bluuebunny/crossref_metadata_2025 huggingface dataset:
Levels of Antibodies to Hepatitis B Core Antigen Are Associated With Liver Inflammation and Response to Peginterferon in Patients With Chronic Hepatitis B
Authors: Brakenhoff Sylvia M , de Knegt Robert J , Oliveira Jeffrey , van der Eijk Annemiek A , van Vuuren Anneke J , Hansen Bettina E , Janssen Harry L A , de Man Robert A , Boonstra André , Sonneveld Milan J
Published: May 2022

Background

Emerging evidence suggests a pivotal role for B-cell responses in the natural history of chronic hepatitis B. Serum levels of antibodies to hepatitis B core antigen (anti-HBc) vary across infection stages, but their role in predicting response to antiviral therapy is uncertain.

Methods

Anti-HBc levels were assessed before peginterferon (PEG-IFN) therapy in patients with chronic hepatitis B who either started de novo PEG-IFN (n = 299; 195 hepatitis B e antigen [HBeAg] positive) or started PEG-IFN as add-on to an existing nucleo(s)tide analogue backbone (n = 91; all HBeAg-positive). Associations were explored between anti-HBc and (1) serum biomarkers, (2) liver histological findings, and (3) treatment response.

Results

We studied 390 patients. The hepatitis B virus (HBV) genotype were A, B, C, and D in 24%, 9%, 16%, and 49%, respectively; 72% of patients were Caucasian. Among currently untreated HBeAg-positive patients, anti-HBc was correlated with HBV DNA, hepatitis B core-related antigen (HBcrAg), hepatitis B surface antigen (HBsAg), and HBV RNA, but not with alanine aminotransferase (ALT). Higher anti-HBc was associated with more severe histological inflammatory activity (P < .001), irrespective of HBeAg status. After de novo PEG-IFN, higher anti-HBc levels were associated with HBeAg loss, sustained response, HBsAg decline, and HBsAg clearance (P < .050). Among patients treated with add-on PEG-IFN, higher anti-HBc was associated with HBeAg loss (P = .01).

Conclusions

Serum anti-HBc levels correlate with histological inflammatory activity. Higher anti-HBc levels were associated with favorable treatment outcomes. These findings suggest that anti-HBc could be used to select patients most likely to respond to immunomodulatory therapy.

Clinical Trials Registration

NCT00114361, NCT00146705, NCT00877760, and NCT01532843.
Natural variation further increases resilience of sorghum bred for chronically drought-prone environments
Authors: Dong Hongxu , Birhan Techale , Abajebel Nezif , Wakjira Misganu , Mitiku Tesfaye , Lemke Cornelia , Vadez Vincent , Paterson Andrew H , Bantte Kassahun
Published: May 2022

Drought stress is one of the major constraints for crop production in the Sahel region of Africa. Here, we explore the potential to use natural genetic variation to build on the inherent drought tolerance of an elite sorghum cultivar, Teshale, that has been bred for Ethiopian conditions including chronic drought. We evaluated a backcross nested-association mapping population using 12 diverse founder lines crossed with Teshale under three drought-prone environments in Ethiopia. All 12 populations averaged higher head exsertion and lower leaf senescence than the recurrent parent in the two most stressful environments, reflecting new drought resilience mechanisms from the donors. A total of 154 quantitative trait loci (QTLs) were detected for eight drought-responsive traits, and their validity was supported by the fact that 113 (73.4%) overlapped with QTLs previously detected for the same traits, concentrated in regions previously associated with ‘stay-green’ traits. Allele effects showed that some favourable alleles are already present in the Ethiopian cultivar; however, the exotic donors offer rich scope for increasing drought resilience. Using model-selected SNPs associated with the eight traits identified in this study and three in a companion study, phenotypic prediction accuracies for grain yield were equivalent to genome-wide SNPs and were significantly better than random SNPs, indicating that the selected traits are predictive of sorghum grain yield.
RWP-RK domain-containing transcription factors in the Viridiplantae: biology and phylogenetic relationships
Authors: Sakuraba Yasuhito , Zhuo Mengna , Yanagisawa Shuichi
Published: May 2022

The RWP-RK protein family is a group of transcription factors containing the RWP-RK DNA-binding domain. This domain is an ancient motif that emerged before the establishment of the Viridiplantae—the green plants, consisting of green algae and land plants. The domain is mostly absent in other kingdoms but widely distributed in Viridiplantae. In green algae, a liverwort, and several angiosperms, RWP-RK proteins play essential roles in nitrogen responses and sexual reproduction-associated processes, which are seemingly unrelated phenomena but possibly interdependent in autotrophs. Consistent with related but diversified roles of the RWP-RK proteins in these organisms, the RWP-RK protein family appears to have expanded intensively, but independently, in the algal and land plant lineages. Thus, bryophyte RWP-RK proteins occupy a unique position in the evolutionary process of establishing the RWP-RK protein family. In this review, we summarize current knowledge of the RWP-RK protein family in the Viridiplantae, and discuss the significance of bryophyte RWP-RK proteins in clarifying the relationship between diversification in the RWP-RK protein family and procurement of sophisticated mechanisms for adaptation to the terrestrial environment.
The membrane associated NAC transcription factors ANAC060 and ANAC040 are functionally redundant in the inhibition of seed dormancy inArabidopsis thaliana
Authors: Song Shuang , Willems Leo A J , Jiao Ao , Zhao Tao , Eric Schranz M , Bentsink Leónie
Published: May 2022

