bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting Myd88 using peptide-loaded mesenchymal stem cell membrane-derived synthetic vesicles to treat systemic inflammation
Authors: Park Kyong-Su , Bergqvist Markus , Lässer Cecilia , Lötvall Jan
Published: October 2022

Mesenchymal stem cells (MSC) secrete extracellular vesicles (EV) with a regenerative profile, and an increasing number of studies have focused on the utilization of MSC-EV for therapeutic drug delivery. However, EV are usually produced by cells in low quantities and are packed with numerous cytoplasmic components, which may be unfavorable for further drug loading. In this study, we developed a simple process for generating membrane vesicles directly from the cells, which we refer to as synthetic eukaryotic vesicles (SyEV). We hypothesized that MSC-derived SyEV can be efficiently loaded with an anti-inflammatory drug and the loaded vesicles can strongly suppress the systemic inflammation induced by bacterial outer membrane vesicles (OMV). SyEV were generated from MSC membranes through serial extrusion of the cells, ionic stress, and subsequent vesiculation of the membrane sheets, leading to high yield and purity of the SyEV with few cytosolic components remaining. When these SyEV were given to macrophages or mice exposed to OMV, the release of pro-inflammatory cytokines was similarly attenuated comparable to treatment with natural EV. We then loaded the SyEV with large numbers of peptides targeting Myd88 and observed enhanced therapeutic potential of the loaded vesicles in OMV-induced macrophages. Further, in vivo experiments showed that the peptide-encapsulated MSC-SyEV suppressed cytokine production synergistically. Taken together, these findings suggest that SyEV-based therapeutics is a highly interesting platform for delivering an advanced therapeutic drug for the treatment of systemic inflammation without severe side effects.
Trimethylamine, a gut bacteria metabolite and air pollutant, increases blood pressure and markers of kidney damage including proteinuria and KIM-1 in rats
Authors: Maksymiuk Klaudia M. , Szudzik Mateusz , Gawryś-Kopczyńska Marta , Onyszkiewicz Maksymilian , Samborowska Emilia , Mogilnicka Izabella , Ufnal Marcin
Published: October 2022

Background

Trimethylamine oxide (TMAO) is a biomarker in cardiovascular and renal diseases. TMAO originates from the oxidation of trimethylamine (TMA), a product of gut microbiota and manufacturing industries-derived pollutant, by flavin monooxygenases (FMOs). The effect of chronic exposure to TMA on cardiovascular and renal systems is undetermined.

Methods

Metabolic, hemodynamic, echocardiographic, biochemical and histopathological evaluations were performed in 12-week-old male SPRD rats receiving water (controls) or TMA (200 or 500 µM/day) in water for 18 weeks. TMA and TMAO levels, the expression of FMOs and renin-angiotensin system (RAS) genes were evaluated in various tissues.

Results

In comparison to controls, rats receiving high dose of TMA had significantly increased arterial systolic blood pressure (126.3 ± 11.4 vs 151.2 ± 19.9 mmHg; P = 0.01), urine protein to creatinine ratio (1.6 (1.5; 2.8) vs 3.4 (3.3; 4.2); P = 0.01), urine KIM-1 levels (2338.3 ± 732.0 vs. 3519.0 ± 953.0 pg/mL; P = 0.01), and hypertrophy of the tunica media of arteries and arterioles (36.61 ± 0.15 vs 45.05 ± 2.90 µm, P = 0.001 and 18.44 ± 0.62 vs 23.79 ± 2.60 µm, P = 0.006; respectively). Mild degeneration of renal bodies with glomerulosclerosis was also observed. There was no significant difference between the three groups in body weight, water-electrolyte balance, echocardiographic parameters and RAS expression. TMA groups had marginally increased 24 h TMA urine excretion, whereas serum levels and 24 h TMAO urine excretion were increased up to 24-fold, and significantly increased TMAO levels in the liver, kidneys and heart. TMA groups had lower FMOs expression in the kidneys.

Conclusions

Chronic exposure to TMA increases blood pressure and increases markers of kidney damage, including proteinuria and KIM-1. TMA is rapidly oxidized to TMAO in rats, which may limit the toxic effects of TMA on other organs.
ALDH7A1 rs12514417 polymorphism may increase ischemic stroke risk in alcohol-exposed individuals
Authors: Lin Chun-Hsiang , Nfor Oswald Ndi , Ho Chien-Chang , Hsu Shu-Yi , Tantoh Disline Manli , Liaw Yi-Chia , Mochly-Rosen Daria , Chen Che-Hong , Liaw Yung-Po
Published: October 2022

Background:

Epidemiological studies have identified common risk factors for cerebral stroke worldwide. Some of these factors include hypertension, diabetes, smoking, excessive drinking, and dyslipidemia. It is important to note, however, that genetic factors can also contribute to the occurrence of stroke. Here, we evaluated the association of ischemic stroke with rs12514417 polymorphism of the alcohol metabolizing gene, aldehyde dehydrogenase 7A1 (ALDH7A1) and alcohol consumption.

Methods:

Taiwan Biobank (TWB) data collected between 2008 and 2015 were available for 17,985 subjects. The odd ratios for stroke were obtained using logistic regression models.

