bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward an Anti-Racist Curriculum: Incorporating Art into Medical Education to Improve Empathy and Structural Competency
Authors: Godley Bria Adimora , Dayal Diana , Manekin Elizabeth , Estroff Sue E
Published: October 2020

Background:

There is an urgent need for medical school curricula that address the effects of structural influences, particularly racism, on health, healthcare access, and the quality of care for people of color. Underrepresented racial minorities in the United States receive worse health care relative to their White counterparts. Structural competency, a framework for recognizing and understanding social influences on health, provides a means for understanding the structural violence that results from and perpetuates racism in classroom and clinical education. Some medical schools have incorporated art into their curricula to increase empathy generally, yet few programs use art to address racial disparities in medicine specifically.

Objective:

“Can We Talk About Race?” (CWTAR) aims to increase medical students’ empathy for racial minorities and increase the ease and ability of students to address racial issues. CWTAR also provides a unique context for ongoing conversations about racism and structural inequality within the health care system.

Methods:

Sixty-four first-year medical students were randomly selected to participate in CWTAR. The on-campus Ackland Art Museum staff and trained student facilitators lead small group discussions on selected artworks. A course evaluation was sent to all participants consisting of 4 questions: (1) Likert scale rating the quality of the program, (2) the most important thing learned from the program, (3) any differences between discussion at this program versus other conversations around race, and (4) suggestions for changes to the program. Free text responses were content coded and analyzed to reveal common themes.

Results:

Out of 64 students, 63 (98%) responded to at least one course evaluation question. The majority (89%) of participants rated the program quality as either “Very Good” or “Excellent.” Of the 37 students who responded to the free text question regarding the most important thing they learned from the program, 16 (44%) responses revealed students felt that they were exposed to perspectives that differed from their own, and 19% of respondents reported actively viewing a subject through another’s perspective. Of the 33 students who responded to the free text question regarding any differences between discussion at this program versus other conversations around race, 48% noted an increased comfort level discussing race during the program. A common theme in responses to the question regarding suggested changes to the program was a more explicit connection to medicine in the discussion around race.

Conclusions:

Student responses to CWTAR suggest that the program is effective in engaging students in discussions of racial issues. More investigation is needed to determine whether this methodology increases empathy among medical students for racial minorities specifically.
Multiple evanescent white dot syndrome and panuveitis: a case report
Authors: Mizuuchi Kazuomi , Saito Wataru , Namba Kenichi , Ishida Susumu
Published: October 2020

Aim

To report a patient with multiple evanescent white dot syndrome (MEWDS) complicated by iridocyclitis and vitritis.

Case description

A 70-year-old woman developed multiple subretinal white dots, iritis, and diffuse vitreous opacity. Angiographic and macular morphological features were consistent with those of MEWDS. Inflammatory findings including the white dots improved following only topical dexamethasone within 1 month after the initial visit. Best-corrected visual acuity recovered to 1.0 with restored photoreceptor structure.

Conclusion

The presence of iridocyclitis and vitritis, atypical to MEWDS, indicates the concurrent development of panuveitis associated with MEWDS. These results suggest that MEWDS is a clinical entity of uveitis.
Do ethnicity and sex of employers affect applicants’ job interest? An experimental exploration
Authors: Granberg Mark , Ottosson Niklas , Ahmed Ali
Published: October 2020

Starting a business is one way out of unemployment for many people. Having a small pool of job applicants may, however, affect the quality of manpower available to employers. This paper reports the results of an experimental study that examined whether job-seekers discriminate against prospective employers based on those employers’ ethnicity and sex. We conducted an experiment with 889 university students, where we presented 10 hypothetical job vacancies in the restaurant sector to the participants. We then asked participants to state their willingness to apply to each job. The ethnicity and sex of the employers were conveyed through employers’ names by using typical male and female Arabic- and Swedish-sounding names. Overall, our results provided no evidence of ethnic or sex discrimination by job-seekers against employers.
Feature selection algorithm based on dual correlation filters for cancer-associated somatic variants
Authors: Seo Hyein , Cho Dong-Ho
Published: October 2020

Background

Since the development of sequencing technology, an enormous amount of genetic information has been generated, and human cancer analysis using this information is drawing attention. As the effects of variants on human cancer become known, it is important to find cancer-associated variants among countless variants.

Results

We propose a new filter-based feature selection method applicable for extracting cancer-associated somatic variants considering correlations of data. Both variants associated with the activation and deactivation of cancer’s characteristics are analyzed using dual correlation filters. The multiobjective optimization is utilized to consider two types of variants simultaneously without redundancy. To overcome high computational complexity problem, we calculate the correlation-based weight to select significant variants instead of directly searching for the optimal subset of variants. The proposed algorithm is applied to the identification of melanoma metastasis or breast cancer stage, and the classification results of the proposed method are compared with those of conventional single correlation filter-based method.

Conclusions

We verified that the proposed dual correlation filter-based method can extract cancer-associated variants related to the characteristics of human cancer.
LAMP: disease classification derived from layered assessment on modules and pathways in the human gene network
Authors: Mi Zhilong , Guo Binghui , Yang Xiaobo , Yin Ziqiao , Zheng Zhiming
Published: October 2020

Background

Classification of diseases based on genetic information is of great significance as the basis for precision medicine, increasing the understanding of disease etiology and revolutionizing personalized medicine. Much effort has been directed at understanding disease associations by constructing disease networks, and classifying patient samples according to gene expression data. Integrating human gene networks overcomes limited coverage of genes. Incorporating pathway information into disease classification procedure addresses the challenge of cellular heterogeneity across patients.

