bluuebunny/crossref_metadata_2025 huggingface dataset:
Accelerating Analytics Using Improved Binary Particle Swarm Optimization for Discrete Feature Selection
Authors: Moorthy Rajalakshmi Shenbaga , Pabitha P
Published: June 2021

Feature selection, a combinatorial optimization problem, remains broadly applied in the area of Computational Learning with the aim to construct a model with reduced features so as to improve the performance of the model. Feature selection algorithm aims to identify admissible subgroup of features without sacrificing the accuracy of the model. This research works uses Improved Binary Particle Swarm Optimization (IBPSO) to optimally identify subset of features. The problem of stagnation, trapping in local optima and premature convergence of Binary Particle Swarm Optimization (BPSO) for solving discrete feature selection dispute has been tackled using IBPSO. IBPSO prevents the model from overfitting and also takes less computational time for constructing the model because of reduced feature subset. The sine function, cosine function, position of the random particle and linear decrement of inertial weight are integrated in IBPSO, which balances between exploration and exploitation to identify optimal subset of features. The linear decrement of inertial weight tends to do good level of exploration at the starting phase, whereas at the end it tends to exploit solution space to find the optimal subset of features that are more informative and thereby discarding redundant and irrelevant features. Experimentation is carried out on seven benchmarking datasets obtained from University of California, Irvine repository, which includes various real-world datasets for processing with machine learning algorithms. The proposed IBPSO is compared with conventional metaheuristic algorithms such as BPSO, Simulated Annealing, Ant Colony Optimization, Genetic Algorithm and other hybrid metaheuristic feature selection algorithms. The result proves that IBPSO maximizes the accuracy of the classifier together with maximum dimensionality reduction ratio. Also, statistical tests such as T-test, Wilcoxon signed-pair test are also carried out to demonstrate IBPSO is better than other algorithms taken for experimentation with confidence level of 0.05.
Profile and early outcomes of surgical reconstruction of coronary artery atresia in children
Authors: Li Hanmei , Wang Hailing , Lin Ye , Rui Lu , Li Shoujun
Published: June 2021

OBJECTIVES

Coronary artery atresia is a rare coronary artery anomaly in children and has a high rate of misdiagnosis. We aimed to summarize the profile and early outcomes after the surgical reconstruction of coronary artery atresia in children.

METHODS

A retrospective analysis was performed in 12 consecutive patients with coronary artery atresia who were admitted to the Department of Paediatric Cardiac Surgery of Fuwai Hospital between October 2016 and September 2020. Ten patients underwent surgical reconstruction of the coronary artery with the pulmonary artery anterior wall, and 8 patients underwent concomitant mitral valvuloplasty.

RESULTS

There were 6 females and 6 males, with an age of 1.75 years [interquartile range (IQR), 1.0–3.5] and weight of 10.0 kg (IQR, 8.9–14.75). There were 10 cases of left coronary artery atresia and 2 cases of right coronary artery atresia. All the patients were initially misdiagnosed in the outpatient clinic, but further nonselective coronary angiography confirmed the diagnosis of coronary artery atresia. In all 10 patients with mitral regurgitation, echocardiogram of the mitral valve chordae and papillary muscle revealed ischaemic changes. The clamp time was 89.0 min (IQR, 75.0–101.0), the pump time was 126.0 min (IQR, 119.0–132.0) and the intensive care unit stay time was 1.5 days (IQR, 1.0–3.0). No perioperative deaths were noted. After 9.5 months (IQR, 5.5–13.5) of follow-up, 2 patients with fractional shortening that significantly decreased to 14.1% and 14.8% died and 1 patient had moderate pericardial effusion that improved after treatment with oral diuretics. Coronary artery ultrasound and enhanced computed tomography showed a patent main coronary artery in all the patients.

CONCLUSIONS

Coronary artery atresia in children is often associated with mitral regurgitation, and mitral valve chordae and papillary muscle exhibit ischaemic changes. Coronary artery reconstruction is safe and effective in children with coronary artery atresia.
Greyzone myocardial fibrosis and ventricular arrhythmias in patients with a left ventricular ejection fraction >35%
Authors: Zegard Abbasin , Okafor Osita , de Bono Joseph , Kalla Manish , Lencioni Mauro , Marshall Howard , Hudsmith Lucy , Qiu Tian , Steeds Richard , Stegemann Berthold , Leyva Francisco
Published: June 2021

Aims

To determine whether myocardial fibrosis and greyzone fibrosis (GZF) on cardiovascular magnetic resonance (CMR) is associated with ventricular arrhythmias in patients with coronary artery disease (CAD) and a left ventricular ejection fraction (LVEF) >35%.

Methods and results

In this retrospective study of CAD patients, GZF mass using the 3SD method (GZF3SD) and total fibrosis mass using the 2SD method (TF2SD) on CMR were assessed in relation to the primary, combined endpoint of sudden cardiac death, ventricular tachycardia, ventricular fibrillation, or resuscitated cardiac arrest. Among 701 patients [age: 65.8 ± 12.3 years (mean ± SD)], 28 (3.99%) patients met the primary endpoint over 5.91 years (median; interquartile range 4.42–7.64). In competing risks analysis, a GZF3SD mass ≥5.0 g was strongly associated with the primary endpoint [subdistribution hazard ratio (sHR): 17.4 (95% confidence interval, CI 6.64–45.5); area under receiver operator characteristic curve (AUC): 0.85, P < 0.001]. A weaker association was observed for TF2SD mass ≥23 g [sHR 10.4 (95% CI 4.22–25.8); AUC: 0.80, P < 0.001]. The range of sHRs for GZF3SD mass (1–527) was wider than for TF2SD mass (1–37.6).

