bluuebunny/crossref_metadata_2025 huggingface dataset:
Jenang: Food Production System Based on Myths in Java, Indonesia
Authors: Wibowo A
Published: August 2021

Traditional foods made from local ingredients remain in the limelight, based on superiority or uniqueness. This study therefore describes the preparation of Jenang as a traditional food, based on mythical concept, thus, becoming Indonesia’s favorite food. The study was conducted in a natural environment (natural setting), using a qualitative method, with an ethnographic approach. In ethnographic research, researchers visit a place where people or groups ‘being studied’ live to ‘experience together’ the daily routines and habits, and consequently, understand social life and culture from the people’s point of view. Researchers’ collect data through the senses of sight, hearing, and taste, as well as interviews and observations, in order to formulate problems and discover solutions. According to the results, Jenang is indeed Indonesia’s favorite food because myths play an important role in building the production systems. These roles include, source of inspiration, communication strategy in maintaining Jenang authenticity and quality, and a strategy in increasing popularity. This is affiliated with philosophical myths and symbols believed by the Javanese, as a communication strategy for building vertical relationships with the Creator, and for building horizontal relationships with fellow creatures. These vertical relations are in the sense of gratitude to God Almighty, while the horizontal counterpart are a symbol of unity among fellow humans, to foster a spirit of togetherness in the Javanese society, and as an apology to nature, for negative actions.
Managerial implication of cassava farming in Lampung Province Indonesia
Authors: Zakaria W A , Sayekti W D , Indah L S M , Seta A P
Published: August 2021

The problem of low productivity, quality, and price of cassava keep occurring over the years, from 2016 to 2019. This situation affected farmers’ income, both directly and indirectly, later causing reduction of welfare, especially of those in Central Lampung Regency, being the largest cassava production area in Indonesia. This study aimed to determine the level of optimal solutions in cassava farming, in Central Lampung Regency, while also ascertaining the managerial implications on farmers. Furthermore, the study was conducted between the period of October-December 2019, applying a survey method on 78 cassava farmers in Central Lampung Regency. The optimal planning method used was an analytical technique with linear programming model, and qualitative descriptive analysis. The managerial implications of optimizing cassava cultivation were meant to increase the performances of farming and supporting subsystems, based on the use of seeds, fertilizers (urea, NPK, TSP, KCL, and organic fertilizer), labour, land intensification, and management in other substructures.
The strategy of Increasing Customer Satisfaction of Coffee Shop in Yogyakarta through GAP Analysis
Authors: Riswara E P , Wagiman  , Purwadi D
Published: August 2021

Yogyakarta as a city of tourism and education mostly has young people as potential coffee customers. Furthermore, service needs, which lead to customer satisfaction are determined through the diversity of young people and coffee shops. Meanwhile, customer satisfaction is analytically based on five dimensions of service quality, which are important for improving and innovating strategies to increase satisfaction. Therefore, this study aims to describe the quality of coffee shop services, measure the gap between their perception and expectation, and formulate a business strategy to increase customer satisfaction. To achieve this, the survey approach was adopted, which relies on secondary and primary data from the dissemination of questionnaires to different coffee shops. Furthermore, five-dimensional service quality was elaborated to achieve an improved strategy of customer satisfaction.
Comparative study of C–V-based extraction methods of interface state density for a low-temperature polysilicon thin film
Authors: Lee Woohui , Oh Joohee , Chu Jae Hwan , Choi Sanggun , Kang Taewook , Chu Hyeyong , Kim Hyoungsub
Published: August 2021

To extract comprehensive and accurate interface state density (D
it) distribution for a low-temperature polysilicon (LTPS) thin film, three well-established methods based on capacitance–voltage (C–V) measurements were compared: high–low frequency capacitance, conductance, and quasi-static (QS) capacitance methods. Because of the strong frequency-dependent response of grain boundary traps within the LTPS, C–V measurements are necessary on p- as well as n-type LTPS films, as they provide D
it distribution across the entire LTPS band gap. The QS capacitance method, which uses an optimal high-frequency C–V curve with a minimal grain boundary trap response, provided the best and most comprehensive estimate of D
it distribution across the LTPS band gap, even at room temperature (25 °C). Although the narrow extraction ranges of D
it were extended toward the mid-gap region by increasing the measurement temperature in both high–low frequency capacitance and conductance methods, the responses of the grain boundary traps still overestimated the D
it values near the band edges.
Remarks on the decay of Fourier coefficients to solutions of Navier-Stokes system
Authors: Deng Wen , Paicu Marius , Zhang Ping
Published: August 2021

We first investigate the large time decay of the Fourier coefficients to the global mild solution of Navier-Stokes system with periodic boundary condition and with small enough initial data. In particular, this result ensures the fast decay of Fourier coefficients to any global solution
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="u element-of upper C left-parenthesis left-bracket 0 comma normal infinity left-bracket semicolon ModifyingAbove upper H With dot Superscript one half Baseline left-parenthesis double-struck upper T cubed right-parenthesis right-parenthesis">

u
∈
C
(
[
0
,
∞
[
;

H
˙

1
2

(

T

3

)
)

u\in C([0,\infty [;\dot H^{\frac 12}({\mathbb T}^3))

of Navier-Stokes system. Then we extend this result to Navier-Stokes system with an additional low frequency damping term in the whole space. Finally, we prove that the radius of analyticity

R
(
t
)

R(t)

to this modified system with small initial data in

H
˙

1
2

(

R

3

)

