bluuebunny/crossref_metadata_2025 huggingface dataset:
The development of the NNBAR experiment
Authors: Backman F. , Barrow J. , Beßler Y. , Bianchi A. , Bohm C. , Brooijmans G. , Calen H. , Cederkäll J. , Damian J.I.M. , Dian E. , Di Julio D.D. , Dunne K. , Eklund L. , Ferreira M.J. , Fierlinger P. , Friman-Gayer U. , Happe C. , Holl M. , Johansson T. , Kamyshkov Y. , Klinkby E. , Kolevatov R. , Kupsc A. , Meirose B. , Milstead D. , Nepomuceno A. , Nilsson T. , Oskarsson A. , Perrey H. , Ramic K. , Rataj B. , Rizzi N. , Santoro V. , Silverstein S. , Snow W.M. , Takibayev A. , Wagner R. , Wolke M. , Yiu S.C. , Young A.R. , Zanini L. , Zimmer O.
Published: October 2022

The NNBAR experiment for the European Spallation Source
will search for free neutrons converting to antineutrons with a
sensitivity improvement of three orders of magnitude compared to the
last such search. This paper describes progress towards a conceptual
design report for NNBAR. The design of a moderator, neutron
reflector, beamline, shielding and annihilation detector is
reported. The simulations used form part of a model which will be
used for optimisation of the experiment design and quantification of
its sensitivity.
The Kronig–Penney model in a quadratic channel with δ interactions: II. Scattering approach
Authors: Smilansky Uzy
Published: October 2022

The main purpose of the present paper is to introduce a scattering approach to the study of the Kronig–Penney model in a quadratic channel with δ interactions, which was discussed in full generality in the first paper of the present series. In particular, a secular equation whose zeros determine the spectrum will be written in terms of the scattering matrix from a single δ. The advantages of this approach will be demonstrated in addressing the domain with total energy

E
∈

[

0
,

1

2

)

, namely, the energy interval where, for under critical interaction strength, a discrete spectrum is known to exist for the single δ case. Extending this to the study of the periodic case reveals quite surprising behavior of the Floquet spectra and the corresponding spectral bands. The computation of these bands can be carried out numerically, and the main features can be qualitatively explained in terms of a semi-classical framework which is developed for the purpose.
Factors associated with unmet need for support to maintain independence in later life: a systematic review of quantitative and qualitative evidence
Authors: Spiers Gemma Frances , Kunonga Tafadzwa Patience , Stow Daniel , Hall Alex , Kingston Andrew , Williams Oleta , Beyer Fiona , Bower Peter , Craig Dawn , Todd Chris , Hanratty Barbara
Published: October 2022

Background

populations are considered to have an ‘unmet need’ when they could benefit from, but do not get, the necessary support. Policy efforts to achieve equitable access to long-term care require an understanding of patterns of unmet need. A systematic review was conducted to identify factors associated with unmet need for support to maintain independence in later life.

Methods

seven bibliographic databases and four non-bibliographic evidence sources were searched. Quantitative observational studies and qualitative systematic reviews were included if they reported factors associated with unmet need for support to maintain independence in populations aged 50+, in high-income countries. No limits to publication date were imposed. Studies were quality assessed and a narrative synthesis used, supported by forest plots to visualise data.

Findings

forty-three quantitative studies and 10 qualitative systematic reviews were included. Evidence across multiple studies suggests that being male, younger age, living alone, having lower levels of income, poor self-rated health, more functional limitations and greater severity of depression were linked to unmet need. Other factors that were reported in single studies were also identified. In the qualitative reviews, care eligibility criteria, the quality, adequacy and absence of care, and cultural and language barriers were implicated in unmet need.

Conclusions

this review identifies which groups of older people may be most at risk of not accessing the support they need to maintain independence. Ongoing monitoring of unmet need is critical to support policy efforts to achieve equal ageing and equitable access to care.
Zooming in on common immune evasion mechanisms of pathogens in phagolysosomes: potential broad-spectrum therapeutic targets against infectious diseases
Authors: Selvapandiyan Angamuthu , Puri Niti , Kumar Pankaj , Alam Anwar , Ehtesham Nasreen Zafar , Griffin George , Hasnain Seyed Ehtesham
Published: October 2022

The intracellular viral, bacterial, or parasitic pathogens evade the host immune challenges to propagate and cause fatal diseases. The microbes overpower host immunity at various levels including during entry into host cells, phagosome formation, phagosome maturation, phagosome–lysosome fusion forming phagolysosomes, acidification of phagolysosomes, and at times after escape into the cytosol. Phagolysosome is the final organelle in the phagocyte with sophisticated mechanisms to degrade the pathogens. The immune evasion strategies by the pathogens include the arrest of host cell apoptosis, decrease in reactive oxygen species, the elevation of Th2 anti-inflammatory response, avoidance of autophagy and antigen cross-presentation pathways, and escape from phagolysosomal killing. Since the phagolysosome organelle in relation to infection/cure is seldom discussed in the literature, we summarize here the common host as well as pathogen targets manipulated or utilized by the pathogens established in phagosomes and phagolysosomes, to hijack the host immune system for their benefit. These common molecules or pathways can be broad-spectrum therapeutic targets for drug development for intervention against infectious diseases caused by different intracellular pathogens.
An oral gavage of lysine elicited early satiation while gavages of lysine, leucine, or isoleucine prolonged satiety in pigs
Authors: Müller Maximiliano , Xu Chenjing , Navarro Marta , Elias-Masiques Nuria , Tilbrook Alan , van Barneveld Robert , Roura Eugeni
Published: October 2022

