bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid-turn inflation in supergravity is rare and tachyonic
Authors: Aragam Vikas , Chiovoloni Roberta , Paban Sonia , Rosati Robert , Zavala Ivonne
Published: March 2022

Strongly non-geodesic, or rapidly turning trajectories in multifield inflation have attracted much interest recently from both theoretical and phenomenological perspectives. Most models with large turning rates in the literature are formulated as effective field theories. In this paper we investigate rapid-turn inflation in supergravity as a first step towards understanding them in string theory. We find that large turning rates can be generated in a wide class of models, at the cost of high field space curvature. In these models, while the inflationary trajectories are stable, one Hessian eigenvalue is always tachyonic and large, in Hubble units. Thus, these models satisfy the de Sitter swampland conjecture along the inflationary trajectory. However, the high curvatures underscore the difficulty of obtaining rapid-turn inflation in realistic string-theoretical models.
In passing, we revisit the η-problem in multifield slow-roll inflation and show that it does not arise, inasmuch as the inflatons, ϕi
, can all be heavier (in absolute value) that the Hubble scale: |mi
|/H>1, ∀i.
The Near-infrared Imager and Slitless Spectrograph for the James Webb Space Telescope. II. Wide Field Slitless Spectroscopy
Authors: Willott Chris J. , Doyon René , Albert Loic , Brammer Gabriel B. , Dixon William V. , Muzic Koraljka , Ravindranath Swara , Scholz Aleks , Abraham Roberto , Artigau Étienne , Bradač Maruša , Goudfrooij Paul , Hutchings John B. , Iyer Kartheik G. , Jayawardhana Ray , LaMassa Stephanie , Martis Nicholas , Meyer Michael R. , Morishita Takahiro , Mowla Lamiya , Muzzin Adam , Noirot Gaël , Pacifici Camilla , Rowlands Neil , Sarrouh Ghassan , Sawicki Marcin , Taylor Joanna M. , Volk Kevin , Zabl Johannes
Published: March 2022

We present the wide field slitless spectroscopy mode of the NIRISS instrument on the James Webb Space Telescope. This mode employs two orthogonal low-resolution (resolving power ≈150) grisms in combination with a set of six blocking filters in the wavelength range 0.8–2.3 μm to provide a spectrum of almost every source across the field-of-view. When combined with the low background, high sensitivity and high spatial resolution afforded by the telescope, this mode will enable unprecedented studies of the structure and evolution of distant galaxies. We describe the performance of the as-built hardware relevant to this mode and expected imaging and spectroscopic sensitivity. We discuss operational and calibration procedures to obtain the highest quality data. As examples of the observing mode usage, we present details of two planned Guaranteed Time Observations programs: The Canadian NIRISS Unbiased Cluster Survey and The NIRISS Survey for Young Brown Dwarfs and Rogue Planets.
The role of pickup truck electrification in the decarbonization of light-duty vehicles
Authors: Woody Maxwell , Vaishnav Parth , Keoleian Gregory A , De Kleine Robert , Kim Hyung Chul , Anderson James E , Wallington Timothy J
Published: March 2022

Electrification can reduce the greenhouse gas (GHG) emissions of light-duty vehicles. Previous studies have focused on comparing battery electric vehicle (BEV) sedans to their conventional internal combustion engine vehicle (ICEV) or hybrid electric vehicle (HEV) counterparts. We extend the analysis to different vehicle classes by conducting a cradle-to-grave life cycle GHG assessment of model year 2020 ICEV, HEV, and BEV sedans, sports utility vehicles (SUVs), and pickup trucks in the United States. We show that the proportional emissions benefit of electrification is approximately independent of vehicle class. For sedans, SUVs, and pickup trucks we find HEVs and BEVs have approximately 28% and 64% lower cradle-to-grave life cycle emissions, respectively, than ICEVs in our base case model. This results in a lifetime BEV over ICEV GHG emissions benefit of approximately 45 tonnes CO2e for sedans, 56 tonnes CO2e for SUVs, and 74 tonnes CO2e for pickup trucks. The benefits of electrification remain significant with increased battery size, reduced BEV lifetime, and across a variety of drive cycles and decarbonization scenarios. However, there is substantial variation in emissions based on where and when a vehicle is charged and operated, due to the impact of ambient temperature on fuel economy and the spatiotemporal variability in grid carbon intensity across the United States. Regionally, BEV pickup GHG emissions are 13%–118% of their ICEV counterparts and 14%–134% of their HEV counterparts across U.S. counties. BEVs have lower GHG emissions than HEVs in 95%–96% of counties and lower GHG emissions than ICEVs in 98%–99% of counties. As consumers migrate from ICEVs and HEVs to BEVs, accounting for these spatiotemporal factors and the wide range of available vehicle classes is an important consideration for electric vehicle deployment, operation, policymaking, and planning.
Comparison of FDA Table of Pharmacogenetic Associations and Clinical Pharmacogenetics Implementation Consortium guidelines
Authors: Pritchard Daryl , Patel Jai N , Stephens Lindsay E , McLeod Howard L
Published: March 2022

Purpose

Healthcare professionals need a clear understanding of information about gene-drug interactions in order to make optimal use of pharmacogenetic (PGx) testing. In this report, we compare PGx information in the US Food and Drug Administration (FDA) Table of Pharmacogenetic Associations with information presented in Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines.