Conclusions

In CAD patients with an LVEF >35%, GZF3SD mass was strongly associated with the arrhythmic endpoint. These findings hold promise for its use in identifying patients with CAD and an LVEF >35% at risk of arrhythmic events.
Gene targeting using pre-assembled Cas9 ribonucleoprotein and split-marker recombination in Pleurotus ostreatus
Authors: Boontawon Tatpong , Nakazawa Takehito , Xu Haibo , Kawauchi Moriyuki , Sakamoto Masahiro , Honda Yoichi
Published: June 2021

Until recently, classical breeding has been used to generate improved commercial mushroom strains; however, classical breeding remains to be laborious and time-consuming. In this study, we performed gene mutagenesis using Cas9 ribonucleoprotein (Cas9 RNP) as a plasmid-free genome editing in Pleurotus ostreatus, which is one of the most economically important cultivated mushrooms. The pre-assembled Cas9/sgRNA targeting pyrG was introduced into protoplasts of a wild-type monokaryotic P. ostreatus strain PC9, which resulted in a generation of strains exhibiting resistance to 5-fluoroorotic acid. Small insertions/deletions at the target site were identified using genomic PCR followed by sequencing. The results showed Cas9 RNP-assisted gene mutagenesis could be applied for the molecular breeding in P. ostreatus and in other edible mushroom strains. Furthermore, gene disruption via split-marker recombination using the Cas9 RNP system was also successfully demonstrated in wild-type P. ostreatus PC9. This method could overcome the disadvantages of NHEJ-deficiency in conventional studies with gene targeting, and also difficulty in gene targeting in various non-model agaricomycetes.
The ecological impact of a bacterial weapon: microbial interactions and the Type VI secretion system
Authors: Gallegos-Monterrosa Ramses , Coulthurst Sarah J
Published: June 2021

Bacteria inhabit all known ecological niches and establish interactions with organisms from all kingdoms of life. These interactions are mediated by a wide variety of mechanisms and very often involve the secretion of diverse molecules from the bacterial cells. The Type VI secretion system (T6SS) is a bacterial protein secretion system that uses a bacteriophage-like machinery to secrete a diverse array of effectors, usually translocating them directly into neighbouring cells. These effectors display toxic activity in the recipient cell, making the T6SS an effective weapon during inter-bacterial competition and interactions with eukaryotic cells. Over the last two decades, microbiology research has experienced a shift towards using systems-based approaches to study the interactions between diverse organisms and their communities in an ecological context. Here, we focus on this aspect of the T6SS. We consider how our perspective of the T6SS has developed and examine what is currently known about the impact that bacteria deploying the T6SS can have in diverse environments, including niches associated with plants, insects and mammals. We consider how T6SS-mediated interactions can affect host organisms by shaping their microbiota, as well as the diverse interactions that can be established between different microorganisms through the deployment of this versatile secretion system.
Galectin-3 plays a protective role in Leishmania (Leishmania) amazonensis infection
Authors: Oliveira Rafael M , Teixeira Thaise L , Rodrigues Cassiano C , da Silva Aline A , Borges Bruna C , Brígido Rebecca T S , Teixeira Samuel C , Dos Santos Marlus A , Servato João Paulo S , de O Santos Débora , Silva Marcelo J B , Goulart Luiz R , da Silva Claudio V
Published: June 2021

Leishmania (L.) amazonensis is one of the species responsible for the development of cutaneous leishmaniasis in South America. After entering the vertebrate host, L. (L.) amazonensis invades mainly neutrophils, macrophages and dendritic cells. Studies have shown that gal-3 acts as a pattern recognition receptor. However, the role of this protein in the context of L. (L.) amazonensis infection remains unclear. Here, we investigated the impact of gal-3 expression on experimental infection by L. (L.) amazonensis. Our data showed that gal-3 plays a role in controlling parasite invasion, replication and the formation of endocytic vesicles. Moreover, mice with gal-3 deficiency showed an exacerbated inflammatory response. Taken together, our data shed light to a critical role of gal-3 in the host response to infection by L. (L.) amazonensis.
Tame Algebras Have Dense g-Vector Fans
Authors: Plamondon Pierre-Guy , Yurikusa Toshiya , Keller Bernhard
Published: June 2021

The $\textbf{g}$-vector fan of a finite-dimensional algebra is a fan whose rays are the $\textbf{g}$-vectors of its two-term presilting objects. We prove that the $\textbf{g}$-vector fan of a tame algebra is dense. We then apply this result to obtain a near classification of quivers for which the closure of the cluster $\textbf{g}$-vector fan is dense or is a half-space, using the additive categorification of cluster algebras by means of Jacobian algebras. As another application, we prove that for quivers with potentials arising from once-punctured closed surfaces, the stability and cluster scattering diagrams only differ by wall-crossing functions on the walls contained in a separating hyperplane. The appendix is devoted to the construction of truncated twist functors and their adjoints.
Schur Function at General Points and Limit Shape of Perfect Matchings on Contracting Square Hexagon Lattices with Piecewise Boundary Conditions
Authors: Li Zhongyang
Published: June 2021

We obtain a new formula to relate the value of a Schur polynomial with variables $(x_1,\ldots ,x_N)$ with values of Schur polynomials at $(1,\ldots ,1)$. This allows one to study the limit shape of perfect matchings on a square hexagon lattice with periodic weights and piecewise boundary conditions. In particular, when the edge weights satisfy certain conditions, asymptotics of the Schur function imply that the liquid region of the model in the scaling limit has multiple connected components, while the frozen boundary consists of disjoint cloud curves.
AnL4 Maximal Estimate for Quadratic Weyl Sums
Authors: Barron Alex
Published: June 2021

