bluuebunny/crossref_metadata_2025 huggingface dataset:
Lifting weak lensing degeneracies with a field-based likelihood
Authors: Porqueres Natalia , Heavens Alan , Mortlock Daniel , Lavaux Guilhem
Published: November 2021

We present a field-based approach to the analysis of cosmic shear data to infer jointly cosmological parameters and the dark matter distribution. This forward modelling approach samples the cosmological parameters and the initial matter fluctuations, using a physical gravity model to link the primordial fluctuations to the non-linear matter distribution. Cosmological parameters are sampled and updated consistently through the forward model, varying (1) the initial matter power spectrum, (2) the geometry through the distance-redshift relationship, and (3) the growth of structure and light-cone effects. Our approach extracts more information from the data than methods based on two-point statistics. We find that this field-based approach lifts the strong degeneracy between the cosmological matter density, Ωm, and the fluctuation amplitude, σ8, providing tight constraints on these parameters from weak lensing data alone. In the simulated four-bin tomographic experiment we consider, the field-based likelihood yields marginal uncertainties on σ8 and Ωm that are, respectively, a factor of 3 and 5 smaller than those from a two-point power spectrum analysis applied to the same underlying data.
Dark Energy Camera photometry reveals extra-tidal stars around the Milky Way globular cluster NGC 6864 (M75)
Authors: Piatti Andrés E
Published: November 2021

Globular clusters are prone to lose stars while moving around the Milky Way. These stars escape the clusters and are distributed throughout extended envelopes or tidal tails. However, such extra-tidal structures are not observed in all globular clusters, and yet there are no structural or dynamical parameters that can predict their presence or absence. NGC 6864 is an outer halo globular cluster with reported no observed tidal tails. We used Dark Energy Camera photometry reaching ∼4 mag underneath its main-sequence turnoff to confidently detect an extra-tidal envelope, and stellar debris spread across the cluster outskirts. These features emerged once robust field star filtering techniques were applied to the fainter end of the observed cluster main sequence. NGC 6864 is associated to the Gaia-Enceladus dwarf galaxy, among others 28 globular clusters. Up-to-date, nearly 64${{\ \rm per\,cent}}$ of them have been targeted looking for tidal tails and most of them have been confirmed to exhibit tidal tails. Thus, the present outcomes allow us to speculate on the possibility that Gaia-Enceladus globular clusters share a common pattern of mass loss by tidal disruption.
A deep radio view of the evolution of the cosmic star formation rate density from a stellar-mass-selected sample in VLA-COSMOS
Authors: Malefahlo Eliab D , Jarvis Matt J , Santos Mario G , White Sarah V , Adams Nathan J , Bowler Rebecca A A
Published: November 2021

We present the 1.4 GHz radio luminosity functions (RLFs) of galaxies in the Cosmic Evolution Survey (COSMOS) field, measured above and below the 5σ detection threshold, using a Bayesian model-fitting technique. The radio flux densities from Very Large Array (VLA)-COSMOS 3-GHz data are extracted at the position of stellar-mass-selected galaxies. We fit a local RLF model, which is a combination of active galactic nuclei and star-forming galaxies (SFGs), in 10 redshift bins with a pure luminosity evolution model. Our RLF exceeds previous determinations at low radio luminosities at z < 1.6 with the same radio data, due to our ability to directly constrain the knee and faint-end slope of the RLF. Beyond z ∼ 2, we find that the SFG part of the RLF exhibits a negative evolution (L* moves to lower luminosities) due to the decrease in low stellar-mass galaxies in our sample at high redshifts. From the RLF for SFGs, we determine the evolution in the cosmic star formation rate density (SFRD), which we find to be consistent with the established behaviour up to z ∼ 1 using far-infrared data, but exceeds that from the previous radio-based work for the reasons highlighted above. Beyond z ∼ 1.5 the cosmic SFRD declines. We note that the relation between radio luminosity and star formation rate is crucial in measuring the cosmic SFRD from radio data at z > 1.5. We investigate the effects of stellar mass on the total RLF by splitting our sample into low (108.5 ≤ M/M⊙ ≤ 1010) and high ($M\gt 10^{10}\, \mathrm{M}_{\odot }$) stellar-mass subsets. We find that the SFRD is dominated by sources in the high stellar masses bin, at all redshifts.
Histone H3K27 Methylation Perturbs Transcriptional Robustness and Underpins Dispensability of Highly Conserved Genes in Fungi
Authors: Moser Tralamazza Sabina , Nanchira Abraham Leen , Reyes-Avila Claudia Sarai , Corrêa Benedito , Croll Daniel
Published: November 2021

Epigenetic modifications are key regulators of gene expression and underpin genome integrity. Yet, how epigenetic changes affect the evolution and transcriptional robustness of genes remains largely unknown. Here, we show how the repressive histone mark H3K27me3 underpins the trajectory of highly conserved genes in fungi. We first performed transcriptomic profiling on closely related species of the plant pathogen Fusarium graminearum species complex. We determined transcriptional responsiveness of genes across environmental conditions to determine expression robustness. To infer evolutionary conservation, we used a framework of 23 species across the Fusarium genus including three species covered with histone methylation data. Gene expression variation is negatively correlated with gene conservation confirming that highly conserved genes show higher expression robustness. In contrast, genes marked by H3K27me3 do not show such associations. Furthermore, highly conserved genes marked by H3K27me3 encode smaller proteins, exhibit weaker codon usage bias, higher levels of hydrophobicity, show lower intrinsically disordered regions, and are enriched for functions related to regulation and membrane transport. The evolutionary age of conserved genes with H3K27me3 histone marks falls typically within the origins of the Fusarium genus. We show that highly conserved genes marked by H3K27me3 are more likely to be dispensable for survival during host infection. Lastly, we show that conserved genes exposed to repressive H3K27me3 marks across distantly related Fusarium fungi are associated with transcriptional perturbation at the microevolutionary scale. In conclusion, we show how repressive histone marks are entangled in the evolutionary fate of highly conserved genes across evolutionary timescales.
45S rDNA Repeats of Turtles and Crocodiles Harbor a Functional 5S rRNA Gene Specifically Expressed in Oocytes
Authors: Davidian Asya G , Dyomin Alexander G , Galkina Svetlana A , Makarova Nadezhda E , Dmitriev Sergey E , Gaginskaya Elena R
Published: November 2021

