bluuebunny/crossref_metadata_2025 huggingface dataset:
Re-examining Hepatitis B Postexposure Prophylaxis Following Pediatric Community-acquired Needle-stick Injury in an Era of a National Immunization Registry
Authors: Ewe Krist Y.H. , Blyth Christopher C. , McLeod Charlie , Borland Meredith L. , Bowen Asha C. , Yeoh Daniel K. , Campbell Anita J.
Published: December 2021

Background:

Long-term hepatitis B immunity has been demonstrated following the completion of the primary vaccination series in childhood. Some guidelines recommend a hepatitis B surface antibody (anti-HBs) directed approach following community-acquired needle-stick injury (CANSI) to inform hepatitis B postexposure prophylaxis (PEP) management. We assessed the utility of anti-HBs testing post-CANSI, as well as the costing of, and adherence to PEP at a pediatric hospital.

Methods:

Children presenting to an Australian tertiary pediatric hospital post-CANSI (2014–2019) were identified retrospectively using medical and laboratory records. Immunization status was obtained from the Australian Immunisation Registry.

Results:

Fifty-six children with CANSI were identified. Of those with immunization records, all had completed hepatitis B vaccinations (n = 52). At presentation, 44% (n = 23) had anti-HBs <10 IU/L, which was more likely in older (≥6 years, 68%) versus younger children (OR 4.59, P < 0.02). HBIG and hepatitis B vaccine adherence was 65% (15/23) and 78% (18/23), respectively. All children (n = 14) with anti-HBs ≥4 weeks postvaccination ±HBIG, demonstrated an anamnestic response. No hepatitis B infections were detected. Using completed immunizations versus anti-HBs levels as a marker of immunity to direct PEP resulted in a projected cost savings of AUD$ 4234.

Conclusion:

Anti-HBs levels <10 IU/L, despite previous vaccinations, were frequent in children post-CANSI, with many demonstrating an anamnestic response. Adherence to postexposure HBIG and hepatitis B vaccine was suboptimal using an anti-HBs directed approach. These data support re-evaluating PEP in an era of the national immunization registry; completion of hepatitis B vaccinations as a marker of immunity provides a practical approach, ensuring optimized care for pediatric CANSI.
Pediatric Parapneumonic Effusion/Pleural Empyema in Japan
Authors: Hoshino Tadashi , Nishima Daisuke , Enseki Mayumi , Umehara Naoki , Fukasawa Chie , Ishiwada Naruhiko
Published: December 2021

Background:

Pediatric parapneumonic effusion/ pleural empyema (PPE/PE) is a severe infectious condition, and its management should be guided by local epidemiology and the patient’s medical history. This survey aimed to determine the clinical and bacteriologic features of PPE/PE in Japan.

Methods:

A nationwide retrospective questionnaire survey was conducted, targeting 159 pediatric specialist training medical facilities for inpatients ≤18 years of age who were admitted for PPE/PE between January 2007 and December 2016.

Results:

Valid responses were obtained from 122 facilities, and 96 patients were identified from 38 facilities. The median age (interquartile range) was 2.7 (0.8–7.8) years. Overall, 60 (63 %) patients were men and 49 (51%) had comorbidities. The causative bacteria were identified in 59% of patients by culture except in one case identified using PCR. Streptococcus pyogenes (16%), Staphylococcus aureus (14%) and Streptococcus pneumoniae (13%) were the major pathogens. Carbapenems were administered to 34% of patients without comorbidities. Chest tube drainage was performed in 71%, intrapleural fibrinolytic therapy in 9.4%, surgery in 25% and mechanical ventilation in 29% of the patients. Five patients (5.2%) had complications and one (1.1%) had sequelae, but all patients (100%) survived.

Conclusions:

This is first report of a nationwide survey pertaining to pediatric PPE/PE in Japan. We found that the etiology showed a different trend from that reported in other countries. It is worrisome that molecular methods were rarely used for pathogenic diagnosis and carbapenems were overused. Thus, it is imperative to establish clinical guidelines for PPE/PE in Japan.
Differential Impact of Nonpharmaceutical Interventions on the Epidemiology of Invasive Bacterial Infections in Children During the Coronavirus Disease 2019 Pandemic
Authors: Kim Ye Kyung , Choi Youn Young , Lee Hyunju , Song Eun Song , Ahn Jong Gyun , Park Su Eun , Lee Taekjin , Cho Hye-Kyung , Lee Jina , Kim Yae-Jean , Jo Dae Sun , Kang Hyun Mi , Lee Joon Kee , Kim Chun Soo , Kim Dong Hyun , Kim Hwang Min , Choi Jae Hong , Eun Byung Wook , Kim Nam Hee , Cho Eun Young , Kim Yun-Kyung , Oh Chi Eun , Kim Kyung-Hyo , Choi Eun Hwa
Published: December 2021

Background:

Invasive bacterial infection (IBI) remains a major burden of mortality and morbidity in children. As coronavirus disease 2019 (COVID-19) emerged, stringent nonpharmaceutical interventions (NPIs) were applied worldwide. This study aimed to evaluate the impact of NPIs on pediatric IBI in Korea.

Methods:

From January 2018 to December 2020, surveillance for pediatric IBIs caused by 9 pathogens (S. pneumoniae, H. influenzae, N. meningitidis, S. agalactiae, S. pyogenes, S. aureus, Salmonella species, L. monocytogenes and E. coli) was performed at 22 hospitals throughout Korea. Annual incidence rates were compared before and after the COVID-19 pandemic.

