bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-dimensional gait characteristics of patients after unilateral total knee arthroplasty
Authors: Wang Zong-Han , Wang Jin-Cheng , Zheng Shuang , Xue Pan , Han Fu-Jun
Published: August 2021

The purpose of this study is to evaluate the gait characteristics of bilateral limbs after unilateral total knee arthroplasty (TKA) using three-dimensional (3D) dynamic capture technology.

Forty-two patients who underwent TKA were selected from the Orthopedic Medical Center of The Second Hospital of Jilin University from November 2018 to May 2019. We used a 3D dynamic capture system to measure the gait characteristics of patients at 3 months after TKA. The data, including relative position and direction of different body parts, the force between feet and ground, spatial and temporal relationship of the lower limb muscles, were measured. Besides, the surface electromyogram signal and the force plate analog signal were also collected. The walking ability, knee 3D kinematic, and kinetic characteristics were analyzed by the Cortex software.

Spatial and temporal parameters, including stride frequency, double support phase, single support phase, step length, step time, step width, stride length, gait cycle, velocity, were no significant difference in bilateral lower extremities (P > .05). The reaction force of hip, knee, and ankle joint in the operation side were less than that of the healthy side, but the difference was not statistically significant (P > .05). However, when compared with the healthy side, the hip joint in operation side had a larger maximum extension angle (P < .001), the knee joint in operation side had a larger maximum valgus angle and valgus activity (P < .05), and had a smaller tibial maximum internal rotation angle (P < .05). Besides, the surface electromyogram signals of tibialis anterior muscles were reduced (P < .05).

3D gait analysis, as an objective and quantitative evaluation method, is a safe, effective, and reliable method for evaluating postoperative knee function. The data of gait analysis prove that TKA is a vital treatment to improve the function of patients with knee arthritis. Besides, gait analysis also showed that there were various kinematic and biomechanical abnormalities in the knee after TKA, which may be the reason why the surgical knee could not immediately return to normal level.
Protective efficient comparisons among all kinds of respirators and masks for health-care workers against respiratory viruses
Authors: Li Jiawen , Qiu Yu , Zhang Yulin , Gong Xue , He Yunru , Yue Peng , Zheng Xiaolan , Liu Lei , Liao Hongyu , Zhou Kaiyu , Hua Yimin , Li Yifei
Published: August 2021

Background:

There is no definite conclusion about comparison of better effectiveness between N95 respirators and medical masks in preventing health-care workers (HCWs) from respiratory infectious diseases, so that conflicting results and recommendations regarding the protective effects may cause difficulties for selection and compliance of respiratory personal protective equipment use for HCWs, especially facing with pandemics of corona virus disease 2019.

Methods:

We systematically searched MEDLINE, Embase, PubMed, China National Knowledge Infrastructure, Wanfang, medRxiv, and Google Scholar from initiation to November 10, 2020 for randomized controlled trials, case-control studies, cohort studies, and cross-sectional studies that reported protective effects of masks or respirators for HCWs against respiratory infectious diseases. We gathered data and pooled differences in protective effects according to different types of masks, pathogens, occupations, concurrent measures, and clinical settings. The study protocol is registered with PROSPERO (registration number: 42020173279).

Results:

We identified 4165 articles, reviewed the full text of 66 articles selected by abstracts. Six randomized clinical trials and 26 observational studies were included finally. By 2 separate conventional meta-analyses of randomized clinical trials of common respiratory viruses and observational studies of pandemic H1N1, pooled effects show no significant difference between N95 respirators and medical masks against common respiratory viruses for laboratory-confirmed respiratory virus infection (risk ratio 0.99, 95% confidence interval [CI] 0.86–1.13, I2 = 0.0%), clinical respiratory illness (risk ratio 0.89, 95% CI 0.45–1.09, I2 = 83.7%, P = .002), influenza-like illness (risk ratio 0.75, 95% CI 0.54–1.05, I2 = 0.0%), and pandemic H1N1 for laboratory-confirmed respiratory virus infection (odds ratio 0.92, 95% CI 0.49–1.70, I2 = 0.0%, P = .967). But by network meta-analysis, N95 respirators has a significantly stronger protection for HCWs from betacoronaviruses of severe acute respiratory syndrome, middle east respiratory syndrome, and corona virus disease 2019 (odds ratio 0.43, 95% CI 0.20–0.94).

Conclusions:

Our results provide moderate and very-low quality evidence of no significant difference between N95 respirators and medical masks for common respiratory viruses and pandemic H1N1, respectively. And we found low quality evidence that N95 respirators had a stronger protective effectiveness for HCWs against betacoronaviruses causative diseases compared to medical masks. The evidence of comparison between N95 respirators and medical masks for corona virus disease 2019 is open to question and needs further study.
Impact of the implementation of a standard for preanalytical handling of samples for microbiological diagnostics on the quality of results at a neurocritical care unit
Authors: Kieninger Martin , Mandlinger Andreas , Doblinger Nina , Kieninger Bärbel , Bele Sylvia , Salzberger Bernd , Schneider-Brachert Wulf , Graf Bernhard , Zeman Florian , Holzmann Thomas
Published: August 2021

Antibiotic stewardship (ABS) programs intend to improve outcomes of nosocomial infections and to counteract the emergence of further antimicrobial resistances. At the anesthesiologic-neurosurgical intensive care unit (ICU) of the University Medical Center Regensburg (Germany) we implemented a standard operating procedure (SOP) with clear instructions for the preanalytical handling and storage of microbiological samples. We intended to find out whether the instructions given in the SOP led to a higher rate of ideal material being sent to the laboratory and to overall better quality of the received results.