\dot {H}^{\frac 12}(\mathbb {R}^3)

is bounded from below by a positive constant times

t
,

t,

which makes sharp contrast with the corresponding result for the classical Navier-Stokes system that 

R
(
t
)

t

−

1
2

R(t)t^{-\frac 12}

is bounded from below by a positive constant.
𝑆𝑝-equivariant modules over polynomial rings in infinitely many variables
Authors: Sam Steven , Snowden Andrew
Published: August 2021

We study the category of

S
p

\mathbf {Sp}

-equivariant modules over the infinite variable polynomial ring, where

S
p

\mathbf {Sp}

denotes the infinite symplectic group. We establish a number of results about this category: for instance, we show that every finitely generated module

M
M

fits into an exact triangle

T
→
M
→
F
→

T \to M \to F \to

where

T
T

is a finite length complex of torsion modules and

F
F

is a finite length complex of “free” modules; we determine the Grothendieck group; and we (partially) determine the structure of injective modules. We apply these results to show that the twisted commutative algebras

Sym
⁡
(

C

∞

⊕

⋀
2

C

∞

)

\operatorname {Sym}(\mathbf {C}^{\infty } \oplus \bigwedge ^2{\mathbf {C}^{\infty }})

and

Sym
⁡
(

C

∞

⊕

Sym
2

⁡

C

∞

)

\operatorname {Sym}(\mathbf {C}^{\infty } \oplus \operatorname {Sym}^2{\mathbf {C}^{\infty }})

are noetherian, which are the strongest results to date of this kind. We also show that the free 2-step nilpotent twisted Lie algebra and Lie superalgebra are noetherian.
Infinite 𝑝-adic random matrices and ergodic decomposition of 𝑝-adic Hua measures
Authors: Assiotis Theodoros
Published: August 2021

Neretin in [Izv. Ross. Akad. Nauk Ser. Mat. 77 (2013), pp. 95–108] constructed an analogue of the Hua measures on the infinitepp-adic matricesMat(N,Qp)\mathrm {Mat}\left (\mathbb {N},\mathbb {Q}_p\right ). Bufetov and Qiu in [Compos. Math. 153 (2017), pp. 2482–2533] classified the ergodic measures onMat(N,Qp)\mathrm {Mat}\left (\mathbb {N},\mathbb {Q}_p\right )that are invariant under the natural action of<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="normal upper G normal upper L left-parenthesis normal infinity comma double-struck upper Z Subscript p Baseline right-parenthesis times normal upper G normal upper L left-parenthesis normal infinity comma double-struck upper Z Subscript p Baseline right-parenthesis">GL(∞,Zp)×GL(∞,Zp)\mathrm {GL}(\infty ,\mathbb {Z}_p)\times \mathrm {GL}(\infty ,\mathbb {Z}_p). In this paper we solve the problem of ergodic decomposition for thepp-adic Hua measures introduced by Neretin. We prove that the probability measure governing the ergodic decomposition has an explicit expression which identifies it with a Hall-Littlewood measure on partitions. Our arguments involve certain Markov chains.
Sequestration of the exocytic SNARE Psy1 into multiprotein nodes reinforces polarized morphogenesis in fission yeast
Authors: Miller Kristi E. , Magliozzi Joseph O. , Picard Noelle A. , Moseley James B.
Published: August 2021

Cell shape requires mechanisms that restrict polarized growth to defined sites. Here, we show that the fission yeast exocytic t-SNARE is sequestered into megadalton-sized nodes along cell sides, where growth is inhibited. Loss of nodes leads to ectopic exocytosis and defects in cell shape.
Yeast Nst1 is a novel component of P-bodies and is a specific suppressor of proteasome base assembly defects
Authors: Cheng Chin Leng , Wong Michael K. , Hochstrasser Mark
Published: August 2021

We identified negative salt tolerance 1 (Nst1) as a dosage suppressor of the temperature sensitivity and proteasome assembly defects in multiple base mutants. Both endogenous and overexpressed Nst1 could localize to processing bodies. Nst1 overexpression inhibited global protein translation that in turn suppressed aggregation and proteasome assembly defects in base assembly mutants.
The Role of Micronutrients in the Pathogenesis of Alcohol-Related Liver Disease
Authors: Nicoll Ruairidh , Gerasimidis Konstantinos , Forrest Ewan
Published: August 2021

Aims

Chronic alcohol consumption may result in liver injury and chronic liver disease, but other factors are likely to influence disease progression. Malnutrition, specifically micronutrient deficiency, is frequently associated with both alcohol use disorder and chronic liver disease. We hypothesize that micronutrient deficiencies may affect the progression of liver disease in this population.

Methods

Systematic integrative review of the medical literature; electronic search of MEDLINE 1950–2021; studies investigating role of any micronutrient in the acceleration of alcohol-related liver injury in humans or animals. Studies which specifically related to alcoholic hepatitis were excluded. Outcomes were extracted and recorded in tabulated form and discussed narratively.

Results

We identified 46 studies investigating the role of micronutrient deficiencies in the pathogenesis of alcohol-related liver disease. Specific micronutrients which were identified included folic acid or related B vitamins (n = 9 studies), Vitamin D (n = 9 studies), magnesium (n = 8 studies), zinc (n = 8 studies) and selenium (n = 12 including one systematic review). Observational evidence suggests a potential role of magnesium deficiency in accelerating alcohol-related liver injury with weak or negative evidence for other micronutrients.