Results:

A total of 651 cases were identified and the annual incidence was 194.0 cases per 100,000 in-patients in 2018, 170.0 in 2019 and 172.4 in 2020. Most common pathogen by age group was S. agalactiae in infants < 3 months (n = 129, 46.7%), S. aureus in 3 to < 24 months (n = 35, 37.2%), Salmonella spp. in 24 to < 60 months (n = 24, 34.8%) and S. aureus in children ≥ 5 years (n = 128, 60.7%). Compared with 2018 to 2019, the incidence rate in 2020 decreased by 57% for invasive pneumococcal disease (26.6 vs. 11.5 per 100,000 in-patients, P = 0.014) and 59% for Salmonella spp. infection (22.8 vs. 9.4 per 100,000 in-patients, P = 0.018). In contrast, no significant changes were observed in invasive infections due to S. aureus, S. agalactiae and E. coli.

Conclusions:

The NPIs implemented during the COVID-19 pandemic reduced invasive diseases caused by S. pneumoniae and Salmonella spp. but not S. aureus, S. agalactiae and E. coli in children.
Amoxicillin Adverse Cutaneous Reaction Versus Post Streptococcal Vasculitis
Authors: Liccioli Giulia , Parronchi Paola , Marrani Edoardo , Maniscalco Valerio , Giovannini Mattia , Barni Simona , Sarti Lucrezia , Capone Manuela , Simonini Gabriele , Mori Francesca
Published: December 2021

In children, skin rashes are a frequent manifestation of infectious diseases, or they could also be the result of a drug hypersensitivity reaction, especially after antibiotic intake. We report the case of a 5-year-old girl investigated for a suspected post streptococcal vasculitis where differential diagnosis was improved by an allergy work-up and confirmed by lymphocyte transformation test.
Chronic pain in the 11th Revision of the International Classification of Diseases: users' questions answered
Authors: Korwisi Beatrice , Barke Antonia , Rief Winfried , Treede Rolf-Detlef , Kleinstäuber Maria
Published: December 2021

For the first time, the upcoming International Classification of Diseases and Related Health Problems, Eleventh Revision (ICD-11) will include a comprehensive classification of chronic pain, which is based on the biopsychosocial definition of chronic pain. This presents a great opportunity for pain research and clinical practice. The new classification consists of 7 main diagnostic categories of chronic pain, which are further divided into increasingly specific levels of diagnoses. Each diagnosis is characterized by clearly defined operationalized criteria. Future users will need to familiarize themselves with the new system and its application. The aim of the present publication is to provide users of the ICD-11 chronic pain classification with answers to frequently asked questions regarding the ICD-11 as a whole, the ICD-11 chronic pain classification, and its application to common pain syndromes. The questions compiled in this study reached the International Association for the Study of Pain Task Force through different routes (eg, at conferences, by letter, or during field testing). Furthermore, the authors collected questions posted to the ICD-11 browser and contacted early users of the classification to enquire about their most frequent difficulties when applying the new diagnoses. The authors of the present publication prepared answers to these frequently asked questions. This publication intends to act as a guide for the future users of the new ICD-11 chronic pain classification, hence facilitating its implementation.
Prolonged sitting time links to subclinical atherosclerosis
Authors: Lim Su Shen , Huang Chin-Chou , Hsu Pai-Feng , Lin Chung-Chi , Wang Yuan-Jen , Ding Yaw-Zon , Liou Teh-Ling , Wang Ying-Wen , Huang Shao-Sung , Lu Tse-Min , Chen Jaw-Wen , Chan Wan-Leong , Lin Shing-Jong , Leu Hsin-Bang
Published: December 2021

Background:

This study investigates the association between daily sitting time and subclinical atherosclerosis by using coronary computed tomography angiography (CCTA).

Methods:

The study enrolled 203 subjects (age 57.6 ± 8.8 years) who underwent CCTA at annual medical checkups. Sitting time was categorized as < 5 hours/day (short), 5 to 9 hours/day (moderate) and ≥10 hours/d (long). We analyzed the coronary calcium score, plaque characteristics, and severity of coronary artery stenosis, including the segment involvement score (SIS) and segment stenosis score (SSS).

Results:

Subjects with longer sitting times tended to be male gender and have lower levels of high-density lipoprotein cholesterol (p for trend < 0.05). In addition, those with longer sitting time had higher SIS (1.2 ± 1.5 vs. 1.6 ± 2.1 vs. 2.3 ± 2.0 for short, moderate, and long sitting time, respectively) (p for trend = 0.015) and SSS (1.4 ± 2.0 vs. 1.9 ± 2.7 vs. 2.7 ± 2.6) (p for trend = 0.015), suggesting longer sitting time-correlated with the severity of coronary atherosclerosis. When considering the coronary plaque patterns, subjects with shorter sitting time (<5 hours/d) tended to have more calcified plaque and subjects with longer sitting time (≥10 hours/d) had more mixed plaque (p for trend = 0.018). After adjusting for age, gender, comorbidities, body mass index, and lipid profiles, increased sitting time was independently associated with the presence of mixed plaque, suggesting longer sitting time may be associated with higher risk of the formation of vulnerable plaque.

