bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of bacterial hosts for conversion of lignin-derived p-coumaric acid to 4-vinylphenol
Authors: Rodriguez Alberto , Meadows Jamie A. , Sun Ning , Simmons Blake A. , Gladden John M. 
Published: September 2021

AbstractHydroxycinnamic acids such as p-coumaric acid (CA) are chemically linked to lignin in grassy biomass with fairly labile ester bonds and therefore represent a straightforward opportunity to extract and valorize lignin components. In this work, we investigated the enzymatic conversion of CA extracted from lignocellulose to 4-vinylphenol (4VP) by expressing a microbial phenolic acid decarboxylase in Corynebacterium glutamicum, Escherichia coli, and Bacillus subtilis. The performance of the recombinant strains was evaluated in response to the substrate concentration in rich medium or a lignin liquor and the addition of an organic overlay to perform a continuous product extraction in batch cultures. We found that using undecanol as an overlay enhanced the 4VP titers under high substrate concentrations, while extracting > 97% of the product from the aqueous phase. C. glutamicum showed the highest tolerance to CA and resulted in the accumulation of up to 187 g/L of 4VP from pure CA in the overlay with a 90% yield when using rich media, or 17 g/L of 4VP with a 73% yield from CA extracted from lignin. These results indicate that C. glutamicum is a suitable host for the high-level production of 4VP and that further bioprocess engineering strategies should be explored to optimize the production, extraction, and purification of 4VP from lignin with this organism.
Environmental asbestos exposure and clustering of malignant mesothelioma in community: a spatial analysis in a population-based case–control study
Authors: Airoldi C. , Magnani C. , Lazzarato F. , Mirabelli D. , Tunesi S. , Ferrante D. 
Published: September 2021

AbstractBackgroundNeighborhood exposure to asbestos increases the risk of developing malignant mesothelioma (MM) in residents who live near asbestos mines and asbestos product plants. The area of Casale Monferrato (Northwest Italy) was impacted by several sources of asbestos environmental pollution, due to the presence of the largest Italian asbestos cement (AC) plant. In the present study, we examined the spatial variation of MM risk in an area with high levels of asbestos pollution and secondly, and we explored the pattern of clustering.MethodsA population-based case–control study conducted between 2001 and 2006 included 200 cases and 348 controls. Demographic and occupational data along with residential information were recorded. Bivariate Kernel density estimation was used to map spatial variation in disease risk while an adjusted logistic model was applied to estimate the impact of residential distance from the AC plant. Kulldorf test and Cuzick Edward test were then performed.ResultsOne hundred ninety-six cases and 322 controls were included in the analyses. The contour plot of the cases to controls ratio showed a well-defined peak of MM incidence near the AC factory, and the risk decreased monotonically in all directions when large bandwidths were used. However, considering narrower smoothing parameters, several peaks of increased risk were reported. A constant trend of decreasing OR with increasing distance was observed, with estimates of 10.9 (95% CI 5.32–22.38) and 10.48 (95%CI 4.54–24.2) for 0–5 km and 5–10 km, respectively (reference > 15 km). Finally, a significant (p < 0.0001) excess of cases near the pollution source was identified and cases are spatially clustered relative to the controls until 13 nearest neighbors.ConclusionsIn this study, we found an increasing pattern of mesothelioma risk in the area around a big AC factory and we detected secondary clusters of cases due to local exposure points, possibly associated to the use of asbestos materials.
Platelet factor 4 polyanion immune complexes: heparin induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia
Authors: Datta Payel , Zhang Fuming , Dordick Jonathan S. , Linhardt Robert J. 
Published: September 2021

Abstract
Background
This is a review article on heparin-induced thrombocytopenia, an adverse effect of heparin therapy, and vaccine-induced immune thrombotic thrombocytopenia, occurring in some patients administered certain coronavirus vaccines.

