bluuebunny/crossref_metadata_2025 huggingface dataset:
Heavy Metal (Pb, Cd, Hg and As) Content of Some Pineapples Juice Produced in Informal Market in Abidjan, Côte d’Ivoire
Authors: Datté Yolande Amoin Aké Assi , Biégo Henri Godi , Gnigniri Lisette , KoffI Kouamé Mathias , Sanogo Siaka
Published: December 2020

Aims: The objective of this study was to determine the level of micropolluants contamination (mercury, lead, cadmium, arsenic) handcrafted pineapple juices, packaged in recovery bottles and sold on the outskirts of the city of Abidjan.

Study Design: Samples were collected from street vendors in four districts of Abidjan city (Marcory, Treichville, Cocody and Koumassi).

Place and Duration of Study: The study was conducted at the Central Food Hygiene Laboratory and Agribusiness between December 2019 and June 2020.

Methodology: 32 samples collected were analyzed by atomic absorption spectrophotometer.

Results: It appears that traces of the few metallic micropollutters were found in pineapple juices at varying rates with sometimes exceeding the maximum values recommended for lead in 75% of the pineapple juices analyzed. Considering the municipalities, 100% of the juices collected from vendors in the commune of Cocody have arsenic concentrations exceeding the maximum regulatory values. Overall, Daily Exposure Doses (DDE) (0.024 10-4 mg/kg bw of mercury, 0.345 10-4 mg/kg bw of lead, 0.001 10-3 mg/kg pc of cadmium and 0.5 10-4 mg/kg bw of arsenic) are lower than the Previsional Tolerable Dose (PTD).

Conclusion: Therefore, can the risk be eliminated for the general population? While the concentrations of metallic micropolluants found in pineapple juices remain below the thresholds for mercury and cadmium, those of lead and arsenic are high, increasing the risk of adverse effects.
Perceived Climate Resilience and Adoption of Cocoa Agroforestry in the Forest-Savannah Transition Zone of Ghana
Authors: Hashmiu Ishmael
Published: December 2020

Aims: Agroforestry is globally acknowledged as an essential component of climate-smart agriculture. Nevertheless, agroforestry adoption is low, and research is lacking on how farmers perceive the climate-related benefits of agroforestry and the implications of such perceptions on adoption. This paper assessed farmer perspectives on the effectiveness of agroforestry in enhancing the climate resilience of cocoa, and the extent to which such perceptions (in conjunction with socioeconomic factors) influence farmers’ decision to adopt cocoa agroforestry or otherwise.

Study Design: A cross-sectional survey design involving households practicing different cocoa landuse systems (agroforestry vs. full-sun monoculture) was used.

Methodology: Data were collected using structured questionnaire administered to 240 randomly selected cocoa-farming household heads.

Place and Duration of Study: The study took place in 12 rural communities in the Forest-Savannah Transition Zone of Ghana from March to September 2017.

Results: Findings indicated that while farmers unanimously acknowledged the effectiveness of cocoa agroforestry in enhancing resilience to excessive dry season temperatures, their perceptions in terms of resilience to drought differed, and were largely shaped by the kind of shade trees integrated. Overall, the majority of household heads perceived agroforestry to be the most beneficial strategy for enhancing the climate resilience of farmers. This perception significantly influenced households’ decision to adopt cocoa agroforestry, in conjunction with socioeconomic factors such as social network, sex of the household head, sex distribution of the household, and off-farm income.

Conclusion: Social network and farmers’ perception of the effectiveness of agroforestry in enhancing climate resilience are the key determinants of cocoa agroforestry adoption in the FSTZ of Ghana. Farmers who perceive agroforestry to be the most beneficial climate-resilient strategy in agriculture are more likely to adopt cocoa agroforestry. Social network can be used to enhance cocoa agroforestry adoption by serving as an effective communication channel for spreading information about the climate-related benefits of shade trees among farmers.
Starch storage capacity of sapwood is related to dehydration avoidance during drought
Authors: Pratt R. Brandon , Tobin Michael F. , Jacobsen Anna L. , Traugh Courtney A. , De Guzman Mark E. , Hayes Christine C. , Toschi Hayden S. , MacKinnon Evan D. , Percolla Marta I. , Clem Michael E. , Smith Paul T.
Published: December 2020

PREMISE

The xylem tissue of plants performs three principal functions: transport of water, support of the plant body, and nutrient storage. Tradeoffs may arise because different structural requirements are associated with different functions or because suites of traits are under selection that relate to resource acquisition, use, and turnover. The structural and functional basis of xylem storage is not well established. We hypothesized that greater starch storage would be associated with greater sapwood parenchyma and reduced fibers, which would compromise resistance to xylem tensions during dehydration.

METHODS

We measured cavitation resistance, minimum water potential, starch content, and sapwood parenchyma and fiber area in 30 species of southern California chaparral shrubs (evergreen and deciduous).

RESULTS

We found that species storing greater starch within their xylem tended to avoid dehydration and were less cavitation resistant, and this was supported by phylogenetic independent contrasts. Greater sapwood starch was associated with greater parenchyma area and reduced fiber area. For species without living fibers, the associations with parenchyma were stronger, suggesting that living fibers may expand starch storage capacity while also contributing to the support function of the vascular tissue. Drought‐deciduous species were associated with greater dehydration avoidance than evergreens.