Conclusion:

Longer sitting time was linked to the severity of subclinical atherosclerosis and the presence of high-risk vulnerable plaque in the general population.
Using big data of genetics, health claims, and brain imaging to challenge the categorical classification in mental illness
Authors: Su Tung-Ping , Chen Mu-Hong , Tu Pei-Chi
Published: December 2021

Psychiatric disorders in first-degree relatives (FDRs) often differ from the index patient’s diagnosis, suggesting that there is genetic contribution to psychiatric disorders in which related cases do not all map to the same diagnosis as the index case. Our aim is to look for psychiatric comorbidities across major mental illnesses using three approaches, genetics, clinical diagnosis, and brain imaging to address common associations and pathology among mental illnesses. Genome-wide association studies from the Psychiatric Genomics Consortium showed single gene polymorphisms are common across 5 major psychiatric disorders, including schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD). Clinically, results of Taiwan’s nationwide population studies showed that other major psychiatric disorders were more likely to coaggregate in families with an index case of an individual with a psychiatric disorder, compared to control families. Finally, resting functional connectivity (FC) magnetic resonance imaging (MRI) and whole-brain connectomic analysis of SZ, BD I, BD II, MDD, and healthy controls revealed that the four groups of patients shared similar patterns of abnormal neural substrate in the brain that differed from controls. In conclusion, using big data from genetics, administrative health claims, and brain imaging, we identified concordance, indicating dimensional coherence of genetic heritability, clinical mutual associations, and common neurobiological substrates across major psychiatric disorders. These results will challenge the current diagnostic classification system and possibly move psychiatry beyond descriptive syndromes towards a nosology informed by disease cause.
Symptoms of Acute Myocardial Infarction as Described in Calls to Tele-Nurses and in Questionnaires
Authors: Ängerud Karin Hellström , Ericsson Maria , Brännström Margareta , Sederholm Lawesson Sofia , Strömberg Anna , Thylén Ingela
Published: December 2021

Background

Patient-reported symptoms of acute myocardial infarction (MI) may be affected by recall bias depending on when and where symptoms are assessed.

Aim

The aim of this study was to gain an understanding of patients' symptom description in more detail before and within 24 hours after a confirmed MI diagnosis.

Methods

A convergent parallel mixed-methods design was used to examine symptoms described in calls between the tele-nurse and the patient compared with symptoms selected by the patient from a questionnaire less than 24 hours after hospital admission. Quantitative and qualitative data were analyzed separately and then merged into a final interpretation.

Results

Thirty patients (median age, 67.5 years; 20 men) were included. Chest pain was the most commonly reported symptom in questionnaires (24/30). Likewise, in 19 of 30 calls, chest pain was the first complaint mentioned, usually described together with the symptom onset. Expressions used to describe symptom quality were pain, pressure, discomfort, ache, cramp, tension, and soreness. Associated symptoms commonly described were pain or numbness in the arms, cold sweat, dyspnea, weakness, and nausea. Bodily sensations, such as feeling unwell or weak, were also described. Fear and tiredness were described in calls significantly less often than reported in questionnaires (P = .01 and P = .02), whereas “other” symptoms were more often mentioned in calls compared with answers given in the questionnaire (P = .02). Some symptoms expressed in the calls were not listed in the questionnaire, which expands the understanding of acute MI symptoms. The results showed no major inconsistencies between datasets.

Conclusion

Patients' MI symptom descriptions in tele-calls and those reported in questionnaires after diagnosis are comparable and convergent.
Targeted Therapeutics for Transthyretin Amyloid Cardiomyopathy
Authors: Campbell Courtney M. , Baiyee Cyril Ayuk Mbeng Takem , Almaani Salem , Bumma Naresh , Sharma Nidhi , LoRusso Samantha , Redder Elyse , Bittengle Jordan , Pfund Katherine , Friemer Miriam , Tong Matthew , Kahwash Rami , Efebera Yvonne , Parikh Samir , Vallakati Ajay
Published: December 2021

Background:

Deposition of wild-type or mutant transthyretin (TTR) amyloid fibrils in the myocardium causes TTR amyloid cardiomyopathy (ATTR-CM). Targeted therapeutics for ATTR-CM include TTR stabilizers (tafamidis and diflunisal) and oligonucleotide drugs (revusiran, patisiran, and inotersen). TTR stabilizers prevent dissociation of transthyretin tetramers. Transthyretin monomers can misfold and form amyloid fibrils. TTR stabilizers thereby limit amyloid fibrils development and deposition. Oligonucleotide drugs inhibit hepatic synthesis of transthyretin, which decreases transthyretin protein levels and thus the amyloid fibril substrate.

Areas of Uncertainty:

To study the safety and efficacy of targeted therapeutics in patients with ATTR-CM, we performed a pooled analysis. A random-effects model with the Mantel–Haenszel method was used to pool the data.

Data Sources:

A literature search was performed using PubMed, Cochrane CENTRAL, and Embase databases using the search terms “cardiac amyloidosis” AND “tafamidis” OR “patisiran” OR “inotersen” OR “revusiran” OR “diflunisal.”

Therapeutic Advances:

We identified 6 studies that compared targeted therapeutics with placebo. One study was stopped prematurely because of increased mortality in the targeted therapeutics arm. Pooled analysis included 1238 patients, of which 738 patients received targeted therapeutics and 500 patients received placebo. When compared with placebo, targeted therapeutics significantly reduced all-cause mortality [OR 0.39, 95% confidence interval (CI): 0.16–0.97, P = 0.04]. Only 2 studies reported the effect on cardiovascular-related hospitalizations. There was a trend toward an improvement in global longitudinal strain (mean difference −0.69, 95% CI: −1.44 to 0.05, P = 0.07). When compared with placebo, there was no increase in serious adverse events with targeted therapeutics (OR 1.06, 95% CI: 0.78–1.44, P = 0.72).