Excess dietary amino acids (AA) may negatively affect feed intake in pigs. Previous results showed that Lys, Leu, Ile, Phe, and Glu significantly increased gut peptide secretion (i.e., cholecystokinin, glucagon-like peptide 1). However, the link between dietary AA and gut peptide secretion with changes in feeding behavior patterns has not been demonstrated to date in pigs. The aim of the present study was to determine the effect of Lys, Leu, Ile, Phe, and Glu, on feed intake and meal patterns in young pigs. Twelve male pigs (Landrace × Large White, body weight = 16.10 ± 2.69 kg) were administered an oral gavage of water (control) or Lys, Leu, Ile, Phe, Glu, or glucose (positive control) at 3 mmol.kg−1 following an overnight fasting. The experiment consisted in measuring individual feed disappearance and changes in meal pattern (including latency to first meal, first meal duration, intermeal interval, second meal duration, and number of meals) based on video footage. Compared to the control group Lys significantly (P ≤ 0.01) reduced feed intake during the first 30 min and up to 2.5 h post-gavage, including a reduction (P ≤ 0.05) in the first meal duration. Similarly, Leu and Ile also significantly decreased feed intake up to 3 h post-gavage on a cumulative count. However, the strongest (P ≤ 0.01) impacts on feed intake by the two branched chained AA were observed after the first- or second-hour post-gavage for Leu or Ile, respectively. In addition, Leu or Ile did not affect the first meal duration (P ≥ 0.05). Leu significantly increased (P ≤ 0.01) the intermeal interval while decreasing (P ≤ 0.05) the number of meals during the initial 2 h following the gavage when compared with the control group. In contrast, the oral gavages of Phe or Glu had no significant impact (P > 0.05) on the feeding behavior parameters measured relative to the control pigs. In turn, glucose had a short-lived effect on appetite by reducing (P < 0.05) feed intake for 30 min after the first-hour post-gavage. In conclusion, the impact of an oral gavage of Lys on feeding behavior is compatible with a stimulation of early satiation and an increased duration of satiety. The main impact of the oral gavages of Leu and Ile was an increase in the duration of satiety. The gastrointestinal mechanisms associated with non-bound dietary AA sensing and the impact on voluntary feed intake warrant further investigations.
Importance of Housekeeping Gene Optimization for the Analysis of mRNA Expression During Wound Healing in a Third-Degree Burn Injury Model
Authors: Arai Kenichi , Okabe Motonori , Kobashi Daisuke , Ichimura Kenji , Fathy Moustafa , Oba Jiro , Furuichi Etsuko , Yoshida Satoshi , Yoshida Toshiko
Published: October 2022

Wound healing evaluation methods in a third-degree burn injury model are categorized as histological (re-epithelialization and granulation tissue formation) and molecular (quantitative polymerase chain reaction). In general, mRNA expression is normalized to those of the housekeeping gene. Although the housekeeping gene expression is generally stable, it has been reported that the stability of these genes depends on the wound healing process and treatment method. In this study, we identified the most stable housekeeping gene (TATA-binding protein) for studying gene expression in a third-degree burn injury model, in which wound healing was promoted by grafting human amnion-derived mesenchymal cells. We investigated the wound healing effect of human amnion-derived mesenchymal cells in the injury model. The formation of granulation tissue, the differentiation from fibroblasts to myofibroblasts, and functional vascular structure were promoted in the full-thickness skin excision site by treatment with these cells. The expression of angiogenic, pro-inflammatory and anti-inflammatory related mRNA was measured and normalized to that of the housekeeping gene, showing that treatment with the cells promoted the infiltration of endothelial cells and differentiation of M1 and M2 macrophages. In conclusion, wound healing in a third-degree burn injury model can be accurately analyzed using the optimized housekeeping gene.
Asteroseismology of PG 1541 + 651 and BPM 31594 with TESS
Authors: Romero Alejandra D , da Rosa Gabriela Oliveira , Kepler S O , Bradley Paul A , Uzundag Murat , Bell Keaton J , Hermes J J , Lauffer G R
Published: October 2022

We present the photometric data from TESS for two known ZZ Ceti stars, PG 1541 + 651 and BPM 31594. Before TESS, both objects only had observations from short runs from ground-based facilities, with three and one period detected, respectively. The TESS data allowed the detection of multiple periodicities, 12 for PG 1541 + 651, and six for BPM 31594, which enables us to perform a detailed asteroseismological study. For both objects, we found a representative asteroseismic model with canonical stellar mass ∼0.61M⊙ and thick hydrogen envelopes, thicker than 10−5.3M*. The detection of triplets in the Fourier transform also allowed us to estimate mean rotation periods, being ∼22 h for PG 1541 + 651 and 11.6 h for BPM 31594, which is consistent with a range of values reported for other ZZ Ceti stars.
Constrained future brightening of solar radiation and its implication for China's solar power
Authors: He Yanyi , Yang Kun , Wild Martin , Wang Kaicun , Tong Dan , Shao Changkun , Zhou Tianjun
Published: October 2022

