bluuebunny/crossref_metadata_2025 huggingface dataset:
Decoding the epitranscriptional landscape from native RNA sequences
Authors: Jenjaroenpun Piroon , Wongsurawat Thidathip , Wadley Taylor D , Wassenaar Trudy M , Liu Jun , Dai Qing , Wanchai Visanu , Akel Nisreen S , Jamshidi-Parsian Azemat , Franco Aime T , Boysen Gunnar , Jennings Michael L , Ussery David W , He Chuan , Nookaew Intawat
Published: July 2020

Traditional epitranscriptomics relies on capturing a single RNA modification by antibody or chemical treatment, combined with short-read sequencing to identify its transcriptomic location. This approach is labor-intensive and may introduce experimental artifacts. Direct sequencing of native RNA using Oxford Nanopore Technologies (ONT) can allow for directly detecting the RNA base modifications, although these modifications might appear as sequencing errors. The percent Error of Specific Bases (%ESB) was higher for native RNA than unmodified RNA, which enabled the detection of ribonucleotide modification sites. Based on the %ESB differences, we developed a bioinformatic tool, epitranscriptional landscape inferring from glitches of ONT signals (ELIGOS), that is based on various types of synthetic modified RNA and applied to rRNA and mRNA. ELIGOS is able to accurately predict known classes of RNA methylation sites (AUC > 0.93) in rRNAs from Escherichiacoli, yeast, and human cells, using either unmodified in vitro transcription RNA or a background error model, which mimics the systematic error of direct RNA sequencing as the reference. The well-known DRACH/RRACH motif was localized and identified, consistent with previous studies, using differential analysis of ELIGOS to study the impact of RNA m6A methyltransferase by comparing wild type and knockouts in yeast and mouse cells. Lastly, the DRACH motif could also be identified in the mRNA of three human cell lines. The mRNA modification identified by ELIGOS is at the level of individual base resolution. In summary, we have developed a bioinformatic software package to uncover native RNA modifications.
Giant Fusiform and Dolichoectatic Aneurysms of the Basilar Trunk and Vertebrobasilar Junction—Clinicopathological and Surgical Outcome
Authors: Nakatomi Hirofumi , Kiyofuji Satoshi , Ono Hideaki , Tanaka Minoru , Kamiyama Hiroyasu , Takizawa Katsumi , Imai Hideaki , Saito Nobuhito , Shiokawa Yoshiaki , Morita Akio , Flemming Kelly D , Link Michael J
Published: July 2020

BACKGROUND

Giant fusiform and dolichoectatic aneurysms of the basilar trunk and vertebrobasilar junction (BTVBJ-GFDA) are extremely difficult to treat.

OBJECTIVE

To evaluate factors influencing survival and outcome of BTVBJ-GFDA by performing a retrospective multicenter cohort study.

METHODS

A total of 32 patients with BTVBJ-GFDA were included in this study. Clinicopathological characteristics, treatment measures, and outcomes were collected from medical records and imaging studies. Autopsy and histological findings of the aneurysm and adjacent brain tissue were also obtained in 9 cases.

RESULTS

A total of 11 patients did not undergo surgery, of whom 10 died; 3 from progressive brainstem compression, 4 from subarachnoid hemorrhage, 2 from brainstem infarction, and 1 from associated atherosclerotic disease. The remaining 21 patients underwent a surgical treatment, consisting of immediately proximal parent artery occlusion, remotely proximal parent artery occlusion, clip reconstruction, and distal bypass and achieved significantly longer overall survival compared with those who received conservative therapy (adjusted hazard ratio 1.508, 95% CI 1.058-2.148, P = .02). Histological examination of the aneurysms demonstrated staged clots, open lumen, and intrathrombotic channels with endothelial lining. The patients younger than 45 yr of age showed statistically longer survival than those equal and older than 45 yr (P = .03).

CONCLUSION

Surgical intervention achieved greater survival than conservative management in BTVBJ-GFDA. Narrow ideal treatment window of the blood flow within the aneurysm to maintain sufficient but not excess supply should be targeted based on the hemodynamics of both the posterior communicating arteries and perforating vessel collaterals.
Out of the West: Formation of a Permanent Plague Reservoir in South-Central Germany (1349–1356) and its Implications
Authors: Slavin Philip
Published: July 2020

This article deals with the origins and spread of the second outbreak of fourteenth-century plague pandemic, the pestis secunda, which swept over West Eurasia and North Africa between 1356 and 1366. Unlike the Black Death, its immediate predecessor, which seems to have originated in Central Asia, the pestis secunda emerged in Central Germany, most likely in the Frankfurt region, in summer 1356. Having seeded its new reservoir, the plague radiated from Central Germany, a landlocked region, into other parts of West Eurasia and North Africa, via inland routes. The inland mode of transmission is at odds with the geographic spread of the Black Death, whereby the plague arrived in West Eurasian and North African ports via maritime trade routes. To appreciate the appearance of the Central Germany plague reservoir in the early 1350s, the wider ecological, climatic and socio-economic context of the Frankfurt region is scrutinized, on the basis of textual, palaeoclimatic and palaeogenetic evidence. Although beyond the remit of this article, it argues that the Central German reservoir may have become the origin of recurrent late-medieval and early-modern plague outbreaks.
Social optimism biases are associated with cortical thickness
Authors: Moser Dominik Andreas , Dricu Mihai , Wiest Roland , Schüpbach Laurent , Aue Tatjana
Published: July 2020

