bluuebunny/crossref_metadata_2025 huggingface dataset:
Sodium tanshinone IIA sulfonate protects Myocardium from Ischemia/ Reperfusion Injury in Mice via AKT- and SIRT1/TLR4-related Mechanisms
Authors: Ding Hua-Sheng , Qu Fu-Ji , Li Qiu-Jian , Luo Zhi-Hui , Peng Yi , Wang Feng-Yuan , Zhong Peng , Huang Yan , Liu Xiao-Xiong
Published: August 2022

Background
Cardiac ischemia-reperfusion (I/R) injury is highly related to ischemic heart disease which is the main cause of death worldwide. However, no standard therapy for I/R is available. Sodium tanshinone IIA sulfonate (STS) has been demonstrated to play an important role in myocardial I/R injury, however its therapeutic effects and potential mechanism remain still unclear. This study was aimed to investigate the potential protective effects of STS on myocardial I/R injury.
Methods
STS were injected intraperitoneally at 30 mg/kg per mouse beginning 10 days before I/R surgery. Histological analyses and markers, echocardiographic parameters, TTC staining were examined to assess myocardial injury.
Results
Compared with I/R mice, I/R in STS-administered mice leaded to diminished myocardial infarct size, apoptosis, and toll-like receptor 4 (TLR4) expression. In cultured cardiomyocytes, STS inhibits apoptosis and production of TLR4, IL-6. Dominant negative AKT reversed the inhibitory effect of STS on apoptosis, but had no effect on the inhibitory effect of STS on IL-6 production. STS induces SIRT1/TLR4-dependent anti-inflammation in cardiomyocytes, and inhibition of SIRT1 by siSIRT1 reverses the inhibitory effect of STS on inflammation and infarct size.
Conclusion
Our study suggest that STS can relieve heart I/R injury through AKT and SIRT1/TLR4-dependent mechanisms in vivo and vitro.
Wetland conservation and management practices in Rubanda District, South-Western Uganda
Authors: Turyasingura Benson , Alex Saturday , Hirwa Hubert , Mohammed Fatima Sule
Published: August 2022

Worldwide, wetlands cover about 9% of the land surface and are recognized as bio-networks that offer living prospects when managed properly. Despite the present resource management regime, many wetlands in Uganda are being degraded due to mining, construction, agricultural and industrial activity, and little attention has been paid to the effectiveness of wetland conservation. The goal of this research was to evaluate Nyamuriro wetland conservation and management practices in Rubanda District, Uganda. The study was guided by specific objectives, which included investigating the management approaches used in Nyamuriro wetland conservation, identifying the management challenges preventing Nyamuriro wetland conservation, and evaluating sustainable solutions to the challenges preventing Nyamuriro wetland conservation. The study employed a descriptive cross-sectional research design that included qualitative and quantitative data gathering and analysis techniques. A total of 109 people participated in the study using simple random and purposive sampling approaches. In this study, data was collected using questionnaires, key informant interviews, and observational approaches. Most respondents strongly agree that wetland restoration is the best management approach for Nyamuriro wetland conservation (Mean = 4.87, SD = 0.547). Corruption was the most significant hindrance to the conservation of Nyamuriro wetland among the management problems (Mean = 3.41, SD = 0.467). Overall, the data showed that there was a significant positive association between conservation management techniques but not between viable Nyamuriro wetland conservation measures. The study recommended that strict laws and procedures should be put in place to ease restrictions on wetland conservation.
Convergent, slightly misoriented crystals toughen corals and seashells
Authors: Gilbert Pupa , Lew Andrew , Stifler Cayla , Tits Alexandra , Schmidt Connor , Luffey Emily , Scholl Andreas , Cantamessa Astrid , Muller Laura , Delaunois Yann , Compère Philippe , Ruffoni Davide , Buehler Markus
Published: August 2022

The hardest and toughest tissues formed by living organisms are organic-mineral composites termed biominerals 1,2. When they are crystalline, their mesostructure includes the nano- and micro-scale crystallite size, shape, arrangement, and orientation. Mesostructures vary enormously across marine CaCO3 biominerals (aragonite, vaterite, calcite) because they result from divergent evolution: biominerals were formed long after organisms diverged from one another 3,4. Despite such diversity, CaCO3 marine biominerals share a convergent character: adjacent crystals are similarly oriented 5-32. The reason for such convergence is unclear. Here, we show with quantitative, precise measurements at the nanoscale that the slight misorientation is consistently between 1°-40° in diverse biominerals. Can this slight misorientation confer a desirable materials property and therefore an evolutionary advantage to the forming organisms? We test and confirm this hypothesis with nanoindentation in diverse biominerals, geologic aragonite, and in abiotic, slightly misoriented, synthetic spherulites. Molecular dynamics (MD) simulations of bicrystals reveal that aragonite, vaterite, calcite, exhibit toughness peaks when they are misoriented by 10°, 20°, 30°, respectively, demonstrating that slight misorientation alone increases crack deflection and therefore fracture toughness. Slight misorientation, along with other previously known and co-existing toughening mechanisms, was selected repeatedly and convergently, during the course of evolution, to postpone fracture and thus provide organisms with competitive advantage. We anticipate slight misorientation-toughening to be a starting point for more sophisticated materials synthesis and additive manufacturing in many fields. Compared to previously known toughening mechanisms, in fact, the advantages of slight misorientation are that it can and does occur in synthetic materials, it requires one material only and no specific top-down architecture, it is easily achieved by self-assembly of organic molecules (e.g. aspirin, chocolate), polymers, metals, and ceramics 29 well beyond biominerals.
IoT-Based Data-Driven Predictive Maintenance Relying on Fuzzy System and Artificial Neural Networks
Authors: Aboshosha Ashraf , Haggag Ayman , George Neseem , Hamed Hisham A.
Published: August 2022