Results:

Among eligible subjects (n = 17,829), 897 had ischemic stroke and 70 had hemorrhagic stroke. Subjects with ischemic stroke were older (mean ± SE, 58.45 ± 8.19 years vs. 48.33 ± 10.89 years, p < 0.0001) and had a higher body mass index (BMI) than the stroke-free individuals. The risk of ischemic stroke was significantly higher among subjects with the ALDH7A1 rs12514417 TG + GG genotype who also consumed alcohol at least 150 ml/week (odds ratio (OR), 1.79; 95% confidence interval (CI), 1.18–2.72). We found that rs12514417 genotype and alcohol consumption (at least 150 ml/week) showed a significant interaction (p for interaction = 0.0266). Stratification based on alcohol exposure and ALDH7A1 rs12514417 genotypes indicated that ischemic stroke risk was significantly higher among alcohol drinkers with the TG + GG genotype than in those with the TT genotype (OR, 1.64, 95% CI: 1.15–2.33).

Conclusion:

Our study suggests that the combination of ALDH7A1 rs12514417 TG + GG genotype and alcohol exposure of at least 150 ml/week may increase the risk of ischemic stroke in Taiwanese adults.
The choroid plexus: a door between the blood and the brain for tissue-type plasminogen activator
Authors: Zuba Vincent , Furon Jonathane , Bellemain-Sagnard Mathys , Martinez de Lizarrondo Sara , Lebouvier Laurent , Rubio Marina , Hommet Yannick , Gauberti Maxime , Vivien Denis , Ali Carine
Published: October 2022

Background

In the vascular compartment, the serine protease tissue-type plasminogen activator (tPA) promotes fibrinolysis, justifying its clinical use against vasculo-occlusive diseases. Accumulating evidence shows that circulating tPA (endogenous or exogenous) also controls brain physiopathological processes, like cerebrovascular reactivity, blood–brain barrier (BBB) homeostasis, inflammation and neuronal fate. Whether this occurs by direct actions on parenchymal cells and/or indirectly via barriers between the blood and the central nervous system (CNS) remains unclear. Here, we postulated that vascular tPA can reach the brain parenchyma via the blood-cerebrospinal fluid barrier (BCSFB), that relies on choroid plexus (CP) epithelial cells (CPECs).

Methods

We produced various reporter fusion proteins to track tPA in primary cultures of CPECs, in CP explants and in vivo in mice. We also investigated the mechanisms underlying tPA transport across the BCSFB, with pharmacological and molecular approaches.

Results

We first demonstrated that tPA can be internalized by CPECs in primary cultures and in ex vivo CPs explants. In vivo, tPA can also be internalized by CPECs both at their basal and apical sides. After intra-vascular administration, tPA can reach the cerebral spinal fluid (CSF) and the brain parenchyma. Further investigation allowed discovering that the transcytosis of tPA is mediated by Low-density-Lipoprotein Related Protein-1 (LRP1) expressed at the surface of CPECs and depends on the finger domain of tPA. Interestingly, albumin, which has a size comparable to that of tPA, does not normally cross the CPs, but switches to a transportable form when grafted to the finger domain of tPA.

Conclusions

These findings provide new insights on how vascular tPA can reach the brain parenchyma, and open therapeutic avenues for CNS disorders.
miR-124-3p sabotages lncRNA MALAT1 stability to repress chondrocyte pyroptosis and relieve cartilage injury in osteoarthritis
Authors: Rozi Rigbat , Zhou Yubo , Rong Kai , Chen Pingbo
Published: October 2022

Background

Osteoarthritis (OA) is a prevalent inflammatory joint disorder. microRNAs (miRNAs) are increasingly involved in OA.

Aim

Our study is proposed to clarify the role of miR-124-3p in chondrocyte pyroptosis and cartilage injury in OA.

Methods

OA mouse model was established via the treatment of destabilization of the medial meniscus (DMM), and the in vitro cell model was also established as mouse chondrocytes were induced by lipopolysaccharide (LPS). Mouse cartilage injury was assessed using safranin-O-fast green staining, hematoxylin–eosin staining, and OARSI grading method. Expressions of miR-124-3p, MALAT1, KLF5, and CXCL11 were determined. Cartilage injury (MMP-13, osteocalcin), inflammation (IL-6, IL-2, TNF-, IL-1β, and IL-18)- and pyroptosis-related factors (Cleaved Caspase-1 and GSDMD-N) levels were detected. Mechanically, MALAT1 subcellular localization was confirmed. The binding relationships of miR-124-3p and MALAT1 and MALAT1 and KLF5 were verified. MALAT1 half-life period was detected. Then, miR-124-3p was overexpressed using agomiR-124-3p to perform the rescue experiments with oe-MALAT1 or oe-CXCL11.

Results

miR-124-3p was downregulated in DMM mice and LPS-induced chondrocytes where cartilage injury, and increased levels of inflammation- and pyroptosis-related factors were found. miR-124-3p overexpression relieved cartilage injury and repressed chondrocyte pyroptosis. miR-124-3p bounds to MALAT1 to downregulate its stability and expression, and MALAT1 bounds to KLF5 to enhance CXCL11 transcription. Overexpression of MALAT1 or CXCL11 annulled the repressive function of miR-124-3p in chondrocyte pyroptosis.

