bluuebunny/crossref_metadata_2025 huggingface dataset:
An experimental and analytical investigation of reinforced concrete beam-column joints strengthened with a range of CFRP schemes applied only to the beam
Authors: Ali Sarmad Abdulsahab , Forth John P.
Published: May 2021

This paper investigates the experimental and analytical behaviour of beam-column joints that are subjected to a combination of torque, flexural and direct shear forces, where different Carbon Fibre Polymer (CFRP) strengthening wraps have been applied only to the beam. These wrapping schemes have previously been determined by the research community as an effective method of enhancing the torsional capacities of simply supported reinforced concrete beams. In this investigation, four 3/4-scale exterior beam-column joints were subjected to combined monotonic loading; three different beam wrapping schemes were employed to strengthen the beam region of the joint. The paper suggests a series of rational formulae, based on the space truss mechanism, which can be used to evaluate the joint shear demand of the beams wrapped in these various ways. Further, an iterative model, based on the average stress-strain method, has been introduced to predict joint strength. The proposed analytical approaches show good agreement with the experimental results. The experimental outcomes along with the adopted analytical methods reflect the consistent influence of the wrapping ratio, the interaction between the combined forces, the concrete strut capacity and the fibre orientation on the joint forces, the failure mode and the distortion levels. A large rise in the strut force resulting from shear stresses generated from this combination of forces is demonstrated and leads to a sudden-brittle failure. Likewise, increases in the beams’ main steel rebar strains are identified at the column face, again influenced by the load interactions and the wrapping systems used.
Preliminary Outcomes of Viabahn Balloon-Expandable Endoprosthesis as Bridging Stent in Renal Arteries During Fenestrated Endovascular Aortic Repair
Authors: Mezzetto Luca , Mastrorilli Davide , Leone Nicola , Gennai Stefano , Silingardi Roberto , Veraldi Gian Franco , Piazza Michele , Squizzato Francesco , Antonello Michele
Published: May 2021

Purpose:

To report preliminary outcomes of Viabahn Balloon-Expandable Endoprosthesis (VBX) stent-graft as bridging stent for renal arteries in fenestrated endovascular aneurysm repair (FEVAR).

Materials and Methods:

Between 2018 and 2019, patients undergoing FEVAR at 3 referral Italian university hospitals were prospectively collected. During the study period, VBX was the first-line choice as bridging stent for renal arteries. Procedural and anatomical data were analyzed, including renal artery (RA) configuration. A dedicated software (3Mensio, Vascular Imaging, Bilthoeven, The Netherlands) was used and RA anatomy classified as follow: upward-oriented in case of any angle >30° above the horizontal or transverse axis perpendicular to the aortic axis, downward-oriented if there was an angle >30° measured below the transverse axis and downward + upward in case of an angle <30° associated with a renal artery angulation >90°. Primary endpoints were technical success, defined as complete deployment of the fenestrated endograft without target vessel (TV) loss, limb stenosis or occlusion and type I or III endoleak, and freedom from target artery instability (TAI), defined by target vessel-related death, occlusion, rupture or reintervention for stenosis, endoleak or disconnection. Secondary endpoints were target artery patency rate and freedom from reinterventions.

Results:

A total of 26 elective FEVAR for juxta/pararenal aneurysm (20), thoracoabdominal type II (3) and type IV (3) were included. Fifty-one RA were planned for revascularization. Of these, 32 were downward, 10 horizontal, 6 upward, 4 were downward + upward. Technical success was achieved in 88.5% (23/26) of patients and 94.2% (48/51) of the TVs. One occlusion (2.1%) occurred within 30 days in a patient with previous endovascular aortic repair and suprarenal fixation. During follow-up (median 10 months), there was 1 type IC endoleak after 6 months (2.1%) in a patient with upward plus downward arterial orientation. Freedom from TAI was 96.1% (CI = 0.89 to 1.04) at first month and 92.3% (CI = 0.82 to 1.03) at 6 months. No aneurysm-related mortality and renal insufficiency occurred during follow-up.

Conclusion:

The use of VBX as bridging stent of RA in FEVAR is safe and feasible. Previous EVAR and tortuosity of RA may be a challenging on target vessel fate.
Knockdown of CENPW Inhibits Hepatocellular Carcinoma Progression by Inactivating E2F Signaling
Authors: Zhou Yajing , Chai Hua , Guo Lei , Dai Zhongqiu , Lai Jianming , Duan Jianping , Liu Yanting , Ding Qian
Published: May 2021

Aim:

This study aimed to evaluate the effects of centromere protein W (CENPW, also known as CUG2) in hepatocellular carcinoma (HCC).

Methods:

CENPW expression in HCC tissues and cells was detected by RT-qPCR assay. CCK-8 and colony formation assay were used to assess cell proliferation. Wound healing and Transwell assay was used to detect cell migration and invasion, respectively. The flow cytometry was used to analyze the cell cycle distribution and apoptosis.

Results:

CENPW expression was upregulated in HCC tissues and cells. Knockdown of CENPW inhibited cell proliferation, migration, and invasion and induced the G0/G1 phase arrest and cell apoptosis in HCC cells, which might involve the E2F signaling regulation.

