bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstruction of Completely Circumferentially Degloved Thumb Using Omental Flap and Tubular Split-thickness Skin Graft
Authors: Suito Motomu , Abe Naoki , Hirasawa Chihiro , Aisaka Tetsuya , Sakai Hiroshi
Published: October 2021

Various types of thin flaps have been used for reconstruction in cases of complete circumferential degloving injuries of digits (Urbaniak classification class III). The omental flap has extensive, pliable, and well-vascularized tissue and helps prevent bone resorption of the distal phalange that can result from avascular necrosis. A 31-year-old right-handed man with class III left thumb injury and compartment syndrome of the left forearm was treated successfully with a free omental flap wrapped around the thumb and then covered with a tubular split-thickness skin graft. The postoperative course was good, except that the distal third of the phalange of the thumb was resected because of insufficient omentum volume transplanted to the thumb tip resulting from omental volume bias in the distal part of the thumb. Bone scintigraphy 1 year after injury showed technetium-99m accumulation in the remaining two-thirds of the distal phalange, although there was no blood supply before the reconstruction. The advantages of our treatment method are that the thickness of the reconstructed digits can be adjusted by the amount of the omental flap. Skin grafting can be simplified; and with multiple digital injuries, separated fingers can be reconstructed in a single operation by wrapping each digit with a divided omental flap. Use of the free omental flap and tubular split-thickness skin graft is a therapeutic reconstruction option for Urbaniak class III injury.
Antibacterial action mechanisms of trypsin inhibitors
Authors: de Souza Nascimento Amanda Maria , Rodrigues Matias Lídia Leonize , de Oliveira Segundo Victor Hugo , Piuvezam Grasiela , Passos Thaís Souza , Damasceno Karla Suzanne Florentino da Silva Chaves , Morais Ana Heloneida de Araújo
Published: October 2021

Introduction:

Infectious diseases caused by bacteria represent one of the challenges in human healthcare, mostly caused by resistant bacteria, increasing the treatment cost, and fatal health complications. Researchers worldwide seek new therapeutic strategies to combat these highly resistant bacteria. Trypsin inhibitor peptides or proteins have innumerous bioactivities, such as antibacterial activity, which makes them potential candidates to treat diseases caused by bacteria. Thus, this study protocol describes a systematic review concerning the action mechanisms related to these molecules’ antibacterial activity.

Methods:

This systematic review protocol was elaborated according to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). The databases PubMed, ScienceDirect, Scopus, Web of Science, and Virtual Health Library will be used. Experimental studies carried out with rats and/or mice of both sexes, without water or diet restriction and in vitro (bacterial culture) studies and in cell, treated with trypsin inhibitor-type peptides or proteins that have a possible antibacterial action will be included. If at least two studies present clinical and/or methodological and/or statistical homogeneity, a meta-analysis will be carried out at the end of the analysis. The selection of studies, data extraction, and methodological quality assessment will be performed independently by two reviewers.

Results:

This protocol will be the basis for a systematic review. It is expected to identify several manuscripts highlighting the mechanisms related to the action of trypsin inhibitor peptides or proteins on bacteria.

Conclusion:

The systematic review based on this protocol will gather knowledge about trypsin inhibitor peptides or proteins’ antibacterial action mechanisms. It will provide subsidies for new research involving these molecules’ application against infectious diseases caused by bacteria.

Ethics and dissemination:

The present work does not involve any humans or animals; therefore, ethical approval is not needed.

Prospero Registration Number:

This review was registered with the International Register of Prospective Systematic Reviews on Jun 11, 2020 (registration: CRD42020189069). Available at: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=189069.
Vocal fold sulci – what are the current options for and outcomes of treatment?
Authors: Avellaneda Juan Carlos , Allen Jacqueline E.
Published: October 2021

Purpose of review

Sulcus vocalis is a benign condition of the vocal folds that, according to its severity, can affect the quality of the voice of those who have it. Voice symptoms can range from mild to severe, affecting the quality of life of patients with this condition. Although different surgical and no surgical options have been described, no gold standard treatment has been described.

Recent findings

New evidence supports congenital, inflammatory, and acquired theories for sulcus vocalis. Also, recent literature demonstrated the role of the epithelium in the pathogenesis, which makes the absence of superficial lamina propria no longer the only accepted hypothesis. Technological developments improved the in-office diagnostics capabilities for this condition, but vocal fold palpation remains the gold standard. Different benign laryngeal conditions are associated with sulcus vocalis and knowing when to treat those is very important. Different treatment options are available for sulcus vocalis, however, results are diverse and no strong recommendations for one over the other can be made.

Progress continues to be made in our understanding of sulcus vocalis from diagnosis to treatment. Novel and promising therapeutic strategies have been recently developed for this condition; however, more data and investigations are needed to improve their accuracy and reproducibility.
Global Burden of Orofacial Clefts and the World Surgical Workforce
Authors: Massenburg Benjamin B. , Hopper Richard A. , Crowe Christopher S. , Morrison Shane D. , Alonso Nivaldo , Calis Mert , Donkor Peter , Kreshanti Prasetyanugraheni , Yuan Jie
Published: October 2021

Background:

Orofacial clefts are one of the most common congenital anomalies, but this disease burden is unevenly distributed worldwide. The authors hypothesize that this burden falls disproportionately on the countries with the smallest surgical workforce or lowest Socio-Demographic Index, rather than those with the highest prevalence of disease.

