bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous Reconstruction of Mandibular and Maxillary Defects Using the Single Free Fibular Osseocutaneous Flap
Authors: Lin Chih-Hung , Kudva Adarsh
Published: February 2021

Background

The facial profile requires adequate maxillary and mandibular projection. Although oral cancer tumor ablation might create ipsilateral maxillary and mandibular defect, fibular flap is popular in mandibular defect reconstruction. However, the maxillary defect results in sunken cheek or oral contracture. A single fibular flap can provide several struts to rebuild 2 jaws with adequate 3-dimensional spatial placement.

Materials and Methods

In total, 7 cases of secondary oral contracture and 2 cases of primary oncologic tumor ablation underwent single fibular flap for 2 jaws. Using multiple osteotomies, the distal fibular struts were used for the upper jaw, the second struts were discarded (3–4 cm), and proximal struts were used for mandible defect reconstruction. There were 5 accompanying free flaps for facial lining (2) and contralateral oral contracture release (3).

Results

All flaps survived without distal strut avascular necrosis, but 2 patients died from tumor metastasis. These patients presented adequate middle and lower facial profile. One patient underwent mandibular fibula strut distraction osteogenesis followed by integrated teeth on both jaws.

Conclusions

Single fibular transfer can accomplish 2 jaw bony defects and facial profile reconstruction. It can release oral contracture functionally and correct sunken cheek aesthetically. The reconstructed fibula can allow secondary teeth implantation rehabilitation.
Broad-Spectrum Antibiotics for Breast Expander/Implant Infection
Authors: Ozturk Cemile Nurdan , Ozturk Can , Sigurdson S. Lynn , Magner William J. , Sheedy Brenda , Lohman Robert , Moon Wong
Published: February 2021

Background

Despite best practices, infection remains the most common complication after breast reconstruction with expanders and implants, ranging from 2% to 29%. Empiric broad-spectrum antibiotics are frequently used in nonsurgical treatment of implant-associated infections in an effort to salvage the reconstruction. Pitfalls of antibiotherapy include adverse events, vascular access site complications, and drug resistance. Our goals were to describe management of implant infections with broad-spectrum antibiotics, review treatment related adverse events, and report on outcomes of therapy.

Patients and Methods

A retrospective review was carried out to identify patients who were treated with intravenous (IV) antibiotics for periprosthetic infection. Patient characteristics, surgical details, and antibiotic therapy–related adverse events were collected. Eventual outcome related to expander/implant salvage was noted.

Results

A total of 101 patients (111 treatment episodes) were identified. Mean duration of antibiotic treatment was 18 days (range, 1–40 days). The most commonly used parenteral treatment was a combination of daptomycin with piperacillin-tazobactam (65%) or an alternative agent (16%). Fifty-nine percent of treatment episodes resulted in salvage of the expander or implant. Thirty-five percent treatment episodes were associated with 1 or more adverse events: diarrhea (12.6%), rash (10%), vaginal candidiasis (3.6%), agranulocytosis/neutropenic fever (3.6%), nausea (3.6%), urinary complaint (0.9%), myositis (0.9%), headache (0.9%), vascular line occlusion (1.8%), deep vein thrombosis (1.8%), and finger numbness (0.9%). No patients developed Clostridium difficile colitis. Five episodes (4%) needed discontinuation of antibiotics because of severe adverse events. The prosthesis was explanted in 3 of the cases of discontinued treatment.

Conclusions

Our findings show favorable outcomes and well-tolerated adverse effects with broad-spectrum parenteral antibiotherapy for periprosthetic infection. However, every effort should be made to deescalate therapy by narrowing the spectrum or limiting the duration, to minimize adverse events and development of bacterial resistance. Treating surgeons need to carefully weigh benefits of therapy and be aware of potential complications that might necessitate discontinuation of treatment.
Intracranial Volume Measured and Correlated to Cephalic Index in Syndromic and Nonsyndromic Anterior Brachycephaly
Authors: Kronig Otto D.M. , Kronig Sophia A.J. , Van Adrichem Léon N.A.
Published: February 2021

Background

Premature fusion of both coronal sutures (anterior brachycephaly) alters skull shape and potentially affects intracranial volume (ICV). Currently little is known about preoperative ICV in anterior brachycephaly. Aim is to measure preoperative ICV and compare this with normative data. Additionally, ICV will be correlated to most used clinical method of quantification: cephalic index (CI).

Methods

Preoperative patients with anterior brachycephaly (age, ≤12 months) were included and categorized by syndrome (when present). Computed tomography scans were used for ICV measurement by manual segmentation (OsiriX (Fondation OsiriX, Geneva, Switzerland)). Intracranial volume of each subgroup was compared with Lichtenberg normative cranial volume growth curves for controls. Cephalic index was calculated and correlated to ICV using Pearson correlation coefficient.

