bluuebunny/crossref_metadata_2025 huggingface dataset:
It's a small world for parasites: evidence supporting the North American invasion of European
Echinococcus multilocularis
Authors: Santa Maria A. , Umhang Gerald , Klein Claudia , Grant Danielle M. , Ruckstuhl Kathreen E. , Musiani Marco , Gilleard John S. , Massolo Alessandro
Published: March 2023

Echinococcus multilocularis
(
Em
), the causative agent of human alveolar echinococcosis (AE), is present in the Holarctic region, and several genetic variants deem to have differential infectivity and pathogenicity. An unprecedented outbreak of human AE cases in Western Canada infected with a European-like strain circulating in wild hosts warranted assessment of whether this strain was derived from a recent invasion or was endemic but undetected. Using nuclear and mitochondrial markers, we investigated the genetic diversity of
Em
in wild coyotes and red foxes from Western Canada, compared the genetic variants identified to global isolates and assessed their spatial distribution to infer possible invasion dynamics. Genetic variants from Western Canada were closely related to the original European clade, with lesser genetic diversity than that expected for a long-established strain and spatial genetic discontinuities within the study area, supporting the hypothesis of a relatively recent invasion with various founder events.
Styxl2 regulatesde novosarcomere assembly by binding to non-muscle myosin IIs and promoting their degradation
Authors: Chen Xianwei , Li Yanfeng , Xu Jin , Cui Yong , Wu Qian , Yin Haidi , Li Yuying , Gao Chuan , Jiang Liwen , Wang Huating , Wen Zilong , Yao Zhongping , Wu Zhenguo
Published: March 2023

Styxl2, a poorly characterized pseudophosphatase, was identified as a transcriptional target of the Jak1-Stat1 pathway during myoblast differentiation in culture. Styxl2 is specifically expressed in vertebrate striated muscles. By gene knockdown or genetic knockout, we found that Styxl2 plays an essential role in maintaining sarcomere integrity in developing muscles of both zebrafish and mice. To further reveal the functions of Styxl2 in adult muscles, we generated two inducible knockout mouse models: one withStyxl2being deleted in mature myofibers to assess its role in sarcomere maintenance, and the other in adult muscle satellite cells (MuSCs) to assess its role inde novosarcomere assembly. We find that Styxl2 is not required for sarcomere maintenance but functions inde novosarcomere assembly during injury-induced muscle regeneration. Mechanistically, Styxl2 interacts with non-muscle myosin IIs, enhances their ubiquitination, and targets them for autophagy-dependent degradation. Without Styxl2, the degradation of non-muscle myosin IIs is delayed, which leads to defective sarcomere assembly and force generation. Thus, Styxl2 promotesde novosarcomere assembly by interacting with non-muscle myosin IIs and facilitating their autophagic degradation.
Dynamic regulatory elements in single-cell multimodal data capture autoimmune disease heritability and implicate key immune cell states
Authors: Gupta Anika , Weinand Kathryn , Nathan Aparna , Sakaue Saori ,   Accelerating Medicines Partnership RA/SLE Program and Network, Donlin Laura , Wei Kevin , Price Alkes L. , Amariuta Tiffany , Raychaudhuri Soumya
Published: March 2023

In autoimmune diseases such as rheumatoid arthritis (RA), the immune system attacks host tissues1-3. Developing a precise understanding of the fine-grained cell states that mediate the genetics of autoimmunity is critical to uncover causal disease mechanisms and develop potentially curative therapies. We leveraged multimodal single-nucleus (sn) RNA-seq and ATAC-seq data across 28,674 cells from the inflamed synovium of 12 donors with arthritis to identify accessible regions of chromatin associated with gene expression patterns that reflect cell states. For 12 autoimmune diseases, we discovered that cell-state-dependent (“dynamic”) peaks in immune cell types disproportionately captured heritability, compared to cell-state-invariant (“cs-invariant”) peaks. These dynamic peaks marked regulatory elements associated with T peripheral helper, regulatory T, dendritic, and STAT1+CXCL10+myeloid cell states. We argue that dynamic regulatory elements can help identify precise cell states enriched for disease-critical genetic variation.
Association of SARS-CoV-2 Nucleocapsid Protein Mutations with Patient Demographic and Clinical Characteristics during the Delta and Omicron Waves
Authors: Alsuwairi Feda A. , Alsaleh Asma , Alsanea Madain S. , Al-Qahtani Ahmed A. , Obeid Dalia , Almaghrabi Reem S. , Alahideb Basma M. , AlAbdulkareem Maha A. , Mutabagani Maysoon S. , Althawadi Sahar I. , Altamimi Sara A. , Alshukairi Abeer N. , Alhamlan Fatimah S.
Published: March 2023

SARS-CoV-2 genomic mutations outside the spike protein that may increase transmissibility and disease severity have not been well characterized. This study identified mutations in the nucleocapsid protein and their possible association with patient characteristics. We analyzed 695 samples from patients with confirmed COVID-19 in Saudi Arabia between April 1, 2021, and April 30, 2022. Nucleocapsid protein mutations were identified through whole genome sequencing.Χ2 tests and T tests assessed associations between mutations and patient characteristics. Logistic regression estimated risk of intensive care unit (ICU) admission or death. Of 60 mutations identified, R203K was most common followed by G204R, P13L, and E31del, R32del, and S33del. These mutations were associated with reduced risk of ICU admission. P13L, E31del, R32del, and S33del were also associated with reduced risk of death. By contrast, D63G, R203M, and D377Y were associated with increased risk of ICU admission. Most mutations were detected in the SR-rich region, which was associated with low risk of death. C-tail and central linker regions were associated with increased risk of ICU admission, whereas the N-arm region was associated with reduced ICU admission risk. Some SARS-CoV-2 nucleocapsid amino acid mutations may enhance viral infection and COVID-19 disease severity.
Group A streptococcal meningitis with the M1UKvariant in the Netherlands
Authors: van der Putten Boas C.L. , Vlaminckx Bart J.M. , de Gier Brechje , Freudenburg-de Graaf Wieke , van Sorge Nina M.
Published: March 2023

