bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy and safety of irinotecan ± bevacizumab compared with oxaliplatin ± bevacizumab for metastatic colorectal cancer
Authors: Dai Jiali , Chen Yuetong , Gong Yang , Wei Jingsun , Cui Xiaowen , Yu Hualin , Zhao Wenjing , Gu Dongying , Chen Jinfei 
Published: September 2019

Abstract

Background:
Irinotecan (IRI)-based and oxaliplatin (OXA)-based regimens are available for the treatment of metastatic colorectal cancer (mCRC). Several studies have published inconsistent results in their comparisons of the efficacy and toxicity of IRI ± bevacizumab and OXA ± bevacizumab. This meta-analysis was performed to evaluate the efficacy and safety of these 2 regimens in patients with mCRC.

Methods:
We searched several databases to identify relevant studies, including PubMed, EMBASE, and the Cochrane Controlled Trials Register. The primary endpoints were overall survival (OS) and time to progression (TTP). The secondary comparisons were overall response rate (ORR) and toxicity. In addition, the hazard ratio (HR) or risk ratio (RR) values with their corresponding 95% confidence intervals (CIs) were extracted from these studies.

Results:
Pooled data of 13 studies demonstrated no significant differences in OS (HR = 0.96, 95% CI: 0.86–1.08, P = .53) and TTP (HR = 0.88, 95% CI: 0.72–1.08, P = .24) between the 2 groups. However, the ORR (RR = 0.87, 95% CI: 0.78–0.97, P = .02) was clearly improved in the OXA ± bevacizumab arm. Higher incidences of grade 3/4 nausea (RR = 1.63, 95% CI: 1.28–2.07, P < .001), vomiting (RR = 1.40, 95% CI: 1.09–1.81, P = .01), diarrhea (RR = 1.44, 95% CI: 1.23–1.70, P < .001), and anemia (RR = 4.13, 95% CI: 2.75–6.22, P < .001) were observed in the IRI group. However, the incidences of grade 3/4 neutropenia (RR = 0.75, 95% CI: 0.68–0.83, P < .001), thrombocytopenia (RR = 0.43, 95% CI: 0.26–0.73, P = .002), and paresthesia/neurological disturbances (RR = 0.04, 95% CI: 0.02–0.07, P < .001) were higher in the OXA group.

Conclusion:
This meta-analysis confirmed that the OXA ± bevacizumab regimen as a maintenance therapy significantly improved the ORR in patients with mCRC. Exhibiting strong efficacy and safety, the OXA and OXA plus bevacizumab regimens are preferred as first-line treatments for mCRC.
Delirium in a Tertiary PICU: Risk Factors and Outcomes*
Authors: Dervan Leslie A. , Di Gennaro Jane L. , Farris Reid W. D. , Watson R. Scott 
Published: September 2019

Objectives:
To determine risk factors and outcomes associated with delirium in PICU patients.

Design:
Retrospective cohort study.

Setting:
Thirty-two–bed PICU within a tertiary care academic children’s hospital.

Patients:
All children admitted to the PICU March 1, 2014, to October 1, 2016, with at least one Cornell Assessment of Pediatric Delirium score (n = 2,446).

Interventions:
None.

Measurements and Main Results:
Cornell Assessment of Pediatric Delirium score was performed twice daily as standard of care. We characterized delirium as: 1) presence of greater than or equal to 1 positive score (Cornell Assessment of Pediatric Delirium ≥ 9) and 2) number of days with a positive score. We built multivariable logistic and linear regression models using electronic medical records data. Many patients (n = 1,538; 63%) had a short length of stay (< 48 hr). Compared with patients with length of stay greater than or equal to 48 hours, fewer experienced delirium (30% vs 69%; p < 0.0001). Among 908 patients with length of stay greater than or equal to 48 hours, presence of delirium was independently associated with age less than 2 years old, baseline cognitive dysfunction, primary diagnosis, and duration of mechanical ventilation. Benzodiazepines demonstrated a dose-response effect (odds ratio for presence of delirium, 1.8 [p = 0.03], 3.4 [p < 0.001], and 9.7 [p = 0.005] for < 25th percentile, 25–75th percentile, and > 75th percentile of total dose, vs no exposure). In terms of outcomes, presence of delirium was independently associated with increased ICU length of stay (p < 0.001), whereas days of delirium were independently associated with decline in cognitive function from ICU admission to discharge (odds ratio, 1.06; p < 0.001), increased ICU (p < 0.001), and hospital length of stay (p < 0.001). Neither delirium presence nor total days were independently associated with mortality.

