bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropilin‐1 maintains dimethylarginine dimethylaminohydrolase 1 expression in endothelial cells, and contributes to protection from angiotensin II–induced hypertension
Authors: Wang Ying , Wang Enfeng , Zhang Yuebo , Madamsetty Vijay S. , Ji Baoan , Radisky Derek C. , Grande Joseph P. , Misra Sanjay , Mukhopadhyay Debabrata 
Published: August 2018

ABSTRACTDimethylarginine dimethylaminohydrolases (DDAHs) are known to degrade asymmetric dimethylarginine, an endogenous inhibitor of NOS, and maintain vascular homeostasis; however, the regulatory pathways of DDAHs remain unclear. In this study, we aimed to define the role of transmembrane glycoprotein neuropilin‐1 (NRP1) in the expression of DDAHs and investigate the potential roles of NRP1 in regulation of blood pressure. Short hairpin RNA–mediated knockdown of NRP1 reduced the level and mRNA stability of DDAH1 but not DDAH2 in HUVECs, whereas overexpression of NRP1 increased the mRNA stability of DDAH1. Meanwhile, mesenteric arteries and lung vascular endothelial cells of tamoxifen‐inducible endothelial cell–specific NRP1 knockout mice exhibited decreased expression of DDAH1 and slightly increased expression of DDAH2. Mechanistically, the regulation of NRP1 on DDAH1 expression is mediated by a posttranscriptional mechanism involving miR‐219‐5p in HUVECs. Although the endothelial cell–specific NRP1 knockout mice did not exhibit any significant change in blood pressure at the basal level, they were more sensitive to low‐dose angiotensin II infusion–induced increases in blood pressure. Our results show that NRP1 is required for full expression of DDAH1 in endothelial cells and that NRP1 contributes to protection from low‐dose angiotensin II–induced increases in blood pressure.—Wang, Y., Wang, E., Zhang, Y., Madamsetty, V. S., Ji, B., Radisky, D. C., Grande, J. P., Misra, S., Mukhopadhyay, D. Neuropilin‐1 maintains dimethylarginine dimethylaminohydrolase 1 expression in endothelial cells, and contributes to protection from angiotensin II–induced hypertension. FASEB J. 33, 494–500 (2019). www.fasebj.org
Allogeneic hematopoietic stem-cell transplantation from haploidentical donors using ‘ex-vivo’ T-cell depletion in pediatric patients with hematological malignancies: state of the art review
Authors: González-Vicent Marta , Díaz Perez Miguel A. 
Published: August 2018

Purpose of review
Nowadays, T-cell-depleted haploidentical transplantation is considered a valid approach for children lacking a human leukocyte antigen (HLA) identical donor for allogeneic transplantation. This kind of allogeneic transplant is now widely used especially for pediatric patients with high-risk hematological malignancies. However, relapsing disease and life-threatening viral infections are still relevant clinical problems as a consequence of delayed immune reconstitution. Adoptive cell therapies have been proposed to overcome this problem.

Recent findings
After initial clinical approach using CD34+ selection as method for T-cell depletion (TCD), it was observed that immune reconstitution was delayed and it resulted on high incidence of opportunistic infections and nonrelapse mortality. It is now evident that development over time of graft manipulation techniques for TCD, have provide clinicians a useful tool for overcoming transplant complication such as graft failure, severe graft-vs.-host disease and opportunistic infections. As such, several procedures of almost total or partial TCD have been developed including CD3/CD19 depletion, T cell receptor αβ/CD19 depletion and more recently CD45RA+ depletion. Recent studies showed that immune reconstitution is associated with transplant outcomes. Based on this, haploidentical transplantation is now been explored as platform for cellular therapy to prevent disease recurrence or to treat clinical complications.

