bluuebunny/crossref_metadata_2025 huggingface dataset:
Forecasts on interacting dark energy from the 21-cm angular power spectrum with BINGO and SKA observations
Authors: Xiao Linfeng , Costa Andre A , Wang Bin
Published: November 2021

Neutral hydrogen (H i) intensity mapping is a promising technique to probe the large-scale structure of the Universe, improving our understanding of the late-time accelerated expansion. In this work, we first scrutinize how an alternative cosmology, interacting dark energy (IDE), can affect the 21-cm angular power spectrum relative to the concordance ΛCDM model. We re-derive the 21-cm brightness temperature fluctuation in the context of such an interaction and uncover an extra new contribution. Then we estimate the noise level of three upcoming H i intensity mapping surveys, namely Baryon Acoustic Oscillations from Integrated Neutral Gas Observations (BINGO), Square Kilometre Array (SKA1)-MID Band 1 and Band 2, and employ a Fisher matrix approach to forecast their constraints on the IDE model. We find that while Planck 2018 maintains its dominion over early-Universe parameter constraints, BINGO and SKA1-MID Band 2 provide complementary bounding to the latest cosmic microwave background measurements on the dark energy equation of state w, the interacting strength λi and the reduced Hubble constant h, and that SKA1-MID Band 1 even outperforms Planck 2018 in these late-Universe parameter constraints. The expected minimum uncertainties are given by SKA1-MID Band 1 + Planck: $\sim 0.34{{\ \rm per\ cent}}$ on w, $\sim 0.22{{\ \rm per\ cent}}$ on h, $\sim 0.64{{\ \rm per\ cent}}$ on H i bias bHi, and an absolute uncertainty of about 3 × 10−4 (7 × 10−4) on λ1 (λ2). Moreover, we quantify the effects from systematics of the redshift bin number, redshift-space distortions, foreground residuals and uncertainties on the measured H i fraction, ΩHi(z). Our results indicate a bright prospect for H i intensity mapping surveys in constraining IDE, whether on their own or by synergies with other measurements.
Addiction-Related Outcomes of Nicotine and Alcohol Co-use: New Insights Following the Rise in Vaping
Authors: Frie Jude A , Nolan Caitlin J , Murray Jennifer E , Khokhar Jibran Y
Published: November 2021

Purpose

Nicotine and alcohol-containing products are some of the most commonly used substances of abuse and are both leading causes of preventable death. These substances also have significant interactions that have additive and, in some cases, multiplicative effects on the health consequences of their use. Thus, to reduce these negative consequences, it is important to understand the abuse liability of nicotine and alcohol in combination, especially in the most relevant use cases among those who are most vulnerable. Specifically, as tobacco cigarette use is continually decreasing, vaping is quickly replacing cigarettes as the primary mode of nicotine use. This pattern is especially true in adolescent populations in which vaping has grown considerably. Particularly concerning is that adolescents are more vulnerable than adults to the negative consequences of substance use. It is therefore imperative to revisit the literature as it relates to the rising state of co-use of vaping products with alcohol. Here, we review the clinical outcomes of nicotine and alcohol co-use as they relate to the abuse liability of each individually. Special attention is paid to adolescent findings, where available, as well as investigations that use nontobacco nicotine products as these may more accurately reflect the more recent trends of co-use.

Implications

Though nicotine alone has previously been considered a proxy for tobacco and tobacco cigarette use, combustible routes of administration have been decreasing. They are, instead, being replaced by e-cigarettes that do not involve other tobacco constituents and contain additional nonnicotine constituents of their own. Unfortunately, the literature remains limited with regard to e-cigarettes and their interactions with other substances, especially their prevalent co-use with alcohol. This review attempts to discuss the current literature on nicotine and alcohol co-use in the context of the vaping epidemic, predominantly focusing on addiction-related outcomes and why e-cigarette use may be unique.
Damage sensitivity and stability in international environmental agreements
Authors: Eckert Heather , Nkuiya Bruno
Published: November 2021

This article examines the formation of International Environmental Agreements (IEAs). The economic literature focuses on scenarios where countries are weakly sensitive to environmental damages (constant or linear marginal damages) and finds that stable coalitions are small when countries choose their emission strategies simultaneously and the marginal benefit function is linear. Motivated by empirical evidence, our analysis addresses cases where countries are highly sensitive to environmental damages. In this context, we find equilibrium behaviors that reverse conventional wisdom. For instance, large coalitions including the grand coalition can be supported as an equilibrium outcome when the sensitivity of countries to environmental conditions its high. Our findings provide an additional explanation for large-scale IEAs such as the Montreal Protocol.
Subsequent Antituberculous Treatment May Not Be Mandatory Among Surgically Resected Culture-Negative Pulmonary Granulomas: A Retrospective Nationwide Multicenter Cohort Study
Authors: Chung Che-Liang , Huang Wei-Chang , Huang Hung-Ling , Chin Chun-Shih , Cheng Meng-Hsuan , Lee Meng-Rui , Lin Sheng-Hao , Wang Jann-Yuan , Lin Ching-Hsiung , Chong Inn-Wen , Shih Jin-Yuan , Yu Chong-Jen
Published: November 2021

Background

Histologic diagnosis of granuloma is often considered clinically equivalent to a definite diagnosis of pulmonary tuberculosis (TB) in endemic areas. Optimal management of surgically resected granulomatous inflammation in lung with negative mycobacterial culture results, however, remains unclear.

