bluuebunny/crossref_metadata_2025 huggingface dataset:
Metagenomes of Red Sea subpopulations challenge the use of morphology and marker genes to assess Trichodesmium diversity
Authors: Koedooder Coco , Landou Etai , Zhang Futing , Wang Siyuan , Basu Subhajit , Berman-Frank Ilana , Shaked Yeala , Rubin-Blum Maxim
Published: February 2022

The bloom forming Trichodesmium are filamentous cyanobacteria of key interest due to their ability to fix carbon and nitrogen within an oligotrophic marine environment. Trichodesmium blooms typically comprise a complex assemblage of subpopulations and colony-morphologies that are predicted to exhibit distinct ecological lifestyles. Here, we assessed the poorly studied diversity of Trichodesmium in the Red Sea, based on metagenome-assembled genomes (MAGs) and hetR gene-based phylotyping.

We assembled four non-redundant MAGs from morphologically distinct Trichodesmium colonies (tufts, dense and thin puffs). T. thiebautii (puffs) and T. erythraeum (tufts) were the dominant species within these morphotypes. While subspecies diversity is present for both T. thiebautii and T. erythraeum, a single T. thiebautii genotype comprised both thin and dense puff morphotypes, and we therefore hypothesize that the phenotypic variation between these morphologies is likely attributed to gene regulation. Additionally, we found the rare non-diazotrophic clade IV and V genotypes, related to T. nobis and T. miru respectively, that likely occurred as single filaments. HetR gene phylogeny indicates that the genotype in clade IV could represent the species T. contortum.

We further show that hetR phylotyping can overestimate the taxonomic diversity of Trichodesmium, as two copies of the hetR gene were present within T. thiebautii genomes, one of which misidentified this lineage as T. aureum. Taken together, our results highlight the importance of re-assessing Trichodesmium taxonomy while showing the ability of genomics to capture the complex diversity and distribution of Trichodesmium populations.
Defective mitochondrial-lysosomal axis promotes extracellular vesicles release of mitochondrial components in Huntington’s Disease
Authors: Beatriz Margarida , Vilaça Rita , Anjo Sandra I. , Manadas Bruno , Januário Cristina , Rego A. Cristina , Lopes Carla
Published: February 2022

Mitochondrial and autophagy dysfunction are mechanisms proposed to be involved in the pathogenesis of several neurodegenerative diseases. Huntington’s disease (HD) is a progressive neurodegenerative disorder associated with mutant Huntingtin-induced abnormalities in neuronal mitochondrial dynamics and quality control. Former studies suggest that the removal of defective mitochondria may be compromised in HD. The mitochondrial quality control is a complex, well-orchestrated pathway that can be compromised through mitophagy dysregulation or impairment in the mitochondrial-lysosomal axis. Another mitochondrial stress response is the generation of mitochondrial-derived vesicles that fuse with the endolysosomal system and form multivesicular bodies that are extruded from cells as extracellular vesicles (EVs).

In this study, we comprehensively characterized the mitochondrial and autophagy alterations in premanifest and manifest HD patients and performed a proteomic and genomic EVs profile. We observed that manifest HD patients exhibit mitochondrial and autophagy impairment associated with enhanced EVs release. Further, we detected mitochondrial components in EVs released by HD cells and in neuron-derived EVs. The EV-associated mtDNA copies were elevated in manifest HD patients suggesting to be an alternative pathway for secretion of reactive mitochondrial components. This study provides a novel framework connecting EVs enhanced release of mitochondrial components to mitochondrial and lysosomal dysfunction in HD.
RNA triplex structures revealed by WAXS-driven MD simulations
Authors: Chen Yen-Lin , He Weiwei , Kirmizialtin Serdal , Pollack Lois
Published: February 2022

RNA triple helices are commonly observed tertiary motifs that are increasingly associated with critical biological functions, including signal transduction. Because the recognition of their biological importance is relatively recent, their full range of structures and function has not yet been elucidated. The integration of solution wide-angle X-ray scattering (WAXS) with data-driven molecular dynamics (MD) simulations, described here, provides a new way to capture the structures of major-groove RNA triplexes that evade crystallographic characterization. This method yields excellent agreement between measured and computed WAXS profiles, and allows for an atomically detailed visualization of these motifs. Using correlation maps, the relationship between well-defined features in the scattering profiles and real space characteristics of RNA molecules is easily defined, including the subtle conformational variations in the double-stranded RNA upon the incorporation of a third strand by base-triples. This readily applicable approach provides unique insight into some of the interactions that stabilize RNA tertiary structure and enable function.
A novel Bayesian factor analysis method improves detection of genes and biological processes affected by perturbations in single-cell CRISPR screening
Authors: Zhou Yifan , Luo Kaixuan , Chen Mengjie , He Xin
Published: February 2022