Information from CPIC guidelines and the FDA Table of Pharmacogenetic Associations do not have a high level of concordance. Many drugs mentioned in CPIC guidelines are not listed in the FDA table and vice versa, and the same gene-drug association and dosing recommendation was reported for only 5 of the 126 drugs included in either source. Furthermore, classification of drugs in specific sections of the FDA table does not correlate well with CPIC-assigned or provisionally assigned clinical actionability levels. The Pharmacogenomics Knowledge Base (PharmGKB) clinical annotation levels are generally high for drugs mentioned in CPIC guidelines. PharmGKB clinical annotation levels are often unassigned or are lower level for drugs listed on the FDA table but not in CPIC guidelines. These differences may be due in part to FDA having access to PGx information that is unavailable in published literature and/or because PGx classifications are based on criteria other than clinical actionability.

Conclusion

There are important differences between the PGx information presented in the FDA Table of Pharmacogenetic Associations and in CPIC guidelines. FDA and CPIC have different perspectives when evaluating PGx associations and use different approaches and information resources when considering clinical validity related to specific medicines. Understanding how information sources developed by each group differ and can be used together to form a holistic view of PGx may be helpful in increasing adoption of these information sources in practice.
A Meta-Regression of Trial Features Predicting the Effects of Alcohol Use Disorder Pharmacotherapies on Drinking Outcomes in Randomized Clinical Trials: A Secondary Data Analysis
Authors: Grodin Erica N , Donato Suzanna , Du Han , Green ReJoyce , Bujarski Spencer , Ray Lara A
Published: February 2022

Aims

To test whether two critical design features, inclusion criteria of required pre-trial abstinence and pre-trial alcohol use disorder (AUD) diagnosis, predict the likelihood of detecting treatment effects in AUD pharmacotherapy trials.

Methods

This secondary data analysis used data collected from a literature review to identify randomized controlled pharmacotherapy trials for AUD. Treatment outcomes were selected into abstinence and no heavy drinking. Target effect sizes were calculated for each outcome and a meta-regression was conducted to test the effects of required pre-trial abstinence, required pre-trial AUD diagnosis, and their interaction on effect sizes. A sub-analysis was conducted on trials, which included FDA-approved medications for AUD.

Results

In total, 118 studies testing 19 medications representing 21,032 treated participants were included in the meta-regression analysis. There was no significant effect of either predictor on abstinence or no heavy drinking outcomes in the full analysis or in the sub-study of FDA-approved medications.

Conclusion

By examining these design features in a quantitative, rather than qualitative, fashion the present study advances the literature and shows that requiring AUD diagnosis or requiring pre-trial abstinence do not impact the likelihood of a significant medication effect in the trial.
Complex patterns of ploidy in a holocentric plant clade (Schoenus, Cyperaceae) in the Cape biodiversity hotspot
Authors: Elliott Tammy L , Muasya A Muthama , Bureš Petr
Published: February 2022

Background and Aims

It is unclear how widespread polyploidy is throughout the largest holocentric plant family – the Cyperaceae. Because of the prevalence of chromosomal fusions and fissions, which affect chromosome number but not genome size, it can be impossible to distinguish if individual plants are polyploids in holocentric lineages based on chromosome count data alone. Furthermore, it is unclear how differences in genome size and ploidy levels relate to environmental correlates within holocentric lineages, such as the Cyperaceae.

Methods

We focus our analyses on tribe Schoeneae, and more specifically the southern African clade of Schoenus. We examine broad-scale patterns of genome size evolution in tribe Schoeneae and focus more intensely on determining the prevalence of polyploidy across the southern African Schoenus by inferring ploidy level with the program ChromEvol, as well as interpreting chromosome number and genome size data. We further investigate whether there are relationships between genome size/ploidy level and environmental variables across the nutrient-poor and summer-arid Cape biodiversity hotspot.

Key Results

Our results show a large increase in genome size, but not chromosome number, within Schoenus compared to other species in tribe Schoeneae. Across Schoenus, there is a positive relationship between chromosome number and genome size, and our results suggest that polyploidy is a relatively common process throughout the southern African Schoenus. At the regional scale of the Cape, we show that polyploids are more often associated with drier locations that have more variation in precipitation between dry and wet months, but these results are sensitive to the classification of ploidy level.

Conclusions

Polyploidy is relatively common in the southern African Schoenus, where a positive relationship is observed between chromosome number and genome size. Thus, there may be a high incidence of polyploidy in holocentric plants, whose cell division properties differ from monocentrics.
Maize brace root mechanics vary by whorl, genotype and reproductive stage
Authors: Hostetler Ashley N , Erndwein Lindsay , Ganji Elahe , Reneau Jonathan W , Killian Megan L , Sparks Erin E
Published: March 2022

Background and Aims

Root lodging is responsible for significant crop losses worldwide. During root lodging, roots fail by breaking, buckling or pulling out of the ground. In maize, above-ground roots, called brace roots, have been shown to reduce susceptibility to root lodging. However, the underlying structural–functional properties of brace roots that prevent root lodging are poorly defined. In this study, we quantified structural mechanical properties, geometry and bending moduli for brace roots from different whorls, genotypes and reproductive stages.

