bluuebunny/crossref_metadata_2025 huggingface dataset:
Autologous Platelet Lysate Could Have Role in Enhancing the Fracture Healing in Rabbits
Authors: Meftahpour Vafa , Ghorbani Farzaneh , Ahmadi Majid , Aghebati-Maleki Ali , Fotouhi Ali , Zamani Majid , Maleki Arash , Khakpour Mansour , Aghebati-Maleki leili
Published: May 2021

Although bone substitutes supplemented with platelet derived products are widely used in bone regeneration, the role of Platelet lysate needs to be further elucidate in treatment of bone damages. Accordingly, the aim of this animal study was to evaluate the benefits of autologous PL (APL) in fracture healing. Rabbit APL obtained from freeze-thawed platelet suspension and used for treatment of femoral bone damage in 20 rabbits after surgery procedure. Twenty other rabbits with femoral bone damage were assigned to control group which received Phosphate-buffered saline as therapy. ELISA and real-time PCR used for investigation of the secretion and mRNA expression of IL-1, IL‐6, TNF‐α and TGF‐β cytokines, respectively. The mRNA expression of several other related genes including MMP-3, MMP-13, IGF, FGF, VEGF and PDGF was also evaluated in days 0, 15, 30 and 60 which was higher in APL-treated rabbits than that of controls. However, secretion of pro-inflammatory cytokines was meaningfully lower than the control group and reduced significantly after two weeks. These observations indicated that factors released from PL and regulation between them could result in bone fracture healing.
Environmental Enrichment Protects Against Cognition Deficits Caused by Sepsis-Associated Encephalopathy
Authors: Jiang Shan , Zhao Lin , Tang Yi-Fei , Lu Xi , Guo Dan
Published: May 2021

Background: Sepsis-associated encephalopathy (SAE) is a common complication of sepsis and characterized by impaired cognition ability in survivors. Previous studies revealed that environmental enrichment (EE) ameliorated the cognition deficits in different models of brain injury. However, little research exists exploring the effect of EE on SAE. Methods: our present study was designed to determine the possible benefits of EE in ameliorating the cognition deficits following SAE. To examine the benefits of EE, adult male rats with SAE were placed in an enriched environment or standard environment(SE) for 30 days. After the EE or SE housing, the rats were subjected to a behavioral test battery including sensory neglect test (SN), Elevated Plus Maze test (EPM), Open Field test (OF) Morris water maze test (MWM), and Novel Object Recognition test (NOR). Results: Our results showed that SAE-induced the impairment of recognition memory (NOR) and spatial learning and memory (MWM) was significantly inhibited in EE exposed rats. In addition, EE exposure also decreased the SAE-induced anxiety-like behavior (EPM) and increased exploratory activity (OF). However, no difference in locomotion ability was detected between the EE and SE exposed rats. Conclusions: Our results demonstrate the positive effect of EE on cognitive impairments after SAE. These results highlight the importance of environmental enrichment to prevent cognitive deficits induced by SAE.
Glutaric Acidemia type 1 with Atypical Acylcarnitine Profile During Newborn Screening
Authors: Lin Yiming , Wang Wenjun , Lin Chunmei , Zheng Zhenzhu , Fu Qingliu , Peng Weilin , Chen Dongmei
Published: May 2021

Background and aims Glutaric acidemia type 1 (GA1) is a treatable disorder of cerebral organic acid metabolism caused by a defective glutaryl-CoA dehydrogenase (GCDH) gene. There is scarcity of reports of GA1 diagnoses following newborn screening (NBS) in the Chinese population. We assessed the acylcarnitine profiles and genetic characteristics of patients with GA1 identified via NBS.Materials and methods From January 2014 to September 2020, a total of 517,484 newborns screened by tandem mass spectrometry were recruited for this study. Newborns with elevated isovalerylcarnitine (C5DC) levels were recalled, those who tested positive on second screen were referred for confirmatory tests.Results Of 517,484 screened newborns, thirteen patients were diagnosed with GA1, including eleven neonatal GA1 and two maternal GA1 patients. The incidence of GA1 in the Quanzhou region was estimated to be 1 in 47,044 newborns. The initial NBS results showed that all but one of the patients had moderately or markedly increased C5DC levels. The neonatal GA1 patient with low free carnitine (C0) level suggestive of primary carnitine deficiency (PCD) while just the contrary to a typical GA1. Nine neonatal GA1 patients underwent urinary organic acid analyses: eight had elevated GA levels and one was reported in the normal range. Ten distinct GCDH variants were identified, eight were previously reported and two were newly identified. In silico prediction tools and protein modelling analysis suggested that the newly identified variants were potentially pathogenic. The most common variant was c.1244-2A > C, which had an allelic frequency of 54.55% (12/22), followed by c.1261G > A (p.Ala421Thr) (9.09%, 2/22). Conclusions GA1 patients may show only with low C0 levels at the initial screening and recall stages that may be overlooked. Maternal GA1 patients can also be detected during NBS duo to the low C0 levels in their infants. Therefore, PCD should be included in the differential diagnosis for GA1, and multigene panel testing should be performed in newborns with low C0 levels.
Particulate Matter of Different Sizes Associated With Acute Lower Respiratory Infection Outpatient Visits in Children: A Time-Series Analysis in Guangzhou, China
Authors: Liang Zhenyu , Meng Qiong , Yang Qiaohuan , Chen Na , You Chuming
Published: May 2021

Background

The burden of lower respiratory infection is primarily borne by developing countries. However, the association between particulate matter of different sizes and acute lower respiratory infection (ALRI) outpatient visits in developing countries is less studied.
Methods