Optimism biases denote the tendency to see future desirable events as being more likely to happen to oneself than undesirable events. Such biases are important for mental health and may extend to other individuals or social groups (social optimism biases). However, little is known about whether social optimism biases relate to brain structure. Using sparse canonical correlation analysis, we associated cortical thickness (assessed by magnetic resonance imaging) with measures of social and personal optimism bias, trait optimism and related concepts. We identified a defensive self-enhancement dimension that associated significantly and reliably with the cortical thickness of the insula and inferior frontal cortex. This self-enhancement dimension included unfavorable biases toward unpopular out-groups and indicators of personal optimism and pessimism. A shared biological substrate underlying future expectancies that subserves the promotion of the self and the denigration of unpopular out-groups may render society-wide efforts to counteract stereotyping particularly difficult: such efforts may hinder the establishment of adaptive personal optimism biases.
Attentional conditions differentially affect early, intermediate and late neural responses to fearful and neutral faces
Authors: Schindler Sebastian , Bruchmann Maximilian , Steinweg Anna-Lena , Moeck Robert , Straube Thomas
Published: July 2020

The processing of fearful facial expressions is prioritized by the human brain. This priority is maintained across various information processing stages as evident in early, intermediate and late components of event-related potentials (ERPs). However, emotional modulations are inconsistently reported for these different processing stages. In this pre-registered study, we investigated how feature-based attention differentially affects ERPs to fearful and neutral faces in 40 participants. The tasks required the participants to discriminate either the orientation of lines overlaid onto the face, the sex of the face or the face’s emotional expression, increasing attention to emotion-related features. We found main effects of emotion for the N170, early posterior negativity (EPN) and late positive potential (LPP). While N170 emotional modulations were task-independent, interactions of emotion and task were observed for the EPN and LPP. While EPN emotion effects were found in the sex and emotion tasks, the LPP emotion effect was mainly driven by the emotion task. This study shows that early responses to fearful faces are task-independent (N170) and likely based on low-level and configural information while during later processing stages, attention to the face (EPN) or—more specifically—to the face’s emotional expression (LPP) is crucial for reliable amplified processing of emotional faces.
Local trusts and forced heirship (Commentary to the “CRO” case)  C. R. O. c/C. O. N. y otros s/nulidad de acto jurídico (22 October 2019) Court: Civil and Commercial Law, Chamber of Appeals of Necochea (Buenos Aires Province—Argentina)
Authors: Malumian Nicolas
Published: July 2020

This recent case is a leading case relating to local trusts and forced heirship. Forced heirship is a restriction to the liberty to write a will and determine the destiny of his/her future estate by the testator. It can be found in all South America (not in Latin America from Panama to México) and in most Civil Law countries in Europe, besides similar restrictions under sharia law. The way to avoid these restrictions has been the creation of a foreign trust over foreign assets. Although authors have long analyzed whether a local trust allows the avoidance of local forced heirship rules over local assets, there has been no case law in this respect (at least since the inclusion of the trust in Argentine law in 1995). In short, this is the first time a local trust over local assets has been under the scrutiny of the courts to determine if there is a violation of forced heirship.
Sham trust in Argentina (Commentary to the “Itik SRL” case) “Sindicatura in Itik SRL c/Romero, Carlos y Otros. Acción de inoponibilidad por fraude” (5 May 2020) Court: Civil and Commercial Chamber of Appeals 9th Circuit (Cordoba Province—Argentina)
Authors: Malumian Nicolas
Published: July 2020

In the Common Law world, there are many antecedents regarding sham trusts and a huge body of analysis. Therefore, it might be surprising to learn that the situation is completely different in the Civil Law world. The relevance of this case is that it is one of the very few in which a trust is subject to legal scrutiny and declared a sham.
Economic Impact of Fluopyram-Amended Seed Treatments to Reduce Soybean Yield Loss Associated with Sudden Death Syndrome
Authors: Baetsen-Young Amy M. , Swinton Scott M. , Chilvers Martin I.
Published: July 2020

Soybean (Glycine max) sudden death syndrome (SDS), caused by Fusarium virguliforme, is a key limitation in reaching soybean yield potential, stemming from incomplete disease management through cultural practices and partial host resistance. A fungicidal seed treatment was released in 2014 with the active ingredient fluopyram and was the first chemical management strategy to reduce soybean yield loss stemming from SDS. Although farm level studies have found fluopyram profitable, we were curious to discover whether fluopyram would be beneficial nationally if targeted to soybean fields at risk for SDS yield loss. To estimate economic benefits of fluopyram adoption in SDS at-risk acres, in the light of U.S. public research and outreach from a privately developed product, we applied an economic surplus approach, calculating ex ante net benefits from 2018 to 2032. Through this framework of logistic adoption of fluopyram for alleviation of SDS-associated yield losses, we projected a net benefit of $5.8 billion over 15 years, considering the costs of public seed treatment research and future extension communication. Although the sensitivity analysis indicates that overall net benefits from fluopyram adoption on SDS at-risk acres are highly dependent upon the market price of soybean, the incidence of SDS, the adoption path, and ceiling of this seed treatment, the net benefits still exceeded $407 million in the worst-case scenario.
Natural Occurrence of Maize Gibberella Ear Rot and Contamination of Grain with Mycotoxins in Association with Weather Variables
Authors: Dalla Lana F. , Madden L. V. , Paul P. A.
Published: July 2020