In most eukaryotic genomes, tandemly repeated copies of 5S rRNA genes are clustered outside the nucleolus organizer region (NOR), which normally encodes three other major rRNAs: 18S, 5.8S, and 28S. Our analysis of turtle rDNA sequences has revealed a 5S rDNA insertion into the NOR intergenic spacer in antisense orientation. The insertion (hereafter called NOR-5S rRNA gene) has a length of 119 bp and coexists with the canonical 5S rDNA clusters outside the NOR. Despite the ∼20% nucleotide difference between the two 5S gene sequences, their internal control regions for RNA polymerase III are similar. Using the turtle Trachemys scripta as a model species, we showed the NOR-5S rDNA specific expression in oocytes. This expression is concurrent with the NOR rDNA amplification during oocyte growth. We show that in vitellogenic oocytes, the NOR-5S rRNA prevails over the canonical 5S rRNA in the ribosomes, suggesting a role of modified ribosomes in oocyte-specific translation. The orders Testudines and Crocodilia seem to be the only taxa of vertebrates with such a peculiar rDNA organization. We speculate that the amplification of the 5S rRNA genes as a part of the NOR DNA during oogenesis provides a dosage balance between transcription of all the four ribosomal RNAs while producing a maternal pool of extra ribosomes. We further hypothesize that the NOR-5S rDNA insertion appeared in the Archelosauria clade during the Permian period and was lost later in the ancestors of Aves.
IID 2021: towards context-specific protein interaction analyses by increased coverage, enhanced annotation and enrichment analysis
Authors: Kotlyar Max , Pastrello Chiara , Ahmed Zuhaib , Chee Justin , Varyova Zofia , Jurisica Igor
Published: November 2021

Improved bioassays have significantly increased the rate of identifying new protein-protein interactions (PPIs), and the number of detected human PPIs has greatly exceeded early estimates of human interactome size. These new PPIs provide a more complete view of disease mechanisms but precise understanding of how PPIs affect phenotype remains a challenge. It requires knowledge of PPI context (e.g. tissues, subcellular localizations), and functional roles, especially within pathways and protein complexes. The previous IID release focused on PPI context, providing networks with comprehensive tissue, disease, cellular localization, and druggability annotations. The current update adds developmental stages to the available contexts, and provides a way of assigning context to PPIs that could not be previously annotated due to insufficient data or incompatibility with available context categories (e.g. interactions between membrane and cytoplasmic proteins). This update also annotates PPIs with conservation across species, directionality in pathways, membership in large complexes, interaction stability (i.e. stable or transient), and mutation effects. Enrichment analysis is now available for all annotations, and includes multiple options; for example, context annotations can be analyzed with respect to PPIs or network proteins. In addition to tabular view or download, IID provides online network visualization. This update is available at http://ophid.utoronto.ca/iid.
SwissBioisostere 2021: updated structural, bioactivity and physicochemical data delivered by a reshaped web interface
Authors: Cuozzo Alessandro , Daina Antoine , Perez Marta A S , Michielin Olivier , Zoete Vincent
Published: November 2021

At several stages of drug discovery, bioisosteric replacement is a common and efficient practice to find new bioactive chemotypes or to optimize series of molecules toward drug candidates. The critical steps consisting in selecting which molecular moiety should be replaced by which other chemical fragment is often relying on the expertise of specialists. Nowadays, valuable support can be obtained through the wealth of dedicated structural and knowledge data. The present article details the update of SwissBioisostere, a database of >25 millions of unique molecular replacements with data on bioactivity, physicochemistry, chemical and biological contexts extracted from the literature and related resources. The content of the database together with analysis and visualization capacities is freely available at www.swissbioisostere.ch.
ConsensusPathDB 2022: molecular interactions update as a resource for network biology
Authors: Kamburov Atanas , Herwig Ralf
Published: November 2021

Molecular interactions are key drivers of biological function. Providing interaction resources to the research community is important since they allow functional interpretation and network-based analysis of molecular data. ConsensusPathDB (http://consensuspathdb.org) is a meta-database combining interactions of diverse types from 31 public resources for humans, 16 for mice and 14 for yeasts. Using ConsensusPathDB, researchers commonly evaluate lists of genes, proteins and metabolites against sets of molecular interactions defined by pathways, Gene Ontology and network neighborhoods and retrieve complex molecular neighborhoods formed by heterogeneous interaction types. Furthermore, the integrated protein–protein interaction network is used as a basis for propagation methods. Here, we present the 2022 update of ConsensusPathDB, highlighting content growth, additional functionality and improved database stability. For example, the number of human molecular interactions increased to 859 848 connecting 200 499 unique physical entities such as genes/proteins, metabolites and drugs. Furthermore, we integrated regulatory datasets in the form of transcription factor–, microRNA– and enhancer–gene target interactions, thus providing novel functionality in the context of overrepresentation and enrichment analyses. We specifically emphasize the use of the integrated protein–protein interaction network as a scaffold for network inferences, present topological characteristics of the network and discuss strengths and shortcomings of such approaches.
Cellular heterogeneity in DNA alkylation repair increases population genetic plasticity
Authors: Vincent Maxence S , Uphoff Stephan
Published: November 2021