CONCLUSIONS

Evolutionary forces have led to an association between starch storage and dehydration resistance as part of an adaptive suite of traits. We found evidence for a tradeoff between tissue mechanical traits and starch storage; moreover, the evolution of novel strategies, such as starch‐storing living fibers, may mitigate the strength of this tradeoff.
Prehospital medical equipment for care of pediatric injury patients in Japanese ambulances: a nationwide survey
Authors: Toida Chiaki , Muguruma Takashi
Published: December 2020

Aim

We evaluated the status of the allocation of medical emergency equipment suitable for pediatric patients of all ages.

Methods

In 2019, we surveyed the emergency medical officers from 728 fire defense headquarters around Japan. The questionnaire was designed to evaluate the kind and size of equipment available to ambulance crews for prehospital emergency care of injured pediatric patients. A complete pediatric equipment set was defined as a set containing equipment suitable for children aged 0–14 years.

Results

Overall, 599 (82%) fire defense headquarters responded to our survey. Of these, 596 (99.5%) declared that pediatric equipment was available to ambulance crews. The allocation rates of complete pediatric sets were considerably low: blood pressure cuff, 5%; nasopharyngeal airway, 1%; oropharyngeal airway, 7%; laryngoscope, 6%; supraglottic airway device, 13%; endotracheal tube, 0.2%; and bag‐valve‐mask, 23%. Moreover, none of these fire defense headquarters had complete pediatric equipment sets for all 14 devices assessed in this study.

Conclusions

Although most Japanese ambulances can provide prehospital emergency care to pediatric patients, this survey revealed the dispersion and deficiencies in the availability of complete pediatric equipment sets.
Paraoxonase Mimic by a Nanoreactor Aggregate Containing Benzimidazolium Calix and l‐Histidine: Demonstration of the Acetylcholine Esterase Activity
Authors: Singh Amanpreet , Saini Sanjeev , Mayank  , Kaur Navneet , Singh Ajnesh , Singh Narinder , Jang Doo Ok
Published: December 2020

An anion‐mediated preorganization approach was used to design and synthesize the benzimidazolium‐based calix compound R1⋅2 ClO4−. X‐ray crystallography analysis revealed that the hydrogen‐bonding interactions between the benzimidazolium cations and N,N‐dimethylformamide (DMF) helped R1⋅2 ClO4− encapsulate DMF molecule(s). A nanoreactor, with R1⋅2 ClO4− and l‐histidine (l‐His) as the components, was fabricated by using a neutralization method. The nanoreactor could detoxify paraoxon in 30 min. l‐His played a vital role in this process. Paraoxonase is a well‐known enzyme used for pesticide degradation. The Ellman's reagent was used to determine the percentage inhibition of the acetylcholinesterase (AChE) activity in the presence of the nanoreactor. The results indicated that the nanoreactor inhibited AChE inhibition.
Intravenous immunoglobulin therapy in adult patients with idiopathic chronic cardiomyopathy and cardiac parvovirus B19 persistence: a prospective, double‐blind, randomized, placebo‐controlled clinical trial
Authors: Hazebroek Mark R. , Henkens Michiel T.H.M. , Raafs Anne G. , Verdonschot Job A.J. , Merken Jort J. , Dennert Robert M. , Eurlings Casper , Abdul Hamid Myrurgia A. , Wolffs Petra F.G. , Winkens Bjorn , Brunner‐La Rocca Hans‐Peter , Knackstedt Christian , van Paassen Pieter , van Empel Vanessa P.M. , Heymans Stephane R.B.
Published: December 2020

Aims

Previous uncontrolled studies suggested a possible benefit of intravenous immunoglobulin (IVIg) in parvovirus B19 (B19V)‐related dilated cardiomyopathy (DCM). This randomized, double‐blind, placebo‐controlled, single‐centre trial investigated the benefits of IVIg beyond conventional therapy in idiopathic chronic DCM patients with B19V persistence.

Methods and results

Fifty patients (39 men; mean age 54 ± 11 years) with idiopathic chronic (>6 months) DCM on optimal medical therapy, left ventricular ejection fraction (LVEF) <45%, and endomyocardial biopsy (EMB) B19V load of >200 copies/µg DNA were blindly randomized to either IVIg (n = 26, 2 g/kg over 4 days) or placebo (n = 24). The primary outcome was change in LVEF at 6 months after randomization. Secondary outcomes were change in functional capacity assessed by 6‐min walk test (6MWT), quality of life [Minnesota Living with Heart Failure Questionnaire (MLHFQ)], left ventricular end‐diastolic volume (LVEDV), and EMB B19V load at 6 months after randomization. LVEF significantly improved in both IVIg and placebo groups (absolute mean increase 5 ± 9%, P = 0.011 and 6 ± 10%, P = 0.008, respectively), without a significant difference between groups (P = 0.609). Additionally, change in 6MWT [median (interquartile range) IVIg 36 (13;82) vs. placebo 32 (5;80) m; P = 0.573], MLHFQ [IVIg 0 (−7;5) vs. placebo −2 (−6;6), P = 0.904] and LVEDV (IVIg −16 ± 49 mL/m2 vs. placebo −29 ± 40 mL/m2; P = 0.334) did not significantly differ between groups. Moreover, despite increased circulating B19V antibodies upon IVIg administration, reduction in cardiac B19V did not significantly differ between groups.