Results

In this work, we propose a disease classification model LAMP, which concentrates on the layered assessment on modules and pathways. Directed human gene interactions are the foundation of constructing the human gene network, where the significant roles of disease and pathway genes are recognized. The fast unfolding algorithm identifies 11 modules in the largest connected component. Then layered networks are introduced to distinguish positions of genes in propagating information from sources to targets. After gene screening, hierarchical clustering and refined process, 1726 diseases from KEGG are classified into 18 categories. Also, it is expounded that diseases with overlapping genes may not belong to the same category in LAMP. Within each category, entropy is applied to measure the compositional complexity, and to evaluate the prospects for combination diagnosis and gene-targeted therapy for diseases.

Conclusion

In this work, by collecting data from BioGRID and KEGG, we develop a disease classification model LAMP, to support people to view diseases from the perspective of commonalities in etiology and pathology. Comprehensive research on existing diseases can help meet the challenges of unknown diseases. The results provide suggestions for combination diagnosis and gene-targeted therapy, which motivates clinicians and researchers to reposition the understanding of diseases and explore diagnosis and therapy strategies.
Effects of propofol on intracranial pressure and prognosis in patients with severe brain diseases undergoing endotracheal suctioning
Authors: Wu Menghang , Yin Xiaorong , Chen Maojun , Liu Yan , Zhang Xia , Li Tingting , Long Yujuan , Wu Xiaomei , Pu Lihui , Zhang Maojie , Hu Zhi , Ye Ling
Published: October 2020

Background

To investigate whether the administration of intravenous propofol before endotracheal suctioning (ES) in patients with severe brain disease can reduce the sputum suction response, improve prognosis, and accelerate recovery.

Methods

A total of 208 severe brain disease patients after craniocerebral surgery were enrolled in the study. The subjects were randomly assigned to the experimental group (n = 104) and the control group (n = 104). The experimental group was given intravenous propofol (10 ml propofol with 1 ml 2% lidocaine), 0.5–1 mg/kg, before ES, while the control group was subjected to ES only. Changes in vital signs, sputum suction effect, the fluctuation range of intracranial pressure (ICP) before and after ES, choking cough response, short-term complications, length of stay, and hospitalization cost were evaluated. Additionally, the Glasgow Outcome Scale (GOS) prognosis score was obtained at 6 months after the operation.

Results

At the baseline, the characteristics of the two groups were comparable (P > 0.05). The increase of systolic blood pressure after ES was higher in the control group than in the experimental group (P < 0.05). The average peak value of ICP in the experimental group during the suctioning (15.57 ± 12.31 mmHg) was lower than in the control group (18.24 ± 8.99 mmHg; P < 0.05). The percentage of patients experiencing cough reaction- during suctioning in the experimental group was lower than in the control group (P < 0.05), and the fluctuation range of ICP was increased (P < 0.0001). The effect of ES was achieved in both groups. The incidence of short-term complications in the two groups was comparable (P > 0.05). At 6 months after the surgery, the GOS scores were significantly higher in the experimental than in the control group (4–5 points, 51.54% vs. 32.64%; 1–3 points, 48.46% vs. 67.36%; P < 0.05). There was no significant difference in the length of stay and hospitalization cost between the two groups.

Conclusions

Propofol sedation before ES could reduce choking cough response and intracranial hypertension response. The use of propofol was safe and improved the long-term prognosis.

The study was registered in the Chinese Clinical Trial Registry on May 16, 2015 (ChiCTR-IOR-15006441).
Minimally invasive versus open right hepatectomy: comparative study with propensity score matching analysis
Authors: Duarte Vinícius Campos , Coelho Fabricio Ferreira , Valverde Alain , Danoussou Divia , Kruger Jaime Arthur Pirola , Zuber Kevin , Fonseca Gilton Marques , Jeismann Vagner Birk , Herman Paulo , Lupinacci Renato Micelli
Published: October 2020

Background

Minimally invasive liver resections (MILRs) have been increasingly performed in recent years. However, the majority of MILRs are actually minor or limited resections of peripheral lesions. Due to the technical complexity major hepatectomies remain challenging for minimally invasive surgery. The aim of this study was to compare the short and long-term outcomes of patients undergoing minimally invasive right hepatectomies (MIRHs) with contemporary patients undergoing open right hepatectomies (ORHs)

Methods

Consecutive patients submitted to anatomic right hepatectomies between January 2013 and December 2018 in two tertiary referral centers were studied. Study groups were compared on an intention-to-treat basis after propensity score matching (PSM). Overall survival (OS) analyses were performed for the entire cohort and specific etiologies subgroups

Results

During study period 178 right hepatectomies were performed. After matching, 37 patients were included in MIRH group and 60 in ORH group. The groups were homogenous for all baseline characteristics. MIRHs had significant lower blood loss (400 ml vs. 500 ml, P = 0.01), lower rate of minor complications (13.5% vs. 35%, P = 0.03) and larger resection margins (10 mm vs. 5 mm, P = 0.03) when compared to ORHs. Additionally, a non-significant decrease in hospital stay (ORH 9 days vs. MIRH 7 days, P = 0.09) was observed. No differences regarding the use of Pringle’s maneuver, operative time, overall morbidity or perioperative mortality were observed. OS was similar between the groups (P = 0.13). Similarly, no difference in OS was found in subgroups of patients with primary liver tumors (P = 0.09) and liver metastasis (P = 0.80).

