bluuebunny/crossref_metadata_2025 huggingface dataset:
Number of Autonomous Cognitive Agents in a Neural Network
Authors: Kak Subhash
Published: March 2022

This paper considers several aspects of the relationship between size, structure, speed of propagation and the number of autonomous cognitive agents in a neural network. While memory and function generation capacities of neural networks with scale-invariant structure have been investigated extensively, the number of autonomous agents, associated with the simultaneous processing of the independent components of the data, has not received prior attention. We propose the emergence of the dichotomy of causal and noncausal regions created by the speed of propagation, in which the autonomous cognitive agents are not bound in a causal relationship with other agents. Arguments are presented for why the count of autonomous agents is best estimated with respect to the dimensionality of the underlying space. The number of autonomous agents obtained for the human brain equals 25, and it is significant that the number in the sub-system modules also turns out to be close to the same value. This number equals the number of enumerative categories of reality in at least one philosophical tradition, and this coincidence may be attributed to the capacity of consciousness to reflect on its own structure. It is possible that near equality across layers provides a special uniqueness to the human brain. We propose that the findings of this study will be useful in the design of neural-network-based AI systems that are designed to emulate human cognitive capacity.
Blockage of the Monoamine Oxidase by a Natural Compound to Overcome Parkinson’s Disease via Computational Biology
Authors: Sherafatizangeneh Mahsa , Farshadfar Chiako , Mojahed Nooshin , Noorbakhsh Akbar , Ardalan Noeman
Published: March 2022

The dopamine (DA) metabolism changes are significant in Parkinson’s disease (PD). Levels of monoamine oxidases (MAOs) play a critical role in DA metabolism and oxidative damage. Increased levels of the MAO-B enzyme in the elderly raise oxidative damage and enhance neurodegenerative processes. Inhibiting MAO-B as an attractive target would be the best method for treating and understanding Parkinson’s disease. This study aimed to recognize a suitable inhibitor for the MAO-B enzyme using computational biology and compared it with Safinamide as a positive control. We used various computational biology techniques such as binding free energy, virtual screening, molecular dynamics (MD), and docking considerations to achieve the goal. To obtain a potent inhibitor, 41,852 compounds were taken from the Zinc database. After preparing compounds and the MAO-B enzyme, screening was performed using AutoDock Vina software. After screening, a potent natural inhibitor (ZINC00261335) was picked, and then, subsequent MD simulations for both ZINC00261335 and Safinamide were conducted via GROMACS software. The stability of the MAO-B_ZINC00261335 complex was excellent during the simulation, and the results of MM-PBSA analysis explicated that ZINC00261335 with ([Formula: see text]118.353[Formula: see text]kJ[Formula: see text]mol[Formula: see text]) is more potent than Safinamide ([Formula: see text]89.305[Formula: see text]kJ[Formula: see text]mol[Formula: see text]). Ultimately, the ADME study (lipophilicity, drug similarity and pharmacokinetic parameters) for ZINC00261335 was revealed, which is acceptable for human use. This study indicates that ZINC00261335 is a suitable MAO-B inhibitor and a great candidate for more laboratory studies.
Anti-Myxovirus Resistance Protein-1 Immunoglobulin A Autoantibody in Idiopathic Pulmonary Fibrosis
Authors: Arai Toru , Hirose Masaki , Hamano Yoshimasa , Kagawa Tomoko , Murakami Akihiro , Kida Hiroshi , Kumanogoh Atsushi , Inoue Yoshikazu
Published: March 2022

Background. We have previously analysed serum autoantibody levels in patients with idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (iNSIP), and healthy controls and identified the autoantibody against anti-myxovirus resistance protein-1 (MX1) to be a specific autoantibody in iNSIP. We found that a higher anti-MX1 autoantibody level was a significant predictor of a good prognosis in patients with non-IPF idiopathic interstitial pneumonias. In this retrospective study, we sought to clarify the prognostic significance of the anti-MX1 autoantibody in IPF. Methods. We measured anti-MX1 immunoglobulin (Ig) G, IgA, and IgM autoantibody levels by enzyme-linked immunosorbent assay in serum collected at the time of diagnosis from 71 patients with IPF diagnosed according to the 2018 IPF guideline. The gender-age-physiology (GAP) index was calculated in each case. Results. The study population (59 men and 12 women) had a median age of 67 years. Serum anti-MX1 IgG and IgA autoantibody levels correlated positively with GAP stage (

p
<
0.05

). Univariate Cox proportional hazards regression analysis did not identify an elevated anti-MX1 IgG, IgA, or IgM autoantibody level as a significant prognostic factor; however, a higher anti-MX1 IgA autoantibody level heralded significantly poorer survival after adjustment for GAP stage (

p
=
0.030

) and for percent forced vital capacity and modified Medical Research Council score (

p
=
0.018

). Neither the anti-MX1 IgG autoantibody nor the IgM autoantibody could predict survival after these adjustments. Conclusions. The serum anti-MX1 IgA autoantibody level is a significant prognostic factor in IPF. Further studies are needed to clarify the pathophysiological role of this autoantibody in IPF.
Bullous Scabies in an Immunocompromised Host
Authors: Wester James R. , Jackson Lesley E , Mokgosi Kathryn , Barak Tomer , Hazeem Mahmoud Abu
Published: March 2022