Conclusion

Intravenous immunoglobulin therapy does not significantly improve cardiac systolic function or functional capacity beyond standard medical therapy in patients with idiopathic chronic DCM and cardiac B19V persistence.

Clinical Trial Registration: ClinicalTrials.gov ID NCT00892112.
Mismatch repair protein loss in cutaneous head and neck squamous cell carcinoma
Authors: Vasan Kartik , Anand Sunaina , Satgunaseelan Laveniya , Asher Rebecca , Low Hubert , Palme Carsten E. , Lee Jenny H. , Clark Jonathan R. , Gupta Ruta
Published: December 2020

Background

The treatment of advanced cutaneous head and neck cutaneous squamous cell carcinomas (HNcSCC) results in significant morbidity. Recently, immune checkpoint inhibitor treatment has been approved for DNA mismatch repair (MMR) deficient patients in a histology‐agnostic manner. This study aims to evaluate the incidence of MMR deficiency in advanced HNcSCC and its association with clinicopathologic factors.

Methods

The cohort included 176 consecutive HNcSCC cases treated with curative intent. Immunohistochemistry for MMR proteins (hMLH1, hMSH2, hMSH6, and hPMS2) was performed. Clinicopathological and survival data was collected prospectively.

Results

The incidence of MMR protein deficiency was 9.1%. There was no association between age, incidence of metachronous malignancies, clinicopathological factors, or survival outcomes.

Conclusion

A higher incidence of MMR deficiency was observed in this cohort of advanced HNcSCC. The lack of association with young age at onset or increased incidence of metachronous malignancies suggests that MMR deficiency is likely to be sporadic in HNcSCC.
Uncertainty and sensitivity of the sexual behavior changes to the current human papillomavirus vaccination campaign in Spain
Authors: Acedo Luis , Cortés Juan‐Carlos , Díez‐Domingo Javier , Sánchez‐Alonso Víctor , Tuells José , Villanueva Rafael‐Jacinto
Published: December 2020

Taking into account the public health importance of the human papillomavirus (HPV) control in the future, it is mandatory to assess the effect of the vaccination campaigns on the control of HPV spread and the associated diseases using reliable mathematical models. We propose a computational random network model with the aim of studying the transmission dynamics of HPV infections. This model reflects the herd immunity effect in the heterosexual network more accurately than the classical models. We perform a sensitivity analysis of the sexual behavior changes consisting of increasing the number of men who have sex with men (MSM), increasing the frequency of the intercourses and increasing the number of sexual partners. We find that large changes in the sexual behavior, in some extent, only have minor effects on the decline of the HPV infections in women and men in the current vaccination campaign in Spain (vaccination of young girls with a coverage of 70%). Therefore, the current vaccination program in Spain is robust for the heterosexuals. However, we cannot say the same for MSM, where they do not benefit by the herd immunity effect of the vaccination of girls, and consequently, the circulation of the virus among them remains unchanged. A consequence of the present study is that the effect of other external factors that may affect the transmission dynamics of the HPV, for instance, the tourism or the immigration, does not influence the protection provided by the current Spanish vaccination program.
Levodopa–carbidopa intrajejunal infusion in Parkinson’s disease: untangling the role of age
Authors: Morgante Francesca , Oppo Valentina , Fabbri Margherita , Olivola Enrica , Sorbera Chiara , De Micco Rosa , Ielo Giovanna Chiara , Colucci Fabiana , Bonvegna Salvatore , Novelli Alessio , Modugno Nicola , Sensi Mariachiara , Zibetti Maurizio , Lopiano Leonardo , Tessitore Alessandro , Pilleri Manuela , Cilia Roberto , Elia Antonio E. , Eleopra Roberto , Ricciardi Lucia , Cossu Giovanni
Published: December 2020

Objectives

Levodopa–Carbidopa Intrajejunal gel (LCIG) infusion is an effective intervention for people with advanced Parkinson’s disease (PD). Although age may not be a limiting factor for LCIG implant, no data are available on late elderly PD (LE-PD) subjects. In this cross-sectional, we aimed to demonstrate if older age may impact on quality of life (QoL), motor and non-motor symptoms severity, and profile of side effects in PD treated with LCIG.

Methods

Out of 512 PD subjects treated with LCIG at 9 Italian PD centers, we selected 25 LE-PD defined as age ≥ 80 years at last follow-up who were available to attend the study visit. Twenty-five PD patients (Control-PD, defined as age < 75 years at last follow-up) matched to LE-PD by disease and LCIG duration served as control group. The following motor and non-motor variables were ascertained: quality of life (PDQ-8), time spent in ON, wearing-off Questionnaire, Unified PD Rating Scale, freezing of gait questionnaire, Parkinson’s disease sleep scale-2, Non Motor Symptoms Scale (NMSS), and MOCA.

Results

No statistically significant differences were found between LE-PD and Control-PD on PDQ-8 and several motor and non-motor variables. LE-PD had less frequent and milder impulsive–compulsive behaviors and milder dyskinesia. At multivariable regression, worse quality of life was associated with UPDRS-III and NMSS scores but not to age at study visit and age at LICG implant. Rate of adverse effects was similar in both groups. Drop-out rate calculated in the whole PD cohort was comparable between the two groups.