As Earth's primary energy source, surface downward solar radiation (Rs) determines the solar power potential and usage for climate change mitigation. Future projections of Rs based on climate models have large uncertainties that interfere with the efficient deployment of solar energy to achieve China's carbon-neutrality goal. Here we assess 24 models in the latest Coupled Model Intercomparison Project Phase 6 with historical observations in China and find systematic biases in simulating historical Rs values likely due to model biases in cloud cover and clear-sky radiation, resulting in largely uncertain projections for future changes in Rs. Based on emergent constraints, we obtain credible Rs with narrowed uncertainties by ∼56% in the mid-twenty-first century and show that the mean Rs change during 2050–2069 relative to 1995–2014 is 30% more brightening than the raw projections. Particularly in North China and Southeast China with higher power demand, the constrained projections present more significant brightening, highlighting the importance of considering the spatial changes in future Rs when locating new solar energy infrastructures.
Light-induced alteration in pigment signature and growth in a tropical surf-zone phytoplankton assemblage (southwestern Bay of Bengal, India)
Authors: Bandyopadhyay Debasmita , Biswas Haimanti
Published: October 2022

We present here the first study documenting the variability in growth and pigment signature with fluctuating light in a tropical surf-zone (coastal Bay of Bengal) phytoplankton assemblage. In response to an 8.5 times light cut-off for 3 days, 50% of the particulate organic matter (POC)-based growth rate (μPOC d−1) was maintained. Chlorophyll a (Chla) and light-harvesting pigment (LHP) contents exhibited a reverse trend without increasing POC contents, suggesting that the Chla-based growth rate can be biased under fluctuating light. Certain commonly occurring diatoms like Skeletonema, Leptocylindrus and Chaetoceros exhibited high light preference, whereas another diatom Thalassiosira proliferated at low light. Phytoplankton pigment signature was also monitored on an hourly basis over a day and the lowest LHP contents were associated with the highest photon flux densities, whereas the highest values were noticed during morning and evening hours. The ratio between photo-protective to LHP remained < 0.5, indicating that LHP contents were always greater than photo-protective pigment values and the cells were not severely light stressed. Iron (Fe) supplementation did not alter POC accumulation; photo-protective to LHP ratios also indicated Fe adequacy in this coastal water and the observed variability in the pigment signature was entirely attributed to variable light.
Analysis of the UK Government’s 10-Year Drugs Strategy—a resource for practitioners and policymakers
Authors: Holland Adam , Stevens Alex , Harris Magdalena , Lewer Dan , Sumnall Harry , Stewart Daniel , Gilvarry Eilish , Wiseman Alice , Howkins Joshua , McManus Jim , Shorter Gillian W , Nicholls James , Scott Jenny , Thomas Kyla , Reid Leila , Day Edward , Horsley Jason , Measham Fiona , Rae Maggie , Fenton Kevin , Hickman Matthew
Published: October 2022

In 2021, during a drug-related death crisis in the UK, the Government published its ten-year drugs strategy. This article, written in collaboration with the Faculty of Public Health and the Association of Directors of Public Health, assesses whether this Strategy is evidence-based and consistent with international calls to promote public health approaches to drugs, which put ‘people, health and human rights at the centre’. Elements of the Strategy are welcome, including the promise of significant funding for drug treatment services, the effects of which will depend on how it is utilized by services and local commissioners and whether it is sustained. However, unevidenced and harmful measures to deter drug use by means of punishment continue to be promoted, which will have deleterious impacts on people who use drugs. An effective public health approach to drugs should tackle population-level risk factors, which may predispose to harmful patterns of drug use, including adverse childhood experiences and socioeconomic deprivation, and institute evidence-based measures to mitigate drug-related harm. This would likely be more effective, and just, than the continuation of policies rooted in enforcement. A more dramatic re-orientation of UK drug policy than that offered by the Strategy is overdue.
Man versus Machine Learning: The Term Structure of Earnings Expectations and Conditional Biases
Authors: van Binsbergen Jules H , Han Xiao , Lopez-Lira Alejandro
Published: October 2022

We introduce a real-time measure of conditional biases to firms’ earnings forecasts. The measure is defined as the difference between analysts’ expectations and a statistically optimal unbiased machine-learning benchmark. Analysts’ conditional expectations are, on average, biased upward, a bias that increases in the forecast horizon. These biases are associated with negative cross-sectional return predictability, and the short legs of many anomalies contain firms with excessively optimistic earnings forecasts. Further, managers of companies with the greatest upward-biased earnings forecasts are more likely to issue stocks. Commonly used linear earnings models do not work out-of-sample and are inferior to those analysts provide.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
SYNTHESIS OF LIF:MG,TI NANOPARTICLES BY CO-PRECIPITATION METHOD AND EVALUATION OF INCREASING THE 5A/5 RATIO IN ALPHA AND GAMMA RADIATION
Authors: Heydari Mahmoud , Mohammadi Kheirollah , Sardari Dariush
Published: October 2022

