bluuebunny/crossref_metadata_2025 huggingface dataset:
A Role for Artificial Intelligence in the Classification of Craniofacial Anomalies
Authors: Geisler Emily L. , Agarwal Saloni , Hallac Rami R. , Daescu Ovidiu , Kane Alex A.
Published: January 2021

Development of an objective algorithm to diagnose and assess craniofacial conditions has the potential to facilitate early diagnosis, especially for care providers with limited craniofacial expertise. Deep learning, a branch of artificial intelligence, can automatically analyze and categorize disease without human assistance. Convolutional neural networks (CNN) have excelled in utilizing medical images to automatically classify disease. In this study, the authors developed CNN models to detect and classify non-syndromic craniosynostosis (CS) using 2D images. The authors created an annotated data set of labeled CS (normal, metopic, sagittal, and unicoronal) conditions using standard clinical photography from the image repository at our center. The authors extended this dataset set by adding photographic images of children with craniofacial conditions from the internet. A total of 1076 images were used in this study. The authors developed a CNN model using a pre-trained ResNet-50 model to classify the data as metopic, sagittal, and unicoronal. The testing accuracy for the CS ResNet50 model achieved an overall testing accuracy of 90.6%. The sensitivity and precision were: 100% and 100% for metopic, 93.3% and 100% for sagittal, and 66.7% and 100% for unicoronal, respectively. The CNN model performed with promising accuracy. These results support the idea that deep learning has a role in diagnosis of craniofacial conditions. Using standard 2D clinical photography, such systems can provide automated screening and detection of these conditions. In the future, ML may be applied to prediction and assessment of surgical outcomes, or as an open-source remote diagnostic resource.
Comparison of Donor Site Morbidity Between Anterolateral Thigh and Radial Forearm Free Flaps for Head and Neck Reconstruction: A Systematic Review and Meta-Analysis
Authors: Niu Zehao , Chen Youbai , Li Yan , Tao Ran , Lei Yonghong , Guo Lingli , Zhang Fugui , Zhang Haizhong , Zhang Qixu , August Meredith , Han Yan
Published: January 2021

This meta-analysis aimed to provide an up-to-date comparison of donor site morbidity (DSM) between patients who underwent head and neck reconstruction with Anterolateral thigh (ALT) and radial forearm free (RFF) flaps. We searched the PubMed, Web of Science, EMBASE, and Cochrane Library databases to identify studies that compared DSM between ALT and RFF patients. Study quality was assessed using the Newcastle-Ottawa Scale. The pooled odds ratio (OR) of each DSM between ALT and RFF patients was estimated using a random- or fixed-effect model depending on the degree of interstudy heterogeneity. Sensitivity and subgroup analyses were performed if substantial heterogeneity was detected. Eighteen cohort studies with 1,018 patients (535 ALT and 483 RFF patients) were included. Compared with RFF, ALT were associated with lower risks of wound dehiscence (OR = 0.2, 95%CI: 0.10-0.42, P < 0.01), strength impairment (OR = 0.18, 95%CI: 0.07-0.47, P < 0.01), and movement impairment (OR = 0.19, 95%CI:0.07-0.49, P < 0.01). A subgroup analysis showed that ALT were associated with a lower risk of donor site numbness among patients undergoing tongue reconstruction (OR = 0.05, 95%CI: 0.01-0.25, P < 0.01), but not among all patients undergoing head and neck reconstruction. The pooled ORs of other DSMs demonstrated no significant difference between ALT and RFF patients. ALT are superior to RFF for head and neck reconstruction in terms of donor site wound dehiscence, strength impairment, movement impairment, and for tongue reconstruction specifically in terms of donor site numbness. No significant differences in the incidence of donor site hematoma/seroma, infection, or dissatisfaction with donor site appearance were identified between ALT and RFF patients.
Cadaveric Costal Cartilage Grafts in Rhinoplasty and Septorhinoplasty: A Systematic Review and Meta-Analysis of Patient-Reported Functional Outcomes and Complications
Authors: Pfaff Miles J. , Bertrand Anthony A. , Lipman Kelsey J. , Malapati Sri Harshini , Kim Daniel H. , Rezzadeh Kameron S. , Roostaeian Jason
Published: January 2021

Irradiated cadaveric costal cartilage (CC) has been utilized as an alternative to autologous cartilage (AC) in functional and aesthetic nasal surgery. The impact of graft choice between AC and CC on functional outcomes in rhinoplasty has yet to be studied. A systematic review was performed in PubMed, Embase, and Cochrane databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify comparative studies evaluating the efficacy and safety of CC in nasal surgery. Functional and aesthetic outcomes and complications were reviewed and compared between AC and CC. Meta-analytic comparisons were performed when appropriate using data from comparative studies using a random-effects model. Four studies met inclusion criteria. The indication for surgery was functional in the majority of cases, and 34.6% of cases were revision rhino- or septorhinoplasties. Disparate data across studies prevented meta-analysis on functional outcomes; however, qualitative review of function outcomes demonstrated comparable outcomes between the CC and AC groups. No differences in graft infection, warping, and resorption rates were detected. Analysis of all graft-related complications was higher in the CC group (P = 0.02); however, when AC donor site-related complications were included, no significance between the two groups was observed. In conclusion, limited, high quality data was available for analysis. Of the available studies, this systematic review suggest that the use of AC or CC may lead to comparable results in terms of functional outcomes. More long-term studies directly comparing AC and CC functional outcomes would be welcomed.
Effect of Autogenous Dentin Graft on New Bone Formation
Authors: Yüceer-Çetiner Ezgi , Özkan Nilüfer , Önger Mehmet Emin
Published: January 2021

