bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting omicron pneumonia severity and outcome: a single-center study in Hangzhou, China
Authors: Xu Jingjing , Cao Zhengye , Miao Chunqin , Zhang Minming , Xu Xiaojun 
Published: May 2023

BackgroundIn December 2022, there was a large Omicron epidemic in Hangzhou, China. Many people were diagnosed with Omicron pneumonia with variable symptom severity and outcome. Computed tomography (CT) imaging has been proven to be an important tool for COVID-19 pneumonia screening and quantification. We hypothesized that CT-based machine learning algorithms can predict disease severity and outcome in Omicron pneumonia, and we compared its performance with the pneumonia severity index (PSI)-related clinical and biological features.MethodsOur study included 238 patients with the Omicron variant who have been admitted to our hospital in China from 15 December 2022 to 16 January 2023 (the first wave after the dynamic zero-COVID strategy stopped). All patients had a positive real-time polymerase chain reaction (PCR) or lateral flow antigen test for SARS-CoV-2 after vaccination and no previous SARS-CoV-2 infections. We recorded patient baseline information pertaining to demographics, comorbid conditions, vital signs, and available laboratory data. All CT images were processed with a commercial artificial intelligence (AI) algorithm to obtain the volume and percentage of consolidation and infiltration related to Omicron pneumonia. The support vector machine (SVM) model was used to predict the disease severity and outcome.ResultsThe receiver operating characteristic (ROC) area under the curve (AUC) of the machine learning classifier using PSI-related features was 0.85 (accuracy = 87.40%, p &lt; 0.001) for predicting severity while that using CT-based features was only 0.70 (accuracy = 76.47%, p = 0.014). If combined, the AUC was not increased, showing 0.84 (accuracy = 84.03%, p &lt; 0.001). Trained on outcome prediction, the classifier reached the AUC of 0.85 using PSI-related features (accuracy = 85.29%, p &lt; 0.001), which was higher than using CT-based features (AUC = 0.67, accuracy = 75.21%, p &lt; 0.001). If combined, the integrated model showed a slightly higher AUC of 0.86 (accuracy = 86.13%, p &lt; 0.001). Oxygen saturation, IL-6, and CT infiltration showed great importance in both predicting severity and outcome.ConclusionOur study provided a comprehensive analysis and comparison between baseline chest CT and clinical assessment in disease severity and outcome prediction in Omicron pneumonia. The predictive model accurately predicts the severity and outcome of Omicron infection. Oxygen saturation, IL-6, and infiltration in chest CT were found to be important biomarkers. This approach has the potential to provide frontline physicians with an objective tool to manage Omicron patients more effectively in time-sensitive, stressful, and potentially resource-constrained environments.
Dysfunction of inhibitory interneurons contributes to synaptic plasticity via GABABR-pNR2B signaling in a chronic migraine rat model
Authors: Zeng Xiaoxu , Niu Yingying , Qin Guangcheng , Zhang Dunke , Chen Lixue 
Published: May 2023

BackgroundAccording to our previous study, the loss of inhibitory interneuron function contributes to central sensitization in chronic migraine (CM). Synaptic plasticity is a vital basis for the occurrence of central sensitization. However, whether the decline in interneuron-mediated inhibition promotes central sensitization by regulating synaptic plasticity in CM remains unclear. Therefore, this study aims to explore the role of interneuron-mediated inhibition in the development of synaptic plasticity in CM.MethodsA CM model was established in rats by repeated dural infusion of inflammatory soup (IS) for 7 days, and the function of inhibitory interneurons was then evaluated. After intraventricular injection of baclofen [a gamma-aminobutyric acid type B receptor (GABABR) agonist] or H89 [a protein kinase A (PKA) inhibitor), behavioral tests were performed. The changes in synaptic plasticity were investigated by determining the levels of the synapse-associated proteins postsynaptic density protein 95 (PSD95), synaptophysin (Syp) and synaptophysin-1(Syt-1)]; evaluating the synaptic ultrastructure by transmission electron microscopy (TEM); and determining the density of synaptic spines via Golgi-Cox staining. Central sensitization was evaluated by measuring calcitonin gene-related peptide (CGRP), brain-derived neurotrophic factor (BDNF), c-Fos and substance P (SP) levels. Finally, the PKA/Fyn kinase (Fyn)/tyrosine-phosphorylated NR2B (pNR2B) pathway and downstream calcium-calmodulin-dependent kinase II (CaMKII)/c-AMP-responsive element binding protein (pCREB) signaling were assessed.ResultsWe observed dysfunction of inhibitory interneurons, and found that activation of GABABR ameliorated CM-induced hyperalgesia, repressed the CM-evoked elevation of synapse-associated protein levels and enhancement of synaptic transmission, alleviated the CM-triggered increases in the levels of central sensitization-related proteins, and inhibited CaMKII/pCREB signaling via the PKA/Fyn/pNR2B pathway. The inhibition of PKA suppressed the CM-induced activation of Fyn/pNR2B signaling.ConclusionThese data reveal that the dysfunction of inhibitory interneurons contributes to central sensitization by regulating synaptic plasticity through the GABABR/PKA/Fyn/pNR2B pathway in the periaqueductal gray (PAG) of CM rats. Blockade of GABABR-pNR2B signaling might have a positive influence on the effects of CM therapy by modulating synaptic plasticity in central sensitization.
Maternal preconception BMI and gestational weight gain are associated with weight retention and maternal and child body fat at 6–7 years postpartum in the PRECONCEPT cohort
Authors: Young Melissa F. , Nguyen Phuong Hong , Tran Lan Mai , Khuong Long Quynh , Hendrix Sara , Martorell Reynaldo , Ramakrishnan Usha 
Published: May 2023