Conclusion

miR-124-3p reduced MALAT1 stability and inhibited the binding of MALAT1 and KLF5 to downregulate CXCL11, thereby suppressing chondrocyte pyroptosis and cartilage injury in OA.
ENPP1 deletion causes mouse osteoporosis via the MKK3/p38 MAPK/PCNA signaling pathway
Authors: Wang Qiang , Gao Zhiqiang , Guo Kai , Lu Jiawei , Wang Feng , Huang Yufeng , Wu Desheng
Published: October 2022

Background

Apart from the current understanding of enzyme function, the mechanism of ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) deficiency-associated osteoporosis is unknown. We aimed to explore the changes in the expression of signaling pathways of bone tissues involved in Enpp1 deficiency.

Methods

The body weights and morphology and histology of the bones of male Enpp1 knockout (KO) and wild-type (WT) mice were assessed. The humeri of WT and Enpp1 KO mice at 12 weeks of age were subjected to high-throughput quantitative molecular measurements, and bioinformatics analysis was performed. Proteins from humeri and calvarial pre-osteoblasts (Pobs) were used to verify the differentially expressed signaling pathways and to explain the mechanism of Enpp1 deficiency-associated osteoporosis.

Results

Enpp1 KO mice had significantly lower body weight and trabecular bone mass in the hindlimbs than WT mice. Proteomics and immunoblotting showed that Enpp1 deletion downregulated the expression of the p38 mitogen-activated protein kinase (MAPK) signaling pathway in bones. Lysophosphatidic acid (LPA) was involved in activating the MKK3/p38 MAPK/PCNA pathway and proliferating Pobs in Enpp1 KO mice, whereas a p38 MAPK inhibitor suppressed the LPA-induced pro-proliferation phenotype (p < 0.05).

Conclusion

The inhibition of MKK3/p38 MAPK/PCNA pathway plays an important role in the development of osteoporosis caused by Enpp1 deficiency, and LPA partially rescued the proliferation of pre-osteoblasts via the MKK3/p38 MAPK/PCNA pathway.
Expanding a database-derived biomedical knowledge graph via multi-relation extraction from biomedical abstracts
Authors: Nicholson David N. , Himmelstein Daniel S. , Greene Casey S.
Published: October 2022

Background

Knowledge graphs support biomedical research efforts by providing contextual information for biomedical entities, constructing networks, and supporting the interpretation of high-throughput analyses. These databases are populated via manual curation, which is challenging to scale with an exponentially rising publication rate. Data programming is a paradigm that circumvents this arduous manual process by combining databases with simple rules and heuristics written as label functions, which are programs designed to annotate textual data automatically. Unfortunately, writing a useful label function requires substantial error analysis and is a nontrivial task that takes multiple days per function. This bottleneck makes populating a knowledge graph with multiple nodes and edge types practically infeasible. Thus, we sought to accelerate the label function creation process by evaluating how label functions can be re-used across multiple edge types.

Results

We obtained entity-tagged abstracts and subsetted these entities to only contain compounds, genes, and disease mentions. We extracted sentences containing co-mentions of certain biomedical entities contained in a previously described knowledge graph, Hetionet v1. We trained a baseline model that used database-only label functions and then used a sampling approach to measure how well adding edge-specific or edge-mismatch label function combinations improved over our baseline. Next, we trained a discriminator model to detect sentences that indicated a biomedical relationship and then estimated the number of edge types that could be recalled and added to Hetionet v1. We found that adding edge-mismatch label functions rarely improved relationship extraction, while control edge-specific label functions did. There were two exceptions to this trend, Compound-binds-Gene and Gene-interacts-Gene, which both indicated physical relationships and showed signs of transferability. Across the scenarios tested, discriminative model performance strongly depends on generated annotations. Using the best discriminative model for each edge type, we recalled close to 30% of established edges within Hetionet v1.

Conclusions

Our results show that this framework can incorporate novel edges into our source knowledge graph. However, results with label function transfer were mixed. Only label functions describing very similar edge types supported improved performance when transferred. We expect that the continued development of this strategy may provide essential building blocks to populating biomedical knowledge graphs with discoveries, ensuring that these resources include cutting-edge results.
The effect of backpack load on intersegmental motions of the foot and plantar pressure in individuals with mild flatfoot
Authors: Kyung Min Gyu , Bak Ppu Ri , Lim Jong Wook , Lee Dong‐Oh , Park Gil Young , Lee Dong Yeon
Published: October 2022

Background

The feet play an essential role in shock absorption, and foot posture is closely related to gait. The compensatory mechanism under heavy‐load conditions in individuals with mild flatfoot is poorly understood. In the authors' country, individuals with mild flatfoot are drafted as active‐duty soldiers and participate in military rucking wearing heavy backpacks. This study investigated the effect of backpack load on gait and foot plantar pressure and possible differences in participants with mild flatfoot. The average weight of the backpack during military rucking (approximately 20 kg), was simulated in this study.

Methods

This study prospectively enrolled 30 healthy young males, divided into a control group (CON, n = 15) and a mild low‐arched group (MLA, n = 15), based on the presence of flatfoot. Segmental foot kinematics were evaluated using a three‐dimensional multi‐segment foot model, and gait data of the temporal and spatial parameters were obtained. The dynamic plantar pressure was simultaneously measured using a pedobarography platform with gait trials. The protocol was repeated with all participants wearing 20 kg backpacks. Comparisons between the baseline and loaded states, as well as comparison between groups, were conducted.

Results

Although the cadence, gait speed, and stride length decreased in the loaded condition, step time and proportion of the stance phase increased in both groups. Although the MLA group showed more supinated and abducted positions of the forefoot and more pronated positions of the hindfoot than the CON group, the change in intersegmental foot and ankle motion in each group after backpack loading was minimal. However, the former showed a larger step width and a greater increase in contact area in the midfoot region, while the latter demonstrated a greater increase in peak pressure.