We obtained data on ALRI outpatient visits (N = 105,639) from a tertiary hospital in Guangzhou, China between 2013 and 2019. Over-dispersed generalized additive Poisson models were employed to evaluate the excess risk (ER) associated with particulate matter [inhalable particulate matter (PM10), coarse particulate matter (PMc), and fine particulate matter (PM2.5)]. Counterfactual analyses were used to examine the potential percent reduction of ALRI outpatient visits if the levels of air pollution were as low as those recommended by the World Health Organization (WHO).
Results

There were 35,310 pneumonia, 68,218 bronchiolitis, and 2,111 asthma outpatient visits included. Each 10 µg/m3 increase of three-day moving averages of particulate matter was associated with significant ER [95% confidence interval (CI)] of outpatient visits of pneumonia [PM2.5: 3.71% (2.91%, 4.52%); PMc: 9.19% (6.94%, 11.49%); PM10: 4.36% (3.21%, 5.52%)], bronchiolitis [PM2.5: 3.21% (2.49%, 3.93%); PMc: 9.13% (7.09%, 11.21%); PM10: 3.12% (2.10%, 4.15%)], and asthma [PM2.5: 3.45% (1.18%, 5.78%); PMc: 11.69% (4.45%, 19.43%); PM10: 3.33% (0.26%, 6.49%)]. The association between particulate matter and pneumonia outpatient visits was stronger among male patients and in cold seasons. Counterfactual analyses suggested that PM2.5 was associated with the largest potential decline of ALRI outpatient visits [pneumonia: 3.89%, 95% CI: (3.24%, 5.52%); bronchiolitis: 4.35% (3.06%, 4.82%); asthma: 5.98% (1.92%, 10.37%)] if the air pollutants were reduced to the level of the reference guidelines.
Conclusion

Short-term exposure to PM2.5, PMc, and PM10 is associated with significant risk of ALRI outpatient visits, among which PM2.5 is associated with the highest potential decline in outpatient visits if it could be reduced to the WHO recommended level.
Genome-Wide Identification and Expression Analysis of Glycosyltransferase Gene Family 1 in Quercus Robur L.
Authors: Zhang Jie , Lin Li-Mei , Cheng Wen-Wen , Xin-Song  , Long Yue-Hong ,   Zhao-Bin Xing1
Published: May 2021

Glycosyltransferase gene family 1, also known as uridine diphosphate glycosyltransferase (UGT), is the largest glycosyltransferase family in plants, playing a vital role in their growth and development. In this study, 244 UGT genes with conserved PSPG motifs were identified in the genome of Quercus robur L. The collinearity analysis results showed that tandem repeat was the main way of UGT genes expansion in Q.robur, with 21 groups of 55 tandem repeat genes. UGT genes were divided into 15 subgroups A-P; group K was lost, and the gene structure and conserved domain of the same subgroup were basically the same. Cis-element analysis showed that upstream 2,000 bp promoter sequence of UGT genes contained light response elements, plant hormone response elements, and stress-related cis-elements, which indicated that UGT genes of Q.robur might be regulated by various metabolic pathways. In particular, some UGTs in group L of Q.robur contained a conserved promoter structure. The expression pattern analysis results demonstrated that UGT genes of groups B, D, E, and I were differentially expressed under Tortrix viridana L stress. The expression of UGTs in group E decreased under stress, the expression of group L increased, and that of genes in groups D and B were different. The functions of UGT genes in E and L groups are relatively conservative, and their functions may also conserved among species. The study results have a particular reference value for further research on the function of Q.robur UGT genes.
Effectiveness of polymyxin B hemoperfusion for sepsis depends on the baseline SOFA score: a nationwide observational study
Authors: Fujimori Kenji , Tarasawa Kunio , Fushimi Kiyohide
Published: May 2021

Background: Polymyxin B hemoperfusion (PMX) aims to prevent septic shock by removing endotoxin from the patient’s blood. However, the relationship between the severity of the patient's organ damage and the efficacy of PMX treatment is not clear.Methods: We analyzed the efficacy of PMX on adult sepsis patients using the propensity score matching method and the Japanese Diagnosis Procedure Combination (DPC) national inpatient database from April 2018 to March 2020. We stratified the patients into five categories based on their baseline sequential organ failure assessment (SOFA) score and compared the mortality between PMX-treated and non-treated groups in each category. We also compared continuous hemodiafiltration (CHDF)-. ventilator- and noradrenaline-free days between the groups.Results: Of 44,177 patients included in the study, 2,191 received PMX. After 1:1 propensity score matching, we created matched cohorts of 2,033 pairs. PMX significantly improved the survival of the patients in the SOFA score categories of 7–9 and 10–12. On the other hand, there was no significant difference in the survival rate in SOFA score categories of 0–6, 13–15, and 16–24. In the analysis of organ support-free days, PMX was also effective in the SOFA categories of 7–9 and 10–12, compared to other categories.Conclusion: Analysis of large-scale Japanese inpatient database found that PMX is effective for patients with moderate severity of organ dysfunction with the SOFA score range of 7 to 12. The study provides essential information for the selection of suitable patients for PMX treatment.
Modelling Wave-Particle Duality of Classical Particles and Waves
Authors: Yang Chen , Oyadiji S. Olutunde
Published: May 2021

