bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between diffuse idiopathic skeletal hyperostosis and fragility vertebral fracture: a prospective study in older men
Authors: Guiot Anaïs , Estublier Charline , Gaude Marine , Szulc Pawel , Chapurlat Roland
Published: July 2020

Objective

To analyse the risk of incident vertebral and non-vertebral fracture in men with DISH.

Methods

In 782 men ages 50–85 years, DISH was diagnosed using Resnick’s criteria. In men followed prospectively for 7.5 years, a radiographic incident vertebral fracture was defined by a decrease of ≥20% or ≥4mm in any vertebral height vs baseline. Self-reported incident non-vertebral fractures were confirmed by medical records.

Results

Men with DISH had higher BMD at the lumbar spine (P < 0.05), but not at other skeletal sites. After adjustment for confounders including disc space narrowing (DSN) and endplate irregularity, the risk of vertebral fracture was higher in men with DISH vs men without DISH [10/164 (6.1%) vs 16/597 (2.7%), P < 0.05; odds ratio (OR) 2.89 (95% CI 1.15, 7.28), P < 0.05]. DISH and low spine BMD were each associated with a higher vertebral fracture risk. The vertebral fracture risk was higher in men who had both DISH and severe DSN. DISH and endplate irregularities (EIs) were each associated with higher vertebral fracture risk. DISH, DSN and EIs define the intervertebral space dysfunction, which was associated with higher vertebral fracture risk [OR 3.99 (95% CI 1.45, 10.98), P < 0.01]. Intervertebral space dysfunction improved the vertebral fracture prediction (ΔAUC = +0.111, P < 0.05), mainly in men with higher spine BMD (>0.9 g/cm2; ΔAUC = +0.189, P < 0.001). DISH was not associated with the risk of non-vertebral fracture.

Conclusion

DISH is associated with higher vertebral fracture risk, independently of other risk factors. Assessment of the intervertebral space dysfunction components may improve the vertebral fracture prediction in older men.
REPEAT CHEST CT SCANS IN MODERATE-TO-SEVERE PATIENTS’ MANAGEMENT DURING THE COVID-19 PANDEMIC: OBSERVATIONS FROM A SINGLE CENTRE IN WUHAN, CHINA
Authors: Chen Lang , Wang Qiuxia , Wu Hongyu , Hu Junwu , Zhang Jing
Published: July 2020

Objective

To observe the rates of repeated computed tomographic scans (CTs) in a cohort of patients with coronavirus disease-2019 (COVID-19) and to assess the validity of repeat CTs.

Methods

Each CT was recorded, and the validity of the repeated CTs was assessed.

Results

The 394 patients underwent a total of 1493 CTs. Of the 394 patients, 260 received at least one non-value-added CT. Both the total number of CTs (median, 4; interquartile range (IQR), 3–5) and non-value-added CTs (median, 1; IQR, 0–1) per patient were strongly related to the disease duration (R2 = 0.566 for total CTs, R2 = 0.432 for non-value-added CTs, p < 0.001). The proportion of non-value-added CTs was potentially higher after 3 weeks from symptom onset (>35%).

Conclusions

There was a high rate of repeat CTs for the COVID-19 patients, and the proportion of non-value-added CTs increased with disease duration. Follow-up CT should be avoided without clinical decline.

Advances in Knowledge

As COVID-19 is impacting healthcare systems across the globe, we believe in our findings that serial chest CT imaging has limited clinical utility in basically stable COVID-19 patients, will help relieve some of this burden.
Construction of the concept of pairability in comparing infinite sets in the individuals’ mind: an APOS approach
Authors: Mahdiyan Mohadaseh , Barahmand Ali
Published: July 2020

This study focuses on the concept of pairability as a fundamental metaphorical concept in the Cantorian set theory regarding comparison of infinite sets. In this theory, pairability appears in a hierarchical manner of generating and developing as a one-to-one correspondence by arrows in finite, and then in infinite states, a bijection map through an explicit formula and the concept of cardinality. Adapting these hierarchical components of pairability and the APOS theory, about description of constructing and understanding a mathematical concept in a hierarchical manner, this study examines the construction of the concept of pairability in the individuals’ mind. In this way, their imaginations of pairability and practical performances in different situations will also be surveyed. In so doing, a total of 20 mathematics teachers and university lecturers holding at least an M.Sc. degree in mathematics were chosen. To collect the data, interviews were conducted in which the participants not only answered questions about the concept of the various types of pairability but also compared infinite countable sets in different situations. Our findings revealed that a bijection map via an explicit formula was the individuals’ dominant conception of pairability and most of the incorrect answers were related to unsuccessful attempts to recall a formula or method as the only possible way, and the encapsulated concept of cardinality was used less frequently in practice. Therefore, there was not a total schema of actions, processes and objects of the concept of pairability in the individuals’ mind.
Testing wastewater to detect severe acute respiratory syndrome coronavirus 2 in communities
Authors: Harries Anthony D , dar Berger Selma , Satyanarayana Srinath , Thekkur Pruthu , Kumar Ajay M V
Published: July 2020

Research groups around the world are starting to analyse whether wastewater surveillance is a useful tool to monitor the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in communities. Reported studies from the Netherlands, USA, Australia and France have demonstrated that SARS-CoV-2 can be detected and quantified in wastewater, allowing the total number of community infections to be estimated as well as monitoring whether the virus has returned to a community after elimination. Further work is required to improve the quantification of virus, to better detect the virus at low levels and to ensure wastewater samples are representative of the community under surveillance.
Oxygenation Strategy During Acute Respiratory Failure in Critically-Ill Immunocompromised Patients
Authors: Lemiale Virginie , De Jong Audrey , Dumas Guillaume , Demoule Alexandre , Mokart Djamel , Pène Frederic , Kouatchet Achille , Bisbal Magali , Bruneel Fabrice , Lebert Christine , Vinatier Isabelle , Benoit Dominique , Meert Anne-Pascale , Jaber Samir , Darmon Michael , Azoulay Elie
Published: July 2020

Objectives:

To assess the response to initial oxygenation strategy according to clinical variables available at admission.