Results

Thirty-four patients with both syndromic and nonsyndromic anterior brachycephaly were included: 17 with Apert syndrome, 6 with Muenke syndrome, 5 with Saethre Chotzen syndrome, 3 with Crouzon, 1 with craniofrontonasal dysplasia, and 2 nonsyndromal. Mean age at preoperative computed tomography scan was 4 months (1–10 months). Mean ICV was 847.31 cm3 (473.91–1459.22 cm3). Nineteen of 34 patients had skull volumes between ±2 SD curves of Lichtenberg, none of the patients had an ICV smaller than −2 SD and 15 of 34 had an ICV larger than +2 SD. Mean ICV in Apert syndrome was 829.85 cm3 (473.91–1061.53 cm3), in Muenke syndrome 942.06 cm3 (768.02–1136.75 cm3), in Saethre Chotzen syndrome 779.72 cm3 (609.21–1002.95 cm3), in Crouzon syndrome 700.57 cm3 (652.31–784.32 cm3), in craniofrontonasal dysplasia 738.97 cm3, and in the nonsyndromal group 1154.64 cm3 (850.07–1459.22 cm3). Apert had a mean greater than +2SD above the mean, the other subgroups had a mean within normal ranges (±2 SD). Correlation between severity of brachycephaly and overall ICV was low (r = 0.42).

Conclusions

Mean preoperative ICV in both syndromic and nonsyndromic anterior brachycephaly was 847.31 cm3. Intracranial volume in anterior brachycephaly is in 55.9% between normal ranges (±2 SD). In 44.1% ICV was greater than +2 SD, especially in Apert syndrome (11/16 Apert patients). None of the included patients had a deviant small ICV of less than −2 SD. Additionally, low correlation between ICV and CI (r = 0.42) was found and therefore CI is not suitable for estimating ICV in anterior brachycephaly.
Globalization of The Journal of Craniofacial Surgery Over The Last Decade: A Continent, Country, and State Level Analysis
Authors: Liechty Andrew E. , O’Rorke Erin V. , French Mackenzie M. , Vu Giap H. , Robinson Emily M. , Cho Daniel Y. , Friedrich Jeffrey B. , Susarla Srinvas M.
Published: February 2021

Craniofacial surgery continues to be a rapidly evolving field, due in part to interdisciplinary collaboration that has allowed for sharing of knowledge and methodologies, which has expanded greatly due to online journals and publications. The Journal of Craniofacial Surgery (JCS) is a highly regarded journal that has attracted attention for its mission to increase diversity and global representation in manuscript submissions and research publications. The purpose of this study is to provide an objective measurement of global participation in craniofacial research specifically as it pertains to the JCS. Through a bibliometric analysis, the country of origin of all articles published in the JCS from 2010 to 2019 was analyzed. In line with its mission, the JCS increased its overall production 1.9 times during the past decade and increased its global representation 1.6 times, as represented by the number of countries contributing (78). The journal produced 8147 articles with Turkey (1424), USA (1397), China (1178), South Korea (1023), and Italy (644) being the top producers. The highest represented states were Florida (156), New York (130), California (117), Massachusetts (112), and Pennsylvania (106). The Journal of Craniofacial Surgery has the greatest diversity of country representation of the major plastic and reconstructive journals compared. Overall the JCS has stayed true to its mission to foster craniofacial research and is a valuable resource for craniofacial surgeons across the world. This study provides an analysis of trends in global contributions to craniofacial research and highlights areas for further increasing global contributors to the field of craniofacial surgery.
Neurodevelopmental, Cognitive, and Psychosocial Outcomes for Individuals With Pathogenic Variants in the TCF12 Gene and Associated Craniosynostosis
Authors: Kennedy-Williams Patrick , Care Helen , Dalton Louise , Horton Jo , Kearney Anna , Rooney Natasha , Hotton Matthew , Pinckston Molly , Huggons Esme , Culshaw Laura , Kilcoyne Sarah , Johnson David , Wilkie Andrew O.M. , Wall Steven
Published: February 2021

Heterozygous mutations in the TCF12 gene were discovered in 2013 as a cause of craniosynostosis (CS). However, limited information regarding the behavioral phenotypic profile is available. Here the authors provide the first detailed study of the neurodevelopmental, cognitive, and psychosocial outcomes for patients with a pathogenic TCF12 variant and associated CS.

A clinical casenote audit was conducted at the 4 UK highly specialized craniofacial centers. A total of 35 patients aged 18 months to 10 years with an identified TCF12 pathogenic variant and CS (bicoronal CS = 45.7%, unicoronal CS = 40.0%, multisuture = 14.3%) were included. Standardized screening and/or assessment of full-scale intelligence quotient, social communication, development, behavior, and self-concept were conducted.

In the majority of cases, outcomes were consistent with age-related expectations. About 75% of patients demonstrated no delay across any early developmental domain, while 84.6% demonstrated full-scale intelligence quotient scores within 1 standard deviation of the population mean. Significant behavioral difficulties were demonstrated by parent reporters in 26.3% to 42.1% of cases (dependent upon domain). Clinically elevated social communication profiles were present in (41.7%) of parent-reported cases. Levels of self-concept (at age 10) were consistent with age-related normative data.

Most patients with a TCF12 pathogenic variant had a mild behavioral and cognitive phenotype, although they may be at a slightly increased risk of social communication difficulties and psychosocial issues. Although not measured statistically, there were no clear associations between surgical history and cognitive, behavioral, or psychosocial outcomes. This paper highlights the need for robust integrated developmental assessment of all CS patients, particularly those with an identified syndrome.
Prognostic Accuracy of VqSOFA for Predicting 28-day Mortality in Patients with Suspected Sepsis in the Emergency Department
Authors: Suttapanit Karn , Wisan Munlika , Sanguanwit Pitsucha , Prachanukool Thidathit
Published: February 2021

Background:

Sepsis screening in the emergency department (ED) is challenging. The quick Sequential Organ Failure Assessment (qSOFA) score had poor accuracy for predicting mortality in both the intensive care unit and ED. High lactate levels were associated with an increased mortality. However, a previous study using lactate levels in combination with the qSOFA score did not observe a meaningful improvement in predictive accuracy. This study assessed the prognostic accuracy of venous lactate levels plus the qSOFA (VqSOFA) score for predicting 28-day mortality.