Wave-particle duality is the fundamental phenomenon of particles and fields in quantum mechanics. In the past, the trajectory-like (particle-like) behaviour and wave-like behaviour has been considered separately. In this article, a superimposed model is derived to characterise wave-particle duality of classical particles. The superimposed model reflects an invariant mathematical structure (analogous variables and differential equations) from classical mechanics, classical field theories and quantum mechanics. Its analytical solution carries trajectory-like property (phase-independent) and wave-like property (phase-dependent) of particles that is consistent with to Schrodinger’s picture. Subsequently, the presented model is applied to model duality of classical waves in electromagnetism, acoustics and elasticity. The analysis implies the existence of quantum effects of classical waves at macroscopic scale. It predicts quantum picture on energy and momentum exchange between classical particles and waves. As seen in the model, wave-particle duality reflects inherent and indispensable characteristics of classical objects.
Carboxamide Appended Quinoline Moieties as Potential Antiproliferative Agents, Apoptotic Inducers and Pim-1 Kinase Inhibitors
Authors: Ammar Yousry A. , Elhagali Gamil A.M. , Abusaif Moustafa S. , Selim Mohamed R. , Zahran Medhat A. , Naser Tamer , Mehany Ahmed B.M. , Fayed Eman A.
Published: May 2021

The targeted approach of protein kinases (PKs), as PKs are the main regulators of cell survival and proliferation, has been a promising strategy for treatments for cancer. Here we analyze the potential of quinoline-carboximide derivatives for four cell lines: MCF-7, CACO, HepG-2 and HCT-116 as anticancer agents. 3e, 4b, 11b and 13d derivatives showed good anti-proliferative activities in comparison to the reference standard Doxorubicin, against the four cell lines tested. They have been chosen for further studies. First of all, the IC50 value surveys were carried out to ensure the protection of our hits and demonstrate that the cytotoxic effect (IC50 > 113 μM) is highly selective on normal human cells (WI-38). Secondly, apoptosis was accomplished by down-regulation of Bcl-2 and up-regulation of BAX and Caspase-3 by these active compounds. Also, the Pim-1 inhibitory activity of the active hybrids was done, which indicate that compound 3e was the most active with percentage of inhibition 82.27% and IC50 equal 0.11 when compaired to SGI-1776 as a reference standered. In addition, the in silico assessment of ADME properties, all of the strongest compounds are orally bioavailable without blood brain barrier penetration.
Association between Household Exposure and Cycle Threshold in COVID-19 Infected Health Care Workers
Authors: Chien Ai , Domeracki Sandra , Guntur Sandeep , Taylor Kristopher , Lu Chuanyi M. , Lampiris Harry , Blanc Paul D.
Published: May 2021

Objective. Household COVID-19 contact constitutes a high-risk exposure for health care workers (HCWs). Cycle threshold (Ct) of reverse transcriptase–polymerase chain reaction testing provides an estimate of COVID-19 viral load, which can inform clinical and workplace management. We assessed whether Ct values differed between HCWs with and without household exposure. Methods. We analyzed HCW cases whose Ct data could be compared. We defined low Ct at a cut-point approximating a viral load of 4.6x106 copies per ml. Logistic regression tested the association of household exposure and symptoms at diagnosis with a low Ct value. Results. Of 77 HCWs, 20 were household exposures cases and 34 were symptomatic at testing (7 fell were both). Among household exposures, 9 (45%) manifested lower Ct values compared to 14 (25%) of all others. Both household exposure (Odds Ratio [OR] 1.3; 95 % Confidence Interval [CI] 1.03–1.6) and symptoms at diagnosis (OR 1.4; 95% CI 1.15–1.7) were associated a low Ct value. Discussion. Household exposure in HCWs was associated with lower Ct values, consistent with a higher viral load, supporting the hypothesis that contracting COVID-19 in that manner leads to a greater viral inoculum.
Mesenchymal Stem Cells Impact on COVID-19 Patients Immune System, an Ex Vivo Study
Authors: Saraei Raedeh , malekpour kosar , Hazrati Ali , Valizadeh Hamed , Hashemi Behnam , Navashenaq Jamshid Gholizadeh , Roshangar Leila , Yousefi Mehdi , Jadidi-Niaragh Farhad , kafil hossein samadi , Marofi Faroogh , Ahmadi Majid
Published: May 2021

Current clinical management approaches for COVID-19 patients are generally based on supportive treatment, which mainly includes respiratory support and restricted fluid input, which is currently a subject of much debate. Systemic Inflammation caused by SARS-CoV-2 may be related to various extrapulmonary comorbidities such as cytokine-mediated neuroinflammation leading to both non-neuronal and neurological consequences in COVID-19. Mesenchymal stem cells (MSCs) are adult stem cells with multipotent properties suitable for medical applications that have been reported as potential therapies in the setting of lung diseases. The immunosuppressive properties of MSCs provide a strong rationale to explore their potential beneficial effects on immune events in COVID-19. Multiple in vivo studies have demonstrated the capability of MSCs to prevent inflammatory responses and reduce lung damage. Recently, the use of MSCs in treating COVID-19 disease has improved long-term pulmonary function, but the specific mechanisms by which MSCs inhibit the severe inflammatory response induced by SARS-CoV-2 have not been elucidated. To the best of our knowledge, this is the first work describing the regulatory effects of MSCs on peripheral blood mononuclear cells (PBMCs) derived from patients with COVID-19 by measuring the pro-inflammatory and anti-inflammatory cytokines expression and secretion. We also examined the effects on the methylation of genes normally suppressed by DNA methylation in PBMCs. Our result showed that MSCs exerted an immune regulatory function on PBMCs in culture, skewing toward a type-2 response. This occurs by a mechanism consistent with a reduction in inflammatory factors (TNF-α, IL-1β, IL-6, IL-18, and IFNγ) protein and mRNA expression levels. In contrast, the anti-inflammatory cytokines (IL-4 and IL-10) increased following co-culture with MSCs. Consistent with these findings, the DNA methylation status of these immune genes seemed relevant to their expression pattern, except for GATA3, IL-1β, and IFNγ genes which showed no significant differences in methylation level between PBMCs with and without MSC exposure. Moreover, in co-culture interaction, MSCs modulated the Th1/Th2 cells in PBMCs compared to unstimulated PBMCs. These data demonstrate that MSCs can exert important immunomodulatory functions that affect virus-associated cytokine storms in pulmonary tissue during the severe respiratory stage.
Computational quantification of global effects induced by mutations and drugs in signaling networks of colorectal cancer cells
Authors: Sommariva Sara , Caviglia Giacomo , Ravera Silvia , Frassoni Francesco , Benvenuto Federico , Tortolina Lorenzo , Castagnino Nicoletta , Parodi Silvio , Piana Michele
Published: May 2021

