bluuebunny/crossref_metadata_2025 huggingface dataset:
Search for fast radio transients using Arecibo drift-scan observations at 1.4 GHz
Authors: Perera B B P , Smith A J , Vaddi S , Carballo-Rubio R , McGilvray A , Venkataraman A , Roshi D Anish , Manoharan P K , Perillat P , Lieb E , Lorimer D R , McLaughlin M A , Agarwal D , Aggarwal K , Ransom S M
Published: October 2021

We conducted a drift-scan observation campaign using the 305-m Arecibo telescope in 2020 January and March when the observatory was temporarily closed during the intense earthquakes and the initial outbreak of the COVID-19 pandemic, respectively. The primary objective of the survey was to search for fast radio transients, including fast radio bursts (FRBs) and rotating radio transients (RRATs). We used the seven-beam ALFA receiver to observe different sections of the sky within the declination region ∼(10°–20°) on 23 nights and collected 160 h of data in total. We searched our data for single-pulse transients, of covering up to a maximum dispersion measure of 11 000 pc cm−3 at which the dispersion delay across the entire bandwidth is equal to the 13-s transit length of our observations. The analysis produced more than 18 million candidates. Machine learning techniques sorted the radio frequency interference and possibly astrophysical candidates, allowing us to visually inspect and confirm the candidate transients. We found no evidence for new astrophysical transients in our data. We also searched for emission from repeated transient signals, but found no evidence for such sources. We detected single pulses from two known pulsars in our observations and their measured flux densities are consistent with the expected values. Based on our observations and sensitivity, we estimated the upper limit for the FRB rate to be <2.8 × 105 sky−1 d−1 above a fluence of 0.16 Jy ms at 1.4 GHz, which is consistent with the rates from other telescopes and surveys.
Not all peaks are created equal: the early growth of supermassive black holes
Authors: Ni Yueying , Di Matteo Tiziana , Feng Yu
Published: October 2021

In this work, we use the constrained Gaussian realization technique to study the early growth of supermassive black holes (SMBHs) in cosmological hydrodynamic simulations, exploring its relationship with features of the initial density peaks on large scales, ∼ 1 h−1Mpc. Our constrained simulations of volume (20 h−1Mpc)3 successfully reconstruct the large-scale structure as well as the black hole growth for the hosts of the rare 109 M⊙ SMBHs found in the bluetides simulation at z ∼ 7. We run a set of simulations with constrained initial conditions by imposing a $5 \sigma _0(R_\mathrm{G})$ peak on the scale of $\\ R_\mathrm{ G} = 1$ h−1Mpc varying different peak features, such as the shape and compactness as well as the tidal field surrounding the peak. We find that initial density peaks with high compactness and low tidal field induce the most rapid BH growth at early epochs. This is because compact density peaks with a more spherical large-scale matter distribution lead to the formation of the highest gas inflows (mostly radial) in the centres of haloes which boost the early BH accretion. Moreover, such initially compact density peaks in low tidal field regions also lead to a more compact BH host galaxy morphology. Our findings can help explain the tight correlation between BH growth and host galaxy compactness seen in observations.
Membrane nanodomains modulate formin condensation for actin remodeling in Arabidopsis innate immune responses
Authors: Ma Zhiming , Sun Yanbiao , Zhu Xinlu , Yang Liang , Chen Xu , Miao Yansong
Published: October 2021

The assembly of macromolecules on the plasma membrane concentrates cell surface biomolecules into nanometer- to micrometer-scale clusters (nano- or microdomains) that help the cell initiate or respond to signals. In plant–microbe interactions, the actin cytoskeleton undergoes rapid remodeling during pathogen-associated molecular pattern-triggered immunity (PTI). The nanoclustering of formin-actin nucleator proteins at the cell surface has been identified as underlying actin nucleation during plant innate immune responses. Here, we show that the condensation of nanodomain constituents and the self-assembly of remorin proteins enables this mechanism of controlling formin condensation and activity during innate immunity in Arabidopsis thaliana. Through intrinsically disordered region-mediated remorin oligomerization and formin interaction, remorin gradually recruits and condenses formins upon PTI activation in lipid bilayers, consequently increasing actin nucleation in a time-dependent manner postinfection. Such nanodomain- and remorin-mediated regulation of plant surface biomolecules is expected to be a general feature of plant innate immune responses that creates spatially separated biochemical compartments and fine tunes membrane physicochemical properties for transduction of immune signals in the host.
Tranexamic Acid in Gastrointestinal Bleeding: A Systematic Review and Meta-Analysis
Authors: Dionne Joanna C. , Oczkowski Simon J. W. , Hunt Beverley J. , Antonelli Massimo , Wijnberge Marije , Raasveld Senta Jorinde , Vlaar Alexander P. J. ,   for ESICM Transfusion Taskforce and the GUIDE Group
Published: October 2021

OBJECTIVES:

Tranexamic acid is proposed as a treatment for gastrointestinal bleeding. The Haemorrhage Alleviation with Tranexamic Acid-Intestinal System trial evaluated extended-use (24 hr) high-dose tranexamic acid, prompting a reappraisal for tranexamic acid in gastrointestinal bleeding.

