bluuebunny/crossref_metadata_2025 huggingface dataset:
Curcumin Affects Parkinson Protein 7 (PARK7; DJ-1) Expression and Regulates Proliferation and Apoptosis of Breast Cancer Cells by Up-Regulating miR-203
Authors: Wang Lu , Shen Jianglun , Li Ning , Zhang Yang , Hu Feng , Dai Hao , Cai Haifeng , Yan Jinyin
Published: August 2021

PTEN can inhibit PI3 K/AKT signaling pathway and DJ-1 negatively regualtes PTEN. Curcumin (Cur) regulates PTEN-PI3 K/AKT pathway. Bioinformatics analysis showed a targeting relationship between miR-203 and DJ-1, but it is unclear whether Cur regulates DJ-1-PTEN/PI3 K/AKT pathway through
miR-203. We assessed Cur’s role in breast cancer cells. MCF-10A and MDA-MB-231 cells were cultured and expression of miR-203, DJ-1 and PTEN mRNA was measured by qRT-PCR. MDA-MB-231 cells were treated with 0, 10 μM Cur followed by analysis cell proliferation by CCK-8 assay,
cell apoptosis by flow cytometry, miR-203, DJ-1 and PTEN mRNA level by qRT-PCR. MDA-MB-231 cells were divided into 3 groups: 0 μM, 10 μM Cur+miR-NC treatment group, 10 μM+miR-203 inhibitor group to measure cell apoptosis and proliferation. Compared with MCF-10A
cells, miR-203 and DJ-1 mRNA in MDA-MB-231 cells was significantly upregulated and PTEN mRNA expression was decreased. Cur treatment significantly decreased cell proliferation, promoted caspase-3 activity and cell apoptosis, as well as elevated miR-203 and PTEN mRNA level and decreased DJ-1
mRNA level. miR-203 inhibitor transfection can antagonize Cur’s effect on upregulation of miR-203, increase DJ-1 expression, decrease PTEN expression, enhance PI3 K/AKT pathway activity, and antagonize Cur’s anti-tumor effect. Curcumin increases miR-203 expression, down-regulates
DJ-1 expression, affects PTEN-PI3 K/AKT pathway activity, and play an anti-tumor effect through inhibiting breast cancer cell proliferation and promoting apoptosis.
Impacts of ocean currents on the South Indian Ocean extratropical storm track through the relative wind effect
Authors: Seo Hyodae , Song Hajoon , O’Neill Larry W. , Mazloff Matthew R. , Cornuelle Bruce D.
Published: August 2021

This study examines the role of the relative wind (RW) effect (wind relative to ocean current) in the regional ocean circulation and extratropical storm track in the South Indian Ocean. Comparison of two high-resolution regional coupled model simulations with/without the RW effect reveals that the most conspicuous ocean circulation response is the significant weakening of the overly energetic anticyclonic standing eddy off Port Elizabeth, South Africa, a biased feature ascribed to upstream retroflection of the Agulhas Current (AC). This opens a pathway through which the AC transports the warm and salty water mass from the subtropics, yielding marked increases in sea surface temperature (SST), upward turbulent heat flux (THF), and meridional SST gradient in the Agulhas retroflection region. These thermodynamic and dynamic changes are accompanied by the robust strengthening of the local low-tropospheric baroclinicity and the baroclinic wave activity in the atmosphere. Examination of the composite lifecycle of synoptic-scale storms subjected to the high THF events indicates a robust strengthening of the extratropical storms far downstream. Energetics calculations for the atmosphere suggest that the baroclinic energy conversion from the basic flow is the chief source of increased eddy available potential energy, which is subsequently converted to eddy kinetic energy, providing for the growth of transient baroclinic waves. Overall, the results suggest that the mechanical and thermal air-sea interactions are inherently and inextricably linked together to substantially influence the extratropical storm tracks in the South Indian Ocean.
Direct Solar Viewing Calibration Concept for Future CERES-, GERB-, or Libera-Type Earth Orbital Climate Missions
Authors: Matthews G.
Published: August 2021

Better predictions of global warming can be enabled by tuning legacy and current computer simulations to Earth radiation budget (ERB) measurements. Since the 1970s, such orbital results exist, and the next-generation instruments such as one called “Libera” are in production. Climate communities have requested that new ERB observing system missions like these have calibration accuracy obtaining significantly improved calibration SI traceability and stability. This is to prevent untracked instrument calibration drifts that could lead to false conclusions on climate change. Based on experience from previous ERB missions, the alternative concept presented here utilizes directly viewing solar calibration, for cloud-size Earth measurement resolution at <1% accuracy. However, it neglects complex already used calibration technology like solar diffusers and onboard lights, allowing new lower cost/risk unconsidered spectral characterizing concepts to be introduced for today’s technology. Also in contrast to near future ERB concepts already being produced, this enables in-flight wavelength dependent calibration of Earth-observing telescopes using direct solar views, through narrowband filters continuously characterized on-orbit.
Snowfall Model Validation Using Surface Observations and an Optimal Estimation Snowfall Retrieval
Authors: Hellmuth Franziska , Kokkvoll Engdahl Bjørg Jenny , Storelvmo Trude , David Robert O. , Cooper Steven J.
Published: August 2021