CRISPR screening coupled with single-cell RNA-sequencing has emerged as a powerful tool to characterize the effects of genetic perturbations on the whole transcriptome at a single-cell level. However, due to the sparsity and complex structure of data, analysis of single-cell CRISPR screening data remains challenging. In particular, standard differential expression analysis methods are often under-powered to detect genes affected by CRISPR perturbations. We developed a novel method for such data, called Guided Sparse Factor Analysis (GSFA). GSFA infers latent factors that represent co-regulated genes or gene modules, and by borrowing information from these factors, infers the effects of genetic perturbations on individual genes. We demonstrated through extensive simulation studies that GSFA detects perturbation effects with much higher power than state-of-the-art methods. Using single-cell CRISPR data from human CD8+ T cells and neural progenitor cells, we showed that GSFA identified biologically relevant gene modules and specific genes affected by CRISPR perturbations, many of which were missed by existing methods, providing new insights into the functions of genes involved in T cell activation and neurodevelopment.
Solution structure of the phosphatidylinositol 3-phosphate binding domain from theLegionellaeffector SetA
Authors: Beck Wendy H.J. , Enoki Thais A. , Wu Xiaochun , Zhang Qing , Nicholson Linda K. , Oswald Robert E. , Mao Yuxin
Published: February 2022

Legionella pneumophilais a facultative intracellular pathogen that causes Legionnaires’ disease or Pontiac fever in humans upon accidental inhalation ofLegionella-contaminated aerosols. During infection,L. pneumophilasecretes more than 300 effectors into the host for the biogenesis of a replication-permissive niche, known as theLegionella containingvacuole (LCV). Among these, a large number of effectors harbor protein domains that recognize specific phosphoinositide (PI) lipids and mediate the anchoring of these effectors to the surface of LCV or other host membrane-bound organelles. TheLegionellaeffector SetA contains a unique C-terminal domain (SetA-CTD) that has been shown to specifically bind with phosphatidylinositol-3-phosphate (PI(3)P) and target SetA to endosomes and LCVs. Here, we report the NMR solution structure of SetA-CTD, which mainly comprises a four α-helix bundle. The structure reveals a basic pocket at one end of the α-helix bundle for PI(3)P binding and two hydrophobic loops for membrane insertion. Mutations of key residues involved in lipid binding result in the loss of SetA in membrane association and endosomal localization. Structural comparison with other PI(3)P-binding domains highlights a general theme applied by multiple families of phosphoinositide-binding domains across species.
Ultrahigh-throughput directed evolution of a metal-free α/β-hydrolase with a Cys-His-Asp triad into an efficient phosphotriesterase
Authors: Schnettler Fernández David , Klein Oskar James , Kaminski Tomasz S. , Colin Pierre-Yves , Hollfelder Florian
Published: February 2022

The recent massive release of new, man-made substances into the environment requires bioremediation, but a very limited number of enzymes evolved in response are available. When environments have not encountered the potentially hazardous materials in their evolutionary history, existing enzymes have to be repurposed. The recruitment of accidental, typically low-level promiscuous activities provides a head start that, after gene duplication, can adapt and provide a selectable advantage. This evolutionary scenario raises the question whether it is possible to adaptively improve the low-level activity of enzymes recruited from non- (or only recently) contaminated environments quickly to the level of evolved bioremediators.

Here we address the evolution of phosphotriesterases (enzymes for hydrolysis of organophosphate pesticides or chemical warfare agents) in such a scenario: In a previous functional metagenomics screening we had identified a promiscuous phosphotriesterase activity of the α/β-hydrolase P91, with an unexpected Cys-His-Asp catalytic triad as the active site motif. We now probe evolvability of P91 using ultrahigh-throughput screening in microfluidic droplets, and test for the first time whether the unique catalytic motif of a cysteine-containing triad can adapt to achieve rates that rival existing phosphotriesterases. These mechanistically distinct enzymes achieve their high rates based on catalysis involving a metal-ion cofactor. A focussed, combinatorial library of P91 (> 105 members) was screened on-chip in microfluidic droplets by quantification of the reaction product, fluorescein. Within only two rounds of evolution P91’s phosphotriesterase activity was increased ≈ 400-fold to a kcat/KM of ≈ 106 M−1s−1, matching the catalytic efficiencies of naturally evolved metal-dependent phosphotriesterases. In contrast to its homologue acetylcholinesterase that suffers suicide inhibition, P91 shows fast de-phosphorylation rates and is rate-limited by the formation of the covalent adduct rather than by its hydrolysis. Our analysis highlights how the combination of focussed, combinatorial libraries with the ultrahigh throughput of droplet microfluidics can be leveraged to identify and enhance mechanistic strategies that have not reached high efficiency in Nature, resulting in alternative reagents with a novel catalytic machinery.

GRAPHICAL ABSTRACT
A pili-driven bacterial turbine
Authors: Pönisch Wolfram , Zaburdaev Vasily
Published: February 2022

Work generated by self-propelled bacteria can be harnessed with the help of microdevices. Such nanofabricated microdevices, immersed in a bacterial bath, may exhibit unidirectional rotational or translational motion. Swimming bacteria that propel with the help of actively rotating flagella are a prototypical example of active agents that can power such microdevices.

In this work, we propose a computational model of a micron-sized turbine powered by bacteria that rely on active type IV pili appendages for surface-associated motility. We find that the turbine can rotate persistently over a time scale that significantly exceeds the characteristic times of the single cell motility. The persistent rotation is explained by the collective dynamics of multiple pili of groups of cells attaching to and pulling on turbine. Furthermore, we show that the turbine can rotate permanently in the same direction by altering the pili binding to the turbine surface in an asymmetric fashion. We thus can show that by changing the adhesive properties of the turbine while keeping its symmetric geometry, we can still break the symmetry of its rotation.

