bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanocarriers for effective delivery: modulation of innate immunity for the management of infections and the associated complications
Authors: Ko Chung-Nga , Zang Shaohong , Zhou Yingtang , Zhong Zhangfeng , Yang Chao
Published: August 2022

Innate immunity is the first line of defense against invading pathogens. Innate immune cells can recognize invading pathogens through recognizing pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). The recognition of PAMPs by PRRs triggers immune defense mechanisms and the secretion of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. However, sustained and overwhelming activation of immune system may disrupt immune homeostasis and contribute to inflammatory disorders. Immunomodulators targeting PRRs may be beneficial to treat infectious diseases and their associated complications. However, therapeutic performances of immunomodulators can be negatively affected by (1) high immune-mediated toxicity, (2) poor solubility and (3) bioactivity loss after long circulation. Recently, nanocarriers have emerged as a very promising tool to overcome these obstacles owning to their unique properties such as sustained circulation, desired bio-distribution, and preferred pharmacokinetic and pharmacodynamic profiles. In this review, we aim to provide an up-to-date overview on the strategies and applications of nanocarrier-assisted innate immune modulation for the management of infections and their associated complications. We first summarize examples of important innate immune modulators. The types of nanomaterials available for drug delivery, as well as their applications for the delivery of immunomodulatory drugs and vaccine adjuvants are also discussed.
Can machine learning models predict maternal and newborn healthcare providers’ perception of safety during the COVID-19 pandemic? A cross-sectional study of a global online survey
Authors: Hammoud Bassel , Semaan Aline , Elhajj Imad , Benova Lenka
Published: August 2022

Background

Maternal and newborn healthcare providers are essential professional groups vulnerable to physical and psychological risks associated with the COVID-19 pandemic. This study uses machine learning algorithms to create a predictive tool for maternal and newborn healthcare providers’ perception of being safe in the workplace globally during the pandemic.

Methods

We used data collected between 24 March and 5 July 2020 through a global online survey of maternal and newborn healthcare providers. The questionnaire was available in 12 languages. To predict healthcare providers’ perception of safety in the workplace, we used features collected in the questionnaire, in addition to publicly available national economic and COVID-19-related factors. We built, trained and tested five machine learning models: Support Vector Machine (SVM), Random Forest (RF), XGBoost, CatBoost and Artificial Neural Network (ANN) for classification and regression. We extracted from RF models the relative contribution of features in output prediction.

Results

Models included data from 941 maternal and newborn healthcare providers from 89 countries. ML models performed well in classification and regression tasks, whereby RF had 82% cross-validated accuracy for classification, and CatBoost with 0.46 cross-validated root mean square error for regression. In both classification and regression, the most important features contributing to output prediction were classified as three themes: (1) information accessibility, clarity and quality; (2) availability of support and means of protection; and (3) COVID-19 epidemiology.

Conclusion

This study identified salient features contributing to maternal and newborn healthcare providers perception of safety in the workplace. The developed tool can be used by health systems globally to allow real-time learning from data collected during a health system shock. By responding in real-time to the needs of healthcare providers, health systems could prevent potential negative consequences on the quality of care offered to women and newborns.
A new nutraceutical (Livogen Plus®) improves liver steatosis in adults with non-alcoholic fatty liver disease
Authors: Ferro Yvelise , Pujia Roberta , Mazza Elisa , Lascala Lidia , Lodari Oscar , Maurotti Samantha , Pujia Arturo , Montalcini Tiziana
Published: August 2022

Background

Currently, there is no approved medication for non-alcoholic fatty liver disease management. Pre-clinical and clinical studies showed that several bioactive molecules in plants or foods (i.e., curcumin complex, bergamot polyphenol fraction, artichoke leaf extract, black seed oil, concentrate fish oil, picroliv root, glutathione, S-adenosyl-l-methionine and other natural ingredients) have been associated with improved fatty liver disease. Starting from these evidences, our purpose was to evaluate the effects of a novel combination of abovementioned nutraceuticals as a treatment for adults with fatty liver disease.

Methods

A total of 140 participants with liver steatosis were enrolled in a randomized, double-blind, placebo controlled clinical trial. The intervention group received six softgel capsules daily of a nutraceutical (namely Livogen Plus®) containing a combination of natural bioactive components for 12 weeks. The control group received six softgel capsules daily of a placebo containing maltodextrin for 12 weeks. The primary outcome measure was the change in liver fat content (CAP score). CAP score, by transient elastography, serum glucose, lipids, transaminases, and cytokines were measured at baseline and after intervention.

Results

After adjustment for confounding variables (i.e., CAP score and triglyceride at baseline, and changes of serum γGT, and vegetable and animal proteins, cholesterol intake at the follow-up), we found a greater CAP score reduction in the nutraceutical group rather than placebo (− 34 ± 5 dB/m vs. − 20 ± 5 dB/m, respectively; p = 0.045). The CAP score reduction (%) was even greater in those with aged 60 or less, low baseline HDL-C, AST reduction as well as in men.

Conclusion

Our results showed that a new combination of bioactive molecules as nutraceutical was safe and effective in reducing liver fat content over 12 weeks in individuals with hepatic steatosis.

