bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological and Genetic Characterization of Physostegia Chlorotic Mottle Virus in Europe Based on Host Range, Location, and Time
Authors: Temple Coline , Blouin Arnaud G. , De Jonghe Kris , Foucart Yoika , Botermans Marleen , Westenberg Marcel , Schoen Ruben , Gentit Pascal , Visage Michèle , Verdin Eric , Wipf-Scheibel Catherine , Ziebell Heiko , Gaafar Yahya Z. A. , Zia Amjad , Yan Xiao-Hua , Richert-Pöggeler Katja R. , Ulrich Roswitha , Rivarez Mark Paul S. , Kutnjak Denis , Vučurović Ana , Massart Sébastien 
Published: April 2022

Application of high throughput sequencing (HTS) technologies enabled the first identification of Physostegia chlorotic mottle virus (PhCMoV) in 2018 in Austria. Subsequently, PhCMoV was detected in Germany and Serbia on tomatoes showing severe fruit mottling and ripening anomalies. We report here how prepublication data-sharing resulted in an international collaboration across eight laboratories in five countries, enabling an in-depth characterization of PhCMoV. The independent studies converged toward its recent identification in eight additional European countries and confirmed its presence in samples collected 20 years ago (2002). The natural plant host range was expanded from two to nine species across seven families, and we confirmed the association of PhCMoV presence with severe fruit symptoms on economically important crops such as tomato, eggplant, and cucumber. Mechanical inoculations of selected isolates in the greenhouse established the causality of the symptoms on a new indexing host range. In addition, phylogenetic analysis showed a low genomic variation across the 29 near-complete genome sequences available. Furthermore, a strong selection pressure within a specific ecosystem was suggested by nearly identical sequences recovered from different host plants through time. Overall, this study describes the European distribution of PhCMoV on multiple plant hosts, including economically important crops on which the virus can cause severe fruit symptoms. This work demonstrates how to efficiently improve knowledge on an emergent pathogen by sharing HTS data and provides a solid knowledge foundation for further studies on plant rhabdoviruses.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Prenatal Exposure to Insecticides and Weight Trajectories Among South African Children in the VHEMBE Birth Cohort
Authors: Kim Joanne , Yang Seungmi , Moodie Erica E. M. , Obida Muvhulawa , Bornman Riana , Eskenazi Brenda , Chevrier Jonathan 
Published: April 2022

Background:
Dichlorodiphenyltrichloroethane (DDT) or pyrethroid insecticides are sprayed inside dwellings for malaria vector control, resulting in high exposure to millions of people, including pregnant women. These chemicals disrupt endocrine function and may affect child growth. To our knowledge, few studies have investigated the potential impact of prenatal exposure to DDT or pyrethroids on growth trajectories.

Methods:
We investigated associations between gestational insecticide exposure and child growth trajectories in the Venda Health Examination of Mothers, Babies and their Environment, a birth cohort of 751 children born between 2012 and 2013 in South Africa. Based on child weight measured at follow-up and abstracted from medical records, we modeled weight trajectories from birth to 5 years using SuperImposition, Translation and Rotation, which estimated two child-specific parameters: size (average weight) and tempo (age at peak weight velocity). We estimated associations between peripartum maternal concentrations of serum DDT, dichlorodiphenyldichloroethylene, or urinary pyrethroid metabolites and SuperImposition, Translation and Rotation parameters using marginal structural models.

Results:
We observed that a 10-fold increase in maternal concentrations of the pyrethroid metabolite trans-3-(2,2,-dicholorvinyl)-2,2-dimethyl-cyclopropane carboxylic acid was associated with a 21g (95% confidence interval = −40, −1.6) smaller size among boys but found no association among girls (P
interaction = 0.07). Estimates suggested that pyrethroids may be associated with earlier tempo but were imprecise. We observed no association with serum DDT or dichlorodiphenyldichloroethylene.

Conclusions:
Inverse associations between pyrethroids and weight trajectory parameters among boys are consistent with hypothesized disruption of androgen pathways and with our previous research in this population, and support the endocrine-disrupting potential of pyrethroids in humans.
Cresting mortality: Defining a plateau in ongoing massive transfusion
Authors: Quintana Megan T. , Zebley James A. , Vincent Anita , Chang Parker , Estroff Jordan , Sarani Babak , Forssten Maximilian Peter , Cao Yang , Chen Michelle , Corrado Colleen , Mohseni Shahin 
Published: April 2022

BACKGROUND
Blood-based balanced resuscitation is a standard of care in massively bleeding trauma patients. No data exist as to when this therapy no longer significantly affects mortality. We sought to determine if there is a threshold beyond which further massive transfusion will not affect in-hospital mortality.