Methods:

The authors estimated the prevalence and disease burden of orofacial clefting from 1990 to 2017 in 195 countries using the Global Burden of Disease methodology. Prevalence and disability-adjusted life-years were compared geographically, temporally, and against the size of the national surgical workforce, Socio-Demographic Index, and income status. Linear and logarithmic regressions were performed.

Results:

In 2017, the prevalence of orofacial clefting was estimated to be 10.8 million people, representing a disease burden of 652,084 disability-adjusted life-years, with most of this disease burden experienced by low- and middle-income countries (94.1%). From 1990 to 2017, there was a decrease in disease burden (-70.2%) and prevalence (-4.9%). There was negative logarithmic association between surgical workforce size and disease burden, with a surgical workforce of greater than six providers per 100,000 population (3.6 disability-adjusted life-years versus 22.4 disability-adjusted life-years per 100,000 population; p < 0.0001).

Conclusions:

Burden of orofacial clefting has a strong negative association with the size of the surgical workforce, suggesting that strengthening the surgical workforce will help alleviate this burden. Epidemiologic data on countries and regions with inadequate surgical workforces and high disease burden should guide future research efforts and allocation of resources, and guide the treatment and educational goals of international charitable organizations.
The Incidence of Occult Malignant and High-Risk Pathologic Findings in Breast Reduction Specimens
Authors: Razavi Seyed Amirhossein , Hart Alexandra M. , Betarbet Udayan , Li Xiaoxian , Carlson Grant W. , Losken Albert
Published: October 2021

Background:

The goal of this study was to determine the incidence of occult malignancy and high-risk breast pathologic findings in patients who undergo breast reduction procedures.

Methods:

Medical records of consecutive patients who underwent reduction mammaplasty performed by the senior authors (A.L. and G.W.C.) at Emory University Hospital between 1997 and 2018 were reviewed. Data regarding patient demographics, personal or family history of malignancy, operative technique, pathologic findings, and follow-up were extracted. Patients were categorized into two groups, those with and those without breast cancer. Group A patients underwent reduction for symptomatic macromastia, and group B underwent contralateral reduction for unilateral breast cancer treated with oncoplastic partial or total breast cancer reconstruction. Pathologic findings were divided into four groups; normal, benign, high-risk, and malignant.

Results:

A total 1014 patients (1419 breast reductions) were included in the study. Comparing groups A and B, mean age was 37.8 ± 16.2 years versus 54.5 ± 11.1 years (p < 0.001), mean body mass index was 34.1 ± 7.6 kg/m2 versus 33.3 ± 7.4 kg/m2 (p = 0.2), and average reduction weight was 875.6 ± 491 g versus 723.7 ± 438 g (p < 0.001). The incidence of high-risk or malignant lesions was 1.8 percent (n = 15) in group A and 8 percent (n = 49) in group B (p < 0.001). On multivariable logistic regression analysis, age and personal history of breast cancer were positive predictors for high-risk and malignant lesions.

Conclusions:

The incidence of abnormal pathologic findings in breast reduction specimens is not uncommon, and occult malignancy or high-risk lesions can be found, especially in patients with contralateral breast cancer. Appropriate specimen orientation, diligence with checking the pathologic findings, and open communication with the pathologist are crucial.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
The Goldilocks Procedure with and without Implant-Based Immediate Breast Reconstruction in Obese Patients: The Mayo Clinic Experience
Authors: Bustos Samyd S. , Nguyen Minh-Doan , Harless Christin A. , Tran Nho V. , Martinez-Jorge Jorys , Lin Jason , Forte Antonio J. , Casey William J. , Boughey Judy C. , McLaughlin Sarah A. , Gray Richard , Manrique Oscar J.
Published: October 2021

Background:

Obesity is a risk factor for complications in breast reconstruction. Thus, implant-based immediate breast reconstruction in obese women may be controversial. The authors analyzed obese patients who underwent skin-sparing mastectomy using Wise-pattern incisions (Goldilocks procedure) and compared outcomes between two groups: Goldilocks with immediate breast reconstruction and Goldilocks only.

Methods:

A retrospective review was performed of patients with a body mass index of 30 kg/m2 or higher who underwent the Goldilocks procedure at the Mayo Clinic Health System from 2012 to 2019. Data were extracted from electronic medical records. Minor complications (partial-thickness wound dehiscence or flap necrosis, or tissue expander/implant malposition) and major complications (full-thickness wound dehiscence or flap necrosis, capsular contracture, tissue expander/implant explantation, or unplanned reoperation or readmission) were compared between groups. Patient-reported outcomes using BREAST-Q questionnaires were also assessed.

Results:

One hundred five patients (181 breasts) were included. Mean ± SEM age and body mass index were 57.1 ± 10.4 years and 37.9 ± 5.8 kg/m2 for the Goldilocks-only group and 51.5 ± 1.1 years and 35.5 ± 0.4 kg/m2 for the Goldilocks with immediate breast reconstruction group, respectively. Median follow-up time was 15.1 months (interquartile range, 10.0 to 28.6 months). Overall, 96 breasts underwent the Goldilocks-only procedure and 85 Goldilocks with immediate breast reconstruction. Multivariable analyses revealed a higher rate of minor complications (adjusted hazard ratio, 2.83; 95 percent CI, 1.22 to 7.02) and major complications (adjusted hazard ratio, 2.26; 95 percent CI, 1.25 to 4.24) in the Goldilocks with immediate breast reconstruction group compared with the Goldilocks-only group, at any given time. Patient satisfaction was not statistically different between groups.