Methods

From 7 medical institutions in northern, middle, and southern Taiwan between January 2010 and December 2018, patients whose surgically resected pulmonary nodule(s) had histological features suggestive of TB but negative microbiological study results and who received no subsequent anti-TB treatment were identified retrospectively. All patients were followed up for 2 years until death or active TB disease was diagnosed.

Results

A total of 116 patients were enrolled during the study period. Among them, 61 patients (52.6%) were clinically asymptomatic, and 36 (31.0%) patients were immunocompromised. Solitary pulmonary nodule accounted for 44 (39.6%) of all cases. The lung nodules were removed by wedge resection in 95 (81.9%), lobectomy in 17 (14.7%), and segmentectomy in 4 (3.4%) patients. The most common histological feature was granulomatous inflammation (n=116 [100%]), followed by caseous necrosis (n=39 [33.6%]). During follow-up (218.4 patient-years), none of the patients developed active TB.

Conclusions

In patients with surgically resected culture-negative pulmonary granulomas, the incidence rate of subsequent active TB is low. Watchful monitoring along with regular clinical, radiological, and microbiological follow-up, instead of routine anti-TB treatment, may also be a reasonable option.
A NYN domain protein directly interacts with DECAPPING1 and is required for phyllotactic pattern
Authors: Schiaffini Marlene , Chicois Clara , Pouclet Aude , Chartier Tiphaine , Ubrig Elodie , Gobert Anthony , Zuber Hélène , Mutterer Jérôme , Chicher Johana , Kuhn Lauriane , Hammann Philippe , Gagliardi Dominique , Garcia Damien
Published: November 2021

In eukaryotes, general mRNA decay requires the decapping complex. The activity of this complex depends on its catalytic subunit, DECAPPING2 (DCP2), and its interaction with decapping enhancers, including its main partner DECAPPING1 (DCP1). Here, we report that in Arabidopsis thaliana, DCP1 also interacts with a NYN domain endoribonuclease, hence named DCP1-ASSOCIATED NYN ENDORIBONUCLEASE 1 (DNE1). Interestingly, we found DNE1 predominantly associated with DCP1, but not with DCP2, and reciprocally, suggesting the existence of two distinct protein complexes. We also showed that the catalytic residues of DNE1 are required to repress the expression of mRNAs in planta upon transient expression. The overexpression of DNE1 in transgenic lines led to growth defects and a similar gene deregulation signature than inactivation of the decapping complex. Finally, the combination of dne1 and dcp2 mutations revealed a functional redundancy between DNE1 and DCP2 in controlling phyllotactic pattern formation. Our work identifies DNE1, a hitherto unknown DCP1 protein partner highly conserved in the plant kingdom and identifies its importance for developmental robustness.
Diffuse idiopathic skeletal hyperostosis is associated with incident stroke in patients with increased cardiovascular risk
Authors: Harlianto Netanja I , Oosterhof Nadine , Foppen Wouter , Hol Marjolein E , Wittenberg Rianne , van der Veen Pieternella H , van Ginneken Bram , Mohamed Hoesein Firdaus A A , Verlaan Jorrit-Jan , de Jong Pim A , Westerink Jan ,   for the UCC-SMART-Studygroup, van Petersen R , van Dinther B , Asselbergs F W , Nathoe H M , de Borst G J , Bots M L , Geerlings M I , Emmelot M H , de Jong P A , Leiner T , Lely A T , van der Kaaij N P , Kappelle L J , Ruigrok Y M , Verhaar M C , Visseren F L J , Westerink J
Published: November 2021

Objectives

Earlier retrospective studies have suggested a relation between DISH and cardiovascular disease, including myocardial infarction. The present study assessed the association between DISH and incidence of cardiovascular events and mortality in patients with high cardiovascular risk.

Methods

In this prospective cohort study, we included 4624 patients (mean age 58.4 years, 69.6% male) from the Second Manifestations of ARTerial disease cohort. The main end point was major cardiovascular events (MACE: stroke, myocardial infarction and vascular death). Secondary endpoints included all-cause mortality and separate vascular events. Cause-specific proportional hazard models were used to evaluate the risk of DISH on all outcomes, and subdistribution hazard models were used to evaluate the effect of DISH on the cumulative incidence. All models were adjusted for age, sex, body mass index, blood pressure, diabetes, non-HDL cholesterol, packyears, renal function and C-reactive protein.

Results

DISH was present in 435 (9.4%) patients. After a median follow-up of 8.7 (IQR 5.0–12.0) years, 864 patients had died and 728 patients developed a MACE event. DISH was associated with an increased cumulative incidence of ischaemic stroke. After adjustment in cause-specific modelling, DISH remained significantly associated with ischaemic stroke (HR 1.55; 95% CI: 1.01, 2.38), but not with MACE (HR 0.99; 95% CI: 0.79, 1.24), myocardial infarction (HR 0.88; 95% CI: 0.59, 1.31), vascular death (HR 0.94; 95% CI: 0.68, 1.27) or all-cause mortality (HR 0.94; 95% CI: 0.77, 1.16).

Conclusion

The presence of DISH is independently associated with an increased incidence and risk for ischaemic stroke, but not with MACE, myocardial infarction, vascular death or all-cause mortality.
Association of anti-HSC70 autoantibodies with cutaneous ulceration and severe disease in juvenile dermatomyositis
Authors: Karasawa Rie , Yudoh Kazuo , Sato Toshiko , Tanaka Megumi , Tamaki Mayumi , Sabbagh Sara E , O’Hanlon Terrance P , Noroozi-Farhadi Payam , Targoff Ira N , Flegel Willy A , Mammen Andrew L , Miller Frederick W , Hicar Mark D , Rider Lisa G , Jarvis James N
Published: November 2021

Objectives

JDM is an inflammatory myopathy characterized by prominent vasculopathy. AECAs are frequently detected in inflammatory and autoimmune diseases. We sought to determine whether AECAs correlate with clinical features of JDM, and thus serve as biomarkers to guide therapy or predict outcome.