A 40-year-old woman with a history of poorly controlled HIV presented to a district referral hospital in rural Botswana for a generalized skin rash of several months duration. The highly pruritic rash predominantly involved her hands and feet and was associated with bullae that were present for days at a time before rupturing without drainage or discharge. The patient endorsed night sweats, periodic fevers, occasional cough productive of blood-tinged sputum, fatigue, and weight loss. On admission, CD4 count was 46 cells/mm3 and viral load was >750000 copies/mL. Pulmonary tuberculosis testing via sputum was negative twice. A blood count demonstrated eosinophilia. Oral acyclovir was started empirically for disseminated herpes virus infection, with topical beclomethasone and intravenous antibiotics for possible superinfected bullous dermatosis. With inadequate response to treatment, a skin biopsy was obtained and microscopic examination demonstrated scabies mites. The absence of skin burrows, the presence of bullae, and working in a low-resource setting without direct access to microscopic examination delayed diagnosis. The patient was initiated on topical permethrin. Oral ivermectin was not available in country and was obtained from overseas shipment, delaying treatment initiation. Drastic improvement was seen after the patient initiated ivermectin. A local nurse in the patient’s village visited her community and found multiple individuals with active scabies infection. The patient’s discharge was delayed until these community members were treated successfully with topical permethrin. This case describes an atypical presentation of scabies in an under-resourced setting, demonstrating unique diagnostic, therapeutic, and public health challenges.
Using a Divergence Regularization Method to Solve an Ill-Posed Cauchy Problem for the Helmholtz Equation
Authors: Barnes Benedict , Aidoo Anthony Y. , Ackora-Prah Joseph
Published: March 2022

The ill-posed Helmholtz equation with inhomogeneous boundary deflection in a Hilbert space is regularized using the divergence regularization method (DRM). The DRM includes a positive integer scaler that homogenizes the inhomogeneous boundary deflection in the Helmholtz equation’s Cauchy issue. This guarantees the existence and uniqueness of the equation’s solution. To reestablish the stability of the regularized Helmholtz equation and regularized Cauchy boundary conditions, the DRM uses its regularization term

1
+

α

2
m

e

m

, where

α
>
0

is the regularization parameter. As a result, DRM restores all three Hadamard requirements for well-posedness.
Botanical from the Fruits Mesocarp of Raphia vinifera Displays Antiproliferative Activity and Is Harmless as Evidenced by Toxicological Assessments
Authors: Nguenang Gaëlle S. , Mbaveng Armelle T. , Bonsou Idrios N. , Chi Godloves F. , Kuete Victor
Published: March 2022

Raphia vinifera is widely used to treat several diseases including digestive disorders, dysentery, and genitourinary infections. In this study, the mineral contents, the cytotoxicity, and the toxicological effect of the crude CHCl3/MeOH extract (RVM) from the mesocarp of Raphia vinifera were evaluated. The mineral contents were evaluated using the method described by the Association of Official Analytical Chemists (AOAC). The cytotoxicity of both extract and chemical compounds from the plants was determined by a resazurin reduction assay (RRA). The toxicological studies were carried out using the experimental procedure of the Organization for Economic Cooperation and Development (OECD). After killing the rats, biochemical, histopathological, and hematological studies were performed. The result indicated that RVM is rich in zinc (6.52 mg/100 g of DM) and sodium (194.5 mg/100 g of DM). RVM had a cytotoxicity effect with IC50 values lower than 30 μg/mL in 18/18 cancer cell lines tested. These recorded IC50 values were between 12.35 µg/mL (toward CCRF-CEM leukemia cells) and 26.66 µg/mL (toward SKMel-505 BRAF wild-type melanoma cells). Raphvinin 4 displayed good cytotoxicity against MaMel-80aBRAF-V600E homozygous mutant with the IC50 of 10.42 μM. RVM was relatively nontoxic to rats, the median lethal dose (DL50) being above 5000 mg/kg body weight. However, during the oral administration period extending for 28 days, precautions should be taken due to the increase in urinary creatinine level and decrease in spleen weight in the male rats given the highest dose (1000 mg/kg) of extract. Conclusively, the extract of Raphia vinifera is weakly toxic in rats and could be further used in the development of anticancer phytomedicines.
Postmastectomy Reconstruction in Male Breast Cancer
Authors: Deldar Romina , Sayyed Adaah A. , Towfighi Parhom , Aminpour Nathan , Sogunro Olutayo , Son Jennifer D. , Fan Kenneth L. , Song David H.
Published: March 2022

