bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Situ Pulmonary Thrombolysis and Perfusion Lung Angiography in Severe COVID-19 Respiratory Failure
Authors: Pérez-Calatayud Angel Augusto , Enriquez-García Rocío , Fareli-González Christian , Barrett Christopher D. , Saldivar-Rodea Carlos Alberto , Perulles-Marin Jorge , Reyes-Caldelas Miguel Angel , Rosenberg-Contreras Carlos Ivan , Gómez-Moreno Julieta Berenice , Guerrero-Avendaño Guadalupe , Serrano-Loyola Raúl , Carrillo-Esper Raúl , Moore Ernest E. 
Published: March 2022

OBJECTIVES:
A proof-of-concept study using thrombolysis with catheter-directed tissue plasminogen activator (tPA) and pulmonary angiography imaging was performed to visualize perfusion deficits and reperfusion/therapeutic effects of tPA.

DESIGN:
A prospective, open-label, compassionate study. Descriptive statistics were presented for categorical variables and as means with sds for continuous variables. The Wilcoxon test was used to determine the differences between the two-related samples and a t test for continuous variables. Statistical significance was set at p value of less than 0.05. Agreement between observations was evaluated using the Kappa Cohen index and overall agreement using the Fleiss Kappa coefficient.

SETTING:
A single COVID-19 ICU of Mexico´s General Hospital Dr Eduardo Liceaga.

SUBJECTS:
Fifteen patients with severe Delta variant severe acute respiratory syndrome coronavirus 2 infection, 18–75 years old, requiring mechanical ventilation with a persistent Fio
2 requirement of 70% or higher and Pao
2/Fio
2 ratio (or imputed ratio) less than 150 for more than 4 hours. The coagulation inclusion criteria were International Society on Thrombosis and Haemostasis score greater than 5, and presence of a d-dimer greater than 1,200, with viscoelastic testing using rotational thromboelastometry (Instrumentation Laboratories, Mexico City, Mexico) showing both hypercoagulability (EXTEM amplitude at 5 min > 65 FIBTEM > 30) and hypofibrinolysis (EXTEM maximum lysis < 8%).

INTERVENTIONS:
Catheter-directed tPA angiography and iFlow system analysis to assess pre-tPA baseline pulmonary perfusion and changes in response to thrombolysis.

RESULTS:
Nine patients had microvascular filling defects demonstrated by angiography, and good agreement was found with iFlow analysis (ƙ = 0.714). Statistically significant differences were identified in the area under the curve (AUC) region of interest/AUC reference tissue with and without filling defects in phase 2 DM –0.09206 (sd ± 0.16684) (p = 0.003). The Pao
2/Fio
2 values measured immediately and 48 hours after the procedure were significantly higher (p = 0.001 and p = 0.005, respectively). Statistically significant differences were found in d-dimer values (p = 0.007), Fio
2 (p = 0.002), and oxygen saturation in arterial blood/Fio
2 (p = 0.045), as well as in the number of patients who required prone positioning before, immediately after the procedure, and at 48 hours after the procedure (p = 0.002).

CONCLUSIONS:
Thrombolysis with catheter-directed tPA resulted in imaging evidence via pulmonary angiography and iFlow technology of improved lung perfusion in COVID-19 patients with severe respiratory failure.
COVID-19 Patients Require Prolonged Extracorporeal Membrane Oxygenation Support for Survival Compared With Non-COVID-19 Patients
Authors: Russ Martin , Menk Mario , Graw Jan Adriaan , Skrypnikov Vladimir , Hunsicker Oliver , Rudat Kathleen , Weber-Carstens Steffen , Francis Roland C. E. , Pickerodt Philipp A. 
Published: March 2022

OBJECTIVES:
To investigate the ICU survival of venovenous extracorporeal membrane oxygenation (ECMO) patients suffering from COVID-19–related acute respiratory distress syndrome (ARDS) versus ECMO patients without COVID-19 (non-COVID-19)–related ARDS.

DESIGN:
Preliminary analysis of data from two prospective ECMO trials and retrospective analysis of a cohort of ARDS ECMO patients.

SETTING:
Single-center ICU.