Industry 4.0 technologies need to plan reactive maintenance and Preventive Maintenance (PM) strategies for their production machines. However, preventive maintenance cannot predict the future faults or conditions of the machine components in advance to prevent halting the production cycle. This study aims to use a Predictive Maintenance (PdM) technology with communication technologies to counter these problems. Sensors Information Modeling (SIM) and the Internet of Things (IoT) have the potential to improve the efficiency of industrial production machines maintenance management. They can provide a better maintenance strategy utilizing a data-driven predictive maintenance planning framework based on our proposed SIM and IoT technologies. Data is collected and integrated with the proposed (SIM) models and the IoT network. The proposed system consists of the data entry form that contains all the measurements, notes of events that are difficult to electronically monitor, and the credibility of data measured by sensors. The status and performance of the machine are continuously being monitored as they consciously vary according to the operating conditions. Data collection from the SIM models, and IoT network are integrated in a software framework that consists of, (1) condition and performance monitoring and faults module, (2) machine condition evaluation module, (3) failure prediction module, (4) maintenance decision module. Machine learning algorithms and artificial neural networks are used to detect the healthy or faulty operating conditions and predict probability of failures, evaluate the conditions of the machine components and estimate the remaining lifetime. To verify the feasibility of our approach, our proposed framework is applied to a corrugated board production factory real industrial environment. The results show that, updated data obtained from the information layer with machine learning algorithms in the application the layer can effectively predict the future state of the machine components to make appropriate maintenance decisions.
Lactobacillus fermentum (MTCC-5898) based fermented whey renders prophylactic action against colitis by strengthening the gut barrier function and maintaining immune homeostasis
Authors: Kaur Harpreet , Gupta Taruna , Kapila Suman , Kapila Rajeev
Published: August 2022

Nutritional intervention using probiotic fermented dairy product has emerged as a promising therapeutic strategy to curb inflammatory bowel diseases. The present study was aimed to investigate the prophylactic capability of probiotic Lactobacillus fermentum (LF:MTCC-5898) fermented whey on impaired barrier function in DSS induced mice. Probiotic fermented whey (PFW) consumption improved the symptoms of colitis-associated with intestinal inflammation by significantly (p < 0.01) diminishing the percent loss in body weight, disease activity index and spleen index with improvement in colon length and weight besides hematological and histopathological score. Likewise, pre-treatment with PFW improved the barrier integrity (p < 0.01) in contrast to leaky condition induced by DSS administration characterized with increased permeability of FITC-dextran (451 ± 225.1) across epithelium. PFW consumption also provided the gut immune protection that occurred via significant increase (p < 0.05) in TLR-2 expression and stimulated T-regulatory response by producing TGF-β (p < 0.01), to potently suppress (p < 0.01) induced inflammatory response markers (TNF-α, IL-4 and C-reactive protein). Consistently, in preventive way, PFW intake significantly enhanced (p < 0.05) immunoglobulin (sIgA) secretion and concomitantly restored the Occludin, ZO-1 (p < 0.01), Claudin-1(p < 0.05) transcriptional expression as compared to colitis mice. Additionally, immune-fluorescence further established the presence of intact actin cytoskeleton and tight junction proteins (claudin-1, occludin and ZO-1) after PFW consumption. Thus, PFW rectified the impaired and leaky barrier junctions not only through modulation of transcriptional expression of tight junction genes but also with reduced secretion of inflammatory mediators and helped in ameliorating the colitis. Hence, probiotic fermented whey could be used as potential prophylactic functional food in the prevention of gut ailments.
Fig latex inhibits the growth of pathogenic bacteria invading human diabetic wounds and accelerating the wound closure in diabetic mice
Authors: Salah Mohamed , Badr Gamal , Hetta Helal F. , Khalifa Walaa A. , Shoreit Ahmed A.
Published: August 2022

Impaired wound healing is one of the most critical complications associated with diabetes mellitus. Hence, novel and more effective natural therapeutic antibacterial agents are urgently needed and should be developed against the pathogenic bacteria inhabiting the diabetic wounds. Therefore, the current study aimed to investigate the impact of fig latex on the pathogenic bacteria and its ability to promote the healing process of diabetic wounds. The pathogenic bacteria were isolated from patients with diabetic wounds admitted at Assiut University hospital. Fig latex was collected from trees in Assiut regions, and its chemical compositions were analyzed using GC-MS. The anti-bacterial efficacy of the fig latex was assessed on the isolated bacteria. In vivo study to investigate the effect of fig latex on the diabetic wound healing was monitored using three mice groups: non-diabetic control, diabetic and diabetic treated with fig latex. The influence of fig latex on the expression levels of β-defensin-1, collagen formation, PECAM-1, CCL2 and ZO-1 were investigated. The GC-MS analysis demonstrated the presence of triterpenoids with more than 90% of total latex content. Furthermore, using streptozotocin (STZ)-induced diabetic mice model, topical treatment of diabetic wounded tissues with fig latex accelerated and improved the wound closure through increasing the expression levels of β-defensin-1, collagen, and PECAM-1 as compared to untreated diabetic wounds. Additionally, fig latex down-regulated the expression levels of ZO-1 and CCL2.
A comparative study of panoramic radiography and cone-beam computed tomography about the relationship of mandibular third molar an inferior alveolar canal
Authors: Jian Zhang , Xiaoyu Gao , Wenyi Zhang
Published: August 2022