Conclusions:

The Goldilocks procedure is a feasible breast reconstructive option in obese patients; however, when it is performed with immediate breast reconstruction, it is associated with higher rates of complications. For patients with a body mass index of 40 kg/m2 or greater, the authors recommend the Goldilocks-only procedure or delayed reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Expanded Role of Alar Contour Grafts
Authors: Rohrich Rod J. , Durand Paul D.
Published: October 2021

Alar rim deformities are among the most common problems affecting patients undergoing both primary and secondary rhinoplasty. They can be caused by several factors such as congenital hypoplasia or malpositioning of the lateral crura, and from acquired surgical weakening during rhinoplasty. Even though altering the structure of the lower lateral cartilage complex can help prevent and correct alar rim deformities, this may not always allow for sufficient control of the alar rim. Alar contour grafts have been proven efficacious not just in the treatment of specific rim deformities but also in their prevention. In this article, the authors present four types of alar contour grafts and discuss their expanded role in the prevention and treatment of alar rim deformities.
Compliance to kangaroo mother care best practice: an evidence-based implementation project
Authors: Siraneh Yibeltal , Berhane Melkamu , Abraham Gelila , Feyissa Garumma Tolu , Morankar Sudhakar
Published: October 2021

Background:

Worldwide about 13 million babies are born prematurely every year. Kangaroo mother care (KMC) is a proven, acceptable and feasible method to decrease the mortality rate of premature infants. Reviewing current KMC practices, implementing in the context and auditing the compliance would benefit the promotion evidence-based practice (EBP), which was not well known in the study area.

Objectives:

The main objective of the study was to increase awareness of EBP for KMC in the neonatal care unit of a public hospital through identifying local barriers and facilitators, and to measure compliance with best practice recommendations.

Methods:

The current KMC best practice quality improvement project was conducted between March and May 2018. The project team was established for this implementation project. Six KMC best practice audit criteria were used to evaluate the compliance at baseline and endline using the Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research into Practice audit and feedback tool. All (20) clinical staff who were working in the neonatal care unit were included in the study. Based on the baseline audit result, gaps and barriers were identified and discussed, and implementation strategies specific to the local setting were developed to mitigate the gaps. Baseline results were compared with the final follow-up audit result to measure change in compliance. Again, these data were compared with other studies to identify the sustainability of the project in a clinical setting.

Results:

A total of 80 cases (baseline 20 and implementation 60) were observed demonstrating KMC procedures. Study found that follow-up compliance rates for all criteria improved compared with baseline audit; for example, criterion 5 (assessment of infant's condition) improved from 20% during baseline to 90% during follow-up and criterion 3 (parent/family received counselling) improved from 30 to 95%.

Conclusion:

The current study demonstrated that EBP training and frequent supportive supervision translated in improved compliance to best available evidence to KMC in a resource-limited setting.
Management of nipple pain or trauma in breastfeeding mothers in a hospital setting: a best practice implementation project
Authors: Yang Lixia , Wang Xiaoyang , Luo Yin , Sun Fengjiao , Wu Minyan , Huang Yacui , Zhang Qian , Liu Yawei , Xiao Lin , Wang Ning
Published: October 2021

Introduction and aims:

Breastfeeding is one of the best ways to ensure healthy growth and development of an infant. Nipple pain and trauma are common complications associated with breastfeeding, which render it difficult for the mother to continue breastfeeding. The aim of this project was to promote evidence-based practice in the management of nipple pain or trauma for breastfeeding mothers in a large tertiary hospital in China.

Methods:

The project was conducted using the Joanna Briggs Institute framework and Practical Application of Clinical Evidence System. Six audit criteria were applied in baseline and follow-up audits to assess compliance in practice with best practice recommendations. The Getting Research into Practice tool was used to help analyze barriers to the fulfillment of each audit criterion based on the baseline audit results. Implementation strategies were discussed and then undertaken to overcome the barriers and bring changes to the current practice.

Results:

The baseline audit results demonstrated poor compliance in nipple pain or trauma management practice with all of the six criteria. Significant improvements were achieved in the follow-up audit. Specifically, the compliance rate increased from 15 to 100% for criterion 1 and from 2 to 93% for criterion 2. For criteria 3, 4, 5 and 6, the compliance rate increased from 0 to 90, 85, 100 and 86%, respectively.