Colorectal cancer (CRC) is one of the most deadly and commonly diagnosed tumors worldwide. Several genes are involved in its development and progression. The most frequent mutations concern APC, KRAS, SMAD4, and TP53 genes, suggesting that CRC relies on the concomitant alteration of the related pathways. However, with classic molecular approaches, it is not easy to simultaneously analyze the interconnections between these pathways. To overcome this limitation, recently these pathways have been included in a huge chemical reaction network (CRN) describing how information sensed from the environment by growth factors is processed by healthy colorectal cells. Starting from this CRN, we propose a computational model which simulates the effects induced by single or multiple concurrent mutations on the global signaling network. The model has been tested in three scenarios. First, we have quantified the changes induced on the concentration of the proteins of the network by a mutation in APC, KRAS, SMAD4, or TP53. Second, we have computed the changes in the concentration of p53 induced by up to two concurrent mutations affecting proteins upstreams in the network. Third, we have considered a mutated cell affected by a gain of function of KRAS, and we have simulated the action of Dabrafenib, showing that the proposed model can be used to determine the most effective amount of drug to be delivered to the cell. In general, the proposed approach displays several advantages, in that it allows to quantify the alteration in the concentration of the proteins resulting from a single or multiple given mutations. Moreover, simulations of the global signaling network of CRC may be used to identify new therapeutic targets, or to disclose unexpected interactions between the involved pathways.
Associations of Maternal Complaints to Levator Ani Muscle Trauma Within 9 Months After Vaginal Birth – A Prospective Observational Cohort Study
Authors: Kimmich Nina , Birri Jana , Richter Anne , Zimmermann Roland , Kreft Martina
Published: May 2021

BackgroundPelvic floor trauma in form of partial or complete avulsions of the levator ani muscle (LAM) affects 6-42% of women after vaginal birth and can cause tremendous long-term morbidity. Many studies assessed morphological pelvic floor trauma after childbirth, but lacked to evaluate women`s associated short-term complaints. A proper assessment of trauma and subjective complaints after birth could help to assess possible associations between them and their relevance to women`s daily life. Therefore, we aimed to assess women`s complaints within the first months after birth in association to their LAM trauma.MethodsBetween 3/2017 and 4/2019, we prospectively evaluated vaginal births of 212 primiparous women with singletons in vertex presentation ≥ 36+0 gestational weeks for levator ani muscle (LAM) trauma by translabial ultrasound, for pelvic organ prolapse by clinical examination, and for urogynecological complaints using questionnaires 1-4 days (P1), 6-10 weeks (P2) and 6-9 months (P3) after birth. Women`s complaints were evaluated for P1-P3 according to their LAM trauma state.ResultsAt P1, 67% of women showed an intact LAM, whereas 14.6% presented a hematoma, 6.6% a partial avulsion (PAV) and 11.8% a complete avulsion (CAV). At P2, 75.9% showed an intact LAM, 9.9% a PAV and 14.2% a CAV. At P3, 72.9% of women with a LAM trauma in P1 and/or P2 were assessed, with 21.6% being intact and 39.2% having a PAV and CAV respectively. Obstetrical and baseline characteristics differed slightly between the groups. When comparing the time before and during pregnancy with the time after childbirth, birth itself affected women`s complaints in all LAM state groups, but the presence of a LAM trauma, especially a CAV, had more negative effects. ConclusionsVaginal birth changes the anatomical structure of the maternal birth canal and genital tract, and it alters women`s perceptions and body function. In our study, LAM trauma did not change these effects tremendously within the first months additionally. Therefore, other maternal, fetal and obstetrical factors need consideration for the explanation of maternal complaints, in addition to long-term effects of trauma and dysfunction of the LAM and other birth canal structures.
Understanding Nutrient Imbalances in Maize (Zea mays L.) using the Diagnosis and Recommendation Integrated System (DRIS) Approach in the Maize Belt of Nigeria
Authors: Aliyu Kamaluddin T. , Huising Jeroen , Kamara Alpha Y. , Jibrin Jibrin M. , Mohammed Ibrahim B. , Nziguheba Generose , Adam Adam M. , Vanlauwe Bernard
Published: May 2021