Main body/text
Immune-mediated thrombocytopenia occurs when specific antibodies bind to platelet factor 4 /heparin complexes. Platelet factor 4 is a naturally occurring chemokine, and under certain conditions, may complex with negatively charged molecules and polyanions, including heparin. The antibody-platelet factor 4/heparin complex may lead to platelet activation, accompanied by other cascading reactions, resulting in cerebral sinus thrombosis, deep vein thrombosis, lower limb arterial thrombosis, myocardial infarction, pulmonary embolism, skin necrosis, and thrombotic stroke. If untreated, heparin-induced thrombocytopenia can be life threatening. In parallel, rare incidents of spontaneous vaccine-induced immune thrombotic thrombocytopenia can also occur in some patients administered certain coronavirus vaccines. The role of platelet factor 4 in vaccine-induced thrombosis with thrombocytopenia syndrome further reinforces the importance the platelet factor 4/polyanion immune complexes and the complications that this might pose to susceptible individuals. These findings demonstrate, how auxiliary factors can complicate heparin therapy and drug development. An increasing interest in biomanufacturing heparins from non-animal sources has driven a growing interest in understanding the biology of immune-mediated heparin-induced thrombocytopenia, and therefore, the development of safe and effective biosynthetic heparins.

Short conclusion
In conclusion, these findings further reinforce the importance of the binding of platelet factor 4 with known and unknown polyanions, and the complications that these might pose to susceptible patients. In parallel, these findings also demonstrate how auxiliary factors can complicate the heparin drug development.
Awareness of obstetric fistula and associated factors among women in reproductive age group attending public hospitals in southwest Ethiopia, 2021
Authors: Rundasa Dessalegn Nigatu , Wolde Tarekegn Fekede , Ayana Kenbon Bayisa , Worke Abeya Fufa 
Published: September 2021

Abstract
Background
Obstetric fistula occurs in all developing countries but it is confined to the “fistula belt” across the northern half of Sub-Saharan Africa from Mauritania to Eritrea and in the developing countries of the Middle East and Asia. Ending obstetric fistula is critical to achieving Sustainable Development by 2030. So creating awareness on obstetrics fistula among women in the reproductive age group have a crucial role in reducing morbidity, mortality, and social stigma.

Objective
To assess awareness on obstetric fistula and its associated factors among reproductive-age women attending governmental hospitals in southwest Ethiopia, 2021.

Methods
An Institutional based cross-sectional study design was conducted among 413 women. The sample size was estimated by using a single population proportion formula. The collected data were coded and entered into EPI-data version 3.1 then exported to SPSS version 24 for descriptive and inferential analysis. Adjusted odds ratio (AOR) along with 95% confidence level was estimated to assess the strength of the association and variables with a p-value < 0.05 were considered to declare the statistical significance in the multivariable analysis in this study.

Results
In this study, a total of 400 clients have participated in the study. The mean ages of participants were 30.26 (SD ± 8.525) years old. Education of women who cannot read and write are 85% less likely to have good awareness than women who are above the secondary level of education [AOR = 0.162; 95% CI (0.081–0.364)]. While Women who have primary education level are 83% less likely to have good awareness than women who are above the secondary level of education [AOR = 0.170; 95% CI (0.085–0.446)]. In addition, This study shows women who have not heard about obstetric complications are 54% less likely to have awareness of obstetric fistula than those who heard about obstetric complications [AOR = 0.458; 95% CI (0.368–0.643)].

Conclusion
This study identifies that the educational level of women, history of pregnancy, distance to the nearby health institution, and awareness of obstetrics complications were the factors associated with awareness of reproductive age women on obstetrics fistula. Hence, increasing awareness on obstetric fistula plays a key role in averting this problem.
Does clozapine really affect bone mineral density? An experimental study
Authors: Aydin Bahattin Kerem , Safali Selim , Aydin Memduha , Egilmez Umran , Cebeci Hakan , Çelik Murat , Abdulrezzak Ummuhan 
Published: September 2021

Abstract
Purpose
The aim of this study was to investigate the effect of clozapine use on bone tissue by applying computerized tomography, dual-energy X-ray absorptiometry, and histological and biomechanical analyses in an experimental rat model.

Methods
Sixteen female Wistar Albino rats were included in this study. These animals were divided into two groups: the control group and the clozapine group. The animals in the clozapine group received 10 mg/kg clozapine, and the animals in the control group received tap water by oral gavage daily for 28 days. After sacrification, the femurs of the rats were used for radiologic, histologic, dual-energy X-ray absorptiometry, and biomechanical evaluations.

Results
Although the mean values of the clozapine group were higher in terms of histological, bone mineral density, and biomechanical evaluations, the statistical analyses were not significantly different.

