bluuebunny/crossref_metadata_2025 huggingface dataset:
Long Term Haematological Recovery of Children with Severe Malaria Anaemia in Uganda
Authors: Namazzi Ruth , Conroy Andrea L , Datta Dibyadyuti , John Chandy C. , Opoka Robert
Published: November 2019

Long Term Haematological Recovery of Children with Severe Malaria Anaemia in Uganda

Ruth Namazzi, Andrea Conroy, Dibyadyuti Datta, Gloria Kyarisiima Chandy John, Robert Opoka

Background Children with severe malaria anaemia are at an increased risk of poor post discharge outcomes including frequent readmissions and clinic visits for malaria. How the post-discharge outcomes affect haematological recovery of children after severe malaria anaemia has not been evaluated.

Methods We enrolled and followed up for 12 months 248 children with severe malaria anaemia (SMA) and 120 age matched asymptomatic community controls (CC). Complete blood counts, reticulocyte percentages and erythropoietin levels were done at baseline, 1 month and 12 months after the malaria episode. Children were treated according to national guidelines, which included blood transfusion and anti malarial therapy. We evaluated the relationship between recovery of haematological indices and multiple readmissions in the post-discharge period in SMA children.

Results The mean age was 2.12 ± 0.9 and 2.2 ± 1.0 years (p=0.266) for SMA and CC respectively. The mean baseline haemoglobin (Hb), reticulocyte percentage and erythropoietin levels were 3.5 ± 0.9g/dL, 2.6±4.7% and 6843±5891 for SMA, compared to 10.8±1.5g/dL, 1.8±2.6% and 58.5 for CC, respectively. By 1-month, SMA children had made complete haematological recovery with mean Hb, reticulocyte percentage and erythropoietin levels of 11.2 ± 2.2g/dL, 1.8± 2.7% and 20.2 ± 58.3. The hematological recovery was sustained even by month12 follow up; mean Hb level was 10.7±2.1 and 11.6±2.1g/dL for SMA and CC, p =0.07. Reticulocyte percentages were comparable between SMA and CC, 2.5 ± 4.1vs 1.2±1.7,p=0.41. Amongst SMA group, more children who had multiple readmissions during the follow up period were still anemic at 12 months compared to those who did not have multiple readmissions, 7/64(10.9%) vs. 13/168(7.8%). The difference however was not statistically significant (p=0.438).

Conclusion Children with SMA achieve hematological recovery by 1 month post-discharge. The hematological recovery was maintained until 12 months post-discharge. Amongst SMA children, multiple readmissions in the post-discharge period did not appear to adversely affect hematological recovery by 12 months. The effect of repeated malaria episodes on long term haematological recovery needs further study.

Disclosures

Conroy: ALC: Patents & Royalties: angiopoietin-1, angiopoietin-2.
Effect of CXCL14 on Migration of Mds Via CXCL12/CXCR4 Axis in Vitro
Authors: Ying Wang
Published: November 2019

Objective:To detect the expression level of chemokine CXCL-14 in patients with MDS, and to explore how it is regulated and what clinical effects may occour . For the further step ,to find new target in MDS therapy.Method:45 patients with MDS and 28 donors' peripheral blood samples were included. The expression of chemokine CXCL14, CXCL12 / CXCR4 and CXCR7 were detected by ELISA and FCM. Logistic regression analysis confirmed the association between chemokine expression level and disease progression. Kaplan-meier survival analysis ,introducing time factors, show how CXCL14 works on median survival time and cumulative survival. Methylation specific PCR detected the promoter methylation level in CXCL14.To affirm the clinical significaonce of CXCL14 in MDS, the group conduct experiment with cell line SKM-1 and rebuild the cell in the way of CXCL14 and CXCR7 overexpression .CCK-8 cell proliferation experiment tested cell vigor, Flow Cytometry detected cell apoptosis, transwell chemotactic experiment evaluated cell migration and invasion.Result:With the progression of MDS, the expression of receptors, CXCR4 and CXCR7, on tumor cell membrane increases .Statistical analysis showed that CXCL14 expression of stem cell mobilized donors was significantly high. Logistic regression analysis showed that increased expression of cxcl14 might hinder MDS progression, and overexpression of CXCL12 / CXCR4 axis was beneficial to disease progression. Kaplan-meier survival analysis showed that the median survival time and cumulative survival rate of patients with high CXCL14 expression were both better than the low CXCL14 expression group's. In the CXCL14 low-expression group, the gene promoter was hypermethylated.The expression of CXCR4 and CXCR7 on the surface of cell SKM-1 was down-regulated after Descitabine treatment, similarly in CXCL14 overexpression. In vitro, the high expression of CXCL14 could inhibit cell SKM-1 proliferation and promote cell apoptosis, and weak the cell migration and invasion induced by CXCL12/CXCR4 axis.Conclusion: In MDS, up-regulating CXCL14 expression might is one of the key factors to prevent the excessive activation of CXCL12 /CXCR4 axis, to maintain the stem cells in dynamic balance and limit the migration of tumor cells. To stimulate CXCL14 in vivo and infusion CXCL14 analogues are expected to be a new way in MDS treatment.

Disclosures

No relevant conflicts of interest to declare.
Tumor Lysis Syndrome Management in Community Oncology Settings
Authors: Howard Scott
Published: November 2019

Background

Tumor lysis syndrome (TLS) can complicate the management of patients with bulky chemosensitive cancers. TLS incidence and severity are increasing with new highly effective agents for hematologic cancers. However, prophylaxis and management vary widely, even within the same center.