BackgroundThere is limited evidence from prospective cohorts in low-resource settings on the long-term impact of pre-pregnancy body mass index (PPBMI) and gestational weight gain (GWG) on postpartum weight retention (PPWR) and maternal and child body composition.ObjectivesWe examined the associations between PPBMI and timing of GWG on PPWR at 1, 2, and 6–7 years and maternal and child percent body fat at 6–7 years.MethodsWe used data from the PRECONCEPT study (NCT01665378) that included prospectively collected data on 864 mother–child pairs from preconception through 6–7 years postpartum. The key outcomes were PPWR at 1, 2, and 6–7 years, and maternal and child percent body fat at 6–7 years that was measured using bioelectric impedance. Maternal conditional GWG (CGWG) was defined as window-specific weight gains (&lt; 20wk, 21-29wk, and  ≥ 30wk), uncorrelated with PPBMI and all prior body weights. PPBMI and CGWG were calculated as standardized z-scores to allow for relative comparisons of a 1 standard deviation (SD) increase in weight gain for each window. We used multivariable linear regressions to examine the associations, adjusting for baseline demographic characteristics, intervention, breastfeeding practices, diet and physical activity.ResultsMean (SD) PPBMI and GWG were 19.7 (2.1) kg/m2 and 10.2 (4.0) kg, respectively. Average PPWR at 1, 2, and 6–7 years was 1.1, 1.5 and 4.3 kg, respectively. A one SD increase in PPBMI was associated with a decrease in PPWR at 1 year (β [95% CI]: −0.21 [−0.37, −0.04]) and 2 years (−0.20 [−0.39, −0.01]); while a one SD in total CGWG was associated with an increase in PPWR at 1 year (1.01 [0.85,1.18]), 2 years (0.95 [0.76, 1.15]) and 6–7 years (1.05 [0.76, 1.34]). Early CGWG (&lt; 20 weeks) had the greatest association with PPWR at each time point as well as with maternal (0.67 [0.07, 0.87]) and child (0.42 [0.15, 0.69]) percent body fat at 6–7 years.ConclusionMaternal nutrition before and during pregnancy may have long-term implications for PPWR and body composition. Interventions should consider targeting women preconception and early in pregnancy to optimize maternal and child health outcomes.
Spinal cord vascular degeneration impairs duloxetine penetration
Authors: Da Vitoria Lobo M. E , Madden R , Liddell S , Hirashima M , Hulse R. P 
Published: May 2023