Conclusions

Individuals with mild flatfoot demonstrated significantly different gait curve patterns (waveforms) compared to the controls. In the loaded condition, the CON and MLA groups may have adopted different strategies to maintain balance during gait. We suggest that although individuals with asymptomatic mild flatfoot are drafted as active‐duty soldiers, they should be thoroughly investigated under loaded conditions, and orthoses may be helpful.
Hospital change to mixed lipid emulsion from soybean oil-based lipid emulsion for parenteral nutrition in hospitalized and critically ill adults improves outcomes: a pre–post-comparative study
Authors: Haines Krista L. , Ohnuma Tetsu , Trujillo Charles , Osamudiamen Obanor , Krishnamoorthy Vijay , Raghunathan Karthik , Wischmeyer Paul E.
Published: October 2022

Introduction

Early data suggest use of a mixed lipid emulsion (LE) with a soybean oil reduction strategy in parenteral nutrition (PN) may improve clinical outcomes. Duke University Hospital made a full switch to a Soybean oil/MCT/Olive/Fish Oil lipid (4-OLE) from pure soybean oil-based LE (Intralipid, Baxter Inc) in May 2017. Since 4-OLE has limited evidence related to its effects on clinical outcome parameters in US hospitals, evidence for clinical benefits of switching to 4-OLE is needed. Therefore, we examined the clinical utility of a hospital-wide switch to 4-OLE and its effect on patient outcomes.

Methods

We conducted a single-center retrospective cohort study among adult patients (> 18 years) requiring PN from 2016 to 2019. Our primary exposure was treatment period (1-year pre-4-OLE switch versus 2-year post). We used multivariable regression models to examine our primary outcomes, the association of treatment period with hospital length of stay (LOS), and secondary outcomes liver function, infections, and ICU LOS. Analyses were stratified into critically ill and entire adult cohort.

Results

We identified 1200 adults hospitalized patients. 28% of PN patients (n = 341) were treated pre-4-OLE switch and 72% post-4-OLE (n = 859). In the adult cohort, 4-OLE was associated with shorter hospital LOS (IRR 0.97, 95% CI 0.95–0.99, p = 0.039). The ICU cohort included 447 subjects, of which 25% (n = 110) were treated pre-4-OLE switch and 75% (n = 337) were post-switch. ICU patients receiving 4-OLE were associated with shorter hospital LOS (IRR 0.91, 95% CI 0.87–0.93, p < 0.0001), as well as a shorter ICU LOS (IRR 0.90, 95% CI 0.82–0.99, p = 0.036). 4-OLE ICU patients also had a significantly lower delta total bilirubin (− 1.6, 95% CI − 2.8 to − 0.2, p = 0.021) and reduced urinary tract infection (UTI) rates (OR 0.50, 95% CI 0.26–0.96, p = 0.038). There were no associations in AST, ALT, or total bilirubin in ICU and all adult patients.

Conclusion

4-OLE was successfully implemented and reduced soybean oil LE exposure in a large academic hospital setting. The introduction of 4-OLE was associated with reduced LOS, UTI rates, and mitigated hepatic dysfunction in critically ill patients. Overall, these findings prove a switch to a soybean oil-LE sparing strategy using 4-OLE is feasible and safe and is associated with improved clinical outcomes in adult PN patients.
Pharmacological counseling in hepatotoxicity induced by macitentan and selexipag: a case report
Authors: Lattanzio Mariangela , Ferrari Marco , Martini Stefano , Ceriani Francesca , Imporzani Andrea , Marino Franca , De Ponti Roberto , Cosentino Marco
Published: October 2022

Background

Pulmonary arterial hypertension is a progressive, debilitating condition characterized by increased resistance in the pulmonary arterial circulation. Current treatments for pulmonary arterial hypertension include endothelin receptor antagonists such as bosentan, sitaxentan, ambrisentan, macitentan, and oral prostacyclin receptor agonists such as selexipag. Endothelin receptor antagonists have been associated with liver injury, while hepatotoxicity was not reported for selexipag. Although genetic variability has been indisputably associated with variability in drug response, no study has been designed until now to assess its effects on the pharmacokinetics of endothelin receptor antagonists or selexipag.

Case presentation

We report the case of a 58-year-old female Caucasian patient with a dramatic increase in plasma levels of transaminases after treatment with macitentan and selexipag, drugs whose risk of causing liver injury has so far been considered limited. After therapy discontinuation, plasma levels of transaminases returned to baseline, thus suggesting a role of these drugs in the observed hepatotoxicity. After pharmacological counseling, we decided to introduce ambrisentan for the patient’s treatment. After 7 months of treatment, no liver injury has been reported. To evaluate the role of genetic factors in the observed hepatotoxicity, we genotyped the patient for single-nucleotide polymorphisms previously associated with macitentan, ambrisentan, or selexipag metabolism. We found a genetic profile associated with a poor metabolizer (PM) phenotype for CYP2C8 and CYP2C9, key enzymes for elimination of both macitentan and selexipag. The reported results suggest that an allelic profile associated with low activity for CYP2C8 and CYP2C9 enzyme could be a potential risk factor for macitentan and selexipag-induced liver injury and could provide a possible marker for early identification of subjects at higher risk of developing hepatotoxicity.

