bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Noninvasive Markers of Steatosis and Liver Fibrosis in Human Immunodeficiency Virus-Monoinfected Patients on Stable Antiretroviral Regimens
Authors: Busca C , Sánchez-Conde M , Rico M , Rosas M , Valencia E , Moreno A , Moreno V , Martín-Carbonero L , Moreno S , Pérez-Valero I , Bernardino J I , Arribas J R , González J , Olveira A , Castillo P , Abadía M , Guerra L , Mendez C , Montes M L
Published: June 2022

Background

Nonalcoholic fatty liver disease (NAFLD) is a major nonacquired immune deficiency syndrome-defining condition for persons with human immunodeficiency virus (PWH). We aimed to validate noninvasive tests for the diagnosis of NAFLD in PWH.

Methods

This is a cross-sectional study of PWH on stable antiretroviral therapy with persistently elevated transaminases and no known liver disease. The area under the receiver operating characteristic curve (AUROC) was calculated to compare the diagnostic accuracy of liver biopsy with abdominal ultrasound, transient elastography (TE) (including controlled attenuation parameter [CAP]), and noninvasive markers of steatosis (triglyceride and glucose index [TyG], hepatic steatosis index [HSI], fatty liver index [FLI]) and fibrosis ([FIB]-4, aminotransferase-to-platelet ratio index [APRI], NAFLD fibrosis score). We developed a diagnostic algorithm with serial combinations of markers.

Results

Of 146 patients with increased transaminase levels, 69 underwent liver biopsy (90% steatosis, 61% steatohepatitis, and 4% F ≥3). The AUROC for steatosis was as follows: ultrasound, 0.90 (0.75–1); CAP, 0.94 (0.88–1); FLI, 0.81 (0.58–1); HSI, 0.74 (0.62–0.87); and TyG, 0.75 (0.49–1). For liver fibrosis ≥F3, the AUROC for TE, APRI, FIB-4, and NAFLD fibrosis score was 0.92 (0.82–1), 0.96 (0.90–1), 0.97 (0.93–1), and 0.85 (0.68–1). Optimal diagnostic performance for liver steatosis was for 2 noninvasive combined models of tests with TyG and FLI/HSI as the first tests and ultrasound or CAP as the second tests: AUROC = 0.99 (0.97–1, P < .001) and 0.92 (0.77–1, P < .001).

Conclusions

Ultrasound and CAP performed best in diagnosing liver steatosis, and FLI, TyG, and HSI performed well. We propose an easy-to-implement algorithm with TyG or FLI as the first test and ultrasound or CAP as the second test to accurately diagnose or exclude NAFLD.
Feasibility of hybrid in-stream generator–photovoltaic systems for Amazonian off-grid communities
Authors: Brown Erik , Johansen Igor Cavallini , Bortoleto Ana Paula , Pokhrel Yadu , Chaudhari Suyog , Cak Anthony , Sulaeman Samer , Castro-Diaz Laura , Lopez Maria Claudia , Mayer Adam , Walgren Judith , Müller Norbert , Moran Emilio
Published: June 2022

While there have been efforts to supply off-grid energy in the Amazon, these attempts have focused on low upfront costs and deployment rates. These “get-energy-quick” methods have almost solely adopted diesel generators, ignoring the environmental and social risks associated with the known noise and pollution of combustion engines. Alternatively, it is recommended, herein, to supply off-grid needs with renewable, distributed microgrids comprised of photovoltaics (PV) and in-stream generators (ISG). Utilization of a hybrid combination of renewable generators can provide an energetically, environmentally, and financially feasible alternative to typical electrification methods, depending on available solar irradiation and riverine characteristics, that with community engagement allows for a participatory codesign process that takes into consideration people’s needs. A convergent solution development framework that includes designers—a team of social scientists, engineers, and communication specialists—and communities as well as the local industry is examined here, by which the future negative impacts at the human–machine–environment nexus can be minimized by iterative, continuous interaction between these key actors.
Comparison of the Biological Characteristics and Molecular Mechanisms of Fludioxonil-Resistant Isolates of Botrytis cinerea from Tomato in Liaoning Province of China
Authors: Chen Le , Sun Baixin , Zhao Yang , Xiang Peng , Miao Zeyan
Published: June 2022

Botrytis cinerea is a common filamentous phytopathogen that causes serious pre- and postharvest losses worldwide. The phenylpyrrole fungicide fludioxonil has been reported to have high activity against B. cinerea and has been applied to control gray mold in tomato. A total of 206 B. cinerea isolates were collected from tomato greenhouses in Liaoning Province, China, in 2016 and 2017, and sensitivity to fludioxonil was demonstrated by discriminatory concentrations. One highly fludioxonil-resistant isolate, 5 medium-fludioxonil-resistance isolates, and 23 low-fludioxonil-resistance isolates were detected in the field. The fludioxonil-resistant isolates were less fit than the sensitive isolates and presented reduced sporulation, pathogenicity, and mycelial growth and hypersensitivity to osmotic stress, even though sclerotium production had no connection with resistance. Positive cross-resistance was observed between fludioxonil and the dicarboximide fungicides procymidone and iprodione but not between fludioxonil and the fungicides boscalid, fluopyram, fluazinam, and pyrimethanil. Sequence alignment of the BcOS1 gene indicated that the observed sensitivity was identical to that of B05.10 and the low-resistance mutant had two types of mutations, F127S+I365N and A1259T. The medium-resistance mutants had only one type of mutation linked with the 3-aa mutant Q369P+N373S+A1259T, and the highly resistant mutant had a 3-aa mutation with I365S+N373S+A1259T. Molecular docking illustrated that all the resistant isolates showed less affinity than the sensitive isolates with fludioxonil.
Catching Spores: Linking Epidemiology, Pathogen Biology, and Physics to Ground-Based Airborne Inoculum Monitoring
Authors: Mahaffee Walter F. , Margairaz Fabien , Ulmer Lucas , Bailey Brian N. , Stoll Rob
Published: June 2022