METHODS
The Trauma Quality Improvement database was queried for all adult patients registered between 2013 and 2017 who received at least one unit of blood (packed red blood cell) within 4 hours of arrival. In-hospital mortality was evaluated based on the total transfusion volume (TTV) at 4 hours and 24 hours in the overall cohort (OC) and in a balanced transfusion cohort, composed of patients who received transfusion at a ratio of 1:1 to 2:1 packed red blood cell to plasma. A bootstrapping method in combination with multivariable Poisson regression was used to find a cutoff after which additional transfusion no longer affected in-hospital mortality. Multivariable Poisson regression was used to control for age, sex, race, highest Abbreviated Injury Scale score in each body region, comorbidities, advanced directives limiting care, and the primary surgery performed for hemorrhage control.

RESULTS
The OC consisted of 99,042 patients, of which 28,891 and 30,768 received a balanced transfusion during the first 4 hours and 24 hours, respectively. The mortality rate plateaued after a TTV of 40.5 units (95% confidence interval [CI], 40–41) in the OC at 4 hours and after a TTV of 52.8 units (95% CI, 52–53) at 24 hours following admission. In the balanced transfusion cohort, mortality plateaued at a TTV of 39 units (95% CI, 39–39) and 53 units (95% CI, 53–53) at 4 hours and 24 hours following admission, respectively.

CONCLUSION
Transfusion thresholds exist beyond which ongoing transfusion is not associated with any clinically significant change in mortality. These TTVs can be used as markers for resuscitation timeouts to assess the plan of care moving forward.

LEVEL OF EVIDENCE
Prognostic and epidemiological, Level III.
SARS-CoV-2 and Liver Transplant: How Has It Behaved in This Sixth Wave?
Authors: Odriozola Aitor , San Segundo David , Cuadrado Antonio , Hernáez Tania , Escrich Víctor , Fortea José Ignacio , Martínez Ángela , Puente Ángela , Lapeña Berta , del Barrio María , López-Hoyos Marcos , Crespo Javier , Fábrega Emilio 
Published: April 2022

Background.
Since the declaration of a new variant of concern (VOC), Omicron, by the World Health Organization in November 2021, a quick spread has been documented worldwide, being the main VOC in the sixth wave in Spain. The Omicron variant has more transmissibility, lower virulence, and less risk of severe disease than previously described VOC. Here we analyze the current wave of severe acute respiratory syndrome coronavirus 2 infection in liver transplant recipients (LTRs).

Methods.
A retrospective observational study of 355 LTRs was conducted in La Rioja and Cantabria regions of Spain. Epidemiological and clinical parameters were gathered on the basis of clinical records and telephone interviews.

Results.
In the current wave of infection, a higher number of LTRs have been found to be infected than the sum of the previous 5 waves (30 versus 16 LTRs). Of the 30 infected LTRs, 29 (96.6%) had received 3 vaccine doses (mRNA based), in a median of 93 d (interquartile range, 86–108) before infection. Eight of 30 LTRs (24.0%) were asymptomatic and 21 LTRs (67.8%) were with mild symptoms with a mean duration of 4.6 d (interquartile range, 2.5–7), whereas in the unvaccinated LTRs, the symptoms were fever, nausea, vomiting, and diarrhea. Moreover, in the sixth wave, intrafamiliar transmission was the main route of infection (17/30; 56.6%), and nosocomial transmission was confirmed in 2 LTRs (6.6%).

Conclusions.
In our series, increased transmissibility of the Omicron variant was confirmed, including nosocomial infection, with a lower risk of severe disease in LTRs. These findings could be supported by the universal vaccination of LTRs and less virulence of the Omicron variant.
Electrographic Features of Epilepsy With Eyelid Myoclonia With Photoparoxysmal Responses
Authors: Zawar Ifrah , Shreshtha Bijina , Benech Daniela , Burgess Richard C. , Bulacio Juan , Knight Elia M. Pestana 
Published: April 2022

Purpose:
Epilepsy with eyelid myoclonia (EMA) is characterized by eyelid myoclonia, eyelid closure sensitivity, and photosensitivity. EEG may manifest with frontal-predominant (FPEDs) or occipital-predominant epileptiform discharges (OPEDs). Data on clinical and electrographic features of these two subtypes are lacking. The purpose of our research was to look at baseline electroclinical features of EMA subtypes and to study electrographic findings of patients with EMA during intermittent photic stimulation (IPS).