Methods

We examined TLS management and outcomes from records of 14383 newly-diagnosed adults with lymphoma treated from 2010- 2019 at 110 member hospitals of the Guardian Research Network (GRN, www.GuardianResearch.org), a non-profit community oncology consortium with a database containing patients' entire medical, including all demographics, diagnoses, labs, medications, procedures, encounters, and notes of all kinds (clinical, radiology reports). Anonymized, de-identified data about demographics, diagnosis, treatment, supportive care, and outcomes was analyzed to determine patterns of TLS management in the community setting. Natural language processing was used to identify clinicians' references to tumor lysis syndrome, risk assessment, and cancer bulk.

Results

Of 529784 cancer patients in the Guardian Research Network database, there were 14383 newly-diagnosed adults with lymphoma, of whom 81% received no uric acid lowering therapy, 17% received allopurinol or febuxostat, and only 2% received Rasburicase. TLS management varied by region: 11% of patients in Virginia received uric acid lowering therapy vs 26% in South Carolina (p<0.001) and lymphoma subtype: 11% Hodgkin lymphoma, 26% B-cell non-Hodgkin lymphomas, p<0.001). Acute kidney injury (AKI) occurred in 4.3% of patients and logistic regression confirmed NHL (versus Hodgkin), black race (versus white), and older age as risk factors (p<0.01 for each). 216 patients (1.5%) died within 30 days. Of special note, bone marrow infiltration in acute leukemia patients was not noted as a site of bulky disease, despite the fact that a marrow with 50% infiltration of leukemic cells typically contains 700 grams of cancer, and represents bulky disease that places the patient at significant risk for TLS if treated with highly active agents.

Conclusions

Early acute kidney injury is common in patients with B-cell lymphomas. Assessment of TLS risk and prophylaxis is warranted, especially when using new, highly effective chemotherapy agents in patients with bulky disease. Assessment of tumor bulk was rarely documented in the medical records.

Table

Disclosures

Howard: BTG: Consultancy, Research Funding; EUSA Pharma: Consultancy; Sanofi: Consultancy, Speakers Bureau; Servier: Consultancy, Speakers Bureau; Amgen: Honoraria.
Hospital mortality in acute coronary syndrome: adjustment of GRACE score by D-dimer enables a more accurate prediction in a prospective cohort study
Authors: Yu Tongtong , Jiao Yundi , Song Jia , He Dongxu , Wu Jiake , Sun Zhijun , Sun Zhaoqing
Published: November 2019

Backgroud

To assess the value of D-dimer and its combination with The Global Registry of Acute Coronary Events (GRACE) score in predicting in-hospital mortality in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI).

Methods

In 5923 ACS patients undergoing PCI, the role of D-dimer and the added value of D-dimer to GRACE score for predicting in-hospital mortality were tested.

Results

After multivariable adjustment, D-dimer could significantly predict in-hospital mortality. Also, it could significantly improve the prognostic performance of GRACE score (C-statistic: z = 2.269, p = 0.023; IDI: 0.016, p = 0.032; NRI: 0.291, p = 0.035).

Conclusion

In patients with ACS undergoing PCI, D-dimer was an independent predictor of in-hospital death. It could also improve the prognostic performance of GRACE score.
Cross-sectional associations between personality traits and device-based measures of step count and sedentary behaviour in older age: the Lothian Birth Cohort 1936
Authors:   on behalf of the Seniors USP Team, Čukić Iva , Gale Catharine R. , Chastin Sebastien F. M. , Dall Philippa M. , Dontje Manon L. , Skelton Dawn A. , Deary Ian J.
Published: November 2019

Background

While the associations between personality traits and self-reported physical activity are well replicated, few studies have examined the associations between personality and device-based measures of both physical activity and sedentary behaviour. Low levels of physical activity and high levels of sedentary behaviour are known risk factors for poorer health outcomes in older age.

Methods

We used device-based measures of physical activity and sedentary behaviour recorded over 7 days in 271 79-year-old participants of the Lothian Birth Cohort 1936. Linear regression models were used to assess whether personality traits were cross-sectionally associated with step count, sedentary time, and the number of sit-to-stand transitions. Personality traits were entered one at a time, and all-together, controlling for age and sex in Model 1 and additionally for BMI and limiting long-term illness in Model 2.

Results

None of the associations between personality traits and measures of physical activity and sedentary behaviours remained significant after controlling for multiple-comparisons using the False Discovery Rate test (all ps > .07).

Conclusions

We found no evidence that personality traits are associated with device-based measures of physical activity or sedentary behaviour in older age. More studies are needed to replicate and examine the nature of these relationships.
Native aortic valve endocarditis with Morganella morganii in a patient with multiple myeloma and valvular amyloidosis: a case report
Authors: van Bentum Renée , Nieken Judith , de Waal Esther , Hoogendoorn Mels
Published: November 2019

Background

Patients with multiple myeloma (MM) are known to be immune incompetent and experience higher incidences of infectious diseases. However, infective endocarditis (IE) is rarely observed in patients with MM andMorganella morganii (M. morganii) has rarely been associated with IE.

