bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of Proteinase-activated Receptor 2 (PAR2) as a Correlate of Concern in Triple-negative Breast Cancer (TNBC)
Authors: Kapatia Gargi , Kaur Subhpreet , Kumar Sandeep , Laroiya Ishita , Singh Gurpreet , Sharma Maryada , Bal Amanjit , Luthra-Guptasarma Manni
Published: March 2022

Purpose:

Triple-negative breast cancer (TNBC), a highly aggressive cancer with poor outcome and lacking specific diagnostic, prognostic, or targeted therapeutic strategies, constitutes roughly 20% of all breast cancer cases. TNBC cells lack receptors for estrogen, progesterone, and human epidermal growth factor. The effort continues to find a suitable correlate that could serve as a TNBC biomarker, or as therapeutic target, or both.

Materials and Methods:

A retrospective study was performed with 88 TNBC and 74 non-TNBC patients who had undergone mastectomy/lumpectomy with axillary clearance for carcinoma breast. Immunohistochemical staining was carried out for levels of proteinase-activated receptor 2 (PAR2), encoded by F2RL1 gene, and staining scores were calculated, based on intensity and percentage positivity.

Results:

PAR2 levels were markedly upregulated in TNBC patients, compared with patients with other breast cancer subtypes. Amongst different non-TNBC subtypes, higher expression was noted in luminal B (88.8%) and HER2+ (100%), compared with luminal A (52.5%). PAR2 levels were significantly high in TNBC patients with age more than 40 years than corresponding patients of non-TNBC group (P=0.0017). Furthermore, there was a statistically significant increase in levels of PAR2 expression in lymph node negative (P=0.0096) and early stage (P=0.005) of TNBC versus non-TNBC patients. PAR2 staining of ductal carcinoma in situ and invasive ductal carcinoma revealed lower expression in invasive component.

Conclusions:

Our data suggest that PAR2 levels constitute a correlate of concern for TNBC, tying in with a recent report that higher levels of F2RL1 gene expression correlate with poorer disease-free, as well as overall survival in TNBCs.
Attempting to Solve the Pigmented Epithelioid Melanocytoma (PEM) Conundrum
Authors: de la Fouchardiere Arnaud , Tirode Franck , Castillo Christine , Buisson Adrien , Boivin Felix , Macagno Nicolas , Pissaloux Daniel
Published: March 2022

Pigmented epithelioid melanocytoma is a rare cutaneous melanocytic proliferation considered high-grade melanocytoma in the 2018 WHO Classification of Skin Tumors. Little has been reported about the associated genetic drivers in addition to BRAF and MAP2K1 mutations or PRKCA gene fusions. Here, we present a series of 21 cases of PRKAR1A-inactivated melanocytic tumors in which we could assess the associated genetic background. We identified 9 different driver genes related to the common, Spitz, blue nevi, and PRKC-fused groups. Nine cases were associated with a canonical BRAF p.V600E mutation, a hallmark of the common nevus group. They occurred mainly in young adults. All were combined (biphenotypic) cases with a variable proportion of compound nevus. The pigmented epithelioid melanocytoma component was made of thin fascicules or isolated epithelioid cells covered by a dense hyperpigmented melanophage background and was predominantly located in the upper dermis. One such case was malignant. Six cases were associated with Spitz-related genetic anomalies ranging from HRAS or MAP2K1 mutations to gene fusions involving MAP3K8, MAP3K3, and RET. They occurred mainly in children and young adults. Morphologically, they showed large confluent junctional nests in a hyperplastic epidermis and a fascicular dermal component of spindled and epithelioid melanocytes with a frequent wedged silhouette. Intravascular invasion was observed in 4/6 cases. Five cases were associated with canonical mutations of the blue nevus group with 4 CYSLTR2 p.L129Q and 1 GNAQ p.Q209L mutations. They were removed mainly in adults and showed a frequent junctional component with epidermal hyperplasia. The dermal component showed dense fascicules of spindled and epithelioid melanocytes predominating over melanophages. One case occurred in a PRKCA-fused tumor in an adolescent with classic morphologic features. These results could potentially shift the concept of PRKAR1A-inactivated melanocytoma, changing from a rather unified model to a more complex one, including genetic subgroup variations with clinical and morphologic specificities. The genetic background of PRKAR1A-inactivated melanocytic tumors should be systematically explored to better understand the extent and clinical behavior of these complex lesions.
Diffuse and Localized SARS-CoV-2 Placentitis
Authors: Redline Raymond W. , Ravishankar Sanjita , Bagby Christina , Saab Shahrazad , Zarei Shabnam
Published: March 2022