IntroductionChronic pain is a prevalent physically debilitating health-related morbidity. Frontline analgesics are inadequate, providing only partial pain relief in only a proportion of the patient cohort. Here, we explore whether alterations in spinal cord vascular perfusion are a factor in reducing the analgesic capability of the noradrenaline reuptake inhibitor, duloxetine.MethodAn established rodent model of spinal cord vascular degeneration was used. Endothelial-specific vascular endothelial growth factor receptor 2 knockout mouse was induced via hydroxytamoxifen administered via intrathecal injection. Duloxetine was administered via intraperitoneal injection, and nociceptive behavioural testing was performed in both WT and VEGFR2KO mice. LC-MS/MS was performed to explore the accumulation of duloxetine in the spinal cord in WT and VEGFR2KO mice.ResultsSpinal cord vascular degeneration leads to heat hypersensitivity and a decline in capillary perfusion. The integrity of noradrenergic projections (dopa - hydroxylase labelled) in the dorsal horn remained unaltered in WT and VEGFR2KO mice. There was an association between dorsal horn blood flow with the abundance of accumulated duloxetine in the spinal cord and analgesic capacity. In VEGFR2KO mice, the abundance of duloxetine in the lumbar spinal cord was reduced and was correlated with reduced anti-nociceptive capability of duloxetine.DiscussionHere, we show that an impaired vascular network in the spinal cord impairs the anti-nociceptive action of duloxetine. This highlights that the spinal cord vascular network is crucial to maintaining the efficacy of analgesics to provide pain relief.
Development of a population pharmacokinetic model of pyrazinamide to guide personalized therapy: impacts of geriatric and diabetes mellitus on clearance
Authors: Kim Ryunha , Jayanti Rannissa Puspita , Lee Hongyeul , Kim Hyun-Kuk , Kang Jiyeon , Park I-Nae , Kim Jehun , Oh Jee Youn , Kim Hyung Woo , Lee Heayon , Ghim Jong-Lyul , Ahn Sangzin , Long Nguyen Phuoc , Cho Yong-Soon , Shin Jae-Gook , On behalf of the cPMTb  
Published: May 2023

Objectives: This study was performed to develop a population pharmacokinetic model of pyrazinamide for Korean tuberculosis (TB) patients and to explore and identify the influence of demographic and clinical factors, especially geriatric diabetes mellitus (DM), on the pharmacokinetics (PK) of pyrazinamide (PZA).Methods: PZA concentrations at random post-dose points, demographic characteristics, and clinical information were collected in a multicenter prospective TB cohort study from 18 hospitals in Korea. Data obtained from 610 TB patients were divided into training and test datasets at a 4:1 ratio. A population PK model was developed using a nonlinear mixed-effects method.Results: A one-compartment model with allometric scaling for body size effect adequately described the PK of PZA. Geriatric patients with DM (age &gt;70 years) were identified as a significant covariate, increasing the apparent clearance of PZA by 30% (geriatric patients with DM: 5.73 L/h; others: 4.50 L/h), thereby decreasing the area under the concentration–time curve from 0 to 24 h by a similar degree compared with other patients (geriatric patients with DM: 99.87 μg h/mL; others: 132.3 μg h/mL). Our model was externally evaluated using the test set and provided better predictive performance compared with the previously published model.Conclusion: The established population PK model sufficiently described the PK of PZA in Korean TB patients. Our model will be useful in therapeutic drug monitoring to provide dose optimization of PZA, particularly for geriatric patients with DM and TB.
Essential role of microglia in the fast antidepressant action of ketamine and hypidone hydrochloride (YL-0919)
Authors: Chang Hai-Xia , Dai Wei , Bao Jin-Hao , Li Jin-Feng , Zhang Ji-Guo , Li Yun-Feng 
Published: May 2023

Introduction: Intracerebral microglia play a vital role in mediating central immune response, neuronal repair and synaptic pruning, but its precise role and mechanism in fast action of antidepressants have remained unknown. In this study, we identified that the microglia contributed to the rapid action of antidepressants ketamine and YL-0919.Methods: The depletion of microglia was achieved with the diet containing the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 in mice. The tail suspension test (TST), forced swimming test (FST) and novelty suppressed feeding test (NSFT) were employed to evaluate the rapid acting antidepressant behavior of ketamine and YL-0919 in the microglia depletion model. The number of microglia in the prefrontal cortex (PFC) was assayed by the immunofluorescence staining. The expressions of synaptic proteins (synapsin-1, PSD-95, GluA1) and brain-derived neurotrophic factor (BDNF) in the PFC were tested by Western blot.Results: The immobility duration in FST and the latency to feed in NSFT were shortened 24 h after an intraperitoneal (i.p.) injection of ketamine (10 mg/kg). The microglial depletion of PLX3397 blocked the rapid antidepressant-like effect of ketamine in mice. In addition, the immobility time in TST and FST as well as latency to feed in NSFT were reduced 24 h after the intragastric (i.g.) administration of YL-0919 (2.5 mg/kg, administered for 5–6 consecutive days), and the rapid antidepressant effect of YL-0919 was also blocked by the microglial depletion using PLX5622. About 92% of microglia in the prefrontal cortex was depleted in PLX5622 diet-fed mice, while both ketamine and YL-0919 promoted proliferation on the remaining microglia. YL-0919 significantly increased the protein expressions of synapsin-1, PSD-95, GluA1 and BDNF in the PFC, all of which could be blocked by PLX5622.Conclusion: These results suggested the microglia underlying the rapid antidepressant-like effect of ketamine and YL-0919, and microglia would likely constitute in the rapid enhancing impact of synaptic plasticity in the prefrontal cortex by YL-0919.
Association of oral bisphosphonates with cardioembolic ischemic stroke: a nested case-control study
Authors: Rodríguez-Martín Sara , Barreira-Hernández Diana , Mazzucchelli Ramón , Gil Miguel , García-Lledó Alberto , Izquierdo-Esteban Laura , Pérez-Gómez Ana , Rodríguez-Miguel Antonio , De Abajo Francisco J. 
Published: May 2023