DNA repair mechanisms fulfil a dual role, as they are essential for cell survival and genome maintenance. Here, we studied how cells regulate the interplay between DNA repair and mutation. We focused on the adaptive response that increases the resistance of Escherichia coli cells to DNA alkylation damage. Combination of single-molecule imaging and microfluidic-based single-cell microscopy showed that noise in the gene activation timing of the master regulator Ada is accurately propagated to generate a distinct subpopulation of cells in which all proteins of the adaptive response are essentially absent. Whereas genetic deletion of these proteins causes extreme sensitivity to alkylation stress, a temporary lack of expression is tolerated and increases genetic plasticity of the whole population. We demonstrated this by monitoring the dynamics of nascent DNA mismatches during alkylation stress as well as the frequency of fixed mutations that are generated by the distinct subpopulations of the adaptive response. We propose that stochastic modulation of DNA repair capacity by the adaptive response creates a viable hypermutable subpopulation of cells that acts as a source of genetic diversity in a clonal population.
Constrained peptides mimic a viral suppressor of RNA silencing
Authors: Kuepper Arne , McLoughlin Niall M , Neubacher Saskia , Yeste-Vázquez Alejandro , Collado Camps Estel , Nithin Chandran , Mukherjee Sunandan , Bethge Lucas , Bujnicki Janusz M , Brock Roland , Heinrichs Stefan , Grossmann Tom N
Published: November 2021

The design of high-affinity, RNA-binding ligands has proven very challenging. This is due to the unique structural properties of RNA, often characterized by polar surfaces and high flexibility. In addition, the frequent lack of well-defined binding pockets complicates the development of small molecule binders. This has triggered the search for alternative scaffolds of intermediate size. Among these, peptide-derived molecules represent appealing entities as they can mimic structural features also present in RNA-binding proteins. However, the application of peptidic RNA-targeting ligands is hampered by a lack of design principles and their inherently low bio-stability. Here, the structure-based design of constrained α-helical peptides derived from the viral suppressor of RNA silencing, TAV2b, is described. We observe that the introduction of two inter-side chain crosslinks provides peptides with increased α-helicity and protease stability. One of these modified peptides (B3) shows high affinity for double-stranded RNA structures including a palindromic siRNA as well as microRNA-21 and its precursor pre-miR-21. Notably, B3 binding to pre-miR-21 inhibits Dicer processing in a biochemical assay. As a further characteristic this peptide also exhibits cellular entry. Our findings show that constrained peptides can efficiently mimic RNA-binding proteins rendering them potentially useful for the design of bioactive RNA-targeting ligands.
Trophic niche partitioning of three larval Sciaenidae species in the north-western Gulf of Mexico
Authors: Mcaskill Shannan , Paxton Stormy , Geist Simon J
Published: November 2021

The ability of larval fish to find prey items in sufficient quantities plays an important role in determining survivorship. To understand trophic niche partitioning and the potential for competition, we analyzed morphology and digestive tract content in larvae of three co-occurring, sciaenid fish species: Cynoscion nothus, Larimus fasciatus and Micropogonias undulatus. Larvae were collected in the north-western Gulf of Mexico off Galveston, TX, at seven stations in October/November 2017. Intra- and interspecific diet composition was analyzed between three ontogenetic development stages and two sampling zones (nearshore vs mid-shelf). M. undulatus had a significantly smaller mouth size than the other two species and consumed smaller prey items compared with C. nothus. Copepoda dominated all larval diets. The highly abundant M. undulatus primarily ate Calanoida following typical Sciaenidae feeding preferences. The less abundant C. nothus and L. fasciatus shared Cyclopoida as a primary diet item but differed in the consumption of less important prey taxa (i.e. Ostracoda, Chaetognatha). Ontogenetic dietary shifts (ODSs) were observed for all species, with the timing and number of ODS differing for C. nothus between sampling zones. The inclusion of alternative food sources such as Cyclopoida and non-copepod prey taxa likely alleviated potential interspecific competition allowing for larval co-occurrence.
The perception of stakeholders on the applicability of nurse-led clinics in the management of rheumatoid arthritis
Authors: Doumen Michaël , Westhovens René , Vandeputte Maryline , Van Melder Rani , Van der Elst Kristien , Pazmino Sofia , Bertrand Delphine , Stouten Veerle , Van Laeken Els , Creten Nelly , Neys Claudia , Verschueren Patrick , De Cock Diederik
Published: November 2021

Objectives

RA should be treated to target in a process of shared decision-making with patients. Person-centred care is essential to meeting specific patient needs. Nurse-led clinics, where a nurse is responsible for care, have demonstrated added value in some countries but are still not implemented widely. This study aimed to explore stakeholders’ perceptions of advantages, disadvantages and conditions for the implementation of nurse-led clinics for RA in Belgium.