Trial registration ISRCTN, ISRCTN70887063. Registered 03 August 2021—retrospectively registered, https://doi.org/10.1186/ISRCTN70887063
Preclinical validation and treatment of volumetric modulated arc therapy based total bone marrow irradiation in Halcyon™ ring gantry linear accelerator
Authors: Shahid Tanweer , Mandal Sourav , Biswal Subhra Snigdha , De Arundhati , Mukherjee Mukti , Roy Chowdhury Sandipan , Chakrapani Anupam , George Kirubha , Bhattacharya Jibak , Soren Prosenjit , Ghosh Tanmoy , Sarkar Biplab , Cozzi Luca
Published: August 2022

Aim

This study aims​ to report preclinical validation, and the first clinical treatment of total bone marrow irradiation (TMI) and total bone marrow and lymph nodal irradiation (TMLI) using Volumetric modulated arc therapy in Halcyon-E ring gantry linear accelerator. Preclinical validation includes simulation, planning, patient-specific QA, and dry run.

Material and method

Four patients, two female and two male, with body weights of 116 kg, 52 kg, 64 kg, and 62 kg; with two with chronic myeloid leukemia, one each with acute lymphoblastic leukemia and acute myeloid leukemia (AML) were simulated and planned for TMI/TMLI. Patients were immobilized with a full-body vacuum bag. Head first supine (HFS) and Feet first supine (FFS) CT scans were acquired from head to knee and knee to toe. Planning target volume (PTV) was created with a uniform margin of 6 mm over the total bone marrow/bone marrow + lymph nodes. HFS and FFS PTVs were optimized independently using 6MV unflatten energy for 12 Gy in 6 fractions. Plans were merged to create the resultant dose distribution using a junction bias dose matching technique. The total number of isocenters was ≤ 10 per CT set, and two to four full arcs were used for each isocenter. A junction dose gradient technique was used for dose feathering between arcs between adjacent isocenters.

Result

Only one female patient diagnosed as AML received the TMLI treatment, while the other three patients dropped out due to clinical complications and comorbidities that developed in the time between simulation and treatment. The result presented has been averaged over all four patients. For PTV, 95% dose was normalised to 95% volume, PTV_V107% receiving 3.3 ± 3.1%. Total lung mean and V12Gy were 1048.6 ± 107.1 cGy and 19.5 ± 12.1%. Maximum lens doses were 489.5 ± 35.5 cGy (left: L) and 497 ± 69.2 cGy (right: R). The mean cardiac and bilateral kidney doses were 921.75 ± 89.2 cGy, 917.9 ± 63.2 cGy (L), and 805.9 ± 9.7 cGy (R). Average Monitor Unit was 7738.25 ± 1056.6. The median number of isocenters was 17(HFS+FFS), average MU/Dose (cGy) ratio per isocenter was 2.28 ± 0.3.

Conclusion

Halcyon-E ring gantry linear accelerator capable of planning and delivering TMI/TMLI.​​
Morphological changes of the tricuspid valve complex in functional tricuspid regurgitation on contrast-enhanced computed tomography
Authors: Uchiyama Hiroki , Tachibana Kazutoshi , Osuda Koichi , Kawaharada Nobuyoshi
Published: August 2022

Background

Whether it is possible to perform morphological evaluation of functional tricuspid regurgitation (FTR) on contrast-enhanced computed tomography (CT) was examined by evaluating the relationships between the parameters measured on contrast-enhanced CT and TR severity on transthoracic echocardiography.

Methods

Fifty patients underwent contrast-enhanced CT. Tricuspid annulus area (TAA), tricuspid annulus circumference (TAC), right ventricular volume (RVV), and the distances between the tips and bases of the papillary muscles were measured on contrast-enhanced CT in diastole and systole. The 50 cases were divided into 34 in the TR ≤ mild group (no TR: 3 cases, trivial TR: 24 cases, mild TR: 7 cases), and 16 in the TR ≥ moderate group (moderate TR: 8 cases, severe TR: 8 cases) using the TR grade measured by transthoracic echocardiography, and then differences between the groups were examined.

Results

Significant differences were found in TAA, TAC, and RVV (p < 0.01) and the distances between the tips of the anterior and posterior papillary muscles (p < 0.05) in both diastole and systole. Since the septal papillary muscle could not be identified in 18 cases (36.0%), only the distance between the anterior and posterior papillary muscles was measurable in all cases. On receiver-operating characteristic (ROC) curve analysis, the areas under the ROC curves (AUCs) of TAA, TAC, and RVV were all > 0.7, and the maximum AUC was 0.925 for dRVV.

Conclusions

TAA, TAC, RVV, and the distance between the tips of the anterior and posterior papillary muscles measured on contrast-enhanced CT were shown to be significantly increased in the TR ≥ moderate group. Detailed morphological assessment of FTR is possible by contrast-enhanced CT.
Delayed sternal closure for intractable bleeding after acute type A aortic dissection repair: outcomes and risk factors analyses
Authors: Lin Chun-Yu , Wu Meng-Yu , Tseng Chi-Nan , Lee Hsin-Fu , Tsai Feng-Chun
Published: August 2022

Background

Perioperative coagulopathy and intractable bleeding are severe complications in acute type A aortic dissection (ATAAD) repair surgery. Mediastinal packing with delayed sternal closure (DSC) is a commonly adapted technique to stabilize the hemorrhagic tendency. This retrospective study aims to investigate the early and late outcomes and risk factors in patients who underwent DSC procedure during ATAAD repair surgery.

Methods

This study investigated 704 consecutive patients who underwent ATAAD repair at this institution between January 2007 and September 2020. These patients were dichotomized into the DSC (n = 109; 15.5%) and primary sternal closure (PSC) groups (n = 595; 84.5%). The clinical features, surgical information, postoperative complications, 5-years cumulative survival, and freedom from reoperation rates were compared. A multivariate logistic regression analysis was used to identify the independent risk factors for patients who underwent DSC.