Coronavirus disease 2019 (COVID-19) infection in pregnancy has been associated with preterm delivery and preeclampsia. A less frequent and underrecognized complication is extensive placental infection which is associated with high rates of perinatal morbidity and mortality. The frequency, early pathogenesis, and range of lesions associated with this infection are poorly understood. We conducted a population-based study of placental pathology from all mothers with COVID-19 (n=271) over an 18-month period delivering within our health system. The overall prevalence of diffuse severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) placentitis, as defined by typical histology and immunohistochemical (IHC) staining for SARS-CoV-2 spike protein, was 14.8/1000, but increased to 59/1000 in preterm births. We also identified 3 cases with isolated small foci of localized SARS-CoV-2 placentitis, characterized by focal perivillous fibrin and intervillositis, which illustrate the early pathogenesis and suggest that infection may be contained in some cases. Two other placental lesions were more common in mothers with COVID-19, high-grade maternal vascular malperfusion in preterm deliveries and high-grade chronic villitis at term (5/5 cases tested of the latter were negative by IHC for SARS-CoV-2). Additional investigation of diffuse and localized SARS-CoV-2 placentitis by IHC showed loss of BCL-2, C4d staining in surrounding villi, and an early neutrophil-predominant intervillous infiltrate that later became dominated by monocyte-macrophages. We propose a model of focal infection of syncytiotrophoblast by virally infected maternal leukocytes leading to loss of BCL-2 and apoptosis. Infection is then either contained by surrounding fibrinoid (localized) or initiates waves of aponecrosis and immune activation that spread throughout the villous parenchyma (diffuse).
Vasculitis in Patients With Sarcoidosis
Authors: Kimbrough Bradly A. , Warrington Kenneth J. , Langenfeld Hannah E. , Crowson Cynthia S. , Carmona Eva M. , Virata Andrew R. , Koster Matthew J.
Published: March 2022

Objectives

Vasculitis in patients with sarcoidosis is rare and can affect any sized blood vessel. Limited information describing this association is available.

Methods

A single-institution medical records review study was performed reviewing all patients with a diagnosis code for sarcoidosis and vasculitis between January 1, 1998, and December 31, 2019. Data were abstracted regarding diagnosis, treatment, and outcomes from medical records. Patients were diagnosed with vasculitis based on biopsy and/or arterial imaging. Comparison between patients presenting with large and/or medium vessel vasculitis (L/MVV) versus patients with only small vessel vasculitis (SVV) was performed.

Results

Seventeen patients were identified during the study period. Nine patients (56% female) had L/MVV, and 8 (50% female) had SVV. Sarcoidosis preceded vasculitis in 4 (44%) L/MVV and 3 (38%) SVV. The mean ± SD age at sarcoidosis diagnosis was 53.2 ± 17.8 and 51.9 ± 11.4 years, and the mean ± SD age at vasculitis diagnosis was 57.4 ± 19.6 and 59.0 ± 13.4 years in L/MVV and SVV, respectively. Number of organ systems involved by sarcoidosis was similar (median [interquartile range], 3 [1–4] L/MVV vs 2.5 [1.75–3.25] SVV). The mean length of follow-up was 11.5 ± 12.8 in L/MVV and 13.1 ± 14.3 years in SVV. Complete response to therapy for vasculitis was observed in 8 of 9 with L/MVV and 7 of 8 with SVV. Four patients with SVV were able to stop all immunosuppression as compared with only 1 patient with L/MVV at the last follow-up.

Conclusions

This series observed a comparable number of patients with L/MVV and SVV. Although a variety of treatments were used, most patients achieved remission regardless of vessel size affected. Clinicians should be aware of the overlap between sarcoidosis and vasculitis.
Interrater Reliability, Acceptability, and Practicality of Real-Time Video Pediatric Gait, Arms, Legs, and Spine for Musculoskeletal Assessment of Children During Telemedicine Visits
Authors: Giray Esra , Kenis-Coskun Ozge , Karadag-Saygi Evrim , Ozyemisci-Taskiran Ozden
Published: March 2022

Background/Objective

With the COVID-19 (coronavirus disease 2019) pandemic, telemedicine applications gained momentum, and clinicians tried to develop various musculoskeletal examination methods to be used in telemedicine visits. The aim of this study is to investigate the interrater reliability, acceptability, and practicality of the real-time video Pediatric Gait, Arms, Legs, and Spine (v-pGALS) assessment used in the evaluation during the telemedicine visit.

Methods

The study was designed as cross-sectional. Twenty school-aged children who presented to outpatient clinics with musculoskeletal complaints were included. For interrater reliability, the children were evaluated by face-to-face examination with v-pGALS, and then the child was reevaluated by another physiatrist with real-time evaluation (online video call) with the help of a parent. For acceptability, the time taken and the discomfort caused were evaluated by patients/parents with the smiley face visual analog scale, whereas to assess practicality, the ratio of completeness to duration of examination completion was recorded.

Results

κ coefficient of the agreement was found to be 0.88 between the results of the face-to-face examination and online video examination, suggesting very good agreement between the 2 raters. Acceptability of v-pGALS by parents and patients was high; 60% of children and 80% of parents found the duration of examination acceptable, and 70% of the patients and 95% of parents reported no discomfort caused by examination. The duration of face-to-face examination was 5.75 ± 1.29 minutes, whereas the duration of online examination was 15.81 ± 4.9 minutes.

Conclusions

Video pGALS is a reliable, acceptable, and practical examination system that can be used for musculoskeletal assessment of children in telemedicine visits.
Coronary Computed Tomography Angiography-Based Calcium Scoring
Authors: Emrich Tilman , Aquino Gilberto , Schoepf U. Joseph , Braun Franziska M. , Risch Franka , Bette Stefanie J. , Woznicki Piotr , Decker Josua A. , O’Doherty Jim , Brandt Verena , Allmendinger Thomas , Nowak Tristan , Schmidt Bernhard , Flohr Thomas , Kroencke Thomas J. , Scheurig-Muenkler Christian , Varga-Szemes Akos , Schwarz Florian
Published: March 2022

Purpose

The aim of this study was to evaluate coronary computed tomography angiography (CCTA)-based in vitro and in vivo coronary artery calcium scoring (CACS) using a novel virtual noniodine reconstruction (PureCalcium) on a clinical first-generation photon-counting detector–computed tomography system compared with virtual noncontrast (VNC) reconstructions and true noncontrast (TNC) acquisitions.