Conclusion:

Evidence from the pooled analysis revealed targeted therapeutics improve survival and are well-tolerated. These findings suggest a potential role for targeted therapeutics in the treatment of patients with ATTR-CM.
Sodium–Glucose Cotransporter Inhibitors Reduce Mortality and Morbidity in Patients With Heart Failure: Evidence From a Meta-Analysis of Randomized Trials
Authors: Camilli Massimiliano , Lombardi Marco , Chiabrando Juan G. , Zito Andrea , Del Buono Marco G. , Vergallo Rocco , Aspromonte Nadia , Lombardo Antonella , Montone Rocco A. , Niccoli Giampaolo , Biondi-Zoccai Giuseppe , Crea Filippo , Minotti Giorgio
Published: December 2021

Background:

Recent trials demonstrated the clinical efficacy of sodium–glucose cotransporter-2 inhibitors (SGLT2i) in patients with heart failure (HF), regardless of the presence or absence of type 2 diabetes. These data may allow the use of this innovative drug class in clinical routine for treating these patients.

Study Question:

We aimed at further clarifying the role of SGLT2i in patients with diagnosis of HF, capitalizing on pooled sample size and heightened power for clinically relevant safety and efficacy outcomes.

Data Sources:

We conducted a systematic search of PubMed, reference lists of relevant articles, and Medline database from inception until March 1, 2021.

Study Design:

This meta-analysis was completed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched for randomized trials that evaluated the cardiovascular effects of SGLT2i in patients with HF. Three investigators independently assessed study eligibility, extracted the data, and assessed risk of bias. Hazard ratios and 95% confidence intervals (CIs) were pooled and meta-analyzed using a random-effect model. Numbers needed to treat (NNT) with the relative 95% CIs were also calculated. The primary outcome was a composite of HF hospitalization or an urgent visit for worsening HF and cardiovascular death.

Results:

Three trials were included in the study. Overall, treatment with SGLT2i was associated with a lower risk of the primary composite outcome [hazard ratios 0.73, 95% CI (0.67–0.80), NNT = 11.3]. Similarly, there was a significantly reduced risk of cardiovascular death, all-cause death, HF hospitalization and need for urgent treatment for HF, and HF hospitalization.

Conclusions:

Therefore, the available evidence supports the routine use of these drugs as standard-of-care, also given the highly favorable NNTs.
The role of fungus in the pathogenesis of chronic rhinosinusitis
Authors: Challapalli Sai D. , McKee Sean , Luong Amber U.
Published: December 2021

Purpose of review

The etiologic role of fungi in chronic rhinosinusitis remains controversial. The purpose of this review is to further our understanding of molecular immunologic pathways activated by fungi and clinical trials of antifungals in severe subtypes of asthma and allergic fungal rhinosinusitis.

Recent findings

Various fungal components such as protease and chitin are capable of eliciting a type 2 innate and adaptive immune response. However, definitive studies on the etiologic role of fungi in chronic rhinosinusitis (CRS) is dependent on the development of a fungi-induced murine model of CRS. Short of this model, extrapolations of observations and results from clinical trials in fungi-induced asthma subtypes support a key role of fungi in the pathophysiology of allergic fungal rhinosinusitis and possibly other CRS endotypes.

Fungi plays a key role in the pathophysiology of several subtypes of chronic inflammatory respiratory diseases. However, a fungi-induced murine model of CRS is needed to explicitly investigate the molecular pathways and potential therapeutic targets.
Two Histologic Patterns of Lymphomatoid Papulosis Occurring in a Child: A Matter of Timing?
Authors: Shi Ruoyu , Koh Mark Jean-Aan
Published: December 2021

There are several histologic patterns seen in lymphomatoid papulosis, with the possibility of different subtypes occurring in the same patient. We report a case of lymphomatoid papulosis presenting with 2 histologic subtypes (types A and B) occurring concomitantly in a 10-year-old child, and postulate that the different subtypes occur dependent on the age of the lesion biopsied. Incidentally, one of the biopsies also shows a rarely seen pattern of pseudoepitheliomatous hyperplasia in a pediatric lymphomatoid papulosis patient.
Undifferentiated and Unresectable Sarcoma With NTRK3-Fusion in a Pediatric Patient Treated With Larotrectinib and Proton Beam Radiotherapy
Authors: Olsen Mallery R. , Denu Ryan A. , Lyon Jane B. , Gulliver Jessica M. , Capitini Christian M. , DeSantes Kenneth B.
Published: December 2021

A 6-year-old female presenting with an abdominal mass was found to have an unresectable undifferentiated sarcoma. The tumor did not respond to multiagent chemotherapy. However, molecular testing identified an NTRK3-fusion, and treatment was changed to larotrectinib monotherapy. Following 6 months of therapy, the patient achieved a very good partial response with 96% reduction in tumor size. She underwent proton beam radiation therapy with continued larotrectinib therapy and achieved a complete response. This case report shows that an NTRK fusion positive undifferentiated sarcoma can be safely treated with larotrectinib and radiation therapy and highlights the importance of early molecular testing.
Large Anterior Mediastinal Mass and Cardiac Infiltration at Diagnosis in a Child With T-cell Acute Lymphoblastic Leukemia
Authors: Meyer Erin J. , Umaretiya Puja , Vrooman Lynda M.
Published: December 2021