DATA SOURCES:

We conducted a systematic review and meta-analysis of randomized controlled trials comparing tranexamic acid with usual care or placebo in adults with gastrointestinal bleeding. We searched MEDLINE, EMBASE, and CENTRAL (inception to September 2019).

Data Selection:

Two reviewers independently screened citations, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool in duplicate. The main outcomes were mortality, bleeding, and adverse events.

DATA EXTRACTION:

Studies were analyzed as high-dose IV tranexamic acid versus all other dosing strategies for tranexamic acid using fixed-effects models. We assessed certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach.

DATA SYNTHESIS:

Five randomized controlled trials evaluated extended-use high-dose IV tranexamic acid, seven evaluating low-dose IV or enteral tranexamic acid. Extended-use high-dose IV tranexamic acid did not reduce mortality (relative risk, 0.98%; 95% CI, 0.88–1.09; I
2 = 63%; high certainty) or bleeding (relative risk, 0.92; 95% CI, 0.82–1.04; p = 0.17 and absolute risk differences, –0.7%; 95% CI, –1.5 to 0.3; high certainty) but resulted in a small increase in deep venous thrombosis (relative risk, 2.01; 95% CI, 1.08–3.72; I
2 = 0%), pulmonary embolism (relative risk, 1.78; 95% CI, 1.06–3.0; I
2 = 0%), and seizure (relative risk, 1.73; 95% CI, 1.03–2.93) with high certainty. Low-dose IV/enteral tranexamic acid did not reduce mortality (relative risk, 0.62; 95% CI, 0.36–1.09; I
2 = 0%) but did reduce risk of rebleeding (relative risk, 0.5; 95% CI, 0.33–0.75; I
2 = 9%) and need for surgery (relative risk, 0.58; 95% CI, 0.38–0.88; I
2 = 11%), with moderate certainty.

CONCLUSIONS:

Extended-use high-dose IV tranexamic acid does not improve mortality or bleeding outcomes and increases adverse events. Low-dose/enteral tranexamic acid may be effective in reducing hemorrhage; more evidence is required to demonstrate its safety.
Phalangeal and Metacarpal Fractures of the Hand: Preventing Stiffness
Authors: Neumeister Michael W. , Winters James N. , Maduakolum Erica
Published: October 2021

Fractures of the phalangeal or metacarpal bones of the hand are common. Many of these fractures are treated without surgery. However, both conservative and operative management of fractures of the hand can result in stiffness. Stiffness is the most common complication in the management of hand fractures. The key to preventing stiffness is early range of motion exercises. This article challenges many of the current treatment regimens offered to patients with the so-called unstable fractures. The evaluation of the patients’ function is the primary factor that should determine the course of conservation versus operative management. X-rays do not demonstrate function and therefore act as an adjunct only to the care of the patient. The goal of treating hand fractures is to restore function. Early motion may not only improve healing but may also hasten the return to normal hand function. The tenets of how to prevent stiffness are described in this review.
Paediatric nasal dermoid: evaluation and management
Authors: Adil Eelam , Rahbar Reza
Published: October 2021

Purpose of review

The aim of this study was to present the evaluation and current management of congenital paediatric nasal dermoid.

Recent findings

There has been a trend towards less invasive surgical excision techniques, including purely endoscopic excision, endoscopic-assisted approaches and midline excision with nasal bone osteotomies and bone flap. These approaches allow adequate access for both total resection and nasal contour and skull base reconstruction. Following resection, if nasal bone osteotomies are insufficient for restoring nasal appearance, free temporoparietal fascial graft and/or conchal cartilage can be considered. For nasal tip deformities, interdomal sutures and free fat grafting are a suitable option.

Complete surgical excision remains the treatment of choice for nasal dermoid lesions. The surgical approach taken and reconstruction depends on the type of lesion (cyst versus sinus or fistula), location (intranasal versus extranasal), whether or not there is intracranial extension, and experience of the surgical team.
A Prediction Model for Selective Use of Facial Computed Tomography in Blunt Head Trauma Patients
Authors: Huang Li-Kuo , Huang Chih-Sheng , Tu Hsi-Feng , Chiang Kuo-Hsien , Bajani Francesco , Fu Chih-Yuan
Published: October 2021

Background:

Head trauma patients may have concomitant facial fractures, which are usually underdetected by head computed tomography alone. This study aimed to identify the clinical indicators of facial fractures and to develop a risk-prediction model to guide the discriminative use of additional facial computed tomography in head trauma.

Methods:

The authors retrospectively reviewed head trauma patients undergoing simultaneous head and facial computed tomography at a Level II trauma center from 2015 to 2018. Multivariate logistic regression analysis was used to evaluate independent risk factors for concomitant facial fractures in head trauma patients using data collected from 2015 to 2017, and a risk-prediction model was created accordingly. Model performance was validated with data from 2018.