Gibberella ear rot (GER) severity (percent area of the ear diseased) and associated grain contamination with mycotoxins were quantified in plots of 15 to 16 maize hybrids planted at 10 Ohio locations from 2015 to 2018. Deoxynivalenol (DON) was quantified in grain samples in all 4 years, whereas nivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol (15ADON) were quantified only in the last 2 years. Only DON and 15ADON were detected. The highest levels of GER and DON contamination were observed for 2018, followed by 2016 and 2017. No GER symptoms or DON were detected in 2015. Approximately 41% of the samples from asymptomatic ears had detectable levels of DON, and 7% of these samples from 2016 had DON > 5 ppm. Associations between DON contamination and 43 variables representing summaries of temperature (T), relative humidity (RH), rainfall (R), surface wetness, and T-RH combinations for different window lengths and positions relative to R1 growth stage were quantified with Spearman correlation coefficients (r). Fifteen-day window lengths tended to show the highest correlations. Most of the variables based on T, R, RH, and T-RH were significantly correlated with DON for the 15-day window, as well as other windows. For moisture-related variables, there generally was a negative correlation before R1, changing to a positive correlation after R1. Results showed that GER and DON can be frequently found in Ohio maize fields, with the risk of DON being associated with multiple weather variables, particularly those representing combinations of T between 15 and 30°C and RH > 80 summarized during the 3 weeks after R1.
An Examination of Simulation Prebriefing in Nursing Education: An Integrative Review
Authors: Dileone Christine , Chyun Deborah , Diaz Desiree A. , Maruca Annette T.
Published: July 2020

AIM

The aim of the integrative review was to examine the prebriefing phase of simulation as the foundation for the learning experience of nursing students and to determine effective prebriefing activities to enhance learning.

BACKGROUND

There are currently no frameworks or specific time allotments for prebriefing comparable to those implemented for debriefing.

METHOD

Eight electronic databases were searched for the period 2012 to 2019. Six studies were selected based on relevance and inclusion. Whittemore and Knafl’s integrative review framework was used for data analysis.

RESULTS

The studies reviewed answer how to effectively prepare students for simulation to enhance their learning and have a positive effect on clinical judgment and self-confidence; yet, prebriefing is not considered the foundation of the simulation experience.

CONCLUSION

A well-designed prebriefing process is essential to high-quality simulation experiences. Standardization of this process has yet to be established.
Shoulder Dysfunction in Breast Cancer Survivors: Can Treatment Type or Musculoskeletal Factors Identify Those at Higher Risk?
Authors: Lang Angelica E. , Murphy Maybelle , Dickerson Clark R. , Stavness Ian , Kim Soo Y.
Published: July 2020

Background and Objective:

Breast cancer is the most commonly diagnosed cancer in Canadian women. Breast cancer survivors are known to experience shoulder dysfunction, but the influence of musculoskeletal and treatment factors has yet to be investigated in a Saskatchewan population, which was the purpose of this study.

Methods:

Two study designs were used to assess risk factors for dysfunction: (1) a cross-sectional Web-based questionnaire and (2) prospective cohort analysis of preoperative musculoskeletal assessment combined with postoperative Shoulder Pain and Disability Index (SPADI) score. Data from the survey were summarized and analyzed using χ2 tests (P < .05), while nonparametric measures were used to calculate temporal differences and associations between musculoskeletal risk factors and disability.

Results:

Commonly reported shoulder problems after treatment were stiffness (63.5%), restricted range of motion (61.9%), and changes in arm/hand sensation (61.9%). Axillary lymph node dissection and radiation therapy were associated with more shoulder problems than other treatment types. SPADI scores increased by an average of 8.1% from baseline to 3 months postsurgery. A clinically significant 18% increase between these time points was moderately associated with a history of shoulder problems and restricted humeral extension preoperatively (average = 37.7° vs 48.9°).

Conclusions:

Breast cancer survivors from Saskatchewan have a high prevalence of shoulder problems following treatment. Clinically significant impairments in shoulder function are associated with select treatment types and preoperative impairments. These results can be used to identify high-risk patients before cancer treatment and direct their rehabilitation.
Exploring the Physical Therapy Experience Among People Living With Lymphedema: A Biopsychosocial Perspective
Authors: Donlan Pamela , Cohn Yael , Doukas Nicole
Published: July 2020

Background:

Lymphedema is a chronic condition that adversely affects quality of life and can negatively impact psychosocial well-being. The influence of physical therapy (PT) experience upon people living with lymphedema warrants exploration. Physical therapists play a significant role in the management of this disease, PT interventions have been shown to affect quality of life in this population, and the PT experience has had meaningful consequences across a spectrum of people living with chronic disease or disability.

Objectives:

The purpose of this study was to explore the psychosocial effect of the PT experience on people living with lymphedema.

Methods:

A qualitative approach, using conventional descriptive content analysis, was used. Purposeful sampling was used to recruit 8 participants from the Northeast United States. Data were collected through semistructured individualized interviews, and iterative analysis was used to create themes and subthemes that were inclusive of all data.

Results:

Through inductive category development, 3 major themes emerged. Major themes were as follows: (1) coping strengthened by understanding; (2) quality of life enhanced by education; and (3) lack of person-centered approach as a barrier to progress.

Limitations:

While trustworthiness measures were in place, it is difficult to completely eliminate bias when using qualitative methodology.

Conclusions:

Among people living with lymphedema, PT plays a significant role in addressing the psychosocial factors that impact participation in life events. Physical therapists should focus upon professional development that can enhance person-centered communication and interpersonal skills so that more successful outcomes can be achieved.
Perioperative Risk Factors Associated With Acute Kidney Injury in Patients After Brain Tumor Resection
Authors: Li Jiaxin , Zhao Yan , Yan Xiang , Li Ruowen , Zhang Xingyue , Zeng Min , Dong Jia , Li Shu , Peng Yuming , Han Ruquan
Published: July 2020

Background:

Acute kidney injury (AKI) is a serious complication after surgery. The aim of this study is to identify risk factors for postoperative AKI in patients undergoing brain tumor surgery.