Conclusion:

The current evidence-based implementation project was successfully conducted and achieved great improvement in the management of nipple pain or trauma associated with breastfeeding. Continuous effort is required to maintain changes and further improve practice.
Regional probabilistic situational awareness and forecasting of COVID-19
Authors: Engebretsen Solveig , Palomares Alfonso Diz-Lois , Rø Gunnar , Kristoffersen Anja Bråthen , Lindstrøm Jonas Christoffer , Engø-Monsen Kenth , Hin Chan Louis Yat , Dale Ørjan , Eriksson Midtbø Jørgen , Stenerud Kristian Lindalen , Di Ruscio Francesco , White Richard , Frigessi Arnoldo , de Blasio Birgitte Freiesleben
Published: October 2021

Mathematical models and statistical inference are fundamental for surveillance and control of the COVID-19 pandemic. Several aspects cause regional heterogeneity in disease spread. Individual behaviour, mobility, viral variants and transmission vary locally, temporally and with season, and interventions and vaccination are often implemented regionally. Therefore, we developed a new regional changepoint stochastic SEIR metapopulation model. The model is informed by real-time mobility estimates from mobile phone data, laboratory-confirmed cases, and hospitalisation incidence. To estimate locally and time-varying transmissibility, case detection probabilities, and missed imported cases, we present a new sequential Approximate Bayesian Computation method allowing inference in useful time, despite the high parametric dimension. We test our approach on Norway and find that three-week-ahead predictions are precise and well-calibrated, suitable for real-time surveillance.

Significance

We developed a regional infectious disease spread model focussing on operational usefulness in real time. The model is informed by near real-time mobile phone mobility data, laboratory-confirmed cases, and hospitalisation incidence. The model is used to estimate reproduction numbers and provide regional predictions of future hospital beds. Regional reproduction numbers are important due spatio-temporal heterogeneity due to for example local interventions. We assume different regional reproduction numbers for different periods of the epidemic. We propose a new calibration method to estimate the reproduction numbers and other parameters of the model, tailored to handle the increasingly high dimension of parameters over time. The model has been successfully used for local situational awareness and forecasting for the Norwegian health authorities during COVID-19.
Parallel functional subnetworks embedded in the macaque face patch system
Authors: Park Soo Hyun , Koyano Kenji W. , Russ Brian E. , Waidmann Elena N. , McMahon David B. T. , Leopold David A.
Published: October 2021

During normal vision, our eyes provide the brain with a continuous stream of useful information about the world. How visually specialized areas of the cortex, such as face-selective patches, operate under natural modes of behavior is poorly understood. Here we report that, during the free viewing of videos, cohorts of face-selective neurons in the macaque cortex fractionate into distributed and parallel subnetworks that carry distinct information. We classified neurons into functional groups based on their video-driven coupling with fMRI time courses across the brain. Neurons from each group were distributed across multiple face patches but intermixed locally with other groups at each recording site. These findings challenge prevailing views about functional segregation in the cortex and underscore the importance of naturalistic paradigms for cognitive neuroscience.

One-Sentence Summary

Natural visual experience reveals parallel functional subnetworks of neurons embedded within the macaque face patch system
Robust enhancer-gene regulation identified by single-cell transcriptomes and epigenomes
Authors: Xie Fangming , Armand Ethan J. , Yao Zizhen , Liu Hanqing , Bartlett Anna , Behrens M. Margarita , Li Yang Eric , Lucero Jacinta D. , Luo Chongyuan , Nery Joseph R. , Pinto-Duarte Antonio , Poirion Olivier , Preissl Sebastian , Rivkin Angeline C. , Tasic Bosiljka , Zeng Hongkui , Ren Bing , Ecker Joseph R. , Mukamel Eran A.
Published: October 2021

Integrating single-cell transcriptomes and epigenomes across diverse cell types can link genes with the cis-regulatory elements (CREs) that control expression. Gene co-expression across cell types confounds simple correlation-based analysis and results in high false prediction rates. We developed a procedure that controls for co-expression between genes and integrates multiple molecular modalities, and used it to identify >10,000 gene-CRE pairs that contribute to gene expression programs in different cell types in the mouse brain.
PREPRINT: Mechanisms of Motoric Cognitive Risk – hypotheses based on a systematic review and meta-analysis of longitudinal cohort studies of older adults
Authors: Mullin Donncha S. , Cockburn Alastair , Welstead Miles , Luciano Michelle , Russ Tom C. , Muniz-Terrera Graciela
Published: October 2021

We aimed to refine the hypothesis that Motoric Cognitive Risk (MCR), a syndrome combining measured slow gait speed and self-reported cognitive complaints, is prognostic of incident dementia and other major causes of morbidity in older age. We propose mechanisms on the relationship between motor and cognitive function and describe a roadmap to validate these hypotheses. We systematically searched major electronic databases from inception to August 2021 for original longitudinal cohort studies of adults aged ≥60 years that compared an MCR group to a non-MCR group with any health outcome. Fifteen cohorts were combined by meta-analysis. Participants with MCR were at an increased risk of cognitive impairment (adjusted hazard ratio [aHR] 1.76, 95%CI 1.49-2.08; I2=24.9%), dementia (aHR 2.12, 1.85-2.42; 33.1%), falls (adjusted Relative Risk 1.38, 1.15-1.66; 62.1%), and mortality (aHR 1.49, 1.16-1.91; 79.2%). The prognostic value of MCR is considerable and mechanisms underlying the syndrome are proposed.