Methods:

Patients who visited the Ramathibodi ED with suspected sepsis were enrolled. The VqSOFA, qSOFA, and Sequential Organ Failure Assessment (SOFA) scores were calculated using the initial vital signs and laboratory values. Prognostic accuracy was measured using the area under the receiver operating characteristic (AUROC) curve of the VqSOFA score and Sepsis-3 criteria for predicting 28-day mortality.

Results:

In total, 1,139 patients were enrolled, 118 of whom died within 28 days of admission. The AUROCs of the VqSOFA, qSOFA, and SOFA scores were 0.851 (95% CI 0.813–0.889), 0.813 (95% CI 0.772–0.854), and 0.728 (95% CI 0.671–0.784), respectively. Using VqSOFA score ≥ 3 as the cutoff, the sensitivity, specificity, and positive likelihood ratio were 74.6%, 82.5%, and 4.25%, respectively. VqSOFA ≥ 3 was linked to a low probability of 28-day survival and higher odds of vasopressor and ventilator use within 24 h.

Conclusions:

VqSOFA was more predictive of 28-day mortality and vasopressor and mechanical ventilator use than the qSOFA and SOFA scores.
An Intention-to-treat View of Lung Transplantation for Interstitial Lung Disease: Successful Strategies to Minimize Waiting List and Posttransplant Mortality
Authors: Zhu Michael Z.L. , Levvey Bronwyn J. , McGiffin David C. , Snell Gregory I.
Published: February 2021

Background.

Access to lung transplantation (LTx) and rates of waiting list and posttransplant mortality for patients with interstitial lung disease (ILD) remain problematic. We evaluated the outcomes of ILD patients listed for LTx at our institution.

Methods.

Between 2012 and 2018, adult patients with ILD were listed and transplanted from a donor-pool that included extended criteria and donation after circulatory-determined death donors. Patients were categorized as experiencing 1 of 4 competing events: transplant, waitlist death, delisting, or alive on waitlist. Multivariable competing risk regression analysis was performed to determine predictors of waitlist death/delisting. Posttransplant survival was analyzed using Kaplan-Meier methods.

Results.

Among 187 patients listed, 82% (153 of 187) underwent LTx (median time-to-transplant, 2.0 mo), whereas 16% (30 of 187) died or were delisted (median time-to-event, 1.6 mo). At 90 d, 6 mo, and 12 mo after listing, 51%, 63%, and 78% of patients had been transplanted, whereas 10%, 14%, and 16% had died or were delisted. Multivariable predictors of waitlist death/delisting were: blood group O compared to A (subdistribution hazard ratio [SHR]: 6.43, P < 0.001), shorter height (per 1 cm, SHR: 1.11, P < 0.001), hospitalization at listing (SHR: 3.98, P = 0.002), and reduced 6-min-walk test distance (per 50 m, SHR: 1.28, P = 0.001). Among LTx recipients, 24% (36 of 153) underwent single LTx. Donor lungs were 58% (88 of 153) extended-criteria, inclusive of 24% (37 of 153) circulatory-determined death. Ninety-day and 1-, 3-, and 5-y retransplant free survival were 97% ± 1%, 92% ± 2%, 81% ± 4%, and 69% ± 6%.

Conclusions.

Patients with ILD require a rapid transit to LTx after listing. Despite this, the vast majority of ILD patients in this study reached LTx with excellent early and midterm outcomes.
Cost Structures of US Organ Procurement Organizations
Authors: Held Philip J. , Bragg-Gresham Jennifer L. , Peters Thomas G. , McCormick Frank , Chertow Glenn , Vaughan William P. , Roberts John P.
Published: February 2021

Background.

The goal is to provide a national analysis of organ procurement organization (OPO) costs.

Methods.

Five years of data, for 51 of the 58 OPOs (2013–2017, a near census) were obtained under a FOIA. OPOs are not-for-profit federal contractors with a geographic monopoly. A generalized 15-factor cost regression model was estimated with adjustments to precision of estimates (P) for repeated observations. Selected measures were validated by comparison to IRS forms.

Results.

Decease donor organ procurement is a $1B/y operation with over 26 000 transplants/y. Over 60% of the cost of an organ is overhead. Profits are $2.3M/OPO/y. Total assets are $45M/OPO and growing at 9%/y. “Tissue” (skin, bones) generates $2–3M profit/OPO/y. A comparison of the highest with the lower costing OPOs showed our model explained 75% of the cost difference. Comparing costs across OPOs showed that highest-cost OPOs are smaller, import 44% more kidneys, face 6% higher labor costs, report 98% higher compensation for support personnel, spend 46% more on professional education, have 44% fewer assets, compensate their Executive Director 36% less, and have a lower procurement performance (SDRR) score.

Conclusions.