Methods

We performed a cross-sectional qualitative study consisting of five semi-structured focus group interviews. Rheumatology nurses, patients with RA and rheumatologists were interviewed as stakeholders. The analysis was carried out by three researchers according to the Qualitative Analysis Guide of Leuven (QUAGOL), formulating a conceptual framework of overarching themes and deconstructing this into perceived advantages, disadvantages and conditions.

Results

Two focus groups with nurses (total n = 16), two with patients (n = 17) and one with rheumatologists (n = 9) were conducted. The interview synthesis resulted in five overarching themes across stakeholders: efficiency of care, disease management, legal and organizational requirements, the conventional role of the nurse and the extended role of the nurse. All stakeholders perceived additional education for nurses as essential, but rheumatologists debated nurses’ abilities to lead a rheumatology clinic. Furthermore, patients preferred care protocols to guide nurses, and care providers approached this reluctantly. Generally, patients with a well-controlled disease were perceived as the ideal candidates for nurse-led care.

Conclusion

Nurse-led clinics could provide many benefits but require additional nurse education and a legal and organizational framework before being implemented widely and successfully.
Clinical profile and treatment outcomes in antisynthetase syndrome: a tertiary centre experience
Authors: Sreevilasan Sreejitha Kodakkattil , Devarasetti Phanikumar , Narahari Narendra Kumar , Desai Anitha , Rajasekhar Liza
Published: November 2021

Objectives

The aim was to describe the clinical profile and outcomes in patients with antisynthetase syndrome (ASS) from a tertiary care centre.

Methods

The clinical data and investigations of all patients classified as ASS by Connors criteria over 5 years were recorded, and they were followed up prospectively. The median (interquartile range) was used for descriptive statistics. Clinical variables between the Jo-1 and non-Jo-1 groups and between patients with and without anti-Ro52 antibodies were compared using the χ2 test. Survival analysis was done using the log rank test.

Results

The 28 patients (23 females) had a median age of 42.5 (34.8–52.3) years, with a disease duration of 1.75 (0.6–3.8) years at diagnosis, and had a follow-up of 2 (0.25–4.25) years. Seronegative arthritis was seen in 23 of 28 patients. Non-specific interstitial pneumonia was seen in 19 patients with interstitial lung disease (ILD). Antibodies to Jo-1 (n = 17) were more frequent than non-Jo-1 antibodies (n = 11; five anti-PL-12, four anti-PL-7 and two anti-EJ). There was no significant difference in the prevalence of myositis (P = 0.07) or ILD (P = 0.11) between groups. Anti-Ro52 antibodies were more frequently found in the non-Jo-1 group (P = 0.006, ϕ = 0.51). A partial or complete improvement with treatment was seen in three-quarters of the patients. Five patients succumbed to the illness. Better survival was seen in the Jo-1 group (P = 0.05).

Conclusion

The most typical presenting manifestation of ASS in our cohort was isolated seronegative arthritis. Non-specific interstitial pneumonia was the commonest ILD pattern. Patients with antibodies to Jo-1 had better survival compared with non-Jo-1. The non-Jo-1 aminoacyl-transfer RNA synthetases had a strong association with anti-Ro52 antibodies.
Human carbamylome description identifies carbamylated α2-macroglobulin and hemopexin as two novel autoantigens in early rheumatoid arthritis
Authors: Sidiras Paschalis , Lechanteur Jessica , Imbault Virginie , Sokolova Tatiana , Durez Patrick , Gangji Valérie , Communi David , Rasschaert Joanne
Published: November 2021

Objectives

Anti-carbamylated protein antibodies (anti-CarPAs) are present in RA sera and have been associated with erosive disease. The exact targets of anti-CarPAs in vivo are currently not well known; we used a proteomic approach on serum and SF of RA patients to assess the human carbamylome and to identify carbamylated autoantigens as potential biomarkers in early RA.

Methods

Mass spectrometry was performed on SF and serum from RA patients. Carbamylated proteins present in both sample types were selected as candidate autoantigens for the establishment of ELISAs. A cohort of early RA patients was tested for positivity for specific anti-CarPAs.

Results

Eleven novel carbamylated proteins were identified, and five were selected as potential autoantigens for detection of anti-CarPAs. Among them, antibodies against carbamylated hemopexin (anti-CaHPX) and alpha-2-macroglobulin (anti-CaA2M) showed comparable diagnostic value to the established carbamylated foetal calf serum–based ELISA. A cohort of 189 early RA patients was studied. The combination of these new biomarkers with anti-citrullinated protein antibodies and RF identified 89% of early RA patients in our cohort. There was little correlation between the tested biomarkers, and each one of the tested antigens could identify a different subset of seronegative RA patients. Anti-CaA2M positivity showed clinical potential, being associated with higher disease disability.

Conclusion

We highlight the detection of novel carbamylated autoantigens in vivo using a combined proteomics approach in the SF and serum of RA patients. Anti-CaHPX and anti-CaA2M are promising clinical biomarkers, especially in seronegative RA.
Altruistic acting caused by a touching hand: neural underpinnings of the Midas touch effect
Authors: Schaefer Michael , Kühnel Anja , Rumpel Franziska , Gärtner Matti
Published: November 2021

