bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantification of a Facility Radiological Security Risk Index With a Graphical User Interface Tool
Authors: Rane Shraddha , Harris Jason T.
Published: March 2022

Healthcare facilities around the world routinely use radioactive sources to diagnose and treat illness. To effectively manage the security of radioactive sources, these facilities need to understand the risk, which is comprised of threat, vulnerability, and consequences. The threat component of risk requires knowledge of potential adversaries and understanding their capabilities and intentions. To help articulate the multiple layers of threat and support better informed decisions, the research developed a risk-based methodology to evaluate radiological security at the facility level. The methodology is applied to a radiological dispersal device (RDD) incident from three radionuclides of concern: 137Cs, 60Co, and 192Ir. The results of the research have led to the creation of a potential facility risk index (PFRI). The PFRI is mathematically represented as the exponential product of the maximum expected utility among the threat groups, the sum of geographic vulnerability and cultural vulnerability, and net consequences. The PFRI is a novel risk index that quantifies the facility risk on a scale of 1 to 10, 1 being “very low risk” and 10 being “very high risk.” A MATLAB-based graphical user interface (GUI) tool was also developed to enable the radiological facility (i.e., healthcare facility) staff to conduct self-assessments and manage their most valuable assets. The PFRI methodology is a useful starting point for any healthcare facility risk assessment and is a valuable input for decision makers considering potential investments in security upgrades.
Discharges of Nuclear Medicine Radioisotopes: The Impact of an Abatement System
Authors: Barbosa Nathaly , Castillo Lorena Sandoval , Quimbayo Juan Sebastián
Published: March 2022

Clinical uses of radiopharmaceuticals imply the administration of radioactive substances that are mainly excreted through urine. The Nuclear Medicine Department at the Instituto Nacional de Cancerología (INC-COL) in Bogota, Colombia, administers radiopharmaceuticals for diagnostics and treatment to many patients, resulting in tens of cubic meters of radioactive waste water (WW) every day. As Colombian regulatory limits for liquid radioactive discharges to the sewer system are lower than in other countries, longer WW decay times are required, even when an in-house waste water treatment plant (WWTP) is used. To fulfill the requirements for controlled disposal of radioactive discharges, a complementary abatement system was implemented to retain WW for periods as long as 360 d, and was connected to the hospital´s WWTP. These holding times can cause major changes in the WW physicochemical parameters, reaching levels higher than acceptable. In this study, we evaluate the decontamination and decay efficiency of the retention system using water quality parameters and the amount of radioactivity in the effluents stored in the tanks and the WWTP. According to the results, to maintain the physicochemical parameters below acceptable levels, biological and chemical treatment of decayed WW is necessary before discharging it into urban waste water. Using the principles of dilution, retention, and decay, an integral radioactive WW management system was implemented favoring the quality of discharges and activity levels to the sewer system, with efficiencies close to 100% for WW from discharges in diagnostic procedures ranging from 98% (131I) to 100% (177Lu) for WW from discharges in therapeutic procedures. Activity concentration assessment in medically-derived radionuclides using an in-house waste water treatment plant (WWTP) and a complementary abatement system; an in-house WWTP could be used as an abatement system for short-lived radionuclides; and a tank-based abatement system attached to the in-house WWTP showed higher efficiencies for long-lived radionuclides and adequate physicochemical parameters for the discharge to the city sewage system.
Global Disability Trajectories Over the First Decade Following Combat Concussion
Authors: Mac Donald Christine L. , Barber Jason , Johnson Ann , Patterson Jana , Temkin Nancy
Published: March 2022

Objective:

To examine global disability trajectories in US military with and without traumatic brain injury (TBI) over the first decade following deployment to identify risk profiles for better intervention stratification, hopefully reducing long-term cost.

Setting:

Patients and participants were enrolled in combat or directly following medical evacuation at the time of injury and followed up every 6 months for 10 years.

Participants:

There are 4 main groups (n = 475), 2 primary and 2 exploratory: (1) combat-deployed controls without a history of blast exposure “non-blast- control” (n = 143), (2) concussive blast TBI “‘blast-TBI” (n = 236) (primary), (3) combat-deployed controls with a history of blast exposure “blast-control” (n = 54), and (4) patients sustaining a combat concussion not from blast “non-blast-TBI” (n = 42) (exploratory).

Design:

Prospective, observational, longitudinal study.

Main Measures:

Combat concussion, blast exposure, and subsequent head injury exposure over the first decade post-deployment. Global disability measured by the Glasgow Outcome Scale Extended (GOSE).

Results:

Latent class growth analysis identified 4 main trajectories of global outcome, with service members sustaining combat concussion 37 to 49 times more likely to be in the worse disability trajectories than non-blast-controls (blast-TBI: odds ratio [OR] = 49.33; CI, 19.77-123.11; P < .001; non-blast-TBI: OR = 37.50; CI, 10.01-140.50; P < .001). Even blast-exposed-controls were 5 times more likely to be in these worse disability categories compared with non-blast-controls (OR = 5.00; CI, 1.59-15.99; P = .007). Adjustment for demographic factors and subsequent head injury exposure did not substantially alter these odds ratios.