Design:

Multicenter cohort study.

Setting:

Thirty French and Belgium medical ICU.

Subjects:

Immunocompromised patients with hypoxemic acute respiratory failure.

Interventions:

None.

Measurements and Main Results:

Data were extracted from the Groupe de Recherche en Reanimation Respiratoire du patient d'Onco-Hématologie database. Need for invasive mechanical ventilation was the primary endpoint. Secondary endpoint was day-28 mortality. Six-hundred forty-nine patients were included. First oxygenation strategies included standard oxygen (n = 245, 38%), noninvasive ventilation (n = 285; 44%), high-flow nasal cannula oxygen (n = 55; 8%), and noninvasive ventilation + high-flow nasal cannula oxygen (n = 64; 10%). Bilateral alveolar pattern (odds ratio = 1.67 [1.03–2.69]; p = 0.04), bacterial (odds ratio = 1.98 [1.07–3.65]; p = 0.03) or opportunistic infection (odds ratio = 4.75 [2.23–10.1]; p < 0.001), noninvasive ventilation use (odds ratio = 2.85 [1.73–4.70]; p < 0.001), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10–1.28]; p < 0.001), and ratio of Pao
2 and Fio
2 less than 100 at ICU admission (odds ratio = 1.96 [1.27–3.02]; p = 0.0002) were independently associated with intubation rate. Day-28 mortality was independently associated with bacterial (odds ratio = 2.34 [1.10–4.97]; p = 0.03) or opportunistic infection (odds ratio = 4.96 [2.11–11.6]; p < 0.001), noninvasive ventilation use (odds ratio = 2.35 [1.35–4.09]; p = 0.003), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10–1.28]; p < 0.001), and ratio of Pao
2 and Fio
2 less than 100 at ICU admission (odds ratio = 1.97 [1.26–3.09]; p = 0.003). High-flow nasal cannula oxygen use was neither associated with intubation nor mortality rates.

Conclusions:

Some clinical characteristics at ICU admission including etiology and severity of acute respiratory failure enable to identify patients at high risk for intubation.
Rise in Angiopoietin-2 Following Neonatal Cardiac Surgery Is Associated With Adverse Clinical Outcomes
Authors: Watkins Kimberly J. , Geisler Sarah , Doman Tammy , Orringer Matthew J. , Tracy Paloma , Yu Sunkyung , Wilder Nicole S. , Russell Mark W.
Published: July 2020

Objectives:

Neonatal cardiac surgery for congenital cardiac defects is associated with significant morbidity and mortality, and there is a need for early identification of patients at highest risk of adverse outcomes. Because vascular endothelial injury mediates damage across organ systems, we measured serum biomarkers of endothelial injury in neonates following cardiopulmonary bypass and examined their associations with short-term outcomes.

Design:

Prospective cohort study.

Setting:

Pediatric cardiac ICU.

Patients:

Thirty neonates less than 2 weeks old undergoing repair of congenital cardiac defects with cardiopulmonary bypass.

Interventions:

None.

Measurements and Main Results:

Biomarkers of endothelial integrity, angiopoietin-1 and angiopoietin-2, were measured preoperatively and at 24 hours postoperatively. A composite adverse outcome was defined as any of the following: stroke, need for renal replacement therapy, extracorporeal membrane oxygenation support, cardiac arrest, or death. Associations of biomarkers with adverse outcomes were examined using Wilcoxon rank-sum test. There was an increase in angiopoietin-2 from preoperatively to 24 hours postoperatively (p < 0.0001) and a decrease in angiopoietin-1 from preoperatively to 24 hours postoperatively (p < 0.0001). Patients with greater rise in angiopoietin-2 from preoperatively to 24 hours postoperatively had greater risk of composite adverse outcome (p = 0.04). They had a trend toward higher Vasoactive-Inotropic Score (p = 0.06) and a higher prevalence of low cardiac output syndrome (p = 0.06). Twenty-four hour postoperative angiopoietin-2 level was associated with the composite adverse outcome (p = 0.03). The rise in angiopoietin-2 level from preoperatively to 24 hours postoperatively directly correlated with cardiopulmonary bypass duration (r = 0.47; p = 0.01).