Systematic review registration

PROSPERO CRD42020225183.
Protocol for 18F-PSMA PET imaging in staging and management of prostate cancer – a retrospective cohort study
Authors: Byrne Matthew H V , Ranasinha Nithesh , Bryant Richard J , Hamdy Freddie C , Leslie Tom , Miah Saiful , Gleeson Fergus , MacPherson Ruth , Tuthill Mark , Protheroe Andy , Camilleri Philip , Turner Phil , Sabharwal Ami , Andrade Gerard , Lamb Alastair D
Published: October 2021

Background

MRI, bone scan, and CT staging is recommended in the staging of prostate cancer. However, prostate-specific membrane antigen positron emission tomography (PSMA PET) could be superior in detection of local and distant prostate cancer cells. Most PSMA PET scans for prostate cancer are performed with a Gallium-68 ligand, with the Fluorine-18 (18F) ligand being introduced more recently. Methods: We will conduct a retrospective review of electronic patient records for all consecutive patients who underwent preoperative 18F-PSMA PET scan for prostate cancer from its introduction at our centre in 2019. We will compare PET scans with other imaging modalities and evaluate its use in diagnosis and management decisions for prostate cancer.

Conclusions

Understanding the role of 18F-PSMA PET in diagnosis and management could influence the diagnostic pathway of primary and secondary prostate cancer.

Trial registration

Not applicable.
White matter microstructure in Parkinson’s disease with and without elevated REM sleep muscle tone
Authors: Patriat Rémi , Pisharady Pramod K. , Amundsen-Huffmaster Sommer , Linn-Evans Maria , Howell Michael , Chung Jae Woo , Petrucci Matthew N. , Videnovic Aleksandar , Holker Erin , De Kam Joshua , Tuite Paul , Lenglet Christophe , Harel Noam , MacKinnon Colum D.
Published: October 2021

People with Parkinson’s disease who have elevated muscle activity during rapid eye movement sleep (REM sleep without atonia) typically have worse motor and cognitive impairment compared to those with normal muscle atonia during REM sleep. This study used tract-based spatial statistics to compare diffusion MRI measures of fractional anisotropy, radial, mean and axial diffusivity (measures of axonal microstructure based on the directionality of water diffusion) in white matter tracts between people with Parkinson’s disease with and without REM sleep without atonia and controls and their relationship to measures of motor and cognitive function. Thirty-eight individuals with mild-to-moderate Parkinson’s disease and twenty-one matched control subjects underwent ultra-high-field MRI (7Tesla), quantitative motor assessments of gait and bradykinesia, and neuropsychological testing. The Parkinson’s disease cohort was separated post-hoc into those with and without elevated chin or leg muscle activity during REM sleep based on polysomnography findings. Fractional anisotropy was significantly higher, and diffusivity significantly lower, in regions of the corpus callosum, projection, and association white matter pathways in the Parkinson’s group with normal REM sleep muscle tone compared to controls, and in a subset of pathways relative to the Parkinson’s disease group with REM sleep without atonia. The Parkinson’s disease group with elevated REM sleep muscle tone showed significant impairments in gait and upper arm speed compared to controls and significantly worse scores in specific cognitive domains (executive function, visuospatial memory) compared to the Parkinson’s disease group with normal REM sleep muscle tone. Regression analyses showed that gait speed and step length in the Parkinson’s disease cohort were predicted by measures of fractional anisotropy of the anterior corona radiata, whereas elbow flexion velocity was predicted by fractional anisotropy of the superior corona radiata. Visuospatial memory task performance was predicted by the radial diffusivity of the posterior corona radiata. These findings show that people with mild-to-moderate severity of Parkinson’s disease who have normal muscle tone during REM sleep demonstrate compensatory-like adaptations in axonal microstructure that are associated with preserved motor and cognitive function, but these adaptations are reduced or absent in those with increased REM sleep motor tone.
An increase in surface hydrophobicity mediates chaperone activity in N-chlorinated proteins
Authors: Varatnitskaya Marharyta , Fasel Julia , Müller Alexandra , Lupilov Natalie , Shi Yunlong , Fuchs Kristin , Krewing Marco , Jung Christoph , Jakob Timo , Sitek Barbara , Bandow Julia E. , Carroll Kate S. , Hoffmann Eckhard , Leichert Lars I.
Published: October 2021

Under physiological conditions, Escherichia coli RidA is an enamine/imine deaminase, which promotes the release of ammonia from reactive enamine/imine intermediates. However, when modified by hypochlorous acid (HOCl), as produced by the host defense, RidAHOCl turns into a potent chaperone-like holdase that can effectively protect the proteome of E. coli during oxidative stress. We previously reported that the activation of RidA’s chaperone-like function coincides with the addition of at least seven and up to ten chlorine atoms. These atoms are reversibly added to basic amino acids in RidAHOCl and removal by reducing agents leads to inactivation. Nevertheless, it remains unclear, which residues in particular need to be chlorinated for activation. Here, we employ a combination of LC-MS/MS analysis, a chemo-proteomic approach, and a mutagenesis study to identify residues responsible for RidA’s chaperone-like function. Through LC-MS/MS of digested RidAHOCl, we obtained direct evidence of the chlorination of one arginine residue (and, coincidentally, two tyrosine residues), while other N- chlorinated residues could not be detected, presumably due to the instability of the modification and its potential interference with a proteolytic digest. Therefore, we established a chemoproteomic approach using 5-(dimethylamino) naphthalene-1-sulfinic acid (DANSO2H) as a probe to label N-chlorinated lysines. Using this probe, we were able to detect the N-chlorination of six additional lysine residues. Moreover, using a mutagenesis study to genetically probe the role of single arginine and lysine residues, we found that the removal of arginines R105 and R128 leads to a substantial reduction of RidAHOCl’s chaperone activity. These results, together with structural analysis, confirm that the chaperone activity of RidA is concomitant with the loss of positive charges on the protein surface, leading to an increased overall protein hydrophobicity. Molecular modelling of RidAHOCl and the rational design of a RidA variant that shows chaperone activity even in the absence of HOCl further supports our hypothesis. Our data provide a molecular mechanism for HOCl-mediated chaperone activity found in RidA and a growing number of other HOCl-activated chaperones.
Cell region fingerprints enable highly precise single-cell tracking and lineage reconstruction
Authors: Cuny Andreas P. , Ponti Aaron , Kündig Tomas , Rudolf Fabian , Stelling Jörg
Published: October 2021

