bluuebunny/crossref_metadata_2025 huggingface dataset:
Lean Principles to Improve Quality in High-Throughput COVID-19 Testing Using SwabSeq: A Barcoded Sequencing-Based Testing Platform
Authors: Jones Janae , Saul Rosita , Sathe Laila , Xie Joanna , Marquette Dawn , Arboleda Valerie A
Published: July 2021

Objective

To describe and quantify the effect of quality control (QC) metrics to increase testing efficiency in a high-complexity, Clinical Laboratory Improvement Amendments–certified laboratory that uses amplicon-based, next generation sequencing for the clinical detection of SARS-CoV-2. To enable rapid scalability to several thousands of specimens per day without fully automated platforms, we developed internal QC methods to ensure high-accuracy testing.

Methods

We implemented procedures to increase efficiency by applying the Lean Six Sigma model into our sequencing-based COVID-19 detection.

Results

The application of the Lean Six Sigma model increased laboratory efficiency by reducing errors, allowing for a higher testing volume to be met with minimal staffing. Furthermore, these improvements resulted in an improved turnaround time.

Conclusion

Lean Six Sigma model execution has increased laboratory efficiency by decreasing critical testing errors and has prepared the laboratory for future scaling up to 50,000 tests per day.
Plasma microlensing dynamic spectrum probing fine structures in the ionized interstellar medium
Authors: Shi Xun , Xu Zhu
Published: July 2021

Gravitational microlensing has become a mature technique for discovering small gravitational lenses in the Universe that are otherwise beyond our detection limits. Similarly, plasma microlensing can help us explore cosmic plasma lenses. Both pulsar scintillation and extreme scattering events of compact radio sources suggest the existence of ∼au-scale plasma lenses in the ionized interstellar medium (IISM), whose astrophysical correspondence remains a mystery. We demonstrate that plasma microlensing events by these plasma lenses recorded in the form of wide-band dynamic spectra are a powerful probe of their nature. Using the recently developed Picard–Lefschetz integrator for the Kirchhoff–Fresnel integral, we simulate such dynamic spectra for a well-motivated family of single-variable plasma lenses. We demonstrate that the size, strength, and shape of the plasma lens can be measured from the location of the cusp point and the shape of spectral caustics, respectively, with a combination of distances and the effective velocity known a priori or measured from the widths of the interference pattern. Future wide-band observations of pulsars, whose plasma microlensing events may be predictable from parabolic arc monitoring, are the most promising ground to apply our results for a deeper insight into the fine structures in the IISM.
AI-assisted superresolution cosmological simulations – II. Halo substructures, velocities, and higher order statistics
Authors: Ni Yueying , Li Yin , Lachance Patrick , Croft Rupert A C , Di Matteo Tiziana , Bird Simeon , Feng Yu
Published: July 2021

In this work, we expand and test the capabilities of our recently developed superresolution (SR) model to generate high-resolution (HR) realizations of the full phase-space matter distribution, including both displacement and velocity, from computationally cheap low-resolution (LR) cosmological N-body simulations. The SR model enhances the simulation resolution by generating 512 times more tracer particles, extending into the deeply nonlinear regime where complex structure formation processes take place. We validate the SR model by deploying the model in 10 test simulations of box size 100 h−1 Mpc, and examine the matter power spectra, bispectra, and two-dimensional power spectra in redshift space. We find the generated SR field matches the true HR result at per cent level down to scales of k ∼ 10 h  Mpc−1. We also identify and inspect dark matter haloes and their substructures. Our SR model generates visually authentic small-scale structures that cannot be resolved by the LR input, and are in good statistical agreement with the real HR results. The SR model performs satisfactorily on the halo occupation distribution, halo correlations in both real and redshift space, and the pairwise velocity distribution, matching the HR results with comparable scatter, thus demonstrating its potential in making mock halo catalogues. The SR technique can be a powerful and promising tool for modelling small-scale galaxy formation physics in large cosmological volumes.
X-ray observations of two candidate symbiotic binaries in the galactic bulge
Authors: Wetuski Joshua , Hynes R I , Maccarone T J , Heinke C , Torres M A P , Jonker P G , Britt Christopher T , Steeghs D , Nelemans G
Published: July 2021

This paper analyses X-ray observations by the Chandra X-ray Observatory of CXOGBS J174614.3−321949 (CXB3) and CXOGBS J173620.2−293338 (CX332), two symbiotic binary star candidates identified by the Galactic Bulge Survey. Using new Chandra observations, we improved their X-ray positional uncertainties to 0.24 and 0.92 arcsec, respectively, confidently associating them with single optical counterparts. In particular, new observations of symbiotic X-ray candidate CX332 further solidify confidence in its coincidence with a carbon star. We demonstrate X-ray variability in both targets with a more recent observation of CX332 showing a decrease in brightness by a factor of 30, while CXB3 observations show it usually in a quiescent state with a factor-of-6 flare-like event in the final observations. In a combined spectral fit for CXB3, we find an NH value of $\sim (2\!-\! 3) \times 10^{22}\, \rm {cm}^{-2}$ with a Γ value of $1.5^{+0.2}_{-0.2}$ for a power-law fit and kT$10.6_{-2.9}^{+5.7}$ keV for an apec fit and an estimated luminosity of ∼8.4 × 1032 erg s−1. Spectra of CXB3 would be consistent with thermal emission as seen in white dwarf symbiotic systems, but the high X-ray luminosity in the light curve is more typically seen in symbiotic X-ray binary systems. Optical spectra of both objects taken with Gemini GMOS indicate CXB3 as containing an M-type star and CX332 having a carbon star counterpart. Both targets show at most marginal evidence of H α emission favouring a symbiotic X-ray binary interpretation for both sources, though we cannot rule out a white dwarf for either case.
Selective blood-brain barrier permeabilization of brain metastases by a type 1 receptor-selective tumor necrosis factor mutein
Authors: Munoz Pinto Mario F , Campbell Sandra J , Simoglou Karali Christina , Johanssen Vanessa A , Bristow Claire , Cheng Vinton W T , Zarghami Niloufar , Larkin James R , Pannell Maria , Hearn Arron , Chui Cherry , Brinquis Nunez Barbara , Bokma Evert , Holgate Robert , Anthony Daniel C , Sibson Nicola R
Published: July 2021