Materials and Methods

Although CACS and CCTA are well-established techniques for the assessment of coronary artery disease, they are complementary acquisitions, translating into increased scan time and patient radiation dose. Hence, accurate CACS derived from a single CCTA acquisition would be highly desirable. In this study, CACS based on PureCalcium, VNC, and TNC, reconstructions was evaluated in a CACS phantom and in 67 patients (70 [59/80] years, 58.2% male) undergoing CCTA on a first-generation photon counting detector–computed tomography system. Coronary artery calcium scores were quantified for the 3 reconstructions and compared using Wilcoxon test. Agreement was evaluated by Pearson and Spearman correlation and Bland-Altman analysis. Classification of coronary artery calcium score categories (0, 1–10, 11–100, 101–400, and >400) was compared using Cohen κ.

Results

Phantom studies demonstrated strong agreement between CACSPureCalcium and CACSTNC (60.7 ± 90.6 vs 67.3 ± 88.3, P = 0.01, r = 0.98, intraclass correlation [ICC] = 0.98; mean bias, 6.6; limits of agreement [LoA], −39.8/26.6), whereas CACSVNC showed a significant underestimation (42.4 ± 75.3 vs 67.3 ± 88.3, P < 0.001, r = 0.94, ICC = 0.89; mean bias, 24.9; LoA, −87.1/37.2). In vivo comparison confirmed a high correlation but revealed an underestimation of CACSPureCalcium (169.3 [0.7/969.4] vs 232.2 [26.5/1112.2], P < 0.001, r = 0.97, ICC = 0.98; mean bias, −113.5; LoA, −470.2/243.2). In comparison, CACSVNC showed a similarly high correlation, but a substantially larger underestimation (24.3 [0/272.3] vs 232.2 [26.5/1112.2], P < 0.001, r = 0.97, ICC = 0.54; mean bias, −551.6; LoA, −2037.5/934.4). CACSPureCalcium showed superior agreement of CACS classification (κ = 0.88) than CACSVNC (κ = 0.60).

Conclusions

The accuracy of CACS quantification and classification based on PureCalcium reconstructions of CCTA outperforms CACS derived from VNC reconstructions.
In-hospital outcomes of intercostal nerve cryoablation and surgical stabilization of rib fractures
Authors: Fernandez Carlos A. , Narveson Joel R. , Niu Fang , Norton Elizabeth , Brown Emily C. , Punja Viren , Veatch Jessica M. , Capasso Thomas , Patel Neil D. , Ewing Kaily , Kuncir Eric
Published: March 2022

BACKGROUND

Severe pain and pulmonary complications commonly follow rib fractures, both of which may be improved by surgical stabilization of rib fractures (SSRFs). However, significant postoperative pain still persists which may negatively impact in-hospital outcomes. Combining intercostal nerve cryoablation (INCA) with SSRF may improve those outcomes by further decreasing postoperative pain, opioid consumption, and pulmonary complications. The hypothesis is that INCA plus SSRF reduces opioids consumption compared with SSRF alone.

METHODS

The retrospective analysis included trauma patients 18 years or older who underwent SSRF, with or without INCA, in a Level I trauma center between 2015 and 2021. Patients received INCA at the surgeons' discretion based on familiarity with the procedure and absence of contraindications. Patients without INCA were the historical control group. Reported data include demographics, mechanism and severity of injury, number of ribs stabilized, cryoablated nerves, intubation rates and duration of mechanical ventilation. The primary outcome was total morphine milligrams equivalent consumption. Secondary outcomes were intensive care unit length of stay, hospital length of stay, incidence of pneumonia, and tracheostomy rates, and discharge disposition. Long-term outcomes were examined up to 6 months for adverse events.

RESULTS

Sixty-eight patients were included, with 44 receiving INCA. There were no differences in rates of pneumonia (p = 0.106) or duration of mechanical ventilation (p = 0.687), and hospital length of stay was similar between groups (p = 0.059). However, the INCA group demonstrated lower total morphine milligrams equivalent (p = 0.002), shorter intensive care unit length of stay (p = 0.021), higher likelihood of home discharge (p = 0.044), and lower rate of intubation (p = 0.002) and tracheostomy (p = 0.032).

