bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise, headache, and factors associated with headache in chronic whiplash
Authors: Landén Ludvigsson Maria , Peterson Gunnel , Widh Simon , Peolsson Anneli
Published: November 2019

Background:

Almost 40% of individuals with chronic whiplash-associated disorders (WAD) report headache after 5 years, making it one of the most common persistent symptoms besides neck pain, but randomized treatment studies are lacking. This study aimed to evaluate the effect of 3 different exercise approaches on headache in chronic WAD grades 2 and 3, and to identify potential factors associated with such headache, and whether they differ depending on 3 different aspects of such headache (current headache, maximum headache, or headache bothersomeness).

Methods:

This was an analysis of a randomized clinical trial of people with chronic WAD and headache (n = 188), who were randomized to either 12 weeks of neck-specific exercise without (NSE) or with a behavioral approach (NSEB) or physical activity prescription (PPA). Data were collected at baseline and at 3, 6, and 12 months. Physical and psychosocial factors were tested for association with headache. Multivariate regression models and linear mixed models were used.

Results:

The NSE/NSEB groups reported reduced headache both over time and compared to PPA. Up to 51% (NSE) and 61% (NSEB) reported at least 50% reduction in their headache at 12 months. The PPA group was not improved over time. Neck pain and dizziness were associated with headache regardless of aspect of headache. The only associated psychosocial factor was anxiety, which was associated with headache bothersomeness. Other factors were mainly physical, and up to 51% of the variance was explained.

Conclusion:

Headache in chronic WAD, may be reduced with neck-specific exercise with or without a behavioral approach. Chronic headache was associated with neck pain and dizziness regardless of aspect tested. Other factors associated with headache in chronic WAD were mainly physical rather than psychosocial.

Trial registration number:

Clinical Trials.gov, no: NCT015285
Are safe guards at trampoline parks safe enough?
Authors: Lee Jae Eun , Kim Ju Hyun , Park Chan Hee , Gwak Dae Won , Kim Chul-Hyun , Park Donghwi , Hwang Jong-Moon
Published: November 2019

Rationale:

Recently, commercial indoor trampoline parks have been opened around the globe, and both the number of venues and the park users are increasing. Academic literatures have largely focused on home trampoline related injuries, and less is known about the injuries associated with trampoline parks due to the limited number of studies or cases reported. In this report, we present a complete spinal cord injury sustained at a commercial indoor trampoline park.

Patient Concerns:

A 26-year old male developed tetraplegia after plainly jumping on the trampolines and diving into one of the foam pits head first.

Diagnosis:

C-spine CT revealed bilateral interfacetal dislocation on C6-7, and his C-spine MRI showed anterior translational injury at C6-7 with severe cord encroachment and complete discoligamentous complex disruption. He was diagnosed with complete spinal cord injury.

Interventions:

The patient underwent 30 minutes each of physical therapy and occupational therapy twice a day for a total of 25 days of in-patient rehabilitation. Interventions included tilt table, passive range of motion exercises, functional electrical stimulation, sitting balance training, upper extremity strengthening exercise, and hand manipulation exercises.

Outcome:

Despite intensive rehabilitation and the patient's good spirit, there was no functional change in all physical examinations between evaluations at initial and at discharge.

Lessons:

In conclusion, we aim to alert the risks associated with improper use of trampolines, promote safer entertainment environment, and aid in developing mandatory safety measures. We hope to alert the risks associated with improper use of trampolines, promote safer entertainment environment, and aid in developing mandatory safety measures.
Contemporary full-mouth rehabilitation using a digital smile design in combination with conventional and computer-aided design/manufacturing restorative materials in a patient with bruxism
Authors: Lee Jae-Hyun , Kim Sung-Hun , Han Jung-Suk , Yeo In-Sung Luke , Yoon Hyung-In
Published: November 2019

Rationale:

Full-mouth rehabilitation of patients with bruxism and severely worn dentition poses a great challenge to clinicians. Several treatment planning methods and restorative materials are used to treat tooth wear in modern dentistry. Clinicians should be able to select the most suitable treatment planning methods and materials for individual patients depending on their specific situation.