Conclusions

MIRHs are feasible and safe in experienced hands. Minimally invasive approach was associated with less blood loss, a significant reduction in minor perioperative complications, and did not negatively affect long-term outcomes.
Behind bars: the burden of being a woman in Brazilian prisons
Authors: de Araújo Priscila França , Kerr Ligia Regina Franco Sansigolo , Kendall Carl , Rutherford George W. , Seal David W. , da Justa Pires Neto Roberto , da Costa Pinheiro Patrícia Neyva , Galvão Marli Teresinha Gimeniz , Araújo Larissa Fortunato , Pinheiro Francisco Marto Leal , da Silva Ana Zaira
Published: October 2020

Background

Brazil has the third largest prison population in the world. In 2016, the female prison population totaled 42,000, an increase of 656% over the population recorded in the early 2000s. The objective of this study was to describe the socialeconomic and reproductive health of women in Brazilian prisons, and the specific assistance received within the prison system.

Methods

This is a first of its kind national survey conducted in 15 female prisons in eight Brazilian states between 2014 and 2015. The sample consisted of 1327 women in closed or semi-open prison regimes. Data collection used Audio Computer-Assisted Self-Interviewing (ACASI). STATA v.15. Was use in analysis. The study was submitted to the Research Ethics Committee of the Federal University of Ceará, under CEP protocol No. 1,024,053.

Results

The population was overwhelmingly Black or Brown, poor and little educated. When women worked previously, they had worked as domestic servants and were the sole source of income for their families. Most were mothers, with 39% having children less than 10 years old, now in the care of others. Most were in jail for drug-related crimes. Prisons were crowded, with more than 2/3rds of the inmates sharing a cell with 6 or more inmates. Services were provide, but women had not had a cervical cancer screening within the past 3 years and breast cancer screening was not conducted.

Conclusions

Overall, given their backround and prison conditions they are unlikely to change the circumstances that brought them to prison in the first place.
Transformational improvement in quality care and health systems: the next decade
Authors: Braithwaite Jeffrey , Vincent Charles , Garcia-Elorrio Ezequiel , Imanaka Yuichi , Nicklin Wendy , Sodzi-Tettey Sodzi , Bates David W.
Published: October 2020

Background

Healthcare is amongst the most complex of human systems. Coordinating activities and integrating newer with older ways of treating patients while delivering high-quality, safe care, is challenging. Three landmark reports in 2018 led by (1) the Lancet Global Health Commission, (2) a coalition of the World Health Organization, the Organisation for Economic Co-operation and Development and the World Bank, and (3) the National Academies of Sciences, Engineering and Medicine of the United States propose that health systems need to tackle care quality, create less harm and provide universal health coverage in all nations, but especially low- and middle-income countries. The objective of this study is to review these reports with the aim of advancing the discussion beyond a conceptual diagnosis of quality gaps into identification of practical opportunities for transforming health systems by 2030.

Main body

We analysed the reports via text-mining techniques and content analyses to derive their key themes and concepts. Initiatives to make progress include better measurement, using the capacities of information and communications technologies, taking a systems view of change, supporting systems to be constantly improving, creating learning health systems and undergirding progress with effective research and evaluation. Our analysis suggests that the world needs to move from 2018, the year of reports, to the 2020s, the decade of action. We propose three initiatives to support this move: first, developing a blueprint for change, modifiable to each country’s circumstances, to give effect to the reports’ recommendations; second, to make tangible steps to reduce inequities within and across health systems, including redistributing resources to areas of greatest need; and third, learning from what goes right to complement current efforts focused on reducing things going wrong. We provide examples of targeted funding which would have major benefits, reduce inequalities, promote universality and be better at learning from successes as well as failures.

Conclusion

The reports contain many recommendations, but lack an integrated, implementable, 10-year action plan for the next decade to give effect to their aims to improve care to the most vulnerable, save lives by providing high-quality healthcare and shift to measuring and ensuring better systems- and patient-level outcomes. This article signals what needs to be done to achieve these aims.
Granulocyte-colony stimulating factor gene therapy as a novel therapeutics for stroke in a mouse model
Authors: Menzie-Suderam Janet M. , Modi Jigar , Xu Hongyaun , Bent Andrew , Trujillo Paula , Medley Kristen , Jimenez Eugenia , Shen Jessica , Marshall Michael , Tao Rui , Prentice Howard , Wu Jang-Yen
Published: October 2020

Background

Global ischemia is the resulting effect of a cardiopulmonary arrest (CPA). Presently there is no effective treatment to address neurological deficits in patients who survived a CPA. Granulocyte-colony stimulating factor is a growth factor (G-CSF) with a plethora of beneficial effects, including neuroprotection. Clinical application of human G-CSF (hG-CSF) is limited due to its plasma half-life of 4 h. Therefore, novel approaches need to be investigated that would (1) enable prolonged manifestation of hG-CSF and (2) demonstrate G-CSF efficacy from studying the underlying protective mechanisms of hG-CSF. In our previous work, we used the self-complementary adeno-associated virus (stereotype2: scAAV2) as a vector to transfect the hG-CSF gene into the global ischemic brain of a mouse. As an extension of that work, we now seek to elucidate the protective mechanisms of hG-CSF gene therapy against endoplasmic reticulum induced stress, mitochondrial dynamics and autophagy in global ischemia.