Background

Metastasis to the brain is a major challenge with poor prognosis. The blood-brain barrier (BBB) is a significant impediment to effective treatment, being intact during the early stages of tumor development and heterogeneously permeable at later stages. Intravenous injection of tumor necrosis factor (TNF) selectively induces BBB permeabilization at sites of brain micrometastasis, in a TNF type 1 receptor (TNFR1)-dependent manner. Here, to enable clinical translation, we have developed a TNFR1-selective agonist variant of human TNF that induces BBB permeabilization, while minimizing potential toxicity.

Methods

A library of human TNF muteins (mutTNF) was generated and assessed for binding specificity to mouse and human TNFR1/2, endothelial permeabilizing activity in vitro, potential immunogenicity, and circulatory half-life. The permeabilizing ability of the most promising variant was assessed in vivo in a model of brain metastasis.

Results

The primary mutTNF variant showed similar affinity for human TNFR1 than wild-type human TNF, similar affinity for mouse TNFR1 as wild-type mouse TNF, undetectable binding to human/mouse TNFR2, low potential immunogenicity, and permeabilization of an endothelial monolayer. Circulatory half-life was similar to mouse/human TNF and BBB permeabilization was induced selectively at sites of micrometastases in vivo, with a time window of ≥24 hours and enabling delivery of agents within a therapeutically relevant range (0.5-150 kDa), including the clinically approved therapy, trastuzumab.

Conclusions

We have developed a clinically translatable mutTNF that selectively opens the BBB at micrometastatic sites, while leaving the rest of the cerebrovasculature intact. This approach will open a window for brain metastasis treatment that currently does not exist.
Impaired Timing of Speech-Related Neurons in the Subthalamic Nucleus of Parkinson Disease Patients Suffering Speech Disorders
Authors: Tankus Ariel , Lustig Yael , Fried Itzhak , Strauss Ido
Published: July 2021

BACKGROUND

Our previous study found degradation to subthalamic neuronal encoding of speech features in Parkinson disease (PD) patients suffering from speech disorders.

OBJECTIVE

To find how timing of speech-related neuronal firing changes in PD patients with speech disorders compared to PD patients without speech disorders.

METHODS

During the implantation of deep brain stimulator (DBS), we recorded the activity of single neurons in the subthalamic nucleus (STN) of 18 neurosurgical patients with PD while they articulated, listened to, or imagined articulation of 5 vowel sounds, each following a beep. We compared subthalamic activity of PD patients with (n = 10) vs without speech disorders.

RESULTS

In this comparison, patients with speech disorders had longer reaction times and shorter lengths of articulation. Their speech-related neuronal activity preceding speech onset (planning) was delayed relative to the beep, but the time between this activity and the emission of speech sound was similar. Notwithstanding, speech-related neuronal activity following the onset of speech (feedback) was delayed when computed relative to the onset. Only in these patients was the time lag of planning neurons significantly correlated with the reaction time. Neuronal activity in patients with speech disorders was delayed during imagined articulation of vowel sounds but earlier during speech perception.

CONCLUSION

Our findings indicate that longer reaction times in patients with speech disorders are due to STN or earlier activity of the speech control network. This is a first step in locating the source(s) of PD delays within this network and is therefore of utmost importance for future treatment of speech disorders.
Complete resolution of a giant multilocular prostatic cystadenoma following androgen deprivation therapy: an illustrative case report
Authors: Sushentsev Nikita , Rimmer Yvonne , Barrett Tristan
Published: July 2021

Giant multilocular prostatic cystadenoma (GMPC) is a rare benign pelvic mass for which complete surgical resection is an accepted treatment of choice. This report presents the first case of complete resolution of GMPC following a 3-year course of luteinising hormone-releasing hormone agonist alongside external beam radiotherapy for the concurrent treatment of unfavorable intermediate-risk prostate cancer. In addition to illustrating the imaging features of the effect of androgen deprivation therapy (ADT) and radiotherapy on GMPC regression, this case provides evidence for considering ADT as an alternative, noninvasive GMPC treatment option in patients in whom surgical treatment is either contraindicated or can be made less invasive by reducing the size of GMPC prior to its removal.
Recycling of the major thylakoid lipid MGDG and its role in lipid homeostasis in Chlamydomonas reinhardtii
Authors: Iwai Masako , Yamada-Oshima Yui , Asami Kota , Kanamori Takashi , Yuasa Hideya , Shimojima Mie , Ohta Hiroyuki
Published: July 2021