Conclusion:

CENPW acted as an oncogenic role in HCC progression via activation E2F signaling. Our findings may provide new insights into the studying mechanisms of HCC.
Photobiomodulation as an Adjunct Therapy in Wound Healing
Authors: Nair Harikrishna K. R. , Chong Sylvia S. Y. , Selvaraj Daryl D. J.
Published: May 2021

“Light amplification by stimulated emission of radiation” or more commonly known as Laser has become very popular in the field of dermatology and aesthetic medicine over the past decades. For the treatment of wound healing, a combination of different wavelengths for laser therapy has been introduced which includes 660, 800, and 970 nm. The aim of this study was to note wound healing utilizing photobiomodulation as an adjunct therapy by measuring the wound size in terms of length and width (area measurement). Study participants were selected randomly from a pool of patients who were attending for their routine follow-up visits in the Wound Care Unit in Hospital Kuala Lumpur. Eleven patients with chronic wounds of different etiologies, ie, diabetic foot ulcer and nonhealing ulcer, were recruited for this study . Wound assessment was done prior to cleansing using distilled water and followed by debridement if necessary. Subsequently, the laser technician and patients used protective goggles before applying a super intense continuous flow of laser with 3 wavelengths, ie, 660, 800, and 970 nm with 30 kJ of energy with the handpiece over a 3 min period whereby it is focused on the wound milieu and then rotated around the periwound area. There were 9 diabetic foot ulcers and 2 nonhealing ulcers treated with photobiomodulation as an adjunct therapy. All wounds were managed with the standard of care. Three wounds ie, 3 diabetic foot ulcers and 1 nonhealing ulcer were closed completely. Meanwhile, the other 7 ulcers are at 68.2% to 99% in terms of wound area reduction and new granulomatous tissue was present indicating high healing potential. Therefore, the photobiomodulation was effective as an adjunct in the management of diabetic foot and nonhealing ulcers in this case series. A larger sample size would be able to show the significance of this finding.
Like Mother, Like Child. Keeping Control of Seizures During Pregnancy
Authors: Bermeo-Ovalle Adriana
Published: May 2021

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Cooling system based on double-ball motor control valve
Authors: Mu Hongyu , Wang Yinyan , Teng Hong , Jin Yan , Zhao Xingtian , Zhang Xiaolong
Published: May 2021

To realize eco-models based on (where 3R represents reducing, reusing, and recycling), both researchers and automobile development departments use controllable components to reduce vehicle fuel consumption and emissions. In this context, this paper presents the design of a double-ball motor control valve (DB-MCV). When compared with use of a traditional thermostat, use of the proposed valve in a Worldwide Harmonized Light Vehicles Test Cycle (WLTC) allows the coolant temperature to be controlled accurately as per the vehicle operating conditions, with control accuracy of ±1°C. Using this approach, the engine pre-heating time is reduced by 61 s, the total hydrocarbon (THC)) emission is reduced by 6.79%, the CO emission is reduced by 7.18%, and NOX emission is reduced by 4.84%. Under the same vehicle and working conditions, the engine fuel consumption is reduced by 2.31% on average. Under the cabin heating condition, the cabin temperature can be increased by 4.3°C, which improves the thermal comfort of the driver. When the vehicle is stopped after running at high speed and the engine is idling, the coolant temperature in the engine decreases rapidly, which reduces the risk of a hot dip occurring in the engine.
Synthesis and biological activities study of novel phthalimides and phenylpyrazolo[1,5-a]pyrimidines
Authors: Tang Long , Jiang Jianchun , Song Guoqiang , Wang Yajing , Wei Min , Cao Yijing , Huang Xianfeng , Feng Xiaoqing
Published: May 2021

Phosphodiesterase II (PDE2) is mainly distributed in brain and heart cells, and it is a potential therapeutic target for the treatment of central nervous system (CNS) diseases such as Alzheimer’s disease. Based on the structure of the existing PDE2 inhibitor BAY60-7550, a series of novel phthalimides and phenylpyrazolo[1,5- a]pyrimidines have been designed and prepared. Furthermore, after evaluating their inhibitory activity toward PDE2, compound 7-oxo- N-phenethyl-5-phenyl-4,7-dihydropyrazolo[1,5- a]pyrimidine-3-carboxamide is found to have the optimum inhibitory potential (IC50: 1.82 ± 0.29 μM). Discovery Studio software used to simulate the structure–activity relationship between this compound and the PDE2 protein crystal 4HTX to illustrate the binding modes, which provides favorable guidance for the further development of effective PDE2 inhibitors.
Baricitinib in the treatment of rheumatoid arthritis: clinical and ultrasound evaluation of a real-life single-centre experience
Authors: Tesei Giulia , Cometi Laura , Nacci Francesca , Terenzi Riccardo , Tofani Lorenzo , Capassoni Marco , Bartoli Francesca , Fiori Ginevra , Matucci-Cerinic Marco , Bruni Cosimo
Published: May 2021

Background:

Ultrasound (US) is useful in monitoring RA patients, with the US7 score allowing grey-scale and power-Doppler (PD) semi-quantitative evaluation of synovitis and teno-synovitis. We evaluated real-life efficacy and safety of Baricitinib, an oral selective JAK1-2 inhibitor, in RA patients using clinical, clinimetric, and US assessments.

Methods:

Disease activity score in 28 joints calculated with C-reactive protein (DAS28-CRP), disease activity score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), simplified disease activity index (SDAI), visual analogue scale (VAS)-pain, health assessment questionnaire (HAQ), COCHIN scale, adverse events (AE), concomitant medications, laboratory parameters, and US7 were performed/recorded at baseline, 1, 3, and 6 months in RA patients starting Baricitinib. Responder/non-responder status was determined according to the EULAR Response Criteria at 3 months. SDAI clinical remission or low disease activity (LDA) were calculated at 3 and 6 months.

