bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of timing of initiation of renal replacement therapy on mortality: A retrospective case–control study
Authors: Engoren Milo , Maile Michael D , Heung Michael , Blum James M , Blank Ross , Napolitano Lena M , Park Pauline K , Raghavendran Krishnan , Jewell Elizabeth S , Meldrum Craig
Published: December 2019

Purpose

To determine if earlier initiation of renal replacement therapy (RRT) is associated with improved survival in patients with severe acute kidney injury.

Methods

We performed a retrospective case–control study of propensity-matched groups with multivariable logistic regression using Akaike Information Criteria to adjust for non-matched variables in a surgical ICU in a tertiary care hospital.

Results

We matched 169 of 205 (82%) patients with new initiation of RRT (EARLY group) to 169 similar patients who did not initiate RRT on that day (DEFERRED group). Eighteen (11%) of DEFERRED eventually received RRT before discharge. By univariate analysis, ICU mortality was higher in EARLY (n = 60 (36%) vs. n = 23 (14%), p < 0.001) as was hospital mortality (n = 73 (43%) vs. n = 44 (26%), p = 0.001). Of the 18 RRT patients in DEFERRED, 12 (67%) died in ICU and 13 (72%) in hospital. After propensity matching and logistic regression, we found that EARLY initiation of RRT was associated with a more than doubling of ICU mortality (aOR = 2.310, 95% confidence interval = 1.254–4.257, p = 0.007). However, after similar adjustment, there was no difference in hospital mortality (aOR = 1.283, 95% CI = 0.753–2.186, p = 0.360).

Conclusions

While ICU mortality was increased in the EARLY group, there was no difference in hospital mortality between EARLY and DEFERRED groups.
What to consider before prescribing inhaled medications: a pragmatic approach for evaluating the current inhaler landscape
Authors: Lavorini Federico , Janson Christer , Braido Fulvio , Stratelis Georgios , Løkke Anders
Published: December 2019

Inhaled therapies are the cornerstone of treatment in asthma and chronic obstructive pulmonary disease, and there are a multitude of devices available. There is, however, a distinct lack of evidence-based guidance for healthcare providers on how to choose an appropriate inhaler. This review aims to summarise recent updates on topics related to inhaler choice, and to offer practical considerations for healthcare providers regarding currently marketed devices. The importance of choosing the right inhaler for the right patient is discussed, and the relative merits of dry powder inhalers, pressurised metered dose inhalers, breath-actuated pressurised metered dose inhalers, spacers and soft mist inhalers are considered. Compiling the latest studies in the devices therapy area, this review focuses on the most common types of handling errors, as well as the comparative rates of incorrect inhalation technique between devices. The impact of device-specific handling errors on inhaler performance is also discussed, and the characteristics that can impair optimal drug delivery, such as inhalation flow rate, inhalation volume and particle size, are compared between devices. The impact of patient perceptions, behaviours and problems with inhalation technique is analysed, and the need for appropriate patient education is also highlighted. The continued development of technology in inhaler design and the need to standardise study assessment, endpoints and patient populations are identified as future research needs.

The reviews of this paper are available via the supplemental material section.
Rheumatoid arthritis
Authors: Maru Devina , Mulla Ebrahim
Published: December 2019

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. It is characterised by symmetrical joint involvement and extra-articular manifestations. Joint and periarticular tissue destruction occurs as a result of inflammation of the synovial joints, leading to functional impairment. Early diagnosis and treatment are the key to minimising the significant daily challenges experienced by patients and underpin more successful outcomes. This article will explore the recognition and management of RA in primary care, drawing on recently updated National Institute for Health and Care Excellence guidelines.
Cytotoxic impact of a perillyl alcohol–temozolomide conjugate, NEO212, on cutaneous T-cell lymphoma in vitro
Authors: Silva-Hirschberg Catalina , Hartman Hannah , Stack Samantha , Swenson Steve , Minea Radu O. , Davitz Michael A. , Chen Thomas C. , Schönthal Axel H.
Published: December 2019

Background:

Mycosis fungoides (MF) and Sézary syndrome (SS) are subtypes of primary cutaneous lymphomas and represent complex diseases regarding their physiopathology and management. Depending on the stage of the disease, different treatment regimens are applied, but there is no consensus on an optimal approach. Prognosis for patients with early stage MF is favorable, but significantly worsens in advanced disease and in SS, where patients frequently relapse and require multiple therapies.

Methods:

We investigated the potential anticancer effects of NEO212, a novel compound generated by covalently conjugating perillyl alcohol (a natural monoterpene) to temozolomide (an alkylating agent), on MF and SS cell lines in vitro. HUT-78, HUT-102, and MyLa cells were treated with NEO212 under different conditions, and drug effects on proliferation, viability, and apoptosis were characterized.

Results:

NEO212 inhibited proliferation, diminished viability, and stimulated apoptosis in all cell lines, although with varying degrees of potency in the different cell lines. It down-regulated c-myc and cyclin D1 proteins, which are required for cell proliferation, but triggered endoplasmic reticulum stress and activation of caspases. Pretreatment of cells with antioxidants ascorbic acid and beta-mercaptoethanol prevented these NEO212-induced effects.