PATIENTS:
Adult ARDS ECMO patients, 16 COVID-19 versus 23 non-COVID-19 patients. Analysis of retrospective data from 346 adult ARDS ECMO patients.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
COVID-19 and non-COVID-19 ARDS patients did not differ with respect to preexisting disease or body mass index. ICU survival rate was 62% for COVID-19 ECMO patients and 70% for non-COVID-19 ECMO patients. COVID-19 ECMO survivors were supported with ECMO for a median of 43 days (interquartile range [IQR], 18–58 d) versus 16 days (IQR, 19–39 d; p = 0.03) for non-COVID-19 patients. The median duration of ECMO therapy for all ARDS patients between 2007 and 2018 was 15 days (IQR, 6–28 d). The subgroup of patients suffering from any viral pneumonia received ECMO support for a median of 16 days (IQR, 9–27 d), survivors of influenza pneumonia received ECMO support for 13 days (IQR, 7–25 d).

CONCLUSIONS:
COVID-19 patients required significant longer ECMO support compared with patients without COVID-19 to achieve successful ECMO weaning and ICU survival.
Twenty-Two–Year Clinical Outcome of a Case of Endokeratoplasty
Authors: Gunasekera Chrishan Duminda , Yu Angeli Christy , Busin Massimo 
Published: March 2022

Purpose:
The purpose of this study was to report the 22-year clinical outcome of a patient who underwent endokeratoplasty.

Methods:
To report the clinical outcomes of 37-year-old male who underwent endokeratoplasty for decompensated Fuchs endothelial dystrophy in 1998.

Results:
After subsequent cataract surgery and iridoplasty, at 22 years post endokeratoplasty, the Snellen best spectacle-corrected visual acuity is 20/20 (−5.50 sphere −3.00 cylinder at 135 degrees), endothelial cell count is 645 cells/mm2, central corneal thickness is 644 μm, and the cornea remains clear with no evidence of graft rejection or failure.

Conclusions:
To the best of our knowledge, this is the longest reported outcome for selective endothelial replacement. The patient undergoing endokeratoplasty can achieve an excellent visual acuity and long-term graft survival.
Corneal Cellular and Neuroinflammatory Changes After SARS-CoV-2 Infection
Authors: Kolkedi Zsofia , Csutak Adrienne , Szalai Eszter 
Published: March 2022

Purpose:
The purpose of this study was to evaluate corneal cellular and ultrastructural changes and to quantify the neuroinflammatory process in patients after mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods:
Thirty patients after SARS-CoV-2 infection and 41 age-matched controls were examined. All subjects underwent in vivo confocal microscopy of the corneal cell layers and subbasal nerve fibers with the Heidelberg Retina Tomograph II. Semiautomated analysis of basal epithelial, anterior and posterior stromal keratocyte, and endothelial cell density was performed. Dendritic cell (DC) density and area were also calculated, and subbasal nerve plexus morphology was analyzed.

Results:
The posterior stromal keratocyte density was significantly lower in patients after SARS-CoV-2 infection (P = 0.0006). DC density in the central cornea was significantly higher in patients after SARS-CoV-2 infection (P = 0.0004). There was a significant difference in the DC area between the 2 groups (P < 0.0001). Significantly altered subbasal nerve fiber morphology was detected in patients after SARS-CoV-2 infection compared with healthy volunteers (P < 0.05).

Conclusions:
Corneal cellular and ultrastructural changes demonstrated in this study suggest neuroinflammatory consequences of COVID-19 in the cornea in the absence of ophthalmoscopic alterations.
Preexisting Mental Health Illness Among Victims of Sexual Assault: Case Studies to Inform Sexual Assault Nurse Examiner Practice
Authors: Scott Tilley Donna , Edwards Carrie , Richmond Misty , Stunkard Kimberly 
Published: March 2022

ABSTRACT

Background
Sexual assault is a pervasive problem associated with negative long- and short-term consequences related to mental health consequences, educational function, physical health, and sexual and relationship functioning. People with mental illness, particularly those with psychotic disorders, have a significantly higher risk of becoming victims of violence compared with the general population.

Methods
Three case studies of women with preexisting mental health problems who were sexually assaulted and requested a sexual assault examination are presented. These cases illustrate common mental health problems, how mental health problems can be associated with an increased risk for sexual assault, and things the sexual assault nurse examiner (SANE) should consider in the care and treatment of these patients.