Patient concerns:

A 47-year-old male was referred for evaluation of a severely worn dentition.

Diagnoses:

Clinical and radiographic evaluation revealed tooth wear in the entire dentition. The interocclusal distance at rest was 4 mm, and the patient had a parafunctional habit of bruxism.

Interventions:

A digital smile design was used to formulate a treatment plan. Full-mouth rehabilitation was performed using a combination of conventional and digital materials and methods.

Outcomes:

The full-mouth restoration showed satisfactory functions and esthetics. No complications were observed in the restorations, supporting tissues, and temporomandibular joints during 2-year follow-up.

Lessons:

In clinical practice, it is important to determine the optimal combination of the available methods for treatment planning. This case report details the formulation of a unique treatment plan for the dental rehabilitation of a severely worn out dentition, which is considered challenging due to the limitations imposed by biological tissues and restorative materials. The use of conventional and digital tools for treatment planning, patient education, and treatment execution was demonstrated.
Acute mental change as the presenting sign of posthepatectomy hepatic failure
Authors: Chon Jin Young , Moon Hye Young , Han Sangbin , Kwak Jueun , Lee Ji Young , Kim Eun Sung , Chung Hyun Sik
Published: November 2019

Rationale:

Hepatectomy is a treatment to increase survival and curability of patients with intrahepatic lesions or malignant tumors. However, posthepatectomy liver failure (PHLF) can occur. This case is a patient showing acute mental change in postanesthetic care unit (PACU) as an uncommon symptom of PHLF after extended right hepatectomy.

Patient concerns:

A 68-year-old male patient was admitted for surgery of Klatskin tumor. He had hypertension and atrial fibrillation. His model for end-stage liver disease score was 16 pts. His serum bilirubin and ammonia levels were 4.75 mg/dL and 132.8 mcg/dL, respectively. Other laboratory data were nonspecific. He underwent extended right hepatic lobectomy including segments IV-VIII for 9 hours. Weight of liver specimen was 1028 g which was about 58% of total liver volume based on computed tomographic volumetry. The patient was extubated and moved to the PACU with stable vital sign and regular self-breathing. He could obey verbal commands. Fifteen minutes after admission to the PACU, the patient showed abruptly decreasing mental status and self-breathing.

Diagnoses:

Brain computed tomography, blood culture, and sputum culture were performed to diagnose brain lesions and sepsis for evaluating the sudden onset comatous mental status. Results showed nonspecific finding.

Interventions:

He was intubated for securing airway and applying ventilatory care. The patient was moved to the intensive care unit. He received intensive conservative therapy including continuous renal replacement therapy and broad-spectrum antibiotics.

Outcomes:

The patient's condition was worsened. He expired on postoperative day 3.

Lessons:

Acute mental change is uncommon and rare as initial symptoms of PHLF. Therefore, clinician may overlook the diagnosis of PHLF in patients with acute mental change after hepatectomy. Thus, clinician should plan an aggressive treatment for PHLF including liver transplantation by recognizing any suspicious symptom, although such symptom is rare.
Tonic–clonic seizure during the ultrasound-guided stellate ganglion block because of an injection into an unrecognized variant vertebral artery
Authors: Lu Fan , Tian Jie , Dong Jifu , Zhang Kexian
Published: November 2019

Rationale:

Recent years have witnessed a marked improvement in the safety and accuracy of nerve blocks with the help of ultrasound and other visualization technologies. This study reports a challenging case of a severe complication during the ultrasound-guided stellate ganglion block.

Patient concerns:

A 28-year-old male patient with refractory migraine complained episodic pulsatile pain with photophobia, haphalgesia of the scalp for 3 years.

Interventions:

Ultrasound-guided stellate ganglion block with 4 ml of 1% lidocaine was administrated.

Outcomes:

A sudden loss of consciousness and tonic–clonic seizure was occurred after negative aspiration and test dose. Further sonographic examination revealed a variation in the left vertebral artery, which remained unrecognized during the needle insertion because of its sliding ability under the differential pressure applied by the probe.