Monogalactosyldiacylglycerol (MGDG), the most abundant lipid in thylakoid membranes, is involved in photosynthesis and chloroplast development. MGDG lipase has an important role in lipid remodeling in Chlamydomonas reinhardtii. However, the process related to turnover of the lysogalactolipid that results from MGDG degradation, monogalactosylmonoacylglycerol (MGMG), remains to be clarified. Here we identified a homolog of Arabidopsis thaliana lysophosphatidylcholine acyltransferase (LPCAT) and characterized two independent knockdown (KD) alleles in C. reinhardtii. The enzyme designated as C. reinhardtiiLysolipid Acyltransferase 1 (CrLAT1) has a conserved membrane-bound O-acyl transferase domain. LPCAT from Arabidopsis has a key role in deacylation of phosphatidylcholine (PC). Chlamydomonas reinhardtii, however, lacks PC, and thus we hypothesized that CrLAT1 has some other important function in major lipid flow in this organism. In the CrLAT1 KD mutants, the amount of MGMG was increased, but triacylglycerols (TAGs) were decreased. The proportion of more saturated 18:1 (9) MGDG was lower in the KD mutants than in their parental strain, CC-4533. In contrast, the proportion of MGMG has decreased in the CrLAT1 overexpression (OE) mutants, and the proportion of 18:1 (9) MGDG was higher in the OE mutants than in the empty vector control cells. Thus, CrLAT1 is involved in the recycling of MGDG in the chloroplast and maintains lipid homeostasis in C. reinhardtii.
A genetic approach reveals different modes of action of prefoldins
Authors: Blanco-Touriñán Noel , Esteve-Bruna David , Serrano-Mislata Antonio , Esquinas-Ariza Rosa María , Resentini Francesca , Forment Javier , Carrasco-López Cristian , Novella-Rausell Claudio , Palacios-Abella Alberto , Carrasco Pedro , Salinas Julio , Blázquez Miguel Á , Alabadí David
Published: July 2021

The prefoldin complex (PFDc) was identified in humans as a co-chaperone of the cytosolic chaperonin T-COMPLEX PROTEIN RING COMPLEX (TRiC)/CHAPERONIN CONTAINING TCP-1 (CCT). PFDc is conserved in eukaryotes and is composed of subunits PFD1–6, and PFDc-TRiC/CCT folds actin and tubulins. PFDs also participate in a wide range of cellular processes, both in the cytoplasm and in the nucleus, and their malfunction causes developmental alterations and disease in animals and altered growth and environmental responses in yeast and plants. Genetic analyses in yeast indicate that not all of their functions require the canonical complex. The lack of systematic genetic analyses in plants and animals, however, makes it difficult to discern whether PFDs participate in a process as the canonical complex or in alternative configurations, which is necessary to understand their mode of action. To tackle this question, and on the premise that the canonical complex cannot be formed if one subunit is missing, we generated an Arabidopsis (Arabidopsis thaliana) mutant deficient in the six PFDs and compared various growth and environmental responses with those of the individual mutants. In this way, we demonstrate that the PFDc is required for seed germination, to delay flowering, or to respond to high salt stress or low temperature, whereas at least two PFDs redundantly attenuate the response to osmotic stress. A coexpression analysis of differentially expressed genes in the sextuple mutant identified several transcription factors, including ABA INSENSITIVE 5 (ABI5) and PHYTOCHROME-INTERACTING FACTOR 4, acting downstream of PFDs. Furthermore, the transcriptomic analysis allowed assigning additional roles for PFDs, for instance, in response to higher temperature.
Mitochondrial carbonic anhydrases are needed for optimal photosynthesis at low CO2 levels in Chlamydomonas
Authors: Rai Ashwani K , Chen Timothy , Moroney James V
Published: July 2021

Chlamydomonas reinhardtii can grow photosynthetically using CO2 or in the dark using acetate as the carbon source. In the light in air, the CO2 concentrating mechanism (CCM) of C. reinhardtii accumulates CO2, enhancing photosynthesis. A combination of carbonic anhydrases (CAs) and bicarbonate transporters in the CCM of C. reinhardtii increases the CO2 concentration at Ribulose 1,5-bisphosphate carboxylase oxygenase (Rubisco) in the chloroplast pyrenoid. Previously, CAs important to the CCM have been found in the periplasmic space, surrounding the pyrenoid and inside the thylakoid lumen. Two almost identical mitochondrial CAs, CAH4 and CAH5, are also highly expressed when the CCM is made, but their role in the CCM is not understood. Here, we adopted an RNAi approach to reduce the expression of CAH4 and CAH5 to study their possible physiological functions. RNAi mutants with low expression of CAH4 and CAH5 had impaired rates of photosynthesis under ambient levels of CO2 (0.04% CO2 [v/v] in air). These strains were not able to grow at very low CO2 (<0.02% CO2 [v/v] in air), and their ability to accumulate inorganic carbon (Ci = CO2 + HCO3−) was reduced. At low CO2 concentrations, the CCM is needed to both deliver Ci to Rubisco and to minimize the leak of CO2 generated by respiration and photorespiration. We hypothesize that CAH4 and CAH5 in the mitochondria convert the CO2 released from respiration and photorespiration as well as the CO2 leaked from the chloroplast to HCO3- thus “recapturing” this potentially lost CO2.
Efficacy and Safety of Awake Computed Tomography–Guided Percutaneous Balloon Compression of Trigeminal Ganglion for Trigeminal Neuralgia
Authors: Huang Bing , Yao Ming , Chen QiLiang , Du Xindan , Li Zhang , Xie Keyue , Fei Yong , Do Huy , Qian Xiang
Published: July 2021

Objectives

To describe the method and clinical efficacy of awake computed tomography (CT)–guided percutaneous balloon compression (PBC) as a treatment for trigeminal neuralgia (TN).