Results
These cases illustrate important ideas regarding the care of people who have been sexually assaulted: prioritizing safety, ethical issues related to consent, the importance of empathetic communication, and the need for SANEs to expand their knowledge to improve care of patients with mental health disorders.

Discussion
Being sexually assaulted can contribute to destabilization, prolongation, and exacerbation of existing mental illness, placing patients at an increased risk for sexual assault, beginning a vicious cycle of mental illness and violence. Working effectively with the interdisciplinary team, the SANE can help break this devastating cycle of violence.
Prospective Pilot Study of Robotic-Assisted Harvest of the Latissimus Dorsi Muscle: A 510(k) Approval Study with U.S. Food and Drug Administration Investigational Device Exemption
Authors: Shuck John , Asaad Malke , Liu Jun , Clemens Mark W. , Selber Jesse C. 
Published: March 2022

Background:
There are no U.S. Food and Drug Administration (FDA)–approved indications for robotic plastic surgery. This study was designed to demonstrate safety and efficacy of the robotic latissimus dorsi harvest for FDA approval.

Methods:
This prospective, single-arm study was conducted under an investigational device exemption through the FDA for obtaining 510(k) approval. The primary safety endpoint was adverse events attributable to harvest. Primary efficacy endpoints included muscle viability after harvest and conversion to open technique. Secondary endpoints included postoperative pain and upper extremity function.

Results:
Fifteen patients enrolled, with a mean age of 50 ± 10 years and a mean body mass index of 25 ± 4 kg/m2. There were no adverse events, all muscles were viable after harvest, and there were zero conversions to open procedures. Visual analogue scale scores for pain progressively decreased postoperatively and returned to baseline, indicating resolution of postoperative pain. Physical therapy assessment demonstrated recovery of function in all range-of-movement domains by 36 weeks. There was no difference in function of the operated extremity between baseline and 36 weeks’ follow-up for Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire (p = 0.87); QuickDASH Work Module (p > 0.05); and QuickDASH Sports Module (p > 0.05).

Conclusions:
The use of the da Vinci Robotic Surgical System is safe based on zero adverse events attributable to harvest and efficacious based on 100 percent muscle viability after harvest and zero conversions to open technique. There appears to be little to no long-term functional deficit or pain from muscle harvest. Given these results and their own prestudy guidelines, the robotic latissimus dorsi qualifies for 510(k) submission by Intuitive Surgical and approval by the U.S. FDA.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Surgical Treatment of Granulomatous Breast Deformities Caused by Injection of Foreign Substances in Transgender Women: A Case Series and Algorithm
Authors: Cordero Daniella M. , Srinivasa Dhivya , Barnes Laura L. , Ray Edward , Terry Michael J. 
Published: March 2022

Summary:
Despite potentially devastating complications, free foreign substance injections for feminizing breast augmentation remain common among transgender women. To date, the literature regarding surgical treatment of these deformities among transgender women remains limited. The authors present a case series of transgender women presenting for surgical management of granulomatous breast deformities secondary to free foreign substance injections between January of 2016 and February of 2020. Seven transgender women presented for surgical management of complications secondary to free foreign substance injections of the breast. These patients ranged in age from 29 to 53 years, all identified as Hispanic/Latinx, and five were primarily Spanish speakers. All were recipients of public insurance. Six of the seven patients received free foreign substance injections outside of the United States, with an average time from initial injections to presentation of 19.3 ± 15.7 years. Three patients presented with a history of prior revisions by other surgeons. Four underwent staged reconstruction at the authors’ institutions. Patients were followed for, on average, 10.7 ± 12.6 months after their initial surgery. There were no major complications. The most common minor complication was delayed wound healing. In the present series, the authors illustrate that, with careful consideration and patient selection, it is possible to perform safe and successful breast reconstruction for the management of foreign substance granulomas in transgender women. They also provide an algorithm based on patient-specific factors to guide treatment decisions in this patient population. Further research is needed to determine the generalizability and applicability of this algorithm.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Changes in both top-down and bottom-up effective connectivity drive visual hallucinations in Parkinson’s disease
Authors: Thomas George EC , Zeidman Peter , Sultana Tajwar , Zarkali Angeliki , Razi Adeel , Weil Rimona S 
Published: March 2022