Conclusions:

Very high odds of poor long-term outcome trajectory were identified for those who sustained a concussion in combat, were younger at the time of injury, had lower education, and enlisted in the Army above the risk of deployment alone. These findings help identify a risk profile that could be used to target early intervention and screen for poor long-term outcome to aid in reducing the high public health cost and enhance the long-term quality of life for these service members following deployment.
Aspergillus Infection of the Thoracolumbar Vertebral Body in a Chronic Hepatitis B-Related Hepatocellular Carcinoma Patient: A Case Report
Authors: Liu Jing , Gao Yi-Dan , Jiang Yan-Ming , Wang Jie , Li Ge , Zhou Xiang , Zhu Qian-Ru , Chen Gong-Ying
Published: March 2022

This study reports a rare case of an Aspergillus infection of the thoracolumbar vertebral body in a chronic hepatitis B-related hepatocellular carcinoma patient. We report a hepatocellular carcinoma patient who presented with a 3-month history of lumbago after liver transcatheter arterial chemoembolization, and was finally diagnosed with a pulmonary and thoracolumbar vertebral body Aspergillus infection after diagnostic antifungal treatment for 1 year. This case suggests that diagnostic antifungal therapy is of great significance for patients with clinically suspected Aspergillus infections when it is difficult to obtain tissue specimens for determined diagnosis.
Clinical manifestation and current therapeutics in X-juvenile retinoschisis
Authors: Yang Yi-Ping , Jheng Ying-Chun , Chien Yueh , Tsai Ping-Hsing , Hwang De-Kuang , Weng Chang-Chi , Huang Yi-Ming , Hsu Chih-Chien , Chou Yu-Bai , Chen Shih-Jen , Lin Tai-Chi
Published: March 2022

X-linked juvenile retinoschisis (XLRS) is one of the common early-onset hereditary retinal degenerative diseases in men. The common symptoms of XLRS range from mild to severe central vision loss and radial stripes created by the fovea, the division of the inner layer of the retina in the peripheral retina and the significant decrease in b-wave amplitude (ERG). Retinoschisin, the 224-amino-acid protein product of the retinoschisis 1 (RS1) gene, contains a discoid domain as the primary structural unit, an N-terminal cleavable signal sequence, and an oligomerization-area component. Retinoschisin is a homo-octamer complex with disulfide links that are released by retinal cells. It helps preserve the retina’s integrity by binding to the surface of photoreceptors and bipolar cells. As a recessive genetic disease, XLRS was usually treated by prescribing low vision aids in most clinical cases. A gene replacement therapy based on adeno-associated virus vectors was initiated and showed a breakthrough in treating XLRS in 2014. Understanding the revolution of gene therapy for treating XLRS may accelerate its development and make this gene therapy the template for developing therapeutics against other inherited retinal diseases.
Parathyroidectomy for dialysis patients in the era of calcimimetics: The surgeons’ point of view
Authors: Lee Chen-Hsen , Chen Jui-Yu , Kuo Po-Chung , Chen Wei-Ting
Published: March 2022

Calcimimetics is a new drug for lowering serum parathyroid hormone (PTH), calcium and phosphate in patients with hyperparathyroidism (HPT) on long-term dialysis. It became available on market in 2006. The impact of calcimimetics on the treatment by parathyroidectomy (PTx) was reviewed from the surgeons’ point of view. Cure of renal HPT by calcimimetics is not feasible, but calcimimetics can improve preoperative cardiac ventricle ejection fractions by lowering serum PTH. Heart failure is not necessarily a contraindication for PTx. PTx should be done before irreversible organ damage occurs. Limb gangrenes is an ominous sign and should be prevented by frequent checkup for peripheral arterial circulation. The impact of renal osteodystrophy on the quality of life and as indirect cause of mortality deserves more attention in patients with renal HPT. Delayed referral to PTx leads to more complicated patients. A consensus between nephrologists and surgeons about propitious timing for PTx is necessary. Future prospect on the surgical treatment of renal HPT is proposed.

Supplemental figure; http://links.lww.com/ASAIO/A782
Clinical implications of mosaicism: a 10-year retrospective review of 83 families in a university-affiliated genetics clinic
Authors: Lee Mianne , Lui Adrian C.Y. , Mak Christopher C.Y. , Tsang Mandy H.Y. , Fung Jasmine L.F. , Yeung K.S. , Chung Brian Hon Yin
Published: March 2022

Mosaicism refers to the coexistence of two or more genetically distinct cell populations in an individual from a single fertilized egg. We performed a retrospective analysis of all patients diagnosed with mosaic disorders between 2010 and 2021 in a university-affiliated genetics clinic, which attends to territory-wide genetic consultations. All patients with confirmed mosaic diagnoses through reproductive (n = 6), prenatal (n = 24), and postnatal (n = 53) testing were examined. We observed that mosaic 45, X (n = 31) and PIK3CA-related overgrowth spectrum (n = 16) disorders were among the most prevalent diagnoses in the clinic, and the total percentage of patients with mosaicism in our cohort was 2.0% (83/4157). A review of the diagnostic journey highlights the challenge in diagnosing mosaic disorders, whereby 38% of the subjects required more than one test sample, and 52% of the cases required more than one orthogonal method of detection to reach the correct diagnosis. While detection of mosaicism is passive through routine clinical testing, for example karyotyping in reproductive and prenatal care, in postnatal care, clinicians can more actively drive the detection of mosaicism. Therefore, we recommend a low threshold for additional genetic testing in suspected mosaicism for more accurate diagnosis and counselling.
Novel approaches beyond standard immunofluorescence for kidney biopsies
Authors: Santoriello Dominick , Nasr Samih H.
Published: March 2022