Altogether, this study widely expands the range of bacteria that can be used to power nanofabricated microdevices, and, due to high pili forces generated by pili retraction, promises to push the harnessed work by several orders of magnitude.
Feminine traits improve transformational leadership advantage: investigation of leaders’ gender traits, sex and their joint impacts on employee contextual performance
Authors: Chen Shu-Chen , Shao Jieqi
Published: February 2022

Purpose

This research aims to examine the indirect relationship between feminine traits and employee contextual performance through transformational leadership. Additionally, it explored the role of leaders’ sex in moderating the relationship between feminine traits and transformational leadership through a moderated mediation model that subsequently influences employee contextual performance.

Design/methodology/approach

This study tested and validated the moderated mediation model using a two-wave survey with 295 samples. Bootstrapping was adopted for model testing.

Findings

The results indicated that leaders’ sex moderated the relationship between feminine traits and employee contextual performance through transformational leadership, such that the indirect effect was stronger for female leaders than for male leaders.

Practical implications

Female leaders can improve employee contextual performance by demonstrating transformational leadership with feminine traits. Organizations must implement measures (i.e. training) to promote the acceptance and application of leader gender and gender-role trait diversity, reduce the prevalence of gender stereotypes and help leaders benefit from learning and implementing the effective combination of leadership and feminine traits.

Originality/value

The study demonstrated the joint effects of leaders’ sex (difference) and gender-role traits on employee contextual performance through transformational leadership. These results provide female leaders with feminine traits to gain a leadership advantage and an in-depth understanding of role congruity theory from the perspective of leadership effectiveness.
Self-efficacy and academic programme satisfaction: mediating effect of meaningfulness of study
Authors: Azila-Gbettor Edem M. , Mensah Christopher , Abiemo Martin Kwasi
Published: February 2022

Purpose

The paper examined the mediating effect of meaningfulness of study on the relation between self-efficacy and academic programme satisfaction within higher education setup.

Design/methodology/approach

A total of 376 randomly selected students took part in the study by completing a self-reported survey. Data were analysed using PLS-SEM.

Findings

Results suggest self-efficacy and meaningfulness of studies positively predict student's satisfaction with academic programme. Besides, meaningfulness of study mediates the relation between self-efficacy and student's satisfaction of academic programme.

Originality/value

This study is one of the first to provide empirical evidence of the influence of meaningfulness of studies on self-efficacy and student academic programme satisfaction in the higher education context.
Community engagement in development projects: government versus private funded projects in Ghana
Authors: Arkorful Helen , Hilton Sam Kris , Awaah Fred
Published: February 2022

Purpose

The abandonment of governmental development projects either after completion or midway completion at the taxpayer’s expense in Ghana could be attributed to lack of effective community engagement (CE). Thus, this study aims to assess CE in development projects by comparing government-sponsored projects to private-sponsored projects.

Design/methodology/approach

A qualitative approach was adopted where a multiple case study design was used as a research strategy. Data was collected from selected districts in the Central Region of Ghana by using a semi-structured interview guide and analyzed using the thematic and comparative analysis techniques.

Findings

The results reveal that CE in government-funded projects was low, while CE in projects funded by private organizations was high. Three levels of engagement (consultation, participation in decision-making and consent) were also identified. Furthermore, the roles of public participation, including knowledge sharing, collective sense of ownership, among others, were ascertained. Finally, resources constraints, competing interests, lack of information flow, public attitudes toward change and central government/political interference are challenges of CE in development projects.

Originality/value

This study has provided an empirical basis for government and other development agents to draft a policy on CE to serve as a guide, spell out the role of CE, mitigate the challenges of CE and ensure strict compliance to the three levels of engagement.
The association of dietary inflammatory index, functional foods and some antioxidants intake with COVID-19 vaccine side effects in Iranian adults
Authors: Mohajeri Mahsa
Published: February 2022

Purpose

This study aims to assess the association of dietary inflammatory index (DII), consumption of functional food and some antioxidants with COVID-19 vaccine side effects in Iranian adults.

Design/methodology/approach

This was a case–control study conducted among the 1,067 Iranian adults who were invited to participate through WhatsApp software. The dietary intake was assessed using the food frequency questionnaire.

Findings

There was a significant difference (p = 0.04) in vitamin D consumption between healthy people and persons with a vaccine side effect. Vitamin E intake in healthy participants was significantly (p = 0.04) more than case group. There was a significant difference in the consumption of zinc (p = 0.01), selenium (p = 0.02) and vitamin C (p = 0.02), between persons without vaccine side effects and the case group. Consumption of onion (82.5 ± 9.5 g/day vs 32.2 ± 6.3; p = 0.0001), garlic (6 ± 0.3 g/day vs 0.2 ± 0.08; p = 0.0001) and oat (2.2 ± 0.05 g/day vs 0.5 ± 0.01; p = 0.001) in the control group was significantly more than persons with vaccine side effects. With the increase in each unit in the score of the DII, the risk of COVID-19 vaccine side effect incidence increased 1.7 times (OR = 1.7; 95% CI: 1.3–1.8).