Methods

Plasma samples from 63 patients with JDM, 49 patients with polyarticular JIA and 40 juvenile healthy controls were used to detect anti-heat shock cognate 71 kDa protein (HSC70) autoantibodies, a newly identified AECA, in ELISA assays. Clinical features were compared between JDM patients with and without anti-HSC70 autoantibodies.

Results

Anti-HSC70 autoantibodies were detected in 35% of patients with JDM, in 0% of patients with JIA (P < 0.0001) and in 0% of healthy donors (P < 0.0001). Both the presence of cutaneous ulcers (59% vs 17%, P < 0.002) and the use of wheelchairs and/or assistive devices (64% vs 27%, P < 0.007) were strongly associated with anti-HSC70 autoantibodies in JDM. High scores on the severity of myositis damage measures at the time of measurement of anti-HSC70 autoantibodies and an increased number of hospitalizations were also associated with anti-HSC70 autoantibodies. Intravenous immunoglobulin therapy was used more often in anti-HSC70 autoantibody-positive patients.

Conclusion

Anti-HCS70 autoantibodies are detected frequently in children with JDM and are novel myositis-associated autoantibodies correlating with disease severity.
Ebola virus disease in pregnancy: a systematic review and meta-analysis
Authors: Kayem Nzelle D , Benson Charlotte , Aye Christina Y L , Barker Sarah , Tome Mariana , Kennedy Stephen , Ariana Proochista , Horby Peter
Published: November 2021

This review synthesises and appraises evidence on the effects of Ebola virus disease (EVD) in pregnancy. We searched bibliographic databases from dates of inception to November 2020, yielding 28 included studies.

The absolute risk of maternal death associated with EVD was estimated at 67.8% (95% confidence interval [CI] 49.8 to 83.7, I2=85%, p<0.01) and the relative risk of death in pregnant women compared with non-pregnant women was estimated at 1.18 (95% CI 0.59 to 2.35, I2=31.0%, p=0.230). The absolute risk for foetal losses was estimated at 76.9% (95% CI 45.0 to 98.3, I2=96%, p<0.01) and neonatal death was 98.5% (95% CI 84.9 to 100, I2=0.0%, p=0.40). The gap analysis suggests limited or no data on the clinical course, non-fatal perinatal outcomes and EVD management in pregnant women. The review suggests that EVD has a high maternal and perinatal mortality, underscoring the urgent need for preventative and therapeutic solutions and improved screening and follow-up of pregnant women and newborns during outbreaks. There is not enough evidence to conclusively rule out pregnancy as a risk factor for mortality and there is limited evidence on the disease course, outcomes and management of EVD in pregnancy, and this supports the need for robust clinical trials and prospective studies that include pregnant women.
Vacuum Steam Treatment of Metrosideros polymorpha Logs for Eradication of Ceratocystis huliohia and C. lukuohia
Authors: Juzwik Jennifer , Hughes Marc A. , Chen Zhangjing , Yang Anna , Keith Lisa M. , White Marshall S.
Published: November 2021

A new and devastating disease, rapid ohia death (ROD), in Hawaii led to a state quarantine that regulates interisland transport of ohia wood and plant material to prevent spread of the causal pathogens. Heat treatments of ohia logs in commercial trade were considered for phytosanitary treatment. Vacuum steam (VS) was evaluated for its ability to eradicate the pathogens, Ceratocystis lukuohia and C. huliohia, in main stem logs from ROD-affected forest trees. Replicate loads of three debarked logs (24 to 43 cm in diameter, 1.7 to 2.0 m long) were VS treated at 56°C for 30 min (five loads) or 60°C for 60 min (four loads) at a sapwood depth equal to 70% of log radius. Percentage isolation of Ceratocystis from VS and ambient temperature logs before treatment and summarized by source tree ranged from 12 to 66% and 6 to 31% based on carrot baiting assays of tissue taken from outer and inner sapwood, respectively. No viable Ceratocystis was detected in sapwood locations for the 60°C/60 min schedule or inner locations for the 56°C/30 min schedule after treatment. Only one subsample (0.48%, n = 208) of the latter schedule treatment yielded Ceratocystis. Time needed for treatment ranged from 7.4 to 15 h for the 56°C/30 min schedule and from 8.6 to 19.2 h for the 60°C/60 min schedule. These results demonstrate that VS is an effective and efficient method for treating large-diameter ohia logs that mill owners and regulatory plant pathologists may consider for use in Hawaii.
Etiology of Botryosphaeria Panicle and Shoot Blight of Pistachio (Pistacia vera) Caused by Botryosphaeriaceae in Italy
Authors: Gusella Giorgio , Lawrence Daniel P. , Aiello Dalia , Luo Yong , Polizzi Giancarlo , Michailides Themis J.
Published: November 2021