Conclusions:

In neonatal cardiac surgery, longer duration of cardiopulmonary bypass is directly associated with greater endothelial injury as measured by increased serum levels of angiopoietin-2. Angiopoietin-2 levels 24 hours postoperatively were significantly associated with a composite adverse outcome. Postoperative angiopoietin-2 level may serve as an early indicator of patients in need of closer monitoring and protective intervention. Further research into endothelial protective strategies is warranted.
Conditioning open-label placebo: a pilot pharmacobehavioral approach for opioid dose reduction and pain control
Authors: Morales-Quezada Leon , Mesia-Toledo Ines , Estudillo-Guerra Anayali , O'Connor Kevin C. , Schneider Jeffrey C. , Sohn Douglas J. , Crandell David M. , Kaptchuk Ted , Zafonte Ross
Published: July 2020

Introduction:

Opioid consumption for those in comprehensive inpatient rehabilitation units is high because of the complexity of their injuries. Notably, pain in rehabilitation leads to worsened clinical outcomes because of maladaptive behaviors and poor engagement during therapies. It is critical to developing evidence-based pharmacobehavioral interventions. Based on principles of classical conditioning, conditioning open-label placebo (COLP) is a promising approach for reducing opioid use in comprehensive inpatient rehabilitation, and this technique takes advantage of the possibility of association learning and opioid pharmacology to promote evoked placebo-driven analgesia.

Objectives:

In this brief report, we evaluate the feasibility of COLP as a pharmacobehavioral intervention to decrease total opioid consumption in patients with pain hospitalized at Spaulding Rehabilitation Hospital.

Methods:

Inpatients with spinal cord injury and polytrauma (n = 20) with moderate to severe pain were randomized to receive COLP (n = 10) or treatment-as-usual for 6 consecutive days. Opioid utilization was measured by morphine equivalents using the morphine equivalent dose conversion; pain severity was assessed using the numerical visual analog scale.

Results:

Conditioning open-label placebo significantly reduced total opioid consumption by the end of the intervention period (P ≤ 0.001). Pain reduction was also significant for the COLP group (P = 0.005), whereas the treatment-as-usual group demonstrated a trend towards pain reduction (P = 0.05).

Conclusions:

This study presents the first data in the use of a pharmacobehavioral intervention that capitalize on the benefits of open-label placebo and classical drug conditioning for opioid dose reduction in a population with moderate to severe pain exposed to intensive inpatient rehabilitation.
Description of Luteithermobacter gelatinilyticus gen. nov., sp. nov., and Paremcibacter congregatus gen. nov., comb. nov. via reclassification of the genus Emcibacter
Authors: Park Mi-Jeong , Namirimu Teddy , Yang Sung-Hyun , Kwon Kae Kyoung
Published: July 2020

Strain MEBiC09520T, which was isolated from a tidal sediment in Incheon, Korea, is a pale yellow, rod-shaped bacterium, cells of which are 0.4–0.5 µm in width and 1.5–2 µm in length. Strain MEBiC09520T shared 95.17 and 92.57% 16S rRNA gene sequence similarity with

Emcibacter nanhaiensis

and

E. congregatus

, respectively. It grew optimally at pH 6.0, at 55 °C and with 2.5–3.5% (w/v) NaCl. Its polar lipid components included phosphatidylethanolamine (PE), diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), an unidentified phospholipid (PL), three unidentified aminolipids (ALs) and two unidentified lipids (L). The fatty acids C16:0, C19:0 cyclo ω8c, C14:0 2-OH and summed feature 8 (C18:1ω7c and/or C18:1ω6c) were predominantly present in its cell wall. Strain MEBiC09520T was thermophilic, while

E. nanhaiensis

and

E. congregatus

were mesophilic. Although

E. nanhaiensis

showed no nitrate reduction activity, MEBiC09520T and

E. congregatus

showed a positive reaction. These strains differed in carbohydrate utilization. In particular,

E. congregatus

was able to thrive on various carbohydrate substrates as compared to the other strains. The average nucleotide identity value was 69.92% between strain MEBiC09520T and

E. congregatus

ZYLT, 70.38% between

E. congregatus

ZYLT and

E. nanhaiensis

HTCJW17T, and 72.83% between strain MEBiC09520 and

E. nanhaiensis

HTCJW17T. Considering these differences, strain MEBiC09520T (=KCCM 43320T=MCCC 1K03920T) is suggested to represent and novel species of a new genus, Luteithermobacter gelatinilyticus gen. nov., sp. nov., and

E. congregatus

should be reclassified as Paremcibacter congregatus gen. nov., comb. nov.
Mrakia stelviica sp. nov. and Mrakia montana sp. nov., two novel basidiomycetous yeast species isolated from cold environments
Authors: Turchetti Benedetta , Sannino Ciro , Mezzasoma Ambra , Zucconi Laura , Onofri Silvano , Buzzini Pietro
Published: July 2020

Five yeast strains were isolated from soil and sediments collected from Alps and Apennines glaciers during sampling campaigns carried out in summer 2007 and 2017, respectively. Based on morphological and physiological tests and on phylogenetic analyses reconstructed with ITS and D1/D2 sequences, the five strains were considered to belong to two related but hitherto unknown species within the genus Mrakia, in an intermediate position between Mrakia cryoconiti and Mrakia arctica. The names Mrakia stelviica (holotype DBVPG 10734T) and Mrakia montana (holotype DBVPG 10736T) are proposed for the two novel species and a detailed description of their morphological, physiological and phylogenetic features are presented. Both species fermented glucose, sucrose and trehalose, which is an uncommon feature in basidiomycetous yeasts, and showed septate hyphae with teliospore formation.
Hymenobacter ginkgonis sp. nov., isolated from bark of Ginkgo biloba
Authors: Cha Inseong , Kang Heeyoung , Kim Haneul , Bae Seokhyeon , Joh Kiseong
Published: July 2020