Introduction. Less than 1% of all breast cancers are diagnosed in males. In females, postmastectomy breast reconstruction is associated with increased patient satisfaction. However, there is a paucity of literature describing reconstructive options for postmastectomy deformity in the male chest. The purpose of this systematic review was to evaluate postmastectomy reconstruction outcomes in males with breast cancer. Methods. A systematic review was performed in accordance with PRISMA guidelines. Ovid MEDLINE, Embase, Cochrane, and Web of Science were queried for records pertaining to the study question using medical subject heading (MeSH) terms such as “male breast cancer,” “mastectomy,” and “reconstruction.” No limitations were placed on the year of publication, country of origin, or study size. Study characteristics and patient demographics were collected. Primary outcomes of interest included postoperative complications, recurrence rate, and mortality rate. Results. A total of 11 articles examining 29 male patients with breast cancer who underwent postmastectomy reconstruction were included for analysis. Literature was most commonly available in the form of case reports. The average age was 59.6 +/−11.4 years. Reconstruction methods included fat grafting (n = 1, 3.4%), silicone implants (n = 1, 3.4%), and autologous chest wall reconstruction with local flaps (n = 26, 89.7%). Postoperative complications occurred in two patients (6.8%), including partial nipple necrosis (n = 1) and hypertrophic scarring (n = 1). Of the studies reporting patient satisfaction, all patients were pleased with the aesthetic appearance of their chest. Conclusion. This systematic review revealed the limited availability of research regarding postmastectomy chest reconstruction in males with breast cancer. Nevertheless, the evidence available suggests that reconstruction can restore a patient’s body image and, thus, should be regularly considered and discussed with male patients. Larger studies are warranted to further shed light on this population.
Probabilistic Double Hierarchy Linguistic TOPSIS Method for MAGDM and Its Application to Teaching Quality Evaluation of College English
Authors: Wang Fengling
Published: March 2022

College English is a compulsory course for college students. The teaching level of teachers in this course has naturally been evaluated by various schools. The teaching quality evaluation of college English is frequently viewed as a multiple attribute group decision‐making (MAGDM) issue. The probabilistic double hierarchy linguistic not only conforms to people’s language expression habit of “adverb + adjective,” but can also accurately express its importance. Therefore, this paper comes up with the PDHL‐TOPSIS mean for MAGDM based on the PDHLTS environment and applies it to the teaching quality evaluation of college English. On the one hand, we bring information entropy into the determination of target weight. The PDHL‐TOPSIS technique is constructed and utilized for teaching level evaluation. Eventually, the PDHL‐TOPSIS technique is compared with other decision‐making means, and the novel mean turns out to be significant and valid.
Expressive Arts Therapy Combined with Progressive Muscle Relaxation following Music for Perioperative Patients with Gynecological Malignancies: A Pilot Study
Authors: Liu Xing , Ren Jian-Hua , Jiang Sha-Sha , Tan Yan , Ma Se-Ge , Huang Yan
Published: March 2022

Objective. We aimed to assess the impact of an expressive arts therapy combined with progressive muscle relaxation following music on mental health (anxiety and hope) in patients with gynecological malignancies undergoing surgery. Methods. This was a nonrandomized controlled trial. Eligible patients had a primary or recurrent gynecological malignancy scheduled to be treated with surgery. The intervention consisted of three sessions (preoperation, postoperation, and predischarge) during the perioperative period. Firstly, before starting the first session of intervention, all patients completed three questionnaires including a Hospital Anxiety and Depression Scale (HADS), a Herth Hope Index (HHI), and a State Anxiety Inventory (SAI), and the intervention group patients also had to complete the SAI questionnaire again after completing the intervention. Secondly, after the second session of intervention, all patients completed the SAI questionnaire, with the intervention group completed the SAI questionnaire before the intervention. Thirdly, after the third session of intervention, all patients completed HHI and SAI questionnaires, with the intervention group completed the SAI questionnaire before the intervention. Also, to subjectively rate the benefit of expressive arts therapy, the intervention group additionally completed a separate, supplemental questionnaire. Results. A total of 116 patients were enrolled and 110 included in the final analysis. No group differences were found for HHI scores between the intervention and control participants (Cohen’s d = 0.19,

P
=
0.31

), although there was a substantial improvement in intervention participants’ HHI scores compared to the standard care control participants. There was a statistically significant improvement in intervention participants’ SAI from preintervention to postintervention of preoperation (Cohen’s d = −0.23,

P
=
0.002

) and postoperation (Cohen’s d = −0.34,

P
≤
0.001

). However, no differences were observed for the predischarge period (Cohen’s d = −0.09,

P
=
0.118

). Besides, a supplemental questionnaire indicated that 52 (98%) patients felt that expressive arts therapy was beneficial. Conclusions. Expressive art therapy combined with progressive muscle relaxation under music may be of some effect on alleviating perioperative anxiety in patients with gynecologic malignancies. Therefore, further relevant studies with large samples and multicenters are urgently needed to provide a reliable evidence-based basis for perioperative psychological care of patients with gynecologic malignancies and to promote rapid recovery of patients. It is recommended that further art therapy studies to examine the impact of patient-tailored arts therapy interventions on spiritual well-being in patients with gynecological malignancies, especially in the perioperative period.
Design of Multichannel Resource Adaptive Scheduling Algorithm for English Online Translation Teaching
Authors: Zhang Mei
Published: March 2022

