bluuebunny/crossref_metadata_2025 huggingface dataset:
Jugular Foramen Cerebrospinal Fluid Leak Repaired Via the Infralaybryinthine Approach With Adjunct Use of Intrathecal Fluorescein and Stereotactic Navigation
Authors: Patel Tirth R. , Losenegger Tasher , Papagiannopoulos Peter , Jhaveri Miral , Byrne Richard W. , Wiet R. Mark
Published: December 2022

Objective

This report describes a case of a spontaneous cerebrospinal fluid leak at the jugular foramen that was surgically repaired via the infralabyrinthine approach with adjunct use of intrathecal fluorescein and stereotactic navigation.

Patients

A 39-year-old woman presenting with clear otorrhea confirmed to be cerebrospinal fluid (CSF) emanating from a defect in the jugular foramen.

Intervention

Surgical repair of the skull base defect using an infralabyrinthine approach to the jugular foramen. During surgery, intrathecal fluorescein and stereotactic navigation were used to localize the defect and confirm a successful repair.

Main Outcome Measure

Recurrence of a CSF leak.

Results

The defect was successfully repaired using the techniques described, resulting in cessation of the patient's CSF leak. There was no recurrence of the CSF leak up to a 4-month postoperative outpatient follow-up.

Conclusions

Diagnosis and repair of spontaneous otogenic CSF leaks in an uncommon location like the jugular foramen are challenging. This report demonstrates the successful use of the infralabyrinthine approach for control of a CSF from the jugular foramen. In addition, use of techniques, such as intrathecal fluorescein and stereotactic navigation that are not routinely used in otology and neurotology allowed for safe, effective repair of the leak in this case.
Endolymphatic Hydrops in the Setting of Vestibular Schwannoma: A Temporal Bone Study
Authors: Wong Yu-Tung , Lopez Ivan A. , Wichova Helena , Ishiyama Akira , Miller Mia E.
Published: December 2022

Hypothesis

Vestibular schwannoma (VS) may be associated with endolymphatic hydrops (EH). EH may account for symptomatology in a subset of patients with VS.

Background

Presenting symptoms of VS and EH overlap, and MRI evaluation of the membranous labyrinth in some patients with VS demonstrates EH. The aim of the current study is to evaluate whether EH is present in temporal bones of patients with VS.

Methods

The NIDCD and House Temporal Bone Laboratory at UCLA Eccles database was queried for the diagnosis of “acoustic neuroma.” Exclusion criteria included concomitant ear disease and surgery. Temporal bones were analyzed for EH of the basal, middle, and apical turns and vestibule. Premortem audiometric and clinical data were gathered.

Results

Of 43 human temporal bones with VS, 6 met inclusion criteria. All temporal bones demonstrated VS that was undisturbed by surgery. Three of six demonstrated EH of at least one cochlear turn as well as vestibular hydrops. Three patients had severe to profound hearing loss. One patient carried a diagnosis of Menière’s disease.

Conclusions

EH is demonstrated in the setting of VS in human temporal bones. EH may be one mechanism of hearing loss and dizziness in patients with VS.

Professional Practice Gap and Educational Need

The underlying mechanisms of symptoms of VS may be multifactorial. The association of EH in some patients with VS would modify our clinical approach to management.

Learning Objective

To discover if EH may be associated with VS.

Desired Result

To broaden understanding of pathophysiologic mechanisms in patients with VS.

Level of Evidence

Level IV

IRB Approved: UCLA IRB No. 10-001449
Adding Kinetic Energy Does Not Further Improve Treatment Outcomes With a Mechanical Reposition Chair: A Randomized Controlled Trial
Authors: Kjærsgaard Jonas Bruun , Petersen Niels Krintel , Hougaard Dan Dupont
Published: December 2022

Objective

To test if the addition of abrupt deaccelerations (kinetic energy) during treatment with a mechanical repositional chair (MRC) provides improved treatment efficacy with treatment of posterior benign paroxysmal positional vertigo (BPPV).

Study Design

Randomized two-armed parallel open-labeled clinical trial.

Setting

Tertiary referral center.

Patients

Seventy patients diagnosed with posterior canalolithiasis BPPV were included.

Intervention(s)

All patients underwent diagnostics and treatment with an MRC. Patients were randomized to either a traditional Epley maneuver or a potentiated version of the Epley maneuver where kinetic energy was applied in five positions with 45-degree turns between each step.

Main Outcome Measure(s)

Primary endpoint was the number of treatments needed before complete resolution of both subjective symptoms and objective signs of BPPV within the semicircular canal of interest. Secondary endpoints included the following: 1) number of patients requiring more than 10 treatments, 2) length of treatment in days before treatment(s) were successful, and 3) changes in total Dizziness Handicap Inventory scores before and after treatment.

Results

No significant difference in the number of required treatments between the two treatment arms was found. Approximately three of four subjects were cured after two repositional maneuvers regardless of type of treatment. An equal length of treatment was seen with both groups, and the Dizziness Handicap Inventory scores were significantly lowered after treatment with no significant differences between the two types of treatment.