Purpose To evaluate the accuracy of Panoramic radiography（PAN） by using CBCT to compare the anatomical relationship between the mandibular third molar and the inferior alveolar nerve canal (IAN).Methods The research sample included the imaging information of 953 MTMs and adjacent mandibular canals were studied. Statistical software SPSS25.0 was used, and chi-square test was used to analyze the correlation between demographic factors, type of obstruction, special imaging findings of PAN and IAN canal defect in CBCT. The factors related to IAN canal defect were evaluated by Logistic regression. Results Among the 953 study subjects, 757 cases of inferior alveolar nerve canal cortical bone were intact and 196 cases of IAN canal are defect. The differences between mandibular duct wall defects in the classification of MTM, the darkening of roots, the interruption of the white line, the deviation diversion of canal, and the narrowing of canal were statistically significant. In logistic regression analysis, P&G classification (mesial-distal), the darkening of roots, and the interruption of the white line were risk factors for mandibular duct wall defects. Conclusions The interruption of the white line, darkening of the root, and the P&G classification (mesial-distal) suggest an increased rate of IAN canal defects. The special imaging manifestations related to the absence of cortical bone in the mandibular canal wall in univariate analysis, this study still recommends that further detailed investigation of CBCT is recommended.
Genotyping of cerebrospinal fluid for leptomeningeal metastases in EGFR-mutated lung cancer
Authors: Geng Di , Niu Ruina , Li Jinghong , Guo Sanxing , Guo Qianqian , Huang Siyuan , Wang Yurong , Li Xingya
Published: August 2022

Background: Leptomeningeal metastasis (LM) is a detrimental complication of advanced lung cancer, more frequently occurring in patients harboring epidermal growth factor receptor (EGFR) mutation. Due to limited access to the leptomeningeal lesion, we explored the potential role of cerebrospinal fluid (CSF) as a source for liquid biopsy in LM patients with EGFR mutation.Materials and methods: The CSF samples from Lung cancer patients with LM were collected between June 2021 and August 2018 at First Affiliated Hospital of Zhengzhou University. Next-generation sequencing was performed to detect the mutations in EGFR genes, overall 38 patients detected with EGFR mutations were finally enrolled in further retrospectively clinical analyses.Results: CSF samples of 38 lung patients with LM harboring EGFR mutation were enrolled in this study.we found 20 cases of L858R of exon 21 and 14 cases of exon 19 deletion.Other EGFR mutations included EGFR exon 20 insertion(n=1),EGFR G719A of exon 18 (n=1) ,EGFR G719S of exon 18 (n=1), EGFR S768I of exon 20 and G719C of exon 18(n=1).CSF samples from 6 patients were collected before prescribing them TKIs.The most frequently detected concurrent genes in CSF was TP53 missense mutation(50%).CSF of 10 patients were obtained after failure to 1st TKI.The most frequently detected concurrent genes in CSF were TP53 missense mutation(40%,n=4),EGFR copy number amplification (40%,n=4) and NKX2-1 copy number gain(30.0%,n=3).Acquired resistance to 1st TKI of T790M mutation was detected in two patients. Similarly, the CSF samples from 22 patients were collected during their 3rd TKI therapy and the TP53 missense mutation was detected in 31.8% of patients followed by EGFR amplification (22.7%), STK11 deletions (18.2%) and MYC amplification (18.2%), while two patients harbored T790M mutation. Known mechanisms of acquired resistance to EGFR- 3rd TKIs were identified in 31.8% of cases. C797S and C797G mutation was found in three patients.Possible EGFR-independent resistant mechanism included PIK3CA missense mutation(4.5%),MET amplification(4.5%),CDK4 amplification(4.5%) and RET gene fusion(4.5%).In the 38 cases , average TMB was 8.4mutations/Mb (median 6.9 , range 1.1-23.83mutations/Mb) ,12 cases with more than 10 mutations/Mb. There were no significant difference of CSF TMB among the three group of patients who hadn’t received TKI, progressed on 1st TKI and progressed on 3rd TKI.Conclusion: CSF cfDNA provided comprehensive profiles of driver and resistance genes of lung cancer with LM harboring EGFR mutation, supporting the importance of CSF cfDNA as a liquid biopsy medium and guiding the choice of anti-tumor drugs.
Exosomal MicroRNAs modulate the cognitive function in fasudil treated APPswe/PSEN1dE9 transgenic (APP/PS1) mice model of Alzheimer's disease
Authors: Yan Yuqing , Gao Ye , Kumar Gajendra , Fang Qingli , Zhang Nianping , Yan Hailong , Zhang Yuna , Song Lijuan , Li Jiehui , Zheng Yucheng , Zhang Nan , Zhang Han-Ting , Ma Cungen
Published: August 2022

