bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymorphisms in the MBL2 gene are associated with the plasma levels of MBL and the cytokines IL-6 and TNF-α in severe COVID-19
Authors: Queiroz Maria Alice Freitas , Santiago Angélica Menezes , Brito Wandrey Roberto dos Santos , Pereira Keise Adrielle Santos , de Brito William Botelho , Torres Maria Karoliny da Silva , Lopes Jeferson da Costa , Santos Erika Ferreira dos , da Costa Flávia Póvoa , de Sarges Kevin Matheus Lima , Cantanhede Marcos Henrique Damasceno , de Brito Mioni Thieli Figueiredo Magalhães , da Silva Andréa Luciana Soares , Leite Mauro de Meira , Viana Maria de Nazaré do Socorro de Almeida , Rodrigues Fabíola Brasil Barbosa , da Silva Rosilene , Viana Giselle Maria Rachid , Chaves Tânia do Socorro Souza , Veríssimo Adriana de Oliveira Lameira , Carvalho Mayara da Silva , Henriques Daniele Freitas , Santos Carla Pinheiro dos , Nunes Juliana Abreu Lima , Costa Iran Barros , Amoras Ednelza da Silva Graça , Lima Sandra Souza , Cayres-Vallinoto Izaura Maria Vieira , Brasil-Costa Igor , Quaresma Juarez Antônio Simões , Falcão Luiz Fábio Magno , Santos Eduardo José Melo dos , Vallinoto Antonio Carlos Rosário 
Published: April 2023

IntroductionMannose-binding lectin (MBL) promotes opsonization, favoring phagocytosis and activation of the complement system in response to different microorganisms, and may influence the synthesis of inflammatory cytokines. This study investigated the association of MBL2 gene polymorphisms with the plasma levels of MBL and inflammatory cytokines in COVID-19.MethodsBlood samples from 385 individuals (208 with acute COVID-19 and 117 post-COVID-19) were subjected to real-time PCR genotyping. Plasma measurements of MBL and cytokines were performed by enzyme-linked immunosorbent assay and flow cytometry, respectively.ResultsThe frequencies of the polymorphic MBL2 genotype (OO) and allele (O) were higher in patients with severe COVID-19 (p&lt; 0.05). The polymorphic genotypes (AO and OO) were associated with lower MBL levels (p&lt; 0.05). IL-6 and TNF-α were higher in patients with low MBL and severe COVID-19 (p&lt; 0.05). No association of polymorphisms, MBL levels, or cytokine levels with long COVID was observed.DiscussionThe results suggest that, besides MBL2 polymorphisms promoting a reduction in MBL levels and therefore in its function, they may also contribute to the development of a more intense inflammatory process responsible for the severity of COVID-19.
Using quantitative single molecule localization microscopy to optimize multivalent HER2-targeting ligands
Authors: Wakefield Devin L. , Golfetto Ottavia , Jorand Raphael , Biswas Sunetra , Meyer Kassondra , Avery Kendra N. , Zer Cindy , Cacao Eliedonna E. , Tobin Steven J. , Talisman Ian J. , Williams John C. , Jovanovic-Talisman Tijana 
Published: April 2023