Conclusion
Clozapine use did not affect bone density in the rats. Clozapine can be the preferred treatment for patients with schizophrenia to avoid osteoporosis. It will be necessary to conduct further long-term follow-up and controlled studies in animals and humans to confirm these findings.
Development and validation of a nomogram for prediction of the risk of positive hidden blood loss in the perioperative period of single-level thoracolumbar burst fracture
Authors: Wang Haosheng , Fan Tingting , Tang Zhi-Ri , Li Wenle , Liu Linjing , Lin Qiang 
Published: September 2021

Abstract
Background
This study aimed to develop and validate an individualized nomogram to predict the risk of positive hidden blood loss (HBL) in patients with single-level thoracolumbar burst fracture (TBF) during the perioperative period.

Methods
We conducted a retrospective investigation including 150 consecutive patients with TBL, and the corresponding patient data was extracted from March 2013 to March 2019. The independent risk factors for positive HBL were screened using univariate and multivariate logistic regression analyses. According to published literature and clinical experience, a series of variables were selected to develop a nomogram prediction model for positive HBL. The area under the receiver operating characteristic curves (AUC), C-index, calibration plot, and decision curve analysis (DCA) were used to evaluate the performance of the prediction model. Bootstrapping validation was performed to evaluate the performance of the model.

Results
Among the 150 consecutive patients, 62 patients were positive for HBL (38.0%). The multivariate logistic regression analysis showed that the six risk factors of age, length of surgical incision, duration of operation, percentage of vertebral height restoration (P1%), preoperative total cholesterol, and preoperative fibrinogen were independent risk factors of positive HBL. The C-index was 0.831 (95% CI 0.740–0.889) and 0.845 in bootstrapping validation, respectively. The calibration curve showed that the predicted probability of the model was consistent with the actual probability. Decision curve analysis (DCA) showed that the nomogram had clinical utility.

Conclusion
Overall, we explored the relationship between the positive HBL requirement and predictors. The individualized prediction model for patients with single-level TBF can accurately assess the risk of positive HBL and facilitate clinical decision making. However, external validation will be needed in the future.
The effect of preoperative hypoalbuminemia on complications after primary hip arthroplasty
Authors: Tan Yang , Jiang Lingxiao , Liu Hankun , Pan Zhengqi , Wang Hua , Chen Liaobin 
Published: September 2021

Abstract
Objectives
To explore the risk factors of preoperative hypoalbuminemia and its’ effects on complications in the elderly with primary hip arthroplasty.

Methods
A total of 211 elderly inpatients who underwent hip arthroplasty were collected. All patients were divided into the control group (preoperative serum albumin ≥35 g/L) and case group (preoperative serum albumin <35 g/L). The risk factors of preoperative hypoalbuminemia and the postoperative complications were analyzed.

Results
Compared to controls, hypoalbuminemia patients were older (P = 0.026), had lower BMI (P = 0.045), higher cardiac function score (P < 0.0001), higher ASA scores (P = 0.023), and longer hospital stay (P < 0.001). The intraoperative albumin loss in the case group was significantly higher than that of in control group (P < 0.001), but there was no significant difference in operation time and intraoperative blood loss between the two groups (P >0.05). Compared to controls, hypoalbuminemia patients had a higher risk for any complication (P = 0.014), such as delayed wound healing, pleural effusion, and pneumonia. The risk of postoperative complications increased by 6.9% with every 1 year old is increasing (age > 60). The risk of postoperative complications in the case group was 1.89 times higher than that in the control group.

Conclusion
Patients with older age, poor nutritional status, and more than 2 concomitant diseases are more likely to develop preoperative hypoalbuminemia. Preoperative hypoalbuminemia is related to the increased incidence of postoperative complications. Perioperative albumin loss is not only due to perioperative blood loss, but also related to vascular permeability and abnormal albumin metabolism.
Recombinant TSG-6 protein inhibits the growth of capsule fibroblasts in frozen shoulder via suppressing the TGF-β/Smad2 signal pathway
Authors: Liu Zhongfan , Pei Yongrong , Zeng Hao , Yang Yibo , Que Meng , Xiao Yuhui , Wang Jing , Weng Xiaojun 
Published: September 2021

Abstract
Background
The tumor necrosis factor-stimulated gene-6 (TSG-6) has been confirmed to inhibit inflammation. It is now generally accepted that local inflammatory stimulation around shoulder capsule causes proliferative fibrosis. This study aims to investigate the mechanism of recombinant TSG-6 protein inhibiting the growth of capsule fibroblasts in frozen shoulder via the TGF-β/Smad2 signal pathway.