Conclusions

Magnesium deficiency may increase the risk of alcohol-related liver injury and adverse liver outcomes. However, currently, there is insufficient evidence to support magnesium supplementation except for clinically relevant magnesium deficiency. Long-term prospective cohort studies assessing the impact of micronutrients on liver disease progression in patients with alcohol use disorder are lacking and may help determine whether there is a causal role for micronutrient deficiencies in alcohol-related liver injury.
Bioavailability comparison between a compound comprising hesperetin-7-glucoside with β-cyclodextrin and a mixture of hesperidin and dextrin in healthy adult human males
Authors: Moriwaki Masamitsu , Kito Kento , Nakagawa Ryo , Kapoor Mahendra P , Matsumiya Yoshiki , Fukuhara Tomohisa , Kamiya Uguri
Published: August 2021

The pharmacokinetics of compounds comprising hesperetin-7-glucoside with β-cyclodextrin and physically mixed hesperidin/dextrin was compared in 8 healthy adult male subjects in a nonrandomized, double-blind, cross-over, controlled study. For 0-24 h, the area under the curve of the total plasma hesperetin concentration after hesperetin-7-glucoside with β-cyclodextrin consumption was >100-fold higher than that after hesperidin/dextrin consumption.
Improved protein contact prediction using dimensional hybrid residual networks and singularity enhanced loss function
Authors: Si Yunda , Yan Chengfei
Published: August 2021

Deep residual learning has shown great success in protein contact prediction. In this study, a new deep residual learning-based protein contact prediction model was developed. Comparing with previous models, a new type of residual block hybridizing 1D and 2D convolutions was designed to increase the effective receptive field of the residual network, and a new loss function emphasizing the easily misclassified residue pairs was proposed to enhance the model training. The developed protein contact prediction model referred to as DRN-1D2D was first evaluated on 105 CASP11 targets, 76 CAMEO hard targets and 398 membrane proteins together with two in house-developed reference models based on either the standard 2D residual block or the traditional BCE loss function, from which we confirmed that both the dimensional hybrid residual block and the singularity enhanced loss function can be employed to improve the model performance for protein contact prediction. DRN-1D2D was further evaluated on 39 CASP13 and CASP14 free modeling targets together with the two reference models and six state-of-the-art protein contact prediction models including DeepCov, DeepCon, DeepConPred2, SPOT-Contact, RaptorX-Contact and TripleRes. The result shows that DRN-1D2D consistently achieved the best performance among all these models.
Maximization of non-idle enzymes improves the coverage of the estimated maximal in vivo enzyme catalytic rates in Escherichia coli
Authors: Xu Rudan , Razaghi-Moghadam Zahra , Nikoloski Zoran
Published: August 2021

Motivation

Constraint-based modeling approaches allow the estimation of maximal in vivo enzyme catalytic rates that can serve as proxies for enzyme turnover numbers. Yet, genome-scale flux profiling remains a challenge in deploying these approaches to catalogue proxies for enzyme catalytic rates across organisms.

Results

Here, we formulate a constraint-based approach, termed NIDLE-flux, to estimate fluxes at a genome-scale level by using the principle of efficient usage of expressed enzymes. Using proteomics data from Escherichia coli, we show that the fluxes estimated by NIDLE-flux and the existing approaches are in excellent qualitative agreement (Pearson correlation > 0.9). We also find that the maximal in vivo catalytic rates estimated by NIDLE-flux exhibits a Pearson correlation of 0.74 with in vitro enzyme turnover numbers. However, NIDLE-flux results in a 1.4-fold increase in the size of the estimated maximal in vivo catalytic rates in comparison to the contenders. Integration of the maximum in vivo catalytic rates with publically available proteomics and metabolomics data provide a better match to fluxes estimated by NIDLE-flux. Therefore, NIDLE-flux facilitates more effective usage of proteomics data to estimate proxies for kcatomes.

Availability and implementation

https://github.com/Rudan-X/NIDLE-flux-code.

Supplementary information

Supplementary data are available at Bioinformatics online.
The Immigration–Crime Relationship: Evidence Across and Within Vancouver Census Tracts 2003–16
Authors: Ha Olivia K , Andresen Martin A
Published: August 2021

We evaluate the relationships between immigration and crime at the census tract level. Using multiple measures of immigration considering nuances of the immigrant population and a statistical technique allowing for the identification of long- and short-run effects, we provide further evidence of the negative relationship between immigration and crime. However, we note that these relationships are not monolithic. Similar to the original work on social disorganization theory, we find evidence for census tracts with increases in immigration have increased levels of crime because of restricted access to resources and initial settlement in high crime areas. However, over time, our results suggest that greater integration and the development of social capital (longer term immigration) is negatively associated with crime.
Imaging predictors of successful surgical treatment of hemifacial spasm
Authors: Hughes Marion A , Traylor Katie S , Branstetter IV Barton F , Eubanks Komal P , Chang Yue-Fang , Sekula Jr Raymond F
Published: August 2021

