bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk and management of pre-diabetes
Authors: Beulens JWJ , Rutters F , Rydén L , Schnell O , Mellbin L , Hart HE , Vos RC
Published: November 2019

Type 2 diabetes mellitus (T2DM) is associated with a two- to four-fold increased risk of developing cardiovascular disease (CVD) and microvascular complications, which may already be present before diagnosis. It is, therefore, important to detect people with an increased risk of T2DM at an early stage. In order to identify individuals with so-called ‘pre-diabetes’, comprising impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), current guidelines have developed definitions based on fasting plasma glucose, two-hour glucose concentrations and haemoglobin A1c. Subjects with pre-diabetes are at an increased risk of developing T2DM and CVD. This elevated risk seems similar according to the different criteria used to define pre-diabetes. The risk of progression to T2DM or CVD does, however, depend on other risk factors such as sex, body mass index and ethnicity. Based on the risk factors to develop T2DM, many risk assessment models have been developed to identify those at highest risk. These models perform well to identify those at risk and could be used to initiate preventive interventions. Many studies have shown that lifestyle modification and metformin are effective in preventing the development of T2DM, although lifestyle modification seems to have a more sustainable effect. In addition, lifestyle modification seems more effective in those with IGT than those with IFG. In this review, we will describe the different definitions used to define pre-diabetes, progression from pre-diabetes to T2DM or other vascular complications, risk factors associated with progressions and the management of progression to T2DM, ending with clinical recommendations.
Antithrombotic therapy and revascularisation strategies in people with diabetes and coronary artery disease
Authors: Rocca Bianca , Rubboli Andrea , Zaccardi Francesco
Published: November 2019

Background

Diabetes mellitus, largely type 2, affects nearly 10% of the global adult population according to the World Health Organization. Diabetes is an independent risk factor for atherosclerotic cardiovascular diseases, including coronary artery disease. Diabetes patients experience a two to three-fold increased incidence of coronary artery disease, despite improved metabolic control and management of other cardiovascular risk factors.

Discussion

Platelet abnormalities and activation as well as reduced antiplatelet drug responsiveness characterise diabetes mellitus. Mechanisms linking diabetes to platelet and vascular abnormalities, atherogenesis and atherosclerotic cardiovascular disease are still only partially known, highlighting the unique complexity of the pro-atherogenic clinical scenario and its treatment. Consistently, a higher residual cardiovascular risk characterises patients with diabetes compared with those without, in spite of improved antiplatelet and antithrombotic treatment combinations. Randomised clinical trials aimed at optimising antiplatelet treatment specifically in patients with diabetes are lacking, both in acute and chronic coronary artery disease settings. Thus, patients with diabetes are treated with regimens validated in studies including only variable proportions of diabetes patients. Myocardial revascularisation appears to confer a comparable relative benefit between diabetes patients and patients without diabetes, and generally coronary artery bypass grafting has a better outcome in diabetes mellitus versus peripheral coronary intervention. New glucose-lowering drugs have been shown to reduce the incidence of major cardiovascular events in secondary prevention. Type 1 diabetes mellitus remains less explored than type 2 in this context.

Conclusion

Diabetes-tailored antithrombotic strategies in acute and chronic coronary artery disease remain an unmet clinical need, requiring ad-hoc trials and precision pharmacological strategies.
Targets for blood glucose: What have the trials told us
Authors: Valensi Paul , Prévost Gaëtan , Schnell Oliver , Standl Eberhard , Ceriello Antonio
Published: November 2019

The challenges of diabetes treatment are to prevent or delay microangiopathic complications and macrovascular disease. Early, effective and sustained glycaemic control is advocated by all diabetes guidelines to mitigate the risks of prolonged hyperglycaemia. The post-hoc analyses of the large randomised glucose intervention trials and the long-term results of these trials have shown clearly that intensive glycaemic control may have more favourable cardiovascular effects when initiated earlier in the course of diabetes, particularly among in patients without cardiovascular disease. Based on the intervention trials a haemoglobin A1c level of less than 7.0% (<53 mmol/mol) is a generally accepted target to reduce microvascular disease and should be initiated early in the course of the diabetes. However, haemoglobin A1c targets should be individualised. Achieving a good glycaemic control without detrimental effect and preferably with benefit to the cardiovascular system and to renal function is an important challenge. When targeting a tight glycaemic control, avoidance of hypoglycaemia is crucial particularly in patients with coronary artery disease and in patients with heart failure. The cardiovascular outcomes trials performed to test the cardiovascular safety of the new glucose-lowering therapies offer compelling evidence in favour of the role of these drugs for cardiovascular prevention. Thus, both the glycaemic target and the choice of therapies should now be defined on an individual basis.
Controlling the Crown: Legal Efforts to Professionalize Black Hair
Authors: Donahoo Saran , Smith Asia D.
Published: November 2019

Similar to other aspects of life, White cultural norms influence the evaluations and expectations placed on Black women in the workplace. Even though Bo Derek inspired many White women to wear braids after her character in the film 10, the New York District Court sided with American Airlines when Renee Rogers sued her employer for denying her the right to wear similar braids to work. Nearly 40 years later, laws in California and New York City have finally acknowledged this approach as racial discrimination by making it illegal for any public and private entity from discriminating against Black hair. Building off these competing legal interpretations, this article analyzes the discrimination targeted at Black women’s hairstyles, the directions provided by both the New York City Human Rights Law and the Creating a Respectful and Open World for Natural Hair Act, and the relevance that this issue has for Black women across the nation.
Immediate Post-Operative Reconstruction of Calvarial Bone by Cranioplasty Prosthesis in Calvarial Bone Fibrous Dysplasia
Authors: Gajdhar Shaiq , Gajdhar Sajda Khan
Published: November 2019

Objectives:

Immediate post-operative reconstruction of calvarial bone by cranioplasty prosthesis in calvarial bone fibrous dysplasia. An easy and economical method for reconstruction of the defect.