Alzheimer’s disease (AD) is characterized by cognitive impairment caused by the accumulation of beta-amyloid (Aβ) plaques and trans-synaptic spread of tau pathology. Exosome has emerged as key mediators for neuronal development, maintenance, and cellular communication. However, the molecular mechanism of exosomal miRNAs related to AD remains unknown. In the present study, APPswe/PSEN1dE9 transgenic (APP/PS1) mice (AD) were treated with vehicle (ADNS) and fasudil (ADF), whereas C57BL/6 (control) mice were treated with vehicle (WT). Cognitive function was assessed by Y-maze test and AD pathology was confirmed by immunostaining of Aβ plaque and phosphorylated tau. Exosomal RNAs from each mouse of the group were extracted, sequenced and analyzed. Our results showed amelioration of cognitive function, decreased Aβ plaque load, and phosphorylated tau protein after fasudil treatment. Exosomal miRNA analysis showed 3 miRNAs (mmu-let-7i-5p, mmu-miR-19a-3p, mmu-miR-451a) in the intersection of ADNS vs ADF and WT vs ADNS. GO annotation and KEGG pathway showed the target gene of miR-19a-3p are Pten and Tnf; mmu-miR-451a are Nsmaf, Gnai3 and Akt3. In conclusions, fasudil treatment improved cognitive function by regulating exosomal MicroRNAs (mmu-miR-451a and mmu-miR-19a-3p). These MicroRNAs could be potential biomarker of AD and therapeutic target for novel treatment for AD.
Certification as dysplasia unit and its impact on large loop electrosurgical excision (LEEP)
Authors: Hanczuk Tatjana , Weiss Martin , Henes Leon , Engler Tobias , Neis Felix , Henes Melanie
Published: August 2022

Purpose
This study evaluates the overall treatment indicators and outcomes of patients who underwent loop electrosurgical excision procedure (LEEP) at the Department of Women’s Health Tübingen and the impact of certification as a dysplasia unit on treatment quality.
Methods
Retrospective analysis of data from 1596 patients from 2013 to 2018 who underwent LEEP excision at the Department of Women’s Health Tübingen. Data of cytology, colposcopy, biopsy, LEEP histology, repeat LEEP histology and general characteristics were collected and analyzed descriptively.
Results
A total of 85.4% (1364) had CIN 2 + and 14.6% (232) had CIN 1 or normal findings on LEEP histology. The proportion of CIN 2 + excisions increased significantly from 82.4% in 2013 to 89% in 2018. The concordance of HSIL biopsy and LEEP histology was 89.1% in 2013 and 92.6% in 2018. In 2018, more biopsies and colposcopies were performed before excision. Complete resection (R0) was achieved in 88.3% of all excisions. R0 rates in patients with CIN 3 increased in 2014–2017 compared to 2013, resulting fewer Re-LEEP excisions and hysterectomies.
Conclusion
Certification as a dysplasia unit and the associated requirements have resulted an increase of quality for patients with cervical dysplasia undergoing LEEP. This was demonstrated by several treatment indicators such as the number of colposcopies and biopsies and treatment outcomes such as increased proportion of CIN 2 + excisions and R0 resections.
Could an Earth-mass planet have existed between Jupiter and Saturn?
Authors: Dvorak R. , Cuntz M.
Published: August 2022

Motivated by previous studies about asteroids situated between Jupiter and Saturn, where long-term stable orbits with small eccentricities and low inclinations have been identified, we extend this research by placing an Earth-mass planet in the region between Jupiter and Saturn. We pursued numerical integrations of the equations of motions for the outer solar system encompassing Jupiter, Saturn, Uranus, and Neptune, as well as the additional Earth-mass planet. This 6-body system has been integrated with the Lie method for up to 500 Myr. The default initial stable zone for the Earth-mass planet has been assumed between 7.04 au and 7.31 au based on the results from previous studies by our group. We explored each region separately for 360 Earth-mass planets (assuming different mean anomalies) and inspected the respective escape times (ETs). The overall picture shows that the most stable orbits occur between 7.12 au and 7.28 au. Furthermore, the mean of the ETs for all 360 mean anomalies between 7.24 au and 7.12 au gradually decreases from ET=11 Myr to 0.9 Myr, although smaller values are obtained for the median due to outliers. To check the role of stability of the Earth-mass planet depending on its initial inclination, we focused on three regions (i.e., 7.23 au, 7.24 au, and 7.25 au) in terms of their ETs assuming i = 1°, 3°, and 5°; however, no significant differences were found. Hence, the general possibility of an Earth-mass planet situated between Jupiter and Saturn in the Solar System’s distant past is highly notable, although it would have been a transient event.
Selfing species has greater genetic diversity and less structure than related outcrossing species due to seed dispersal and population history
Authors: Zhao Jian-Li , Shao Guo-Jun , Sork Victoria , Wang Ya-Li , Li Li , Chen Hong-Fan , Wang Wen-Jing , Huang Mei-Yuan , Li Qingjun
Published: August 2022

Mating system is a crucial factor shaping the amount of genetic diversity and the fine-scale spatial genetic structure (FSGS), with selfing species usually having less diversity and stronger FSGS than outcrossing species. Such general conclusions resulted from comparisons among distant species, often neglecting consideration of co-effects of the population history, microhabitat and seed dispersal in different habitats. This study used two species in the genus Roscoea (Zingiberaceae) with contrasting mating systems to explore the formation of FSGS. Using thousands of single nucleotide polymorphisms (SNPs) found in outcrossing Roscoea cautleoides (RC) and selfing R. schneideriana (RS) located in different habitats from same region, we compared genetic diversity, FSGS and historical population dynamics between outlier (non-neutral) SNPs and neural SNPs, integrating with field observation of seed dispersal distance. RC has lower genetic diversity and showed stronger FSGS than RS, which conflicted with the general expectations. Outlier SNPs exhibited significantly larger genetic diversity and genetic differentiations among individuals within population suggested adaptive divergence to different microhabitats. Both RC and RS experienced bottlenecks that are consistent with the Last Glacial Maximum (~21 kyrs) and the last second Glacial Maximum (~150 kyrs), respectively. Field investigation indicated seeds of RS were transported from stock plants by ant significantly further than seeds of RC. Our results indicate that seed dispersal, different historical population dynamics, and environmental heterogeneity can over-ride the initial impact of pollen dispersal.
Recombinase Polymerase Amplification Assay with Lateral Flow Strips for Rapid Diagnosis of Candidiasis due to Candida parapsilosis
Authors: Wang Kun , Fan Shihui , Li Yuanyuan , Huo Li , Wang Yan , Wang Xizhen , Wang Lei
Published: August 2022