Identify preoperative imaging findings in hemifacial spasm patients that predict the post-surgical success following microvascular decompression. This is a retrospective study of patients who were diagnosed with hemifacial spasm, had a dedicated cranial nerve MRI, and underwent microvascular decompression for hemifacial spasm. Bilateral facial nerves were interrogated for neurovascular compression. If neurovascular compression was identified, we recorded whether the offending vessel was an artery, a vein or both. The location of the neurovascular compression (proximal nerve versus distal nerve) was noted. The severity of the neurovascular compression was categorized as contact versus deformity of the nerve. Patients were contacted to determine their post-operative spasm status. The relationships between imaging findings and post-surgical outcome were assessed by Chi-square tests, and odds ratios were calculated to quantify the degree of association. The study included 212 patients. Upon follow up, 192 patients were spasm free (90.57%). Imaging findings on the symptomatic side were as follows: arterial neurovascular compression was seen in 207 patients (97.64%), venous only neurovascular compression in two patients (0.94%), and no neurovascular compression in three patients (1.42%). Arterial neurovascular compression along the proximal, susceptible segment of the nerve was observed in 202 patients (95.28%); deformity was observed more commonly than contact alone. Arterial neurovascular compression along the distal segment only of the nerve was observed in five patients (2.36%). In patients with arterial neurovascular compression of the proximal and distal portions of the nerve, 93.07% and 60.0% of patients were spasm-free respectively. If venous neurovascular compression only was observed on imaging, 0% of patients were spasm-free. Patients with arterial neurovascular compression of the susceptible segment are much more likely to be spasm free than patients without this imaging finding, [odds ratio 20.14 (CI 5.08, 79.81), P-value <0.0001]. When comparing the two groups of arterial neurovascular compression (deformity versus contact), no statistically significant difference in outcomes was observed. In patients with hemifacial spasm undergoing microvascular decompression, imaging findings do predict surgical outcome. Patients with arterial neurovascular compression of the proximal, susceptible portion of the nerve are much more likely to be spasm free after surgery than those without this imaging finding. The imaging findings inform the risk benefit analysis and discussion with patients before they undergo microvascular decompression for hemifacial spasm.
Reconciling Egg- and Antigen-Based Estimates of Schistosoma mansoni Clearance and Reinfection: A Modeling Study
Authors: Clark Jessica , Moses Arinaitwe , Nankasi Andrina , Faust Christina L , Moses Adriko , Ajambo Diana , Besigye Fred , Atuhaire Aaron , Wamboko Aidah , Carruthers Lauren V , Francoeur Rachel , Tukahebwa Edridah M , Prada Joaquin M , Lamberton Poppy H L
Published: August 2021

Background

Despite decades of interventions, 240 million people have schistosomiasis. Infections cannot be directly observed, and egg-based Kato-Katz thick smears lack sensitivity, affected treatment efficacy and reinfection rate estimates. The point-of-care circulating cathodic antigen (referred to from here as POC-CCA+) test is advocated as an improvement on the Kato-Katz method, but improved estimates are limited by ambiguities in the interpretation of trace results.

Method

We collected repeated Kato-Katz egg counts from 210 school-aged children and scored POC-CCA tests according to the manufacturer’s guidelines (referred to from here as POC-CCA+) and the externally developed G score. We used hidden Markov models parameterized with Kato-Katz; Kato-Katz and POC-CCA+; and Kato-Katz and G-Scores, inferring latent clearance and reinfection probabilities at four timepoints over six-months through a more formal statistical reconciliation of these diagnostics than previously conducted. Our approach required minimal but robust assumptions regarding trace interpretations.

Results

Antigen-based models estimated higher infection prevalence across all timepoints compared with the Kato-Katz model, corresponding to lower clearance and higher reinfection estimates. Specifically, pre-treatment prevalence estimates were 85% (Kato-Katz; 95% CI: 79%–92%), 99% (POC-CCA+; 97%–100%) and 98% (G-Score; 95%–100%). Post-treatment, 93% (Kato-Katz; 88%–96%), 72% (POC-CCA+; 64%–79%) and 65% (G-Score; 57%–73%) of those infected were estimated to clear infection. Of those who cleared infection, 35% (Kato-Katz; 27%–42%), 51% (POC-CCA+; 41%–62%) and 44% (G-Score; 33%–55%) were estimated to have been reinfected by 9-weeks.

Conclusions

Treatment impact was shorter-lived than Kato-Katz–based estimates alone suggested, with lower clearance and rapid reinfection. At 3 weeks after treatment, longer-term clearance dynamics are captured. At 9 weeks after treatment, reinfection was captured, but failed clearance could not be distinguished from rapid reinfection. Therefore, frequent sampling is required to understand these important epidemiological dynamics.
Public-Key Authenticated Encryption with Keyword Search: A Generic Construction and Its Quantum-Resistant Instantiation
Authors: Liu Zi-Yuan , Tseng Yi-Fan , Tso Raylin , Mambo Masahiro , Chen Yu-Chi
Published: August 2021

The industrial Internet of Things (IIoT) integrates sensors, instruments, equipment and industrial applications, enabling traditional industries to automate and intelligently process data. To reduce the cost and demand of required service equipment, IIoT relies on cloud computing to further process and store data. Public-key encryption with keyword search (PEKS) plays an important role, due to its search functionality, to ensure the privacy and confidentiality of the outsourced data and the maintenance of flexibility in the use of the data. Recently, Huang and Li proposed the ‘public-key authenticated encryption with keyword search’ (PAEKS) to avoid the insider keyword guessing attacks (IKGAs) in the previous PEKS schemes. However, all current PAEKS schemes are based on the discrete logarithm assumption and are therefore vulnerable to quantum attacks. In this study, we first introduce a generic PAEKS construction, with the assistance of a trusted authority, that enjoys the security against IKGA in the standard model, if all building blocks are secure under standard model. Based on the framework, we further propose a novel instantiation of quantum-resistant PAEKS that is based on NTRU assumption under random oracle. Compared with its state-of-the-art counterparts, the experiment result indicates that our instantiation is more efficient and secure.
MicroRNA-27b-3p down-regulates FGF1 and aggravates pathological cardiac remodelling
Authors: Li Guoqi , Shao Yihui , Guo Hong Chang , Zhi Ying , Qiao Bokang , Ma Ke , Du Jie , Lai Yong Qiang , Li Yulin
Published: August 2021

Aims

The heart undergoes pathological remodelling under increased stress and neuronal imbalance. MicroRNAs (miRNAs) are involved in post-transcriptional regulation of genes in cardiac physiology and pathology. However, the mechanisms underlying miRNA-mediated regulation of pathological cardiac remodelling remain to be studied. This study aimed to explore the function of endogenous microRNA-27b-3p (miR-27b-3p) in pathological cardiac remodelling.