Methods:

This single-center, retrospective, matched case-control study included patients undergoing elective brain tumor surgery between January 2016 and December 2018 at Beijing Tiantan Hospital, Capital Medical University, China. Patients developing postoperative AKI were compared with controls without AKI matched by age, sex, and date of surgery in a ratio of 1:3. AKI was defined using the Kidney Disease Improving Global Outcomes criteria.

Results:

A total of 9933 patients were identified for review, of which 115 (1.16%) developed AKI; 345 matched patients were included in the control group. AKI occurred most commonly within the first 24 hours (41/97, 42.3%) and 48 hours (33/94, 35.1%) after surgery. Preoperative administration of mannitol (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.04-2.60; P= 0.034), American Society of Anesthesiologists physical status III or higher (OR, 5.50; 95% CI, 2.23-13.59; P<0.001), preoperative blood glucose (OR, 2.53; 95% CI, 1.23-5.22; P=0.012), craniopharyngioma (OR, 8.96; 95% CI, 3.55-22.63; P<0.001), nonsteroidal anti-inflammatory drug administration (OR, 3.74; 95% CI, 1.66-8.42; P<0.001), and intraoperative hypotension (OR, 2.13; 95% CI, 1.21-3.75; P=0.009) were independent risk factors for postoperative AKI.

Conclusion:

Multiple factors, including preoperative administration of mannitol, are independently associated with the development of postoperative AKI in patients undergoing brain tumor surgery.
Update on the treatment of nonsystemic juvenile idiopathic arthritis including treatment-to-target: is (drug-free) inactive disease already possible?
Authors: Klein-Wieringa Inge R. , Brinkman Danielle M.C. , ten Cate Rebecca , Hissink Muller Petra C.E.
Published: July 2020

Purpose of review

This review concerns the outcome for nonsystemic juvenile idiopathic arthritis (JIA) with emphasis on treatment-to-target (T2T) and treatment strategies aiming at inactive disease by giving an overview of recent articles.

Recent findings

More efficacious therapies and treatment strategies/T2T with inactive disease as target, have improved the outcome for JIA significantly. Recent studies regarding treatment strategies have shown 47–68% inactive disease after 1 year. Moreover, probability of attaining inactive disease at least once in the first year seems even higher in recent cohort-studies, reaching 80%, although these studies included relatively high numbers of oligoarticular JIA patients. However, 26–76% of patients flare upon therapy withdrawal and prediction of flares is still difficult.

Remission can be achieved and sustained in (some) JIA patients, regardless of initial treatment. Cornerstone principles in the management of nonsystemic JIA treatment are early start of DMARD therapy, striving for inactive disease and T2T by close and repeated monitoring of disease activity. T2T and tight control appear to be more important than a specific drug in JIA. Next to inactive disease, it is important that patients/parents are involved in personal targets, like reduction of pain and fatigue. Future studies should focus on predictors (based on imaging-methods or biomarkers) for sustained drug-free remission and flare.
Association Between Femoral “Spike” Size After Intramedullary Nailing and Subsequent Knee Motion Surgery
Authors: Schloss Michael G. , O'Hara Nathan N. , Zaidi Syed M. R. , Hannan Zachary D. , Marinos Dimitrius , Atchison Jared , Mulliken Alexandra , Nascone Jason W. , O'Toole Robert V.
Published: July 2020

Objectives:

To determine the association between displaced femoral shaft bone fragments (“spikes”) seen on radiographs after intramedullary nail insertion and the need for future motion surgery.

Design:

Retrospective case–control study.

Setting:

Academic trauma center.

Patients:

We included patients with femoral shaft fractures treated with intramedullary nail insertion. Case patients (n = 22) had developed knee stiffness treated with motion surgery. The control group was a randomly selected sample (1:3 ratio).

Main Outcome Measures:

Motion surgery to address knee stiffness. We defined a “spike distance ratio” and “spike area ratio” from initial postoperative anteroposterior and lateral radiographs. Multivariable logistic regression determined the effect of spike distance and area ratios on the likelihood of need for motion surgery, controlling for polytraumatic injuries and bilateral fractures.

Results:

The case group had a median femoral spike distance ratio of 1.9 [interquartile range (IQR), 1.6–2.5] compared with 1.5 (IQR, 1.2–1.8) in the control group. An increased femoral spike distance ratio was associated with increased odds of motion surgery (P < 0.01). A femoral spike distance >2 times the femoral radius had 32 times the odds (95% confidence interval, 2–752) of motion surgery compared with patients with distance ratios <1.25. Median femoral spike area ratios were similar between the case (0.2; IQR, 0.1–0.5) and control (0.2; IQR, 0.0–0.5) groups and were not associated with increased odds of motion surgery (P = 0.34).

Conclusions:

A larger spike distance ratio is associated with increased odds of subsequent motion surgery.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
The Impact of Posterior Spinal Fusion (PSF) on Coronal Balance in Adolescent Idiopathic Scoliosis (AIS): A New Classification and Trends in the Postoperative Period
Authors: Anari Jason B. , Tatad Aaron , Cahill Patrick J. , Flynn John M.
Published: July 2020

Introduction:

One of the primary goals of scoliosis surgery is to balance the head over the pelvis (or avoid creating imbalance). Historically, a normal coronal balance was defined as the C7 plumb line (C7PL) within 2 cm of the central sacral vertical line (CSVL); however, there is limited published information regarding the speed/magnitude and success/failure of balancing, rebalancing, or unbalancing in the postoperative period. The purpose of this study is to classify and quantify coronal plane balance postoperatively in adolescent idiopathic scoliosis when using pedicle screw instrumentation.