In order to optimize the multichannel resource scheduling of English online translation teaching and realize the goal of adaptive scheduling algorithm, a multichannel resource adaptive scheduling algorithm for English online translation teaching is designed. The clustering algorithm is used to sort out various English online translation teaching multichannel resources and remove redundancy. Build a unified standard specification; establish an English online translation teaching resource scheduling model with three modules of foundation layer, environment layer, and application layer; form an easy-to-find data set; build an adaptive scheduling algorithm function module of system management, standard management, media materials, online courses, courseware library, and test question library; and optimize the integration speed under multiobjective scheduling algorithm; this paper analyzes the multichannel resource scheduling process of English online translation teaching and realizes the research on the designed adaptive scheduling algorithm. The experimental results show that the test results of each functional module of the scheduling platform under the designed algorithm meet the functional requirements, and the update amount of resources is close to the update upper limit, which can reasonably manage teaching resources and improve students’ interest and learning ability.
The Use of Opioids and Pain Medications in the Management of Postoperative Pain in Total Knee Arthroplasty Patients: A Retrospective Study
Authors: Almustafa Ammar , Der-Boghossian Asdghig , Sheikh Taha Abdel Majid
Published: March 2022

Purpose. The opioid crisis amplified the concern for the appropriate use of opioids. Our study aims to investigate the pain levels and amount of opiates needed during the first three days following total knee arthroplasty (TKA), whereby Drug Enforcement Administration (DEA) Schedule II oral opiates are not available. Methods. A year-long retrospective review of adult patients who underwent TKA was conducted. The postoperative pain scores and mean morphine equivalents (MME) were measured. These outcomes were assessed according to demographics, anesthesia, and analgesia used. Results. For our 78 patients, there was no statistical difference for stratification by baseline characteristics except in spinal anesthesia, which decreased pain on the first day. Conversely, MME increased to its significantly highest of 14.22 ± 29.58 mg on day 3. The effect was noted for patient-controlled analgesia where patients with intravenous analgesia received less opioid than those on epidural analgesia on postoperative day one. Conclusions. Using a similar regimen of analgesia, postoperative pain following TKA would be controlled by a relatively low amount of opioids by the third postoperative day. Spinal anesthesia and patient-controlled epidural analgesia were linked to better pain control and less opioid needed.
The Prediction of Sports Economic Development Prospect in Different Regions by Improved Artificial Bee Colony Algorithm
Authors: Liu Lei , Song Guangda
Published: March 2022

In order to study the development of the sports economy in different regions and analyze the future development prospect of sports economy, this paper uses the k‐clustering method to improve the artificial bee colony algorithm and further improve the clustering degree of the bee colony. Among them, the improved artificial bee colony algorithm reduces the incidence of local extreme and improves the accuracy of calculation by setting the weight and threshold of indicators. MATLAB simulation results show that the prediction accuracy of the improved artificial bee colony algorithm for the development prospect of sports economy is 96–99%, and the calculation time is 0–17 seconds. Therefore, the improved artificial bee colony algorithm can best predict the development of the sports economy in different regions, and its accuracy, periodicity, and calculation time are better than those of the original artificial bee colony algorithm.
Quality of Life, Depression, and Anxiety in Patients Undergoing Renal Replacement Therapies in Saudi Arabia
Authors: Shdaifat Emad Adel
Published: March 2022

Despite improvements in renal replacement therapy (RRT) for end-stage renal disease (ESRD), it continues to have serious negative impacts on quality of life (QOL) and emotional status. This study determines the association between demographic characteristics and the negative emotional states of depression, anxiety, and stress in Saudi Arabia. A comparative cross-sectional study was conducted in the Eastern Region of Saudi Arabia. Convenience sampling was used to recruit participants comprising hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (Tx) patients. They completed the Short Form-36 Survey and the Depression, Anxiety, Stress Scale (DASS). The physical component summary (PCS) score was similar for HD (41.7) and PD (41.5), but higher among Tx (45.2). The mental component summary (MCS) score was similar between HD (48.0) and Tx (48.8), but lower in PD (42.3). The majority of patients in all groups had normal levels of depression, anxiety, and stress. Overall, the study found that PCS was higher among Tx patients compared to HD and PD, while MCS was higher among HD and Tx patients than PD patients. Most patients’ levels of depression, anxiety, and stress were within the normal range. Those findings will provide policymakers and health managers with the significant factors which can affect the QOL of dialysis and Tx patients.
Experimental Study on Axial Compression Performance of 7A04 High Strength Aluminum Alloy Circular Tube Concrete Short Column
Authors: Zhang Zuo-Jin , Han Feng-Xia , Liu Qing
Published: March 2022

The application of tube-filled concrete composite columns is becoming more and more popular. The traditional tube-filled column is easy to rust and expensive to maintain, which leads to the practical need of replacing high-strength aluminum alloy. 7A04 aluminum alloy has high strength and strong corrosion resistance, which is more in line with the material requirements of modern building structures. In view of this, four groups of 7A04 aluminum alloy tube concrete short columns were tested under axial compression, and the corresponding ABAQUS finite element simulation was established. The influence of tube thickness and concrete strength grade on compressive strength, ductility, transverse deformation coefficient, and improvement coefficient of strong concrete strength of composite column is considered in this paper. The results show that the failure mode of composite short columns is central uplift or shear failure. The tube thickness of high-strength aluminum tube has a great influence on the strength of specimens, and the ductility of composite columns decreases with the decrease of the collar coefficient. The finite element model can well reflect the development trend of the load-strain curve, and the formula of composite column bearing capacity proposed by regression analysis can well predict the strength of 7A04 aluminum alloy tubular concrete short column. The research results have a certain reference significance for the structural design of high strength aluminum concrete-filled columns.
Supply Gap of Urban and Rural Public Goods Based on Big Data Mining Technology
Authors: Lin Yanqiu
Published: March 2022