IntroductionThe progression-free survival of patients with HER2-positive metastatic breast cancer is significantly extended by a combination of two monoclonal antibodies, trastuzumab and pertuzumab, which target independent epitopes of the extracellular domain of HER2. The improved efficacy of the combination over individual antibody therapies targeting HER2 is still being investigated, and several molecular mechanisms may be in play: the combination downregulates HER2, improves antibody-dependent cell mediated cytotoxicity, and/or affects the organization of surface-expressed antigens, which may attenuate downstream signaling.MethodsBy combining protein engineering and quantitative single molecule localization microscopy (qSMLM), here we both assessed and optimized clustering of HER2 in cultured breast cancer cells.ResultsWe detected marked changes to the cellular membrane organization of HER2 when cells were treated with therapeutic antibodies. When we compared untreated samples to four treatment scenarios, we observed the following HER2 membrane features: (1) the monovalent Fab domain of trastuzumab did not significantly affect HER2 clustering; (2) individual therapy with either trastuzumab or (3) pertuzumab produced significantly higher levels of HER2 clustering; (4) a combination of trastuzumab plus pertuzumab produced the highest level of HER2 clustering. To further enhance this last effect, we created multivalent ligands using meditope technology. Treatment with a tetravalent meditope ligand combined with meditope-enabled trastuzumab resulted in pronounced HER2 clustering. Moreover, compared to pertuzumab plus trastuzumab, at early time points this meditope-based combination was more effective at inhibiting epidermal growth factor (EGF) dependent activation of several downstream protein kinases.DiscussionCollectively, mAbs and multivalent ligands can efficiently alter the organization and activation of the HER2 receptors. We expect this approach could be used in the future to develop new therapeutics.
Evaluation of learning outcomes of humanities curricula in medical students. A meta-review of narrative and systematic reviews
Authors: Coronado-Vázquez Valle , Antón-Rodríguez Cristina , Gómez-Salgado Juan , Ramírez-Durán María del Valle , Álvarez-Montero Santiago 
Published: April 2023

ObjectivesTo assess the expected learning outcomes of medical humanities subjects in medical studies curricula. To connect those expected learning outcomes with the types of knowledge to be acquired in medical education.MethodsMeta-review of systematic and narrative reviews. Cochrane Library, MEDLINE (Pubmed), Embase, CINAHL, and ERIC were searched. In addition, references from all the included studies were revised, and the ISI Web of Science and DARE were searched.ResultsA total of 364 articles were identified, of which six were finally included in the review. Learning outcomes describe the acquisition of knowledge and skills to improve the relationship with patients, as well as the incorporation of tools to reduce burnout and promote professionalism. Programs that focus on teaching humanities promote diagnostic observation skills, the ability to cope with uncertainty in clinical practice, and the development of empathetic behaviors.ConclusionThe results of this review show heterogeneity in the teaching of medical humanities, both in terms of content and at the formal level. Humanities learning outcomes are part of the necessary knowledge for good clinical practice. Consequently, the epistemological approach provides a valid argument for including the humanities in medical curricula.
Risk factors and 180-day mortality of acute kidney disease in critically ill patients: A multi-institutional study
Authors: Pan Heng-Chih , Chen Hsing-Yu , Chen Hui-Ming , Huang Yu-Tung , Fang Ji-Tseng , Chen Yung-Chang 
Published: April 2023

BackgroundCritically ill patients with acute kidney injury (AKI) have a poor prognosis. Recently, the Acute Disease Quality Initiative (ADQI) proposed to define acute kidney disease (AKD) as acute or subacute damage and/or loss of kidney function post AKI. We aimed to identify the risk factors for the occurrence of AKD and to determine the predictive value of AKD for 180-day mortality in critically ill patients.MethodsWe evaluated 11,045 AKI survivors and 5,178 AKD patients without AKI, who were admitted to the intensive care unit between 1 January 2001 and 31 May 2018, from the Chang Gung Research Database in Taiwan. The primary and secondary outcomes were the occurrence of AKD and 180-day mortality.ResultsThe incidence rate of AKD among AKI patients who did not receive dialysis or died within 90 days was 34.4% (3,797 of 11,045 patients). Multivariable logistic regression analysis indicated that AKI severity, underlying early CKD, chronic liver disease, malignancy, and use of emergency hemodialysis were independent risk factors of AKD, while male gender, higher lactate levels, use of ECMO, and admission to surgical ICU were negatively correlated with AKD. 180-day mortality was highest among AKD patients without AKI during hospitalization (4.4%, 227 of 5,178 patients), followed by AKI with AKD (2.3%, 88 of 3,797 patients) and AKI without AKD (1.6%, 115 of 7,133 patients). AKI with AKD had a borderline significantly increased risk of 180-day mortality (aOR 1.34, 95% CI 1.00–1.78; p = 0.047), while patients with AKD but no preceding AKI episodes had the highest risk (aOR 2.25, 95% CI 1.71–2.97; p &lt; 0.001).ConclusionThe occurrence of AKD adds limited additional prognostic information for risk stratification of survivors among critically ill patients with AKI but could predict prognosis in survivors without prior AKI.
Development of a RPA-CRISPR-Cas12a Assay for Rapid, Simple, and Sensitive Detection of Mycoplasma hominis
Authors: Chen Jialing , Huang Yinger , Xiao Bin , Deng Hao , Gong Kunxiang , Li Kun , Li Linhai , Hao Wenbo 
Published: April 2023