Methods and results

miR-27b-3p expression was elevated in the heart of a transverse aortic constriction (TAC)-induced cardiac hypertrophy mouse model. miR-27b-knockout mice showed significantly attenuated cardiac hypertrophy, fibrosis, and inflammation induced by two independent pathological cardiac hypertrophy models, TAC and Angiotensin II (Ang II) perfusion. Transcriptome sequencing analysis revealed that miR-27b deletion significantly down-regulated TAC-induced cardiac hypertrophy, fibrosis, and inflammatory genes. We identified fibroblast growth factor 1 (FGF1) as a miR-27b-3p target gene in the heart which was up-regulated in miR-27b-null mice. We found that both recombinant FGF1 (rFGF1) and inhibition of miR-27b-3p enhanced mitochondrial oxidative phosphorylation (OXPHOS) and inhibited cardiomyocyte hypertrophy. Importantly, rFGF1 administration inhibited cardiac hypertrophy and fibrosis in TAC- or Ang II-induced models and enhanced OXPHOS by activating PGC1α/β.

Conclusions

Our study demonstrated that miR-27b-3p induces pathological cardiac remodelling and suggests that inhibition of endogenous miR-27b-3p or administration of FGF1 might have the potential to suppress cardiac remodelling in a clinical setting.
Using multimarker screening to identify biomarkers associated with cardiovascular death in patients with atrial fibrillation
Authors: Pol Tymon , Hijazi Ziad , Lindbäck Johan , Oldgren Jonas , Alexander John H , Connolly Stuart J , Eikelboom John W , Ezekowitz Michael D , Granger Christopher B , Lopes Renato D , Yusuf Salim , Siegbahn Agneta , Wallentin Lars
Published: August 2021

Aims

Atrial fibrillation (AF) is associated with higher mortality. Biomarkers may improve the understanding of key pathophysiologic processes in AF that lead to death. Using a new multiplex analytic technique, we explored the association between 268 biomarkers and cardiovascular (CV) death in anticoagulated patients with AF.

Methods and results

A case–cohort design with 1.8- to 1.9-year follow-up. The identification cohort included 517 cases and 4057 randomly selected patients from ARISTOTLE. The validation cohort included 277 cases and 1042 randomly selected controls from RE-LY. Plasma collected at randomization was analysed with conventional immunoassays and the OLINK proximity extension assay panels: CVDII, CVDIII, and Inflammation. Association between biomarkers and CV death was evaluated using Random Survival Forest, Boruta, and adjusted Cox-regression analyses. The biomarkers most strongly and consistently associated with CV death were as follows (hazard ratio for inter-quartile comparison [95% CI]): N-terminal pro-B-type natriuretic peptide [NT-proBNP; 1.63 (1.37–1.93)], cardiac troponin T [cTnT-hs; 1.60 (1.35–1.88)], interleukin-6 [IL-6; 1.29 (1.13–1.47)], growth differentiation factor-15 [GDF-15; 1.30 (1.10–1.53)], fibroblast growth factor 23 [FGF-23; 1.21 (1.10–1.33)], urokinase receptor [uPAR; 1.38 (1.16–1.64)], trefoil factor 3 [TFF3; 1.27 (1.10–1.46)], tumour necrosis factor receptor 1 [TNFR1; 1.21 (1.01–1.45)], TNF-related apoptosis-inducing ligand receptor 2 [TRAILR2; 1.18 (1.04–1.34)], and cathepsin L1 [CTSL1; 1.22 (1.07–1.39)].

Conclusion

In this comprehensive screening of 268 biomarkers in anticoagulated patients with AF, the underlying mechanisms most strongly associated with CV death were cardiorenal dysfunction (NT-proBNP, cTnT-hs, CTSL1, TFF3), oxidative stress (GDF-15), inflammation (IL-6, GDF-15), calcium balance, vascular and renal dysfunction (FGF-23), fibrinolysis (suPAR), and apoptosis (TNFR1, TRAILR2). These findings provide novel insights into pathophysiologic aspects associated with CV death in AF.

ClinicalTrials.gov identifier

NCT00412984 and NCT00262600.
Case report: acute myocarditis following the second dose of mRNA-1273 SARS-CoV-2 vaccine
Authors: Tailor Prashant D , Feighery Aoife M , El-Sabawi Bassim , Prasad Abhiram
Published: August 2021

Background

The SARS-CoV-2 pandemic has led to the development of the first mRNA vaccines used in humans. The vaccines are well tolerated, safe, and highly efficacious; however, post-marketing surveillance is revealing potential rare adverse effects. We report a case of symptomatic acute myocarditis following administration of the second dose of mRNA-1273 SARS-CoV-2 vaccine.