The issue of the supply gap of public goods (PG) between urban and rural (UR) areas is a subject of great socio-economic significance and practical research value. To a large extent, it is related to the smooth progress of my country’s socialist market economy. The gap between the supply and demand of UR PG can be well analyzed by applying data mining (DM) technology in the era of big data. Due to the unbalanced supply of UR PG, this paper studies the distribution gap of UR PG through DM. This article mainly uses experimental, comparative, and survey methods to compare and analyze the urban-rural income gap and uses modern technology to describe the relationship between the supply of PG and income. Experimental results show that the UR income gap ratio is above 2, and the gap is still large. Therefore, for the supply of PG, there are also certain differences between UR areas.
Effects of Horizontal Resolution, Domain Size, Boundary Conditions, and Surface Heterogeneity on Coarse LES of a Convective Boundary Layer
Authors: Ovchinnikov Mikhail , Fast Jerome D. , Berg Larry K. , Gustafson William I. , Chen Jingyi , Sakaguchi Koichi , Xiao Heng
Published: March 2022

Atmospheric properties in a convective boundary layer vary over a wide range of spatial scales and are commonly studied using large-eddy simulations (LES) in various configurations. We examine how the boundary layer depth and distribution of variability across scales are affected by LES grid spacing, domain size, inhomogeneity of surface properties, and external forcing. Two different setups of the Weather Research and Forecasting (WRF) model are analyzed. A semi-idealized configuration uses a periodic domain, flat surface, prescribed homogeneous surface heat fluxes, and horizontally uniform profiles of large-scale advective tendencies. A nested LES setup employs a larger domain and realistic initial and boundary conditions, including an interactive land surface model with representative topography and vegetation and soil types. Subdomains of identical size are analyzed for all simulations. Characteristic structure sizes are quantified using the variability scales L50 and L95, defined such that features smaller than that contain 50% and 95% of the total variance, respectively. Progressive increase in L50 from vertical velocity to temperature and moisture structures is systematically reproduced in all simulation configurations. This dependence of L50 on the considered variable complicates the development of scale-aware parameterizations for models with grid spacing in the “terra incognita”. In simulations using a larger domain with heterogeneous surface properties, the development of internal mesoscale patterns significantly affects variance distributions inside analyzed subdomains. Sizes of boundary layer structures also strongly depend on the LES grid spacing and, in case of heterogeneous surface and topography, on location of the subdomain inside a larger computational domain.
Distribution of Article Citation Frequency, Citation Skew, and Impact Factor in Otolaryngology Journals
Authors: Sedaghat Ahmad R.
Published: March 2022

The objectives of this study were to determine the degree of citation skew in otolaryngology journals and how article citation distribution affects their impact factors (IFs). Forty‐one “otorhinolaryngology” journals in the Clarivate Journal Citation Reports database were identified and their article citation data from 2017 to 2020 extracted. Article citation frequency was remarkably similar across most journals, consistent with the narrow distribution of IFs (mean [SD], 1.9 [0.9]). Although the percentage of a journal’s articles cited more than its IF during the IF citation window (mean [SD] of 32.4% [7.9%] of journals’ articles)—reflecting citation skew—was not correlated with IF, the percentage of a journal’s articles that were cited at least once (mean [SD] of 62.5% [15.3%] of articles) was highly correlated (ρ = 0.92, P < .001) with its IF. Although citation skew exists, otolaryngology journals’ overall portfolios of published works—not a small number of highly cited articles causing citation skew—likely predominate their IFs.
Pegcetacoplan for paroxysmal nocturnal hemoglobinuria
Authors: Gerber Gloria F. , Brodsky Robert A.
Published: March 2022

Approximately a third of patients with paroxysmal nocturnal hemoglobinuria (PNH) remain transfusion dependent or have symptomatic anemia despite treatment with a C5 inhibitor. Pegcetacoplan inhibits complement proximally at the level of C3 and is highly effective in treating persistent anemia resulting from C3-mediated extravascular hemolysis. We describe the rationale for C3 inhibition in the treatment of PNH and discuss preclinical and clinical studies using pegcetacoplan and other compstatin derivatives. We propose an approach for sequencing complement inhibitors in PNH.
Bradykinin-induced angioedema in the emergency department
Authors: Hébert Jacques , Boursiquot Jean-Nicolas , Chapdelaine Hugo , Laramée Benoit , Desjardins Marylin , Gagnon Rémi , Payette Nancy , Lepeshkina Oleksandra , Vincent Matthieu
Published: March 2022

Background

Acute airway angioedema commonly occurs through two distinct mechanisms: histamine- and bradykinin-dependent. Although they respond to distinct treatments, these two potentially life-threatening states present similarly. Poor recognition of the bradykinin-dependent pathway leads to treatment errors in the emergency department (ED), despite the availability of multiple pharmacologic options for hereditary angioedema (HAE) and other forms of bradykinin-induced angioedema. Here, we consider the pathophysiology and clinical features of bradykinin-induced angioedema, and we present a systematic literature review exploring the effectiveness of the available therapies for managing such cases.

Methods

PubMed searches using ‘emergency’, ‘bradykinin’ and various therapeutic product names identified studies reporting the efficacy of treatments for bradykinin-induced angioedema in the ED setting. In all, 22 studies met prespecified criteria and are analysed here.