Pistachio (Pistacia vera) is an important crop in Italy, traditionally cultivated in Sicily (southern Italy) for several decades now. In recent years, new orchards have been planted in new areas of the island. Field surveys conducted in 2019 revealed the presence of symptomatic trees showing shoot dieback, cankers, fruit spots, and leaf lesions. Isolations from symptomatic samples consistently yielded fungal species in the Botryosphaeriaceae family. Identification of collected isolates was conducted using morphological and molecular analyses. Morphological characterization was based on conidia measurements of representative isolates and also effects of temperatures on mycelial growth was evaluated. DNA data derived from sequencing the ITS, tef1-α, and tub2 gene regions were analyzed via phylogenetic analyses (maximum parsimony and maximum likelihood). Results of the analyses confirmed the identity of Botryosphaeria dothidea, Neofusicoccum hellenicum, and N. mediterraneum. Pathogenicity tests were conducted on detached twigs and in the fields both on shoots as well as on fruit clusters using the mycelial plug technique. The inoculation experiments revealed that among the Botryosphaeriaceae species identified in this study N. hellenicum (occasionally detected) and N. mediterraneum were the most aggressive based on lesion length on shoots and fruits. N. mediterraneum was the most widespread among the orchards while B. dothidea can be considered a minor pathogen involved in this complex disease of pistachio. Moreover, to our knowledge, this is the first report of N. hellenicum in Italy.
Ribosome dysfunction in osteoarthritis
Authors: van den Akker Guus G.H. , Caron Marjolein M.J. , Peffers Mandy J. , Welting Tim J.M.
Published: November 2021

Purpose of review

Translation of genetic information encoded within mRNA molecules by ribosomes into proteins is a key part of the central dogma of molecular biology. Despite the central position of the ribosome in the translation of proteins, and considering the major proteomic changes that occur in the joint during osteoarthritis development and progression, the ribosome has received very limited attention as driver of osteoarthritis pathogenesis.

Recent findings

We provide an overview of the limited literature regarding this developing topic for the osteoarthritis field. Recent key findings that connect ribosome biogenesis and activity with osteoarthritis include: ribosomal RNA transcription, processing and maturation, ribosomal protein expression, protein translation capacity and preferential translation.

The ribosome as the central cellular protein synthesis hub is largely neglected in osteoarthritis research. Findings included in this review reveal that in osteoarthritis, ribosome aberrations have been found from early-stage ribosome biogenesis, through ribosome build-up and maturation, up to preferential translation. Classically, osteoarthritis has been explained as an imbalance between joint tissue anabolism and catabolism. We postulate that osteoarthritis can be interpreted as an acquired ribosomopathy. This hypothesis fine-tunes the dogmatic anabolism/katabolism point-of-view, and may provide novel molecular opportunities for the development of osteoarthritis disease-modifying treatments.
Therapeutic Drug Monitoring of Antibiotics: Defining the Therapeutic Range
Authors: Abdul–Aziz Mohd H. , Brady Kara , Cotta Menino Osbert , Roberts Jason A.
Published: November 2021

Purpose:

In the present narrative review, the authors aimed to discuss the relationship between the pharmacokinetic/pharmacodynamic (PK/PD) of antibiotics and clinical response (including efficacy and toxicity). In addition, this review describes how this relationship can be applied to define the therapeutic range of a particular antibiotic (or antibiotic class) for therapeutic drug monitoring (TDM).

Methods:

Relevant clinical studies that examined the relationship between PK/PD of antibiotics and clinical response (efficacy and response) were reviewed. The review (performed for studies published in English up to September 2021) assessed only commonly used antibiotics (or antibiotic classes), including aminoglycosides, beta-lactam antibiotics, daptomycin, fluoroquinolones, glycopeptides (teicoplanin and vancomycin), and linezolid. The best currently available evidence was used to define the therapeutic range for these antibiotics.

Results:

The therapeutic range associated with maximal clinical efficacy and minimal toxicity is available for commonly used antibiotics, and these values can be implemented when TDM for antibiotics is performed. Additional data are needed to clarify the relationship between PK/PD indices and the development of antibiotic resistance.

Conclusions:

TDM should only be regarded as a means to achieve the main goal of providing safe and effective antibiotic therapy for all patients. The next critical step is to define exposures that can prevent the development of antibiotic resistance and include these exposures as therapeutic drug monitoring targets.
Assessment of coronary inflammation in antiretroviral treated people with HIV infection and active HIV/hepatitis C virus co-infection
Authors: Jeudy Jean , Patel Pratik , George Nivya , Burrowes Shana , Husson Jennifer , Chua Joel , Conn Lora , Weiss Robert G. , Bagchi Shashwatee
Published: November 2021

Objective:

People with HIV (PWH) and co-infected with hepatitis C virus (PWH + HCV) have increased risk of cardiovascular disease (CVD). Peri-coronary inflammation, measured by fat attenuation index (FAI) on coronary computed tomography angiography (CCTA), independently predicts cardiovascular risk in the general population but has not been studied in the PWH + HCV population. We tested whether peri-coronary inflammation is increased in PWH or PWH + HCV, and whether inflammation changes over time.

Design:

Cross-sectional analysis to determine FAI differences among groups. Longitudinal analysis in PWH to assess changes in inflammation over time.

Methods:

Age-matched and sex-matched seropositive groups (PWH and PWH + HCV) virologically suppressed on antiretroviral therapy, HCV viremic, and without prior CVD and matched controls underwent CCTA. Peri-coronary FAI was measured around the proximal right coronary artery (RCA) and left anterior descending artery (LAD). Follow-up CCTA was performed in 22 PWH after 20.6–27.4 months.

Results:

A total of 101 participants (48 women) were studied (60 PWH, 19 PWH + HCV and 22 controls). In adjusted analyses, peri-coronary FAI did not differ between seropositive groups and controls. Low attenuation coronary plaque was significantly less common in seropositive groups compared with controls (LAD, P = 0.035; and RCA, P = 0.017, respectively). Peri-coronary FAI values significantly progressed between baseline and follow-up in PWH (RCA: P = 0.001, LAD: P = <0.001).