CONCLUSION

Combining INCA with SSRF may further improve in-hospital outcomes for patients with traumatic rib fractures.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Early exclusion leads to cyclical cooperation in repeated group interactions
Authors: Liu Linjie , Xiao Zhilong , Chen Xiaojie , Szolnoki Attila
Published: March 2022

Explaining the emergence and maintenance of cooperation among selfish individuals from an evolutionary perspective remains a grand challenge in biology, economy and social sciences. Social exclusion is believed to be an answer to this conundrum. However, previously related studies often assume one-shot interactions and ignore how free-riding is identified, which seem to be too idealistic. In this work, we consider repeated interactions where excluders need to pay a monitoring cost to identify free-riders for exclusion and free-riders cannot participate in the following possible game interactions once they are identified and excluded by excluders in the repeated interaction process. We reveal that the introduction of such exclusion can prevent the breakdown of cooperation in repeated group interactions. In particular, we demonstrate that an evolutionary oscillation among cooperators, defectors and excluders can appear in infinitely large populations when early exclusion is implemented. In addition, we find that the population spends most of the time in states where cooperators dominate for early exclusion when stochastic mutation–selection is considered in finite populations. Our results highlight that early exclusion is successful in solving the mentioned enigma of cooperation in repeated group interactions.
Modelling glioma progression, mass effect and intracranial pressure in patient anatomy
Authors: Lipková Jana , Menze Bjoern , Wiestler Benedikt , Koumoutsakos Petros , Lowengrub John S.
Published: March 2022

Increased intracranial pressure is the source of most critical symptoms in patients with glioma, and often the main cause of death. Clinical interventions could benefit from non-invasive estimates of the pressure distribution in the patient's parenchyma provided by computational models. However, existing glioma models do not simulate the pressure distribution and they rely on a large number of model parameters, which complicates their calibration from available patient data. Here we present a novel model for glioma growth, pressure distribution and corresponding brain deformation. The distinct feature of our approach is that the pressure is directly derived from tumour dynamics and patient-specific anatomy, providing non-invasive insights into the patient's state. The model predictions allow estimation of critical conditions such as intracranial hypertension, brain midline shift or neurological and cognitive impairments. A diffuse-domain formalism is employed to allow for efficient numerical implementation of the model in the patient-specific brain anatomy. The model is tested on synthetic and clinical cases. To facilitate clinical deployment, a high-performance computing implementation of the model has been publicly released.
Dynamics on higher-order networks: a review
Authors: Majhi Soumen , Perc Matjaž , Ghosh Dibakar
Published: March 2022

Network science has evolved into an indispensable platform for studying complex systems. But recent research has identified limits of classical networks, where links connect pairs of nodes, to comprehensively describe group interactions. Higher-order networks, where a link can connect more than two nodes, have therefore emerged as a new frontier in network science. Since group interactions are common in social, biological and technological systems, higher-order networks have recently led to important new discoveries across many fields of research. Here, we review these works, focusing in particular on the novel aspects of the dynamics that emerges on higher-order networks. We cover a variety of dynamical processes that have thus far been studied, including different synchronization phenomena, contagion processes, the evolution of cooperation and consensus formation. We also outline open challenges and promising directions for future research.
Emergence of lump-like solitonic waves in Heimburg–Jackson biomembranes and nerves fractal model
Authors: El-Nabulsi Rami Ahmad
Published: March 2022

The aim of this study is to extend the soliton propagation model in biomembranes and nerves constructed by Heimburg and Jackson for the case of fractal dimensions. Our analyses are based on the product-like fractal measure concept introduced by Li and Ostoja-Starzewski in their attempt to explore anisotropic fractal elastic media and electromagnetic fields. The mathematical model presented in the paper is formulated for only a part of a single nerve cell (an axon). The analytical and numerical envelop soliton of this equation are reported. The results obtained prove the emergence of lump-type solitonic waves in nerves and biomembranes. In particular, these waves decay algebraically to the background wave in space direction. This scenario is viewed as a particular class of rational localized waves which are solutions of the integrable Ishimori I equation and the (2 + 1) Kadomtsev–Petviashvili I equation. The effects of fractal dimensions are discussed and were found to be significant to some extents.
Smooth stable manifolds for the non-instantaneous impulsive equations with applications to Duffing oscillators
Authors: Lu Weijie , Pinto Manuel , Xia Yonghui
Published: March 2022

In this paper, we present a theory of smooth stable manifold for the non-instantaneous impulsive differential equations on the Banach space or Hilbert space. Assume that the non-instantaneous linear impulsive evolution differential equation admits a uniform exponential dichotomy, we give the conditions of the existence of the global and local stable manifolds. Furthermore,

C

k

-smoothness of the stable manifold is obtained, and the periodicity of the stable manifold is given. Finally, an application to nonlinear Duffing oscillators with non-instantaneous impulsive effects is given, to demonstrate the existence of stable manifold.
Impact of Transition from Conventional Open Radical Cystectomy to Laparoscopic Radical Cystectomy for Neobladder: A Retrospective Study
Authors: Shah Rupesh B , Trivedi Amit D , Rajyaguru Ketan B , Bhatt Parloop A
Published: March 2022

Background

Early operative recovery and good Quality of life are important goals of radical cystectomy. We compare the pre, peri and post operative data between Open radical cystectomy (ORC) and Laparoscopic radical cystectomy (LRC) surgery of neobladder.

Patients and Methods

Retrospective analysis of 13 male consecutive patients who underwent radical cystectomy by a single surgeon was done. Diagnosis of all patients was of invasive bladder cancer. Abdominal and preoperative staging was done using computed tomography. None of them received neoadjuvant chemotherapy. All the patients received same standard template bilateral pelvic lympadenenectomy. The urinary diversion included orthotopic neobladder. All patients were consented prior to study participation.

Results

Of the 13 male patients, six had ORC with neobladder while 7 underwent LRC surgery. Baseline characteristics (age, BMI, comorbidities, tumour grade, lymph node status) were similar in both groups. Incision length was significantly smaller in LRC as compared to ORC group (p <0.0001). Although the operative time was longer in LRC group as compared to ORC it was sufficed by reduced time for analgesics, shorter hospital stay (p<0.05), besides earlier time to liquid intake with immediate removal of nasogastric tube (p<0.001). No major complications were observed in the LRC unlike ORC group where one patient died at 30 days.