Results

The DSC group showed a higher rate of hemopericardium and preoperative malperfusion, and was associated with longer cardiopulmonary bypass and aortic clamping times and a higher rate of intraoperative extracorporeal membrane oxygenation (ECMO) support. The DSC group showed higher blood transfusion volumes and rate of reexploration for bleeding after surgery. However, the in-hospital mortality rates (17.4% vs. 13.3%;P = 0.249), 5-year survival rates (66.9% vs. 68.2%;P = 0.635), and freedom from reoperation rates (89.1% vs. 82.5%;P = 0.344) were comparable between the DSC and PSC groups. Multivariate analysis revealed that hemopericardium, preoperative malperfusion, and intraoperative ECMO support were risk factors for implementing DSC.

Conclusions

DSC is an efficient life-saving technique to stabilize patients with intractable bleeding after undergoing ATAAD repair surgery, which leads to acceptable short- and long-term outcomes. Patients who were at risk for intractable bleeding should have early decision-making for implementing DSC.
Tribology of the sock‐skin Interface – the influence of different fabric parameters on sock friction
Authors: DeBois Ian J. , Agarwal Esha , Kapoor Ashish , Mathur Kavita
Published: August 2022

Background

The purpose of this parametric design of experiments was to identify and summarize how the influence of knit structure (single jersey vs. terry), fiber composition (polyester vs. cotton), fiber linear density (30/1 Ne vs. 18/1 Ne & 1/150/34 vs. 2/150/34), and yarn type (filament vs. spun) affected the frictional profile across the sock‐skin interface.

Methods

Friction testing trials were completed against both a polypropylene probe and a synthetic skin material (Lorica soft®) to determine if there was a difference in friction based on interface interaction. Friction testing was completed by sliding a probe across the inside bottom surface of the sock (the part that is usually in‐contact with the bottom of the foot) while instantaneously measuring the frictional force every tenth of a second.

Results

For both trials (plastic probe and synthetic skin), in the dry condition, knit structure was found to be the most prominent fabric parameter affecting the frictional force experienced at the sock‐skin interface. It was also determined that fiber linear density, and yarn type are tertiary factors affecting the frictional force measured at the sock‐skin interface. Finally, in the dry state, it was determined that fiber composition had seemingly no effect on the frictional force experienced at the sock‐skin interface.

Conclusion

This parametric design of experiments has further enhanced the understanding of the tribology at the sock‐skin interface. Through strategic design, four different textile parameters have been investigated, measured, and justified as to how each influence the friction measured between the two interfaces. This knowledge can be used to develop socks that mitigate the risk of friction blisters formation.
Subphenotypes in acute kidney injury: a narrative review
Authors: Vaara Suvi T. , Bhatraju Pavan K. , Stanski Natalja L. , McMahon Blaithin A. , Liu Kathleen , Joannidis Michael , Bagshaw Sean M.
Published: August 2022

Acute kidney injury (AKI) is a frequently encountered syndrome especially among the critically ill. Current diagnosis of AKI is based on acute deterioration of kidney function, indicated by an increase in creatinine and/or reduced urine output. However, this syndromic definition encompasses a wide variety of distinct clinical features, varying pathophysiology, etiology and risk factors, and finally very different short- and long-term outcomes. Lumping all AKI together may conceal unique pathophysiologic processes specific to certain AKI populations, and discovering these AKI subphenotypes might help to develop targeted therapies tackling unique pathophysiological processes. In this review, we discuss the concept of AKI subphenotypes, current knowledge regarding both clinical and biomarker-driven subphenotypes, interplay with AKI subphenotypes and other ICU syndromes, and potential future and clinical implications.
EvaLuation of early CRRT and beta-blocker InTervention in patients with ECMO (ELITE) trial: study protocol for a 2 × 2 partial factorial randomized controlled trial
Authors: Wang Xiaofang , Wang Hong , Du Xin , Wang Zhiyan , Li Chenglong , Anderson Craig S. , Zhang Jinying , Hou Xiaotong , Dong Jianzeng
Published: August 2022

Background

In critically ill patients requiring extracorporeal membrane oxygenation (ECMO) therapy, early initiation of continuous renal replacement therapy (CRRT) and beta-blockade of catecholamine-induced inotropic effects may improve outcomes.

Methods

A 2 × 2 partial factorial randomized controlled trial in eligible ECMO patients without a clear indication or contraindication to either intervention is centrally randomly assigned to (A) early or conventional-indicated CRRT and/or (B) beta-blocker or usual care. The primary outcome is all-cause mortality at 30 days for both arms. A total of 496 participants provides 80% power to determine a 20% risk reduction in mortality at 30 days with 5% type I error.

Discussion

This trial will help define the role of early CRRT and beta-blockade in ECMO patients. There have been 89 patients enrolled at 10 hospitals in study A and is ongoing. However, study B was stopped in August 2019 in the absence of any patients being enrolled.

