bluuebunny/crossref_metadata_2025 huggingface dataset:
Breast Awareness, Self-Reported Abnormalities, and Breast Cancer in Rural Ethiopia: A Survey of 7,573 Women and Predictions of the National Burden
Authors: Ayele Wondimu , Addissie Adamu , Wienke Andreas , Unverzagt Susanne , Jemal Ahmedin , Taylor Lesley , Kantelhardt Eva J.
Published: March 2021

Background

Breast cancer (BC) is the most frequently diagnosed cancer and leading cause of cancer deaths among women in low-income countries. Ethiopia does not have a national BC screening program, and over 80% of patients are diagnosed with advanced stage disease. The aim of this study was to assess how many women self-report a breast abnormality and to determine their diagnoses in rural Ethiopia.

Methods

A community-based cross-sectional study was conducted among 7,573 adult women. Women were interviewed and educated about breast awareness, and those who reported breast abnormalities underwent clinical examination by experienced surgeons. Ultrasound-guided fine needle aspiration cytology (FNAC) was obtained, and cytological analysis was performed. The findings were projected to the female population of Ethiopia to estimate current and future burden of diseases.

Findings

Of the 7,573 women surveyed, 258 (3.4%) reported a breast abnormality, 246 (3.2%) received a physical examination, and 49 (0.6%) were found to be eligible for ultrasound-guided FNAC or nipple discharge evaluation. Of all the cases, five (10.2%) breast malignancies were diagnosed. We projected for Ethiopia that, approximately, 1 million women could self-report a breast abnormality, 200,000 women could have a palpable breast mass, and 28,000 women could have BC in the country.

Conclusion

The health care system needs to build capacity to assess and diagnose breast diseases in rural areas of Ethiopia. These data can be used for resource allocation to meet immediate health care needs and to promote detecting and treating BC at earlier stages of disease.

Implications for Practice

Routine mammography screening in a resource-limited country with a young population is neither sensitive nor affordable. Clinical breast examination with consecutive ultrasound-guided fine needle aspiration cytology may ensure early diagnosis, downstage disease, and reduce breast cancer mortality. This study had the unique opportunity to educate over 7,573 rural women about breast abnormalities and offer clinical and cytological diagnosis for reported breast abnormalities. The findings were extrapolated to show the nationwide burden of breast abnormalities and unmet diagnostic needs. These data will serve as policy guide to improve adequate referral mechanisms and breast diagnostic and treatment facilities.
Plasmonic properties of nanohybrids made of metallic nanoring and benzene molecules
Authors: Mokkath Junais Habeeb
Published: March 2021

Plasmon‐molecule coupling has recently been attracted great research interest in material science and quantum optics with a multitude of potential applications. In this work, using the linear combination of atomic orbitals real‐time‐propagation rt‐time dependent density functional theory (TDDFT) technique (LCAO‐rt‐TDDFT) and transition contribution maps, we investigate the optical and plasmonic features of a hybrid nanosystem comprising an elliptical‐shaped metal nanoring (ENR) and a couple of benzene molecules (located in close proximity at both sides of the ENR short axis and/or long axis). We find that pristine ENR exhibits localized surface plasmon resonances (LSPRs) and plasmon‐molecule coupling in hybrid nanosystems is highly sensitive to the location of the molecules. More specifically, when benzene molecules are placed at both sides of the ENR short axis, the dominant peak in the photoabsorption spectrum sustains its LSPR features with a significant enhancement in intensity. On the other hand, in an alternative situation where benzene molecules are placed at both sides of the ENR long axis, the dominant peak in the photoabsorption spectrum splits into three with diminishing LSPR features.
Energy allocation for activity recognition in wearable devices with kinetic energy harvesting
Authors: Xiao Ling , Meng Yu , Tian Xiaobing , Luo Haibo
Published: March 2021

Harvesting kinetic energy from body movement is regarded as a promising rechargeable energy source for wearable devices with low‐power. Energy allocation is essential for motion‐based rechargeable devices since the great variability of energy gained from movement. Based on the realistic characteristics of an ultra‐low‐power wearable devices and our measurement observations, we propose the optimization framework allocating energy to maximize the average accuracy of human activity recognition and provide an offline and online algorithm, respectively. We evaluate the proposed energy allocation approach with real‐world human activity and kinetic energy harvesting datasets. Experimental results validate that our proposed energy allocation approach can maximize the energy allocation utility and improve energy efficiency of wearable devices.
Prevalence and associated risk factors of Bovine mastitis in dairy cows in and around Assosa town, Benishangul‐Gumuz Regional State, Western Ethiopia
Authors: Tezera Melak , Aman Ali Endris
Published: March 2021

Background

Mastitis, a complex disease of multifactorial aetiology, is one of the most costly diseases in the dairy industry worldwide. It can be categorized as clinical and subclinical type relying on the clinical sign. The objectives of the study were to determine the prevalence of mastitis and to identify its intrinsic and extrinsic risk factors in dairy cows in and around Assosa town, Western Ethiopia.

Methods

A cross‐sectional study design was followed to address the objectives of the study. A total of 367 lactating cows were selected using simple random and systematic sampling techniques. Thorough clinical examination and California Mastitis Test (CMT) were deployed for detection of both clinical and subclinical mastitis, respectively.