Methods:

Surgical excision of right parietal cranial space occupied lesion was performed followed by fabrication of immediate postoperative period cranioplasty prosthesis by using clear heat polymerized polymethylmethacrylate.

Results:

The cranial defect created during excision of calvarial bone fibrous dysplasia was immediately replaced by cranioplasty prosthesis which was fabricated in the immediate post-operative period using heat polymethylmethacrylate.

Conclusions:

Polymethylmethacrylate is a very reliable thermoplastic material that can be prefabricated or even placed immediately after post-operative period to produce a suitable prosthesis. Polymethylmethacrylate implants have been outmoded by computer-aided design and computer-aided manufacturing and newer 3-dimensional printed implants, but these newer methods are accompanied by higher expenses and timing issues.
Two Unanticipated Pregnancies While on Cystic Fibrosis Gene-Specific Drug Therapy
Authors: Ladores Sigrid , Bray Leigh Ann , Brown Janet
Published: November 2019

Women with cystic fibrosis (CF) desire to become pregnant and accomplish the same life goals as women without CF. The underlying pathology of CF and medications used to treat this genetically transmitted disease can affect women’s reproductive potential. An interview with Ana (pseudonym), who became pregnant twice while taking the medication lumacaftor/ivacaftor (LUMA/IVA), was analyzed using thematic analysis. She described her experiences related to “Fertility and Pregnancy Surrounding LUMA/IVA,” the major theme that emerged from her narrative. While there are anecdotal reports of infants conceived by women on LUMA/IVA and other CF precision medications, pregnancy rates and outcomes are not systematically tracked. Education about risks and benefits of these medications should be provided as part of comprehensive clinical care.
Early in-hospital exposure to statins and outcome after intracerebral haemorrhage – Results from the Virtual International Stroke Trials Archive
Authors: Doerrfuss Jakob I , Abdul-Rahim Azmil H , Siegerink Bob , Nolte Christian H , Lees Kennedy R , Endres Matthias , Kasner Scott E , Scheitz Jan F ,   on behalf of the Virtual International Stroke Trials Archive (VISTA) collaboration
Published: November 2019

Introduction

Recent data suggest that statin use after intracerebral haemorrhage might be beneficial. However, data on the effects of early in-hospital statin exposure are lacking. Therefore, we sought to assess whether (1) early statin exposure during the acute phase after intracerebral haemorrhage and (2) early continuation of prevalent statin use are associated with favourable functional outcome.

Patients and methods

Data were obtained from the Virtual International Stroke Trials Archive. Patients were categorised according to use patterns of statins during this early in-hospital phase (continuation, discontinuation or new initiation of statins). Univariate and multivariable analyses were conducted to explore the association between early statin exposure and functional outcome.

Results

A total of 919 patients were included in the analysis. Early in-hospital statin exposure (n = 89, 9.7%) was associated with better functional outcome (modified Rankin Scale ≤ 3) compared with 790 patients without statin exposure before or early after the event (66% versus 47%, adjusted OR 2.1, 95% confidence interval 1.3–3.6).  Compared with patients without exposure to statins before and early after the event, early continuation of statin therapy (n = 57) was associated with favourable functional outcome (adjusted odds ratio 2.6, 95% confidence interval 1.3–5.2). The association between early continuation of statins and outcome remained robust in sensitivity analyses restricted to patients able to take oral medication within 72 h and one-week survivors.

Discussion

It is possible that part of the observed associations are not due to a protective effect of statins but are confounded by indication bias.

Conclusion

Statin exposure and continuation of prevalent statin therapy early after intracerebral haemorrhage are associated with favourable functional outcome after 90 days.
Film Review
Authors: Kuttaiah Pranav
Published: November 2019

Kaala | Pa. Ranjith, Director | India | 2018

Raees | Rahul Dholakia, Director | India | 2017
Advancing Meta-Analysis With Knowledge-Management Platforms: Using metaBUS in Psychology
Authors: Bosco Frank A. , Field James G. , Larsen Kai R. , Chang Yingyi , Uggerslev Krista L.
Published: November 2019

In this article, we provide a review of research-curation and knowledge-management efforts that may be leveraged to advance research and education in psychological science. After reviewing the approaches and content of other efforts, we focus on the metaBUS project’s platform, the most comprehensive effort to date. The metaBUS platform uses standards-based protocols in combination with human judgment to organize and make readily accessible a database of research findings, currently numbering more than 1 million. It allows users to conduct rudimentary, instant meta-analyses, and capacities for visualization and communication of meta-analytic findings have recently been added. We conclude by discussing challenges, opportunities, and recommendations for expanding the project beyond applied psychology.
Enriching Meta-Analytic Models of Summary Data: A Thought Experiment and Case Study
Authors: McShane Blakeley B. , Böckenholt Ulf
Published: November 2019