In the winter, orographic precipitation falls as snow in the mid- to high latitudes where it causes avalanches, affects local infrastructure, or leads to flooding during the spring thaw. We present a technique to validate operational numerical weather prediction model simulations in complex terrain. The presented verification technique uses a combined retrieval approach to obtain surface snowfall accumulation and vertical profiles of snow water at the Haukeliseter test site, Norway. Both surface observations and vertical profiles of snow are used to validate model simulations from the Norwegian Meteorological Institute’s operational forecast system and two simulations with adjusted cloud microphysics. Retrieved surface snowfall is validated against measurements conducted with a double-fence automated reference gauge (DFAR). In comparison, the optimal estimation snowfall retrieval produces +10.9% more surface snowfall than the DFAR. The predicted surface snowfall from the operational forecast model and two additional simulations with microphysical adjustments (CTRL and ICE-T) are overestimated at the surface with +41.0%, +43.8%, and +59.2%, respectively. Simultaneously, the CTRL and ICE-T simulations underestimate the mean snow water path by −1071.4% and −523.7%, respectively. The study shows that we would reach false conclusions only using surface accumulation or vertical snow water content profiles. These results highlight the need to combine ground-based in situ and vertically profiling remote sensing instruments to identify biases in numerical weather prediction.
Universal Design for Learning
Authors: Levey Sandra
Published: August 2021

This review presents the Universal Design Learning (UDL) approach to education. Classrooms have become increasingly diverse, with second language learners, students with disabilities, and students with differences in their perception and understanding information. Some students learn best through listening, while others learn best when presented with visual information. Given the increased number of new language learners across the world, the UDL approach allows successful learning for all students. UDL has allowed students to acquire information more effectively. UDL provides guidance to educators that is especially valuable for the diversity of classrooms and the diversity in modalities in learning,
Robotic grasping method of bolster spring based on image-based visual servoing with YOLOv3 object detection algorithm
Authors: Li Dafa , Liu Huanlong , Wei Tao , Zhou Jianyi
Published: August 2021

In this paper, to address the problem of automatic positioning and grasping of bolster spring with complex geometric features and cluttered background, a novel image-based visual servoing (IBVS) control method based on the corner points features of YOLOv3 object detection bounding box is proposed and applied to the robotic grasping system of bolster spring. The YOLOv3 object detection model is used to detect and position the bolster spring and then based on the corner points features of the bolster spring bounding box, the IBVS controller is designed to drive the end effector of the robot to the desired pose. This method adopts the approach-align-grasp control strategy to achieve the grasping of the bolster spring, which is very robust to the calibration parameter errors of the camera and the robot model. With the help of Robotics and Machine Vision Toolboxes in Matlab, IBVS simulation analysis based on feature points is carried out. The results show that it is reasonable to use the corner points of the object detection bounding box as image features under the initial pose where the image plane is parallel to the object plane. The positioning and grasping experiments are conducted on the robotic grasping platform of bolster spring. The results show that this method is effective for automatic positioning and grasping of bolster spring with complex geometric features and cluttered background, and it has strong robustness to the change of illumination.
On the estimation of optimal state-of-charge trajectory for plug-in hybrid electric buses using trip information
Authors: Sina Naser , Esfahanian Vahid , Reza Hairi Yazdi Mohammad
Published: August 2021

Plug-in hybrid electric buses are a viable solution to increase the fuel economy. In this framework, precise estimation of optimal state-of-charge trajectory along the upcoming driving cycle appears to play a pivotal role in the way to approach the globally optimal fuel economy. This paper aims to conduct a parametric study on the key factors affecting the estimation of optimal state-of-charge trajectory, including trip information availability and trip segment distance, and to provide a guideline for the design and implementation of predictive energy management systems. To accomplish this, the dynamic programming algorithm is employed to obtain the solution of optimal control problem for the sampled driving cycles in a particular bus route. A large database comprising of driving features of the cycles and the optimal solution is developed which then is used to construct a neural network based estimator for obtaining the optimal state-of-charge trajectory. The main results show promising performance of the proposed method with about 76% reduction in the root mean square error of the estimated trajectory comparing to the linear state-of-charge trajectory assumption. Moreover, the robustness of the estimator is verified through simulation and it is observed that appropriate choice of trip segment distance is vital to improve the estimation accuracy, especially in case of uncertain prediction of trip information.
Transparency in Online Pedagogy: A Critical Analysis of Changing Modalities
Authors: Kirschner Julianna
Published: August 2021

As a result of the coronavirus disease 2019 (COVID-19) pandemic, college and university faculty have been tasked with moving their courses toward online modalities with minimal notice. This environment challenged faculty in unique ways, but the need for transparency and communication became more important than ever. To improve the student experience, faculty should consider adapting their strategies to accommodate the online space. Using critical analysis, this piece addresses specific steps faculty can take to improve the transition toward online teaching. These steps include increased access to the instructor and online learning materials, adapting course materials and syllabi, and acceptance of perceived failure.
A novel graded auxetic honeycomb core model for sandwich structures with increasing natural frequencies
Authors: Zamani Mohammad Hossein , Heidari-Rarani Mohammad , Torabi Keivan
Published: August 2021