Conclusion

Our data provide evidence that valuable LCIG infusion might be achieved in late elderly PD.
Statistics of Nascent and Mature RNA Fluctuations in a Stochastic Model of Transcriptional Initiation, Elongation, Pausing, and Termination
Authors: Filatova Tatiana , Popovic Nikola , Grima Ramon
Published: December 2020

Recent advances in fluorescence microscopy have made it possible to measure the fluctuations of nascent (actively transcribed) RNA. These closely reflect transcription kinetics, as opposed to conventional measurements of mature (cellular) RNA, whose kinetics is affected by additional processes downstream of transcription. Here, we formulate a stochastic model which describes promoter switching, initiation, elongation, premature detachment, pausing, and termination while being analytically tractable. We derive exact closed-form expressions for the mean and variance of nascent RNA fluctuations on gene segments, as well as of total nascent RNA on a gene. We also obtain exact expressions for the first two moments of mature RNA fluctuations and approximate distributions for total numbers of nascent and mature RNA. Our results, which are verified by stochastic simulation, uncover the explicit dependence of the statistics of both types of RNA on transcriptional parameters and potentially provide a means to estimate parameter values from experimental data.
Harnessing Local and Transnational Communities in the Global Protection of Underwater Cultural Heritage
Authors: Martin Josh B.
Published: December 2020

‘Communities’ – whether local, regional, or transnational – can provide an essential force in the protection of our global underwater cultural heritage (UCH). As an issue of low political concern, with its protection vulnerable to externalities and compliance weaknesses, UCH forms an ideal test case for exploring governance solutions without reliance on the state. It is also an area where communities are increasingly integrated within governance models. This article examines the theoretical justification for reducing reliance on top-down laws to protect natural and cultural heritage, exploring Ostromian arguments for greater community self- and co-regulation. Using this theoretical framework, it highlights numerous advantages of community-oriented governance in the management of a complex global concern, such as UCH protection, and underscores the role and importance of the appropriate design of meta-regulation in steering communities towards wider public objectives. The article also identifies where communities or ‘networks’ have provided important additional protection for UCH, and discusses further policy mechanisms – such as community buy-in, incentivization, and self-regulation – which could help to facilitate community-led governance in the future.
Correction: Electrochemical behaviour and analysis of Zn and Zn–Ni alloy anti-corrosive coatings deposited from citrate baths
Authors: Anwar Shams , Zhang Yahui , Khan Faisal
Published: December 2020

Correction for ‘Electrochemical behaviour and analysis of Zn and Zn–Ni alloy anti-corrosive coatings deposited from citrate baths’ by Shams Anwar et al., RSC Adv., 2018, 8, 28861–28873, DOI: 10.1039/C8RA04650F.
Social control of food supply for Russian military personnel
Authors: Bychenko Yuri , Smirnov Igor
Published: December 2020

The scientific article presents a theoretical and methodological substantiation of the problem of social control of food supply for military personnel, suggests ways to improve the interaction of military organizations with the structures of the agro-industrial complex. It has been substantiated that the most important indicators of social control are embedded in the self-assessments of servicemen in terms of the following parameters: 1) verification of compliance with the norms, rules and procedures of servicemen’s activities; 2) compliance with the norms, rules and procedures for the provision of military personnel, including food. It is proved that in modern conditions the current system of social control cannot eliminate the manifestation of negative tendencies in the system of relations of a modern military collective. The necessity is substantiated and the directions of improving the food supply system for military personnel are presented: 1) the formation of a comprehensive model of social control of food supply for military units (integration of external, internal, self-controlling substructures of control); 2) strengthening the existing model of supplying an additional component of proactive food support for military personnel, which determines the storage of food stocks and mechanisms for effective interaction with the structures of the agro-industrial complex in conditions of a destabilizing situation, local conflict, and peacekeeping operations.
Low-temperature luminescence of ScF3 single crystals under excitation by VUV synchrotron radiation
Authors: Pankratova Viktorija , Purans Juris , Pankratov Vladimir
Published: December 2020

Photoluminescence and excitation spectra of ScF3 single crystals have been measured under vacuum ultraviolet excitations utilizing undulator synchrotron radiation from 1.5 GeV storage ring of MAX IV synchrotron. The emission peak at 280 nm is explained as emission band of self-trapped excitons in ScF3. This emission is quenched at 50 K and activation energy of thermal quenching was obtained. The excitation spectrum in vacuum ultraviolet spectral range exhibits that the luminescence of self-trapped excitons effectively occurs under direct excitation in the excitonic absorption band, whereas under higher energies this excitation is strongly suppressed, however, multiplication of electronic excitation processes have been successfully identified.
Hardware and the Optical Table: Tabletop Safety Considerations
Authors: Barat Ken
Published: December 2020

For most laser users, the action takes place on the surface of the optical table, usually in the horizontal plane, maybe with an occasional periscope optic. Optical tables themselves are a wonder of technology that goes unnoticed by users, just like the air we breathe. Control measures must make the user safe but also allow work to be done in a seamless manner. One should not fight the other. In all laser safety, our motto must be “Safety through Cooperation.”
On the rise of discourse markers
Authors: Heine Bernd , Kaltenböck Gunther , Kuteva Tania , Long Haiping
Published: December 2020