Conclusions:
Delirium is common in the PICU, particularly among patients with length of stay greater than or equal to 48 hours. It is independently associated with patient characteristics and PICU exposures, including benzodiazepines. The role of delirium as an independent causal factor in patient outcome requires further investigation.
Quality Improvement Interventions to Improve Critical Congenital Heart Disease Screening
Authors: Hom Lisa A. , Chan Salcedo Clarissa , Revenis Mary , Martin Gerard R. 
Published: September 2019

Introduction:
Newborn screening for critical congenital heart disease (CCHD) using pulse oximetry improves detection and is associated with decreased related infant mortality. In 2015, the Healthy Hearts of Babies Act required hospitals to screen all newborns in the District of Columbia for CCHD using pulse oximetry and to provide documentation of individual screening results to the Department of Health. A regulatory report from the electronic health record revealed an opportunity to improve both documentation and protocol adherence within our hospital. We aimed to reduce documentation errors and protocol violations by 75% and sustain this improvement for 6 months.

Methods:
In February of 2014, our center, a large free-standing children’s hospital, implemented CCHD screening in the neonatal intensive care unit on all infants without known congenital heart disease or receiving supplemental oxygen. During the intervention period (January 2016 to December 2018), an interdisciplinary team engaged in regular review and analysis of reports, monthly closed-loop feedback, and iterative refinements to the electronic health record. Statistical process control charts were used to compare a baseline period to the intervention period and track monthly progress.

Results:
Between February 2014 and December 2018, we screened 2,214 infants for CCHD. The average percentage of documentation errors decreased from 23.5% during the baseline period to 1.2% during the intervention period, a sustained reduction for over 2 years. Protocol violations occurred at an average of 2.1% in the baseline period, with a sustained decrease to 0.6% during the intervention period.

Conclusions:
This multimodal quality improvement project demonstrated a sustained reduction of CCHD screening documentation errors and protocol violations.
Postoperative Management of Zygomatic Arch Fractures: In-House Rapid Prototyping System for the Manufacture of Protective Facial Shields
Authors: Orabona Giovanni Dell’Aversana , Abbate Vincenzo , Maglitto Fabio , Committeri Umberto , Improta Giovanni , Bonavolontà Paola , Reccia Alfonso , Somma Teresa , Iaconetta Giorgio , Califano Luigi 
Published: September 2019

Abstract
Zygomatic fractures account for 10% to 15% of all facial fractures. The surgical management of isolated zygomatic arch fractures usually requires open reduction treatment without fixation through an intraoral access. Therefore, the main problem in the non-fixed treatment of zygomatic arch fractures is related to the difficulty in obtaining a stable reduction for a period long enough to guarantee the physiological bone healing process. We propose an innovative “in-house” rapid prototyping (RP) protocol for the 3D-zygoma mask manufacture of a patient-specific protective device to apply after zygomatic arch fracture reduction. Our study includes 16 consecutive patients who underwent surgical open reduction for an isolated zygoma fracture without fixation between January 2017 and February 2018. The patients received regular postoperative checks at weeks 1 and 2. Before the device was removed, a multiple choice questionnaire was administered to measure the degree of wearability of the mask. The estimated cost of the production is around €5 per case and the construction time is around 90 minutes. Based on the encouraging results, obtained in our experience, we hope that other studies can be conducted to confirm our procedure and improve its functionality in the field of facial trauma.
Histologic Evaluation of Healing Lip Defects Treated With Injected Onabotulinum Toxin A and Topical Mitomycin C
Authors: Jahanbin Arezoo , Namdar Parastoo , Ghazi Narges , Kazemian Mozhgan 
Published: September 2019

Objective:
Using an experimental rat model, the efficacy of injected Onabotulinum Toxin A (BoNT-A) versus topical Mitomycin C in surgical wound healing of rat lip defects was evaluated.

Methods and Materials:
Sixty-seven male Wister rats received a triangular cut (7 × 7 × 4 mm) on their upper lip. Then they were divided randomly into 4 equal groups: group A (topical Mitomycin C plus injected BoNT-A); group B (topical Mitomycin C); group C or control group (saline solution) and group D (injected (BoNT-A). After 3 months, the animals were euthanized and scars were evaluated using hematoxylin and eosin and Masson's trichrome.
For qualitative analysis, inflammatory cell density, new capillary formation, fibroblast proliferation, and collagen deposition were reported using relative ranks from 0 to 3 (absence, mild, moderate, marked). Data were analyzed by post hoc and Kruskal–Wallis tests. The significance level was P < 0.05.