Originality/value

To the best of the authors’ knowledge, this study is the first that investigated the association between functional food intake and side effects of the COVID-19 vaccine.
To Test or Not to Test?: The Role of Testing in Elementary Social Studies A Collaborative Study Conducted by NCPSSE and SCPSSE
Authors: Heafner Tina L. , Lipscomb George B. , Rock Tracy C.
Published: February 2022

There are growing concerns among social studies professionals that social studies instruction is disappearing from elementary schools. These concerns have become more pressing as educational policies emphasize core curricula of reading, writing, mathematics, and science. Questions arise as to how social studies can resume its traditional role as one of these core curricula. One possibility is to have social studies included in the accountability movement through testing. This article contemplates the role of testing in impacting social studies instruction in the elementary curriculum through a comparative analysis of data collected from a study of practicing elementary teachers in two states: one in which social studies instruction is tested and the other in which social studies instruction is not tested.
Influences on Social Studies Teachers’ Issue-Selection for Classroom Discussion: Social Positioning and Media
Authors: Kaviani Khodadad (Khodi)
Published: February 2022

This qualitative research explores factors that influence social studies teachers’ issue-selection for classroom discussion. Four high school teachers—three from an urban setting and one from a suburban high school—participated in the study. Data were gathered over three months via interviews, classroom observations, and field notes; all were analyzed using the constant comparative technique of the grounded theory approach. Two claims are made: Teachers’ social positioning influences their curriculum choices, and media influences social studies teachers’ issue-selection.
Aware, Complacent, Discouraged, Empowered: Students’ Diverse Civic Identities
Authors: Rubin Beth C.
Published: February 2022

Based on a qualitative study of civic discourse in four distinct school settings, this article describes how students’ civic identities—the sense of who one is as an American citizen—are rooted in their experiences in particular schools and communities. Students’ developing civic identities vary from aware and empowered to complacent and discouraged, depending on their experiences both in and out of school. A civic education that taps into these experiences may be successful at creating a more active, engaged citizenry. This article describes a new understanding of youth civic identity and a problem-posing approach to civic education.
Strange Bedfellows: Censorship and History Textbooks
Authors: Matusevich Melissa N.
Published: February 2022

In spite of required state curriculum objectives, American history textbooks often become the de facto curriculum defining history. Self-imposed censorship by textbook publishers defines how individuals, groups, and events are portrayed. A 2004 Thomas B. Fordham Institute report concluded that today’s history textbooks are bland with no voice or storyline and have been sanitized and filled with history rewritten to meet the demands of special interest groups. The report also concluded that while American history textbooks now contain more pages, they include less content. Paradoxically, when a well-crafted textbook is created, students may never have access to it. Efforts by special interest groups to censor such books are not uncommon. A case study of one author’s efforts to have her award-winning history textbook adopted for classroom use and the ensuing censorship efforts by special interest groups are described.
A Learning Cycle Lesson Plan: Scale
Authors: Sunal Cynthia Szymanski , Sunal Dennis W. , Haas Mary E.
Published: February 2022

This learning cycle lesson plan uses hands-on and minds-on experiences to assist fourth or fifth graders in developing the important concept of scale. The lesson focuses on enabling students to define scale as a ratio so that one square represents more squares, e.g. 1:5. It also works to enable students to draw the same object in two different scales.
A Tale worth Telling: Helping Students Construct Stories of the Past
Authors: Gray Kimberly C. , Fridley Daryl E.
Published: February 2022

This article explores the clichéd notion of history as narrative. Within the context of an interesting narrative, events, ideas, and people in the past become plot points instead of detached fragments of data. This re-conception of historical facts as pieces of a story allows
Outcomes during delivery hospitalisations with inflammatory bowel disease
Authors: Yu K. , Faye A. S. , Wen T , Guglielminotti J. R. , Huang Y. , Wright J. D. , D’Alton M. E.  , Friedman A. M.
Published: February 2022

Objective

To characterise inflammatory bowel disease (IBD) trends and associated risk during delivery hospitalisations.

Design

Cross‐sectional.

Setting

US delivery hospitalisations.

Population

Delivery hospitalisations in the 2000–2018 National Inpatient Sample.

Methods

This study analysed a nationally representative hospital discharge database based on the presence of IBD. Temporal trends in IBD were analysed using joinpoint regression to estimate the average annual percent change (AAPC). IBD severity was characterised by the presence of diagnoses such as penetrating and stricturing disease and history of bowel resection. Risks for adverse outcomes were analysed based on presence of IBD. Poisson regression models were performed with unadjusted and adjusted risk ratios (aRR) as measures of effect.

Main Outcome Measure

Prevalence of IBD and associated adverse outcomes.

Results

Of 73 109 790 delivery hospitalisations, 89 965 had a diagnosis of IBD. IBD rose from 0.06% in 2000 to 0.21% in 2018 (AAPC 7.3%, 95% CI 6.7–7.9%). Among deliveries with IBD, IBD severity diagnoses increased from 4.1% to 8.1% from 2000 to 2018. In adjusted analysis, IBD was associated with increased risk for preterm delivery (aRR 1.50, 95% CI 1.47–1.53), severe maternal morbidity (aRR 1.93, 95% CI 1.83–2.04), venous thrombo‐embolism (aRR 2.76, 95% CI 2.39–3.18) and surgical injury during caesarean delivery hospitalisation (aRR 5.03, 95% CI 4.76–5.31). In the presence of a severe IBD diagnosis, risk was further increased for all adverse outcomes.