A novel angle graded auxetic honeycomb (AGAH) core is designed for sandwich structures in the present study. The angle of the cells is varied through the thickness of the AGAH core using linear functions. Therefore, the thickness of the cell walls is kept constant along the gradation of the cell angle, and the length of the cell walls is changed through the core thickness as the result of angle variation. New analytical relations are proposed to predict the equivalent elastic properties of the AGAH core. The performance of the new proposed core is analytically assessed for the vibrational behavior of a sandwich plate. The governing equations are deduced adopting Hamilton’s principle under the assumption of quasi-3D exponential plate theory. Three-dimensional finite element (3D-FE) simulation is accomplished to verify the analytical results of the vibrational response of the sandwich structure. The influence of variation of the cell wall, the cell angle and cell aspect ratio of AGAH core, and geometric parameters of the sandwich structure are investigated on the vibration response of the sandwich panel. The present graded design of the auxetic honeycomb enhances the specific stiffness (i.e., stiffness to density ratio) and consequently increases the natural frequencies of sandwich structures with this type of core.
Management of small perforated corneal ulcers: Training model in mammalian eye to enhance surgical skills of residents
Authors: Bafna Rahul Kumar , Tripathi Manasi , Asif Mohamed Ibrahime , Agarwal Rinky , Lata Suman , Kumar Sushil , Sharma Namrata
Published: August 2021

Purpose:

To demonstrate a training technique on the mammalian eye for optimum Cyanoacrylate Tissue adhesive application in cases of perforated corneal ulcers.

Methods:

A full-thickness defect simulating a perforation was created on the goat’s eye cornea to teach the technique of cyanoacrylate glue application in cases of corneal perforations to novice surgeons.

Results:

This training model on the mammalian eye was tested by 10 residents at our centre. All the 10 candidates involved in our series were newly joined Cornea fellows with proficient skill in cataract surgeries and minor ophthalmic procedures such as suture removal, chalazion excision, pterygium removal and administration of an intravitreal injection. None of the candidates had prior experience of corneal surgeries. Each resident made an average of 4.4 attempts to seal the corneal defect, obtain a regular corneal surface and form the anterior chamber.

Conclusion:

This training model helps in mastering one of the skills of corneal surgeries.
The Facility Infection Risk Estimator™: A web application tool for comparing indoor risk mitigation strategies by estimating airborne transmission risk
Authors: Harmon Marcel , Lau Josephine
Published: August 2021

The COVID-19 pandemic created needs for (a) estimating the existing airborne risk of infection from SARS-CoV-2 in existing facilities and new designs and (b) estimating and comparing the impacts of engineering and behavioural strategies for contextually reducing that risk. This paper presents the development of a web application to meet these needs, the Facility Infection Risk Estimator™, and its underlying Wells–Riley based model. The model specifically estimates (a) the removal efficiencies of various settling, ventilation, filtration and virus inactivation strategies and (b) the associated probability of infection, given the room physical parameters and number of individuals infected present with either influenza or SARS-CoV-2. A review of the underlying calculations and associated literature is provided, along with the model's validation against two documented spreading events. The error between modelled and actual number of additional people infected, normalized by the number of uninfected people present, ranged from roughly –18.4% to +9.7%. The more certain one can be regarding the input parameters (such as for new designs or existing buildings with adequate field verification), the smaller these normalized errors will be, likely less than ±15%, making it useful for comparing the impacts of different risk mitigation strategies focused on airborne transmission.
Direct Democracy and Party Membership: Testing the Role of Political Efficacy
Authors: Chang Wen-Chun
Published: August 2021

The declines in political party memberships along with an increase in direct democracy have drawn numerous scholarly discussions. Previous literature has explored the relationship between direct democracy and party membership, but the role of political efficacy in shaping this relationship has not been systematically examined. In particular, direct democracy can increase political efficacy by enhancing citizens’ civic skills and perceptions about government responsiveness and indirectly raise citizens’ interests in joining political parties. Using the structural equation model, this study shows that political efficacy strongly correlates with direct democracy and plays a significant role in influencing the effect of direct democracy on party membership. Moreover, results from the bootstrap mediation test of examining potential causal inferences suggest that there are distinct differences in the indirect effects of direct democracy mediated by internal efficacy and external efficacy on party membership.
Emotional Intelligence, Organizational Social Architecture, and Black Male Leadership
Authors: Rudel Enin M. , Derr Brandi , Ralston Miranda , Williams Terrence B. , Young Aprille
Published: August 2021

The Problem

The leadership of Black male leaders is an under-studied topic in the leadership literature and more so in the field of human resource development. Moreover, traditional and contemporary leadership theories are universalized and have not adequately captured social and emotional issues encountered by leaders within their social identity location. A closer examination of this phenomenon is needed to close the gap in the human resource development literature as well as contemporary leadership theory.

The Solution

A qualitative study was used to examine the experiences of Black male leaders in an organizational setting using the frameworks of emotional intelligence and social architecture. Findings suggest that emotional intelligence explains why Black male leaders desire mentorship, need increased organizational support for psychological safety, use specialized strategies to deal with social and emotional distress, face barriers to acculturation into the workplace culture, draw on authentic leadership skills to face obstructions to leadership, and use code switching to navigate multiple identities. Recommendations are made for more inclusive mentoring programs that consider the needs of this underrepresented group.