Results

Based on CMT result and clinical examination the cow level prevalence of mastitis was 40.3% (n = 148), of which 11.99% (n = 44) and 28.34% (n = 104) were clinical and subclinical mastitis respectively. The corresponding quarter‐level prevalence was determined to be 26.9% (n = 394), comprising 11.99% (n = 176) clinical and 14.85% (n = 218) subclinical mastitis. The Chi‐square analysis of intrinsic risk factors revealed statistically significant differences (p <.05) in the prevalence of mastitis among breed, stage of lactation and body condition score. Likewise, production system, previous mastitis exposure, hygiene practice and type of floor were extrinsic risk factors significantly associated with the occurrence of mastitis.

Conclusions

In general, this study revealed a high prevalence of bovine mastitis in the study area. Thus, the current study shows the need for applying feasible mastitis intervention strategy with special emphasis on sub‐clinical mastitis and associated risk factors.
Defect extremal surface as the holographic counterpart of Island formula
Authors: Deng Feiyu , Chu Jinwei , Zhou Yang
Published: March 2021

Abstract

We propose defect extremal surface as the holographic counterpart of boundary quantum extremal surface. The defect extremal surface is defined by minimizing the Ryu-Takayanagi surface corrected by the defect theory. This is particularly interesting when the RT surface crosses or terminates on the defect. In a simple set up of AdS/BCFT, we find that the defect extremal surface formula gives precisely the same results of the boundary quantum extremal surface. We provide a decomposition procedure of an AdS bulk with a defect brane to see clearly how quantum extremal surface formula emerges from a brane world system with gravity glued to a flat space quantum field theory.
Self‐management Behaviors and Anthropometric Indices after Roux‐en‐Y Gastric Bypass
Authors: Sobhani Zahra , Amini Masood , Zarnaghash Maryam , Foroutan Hamid Reza , Mojab Seyed Vahid , Khazraei Hajar , Hosseini Seyed Vahid
Published: March 2021

Background

The aim of this study was to correlate the connection between self‐management behaviors and anthropometric indices after Roux‐en‐Y gastric bypass (RYGB).

Methods

A sample of 180 patients suffering from obesity were treated with RYGB in 2019; 6 and 18 months after surgery, anthropometric indices, including weight, waist circumference, waist‐ to‐height ratio, body mass index (BMI), and waist‐to‐hip ratio, were gauged, and participants completed the post‐bariatric surgery self‐management behaviors questionnaire.

Results

Correlation matrix results showed that all anthropometric indices had a significant positive relationship with self‐management behaviors after RYGB; the results of the 18‐month post‐surgical follow‐up exhibited no significant difference between anthropometric indices and self‐management behaviors, 6 and 18 months after surgery.

Conclusion

Therefore, the more self‐management behaviors increase, the greater decrease in anthropometric indices will happen after RYGB.
A behavioral task for exploring dynamics of communication system in dilemma situations
Authors: Inoue Naoki , Morita Junya
Published: March 2021

This research proposes a behavioral task to demonstrate the process of evolution of human communication systems based on the Machiavellian intelligence hypothesis, claiming that human sophisticated social intelligence such as linguistic ability has been formed through behaviors that maximize self-interest in a competitive social situation. The proposed task was designed as a dilemma game involving messaging to establish Machiavellian communication. The game was developed based on experimental semiotics, a method that generates novel artificial language and examines language functions. Through the proposed task, pairs of participants attach meanings to arbitral graphic symbols forming novel communication systems. In case studies using this task, participants modified or ambiguated the communication system by means of a dilemma between sharing and monopolizing rewards. The result suggests that the proposed game causes ambiguation of the communication system that functions equivocally.
The second Hankel determinant for strongly convex and Ozaki close-to-convex functions
Authors: Sim Young Jae , Lecko Adam , Thomas Derek K.
Published: March 2021

Let f be analytic in the unit disk $${\mathbb {D}}=\{z\in {\mathbb {C}}:|z|<1 \}$$

D
=
{
z
∈
C
:
|
z
|
<
1
}

, and $${{\mathcal {S}}}$$
S
be the subclass of normalized univalent functions given by $$f(z)=z+\sum _{n=2}^{\infty }a_n z^n$$

f

(
z
)

=
z
+

∑

n
=
2

∞

a
n

z
n

for $$z\in {\mathbb {D}}$$

z
∈
D

. We give sharp bounds for the modulus of the second Hankel determinant $$ H_2(2)(f)=a_2a_4-a_3^2$$

H
2

(
2
)

(
f
)

=

a
2

a
4

-

a
3
2

for the subclass $$ {\mathcal F_{O}}(\lambda ,\beta )$$

F
O

(
λ
,
β
)

of strongly Ozaki close-to-convex functions, where $$1/2\le \lambda \le 1$$

1
/
2
≤
λ
≤
1

, and $$0<\beta \le 1$$

0
<
β
≤
1

. Sharp bounds are also given for $$|H_2(2)(f^{-1})|$$

|

H
2

(
2
)

(

f

-
1

)

|

, where $$f^{-1}$$

f

-
1

is the inverse function of f. The results settle an invariance property of $$|H_2(2)(f)|$$

|

H
2

(
2
)

(
f
)

|

and $$|H_2(2)(f^{-1})|$$

|

H
2

(
2
)

(

f

-
1

)

|

for strongly convex functions.
Effects of Ageing on Aortic Circulation During Atrial Fibrillation; a Numerical Study on Different Aortic Morphologies
Authors: Deyranlou Amin , Miller Christopher A. , Revell Alistair , Keshmiri Amir
Published: March 2021