Graphical AbstractSchematic of Mycoplasma hominis nucleic acid detection based on the CRISPR-Cas12a system. Clinical samples from cervical or urethral swabs were collected and incubated with lysis buffer to release nucleic acid (10 min). Extracted DNA (1 μl) is subjected to the RPA reaction with specific primers at 37°C. After 20 min, RPA product was subjected to the CRISPR-Cas12a reaction for cleavage. The collateral nuclease activity of Cas12a (250 nM) proteins were activated upon specific binding to crRNA (crRNA3, 62.5 nM) and the DNA product; thus, Cas12a cut the quenched fluorescent ssDNA reporter (125 nM) (30 min). The generated fluorescence signal would be measured by a fluorescence plate reader or visualized by lateral flow strips.
A whole cell-based Matrix-assisted laser desorption/ionization mass spectrometry lipidomic assay for the discovery of compounds that target lipid a modifications
Authors: Tang Wenhao , Osborne Joanne , Dortet Laurent , Larrouy-Maumus Gerald 
Published: April 2023

IntroductionMatrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is a powerful analytical technique that has been applied to a wide variety of applications ranging from proteomics to clinical diagnostics. One such application is its use as a tool for discovery assays, such as monitoring the inhibition of purified proteins. With the global threat from antimicrobial-resistant (AMR) bacteria, new and innovative solutions are required to identify new molecules that could revert bacterial resistance and/or target virulence factors. Here, we used a whole cell-based MALDI-TOF lipidomic assay using a routine MALDI Biotyper Sirius system operating in linear negative ion mode combined with the MBT Lipid Xtract kit to discover molecules targeting bacteria that are resistant to polymyxins, which are considered last-resort antibiotics.MethodsA library of 1200 natural compounds was tested against an E. coli strain expressing mcr-1, which is known to modify lipid A by adding phosphoethanolamine (pETN), making the strain resistant to colistin.Results and DiscussionUsing this approach, we identified 8 compounds that led to a decrease in this lipid A modification by MCR-1 and could potentially be employed to revert resistance. Taken together, as-proof-of-principle, the data we report here represent a new workflow based on the analysis of bacterial lipid A by routine MALDI-TOF for the discovery of inhibitors that could target bacterial viability and/or virulence.
Trimethyl-Chitosan Coated Gold Nanoparticles Enhance Delivery, Cellular Uptake and Gene Silencing Effect of EGFR-siRNA in Breast Cancer Cells
Authors: Baghani Leila , Noroozi Heris Niloofar , Khonsari Fatemeh , Dinarvand Sajad , Dinarvand Meshkat , Atyabi Fatemeh 
Published: April 2023