We show that $ \bigg \|\sup _{0 < t < 1} \big |\sum _{n=1}^{N} e^{2\pi i (n(\cdot ) + n^2 t)}\big | \bigg \|_{L^{4}([0,1])} \leq C_{\epsilon } N^{3/4 + \epsilon } $ and discuss some applications to the theory of large values of Weyl sums. This estimate is sharp for quadratic Weyl sums, up to the loss of $N^{\epsilon }$.
Finite Dimensionality in the Non-commutative Choquet Boundary: Peaking Phenomena and C*-Liminality
Authors: Clouâtre Raphaël , Thompson Ian
Published: June 2021

We explore the finite-dimensional part of the non-commutative Choquet boundary of an operator algebra. In other words, we seek finite-dimensional boundary representations. Such representations may fail to exist even when the underlying operator algebra is finite dimensional. Nevertheless, we exhibit mechanisms that detect when a given finite-dimensional representation lies in the Choquet boundary. Broadly speaking, our approach is topological and requires identifying isolated points in the spectrum of the $\textrm{C}^{\ast }$-envelope. This is accomplished by analyzing peaking representations and peaking projections, both of which being non-commutative versions of the classical notion of a peak point for a function algebra. We also connect this question with the residual finite dimensionality of the $\textrm{C}^{\ast }$-envelope and to a stronger property that we call $\textrm{C}^{\ast }$-liminality. Recent developments in matrix convexity allow us to identify a pivotal intermediate property, whereby every matrix state is locally finite dimensional.
Comparison of Oral Fluid and Urine for Detection of Fentanyl Use Using Liquid Chromatography with Tandem Mass Spectrometry
Authors: Mahowald Grace K , Khaliq Tahira P , Griggs David , O Mi , Flood James G , Uljon Sacha
Published: June 2021

Background

We compared oral fluid (OF) and urine (UR) for detection of fentanyl (FEN) use in addiction medicine-psychiatry (AMP) clinics.

Methods

We measured FEN and norfentanyl (NRFEN) in UR with a limit of detection (LOD) of 2.0 µg/L and FEN in OF with an LOD of 0.5 µg/L by LC–MS/MS in 311 paired samples and compared the 2 matrices when higher OF and UR LODs were used.

Results

Urine (UR) detected more FEN use than OF using a LOD of 2.0 µg/L and 0.5 µg/L, respectively. FEN and/or NRFEN were detected in 44 and 59 UR specimens, respectively, and FEN in 46 OF specimens (43 OF+UR+, 3 OF+UR−, 16 OF−UR+, and 249 OF−UR−). In UR there were no instances with FEN positive and NORFEN negative. UR creatinine was <20 mg/dL in the 3 OF+UR− specimen pairs. The median OF/UR analyte concentration ratios in positive sample pairs were 0.23 for OF FEN/UR FEN and 0.02 for OF FEN/UR NRFEN.

Conclusions

We demonstrate that UR detects more FEN use than OF in an AMP setting when UR FEN and UR NORFEN LODs of 2.0 µg/L are used. OF is less sensitive than UR in detecting FEN use, but is still valuable for cases with low UR creatinine and/or suspected adulteration or substitution of UR. The UR vs OF comparison statistics are greatly impacted by even minimal adjustments of the LOD.
Addressing intraarticular pathology at the time of anteverting periacetabular osteotomy for acetabular retroversion is associated with better short-term patient-reported outcomes
Authors: Panos Joseph A , Gutierrez Claudia N , Wyles Cody C , Bingham Joshua S , Mara Kristin C , Trousdale Robert T , Sierra Rafael J
Published: June 2021

Periacetabular osteotomy (PAO) is effective in the management of developmental dysplasia of the hip and femoroacetabular impingement secondary to acetabular retroversion. During anteverting PAO for acetabular retroversion, the need for both labral treatment and femoral head–neck junction osteochondroplasty remains equivocal. Accordingly, this study evaluated patient-reported outcome measures (PROM) and reoperation rates after anteverting PAO with or without intraarticular intervention. Cases of anteverting PAO performed at a single institution between November 2009 and January 2016 were retrospectively reviewed. Patients were divided into three groups: no intervention and intraarticular intervention with arthrotomy or arthroscopy. Subsequently, patients were reclassified by the intraarticular procedure performed at surgery into major (labral repair, femoral head–neck osteochondroplasty) and minor (labral debridement, femoral/acetabular chondroplasty) groups. The cohort was 75% female, median age was 19.5 years and mean body mass index was 25.0 kg/m2. Preoperative to postoperative improvement was compared to minimal clinically important differences (MCID) for eight PROM. Patients receiving major interventions exceeded MCID in a greater proportion of PROM compared to minor and no intervention groups (P < 0.007); major or minor interventions did not increase the risk of reoperation over no intervention (P ≥ 0.39). Based on the current data, surgeons performing anteverting PAO for acetabular retroversion should perform arthroscopic or open labral repair and assess for impingement after the correction and perform a head–neck junction osteochondroplasty if indicated.
Acute ischaemia of the upper limb following peripherally inserted central catheter—a venous to arterial complication cascade
Authors: Hamdulay Khaleel A , van den Bosch Rene
Published: June 2021

Peripherally inserted central catheters (PICC) are useful access devices that allow for longer-term intravenous access. This allows patients requiring an extended period of intravenous medication to have this administered without the need for repeat vascular punctures. Even minimally invasive procedures such as line insertion come with risks. Of particular interest to this article is a limb threatening complication soon after line placement. We discuss the PICC line catheter tip as the likely cause for arrhythmia that lead to an embolic occlusion of an upper limb and required acute surgical intervention for limb salvage. We stress the rapid sequence of events that lead to this ultimate complication. We also stress the importance for all clinicians to be aware of these risks and take a cautious approach as the majority of patients requiring longer-term access are already at greater risks of thromboembolic disease due to their comorbidities.
De Garengeot hernia masquerading as a painless groin lump: a case report
Authors: Chaudhry Muhammad A , Neduchelyn Yuwaraja , Ivanovski Ivan , Sarwar Hassan
Published: June 2021