Meta-analysis typically involves the analysis of summary data (e.g., means, standard deviations, and sample sizes) from a set of studies via a statistical model that is a special case of a hierarchical (or multilevel) model. Unfortunately, the common summary-data approach to meta-analysis used in psychological research is often employed in settings where the complexity of the data warrants alternative approaches. In this article, we propose a thought experiment that can lead meta-analysts to move away from the common summary-data approach to meta-analysis and toward richer and more appropriate summary-data approaches when the complexity of the data warrants it. Specifically, we propose that it can be extremely fruitful for meta-analysts to act as if they possess the individual-level data from the studies and consider what model specifications they might fit even when they possess only summary data. This thought experiment is justified because (a) the analysis of the individual-level data from the studies via a hierarchical model is considered the “gold standard” for meta-analysis and (b) for a wide variety of cases common in meta-analysis, the summary-data and individual-level-data approaches are, by a principle known as statistical sufficiency, equivalent when the underlying models are appropriately specified. We illustrate the value of our thought experiment via a case study that evolves across five parts that cover a wide variety of data settings common in meta-analysis.
Ether lipid metabolism by AADACL1 regulates platelet function and thrombosis
Authors: Holly Stephen P. , Gera Nidhi , Wang Putianqi , Wilson Alexander , Guan Ziqiang , Lin Ling , Cooley Brian , Alfar Hammodah R. , Patil Ruchi G. , Piatt Raymond , Leisner Tina M. , Bergmeier Wolfgang , Majumder Rinku , Parise Leslie V.
Published: November 2019

Key Points

An AADACL1 ether lipid substrate is phosphorylated in platelets and acts as an endogenous inhibitor of PKC isoforms. AADACL1 inhibition reduces circulating platelet reactivity and modulates thrombosis and hemostasis in vivo.
Imetelstat inhibits growth of megakaryocyte colony-forming units from patients with essential thrombocythemia
Authors: Baerlocher Gabriela M. , Haubitz Monika , Braschler Thomas R. , Brunold Claudio , Burington Bart , Oppliger Leibundgut Elisabeth , Go Ning
Published: November 2019

Key Points

Clinically relevant imetelstat concentrations significantly inhibit CFU-MEG formation from MNCs of ET patients and reduce hTERT expression. However, similar concentrations of imetelstat do not inhibit cytokine-induced CFU-MEG from MNCs of healthy donors.
Opportunities for immunotherapy in childhood acute myeloid leukemia
Authors: Lamble Adam J. , Tasian Sarah K.
Published: November 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.
Silicon application and related changes in soil bacterial community dynamics reduced ginseng black spot incidence in Panax ginseng in a short-term study
Authors: Li Meijia , Wang Qiuxia , Liu Zhengbo , Pan Xiaoxi , Zhang Yayu
Published: November 2019

Background

This study analyzed the effect of silicon (Si) application on the occurrence of ginseng black spot caused by Alternaria panax. We explored the differences in soil physical and chemical factors and microbial community structure following Si application as well as the key factors that affected the occurrence of ginseng black spot in soil. Potted Panax ginseng plants were used to assess the effect of Si treatment on ginseng black spot. Soil physical and chemical properties were comprehensively analyzed. Bacterial communities were analyzed using Illumina HiSeq sequencing targeting the 16S rRNA gene.

Results

After inoculation with A. panax, the morbidity (and morbidity index) of ginseng with and without Si was 52% (46) and 83% (77), respectively. Soil physical and chemical analysis showed that under the ginseng black spot inoculation, bacterial communities were mainly affected by pH and available potassium, followed by ammonium nitrogen and available Si. NMDS and PLS-DA analyses and the heat maps of relative abundance revealed that Si application elevated the resistance of ginseng black spot as regulated by the abundance and diversity of bacterial flora in rhizosphere soils. Heatmap analysis at the genus level revealed that A. panax + Si inoculations significantly increased the soil community abundance of Sandaracinus, Polycyclovorans, Hirschia, Haliangium, Nitrospira, Saccharothrix, Aeromicrobium, Luteimonas, and Rubellimicrobium and led to a bacterial community structure with relative abundances that were significantly similar to that of untreated soil.

Conclusions

Short-term Si application also significantly regulated the structural impact on soil microorganisms caused by ginseng black spot. Our findings indicated that Si applications may possibly be used in the prevention and treatment of ginseng black spot.
Association and impact of hypertension defined using the 2017 AHA/ACC guidelines on the risk of atrial fibrillation in The Atherosclerosis Risk in Communities study
Authors: Rattani Anas , Claxton J’Neka S. , Ali Mohammed K. , Chen Lin Y. , Soliman Elsayed Z. , Alvaro Alonso
Published: November 2019

Background

Hypertension is an established risk factor for the development of atrial fibrillation (AF). We evaluated the association and population impact of hypertension, defined using the new 2017 guidelines, on risk of AF.

Methods

In this analysis, we included 14,915 participants in the Atherosclerosis Risk in Communities study without history of AF. Participants underwent blood pressure measurements at baseline and their antihypertensive medication use was assessed. Incident AF was ascertained from study electrocardiograms, hospital records and death certificates. Cox proportional models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of AF among individuals with hypertension based on the JNC7 and 2017 ACC/AHA guidelines. Poisson models were used to obtain risk ratios and calculate population-attributable fractions (PAFs).