We analyzed over 40 years of bacteriological surveillance data to reveal a 4-fold increase in Group A streptococcal (GAS) meningitis in 2022 compared to the annual average of 1982-2021 (n=5/year). Already 10 GAS meningitis cases occurred in 2023 (until March 13th). Molecular typing revealed that 25 out-of-29 (86%) isolates received in 2022 and 2023 wereemm1.0 (Figure 1). WGS analysis of 19emm1.0 isolates (2019 until 20thDecember 2022) demonstrated that 15 out-of-19 (79%) isolates belonged to the toxicogenic M1UKlineage. Based on these observations, we urge clinicians to be vigilant regarding clinical sign of meningitis with invasive GAS infections, since this disease manifestation appears to have a higher than expected occurrence due to clonal replacement by the recently-emerged M1UKvariant.
Mixed methods approach to examining the implementation experience of a phone-based health research survey investigating risk factors for SARS-CoV-2 infection in California
Authors: Fukui Nozomi , Li Sophia S. , DeGuzman Jennifer , Myers Jennifer F. , Openshaw John , Sharma Anjali , Watt James , Lewnard Joseph A. , Jain Seema , Andrejko Kristin L. , Pry Jake M. ,   the California COVID-19 Case-Control Study Team
Published: March 2023

Objective

To describe the implementation of a test-negative design case-control study in California during the Coronavirus Disease 2019 (COVID-19) pandemic.

Methods

Between February 24, 2021 - February 24, 2022, 34 interviewers called 38,470 SARS-CoV-2-tested Californians to enroll 1,885 cases and 1,871 controls in a 20-minute telephone survey. We estimated adjusted odds ratios for answering the phone and consenting to participate using mixed effects logistic regression. We used a web-based anonymous survey to compile interviewer experiences.

Results

Cases had 1.29-fold (95% CI: 1.24–1.35) higher adjusted odds of answering the phone and 1.69-fold (1.56–1.83) higher adjusted odds of consenting to participate compared to controls. Calls placed from 4pm to 6pm had the highest adjusted odds of being answered. Interviewers who faced participants with dire need for social services or harassment experienced poor mental health.

Conclusions

We suggest calling during afternoons and allocating more effort towards enrolling controls when designing a case-control study. Remaining adaptive to the dynamic needs of the team is critical to a successful study, especially in a pandemic setting.
An explainable AI approach for discovering social determinants of health and risk interactions for stroke in patients with atrial fibrillation
Authors: Zimmerman Raquel M. , Hernandez Edgar J. , Watkins W. Scott , Blue Nathan , Tristani-Firouzi Martin , Yandell Mark , Steinberg Benjamin A.
Published: March 2023

Atrial fibrillation (AF) leads to significant morbidity and mortality, which is primarily related to stroke despite effective stroke prevention therapies. There remains a critical need for personalized, socially aware, equitable stroke risk prediction among patients with AF to enable optimal implementation of contemporary stroke-prevention therapies. In this brief report, we leverage innovative computational tools and high-quality, extensive data (1.8 m patients, augmented with social determinants of health information) to demonstrate the ability of a unique, explainable AI approach to improve the accuracy and equity of stroke risk prediction. Current risk stratification approaches are blind to social determinants of health and fail to adjust for unique contributions and interactions of variables upon stroke risk. In contrast, our results indicate that social determinants of health can be important modifiers of clinical variables and ultimately stroke risk. We hope that this analysis can provide evidence to drive better, more personalized, and equitable stroke risk stratification and prevention for patients with AF in the future.
The Silver Trauma Review Clinic: A novel model of care to manage non-operative injuries in older patients
Authors: Smyth H , Breslin D , Mullany L , Ramiah V , Riches R , Laguna R , Morgan P , Byrne C
Published: March 2023

Background

Increasing numbers of older patients are presenting to emergency departments(ED) following trauma. These patients require multidisciplinary care that the traditional trauma model fails to provide. A Silver Trauma Review Clinic(STRC) was developed in conjunction with the geriatric, ED and multidisciplinary services to improve the post-discharge care of patients with non-operative traumatic injuries.

We aimed to assess the STRC by reviewing the journey and outcomes of patients who attended the clinic and examining new diagnoses and interventions.

Methods

A retrospective review of electronic chart data was performed on all patients who attended the clinic over the initial 1 year period.

Results

137 patient were reviewed with a median age of 80(IQR 12.5), 69% female. The median clinical frailty scale was 3 with a median time from the patient’s initial ED presentation to clinic of 15 days(IQR 11.25) and median time from initial review to discharge 20 days(IQR 34). 71% of presentations were as a result of falls under 2 metres. Primary injuries were 34% vertebral fractures, 45% limb fracture, 18% thoracic trauma, 11% pelvic trauma with 15% of patients suffering from multiple injuries. Patients attending the STRC had a comprehensive geriatric assessment with abnormal Mini-Cog assessments found in 29%, a new diagnosis of osteoporosis in 43% and orthostatic hypotension diagnosed in 13% of patients. 61% were discharged to primary care, 19% linked into a specialist geriatric clinic.