Atrial fibrillation (AF) can alter intra-cardiac flow and cardiac output that subsequently affects aortic flow circulation. These changes may become more significant where they occur concomitantly with ageing. Aortic ageing is accompanied with morphological changes such as dilation, lengthening, and arch unfolding. While the recognition of AF mechanism has been the subject of numerous studies, less focus has been devoted to the aortic circulation during the AF and there is a lack of such investigation at different ages. The current work aims to address the present gap. First, we analyse aortic flow distribution in three configurations, which attribute to young, middle and old people, using geometries constructed via clinical data. We then introduce two transient inlet flow conditions representative of key AF-associated defects. Results demonstrate that both AF and ageing negatively affect flow circulation. The main consequence of concomitant occurrence is enhancement of endothelial cell activation potential (ECAP) throughout the vascular domain, mainly at aortic arch and descending thoracic aorta, which is consistent with some clinical observations. The outcome of the current study suggests that AF exacerbates the vascular defects occurred due to the ageing, which increases the possibility of cardiovascular diseases per se.
Correction to: The Inhibitory Effect of Political Conservatism on Consumption: The Case of Fair Trade
Authors: Usslepp Thomas , Awanis Sandra , Hogg Margaret K , Daryanto Ahmad
Published: March 2021

A correction to this paper has been published: https://doi.org/10.1007/s10551-021-04780-w
Coatings with recycled polyvinyl butyral on polyester and polyamide mono- and multifilament yarns
Authors: Brendgen Rike , Graßmann Carsten , Grethe Thomas , Mahltig Boris , Schwarz-Pfeiffer Anne
Published: March 2021

Polyvinyl butyral is used in safety glass interlayers, mainly in car windshields. Legislative regulations require a recycling of cars after their lifetime and therefore also their safety glass. This causes the availability of recycled polyvinyl butyrate (r-PVB) originated from safety glass interlayers. Due to deteriorated optical properties, such as the transparency, and unknown amounts of plasticizers, it is challenging to reuse the recycled material in new windshields. Therefore, it is of particular interest to find new fields of application for r-PVB, such as the usage as a textile coating. In this research, r-PVB was investigated as a material for yarn coating. Polyester and polyamide mono- and multifilament yarns were coated continuously with solely a polymer dispersion and with mixtures of crosslinking agent and polymer dispersion. Crosslinked r-PVB coatings showed enhanced properties toward abrasion and chemical resistance. Coatings without the crosslinking agent showed a diminished abrasion resistance and could be washed off with ethanol. Mechanical properties of the monofilaments were influenced by the r-PVB coating in general. However, varying concentrations of the crosslinking agent did not affect the mechanical properties.
Relationship Between Thyroid Hormonal Status in Patients with a Hypothyroid Form of Hashimoto’s Thyroiditis and Iodine Concentrations in Drinking Water
Authors: Kasiyan Olha , Tkachenko Halyna , Kurhaluk Natalia , Yurchenko Svitlana , Manenko Alek
Published: March 2021

The current study aimed to identify correlative and regressive dependencies between the water iodine concentration and the levels of TSH (thyroid-stimulating hormone), thyroglobulin antibodies (TgAbs), and thyroid peroxidase (TPOAb) in the serum of 168 in patients (34 men and 134 women) with a hypothyroid form of Hashimoto’s thyroiditis who use water from the supply network and individual wells. Based on the water iodine concentration, low and moderate degrees of iodine endemia in the location of the patients were determined. In the groups of men and women using water from different water supply sources, there were direct correlations between the water iodine concentrations and the TgAbs and TPOAb titers as well as an inverse dependence between iodine and TSH levels. Multivariate regressive analysis indicated that TgAb and TSH in the group of women using water from a supply network and TPOAb titers in the group of women using well water were independent factors associated with water iodine concentrations. Statistically significant correlations and regressive dependencies between the water iodine concentrations and the biomarkers of the thyroid status of the patients indicate the risk of Hashimoto’s thyroiditis progression, especially among women with additional iodine intake.
Systematic Review and Meta-analysis on the Association of Occupational Exposure to Free Crystalline Silica and Rheumatoid Arthritis
Authors: Morotti A. , Sollaku I. , Franceschini F. , Cavazzana I. , Fredi M. , Sala E. , De Palma G.
Published: March 2021

Key messages

• Occupational exposure to free crystalline silica and tobacco smoking are associated with an increased risk rheumatoid arthritis, with the evidence of an interaction in seropositive subjects.

• Further studies in the field are needed to support such association

We carried out a systematic search for all published epidemiological studies concerning the association between occupational exposure to free crystalline silica (FCS) and subsequent development of rheumatoid arthritis (RA). A meta-analysis was conducted on relevant studies. We searched PubMed and Embase, search engines, for original articles published (from 1960 to November 2019) in any language. In addition, we also searched reference lists of included studies manually for additional relevant articles. Finally, twelve studies were included in the meta-analysis (seven case-control cases and five cohort studies). The odds risks and 95% confidence interval (CI) were calculated using a random effect meta-analysis. A primary meta-analysis (using a random effect model)—regarding RA risk in subjects exposed to FCS—yelled to an overall OR of 1.94 (95% CI 1.46–2.58). We also conducted three further meta-analysis, taking into account the presence of autoantibodies (anti-RF or anti-ACPA) and smoking habits and found a significant association between FCS and RA in both seropositive and seronegative subjects (OR 1.74, 95% CI 1.35–2.25 and OR 1.23, 95% CI 1.06–1.4, respectively) and in seropositive subjects which were smokers (OR 3.30, 95% CI 2.40–4.54). The studies that have investigated the association between RA and occupatational exposure to FCS are still scarce and the heterogeneity between the studies remains high. Some critical limitations have been identified within studies, among which, the methods for assessing exposure stand out. Although with due caution, our results confirm the hypothesis of an association between occupational exposure to FCS and RA development. There was an interaction between FCS and tobacco smoking in RA seropositive workers.
Secondary Hematoma Evacuation and Outcome After Initial Conservative Approach for Patients with Cerebellar Hematoma Larger than 3 cm
Authors: Singh Sanjula D. , Schreuder Floris H. B. M. , van Nieuwenhuizen Koen M. , Jolink Wilmar M. , Senff Jasper R. , Goldstein Joshua N. , Boogaarts Jeroen , Klijn Catharina J. M. , Rinkel Gabriel J. E. , Brouwers H. Bart
Published: March 2021