The peak 5 in LiF: Mg, Ti includes sub-peaks 5a and 5b, which occur at the temperatures lower and higher than that of peak 5, respectively. Peak 5a in LiF:Mg,Ti occurs due to the localized recombination of trapping/luminescence center (TC/LC), in which the electron is released from the electron trap by obtaining energy from heat and recombines through the tunneling phenomenon with a hole located in the adjacent luminescence center at a distance of 3 nm. Concerning the standard TLD tablets, which are composed of micron-sized particles, the peak 5a either does not occur or appears with very low intensity, which is insignificant in terms of dosimetry. Thus, the present study focuses on synthesizing thermoluminescent nanoparticles by co-precipitation method in several stages by citing models based on the maintenance of linear behavior of thermoluminescence nanopowders up to high doses and its relationship with localized electron–hole recombination. In addition, by changing the concentration of ingredients, altering the temperature of the reaction medium and presence or absence of surfactant, nanoparticles with suitable geometric shapes were achieved. The synthesized nanopowders were irradiated with different doses of alpha and gamma, and after analyzing the glow curves, the increase in peak 5a/5 was reported as the main factor in nanodosimetry. Based on the results, the LiF: Mg, Ti thermoluminescence nanopowders can increase the 5a/5 ratio and can be used as a convenient, inexpensive and practical tool to estimate the amount of energy deposited by the beams in nanoscale.
Mental and physical health pathways linking insomnia symptoms to cognitive performance 14 years later
Authors: Zaheed Afsara B , Chervin Ronald D , Spira Adam P , Zahodne Laura B
Published: October 2022

Study Objectives

Insomnia may be a modifiable risk factor for later-life cognitive impairment. We investigated: (1) which insomnia symptoms are associated with subsequent cognitive functioning across domains; (2) whether insomnia–cognition associations are mediated by mental and physical health; and (3) whether these associations are modified by gender.

Methods

Participants included 2595 adults ages 51–88 at baseline (Mage=64.00 ± 6.66, 64.5% women) in the Health and Retirement Study. The frequency of insomnia symptoms (difficulty initiating sleep, night time awakenings, early awakenings, and feeling unrested upon awakening) at baseline (2002) were quantified using a modified Jenkins Sleep Questionnaire. Cognition was assessed in 2016 via the Harmonized Cognitive Assessment Protocol and operationalized with factor scores corresponding to five domains. Depressive symptoms and vascular conditions in 2014 were assessed via self-report. Structural equation models estimated total, indirect, and direct effects of insomnia symptoms on subsequent cognition through depressive symptoms and vascular diseases, controlling for baseline sociodemographic and global cognition.

Results

Frequent difficulty initiating sleep was associated with poorer episodic memory, executive function, language, visuoconstruction, and processing speed 14 years later (−0.06 ≤ β ≤ −0.04; equivalent to 2.2–3.4 years of aging). Depressive symptoms explained 12.3%–19.5% of these associations and vascular disease explained 6.3%–14.6% of non-memory associations. No other insomnia symptoms were associated with cognition, and no associations were modified by gender.

Conclusions

Difficulty initiating sleep in later life may predict future cognitive impairment through multiple pathways. Future research with longitudinal assessments of insomnia, insomnia treatments, and cognition is needed to evaluate insomnia as a potential intervention target to optimize cognitive aging.
Risk Factors for Cardiometabolic Disease in Professional Firefighters
Authors: McAllister Matthew J. , Gonzalez Drew E. , Leonard Megan , Martaindale M. Hunter , Bloomer Richard J. , Pence Jacquelyn , Martin Steven E.
Published: October 2022

Objective

Firefighters are plagued with cardiometabolic disease (CMD). Obesity, poor cardiorespiratory and muscular fitness, and blood lipids (low-density lipoprotein cholesterol, triglycerides, low high-density lipoprotein cholesterol) are risk factors for CMD. However, markers of oxidative stress, inflammation, and insulin resistance can provide further insight regarding CMD risk.

Methods

This study investigated the relationships between fitness metrics (cardiorespiratory and muscular fitness, percent body fat, waist circumference), blood lipids, blood pressure, and years of experience as a firefighter to blood markers of insulin resistance: Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), oxidative stress: advanced oxidation protein products (AOPPs), and inflammation: C-reactive protein.

Results

Waist circumference and blood concentrations of triglycerides were significantly related to AOPPs and HOMA-IR. Cardiorespiratory fitness was inversely related to AOPPs, HOMA-IR and C-reactive protein.

Conclusion

These findings demonstrate the importance of high cardiorespiratory fitness and low waist circumference to reduce markers of CMD.
Integrative analyses of genes about venous thromboembolism: An umbrella review of systematic reviews and meta-analyses
Authors: Lee Sangyeob , Lee Chang Han , Seo Min Seok , Yoo Jun-Il
Published: October 2022

Background:

In recent years, many studies have found possible links between gene polymorphisms and venous thromboembolism (VTE). By identifying genetic risk factors before facing environmental risk factors such as surgical interventions and COVID-19 vaccination, we could rapidly respond to the risk of VTE. The aim of this study was to perform an umbrella review of genetic variants related to VTE. Integrative gene analysis of VTE was performed to identify critical genetic variations.

Methods:

This study conducted an umbrella review of systematic reviews and meta-analyses. All included studies were selected from the PubMed/MEDLINE database. To select eligible studies, the following variables were extracted: first author name; effect size of each study genetic variant; year of publication; the number of studies included in each article; ethnicity, sample size, P values, and heterogeneity estimates. To assess cumulative evidence in genetic epidemiology about effects of gene polymorphisms on VTE, Human Genome Epidemiology Network’s Venice criteria were used. Methodological quality assessment was conducted with JBI Critical Appraisal Checklist for Systematic Reviews and Research Syntheses.