Conclusions

Both the traditional and the potentiated Epley maneuver are efficient in treatment of canalolithiasis of the posterior semicircular canals with MRC. Addition of kinetic energy with this subgroup of BPPV patients does not seem to add further efficacy to the treatment.
68Ga–Prostate-Specific Membrane Antigen PET/CT in Ovarian Tumors
Authors: Kunikowska Jolanta , Bizoń Magdalena , Pełka Kacper , Derlatka Paweł , Olszewski Maciej , Królicki Leszek
Published: December 2022

Purpose of the Report

Ovarian cancer is usually diagnosed in an advanced stage of disease due to the absence of specific symptoms and a lack of sensitive diagnostic methods. Prostate-specific membrane antigen (PSMA) is expressed on prostate cancer cells but can be found in other tumors such as ovarian cancer.

The aim of this pilot study was to evaluate the feasibility of using 68Ga-PSMA-11 PET/CT in detection of ovarian neoplasm before surgical treatment.

Patients and Methods

Eight women with mean age of 56.0 ± 16.2 years were included in the study. All patients underwent transvaginal ultrasound followed by CT scan of the chest and abdomen as qualification for surgery. Within a 1-week interval, PET/CT was performed on a Siemens Biograph scanner, 60 minutes after injection of 2 MBq/kg 68Ga-PSMA-11.

Results

In 3 cases (37.5%), the 68Ga-PSMA-11 PET/CT was positive, whereas histological examination confirmed 2 serous ovarian cancer cases and 1 ovarian borderline tumor. The SUVmax in the serous ovarian cancer was 8.7 and 4.1, and in the borderline ovarian tumor, it was 13.8. No correlation was found between antigen CA-125 level and 68Ga-PSMA expression. Range of tumor SUVmax was not correlated with stage of disease. The remaining 62.5% (5/8) were negative in 68Ga-PSMA-11 PET/CT, and histopathology confirmed benign pelvic tumor.

Conclusions

The initial experience supports the potential to use 68Ga-PSMA-11 in ovarian cancer to differentiate malignant and benign tumors before surgery.

This study was approved by the Ethical Committee of the Medical University of Warsaw (KB/2/A/2018).
Identification of and discrimination between the Mycobacterium abscessus complex and Mycobacterium avium complex directly from sputum using quadruplex real-time PCR
Authors: Dziedzinska Radka , Okunkova Jana , Kralik Petr , Svobodova Jana , Mala Miriam , Slana Iva
Published: December 2022

Introduction. Cystic fibrosis (CF) is a serious disease with multisystemic clinical signs that is easily and frequently complicated by bacterial infection. Recently, the prevalence of nontuberculous mycobacteria as secondary contaminants of CF has increased, with the

Mycobacterium avium

complex (MAC) and

Mycobacterium abscessus

complex (MABSC) being the most frequently identified. The MABSC includes subspecies of significant clinical importance, mainly due to their resistance to antibiotics.

Gap statement. Sensitive method for early detection and differentiation of MABSC members and MAC complex for use in routine clinical laboratories is lacking. A method based on direct DNA isolation from sputum, using standard equipment in clinical laboratories and allowing uncovering of possible sample inhibition (false negative results) would be required. The availability of such a method would allow accurate and accelerated time detection of MABSC members and their timely and targeted treatment.

Aim. To develop a real time multiplex assay for rapid and sensitive identification and discrimination of MABSC members and MAC complex.

Methodology. The method of DNA isolation directly from the sputum of patients followed by quadruplex real-time quantitative PCR (qPCR) detection was developed and optimised. The sensitivity and limit of detection (LOD) of the qPCR was determined using human sputum samples artificially spiked with a known amount of

M. abscessus

subsp.

massiliense

(MAM).

Results. The method can distinguish between MAC and MABSC members and, at the same time, to differentiate between

M. abscessus

subsp.

abscessus

/subsp. bolletii (MAAb/MAB) and MAM. The system was verified using 61 culture isolates and sputum samples from CF and non-CF patients showing 29.5 % MAAb/MAB, 14.7 % MAM and 26.2 % MAC. The LOD was determined to be 1 490 MAM cells in the sputum sample with the efficiency of DNA isolation being 95.4 %. Verification of the qPCR results with sequencing showed 100 % homology.

Conclusions. The developed quadruplex qPCR assay, which is preceded by DNA extraction directly from patients’ sputum without the need for culturing, significantly improves and speeds up the entire process of diagnosing CF patients and is therefore particularly suitable for use in routine laboratories.
Low-intensity transcranial focused ultrasound suppresses pain by modulating pain processing brain circuits
Authors: Kim Min Gon , Yu Kai , Yeh Chih-Yu , Fouda Raghda , Argueta Donovan , Kiven Stacy , Ni Yunruo , Niu Xiaodan , Chen Qiyang , Kim Kang , Gupta Kalpna , He Bin
Published: December 2022

There is an urgent and unmet clinical need to develop non-pharmacological interventions for chronic pain management due to the critical side effects of opioids. Low-intensity transcranial focused ultrasound is an emerging non-invasive neuromodulation technology with high spatial specificity and deep brain penetration. Here, we developed a tightly-focused 128-element ultrasound transducer to specifically target small mouse brains, employing dynamic focus steering. We demonstrate that transcranial focused ultrasound stimulation at pain processing brain circuits can significantly alter pain-associated behaviors in mouse models in vivo. Our findings indicate that a single-session focused ultrasound stimulation to the primary somatosensory cortex (S1) significantly attenuates heat pain sensitivity in wild-type mice and modulates heat and mechanical hyperalgesia in a humanized mouse model of chronic pain in sickle cell disease. Results further revealed a sustained behavioral change associated with heat hypersensitivity by targeting deeper cortical structures (e.g., insula) and multi-session focused ultrasound stimulation to S1 and insula. Analyses of brain electrical rhythms through electroencephalography demonstrated a significant change in noxious heat hypersensitive- and chronic hyperalgesia-associated neural signals following focused ultrasound treatment. Validation of efficacy was carried out through control experiments, tuning ultrasound parameters, adjusting inter-experiment intervals, and investigating effects on age, gender, genotype, and in a head-fixed awake model. Importantly, transcranial focused ultrasound was shown to be safe, causing no adverse effects on motor function and brain neuropathology. In conclusion, the rich experimental evidence validates the ability of novel focused ultrasound neuromodulation to suppress pain, presenting significant translational potential for next-generation chronic pain treatment without adverse effects.