Conclusions:

NEO212 exerted promising anticancer effects on SS and MF cell lines. The generation of reactive oxygen species (ROS) appears to play a key role in the NEO212-induced cell death process, because the blockage of ROS with antioxidants prevented caspase activation. We propose that NEO212 should be investigated further toward clinical testing in these tumor types.
Data quality in healthcare: A report of practical experience with the Canadian Primary Care Sentinel Surveillance Network data
Authors: Ehsani-Moghaddam Behrouz , Martin Ken , Queenan John A
Published: December 2019

Data quality (DQ) is the degree to which a given dataset meets a user’s requirements. In the primary healthcare setting, poor quality data can lead to poor patient care, negatively affect the validity and reproducibility of research results and limit the value that such data may have for public health surveillance. To extract reliable and useful information from a large quantity of data and to make more effective and informed decisions, data should be as clean and free of errors as possible. Moreover, because DQ is defined within the context of different user requirements that often change, DQ should be considered to be an emergent construct. As such, we cannot expect that a sufficient level of DQ will last forever. Therefore, the quality of clinical data should be constantly assessed and reassessed in an iterative fashion to ensure that appropriate levels of quality are sustained in an acceptable and transparent manner. This document is based on our hands-on experiences dealing with DQ improvement for the Canadian Primary Care Sentinel Surveillance Network database. The DQ dimensions that are discussed here are accuracy and precision, completeness and comprehensiveness, consistency, timeliness, uniqueness, data cleaning and coherence.
Integration of the UNHCR Refugee Health Information System into the National Health Information Management System for Uganda
Authors: Kyozira Caroline , Kabahuma Catherine , Mpiima Jamiru
Published: December 2019

Background:

The Uganda Government, together with development partners, has provided continuing support services (including protection, food, nutrition, healthcare, water and sanitation) to refugee-hosting Districts to successfully manage refugees from different neighbouring countries in established settlements. This service has increased the need for timely and accurate information to facilitate planning, resource allocation and decision-making. Complexity in providing effective public health interventions in refugee settings coupled with increased funding requirements has created demands for better data and improved accountability. Health data management in refugee settings is faced with several information gaps that require harmonisation of the Ugandan National Health Management Information System (UHMIS) and United Nations High Commission for Refugees (UNHCR) Refugee Health Information System (RHIS). This article discusses the rationale for harmonisation of the UNHCR RHIS, which currently captures refugee data, with the UHMIS. It also provides insights into how refugee health data management can be harmonised within a country’s national health management information system.

Method:

A consultative meeting with various stakeholders, including the Ugandan Ministry of Health, district health teams, representatives from UNHCR, the United Nations Children Education Fund (UNICEF), United States Government and civil society organisations, was held with an aim to review the UHMIS and UNHCR RHIS health data management systems and identify ways to harmonise the two to achieve an integrated system for monitoring health service delivery in Uganda.

Results:

Several challenges facing refugee-hosting district health teams with regard to health data management were identified, including data collection, analysis and reporting. There was unanimous agreement to prioritise an integrated data management system and harmonisation of national refugee stakeholder data requirements, guided by key recommendations developed at the meeting.

Conclusion:

This article outlines a proposed model that can be used to harmonise the UNHCR RHIS with the UHMIS. The national refugee stakeholder data requirements have been harmonised, and Uganda looks forward to achieving better health data quality through a more comprehensive national UHMIS to inform policy planning and evidence-based decision-making.
Relevance of SPECT-CT in Complex Cases of Foot and Ankle Surgery: A Comparison With MRI
Authors: Claassen Leif , Yao Daiwei , Ettinger Sarah , Lerch Matthias , Daniilidis Kiriakos , Stukenborg-Colsman Christina , Plaass Christian
Published: December 2019

Background. Finding the right diagnoses in patients with complex foot and ankle disorders can be challenging. Single-photon emission computed tomography and computed tomography (SPECT-CT) has shown to be feasible in foot and ankle surgery. The aim of this study was to evaluate the reliability and accuracy of SPECT-CT and thereby its impact on final treatment decision compared with magnetic resonance imaging (MRI). Methods. A retrospective study was performed on 49 patients treated at our institution. Experienced foot and ankle surgeons independently, and blinded, analyzed clinical data and radiographs together with MRI, SPECT-CT, or a combination of both. Based on the determined final treatment decision Cohen’s kappa values were calculated to illustrate interrater and intrarater reliability. Results. The kappa values for interrater reliability were higher for SPECT-CT at .68 and MRI + SPECT-CT at .71 compared to 0.38 for MRI alone (P < .05). The kappa values for intrarater reliability of MRI + SPECT-CT were higher at .75 compared with SPECT-CT alone at .67 (P < .05) and MRI at .35 (P < .01). Conclusion. We found a higher interrater and intrarater reliability for SPECT-CT compared with MRI alone for diagnosing complex foot and ankle pathologies. SPECT-CT has a high impact on final treatment decision. The main indications are bony pathologies with diagnostic uncertainty especially in closely adjacent structures as the joints of the midfoot, occult coalitio, stress fractures, verification or exclusion of nonfusion, periprosthetic disorders after total ankle replacement and osteochondral lesion in cases of combined pathologies.