Background
Candida parapsilosis is a common cause of candidiasis among hospitalized patients, often surpassing Candida albicans. Due to the recent increase in C. parapsilosis infections, there is an urgent need for rapid, sensitive, and real-time on-site detection of nucleic acids for timely diagnosis of candidiasis.
Methods
We developed an assay for detection of C. parapsilosis by combining recombinase polymerase amplification (RPA) with a lateral flow strip (LFS). The RPA-LFS assay was used to amplify the beta-1,3-glucan synthase catalytic subunit 2 (FSK2) gene of C. parapsilosis with a primer-probe set optimized by introducing base mismatches (4 bases modified by the probe and one by the reverse primer) to achieve specific and sensitive detection of clinical samples.
Results
The RPA assays can rapidly amplify and visualize a target gene within 30 min, while the entire process can be completed within 40 min by pre-processing the sample.The sensitivity and specificity of the RPA-LFS assay were determined by analysis of 35 common clinical pathogens and 281 clinical samples against quantitative PCR.
Conclusions
The results confirmed that the proposed RPA-LFS assay is a reliable molecular diagnostic method for the detection of C. parapsilosis to meet the urgent need for rapid, specific, sensitive, and portable field testing.
Plasma host protein signatures correlating with Mycobacterium tuberculosis activity prior to and during antituberculosis treatment
Authors: NDIAYE Mame Diarra Bousso , RANAIVOMANANA Paulo , RASOLOHARIMANANA Tsikiniaina , RASOLOFO Voahangy , RATOVOSON Rila , HERINDRAINY Perlinot , RAKOTONIRINA Julio , SCHOENHALS Matthieu , HOFFMANN Jonathan , RAKOTOSAMIMANANA Niaina
Published: August 2022

Background
There is a need for rapid non-sputum-based tests to identify and treat patients infected with Mycobacterium tuberculosis (Mtb). In this study, performance of a human plasma protein signature for both TB triage and treatment monitoring has been evaluated.
Methods
A panel of seven host proteins CLEC3B, SELL, IGFBP3, IP10, CD14, ECM1 and C1Q were measured in the plasma of a prospective patient cohort undergoing anti-tubercular therapy to distinguish confirmed TB patients from control, to define culture slow and fast converters during an antituberculosis treatment and to monitor the treatment. To validate the protein signatures a Luminex xMAP® assay was used to quantify the proteins in unstimulated plasma isolated from the blood collected from HIV-negative pulmonary TB patients (ATB), at baseline and following 6-months of antituberculosis treatment, latently TB-infected individuals (LTBI) and healthy donors (HD). Protein signatures performances were evaluated using CombiROC algorithm and multivariate models.
Findings:
We measured the proteins in the plasma of 84 participants including 37 ATB, 24 LTBI and 23 HD. The seven plasma host proteins studied showed different levels between the TB clinical groups and when used separately or in combination, have variable performances for ATB triage and for treatment monitoring. Six of the plasma proteins (CLEC3B, SELL, IGFBP3, IP10, CD14 and C1Q) showed significant differences in normalised median fluorescence intensities when comparing ATB vs HD or LTBI while ECM1 revealed a significant association with early sputum culture conversion after 2 months following treatment (OR 0.004, p = 0.018). For both triage and treatment monitoring, a signature combining 4 host proteins markers (CLEC3B-ECM1-IP10-SELL) was identified, allowing to distinguish ATB from HD or LTBI (respectively, sensitivity = 94%, specificity = 92% and sensitivity = 89%, specificity = 91%) as well as the baseline distinction between slow vs fast sputum culture converters after two months of treatment (AUC = 0.87, sensitivity = 83%, specificity = 84%).
Conclusion
Our data demonstrate that using a combination of host plasma markers can generate a relevant biosignature for both TB triage and treatment monitoring meeting the WHO Target Product Profile for both purposes.
Design and validation of a multi-task, multi-phase protocol for real-world gait simulation
Authors: Scott Kirsty , Bonci Tecla , Francesca Salis , Alcock Lisa , Buckley Ellen , Gazit Eran , Hansen Clint , Schwickert Lars , Aminian Kamiar , Bertuletti Stefano , Caruso Marco , Chiari Lorenzo , Sharrack Basil , Maetzler Walter , Becker Clemens , Haussdorff Jeffrey M. , Vogiatzis Ioannis , Brown Philip , Din Silvia Del , Eskofier Björn , Paraschiv-Ionescu Anisoara , Keogh Alison , Cameron Kirk , Kluge Felix , Micó-Amigo M. Encarna , Mueller Arne , Neatrur Isabel , Niessen Martijn , Palmerini Luca , Sillen Henrik , Singleton David , Ullrich Martin , Vereijken Beatrix , Froelich Marcel , Brittan Gavin , Caulfield Brian , Koch Sarah , Carsin Anne-Elie , Garcia-Aymerich Judith , Kuederle Arne , Yarnall Alison , Cereatti Andrea , Mazzà Claudia
Published: August 2022