The aim of this study is to analyze the effects of autogenous dentin graft and mixture of autogenous dentin graft and platelet-rich fibrin (PRF) applied to the tooth extraction sockets on bone healing process. A total of 57 extraction sockets in 9 patients who were planned to be treated with dental implant after tooth extraction were evaluated in this study. Extraction sockets were divided randomly into 3 groups for each patient. In the first group, sockets were filled with autogenous dentin graft (Group D). In the second group, sockets were filled with the mixture of PRF and autogenous dentin graft (Group DP). In the third group, sockets were left empty as the control group (Group C). After 3 months, histological and immunohistochemical evaluations were performed on the samples taken during the implant surgery. Additionally, samples obtained from each group were examined by scanning electron microscopy. According to the histopathological findings, when the groups were compared in terms of new bone formation there was a significant difference between Group DP, both Group C, and Group D (P = 0.00), (P = 0.001). These findings supported by immunohistochemical results that showing increased bone morphogenetic protein-2 and Runt-related transcription factor-2 expression in Group DP. It has been concluded that undemineralized autogenous dentin graft has bone formation capacity on early period of bone healing. It can be used as bone graft material in augmentation procedures and its combined use with PRF accelerates new bone formation.
Evaluation of Alveolar Bone Quality: Correlation Between Histomorphometric Analysis and Lekholm and Zarb Classification
Authors: Oliveira Marina Reis , Gonçalves Andréa , Gabrielli Marisa Aparecida Cabrini , de Andrade Cleverton Roberto , Vieira Eduardo Hochuli , Pereira-Filho Valfrido Antonio
Published: January 2021

Objectives:

This study evaluated the bone quality of the maxilla and mandible by using the classification proposed by Lekholm and Zarb (L & Z) and histomorphometry.

Methods:

Sixty edentulous areas were evaluated. The classification by L & Z was obtained through the evaluation of periapical and panoramic radiographs associated with the surgeon's tactile perception during milling and implant installation. Before implant installation, bone biopsies of standardized sizes were performed for histological evaluation.

Results:

Type III bone quality was more frequent in the posterior (73.33%) and anterior (73.33%) maxilla, whereas type II bone quality was more frequent in the posterior (53.33%) and anterior (60.00%) mandible. Through histometry, statistical difference was observed for the amount of bone tissue of the posterior region of the maxilla in relation to the anterior and posterior regions of the mandible (P≤ 0.043). However, there was no difference in osteocyte counts between alveolar regions (P = 0.2946). In the female gender, the age showed a low positive correlation with the L & Z classification (rho = 0.398;P = 0.006) and in the male gender, a moderate negative correlation was observed (rho = –0.650,P = 0.016).

Conclusions:

Both methods detected differences in the bone quality of the alveolar regions of the maxilla/mandible and that the classification by L & Z is a reliable method, since it was consistent with histomorphometry, considered the “gold standard” method for the evaluation of bone quality and greater bone density was observed in older men.
One-Half Wedge Osteotomy Genioplasty for Correction of Chin Deviation Based on Three-Dimensional Computed Tomography Measurements and Simulation
Authors: Jiang Yerong , Yang Bin , Yang Fan , Li Binghang , Ma Hengyuan , Huang Qinghua , Sun Tiecheng , Lei Bowen , Shuang Kun
Published: January 2021

Conventional operations correcting chin deviations mainly rely on the observation and experience of the surgeons during the operation. We have created a new surgical method, one-half wedge osteotomy genioplasty (1/2WOG), that combines three-dimensional computed tomography measurements and simulation. This study evaluated the clinical effect of chin deviation correction with the 1/2WOG method. A total of 38 patients (15 men and 23 women) who underwent 1/2WOG between October 2019 and October 2014 were evaluated. The chin deviation angle and distance, and partial chin deformity were measured preoperatively using three-dimensional computed tomography data. Precise calculations and osteotomy lines were achieved by preoperative simulation. All patients underwent the same surgery by the same surgical team. The clinical effect of 1/2WOG was evaluated according to the preoperative and postoperative data and patient satisfaction. All 38 patients achieved satisfactory aesthetic results without major complications such as chin nerve injury or bone nonunion. Eight patients occured numbness of the lower lip after surgery; at 6-month follow-up, the numbness was reduced in 2 patients and disappeared in 6 patients. Compared with preoperative data, the chin deviation angle, chin deviation distance, and gonion-menton difference were significantly reduced postoperatively. During the 12-month follow-up, the patient satisfaction rate reached 90%. We conclude that chin deviation can be improved by 1/2WOG. The combination of digital technology measurements and simulation can increase the accuracy of the osteotomy line design, thus reducing surgical trauma and increasing patient satisfaction, which is worthy of clinical promotion.
Whole-exome Sequencing Identifies SLC52A1 and ZNF106 Variants as Novel Genetic Risk Factors for (Early) Multiple-organ Failure in Acute Pancreatitis
Authors: van den Berg Fons F. , Issa Yama , Vreijling Jeroen P. , Lerch Markus M. , Weiss Frank Ulrich , Besselink Marc G. , Baas Frank , Boermeester Marja A. , van Santvoort Hjalmar C.
Published: January 2021

Objective:

The aim of this study was to identify genetic variants associated with early multiple organ failure (MOF) in acute pancreatitis.