Trial registration

ClinicalTrials.govNCT03549923. Registered on 8 June 2018. World Health Organization International Clinical Trials Registry Platform (WHO ICTEP) network. The Ethics Committee of Beijing Anzhen Hospital Approval ID is 2018013.
Application of green first derivative synchronous spectrofluorometric method for quantitative analysis of fexofenadine hydrochloride and pseudoephedrine hydrochloride in pharmaceutical preparation and spiked human plasma
Authors: Ramzy Sherif , Abdelazim Ahmed H. , Hasan Mohamed A.
Published: August 2022

Fexofenadine hydrochloride and pseudoephedrine hydrochloride are prescribed in a combined dosage form for the treatment of allergic rhinitis. In the present work, a sensitive synchronous fluorescence spectroscopic method was applied in conjunction with first derivative for quantitative estimation of fexofenadine hydrochloride and pseudoephedrine hydrochloride in pure form, pharmaceutical tablets and spiked human plasma. Fexofenadine hydrochloride showed its conventional emission spectrum at 294 nm when excited at 267 nm. On the other hand, pseudoephedrine hydrochloride showed its conventional emission spectra at 286 nm when excited at 261 nm. The fluorescence intensities were greatly enhanced by the use of sodium dodecyl sulphate as a micellar surfactant. Application of the synchronous mode to measure the fluorescence spectra of the above drugs provided sharp narrowing bands, but the overlap was not completely resolved. Derivatization of the synchronous spectra to the first order completely resolved the overlap of the fluorescence spectra and allowed simultaneous quantitative determination of the drugs under study. Fexofenadine hydrochloride and pseudoephedrine hydrochloride could be determined from their first-order synchronous spectra at 286 and 294 nm, respectively, without interfering with each other. The method showed linearity with an excellent correlation coefficient in the concentration range of 100–1500 ng/mL for Fexofenadine hydrochloride and 50–1000 ng/mL for pseudoephedrine hydrochloride. The method was successfully applied for the simultaneous determination of the studied drugs in pharmaceutical formulation, with mean percent recoveries for Fexofenadine hydrochloride and pseudoephedrine hydrochloride of 99.49 ± 0.931 and 98.67 ± 0.634, respectively, and in spiked human plasma, with mean percent recoveries for Fexofenadine hydrochloride and pseudoephedrine hydrochloride of 95.21 ± 1.938 and 94.89 ± 1.763, respectively. Furthermore, the greenness of the described method was assessed using four different tools namely, the national environmental method index, the analytical eco-scale, the green analytical procedure index and the AGREE evaluation method. The proposed method seemed to be superior to the reported HPLC method with respect to the metrics of the greenness characters.
PDS5A and PDS5B differentially affect gene expression without altering cohesin localization across the genome
Authors: Arruda Nicole L. , Bryan Audra F. , Dowen Jill M.
Published: August 2022

Background

Cohesin is an important structural regulator of the genome, regulating both three-dimensional genome organization and gene expression. The core cohesin trimer interacts with various HEAT repeat accessory subunits, yielding cohesin complexes of distinct compositions and potentially distinct functions. The roles of the two mutually exclusive HEAT repeat subunits PDS5A and PDS5B are not well understood.

Results

Here, we determine that PDS5A and PDS5B have highly similar localization patterns across the mouse embryonic stem cell (mESC) genome and they show a strong overlap with other cohesin HEAT repeat accessory subunits, STAG1 and STAG2. Using CRISPR/Cas9 genome editing to generate individual stable knockout lines for PDS5A and PDS5B, we find that loss of one PDS5 subunit does not alter the distribution of the other PDS5 subunit, nor the core cohesin complex. Both PDS5A and PDS5B are required for proper gene expression, yet they display only partially overlapping effects on gene targets. Remarkably, gene expression following dual depletion of the PDS5 HEAT repeat proteins does not completely overlap the gene expression changes caused by dual depletion of the STAG HEAT repeat proteins, despite the overlapping genomic distribution of all four proteins. Furthermore, dual loss of PDS5A and PDS5B decreases cohesin association with NIPBL and WAPL, reduces SMC3 acetylation, and does not alter overall levels of cohesin on the genome.

Conclusions

This work reveals the importance of PDS5A and PDS5B for proper cohesin function. Loss of either subunit has little effect on cohesin localization across the genome yet PDS5A and PDS5B are differentially required for gene expression.
Multiple horizontal transfers of a Helitron transposon associated with a parasitoid wasp
Authors: Heringer Pedro , Kuhn Gustavo C. S.
Published: August 2022

In a previous study we described a Helitron transposon that apparently became one of the segments in the symbiotic Cotesia vestalis bracovirus (CvBV) from the parasitoid wasp C. vestalis. We presented evidence that this Helitron, named Hel_c35, invaded the C. vestalis genome through a horizontal transfer (HT) event from a dipteran and was later transferred horizontally from C. vestalis to a lepidopteran species. Based on the phylogeny of Hel_c35, we suggested that both HTs occurred in East Asia. We have also anticipated that, as more sequenced genomes from new species become available, more HTs involving Hel_c35 would be detected. Although the inclusion of Hel_c35 as a CvBV segment turned out to be a methodological artifact, the fact that Hel_c35 copies are present in the genomes of C. vestalis and other arthropods still remains. Here, we investigated the evolution of Hel_c35 in arthropods using an updated data set to reassess our previous findings. Most species (95%) included in the present work had their genomes sequenced after our initial study was published, thus representing new descriptions of taxa harboring Hel_c35. Our results expand considerably the number of putative HTs involving Hel_c35, with up to dozens of previously undescribed events, and suggest that the most recent HTs associated with C. vestalis took place in Europe. Considering the phylogenetic distribution of Hel_c35, and the evidence that its DNA sequences are present in the calyx fluid of C. vestalis and tissues from its parasitized host, we argue that many HT events were favored by the behavior of this wasp.
Diabetic microenvironment preconditioning of adipose tissue-derived mesenchymal stem cells enhances their anti-diabetic, anti-long-term complications, and anti-inflammatory effects in type 2 diabetic rats
Authors: Su Wanlu , Yu Songyan , Yin Yaqi , Li Bing , Xue Jing , Wang Jie , Gu Yulin , Zhang Haixia , Lyu Zhaohui , Mu Yiming , Cheng Yu
Published: August 2022