Methods:

Evaluated patients with adolescent idiopathic scoliosis who had a posterior spinal fusion withstanding 2-view, posteroanterior and lateral radiographs of the entire spine performed at first erect visit, 6, 12, and 24 months. To measure coronal balance, a C7PL was measured and compared with the CSVL. A negative value denotes the leftward deviation of the C7PL and a positive value a rightward deviation. The authors then created a novel coronal balance classification system.

Results:

A total of 954 patients met the inclusion criteria. There was a strong trend toward improving coronal balance, especially between first erect and 6 months; the proportion of out of balance patients declined throughout the 2-year period: preoperative 372 of 954 (39%), first erect 297 of 954 (31.1%), 6 months 167 of 954 (17.5%), 1 year 136 of 954 (14.3%), and 2 years 115 of 954 (12.0%). Analyzing the patients most out of balance immediately after posterior spinal fusion, 35 of 50 (70%) in group 3 regained balance by 2 years. Out of the remaining 15 patients, 12 corrected to group 1 (24%), 2 patients to group 2 (4%), and 1 patient remained in group 3 (2%).

Conclusions:

This large, longitudinal postoperative study of coronal balance documents a strong trend toward postoperative rebalancing, with the largest gains between first erect image and 6 months. The 31% of patients out of balance at first erect declined to only 12.1% at 2 years.
Rethinking the Approach to Continuing Professional Development Conferences in the Era of COVID-19
Authors: Gottlieb Michael , Egan Daniel J. , Krzyzaniak Sara M. , Wagner Jason , Weizberg Moshe , Chan Teresa
Published: July 2020

The COVID-19 pandemic has required a substantial change to the approach used for traditional, in-person continuing professional development (CPD) conferences. Running a virtual CPD conference will necessitate consideration of digital platforms and conversion of large group and small group sessions, abstract presentations, and networking events to a digital medium. This paper will discuss these challenges and present strategies to address them for CPD conference planning in the era of COVID-19.
Extended Thromboprophylaxis With Betrixaban or Rivaroxaban for Acutely Ill Hospitalized Medical Patients: Meta-Analysis of Prespecified Subgroups
Authors: Jamil Adeel , Jamil Umer , Singh Kamaldeep , Khan Faris , Chi Gerald
Published: July 2020

Background:

Betrixaban and rivaroxaban are the direct anticoagulants approved in the United States for extended venous thromboembolism (VTE) prophylaxis among acutely ill medical patients. The efficacy and safety in specific subgroups remain unclear.

Methods:

A meta-analysis of 3 randomized trials involving extended thromboprophylaxis with betrixaban or rivaroxaban versus enoxaparin for medically ill patients was performed to compare VTE (composite of asymptomatic proximal and symptomatic deep vein thrombosis, pulmonary embolism, or VTE-related death) and major bleeding in subgroups by baseline D-dimer, age, sex, and major medical illness on hospitalization. Risk difference (RD) was computed with the Mantel-Haenszel method by fitting a fixed-effect model. Heterogeneity of treatment effect across subgroups was examined using the nominal thresholds of P < 0.05 and I2 > 75%.

Results:

Compared with enoxaparin, extended betrixaban or rivaroxaban reduced VTE (RD = –1.51% [95% CI, –2.32% to –0.69%]; P = 0.0003) without excess major bleeding (RD = 0.12% [–0.05% to 0.29%]; P = 0.16). A significant effect modification was observed in the subgroups by D-dimer (P = 0.004) and age (P = 0.04). Patients with D-dimer >2× upper limit of normal (ULN) experienced a greater VTE reduction (RD = –2.39% [–3.57% to –1.21%]; P < 0.0001) than those with ≤2×ULN (RD = –0.26% [–1.08% to 0.56%]; P = 0.53). Similarly, patients aged ≥75 years had a greater VTE reduction (RD = –2.29% [–3.49% to –1.09%]; P = 0.0002) than those aged <75 years (RD = –0.63% [–1.70% to 0.44%]; P = 0.25). Treatment effect was consistent across the remaining subgroups.

Conclusions:

A more favorable efficacy and comparable safety outcome associated with extended betrixaban or rivaroxaban were observed among medical inpatients with D-dimer >2×ULN or aged ≥75 years. D-dimer and advanced age may assist in decision-making on pharmacological thromboprophylaxis for hospitalized medical patients.
Big data requirements for artificial intelligence
Authors: Wang Sophia Y. , Pershing Suzann , Lee Aaron Y.
Published: July 2020

Purpose of review

To summarize how big data and artificial intelligence technologies have evolved, their current state, and next steps to enable future generations of artificial intelligence for ophthalmology.

Recent findings

Big data in health care is ever increasing in volume and variety, enabled by the widespread adoption of electronic health records (EHRs) and standards for health data information exchange, such as Digital Imaging and Communications in Medicine and Fast Healthcare Interoperability Resources. Simultaneously, the development of powerful cloud-based storage and computing architectures supports a fertile environment for big data and artificial intelligence in health care. The high volume and velocity of imaging and structured data in ophthalmology and is one of the reasons why ophthalmology is at the forefront of artificial intelligence research. Still needed are consensus labeling conventions for performing supervised learning on big data, promotion of data sharing and reuse, standards for sharing artificial intelligence model architectures, and access to artificial intelligence models through open application program interfaces (APIs).