Methods:
We retrospectively identified all patients who had photoparoxysmal responses on EEGs performed at Cleveland clinic between January 01, 2012, and December 31, 2019. Patients who met diagnostic criteria for EMA were studied further.

Results:
Of the 249 patients with photoparoxysmal responses, 70 (28.1%) had EMA (62 [88.6%] female; the mean age of epilepsy onset: 7.0 ± 7.9 years). Patients with EMA had either FPEDs or OPEDs. Eleven patients with EMA (15.7%) had seizures (4 absence, 5 myoclonic and 2 bilateral tonic-clonic) during IPS. Patients with OPEDs were more likely to have drug-resistant epilepsy; occipital focal IEDs and other focal IEDs (other than frontal/occipital) on baseline EEG; and generalized IEDs with occipital predominance, generalized IEDs with no predominance, or focal IEDs during IPS. Predictors of seizure occurrence during photic stimulation included the presence of focal occipital IEDs on baseline EEG, generalized IEDs with frontal predominance during IPS, and photoparoxysmal response outlasting the stimulus.

Conclusions:
Our study provides evidence that EMA has two distinct subtypes, which differ in clinical characteristics, baseline EEG, and EEG during photic stimulation. We highlight diagnostic and prognostic implications of these findings. Our study also details EEG characteristics of patients with EMA during IPS.
One-year results of long femoropopliteal lesions stenting with fasciotomy lamina vastoadductoria
Authors: Cheban Alexey V. , Osipova Olesya S. , Ignatenko Pavel V. , Bugurov Savr V. , Gostev Alexandr A. , Saaya Shoraan B. , Rabtsun Artem A. , Karpenko Andrey A. 
Published: April 2022

AbstractObjectiveFasciotomy can increase the mobility of the superficial femoral artery and reduce the incidence of stent breakage. This study aimed to compare the long-term patency of drug-eluting nitinol stents with and without fasciotomy in patients with prolonged SFA occlusions.MethodsA randomized clinical trial was conducted in 60 (1:1) patients with long femoropopliteal steno-occlusive lesions more than 200 mm. Patients in group 1 (Zilver) underwent recanalization of occlusion of the femoropopliteal artery with stenting. In group 2 (ZilverFas), recanalization of the femoropopliteal occlusion with stenting and fasciotomy of Gunter’s canal were performed. The follow up evaluation of patency at 6, 12 months.Results12-month primary patency in Zilver and ZilverFas groups was 51% and 80%, respectively (p = 0.02). The freedom from target revascularization (TLR) in Zilver and ZilverFas groups was 50% and 76%, respectively (p = 0.04). At one-years, primary-assisted and secondary patency for the ZilverFas and Zilver groups were 83% versus 62% (p = 0.07), 86% versus 65% (p = 0.05), respectively. In groups Zilver and ZilverFas, the number of stents fracture was 14 and 7, respectively (p = 0.05). The Cox multivariables regression indicated that the stent fracture, diabetes mellitus were the independent predictor of restenosis and reocclusion. Fasciotomy reduced the chance of reocclusion and restenosis by 2.94 times.ConclusionsOur study has shown that a decompressing the stented segment with fasciotomy significantly improves the patency of the femoropopliteal segment and significantly reduces the number and severity of stents fractures.
Undernutrition and associated factors among people living with HIV under NACS assessment in Muchinga Province, Zambia, 2019-2020
Authors: Sadoki Ebedy , Kinge Constance Wose , Jojozi Zikhona , Mwansa Grain , Chirwa Ben , Chirowa Frank , Mothibi Eula , Maotoe Thapelo , Magwende George , Shingwe Frank , Sanne Ian , Mwala Philip , Chasela Charles 
Published: April 2022