Background: Measuring mobility in daily life entails dealing with confounding factors arising from multiple sources, including pathological characteristics, patient specific walking strategies, environment/context, and purpose of the task. The primary aim of this study is to propose and validate a multi-task and multi-phase protocol for simulating real-world gait accounting for all these factors within a single set of observations carried out within a limited laboratory space, while ensuring minimisation of participant burden and safety.Methods: The protocol included eight motor tasks at varying speed, incline/steps, surface, path shape, cognitive demand, and included postures that may abruptly alter the participants’ strategy of walking. It was deployed in a convenience sample of 108 participants recruited from six cohort groups that included older healthy adults (HA) and participants with potentially altered mobility due to Parkinson’s Disease (PD), Multiple Sclerosis (MS), Proximal Femoral Fracture (PFF), Chronic Obstructive Pulmonary Disease (COPD) or Congestive Heart Failure (CHF). A novelty introduced in the protocol was the tiered approach to increase difficulty both within the same task (e.g., by allowing use of aids or armrests) and across tasks.Results: The protocol proved to be safe and feasible and the addition of the more complex tasks allowed a much greater spread in walking speeds to be achieved compared to standard straight walking trials. Furthermore, it allowed a relatively realistic representation of daily life relevant mobility aspects and can therefore be used for the validation of monitoring devices used in real life.Conclusions: The suitability of the protocol for measuring gait in a variety of pathological conditions suggests that it can also be used to detect changes in gait due to, for example, the onset or progression of a disease, or due to therapy.Trial registration: ISRCTN – 12246987.
Successful treatment of Balamuthia mandrillaris granulomatous amoebic encephalitis with the novel agent nitroxoline
Authors: Spottiswoode Natasha , Pet Douglas , Kim Annie , Gruenberg Katherine , Shah Maulik , Ramachandran Amrutha , Laurie Matthew , Zia Maham , Fouassier Camille , Boutros Christine , Lu Rufei , Zhang Yueyang , Servellita Venice , Bollen Andrew , Chiu Charles , Wilson Michael , Valdivia Liza , DeRisi Joseph
Published: August 2022

This case report describes a survivor of Balamuthia mandrillaris granulomatous amoebic encephalitis (GAE) after treatment with the novel agent nitroxoline, a drug typically used to treat urinary tract infections. Nitroxoline was previously identified in a screen of US and European approved drugs for amoebicidal activity against this pathogen. We describe its successful first use in treating this rare and deadly disease.
miR-9 and miR-218 modulate α7 nicotinic acetylcholine receptors levels via targeting of RIC-3 chaperone
Authors: Roshani Shima , Azizikhoshsirat Hana , Asadi Milad , Sadigh-Eteghad Saeed , Shanehbandi Dariush
Published: August 2022

Nicotinic acetylcholine receptors (nAChRs) have a role in a variety of pathophysiological conditions. Resistant to inhibitor cholinesterase (RIC-3) is a chaperone protein responsible for proper folding and assembly of α7 subunit of nAChRs. A variety of microRNAs, including miR-9 and miR-218, affect RIC-3. Thus, in the current study, the targeting of the RIC-3 gene with miR-9 and miR-218 was investigated. HEK-293 cells were transfected with miR-9 and miR-218 pre-mature miRNAs and were subjected to qRT-PCR, luciferase assay, and western blotting. The obtained results revealed that exogenous upregulation of miR-9/miR-218 further reduced RIC-3 mRNA and protein expression. In addition, luciferase assay illustrated that miR-9/miR-218 directly binds to the specific regions in RIC-3 3’-UTR and suppresses its expression. Also, it was found that miR-9/miR-218 mediated suppression of RIC-3 led to significant decreases of α7nAChR at protein levels. In conclusion, our findings implied that miR-9 and miR-218 might be involved in the receptor related-cellular signaling through modulating the RIC-3/α7 nAChR axis.
Hydrolysis of Regenerated Cellulose from Ionic Liquids and Deep Eutectic Solvent over Sulfonated Carbon Catalysts
Authors: Kim Han Ung , Kim Jong Wha , Seo Sumin , Park Young-Kwon , Jae Jungho
Published: August 2022

The efficient hydrolysis of cellulose into its monomer unit such as glucose or valuable cello-oligosaccharides is the critical step for the cost-effective production of biofuels and biochemicals. However, the current cellulose hydrolysis process involves high energy-demanding pretreatment (e.g., ball-milling) and long reaction times (>24h). Herein, we investigated the feasibility of the dissolution/regeneration (DR) of cellulose in ionic liquids (ILs) and deep eutectic solvent (DES) as an alternative to ball-milling pretreatment for the effective hydrolysis of cellulose. Because chlorine-based solvents are reported to be most active for biomass pretreatment, [EMIM]Cl and [DMIM]DMP were selected as the IL molecules, and choline chloride-lactic acid was selected as the DES molecule. The level of the crystallinity reduction of the regenerated cellulose were analyzed by the XRD and SEM measurements. The hydrolysis kinetics of the regenerated cellulose from ILs and DES were examined at 150 °C using sulfonated carbon catalysts and compared with the ball-milled cellulose. Overall, the cellulose pretreatment using the ILs and the DES had similar or superior kinetics for cellulose hydrolysis to the conventional ball milling treatment, suggesting a possibility to replace the current high energy-demanding ball-milling process with the energy-saving DR process. In addition, the utilization of supercritical carbon dioxide-induced carbonic acid as an in-situ acid catalyst for the enhanced hydrolysis of cellulose was presented for the first time.
Description of covalent bond in terms of generalized charges. Potential and dissociation energy of homonuclear compound
Authors: Dolgonosov Anatoly M.
Published: August 2022