Conclusions

Based on the observations of our small study sample peri and postoperative outcomes are promising for LRC compared to ORC for patients undergoing neobladder in terms of the smaller incision length associated with less pain and complications, with speedy recovery without jeopardizing oncological outcomes. Transition of surgeon from ORC to LRC was advantageous to patients.
Viral load dynamics of SARS-CoV-2 Delta and Omicron variants following multiple vaccine doses and previous infection
Authors: Woodbridge Yonatan , Amit Sharon , Huppert Amit , Kopelman Naama M.
Published: March 2022

An important, and often neglected, aspect of vaccine effectiveness is its impact on pathogen transmissibility, harboring major implications for public health policies. As viral load is a prominent factor affecting infectivity, its laboratory surrogate, qRT-PCR cycle threshold (Ct), can be used to investigate the infectivity-related component of vaccine effectiveness. While vaccine waning has previously been observed for viral load, during the Delta wave, it is yet unknown how Omicron viral load is affected by vaccination status, and whether vaccine-derived and natural infection protection are sustainable. By analyzing results of more than 460,000 individuals we show that while recent vaccination reduces Omicron viral load, its effect wanes rapidly. In contrast, a significantly slower waning rate is demonstrated for recovered COVID-19 individuals. Thus, while the vaccine is effective in decreasing morbidity and mortality, their relative minute effect on transmissibility and rapid waning call for reassessment of the scientific justification for “vaccine certificate”, as it may promote false reassurance and promiscuous behavior.
Presumptive Multidrug-Resistant Escherichia coli Isolated in Drinking Water and Soil Sources from Kadamaian, Sabah
Authors: Jamrin Noor Farhani Atiqah , Suhaimi Norshafiqa , Zulkifli Muhammad Zul Izlan , Yusof Nur Athirah
Published: March 2022

Multi-drug-resistant Escherichia coli poses a great threat to human health. E. coli is often used as fecal indicator bacteria to study the sources and fate of fecal contamination in the environment. This study focused on water and soil samples in tourist parks around Kadamaian, Kota Belud from three different villages of Kampung Napungguk, Kampung Pinalabuh and Kampung Tinata. From 23 of tested presumptive E. coli isolates, the percentage of antimicrobial-resistant against a series of antibiotic concentrations ranging from 25, 50, 100 to 500 μg/ml showed resistance towards Chloramphenicol (91.3%), Penicillin (82.6%), Tetracycline (73.9%) and Kanamycin (30.43%). This finding suggested the presence of multi-drug resistance (MDR) of presumptive E. coli from soil samples of Kampung Napungguk and Kampung Tinata. This study alarms the presence of MDR which need further research on identifying the bacterial strains using molecular methods. The findings can then be used to create awareness of potential disease outbreaks in the tourist areas.
Clinical validation and the evaluation of a colorimetric SARS-CoV-2 RT-LAMP assay identify its robustness against RT-PCR
Authors: Erdem M. , Andac-Ozketen A. , Ozketen AC. , Karahan G. , Tozluyurt A. , Palaz F. , Alp A. , Unal S.
Published: March 2022

The novel coronavirus has infected millions of people all around the world and has posed a great risk to global health. Rapid and accurate tests are needed to take early precautions and control the disease. The most routinely used method is real time polymerase chain reaction (RT-PCR) which stands as the gold standard in the detection of SARS-COV-2 viral RNA. However, robust assays as accurate as RT-PCR have been developed for rapid diagnosis and efficient control of the spread of the disease. Reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) is one of the time-saving, accurate and cost-effective alternative methods to RT-PCR. In this study, we study the improved RT-LAMP colorimetric assay (N-Fact) to detect SARS-COV-2 viral RNA within 30 minutes using a primer sets special to N gene. Moreover, RT-LAMP colorimetric assay is subjected to authorized clinical studies to test its ability to detect COVID-19 in its early phases. The results reveal RT-LAMP colorimetric assay is an efficient, robust, and rapid assay to be used as in vitro diagnostic tool display competitiveness compared to RT-PCR.
Accuracy of Rapid Antigen Testing across SARS-CoV-2 Variants
Authors: Drain Paul K. , Bemer Meagan , Morton Jennifer F. , Dalmat Ronit , Abdille Hussein , Thomas Katherine , Uppal Timsy , Hau Derrick , Green Heather R. , Gates-Hollingworth Marcellene A. , AuCoin David P. , Verma Subhash C.
Published: March 2022

Variants of SARS-CoV-2 have mutations in the viral genome that may alter the accuracy of rapid diagnostic tests. We conducted analytical and clinical accuracy studies of two FDA-approved rapid antigen tests—SCoV-2 Ag Detect™ Rapid Test (InBios International, Seattle) and BinaxNOW™ COVID-19 Ag CARD; (Abbott Laboratories, Chicago)—using three using replication-competent variants or strains, including Omicron (B.1.1.529/BA.1), Delta (B.1.617.2), and a wild-type of SARS-CoV-2 (USA-WA1/2020). Overall, we found non-significant differences in the analytical limit of detection or clinical diagnostic accuracy of rapid antigen testing across SARS-CoV-2 variants. This study provides analytical and clinical performance data to demonstrate the preserved accuracy of rapid antigen testing across SARS-CoV-2 variants among symptomatic adults.
Undiagnosed COVID-19 in households with a child with mitochondrial disease
Authors: Gordon-Lipkin Eliza M. , Marcum Christopher , Kruk Shannon , Thompson Elizabeth , Kelly Sophie E.M. , Kalish Heather , Sadtler Kaitlyn , McGuire Peter J.
Published: March 2022