Results

We identified 2891 cases of incident AF during 21.4 years of mean follow-up. Prevalence of hypertension was 34 and 48% under the JNC7 and 2017 ACC/AHA definitions, respectively. HRs (95%CI) of AF in hypertensives versus non-hypertensives were 1.44 (1.32, 1.56) and 1.37 (1.26, 1.48) after multivariable adjustment under the old and new guidelines, respectively. The corresponding PAF (95%CI) using the old and new guidelines were 11% (8, 13%) and 13% (9, 16%), respectively.

Conclusions

Overall, our analysis shows that even though the prevalence of hypertension using the new criteria is 40% higher than with the old criteria, this does not translate into meaningful increases in AF attributable to hypertension. These results suggest that prevention or treatment of hypertension based on the new (versus old) guidelines may have limited impact on AF incidence.
Non-urate transporter 1, non-glucose transporter member 9-related renal hypouricemia and acute renal failure accompanied by hyperbilirubinemia after anaerobic exercise: a case report
Authors: Furuto Yoshitaka , Kawamura Mariko , Namikawa Akio , Takahashi Hiroko , Shibuya Yuko , Mori Takayasu , Sohara Eisei
Published: November 2019

Background

Renal hypouricemia (RHUC) is an inherited heterogenous disorder caused by faulty urate reabsorption transporters in the renal proximal tubular cells. Anaerobic exercise may induce acute kidney injury in individuals with RHUC that is not caused by exertional rhabdomyolysis; it is called acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise (ALPE).

RHUC is the most important risk factor for ALPE. However, the mechanism of onset of ALPE in patients with RHUC has not been elucidated. The currently known genes responsible for RHUC are SLC22A12 and SLC2A9.

Case presentation

A 37-year-old man presented with loin pain after exercising. Despite having a healthy constitution from birth, biochemical examination revealed hypouricemia, with a uric acid (UA) level of < 1 mg/dL consistently at every health check. We detected acute kidney injury, with a creatinine (Cr) level of 4.1 mg/dL, and elevated bilirubin; hence, the patient was hospitalized. Computed tomography revealed no renal calculi, but bilateral renal swelling was noted. Magnetic resonance imaging detected cuneiform lesions, indicating bilateral renal ischemia. Fractional excretion values of sodium and UA were 0.61 and 50.5%, respectively. Urinary microscopy showed lack of tubular injury. The patient’s older sister had hypouricemia. The patient was diagnosed with ALPE. Treatment with bed rest, fluid replacement, and nutrition therapy improved renal function and bilirubin levels, and the patient was discharged on day 5. Approximately 1 month after onset of ALPE, his Cr, UA, and TB levels were 0.98, 0.8, and 0.9 mg/dL, respectively. We suspected familial RHUC due to the hypouricemia and family history and performed genetic testing but did not find the typical genes responsible for RHUC. A full genetic analysis was opposed by the family.

Conclusions

To the best of our knowledge, this is the first report of ALPE with hyperbilirubinemia. Bilirubin levels may become elevated as a result of heme oxygenase-1 activation, occurring in exercise-induced acute kidney injury in patients with RHUC; this phenomenon suggests renal ischemia-reperfusion injury. A new causative gene coding for a urate transporter may exist, and its identification would be useful to clarify the urate transport mechanism.
Digital postpartum hemorrhage management device (DPHMD)
Authors: Tekela Derartu D. , Asmare Abeba G. , Gebremariam Birhan M. , Assegahegn Christian A. , Wami Kidist D. , Nemomssa Hundessa D. , Simegn Gizeaddis L.
Published: November 2019

Background

Primary postpartum hemorrhage (PPH) is an obstetric emergency caused by excessive blood loss that occurs most commonly after the placenta is delivered. PPH can lead to volume depletion, hypovolemic shock, anemia, and it is the leading cause of maternal mortality worldwide. With 470 deaths per 100,000 live births, the maternal mortality ratio in Ethiopia is one of the highest in the world. It is estimated that 94% of births occur at home in Ethiopia and that 10% of maternal deaths are attributed to PPH. Currently, physicians use visual estimation to calculate blood loss and provide fluid during delivery. This traditional method is subjective and generally inaccurate.

Method

In this project, after delivery blood loss measurement system integrated with fluid delivery and vital sign monitoring method is proposed. The collection and measurement system collects blood loss after delivery and measures the amount of blood loss. The management system continuously monitors the mother’s heart rate and blood pressure. These vital sign values are integrated with the measured blood loss to estimate the amount of IV fluid required to be delivered for the mother. The rate of IV fluid delivery is regulated by a flow rate sensor and solenoid valve.

Results

The prototype was built and undergone through different tests and iterations. The proposed device was tested for accuracy, cost effectiveness and ease to use. 91.28% accuracy has been achieved and the prototype was built with less than 210 USD.