Methods

Using 3-point bend tests, we show that brace root mechanics are variable by whorl, genotype and reproductive stage.

Key Results

Generally, we find that within each genotype and reproductive stage, the brace roots from the first whorl (closest to the ground) had higher structural mechanical properties and a lower bending modulus than brace roots from the second whorl. There was additional variation between genotypes and reproductive stages. Specifically, genotypes with higher structural mechanical properties also had a higher bending modulus, and senesced brace roots had lower structural mechanical properties than hydrated brace roots.

Conclusions

Collectively these results highlight the importance of considering whorl-of-origin, genotype and reproductive stage for the quantification of brace root mechanics, which is important for mitigating crop loss due to root mechanical failure.
Systematic optimization of host-directed therapeutic targets and preclinical validation of repositioned antiviral drugs
Authors: Xie Dafei , He Song , Han Lu , Wu Lianlian , Huang Hai , Tao Huan , Zhou Pingkun , Shi Xunlong , Bai Hui , Bo Xiaochen
Published: February 2022

Inhibition of host protein functions using established drugs produces a promising antiviral effect with excellent safety profiles, decreased incidence of resistant variants and favorable balance of costs and risks. Genomic methods have produced a large number of robust host factors, providing candidates for identification of antiviral drug targets. However, there is a lack of global perspectives and systematic prioritization of known virus-targeted host proteins (VTHPs) and drug targets. There is also a need for host-directed repositioned antivirals. Here, we integrated 6140 VTHPs and grouped viral infection modes from a new perspective of enriched pathways of VTHPs. Clarifying the superiority of nonessential membrane and hub VTHPs as potential ideal targets for repositioned antivirals, we proposed 543 candidate VTHPs. We then presented a large-scale drug–virus network (DVN) based on matching these VTHPs and drug targets. We predicted possible indications for 703 approved drugs against 35 viruses and explored their potential as broad-spectrum antivirals. In vitro and in vivo tests validated the efficacy of bosutinib, maraviroc and dextromethorphan against human herpesvirus 1 (HHV-1), hepatitis B virus (HBV) and influenza A virus (IAV). Their drug synergy with clinically used antivirals was evaluated and confirmed. The results proved that low-dose dextromethorphan is better than high-dose in both single and combined treatments. This study provides a comprehensive landscape and optimization strategy for druggable VTHPs, constructing an innovative and potent pipeline to discover novel antiviral host proteins and repositioned drugs, which may facilitate their delivery to clinical application in translational medicine to combat fatal and spreading viral infections.
Sex-specific effects of bisphenol A on the signaling pathway of ESRRG in the human placenta
Authors: Zou Zhiyong , Harris Lynda K , Forbes Karen , Heazell Alexander E P
Published: February 2022

Bisphenol A (BPA) exposure during pregnancy is associated with low fetal weight, particularly in male fetuses. The expression of estrogen-related receptor gamma (ESRRG), a receptor for BPA in the human placenta, is reduced in fetal growth restriction. This study sought to explore whether ESRRG signaling mediates BPA-induced placental dysfunction and determine whether changes in the ESRRG signaling pathway are sex-specific. Placental villous explants from 18 normal term pregnancies were cultured with a range of BPA concentrations (1 nM–1 μM). Baseline BPA concentrations in the placental tissue used for explant culture ranged from 0.04 to 5.1 nM (average 2.3 ±1.9 nM; n = 6). Expression of ESRRG signaling pathway constituents and cell turnover were quantified. BPA (1 μM) increased ESRRG mRNA expression after 24 h in both sexes. ESRRG mRNA and protein expression was increased in female placentas treated with 1 μM BPA for 24 h but was decreased in male placentas treated with 1 nM or 1 μM for 48 h. Levels of 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1) and placenta specific-1 (PLAC1), genes downstream of ESRRG, were also affected. HSD17B1 mRNA expression was increased in female placentas by 1 μM BPA; however, 1 nM BPA reduced HSD17B1 and PLAC1 expression in male placentas at 48 h. BPA treatment did not affect rates of proliferation, apoptosis, or syncytiotrophoblast differentiation in cultured villous explants. This study has demonstrated that BPA affects the ESRRG signaling pathway in a sex-specific manner in human placentas and a possible biological mechanism to explain the differential effects of BPA exposure on male and female fetuses observed in epidemiological studies.
Global variations in the definition and management of multifocal and multicentric breast cancer: the MINIM international survey
Authors: Masannat Yazan A , Rocco Nicola , Garreffa Emanuele , Gulluoglu Bahadir M , Kothari Ashutosh , Maglia Anna , Nava Maurizio B , Omar Omar S , Potter Shelley , Catanuto Giuseppe
Published: February 2022

The aim of this survey was to understand variation in the definition and management of multifocal and multicentric breast cancer globally. Some 743 physicians from 100 countries responded to this survey, which has provided a clear snapshot of international practice that can inform future work in this area. There is variation in the definition and management of multifocal/multicentric breast cancer among the international breast surgical community, the most controversial aspect being the use of MRI.
TNFα antagonist in combination with PD-1 blocker to prevent or retard malignant transformation of B[a]P-induced chronic lung inflammation
Authors: Zhao Ai , Li Fanfan , Wei Cheng , Zhou Zhujun , Luo Xianqiang , Wu Haiming , Ning Chunhong , Liu Wanyu , Li Dong , Lin Danni , Liu Shuwen , Zhang Guangji , Gao Jimin
Published: March 2022