We retraced retrospectively all samples taken in cases of suspected pneumonia, urinary tract infection, bloodstream infection, catheter infection associated with a central venous or arterial catheter and ventriculitis due to external ventricular drainage as well as all smears taken for the screening for multi-resistant bacteria within a time period of 1 year before to 1 year after the implementation of the SOP.

In the case of suspected pneumonia and urinary tract infection, large amounts of ideal material were sent to the microbiological laboratory. A remarkable improvement after the implementation of the SOP, however, could only be observed regarding the number of urine samples taken from older urinary catheters, which was significantly lower in the “SOP group”. Samples for microbiological diagnostics were taken much more often in the daytime, although storage of the probes did not lead to worse results.

Concrete instructions enable adequate preanalytical handling of microbiological probes. However, we could not recognize substantial improvements probably due to a preexisting high process quality on the ICU. Microbiological diagnostics during the night shift has to be improved.
Neuromyelitis Optica Spectrum Disorder Manifested by Persistent Hiccups and Severe Esophagitis in an Adolescent Patient
Authors: Singh Priya , Garcia Reinaldo , Y. Phadke Madhura
Published: August 2021

Patients with persistent hiccups are often referred to gastrointestinal services. Hiccups lasting greater than 48 hours are classified as persistent, while those lasting longer than 2 months are termed intractable. The etiology of hiccups is broad and can include many organ systems. Here, we present the case of an 18-year-old male patient who presented to the emergency department with an 8-day history of nausea, emesis, and intermittent hiccups. The patient was admitted to the gastroenterology service and underwent workup including esophagogastroduodenoscopy and imaging. Esophagogastroduodenoscopy revealed severe distal esophagitis. He was started on high-dose proton pump inhibitor and sucralfate. During the course of hospital admission, the patient’s intermittent hiccups worsened to become constant. Several medical therapies led to little improvement. We initially felt that the esophagitis was the etiology of the patient’s symptoms, however, due to ongoing symptoms unresponsive to typical therapy, we obtained a neurological consult. Brain MRI revealed a dorsal medullary lesion. Subsequent work up confirmed the diagnosis of neuromyelitis optica spectrum disorder. Neuromyelitis optica spectrum disorder is a rare, serious, sometimes fatal autoimmune condition of the central nervous system. Early diagnosis and treatment are important predictors of future relapses. Our patient was started on high-dose intravenous steroids with rapid improvement in symptoms. He was discharged home on steroids, proton pump inhibitor and close neurology and gastroenterology follow up. This case outlines the importance of consideration of neurological causes of hiccups or other centrally mediated conditions with gastrointestinal manifestations, even when a concomitant gastrointestinal condition is present.
Evaluation of Data Sources for Carbon Monoxide Poisoning Surveillance in New York City
Authors: Goldberg Rebecca , McKelvey Wendy , Lane Kathryn , Parton Hilary , Su Mark K.
Published: August 2021

Context:

Carbon monoxide (CO) exposure can be life-threatening. Suspected and confirmed cases of CO poisoning warranting health care in New York City (NYC) are reportable to the NYC Poison Control Center (PCC).

Objectives:

We evaluated 4 hospital-based sources of CO surveillance data to identify ways to improve data capture and reporting.

Design:

Suspected and confirmed CO poisoning records from October 2015 through December 2016 were collected from the NYC emergency department (ED) syndromic surveillance system, New York State Statewide Planning and Research Cooperative System (SPARCS) ED billing data, NYC PCC calls made from hospitals, and the Electronic Clinical Laboratory Reporting System (ECLRS). Syndromic and SPARCS records were person- and visit-matched. SPARCS and ECLRS records were also matched to PCC records on combinations of name, demographic characteristics, and visit information.

Setting:

Hospitals in NYC.

Participants:

Individuals who visited NYC hospitals for CO-related health effects.

Main Outcome Measures:

We assessed the validity of syndromic data, with SPARCS records as the gold standard. We matched SPARCS and ECLRS records to PCC records to analyze reporting rates by case characteristics.

Results:

The sensitivity of syndromic surveillance was 60% (225 true-positives detected among 372 visit-matched SPARCS cases), and positive predictive value was 46%. Syndromic records often missed CO flags because of a nonspecific or absent International Classification of Diseases code in the diagnosis field. Only 15% of 428 SPARCS records (total includes 56 records not visit-matched to syndromic) and 16% of 199 ECLRS records were reported to PCC, with male sex and younger age associated with higher reporting.