Result:
Mean collagen deposition values and fibroblast proliferation in the 4 groups showed statistically significant differences with each other (P value < 0.001). A significant difference between group A and controls existed for fibroblast proliferation (median 1 versus 2, P value < 0.001); also, collagen deposition (median 1 versus 2, P value < 0.001). A significant difference existed between the control and group D (median 2 versus 1, P value = 0.004); also, group A and B (median 1 versus 2, P value = 0.002) for collagen deposition. However, no significant differences existed between the 4 groups regarding inflammatory cells and angiogenesis (P value > 0.05).

Conclusion:
Local injection of BoNT-A plus Mitomycin C followed by BoNT-A alone provided less collagen formation and fibroblastic proliferation in the healing lip defect in a rat model.
A Small Dose of Butorphanol Prevents Sufentanil-induced Cough During General Anesthesia Induction
Authors: Yin Fang , Zhang Tiejun 
Published: September 2019

Purpose:
This study aimed to evaluate the suppressive effects of a small dose of butorphanol on sufentanil-induced cough during general anesthesia induction.

Methods:
120 patients who were scheduled for elective maxillofacial surgery of American Society of Anesthesiologists I∼II, aged 18∼65 years were randomly divided into 3 groups (n = 40). Patients received butorphanol 0.1 mg (group I), 1 mg (group II) or an equal volume of 0.9% normal saline (group III) 5 seconds right before sufentanil bolus (0.5ug/kg). Sufentanil was diluted into 5ug/mL and administrated within 5 seconds. The incidence and reflex degree of cough in all groups were evaluated within 2 minutes after the injection of sufentanil during anesthesia induction. Mean arterial pressure (MAP) and heart rate (HR) were recorded at T0 (before the injection of butorphanol or normal saline), T1 (before the injection of sufentanil) and T2 (2 minutes after sufentanil injection).

Results:
The HR and MAP values were no significant difference among the 3 groups at the same observation point. In group II, the HR decreased significantly at T2 compared with T0 and T1 (P <0.05, T2 VS T0, T1). None of the patients in group I and group II had cough, and 33 patients in group III developed cough, of which 12.5% were mild, 40% were moderate, and 30% were severe.

Conclusions:
The results of present study suggest that a small dose of butorphanol 0.1 mg can prevent sufentanil-induced cough and ensure a relatively stable hemodynamic state during general anesthesia induction.
Identification and Recent Approaches for Evaluation, Operative Counseling, and Management in Patients With Freeman-Burian Syndrome: Principles for Global Treatment
Authors: Poling Mikaela I. , Dufresne Craig R. , Portillo Augusto L. 
Published: September 2019

Abstract
For many, the experience of a complex craniofacial malformation condition, such as Freeman-Burian syndrome (FBS), formerly Freeman-Sheldon syndrome, is deeply distressing. There are few references in the literature addressing initial evaluation and operative counseling for FBS, and guidance is absent. Two major outcomes of FBS are explored, namely diagnostic accuracy and therapeutic result, to identify factors influencing optimal clinical care in (1) diagnosis, (2) evaluation, (3) general and craniofacial operative counseling, and (4) craniofacial management.
PubMed searches have yielded 15 results describing craniofacial surgery in FBS and 29 manuscripts describing psychosocial aspects of surgery and patient and family counseling and education in other non-intellectually impairing craniofacial malformation conditions. Research in this area of scholarship is plagued by problems, especially considerable knowledge gaps and an absence of study data for operative outcomes. As a result, the literature remains unsettled, though our experience presents a much more clear picture of the clinical reality for this challenging patient population. While many challenges and limitations to treatment are present, much can be done to afford these patients a good and productive quality of life through operative intervention and longitudinal psychosocial support.
Ancient genomic regulatory blocks are a major source for gene deserts in vertebrates after whole genome duplications
Authors: Touceda-Suárez María , Kita Elizabeth M. , Acemel Rafael D. , Firbas Panos N. , Magri Marta S. , Naranjo Silvia , Tena Juan J. , Gómez-Skarmeta Jose Luis , Maeso Ignacio , Irimia Manuel 
Published: September 2019