De Garengeot’s hernia is a rare subtype of femoral hernia in which the appendix is located within the herniated sac. These cases are important to report as both the diagnosis and treatment are quite challenging. We present a case of a 68-year-old gentleman with few months history of a lump in the right groin that gave him mild discomfort but no other symptoms. Initial investigations with an ultrasound did not prove to be helpful and so a plan was made to surgically explore the lump. The appendiceal tip was incarcerated within the hernial sac. The appendix was removed using an open inguinal incision with repair of the defect using a light weight partially absorbable mesh. It is important to consider the possibility of a De Garangeot’s Hernia as a differential diagnosis for patients presenting with a groin lump.
Shaping the root system: the interplay between miRNA regulatory hubs and phytohormones
Authors: Barrera-Rojas Carlos Hernán , Otoni Wagner Campos , Nogueira Fabio Tebaldi Silveira
Published: June 2021

The root system commonly lies underground, where it provides anchorage for the aerial organs, as well as nutrients and water. Both endogenous and environmental cues contribute to the establishment of the root system. Among the endogenous cues, microRNAs (miRNAs), transcription factors, and phytohormones modulate root architecture. miRNAs belong to a subset of endogenous hairpin-derived small RNAs that post-transcriptionally control target gene expression, mostly transcription factors, comprising the miRNA regulatory hubs. Phytohormones are signaling molecules involved in most developmental processes. Some miRNAs and targets participate in more than one hormonal pathway, thereby providing new bridges in plant hormonal crosstalk. Unraveling the intricate network of molecular mechanisms underlying the establishment of root systems is a central aspect in the development of novel strategies for plant breeding to increase yield and optimize agricultural land use. In this review, we summarize recent findings describing the molecular mechanisms associated with the interplay between miRNA regulatory hubs and phytohormones to ensure the establishment of a proper root system. We focus on post-embryonic growth and development of primary, lateral, and adventitious roots. In addition, we discuss novel insights for future research on the interaction between miRNAs and phytohormones in root architecture.
A study of the central stellar populations of galaxies in SDSS-IV MaNGA: identification of a subsample with unusually young and massive stars
Authors: Kauffmann Guinevere
Published: June 2021

This paper describes a search for galaxy centres with clear indications of unusual stellar populations with an initial mass function flatter than Salpeter at high stellar masses. Out of a sample of 668 face-on galaxies with stellar masses in the range $10^{10}\!-\!10^{11} \, \mathrm{M}_{\odot }$, I identify 15 galaxies with young- to intermediate-age central stellar populations with unusual stellar population gradients in the inner regions of the galaxy. In these galaxies, the 4000-Å break is either flat or rising towards the centre of the galaxy, indicating that the central regions host evolved stars, but the H α equivalent width also rises steeply in the central regions. The ionization parameter [O iii]/[O ii] is typically low in these Galactic Centres, indicating that ionizing sources are stellar rather than AGN. Wolf–Rayet features characteristic of hot young stars are often found in the spectra and these also get progressively stronger at smaller galactocentric radii. These outliers are compared to a control sample of galaxies of similar mass with young inner stellar populations, but where the gradients in H α equivalent width and 4000-Å break follow each other more closely. The outliers exhibit central Wolf–Rayet red bump excesses much more frequently, they have higher central stellar and ionized gas metallicities, and they are also more frequently detected at 20-cm radio wavelengths. I highlight one outlier where the ionized gas is clearly being strongly perturbed and blown out either by massive stars after they explode as supernovae, or by energy injection from matter falling on to a black hole.
Beyond city expansion: multi-scale environmental impacts of urban megaregion formation in China
Authors: Zhou Weiqi , Yu Wenjuan , Qian Yuguo , Han Lijian , Pickett Steward T A , Wang Jing , Li Weifeng , Ouyang Zhiyun
Published: June 2021

Environmental degradation caused by rapid urbanization is a pressing global issue. However, little is known about how urban changes operate and affect environments across multiple scales. Focusing on China, we found urbanization was indeed massive from 2000 to 2015, but it was also very uneven, exhibiting high internal city dynamics. Urban areas in China as a whole became less green, warmer, and had exacerbated PM2.5 pollution. However, environmental impacts differed in newly developed versus older areas of cities. Adverse impacts were prominent in newly urbanized areas, while old urban areas generally showed improved environmental quality. In addition, regional environmental issues are emerging as cities expand, connect and interact to form urban megaregions. To turn urbanization into an opportunity for, rather than an obstacle to, sustainable development, we must move beyond documenting urban expansion to understand the environmental consequences of both internal city dynamics and the formation of urban megaregions.
Metabolomics analysis of poly(l-lactic acid) nanofibers' performance on PC12 cell differentiation
Authors: Su Xiaoman , Huang Yan , Chen Rong , Zhang Yiwen , He Meichen , Lü Xiaoying
Published: June 2021