Discourse markers exhibit a range of grammatical
properties that set them apart from many other lexical and
grammatical forms. A number of hypotheses have been proposed to
account for these properties. Most commonly, such accounts have
drawn on grammaticalization theory, less commonly also on the notion
of pragmaticalization. As argued in this paper, however, the rise of
discourse markers cannot be described exhaustively in terms of
parameters of grammaticalization or pragmaticalization. Looking at
the rise of two English and one French discourse marker, the paper
argues that this development is also shaped by a general strategy of
discourse processing called cooptation, which accounts for
properties of discourse markers that are beyond the scope of
grammaticalization theory. Thus, discourse markers are described
best as grammaticalized (paren)theticals.
On divergent paths and functions of ‘background’-based discourse
markers in Korean
Authors: Rhee Seongha , Koo Hyun Jung
Published: December 2020

This paper analyzes two polyfunctional discourse
markers (DMs) in Korean, kulssey and
kuntey, which share lexical and grammatical
sources, with the meaning of ‘at the time’ for
kulssey and ‘at the place’ for
kuntey. They denote the background of an
action/event (‘in such circumstances’), which is their primary
meaning when used as connective adverbs. Despite these source
commonalities, when they developed into DMs, their functional
differences are pronounced, only with a few shared functions. They
show a certain degree of positional preferences by function, but at
a more comprehensive level, left- and right-periphery do not show
rigid functional dichotomy with respect to subjectification and
intersubjectification, often hypothesized in the literature.
Instead, the role of prosody is more crucial.
On pragma-semantics of expressives
Authors: Zolyan Suren
Published: December 2020

Expressives can be understood as: (1) a
manifestation of speaker’s emotional or affective attitudes; (2) a
peculiar type of performatives; (3) a linguistic entity expressing
or displaying what is the case. The third conception is taken as the
basic one; we attempt to develop it, taking into account Bühler’s
representational theory of language and the theory of performatives
(Austin, Searle). Expressives are closely connected with behavioral
patterns, situations, and actions. An actualization of verbal
behavior (a performative component of expressives) meets its
counterpart in the verbalization of action (a descriptive
component). We suggest to describe pragma-semantics of expressives
as based on prototypical behavioural frames.
A just amazing marker in French: “Juste”
Authors: Do-Hurinville Danh-Thành
Published: December 2020

Juste belongs to those words (justement,
limite, grave, côté, question, niveau…) that today one
cannot do without, both in everyday conversation and in the media!
After pointing out that juste, from the Latin
justus, is a transcategorial unit par
excellence, as it can be an adjective, a noun, or an adverb, this
article deals with its recent adverbial use, identified orally in
the early 2000s, officially registered in Le Petit Robert de
la Langue Française in 2014. I propose that
juste is a metalinguistic marker which creates
double modalisation: it has scope both over an element X which can
be an extreme (non-gradable) adjective, a non-gradable noun phrase
(verb phrase or prepositional phrase), and over the utterance act.
This recent adverbial use of juste is analysed in
the following configurations: (1) juste and extreme
adjectives (extreme adjectives formed by the suffix
-issime, and extreme adjectives formed by the
private prefix -in); (2) juste and
non-gradable sequences [pas + gradable adjectives];
(3) juste and two non-gradable sequences
([très / trop + gradable
adjectives]; [super / hyper / ultra / supra / mega /
giga + gradable adjectives]); (4)
juste and non-gradable [noun / verb /
prepositional] phrases.
A selective transmembrane recognition mechanism by a membrane-anchored ubiquitin ligase adaptor
Authors: Arines Felichi Mae , Hamlin Aaron Jeremy , Yang Xi , Liu Yun-Yu Jennifer , Li Ming
Published: December 2020

While it is well-known that E3 ubiquitin ligases can selectively ubiquitinate membrane proteins in response to specific environmental cues, the underlying mechanisms for the selectivity are poorly understood. In particular, the role of transmembrane regions, if any, in target recognition remains an open question. Here, we describe how Ssh4, a yeast E3 ligase adaptor, recognizes the PQ-loop lysine transporter Ypq1 only after lysine starvation. We show evidence of an interaction between two transmembrane helices of Ypq1 (TM5 and TM7) and the single transmembrane helix of Ssh4. This interaction is regulated by the conserved PQ motif. Strikingly, recent structural studies of the PQ-loop family have suggested that TM5 and TM7 undergo major conformational changes during substrate transport, implying that transport-associated conformational changes may determine the selectivity. These findings thus provide critical information concerning the regulatory mechanism through which transmembrane domains can be specifically recognized in response to changing environmental conditions.
Folding Stability of Pax9 Intronic G-Quadruplex Correlates with Relative Molar Size in Eutherians
Authors: Jara-Espejo Manuel , Hawkins Melissa T R , Fogalli Giovani Bressan , Line Sergio Roberto Peres
Published: December 2020