Strain HMF4947T, isolated from the bark of a ginkgo tree, was a pale-pink coloured, Gram-stain-negative, non-motile, strictly aerobic and rod-shaped bacterium. The isolate grew optimally on Reasoner's 2A agar at 30 °C, pH 7.0 and with 0 % NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain HMF4947T belonged to the genus

Hymenobacter

and was most closely related to

Hymenobacter metalli

A2-91T (96.9 % sequence similarity) and

Hymenobacter pomorum

9-2-1-1T (96.5 %). The average nucleotide identity and estimated DNA–DNA hybridization values between strain HMF4947T and

Hymenobacter arizonensis

DSM 17870T were 74.3 and 20.5 %, respectively. The major fatty acids were summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c), iso-C15 : 0 and C16 : 1
 ω5c. The predominant isoprenoid quinone was menaquinone-7. The polar lipids comprised phosphatidylethanolamine, one unidentified aminoglycolipid, three unidentified aminophospholipids, one unidentified phospholipid, three unidentified aminolipids, two unidentified glycolipids and three unidentified polar lipids. The genomic DNA G+C content was 59.3 mol%. Thus, based on phylogenetic, phenotypic and chemotaxonomic data, strain HMF4947T represents a novel species of the genus

Hymenobacter

, for which the name Hymenobacter ginkgonis sp. nov. is proposed. The type strain of the species is strain HMF4947T (=KCTC 72780T=NBRC 114271T).
Ciprofloxacin-induced persister-cells in Campylobacter jejuni
Authors: Ovsepian Armen , Larsen Marianne Halberg , Vegge Christina Skovgaard , Ingmer Hanne
Published: July 2020

Campylobacter jejuni

is a major bacterial foodborne-pathogen. Ciprofloxacin is an important antibiotic for the treatment of

C. jejuni

, albeit high rates of fluoroquinolone resistance have limited its usefulness. Persister-cells are transiently antibiotic-tolerant fractions of bacterial populations and their occurrence has been associated with recalcitrant and persistent bacterial infections. Here, time-kill assays with ciprofloxacin (200×MIC, 25 µg ml−1) were performed in

C. jejuni

strains 81–176 and RM1221 and persister-cells were found. The frequency of survivors after 8 h of ciprofloxacin exposure was approx. 10−3 for both strains, while after 22 h the frequency was between 10−5–10−7, depending on the strain and growth-phase. Interestingly, the stationary-phase cultures did not display more persister-cells compared to exponential-phase cultures, in contrast to what has been observed in other bacterial species. Persister-cells after ampicillin exposure (100×MIC, 200 µg ml−1) were not detected, implying that persister-cell formation in

C. jejuni

is antibiotic-specific. In attempts to identify the mechanism of ciprofloxacin persister-cell formation, stringent or SOS responses were not found to play major roles. Overall, this study reports ciprofloxacin persister-cells in

C. jejuni

and challenges the notion of persister-cells as plainly dormant non-growing cells.
Effect of storage conditions on the storage characteristics of
macarons
Authors: Park Young Mi , Kim Da Hee , Kim Su Jin , Kim Mee Ree
Published: July 2020

The purpose of this study was to evaluate the storage characteristics of macarons
following storage under a range of conditions. Thus, the macarons were stored
under three different sets of conditions, namely refrigeration (4°C),
room temperature defrosting after freezing (−20→25°C), and
refrigeration defrosting after freezing (−20→4°C), fillings
were added during freezing. The volume, moisture content, and texture of each
sample was determined, and sensory evaluations were conducted to identify the
quality characteristics during storage. More specifically, in the case of the
frozen samples, the volume was maintained at the beginning of the storage
period, while in the refrigerated sample, the volume was maintained in the
latter part of the storage period. In addition, the moisture content increased
under all three conditions, and after three weeks, the highest moisture content
was observed for the sample defrosted in the refrigerator after freezing.
Examination of the textual properties (i.e., hardness, chewiness, and gumminess)
showed increased values in the refrigerated sample, and reduced values in the
frozen samples, whereby defrosting in the refrigerator gave the lowest value. In
the sensory test, the overall acceptability was the highest for the sample
defrosted at room temperature, resulting in the highest scores relating to
color, nutty flavor, and nutty taste. Based on these results, it appears that
when long-term storage is required, freezing in the presence of filling is
considered optimal.
The validation of HPLC analytical method for Allium
hookeri Thwaites and Curcuma longa complex extract
as functional ingredients
Authors: Choi Eunjin , Oh Kyeo-nyeo , Hong Jiae , Jeong Changsik , Im Sojeng , Kim Cho-een , Lee Seul-gi , Choi Chulyung
Published: July 2020

This study was preformed to establish a simple and reliable HPLC/UV analytical
method to determine p-coumaric acid contents for the
standardization of water extracts of Allium hookeri and
Curcuma longa complex as functional health food
ingredients. The quantitative HPLC method was optimized using a reversed-phase
C18 column at 35°C with methanol and H2O
(30:70, v/v) as the gradient mobile phase at a flow rate of 1.0 mL/min and along
with detection wavelength of UV 300 nm. This HPLC/UV analytical method exhibited
good specificity and high linearity in the tested range of 1.0–10.0 mg/mL with
excellent coefficient of determination (R2) of 1.0. The limit of
detection and limit of quantification were 0.08 and 0.24 μg/mL,
respectively. In addition, the relative standard deviation values from the intra
and inter-day precision measurements were 0.4 and 0.1%, respectively.
These results indicate that the established HPLC/UV analytical method is simple,
specific, precise, accurate, and reproducible and so could be employed in the
quantitative analysis of p-coumaric acid as a functional
compound in Allium hookeri Thwaites and Curcuma
longa complex.
Antioxidant activity of coffee added with sword bean
Authors: Bae Hun Cheon , Kim Hae Seong , Kim Eun Hye , Moon Jae-Hak
Published: July 2020