Summary Background Data:

MOF is a life-threatening complication of acute pancreatitis, and risk factors are largely unknown, especially in early persistent MOF. Genetic risk factors are thought to enhance severity in complex diseases such as acute pancreatitis.

Methods:

A 2-phase study design was conducted. First, we exome sequenced 9 acute pancreatitis patients with early persistent MOF and 9 case-matched patients with mild edematous pancreatitis (phenotypic extremes) from our initial Dutch cohort of 387 patients. Secondly, 48 candidate variants that were overrepresented in MOF patients and 10 additional variants known from literature were genotyped in a replication cohort of 286 Dutch and German patients.

Results:

Exome sequencing resulted in 161,696 genetic variants, of which the 38,333 non-synonymous variants were selected for downstream analyses. Of these, 153 variants were overrepresented in patients with multiple-organ failure, as compared with patients with mild acute pancreatitis. In total, 58 candidate variants were genotyped in the joined Dutch and German replication cohort. We found the rs12440118 variant of ZNF106 to be overrepresented in patients with MOF (minor allele frequency 20.4% vs 11.6%, P

adj=
0.026). Additionally, SLC52A1 rs346821 was found to be overrepresented (minor allele frequency 48.0% vs 42.4%, P

adj

= 0.003) in early MOF. None of the variants known from literature were associated.

Conclusions: This study indicates that SLC52A1, a riboflavin plasma membrane transporter, and ZNF106, a zinc finger protein, may be involved in disease progression toward (early) MOF in acute pancreatitis.
Prospective Assessment of a Protocol Using Neuromonitoring, Early Limb Reperfusion, and Selective Temporary Aneurysm Sac Perfusion to Prevent Spinal Cord Injury During Fenestrated-branched Endovascular Aortic Repair
Authors: Tenorio Emanuel R. , Ribeiro Mauricio S. , Banga Peter V. , Mendes Bernardo C. , Kärkkäinen Jussi , DeMartino Randall R. , Hoffman Ernest M. , Oderich Gustavo S.
Published: January 2021

Objective:

The aim of this study was to analyze the outcomes of a standardized protocol using routine CSFD, neuromonitoring, LL reperfusion, and selective TASP to prevent SCI during F-BEVAR.

Background:

SCI is to be the most devastating complication for the patient, family, and surgeon, with impact on patient’s quality of life and long-term prognosis. An optimal standardized protocol may be used to improve outcomes.

Methods:

Patients enrolled in a prospective, nonrandomized single-center study between 2013 and 2018. A SCI prevention protocol was used for TAAAS or complex abdominal aneurysms with ≥5-cm supraceliac coverage including CSFD, neuromonitoring, LL reperfusion, and selective TASP. Endpoints included mortality and rates of SCI.

Results:

SCI prevention protocol was used in 170 of 232 patients (73%) treated by F-BEVAR. Ninety-one patients (55%) had changes in neuromonitoring, which improved with maneuvers in all except for 9 patients (10%) who had TASP. There was one 30-day or in-hospital mortality (0.4%). Ten patients (4%) developed SCIs including in 1% (1/79) of patients with normal neuromonitoring and 10% (9/91) of those who had decline in neuromonitoring (P = 0.02). Permanent paraplegia occurred in 2 patients (1%). Factors associated with SCI included total operating time (odds ratio 1.5, 95% confidence interval 1.1–2.2, P = 0.02) and persistent changes in neuromonitoring requiring TASP (odds ratio 15.7, 95% confidence interval 2.9–86.2, P = 0.001).

Conclusion:

This prospective nonrandomized study using a standardized strategy to prevent SCI was associated with low incidence of the SCI during F-BEVAR. Permanent paraplegia occurred in 1%.
Same-Day Discharge After Minimally Invasive Sacrocolpopexy Is Feasible, Safe, and Associated With High Patient Satisfaction
Authors: Hickman Lisa C. , Paraiso Marie Fidela R. , Goldman Howard B. , Propst Katie , Ferrando Cecile A.
Published: January 2021

Objectives

This study aimed to compare the incidence of adverse events and postoperative health care resource utilization, as well as to determine satisfaction in patients after a same-day discharge (SDD) protocol compared with routine care (discharge ≥postoperative day 1).

Methods

This is a prospective cohort study of SDD after minimally invasive sacrocolpopexy. Eligibility criteria included age younger than 80 years, American Society of Anesthesiologists grade I/II, caretaker for ≥24 hours postoperatively, and surgical start before 1 pm. Perioperative data were obtained through the medical record and direct patient inquiry. A satisfaction survey was administered at the postoperative visit. A historical control group was used to compare outcomes.

Results

Forty-seven women met the eligibility criteria. Mean age was 62 (±9) years. Most were White (95.7%), were overweight (body mass index, 27.7 ± 5.5 kg/m2), and had stage 3 prolapse (63.8%). Same-day discharge was achieved for 37 patients (78.7%). Patient characteristics of the SDD cohort were similar to the routine-care cohort, with the exception of previous hysterectomy (57.5% vs 100.0%, P < 0.001) and the American Society of Anesthesiologists score (2 [1–2] vs 2 [1–3], P = 0.002). There were significantly fewer postoperative telephone calls in the SDD cohort but no other differences in health care resource utilization. Adverse events did not differ between groups. The SDD cohort reported high satisfaction and would recommend SDD to family or friends independent of whether or not SDD was achieved (91.9% vs 80.0%, P = 0.29).