Benzo[a]pyrene (B[a]P) is a typical complete carcinogen in tobacco, but its mechanism of inducing the development of chronic pneumonia and consequent lung cancer is unclear. Here we elucidated the role of myeloid-derived suppressor cells (MDSCs) in developing B[a]P-induced chronic lung inflammation and efficacy of immunotherapy in preventing subsequent malignant transformation. Our study showed that as B[a]P could induce the accumulation of MDSCs in lung tissues and enhance the immunosuppressive effect regulated by cytokines and metabolites, thereby promoting the formation of immunosuppressive microenvironment, where effector T cells were exhausted, NK cells were dysfunctional, regulatory T (Treg) cells were expanded, polarized alveolar macrophages were transformed from M1 to M2. Subsequently, we performed the immunotherapy to block TNFɑ only or both TNFɑ and PD-1 at the early- or middle-stage of B[a]P-induced chronic lung inflammation to ameliorate the immunosuppressive microenvironment. We found that TNFɑ antagonist alone or with PD-1 blocker was shown to exert therapeutic effects on malignant transformation at the early stage of B[a]P-induced chronic lung inflammation. Taken together, our findings demonstrated that B[a]P-induced chronic lung inflammation resulted in the accumulation of MDSCs in lung tissues and exercise their immunosuppressive functions, thereby developing an immunosuppressive microenvironment, thus TNFɑ antagonist alone or with PD-1 blocker could prevent or retard the malignant transformation of B[a]P-induced chronic lung inflammation.
Prediction and action in cortical pain processing
Authors: Koppel Lina , Novembre Giovanni , Kämpe Robin , Savallampi Mattias , Morrison India
Published: March 2022

Predicting that a stimulus is painful facilitates action to avoid harm. But how distinct are the neural processes underlying the prediction of upcoming painful events vis-à-vis those taking action to avoid them? Here, we investigated brain activity as a function of current and predicted painful or nonpainful thermal stimulation, as well as the ability of voluntary action to affect the duration of upcoming stimulation. Participants performed a task which involved the administration of a painful or nonpainful stimulus (S1), which predicted an immediately subsequent very painful or nonpainful stimulus (S2). Pressing a response button within a specified time window during S1 either reduced or did not reduce the duration of the upcoming stimulation. Predicted pain increased activation in several regions, including anterior cingulate cortex (ACC), midcingulate cortex (MCC), and insula; however, activation in ACC and MCC depended on whether a meaningful action was performed, with MCC activation showing a direct relationship with motor output. Insula’s responses for predicted pain were also modulated by potential action consequences, albeit without a direct relationship with motor output. These findings suggest that cortical pain processing is not specifically tied to the sensory stimulus, but instead, depends on the consequences of that stimulus for sensorimotor control of behavior.
Prematurity, Delivery Method, and Infant Feeding Type Are Not Associated with Paediatric-onset Inflammatory Bowel Disease Risk: A Scottish Retrospective Birth Cohort Study
Authors: Burgess Christopher J , Schnier Christian , Wood Rachael , Henderson Paul , Wilson David C
Published: March 2022

Background and Aims

The incidence of paediatric-onset inflammatory bowel disease [PIBD] continues to rise globally. We aimed to determine whether mode of delivery, gestational age at birth, or type of infant feeding contribute to the development of PIBD in a nationwide cohort of Scottish children.

Methods

All children born in Scotland between 1981 and 2017 were identified using linked health administrative data to determine mode of delivery, gestational age at birth, and type of infant feeding. PIBD cases were defined as onset of Crohn’s disease [CD], ulcerative colitis [UC], or IBD-unclassified [IBDU] before age 16 years. Validation was performed within an entire Scottish health board [16% of total population] via individual case-note verification. Hazard ratios [HR] were calculated for each exposure using Cox proportional hazards models.

Results

A study population of 2 013 851 children was identified including 1721 PIBD cases. Validation of 261 PIBD patients coded as CD and/or UC identified 242 [93%] as true positive. Children delivered vaginally did not have an altered risk of developing PIBD compared with those delivered by caesarean section, adjusted HR 0.95 [95% CI 0.84-1.08] [p = 0.46]. Compared with children born at term [≥37 weeks], children born prematurely did not have an altered risk of developing PIBD, i.e., at 24-31 weeks of gestation, HR 0.99 [95% CI 0.57-1.71] [p = 0.97] and at 32-36 weeks of gestation, HR 0.96 [95% CI 0.76-1.20] [p = 0.71]. Compared with children exclusively breastfed at age 6 weeks, children exclusively formula fed did not have an altered risk of developing PIBD: adjusted HR 0.97 [95% CI 0.81-1.15] [p = 0.69].

Conclusions

This population-based study demonstrates no association between mode of delivery, gestational age, or exclusive formula feeding at 6 weeks, and the development of PIBD.
Open surgical replacement of the descending thoracic and thoracoabdominal aorta in patients with confirmed Marfan and Loeys-Dietz syndromes: A 20-year single-centre experience
Authors: Adam Donald , Iafrancesco Mauro , Juszczak Maciej , Claridge Martin , Quinn David , Senanayake Eshan , Clift Paul , Mascaro Jorge
Published: February 2022

OBJECTIVES

A relatively small proportion of patients with heritable thoracic aortic disease require open surgical replacement of the distal thoracic aorta. We reviewed the outcome in patients with Marfan and Loeys-Dietz syndromes treated in an aortic centre in the United Kingdom.