Background

In patients with spontaneous cerebellar intracerebral hemorrhage (ICH) guidelines advocate evacuation when the hematoma diameter is > 3 cm. We studied outcome in patients with cerebellar ICH > 3 cm who did not undergo immediate hematoma evacuation.

Methods

We included consecutive patients with cerebellar ICH > 3 cm at two academic hospitals between 2008 and 2017. Patients who died < 24 h (h) were excluded because of probable confounding by indication. We determined patient characteristics, hematoma volumes, EVD placement, secondary hematoma evacuation, in-hospital and 3-month case-fatality, and functional outcome.

Results

Of 130 patients with cerebellar ICH, 98 (77%) had a hematoma > 3 cm of whom 22 (23%) died < 24 h and 28 (29%) underwent hematoma evacuation < 24 h. Thus, 48 patients were initially treated conservatively (mean age 70 ± 13, 24 (50%) female). Of these 48 patients, 7 (15%) underwent secondary hematoma evacuation > 24 h, of whom 1 (14%) had received an EVD < 24 h. Five others also received an EVD < 24 h without subsequent hematoma evacuation. Of the 41 patients without secondary hematoma evacuation, 11 (28%) died and 20 (51%) had a favorable outcome (mRS of 0–3) at 3 months. The 7 patients who underwent secondary hematoma evacuation had a decrease in GCS score of at least two points prior to surgery; two (29%) had deceased at 3 months; and 5 (71%) had a good functional outcome (mRS 0–3).

Conclusions

While cerebellar ICH > 3 cm is often considered an indication for immediate hematoma evacuation, there may be a subgroup of patients in whom surgery can be safely deferred. Further data are needed to assess the optimal timing and indications of surgical treatment in these patients.
Effect of the catalyst in the BTX production by hydrocracking of light cycle oil
Authors: Laredo Georgina C. , García-Gutiérrez José L. , Pérez-Romo Patricia , Olmos-Cerda Eli H.
Published: March 2021

Catalysts to produce the important petrochemicals like benzene, toluene, and xylene (BTX) from refinery feedstocks, like light cycle oil (LCO) are reviewed here by covering published papers using model mixtures and real feeds. Model compounds experiments like tetralin and naphthalene derivatives provided a 53–55% total BTX yield. Higher yields were never attained due to the inevitable gas formation and other C9+-alkylbenzenes formed. For tetralin, the best catalysts are those conformed by Ni, CoMo, NiMo, or NiSn over zeolite H-Beta. For naphthalene derivatives, the best catalysts were those conformed by W and NiW over zeolite H-Beta silylated. Real feeds produced a total BTX yield of up to 35% at the best experimental conditions. Higher yields were never reached due to the presence of other types of hydrocarbons in the feed which can compete for the catalytic sites. The best catalysts were those conformed by Mo, CoMo, or NiMo over zeolite H-Beta. Some improvements were obtained by adding ZSM-5 to the support or in mixtures with other catalysts.
On mass and matter
Authors: Roberts Craig D.
Published: March 2021

The visible Universe is largely characterised by a single mass scale, namely, the proton mass,mp. Contemporary theory suggests thatmpemerges as a consequence of gluon self-interactions, which are a defining characteristic of quantum chromodynamics (QCD), the theory of strong interactions in the Standard Model. However, the proton is not elementary. Its mass appears as a corollary of other, more basic emergent phenomena latent in the QCD Lagrangian, e.g. generation of nuclear-size gluon and quark mass-scales, and a unique effective charge that may describe QCD interactions at all accessible momentum scales. These remarks are explained herein, and focusing on the distribution amplitudes and functions ofπandKmesons, promising paths for their empirical verification are elucidated. Connected therewith, in anticipation that production ofJ/ψ-mesons usingπandKbeams can provide access to the gluon distributions in these pseudo-Nambu-Goldstone modes, predictions for allπandKdistribution functions are provided at the scaleζ=mJ/ψ.
Structural and Functional Analyses of Hub MicroRNAs in An Integrated Gene Regulatory Network of Arabidopsis
Authors: Gao Zhaoxu , Li Jun , Li Li , Yang Yanzhi , Li Jian , Fu Chunxiang , Zhu Danmeng , He Hang , Cai Huaqing , Li Lei
Published: March 2021