Background

The impact of the COVID-19 pandemic on medically fragile populations, who are at higher risk of severe illness and sequelae, has not been well characterized. Viral infection is a major cause of morbidity in children with mitochondrial disease (MtD), and the COVID-19 pandemic represents an opportunity to study this vulnerable population.

Methods

A convenience sampling cross-sectional serology study was conducted (October 2020 to June 2021) in households (N = 20) containing a child with MtD (N = 22). Samples (N = 83) were collected in the home using a microsampling apparatus and shipped to investigators. Antibodies against SARS-CoV-2 nucleocapsid (IgG), spike protein (IgG, IgM, IgA), and receptor binding domain (IgG, IgM, IgA) were determined by enzyme linked immunosorbent assay.

Results

While only 4.8% of participants were clinically diagnosed for SARS-CoV-2 infection, 75.9% of study participants were seropositive for SARS-CoV-2 antibodies. Most samples were IgM positive for spike or RBD (70%), indicating that infection was recent. This translated to all 20 families showing evidence of infection in at least one household member. For the children with MtD, 91% had antibodies against SARS-CoV-2 and had not experienced any adverse outcomes at the time of assessment. For children with recent infections (IgM+ only), serologic data suggest household members as a source.

Conclusions

COVID-19 was highly prevalent and undiagnosed in households with a child with MtD through the 2020-2021 winter wave of the pandemic. In this first major wave, children with MtD tolerated SARS-CoV-2 infection well, potentially due to household adherence to CDC recommendations for risk mitigation.

Funding

This study was funded by the Intramural Research Program of the National Institutes of Health (HG200381-03).

Clinical trial number

NCT04419870
Altered microRNA expression in severe COVID-19: potential prognostic and pathophysiological role
Authors: Garnier Nathalie , Pollet Kato , Fourcot Marie , Caplan Morgan , Marot Guillemette , Goutay Julien , Labreuche Julien , Soncin Fabrice , Boukherroub Rabah , Hober Didier ,   Lille COVID Research Network (LICORNE), Szunerits Sabine , Poissy Julien , Engelmann Ilka
Published: March 2022

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is ongoing. The pathophysiology of SARS-CoV-2 infection is beginning to be elucidated but the role of microRNAs (miRNAs), small non-coding RNAs that regulate gene expression, remains incompletely understood. They play a role in the pathophysiology of viral infections with potential use as biomarkers. The objective of this study was to identify miRNAs as biomarkers of severe COVID-19 and to analyze their role in the pathophysiology of SARS-CoV-2 infection.

Methods

miRNA expression was measured in nasopharyngeal swabs from 20 patients with severe COVID-19, 21 patients with non-severe COVID-19 and 20 controls. Promising miRNAs to differentiate non-severe from severe COVID-19 patients were identified by differential expression analysis and sparse Partial Least Squares-Discriminant Analysis (sPLS-DA). ROC analysis, target prediction, GO enrichment and pathway analysis were used to analyze the role and the pertinence of these miRNAs in severe COVID-19.

Results

The number of expressed miRNAs was lower in severe COVID-19 patients compared to non-severe COVID-19 patients and controls. Among the differentially expressed miRNAs between severe COVID-19 and controls, 5 miRNAs were also differentially expressed between severe and non-severe COVID-19. sPLS-DA analysis highlighted 8 miRNAs, that allowed to discriminate the severe and non-severe COVID-19 cases. Target and functional analysis revealed enrichment for genes involved in viral infections and the cellular response to infection as well as one miRNA, hsa-miR-15b-5p, that targeted the SARS-CoV-2 RNA.

The comparison of results of differential expression analysis and discriminant analysis revealed three miRNAs, namely hsa-miR-125a-5p, hsa-miR-491-5p and hsa-miR-200b-3p. These discriminated severe from non-severe cases with areas under the curve ranging from 0.76 to 0.80.

Conclusions

Our analysis of miRNA expression in nasopharyngeal swabs revealed several miRNAs of interest to discriminate severe and non-severe COVID-19. These miRNAs represent promising biomarkers and possibly targets for antiviral or anti-inflammatory treatment strategies.
Assessment of a vancomycin dosing guideline and identification of predictive factors associated with dose and drug trough levels
Authors: Gu Qingze , Jones Nicola , Drennan Philip , Peto Tim E.A. , Walker A. Sarah , Eyre David W
Published: March 2022