The NAC family of transcription factors is involved in plant development and various biotic and abiotic stresses. The Arabidopsis thaliana ANAC genes ANAC060, ANAC040, and ANAC089 are highly homologous based on protein and nucleotide sequence similarity. These three genes are predicted to be membrane bound transcription factors (MTFs) containing a conserved NAC domain, but divergent C-terminal regions. The anac060 mutant shows increased dormancy when compared with the wild type. Mutations in ANAC040 lead to higher seed germination under salt stress, and a premature stop codon in ANAC089 Cvi allele results in seeds exhibiting insensitivity to high concentrations of fructose. Thus, these three homologous MTFs confer distinct functions, although all related to germination. To investigate whether the differences in function are caused by a differential spatial or temporal regulation, or by differences in the coding sequence (CDS), we performed swapping experiments in which the promoter and CDS of the three MTFs were exchanged. Seed dormancy and salt and fructose sensitivity analyses of transgenic swapping lines in mutant backgrounds showed that there is functional redundancy between ANAC060 and ANAC040, but not between ANAC060 and ANAC089.
Dynamical tides in superfluid neutron stars
Authors: Passamonti A , Andersson N , Pnigouras P
Published: May 2022

We study the tidal response of a superfluid neutron star in a binary system, focussing on Newtonian models with superfluid neutrons present throughout the star’s core and the inner crust. Within the two-fluid formalism, we consider the main aspects that arise from the presence of different regions inside the star, with particular focus on the various interfaces. Having established the relevant theory, we determine the tidal excitation of the most relevant oscillation modes during binary inspiral. Our results suggest that superfluid physics has a negligible impact on the static tidal deformation. The overwhelming contribution to the Love number is given by, as for normal matter stars, the ordinary fundamental mode (f mode). Strong entrainment, here described by a phenomenological expression, which mimics the large effective neutron mass expected at the bottom of the crust, is shown to have a significant impact on the superfluid modes, but our results for the dynamical tide are nevertheless similar to the static limit: the fundamental modes are the ones most significantly excited by the tidal interaction, with the ordinary f mode dominating the superfluid one. We also discuss the strain built up in the star’s crust during binary inspiral, showing that the superfluid f mode may (depending on entrainment) reach the limit where the crust breaks, although it does so after the ordinary f mode. Overall, our results suggest that the presence of superfluidity may be difficult to establish from binary neutron star gravitational-wave signals.
The Impact of the Covid-19 Pandemic on Smoking Among Vulnerable Populations
Authors: Wiley Rhiannon C , Oliver Anthony C , Snow Miranda B , Bunn Janice Y , Barrows Anthony J , Tidey Jennifer W , Lee Dustin C , Sigmon Stacey C , Gaalema Diann E , Heil Sarah H , Markesich Catherine , Villanti Andrea C , Higgins Stephen T
Published: May 2022

Aim

While accumulating evidence suggests that people modified their smoking during the ongoing COVID-19 pandemic, it remains unclear whether those most at risk for tobacco-related health disparities did so. The current study examined changes in smoking among several vulnerable smoker populations during the COVID-19 pandemic.

Methods

A web-based survey was distributed in 2020 to 709 adults with socioeconomic disadvantage, affective disorders, or opioid use disorder who participated in a previous study investigating the effects of very low nicotine content (VLNC) cigarettes on smoking. Current smoking status and rate, and adoption of protective health behaviors in response to the pandemic (eg social distancing, mask wearing) were examined.

Results

Among 332 survey respondents (46.8% response rate), 84.6% were current smokers. Repeated measures ANOVA showed that current cigarettes/day (CPD) was higher during COVID than pre-COVID (12.9 ± 1.0 versus 11.6 ± 1.0; p < .001). Most respondents had adopted protective health behaviors to prevent infection (>79% for all behaviors). More than half indicated that they were still leaving their homes specifically to buy cigarettes (64.6%) and were buying more packs per visit to the store (54.5%) than pre-COVID. Individuals unemployed at the time of the survey experienced greater increases in CPD (from 11.4 ± 1.4 to 13.3 ± 1.4, p = .024) as did those with higher levels of anxiety (from 11.5 ± 1.1 to 13.6 ± 1.1, p < .001).

Conclusions

Smoking increased during the COVID-19 pandemic in this sample of adults from vulnerable populations, even while most adopted protective health measures to prevent infection. Unemployment and anxiety might identify those at greatest risk for increases in tobacco use.

Implications

Individuals from populations especially vulnerable to smoking might be at risk for greater harm from cigarette smoking during times of pandemic-related stress. Public health interventions are warranted to ameliorate increases in smoking among these populations. Special attention should be paid to those experiencing unemployment and high anxiety.
Consecutive action of two BAHD acyltransferases promotes tetracoumaroyl spermine accumulation in chicory
Authors: Bernard Guillaume , Buges Julie , Delporte Marianne , Molinié Roland , Besseau Sébastien , Bouchereau Alain , Watrin Amandine , Fontaine Jean-Xavier , Mathiron David , Berardocco Solenne , Bassard Solène , Quéro Anthony , Hilbert Jean-Louis , Rambaud Caroline , Gagneul David
Published: May 2022