AbstractWe investigated how the two rounds of whole genome duplication that occurred at the base of the vertebrate lineage have impacted ancient microsyntenic associations involving developmental regulators (known as genomic regulatory blocks, GRBs). We showed that the majority of GRBs present in the last common ancestor of chordates have been maintained as a single copy in humans. We found evidence that dismantling of the additional GRB copies occurred early in vertebrate evolution often through the differential retention of the regulatory gene but loss of the bystander gene’s exonic sequences. Despite the large evolutionary scale, the presence of duplicated highly conserved non-coding regions provided unambiguous proof for this scenario for dozens of ancient GRBs. Remarkably, the dismantling of ancient GRB duplicates has contributed to the creation of large gene deserts associated with regulatory genes in vertebrates, providing a widespread mechanism for the origin of these enigmatic genomic traits.
Understanding artificial mouse-microbiome heterogeneity and six actionable themes to increase study power
Authors: Basson Abigail R , LaSalla Alexandria , Lam Gretchen , Kulpins Danielle , Moen Erika L , Sundrud Mark , Miyoshi Jun , Ilic Sanja , Theriault Betty R , Cominelli Fabio , Rodriguez-Palacios Alexander 
Published: September 2019

ABSTRACTThe negative effects of data clustering due to (intra-class/spatial) correlations are well-known in statistics to interfere with interpretation and study power. Therefore, it is unclear why housing many laboratory mice (≥4), instead of one-or-two per cage, with the improper use/reporting of clustered-data statistics, abound in the literature. Among other sources of ‘artificial’ confounding, including cyclical oscillations of the ‘cage microbiome’, we quantified the heterogeneity of modern husbandry practices/perceptions. The objective was to identify actionable themes to re-launch emerging protocols and intuitive statistical strategies to increase study power. Amenable for interventions, ‘cost-vs-science’ discordance was a major aspect explaining heterogeneity and the reluctance to change. Combined, four sources of information (scoping-reviews, professional-surveys, expert-opinion, and ‘implementability-score-statistics’) indicate that a six-actionable-theme framework could minimize ‘artificial’ heterogeneity. With a ‘Housing Density Cost Simulator’ in Excel and fully annotated statistical examples, this framework could reignite the use of ‘study power’ to monitor the success/reproducibility of mouse-microbiome studies.
Shadow enhancers suppress input transcription factor noise through distinct regulatory logic
Authors: Waymack Rachel , Fletcher Alvaro , Enciso German , Wunderlich Zeba 
Published: September 2019

AbstractShadow enhancers, groups of seemingly redundant enhancers, are found in a wide range of organisms and are critical for robust developmental patterning. However, their mechanism of action is unknown. We hypothesized that shadow enhancers drive consistent expression levels by buffering upstream noise through a separation of transcription factor (TF) inputs at the individual enhancers. By measuring transcriptional dynamics of several Kruppel shadow enhancer configurations in live Drosophila embryos, we showed individual member enhancers act largely independently. We found that TF fluctuations are an appreciable source of noise that the shadow enhancer pair can better buffer than duplicated enhancers. The shadow enhancer pair is uniquely able to maintain low levels of expression noise across a wide range of temperatures. A stochastic model demonstrated the separation of TF inputs is sufficient to explain these findings. Our results suggest the widespread use of shadow enhancers is partially due to their noise suppressing ability.
The HLA Ligand Atlas - A resource of natural HLA ligands presented on benign tissues
Authors: Marcu Ana , Bichmann Leon , Kuchenbecker Leon , Kowalewski Daniel Johannes , Freudenmann Lena Katharina , Backert Linus , Mühlenbruch Lena , Szolek András , Lübke Maren , Wagner Philipp , Engler Tobias , Matovina Sabine , Wang Jian , Hauri-Hohl Mathias , Martin Roland , Kapolou Konstantina , Walz Juliane Sarah , Velz Julia , Moch Holger , Regli Luca , Silginer Manuela , Weller Michael , Löffler Markus W. , Erhard Florian , Schlosser Andreas , Kohlbacher Oliver , Stevanović Stefan , Rammensee Hans-Georg , Neidert Marian Christoph 
Published: September 2019