METHODS

We performed a single-centre retrospective study of consecutive patients treated between October 1999 and December 2019. The primary end point was 30-day mortality. Secondary end points were Kaplan–Meier estimates of medium-term survival and freedom from distal reintervention. Data are presented as median (interquartile range).

RESULTS

A total of 58 patients [33 men; 51 with Marfan syndrome; median age 41 years (35–48); median aneurysm diameter 60 mm (55–74)] underwent open descending (n = 21) or thoracoabdominal aortic replacement (n = 37). All repairs were performed using cardiopulmonary bypass with hypothermic circulatory arrest in 31 patients. The 30-day mortality was 5.2% (n = 3, including 2 patients ≥ 60 years with significant comorbidity). Major non-fatal complications included early reoperation (n = 7), tracheostomy (n = 9), temporary renal replacement therapy (n = 3), permanent spinal cord deficit (n = 2) and permanent stroke (n = 1). Median follow-up was 81 months (48–127). Estimated (±standard error) 5-year survival was 85% ±5%. Seven patients had distal aortic reintervention with no deaths or spinal cord deficit: estimated 5-year freedom from distal reintervention was 94% ±3%. There was no difference in survival or freedom from distal reintervention comparing: elective vs. non-elective; type of heritable thoracic aortic disease; DeBakey type; or extent of surgical repair.

CONCLUSIONS

Descending thoracic and thoracoabdominal aortic replacement in patients with heritable thoracic aortic disease can be performed with low perioperative morbidity and mortality, satisfactory long-term survival and low requirement for distal reintervention.
Cerebral desaturation during neonatal congenital heart surgery is associated with perioperative brain structure alterations but not with neurodevelopmental outcome at 1 year
Authors: De Silvestro Alexandra A , Krüger Bernard , Steger Céline , Feldmann Maria , Payette Kelly , Krüger Julia , Kottke Raimund , Hagmann Cornelia , Bosshart Marco , Bürki Christoph , Dave Hitendu , Tuura Ruth , Latal Beatrice , Jakab András , Knirsch Walter
Published: February 2022

OBJECTIVES

The significance of intraoperative cerebral desaturation (CD) measured by near-infrared spectroscopy (NIRS) to predict neurological outcome after congenital heart surgery is uncertain. The goal of this study was to compare brain structure changes and neurodevelopmental outcome in patients with severe congenital heart disease with and without intraoperative CD.

METHODS

Neonates requiring congenital heart surgery were enrolled in a cohort study. NIRS data from their first cardiac operation were collected. Pre- and postoperative brain magnetic resonance imaging results and Bayley-III scores at 1 year were compared between patients with and without CD, defined by 2 NIRS thresholds: regional cerebral oxygen saturation (rSO2) of 45% (45%rSO2) and rSO2 below 20% of baseline value (20%BLrSO2).

RESULTS

Thirty-two patients (72% male) with d-transposition of the great arteries (n = 24, 75%) and other complex types of congenital heart diseases (n = 8, 25%) were analysed. Perioperative relative lateral ventricle volume change was increased in patients with versus without intraoperative CD (P = 0.003 for 45%rSO2, P = 0.008 for 20%BLrSO2). For 45%rSO2, the effect of CD remained significant after adjusting for age at postoperative scan, time between scans and cardiac diagnosis (P = 0.019). New intracranial lesions occurred predominantly in CD groups (6/6 patients for 45%rSO2, 5/6 patients for 20%BLrSO2). Neurodevelopmental outcome at 1 year was not associated with intraoperative CD.

CONCLUSIONS

This study demonstrates the clinical relevance of NIRS monitoring during congenital heart surgery. The occurrence of intraoperative CD is associated with perioperative lateral ventricle volume change and new intracranial lesions.
Composition and functioning of the soil microbiome in the highest altitudes of the Italian Alps and potential effects of climate change
Authors: D'Alò Federica , Baldrian Petr , Odriozola Iñaki , Morais Daniel , Větrovský Tomáš , Zucconi Laura , Ripa Caterina , Cannone Nicoletta , Malfasi Francesco , Onofri Silvano
Published: March 2022

As the European Alps are experiencing a strong climate warming, this study analyzed the soil microbiome at different altitudes and among different vegetation types at the Stelvio Pass (Italian Alps), aiming to (i) characterize the composition and functional potential of the microbiome of soils and their gene expression during the peak vegetative stage; (ii) explore the potential short-term (using open-top chambers) and long-term (space-for-time substitutions) effects of increasing temperature on the alpine soil microbiome. We found that the functional potential of the soil microbiome and its expression differed among vegetation types. Microbial α-diversity increased along the altitudinal gradient. At lower altitude, shrubland had the highest proportion of fungi, which was correlated with higher amounts of CAZymes, specific for degrading fungal biomass and recalcitrant plant biopolymers. Subalpine upward vegetation shift could lead a possible loss of species of alpine soils. Shrub encroachment may accelerate higher recalcitrant C decomposition and reduce total ecosystem C storage, increasing the efflux of CO2 to the atmosphere with a positive feedback to warming. A total of 5 years of warming had no effect on the composition and functioning of microbial communities, indicating that longer-term warming experiments are needed to investigate the effects of temperature increases on the soil microbiome.
Large Contribution of Oral Status for Death Among Modifiable Risk Factors in Older Adults: The Japan Gerontological Evaluation Study (JAGES) Prospective Cohort Study
Authors: Nakazawa Noriko , Kusama Taro , Cooray Upul , Yamamoto Takafumi , Kiuchi Sakura , Abbas Hazem , Yamamoto Tatsuo , Kondo Katsunori , Osaka Ken , Aida Jun
Published: March 2022