Case presentation

A 72-year-old female receiving 4th line treatment for MM presented with fever and concomitant confusion. Urinary culture revealed growth ofEscherichia coli, wherefore broadspectrum penicillin and high-dose corticosteroids were initiated. However, blood cultures showed growth ofM. morganii. Fluoroquinolone was added due to penicillin-resistance of theMorganellaspecies. Two days after admission, the patient acutely deteriorated with hemodynamic instability. Gentamicin and high dose corticosteroids were added. Echocardiography showed marked aortic valve vegetation with severe aortic valve regurgitation, leading to the diagnosis of bacterial endocarditis of the native aortic valve. Shortly after diagnosis, the patient died. At autopsy, vegetation with gram-negative rods in the native aortic valve was observed, confirming the diagnosis ofM. morganii-endocarditis. Additional staining for amyloid confirmed advanced light-chain (AL) amyloidosis with extensive amyloid depositions of the aortic valve and valvular damage as complications of her MM.

Conclusions

Our case suggests that IE withM. morganiiwas facilitated by the combination of the cardiac amyloidosis with valvular impairment and the profound immune deficiency caused by the several chemo-immunomodulatory treatment lines and the MM itself. This case further illustrates that awareness for rare opportunistic infections in an era with growing potential of combined chemoimmunotherapy is warranted.
Ruxolitinib shows activity against Hodgkin lymphoma but not primary mediastinal large B-cell lymphoma
Authors: Kim Seok Jin , Yoon Dok Hyun , Kang Hye Jin , Hong Jung Yong , Lee Ho Sup , Oh Sung Yong , Shin Ho-Jin , Kong Jee Hyun , Yi Jun Ho , Sakamoto Kana , Ko Young Hyeh , Huh Jooryung , Lee Seung-Sook , Takeuchi Kengo , Shin Dong-Yeop , Suh Cheolwon , Kim Won Seog
Published: November 2019

Background

The upregulated expression of the JAK/STAT pathway promotes tumor growth in Hodgkin lymphoma (HL) and primary mediastinal large B-cell lymphoma (PMBCL). Based on the hypothesis that JAK2 is a therapeutic target, we performed a prospective pilot study using ruxolitinib.

Methods

Relapsed or refractory patients with HL or PMBCL were eligible for this study, and JAK2 amplification was assessed by fluorescence in situ hybridization. Ruxolitinib was administered orally at a dose of 20 mg twice daily for a 28-day cycle. Treatment was continued for up to 16 cycles or until progressive disease or intolerability. The primary objective was to assess the overall disease control rate comprising complete response (CR), partial response (PR), or stable disease (SD).

Results

We analyzed 13 HL patients and six PMBCL patients. All responders (one CR, five PR, and one SD) had HL whereas all cases of PMBCL progressed after first or second cycle. The disease control rate for HL was 54% (7/13) with median response duration of 5.6 months. JAK2 amplification was present in six of nine patients tested (four HL, two PMBCL), and three of these HL patients showed PR (n = 2) or SD (n = 1). None of the three HL patients shown to not have JAK2 amplification responded to ruxolitinib. Most treatment-related adverse events were grade 1 or 2 and manageable.

Conclusions

Ruxolitinib has single-agent activity against HL but does not act against PMBCL with or without JAK2 amplification.

Trial registration

The study population was patients who had relapsed or refractory HL or PMBCL, and patients were registered for our pilot study after providing written informed consent between November 2013 and November 2015 (CilinicalTrials.gov: NCT01965119).
A rare content of congenital inguinal hernia: a case report of splenogonadal fusion
Authors: Xiang Xi , Jiang Yong , Liu Ju-xian , Qiu Li
Published: November 2019

Background

Splenogonadal fusion (SGF) is a rare congenital malformation that occurs during embryonic development. SGF typically presents as a left-sided scrotal swelling, left inguinal hernia, scrotal mass, or cryptorchidism. Therefore, it is easily misdiagnosed, and unnecessary orchiectomy may occur. This study aimed to report a rare case of SGF.

Case presentation

A 5-month-old male child presented with a history of obvious left scrotal swelling for 1 month, which progressively worsened 10 h before the hospital visit. The ultrasound examination exhibited a solid mass in the left scrotum, with echo quite similar to that in the testicle and went up into the abdominal cavity through an identical echogenic band structure. After surgical resection, the pathological examination confirmed that the submitted tissue was spleen tissue with extensive bleeding.

Conclusion

Ultrasound can provide important information regarding the diagnosis of SGF. The possibility of SGF should be considered for further differential diagnosis in the case of similar patients.
The impact of interventions for youth experiencing homelessness on housing, mental health, substance use, and family cohesion: a systematic review
Authors: Wang Jean Zhuo , Mott Sebastian , Magwood Olivia , Mathew Christine , Mclellan Andrew , Kpade Victoire , Gaba Priya , Kozloff Nicole , Pottie Kevin , Andermann Anne
Published: November 2019

Background

Youth often experience unique pathways into homelessness, such as family conflict, child abuse and neglect. Most research has focused on adult homeless populations, yet youth have specific needs that require adapted interventions. This review aims to synthesize evidence on interventions for youth and assess their impacts on health, social, and equity outcomes.

Methods

We systematically searched Medline, Embase, PsycINFO, and other databases from inception until February 9, 2018 for systematic reviews and randomized controlled trials on youth interventions conducted in high income countries. We screened title and abstract and full text for inclusion, and data extraction were completed in duplicate, following the PRISMA-E (equity) review approach.