Conclusion

IBD is increasing in the obstetric population and is associated with adverse outcomes. Risk is increased in the presence of a severe IBD diagnosis.

Tweetable Abstract

Deliveries among women with inflammatory bowel disease are increasing. Disease severity is associated with adverse outcomes.
Second and third trimester estimation of gestational age using ultrasound or maternal symphysis‐fundal height measurements: A systematic review
Authors: Self Alice , Daher Lama , Schlussel Michael , Roberts Nia , Ioannou Christos , Papageorghiou Aris T.
Published: February 2022

Background

Accurate assessment of gestational age (GA) is important for managing pregnancies at an individual level and monitoring preterm birth rates at a population level.

Objectives

As many women first seek antenatal care in late pregnancy, our aim was to assess the methodology of studies reporting equations for estimating GA after 20 weeks’ gestation using ultrasound or symphysis‐fundal height (SFH) measurements.

Search strategy

Six electronic databases were searched for studies published from January 1970 to April 2021.

Selection criteria

Studies were included if they contained a formula using SFH or ultrasound‐measured biometry to estimate GA after 20 weeks in healthy singleton pregnancies.

Data collection and analysis

Two reviewers and a statistician reviewed study design, statistical methods, and reporting methods using 29 criteria. Each article was awarded an overall quality score, predefined as the percentage of the 29 criteria scored at low risk of bias. 95% prediction intervals were calculated for studies that used recommended first trimester dating to confirm true GA.

Main results

The search yielded 4209 results. Ninety‐seven full‐text articles were included in the analysis. The mean quality score was 32% (range 7%–97%). Only 10 articles scored low risk in 18 or more criteria. Their formulas estimated GA using one or more ultrasound‐measured biometry parameters and SFH measurements. Twenty‐three articles used recommended first trimester dating. A single‐parameter formula using transcerebellar diameter (TCD) gave the lowest 95% prediction interval.

Conclusions

There is considerable methodological heterogeneity in studies developing equations for estimating GA. Formulas using ultrasound‐based measurements more accurately estimated GA after 20 weeks than formulas using SFH measurement. While the clinical priority remains promotion of early engagement with antenatal care, we suggest unified standards for GA and growth assessment.

Tweetable abstract

Many vulnerable women seek antenatal care late in pregnancy. How should gestational age be determined? We examine all available studies estimating GA >20 weeks. Ultrasound is much better than fundal height, and using cerebellar measurement appears to be the most accurate.
What are the perspectives of speech pathologists, occupational therapists and physiotherapists on using telehealth videoconferencing for service delivery to children with developmental delays? A systematic review of the literature
Authors: Grant Claire , Jones Anne , Land Helen
Published: February 2022

Objective

To identify the attitudes and perspectives of speech pathologists, occupational therapists and physiotherapists on using telehealth videoconferencing for service delivery to children with developmental delays.

Design

Systematic Literature Review.

Method

An electronic search of databases Scopus, CINAHL, MEDLINE, PEDro, Speechbite, OTseeker and ScienceDirect was undertaken in October 2020. Articles were compared with eligibility criteria by 2 authors. All articles were appraised for quality and level of evidence.

Findings

Fourteen studies were deemed to be eligible. Results were synthesised using a narrative analysis. The themes identified were technology, self‐efficacy, replacement of face‐to‐face services, time management, relationships, access and family‐centred care. Each of these themes was seen as both a potential barrier and a facilitator when trying to provide services via telehealth.

Conclusions

The results in this review cannot be generalised due to small sampling size, low response rates, lack of maximum variation sampling and under‐representation of occupational therapists and physiotherapists. Study design was either mixed‐methods survey or interview or only survey or interview. Risk of bias in studies was high. Further research is required including comparison studies and cost‐benefit analysis.
Weight change during the first week of life and a new method for retrospective prediction of birthweight among exclusively breastfed newborns
Authors: Mtove George , Abdul Omari , Kullberg Fanny , Gesase Samwel , Scheike Thomas , Andersen Frederik Mølkjær , Madanitsa Mwayiwawo , ter Kuile Feiko O. , Alifrangis Michael , Lusingu John P. A. , Minja Daniel T. R. , Schmiegelow Christentze
Published: February 2022

Introduction

Identification of low birthweight and small for gestational age is pivotal in clinical management and many research studies, but in low‐income countries, birthweight is often unavailable within 24 h of birth. Newborn weights measured within days after birth and knowledge of the growth patterns in the first week of life can help estimate the weight at birth retrospectively. This study aimed to generate sex‐specific prediction maps and weight reference charts for the retrospective estimation of birthweight for exclusively breastfed newborns in a low‐resource setting.

Material and methods

This was a prospective cohort study nested in a clinical trial of intermittent preventive treatment in pregnancy for malaria with either dihydroartemisinin–piperaquine with/without azithromycin or sulfadoxine–pyrimethamine in Korogwe District, north‐eastern Tanzania (Clinicaltrials.gov: NCT03208179). Newborns were weighed at birth or in the immediate hours after birth and then daily for 1 week. Reference charts, nadir, time to regain weight, and prediction maps were generated using nonlinear mixed‐effects models fitted to the longitudinal data, incorporating interindividual variation as random effects. Predictions and prediction standard deviations were computed using a linear approximation approach.