The Stakeholders

HRD researchers, scholars, educators, practitioners, organizational leaders and others involved in diversity, equity, and inclusion work.
Improvements in lung function with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler versus dual therapies in patients with COPD: a sub-study of the ETHOS trial
Authors: Rabe Klaus F. , Martinez Fernando J. , Singh Dave , Trivedi Roopa , Jenkins Martin , Darken Patrick , Aurivillius Magnus , Dorinsky Paul
Published: August 2021

Background:

In the phase III, 52-week ETHOS study in patients with moderate to very severe chronic obstructive pulmonary disease (COPD), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF), at two inhaled corticosteroid dose levels, resulted in significantly lower moderate/severe exacerbation rates versus glycopyrrolate/formoterol fumarate (GFF) and budesonide/formoterol fumarate (BFF). Here, we report results from the ETHOS pulmonary function test (PFT) sub-study, which assessed lung function in a subset of ETHOS patients.

Methods:

ETHOS (NCT02465567) was a randomized, double-blind, multi-center, parallel-group study in patients with moderate to very severe COPD who had experienced ⩾1 moderate/severe exacerbation in the previous year. Patients received BGF 320/18/9.6 µg, BGF 160/18/9.6 μg, GFF 18/9.6 µg, or BFF 320/9.6 µg twice daily via a single metered dose Aerosphere inhaler for 52 weeks. A subset of patients participated in the 4-hour PFT sub-study; primary endpoints were change from baseline in morning pre-dose trough forced expiratory volume in one second (FEV1) versus GFF and FEV1 area under the curve from 0 to 4 hours (AUC0–4) versus BFF at week 24.

Results:

The PFT modified intent-to-treat population included 3088 patients (mean age 64.4 years; mean reversibility post-albuterol 16.7%; mean post-albuterol FEV1% predicted 42.8). BGF 320/18/9.6 µg and 160/18/9.6 µg significantly improved morning pre-dose trough FEV1 at week 24 versus GFF ( p ⩽ 0.0035 for both). Improvements in trough FEV1 were also observed at week 52 for BGF 320/18/9.6 µg and 160/18/9.6 µg versus GFF ( p ⩽ 0.0005 for both). For FEV1 AUC0–4 at week 24, BGF 320/18/9.6 µg and 160/18/9.6 µg showed significant improvements versus BFF ( p < 0.0001 for both). Improvements were maintained at week 52 ( p < 0.0001).

Conclusions:

BGF 320/18/9.6 µg and 160/18/9.6 µg significantly improved trough FEV1 versus GFF and FEV1 AUC0–4 versus BFF at week 24. The lung function benefits with both doses of BGF were maintained following 52 weeks of treatment. The reviews of this paper are available via the supplemental material section.
Pain and Opioid Use: Evidence for Integrating Acupuncture Into Treatment Planning
Authors: Sommers Elizabeth , Vinjamury Sivarama Prasad , Noborikawa Jennifer
Published: August 2021

The epidemics of pain and opioid use pose unique challenges. Comprehensive approaches are required to address minds, bodies and spirits of individuals who live with pain and/or opioid use. The lack of an effective “quick fix” for either condition necessitates developing effective, innovative and multi-disciplinary avenues for treatment. This analytic article reviews epidemiological and demographic factors associated with pain and with opioid use and additional challenges posed by the Covid-19 epidemic. Several large-scale studies and meta-analyses have examined the role of acupuncture as a nonpharmacological approach to pain management as well as a component of comprehensive strategies to address opioid use disorder. We review and describe these in the context of safety, effectiveness, access and cost-related factors. With one in four U.S. hospitals as well as 88% of Veterans Health Administration facilities incorporating acupuncture, the feasibility of mobilizing and scaling up these treatment resources is being developed and demonstrated. We also identify potential facilitators and barriers to implementing acupuncture treatment. As part of a multi-disciplinary approach to pain management and/or opioid use disorder, we suggest that integrating acupuncture into treatment protocols may represent a viable strategy that is based on and consistent with public health principles.
A QuantCrit Analysis of Context, Discipline, Special Education, and Disproportionality
Authors: Cruz Rebecca A. , Kulkarni Saili S. , Firestone Allison R.
Published: August 2021

Using a dis/ability critical race theory (DisCrit) and critical quantitative (QuantCrit) lens, we examine disproportionate application of exclusionary discipline on multiply marginalized youth, foregrounding systemic injustice and institutionalized racism. In doing so, we examined temporal-, student-, and school-level factors that may result in exclusion and othering (i.e., placing into special education and punishing with out-of-school suspensions) within one school district. We frame this study in DisCrit and QuantCrit frameworks to connect data-based decision making to sociocultural understandings of the ways in which schools use both special education and discipline to simultaneously provide and limit opportunities for different student groups. Results showed a complex interconnectedness between student sociodemographic labels (e.g., gender, race, and socioeconomic status) and factors associated with both special education identification and exclusionary discipline. Our findings suggest that quantitative studies lacking in-depth theoretical justification may perpetuate deficit understandings of the racialization of disability and intersections with exclusionary discipline.
Next-Generation Sequencing-Based Monitoring of Circulating Tumor DNA Reveals Clonotypic Heterogeneity in Untreated PTCL
Authors: Miljkovic Milos D , Melani Christopher , Pittaluga Stefania , Lakhotia Rahul , Lucas Andrea Nicole , Jacob Allison P , Yusko Erik , Jaffe Elaine S. , Wilson Wyndham H. , Roschewski Mark J.
Published: August 2021