Low nutrient use efficiency in maize as a result of imbalanced nutrition has been reported to drastically reduce yield. We implemented, a nutrient omission experiment to assess the effect of nutrient application on maize yield and nutritional balance. Maize ear leaves were analyzed for nutrients, to identify nutrient balance status using the Diagnostic and Recommendation Integrated System (DRIS) approach. Results indicated that omission of N or P resulted in highly imbalanced DRIS indices respectively, and significantly lower grain yield. A strong inverse relationship between K ear leaf content with DRIS index suggests that K application negatively increases K imbalance in many situations. Imbalances of Mg, Ca and Cu were more associated with higher yielding treatments. A Which-Won-Where result show that nutrient imbalances in the diagnosis were systematically frequent when N was omitted. All the diagnosed nutrients were imbalanced even under the highest yielding NPKZn treatment; indicating further opportunity for yield increase with more balanced nutrition. Balanced nutrition of maize in the maize belt of Nigeria should target application of varying amounts of N, P, K, Mg, S and Zn, depending on the soil condition. But because of complexities of nutrient interactions during uptake, it is hardly possible to realize a balanced nutrition. However, differentiating the application of antagonistic nutrients into foliar or soil-based methods is recommended for a more balanced maize nutrition.
Anomalies of the Aortic Arch in Dogs: Evaluation with the use of Multidetector Computed Tomography and Proposal of an advanced Classification Scheme
Authors: Schorn Christiane , Hildebrandt Nicolai , Schaub Sebastian
Published: May 2021

Background: Congenital anomalies of the aortic arch are important to recognize as they may be associated with vascular rings. The most common vascular ring anomaly in dogs is persistent right aortic arch. However, published data of the distribution and percentage of the different types of vascular rings and other aortic arch anomalies are lacking. The objective of this retrospective descriptive study was to characterize the amount and types of aortic arch anomalies that can be detected in thoracic computed tomography (CT) examination in dogs. Results: Dogs that underwent thoracic CT between 2008 and 2020 were included. A total of 213 CT studies were sampled; 21 dogs (21/213, 9.9%) showed a right aortic arch, and the following additional findings were detected: aberrant left subclavian artery (17/21, 76.2%) branching from the PDA (1/21, 4.8%), left-sided brachiocephalic trunk (3/21, 14.3%), bicarotid trunk (17/21, 81.0%), double aortic arch (1/21, 4.8%). No dog presented right aortic arch without further anomalies. Also, 192 dogs (192/213, 90.1%) showed left aortic arch. The following additional abnormalities were obtained: aberrant right subclavian artery (3/192, 1.6%) without clinical signs of vascular ring, aberrant vessel branching from the aorta into the left caudal lung lobe (2/192, 1.0%), focal dilataion of the left or right subclavian artery (2/192, 1.0%), bicarotid trunk (1/192, 0.5%). Conclusion: The current study indicates that aberrant left subclavian artery is the most common additional finding in dogs with persistent right aortic arch and that left-sided brachiocephalic trunk can occur in dogs, which was previously unpublished. Aberrant right subclavian artery can be an incidental CT finding without clinical relevance.
Predictors of the Worry About Cancer Recurrence Among Women With Breast Cancer
Authors: Safdari-Molan Masoumeh , Mehrabi Esmat , Nourizadeh Roghaiyeh , Hakimi Sevil , Nikkhesal Neda
Published: May 2021

Introduction: Worry about cancer recurrence is identified as the most common psychological burdens experienced by cancer patients and survivors. The present study aimed to determine the predictors of worry about cancer recurrence among women with breast cancer. Materials and methods: This cross-sectional study was conducted on 166 women with breast cancer undergoing chemotherapy and radiotherapy, who referred to private and public oncology centers in Tabriz, Iran using the convenience sampling method. Data collection tools were demographic and disease characteristics questionnaire, cancer worry scale, social support questionnaire, brief illness perception questionnaire, international physical activity questionnaire-short form, and The EORTC-in-patsat32. The data were analyzed using SPSS 25 software. Pearson correlation coefficient, independent t-test, ANOVA, and multivariate linear regression were used.Results: In the present study, the mean (standard deviation) of score of worry about cancer recurrence was 17.41 (7.88) from the range of 8-32. The results revealed that the type of surgery, illness perception, satisfaction with care, and place of treatment were the most important predictors of worry about cancer recurrence, which explained 44.3% of the variance.Conclusion: The enhancement of satisfaction with care and training coping strategies among individuals with high perceived severity of the illness contribute to the reduction of worry about cancer recurrence and adaptation to breast cancer.
Audio-visual Stimulation for Visual Compensatory Functions in Stroke Survivors With Visual Field Defect; a Systematic Review
Authors: Alwashmi Kholoud , Meyer Georg , Rowe Fiona J
Published: May 2021

Background: Hemianopia is a complete or partial blindness in the visual fields of both eyes, commonly caused by cerebral infarction. It has been hypothesized that systematic audio-visual (AV) stimulation of the blind hemifield can improve accuracy and search times in visual exploration, probably due to the stimulation of bimodal representations in the Superior Colliculus (SC), an important multisensory structure involved in both the initiation and execution of saccades. The review aimed to assess evidence for the effectiveness of AV stimulation as a rehabilitation strategy for stroke survivors with hemianopia in adult- and childhood.Methods: This review is registered with PROSPERO. A narrative synthesis of the findings is presented to highlight how AV rehabilitation impacts on hemianopia patients including visual oculomotor function, functional ability in activities of daily living, hemianopic dyslexia, visual scanning and searching tasks, maintaining of functional ability post training and the effect on brain multisensory integration by using neuroimaging.Results: Sixteen studies were included; fourteen articles (188 participants) and two literature reviews. Results were grouped into AV training of hemianopia in adults and in children, and then further grouped according to the AV task-type: tasks measuring the training effects by comparing visual stimulation training to audio-visual training, localization abilities in HH, and AV integration in patients with HH.Conclusion: The review findings support the concept that compensatory audio-visual training can be useful as rehabilitation method for stroke survivors with hemianopia. Systematic AV training may improve the processing of visual information by recruiting subcortical pathways, and because most of the patients with visual cortex damage have an intact SC, it might be useful to use the bimodal AV training to activate retinotectal functions. Nevertheless, the underlying mechanisms supporting the reported positive effects are not currently understood. Systematic functional and/or structural imaging studies may help in understanding the underlying mechanism and inform the design of optimal training paradigms.Systematic review registration: This review is registered with PROSPERO by the correspondence author (CRD42020197348).
Standardized Assessment of Simulation Based ECMO Educational Courses: A Pilot Study
Authors: Said Ahmed S , Cooley Elaine , Diaz Rodrigo , Moore Elizabeth A , Shekar Kiran , Beaty Christopher , Maul Timothy M , Kollengode Ramanathan , Zakhary Bishoy
Published: May 2021