Results

Between March and December 2019, 513 live newborns with birthweights measured within 24 h of delivery were weighed daily for 1 week. Complete datasets were available from 476 exclusively breastfed newborns. There was a rapid decline in weight shortly after delivery. The average weight loss, time of nadir, and time to regain weight were 4.3% (95% confidence interval [CI] 3.8–4.9) at 27 h (95% CI 24–30) and 105 h (95% CI 91–120) in boys and 4.9% (95% CI 4.2–5.6) at 28 h (95% CI 23–33) and 114 h (95% CI 93–136) in girls, respectively. The data were used to generate prediction maps with 1‐h time intervals and 0.05 kg weight increments showing the predicted birthweights and weight‐for‐age and weight‐change‐for‐age reference charts depicting variation in weight loss from <1 to >10%.

Conclusions

The prediction maps and reference charts can be used by researchers in low‐resource settings to retrospectively estimate birthweights using weights collected up to 168 h after delivery, thereby maximizing data utilization. Clinical practitioners can also use the prediction maps to retrospectively classify newborns as low birthweight or small for gestational age.
1,3‐diarylpyrazolones as potential anticancer agents for non‐small cell lung cancer: Synthesis and antiproliferative activity evaluation
Authors: Dahal Achyut , Lo Mary , Singh Sitanshu , Vo Huu , ElHage Denzel , Jois Seetharama D. , Murru Siva
Published: February 2022

A series of pyrazolone compounds with different substitution patterns have been synthesized using microwave‐assisted methods and evaluated their in vitro antiproliferative activity against human lung adenocarcinoma cell lines (A549 and NCI‐H522). Among the tested compounds, the pyrazolone P7 exhibited high antiproliferative activity against both A549 and NCIH522 cancer cell lines while being 10 times less cytotoxic to non‐cancerous cells. Moreover, our compounds P7 and P11 exhibited higher antiproliferative activity and selectivity against A549 and NCIH522 cells compared with the clinically approved drugs Afatinib and Gefitinib. The cell cycle analysis showed that the compound P7 and P11 arrests the cell cycle at G0/G1 phase, whereas the compounds P13 and P14 involved in G2/M phase arrest. The results from antiproliferative activity screening, cell cycle analysis, and kinase profiling indicate that the suitably substituted 1,3‐diarylpyrazolones exhibit high antiproliferative activity against non‐small cell lung cancer cells.
Newborn infant screening for spinal muscular atrophy: Chances and challenges
Authors: Mueller‐Felber Wolfgang
Published: February 2022

This commentary is on the original article by D’Silva et al. on pages 625–632 of this issue.
Praying the Imprecatory Psalms? Reflections on an Unresolved Theological Problem with Dietrich Bonhoeffer
Authors: Hamilton Nadine
Published: February 2022

This article probes the question of whether or not the so‐called imprecatory Psalms may be prayed either in private settings or churches. In his Finkenwalde sermon on Psalm 58, Dietrich Bonhoeffer considers them ‘the prayer[s] of the innocent’. This article examines Bonhoeffer’s understanding and handling of the imprecatory Psalms, which leads to the overall question of the theology of Scripture – in particular, the theological significance of the use of the Psalms as Christian prayer. This in turn leads to questions concerning the theological presuppositions, context, and implications of christological readings of the Old Testament, and last but not least the relationship between Scripture, incarnation and the cross. It is my argument that Bonhoeffer’s understanding of Jesus Christ is the hermeneutical key to Scripture. This must be elaborated in order to see how human prayer can also be the prayer of Jesus Christ at the same time. Only from there can one understand how, according to Bonhoeffer, in Christ the Christian can also pray the imprecatory Psalms.
Heterologous expression of a cryptic gene cluster from a marine proteobacterium Thalassomonas actiniarum affords new lanthipeptides thalassomonasins A and B
Authors: Thetsana Chanaphat , Ijichi Shinta , Kaweewan Issara , Nakagawa Hiroyuki , Kodani Shinya
Published: February 2022

Aims

The aim of this study was to utilize a cryptic biosynthetic gene cluster (BGC) of a marine proteobacterium Thalassomonas actiniarum for production of new lanthipeptides by heterologous expression system.

Methods and Results

Based on genome mining, a new BGC of class I lanthipeptide was found in the genome sequence of a marine proteobacterium T. actiniarum. Molecular cloning was performed to construct an expression vector derived from commercially available plasmid pET-41a(+). Heterologous production of new lanthipeptides named thalassomonasins A and B was performed using the host Escherichia coli BL21(DE3) harbouring the expression vector. The structure of thalassomonasin A was determined by the interpretation of NMR and MS data. As a result, thalassomonasin A was determined to be a lanthipeptide with three units of lanthionine. The bridging pattern of the lanthionine rings in thalassomonasin A was determined by interpretation of NOESY data. The structure of thalassomonasin B was proposed by MS/MS experiment.

Conclusions

We succeeded in heterologous production of new class I lanthipeptides using a BGC of a marine proteobacterium T. actiniarum.