Fully substituted phenolamide accumulation in the pollen coat of Eudicotyledons is a conserved evolutionary chemical trait. Interestingly, spermidine derivatives are replaced by spermine derivatives as the main phenolamide accumulated in the Asteraceae family. Here, we show that the full substitution of spermine in chicory (Cichorium intybus) requires the successive action of two enzymes, that is spermidine hydroxycinnamoyl transferase-like proteins 1 and 2 (CiSHT1 and CiSHT2), two members of the BAHD enzyme family. Deletion of these genes in chicory using CRISPR/Cas9 gene editing technology evidenced that CiSHT2 catalyzes the first N-acylation steps, whereas CiSHT1 fulfills the substitution to give rise to tetracoumaroyl spermine. Additional experiments using Nicotiana benthamiana confirmed these findings. Expression of CiSHT2 alone promoted partially substituted spermine accumulation, and coexpression of CiSHT2 and CiSHT1 promoted synthesis and accumulation of the fully substituted spermine. Structural characterization of the main product of CiSHT2 using nuclear magnetic resonance revealed that CiSHT2 preferentially catalyzed N-acylation of secondary amines to form N5,N10-dicoumaroyl spermine, whereas CiSHT1 used this substrate to synthesize tetracoumaroyl spermine. We showed that spermine availability may be a key determinant toward preferential accumulation of spermine derivatives over spermidine derivatives in chicory. Our results reveal a subfunctionalization among the spermidine hydroxycinnamoyl transferase that was accompanied by a modification of free polyamine metabolism that has resulted in the accumulation of this new phenolamide in chicory and most probably in all Asteraceae. Finally, genetically engineered yeast (Saccharomyces cerevisiae) was shown to be a promising host platform to produce these compounds.
Using community-based participatory research to improve care for American Indians/Alaska Natives with type 2 diabetes mellitus
Authors: Carron Rebecca
Published: May 2022

American Indians/Alaska Natives are at increased risk for type 2 diabetes mellitus. NPs have the opportunity to intervene with culturally appropriate interventions grounded in community-based participatory research. This article provides an overview of such care that can help improve outcomes.
Treatment pearls
Authors: Miles Leslie W. , Thatcher Brandon , Thomas Michael C. , Winters Blaine
Published: May 2022

Clinicians caring for persons with mental illness should be aware of increased mortality, physical problems, and health disparities in this population. This article provides a brief overview of physical health problems in the context of mental illness as well as those related to psychotropic medications, and discusses strategies to manage treatment effectively.
Management of primary hypertension in rural populations
Authors: Bykowski Kathleen A.
Published: May 2022

Hypertension affects almost 20% of Canada's population and is even more prevalent in rural locations due to decreased availability of healthcare; lower income levels and levels of formal education; and higher rates of obesity, smoking, and alcohol use, among others. This article uses current evidence to describe the management of primary hypertension in rural populations.
NPs caring for people who are incarcerated and negatively impacted by social determinants of health
Authors: Zucker Donna M. , Reagan Louise , Clifton Jennifer , Abdulhamed Ahmed , Roscoe Lori E. , Wright Ranee' M. , Penix Darren , Shelton Deborah , Loeb Susan J.
Published: May 2022

This article explores roles filled and care provided by NPs in diverse carceral settings along with the impact of health disparities experienced as a result of social determinants of health on the chronic disease burden of people who are incarcerated. Opportunities abound for NPs to positively influence this patient population's health, but specialized education is needed.
Relative Sagittal Alignment of the Medial and Lateral Articular Surfaces of the Tibial Plateau Using Radiographic Parameters: A Radiographic Cadaveric Study
Authors: Bornes Troy D. , Kubik Jeremy F. , Klinger Craig E. , Altintas Burak , Dziadosz Daniel , Ricci William M.
Published: May 2022

Objectives:

To characterize anatomic slope (sagittal alignment) of medial and lateral articular surfaces of the tibial plateau using x-ray and computed tomography (CT).

Methods:

Fluoroscopy was used to acquire “perfect” anteroposterior (AP) images of 8 cadaveric knees by tilting a C-arm through a 30-degree cranial/caudal arc in 0.5-degree increments. Five surgeons independently selected perfect AP images that most accurately profiled medial and lateral articular surfaces. Corresponding angles were used to define tangent subchondral structures on sagittal CT that were considered as dominant bony landmarks in a protocol to determine tibial slope on sagittal CT in 46 additional cadaveric knees.

Results:

Mean perfect C-arm AP angles were 4.2 degrees ± 2.6 degrees posterior for the medial plateau and 5.0 degrees ± 3.8 degrees posterior for the lateral plateau. It was noted that images acquired within a range of angles (medial range, 1.8 degrees ± 0.7 degrees; lateral range, 3.9 degrees ± 3.8 degrees) rather than a single angle adequately profiled each compartment. Using the CT protocol, mean medial slope (5.2 degrees ± 2.3 degrees posterior; range, 0.9–11.5 degrees) was less than lateral slope (7.5 degrees ± 3.0 degrees posterior; range 0.6–12.5 degrees; P < 0.001) in 54 knees. The difference between medial and lateral slopes in any individual specimen ranged from 3.1 degree more medially to 6.8 degrees more laterally. No differences were noted between right and left knees in paired specimens.