Levels of Evidence: Level IV: Retrospective study
Cavernous Thrombophlebitis Secondary to Cavernous Internal Carotid Mycotic Aneurysm
Authors: Burke Devin J. , Jadhav Ashutosh
Published: December 2019

We report a case of a 22-year-old male with a history of intravenous drug use presenting with cavernous sinus syndrome secondary to cavernous thrombophlebitis. The source of the thrombophlebitis was from a mycotic aneurysm in the setting of fungal endocarditis. With antifungal therapy and aortic valve replacement, the patient had full resolution of cranial nerve deficits. Descriptions of mycotic aneurysms of the cavernous portion of the internal carotid artery are limited to case reports and case series. Most have been nonendocarditic in etiology with poor prognosis. We present a unique case with endocarditic etiology and an excellent prognosis.
Serum adenosine deaminase activity and coronary artery disease: a retrospective case-control study based on 9929 participants
Authors: Xuan Chao , Tian Qing-Wu , Zhang Shao-Yan , Li Hui , Tian Ting-Ting , Zhao Peng , Yue Kang , Ling Yan-Yan , He Guo-Wei , Lun Li-Min
Published: December 2019

Background:

Adenosine deaminase (ADA) regulates purine metabolism through the conversion of adenosine to uric acid (UA). Adenosine and UA are closely associated with cardiovascular events, but the correlation between serum ADA activity and coronary artery disease (CAD) has not been defined.

Methods:

We performed a hospital-based retrospective case-control study that included a total of 5212 patients with CAD and 4717 sex- and age-matched controls. The serum activity of ADA was determined by peroxidase assays in an automatic biochemistry analyzer.

Results:

Serum ADA activity in the CAD group (10.08 ± 3.57 U/l) was significantly lower than that of the control group (11.71 ± 4.20 U/l, p < 0.001). After adjusting for conventional factors, serum ADA activity negatively correlated with the presence of CAD (odds ratio = 0.852, 95% confidence interval: 0.839–0.865, p < 0.001). Among the patients with CAD, serum ADA activity was lowest in patients with myocardial infarction (MI; 9.77 ± 3.80 U/l). Diabetes mellitus and hypertension increased the serum ADA activity in CAD patients.

Conclusions:

Serum ADA activity is significantly attenuated in patients with CAD, particularly in MI. We propose a mechanism by which the body maintains adenosine levels to protect the cardiovascular system in the event of CAD.
Impact of infectious diseases consultation on the outcome of patients with bacteraemia
Authors: Jiménez-Aguilar Patricia , López-Cortés Luis Eduardo , Rodríguez-Baño Jesús
Published: December 2019

Bacteraemia or bloodstream infections (BSI) are associated with much morbidity and mortality. Management of patients with bacteraemia is complex, and the increase in immunosuppressed patients and multidrug-resistant organisms poses additional challenges. The objective of this review is to assess the available published information about the impact of different aspects of management on the outcome of patients with BSI, and, specifically, the importance of infectious diseases specialists (IDS) consultation. The impact of management by IDS on different aspects, including interpretation of newer rapid techniques, early evaluation and treatment, and follow up, are reviewed. Overall, the available data suggest that IDS intervention improves the management and outcome of patients with BSI, either through consultation or structured unsolicited interventions in the context of multidisciplinary bacteraemia programmes.
Balancing impressiveness and favorability: A qualitative study on an emerging type of advertising in China
Authors: Liu Liu , Chen Huan
Published: December 2019

This study examined a new emerging advertising format (Creative Mid-Roll Advertising) in Chinese online video platforms through the eyes of consumers in order to give advertising scholars and practitioners a better understanding on how consumers perceive creative contents and formats of advertising in the era of new media. Creative Mid-Roll Advertising is a short video advertising embedded in the online TV series, and it is created in a way that makes it appear very similar to the drama in terms of the content and setting. In all, 20 in-depth interviews were conducted to collect data. Findings revealed that Creative Mid-Roll Advertising is characterized by mid-roll, native, explicit, and dramatic.
Analog Hallyu: Historicizing K-pop formations in China
Authors: Sun Meicheng , Liew Kai Khiun
Published: December 2019

This article will revisit the beginnings of the spread of Korean popular entertainment in China in the mid-1990s to early 2000s by examining the contents of previously untapped Chinese language popular entertainment magazines and public recollections on internet forums. Considered here as critical archival resources, the authors argue that these materials are instrumental in offering both new chronologies and insights to the circulatory process of the regionalization of Korean popular cultures or Hallyu. Korean popular music (hereafter K-pop) entered China after the normalization of diplomatic relations between the two countries. Instead of the often singularized, culturalist argument of “shared traditions,” this article offers a more dynamic historiography of the Korean Wave in China that is termed here as “Analog Hallyu.”
Factors Related to Longitudinal Patterns of Multiple Health Behaviors in Chinese Freshmen
Authors: Tao Shuman , Wu Xiaoyan , Zhang Yukun , Tao Fangbiao
Published: December 2019

