bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Analysis of the Sensitivity of the Activated Partial Thromboplastin Time (APTT) Assay, as Used in a Large Laboratory Network, to Coagulation Factor Deficiencies
Authors: Do Louis , Favaloro Emmanuel , Pasalic Leonardo 
Published: January 2022

Abstract

Objectives
To advance knowledge in using the ex vivo method to identify factor sensitivity of the activated partial thromboplastin time (APTT), using data from a hemophilia and reference hemostasis laboratory; to evaluate application of inclusion and exclusion criteria to eliminate data outliers; and to discuss outcomes with reference to comparable studies.

Methods
An ex vivo, retrospective analysis was performed on patient samples with conjointly ordered APTT and intrinsic pathway factors (VIII, IX, XI, XII) for application to a large network of laboratories. The relationship between factor levels and APTT, before and after application of exclusion criteria, is demonstrated.

Results
Curvilinear relationships were found between all factor levels and APTTs, which demonstrated both similarities and differences with available studies. Factor sensitivity data are presented. Study strengths include large sample size and use of real-world data. Limitations include inability to exclude all residual outliers and paucity of patient samples singularly deficient in factors other than FVIII.

Conclusions
This ex vivo, retrospective analysis of the sensitivity of the APTT assay to intrinsic pathway factor deficiencies using real-world data from a hemophilia and reference hemostasis laboratory contains the largest sample size using this approach to date. The outcomes assist in informing practice in this area and can be used as a reference for further studies.
Current and investigational therapies for the treatment of refractory ventricular fibrillation
Authors: Scaturo Nicholas , Shomo Eileen , Frank Marshall 
Published: January 2022

Abstract

Purpose
Esmolol, dual sequential defibrillation, vector change defibrillation, and left stellate ganglion block are presented and reviewed for the treatment of refractory ventricular fibrillation.

Summary
Although no formal definition has been established for refractory ventricular fibrillation, the literature describes it as a pulseless ventricular arrhythmia that persists despite 3 standard defibrillation attempts, administration of amiodarone 300 mg intravenously, and provision of three 1-mg intravenous doses of epinephrine. Evolving literature surrounding resuscitation in this particular subset of cardiac arrest challenges the efficacy of traditional therapies, such as epinephrine, and suggests that other treatment modalities may improve outcomes. Case reports, case series, and small retrospective studies have pointed to benefit when utilizing a variety of therapies, namely, esmolol, dual sequential defibrillation, vector change defibrillation, or left stellate ganglion block, in patients with refractory ventricular fibrillation arrest.

Conclusion
A mounting, although limited, body of evidence suggests that esmolol, dual sequential defibrillation, vector change defibrillation, or left stellate ganglion block may be effective at terminating refractory ventricular fibrillation and improving patient outcomes. Further evidence is required before these therapies can be adopted as standard practice; however, as key members of the code response team, it is imperative for pharmacists to be familiar with the supporting evidence, safety considerations, and logistical challenges of utilizing these treatments during arrest.
A Comparison Between Ecological Momentary Assessment and the Adapted-Quick Drinking Screen: Alcohol Mixed With Energy Drinks
Authors: Johnson Sean J , Verster Joris C , Alford Chris 
Published: January 2022

Abstract

Aims
To compare alcohol consumption and risk-taking behaviours on alcohol mixed with energy drink (AMED) and alcohol-only (AO) drinking occasions collected via ecological momentary assessment (EMA) versus retrospective survey methods (adapted-Quick Drinking Screen: a-QDS).

Methods
Completing participants were 52 university students who reported AMED consumption during the 30-day data collection period. Alcohol consumption and risk-taking behaviours were captured for recreational AMED and AO consumption occasions using a smartphone-based app across 30 days. Data were aggregated for comparison with the a-QDS conducted at the end of data collection.

Results
Irrespective of data collection method, alcohol was consumed more frequently and at higher quantities on the heaviest drinking occasions when consumed alone compared with when it was mixed with energy drinks. Consistent with this finding, more risk-taking behaviours were experienced on AO occasions compared with AMED occasions. Compared with the a-QDS, the quantity of alcohol consumed on the average and heaviest drinking occasion was significantly higher when reported via EMA. This was consistent across both AO and AMED drinking occasions.