The aim of this article is to reveal the influence of aligned/random poly(l-lactic acid) (PLLA) nanofibers on PC12 cell differentiation from the perspective of metabolic level. First, three materials—PLLA aligned nanofibers (PLLA AF), PLLA random nanofibers (PLLA RF) and PLLA films (control)—were prepared by electrospinning and spin coating. Their surface morphologies were characterized. Subsequently, the cell viability, cell morphology and neurite length of PC12 cells on the surface of the three materials were evaluated, indicating more neurites in the PLLA RF groups but the longer average neurite length in the PLLA AF groups. Next, the metabolite profiles of PC12 cells cultured on the surface of the three nanofibers after 12 h, 24 h and 36 h showed that, compared with the control, 51, 48 and 31 types of differential metabolites were detected at the three time points among the AF groups, respectively; and 56, 45 and 41 types among the RF groups, respectively. Furthermore, the bioinformatics analysis of differential metabolites identified two pathways and three metabolites critical to PC12 cell differentiation influenced by the nanofibers. In addition, the verification experiment on critical metabolites and metabolic pathways were performed. The integrative analysis combining cytology, metabolomics and bioinformatics approaches revealed that though both PLLA AF and RF were capable of stimulating the synthesis of neurotransmitters, the PLLA AF were more beneficial for PC12 cell differentiation, whereas the PLLA RF were less effective.
Real-life efficacy of guselkumab in patients with early psoriatic arthritis
Authors: Pantano Ilenia , Mauro Daniele , Romano Francesca , Gambardella Alessio , Valenti Mario , Simone Davide , Iacono Daniela , Costanzo Antonio , Argenziano Giuseppe , Ciccia Francesco
Published: June 2021

Objectives

To assess the efficacy of the novel anti-IL-23 monoclonal antibody guselkumab in a real-life observational cohort of patients with early PsA.

Methods

We conducted an observational study on patients with early PsA followed by the joint dermatology-rheumatology clinics of two Italian centres starting therapy with guselkumab for severe skin involvement. Each patient was evaluated at baseline and every 24 weeks for one year, recording Disease Activity Index for PsA (DAPSA), PASI, VAS Pain, VAS Prutitus, Patient's Global Assessment (PtGA) and assessing DAPSA response.

Results

Twenty-four patients were recruited (16 women). The mean duration of skin disease was 12.5 years (CI 8; 17), but all patients had a shorter articular disease duration, 21.29 months (CI 15.9; 26.68). At baseline, all patients displayed a moderate cutaneous disease with a mean PASI of 15.2 (CI 11.7–18.6) and high disease activity, characterized by mean DAPSA of 26.84 (CI 22.49–31.19). An inflammatory low back pain was reported by five patients (20%) with a mean BASDAI 5.1 (CI 4,38–5,85) at baseline. The majority of guselkumab-treated patients (n = 18; 75%) reached DAPSA remission or DAPSA low disease activity after six months. Seventeen out of 24 patients completed 12 months of treatment, 11 of them (65%) in low disease activity, six (35%) in remission. All patients with axial disease reported improvement of inflammatory low back pain at week 24 with a mean BASDAI 2.98 (CI 2,18– 3,77). No significant side effects were reported.

Conclusions

Real-life data on a cohort of early PsA patients confirm the efficacy and safety of guselkumab on peripheral and axial manifestations.
Red Blood Cell Stiffness Driving Patient Symptoms: A Study of Red Blood Cell Population Rigidity in Sickle Cell Patient Genotype SC Relation to Overlooked Clinical Symptoms
Authors: Shamoun Mark , Gutierrez Mario , Eniola-Adefeso Omolola
Published: June 2021

Sickle cell disease (SCD) is a systemic hematological disease. Various genotypes of the disease exist; however, the two most common include hemoglobin SS (Hgb SS) and hemoglobin SC (Hgb SC) disease. Hgb SC is typically considered a less severe genotype; however, some patients with SC disease still have significant complications. Ektacytometry is utilized to measure red blood cell deformability in sickle cell patients and may help identify patients at risk for severe disease. We described a patient with genotype hemoglobin SC with a more severe phenotype, who we show to have very rigid red blood cells via ektacytometry.
De novo FZR1 loss-of-function variants cause developmental and epileptic encephalopathies including Myoclonic Atonic Epilepsy
Authors: Manivannan Sathiya N. , Roovers Jolien , Smal Noor , Myers Candace T. , Turkdogan Dilsad , Roelens Filip , Kanca Oguz , Chung Hyung-Lok , Scholz Tasja , Hermann Katharina , Bierhals Tatjana , Caglayan S. Hande , Stamberger Hannah , Mefford Heather , de Jonghe Peter , Yamamoto Shinya , Weckhuysen Sarah , Bellen Hugo J.
Published: June 2021