Coffee is one of the most popular non-alcoholic beverages worldwide and is known to exhibit various beneficial therapeutic effects. Recently, studies on blending coffee, which contains added natural sources of biologically active compounds, have been published, with the aim of enhancing the health benefits of coffee-based beverages. For example, sword bean (SB) has been reported to exert various physiological activities and roasted SB is consumed as a coffee-like drink. Thus, we herein selected SB as a blending material to enhance the health function of coffee. SB-added coffee samples were prepared by mixing SB extract with coffee extract, and the antioxidant activities of the resulting mixtures were evaluated. The total phenolics content, DPPH radical-scavenging activity, reducing power, ABTS+ radical-scavenging activity, and hydroxyl radical-scavenging activity found to be directly proportional to the quantity of added SD extract. Moreover, inhibitory eﬀects on the formation of cholesteryl ester hydroperoxides in copper ion-induced rat blood plasma oxidation were observed even upon the oral administration of only a small quantity of SD-blended coffee. It was therefore suggested that SB exhibits potential for use as a blending material for coffee beverages, whereby the intake of SB-added coffee may have more beneficial health properties in vivo compared to the intake of coffee beverages alone.
Dynamic causal modeling of layered magnetoencephalographic event-related responses
Authors: Ihle Stephan J. , Bonaiuto James J. , Bestmann Sven , Stephan Klaas Enno , Barnes Gareth R. , Heinzle Jakob
Published: July 2020

The layered architecture of cortex is thought to play a fundamental role in shaping cortical computations. However, direct electrophysiological measurements of layered activity are not possible non-invasively in humans. Recent advances have shown that a distinction of two layers can be achieved using magnetoencephalography in combination with head casts and advanced spatial modeling. In this technical note, we present a dynamic causal model of a single cortical microcircuit that models event related potentials. The model captures the average dynamics of a detailed two layered circuit. It combines a temporal model of neural dynamics with a spatial model of a layer specific lead field to facilitate layer separation. In simulations we show that the spatial arrangement of the two layers can be successfully recovered using Bayesian inference. The layered model can also be distinguished from a single dipole model. We conclude that precision magnetoencephalography in combination with detailed dynamical system modeling can be used to study non-invasively the fast dynamics of layered computations.
BDdb: a comprehensive platform for exploration and utilization of birth defect multi-omics data
Authors: Zhang Dengwei , Sun Hai-Xi , Zhou Ziheng , Jiang Xiaosen , Chen Dongsheng , Zhou Si , Huang Jie , Qu Shoufang , Gu Ying , Zhang Xiuqing , Jin Xin , Gao Ya , Shen Yue , Chen Fang
Published: July 2020

Birth defect, not only poses a major challenge for infant health but also attracts the attention of countless people in the world. Chromosome abnormality directly results in diverse birth defects which are generally deleterious and even lethal. Therefore, gaining molecular regulatory insights into these diseases is important and necessary for effective prenatal screening. Recently, with the advance of next-generation sequencing (NGS) techniques, a myriad of treatises and data associated with these diseases are now constantly produced from different laboratories across the world. To meet the increasing requirements for birth-related data resources, we developed a birth defect multi-omics database (BDdb), freely accessible at http://t21omics.cngb.org and consisting of multi-omics data, circulating free DNA (cfDNA) data, as well as diseases biomarkers. Omics data sets from 138 GSE samples, 5271 GSM samples and 328 entries, and more than 2000 biomarkers of 22 birth-defect diseases in 5 different species were integrated into BDdb, which provides a user-friendly interface for searching, browsing and downloading selected data. Additionally, we re-analyzed and normalized the raw data so that users can also customize the analysis using the data generated from different sources or different High-Throughput Sequencing (HTS) methods. To our knowledge, BDdb is the first comprehensive database associated with birth-defect-related diseases. which would benefit the diagnosis and prevention of birth defects.
A phosphoproteomic approach reveals that PKD3 controls phenylalanine and tyrosine metabolism
Authors: Mayer Alexander E. , Loza-Valdes Angel , Schmitz Werner , Viera Jonathan Trujillo , Leitges Michael , Schlosser Andreas , Sumara Grzegorz
Published: July 2020

Members of the Protein Kinase D (PKD) family (PKD1, 2, and 3) integrate hormonal and nutritional inputs to regulate complex cellular metabolism. Despite the fact that a number of functions have been annotated to particular PKDs, their molecular targets are relatively poorly explored. PKD3 promotes insulin sensitivity and suppresses lipogenesis in the liver. However, its substrates are largely unknown. Here we applied proteomic approaches to determine PKD3 targets. We identified over three-hundred putative targets of PKD3. Among them phenylalanine hydroxylase (PAH). PAH catalyses the conversion of phenylalanine to tyrosine and its activity is regulated by, phenylalanine concentration and glucagon-induced signaling. Consistently, we showed that PKD3 is activated by glucagon and promotes tyrosine levels in primary hepatocytes and liver of mice.