Giving and receiving touch are some of the most important social stimuli we exchange in daily life. By touching someone, we can communicate various types of information. Previous studies have also demonstrated that interpersonal touch may affect our altruistic behavior. A classic study showed that customers give bigger tips when they are lightly touched by a waitress, which has been called the Midas touch effect. Numerous studies reported similar effects of touch on different kinds of helping or prosocial behaviors. Here, we aim to examine the neural underpinnings of this effect by employing a functional magnetic resonance imaging approach. While lying in the scanner, participants played different rounds of the dictator game, a measure of prosocial behavior. Before each round, participants were touched (or not touched in the control condition) by an experimenter. We found that touching the hand increased the likeliness to behave prosocial (but not the general liking of control stimuli), thereby confirming the Midas touch effect. The effect was predicted by activity in the primary somatosensory cortex, indicating that the somatosensory cortex here plays a causal role in prosocial behavior. We conclude that the tactile modality in social life may be much more important than previously thought.
Sleep-disordered breathing is frequently associated with idiopathic normal pressure hydrocephalus but not other types of hydrocephalus
Authors: Riedel Casper Schwartz , Milan Joachim Birch , Juhler Marianne , Jennum Poul
Published: November 2021

Study Objectives

Previous studies have shown sleep-disordered breathing (SDB) to be highly prevalent in patients with idiopathic normal pressure hydrocephalus (iNPH). The current study aimed to estimate and compare the prevalence of SDB in patients with different types of hydrocephalus and test if SDB was associated with changed CO2.

Methods

We investigated the prevalence of SDB in a prospective cohort of 48 hydrocephalus patients with nocturnal polysomnography (PSG). Twenty-three of the patients also had simultaneous CO2 measurements.

Results

The prevalence of SDB was high in patients with iNPH, with moderate-to-severe SDB in 21/22 (96%) of the patients and an apnea-hypopnea index (AHI) of 43.5 (95% CI 33.8–52.2). Patients with pediatric-onset hydrocephalus had moderate-to-severe SDB in 7/16 (44%), with an AHI of 16.1 (95% CI 8.16–23.8). Except for one patient, all patients with adult-onset obstructive hydrocephalus (9/10) had normal respiration or mild SDB with an AHI of 8.4 (95% CI 5.5–10.5). None of the 23 patients measured with CO2 had elevated CO2 associated with SDB and had normal CO2 during sleep, with 40.8 ± 5.5 mmHg, 42.7 ± 4.1 mmHg, 34.5–45.8 mmHg for patients with iNPH, pediatric-onset, and adult-onset, respectively.

Conclusion

We found a high prevalence of SDB in patients with iNPH, confirming previous findings. We extended this with the finding that the prevalence of SDB in patients with other types of hydrocephalus is not significantly different from that in the general population. Additionally, we did not find elevations of CO2 associated with SDB or CO2 retention during sleep.
The Future of Uncertainty Factors With In Vitro Studies Using Human Cells
Authors: Dourson Michael , Ewart Lorna , Fitzpatrick Suzanne C , Barros Silvia B M , Mahadevan Brinda , Hayes A Wallace
Published: November 2021

New approach methodologies (NAMs), including in vitro toxicology methods such as human cells from simple cell cultures to 3D and organ-on-a-chip models of human lung, intestine, liver, and other organs, are challenging the traditional “norm” of current regulatory risk assessments. Uncertainty Factors continue to be used by regulatory agencies to account for perceived deficits in toxicology data. With the expanded use of human cell NAMs, the question “Are uncertainty factors needed when human cells are used?” becomes a key topic in the development of 21st-century regulatory risk assessment. M.D., PhD, the coauthor of an article detailing uncertainty factors within the U.S. EPA, and L.E., PhD., Executive Vice President, Science, Emulate, who is involved in developing organ-on-a-chip models, debated the topic. One important outcome of the debate was that in the case of in vitro human cells on a chip, the interspecies (animal to human) uncertainty factor of 10 could be eliminated. However, in the case of the intraspecies (average human to sensitive human), the uncertainty factor of 10, additional toxicokinetic and/or toxicodynamic data or related information will be needed to reduce much less eliminate this factor. In the case of other currently used uncertainty factors, such as lowest observable adverse effect level to no-observed adverse effect level extrapolation, missing important toxicity studies, and acute/subchronic to chronic exposure extrapolation, additional data might be needed even when using in vitro human cells. Collaboration between traditional risk assessors with decades of experience with in vivo data and risk assessors working with modern technologies like organ chips is needed to find a way forward.
Feto-Maternal Outcomes of Breastfeeding during Pregnancy: A Systematic Review and Meta-Analysis
Authors: Minh Le Huu Nhat , Tawfik Gehad Mohamed , Ghozy Sherief , Hashan Mohammad Rashidul , Nam Nguyen Hai , Linh Le Khac , Abdelrahman Sara Attia Mahmoud , Quynh Tran Thuy Huong , Khoi Quan Nguyen , Nhat Le Tran , Ibrahim Hassan Yousif , El-Nile Mohamed Omar , Kamel Ahmed Mostafa Ahmed , Giang Hoang Thi Nam , Huy Nguyen Tien
Published: November 2021

Background

Breastfeeding is beneficial to both mother and infant. However, overlap of lactation with pregnancy and short recuperative intervals may impact mothers nutritionally. We aimed to investigate the possible effects of pregnancy during breastfeeding.

Methods

In October 2018, we searched systematically in nine electronic databases to investigate any association of breastfeeding during pregnancy with fetal and/or maternal outcomes. The study protocol was registered in PROSPERO (CRD41017056490). A meta-analysis was done to detect maternal and fetal outcomes and complications during pregnancy. Quality assessment was performed using the Australian Cancer Council bias tool for included studies.