Background

Mesenchymal stem cells (MSCs) exert anti-diabetic effects and improve long-term complications via secretory effects that regulate macrophage polarisation and attenuate inflammation. Enhancing the efficacy of MSCs needs to be explored further. The in vitro culture microenvironment influences the secretory profile of MSCs. Therefore, we hypothesised that a diabetic microenvironment would promote the secretion of cytokines responsible for macrophage polarisation, further attenuating systemic inflammation and enhancing the effects of MSCs on type 2 diabetes (T2D) and long-term diabetic complications.

Methods

Preconditioned adipose-derived mesenchymal stem cells (pre-ADSCs) were obtained after co-cultivating ADSCs in a diabetic metabolic environment (including high sugar, advanced glycation end-product, and lipopolysaccharides). The regulatory effects of pre-ADSCs on macrophages were observed in vitro. A T2D rat model was induced with a high-fat diet for 32 weeks combined with an intraperitoneal injection of streptozotocin. Sprague–Dawley (SD) rats were divided into four groups: normal group, diabetes without treatment group (PBS), ADSC treatment group, and pre-ADSC treatment group. ADSCs and pre-ADSCs were intravenously administered weekly to SD rats for 6 months, and then glucose homeostasis and long-term diabetic complications were evaluated in each group.

Results

The secretion of cytokines related to M2 macrophage polarisation (IL-6, MCP-1, etc.) was increased in the pre-ADSC group in the in vitro model. Pre-ADSC treatment significantly maintained blood glucose homeostasis, reduced insulin resistance, promoted islet regeneration, and ameliorated the complications related to diabetes in rats (chronic kidney disease, non-alcoholic steatohepatitis, lung fibrosis, and cataract) compared to the ADSC group (P < 0.05). Additionally, the number of anti-inflammatory M2 macrophage phenotypes was enhanced in tissues following pre-ADSC injections. Moreover, the expression of pro-inflammatory genes (iNOS, TNF-α, IL-1β) was reduced whereas that of anti-inflammatory genes (Arg1, CD206, and Il-10) was increased after cultivation with pre-ADSCs.

Conclusion

Diabetic microenvironment-preconditioned ADSCs effectively strengthen the capacity against inflammation and modulate the progress of long-term T2D complications.
Aucubin promotes bone-fracture healing via the dual effects of anti-oxidative damage and enhancing osteoblastogenesis of hBM-MSCs
Authors: Wang Kanbin , Zhou Chengwei , Li Lijun , Dai Chengxin , Wang Zhongxiang , Zhang Weijun , Xu Jianxiang , Zhu Yueliang , Pan Zhijun
Published: August 2022

Background

Aucubin (AU), an iridoid glucoside isolated from many traditional herbal medicines, has anti-osteoporosis and anti-apoptosis bioactivities. However, the effect of AU on the treatment of bone-fracture remains unknown. In the present study, the aims were to investigate the roles and mechanisms of AU not only on osteoblastogenesis of human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) and anti-oxidative stress injury in vitro, but also on bone-fracture regeneration by a rat tibial fracture model in vivo.

Methods

CCK-8 assay was used to assess the effect of AU on the viability and proliferation of hBM-MSCs. The expression of specific genes and proteins on osteogenesis, apoptosis and signaling pathways was measured by qRT-PCR, western blotting and immunofluorescence analysis. ALP staining and quantitative analysis were performed to evaluate ALP activity. ARS and quantitative analysis were performed to evaluate calcium deposition. DCFH-DA staining was used to assess the level of reactive oxygen species (ROS). A rat tibial fracture model was established to validate the therapeutic effect of AU in vivo. Micro-CT with quantitative analysis and histological evaluation were used to assess the therapeutic effect of AU locally injection at the fracture site.

Results

Our results revealed that AU did not affect the viability and proliferation of hBM-MSCs. Compared with control group, western blotting, PCR, ALP activity and calcium deposition proved that AU-treated groups promoted osteogenesis of hBM-MSCs. The ratio of phospho-Smad1/5/9 to total Smad also significantly increased after treatment of AU. AU-induced expression of BMP2 signaling target genes BMP2 and p-Smad1/5/9 as well as of osteogenic markers COL1A1 and RUNX2 was downregulated after treating with noggin and LDN193189. Furthermore, AU promoted the translocation of Nrf2 from cytoplasm to nucleus and the expression level of HO1 and NQO1 after oxidative damage. In a rat tibial fracture model, local injection of AU promoted bone regeneration.