Purpose: Despite the promising therapeutic effects of gene silencing with small interfering RNAs (siRNAs), the challenges associated with delivery of siRNAs to the tumor cells in vivo, has greatly limited its clinical application. To overcome these challenges, we employed gold nanoparticles modified with trimethyl chitosan (TMC) as an effective delivery carrier to improve the stability and cellular uptake of siRNAs against epidermal growth factor receptor (EGFR) that is implicated in breast cancer.Methods: AuNPs were prepared by the simple aqueous reduction of chloroauric acid (HAuCl4) with ascorbic acid and coated with synthesized TMC. EGFR-siRNA was then complexed with the AuNPs-TMC via electrostatic interaction to make AuNPs-TMC/EGFR-siRNA with a w/w ratio of 10:1. Nanoparticles were assessed for physicochemical characteristics and in vitro cellular behavior on MCF-7 breast cancer cell line.Results: Spherical and positively charged AuNPs-TMC (67 nm, +45 mV) were successfully complexed with EGFR-siRNA (82 nm, +11 mV) which were able to retard the gene migration completely. Confocal microscopy and flow cytometry analysis demonstrated complete cellular uptake of Cy5 labeled AuNPs-TMC in the MCF-7 cells after 4 h incubation. MTT test after 48 h incubation showed that the AuNPs-TMC were safe but when combined with EGFR-siRNA exert significant cytotoxicity while the cell viability was about 50%. These nanocomplexes also showed a high gene expression knockdown (86%) of EGFR and also a high apoptosis rate (Q2 + Q3 = 18.5%) after 24 h incubation.Conclusion: This study suggests that the simply synthesized AuNPs-TMC are novel, effective, and promising nanocarriers for siRNA delivery, and AuNPs-TMC/EGFR-siRNA appears to be a potential therapeutic agent for breast cancer treatment.
(A)symmetry during gait initiation in people with Parkinson’s disease: A motor and cortical activity exploratory study
Authors: Faria Murilo Henrique , Simieli Lucas , Rietdyk Shirley , Penedo Tiago , Santinelli Felipe Balistieri , Barbieri Fabio Augusto 
Published: April 2023

BackgroundGait asymmetry and deficits in gait initiation (GI) are among the most disabling symptoms in people with Parkinson’s disease (PwPD). Understanding if PwPD with reduced asymmetry during GI have higher asymmetry in cortical activity may provide support for an adaptive mechanism to improve GI, particularly in the presence of an obstacle.ObjectiveThis study quantified the asymmetry of anticipatory postural adjustments (APAs), stepping parameters and cortical activity during GI, and tested if the presence of an obstacle regulates asymmetry in PwPD.MethodsSixteen PwPD and 16 control group (CG) performed 20-trials in two conditions: unobstructed and obstructed GI with right and left limbs. We measured, through symmetry index, (i) motor parameters: APAs and stepping, and (ii) cortical activity: the PSD of the frontal, sensorimotor and occipital areas during APA, STEP-I (moment of heel-off of the leading foot in the GI until the heel contact of the same foot); and STEP-II (moment of the heel-off of the trailing foot in the GI until the heel contact of the same foot) phases.ResultsParkinson’s disease showed higher asymmetry in cortical activity during APA, STEP-I and STEP-II phases and step velocity (STEP-II phase) during unobstructed GI than CG. However, unexpectedly, PwPD reduced the level of asymmetry of anterior–posterior displacement (p &lt; 0.01) and medial-lateral velocity (p &lt; 0.05) of the APAs. Also, when an obstacle was in place, PwPD showed higher APAs asymmetry (medial-lateral velocity: p &lt; 0.002), with reduced and increased asymmetry of the cortical activity during APA and STEP-I phases, respectively.ConclusionParkinson’s disease were not motor asymmetric during GI, indicating that higher cortical activity asymmetry can be interpreted as an adaptive behavior to reduce motor asymmetry. In addition, the presence of obstacle did not regulate motor asymmetry during GI in PwPD.
Waist-to-calf circumstance ratio and cognitive function among Chinese older adults: Mediating roles of physical performance and social activity
Authors: Cao Xia , Yang Binfang , Zhou Jiansong 
Published: April 2023