Eutherian dentition has been the focus of a great deal of studies in the areas of evolution, development, and genomics. The development of molar teeth is regulated by an antero-to-posterior cascade mechanism of activators and inhibitors molecules, where the relative sizes of the second (M2) and third (M3) molars are dependent of the inhibitory influence of the first molar (M1). Higher activator/inhibitor ratios will result in higher M2/M1 or M3/M1. Pax9 has been shown to play a key role in tooth development. We have previously shown that a G-quadruplex in the first intron of Pax9 can modulate the splicing efficiency. Using a sliding window approach with we analyzed the association of the folding energy (Mfe) of the Pax9 first intron with the relative molar sizes in 42 mammalian species, representing 9 orders. The Mfe of two regions located in the first intron of Pax9 were shown to be significantly associated with the M2/M1 and M3/M1 areas and mesiodistal lengths. The first region is located at the intron beginning and can fold into a stable G4 structure, whereas the second is downstream the G4 and 265 bp from intron start. Across species, the first intron of Pax9 varied in G-quadruplex structural stability. The correlations were further increased when the Mfe of the two sequences were added. Our results indicate that this region has a role in the evolution of the mammalian dental pattern by influencing the relative size of the molars.
Placebo Surgery Controlled Trials
Authors: Bunzli Samantha , Choong Emma , Shadbolt Cade , Wall Laura , Nelson Elizabeth , Schilling Chris , Wilding Helen , Lohmander L. Stefan , Balogh Zsolt J. , Paolucci Francesco , Clarke Philip , Choong Peter F. M. , Dowsey Michelle M.
Published: December 2020

Objective:

To explore whether placebo surgery controlled trials achieve what they set out to do by investigating discrepancy between projected and actual design aspects of trials identified through systematic review methods.

Summary Background:

Interest in placebo surgery controlled trials is growing in response to concerns regarding unnecessary surgery and the societal cost of low-value healthcare. As questions about the justifiability of using placebo controls in surgery have been addressed, attention is now being paid to more practical concerns.

Methods:

Six databases were searched from inception - May 2020 (MEDLINE, Embase, Emcare, APA PsycInfo, CINAHL, Cochrane Library). Placebo surgery controlled trials with a published protocol were included. Three authors extracted “projected” design aspects from protocols and “actual” design aspects from main findings papers. Absolute and relative difference between projected and actual design aspects were presented for each trial. Trials were grouped according to whether they met their target sample size (“completed”) and were concluded in a timely fashion. Pairs of authors assessed risk of bias.

Results:

Of 24 trials with data available to analyse; 3 were completed and concluded within target timeframe; 10 were completed and concluded outside the target timeline; 4 were completed without clear target timeframes; 2 were incomplete and concluded within the target framework; 5 were incomplete and concluded outside the target timeline. Trials which reached the recruitment target underestimated trial duration by 88% and number of recruitment sites by 87%.

Conclusions:

Trialists need to factor additional time and sites into future placebo surgery controlled trials. A robust reporting framework of projected and actual trial design is imperative for trialists to learn from their predecessors.

Review Registration:

PROSPERO (CRD42019133296)
Influence of clinical characteristics and anti-cancer therapy on outcomes from SARS-CoV-2 infection: a systematic review and meta-analysis of 5,678 cancer patients
Authors: Chin Ik Shin , Galavotti Sara , Yip Kay Por , Curley Helen , Arnold Roland , Sharma-Oates Archana , Chegwidden Laura , Lee Siang Ing , Lee Lennard YW , Pinato David J. , Dettorre Gino M. , Palles Claire
Published: December 2020

Background

The COVID-19 pandemic started a healthcare crisis and heavily impacted cancer services.

Methods

Data from cohort studies of COVID-19 cancer patients published up until October 23rd 2020 from PubMed, PubMed Central, medRxiv and Google Scholar were reviewed. Meta-analyses using the random effects model was performed to assess the risk of death in cancer patients with COVID-19.

Results

Our meta-analyses including up to 5,678 patients from 13 studies showed that the following were all statistically significant risk factors for death following SARS-CoV-2 infection in cancer patients: age of 65 and above, presence of co-morbidities, cardiovascular disease, chronic lung disease, diabetes and hypertension. There was no evidence that patients who had received cancer treatment within 60 days of their COVID-19 diagnosis were at a higher risk of death, including patients who had recent chemotherapy.

Conclusions

Cancer patients are susceptible to severe COVID-19, especially older patients and patients with co-morbidities who will require close monitoring. Our findings support the continued administration of anti-cancer therapy during the pandemic. The analysis of chemotherapy was powered at 70% to detect an effect size of 1.2 but all other anti-cancer treatments had lower power. Further studies are required to better estimate their impact on the outcome of cancer patients.
Exploring test retest reliability and longitudinal stability of digital biomarkers for Parkinson’s disease in the m-Power dataset
Authors: Far Mehran Sahandi , Eickhoff Simon B. , Goñi María , Dukart Juergen
Published: December 2020

Background

Digital biomarkers (DB) as captured using sensors embedded in modern smart devices are a promising technology for home-based symptom monitoring in Parkinson’s disease (PD).

Objective

Despite extensive application in recent studies test-retest reliability and longitudinal stability of DB has not been well addressed in this context. We utilized the large-scale m-Power dataset to establish the test-retest reliability and longitudinal stability of gait, balance, voice and tapping tasks in an unsupervised and self-administered daily life setting in PD patients and healthy volunteers.

Methods

Intraclass Correlation Coefficients (ICC) were computed to estimate the test-retest reliability of features that also differentiate between PD and healthy volunteers. In addition, we tested for longitudinal stability of DB measures in PD and HC as well as for their sensitivity to PD medication effects.

Results

Among the features differing between PD and HC, only few tapping and voice features had good to excellent test-retest reliabilities and medium to large effect sizes. All other features performed poorly in this respect. Only few features were sensitive to medication effects. The longitudinal analyses revealed significant alterations over time across a variety of features and in particular for the tapping task.