Conclusions

A multidisciplinary approach based on clinical evaluation, as well as pharmacological counseling and evaluation of the patient’s genetic profile, might be useful for identification of patients with a high chance of drug-induced liver injury, avoiding unnecessary risks in therapy selection and prescription.
SKDStream: a dynamic clustering algorithm on time-decaying data stream
Authors: Liu Hui , Wu Aihua , Wei Mingkang , Chang Chin-Chen
Published: October 2022

Data stream is a type of data that continue to grow over time. For example, network security data stream will constantly be generated in the field of data security, and encrypted data stream will be generated in the privacy protection scenario. Clustering is a basic task in the analysis of data stream. In addition to the large amount of data and limited computer memory, there are the following challenges in time-decaying data stream clustering: (1) How to quickly process time-varying data stream and how to quickly save vaild data. (2) How to maintain and update clusters and track their evolution in real time. Based on the fact that the existing data stream algorithms do not provide a good strategy to the above problems, this paper proposes a dynamic clustering algorithm named SKDStream. The algorithm divides the entire data space into distinct minimal bound hypercubes, which are maintained and indexed by a newly defined structure, SKDTree, that aggregates and updates clusters in real time without requiring large primary storage. Clusters are composed of dense hypercubes. Experiments on synthetic datasets and real datasets show that the response time of the algorithm is similar to that of existing dataflow algorithms, but the quality of the generated clusters is relatively stable over time. Furthermore, the SKDStream algorithm is able to track the evolution of the number of clusters, centers, and density in real time, and compared to D-stream, SKDStream is efficient and effective in clustering.
Diagnostic assessment of novice EFL learners’ discourse competence in academic writing: a case study
Authors: Wang Yumin , Xie Qin
Published: October 2022

Discourse competence is an essential component of communicative competence and central to the mastery of academic writing. This article reports a three-tiered diagnostic assessment of two English as a foreign language (EFL) student writers’ discourse competence in terms of textual features, composing strategies, and knowledge about academic writing. Drawing on extensive analyses of their writing samples, writer logs, and semi-structured interviews, we identified their discourse-level weaknesses and examined their writing strategies and academic writing knowledge status to ascertain their relationships with the observed weaknesses. Global coherence, which conveys the macros-level structure of the whole discourse, was found to be a shared problem of the two students. An investigation into their writing processes found that both students were deadline fighters whose poor time management seemed to account for the problems in their texts. Both spent too much time researching content knowledge but did not reserve sufficient time for writing and revision. Having limited knowledge of the disciplinary content and the required genre type and lacking adequate writing strategies were three salient blocks that impeded their composition of disciplinary essays. Based on the above, we propose a three-stage instructional procedure to facilitate novice EFL learners’ development of discourse competence in English academic writing.
Attitude and perception of pharmacists and healthcare professionals about the criteria used in drug formulary selection in the United Arab Emirates
Authors: Al‑Hemyari Sabaa Saleh , Mohamed Noor Dzul Azri , El‑Dahiyat Faris
Published: October 2022

Background

There is lack of both resources and expertise explains the limited extent to which pharmacoeconomic evidence is used in formulary decision-making.

Objectives

The present study aims to assess attitude and perceptions toward the criteria used to select formulary drugs among UAE healthcare organizations.

Methods

A descriptive cross-sectional study was conducted amongst the licensed physicians in all specialties, all pharmacists and other healthcare professionals with a minimum of 3 month experience those registered with Ministry of health and prevention and those working in the private sector in the UAE. Participants are sent an email containing a validated web-based electronic link to access the questionnaire. The questionnaire composed of two sections is used to assess the healthcare professionals’ attitude and perceptions regarding the criteria used to select formulary drugs. Data analysis were done using SPSS Version 24.

Results

A total of 866 respondents participated in the study and completed the whole questionnaire. The average attitude score about the criteria used in drug formulary selection was 84.5% with a 95% confidence interval (CI) of [83.9%, 85.4%]. Of the total participants, 27 (3.1%) had poor attitude about the criteria used in drug formulary selection, 240 (27.7%) had moderate attitude and 599 (69.2%) had good attitude. The results of statistical modeling showed that education level, area of expertise and age were jointly highly associated with attitude about the criteria used in drug formulary selection.

Conclusions

The study revealed that pharmacists and Healthcare professionals had a good attitude about the criteria used in drug formulary selection in the United Arab Emirates. This study purposed to provide Emirate pharmacy and therapeutics policy makers with a clear criterion of best practice related to methodological recommendations to help in increasing the utilization and implementation of pharmacoeconomic evidence in the drug formulary selection process.
Subinertial frequency variations in the axis of the Tsugaru Warm Current east of the Tsugaru Strait
Authors: Kaneko Hitoshi , Tanaka Takahiro , Abe Hiroto , Wakita Masahide , Sasaki Ken’ichi , Miyazawa Yasumasa , Okunishi Takeshi , Watanabe Shuichi , Tatamisashi Shoko , Sato Yoshiaki
Published: October 2022