Significance and Impact of the Study

To the best of our knowledge, this is the first report of heterologous production of lanthipeptides derived from proteobacterial origin. There are many cryptic biosynthetic gene clusters (BCGs) of this class of lanthipeptides in proteobacterial genomes. This study may lead to the production of new lanthipeptides by utilizing the BCGs.
Membrane traffic and Ca2+ signals in ciliates
Authors: Plattner Helmut
Published: February 2022

A Paramecium cell has as many types of membrane interactions as mammalian cells, as established with monoclonal antibodies by R. Allen and A. Fok. Since then, we have identified key players, such as SNARE proteins, Ca2+‐regulating proteins, including Ca2+‐channels, Ca2+‐pumps, Ca2+‐binding proteins of different affinity, etc., at the molecular level, probed their function and localized them at the light and electron microscopy level. SNARE proteins, in conjunction with a synaptotagmin‐like Ca2+‐sensor protein, mediate membrane fusion. This interaction is additionally regulated by monomeric GTPases whose spectrum in Tetrahymena and Paramecium has been established by A. Turkewitz. As known from mammalian cells, GTPases are activated on membranes in conjunction with lumenal acidification by an H+‐ATPase. For these complex molecules, we found in Paramecium an unsurpassed number of 17 a‐subunit paralogs which connect the polymeric head and basis part, V1 and V0. (This multitude may reflect different local functional requirements.) Together with plasmalemmal Ca2+‐influx channels, locally enriched intracellular InsP3‐type (InsP3R, mainly in osmoregulatory system) and ryanodine receptor‐like Ca2+‐release channels (ryanodine receptor‐like proteins, RyR‐LP), this complexity mediates Ca2+ signals for most flexible local membrane‐to‐membrane interactions. As we found, the latter channel types miss a substantial portion of the N‐terminal part. Caffeine and 4‐chloro‐meta‐cresol (the agent used to probe mutations of RyRs in man during surgery in malignant insomnia patients) initiate trichocyst exocytosis by activating Ca2+‐release channels type CRC‐IV in the peripheral part of alveolar sacs. This is superimposed by Ca2+‐influx, that is, a mechanism called “store‐operated Ca2+‐entry” (SOCE). For the majority of key players, we have mapped paralogs throughout the Paramecium cell, with features in common or at variance in the different organelles participating in vesicle trafficking. Local values of free Ca2+‐concentration, [Ca2+]i, and their change, for example, upon exocytosis stimulation, have been registered by flurochromes and chelator effects. In parallel, we have registered release of Ca2+ from alveolar sacs by quenched‐flow analysis combined with cryofixation and X‐ray microanalysis.
How does baseline anthropometry affect anthropometric outcomes in children receiving treatment for severe acute malnutrition? A secondary analysis of a randomized controlled trial
Authors: Dah Clarisse , Ourohire Millogo , Sié Ali , Ouédraogo Moussa , Bountogo Mamadou , Boudo Valentin , Lebas Elodie , Nyatigo Fanice , Arnold Benjamin F. , O'Brien Kieran S. , Oldenburg Catherine E.
Published: February 2022

Mid‐upper arm circumference (MUAC) < 11.5 cm and weight‐for‐height Z‐score (WHZ) < −3 are used for screening for severe acute malnutrition (SAM). Underweight and concurrent wasting and stunting may better target those at the highest risk of mortality. We compared anthropometric outcomes in children enrolled in a trial of antibiotics for SAM based on categories of baseline anthropometry, including indicators for programme admission (WHZ < −3, MUAC < 11.5) and alternative indicators (weight‐for‐age Z‐score [WAZ] < −3, concurrent wasting and stunting [WHZ < −3 and height‐for‐age Z‐score < −3]). Participants were followed weekly until nutritional recovery and at 8 weeks. We evaluated changes in weight gain (g/kg/day), MUAC, and WHZ in children admitted by admissions criteria (MUAC only, WHZ only, or MUAC and WHZ) and by underweight or concurrent wasting and stunting. Of 301 admitted children, 100 (33%) were admitted based on MUAC only, 41 (14%) WHZ only, and 160 (53%) both MUAC and WHZ, 210 (68%) were underweight and 67 (22%) were concurrently wasted/stunted. Low MUAC and low WHZ children had the lowest probability of nutritional recovery (17% vs. 50% for MUAC‐only and 34% for WHZ‐only). There was no difference in weight gain velocity or WHZ by admissions criteria (WHZ and/or MUAC). Underweight and concurrently wasted/stunted children had lower MUAC and WHZ at 8 weeks compared with those who were not underweight or concurrently wasted and stunted. Children with both low MUAC and low WHZ had the worst outcomes. Relying on MUAC alone may miss children who have poor outcomes. Other indicators, such as WAZ, may be useful for identifying vulnerable children.
CD47 promotes the proliferation and migration of adamantinomatous craniopharyngioma cells by activating the MAPK/ERK pathway, and CD47 blockade facilitates microglia‐mediated phagocytosis
Authors: Zhang Huarong , Wang Chaohu , Fan Jun , Zhu Qianchao , Feng Yiwen , Pan Jun , Peng Junxiang , Shi Jin , Qi Songtao , Liu Yi
Published: February 2022

Aims

CD47 is overexpressed in multiple tumours and plays an important role in immune escape and other biological processes of tumours. However, its role in adamantinomatous craniopharyngioma (ACP) remains unclear. Therefore, we explored the functions of CD47 in ACP.

