bluuebunny/crossref_metadata_2025 huggingface dataset:
Back from Burnout
Authors: Sefton Marlene
Published: November 2022

Healthy and supportive engagement between faculty and students is imperative for positive learning experiences. Multiple factors can impede engagement, including faculty burnout. After 30 years of teaching nursing, the author faced burnout. Based on student comments and Scripture, suggestions are made about character and teaching attributes that can positively adjust educator attitudes to enhance student learning.
Effect of Rim-Off Deep Lateral Orbital Decompression on Interpalpebral Fissure Shape
Authors: Equitério Bruna , Garcia Denny , Galindo-Ferreiro Alicia , Marqués-Fernández Victoria , Sales-Sanz Marco , Cruz Antonio Augusto Velasco
Published: November 2022

Purpose:

The purpose of this study is to compare the palpebral fissure shape after rim-off deep lateral decompression with and without restoration of the lateral orbital rim.

Methods:

Retrospective cross-sectional quantitative analysis of the palpebral fissure images of 17 patients (25 eyes) who underwent rim-off deep lateral orbital decompression without repositioning of the rim (G1) and of 20 patients (34 eyes) operated with rim restoration. Quantification of palpebral fissure images included MRD1 and MRD2, two lateral mid-pupil lid margin (MPD) distances, the width of the palpebral fissure, and the height and shape of the lateral canthus.

Results:

Proptosis reduction did not differ significantly between G1 and G2. In both groups, decompression reduced the mean values of the MRD1 and MRD2, the lateral height of the upper eyelid, and the height and angle of the lateral canthus. The palpebral fissure width and lateral height of the lateral lower eyelid were not affected. There was no significant difference between the mean changes of G1 and G2. Multivariate analysis showed that the lateral canthus decrease was correlated with changes in MRD1 and MRD2.

Conclusions:

Small changes in palpebral fissure shape after deep lateral decompression are not dependent on the presence or absence of the lateral rim.
Sebaceous Carcinoma of the Eyelid: Proposed Nomenclature for Multifocal and Multicentric Disease
Authors: Magazin Maja , Dalvin Lauren A. , Salomao Diva R. , Castner Nicholas B. , Halbach Caroline , Tooley Andrea A.
Published: November 2022

Purpose:

To review clinical presentations of periocular sebaceous carcinoma (SC) and introduce standardized nomenclature for multicentric and multifocal disease presentation.

Methods:

A comprehensive PubMed/Medline search was conducted to identify all articles reporting periocular multicentric or multifocal SC presentations. The authors also highlight an additional case of SC presenting with 2 clinically distinct tumor foci and complete secondary invasion of the lacrimal gland.

Results:

This review summarizes clinical presentations of periocular SC exhibiting discrete foci of microinvasion reported in the literature. Discrete microinvasion was associated with high rates of misdiagnosis (80%), simultaneous involvement of both upper and lower eyelids (80%), pagetoid spread (80%), multinodular growth (33%), local tumor spread (60%), previous eyelid manipulation (40%), and local recurrence (40%). Eyelid multifocality with clinically discrete nodules (42%) was associated with more advanced disease including orbital extension and regional invasion (80%).

Conclusions:

Despite previous reported associations with poorer outcomes, there is no consensus in the definition or nomenclature for discrete microinvasive or clinical disease presentations in periocular SC. The authors recommend defining multicentric disease as discrete foci of microinvasive tumor with basement membrane disruption and multifocal disease as discrete clinically evident nodules involving both the upper and lower eyelids. Differentiating between discrete microinvasive (multicentric) and clinically nodular (multifocal) disease may improve risk stratification to most accurately identify patients who require more aggressive management and surveillance.
Aneurysmal Bone Cyst of the Orbit With USP6 Gene Rearrangement
Authors: Phan Tracey , Tong Jessica , Krivanek Michael , Graf Nicole , Dexter Mark , Tumuluri Krishna
Published: November 2022

Purpose:

Aneurysmal bone cyst (ABC) of the orbit is a very rare tumor, occurring mostly in the pediatric population, and can result in sight threatening complications and disfigurement. This review discusses previously reported cases with a focus on evolving treatment options and molecular genetics.

Methods:

We report the youngest case of an orbital ABC with a confirmed gene fusion: a 17-month-old girl, with confirmed FGFR-UPS6 (Fibroblast Growth Factor Receptor 1-ubiquitin specific peptidase 6/tre-2). A literature search for relevant publications on the topic was performed via Medline and PubMed, with the appropriate data extracted.

Results:

Thirty-two cases of orbital aneurysmal bone cyst were identified in the literature. Presentations are varied and can include pain, proptosis, decreased vision, and extraocular motility disturbance. Typical imaging and histopathology findings are discussed, in particular the usefulness of identifying USP6 gene arrangements. Treatment modalities are reviewed including surgery, embolization, and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors. Recurrences can occur, usually within 2 years.