BackgroundIn light of the potentially detrimental effects of central fat and decreased muscle mass on cognitive function, it would be beneficial to learn more about the mediating mechanisms underpinning the association between the two. The purpose of this study is to determine the association between waist-to-calf circumstance ratio (WCR) and cognitive function, as well as to investigate whether physical performance and social activity mediate the relationship between WCR and cognitive function among older Chinese adults.MethodsAn analysis of 9,652 older Chinese adults was conducted during the 2018 wave of the Chinese Longitudinal Health Longevity Survey (CLHLS). The Mini-Mental State Examination (MMSE) and a self-reported scale were used to measure cognitive function, physical performance, and social activity, respectively. Multiple linear regression and mediation analyses were conducted.ResultsThe findings suggest that a high WCR had a significant negative association with cognitive function (B = −0.535, 95% CI: −0.754, −0.317). Mediation analysis revealed that a high WCR influenced old adults' cognitive function in three ways: first, through the partial mediating effect of physical performance (B = −0.270; 95% CI: −0.340, −0.203); second, through the partial mediating effect of social activity (B = −0.035; 95% CI: −0.055, −0.017); and third, through the serial mediating effects of physical performance and social activity (B = −0.021, 95% CI: −0.029, −0.015).ConclusionThe study results suggest the adverse impact of a high WCR on older adults' cognitive function, and the possible mechanisms of physical performance and social activity by which the association takes place. Multidimensional health and social interventions aimed at improving physical, social, and cognitive functioning among older adults with sarcopenic obesity are recommended.
Effect of different modalities of artificial intelligence rehabilitation techniques on patients with upper limb dysfunction after stroke—A network meta-analysis of randomized controlled trials
Authors: Zhu Yu , Wang Chen , Li Jin , Zeng Liqing , Zhang Peizhen 
Published: April 2023

BackgroundThis study aimed to observe the effects of six different types of AI rehabilitation techniques (RR, IR, RT, RT + VR, VR and BCI) on upper limb shoulder-elbow and wrist motor function, overall upper limb function (grip, grasp, pinch and gross motor) and daily living ability in subjects with stroke. Direct and indirect comparisons were drawn to conclude which AI rehabilitation techniques were most effective in improving the above functions.MethodsFrom establishment to 5 September 2022, we systematically searched PubMed, EMBASE, the Cochrane Library, Web of Science, CNKI, VIP and Wanfang. Only randomized controlled trials (RCTs) that met the inclusion criteria were included. The risk of bias in studies was evaluated using the Cochrane Collaborative Risk of Bias Assessment Tool. A cumulative ranking analysis by SUCRA was performed to compare the effectiveness of different AI rehabilitation techniques for patients with stroke and upper limb dysfunction.ResultsWe included 101 publications involving 4,702 subjects. According to the results of the SUCRA curves, RT + VR (SUCRA = 84.8%, 74.1%, 99.6%) was most effective in improving FMA-UE-Distal, FMA-UE-Proximal and ARAT function for subjects with upper limb dysfunction and stroke, respectively. IR (SUCRA = 70.5%) ranked highest in improving FMA-UE-Total with upper limb motor function amongst subjects with stroke. The BCI (SUCRA = 73.6%) also had the most significant advantage in improving their MBI daily living ability.ConclusionsThe network meta-analysis (NMA) results and SUCRA rankings suggest RT + VR appears to have a greater advantage compared with other interventions in improving upper limb motor function amongst subjects with stroke in FMA-UE-Proximal and FMA-UE-Distal and ARAT. Similarly, IR had shown the most significant advantage over other interventions in improving the FMA-UE-Total upper limb motor function score of subjects with stroke. The BCI also had the most significant advantage in improving their MBI daily living ability. Future studies should consider and report on key patient characteristics, such as stroke severity, degree of upper limb impairment, and treatment intensity/frequency and duration.Systematic review registrationwww.crd.york.ac.uk/prospero/#recordDetail, identifier: CRD42022337776.
Cerebral blood flow velocity progressively decreases with increasing levels of verticalization in healthy adults. A cross-sectional study with an observational design
Authors: Deseoe Julian , Schwarz Anne , Pipping Theodor , Lehmann Aurelia , Veerbeek Janne M. , Luft Andreas R. , Wegener Susanne , Globas Christoph , Held Jeremia P. O. 
Published: April 2023