Conclusion

The STRC is a novel approach allowing timely, patient focused, comprehensive and collaborative trauma care of older patients following non-operative injuries.
Clinical Validity of IntelliSpace Cognition Digital Assessment Platform in Mild Cognitive Impairment
Authors: Huijbers Willem , van Elswijk Gijs , Spaltman Mandy , Cornelis Mike , Schmand Ben , Alnaji Baraa , Yargeau Maxwell , Harlock Sarah , Dorn Ryu P. , Ajtai Bela , Westphal Erica S. , Pinter Nandor
Published: March 2023

Abstract

We evaluated a digital cognitive assessment platform, Philips IntelliSpace Cognition, in a cross-sectional cohort of patients diagnosed with mild cognitive impairment (MCI). Performance on individual neuropsychological tests, cognitive domain scores, and Alzheimer’s disease (AD) specific composite scores in MCI were compared with a cohort of cognitively normal adults (CN). The cohorts were matched for age, sex, and education. The performance on all but two neuropsychological tests was worse in the MCI group. After ranking the cognitive domains by effect size, we found that the memory domain was most impaired, followed by executive functioning. The Early AD/MCI Alzheimer’s Cognitive Composite (EMACC) and Preclinical Alzheimer’s Cognitive Composite (PACC) scores were constructed from the digital tests on Philips IntelliSpace Cognition. Both AD-specific composite scores showed greater sensitivity and specificity than the Mini-Mental State Examination, as well as individual neuropsychological tests and individual cognitive domain scores. Together, these results demonstrate the diagnostic value of Philips IntelliSpace Cognition in patients with MCI.
Spontaneous allelic variant inUsh1gresulting in an expanded phenotype
Authors: Vartanian Vladimir , Krey Jocelyn F. , Chatterjee Paroma , Jones Sherri M. , Curtis Allison , Ryals Renee , Lloyd R. Stephen , Barr-Gillespie Peter G.
Published: March 2023

Strategies to reveal the discovery of the relationships between novel phenotypic behaviors and specific genetic alterations can be achieved via either target-specific, directed mutagenesis or phenotypic selection following random chemical mutagenesis. As an alternative approach, one can exploit deficiencies in DNA repair pathways that are responsible for the maintenance of genetic integrity in response to spontaneously-induced damage. In the genetic background of mice deficient in the DNA glycosylase NEIL1, elevated numbers of spontaneous mutations arise from translesion DNA synthesis past unrepaired, oxidatively-induced base damage. Several litters ofNeil1knockout mice included animals that were distinguished by their backwards-walking behavior in open-field environments, while maintaining frantic forward movements in their home cage environment. Other phenotypic manifestations included swim test failures, head tilting, and circling. Mapping of the mutation that conferred these behaviors revealed the introduction of a stop codon at amino acid 4 of theUsh1ggene; the allele wasUsh1gbw, reflecting the backwards-walking phenotype.Ush1gbw/bwnull mice displayed auditory and vestibular defects that are commonly seen with mutations affecting inner-ear hair-cell function, including a complete lack of auditory brainstem responses and vestibular-evoked potentials. As in other Usher syndrome type I mutant mouse lines, hair-cell phenotypes included disorganized and split hair bundles, as well as altered distribution of proteins for stereocilia that localize to the tips of row 1 or row 2. Disruption to the bundle and kinocilium displacement suggested that USH1G is essential for forming the hair cell’s kinocilial links. Due to the vestibular dysfunction, however, visual behavior as measured with optokinetic tracking could not be assessed inUsh1gbw/bwmice. Consistent with other Usher type 1 models, however,Ush1gbw/bwmice had no substantial retinal degeneration compared toUsh1gbw/+controls out to six months. In contrast to previously-describedUsh1galleles, this new allele provides the first knockout model for this gene.
All about urine: Longitudinal examination of urine pH, specific gravity, proteins, culture, and resistance profiles in healthy dogs
Authors: McGlynn Andrew , Mrofchak Ryan , Madan Rushil , Madden Christopher , Jahid Mohammad Jawad , Mollenkopf Dixie , Wittum Thomas , Justice Sheryl S. , Rudinsky Adam , Hokamp Jessica , Hale Vanessa
Published: March 2023

Background

Urine is routinely evaluated in dogs to assess health. Reference ranges for many urine properties are well established, but the scope of variation in these properties over time within heathy dogs is not well characterized.

Objectives

Longitudinally characterize urine properties in healthy dogs over 3 months.

Animals

Fourteen healthy client-owned dogs.

Methods

Dogs were evaluated for health; then, mid-stream free catch urine was collected from each dog at 12 timepoints: Mornings / afternoons of Days 1, 2, 3; end of Weeks 4, 5, 6, 7 and Months 2 and 3. Urine pH, urine specific gravity (USG), protein, cultures, and antimicrobial resistance profiles were evaluated at each timepoint.

Results

Urine pH varied significantly within and between dogs over time (Friedman’s test: withinp= 0.031; betweenp< 0.005). However, USG, protein, and bacterial richness of urine were consistent within dogs over time, and only varied significantly between dogs (Kruskal-Wallis: between allp< 0.005). Antimicrobial resistant isolates were identified in 13 out of 14 dogs with 71% (34 of 48) of the isolates demonstrating resistance to amoxicillin.