The theory of generalized charges is an asymptotic approximation of quantum mechanics for interatomic forces. It is based on the model of multicomponent electron gas, which extends the Thomas-Fermi model of inhomogeneous electron gas to pair electronic states. The present research takes in consideration the participation of the field of generalized charges in interatomic bonds. Herein, the definition of generalized charges (GC) by means of the overlap integral of the wave functions of valence electrons is given, and properties of GC are found out. Equations are derived for the potential and length of a homopolar bond, and dependence of these parameters on the generalized charges is shown. The dissociation energy of a diatomic molecule is expressed in terms of the nuclear charges, the function and multiplicity of the covalent bond, the angular momentum, and the vibrational energy of the binding electrons. The parametrization rules are substantiated and an a priori calculation of the dissociation energy of diatomic homonuclear molecules is carried out against the electronic configuration of the bond electrons and the nuclear charge. The calculation results for homonuclear compounds of the elements of the first four rows of the Periodic table are shown to be of satisfactory accuracy.
Preparation and Characterization of Poly (Vinyl Alcohol)/ PANI@CuS Hybrid Nanocomposites for Optoelectronic Application
Authors: Sangamesha M. A. , R Kavya , Madhukar B. S.
Published: August 2022

Inclusion of conducting polymers coated inorganic nano particles in to semiconducting host polymers opens a new window to modify physical and chemical properties of the semiconducting polymers. An in-suite polymerization method was employed for the synthesis of polyaniline (PANI) composites of with copper sulphide (PANI@CuS) and later introduced to polyvinyl alcohol (PVA). In this present work PVA/PANI@CuS hybrid nanocomposites (NCs) were prepared by eco-friendly solution casting method with varying concentration of PANI@CuS viz. 0, 1, 2, 3 and 4 wt%. the prepared polymer hybrid nanocomposites were subjected to various analytical technique to evaluate their morphological, electrical, optical and surface properties. The X-ray diffraction and FT-IR studies display the molecular interaction between CuS, PANI and PVA. UV- Visible shows reduced band gap from 6.17 to 3.43 whereas refractive index increases from 1.40–1.73 which gives the information about the optical properties furthermore, photoluminescence spectra show a stoke shift of ~ 150 nm towards higher wavelenth which opens new window for the photovoltaic applications. Scanning electron microscope (SEM) is used to study the morphology, electrical properties were analysed by DC electrical conductivity and found that the conduction mechanism follows Poole-Frenkel effect. The obtained results show that addition of PANI@CuS greatly enhances the opto-electronic properties of the host polymer matrix.
Influence of cooking methods on in vitro bioaccessibility of phenolics, flavonoids, and antioxidant activity of red cabbage
Authors: Ávila Suelen , Zalamanski Sara , Tanikawa Lilian Mitsuko , Kruger Claudia Carneiro Hecke , Ferreira Sila Mary Rodrigues
Published: August 2022

Red cabbage is rich in phytochemical compounds, and its consumption, either raw or cooked, has been linked to the prevention of several diseases. This work aimed to investigate the influence of cooking methods on in vitro bioaccessibility of phenolics and antioxidant activity of red cabbage. The vegetable was subjected to boiling, steaming, and microwaving for different times to evaluate color parameters, total phenolic (TPC), total flavonoid (TFC), anthocyanin content (AC), and antioxidant activity (FRAP, DPPH, and ABTS). The phytochemical bioaccessibility before and after cooking was also evaluated by in vitro simulated digestion. Steaming showed the most significant retention of the compounds after 20 and 25 minutes of cooking (72-86% for TPC, 72-77% for TFC, 75-79% for FRAP, 84-91% for DPPH, 70-83% for ABTS), followed by microwaving, which was more stable in 10 minutes. Microwaving decreased TFC and AC over time. Boiling did not show significant differences between the cooking times and showed more than 50% of losses of TPC, TFC, and AC and 30 to 60% of antioxidant activity. Steaming was the best cooking method, showing the most significant tendency to black coloration (< L*). In 10 minutes, it still showed the highest percentages of increase in TPC and the minor losses of TFC and AC in the gastric and intestinal phases. Steaming also increased the antioxidant after digestion when compared to uncooked red cabbage. These results are important to help consumers choose the most effective cooking method for red cabbage to retain its health-promoting components.
Application of split pancreatic drainage tube in laparoscopic pancreaticoduodenectomy
Authors: Tu Jianhua , Huang Changwen , Xu Wenyan , Gong Shuaichang , Cao Zhenjun , Wan Ping , Ying Junxiang , Rao Xuefeng
Published: August 2022