Peripheral T-cell lymphomas (PTCL) have marked biologic and clinical heterogeneity, which confounds treatment decisions. Advances in circulating tumor DNA (ctDNA) assays employing next generation sequencing (NGS) has improved the detection of molecular relapse and driver mutations in diffuse large B-cell lymphoma, and highlight the potential utility of ctDNA across lymphomas. We investigated NGS-based monitoring of T-cell receptor (TCR) sequences in PTCL patients undergoing frontline treatment (NCT00001337). Of 45 patients, 34 (76%) had tumor-specific clonotypes of the TCR β or ɣ genes identified, which included 18 (86%) from baseline tissue and 16 (67%) from baseline serum. Twenty-five (74%) patients had both TCRβ and TCRɣ clonotypes, 23 (68%) patients had more than one TCRɣ clonotype, and 4 (9%) had multiple TCRβ or TCRɣ clonotypes, demonstrating significant intra-patient clonotypic heterogeneity. Among 24 patients with available serial serum samples during treatment, 9 (38%) cleared ctDNA after 2 cycles of therapy, and 11 (46%) patients had detectable ctDNA at the end of treatment. Patients with detectable ctDNA after therapy showed a trend towards worse survival. Notably, two patients with persistently detectable ctDNA after therapy remain in remission with 10-years of follow-up. Clonotypic heterogeneity in tumors and persistence despite long-term remission suggests variability in oncological potential.
Tisagenlecleucel immunogenicity in relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma
Authors: Thudium Mueller Karen , Grupp Stephan A. , Maude Shannon L. , Levine John E. , Pulsipher Michael A. , Boyer Michael W. , August Keith J. , Myers G. Doug , Tam Constantine S. , Jaeger Ulrich , Foley Stephen Ronan , Borchmann Peter , Schuster Stephen J. , Waller Edmund K. , Awasthi Rakesh , Potthoff Bernd , Warren Andy , Waldron Edward R. , McBlane Fraser , Chassot-Agostinho Andrea , Laetsch Theodore W.
Published: August 2021

Tisagenlecleucel is indicated for pediatric and young adult patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) and adult patients with r/r diffuse large B-cell lymphoma (DLBCL). The tisagenlecleucel chimeric antigen receptor (CAR) contains a murine single-chain variable fragment domain; we examined the effects of humoral and cellular immune responses to tisagenlecleucel on clinical outcomes using 2 validated assays. Data were pooled from the ELIANA (registered at www.clinicaltrials.gov as #NCT02435849) and ENSIGN (#NCT02228096) trials in r/r B-ALL (N = 143) and the JULIET trial (#NCT02445248) in r/r DLBCL (N = 115). Humoral responses were determined by flow cytometric measurement of anti-murine CAR19 (mCAR19) antibodies in serum. Cellular responses were determined using T-cell production of interferon-γ in response to 2 different pools of mCAR19 peptides. Pretreatment anti-mCAR19 antibodies were detected in 81% of patients with r/r B-ALL and 94% of patients with r/r DLBCL. Posttreatment anti-mCAR19 antibodies were higher than patient-specific baseline in 42% of r/r B-ALL and 9% of r/r DLBCL patients. Pretreatment and posttreatment anti-mCAR19 antibodies did not affect tisagenlecleucel cellular kinetics, including maximum concentration and persistence (r2 < 0.05), clinical response (day-28 response, duration of response, and event-free survival), and safety. T-cell responses were consistent over time, with net responses <1% at baseline and posttreatment time points in a majority of patients and no effect on transgene expansion or persistence or outcomes. Presence of baseline and/or posttreatment anti-mCAR19 antibodies or T-cell responses did not alter the activity of tisagenlecleucel in patients with r/r B-ALL or r/r DLBCL.
Modified EASIX predicts severe cytokine release syndrome and neurotoxicity after chimeric antigen receptor T cells
Authors: Pennisi Martina , Sanchez-Escamilla Miriam , Flynn Jessica R. , Shouval Roni , Alarcon Tomas Ana , Silverberg Mari Lynn , Batlevi Connie , Brentjens Renier J. , Dahi Parastoo B. , Devlin Sean M. , Diamonte Claudia , Giralt Sergio , Halton Elizabeth F. , Jain Tania , Maloy Molly , Mead Elena , Palomba Maria Lia , Ruiz Josel , Santomasso Bianca , Sauter Craig S. , Scordo Michael , Shah Gunjan L. , Park Jae H. , Yanez San Segundo Lucrecia , Perales Miguel-Angel
Published: August 2021