Results:

In total, 5045 blunt head trauma patients (development cohort, 3534 patients, 2015 to 2017; validation cohort, 1511 patients, 2018) were enrolled. Concomitant facial fractures occurred in 723 head trauma patients (14.3 percent). Ten clinical and head computed tomographic variables were identified as predictors, including age, male sex, falls from elevation, motorcycle collisions, Glasgow Coma Scale scores less than 14, epistaxis, tooth rupture, facial lesions, intracranial hemorrhage, and skull fracture. In the development cohort, the model showed good discrimination (area under the receiver operating characteristic curve = 0.891), calibration (Hosmer-Lemeshow C test, p = 0.691), and precision (Brier score = 0.066). In the validation cohort, the model demonstrated excellent discrimination (area under the receiver operating characteristic curve = 0.907), good calibration (Hosmer-Lemeshow C test, p = 0.652), and good precision (Brier score = 0.083). With this model, 77.1 percent of unnecessary facial computed tomography could be avoided.

Conclusion:

This model could guide the discriminative use of additional facial computed tomography to detect concomitant facial fractures in blunt head trauma.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Technical Refinement in Three-Dimensional Nipple-Areola Complex Tattooing of the Reconstructed Breast
Authors: Ruffolo Alexis M. , Bruce William J. , Daugherty Timothy H. F. , Lee Jason , Sommer Nicole Z.
Published: October 2021

Three-dimensional nipple-areola complex tattooing has previously been described as an alternative to surgical reconstruction using local flaps and grafts. This technique offers patients an option that can achieve aesthetically pleasing results without a donor site, changes in projection over time, or additional scarring. Plastic surgeons may be limited in their ability to create a realistic-appearing nipple-areola complex because of limited experience with basic tattooing techniques and unfamiliarity with the artistic principles of light and shadow required to create depth on a two-dimensional surface. Consistent results can be achieved with attention to the technical pearls discussed in this article.
Modern Fat Grafting Techniques to the Face and Neck
Authors: Azoury Saïd C. , Shakir Sameer , Bucky Louis P. , Percec Ivona
Published: October 2021

Learning Objectives:

After studying this article, the participant should be able to: 1. Understand age-related changes to the face and neck and pertinent anatomy and discuss important aspects of fat graft harvesting, processing, and infiltration. 2. Recognize key differences between common techniques for fat processing and infiltration and develop a plan for patients based on site-specific facial anatomical zones. 3. Appreciate the utility of fat grafting as an adjunct to other facial rejuvenating procedures such as face lift and blepharoplasty procedures and list the potential complications from fat grafting to the face and neck.

Fat grafting to the face and neck aids in volume restoration, thereby addressing soft-tissue atrophy associated with the aging face, acquired conditions, or congenital malformations. Often, fat grafting may sufficiently restore facial volume alone or in conjunction with other facial rejuvenation procedures. Facial/neck fat grafting requires a systematic and thoughtful approach, with special care to atraumatic technique. This CME article covers the principles and techniques for modern facial fat grafting to the face and neck. Increasing data support the ability of autologous fat to produce significant and sustainable appearance-related changes. The authors follow the general principles of the Coleman technique for facial fat grafting and have observed tremendous success over the years. Other techniques for facial fat grafting are also discussed including microfat and nanofat processing. As the understanding of facial fat compartments continues to evolve, the authors may better predict fat grafting outcomes following augmentation. Finally, the technique described as “lipotumescence” has been successfully used in the breast and other regions of the body that have radiation damage and is discussed in this article specifically for the face and neck.
Improving compliance of risk assessment and nonpharmacological interventions for deep venous thrombosis prevention in a respiratory ICU: a best practice implementation project
Authors: Wu Jinyan , Zhu Shunfang , Munn Zachary , Zhou Chunlan
Published: October 2021

Objectives:

To increase the compliance with deep venous thrombosis (DVT) nonpharmacologic prophylaxis best practice recommendations while ensuring appropriate and structured nonpharmacologic prophylaxis for patients in the respiratory ICU.

Background:

DVT is a major problem for patients, with those who are critically ill representing a high-risk population for developing the condition. Nonpharmacologic prophylaxis is considered an effective intervention. However, the application of such interventions in practice has not been optimal to date.

Methods:

The current project was conducted in a respiratory ICU of a tertiary hospital. Audit criteria were developed on the basis of an evidence summary developed by the Joanna Briggs Institute, whereby the institute's Practical Application of Clinical Evidence System program to facilitate an audit and feedback cycle was utilized as an implementation framework. Baseline and follow-up audits on nonpharmacological DVT prophylaxis were conducted for 35 patients against five evidence-based recommendations. In addition, the nurses’ knowledge and attitude regarding DVT prophylaxis were investigated both prior to and postimplementation.

Results:

In the baseline audit, compliance with the five evidence-based audit criteria was less than 15%. After the implementation of strategies including education, person-centered care, financial and human-resource support, there was a significant improvement in all the audit criteria. In addition, improvements in the nurses’ knowledge and attitude regarding DVT prophylaxis were reported. The rate of discharged patients due to a deterioration of their condition decreased from 31.4 to 5.7% in the follow-up cycle. One DVT patient occurred in the baseline data, whereas no new incidences of DVT were found in the follow-up data.