Taken together, our comprehensive proteomic approach established that PKD3 determine the rate of phenylalanine to tyrosine conversion in the liver. Therefore, our data indicate that PKD3 might play a role in development of diseases related to the defective tyrosine and phenylalanine metabolism.
Natural selection and circular pathways to seasonal migration in birds
Authors: Halley Matthew R.
Published: July 2020

The “migratory revolutions” (MR) model is a synthetic theory of bird migration that seeks to explain the full range of the functional phenotype, from sedentary residents of non-seasonal (tropical) habitats to obligate long-distance migrants, as a cumulative evolutionary response to shifting distributions of adult extrinsic mortality across the annual cycle. At macroevolutionary scales, the general model predicts that migration evolves in circular patterns, reframing classic debates about the effects of migration on speciation and extinction rates. Here, I describe and apply the MR model to a well-known system, the passerine genusCatharus(Turdidae), to illustrate its broad implications for reconstructing evolutionary history.
Maternal age alters recombination rate inDrosophila pseudoobscura
Authors: Pownall Keeley A. , Taylor Hannah N. , Altindag Ulku H. , Stevison Laurie S.
Published: July 2020

As individuals senesce, factors correlated with fitness, such as fecundity and longevity, decline. Increased age also alters recombination rates in a variety of taxa. Changes in individual recombination rate, or ‘recombination rate plasticity’, can increase meiotic errors. InDrosophila melanogaster, multiple studies on maternal age and recombination rate have found a characteristic pattern where rates initially increase, then decrease, then increase again relative to controls. Here, this phenomenon was investigated inD. pseudoobscura. First, fecundity and survivorship were investigated to guide the choice of treatment age. Then, a large-scale recombination analysis (N=23,559) was set up using three X-linked phenotypic markers. Recombination rate differences in two genomic intervals were measured in females aged to 7 days (control) and 35 days (selected treatment age) prior to mating, with progeny collection continuing for 12 days post-mating in 72 hour timepoints. Results revealed a 3.39% increase in recombination rate due to maternal age (p=0.025), for the first 72 hour time point in one of the two marker intervals. For both genomic intervals, recombination rates were higher in the age treatment for the first time point and lower in later time points of the experiment. Next, these data were used to investigate crossover interference, which decreased with maternal age in the first time point and increased in the last time point. Overall, these results suggest that the mechanisms responsible for recombination rate plasticity may differ between maternal age and stressors, such as temperature.
Deep learning detection of informative features in tau PET for Alzheimer’s disease classification
Authors: Jo Taeho , Nho Kwangsik , Risacher Shannon L. , Saykin Andrew J. ,   for the Alzheimer’s Neuroimaging Initiative
Published: July 2020

Background

Alzheimer’s disease (AD) is the most common type of dementia, typically characterized by memory loss followed by progressive cognitive decline and functional impairment. Many clinical trials of potential therapies for AD have failed, and there is currently no approved disease-modifying treatment. Biomarkers for early detection and mechanistic understanding of disease course are critical for drug development and clinical trials. Amyloid has been the focus of most biomarker research. Here, we developed a deep learning-based framework to identify informative features for AD classification using tau positron emission tomography (PET) scans.

Methods

We analysed [18F]flortaucipir PET image data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. We first developed an image classifier to distinguish AD from cognitively normal (CN) older adults by training a 3D convolutional neural network (CNN)-based deep learning model on tau PET images (N=132; 66 CN and 66 AD), then applied the classifier to images from individuals with mild cognitive impairment (MCI; N=168). In addition, we applied a layer-wise relevance propagation (LRP)-based model to identify informative features and to visualize classification results. We compared these results with those from whole brain voxel-wise between-group analysis using conventional Statistical Parametric Mapping (SPM12).

Results

The 3D CNN-based classification model of AD from CN yielded an average accuracy of 90.8% based on five-fold cross-validation. The LRP model identified the brain regions in tau PET images that contributed most to the AD classification from CN. The top identified regions included the hippocampus, parahippocampus, thalamus, and fusiform. The LRP results were consistent with those from the voxel-wise analysis in SPM12, showing significant focal AD associated regional tau deposition in the bilateral temporal lobes including the entorhinal cortex. The AD probability scores calculated by the classifier were correlated with brain tau deposition in the medial temporal lobe in MCI participants (r=0.43 for early MCI and r=0.49 for late MCI).

Conclusion

A deep learning framework combining 3D CNN and LRP algorithms can be used with tau PET images to identify informative features for AD classification and may have application for early detection during prodromal stages of AD.
Real-time IP-10 measurements as a new tool for inflammation regulation within a clinical decision support protocol for managing severe COVID-19 patients
Authors: Lev Shaul , Gottesman Tamar , Levin Gal Sahaf , Lederfein Doron , Berkov Evgeny , Diker Dror , Zaidman Aliza , Nutman Amir , Ber Tahel Ilan , Angel Alon , Kellerman Lior , Barash Eran , Navon Roy , Boico Olga , Israeli Yael , Rosenberg Michal , Gelman Amir , Kalfon Roy , Simon Einav , Avni Noa , Hainrichson Mary , Zarchin Oren , Gottlieb Tanya M. , Oved Kfir , Eden Eran , Tadmor Boaz
Published: July 2020