Conclusions and clinical importance

1) Urine pH should be assessed at multiple timepoints via pH meter prior to making clinical decisions. 2) Mid-stream free catch urine from multiple healthy dogs yielded high concentrations of bacteria in culture (>105CFU/mL) and should not be considered the only indicator of urinary tract infection. 3) Bacterial isolates demonstrated widespread resistance to amoxicillin / oxacillin underscoring the need for antimicrobial stewardship.
Development and design of the BELpREG registration system for the collection of real-world data on medication use in pregnancy and mother-infant outcomes
Authors: Sillis Laure , Foulon Veerle , Allegaert Karel , Bogaerts Annick , De Vos Maarten , Hompes Titia , Smits Anne , Van Calsteren Kristel , Verbakel Jan Y , Ceulemans Michael
Published: March 2023

Although medication use during pregnancy is common, most available products lack sufficient safety information. As prospective data collection and perinatal pharmacoepidemiologic research on medication safety in pregnancy did not exist in Belgium yet, the BELpREG data registration system was developed. BELpREG enables comprehensive ‘real-world’ data collection on perinatal medication use and mother-infant outcomes via online questionnaires that are completed by pregnant women every four weeks during pregnancy and in the first eight weeks after childbirth. This paper describes the development and current design of the BELpREG system, including the list of BELpREG variables. To compile this list of variables, relevant documents were explored, followed by consultation of an interdisciplinary expert panel. The included variables were structured in seven categories: 1) Sociodemographic characteristics; 2) Information on the current pregnancy and health status; 3) Maternal-obstetric history; 4) Use of medicines, folic acid / pregnancy vitamins and other health products; 5) Substance use; 6) Pregnancy outcomes; and 7) Neonatal outcomes. An electronic informed consent and linkage to medication databases, with images of drug packages and underlying structured data fields, are built into the system. Data collection has officially started in November 2022. Based on its rigorous design, BELpREG holds the potential to be a successful and sustainable research tool, enabling perinatal pharmacoepidemiologic research in Belgium and beyond.
A MAP kinase cascade broadly regulates development and virulence ofSclerotinia sclerotiorumand can be targeted by HIGS for disease control
Authors: Tian Lei , Li Josh , Xu Yan , Qiu Yilan , Li Xin
Published: March 2023

Sclerotinia sclerotiorumcauses white mold or stem rot in a broad range of economically important plants, bringing significant yield losses worldwide. Host-induced gene silencing (HIGS) has been showing promising effects in controlling many fungal pathogens, includingS. sclerotiorum. However, molecular genetic understanding of signaling pathways involved in its development and pathogenicity is needed to provide effective host-induced gene silencing (HIGS) targets for disease control. Here, by employing a forward genetic screen, we characterized an evolutionarily conserved mitogen-activated protein kinase (MAPK) cascade inS. sclerotiorum, consisting of SsSte50-SsSte11-SsSte7-Smk1, controlling mycelial growth, sclerotia development, compound appressoria formation, virulence, and hyphal fusion. Moreover, disruption of the putative downstream transcription factor SsSte12 led to normal sclerotia but aberrant appressoria formation and host penetration defects, suggestive of diverged regulation downstream of the MAPK cascade. Most importantly, targeting ofSsSte50using host-expressed HIGS double stranded RNA resulted in largely reduced virulence ofS. sclerotiorumonNicotiana benthamianaleaves. Therefore, this MAPK signaling cascade is generally needed for its growth, development, and pathogenesis, and is an ideal HIGS target for mitigating economic damages caused byS. sclerotioruminfection.
Comparison of the stability of Glycoprotein Acetyls and high sensitivity C-reactive protein as markers of chronic inflammation
Authors: Crick Daisy C.P. , Khandaker Golam M , Halligan Sarah L , Burgner David , Mansell Toby , Fraser Abigail
Published: March 2023

Background

It has been suggested that glycoprotein acetyls (GlycA) better reflects chronic inflammation than high sensitivity C-reactive protein (hsCRP), but paediatric/life-course data are sparse.

Method

Using data from the Avon Longitudinal Study of Parents and Children and UK Biobank, we compared short-(over weeks) and long-term (over years) correlations of GlycA and hsCRP, cross-sectional correlations between GlycA and hsCRP, and associations of pro-inflammatory risk factors with GlycA and hsCRP across the life-course.

Results

GlycA showed high short-term (weeks) stability at 15y (r=0.75; 95% CI=0.56, 0.94), 18y (r=0.74; 0.64, 0.85), 24y (r=0.74; 0.51, 0.98) and 48y (r=0.82 0.76, 0.86) and this was comparable to the short-term stability of hsCRP at 24y. GlycA stability was moderate over the long-term, for example between 15y and 18y r=0.52; 0.47, 0.56 and between 15y and 24y r=0.37; 0.31, 0.44. These were larger than equivalent correlations of hsCRP. GlycA and concurrently measured hsCRP were moderately correlated at all ages, for example at 15y (r=0.44; 0.40, 0.48) and at 18y (r=0.55; 0.51, 0.59).

We found similar associations of known proinflammatory factors and inflammatory diseases with GlycA and hsCRP. For example, BMI was positively associated with GlycA (mean difference in GlycA per standard deviation change in BMI=0.08; 95% CI=0.07, 0.10) and hsCRP (0.10; 0.08, 0.11).