Key points

Novel non-invasive neuromodulation of brain’s pain processing circuits with submillimeter spatial precision for pain management

Transcranial focused ultrasound significantly modulates pain-related behaviors and brain electrical rhythms of pain in humanized SCD mice
COVID-19 Reinfections in Mexico City: Implications for public health response
Authors: de Anda-Jauregui Guillermo , Gómez-Romero Laura , Cedro-Tanda Alberto , Cañas Sofía , Campos-Romero Abraham , Alcantar-Fernández Jonathan , Hidalgo-Miranda Alfredo , Herrera Luis A.
Published: December 2022

Background

SARS-CoV-2 pandemia continues to be important even when more than 60% of the global population has been vaccinated. As the pandemia evolves the number of reinfection cases will continue to increase as new variants are generated that evade the immune response. Understanding reinfections is important to guide the public health system and to inform decision-makers.

Methods

We downloaded clinical outcome and severity of infection data from the SISVER (respiratory disease epidemiological surveillance system) database. We sequenced SARS-CoV-2 samples, identified SARS-CoV-2 lineage and upload this genomic data to GISAID. We analyzed time and lineage between index infection and reinfection. We also analyzed the clinical outcome, severity of infection and vaccination status during reinfections.

Findings

In this study we confirmed that each wave of SARS-CoV-2 infections was characterized by a different viral variant showing a prevalence higher that 95%. We found that the fraction of reinfection is not linearly related to the average time of separation between waves with 40% of all the reinfections occurring at wave 5, the only wave with more than one SARS-CoV-2 variant with a prevalence higher than 80%. Regarding type of care 2.63% patients were considered ambulatory during the reinfection even when they were hospitalized during the index infection and only 0.78% presented the opposite behavior. Moreover, 6.74% reinfections transitioned from asymptomatic to mild or severe or from mild to severe; and 8.95% transitioned from severe to mild or asymptomatic or from mild to asymptomatic. The highest number of reinfections have occurred in unvaccinated patients (41.6%), followed shortly by vaccinated patients (31.9%). However, most reinfections occurred after wave 4 when the national vaccination efforts have reached 65% of the general population.

Interpretation

The analyzed data suggests a diminished severity of infection during reinfection either if transitions in disease severity or transitions in type of patient care are considered. Finally, we also observed an overrepresentation of unvaccinated patients in reinfections.
Cryo-EM map anisotropy can be attenuated by map post-processing and a new method for its estimation
Authors: Sanchez-Garcia Ruben , Gaullier Guillaume , Cuadra-Troncoso Jose Manuel , Vargas Javier
Published: December 2022

One of the most important challenges in cryogenic electron microscopy (cryo-EM) is the substantial number of samples that exhibit preferred orientations, which leads to an uneven coverage of the projection sphere. As a result, the overall quality of the reconstructed maps can be severely affected, as manifested by the presence of anisotropy in the map resolution. Several methods have been proposed to measure the directional resolution of maps in tandem with experimental protocols to address the problem of preferential orientations in cryo-EM. Following these works, in this manuscript we identified one potential limitation that may affect most of the existing methods and we proposed an alternative approach to evaluate the presence of preferential orientations in cryo-EM reconstructions. In addition, we also showed that some of the most recently proposed cryo-EM map post-processing algorithms can attenuate map anisotropy, thus offering alternative visualization opportunities for cases affected by moderate levels of preferential orientations.
Explaining the primate extinction crisis: predictors of extinction risk and active threats
Authors: Creighton Maria J.A. , Nunn Charles L.
Published: December 2022

Explaining why some species are disproportionately impacted by the extinction crisis is of critical importance for conservation biology as a science and for proactively protecting species that are likely to become threatened in the future. Using the most current data on threat status, population trends, and threat types for 446 primate species, we advance previous research on the determinants of extinction risk by including a wider array of phenotypic traits as predictors, filling gaps in these trait data using multiple imputation, and investigating the mechanisms that connect organismal traits to extinction risk. Our Bayesian phylogenetically controlled analyses reveal that insular species exhibit higher threat status, while those that are more omnivorous and live in larger groups have lower threat status. The same traits are not linked to risk when repeating our analyses with older IUCN data, which may suggest that the traits influencing species risk are changing as anthropogenic effects continue to transform natural landscapes. We also show that non-insular, larger-bodied, and arboreal species are more susceptible to key threats responsible for primate population declines. Collectively, these results provide new insights to the determinants of primate extinction and identify the mechanisms (i.e., threats) that link traits to extinction risk.
Highly dynamic evolution of the chemosensory system driven by gene gain and loss across subterranean beetles
Authors: Balart-García Pau , Bradford Tessa M. , Beasley-Hall Perry G. , Polak Slavko , Cooper Steven J. B. , Fernández Rosa
Published: December 2022