Purpose of review

Immunofluorescence on frozen tissue (IF-F) utilizing antibodies against immunoglobulin (Ig) heavy and light chains (IgA, IgG and IgM, kappa and lambda) and components of classical and alternative complement pathways (C1q, C3c and C4) is the standard of renal pathology. However, conventional IF-F has limitations, particularly in nephropathies associated with organized and/or monoclonal Ig deposits. This review will discuss new applications of established methods beyond conventional IF-F and recent novel immunohistochemical methods.

Recent findings

The combined application of paraffin immunofluorescence (IF-P) and IgG subtype staining excluded monotypic deposits in 62–66% of DNA J homolog subfamily B member 9-associated fibrillary glomerulonephritis (FGN) with apparent monotypic deposits by IF-F, whereas IF-P unmasks IgG deposits in a subset of cases of immunotactoid glomerulopathy. A novel IF technique targeting epitopes at the junction of the Ig heavy and light chains was introduced and unmasked polytypic deposits in a subset of glomerulonephritis with apparent monotypic deposits on IF-F. A recent study described the successful application of co-detection by indexing (CODEX) multiplexed IF to visualize more than a dozen target antigens within a single kidney tissue section. Finally, immunohistochemical protocols for detection of the novel antigens in membranous nephropathy have already entered the clinical practice of renal pathology.

Novel ancillary techniques in renal pathology have the potential to significantly enhance our ability to evaluate renal biopsies.
The ‘ramp filter’ artifact in filtered back projection is due to attenuation not ramp filtering
Authors: Hansen Christopher L.
Published: March 2022

Background

Artifactually decreased counts in regions of the left ventricle adjacent to intense splanchnic activity have been described in single photon emission computed tomography imaging and attributed to the side lobes of ramp filtering, a crucial step in filtered back projection. However, filtered back projection is based on a mathematical proof that makes no assumptions about the distribution of activity implying there is another cause for this artifact.

Methods

Computer simulations of a left ventricle with varying intensity, proximity and size of adjacent splanchnic activity was created with and without attenuation. Both filtered back projection and an iterative expectation maximization algorithm were performed. Volume weighted bullseyes were generated then the ratio of average activity in regions in the anterior and inferior walls of the bullseye were calculated.

Results

In the absence of attenuation, there was no effect on uptake despite intense adjacent splanchnic activity. The effect of attenuation alone was mild but was greatly amplified by adjacent splanchnic uptake. This effect varied with the intensity, proximity and size of adjacent activity. Moving the attenuation to the apex of the left ventricle produced a paradoxical increase in counts to the inferior wall. The effect on iterative reconstruction was less pronounced than with filtered back projection and the paradoxical increase with attenuation at the apex did not occur.

Conclusion

The ramp filter artifact in single photon emission computed tomography reconstruction is due to attenuation, not ramp filtering per se. Adjacent splanchnic activity can result in either an increase or decrease in counts. These effects are less pronounced and more consistent with iterative reconstruction.
Role of p53 in regulation of hematopoiesis in health and disease
Authors: Barajas Sergio , Cai Wenjie , Liu Yan
Published: March 2022

Purpose of review

Human aging is associated with an exponential increase in the occurrence of clonal hematopoiesis of indeterminate potential (CHIP). CHIP is associated with increased risks of de novo and therapy-related hematologic neoplasms and serves as a reservoir for leukemic relapse. Somatic mutations in the TP53 gene, which encodes the tumor suppressor protein p53, rank in the top five among genes that were mutated in CHIP. TP53 mutations in CHIP are associated with an increased incidence of myeloid neoplasms such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). This review focuses on mechanisms by which mutant p53 promotes CHIP progression and drives the pathogenesis of MDS and AML. We will also discuss potential therapeutic approaches that can target mutant p53 and improve treatment outcomes of MDS and AML.

Recent findings

TP53 was frequently mutated in individuals with CHIP as well as in patients with MDS and AML. While clinical studies suggest that p53 mutant hematopoietic stem and progenitor cell expansion may predispose the elderly to hematologic neoplasms, the underlying mechanisms are not fully understood. Recent findings suggest that mutant p53 may utilize both cell autonomous and noncell autonomous mechanisms to promote CHIP development. Furthermore, we and others have demonstrated that several gain-of-function mutant p53 proteins have enhanced oncogenic potential beyond dominant-negative and loss-of-function effects. Notably, TP53 allelic state has important implications for genome stability, clinical presentation, and outcomes in MDS. Some small molecules reactivating wild-type p53 tumor suppressor activity show promising effects on some human MDS and AML cells with TP53 mutations in preclinical and early phases of clinical studies.