Summary
Allogeneic transplantation still remains a standard of care for pediatric patients with high-risk hematological malignancies. In absence of an HLA identical donor, T-cell-depleted haploidentical transplant is now considered a valid option and provide a platform for cellular therapy to prevent relapse disease or to treat opportunistic infections.
Estimating Sizes of Key Populations at the National Level: Considerations for Study Design and Analysis
Authors: Edwards Jessie K. , Hileman Sarah , Donastorg Yeycy , Zadrozny Sabrina , Baral Stefan , Hargreaves James R. , Fearon Elizabeth , Zhao Jinkou , Datta Abhirup , Weir Sharon S. 
Published: August 2018

Background:National estimates of the sizes of key populations, including female sex workers, men who have sex with men, and transgender women are critical to inform national and international responses to the HIV pandemic. However, epidemiologic studies typically provide size estimates for only limited high priority geographic areas. This article illustrates a two-stage approach to obtain a national key population size estimate in the Dominican Republic using available estimates and publicly available contextual information.Methods:Available estimates of key population size in priority areas were augmented with targeted additional data collection in other areas. To combine information from data collected at each stage, we used statistical methods for handling missing data, including inverse probability weights, multiple imputation, and augmented inverse probability weights.Results:Using the augmented inverse probability weighting approach, which provides some protection against parametric model misspecification, we estimated that 3.7% (95% CI = 2.9, 4.7) of the total population of women in the Dominican Republic between the ages of 15 and 49 years were engaged in sex work, 1.2% (95% CI = 1.1, 1.3) of men aged 15–49 had sex with other men, and 0.19% (95% CI = 0.17, 0.21) of people assigned the male sex at birth were transgender.Conclusions:Viewing the size estimation of key populations as a missing data problem provides a framework for articulating and evaluating the assumptions necessary to obtain a national size estimate. In addition, this paradigm allows use of methods for missing data familiar to epidemiologists.
Autologous Fat Transfer as a Treatment for Peripheral Neuropathic Pain without Apparent Cause
Authors: Beugels Jip , Hommes Juliette E. , Balthasar Andrea J.R. , van der Hulst René R.W.J. , Piatkowski de Grzymala Andrzej A. 
Published: August 2018

Summary:
Neuropathic pain has a far-reaching effect on the daily lives of patients. Recently, autologous fat transfer (AFT) has demonstrated promising results in patients with painful scars or after neuroma excision. However, there is a subgroup of patients who do not show any apparent cause for the pain. We hypothesized that in these patients, AFT alone in the area around the affected nerve might lead to beneficial results. Patients with clearly demarcated neuropathic pain and who had exhausted all other treatment options were referred by a pain specialist. Fourteen patients who met the inclusion criteria received AFT in the area of the affected nerve. Pain scored on the visual analog scale, patient satisfaction, and quality of sleep were recorded before and after surgery. To investigate long-term effects, a second follow-up was planned at least 1 year later. Patient satisfaction was 93% after the first follow-up and 86% after more than 1 year. The mean VAS score was 7.4 before surgery and significantly decreased to 3.8 after autologous fat grafting (P < 0.0001) and 4.3 (P = 0.0017) at long-term follow-up. The quality of sleep improved in 50% of the patients, whereas the remainder indicated no difference. No complications were registered. The results show that AFT alone, even over a longer period of time and in patients refractory to multiple treatment modalities, can be useful to treat peripheral neuropathic pain without apparent cause. For definitive evidence, a larger prospective study is warranted.
Preoperative Staging by EBUS in cN0/N1 Lung Cancer
Authors: Leong Tracy L. , Loveland Paula M. , Gorelik Alexandra , Irving Louis , Steinfort Daniel P. 
Published: August 2018

Background:
Performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for staging the radiologically normal mediastinum has been reported with inconsistent findings. We assessed the sensitivity of systematic staging using EBUS-TBNA for detection of radiologically occult mediastinal metastases in cN0/N1 lung cancer.

Methods:
Studies evaluating EBUS-TBNA for systematic mediastinal staging in cN0/N1 lung cancer were identified by systematic review. Data extracted included: participant age and sex; EBUS-TBNA protocol; stage determined by radiology, EBUS-TBNA and surgery; 2×2 tables. Primary outcome was diagnostic accuracy of EBUS-TBNA for detection of unsuspected N2/N3 disease.

Results:
We identified 1173 articles. In total, 13 were included in a qualitative review and 9 (1146 patients) in a quantitative meta-analysis. Mean prevalence of N2/N3 disease was 15% (6% to 24%). EBUS-TBNA had pooled sensitivity of 49% [95% confidence interval (CI), 41%-57%], pooled specificity of 100% (95% CI, 99%-100%), mean negative predictive value 91% (82% to 100%) for detection of unsuspected N2/N3 metastases. Number needed to test to detect occult N2/N3 disease was 14 (95% CI, 10.8-16.3), which halved with addition of per-esophageal endoscopic ultrasound.