While anterior mediastinal masses are a common presenting feature of T-cell acute lymphoblastic leukemia, cardiac leukemic infiltration is an exceedingly rare extramedullary manifestation. We report a 4-year-old female with new-onset T-cell acute lymphoblastic leukemia who was found to have a large interventricular septal mass upon initial presentation. This patient required a unique management approach with serial echocardiograms, continuous telemetry, and hemodynamic monitoring with close surveillance for ventricular ectopy. Given a good response to traditional leukemia therapy, the cardiac mass was presumed to have been a focal infiltrate of leukemic cells.
Ultrasound-assisted Lumbar Puncture for Obese Pediatric Oncology Patients: A Feasibility Study
Authors: Leviter Julie , Kadan-Lottick Nina S. , Auerbach Claudia , Riera Antonio
Published: December 2021

Lumbar punctures (LPs) are performed frequently on children with leukemia and lymphoma as part of the standard of care. They are typically performed by pediatric oncology providers for both diagnostic and therapeutic interventions with the aid of moderate or deep sedation. Point-of-Care Ultrasound (POCUS) has emerged as a promising strategy to aid in LP procedures and has been found to be associated with lower number of attempts, and higher success rates. We describe our experience using POCUS to assist with LPs in a subgroup of pediatric oncology patients identified to be procedurally difficult secondary to obesity. This collaboration was well received and resulted in successful LPs in most (8/9) cases. This is a promising modality to improve the delivery of care and LP success in pediatric oncology patients.
Recent concepts in fungal involvement in skin and soft tissue infections
Authors: Peghin Maddalena , Ruiz-Camps Isabel
Published: December 2021

As the at-risk population expands and new antifungal resistance patterns develop, it is critical to understand and recognize cutaneous manifestations of old and emerging fungal diseases.

Purpose of review

The aim of this review is to provide an overview of the most frequent and emerging deep cutaneous fungal infections following either primary inoculation or secondary spread after haematogenous seeding in disseminated infections in different geographical areas.

Recent findings

Fungal skin and soft tissue infections (SSTIs) encompass a variety of pathological conditions based on the site of the infection, route of acquisition of the pathogen, epidemiological setting and the virulence of the fungus in relation to the host. The approach to a patient suspected of having a fungal SSTI is complex and usually poses a major diagnostic challenge. The treatment approach should include attempts at immune reconstitution, targeted antifungal therapy and/or aggressive surgical debridement.

Fungal SSTIs can be an important cause of morbidity and mortality in both immunocompromised and immunocompetent patients and are being reported with increasing frequency worldwide.
Impaired Color Discrimination in Alzheimer Disease Dementia
Authors: Boedeker Sebastian , Halstenberg Eileen , Schulz Philipp , Beblo Thomas , Kreisel Stefan , Driessen Martin , Toepper Max
Published: December 2021

Objective:

Patients with Alzheimer disease dementia (ADD) often show impaired orientation and navigation. Signage offers an opportunity to compensate for these deficits, communicate information efficiently and facilitate wayfinding. Certain properties of signs such as colors and contrasts may beneficially affect the uptake and processing of information particularly in ADD patients.

Methods:

Thirty-six healthy older adults and 30 ADD patients performed a computerized color perception task that required discriminating different color combinations. The effects of different contrast features on performance accuracy and speed in the 2 experimental groups were examined by nonparametric mixed analysis of variances.

Results:

Analyses revealed a significant effect of contrast polarity on reaction times, significant effects of group on reaction times and errors as well as a marginally significant interaction of group×color on errors. All participants benefitted from positive contrast polarity (ie, dark target on lighter background) as indicated by increased performance speed. Furthermore, ADD patients reacted slower and less accurate than healthy controls, but showed higher accuracy at black-white and red-yellow than at blue-green color combinations.

Conclusions:

Our findings suggest the implementation of signs with positive contrast polarity to ensure faster reactions. In addition, certain color combinations may enhance accuracy, particularly in patients with ADD.
Hand hygiene among nurses in pediatric blood and marrow transplantation setting: a best practice implementation project
Authors: Nedelcu Viorica , Niculiţă Oana O. , Toporaş Elena , Zazu Mariana , Mazilu Doina C. , Jiménez Marina Gallego , Grinţescu loana M.
Published: December 2021

Objectives:

The aim of this project was to promote evidence-based best practice regarding hand hygiene among nurses in a pediatric blood and marrow transplantation (BMT) setting.

Introduction:

Healthcare-associated infections (HAI) represent important complications of healthcare with potentially major impact on patient outcomes. Most HAI are transmitted through the hands of healthcare professionals (HCP) and therefore hand hygiene is the simplest, most effective and proven method for preventing HAI. However, the overall compliance rate of HCP with hand hygiene remains at a very low level. In this case, it is necessary to implement strategies to improve the compliance with hand hygiene of the HCP with the purpose of reducing HAI rates, mortality and costs, all the more so as it is known that patients with BMT have an increased risk of HAI.

Methods:

This best practice implementation project was based on the JBI methodological approach and included three phases of activity: a baseline audit, implementation of strategies and a follow-up audit. The project was conducted in the pediatric BMT setting of a large university hospital located in Bucharest, Romania, and the sample included 10 nurses and five relatives of pediatric patients from this ward.

Results:

As a result of the implementation of strategies, improvements were observed across seven audit criteria, given that for two audit criteria out of a total of nine audit criteria compliance was maximum (100%) since the baseline phase. Moreover, the post implementation audit showed a complete compliance (100%) for six audit criteria. However, for the other three audit criteria the compliance in follow-up audit was high: 92, 85 and 80%, respectively.