Background: Bisphosphonates have been reported to increase the risk of atrial fibrillation. Therefore, it is conceivable that they may increase the risk of cardioembolic ischemic stroke (IS). However, most epidemiological studies carried out thus far have not shown an increased risk of IS, though none separated by the main pathophysiologic IS subtype (cardioembolic and non-cardioembolic) which may be crucial. In this study, we tested the hypothesis that the use of oral bisphosphonates increases specifically the risk of cardioembolic IS, and explored the effect of treatment duration, as well as the potential interaction between oral bisphosphonates and calcium supplements and anticoagulants.Methods: We performed a case-control study nested in a cohort of patients aged 40–99 years, using the Spanish primary healthcare database BIFAP, over the period 2002-2015. Incident cases of IS were identified and classified as cardioembolic or non-cardioembolic. Five controls per case were randomly selected, matched for age, sex, and index date (first recording of IS) using an incidence-density sampling. The association of IS (overall and by subtype) with the use of oral bisphosphonates within the last year before index date was assessed by computing the adjusted odds ratios (AOR) and their 95% CI using a conditional logistic regression. Only initiators of oral bisphosphonates were considered.Results: A total of 13,781 incident cases of IS and 65,909 controls were included. The mean age was 74.5 (SD ± 12.4) years and 51.6% were male. Among cases, 3.15% were current users of oral bisphosphonates, while among controls they were 2.62%, yielding an AOR of 1.15 (95% CI:1.01–1.30). Of all cases, 4,568 (33.1%) were classified as cardioembolic IS (matched with 21,697 controls) and 9,213 (66.9%) as non-cardioembolic IS (matched with 44,212 controls) yielding an AOR of 1.35 (95% CI:1.10–1.66) and 1.03 (95% CI: 0.88–1.21), respectively. The association with cardioembolic IS was clearly duration-dependent (AOR≤1 year = 1.10; 95% CI:0.82–1.49; AOR&gt;1–3 years = 1.41; 95% CI:1.01–1.97; AOR&gt;3 years = 1.81; 95% CI:1.25–2.62; p for trend = 0.001) and completely blunted by anticoagulants, even in long-term users (AOR&gt;1 year = 0.59; 0.30–1.16). An interaction between oral bisphosphonates and calcium supplements was suggested.Conclusion: The use of oral bisphosphonates increases specifically the odds of cardioembolic IS, in a duration-dependent manner, while leaves materially unaffected the odds of non-cardioembolic IS.
Synthesis, structure-activity relationships and biological evaluation of benzimidazole derived sulfonylurea analogues as a new class of antagonists of P2Y1 receptor
Authors: Bano Sehrish , Hussain Zahid , Langer Peter , Weisman Gary A. , Iqbal Jamshed 
Published: May 2023