Monitoring airborne inoculum is gaining interest as a potential means of giving growers an earlier warning of disease risk in a management unit or region. This information is sought by growers to aid in adapting to changes in the management tools at their disposal and the market-driven need to reduce the use of fungicides and cost of production. To effectively use inoculum monitoring as a decision aid, there is an increasing need to understand the physics of particle transport in managed and natural plant canopies to effectively deploy and use near-ground aerial inoculum data. This understanding, combined with the nuances of pathogen-specific biology and disease epidemiology, can serve as a guide to designing improved monitoring approaches. The complexity of any pathosystem and local environment are such that there is not a generalized approach to near-ground air sampler placement, but there is a conceptual framework to arrive at a “semi-optimal” solution based on available resources. This review is intended as a brief synopsis of the linkages among pathogen biology, disease epidemiology, and the physics of the aerial dispersion of pathogen inoculum and what to consider when deciding where to locate ground-based air samplers. We leverage prior work in developing airborne monitoring tools for hops, grapes, spinach, and turf, and research into the fluid mechanics governing particle transport in sparse canopies and urban and forest environments. We present simulation studies to demonstrate how particles move in the complex environments of agricultural fields and to illustrate the limited sampling area of common air samplers.
Strain Tracking of ‘Candidatus Liberibacter asiaticus’, the Citrus Greening Pathogen, by High-Resolution Microbiome Analysis of Asian Citrus Psyllids
Authors: Higgins Steven A. , Mann Marina , Heck Michelle
Published: June 2022

The Asian citrus psyllid, Diaphorina citri, is an invasive insect and a vector of ‘ Candidatus Liberibacter asiaticus’ ( CLas), a bacterium whose growth in Citrus species results in huanglongbing (HLB), also known as citrus greening disease. Methods to enrich and sequence CLas from D. citri often rely on biased genome amplification and nevertheless contain significant quantities of host DNA. To overcome these hurdles, we developed a simple pretreatment DNase and filtration (PDF) protocol to remove host DNA and directly sequence CLas and the complete, primarily uncultivable microbiome from D. citri adults. The PDF protocol yielded CLas abundances upward of 60% and facilitated direct measurement of CLas and endosymbiont replication rates in psyllids. The PDF protocol confirmed our lab strains derived from a progenitor Florida CLas strain and accumulated 156 genetic variants, underscoring the utility of this method for bacterial strain tracking. CLas genetic polymorphisms arising in lab-reared psyllid populations included prophage-encoding regions with key functions in CLas pathogenesis, putative antibiotic resistance loci, and a single secreted effector. These variants suggest that laboratory propagation of CLas could result in different phenotypic trajectories among laboratories and could confound CLas physiology or therapeutic design and evaluation if these differences remain undocumented. Finally, we obtained genetic signatures affiliated with Citrus nuclear and organellar genomes, entomopathogenic fungal mitochondria, and commensal bacteria from laboratory-reared and field-collected D. citri adults. Hence, the PDF protocol can directly inform agricultural management strategies related to bacterial strain tracking, insect microbiome surveillance, and antibiotic resistance screening.
Severe Acute Coronary Syndrome After Carbetocin Injection During Cesarean Delivery: A Case Report
Authors: Crabbe M. , Dangoisse M. , Catry A. , Van der Linden P.
Published: June 2022

(Eur J Anaesthesiol. 2021;38:899–901)

As an analogue of oxytocin the function of carbetocin is similar but has a longer duration of action. This offers the advantage of giving single slow injection of 100 mg for uterotonic effect. The toxicity of carbetocin has not been completely defined and its effective dose, 100 mg, may have been miscalculated. This report reviews the case of a 36-year-old parturient with no cardiovascular risk factors who experienced a severe acute coronary syndrome (ACS) leading to ventricular fibrillation following an injection of carbetocin 30 mg during cesarean delivery (CD).
Twelve-month Treatment Retention and Associated Factors: A Comparison of 2 Medically Assisted Therapy Clinics in Dar es Salaam, Tanzania
Authors: Mlaki Damas A. , Mbwambo Jessie K. , McCurdy Sheryl , Masao Frank A. , Kaduri Pamela A.
Published: June 2022

Objectives

Retention in methadone maintenance treatment is instrumental in achieving better treatment outcomes. In this study, we compared 2 medication-assisted treatment (MAT) clinics in Dar es Salaam, Tanzania with respect to patient characteristics, outcomes, and factors that predict 12-month treatment retention.

Methods

This retrospective registry-based cohort study utilized data collected for routine clinical and program monitoring at 2 sites, Mwananyamala and Muhimbili MAT clinics. Cumulative retention in treatment was calculated using life tables. The analysis of treatment retention predictor variables used both Kaplan-Meier and Cox proportional hazard analyses.