Students with multiple health risk behaviors (HRB) have increased amount of research attention. The study aimed to examine the multiple health behaviors and whether these behaviors differ by demographic characteristics and social factors in a 1-year follow-up study among 1,989 students. All the measures were from the Youth Risk Behavior Surveillance System. Associations between demographic characteristics/social factors and multiple HRB were examined by logistic regression models. Binary logistic models indicated that females had generally higher odds of physical inactivity but lower odds of cigarette smoking, alcohol drinking, suicide attempt, and breakfast skipping. Students more than 18 years had higher odds of cigarette smoking. Physical inactivity was negatively correlated with playing school sports teams and taking extracurricular activities. Students with screen time >2 hr/d were more likely to be with physical inactivity or alcohol drinking. Logistic regression models showed that males showed higher odds of two, three, and four to six HRB at 3T. Not taking part in school sports teams/extracurricular activities and screen time >2 hr/d at baseline were risk factors of multiple HRB. Our results reveal a close association between youth risk behaviors and demographic characteristics/social factors. Health promotion interventions of co-occurred behavior should be conducted at schools.
Determinants of presidential approval ratings: Cross-country analyses with reference to Latin America
Authors: Jung Ji Won , Oh Jinhwan
Published: December 2019

Despite a conventional belief that prosperity boosts presidential popularity, research on the effect of economic and political factors on presidential popularity shows wide variation. What are the main contributing factors when people evaluate their political leaders? How do economic conditions and perception of corruption influence people’s evaluations of their political leaders? Using comprehensive, up-to-date panel data covering 20 countries, mostly from Latin America, and also including South Korea and the United States, from 1988 to 2016, this study shows that the effect of gross domestic product (GDP) growth rate and unemployment rate are strong throughout the period considered. From the year 2000, inflation and perception of corruption become significant. In highly corrupt countries, however, the significance of corruption becomes more salient, together with GDP growth rate and unemployment rate, as citizens of these countries begin to evaluate their leaders in terms of their determination to address these problems. In countries with low approval ratings, voters generally weigh GDP growth rate more heavily.
Comparing Three Established Methods for Tinnitus Pitch Matching With Respect to Reliability, Matching Duration, and Subjective Satisfaction
Authors: Neff Patrick , Langguth Berthold , Schecklmann Martin , Hannemann Ronny , Schlee Winfried
Published: December 2019

The pitch of tinnitus sound is a key characteristic that is of importance to research and sound therapies relying on exact tinnitus pitch matches. The identification of this tinnitus pitch is a challenging task as there is no objective measurement available. During the tinnitus pitch-matching procedure, the participant identifies an external sound that is most similar to the subjective perception of the tinnitus. Several methods have been developed to perform this pitch-matching procedure with tinnitus sufferers. In this study, we aimed to compare the method of adjustment, the two-alternative forced-choice (2AFC) method, and the likeness rating (LR) with respect to reliability, matching duration, and subjective satisfaction. Fifty-nine participants with chronic tinnitus were recruited and performed five consecutive runs of tinnitus matching. The participants were randomized to the three different pitch-matching methods. The intraclass correlation coefficients were .67 for method of adjustment, .63 for 2AFC, and .69 for LR, which can be interpreted as good reliability for all the three methods. However, the 2AFC method revealed significant larger within-subject variability than the other measures. Across the five runs and the three different methods, all participants learned to perform the pitch matching faster and with better self-rated accuracy. Comparing the three pitch-matching methods, LR is more time consuming and the participants were less satisfied with the 2AFC method. Overall, the three pitch-matching methods show good reliability. However, we identified differential aspects for improvement in all methods, which are discussed in this article.
Gender-wise Study of Family Climate for Adolescents in Urban India
Authors: Mishra Santwana G.
Published: December 2019

In this study, the researcher has studied the family climate for adolescents in urban society in India. The typical urban family in India has modern lifestyle and is also technologically advanced. It is believed that these families are progressive in comparison to their rural counterparts. The present research work is aimed to study the family climate of adolescents from urban families in association with their gender. A total of 309 adolescents (163 boys and 146 girls) in the age group of 14–15 years were randomly selected from the secondary schools of Aurangabad, a city in Maharashtra state of India for the academic year 2016–2017. The tool used for data collection was family climate scale (FCS) developed by Dr Beena Shah and published by National Psychological Corporation, Agra, India. In this test, family climate means an interpersonal relationship between the parents and the child. The test assesses the family climate on 10 dimensions. Data were collected by personally meeting the adolescents. The collected data were analysed using chi-squared test. The study showed that more male adolescents had favourable family climate as compared to female adolescents and the difference was significant. Also, the number of female adolescents having unfavourable family climate was significantly higher as compared to male adolescents. The study concluded that the age-old gender bias is still very much prevalent in India. The boys are favoured and given a more conducive and positive family atmosphere as compared to the girls. Hence, there is a need for creating awareness to curb this bias and help the girls in the family to be treated at par with their male counterparts.
Cholesterol Overload: Contact Sites to the Rescue!
Authors: Enrich Carlos , Rentero Carles , Grewal Thomas , Futter Clare E. , Eden Emily R.
Published: December 2019