Method

A single drop of either AAV-CMV-hG-CSF or AAV-CMV-GFP was dropped into the conjunctival sac of the Swiss Webster mouse’s left eye, 30–60 min after bilateral common artery occlusion (BCAO). The efficacy of the expressed hG-CSF gene product was analyzed by monitoring the expression levels of endoplasmic reticulum stress (ER), mitochondrial dynamics and autophagic proteins over 4- and 7-days post-BCAO in vulnerable brain regions including the striatum, overlying cortex (frontal brain regions) and the hippocampus (middle brain regions). Statistical analysis was performed using mostly One-Way Analysis of variance (ANOVA), except for behavioral analysis, which used Repeated Measures Two-Way ANOVA, post hoc analysis was performed using the Tukey test.

Results

Several biomarkers that facilitated cellular death, including CHOP and GRP78 (ER stress) DRP1 (mitochondrial dynamics) and Beclin 1, p62 and LC3-ll (autophagy) were significantly downregulated by hG-CSF gene transfer. hG-CSF gene therapy also significantly upregulated antiapoptotic Bcl2 while downregulating pro-apoptotic Bax. The beneficial effects of hG-CSF gene therapy resulted in an overall improvement in functional behavior.

Conclusion

Taken together, this study has substantiated the approach of sustaining the protein expression of hG-CSF by eye drop administration of the hG-CSF gene. In addition, the study has validated the efficacy of using hG-CSF gene therapy against endoplasmic reticulum induced stress, mitochondrial dynamics and autophagy in global ischemia.
Differential role of segments of α-mating factor secretion signal in Pichia pastoris towards granulocyte colony-stimulating factor emerging from a wild type or codon optimized copy of the gene
Authors: Aggarwal Sakshi , Mishra Saroj
Published: October 2020

Background

The methylotrophic yeast, Pichia pastoris has been widely used for the production of human therapeutics, but production of granulocyte colony-stimulating factor (G-CSF) in this yeast is low.The work reported here aimed to improve the extracellular production of G-CSF by introducing mutations in the leader sequence and using a codon optimized copy of G-CSF. Bioinformatic analysis was carried out to propose an explanation for observed effect of mutations on extracellular G-CSF production.

Results

Mutations in the pro-region of the α-mating type (MAT) secretory signal, when placed next to a codon optimized (CO)-GCSF copy, specifically, the Δ57–70 type, led to highest G-CSF titre of 39.4 ± 1.4 mg/L. The enhanced effect of this deletion was also observed when it preceded the WT copy of the gene. Deletion of the 30–43 amino acids in the pro-peptide, fused with the wild type (WT)-GCSF copy, completely diminished G-CSF secretion, while no effect was observed when this deletion was in front of the CO-GCSF construct. Also, Matα:Δ47–49 deletion preceding the WT-GCSF dampened the secretion of this protein, while no effect was seen when this deletion preceded the CO-GCSF copy of the gene. This indicated that faster rates of translation (as achieved through codon optimization) could overcome the control exercised by these segments. The loss of secretion occurring due to Δ30–43 in the WT-GCSF was partially restored (by 60%) when the Δ57–70 was added. The effect of Δ47–49 segment in the WT-GCSF could also be partially restored (by 60%) by addition of Δ57–70 indicating the importance of the 47–49 region. A stimulatory effect of Δ57–70 was confirmed in the double deletion (Matα:Δ57–70;47–49) construct preceding the CO-GCSF. Secondary and tertiary structures, when predicted using I-TASSER, allowed to understand the relationship between structural changes and their impact on G-CSF secretion. The Δ57–70 amino acids form a major part of 3rd alpha-helix in the pre-pro peptide and its distortion increased the flexibility of the loop, thereby promoting its interaction with the cargo protein. A minimum loop length was found to be necessary for secretion. The strict control in the process of secretion appeared to be overcome by changing the secondary structures in the signal peptides. Such fine tuning can allow enhanced secretion of other therapeutics in this expression system.

Conclusions

Among the different truncations (Matα:Δ57–70, Matα:Δ47–49, Matα:Δ30–43, Matα:Δ57–70;30–43, Matα:Δ57–70;47–49) in pro-peptide of α-MAT secretion signal, Matα:Δ57–70 fused to CO-GCSF, led to highest G-CSF titre as compared to other Matα truncations. On the other hand, Matα:Δ30–43 and Matα:Δ47–49 fused to the WT-GCSF dampened the secretion of this protein indicating important role of these segments in the secretion of the cargo protein.
Combination strategies to overcome resistance to the BCL2 inhibitor venetoclax in hematologic malignancies
Authors: Yue XiaoYan , Chen Qingxiao , He JingSong
Published: October 2020