Results:

In 43 enrolled patients, a significant improvement in disease activity and US7 components (except tendon PD) and a reduction of steroid dosage were observed. Responders at 3 months showed a significantly higher reduction of CDAI, SDAI, COCHIN scale, VAS-pain, and US7 synovialPD, compared with non-responders. At 3 and 6 months, remission/LDA was achieved by 12.8/53.8% and 21.6/51.3% patients, respectively. The csDMARD co-treatment was independently associated with remission/LDA at 3 months. Safety-related drop-outs were in line with literature data. The steroid dosage was associated with AE development at 6 months.

Conclusion:

The real-life data, also obtained with US evaluation, confirmed the Baricitinib efficacy in RA disease control, as well as the utility of assessment during the follow up of disease activity.
Protective Effects and Mechanism of Hyperoside in PC12 Cells Against Oxidative Stress Injury Induced by Hydrogen Peroxide
Authors: Feng Yan , Wang Dongxu , Wang Qi , Li Zhifeng , Yang Shi-Lin , Feng Yu-Lin , Luo Tao , Li Yan
Published: May 2021

As the aging phenomenon continues to increase, the incidence of neurodegenerative diseases continues to increase annually. As one of the significant contributive factors of neurodegenerative diseases, oxidative stress damage has received extensive attention in recent years. Oxidative stress plays an important role in neuronal damage through various apoptotic mechanisms related to neurodegenerative diseases. The use of natural antioxidants to combat oxidative stress may be a useful approach in delaying disease progression. In this study, we explored the neuroprotective effect of hyperoside on rat pheochromoma (PC12) cells. Specifically, the antioxidant effect and mechanism of hyperoside in hydrogen peroxide (H2O2)-induced cellular cytotoxicity were investigated. Our results showed that hyperoside could significantly increase the survival rate of rat PC12 cells when exposed to H2O2. In addition, hyperoside regulated the expression of genes and proteins in the corresponding pathways by up-regulating the phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), and light chain 3β (LC3B) pathways and down-regulating the nuclear factor-ᴋ-gene binding (NF-κB), Bcl2-associated X (Bax), cysteinyl aspartate specific proteinase 3 (Caspase 3), and P62 pathways, thereby inhibiting cell apoptosis. Therefore, hyperoside can effectively inhibit H2O2-induced oxidative stress damage by regulating inflammation, autophagy, and apoptosis-related pathways.
Navigating High-Choice European Political Information Environments: a Comparative Analysis of News User Profiles and Political Knowledge
Authors: Castro Laia , Strömbäck Jesper , Esser Frank , Van Aelst Peter , de Vreese Claes , Aalberg Toril , Cardenal Ana S. , Corbu Nicoleta , Hopmann David Nicolas , Koc-Michalska Karolina , Matthes Jörg , Schemer Christian , Sheafer Tamir , Splendore Sergio , Stanyer James , Stępińska Agnieszka , Štětka Václav , Theocharis Yannis
Published: May 2021

The transition from low- to high-choice media environments has had far-reaching implications for citizens’ media use and its relationship with political knowledge. However, there is still a lack of comparative research on how citizens combine the usage of different media and how that is related to political knowledge. To fill this void, we use a unique cross-national survey about the online and offline media use habits of more than 28,000 individuals in 17 European countries. Our aim is to (i) profile different types of news consumers and (ii) understand how each user profile is linked to political knowledge acquisition. Our results show that five user profiles – news minimalists, social media news users, traditionalists, online news seekers, and hyper news consumers – can be identified, although the prevalence of these profiles varies across countries. Findings further show that both traditional and online-based news diets are correlated with higher political knowledge. However, online-based news use is more widespread in Southern Europe, where it is associated with lower levels of political knowledge than in Northern Europe. By focusing on news audiences, this study provides a comprehensive and fine-grained analysis of how contemporary European political information environments perform and contribute to an informed citizenry.
Psychoeducational Program for the Family Member Caregivers of People with Dementia to Reduce Perceived Burden and Increase Patient’s Quality of Life: A Randomized Controlled Trial
Authors: Tawfik Nadia M. , Sabry Noha A. , Darwish Hatem , Mowafy Maha , Soliman Saeed S.A.
Published: May 2021

Background:

Dementia is one of the world’s greatest public health issues. Most people with dementia receive home care, and family members are vulnerable to feeling burdened and depressed that reinforces the need for caregiver-driven services to mitigate these negative effects.

Objective:

The purpose of this research was to evaluate the effect of the psychoeducational program on burden and quality of life of family caregivers for people with dementia.

Methods:

This randomized controlled trial (RCT) was conducted on 60 family caregivers. Participants were randomly assigned to receive either the 8-session psychoeducational program (study group) or routine care only (control group). The demographic data of the caregivers and their patients, the burden of caregivers using Zarit Burden Interview (ZBI), and the quality of life of the patients using Quality of Life in Alzheimer Disease (QoL-AD) questionnaire were measured before and after the psychoeducational program and compared between the study group and the control group.

Results:

The results revealed that 80% of the family caregivers were female and 42% were daughters. The mean ± SD of the baseline burden was 61 ± 13.7 and 60.9 ± 10 in the study and the control group, respectively. ZBI burden score in the study group demonstrated a significant drop after the psychoeducational program compared to the control group. Logistic regression analysis showed that caregivers who received the psychoeducational program have OR (95% CI) of 14 (3.1-67.8) compared to those who did not receive the psychoeducational program.