Background: The Extracorporeal Life Support Organization (ELSO) education taskforce (ELSOed) recently identified seven extracorporeal membrane oxygenation (ECMO) educational domains that would benefit from international collaborative efforts among which standardized assessments of ECMO courses was prioritized. We aimed to develop a standardized online assessment tool to evaluate the effectiveness of a comprehensive didactic and simulation-based ECMO course on participants’ gain in confidence, knowledge, and simulation-based skills.Methods: We performed a prospective multicenter observational study of five US adult ECMO courses. Standardized online assessment forms were developed and administered before and after courses, covering demographics, self-assessment regarding ECMO management, and knowledge exam (15 simple-recall multiple choice questions), while psychomotor skill assessment was performed during the course (time to complete pre-specified critical actions during simulation scenarios). Self-assessment covered cognitive, behavioral, and technical aspects of ECMO care.Results: Out of 211 participants, 107 completed both pre- and post-course forms (97 completed both pre and post-course knowledge forms). Physician-intensivists were the largest group (53%) and the majority practiced at academic hospitals (51%) and had less than 1-year of ECMO experience (50%). Post-course, participants reported significant increases in confidence across all domains (cognitive, technical, and behavioral; p<0.0001 CI:1.2-1.5, p<0.0001 CI:2.2-2.6, and p=0.002 CI:1.7-2.1, respectively) as well as an increase in knowledge scores (p<0.001, CI: 1.4-2.5). These findings were consistent for all specialties and prior ECMO experience. There were also significant reductions in the times to critical actions in 3 of the 4 scored simulation scenarios.Conclusions: We successfully developed and tested a comprehensive standardized ECMO course assessment tool, demonstrating participants’ self-reported benefit as well as improvement in both knowledge and psychomotor skill acquisition . Standardized course evaluation is feasible and potentially provides important information to improve ECMO courses. Future steps include national implementation, addition of questions targeting clinical decision making to further assess knowledge gain, and multi-language translation for implementation at international courses.
Non-invasive Estimation of Pulsatile and Static Intracranial Pressure by Optical Coherence Tomography
Authors: Jacobsen Henrik Holvin , Jørstad Øystein Kalsnes , Moe Morten C. , Petrovski Goran , Pripp Are Hugo , Sandell Tiril , Eide Per Kristian
Published: May 2021

This study examined whether optical coherence tomography (OCT) can be used to estimate the pulsatile and static intracranial pressure (ICP) in patients with idiopathic intracranial hypertension (IIH). Continuous overnight monitoring of the pulsatile and static ICP and a single OCT examination were performed in 20 patients with IIH and in 12 reference subjects without cerebrospinal fluid disturbances. The ICP measurements were obtained using a parenchymal sensor. The pulsatile ICP was determined as the mean ICP wave amplitude (MWA) and the static ICP was determined as the mean ICP. The IIH group had increased overnight MWA and mean ICP scores, and OCT demonstrated anterior deflection of the peripapillary Bruch’s membrane angle (pBA) and increased optic nerve head height (ONHH). There was a significant positive correlation between the pBA and ONHH and the overnight MWA scores, and between mean ICP and ONHH. The pBA and the ONHH also predicted abnormal overnight MWA, but the predictive power of mean ICP was non-significant after adjusting for age and body mass index. This study suggest that the OCT parameters pBA and ONHH can predict abnormal MWA scores.
Vanishing pachy-choroid in pachychoroid neovasculopathy under long-term anti-vascular endothelial growth factor therapy
Authors: Schworm Benedikt , Luft Nikolaus , Keidel Leonie F , Kreutzer Thomas C , Herold Tina R , Priglinger Siegfried G , Siedlecki Jakob
Published: May 2021

BackgroundTo investigate the diagnostic value of choroidal thickness in the definition of pachychoroid neovasculopathy (PNV), especially in eyes treated with anti-vascular endothelial growth factor (VEGF) therapy.MethodsTwenty-two consecutive eyes of 11 patients with uni- or bilateral PNV were analyzed. Anti-VEGF treatment was correlated with changes in choroidal thickness on enhanced depth imaging optical coherence tomography.ResultsThere were 14 eyes with PNV and 8 non-neovascular partner eyes. Mean age was 64.2 ± 4.0 (range: 60–72), total follow-up was 1.8 ± 0.4 (1–2) years. In PNV eyes, choroidal thickness at baseline was 400 ± 58 (269–485) µm. After two years and 13 anti-VEGF injections on average, a mean reduction of -39 ± 10 (-26 to -56) % to final 241 ± 52 (162–327) µm was observed (p < 0.0001). Meanwhile, choroidal thickness in the partner eyes remained stable (p > 0.13 for all comparisons). A significant correlation of choroidal thinning and anti-VEGF injection rate was observed at year one (r=-0.79 ; R2 = 0.63 ; p = 0.00073) and two (r=-0.69; R2 = 0.48 ; p = 0.019). While 85.7 % of PNV eyes exceeded a pachychoroid threshold of ≥ 350 µm at baseline, this figure dropped to 21.4 % at year one and 0 % at year two.ConclusionIn PNV, choroidal thickness significantly decreases with anti-VEGF therapy, resembling a “vanishing pachy-choroid”, and thus does not represent a valid long-term diagnostic criterium, especially when differentiating PNV from nAMD.
De Novo Biosynthesis of Glycosylated Carotenoids in Escherichia Coli
Authors: Chen Xixian , Lim Xiaohui , Bouin Aurelie , Lautier Thomas , Zhang Congqiang
Published: May 2021