Conclusions:

Orbital ABC is a neoplasm that presents unique diagnostic and treatment challenges. Gene rearrangements can confirm primary ABC and rule out other underlying pathology. Disfigurement and sight threatening complications can occur due to both the disease process and with treatment. Outcomes may be improved with the use of systemic therapy.
Structural brain connectivity predicts early acute pain after mild traumatic brain injury
Authors: Branco Paulo , Bosak Noam , Bielefeld Jannis , Cong Olivia , Granovsky Yelena , Kahn Itamar , Yarnitsky David , Apkarian A. Vania
Published: November 2022

Mild traumatic brain injury (mTBI), is a leading cause of disability worldwide, with acute pain manifesting as one of its most debilitating symptoms. Understanding acute postinjury pain is important because it is a strong predictor of long-term outcomes. In this study, we imaged the brains of 157 patients with mTBI, following a motorized vehicle collision. We extracted white matter structural connectivity networks and used a machine learning approach to predict acute pain. Stronger white matter tracts within the sensorimotor, thalamiccortical, and default-mode systems predicted 20% of the variance in pain severity within 72 hours of the injury. This result generalized in 2 independent groups: 39 mTBI patients and 13 mTBI patients without whiplash symptoms. White matter measures collected at 6 months after the collision still predicted mTBI pain at that timepoint (n = 36). These white matter connections were associated with 2 nociceptive psychophysical outcomes tested at a remote body site—namely, conditioned pain modulation and magnitude of suprathreshold pain—and with pain sensitivity questionnaire scores. Our findings demonstrate a stable white matter network, the properties of which determine an important amount of pain experienced after acute injury, pinpointing a circuitry engaged in the transformation and amplification of nociceptive inputs to pain perception.
Heparin Versus Bivalirudin for Anticoagulation in Adult Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis
Authors: Wieruszewski Patrick M. , Macielak Shea A. , Nei Scott D. , Moman Rajat N. , Seelhammer Troy G. , Nabzdyk Christoph G. S. , Gerberi Danielle J. , Mara Kristin C. , Hooten W. Michael , Wittwer Erica D.
Published: November 2022

Extracorporeal membrane oxygenation (ECMO) poses unique thrombotic and hemorrhagic risks, and the optimal anticoagulant choice is unknown. We systematically searched Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science Core Collection for randomized-, crossover-, retrospective cohort-, or parallel-designed clinical studies of adult patients receiving ECMO that compared heparin recipients with bivalirudin recipients. Meta-analysis was performed with random-effects models. The ROBINS-I tool was used to assess the risk of bias. Six retrospective observational studies met the inclusion criteria for the qualitative summary. Five studies were suitable for meta-analysis. Those who received heparin were more likely to experience circuit-related thrombosis (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.25–3.37, p = 0.005, I
2 = 0%) and die (OR 1.62, 95% CI 1.19–2.21, p = 0.002, I
2 = 0%) compared with those who received bivalirudin. There were no differences in major bleeding events between heparin and bivalirudin recipients (OR 1.83, 95% CI 0.55–6.09, p = 0.33, I
2 = 82.7%). In retrospective settings compared with heparin anticoagulation, bivalirudin was associated with less circuit-related thrombotic events and greater survival in adults supported on ECMO, without contributing to more bleeding complications. Prospective controlled studies comparing heparin and bivalirudin in adult ECMO patients are warranted to corroborate these findings.
Association of Medicare Advantage Star Ratings With Racial and Ethnic Disparities in Hospitalizations for Ambulatory Care Sensitive Conditions
Authors: Park Sungchul , Werner Rachel M. , Coe Norma B.
Published: November 2022

Background:

Enrollment in high-quality Medicare Advantage (MA) plans, measured by a 5-star quality rating system, was lower among racial and ethnic minority enrollees than White enrollees partly due to fewer high-quality plans available in their counties of residence. This may contribute to racial and ethnic disparities in ambulatory care sensitive condition (ACSC) hospitalizations.

Objective:

We examined whether there were racial and ethnic disparities in ACSC hospitalizations among MA enrollees overall and by star rating.

Methods:

Using the Medicare enrollment and claims data for 2016, we identified White, Black, Hispanic, and Asian/Pacific Islander enrollees in MA plans. We estimated racial and ethnic disparities in ACSC hospitalizations (per 10,000 enrollees) overall and by star rating.

Results:

We found that the adjusted rates of ACSC hospitalizations were significantly higher among Black enrollees than White enrollees overall [39.4 (95% confidence interval: 36.3–42.5)]. However, no significant disparities were found among Hispanic and Asian/Pacific Islander enrollees. The adjusted rates of ACSC hospitalizations were higher in lower-rated plans than higher-rated plans in all racial and ethnic groups. The significant disparities in ACSC hospitalizations by star rating were the most pronounced between White and Black enrollees. We found suggestive evidence that enrollment in lower-rated plans was associated with higher disparities in ACSC hospitalizations between White and Black enrollees.

Conclusions:

Substantial disparities in ACSC hospitalizations exist between White and Black enrollees in MA plans, especially for lower-rated plans. Policies aimed at reducing racial disparities in ACSC hospitalizations could include improving access to high-rated plans.
Inherited bone marrow failure syndromes: a review of current practices and potential future research directions
Authors: Deng Joseph , McReynolds Lisa J.
Published: November 2022

Purpose of review

Recent advances in diagnosis and treatment of inherited bone marrow failure syndromes (IBMFS) have significantly improved disease understanding and patient outcomes. Still, IBMFS present clinical challenges that require further progress. This review aims to provide an overview of the current state of diagnosis and treatment modalities of the major IBMFS seen in paediatrics and present areas of prioritization for future research.

Recent findings

Haematopoietic cell transplantation (HCT) for IBMFS has greatly improved in recent years, shifting the research and clinical focus towards cancer predispositions and adverse effects of treatment. Each year, additional novel genes and pathogenic variants are described, and genotype-phenotype mapping becomes more sophisticated. Moreover, novel therapeutics exploring disease-specific mechanisms show promise to complement HCT and treat patients who cannot undergo current treatment options.