ABSTRACTVisual hallucinations are common in Parkinson’s disease and are associated with poorer quality of life and higher risk of dementia. An important and influential model that is widely accepted as an explanation for the mechanism of visual hallucinations in Parkinson’s disease and other Lewy-body diseases is that these arise due to aberrant hierarchical processing, with impaired bottom-up integration of sensory information and overweighting of top-down perceptual priors within the visual system. This hypothesis has been driven by behavioural data and supported indirectly by observations derived from regional activation and correlational measures using neuroimaging. However, until now, there was no evidence from neuroimaging for differences in causal influences between brain regions measured in patients with Parkinson’s hallucinations. This is in part because previous resting-state studies focus on functional connectivity, which is inherently undirected in nature and cannot test hypotheses about directionality of connectivity. Spectral dynamic causal modelling is a Bayesian framework that allows the inference of effective connectivity – defined as the directed (causal) influence that one region exerts on another region – from resting-state functional MRI data. In the current study, we utilise spectral dynamic causal modelling to estimate effective connectivity within the resting-state visual network in our cohort of 15 Parkinson’s disease visual hallucinators, and 75 Parkinson’s disease non-hallucinators. We find that visual hallucinators display decreased bottom-up effective connectivity from the lateral geniculate nucleus to primary visual cortex and increased top-down effective connectivity from left prefrontal cortex to primary visual cortex and medial thalamus, as compared to non-hallucinators. Importantly, we find that the pattern of effective connectivity is predictive of the presence of visual hallucinations and associated with their severity within the hallucinating group. This is the first study to provide evidence, using resting state effective connectivity, to support a model of aberrant hierarchical predictive processing as the mechanism for visual hallucinations in Parkinson’s disease.
Nanobubbles are Non-Echogenic for Fundamental-Mode Contrast-Enhanced Ultrasound Imaging
Authors: Myers John Z. , Navarro-Becerra J. Angel , Borden Mark A. 
Published: March 2022

AbstractMicrobubbles (1–10 µm diameter) have been used as conventional ultrasound contrast agents (UCAs) for applications in contrast-enhanced ultrasound (CEUS) imaging. Nanobubbles (<1 µm diameter) have recently been proposed as potential extravascular UCAs that can extravasate from the leaky vasculature of tumors or sites of inflammation. However, the echogenicity of nanobubbles for CEUS remains controversial owing to prior studies that have shown very low ultrasound backscatter. We hypothesize that microbubble contamination in nanobubble formulations may explain the discrepancy. To test our hypothesis, we examined the size distributions of lipid-coated nanobubble and microbubble suspensions using multiple sizing techniques, examined their echogenicity in an agar phantom with fundamental-mode CEUS at 7 MHz and 330 kPa peak negative pressure, and interpreted our results with simulations of the modified Rayleigh-Plesset model. We found that nanobubble formulations contained a small contamination of microbubbles. Once the contribution from these microbubbles is removed from the acoustic backscatter, the acoustic contrast of the nanobubbles was shown to be near noise levels. This result indicates that nanobubbles have limited utility as UCAs for CEUS.
Characterization of prefusion-F-specific antibodies elicited by natural infection with human metapneumovirus
Authors: Rush Scott A. , Brar Gurpreet , Hsieh Ching-Lin , Chautard Emilie , Rainho-Tomko Jennifer N. , Slade Chris , Bricault Christine A. , Kume Ana , Kearns James , Groppo Rachel , Mundle Sophia , Zhang Linong , Casimiro Danilo , Fu Tong-Ming , DiNapoli Joshua M. , McLellan Jason S. 
Published: March 2022