Design

In this case series, patients with TN were treated with awake CT-guided PBC and followed up for treatment efficacy and complications for 12 months.

Setting

A single-center study.

Subjects

A total of 66 patients with medical treatment–refractory TN were recruited for the study.

Methods

The procedure was performed under moderate sedation. A balloon catheter was inserted through a trocar needle to reach Meckel’s cavity under CT guidance. The position and optimal shape of the contrast-filled balloon were confirmed with CT three-dimensional reconstruction. Compression of the trigeminal ganglion was considered complete when the patient notified operators about facial hypoesthesia or the resolution of TN symptoms. All patients were followed up monthly for 12 months to monitor treatment efficacy and complications.

Results

The average trigeminal ganglion compression time was 272 ± 81 seconds, at which point the patients reported significant facial hypoesthesia compared with the contralateral side or resolution of triggered pain in the affected area. All patients had resolution of TN symptoms for 6 months, with a 1-year recurrence rate of 13%. The overall safety profile was improved with the technique described in this study. Side effects, such as hypoesthesia and mastication weakness, were overall mild and did not impact patients’ quality of life. Some complications that historically have been associated with PBC, such as diplopia and keratitis, were not present.

Conclusions

This new awake CT-guided PBC technique produces better outcomes than the traditional PBC under fluoroscopy guidance and general anesthesia.
Making personalized medicine ethical: a critical examination of the new promises of ‘personalized health’ in Switzerland
Authors: Barazzetti Gaia , Bühler Nolwenn , Audétat Marc , Kaufmann Alain
Published: July 2021

This article explores how promises are forged in the emerging techno-scientific field of ‘personalized health’ (PH) in Switzerland and how they challenge the research-healthcare boundary when dealing with issues of ethical acceptability. Switzerland provides a relevant location in which to examine these questions as PH has emerged in this context with the specific connotation of improving health in the population as a whole, through the development of a data infrastructure to enable nationwide accessibility and sharing of health-related data. Drawing on our analyses of discourses and practices of scientific and institutional actors, we show that the development of PH in Switzerland is the result of ethical boundary work aimed at enrolling local biomedical institutions, heterogeneous groups of professionals, as well as the general public in nationwide research initiatives with important implications for healthcare and the healthcare system.
Predictors of COVID-19 vaccine intentions in the United States: the role of psychosocial health constructs and demographic factors
Authors: Berg Michael B , Lin Linda
Published: July 2021

Background

On December 21, 2020, a study was conducted to investigate a range of psychosocial health constructs and demographic variables potentially associated with intentions toward accepting or forgoing the coronavirus (COVID-19) vaccine.

Purpose

The goal of the study was to identify predictors of forgoing COVID-19 vaccination at the time of the initial rollout.

Methods

A cross-sectional, representative online survey of 350 U.S. residents was conducted using the online crowdsourcing site Prolific to assess vaccine intentions, health attitudes, and demographic information. Variables examined included demographic factors and health constructs corresponding to each of the elements of the health belief model (perceived severity, susceptibility, benefits, barriers, and cues to action), the theory of planned behavior (attitudes, subjective norms, and perceived behavioral control), attitudes toward vaccines in general, and trust in the COVID-19 vaccine approval process.

Results

After using hierarchical linear regression to control for demographics, the health constructs uniquely associated with the likelihood to forgo vaccination were perceived barriers, general attitudes toward the COVID-19 vaccine, subjective norms, and trust in the vaccine approval process. Significant demographic predictors of vaccine reluctance included being female, politically conservative, and more religious.

Conclusions

The current research identified three demographic factors and four health constructs uniquely associated with vaccine acceptance. These findings reveal that the constructs contained within the health belief model and theory of planned behavior can be used to predict COVID-19 vaccination intentions, and can be supplemented with an assessment of general vaccine attitudes and attitudes toward the vaccine approval process.
Diplodia Leaf Streak of Corn: A Diagnostic Guide
Authors: Anderson Nolan R. , Bradley Carl A. , Wise Kiersten A.
Published: July 2021

The official common name of the foliar disease on corn is Diplodia leaf streak, often given the shorthand nomenclature DLS. The only known host of DLS is corn (Zea mays). The fungus that causes DLS is Stenocarpella macrospora (syn. Diplodia macrospora). DLS symptoms can be confused with several common foliar diseases of corn. This guide details symptoms and signs, as well as pathogen identification.
Improving Common Bacterial Blight Phenotyping by Using Rub Inoculation and Machine Learning: Cheaper, Better, Faster, Stronger
Authors: Foucher Justine , Ruh Mylène , Briand Martial , Préveaux Anne , Barbazange Florian , Boureau Tristan , Jacques Marie-Agnès , Chen Nicolas W. G.
Published: July 2021

Accurate assessment of plant symptoms plays a key role for measuring the impact of pathogens during plant−pathogen interaction. Common bacterial blight caused by Xanthomonas phaseoli pv. phaseoli and X. citri pv. fuscans is a major threat to common bean. The pathogenicity of these bacteria is variable among strains and depends mainly on a type III secretion system and associated type III effectors such as transcription activator-like effectors. Because the impact of a single gene is often small and difficult to detect, a discriminating methodology is required to distinguish the slight phenotype changes induced during the progression of the disease. Here, we compared two different inoculation and symptom assessment methods for their ability to distinguish two tal mutants from their corresponding wild-type strains. Interestingly, rub inoculation of the first leaves combined with symptom assessment by machine learning-based imaging allowed significant distinction between wild-type and mutant strains. By contrast, dip inoculation of first-trifoliate leaves combined with chlorophyll fluorescence imaging did not differentiate the strains. Furthermore, the new method developed here led to the miniaturization of pathogenicity tests and significant time savings.
Insights into the Cell-to-Cell Signaling and Iron Homeostasis in Xanthomonas Virulence and Lifestyle
Authors: Pandey Sheo Shankar , Chatterjee Subhadeep
Published: July 2021