Conclusions

These results indicate the need for further development of more standardized, sensitive and reliable DB for application in self-administered remote studies in PD patients. Motivational, learning and other confounds may cause a variation in performance that needs to be considered in DB longitudinal applications.
Vitamins D2and D3have overlapping but different effects on human gene expression revealed through analysis of blood transcriptomes in a randomised double-blind placebo-controlled food-fortification trial
Authors: Durrant Louise R. , Bucca Giselda , Hesketh Andrew , Möller-Levet Carla , Tripkovic Laura , Wu Huihai , Hart Kathryn H. , Mathers John C. , Elliott Ruan M. , Lanham-New Susan A. , Smith Colin P.
Published: December 2020

For the first time, we report the influence of vitamin D2and vitamin D3on genome-wide gene expression in whole blood from healthy women representing two ethnic groups, white European and South Asian. In this randomised placebo-controlled trial, participants were given daily physiological doses (15 µg) of either vitamin D2or D3for 12 weeks and changes in the transcriptome were compared relative to the transcriptome at baseline. While there was some overlap in the repertoire of differentially expressed genes after supplementation with each vitamin D source, most changes were specific to either vitamin D3or vitamin D2, suggesting that each form of the vitamin may have different effects on human physiology. Notably, following vitamin D3supplementation, the majority of changes in gene expression reflected a down-regulation in the activity of genes, many encoding components of the innate and adaptive immune systems. These are consistent with the emerging concept that vitamin D orchestrates a shift in the immune system towards a more tolerogenic status. Moreover, divergent changes were observed following supplementation with either vitamin D3or vitamin D2for gene expression associated with type 1 and type 2 interferon activity. This is particularly intriguing as interferons play a critical role in the innate response to infection and aberrant type 1 interferon signalling is implicated in severe COVID-19 disease. The observed differences in gene expression after supplementation with vitamin D2compared with vitamin D3warrant a more intensive investigation of the biological effects of the two forms of vitamin D on human physiology.

Significance statements

This study suggests that the influence of vitamins D2and D3on human physiology may not be the same, as deduced from differences in gene expression within whole blood.

South Asian participants were found to respond differently to vitamin D supplementation at the transcriptome level from white Europeans.

The differentially expressed immune pathways identified in this study are consistent with vitamin D orchestrating a more tolerogenic immune status and this could be relevant in the context of the severity of immune response to viral infections such as Covid-19.

The potential relevance of this study to severe Covid-19 disease is highlighted by our observed enhancement of type 1 interferon signalling by vitamin D3, but not vitamin D2.
Development and validation of total and regional body composition prediction equations from anthropometry and single frequency segmental bioelectrical impedance with DEXA
Authors: Powell Richard , De Lucia Rolfe Emanuella , Day Felix R. , Perry John R.B. , Griffin Simon J. , Forouhi Nita G. , Brage Soren , Wareham Nicholas J. , Langenberg Claudia , Ong Ken K.
Published: December 2020

Aims

Single-frequency segmental Bioelectrical Impedance Analysis (BIA) is commonly used to estimate body composition. To enhance the value of information derived from BIA, especially for use in large-scale epidemiological studies, we developed and validated equations to predict total and regional (arms, legs, trunk, android, gynoid, visceral) body composition parameters (lean mass and fat mass) from anthropometry and single-frequency (50 kHz) segmental BIA variables, using Dual Energy X-ray Absorptiometry (DEXA) as the criterion method.

Methods

The 11,559 adults (age 30 to 65) from the UK population-based Fenland Study with data on DEXA, BIA and anthropometry were randomly assigned to a Derivation sample (4,827 men; 5,732 women) or a Validation sample (500 men; 500 women). Prediction equations based on anthropometry and BIA variables were derived using forward stepwise multiple linear regression in the Fenland Derivation sample. These were validated in the Fenland Validation sample and also in the UK Biobank Imaging Study (2,392 men; 2,606 women) using Pearson correlations and Bland–Altman models.

Results and Conclusions

Bland Altman analyses revealed no significant mean bias for any predicted DEXA parameter (all P>0.05) for the fenland population. Bias expressed as % of the mean was between -0.6% and 0.5% for all parameters in both men and women, except for visceral FM and subcutaneous abdominal FM (range -3.6 to 1.1%). However, in UK Biobank most predicted parameters showed significant bias: % mean bias was <2% in both sexes only for total fat mass and total lean mass, and was >10% for leg and visceral fat mass in both sexes. In conclusion, new equations based on anthropometry and BIA variables predicted DEXA parameters with sufficient accuracy to assess relative differences between individuals, and were sufficiently accurate to predict absolute values for total body but not regional fat and lean mass.
Forecasting sub-national trends in COVID-19 vaccine uptake in the UK
Authors: de Figueiredo A.
Published: December 2020