Research on IBMFS should have short-term and long-term goals. Immediate challenges include solidifying diagnostic and treatment guidelines, cancer detection and treatment, and continued optimization of HCT. Long-term goals should emphasize genotype-phenotype mapping, genetic screening tools and gene-targeted therapy.
Advances in robotics and pediatric spine surgery
Authors: Cirrincione Peter , Widmann Roger F. , Heyer Jessica H.
Published: November 2022

Purpose of review

Robotic-assisted surgical navigation for placement of pedicle screws is one of the most recent technological advancements in spine surgery. Excellent accuracy and reliability results have been documented in the adult population, but adoption of robotic surgical navigation is uncommon in pediatric spinal deformity surgery. Pediatric spinal anatomy and the specific pediatric pathologies present unique challenges to adoption of robotic assisted spinal deformity workflows. The purpose of this article is to review the safety, accuracy and learning curve data for pediatric robotic-assisted surgical navigation as well as to identify “best use” cases and technical tips.

Recent findings

Robotic navigation has been demonstrated as a safe, accurate and reliable method to place pedicle screws in pediatric patients with a moderate learning curve. There are no prospective studies comparing robotically assisted pedicle screw placement with other techniques for screw placement, however several recent studies in the pediatric literature have demonstrated high accuracy and safety as well as high reliability. In addition to placement of pediatric pedicle screws in the thoracic and lumbar spine, successful and safe placement of screws in the pelvis and sacrum have also been reported with reported advantages over other techniques in the setting of high-grade spondylolisthesis as well as pelvic fixation utilizing S2-alar iliac (S2AI) screws.

Early studies have demonstrated that robotically assisted surgical navigation for pedicle screws and pelvic fixation for S2AI screws is safe, accurate, and reliable in the pediatric population with a moderate learning curve.
Liver transplantation and intrahepatic cholangiocarcinoma: time to go forward again?
Authors: Kodali Sudha , Saharia Ashish , Ghobrial R. Mark
Published: November 2022

Purpose of review

Liver transplantation for intrahepatic cholangiocarcinoma (iCCA) has been mired in controversy. High rates of recurrence posttransplant combined with donor organ scarcity resulted in most transplant centers treating iCCA as a contraindication for liver transplantation.

Recent findings

Recent studies have shown that carefully selected patients with unresectable iCCA can have good outcomes after liver transplantation. Better outcomes have been seen in patients with smaller tumors and favorable tumor biology.

Because many patients are diagnosed with iCCA at later stages, tumor biology and genetics are useful tools to identify patients who will have excellent overall and recurrence-free survival after liver transplantation. Further larger multicenter prospective studies are needed to identify patients who would benefit from liver transplantation with good outcomes. Additional advances will come through early diagnosis and utilizing a combination of chemotherapy and locoregional modalities as a bridge to transplant. There is also a need to recognize and develop additional neo- and adjuvant therapies for patients whose tumor biology currently precludes their inclusion on the liver transplantation waitlist.
Marginal parental donors for pediatric living donor liver transplantation
Authors: Kasahara Mureo , Sakamoto Seisuke , Fukuda Akinari , Uchida Hajime , Yi Nam-Joon , Schlegel Andrea , Muiesan Paolo , Qiang Xia , Gao Wei , Zhu Zhi-Jun , Rodriguez-Davalos Manuel , Rela Mohamed
Published: November 2022

Purpose of review

Living donor liver transplantation (LT) has been increasingly recognized as an effective treatment modality with excellent patient survival. Indications for LT have evolved not only for cholestatic liver disease, but also metabolic liver diseases. Living donor selection, particularly for pediatric inherited disease, is essential to prevent morbidity, both in the donor and recipient.

Recent findings

Based on 30 years of experience in pediatric living donor LT in Japan, we could identify marginal parental living donors who have potential risks following LT, including heterozygous mothers with ornithine transcarbamylase deficiency, heterozygous protein C deficiency, heterozygous hypercholesterolemia, heterozygous protoporphyria, asymptomatic parental donors with paucity of intrahepatic bile duct, and human leukocyte antigen-homozygous parental donors.

Although these situations seem rare due to infrequency of the condition, careful living donor evaluation is required to optimize the outcomes for pediatric recipients. In the setting of an appropriate selection of a living donor, we should avoid any additional hazards, given that the procedure itself has risks for a healthy individual.
Deceased donors with multidrug-resistant organisms: implications and future directions
Authors: Pouch Stephanie M. , Ison Michael G.
Published: November 2022

Purpose of review

Organ utilization from donors infected or colonized with multidrug-resistant organisms (MDROs) remains inconsistent, and hesitancy to accept organs from these donors may relate to poor outcomes among solid organ transplant recipients with MDRO donor-derived infections (DDIs). An improved understanding of the risk factors for donor MDRO colonization or infection and the risk of MDRO DDI is needed to safely expand the donor pool while minimizing unnecessary organ discard.

Recent findings

Recent studies have begun to delineate risk factors for MDRO acquisition among deceased donors and the epidemiology of MDRO DDIs, but additional efforts are warranted to inform optimal approaches to donor evaluation, risk stratification, management, interfacility and interagency data sharing, and approaches to recipient management.