Methods
Human frozen shoulder capsule tissue was taken for primary and passage culture, and the 3rd generation fibroblasts from pathological frozen shoulder capsule were treated with different concentrations of recombinant TSG-6 protein, or with TGF-β1 agonist SRI-011381. Immunoconfocal analysis was used to identify the isolated fibroblasts, and MTT assay, colony formation assay, and flow cytometry were used to detect the viability, proliferation, and apoptosis rate of fibroblast. The contents of fibrosis and inflammation indexes COL1A1, TNF-α, IL-6, and IL-1β in the cell supernatant were detected using ELISA and then further examined by qRT-PCR. The expression of Bax, Bcl-2, and proteins related to TGF-β/Smad2 pathway were detected by Western Blot.

Results
Compared with the blank control group, fibroblasts intervened with TSG-6 (2 μg and 5 μg) showed significantly decreased viability and proliferation ability and enhanced cell apoptosis, concurrent with the reductions in Bcl-2 expression; COL1A1, TNF-α, IL-6, and IL-1β levels; and the expression of TGF-β1 and phosphorylated Smad22, and an increase in Bax expression, while SRI-011381 treatment would reverse the effect of recombinant TSG-6 protein.

Conclusion
Recombinant TSG-6 protein inhibited the growth of primary fibroblasts from human frozen shoulder capsule by suppressing the TGF-β/Smad2 signaling pathway.
Comparison of systemic immune-inflammation index (SII), early warning score (ANDC) and prognostic nutritional index (PNI) in hospitalized patients with malignancy, and their influence on mortality from COVID-19
Authors: Bilge Muge , Akilli Isil Kibar , Karaayvaz Ekrem Bilal , Yesilova Aylia , Kart Yasar Kadriye 
Published: September 2021

Abstract
Introduction
We evaluated several biological indicators based on inflammation and/or nutritional status, such as systemic immune-inflammation index (SII), early warning score (ANDC) and prognostic nutritional index (PNI) in hospitalized COVID-19 patients with and without malignancies for a prognostic significance.

Methodology
This is a retrospective and observational study on 186 patients with SARS-CoV-2, who were diagnosed with COVID-19 by real-time PCR testing and hospitalized due to COVID-19 pneumonia. 75 patients had various malignancies, and the rest (111), having a similar age and comorbidity profile based on propensity score matching, had no malignancy.

Results
None of the measures as neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, monocyte to lymphocyte ratio, SII, PNI or ANDC was found to be significantly different between two groups. Odds ratio for the mortality, OR 2.39 (%95 CI 1.80–3.16) was found to be significantly higher for the malignancy group, even though the duration of hospitalization was statistically similar for both groups. PNI was found to be significantly lower for deceased patients compared with survivors in the malignancy group. Contrarily, ANDC was found to be significantly higher for deceased patients in the malignancy group.

Conclusions
PNI and ANDC have independent predictive power on determining the in-hospital death in COVID-19 malignancy cases. It is suggested that ANDC seems to be a more sensitive score than SII in COVID-19 cases with malignancies.
Arginine vasopressin in the medial amygdala causes greater post-stress recruitment of hypothalamic vasopressin neurons
Authors: Tong Wen Han , Abdulai-Saiku Samira , Vyas Ajai 
Published: September 2021