TP53 mutations in MDS and AML are correlated with advanced disease, poor prognosis, reduced overall survival, and dismal outcomes. Deep understanding of the functions of mutant p53 proteins is essential to devise effective therapies for patients with myeloid neoplasms and other human cancers with TP53 mutations. Targeting mutant p53 directly or pathways regulated by mutant p53 holds great potential in preventing CHIP progression and treating MDS and AML patients with TP53 mutations.
Macrophage SR-B1 in atherosclerotic cardiovascular disease
Authors: Huby Thierry , Le Goff Wilfried
Published: March 2022

Purpose of review

Scavenger receptor class B type 1 (SR-B1) promotes atheroprotection through its role in HDL metabolism and reverse cholesterol transport in the liver. However, evidence indicates that SR-B1 may impact atherosclerosis through nonhepatic mechanisms.

Recent findings

Recent studies have brought to light various mechanisms by which SR-B1 affects lesional macrophage function and protects against atherosclerosis. Efferocytosis is efficient in early atherosclerotic lesions. At this stage, and beyond its role in cholesterol efflux, SR-B1 promotes free cholesterol-induced apoptosis of macrophages through its control of apoptosis inhibitor of macrophage (AIM). At more advanced stages, macrophage SR-B1 binds and mediates the removal of apoptotic cells. SR-B1 also participates in the induction of autophagy which limits necrotic core formation and increases plaque stability.

These studies shed new light on the atheroprotective role of SR-B1 by emphasizing its essential contribution in macrophages during atherogenesis as a function of lesion stages. These new findings suggest that macrophage SR-B1 is a therapeutic target in cardiovascular disease.
Laser accessories: surgical fibers, strippers, cleavers, and protective glasses
Authors: Keller Etienne Xavier , Kronenberg Peter , Tailly Thomas , Corrales Mariela , Juliebø-Jones Patrick , Pietropaolo Amelia , Somani Bhaskar , De Coninck Vincent
Published: March 2022

Purpose of review

This review provides most recent findings and developments relating to surgical laser fibers, strippers, cleavers, and protective glasses.

Recent findings

The smallest core diameter that can be used with Holmium:YAG lasers is 200 μm. Smaller core diameter fibers can be used with the Thulium fiber laser and offer better flexibility and lower risk of fracture, at the risk of greater burnback effect. Misleading discrepancies between the true diameter of laser fibers and their packaging labels must be considered. Fiber tip degradation from the burnback occurs within few minutes, thus questioning the need for time-consuming fiber tip reprocessing with fiber strippers and special cleaving tools. This shortcoming also applies to instrument-protecting ball-tip fibers. Cleavage of fiber tips through their protective jackets (‘coated tips’) is a cheaper alternative for instrument protection, additionally offering better visual control of the fiber tip. Third-generation side-firing greenlight laser fibers are still prone to rapid deterioration. Laser eyewear does not seem necessary for Holmium:YAG applications, whereas laser-specific protective glasses should be worn for greenlight laser applications.

With better understanding of laser accessories, practicing urologists may tailor their practice to reach optimal efficacy and safety for Holmium:YAG, Thulium fiber laser and Greenlight laser applications.
Infant Formulas With Postbiotics
Authors: Szajewska Hania , Kołodziej Maciej , Skórka Agata , Pieścik‐Lech Małgorzata
Published: March 2022

Objectives:

Infant formulas (IF) with postbiotics, defined as inanimate microorganisms and/or their components that confer a health benefit on the host, are available. We systematically updated evidence on the safety and health effects of administering iF with postbiotics (with or without other modifications) compared with standard IF.

Methods:

The Cochrane Library, MEDLINE, and EMBASE databases were searched to December 2021.

Results:

Eleven randomized controlled trials were included. Using the Cochrane Risk of Bias Tool 2, for the primary outcomes, 5 trials had an overall high risk of bias, and 6 trials had some concerns of bias. Most data were available on IF fermented with Bifidobacterium breve C50 and Streptococcus thermophilus (BB/ST). These formulas, compared with the standard IF, were safe and well tolerated. Postbiotic formulas with additional modifications (ie, formula fermented with BB/ST & prebiotics, partly fermented formula with BB/ST and prebiotics with or without modified milk fat, partly fermented antiregurgitation formula with BB/ST and prebiotics) were generally safe and well tolerated but did not offer clear benefits replicated in other studies. Only limited data were available on formula fermented with Lactobacillus paracasei CBA L74.

Conclusions:

IF with postbiotics evaluated so far are safe and well tolerated by infants who cannot be breastfed. No firm conclusion can, however, be reached regarding the clinical effects and benefit of one formula over another. It seems reasonable to discuss with healthcare providers current evidence regarding specific modifications in infant formulas and let them decide whether the expected benefits meet expectations and are worth the cost.
Porto‐Sinusoidal Vascular Disease
Authors: Girard Chloé , Laborde Nolwenn , Marbach Clothilde , Mas Emmanuel , Bureau Christophe , Broué Pierre
Published: March 2022

Objectives:

Porto‐sinusoidal vascular disease (PSVD) refers to a broad spectrum of histological lesions and phenotypic expressions. There are only a few reported pediatric cases in the literature. The primary outcomes of this study were to describe the phenotype of children with PSVD, to specify their mode of presentation and their clinical, biological, histological, and radiological characteristics as well as to identify their underlying etiologies.