Conclusions:

Mandatory reporting makes PCC useful for tracking CO poisoning in NYC, but incomplete reporting and challenges in distinguishing between confirmed and suspected cases limit its utility. Simultaneous tracking of the systems we evaluated can best reveal surveillance patterns.
Development of a Formalized, Multifaceted Mentorship Program in Physical Medicine and Rehabilitation Residency Education
Authors: Liang Jason , Kempenaar Ainsley , Sequeira Nicholas , Becker Lisa
Published: August 2021

Mentorship in medicine has long been a vital component to the training, development, and career advancement of physicians. Although optimal strategies for facilitating mentorship relationships are unknown, it is recognized that establishing a formalized mentorship program within residency training may augment mentor-mentee pairing, improve overall trainee experience, and enhance resident perception of strong mentoring relationships. A formalized mentorship program was successfully developed in a Canadian physical medicine and rehabilitation residency program, including innovations such as near-peer self-matching, a needs assessment survey, a speed dating event, formation of “link groups,” and “fireside chats” with faculty members. This approach may serve as a guide for other medical education and residency programs seeking to implement a similar concept.
Prevalence of Advanced HIV Disease, Cryptococcal Antigenemia, and Suboptimal Clinical Outcomes Among Those Enrolled in Care in Vietnam
Authors: Dat Vu Quoc , Lyss Sheryl , Dung Nguyen Thi Hoai , Hung Le Manh , Pals Sherri L. , Anh Ho Thi Van , Kinh Nguyen Van , Bateganya Moses
Published: August 2021

Background:

People living with advanced HIV disease are at high risk of morbidity and mortality. We assessed the prevalence of cryptococcal antigenemia (CrAg) and clinical outcomes among patients newly presenting with CD4 ≤100 cells/μL in Vietnam.

Setting:

Twenty-two public HIV clinics in Vietnam.

Methods:

During August 2015–March 2017, antiretroviral therapy (ART)-naïve adults presenting for care with CD4 ≤100 cells/μL were screened for CrAg. Those who consented to study enrollment were followed up for up to 12 months and assessed for clinical outcomes.

Results:

Of 3504 patients with CD4 results, 1354 (38.6%) had CD4 ≤100 cells/μL, of whom 1177 (86.9%) enrolled in the study. The median age was 35 years (interquartile range 30–40); 872 (74.1%) of them were men, and 892 (75.8%) had CD4 <50 cells/μL. Thirty-six patients (3.1%) were CrAg-positive. Overall, 1151 (97.8%) including all who were CrAg-positive initiated ART. Of 881 patients (76.5%) followed up for ≥12 months, 623 (70.7%) were still alive and on ART at 12 months, 54 (6.1%) had transferred to nonstudy clinics, 86 (9.8%) were lost to follow-up, and 104 (11.8%) had died. Among all 1177 study participants, 143 (12.1%) died, most of them (123, 86.0%) before or within 6 months of enrollment. Twenty-seven patients (18.9%) died of pulmonary tuberculosis, 23 (16.1%) died of extrapulmonary tuberculosis, 8 (5.6%) died of Talaromyces marneffei infection, and 6 (4.2%) died of opioid overdose. Eight deaths (5.8%) occurred among the 36 CrAg-positive individuals.

Conclusions:

Late presentation for HIV care was common. The high mortality after entry in care calls for strengthening of the management of advanced HIV disease.
The Implications of Same-Day Discharge After Primary Unilateral Cleft Lip Repair: A National Surgical Quality Improvement Program-Based Study
Authors: Jain Nirbhay S. , Cronin Brendan J. , Liu Mengyuan T. , Lee Justine C.
Published: August 2021

Introduction:

Orofacial clefts are the most common craniofacial anomaly observed in the United States. Permitted by recent advancements in anesthesia and multimodal pain management, there has been a trend toward outpatient cleft lip repair to alleviate hospital burden and minimize healthcare costs. The purpose of this study was to compare complication rates between outpatient and inpatient cleft lip repair from large national samples as well as identify preoperative factors that predicted discharge status.

Methods:

The National Surgical Quality Improvement Program database for pediatrics was used to analyze 30-day outcomes for all patients undergoing cleft lip repair (CPT (current procedural terminology) code 40700) from 2012 to 2019. Complication rates were compared across 3 groups: same day discharge, next day discharge, and later discharge. Preoperative factors, including comorbidities and demographics, were analyzed to determine the impact of discharge date on complications as well as identify independent predictors of discharge timing and perioperative complications.

Results:

A total of 6689 patients underwent primary cleft lip repair, with 16.8% discharging on day of surgery, and 72.4% discharging 1 day after surgery. Complication rates were statistically equivalent between same day and next day discharge. Preoperative factors predicting complication and postoperative admission included age <6 months and weight less than ten pounds at the time of surgery. Patients discharged after more than 1 day in the hospital had higher rates of complications as well as more preoperative comorbidities.

Conclusions:

Complication rates between same day and next day discharge are equivalent, suggesting that same day discharge is a safe option in select patients. Clinical judgment is critical in making these decisions
Intercostal nerve cryoablation during surgical stabilization of rib fractures
Authors: Choi Jeff , Min Jung Gi , Jopling Jeffrey K. , Meshkin Sean , Bessoff Kovi E. , Forrester Joseph D.
Published: August 2021

BACKGROUND

Intercostal nerve cryoablation (IC) offers potential for targeted and durable analgesia for patients with traumatic rib fractures. Our pilot study aimed to investigate thoracoscopic IC's safety, feasibility, and preliminary efficacy for patients undergoing surgical stabilization of rib fractures (SSRF). We hypothesized that concurrent surgical stabilization of rib fractures and intercostal nerve cryoablation (SSRF-IC) is a safe and feasible procedure without immediate or long-term complications.

METHODS

We retrospectively evaluated patients 18 years or older who underwent SSRF (with or without IC) for acute rib fractures at our level I trauma center between September 1, 2019, and September 30, 2020. We performed IC under thoracoscopic visualization (−70°C for 2 minutes per intercostal nerve bundle). Among patients whose only operative procedure during hospitalization was SSRF, we evaluated post-SSRF length of stay, operative times, opioid requirements (oral morphine equivalents), and pain scores (Numerical Rating Scale). Generalized estimating equations compared SSRF and SSRF-IC group outcomes (population mean [robust standard error]). We assessed long-term outcomes of patients who underwent SSRF-IC.