Conclusions:

Psychoeducational program is effective in reducing the family caregivers’ perceived burden. These findings need to be considered in developing comprehensive dementia care programs to well increase the strategies that help caregivers to deal with their patients.
Translating Data Analytics Into Improved Spine Surgery Outcomes: A Roadmap for Biomedical Informatics Research in 2021
Authors: Greenberg Jacob K. , Otun Ayodamola , Ghogawala Zoher , Yen Po-Yin , Molina Camilo A. , Limbrick David D. , Foraker Randi E , Kelly Michael P. , Ray Wilson Z.
Published: May 2021

Study Design:

Narrative review.

Objectives:

There is growing interest in the use of biomedical informatics and data analytics tools in spine surgery. Yet despite the rapid growth in research on these topics, few analytic tools have been implemented in routine spine practice. The purpose of this review is to provide a health information technology (HIT) roadmap to help translate data assets and analytics tools into measurable advances in spine surgical care.

Methods:

We conducted a narrative review of PubMed and Google Scholar to identify publications discussing data assets, analytical approaches, and implementation strategies relevant to spine surgery practice.

Results:

A variety of data assets are available for spine research, ranging from commonly used datasets, such as administrative billing data, to emerging resources, such as mobile health and biobanks. Both regression and machine learning techniques are valuable for analyzing these assets, and researchers should recognize the particular strengths and weaknesses of each approach. Few studies have focused on the implementation of HIT, and a variety of methods exist to help translate analytic tools into clinically useful interventions. Finally, a number of HIT-related challenges must be recognized and addressed, including stakeholder acceptance, regulatory oversight, and ethical considerations.

Conclusions:

Biomedical informatics has the potential to support the development of new HIT that can improve spine surgery quality and outcomes. By understanding the development life-cycle that includes identifying an appropriate data asset, selecting an analytic approach, and leveraging an effective implementation strategy, spine researchers can translate this potential into measurable advances in patient care.
Odontoid Fracture as Proximal Junctional Failure in Patients With Multilevel Spine Fusions
Authors: Ladd Bryan M. , Martin Christopher T. , Sembrano Jonathan N. , Jones Kristen E. , Polly David W. , Hunt Matthew A.
Published: May 2021

Study Design:

Retrospective study.

Objective:

Proximal junctional failure (PJF) commonly occurs as a recognized potential outcome of fusion surgery. Here we describe a unique series of patients with multilevel spine fusion including the cervical spine, who developed PJF as an odontoid fracture.

Methods:

We performed a single site retrospective review of patients with prior fusion that included a cervical component, who presented with an odontoid fracture between 2012 and 2019. Radiographic measurements included C2-C7 SVA, C2-C7 lordosis, T1 slope, Occiput-C2 angle, proximal junctional kyphosis, and cervical mismatch. Associated fractures, medical comorbidities, and treatments were determined via chart review after IRB approval.

Results:

Nine patients met inclusion criteria. 5 reported trauma with subsequent onset of pain. All patients sustained a Type II odontoid fracture. 5 with associated C1/Jefferson fractures. In all patients, pre-injury Occiput-C2 angle was outside normative range; C2-C7 SVA was greater than 4 cm in 6 patients; T1-slope minus cervical lordosis was greater than 18.5 degrees in 6 patients. 7 patients were treated operatively with extension of fusion to C1 and 2 patients declined operative treatment.

Conclusion:

In this series of 9 patients with multilevel fusion with type II odontoid fractures, all patients demonstrated abnormal pre-fracture sagittal alignment parameters and a greater than normal association of C1 fractures was noted. Further study is needed to establish the role of poor sagittal alignment with compensatory occiput-C2 angulation as a predisposing factor for odontoid fracture as a proximal junctional failure mechanism.
Using the Lower Limb Adduction Angle to Predict Postoperative Knee Joint-Line Obliquity After Open-Wedge High Tibial Osteotomy
Authors: Park Jun-Gu , Bin Seong-Il , Kim Jong-Min , Lee Bum-Sik
Published: May 2021

Background:

Knee joint-line orientation is altered after open-wedge high tibial osteotomy (OWHTO), and excessive joint-line obliquity (JLO) can adversely affect outcomes. Little is known regarding preoperative prediction of postoperative knee JLO.

Purpose/Hypothesis:

The purpose of this study was to assess the correlation between the amount of lower limb adduction and changes in knee JLO after OWHTO. The hypothesis was that postoperative knee JLO could be predicted using the amount of lower limb adduction after OWHTO.

Study Design:

Case series; Level of evidence, 4.

Methods:

The records of 67 patients (77 knees) who underwent OWHTO for medial compartment osteoarthritis were retrospectively reviewed. The mechanical hip-knee-ankle (HKA) axis, lateral distal femoral angle, medial proximal tibial angle (MPTA), knee JLO, ankle JLO, and joint-line convergence angle were measured on standing whole-leg plain radiographs preoperatively and at 1 year postoperatively. The limb adduction angle was defined as the angle between the native weightbearing line (WBL) and the planned WBL on preoperative standing whole-leg plain radiographs. The predicted knee JLO was calculated as the sum of the preoperative knee JLO and the limb adduction angle. Multivariable linear regression analysis was used to identify the preoperative radiologic factors associated with the postoperative knee JLO. The agreement between postoperative and predicted values was determined using intraclass correlation coefficients (ICCs).