Methods:

This is a descriptive, retrospective, and monocentric study of children followed at our reference center for rare vascular liver diseases.

Results:

Our study included 30 children ages 2months to 17.4years at the time of diagnosis. in most cases, the diagnosis was made incidentally without manifestation of any clinical symptom but rather on the finding of splenomegaly on physical examination (n = 9) or biological abnormalities (n = 13). In the other cases, the main presenting symptom was an upper gastrointestinal bleeding (n = 6). At the first visit, liver laboratory values were either normal (37%) or slightly disturbed. Anemia and/or thrombocytopenia associated with hypersplenism were found in 60% of patients. Liver biopsy was necessary for diagnosis. A total of 80% of cases had no identified etiology. After a median follow‐up of 4.5 years, 33% had not developed portal hypertension (PHT) and we reported the first pediatric case of hepatocellular carcinoma in PSVD children.

Conclusions:

PSVD is responsible for nonspecific symptomatology with variable evolution sometimes marked by serious complications requiring invasive treatments or even liver transplantation. Regular monitoring is essential to prevent, detect, and treat complications.
Facial Reanimation Using Free Functional Muscle Transfer: Lessons Learnt From a Long Term Experience Comparing Innervation With Cross Facial Nerve Graft and Masseter Nerve
Authors: Kalra Gurdyal Singh , Kalra Sushrut , Gupta Samarth
Published: March 2022

Background:

Facial palsy is a complex problem and goal of reanimation is to achieve symmetric face at rest and spontaneous smile. in our study the authors performed facial reanimation in long standing cases of facial palsy (more than 1 year), gracilis muscle was used as a free functioning muscle transfer. Two motor donor nerves were used: cross-face nerve graft and masseter nerve.

Materials and Methods:

A total of 205 cases of unilateral facial reanimation with free functional muscle transfer (FFMT) were performed between 1998 and 2019. Out of 205 patients, 184 patients were operated by cross facial nerve graft-gracilis, and 21 by masseter nerve-gracilis. Quantitative assessment for outcome was done by measuring the excursion on follow up. Oral competence outcome and satisfaction score calculation was done by questionnaire. Results of spontaneous smile were divided into positive and negative groups.

Results:

A 2 stage cross facial nerve graft-gracilis FFMT achieved most natural and spontaneous smile when longer observation period (≥2 years) was followed. Masseter nerve-gracilis provided satisfactory results in the shortest rehabilitation period, had more excursion but never obtained spontaneous smile.

Conclusions:

The cross facial nerve graft-gracilis FFMT can achieve natural and spontaneous smile and remains our first choice for facial reanimation. Masseter nerve-gracilis can be used if cross facial nerve graft-gracilis fails, patient desires a single stage surgery and in some specific conditions, such as bilateral mobius syndrome.
The Impact of Virtual Surgical Planning on Orthognathic Surgery: Contributions From Two Specialties
Authors: Chen Jonlin , Abousy Mya , Girard Alisa , Duclos Olga , Patel Viren , Jenny Hillary , Redett Richard , Yang Robin
Published: March 2022

Background:

Virtual surgical planning (VSP) has gained popularity for preoperative orthognathic surgery planning and is increasingly being employed by surgeons trained in plastic and reconstructive surgery (PRS) or oral and maxillofacial surgery (OMS). This review assesses the introduction of VSP as a new technology and its impact on orthognathic surgery research and practices based upon surgeon training.

Methods:

Two PubMed literature reviews were conducted. The first classified publications on VSP for orthognathic surgery by training (OMS- or PRS-trained surgeons) and compared focuses, timing, and journals of publications from each group of surgeons. The second evaluated how orthognathic surgery publication volumes changed with VSP introduction. English articles published from inception until January 2020 (first review) and November 2020 (second review) were included.

Results:

The first literature review retrieved 419 unique publications, with 188 studies selected for inclusion: 162 were published by OMS-trained principal investigators (OMS-authored) and 26 by PRS-trained principal investigators (PRS-authored). Plastic and reconstructive surgery-authored publications regarding VSP use in orthognathic surgery increased after the first publication in 2000, but at a significantly slower rate (0.2 new publications/year) than OMS-authored publications (P < 0.01). Aesthetics was discussed in significantly more PRS-authored publications (76.9% compared to 28.4% of OMS-authored publications). The second review revealed that over 80.6% of orthognathic surgery literature was published after 2008, the year VSP was first integrated into orthognathic surgery workflow.

Conclusions:

Following the introduction of VSP, orthognathic surgery research output has differed between PRS and OMS based on publication speed, volume, and research focuses.

Further research is necessary to evaluate how VSP has impacted PRS and OMS clinical practice.
Efficacy and Complications of Mandibular Distraction Osteogenesis for Airway Obstruction in the Robin Sequence Population: A Comprehensive Literature Review
Authors: Chocron Yehuda , Barone Natasha , Zammit Dino , Gilardino Mirko S.
Published: March 2022

Introduction:

Mandibular distraction osteogenesis (MDO) is becoming the procedure of choice for patients with Robin Sequence (RS) as it offers superior long-term respiratory outcomes in avoidance of tracheostomy. Lacking, is an analysis of the short- and long-term complications. To that end, we have conducted a comprehensive review focusing on complications of MDO.