Results:

Genes provided in the present study with genetic variants associated with VTE were FVL (G1691A), Prothrombin (G20210A), MTHFR (C677T, A1298C), PAI-1 (4G/5G), factor VII activating protease (1601G > A), and endothelial protein C receptor (g.6936A_G, c.4600A_G). Among them, variants in FVL, Prothrombin, MTHFR, and PAI-1 showed high significance. Particularly, variants in Prothrombin (G20210A), MTHFR (C677T), and PAI-1 (4G/5G) had more than 2 types of model significance.

Conclusion:

The present study performed a systematic review of genetic variants associated with VTE. Our results could lead to a more comprehensive understanding of VTE etiology. These results could give a strategy of prediagnosis about evaluating individual risks of VTE who might be exposed to environmental risk factors.
Anti-glomerular basement membrane disease with rupture of the newly formed bilateral corpus luteum cysts: A case report
Authors: Luo Pei-Yi , Chen Xia , Cheng Lu , Ma Liang , Gou Shen-Ju
Published: October 2022

Rationale:

Anti-glomerular basement membrane (anti-GBM) disease during gestation is sparse and even rarer when combined with bilateral large corpus luteum cysts. In this case, we report a case of anti-GBM disease in the early stage of pregnancy with ruptured newly formed bilateral large corpus luteum cysts.

Patient concerns:

A 24-year-old female was initially diagnosed with anti-GBM disease. During treatment, abdominal distention and vaginal bleeding successively staged. The results of the first gynecological ultrasound and abdominal CT were negative.

Diagnosis:

Based on the dynamic imaging change of the ovaries, the elevated human chorionic gonadotropin (hCG) and sex hormones, and the pathological findings, a diagnosis of anti-GBM disease with rupture of the newly formed bilateral corpus luteum cysts during early pregnancy was considered.

Interventions:

The patient was treated with corticosteroids, plasma-exchange along with intensive hemodialysis. Then, to confirm the diagnosis, laparoscopic debulking of bilateral ovarian cysts and curettage were performed.

Outcomes:

After treatment, the anti-GBM antibody titer declined and the condition of the patient was still stable 2 months following discharge.

Lessons:

As clinicians, we should be aware that even if the first imaging tests are negative, the relevant indicators should be reviewed dynamically based on the condition of the patients. Additionally, this case raised the question of whether anti-GBM disease was associated with pregnancy and giant corpus luteum cysts, which needs further investigations.
Genomic epidemiology of SARS-CoV-2 within households in coastal Kenya: a case ascertained cohort study
Authors: Agoti Charles N. , Gallagher Katherine E. , Nyiro Joyce , Lambisia Arnold W. , Murunga Nickson , Mohammed Khadija Said , Ndwiga Leonard , Morobe John M. , Mburu Maureen W. , Ongera Edidah M. , Makori Timothy O. , Phan My V.T. , Cotten Matthew , Ochola-Oyier Lynette Isabella , Dellicour Simon , Bejon Philip , Githinji George , Nokes D. James
Published: October 2022

Analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences from household infections may provide useful epidemiological information for future control measures. Between December 2020 and July 2022, we conducted a case-ascertained household cohort study whereby households were recruited if a member was either a SARS-CoV-2 case or contact of a confirmed case. A total of 765 members of 214 households were prospectively monitored for SARS-CoV-2 infection and transmission. Follow-up visits collected a nasopharyngeal/oropharyngeal (NP/OP) swab on days 1, 4 and 7 for RT-PCR diagnosis. If any of these were positive, further swabs were collected on days 10, 14, 21 and 28. Of 2,780 NP/OP swabs collected, 540 (19.4%) tested SARS-CoV-2 positive and viral genome sequences were recovered for 288 (53.3%) positive samples. The genomes belonged to 23 different Pango lineages. Phylogenetic analysis including contemporaneous Coastal Kenya data estimated 233 putative transmission events involving 162 members of the 89 households, of which 60 (25%) were intra-household transmission events while 173 (75%) were infections that likely occurred outside the households. In 34 (38%) households, multiple virus introductions were observed (up to six) within the one-month follow-up period, in contrast to high-income settings, where a single introduction seemed to occur during epidemic waves. Our findings suggests that in this setting control of respiratory virus spread by household member isolation will be ineffective.
Increased lipid peroxidation and lowered antioxidant defenses predict methamphetamine induced psychosis
Authors: Al-Hakeim Hussein Kadhem , Altufaili Mazin Fadhil , Almulla Abbas F. , Moustafa Shatha Rouf , Maes Michael
Published: October 2022

Background

A significant percentage of methamphetamine (MA) dependent patients develop psychosis. However, the associations between oxidative pathways and MA-induced psychosis (MIP) are not well delineated.

Objective

The aim of this study is to delineate whether acute MA intoxication in MA dependent patients is accompanied by increased nitro-oxidative stress and whether the latter is associated with MIP.

Method

We recruited 30 healthy males and 60 acutely intoxicated MA males with MA dependence and assessed severity of MA use and dependence and psychotic symptoms during intoxication and measured serum oxidative toxicity (OSTOX) biomarkers including oxidized high (oxHDL) and low (oxLDL)-density lipoprotein, myeloperoxidase (MPO), malondialdehyde (MDA), and nitric oxide (NO), and antioxidant defenses (ANTIOX) including HDL-cholesterol, zinc, glutathione peroxidase (GPx), total antioxidant capacity (TAC), and catalase-1.