Results

Our search identified 11,936 records. Four systematic reviews and 18 articles on randomized controlled trials met the inclusion criteria. Many studies reported on interventions including individual and family therapies, skill-building, case management, and structural interventions. Cognitive behavioural therapy led to improvements in depression and substance use, and studies of three family-based therapies reported decreases in substance use. Housing first, a structural intervention, led to improvements in housing stability. Many interventions showed inconsistent results compared to services as usual or other interventions, but often led to improvements over time in both the intervention and comparison group. The equity analysis showed that equity variables were inconsistently measured, but there was data to suggest differential outcomes based upon gender and ethnicity.

Conclusions

This review identified a variety of interventions for youth experiencing homelessness. Promising interventions include cognitive behavioural therapy for addressing depression, family-based therapy for substance use outcomes, and housing programs for housing stability. Youth pathways are often unique and thus prevention and treatment may benefit from a tailored and flexible approach.
Are changes in radiological leg alignment and femoral parameters after total hip replacement responsible for joint loading during gait?
Authors: van Drongelen Stefan , Kaldowski Hanna , Tarhan Timur , Assi Ayman , Meurer Andrea , Stief Felix
Published: November 2019

Background

Gait kinematics after total hip replacement only partly explain the differences in the joint moments in the frontal plane between hip osteoarthritis patients after hip replacement and healthy controls. The goal of this study was to determine if total hip replacement surgery affects radiological leg alignment (Hip-Knee-Shaft-Angle, femoral offset, Neck-Shaft-Angle and varus/valgus alignment) and which of these parameters can explain the joint moments, additionally to the gait kinematics.

Methods

22 unilateral hip osteoarthritis patients who were scheduled for total hip replacement were included in the study. Preoperatively and 1 year postoperatively all patients had biplanar radiographic examinations and 3D gait analysis.

Results

The operated leg showed significantly (P < 0.05) more varus (1.1°) as well as a larger femoral offset (+ 8 mm) and a larger Hip-Knee-Shaft-Angle (+ 1.3°) after total hip replacement; however no significant differences in the joint moments in the frontal plane compared to healthy controls were found. The hip moment (first half of stance) and the knee moments (first and second half of stance) were mostly determined by the varus/valgus alignment (29% and respectively 36% and 35%). The combination with a kinematic parameter (knee range of motion, foot progression angle) increased the predictive value for the knee moments.

Conclusion

In our patient group the joint moments after total hip replacement did not differ from healthy controls, whereas radiological leg alignment parameters changed significantly after the total hip replacement. A combination of these radiological leg parameters, especially the varus alignment, and the deviating kinematics explain the joint moments in the frontal plane during gait after total hip replacement surgery. For surgeons it is important not to create too much of a structural varus alignment by implanting the new hip joint as varus alignment can increase the knee adduction moment and the risk for osteoarthritis of the medial knee compartment.

Trial registration

This study was retrospectively registered with DRKS (German Clinical Trials Register) under the number DRKS00015053. Registered 1st of August 2018.
Associations between pressure pain threshold in the neck and postural control in patients with dizziness or neck pain – a cross-sectional study
Authors: Knapstad Mari K. , Goplen Frederik K. , Ask Tove , Skouen Jan S. , Nordahl Stein Helge G.
Published: November 2019

Background

It is theorized that neck pain may cause reduced postural control due to the known physiological connection between the receptors in the cervical spine and the vestibular system. The purpose of this study was to examine whether the pressure pain threshold in the neck is associated with postural sway in patients with dizziness or neck pain.

Methods

Consecutive patients with dizziness (n = 243) and neck pain (n = 129) were recruited from an otorhinolaryngological department and an outpatient spine clinic, respectively. All subjects underwent static posturography. Pressure pain thresholds were measured at four standardized points in the neck, and generalized pain was assessed using the American College of Rheumatology tender points. The relationship between postural sway and pressure pain threshold was analyzed by linear regression, and the covariates included age, sex, and generalized pain.

Results

In the dizzy group, there was a small, inverse relationship between pressure pain thresholds and sway area with eyes closed, after adjusting for age, sex, and generalized pain (bare platform; lower neck, p = 0.002, R2 = 0.068; upper neck, p = 0.038, R2 = 0.047; foam rubber mat; lower neck, p = 0.014, R2 = 0.085). The same inverse relationship was found between pressure pain thresholds in the neck and the Romberg ratio on a bare platform after adjusting for age, sex and generalized pain (upper neck, p = 0.15, R2 = 0.053; lower neck, p = 0.002, R2 = 0.069). Neither of these relationships were present in the neck pain group.

Conclusion

Our findings indicate that the pressure pain threshold in the neck is associated with postural sway in patients suffering from dizziness after adjusting for age, sex, and generalized pain, but only with closed eyes. The association was small and should be interpreted with caution.

Trial registration

Trial registration: Clinicaltrial.gov NCT03531619. Retrospectively registered 22 May 2018.
Defining ‘actionable’ high- costhealth care use: results using the Canadian Institute for Health Information population grouping methodology
Authors: Anderson Maureen , Revie Crawford W. , Stryhn Henrik , Neudorf Cordell , Rosehart Yvonne , Li Wenbin , Osman Meriç , Buckeridge David L. , Rosella Laura C. , Wodchis Walter P.
Published: November 2019

Background

A small proportion of the population consumes the majority of health care resources. High-cost health care users are a heterogeneous group. We aim to segment a provincial population into relevant homogenous sub-groups to provide actionable information on risk factors associated with high-cost health care use within sub-populations.