Conclusion

The proposed design allows physicians, especially those in low resource setting, to estimate blood loss and deliver fluid accurately. This helps to reduce maternal mortality rate that may occur due to postpartum hemorrhage.
Dose-volume parameters predict radiation pneumonitis after induction chemoradiotherapy followed by surgery for non-small cell lung cancer: a retrospective analysis
Authors: Katsui Kuniaki , Ogata Takeshi , Watanabe Kenta , Katayama Norihisa , Soh Junichi , Kuroda Masahiro , Kiura Katsuyuki , Maeda Yoshinobu , Toyooka Shinichi , Kanazawa Susumu
Published: November 2019

Background

The relationship between lung dose-volume histogram (DVH) parameters and radiation pneumonitis (RP) associated with induction concurrent chemoradiotherapy (CCRT) followed by surgery in patients with non-small cell lung cancer (NSCLC) is unclear, particularly when concerning irradiation of the whole lung prior to resection. We performed this study to identify factors associated with grade ≥ 2 RP in such patients.

Methods

Patients who received induction CCRT (chemotherapy: cisplatin and docetaxel; radiotherapy: 46 Gy/23 fractions) between May 2003 and May 2017 were reviewed. The mean lung dose (MLD) and the percentage of the lung volume that received ≥5 Gy (V5) and ≥ 20 Gy (V20) were calculated. Factors associated with the development of grade ≥ 2 RP were analyzed.

Results

One hundred and eight patients were included in this study, 34 (31.5%) of whom experienced grade ≥ 2 RP. A V20 ≥ 21%, an MLD ≥10 Gy, and a lower lobe tumor location were significant predictors of grade ≥ 2 RP on univariate analysis (p = 0.007, 0.002, and 0.004, respectively). Moreover, an MLD ≥10 Gy and lower lobe location were significant predictors of grade ≥ 2 RP on multivariate analysis (p = 0.026 and 0.0043, respectively). The cumulative incidence rates of grade ≥ 2 RP at 6 months were 15.7 and 45.6% in patients with MLDs < 10 Gy and ≥ 10 Gy, respectively, and were 23.5 and 55.6% in patients with upper/middle lobe- vs. lower lobe-located tumors, respectively.

Conclusions

MLD and lower lobe location were predictors of grade ≥ 2 RP in patients who received induction CCRT. It is necessary to reduce the MLD to the greatest extent possible to prevent the occurrence of this adverse event.
Impact of early chimerism status on clinical outcome in children with acute lymphoblastic leukaemia after haematopoietic stem cell transplantation
Authors: Lejman Monika , Zaucha-Prażmo Agnieszka , Zawitkowska Joanna , Mroczkowska Aleksandra , Grabowski Dominik , Kowalczyk Jerzy R. , Drabko Katarzyna
Published: November 2019

Background

The significance of very early chimerism assessment before day + 28, which is considered the moment of engraftment, is still unclear. In this retrospective study, we evaluated the clinical impact of very early chimerism on the clinical outcome after allogeneic haematopoietic stem cell transplantation (allo-HSCT) in children with acute lymphoblastic leukaemia (ALL).

Methods

The study group included 38 boys and 18 girls. Very early chimerism was evaluated on days + 7, + 14, + 21 and + 28 after the transplant. Short tandem repeat polymerase chain reaction (STR PCR) was used to analyse chimerism.

Results

Overall survival (OS) and event-free survival (EFS) were 84 and 80%, respectively. The OS in the group of 24 patients with complete donor chimerism on day + 14 was 83%, and it did not differ statistically compared to the 32 patients with mixed chimerism on day + 14 (OS was 84%). In our cohort of patients, the matched unrelated donor, male gender of donor, number of transplanted cells above 4.47 × 106 kg and no serotherapy with anti-thymocyte globulin (ATG) were statistically related to a higher level of donor chimerism. The immunophenotypes of disease, age of patient at time HSCT, recipient sex, stem cell source (peripheral blood/bone marrow) and conditioning regimen had no impact on early chimerism. Acute graft versus host disease grades II-IV was diagnosed in 23 patients who presented with donor chimerism levels above 60% on day 7.

Conclusions

The data presented in this study provide valuable insight into the analysis of very early chimerism in children with ALL treated with HSCT.
Intravitreal anti-VEGF treatment for choroidal neovascularization secondary to traumatic choroidal rupture
Authors: Barth T. , Zeman F. , Helbig H. , Gamulescu M.-A.
Published: November 2019

Background

So far only single cases with short follow-up have been reported on the use of intravitreal anti-VEGF for traumatic choroidal neovascularizations (CNV). This paper reports a large case series of patients with CNV secondary to choroidal rupture after ocular trauma receiving intravitreal anti-VEGF (vascular endothelial growth factor) injections.

Methods

Fifty-four patients with unilateral choroidal rupture after ocular trauma diagnosed between 2000 and 2016 were retrospectively evaluated. Eleven patients with CNV secondary to choroidal rupture were identified. Five eyes with traumatic secondary CNV were treated with anti-VEGF and were systematically analysed. The other 4 patients with inactive CNV underwent watchful observation.

Results

Four men and one woman with a mean age of 29 years (SD 12.4; range 19–45) had intravitreal anti-VEGF therapy for traumatic CNV. Another 4 patients with a mean age of 37 years (SD 6.6; range 31–46) presented with inactive CNV and did not receive specific treatment. In all 9 cases the mean interval between the ocular trauma and the diagnosis of CNV was 5.7 months (SD 4.75; range 2–12). In the treatment group per eye 4.2 injections (SD 3.2; range 1–8) were given on average. Four eyes were treated with bevacizumab and one eye with ranibizumab. Regression of CNV was noted in all eyes. In 4 eyes visual acuity (VA) improved, one eye kept stable visual acuity.