The challenge of treating severely ill COVID-19 patients is particularly great due to the need to simultaneously manage oxygenation and the inflammatory state without compromising viral clearance. Currently, there are many tools to aid in oxygen management and in monitoring viral replication. However, predictive biomarkers for monitoring the host immune response across COVID-19 disease stages and specifically, for titrating immunomodulatory therapy are lacking. We utilized a recently cleared platform (MeMed Key™) that enables rapid and easy serial measurement of IP-10, a host protein implicated in lung injury due to viral-induced hyperinflammation. A dynamic clinical decision support protocol was employed for managing SARS-CoV-2 positive patients admitted to a COVID-19 dedicated medical center run by Clalit Health Services. This is the first protocol to include real-time measurements of IP-10 as a potential aid for regulating inflammation. Overall, 502 serial real-time IP-10 measurements were performed on 52 patients recruited between 7th April 2020 to 10th May 2020, with 12 patients admitted to the intensive care unit (ICU). IP-10 levels correlated with increased COVID-19 severity score and ICU admission. Within the ICU admitted patients, the number of days with IP-10 measurements >1,000 pg/ml was associated with mortality. Upon administration of corticosteroid immunomodulatory therapy, a significant decrease in IP-10 levels was observed. Real-time IP-10 monitoring represents a new tool to aid in management and therapeutic decisions relating to the inflammatory status of COVID-19 patients.
EEG-Beats: Automated analysis of heart rate variability (HVR) from EEG-EKG
Authors: Thanapaisal Supakjeera , Mosher Sabrina , Trejo Brenda , Robbins Kay
Published: July 2020

Heart rate variability (HRV), the variation of the period between consecutive heartbeats, is an established tool for assessing physiological indicators such as stress and fatigue. In non-clinical settings, HRV is often computed from signals acquired using wearable devices that are susceptible to strong artifacts. In EEG (electroencephalography) experiments, these devices must be synchronized with the EEG and typically provide intermittent interbeat interval information based on proprietary artifact-removal algorithms. This paper describes an automated algorithm that uses the output of an EEG sensor mounted on a subject’s chest to accurately detect interbeat intervals and to calculate time-varying metrics. The algorithm is designed for raw signals and is robust to artifacts, resulting in fine-grained capture of HRV that is synchronized with the EEG. An open-source MATLAB toolbox (EEG-Beats) is available to calculate interbeat intervals and many standard HRV time and frequency indicators. EEG-Beats is designed to run in a completely automated fashion on an entire study without manual intervention. The paper applies EEG-Beats to EKG signals measured with an EEG sensor in a large longitudinal study (17 subjects, 6 tasks, 854 datasets). The toolbox is available athttps://github.com/VisLab/EEG-Beats.
Phylogenetic Analysis Of SARS-CoV-2 In The First Months Since Its Emergence
Authors: Pereson Matías J. , Mojsiejczuk Laura , Martínez Alfredo P. , Flichman Diego M. , Garcia Gabriel H. , Di Lello Federico A.
Published: July 2020

During the first months of SARS-CoV-2 evolution in a new host, contrasting hypotheses have been proposed about the way the virus has evolved and diversified worldwide. The aim of this study was to perform a comprehensive evolutionary analysis to describe the human outbreak and the evolutionary rate of different genomic regions of SARS-CoV-2.

The molecular evolution in nine genomic regions of SARS-CoV-2 was analyzed using three different approaches: phylogenetic signal assessment, emergence of amino acid substitutions, and Bayesian evolutionary rate estimation in eight successive fortnights since the virus emergence.

All observed phylogenetic signals were very low and trees topologies were in agreement with those signals. However, after four months of evolution, it was possible to identify regions revealing an incipient viral lineages formation despite the low phylogenetic signal, since fortnight 3. Finally, the SARS-CoV-2 evolutionary rate for regions nsp3 and S, the ones presenting greater variability, was estimated to values of 1.37 × 10−3and 2.19 × 10−3substitution/site/year, respectively.

In conclusion, results obtained in this work about the variable diversity of crucial viral regions and the determination of the evolutionary rate are consequently decisive to understand essential feature of viral emergence. In turn, findings may allow characterizing for the first time, the evolutionary rate of S protein that is crucial for vaccines development.
What’s the Temperature in Tropical Caves?
Authors: Mejía-Ortíz Luis , Christman Mary C , Pipan Tanja , Culver David C
Published: July 2020

Hourly temperature was measured for approximately one year at 17 stations in three caves in Quintana Roo, Mexico. Thirteen of these stations were in the extensive twilight zones of all three caves. All seventeen stations showed seasonality in temperature with a 3 °C drop during the Nortes season. Two of the caves, Muévelo Sabrosito and Muévelo Rico, showed greater variability during the winter months while in Rio Secreto variability was greatest during the rainy season. Río Secreto is less open to the surface than the other two. All sites also showed a daily temperature cycle, although it was very faint in some Rio Secreto sites. While temperature variability is diminished relative to surface variation, its temporal pattern is worthy of further study.
Deep neural network models of sound localization reveal how perception is adapted to real-world environments
Authors: Francl Andrew , McDermott Josh H.
Published: July 2020