FZR1, which encodes the Cdh1 subunit of the Anaphase Promoting Complex, plays an important role in neurodevelopment by regulating cell cycle and by its multiple post-mitotic functions in neurons. In this study, evaluation of 250 unrelated patients with developmental epileptic encephalopathies (DEE) and a connection on GeneMatcher led to the identification of three de novo missense variants in FZR1. Two variants led to the same amino acid change. All individuals had a DEE with childhood onset generalized epilepsy, intellectual disability, mild ataxia and normal head circumference. Two individuals were diagnosed with the DEE subtype Myoclonic Atonic Epilepsy (MAE). We provide gene burden testing using two independent statistical tests to support FZR1 association with DEE. Further, we provide functional evidence that the missense variants are loss-of-function (LOF) alleles using Drosophila neurodevelopment assays. Using three fly mutant alleles of the Drosophila homolog fzr and overexpression studies, we show that patient variants do not support proper neurodevelopment. With the recent report of a patient with neonatal-onset DEE with microcephaly who also carries a de novo FZR1 missense variant, our study consolidates the relationship between FZR1 and DEE, and expands the associated phenotype. We conclude that heterozygous LOF of FZR1 leads to DEE associated with a spectrum of neonatal to childhood onset seizure types, developmental delay and mild ataxia. Microcephaly can be present but is not an essential feature of FZR1-encephalopathy. In summary, our approach of targeted sequencing using novel gene candidates and functional testing in Drosophila will help solve undiagnosed MAE/DEE cases.
Prevalence evolution of SARS-CoV-2 infection in the Municipality of São Paulo, 2020 - 2021
Authors: Albuquerque Jose O M , Kamioka Gabriela A , Madalosso Geraldine , Costa Selma A , Ferreira Paula B , Pino Francisco A , Sato Ana Paula S , Carvalho Ana Carolina A , Amorim Ana Beatriz P , Aires Caroline C , Kataoka Ana Paula A G , Savani Elisa S M M , Bessa Thirsa A F , Aguiar Breno S , Failla Marcelo A , Santos Edson A , Brito Edjane M T , Santos Maria C H , Silva Solange M S , Caldeira Luiz A V , Zamarco Luiz C , Fonseca Sandra M S , Lima Marcia M C , Marques Ivanilda A , Silva Fabiana E V , Glasser Paula R , Burihan Patrícia C P R , Cavazzana Cinthya L , Lara Renata C , Mello Debora S , Pellini Alessandra C G , Nishio Fernando Y , Kian Fernanda M , Braga Elza S , Bertelli Nilza M P , Fracini Wagner , Gonçalves Marcelo D A , Zular Paulete S , Piva Regiane S , de Masi Eduardo
Published: June 2021

Objectives

To estimate the evolution of the prevalence of SARS-CoV-2 virus infection among residents aged 18 years or over in the municipality of São Paulo.

Methods

This is a population-based household survey conducted every 15 days, between June and September 2020 and January and February 2021. In total, 11 phases were performed. The presence of antibodies against SARS-CoV-2 was identified in venous blood using a lateral flow test, Wondfo Biotech. In the last phase, it was combined with an immunoenzymatic test, Euroimmun. Participants also answered a semi-structured questionnaire on sociodemographic and economic factors and social distancing measures. Prevalence estimates and 95% confidence intervals were estimated according to the region, Human Development Index, sex, age group, ethnicity, education, income and variables associated with risk or prevention of the infection. To compare the frequencies among the categories of each variable, the chi-square test with Rao Scott correction was used, considering a 5% significance level.

Results

In total, 23,397 individuals were interviewed and had their samples collected. The estimated prevalence of antibodies against SARS-CoV-2 ranged from 9.7% (95%CI: 7.9-11.8%) to 25.0% (95%CI: 21.7-28.7). The prevalence of individuals with antibodies against SARS-CoV-2 was higher among black and pardo people, people with lower schooling, people with lower income and among residents of regions with lower Human Development Index. The lowest prevalences were associated with recommended measures of disease protection. The proportion of asymptomatic infection was 45.1%.

Conclusion

The estimated prevalence of SARS-CoV-2 infection was lower than the cumulative incidence variation, except for the last phase of the study. The differences in prevalence estimates observed among subpopulations showed the social inequality as a risk of infection. The lower prevalence observed among those who could follow prevention measures reinforce the need to maintain the social distancing measures as ways to prevent SARS-CoV-2 infection.
A Short Plus Long-Amplicon Based Sequencing Approach Improves Genomic Coverage and Variant Detection In the SARS-CoV-2 Genome
Authors: Arana Carlos , Liang Chaoying , Brock Matthew , Zhang Bo , Zhou Jinchun , Chen Li , Cantarel Brandi , SoRelle Jeffrey , Hooper Lora V. , Raj Prithvi
Published: June 2021

High viral transmission in the COVID-19 pandemic has enabled SARS-CoV-2 to acquire new mutations that impact genome sequencing methods. The ARTIC.v3 primer pool that amplifies short amplicons in a multiplex-PCR reaction is one of the most widely used methods for sequencing the SARS-CoV-2 genome. We observed that some genomic intervals are poorly captured with ARTIC primers. To improve the genomic coverage and variant detection across these intervals, we designed long amplicon primers and evaluated the performance of a short (ARTIC) plus long amplicon (MRL) sequencing approach. Sequencing assays were optimized on VR-1986D-ATCC RNA followed by sequencing of nasopharyngeal swab specimens from five COVID-19 positive patients. ARTIC data covered >90% of the virus genome fraction in the positive control and four of the five patient samples. Variant analysis in the ARTIC data detected 67 mutations, including 66 single nucleotide variants (SNVs) and one deletion in ORF10. Of 66 SNVs, five were present in the spike gene, including nt22093 (M177I), nt23042 (S494P), nt23403 (D614G), nt23604 (P681H), and nt23709 (T716I). The D614G mutation is a common variant that has been shown to alter the fitness of SARS-CoV-2. Two spike protein mutations, P681H and T716I, which are represented in the B.1.1.7 lineage of SARS-CoV-2, were also detected in one patient. Long-amplicon data detected 58 variants, of which 70% were concordant with ARTIC data. Combined analysis of ARTIC +MRL data revealed 22 mutations that were either ambiguous (17) or not called at all (5) in ARTIC data due to poor sequencing coverage. For example, a common mutation in the ORF3a gene at nt25907 (G172V) was missed by the ARTIC assay. Hybrid data analysis improved sequencing coverage overall and identified 59 high confidence mutations for phylogenetic analysis. Thus, we show that while the short amplicon (ARTIC) assay provides good genomic coverage with high throughput, complementation of poorly captured intervals with long amplicon data can significantly improve SARS-CoV-2 genomic coverage and variant detection.
Awareness and Agreement with Neurofibromatosis Care Guidelines among Neurofibromatosis Specialists
Authors: Merker Vanessa L. , Knight Pamela , Radtke Heather B. , Yohay Kaleb , Ullrich Nicole J. , Plotkin Scott R. , Jordan Justin T.
Published: June 2021

Introduction

Given the wide range of neurofibromatoses (NF) symptoms and medical specialties involved in NF care, we sought to evaluate the level of awareness of, and agreement with, published NF clinical guidelines among United States NF specialists.