Background: Guidelines and therapeutic drug monitoring are widely used to optimise vancomycin dosing, but their impact remains unclear.
Objectives: To assess and optimise vancomycin dosing guidelines in a UK teaching hospital group.
Methods: We conducted a retrospective study to evaluate guideline compliance and drug levels following the introduction of a new vancomycin guideline. We used multivariable regression models to investigate factors associated with dosing compliance, drug levels and acute kidney injury (AKI).
Results: 3,767 patients received intravenous vancomycin for ≥24h between 01-January-2016 and 01-June-2021. Compliance with recommended loading and initial maintenance doses increased reached 84% and 70% respectively; 72% of subsequent maintenance doses were correctly adjusted. Only 26% first and 32% subsequent levels reached the target range. Drug levels were independently higher in older patients (1.14mg/L per 10 years older with twice-daily dosing [95%CI 1.03,1.25]), with lower eGFR (0.46 mg/L per 10 mL/min/1.73m2 lower [0.40,0.52]) and higher Elixhauser scores (0.72mg/L per unit higher [0.57,0.88]). For patients with ongoing vancomycin treatment, the conditional probability of achieving target levels at 5 days was >50% and close to 90% at 10 days. Incidence of AKI was low (5.7%), with no evidence that AKI risk increased after guideline implementation (OR=1.09 per year [0.97,1.22], p=0.14). Model estimates were used to propose updated age, weight and eGFR specific guidelines.
Conclusion: Despite good compliance with guidelines for vancomycin dosing, the proportion of drug levels achieving the target range remained suboptimal. Adjusting existing guidelines is required to ensure appropriate dosing and better attainment of therapeutic drug levels.
Sequential appearance and isolation of a SARS-CoV-2 recombinant between two major SARS-CoV-2 variants in a chronically infected immunocompromised patient
Authors: Burel Emilie , Colson Philippe , Lagier Jean-Christophe , Levasseur Anthony , Bedotto Marielle , Lavrard Philippe , Fournier Pierre-Edouard , La Scola Bernard , Raoult Didier
Published: March 2022

Genetic recombination is a major evolutionary mechanism among RNA viruses, and it is common in coronaviruses, including those infecting humans. A few SARS-CoV-2 recombinants have been reported to date whose genome harbored combinations of mutations from different mutants or variants, but a single patient’s sample was analyzed, and the virus was not isolated. Here, we re-port the gradual creation of a hybrid genome of B.1.160 and Alpha variants in a lymphoma patient chronically infected for 14 months, and we isolated the recombinant virus. The hybrid genome was obtained by next-generation sequencing, and recombination sites were confirmed by PCR. This consisted of a parental B.1.160 backbone interspersed with two fragments, including the spike gene, from an Alpha variant. Analysis of seven sequential samples from the patient decoded the recombination steps, including the initial infection with a B.1.160 variant, then a concurrent infec-tion with this variant and an Alpha variant, the generation of hybrid genomes, and eventually the emergence of a predominant recombinant virus isolated at the end of the patient’s follow-up. This case exemplifies the recombination process of SARS-CoV-2 in real life, and it calls for intensifying genomic surveillance in patients coinfected with different SARS-CoV-2 variants, and more gener-ally with several RNA viruses, as this may lead to the creation of new viruses.
Vegetable intake and metabolic risk factors: A Mendelian randomization study
Authors: Feng Qi , Besevic Jelena
Published: March 2022

Background: The associations between vegetable intake and metabolic risk factors remain inconsistent. This study was aimed to investigate the association between cooked and raw vegetable intake with serum lipids, body mass index (BMI), blood pressure and glycemic traits.
Methods: This was a two sample Mendelian randomization study. Nine and 19 genetic variants were identified from genome wide association studies (GWAS) as instrumental variables for cooked and raw vegetable intake. Summary level statistics were used from GWAS of total cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, systolic blood pressure, diastolic blood pressure, BMI, fasting glucose, fasting insulin, glycated haemoglobin and 2 hour glucose after oral glucose tolerance test. Multivariable MR with inverse variance weighted method was performed as primary analysis, while median-based method and MR Egger method were performed as sensitivity analyses.
Results: Vegetable intake was not associated with total cholesterol (-0.06 [-0.30, 0.18] and -0.02 [-0.20, 0.16] for each serving increase of cooked and raw vegetable intake) and triglyceride (-0.12 [-0.36, 0.13] and 0.03 [-0.15, 0.22]). Null evidence was observed for associations between vegetable intake and lipoproteins, blood pressure, BMI, insulin and glycemic measures. Sensitivity analyses generated similar null associations.
Conclusions: We found null association between vegetable intake and metabolic risk factors. This is consistent with previous MR findings of null associations between diet-derived antioxidants and metabolic risk factors.
Socioeconomic status and immune aging in older US Adults in the Health and Retirement Study
Authors: Klopack Eric T. , Thyagarajan Bharat , Faul Jessica D. , Meier Helen C. S. , Ramasubramanian Ramya , Kim Jung Ki , Crimmins Eileen M.
Published: March 2022

Background: Life course socioeconomic and demographic factors including educational attainment, race and ethnicity, and childhood (SES) are very powerful predictors of large inequalities in aging, morbidity, and mortality. Immune aging, including accumulation of late-differentiated, senescent-like lymphocytes and lower level of naive lymphocytes, may play a role in the development of the age-related health inequalities. However, there has been little research investigating association between socioeconomic status and immune aging, particularly age-related changes in lymphocyte percentages.
Methods: This study used nationally representative data from more than 9000 US adults from the Health and Retirement Study to investigate associations between educational attainment, race and ethnicity, and childhood SES and lymphocyte percentages.
Results: Respondents with lower educational attainment, Hispanic adults, and those who had a parent with less than high school education had lymphocyte percentages consistent with more highly accelerated immune aging compared to those with greater educational attainment, non-Hispanic White adults, and respondents who had parents with a high school education, respectively. Associations between education, Hispanic ethnicity, and parents' education and late differentiated senescent-like T lymphocytes (TemRA) and B cells were largely driven by cytomegalovirus (CMV) seropositivity.
Conclusions: Results suggest that CMV is a major driver of observed SES inequalities in immunosenescence and may therefore be an important target for interventions. Naive T lymphocytes may be particularly affected by socioeconomic position and may therefore be of particular interest to research interested in inequalities in health and aging.
Another doubling of excess mortality in the United States relative to its European peers between 2017 and 2021
Authors: Heuveline Patrick
Published: March 2022