Carotenoids have wide applications in food, feed, pharmaceutical and cosmetic industries. The fast-growing market demands highlight the importance of developing new routes for carotenoid biosynthesis. Meanwhile, a complementary need is to improve low bioavailability because of the hydrophobicity of carotenoids. One solution is glycosylation, which can substantially increase the water solubility of carotenoids, and enhance the bioavailability, photostability and biological activities as food supplements and medicines. Here, we report metabolic engineering efforts to produce glycosylated carotenoids in Escherichia coli . By fine tuning the 14 gene pathway, our strain produced up to 47.2 mg/L (~11670 ppm) of zeaxanthin glucosides, ~78% of the total carotenoids produced. In another construct with 15-gene pathway, the strain produced a mixture of carotenoid glucosides including astaxanthin and adonixanthin glucosides with a total yield of 8.1 mg/L (1774 ppm). Our work demonstrated a proof-of-concept study for the microbial biosynthesis of glycosylated carotenoids. (145 words)
Economic Evaluation of Community-based Falls Prevention Interventions: a Systematic Methodological Overview of Systematic Reviews
Authors: Kwon Joseph , Lee Yujin , Squires Hazel , Franklin Matt , Young Tracey
Published: May 2021

Background: Falls impose significant health and economic burdens on older people, making their prevention a priority for care decision-makers. The volume of falls prevention economic evaluations has increased, the findings from which have been synthesised by systematic reviews (SRs) with pre-specified criteria (e.g., objectives, eligibility, data extraction). Such SRs can inform commissioning and design of future evaluations, particularly decision models; however, their findings can be biased and partial dependent on their pre-specified criteria. This study aims to conduct a systematic overview (SO) to: (1) systematically identify SRs of community-based falls prevention economic evaluations; (2) describe the methodology and findings of SRs; (3) critically appraise the methodology of SRs; and (4) suggest commissioning recommendations based on SO findings. Methods: The SO followed the PRISMA guideline and the Cochrane guideline on SO, covering the period 2003-2020. Identified SRs’ aims, search strategies and results, extracted data fields, quality assessment methods and results, and commissioning and research recommendations were synthesised. The comprehensiveness of previous SRs’ data synthesis was judged against criteria drawn from expert guideline and academic literature on falls prevention/public health economic evaluation. Outcomes of general population, lifetime decision models were re-analysed to inform commissioning recommendations. The SO protocol is registered in the Prospective Register of Systematic Reviews (CRD42021234379).Results: Seven SRs were identified, which extracted 8 to 33 data fields from 44 relevant economic evaluations. Four economic evaluation methodological/reporting quality checklists were used; three SRs narratively synthesised methodological features to varying extent and focus. SRs generally did not appraise decision modelling features, including methods for characterising dynamic complexity of falls risk and intervention need. Their commissioning recommendations were based mainly on cost-per-unit ratios (e.g., incremental cost-effectiveness ratios) and neglected aggregate impact. There is model-based evidence of multifactorial and environmental interventions, home assessment and modification and Tai Chi being cost-effective but also the risk that they exacerbate social inequities of health. Conclusions: Current SRs of falls prevention economic evaluations do not holistically inform commissioning and evaluation design. Accounting for broader decisional factors including intervention reach and capacity constraints and a broader grasp of methodological nuances of economic evaluations, particularly decision models, are needed.
Phosphorylation of CAP1 Regulates Lung Cancer Proliferation, Migration and Invasion
Authors: Zeng Jie , Li Xuan , Liang Long , Duan Hongxia , Xie Shuanshuan , Wang Changhui
Published: May 2021

Purpose: Cyclase-associated protein 1 (CAP1) is a ubiquitous protein which regulates actin dynamics. Comprehensive bioinformatics analysis showed CAP1 is a type of cancer-related protein. Previous studies have shown that the protein CAP1 can be phosphorylated. S308 and S310 are the two major phosphorylated sites in human CAP1. In the present study, we aimed to investigate the mechanism of lung cancer metastasis mediated by CAP1. Methods: Massive bioinformatics analysis were applied to determine CAP1’s role in different cancers and especially in lung cancer. Lung cancer patients’ serum was collected and analyzed. CAP1 shRNA-lentivirus were applied to CAP1 gene knockdown, and plasmids were constructed for CAP1 phosphorylation and dephosphorylation. Microarray analysis was used for CAP1-associated difference analysis. Both in vitro and in vivo experiments were performed to investigate the roles of CAP1 phosphorylation and dephosphorylation in lung cancer A549 cells. Results: CAP1 is a kind of cancer related protein. Its mRNA was overexpressed in most types of cancer tissues when compared with normal tissues. CAP1 high expression correlated with poor prognosis. Our results showed that serum CAP1 protein concentrations were significantly upregulated in non-small cell lung cancer (NSCLC) patients when compared with the healthy control group. Knockdown CAP1 in A549 cells can inhibit proliferation and migration. It can also lead to an increase ratio of F-actin/G-actin. In addition, phosphorylated S308 and S310 in CAP1 promoted lung cancer cell proliferation, migration and metastasis both in vitro and in vivo. When dephosphorylated these two sites in CAP1 showed the opposite effect. Phosphorylation of CAP1 can promote epithelial–mesenchymal transition (EMT). Conclusion: These findings indicated that phosphorylation sites of CAP1 might be a novel target for lung cancer treatment.
Establishment of a Gunshot Model of Junctional Femoral Artery Hemorrhage in Swine Under Ultrasonic Guidance
Authors: Zhang Hongliang , Guo Chengyu , Wang Junkang , Feng Cong , Li Tanshi
Published: May 2021