Background

Oral diseases are preventable and modifiable, but highly prevalent, and cause worse oral status. Particularly, tooth loss has increased in aging societies. However, studies on population-attributable risks of modifiable risk factors for mortality have neglected oral status. This study aimed to investigate the impact of modifiable risk factors on mortality, including oral status.

Methods

This cohort study used the Japan Gerontological Evaluation Study data, including participants aged ≥65 years. The outcome was death between August 2010 and March 2017. We calculated the hazard ratios (HRs) and population attributable fraction (PAF) of modifiable risk factors (oral status, hypertension, depression, heart disease, diabetes, physical activity, smoking status, and alcohol drinking history) for mortality.

Results

Analyses included 24 175 men and 27 888 women (mean age: 73.8 [6.0] and 74.2 [6.1], respectively). In men, after adjusting for covariates, having no teeth showed the highest hazard ratio (HR = 1.67, 95% confidence interval [CI] = 1.51–1.86) among the modifiable risk factors, and the PAF for the number of teeth (18.2%) was the second largest following age. In women, having no teeth had the third largest HR (HR = 1.37, 95% CI = 1.19–1.56) following current and former smoking. The PAF for the number of teeth (8.5%) was the sixth largest, which was larger than that of smoking status (4.8%).

Conclusions

In the older population, the HR and PAF of the number of teeth on mortality were sufficiently large compared with other modifiable risk factors, especially in men. Therefore, maintaining good oral status should be included more in global health policies.
Promoting Resilience and Flourishing Among Older Adult Residents in Community Living: A Feasibility Study
Authors: Traeger Lara , Styklunas Grace M , Park Ellen Y , Lee Matthew T , Fricchione Gregory , Park Elyse R
Published: March 2022

Background and Objectives

The Stress Management and Relaxation Training—Relaxation Response Resiliency Program (SMART-3RP) is a mind–body group intervention that integrates relaxation training with cognitive behavioral and positive psychology techniques. This study assessed SMART-3RP feasibility, acceptability, and preliminary efficacy for enhancing resilience and flourishing among older adults in continuing care retirement communities (CCRCs).

Research Design and Methods

We conducted a prospective single-arm study of SMART-3RP groups delivered by clinicians at 4 CCRCs (n = 80). Eligible residents lived in community apartments. Participants completed pre- and postintervention surveys. We evaluated attendance (hypothesis: ≥60% attend ≥6 of 9 sessions), enrollment, and retention. Mixed methods were used to explore acceptability. Paired samples t-tests were conducted to explore changes in resilience, flourishing, and key intervention targets.

Results

From March to June 2021, we screened 89 residents with 87 (98%) consenting to participate and 80 (90%) enrolling in the study. Among 80 participants (85% female; 98% non-Hispanic White; M age = 80 years [SD = 6]), 88% attended ≥6 sessions, and 89% completed the postintervention survey. Participants found meaning in participation and practiced skills in the context of challenges such as caregiving burden or bereavement. Survey results, showing increases in resilience, flourishing, and several intervention targets, aligned with participants’ perceived intervention value.

Discussion and Implications

SMART-3RP was feasible and acceptable for CCRC residents; participants perceived value in practicing mind–body strategies in a group-based setting. Preliminary evidence suggested a pattern of improvements in resilience, flourishing, and intervention targets. Findings provide insights for mind–body interventions and recommendations for adaptations to late-in-life concerns and community settings.

Clinical Trials Registration Number

NCT04720014
The Impact of Changing Social Support on Older Persons’ Onset of Loneliness During the COVID-19 Pandemic in the United Kingdom
Authors: Vlachantoni Athina , Evandrou Maria , Falkingham Jane , Qin Min
Published: March 2022

Background and Objectives

Social distancing measures aimed at controlling the spread of coronavirus disease 2019 (COVID-19) are likely to have increased social isolation among those older than 70 instructed to shield at home. This study examines the incidence of loneliness by gender over the first 10 months of the COVID-19 pandemic among persons aged 70 and older in the United Kingdom, and the impact of changing social networks and perceived social support on the new occurrence of loneliness.

Research Design and Methods

Participants (N = 1,235) aged 70 and older with no reports of loneliness before the pandemic who participated in 7 rounds of the Understanding Society: COVID-19 Study (April 2020–January 2021) and the main Understanding Society Study conducted during 2019. Cox regression analyzed the time to a new occurrence of loneliness.

Results

Among older people who hardly ever/never felt lonely before the pandemic, 33.7% reported some degree of loneliness between April 2020 and January 2021. Living in a single-person household, having received more social support before the pandemic, changes in support receipt during the pandemic, and a deteriorating relationship with one’s partner during the pandemic increased the risk of experiencing loneliness. Older women were more likely than older men to report loneliness, even when living with a partner.