Conclusion:

PWH and PWH + HCV without history of CVD do not have significantly worse peri-coronary inflammation, assessed by FAI, compared with matched controls. However, peri-coronary inflammation in mono-infected PWH significantly increased over approximately 22 months. FAI measures may be an important imaging biomarker for tracking asymptomatic CVD progression in PWH.
Isolation and characterization of Campylobacter massiliensis sp. nov., a novel Campylobacter species detected in a gingivitis subject
Authors: Antezack Angéline , Boxberger Manon , Rolland Clara , Ben Khedher Mariem , Monnet-Corti Virginie , La Scola Bernard
Published: November 2021

A Gram-negative bacterium, designated strain Marseille-Q3452T, was isolated from subgingival dental plaque of a subject suffering from dental plaque bioﬁlm-induced gingivitis on an intact periodontium in Marseille, France. The strain was characterized by 16S rRNA and atpA gene sequence analysis and by conventional phenotypic and chemotaxonomic testing. The average nucleotide identity (ANI) and core genome phylogeny were determined using whole-genome sequences. Although strain Marseille-Q3452T showed 99.72 % 16S rRNA gene sequence similarity with

Campylobacter showae

strain ATCC 51146T, atpA and ANI analyses revealed divergence between the two strains. The two species could also be distinguished phenotypically on the basis of the absence of flagella and nitrate reduction. On the basis of the results from phenotypic, chemotaxonomic, genomic and phylogenetic analyses and data, we concluded that strain Marseille-Q3452T represents a novel species of the genus

Campylobacter

, for which the name Campylobacter massiliensis sp. nov. is proposed (=CSUR Q3452=CECT 30263).
Quality characteristics and antioxidant activities of
‘Sikhye’ containing different amounts of Jerusalem artichoke
extract
Authors: Kim Hye-Sook , Hwang Eun-Sun
Published: November 2021

This work investigated the quality characteristics and antioxidant activities of
‘Sikhye’ containing 0, 25, 50, and 100% Jerusalem artichoke
extracts (JAE) instead of water. The highest moisture content of
‘Sikhye’ was 82.91-87.93% without JAE addition, which generally
decreased the moisture content. There were no statistically significant
differences in the crude protein and fat contents of ‘Sikhye’ as
functions of the added JAE content. In proportion to the added JAE content, the
sugar content, acidity and turbidity of ‘Sikhye’ increased, and
the pH generally decreased. In chromaticity determination, the lightness
decreased and redness and yellowness increased with increasing the level of JAE,
and the total polyphenol and flavonoid contents increased. The antioxidant
activities measured using DPPH and ABTS radical scavenging activities and
reducing powder were significantly higher than that of the control, and
proportionally increased as the amount of JAE increased. These results provide
basic data for the development of ‘Sikhye’ supplemented with
Jerusalem artichoke.
Ethnic Variation and its Association with Malaria Awareness: A Cross-sectional Study in the East Nusa Tenggara Province (Indonesia)
Authors: Guntur Robertus Dole , Kingsley Jonathan , Islam Fakir M. Amirul
Published: November 2021

Objectives

This study aims to investigate ethnic variation and its association with malaria awareness in the East Nusa Tenggara Province (ENTP), Indonesia.

Methods

A community-based cross-sectional study was conducted upon 1495 adults recruited by multi-stage cluster random sampling technique. A malaria awareness related questionnaire was used to collect data alongside a malaria awareness index (MAI). A logistic regression method was applied to quantify the strength of associations of factors associated with the awareness index.

Results

Of total participants, 33% were from Manggarai, 32.3% were from Atoni, 30.2% from Sumba ethnicity. The level of MAI was significantly different between these groups with the highest in Manggarai ethnicity (65.1%, 95% confidence interval (CI): 59.9 – 70.3) and the lowest in Sumba ethnicity (35%, 95% CI: 27.6 – 42.4). The most prominent factors influencing the MAI in Sumba and Manggarai ethnicity were education level, whilst it was socio-economic status (SES) in Atoni ethnicity. The level of MAI was significantly higher for adults with diploma or above education level (adjusted odds ratio (AOR): 21.4, 95% CI: 3.59 – 127.7-for Manggarai ; AOR: 6.94, 95% CI: 1.81 – 26.6 for Sumba). The level of MAI was significantly higher for adults living in high SES in Atoni (AOR 24.48, 95% CI: 8.79 – 68.21).

Conclusions

Poorer education levels and low SES were more prominent factors contributing to lower levels of MAI in rural ENTP. Interventions should focus on improving malaria awareness to these groups to support the national commitment of the Indonesian government to achieve malaria elimination zone by 2030.
Cardiovascular disease biomarkers derived from circulating cell-free DNA methylation
Authors: Cuadrat Rafael R. C. , Kratzer Adelheid , Arnal Hector Giral , Wreczycka Katarzyna , Blume Alexander , Ebenal Veronika , Mauno Tiina , Osberg Brendan , Moobed Minoo , Hartung Johannes , Seppelt Claudio , Meteva Denitsa , Haghikia Arash , Leistner David , Landmesser Ulf , Akalin Altuna
Published: November 2021