The eastern part of the Tsugaru Strait (located at ~ 41.5° N) is a remarkable region of the coastal flow system around Japan due to the Tsugaru Warm Current (TgWC), an intensive eastward current that flows over its complex topography and exhibits marked tidal variation. The TgWC has a jetlike structure and demonstrates drastic seasonal changes in its path and vertical current structure. Using a high-resolution dataset obtained from a high-frequency radar system (HFR) and a coastal data assimilation experiment (JCOPE-T DA), we focused on the frontal variation, which is shorter than the seasonal timescale, along the axis of the TgWC in relation to the meanders of the jet. We found variations in the axis with multiple timescales between 1 and 14 days, especially in summer and autumn. The ~ 14-day variation, a remarkable occurrence on the west side of the eastern Tsugaru Strait, was consistent with the tidal variation in the strait. The zonal scale of the axis meander estimated by the HFR matched a scale several times larger than the internal deformation radius, especially in summer and autumn. JCOPE-T DA outputs showed that the crest of such a meander at greater depths progresses in relation to that at the surface. The outputs also suggested instabilities, indicating potential and kinetic energy conversion from the mean to the eddy field. The propagation speed of the several-day variation in the axis estimated from the HFR data was consistent with that of the two-layer baroclinic instability. The several-day variation also showed relatively high coherence with wind variation from summer to autumn, during which time the seasonal wind over the strait switched from easterly to westerly. These variations with multiple timescales imply an effect on north–south water mass mixing in the eastern part of the strait, including rapid acidification in the strait and intensification of stratification.
Child marriage and health disparities in adulthood: the differential risk of untreated hypertension among young adult women in India
Authors: Datta Biplab Kumar , Haider Mohammad Rifat
Published: October 2022

Background

Hypertension is a major risk factor of cardiovascular diseases, which is the leading cause of premature mortality worldwide. While untreated hypertension heightens the risk of mortality and morbidity among hypertensive individuals, access to hypertension care in low-and-middle income countries has ties with various socioeconomic inequalities. Child brides represent a marginalized group of population who experience various socioeconomic disadvantages. This study investigates whether there exists any disparity in receiving treatment for hypertension between child brides at young adult age and their same-age peers who were married as adults.

Methods

We obtained data on 22,140 currently married hypertensive women aged 20 to 34 years from the 2015–16 wave of National Family Health Survey (NFHS-4) of India. We estimated multilevel univariate and multivariable logistic regressions to obtain the odds in favor of not receiving treatment for hypertension. We compared the odds for child brides with those of their peers who were married as adults.

Results

Among the study participants, 72.6% did not receive any treatment for hypertension. While the share was 70.6% among women who were married as adults, it was 4.3 percentage points higher (P < 0.001) among the child brides. Results from the multilevel logistic regressions reveal that adjusted odds of having untreated hypertension for child brides were 1.12 times (95% confidence interval, 1.00–1.25) that of those who were married as adults.

Conclusions

Our findings show that hypertensive women who were married as children are at greater risk of not receiving hypertension care at young adult age. Therefore, young women who got married in their childhood should be targeted for regular screening and proper referral and treatment to avoid further detrimental effects of elevated blood pressure.
Integrative analyses of genes related to liver ischemia reperfusion injury
Authors: Wang Hang-Pin , Chen Chu-Hong , Wei Ben-Kai , Miao Ying-Lei , Huang Han-Fei , Zeng Zhong
Published: October 2022

Background

Liver ischemia reperfusion injury (LIRI) is not only a common injury during liver transplantation and major hepatic surgery, but also one of the primary factors that affect the outcome of postoperative diseases. However, there are still no reliable ways to tackle the problem. Our study aimed to find some characteristic genes associated with immune infiltration that affect LIRI, which can provide some insights for future research in the future. Therefore, it is essential for the treatment of LIRI, the elucidation of the mechanisms of LIRI, and exploring the potential biomarkers. Efficient microarray and bioinformatics analyses can promote the understanding of the molecular mechanisms of disease occurrence and development.

Method

Data from GSE151648 were downloaded from GEO data sets, and we performed a comprehensive analysis of the differential expression, biological functions and interactions of LIRI-associated genes. Then we performed Gene ontology (GO) analysis and Kyotoencydlopedia of genes and genomes (KEGG) enrichment analysis of DEGs. At last, we performed a protein-protein interaction network to screen out hub genes.

Results

A total of 161 differentially expressed genes (DEGs) were identified. GO analysis results revealed that the changes in the modules were mostly enriched in the neutrophil degranulation, neutrophil activation involved in immune response, and neutrophil mediated immunity. KEGG enrichment analysis of DEGs demonstrated that LIRI mainly involved the cytokine-cytokine receptor interaction. Our data indicated that macrophages and neutrophils are closely related to LIRI. 9 hub genes were screened out in the protein-protein interaction network.

Conclusions

In summary, our data indicated that neutrophil degranulation, neutrophil activation involved in immune response, neutrophil mediated immunity and cytokine-cytokine receptor interaction may play a key role in LIRI, HRH1, LRP2, P2RY6, PKD1L1, SLC8A3 and TNFRSF8, which were identified as potential biomarkers in the occurrence and development of LIRI. However, further studies are needed to validate these findings and explore the molecular mechanism of these biomarkers in LIRI.
The influence of context representations on cognitive control states
Authors: Alzahabi Reem , Hussey Erika , Ward Nathan
Published: October 2022