Conclusions:

On average, tibial slope in the lateral plateau is slightly greater than that in the medial plateau, and variation exists between compartments across patients. Because tibial slope is similar between contralateral limbs, evaluating slope on the uninjured side can provide a template for sagittal plane reduction of tibial plateau fractures.
Prophylactic Desexualizing Mastectomy for an Intellectually Disabled Woman: Protective Measure or Disregard for Autonomy?
Authors: Allam Omar , Gudbranson Emily , Long Aaron S. , Alperovich Michael , Avraham Tomer
Published: May 2022

Historically, sterilization of the so-called feeble-minded has been advocated in the name of eugenics. Surrogate decision-making that impacts sexuality of the intellectually disabled presents significant ethical dilemmas. We describe a 19-year-old intellectually disabled woman who presented with her legal decision-maker for surgical correction of her asymmetric chest and hypoplastic breast. The decision-maker requested a mastectomy to make the patient’s breasts as inconspicuous as possible, and to reduce the risk of sexual assault and pregnancy. This case covers the ethical considerations on whether or not to prophylactically desexualize an intellectually disabled woman.
The E/e′ Ratio: As “Critical” As the Left Ventricular Ejection Fraction?
Authors: Krantz Mori J. , Rudo Todd , Horvath Blaine , Gregory Elizabeth , Farasat Morteza , Gore Odette , Mehler Philip S.
Published: May 2022

Ascertainment of the left ventricular ejection fraction is the primary reason for ordering echocardiography in the acute care setting; however, this parameter does not provide information regarding a patient’s volume status. As such, it cannot be reliably used to inform decisions regarding intravenous fluid resuscitation or diuresis, particularly in undifferentiated dyspnea and hypotension. This is relevant given a national quality improvement exhortation to provide aggressive fluid resuscitation as part of a “sepsis bundle.” This initiative must be tempered by the well-established increase in hospital mortality from providing intravenous fluid to patients with unrecognized heart failure, which may occur if sepsis is misdiagnosed. We describe herein, what is to our knowledge, the first description of a critically elevated Doppler ratio of mitral inflow peak E-wave velocity to the mean mitral annular velocity as a harbinger of sudden death from pulmonary edema in a patient treated with aggressive intravenous fluids as part of the “sepsis bundle.” This is utilized as a springboard for proposing a clinical algorithm focused on expedited echocardiography. It emphasized the potential value of advancing markedly the diastolic assessment of filling pressure (ratio of mitral inflow peak E-wave velocity to the mean mitral annular velocity) in the acute care setting to a level of import comparable to the left ventricular ejection fraction.
Comparison of the Efficacy and Safety of the FDA-approved Intragastric Balloon Systems in a Clinical Setting
Authors: Swei Eric , Almuhaidb Aymen , Sullivan Shelby , Al-Shahrani Abdullah , D’Souza Felicia R. , Altayar Osama , Bell Suzanne , Maday Rachel , Wagh Mihir S. , Mullady Dan , Bennett Michael , Early Dayna , Kushnir Vladimir
Published: May 2022

Background and Aims:

The gas-filled intragastric balloon (IGB) system (Obalon) and the fluid-filled IGB system (Orbera) are the current FDA-approved IGB systems to treat obesity; however, they have not been previously compared in clinical practice. The aims of this study were to compare their efficacy, tolerance, and safety in a clinical setting.

Materials and Methods:

This is a retrospective cohort study of consecutive patients treated with the gas-filled IGB or fluid-filled IGB between October 2015 and May 2020 at 2 academic centers. The primary endpoints included percent total body weight loss at balloon removal in patients who completed at least 20 weeks of therapy, the difference in adverse events that required urgent evaluation or hospitalization, and early removal in the 2 groups.

Results:

A total of 87 patients underwent successful IGB placement (gas-filled IGB n=57, age 48.9±8.8, body mass index 35.5±5 kg/m2; fluid-filled IGB n=30, age 49.2±14.3, body mass index 38.8±6 kg/m2). Eleven patients underwent early device removal. There were no differences in percent total body weight loss at balloon removal and 12 months between the balloon systems (P=0.39). Patients who received the fluid-filled IGB were more likely to require urgent evaluation or treatment, require hospital stay >24 hours, and need early balloon system removal compared with patients treated with the gas-filled IGB.

Conclusion:

In this 2-center cohort, both FDA-approved gastric balloon systems had the same effectiveness, but the gas-filled IGB had fewer serious adverse events and better tolerability than the fluid-filled IGB.
Hermann Rorschach’s (1884–1922) Clinical and Scientific Work as a Psychiatrist in Russia
Authors: Kosenko Oxana , Steger Florian
Published: May 2022

This year marks the 100th anniversary of the death of the Swiss psychiatrist Hermann Rorschach, the famous creator of an inkblot projective test. This article examines an insufficiently studied period of Rorschach's work in Russia in 1913–1914 and aims to reconstruct his clinical and scientific activities at that time. Rorschach worked in the psychoneurological sanatorium in Kryukovo near Moscow where he treated his patients with psychotherapy. During that period, he came in contact with leading psychiatrists and became a part of the Russian psychoanalytic community. Case histories of Rorschach's patients did not reveal any original approaches in his psychotherapeutic methods. Despite his lack of time for scientific work, he still coedited one of the leading psychiatry journals in Russia, Issues of Psychiatry and Neuropathology, where he published an article on the organization of services for mental health in Switzerland. Moreover, he contributed to the transfer of knowledge by publishing reviews of his Russian colleagues’ works in German journals.
Solitary Splenic Metastasis From Endometrial Carcinoma Revealed on FDG PET/CT
Authors: Xiao Liu , Li Yuhao , Li Lin
Published: May 2022

Solitary splenic metastasis from endometrial carcinoma is rare. We report a case of imaging findings of solitary splenic metastasis in a 53-year-old woman who underwent resection surgery of endometrial carcinoma of uterus 1 year ago. On FDG PET/CT, it presented as a solitary soft tissue mass with an SUVmax of 18.44. The postoperative pathology supported metastasis from endometrial carcinoma.
Emergence of protective behaviour under different risk perceptions to disease spreading
Authors: Khanjanianpak Mozhgan , Azimi-Tafreshi Nahid , Arenas Alex , Gómez-Gardeñes Jesús
Published: May 2022