Results:

The estimated limb adduction angle was 4.2° ± 1.3°, and the predicted knee JLO was 4.9° ± 3.0°. The actual postoperative knee JLO was 4.5° ± 2.4°, which was a significant increase from 0.7° ± 2.4° preoperatively ( P < .001). Excellent agreement was found between the predicted knee JLO and postoperative knee JLO (ICC = 0.928; P < .001). Limb adduction angle and changes in preoperative MPTA were significantly associated with changes in knee JLO ( P < .001). On multivariable linear regression analysis, preoperative knee JLO and limb adduction angle were significantly associated with postoperative knee JLO ( P < .001; R 2 = 0.83).

Conclusion:

Changes in knee JLO after OWHTO were associated with adduction of the lower limb after OWHTO. During preoperative planning, postoperative knee JLO can be predicted as the sum of the preoperative knee JLO and the limb adduction angle between the preoperative WBL and planned WBL.
European Stroke Organisation (ESO) guidelines on blood pressure management in acute ischaemic stroke and intracerebral haemorrhage
Authors: Sandset Else Charlotte , Anderson Craig S , Bath Philip M , Christensen Hanne , Fischer Urs , Gąsecki Dariusz , Lal Avtar , Manning Lisa S , Sacco Simona , Steiner Thorsten , Tsivgoulis Georgios
Published: May 2021

The optimal blood pressure (BP) management in acute ischaemic stroke (AIS) and acute intracerebral haemorrhage (ICH) remains controversial. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist physicians in their clinical decisions regarding BP management in acute stroke.

The guidelines were developed according to the ESO standard operating procedure and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations based on the GRADE approach. Despite several large randomised-controlled clinical trials, quality of evidence is generally low due to inconsistent results of the effect of blood pressure lowering in AIS. We recommend early and modest blood pressure control (avoiding blood pressure levels >180/105 mm Hg) in AIS patients undergoing reperfusion therapies. There is more high-quality randomised evidence for BP lowering in acute ICH, where intensive blood pressure lowering is recommended rapidly after hospital presentation with the intent to improve recovery by reducing haematoma expansion. These guidelines provide further recommendations on blood pressure thresholds and for specific patient subgroups.

There is ongoing uncertainty regarding the most appropriate blood pressure management in AIS and ICH. Future randomised-controlled clinical trials are needed to inform decision making on thresholds, timing and strategy of blood pressure lowering in different acute stroke patient subgroups.
Therapeutic administration of etoposide coincides with reduced systemic HMGB1 levels in macrophage activation syndrome
Authors: Palmblad Karin , Schierbeck Hanna , Sundberg Erik , Horne Anna-Carin , Erlandsson Harris Helena , Henter Jan-Inge , Andersson Ulf
Published: May 2021

Background

Macrophage activation syndrome (MAS) is a potentially fatal complication of systemic inflammation. HMGB1 is a nuclear protein released extracellularly during proinflammatory lytic cell death or secreted by activated macrophages, NK cells, and additional cell types during infection or sterile injury. Extracellular HMGB1 orchestrates central events in inflammation as a prototype alarmin. TLR4 and the receptor for advanced glycation end products operate as key HMGB1 receptors to mediate inflammation.

Methods

Standard ELISA and cytometric bead array-based methods were used to examine the kinetic pattern for systemic release of HMGB1, ferritin, IL-18, IFN-γ, and MCP-1 before and during treatment of four children with critical MAS. Three of the patients with severe underlying systemic rheumatic diseases were treated with biologics including tocilizumab or anakinra when MAS developed. All patients required intensive care therapy due to life-threatening illness. Add-on etoposide therapy was administered due to insufficient clinical response with standard treatment. Etoposide promotes apoptotic rather than proinflammatory lytic cell death, conceivably ameliorating subsequent systemic inflammation.

Results

This therapeutic intervention brought disease control coinciding with a decline of the increased systemic HMGB1, IFN-γ, IL-18, and ferritin levels whereas MCP-1 levels evolved independently.

Conclusion

Systemic HMGB1 levels in MAS have not been reported before. Our results suggest that the molecule is not merely a biomarker of inflammation, but most likely also contributes to the pathogenesis of MAS. These observations encourage further studies of HMGB1 antagonists. They also advocate therapeutic etoposide administration in severe MAS and provide a possible biological explanation for its mode of action.
Predictive value of standard serum markers for bone metastases in prostate cancer
Authors: Ozdemir Semra , Ersay Ahmet Reşit , Koc Ozturk Fulya , Ozdemir Beril Su
Published: May 2021

Background

The early detection of bone metastases is very important in prostate cancer follow-up. This study aimed to compare conventional tumor markers, namely free prostate-specific antigen (free PSA), total prostate-specific antigen (total PSA), free PSA/total PSA ratio, alkaline phosphatase (ALP) values, Gleason scores and 99 m Tc-MDP bone scintigraphy findings in the prediction of bone metastases in prostate cancer.

Methods

In total, 175 patients with prostate cancer who underwent whole-body bone scintigraphy were included in the study. All selected scintigraphic studies were reprocessed. Free PSA, total PSA, free PSA/total PSA ratio, alkaline phosphatase (ALP) values and Gleason scores of patients were recorded.

Results

The results of our study show that the presence of bone metastasis correlates very weakly with free PSA/total PSA ratio (rho = 0.179), weakly with total PSA (rho = 0.318) and Gleason score (rho = 0.382), moderately with ALP (rho = 0.539), free PSA (0.416). Only ALP variable had a diagnostic value and ALP cutoff value was 76.50 IU/L, with 80% sensitivity and 82.1% specificity.