Conclusion:

The strategies applied within this evidence implementation project were appropriate, so the project was a success. However, permanent actions are required to sustain changes in practice and improvements made.
Performance of genetic imputation across commercial crop species
Authors: Thorn Steve , Whalen Andrew , Kollers Sonja , Gholami Mahmood , da Silva Helena Sofia , Wimmer Valentin , Hickey John M
Published: December 2021

We show that accurate imputation can be carried out in three commercial plant species (maize, sugar beet and wheat) and that accurate imputation does not require a pedigree, although pedigree information can improve accuracy and speed. Our approach uses a hidden Markov model to build a haplotype library from individuals genotyped at high-density and then uses this library to impute low-density genotyped individuals to high-density. To build the library, we use founders when the pedigree is known, or a sample of progeny when the pedigree is unknown. Without a pedigree, and with 50 individuals genotyped at high-density and 100 low-density markers per chromosome, the median accuracies were 0.97 (maize), 0.96 (sugar beet), and 0.94 (wheat). We obtained similar accuracies with a pedigree. For biparental crosses with 100 markers per chromosome, median accuracies were 0.96 (maize), 0.96 (sugar beet) and 0.94 (wheat). For the imputation scenarios without a pedigree, we compared accuracies with those obtained by running Beagle 5.1. In all but one scenario, our method outperformed Beagle. We believe that plant breeders can effectively apply imputation in many crop species.
PEPPI: Whole-proteome protein-protein interaction prediction through structure and sequence similarity, functional association, and machine learning
Authors: Bell Eric W. , Schwartz Jacob H. , Freddolino Peter L. , Zhang Yang
Published: December 2021

Proteome-wide identification of protein-protein interactions is a formidable task which has yet to be sufficiently addressed by experimental methodologies. Many computational methods have been developed to predict proteome-wide interaction networks, but few leverage both the sensitivity of structural information and the wide availability of sequence data. We present PEPPI, a pipeline which integrates structural similarity, sequence similarity, functional association data, and machine learning-based classification through a naïve Bayesian classifier model to accurately predict protein-protein interactions at a proteomic scale. Through benchmarking against a set of 798 ground truth interactions and an equal number of noninteractions, we have found that PEPPI attains 4.5% higher AUROC than the best of other state-of-the-art methods. As a proteomic-scale application, PEPPI was applied to model the interactions which occur between SARS-CoV-2 and human host cells during coronavirus infection, where 403 high-confidence interactions were identified with predictions covering 73% of a gold standard dataset from PSICQUIC and demonstrating significant complementarity with the most recent high-throughput experiments. PEPPI is available both as a webserver and in a standalone version and should be a powerful and generally applicable tool for computational screening of protein-protein interactions.
SARS-CoV-2 wildlife surveillance in Ontario and Québec, Canada
Authors: Greenhorn Janet E. , Kotwa Jonathon D. , Bowman Jeff , Bruce Laura , Buchanan Tore , Buck Peter A. , Dibernardo Antonia , Flockhart Logan , Gagnier Marianne , Hou Aaron , Jardine Claire M. , Lair Stephane , Lindsay L. Robbin , Masse Ariane , Muchaal Pia K. , Nituch Larissa A. , Sotto Angelo , Stevens Brian , Yip Lily , Mubareka Samira
Published: December 2021

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic, is capable of infecting a variety of wildlife species. Wildlife living in close contact with humans are at an increased risk of SARS-CoV-2 exposure and if infected have the potential to become a reservoir for the pathogen, making control and management more difficult.

Objective

To conduct SARS-CoV-2 surveillance in urban wildlife from Ontario and Québec, Canada, increasing our knowledge of the epidemiology of the virus and our chances of detecting spillover from humans into wildlife.

Methods

Using a One Health approach, we leveraged activities of existing research, surveillance, and rehabilitation programs among multiple agencies to collect samples from 776 animals from 17 different wildlife species between June 2020 and May 2021. Samples from all animals were tested for the presence of SARS-CoV-2 viral RNA, and a subset of samples from 219 animals across 3 species (raccoons, Procyon lotor; striped skunks, Mephitis mephitis; and mink, Neovison vison) were also tested for the presence of neutralizing antibodies.

Results

No evidence of SARS-CoV-2 viral RNA or neutralizing antibodies was detected in any of the tested samples.

Conclusion

Although we were unable to identify positive SARS-CoV-2 cases in wildlife, continued research and surveillance activities are critical to better understand the rapidly changing landscape of susceptible animal species. Collaboration between academic, public and animal health sectors should include experts from relevant fields to build coordinated surveillance and response capacity.
Investigating the human host - ssRNA virus interaction landscape using the SMEAGOL toolbox
Authors: Lal Avantika , Ferrarini Mariana Galvao , Gruber Andreas J.
Published: December 2021

Viruses are intracellular parasites that need their host cell to reproduce. Consequently, they have evolved numerous mechanisms to exploit the molecular machinery of their host cells, including the broad spectrum of host RNA-binding proteins (RBPs). However, the RBP interactome of viral genomes and the consequences of these interactions for infection are still to be mapped for most RNA viruses. To facilitate these efforts we have developed SMEAGOL, a fast and user-friendly toolbox to analyze the enrichment or depletion of RBP binding motifs across RNA sequences (https://github.com/gruber-sciencelab/SMEAGOL). To shed light on the interaction landscape of RNA viruses with human host cell RBPs at a large scale, we applied SMEAGOL to 197 single-stranded RNA (ssRNA) viral genome sequences. We find that the majority of ssRNA virus genomes are significantly enriched or depleted in binding motifs for human RBPs, suggesting selection pressure on these interactions. Our analysis provides an overview of potential virus - RBP interactions, covering the majority of ssRNA viral genomes fully sequenced to date, and represents a rich resource for studying host interactions vital to the virulence of ssRNA viruses. Our resource and the SMEAGOL toolbox will support future studies of virus / host interactions, ultimately feeding into better treatments.
CRSIPR-A-I: a webtool for the efficacy prediction of CRISPR activation and interference
Authors: Zheng Xiao , Cui Jiajun , Wang Yixuan , Zhang Jing , Wang Chaochen
Published: December 2021