Findings

Whereas histamine-induced angioedema has a faster onset and often presents with urticaria, bradykinin-induced angioedema is slower in onset, with greater incidence of abdominal symptoms. Acute airway angioedema in the ED should initially be treated with anaphylactic protocols, focusing on airway management and treatment with epinephrine, antihistamine and systemic steroids. Bradykinin-induced angioedema should be considered if this standard treatment is not effective, despite proper dosing and regard of beta-adrenergic blockade. Therapeutics currently approved for HAE appear as promising options for this and other forms of bradykinin-induced angioedema encountered in the ED.

Conclusion

Diagnostic algorithms of bradykinin-induced angioedema should be followed in the ED, with early use of approved therapies to improve patient outcomes.
Comparative analysis of the kinomes of Plasmodium falciparum, Plasmodium vivax and their host Homo sapiens
Authors: Adderley Jack , Doerig Christian
Published: March 2022

Background

Novel antimalarials should be effective across all species of malaria parasites that infect humans, especially the two species that bear the most impact, Plasmodium falciparum and Plasmodium vivax. Protein kinases encoded by pathogens, as well as host kinases required for survival of intracellular pathogens, carry considerable potential as targets for antimalarial intervention (Adderley et al. Trends Parasitol 37:508–524, 2021;  Wei et al. Cell Rep Med 2:100423, 2021). To date, no comprehensive P. vivax kinome assembly has been conducted; and the P. falciparum kinome, first assembled in 2004, requires an update. The present study, aimed to fill these gaps, utilises a recently published structurally-validated multiple sequence alignment (MSA) of the human kinome (Modi et al. Sci Rep 9:19790, 2019). This MSA is used as a scaffold to assist the alignment of all protein kinase sequences from P. falciparum and P. vivax, and (where possible) their assignment to specific kinase groups/families.

Results

We were able to assign six P. falciparum previously classified as OPK or ‘orphans’ (i.e. with no clear phylogenetic relation to any of the established ePK groups) to one of the aforementioned ePK groups. Direct phylogenetic comparison established that despite an overall high level of similarity between the P. falciparum and P. vivax kinomes, which will help in selecting targets for intervention, there are differences that may underlie the biological specificities of these species. Furthermore, we highlight a number of Plasmodium kinases that have a surprisingly high level of similarity with their human counterparts and therefore not well suited as targets for drug discovery.

Conclusions

Direct comparison of the kinomes of Homo sapiens, P. falciparum and P. vivax sheds additional light on the previously documented divergence of many P. falciparum and P. vivax kinases from those of their human host. We provide the first direct kinome comparison between the phylogenetically distinct species of P. falciparum and P. vivax, illustrating the key similarities and differences which must be considered in the context of kinase-directed antimalarial drug discovery, and discuss the divergences and similarities between the human and Plasmodium kinomes to inform future searches for selective antimalarial intervention.
Transcriptome-wide N6-methyladenine methylation in granulosa cells of women with decreased ovarian reserve
Authors: Liu Chang , Li Linshuang , Yang Bo , Zhao Yiqing , Dong Xiyuan , Zhu Lixia , Ren Xinling , Huang Bo , Yue Jing , Jin Lei , Zhang Hanwang , Wang Lan
Published: March 2022

Background

The emerging epitranscriptome plays an essential role in female fertility. As the most prevalent internal mRNA modification, N6-methyladenine (m6A) methylation regulate mRNA fate and translational efficiency. However, whether m6A methylation was involved in the aging-related ovarian reserve decline has not been investigated. Herein, we performed m6A transcriptome-wide profiling in the ovarian granulosa cells of younger women (younger group) and older women (older group).

Results

m6A methylation distribution was highly conserved and enriched in the CDS and 3’UTR region. Besides, an increased number of m6A methylated genes were identified in the older group. Bioinformatics analysis indicated that m6A methylated genes were enriched in the FoxO signaling pathway, adherens junction, and regulation of actin cytoskeleton. A total of 435 genes were differently expressed in the older group, moreover, 58 of them were modified by m6A. Several specific genes, including BUB1B, PHC2, TOP2A, DDR2, KLF13, and RYR2 which were differently expressed and modified by m6A, were validated using qRT-PCR and might be involved in the decreased ovarian functions in the aging ovary.

Conclusions

Hence, our finding revealed the transcriptional significance of m6A modifications and provide potential therapeutic targets to promote fertility reservation for aging women.
Estimation of invasive Group B Streptococcus disease risk in young infants from case-control serological studies
Authors: Izu Alane , Kwatra Gaurav , Madhi Shabir A. , Rigat Fabio
Published: March 2022

Background

Group B Streptococcus (GBS) infections are a major cause of invasive disease (IGbsD) in young infants and cause miscarriage and stillbirths. Immunization of pregnant women against GBS in addition to intrapartum antibiotic prophylaxis could prevent disease. Establishing accurate serological markers of protection against IGbsD could enable use of efficient clinical trial designs for vaccine development and licensure, without needing to undertake efficacy trials in prohibitively large number of mother-infant dyads. The association of maternal naturally acquired serotype-specific anti-capsular antibodies (IgG) against serotype-specific IGbsD in their infants has been studied in case-control studies. The statistical models used so far to estimate IGbsD risk from these case-control studies assumed that the antibody concentrations measured sharing the same disease status are sampled from the same population, not allowing for differences between mothers colonised by GBS and mothers also potentially infected (e.g urinary tract infection or chorioamnionitis) by GBS during pregnancy. This distinction is relevant as infants born from infected mothers with occult medical illness may be exposed to GBS prior to the mother developing antibodies measured in maternal or infant sera.