Chemical cues in subterranean habitats differ highly from those on the surface due to the contrasting environmental conditions, such as absolute darkness, high humidity or food scarcity. Subterranean animals underwent changes to their sensory systems to facilitate the perception of essential stimuli for underground lifestyles. Despite representing unique systems to understand biological adaptation, the genomic basis of chemosensation across cave-dwelling species remains unexplored from a macroevolutionary perspective. Here, we explore the evolution of chemoreception in three beetle tribes that underwent at least six independent transitions to the underground, through a phylogenomics spyglass. Our findings suggest that the chemosensory gene repertoire varies dramatically between species. Overall, no parallel changes in the net rate of evolution of chemosensory gene families were detected prior, during, or after the habitat shift among subterranean lineages. Contrarily, we found evidence of lineage-specific changes within surface and subterranean lineages. However, our results reveal key duplications and losses shared between some of the lineages transitioning to the underground, including the loss of sugar receptors and gene duplications of the highly conserved ionotropic receptors IR25a and IR8a, involved in thermal and humidity sensing among other olfactory roles in insects. These duplications were detected both in independent subterranean lineages and their surface relatives, suggesting parallel evolution of these genes across lineages giving rise to cave-dwelling species. Overall, our results shed light on the genomic basis of chemoreception in subterranean beetles and contribute to our understanding of the genomic underpinnings of adaptation to the subterranean lifestyle at a macroevolutionary scale.
Trait-specific indirect effects underlie variation in the response of spiders to cannibalistic social partners
Authors: Henriques Jorge F. , Lacava Mariángeles , Guzman Celeste , Gavin-Centol Maria Pilar , Ruiz-Lupión Dolores , Ruiz Alberto , Viera Carmen , Moya-Laraño Jordi , Magalhães Sara
Published: December 2022

Organisms may respond in different ways to the risk posed by conspecifics, but the cause of such variation remains elusive. Here, we use a half-sib/full-sib design to evaluate the contribution of (indirect) genetic or environmental effects to the behavioral response of the cannibalistic wolf spiderLycosa fasciiventris(Dufour, 1835) towards conspecific cues. Spiders showed variation in relative occupancy time, activity, and velocity on patches with or without conspecific cues, but direct genetic variance was only found for occupancy time. These three traits were correlated and could be lumped in a principal component: spiders spending more time in patches with conspecific cues moved less and at a lower rate in those areas. Genetic and/or environmental components of carapace width and weight loss in the social partner were significantly correlated with the principal component of focal individuals. Variation in these traits may reflect the quality and/or quantity of cues produced by social partners, hence focal individuals were likely behaving along a continuum of strategies in response to the risk posed by social partners. Therefore, environmental and genetic trait variation in the social partners may be key to maintain trait diversity in focal individuals, even in the absence of direct genetic variation.
The more synthetic polymer types pollute the soil, the stronger the growth suppression of invasive alien and native plants
Authors: Fu Yanmei , van Kleunen Mark , Ma Kai , Liu Yanjie
Published: December 2022

Although most studies on the ecological effects of microplastic pollution focus on a single type of synthetic polymer and a single species, most organisms will be exposed to multiple polymer types simultaneously and the effects may vary among species. To test the effects of polymer diversity on plants, we grew single plants of eight invasive and eight native species in pots with substrate polluted by 0, 1, 3 and 6 types of micro-sized synthetic polymers. We found that the growth suppression by microplastic pollution became stronger with the number of polymer types the plants were exposed to. This tended to be particularly the case for invasive species, whose biomass advantage over natives diminished with the number of polymer types. Our study thus shows that the negative effects of microplastic pollution on plant growth increase with the number of polymer types, and that these effects differ between invasive and native species.
Towards a Clinically-based Common Coordinate Framework for the Human Gut Cell Atlas - The Gut Models
Authors: Burger Albert , Baldock Richard , Adams David J , Din Shahida , Papatheodorou Irene , Glinka Michael , Hill Bill , Houghton Derek , Sharghi Mehran , Wicks Michael , Arends Mark J
Published: December 2022

Background

The Human Cell Atlas resource will deliver single cell transcriptome data spatially organised in terms of gross anatomy, tissue location and with images of cellular histology. This will enable the application of bioinformatics analysis, machine learning and data mining revealing an atlas of cell types, sub-types, varying states and ultimately cellular changes related to disease conditions. To further develop the understanding of specific pathological and histopathological phenotypes with their spatial relationships and dependencies, a more sophisticated spatial descriptive framework is required to enable integration and analysis in spatial terms.

Methods

We describe a conceptual coordinate model for the Gut Cell Atlas (small and large intestines). Here, we focus on a Gut Linear Model (1-dimensional representation based on the centreline of the gut) that represents the location semantics as typically used by clinicians and pathologists when describing location in the gut. This knowledge representation is based on a set of standardised gut anatomy ontology terms describing regionsin situ, such as ileum or transverse colon, and landmarks, such as ileo-caecal valve or hepatic flexure, together with relative or absolute distance measures. We show how locations in the 1D model can be mapped to and from points and regions in both a 2D model and 3D models, such as a patient’s CT scan where the gut has been segmented.