Conclusions

Nearly 80% of women undergoing minimally invasive sacrocolpopexy on an SDD protocol went home as planned. Compared with routine care, there was no increase in adverse events or postoperative health care resource utilization. Patient satisfaction in the SDD cohort was high.

Clinical Trial Registration

Same-day discharge after minimally invasive sacrocolpopexy, https://clinicaltrials.gov/ct2/show/NCT03730103?term=same+day+discharge&cntry=US&state=US%3AOH&city=Cleveland&draw=2&rank=1; NCT03730103.
Anterior Bilateral Sacrospinous Fixation With Transvaginal Mesh: Is Hysterectomy a Risk Factor for Complications?
Authors: Breton Florence , Abdirahman Syad , Fatton Brigitte , Calletwaert Geertje , de Tayrac Renaud , Allegre Lucie
Published: January 2021

Objectives

The aim of the study was to evaluate the effect of hysterectomy on the risk of complications from transvaginal pelvic organ prolapse surgery with mesh.

Methods

We conducted a retrospective cohort study between October 2010 and December 2017. Transvaginal mesh surgery was performed in patients with symptomatic anterior and/or apical prolapse (Pelvic Organ Prolapse Quantification ≥ stage 2). The primary outcome was rate of severe surgical complications based on the Clavien-Dindo classification (defined as grade ≥3), and the secondary outcome was the anatomical success at the last postoperative follow-up visit.

Results

Three hundred and ninety-six patients were included, 289 of these patients underwent anterior sacrospinous fixation with uterine preservation, 50 had a previous hysterectomy and 57 underwent a concomitant hysterectomy. The median follow-up was 12 months (interquartile range, 7 months). The rate of severe complications was 2.1%, 6.0%, and 5.3% in the uterine preservation group, previous hysterectomy group, and concomitant hysterectomy group, respectively (P = 0.2). The operative time was significantly higher in the concomitant hysterectomy group, and the mesh exposure rate was significantly higher in the previous hysterectomy group. The overall recurrence rate was 7.6%, with no differences between the study groups.

Conclusions

Concomitant and previous hysterectomy did not appear to increase the severe complication rate or anatomical failure after transvaginal mesh surgery. However, a history of hysterectomy appears to be a risk factor for vaginal mesh exposure. This must be considered in the choice between prosthetic and autologous management options for the treatment of posthysterectomy vault prolapse.
Tourniquet application by schoolchildren—a randomized crossover study of three commercially available models
Authors: El Bashtaly Alaa , Khalil Elene , Méthot Francois , Ledoux-Hutchinson Lawrence , Franc Jeffrey M. , Homier Valérie
Published: January 2021

BACKGROUND

Life-threatening hemorrhage is a major cause of preventable mortality in trauma. Studies have demonstrated the effectiveness and safety of commercial tourniquets when used by adult civilians. However, there are no data about tourniquet application by children.

This study’s goal is to determine which of three commercially available tourniquets is most effective when used by children.

METHODS

A randomized crossover study was conducted in four elementary schools in Montreal to compare three commercially available tourniquets. The study population is primary school children aged 10 to 12 years (5th–6th grade). A total of 181 students were invited to participate; 96 obtained parental approval and were recruited. Participants underwent a short 7-minute video training on the use of three commercial tourniquets and were subsequently given a 2-minute practice period. Students were evaluated on their ability to successfully apply the tourniquet and the time to complete application. After applying all three tourniquets, the students selected their favorite model. The primary outcome is the proportion of successful applications per tourniquet model. Secondary outcomes include time to successful application for each tourniquet model and tourniquet model preference.

RESULTS

The mechanical advantage tourniquet (MAT) outperformed the combat application tourniquet (CAT) and the stretch wrap and tuck tourniquet (SWATT) in terms of success rate (MAT, 67%; CAT, 44%; SWATT, 24%; p < 0.0001), time to application (MAT, 57 seconds; CAT, 80 seconds; SWATT, 90 seconds; p < 0.0001), and preference (MAT, 64%; CAT, 30%; SWATT, 6%; p < 0.0001).

CONCLUSION

In this study, the MAT performs better in terms of success rate, time to application, and preference when used by school-aged children. This study can be helpful when facilities are purchasing tourniquets for use by students.
Redefining geriatric trauma: 55 is the new 65
Authors: Fakhry Samir M. , Morse Jennifer L. , Garland Jeneva M. , Wilson Nina Y. , Shen Yan , Wyse Ransom J. , Watts Dorraine D.
Published: January 2021

INTRODUCTION

As the prevalence of geriatric trauma patients has increased, protocols are being developed to address the unique requirements of this demographic. However, categorical definitions for geriatric patients vary, potentially creating confusion concerning which patients should be cared for according to geriatric-specific standards. The aim of this study was to identify data-driven cut points for mortality based on age to support implementation of age-driven guidelines.

METHODS

Adults aged 18 to 100 years with blunt or penetrating injury were selected from 95 hospitals’ trauma registries. Change point analysis techniques were used to detect inflection points in the proportion of deaths at each age. Based on these calculated points, patients were allocated into age groups, and their characteristics and outcomes were compared. Logistic regression was used to estimate risk-adjusted in-hospital mortality controlling for sex, race, Injury Severity Score, Glasgow Coma Scale, and number of comorbidities.