Conclusions

Our study demonstrates the dual effects of AU in not only promoting bone-fracture healing by regulating osteogenesis of hBM-MSCs partly via canonical BMP2/Smads signaling pathway but also suppressing oxidative stress damage partly via Nrf2/HO1 signaling pathway.
Probabilistic volcanic hazard assessment at an active but under-monitored volcano: Ceboruco, Mexico
Authors: Constantinescu Robert , González-Zuccolotto Karime , Ferrés Dolors , Sieron Katrin , Siebe Claus , Connor Charles , Capra Lucia , Tonini Roberto
Published: August 2022

A probabilistic volcanic hazard assessment (PVHA) for Ceboruco volcano (Mexico) is reported using PyBetVH, an e-tool based on the Bayesian Event Tree (BET) methodology. Like many volcanoes, Ceboruco is under-monitored. Despite several eruptions in the late Holocene and efforts by several university and government groups to create and sustain a monitoring network, this active volcano is monitored intermittently rather than continuously by dedicated groups. With no consistent monitoring data available, we look at the geology and the eruptive history to inform prior models used in the PVHA. We estimate the probability of a magmatic eruption within the next time window (1 year) of ~ 0.002. We show how the BET creates higher probabilities in the absence of monitoring data, which if available would better inform the prior distribution. That is, there is a cost in terms of higher probabilities and higher uncertainties for having not yet developed a sustained volcano monitoring network. Next, three scenarios are developed for magmatic eruptions:i)small magnitude (effusive/explosive), ii)medium magnitude (Vulcanian/sub-Plinian) andiii)large magnitude (Plinian). These scenarios are inferred from the Holocene history of the volcano, with their related hazardous phenomena: ballistics, tephra fallout, pyroclastic density currents, lahars and lava flows. We present absolute probability maps (unconditional in terms of eruption size and vent location) for a magmatic eruption at Ceboruco volcano. With PyBetVH we estimate and visualize the uncertainties associated with each probability map. Our intent is that probability maps and uncertainties will be useful to local authorities who need to understand the hazard when considering the development of long-term urban and land-use planning and short-term crisis management strategies, and to the scientific community in their efforts to sustain monitoring of this active volcano.
A network business availability modeling method based on Markov chain
Authors: Lu Ying , Chen Yusi , Liu Jin , Fu Yanfang , Guo Qi , Fan Nierui
Published: August 2022

Military tactical networks (MTNs) have grown in size and complexity as the volume of battlefield communications business has increased dramatically. There is a critical need for a quantitative evaluation method to assess the performance of MTNs. Based on the transmission characters of battlefield communication business and the availability of communication equipment, this paper proposed a Markov chain-based network steady-state availability model. Using this model and the analysis of the CSMA/CA transmission protocol as preconditions, a delay-based quantitative evaluation model of network business availability is proposed based on statistical principles. The relationship between network business availability and crucial metrics such as node size and node failure/repair ratio is investigated in simulation experiments to ensure the validity and correctness of the proposed model. The work done in this paper contributes to effectively evaluating the overall availability of MTNs in a complex environment.
Association between treatment setting and outcomes among oregon medicaid patients with opioid use disorder: a retrospective cohort study
Authors: Hartung Daniel M. , Markwardt Sheila , Johnston Kirbee , Geddes Jonah , Baker Robin , Leichtling Gillian , Hildebran Christi , Chan Brian , Cook Ryan R. , McCarty Dennis , Ghitza Udi , Korthuis P. Todd
Published: August 2022

Background

Residential treatment is a common approach for treating opioid use disorder (OUD), however, few studies have directly compared it to outpatient treatment. The objective of this study was to compare OUD outcomes among individuals receiving residential and outpatient treatment.

Methods

A retrospective cohort study used linked data from a state Medicaid program, vital statistics, and the Substance Abuse and Mental Health Services Administration (SAMHSA) Treatment Episodes Dataset (TEDS) to compare OUD-related health outcomes among individuals treated in a residential or outpatient setting between 2014 and 2017. Multivariable Cox proportional hazards and logistic regression models examined the association between treatment setting and outcomes (i.e., opioid overdose, non-overdose opioid-related and all-cause emergency department (ED) visits, hospital admissions, and treatment retention) controlling for patient characteristics, co-morbidities, and use of medications for opioid use disorders (MOUD). Interaction models evaluated how MOUD use modified associations between treatment setting and outcomes.

Results

Of 3293 individuals treated for OUD, 957 (29%) received treatment in a residential facility. MOUD use was higher among those treated as an outpatient (43%) compared to residential (19%). The risk of opioid overdose (aHR 1.39; 95% CI 0.73–2.64) or an opioid-related emergency department encounter or admission (aHR 1.02; 95% CI 0.80–1.29) did not differ between treatment settings. Independent of setting, MOUD use was associated with a significant reduction in overdose risk (aHR 0.45; 95% CI 0.23–0.89). Residential care was associated with greater odds of retention at 6-months (aOR 1.71; 95% CI 1.32–2.21) but not 1-year. Residential treatment was only associated with improved retention for individuals not receiving MOUD (6-month aOR 2.05; 95% CI 1.56–2.71) with no benefit observed in those who received MOUD (aOR 0.75; 95% CI 0.46–1.29; interaction p = 0.001).

Conclusions

Relative to outpatient treatment, residential treatment was not associated with reductions in opioid overdose or opioid-related ED encounters/hospitalizations. Regardless of setting, MOUD use was associated with a significant reduction in opioid overdose risk.
The measurement-based care to opioid treatment programs project (MBC2OTP): a study protocol using rapid assessment procedure informed clinical ethnography
Authors: Scott Kelli , Guigayoma John , Palinkas Lawrence A. , Beaudoin Francesca L. , Clark Melissa A. , Becker Sara J.
Published: August 2022

Background

Psychosocial interventions are needed to enhance patient engagement and retention in medication treatment within opioid treatment programs. Measurement-based care (MBC), an evidence-based intervention structure that involves ongoing monitoring of treatment progress over time to assess the need for treatment modifications, has been recommended as a flexible and low-cost intervention for opioid treatment program use. The MBC2OTP Project is a two-phase pilot hybrid type 1 effectiveness-implementation trial that has three specific aims: (1) to employ Rapid Assessment Procedure Informed Clinical Ethnography (RAPICE) to collect mixed methods data to inform MBC implementation; (2) to use RAPICE data to adapt an MBC protocol; and (3) to conduct a hybrid type 1 trial to evaluate MBC’s preliminary effectiveness and implementation potential in opioid treatment programs.