Venetoclax has been approved by the United States Food and Drug Administration since 2016 as a monotherapy for treating patients with relapsed/refractory chronic lymphocytic leukemia having 17p deletion. It has led to a breakthrough in the treatment of hematologic malignancies in recent years. However, unfortunately, resistance to venetoclax is inevitable. Multiple studies confirmed that the upregulation of the anti-apoptotic proteins of the B-cell lymphoma 2 (BCL2) family mediated by various mechanisms, such as tumor microenvironment, and the activation of intracellular signaling pathways were the major factors leading to resistance to venetoclax. Therefore, only targeting BCL2 often fails to achieve the expected therapeutic effect. Based on the mechanism of resistance in specific hematologic malignancies, the combination of specific drugs with venetoclax was a clinically optional treatment strategy for overcoming resistance to venetoclax. This study aimed to summarize the possible resistance mechanisms of various hematologic tumors to venetoclax and the corresponding clinical strategies to overcome resistance to venetoclax in hematologic malignancies.
Correction to: EIF4A3-induced circular RNA MMP9 (circMMP9) acts as a sponge of miR-124 and promotes glioblastoma multiforme cell tumorigenesis
Authors: Wang Renjie , Zhang Sai , Chen Xuyi , Li Nan , Li Jianwei , Jia Ruichao , Pan Yuanqing , Liang Haiqian
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.
Characterization of the serum levels of Meteorin-like in patients with inflammatory bowel disease and its association with inflammatory cytokines
Authors: Gholamrezayi Afsane , Mohamadinarab Maryam , Rahbarinejad Pegah , Fallah Soudabeh , Barez Shekufe Rezghi , Setayesh Leila , Moradi Nariman , Fadaei Reza , Chamani Elham , Tavakoli Tahmine
Published: October 2020

Background

Meteorin-like (Metrnl) is an adipokine with insulin sensitizing and anti-inflammatory properties that has been discovered recently. The relation among Metrnl, Inflammatory Bowel Disease (IBD), and obesity has been unexplored yet.

Methods

The present study was conducted on 54 healthy control, 42 Ulcerative Colitis (UC), and 43 Crohn’s disease (CD) patients who were diagnosed by pathological examination. In all participants, serum levels of adiponectin, Metrnl, interleukin (IL)-6, and Tumor necrosis factor (TNF-α) were measured using ELISA kits.

Results

Metrnl concentration was considerably lower in both UC (85.25 ± 36.55 pg/mL) and CD (76.93 ± 27.92 pg/mL) patients in comparison to control (107.52 ± 35.33 pg/mL). In addition, it was seen that both patient groups have a decreased level of adiponectin compared to the controls. Besides that, the level of IL-6 and TNF-α were significantly greater in the patient groups. Moreover, the result showed that the level of Metrnl is inversely correlated with body mass index (BMI) in the controls and the patients. Metrnl levels are also inversely associated with IL-6, and TNF-α in both of the patient groups.

Conclusions

The current study is the first one reporting the decreased levels of Metrnl in serum among patients with IBD, which is inversely related with BMI, TNF-α, and IL-6. These results suggested a possible relation of Metrnl with the pathogenesis of IBD, particularly through inflammatory process, although further studies are warranted to dissect the possible mechanism.
Recent progress in the development of upconversion nanomaterials in bioimaging and disease treatment
Authors: Liang Gaofeng , Wang Haojie , Shi Hao , Wang Haitao , Zhu Mengxi , Jing Aihua , Li Jinghua , Li Guangda
Published: October 2020

Multifunctional lanthanide-based upconversion nanoparticles (UCNPs), which feature efficiently convert low-energy photons into high-energy photons, have attracted considerable attention in the domain of materials science and biomedical applications. Due to their unique photophysical properties, including light-emitting stability, excellent upconversion luminescence efficiency, low autofluorescence, and high detection sensitivity, and high penetration depth in samples, UCNPs have been widely applied in biomedical applications, such as biosensing, imaging and theranostics. In this review, we briefly introduced the major components of UCNPs and the luminescence mechanism. Then, we compared several common design synthesis strategies and presented their advantages and disadvantages. Several examples of the functionalization of UCNPs were given. Next, we detailed their biological applications in bioimaging and disease treatment, particularly drug delivery and photodynamic therapy, including antibacterial photodynamic therapy. Finally, the future practical applications in materials science and biomedical fields, as well as the remaining challenges to UCNPs application, were described. This review provides useful practical information and insights for the research on and application of UCNPs in the field of cancer.
Direct oral anticoagulant use in left ventricular thrombus
Authors: Ali Zafar , Isom Nicholas , Dalia Tarun , Sami Farhad , Mahmood Uzair , Shah Zubair , Gupta Kamal
Published: October 2020

Left ventricular thrombus (LVT) is associated with a significant risk of ischemic stroke (IS) and peripheral embolization. Societal guidelines recommend the use of warfarin, with direct oral anticoagulants (DOACs) only for patients unable to tolerate warfarin. We studied the natural history of LVT with anticoagulation (AC) with emphasis on comparing warfarin and DOAC use. In this single center study, we identified patients with a confirmed LVT. Type and duration of anticoagulation, INR levels and clinical outcomes (bleeding, ischemic stroke or peripheral embolization, and thrombus resolution) were recorded. LVT was confirmed in a total of 110 patients. Mean age was 59 + 14 years. 79% were men. Underlying etiology was chronic ischemic cardiomyopathy in 58%, non-ischemic cardiomyopathy in 23%. AC was started in 96 (87%) patients. At 1 year follow up, 11 patients (10%) had a stroke while on any AC (2 had hemorrhagic stroke and 9 had IS). Of those with IS, 7 were on warfarin (71% of those had subtherapeutic INR) and 2 patients on DOACs had IS. The 1-year risk of any stroke was 15% in warfarin group (12% risk of ischemic stroke) compared to 6% in the DOACs group (p = 0.33). 37 (63%) patients on warfarin and 18 (53%) on DOACs had resolution of thrombus (p = 0.85). One-year risk of stroke with LVT is high (10%) even with AC. Most patients IS on warfarin had subtherapeutic INR. There was no statistical difference in stroke risk or rate of thrombus resolution between warfarin and DOACs treated patients.
Serum interleukin-6 is an indicator for severity in 901 patients with SARS-CoV-2 infection: a cohort study
Authors: Zhang Jing , Hao Yiqun , Ou Wuling , Ming Fei , Liang Gai , Qian Yu , Cai Qian , Dong Shuang , Hu Sheng , Wang Weida , Wei Shaozhong
Published: October 2020