Delivery of low-density lipoprotein-derived cholesterol to the endoplasmic reticulum (ER) is essential for cholesterol homeostasis, yet the mechanism of this transport has largely remained elusive. Two recent reports shed some light on this process, uncovering a role for Niemann Pick type-C1 protein (NPC1) in the formation of membrane contact sites (MCS) between late endosomes (LE)/lysosomes (Lys) and the ER. Both studies identified a loss of MCS in cells lacking functional NPC1, where cholesterol accumulates in late endocytic organelles. Remarkably, and taking different approaches, both studies have made a striking observation that expansion of LE/Lys-ER MCS can rescue the cholesterol accumulation phenotype in NPC1 mutant or deficient cells. In both cases, the cholesterol was shown to be transported to the ER, demonstrating the importance of ER-LE/Lys contact sites in the direct transport of low-density lipoprotein-derived cholesterol to the ER.
Rebranding of NewsHunt to Dailyhunt: Dilemma of Future Direction
Authors: Rishi Bikramjit , Kacker Archit , Hazra Syamantak
Published: December 2019

Dailyhunt’s road to the number one regional language news aggregator in India had been a long and momentous one. Virendra Gupta, CEO and founder of Dailyhunt had seen the landscape undergo multiple changes and had to adapt his company to these changes through the use of analytics and strategic partnerships with content publishers. With the rapid penetration of internet usage in India, the new users of the internet were largely expected to be individuals who would be more comfortable consuming digital content in their native language. The potential this segment held was immense and Dailyhunt was in the driver’s seat in terms of providing a personalized content stream and the large existing user base on its platform. However, with foreign investment pouring in for various new start-ups and the entry of several companies in to the segment, the challenges were set to increase, and Virendra Gupta had to decide what future strategies could help his company stand strong amidst the competition.
Survey of Literature on Measuring Logistics Cost: A Developing Country’s Perspective
Authors: Pohit Sanjib , Gupta Devendra B. , Pratap Devender , Malik Sameer
Published: December 2019

In today’s world, economic climate changes more quickly, and countries realise that globalisation has made the world small and more competitive. Also, customers seek products and services that can respond to their specific needs, and firms make effort to create competitive advantages to keep their profit and market share. All of the above trends lead firms and countries to focus on efficient logistics system. In this context, almost all developed economies and a few emerging economies estimate national logistics cost on a regular basis to understand the efficiency of their logistics system. This article makes an attempt to survey the literature on logistics cost estimation with special emphasis from the perspective of a developing country like India where estimation is a challenge due to limitation of data.

JEL Codes: D57, E23, P44
GMS Economic Corridors Under the Belt and Road Initiative
Authors: Ishida Masami
Published: December 2019

The government of China promotes the development of expressways and high-speed expressways in Greater Mekong Subregion (GMS) and tries to connect the major cities of the subregion and Kunming under the Belt and Road Initiative (BRI). First, this article reviews the development schemes in the subregion including GMS economic cooperation and the BRI. Next, it introduces the development of the transport infrastructure, including expressways and high-speed railways, connecting Kunming and Lao People’s Democratic Republic (Lao PDR), Thailand, Myanmar and Vietnam. Thereafter, it compares the total costs of the projects and how other GMS countries negotiate with China. Seeing the sections of the expressways and railways in Yunnan Province, the shares of some sections occupied by bridges and tunnels are higher than 20 per cent due to the mountainous land feature of Yunnan Province. On the other hand, the railway in Lao PDR passes through the mountainous areas, and they adopted higher specification as same as in Yunnan Province. Consequently, the debt-default risk of Lao PDR has increased. On the other hand, Thailand repeated tough negotiations with China and made efforts not to increase the total cost. The negotiations of Lao PDR and Thailand with China are illustrated in this article.