Profits and assets suggest that OPOs are fiscally secure and OPO finances are not a source of the organ shortage. Asset accumulation ($45M/OPO) of incumbents suggests establishing a competitive market with new entrants is unlikely. Kidney-cost allocations support tissue procurements. Professional education spending does not reduce procurement costs. OPO importing of organs from other OPOs is a complex issue possibly increasing cost ($6K/kidney).
Sandarakinorhabdus rubra sp. nov., and Sandarakinorhabdus oryzae sp. nov., isolated from oxidized rice paddy soil
Authors: Cho Geon-Yeong , Whang Kyung-Sook
Published: February 2021

Three Gram-stain-negative, motile or non-motile, rod-shaped, facultatively aerobic strains, designated MO-4T, NP-34 and NM-18T, were isolated from oxidized rice paddy soil in Chungbuk, Republic of Korea. Colonies were circular and convex with entire margins, red in colour on R2A after 3 days at 30 °C. The three strains grew at pH 5.0–10.0 (optimum, pH 8.0), at 15–45 °C (optimum, 30 °C) and at salinities of 0–1.5 % (w/v) NaCl (optimum, 0.4 % NaCl). The results of phylogenetic analyses based on 16S rRNA gene sequences indicated that the three isolates represent members of the genus

Sandarakinorhabdus

and strains MO-4T and NP-34 were most closely related to

Sandarakinorhabdus cyanobacteriorum

TH057T (97.7 %) and

Sandarakinorhabdus limnophila

DSM 17366T (97.1 %). NM-18T showed highest 16S rRNA gene sequence similarities to

Sandarakinorhabdus limnophila

DSM 17366T (98.7 %) and

Sandarakinorhabdus cyanobacteriorum

TH057T (96.7 %). Genomic similarities between strains MO-4T and NM-18T and the two type strains of species of the genus

Sandarakinorhabdus

based on average nucleotide identity and digital DNA–DNA hybridization values were lower than the species delineation thresholds. The major fatty acids were iso-C18 : 1 ω7c and summed feature 3. The DNA G+C contents of strains MO-4T and NM-18T, obtained from genome sequencing data, were 67.6 and 66.6 mol%, respectively. On the basis of these genotypic and phenotypic characteristics, the three strains are assigned to two novel species of the genus

Sandarakinorhabdus

, for which the names Sandarakinorhabdus rubra sp. nov. (type strain MO-4T =KACC 21378=NBRC 114106) and Sandarakinorhabdus oryzae sp. nov. (type strain NM-18T=KACC 21379=NBRC 113957) are proposed.
Comparison of the clinical characteristics and mortality in ARDS due to COVID-19 versus ARDS due to Influenza A-H1N1pdm09
Authors: Hernández Cárdenas Carmen , Lugo Gustavo , Hernández García Diana , Pérez-Padilla Rogelio
Published: February 2021

Importance

Infection with the SARS-Cov-2 and Influenza A-H1N1 viruses is responsible for the first pandemics of the 21st century. Both of these viruses can cause severe pneumonia and acute respiratory distress syndrome (ARDS). The clinical differences and mortality associated with these two pandemic pneumonias in patients with ARDS are not well established

Objective

To compare case-fatality between ARDS-Covid-19 and ARDS-Influenza A (H1N1), adjusting for known prognostic risk factors.

Design, Setting and Participants

One hundred forty-seven patients with COVID-19 were compared with 94 with Influenza A-H1N1, all of these were admitted to the intensive care unit of the Referral Center for Respiratory Diseases and COVID-19 in Mexico City and fulfilled the criteria of ARDS.

Results

Patients arrived at the hospital after 9 days of symptoms. Influenza patients had more obesity, more use of Norepinephrine, and higher levels of lactic dehydrogenase and glucose, and fewer platelets and lower PaO2/FIO2. Crude mortality was higher in COVID than in influenza (39% vs. 22%; p = 0.005). In a Cox proportional hazard model, patients with a diagnosis of COVID-19 had a hazard ratio (HR) = 3.7; 95% Confidence Interval [CI] = 1.9-7.4, adjusted for age, gender, sequential organ failure assessment (SOFA) score, ventilatory ratio, and prone ventilation. In the fully adjusted model, the ventilatory ratio and the absence of prone-position ventilation were also predictors of mortality.

CONCLUSION

COVID-19 patients treated in an intensive care unit (ICU) had a 3.7 times higher risk of death than similar patients with Influenza A-H1N1, after adjusting for SOFA score and other relevant risk factors for mortality.

Question

Is the mortality of ARDS associated with Covid-19 greater than that of ARDS associated to influenza H1N1?

Findings

In a Cox proportional hazard model, patients with a diagnosis of COVID-19 had a hazard ratio (HR) = 3.7; 95% Confidence Interval [CI] = 1.9-7.4, adjusted for age, gender, sequential organ failure assessment (SOFA) score.

Meaning

COVID-19 patients treated in an intensive care unit (ICU) had a 3.7 times higher risk of death than similar patients with Influenza A-H1N1
Ultrafast Simulation of Large-Scale Neocortical Microcircuitry with Biophysically Realistic Neurons
Authors: Oláh Viktor János , Pedersen Nigel P , Rowan Matthew JM
Published: February 2021

Understanding the activity of the mammalian brain requires an integrative knowledge of circuits at distinct scales, ranging from ion channel gating to circuit connectomics. To understand how multiple parameters contribute synergistically to circuit behavior, neuronal computational models are regularly employed. However, traditional models containing anatomically and biophysically realistic neurons are computationally demanding even when scaled to model local circuits. To overcome this limitation, we trained several artificial neural net (ANN) architectures to model the activity of realistic, multicompartmental neurons. We identified a single ANN that accurately predicted both subthreshold and action potential firing and correctly generalized its responses to previously unobserved synaptic input. When scaled, processing times were orders of magnitude faster compared with traditional approaches, allowing for rapid parameter-space mapping in a circuit model of Rett syndrome. Thus, we present a novel ANN approach that allows for rapid, detailed network experiments using inexpensive, readily available computational resources.
Sense of absence: Spatial perception through active sensing by insect antennal mechanosensory system
Authors: Ifere Nwuneke Okereke , Shidara Hisashi , Sato Nodoka , Ogawa Hiroto
Published: February 2021