ABSTRACTHuman metapneumovirus (hMPV) is a major cause of acute respiratory tract infections in infants and the elderly for which there are no approved vaccines or antibody therapies. The viral fusion (F) glycoprotein is required for entry and is the primary target of neutralizing antibodies, however, little is known about the humoral immune response generated by humans as a result of natural infection. Here, we use stabilized hMPV F proteins to interrogate memory B cells from two elderly donors. We obtained over 700 paired non-IgM antibody sequences representing 563 clonotypes, indicative of a highly polyclonal antibody response to hMPV F in these individuals. Characterization of 136 of these monoclonal antibodies revealed broad recognition of the hMPV F surface, with potent neutralizing antibodies targeting each antigenic site. Cryo-EM structures of two neutralizing antibodies reveal the molecular basis for recognition of two prefusion-specific epitopes at the membrane-distal apex of hMPV F. Collectively these results provide new insights into the humoral response to hMPV infection in the elderly and will guide development of novel vaccine antigens.
Zfp503/Nlz2 is Required for RPE Differentiation and Optic Fissure Closure
Authors: Boobalan Elangovan , Thompson Amy H. , Alur Ramakrishna P. , McGaughey David , Dong Lijin , Shih Grace , Vieta-Ferrer Emile R. , Onojafe Ighovie F. , Kalaskar Vijay K. , Arno Gavin , Lotery Andrew J. , Guan Bin , Bender Chelsea , Memon Omar , Brinster Lauren , Soleilhavoup Clement , Panman Lia , Badea Tudor C. , Minella Andrea , Lopez Antonio Jacobo , Thomasy Sara , Moshiri Ala ,   Genomics England Research Consortium, Blain Delphine , Hufnagel Robert B. , Cogliati Tiziana , Bharti Kapil , Brooks Brian P. 
Published: March 2022

AbstractPurposeUveal coloboma is a congenital eye malformation caused by failure of the optic fissure to close in early human development. Despite significant progress in identifying genes whose regulation is important for executing this closure, mutations are detected in a minority of cases using known gene panels, implying additional genetic complexity. We have previously shown knock down of znf503 (the ortholog of mouse Zfp503) in zebrafish causes coloboma. Here we characterize Zfp503 knock out (KO) mice and evaluate transcriptomic profiling of mutant vs. wild-type (WT) retinal pigment epithelium (RPE)/Choroid.MethodsZfp503 KO mice were generated by gene targeting using homologous recombination. Embryos were characterized grossly and histologically. Patterns and level of developmentally relevant proteins/genes were examined with immunostaining/in situ hybridization. The transcriptomic profile of E11.5 KO RPE/choroid was compared to that of WT.ResultsZfp503 is dynamically expressed in developing mouse eyes and that loss of its expression results in uveal coloboma. KO embryos exhibit altered mRNA levels and expression patterns of several key transcription factors involved in eye development, including Otx2, Mitf, Pax6, Pax2, Vax1 and Vax2, resulting in reduced melanin pigmentation in the presumptive RPE and its differentiation into neural-retina-like lineages. Comparison of RNA-Seq data from wild type and KO E11.5 embryos demonstrated reduced expression of melanin-related genes and significant overlap with genes known to be dynamically regulated at the optic fissure.ConclusionsThese results demonstrate a critical role of Zfp503 in RPE differentiation and in optic fissure closure.
Greenfield FDI attractiveness index: a machine learning approach
Authors: Alon Ilan , Bretas Vanessa P.G. , Sclip Alex , Paltrinieri Andrea 
Published: March 2022

Purpose
This study aims to propose a comprehensive greenfield foreign direct investment (FDI) attractiveness index using exploratory factor analysis and automated machine learning (AML). We offer offer a robust empirical measurement of location-choice factors identified in the FDI literature through a novel method and provide a tool for assessing the countries' investment potential.

Design/methodology/approach
Based on five conceptual key sub-domains of FDI, We collected quantitative indicators in several databases with annual data ranging from 2006 to 2019. This study first run a factor analysis to identify the most important features. It then uses AML to assess the relative importance of each resultant factor and generate a calibrated index. AML computational algorithms minimize predictive errors, explore patterns in the data and make predictions in an empirically robust way.

Findings
Openness conditions and economic growth are the most relevant factors to attract FDI identified in the study. Luxembourg, Hong Kong, Singapore, Malta and Ireland are the top five countries with the highest overall greenfield attractiveness index. This study also presents specific indices for the three sectors: energy, financial services, information and communication technology (ICT) and electronics.

Originality/value
Existent indexes present deficiencies in conceptualization and measurement, lacking theoretical foundation, arbitrary selection of factors and use of limited linear models. This study’s index is developed in a robust three-stage process. The use of AML configures an advantage compared to traditional linear and additive models, as it selects the best model considering the predictive capacity of many models simultaneously.