Results

We examined the socio-demographic and program-related characteristics of 362 (181 from each clinic) patients. Twelve-month treatment retention was higher at Mwananyamala (73%) than Muhimbili (64%) MAT clinic, but the difference was not significant. In both clinics, a higher methadone dose (>60mg) significantly predicted treatment retention (P < 0.05). Being employed and traveling an average short distance (<5 km) from home to clinic significantly increased the likelihood of remaining in treatment in Muhimbili MAT clinic (P< 0.05) only.

Conclusions

A methadone dose of 60 mg and above was associated with longer retention in treatment. At 1 clinic in a denser and more central location, employment and a short travel distance from home to clinic were associated with longer tenure in treatment. These findings have potential implications for clinical practice, research, and scaling up MAT services in Tanzania.
Cardiovascular Diseases Risk Predictors: ABO Blood Groups in a Different Role
Authors: Neshat Sina , Rezaei Abbas , Farid Armita , Javanshir Salar , Dehghan Niri Fatemeh , Daneii Padideh , Heshmat-Ghahdarijani Kiyan , Sotoudehnia Korani Setayesh
Published: June 2022

Cardiovascular diseases (CVDs) pose a serious threat to people’s health, with extremely high global morbidity, mortality, and disability rates. This study aimed to review the literature that examined the relationship between blood groups and CVD. Many studies have reported that non-O blood groups are associated with an increased risk and severity of coronary artery disease and acute coronary syndromes. Non-O blood groups increase the risk and severity of these conditions by increasing von Willebrand factor and plasma cholesterol levels and inducing endothelial dysfunction and inflammation. They have also been linked with increased coronary artery calcification, coronary lesion complexity, and poor collateral circulation. Blood groups also affect the prognosis of coronary artery disease and acute coronary syndrome and can alter the rate of complications and mortality. Several cardiovascular complications have been described for coronavirus disease 2019, and blood groups can influence their occurrence. No studies have found a significant relationship between the Lewis blood group and CVD. In conclusion, people with non-O blood groups should be vigilantly monitored for cardiovascular risk factors as prevention and proper treatment of these risk factors may mitigate their risk of CVD and adverse cardiovascular events.
Case Series: Presumed Choroidal Melanoma Diagnosis Expedited by Documented Growth on Serial Optical Coherence Tomography
Authors: O'Day Roderick F. J. , McKay Daniel , McKenzie John D. , van Wijngaarden Peter
Published: June 2022

SIGNIFICANCE

These cases highlight the importance of monitoring choroidal nevi with benign imaging characteristics and the potential to quantify horizontal growth using optical coherence tomography (OCT), in the absence of color fundus photography.

PURPOSE

This study aimed to present reports of two patients with pigmented choroidal tumors with low malignant potential based on their multimodal imaging features at the time of referral, but access to prior OCT imaging confirmed horizontal growth consistent with melanoma.

CASE REPORTS

Two patients with pigmented, dome-shaped, subfoveal tumors were referred. Both tumors had basal diameters greater than 5 mm but no other risk factor for growth at the time of referral. Screening OCT scans had been taken of each patient's macula more than 5 years before referral, but color fundus photography was not available for either. Repeat OCT scanning at the time of referral showed horizontal growth of the tumors consistent with melanoma. As per the “To Find Small Ocular Melanoma—Do Imaging” risk factor assessment, the 5-year risk of growth of both tumors would be estimated at 11% at the time of referral, and in the absence of the documented horizontal growth on OCT scanning, the patients would have been monitored for growth. After discussion of the risks and benefits, both patients elected for their tumors to be managed as choroidal melanomas and underwent ruthenium plaque brachytherapy.

CONCLUSIONS

Horizontal growth of choroidal tumors can be established using sequential OCT scans in the absence of color fundus photography. Access to prior imaging can expedite the diagnosis of choroidal melanoma, potentially allowing patients to be treated earlier.
Case Report: Downbeat Nystagmus Due to Epidural Puncture during Labor with Undiagnosed Arnold-Chiari Malformation
Authors: Bhakhri Raman , Messner Leonard
Published: June 2022

SIGNIFICANCE

Epidural anesthesia is a safe procedure used in pregnant patients during labor. However, caution should be exercised in those patients who have concurrent Arnold-Chiari malformation.

PURPOSE

This study aimed to report a rare and atypical presentation of downbeat nystagmus, in a pregnant patient with Arnold-Chiari malformation type 1 (ACM1), secondary to accidental dural puncture.

CASE REPORT

A 31-year-old African American woman presented with a chief complaint of decreased vision and oscillopsia that occurred after giving birth, 6 months earlier. Her medical history before presentation was unremarkable. Her delivery was typical; however, the patient did receive epidural anesthesia, which resulted in a dural puncture. The patient noted her symptoms a few days after delivery. Upon examination, persistent downbeat nystagmus was noted in both eyes. Magnetic resonance imaging revealed a 2.5-cm inferior displacement of the cerebellar tonsils below the foramen magnum consistent with ACM1. The patient was referred to neurosurgery for posterior fossa decompression. However, surgery was deferred until appropriate weight reduction could be achieved. Follow-up examination 6 months later revealed no change in her clinical findings.