The Xanthomonas group of phytopathogens causes economically important diseases that lead to severe yield loss in major crops. Some Xanthomonas species are known to have an epiphytic and in planta lifestyle that is coordinated by several virulence-associated functions, cell-to-cell signaling (using diffusible signaling factor [DSF]), and environmental conditions, including iron availability. In this review, we described the role of cell-to-cell signaling by the DSF molecule and iron in the regulation of virulence-associated functions. Although DSF and iron are involved in the regulation of several virulence-associated functions, members of the Xanthomonas group of plant pathogens exhibit atypical patterns of regulation. Atypical patterns contribute to the adaptation to different lifestyles. Studies on DSF and iron biology indicate that virulence-associated functions can be regulated in completely contrasting fashions by the same signaling system in closely related xanthomonads.
Pathotype Complexity and Genetic Characterization ofPhytophthora sojaePopulations in Illinois, Indiana, Kentucky, and Ohio
Authors: Hebb Linda M. , Bradley Carl A. , Mideros Santiago Xavier , Telenko Darcy E. P. , Wise Kiersten , Dorrance Anne E.
Published: July 2021

Phytophthora sojae, the causal agent of Phytophthora root and stem rot of soybean, has been managed with single Rps genes since the 1960s but has subsequently adapted to many of these resistance genes, rendering them ineffective. The objective of this study was to examine the pathotype and genetic diversity of P. sojae from soil samples across Illinois, Indiana, Kentucky, and Ohio by assessing which Rps genes were still effective and identifying possible population clusters. There were 218 pathotypes identified from 473 P. sojae isolates with an average of 6.7 out of 15 differential soybean lines exhibiting a susceptible response for each isolate. Genetic characterization of 103 P. sojae isolates from across Illinois, Indiana, Kentucky, and Ohio with 19 simple sequence repeat markers identified 92 multilocus genotypes. There was a moderate level of population differentiation between these four states, with pairwise FSTvalues ranging from 0.026 to 0.246. There were also moderate to high levels of differentiation between fields, with pairwise FSTvalues ranging from 0.071 to 0.537. Additionally, cluster analysis detected the presence of P. sojae population structure across neighboring states. The level of pathotype and genetic diversity, in addition to the identification of population clusters, supports the hypothesis of occasional outcrossing events that allow an increase in diversity and the potential to select for a loss in avirulence to specific resistance genes within regions. The trend of suspected gene flow among neighboring fields is expected to be an ongoing issue with current agricultural practices.
Anesthesia for deep brain stimulation: an update
Authors: Dinsmore Michael , Venkatraghavan Lashmi
Published: July 2021

Purpose of review

Deep brain stimulation (DBS) is a rapidly expanding surgical modality for the treatment of patients with movement disorders. Its ability to be adjusted, titrated, and optimized over time has given it a significant advantage over traditional more invasive surgical procedures. Therefore, the success and popularity of this procedure have led to the discovery of new indications and therapeutic targets as well as advances in surgical techniques. The aim of this review is to highlight the important updates in DBS surgery and to exam the anesthesiologist's role in providing optimal clinical management.

Recent findings

New therapeutic indications have a significant implication on perioperative anesthesia management. In addition, new technologies like frameless stereotaxy and intraoperative magnetic resonance imaging to guide electrode placement have altered the need for intraoperative neurophysiological monitoring and hence increased the use of general anesthesia. With an expanding number of patients undergoing DBS implantation, patients with preexisting DBS increasingly require anesthesia for unrelated surgery and the anesthesiologist must be aware of the considerations for perioperative management of these devices and potential complications.

DBS will continue to grow and evolve requiring adaptation and modification to the anesthetic management of these patients.
An Exploration of Blood Marker×Environment Interaction Effects on Pain Severity and Interference Scores in People With Acute Musculoskeletal Trauma
Authors: Lee Joshua Y. , Fakhereddin Mohamad , MacDermid Joy C. , Elliott James M. , Schabrun Siobhan M. , Walton David M.
Published: July 2021

Objectives:

Explore the moderating effects of psychological or social variables on associations between biomarkers of inflammation/stress and clinical reports of pain.

Methods:

This is a cross-sectional exploratory study. Data were drawn from the Systematic Merging of Biology, Mental Health and Environment (SYMBIOME) longitudinal study (clinicaltrials.gov ID no. NCT02711085). Eligible participants were adults who presented to an Urgent Care Centre in Ontario, Canada within 3 weeks of a noncatastrophic musculoskeletal trauma (no surgery or hospitalization). A questionnaire package was given that included the Brief Pain Inventory (capturing pain severity and pain interference) and relevant person-level variables. Blood samples were also drawn for serum analysis of 8 target biomarkers (brain-derived neurotrophic factor, transforming growth factor beta 1 [TGF-β1], c-reactive protein, tumor necrosis factor-α, interleukin [IL]-1β, IL-6, IL-10, and cortisol).