The behaviour of individuals is a main actor in the control of the spread of a communicable disease and, in turn, the spread of an infectious disease can trigger behavioural changes in a population. Here, we study the emergence of individuals’ protective behaviours in response to the spread of a disease by considering two different social attitudes within the same population: concerned and risky. Generally speaking, concerned individuals have a larger risk aversion than risky individuals. To study the emergence of protective behaviours, we couple, to the epidemic evolution of a susceptible-infected-susceptible model, a decision game based on the perceived risk of infection. Using this framework, we find the effect of the protection strategy on the epidemic threshold for each of the two subpopulations (concerned and risky), and study under which conditions risky individuals are persuaded to protect themselves or, on the contrary, can take advantage of a herd immunity by remaining healthy without protecting themselves, thanks to the shield provided by concerned individuals.

This article is part of the theme issue ‘Emergent phenomena in complex physical and socio-technical systems: from cells to societies’.
The broad edge of synchronization: Griffiths effects and collective phenomena in brain networks
Authors: Buendía Victor , Villegas Pablo , Burioni Raffaella , Muñoz Miguel A.
Published: May 2022

Many of the amazing functional capabilities of the brain are collective properties stemming from the interactions of large sets of individual neurons. In particular, the most salient collective phenomena in brain activity are oscillations, which require the synchronous activation of many neurons. Here, we analyse parsimonious dynamical models of neural synchronization running on top of synthetic networks that capture essential aspects of the actual brain anatomical connectivity such as a hierarchical-modular and core-periphery structure. These models reveal the emergence of complex collective states with intermediate and flexible levels of synchronization, halfway in the synchronous–asynchronous spectrum. These states are best described as broad Griffiths-like phases, i.e. an extension of standard critical points that emerge in structurally heterogeneous systems. We analyse different routes (bifurcations) to synchronization and stress the relevance of ‘hybrid-type transitions’ to generate rich dynamical patterns. Overall, our results illustrate the complex interplay between structure and dynamics, underlining key aspects leading to rich collective states needed to sustain brain functionality.

This article is part of the theme issue ‘Emergent phenomena in complex physical and socio-technical systems: from cells to societies’.
Greater than the parts: a review of the information decomposition approach to causal emergence
Authors: Mediano Pedro A. M. , Rosas Fernando E. , Luppi Andrea I. , Jensen Henrik J. , Seth Anil K. , Barrett Adam B. , Carhart-Harris Robin L. , Bor Daniel
Published: May 2022

Emergence is a profound subject that straddles many scientific disciplines, including the formation of galaxies and how consciousness arises from the collective activity of neurons. Despite the broad interest that exists on this concept, the study of emergence has suffered from a lack of formalisms that could be used to guide discussions and advance theories. Here, we summarize, elaborate on, and extend a recent formal theory of causal emergence based on information decomposition, which is quantifiable and amenable to empirical testing. This theory relates emergence with information about a system’s temporal evolution that cannot be obtained from the parts of the system separately. This article provides an accessible but rigorous introduction to the framework, discussing the merits of the approach in various scenarios of interest. We also discuss several interpretation issues and potential misunderstandings, while highlighting the distinctive benefits of this formalism.

This article is part of the theme issue ‘Emergent phenomena in complex physical and socio-technical systems: from cells to societies’.
Understanding brain states across spacetime informed by whole-brain modelling
Authors: Vohryzek Jakub , Cabral Joana , Vuust Peter , Deco Gustavo , Kringelbach Morten L.
Published: May 2022

In order to survive in a complex environment, the human brain relies on the ability to flexibly adapt ongoing behaviour according to intrinsic and extrinsic signals. This capability has been linked to specific whole-brain activity patterns whose relative stability (order) allows for consistent functioning, supported by sufficient intrinsic instability needed for optimal adaptability. The emergent, spontaneous balance between order and disorder in brain activity over spacetime underpins distinct brain states. For example, depression is characterized by excessively rigid, highly ordered states, while psychedelics can bring about more disordered, sometimes overly flexible states. Recent developments in systems, computational and theoretical neuroscience have started to make inroads into the characterization of such complex dynamics over space and time. Here, we review recent insights drawn from neuroimaging and whole-brain modelling motivating using mechanistic principles from dynamical system theory to study and characterize brain states. We show how different healthy and altered brain states are associated to characteristic spacetime dynamics which in turn may offer insights that in time can inspire new treatments for rebalancing brain states in disease.

This article is part of the theme issue ‘Emergent phenomena in complex physical and socio-technical systems: from cells to societies’.
Ottowia testudinis sp. nov., isolated from the cloaca of a giant Asian pond turtle (Heosemys grandis)
Authors: Busse Hans-Jürgen , Kämpfer Peter , Szostak Michael P. , Spergser Joachim
Published: May 2022

A bacterial strain designated 27CT isolated from the cloaca of a giant Asian pond turtle was subjected to polyphasic taxonomic characterization. The strain was Gram-stain negative and oxidase- and catalase-positive. It had highest 16S rRNA gene sequence similarity to

Ottowia beijingensis

GCS-AN-3T (97.6 %) and

Ottowia flava

GY511T 96.0% and less than 96.0 % to other established species including

Ramlibacter rhizophilus

YS3.2.7T,

Ottowia konkukae

SK3863T,

Acidovorax caeni

E-24608T and

Ottowia thiooxydans

DSM 14619T. Phylogenetically, strain 27CT formed a branch with

O. beijingensis

GCS-AN-3T within the

Ottowia

clade. The genome size was 4.32 Mbp and the G+C content was 65.7 mol%. Strain 27CT shared highest ANIb values with