Results

A large part (50%, n=30) of patients with MA dependence could be allocated to a cluster characterized by high psychosis ratings including delusions, suspiciousness, conceptual disorganization and difficulties abstract thinking and an increased OSTOX/ANTIOX ratio. Partial Least Squares analysis showed that 29.9% of the variance in MIP severity (a first factor extracted from psychosis, hostility, excitation, mannerism, and formal thought disorder scores) was explained by HDL, TAC and zinc (all inversely) and oxLDL (positively). MA dependence and dosing explained together 44.7% of the variance in the OSTOX/ANTIOX ratio.

Conclusion

MA dependence and intoxication are associated with increased oxidative stress and lowered antioxidant defenses, which both increase risk of MIP during acute intoxication. MA dependence is accompanied by increased atherogenicity due to lowered HDL and increased oxLDL and oxHDL.
Activation of an injury-associated transient progenitor state in the epicardium is required for zebrafish heart regeneration
Authors: Xia Yu , Duca Sierra , Perder Björn , Dündar Friederike , Zumbo Paul , Qiu Miaoyan , Yao Jun , Cao Yingxi , Harrison Michael R. , Zangi Lior , Betel Doron , Cao Jingli
Published: October 2022

The epicardium, a mesothelial cell tissue that encompasses vertebrate hearts, supports heart regeneration after injury through paracrine effects and as a source of multipotent progenitors. However, the progenitor state in the adult epicardium has yet to be defined. Through single-cell RNA-sequencing of isolated epicardial cells from uninjured and regenerating adult zebrafish hearts, we defined the epithelial and mesenchymal subsets of the epicardium. We further identified a transiently activated epicardial progenitor cell (aEPC) subpopulation marked byptx3aandcol12a1bexpression. Upon cardiac injury, aEPCs emerge from the epithelial epicardium, migrate to enclose the wound, undergo epithelial-mesenchymal transition (EMT), and differentiate into mural cells andpdgfra+hapln1a+mesenchymal epicardial cells. These EMT and differentiation processes are regulated by the Tgfβ pathway. Conditional ablation of aEPCs blocked heart regeneration through reduced Nrg1 expression and mesenchymal cell number. Our findings identify a transient progenitor population of the adult epicardium that is indispensable for heart regeneration and highlight it as a potential target for enhancing cardiac repair.
Influenza-associated hospitalisation and mortality rates among global Indigenous populations; a systematic review and meta-analysis
Authors: Betts Juliana M. , Weinman Aaron L. , Oliver Jane , Braddick Maxwell , Huang Siyu , Nguyen Matthew , Miller Adrian , Tong Steven Y.C. , Gibney Katherine B.
Published: October 2022

Background

More than 50 million influenza infections and over 100,000 deaths from influenza occur annually. While Indigenous populations experience an inequitable influenza burden, the magnitude of this inequity has not previously been estimated on a global scale. This study compared rates of influenza-associated hospitalisation and mortality between Indigenous and non-Indigenous populations globally.

Methods

A systematic review and meta-analysis was conducted including literature published prior to 13 July 2021. Eligible articles either reported a rate ratio (RR) comparing laboratory-confirmed influenza-associated hospitalisation and/or mortality between an Indigenous population and a corresponding benchmark population, or reported sufficient information for this to be calculated using publicly available data. Findings were reported by country/region and pooled by country and period (pandemic/seasonal) when multiple studies were available using a random-effects model. The I2statistic assessed variability between studies.

Results

Thirty-six studies (moderate/high quality) were included; all from high or high-middle income countries. The pooled influenza-associated hospitalisation RR (HRR) for indigenous compared to benchmark populations was 5·7 (95% CI: 2·7–12·0) for Canada, 5·2 (2.9–9.3) for New Zealand, and 5.2 (4.2–6.4) for Australia. Of the Australian studies, the pooled HRR for seasonal influenza was 3.1 (2·7–3·5) and for pandemic influenza was 6·2 (5·1–7·5). Heterogeneity was slightly higher among studies of pandemic influenza than seasonal influenza. The pooled mortality RR was 4.1 (3·0–5.7) in Australia and 3·3 (2.7–4.1) in the United States.

Conclusions

Ethnic inequities in severe influenza persist and must be addressed by reducing disparities in the underlying determinants of health. Influenza surveillance systems worldwide should include Indigenous status to determine the extent of the disease burden among Indigenous populations. Ethnic inequities in pandemic influenza illustrate the need to prioritise Indigenous populations in pandemic response plans.
Comparison of Simulated Outcomes Between Stool- and Blood-Based Colorectal Cancer Screening Tests
Authors: Fendrick A. Mark , Vahdat Vahab , Chen Jing Voon , Lieberman David , Karlitz Jordan J. , Limburg Paul J. , Ozbay A. Burak , Kisiel John B.
Published: October 2022

Objectives

The Centers for Medicare & Medicaid Services (CMS) recommends covering blood-based tests meeting proposed minimum performance thresholds for colorectal cancer (CRC) screening. Outcomes were compared between currently available stool-based screening tests and a hypothetical blood-based test meeting CMS minimum thresholds.