The P2Y receptors are responsible for the regulation of various physiological processes including neurotransmission and inflammatory responses. These receptors are also considered as novel potential therapeutic targets for prevention and treatment of thrombosis, neurological disorders, pain, cardiac diseases and cancer. Previously, number of P2Y receptor antagonists has been investigated but they are less potent and non-selective with poor solubility profile. Herein, we present the synthesis of new class of benzimidazole derived sulfonylureas (1a-y) as potent antagonists of P2Y receptors, with the specific aim to explore selective antagonists of P2Y1 receptors. The efficacy and selectivity of the synthesized derivatives 1) against four P2Y receptors i.e., t-P2Y1, h-P2Y2, h-P2Y4, and r-P2Y6Rs was carried out by calcium mobilization assay. The results revealed that except 1b, 1d, 1l, 1m, 1o, 1u, 1v, 1w, and 1y, rest of the synthesized derivatives exhibited moderate to excellent inhibitory potential against P2Y1 receptors. Among the potent antagonists, derivative 1h depicted the maximum inhibition of P2Y1 receptor in calcium signalling assay, with an IC50 value of 0.19 ± 0.04 µM. The potential of inhibition was validated by computational investigations where bonding and non-bonding interactions between ligand and targeted receptor further strengthen the study. The best identified derivative 1h revealed the same binding mechanism as that of already reported selective antagonist of P2Y1 receptor i.e (1-(2- (2-tert-butyl-phenoxy) pyridin-3-yl)-3–4-(trifluoromethoxy) phenylurea but the newly synthesized derivative exhibited better solubility profile. Hence, this derivative can be used as lead candidate for the synthesis of more potential antagonist with much better solubility profile and medicinal importance.
Exploring the relationship of static and dynamic balance with muscle mechanical properties of the lower limbs in healthy young adults
Authors: Hill Mathew W. , Wdowski Maximilian M. , Rosicka Katarzyna , Kay Anthony D. , Muehlbauer Thomas 
Published: May 2023

There is emerging evidence that mechanical properties of in vivo muscle tissues are associated with postural sway during quiet standing. However, it is unknown if the observed relationship between mechanical properties with static balance parameters generalise to dynamic balance. Thus, we determined the relationship between static and dynamic balance parameters with muscle mechanical properties of the ankle plantar flexors [lateral gastrocnemius (GL)] and knee extensors [vastus lateralis (VL)] in vivo. Twenty-six participants (men = 16, women = 10; age = 23.3 ± 4.4 years) were assessed for static balance [centre of pressure (COP) movements during quiet standing], dynamic balance (reach distances for the Y-balance test) and mechanical properties (stiffness and tone) of the GL and VL measured in the standing and lying position. Significant (p &lt; .05) small to moderate inverse correlations were observed between the mean COP velocity during quiet standing with stiffness (r = −.40 to −.58, p = .002 to .042) and tone (r = −0.42 to −0.56, p = 0.003 to 0.036) of the GL and VL (lying and standing). Tone and stiffness explained 16%–33% of the variance in the mean COP velocity. Stiffness and tone of the VL measured in the lying (supine) condition were also inversely significantly correlated with Y balance test performance (r = −0.39 to −0.46, p = 0.018 to 0.049). These findings highlight that individuals with low muscle stiffness and tone exhibit faster COP movements during quiet standing, indicative of reduced postural control but also reveal that low VL stiffness and tone are associated with greater reach distances in a lower extremity reaching task, indicative of greater neuromuscular performance.
Supportive care needs and health-related quality of life in cancer patients receiving palliative care
Authors: Schnabel Astrid , Lordick Florian , Oberth Paula , Neuschulz Markus , Lehmann-Laue Antje , Mehnert-Theuerkauf Anja , Hinz Andreas 
Published: May 2023

ObjectiveCancer patients receiving palliative care experience a variety of impairments in their quality of life (QoL), and have corresponding supportive care needs (SCNs). The aim of this study was to analyze the relationship between SCNs, satisfaction with QoL dimensions, and the perceived importance of these dimensions.MethodA sample of 152 cancer patients receiving palliative care were included in this cross-sectional study. Eight dimensions of QoL were defined and assessed concerning SCNs, satisfaction, and subjective importance using a new assessment instrument with five-point scales (range 1–5) for each dimension.ResultsAmong the eight specific domains examined, the greatest SCNs were observed for absence of pain (M = 3.18; SD = 1.29). The patients were least satisfied with their physical functioning (M = 2.60; SD = 0.84), and the dimension social relationships (M = 4.14; SD = 0.72) received the highest perceived importance ratings. The eight dimensions’ SCNs scores were significantly correlated with each other (r between 0.29 and 0.79); the lowest correlations were found for social relationships. The correlations between the satisfaction scores and the SCNs differed from dimension to dimension, with coefficients between −0.32 (absence of pain) and − 0.57 (sleep quality).ConclusionThe results show that detriments in QoL do not automatically indicate high levels of SCNs in those dimensions. Health care providers should consider both factors, QoL (as measured with QoL questionnaires) and subjectively expressed SCNs, to optimize their patients’ care regimens.