Materials and Methods:

A systematic review of primary clinical studies reporting outcomes and complications of MDO in RS patients. Outcomes included tracheostomy avoidance and decannulation rate. Complications included dental trauma, nerve injury, surgical site infection and hardware failure. Complications were stratified according to distractor type (internal versus external) and age (>2 months versus <2months).

Results:

A total of 49 studies yielded 1209 patients with a mean follow-up of 43.78 months. The tracheostomy avoidance rate was 94% (n = 817/870) and the mortality rate was 0.99% (n = 12/1209). The complication rate was 28.9% (n = 349/1209) with surgical site infections (10.5%) being most common. Dental and nerve injuries occurred in 7.9% and 3.2% of patients, respectively. Hardware replacement occurred in 1.2% of patients. internal distractors had higher rates of dental injury whereas external distractors had higher technical failure rates. There were no differences in complication rates (P
= 0.200), mortality (P = 0.94) or tracheostomy avoidance (P = 0.058) between patients >2months or <2months of age.

Conclusion:

Mandibular distraction osteogenesis is highly reliable and effective with a low mortality and high tracheostomy avoidance rate. There are important complications including nerve and dental injuries which require long-term follow-up. Neonatal patients do not appear to be at higher risk of complications reinforcing the safety of MDO in this population.
Software testing in microbial bioinformatics: a call to action
Authors: van der Putten Boas C.L. , Mendes C. I. , Talbot Brooke M. , de Korne-Elenbaas Jolinda , Mamede Rafael , Vila-Cerqueira Pedro , Coelho Luis Pedro , Gulvik Christopher A. , Katz Lee S. ,   The ASM NGS 2020 Hackathon participants
Published: March 2022

Computational algorithms have become an essential component of research, with great efforts by the scientific community to raise standards on development and distribution of code. Despite these efforts, sustainability and reproducibility are major issues since continued validation through software testing is still not a widely adopted practice. Here, we report seven recommendations that help researchers implement software testing in microbial bioinformatics. We have developed these recommendations based on our experience from a collaborative hackathon organised prior to the American Society for Microbiology Next Generation Sequencing (ASM NGS) 2020 conference. We also present a repository hosting examples and guidelines for testing, available from https://github.com/microbinfie-hackathon2020/CSIS.
Machine Learning Based Reanalysis of Clinical Scores for Distinguishing Between Ischemic and Hemorrhagic Stroke in Low Resource Setting
Authors: Bhardwaj Aman , Srivastava MV Padma , Vinny Pulikottil Wilson , Mehndiratta Amit , Vishnu Venugopalan Y , Garg Rahul
Published: March 2022

BACKGROUND

Identification of stroke and classifying them as ischemic and hemorrhagic type using clinical scores alone faces two unaddressed issues. One pertains to over-estimation of performance of scores and the other involves class imbalance nature of stroke data leading to biased accuracy. We conducted a quantitative comparison of existing scores, after correcting them for the above-stated issues. We explored the utility of Machine Learning theory to address overestimation of performance and class imbalance inherent in these clinical scores.

METHODS

We included validation studies of Siriraj (SS), Guys Hospital/Allen (GHS/AS), Greek (GS), and Besson (BS) Scores for stroke classification, from 2001-2021, identified from systematic search on PubMed, ERIC, ScienceDirect, and IEEE-Xplore. From included studies we extracted the reported cross tabulation to identify the listed issues. Further, we mitigated them while recalculating all the performance metrics for a comparative analysis of the performance of SS, GHS/AS, GS, and BS.

RESULTS

A total of 21 studies were included. Our calculated sensitivity range (IS-diagnosis) for SS is 40-90% (median 70%[IQR:57-73%], aggregate 71%[SD:15%]) as against reported 43-97% (78%[IQR:65-88%]), for GHS/AS 35-93% (64%[IQR:53-71%], 64%[SD:17%]) against 35-94% (73%[IQR:62-88%]), and for GS 60-74% (64%[IQR:62-69%], 69%[SD:7%]) against 74-94% (89%[IQR:81-92%]). Calculated sensitivity (HS-diagnosis), for SS, GHS/AS, and GS respectively, are 34-86% (59%[IQR:50-79%], 61%[SD:17%]), 20-73% (46%[IQR:34-64%], 44%[SD:17%]), and 11-80% (43%[IQR:27-62%], 51%[SD:35%]) against reported 50-95% (71%[IQR:64-82%]), 33-93% (63%[IQR:39-73%]), and 41-80% (78%[IQR:59-79%]). Calculated accuracy ranges, are 37-86% (67%[IQR:56-75%], 68%[SD:13%]), 40-87% (58%[IQR:47-61%], 59%[SD:14%]), and 38-76% (51%[IQR:45-63%], 61%[SD:19%]) while the weighted accuracy ranges are 37-85% (64%[IQR:54-73%], 66%[SD:12%]), 43-80% (53%[IQR:47-62%], 54%[SD:13%]), and 38-77% (51%[IQR:44-64%], 60%[SD:20%]). Only one study evaluated BS.