AbstractArginine vasopressin (AVP) is expressed in both hypothalamic and extra-hypothalamic neurons. The expression and role of AVP exhibit remarkable divergence between these two neuronal populations. Polysynaptic pathways enable these neuronal groups to regulate each other. AVP neurons in the paraventricular nucleus of the hypothalamus increase the production of adrenal stress hormones by stimulating the hypothalamic–pituitary–adrenal axis. Outside the hypothalamus, the medial amygdala also contains robust amounts of AVP. Contrary to the hypothalamic counterpart, the expression of extra-hypothalamic medial amygdala AVP is sexually dimorphic, in that it is preferentially transcribed in males in response to the continual presence of testosterone. Male gonadal hormones typically generate a negative feedback on the neuroendocrine stress axis. Here, we investigated whether testosterone-responsive medial amygdala AVP neurons provide negative feedback to hypothalamic AVP, thereby providing a feedback loop to suppress stress endocrine response during periods of high testosterone secretion. Contrary to our expectation, we found that AVP overexpression within the posterodorsal medial amygdala increased the recruitment of hypothalamic AVP neurons during stress, without affecting the total number of AVP neurons or the number of recently activated neurons following stress. These observations suggest that the effects of testosterone on extra-hypothalamic AVP facilitate stress responsiveness through permissive influence on the recruitment of hypothalamic AVP neurons.
The phosphorylation status of eukaryotic elongation factor-2 indicates neural activity in the brain
Authors: Yoon Sang Ho , Song Woo Seok , Oh Sung Pyo , Kim Young Sook , Kim Myoung-Hwan 
Published: September 2021

AbstractAssessment of neural activity in the specific brain area is critical for understanding the circuit mechanisms underlying altered brain function and behaviors. A number of immediate early genes (IEGs) that are rapidly transcribed in neuronal cells in response to synaptic activity have been used as markers for neuronal activity. However, protein detection of IEGs requires translation, and the amount of newly synthesized gene product is usually insufficient to detect using western blotting, limiting their utility in western blot analysis of brain tissues for comparison of basal activity between control and genetically modified animals. Here, we show that the phosphorylation status of eukaryotic elongation factor-2 (eEF2) rapidly changes in response to synaptic and neural activities. Intraperitoneal injections of the GABA A receptor (GABAAR) antagonist picrotoxin and the glycine receptor antagonist brucine rapidly dephosphorylated eEF2. Conversely, potentiation of GABAARs or inhibition of AMPA receptors (AMPARs) induced rapid phosphorylation of eEF2 in both the hippocampus and forebrain of mice. Chemogenetic suppression of hippocampal principal neuron activity promoted eEF2 phosphorylation. Novel context exploration and acute restraint stress rapidly modified the phosphorylation status of hippocampal eEF2. Furthermore, the hippocampal eEF2 phosphorylation levels under basal conditions were reduced in mice exhibiting epilepsy and abnormally enhanced excitability in CA3 pyramidal neurons. Collectively, the results indicated that eEF2 phosphorylation status is sensitive to neural activity and the ratio of phosphorylated eEF2 to total eEF2 could be a molecular signature for estimating neural activity in a specific brain area.
Brain-derived neurotrophic factor produced long-term synaptic enhancement in the anterior cingulate cortex of adult mice
Authors: Miao Hui-Hui , Miao Zhuang , Pan Ji-Gang , Li Xu-Hui , Zhuo Min 
Published: September 2021

AbstractPrevious studies have demonstrated that brain-derived neurotrophic factor (BDNF) is one of the diffusible messengers for enhancing synaptic transmission in the hippocampus. Less information is available about the possible roles of BDNF in the anterior cingulate cortex (ACC). In the present study, we used 64-electrode array field recording system to investigate the effect of BDNF on ACC excitatory transmission. We found that BDNF enhanced synaptic responses in a dose-dependent manner in the ACC in C57/BL6 mice. The enhancement was long-lasting, and persisted for at least 3 h. In addition to the enhancement, BDNF also recruited inactive synaptic responses in the ACC. Bath application of the tropomyosin receptor kinase B (TrkB) receptor antagonist K252a blocked BDNF-induced enhancement. L-type voltage-gated calcium channels (L-VGCC), metabotropic glutamate receptors (mGluRs), but not NMDA receptors were required for BDNF-produced enhancement. Moreover, calcium-stimulated adenylyl cyclase subtype 1 (AC1) but not AC8 was essential for the enhancement. A selective AC1 inhibitor NB001 completely blocked the enhancement. Furthermore, BDNF-produced enhancement occluded theta burst stimulation (TBS) induced long-term potentiation (LTP), suggesting that they may share similar signaling mechanisms. Finally, the expression of BDNF-induced enhancement depends on postsynaptic incorporation of calcium-permeable AMPA receptors (CP-AMPARs) and protein kinase Mζ (PKMζ). Our results demonstrate that cortical BDNF may contribute to synaptic potentiation in the ACC.