Conclusion

This study showed that GlycA has greater long-term stability than hsCRP, however associations of proinflammatory factors with GlycA and hsCRP were broadly similar.

Key messages

- GlycA is a novel composite biomarker of inflammation which may have greater stability compared to commonly used biomarkers of inflammation such as hsCRP.

- GlycA has comparable short-term stability, but greater long-term stability compared to hsCRP.

- The associations between proinflammatory factors and CRP and GlycA are similar.
Impact of COVID-19 pandemic on the etiology and characteristics of community-acquired pneumonia among children requiring bronchoalveolar lavage in northern China
Authors: Liu Rui-han , Zhang Yu-yan , Lu Zhou-hua , Shen Chang-qing , Wang Jin , Zhao Qing , Hou Tong-shu , Niu Feng-hai , Kong Qing-xia , Ning Jun , Yang Lei
Published: March 2023

Background

To investigate the etiology and clinical characteristics of community-acquired pneumonia (CAP) among children requiring bronchoalveolar lavage (BAL) and analyze the impact of the coronavirus disease 2019 (COVID-19) pandemic on the pathogen spectrum and clinical manifestations.

Methods

Children <14 years old hospitalized with CAP requiring BLA were enrolled between February 2019 to January 2020 and August 2021 to July 2022. Multiplex reverse transcription polymerase chain reaction (mRT-PCR) was used for pathogen detection. The demographic and clinical characteristics were compared between different pathogen-type infection groups, and before and during the COVID-19 pandemic.

Results

Pathogen was detected in 91.66% (1363/1487) children.Mycoplasma pneumoniae, adenovirus and human rhinovirus were the most frequently detected pathogens. The frequency of detection of virus infections and co-infections was decreased during the pandemic, but the detection of atypical bacterial infections was increased. The clinical manifestations and the results of CT scans and fiberoptic bronchoscopy showed a significant difference between different types of pathogen infection, and lung inflammation was reduced during the COVID-19 pandemic compared with before the pandemic.

Conclusions

M. pneumoniaeinfection might be the greatest pediatric disease burden leading to CAP in northern China. Wearing masks and social distancing in public places during the COVID-19 pandemic effectively reduced the transmission of respiratory viruses, but it did not reduce the infection rate ofM. pneumoniae. In addition, these interventions significantly reduced lung inflammation in children compared with before the pandemic.
Fine-tuning GPCR-mediated neuromodulation by biasing signaling through different G-protein subunits
Authors: Park Jong-Chan , Luebbers Alex , Dao Maria , Semeano Ana , Papakonstantinou Maria P. , Broselid Stefan , Yano Hideaki , Martemyanov Kirill A. , Garcia-Marcos Mikel
Published: March 2023

GPCRs mediate neuromodulation through activation of heterotrimeric G-proteins (Gαβγ). Classical models depict that G-protein activation leads to a one-to-one formation of Gα-GTP and Gβγ species. Each of these species propagates signaling by independently acting on effectors, but the mechanisms by which response fidelity is ensured by coordinating Gα and Gβγ responses remain unknown. Here, we reveal a paradigm of G-protein regulation whereby the neuronal protein GINIP biases inhibitory GPCR responses to favor Gβγ over Gα signaling. Tight binding of GINIP to Gαi-GTP precludes its association with effectors (adenylyl cyclase) and, simultaneously, with Regulator-of-G-protein-Signaling (RGS) proteins that accelerate deactivation. As a consequence, Gαi-GTP signaling is dampened whereas Gβγ signaling is enhanced. We show that this mechanism is essential to prevent imbalances of neurotransmission that underlie increased seizure susceptibilityin vivo. Our findings reveal an additional layer of regulation within a quintessential mechanism of signal transduction that sets the tone of neurotransmission.
Litter Matters: The Importance of Decomposition Products for Soil Bacterial Diversity and abundance of key groups of the N cycle in Tropical Areas
Authors: Diniz Priscila Pereira , Borges Beatriz Maria Ferrari , Oliveira Aline Pacobahyba de , Coelho Maurício Rizzato , Aragão Osnar Obede da Silva , Ribeiro Thiago Gonçalves , Rocha Fernando Igne , Alves Bruno José Rodrigues , Coelho Márcia Reed Rodrigues , Dias Eustáquio Souza , Cole James R. , Howe Adina Chuang , Tsai Siu Mui , Jesus Ederson da Conceição
Published: March 2023

This study investigated the contribution of soil organic layers to bacterial diversity evaluations. We used a forest in the eastern Amazon and an adjacent pasture as model systems. Distinct organic and organo-mineral layers were identified in the forest and pasture floors, including the litter, partially and wholly decomposed organic material, and the mineral and rhizospheric soils. DNA was extracted, and 16S rRNA gene sequencing and qPCR were performed to assess bacterial community structure and the abundance of critical groups of the N cycle. We observed a clear vertical gradient in bacterial community composition. Species followed a log-normal distribution, with the highest richness and diversity observed in transitional organic layers of both land uses. Generally, critical groups of the N cycle were more abundant in these transitional layers, especially in the pasture’s fragmented litter and in the forest’s partially decomposed organic material. Considering the organic layers increased diversity estimates significantly, with the highest alpha and gamma bacterial diversity observed on the pasture floor and the highest beta diversity on the forest floor. The results show that organic layers harbor significant bacterial diversity in natural and anthropized systems and suggest that they can be crucial for maintaining the N cycle in these ecosystems, highlighting the need to consider them when studying soil bacterial diversity.
A Comparison of Deep Learning Architectures for Inferring Parameters of Diversification Models from Extant Phylogenies
Authors: Lajaaiti Ismaël , Lambert Sophia , Voznica Jakub , Morlon Hélène , Hartig Florian
Published: March 2023