Case summary

A 44-year-old man presented with chest pain and ST-segment elevation 4 days after receiving the second dose of mRNA-1273 SARS-CoV-2 Vaccine. Emergent coronary angiogram showed minimal coronary artery disease. Cardiac magnetic resonance imaging confirmed acute myocarditis. Diagnosis of vaccine-associated myocarditis was made given the temporal relationship and supportive treatment initiated. Follow-up at 1 month confirmed complete symptomatic recovery and echocardiogram demonstrated normalization of cardiac function.

Discussion

Acute myocarditis should be considered in patients who present with chest pain or dyspnoea within days of receiving mRNA-1273 SARS-CoV-2 vaccination, especially after the second dose. This may be managed successfully with supportive therapies with complete recovery of cardiac function and symptoms. Further research is warranted to determine the mechanisms by which mRNA vaccines may cause myocarditis and for potential long-term cardiovascular injury.
Types of myocardial injury and mid-term outcomes in patients with COVID-19
Authors: Kini Annapoorna , Cao Davide , Nardin Matteo , Sartori Samantha , Zhang Zhongjie , Pivato Carlo Andrea , Chiarito Mauro , Nicolas Johny , Vengrenyuk Yuliya , Krishnamoorthy Parasuram , Sharma Samin K , Dangas George , Fuster Valentin , Mehran Roxana
Published: August 2021

Aims

To evaluate the acute and chronic patterns of myocardial injury among patients with coronavirus disease-2019 (COVID-19), and their mid-term outcomes.

Methods and results

Patients with laboratory-confirmed COVID-19 who had a hospital encounter within the Mount Sinai Health System (New York City) between 27 February 2020 and 15 October 2020 were evaluated for inclusion. Troponin levels assessed between 72 h before and 48 h after the COVID-19 diagnosis were used to stratify the study population by the presence of acute and chronic myocardial injury, as defined by the Fourth Universal Definition of Myocardial Infarction. Among 4695 patients, those with chronic myocardial injury (n = 319, 6.8%) had more comorbidities, including chronic kidney disease and heart failure, while acute myocardial injury (n = 1168, 24.9%) was more associated with increased levels of inflammatory markers. Both types of myocardial injury were strongly associated with impaired survival at 6 months [chronic: hazard ratio (HR) 4.17, 95% confidence interval (CI) 3.44–5.06; acute: HR 4.72, 95% CI 4.14–5.36], even after excluding events occurring in the first 30 days (chronic: HR 3.97, 95% CI 2.15–7.33; acute: HR 4.13, 95% CI 2.75–6.21). The mortality risk was not significantly different in patients with acute as compared with chronic myocardial injury (HR 1.13, 95% CI 0.94–1.36), except for a worse prognostic impact of acute myocardial injury in patients <65 years of age (P-interaction = 0.043) and in those without coronary artery disease (P-interaction = 0.041).

Conclusion

Chronic and acute myocardial injury represent two distinctive patterns of cardiac involvement among COVID-19 patients. While both types of myocardial injury are associated with impaired survival at 6 months, mortality rates peak in the early phase of the infection but remain elevated even beyond 30 days during the convalescent phase.
Efficacy of a digital therapeutics system in the management of essential hypertension: the HERB-DH1 pivotal trial
Authors: Kario Kazuomi , Nomura Akihiro , Harada Noriko , Okura Ayako , Nakagawa Kiyose , Tanigawa Tomoyuki , Hida Eisuke
Published: August 2021

Aims

Digital therapeutics is a new approach to facilitate the non-pharmacological treatment of hypertension using software programmes such as smartphone applications and/or device algorithms. Based on promising findings from a small pilot trial, the HERB Digital Hypertension 1 (HERB-DH1) pivotal trial investigated the efficacy of digital therapeutics in patients with hypertension not receiving antihypertensive medication.

Methods and results

This prospective, open-label, randomized controlled study was performed at 12 sites in Japan. Patients with hypertension [office systolic blood pressure (SBP) 140 to <180 mmHg and 24 h SBP ≥130 mmHg] were randomly assigned 1:1 to the digital therapeutics group (HERB system + standard lifestyle modification) or control group (standard lifestyle modification alone). The primary efficacy endpoint was the mean change in 24 h ambulatory SBP from baseline to 12 weeks; key secondary efficacy endpoints were mean changes in office and home blood pressure (BP) from baseline to 12 weeks. All analyses were conducted in the full analysis set population. Between December 2019 and June 2020, 390 patients were randomly assigned to the digital therapeutics group (n = 199) or control (n = 191) group. Between-group differences in 24-h ambulatory, home, and office SBPs at 12 weeks were −2.4 (95% confidence interval −4.5 to −0.3), −4.3 (−6.7 to −1.9), and −3.6 (−6.2 to −1.0) mmHg, respectively. No major programme-related safety events occurred up to 24 weeks.

Conclusion

The HERB-DH1 pivotal study showed the superiority of digital therapeutics compared with standard lifestyle modification alone to reduce 24-h ambulatory, home, and office BPs in the absence of antihypertensive medications.
Phenotypic heterogeneity in persisters: a novel ‘hunker’ theory of persistence
Authors: Urbaniec J , Xu Ye , Hu Y , Hingley-Wilson S , McFadden J
Published: August 2021