CONCLUSION

Quantitative comparison of existing scores indicated significantly lower ranges of performance metrics as compared to the ones reported by the studies. We conclude that published clinical scores for stroke classification over-estimate performance. We recommend inclusion of equivocal predictions while calculating performance metrics for such analysis. Further, the high variability in performance of clinical scores in stroke identification and classification could be improved upon by creating a global data-pool with statistically important attributes. Scores based on Machine Learning from such globally pooled data may perform better and generalise at scale.
Social connections at work and mental health during the first wave of the COVID-19 pandemic: Evidence from employees in Germany
Authors: Breetzke Jonas , Wild Eva-Maria
Published: March 2022

Empirical evidence on the social and psychological impact of the COVID-19 pandemic in the workplace and the resulting consequences for the mental health of employees is still sparse. As a result, research on this subject is urgently needed to develop appropriate countermeasures. This study builds on Person-Environment fit theory to investigate social connections at work and mental health during the first wave of the COVID-19 pandemic. It analyses employees’ needs for social connections and how social connections affect different mental health measures. Survey data were collected in May 2020 in an online survey of employees across Germany and analysed using response surface analysis. Mental health was measured as positive mental health and mental health disorders. Social connections were measured as social support and social interactions. 507 employees participated in the survey and more than one third reported having less social support and social interaction at work than they desired (p < .001). This was associated with a decrease in mental health. In contrast, having more than the desired amount of social support was associated with a decrease and having more than the desired amount of social interaction with an increase in mental health. This study provides important early evidence on the impact of the first wave of the COVID-19 pandemic in the workplace. With it, we aim to stimulate further research in the field and provide early evidence on potential mental health consequences of social distancing measures – while also opening avenues to combat them.
Oxylipin profiling identifies a mechanistic signature of metabolic syndrome: results from two independent cohorts
Authors: Dalle Céline , Tournayre Jérémy , Mainka Malwina , Basiak-Rasała Alicja , Pétéra Mélanie , Lefèvre-Arbogast Sophie , Dalloux-Chioccioli Jessica , Deschasaux-Tanguy Mélanie , Lécuyer Lucie , Kesse-Guyot Emmanuelle , Fezeu Léopold , Hercberg Serge , Galan Pilar , Samieri Cécilia , Zatońska Katarzyna , Calder Philip C. , Hjorth Mads Fiil , Astrup Arne , Mazur André , Bertrand-Michel Justine , Schebb Nils H. , Szuba Andrzej , Touvier Mathilde , Newman John W. , Gladine Cécile
Published: March 2022

Background

Metabolic syndrome (MetS) is a complex condition encompassing a constellation of cardiometabolic abnormalities. Integratively phenotyping the molecular pathways involved in MetS would help to deeply characterize its pathophysiology and to better stratify the risk of cardiometabolic diseases. Oxylipins are a superfamilly of lipid mediators regulating most biological processes involved in cardiometabolic health.

Methods

A high-throughput validated mass spectrometry method allowing the quantitative profiling of over 130 oxylipins was applied to identify and validate the oxylipin signature of MetS in two independent case/control studies involving 476 participants.

Results

We have uncovered and validated an oxylipin signature of MetS (coined OxyScore) including 23 oxylipins and having high performances of classification and replicability (cross-validated AUCROCof 89%, 95% CI: 85%-93% and 78%, 95% CI: 72%-85% in the Discovery and Replication studies, respectively). Correlation analysis and comparison with a classification model incorporating both the oxylipins and the MetS criteria showed that the oxylipin signature brings consistent and complementary information supporting its clinical utility. Moreover, the OxyScore provides a unique mechanistic signature of MetS regarding the activation and/or negative feedback regulation of crucial molecular pathways that may help identify patients at higher risk of cardiometabolic diseases.

Conclusion

Oxylipin profiling identifies a mechanistic signature of metabolic syndrome that may help to enhance MetS phenotyping and ultimately to better predict the risk of cardiometabolic diseasesviaa better patient stratification.
A versatile Halo- and SNAP-tagged BMP/TGFβ receptor library for quantification of cell surface ligand binding
Authors: Jatzlau Jerome , Burdzinski Wiktor , Trumpp Michael , Obendorf Leon , Roßmann Kilian , Ravn Katharina , Hyvönen Marko , Bottanelli Francesca , Broichhagen Johannes , Knaus Petra
Published: March 2022

The TGFβ superfamily of secreted growth factors comprises more than 30 members including TGFβs, BMPs and Activins. While all TGFβ superfamily members signal through heteromeric receptor complexes to regulate a plethora of developmental and homeostatic processes, each ligand possesses a unique affinity towards a subset of BMP and TGFβ type I and type II receptors. Whereas the Activin and TGFβ class display a higher affinity towards type II receptors, BMPs and GDFs preferentially bind to type I receptors. Sofar, the lack of specific antibodies and chemical biology tools hampered simultaneous testing of ligand binding towards all BMP and TGFβ receptors. Here we present a N-terminally Halo- and SNAP-tagged TGFβ/BMP receptor library to visualize the receptor complexes in dual color. In combination with novel fluorescently labeled TGFβ superfamily ligands, we established a Ligand Surface Binding Assay (LSBA) for optical quantification of receptor-dependent growth factor binding for Activin A, TGFβ1 and BMP9 in a cellular context. We confirm ligand-receptor interface specificity by identifying BMPR2- or ALK2-mutants that switch from a low-affinity Activin A- or BMP9-receptor to a high-affinity receptor, respectively.
The ion permeability of DNA nanotube channels
Authors: Dhanasekar Naresh Niranjan , Li Yi , Schulman Rebecca
Published: March 2022