Methods

An anonymous, cross-sectional online survey was distributed to attendees of a large NF research conference. Respondents self-reported demographics, practice characteristics, awareness of seven NF guideline publications, and level of agreement with up to 40 individual guidelines using a 5-point Likert scale. We calculated the proportion of guidelines that each clinician rated “strongly agree”, and assessed for differences in guideline awareness and agreement by respondent characteristics.

Results

Sixty-three clinicians (49% female; 80% academic practice) across >8 medical specialties completed the survey. Awareness of each guideline publication ranged from 53%-79% of respondents; specialists had higher awareness of publications endorsed by their medical professional organization (p<0.05). The proportion of respondents who “strongly agree” with individual guidelines ranged from 17%-83%; for 16 guidelines, less than 50% of respondents “strongly agree”. There were no significant differences in overall agreement with guidelines based on clinicians’ gender, race, specialty, years in practice, practice type (academic/private practice/other), practice location (urban/suburban/rural), or involvement in NF research (p>0.05 for all).

Conclusions

We identified wide variability in both awareness of, and agreement with, published NF care guidelines among NF experts. Future efforts should focus on evidence-based, consensus-driven methods to update and disseminate guidelines across this multi-specialty group. Patients and caregivers should also be consulted to anticipate barriers to accessing and implementing guideline-driven care.
Rapid spread of the SARS-CoV-2 δ variant in French regions in June 2021
Authors: Alizon Samuel , Haim-Boukobza Stéphanie , Foulongne Vincent , Verdurme Laura , Trombert-Paolantoni Sabine , Lecorche Emmanuel , Roquebert Bénédicte , Sofonea Mircea T.
Published: June 2021

Analysing 9,030 variant-specific tests performed on SARS-CoV-2 positive samples collected in France between 31 May and 21 June 2021 reveals a rapid growth of the δ variant in 3 French regions. The next weeks will prove decisive but the magnitude of the estimated transmission advantages could represent a major challenge for public health authorities.
FAMILY’S RESILIENCE IN CAREGIVING ELDERLY WITH DEMENTIA: A SYSTEMATIC REVIEW
Authors: Pradana Anung Ahadi , Rohayati
Published: June 2021

Objective

Dementia patients have complex needs that may become a burden to those who caregive them. They are treated at home by family members due to financial limitations and lack of support from health services. Therefore, the measurement of self-resilience in caregivers needs special attention from professionals.

Method

This study used a systematic review method from 4 databases consisting of the CINAHL, ProQuest, PubMed, and Google Scholar between 2015 till 2020; 17 articles were considered to meet the inclusion criteria.

Results

Caregiver of elderly with dementia has a tendency to experience burdens that affect the quality of the care performed. The level of resilience that caregivers have can help reduce the level of burden they experience and improve their quality of life.

Conclusions

Social support and formal support by health workers for caregivers have a significantly positive effect in increasing the level of resilience of caregivers.
Evidence for a serotonergic subtype of major depressive disorder: A NeuroPharm-1 study
Authors: Köhler-Forsberg Kristin , Ozenne Brice , Landman Elizabeth B. , Larsen Søren V. , Poulsen Asbjørn S. , Dam Vibeke H. , Ip Cheng-Teng , Jørgensen Anders , Meyer Michal , Eiberg Hans R. L. , Svarer Claus , Jørgensen Martin B. , Frokjaer Vibe G. , Knudsen Gitte M.
Published: June 2021

Selective serotonin reuptake inhibitors (SSRIs) are the first line pharmacological treatment of Major Depressive Disorder (MDD), but only about half of patients benefit from it. Cerebral serotonin 4 receptor (5-HT4R) binding measured with positron emission tomography (PET) is inversely related to serotonin levels and can serve as a proxy for brain serotonin levels. We here determine if 5-HT4R differs between healthy and MDD individuals and if it is associated with successful outcomes of serotonergic treatment of MDD. We [11C]-SB207145 PET-scanned 100 (71 F) untreated patients with moderate to severe MDD and 91 (55 F) healthy controls; 40 patients were re-scanned after 8 weeks treatment. All patients started treatment with the SSRI escitalopram and were followed clinically after 1, 2, 4, 8 and 12 weeks. Treatment response was measured as change from baseline.

Before treatment, patients with MDD had 8% lower global 5-HT4R binding than controls (95%CI[-13.1%;-2.5%], p<0.001). Non-responders did not differ from controls, whereas remitters had 9% lower binding than controls ([-16.1%;-2.7%], p=0.004). Independent of treatment outcomes, patients reduced their neostriatal 5-HT4R binding (−9%, [-12.8%;-5.0%], p<0.001) after serotonergic intervention.

Overall, patients with MDD have lower cerebral 5-HT4R binding than controls, suggesting that 5-HT4R is a biomarker for MDD. The observation that SSRI treatment leads to reduced neostriatal 5-HT4R binding supports that the treatment does indeed increase brain 5-HT levels. Patients who remit to SSRIs have lower cerebral 5-HT4R prior to treatment than controls whereas non-responders do not differ. We propose that non-responders to SSRI’s constitute a subgroup with non-serotonergic depression.