Persistence has been linked to treatment failure since its discovery over 70 years ago and understanding formation, nature and survival of this key antibiotic refractory subpopulation is crucial to enhancing treatment success and combatting the threat of antimicrobial resistance (AMR). The term ‘persistence’ is often used interchangeably with other terms such as tolerance or dormancy. In this review we focus on ‘antibiotic persistence’ which we broadly define as a feature of a subpopulation of bacterial cells that possesses the non-heritable character of surviving exposure to one or more antibiotics; and persisters as cells that possess this characteristic. We discuss novel molecular mechanisms involved in persister cell formation, as well as environmental factors which can contribute to increased antibiotic persistence in vivo, highlighting recent developments advanced by single-cell studies. We also aim to provide a comprehensive model of persistence, the ‘hunker’ theory which is grounded in intrinsic heterogeneity of bacterial populations and a myriad of ‘hunkering down’ mechanisms which can contribute to antibiotic survival of the persister subpopulation. Finally, we discuss antibiotic persistence as a ‘stepping-stone’ to AMR and stress the urgent need to develop effective anti-persister treatment regimes to treat this highly clinically relevant bacterial sub-population.
Multiparameter viscoelastic full-waveform inversion of shallow-seismic surface waves with a pre-conditioned truncated Newton method
Authors: Gao Lingli , Pan Yudi , Rieder Andreas , Bohlen Thomas
Published: August 2021

2-D full-waveform inversion (FWI) of shallow-seismic Rayleigh waves has become a powerful method for reconstructing viscoelastic multiparameter models of shallow subsurface with high resolution. The multiparameter reconstruction in FWI is challenging due to the potential presence of cross-talk between different parameters and the unbalanced sensitivity of Rayleigh-wave data with respect to different parameter classes. Accounting for the inverse Hessian using truncated Newton methods based on second-order adjoint methods provides an effective tool to mitigate cross-talk caused by the coupling between different parameters. In this study, we apply a pre-conditioned truncated Newton (PTN) method to shallow-seismic FWI to simultaneously invert for multiparameter near-surface models (P- and S-wave velocities, attenuation of P and S waves, and density). We first investigate scattered wavefields caused by these parameters to evaluate the coupling between them. Then we investigate the performance of the PTN method on shallow-seismic FWI of Rayleigh wave for reconstructing all five parameters simultaneously. The application to spatially correlated and uncorrelated models demonstrates that the PTN method helps to mitigate the cross-talk and improves the resolution of the multiparameter reconstructions, especially for the weak parameters with small sensitivity such as attenuation and density parameters. The attenuation of Pwaves cannot be inverted reliably due to its negligible sensitivity on the Rayleigh wave. The comparison with the classical pre-conditioned conjugate gradient method highlights the improved performance of the PTN method and thus the benefit of accounting for the information included in the Hessian.
Opportunistic magnetotelluric transects from CSEM surveys in the Barents Sea
Authors: Corseri R , Planke S , Faleide J I , Senger K , Gelius L J , Johansen S E
Published: August 2021

Magnetotelluric (MT) data allow for electrical resistivity probing of the Earth's subsurface. Integration of resistivity models in passive margin studies could help disambiguate non-unique interpretations of crustal composition derived from seismic and potential field data, a recurrent issue in the distal domain. In this contribution, we present the first marine MT data in the Barents Sea, derived from industrial controlled-source electromagnetic (CSEM) surveys. We characterize data quality, dimensionality, depth penetration and elaborate an analysis strategy. The extensive MT database consists of 337 receivers located along 7 regional transects, emanating from ∼70,000 km2 of 3D CSEM surveys acquired for hydrocarbon exploration from 2007 to 2019. High-quality MT data are extracted for periods ranging from 0.5 s to 5000 s. The data show no apparent contamination by the active source nor effects related to large time-gaps in data collection and variable solar activity. Along receiver profiles, abrupt lateral variations of apparent resistivity and phase trends coincide with major structural boundaries and underline the geological information contained in the data. Dimensionality analysis reveals a dichotomy between the western domain of the SW Barents Sea, dominated by a single N-S electromagnetic strike, and the eastern domain, with a two-fold, period-dependent strike. 35 receivers show 3D distortion caused by nearby bathymetric slopes, evidenced by elevated skew values. We delineate geographical areas where the 2D assumption is tenable and lay the foundation for future MT modelling strategies in the SW Barents Sea. We performed 2D MT inversion along one of the regional transects, a ∼220 km-long, E-W profile encompassing a major structural high and sedimentary basin approaching the continent-ocean transition. The resistivity model reveals low crustal resistivity values (1–10 Ω.m) beneath the deep sedimentary basins, in marked contrast with high resistivity values (1000–5000 Ω.m) of the thick crystalline crust on the structural high. We interpret this abrupt lateral resistivity variation as a rapid transition from a thick, dry continental crust to a hyperextended and hydrated crustal domain. Integration of resistivity with seismic velocity, density and magnetic susceptibility models may further refine these structural models and the underlying tectonic processes in the SW Barents Sea margin. Our methodology is applicable globally where 3D CSEM surveys are acquired and has a large potential for harvesting new knowledge on the electrical resistivity properties of the lithosphere.
Characterization of Skeletal Phenotype and Associated Mechanisms With Chronic Intestinal Inflammation in theWinnieMouse Model of Spontaneous Chronic Colitis
Authors: Al Saedi Ahmed , Sharma Shilpa , Bani Hassan Ebrahim , Chen Lulu , Ghasem-Zadeh Ali , Hassanzadeganroudsari Majid , Gooi Jonathan H , Stavely Rhian , Eri Rajaraman , Miao Dengshun , Nurgali Kulmira , Duque Gustavo
Published: August 2021

Background

Osteoporosis is a common extraintestinal manifestation of inflammatory bowel disease (IBD). However, studies have been scarce, mainly because of the lack of an appropriate animal model of colitis-associated bone loss. In this study, we aimed to decipher skeletal manifestations in the Winnie mouse model of spontaneous chronic colitis, which carries a MUC2 gene mutation and closely replicates ulcerative colitis. In our study, Winnie mice, prior to the colitis onset at 6 weeks old and progression at 14 and 24 weeks old, were compared with age-matched C57BL/6 controls. We studied several possible mechanisms involved in colitis-associated bone loss.