Conclusions

Here, we present the up to now largest case series of traumatic CNV membranes treated with anti-VEGF injections with a mean follow-up period of 5 years. Intravitreal anti-VEGF therapy seems to be safe and effective for secondary CNV after choroidal rupture. Compared to exudative age-related macular degeneration fewer injections are needed to control the disease.

Trial registration

Retrospective registration with local ethics committee on 21 March 2019. Trial registration number is 19-1368-104.
Long term outcomes from lymphatic venous anastomosis after total hysterectomy to prevent postoperative lymphedema in lower limb
Authors: Ezawa Masahiro , Sasaki Hiroshi , Yamada Kyosuke , Takano Hirokuni , Iwasaka Tsuyoshi , Nakao Yoshifumi , Yokochi Tomoki , Okamoto Aikou
Published: November 2019

Background

Lymphedema in lower limb is one of major postoperative complications followed by a total hysterectomy with lymph node dissection. The objective of this report is to examine a long-term result of lymphaticovenous anastomosis procedure as a preventive surgery.

Methods

Sixteen patients with endometrial cancer underwent an abdominal hysterectomy with a bilateral salpingo-oophorectomy. Just after pelvic lymph node dissection, either end-to-end or sleeve anastomosis utilizing venules and suprainguinal lymph vessels was performed. During the observation period from 4 to 13 years, the symptom of lymphedema in lower extremities has been assessed.

Results

Among 16 patients, 1 presented postoperative lymphedema grade 3 (CTCAE (Common Terminology Criteria for Adverse Events) Ver. 4.0, 10025233) in lower limb, and a second surgery at 7 years after the first one was required. Other 6 patients showed non-severe symptoms of lymphedema, diagnosed as grade 1. The rest 9 patients did not show any symptoms of postoperative lymphedema in a long term (up to 13 years).

Conclusion

From the long term outcomes of our 16 cases, we propose that a direct lymphaticovenous microsurgery immediately after a hysterectomy with lymphadenectomy of external inguinal lymph node is one of the appropriate therapeutic choices to prevent severe lymphedema in lower limb.
The role of the adipocytokines vaspin and visfatin in vascular endothelial function and insulin resistance in obese children
Authors: Yin Chunyan , Hu Wei , Wang Ming , Xiao Yanfeng
Published: November 2019

Background

We measured the concentrations of the adipocytokines vaspin and visfatin in obese Chinese children. Furthermore, we studied the correlation of these adipocytokines with early-onset metabolic and vascular sequelae among these children.

Methods

A total of 244 children (160 obese and 84 lean) were included in this study. Vaspin and visfatin were detected using enzyme-linked immunosorbent assays. We also assayed other metabolic and cardiovascular parameters. The associations of serum vaspin and visfatin concentrations with metabolic and cardiovascular parameters were determined.

Results

We found a significant elevation in the concentrations of vaspin and visfatin in obese children compared to the concentrations in lean children. Additionally, we found a significant positive correlation between visfatin and vaspin levels, as well as inflammatory cell infiltration and markers of endothelial activation, but these factors did not affect insulin resistance in obese children. Multiple regression analyses confirmed that vaspin is the strongest predictor of higher tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), angiotensin-2 (Ang-2), vascular cellular adhesion molecule-1 (VCAM-1), and E-selectin levels. We also found a significant association between visfatin and Ang-2, IL-6, VCAM-1, and E-selectin levels.

Conclusion

The adipocytokines vaspin and visfatin are significantly interrelated, and both adipocytokines play a role in vascular endothelial function and inflammation.
Manifestations of verbal and physical violence towards doctors: a comparison between hospital and community doctors
Authors: Nevo Tamar , Peleg Roni , Kaplan Daniel M. , Freud Tamar
Published: November 2019

Background

Healthcare workers, in the hospital and in community clinics, are frequently exposed to verbal and physical abuse that can lead to frustration and despair. This study’s objectives were to evaluate trends in violence towards hospital and community doctors in the Negev region of Israel and to compare them to the results of a previous 2005 study.

Methods

A convenience sample of doctors in the hospital and in the community completed anonymous questionnaires on previous exposure to work place violence and their attitudes to it. The data were collected in 2017.

Results

One hundred forty-five doctors participated in the study, of who 63 were hospital doctors and 82 were community doctors. Fifty nine percent of the doctors reported that they experienced at least one incident of verbal abuse over the previous year and 9% were exposed to physical abuse, compared to 56 and 9%, respectively, in the previous study. More hospital doctors (58.7%) were exposed to verbal abuse on the part of family members than community doctors (35.8%) (P = 0.007). The most common reason for a violent outbreak was long waiting times, followed by dissatisfaction with treatment, both consistent with the findings in the previous study. Seventy one percent said that violence was a major problem for doctors. The majority (73.9%) had not participated in a workshop or other training for preventing workplace violence or coping with it, an improvement over the 83% who reported not receiving any training in the previous study.