O. beijingensis

GCS-AN-3T (82.71/82.73 %) followed by

O. oryzae

KADR8-3T (78.9/79.0 %) and

O. caeni

BD-1T (73.3/75.2 %). The diagnostic diamino acid of the peptidoglycan was meso-diaminopimelic acid and the quinone system was ubiquinone Q-8. Predominant compounds in the polar lipid profile were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and phosphatidylmonomethylethanolamine. Major polyamines were 2-hydroxyputrescine and putrescine. In the fatty acid profile, summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c), C16 : 0, summed feature 8 (C18 : 1
 ω7c and/or C18 : 1
 ω6c), C14 : 0, C10 : 0 3-OH and C16 : 0 2-OH were detected. All these data identify strain 27CT as representing a novel species of the genus

Ottowia

and hence we propose the name Ottowia testudinis sp. nov. The type strain is 27CT (=CCM 9138T=LMG 32213T).
HBV induced the discharge of intrinsic antiviral miRNAs in HBV-replicating hepatocytes via extracellular vesicles to facilitate its replication
Authors: Chu Qiaofang , Li Jianhua , Chen Jieliang , Yuan Zhenghong
Published: May 2022

Hepatitis B virus (HBV), which can cause chronic hepatitis B, has sophisticated machinery to establish persistent infection. Here, we report a novel mechanism whereby HBV changed miRNA packaging into extracellular vesicles (EVs) to facilitate replication. Disruption of the miRNA machinery in hepatocytes enhanced HBV replication, indicating an intrinsic miRNA-mediated antiviral state. Interference with EV release only decreased HBV replication if there was normal miRNA biogenesis, suggesting a possible link between HBV replication and EV-associated miRNAs. Microarray and qPCR analyses revealed that HBV replication changed miRNA expression in EVs. EV incubation, transfection of miRNA mimics and inhibitors, and functional pathway and network analyses showed that EV miRNAs are associated with antiviral function, suggesting that to promote survival HBV coopts EVs to excrete anti-HBV intracellular miRNAs. These data suggest a novel mechanism by which HBV maintains its replication, which has therapeutic implications.
A systematic review of the reporting and methodological quality of studies that use Mendelian randomisation in UK Biobank
Authors: Gibson Mark J , Spiga Francesca , Campbell Amy , Khouja Jasmine N , Richmond Rebecca C , Munafò Marcus R
Published: May 2022

Background

Mendelian randomisation (MR) is a method of causal inference that uses genetic variation as an instrumental variable (IV) to account for confounding. While the number of MR articles published each year is rapidly rising (partly due to large cohort studies such as the UK Biobank making it easier to conduct MR), it is not currently known whether these studies are appropriately conducted and reported in enough detail for other researchers to accurately replicate and interpret them.

Methods

We conducted a systematic review of reporting and analysis quality of MR studies using only individual level data from the UK biobank to calculate a causal estimate. We reviewed 64 eligible articles on a 25-item checklist (based on the STROBE-MR reporting guidelines and the Guidelines for performing Mendelian Randomisation investigations). Information on article type and journal information was also extracted.

Results

Overall, the proportion of articles which reported complete information ranged from 2% to 100% across the different items. Palindromic variants, variant replication, missing data, associations between the IV and variables of exposure/outcome and bias introduced by two-sample methods used on a single sample were often not completely addressed (<11%).

There was no clear evidence that Journal Impact Factor, word limit/recommendation or year of publication predicted percentage of article completeness (for the eligible analyses) across items, but there was evidence that whether the MR analyses were primary, joint-primary or secondary analyses did predict completeness.

Conclusions

The results identify areas in which the reporting and conducting of MR studies needs to be improved and highlights that this is independent of Journal Impact Factor, year of publication or word limits/recommendations.
A New Paper Framework to Increase Reproducibility: Example Relating to Web Pharmacovigilance During COVID-19 in Italy
Authors: Rovetta Alessandro , Castaldo Lucia
Published: May 2022

Reproducibility and transparency represent some of the main problems of scientific publishing. Currently, the editorial requests of academic journals and peer reviewers can divert the authors’ attention from an accurate description of the methods adopted, thus compromising these fundamental scientific aspects. This paves the way for the voluntary falsification of data to obtain striking results. Furthermore, the excessive expansion of introduction and discussion sections increases the likelihood of introducing evaluation bias. Since peer reviewers are generally unpaid for their work, they are not required to reproduce the analysis of the studies they review but only to assess methodological accuracy, reproducibility, and plausibility. Therefore, this paper aims to emphasize that the methods and results sections are the central parts of quantitative analysis. In this regard, we firmly believe that the peer review process should, whenever possible, reproduce the analysis from scratch. Consequently, authors must be required to provide a simple and straightforward tutorial to reproduce the analysis as it was conceived both methodologically and chronologically. Ideas, insights, and discussions among the authors must also be reported. This complete description can be provided as integrative material published with the main manuscript, which is nothing more than a summary of methods and results. Such a procedure would represent the first step to improving the quality of scientific publications, waiting for unscientific concepts such as “publish or perish” to be eradicated from the academic world. In this manuscript, we provide a framework that can serve as a fully reproducible and transparent example of analysis. The aim is to investigate the Italian netizens’ web interest in paracetamol, ibuprofen, and nimesulide from 2015 to 2022, searching for causal associations with the fever symptom and COVID-19. The infodemiological tool “Google Trends” has been used to collect the data. Correlational analysis showed plausible causal associations between paracetamol, ibuprofen, and fever due to seasonal flu and COVID-19 and, although to a minor extent, COVID-19 vaccines side effects. Paracetamol was the most historically searched substance. However, the trend of ibuprofen has caught up with that of paracetamol in 2022. Interest in paracetamol, ibuprofen, and nimesulide increased substantially during the COVID-19 pandemic period. We conclude that web pharmacovigilance via Google Trends can provide relevant evidence for monitoring drug intake in relation to epidemiologically significant events such as epidemics and mass vaccination campaigns.
School immunization coverage during the COVID-19 pandemic: A retrospective cohort study
Authors: Sell Hannah , Paudel Yuba Raj , Voaklander Donald , MacDonald Shannon E.
Published: May 2022