Animals perceive their surroundings by using various modalities of sensory inputs to navigate their locomotion. Nocturnal insects such as crickets use mechanosensory inputs mediated by their antennae to navigate under dark conditions. Active sensing with voluntary antennal movements improves spatial information, but it remains unclear how accurately the insects can perceive the surrounding space by using their antennal system. Crickets exhibit escape behavior in response to a short air-puff, which is detected by the abdominal mechanosensory organ called cerci and is perceived as a “predator approach” signal. We placed objects of different shapes at different locations with which the cricket actively made contact using its antenna. We then examined the effects on wind-elicited escape. The crickets changed their movement trajectory depending on the shape and location of the objects so that they could avoid collision with these obstacles even when the escape behavior was triggered by another modality of stimulus. For instance, when a wall was placed in front of the crickets so that it was detected by one side of their antenna, the escape trajectory in response to a stimulus from behind was significantly biased toward the side opposite the wall. However, if the antenna on the free side without the wall was ablated, this modulation to avoid collision diminished, suggesting that the antenna on the free side provided information of “absence” of obstacles. This study demonstrated that crickets were able to perceive spatial information, including the presence or absence of objects by active sensing with their antennal system.

Summary Statement

Crickets can acquire spatial information such as shape, location and orientation of objects through active sensing by antennal mechanosensory system, which also provides information about the absence of objects.
Automated strain separation in low-complexity metagenomes using long reads
Authors: Vicedomini R. , Quince C. , Darling A. E. , Chikhi R.
Published: February 2021

High-throughput short-read metagenomics has enabled large-scale species-level analysis and functional characterization of microbial communities. Microbiomes often contain multiple strains of the same species, and different strains have been shown to have important differences in their functional roles. Despite this, strain-level resolution from metagenomic sequencing remains challenging. Recent advances on long-read based methods enabled accurate assembly of bacterial genomes from complex microbiomes and an as-yet-unrealized opportunity to resolve strains. Here we present Strainberry, a metagenome assembly method that performs strain separation in single-sample low-complexity metagenomes and that relies uniquely on long-read data. We benchmarked Strainberry on mock communities and showed it consistently produces strain-resolved assemblies with near-complete reference coverage and 99.9% base accuracy. We also applied Strainberry on real datasets for which it improved assemblies generating 20-118% additional genomic material than conventional metagenome assemblies on individual strain genomes. Our results hence demonstrate that strain separation is possible in low-complexity microbiomes using a single regular long read dataset. We show that Strainberry is also able to refine microbial diversity in a complex microbiome, with complete separation of strain genomes. We anticipate this work to be a starting point for further methodological improvements aiming to provide better strain-resolved metagenome assemblies in environments of higher complexities.
Power spectra reveal distinct BOLD resting‐state time courses in white matter
Authors: Li Muwei , Gao Yurui , Ding Zhaohua , Gore John C.
Published: February 2021

Accurate characterization of the time courses of BOLD signal changes is crucial for the analysis and interpretation of functional MRI data. While several studies have shown that white matter (WM) exhibits distinct BOLD responses evoked by tasks, there have been no comprehensive investigations into the time courses of spontaneous signal fluctuations in WM. We measured the power spectra of the resting‐state time courses in a set of regions within WM identified as showing synchronous signals using independent components analysis. In each component, a clear separation between voxels into two categories was evident, based on their power spectra: one group exhibited a single peak, the other had an additional peak at a higher frequency. Their groupings are location‐specific, and their distributions reflect unique neurovascular and anatomical configurations. Importantly, the two categories of voxels differed in their engagement in functional integration, revealed by differences in the number of inter‐ regional connections based on the two categories separately. Moreover, the power spectral measurements in voxels with two peaks in specific components predict specific human behaviors. Taken together, these findings suggest WM signals are heterogeneous in nature and depend on local structural‐vascular‐functional associations.
Human blood lipoprotein predictions from1H NMR spectra: protocol, model performances and cage of covariance
Authors: Khakimov Bekzod , Hoefsloot Huub C.J. , Mobaraki Nabiollah , Aru Violetta , Kristensen Mette , Lind Mads V. , Holm Lars , Castro-Mejía Josué L , Nielsen Dennis S , Jacobs Doris M. , Smilde Age K. , Engelsen Søren Balling
Published: February 2021

Lipoprotein subfractions are biomarkers for early diagnosis of cardiovascular diseases. The reference method, ultracentrifugation, for measuring lipoproteins is time consuming and there is a need to develop a rapid method for cohort screenings. Here we present partial least squares regression models developed using1H-NMR spectra and concentrations of lipoproteins as measured by ultracentrifugation on 316 healthy Danes. Different regions of the1H-NMR spectra representing signals of the lipoproteins and different lipid species were investigated to develop parsimonious, reliable and best performing prediction models. 65 LP main and subfractions were predictable with an accuracy Q2of > 0.6 on test set samples. The models were tested on an independent cohort of 290 healthy Swedes with predicted and reference values matching by up to 85-95%. The software was developed to predict lipoproteins in human blood using1H-NMR spectra and made freely available to be applied for future cohort screenings.
Perception of biological motion in point-light displays by jumping spiders
Authors: De Agrò Massimo , Rößler Daniela C. , Kim Kris , Shamble Paul S.
Published: February 2021