Methods

Unsupervised mixture model averaging (MMA) is proposed and applied here to accurately estimate infant IGbsD risk from case-control study data in presence or absence of antibody concentration subgroups potentially associated to maternal GBS carriage or infection. MMA estimators are compared to non-parametric disease risk estimators in simulation studies and by analysis of two published GBS case-control studies.

Results

MMA provides more accurate relative risk estimates under a broad range of data simulation scenarios and more accurate absolute disease risk estimates when the proportion of IGbsD cases with high antibody levels is not ignorable. MMA estimates of the relative and absolute disease risk curves are more amenable to clinical interpretation compared to non-parametric estimates with no detectable overfitting of the data. Antibody concentration thresholds predictive of protection from infant IGbsD estimated by MMA from maternal and infant sera are consistent with non-parametric estimates.

Conclusions

MMA is a flexible and robust method for design, accurate analysis and clinical interpretation of case-control studies estimating relative and absolute IGbsD risk from antibody concentrations measured at or after birth.
Costing of an Australian general practice COVID-19 drive-through testing and respiratory clinic
Authors: Abraham Patrick , Manski-Nankervis Jo-Anne , Biezen Ruby , Hallinan Christine Mary , Gibney Katherine B. , Sanci Lena , Ride Jemimah
Published: March 2022

Background

Responding to the COVID-19 pandemic requires safe and efficient testing on a large scale over a prolonged period. Outpatient testing facilities can clinically assess and test symptomatic individuals and test asymptomatic contacts. This study identified the resources required to establish and maintain an Australian general practitioner (GP) led testing facility that combined a respiratory clinic for clinical assessment and testing with a drive-through testing facility.

Methods

Data were taken from clinic administrative records to identify the number of patients tested over the period April-June 2020. An independent auditor’s report identified the resources used in establishing, running, and staffing both clinics for the same period. Analyses were performed using the minimum and maximum daily throughput to understand the effect of demand on price per sample collected.

Results

The respiratory clinic tested an average of 19 patients per day, at an estimated cost of $340.04 AUD. This varied to $687.99 AUD during the lowest demand scenario, and $281.04 AUD during the high demand scenario. The drive-through clinic tested an average of 47 patients per day, at an estimated cost of $153.57 AUD. This varied to $279.51 AUD during the lowest demand scenario, and $99.92 AUD during the high demand scenario.

Conclusion

This study provides insight into the cost of testing at a drive through and respiratory clinic in Australia. The evidence highlights importance of considering variation in demand and the impact on efficiency, particularly where resource use is fixed in the short term.
Effect of clinical versus administrative data definitions on the epidemiology of C. difficile among hospitalized individuals with IBD: a population-based cohort study
Authors: Shaffer Seth R. , Nugent Zoann , Bernstein Charles N. , Walkty Andrew , Singh Harminder
Published: March 2022

Background

Hospitalization admissions and discharge databases (DAD) using the International Classification of Diseases (ICD) codes are often used to describe the epidemiology of Clostridioides difficile infections (CDI) among those with Inflammatory bowel disease (IBD), even though DAD CDI definition can miss many cases of CDI. There are no data comparing the assessment of the epidemiology of CDI among those with IBD by DAD versus laboratory diagnosis. We used a population-based dataset to determine the effect of using DAD versus laboratory CDI diagnosis on CDI assessment among those with IBD.

Methods

We linked the University of Manitoba IBD Epidemiology Database to the provincial CDI laboratory dataset for the years 2005–2014. Time trends of CDI were assessed using joinpoint analyses. We used stratified logistic regression analysis to assess factors associated with CDI among individuals with IBD.

Results

Time trends of CDI among hospitalized individuals with IBD were similar when using DAD or the laboratory CDI diagnosis. Prior hospital admission and antibiotic exposure were associated with CDI using either of the CDI definitions, 5-ASA use was associated with CDI using DAD but not laboratory diagnosis, whereas corticosteroid exposure was associated with laboratory-based CDI diagnosis. Using laboratory results as gold standard, DAD had a sensitivity and specificity of 75.4% and 99.6% for CDI among those with IBD.

Conclusions

Using ICD codes in the DAD for CDI provides similar epidemiological time trend patterns as identifying CDI in the laboratory dataset. Hence, ICD codes are reliable to determine CDI epidemiology among hospitalized individuals with IBD.
Risk factors for long-term survival in patients with ypN+ M0 rectal cancer after radical anterior resection
Authors: Zeman Marcin , Skałba Władysław , Szymański Piotr , Hadasik Grzegorz , Żaworonkow Dmytro , Walczak Dominik A. , Czarniecka Agnieszka
Published: March 2022

Background

Regional lymph node metastases are the main adverse prognostic factor in patients with rectal cancer without distant metastases. There are discrepancies, however, regarding additional risk factors in the group of ypN + M0 patients. The purpose of the study was to assess clinical and pathological factors affecting long-term oncological outcomes in the group of ypN + M0 patients after radical rectal anterior resection.