JEL Codes: O18, R10, R41, R58
Curing Ph+ ALL: assessing the relative contributions of chemotherapy, TKIs, and allogeneic stem cell transplant
Authors: Fielding Adele K.
Published: December 2019

The understanding and treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia have changed rapidly in the past 10 years. The outcome is equally as good as for Ph− disease, and with targeted tyrosine kinase inhibitor therapies in addition to chemotherapy, the novel immunotherapy approaches, and the extension of allogeneic hematopoietic stem cell transplant (allo-HCT) to older individuals, there is the potential to exceed this outcome. There is particular interest in reducing chemotherapy exposure and considering for whom allo-HCT can be avoided. However, the patient population that can help test these options in clinical trials is limited in number, and the available evidence is often derived from single-arm studies. This paper summarizes outcomes achieved with recent approaches to de novo Ph+ acute lymphoblastic leukemia in the postimatinib era and helps integrate all the available information to assist the reader to make informed choices for patients in an increasingly complex field.
Moving immunotherapy into the front line in ALL
Authors: Winters Amanda , Gore Lia
Published: December 2019

Although almost 90% of children with acute lymphoblastic leukemia (ALL) and ∼60% of children with acute myeloid leukemia are cured with frontline therapy, relapse and chemotherapy resistance are significant challenges that contribute to morbidity and mortality. Even with long-term survival, the acute and chronic burdens of therapy are major issues for patients and families. Long-term side effects occur, including cardiac, endocrinologic, neurcognitive, orthopedic, and psychosocial problems, and healthy survivorship is frequently compromised. With goals of minimizing relapse and/or decreasing traditional chemotherapy-associated toxicities, exploration of immunotherapeutic strategies has moved to the forefront in pediatric cancer. New immunotherapy approaches provide a major paradigm shift in oncology overall, often curing previously incurable patients. The past several years have yielded successful uses across a variety of malignancies, and enthusiasm continues to rise for applying these therapies more broadly. Herein we discuss current approaches incorporating the bispecific T-cell engager blinatumomab, the antibody-drug conjugate inotuzumab ozogamicin (InO), and CD19-directed chimeric antigen receptor T cells in children with relapsed/refractory B-cell ALL and discuss the potential for using these immunotherapies in the treatment of newly diagnosed children.
Osteonecrosis in sickle cell disease: an update on risk factors, diagnosis, and management
Authors: Adesina Oyebimpe O. , Neumayr Lynne D.
Published: December 2019

Osteonecrosis, a form of ischemic bone injury that leads to degenerative joint disease, affects ∼30% of people with sickle cell disease. Although osteonecrosis most commonly affects the femoral head (often bilaterally, with asymmetric clinical and radiographic progression), many people with sickle cell disease also present with multifocal joint involvement. We present the case of a young woman with bilateral osteonecrosis of the femoral head at varying stages of progression; we also highlight other important comorbid complications (eg, chronic pain requiring long-term opioids, debility, and social isolation) and postoperative outcomes. In this review, partly based on recommendations on osteonecrosis management from the 2014 evidence-based report on sickle cell disease from the National Heart, Lung and Blood Institutes, we also discuss early signs or symptoms of osteonecrosis of the femoral head, radiographic diagnosis and staging criteria, hydroxyurea effect on progression to femoral head collapse, and surgical outcomes of total hip arthroplasty in the modern era. In summary, we failed to find an association between hydroxyurea use and femoral head osteonecrosis; we also showed that evidence-based perioperative sickle cell disease management resulted in superior postoperative outcomes after cementless total hip arthroplasty in sickle cell–related osteonecrosis of the femoral head.
Lowering the boom on lower-risk myelodysplastic syndromes
Authors: Sekeres Mikkael A. , Patel Bhumika J.
Published: December 2019

Lower-risk myelodysplastic syndromes are defined using prognostic scoring systems that incorporate data on bone marrow blast percentage, degree and numbers of cytopenias, and cytogenetic abnormalities. Increasingly, these are incorporating molecular abnormalities to further refine risk. Therapy is geared toward predominating cytopenias, with erythropoiesis-stimulating agents luspatercept and lenalidomide used to ameliorate anemia, romiplostim and eltrombopag tackling thrombocytopenia, and hypomethylating agents and antithymocyte globulin palliating pancytopenia. Newer agents on the horizon are abrogating the downstream sequelae of specific molecular mutations. One challenge for the future is in further modifying response criteria to align with improvements that are clinically meaningful to patients.
Improvements in diagnosis and risk assessment of primary and secondary antiphospholipid syndrome
Authors: Petri Michelle
Published: December 2019

Classification criteria for antiphospholipid syndrome have not been updated since the revised Sapporo classification criteria were published in 2006. These criteria have limitations in that they omit nonclassical manifestations (hematologic and neurologic), include anticardiolipin and anti–β2-glycoprotein I immunoglobulin (Ig)M isotypes, and do not separately consider primary (no autoimmune disease) or secondary (usually systemic lupus erythematosus) disease. Recent findings in antiphospholipid antibody include fluctuation of antiphospholipid antibodies, recognition that IgA isotypes do confer risk, identification of the role of complementopathy in catastrophic antiphospholipid syndrome, and elucidation of the role of thrombosis risk equations.
Preoperative anemia-screening clinics
Authors: Lin Yulia
Published: December 2019