Background

Interleukin-6 (IL-6) was proposed to be associated with the severity of coronavirus disease 2019 (COVID-19). The present study aimed to explore the kinetics of IL-6 levels, validate this association in COVID-19 patients, and report preliminary data on the efficacy of IL-6 receptor blockade.

Methods

We conducted a retrospective single-institutional study of 901 consecutive confirmed cases. Serum IL-6 concentrations were tested on admission and/or during hospital stay. Tocilizumab was given to 16 patients with elevated IL-6 concentration.

Results

366 patients were defined as common cases, 411 patients as severe, and 124 patients as critical according to the Chinese guideline on diagnosis and treatment of COVID-19. The median concentration of IL-6 was < 1.5 pg/ml (IQR < 1.50–2.15), 1.85 pg/ml (IQR < 1.50–5.21), and 21.55 pg/ml (IQR 6.47–94.66) for the common, severe, and critical groups respectively (P < 0.001). The follow-up kinetics revealed serum IL-6 remained high in critical patients even when cured. An IL-6 concentration higher than 37.65 pg/ml was predictive of in-hospital death (AUC 0.97 [95% CI 0.95–0.99], P < 0.001) with a sensitivity of 91.7% and a specificity of 95.7%. In the 16 patients who received tocilizumab, IL-6 concentrations were significantly increased after administration, and survival outcome was not significantly different from that of propensity-score matched counterparts (n = 53, P = 0.12).

Conclusion

Serum IL-6 should be included in diagnostic work-up to stratify disease severity, but the benefit of tocilizumab needs further confirmation.

Trial registration retrospectively registered.
Anti-Axl antibody treatment reduces the severity of experimental autoimmune encephalomyelitis
Authors: DuBois Juwen C. , Ray Alex K. , Davies Peter , Shafit-Zagardo Bridget
Published: October 2020

Background

Multiple sclerosis is an immune-mediated disease of the central nervous system (CNS) characterized by inflammation, oligodendrocytes loss, demyelination, and damaged axons. Tyro3, Axl, and MerTK belong to a family of receptor tyrosine kinases that regulate innate immune responses and CNS homeostasis. During experimental autoimmune encephalomyelitis (EAE), the mRNA expression of MerTK, Gas6, and Axl significantly increase, whereas Tyro3 and ProS1 remain unchanged. We have shown that Gas6 is neuroprotective during EAE, and since Gas6 activation of Axl may be necessary for conferring neuroprotection, we sought to determine whether α-Axl or α-MerTK antibodies, shown by others to activate their respective receptors in vivo, could effectively reduce inflammation and neurodegeneration.

Methods

Mice received either α-Axl, α-MerTK, IgG isotype control, or PBS before the onset of EAE symptoms. EAE clinical course, axonal damage, demyelination, cytokine production, and immune cell activation in the CNS were used to determine the severity of EAE.

Results

α-Axl antibody treatment significantly decreased the EAE clinical indices of female mice during chronic EAE and of male mice during both acute and chronic phases. The number of days mice were severely paralyzed also significantly decreased with α-Axl treatment. Inflammatory macrophages/microglia and the extent of demyelination significantly decreased in the spinal cords of α-Axl-treated mice during chronic EAE, with no differences in the production of pro-inflammatory cytokines. α-MerTK antibody did not influence EAE induction or progression.

Conclusion

Our data suggests that the beneficial effect of Gas6/Axl signaling observed in mice administered with Gas6 can be partially preserved by administering an activating α-Axl antibody, but not α-MerTK.
Protocol of a study investigating breath-hold techniques for upper-abdominal radiation therapy (BURDIE): addressing the challenge of a moving target
Authors: Farrugia Briana , Khor Richard , Foroudi Farshad , Chao Michael , Knight Kellie , Wright Caroline
Published: October 2020

Background

Radiation therapy to upper abdominal sites is technically challenging due to motion of tumors and surrounding organs resulting from normal respiration. Breath-hold, using an Active Breathing Coordinator is one strategy used to reduce motion in these tumor sites. Though widely used, no studies have prospectively compared the different breath-hold techniques (inspiration, deep-inspiration and expiration) using ABC in the same patient cohort.

Methods

Patients planned for radiation therapy to upper abdominal tumors are invited to participate in this prospective study. Participants attempt three breath hold techniques: inspiration, deep-inspiration and expiration breath-hold, in random order. kV fluoroscopy images of the dome of diaphragm are taken of five consecutive breath-holds in each technique. Reproducibility and stability of tumour position are measured, and used to select the technique with which to proceed to planning and treatment. Reproducibility at planning and each treatment fraction is measured, along with breath hold time, treatment efficiency and patient experience.