MicroRNAs (miRNAs) are trans-acting small regulatory RNAs that work coordinately with transcription factors (TFs) to shape the repertoire of cellular mRNAs available for translation. Despite our growing knowledge of individual plant miRNAs, their global roles in gene regulatory networks remain mostly unassessed. Based on interactions obtained from public databases and curated from the literature, we reconstructed an integrated miRNA network in Arabidopsis that includes 66 core TFs, 318 miRNAs, and 1712 downstream genes. We found that miRNAs occupy distinct niches and enrich miRNA-containing feed-forward loops (FFLs), particularly those with miRNAs as intermediate nodes. Further analyses revealed that miRNA-containing FFLs coordinate TFs located in different hierarchical layers and that intertwined miRNA-containing FFLs are associated with party and date miRNA hubs. Using the date hub MIR858A as an example, we performed detailed molecular and genetic analyses of three interconnected miRNA-containing FFLs. These analyses revealed individual functions of the selected miRNA-containing FFLs and elucidated how the date hub miRNA fulfills multiple regulatory roles. Collectively, our findings highlight the prevalence and importance of miRNA-containing FFLs, and provide new insights into the design principles and control logics of miRNA regulatory networks governing gene expression programs in plants.
Chinese Glioma Genome Atlas (CGGA): A Comprehensive Resource with Functional Genomic Data from Chinese Glioma Patients
Authors: Zhao Zheng , Zhang Ke-Nan , Wang Qiangwei , Li Guanzhang , Zeng Fan , Zhang Ying , Wu Fan , Chai Ruichao , Wang Zheng , Zhang Chuanbao , Zhang Wei , Bao Zhaoshi , Jiang Tao
Published: March 2021

Gliomas are the most common and malignant intracranial tumors in adults. Recent studies have revealed the significance of functional genomics for glioma pathophysiological studies and treatments. However, access to comprehensive genomic data and analytical platforms is often limited. Here, we developed the Chinese Glioma Genome Atlas (CGGA), a user-friendly data portal for the storage and interactive exploration of cross-omics data, including nearly 2000 primary and recurrent glioma samples from Chinese cohort. Currently, open access is provided to whole-exome sequencing data (286 samples), mRNA sequencing (1018 samples) and microarray data (301 samples), DNA methylation microarray data (159 samples), and microRNA microarray data (198 samples), and to detailed clinical information (age, gender, chemoradiotherapy status, WHO grade, histological type, critical molecular pathological information, and survival data). In addition, we have developed several tools for users to analyze the mutation profiles, mRNA/microRNA expression, and DNA methylation profiles, and to perform survival and gene correlation analyses of specific glioma subtypes. This database removes the barriers for researchers, providing rapid and convenient access to high-quality functional genomic data resources for biological studies and clinical applications. CGGA is available at http://www.cgga.org.cn.
Robust Benchmark Structural Variant Calls of an Asian Using State-of-the-Art Long-Read Sequencing Technologies
Authors: Du Xiao , Li Lili , Liang Fan , Liu Sanyang , Zhang Wenxin , Sun Shuai , Sun Yuhui , Fan Fei , Wang Linying , Liang Xinming , Qiu Weijin , Fan Guangyi , Wang Ou , Yang Weifei , Zhang Jiezhong , Xiao Yuhui , Wang Yang , Wang Depeng , Qu Shoufang , Chen Fang , Huang Jie
Published: March 2021

The importance of structural variants (SVs) for human phenotypes and diseases is now recognized. Although a variety of SV detection platforms and strategies that vary in sensitivity and specificity have been developed, few benchmarking procedures are available to confidently assess their performances in biological and clinical research. To facilitate the validation and application of these SV detection approaches, we established an Asian reference material by characterizing the genome of an Epstein-Barr virus (EBV)-immortalized B lymphocyte line along with identified benchmark regions and high-confidence SV calls. We established a high-confidence SV callset with 8938 SVs by integrating four alignment-based SV callers, including 109× Pacific Biosciences (PacBio) continuous long reads (CLRs), 22× PacBio circular consensus sequencing (CCS) reads, 104× Oxford Nanopore Technologies (ONT) long reads, and 114× Bionano optical mapping platform, and one de novo assembly-based SV caller using CCS reads. A total of 544 randomly selected SVs were validated by PCR amplification and Sanger sequencing, demonstrating the robustness of our SV calls. Combining trio-binning-based haplotype assemblies, we established an SV benchmark for identifying false negatives and false positives by constructing the continuous high-confidence regions (CHCRs), which covered 1.46 gigabase pairs (Gb) and 6882 SVs supported by at least one diploid haplotype assembly. Establishing high-confidence SV calls for a benchmark sample that has been characterized by multiple technologies provides a valuable resource for investigating SVs in human biology, disease, and clinical research.
Concordance of antibiotic prescribing with the American Dental Association acute oral infection guidelines within Veterans’ Affairs (VA) dentistry
Authors: Carlsen Daniel B. , Durkin Michael J. , Gibson Gretchen , Jurasic M. Marianne , Patel Ursula , Poggensee Linda , Fitzpatrick Margaret A. , Echevarria Kelly , McGregor Jessina , Evans Charlesnika T. , Suda Katie J.
Published: March 2021

Objective:

United States dentists prescribe 10% of all outpatient antibiotics. Assessing appropriateness of antibiotic prescribing has been challenging due to a lack of guidelines for oral infections. In 2019, the American Dental Association (ADA) published clinical practice guidelines (CPG) on the management of acute oral infections. Our objective was to describe baseline national antibiotic prescribing for acute oral infections prior to the release of the ADA CPG and to identify patient-level variables associated with an antibiotic prescription.

Design:

Cross-sectional analysis.

Methods:

We performed an analysis of national VA data from January 1, 2017, to December 31, 2017. We identified cases of acute oral infections usingInternational Classification of Disease, Tenth Revision, Clinical Modification(ICD-10-CM) codes. Antibiotics prescribed by a dentist within ±7 days of a visit were included. Multivariable logistic regression identified patient-level variables associated with an antibiotic prescription.