Results

With 1992 studies initially identified, eight were eligible for qualitative analysis and 12 for quantitative analysis. Our results showed no significant difference in different abortion subtypes between lactating and non-lactating ones. In delivery, no difference between two groups regarding the time of delivery in full-term healthy, preterm delivery and preterm labor. No significant difference was detected in rates of antepartum, postpartum hemorrhage and prolonged labor between two groups. The women with short reproductive intervals may have higher supplemental intake and greater reduction fat store. The present studies showed that breastfeeding during pregnancy does not lead to adverse outcomes in the mother and her fetus in normal low-risk pregnancy, although it may lead to the nutritional burden on the mother.

Conclusion

The present studies showed that breastfeeding during pregnancy did not lead to the adverse outcomes in the mother and her fetus.
Drug Resistance in Children with Central Nervous System Tuberculosis from a Tertiary Care Center in Mumbai
Authors: Mane Sushant S , Janardhanan Jyothi , Pustake Manas , Ali Mohammed Kashif , Khan Gazi Israil
Published: November 2021

Introduction

Central Nervous System tuberculosis (CNS-TB) is the most lethal form of extra-pulmonary TB, especially in children. In this study, we have discussed patterns of drug resistance in pediatric CNS-TB.

Materials and Methods

Prospective observational study conducted on 100 children at a tertiary care center. Diagnosed cases of CNS-TB were enrolled. GeneXpert MTB/RIF was used upfront for diagnosis, and in cases where TB MGIT culture was positive, a phenotypic Drug Susceptibility Test (DST) was done. Patients were divided into resistant to at least one drug (DR) and drug-susceptible (DS). Various parameters were compared between these groups.

Results

Mean age of participants was 5.84 ± 3.5 years, with a male-to-female ratio of 1.08 : 1; 14% of children had drug-resistant CNS TB (DR-CNS-TB). A higher proportion of children previously treated for TB were associated with drug resistance (p = 0.009), and those with disseminated TB also had a higher drug resistance (p = 0.002). Apart from this, the DR and DS groups had no statistically significant differences in demographic, clinical or epidemiological parameters.

Conclusions

Previous history of being treated for TB and disseminated TB was an independent risk factor for DR-CNS-TB. Ensuring proper adherence and compliance to anti-tubercular treatment could help in preventing the emergence of DR TB.
Loop-Mediated Isothermal Amplification for Rapid Detection of Mating Types of Villosiclava virens
Authors: Pan Xiayan , Wang Xiao , Yu Junjie , Yu Mina , Cao Huijuan , Yong Mingli , Song Tianqiao , Qi Zhongqiang , Du Yan , Zhang Rongsheng , Liu Yongfeng
Published: November 2021

Rice false smut (RFS), caused by Villosiclava virens, is an important fungal disease in panicles of rice. V. virens is a heterothallic ascomycete controlled by two opposite idiomorphs, MAT1-1 and MAT1-2. Previous study showed that sexual reproduction of V. virens plays an important role in the epidemic of RFS. In this study, we developed a loop-mediated isothermal amplification (LAMP) assay to detect the mating type of V. virens easily and rapidly by using specific primers based on the mating type genes MAT1-1-2 and MAT1-2-1, respectively. The LAMP assay used only a water/dry bath and could recognize the mating type of V. virens in just 45 min. The LAMP assay was so sensitive that it could detect small amounts of V. virens genomic DNA (as low as 2.0 pg of MAT1-1 and 200.0 pg of MAT1-2) and was 10 times more sensitive than PCR. In addition, we demonstrated the application of mating type via LAMP assay by assessing the genomic DNA of V. virens isolated from rice fields. The high efficiency and specificity of this LAMP assay suggest that it can be used as a rapid testing tool in mating type recognition of V. virens isolates in the field.
Mapping Blast Resistance Genes in Rice Varieties ‘Minghui 63’ and ‘M-202’
Authors: Jia Yulin , Jia Melissa H. , Yan Zhongbu
Published: November 2021

Rice blast caused by the fungus Magnaporthe oryzae (syn. Magnaporthe grisea) is one of the most lethal diseases for sustainable rice production worldwide. Blast resistance mediated by major resistance genes is often broken down after a short period of deployment, while minor blast resistance genes, each providing a small effect on disease reactions, are more durable. In the present study, we first evaluated disease reactions of two rice breeding parents ‘Minghui 63’ and ‘M-202’ with 11 blast races, IA45, IB1, IB45, IB49, IB54, IC1, IC17, ID1, IE1, IG1, and IH1, commonly present in the United States, under greenhouse conditions using a category disease rating resembling infection types under field conditions. ‘Minghui 63’ exhibited differential resistance responses in comparison with those of ‘M-202’ to the tested blast races. A recombinant inbred line (RIL) population of 275 lines from a cross between ‘Minghui 63’ and ‘M-202’ was also evaluated with the above-mentioned blast races. The population was genotyped with 156 simple sequence repeat (SSR) and insertion and deletion (Indel) markers. A linkage map with a genetic distance of 1,022.84 cM was constructed using inclusive composite interval mapping (ICIM) software. A total of 10 resistance QTLs, eight from ‘Minghui 63’ and two from ‘M-202’, were identified. One major QTL, qBLAST2 on chromosome 2, was identified by seven races/isolates. The remaining nine minor resistance QTLs were mapped on chromosomes 1, 3, 6, 9, 10, 11, and 12. These findings provide useful genetic markers and resources to tag minor blast resistance genes for marker-assisted selection in rice breeding program and for further studies of underlying genes.
Mating-Type Genes Control Sexual Reproduction, Conidial Germination, and Virulence in Cochliobolus lunatus
Authors: Liu K. X. , Jia J. Q. , Chen N. , Fu D. D. , Sun J. Y. , Zhao J. M. , Li J. Y. , Xiao S. Q. , Xue C. S.
Published: November 2021