CONCLUSIONS

This case report highlights an atypical presentation of downbeat nystagmus secondary to an accidental dural puncture in a pregnant patient with undiagnosed ACM1. Clinicians should consider the importance of considering ocular complications that can occur in pregnant patients with ACM1. Questioning of women who have recently given birth about epidural anesthesia should be considered with an acute presentation of downbeat nystagmus.
Weight-Based Versus Flat Dosing of Epinephrine During Cardiac Arrest in the PICU: A Multicenter Survey
Authors: Kienzle Martha F. , Morgan Ryan W. , Dewan Maya , Hebbar Kiran B. , Nadkarni Vinay M. , Srinivasan Vijay , Tegtmeyer Ken , Sutton Robert M. , Wolfe Heather A.
Published: June 2022

Objectives:

Pediatric Advanced Life Support (PALS) guidelines include weight-based epinephrine dosing recommendations of 0.01 mg/kg with a maximum of 1 mg, which corresponds to a weight of 100 kg. Actual practice patterns are unknown.

Design:

Multicenter cross-sectional survey regarding institutional practices for the transition from weight-based to flat dosing of epinephrine during cardiopulmonary resuscitation in PICUs. Exploratory analyses compared epinephrine dosing practices with several institutional characteristics using Fisher exact test.

Setting:

Internet-based survey.

Subjects:

U.S. PICU representatives (one per institution) involved in resuscitation systems of care.

Interventions:

None.

Measurements and Main Results:

Of 137 institutions surveyed, 68 (50%) responded. Most responding institutions are freestanding children’s hospitals or dedicated children’s hospitals within combined adult/pediatric hospitals (67; 99%); 55 (81%) are academic and 41 (60%) have PICU fellowship programs. Among respondents, institutional roles include PICU medical director (13; 19%), resuscitation committee member (23; 34%), and attending physician with interest in resuscitation (21; 31%). When choosing between weight-based and flat dosing, 64 respondents (94%) report using patient weight, 23 (34%) patient age, and five (7%) patient pubertal stage. Among those reporting using weight, 28 (44%) switch at 50 to less than 60 kg, 17 (27%) at 60 to less than 80 kg, five (8%) at 80 to less than 100 kg, and eight (12%) at greater than or equal to 100 kg. Among those reporting using age, four (17%) switch at 14 to less than 16 years, five (22%) at 16 to less than 18, and six (26%) at greater than or equal to 18. Twenty-nine respondents (43%) report using ideal body weight when dosing epinephrine in obese patients. Using patient age in choosing epinephrine dosing is more common in institutions that require Advanced Cardiac Life Support (ACLS) certification for some/all code team responders compared with institutions that do not require ACLS certification (52% vs 22%; p = 0.02).

Conclusions:

The majority of PICUs surveyed report epinephrine dosing practices that are inconsistent with PALS guidelines.
Metapredict V2: An update to metapredict, a fast, accurate, and easy-to-use predictor of consensus disorder and structure
Authors: Emenecker Ryan J. , Griffith Daniel , Holehouse Alex S.
Published: June 2022

Intrinsically disordered proteins and protein regions make up 20-40% of most eukaryotic proteomes and play essential roles in a wide gamut of cellular processes, from intracellular trafficking to epigenetic silencing. Given their importance, the ability to robustly, quickly, and easily identify IDRs within large proteins is critical. Here we present metapredict V2, an update to our deep-learning-based disorder predictor metapredict. Metapredict V2 has substantially improved accuracy, more features, and a more user-friendly interface via our web server (https://metapredict.net/), Python package, and command-line tool. To illustrate V2’s improved performance we undertake a systematic analysis of human transcription factors, as well as illustrate that metapredict V2 works well for synthetic or non-natural proteins.

KEY POINTS

Metapredict is a fast and easy-to-use disorder predictor released in 2021.

Metapredict V2 was released in March 2022 and includes improved accuracy and new features.

Metapredict V2 is now the default metapredict implementation, although the original implementation is available as ‘legacy’ metapredict.

This manuscript provides a summary of how we improved the accuracy of metapredict and compares the original version (legacy) to our improved version (V2)

This manuscript will not be submitted to a journal; if you use metapredict V2 please cite the original paper and make reference to the fact that V2 is being used.
Going with the flow – how a stream insect,Pteronarcys californica,exploits local flows to increase oxygen availability
Authors: Birrell Jackson H. , Woods H. Arthur
Published: June 2022

For insects, aquatic life is challenging because oxygen supply is typically low compared to air. Although many insects rely on stream flows to augment oxygen supply, oxygen limitation may occur when oxygen levels or flows are low or when warm temperatures stimulate metabolic demand for oxygen. Behavior may allow insects to mitigate oxygen shortages – by moving to cooler, more oxygenated, or faster flowing microhabitats. However, whether stream insects can make meaningful choices depends on: i) how much temperature, oxygen, and flow vary at microspatial scales in streams and ii) the ability of insects to exploit that variation. We measured microspatial variation in temperature, oxygen saturation, and flow velocity within riffles of two streams in Montana, USA. Additionally, we examined the preferences of nymphs of the stoneflyPteronarcys californicato gradients of temperature, oxygen, and flow in lab choice experiments. Temperature and oxygen level varied modestly within stream riffles (∼ 1.8 °C, ∼ 8.0% of air saturation, respectively). By contrast, flow velocity was highly heterogeneous, often varying by more than 125 cm s-1within riffles and 44 cm s-1around individual cobbles. Exploiting micro-variation in flow may thus be the most reliable option for altering rates of oxygen transport. In alignment with this prediction,P. californicanymphs showed relatively little ability to exploit laboratory gradients in temperature and oxygen. By contrast, they readily exploited micro-variation in flow – consistently choosing higher flows when conditions were warm or hypoxic. These behaviors may help stream insects mitigate low-oxygen stress from climate change and other anthropogenic disturbances.