Results:

Of the 470,039 VA dental visits with oral infections coded, 12% of patient visits with irreversible pulpitis, 17% with apical periodontitis, and 28% with acute apical abscess received antibiotics. Although the median days’ supply was 7, prolonged use of antibiotics was frequent (≥8 days, 42%–49%). Patients with high-risk cardiac conditions, prosthetic joints, and endodontic, implant, and oral and maxillofacial surgery dental procedures were more likely to receive antibiotics.

Conclusions:

Most treatments of irreversible pulpitis and apical periodontitis cases were concordant with new ADA guidelines. However, in cases where antibiotics were prescribed, prolonged antibiotic courses >7 days were frequent. These findings demonstrate opportunities for the new ADA guidelines to standardize and improve dental prescribing practices.
Inflammation in children with cystic fibrosis: contribution of bacterial production of long-chain fatty acids
Authors: Felton Erin , Burrell Aszia , Chaney Hollis , Sami Iman , Koumbourlis Anastassios C. , Freishtat Robert J. , Crandall Keith A. , Hahn Andrea
Published: March 2021

Background

Cystic fibrosis (CF) affects >70,000 people worldwide, yet the microbiologic trigger for pulmonary exacerbations (PExs) remains unknown. The objective of this study was to identify changes in bacterial metabolic pathways associated with clinical status.

Methods

Respiratory samples were collected at hospital admission for PEx, end of intravenous (IV) antibiotic treatment, and follow-up from 27 hospitalized children with CF. Bacterial DNA was extracted and shotgun DNA sequencing was performed. MetaPhlAn2 and HUMAnN2 were used to evaluate bacterial taxonomic and pathway relative abundance, while DESeq2 was used to evaluate differential abundance based on clinical status.

Results

The mean age of study participants was 10 years; 85% received combination IV antibiotic therapy (beta-lactam plus a second agent). Long-chain fatty acid (LCFA) biosynthesis pathways were upregulated in follow-up samples compared to end of treatment: gondoate (p = 0.012), oleate (p = 0.048), palmitoleate (p = 0.043), and pathways of fatty acid elongation (p = 0.012). Achromobacter xylosoxidans and Escherichia sp. were also more prevalent in follow-up compared to PEx (p < 0.001).

Conclusions

LCFAs may be associated with persistent infection of opportunistic pathogens. Future studies should more closely investigate the role of LCFA production by lung bacteria in the transition from baseline wellness to PEx in persons with CF.

Impact

Increased levels of LCFAs are found after IV antibiotic treatment in persons with CF.

LCFAs have previously been associated with increased lung inflammation in asthma.

This is the first report of LCFAs in the airway of persons with CF.

This research provides support that bacterial production of LCFAs may be a contributor to inflammation in persons with CF.

Future studies should evaluate LCFAs as predictors of future PExs.
Alterations in acylcarnitines, amines, and lipids inform about the mechanism of action of citalopram/escitalopram in major depression
Authors: MahmoudianDehkordi Siamak , Ahmed Ahmed T. , Bhattacharyya Sudeepa , Han Xianlin , Baillie Rebecca A. , Arnold Matthias , Skime Michelle K. , John-Williams Lisa St. , Moseley M. Arthur , Thompson J. Will , Louie Gregory , Riva-Posse Patricio , Craighead W. Edward , McDonald William , Krishnan Ranga , Rush A. John , Frye Mark A. , Dunlop Boadie W. , Weinshilboum Richard M. , Kaddurah-Daouk Rima ,   The Mood Disorders Precision Medicine Consortium (MDPMC), Kaddurah-Daouk Rima , Rush John , Tenenbaum Jessica , Moseley Arthur , Thompson Will , Louie Gregory , Blach Colette , Mahmoudiandehkhordi Siamak , Baillie Rebecca , Han Xianlin , Bhattacharyya Sudeepa , Frye Mark , Weinshilboum Richard , Ahmed Ahmed , Neavin Drew , Liu Duan , Skime Michelle , Rinaldo Piero , Fiehn Oliver , Brydges Christopher , Mayberg Helen , Choi Ki Sueng , Cha Jungho , Kastenmüller Gabi , Arnold Matthias , Binder Elisabeth , Knauer-Arloth Janine , Nevado-Holgado Alejo , Shi Liu , Dunlop Boadie , Craighead Ed , McDonald William , Posse Patricio Riva , Penninx Brenda , Milaneschi Yuri , Jansen Rick , Krishnan Ranga
Published: March 2021

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing a panel of 180 metabolites to gain insights into mechanisms of action and response to citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled into the Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) were profiled at baseline and after 8 weeks of treatment. After treatment, we saw increased levels of short-chain acylcarnitines and decreased levels of medium-chain and long-chain acylcarnitines, suggesting an SSRI effect on β-oxidation and mitochondrial function. Amines—including arginine, proline, and methionine sulfoxide—were upregulated while serotonin and sarcosine were downregulated, suggesting an SSRI effect on urea cycle, one-carbon metabolism, and serotonin uptake. Eighteen lipids within the phosphatidylcholine (PC aa and ae) classes were upregulated. Changes in several lipid and amine levels correlated with changes in 17-item Hamilton Rating Scale for Depression scores (HRSD17). Differences in metabolic profiles at baseline and post-treatment were noted between participants who remitted (HRSD17 ≤ 7) and those who gained no meaningful benefits (<30% reduction in HRSD17). Remitters exhibited (a) higher baseline levels of C3, C5, alpha-aminoadipic acid, sarcosine, and serotonin; and (b) higher week-8 levels of PC aa C34:1, PC aa C34:2, PC aa C36:2, and PC aa C36:4. These findings suggest that mitochondrial energetics—including acylcarnitine metabolism, transport, and its link to β-oxidation—and lipid membrane remodeling may play roles in SSRI treatment response.
Late-life depression and increased risk of dementia: a longitudinal cohort study
Authors: Ly M. , Karim H. T. , Becker J. T. , Lopez O. L. , Anderson S. J. , Aizenstein H. J. , Reynolds C. F. , Zmuda M. D. , Butters M. A.
Published: March 2021