RESULTS

Thirty-four patients (144 ribs) underwent SSRF; of these, 20 patients (135 ribs) underwent SSRF-IC. Patients who did and did not undergo concurrent IC had no significant difference demographic, injury, or hospitalization characteristics. Among 20 patients who did not undergo other operations, 12 underwent SSRF-IC. We did not find significant difference between SSRF and SSRF-IC groups' median operative times or post-SSRF length of stay. Compared with SSRF group, SSRF-IC group did not have statistically significant change in pain score (0.2 [1.5] lower) or opioid use (43.9 [86.1] mg/d greater) between 12 hours before SSRF and last 24 admission hours. Among 17 SSRF-IC patients who followed-up postdischarge (median [range], 160 [9–357] days), one reported mild chest wall paresthesia; no other complications were reported.

CONCLUSION

This pilot study performing 135 intercostal nerve cryoablations on 20 patients suggests that IC is safe and feasible for patients undergoing SSRF. Evaluating IC's analgesic efficacy for rib fractures requires further study.

LEVEL OF EVIDENCE

Therapeutic, Level V.
HLA Loci and Recurrence of Focal Segmental Glomerulosclerosis in Pediatric Kidney Transplantation
Authors: Shaw Brian I. , Ochoa Alejandro , Chan Cliburn , Nobuhara Chloe , Gbadegesin Rasheed , Jackson Annette M. , Chambers Eileen T.
Published: August 2021

Background.

Recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation accounts for the majority of allograft failures in children with primary FSGS. Although current research focuses on FSGS pathophysiology, a common etiology and mechanisms of disease recurrence remain elusive.

Methods.

We performed a retrospective review of the Scientific Registry of Transplant Recipients to determine the association of specific HLA recurrence of FSGS. Kidney transplants recipients under the age of 19 who were diagnosed with FSGS, who were transplanted after January 1, 2000, and who had complete HLA data were included in the study. We performed simple logistic regression on all HLA A, B, C, DR, and DQ represented in the dataset and FSGS recurrence and then determined those associated with recurrence using the Benjamini–Hochberg method for multiple comparisons. For those HLAs that were associated with recurrence, we further determined the effect of matching recipient and donor HLA with recurrence.

Results.

HLA DR7, DR53, DQ2, DR52, and DQ7 were associated with increased or decreased risk of recurrent disease after transplantation. We identified a risk haplotype consisting of HLA-DR7, DR53, and DQ2 that was consistently associated with an increased risk of recurrence (odds ratio 1.91; 95% confidence interval, 1.44-2.54, P < 0.001). We also found that donor/recipient concordance for HLA-DQ7 was associated with a decreased risk of recurrence (odds ratio 0.42; 95% confidence interval, 0.37-0.53, P = 0.009).

Conclusions.

HLA profiles may be used for risk stratification of recurrence of FSGS in pediatric kidney transplant recipients and deserves further study.
Predicting COVID-19 Incidences from Patients’ Viral Load using Deep-Learning
Authors: Khalil Athar , Handawi Khalil Al , Chamseddine Ibrahim , Mohsen Zeina , Nour Afif Abdel , Feghali Rita , Kokkolaras Michael
Published: August 2021

The transmission of the contagious COVID-19 is known to be highly dependent on individual viral dynamics. Since the cycle threshold (Ct) is the only semi-quantitative viral measurement that could reflect infectivity, we utilized Ct values to forecast COVID-19 incidences. Our COVID-19 cohort (n=9531), retrieved from a single representative cross-sectional virology test center in Lebanon, revealed that low daily mean Ct values are followed by an increase in the number of national positive COVID-19 cases. A subset of the data was used to develop a deep neural network model, tune its hyperparameters, and optimize the weights for minimal mean square error of prediction. The final model’s accuracy is reported by comparing its predictions with an unseen dataset. Our model was the first to capture the interaction of the previously reported Ct values with the upcoming number of COVID-19 cases and any temporal effects that arise from population dynamics. Our model was deployed as a publicly available and easy-to-use estimator to facilitate prospective validation. Our model has potential application in predicting COVID-19 incidences in other countries and in assessing post-vaccination policies. Aside from emphasizing patient responsibility in adopting early testing practices, this study proposed and validated viral load measurement as a rigid input that can enhance outcomes and precision of viral disease predicting models.
Global disparities in SARS-CoV-2 genomic surveillance
Authors: Brito Anderson F. , Semenova Elizaveta , Dudas Gytis , Hassler Gabriel W. , Kalinich Chaney C. , Kraemer Moritz U.G. , Ho Joses , Tegally Houriiyah , Githinji George , Agoti Charles N. , Matkin Lucy E. , Whittaker Charles ,   Danish Covid-19 Genome Consortium,   COVID-19 Impact Project,   Network for Genomic Surveillance in South Africa (NGS-SA),   GISAID core curation team, Howden Benjamin P , Sintchenko Vitali , Zuckerman Neta S. , Mor Orna , Blankenship Heather M , Oliveira Tulio de , Lin Raymond T. P. , Siqueira Marilda Mendonça , Resende Paola Cristina , Vasconcelos Ana Tereza R. , Spilki Fernando R. , Aguiar Renato Santana , Alexiev Ivailo , Ivanov Ivan N. , Philipova Ivva , Carrington Christine V. F. , Sahadeo Nikita S. D. , Gurry Céline , Maurer-Stroh Sebastian , Naidoo Dhamari , von Eije Karin J , Perkins Mark D. , Kerkhove Maria van , Hill Sarah C. , Sabino Ester C. , Pybus Oliver G. , Dye Christopher , Bhatt Samir , Flaxman Seth , Suchard Marc A. , Grubaugh Nathan D. , Baele Guy , Faria Nuno R.
Published: August 2021