Few studies have assessed the impact of the COVID-19 pandemic on immunization coverage for adolescents, and little is known about how coverage has changed throughout the pandemic. We aimed to: (1) assess the change in coverage for school-based vaccines in Alberta, Canada resulting from the pandemic; (2) determine whether coverage differed by geographic health zone and school type; and (3) ascertain whether coverage has returned to pre-pandemic levels. Using a retrospective cohort design, we used administrative health data to compare coverage for human papillomavirus (HPV) and meningococcal conjugate A, C, Y, W-135 (MenC-ACYW) vaccines in Alberta, Canada between pre-pandemic (2017-2018 school year) and pandemic (2019-2020 and 2020-2021 school years) cohorts (N=289,420). Coverage was also compared by health zone and authority type. The 2019-2020 cohort was followed over one year to assess catch-up. Compared to 2017-2018, immunization coverage for HPV was significantly lower in the 2019-2020 (absolute difference: 60.8%; 95% CI: 60.4-61.3%) and 2020-2021 cohorts (absolute difference: 59.9%; 95% CI: 59.4-60.3%). There was a smaller, significant decline in MenC-ACYW coverage comparing 2017-2018 to 2019-2020 (absolute difference: 6.1%; 95% CI: 5.6-6.5%) and 2020-2021 (absolute difference: 32.2%; 95% CI: 31.6-32.7%). Private schools had low coverage overall, while coverage fluctuated by zone. During follow-up of the 2019-2020 cohort, coverage for HPV and MenC-ACYW increased from 5.6% to 50.2%, and 80.7% to 83.0%, respectively. There was a substantial decrease in school-based immunization coverage during the COVID-19 pandemic, and coverage has not returned to pre-pandemic levels, suggesting further catch-up is needed.
PERFORMANCE OF αSYNUCLEIN RT-QUIC IN RELATION TO NEUROPATHOLOGICAL STAGING OF LEWY BODY DISEASE
Authors: Hall Sara , Orrù Christina , Serrano Geidy E. , Galasko Douglas , Hughson Andrew G. , Groveman Bradley R. , Adler Charles H. , Beach Thomas G. , Caughey Byron , Hansson Oskar
Published: May 2022

Currently, there is a need for diagnostic markers in Lewy body disorders (LBD). αSyn RT-QuIC has emerged as a promising assay to detect misfolded α-synuclein in clinically or neuropathologically established patients with various synucleinopathies. In this study, αSyn RT-QuIC was used to analyze lumbar CSF in a clinical cohort from the Swedish BioFINDER study and postmortem ventricular CSF in a neuropathological cohort from the Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program (AZSAND/BBDP). The BioFINDER cohort included 64 PD/PDD, 15 MSA, 15 PSP, 47 controls and two controls who later converted to PD/DLB. The neuropathological cohort included 101 cases with different brain disorders, including LBD and controls. In the BioFINDER cohort αSyn RT-QuIC identified LBD (i.e. PD, PDD and converters) vs. controls with a sensitivity of 95% and a specificity of 83%. The two controls that converted to LBD were αSyn RT-QuIC positive. Within the AZSAND/BBDP cohort, αSyn RT-QuIC identified neuropathologically verified “standard LBD” (i.e. PD, PD with AD and DLB; n=25) vs. no LB pathology (n=53) with high sensitivity (100%) and specificity (94%). Only 57% were αSyn RT-QuIC positive in the subgroup with “non-standard” LBD (i.e., AD with Lewy Bodies not meeting criteria for DLB or PD, and incidental LBD, n=23). Furthermore, αSyn RT-QuIC reliably identified cases with LB pathology in the cortex (97% sensitivity) vs. cases with no LBs or LBs present only in the olfactory bulb (93% specificity). However, the sensitivity was low, only 50%, for cases with LB pathology restricted to the brainstem or amygdala, not affecting the allocortex or neocortex. In conclusion, αSyn RT-QuIC of CSF samples is highly sensitive and specific for identifying cases with clinicopathologically-defined Lewy body disorders and shows a lower sensitivity for non-standard LBD or asymptomatic LBD or in cases with modest LB pathology not affecting the cortex.
COVID-19 Vaccine effectiveness against symptomatic infection and hospitalization in Belgium, July 2021-APRIL 2022
Authors: Braeye Toon , van Loenhout Joris , Brondeel Ruben , Stouten Veerle , Hubin Pierre , Billuart Matthieu , Chung Jenny , Vandromme Mathil , Wyndham-Thomas Chloé , Blot Koen , Catteau Lucy
Published: May 2022

1.

The COVID-19 vaccination campaign in Belgium aimed to reduce disease spread and severity. We quantified the observed vaccine effectiveness (VE) against symptomatic infection (VEi) and hospitalization (VEh).