Late-life depression (LLD) is associated with an increased risk of developing dementia; however, it is not known whether individuals with a history of LLD exhibit a more rapid rate of cognitive decline. We aimed to determine whether those with LLD experienced faster cognitive decline compared with never-depressed control (NDC) participants from the community and whether stratification of LLD into early-onset depression (EOD) and late-onset depression (LOD) subtypes revealed differing rates and domain-specific expression of cognitive decline. We conducted a prospective, longitudinal study where 185 participants with LLD (remitted) and 114 NDC were followed for 5 years on average. EOD was defined as having first lifetime depressive episode at <60years and LOD at ≥60years. Every year, participants underwent comprehensive neuropsychological assessment. Composite scores for each cognitive domain were calculated through averaging standardized scores across tests. LLD compared to NDC demonstrated significant baseline impairment but did not decline more rapidly. EOD were significantly impaired in attention/processing speed and global cognitive function at baseline but did not experience more rapid decline as compared to NDC. Those with LOD compared to both NDC and EOD performed worse in all domains at baseline and experienced more rapid decline in verbal skills and delayed memory ability. Our findings suggest that baseline impairment may lower the threshold for those with LLD to develop dementia. EOD and LOD may represent distinct phenotypes of cognitive impairment with differing neural substrates. LOD may represent a distinct phenotype with a more rapid decline in verbal skills and delayed memory.
Structural brain network topology underpinning ADHD and response to methylphenidate treatment
Authors: Griffiths Kristi R. , Braund Taylor A. , Kohn Michael R. , Clarke Simon , Williams Leanne M. , Korgaonkar Mayuresh S.
Published: March 2021

Behavioural disturbances in attention deficit hyperactivity disorder (ADHD) are thought to be due to dysfunction of spatially distributed, interconnected neural systems. While there is a fast-growing literature on functional dysconnectivity in ADHD, far less is known about the structural architecture underpinning these disturbances and how it may contribute to ADHD symptomology and treatment prognosis. We applied graph theoretical analyses on diffusion MRI tractography data to produce quantitative measures of global network organisation and local efficiency of network nodes. Support vector machines (SVMs) were used for comparison of multivariate graph measures of 37 children and adolescents with ADHD relative to 26 age and gender matched typically developing children (TDC). We also explored associations between graph measures and functionally-relevant outcomes such as symptom severity and prediction of methylphenidate (MPH) treatment response. We found that multivariate patterns of reduced local efficiency, predominantly in subcortical regions (SC), were able to distinguish between ADHD and TDC groups with 76% accuracy. For treatment prognosis, higher global efficiency, higher local efficiency of the right supramarginal gyrus and multivariate patterns of increased local efficiency across multiple networks at baseline also predicted greater symptom reduction after 6 weeks of MPH treatment. Our findings demonstrate that graph measures of structural topology provide valuable diagnostic and prognostic markers of ADHD, which may aid in mechanistic understanding of this complex disorder.
A novel art of continuous noninvasive blood pressure measurement
Authors: Fortin Jürgen , Rogge Dorothea E. , Fellner Christian , Flotzinger Doris , Grond Julian , Lerche Katja , Saugel Bernd
Published: March 2021

Wearable sensors to continuously measure blood pressure and derived cardiovascular variables have the potential to revolutionize patient monitoring. Current wearable methods analyzing time components (e.g., pulse transit time) still lack clinical accuracy, whereas existing technologies for direct blood pressure measurement are too bulky. Here we present an innovative art of continuous noninvasive hemodynamic monitoring (CNAP2GO). It directly measures blood pressure by using a volume control technique and could be used for small wearable sensors integrated in a finger-ring. As a software prototype, CNAP2GO showed excellent blood pressure measurement performance in comparison with invasive reference measurements in 46 patients having surgery. The resulting pulsatile blood pressure signal carries information to derive cardiac output and other hemodynamic variables. We show that CNAP2GO can self-calibrate and be miniaturized for wearable approaches. CNAP2GO potentially constitutes the breakthrough for wearable sensors for blood pressure and flow monitoring in both ambulatory and in-hospital clinical settings.
Observation of an electronic order along [110] direction in FeSe
Authors: Bu Kunliang , Zhang Wenhao , Fei Ying , Zheng Yuan , Ai Fangzhou , Wu Zongxiu , Wang Qisi , Wo Hongliang , Zhao Jun , Yin Yi
Published: March 2021