Patients who develop chimeric antigen receptor (CAR) T-cell–related severe cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) exhibit hemodynamic instability and endothelial activation. The EASIX (Endothelial Activation and Stress Index) score (lactate dehydrogenase [LDH; U/L] × creatinine [mg/dL]/platelets [PLTs; 109 cells/L]) is a marker of endothelial damage that correlates with outcomes in allogeneic hematopoietic cell transplantation. Elevated LDH and low PLTs have been associated with severe CRS and ICANS, as has C-reactive protein (CRP), while increased creatinine is seen only in a minority of advanced severe CRS cases. We hypothesized that EASIX and 2 new modified EASIX formulas (simplified EASIX, which excludes creatinine, and modified EASIX [m-EASIX], which replaces creatinine with CRP [mg/dL]), calculated peri-CAR T-cell infusion, would be associated with development of severe (grade ≥ 3) CRS and ICANS. We included 118 adults, 53 with B-acute lymphoblastic leukemia treated with 1928z CAR T cells (NCT01044069) and 65 with diffuse large B-cell lymphoma treated with axicabtagene ciloleucel or tisagenlecleucel. The 3 formulas showed similar predictive power for severe CRS and ICANS. However, low PLTs and high CRP values were the only variables individually correlated with these toxicities. Moreover, only m-EASIX was a significant predictor of disease response. m-EASIX could discriminate patients who subsequently developed severe CRS preceding the onset of severe symptoms (area under the curve [AUC] at lymphodepletion, 80.4%; at day −1, 73.0%; and at day +1, 75.4%). At day +3, it also had high discriminatory ability for severe ICANS (AUC, 73%). We propose m-EASIX as a clinical tool to potentially guide individualized management of patients at higher risk for severe CAR T-cell–related toxicities.
Pregnancy in women with an inferior vena cava filter: a tertiary center experience and overview of the literature
Authors: Bistervels Ingrid M. , Geerlings Abby E. , Bonta Peter I. , Ganzevoort Wessel , Zijlstra IJsbrand A.J. , Middeldorp Saskia
Published: August 2021

Patients with an inferior vena cava (IVC) filter that remains in situ encounter a lifelong increased risk of deep vein thrombosis and IVC filter complications including fracture, perforation, and IVC filter thrombotic occlusion. Data on the safety of becoming pregnant with an in situ IVC filter are scarce. The objective was to evaluate the risk of complications of in situ IVC filters during pregnancy. We performed a retrospective cohort study of pregnant patients with an in situ IVC filter from a tertiary center between 2000 and 2020. We collected data on complications of IVC filters and pregnancy outcomes. Additionally, we performed a systematic literature search in MEDLINE, Embase, and gray literature. We identified 7 pregnancies in 4 patients with in situ IVC filters with a mean time since IVC filter insertion of 3 years (range, 1-8). No complications of IVC filter occurred during pregnancy. Review of literature yielded five studies including 13 pregnancies in 9 patients. In 1 pregnancy a pre-existent, until then asymptomatic, chronic perforation of the vena cava wall by the IVC filter caused major bleeding and uterine trauma with fetal loss. Overall, the complication rate was 5%. It seems safe to become pregnant with an indwelling IVC filter that is intact and does not show signs of perforation, but because of the low number of cases, no firm conclusions about safety of in situ IVC filters during pregnancy can be drawn. We suggest imaging before pregnancy to reveal asymptomatic IVC filter complications.
Factors associated with do-not-resuscitate document completion among patients hospitalized in geriatric ward
Authors: Wu Chien-Yi , Jen Chun-Hao , Chuang Yun-Shiuan , Fang Tzu-Jung , Wu Yu-Hsuan , Wu Ming-Tsang
Published: August 2021

Background

With a rapidly aging population, there is an increasing need for do-not-resuscitate (DNR) and advance care planning (ACP) discussions. This study investigated the factors associated with signing DNR documents of older patients in the geriatric ward.

Methods

We conducted a retrospective cohort study at a geriatric ward in a tertiary hospital in Southern Taiwan. Three hundred and thirty-seven hospitalized older patients aged ≥65 years in the geriatric ward from 2018 to 2019. The Hospital Information System and electronic medical records were accessed to obtain details regarding patients’ demographics, daily living activities, serum albumin level, nutrition screening score, intensive care unit transferal, resuscitation procedure, days of hospital stay, and survival status on discharge, and DNR status was recorded retrospectively. Patients were classified into DNR and non-DNR groups, with t-tests and Chi-square tests applied to compare the differences between groups. Logistic regression was performed to predict factors related to the DNR documents.

Results

A total of 337 patients were included, 66 of whom had signed a DNR during hospitalization. After multivariate logistic regression, age 85 or more compared to age 65–74 (adjusted odds ratio, aOR 5.94), poor nutrition with screening score two or more (aOR 2.71), albumin level less than 3 (aOR 3.24), Charlson Comorbidity Index higher than 2 (aOR 2.46) and once transferred to ICU (aOR 5.11) were independently associated with DNR documentation during hospitalization.

Conclusions

Several factors related to DNR documents for geriatric patients were identified which could provide clinical information for physicians, patients, and their families to discuss DNR and ACP.
Colorectal cancer survival among Ministry of National Guard-Health Affairs (MNG-HA) population 2009–2017: retrospective study
Authors: Alyabsi Mesnad , Sabatin Fouad , Ramadan Majed , Jazieh Abdul Rahman
Published: August 2021

Background

Colorectal cancer (CRC) is the most diagnosed cancer among males and third among females in Saudi Arabia, with up to two-third diagnosed at advanced stage. The objective of our study was to estimate CRC survival and determine prognostic factors.

Methods

Ministry of National Guard- Health Affairs (MNG-HA) registry data was utilized to identify patients diagnosed with CRC between 2009 and 2017. Cases were followed until December 30th, 2017 to assess their one-, three-, and five-year CRC-specific survivals. Kaplan-Meier method and Cox proportional hazard models were used to assess survival from CRC.