Cochliobolus lunatus (anamorph: Curvularia lunata) is a major pathogenic fungus that causes the Curvularia leaf spot of maize. ClMAT1-1-1 and ClMAT1-2-1, the C. lunatus orthologs of C. heterostrophus ChMAT1-1-1 and ChMAT1-2-1, were investigated in the present study to uncover their functions in C. lunatus. Southern blot analysis showed that these mating-type MAT genes exist in the C. lunatus genome as a single copy. ClMAT1-1-1 and ClMAT1-2-1 were knocked out and complemented to generate ΔClmat1-1-1 and ΔClmat1-2-1 and ΔClmat1-1-1-C and ΔClmat1-2-1-C, respectively. The mutant strains had defective sexual development and failed to produce pseudothecia. There were no significant differences in growth rate or conidia production between the mutant and wild-type strains. However, the aerial mycelia and mycelial dry weight of ΔClmat1-1-1 and ΔClmat1-2-1 were lower than those of wild type, suggesting that MAT genes affect asexual development. ClMAT genes were involved in the responses to cell wall integrity and osmotic adaptation. ΔClmat1-2-1 had a lower conidial germination rate than the wild-type strain CX-3. The virulence of ΔClmat1-2-1 and ΔClmat1-1-1 was also reduced compared with the wild-type. Complementary strains could restore all the phenotypes.
Toward a CRISPR-Based Point-of-Care Test for Tomato Brown Rugose Fruit Virus Detection
Authors: Bernabé-Orts Joan Miquel , Hernando Yolanda , Aranda Miguel A.
Published: November 2021

Implementing effective monitoring strategies is fundamental to protecting crops from pathogens and ensuring sufficient food supply as the global population continues to grow. This is especially important for emergent plant pathogens such as tomato brown rugose fruit virus (ToBRFV), which overcomes the genetic resistance resources used in tomato breeding against tobamoviruses and has become a pandemic in less than a decade. Here, we report the development of a CRISPR/Cas12a-based test to detect ToBRFV in the laboratory and potentially in a field setting. Using different tobamoviruses to assess specificity, our test showed a clear positive signal for ToBRFV-infected samples, whereas no cross-reactivity was observed for closely related viruses. Next, we compared the limit of detection of our CRISPR-based test with a widely used reference real-time quantitative PCR test, revealing similar sensitivities for both tests. Finally, to reduce complexity and achieve field applicability, we used a fast nucleic acid purification step and compared its results side by side with those of a commonly used column-mediated protocol. The new protocol saved time and resources but at the expense of sensitivity. However, it could still be useful to confirm ToBRFV detection in samples with incipient symptoms of infection. Although there is room for improvement, to our knowledge, this is the first field-compatible CRISPR-based test to detect ToBRFV that combines isothermal amplification with a simplified nucleic acid extraction protocol.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Is it Better to Stop at C2 or C3/4 in Elective Posterior Cervical Decompression and Fusion?
Authors: Roth Steven G. , Khan Inamullah , Chotai Silky , Chanbour Hani , Stephens Byron , Abtahi Amir , Devin Clinton J. , Zuckerman Scott L.
Published: November 2021

Study Design.

Retrospective cohort study.

Objective.

(a) Compare operative variables, complications, and patient-reported outcomes (PROs) in patients with an upper instrumented vertebrae (UIV) of C2 versus C3/4, and (b) assess outcomes based on C2 screw type.

Summary of Background Data.

When performing elective posterior cervical laminectomy and fusion (PCLF), spine surgeons must choose the upper instrumented vertebrae (UIV) at the subaxial cervical spine (C3/4) versus C2. Differences in long-term complications and PROs remain unknown.

Methods.

A single-institution, retrospective cohort study from a prospective registry was conducted. All patients undergoing elective, degenerative PCLF from December 2010 to June 2018 were included. Patients were divided into a UIV of C2 versus C3/4. Groups were 2:1 propensity matched for fusion extending to the thoracic spine. Demographics, operative, perioperative, complications, and 1-year PRO data were collected.

Results.

One hundred seventeen patients underwent elective PCLF and were successfully propensity matched (39 C2 vs. 78 C3/4). Groups were similar in fusion extending to the thoracic spine (P = 0.588). Expectedly, the C2 group had more levels fused (5.63 ± 1.89) compared with the C3/4 group (4.50 ± 0.91) (P = 0.001). The C2 group had significantly longer operative time (P < 0.001), yet no differences were seen in estimated blood loss (EBL) (P = 0.494) or length of stay (LOS) (P = 0.424). Both groups significantly improved all PROs at 1-year (EQ-5D; NRS-NP/AP; NDI). Both groups had the same percentage of surgical adverse events at 6.8% (P = 1.00). Between C2 screw type, no differences were seen in operative time, EBL, LOS, complications, or PROs.

Conclusion.

In patients undergoing elective PCLF, those instrumented to C2 had only longer operative times compared with those stopping at C3/4. No differences were seen in EBL, LOS, 1-year PROs, and complications. Type of C2 screw had no impact on outcomes. Besides increased operative time, instrumenting to C2 had no detectable difference on surgical outcomes or adverse event rates.