ABSTRACTThe human leukocyte antigen (HLA) complex controls adaptive immunity by presenting defined fractions of the intracellular and extracellular protein content to immune cells. Here, we describe the HLA Ligand Atlas, an extensive collection of mostly matched HLA-I and -II ligandomes from 225 benign samples (29 tissues, 21 subjects). The initial release covers 51 HLA-I and 86 HLA-II allotypes presenting 89,853 HLA-I- and 140,861 HLA-II ligands. We observe that the immunopeptidomes differ considerably between tissues and individuals on both source protein and HLA-ligand level. 1,407 HLA-I ligands stem from non-canonical genomic regions. We highlight the importance of comparatively analyzing both benign and malignant tissues to inform tumor association, based on a case study in three glioblastoma patients. The resource provides insights into applied and basic immune-associated questions in the context of cancer immunotherapy, infection, transplantation, allergy, and autoimmunity. It is publicly available atwww.hla-ligand-atlas.org.
The mood stabilizer lithium slows down synaptic vesicle cycling at glutamatergic synapses
Authors: Tang Willcyn , Cory Bradley , Lim Kah Leong , Fivaz Marc 
Published: September 2019

AbstractLithium is a mood stabilizer broadly used to prevent and treat symptoms of mania and depression in people with bipolar disorder (BD). Little is known, however, about its mode of action. Here, we analyzed the impact of lithium on synaptic vesicle (SV) cycling at presynaptic terminals releasing glutamate, a neurotransmitter previously implicated in BD and other neuropsychiatric conditions. We used the pHluorin-based synaptic tracer vGpH and a fully automated image processing pipeline to quantify the effect of lithium on both SV exocytosis and endocytosis in hippocampal neurons. We found that lithium selectively reduces SV exocytic rates during electrical stimulation, and markedly slows down SV recycling post-stimulation. Analysis of single bouton responses revealed the existence of functionally distinct excitatory synapses with varying sensitivity to lithium ― some terminals show responses similar to untreated cells, while others are markedly impaired in their ability to recycle SVs. While the cause of this heterogeneity is unclear, these data indicate that lithium interacts with the SV machinery and influences glutamate release in a large fraction of excitatory synapses. Together, our findings show that lithium down modulates SV cycling, an effect consistent with clinical reports indicating hyperactivation of glutamate neurotransmission in BD.
dotdotdot: an automated approach to quantify multiplex single molecule fluorescent in situ hybridization (smFISH) images in complex tissues
Authors: Maynard Kristen R. , Tippani Madhavi , Takahashi Yoichiro , Phan BaDoi N. , Hyde Thomas M. , Jaffe Andrew E. , Martinowich Keri 
Published: September 2019

ABSTRACTMultiplex single-molecule fluorescent in situ hybridization (smFISH) is a powerful method for validating RNA sequencing and emerging spatial transcriptomic data, but quantification remains a computational challenge. We present a framework for generating and analyzing smFISH data in complex tissues while overcoming autofluorescence and increasing multiplexing capacity. We developed dotdotdot (https://github.com/LieberInstitute/dotdotdot) as a corresponding software package to quantify RNA transcripts in single nuclei and perform differential expression analysis. We first demonstrate robustness of our platform in single mouse neurons by quantifying differential expression of activity-regulated genes. We then quantify spatial gene expression in human dorsolateral prefrontal cortex (DLPFC) using spectral imaging and dotdotdot to mask lipofuscin autofluorescence. We lastly apply machine learning to predict cell types and perform downstream cell type-specific expression analysis. In summary, we provide experimental workflows, imaging acquisition and analytic strategies for quantification and biological interpretation of smFISH data in complex tissues.
Improved genome assembly and annotation of the soybean aphid (Aphis glycinesMatsumura)
Authors: Mathers Thomas C. 
Published: September 2019

AbstractAphids are an economically important insect group due to their role as plant disease vectors. Despite this economic impact, genomic resources have only been generated for a small number of aphid species. The soybean aphid (Aphis glycinesMatsumura) was the third aphid species to have its genome sequenced and the first to use long-read sequence data. However, version 1 of the soybean aphid genome assembly has low contiguity (contig N50 = 57 KB, scaffold N50 = 174 KB), poor representation of conserved genes and the presence of genomic scaffolds likely derived from parasitoid wasp contamination. Here, I use recently developed methods to reassemble the soybean aphid genome. The version 2 genome assembly is highly contiguous, containing half of the genome in only 40 scaffolds (contig N50 = 2.00 Mb, scaffold N50 = 2.51 Mb) and contains 11% more conserved single copy arthropod genes than version 1. To demonstrate the utility this improved assembly, I identify a region of conserved synteny between aphids andDrosophilacontaining members of theOsirisgene family that was split over multiple scaffolds in the original assembly. The improved genome assembly and annotation ofA. glycinesdemonstrates the benefit of applying new methods to old data sets and will provide a useful resource for future comparative genome analysis of aphids.