Conclusion:

The project not only improved nurses’ knowledge and attitude regarding DVT prevention, but also remarkably improved the implementation of nonpharmacological DVT prophylaxis. The application of evidence-based nonpharmacological DVT prophylaxis may improve patients’ outcomes in the ICU.
Central venous catheter insertion in adult patients: a best practice implementation project
Authors: Ferreira Juliana D.N. , dos Santos Kelli B. , Siqueira Eduardo C. , Gomes Edimar P. , Martini Larissa , Fraga João B.P. , Lima Maria Augusta M. , Poveda Vanessa B.
Published: October 2021

Introduction and aims:

The central venous catheter (CVC) is an indispensable device in the daily practice of modern medicine. Thus, the implementation of CVC interferes with the care of a large number of patients. This project aimed to implement the best practices in the insertion of CVC in adult hospitals in Brazil.

Methods:

The project had three phases, including forming a team and conducting the baseline audit; identifying problems and developing strategies; and conducting a follow-up audit to assess the impact on compliance with best practices. A baseline audit was conducted at a public Hospital in Minas Gerais, Brazil, in June and July 2019. For data collection, direct observation of the procedure was performed and through the PACES (Practical Application of Clinical Evidence System) audit and feedback tool to check the compliance criteria established in the literature. After implementation, a second audit was conducted in August 2019.

Results:

During the baseline audit, the absence of adequate compliance with the criteria for using an ultrasound to insert the catheter and correct hand hygiene before the procedure was identified. Theoretical–practical training was carried out, including the use of ultrasound to perform the procedure, using an adapted mannequin. The follow-up audit showed an improvement in the compliance rate for the following audit criteria: physical assessment before the procedure (92–100%); evaluation of the most suitable vein for insertion of the catheter, avoiding the femoral vein (92–100%); correct hand hygiene before the procedure (58–100%); maintenance of asepsis throughout the procedure (83–91%) and use of ultrasound to guide venous catheterization (17–100%).

Conclusion:

The current project proved that training the team can be effective in optimizing the implementation of evidence.
Training women's pelvic floor muscles during pregnancy and postpartum at primary health centers: a best practice implementation project
Authors: de Viñaspre Regina Ruiz , Garrido Ana Elena , Alvarez Maria Angeles
Published: October 2021

Introduction and aims:

Pelvic floor muscle training (PFMT) enhances muscle strength and coordination, and prevents urinary incontinence associated with giving birth. The goal was to improve women's PFMT during pregnancy and postpartum in La Rioja, Spain.

Methods:

This evidence implementation project used the JBI evidence implementation framework. First, we conducted the PFMT baseline audit: to assess the criteria for midwife training, we sent a questionnaire to all midwives. To measure the criteria for PFMT and urinary incontinence risk assessment, we reviewed the medical records of 60 women selected through consecutive sampling and 15 other women at risk of urinary tract infections (UTIs) for the inclusion criteria in a PFMT program. Second, we used the Getting Research into Practice guidelines to identify barriers to the fulfillment of each criterion and design and implement strategies to improve compliance. Finally, we repeated the audit to measure compliance and verify the changes.

Results:

The midwives received updated PFMT, optimizing compliance with the first criterion from 67 to 100%. The remaining criteria -- providing PFMT for pregnant women, identifying women at high risk of incontinence, and facilitating a supervised PFMT program for women at high risk of UTIs -- went from 0% compliance to 17, 96, and 67%, respectively.

Conclusion:

This project was effective in building consensus, improving midwives’ practice, and facilitating mothers’ PFMT. The project continued during the novel coronavirus [coronavirus disease 2019 (COVID-19)] epidemic in Spain as the midwives, women, and managers were involved in the change because of a well designed registration system and the use of online tools for communication between midwives and women.
Implementation and extended evaluation of the Euroimmun Anti-SARS-CoV-2 IgG assay and its contribution to the United Kingdom’s COVID-19 public health response
Authors: Otter Ashley David , Bown Abbie , D’Arcangelo Silvia , Bailey Daniel , Semper Amanda , Hewson Jacqueline , Catton Matthew , Perumal Prem , Sweed Angela , Jones Jessica , Harvala Heli , Lamikanra Abigail , Zambon Maria , Andrews Nick , Whitaker Heather , Linley Ezra , Mentzer Alexander J , Skelly Donal , Knight Julian C. , Klenerman Paul ,   PHE Porton Euroimmun testing group, Amirthalingam Gayatri , Taylor Stephen , Rowe Cathy , Vipond Richard , Brooks Tim
Published: October 2021

1.

In March 2020, the Rare and Imported Pathogens Laboratory at Public Health England, Porton Down, was tasked by the Department of Health and Social Care with setting up a national surveillance laboratory facility to study SARS-CoV-2 antibody responses and population-level sero-surveillance in response to the growing SARS-CoV-2 outbreak. In the following 12 months, the laboratory tested more than 160,000 samples, facilitating a wide range of research and informing PHE, DHSC and UK government policy. Here we describe the implementation and use of the Euroimmun anti-SARS-CoV-2 IgG assay and provide an extended evaluation of its performance. We present a markedly improved sensitivity of 91.39% (≥14 days 92.74%, ≥21 days 93.59%) compared to our small-scale early study, and a specificity of 98.56%. In addition, we detail extended characteristics of the Euroimmun assay: intra- and inter-assay precision, correlation to neutralisation and assay linearity.
Inefficient exploitation of accessory receptors reduces the sensitivity of chimeric antigen receptors
Authors: Burton Jake , Siller-Farfán Jesús A. , Pettmann Johannes , Salzer Benjamin , Kutuzov Mikhail , van der Merwe P. Anton , Dushek Omer
Published: October 2021