Results:

Employment before trauma (employed for pay/not employed for pay) fully moderated the association between tumor necrosis factor-α and pain severity (∆R2=4.4%). Pre-existing psychopathology (yes/no) fully moderated the association between TGF-β1 and pain severity (∆R2=8.0%). Sex (male/female) fully moderated the association between c-reactive protein and pain severity (∆R2=6.3%). A pre-existing pain condition (yes/no) was significantly associated with worse pain interference (R2=7.2%), and partially moderated the effect of IL-1β on pain interference (∆R2=6.9%). Higher peritraumatic life stress significantly explained 8.9% of variance in pain interference alone, and partially moderated the effect of TGF-β1 on interference (∆R2=4.4%).

Discussion:

Simple bivariate associations between blood-based markers and clinical symptoms are unlikely to reveal meaningful relationships. However, when stratified by existing person-level or “metadata” variables, an association may exist for at least 1 clinically relevant subgroup.
Same Day Surgical Intervention Dramatically Minimizes Complication Occurrence and Optimizes Perioperative Outcomes for Central Cord Syndrome
Authors: Bortz Cole , Dinizo Michael , Kummer Nicholas , Brown Avery , Alas Haddy , Pierce Katherine E. , Janjua Muhammad B. , Park Paul , Wang Charles , Jankowski Pawel , Hockley Aaron , Soroceanu Alex , De la Garza Ramos Rafael , Sciubba Daniel M. , Frempong-Boadu Anthony , Vasquez-Montes Dennis , Diebo Bassel G. , Gerling Michael C. , Passias Peter G.
Published: July 2021

Study Design:

This was a retrospective cohort study.

Objective:

The aim of this study was to investigate associations between time to surgical intervention and outcomes for central cord syndrome (CCS) patients.

Background:

As surgery is increasingly recommended for patients with neurological deterioration CCS, it is important to investigate the relationship between time to surgery and outcomes.

Materials and Methods:

CCS patients were isolated in Nationwide Inpatient Sample database 2005−2013. Patients were grouped by time to surgery: same-day, 1-day delay, 2, 3, 4−7, 8−14, and >14 days. Means comparison tests compared patient factors, perioperative complications, and charges across patient groups. Controlling for age, comorbidities, length of stay, and concurrent traumatic fractures, binary logistic regression assessed surgical timing associated with increased odds of perioperative complication, using same-day as reference group.

Results:

Included: 6734 CSS patients (64% underwent surgery). The most common injury mechanisms were falls (30%) and pedestrian accidents (7%). Of patients that underwent surgery, 52% underwent fusion, 30% discectomy, and 14% other decompression of the spinal canal. Breakdown by time to procedure was: 39% same-day, 16% 1-day, 10% 2 days, 8% 3 days, 16% 4−7 days, 8% 8−14 days, and 3% >14 days. Timing groups did not differ in trauma status at admission, although age varied: [minimum: 1 d (58±15 y), maximum: >14 d (63±13 y)]. Relative to other groups, same-day patients had the lowest hospital charges, highest rates of home discharge, and second lowest postoperative length of stay behind 2-day delay patients. Patients delayed >14 days to surgery had increased odds of perioperative cardiac and infection complications. Timing groups beyond 3 days showed increased odds of VTE and nonhome discharge.

Conclusions:

CCS patients undergoing surgery on the same day as admission had lower odds of complication, hospital charges, and higher rates of home discharge than patients that experienced a delay to operation. Patients delayed >14 days to surgery were associated with inferior outcomes, including increased odds of cardiac complication and infection.
Interventions to Improve Trainers' Learning and Behaviors for Educating Health Care Professionals Using Train-the-Trainer Method: A Systematic Review and Meta-analysis
Authors: Poitras Marie-Eve , Bélanger Emilie , Vaillancourt Vanessa T. , Kienlin Simone , Körner Mirjam , Godbout Isabelle , Bernard-Hamel Joelle , O'Connor Sarah , Blanchette Patricia , Khadhraoui Lobna , Sawadogo Jasmine , Massougbodji José , Zomahoun Hervé Tchala Vignon , Gallani Maria-Cecilia , Stacey Dawn , Légaré France
Published: July 2021

Introduction:

Train-the-trainer (TTT) programs are frequently used to facilitate knowledge dissemination. However, little is known about the effectiveness of these programs. Therefore, we sought to assess the impact of TTT programs on learning and behavior of trainers for educating health and social professionals (trainees).

Methods:

Guided by the Cochrane Effective Practice and Organisation of Care, we conducted a systematic review. We searched 12 databases until April 2018 and extracted data according to the Population, Intervention, Comparison, Outcome model. Population was defined as trainers delivering training program to health care professionals, and the intervention consists in any organized activity provided by a trainer. There were no restrictive comparators, and outcomes were knowledge, attitude, skill, confidence, commitment, and behavior of trainers. We estimated the pooled effect size and its 95% confidence interval using a random-effect model. We performed a narrative synthesis when meta-analysis was not possible.

Results:

Of 11,202 potentially eligible references, we identified 16 unique studies. Studies were mostly controlled before-and-after studies and covered a unique training intervention. Targeted trainers were mostly nurses (n = 10) and physicians (n = 5). The most frequent measured outcome was knowledge (n = 12). TTT programs demonstrated significant effect on knowledge (Standardized mean deviation = 0.58; 95% CI = 0.11–1.06; I2 = 90%; P < .01; 10 studies). No studies measured trainers' ability to deliver the training program.