Methods

Using the CRC-AIM model, outcomes were simulated for average-risk individuals screened between ages 45-75 years with triennial multi-target stool DNA (mt-sDNA), annual fecal immunochemical test (FIT), and annual fecal occult blood test (FOBT). Per CMS guidance, blood-based CRC screening was modeled triennially, with 74% CRC sensitivity and 90% specificity. Although not specified by CMS, adenoma sensitivity was set between 10-20%. Published adenoma and CRC sensitivity and specificity were used for stool-based tests. Adherence was set at (a) 100%, (b) 30-70%, in 10% increments, and (c) real-world rates for stool-based tests (mt-sDNA=65.6%; FIT=42.6%; FOBT=34.4%).

Results

Assuming perfect adherence, a blood-based test produced ≥19 lower LYG than stool-based strategies. At the best-case scenario for blood-based tests (100% adherence and 20% adenoma sensitivity), mt-sDNA at real-world adherence achieved more LYG (287.2 vs 297.1, respectively) with 14% fewer colonoscopies. At 100% blood-based test adherence and real-world mt-sDNA and FIT adherence, the blood-based test would require advanced adenoma sensitivity of 30% to reach the LYG of mt-sDNA (297.1) and approximately 15% sensitivity to reach the LYG of FIT (258.9).

Conclusions

This model suggests that blood-based tests with CMS minimally-acceptable CRC sensitivity and low advanced adenoma sensitivity will frequently yield inferior outcomes to stool-based testing across a wide range of adherence assumptions.
A cold-blooded vertebrate shows integration of antimicrobial defenses and tissue repair through fever
Authors: Haddad Farah , Soliman Amro M. , Wong Michael E. , Albers Emilie H. , Semple Shawna L. , Torrealba Débora , Heimroth Ryan D. , Nashiry Asif , Tierney Keith B. , Barreda Daniel R.
Published: October 2022

Multiple lines of evidence support the value of moderate fever to host survival, but the mechanisms involved remain unclear. This is difficult to establish in warm-blooded animal models, given the strict programs controlling core body temperature and the physiological stress that results from their disruption. Thus, we took advantage of a cold-blooded teleost fish that offered natural kinetics for the induction and regulation of fever and a broad range of tolerated temperatures. A custom swim chamber, coupled to high-fidelity quantitative positional tracking, showed remarkable consistency in fish behaviours and defined the febrile window. Animals exerting fever engaged pyrogenic cytokine gene programs in the CNS, increased efficiency of leukocyte recruitment into the immune challenge site, and markedly improved pathogen clearancein vivo, even when an infecting bacterium grew better at higher temperatures. Contrary to earlier speculations for global upregulation of immunity, we identified selectivity in the protective immune mechanisms activated through fever. Fever then inhibited inflammation and markedly improved wound repair. Artificial mechanical hyperthermia, often used as a model of fever, recapitulated some but not all benefits achieved through natural host-driven dynamic thermoregulation. Together, our results define fever as an integrative host response that regulates induction and resolution of acute inflammation, and demonstrate that this integrative strategy emerged prior to endothermy during evolution.
The nucleolar protein GNL3 prevents resection of stalled replication forks
Authors: Lebdy Rana , Canut Marine , Patouillard Julie , Cadoret Jean-Charles , Letessier Anne , Ammar Josiane , Basbous Jihane , Urbach Serge , Miotto Benoit , Constantinou Angelos , Abou Merhi Raghida , Ribeyre Cyril
Published: October 2022

DNA replication requires specific proteins that protect replication forks and so prevent the formation of DNA lesions that may damage the genome. Identification of new proteins involved in these processes is essential to understand how cancer cells tolerate DNA lesions. Here we show that human GNL3/nucleostemin, a GTP-binding protein localized mostly in the nucleolus and highly expressed in cancer cells, prevents nuclease-dependent resection of nascent DNA in response to exogenous replication stress. We demonstrate that inhibition of origin firing decreases this resection, indicating that the increased replication origin firing seen upon GNL3 depletion mainly accounts for the observed DNA resection. We show that GNL3 and DNA replication initiation factor ORC2 interact in the nucleolus and that the concentration of GNL3 in the nucleolus is required to limit DNA resection in response to replicative stress. We propose that the accurate control of origin firing by GNL3, possibly through the regulation of ORC2 sub-nuclear localization, is critical to prevent nascent DNA resection in response to replication stress.
Biogeographic Distribution of Five Antarctic Cyanobacteria Using Large-Scale k-mer Searching with sourmash branchwater
Authors: Lumian Jessica , Sumner Dawn , Grettenberger Christen , Jungblut Anne D. , Irber Luiz , Pierce-Ward N. Tessa , Brown C. Titus
Published: October 2022

Cyanobacteria form diverse communities and are important primary producers in Antarctic freshwater environments, but their geographic distribution patterns in Antarctica and globally are still unresolved. There are however few genomes of cultured cyanobacteria from Antarctica available and therefore metagenome-assembled genomes (MAGs) from Antarctic cyanobacteria microbial mats provide an opportunity to explore distribution of uncultured taxa. These MAGs also allow comparison with metagenomes of cyanobacteria enriched communities from a range of habitats, geographic locations, and climates. However, most MAGs do not contain 16S rRNA gene sequences, making a 16S rRNA gene-based biogeography comparison difficult. An alternative technique is to use large-scale k-mer searching to find genomes of interest in public metagenomes.