Over the last 50 years, point-light displays have been successfully used to explore how animals respond to dynamic visual stimuli—specifically, differentiation of the biological from the non-biological. These stimuli are designed to preserve movement patterns while minimizing static detail, with single dots representing each of the main joints of a moving animal. Imposed by their internal skeleton, vertebrate movements follow a specific semi-rigid dynamic pattern, termed “biological-motion”, which can be used to distinguish animate from inanimate objects. Although biological motion detection has not been studied in invertebrates, rigid exoskeletons force many species to also follow semi-rigid movement principles. Due to their highly developed visual system and complex visual behaviors, we investigated the capability of jumping spiders to discriminate biological from non-biological motion using point-light display stimuli. By constraining spiders so that they could rotate but not move directionally, we simultaneously presented two point-light display stimuli with specific dynamic traits and registered their preference by observing which pattern they turned towards. Jumping spiders clearly demonstrated the ability to discriminate between stimuli. However, spiders showed no preference when both stimuli presented patterns with semi-rigid movements, results that are directly comparable to responses in vertebrate systems. This represents the first demonstration of biological motion recognition in an invertebrate, posing crucial questions about the evolutionary history of this ability and complex visual processing in non-vertebrate systems.
Cryo-EM study on the homo-oligomeric ring formation of yeast TRiC/CCT subunits reveals TRiC ring assembly mechanism
Authors: Liu Caixuan , Wang Huping , Jin Mingliang , Han Wenyu , Wang Shutian , Wang Yanxing , Wang Fangfang , Su Chun , Hong Xiaoyu , Zhao Qiaoyu , Cong Yao
Published: February 2021

The complex eukaryotic chaperonin TRiC/CCT helps maintain cellular protein homeostasis, however, its assembly mechanism remains largely unknown. To address the subunit specificity in TRiC assembly, we express each of the individual yeast TRiC subunit inE. coli. Our cryo-EM structural study and biochemical analyses demonstrate that CCT1/2/6 can form TRiC-like homo-oligomeric double ring (HR) complex, however ATP-hydrolysis cannot trigger their ring closure; after deletion of the long N-terminal extension, CCT5 can form the closed double-ring structure; while CCT3/4/7/8 cannot form the HRs. It appears that CCT1 forms a HR in a unique spiral configuration, and ATP-hydrolysis can drive it to re-assemble with an inserted extra subunit-pair. Our data suggest that CCT5 could be the leading subunit in ATP-hydrolysis-driven TRiC ring closure. Moreover, we demonstrate that ADP is sufficient to trigger the assembly of the HRs and TRiC from the assembly intermediate micro-complex form. Our study reveals that through evolution, the more ancestral subunits may have evolved to take more responsibilities in TRiC ring assembly, and we propose a possible assembly mechanism of TRiC involving subunit-pair insertion. Collectively, our study gives hints on the structural basis of subunit specificity in TRiC assembly and cooperativity, beneficial for future TRiC-related therapeutic strategy development.
REMY: A platform for the rapid interrogation of epigenome modifications on yeast
Authors: Waldman Alison C. , Rao Balaji M. , Keung Albert J.
Published: February 2021

Histone proteins are decorated with a combinatorially and numerically diverse set of biochemical modifications. Here we describe a versatile and scalable platform termedRapid interrogation ofEpigenomeModifications usingYeast surface display (REMY), which enables efficient characterization of histone modifications without the need for recombinant protein production. As proof-of-concept, we first used REMY to rapidly profile the histone H3 and H4 residue writing specificities of the human histone acetyltransferase, p300. Subsequently, we used REMY to screen a large panel of commercially available anti-acetylation antibodies for their specificities, identifying many suitable and unsuitable reagents. Further, use of REMY enabled efficient mapping of the large binary crosstalk space between acetylated residues on histones H3 and H4, and uncovered previously unreported residue interdependencies affecting p300 activity. Our results show that REMY is a useful tool that can advance our understanding of chromatin biology by enabling efficient interrogation of the complexity of epigenome modifications.
The mitochondrial pyruvate carrier (MPC) complex is one of three pyruvate-supplying pathways that sustain Arabidopsis respiratory metabolism
Authors: Le Xuyen H. , Lee Chun-Pong , Millar A. Harvey
Published: February 2021