Abstract

To infer the processes that gave rise to past speciation and extinction rates across taxa, space and time, we often formulate hypotheses in the form of stochastic diversification models and estimate their parameters from extant phylogenies using Maximum Likelihood or Bayesian inference. Unfortunately, however, likelihoods can easily become intractable, limiting our ability to consider more complicated diversification processes. Recently, it has been proposed that deep learning (DL) could be used in this case as a likelihood-free inference technique. Here, we explore this idea in more detail, with a particular focus on understanding the ideal network architecture and data representation for using DL in phylogenetic inference. We evaluate the performance of different neural network architectures (DNN, CNN, RNN, GNN) and phylogeny representations (summary statistics, Lineage Through Time or LTT, phylogeny encoding and phylogeny graph) for inferring rates of the Constant Rate Birth-Death (CRBD) and the Binary State Speciation and Extinction (BISSE) models. We find that deep learning methods can reach similar or even higher accuracy than Maximum Likelihood Estimation, provided that network architectures and phylogeny representations are appropriately tuned to the respective model. For example, for the CRBD model we find that CNNs and RNNs fed with LTTs outperform other combinations of network architecture and phylogeny representation, presumably because the LTT is a sufficient and therefore less redundant statistic for homogenous BD models. For the more complex BiSSE model, however, it was necessary to feed the network with both topology and tip states information to reach acceptable performance. Overall, our results suggest that deep learning provides a promising alternative for phylogenetic inference, but that data representation and architecture have strong effects on the inferential performance.
Hepatic stellate cells maintain liver homeostasis through paracrine neurotrophin-3 signaling
Authors: Trinh Vincent Quoc-Huy , Lee Ting-Fang , Lemoinne Sara , Ray Kevin C. , Ybanez Maria D. , Tsuchida Takuma , Carter James K. , Agudo Judith , Brown Brian D. , Akat Kemal M. , Friedman Scott L. , Lee Youngmin A.
Published: March 2023

Organ homeostasis is maintained by regulated proliferation of distinct cell populations. In mouse liver, cyclin D1-positive hepatocytes in the midlobular zone repopulate the parenchyma at a constant rate to preserve liver homeostasis. The mitogenic cues that underlie this process are unknown. Hepatic stellate cells, the liver’s pericytes, are in close proximity to hepatocytes and have been implicated in supporting hepatocyte proliferation, but their role in liver homeostasis is unknown. Here, we employ a T cell-mediated hepatic stellate cell ablation model to remove nearly all hepatic stellate cells in the murine liver, enabling the unbiased characterization of hepatic stellate cell functions. In the normal murine liver, complete loss of hepatic stellate cells persists for up to 6 weeks and reduces liver mass. Our results show that hepatic stellate cells induce cyclin D1 in midlobular hepatocytes by release of neurotrophin-3 to promote hepatocyte proliferation via tropomyosin receptor kinase B signaling. These findings establish that hepatic stellate cells form the niche for midlobular hepatocytes and reveal a novel hepatocyte growth factor signaling pathway.

One-Sentence Summary

Hepatic stellate cells provide mitogenic cues for midlobular hepatocyte proliferation and metabolic zonation by secreting neurotrophin-3.
Regulatory sites of CaM-sensitive adenylyl cyclase AC8 revealed by cryo-EM and structural proteomics
Authors: Khanppnavar Basavraj , Schuster Dina , Lavriha Pia , Uliana Federico , Özel Merve , Mehta Ved , Leitner Alexander , Picotti Paola , Korkhov Volodymyr M.
Published: March 2023

Membrane adenylyl cyclase AC8 is regulated by G proteins and calmodulin (CaM), mediating the crosstalk between the cAMP pathway and Ca2+signalling. Despite the importance of AC8 in physiology, including cognitive functions and memory, the structural basis of its regulation by G proteins and CaM is not well defined. Here we report the 3.5 Å resolution cryo-EM structure of the bovine AC8 bound to Ca2+/CaM and the stimulatory Gαs protein. The structure reveals the architecture of the ordered AC8 domains bound to Gαs and a small molecule activator forskolin. The extracellular surface of AC8 features a negatively charged pocket, a potential site for unknown interactors. Despite the well resolved forskolin density, the captured state of AC8 does not favour tight nucleotide binding. The structural proteomics approaches, limited proteolysis and crosslinking mass spectrometry, allow us to identify the contact sites between AC8 and its regulators, CaM, Gαs, and Gβγ, as well as to infer the conformational changes induced by these interactions. Our results provide a framework for understanding the role of flexible regions in the mechanism of AC regulation.
An 11-point time course midgut transcriptome across 72 h after blood feeding provides detailed temporal resolution of transcript expression in the arbovirus vector,Aedes aegypti
Authors: Tsujimoto Hitoshi , Adelman Zach N.
Published: March 2023