Discussion

The screening method was validated after the first three participants. This screening process may be able to select the best breath-hold technique for an individual, which may lead to improved reproducibility. The screening process is being piloted as a prospective clinical trial.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR): 12618001691235. Registered 12th October 2018. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376109&isReview=true.
Disordered leptin and ghrelin bioactivity in adolescent idiopathic scoliosis (AIS): a systematic review and meta-analysis
Authors: Wang Qi , Wang Chi , Hu Wenhao , Hu Fanqi , Liu Weibo , Zhang Xuesong
Published: October 2020

Background

Adolescents with scoliosis consistently demonstrate lower body weight, lean muscle mass, and bone mineral density than healthy adolescent counterparts. Recent studies have focused on understanding how leptin and ghrelin signaling may play a role in adolescent idiopathic scoliosis (AIS). In our current study, we aim to evaluate the serum levels of leptin, soluble leptin receptor (sOB-R), and ghrelin in AIS patients through systematic review and meta-analysis.

Methods

We conducted our systematic review by searching the keywords in online databases including PubMed, Embase, Cochrane, Elsevier, Springer, and Web of Science from the time of database inception to January 2020. Inclusion criteria were studies that measure leptin, soluble leptin receptor (sOB-R), and ghrelin levels in AIS patients. Selection of studies, assessment of study quality, and data extraction were performed by two reviewers independently. Then, data was analyzed to calculate the mean difference and 95% confidence interval (CI).

Results

Seven studies concerning leptin/sOB-R and three studies concerning ghrelin were qualified for meta-analysis (one study concerning both leptin and ghrelin). Serum leptin of patients with AIS were significantly lower when compared with healthy controls, with the weighted mean difference (WMD) of − 0.95 (95% CI − 1.43 to − 0.48, p < 0.0001) after reducing the heterogeneity using six studies for meta-analysis, while sOB-R and ghrelin level was significantly higher in AIS group when compared with control group, with the WMD of 2.64 (95% CI 1.60 to 3.67, p < 0.001) and 1.42 (95% CI 0.48 to 2.35, p = 0.003), respectively.

Conclusion

Our current meta-analysis showed that serum level of leptin in AIS patients was significantly lower when compared with control subjects, while serum sOB-R and ghrelin levels were significantly higher in AIS patients. More clinical studies are still required to further validate the predictive value of leptin or ghrelin for the curve progression for AIS patients.
Metaphyseal anchoring short stem hip arthroplasty provides a more physiological load transfer: a comparative finite element analysis study
Authors: Yan Shuang G. , Chevalier Yan , Liu Fanxiao , Hua Xingyi , Schreiner Anna , Jansson Volkmar , Schmidutz Florian
Published: October 2020

Background

Short stem total hip arthroplasty (SHA) preserves femoral bone stock and is supposed to provide a more natural load transfer compared to standard stem total hip arthroplasty (THA). As comparative biomechanical reference data are rare we used a finite element analysis (FEA) approach to compare cortical load transfer after implantations of a metaphyseal anchoring short and standard stem in native biomechanical femora.

Methods

The subject specific finite element models of biomechanical femora, one native and two with implanted metaphyseal anchoring SHA (Metha, B. Braun Aesculap) and standard THA (CLS, Zimmer-Biomet), were generated from computed tomography datasets. The loading configuration was performed with an axial force of 1400 N. Von Mises stress was used to investigate the change of cortical stress distribution.

Results

Compared to the native femur, a considerable reduction of cortical stress was recorded after implantation of SHA and standard THA. The SHA showed less reduction proximally with a significant higher metaphyseal cortical stress compared to standard THA. Moreover, the highest peak stresses were observed metaphyseal for the SHA stem while for the standard THA high stress pattern was observed more distally.

Conclusions

Both, short and standard THA, cause unloading of the proximal femur. However, the metaphyseal anchoring SHA features a clearly favorable pattern in terms of a lower reduction proximally and improved metaphyseal loading, while standard THA shows a higher proximal unloading and more distal load transfer. These load patterns implicate a reduced stress shielding proximally for metaphyseal anchoring SHA stems and might be able to translate in a better bone preservation.
External female genitalia of Triatoma jatai, Triatoma costalimai and Triatoma williami (Hemiptera: Reduviidae: Triatominae)
Authors: Teves Simone Caldas , Gonçalves Teresa Cristina Monte , de Freitas Simone Patrícia Carneiro , Lopes Catarina Macedo , Carbajal-de-la-Fuente Ana Laura , dos Santos-Mallet Jacenir Reis
Published: October 2020

Background

Taxonomic identification of triatomines is generally performed based on aspects of their external morphology. However, the use of a multidisciplinary approach, considering morphological aspects of the external genitalia, morphometry, genetics, and phylogeography has been suggested, especially for similar and/or cryptic species. The rupestral species Triatoma jatai Gonçalves et al., 2013, Triatoma costalimai Verano & Galvão, 1959 and Triatoma williami Galvão et al., 1965, which are morphologically similar, have been found naturally infected with Trypanosoma cruzi (Chagas, 1909) in wild, peridomestic, and intradomestic environments, representing a risk of new outbreaks of Chagas disease. This study presents morphological description complementation of these species, with an emphasis on the structures of the female external genitalia, using scanning electron microscopy.