Summary Statement

Stonefly nymphs stressed by higher temperatures and lower oxygen availability often relocate to areas of higher flow. This behavior likely increases the ratio of oxygen supply to demand.
Long-term prognosis of adults with moderate-severe SARS-CoV-2 lower respiratory tract infection managed in primary care: prospective cohort study
Authors: Platteel T.N. , Koelmans J.C. , Cianci D. , Broers N.J.H. , de Bont E.G.P.M. , Cals J.W.L. , Venekamp R.P. , Verheij T.J.M.
Published: June 2022

Objectives

To determine differences in health-related quality of life (HRQoL) and presence and duration of symptoms between adults with and without established SARS-CoV-2 moderately severe lower respiratory tract infection (LRTI) in the 12 months following their primary care visit.

Design

Prospective cohort study

Setting

35 general practices in the provinces Noord-Brabant and Utrecht, the Netherlands.

Participants

Individuals aged ≥18 years who presented to their general practitioner (GP) with a moderately severe LRTI during the first COVID-19 waive in The Netherlands (March-June 2021) underwent serology testing (participants, GPs and study personnel remained blinded for serology outcomes during study conduct) and completed baseline and follow-up questionnaires. Of the 315 participants who gave consent, 277 (88%) were suitable for inclusion in the analyses. Complete follow-up date was available in 97% of participants.

Main outcome measures

1) Scores of SF-36; physical component summary (PCS), mental component summary (MCS) and subscales. 2) Risk of any and individual persisting symptoms (of cough, dyspnea, chest pain, fatigue, brain fog, headache, and anosmia/ageusia) over time.

Results

The change in SF-36 PSC (p=0.13), MCS (p=0.30), as well as subscale scores, over time did not differ between SARS-CoV-2 serology positive and negative participants after adjusting for sex, age, BMI, diabetes and chronic pulmonary conditions. The risk of any persisting symptom over time did not significantly differ between the groups (aHR 0.61, 95% CI 0.33-1.15), nor did the risk of individual symptoms.

Conclusions

In the 12 months following their moderately severe LRTI, primary care patients with and without confirmed SARS-CoV-2 infection had a comparable HRQoL profile. Albeit a considerable proportion of patients reported persistent symptoms, there was no evidence of a difference in the course of symptoms over time between patients with and without confirmed SARS-CoV-2 infection.

Trial registration

Dutch Trial Register (NTR) number NL8729
Safety of the fourth COVID-19 BNT162b2 mRNA (second booster) vaccine
Authors: Yechezkel Matan , Mofaz Merav , Patalon Tal , Gazit Sivan , Shmueli Erez , Yamin Dan
Published: June 2022

COVID-19 remains a global concern due to vaccine protection waning and the emergence of immuneevasive variants. While the effectiveness of a second booster vaccine dose (i.e., fourth inoculation) is well proven, its safety has yet to be fully understood, and vaccine compliance remains low. We conducted a prospective observational study to compare the short-term effects of the first and second BNT162b2 mRNA COVID-19 vaccine booster doses. 2,019 participants received smartwatches and filled in a daily questionnaire on systemic reactions to the vaccine. We found substantial changes from baseline levels in the 72 hours post-vaccination with the second booster in both self-reported and physiological reactions measured by the smartwatches. However, no significant difference in reactions was observed between the first and second boosters. We also found that participants who experienced more severe reactions to the first booster tended to likewise experience more severe reactions to the second booster. Our work supports the safety of the second booster from both subjective (self-reported questionnaires) and objective (physiological measurements) perspectives.
Survival intravascular photoacoustic imaging of lipid-rich plaque in cholesterol fed rabbits
Authors: Zhang Yi , Taylor Erik , Huang Nasi , Hamilton James , Cheng Ji-Xin
Published: June 2022

Intravascular photoacoustic (IVPA) imaging is a promising modality for quantitative assessment of lipid-laden atherosclerotic plaques. Yet, survival IVPA imaging of the same plaque in the same animal is not demonstrated. Here, using a sheathed IVUS/PA catheter of 0.9 mm in diameter, we demonstrate MRI-guided survival IVPA imaging of same plaque in an aorta of a well-established rabbit model mimicking atherosclerosis in human patients. The IVUS/PA results were confirmed by histology. These advances open the opportunity to evaluate the effectiveness of a therapy that aims to reduce the size of atherosclerotic plaques and demonstrates the potential of translating the IVPA catheter into clinic for detection of vulnerable plaques that are at high risk for thrombosis.
prolfqua: A Comprehensive R-package for Proteomics Differential Expression Analysis
Authors: Wolski Witold E. , Nanni Paolo , Grossmann Jonas , d’Errico Maria , Schlapbach Ralph , Panse Christian
Published: June 2022