Results

The outputs of this work include 1D, 2D and 3D models of the human gut, delivered through publicly accessible Json and image files. We also illustrate the mappings between models using a demonstrator tool that allows the user to explore the anatomical space of the gut. All data and software is fully open-source and available online.

Conclusions

Small and large intestines have a natural “gut coordinate” system best represented as a 1D centreline through the gut tube, reflecting functional differences. Such a 1D centreline model with landmarks, visualised using viewer software allows interoperable translation to both a 2D anatomogram model and multiple 3D models of the intestines. This permits users to accurately locate samples for data comparison.
md_harmonize: a Python package for atom-level harmonization of public metabolic databases
Authors: Jin Huan , Moseley Hunter N.B.
Published: December 2022

A big challenge to integrating public metabolic resources is the use of different nomenclatures by individual databases. This paper presents md_harmonize, an open-source Python package for harmonizing compounds and metabolic reactions across various metabolic databases. md_harmonize utilizes a neighborhood-specific graph coloring method for generating a unique identifier for each compound via atom identifiers based on the compound structure. The resulting harmonized compounds and reactions can be used to construct metabolic networks and models for various downstream analyses, including metabolic flux analysis.

Availability

The md_harmonize package is implemented in Python and freely available athttps://github.com/MoseleyBioinformaticsLab/md_harmonize

Contact

hunter.moseley@uky.edu

Supplementary information

Supplementary data are available athttps://doi.org/10.6084/m9.figshare.21699683.
The effect of vaccination on transmission of SARS-CoV-2 (COVID-19): a rapid review
Authors: Williams Jessica , Barratte Sasha , Winfield Tom , Elston Lauren , McDermott Katie , Jarrom David , Hasler Elise , Potter Caron , Lewis Ruth , Cooper Alison , Edwards Adrian
Published: December 2022

This is an update (literature search up to 15 March 2022) of arapid reviewexamining whether vaccination against SARS-CoV-2 (COVID-19) affects transmission of SARS-CoV-2.

Streamlined systematic methodologies were used to accelerate the review process.

The update identified 17 additional studies: 6 studies reported on transmission and 11 studies reported viral load. There was high heterogeneity across studies, which varied in design, participant characteristics and SARS-CoV-2 variants reported. Evidence from this update supports previous findings that that transmission of Omicron and Delta variants is lowest in booster-vaccinated people, followed by fully vaccinated people, with the highest rate of transmission in unvaccinated people. Additionally, some studies compared transmission between different variants or sub-variants; risk of transmission appears to be higher with Omicron than Delta, regardless of vaccination status.

Funding statement

Health Technology Wales was funded for this work by the Wales COVID-19 Evidence Centre, itself funded by Health and Care Research Wales on behalf of Welsh Government.
Cuticle supplementation and nitrogen recycling by a dual bacterial symbiosis in a family of xylophagous beetles (Coleoptera: Bostrichidae)
Authors: Kiefer Julian Simon Thilo , Bauer Eugen , Okude Genta , Fukatsu Takema , Kaltenpoth Martin , Engl Tobias
Published: December 2022

Many insects engage in stable nutritional symbioses with bacteria that supplement limiting essential nutrients to their host. While several plant sap-feeding Hemipteran lineages are known to be simultaneously associated with two or more endosymbionts with complementary biosynthetic pathways to synthesize amino acids or vitamins, such co-obligate symbioses have not been functionally characterized in other insect orders. Here, we report on the characterization of a dual co-obligate, bacteriome-localized symbiosis in a family of xylophagous beetles using comparative genomics, fluorescence microscopy, and phylogenetic analyses. Across the beetle family Bostrichidae, all investigated species harbored the Bacteroidota symbiontShikimatogenerans bostrichidophilusthat encodes the shikimate pathway to produce tyrosine precursors in its severely reduced genome, likely supplementing the beetles’ cuticle biosynthesis, sclerotisation, and melanisation. One clade of Bostrichid beetles additionally housed the co-obligate symbiontBostrichicola ureolyticusthat is inferred to complement the function ofShikimatogeneransby recycling urea and provisioning the essential amino acid lysine, thereby providing additional benefits on nitrogen-poor diets. Both symbionts represent ancient associations within the Bostrichidae that have subsequently experienced genome erosion and co-speciation with their hosts. WhileBostrichicolawas repeatedly lost,Shikimatogeneranshas been retained throughout the family and exhibits a perfect pattern of co-speciation. Our results reveal that co-obligate symbioses with complementary metabolic capabilities occur beyond the well-known sap-feeding Hemiptera and highlight the importance of symbiont-mediated cuticle supplementation and nitrogen recycling for herbivorous beetles.