RESULTS

A total of 255,099 patients were identified (female, 45.7%; mean age, 59.3 years; mean Injury Severity Score, 8.69; blunt injury, 92.6%). Statistically significant increases in mortality rate were noted at ages 55, 77, and 82 years. Compared with the referent group (age, <55 years), adjusted odds ratios (AORs) showed increases in mortality if age 55 to 76 years (AOR, 2.42), age 77 to 81 years (AOR, 4.70), or age 82 years or older (AOR, 6.43). National Trauma Data Standard–defined comorbidities significantly increased once age surpassed 55 years, as the rate more than doubled for each of the older age categories (p < 0.001). As age increased, each group was more likely to be female, have dementia, sustain a ground level fall, and be discharged to a skilled nursing facility (p < 0.001).

CONCLUSION

This large multicenter analysis established a clinically and statistically significant increase in mortality at ages 55, 77, and 82 years. This research strongly suggests that trauma patients older than 55 years be considered for inclusion in geriatric trauma protocols. The other age inflection points identified (77 and 82 years) may also warrant additional specialized care considerations.

LEVEL OF EVIDENCE

Epidemiological study, level III; Care management, level IV.
Personal protective equipment for reducing the risk of COVID-19 infection among health care workers involved in emergency trauma surgery during the pandemic: An umbrella review
Authors: Griswold Dylan P. , Gempeler Andres , Kolias Angelos , Hutchinson Peter J. , Rubiano Andres M.
Published: January 2021

BACKGROUND

Health care facilities in low- and middle-income countries are inadequately resourced to adhere to current COVID-19 prevention recommendations. Recommendations for surgical emergency trauma care measures need to be adequately informed by available evidence and adapt to particular settings. To inform future recommendations, we set to summarize the effects of different personal protective equipment (PPE) on the risk of COVID-19 infection in health personnel caring for trauma surgery patients.

METHODS

We conducted an umbrella review using Living Overview of Evidence platform for COVID-19, which performs regular automated searches in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and more than 30 other sources. Systematic reviews of experimental and observational studies assessing the efficacy of PPE were included. Indirect evidence from other health care settings was also considered. Risk of bias was assessed with the AMSTAR II tool (Assessing the Methodological Quality of Systematic Reviews, Ottawa, ON, Canada), and the Grading of Recommendations, Assessment, Development, and Evaluation approach for grading the certainty of the evidence is reported (registered in International Prospective Register of Systematic Reviews, CRD42020198267).

RESULTS

Eighteen studies that fulfilled the selection criteria were included. There is high certainty that the use of N95 respirators and surgical masks is associated with a reduced risk of COVID-19 when compared with no mask use. In moderate- to high-risk environments, N95 respirators are associated with a further reduction in risk of COVID-19 infection compared with surgical masks. Eye protection also reduces the risk of contagion in this setting. Decontamination of masks and respirators with ultraviolet germicidal irradiation, vaporous hydrogen peroxide, or dry heat is effective and does not affect PPE performance or fit.

CONCLUSION

The use of PPE drastically reduces the risk of COVID-19 compared with no mask use in health care workers. N95 and equivalent respirators provide more protection than surgical masks. Decontamination and reuse appear feasible to overcome PPE shortages and enhance the allocation of limited resources. These effects are applicable to emergency trauma care and should inform future recommendations.

LEVEL OF EVIDENCE

Review, level II.
Presence of Donor Lymph Nodes Within Vascularized Composite Allotransplantation Ameliorates VEGF-C-mediated Lymphangiogenesis and Delays the Onset of Acute Rejection
Authors: Olariu Radu , Tsai Catherine , Abd El Hafez Mai , Milusev Anastasia , Banz Yara , Lese Ioana , Leckenby Jonathan I. , Constantinescu Mihai , Rieben Robert , Vögelin Esther , Taddeo Adriano
Published: January 2021

Background.

The lymphatic system plays an active role in modulating inflammation in autoimmune diseases and organ rejection. In this work, we hypothesized that the transfer of donor lymph node (LN) might be used to promote lymphangiogenesis and influence rejection in vascularized composite allotransplantation (VCA).

Methods.

Hindlimb transplantations were performed in which (1) recipient rats received VCA containing donor LN (D:LN+), (2) recipient rats received VCA depleted of all donor LN (D:LN−), and (3) D:LN+ transplantations were followed by lymphangiogenesis inhibition using a vascular endothelial growth factor receptor-3 (VEGFR3) blocker.

Results.

Our data show that graft rejection started significantly later in D:LN+ transplanted rats as compared to the D:LN− group. Moreover, we observed a higher level of VEGF-C and a quicker and more efficient lymphangiogenesis in the D:LN+ group as compared to the D:LN− group. The presence of donor LN within the graft was associated with reduced immunoactivation in the draining LN and increased frequency of circulating and skin-resident donor T regulatory cells. Blocking of the VEGF-C pathway using a VEGFR3 blocker disrupts the lymphangiogenesis process, accelerates rejection onset, and interferes with donor T-cell migration.

Conclusions.

This study demonstrates that VCA LNs play a pivotal role in the regulation of graft rejection and underlines the potential of specifically targeting the LN component of a VCA to control graft rejection.
Evaluation Within 30 Days of Referral for Liver Transplantation is Associated with Reduced Mortality: A Multicenter Analysis of Patients Referred Within the VA Health System
Authors: John Binu V. , Schwartz Kaley , Scheinberg Andrew R. , Dahman Bassam , Spector Seth , Deng Yangyang , Goldberg David , Martin Paul , Taddei Tamar H. , Kaplan David E.
Published: January 2021

Background.

Successful liver transplantation offers the possibility of improved survival among patients with decompensated cirrhosis. However, there is wide variability in access to care and promptness of the transplant evaluation process in the United States.

Methods.