Methods

The Canadian Institute for Health Information (CIHI) Population Grouping methodology was used to define mutually exclusive and clinically relevant health profile sub-groups. High-cost users (> = 90th percentile of health care spending) were defined within each sub-group. Univariate analyses explored demographic, socio-economic status, health status and health care utilization variables associated with high-cost use. Multivariable logistic regression models were constructed for the costliest health profile groups.

Results

From 2015 to 2017, 1,175,147 individuals were identified for study. High-cost users consumed 41% of total health care resources. Average annual health care spending for individuals not high-cost were $642; high-cost users were $16,316. The costliest health profile groups were ‘long-term care’, ‘palliative’, ‘major acute’, ‘major chronic’, ‘major cancer’, ‘major newborn’, ‘major mental health’ and ‘moderate chronic’. Both ‘major acute’ and ‘major cancer’ health profile groups were largely explained by measures of health care utilization and multi-morbidity. In the remaining costliest health profile groups modelled, ‘major chronic’, ‘moderate chronic’, ‘major newborn’ and ‘other mental health’, a measure of socio-economic status, low neighbourhood income, was statistically significantly associated with high-cost use.

Interpretation

Model results point to specific, actionable information within clinically meaningful subgroups to reduce high-cost health care use. Health equity, specifically low socio-economic status, was statistically significantly associated with high-cost use in the majority of health profile sub-groups. Population segmentation methods, and more specifically, the CIHI Population Grouping Methodology, provide specificity to high-cost health care use; informing interventions aimed at reducing health care costs and improving population health.
Terminalia Arjuna bark extract impedes foam cell formation and promotes apoptosis in ox-LDL-stimulated macrophages by enhancing UPR-CHOP pathway
Authors: Bhansali Shipra , Khatri Shivani , Dhawan Veena
Published: November 2019

Background

Increased macrophage and foam cell apoptosis during early atherogenesis retards plaque progression by impeding foam cell formation, suppressing inflammation and limiting lesion cellularity. Our previous in vitro study in THP1 macrophages demonstrated that Terminalia Arjuna (TA) attenuates dual-specificity phosphatase1 (DUSP1), a key negative regulator of JNK/P38MAPK signaling cascade, the branch also implicated in the UPR (unfolded protein response)-CHOP-mediated apoptotic pathway; however this pathway has not been explored so far in the presence of TA. Therefore, we aimed to elucidate the pro-apoptotic effect of aqueous bark extract of TA (aqTAE) on macrophage and foam cells and the underlying mechanism associated with it.

Methods

THP1 cells were initially differentiated into macrophages with phorbol-12-myristate-13-acetate (PMA) (100 ng/ml) for 24 h, followed by ox-LDL (100 μg/ml) treatment for another 24 h to induce foam cell formation. Thereafter, macrophages and ox-LDL- treated cells were incubated with aqTAE (100 μg/ml) for the next 24 h. Further, Oil Red O (ORO) staining, CD36 expression profiling, apoptotic assay and transcriptional and translational expression of ER-stress markers i.e., X-box binding protein 1 (XBP1) and C/EBP homologous protein (CHOP) were performed for elucidating the potential mechanism underlying TA-induced macrophage and foam cell apoptosis.

Results

We demonstrated that ox-LDL treatment significantly increased lipid accumulation and upregulated CD36 expression, indicating foam cell formation; while the addition of aqTAE resulted in a significant decline in ORO positive cells, and suppression of CD36 expression in ox-LDL-stimulated macrophages, suggestive of reduced formation of lipid-laden foam cells. Further, aqTAE treatment alone and in combination with oxidized low-density lipoprotein (ox-LDL) stimulus, significantly attenuated CD36 expression; increased apoptosis; and augmented the expression of UPR regulatory proteins including XBP1 and CHOP, and similar observations were noted when cells were treated with ox-LDL alone. These findings indicate that TA promotes macrophage and foam cell apoptosis via enhancing UPR-mediated activation of JNK/p38MAPK-CHOP pathway in a DUSP1-dependent manner, implying a possible interplay between ox-LDL-induced ER stress- and TA-mediated MAPK signaling.

Conclusion

Our data shows that aqTAE inhibits foam cell formation, as well as promotes macrophage and foam cell apoptosis by augmenting UPR- JNK/p38MAPK-CHOP signaling cascade via inhibiting DUSP1. These findings provide novel mechanistic insight into the anti-atherogenic potential of TA, which may prove beneficial against early-stage atherosclerotic lesions.
Upregulation of cannabinoid receptor type 2, but not TSPO, in senescence-accelerated neuroinflammation in mice: a positron emission tomography study
Authors: Yamagishi Satoru , Iga Yurika , Nakamura Masato , Takizawa Chika , Fukumoto Dai , Kakiuchi Takeharu , Nishiyama Shingo , Ohba Hiroyuki , Tsukada Hideo , Sato Kohji , Ouchi Yasuomi
Published: November 2019

Background

Microglial cells are activated in response to changes in brain homeostasis during aging, dementia, and stroke. Type 2 endocannabinoid receptors (CB2) and translocator protein 18 kD (TSPO) are considered to reflect distinct aspects of microglia-related neuroinflammatory responses in the brain. CB2 activation is considered to relate to the neuroprotective responses that may occur predominantly in the early stage of brain disorders such as Alzheimer’s disease, while an increase in TSPO expression tends to occur later during neuroinflammation, in a proinflammatory fashion. However, this information was deduced from studies with different animal samples under different experimental settings. In this study, we aimed to examine the early microglial status in the inflammation occurring in the brains of senescence-accelerated mouse prone 10 (SAMP10) mice, using positron emission tomography (PET) with CB2 and TSPO tracers, together with immunohistochemistry.