Acute coronary syndromes (ACS) remain a major cause of worldwide mortality. ACS diagnosis is done by a combination of factors, such as electrocardiogram and plasma biomarkers. These biomarkers, however, lack the power to accurately stratify patients into different risk groups. Instead, we used changes in the circulating cell-free DNA (ccfDNA) methylation profiles to estimate the extent of heart injury and the severity of ACS. Our approach relies on the fact that dying cells in acutely damaged tissue release DNA into the blood, causing an increase in the ccfDNA. In addition, each cell type has a distinct DNA methylation profile. We leverage cell type/state specificity of DNA methylation to deconvolute the cell types of origin for ccfDNA and also find DNA methylation-based biomarkers that stratify patient cohorts. The cohorts consisted of healthy subjects, and patients from three ACS conditions: ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina (UA). We have used two cohorts of patients - discovery, and validation, both consisting of the same conditions. We have sequenced the ccfDNA from the discovery cohort using Whole Bisulfite Genome Sequencing (WBGS), to obtain an unbiased overview of plasma DNA methylation profiles. We have found a total of 1,614 differential methylated regions (DMRs) in the three ACS groups. Many of the regions are associated with genes involved in cardiovascular conditions and inflammation. Using linear models, we were able to narrow down to 254 DMRs significantly associated with ACS severity. The reduced list of DMRs enabled a more accurate stratification of ACS patients. The predictive power of the DMRs was validated in the confirmation cohort using targeted methylation sequencing of the validation cohort.
Three doses of COVID-19 mRNA vaccination are safe based on adverse events reported in electronic health records
Authors: Niesen Michiel J.M. , Pawlowski Colin , O’Horo John C. , Challener Doug W. , Silvert Eli , Donadio Greg , Lenehan Patrick J. , Virk Abinash , Swift Melanie D. , Speicher Leigh L. , Gordon Joel , Geyer Holly L. , Halamka John , Venkatakrishnan AJ , Soundararajan Venky , Badley Andrew
Published: November 2021

Recent reports on waning of COVID-19 vaccine induced immunity have led to the approval and roll-out of additional dose and booster vaccinations. At risk individuals are receiving additional vaccine dose(s), in addition to the regimen that was tested in clinical trials. The risks and the adverse event profiles associated with these additional vaccine doses are currently not well understood. Here, we performed a retrospective study analyzing vaccine-associated adverse events using electronic health records (EHRs) of individuals that have received three doses of mRNA-based COVID-19 vaccines (n = 47,999). By comparing symptoms reported in 2-week time periods after each vaccine dose and in a 2-week period before the 1st vaccine dose, we assessed the risk associated with 3rd dose vaccination, for both BNT162b2 and mRNA-1273. Reporting of severe adverse events remained low after the 3rd vaccine dose, with rates of pericarditis (0.01%, 0%-0.02% 95% CI), anaphylaxis (0.00%, 0%-0.01% 95% CI), myocarditis (0.00%, 0%-0.01% 95% CI), and cerebral venous sinus thrombosis (no cases), consistent with earlier studies. Significantly more individuals (p-value < 0.05) report low-severity adverse events after their 3rd dose compared with after their 2nd dose, including fatigue (4.92% after 3rd dose vs 3.47% after 2nd dose), lymphadenopathy (2.89% vs 2.07%), nausea (2.62% vs 2.04%), headache (2.47% vs 2.07%), arthralgia (2.12% vs 1.70%), myalgia (1.99% vs 1.63%), diarrhea (1.70% vs 1.24%), fever (1.11% vs 0.81%), vomiting (1.10% vs 0.80%), and chills (0.47% vs 0.36%). Our results show that although 3rd dose vaccination against SARS-CoV-2 infection led to increased reporting of low-severity adverse events, risk of severe adverse events remained comparable to the standard 2-dose regime. This study provides support for the safety of 3rd vaccination doses of individuals that are at high-risk of severe COVID-19 and breakthrough infection.
Changing molecular epidemiology and characteristics of methicillin-resistant Staphylococcus aureus isolated from bloodstream infections: nationwide surveillance in Japan in 2019
Authors: Kaku Norihito , Sasaki Daisuke , Ota Kenji , Miyazaki Taiga , Yanagihara Katsunori
Published: November 2021

Synopsis

Objectives

Some single-centre studies have reported that MRSA carrying the staphylococcal cassette chromosome mec (SCCmec) type IV has been increasing in bloodstream infections (BSIs) in Japan. Therefore, we conducted nationwide surveillance for MRSA BSI to investigate the extent of such change across Japan.

Methods

We recruited 51 Japanese hospitals from the Japanese Association for Infectious Diseases. MRSA isolates detected in two or more sets of blood cultures were collected between January and September 2019 and subjected to antimicrobial susceptibility testing. Whole-genome sequencing was also performed to determine SCCmec typing and multilocus typing and detect drug-resistance and virulence genes.

Results

Two hundred seventy MRSA isolates were collected from 45 hospitals. The major combination types were ST8 with SCCmec type IV (ST8-IV) (30.7%), ST1-IV (29.6%), ST2725-IV (9.5%), ST764-II (8.1%), and ST5-II (7.8%). However, there were regional differences among the most major types. The most common types in western, eastern, and northern Japan were ST1-IV, ST8-IV, and ST5-II, respectively. ST8-IV, ST1-IV, and ST2725-IV exhibited greater susceptibility to clindamycin and minocycline than ST764-II and ST5-II, but erm(A) was detected in 93.8% and 100% of ST1-IV and ST2725-IV, respectively. Based on drug-resistance and virulence genes, characteristics of ST8-IV were different from those of ST1-IV and ST2725-IV. In addition, there were two major ST8-IV types with different characteristics.