We performed a multicenter retrospective study of 1118 patients who underwent evaluation for liver transplantation at the 6 Veterans Affairs’ transplant centers from 2013 to 2018. Of these, 832 patients were evaluated within 30 d and 286 > 30 d after referral. We studied the differential effects of the time from referral to evaluation on pretransplant and posttransplant mortality and transplant list dropout and explored predictors of early transplant evaluation.

Results.

Patients in the early evaluation group had a shorter adjusted time from referral to listing by 29.5 d (95% confidence interval [CI] −50.4, −8.5, P < 0.006), and referral to transplantation by 115.1 d (95% CI −179.5, −50.7, P < 0.0001). On a multivariable Cox hazard model, evaluation within 30 d of referral was associated with a significantly lower pretransplant mortality (adjusted hazard ratio [aHR] 0.70, 95% CI 0.54-0.91, P < 0.01), but not associated with transplant list dropout (aHR 0.95, 95% CI 0.65-1.39, P = 0.79) or posttransplant death (aHR 1.88, 95% CI 0.72-4.9, P = 0.20). An early evaluation within 30 d was positively associated with a higher MELD at referral (aHR 1.03, 95% CI 1.01-1.06, P = 0.006) and negatively associated with distance from the transplant center (aHR 0.99, 95% CI 0.99-0.99, P = 0.045).

Conclusions.

Evaluation of patients referred for liver transplantation within 30 d is associated with a reduction in pretransplant mortality.
Canadian Society of Transplantation White Paper: Ethical and Legal Considerations for Alcohol and Cannabis Use in Solid Organ Listing and Allocation
Authors: Greenberg Rebecca , Goldberg Aviva , Anthony Samantha , Buchman Daniel Z. , Delaney Sean , Gruben Vanessa , Holdsworth Sandra , Le Foll Bernard , Leung Marianna , Lien Dale , Lynch Marie-Josee , Selzner Nazia , Chandler Jennifer A. , Fortin Marie-Chantal
Published: January 2021

Alcohol and cannabis use as a contraindication to organ transplantation is a controversial issue. Until recently, patients in Canada with alcohol-associated liver disease were required to demonstrate abstinence for 6 mo to receive a liver transplant. There is no equivalent rule that is applied consistently for cannabis use. There is some evidence that alcohol and cannabis use disorder pretransplant could be associated with worse outcomes posttransplantation. However, early liver transplantation for patients with alcohol-associated liver disease in France and in the United States has led to challenges of the 6-mo abstinence rule in Canada in the media. It has also resulted in several legal challenges arguing that the rule violates human rights laws regarding discrimination in the provision of medical services and that the rule is also unconstitutional (this challenge is still before the court). Recent legalization of cannabis use for adults in Canada has led to questions about the appropriateness of limiting transplant access based on cannabis use. The ethics committee of the Canadian Society of Transplantation was asked to provide an ethical analysis of cannabis and alcohol abstinence policies. Our conclusions were as follows: neither cannabis use nor the 6-mo abstinence rule for alcohol use should be an absolute contraindication to transplantation, and transplant could be offered to selected patients, further research should be conducted to ensure evidence-based policies; and the transplant community has a duty not to perpetuate stigma associated with alcohol and cannabis use disorders.
Quantitative Electroencephalography After Pediatric Anterior Circulation Stroke
Authors: Appavu Brian L. , Temkit M'hamed H. , Foldes Stephen T. , Burrows Brian T. , Jacobson Austin M. , Mangum Tara K. , Boerwinkle Varina L. , Marku Iris , Abruzzo Todd A. , Adelson Phillip D.
Published: January 2021

Objective:

Regional differences were investigated in quantitative EEG (QEEG) characteristics and associations of QEEG to hemodynamics after pediatric acute stroke.

Methods:

Quantitative EEG was analyzed, including power in delta, theta, alpha, and beta bands, alpha–delta power ratio, total power, and spectral edge frequency from 11 children with unilateral, anterior circulation strokes during the first 24 hours of continuous EEG recording. Differences between injured and uninjured hemispheres were assessed using multivariate dynamic structural equations modeling. Dynamic structural equations modeling was applied to six children with hemorrhagic stroke undergoing arterial blood pressure, heart rate, and cerebral oximetry monitoring to investigate associations between hemodynamics with QEEG adjacent to anterior circulation regions.

Results:

All patients with acute ischemic stroke (n = 5) had lower alpha and beta power and spectral edge frequency on injured compared with uninjured regions. This was not consistent after hemorrhagic stroke (n = 6). All hemorrhagic stroke patients demonstrated negative association of total power with arterial blood pressure within injured regions. No consistency was observed for direction or strength of association in other QEEG measures to arterial blood pressure nor were such consistent relationships observed for any QEEG measure studied in relation to heart rate or cerebral oximetry.