Mass spectrometry is widely used for quantitative proteomics studies, relative protein quantification, and differential expression analysis of proteins. Nevertheless, there is a need for a flexible and easy-to-use application programming interface in R that transparently supports a variety of well principled statistical procedures. The prolfqua package can model simple experimental designs with a single explanatory variable and complex experiments with multiple factors and hypothesis testing. It integrates essential steps of the mass spectrometry-based differential expression analysis workflow: quality control, data normalization, protein aggregation, statistical modeling, hypothesis testing, and sample size estimation. The application programmer interface strives to be clear, predictable, discoverable, and consistent to make proteomics data analysis easy and exciting. Furthermore, the package implements benchmark functionality that can help to compare data acquisition, data preprocessing, or data modeling methods using a gold standard dataset. Finally, we show that the implemented methods allow sensitive and specific differential expression analysis. The prolfqua R package is available on GitHub https://github.com/fgcz/prolfqua, distributed under the MIT licence, and runs on all platforms supported by the R free software environment for statistical computing and graphics.
Genomic expression responses in sensu stricto Saccharomyces yeast to DNA damage induced by methyl methanesulfonate
Authors: Ramachandran Vignesh , Hatlestad Gregory , White Travis
Published: June 2022

Background

One way single-celled eukaryotes respond to DNA damage stress is by modifying their gene expression, facilitating genomic repair. Gene expression responses to DNA damage induced by methyl methanesulfonate (MMS) have been studied in the model organism Saccharomyces cerevisiae. However, lacking are investigations of the MMS stress responses in evolutionarily-related sensu stricto Saccharomyces species, including Saccharomyces cerevisiae.

Methods

Next-generation Illumina RNA-sequencing was to characterize the entire transcriptomes of four evolutionarily-related species of yeast, S. cerevisiae, S. paradoxus, S. mikatae, and S. bayanus, under control and experimental (MMS) conditions. Subsequent genomic studies included gene set enrichment analysis, promoter analysis, and concentration gradient studies.

Results

S. mikitae and S. paradoxus grew well in light of MMS while S. bayanus showed no growth. While there was fair overlap in induced and repressed genes, overall each species had unique expression responses. S. paradoxus and S. bayanus showed the most distinct changes with the former greatly inhibiting a large segment of its genome while the latter induced such segments. Gene set enrichment analysis revealed significantly modulated biologic, cellular, and molecular processes in each species. Promoter analysis revealed sets of induced/repressed transcription factors for genes highly modulated in the stress response. Concentration gradient studies of S. cerevisiae showed linear increase in gene expression of RAD54, DIN7, and IRC19 in response to increasing concentrations of MMS.

Conclusion

Overall, we depict the transcriptome changes of four evolutionarily-related sensu stricto yeast species and several functional genomic analyses to provide a novel understanding of their responses to MMS.
Regulation of protein translation by TRIM21
Authors: Li Huiyi , Liu Shun , Feng Qing , Deng Rilin , Wang Jingjing , Wang Xintao , Tian Renyun , Xu Yan , Chen Shengwen , Liu Qian , Wang Luoling , Li Xinran , Wan Mengyu , Peng Yousong , Tang Songqing , Xue Binbin , Zhu Haizhen
Published: June 2022

Abstract

Regulation of translation initiation is essential for maintenance of protein homeostasis and typically involves the phosphorylation of translation initiation factor eIF2α in eukaryotes. In response to stressors, cells employ eIF2α-dependent signaling to control translation initiation, which regulates multiple biological and physiological processes. However, the precise regulatory mechanism remains unclear. In this study, we focus on the role of TRIM21 in the regulation of protein translation mediated by protein kinase R (PKR), one of the classic kinases that phosphorylates eIF2α. TRIM21 deficiency enhances the activation of PKR under different types of stress. TRIM21 interacts with PKR, and the E3 ligase activity of TRIM21 is crucial for stress-triggered PKR inactivation. TRIM21 interacts with the PKR phosphatase PP1α and promotes K6-linked polyubiquitination of PP1α under stresses. Ubiquitination of PP1α augments its interaction with PKR, causing PKR inactivation and subsequent dephosphorylation of eIF2α, initiating protein synthesis. Moreover, TRIM21 constitutively restricts viral infection by reversing PKR-mediated inhibition of the protein synthesis of intrinsic antiviral genes. The TRIM21-PP1α axis acts as a newly discovered program that regulates PKR-associated protein synthesis and broadens our knowledge of antiviral genes. Moreover, TRIM21-mediated regulation of PKR activation provides evidence that TRIM21 may anticipate the interferon-dependent immunotherapy. Our study highlights the essential role of TRIM21 in regulating protein translation and may provide a novel target for the treatment of translation-associated diseases.
Speech decoding from a small set of spatially segregated minimally invasive intracranial EEG electrodes with a compact and interpretable neural network
Authors: Petrosyan Artur , Voskoboinikov Alexey , Sukhinin Dmitrii , Makarova Anna , Skalnaya Anastasia , Arkhipova Nastasia , Sinkin Mikhail , Ossadtchi Alexei
Published: June 2022

Abstract

Background

Speech decoding, one of the most intriguing BCI applications, opens up plentiful opportunities from rehabilitation of patients to direct and seamless communication between human species. Typical solutions rely on invasive recordings with a large number of distributed electrodes implanted through craniotomy. Here we explored the possibility of creating speech prosthesis in a minimally invasive setting with a small number of spatially segregated intracranial electrodes.

Methods

We collected one hour of data (from two sessions) in two patients implanted with invasive electrodes. We then used only the contacts that pertained to a single sEEG shaft or an ECoG stripe to decode neural activity into 26 words and one silence class. We employed a compact convolutional network-based architecture whose spatial and temporal filter weights allow for a physiologically plausible interpretation.