Cognitive control operates via two distinct mechanisms, proactive and reactive control. These control states are engaged differentially, depending on a number of within-subject factors, but also between-group variables. While research has begun to explore if shifts in control can be experimentally modulated, little is known about whether context impacts which control state is utilized. Thus, we test if contextual factors temporarily bias the use of a particular control state long enough to impact performance on a subsequent task. Our methodology involves two parts: first participants are exposed to a context manipulation designed to promote proactive or reactive processing through amount or availability of advanced preparation within a task-switching paradigm. Then, they complete an AX-CPT task, where we assess immediate transfer on preferential adoption of one control mode over another. We present results from a Pilot Study that revealed anecdotal evidence of proactive versus reactive processing for a context manipulation using long and short preparation times. We also present data from a follow-up Registered Experiment that implements a context manipulation using long or no preparation times to assess if a more extreme context leads to pronounced differences on AX-CPT performance. Together, the results suggest that contextual representations do not impact the engagement of a particular control state, but rather, there is a general preference for the engagement of proactive control.
Elucidation of possible mechanisms of the antidiabetic potential of Zn-loaded Bryophyllum pinnatum (Lam.) extracts in experimental animal models
Authors: Tiwari Varsha , Tiwari Abhishek , Singh Anita , Verma Navneet , Kumar Manish , Sharma Ajay
Published: October 2022

Background

The present study focused on the antidiabetic potential and fingerprinting analysis ofBryophyllumcpinnatumstems as well as its possible mechanisms of action along with identification of its major phytoconstituents. The oral glucose tolerance test has been performed administering a glucose solution (2000 mg/kg) to induce hyperglycemia. Diabetes have been instigated by single intra-peritoneal injection of streptozotocin (65 mg/kg).

Results

Alcohol and aqueous extracts were found to be safe up to a dose of 3000 mg/kg. Oral glucose tolerance test results showed significant reduction in fasting blood glucose level. Alcohol and aqueous extracts (200, 400 mg/kg b.w.) showed significant reduction in fasting blood glucose among all groups. Groups receiving zinc sulfate-loaded extracts showed a statistically significant reduction in low-density lipoproteins, triglycerides and total cholesterol levels and enhanced levels of high density lipoproteins. Fingerprinting analysis has been performed to identify the major phytoconstituents of flavonoid category morin, chrysin, and 6-hydroxy flavones, as well as iso-quercetin, hyperosides and terpenoids present in the extracts possess antidiabetic potential.

Conclusions

Both alcohol and aqueous extracts found to possess significant antidiabetic activity in diabetic rats. Zinc sulfate synergistically potentiates the antidiabetic potential of alcohol extract. Fingerprinting analysis revealed the presence of flavonoids such as morin, chrysin, and 6-hydroxy flavones, as well as iso-quercetin, hyperosides, and terpenoids. The possible mechanisms of antidiabetic activity have been elucidated, although further studies are required to give more elaborated mechanism on molecular basis.

Graphical abstract
Lipopolysaccharide distinctively alters human microglia transcriptomes to resemble microglia from Alzheimer's disease mouse models
Authors: Monzón-Sandoval Jimena , Burlacu Elena , Agarwal Devika , Handel Adam E. , Wei Liting , Davis John , Cowley Sally A. , Cader M. Zameel , Webber Caleb
Published: October 2022

Alzheimer's disease (AD) is the most common form of dementia, and risk-influencing genetics implicates microglia and neuroimmunity in the pathogenesis of AD. Induced pluripotent stem cell (iPSC)-derived microglia (iPSC-microglia) are increasingly used as a model of AD, but the relevance of historical immune stimuli to model AD is unclear. We performed a detailed cross-comparison over time on the effects of combinatory stimulation of iPSC-microglia, and in particular their relevance to AD. We used single-cell RNA sequencing to measure the transcriptional response of iPSC-microglia after 24 h and 48 h of stimulation with prostaglandin E2 (PGE2) or lipopolysaccharide (LPS)+interferon gamma (IFN-γ), either alone or in combination with ATPγS. We observed a shared core transcriptional response of iPSC-microglia to ATPγS and to LPS+IFN-γ, suggestive of a convergent mechanism of action. Across all conditions, we observed a significant overlap, although directional inconsistency to genes that change their expression levels in human microglia from AD patients. Using a data-led approach, we identify a common axis of transcriptomic change across AD genetic mouse models of microglia and show that only LPS provokes a transcriptional response along this axis in mouse microglia and LPS+IFN-γ in human iPSC-microglia.

This article has an associated First Person interview with the first author of the paper.
GM-CSF-activated human dendritic cells promote type 1 T follicular helper cell polarization in a CD40-dependent manner
Authors: Korniotis Sarantis , Saichi Melissa , Trichot Coline , Hoffmann Caroline , Amblard Elise , Viguier Annick , Grondin Sophie , Noel Floriane , Mattoo Hamid , Soumelis Vassili
Published: October 2022

T follicular helper (Tfh) cells regulate humoral responses and present a marked phenotypic and functional diversity. Type 1 Tfh (Tfh1) cells were recently identified and associated with disease severity in infection and autoimmune diseases. The cellular and molecular requirements to induce human Tfh1 differentiation are not known. Here, using single-cell RNA sequencing (scRNAseq) and protein validation, we report that human blood CD1c+ dendritic cells (DCs) activated by GM-CSF (also known as CSF2) drive the differentiation of naive CD4+ T cells into Tfh1 cells. These Tfh1 cells displayed typical Tfh molecular features, including high levels of PD-1 (encoded by PDCD1), CXCR5 and ICOS. They co-expressed BCL6 and TBET (encoded by TBX21), and secreted large amounts of IL-21 and IFN-γ (encoded by IFNG). Mechanistically, GM-CSF triggered the emergence of two DC sub-populations defined by their expression of CD40 and ICOS ligand (ICOS-L), presenting distinct phenotypes, morphologies, transcriptomic signatures and functions. CD40High ICOS-LLow DCs efficiently induced Tfh1 differentiation in a CD40-dependent manner. In patients with mild COVID-19 or latent Mycobacterium tuberculosis infection, Tfh1 cells were positively correlated with a CD40High ICOS-LLow DC signature in scRNAseq of peripheral blood mononuclear cells or blood transcriptomics, respectively. Our study uncovered a novel CD40-dependent Tfh1 axis with potential physiopathological relevance to infection.