This review summaries recent data regarding risk factors for MDRO colonization and infection in deceased donors, epidemiology of MDRO DDIs, and current approaches to donors harboring MDROs and provides a framework for future research and collaboration.
Human cytomegalovirus: a survey of end-organ diseases and diagnostic challenges in solid organ transplant recipients
Authors: Contreras Gustavo , Ho Dora
Published: November 2022

Purpose of review

Human cytomegalovirus (CMV) infection is one of the most important infectious complications in solid organ transplant (SOT) recipients, leading to significant morbidity and mortality. Therefore, early detection and prompt treatment are imperative to improve transplant outcomes. This article highlights the clinical characteristics of the most common CMV end-organ diseases in SOT recipients and their diagnostic modalities and challenges.

Recent findings

CMV can cause a variety of end-organ diseases in SOT recipients. Although CMV nucleic acid amplification by polymerase chain reaction (PCR) is frequently employed to detect CMV reactivation or infection, its predictive value for various CMV end-organ diseases remains uncertain. Given the limitation of PCR or other noninvasive tests, confirmation of CMV end-organ disease may require tissue biopsy, which may not be feasible or available, or may cause untoward complications.

The utility of PCR to diagnose CMV end-organ disease is limited. As CMV can infect any organ system(s), clinicians caring for SOT recipients need to maintain vigilance for any signs and symptoms of end-organ disease to allow early recognition and prompt treatment. Invasive procedures might be needed to confirm the diagnosis and minimize the empirical use of antiviral therapy that may have substantial drug toxicities.
Infective endocarditis in solid organ transplant: a review
Authors: Suarez Jose F. , Subramanian Aruna K.
Published: November 2022

Purpose of review

Infective endocarditis remains an uncommon disease with significant morbidity and mortality. In the last two decades, progress has been made describing the unique aspects of infective endocarditis in solid organ transplant (SOT) recipients.

Recent findings

Incidence of infective endocarditis in SOT is higher when compared with the general population. End-stage organ dysfunction, diabetes mellitus, older age, and prior intravenous lines have been identified as risk factors predisposing to infective endocarditis in SOT. Staphylococci and enterococci represent the most frequently isolated pathogens, whereas fungi are rarely isolated. Median time from transplantation to diagnosis ranges from 33 to 66 months. Nosocomial acquisition and mural endocarditis are more common in SOT recipients with infective endocarditis. Procurement of organs from patients with infective endocarditis might be well tolerated so long as close monitoring and targeted antibiotics are given. Selected patients might benefit from heart transplantation as definitive or salvage therapy for infective endocarditis. Outcomes of infective endocarditis in SOT recipients compared with the general population might be similar; however, patient survival and graft function are reduced when recipients suffer from infective endocarditis.

Infective endocarditis although rare can affect donors and recipients involved in the SOT process. Recognition of the unique characteristics in the presentation, prevention, medical, and surgical therapy of this disease is essential in order to minimize adverse outcomes.
Approaches to pretransplant vaccination
Authors: Kates Olivia S.
Published: November 2022

Purpose of review

The aim of this study was to summarize new data and perspectives in pretransplant vaccination, with a particular focus on COVID-19 vaccination and vaccination requirements.

Recent findings

Pretransplant vaccination produces superior markers of immunity and is expected to have greater clinical benefit, compared with posttransplant vaccination. As such, efforts are underway to identify and characterize barriers to pretransplant vaccination, with a particular focus on COVID-19 vaccine hesitancy. Unfortunately, vaccine hesitancy is common in transplant patients, often motivated by individual side effect and safety concerns. COVID-19 vaccination requirements have been implemented in some centres, informed by ethical principles, including beneficence, utility and justice.

Barriers to pretransplant vaccination can be understood in three categories: hard stops, including issues of vaccine availability, eligibility, safety and feasibility; soft stops, including issues of convenience, prioritization and care coordination; and volitional stops related to vaccine hesitancy and refusal. All of these barriers present opportunities for improvement based on recent data.
Novel agents in the treatment of invasive fungal infections in solid organ transplant recipients
Authors: Cabrera Nicolo L. , George Ige A. , Rauseo Adriana M. , Mazi Patrick , Spec Andrej
Published: November 2022

Purpose of review

Recipients of solid organ transplants (SOTs) suffer a significant burden of invasive fungal infections (IFIs). The emergence of drug-resistant fungi and toxicities of currently used antifungal agents as well as drug–drug interactions with immunosuppressants make their treatment challenging. This review discusses selected novel antifungal agents in the development pipeline that can currently be used through clinical trials or may be commercially available in the near future.

Recent findings

These agents in development have novel pharmacokinetics and pharmacodynamics, expanded spectra of activity and excellent safety profiles.

The properties of novel antifungal agents have the potential to expand the therapeutic options for IFIs in recipients of SOTs.
Preoperative patient optimization for endourological procedures: the current best clinical practice
Authors: Halawani Abdulghafour , Koo Kyo Chul , Wong Victor K.F. , Chew Ben H.
Published: November 2022

Purpose of review

Despite technological advancements in endourological surgery, there is room for improvement in preoperative patient optimization strategies. This review updates recent best clinical practices that can be implemented for optimal surgical outcomes.