Experimental studies of cell growth, inheritance, and their associated processes by microscopy require accurate single-cell observations of sufficient duration to reconstruct the genealogy. However, cell tracking—assigning identical cells on consecutive images to a track—is often challenging due to imperfect segmentation, moving cells, or focus drift, resulting in laborious manual verification. Here, we propose fingerprints to identify problematic assignments rapidly. A fingerprint distance measures the similarity between cells in two consecutive images by comparing the structural information contained in the low frequencies of a Fourier transform. We show that it is broadly applicable across cell types and image modalities, provided the image has sufficient structural information. Our tracker (TracX) uses the concept to reject unlikely assignments, thereby substantially increasing tracking performance on published and newly generated long-term data sets from various species. For S. cerevisiae, we propose a comprehensive model for cell size control at the single-cell and population level centered on the Whi5 regulator. It demonstrates how highly precise tracking can help uncover previously undescribed single-cell biology.
DEAD-box RNA helicase 18 disrupts IRF3-binding to the interferon-β promoter
Authors: Xiao Xun , Wang Mohan , Zhao Wenkai , Fang Puxian , Zhou Yanrong , Wang Dang , Fang Liurong , Xiao Shaobo
Published: October 2021

The production of type I interferons (IFN-α/β) requires strict control to avoid excessive activation during viral infections. The binding of interferon regulatory factor 3 (IRF3) to the IFN-β promoter region in the nucleus is essential for IFN-β transcription; however, whether nuclear factors have important negative-regulatory roles in this process is largely unknown. By screening for IRF3-interacting partners in the nucleus, we identified DEAD-box RNA helicase 18 (DDX18) as an important negative regulator of intranuclear IRF3. Overexpression of DDX18 suppressed virus- and IRF3-induced IFN-β production, whereas knockdown of DDX18 expression or knockout of the DDX18 gene had opposite effects. Mechanistically, DDX18 interacts with IRF3 and decreases the binding of IRF3 to the IFN-β promoter after viral infection. DDX18 knockdown mice (Ddx18+/-) further demonstrated that DDX18 suppressed antiviral innate immunity in vivo. Thus, despite many members of the DDX family act as important positive regulators in the cytoplasm, DDX18 plays a unique “braking” role in balancing virus-induced type I IFN production.
Event-triggered STED imaging
Authors: Alvelid Jonatan , Damenti Martina , Testa Ilaria
Published: October 2021

The observation of protein organization during cellular signalling calls for imaging methods with increased spatial and temporal resolution. STED nanoscopy can access dynamics of nanoscale structures in living cells. However, the available number of recordable frames is often limited by photo-bleaching. Here, we present an automated method, event-triggered STED, which instantly (< 40 ms) images synaptic proteins with high spatial and temporal resolution (~30 nm, 2.5 Hz) in small regions upon and at the site of local calcium sensing.
Extensive sequence divergence of non-coding regions between Aspergillus fumigatus, a major fungal pathogen of humans, and its relatives
Authors: Brown Alec , Mead Matthew E. , Steenwyk Jacob L. , Goldman Gustavo H. , Rokas Antonis
Published: October 2021

Invasive aspergillosis is a deadly fungal disease; more than 400,000 patients are infected worldwide each year and the mortality rate can be as high as 50-95%. Of the ∼450 species in the genus Aspergillus only a few are known to be clinically relevant, with the major pathogen Aspergillus fumigatus being responsible for ∼50% of all invasive mold infections. Genomic comparisons of A. fumigatus to other Aspergillus species have historically focused on protein-coding regions. However, most A. fumigatus genes, including those that modulate its virulence, are also present in non-pathogenic close relatives of A. fumigatus. Our hypothesis is that differential gene regulation – mediated through the non-coding regions upstream of genes’ transcription start sites – contributes to A. fumigatus pathogenicity. To begin testing this, we compared non-coding regions up to 500 base pairs upstream of the first codon of single-copy orthologous genes from the two A. fumigatus reference strains Af293 and A1163 and eight closely related Aspergillus section Fumigati species. We found that non-coding regions showed extensive sequence variation and lack of homology across species. By examining the evolutionary rates of both protein-coding and non-coding regions in a subset of orthologous genes with highly conserved non-coding regions across the phylogeny, we identified 418 genes, including 25 genes known to modulate A. fumigatus virulence, whose non-coding regions exhibit a different rate of evolution in A. fumigatus. Examination of sequence alignments of these non-coding regions revealed numerous instances of insertions, deletions, and other types of mutations of at least a few nucleotides in A. fumigatus compared to its close relatives. These results show that closely related Aspergillus species that vary greatly in their pathogenicity exhibit extensive non-coding sequence variation and identify numerous changes in non-coding regions of A. fumigatus genes known to contribute to virulence.
SCS313 Serrano, a big trefoil selected for flowering ability and seed production
Authors: Rocha Dediel A. , Cordova Ulisses A. , Flaresso Jefferson , Stradiotto Joseli , Dalla-Costa Murilo
Published: October 2021