Discussion:

TTT programs may improve the knowledge of trainers. However, the heterogeneity and small number of studies hamper our ability to draw conclusions that are more robust.
T-Regulatory Cells in Erythema Nodosum Leprosum: An Immunohistochemical and Image Morphometric Study
Authors: Biswas Dipanwita , Sethy Madhusmita , Behera Biswanath , Palit Aparna , Mitra Suvradeep
Published: July 2021

Erythema nodosum leprosum (ENL) occurs as an immune-inflammatory complication of multibacillary leprosy (MBL), precipitated by an interaction between the host, bacilli, and the environment. This complication often causes significant morbidity due to systemic involvement and needs to be treated aggressively. T-regulatory cells (T-regs) are the immunomodulatory subset of T cells that are hypothesized to play a role in ENL. We have performed immunohistochemistry for FoxP3 (T-reg), CD3 (pan-T), CD4 (helper T), and CD8 (cytotoxic T) on 50 biopsy-proven cases of ENL along with 84 biopsy-proven cases of paucibacillary leprosy (PBL) (n = 49) and MBL (n = 35). Image morphometry was applied to objectively assess the relative preponderance of these subsets of T cells. The area fraction of T-regs showed a trend of reduction from PBL to MBL to ENL (P = 0.068), whereas the FoxP3:CD3 (T-reg: pan-T) ratio showed a significant reduction across these groups (P = 0.023). However, there was no significant difference of T-regs or FoxP3:CD3 ratio between MBL and ENL. The T-regs showed a significant positive correlation (P = 0.007) with the cytotoxic T cells in the skin biopsy. The presence of dermal eosinophils in ENL showed a trend association with the FoxP3:CD3 ratio (P = 0.05). Various histopathological parameters including epidermal spongiosis, dermal stromal edema, dermal ill-formed granuloma, and the presence of bacilli within the endothelium and vascular smooth muscle correlated with various T-cell subsets. Our study, one of the largest on this topic, objectively assessed the role of T-regs in the spectrum of leprosy. Nevertheless, the precipitation of ENL from MBL is probably not associated with the T-reg subset alone.
Population Pharmacokinetics of Infliximab in Children with Juvenile Idiopathic Arthritis
Authors: Nassar-Sheikh Rashid Amara , Schonenberg-Meinema Dieneke , Berends Sophie E. , van den Berg J. Merlijn , Mathôt Ron A.A.
Published: July 2021

Background:

The recommended infliximab (IFX) dose in (pediatric) rheumatology practice is 3–6 mg/kg every 4–8 weeks. Higher dosage regimens (>10 mg/kg) of IFX are effective and safe. To optimize IFX treatment in patients with juvenile idiopathic arthritis (JIA), therapeutic drug monitoring might be beneficial. To support routine therapeutic drug monitoring of IFX and regimen optimization for patients with JIA, in-depth knowledge of the pharmacokinetic (PK) variability of IFX is needed. As soon as the optimal therapeutic drug ranges are known, PK model–based simulation can be used to individualize drug dosing recommendations. In this study, a population PK model for IFX is described for patients with JIA.

Methods:

Data including IFX trough concentrations and anti-IFX antibodies of 27 pediatric patients with JIA on IFX maintenance treatment were retrieved from electronic charts. Three population PK models from the literature were validated for the authors' data set using the nonlinear mixed-effects modeling program NONMEM. A novel population PK model was developed based on the study data.

Results:

A total of 65 blood samples obtained after a median of 32 days after the last IFX infusion (interquartile range 28–42) were analyzed. The 3 published models underpredicted the observed trough concentrations. A newly developed one-compartment model best described the data corresponding to IFX serum concentration over time in patients with JIA.

Conclusions:

This study shows a novel PK model for IFX in patients with JIA. The data show that different PK models are needed for different age categories (children or adults) and different diseases.
Post-Breast Surgery Pain Syndrome: Shifting a Surgical Paradigm
Authors: Beederman Maureen , Bank Jonathan
Published: July 2021

Post-mastectomy pain syndrome and the less well-described post-breast surgery pain syndrome are long-term neuropathic pain conditions that may affect more than 50% of patients after mastectomy and breast surgery. While the etiology, risk factors, and management have been reviewed in our literature, we offer here a focused outline that will gear the plastic surgeon with tools to lead a multidisciplinary, algorithmic approach to the care of patients with post-mastectomy pain syndrome/post-breast surgery pain syndrome. After reading this article, we hope the reader will have improved awareness of post-mastectomy pain syndrome/post-breast surgery pain syndrome, and thus be able to incorporate appropriate treatments and preventative steps into their primary surgical routine.
RETINAL TOXICITY FOLLOWING PRESUMED INADVERTENT INTRAOCULAR INJECTION OF MITOMYCIN C DURING TRABECULECTOMY
Authors: Desai Ria , Jampol Lee M.
Published: July 2021

Purpose:

To describe a case of postoperative retinal toxicity following the use of mitomycin C during a routine trabeculectomy.

Methods:

Case report of a single patient who underwent complete ophthalmic examination and multimodal imaging, including color fundus photos, optical coherence tomography, fundus autofluorescence, and fluorescein angiography. The study was declared exempt by the Institutional Review Board of Northwestern University. This research followed the tenets of the Declaration of Helsinki.

Results:

The patient developed profound vision loss and retinal damage during the postoperative course. Posterior segment findings include loss of vascular perfusion, diffuse loss of the outer, then inner, retinal layers, and subsequent total retinal detachment.

Conclusion:

Although mitomycin C is commonly used in glaucoma filtering surgeries, reports of postoperative posterior segment toxicity are rare. The etiology of postoperative toxicity in this case is probable inadvertent intraocular injection of mitomycin C.
Retrobulbar Hyaluronidase Injection: Does It Reach the Eye?
Authors: Rudraprasad Dhanwini , Gagan Satyashree , Joseph Joveeta , Vasanthapuram Varshitha Hemanth , Naik Milind N.
Published: July 2021

Purpose:

To determine if retrobulbar injection of hyaluronidase reaches the vitreous cavity, and to determine its concentration in the vitreous.