Techniques from structural DNA nanotechnology make it possible to assemble complex 3-dimensional nanostructures with virtually arbitrary control over their sizes, shapes and features at length scales of 3–100 nm, providing a flexible means for constructing nanoscale devices and machines. Here, we assemble micron-length DNA nanotubes and assess their performance as pipes for controlled ion transport. DNA nanotubes growviaassembly of DNA tiles from a seed pore, a 12-helix DNA origami cylinder functionalized with cholesterol, to form a DNA nanotube channel. The central channel of a nanotube can be obstructed via Watson-Crick hybridization of a channel cap, a second DNA origami structure, to the end of a nanotube channel or a nanotube seed pore. Single-channel electrophysiological characterization shows that both nanotube seed pores and nanotube channels display ohmic ion conductance consistent with their central channels’ diameters. Binding of the channel cap reduces the conductances of both DNA nanotube channels and seed pores, demonstrating control of ion-transport through these micron-length channels. Because these channels could be assembled into branched architectures or routed between specific molecular terminals, these results suggest a route to self-assembling nanofluidic devices and circuits in which transport can be controlled using dynamic biomolecular interactions.
Activated I-BAR IRSp53 clustering controls the formation of VASP-actin-based membrane protrusions
Authors: Tsai Feng-Ching , Henderson J. Michael , Jarin Zack , Kremneva Elena , Senju Yosuke , Pernier Julien , Mikhajlov Oleg , Manzi John , Kogan Konstantin , Le Clainche Christophe , Voth Gregory A. , Lappalainen Pekka , Bassereau Patricia
Published: March 2022

Filopodia are actin-rich membrane protrusions essential for cell morphogenesis, motility, and cancer invasion. How cells control filopodia initiation on the plasma membrane remains elusive. We performed experiments in cellulo, in vitro and in silico to unravel the mechanism of filopodia initiation driven by the membrane curvature sensor IRSp53. We showed that full-length IRSp53 self-assembles into clusters on membranes depending on PIP2. Using well-controlled in vitro reconstitution systems, we demonstrated that IRSp53 clusters recruit the actin polymerase VASP to assemble actin filaments locally on membranes, leading to the generation of actin-filled membrane protrusions reminiscent of filopodia. By pulling membrane nanotubes from live cells, we observed that IRSp53 can only be enriched and trigger actin assembly in nanotubes at highly dynamic membrane regions. Our work supports a regulation mechanism of IRSp53 in its attributes of curvature sensation and partner recruitment to ensure a precise spatial-temporal control of filopodia initiation.
Stimulus-dependent depth constancy during head tilt
Authors: Skerswetat Jan , Caoli Andrea , Bex Peter
Published: March 2022

Stereopsis is traditionally measured with noise-based stereo tests while the observer views the test in primary gaze. We investigated the effect of stimulus sparseness and axial variations of interocular disparity induced via head rotations.

First, we measured stereoacuity using a 4-Alternative-Forced-Choice (4-AFC) task with three uncrossed and one crossed disparity bandpass-filtered circles on a passive-3-D-monitor. Ten binocularly-normal adults fixated a central cross and clicked on the circle withcrossed disparity for forty trials/condition. Observers adopted head tilts of 0° or ±20° pitch, roll, or yaw, enforced with an innertial measurement unit and fixation enforced with an eye tracker. Next, we measured stereoacuity in 8 adults while either the head (H), monitor (M), or both (B) were tilted 0°, ±22.5°, or ±45° roll in random order (eighty trials/condition) using a 4-AFC task and random-dot stimuli. Head tilts did not signifcantly alter stereoacuity using narrow-band stimuli(p>0.05), despite that IPDs and the axis of disparity were differentially affected by the tilts. However, for random dot stimuli, stereoacuity decreased with increasing orientation difference between the head and monitor (H and M: p<0.05; B: p>0.05].

Head tilt decreases IPD and rotates the axis of interocular disparity, however, these manipulations affect stereoacuity when measured with noise stimuli but not with sparse stimuli. The results are consistent with a vestibular input to stereoscopic disparity processing that can be detected by sparse stimuli but is masked by dense stimuli. The results have implications for natural vision and for clinical screening in patients with abnormal head posture.

Significance statement

Depth perception is a critical feature of human vision and it is thought that the ability to perceive stereoscopic depth is bound to an essentially eye-fixed, horizontal disparity of each image that rapidly deteriorates away from that limited horizontal axis. In a set of head tilt experiments, we varied the orientations of stereoscopic images and demonstrate that stereoacuity remains constant when deploying sparse narrow-band stimuli, and only worsens when using fine-detailed noise stimuli that mask off-axis disparities. These results shine new light upon the debate of neuroplasticity of stereo vision. Moreover, the results are consequential for diagnosis and treatment in people with atypical head- and eye alignment, such as for patients with torticollis or strabismus.