Future requirements for big data and artificial intelligence include fostering reproducible science, continuing open innovation, and supporting the clinical use of artificial intelligence by promoting standards for data labels, data sharing, artificial intelligence model architecture sharing, and accessible code and APIs.
Comparison of Peripapillary Retinal Nerve Fiber Layer Thickness, Functional Subzones, and Macular Ganglion Cell-Inner Plexiform Layer in Differentiating Patients With Mild, Moderate, and Severe Open-angle Glaucoma
Authors: Huo Yan Jiao , Thomas Ravi , Li Lei , Cao Kai , Wang Huai Zhou , Wang Ning Li
Published: July 2020

Précis:

Based on 6 functional subzones of peripapillary retinal nerve fiber layer (pRNFL) thickness, the glaucoma detection ability of zone 2 and zone 4 was high and comparable with that of mean pRNFL in glaucoma groups.

Purpose:

To compare diagnostic performance of pRNFL subzones, mean pRNFL thickness, and macular ganglion cell-inner plexiform layer (mGCIPL) in mild, moderate, and severe open-angle glaucoma.

Materials and Methods:

One hundred eighty-one patients with open-angle glaucoma (318 eyes: 122 mild, 60 moderate, and 136 severe glaucoma) and 70 normal subjects underwent spectral-domain optical coherence tomography measurements. FORUM software was used to determine subzone pRNFL thickness mapping the visual field to the optic disc (6 zones). The thickness and area under the receiver operating curve (AUROC) of each parameter were compared between groups. DeLong’s method was used to compare AUROCs between mean pRNFL and mGCIPL and each zone of spectral-domain optical coherence tomography parameters.

Results:

Mean pRNFL thickness (99.81±10.06 μm) and mGCIPL thickness (83.24±5.91 μm) were higher in controls compared with glaucoma (67.42±13.22 and 63.31±10.85 μm; P<0.001). Mean pRNFL had the best diagnostic performance in mild (0.957) and severe (1.000) glaucoma. Of the 6 zonal parameters, zone 2 (associated with the inferior temporal sector) best discriminated glaucomatous changes between controls and mild and moderate (0.941 and 0.988). Zone 4 (associated with the superior temporal sector) best discriminated glaucomatous changes between controls and severe glaucoma (0.998). AUROCs for zone 2 and zone 4 were not significantly different from mean pRNFL and mGCIPL in all glaucoma groups (all P>0.0038).

Conclusions:

Mean pRNFL had the best diagnostic performance in mild and severe glaucoma. Glaucoma detection ability of zone 2 and zone 4 was high and comparable with that of mean pRNFL and mGCIPL in all glaucoma groups.
Proline-assisted Tube Insertion Through Sulcus in Ahmed Valve
Authors: Kasuga Toshimitsu , Asaoka Satoko , Asada Yosuke , Iwamoto Satoshi , Hirakata Toshiaki , Honda Rio , Ohta Toshihiko , Matsuda Akira
Published: July 2020

To prevent corneal endothelial cell loss, ciliary sulcus tube insertion is preferred for the pseudophakic eye. However, we sometimes encounter technical difficulties when inserting the tube through the sulcus. Even in cases in which we are able to insert a 23-G needle through the sulcus into the space between the iris and intraocular lens, the tube of Ahmed valve may stray into the vitreous cavity or under Elschnig pearls. To remedy such conditions, we developed a new tube insertion method using a 4-0 proline stent as a guide to insert the tube in the appropriate position.
Offset analgesia identifies impaired endogenous pain modulation in pediatric chronic pain disorders
Authors: Shulman Julie , Zurakowski David , Keysor Julie , Jervis Kelsey , Sethna Navil F.
Published: July 2020

Offset analgesia (OA), a psychophysical test of endogenous pain inhibition, is diminished in many adult chronic pain disorders but OA has not been investigated in youth with chronic pain disorders. This study assessed OA responses in 30 youth with chronic primary and secondary pain disorders and 32 healthy controls. The OA, control, and constant thermal tests were evoked with an individualized noxious heat stimulus of approximately 50/100 mm on a visual analogue scale followed by 1°C offset temperature. This study also examined the association of OA responses with 2 self-report measures of pain sensitivity, the Central Sensitization Inventory (CSI) and Pain Sensitivity Questionnaire. Patients exhibited diminished capacity to activate OA with a reduction in ΔeVASc of 53 ± 29% vs controls 74 ± 24% (P = 0.003) even after multivariate regression adjusting for age, sex, and body mass index. Patients also showed decreased ability to habituate to a constant noxious heat stimulus compared to controls (P = 0.021). Central Sensitization Inventory scores showed excellent predictive accuracy in differentiating patients from controls (area under the curve = 0.95; 95% CI: 0.91-0.99) and CSI score ≥30 was identified as an optimal cutoff value. Pain Sensitivity Questionnaire scores did not differentiate patients from controls nor correlate with OA. In this study, 60% of youth with chronic pain showed reduced capacity for endogenous pain inhibition.
Assessing Physician Adherence to Guidelines for CervicalCancer Screening and Management of AbnormalScreening Results
Authors: Min Caroline J. , Massad L. Stewart , Dick Rebecca , Powell Matthew A. , Kuroki Lindsay M.
Published: July 2020

Objective

The aim of the study was to survey obstetrician-gynecologists' cervical cancer screening practices and management of cervical abnormalities to ascertain adherence to guidelines.