This article has an associated First Person interview with the first author of the paper.
Comparison between automated cardiopulmonary resuscitation and manual cardiopulmonary resuscitation in the rescue of cardiac and respiratory arrest
Authors: Niu Huiping , Gao Mengying , Yuan Shuang
Published: October 2022

Objective: To compare the efficacy of automated cardiopulmonary resuscitation (A-CPR) and manual cardiopulmonary resuscitation (M-CPR) in the rescue of cardiac and respiratory arrest.

Methods: A retrospective, single-center observational study was conducted to identify 106 patients by reviewing medical records of 269 patients with cardiac and respiratory arrest treated in The Second Hospital of Hebei Medical University, Shandong Provincial Third Hospital (Jinan, China) from February 2019 to February 2021. Patients were divided into A-CPR group (n = 55) and M-CPR group (n = 51) based on the resuscitation treatment method. The groups were matched for age, gender and the cause of cardiac arrest. Rescue effects, blood gas analysis indicators, respiratory dynamics and condition improvement of the two groups were compared.

Results: In terms of rescue effects, return of spontaneous circulation (ROSC) rate, successful rate of cardiopulmonary resuscitation (CPR), 24-hour survival rate and survival discharge rate in the A-CPR group were higher than M-CPR group (P<0.05). With respect to blood gas analysis indicators and respiratory dynamics, the partial pressure of carbon dioxide (PaCO2) in the A-CPR group was lower than M-CPR group at 15 and 30 minutes after CPR, while the partial pressure of oxygen (PaO2), blood oxygen saturation (SaO2), end expiratory carbon dioxide (PetCO2), coronary perfusion pressure (CPP) and mean arterial pressure (MAP) in the A-CPR group were higher than M-CPR group (P<0.05). In aspect of condition improvement, spontaneous breathing, heart rate, spontaneous circulation, blood pressure recovery time and CPR time in the A-CPR group were shorter than M-CPR group (P<0.05).

Conclusion: The application effect of A-CPR in the rescue of cardiac and respiratory arrest, the improvement of blood gas analysis indexes, respiration and condition improvement are more significant than M-CPR.

doi: https://doi.org/10.12669/pjms.38.8.6598

How to cite this:Gao M, Niu H, Yuan S. Comparison between automated cardiopulmonary resuscitation and manual cardiopulmonary resuscitation in the rescue of cardiac and respiratory arrest. Pak J Med Sci. 2022;38(8):2208-2214. doi: https://doi.org/10.12669/pjms.38.8.6598

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Improving knowledge of Funiculina quadrangularis and vulnerable marine ecosystems in the south Adriatic
Authors: MAČIĆ VESNA , ĐORĐEVIĆ NIKOLA , ĐUROVIĆ MIRKO , PETOVIĆ SLAVICA , RUSSO TOMMASO
Published: October 2022

The Adriatic Sea is one of the most exploited areas in the Mediterranean; however, a large part of the South Adriatic Sea remains largely unexplored. Unfortunately, direct and indirect anthropogenic impacts are increasing exponentially, causing a loss of flagship species and threatening ecosystem functioning. This has led to several international conventions demanding better protection and management of sensitive species and areas worldwide. Soft mud facies bearing the sea pen Funiculina quadrangularis are indicators of vulnerable marine ecosystems (VMEs). This study aimed a) to contribute to the knowledge on the distributions of F. quadrangularis and VMEs, and b) to assess the main threats, thus enabling better identification of areas that need protection and ecosystem base management. The results show that F. quadrangularis are distributed from 160 m to 400 m depth, with the highest population density of 0.83 colony/m2 reported in the Adriatic Sea at a 162 m depth. However, using video ground truthing, we registered stresses on deep-sea habitats originating from fishery and marine litter. Further research is needed to ascertain other potentially vulnerable areas. Moreover, international discussion is needed to determine future steps for the protection and sustainable use of resources beyond national jurisdictions.
Reconsidering the ethics of compulsive treatment in light of clinical psychiatry: A selective review of literature
Authors: Duarte Madeira Luis , Costa Santos Jorge
Published: October 2022

The ethics of compulsive treatment (CT) is a medical, social and legal discussion that reemerged after the ratification by 181 countries of the 2007 United Nations Convention on the Rights of Persons with Disabilities (UN-CRPD). The optional protocol of the UN-CRPD was ratified by 86 countries aiming to promote, protect and ensure the full and equal enjoyment of all human rights. It also determined the need to review mental health laws as under this light treatment of persons with disabilities, particularly those with mental disorders, cannot accept the use of CT. This selective review of literature aims to clarify inputs from clinical psychiatry adding evidence to the multi-disciplinary discussion. It provides contradictory evidence on how patients experience CT and its impact on their mental health and treatment programs, also which are main reasons for the use of CT and what efforts in psychiatry have been made to reduce, replace and refine it.