Methods:

Prospective case-control study. Patients undergoing evisceration with implant for noninfective blind eyes were enrolled in the study. Before the evisceration, a retrobulbar injection of 3,000 IU of hyaluronidase (2 ml) was injected. Time from injection to in vivo sampling of posterior vitreous was noted. Vitreous samples from controls were obtained from patients undergoing vitrectomy for retinal detachment or diabetic retinopathy. Concentration of hyaluronidase was assessed in all 30 samples. An ELISA-based microtiter-technique was used to evaluate the activity of hyaluronidase by an avidin-peroxidase-based procedure using an ELISA reader. Incubations were carried out at room temperature and at 37°C. All the samples were analyzed in duplicates, and the mean of each sample was plotted on a scatter plot.

Results:

Total of 30 vitreous samples were analyzed, of which 15 were controls and 15 were test samples. Of the 15 test samples, injection-to-sampling time was 0 to 20 minutes in 4 samples, 20 to 40 minutes in 6 samples, and 40 to 60 minutes in 5 samples. The highest concentration of hyaluronidase detected in control and test samples were 2.9 and 3.0 µg/ml, and the lowest concentration was 1.7 and 1.5 µg/ml (SD 0.3), respectively. There was no significant difference between control and test groups.

Conclusion:

Retrobulbar injection did not result in higher concentration of hyaluronidase in the posterior vitreous compared with controls when measured up to 60 minutes following injection.
The Management of Orbital Roof Fractures and Defects: A Review
Authors: Sandhu Pavandeep Singh , Bucur Sorin , Good Catriona , Cutler Mark , Rajak Saul
Published: July 2021

Purpose:

To explore the anatomy, etiopathogenesis, diagnosis and classification, current evidence on intervention and the surgical management of orbital roof fractures and defects (ORFD) for oculoplastic surgeons presented with such cases.

Methods:

A review of the current literature through the MEDLINE database using the following search terms: “orbital roof fracture (+treatment/management),” “orbital roof defect (+treatment/management),” “orbital roof erosion (+treatment/management),” “orbital roof repair,” “orbital roof,” “orbital fracture,” “pediatric orbital roof (defect/fracture/erosion),” “orbital anatomy,” and “orbital roof anatomy” was conducted. As relatively little has been published on this topic, inclusion criteria were broad and peer-reviewed articles judged to be of clinical importance, relevant to the aims of this review, were included. Non-English abstracts were also included if relevant. Year of publication was not a strict exclusion criterion, and older articles were judged for their suitability based on clinical importance and relevance to current practice. Additional references were obtained from citations in key articles and recommendations from the coauthors based on their areas of expertise.

Results:

The etiopathogenesis of ORFD varies. Classification systems have been formulated to guide management decisions and can range from conservative management to complex neurosurgery. Eyelid approaches have also been described. This review provides a summary of the evidence for each and a management framework oculoplastic surgeons can use when presented with ORFD.

Conclusion:

Oculoplastic surgeons can be involved, either alone or as part of a multidisciplinary team, in the management of ORFD, and for some, conduct orbital approach reconstructive surgery.
Tocilizumab for the Management of Thyroid-Associated Orbitopathy
Authors: Smith Loreley D. , Moscato Eve E. , Seiff Stuart R.
Published: July 2021

Purpose:

To describe the efficacy of tocilizumab in the treatment of a cohort of patients with active thyroid-associated orbitopathy.

Methods:

Patients were identified with active thyroid-associated orbitopathy who were intolerant of or had progression of disease despite systemic corticosteroids and subsequently were treated with tocilizumab between January 2015 and December 2020. Clinical Activity Score, Thyroid-Associated Ophthalmopathy Scale score, and thyroid-stimulating immunoglobulin levels were assessed prior to initiation of tocilizumab, following the first dose, and after the completion of treatment.

Results:

Eleven patients were candidates for and underwent treatment with tocilizumab, 9 of which met criteria for analysis. Average age was 55.6 years. Average time between onset of active thyroid-associated orbitopathy and completion of tocilizumab was 6.5 months. Average number of infusions was 4.2. There was a statistically significant reduction in Clinical Activity Score, Thyroid-Associated Ophthalmopathy Scale score, and thyroid-stimulating immunoglobulin levels when comparing pre-treatment values (mean Clinical Activity Score 6.78 ± 1.09, mean Thyroid-Associated Ophthalmopathy Scale score 10.2 ± 1.92, mean thyroid-stimulating immunoglobulin level 440.6 [%]) to values immediately following completion of treatment (mean Clinical Activity Score 0.44 ± 0.53, mean difference 6.3 points, p < 0.001 [95% CI, 5.5–7.2]; mean Thyroid-Associated Ophthalmopathy Scale score 1.2 ± 1.09, mean difference 9.0 points, p < 0.001 [95% CI, 7.2–10.8]; mean thyroid-stimulating immunoglobulin level 200.7 [%], mean difference 239.9 [%], p = 0.001 [95% CI, 124.3–355.4]). One patient had elevation of cholesterol following therapy induction. Patients were followed for an average of 23.6 months after treatment. No patients had recurrence of active disease after completion of tocilizumab.

Conclusions:

This study supports the use of tocilizumab as a therapy for the inflammatory phase of thyroid-associated orbitopathy.