Preoperative anemia is associated with increased postoperative morbidity and mortality and with increased risk of perioperative transfusion. It is an important and modifiable risk factor for surgical patients. For high-blood-loss surgery, preoperative anemia is defined as hemoglobin <13 g/dL for both male and female patients. Preoperative anemia is common, ranging from 25% to 40% in large observational studies. The most common treatable cause of preoperative anemia is iron-deficiency anemia; the initial laboratory tests should focus on making this diagnosis. Management of iron-deficiency anemia includes iron supplementation with IV iron therapy when oral iron is ineffective or not tolerated, there is severe anemia, and there is insufficient time to surgery (<4 weeks). In other situations, erythropoiesis-stimulating agents may be considered, particularly for those patients with multiple alloantibodies or religious objections to transfusion. To facilitate the diagnosis and management of preoperative anemia, establishment of preoperative anemia-screening clinics is essential. The goals of management of preoperative anemia are to treat anemia, reduce the need for transfusion, and improve patient outcomes.
Clinical decision support and improved blood use in patient blood management
Authors: Goodnough Lawrence Tim , Hollenhorst Marie A.
Published: December 2019

Despite many years of published medical society guidelines for red blood cell (RBC) transfusion therapy, along with clinical trials that provide Level 1 evidence that restrictive transfusion practices can be used safely and are equivalent to transfusions given more liberally, annualized blood transfusion activity did not begin to decline in the United States until 2010. Adoption of electronic medical records has subsequently allowed implementation of clinical decision support (CDS): best practice alerts that can be initiated to improve the use of blood components. We describe our own institutional experience using a targeted CDS to promote restrictive blood transfusion practice and to improve RBC use. A 42% reduction in RBC transfusions was demonstrated at our institution from a baseline in 2008 through 2015, and the rate remained stable through 2018. Although the data cannot be used to infer causality, this decreased RBC use was accompanied by improved clinical outcomes.
Opportunities for immunotherapy in childhood acute myeloid leukemia
Authors: Lamble Adam J. , Tasian Sarah K.
Published: December 2019

Clinical outcomes for children with acute myeloid leukemia (AML) have improved minimally during the past 4 decades despite maximally intensive chemotherapy, hematopoietic stem cell transplantation, and optimized supportive care. Chemoresistance and relapse remain major sources of childhood cancer–associated mortality and highlight the need for alternative treatment approaches. The remarkable recent success of humoral and cellular immunotherapies in children and adults with relapsed/refractory B-acute lymphoblastic leukemia has inspired hope for similar accomplishments in patients with AML. However, unique challenges exist, including the biologic and immunophenotypic heterogeneity of childhood AML and the significant potential for on-target/off-tumor immunotherapeutic toxicity due to target antigen expression on nonmalignant cells. This article reviews the current landscape of antibody-based and cellular immunotherapies under current clinical evaluation with an emphasis on active or soon-to-open phase 1 trials for children with relapsed/refractory AML.
Cutting-based single atomic layer removal mechanism of monocrystalline copper: edge radius effect
Authors: Xie Wenkun , Fang Fengzhou
Published: December 2019

The ultimate objective of mechanical cutting is to down minimum chip thickness to single atomic layer. In this study, the cutting-based single atomic layer removal mechanism on monocrystalline copper is investigated by a series of molecular dynamics analysis. The research findings report that when cutting depth decreases to atomic scale, minimum chip thickness could be down to single atomic layer by mechanical cutting using rounded edge tool. The material removal behaviour during cutting-based single atomic layer removal exhibits four characteristics, including chip formation by shearing-stress driven dislocation motion, elastic deformation on the processed surface, atomic sizing effect, and cutting-edge radius effect. Based on this understanding, a new cutting model is proposed to study the material removal behaviour in cutting-based single atomic layer removal process, significantly different from those for nanocutting and conventional cutting. The outcomes provide theoretical support for the research and development of the atomic and close-to-atomic scale manufacturing technology.
Variation in species assemblages due to micro-topography and flow regime govern vegetation carbon stock in seasonal floodplain wetlands
Authors: Sarkar Priyanka , Das Tapati , Adhikari Dibyendu
Published: December 2019

Hypothesis

Variation in species assemblages due to micro-topographic features and flow regime determine vegetation carbon stock in floodplain wetlands.

Material and method

We tested this hypothesis in Chatla—a tropical floodplain wetland located in northeast India. Five sampling stations characterized by contrasting micro-topographic and flow parameters were selected in the wetland for study. Species composition, assemblage pattern, and vegetation carbon stock were studied in these stations during three flood phases, i.e., early, middle, and late flood phases following standard methods. Univariate and multivariate statistics were used to determine the relationship between the selected environmental parameters, plant species assemblages, and vegetation carbon stock of the wetland.

Results

Thirty-one species of herbs and five species of shrubs were recorded from the five stations in Chatla floodplain wetland. Flow regime characterized by water flow velocity and discharge showed substantial variations across the stations. These parameters in turn are related to variations in the micro-topographic characteristics namely depth, width, and cross-sectional area of the stations. Plant species composition and abundance differed significantly with respect to micro-topography and flow regime as revealed by the cluster diagram. The canonical correspondence analysis revealed strong association of plant species assemblages with the micro-topography and flow regime within the wetland. Multiple regression analysis revealed a significant positive relationship of the vegetation carbon stock with the water discharge.