Abstract

CRISPR-based gene activation (CRISPRa) or interference (CRISPRi) are powerful and easy-to-use approaches to modify the transcription of endogenous genes in eukaryotes. Successful CRISPRa/i requires sgRNA binding and alteration of local chromatin structure, hence largely depends on the original epigenetic status of the target. Consequently, the efficacy of the CRISPRa/i varies in a wide range when applied to target different gene loci, while a reliable prediction tool is unavailable. To address this problem, we integrated published single cell RNA-Seq data involved CRISPRa/i and epigenomic profiles from K562 cells, identified the significant epigenetic features contributing to CRISPRa/i efficacy by ranking the weight of each feature. We further established a mathematic model and built a user-friendly webtool to predict the CRISPRa/i efficacy of customer-designed sgRNA in different cells. Moreover, we experimentally validated our model by employing CROP-Seq assays. Our work provides both the epigenetic insights into CRISPRa/i and an effective tool for the users.
Omicron and Delta Variant of SARS-CoV-2: A Comparative Computational Study of Spike protein
Authors: Kumar Suresh , Thambiraja Thiviya S. , Karuppanan Kalimuthu , Subramaniam Gunasekaran
Published: December 2021

Emerging SARS-CoV-2 variants, especially those of concern, may have an impact on the virus’s transmissibility and pathogenicity, as well as diagnostic equipment performance and vaccine effectiveness. Even though the SARS-CoV-2 Delta variant (B.1.617.2) emerged during India’s second wave of infections, Delta variants have grown dominant internationally and are still evolving. On November 26, 2021, WHO identified the variant B.1.1.529 as a variant of concern, naming it Omicron, based on evidence that Omicron contains numerous mutations that may influence its behaviour. However, the mode of transmission and severity of the Omicron variant remains unknown. We used computational studies to examine the Delta and Omicron variants in this work and found that the Omicron variant had a higher affinity for human ACE2 than the Delta variant due to a significant number of mutations in the SARS-CoV-2 receptor binding domain, indicating a higher potential for transmission. Based on docking studies, the Q493R, N501Y, S371L, S373P, S375F, Q498R, and T478K mutations contribute significantly to high binding affinity with human ACE2. In comparison to the Delta variant, both the entire spike protein and the RBD in Omicron include a high proportion of hydrophobic amino acids such as leucine and phenylalanine. These amino acids are located within the protein’s core and are required for structural stability. Omicron has a higher percentage of alpha-helix structure than the Delta variant in both whole spike protein and RBD, indicating that it has a more stable structure. We observed a disorder-order transition in the Omicron variant between spike protein RBD regions 468-473, and it may be significant in the influence of disordered residues/regions on spike protein stability and binding to ACE2. A future study might investigate the epidemiological and biological consequences of the Omicron variant.
VExD: A curated resource for human gene expression alterations following viral infection
Authors: Dexheimer Phillip J , Pujato Mario , Roskin Krishna , Weirauch Matthew T
Published: December 2021

Much of the host antiviral response is mediated through changes to host gene expression levels. Likewise, viruses induce changes to host gene expression levels in order to promote the viral life cycle and evade the host immune system. However, there is no resource that specifically collects human gene expression levels pre- and post-virus infection. Further, public gene expression repositories do not contain enough specialized metadata to easily find relevant experiments. Here, we present the Virus Expression Database (VExD), a freely available web site and database that collects human gene expression datasets in response to viral infection. VExD contains ∼8,000 uniformly processed samples obtained from 289 studies examining 51 distinct human viruses. We show that the VExD processing pipeline preserves known antiviral responses in the form of interferon-stimulated genes. We further show that the datasets collected in VExD can be used to quickly identify supporting data for experiments performed in human cells or model organisms. VExD is freely available athttps://vexd.cchmc.org/.
Secreted ORF8 is a pathogenic cause of severe COVID-19 and is potentially targetable with select NLRP3 inhibitors
Authors: Wu Xiaosheng , Manske Michelle K. , Ruan Gordon J. , Witter Taylor L. , Nowakowski Kevin E. , Abeykoon Jithma P. , Tang Xinyi , Yu Yue , Gwin Kimberly A. , Wu Annie , Taupin Vanessa , Bhardwaj Vaishali , Paludo Jonas , Dasari Surendra , Dong Haidong , Ansell Stephen M. , Badley Andrew D. , Schellenberg Matthew J. , Witzig Thomas E.
Published: December 2021

COVID-19 is a significant cause of morbidity and mortality in blood cancer patients, especially those on immunosuppressive therapy. Despite extensive research, the specific factor associated with SARS-CoV-2 infection that mediates the life-threatening inflammatory cytokine response in patients with severe COVID-19 remains unidentified. Herein we demonstrate that the virus-encoded Open Reading Frame 8 (ORF8) protein is abundantly secreted as a glycoprotein in vitro and in symptomatic patients with COVID-19. ORF8 specifically binds to the NOD-like receptor family pyrin domain-containing 3 (NLRP3) in CD14+ monocytes to induce a non-canonical inflammasomal response, and a canonical response when the second activation signal is present. Levels of ORF8 protein in the blood correlate with severity and disease-specific mortality in patients with acute SARS-CoV-2 infection. Furthermore, the ORF8-induced inflammasome response was readily inhibited by the NLRP3 inhibitor MCC950 in vitro. Our study identifies a dominant cause of pathogenesis, its underlying mechanism, and a potential new treatment for severe COVID-19.