Multiple ordered states have been observed in unconventional superconductors. Here, we apply scanning tunneling microscopy to probe the intrinsic ordered states in FeSe, the structurally simplest iron-based superconductor. Besides the well-known nematic order along [100] direction, we observe a checkerboard charge order in the iron lattice, which we name a [110] electronic order in FeSe. The [110] electronic order is robust at 77 K, accompanied with the rather weak [100] nematic order. At 4.5 K, The [100] nematic order is enhanced, while the [110] electronic order forms domains with reduced correlation length. In addition, the collective [110] order is gaped around [−40, 40] meV at 4.5 K. The observation of this exotic electronic order may shed new light on the origin of the ordered states in FeSe.
Programmable C:G to G:C genome editing with CRISPR-Cas9-directed base excision repair proteins
Authors: Chen Liwei , Park Jung Eun , Paa Peter , Rajakumar Priscilla D. , Prekop Hong-Ting , Chew Yi Ting , Manivannan Swathi N. , Chew Wei Leong
Published: March 2021

Many genetic diseases are caused by single-nucleotide polymorphisms. Base editors can correct these mutations at single-nucleotide resolution, but until recently, only allowed for transition edits, addressing four out of twelve possible DNA base substitutions. Here, we develop a class of C:G to G:C Base Editors to create single-base genomic transversions in human cells. Our C:G to G:C Base Editors consist of a nickase-Cas9 fused to a cytidine deaminase and base excision repair proteins. Characterization of >30 base editor candidates reveal that they predominantly perform C:G to G:C editing (up to 90% purity), with rAPOBEC-nCas9-rXRCC1 being the most efficient (mean 15.4% and up to 37% without selection). C:G to G:C Base Editors target cytidine in WCW, ACC or GCT sequence contexts and within a precise three-nucleotide window of the target protospacer. We further target genes linked to dyslipidemia, hypertrophic cardiomyopathy, and deafness, showing the therapeutic potential of these base editors in interrogating and correcting human genetic diseases.
Structures of mouse and human GITR–GITRL complexes reveal unique TNF superfamily interactions
Authors: Wang Feng , Chau Bryant , West Sean M. , Kimberlin Christopher R. , Cao Fei , Schwarz Flavio , Aguilar Barbara , Han Minhua , Morishige Winse , Bee Christine , Dollinger Gavin , Rajpal Arvind , Strop Pavel
Published: March 2021

Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and GITR ligand (GITRL) are members of the tumor necrosis superfamily that play a role in immune cell signaling, activation, and survival. GITR is a therapeutic target for directly activating effector CD4 and CD8 T cells, or depleting GITR-expressing regulatory T cells (Tregs), thereby promoting anti-tumor immune responses. GITR activation through its native ligand is important for understanding immune signaling, but GITR structure has not been reported. Here we present structures of human and mouse GITR receptors bound to their cognate ligands. Both species share a receptor–ligand interface and receptor–receptor interface; the unique C-terminal receptor–receptor enables higher order structures on the membrane. Human GITR–GITRL has potential to form a hexameric network of membrane complexes, while murine GITR–GITRL complex forms a linear chain due to dimeric interactions. Mutations at the receptor–receptor interface in human GITR reduce cell signaling with in vitro ligand binding assays and minimize higher order membrane structures when bound by fluorescently labeled ligand in cell imaging experiments.
General molten-salt route to three-dimensional porous transition metal nitrides as sensitive and stable Raman substrates
Authors: Guan Haomin , Li Wentao , Han Jing , Yi Wencai , Bai Hua , Kong Qinghong , Xi Guangcheng
Published: March 2021

Transition metal nitrides have been widely studied due to their high electrical conductivity and excellent chemical stability. However, their preparation traditionally requires harsh conditions because of the ultrahigh activation energy barrier they need to cross in nucleation. Herein, we report three-dimensional porous VN, MoN, WN, and TiN with high surface area and porosity that are prepared by a general and mild molten-salt route. Trace water is found to be a key factor for the formation of these porous transition metal nitrides. The porous transition metal nitrides show hydrophobic surface and can adsorb a series of organic compounds with high capacity. Among them, the porous VN shows strong surface plasmon resonance, high conductivity, and a remarkable photothermal conversion efficiency. As a new type of corrosion- and radiation-resistant surface-enhanced Raman scattering substrate, the porous VN exhibits an ultrasensitive detection limit of 10−11 M for polychlorophenol.
Author Correction: High gain, wide-angle QCTO-enabled modified Luneburg lens antenna with broadband anti-reflective layer
Authors: Biswas Soumitra , Mirotznik Mark
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Modeling of CO2-LPG WAG with asphaltene deposition to predict coupled enhanced oil recovery and storage performance
Authors: Cho Jinhyung , Min Baehyun , Jeong Moon Sik , Lee Young Woo , Lee Kun Sang
Published: March 2021

Combined carbon capture and storage and CO2-enhanced oil recovery (CCS-EOR) can reconcile the demands of business with the need to mitigate the effects of climate change. To improve the performance of CCS-EOR, liquefied petroleum gas (LPG) can be co-injected with CO2, leading to a reduction in the minimum miscibility pressure. However, gas injection can cause asphaltene problems, which undermines EOR and CCS performances simultaneously. Here, we systematically examine the mechanisms of asphaltene deposition using compositional simulations during CO2-LPG–comprehensive water–alternating-gas (WAG) injection. The LPG accelerates asphaltene deposition, reducing gas mobility, and increases the performance of residual trapping by 9.2% compared with CO2 WAG. In contrast, solubility trapping performance declines by only 3.7% because of the greater reservoir pressure caused by the increased formation damage. Adding LPG enhances oil recovery by 11% and improves total CCS performance by 9.1% compared with CO2 WAG. Based on reservoir simulations performed with different LPG concentrations and WAG ratios, we confirmed that the performance improvement of CCS-EOR associated with increasing LPG and water injection reaches a plateau. An economic evaluation based on the price of LPG should be carried out to ensure practical success.