This paper presents the results of k-mer based searches for 5 Antarctic cyanobacteria MAGs from Lakes Fryxell and Lake Vanda, assigned the namesPhormidium pseudopriestleyi, aMicrocoleus, aLeptolyngbya, aPseudanabaena, and aNeosynechococcus(Lumian et al., 2021, Lumian et al., 2022, in prep.) in 498,942 unassembled metagenomes from the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA). TheMicrocoleusMAG was found in a wide variety of environments,P. pseudopriestleyiwas found in environments with challenging conditions, theNeosynechococcuswas only found in Antarctica, and theLeptolyngbyaandPseudanabaenaMAGs were found in Antarctic and other cold environments. The findings based on metagenome matches and global comparisons suggest that these Antarctic cyanobacteria have distinct distribution patterns ranging from locally restricted to global distribution across the cold biosphere and other climatic zones.
The E2F4/p130 repressor complex cooperates with oncogenic ΔNp73α to promote cell survival in human papillomavirus 38 E6/E7-transformed keratinocytes and in cancer cells
Authors: Taverniti Valerio , Krynska Hanna , Venuti Assunta , Straub Marie-Laure , Sirand Cécilia , Lohmann Eugenie , Romero-Medina Maria Carmen , Moro Stefano , Robitaille Alexis , Negroni Luc , Martinez-Zapien Denise , Masson Murielle , Tommasino Massimo , Zanier Katia
Published: October 2022

Tumor suppressor p53 and its related proteins, p63 and p73, can be synthesized as multiple isoforms lacking part of the N- or C-terminal regions. Specifically, high expression of the ΔNp73α isoform is notoriously associated with various human malignancies characterized by poor prognosis. This isoform is also accumulated by oncogenic viruses such as Epstein–Barr virus (EBV), as well as genus beta human papillomaviruses (HPV) that appear to be involved in carcinogenesis. To gain additional insight into ΔNp73α mechanisms, we have performed proteomics analyses using human keratinocytes transformed by the E6 and E7 proteins of the beta-HPV type 38 virus as an experimental model (38HK). We find that ΔNp73α associates with the E2F4/p130 repressor complex through a direct interaction with E2F4. This interaction is favored by the N-terminal truncation of p73 characteristic of ΔNp73 isoforms. Moreover, it is independent of the C-terminal splicing status, suggesting that it could represent a general feature of ΔNp73 isoforms (α, β, γ, δ, ε, ζ, θ, η, and η1). We also show that the ΔNp73α- E2F4/p130 complex inhibits the expression of specific genes, including genes encoding for negative regulators of proliferation, both in 38HK and in HPV-negative cancer-derived cell lines. Consistently, silencing of E2F4 in 38HK and in cancer cells results in induction of senescence. In conclusion, we have identified and characterized a novel transcriptional regulatory complex that exerts pro-survival functions in transformed cells.

IMPORTANCE

The TP53 gene is mutated in about 50% of human cancers. In contrast, the TP63 and TP73 genes are rarely mutated but rather expressed as ΔNp63 and ΔNp73 isoforms in a wide range of malignancies, where they act as p53 antagonists. Accumulation of ΔNp63 and ΔNp73, which is associated with chemoresistance, can result from infection by oncogenic viruses such as EBV or HPV. Our study focuses on the highly carcinogenic ΔNp73α isoform and uses a viral model of cellular transformation. We unveil a physical interaction between ΔNp73α and the E2F4/p130 complex involved in cell cycle control, which rewires the E2F4/p130 transcriptional program. Consistently, we find that E2F4 gains pro-survival functions in transformed cells expressing ΔNp73α. This report shows, for the first time, that ΔNp73 isoforms acquire novel protein-protein interactions with respect to the TAp73 tumor suppressor. This situation is analogous to the gain-of-function interactions of p53 mutants supporting cellular proliferation.
Topic modelling with ICD10-informed priors identifies novel genetic loci associated with multimorbidities in UK Biobank
Authors: Zhang Yidong , Jiang Xilin , Mentzer Alexander J , McVean Gil , Lunter Gerton
Published: October 2022

Studies of disease incidence have identified thousands of genetic loci associated with complex traits. However, many diseases occur in combinations that can point to systemic dysregulation of underlying processes that affect multiple traits. We have developed a data-driven method for identifying such multimorbidities from routine healthcare data that combines topic modelling through Bayesian binary non-negative matrix factorization with an informative prior derived from the hierarchical ICD10 coding system. Through simulation we show that the method, treeLFA, typically outperforms both Latent Dirichlet Allocation (LDA) and topic modelling with uninformative priors in terms of inference accuracy and generalisation to test data, and is robust to moderate deviation between the prior and reality. By applying treeLFA to data from UK Biobank we identify a range of multimorbidity clusters in the form of disease topics ranging from well-established combinations relating to metabolic syndrome, arthropathies and cancers, to other less well-known ones, and a disease-free topic. Through genetic association analysis of inferred topic weights (topic-GWAS) and single diseases we find that topic-GWAS typically finds a much smaller, but only partially-overlapping, set of variants compared to GWAS of constituent disease codes. We validate the genetic loci (only) associated with topics through a range of approaches. Particularly, with the construction of PRS for topics, we find that compared to LDA, treeLFA achieves better prediction performance on independent test data. Overall, our findings indicate that topic models are well suited to characterising multimorbidity patterns, and different topic models have their own unique strengths. Moreover, genetic analysis of multimorbidity patterns can provide insight into the aetiology of complex traits that cannot be determined from the analysis of constituent traits alone.