Conclusions

Workplace violence is a major issue, which affects hospital and community physicians alike. There is a rise in the number of doctors who have undergone training in this area, although the majority have yet to receive formal training.
Type I interferon (IFN)-inducible Absent in Melanoma 2 proteins in neuroinflammation: implications for Alzheimer’s disease
Authors: Choubey Divaker
Published: November 2019

Cumulative evidence indicates that activation of innate immune responses in the central nervous system (CNS) induces the expression of type 1 interferons (T1 IFNs), a family of cytokines. The T1 IFNs (IFN-α/β), through activation of the JAK/STAT-signaling in microglia, astrocytes, and neurons, induce the expression of IFN-inducible proteins, which mediate the pro- and anti-inflammatory functions of IFNs. Accordingly, T1 IFN-inducible Absent in Melanoma 2 proteins (murine Aim2 and human AIM2) negatively regulate the expression of TI IFNs and, upon sensing higher levels of cytosolic DNA, assemble the Aim2/AIM2 inflammasome, resulting in activation of caspase-1, pyroptosis, and the secretion of pro-inflammatory cytokines (e.g., IL-1β and IL-18). Of interest, studies have indicated a role for the Aim2/AIM2 proteins in neuroinflammation and neurodegenerative diseases, including Alzheimer’s disease (AD). The ability of Aim2/AIM2 proteins to exert pro- and anti-inflammatory effects in CNS may depend upon age, sex hormones, cell-types, and the expression of species-specific negative regulators of the Aim2/AIM2 inflammasome. Therefore, we discuss the role of Aim2/AIM2 proteins in the development of AD. An improved understanding of the role of Absent in Melanoma 2 proteins in AD could identify new approaches to treat patients.
Downregulation of microRNA-30a-5p contributes to the replication of duck enteritis virus by regulating Beclin-1-mediated autophagy
Authors: Wu Xianglong , Jia Renyong , Wang Mingshu , Chen Shun , Liu Mafeng , Zhu Dekang , Zhao Xinxin , Yang Qiao , Wu Ying , Yin Zhongqiong , Zhang Shaqiu , Huang Juan , Zhang Ling , Liu Yunya , Yu Yanling , Pan Leichang , Tian Bin , Rehman Mujeeb Ur , Chen Xiaoyue , Cheng Anchun
Published: November 2019

Background

MicroRNAs (miRNAs) is increasingly recognized as an important element in regulating virus-host interactions. Our previous results showed that cellular miR-30a-5p was significantly downregulated after duck enteritis virus (DEV) infection cell. However, whehter or not the miR-30a-5p is involved in DEV infection has not been known.

Methods

Quantitative reverse-transcription PCR (qRT-PCR) was used to measure the expression levels of miRNAs(miR-30a-5p) and Beclin-1 mRNA. The miR-30a-5p - Beclin-1 target interactions were determined by Dual luciferase reporter assay (DLRA). Western blotting was utilized to analyze Beclin-1-mediated duck embryo fibroblast (DEF) cells autophagy activity. DEV titers were estimated by the median tissue culture infective dose (TCID50).

Results

The miR-30a-5p was significantly downregulated and the Beclin-1 mRNA was significantly upregulated in DEV-infected DEF cells. DLRA confirmed that miR-30a-5p directly targeted the 3′- UTR of the Beclin-1 gene. Overexpression of miR-30a-5p significantly reduced the expression level of Beclin-1protein (p < 0.05), leading to the decrease of Beclin-1-mediated autophagy activity, which ultimately suppressed DEV replication (P < 0.05). Whereas transfection of miR-30a-5p inhibitor increased Beclin-1-mediated autophagy and triggered DEV replication during the whole process of DEV infection (P < 0.01).

Conclusions

This study shows that miR-30a-5p can inhibit DEV replication through reducing autophagy by targeting Beclin-1. These findings suggest a new insight into virus-host interaction during DEV infection and provide a potential new antiviral therapeutic strategy against DEV infection.
High-throughput long paired-end sequencing of a Fosmid library by PacBio
Authors: Dai Zhaozhao , Li Tong , Li Jiadong , Han Zhifei , Pan Yonglong , Tang Sha , Diao Xianmin , Luo Meizhong
Published: November 2019

Background

Large insert paired-end sequencing technologies are important tools for assembling genomes, delineating associated breakpoints and detecting structural rearrangements. To facilitate the comprehensive detection of inter- and intra-chromosomal structural rearrangements or variants (SVs) and complex genome assembly with long repeats and segmental duplications, we developed a new method based on single-molecule real-time synthesis sequencing technology for generating long paired-end sequences of large insert DNA libraries.

Results

A Fosmid vector, pHZAUFOS3, was developed with the following new features: (1) two 18-bp non-palindromic I-SceI sites flank the cloning site, and another two sites are present in the skeleton of the vector, allowing long DNA inserts (and the long paired-ends in this paper) to be recovered as single fragments and the vector (~ 8 kb) to be fragmented into 2–3 kb fragments by I-SceI digestion and therefore was effectively removed from the long paired-ends (5–10 kb); (2) the chloramphenicol (Cm) resistance gene and replicon (oriV), necessary for colony growth, are located near the two sides of the cloning site, helping to increase the proportion of the paired-end fragments to single-end fragments in the paired-end libraries. Paired-end libraries were constructed by ligating the size-selected, mechanically sheared pooled Fosmid DNA fragments to the Ampicillin (Amp) resistance gene fragment and screening the colonies with Cm and Amp. We tested this method on yeast and Setaria italica Yugu1. Fosmid-size paired-ends with an average length longer than 2 kb for each end were generated. The N50 scaffold lengths of the de novo assemblies of the yeast and S. italica Yugu1 genomes were significantly improved. Five large and five small structural rearrangements or assembly errors spanning tens of bp to tens of kb were identified in S. italica Yugu1 including deletions, inversions, duplications and translocations.