Chimeric antigen receptors (CARs) can re-direct T cells to target abnormal cells but their activity is limited by a profound defect in antigen sensitivity, the source of which remains unclear. Here we show that, while CARs have a >100-fold lower antigen sensitivity compared to the T cell receptor (TCR) when antigen is presented on antigen-presenting-cells (APCs), they have nearly identical sensitivity when antigen is presented as purified protein on artificial surfaces. We next measured the impact of engaging accessory receptors (CD2, LFA-1, CD28, CD27, 4-1BB) on antigen sensitivity by adding their purified ligands. Unexpectedly, we found that engaging CD2 or LFA-1 improved TCR antigen sensitivity by 125 and 22-fold, respectively, but only improved CAR sensitivity by <5-fold. This differential effect of CD2 and LFA-1 engagement on TCR versus CAR sensitivity was confirmed using APCs. We found that sensitivity to antigen can be partially restored by fusing the CAR variable domains to the TCR CD3ε subunit (also known as a TRuC), and fully restored by exchanging the CAR variable domains with the TCRαβ variable domains (also known as STAR or HIT). Importantly, these improvements in TRuC and STAR/HIT sensitivity can be predicted by their enhanced ability to exploit CD2 and LFA-1. These findings demonstrate that the CAR sensitivity defect is a result of their inefficient exploitation of accessory receptors, and suggest approaches to increase sensitivity.
Investigation of the futalosine pathway for menaquinone biosynthesis as a novel target in the inhibition of Chlamydia trachomatis infection
Authors: Dudiak Brianne M. , Nguyen Tri M. , Needham David , Outlaw Taylor C. , McCafferty Dewey G.
Published: October 2021

Chlamydia trachomatis, an obligate intracellular bacterium with limited metabolic capabilities, possesses the futalosine pathway for menaquinone biosynthesis. Futalosine pathway enzymes have promise as narrow spectrum targets, but the activity and essentiality of chlamydial menaquinone biosynthesis have yet to be established. In this work, menaquinone-7 (MK-7) was identified as a C. trachomatis-produced quinone through LC-MS/MS. An immunofluorescence-based assay revealed that treatment of C. trachomatis-infected HeLa cells with futalosine pathway inhibitor docosahexaenoic acid (DHA) reduced inclusion number, inclusion size, and infectious progeny. Supplementation with MK-7 nanoparticles rescued the effect of DHA on inclusion number, indicating that the futalosine pathway is a target of DHA in this system. These results open the door for menaquinone biosynthesis inhibitors to be pursued in antichlamydial development.
Total parenteral nutrition drives glucose metabolism disorders by modulating gut microbiota and its metabolites
Authors: Sun Haifeng , Wang Peng , Maitiabula Gulisudumu , Zhang Li , Yang Jianbo , Zhang Yupeng , Gao Xuejin , Li Jieshou , Xue Bin , Li Chao-Jun , Wang Xinying
Published: October 2021

The occurrence of glucose metabolism disorders is a potentially fatal complication of total parenteral nutrition (TPN). However, the mechanisms of TPN-associated glucose metabolism disorders remain unclarified. Given that the glucose metabolism was related to gut microbiome and TPN could induce the gut microbiota dysbiosis, we hypothesized that gut microbiota and its metabolites played the important roles in TPN-associated glucose metabolism disorders. By performing a cohort study of 256 type 2 IF patients given PN, we found that H-PN (PN>80%) patients exhibited insulin resistance and a higher risk of complications. Then, TPN and microbiome transfer mice model showed that TPN promoted glucose metabolism disorders by inducing gut microbiota dysbiosis; 16S rRNA sequencing demonstrated that the abundance of Lactobacillaceae was decreased in mice model and negatively correlated with HOMA-IR and lipopolysaccharide level in TPN patients. Untargeted metabolomics found that indole-3-acetic acid (IAA) was decreased in TPN mice, and the serum level was also decreased in H-PN patients. Furthermore, GLP-1 secretion regulated by IAA and aryl hydrocarbon receptor was reduced in TPN mice and patients; IAA or liraglutide completely prevented glucose metabolism disorders in TPN mice. In conclusion, TPN drives glucose metabolism disorders by inducing alteration of gut microbiota and its metabolites.
Social experience dependent plasticity of mouse song selectivity without that of song components
Authors: Agarwalla Swapna , Bandyopadhyay Sharba
Published: October 2021