Methods

112 patients with ypN + M0 rectal cancer after neoadjuvant therapy and radical anterior resection were subject to a retrospective analysis. The effect of potential factors on survival was assessed with the use of Kaplan–Meier curves together with a log-rank test and multiple factor Cox proportional hazards model.

Results

In the multiple factor Cox analysis, adverse factors affecting disease-free survival (DFS) were: the use of angiotensin-converting enzyme inhibitors (ACEIs) (hazard ratio HR: 3.11, 95% CI 1.01–9.56, p = 0.047), presence of perineural invasion (HR: 7.27, 95% CI 2.74–19.3, p < 0.001) and occurrence of postoperative complications (HR: 6.79, 95% CI 2.09–22.11, p = 0.001), while a positive factor was the negative lymph node (NLN) count > 7 (HR: 0.33, 95% CI 0.12–0.88, p = 0.026). In the disease-specific survival (DSS) analysis, an adverse factor was the use of ACEIs (HR: 4.275, 95% CI 1.44–12.694, p = 0.009), while a positive effect was caused by NLN > 5 (HR: 0.22, 95% CI 0.082–0.586, p = 0.002).

Conclusions

The use of ACEIs may have a negative effect on long-term treatment outcomes in patients with ypN + M0 rectal cancer. In this group of patients, the NLN count seems to be an important prognostic factor, as well.
Comparison of operative outcomes between monopolar and bipolar coagulation in hepatectomy: a propensity score-matched analysis in a single center
Authors: Muraki Ryuta , Morita Yoshifumi , Ida Shinya , Kitajima Ryo , Furuhashi Satoru , Takeda Makoto , Kikuchi Hirotoshi , Hiramatsu Yoshihiro , Fukazawa Atsuko , Sakaguchi Takanori , Fukushima Mayu , Okada Eisaku , Takeuchi Hiroya
Published: March 2022

Background

Various hemostatic devices have been utilized to reduce blood loss during hepatectomy. Nonetheless, a comparison between monopolar and bipolar coagulation, particularly their usefulness or inferiority, has been poorly documented. The aim of this study is to reveal the characteristics of these hemostatic devices.

Methods

A total of 264 patients who underwent open hepatectomy at our institution from January 2009 to December 2018 were included. Monopolar and bipolar hemostatic devices were used in 160 (monopolar group) and 104 (bipolar group) cases, respectively. Operative outcomes and thermal damage to the resected specimens were compared between these groups using propensity score matching according to background factors. Multivariate logistic regression analysis was performed to identify predictive factors for postoperative complications.

Results

After propensity score matching, 73 patients per group were enrolled. The monopolar group had significantly lower total operative time (239 vs. 275 min; P = 0.013) and intraoperative blood loss (487 vs. 790 mL; P < 0.001). However, the incidence rates of ascites (27.4% vs. 8.2%; P = 0.002) and grade ≥ 3 intra-abdominal infection (12.3% vs. 2.7%; P = 0.028) were significantly higher in the monopolar group. Thermal damage to the resected specimens was significantly longer in the monopolar group (4.6 vs. 1.2 mm; P < 0.001). Use of monopolar hemostatic device was an independent risk factor for ascites (odds ratio, 5.626, 95% confidence interval 1.881–16.827; P = 0.002) and severe intra-abdominal infection (odds ratio, 5.905, 95% confidence interval 1.096–31.825; P = 0.039).

Conclusions

Although monopolar devices have an excellent hemostatic ability, they might damage the remnant liver. The use of monopolar devices can be one of the factors that increase the frequency of complications.
Impact of walking states, self-reported daily walking amount and age on the gait of older adults measured with a smart-phone app: a pilot study
Authors: Zhong Runting , Gao Tian
Published: March 2022

Background

Smartphones provide a cost-effective avenue for gait assessment among older adults in the community. The purpose of this study is to explore the impact of walking state, self-reported daily walking amount, and age on gait quality, using a smartphone application.

Methods

One hundred older adult individuals from North China, aged 73.0 ± 7.7 years, voluntarily participated in this study. They performed three walking tests: normal walking, fast walking, and visually impaired walking. Three-dimensional acceleration data for gait were obtained using the smartphone app Pocket Gait. This study used multivariate analysis of variance (MANOVA) to explore the effects of the walking state, self-reported daily walking amount, and age on the step frequency, root mean square (RMS) acceleration, step time variability, regularity, and symmetry.

Results

The walking state, self-reported daily walking amount, and age had statistically significant effects on gait quality. Compared with normal walking, the step frequency, RMS acceleration, variability, and regularity were greater in the fast-walking state, and simulated visually impaired walking did not significantly affect gait quality. Relatively older individuals had a significant decline in gait quality compared to (relatively) younger older adult individuals. Compared with older adults who walked less than 1 km a day, older adults who walked more had better gait quality.

Conclusions

The walking state, self-reported daily walking amount, and age have a significant effect on the gait quality of older adults. Walking with pigmented sunglasses can be used as a training intervention to improve gait performance. Older adult people who walk less than 1 km/day have worse gait quality compared with their counterparts.