Results

We achieved on average 55% accuracy using only 6 channels of data recorded with a single minimally invasive sEEG electrode in the first patient and 70% accuracy using only 8 channels of data recorded for a single ECoG strip in the second patient in classifying 26+1 overtly pronounced words. Our compact architecture did not require the use of pre-engineered features, learned fast and resulted in a stable, interpretable and physiologically meaningful decision rule successfully operating over a contiguous dataset collected during a different time interval than that used for training. Spatial characteristics of the pivotal neuronal populations corroborate with active and passive speech mapping results and exhibit the inverse space-frequency relationship characteristic of neural activity. Compared to other architectures our compact solution performed on par or better than those recently featured in neural speech decoding literature.

Conclusions

We showcase the possibility of building a speech prosthesis with a small number of electrodes and based on a compact feature engineering free decoder derived from a small amount of training data.
Temporal distribution of cetaceans south of Pico Island (Azores, Portugal) - data obtained during whale-watching 2020
Authors: Zahn Peter , Kulike Lynn , Bloechl Armin
Published: June 2022

Land- and boat-based surveys were conducted to collect data during whale watching excursions in July/August and October 2020. Occurrence and distribution of cetaceans south of Pico Island (Azores) were determined. Ten species were sighted, 63 schools of Delphinids and 96 individuals of large whales. The most frequently sighted species were: Sperm whale (Physeter macrocephalus), Sei whale (Balaenoptera borealis), Atlantic spotted dolphin (Stenella frontalis), Common bottlenose dolphin (Tursiops truncatus), and Risso’s dolphin (Grampus griseus). An unusual high numbers of sightings of Sei whale in August and especially in October was noticed, and is not mentioned in the literature so far.
The conditional defector strategies can violate the most crucial supporting mechanisms of cooperation
Authors: Ibrahim Ahmed M.
Published: June 2022

Cooperation is essential for all domains of life. Ironically, it is intrinsically vulnerable to exploitation by cheats. Hence, there is an explanatory necessity that triggers a lot of evolutionary biologists to search for mechanisms that could support cooperation. In general, cooperation can emerge and be maintained when cooperators are sufficiently interacting with themself to provide a kind of assortment and reciprocity. One of the most crucial and common mechanisms to achieve that task are kin selection, spatial structure, and enforcement (punishment). Here I used agent-based simulation models to investigate these pivotal mechanisms against conditional defector strategies and concluded it could easily violate all of them and take over the population. This surprising outcome may cue us to rethink the evolution of cooperation as it illustrates that maintaining cooperation may be more difficult than previously thought. Moreover, besides the theoretical findings, there are empirical applications such as invading the cooperator population of pathogens by genetically engineered conditional defectors, which could be a potential therapy for many incurable diseases.
Mesopredator-mediated trophic cascade can break persistent phytoplankton blooms in coastal waters
Authors: Berthold Maximilian , Schumann Rhena , Reiff Volker , Wulff Rita , Schubert Hendrik
Published: June 2022

Managing eutrophied systems only bottom-up (nutrient decreases) can be economically and ecologically challenging. Top-down controls (consumption) were sometimes found to effectively control phytoplankton blooms. However, mechanistic insights, especially on possible trophic cascades, are less understood in brackish, species-poor coastal waters, where large cladocera are absent. In this study, we set-up large mesocosms for three consecutive years during growth season. One set of mesocosms was controlled by mesopredator (gobies and shrimp), whereas the other mesocosms had no such mesopredator present. The results were standardized to monitoring data of the ecosystem to denote possible differences between treatments and the system. We found that mesopredator mesocosms showed lower turbidity, phytoplankton biomass, and nutrients compared to no-mesopredator mesocosms and the ecosystem. This decrease allowed macrophytes to colonize water depths only sparsely colonized in the ecosystem. Rotifer biomass increased in mesopredator mesocosms compared to the ecosystem and no-mesopredator mesocosms. Likewise, copepod biomass that potentially grazes upon rotifers and other microzooplankton decreased in mesopredator mesocosms. No-mesopredator mesocosms were colonized by an omnivorous mesograzer (Gammarus tigrinus), potentially creating additional pressure on macrophytes and increasing grazing-mediated nutrient release. Zooplankton was not able to control the non-nutrient limited phytoplankton. We propose a new mechanism, where a higher mesopredator density will increase grazing on phytoplankton by promoting microzooplankton capable of grazing on picophytoplankton. This proposed mechanism would contrast with freshwater systems, where a decrease of zooplanktivorous fish would promote larger phytoplankton grazer like cladocera. Biomanipulation in such species-poor eutrophic coastal waters may be more successful, due to less trophic pathways that can cause complex top-down controls. Stocking eutrophic coastal waters with gobies and shrimps may be an alternative biomanipulative approach rather than selectively remove large piscivorous or omnivorous fish from eutrophic coastal waters.
The effects of data quantity on performance of temporal response function analyses of natural speech processing
Authors: Mesik Juraj , Wojtczak Magdalena
Published: June 2022