Recent findings

Outcome and complication predictions using novel scoring systems and techniques have shown to assist clinical decision-making and patient counseling. Innovative preoperative simulation and localization methods for percutaneous nephrolithotomy have been evaluated to minimize puncture-associated adverse events. Novel antibiotic prophylaxis strategies and further recognition of risk factors that attribute to postoperative infections have shown the potential to minimize perioperative morbidity. Accumulating data on the roles of preoperative stenting and selective oral alpha-blockers adds evidence to the current paradigm of preventive measures for ureteral injury.

Ample tools and technologies exist that can be utilized preoperatively to improve surgical outcomes. The combination of these innovations, along with validation in larger-scale studies, presents the cornerstone of future urolithiasis management.
Selective Skeletal Surveys for Infants With Skull Fractures
Authors: Dominguez Michelle M. , Moore Jessica L. , Cook Megan , Rogers Michelle L. , McCarten Kathleen , Slingsby Brett
Published: November 2022

Objectives

This study aimed to describe which infants with a skull fracture (1) receive a child abuse pediatrician (CAP) consultation, (2) receive a skeletal survey, and (3) re-present to medical care before age 3 years with concerns for physical abuse.

Methods

We conducted a retrospective chart review of infants younger than 12 months who presented to the emergency department between January 1, 2005, and December 30, 2015, with a skull fracture. Medical records were reviewed for the skull fracture presentation and for all future medical evaluations at the same institution with concerns for physical abuse until 3 years of age.

Results

Of 366 infants with a skull fracture, a CAP was contacted for 272 (74%) and 76 (20.8%) infants who received a skeletal survey. Factors associated with skeletal survey acquisition included younger age (<6 months), no history to explain the skull fracture, other injuries on examination, and social risk factors. Six children (1.6%) re-presented to medical care with concerns of physical abuse before age 3 years. Five of these infants did not have a skeletal survey at the time of their skull fracture, and 1 was likely a case of missed physical abuse at the time of the skull fracture.

Discussion

Most skull fractures in infancy occur accidentally, and a skeletal survey may not be necessary for every infant. Obtaining a thorough history including social risk factors, performing a complete physical examination, and consulting with a CAP is an effective first step in the evaluation of physical abuse in infants with skull fractures.
Medications, Genes, Environmental Stress, and Pursuit of Recovery
Authors: Plakun Eric M.
Published: November 2022

This column summarizes the findings of 2 recent studies of interest to psychotherapists. One study reports that the use of antidepressant medication is not associated with long-term improvement in health-related quality of life, while the other finds that psychotic experiences in adolescents are more closely associated with environmental experiences than with genetic risk. The column discusses the implications of these studies for psychotherapists and for the field at large.
HIV infection drives pro-inflammatory immunothrombotic pathway activation and organ dysfunction among adults with sepsis in Uganda
Authors: Cummings Matthew J. , Bakamutumaho Barnabas , Price Adam , Owor Nicholas , Kayiwa John , Namulondo Joyce , Byaruhanga Timothy , Jain Komal , Postler Thomas S. , Muwanga Moses , Nsereko Christopher , Nayiga Irene , Kyebambe Stephen , Che Xiaoyu , Sameroff Stephen , Tokarz Rafal , Shah Shivang S. , Larsen Michelle H. , Lipkin W. Ian , Lutwama Julius J. , O’Donnell Max R.
Published: November 2022

Background:

The global burden of sepsis is concentrated in high HIV-burden settings in sub-Saharan Africa (SSA). Despite this, little is known about the immunopathology of sepsis in persons with HIV (PWH) in the region. We sought to determine the influence of HIV on host immune responses and organ dysfunction among adults hospitalized with suspected sepsis in Uganda.

Design:

Prospective cohort study.

Methods:

We compared organ dysfunction and 30-day outcome profiles of PWH and those without HIV. We quantified 14 soluble immune mediators, reflective of key domains of sepsis immunopathology, and performed whole-blood RNA-sequencing on samples from a subset of patients. We used propensity score methods to match PWH and those without HIV by demographics, illness duration, and clinical severity, and compared immune mediator concentrations and gene expression profiles across propensity score-matched groups.

Results:

Among 299 patients, 157 (52.5%) were PWH (clinical stage 3 or 4 in 80.3%, 67.7% with known HIV on antiretroviral therapy). PWH presented with more severe physiologic derangement and shock, and had higher 30-day mortality (34.5% vs. 10.2%; P < 0.001). Across propensity score-matched groups, PWH exhibited greater pro-inflammatory immune activation, including upregulation of interleukin (IL)-6, IL-8, IL-15, IL-17 and HMGB1 signaling, with concomitant T-cell exhaustion, prothrombotic pathway activation, and angiopoeitin-2-related endothelial dysfunction.

Conclusions:

Sepsis-related organ dysfunction and mortality in Uganda disproportionately affect PWH, who demonstrate exaggerated activation of multiple immunothrombotic and metabolic pathways implicated in sepsis pathogenesis. Further investigations are needed to refine understanding of sepsis immunopathology in PWH, particularly mechanisms amenable to therapeutic manipulation.
Evaluation of tangential flow filtration coupled to long-read sequencing for ostreid herpesvirus type 1 genome assembly
Authors: Dotto-Maurel Aurélie , Pelletier Camille , Morga Benjamin , Jacquot Maude , Faury Nicole , Dégremont Lionel , Bereszczynki Maëlis , Delmotte Jean , Escoubas Jean-Michel , Chevignon Germain
Published: November 2022