AbstractIntroductionGood nutrition in People Living with HIV (PLHIV) has a good influence on treatment outcomes and in turn a better quality of life. Despite, the significant role it plays, many patients have limited access to Nutritional Assessment Counselling and Support (NACS). We evaluated undernutrition in people living with HIV and associated factors in Muchinga Province, Zambia, from October 2019 to March 2020.Material and MethodsThis was secondary analysis of routine program data of HIV-positive clients on ART enrolled at EQUIP-supported health facilities in Muchinga. Undernutrition was determined using body mass index (BMI) calculations and classified as undernutrition (<18.5 kg/m2), normal (18.5 – 24.9 kg/m2) or over-nutrition (overweight, 25 – 29.9 kg/m2 and obese, 25 – 29.9 kg/m2). Multivariate-adjusted odds ratios (aOR) were used to assess factors associated with undernutrition.ResultsOf the 506 eligible clients under NACS, the mean age was 34.9 years ± 13.5SD, with 251 (approximately 50%) between the ages of 21 – 39 years. More than half (67%) were females, 284 (56%) were urban residents, and 180 (35.6 %) were unemployed. The majority (approximately 71%) were on the TLE regimen with a median duration on ART treatment of ∼3 years (IQR=1– 6). There were 233 (46%) who had a normal BMI, 191 (37.7%) who had under-nutrition, and 82 (16.2%) who had over-nutrition (9.7% overweight: 6.5% obesity). Clients in the urban area (aOR= 2.0; 95%CI: 1.28 – 3.1), unemployed (aOR= 2.4 (1.18-4.69)2.4; 95%CI: 1.18 – 4.69), married (aOR= 2.3; 95%CI: 1.26 – 4.38) and being on TLD (aOR= 2.8; 95%CI: 1.23 – 6.23) were more likely to be under-nourished.ConclusionNACS played a vital role in identifying HIV-positive clients who required more specialized care for improved clinical health outcomes. There is a need to strengthen HIV and nutrition integration in low-resourced countries with high HIV burden for improved treatment outcomes and quality of life.
Laboratory-acquired mutations fall outside the wild-type alleleome of Escherichia coli
Authors: Catoiu Edward , Phaneuf Patrick , Monk Jonathan , Palsson Bernhard O 
Published: April 2022

AbstractInexpensive DNA sequencing has led to a rapidly increasing number of whole genome sequences in the public domain. Natural sequence variation can now be assessed across a large number of sequenced strains of a bacterial species, resulting in the definition of the wild-type alleleome (the collection of alleles for every gene found in the species). Concurrently, laboratory evolution emerged as a new approach to address biological questions and to develop new phenotypic traits, and a large number of laboratory acquired mutations can be found in databases. The availability of this large-scale sequence variation data now allows for a detailed comparison of mutations fixed in natural versus laboratory evolutions. Such comparison shows that laboratory-acquired mutations are rarely found in the wild-type alleleome of Escherichia coli. The E. coli alleleome is highly conserved as most of the sequence variation is concentrated in about 2% of the coding region. We find that there are typically two alternate amino acids coded for in the variable locations, and switches between the two are found in the data sets. Finally, we find that adaptive laboratory mutations, unlike wild-type mutations, do not utilize the redundancy built into the genetic code: they are less likely to be synonymous and rely on changing a single nucleotide in a codon. However, the uniqueness of mutations fixed in laboratory evolutions bodes well for synthetic biology by revealing novel exploitable sequence space untouched by natural evolution.
Regression discontinuity design to evaluate the effect of statins on myocardial infarction in electronic health records
Authors: Odden Michelle C. , Zhang Adina , Jawadekar Neal , Tan Annabel , Zeki Al Hazzouri Adina , Calonico Sebastian 
Published: April 2022

ABSTRACTRegression discontinuity design (RDD) is a quasi-experimental method intended for causal inference in observational settings. While RDD is gaining popularity in clinical studies, there are limited real-world studies examining the performance of this approach on estimating known trial-established casual effects. The goal of this paper is to estimate the effects of statins on myocardial infarction (MI) using RDD and propensity score matching. For the regression discontinuity analysis, we leveraged a 2008 guideline in the UK that recommends statins if a patient’s 10-year cardiovascular disease (CVD) risk score >20%. We used UK electronic health record data from the Health Improvement Network on 49,242 patients aged 65+ in 2008-2011 (our study baseline) without a history of CVD and no statin use in the year prior to the CVD risk score assessment. Both the regression discontinuity (n=19,432) and the propensity score matched populations (n=24,814) demonstrated good balance of confounders. Using RDD, the adjusted point estimate for statins on MI was in the protective direction and similar to the statin effect observed in clinical trials, although the confidence interval included the null (HR= 0.8, 95%CI: 0.4, 1.4). Conversely, the adjusted estimates using propensity score matching remained in the harmful direction: HR =2.4 (95%CI:2.0, 3.0). Regression discontinuity appeared superior to propensity score matching in replicating the known protective association of statins with MI, although precision was poor. Our findings suggest that, when used appropriately, regression discontinuity can expand the scope of clinical investigations aimed at causal inference by leveraging treatment rules from everyday clinical practice.
Structure Of Eukaryotic Type III Glutamine Synthetase Lacking Ring-Ring Quaternary Contacts
Authors: Novikova Irina V. , Powell Samantha M. , Smallwood Chuck R. , Purvine Samuel O. , Zhou Mowei , Evans James E. 
Published: April 2022