Methods

From January to July 2019, obstetrician-gynecologists at 5 St. Louis area hospitals were surveyed online about cervical cancer screening and management practices through 13 clinical vignettes. Survey scores and the American Society of Colposcopy and Cervical Pathology (ASCCP) app use were compared using Mann-Whitney tests.

Results

When screening 30- to 65-year-old participants, 114 (98%) of the 116 total participants used co-testing, but only 71 (61%) screened at 5-year intervals. None used primary human papillomavirus (HPV) testing. For 21- to 29-year-old participants, 17 (15%) screened with annual cytology, whereas 14 (12%) used annual or every 3-year co-testing. Forty eight (41%) screened younger than 21 years, regardless of risk factors or only if immunocompromised. Eleven (9%) continued screening after total hysterectomy for benign indications. Only 2 (2%) responded to all clinical vignettes in adherence to guidelines. More than 30% of participants would pursue unnecessary HPV testing and/or loop electrosurgical excision procedure for persistent low-grade cytology. Fifty eight (48%) incorrectly reported hysterectomy as management for adenocarcinoma in situ on biopsy. Participants would undertreat young women with high-grade abnormalities including high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia 3 (48, 41%) and high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia 1 (65, 56%). Forty one (35%) reported exiting women from screening prematurely. The median score for participants using the ASCCP app was significantly greater than those who did not (79% vs 71%, p = .002).

Conclusions

Midwestern obstetrician-gynecologists' adherence to the guidelines for cervical cancer screening and management of abnormal results is suboptimal. Although co-testing for women aged 30–65 years has been broadly adopted, primary HPV testing has not. Physicians overscreen, overtreat low-grade lesions, and undertreat high-grade lesions in young women.
Breathing Life Back Into the Kidney—Continuous Renal Replacement Therapy and Veno-Venous Extracorporeal Membrane Oxygenation
Authors: Deatrick Kristopher B. , Mazzeffi Michael A. , Galvagno Samuel M. , Boswell Kimberly , Kaczoroswki David J. , Rabinowitz Ronald P. , Madathil Ronson J. , Cornachione Christopher R. , Herr Daniel L. , Scalea Thomas M. , Menaker Jay
Published: July 2020

The purpose of this study was to evaluate the incidence of continuous renal replacement therapy (CRRT) in patients supported with veno-venous extracorporeal membrane oxygenation (VV ECMO). Secondary outcomes included mortality and the need for hemodialysis on hospital discharge. We performed a retrospective cohort study of all patients admitted to a specialty unit on VV ECMO between August 2014 and August 2018. Trauma and bridge to lung transplant patients were excluded. Demographics, comorbidities, pre-ECMO, ECMO, and renal replacement therapy outcome data were collected and analyzed with parametric and nonparametric statistics as appropriate. One hundred eighty-seven patients were enrolled. Median age was 45 (32, 55) years; precannulation pH, 7.21 (7.12, 7.30); PaO2/FiO2 ratio, 69 (56, 86); respiratory ECMO survival prediction score, 3 (0, 5); sequential organ failure assessment score, 12 (10, 14); and creatinine, 1.45 (0.93, 2.35) mg/dL. Overall survival to hospital discharge was 74.6%. Ninety-four (50.3%) patients had CRRT while on VV ECMO. Median time on CRRT was 14 (7, 21) days with 59 (61.4%) of these patients surviving to hospital discharge. Four (6.8%) patients, none with documented preexisting renal disease, required hemodialysis on discharge. CRRT patients had a statistically higher precannulation sequential organ failure assessment score, creatinine, total bilirubin and lower precannulation pH, respiratory ECMO survival prediction score, and platelet count compared with non-CRRT patients. Survival was 61.4% vs. 88.1% (p < 0.001). More than half of our patients received CRRT while on VV ECMO. CRRT was used in a more critically ill patient population and was associated with higher in-hospital mortality. However, for patients who survived to hospital discharge, the majority have full renal recovery.
Risk of recurrent venous thromboembolism related to prior risk situations: re-evaluation of a cohort study with a longer follow-up
Authors: Xavier e Silva Camila , Ribeiro Daniel D. , Lijfering Willem M. , Azevedo Paula Duarte Gonçalves Guimarães , de Castro Brommonschenkel Christina , Torres Maíra Soares , Rosendaal Frits R. , Rezende Suely M.
Published: July 2020

Venous thromboembolism (VTE) is a chronic disease. Strategies to assess groups at a high risk of recurrence are needed. We reported that patients without prior risk situation for VTE had an incidence rate ratio (IRR) three times higher when compared with those with this history. The aim of this study was to re-evaluate the cohort, with a longer follow-up and evaluated the association between the absence of a prior risk situation for VTE with an increased risk for recurrence. A total of 289 patients with a previous VTE were followed for 116 months. Patients were advised to attend the outpatients’ clinic in case of suspected VTE recurrence. Incidence rates of recurrent thrombotic events were calculated as the number of events over the accumulated observation time. Recurrent VTE occurred in 52 (18%) patients. Patients with a provoked first event and positive prior risk situations for VTE had an incidence rate for recurrence of 1.2 [95% confidence interval (95% CI), 0.7–1.9] per 100 patient-years. The IRR of this subgroup compared with patients with a provoked event without prior risk situations for VTE was 0.9 (95% CI 0.4–2.4). IRR was 2.5 (95% CI, 1.3–4.9) in patients with an unprovoked event and positive prior risk situations and 5.9 (95% CI, 32.8–12.5) in patients with an unprovoked event and no prior risk situations compared with patients with a provoked event without other prior risk situations for VTE. Exposure to prior risk situations for VTE was a protective factor among those patients whose first VTE event was unprovoked.
Two novel pathogenic variants in KIAA1109 causing Alkuraya-Kučinskas syndrome in two Czech Roma brothers
Authors: Meszarosova Anna Uhrova , Lastuvkova Jana , Rennerova Ladislava , Hitka Patrik , Cihlar Filip , Seeman Pavel , Safka Brozkova Dana
Published: July 2020