SCS313 Serrano is a tetraploid cultivar of Lotus uliginosus developed by the Research and Rural Extension Company of Santa Catarina, Brazil, to improve flowering ability and seed production in low-latitude regions. SCS313 Serrano was developed from the selection of individual plants of the cultivar Grasslands Maku. Seeds from the initial breeding population was bulked and used to establish a field trial with spaced plants. The plants were selected and classified as late or early, regarding the beginning of flowering, through visual evaluations based on the time for the beginning of flowering. Selected plants were transplanted to crossing blocks and seed harvested on individual plants; a progeny test was conducted, with four replications, through the establishment of approximately 100 genotypes in a field. This process was repeated for three consecutive cycles of recurrent selection. Considering the mean time for the beginning of flowering and vigor performance, the best five genotypes were selected as parental lines for the synthetic cultivar SCS313 Serrano. A morphological difference between SCS313 Serrano and Grasslands Maku is that SCS313 Serrano has absence of hairs in stems whereas Grasslands Maku has a medium stem hair density. In addition, SCS313 Serrano exhibits profuse flowering ability while Grasslands Maku exhibits very sparse seedhead formation. SCS313 Serrano exhibited good persistence under wet conditions and similar forage yields compared to other lotus commercial cultivars. Thus, SCS313 Serrano is recommended to be used as pasture in mixtures with grass in livestock systems, mainly on wet soils.
Text Mining Drug-Protein Interactions using an Ensemble of BERT, Sentence BERT and T5 models
Authors: Sui Xin , Wang Wanjing , Zhang Jinfeng
Published: October 2021

In this work, we trained an ensemble model for predicting drug-protein interactions within a sentence based on only its semantics. Our ensembled model was built using three separate models: 1) a classification model using a fine-tuned BERT model; 2) a fine-tuned sentence BERT model that embeds every sentence into a vector; and 3) another classification model using a fine-tuned T5 model. In all models, we further improved performance using data augmentation. For model 2, we predicted the label of a sentence using k-nearest neighbors with its embedded vector. We also explored ways to ensemble these 3 models: a) we used the majority vote method to ensemble these 3 models; and b) based on the HDBSCAN clustering algorithm, we trained another ensemble model using features from all the models to make decisions. Our best model achieved an F-1 score of 0.753 on the BioCreative VII Track 1 test dataset.
Geo-epidemiology of Malaria in Burkina Faso, 2013-2018: a recent re-increase
Authors: Bationo Cédric S. , Lokossou Virgil , Landier Jordi , Sylla Bry , Tougri Gauthier , Ouedraogo Boukary , Cissoko Mady , Moiroux Nicolas , Gaudart Jean
Published: October 2021

Background

After a global decline, malaria cases re-increases have been shown recently.

The aim of this analysis was to update the epidemiological facies of malaria in Burkina Faso (around 4% of malaria cases worldwide) by estimating weekly malaria incidences at health district levels, from 2013 to 2018, associated to environmental and meteorological factors.

Methods

Malaria cases and deaths weekly reports were extracted from the National Malaria Control Program for each health district from 2013 to 2018. Population data were extracted from the reports of the national statistics council. Environmental data were collected through remote sensing.

After estimating incidence through time and space, trend was assessed by an additive decomposition of the incidence and malaria seasons of transmission was estimated by change point analysis (PELT algorithm).

Incidence maps for each year of the study period were assessed to highlight spatial variability through years. Maps of rainfall, temperature, and vegetation (NDVI) were produced to characterize the health district environmental variability.

Results

In 2013, 775 cases /100,000 inhab.week were observed in average, and remain roughly constant until 2015. Malaria re-increased from 2016, reaching 2428 cases /100,000 inhab.week in 2018.

From 2013 to 2016, two transmission periods were observed: low from January to July (included) and high from August to December (included).

From 2017 to 2018, an intermediate transmission period from mid-November to early January intercalated between the low transmission period from mid-February to early June and the high transmission period from July to late December

From 2013 to 2015, the most affected districts were located in the center and central-eastern part of the country. From 2016 to 2018 all health districts, except those in the Sahel region, were affected with at least 45,000 cases per 100,000 persons/year. This south-to-north gradient was also observed with rainfall, temperature and NDVI.

Conclusion

Malaria incidences re-increased through years and across the country since 2016. But no modification of the environmental factor variability was observed during the same period, in time or space. The re-increase of malaria in Burkina Faso could be due to a real increase of the disease, or to a better access to diagnostic and cure, together with the development of the epidemiological information system.
The Effect of Bilingual Exposure on Language and Cognitive Development in Children Following Ischemic Stroke
Authors: Leung Kai Ian , Dlamini Nomazulu , Westmacott Robyn , Molnar Monika
Published: October 2021

AIM

While many children who experience ischemic stroke come from bilingual backgrounds, it is unclear whether bilingual exposure affects post-stroke development. Our research evaluates the effects of bilingual vs. monolingual exposure on linguistic/cognitive development post-stroke.