ClinicalTrials.gov Identifier: NCT02869035

Registry name: Treatment Outcome in Major Depressive Disorder

URL: https://clinicaltrials.gov/ct2/show/NCT02869035?term=NCT02869035&draw=2&rank=1
WHotLAMP: A simple, inexpensive, and sensitive molecular test for the detection of SARS-CoV-2 in saliva
Authors: Ng David , Pinharanda Ana , Vogt Merly C. , Litwin-Kumar Ashok , Stearns Kyle , Thopte Urvashi , Cannavo Enrico , Enikolopov Armen , Fiederling Felix , Kosmidis Stylianos , Noro Barbara , Rodrigues-Vaz Ines , Shayya Hani , Andolfatto Peter , Peterka Darcy S. , Tabachnik Tanya , D’Armiento Jeanine , Goldklang Monica , Bendesky Andres
Published: June 2021

Despite the development of effective vaccines against SARS-CoV-2, epidemiological control of the virus is still challenging due to slow vaccine rollouts, incomplete vaccine protection to current and emerging variants, and unwillingness to get vaccinated. Therefore, frequent testing of individuals to identify early SARS-CoV-2 infections, contact-tracing and isolation strategies remain crucial to mitigate viral spread. Here, we describe WHotLAMP, a rapid molecular test to detect SARS-CoV-2 in saliva. WHotLAMP is simple to use, highly sensitive (3.6 viral RNA copies per microliter of saliva) and specific, as well as inexpensive, making it ideal for frequent screening. Moreover, WHotLAMP does not require toxic chemicals or specialized equipment and thus can be performed in point-of-care settings, and may also be adapted for resource-limited environments or home use. While applied here to SARS-CoV-2, WHotLAMP can be modified to detect other pathogens, making it adaptable for other diagnostic assays, including for use in future outbreaks.
Seroprevalence of COVID-19 in HIV Population
Authors: Naik Shivdas Rajaram , Kumar Swasthi S , Mittal Ankit , Swain Satish , Ranjan Sanjay , Soneja Manish , Sinha Sanjeev , Nischal Neeraj , Jorwal Pankaj , Chaturvedi Pradeep , Wig Naveet
Published: June 2021

Background

Seroprevalence helps us to estimate the exact prevalence of a disease in a population. Although the world has been battling this pandemic for more than a year now, we still do not know about the burden of this disease in people living with HIV/AIDS (PLHA). Seroprevalence data in this population subset is scarce in most parts of the world, including India. The current study aimed to estimate the seroprevalence of anti-SARS-CoV-2 IgG antibody among PLHA.

Aim

To determine the seroprevalence of SARS-CoV-2 antibodies in PLHA.

Method

This was a cross-sectional study conducted at a tertiary care hospital in North India. We recruited HIV positive patients following at the ART centre of the institute. Anti-SARS-CoV-2 IgG antibody levels targeting recombinant spike receptor-binding domain (RBD) protein of SARS CoV-2 were estimated in serum sample by the chemiluminescent immunoassay method.

Results

A total of 164 patients were recruited in the study with a mean age (±SD) of 41.2 (±15.4) years, of which 55% were male. Positive serology against SARS CoV-2 was detected in 14% patients (95% CI: 9.1-20.3%).

Conclusion

The seroprevalence of COVID-19 infection in PLHA was lower than the general population in the same region, which ranged from 23.48% to 28.3% around the study period.
Knowledge and use of lactational amenorrhea as a family planning method among adolescent mothers in Uganda: a secondary analysis of Demographic and Health Surveys between 2006 and 2016
Authors: Birabwa Catherine , Bakkabulindi Pamela , Wafula Solomon T , Waiswa Peter , Benova Lenka
Published: June 2021

Objective

To assess the level of knowledge and use of lactational amenorrhea method (LAM) among adolescents in Uganda between 2006 and 2016 using nationally representative data from Demographic and Health Surveys (DHS).

Design

Cross-sectional design involving analysis of three DHS (2006, 2011, and 2016) in Uganda.

Setting

The data was collected in Uganda. The DHS are nationally representative surveys on a wide range of indicators including contraception knowledge and use.

Participants

A total of 8,250 adolescents (15-19 years) and 7,110 young women (20-24 years) were included.

Primary outcome measure

Use of LAM among adolescents and young women with a livebirth within six months before each survey.

Results

In 2016, less than 1% of eligible adolescents correctly used LAM and 56% were passively benefitting from LAM. The median duration of postpartum amenorrhea (PPA) among adolescents in 2016 was 6.9 months, declining from 8.3 months in 2006. Compared to adolescents, eligible young women had higher knowledge of LAM and higher medianPPA duration in 2016. The percentage of eligible adolescents who met the LAM criteria irrespective of whether they reported LAM use (protected by LAM) decreased from 76% in 2006 to 57% in 2016. More than 50% of eligible adolescents were aware of LAM in 2016, increasing from 6% in 2006, potentially in part due to change in survey question.

Conclusion

Despite increasing awareness of LAM, reported and correct use of LAM was low among adolescents who could benefit from this method in Uganda, and declining over time. Support for adolescents to harness the benefits of correct LAM use should be increased. Additional research is needed to better understand the dynamics of LAM use in adolescents, including the transition to use of other modern contraceptive methods.

Strengths and limitations of this study

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Lactational amenorrhea method has the potential to promote healthy timing and spacing of pregnancies and to reduce repeat adolescent births, yet, its use among Ugandan adolescents has not been examined.

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This study provides useful insights into the behavior of adolescents mothers which can be targeted to improve their reproductive knowledge and wellbeing.

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The study used data from three standardised nationally representative surveys, thus findings are generalizable and comparable over time and across age groups.

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Assessment of knowledge of LAM was affected by a change in the phrasing of the question in 2016, thus providing limited comparability with previous surveys.

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The measurement of LAM use was based on self-report.