Malate oxidation by plant mitochondria enables the generation of both oxaloacetate (OAA) and pyruvate for tricarboxylic acid (TCA) cycle function, potentially eliminating the need for pyruvate transport into mitochondria in plants. Here we show that the absence of the mitochondrial pyruvate carrier 1 (MPC1) causes the co-commitment loss of its orthologs, MPC3/MPC4, and eliminates pyruvate transport into Arabidopsis mitochondria, proving it is essential for MPC complex function. While the loss of either MPC or mitochondrial pyruvate-generating NAD-malic enzyme (NAD-ME) did not cause vegetative phenotypes, the lack of both reduced plant growth and caused an increase in cellular pyruvate levels, indicating a block in respiratory metabolism, and elevated the levels of branched-chain amino acids at night, a sign of alterative substrate provision for respiration.13C-pyruvate feeding of leaves lacking MPC showed metabolic homeostasis were largely maintained except for alanine and glutamate, indicating that transamination contributes to restoration of the metabolic network to an operating equilibrium by delivering pyruvate independently of MPC into the matrix. Inhibition of alanine aminotransferases (AlaAT) when MPC1 is absent resulted in extremely retarded phenotypes in Arabidopsis, suggesting all pyruvate-supplying enzymes work synergistically to support the TCA cycle for sustained plant growth.
Urea nitrogen recycling via gut symbionts increases in hibernators over the winter fast
Authors: Regan Matthew D. , Chiang Edna , Liu Yunxi , Tonelli Marco , Verdoorn Kristen M. , Gugel Sadie R. , Suen Garret , Carey Hannah V. , Assadi-Porter Fariba M.
Published: February 2021

Hibernation is a mammalian strategy that uses metabolic plasticity to reduce energy demands and enable long-term fasting. Fasting mitigates winter food scarcity but eliminates dietary nitrogen, jeopardizing body protein balance. Here, we reveal gut microbiome-mediated urea nitrogen recycling in hibernating 13-lined ground squirrels (TLGS). Ureolytic gut microbes incorporate urea nitrogen into organic compounds that are absorbed by the host, with the nitrogen reincorporated into the TLGS protein pool. Urea nitrogen recycling is greatest after prolonged fasting in late winter, when urea transporter abundance in gut tissue and urease gene abundance in the microbiome are highest. These results reveal a functional role for the gut microbiome in hibernation and suggest mechanisms by which urea nitrogen recycling contributes to protein balance in other monogastric animals, including humans.

One Sentence Summary

Ground squirrels and their gut symbionts benefit from urea nitrogen recycling throughout hibernation.
Evaluating the reliability of human brain white matter tractometry
Authors: Kruper John , Yeatman Jason D. , Richie-Halford Adam , Bloom David , Grotheer Mareike , Caffarra Sendy , Kiar Gregory , Karipidis Iliana I. , Roy Ethan , Chandio Bramsh Q. , Garyfalldis Eleftherios , Rokem Ariel
Published: February 2021

The validity of research results depends on the reliability of analysis methods. In recent years, there have been concerns about the validity of research that uses diffusion-weighted MRI (dMRI) to understand human brain white matter connectionsin vivo, in part based on reliability of the analysis methods used in this field. We defined and assessed three dimensions of reliability in dMRI-based tractometry, an analysis technique that assesses the physical properties of white matter pathways: (1) reproducibility, (2) test-retest reliability and (3) robustness. To facilitate reproducibility, we provide software that automates tractometry (https://yeatmanlab.github.io/pyAFQ). In measurements from the Human Connectome Project, as well as clinical-grade measurements, we find that tractometry has high test-retest reliability that is comparable to most standardized clinical assessment tools. We find that tractometry is also robust: showing high reliability with different choices of analysis algorithms. Taken together, our results suggest that tractometry is a reliable approach to analysis of white matter connections. The overall approach taken here both demonstrates the specific trustworthiness of tractometry analysis and outlines what researchers can do to demonstrate the reliability of computational analysis pipelines in neuroimaging.
Condensation of theDrosophilaNerve Cord is Oscillatory and depends on Coordinated Mechanical Interactions
Authors: Karkali Katerina , Tiwari Prabhat , Singh Anand , Tlili Sham , Jorba Ignasi , Navajas Daniel , Muñoz José J. , Saunders Timothy E. , Martin-Blanco Enrique
Published: February 2021

During development, organs must form with precise shapes and sizes. Organ morphology is not always obtained through growth; a classic counterexample is condensation of the nervous system duringDrosophilaembryogenesis. The mechanics underlying such condensation remain poorly understood. Here, we combinein totolive-imaging, biophysical and genetic perturbations, and atomic force microscopy to characterize the condensation of theDrosophilaventral nerve cord (VNC) during embryonic development at both subcellular and tissue scales. This analysis reveals that condensation is not a unidirectional continuous process, but instead occurs through oscillatory contractions alternating from anterior and posterior ends. The VNC mechanical properties spatially and temporally vary during its condensation, and forces along its longitudinal axis are spatially heterogeneous, with larger ones exerted between neuromeres. We demonstrate that the process of VNC condensation is dependent on the coordinated mechanical activities of neurons and glia. Finally, we show that these outcomes are consistent with a viscoelastic model of condensation, which incorporates time delays due to the different time scales on which the mechanical processes act, and effective frictional interactions. In summary, we have defined the complex and progressive mechanics driving VNC condensation, providing insights into how a highly viscous tissue can autonomously change shape and size.
Biased removal and loading of centromeric histone H3 during reproduction underlies uniparental genome elimination
Authors: Marimuthu Mohan P.A. , Maruthachalam Ravi , Bondada Ramesh , Kuppu Sundaram , Tan Ek-Han , Britt Anne , Chan Simon S.W. , Comai Luca
Published: February 2021