Mammals localize sounds using information from their two ears. Localization in real-world conditions is challenging, as echoes provide erroneous information, and noises mask parts of target sounds. To better understand real-world localization we equipped a deep neural network with human ears and trained it to localize sounds in a virtual environment. The resulting model localized accurately in realistic conditions with noise and reverberation, outperforming alternative systems that lacked human ears. In simulated experiments, the network exhibited many features of human spatial hearing: sensitivity to monaural spectral cues and interaural time and level differences, integration across frequency, and biases for sound onsets. But when trained in unnatural environments without either reverberation, noise, or natural sounds, these performance characteristics deviated from those of humans. The results show how biological hearing is adapted to the challenges of real-world environments and illustrate how artificial neural networks can extend traditional ideal observer models to real-world domains.
ChemEnv: a fast and robust coordination environment identification tool
Authors: Waroquiers David , George Janine , Horton Matthew , Schenk Stephan , Persson Kristin A. , Rignanese Gian-Marco , Gonze Xavier , Hautier Geoffroy
Published: July 2020

Coordination or local environments have been used to describe, analyze and understand crystal structures for more than a century. Here, a new tool called ChemEnv, which can identify coordination environments in a fast and robust manner, is presented. In contrast to previous tools, the assessment of the coordination environments is not biased by small distortions of the crystal structure. Its robust and fast implementation enables the analysis of large databases of structures. The code is available open source within the pymatgen package and the software can also be used through a web app available on http://crystaltoolkit.org through the Materials Project.
Mechanical behavior and phase change of alkali-silica reaction products under hydrostatic compression
Authors: Geng Guoqing , Shi Zhenguo , Leemann Andreas , Glazyrin Konstantin , Kleppe Annette , Daisenberger Dominik , Churakov Sergey , Lothenbach Barbara , Wieland Erich , Dähn Rainer
Published: July 2020

Alkali-silica reaction (ASR) causes severe degradation of concrete. The mechanical property of the ASR product is fundamental to the multiscale modeling of concrete behavior over the long term. Despite years of study, there is a lack of consensus regarding the structure and elastic modulus of the ASR product. Here, ASR products from both degraded field infrastructures and laboratory synthesis were investigated using high-pressure X-ray diffraction. The results unveiled the multiphase and metastable nature of ASR products from the field. The dominant phase undergoes permanent phase change via collapsing of the interlayer region and in-planar glide of the main layer, under pressure >2 GPa. The bulk moduli of the low- and high-pressure polymorphs are 27±3 and 46±3 GPa, respectively. The laboratory-synthesized sample and the minor phase in the field samples undergo no changes of phase during compression. Their bulk moduli are 35±2 and 76±4 GPa, respectively. The results provide the first atomistic-scale measurement of the mechanical property of crystalline ASR products.
One Mission, Multiples roads: Arvind eye care System in 2009
Authors: Manikutty S.
Published: July 2020

This case, “One Mission, Multiple Roads: Aravind Eyecare System in 2009” is a sequel to the earlier case, “Aravind Eyecare System: Giving Them the Most Precious Gift” (BP 0299). It describes the new challenges facing AECS in 2009. It presents the strategic choices facing a mission driven organization like AECS. For its future growth it had the option of several paths. Following any of these paths would not dilute its mission and yet it could not pursue all of them at the same time. It would have to prioritize them. The case encourages participants to develop criteria for this prioritization.
BAJAJ-TVS Patent Dispute
Authors: Agarwal Anurag K.
Published: July 2020

The case discusses the legal journey of the Bajaj — TVS patent dispute from the Madras High Court to the Supreme Court and back to the Madras High Court. Almost four years have passed, yet the final verdict is nowhere in sight. The Supreme Court has recommended a period of four months for such cases to be finally decided. In such instances, the warring parties either settle it out of court or adopt other means to do business. The value of patent is undermined if the patentee has to fight so much for its protection.
Arihant Retail, Chennai
Authors: Manikutty S
Published: July 2020

The case deals with Arihant Retail, a family business firms located at Chennai in Tamil Nadu, India. It is a small scale firm, with a turnover of ‘340 million in 2009–10. Mr. Vishal Surana, the young Chief Executive of Arihant, dreams of making this into a ‘3 billion store by 2015. He has a concept named “Hot Male”, a chain of stores stocking trendy fashionwear targeted at the “funky” young generation belonging to the SEC (Socio Economic Classification) “B” group. He is excited about it, and thinks he can build a whole new concept and grow based mainly on these “Hot Male” stores. Being a family firm, however, he has to take into consideration the views of his family members (they do not seem to interfere in any way) and family friends of long standing, who have their own views. The case outlines the broad options available to Vishal taking into account the business logic, the family logic, and the top management aspirations.
Howzzat?
Authors: Barua Samir K. , Balasubramanian N.
Published: July 2020

The game of cricket that originated in Britain thrives on passion and the following it generates in India and other South Asian countries is tremendous. The Board of Control for Cricket in India (BCCI) is the apex governing body that controls all cricketing events in the India. Being the richest such body, BCCI is the most powerful national body among similar organizations across countries where cricket is played. The world of cricket saw a sea change with the introduction of the Indian Premier League (IPL) due to its unprecedented commercial success. The case describes the betting scandal that hit IPL, BCCI and its promoter in the middle of 2013. The scandal involved the son-in-law of the President of BCCI. The events following the scandal saw the Supreme Court of India, the highest judicial body in the country, to indict BCCI and its President of serious misgovernance. Set in this backdrop, the case highlights governance issues in the functioning of not for profit organizations such as BCCI. The case provides an opportunity to reflect on and discuss as to how such quasi-public bodies ought to be governed.