Background
Laparoscopic pancreaticoduodenectomy (LPD) is a classic surgical method for diseases, such as tumors at the lower end of the common bile duct, pancreatic head, and benign and malignant tumors of the duodenum. Postoperative pancreatic fistula (POPF) is one of the most serious complications of LPD. In this study, we introduced a separate stent drainage method to reduce the occurrence of grade B or C POPF and its related complications.
Methods
To reduce the incidence of grade B or C POPF and other complications after LPD, we applied a split pancreatic drainage tube combined with the characteristics of internal and external stent drainage. Between January 2018 and May 2022, 12 patients underwent placement of the split pancreatic drainage tube during LPD.Data on operation time, duration of pancreaticojejunostomy (PJ), intraoperative blood loss, first postoperative exhaust time, postoperative hospital stay, incidence of POPF and other complications were collected and analyzed.
Results
The average operation time was 280 ± 42 min, average time for PJ was 35 ± 6 min, and average estimated blood loss was 200 ± 40 mL. Biochemical leakage occurred in two patients (16.7%), whereas no grade B or C POPF, other related complications, and deaths occurred within 30 days after the operation.
Conclusion
Split pancreatic drainage tube effectively converts external stent drainage into internal stent drainage. It fully combines internal and external drainage characteristics, effectively reduces the incidence of postoperative POPF and other related complications of grade B or C, and provides a new choice for clinicians to make decisions.
Individualizing mechanical ventilation: Titration of driving pressure to pulmonary elastance through Young’s modulus in an acute respiratory distress syndrome animal model
Authors: Mingote Álvaro , García Ramsés Marrero , González Martín Santos , Díaz Raquel Castejón , Antón Clara Salas , Nuñez Juan Antonio Vargas , García-Fernández Javier
Published: August 2022

Background: Mechanical ventilation increases the risk of lung damage (VILI). Some authors propose that the way to reduce VILI is to find the threshold of driving pressure below which VILI is minimized. In this study, we propose a method to titrate the driving pressure to pulmonary elastance in an acute respiratory distress syndrome model using Young’s modulus and its consequences on ventilatory-induced lung injury. Material and methods: 20 Wister Han male rats were used. After generating an acute respiratory distress syndrome, two groups were studied: a) standard protective mechanical ventilation: 10 rats received 150 minutes of mechanical ventilation with driving pressure = 14 cm H2O, tidal volume < 6mL/kg) and b) individualized mechanical ventilation: 10 rats received 150 minutes of mechanical ventilation with an individualized driving pressure according to their Young’s modulus. In both groups, an individualized PEEP was programmed in the same manner. We analyzed the concentration of IL-6, TNF – α, and IL -1ß in BAL and the acute lung injury score in lung tissue postmortem. Results: Global driving pressure was different between the groups (14 vs 11 cm H2O, p = 0.03). The individualized mechanical ventilation group had lower concentrations in bronchoalveolar lavage of IL-6 (270 vs 155 pg/mL, p = 0.02), TNF – α (292 vs 139 pg/mL, p < 0.01) and IL – 1ß (563 vs 131 pg/mL, p = 0.05). They presented lower proportion of lymphocytes (96% vs 79%, p = 0.05) as well as lower lung injury score (6.0 vs 2.0, p = 0.02). Conclusion: In our model, individualization of DP to pulmonary elastance through Young’s modulus decreases lung inflammation and structural lung injury without a significant impact on oxygenation.
Synthetic demand flow generation using theproximity factor
Authors: Yalvac Ekin , Kay Michael G
Published: August 2022

One of the biggest challenges in designing a logistics network is predicting thedemand flows between all pairs of points in the network. Until recently, thegravity model was mainly used for estimating the demand flow between points.However, the gravity model uses historical data to estimate values for its multi-ple parameters and distance between pairs to forecast the demand flow. Distancevalues close to zero and unprecedented changes in demand flow data create nu-merical instability for the gravity model’s output. Hence, the proximity factor,a single parameter model that uses the relative ordering of pairs instead of dis-tance, was developed. In this paper, we systematically compare the proximityfactor and the gravity model. It is shown that the proximity factor is a robustand competitive alternative to the gravity model. According to our analysis,the proximity factor model can replace the gravity model in some applicationswhen no historical data is available to adjust the parameters of the latter.
Behavioral and Biologic Characteristics of Cancer-related Cognitive Impairment Biotypes
Authors: Mulholland Michele M. , Prinsloo Sarah , Kvale Elizabeth , Dula Adrienne N. , Palesh Oxana , Kesler Shelli R.
Published: August 2022

Psychiatric diagnosis is moving away from symptom-based classification and towards multi-dimensional, biologically-based characterization, or biotyping. We previously identified three biotypes of chemotherapy-related cognitive impairment based on functional brain connectivity. In this follow-up study, we evaluated additional factors to help explain biotype expression: neurofunctional stability, brain age, apolipoprotein (APOE) genotype, and psychoneurologic symptoms. We also compared the discriminative ability of a traditional, symptom-based cognitive impairment definition with that of biotypes. We found significant differences in cortical brain age (F = 10.86, p < 0.001), neurofunctional stability (F = 2.85, p = 0.040), APOE e4 genotype (X2 = 7.89, p = 0.048), and psychoneurological symptoms (Pillai = 0.339, p < 0.001) across the three biotypes. The more resilient (Biotype 2) demonstrated significantly higher neurofunctional stability compared to the other biotypes. Symptom-based classification of cognitive impairment did not differentiate biologic or other behavioral variables, suggesting that traditional categorization of cancer-related cognitive effects may miss important characteristics which could inform targeted treatment strategies. Additionally, biotyping, but not symptom-typing, was able to distinguish survivors with cognitive versus psychological effects. Our results suggest that Biotype 1 survivors might benefit from first addressing symptoms of anxiety and fatigue, Biotype 3 might benefit from a treatment plan which includes sleep hygiene, and Biotype 2 might benefit most from cognitive skills training or rehabilitation. Future research should include additional demographic and clinical information to further investigate biotype expression related to risk and resilience and examine integration of more clinically feasible imaging approaches.