Results

A total of 1012 CRC patients were diagnosed during 2009–2017. Nearly, one-fourth of the patients presented with rectal tumor, 42.89% with left colon and 33.41% of the cases were diagnosed at distant metastasis stage. The overall one-, three-, and five-year survival were 83, 65 and 52.0%, respectively. The five-year survival was 79.85% for localized stage, 63.25% for regional stage and 20.31% for distant metastasis. Multivariate analyses showed that age, diagnosis period, stage, nationality, basis of diagnosis, morphology and location of tumor were associated with survival.

Conclusions

Findings reveal poor survival compared to Surveillance, Epidemiology, and End Results (SEER) population. Diagnoses at late stage and no surgical and/or perioperative chemotherapy were associated with increased risk of death. Population-based screening in this population should be considered.
Robust biomarker discovery for hepatocellular carcinoma from high-throughput data by multiple feature selection methods
Authors: Zhang Zishuang , Liu Zhi-Ping
Published: August 2021

Background

Hepatocellular carcinoma (HCC) is one of the most common cancers. The discovery of specific genes severing as biomarkers is of paramount significance for cancer diagnosis and prognosis. The high-throughput omics data generated by the cancer genome atlas (TCGA) consortium provides a valuable resource for the discovery of HCC biomarker genes. Numerous methods have been proposed to select cancer biomarkers. However, these methods have not investigated the robustness of identification with different feature selection techniques.

Methods

We use six different recursive feature elimination methods to select the gene signiatures of HCC from TCGA liver cancer data. The genes shared in the six selected subsets are proposed as robust biomarkers. Akaike information criterion (AIC) is employed to explain the optimization process of feature selection, which provides a statistical interpretation for the feature selection in machine learning methods. And we use several methods to validate the screened biomarkers.

Results

In this paper, we propose a robust method for discovering biomarker genes for HCC from gene expression data. Specifically, we implement recursive feature elimination cross-validation (RFE-CV) methods based on six different classication algorithms. The overlaps in the discovered gene sets via different methods are referred as the identified biomarkers. We give an interpretation of the feature selection process based on machine learning using AIC in statistics. Furthermore, the features selected by the backward logistic stepwise regression via AIC minimum theory are completely contained in the identified biomarkers. Through the classification results, the superiority of interpretable robust biomarker discovery method is verified.

Conclusions

It is found that overlaps among gene subsets contain different quantitative features selected by the RFE-CV of 6 classifiers. The AIC values in the model selection provide a theoretical foundation for the feature selection process of biomarker discovery via machine learning. What’s more, genes containing in more optimally selected subsets make better biological sense and implication. The quality of feature selection is improved by the intersections of biomarkers selected from different classifiers. This is a general method suitable for screening biomarkers of complex diseases from high-throughput data.
Integrative enrichment analysis of gene expression based on an artificial neuron
Authors: Jiang Xue , Pan Weihao , Chen Miao , Wang Weidi , Song Weichen , Lin Guan Ning
Published: August 2021

Background

Huntington’s disease is a kind of chronic progressive neurodegenerative disease with complex pathogenic mechanisms. To data, the pathogenesis of Huntington’s disease is still not fully understood, and there has been no effective treatment. The rapid development of high-throughput sequencing technologies makes it possible to explore the molecular mechanisms at the transcriptome level. Our previous studies on Huntington’s disease have shown that it is difficult to distinguish disease-associated genes from non-disease genes. Meanwhile, recent progress in bio-medicine shows that the molecular origin of chronic complex diseases may not exist in the diseased tissue, and differentially expressed genes between different tissues may be helpful to reveal the molecular origin of chronic diseases. Therefore, developing integrative analysis computational methods for the multi-tissues gene expression data, exploring the relationship between differentially expressed genes in different tissues and the disease, can greatly accelerate the molecular discovery process.

Methods

For analysis of the intra- and inter- tissues’ differentially expressed genes, we designed an integrative enrichment analysis method based on an artificial neuron (IEAAN). Firstly, we calculated the differential expression scores of genes which are seen as features of the corresponding gene, using fold-change approach with intra- and inter- tissues’ gene expression data. Then, we weighted sum all the differential expression scores through a sigmoid function to get differential expression enrichment score. Finally, we ranked the genes according to the enrichment score. Top ranking genes are supposed to be the potential disease-associated genes.

Results

In this study, we conducted large amounts of experiments to analyze the differentially expressed genes of intra- and inter- tissues. Experimental results showed that genes differentially expressed between different tissues are more likely to be Huntington’s disease-associated genes. Five disease-associated genes were selected out in this study, two of which have been reported to be implicated in Huntington’s disease.

Conclusions

We proposed a novel integrative enrichment analysis method based on artificial neuron (IEAAN), which displays better prediction precision of disease-associated genes in comparison with the state-of-the-art statistical-based methods. Our comprehensive evaluation suggests that genes differentially expressed between striatum and liver tissues of health individuals are more likely to be Huntington’s disease-associated genes.
External fixation versus elastic stable intramedullary nailing in the treatment of open tibial shaft fractures in children
Authors: Hong Pan , Rai Saroj , Tang Xin , Liu Ruikang , Li Jin
Published: August 2021

Introduction

External fixator (EF) is a popular choice for open tibial fractures, but pin tract infection (PTI) and refracture are common complications. Elastic stable intramedullary nail (ESIN) has been reported in the treatment for open tibial fractures. This study aims to compare the clinical outcomes of EF vs. ESIN in the treatment for open tibial shaft fracture in children retrospectively.