Conclusions

This study revealed that SCCmec type IV replaced SCCmec type II in MRSA BSI. In addition, SCCmec type IV was divided into several types with different characteristics.
Forecasting the COVID-19 Pandemic: Lessons learned and future directions
Authors: Sundar Saketh , Schwab Patrick , Tan Jade Z.H. , Romero-Brufau Santiago , Celi Leo Anthony , Wangmo Dechen , Penna Nicolás Della
Published: November 2021

I.

Abstract

The Coronavirus Disease 2019 (COVID-19) has demonstrated that accurate forecasts of infection and mortality rates are essential for informing healthcare resource allocation, designing countermeasures, implementing public health policies, and increasing public awareness. However, there exist a multitude of modeling methodologies, and their relative performances in accurately forecasting pandemic dynamics are not currently comprehensively understood.

In this paper, we introduce the non-mechanistic MIT-LCP forecasting model, and assess and compare its performance to various mechanistic and non-mechanistic models that have been proposed for forecasting COVID-19 dynamics. We performed a comprehensive experimental evaluation which covered the time period of November 2020 to April 2021, in order to determine the relative performances of MIT-LCP and seven other forecasting models from the United States’ Centers for Disease Control and Prevention (CDC) Forecast Hub.

Our results show that there exist forecasting scenarios well-suited to both mechanistic and non-mechanistic models, with mechanistic models being particularly performant for forecasts that are further in the future when recent data may not be as informative, and non-mechanistic models being more effective with shorter prediction horizons when recent representative data is available. Improving our understanding of which forecasting approaches are more reliable, and in which forecasting scenarios, can assist effective pandemic preparation and management.
Machine prescription for chronic migraine
Authors: Stubberud Anker , Gray Robert , Tronvik Erling , Matharu Manjit , Nachev Parashkev
Published: November 2021

Responsive to treatment individually, chronic migraine remains strikingly resistant collectively, incurring the second-highest population burden of disability worldwide. A heterogeneity of responsiveness, requiring prolonged—currently heuristic— individual evaluation of available treatments, may reflect a diversity of causal mechanisms, or the failure to identify the most important, single causal factor. Distinguishing between these possibilities, now possible through the application of complex modelling to large-scale data, is critical to determining the optimal approach to identifying new interventions in migraine and making the best use of existing ones.

Examining a richly phenotyped cohort of 1446 consecutive unselected patients with chronic migraine, here we use causal multitask Gaussian process models to estimate individual treatment effects across ten classes of preventatives. Such modelling enables us to quantify the accessibility of heterogeneous responsiveness to high-dimensional modelling, to infer the likely scale of the underlying causal diversity. We calculate the treatment effects in the overall population, and the conditional treatment effects among those modelled to respond and compare the true response rates between these two groups. Identifying a difference in response rates between the groups supports a diversity of causal mechanisms. Moreover, we propose a data-driven machine prescription policy, estimating the time-to-response when sequentially trialing preventatives by individualized treatment effects and compare it to expert guideline sequences. All model performances are quantified out-of-sample.

We identify significantly higher true response rates among individuals modelled to respond, compared to the overall population (mean difference of 0.034; 95% CI 0.003 to 0.065; p=0.033), supporting significant heterogeneity of responsiveness and diverse causal mechanisms. The machine prescription policy yields an estimated 35% reduction in time-to-response (3.750 months; 95% CI 3.507 to 3.993; p<0.0001) compared with expert guidelines, with no substantive increase in expense per patient.

We conclude that the highly distributed mode of causation in chronic migraine necessitates high-dimensional modelling for optimal management. Machine prescription should be considered an essential clinical decision-support tool in the future management of chronic migraine.
Ethnicity and outcomes in COVID-19 in the United Kingdom: a systematic review and meta-analysis
Authors: Siddiq Sania , Ahmed Saima , Akram Irfan
Published: November 2021

This systematic review and meta-analysis evaluated the clinical outcomes of COVID-19 disease in the ethnic minorities of the UK in comparison to the White ethnic group. Medline, Embase, Cochrane, MedRxiv, and Prospero were searched for articles published between May 2020 to April 2021. PROSPERO ID: CRD42021248117. Fourteen studies (767177 participants) were included in the review. In the adjusted analysis, the pooled Odds Ratio (OR) for the mortality outcome was higher for the Black (1.83, 95% CI: 1.21-2.76), Asian (1.16, 95% CI: 0.85-1.57), and Mixed and Other (MO) groups (1.12, 95% CI: 1.04-1.20) compared to the White group. The adjusted and unadjusted ORs of intensive care admission were more than double for all ethnicities (OR Black 2.32, 95% CI: 1.73-3.11, Asian 2.34, 95% CI: 1.89-2.90, MO group 2.26, 95% CI: 1.64-3.11). In the adjusted analysis of mechanical ventilation need the ORs were similarly significantly raised (Black group 2.03, 95% CI: 1.80-2.29, Asian group 1.84, 95% CI: 1.20-2.80, MO 2.09, 95% CI: 1.35-3.22). This review confirmed that all ethnic groups in the UK suffered from increased disease severity and mortality with regards to COVID-19. This has urgent public health and policy implications to reduce the health disparities.
Low grade systemic inflammation is a risk factor for infection death: an observational cohort study
Authors: Drozd Michael , Pujades-Rodriguez Mar , Morgan Ann W , Lillie Patrick J , Witte Klaus K , Kearney Mark T , Cubbon Richard M
Published: November 2021

Background

Many diseases are associated with chronic inflammation, resulting in widening indications for anti-inflammatory therapies. Whilst effective as disease modifying agents, these increase the risk of serious infection.