BackgroundAutoregulation of the cerebral vasculature keeps brain perfusion stable over a range of systemic mean arterial pressures to ensure brain functioning, e.g., in different body positions. Verticalization, i.e., transfer from lying (0°) to upright (70°), which causes systemic blood pressure drop, would otherwise dramatically lower cerebral perfusion pressure inducing fainting. Understanding cerebral autoregulation is therefore a prerequisite to safe mobilization of patients in therapy.AimWe measured the impact of verticalization on cerebral blood flow velocity (CBFV) and systemic blood pressure (BP), heart rate (HR) and oxygen saturation in healthy individuals.MethodsWe measured CBFV in the middle cerebral artery (MCA) of the dominant hemisphere in 20 subjects using continuous transcranial doppler ultrasound (TCD). Subjects were verticalized at 0°, −5°, 15°, 30°, 45° and 70° for 3–5 min each, using a standardized Sara Combilizer chair. In addition, blood pressure, heart rate and oxygen saturation were continuously monitored.ResultsWe show that CBFV progressively decreases in the MCA with increasing degrees of verticalization. Systolic and diastolic BP, as well as HR, show a compensatory increase during verticalization.ConclusionIn healthy adults CBFV changes rapidly with changing levels of verticalization. The changes in the circulatory parameters are similar to results regarding classic orthostasis.RegistrationClinicalTrials.gov, identifier: NCT04573114.
The prevalence and risk factors of anxiety in multiple sclerosis: A systematic review and meta-analysis
Authors: Zhang Xiaoyun , Song Ying , Wei Zhiqiang , Chen Xiao , Zhuang Xiaojia , Yi Li 
Published: April 2023

BackgroundPatients with multiple sclerosis (MS) suffer from repetitive neurological deterioration, while anxiety may play a significant role in the disease’s progression.ObjectiveTo explore the prevalence of anxiety in MS and to investigate the risk factors related to anxiety in MS patients.MethodsAn analysis of four databases, PubMed, Web of Science, EMBASE, and Cochrane Library, has been conducted to determine the prevalence or risk factors for anxiety in MS published before May 2021.ResultsIn total, 32 studies were found to be eligible. Anxiety prevalence was estimated to be 36% based on the pooled estimates [the 95% confidence interval (CI) = [0.30–0.42],I2= 98.4%]. Significant risk factors for developing of anxiety were as follows: age at survey [the weighted mean difference (WMD) = 0.96, 95% CI = [0.86–1.06],I2= 43.8%], female [the odd ratio (OR) = 1.78, 95% CI = [1.38–2.30],I2= 0%], living together (OR 2.83, 95% CI = [1.74–4.59],I2= 0%), past psychiatric history (OR 2.42, 95% CI = [1.56–3.75],I2= 0%), depression (OR 7.89, 95% CI = [3.71–16.81],I2= 0%), not taking MS medication (OR 2.33, 95% CI = [1.29–4.21],I2= 77.8%), relapsing-remitting MS (RRMS) (OR 1.50, 95% CI = [0.94–2.37],I2= 53.5%), and baseline Expanded Disability Status Scale (EDSS) (OR 0.84, 95% CI = [0.48–1.21],I2= 62.2%).ConclusionAn estimated 36% of people with MS suffer from anxiety. And anxiety rates in MS patients are significantly associated with age, gender, living together, prior psychiatric history, depression, drug compliance, RRMS, and baseline EDSS.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=287069, identifier CRD42021287069.