Syllable sequences in male mouse ultrasonic-vocalizations (USVs), “songs”, contain structure -quantified through predictability, like birdsong and aspects of speech. Apparent USV innateness and lack of learnability, discount mouse USVs for modelling speech-like social communication and its deficits. Informative contextual natural sequences (SN) were theoretically extracted and they were preferred by female mice. Primary auditory cortex (A1) supragranular neurons show differential selectivity to the same syllables in SN and random sequences (SR). Excitatory neurons (EXNs) in females showed increases in selectivity to whole SNs over SRs based on extent of social exposure with male, but syllable selectivity remained unchanged. Thus mouse A1 single neurons adaptively represent entire order of acoustic units without altering selectivity of individual units, fundamental to speech perception. Additionally, observed plasticity was replicated with silencing of somatostatin positive neurons, which had plastic effects opposite to EXNs, thus pointing out possible pathways involved in perception of sound sequences.
Collaborative Federated Learning behind Hospitals’ Firewalls for Predicting Histological Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer
Authors: du Terrail Jean Ogier , Léopold Armand , Joly Clément , Beguier Constance , Andreux Mathieu , Maussion Charles , Schmauch Benoît , Tramel Eric W. , Bendjebbar Etienne , Zaslavskiy Mikhail , Wainrib Gilles , Milder Maud , Gervasoni Julie , Guérin Julien , Durand Thierry , Livartowski Alain , Moutet Kelvin , Gautier Clément , Djafar Inal , Moisson Anne-Laure , Marini Camille , Galtier Mathieu , Bataillon Guillaume , Heudel Pierre-Etienne
Published: October 2021

1

Triple-Negative Breast Cancer (TNBC) is a rare cancer, characterized by high metastatic potential and poor prognosis, and has limited treatment options compared to other breast cancers. The current standard of care in non-metastatic settings is neoadjuvant chemotherapy (NACT), with the goal of breast-conserving surgery and for an in vivo assessment of chemosensitivity. However, the efficacy of this treatment varies significantly across patients, and this histological response heterogeneity is still poorly understood partly due to the paucity of available curated TNBC data. Motivated by this problem, we investigate the use of machine learning (ML) to predict at diagnosis the histological response to NACT for early TNBC patients. To overcome the known biases of related small scale studies while respecting data privacy, we conduct, for the first time, a TNBC study in a multi-centric fashion behind hospitals’ firewalls using collaborative Federated Learning (FL). Thereby allowing access to enough TNBC data to sustain a complete response heterogeneity investigation. We show evidence that local ML models relying on Whole-Slide Images (WSIs) at diagnosis are able to predict the histological response to NACT as accurately as current clinical approaches, which rely on time-consuming expert annotations. We demonstrate that collaborative training further improves performance over single-center training outperforming clinical methods. Our ML model is interpretable by design, and we show that it is sensitive to specific histological patterns. While we identify known predictive biomarkers among them, this proof of concept for real-world collaborative FL paves the way for future biomarker discovery using unprecedently large datasets.
Evaluation of peripheral enhancement on contrast-enhanced CT and corresponding pathological findings in colorectal liver metastases after preoperative chemotherapy
Authors: Tamura Akio , Ishida Kazuyuki , Sone Misato , Yoshioka Kunihiro
Published: October 2021

Objective

To correlate peripheral enhancement on contrast-enhanced computed tomography (CE-CT) of post-chemotherapy colorectal liver metastases (CRLM) patients with the pathological findings.

Methods

Forty-four patients with CRLM who underwent hepatic resection after preoperative chemotherapy between 2008 and 2013 were included. Two radiologists blinded to the histopathology findings performed a consensus categorization of the marginal contrast effects of CRLM on CE-CT as follows: Group 1, smooth margin without enhancement; Group 2, smooth margin with an enhanced rim; and Group 3, fuzzy margin with/without an enhanced rim. The Kruskal-Wallis test was used to compare the imaging findings with the histological findings.

Results

The percentage of infarct-like necrosis was significantly higher in CRLM with smooth margins than in those with fuzzy margins (p<0.001, r=0.62). The percentage of viable cells was lowest in CRLM with smooth margins without enhancement (p<0.001, r=0.60).

Conclusions

Our findings suggest that the type of necrosis is related to the nature of the margins, and the presence of residual cells are related to peripheral enhancement.

Advances in knowledge

In CRLM, following chemotherapy, the presence of residual cells and dangerous haloes is related to the contrast effect of the tumor margins, suggesting that tumor angiogenesis affects the contrast effect.
QTL analysis of vegetative phase change in natural accessions ofArabidopsis thaliana
Authors: Doody Erin , Zha Yuqi , He Jia , Poethig Scott
Published: October 2021

Shoot development in plants is divided into two phases, a vegetative phase and a reproductive phase. Vegetative growth also has two distinct juvenile and adult phases, the transition between which is termedvegetative phase change. To understand how this developmental transition is regulated in natural populations of plants, we grew a group of 70 accessions ofArabidopsis thalianaand measured the appearance of traits associated with vegetative and reproductive phase change. We found that these transitions were uncorrelated, implying they are regulated by different mechanisms. Furthermore, an analysis of accessions from Central Asia revealed that precocious changes in leaf shape poorly correlated with the timing of abaxial trichome production (an adult trait) and with variation in the level of miR156 (a key regulator of vegetative phase change). This suggests the timing of vegetative phase change is regulated by more than one mechanism. To identify the genes responsible for the precocious vegetative phenotype of these accessions, we used a set of recombinant inbred lines derived from a cross between the standard lab strain, Col-0, and one of these accessions, Shakdara. We identified eight quantitative trait loci involved in the vegetative phase change, some of which regulated different components of leaf development. All of these loci were distinct from those that regulate flowering time. These data provide the foundation for future studies to identify the loci and the regulatory networks responsible for natural variation in the timing of vegetative phase change inA. thaliana.
Nostoc talks back: Temporal patterns of differential gene expression during establishment of the Anthoceros-Nostoc symbiosis
Authors: Chatterjee Poulami , Schafran Peter , Li Fay-Wei , Meeks John C
Published: October 2021