Methods

Patients aged 5–11 years with Gustilo-Anderson II and IIIA tibial shaft fracture treated at our institute from January 2008 to January 2018 were reviewed retrospectively and categorized into EF and ESIN groups. Patients with pathological fracture, neuromuscular disorder, metabolic disease, previous tibial fracture or instrumentation, and polytrauma were excluded. Patients with follow-up < 24 months or incomplete medical records were also excluded.

Results

In all, 55 patients (33 males, 22 females) were included in the EF group, whereas 37 patients (21 males, 16 females) were included in the ESIN group. There was no statistically significant difference between the two groups concerning sex, age, body weight, duration from injury to surgery, Gustilo-Anderson (GA) classification, and concomitant injuries. There was no case of nonunion and malunion in either group. The angulation at the latest follow-up was higher in the EF group than the ESIN group (P < 0.01). The radiological union was faster in the ESIN group (7.0 ± 0.9 weeks) than those in the EF group (9.0 ± 2.2 weeks) (P < 0.01). Limb length discrepancy (LLD) was more in the EF group (12.1 ± 4.4, mm) than in the ESIN group (7.3 ± 4.3, mm) (P < 0.01).

Conclusion

ESIN is a viable option in selected patients of GA grade II and IIIA open tibial fractures with comparable clinical outcomes as external fixator. Pin tract infection is the most troublesome complication in the EF group while implant prominence is a nuisance in the ESIN group.
Poliovirus receptor (PVR)-like protein cosignaling network: new opportunities for cancer immunotherapy
Authors: Wu Baokang , Zhong Chongli , Lang Qi , Liang Zhiyun , Zhang Yizhou , Zhao Xin , Yu Yang , Zhang Heming , Xu Feng , Tian Yu
Published: August 2021

Immune checkpoint molecules, also known as cosignaling molecules, are pivotal cell-surface molecules that control immune cell responses by either promoting (costimulatory molecules) or inhibiting (coinhibitory molecules) a signal. These molecules have been studied for many years. The application of immune checkpoint drugs in the clinic provides hope for cancer patients. Recently, the poliovirus receptor (PVR)-like protein cosignaling network, which involves several immune checkpoint receptors, i.e., DNAM-1 (DNAX accessory molecule-1, CD226), TIGIT (T-cell immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM)), CD96 (T cell activation, increased late expression (TACLILE)), and CD112R (PVRIG), which interact with their ligands CD155 (PVR/Necl-5), CD112 (PVRL2/nectin-2), CD111 (PVRL1/nectin-1), CD113 (PVRL3/nectin-3), and Nectin4, was discovered. As important components of the immune system, natural killer (NK) and T cells play a vital role in eliminating and killing foreign pathogens and abnormal cells in the body. Recently, increasing evidence has suggested that this novel cosignaling network axis costimulates and coinhibits NK and T cell activation to eliminate cancer cells after engaging with ligands, and this activity may be effectively targeted for cancer immunotherapy. In this article, we review recent advances in research on this novel cosignaling network. We also briefly outline the structure of this cosignaling network, the signaling cascades and mechanisms involved after receptors engage with ligands, and how this novel cosignaling network costimulates and coinhibits NK cell and T cell activation for cancer immunotherapy. Additionally, this review comprehensively summarizes the application of this new network in preclinical trials and clinical trials. This review provides a new immunotherapeutic strategy for cancer treatment.
Data from expressed sequence tags from the organs and embryos of parthenogenetic Haemaphysalis longicornis
Authors: Umemiya-Shirafuji Rika , Zhou Jinlin , Liao Min , Battsetseg Badgar , Boldbaatar Damdinsuren , Hatta Takeshi , Kuboki Thasaneeya , Sakaguchi Takeshi , Chee Huey Shy , Miyoshi Takeharu , Huang Xiaohong , Tsuji Naotoshi , Xuan Xuenan , Fujisaki Kozo
Published: August 2021

Objectives

Haemaphysalis longicornis is the most important tick species in Japan and has a wide range of vector capacity. Due to its veterinary and medical importance, this tick species has been used as a model for tick/vector biological studies. To identify the key molecules associated with physiological processes during blood feeding and embryogenesis, full-length cDNA libraries were constructed using the fat body, hemocytes-containing hemolymph, midgut, ovary and salivary glands of fed females and embryos of the laboratory colony of parthenogenetic H. longicornis. The sequences of cDNA from the salivary glands had been already released. However, the related information is still poor, and the other expressed sequence tags have not yet been deposited.

Data description

A total of 39,113 expressed sequence tags were obtained and deposited at the DNA DataBank of Japan. There were 7745 sequences from embryos, 7385 from the fat body, 8303 from the hemolymph including hemocytes, 7385 from the midgut, and 8295 from the ovary. The data, including expressed sequence tags from the salivary glands was summarized into Microsoft Excel files. Sharing this data resource with the tick research community will be valuable for the identification of novel genes and advance the progress of tick research.