Conclusions:

After pediatric anterior circulation acute ischemic stroke, reduced spectral edge frequency and alpha and beta power can be observed on injured as compared with noninjured regions. After pediatric anterior circulation hemorrhagic stroke, total power can be negatively associated with arterial blood pressure within injured regions. Larger studies are needed to understand conditions in which QEEG patterns manifest and relate to hemodynamics and brain penumbra.
Magnetic transfection with superparamagnetic chitosan-loaded IGFBP5nanoparticles and theirin vitrobiosafety
Authors: Tang Yue , Wu Jun , Zhang Yuan , Ju Lingpeng , Qu Xiangyang , Jiang Dianming
Published: January 2021

We prepared the superparamagnetic chitosan nanoparticles (SPCIONPs) to study the application of them as gene vectors using a magnetic transfection system for the targeted treatment of lung metastasis of osteosarcoma. The SPCIONPs were characterized by transmission electron microscopy, Fourier transform infrared spectrometry, superconducting quantum interference device and atomic force microscopy. Their biosafety was determined by cell counting kit-8 (CCK8) and live–dead staining assays. The transfectionin vitrowas detected by laser confocal microscopy. SPCIONPs, which can bind closely to plasmids and protect them from DNA enzyme degradation, were prepared with an average particle size of approximately 22 nm and zeta potential of 11.3 mV. The results of the CCK8 and live–dead staining assays showed that superparamagnetic chitosan nanoparticles loaded with insulin-like growth factor-binding protein 5 (SPCIONPs/pIGFBP5) induced no significant cytotoxicity compared to the control group. The result of transfectionin vitrosuggested that pIGFBP5emitted a greater amount of red fluorescence in the SPCIONPs/pIGFBP5group than that in the chitosan-loaded IGFBP5(CS/pIGFBP5) group. In conclusion, the prepared SPCIONPs had good biosafety and could be effectively used to transfer pIGFBP5into 143B cells, and they thus have good application prospects for the treatment of lung metastasis of osteosarcoma.
The development and psychometric properties of a self-report Catastrophizing Questionnaire
Authors: Pike Alexandra C. , Serfaty Jade R. , Robinson Oliver J.
Published: January 2021

Catastrophizing is a cognitive process that can be defined as predicting the worst possible outcome. It has been shown to be related to psychiatric diagnoses such as depression and anxiety, yet there are no self-report questionnaires specifically measuring it outside the context of pain research. Here, we therefore develop a novel, comprehensive self-report measure of general catastrophizing. We performed five online studies (totaln= 734), in which we created and refined a Catastrophizing Questionnaire, and used a factor analytic approach to understand its underlying structure. We also assessed convergent and discriminant validity, and analysed test–retest reliability. Furthermore, we tested the ability of Catastrophizing Questionnaire scores to predict relevant clinical variables over and above other questionnaires. Finally, we also developed a four-item short version of this questionnaire. We found that our questionnaire is best fit by a single underlying factor, and shows convergent and discriminant validity. Exploratory factor analyses indicated that catastrophizing is independent from other related constructs, including anxiety and worry. Moreover, we demonstrate incremental validity for this questionnaire in predicting diagnostic and medication status. Finally, we demonstrate that our Catastrophizing Questionnaire has good test–retest reliability (intraclass correlation coefficient = 0.77,p< 0.001). Critically, we can now, for the first time, obtain detailed self-report data on catastrophizing.
Bi-enzymes treatments attenuate cognitive impairment associated with oxidative damage of heavy metals
Authors: Chen Chao , Zhang Xiaoxin , Huang Hao , Bao Hongyi , Li Xiaodong , Cheng Ye , Zhang Jing , Ding Yin , Yang Yanguang , Gu Haiying , Xia Donglin
Published: January 2021

Oxidative stress has been implicated in the pathogenesis of cognitive impairment. Lead (Pb) is a common environmental toxicant and plays a vital role in oxidative stress activation. In this study, a superoxide dismutase (SOD) and catalase (CAT) containing poly (lactic-co-glycolic acid) (PLGA) meso-particles (PLGA@SOD-CAT) were prepared to attenuate cognitive impairment via inhibiting oxidative stress in rats. It was prepared using a double emulsion (water/oil/water phase) technique to minimize the hazardous effects of Pb burden on cognitive impairment. The meso-particles antagonized the Pb-induced cognitive impairments. Behaviour, serum biochemical parameters and biomarkers of oxidative stress in rats were evaluated after they were subjected to intravenous injection with lead nitrate and PLGA@SOD-CAT. Moreover, the potential protective mechanism of PLGA@SOD-CAT was determined. Notably, PLGA@SOD-CAT appreciably agented memory impairment caused by lead nitrate and it could significantly inhibit Pb-induced oxidative stress in the blood. Furthermore, a remarkable reversion effect of cognitive impairments, including escape latency, crossing platform times and time per cent during the platform quadrant, after PLGA@SOD-CAT administration were noted. Therefore, these results suggested that the bi-enzymes platform was a superior product in eliminating Pb-induced cognitive impairments through reducing expression of Pb-associated oxidative stress, and it could potentially be applied in detoxifying heavy metals in blood circulation.
Evaluation of Ultrafast Wave-CAIPI 3D FLAIR in the Visualization and Volumetric Estimation of Cerebral White Matter Lesions
Authors: Ngamsombat Chanon , Gonçalves Filho Augusto Lio M. , Figueiro Longo M. Gabriela , Cauley Stephen F. , Setsompop Kawin , Kirsch John E. , Tian Qiyuan , Fan Qiuyun , Polak Daniel , Liu Wei , Lo Wei-Ching , González R. Gilberto , Schaefer Pamela W. , Rapalino Otto , Conklin John , Huang Susie Y.
Published: January 2021

BACKGROUND AND PURPOSE

To evaluate an ultrafast 3D-FLAIR sequence using Wave-CAIPI encoding (Wave-FLAIR) compared to standard 3D-FLAIR in the visualization and volumetric estimation of cerebral white matter lesions in a clinical setting.