Whole-genome sequencing is widely used to better understand the transmission dynamics, the evolution and the emergence of new variants of viral pathogens. This can bring crucial information to stakeholders for disease management. Unfortunately, aquatic virus genomes are usually difficult to characterize because most of these viruses cannot be easily propagated in vitro. Developing methodologies for routine genome sequencing of aquatic viruses is timely given the ongoing threat of disease emergence. This is particularly true for pathogenic viruses infecting species of commercial interest that are widely exchanged between production basins or countries. For example, the ostreid herpesvirus type 1 (OsHV-1) is a Herpesvirus widely associated with mass mortality events of juvenile Pacific oyster Crassostrea gigas. Genomes of Herpesviruses are large and complex with long direct and inverted terminal repeats. In addition, OsHV-1 is unculturable. It therefore accumulates several features that make its genome sequencing and assembly challenging. To overcome these difficulties, we developed a tangential flow filtration (TFF) method to enrich OsHV-1 infective particles from infected host tissues. This virus purification allowed us to extract high molecular weight and high-quality viral DNA that was subjected to Illumina short-read and Nanopore long-read sequencing. Dedicated bioinformatic pipelines were developed to assemble complete OsHV-1 genomes with reads from both sequencing technologies. Nanopore sequencing allowed characterization of new structural variations and major viral isomers while having 99,98 % of nucleotide identity with the Illumina assembled genome. Our study shows that TFF-based purification method, coupled with Nanopore sequencing, is a promising approach to enable in field sequencing of unculturable aquatic DNA virus.
Grading the pungency of red pepper powder using hyperspectral
imaging coupled with multivariate analysis
Authors: Choi Ji-Young , Cho Jeong-Seok , Park Kee Jai , Kim Sang Seop , Lim Jeong-Ho
Published: November 2022

In this study, the spectral image of red pepper powder, which had been prepared
in accordance with the standard particle size distribution ratio, was acquired
in the short-wave infrared region using a hyperspectral camera. Spectral
information was analyzed using multivariate statistical analyses including
principal component analysis (PCA) and least partial squares (PLS) analysis. PCA
revealed that powders were grouped according to their pungency level, regardless
of their particle size distribution (PC1=97%,
PC2=2%). The regression coefficient derived in PLS discriminant
analysis indicated that 1,201-1,226 nm, 1,387-1,411 nm, and 1,508-1,529 nm are
key wavelengths that are affected by the vibration of C-H, O-H, and N-H bonds
present in capsaicinoid molecules. Pungency grade was successfully determined,
and capsaicinoid content was predicted with high accuracy using PLS analysis of
raw data at key wavelength (Rc2=0.9389,
Rp2= 0.9261). It was possible to reduce the
time required for data calculation and analysis by reducing the amount of
spectral data utilized to predict spiciness from 256 to 21 bands. Finally, the
distribution of capsaicinoids was mapped visually according to particle size. In
conclusion, hyperspectral imaging is a suitable technology for real time,
non-destructive monitoring of red pepper powder quality relative to the standard
method used during the manufacturing process.
Measurement of 24-hour Continuous Human CH4Release in a Whole Room Indirect Calorimeter
Authors: Carnero E.A. , Bock C.P. , Liu Y. , Corbin K.D. , Wohlers-Kariesch E. , Ruud K. , Moon J. , Andrew M. , Krajmalnik-Brown R. , Muraviev A. , Vodopyanov K.L. , Smith S.R.
Published: November 2022

We describe the technology and validation of a new whole room indirect calorimeter (WRIC) methodology to quantify methane (CH4) released from the human body over 24h concurrently with the assessment of energy expenditure and substrate utilization. The new system extends the assessment of energy metabolism by adding CH4, a downstream product of microbiome fermentation that could contribute to energy balance.

Methods

Our new system consists of an established whole room indirect calorimeter WRIC combined with the addition of off-axis integrated-cavity output spectroscopy (OA-ICOS) to measure CH4concentrations ([CH4]). The volume of CH4released (VCH4) was calculated after measuring air flow rates. Development and validation included environmental experiments to measure the stability of the atmospheric [CH4], infusing CH4into the WRIC and cross-validation studies comparing [CH4] quantified by OA-ICOS and mid-infrared dual-comb spectroscopy (MIR DCS). Reliability of the whole system is reported between years, weeks, days, and validated CH4infusions. The cross-validation and reliability of VCH4released from the human body was determined in 19 participants on consecutive days. In addition, we describe a postprocessing analytical method to differentiate CH4released from breath versus intestine by matching times of stool production and contemporaneous VCH4release.

Results

Our infusion data indicated that the system measured 24h [CH4] and VCH4with high sensitivity, reliability and validity. Cross-validation studies showed good agreement between OA-ICOS and MIR DCS technologies (r= 0.979, P<0.0001). Initial human data revealed 24h VCH4was highly variable between subjects and within / between days; this highlights the importance of a 24-h continuous assessment to have a complete picture of VCH4 release. Finally, our method to quantify VCH4released by breath or colon suggested that over 50% of the CH4was eliminated through the breath.