Genomic sequencing provides critical information to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments and vaccines, and guide public health responses. To investigate the spatiotemporal heterogeneity in the global SARS-CoV-2 genomic surveillance, we estimated the impact of sequencing intensity and turnaround times (TAT) on variant detection in 167 countries. Most countries submit genomes >21 days after sample collection, and 77% of low and middle income countries sequenced <0.5% of their cases. We found that sequencing at least 0.5% of the cases, with a TAT <21 days, could be a benchmark for SARS-CoV-2 genomic surveillance efforts. Socioeconomic inequalities substantially impact our ability to quickly detect SARS-CoV-2 variants, and undermine the global pandemic preparedness.

One-Sentence Summary

Socioeconomic inequalities impacted the SARS-CoV-2 genomic surveillance, and undermined the global pandemic preparedness.
Anti–GM-CSF autoantibodies promote a “pre-diseased” state in Crohn’s Disease
Authors: Mortha Arthur , Remark Romain , Del Valle Diane Marie , Chuang Ling-Shiang , Chai Zhi , Alves Inês , Azevedo Catarina , Gaifem Joana , Martin Jerome , Tuballes Kevin , Barcessat Vanessa , Tai Siu Ling , Huang Hsin-Hui , Laface Ilaria , Jerez Yeray Arteaga , Boschetti Gilles , Villaverde Nicole , Wang Mona D. , Korie Ujunwa M. , Murray Joseph , Choung Rok-Seon , Sato Takahiro , Laird Renee M. , Plevy Scot , Rahman Adeeb , Torres Joana , Porter Chad , Riddle Mark S. , Kenigsberg Ephraim , Pinho Salomé S. , Cho Judy H. , Merad Miriam , Colombel Jean-Frederic , Gnjatic Sacha
Published: August 2021

Background & Aims

Anti–GM-CSF autoantibodies (aGMAb) are detected in ileal Crohn’s Disease (CD) patients. Their induction and mode of action impacting homeostasis during, or prior to disease are not well understood. We aimed to investigate the underlying mechanisms leading to the induction of aGMAb, from functional orientation to recognized epitopes, for their impact on intestinal immune homeostasis and use as predictive biomarker for complicated CD.

Methods

Using longitudinally collected sera from active component US personnel, we characterize naturally occurring aGMAb in a subset of CD patients years before disease onset. We employed biochemical, cellular, and transcriptional analysis to uncover a mechanism that governs the impaired immune balance in CD years prior to diagnosis.

Results

Neutralizing aGMAb are specific to posttranslational glycosylations on GM-CSF, detectable years prior to diagnosis, and associated with complicated CD at presentation. Glycosylation and production of GM-CSF change in CD patients, altering myeloid homeostasis and destabilizing group 3 innate lymphoid cells. Perturbations in immune homeostasis precede the inflammation and are detectable in the non-inflamed CD mucosa of patients presenting with anti-GM-CSF autoantibodies.

Conclusions

Anti-GM-CSF autoantibodies predict the diagnosis of complicated CD, have unique epitopes, and impair myeloid cell homeostasis across the ILC3-GM-CSF-myeloid cell axis, altering intestinal immune homeostasis long before the diagnosis of disease.
Epidemiology of the use of inferior vena cava filters in Brazil between 2008 and 2019
Authors: Louzada Andressa Cristina Sposato , Leiderman Dafne Braga Diamante , da Silva Marcelo Fiorelli Alexandrino , Portugal Maria Fernanda Cassino , de Campos Guerra João Carlos , Teivelis Marcelo Passos , Wolosker Nelson
Published: August 2021

Purpose

to study the totality of inferior vena cava filters placed in the Brazilian Public Health System, which insures more than 160 million Brazilians, trends by geographic region and in-hospital deaths after filter placements and also due to pulmonary embolism between 2008 and 2019.

Patients and methods

public and open data regarding in-hospital mortality due to pulmonary embolism and all inferior vena cava filters placed in Brazilian public hospitals between January 2008 and December 2019 were extracted from the Brazilian Public Health System’s databases.

Results

9108 inferior vena cava filters were placed, 98.18% of which was therapeutic. There was an overall increasing use of these devices, statistically significant for all Brazilian regions, except the North. In-hospital mortality rate in patients who received inferior vena cava filters was 6.21%, stable over time. We observed an upward trend in in-hospital mortality rate due to pulmonary embolism, statistically significant for all Brazilian regions, except the North.