Conclusion
EMA provides a more valid measure of consumption quantity compared with retrospective recall, which was susceptible to under-reporting, although this was not differentially affected across consumption occasions. In line with previous research, this study demonstrated that mixing alcohol with energy drinks does not increase alcohol consumption or risk-taking behaviours.
Isolation of purple nonsulfur bacteria from the digestive tract of ayu (Plecoglossus altivelis)
Authors: Koga Aoi , Yamasaki Takumi , Hayashi Shuhei , Yamamoto Shinjiro , Miyasaka Hitoshi 
Published: January 2022

ABSTRACTPurple nonsulfur bacteria (PNSB) reportedly have probiotic effects in fish, but whether they are indigenous in the digestive tract of fish is a question that requires answering. We attempted to isolate PNSB from the digestive tract of ayu (Plecoglossus altivelis) from the Kuma River (Kumamoto, Japan) and successfully isolated 12 PNSB strains. All the isolated PNSB belonged to the genus Rhodopseudomonas. Five Rhodopseudomonas strains were also isolated from the soil samples collected along the Kuma River. The phylogenetic tree based on the partial sequence of pufLM gene indicated that the PNSB from ayu and soil were similar. The effects of NaCl concentration in growth medium on growth were also compared between the PNSB from ayu and soil. The PNSB from ayu showed a better growth performance at a higher NaCl concentration, suggesting that the intestinal tract of ayu, a euryhaline fish, might provide suitable environment for halophilic microorganisms.
A weighted bilinear neural collaborative filtering approach for drug repositioning
Authors: Meng Yajie , Lu Changcheng , Jin Min , Xu Junlin , Zeng Xiangxiang , Yang Jialiang 
Published: January 2022

AbstractDrug repositioning is an efficient and promising strategy for traditional drug discovery and development. Many research efforts are focused on utilizing deep-learning approaches based on a heterogeneous network for modeling complex drug–disease associations. Similar to traditional latent factor models, which directly factorize drug–disease associations, they assume the neighbors are independent of each other in the network and thus tend to be ineffective to capture localized information. In this study, we propose a novel neighborhood and neighborhood interaction-based neural collaborative filtering approach (called DRWBNCF) to infer novel potential drugs for diseases. Specifically, we first construct three networks, including the known drug–disease association network, the drug–drug similarity and disease–disease similarity networks (using the nearest neighbors). To take the advantage of localized information in the three networks, we then design an integration component by proposing a new weighted bilinear graph convolution operation to integrate the information of the known drug–disease association, the drug’s and disease’s neighborhood and neighborhood interactions into a unified representation. Lastly, we introduce a prediction component, which utilizes the multi-layer perceptron optimized by the α-balanced focal loss function and graph regularization to model the complex drug–disease associations. Benchmarking comparisons on three datasets verified the effectiveness of DRWBNCF for drug repositioning. Importantly, the unknown drug–disease associations predicted by DRWBNCF were validated against clinical trials and three authoritative databases and we listed several new DRWBNCF-predicted potential drugs for breast cancer (e.g. valrubicin and teniposide) and small cell lung cancer (e.g. valrubicin and cytarabine).
Boar spermadhesin AWN: novel insights in its binding behavior and localization on sperm
Authors: Kroh Pascal D , Braun Beate C , Liu Fan , Müller Peter , Müller Karin 
Published: January 2022

Abstract
As a major spermadhesin first found in the seminal plasma (SP) of boars, AWN is described to fulfil a variety of reproduction related tasks. Although being the best investigated boar spermadhesin, information about its interaction with membranes is inconsistent. In this regard, previous reports locate AWN either inside or on the surface of sperm cells and at different regions, depending on the method and antibody used. Here, we localize native AWN (natAWN) in/on epididymal, ejaculated, capacitated, and acrosome-reacted boar sperm using epifluorescence and electron microscopy as well as an analysis of potential lipid-binding partners of natAWN and recombinant AWN (recAWN). By applying a custom-made anti-AWN antibody, localization of AWN in the equatorial segment (EQS) of ejaculated, capacitated, and acrosome-reacted boar sperm was discovered. Electron microscopy showed that AWN is localized both on the sperm surface and on the cytoplasmic side of the plasma membrane and in close vicinity to the nuclear and both acrosomal membranes of sperm. Analysis of epididymal sperm indicated migration of AWN from the retral postacrosomal part to the EQS during the epididymal passage. In contrast to hypotheses claiming a specific association of AWN to phosphatidylethanolamine (PE) and in line with our previous study describing an interaction with phosphatidic acid (PA), the current results show a rather electrostatically driven binding mechanism of AWN to negative lipids. In conclusion, this work provides new insights into the arrangement of AWN in the EQS, which suggest a possible role in sperm–oocyte fusion.
Estimation and false discovery control for the analysis of environmental mixtures
Authors: Samanta Srijata , Antonelli Joseph 
Published: January 2022