Key points

Secreted glycoprotein ORF8 induces monocytic pro-inflammatory cytokines involving the activation of the NLPR3 inflammasome pathway.

ORF8 is prognostically present in the blood of symptomatic patients with covid-19 and is targetable with NLRP3 inhibitor MCC-950.
ImaGene: A web-based software platform for tumor radiogenomic evaluation and reporting
Authors: Sukhadia Shrey S. , Tyagi Aayush , Venkataraman Vivek , Mukherjee Pritam , Prathosh AP , Divate Mayur D. , Gevaert Olivier , Nagaraj Shivashankar H.
Published: December 2021

The field of radiomics has undergone several advancements in approaches to uncovering hidden quantitative features from tumor imaging data for use in guiding clinical decision-making for cancer patients. Radiographic imaging techniques provide insight into the imaging features of tumor regions of interest (ROIs), while immunohistochemistry and sequencing techniques performed on biopsy samples yield omics data. Potential associations between tumor genotype and phenotype can be identified from imaging and omics data via traditional correlation analysis, as well as through artificial intelligence (AI) models. However, at present the radiogenomics community lacks a unified software platform for which to conduct such analyses in a reproducible manner.

To address this gap, we propose ImaGene, a web-based platform that takes tumor omics and imaging data sets as input, performs correlation analysis between them, and constructs AI models (optionally using only those features found to exhibit statistically significant correlation with some element of the opposing dataset). ImaGene has several modifiable configuration parameters, providing users complete control over their analysis. For each run, ImaGene produces a comprehensive report displaying a number of intuitive model diagnostics.

To demonstrate the utility of ImaGene,exploratory studies surrounding Invasive Breast Carcinoma (IBC) and Head and Neck Squamous Cell Carcinoma (HNSCC) on datasets acquired from public databases are conducted. Potential associations are identified between several imaging features and 6 genes: CRABP1, SMTNL2, FABP1, HAS1, FAM163A and DSG1 for IBC, and 4 genes: CEACAM6, NANOG, ACSM2B, and UPK2 for HNSCC.

In summary, the software provides researchers with a transparent tool for which to begin radiogenomic analysis and explore possible further directions in their research. We anticipate that ImaGenewill become the standard platform for tumor analyses in the field of radiogenomics due to its ease of use, flexibility, and reproducibility, and that it can serve as an enabling centrepoint for an emerging radiogenomic knowledge base.
High viral loads: what drives fatal cases of COVID-19 in vaccinees? – an autopsy study
Authors: Hirschbühl Klaus , Schaller Tina , Märkl Bruno , Claus Rainer , Sipos Eva , Rentschler Lukas , Maccagno Andrea , Grosser Bianca , Kling Elisabeth , Neidig Michael , Kröncke Thomas , Spring Oliver , Braun Georg , Bösmüller Hans , Seidl Maximilian , Esposito Irene , Pablik Jessica , Hilsenbeck Julia , Boor Peter , Beer Martin , Dintner Sebastian , Wylezich Claudia
Published: December 2021

Background

The rate of SARS-CoV-2 breakthrough infections in vaccinees is becoming an increasingly serious issue.

Objective

To determine the causes of death, histological organ alteration, and viral spread in relation to demographic, clinical-pathological, viral variants, and vaccine types.

Design

Comprehensive retrospective observational cohort study. Setting: Consecutive cases from four German academic medical centers.

Patients

Deceased with proven SARS-CoV-2 infection after vaccination who died between January and November 2021. Collections of 29 vaccinees which were analyzed and compared to 141 nonvaccinated control cases.

Results

Autopsies were performed on 16 partially and 13 fully vaccinated individuals. Most patients were elderly and suffered from several relevant comorbidities. Real-time RT-PCR (RT-qPCR) identified a significantly increased rate of generalized viral dissemination within the organism in vaccinated cases versus nonvaccinated cases (45% vs. 16%, respectively; P = 0.008). Vaccinated cases also showed high viral loads, reaching Ct values below 10, especially in the upper airways and lungs. This was accompanied by high rates of pulmonal bacterial or mycotic superinfections and the occurrence of immunocompromising factors such as malignancies, immunosuppressive drug intake, or decreased immunoglobulin levels. All these findings were particularly accentuated in partially vaccinated patients compared to fully vaccinated individuals. A fatal course after vaccination occurred in only 14% of all COVID-19 deceased in Augsburg.

Limitations

Restricted number of cases

Conclusions

Fatal cases of COVID-19 in vaccinees were rare and often associated with severe comorbidities or other immunosuppressive conditions. Interestingly, we observed striking virus dissemination in our case study, which may indicate a decreased ability to eliminate the virus in patients with an impaired immune system. However, the potential role of antibody-dependent enhancement must also be ruled out in future studies.

Funding source

This work was supported by the German Registry of COVID-19 Autopsies (www.DeRegCOVID.ukaachen.de) and funded by the Federal Ministry of Health (ZMVI1-2520COR201), the Federal Ministry of Education and Research within the framework of the network of university medicine (DEFEAT PANDEMICs, 01KX2021), and the German Federal Ministry of Food and Agriculture through the Federal Office for Agriculture and Food (project ZooSeq, grant number 2819114019).