Methods

We assessed for bone quality (eg, microcomputed tomography [micro-CT], static and dynamic histomorphometry, 3-point bending, and ex vivo bone marrow analysis) and associated mechanisms (eg, electrochemical recordings for gut-derived serotonin levels, real-time polymerase chain reaction [qRT-PCR], double immunofluorescence microscopy, intestinal inflammation levels by lipocalin-2 assay, serum levels of calcium, phosphorus, and vitamin D) from Winnie (6–24 weeks) and age-matched C57BL6 mice.

Results

Deterioration in trabecular and cortical bone microarchitecture, reductions in bone formation, mineral apposition rate, bone volume/total volume, osteoid volume/bone surface, and bone strength were observed in Winnie mice compared with controls. Decreased osteoblast and increased osteoclast numbers were prominent in Winnie mice compared with controls. Upregulation of 5-HTR1B gene and increased association of FOXO1 with ATF4 complex were identified as associated mechanisms concomitant to overt inflammation and high levels of gut-derived serotonin in 14-week and 24-week Winnie mice.

Conclusions

Skeletal phenotype of the Winnie mouse model of spontaneous chronic colitis closely represents manifestations of IBD-associated osteoporosis/osteopenia. The onset and progression of intestinal inflammation are associated with increased gut-derived serotonin level, increased bone resorption, and decreased bone formation.
Physiological Variation in Response to Vibrio and Hypoxia by Aquacultured Eastern Oysters in the Southeastern United States
Authors: Furr Denise , Ketchum Remi N , Phippen Britney L , Reitzel Adam M , Ivanina Anna V
Published: August 2021

Synopsis

Eastern oysters (Crassostrea virginica) have long been recognized as model organisms of extreme environmental tolerance, showing resilience to variation in temperature, salinity, hypoxia, and microbial pathogens. These phenotypic responses, however, show variability between geographic locations or habitats (e.g., tidal). Physiological, morphological, and genetic differences occur in populations throughout a species’ geographical range, which may have been shaped by regional abiotic and biotic variations. Few studies of C. virginica have explored the combined factors of physiological mechanisms of divergent phenotypes between locations and the genetic relationships of individuals between these locations. To characterize genetic relationships of four locations with aquacultured oysters along the North Carolina and Virginia coast, we sequenced a portion of cytochrome oxidase subunit I (COI) that revealed significant variation in haplotype distribution between locations. We then measured mitochondrial physiology and expression of the innate immunity response of hemocytes to lab acclimation and combined stress conditions to compare basal expression and stress response in oysters between these locations. For stress sensing genes, toll-like receptors had the strongest location-specific response to hypoxia and Vibrio, whereas mannose receptor and a stress-receptor were specific to hypoxia and bacteria, respectively. The expression of stress response genes also showed location-specific and stressor-specific changes in expression, particularly for big defensin and the complement gene Cq3. Our results further suggested that genetic similarity of oysters from different locations was not clearly related to physiological and molecular responses. These results are informative for understanding the range of physiological plasticity for stress responses in this commercially important oyster species. They also have implications in the oyster farming industry as well as conservation efforts to restore endangered native oyster beds.
Trade-offs Among Resilience, Robustness, Stability, and Performance and How We Might Study Them
Authors: Inouye Brian D , Brosi Berry J , Le Sage Emily H , Lerdau Manuel T
Published: August 2021

Synopsis

Biological systems are likely to be constrained by trade-offs among robustness, resilience, and performance. A better understanding of these trade-offs is important for basic biology, as well as applications where biological systems can be designed for different goals. We focus on redundancy and plasticity as mechanisms governing some types of trade-offs, but mention others as well. Whether trade-offs are due to resource constraints or “design” constraints (i.e., structure of nodes and links within a network) will also affect the types of trade-offs that are important. Identifying common themes across scales of biological organization will require that researchers use similar approaches to quantifying robustness, resilience, and performance, using units that can be compared across systems.
Paracetamol: unconventional uses of a well-known drug
Authors: Bloukh Sarah , Wazaify Mayyada , Matheson Catriona
Published: August 2021

Objectives

To describe and map what is known about unconventional uses of paracetamol through a scoping review of published literature by adopting adopted a PRISMA systematic approach methodology.

Key findings

Four themes for unconventional uses of paracetamol emerged: (a) use of paracetamol in sleep (a-1) positive effect of paracetamol on sleep (n = 9) or (a-2) neutral or negative effect of paracetamol on sleep (n = 9); (b) use of paracetamol in sport (n = 13); (c) mixing paracetamol with drinks, waterpipe and illicit drugs (n = 5); and (d) miscellaneous uses (n = 4). Forty records were reviewed and charted. Available literature supports concern around the potential of harmful or non-medical use of paracetamol, especially among patients with a history of substance use, parents of young children or athletes.

Paracetamol (acetaminophen) is one of the most popular and widely used drugs for the treatment of pain and fever. It is considered remarkably safe if used within instructions. However, there is growing evidence that paracetamol, is sometimes used outside approved indications or abused (i.e. used for non-medical reasons). This review highlights the need for enhanced pharmacovigilance and surveillance of non-medical paracetamol use and raising general public awareness of its potential dangers especially in higher than recommended doses.