Significance statement

Nutritional symbioses evolved frequently in insects and contribute diverse metabolites to their hosts’ physiology. Associations with dual symbionts providing complementary nutrients evolved in multiple Hemiptera lineages, compensating eroded biosynthetic capabilities of primary symbionts. Bostrichidae, a family of xylophagous beetles, harbor consistently a Flavobacterial symbiont encoding exclusively the Shikimate pathway to synthesis precursors of tyrosine. However, in two families a second, closely Flavobacterial symbiont capable of recycling urea and synthesizing lysine was retained. Both symbionts exhibit high genomic syntheny and tight co-cladogenesis with the host phylogeny, indicating ancestral, ecological highly beneficial symbioses.
The Arabidopsis Target of Rapamycin (TOR) kinase regulates ammonium assimilation and glutamine metabolism
Authors: Ingargiola Camille , Jéhanno Isabelle , Forzani Céline , Marmagne Anne , Broutin Justine , Clément Gilles , Leprince Anne-Sophie , Meyer Christian
Published: December 2022

In Eukaryotes, Target of Rapamycin (TOR) is a well conserved kinase that controls cell metabolism and growth in response to nutrients and environmental factors. Nitrogen (N) is an essential element for plants and TOR functions as a crucial N and amino acid sensor in animals and yeast. However, the knowledge on the connections between TOR and the overall N metabolism and assimilation in plants is still limited. In this study, we investigate the regulation of TOR in Arabidopsis by the N source as well as the impact of TOR deficiency on N metabolism. Inhibition of TOR globally decreases ammonium uptake while triggering a massive accumulation of amino acids such as Gln, but also of polyamines. Coherently, TOR complex mutants were found to be hypersensitive to Gln. We also show that the glutamine synthetase inhibitor glufosinate abolishes Gln accumulation resulting from TOR inhibition and improves the growth of TOR complex mutants. These results suggest that a high level of Gln contributes to the reduction in plant growth resulting from TOR inhibition. Glutamine synthetase activity was reduced by TOR inhibition while the enzyme amount increased. In conclusion our findings show that the TOR pathway is intimately connected to N metabolism and that a decrease in TOR activity results in a glutamine synthetase-dependent Gln and amino acids accumulation.

One sentence summary

The conserved Target of Rapamycin (TOR) kinase is an important sensor and regulator of the nitrogen metabolism and here we show that inhibiting this kinase affects ammonium uptake and results in Gln accumulation in a glutamine synthetase-dependent manner.
Cuticle development and underlying transcriptome-metabolome associations during early seedling establishment
Authors: Chen Keting , Bhunia Rupam Kumar , McNinch Colton , Campidilli Grace , Hassan Ahmed , Li Ling , Nikolau Basil J. , Yandeau-Nelson Marna D.
Published: December 2022

The plant cuticle is a complex extracellular lipid barrier that provides protection from numerous environmental stressors and is critical for normal organ development. In this study, we investigated cuticle deposition by integrating metabolomics and transcriptomics data gathered from six different maize seedling organs of four genotypes, the inbred lines B73 and Mo17, and their reciprocal hybrids. These datasets captured the developmental transition of the seedling from heterotrophic skotomorphogenic growth to autotrophic photomorphogenic growth, which is a transition that is highly vulnerable to environmental stresses. Statistical interrogation of these data reveals that the predominant determinant of cuticle composition is seedling organ type, whereas the seedling genotype has a smaller effect on this phenotype. Gene-to-metabolite associations assessed by joint statistical analyses of transcriptome and metabolome datasets identified three gene networks connected with the deposition of different fractions of the cuticle: a) cuticular waxes; b) cutin of aerial organs and suberin of roots; and c) both of these fractions. These networks consist of genes that encode known components of the machinery that supports cuticle deposition, demonstrating the utility of this integrated omics approach. Moreover, these gene networks reveal three additional metabolic programs that appear to support cuticle deposition, including processes of a) chloroplast biogenesis, b) lipid metabolism, and c) molecular regulation (e.g., transcription factors, post-translational regulators and phytohormones). This study demonstrates the wider physiological metabolic context that can determine cuticle deposition and lays the groundwork for new targets for modulating properties of this protective barrier.
The Use and Safety Risk of Repurposed Drugs for COVID-19 patients: Lessons Learned Utilizing the Food and Drug Administration’s Adverse Event Reporting System
Authors: Alsuhaibani Deemah S. , Edrees Heba H. , Alshammari Thamir M
Published: December 2022

Objectives

This study was designed to assess the disproportionality analyses of adverse drug reactions (ADRs) related to hydroxychloroquine and remdesivir and how ADR reporting fluctuated during the COVID-19 pandemic.

Methods

A retrospective observational study was conducted utilizing the Food and Drug Administration’s Adverse Event Reporting System (FAERS) data between 2019 and 2021. The study was conducted in two phases. In the first phase, all reports associated with the drugs of interest were evaluated to assess all related adverse drug reactions. In the second phase, specific outcomes of interest (i.e., QT prolongation and renal and hepatic events) were determined to study their association with the drugs of interest. A descriptive analysis was conducted for all adverse reactions related to the drugs being studied. In addition, disproportionality analyses were conducted to compute the reporting odds ratio, the proportional reporting ratio, the information component, and the empirical Bayes geometric mean. All analyses were conducted using RStudio.

Results

A total of 9,443 ADR reports related to hydroxychloroquine; 6,160 (71.49) patients were female, and higher percentage of patients of both sexes were over the age of 65 years. QT prolongation (1.48%), pain (1.38%), and arthralgia (1.25%) were most frequently reported ADRs during the COVID-19 pandemic. The association of QT prolongation with use of hydroxychloroquine was statistically significant (ROR 47.28 [95% CI 35.95-62.18]; PRR 42.41 [95% CI 32.25-55.78]; EBGM 16.08; IC 4.95) compared with fluoroquinolone. The outcome was serious medical events in 48.01% of ADR reports; 27.42% required hospitalization and 8.61% resulted in death. Of 6,673 ADR reports related to remdesivir, 3,928 (61.13%) patients were male. During 2020, the top three ADR reports were elevated liver function tests (17.26%), acute kidney injury (5.95%) and death (2.84%). Additionally, 42.71% of ADR reports indicated serious medical events; 19.69% resulted in death and 11.71% indicated hospitalization. The ROR and PRR of hepatic and renal events associated with remdesivir were statistically significant, (4.81 [95% CI 4.46-5.19] and 2.96 [95% CI 2.66-3.29], respectively.