Conclusion

We observed a low standardized rate of inferior vena cava filter placements in Brazil between 2008 and 2019, but with a trend towards an increasing trend use. Almost all indications for filter placement were therapeutic. In hospital mortality in patients receiving inferior vena cava filters was high, 6.21%, and stable over time, whereas the trend of in-hospital mortality rate due to pulmonary embolism is increasing. Our findings were heterogeneous across Brazilian regions and contrasted to those observed in the USA, which is likely due to cultural and socioeconomic factors.
Motor Learning in Response to Different Experimental Pain Models among Healthy Individuals: A Systematic Review
Authors: Izadi Mohammad , Franklin Sae , Bellafiore Marianna , Franklin David W.
Published: August 2021

Learning new movement patterns is a normal part of daily life, but of critical importance in both sport and rehabilitation. A major question is how different sensory signals are integrated together to give rise to motor adaptation and learning. More specifically, there is growing evidence that pain can give rise to alterations in the learning process. Despite a number of studies investigating the role of pain on the learning process, there is still no systematic review to summarize and critically assess investigations regarding this topic in the literature. Here in this systematic review, we summarize and critically evaluate studies that examined the influence of experimental pain on motor learning. Seventeen studies that exclusively assessed the effect of experimental pain models on motor learning among healthy individuals were included for this systematic review, carried out based on the PRISMA statement. The results of the review revealed there is no consensus regarding the effect of pain on the skill learning acquisition and retention. However, several studies demonstrated that participants who experienced pain continued to express a changed motor strategy to perform a motor task even one week after training under the pain condition. The results highlight a need for further studies in this area of research, and specifically to investigate whether pain has different effects on motor learning depending on the type of motor task.
L-citrulline ameliorates pathophysiology in a rat model of superimposed preeclampsia
Authors: Man Andy W. C. , Zhou Yawen , Lam Uyen D. P. , Reifenberg Gisela , Werner Anke , Habermeier Alice , Closs Ellen I. , Daiber Andreas , Münzel Thomas , Xia Ning , Li Huige
Published: August 2021

Preeclampsia, characterized by hypertension, proteinuria, and fetal growth restriction, is one of the leading causes of maternal and perinatal mortality. By far, there is no effective pharmacological therapy for preeclampsia. The present study was conducted to investigate the effects of L-citrulline supplementation in Dahl salt-sensitive rat, a model of superimposed preeclampsia. Parental DSSR were treated with L-citrulline (2.5 g/L in drinking water) from the day of mating to the end of lactation period. Blood pressure of the rats was monitored throughout pregnancy and markers of preeclampsia were assessed. Endothelial function of the pregnant DSSR was assessed by wire myograph. L-citrulline supplementation significantly reduced gestational hypertension, proteinuria, and levels of circulating soluble fms-like tyrosine kinase 1 in DSSR. L-citrulline improved maternal endothelial function by augmenting the production of nitric oxide in the aorta and improving endothelium-derived hyperpolarizing factor-mediated vasorelaxation in resistance arteries. L-citrulline supplementation improved placental insufficiency and fetal growth, which were associated with an enhancement of angiogenesis and reduction of fibrosis and senescence in the placentas. In addition, L-citrulline downregulated genes involved in the toll-like receptor 4 and nuclear factor-κB signaling pathway. In conclusion, this study shows that L-citrulline supplementation reduces gestational hypertension, improves placentation and fetal growth in a rat model of superimposed preeclampsia. L-citrulline supplementation may represent an effective and safe therapeutic strategy for preeclampsia that benefit both the mother and the fetus.
Global network structure and local transcriptomic vulnerability shape atrophy in sporadic and genetic behavioral variant frontotemporal dementia
Authors: Shafiei Golia , Bazinet Vincent , Dadar Mahsa , Manera Ana L. , Collins D. Louis , Dagher Alain , Borroni Barbara , Sanchez-Valle Raquel , Moreno Fermin , Laforce Robert , Graff Caroline , Synofzik Matthis , Galimberti Daniela , Rowe James B. , Masellis Mario , Tartaglia Maria Carmela , Finger Elizabeth , Vandenberghe Rik , de Mendonça Alexandre , Tagliavini Fabrizio , Santana Isabel , Butler Chris , Gerhard Alex , Danek Adrian , Levin Johannes , Otto Markus , Sorbi Sandro , Jiskoot Lize C. , Seelaar Harro , van Swieten John C. , Rohrer Jonathan D. , Mišić Bratislav , Ducharme Simon ,   Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI),   GENetic Frontotemporal dementia Initiative (GENFI)
Published: August 2021

Connections among brain regions allow pathological perturbations to spread from a single source region to multiple regions. Patterns of neurodegeneration in multiple diseases, including behavioral variant of frontotemporal dementia (bvFTD), resemble the large-scale functional systems, but how bvFTD-related atrophy patterns relate to structural network organization remains unknown. Here we investigate whether neurodegeneration patterns in sporadic and genetic bvFTD are conditioned by connectome architecture. Regional atrophy patterns were estimated in both genetic bvFTD (75 patients, 247 controls) and sporadic bvFTD (70 patients, 123 controls). We first identify distributed atrophy patterns in bvFTD, mainly targeting areas associated with the limbic intrinsic network and insular cytoarchitectonic class. Regional atrophy was significantly correlated with atrophy of structurally- and functionally-connected neighbors, demonstrating that network structure shapes atrophy patterns. The anterior insula was identified as the predominant group epicenter of brain atrophy using data-driven and simulation-based methods, with some secondary regions in frontal ventromedial and anteromedial temporal areas. Finally, we find that FTD-related genes, namely C9orf72 and TARDBP, confer local transcriptomic vulnerability to the disease, effectively modulating the propagation of pathology through the connectome. Collectively, our results demonstrate that atrophy patterns in sporadic and genetic bvFTD are jointly shaped by global connectome architecture and local transcriptomic vulnerability.
High temporal resolution RNA-seq time course data reveals mammalian lncRNA activation mirrors neighbouring protein-coding genes
Authors: Muskovic Walter , Slavich Eve , Maslen Ben , Kaczorowski Dominik C. , Cursons Joseph , Crampin Edmund , Kavallaris Maria
Published: August 2021