SummaryThe analysis of environmental mixtures is of growing importance in environmental epidemiology, and one of the key goals in such analyses is to identify exposures and their interactions that are associated with adverse health outcomes. Typical approaches utilize flexible regression models combined with variable selection to identify important exposures and estimate a potentially nonlinear relationship with the outcome of interest. Despite this surge in interest, no approaches to date can identify exposures and interactions while controlling any form of error rates with respect to exposure selection. We propose two novel approaches to estimating the health effects of environmental mixtures that simultaneously (i) estimate and provide valid inference for the overall mixture effect and (ii) identify important exposures and interactions while controlling the false discovery rate (FDR). We show that this can lead to substantial power gains to detect weak effects of environmental exposures. We apply our approaches to a study of persistent organic pollutants and find that controlling the FDR leads to substantially different conclusions.
Patho-immunological mechanisms of vitiligo: the role of the innate and adaptive immunities and environmental stress factors
Authors: Faraj Safa , Kemp Elizabeth Helen , Gawkrodger David John 
Published: January 2022

AbstractEpidermal melanocyte loss in vitiligo, triggered by stresses ranging from trauma to emotional stress, chemical exposure or metabolite imbalance, to the unknown, can stimulate oxidative stress in pigment cells, which secrete damage-associated molecular patterns that then initiate innate immune responses. Antigen presentation to melanocytes leads to stimulation of autoreactive T-cell responses, with further targeting of pigment cells. Studies show a pathogenic basis for cellular stress, innate immune responses and adaptive immunity in vitiligo. Improved understanding of the aetiological mechanisms in vitiligo has already resulted in successful use of the Jak inhibitors in vitiligo. In this review, we outline the current understanding of the pathological mechanisms in vitiligo and locate loci to which therapeutic attack might be directed.
Predictive biomarker modeling of pediatric atopic dermatitis severity based on longitudinal serum collection
Authors: Engle Sarah M , Chang Ching-Yun , Ulrich Benjamin J , Satterwhite Allyson , Hayes Tristan , Robling Kim , Sissons Sean E , Schmitz Jochen , Tepper Robert S , Kaplan Mark H , Sims Jonathan T 
Published: January 2022

AbstractThe pathogenesis of atopic dermatitis (AD) results from complex interactions between environmental factors, barrier defects, and immune dysregulation resulting in systemic inflammation. Therefore, we sought to characterize circulating inflammatory profiles in pediatric AD patients and identify potential signaling nodes which drive disease heterogeneity and progression. We analyzed a sample set of 87 infants that were at high risk for atopic disease based on AD diagnoses. Clinical parameters, serum, and peripheral blood mononuclear cells (PBMCs) were collected upon entry, and at 1 and 4 years later. Within patient serum, 126 unique analytes were measured using a combination of multiplex platforms and ultrasensitive immunoassays. We assessed the correlation of inflammatory analytes with AD severity (SCORAD). Key biomarkers, such as IL-13 (rmcorr = 0.47) and TARC/CCL17 (rmcorr = 0.37), among other inflammatory signals, significantly correlated with SCORAD across all timepoints in the study. Flow cytometry and pathway analysis of these analytes implies that CD4 T-cell involvement in type 2 immune responses was enhanced at the earliest time point (year 1) relative to the end of study collection (year 5). Importantly, forward selection modeling identified 18 analytes in infant serum at study entry which could be used to predict change in SCORAD 4 years later. We have identified a pediatric AD biomarker signature linked to disease severity which will have predictive value in determining AD persistence in youth and provide utility in defining core systemic inflammatory signals linked to pathogenesis of atopic disease.
Molecular neuroimaging of inflammation in HIV
Authors: Alagaratnam Jasmini , Winston Alan 
Published: January 2022