Objective

To determine if low-grade inflammation is associated with fatal infection, irrespective of associated comorbidity or anti-inflammatory therapy.

Design

Observational cohort study

Setting

UK Biobank study

Participants

461,052 people

Interventions

None

Measurements

Incidence rate ratio (IRR) of death from infection, cardiovascular disease, or other causes, adjusted for comorbidities and use of anti-inflammatory therapies, for serum C-reactive protein (CRP) at recruitment.

Results

Low grade inflammation was common in all morbidities considered and was more prevalent as multimorbidity accrued (CRP ≥2mg/L in 23.3% of people without disease and 58.7% with 3+ comorbidities; p<0.001). After adjusting for confounding factors, CRP ≥2mg/L was associated with a higher IRR of infection death (IRR 1.70; 95% confidence interval 1.51-1.92) than cardiovascular death (IRR 1.48; 1.40-1.57) or other causes of death (IRR 1.41; 1.37-1.45); CRP thresholds of ≥5 and ≥10 mg/L yielded similar findings. Absolute rates of infection, cardiovascular and other death were 0.43, 1.59 and 5.39 per 1000 participant-years, respectively, in people with CRP ≥2mg/L. Analyses stratified by disease type, or number of comorbidities, showed consistent associations between elevated CRP and infection death.

Limitations

Our observational study design precludes assessment of causality. We lacked data on the use of anti-inflammatory therapies after study recruitment.

Conclusion

Low grade inflammation, irrespective of associated comorbidity, identifies people at particularly increased risk of infection death. Decisions to use anti-inflammatory therapies guided by low grade inflammation require careful consideration of the associated risks and benefits.
Ad26.COV2.S breakthrough infections induce high titers of neutralizing antibodies against Omicron and other SARS-CoV-2 variants of concern
Authors: Kitchin Dale , Richardson Simone I. , van der Mescht Mieke A. , Motlou Thopisang , Mzindle Nonkululeko , Moyo-Gwete Thandeka , Makhado Zanele , Ayres Frances , Manamela Nelia P. , Spencer Holly , Lambson Bronwen , Oosthuysen Brent , Kaldine Haajira , du Pisanie Marizane , Mennen Mathilda , Skelem Sango , Williams Noleen , Ntusi Ntobeko A.B. , Burgers Wendy A. , Gray Glenda G. , Bekker Linda-Gail , Boswell Michael T. , Rossouw Theresa M. , Ueckermann Veronica , Moore Penny L.
Published: November 2021

The Janssen (Johnson & Johnson) Ad26.COV2.S non-replicating viral vector vaccine has been widely deployed for COVID-19 vaccination programs in resource-limited settings. Here we confirm that neutralizing and binding responses to Ad26.COV2.S vaccination are stable for 6 months post-vaccination, when tested against multiple SARS-CoV-2 variants. Secondly, using longitudinal samples from individuals who experienced clinically mild breakthrough infections 4 to 5 months after vaccination, we show dramatically boosted binding antibodies, Fc effector function and neutralization. These high titer responses are of similar magnitude to humoral immune responses measured in severely ill, hospitalized donors, and are cross-reactive against diverse SARS-CoV-2 variants, including the extremely neutralization resistant Omicron (B.1.1.529) variant that currently dominates global infections, as well as SARS-CoV-1. These data have implications for population immunity in areas where the Ad26.COV2.S vaccine has been widely deployed, but where ongoing infections continue to occur at high levels.
Atypical action updating in a dynamic environment associated with adolescent obsessive-compulsive disorder
Authors: Marzuki Aleya A. , Vaghi Matilde M. , Conway-Morris Anna , Kaser Muzaffer , Sule Akeem , Apergis-Schoute Annemieke , Sahakian Barbara J. , Robbins Trevor W.
Published: November 2021

Background

Computational research had determined that adults with obsessive-compulsive disorder (OCD) display heightened action updating in response to noise in the environment and neglect meta-cognitive information (such as confidence) when making decisions. These features are proposed to underlie patients’ compulsions despite knowledge they are irrational. Nonetheless, it is unclear whether this extends to adolescents with OCD as research in this population is lacking. Thus, this study aimed to investigate the interplay between action and confidence in adolescents with OCD.

Methods

Twenty-seven adolescents with OCD and 46 controls completed a predictive-inference task, designed to probe how subjects’ actions and confidence ratings fluctuate in response to unexpected outcomes. We investigated how subjects update actions in response to prediction errors (indexing mismatches between expectations and outcomes) and used parameters from a Bayesian model to predict how confidence and action evolve over time. Confidence-action association strength was assessed using a regression model. We also investigated the effects of serotonergic medication.

Results

Adolescents with OCD showed significantly increased learning rates, particularly following small prediction errors. Results were driven primarily by unmedicated patients. Confidence ratings appeared equivalent between groups, although model-based analysis revealed that patients’ confidence was less affected by prediction errors compared to controls. Patients and controls did not differ in the extent to which they updated actions and confidence in tandem.

Conclusions

Adolescents with OCD showed enhanced action adjustments, especially in the face of small prediction errors, consistent with previous research establishing ‘just-right’ compulsions, enhanced error-related negativity, and greater decision-uncertainty in paediatric-OCD. These tendencies were ameliorated in patients receiving serotonergic medication, emphasising the importance of early intervention in preventing disorder-related cognitive deficits. Confidence ratings were equivalent between young patients and controls, mirroring findings in adults OCD research.