone GUI (calledDLC-Live! GUI), and integration into (2)Bonsaiand (3)AutoPilot. Lastly, we benchmarked performance on a wide range of systems so that experimentalists can easily decide what hardware is required for their needs.
Distinguishing Critical, Beneficial, Neutral and Harmful Mutations Uncovered in the Directed Evolution of a Yeast Membrane Receptor
Authors: Adeniran Adebola , Tyo Keith E.J.
Published: August 2020

We present a reversion analysis of mutations introduced during the directed evolution of the yeast G-protein coupled receptor (GPCR) Ste2p to detect a peptide biomarker of chronic kidney disease. Two mutated receptors are analyzed in this study. Mutations acquired during directed evolution were reverted one at a time to the wild-type residue to assess the mutation’s contribution to receptor function. Mutations in the first and fifth transmembrane regions, the second intracellular loop and a truncation were found to be crucial for sensitive detection of the peptide biomarker. Some mutations acquired during directed evolution were found to be neutral to or harmful for biomarker detection. Mutations were also assessed for their contributions to increasing basal activity of the evolved receptors. A similar set of crucial mutations were found in the two receptors, implying a similar mechanism detection. The mutations are reasoned to appear to give the ability to detect a smaller sized peptide, affect interaction with the G-protein and allow for prolonged signaling after stimulation. These data should provide guidance for further engineering of Ste2p and other GPCRs.
A Deep Learning Framework for Predicting Human Essential Genes by Integrating Sequence and Functional data
Authors: Zhang Xue , Xiao Weijia , Xiao Wangxin
Published: August 2020

Essential genes are necessary to the survival or reproduction of a living organism. The prediction and analysis of gene essentiality can advance our understanding to basic life and human diseases, and further boost the development of new drugs. Wet lab methods for identifying essential genes are often costly, time consuming, and laborious. As a complement, computational methods have been proposed to predict essential genes by integrating multiple biological data sources. Most of these methods are evaluated on model organisms. However, prediction methods for human essential genes are still limited and the relationship between human gene essentiality and different biological information still needs to be explored. In addition, exploring suitable deep learning techniques to overcome the limitations of traditional machine learning methods and improve the prediction accuracy is also important and interesting. We propose a deep learning based method, DeepSF, to predict human essential genes. DeepSF integrates sequence features derived from DNA and protein sequence data with features extracted or learned from different types of functional data, such as gene ontology, protein complex, protein domain, and protein-protein interaction network. More than 200 features from these biological data are extracted/learned which are integrated together to train a cost-sensitive deep neural network by utilizing multiple deep leaning techniques. The experimental results of 10-fold cross validation show that DeepSF can accurately predict human gene essentiality with an average AUC of 95.17%, the area under precision-recall curve (auPRC) of 92.21%, the accuracy of 91.59%, and the F1 measure about 78.71%. In addition, the comparison experimental results show that DeepSF significantly outperforms several popular traditional machine learning models (SVM, Random Forest, and Adaboost), and performs slightly better than a recent deep learning model (DeepHE). We have demonstrated that the proposed method, DeepSF, is effective for predicting human essential genes. Deep learning techniques are promising at both feature learning and classification levels for the task of essential gene prediction.