Conclusion:
Preoperative systematic staging by EBUS-TBNA of early lung cancer can reduce postoperative upstaging. Sensitivity for detection of radiologically occult mediastinal metastases seems lower than selective sampling of pathologic lymph nodes. Verification of negative results by mediastinoscopy in selected cases remains of value.
Do we need biomarkers for the follow-up and shortening of antibiotic treatment duration?
Authors: Dianti Milagros , Luna Carlos M. 
Published: August 2018

Purpose of review
Clinical and laboratory parameters are useful tools for the diagnosis, follow-up and evaluation of resolution, and to predict outcomes when measured at different time-points onset and serially during follow-up in patients with hospital-acquired pneumonia and/or ventilator-associated pneumonia (HAP/VAP).

Recent findings
Both, the 2017 ERS/ESICM/ESCMID/Asociación Latino Americana de Tórax (EEEAG) and the 2016 IDSA/ATS guidelines (IAG) for the management of HAP/VAP recommend using clinical criteria alone, rather than biomarkers for diagnosis. Several studies were conducted to assess the value of serum biomarker concentration and kinetics for predicting the outcome in HAP/VAP, including C-reactive protein and procalcitonin (PCT). Although the EEEAG do not recommend routinely performing biomarker determinations in addition to bedside clinical assessment in patients receiving antibiotic treatment for VAP or HAP to predict adverse outcomes and clinical response, the IAG recommend that routine bedside clinical assessment should be accompanied by measurements of PCT to guide antimicrobial therapy. Additionally, the 2016 Surviving Sepsis Campaign also suggests that PCT levels can be used to support the shortening of antibiotic therapy.

Summary
Current evidence indicate that there is no recommendation to use biomarkers systematically to guide every decision. However, in some circumstances they might add some relevant information to our everyday practice.
The Iceberg Map of germline mutations in childhood cancer: focus on primary immunodeficiencies
Authors: Kindler Oliver , Quehenberger Franz , Benesch Martin , Seidel Markus G. 
Published: August 2018

Purpose of review
The risk of cancer is higher, and its outcome is worse in patients with primary immunodeficiency (PID) than in members of the general population. Thus, the inter-relationship of malignant diseases with PIDs requires more study.

Recent findings
Large genetic screens identified a vast number of germline mutations in childhood cancer patient samples. Although TP53 was the most frequent single gene identified as mutated, many PID disorders like DNA repair defects are among the inborn causes of childhood cancer. We provide a comprehensive analysis of compiled data from seven recent studies that focused on germline genetic landscapes and preexisting conditions in pediatric oncology. As potentially causal germline variants were identified in ≈8% of malignancies in children and adolescents, we visualized this proportion as the ‘tips of the icebergs’. The results of additional network analyses showed the shared patterns of germline mutations in various malignancies and yielded a spatial distribution of the ‘icebergs’.

Summary
The ‘iceberg map of germline mutations in childhood cancers’ was created to increase the awareness of the inborn genetic underpinnings of childhood malignancies and their relationships with immunodeficiencies. Needs and perspectives of clinical immunologists and pediatric oncologists to both improve patient care and guide research at this critical interface are discussed.

Video Abstract

http://links.lww.com/MOP/A32
A Tale of Confusion From Overlapping Confidence Intervals
Authors: Mittal Nimish , Bhandari Mohit , Kumbhare Dinesh 
Published: August 2018

Abstract
In clinical research presentations, study results are commonly reported in the form of P values and confidence intervals as an estimate of association and treatment effect. The interpretation of confidence intervals that overlap can be confusing and difficult for the reader to draw clinically meaningful conclusions. In this brief report, we describe the basics of confidence intervals and present an example from a recently published randomized control trial to illustrate a common confusion that overlapping confidence intervals between the means of two independent groups may not necessarily reject the true significant difference of effect. It is recommended that investigators use the direct difference of means between groups for confidence interval estimation to reduce type II errors. Clinicians should interpret overlapping confidence intervals with caution and avoid the assumption that overlapping confidence intervals always implies a lack of difference of treatment effect to decide application of treatment.
Integrated Rehabilitation for Breast Cancer Survivors
Authors: Cheville Andrea L. , McLaughlin Sarah A. , Haddad Tufia C. , Lyons Kathleen D. , Newman Robin , Ruddy Kathryn J. 
Published: August 2018