Conclusion

Our study showed that several serious ADRs were reported with the use of hydroxychloroquine, which resulted in hospitalization and death. Trends with the use of remdesivir were similar, but to a lesser extent. Therefore, this study showed us that off-label use should be based on thorough evidence-based evaluation.
Identification of Barley Enhancers across Genome via STARR-seq
Authors: Zhou Wanlin , Shi Haoran , Wang Zhiqiang , Huang Yuxin , Ni Lin , Chen Xudong , Liu Yan , Li Haojie , Li Caixia , Liu Yaxi
Published: December 2022

Enhancers are DNA sequences that can strengthen transcription initiation. However, the global identification of plant enhancers is complicated due to uncertainty in the distance and orientation of enhancers, especially in species with large genomes. In this study, we performed self-transcribing active regulatory region sequencing (STARR-seq) for the first time to identify enhancers across the barley genome. A total of 7323 enhancers were successfully identified, and among 45 randomly selected enhancers, over 75% were effective as validated by a dual-luciferase reporter assay system in the lower epidermis of tobacco leaves. Interestingly, up to 53.5% of the barley enhancers were repetitive sequences, especially transposable elements (TEs), thus reinforcing the vital role of repetitive enhancers in gene expression. Both the common active transcription marker H3K4me3 and repressive histone marker H3K27me3 were abundant among the barley STARR-seq enhancers. In addition, the functional range of barley STARR-seq enhancers seemed much broader than that of rice or maize and extended to ± 100 KB of the gene body, and this finding was consistent with the high expression levels of genes in the genome. This work specifically depicts the unique features of barley enhancers and provides available barley enhancers for further utilization.
Different neuroendocrine cell types in thepars intercerebralisofPeriplaneta americanaproduce their own specific IGF-related peptides
Authors: Veenstra Jan A.
Published: December 2022

Of the nine genes of the American cockroach,Periplaneta americana, coding for peptides related to insulin and insulin-like growth factor, seven show significant expression in the central nervous system as demonstrated by the polymerase chain reaction on reverse transcribed RNA.In situhybridisation shows that five of those are expressed by cells in thepars intercerebralis. Antisera raised to the predicted peptides show that these cells are neuroendocrine in nature and project to thecorpora cardiaca. Interestingly, there are at least three cell types that each express different genes. This contrasts withDrosophilawhere a single cell type expresses a number of genes expressing several such peptides. Whereas inDrosophilathe neuroendocrine cells producing insulin-like peptides also express sulfakinins, the arthropod orthologs of gastrin and cholecystokinin, inPeriplanetathe sulfakinins are produced by different cells. Other neuropeptides known to be produced by thepars intercerebralisinPeriplanetaand other insect species, such as the CRF-like diuretic hormone, neuroparsin, leucokinin or myosuppressin, neither colocalize with an insulin-related peptide. The separate cellular localization of these peptides and the existence of multiple insulin receptors in this species implies a more complex regulation by insulin and IGF-related peptides in cockroaches than in the fruit fly.
Use of an ultrasound picture archiving and communication system (PACS) to answer research questions: description of data cleaning methods
Authors: Moore Matthew K , Whalley Gillian , Jones Gregory T , Coffey Sean
Published: December 2022

Background

Ultrasound picture archiving and communication system (PACS) databases are useful for quality improvement and clinical research, but frequently contain free text that is not easily readable. Here, we present a method to extract and clean a semi-structured echocardiography (cardiac ultrasound) PACS database.

Methods

Echocardiography studies between 1 January 2010 and 31 December 2018 were extracted using a data mining tool. Numeric variables were recoded with extreme values excluded. Analysis of free text, including descriptions of the heart valves and right and left ventricular size and function, was performed using a rule-based system. Different levels of free text variables were initially identified using commonly used phrases, and then iteratively developed. Randomly selected sets of 100 studies were compared to the electronic health record to validate the data cleaning process.

Results

The data validation step was performed three times in total, with the Cohen’s kappa ranging between 0.88 and 1.00 for the final set of data validation across all measures.

Conclusion

Free text cleaning of semi-structured PACS databases is possible using freely available open source software. The accuracy of this method is high, and the resulting dataset can be linked to administrative data to answer research questions. We present a method that could be used to answer clinical questions or to develop quality improvement initiatives.
Horizontal transmission of penicillin binding protein 1A caused a nationwide spread of β-lactam resistance in pneumococci
Authors: Nakano Satoshi , Fujisawa Takao , Chang Bin , Ito Yutaka , Kitamura Norikazu , Suga Shigeru , Matsumura Yasufumi , Yamamoto Masaki , Nagao Miki , Ohnishi Makoto , Sugai Motoyuki
Published: December 2022

The emergence and spread of drug-resistant bacteria continue to be a global crisis. The mechanism of the resistance spread via mobile genetic elements such as plasmids is well known, however, the impact of the natural transformation on the spread remains unclear.Streptococcus pneumoniaeis well known to be a transformable pathogen by natural competence and they become β-lactam resistance by the acquisition of chromosomal genetic elements including mutated PBPs by natural transformation. To trace the transmission of pneumococcal PBPs among nationwide pediatric population and analyze the impact of transformed PBPs to β-lactam resistance, we collected and analyzed more than 1300 isolates ofS. pneumoniaethrough nationwide surveillance study for pediatric pneumococcal diseases between 2012-2017 in Japan.