As the major vector for dengue, Zika, yellow fever, and chikungunya viruses, the mosquitoAedes aegyptiis one of the most important insects in public health. These viruses are transmitted by bloodfeeding, which is also necessary for the reproduction of the mosquito. Thus, the midgut plays an essential role in mosquito physiology as the center for bloodmeal digestion and as an organ that serves as the first line of defense against viruses. Despite its importance, transcriptomic dynamics with fine temporal resolution across the entire digestion cycle have not yet been reported. To fill this gap, we conducted a transcriptomic analysis ofAe. aegyptifemale midgut across a 72-h bloodmeal digestion cycle for 11 time points with a particular focus on the first 24 h. PCA analysis confirmed that 72 h is indeed a complete digestion cycle. Cluster and GO enrichment analysis showed the orchestrated modulation of thousands of genes to accomplish the midgut’s role as the center for digestion as well as nutrient transport with a clear progression with sequential emphasis on transcription, translation, energy production, nutrient metabolism, transport, and finally autophagy by 24-36hr. We further determined that many serine proteases are robustly expressed as if to prepare for unexpected physiological challenges. This study provides a powerful resource for the analysis of genomic features that coordinate the rapid and complex transcriptional program induced by mosquito bloodfeeding.
A Non-parametric Approach to the Construction of Life Tables at the Local Level with Application to Andhra Pradesh, India
Authors: Chaurasia Aalok Ranjan
Published: March 2023

In this paper, a non-parametric approach has been proposed for the construction of life table at the local level. The approach is based on the non-parametric modelling of the transition in age-specific probabilities of death at higher levels of administration and the relationship between the geometric mean of the age-specific probabilities of death and the probability of death in the first five years of life. The application of the approach has been demonstrated by constructing life tables for the districts of Andhra Pradesh, India using the data from the 2011 population census and the sample registration system.
Tau protein aggregation associated with SARS-CoV-2 main protease
Authors: Eberle Raphael Josef , Coronado Mônika Aparecida , Gering Ian , Korostov Karolina , Stefanski Anja , Stühler Kai , Kraemer-Schulien Victoria , Blömeke Lara , Bannach Oliver , Willbold Dieter
Published: March 2023

The primary function of virus proteases is the proteolytic processing of the viral polyprotein. These enzymes can also cleave host cell proteins, which is important for viral pathogenicity, modulation of cellular processes, viral replication, the defeat of antiviral responses and modulation of the immune response. It is known that COVID-19 can influence multiple tissues or organs and that infection can damage the functionality of the brain in multiple ways. After COVID-19 infections, amyloid-β, neurogranin, tau and phosphorylated tau were detected extracellularly, implicating possible neurodegenerative processes.

The present study describes the possible induction of protein aggregation by the SARS-CoV-2 3CL protease (3CLpro) possibly relevant in neuropathology, such as aggregation of tau, alpha-synuclein and TPD-43. Further investigations demonstrated that tau was proteolytically cleaved by the viral protease 3CL and, consequently, generated aggregates. However, more evidence is needed to confirm that COVID-19 is able to trigger neurodegenerative diseases.
Relict duck-billed dinosaurs survived into the last age of the dinosaurs in subantarctic Chile
Authors: Alarcón-Muñoz Jhonatan , Vargas Alexander O. , Püschel Hans , Soto-Acuña Sergio , Manríquez Leslie , Leppe Marcelo , Kaluza Jonatan , Milla Verónica , Simon-Gutstein Carolina , Palma-Liberona José , Stinnesbeck Wolfgang , Frey Eberhard , Pino Juan Pablo , Bajor Dániel , Núñez Elaine , Ortiz Héctor , Mansilla Héctor , Rubilar-Rogers David , Cruzado-Caballero Penélope
Published: March 2023

In the dusk of the dinosaur era, the advanced duck-billed dinosaurs (Family Hadrosauridae) are thought to have outcompeted other herbivores, making ecosystems less diverse and more vulnerable to the Cretaceous-Paleogene asteroid impact. They were also among the first terrestrial organisms to disperse from North America into South America. Here, we present the first new species of subantarctic duck-billed dinosaur, CPAP 3054, of early Maastrichtian age in Magallanes, Chile. Surprisingly, unlike duckbills further north in Patagonia, CPAP 3054 is not an advanced duckbill, but descends from North American forms that were transitional to Hadrosauridae, diverging shortly before the origin of this family. In North America, these forms were replaced by hadrosaurids in the late Campanian. The survival into the Maastrichtian of a pre-hadrosaurid lineage suggests the ancestors of CPAP 3054 arrived earlier in South America than the hadrosaurids, reaching further south before the Cretaceous-Paleogene mass extinction, where they avoided competition from hadrosaurids.

Additional note

This work contains a new biological name. New names in preprints are not considered available by the ICZN. To avoid ambiguity, the new biological name is not included in this preprint, and the holotype specimen number CPAP 3054 is used as a placeholder. Paratypes described in this preprint are also used in the diagnosis.
Post-COVID-19 syndrome and related dysautonomia reduce quality of life, and increase anxiety and depressive symptoms: evidence from Greece
Authors: Galanis Petros , Katsiroumpa Aglaia , Vraka Irene , Kosiara Katerina , Siskou Olga , Konstantakopoulou Olympia , Katsoulas Theodoros , Gallos Parisis , Kaitelidou Daphne
Published: March 2023

Background

Post-COVID-19 syndrome affects a significant number of SARS-CoV-2 infected individuals even asymptomatic cases causing several neurological and neuropsychiatric symptoms and signs.

Materials and Methods

An online cross-sectional study with a convenience sample was conducted in Greece from November 2022 to January 2023. We measured demographic and clinical characteristics of patients, post-COVID-19 dysautonomia, quality of life with the EQ-5D-3L, and anxiety and depressive symptoms with the Patient Health Questionnaire-4.