Conclusion

According to the results of our study; the free PSA, total PSA, free PSA/total PSA ratio and Gleason score values were not considered as a reliable parameter in the prostate cancer cases follow-up for bone metastasis development. Only ALP had a diagnostic value and ALP cutoff value was 76.50 IU / L with 80% sensitivity and 82.1% specificity in predicting bone metastases in prostate cancer.
Methylene blue associated with maghemite nanoparticles has antitumor activity in breast and ovarian carcinoma cell lines
Authors: Silva Ana Luísa G. , Carvalho Natália V. , Paterno Leonardo G. , Moura Ludmilla D. , Filomeno Cleber L. , de Paula Eneida , Báo Sônia N.
Published: May 2021

Background

Cancer constitutes group of diseases responsible for the second largest cause of global death, and it is currently considered one of the main public health concerns nowadays. Early diagnosis associated with the best choice of therapeutic strategy, is essential to achieve success in cancer treatment. In women, breast cancer is the second most common type, whereas ovarian cancer has the highest lethality when compared to other neoplasms of the female genital system. The present work, therefore, proposes the association of methylene blue with citrate-coated maghemite nanoparticles (MAGCIT–MB) as a nanocomplex for the treatment of breast and ovarian cancer.

Results

In vitro studies showed that T-47D and A2780 cancer cell lines underwent a significant reduction in cell viability after treatment with MAGCIT–MB, an event not observed in non-tumor (HNTMC and HUVEC) cells and MDA-MB-231, a triple-negative breast cancer cell line. Flow cytometry experiments suggest that the main mechanism of endocytosis involved in the interiorization of MAGCIT–MB is the clathrin pathway, whereas both late apoptosis and necrosis are the main types of cell death caused by the nanocomplex. Scanning electron microscopy and light microscopy reveal significant changes in the cell morphology. Quantification of reactive oxygen species confirmed the MAGCIT–MB cytotoxic mechanism and its importance for the treatment of tumor cells. The lower cytotoxicity of individual solution of maghemite nanoparticles with citrate (MAGCIT) and free methylene blue (MB) shows that their association in the nanocomplex is responsible for its enhanced therapeutic potential in the treatment of breast and ovarian cancer in vitro.

Conclusions

Treatment with MAGCIT–MB induces the death of cancer cells but not normal cells. These results highlight the importance of the maghemite core for drug delivery and for increasing methylene blue activity, aiming at the treatment of breast and ovarian cancer.

Graphic Abstract
tRNA-derived fragments as novel potential biomarkers for relapsed/refractory multiple myeloma
Authors: Xu Cong , Liang Ting , Zhang Fangrong , Liu Jing , Fu Yunfeng
Published: May 2021

Background

tRNA-derived fragments have been reported to be key regulatory factors in human tumors. However, their roles in the progression of multiple myeloma remain unknown.

Results

This study employed RNA-sequencing to explore the expression profiles of tRFs/tiRNAs in new diagnosed MM and relapsed/refractory MM samples. The expression of selected tRFs/tiRNAs were further validated in clinical specimens and myeloma cell lines by qPCR. Bioinformatic analysis was performed to predict their roles in multiple myeloma progression.We identified 10 upregulated tRFs/tiRNAs and 16 downregulated tRFs/tiRNAs. GO enrichment and KEGG pathway analysis were performed to analyse the functions of 1 significantly up-regulated and 1 significantly down-regulated tRNA-derived fragments. tRFs/tiRNAs may be involved in MM progression and drug-resistance.

Conclusion

tRFs/tiRNAs were dysregulated and could be potential biomarkers for relapsed/refractory MM.
Perioperative adherence to continuous positive airway pressure and its effect on postoperative nocturnal hypoxemia in obstructive sleep apnea patients: a prospective cohort study
Authors: Suen Colin , Wong Jean , Warsame Kahiye , Subramani Yamini , Panzarella Tony , Waseem Rida , Auckley Dennis , Chaudhry Rabail , Islam Sazzadul , Chung Frances
Published: May 2021

Background

Although continuous positive airway pressure (CPAP) is the first line treatment for obstructive sleep apnea (OSA) patients, the perioperative adherence rate is unclear. The objective of this study was to determine the perioperative adherence rate of patients with OSA with a CPAP prescription and the effect of adherence on nocturnal oxygen saturation.

Methods

This prospective cohort study included adult surgical patients with a diagnosis of OSA with CPAP prescription undergoing elective non-cardiac surgery. Patients were divided into CPAP adherent and non-adherent groups based on duration of usage (≥ 4 h/night). Overnight oximetry was performed preoperatively and on postoperative night 1 and 2 (N1, N2). The primary outcome was adherence rate and the secondary outcome was nocturnal oxygen saturation.

Results

One hundred and thirty-two patients completed the study. CPAP adherence was 61% preoperatively, 58% on postoperative N1, and 59% on N2. Forty-nine percent were consistently CPAP adherent pre- and postoperatively. Using a linear fixed effects regression, oxygen desaturation index (ODI) was significantly improved by CPAP adherence (p = 0.0011). The interaction term CPAP x N1 was significant (p = 0.0015), suggesting that the effect of CPAP adherence varied on N1 vs preoperatively. There was no benefit of CPAP adherence on postoperative mean SpO2, minimum SpO2, and percentage of sleep duration with SpO2 < 90%. Use of supplemental oxygen therapy was much lower in the CPAP adherent group vs non-adherent group (9.8% vs 46.5%, p <  0.001).