Endosymbiotic association between hornworts and dinitrogen-fixing cyanobacteria form when the plant is limited for combined nitrogen (N). We generated RNA-Seq data to examine the temporal gene expression patterns during culture of N-starved Anthoceros punctatus in the absence and presence of the symbiotically competent cyanobacterium Nostoc punctiforme. Symbiotic nitrogenase activity commenced within 5 days of coculture reaching a maximal by 14 days. In symbiont-free gametophytes, chlorophyll content, chlorophyll fluorescence characteristics and transcription of genes encoding light harvesting and reaction center proteins, as well as the small subunit of ribulose-bisphosphate-carboxylase/oxygenase, were downregulated. The downregulation was complemented in a temporal pattern corresponding to the N. punctiforme provision of N2-derived ammonium. The impairment and complementation of photosynthesis was the most distinctive response of A. punctatus to N-starvation. Increases in transcription of ammonium and nitrate transporters and their N. punctiforme-dependent complementation was also observed. The temporal patterns of differential gene expression indicated N. punctiforme transmits signals to A. punctatus both prior to, and after its provision of fixed N. This is the only known temporal transcriptomic study during establishment of a symbiotic nitrogen-fixing association in this monophyletic evolutionary lineage of land plants.

Highlights

Temporal RNA-Seq analysis revealed how symbiotic cyanobacteria impact plant partners’ global gene expression and elucidated the nature of bidirectional communications between the partners
Appropriate tension sensitivity of α-catenin ensures rounding morphogenesis of epithelial spheroids
Authors: Nishimura Ryosuke , Kato Kagayaki , Saida Misako , Kamei Yasuhiro , Takeda Masahiro , Miyoshi Hiromi , Yamagata Yutaka , Amano Yu , Yonemura Shigenobu
Published: October 2021

The adherens junction (AJ) is an actin filament-anchoring junction. It plays a central role in epithelial morphogenesis through cadherin-based recognition and adhesion among cells. The stability and plasticity of AJs are required for the morphogenesis. An actin-binding α-catenin is an essential component of the cadherin-catenin complex and functions as a tension transducer that changes its conformation and induces AJ development in response to tension. Despite much progress in understanding molecular mechanisms of tension sensitivity of α-catenin, its significance on epithelial morphogenesis is still unknown. Here we show that the tension sensitivity of α-catenin is essential for epithelial cells to form round spheroids through proper multicellular rearrangement. Using a novel in vitro suspension culture model, we found that epithelial cells form round spheroids even from rectangular-shaped cell masses with high aspect ratios without using high tension and that hypersensitive mutants affected this morphogenesis. Analyses of AJ formation and cellular tracking during rounding morphogenesis showed cellular rearrangement, probably through AJ remodeling. The rearrangement occurs at the cell mass level, but not single-cell level. Hypersensitive α-catenin mutant-expressing cells did not show cellular rearrangement at the cell mass level, suggesting that proper AJ plasticity requires appropriate tension sensitivity of α-catenin.
Evaluation of 6 MALDI-Matrices for 10 µm lipid imaging and on-tissue MSn with AP-MALDI-Orbitrap
Authors: Angerer Tina B. , Bour Jerome , Biagi Jean-Luc , Moskovets Eugene , Frache Gilles
Published: October 2021

Mass spectrometry imaging (MSI) is a technique uniquely suited to localize and identify lipids in a tissue sample. Using an AP-MALDI UHR source coupled to an Orbitrap Elite, numerous lipid locations and structures can be determined in high mass resolution spectra and at cellular spatial resolution, but careful sample preparation is necessary. We tested 11 protocols on serial brain sections for the commonly used MALDI matrices, CHCA, Norharmane, DHB, DHAP, THAP, and DAN, in combination with tissue washing and matrix additives, to determine the lipid coverage, signal intensity, and spatial resolution achievable with AP-MALDI. In positive ion mode, the most lipids could be detected with CHCA and THAP, while THAP and DAN without additional treatment offered the best signal intensities. In negative ion mode, DAN showed the best lipid coverage and DHAP performed superior for Gangliosides. DHB produced intense cholesterol signals in the white matter. 155 lipids were assigned in positive (THAP), 137 in negative ion mode (DAN) and 76 lipids were identified using on tissue tandem-MS. The spatial resolution achievable with DAN was 10 μm, confirmed with on tissue line-scans. This enabled the association of lipid species to single neurons in AP-MALDI images. The results show that the performance of AP-MALDI is comparable to vacuum MALDI techniques for lipid imaging.