Abstract
People with HIV now have near-normal life expectancies due to the success of effective combination antiretroviral therapy (cART). Following cART initiation, immune recovery occurs, and opportunistic diseases become rare. Despite this, high rates of non-infectious comorbidities persist in treated people with HIV, hypothesized to be related to persistent immuno-activation. One such comorbidity is cognitive impairment, which may partly be driven by ongoing neuro-inflammation in otherwise effectively treated people with HIV. In order to develop therapeutic interventions to address neuro-inflammation in effectively treated people with HIV, a deeper understanding of the pathogenic mechanisms driving persistent neuro-inflammatory responses and the ability to better characterize and measure neuro-inflammation in the central nervous system is required. This review highlights recent advances in molecular neuroimaging techniques which have the potential to assess neuro-inflammatory responses within the central nervous system in HIV disease. Proton magnetic resonance spectroscopy (1H-MRS) has been utilized to assess neuro-inflammatory responses since early in the HIV pandemic and shows promise in recent studies assessing different antiretroviral regimens. 1H-MRS is widely available in both resource-rich and some resource-constrained settings and is relatively inexpensive. Brain positron emission tomography (PET) imaging using Translocator Protein (TSPO) radioligands is a rapidly evolving field; newer TSPO-radioligands have lower signal-to-noise ratio and have the potential to localize neuro-inflammation within the brain in people with HIV. As HIV therapeutics evolve, people with HIV continue to age and develop age-related comorbidities including cognitive disorders. The use of novel neuroimaging modalities in the field is likely to advance in order to rapidly assess novel therapeutic interventions and may play a role in future clinical assessments.
Seroconversion following COVID-19 vaccination: can we optimize protective response in CD20-treated individuals?
Authors: Baker David , MacDougall Amy , Kang Angray S , Schmierer Klaus , Giovannoni Gavin , Dobson Ruth 
Published: January 2022

AbstractAlthough there is an ever-increasing number of disease-modifying treatments for relapsing multiple sclerosis (MS), few appear to influence coronavirus disease 2019 (COVID-19) severity. There is concern about the use of anti-CD20-depleting monoclonal antibodies, due to the apparent increased risk of severe disease following severe acute respiratory syndrome corona virus two (SARS-CoV-2) infection and inhibition of protective anti-COVID-19 vaccine responses. These antibodies are given as maintenance infusions/injections and cause persistent depletion of CD20+ B cells, notably memory B-cell populations that may be instrumental in the control of relapsing MS. However, they also continuously deplete immature and mature/naïve B cells that form the precursors for infection-protective antibody responses, thus blunting vaccine responses. Seroconversion and maintained SARS-CoV-2 neutralizing antibody levels provide protection from COVID-19. However, it is evident that poor seroconversion occurs in the majority of individuals following initial and booster COVID-19 vaccinations, based on standard 6 monthly dosing intervals. Seroconversion may be optimized in the anti-CD20-treated population by vaccinating prior to treatment onset or using extended/delayed interval dosing (3–6 month extension to dosing interval) in those established on therapy, with B-cell monitoring until (1–3%) B-cell repopulation occurs prior to vaccination. Some people will take more than a year to replete and therefore protection may depend on either the vaccine-induced T-cell responses that typically occur or may require prophylactic, or rapid post-infection therapeutic, antibody or small-molecule antiviral treatment to optimize protection against COVID-19. Further studies are warranted to demonstrate the safety and efficacy of such approaches and whether or not immunity wanes prematurely as has been observed in the other populations.
IgLON5 autoimmunity tested positive in patients with isolated chronic insomnia disease
Authors: Aghelan Zahra , Karima Saeed , Ghadami Mohammad Rasoul , Khazaie Habibolah , Bahrehmand Fariborz , Vaisi-Raygani Asad , Abtahi Seyed Hosein , Khodarahmi Reza 
Published: January 2022