Conclusions

Among patients with a preoperative CPAP prescription, approximately 50% were consistently adherent. CPAP adherence was associated with improved preoperative ODI and the benefit was maintained on N1. These modest effects may be underestimated by a higher severity of OSA in the CPAP adherent group and a higher rate of oxygen supplementation in the non-adherent group.

Trial registration

ClinicalTrials.Gov registry (NCT02796846).
Sex disparities in vitamin D status and the impact on systemic inflammation and survival in rectal cancer
Authors: Abrahamsson Hanna , Meltzer Sebastian , Hagen Vidar Nyløkken , Johansen Christin , Bousquet Paula A. , Redalen Kathrine Røe , Ree Anne Hansen
Published: May 2021

Background

We reported previously that rectal cancer patients given curative-intent chemotherapy, radiation, and surgery for non-metastatic disease had enhanced risk of metastatic progression and death if circulating levels of 25-hydroxyvitamin D [25(OH) D] were low. Here we investigated whether the association between the vitamin D status and prognosis pertains to the general, unselected population of rectal cancer patients.

Methods

Serum 25(OH) D at the time of diagnosis was assessed in 129 patients, enrolled 2013–2017 and representing the entire range of rectal cancer stages, and analyzed with respect to season, sex, systemic inflammation, and survival.

Results

In the population-based cohort residing at latitude 60°N, 25(OH) D varied according to season in men only, who were overrepresented among the vitamin D-deficient (< 50 nmol/L) patients. Consistent with our previous findings, the individuals presenting with T4 disease had significantly reduced 25(OH) D levels. Low vitamin D was associated with systemic inflammation, albeit with distinct modes of presentation. While men with low vitamin D showed circulating markers typical for the systemic inflammatory response (e.g., elevated erythrocyte sedimentation rate), the corresponding female patients had elevated serum levels of interleukin-6 and the chemokine (C-X-C motif) ligand 7. Despite disparities in vitamin D status and the potential effects on disease attributes, significantly shortened cancer-specific survival was observed in vitamin D-deficient patients irrespective of sex.

Conclusion

This unselected rectal cancer cohort confirmed the interconnection of low vitamin D, more advanced disease presentation, and poor survival, and further suggested it may be conditional on disparate modes of adverse systemic inflammation in men and women.

Trial registration

ClinicalTrials.govNCT01816607; registration date: 22 March 2013.
The clinical features and prognosis of patients with mucinous breast carcinoma compared with those with infiltrating ductal carcinoma: a population-based study
Authors: Zhou Xingtong , Zheng Zhibo , Li Yan , Zhao Weiwei , Lin Yan , Zhang Jieshi , Sun Qiang
Published: May 2021

Background

At present, the characteristics of mucinous breast carcinoma (MBC) and the factors affecting its prognosis are controversial. We compared the clinical features of MBC with those of infiltrating ductal carcinoma (IDC) and summarized the relevant prognostic factors.

Methods

The Surveillance, Epidemiology, and End Results (SEER) database includes information on 10,593 patients diagnosed with MBC between 2004 and 2016. Chi-square tests and analyses were used to analyze differences in variables between the MBC and IDC groups. Univariate and multivariate Cox proportional hazards models were used to assess the relative impacts of risk factors on cancer-specific survival (CSS) in patients. Kaplan-Meier survival curves were constructed to assess cancer-specific mortality and were compared using the log-rank test.

Results

From 2004 to 2016, 10,593 people were diagnosed with MBC, and 402,797 were diagnosed with IDC. Patients with MBC had significantly higher 5−/10-year CSS rates (96.4%/93.4%) than those with IDC (89%/83.8%). Compared with IDC patients, MBC patients had less lymph node metastasis, an earlier stage, a higher rate of hormone receptor positivity and a lower expression rate of HER2. Univariate and multivariate analyses showed that age ≥ 60 years old (HR = 1.574, 95%CI: 1.238–2.001, P < 0.001), singled status (HR = 1.676, 95%CI: 1.330–2.112, P < 0.001) and advanced TNM/SEER stage were independent prognostic risk factors for MBC. In addition, positive estrogen receptor (HR = 0.577, 95%CI: 0.334–0.997, P = 0.049), positive progesterone receptor (HR = 0.740, 95%CI: 0.552–0.992, P = 0.044), surgical treatment (HR = 0.395, 95%CI: 0.288–0.542, P < 0.001) and radiotherapy (HR = 0.589, 95%CI: 0.459–0.756, P < 0.001) were identified as protective factors.

Conclusion

Compared with IDC, MBC has a better prognosis. For patients with MBC, we identified prognostic factors that can help clinicians better assess patient outcomes and guide individualized treatment.
Magnetic resonance imaging-guided stereotactic body radiotherapy for prostate cancer (mirage): a phase iii randomized trial
Authors: Ma Ting Martin , Lamb James M. , Casado Maria , Wang Xiaoyan , Basehart T. Vincent , Yang Yingli , Low Daniel , Sheng Ke , Agazaryan Nzhde , Nickols Nicholas G. , Cao Minsong , Steinberg Michael L. , Kishan Amar U.
Published: May 2021

Background

Stereotactic body radiotherapy (SBRT) is becoming increasingly used in treating localized prostate cancer (PCa), with evidence showing similar toxicity and efficacy profiles when compared with longer courses of definitive radiation. Magnetic resonance imaging (MRI)-guided radiotherapy has multiple potential advantages over standard computed tomography (CT)-guided radiotherapy, including enhanced prostate visualization (abrogating the need for fiducials and MRI fusion), enhanced identification of the urethra, the ability to track the prostate in real-time, and the capacity to perform online adaptive planning. However, it is unknown whether these potential advantages translate into improved outcomes. This phase III randomized superiority trial is designed to prospectively evaluate whether toxicity is lower after MRI-guided versus CT-guided SBRT.