AbstractThere are three major classes of the enzyme Glutamine Synthetase (GS), denoted as GSI, GSII and GSIII in both prokaryotes and eukaryotes, that share widely conserved active-site residues but vary in average protein length, oligomeric assembly state and cofactor requirements. Key structures have been determined for all prokaryotic and eukaryotic GS classes except the GSIII class of eukaryotic origin, where even basic questions about its functional oligomeric state are unresolved. Here, we report the 3.2Å cryo-EM structure of eukaryotic GSIII from the ancient organism of green algal lineage Ostreococcus tauri. Using a combined structural and biochemical approach, we demonstrate that O. tauri GSIII self-assembles and functions exclusively as a single hexameric ring. This is unlike most GSs in other classes, where they form double-stacked ring assemblies instead. Major structural differences in the ring-ring stacking across the classes suggest evolutionary pressure may have favored higher-order interactions that might be beneficial but are not necessarily required for the catalytic GS performance.
Mouse mutants in schizophrenia risk genes GRIN2A and AKAP11 show EEG abnormalities in common with schizophrenia patients
Authors: Herzog Linnea E. , Wang Lei , Yu Eunah , Choi Soonwook , Farsi Zohreh , Song Bryan , Pan Jen Q. , Sheng Morgan 
Published: April 2022

ABSTRACTBACKGROUNDSchizophrenia is a heterogeneous psychiatric disorder with a strong genetic basis, whose etiology and pathophysiology remain poorly understood. Exome sequencing studies have uncovered rare, loss-of-function variants that greatly increase risk of schizophrenia [1], including loss-of-function mutations in GRIN2A (aka GluN2A or NR2A, encoding the NMDA receptor subunit 2A) and AKAP11 (A-Kinase Anchoring Protein 11). AKAP11 and GRIN2A mutations are also associated with bipolar disorder [2], and epilepsy and developmental delay/intellectual disorder [1, 3, 4], respectively. Accessible in both humans and rodents, electroencephalogram (EEG) recordings offer a window into brain activity and display abnormal features in schizophrenia patients. Does loss of Grin2a or Akap11 in mice also result in EEG abnormalities?METHODSWe monitored EEG in heterozygous and homozygous knockout Grin2a and Akap11 mutant mice compared with their wild-type littermates, at 3- and 6-months of age, across the sleep/wake cycle and during auditory stimulation protocols.RESULTSGrin2a and Akap11 mutants exhibited increased resting gamma power, attenuated 40-50 Hz auditory steady-state responses (ASSR), and reduced responses to unexpected auditory stimuli during mismatch negativity (MMN) tests. Sleep spindle density was reduced in a gene dose-dependent manner in Akap11 mutants, whereas Grin2a mutants showed increased sleep spindle density.CONCLUSIONSThe EEG phenotypes of Grin2a and Akap11 mutant mice show a variety of abnormal features that overlap considerably with human schizophrenia patients, reflecting systems-level changes caused by Grin2a and Akap11 deficiency. These neurophysiologic findings further substantiate Grin2a and Akap11 mutants as genetic models of schizophrenia and identify potential biomarkers for stratification of schizophrenia patients.
Copper binding leads to increased dynamics in the regulatory N-terminal domain of full-length human copper transporter ATP7B
Authors: Orädd Fredrik , Steffen Jonas Hyld , Gourdon Pontus , Andersson Magnus 
Published: April 2022

AbstractATP7B is a human copper-transporting P1B-type ATPase that is involved in copper homeostasis and resistance to platinum drugs in cancer cells. ATP7B consists of a copper-transporting core and a regulatory N-terminal tail that contains six metal-binding domains (MBD1-6) connected by linker regions. The MBDs can bind copper, which changes the dynamics of the regulatory domain and activates the protein, but the underlying mechanism remains unknown. To identify possible copper-specific structural dynamics involved in transport regulation, we constructed a model of ATP7B spanning the N-terminal tail and core catalytic domains and performed molecular dynamics (MD) simulations with (holo) and without (apo) copper ions bound to the MBDs. In the holo protein, MBD2, MBD3 and MBD5 showed enhanced mobilities, which resulted in a more extended N-terminal regulatory region. The observed separation of MBD2 and MBD3 from the core protein supports a mechanism where copper binding activates the ATP7B protein by reducing interactions among MBD1-3 and between MBD1-3 and the core protein. Instead, an increased interaction between MBD5 and the core protein was observed that brought the copper-binding site of MBD5 closer to the high-affinity internal copper-binding site in the core protein. The simulation results assign specific, mechanistic roles to the metal-binding domains involved in ATP7B regulation that are testable in experimental settings.