Recently described Alkuraya-Kučinskas syndrome (ALKKUCS) clinically presented with severe congenital hydrocephalus, severe brain hypoplasia and other multiple malformations has been described in only few families worldwide to date. ALKKUCS is caused by biallelic pathogenic variants in the KIAA1109 gene with autosomal recessive inheritance. We describe two brothers of Roma origin born with severe congenital hydrocephalus, brain hypoplasia and other clinical findings corresponding with ALKKUCS. Using WES two novel pathogenic variants c.359-1G>A and c.14564_14565del in compound heterozygous status in the KIAA1109 gene were found in both brothers. We consider that the number of healthy heterozygous carriers of pathogenic variants in KIAA1109 could be higher than it is known and pathogenic variants in KIAA1109 could be more frequent cause of congenital hydrocephalus and severe brain dysplasias.
Pulmonary arterial hypertension: closing the gap in congenital heart disease
Authors: Brida Margarita , Nashat Heba , Gatzoulis Michael A.
Published: July 2020

Purpose of review

Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a common association adversely affecting quality of life and survival in these patients. We provide herewith recent advances in the understanding and management of PAH-CHD.

Recent findings

Significant progress has been made in disease-targeting therapy with pulmonary vasodilators for the treatment of Eisenmenger syndrome, the most severe form of PAH-CHD. Important gaps, however, still exist in the assessment and management of patients with PAH-CHD with systemic to pulmonary shunts. The choice of therapy, either interventional, medical, or both is an on-going dilemma that requires more long-term data. PAH after defect closure represents the most concerning subgroup of patients with the worst prognosis, requiring close follow-up and proactive disease-targeting therapy treatment. Small defects are not considered responsible for patients who have severe PAH and therefore, present different subgroup of patients similar to idiopathic PAH.

Even with advances in diagnosis and treatment PAH-CHD remains a challenging field requiring lifelong follow-up and meticulous treatment in centres specialized in both CHD and PAH.
Early detection of pancreatic cancer
Authors: Garg Sushil Kumar , Chari Suresh T.
Published: July 2020

Purpose of review

Pancreatic cancer is the third leading cause of cancer death and with a dismal 5-year survival of 10%. Poor survival of pancreatic cancer is mostly due to its presentation and diagnosis at a late stage. The present article aims to update clinicians with recent progress in the field of early detection of pancreatic cancer.

Recent findings

Pancreatic cancer screening is not recommended in the general population due to its low prevalence. In this review, we discuss high-risk groups for pancreatic cancer, including inherited predisposition to pancreatic cancer, new-onset diabetes, mucinous pancreatic cyst, and chronic pancreatitis. We discuss methods of enrichment of high-risk groups with clinical models using electronic health records and biomarkers. We also discuss improvements in imaging modalities and emerging role of machine learning and artificial intelligence in the field of imaging and biomarker to aid in early identification of pancreatic cancer.

There are still vast challenges in the field of early detection of pancreatic cancer. We need to develop noninvasive prediagnostic validated biomarkers for longitudinal surveillance of high-risk individuals and imaging modalities that can identify pancreatic cancer early.
A Single-Institution Experience of Induction 5-Fluorouracil, Leucovorin, Irinotecan, and Oxaliplatin Followed by Surgery Versus Consolidative Radiation for Borderline and Locally Advanced Unresectable Pancreatic Cancer
Authors: Cecchini Michael , Miccio Joseph A. , Pahade Jay , Lacy Jill , Salem Ronald R. , Johnson Skyler B. , Blakaj Adriana , Stein Stacey , Kortmansky Jeremy S. , Johung Kimberly L.
Published: July 2020

Objectives

In the 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) era, the benefit of surgery versus definitive radiation for borderline resectable (BR) and locally advanced (LA) unresectable pancreatic ductal adenocarcinoma (PDAC) is not well defined. Our primary objective was to identify the survival impact of surgery for BR and LA unresectable PDAC treated with induction FOLFIRINOX.

Methods

We performed a single-center retrospective review of BR and LA PDAC treated with FOLFIRINOX from 2010 to 2018. The overall survival of surgery and consolidative radiotherapy was estimated in the Kaplan-Meier method and compared via the log-rank test. Subgroup analyses were conducted for BR and LA patients.

Results

We identified 101 BR and LA PDAC patients treated with induction FOLFIRINOX (41 surgeries and 60 consolidative radiotherapies). Surgery patients were 68.3% (28/41) BR and 31.7% (13/41) LA, whereas consolidative radiotherapy patients were 30% (18/60) BR and 70% (42/60) LA. The R0 resection rate was 100%, and 46.3% (19/41) received preoperative radiation. Median overall survival of surgery versus consolidative radiotherapy was 42.3 versus 19.6 months, respectively (P < 0.001). On multivariate analysis, surgery associated with improved survival.

Conclusions

Surgery after induction FOLFIRINOX is feasible and has a clinically meaningful survival benefit in BR and LA PDAC.