Uniparental genome elimination is a dramatic case of centromeric failure, resulting in the postzygotic loss of a parental chromosome set. Genome partitioning during cell division relies on centromere attachment to spindle fibers through kinetochores. Centromeres are epigenetically specified by CENP-A (CENH3), a conserved centromeric specific histone H3 variant. In Arabidopsis, CENH3 modification results in haploid inducers, whose genome is eliminated frequently when crossed to the wild type. To investigate the underlying mechanism, we dissected the timing and molecular features of genome elimination. In zygotes and early embryos from genome elimination crosses, CENH3 occupied only the centromeres contributed by the wild-type parent. Haploid inducer chromosomes had defective kinetochores and missegregated, often forming micronuclei. This uniparental loss of centromere identity is initiated by the removal of altered CENH3 at fertilization, while wild-type CENH3 persists and maintains strong centromeric identity. Weak centromeres were capable of rebuilding functional kinetochores, but often failed when in competition with normal ones. We induced a similar weak state by mitotic dilution of wild-type CENH3. Furthermore, weakness was suppressed by crosses of haploid inducers to other variants of haploid inducers, and enhanced by mutations inVIM1, a ubiquitin ligase known to modify CENH3 and centromeric DNA methylation.. The differential stability of altered CENH3 during reproduction has important genetic and evolutionary implications.
NADPH Oxidase 2 Derived Reactive Oxygen Species Promote CD8+T cell Effector Function
Authors: Chen Jing , Liu Chao , Chernatynskaya Anna V. , Newby Brittney , Brusko Todd M. , Xu Yuan , Morgan Nadine , Santarlas Christopher P. , Reeves Westley H. , Tse Hubert M. , Leiding Jennifer W. , Mathews Clayton E.
Published: February 2021

Oxidants participate in lymphocyte activation and function. We previously demonstrated that eliminating the activity of NADPH oxidase 2 (NOX2) significantly impaired the effectiveness of autoreactive CD8+cytotoxic T lymphocytes (CTL). However, the molecular mechanisms impacting CTL function remain unknown. Here, we studied the role of NOX2 in both non-obese diabetic (NOD) mouse and human CTL function. Genetic ablation or chemical inhibition of NOX2 in CTL significantly suppressed activation-induced expression of the transcription factor T-bet, the master transcription factor of the Tc1 cell lineage, and T-bet target effectors genes such as IFNγ and granzyme B. Inhibition of NOX2 in both human and mouse CTL prevented target cell lysis. We identified that superoxide generated by NOX2 must be converted into hydrogen peroxide to transduce the redox signal in CTL. Further, we show that NOX2-generated oxidants deactivate the Tumor Suppressor Complex leading to mTOR complex 1 activation and CTL effector function. These results indicate that NOX2 plays a non-redundant role in T cell receptor-mediated CTL effector function.
Dynamics of anteroposterior axis establishment in a mammalian embryo-like system
Authors: Anlaş Kerim , Gritti Nicola , Oriola David , Arató Krisztina , Nakaki Fumio , Lim Jia Le , Sharpe James , Trivedi Vikas
Published: February 2021

1.

In the mammalian embryo, specification of the anteroposterior (AP) axis demarcates one of the first steps of body plan formation. While this process requires interactions with extra-embryonic tissues in the native embryo, minimalin vitrosystems from embryonic stem cells (ESCs) undergo initial AP polarization in the absence of any localized, external cues. This self-organizing potential of stem cells remains not well understood. Here, we study such an initial symmetry breaking event in gastruloids, an establishedin vitromodel for mammalian body plan formation, using the mesodermal marker gene Brachyury or T (Bra/T) to denote the onset of AP axis specification and concomitant germ layer formation. Through aggregate fusion experiments and manipulation of initial culture conditions as well as key developmental signalling pathways, we probe the dynamics of Bra/T polarization. We further conduct single-cell (sc) RNA sequencing of gastruloids at early stages to identify incipient molecular signatures of germ layer commitment and differences between Bra/T+and Bra/T−populations during as well as after symmetry breaking. Moreover, we transcriptionally compare early development of gastruloids to the mouse embryo and conclude that gastruloids reproducibly undergo AP axis and germ layer specification in a parallel, but distinct manner: While their primed pluripotent cell populations adopt a more mesenchymal state in lieu of an epithelial epiblast-like transcriptome, the emerging mesendodermal lineagesin vitroare nevertheless similar to their in vivo equivalents. Altogether, this study provides a comprehensive analysis of self-organized body plan establishment in a minimalin vitrosystem of early mammalian patterning and highlights the regulative capacity of mESCs, thereby shedding light on underlying principles of axial polarity formation.
Decoding the brain state-dependent relationship between pupil dynamics and resting state fMRI signal fluctuation
Authors: Sobczak Filip , Pais-Roldán Patricia , Takahashi Kengo , Yu Xin
Published: February 2021

Pupil dynamics serve as a physiological indicator of cognitive processes and arousal states of the brain across a diverse range of behavioral experiments. Pupil diameter changes reflect brain state fluctuations driven by neuromodulatory systems. Resting state fMRI (rs-fMRI) has been used to identify global patterns of neuronal correlation with pupil diameter changes, however, the linkage between distinct brain state-dependent activation patterns of neuromodulatory nuclei with pupil dynamics remains to be explored. Here, we identified four clusters of trials with unique activity patterns related to pupil diameter changes in anesthetized rat brains. Going beyond the typical rs-fMRI correlation analysis with pupil dynamics, we decomposed spatiotemporal patterns of rs-fMRI with principal components analysis (PCA) and characterized the cluster-specific pupil-fMRI relationships by optimizing the PCA component weighting via decoding methods. This work shows that pupil dynamics are tightly coupled with different neuromodulatory centers in different trials, presenting a novel PCA-based decoding method to study the brain state-dependent pupil-fMRI relationship.