Background

The advent of next-generation sequencing revealed extensive transcription beyond protein-coding genes, identifying tens of thousands of long non-coding RNAs (lncRNAs). Selected functional examples raised the possibility that lncRNAs, as a class, may maintain broad regulatory roles. Compellingly, lncRNA expression is strongly linked with adjacent protein-coding gene expression, suggesting a potential cis-regulatory function. Evidence for these regulatory roles may be obtained through careful examination of the precise timing of lncRNA expression relative to adjacent protein-coding genes.

Results

Where causal cis-regulatory relationships exist, lncRNA activation is expected to precede changes in adjacent target gene expression. Using an RNA-seq time course of uniquely high temporal resolution, we profiled the expression dynamics of several thousand lncRNAs and protein-coding genes in synchronized, transitioning human cells. Our findings reveal lncRNAs are expressed synchronously with adjacent protein-coding genes. Analysis of lipopolysaccharide-activated mouse dendritic cells revealed the same temporal relationship observed in transitioning human cells.

Conclusion

Our findings suggest broad-scale cis-regulatory roles for lncRNAs are not common. The strong association between lncRNAs and adjacent genes may instead indicate an origin as transcriptional by-products from active protein-coding gene promoters and enhancers.
Elys deficiency constrains Kras-driven tumour burden by amplifying oncogenic stress
Authors: Morgan Kimberly J , Doggett Karen , Geng Fan-Suo , Whitehead Lachlan , Smith Kelly A , Hogan Benjamin M , Simons Cas , Baillie Gregory J , Molania Ramyar , Papenfuss Anthony T , Hall Thomas E , Ober Elke A , Stainier Didier Y R , Gong Zhiyuan , Heath Joan K
Published: August 2021

The nucleoporin ELYS, encoded by AHCTF1, is a large multifunctional protein with essential roles in nuclear pore assembly and mitosis. Using a zebrafish model of hepatocellular carcinoma, in which the expression of an inducible mutant kras transgene (krasG12V) drives hepatocyte-specific hyperplasia and liver enlargement, we show that reducing ahctf1 gene dosage by 50% markedly shrinks tumour burden, while non-hyperplastic tissues are unaffected. We demonstrate that ahctf1 heterozygosity impairs nuclear pore formation, mitotic spindle assembly and chromosome segregation, leading to DNA damage and activation of TP53-dependent and independent mechanisms of cell death and cell cycle arrest. This selective vulnerability of cancer cells to mild disruption of Elys function uncovers a novel synthetic lethal interaction between ahctf1 and kras mutations that could be exploited therapeutically. Heterozygous expression of both ahctf1 and ranbp2, or treatment of heterozygous ahctf1 larvae with the nucleocytoplasmic transport inhibitor, Selinexor, completely blocked krasG12V-driven hepatocyte hyperplasia, revealing promising avenues for combinatorial treatments.
An intranasal OMV-based vaccine induces high mucosal and systemic protecting immunity against a SARS-CoV-2 infection
Authors: van der Ley Peter A. , Zariri Afshin , van Riet Elly , Oosterhoff Dinja , Kruiswijk Corine P.
Published: August 2021

The development of more effective, accessible and easy to administer COVID-19 vaccines next to the currently marketed mRNA, viral vector and whole inactivated virus vaccines, is essential to curtain the SARS-CoV-2 pandemic. A major concern is reduced vaccine-induced immune protection to emerging variants, and therefore booster vaccinations to broaden and strengthen the immune response might be required. Currently, all registered COVID-19 vaccines and the majority of COVID-19 vaccines in development are intramuscularly administered, targeting the induction of systemic immunity. Intranasal vaccines have the capacity to induce local mucosal immunity as well, thereby targeting the primary route of viral entry of SARS-CoV-2 with the potential of blocking transmission. Furthermore, intranasal vaccines offer greater practicality in terms of cost and ease of administration. Currently, only eight out of 112 vaccines in clinical development are administered intranasally. We developed an intranasal COVID-19 subunit vaccine, based on a recombinant, six proline stabilized, D614G spike protein (mC-Spike) of SARS-CoV-2 linked via the LPS-binding peptide sequence mCramp (mC) to Outer Membrane Vesicles (OMVs) from Neisseria meningitidis. The spike protein was produced in CHO cells and after linking to the OMVs, the OMV-mC-Spike vaccine was administered to mice and Syrian hamsters via intranasal or intramuscular prime-boost vaccinations. In all animals that received OMV-mC-Spike, serum neutralizing antibodies were induced upon vaccination. Importantly, high levels of spike-binding immunoglobulin G (IgG) and A (IgA) antibodies in the nose and lungs were only detected in intranasally vaccinated animals, whereas intramuscular vaccination only induced an IgG response in the serum. Two weeks after their second vaccination hamsters challenged with SARS-CoV-2 were protected from weight loss and viral replication in the lungs compared to the control groups vaccinated with OMV or spike alone. Histopathology showed no lesions in lungs seven days after challenge in OMV-mC-Spike vaccinated hamsters, whereas the control groups did show pathological lesions in the lung. The OMV-mC-Spike candidate vaccine data are very promising and support further development of this novel non-replicating, needle-free, subunit vaccine concept for clinical testing.
Genomic drivers of large B-cell lymphoma resistance to CD19 CAR-T therapy
Authors: Jain Michael D. , Ziccheddu Bachisio , Coughlin Caroline A. , Faramand Rawan , Griswold Anthony J. , Reid Kayla M , Landgren Ola , Locke Frederick L. , Maura Francesco , Davila Marco L. , Schatz Jonathan H.
Published: August 2021