Abstract
The physical and psychological side effects of breast cancer therapies can have substantial impact on survivors' physical and social functioning. Roughly half of the more than 3 million Americans alive with a history of breast cancer report adverse, function-degrading sequelae related to their oncologic treatments. Care delivery models for the timely delivery of rehabilitation services have been proposed yet limitedly vetted or implemented. These include the prospective surveillance model, procedure-linked referrals, survivorship care plans, and risk stratification. Patients' capacity to engage in the rehabilitative process varies during cancer therapy and into survivorship. Perioperative attention generally focuses on managing premorbid impairments and normalizing shoulder function. In contrast, during chemotherapy and radiation therapy, symptom control, constructive coping, and role preservation may become more salient. Risk-stratified, individualized screening and prevention activities for specific impairments have become increasingly feasible through predictive models and analytics. Impairments' severity deleterious impact can be mitigated, as has been established for lymphedema, shoulder dysfunction, chemotherapy-induced peripheral neuropathy, cognitive dysfunction, fatigue, and sexual side effects. Integrated rehabilitative programs, often initiated after the completion of cancer treatment, are available in some countries outside of the United States and may offer survivors vital vocation- and avocation-directed services.
Combinations of Bevacizumab With Cancer Immunotherapy
Authors: Chen Daniel S. , Hurwitz Herbert 
Published: August 2018

AbstractCancer immunotherapy (CIT) has transformed cancer treatment. In particular, immunotherapies targeting the programmed death ligand 1 (PD-L1)/programmed death 1 pathway have demonstrated durable clinical benefit in some patients. However, CIT combinations may create a more favorable environment in which to maximize the potential of the immune system to eliminate cancer. Here we describe 3 key mechanisms related to vascular endothelial growth factor (VEGF)–mediated immunosuppression: inhibition of dendritic cell maturation, reduction of T-cell tumor infiltration, and promotion of inhibitory cells in the tumor microenvironment; supporting data are also described. In addition, we discuss immunomodulatory properties observed within tumors following bevacizumab treatment. Combining anti–PD-L1 and anti-VEGF therapies has shown synergy and positive outcomes in phases I to III studies, particularly in settings where high VEGF levels are known to play an important role in tumor growth. We also review data from key studies supporting combination of bevacizumab and CIT, with a focus on PD-L1/programmed death 1 inhibitors.
Antiangiogenic Therapy in Colorectal Cancer
Authors: Mody Kabir , Baldeo Candice , Bekaii-Saab Tanios 
Published: August 2018

Abstract
Colorectal carcinoma is the third most common cancer worldwide. Approximately 20% of patients with colorectal cancer will have metastatic disease at the time of initial diagnosis, and approximately 30% to 50% of patients with primary colon cancer will relapse and die of metastatic cancer. The 5-year survival rate of metastatic colorectal cancer remains disappointing at approximately 10%.
Angiogenesis plays a significant role in tumor growth and metastasis in colorectal carcinoma. There are currently 4 US Food and Drug Administration–approved antiangiogenic agents for metastatic colorectal cancer. Bevacizumab is the only antiangiogenic agent approved by the US Food and Drug Administration for first-line treatment of metastatic colorectal cancer. Other antiangiogenic agents include ramucirumab, ziv-aflibercept, and regorafenib. We review the data supporting the use of antiangiogenics in this disease.
Clinical management of cystic echinococcosis: state of the art and perspectives
Authors: Stojković Marija , Weber Tim F. , Junghanss Thomas 
Published: August 2018

Purpose of review
This review draws attention to patients with cystic echinococcosis migrating from highly endemic to non-endemic countries with limited experience in cystic echinococcosis management, to ultrasound-based cyst staging, and to the WHO cyst classification as a powerful, to date underused tool to triage patients into the four currently available treatment modalities.