Discussion and Implications

During the 3 COVID-19-related lockdowns in the United Kingdom, changes in older people’s social networks and support resulted in a significant onset of loneliness. Findings highlight the risks of shielding older persons from COVID-19 in terms of their mental well-being and the importance of strengthening intergenerational support.
FastLink: a machine learning and GPU-based fast phase association method and its application to Yangbi Ms 6.4 aftershock sequences
Authors: Yu Ziye , Wang Weitao
Published: February 2022

The development of sensitive automatic phase picking method can produce P/S phase picks for lots of seismic stations quickly. This raises the requirement for fast phase association method to group phase picks into candidate events. Here we present FastLink, a machine learning and GPU based phase associator, to group phase picks efficiently. FastLink is designed to utilize parallel computing power of GPU, it uses a 3-layer neural network to determine valid picks and the non-maximum suppression (NMS) algorithm to distinguish the events simultaneously occurred in different places. With the aid of GPU, FastLink can perform faster grid search than traditional methods. We apply FastLink to aftershock sequences identification of the Yangbi Ms 6.4 earthquake occurred on 21 May 2021, in Yunnan Province, China. Over 17 000 events are successfully associated using about 2 million picks from 1-week records of 79 stations surrounding the main shock. Over 93.5 per cent of the ML ≥ 0 events in the manual verified bulletin ML are successfully associated by FastLink. Compared with the widely used REAL method, FastLink produces comparable results and is over 12 times faster with GPU acceleration. This shows its potential for processing a large number of phase picks quickly.
A new broad-band ocean bottom seismograph and characteristics of the seismic ambient noise on the South China Sea seafloor based on its recordings
Authors: Wang Yizhi , Yang Ting , Wu Yuechu , Liu Dan , Huang Xinfeng , Wang Jun , Zhong Weixing , Shou Haitao , Zhou Yong , Chen Yongshun
Published: March 2022

The ocean is the primary source of seismic ambient noise. Therefore, seismic recordings at seafloor stations should reveal noise characteristics more directly than land stations. However, due to a lack of broad-band seismic instrumentation, seafloor noise studies using seafloor stations have been inadequate compared to land-based instrumentation. In this study, we use seismic data collected at the South China Sea (SCS) seafloor by newly developed ocean bottom seismographs (OBSs) to analyze the ambient noise features in this marginal sea. The broad-band OBS, dubbed ‘Pankun’, has unique shielding to isolate its sensor from the influences of bottom currents. A side-by-side land test between the OBS sensor unit and a standalone seismometer showed that the self-noise caused by the gimbal and the pressure case is insignificant. The recordings on the SCS seafloor have distinct noise spectra. The double frequency microseisms (DFMs) have a single instead of double peak like that seen for Pacific stations. The peak appears in a lower period range (1–5 s) than in the global noise model, indicating that the primary source region for the DFM is the SCS itself. The high-frequency content of the DFM is attenuated more as it propagates from its source region (seafloor) to land stations. The single frequency microseism (SFM) peak on the spectrum is weak, reflecting that SFMs, generated in shallow water along the coast, have difficulties propagating back into the deep ocean due to the substantial increase in seafloor depth. A long-period Earth's hum signal is also identifiable on the vertical component at periods greater than 50 s, probably due to the anti-current design of the OBS. Although the seasonal sea state mainly affects the noise level, extreme events such as typhoons can produce short-term abnormally high DFMs in the basin. However, the DFM highs caused by such events exhibit complex patterns, depending on the wind speed, duration, and area covered by the events.
De novo variants in EMC1 lead to neurodevelopmental delay and cerebellar degeneration and affect glial function in Drosophila
Authors: Chung Hyung-Lok , Rump Patrick , Lu Di , Glassford Megan R , Mok Jung-Wan , Fatih Jawid , Basal Adily , Marcogliese Paul C , Kanca Oguz , Rapp Michele , Fock Johanna M , Kamsteeg Erik-Jan , Lupski James R , Larson Austin , Haninbal Mark C , Bellen Hugo , Harel Tamar
Published: March 2022

Background

The endoplasmic reticulum (ER)-membrane protein complex (EMC) is a multi-protein transmembrane complex composed of 10 subunits that functions as a membrane-protein chaperone. Variants in EMC1 lead to neurodevelopmental delay and cerebellar degeneration. Multiple families with biallelic variants have been published, yet to date, only a single report of a monoallelic variant has been described, and functional evidence is sparse.

Methods

Exome sequencing was used to investigate the genetic cause underlying severe developmental delay in three unrelated children. EMC1 variants were modeled in Drosophila, using loss-of-function (LoF) and overexpression studies. Glial-specific and neuronal-specific assays were used to determine whether the dysfunction was specific to one cell type.

Results

Exome sequencing identified de novo variants in EMC1 in three individuals affected by global developmental delay, hypotonia, seizures, visual impairment and cerebellar atrophy. All variants were located at Pro582 or Pro584. Drosophila studies indicated that imbalance of EMC1—either overexpression or knockdown—results in pupal lethality and suggest that the tested homologous variants are LoF alleles. In addition, glia-specific gene dosage, overexpression or knockdown, of EMC1 led to lethality, whereas neuron-specific alterations were tolerated.