Background: In a combat setting, uncontrolled junctional hemorrhage, which occur at the junction of the torso and appendages, constitutes a major source of potentially preventable deaths. A reliable gunshot swine model of junctional femoral artery rupture was established under ultrasonic guidance to accurately simulate field rescue conditions. Methods: Picco monitoring was instrumented for the anesthetized Landrace pigs, and the right femoral artery was located by portable ultrasound. The pistol bullet hit the right femoral artery along the direction of ultrasonic probe, resulting in the artery rupture. After 30 seconds of uncontrolled hemorrhage, ballistic was filled with Combat Gauze to stop bleeding in BT group (n=10). Combat Gauze (QuikClot) was used to stop bleeding when the mean arterial pressure (MAP) decreased by 30% in MD group (n=10). The sham-operated pigs (n=10) underwent the same anesthetic and surgical procedures, but neither shooting nor gauze filling therapy were performed. No liquid treatment was performed in the three groups throughout the experiment. Blood samples were taken 15 min before injury, then 10 min, 30 min, and 60 min after injury to determine hemodynamic, coagulation, and arterial blood gas indexes. Animals were then monitored for 180 minutes and surviving animals were killed. Results: Histologic anatomy indicated that the right femoral artery and vein were completely ruptured in all 20 swine of MD and BT groups. Eighteen pigs had associated proximal femur fractures and the other two had associated midshaft femur fractures. The entrance diameters of wound were 11.4 mm (SD=0.4), and the exits diameters were 26.4 mm (SD=5.8). The blood loss of pre-tamponade (4.97±2.47 mL/kg vs 18.26±3.47 mL/kg, P<0.001), pro-tamponade (4.58±1.49 mL/kg vs 7.20±1.99 mL/kg, P=0.004) and the total amount of bleeding (9.54±3.80 mL/kg vs 25.46±3.68 mL/kg, P<0.001) in MD group were more than those in BT group. There was statistic difference in the PT, PH, LAC of three groups (P=0.005, 0.004, and<0.001, respectively) and in the body temperature, PH, LAC of different time points (all P<0.001). There were differences in body temperature, PH, PT, LAC of MD group compared with BT and SHAM groups 60 minutes after injury (all P<0.0167). The survival time of MD group was shorter than that of BT group (P=0.029). Conclusion: We established a reliable gunshot model of junctional hemorrhage in swine, which had high accuracy for femoral arterial rupture under ultrasonic guidance and provided consistent and reproducible field-simulation conditions. In this junctional hemorrhage model, blood loss of 30 seconds free bleeding did not meet criteria for shock, and MAP decreased by 30% is a better choice to ensure the success of the shock model.Trial registration: Authorized by Institutional Animal Care and Use Committee in China (grant no. SC2019-06-013).
Optimal mean arterial pressure for favorable neurological outcomes in survivors after extracorporeal cardiopulmonary resuscitation
Authors: Lee Yun Im , Ko Ryoung-Eun , Yang Jeong Hoon , Cho Yang Hyun , Ahn Joonghyun , Ryu Jeong-Am
Published: May 2021

Background: This study aimed to evaluate the optimal target of mean arterial pressure (MAP) for favorable neurological outcomes in patients who underwent extracorporeal cardiopulmonary resuscitation (ECPR).Methods: This was a retrospective, single-center, and observational study of adult patients who underwent ECPR during hospitalization between January 2013 and December 2019. The average MAP was defined as the sum of obtained MAPs divided by their obtained numbers of times during 6, 12, 24, 48, 72, and 96 hrs after cardiac arrest, respectively. The primary outcome was the neurological status upon discharge, as assessed by the Cerebral Performance Categories (CPC) scale (range from 1 to 5). Results: Ultimately, 253 patients were analyzed in this study. Among these patients, 144 (56.9%) survived until discharge from the hospital. Of these survivors, 104 patients had favorable neurologic outcomes (CPC 1 or 2). Overall, patients with favorable neurological outcomes tended to have a higher average MAP than those with poor neurological outcomes. Ensemble algorithms for machine learning and multiple logistic regression revealed that age, Glasgow Coma Scale (GCS) on admission, duration of cardiopulmonary resuscitation (CPR) and average MAPs were significantly associated with neurological outcomes. Six models were established based on these variables and observation times. There was no significant difference in the predicted performance between the 6 hrs model and other models. The patients with average MAP around 75 mmHg had the least probability of poor neurologic outcomes in all the models. However, those with average MAPs below 60 mmHg had a high probability of poor neurological outcomes. Also, based on an increase in the average MAP, the risk of poor neurological outcomes tended to increase in patients with an average MAP greater than 75 mmHg.Conclusions: In this study, age, GCS on admission, CPR duration and average MAPs were identified to be associated with neurological outcomes. Especially, it is hypothesized that the average MAP during the initial 6 hrs may be associated with secondary cerebral injury. Therefore, it is theorized that at an early stage, maintaining the survivor’s MAP to about 75 mmHg may be important for neurological recovery after ECPR.