MATERIALS AND METHODS

42 consecutive patients underwent 3T brain MRI including standard 3D-FLAIR (acceleration factor R=2, scan time TA=7:15 minutes) and resolution-matched ultrafast Wave-FLAIR sequences (R=6, TA=2:45 minutes for the 20-ch coil; R=9, TA=1:50 minutes for the 32-ch coil) as part of clinical evaluation for demyelinating disease. Automated segmentation of cerebral white matter lesions was performed using the Lesion Segmentation Tool in SPM. Student’s t-test, intra-class correlation coefficient (ICC), relative lesion volume difference (LVD) and Dice similarity coefficients (DSC) were used to compare volumetric measurements between sequences. Two blinded neuroradiologists evaluated the visualization of white matter lesions, artifact and overall diagnostic quality using a predefined 5-point scale.

RESULTS

Standard and Wave-FLAIR sequences showed excellent agreement of lesion volumes with an ICC of 0.99 and DSC of 0.97±0.05 (range 0.84 to 0.99). Wave-FLAIR was non-inferior to standard-FLAIR for visualization of lesions and motion. The diagnostic quality for Wave-FLAIR was slightly greater than standard-FLAIR for infratentorial lesions (p<0.001), and there was less pulsation artifact on Wave-FLAIR compared to standard FLAIR (p<0.001).

CONCLUSIONS

Ultrafast Wave-FLAIR provides superior visualization of infratentorial lesions while preserving overall diagnostic quality and yields comparable white matter lesion volumes to those estimated using standard-FLAIR. The availability of ultrafast Wave-FLAIR may facilitate the greater use of 3D-FLAIR sequences in the evaluation of patients with suspected demyelinating disease.
Local genetic context shapes the function of a gene regulatory network
Authors: Nagy-Staroń Anna , Tomasek Kathrin , Carter Caroline Caruso , Sonnleitner Elisabeth , Kavčič Bor , Paixão Tiago , Guet Călin C.
Published: January 2021

Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions, such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks remains a major challenge. Here, we use a well-defined synthetic gene regulatory network to study how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one gene regulatory network with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Our results demonstrate that changes in local genetic context can place a single transcriptional unit within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual transcriptional units, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of gene regulatory networks.
IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity toToxoplasma gondii
Authors: Clark Joseph T. , Christian David A. , Gullicksrud Jodi A. , Perry Joseph A. , Park Jeongho , Jacquet Maxime , Tarrant James C. , Radaelli Enrico , Silver Jonathan , Hunter Christopher A.
Published: January 2021

IL-33 is an alarmin required for resistance to the parasiteToxoplasma gondii, but its role in innate resistance to this infection is unclear.T. gondiiinfection promotes increased stromal cell expression of IL-33 and levels of parasite replication correlate with IL-33 release. In response to infection, a subset of innate lymphoid cells (ILC) emerges composed of IL-33R+NK cells and ILC1s. In Rag-/-mice, where NK cells and ILC1 provide an innate mechanism of resistance toT. gondii, the loss of IL-33R reduced ILC responses and increased parasite replication. Furthermore, administration of IL-33 to Rag-/-mice resulted in a marked decrease in parasite burden, increased production of IFN-γ and the recruitment and expansion of inflammatory monocytes associated with parasite control. These protective effects of exogenous IL-33 were dependent on endogenous IL-12p40 and the ability of IL-33 to enhance ILC production of IFN-γ. These results highlight that IL-33 synergizes with IL-12 to promote ILC-mediated resistance toT. gondii.
Rapid mechanical stimulation of inner-ear hair cells by photonic pressure
Authors: Abeytunge Sanjeewa , Gianoli Francesco , Hudspeth A.J. , Kozlov Andrei S.
Published: January 2021

Hair cells, the receptors of the inner ear, detect sounds by transducing mechanical vibrations into electrical signals. From the top surface of each hair cell protrudes a mechanical antenna, the hair bundle, which the cell uses to detect and amplify auditory stimuli, thus sharpening frequency selectivity and providing a broad dynamic range. Current methods for mechanically stimulating hair bundles are too slow to encompass the frequency range of mammalian hearing and are plagued by inconsistencies. To overcome these challenges, we have developed a method to move individual hair bundles with photonic force. This technique uses an optical fiber whose tip is tapered to a diameter of a few micrometers and endowed with a ball lens to minimize divergence of the light beam. Here we describe the fabrication, characterization, and application of this optical system and demonstrate the rapid application of photonic force to vestibular and cochlear hair cells.
Computationally scalable regression modeling for ultrahigh-dimensional omics data with ParProx
Authors: Ko Seyoon , Li Ginny X. , Choi Hyungwon , Won Joong-Ho
Published: January 2021

Statistical analysis of ultrahigh-dimensional omics scale data has long depended on univariate hypothesis testing. With growing data features and samples, the obvious next step is to establish multivariable association analysis as a routine method for understanding genotype-phenotype associations. Here we present ParProx, a state-of-the-art implementation to optimize overlapping group lasso regression models for time-to-event and classification analysis, guided by biological priors through coordinated variable selection. ParProx not only enables model fitting for ultrahigh-dimensional data within the architecture for parallel or distributed computing, but also allows users to obtain interpretable regression models consistent with known biological relationships among the independent variables, a feature long neglected in statistical modeling of omics data. We demonstrate ParProx using three different omics data sets of moderate to large numbers of variables, where we use genomic regions and pathways to arrive at sparse regression models comprised of biologically related independent variables. ParProx is naturally applicable to a wide range of studies using ultrahigh-dimensional omics data, ranging from genome-wide association analysis to single cell sequencing studies where multivariable modeling is computationally intractable.