Level of Evidence: 3
Multisystem Inflammation and Organ Dysfunction After BNT162b2 Messenger RNA Coronavirus Disease 2019 Vaccination
Authors: Kahn Benjamin , Apostolidis Sokratis A. , Bhatt Vatsal , Greenplate Allison R. , Kallish Staci , LaCava Anthony , Lucas Alfredo , Meyer Nuala J. , Negoianu Dan , Ogdie Alexis R. , Shashaty Michael G. S. , Takach Patricia A. , Zuroff Leah , Wherry E. John , Anesi George L.
Published: November 2021

BACKGROUND:

The U.S. Food and Drug Administration has to date granted approval or emergency use authorization to three vaccines against severe acute respiratory syndrome coronavirus 2 and coronavirus disease 2019. In clinical trials and real-use observational studies, the Pfizer-BioNTech BNT162b2 messenger RNA coronavirus disease 2019 vaccine, as well as the Moderna mRNA-1273 messenger RNA coronavirus disease 2019 vaccine, have demonstrated high efficacy and few adverse events.

CASE SUMMARY:

A 20-year-old male college student in good health developed tinnitus and hematuria shortly after vaccination and progressed swiftly to a syndrome of: systemic inflammation; acute kidney injury requiring hemodialysis; acute, bilateral, complete sensorineural hearing loss; radiographic evidence of acute multifocal ischemic strokes; pericardial effusion complicated by tamponade physiology requiring pericardial evacuation; pleural effusions requiring evacuation; and systemic capillary leak. An extensive clinical and research investigation, including cytokine analysis, whole blood cytometry by time of flight, and whole exome sequencing, did not reveal a definitive explanatory mechanism.

CONCLUSION:

While the overall safety profile of the BNT162b2 coronavirus disease 2019 vaccine remains excellent for the general population, rare serious events have been reported. In this report, we describe a case of multisystem inflammation and organ dysfunction of unknown mechanism beginning shortly after administration of the first dose of BNT162b2 coronavirus disease 2019 vaccine in a previously healthy recipient.
Hypokalemia-Induced Rhabdomyolysis in a Child with Autism Affected by the COVID-19 Pandemic
Authors: Cao Longyue L. , Gaffney Lukas K. , Marcus Carolyn
Published: November 2021

Objective:

Pediatric patients with autism spectrum disorder (ASD) often have coexisting feeding disorders. We hope to emphasize the significant implications that these feeding disorders can have on this patient population through a unique case of hypokalemia-induced rhabdomyolysis.

Method:

We present a unique case of a 3-year-old boy with ASD and a longstanding history of food selectivity whose routine was disrupted during the COVID-19 pandemic resulting in avoidant/restrictive food intake disorder and severe undernutrition, who presented with profound hypokalemia and was subsequently found to have elevated muscle enzymes consistent with rhabdomyolysis despite only subtle complaints of difficulty walking.

Results:

The patient was treated with aggressive hydration, electrolyte therapy, and nasogastric tube feeds, which resulted in clinical and biochemical evidence of improvement. He was also reconnected to ASD-related care services that had lapsed during the COVID-19 pandemic.

Conclusion:

This case exemplifies the adverse impact that feeding disorders can have on patients with ASD, particularly in the setting of stressors such as a global pandemic, and is also the first documented pediatric case of rhabdomyolysis secondary to hypokalemia from severe undernutrition. It demonstrates that physicians should have a low threshold to assess for clinical and laboratory evidence of rhabdomyolysis in patients with profound hypokalemia because symptoms of hypokalemia-induced rhabdomyolysis can often be subtle, which can delay diagnosis and thereby increase the risk for life-threatening complications from extensive muscle damage.
Safety Profile of Endoscopist-directed Balanced Propofol Sedation for Procedural Sedation
Authors: Fatima Hala , Imperiale Thomas
Published: November 2021

Background:

Nurse-administered propofol sedation was restricted to anesthesiologists in 2009, a practice that has contributed to spiraling health care costs in the United States.

Aim:

The aim of this study was to evaluate the safety of endoscopist-directed balanced propofol sedation (EDBPS).

Materials and Methods:

We identified patients undergoing endoscopy with EDBPS from January 1, 2017, to June 20, 2017, and abstracted their medical records. Adverse events (AEs) included: hypoxia (oxygen saturation < 90%); hypotension [(a) systolic blood pressure < 90 mm Hg, (b) systolic blood pressure decline of >50 mm Hg, (c) decline in mean arterial pressure of >30%]; bradycardia (heart rate of < 40 beats/min). Logistic regression identified factors independently associated with AEs.

Results:

A total of 1897 patients received EDBPS during the study period [mean age: 55 y (SD=11.4 y); 56.4% women]. Patients received median doses of 50 µg fentanyl, 2 mg of midazolam, and a mean propofol dose of 160±99 mg. There were no major complications (upper 95% confidence interval, 0.19%). Overall, 334 patients (17.6%) experienced a clinically insignificant AE: 65 (3.4%) experienced transient hypoxia, 277 patients (14.6%) experienced hypotension, 2 had transient bradycardia. In bivariate analysis, older age was associated with risk for hypotension, propofol dose was associated with transient hypoxemia, and procedure duration was associated with both hypotension and transient hypoxia. In multivariate analysis, only procedure length was associated with AEs (odds ratio scale 10; odds ratio=1.07; 95% confidence interval, 1.05-1.09, P<0.001).

Conclusions:

EDBPS is safe for endoscopic sedation. Given the higher cost of anesthesia-administered propofol, endoscopists should reinstate EDBPS by revising institutional sedation policies.