Methods

In this study, the expression of CD47 and the infiltration of immune cells in ACP was determined by immunohistochemistry (IHC) or immunofluorescence. Microglia‐mediated phagocytosis was analysed using an in vitro phagocytosis assay. Using lentivirus transfection, CD47 was either silenced or overexpressed in primary ACP cells and the biological effects of CD47 on these cells were evaluated in vitro using cell viability, flow cytometry, wound healing, Transwell migration and 3D hydrogel assays. The protein expression levels were analysed by western blotting.

Results

Finger‐like protrusions, which may be the key factor in the recurrence of ACP, were primarily found in the region of hypothalamic involvement. The expression of CD47 was higher in palisading epithelium compared with stellate reticulum and epithelial whorls. An in vitro phagocytosis assay showed that CD47 blockade could promote microglia‐mediated phagocytosis. Functional assays revealed that CD47 promoted the growth, migration and invasion of ACP cells in vitro. Our mechanistic investigations showed that CD47 activated the MAPK/ERK pathway, thereby facilitating the biological behaviour of ACP cells.

Conclusions

Here, we demonstrated that CD47 plays an important role in ACP cells, suggesting that CD47 could be a new potential therapeutic target for ACP, and adding to the body of literature a role for the inhibition of MAPK/ERK in ACP.
All retinas are not created equal: Fovea‐to‐macula thickness ratio and foveal microvasculature in healthy young children
Authors: Demir Pelsin , Hovsepian Nathaniel , Pagels Peter , Petersson Vanja , Baskaran Karthikeyan , Macedo Antonio Filipe
Published: February 2022

Purpose

Markers for the relationships between structural and microvasculature measures given by optical coherence tomography angiography are necessary to increase the diagnostic and prognostic value of this technique. The aim of this study was to investigate relationships between structural and microvasculature measures around the fovea in healthy eyes of healthy children.

Methods

Observational cross‐sectional study involving children aged 8–17 years, born at full‐term, with no eye disease. The better of two 3 × 3 mm macular scans obtained with a Cirrus 5000HD‐OCT was analysed. Images were corrected for lateral magnification errors. Vessel density and perfusion were measured with ImageJ/Fiji software for the superficial capillary plexus. Structural measures including foveal and macular thicknesses were performed manually.

Results

The sample included 86 participants, 51 (59%) females. Mean age was 12.4 years (SD = 2.5); mean best‐corrected acuity was −0.10 logMAR (SD = 0.09); mean refractive error was +0.59 D (SD = 1.3) and mean axial length was 23.1 mm (SD = 0.86). Mean area of the foveal avascular zone (AFAZ) was 0.20 mm2 (SD = 0.88); median fovea‐to‐macula thickness ratio (FMTR) was 0.63 (IQR = 0.08); mean central vessel density was 12.42 mm−1 (SD = 2.78) and mean central perfusion was 38.66% (SD = 3.83). AFAZ was correlated with central vessel density (p < 0.001), perfusion (p < 0.001), foveal thickness (p < 0.001) and FMTR (p < 0.001). Central vessel density was correlated with foveal thickness (p < 0.001) and FMTR, (p = 0.01). Central perfusion was correlated with foveal thickness (p < 0.001) and FMTR, (p = 0.003).

Conclusion

In this study, foveal thickness, FMTR and foveal microvasculature measurements were correlated. Clinicians need to be aware that shallow foveal pits and persistent foveal microvasculature are likely to occur in optical coherence tomography angiography images. In healthy eyes from healthy children, an atypical high FMTR and a small AFAZ may be associated with incomplete foveal development. The mechanism and functional implications of this remain unknown.
MAIA microperimeter for short‐duration fixation stability measurements in central vision loss: Repeatability and comparison with the Nidek MP1
Authors: Pyatova Yulia , Markowitz Samuel N , Devenyi Robert G , Tarita‐Nistor Luminita
Published: February 2022

Purpose

This study reports the repeatability of 20 s‐duration fixation stability measurements recorded with the Macular Integrity Assessment (MAIA) microperimeter in patients with central vision loss, in contrast to the Nidek MP1 microperimeter.

Methods

Fixation stability was recorded in 39 eyes of 25 patients with macular disease using MAIA and the MP1 for 20 s intervals, twice for each eye, with each instrument. Twenty eyes were identified as the better eye (BE) and 19 eyes as the worse eye (WE). Fixation stability was quantified with the 95% bivariate contour ellipse area (BCEA), logarithmically transformed. Bland‐Altman plots were used to determine the 95% limits of agreement.

Results

For MAIA, the 95% limits of agreement were ±0.84 log deg2 for the BE and ±0.66 log deg2 for the WE. Similarly, for the MP1 these limits were ±0.48 log deg2 for the BE and ±0.72 log deg2 for the WE. Inter‐device repeatability was modest, ±1.09 log deg2 for the BE and ±1.01 log deg2 for the WE, and a proportional bias was detected. Occasionally, MAIA did not register all the expected number of data points, and included far outliers in the BCEA calculation; the inter‐device repeatability did not improve when these outliers were removed.

Conclusions

Repeatability of 20 s‐duration fixation stability examination in patients with central vision loss is specific to the instrument used. We recommend that only data from same type of microperimeter with the same fixation duration should be compared when using fixation stability as an outcome measure to monitor disease progression, effect of treatment or in clinical trials.