Methods

This study will be conducted in two phases. Phase 1 will include RAPICE site visits, qualitative interviews (N = 32–48 total), and quantitative surveys (N = 64–80 total) with staff at eight programs to build community partnerships and evaluate contextual factors impacting MBC implementation. Mixed methods data will be analyzed using immersion/crystallization and thematic analysis to inform MBC adaptation and site selection. Four programs selected for Phase 2 will participate in MBC electronic medical record integration, training, and ongoing support. Chart reviews will be completed in the 6 months prior-to and following MBC integration (N = 160 charts, 80 pre and post) to evaluate effectiveness (patient opioid abstinence and treatment engagement) and implementation outcomes (counselor MBC exposure and fidelity).

Discussion

This study is among the first to take forward recommendations to implement and evaluate MBC in opioid treatment programs. It will also employ an innovative RAPICE approach to enhance the quality and rigor of data collection and inform the development of an MBC protocol best matched to opioid treatment programs. Overall, this work seeks to enhance treatment provision and clinical outcomes for patients with opioid use disorder.

Trial registration This study will be registered with Clinicaltrials.gov within 21 days of first participant enrollment in Phase 2. Study Phase 1 (RAPICE) does not qualify as a clinical trial, therefore Phase 2 clinical trial registration has not yet been pursued because all elements of Phase 2 will be dependent on Phase 1 outcomes.
The association between serum lipid levels and histological type of breast cancer
Authors: Wang Xinru , Wang Yajie , Wang Miaomiao , Chen Xin , Cui Wenjing , Chen Xiao
Published: August 2022

Background

Studies have investigated the association between serum lipids level or apolipoprotein levels and breast cancer (BC) risk. However, the relationship between serum lipids level and apolipoprotein levels and histological type of breast cancer remains unclear. This study was aimed to explore the association between serum lipids level and the histological type of BC, particularly to estrogen receptor (ER) and progesterone receptor (PR) positive BC.

Materials and methods

220 cases of pathology-confirmed BC were retrospectively collected in this study. Patients’ demographic information, clinical data, and pathological features were obtained from medical records. Serum levels including high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), total cholesterol (TC), triglyceride (TG), apolipoprotein A (ApoA), ApoB, ApoE and lipoprotein a(LP(a)) were collected before treatment. Logistic regression analyses were used to show the association between serum lipids and subtypes of BC. Receiver operating characteristic (ROC) curves were generated to analyze the predictive performance.

Results

There were 70 ER-negative and 73 PR-negative BC. Patients with ER-negative BC had higher HDL-c, higher LDL-c, and higher LP(a) than those in ER-positive one (p < 0.05). Patients with PR-negative BC were more likely to have high LDL-c and high LP(a) levels than patients with PR-positive one (p < 0.05). Multivariate logistic regression analysis showed that serum HDL-c (odds ratio (OR): 0.27, 95% confidence interval (CI) 0.10–0.76), LDL-c (OR: 0.19, 95%CI 0.04–0.93) and LP(a) (OR: 0.23,95%CI 0.07–0.80) levels were negatively associated with ER-positive BC, and serum HDL-c and LDL-c levels were significantly negatively associated with PR-positive BC (OR: 0.32, 95%CI 0.12–0.82; OR: 0.14, 95%CI 0.03–0.77). In addition, ER and PR positive BC was negatively associated with serum HDL-c and LDL-c levels (OR = 0.39, 95% CI 0.17–0.91; OR = 0.22, 95% CI 0.06–0.85) after adjusting with confounders. Serum HDL-c level (OR = 0.13, 95% CI 0.02–0.87) was still independently associated with ER and PR positive BC in postmenopausal women. The area under the curves (AUCs) of HDL-c to identify ER-positive BC, PR-positive BC, and ER and PR positive BC were 0.65 (95%CI 0.58–0.73, P < 0.01), 0.62 (95%CI 0.54–0.69, P < 0.01) and 0.64 (95%CI 0.56–0.72, P < 0.01), respectively.

Conclusions

Serum HDL-c and LDL-c levels were related to ER or PR positive BC. Lipid levels may also have acceptable performance in identifying BC histological type.
Colistin-degrading proteases confer collective resistance to microbial communities during polymicrobial infections
Authors: Lee Do-Hoon , Cha Ju-Hee , Kim Dae-Wi , Lee Kihyun , Kim Yong-Seok , Oh Hyo-Young , Cho You-Hee , Cha Chang-Jun
Published: August 2022

Background

The increasing prevalence of resistance against the last-resort antibiotic colistin is a significant threat to global public health. Here, we discovered a novel colistin resistance mechanism via enzymatic inactivation of the drug and proposed its clinical importance in microbial communities during polymicrobial infections.