Conclusions

Spatial variation in plant species diversity because of micro-topography and flow regime determines the vegetation carbon stock in floodplain wetlands. Modification of these parameters by anthropogenic activities such as mining and quarrying may potentially influence the carbon stocking potential of seasonal floodplain wetlands. Therefore, appropriate measures should be taken to maintain the integrity of the natural topographic features of such wetlands.
Composition of camel milk and evaluation of food supply for camels in Uzbekistan
Authors: Pak Valeriy V. , Khojimatov Olim K. , Abdiniyazova Gulnara J. , Magay Elena B.
Published: December 2019

Background

In Uzbekistan, local people consumed camel milk products since ancient time. Camel milk is a source of energy and nutrients which are consumed as raw or fermented products and also provides various potential health benefits for human.

Methods

The data were collected during 2016–2018 by expeditions in desert and semi-desert regions of Uzbekistan. Three hundred sixty sheets of plants have been collected from those regions. Forty-two samples of raw camel milk were collected at two periods of the year: 21 samples during summer (June, July, and August) and 21 during winter (December, January, and February).

Results and discussion

Analysis of the composition of camel milk samples revealed the particular richness of camel milk in protein and fat content. Average values of protein and fat were found as 4.04 ± 0.36% w/v and 4.89 ± 0.26% w/v, respectively. Analysis of the composition of camel milk showed that protein, fat, and dry matter contents were comparatively lower in the summer period. Also, it was found that the average values of all components decreased from December to February and had a tendency to grow from June to August. This finding suggests a seasonal variation in available food supply. Investigation of an available fodder flora revealed that a fodder base consists of around 300 plants. Analysis of plant species revealed that 30 plants were widely used in traditional medicine.

Conclusion

Our results suggested that the healing benefit of camel milk can be connected with higher content of proteins including the various protective proteins and with secretion of the bioactive compounds from plants with medicinal properties via food.
Modelling and control of solar-driven humidification–dehumidification desalination plant
Authors: Gabra Bahy , Rady Mohamed , Abdel Ghany A. M. , Shamseldin Mohamed. A.
Published: December 2019

This article reports on mathematical modelling and control of a solar-driven humidification–dehumidification desalination plant. Mathematical models for the components are constructed using CARNOT toolbox in MATLAB environment. Model validation has been shown by comparison with published experimental data. Solar collector outlet temperature control is a key parameter to optimize plant performance. In this study, solar field pump flow rate is controlled to maintain the collector outlet temperature at a predetermined set value. Three types of PID controllers are tested. These include PID, nonlinear PID and fractional-order PID. Controllers’ gains are optimized using genetic algorithm technique. The results show that FOPID controller offers a superior dynamic and static performance and can be automatically adjusted to compensate for weather changes.
Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation–Positive Non–Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study
Authors: Yang James C.H. , Kim Sang-We , Kim Dong-Wan , Lee Jong-Seok , Cho Byoung Chul , Ahn Jin-Seok , Lee Dae H. , Kim Tae Min , Goldman Jonathan W. , Natale Ronald B. , Brown Andrew P. , Collins Barbara , Chmielecki Juliann , Vishwanathan Karthick , Mendoza-Naranjo Ariadna , Ahn Myung-Ju
Published: December 2019

PURPOSE

In this phase I study (BLOOM), osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was evaluated in patients with leptomeningeal metastases (LMs) from EGFR-mutated (EGFRm) advanced non–small-cell lung cancer (NSCLC) whose disease had progressed on previous EGFR-TKI therapy.

PATIENTS AND METHODS

Patients with cytologically confirmed LM received osimertinib 160 mg once daily. Objectives were to assess confirmed objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), pharmacokinetics (PK), and safety. Additional efficacy evaluations included changes from baseline in CSF cytology and neurologic examination. Measurable lesions were assessed by investigator according to RECIST version 1.1. LMs were assessed by neuroradiologic blinded central independent review (BICR) according to Response Assessment in Neuro-Oncology LM radiologic criteria and by investigator.

RESULTS

Forty-one patients were enrolled. LM ORR and DoR by neuroradiologic BICR were 62% (95% CI, 45% to 78%) and 15.2 months (95% CI, 7.5 to 17.5 months), respectively. Overall, ORR by investigator was 41% (95% CI, 26% to 58%), and median DoR was 8.3 months (95% CI, 5.6 to 16.5 months). Median investigator-assessed PFS was 8.6 months (95% CI, 5.4 to 13.7 months) with 78% maturity; median OS was 11.0 months (95% CI, 8.0 to 18.0 months) with 68% maturity. CSF tumor cell clearance was confirmed in 11 (28%; 95% CI, 15% to 44%) of 40 patients. Neurologic function was improved in 12 (57%) of 21 patients with an abnormal assessment at baseline. The adverse event and PK profiles were consistent with previous reports for osimertinib.

CONCLUSION

Osimertinib showed meaningful therapeutic efficacy in the CNS and a manageable safety profile at 160 mg once daily in patients with EGFRm NSCLC and LM.