Methods

Five- and 15-week-old SAMP10 mice that undergo neurodegeneration after 7 months of age were used. The binding levels of the TSPO tracer (R)-[11C]PK11195 and CB2 tracer [11C]NE40 were measured using PET in combination with immunohistochemistry for CB2 and TSPO. To our knowledge, this is the first study to report PET data for CB2 and TSPO at the early stage of cognitive impairment in an animal model.

Results

The standard uptake value ratios (SUVRs) of [11C]NE40 binding were significantly higher than those of (R)-[11C]PK11195 binding in the cerebral cortical region at 15 weeks of age. At 5 weeks of age, the [11C]NE40 SUVR tended to be higher than the (R)-[11C]PK11195 SUVR. The (R)-[11C]PK11195 SUVR did not significantly differ between 5- and 15-week-old mice. Consistently, immunostaining analysis confirmed the upregulation of CB2, but not TSPO.

Conclusions

The use of the CB2 tracer [11C]NE40 and/or an immunohistochemical approach allows evaluation of the role of microglia in acute neuroinflammatory processes in the early stage of neurodegeneration. The present results provide in vivo evidence of different responses of two types of microglia to senescence-accelerated neuroinflammation, implying the perturbation of microglial balance by aging. Specific treatment for CB2-positive microglia might help ameliorate senescence-related neuroinflammation and the following neurodegeneration.
Paclitaxel-activated astrocytes produce mechanical allodynia in mice by releasing tumor necrosis factor-α and stromal-derived cell factor 1
Authors: Liu Xiaojuan , Tonello Raquel , Ling Yuejuan , Gao Yong-Jing , Berta Temugin
Published: November 2019

Background

Paclitaxel is a widely used and potent chemotherapeutic agent for the treatment of cancer. However, patients receiving paclitaxel often develop an acute pain syndrome for which there are few treatment options. Astrocytes play an important role in the pathogenesis of pain in multiple preclinical models, as well as in paclitaxel-treated rodents. However, it is still unclear what the exact contribution of astrocytes may be in paclitaxel-associated acute pain syndrome (P-APS).

Methods

P-APS was modeled by a single systemic or intrathecal injection of paclitaxel and astrocyte contribution tested by immunohistochemical, pharmacological, and behavioral approaches. Cell cultures were also prepared to assess whether paclitaxel treatment directly activates astrocytes and whether intrathecal injection of paclitaxel-treated astrocytes produces pain that is reminiscent of P-APS.

Results

Systemic injection of paclitaxel resulted in increased expression of glial fibrillary acidic protein (a common marker of astrocytic activation), as well as both systemic or intrathecal injection of paclitaxel induced pain hypersensitivity indicated by the development of mechanical allodynia, which was significantly reversed by the astrocytic inhibitor L-α-AA. Cultured astrocytes were activated by paclitaxel with significant increases in protein levels for tumor necrosis factor-α (TNF-α) and stromal-derived cell factor 1 (SDF-1). Importantly, intrathecal injection of paclitaxel-activated astrocytes produced mechanical allodynia that was reversed by TNF-α and SDF-1 neutralizing antibodies.

Conclusion

Our results suggest for the first time that paclitaxel can directly activate astrocytes, which are sufficient to produce acute pain by releasing TNF-α and SDF-1. Targeting astrocytes and these cytokines may offer new treatments for P-APS.
Radiographic analysis of subclinical appearances of the hip joint among patients with labral tears
Authors: Aiba Hisaki , Watanabe Nobuyuki , Fukuoka Muneyoshi , Wada Ikuo , Murakami Hideki
Published: November 2019

Objective

Labral tears can be complicated by hip diseases, including osteoarthritis or femoral acetabular impingement. To accurately plan hip arthroscopy or subsequent conversion to total hip arthroplasty, the presence of bony abnormalities in the hip joint must be evaluated. This study aimed to elucidate the utility of multiplanar reconstruction computed tomography (mCT) for the detection of subclinical coincidence of osteoarthritis or femoral acetabular impingement with a labrum tear.

Materials and methods

We retrospectively analysed 34 patients (36 hips) with labrum tears without apparent osteoarthritis or hip dysplasia from 2012 to 2015. The joint spaces were calculated using radiographs or mCT, and the detection rates of degenerative cyst and herniation pit were compared.

Results

Narrow joint spaces (< 2 mm) were more clearly detected in mCT (p < 0.05, chi-square analysis) than in radiographs. The detection rate of cysts in the acetabulum was 8.3% using radiographs and 36.1% using mCT (p < 0.001, chi-square analysis). Additionally, the detection of herniation pit was 8.3% and 25.0% using radiographs and mCT, respectively (p = 0.053, chi-square analysis).