Methods

Three hundred men with localized PCa will be randomized in a 1:1 ratio to SBRT using CT or MRI guidance. Randomization will be stratified by baseline International Prostate Symptom Score (IPSS) (≤15 or > 15) and prostate gland volume (≤50 cc or > 50 cc). Five fractions of 8 Gy will be delivered to the prostate over the course of fourteen days, with or without hormonal therapy and elective nodal radiotherapy (to a dose of 5 Gy per fraction) as per the investigator’s discretion. The primary endpoint is the incidence of physician-reported acute grade ≥ 2 genitourinary (GU) toxicity (during the first 90 days after SBRT), as assessed by the CTCAE version 4.03 scale. Secondary clinical endpoints include incidence of acute grade ≥ 2 gastrointestinal (GI) toxicity, 5-year cumulative incidences of physician-reported late grade ≥ 2 GU and GI toxicity, temporal changes in patient-reported quality of life (QOL) outcomes, 5-year biochemical recurrence-free survival and the proportion of fractions of MRI-guided SBRT in which online adaptive radiotherapy is used.

Discussion

The MIRAGE trial is the first randomized trial comparing MRI-guided with standard CT-guided SBRT for localized PCa. The primary hypothesis is that MRI-guided SBRT will lead to an improvement in the cumulative incidence of acute grade ≥ 2 GU toxicity when compared to CT-guided SBRT. The pragmatic superiority design focused on an acute toxicity endpoint will allow an early comparison of the two technologies.

Trial registration

Clinicaltrials.gov identifier: NCT04384770. Date of registration: May 12, 2020.

https://clinicaltrials.gov/ct2/show/NCT04384770

Protocol version

Version 2.1, Aug 28, 2020.
Children’s experiences of participating in a school-based health promotion parental support programme – a qualitative study
Authors: Malek Mahnoush Etminan , Nyberg Gisela , Elinder Liselotte Schäfer , Patterson Emma , Norman Åsa
Published: May 2021

Background

Children’s voices are seldom heard in process evaluations concerning health promotion programmes. A Healthy School Start Plus (HSSP) is a parental support programme, conducted in Sweden, with the aim of promoting healthy diet, physical activity and preventing obesity in preschool class children. The 6-month programme includes: (1) Health information to parents; (2) Motivational Interviewing with parents by school nurses; (3) Classroom activities and home assignments for children; (4) A self-test of type-2 diabetes risk for parents. We aimed to describe children’s experiences of the third component regarding barriers and facilitators of participating in and learning from the classroom activities in the HSSP.

Methods

In total 36 children from 7 schools in Sweden, mean age 6 years, participated in 7 focus group discussions. Purposeful sampling with maximum variation was used to collect the data. The focus groups were audio-recorded, transcribed and analysed using qualitative content analysis.

Results

Four categories were identified; (1) Time available to work on intervention activities; (2) Others’ interest; (3) Abilities and interests in intervention activities; and (4) Practicing the concept of health.

Conclusions

The findings may improve the HSSP and other similar interventions that include classroom-based learning regarding health by highlighting the following points to consider: aiming for homework to be an integrated part of the school-setting to enhance parental involvement; using flexible material, tailored to the children’s abilities and giving children adequate time to finish the intervention activities; and making teachers and parents aware of the importance of verbal and body language regarding intervention activities.

Trial registration

The Healthy School Start Plus trial was retrospectively registered in the International Standard Randomised Controlled Trial Number Registry on January 4, 2018 and available online at ClinicalTrials.gov: No. NCT03390725.
Narcissistic traits in young people and how experiencing shame relates to current attachment challenges
Authors: van Schie Charlotte C. , Jarman Heidi L. , Reis Samantha , Grenyer Brin F. S.
Published: May 2021

Background

Young people with pathological narcissistic traits may have more maladaptive ways of relating to themselves and others. In this study, we investigated how the experience of shame may be a mechanism by which vulnerable and grandiose pathological narcissism relates to negative and positive internalised models of the self and others, manifested as attachment styles.

Methods

Participants (N = 348) were young people who reported on pathological narcissism, the experience of shame and their model of self and others (secure, dismissive, preoccupied and fearful attachment). Mediation of the experience of shame between vulnerable and grandiose narcissism on the one hand and secure, dismissive, preoccupied and fearful attachment on the other hand, was tested using a path model.

Results

Shame mediated the relationship between vulnerable narcissism and a more negative model of others and self (i.e. less secure, more fearful and more preoccupied in attachment). Higher grandiose narcissism traits were related to a more positive model of others and self (i.e. more secure attachment) and were unrelated to the experience of shame.

Conclusions

Young people with vulnerable narcissism traits tended to report more shame, and struggled to be close to others. It may be that shame experiences highlight a discrepancy between the ideal and actual self that may contribute to a more insecure attachment style. A good working alliance and fostering self-compassion may counter some negative effects of shame in those most vulnerable, but dismissal in those most grandiose presents a clinical conundrum requiring further research.