Conclusions

We developed a new method for long paired-end sequencing of large insert libraries, which can efficiently improve the quality of de novo genome assembly and identify large and small structural rearrangements or assembly errors.
Clinical outcomes of treatment with locking compression plates for distal femoral fractures in a retrospective cohort
Authors: Kiyono Masahiro , Noda Tomoyuki , Nagano Hiroshi , Maehara Takashi , Yamakawa Yasuaki , Mochizuki Yusuke , Uchino Takahiko , Yokoo Suguru , Demiya Koji , Saiga Kenta , Shimamura Yasunori , Ozaki Toshifumi
Published: November 2019

Background

Plate fixation is one of the standard surgical treatments for distal femoral fractures. There are few reports on the relationship between the screw position and bone union when fixing by the bridging plate (relative stability) method.

Methods

This retrospective study included 71 distal femoral fractures of 70 patients who were treated with the locking compression plate for distal femur (DePuy Synthes Co., Ltd, New Brunswick, CA, USA). The following measurements were evaluated and analyzed: (1) bone union rate, (2) bridge span length (distance between screws across the fracture), (3) plate span ratio (plate length/bone fracture length), (4) number of empty holes (number of screw holes not inserted around the fracture), and (5) medial fracture distance (bone fracture distance on the medial side of the distal femur). Patient demographics (age), comorbidities (smoking, diabetes, chronic steroid use, dialysis), and injury characteristics (AO type, open fracture, infection) were obtained for all participants. Univariate analysis was performed on them.

Results

Of 71 fractures, 26 fractures were simple fractures, 45 fractures were comminuted fractures, and 7 fractures resulted in non-union. Non-union rate was significantly higher in comminuted fractures with bone medial fracture distance exceeding 5 mm.

Non-union was founded in simple fractures with bone medial fracture distance exceeding 2 mm, but not significant (p= 0.06). In cases with simple fractures, one non-union case had one empty hole and one non-union case had four empty holes, whereas in cases with comminuted fractures, five non-union cases had two more empty holes.

Conclusions

We concluded that bone fragment distance between fracture fragments is more important than bridge span length of the fracture site and the number of empty holes. Smoking and medial fracture distance are prognostic risk factors of nonunion in distal femoral fractures treated with LCP as bridging plate.
Lamotrigine-induced hemophagocytic lymphohistiocytosis with Takotsubo cardiomyopathy: a case report
Authors: Zhou Jenny Y. , Martinez Jordan A. , Shen John Paul
Published: November 2019

Background

Hemophagocytic lymphohistiocytosis is a rare hematological syndrome characterized by excessive and uncontrolled activation of the immune system. The often nonspecific nature of early symptoms and the potential for progression to multiorgan failure and death if appropriate therapy is not started promptly, highlight the importance of heightened recognition for this uncommon disease. Although there are well-described associations of hemophagocytic lymphohistiocytosis with infectious, malignant, and autoimmune diseases and an established treatment protocol for these cases, the link between medications and hemophagocytic lymphohistiocytosis is less clearly established and the optimal treatment of these cases less well defined.

Case presentation

Here we describe the case of a 45-year-old caucasian woman presenting with signs and symptoms consistent with hemophagocytic lymphohistiocytosis, induced by recent exposure to lamotrigine. She had a rapidly progressive clinical course, complicated by multiorgan failure including stress-induced Takotsubo cardiomyopathy and cardiac arrest. With dexamethasone and etoposide therapy, she made a full and sustained recovery.

Conclusions

This case highlights that medication-induced hemophagocytic lymphohistiocytosis appears to respond similarly to the same dexamethasone and etoposide treatment regimen developed for other non-drug-induced forms of hemophagocytic lymphohistiocytosis. With the continued cessation of the offending agent there has not been need for maintenance therapy and no relapse to date. In addition, given the risk for cardiomyopathy, a clinical complication not classically associated with hemophagocytic lymphohistiocytosis, echocardiogram and telemetry monitoring should be considered in the initial workup of suspected hemophagocytic lymphohistiocytosis.
Building an Otoscopic screening prototype tool using deep learning
Authors: Livingstone Devon , Talai Aron S. , Chau Justin , Forkert Nils D.
Published: November 2019

Background

Otologic diseases are often difficult to diagnose accurately for primary care providers. Deep learning methods have been applied with great success in many areas of medicine, often outperforming well trained human observers. The aim of this work was to develop and evaluate an automatic software prototype to identify otologic abnormalities using a deep convolutional neural network.

Material and methods

A database of 734 unique otoscopic images of various ear pathologies, including 63 cerumen impactions, 120 tympanostomy tubes, and 346 normal tympanic membranes were acquired. 80% of the images were used for the training of a convolutional neural network and the remaining 20% were used for algorithm validation. Image augmentation was employed on the training dataset to increase the number of training images. The general network architecture consisted of three convolutional layers plus batch normalization and dropout layers to avoid over fitting.

Results

The validation based on 45 datasets not used for model training revealed that the proposed deep convolutional neural network is capable of identifying and differentiating between normal tympanic membranes, tympanostomy tubes, and cerumen impactions with an overall accuracy of 84.4%.

Conclusion

Our study shows that deep convolutional neural networks hold immense potential as a diagnostic adjunct for otologic disease management.