Conclusion

We performed the radiographic analysis of patients with labral tears using radiographs and mCT. The mCT allowed for fine detection of narrow joint spaces and subtle subclinical appearances. The results of this study may provide surgeons with more appropriate strategies for the treatment of labral tears.
Pathophysiology of and therapeutic options for a GABRA1 variant linked to epileptic encephalopathy
Authors: Bai Yun-Fei , Chiu Michelle , Chan Elizabeth S. , Axerio-Cilies Peter , Lu Jie , Huh Linda , Connolly Mary B. , Guella Ilaria , Farrer Matthew J. , Xu Zhi-Qing David , Liu Lidong , Demos Michelle , Wang Yu Tian
Published: November 2019

We report the identification of a de novo GABRA1 (R214C) variant in a child with epileptic encephalopathy (EE), describe its functional characterization and pathophysiology, and evaluate its potential therapeutic options. The GABRA1 (R214C) variant was identified using whole exome sequencing, and the pathogenic effect of this mutation was investigated by comparing wild-type (WT) α1 and R214C α1 GABAA receptor-expressing HEK cells. GABA-evoked currents in these cells were recorded using whole-cell, outside-out macro-patch and cell-attached single-channel patch-clamp recordings. Changes to surface and total protein expression levels of WT α1 and R214C α1 were quantified using surface biotinylation assay and western blotting, respectively. Finally, potential therapeutic options were explored by determining the effects of modulators, including diazepam, insulin, and verapamil, on channel gating and receptor trafficking of WT and R214C GABAA receptors. We found that the GABRA1 (R214C) variant decreased whole-cell GABA-evoked currents by reducing single channel open time and both surface and total GABAA receptor expression levels. The GABA-evoked currents in R214C GABAA receptors could only be partially restored with benzodiazepine (diazepam) and insulin. However, verapamil treatment for 24 h fully restored the function of R214C mutant receptors, primarily by increasing channel open time. We conclude that the GABRA1 (R214C) variant reduces channel activity and surface expression of mutant receptors, thereby contributing to the pathogenesis of genetic EE. The functional restoration by verapamil suggests that it is a potentially new therapeutic option for patients with the R214C variant and highlights the value of precision medicine in the treatment of genetic EEs.
On the Boussinesq system: local well-posedness of the strong solution and inviscid limits
Authors: Guo Lianhong , Li Yuanfei , Hou Chunjuan
Published: November 2019

In this paper, we consider the solvability, regularity and vanishing viscosity limit of the 3D viscous Boussinesq equations with a Navier-slip boundary condition. We also obtain the rate of convergence of the solution of viscous Boussinesq equations to the corresponding ideal Boussinesq equations.
Graph convolutional networks: a comprehensive review
Authors: Zhang Si , Tong Hanghang , Xu Jiejun , Maciejewski Ross
Published: November 2019

Graphs naturally appear in numerous application domains, ranging from social analysis, bioinformatics to computer vision. The unique capability of graphs enables capturing the structural relations among data, and thus allows to harvest more insights compared to analyzing data in isolation. However, it is often very challenging to solve the learning problems on graphs, because (1) many types of data are not originally structured as graphs, such as images and text data, and (2) for graph-structured data, the underlying connectivity patterns are often complex and diverse. On the other hand, the representation learning has achieved great successes in many areas. Thereby, a potential solution is to learn the representation of graphs in a low-dimensional Euclidean space, such that the graph properties can be preserved. Although tremendous efforts have been made to address the graph representation learning problem, many of them still suffer from their shallow learning mechanisms. Deep learning models on graphs (e.g., graph neural networks) have recently emerged in machine learning and other related areas, and demonstrated the superior performance in various problems. In this survey, despite numerous types of graph neural networks, we conduct a comprehensive review specifically on the emerging field of graph convolutional networks, which is one of the most prominent graph deep learning models. First, we group the existing graph convolutional network models into two categories based on the types of convolutions and highlight some graph convolutional network models in details. Then, we categorize different graph convolutional networks according to the areas of their applications. Finally, we present several open challenges in this area and discuss potential directions for future research.
Combining qualitative research with PPI: reflections on using the person-based approach for developing behavioural interventions
Authors: Muller Ingrid , Santer Miriam , Morrison Leanne , Morton Kate , Roberts Amanda , Rice Cathy , Williams Marney , Yardley Lucy
Published: November 2019

Background

The value and importance of qualitative research and Patient and Public Involvement (PPI) for developing complex health interventions is widely recognised. However, there is often confusion between the two, with researchers relying on just one of these approaches, rather than using the two alongside one another.

Methods

The Person-Based Approach (PBA) to developing health-related behaviour change interventions adapts and integrates methods from user-centred design and qualitative research. The PBA involves qualitative research at multiple stages of interventions to ensure they are acceptable, feasible, meaningful, and optimally engaging to the people who will use them. The qualitative research is carried out with research participants from a target population, who have no prior or continuing involvement in the wider research process and see the intervention from a fresh perspective. This enables in-depth understanding of the views and experiences of a wide range of target users and the contexts within which they engage with behavioural change.

PPI in research is carried out with or by members of the public and is a key part of the research process. PPI contributors are involved at all stages of research design and interpretation. PPI provides input into interventions as members of the research team alongside other stakeholders, such as health professionals and behaviour change experts.

Results

We advocate using qualitative research alongside PPI at all stages of intervention planning, development, and evaluation. We illustrate this with examples from recent projects developing complex health interventions, highlighting examples where PPI and PBA have pulled in different directions and how we have approached this, how PPI have helped optimise interventions based on PBA feedback, and how we have engaged PPI in community settings.