Results

Study population included 122 patients with post-COVID-19 syndrome. One out of four patients (27.8%) manifested post-COVID-19 dysautonomia, while mean duration of COVID-19 symptoms was 11.6 months. Anxiety and depressive symptoms were worse after the post-COVID-19 syndrome (p<0.001 in both cases). A statistically significant reduction in quality of life was observed among patients after the post-COVID-19 syndrome (p<0.001 for both EQ-5D-3L index value and EQ-5D-3L VAS). Post-COVID-19 dysautonomia increased depression symptoms after the post-COVID-19 syndrome (p=0.02). We found a negative relationship between duration of COVID-19 symptoms and quality of life (p<0.001). Moreover, our results showed that depressive symptoms were more often among females after the post-COVID-19 syndrome (p=0.01). Also, quality of life was lower among females than males (p=0.004 for EQ-5D-3L index value, and p=0.007 for EQ-5D-3L VAS).

Conclusions

Our results suggest that post-COVID-19 syndrome causes a tremendous impact on patients’ quality of life and mental health. In addition, we found that the groups most psychologically affected were patients with post-COVID-19 dysautonomia, females, and patients with longer duration of symptoms. Policy makers should attach priority to vulnerable groups in future psychiatric planning. Policy measures should focus on mental health of post-COVID-19 patients who seem to be particularly vulnerable.
The impact of blinding on trial results: A systematic review and meta-analysis
Authors: Pitre Tyler , Kirsh Sarah , Jassal Tanvir , Anderson Mason , Padoan Adelia , Xiang Alexander , Mah Jasmine , Zeraatkar Dena
Published: March 2023

Background

Blinding—the concealment of the arm to which participants have been randomized—is an important consideration for assessing risk of bias of randomized trials. A growing body of evidence has, however, yielded inconsistent results on whether trials without blinding produce biased findings.

Objective

To conduct a systematic review and meta-analysis of the evidence addressing whether trials with and without blinding produce different results.

Methods

We searched MEDLINE, EMBASE, Cochrane Reviews, JBI EBP, and Web of Science, from inception to May 2022, for studies comparing the results of trials with and without blinding. Pairs of reviewers, working independently and in duplicate, reviewed search results for eligible studies and extracted data.

We pooled the results of studies comparing trials with and without blinding of patients, healthcare providers/investigators, and outcome assessors/adjudicators using frequentist random-effects meta-analyses. We coded study results such that a ratio of odds ratio (ROR) < 1 and difference in standardized mean difference (dSMD) < 0 indicate that trials without blinding overestimate treatment effects.

Results

We identified 47 eligible studies. For dichotomous outcomes, we found low certainty evidence that trials without blinding of patients and healthcare providers, outcome assessors/adjudicators, and patients may slightly overestimate treatment effects. For continuous outcomes, we found low certainty evidence that trials without blinding of outcome assessors/adjudicators and patients may slightly overestimate treatment effects.

Conclusion

Our systematic review and meta-analysis suggests that blinding may influence trial results in select situations—albeit the findings are of low certainty and the magnitude of effect is modest. In the absence of high certainty evidence suggesting that trials with and without blinding produce similar results, investigators should be cautious about interpreting the results of trials without blinding.
Very early neurological deterioration after thrombolysis in patients with acute ischemic stroke
Authors: Shen Ying-Chi , Yeh Shin-Joe , Chen Chih-Hao , Tang Sung-Chun , Tsai Li-Kai , Jeng Jiann-Shing
Published: March 2023

Background

Early neurological deterioration within 24 h after thrombolysis in patients with acute ischemic stroke (AIS) is associated with poor outcomes. Evidence is lacking regarding neurological deterioration within 1 h after thrombolysis.

Methods

Patients who received intravenous thrombolysis with tissue plasminogen activator (tPA) for AIS between January 2018 and December 2021 were consecutively enrolled. Very early neurological deterioration (VEND) was defined as a ≥ 4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score within 1 h after starting thrombolysis compared with the pre-treatment score. A modified Rankin Scale score of 3–6 at 3 months was defined as a poor functional outcome.

Results

Of the 353 AIS patients (age 69.7 ± 13.3 years, 57% men) receiving thrombolysis with tPA, 29 (8.4%) had VEND. VEND was associated with symptomatic intracranial atherosclerotic disease (ICAD) (41% vs. 17%,P= 0.005) and was an independent predictor of poor functional outcomes at 3 months (adjusted odds ratio 3.04,P= 0.043). The VEND group had higher NIHSS scores at 1 h (19.2 ± 7.3 vs. 9.0 ± 7.1,P< 0.001) and 24 h (14.1 ± 9.8 vs. 7.3 ± 7.5,P= 0.001) after initiating tPA than the non-VEND group. In patients with an initial NIHSS score < 6, VEND was significantly associated with ICAD, receiving endovascular thrombectomy (EVT), and poor functional outcomes. In patients with VEND, EVT with successful recanalization led to lower NIHSS scores at 24 h than in those without successful recanalization (12 ± 9 vs. 26 ± 7,P= 0.047), and 24-h NIHSS scores predicted poor functional outcomes.

Conclusions

In patients receiving thrombolysis, VEND was independently associated with poor functional outcomes. Identifying VEND is crucial for underlying ICAD and salvageability by EVT. Successful recanalization by EVT effectively reduced 24-h stroke severity in patients with VEND.