Recent findings
In non- and low-prevalence countries, cystic echinococcosis is often misclassified. Differential diagnoses, such as simple cysts and other benign and malignant space-occupying lesions, have similar appearances on imaging. Serology is confirmatory but often disappointing due to sensitivity and specificity problems. There is increasing confidence in assigning uncomplicated cystic echinococcosis cysts to the four treatment modalities [drug treatment (benzimidazoles), percutaneous methods, surgery, watch and wait] on the basis of cyst stage (WHO cyst classification), size and location. However, current best practice is still not widely implemented outside cystic echinococcosis treatment centres, and further consolidation is needed by well-designed clinical trials. Recently published long-term follow-up studies have shown that patients with inactive cyst stages CE4 and CE5 benefit, especially since they do not need any treatment at all if they have not received prior benzimidazole or percutaneous therapy. Instead, cysts that have reached cyst stages CE4 and CE5 through drug treatment do need careful follow-up as they often relapse. Surgical procedures in which the cysts are opened and percutaneous approaches require very careful control of cyst content spillage to the peritoneum, pleura and intravascularly to prevent dissemination – a still too often neglected issue with severe consequences for patients.

Summary
Though a neglected disease with predominantly expert-opinion-based treatment strategies, cystic echinococcosis patients can greatly benefit from interdisciplinary management in cystic echinococcosis treatment centres and cyst-stage-based assignment of treatment modalities. Increased suspicion for cystic echinococcosis in migrants from endemic to non-endemic countries is urgently needed at the current level of global mobility.
Gadoxetic Acid–Enhanced Hepatobiliary-Phase Magnetic Resonance Imaging for Delineation of Focal Nodular Hyperplasia: Superiority of High-Flip-Angle Imaging
Authors: Sheng Ruofan , Palm Viktoria , Mayer Philipp , Mokry Theresa , Berger Anne Katrin , Weiss Karl Heinz , Longerich Thomas , Kauczor Hans Ulrich , Weber Tim Frederik 
Published: August 2018

Objective
The aim of this study was to investigate whether hepatobiliary-phase (HBP) flip-angle (FA) increase to 25° improves conspicuity of focal nodular hyperplasia (FNH) and enables HBP delay reduction.

Methods
This was a retrospective study of 23 patients with 46 FNHs. In each patient, HBP was performed with reduced-delay high FA (early/high), standard-delay high FA (late/high), and standard-delay standard FA (standard). Relative enhancement of liver and FNH periphery, FNH periphery–to–liver contrast ratio, and FNH periphery–to–central scar contrast ratio were compared between each HBP.

Results
Early/high, late/high, and standard HBPs were performed after 13.00 ± 2.12, 19.12 ± 3.10, and 19.68 ± 3.22 minutes, respectively. Liver and FNH periphery relative enhancement, FNH periphery–to–liver contrast ratio, and FNH periphery–to–central scar contrast ratio were higher for early/high and late/high than for standard HBP (P < 0.001 to P = 0.0048).

Conclusions
Increasing FA to 25° improves delineation of FNHs in HBP. Combining FA increase with delay reduction is superior to standard HBP and is sufficient for FNH characterization.
Accuracy of Digital Tomosynthesis of the Chest in Detection of Interstitial Lung Disease Comparison With Digital Chest Radiography
Authors: Kruamak Temphon , Edwards Rachael , Cheng Stephanie , Hippe Daniel S. , Raghu Ganesh , Pipavath Sudhakar N. J. 
Published: August 2018

Purpose
The aim of the study was to assess the ability of chest digital tomosynthesis (DTS) for detection of interstitial lung disease (ILD) compared with conventional chest radiography.

Materials and Methods
We retrospectively reviewed 78 patients (60 males, 18 females, mean age = 53.05 years, range, 19–83 years) who underwent chest DTS for a 5-year interval (January 1, 2009–December 31, 2014). Of the 78 patients, 33 (42.3%) carried a diagnosis of ILD and 45 (57.7%) were not ILD. All computed tomography reports and medical records were reviewed. The conventional chest radiography and DTS were separately reviewed by 2 radiologists for the presence of ILD and the confidence in diagnosis.

Results
The diagnostic accuracy of DTS for the detection of ILD was better than conventional chest radiography (P < 0.05). Digital tomosynthesis had a sensitivity of 83.3% and negative predictive value of 89.0% that were statistically significantly better than conventional chest radiography (43.9% and 70.9%, respectively). Confidence in diagnosing ILD at DTS was higher than conventional chest radiography (P < 0.001) and had higher interobserver agreement than conventional chest radiography (P < 0.01).

Conclusions
Digital tomosynthesis improves diagnostic performance and confidence in diagnosing ILD compared with conventional chest radiography. Digital tomosynthesis can be suggested as the initial diagnostic technique for patients with suspected ILD.