Methods

The females of T. jatai and T. costalimai (n = 10 of each) were captured in the Brazilian municipalities of Paranã and Aurora do Tocantins and were identified with the use of a dichotomous key for the Matogrossensis subcomplex. Females of T. williami (n = 5), were obtained from a laboratory colony. The females were cut transversely at the sixth abdominal segment and examined under scanning electron microscopy (SEM) at the Oswaldo Cruz/Fiocruz Institute Electronic Microscopy Platform.

Results

It was possible to differentiate the three species based on the characteristics of urotergites VII, VIII and IX and urosternite VII, as well as the genital plaques, gonocoxites, and gonapophyses. To our knowledge, morphological differences in the spines present on gonapophysis 8 in triatomines are described here for the first time.

Conclusions

The results show that external genitalia of females are useful structures to differentiate T. costalimai, T. jatai and T. williami. SEM analysis contributes to and corroborates, together with other tools morphological and molecular, the distinction of the three species.
A novel dynamic source routing (DSR) protocol based on minimum execution time scheduling and moth flame optimization (MET-MFO)
Authors: Almazok Salem A. , Bilgehan Bülent
Published: October 2020

In general, the conventional routing approaches in mobile ad hoc networks (MANETs) provide a route between the source and the target with a minimum hop count. Dynamic source routing (DSR) as a typical prototype of routing protocols relies on the minimum hop count parameter to provide the path without considering any other factors such as energy consumption and node energy level, which significantly affect the routing algorithm performance. To enhance the performance of the DSR, a novel and efficient routing mechanism based on a hybrid approach using the minimum execution time (MET) scheduling and moth flame optimization (MFO) scheme is proposed. This hybridization version of DSR is called the (MET-MFODSR) algorithm, and it aims to improve the routing mechanism through establishing an optimal route with minimum energy consumption, which increases the network lifetime and reduces route failure issues. The proposed MET-MFODSR protocol is implemented using the MATLAB platform, analyzed and evaluated in different simulation environments. The simulation results demonstrate that the suggested routing algorithm is applicative and practicable, and its performance exceeds the performance of the existing Bee DSR (BEEDSR) and Bee-inspired protocol (BeeIP) algorithms.
The solvability of a kind of generalized Riemann–Hilbert problems on function spaces $H_{\ast }$
Authors: Li Pingrun
Published: October 2020

In this paper, we study a kind of generalized Riemann–Hilbert problems (R-HPs) with several unknown functions in strip domains. We mainly discuss methods of solving R-HPs with two unknown functions and obtain general solutions and conditions of solvability on function spaces $H_{\ast }$

H
∗

. At the end of this paper, we consider in detail the behavior of the solution at ∞ and in different domains. Thus the results in this paper generalize and improve the theory of the classical Riemann–Hilbert problems.
Approximate solutions for a fractional hybrid initial value problem via the Caputo conformable derivative
Authors: Amara Abdelkader , Etemad Sina , Rezapour Shahram
Published: October 2020

Our main purpose in this work is to derive an existence criterion for a Caputo conformable hybrid multi-term integro-differential equation equipped with initial conditions. In this way, we consider a partially ordered Banach space, and, by applying the lower solution property, the existence and successive approximations of solutions for the mentioned hybrid initial problem are investigated. Eventually, we formulate an illustrative example for this hybrid IVP to support our findings from a numerical point of view. Moreover, we plot the sequence of the obtained approximate solutions for different values of noninteger orders.
Fibroblast-like cells change gene expression of bone remodelling markers in transwell cultures
Authors: Hartmann Eliza S. , Schluessel Sabine , Köhler Miriam I. , Beck Felicitas , Redeker Julia I. , Summer Burkhard , Schönitzer Veronika , Fottner Andreas , Mayer-Wagner Susanne
Published: October 2020

Introduction

Periprosthetic fibroblast-like cells (PPFs) play an important role in aseptic loosening of arthroplasties. Various studies have examined PPF behavior in monolayer culture systems. However, the periprosthetic tissue is a three-dimensional (3D) mesh, which allows the cells to interact in a multidirectional way. The expression of bone remodeling markers of fibroblast-like cells in a multilayer environment changes significantly versus monolayer cultures without the addition of particles or cytokine stimulation. Gene expression of bone remodeling markers was therefore compared in fibroblast-like cells from different origins and dermal fibroblasts under transwell culture conditions versus monolayer cultures.

Methods

PPFs from periprosthetic tissues (n = 12), osteoarthritic (OA) synovial fibroblast-like cells (SFs) (n = 6), and dermal fibroblasts (DFs) were cultured in monolayer (density 5.5 × 103/cm2) or multilayer cultures (density 8.5 × 105/cm2) for 10 or 21 days. Cultures were examined via histology, TRAP staining, immunohistochemistry (anti-S100a4), and quantitative real-time PCR.

Results

Fibroblast-like cells (PPFs/SFs) and dermal fibroblasts significantly increased the expression of RANKL and significantly decreased the expression of ALP, COL1A1, and OPG in multilayer cultures. PPFs and SFs in multilayer cultures further showed a higher expression of cathepsin K, MMP-13, and TNF-α. In multilayer PPF cultures, the mRNA level of TRAP was also found to be significantly increased.

Conclusion

The multilayer cultures are able to induce significant expression changes in fibroblast-like cells depending on the nature of cellular origin without the addition of any further stimulus. This system might be a useful tool to get more in vivo like results regarding fibroblast-like cell cultures.