In recent years, temporal response function (TRF) analyses of non-invasive recordings of neural activity evoked by continuous naturalistic stimuli have become increasingly popular for characterizing response properties within the auditory hierarchy. However, despite this rise in TRF usage, relatively few educational resources for these tools exist. Here we use a dual-talker continuous speech paradigm to demonstrate how a key parameter of experimental design, the quantity of acquired data, influences TRF analyses fit to either individual data (subject-specific analyses), or group data (generic analyses). We show that although model performance monotonically increases with data quantity, the amount of data required to achieve significant prediction accuracies can vary substantially based on whether the fitted model contains densely (e.g., acoustic envelope) or sparsely (e.g., lexical surprisal) spaced features, especially when the goal of the analyses is to capture the aspect of neural responses uniquely explained by specific features. Moreover, we demonstrate that generic models can exhibit high performance on small amounts of test data (2-8 min), if they are trained on a sufficiently large data set. As such, they may be particularly useful for clinical and multi-task study designs with limited recording time. Finally, we show that the regularization procedure used in fitting TRF models can interact with the quantity of data used to fit the models, with larger training quantities resulting in systematically larger TRF amplitudes. Together, demonstrations in this work should aid the learning process of new users of TRF analyses, and in combination with other tools, such as piloting and power analyses, may serve as a detailed reference for choosing acquisition duration in future studies.
A novel cuproptosis-related long non-coding RNAs model that effectively predicts prognosis in hepatocellular carcinoma
Authors: Huang Enmin , Ma Ning , Ma Tao , Zhou Junyi , Yang Weisheng , Liu Chuangxiong , Hou Zehui , Chen Shuang , Zong Zhen , Zeng Bing , Li Yingru , Zhou Taicheng
Published: June 2022

Background

Cuproptosis has recently been considered a novel form of programmed cell death. To date, factors crucial to the regulation of this process remain unelucidated. Here, we aimed to identify long-chain non-coding RNAs (lncRNAs) associated with cuproptosis in order to predict the prognosis of patients with hepatocellular carcinoma (HCC).

Methods

Using RNA sequence data from The Cancer Genome Atlas Live Hepatocellular Carcinoma (TCGA-LIHC), a co-expression network of cuproptosis-related mRNAs and lncRNAs was constructed. For HCC prognosis, we developed a cuproptosis-related lncRNA signature (CupRLSig) using univariate Cox, lasso, and multivariate Cox regression analyses. Kaplan-Meier analysis was used to compare overall survival among high- and low-risk groups stratified by median CupRLSig score. Furthermore, comparisons of functional annotation, immune infiltration, somatic mutation, TMB (tumor mutation burden), and pharmacologic options were made between high- and low-risk groups.

Results

Our prognostic risk model was constructed using the cuproptosis-related PICSAR, FOXD2-AS1, and AP001065.1 lncRNAs. The CupRLSig high-risk group was associated with poor overall survival (hazard ratio = 1.162, 95% CI = 1.063– 1.270; p < 0.001). Model accuracy was further supported by receiver operating characteristic and principal component analysis as well as internal validation cohorts. A prognostic nomogram developed considering CupRLSig data and a number of clinical characteristics were found to exhibit adequate performance in survival risk stratification. Mutation analysis revealed that high-risk combinations with high TMB carried worse prognoses. Finally, differences in immune checkpoint expression and responses to chemotherapy as well as in targeted therapy among CupRLSig stratified high- and low-risk groups were explored.

Conclusions

The lncRNA signature constructed in this study is valuable in prognostic estimation in the setting of HCC.
Climate-induced range shifts drive adaptive response via spatio-temporal sorting of alleles
Authors: Luqman Hirzi , Wegmann Daniel , Fior Simone , Widmer Alex
Published: June 2022

Quaternary climate fluctuations drove many species to shift their geographic ranges, in turn shaping their genetic structures. Recently, it has been argued that adaptation may have accompanied species range shifts via the “sieving” of genotypes during colonisation and establishment. However, this has not been directly demonstrated, and knowledge remains limited on how different evolutionary forces, that are typically investigated separately, interacted to jointly mediate species responses to past climatic change. Here, through whole-genome resequencing of over 1200 individuals of the carnation Dianthus sylvestris coupled with integrated population genomic and gene-environment models, we reconstruct the past neutral and adaptive landscape of this species as it was shaped by the Quaternary glacial cycles. We show that adaptive responses emerged concomitantly with the post-glacial range shifts and expansions of this species in the last 20 thousand years. This was due to the spatial sorting of adaptive alleles through time, as populations expanded out of restrictive glacial refugia into the broader and more heterogeneous range of habitats available in the present-day inter-glacial. Our results reveal a tightly-linked interplay of migration and adaptation under past climate-induced range shifts that has acted to shape the spatial patterns of adaptive genetic variation we see in the species today.
Socioeconomic Resources are Associated with Distributed Alterations of the Brain’s Intrinsic Functional Architecture in Youth
Authors: Sripada Chandra , Gard Arianna , Angstadt Mike , Taxali Aman , Greathouse Tristan , McCurry Katherine , Hyde Luke W. , Weigard Alexander , Walczyk Peter , Heitzeg Mary
Published: June 2022

Little is known about how exposure to limited socioeconomic resources (SER) in childhood gets “under the skin” to shape brain development, especially using rigorous whole-brain multivariate methods in large, adequately powered samples. The present study examined resting state functional connectivity patterns from 5,821 youth in the Adolescent Brain Cognitive Development (ABCD) study, employing multivariate methods across three levels: whole-brain, network-wise, and connection-wise. Across all three levels, SER was associated with widespread alterations across the connectome. However, critically, we found that parental education was the primary driver of neural associations of SER. These parental education associations were robust to additional tests for confounding by head motion, and they exhibited notable concentrations in somatosensory and subcortical regions. Moreover, parental education associations with the developing connectome were partially accounted for by home enrichment activities, child’s cognitive abilities, and child’s grades, indicating interwoven links between parental education, child stimulation, and child cognitive performance. These results add a new data-driven, multivariate perspective on links between household SER and the child’s developing functional connectome.