The rollout of COVID-19 vaccines has begun to at-risk populations around the world. It is currently unclear whether rejection of the vaccine will pose challenges for achieving herd/community immunity either through large-scale rejection or localised pockets. Here we predict uptake of the vaccine at unprecedented spatial resolution across the UK using a large-scale survey of over 17,000 individuals. Although the majority of the UK population would likely take the vaccine, there is substantial heterogeneity in uptake intent across the UK. Large urban areas, including London and North West England, females, Black or Black British ethnicities, and Polish-speakers are among the least accepting. This study helps identify areas and socio-demographic groups where vaccination levels may not reach those levels required for herd immunity. Identifying clusters of non-vaccinators is extremely important in the context of achieving herd immunity as vaccination “cold-spots” can amplify epidemic spread and disproportionately increase vaccination levels required for herd protection.
RAD51AP1 mediates RAD51 activity through nucleosome interaction
Authors: Pires Elena , Sharma Neelam , Selemenakis Platon , Wu Bo , Huang Yuxin , Alimbetov Dauren S. , Zhao Weixing , Wiese Claudia
Published: December 2020

RAD51 Associated Protein 1 (RAD51AP1) is a key protein in the homologous recombination DNA repair pathway (HR). Loss of RAD51AP1 leads to defective HR, genome instability and telomere erosion. RAD51AP1 physically interacts with the RAD51 recombinase and promotes RAD51-mediated capture of the donor DNA, synaptic complex assembly and displacement-loop formation when tested with synthetic, nucleosome-free DNA substratesin vitro. In cells, however, DNA is packaged into chromatin, posing an additional barrier to the complexities of the HR reaction. How RAD51AP1 functions as an HR activator in the context of chromatin has remained unclear.

In this study, we show that RAD51AP1 binds to Nucleosome Core Particles (NCPs). We identified a C-terminal region in RAD51AP1 and its previously mapped DNA binding domain as critical for mediating the association between RAD51AP1 and both the NCP and the histone octamer. We show that RAD51AP1 is capable of promoting duplex DNA capture and initiating joint-molecule formation with the NCP and chromatinized template DNA, respectively. Together, our results suggest that RAD51AP1directlyassists the RAD51-mediated search of donor DNA in chromatin. We present a model, in which RAD51AP1 anchors the DNA template through affinity for its nucleosomes to the RAD51-ssDNA nucleoprotein filament.
Biotic and abiotic factors shaping the genome of cockle (Cerastoderma edule) in the Northeast Atlantic: a baseline for sustainable management of its wild resources
Authors: Vera Manuel , Maroso Francesco , Wilmes Sophie-B. , Hermida Miguel , Blanco Andrés , Fernández Carlos , Groves Emily , Malham Shelagh K , Bouza Carmen ,   The Cockle’s Consortium, Robins Peter E. , Martínez Paulino
Published: December 2020

Knowledge on how environmental factors shape the genome of marine species is crucial for sustainable management of fisheries and wild populations. The edible cockle (Cerastoderma edule) is a marine bivalve distributed along the Northeast Atlantic coast of Europe and is an important resource from both commercial and ecological perspectives. We performed a population genomics screening using 2b-RAD genotyping on 9,309 SNPs localised in the cockle’s genome on a sample of 536 specimens pertaining to 14 beds in the Northeast Atlantic to ascertain its genetic structure regarding environmental variation. Larval dispersal modelling considering species behaviour and interannual variability in ocean conditions was carried out, as an essential background to compare genetic information with. Cockle populations in the Northeast Atlantic were shown to be panmictic and displayed low but significant geographical differentiation across populations (FST= 0.0240; P < 0.001), albeit not across generations. We identified 441 outlier SNPs related to divergent selection, sea surface temperature being the main environmental driver following a latitudinal axis. Two main genetic groups were identified, northwards and southwards of French Brittany, in accordance with our modelling, which demonstrated a barrier for larval dispersal linked to the Ushant front. Further genetic subdivision was observed using outlier loci and considering larval behaviour. The northern group was divided into the Irish/Celtic Seas and the English Channel/North Sea, while the southern group was divided into three subgroups. This information represents the baseline for management of cockles, designing conservation strategies, founding broodstock for depleted beds, and producing suitable seed for aquaculture production.
A MYT1L Syndrome mouse model recapitulates patient phenotypes and reveals altered brain development due to disrupted neuronal maturation
Authors: Chen Jiayang , Lambo Mary E. , Ge Xia , Dearborn Joshua T. , Liu Yating , McCullough Katherine B. , Swift Raylynn G. , Tabachnick Dora R. , Tian Lucy , Noguchi Kevin , Garbow Joel R. , Constantino John N. , Gabel Harrison W. , Hengen Keith B. , Maloney Susan E. , Dougherty Joseph D.
Published: December 2020

Human genetics have defined a new autism-associated syndrome caused by loss-of-function mutations inMYT1L, a transcription factor known for enabling fibroblast-to-neuron conversions. However, howMYT1Lmutation causes autism, ADHD, intellectual disability, obesity, and brain anomalies is unknown. Here, we develop a mouse model of this syndrome. Physically,Myt1lhaploinsufficiency causes obesity, white-matter thinning, and microcephaly in the mice, mimicking clinical phenotypes. During brain development we discovered disrupted gene expression, mediated in part by loss ofMyt1lgene target activation, and identified precocious neuronal differentiation as the mechanism for microcephaly. In contrast, in adults we discovered that mutation results in failure of transcriptional and chromatin maturation, echoed in disruptions in baseline physiological properties of neurons. This results in behavioral anomalies including hyperactivity, muscle weakness and fatigue, and social alterations with more severe phenotypes in males. Overall, our findings provide insight into the mechanistic underpinnings of this disorder and enable future preclinical studies.