Conclusions

The method allows, for the first time, measurement of 24h VCH4(in kcal) and therefore the measurement of the proportion of human energy intake fermented to CH4by the gut microbiome and released via breath or directly from the intestine. Our method is accurate, valid, and will provide meaningful data to understand not only interindividual variation, but also allows us to track the effects of dietary, probiotic, bacterial and fecal microbiota transplantation on VCH4.
Evaluating the use of dose-sparing vaccination strategies for Monkeypox
Authors: Dimitrov Dobromir , Adamson Blythe , Matrajt Laura
Published: November 2022

The spring-summer 2022 monkeypox outbreak had over 50,000 cases globally, most of them in gay, bisexual, and other men who have sex with men (MSM). In response to vaccine shortages, several countries implemented dose-sparing vaccination strategies, stretching a full-dose vaccine vial in up to 5 fractional-dose vaccines. Recent studies have found mixed results regarding the effectiveness of the monkeypox vaccine, raising the question of the utility of dose-sparing strategies. We used an age- and risk-stratified mathematical model of an urban MSM population in the United States with approximately 12% high-risk MSM to evaluate potential benefits from implementing dose-sparing vaccination strategies in which a full dose is divided in 3.5 fractional-doses. We found that results strongly depend on the fractional-dose vaccine effectiveness (VE) and vaccine supply. With very limited vaccine available, enough to protect with a full-dose approximately one-third of the high-risk population, dose-sparing strategies are more beneficial provided that fractional-dose preserved at least 40% of full dose effectiveness (34% absolute VE), projecting 13% (34% VE) to 70% (68% absolute VE) fewer infections than full-dose strategies. In contrast, if vaccine supply is enough to cover the majority of the high-risk population, dose-sparing strategies can be outperformed by full-dose strategies. Scenarios in which fractional-dosing was 34% efficacious result in almost three times more infections than full-dosing. Our analysis suggests that when monkeypox vaccine supply is limited and fractional-dose vaccination retains moderate effectiveness, there are meaningful health benefits from providing a smaller dose to a larger number of people in the high-risk population.
High-dimensional immune profiling of dimethyl fumarate and ocrelizumab in multiple sclerosis
Authors: Zhang Yinan , Lee Brian , Xie Hui , Rockoff Jonathan , Satyanarayan Sammita , Brandstadter Rachel , Kim-Schulze Seunghee , Ntranos Achillefs , Lublin Fred
Published: November 2022

Background

Dimethyl fumarate (DMF) and ocrelizumab are two effective immunomodulators for multiple sclerosis (MS) with distinct mechanisms of action. Identifying overlapping therapeutic effects between both agents may elucidate common pathways in preventing disease activity.

Objectives

In this study we analyzed cytokine and immune-profiling data to evaluate the similarities and differences between the two disease-modifying therapies for MS.Methods: Plasma and PBMCs from MS patients were collected at baseline, 3 months and 6 months after treatment with DMF (n=16) and ocrelizumab (n=13). Immunophenotyping was performed with mass cytometry (CyTOF) and analyzed with gating based on cell surface markers. Cytokine analysis from plasma was performed with Olink assays and analyzed with linear mixed effects models.

Results

DMF reduced both effector T and memory B cell populations while increasing CD56brightnatural killer (NK) cells. Ocrelizumab exerted its main immunomodulatory effect by reducing the frequency of all B cells and increasing frequency of NK cells. At 6 months, naive B-cells began to reconstitute; however, memory B cells remain depleted. DMF treatment was associated with a significant reduction of plasma cytokines involved in inflammatory pathways, such as IL-6, IL-12, and Dectin-1 signaling. In addition, DMF lowered plasma cytokines that are dysregulated in psoriasis and involved in allograft rejection pathways. Ocrelizumab treatment led to the upregulation of neurotropic proteins in the plasma of MS patients, including proteins involved in NAD+ biosynthesis and tryptophan catabolism.

Conclusion

Our high-dimensional immunophenotyping results suggest that to exert their effects on MS patients, DMF and ocrelizumab both increase NK cells in addition to affecting different immune cell populations and cytokine pathways. Detecting similarities between the mechanisms of the two drugs may contribute to identifying more specific therapeutic targets.
Clinical accuracy of SARS-CoV-2 rapid antigen testing in screening children and adolescents in comparison to RT-qPCR, November 2020 to September 2022
Authors: Krone Manuel , Wagenhäuser Isabell , Knies Kerstin , Hofmann Daniela , Engels Geraldine , Taurines Regina , McDonogh Miriam , Flemming Sven , Meyer Thomas , Böhm Hartmut , Scherzad Agmal , Eisenmann Michael , Rauschenberger Vera , Gabel Alexander , Petri Nils , Reusch Julia , Forster Johannes , Weißbrich Benedikt , Dölken Lars , Kurzai Oliver , Vogel Ulrich , Härtel Christoph , Liese Johannes , Andres Oliver
Published: November 2022

Background

Rapid antigen detection tests (RDT) are an easily accessible, feasible, inexpensive, and point-of-care method in SARS-CoV-2 diagnostics – established in adults as well as in children and adolescents. Despite this, large-scale data of clinical performance in the paediatric population especially regarding the influence of SARS-CoV-2 virus variants of concern (VOC) and COVID-19 vaccination on test accuracy is rare.

Methods

This single-centre prospective diagnostic study evaluates three RDT (NADAL®, Panbio™, MEDsan®) in comparison to quantitative reverse transcription polymerase chain reaction (RT-qPCR). 9,760 oropharyngeal screening samples regarding SARS-CoV-2 VOC and COVID-19 vaccination in paediatric hospitalised patients aged younger than 18 years were enrolled.