Conclusions

PPI provides a valuable alternative to the traditional researcher-led approaches, which can be poorly matched to the needs of target users. Combining PPI with the PBA can help to create optimally engaging interventions by incorporating a greater diversity of feedback than would have been possible to achieve through PPI or qualitative approaches alone.
Effect of tungsten on the oxidation of alumina-forming austenitic stainless steel
Authors: Kang Jun-Yun , Ha Heon-Young , Kim Sung-Dae , Park Jun Young , Jang Min-Ho , Lee Tae-Ho
Published: November 2019

As more W replaced Mo in alumina-forming austenitic stainless steels, weight gain by oxidation decreased after 336 h at 1053 K. Electron microscopy revealed slower growth of scale in the presence of more numerous second phases by W addition. The retardation of oxidation was attributed to the necessary partitioning of W in front of the metal-oxide interface. The W-rich second phases interacted with growing oxides and finally transformed to fine particles of metallic W alloy within the scale.
One-step synthesis of Pt/a-CoOx core/shell nanocomposites
Authors: Kim Daewoon , Kim Sung Joo , Yuk Jong Min
Published: November 2019

Herein, we synthesize a core/shell Pt/a-CoOx nanocomposite via one-step synthesis using a strong reaction agent of borane t-butylamine(BBA) at 200 °C. Transmission electron microscopy study shows that the morphology of nanocomposites is controlled by the stirring time and perfect core/shell structure is formed with over 7 days stirring time.
The effect of early versus late lipid infusion in parenteral nutrition on the biochemical and cortical auditory evoked potential parameters in preterm neonates
Authors: Abdou Rania Mohamed , Weheiba Hoda Mahmoud Ibrahim
Published: November 2019

Background

As brain activity depends greatly on the functions provided by lipid membranes, dietary fat in early life can affect the developing nervous system. Despite the adoption of an early more aggressive parenteral nutrition approach with amino acid infusions still reluctance to the early use of intravenous lipids in neonates.

Aim

To compare the effect of delayed versus early introduction of intravenous lipid in preterm on the biochemical parameters and on brain development by the cortical auditory evoked potential (CAEP) latency and amplitude.

Methods

This is a comparative study included 49 neonates admitted at the ain shams university NICUs. Participants were divided into two groups: 26 in group of early lipid infusion and 23 in late lipid infusion, Demographic data, and biochemical parameters were documented during the 1st 2 weeks of life. The CAEP was performed at age of 6 months. The latency and amplitude of P1 were recorded and compared between both groups.

Results

In the present work we found that group of early lipid infusion had reach their full oral intake earlier with shorter duration of parenteral nutrition and length of stay. They had better weight gain and significantly better glucose level control than group of late lipid infusion. There was no significant difference in the other chemical parameters between both groups expect for the higher incidence of cholestasis in the group of late lipid infusion. At 6 months of age, the group of early lipid infusion had significantly shorter latency and amplitude of P1 than the group of late lipid infusion.

Conclusion

Early effective nutrition positively affect feeding tolerance and weight gain and maturation of higher brain centers brain.
The role of artificial intelligence in medical imaging research
Authors: Tang Xiaoli
Published: November 2019

Without doubt, artificial intelligence (AI) is the most discussed topic today in medical imaging research, both in diagnostic and therapeutic. For diagnostic imaging alone, the number of publications on AI has increased from about 100–150 per year in 2007–2008 to 1000–1100 per year in 2017–2018. Researchers have applied AI to automatically recognizing complex patterns in imaging data and providing quantitative assessments of radiographic characteristics. In radiation oncology, AI has been applied on different image modalities that are used at different stages of the treatment. i.e. tumor delineation and treatment assessment. Radiomics, the extraction of a large number of image features from radiation images with a high-throughput approach, is one of the most popular research topics today in medical imaging research. AI is the essential boosting power of processing massive number of medical images and therefore uncovers disease characteristics that fail to be appreciated by the naked eyes. The objectives of this paper are to review the history of AI in medical imaging research, the current role, the challenges need to be resolved before AI can be adopted widely in the clinic, and the potential future.
Observability, Unobservability and the Copenhagen Interpretation in Dirac's Methodology of Physics
Authors: Oldofredi Andrea , Esfeld Michael
Published: November 2019

Paul Dirac has been undoubtedly one of the central figures of the last century physics, contributing in several and remarkable ways to the development of quantum mechanics; he was also at the centre of an active community of physicists, with whom he had extensive interactions and correspondence. In particular, Dirac was in close contact with Bohr, Heisenberg and Pauli. For this reason, among others, Dirac is generally considered a supporter of the Copenhagen interpretation of quantum mechanics. Similarly, he was considered a physicist sympathetic with the positivistic attitude which shaped the development of quantum theory in the 1920s. Against this background, the aim of the present essay is twofold: on the one hand, we will argue that, analyzing specific examples taken from Dirac's published works, he can neither be considered a positivist nor a physicist methodologically guided by the observability doctrine. On the other hand, we will try to disentangle Dirac's figure from the mentioned Copenhagen interpretation, since in his long career he employed remarkably different—and often contradicting—methodological principles and philosophical perspectives with respect to those followed by the supporters of that interpretation.Quanta 2019; 8: 68–87.