A mortality gap between the United States and other high-income nations emerged before the pandemic. International comparisons of Covid-19 mortality suggest this gap might have increased during the pandemic.

Applying average mortality rates of the five largest West European countries to the US population shows that the number of “excess deaths” attributable to this mortality gap continues to increase year after year in the United States. The annual number of such excess deaths has doubled between 2017 and 2021, with most of the increase occurring during the pandemic (+89.1% between 2019 and 2021). In 2021, excess mortality in the United States relative to its European peers contributed 892,491 excess deaths, amounting to 25.8% of all US deaths that year, up from 15.7% in 2017.

Of the 450,224 excess deaths added between 2017 and 2021, 42,317 are attributable to population change (9.4%), 230,672 to differential rates of Covid-19 mortality (51.2%), and the remaining 177,235 to differential rates of mortality from other causes (39.4%, possibly including misclassified deaths due to Covid-19). The contribution of Covid-19 mortality to excess mortality in the United States (relative to its European peers) grew between 2020 and 2021 due to diverging trends in Covid-19 mortality, especially towards the end of 2021 as US vaccination rates plateaued at lower levels than in European countries. While this contribution might be transient, divergent trends in mortality from other causes persistently separates the United States from West European countries. Excess mortality is particularly high between ages 15 and 64. In 2021, nearly half of all US deaths in this age range are excess deaths (48.0%).
Where the truth really lies: Listening to voices from African American communities in the Southern States about COVID-19 vaccine information and communication
Authors: Zhang Ran , Qiao Shan , Mckeever Brooke , Olatosi Bankole , Li Xiaoming
Published: March 2022

Background: High uptake of COVID-19 vaccine is one of the most promising measures to control the pandemic. However, some African American (AA) communities exhibit vaccination hesitancy due to mis- or dis-information. It is important to understand the challenges in accessing reliable COVID-19 vaccine information and to develop feasible health communication interventions based on voices from AA communities.
Methods: We conducted two focus group discussions (FGDs) among 18 community leaders recruited from three counties in South Carolina on October 8 and October 29, 2021. The FGDs were conducted online via Zoom meetings. The FGD data were managed and thematically analyzed using QSR NVivo 12 software.
Results: Participants (73% female and 61% between the ages of 18 and 30) worked primarily in colleges (55.5%), churches (39%), and health agencies (5.5%). We found that challenges of accessing reliable COVID-19 vaccine information in AA communities primarily included structural barriers, information barriers, and lack of trust. Community leaders recommended recruiting trusted messengers, using homecoming events, football games, and other social events to reach target populations and conducting health communication campaigns through open dialogue among stakeholders.
Conclusion: Health communication interventions on COVID-19 vaccine uptake should be grounded in ongoing community engagement, trust-building activities, and transparent communication about vaccine development. Tailoring health communication interventions to different groups may help reduce misinformation spread and thus promote vaccination in AA communities in the Southern States.
Eye drift during fixation predicts visual acuity
Authors: Clark Ashley M. , Intoy Janis , Rucci Michele , Poletti Martina
Published: March 2022

Visual acuity is commonly assumed to be determined by the eye optics and spatial sampling in the retina. Unlike a camera, however, the eyes are never stationary during the acquisition of visual information, a jittery motion known as ocular drift, incessantly displaces stimuli over many photoreceptors. Previous studies have shown that acuity is impaired in the absence of retinal image motion caused by eye drift. However, the relation between individual drift characteristics and acuity remains unknown. Here we show that (a) healthy emmetropes exhibit a large variability in their amount of drift; and (b) that these differences profoundly affect the structure of spatiotemporal signals to the retina. We further show that (c) the spectral distribution of the resulting luminance modulations strongly correlates with individual visual acuity; and (d) that natural inter-trial fluctuations in the amount of drift modulate acuity. As a consequence, in healthy emmetropes acuity can be predicted from the motor behavior elicited by a simple fixation task, without directly measuring it. These results shed new light on how oculomotor behavior contributes to fine spatial vision.

Significance

Healthy humans can visually resolve extremely fine patterns, in some cases with the relevant features spanning less than a single photoreceptor on the retina. This accomplishment is particularly remarkable considering that the eyes are never stationary. Ocular drift—a motion that eludes human awareness—shifts the stimulus across many photoreceptors during the acquisition of visual information. Here we show that visual acuity depends on ocular drift. Natural variations in the amount of drift are associated with acuity both within and across subjects, so that individual acuity limits can be directly inferred from the amount of motion during fixation on a marker. Results closely follow the strength of the luminance modulations caused by ocular drift, providing support to long-standing dynamic theories of visual acuity.