Findings

RDT sensitivity was 44·7% (157/351, 95% CI 39·6%–50·0%) compared to the reference standard RT-qPCR, specificity 99·8% (9,392/9,409, 95% CI 99·7%–99·9%). Most SARS-CoV-2 infections considered were caused by Omicron VOC. Diagnostic accuracy of RDT depended on specimen containing viral load with a decreasing RDT sensitivity by descending viral load, corresponding with a significantly impaired sensitivity in asymptomatic children. A sensitivity of 71·0% was obtained for a viral load higher than 106SARS-CoV-2 RNA copies per ml suggested as infectivity threshold. No significant differences in RDT sensitivity could be observed regarding gender, symptoms, COVID-19 vaccination status, and VOC.

Interpretation

In a paediatric population, RDT have proven to reliably detect potentially highly infectious patients with a viral load of at least 106SARS-CoV-2 RNA copies per ml. Due to the low sensitivity in asymptomatic individuals, the usefulness of RDT seems limited in large-scale SARS-CoV-2 screening programs.

Funding

Federal Ministry for Education and Science (BMBF), Free State of Bavaria
Music sound quality assessment in bimodal cochlear implant users – toward improved hearing aid fitting
Authors: Abdellatif Khaled H. A. , Müller Verena , Walger Martin , Meister Hartmut
Published: November 2022

The use of cochlear implants (CI) is the common treatment to counteract severe-profound hearing loss. CI often allow reasonable speech understanding but are generally limited in terms of spectro-temporal resolution. Many CI recipients use a hearing aid (HA) on the non-implanted ear (so called bimodal patients) that complements the electrical stimulation of the CI by providing acoustical fine structure information. Amongst others, this might be especially beneficial for music appraisal. However, it is not clear how the HA should be fitted in conjunction with the CI in order to provide the best sound quality.

The purpose of this study was to vary different fitting parameters of the HA systematically and to determine the resulting music sound quality. To this end, a master hearing aid was used in order to have controlled access to the different parameters. Three different music excerpts (pop with and without vocals, classic) were presented to 13 bimodally fitted CI users and the sound quality was assessed using the “multiple-stimulus with hidden reference and anchor” (MUSHRA) test. Since the goal was to gain information on possible improvement of fitting, a complete retest was performed and individual reliability of the assessments was determined by the eGauge method.

It could be shown that most of the listeners were able to provide reliable sound quality judgements. In terms of HA fitting it turned out that changing compression and varying low frequency gain had a significant effect compared to a standard prescriptive fitting based on DSL v5.0. However, especially the effect of changing low frequency gain depended on the music excerpts presented, since pop music with vocals revealed the largest effect.

The study gives evidence that hearing aid fitting can be optimized relative to a standard prescriptive rule in order to improve music sound quality in bimodal CI users. Moreover, the method might be helpful in a clinical setting to determine the best fitting based on individual results.
Estimating the seroincidence of scrub typhus using antibody dynamics following infection
Authors: Aiemjoy Kristen , Katuwal Nishan , Vaidya Krista , Shrestha Sony , Thapa Melina , Teunis Peter , Bogoch Isaac I. , Trowbridge Paul , Kantipong Pacharee , Blacksell Stuart D. , Wangrangsimakul Tri , Varghese George M , Maude Richard , Tamrakar Dipesh , Andrews Jason R.
Published: November 2022

Introduction

Scrub typhus is an acute febrile illness caused by the bacteriumOrientia tsutsugamushi. Characterizing the population-level burden of scrub typhus is challenging due to the lack of accessible and accurate diagnostics. In this study, we present a novel approach that utilizes information on antibody dynamics after infection to generate population-level scrub typhus seroincidence estimates from cross-sectional serosurveys.

Methods

We use data from three cohorts of scrub typhus patients enrolled in Chiang Rai, Thailand, and Vellore, India, and representative population data from two serosurveys in and around the Kathmandu valley, Nepal, and Vellore, India. The samples were tested for IgM and IgG responses toOrientia tsutsugamushi-derived recombinant 56-kDa antigen using commercial ELISA kits. We used Bayesian hierarchical models to fit two-phase models to the antibody responses from scrub typhus cases and used the joint distributions of the peak antibody titers and decay rates to estimate population-level incidence rates in the cross-sectional serosurveys. We compared this new method to a traditional cut-off-based approach for estimating seroincidence.

Results

Median IgG antibodies persisted above OD 1.7 for 22 months, while IgM displayed longer persistence than expected, with 50% of participants having an OD >1 for 5 months. We estimated an overall seroincidence of 18 per 1000 person-years (95% CI: 16-21) in India and 4 per 1000 person-years (95% CI: 3-6) in Nepal. Among 18 to 29-year-olds, the seroincidence was 8 per 1000 person-years (95% CI 4 -16) in India and 9 per 1000 person-years (95% CI: 6-14) in Nepal. In both India and Nepal, seroincidence was higher in urban and periurban settings compared to rural areas. Compared to our method, seroincidence estimates derived from age-dependent IgG-seroprevalence without accounting for antibody decay underestimated the disease burden by 50%. By incorporating antibody dynamics, the approach described here provides more accurate age-specific infection risk estimates, emphasizing the importance of considering both IgG and IgM decay patterns in scrub typhus seroepidemiology.

Conclusion

The sero-surveillance approach developed in this study efficiently generates population-level scrub typhus seroincidence estimates from cross-sectional serosurveys. This methodology offers a valuable new tool for informing targeted prevention and control strategies, ultimately contributing to a more effective response to scrub typhus in endemic regions worldwide.