Abstract
In the patients with neurological autoimmune diseases such as anti-IgLON5 disease, insomnia symptoms are very common. Clinical diagnosis of the anti-IgLON5 disease is usually made when neurodegenerative processes have occurred. To find the early signs of anti-IgLON5 disease, we evaluate the presence of IgLON5 autoantibodies in the serum of patients with chronic insomnia disease. Based on video-polysomnography, 22 individuals with isolated chronic insomnia disease were found. A control group of 22 healthy people was chosen using the Pittsburgh Sleep Quality Index (PSQI). An indirect immunofluorescence cell-based test of serum anti-IgLON5 antibodies was used to investigate IgLON5 autoimmunity. Anti-IgLON5 antibodies were detected in the serum of four of these patients with the titer of 1/10. The presence of IgLON5 autoantibodies in some patients with chronic insomnia disease can be considered a causing factor of insomnia which can be effective in more specific treatments of these patients. Moreover, the recognition of anti-IgLON5 disease in the early stages and before the progression of tauopathies can be useful in effective and timely treatment.
Diagnosis of HLH: two siblings, two distinct genetic causes
Authors: Escaron Claire , Ralph Elizabeth , Bibi Shahnaz , Visser Johannes , Aricò Maurizio , Rao Kanchan , Veys Paul , Gilmour Kimberly 
Published: January 2022

Abstract
This report highlights case of two siblings who developed haemophagocytic lymphohystiocytosis due to distinct genetic abnormalities. Though their presentation was clinically similar, the cases demonstrate that a shared genetic diagnosis among siblings cannot be assumed.
Macrophages in ovarian cancer and their interactions with monoclonal antibody therapies
Authors: Osborn Gabriel , Stavraka Chara , Adams Rebecca , Sayasneh Ahmad , Ghosh Sharmistha , Montes Ana , Lacy Katie E , Kristeleit Rebecca , Spicer James , Josephs Debra H , Arnold James N , Karagiannis Sophia N 
Published: January 2022

Abstract
The unmet clinical need for effective treatments in ovarian cancer has yet to be addressed using monoclonal antibodies (mAbs), which have largely failed to overcome tumour-associated immunosuppression, restrict cancer growth, and significantly improve survival. In recent years, experimental mAb design has moved away from solely targeting ovarian tumours and instead sought to modulate the wider tumour microenvironment (TME). Tumour-associated macrophages (TAMs) may represent an attractive therapeutic target for mAbs in ovarian cancer due to their high abundance and close proximity to tumour cells and their active involvement in facilitating several pro-tumoural processes. Moreover, the expression of several antibody crystallisable fragment (Fc) receptors and broad phenotypic plasticity of TAMs provide opportunities to modulate TAM polarisation using mAbs to promote anti-tumoural phenotypes. In this review, we discuss the role of TAMs in ovarian cancer TME and the emerging strategies to target the contributions of these cells in tumour progression through the rationale design of mAbs.
Potential role of BAY11-7082, a NF-κB blocker inhibiting experimental autoimmune encephalomyelitis in C57BL/6J mice via declining NLRP3 inflammasomes
Authors: Lang Yue , Chu Fengna , Liu Lingling , Zheng Chao , Li Chunrong , Shen Donghui , Liu Shan , Zhang Weiguanliu , Cui Li , Zhu Jie 
Published: January 2022

Abstract
Multiple sclerosis (MS) is an inflammatory autoimmune demyelinating disease of the central nervous system. NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is implicated in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the exact mechanism by which NLRP3 inflammasome is involved in the development of MS and EAE is not clear. NF-kappaB (NF-κB) is associated with the activity of NLRP3 inflammasomes, but the role of NF-κB is controversial. We sought to demonstrate that both NF-κB and NLRP3 contribute to development of MS and EAE, and NF-κB pathway is positively correlated with NLRP3 activation in EAE. The inhibitor of NF-κB and NLRP3, BAY11-7082, can prevent and treat EAE. BAY11-7082 (5 and 20 mg/kg/i.p.) was intraperitoneally administered to EAE mice at the time of second injection of pertussis toxin (BAY11-7082 prevention group) or at the onset of symptoms (BAY11-7082 treatment group). mRNA expressions of NLRP3 were determined by qPCR. Protein expressions of NLRP3, NF-κB p65, and phosphorylated p65 were determined by western blotting. Serum levels of inflammatory cytokines were measured by cytometric bead array. Mice treated with BAY11-7082 (both prevention and treatment groups) showed lower clinical scores and attenuated pathological changes. NLRP3 inflammasome and activity of NF-κB in spinal cord of EAE mice was higher than that in control group. However, the level of NLRP3 inflammasome decreased in BAY11-7082 prevention and treatment groups. BAY11-7082 is a promising therapeutic agent for MS. NLRP3 activation in EAE maybe related with NF-κB pathway.