We discovered a high prevalence of a specific PBP1A type (pbp1a-13) in β-lactam resistant pneumococci that had a 370SSMK substitution in their β-lactam binding SXXK motif, suggesting that thispbp1a-13 transferred horizontally between different clones resulting in emergence and spread of β-lactam resistant pneumococcal clones. Divergence dating analysis suggested thatpbp1a-13 was inserted into major resistant lineages in the early 1990s through the 2000s, before introduction of pneumococcal conjugate vaccines in Japan. Our additional analysis for pneumococcal isolates that were recovered in the 90s in Japan suggested thatpbp1a-13 in GPSC1 (serotype 19F-CC236) and GPSC14 (serotype 23F-CC242) isolates were the origin of the currently spreadpbp1a-13. We provide evidence ofpbp1ahorizontal transmission at a nationwide scale and highlight the importance of PBP profile monitoring for identifying the emergence and spread of resistant pneumococci lineages.
Isolation of highly purified genomic material from mitochondria of muscle tissue cells
Authors: Tatarkina M.A. , Lobanova V.V. , I.I. Kozenkov I.I. , Efimenko B.E. , Dzhigkaev A. K. , Popadin K.Y. , Gunbin K.V. , Goncharov A.G.
Published: December 2022

In this work, we adapted a method for isolation of a highly purified fraction of mitochondrial DNA from muscle tissues suitable for further sample preparation of libraries without an amplification step for sequencing tasks on various NGS platforms and a method for evaluating the purity of DNA from contamination by nuclear genome regions.

We optimized several techniques7,8for enrichment of the mitochondrial fractions and purifying mtDNA. Here, we describe a protocol that allows getting from 80-100 mg of muscle tissues up to 1000 ng mtDNA, almost free from impurities of RNA and fragments of the nuclear genome.To assess the degree of purity of human mtDNA fraction from impurities of the nuclear genome, we adapted the PCR-screening technique7for the beta-actin gene region and AluSx-repeats in the human genome.

This methodology avoids false-heteroplasmy calls (PCR biases or NUMT contamination) that occur when long-range PCR amplification is used for mtDNA enrichment.
Improved N- and O-Glycopeptide Identification using High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS)
Authors: Alagesan Kathirvel , Ahmed-Begrich Rina , Charpentier Emmanuelle
Published: December 2022

Abstract

Mass spectrometry is the premier tool for identifying and quantifying site-specific protein glycosylation globally. Analysis of intact glycopeptides often requires an enrichment step, after which the samples remain highly complex and exhibit a broad dynamic range of abundance.

Here, we evaluated the analytical benefits of high-field asymmetric waveform ion mobility spectrometry (FAIMS) coupled to nano-liquid chromatography mass spectrometry (nLC-MS) for analyses of intact glycopeptide devoid of any enrichment step. We compared the effects of compensation voltage on the transmission of N- and O-glycopeptides derived from heterogeneous protein mixtures using two FAIMS devices. We comprehensively demonstrate the performance characteristics of the FAIMS device for glycopeptide analysis and recommend optimal electrode temperature and compensation voltage (CV) settings for N- and O-glycopeptide analysis.

Under optimal CV settings, FAIMS-assisted gas-phase fractionation in conjunction with chromatographic reverse phase separation resulted in a 31% increase in the detection of both N- and O-glycopeptide compared to control experiments without FAIMS. Overall, our results demonstrate that FAIMS provides an alternative means to access glycopeptides without any enrichment providing an unbiased global glycoproteome landscape. In addition, our work provides the framework to verify ‘difficult-to-identify’ glycopeptide features.
marmitedefines a novel conserved neuropeptide family mediating nutritional homeostasis
Authors: Francisco AP , Tastekin I , Fernandes AB , Ezra-Nevo G , Deplancke B , Oliveira-Maia AJ , Gontijo AM , Ribeiro C
Published: December 2022

Neuropeptides play a key role in regulating physiology and behavior, including feeding. While animals modify their food choices to respond to the lack of specific nutrients, the mechanisms mediating nutrient-specific appetites remain unclear. Here, we identifiedmarmite(mmt), a previously uncharacterizedDrosophila melanogastergene encoding a secreted peptide that controls feeding decisions. We show that bothmmtmutants and neuronal knockdown ofmmtspecifically increased the intake of proteinaceous food, whereas neuronalmmtoverexpression reduced protein appetite.mmtexpression is also higher in animals maintained on amino acid rich food, suggesting thatmmtencodes a protein-specific satiety signal. Mmt is expressed in a small number of neurons in the adult nervous system, with a single pair of neurons modulating protein appetite. Finally, sequence and phylogenetic analysis showed thatmmtis part of an ancient and conserved family of neuropeptides, including the poorly understood vertebrateneuropeptides BandWgenes. Functional experiments showed thatmmtand vertebrateNPBandNPWmodulate food intake in both flies and mice. Therefore, we discovered an ancient family of neuropeptides involved in controlling feeding across phyla.