Chimeric antigen receptor-reprogrammed autologous T cells directed to CD19 are breakthrough immunotherapies for heavily pretreated patients with aggressive B-cell lymphomas but still fail to cure most patients. Host inflammatory and tumor microenvironmental factors associate with CAR-19 resistance, but the tumor-intrinsic factors underlying these phenomena remain undefined. To characterize genomic drivers of resistance, we interrogated whole genome sequencing of 30 tumor samples from 28 uniformly CAR-19-treated large-cell lymphoma patients. We reveal that patterns of genomic complexity (i.e., chromothripsis and APOBEC mutational activity), and distinct genomic alterations (deletions of RB1 or RHOA) associate with more exhausted immune microenvironments and poor outcome after CAR-19 therapy. Strikingly, pretreatment reduced expression or sub-clonal mutation of CD19 did not affect responses, suggesting CAR-19 therapy successes are due not only to direct antigen-dependent cytotoxicity but require surmounting immune exhaustion in tumor microenvironments to permit broader host responses that eliminate tumors.
Rapid gene evolution in an ancient post-transcriptional and translational regulatory system compensates for meiotic X chromosomal inactivation
Authors: Xia Shengqian , Ventura Iuri M. , Blaha Andreas , Sgromo Annamaria , Han Shuaibo , Izaurralde Elisa , Long Manyuan
Published: August 2021

It is conventionally assumed that conserved pathways evolve slowly with little participation of gene evolution. Nevertheless, it has been recently observed that young genes can take over fundamental functions in essential biological processes, for example, development and reproduction. It is unclear how newly duplicated genes are integrated into ancestral networks and reshape the conserved pathways of important functions. Here, we investigated origination and function of two autosomal genes that evolved recently in Drosophila: Poseidon and Zeus, which were created by RNA-based duplications from the X-linked CAF40, a subunit of the conserved CCR4-NOT deadenylase complex involved in post-transcriptional and translational regulation. Knockdown and knockout assays show that the two genes quickly evolved critically important functions in viability and male fertility. Moreover, our transcriptome analysis demonstrates that the three genes have a broad and distinct effect in the expression of hundreds of genes, with almost half of the differentially expressed genes being perturbed exclusively by one paralog, but not the others. Co-immunoprecipitation and tethering assays show that the CAF40 paralog Poseidon maintains the ability to interact with the CCR4-NOT deadenylase complex and might act in post-transcriptional mRNA regulation. The rapid gene evolution in the ancient post-transcriptional and translational regulatory system may be driven by evolution of sex chromosomes to compensate for the meiotic X chromosomal inactivation (MXCI) in Drosophila.
Expression variations in Ectodysplasin-A gene (eda) may contribute to morphological divergence of scales in Haplochromine cichlids
Authors: Wagner Maximilian , Bračun Sandra , Duenser Anna , Sturmbauer Christian , Gessl Wolfgang , Ahi Ehsan Pashay
Published: August 2021

Background

Elasmoid scales are one of the most common dermal appendages and can be found in almost all species of bony fish differing greatly in their shape. Whilst the genetic underpinnings behind elasmoid scale development have been investigated, not much is known about the mechanisms involved in the shaping of scales. To investigate the links between gene expression differences and morphological divergence, we inferred shape variation of scales from two different areas of the body (anterior and posterior) stemming from ten haplochromine cichlid species from different origins (Lake Tanganyika, Lake Malawi, Lake Victoria and riverine). Additionally, we investigated transcriptional differences of a set of genes known to be involved in scale development and morphogenesis in fish.

Results

We found that scales from the anterior and posterior part of the body strongly differ in their overall shape, and a separate look on scales from each body part revealed similar trajectories of shape differences considering the lake origin of single investigated species. Above all, nine as well as 11 out of 16 target genes showed expression differences between the lakes for the anterior and posterior dataset, respectively. Whereas in posterior scales four genes (dlx5, eda, rankl and shh) revealed significant correlations between expression and morphological differentiation, in anterior scales only one gene (eda) showed such a correlation. Furthermore, eda displayed the most significant expression difference between species of Lake Tanganyika and species of the other two younger lakes. Finally, we found genetic differences in downstream regions of eda gene (e.g. in the eda-tnfsf13b inter-genic region) that are associated with observed expression differences. This is reminiscent of a genetic difference in the eda-tnfsf13b inter-genic region which leads to gain or loss of armour plates in stickleback.

Conclusion

These findings provide evidence for cross-species transcriptional differences of an important morphogenetic factor, eda, which is involved in formation of ectodermal appendages. These expression differences appeared to be associated with morphological differences observed in the scales of haplochromine cichlids indicating potential role of eda mediated signal in divergent scale morphogenesis in fish.