Exhaustive data on testing and vaccination was combined with a clinical hospital survey. We estimated VEi using a test negative design and VEh using a proportional hazard analysis. We controlled for prior infection, age, sex, province of residence and calendar week of sampling. Variant of concern specific VE-estimates were obtained by time since vaccination from July 2021 to April 2022.

We included 1,433,135 persons. VEi against Delta waned from an initial estimate of 81% (95%CI 80- 82) to 56% (95%CI 56-57) 100-150 days after primary-vaccination. Booster-vaccination increased initial VEi to 84% (95%CI 83-85). Against Omicron, an initial VEi of 37% (95%CI 34-40) waned to 18% (95%CI 17-20) 100-150 days after primary-vaccination. Booster-vaccination increased VEi to 52% (95%CI 51-53) and waned to 25% (95%CI 24-27) 100-150 days after vaccination. Hybrid immunity conferred by prior infection and booster-vaccination outperformed booster-vaccination only even if the infection was over one year ago, 67% (95%CI 66-68). Initial VEh for booster-vaccination decreased from 93% (95%CI 93-94) against Delta to 87% (95%CI 85-89) against Omicron. VEh for Omicron waned to 66% (95%CI 63-70) 100-150 days after booster-vaccination.

In conclusion, we report significant immune-escape by Omicron. VEh was less affected than VEi and immune-escape was attenuated by booster-vaccination. Waning further reduced VEi- and VEh- estimates. Infection-acquired immunity offered additional protection against symptomatic infection in vaccinated persons which lasted at least one year.
Medical nurses may be effective in using silver diamine fluoride to prevent caries compared to dental hygienists in a school-based oral health program
Authors: Ruff Ryan Richard , Barry Godín Tamarinda J. , Niederman Richard
Published: May 2022

Background

The sustainability of school-based oral health programs depends on the utilization of effective, efficient treatments and the availability of a trained clinical workforce. The objective of this study was to determine whether registered nurses are comparable to dental hygienists in the application and effectiveness of silver diamine fluoride (SDF) for the prevention of dental caries.

Methods

CariedAway was a school-based study of SDF versus dental sealants and atraumatic restorations. Within the SDF arm, subjects were treated by either a licensed dental hygienist or a registered nurse, both under the supervision of a pediatric dentist. Although initial treatment assignment in CariedAway was randomized, assignment to provider was not. The proportion of children who remained caries free after two years was assessed for non-inferiority using two-group proportion tests, adjusting for the clustering effect of schools.

Results

417 children were analyzed including 298 treated by hygienists and 119 by nurses. The proportion of caries-free individuals was 0.812 and 0.798 for hygienists and nurses, respectively, for a difference of 0.014 (95% CI = -0.07, 0.098) and within the pre-determined non-inferiority margin.

Conclusions

Nurses may be effective in treating children with silver diamine fluoride in school-based oral health programs.
BA.2 omicron differs immunologically from both BA.1 omicron and pre-omicron variants
Authors: Rössler Annika , Netzl Antonia , Knabl Ludwig , Schäfer Helena , Wilks Samuel H. , Bante David , Falkensammer Barbara , Borena Wegene , von Laer Dorothee , Smith Derek , Kimpel Janine
Published: May 2022

Background

Several studies have shown that SARS-CoV-2 BA.1 omicron is an immune escape variant and current vaccines and infection with pre-omicron variants provide limited protection against BA.1. Meanwhile, however, omicron BA.2 has become the dominant variant in many countries and has replaced BA.1. As BA.2 has several mutations especially in the receptor binding and the N terminal domain compared to BA.1, we analyzed whether BA.2 shows further immune escape relative to BA.1.

Methods

We characterized neutralization profiles against the new BA.2 omicron variant in plasma samples from a variety of individuals with different numbers of exposures to infection/vaccination, including samples from previously virus-naïve, BA.2 omicron-infected individuals. To illustrate antigenic differences of the two omicron sub-variants and pre-omicron variants we performed antigenic cartography and generated antibody landscapes.

Results

Unvaccinated individuals after a single exposure to BA.2 had limited cross-neutralizing antibodies to pre-omicron variants and to BA.1. Consequently, our antigenic map, which included all Variants of Concern and both BA.1 and BA.2 omicron sub-variants, showed that both omicron sub-variants are distinct to pre-omicron variants, but that the two omicron variant are also antigenically distinct from each other. The antibody landscapes illustrate that cross-neutralizing antibodies against the whole antigenic space, as described in our maps, are generated only after three or more exposures to antigenically close variants but also after two exposures to antigenically distinct variants.

Conclusions

Here, we describe the antigenic space inhabited by the relevant SARS-CoV-2 variants, the understanding of which will have important implications for further vaccine strain adaptations.
VIGIL - Video In Geriatric Intervention Clinic: A randomised controlled feasibility trial protocol comparing face-to-face and video delivery of a specialist preoperative clinic for older people
Authors: Thorman Emma , Joughin Andrea , Carter Ben , Braude Philip
Published: May 2022

The Covid-19 pandemic resulted in significant challenges to the provision of face-to-face clinics in geriatric perioperative care (G-POC). There are no studies evaluating the use of telemedicine in this population. A pilot study at North Bristol NHS Trust demonstrated that delivery of GPOC clinics via video consultation was feasible, but did not record outcome measures to demonstrate effectiveness and was not compared to face to face clinic. This study aims to provide proof of concept examining the outcomes of virtual G-POC consultations, compared to a face-to-face clinic, using standardised perioperative outcomes. It will test the feasibility of the intervention with a view to developing a randomised controlled trial.