Results

A bacterial strain of the Gram-negative opportunistic pathogen Stenotrophomonas maltophilia capable of degrading colistin and exhibiting a high-level colistin resistance was isolated from the soil environment. A colistin-degrading protease (Cdp) was identified in this strain, and its contribution to colistin resistance was demonstrated by growth inhibition experiments using knock-out (Δcdp) and complemented (Δcdp::cdp) mutants. Coculture and coinfection experiments revealed that S. maltophilia carrying the cdp gene could inactivate colistin and protect otherwise susceptible Pseudomonas aeruginosa, which may seriously affect the clinical efficacy of the drug for the treatment of cystic fibrosis patients with polymicrobial infection.

Conclusions

Our results suggest that Cdp should be recognized as a colistin resistance determinant that confers collective resistance at the microbial community level. Our study will provide vital information for successful clinical outcomes during the treatment of complex polymicrobial infections, particularly including S. maltophilia and other colistin-susceptible Gram-negative pathogens such as P. aeruginosa.
A comprehensive evaluation of microbial differential abundance analysis methods: current status and potential solutions
Authors: Yang Lu , Chen Jun
Published: August 2022

Background

Differential abundance analysis (DAA) is one central statistical task in microbiome data analysis. A robust and powerful DAA tool can help identify highly confident microbial candidates for further biological validation. Numerous DAA tools have been proposed in the past decade addressing the special characteristics of microbiome data such as zero inflation and compositional effects. Disturbingly, different DAA tools could sometimes produce quite discordant results, opening to the possibility of cherry-picking the tool in favor of one’s own hypothesis. To recommend the best DAA tool or practice to the field, a comprehensive evaluation, which covers as many biologically relevant scenarios as possible, is critically needed.

Results

We performed by far the most comprehensive evaluation of existing DAA tools using real data-based simulations. We found that DAA methods explicitly addressing compositional effects such as ANCOM-BC, Aldex2, metagenomeSeq (fitFeatureModel), and DACOMP did have improved performance in false-positive control. But they are still not optimal: type 1 error inflation or low statistical power has been observed in many settings. The recent LDM method generally had the best power, but its false-positive control in the presence of strong compositional effects was not satisfactory. Overall, none of the evaluated methods is simultaneously robust, powerful, and flexible, which makes the selection of the best DAA tool difficult. To meet the analysis needs, we designed an optimized procedure, ZicoSeq, drawing on the strength of the existing DAA methods. We show that ZicoSeq generally controlled for false positives across settings, and the power was among the highest. Application of DAA methods to a large collection of real datasets revealed a similar pattern observed in simulation studies.

Conclusions

Based on the benchmarking study, we conclude that none of the existing DAA methods evaluated can be applied blindly to any real microbiome dataset. The applicability of an existing DAA method depends on specific settings, which are usually unknown a priori. To circumvent the difficulty of selecting the best DAA tool in practice, we design ZicoSeq, which addresses the major challenges in DAA and remedies the drawbacks of existing DAA methods. ZicoSeq can be applied to microbiome datasets from diverse settings and is a useful DAA tool for robust microbiome biomarker discovery.
Colon cancer with extensive invasion of the abdominal wall treated with neoadjuvant chemotherapy and a free anterolateral thigh flap
Authors: Aritake Tsukasa , Ouchi Akira , Komori Koji , Kinoshita Takashi , Sato Yusuke , Nakamura Ryota , Takanari Keisuke , Taniguchi Hiroya , Muro Kei , Kato Seiichi , Abe Tetsuya , Ito Seiji , Shimizu Yasuhiro
Published: August 2022

Background

The treatment of locally advanced colon cancer is challenging, particularly when there is invasion of the abdominal wall. In such cases, balancing the securing of margins and sufficiently repairing abdominal wall defects is important, but difficult when the extent of invasion is large.

Case presentation

A 34-year-old male was referred to our hospital with abdominal pain and diagnosed with obstructive transverse colon cancer. He had undergone ileo-sigmoid colostomy at his previous hospital. The tumor was massive and invaded the abdominal wall (maximum diameter: approximately 12 cm), and was accompanied by regional lymph node swelling. No distant metastasis was detected. We diagnosed the tumor as cT4bN2bM0 Stage IIIC locally advanced transverse colon cancer and planned neoadjuvant chemotherapy. After two courses of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan), he developed an entero-cutaneous fistula due to tumor penetration and required emergency diverting ileostomy construction. After the procedure, contrast-enhanced computed tomography showed good tumor shrinkage. As a result, the planned chemotherapy was canceled and he underwent radical resection of the tumor. En bloc extended right hemicolectomy was performed with excision of the fistula, ensuring a sufficient margin. The post-excision defect at the anterior abdominal wall involved 11 × 16 cm of fascia and 6 × 9 cm of skin located in the middle of the abdomen. A free anterolateral thigh flap was harvested from the right thigh and vascular pedicle was anastomosed to the right gastroepiploic artery and vein. The fascia lata, which was included in the anterolateral thigh flap, was sutured onto the abdominal wall fascia as inlay fashion to reconstruct the abdominal wall defect. Histopathology revealed moderately differentiated adenocarcinoma of the colon with no tumor cells in the abdominal wall tissue [post-chemotherapeutic state, therapy effect: Grade 1b; Stage IIA (ypT3N0M0)]. All resected margins of the specimen were free from adenocarcinoma. He was discharged on postoperative day 16.

Conclusion

We report a case of colon cancer extensively invading the abdominal wall, which was completely resected. The abdominal wall defect was reconstructed with a free anterolateral thigh flap after tumor shrinkage with neoadjuvant chemotherapy. We present an efficient strategy for managing locally advanced colon cancer with extensive abdominal wall invasion.