METHOD

An institutional stroke registry and medical charts were used to gather data on 237 children across 3 stroke-onset groups: neonatal - <28 days, first-year - 28 days to 12 months and childhood - 13 months to 18 years. The Pediatric Stroke Outcome Measure (PSOM) was administered at several times post-stroke, to evaluate cognition and linguistic development.

RESULTS

Bilingual children had better post-stroke performance on the language subscales, compared to monolinguals. An interaction with stroke-onset group was also observed, with monolinguals in the first-year group having worse outcomes.

INTERPRETATION

Overall, no detrimental effects of bilingualism were found on children’s post-stroke cognition and linguistic development. Our study suggests that a bilingual environment may facilitate language development in children post-stroke.
COVCOG 2: Cognitive and Memory Deficits in Long COVID: A Second Publication from the COVID and Cognition Study
Authors: Guo Panyuan , Ballesteros Alvaro Benito , Yeung Sabine P , Liu Ruby , Saha Arka , Curtis Lyn , Kaser Muzaffer , Haggard Mark P , Cheke Lucy G
Published: October 2021

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been often characterized as a respiratory disease. However, it is increasingly being understood as an infection that impacts multiple systems, and many patients report neurological symptoms. Indeed, there is accumulating evidence for neural damage in some individuals, with recent studies suggesting loss of gray matter in multiple regions particularly in the left hemisphere. There are a number of mechanisms by which COVID-19 infection may lead to neurological symptoms and structural and functional changes in the brain, and cognitive problems are one of the most commonly reported symptoms in those suffering from Long COVID—the chronic illness following COVID-19 infection that affects between 10–25% of sufferers. However, there is as yet little research testing cognition in Long COVID. The COVID and Cognition Study is a cross-sectional/longitudinal study aiming to understand cognitive problems in Long COVID. The first paper from the study explored the characteristics of our sample of 181 individuals who had suffered COVID-19 infection, and 185 who had not, and the factors that predicted ongoing symptoms and self-reported cognitive deficits. In this second paper from the study, we assess this sample on tests of memory, language and executive function. We hypothesize that performance on “objective” cognitive tests will reflect self-reported cognitive symptoms. We further hypothesize that some symptom profiles may be more predictive of cognitive performance than others, perhaps giving some information as to mechanism. We found a consistent pattern of memory deficits in those that had suffered COVID-19 infection, with deficit increasing with severity of self-reported ongoing symptoms. Fatigue/Systemic symptoms during the initial illness and ongoing neurological symptoms were predictive of cognitive performance.
An evolutionarily conserved stop codon enrichment at the 5’ ends of mammalian piRNAs
Authors: Bornelöv Susanne , Czech Benjamin , Hannon Gregory J
Published: October 2021

PIWI-interacting RNAs (piRNAs) are small RNAs required to recognize and silence transposable elements. The 5’ ends of mature piRNAs are defined through cleavage of long precursor transcripts, primarily by Zucchini (Zuc). Zuc-dependent cleavage typically occurs immediately upstream of a uridine. However, Zuc lacks sequence preference in vitro, pointing towards additional unknown specificity factors. We examined murine piRNAs and revealed a strong and specific enrichment of three sequences (UAA, UAG, UGA)— corresponding to stop codons—at piRNA 5’ ends. Stop codon sequences were also enriched immediately after piRNA processing intermediates, reflecting their Zuc-dependent tail-to-head arrangement. Further analyses revealed that a Zuc in vivo cleavage preference at four sequences (UAA, UAG, UGA, UAC) promotes 5’ end stop codons. This observation was conserved across mammals and possibly further. Our work provides new insights into Zuc-dependent cleavage and may point to a previously unrecognized connection between piRNA biogenesis and the translational machinery.
A Riemannian approach to predicting brain function from the structural connectome
Authors: Benkarim Oualid , Paquola Casey , Park Bo-yong , Royer Jessica , Rodríguez-Cruces Raúl , de Wael Reinder Vos , Misic Bratislav , Piella Gemma , Bernhardt Boris C.
Published: October 2021

Abstract

Ongoing brain function is largely determined by the underlying wiring of the brain, but the specific rules governing this relationship remain unknown. Emerging literature has suggested that functional interactions between brain regions emerge from the structural connections through mono-as well as polysynaptic mechanisms. Here, we propose a novel approach based on diffusion maps and Riemannian optimization to emulate this dynamic mechanism in the form of random walks on the structural connectome and predict functional interactions as a weighted combination of these random walks. Our proposed approach was evaluated in two different cohorts of healthy adults (Human Connectome Project, HCP; Microstructure-Informed Connectomics, MICs). Our approach outperformed existing approaches and showed that performance plateaus approximately around the third random walk. At macroscale, we found that the largest number of walks was required in nodes of the default mode and frontoparietal networks, underscoring an increasing relevance of polysynaptic communication mechanisms in transmodal cortical networks compared to primary and unimodal systems.