Abstract Figure
Non-specific effects of a CINNAMATE-4-HYDROXYLASE inhibitor on auxin homeostasis
Authors: El Houari Ilias , Klíma Petr , Baekelandt Alexandra , Staswick Paul , Uzunova Veselina , Del Genio Charo I. , Steenackers Ward , Dobrev Petre I. , Novák Ondrej , Napier Richard , Petrášek Jan , Inzé Dirk , Boerjan Wout , Vanholme Bartel
Published: October 2021

Chemical inhibitors are often implemented for the functional characterization of genes to overcome the limitations associated with genetic approaches. Although being a powerful tool, off-target effects of these inhibitors are easily overlooked in a complex biological setting. Here we illustrate the implications of such secondary effects by focusing on piperonylic acid (PA), an inhibitor of CINNAMATE-4-HYDROXYLASE (C4H) that is often used to investigate the involvement of lignin during plant growth and development. When supplied to plants, we found that PA is recognized as a substrate by GRETCHEN HAGEN 3.6 (GH3.6), an amido synthetase involved in the formation of the auxin catabolite indole-3-acetic acid (IAA)-Asp. By competing for the same enzyme, PA interferes with auxin conjugation, resulting in an increase in cellular auxin concentrations. These increased auxin levels likely further contribute to an increase in adventitious rooting previously observed upon PA-treatment. Despite the focus on GH3.6 in this report, PA is conjugated by an array of enzymes and their subsequent reduced activity on native substrates could potentially affect a whole set of physiological processes in the plant. We conclude that surrogate occupation of the endogenous conjugation machinery in the plant by exogenous compounds is likely a more general phenomenon that is rarely considered in pharmacological studies. Our results hereby provide an important basis for future reference in studies using chemical inhibitors.
A thermodynamic model of bacterial transcription
Authors: Qian Jin , Dunlap David , Finzi Laura
Published: October 2021

Transcriptional pausing is highly regulated by the template DNA and nascent transcript sequences. Here, we propose a thermodynamic model of transcriptional pausing, based on the thermal energy of transcription bubbles and nascent RNA structures, to describe the kinetics of the reaction pathways between active translocation, intermediate, backtracked, and hairpin-stabilized pauses. The model readily predicts experimentally detected pauses in high-resolution optical tweezers measurements of transcription. Unlike other models, it also predicts the effect of tension and the GreA transcription factor on pausing.
Binding Affinity Estimation From Restrained Umbrella Sampling Simulations
Authors: Kumar Vivek Govind , Agrawal Shilpi , Suresh Kumar Thallapuranam Krishnaswamy , Moradi Mahmoud
Published: October 2021

The protein-ligand binding affinity quantifies the binding strength between a protein and its ligand. Computer modeling and simulations can be used to estimate the binding affinity or binding free energy using data- or physics-driven methods or a combination thereof. Here, we discuss a purely physics-based sampling approach based on biased molecular dynamics (MD) simulations, which in spirit is similar to the stratification strategy suggested previously by Woo and Roux. The proposed methodology uses umbrella sampling (US) simulations with additional restraints based on collective variables such as the orientation of the ligand. The novel extension of this strategy presented here uses a simplified and more general scheme that can be easily tailored for any system of interest. We estimate the binding affinity of human fibroblast growth factor 1 (hFGF1) to heparin hexasaccharide based on the available crystal structure of the complex as the initial model and four different variations of the proposed method to compare against the experimentally determined binding affinity obtained from isothermal calorimetry (ITC) experiments. Our results indicate that enhanced sampling methods that sample along the ligand-protein distance without restraining other degrees of freedom do not perform as well as those with additional restraint. In particular, restraining the orientation of the ligands plays a crucial role in reaching a reasonable estimate for binding affinity. The general framework presented here provides a flexible scheme for designing practical binding free energy estimation methods.
Dynamic analysis of a helical geared rotor-bearing system with composite rotating shafts
Authors: Chen Ying-Chung , Cheng Xu Feng , Choi Siu-Tong
Published: October 2021

Purpose

This study aims to study the dynamic characteristics of a helical geared rotor-bearing system with composite material rotating shafts.

Design/methodology/approach

A finite element model of a helical geared rotor-bearing system with composite material rotating shafts is developed, in which the rotating shafts of the system are composed of composite material and modeled as Timoshenko beam; a rigid mass is used to represent the gear and their gyroscopic effect is taken into account; bearings are modeled as linear spring-damper; and the equations of motion are obtained by applying Lagrange’s equation. Natural frequencies, mode description, lateral responses, axial responses, lamination angles, lamination numbers, gear mesh stiffness and bearing damping coefficients are investigated.

Findings

The desired mechanical properties could be constructed using different lamination numbers and fiber included angles by composite rotating shafts. The frequency of the lateral module decreases as the included angle of the fibers and the principal shaft of the composite material rotating shaft increase. Because of the gear mesh stiffness increase, the resonance frequency of the coupling module of the system decreases, the lateral module is not influenced and the steady-state response decreases. The amplitude of the steady-state lateral and axial responses gradually decreases as the bearing damping coefficient increases.

Practical implications

The model of a helical geared rotor-bearing system with composite material rotating shafts is established in this paper. The dynamic characteristics of a helical geared rotor-bearing system with composite rotating shafts are investigated. The numerical results of this study can be used as a reference for subsequent personnel research.

Originality/value

The dynamic characteristics of the geared rotor-bearing system had been reported in some literature. However, the dynamic analysis of a helical geared rotor-bearing system with composite material rotating shafts is still rarely investigated. This paper shows some novel results of lateral and axial response results obtained by different lamination angles and different lamination numbers. In the future, it makes valuable contributions for further development of dynamic analysis of a helical geared rotor-bearing system with composite material rotating shafts.