Discussion

We establish de novo monoallelic EMC1 variants as causative of a neurological disease trait by providing functional evidence in a Drosophila model. The identified variants failed to rescue the lethality of a null allele. Variations in dosage of the wild-type EMC1, specifically in glia, lead to pupal lethality, which we hypothesize results from the altered stoichiometry of the multi-subunit protein complex EMC.
The need to see a bigger picture to understand the ups and downs of Pacific salmon abundances
Authors: Beamish Richard
Published: March 2022

There are more Pacific salmon in the ocean recently than in recorded history. Increases are believed to be related to shifts in climate but specific, biologically based mechanisms linking climate to increases are not known. At the same time, Pacific salmon abundances in Japan and on Canada's west coast are at historic low levels with attempts to stop the decline unsuccessful. Most juvenile salmon that enter the ocean die, resulting in large abundance increases and decreases from small changes in the already very low ocean survival. Because of this sensitivity to changes in ocean ecosystems and because of the recent basin-scale fluctuations in trends in abundance, I propose that it is time to see a bigger picture and improve the understanding of the biological mechanisms that most influence ocean survival. I leave it to readers to decide if my example of Pacific salmon is part of a more general need in fisheries science to better understand the biological mechanisms linking survival to climate.
A phenome-wide bidirectional Mendelian randomization analysis of atrial fibrillation
Authors: Wang Qin , Richardson Tom G , Sanderson Eleanor , Tudball Matthew J , Ala-Korpela Mika , Davey Smith George , Holmes Michael V
Published: March 2022

Background

The prevalence of atrial fibrillation (AF) is increasing with an aging worldwide population, yet a comprehensive understanding of its causes and consequences remains limited. We aim to assess the causes and consequences of AF via a bidirectional Mendelian randomization (MR) analysis.

Methods

We used publicly available genome-wide association study (GWAS) summary data, centralized and harmonized by an open GWAS database. We assessed the genetically predicted effects of 5048 exposures on risk of AF, and the genetically predicted effects of genetic liability to AF, on 10 308 outcomes via two-sample MR analysis. Multivariable MR analysis was further conducted to explore the comparative roles of identified risk factors.

Results

MR analysis suggested that 55 out of 5048 exposure traits, including four proteins, play a causal role in AF (P <1e-5 allowing for multiple comparisons). Multivariable analysis suggested that higher body mass index, height and systolic blood pressure as well as genetic liability to coronary artery diseases independently cause AF. Three out of the four proteins (DUSP13, TNFSF12 and IL6R) had a drug prioritizing score for atrial fibrillation of 0.26, 0.38 and 0.88, respectively (values closer to 1 indicating stronger evidence of the protein as a potential drug target). Genetic liability to AF was linked to a higher risk of cardio-embolic ischaemic stroke.

Conclusions

Our results suggest body mass index, height, systolic blood pressure and genetic liability to coronary artery disease are independent causal risk factors for AF. Several proteins, including DUSP13, IL-6R and TNFSF12, may have therapeutic potential for AF.
Association between indoor residual spraying and pregnancy outcomes: a quasi-experimental study from Uganda
Authors: Roh Michelle E , Mpimbaza Arthur , Oundo Brenda , Irish Amanda , Murphy Maxwell , Wu Sean L , White Justin S , Shiboski Stephen , Glymour M Maria , Gosling Roly , Dorsey Grant , Sturrock Hugh
Published: March 2022

Background

Malaria is a risk factor for adverse pregnancy outcomes. Indoor residual spraying with insecticide (IRS) reduces malaria infections, yet the effects of IRS on pregnancy outcomes are not well established. We evaluated the impact of a large-scale IRS campaign on pregnancy outcomes in Eastern Uganda.

Methods

Birth records (n = 59 992) were obtained from routine surveillance data at 25 health facilities from five districts that were part of the IRS campaign and six neighbouring control districts ∼27 months before and ∼24 months after the start of the campaign (January 2013-May 2017). Campaign effects on low birthweight (LBW) and stillbirth incidence were estimated using the matrix completion method (MC-NNM), a machine-learning approach to estimating potential outcomes, and compared with the difference-in-differences (DiD) estimator. Subgroup analyses were conducted by HIV and gravidity.

Results

MC-NNM estimates indicated that the campaign was associated with a 33% reduction in LBW incidence: incidence rate ratio (IRR) = 0.67 [95% confidence interval (CI): 0.49–0.93)]. DiD estimates were similar to MC-NNM [IRR = 0.69 (0.47–1.01)], despite a parallel trends violation during the pre-IRS period. The campaign was not associated with substantial reductions in stillbirth incidence [IRRMC-NNM = 0.94 (0.50–1.77)]. HIV status modified the effects of the IRS campaign on LBW [βIRSxHIV = 0.42 (0.05–0.78)], whereby HIV-negative women appeared to benefit from the campaign [IRR = 0.70 (0.61–0.81)], but not HIV-positive women [IRR = 1.12 (0.59–2.12)].

Conclusions

Our results support the effectiveness of the campaign in Eastern Uganda based on its benefit to LBW prevention, though HIV-positive women may require additional interventions. The IRS campaign was not associated with a substantively lower stillbirth incidence, warranting further research.