Lessons:

Inadvertent intra-arterial injection of a local anesthetic agent could be minimized under the ultrasound guidance with various protective strategies, including the determination of any prior variation, optimizing the block route, maintaining a constant probe pressure, and using saline for the test dosage. This case resulted in the implementation of new protocols of the ultrasound-guided stellate ganglion block in our department.
Sinus of Valsalva aneurysm protruding into the mitral anterior leaflet causing dyspnea
Authors: Wang Baogang , Ma Dashi , Qu Limei , Cao Dianbo , Man Xiaxia
Published: November 2019

Introduction:

Sinus of Valsalva aneurysm (SVA) protruding into the mitral anterior leaflet is an extremely rare clinical condition; herein, we present a case of unruptured noncoronary SVA protruding into the mitral anterior leaflet.

Patient's concerns:

A 46-year-old male was referred to hospital for exertional dyspnea.

Diagnosis:

Transthoracic echocardiography (TTE) and coronary computed tomography angiography (CTA) suggested a noncoronary SVA protruding into the mitral anterior leaflet, causing mitral regurgitation and aortic insufficiency.

Interventions:

The aneurysm was resected and the aortic and mitral valves were replaced with mechanical valves via a transaortic approach.

Outcomes:

Postoperative recovery was uneventful.

Conclusions:

A rare noncoronary SVA protruding into the mitral anterior leaflet can be diagnosed via TTE and CTA. Transaortic mitral surgery is feasible in patients with a dilated aortic annulus ring and mitral valve diseases
Association between iron metabolism and cognitive impairment in older non-alcoholic fatty liver disease individuals
Authors: Xu Jing , Sun Weihao , Yang Li
Published: November 2019

Sparse is the research on the relationship between iron metabolism and mild cognitive impairment (MCI) in adults aged over 60 years with non-alcoholic fatty liver disease (NAFLD). The soluble transferrin receptor (sTfR), serum iron (SI), serum ferritin (SF), transferrin (TRF) and hemoglobin (HB) are indicators of iron metabolism.

This study examined whether iron metabolism is associated with cognitive impairment in older individuals.

A cross-sectional study was held in patients from a Chinese center. Individuals with NAFLD aged over 60 years were included if they did not have excessive alcohol intake and were free of stroke or dementia. Their cognitive function was assessed by the same neurologist. 3.0T H proton magnetic resonance spectroscopy (1H-MRS) was performed to evaluate the hippocampus of the participants without contraindication. t test and Chi-square test were used to analyze the data. Binary logistic regression was used for correlation analysis.

Fifty four (54%) of participants were diagnosed with MCI by the psychiatrist. MCI was significantly associated with higher sTfR after adjustment of all the covariates (OR = 2.565, 95%CI: 1.334∼4.934; P = .005). No statistically significant associations were observed between MCI and age or blood glucose or choline (Cho) /creatine (Cr) of theright hippocampus head.

Increased age and low levels of sTfR and HB were associated with MCI in NAFLD individuals aged over 60 years.
Endovascular stent repair of celiac arterial aneurysm
Authors: Xia Feng-Fei , Fan Zhen-Qiang , Huo Xiao-Bing , Fu Yu-Fei , Xu Yuan-Shun
Published: November 2019

The aim of this study was to evaluate the safety and clinical effectiveness of endovascular stent repair of celiac arterial aneurysm (CAA).

From January 2015 to December 2018, 11 patients (7 males, 4 females with a mean age of 52.2 ± 7.9 years) underwent endovascular stent repair of CAA in our center. A covered stent was used to occlude the CAA neck. Follow-up was performed 2 weeks and 1, 3, 6, and 12 months following surgery and yearly thereafter. Rates of technical success, treatment-related complications, and long-term outcome were analyzed.

Each patient was placed with 1 stent for repair of CAA. Stent was placed in the celiac and common hepatic arteries for 10 patients and was placed in the celiac artery for 1 patient. The duration of the procedure ranged from 50 to 75 minutes (mean 63.2 ± 7.2 minutes). The rate of technical success of the endovascular stent repair was 100%. No patient experienced CAA rupture or instant endoleak during or after stent insertion. Abdominal pain was relieved progressively after stent insertion. All patients were followed-up for 6 to 48 months (mean 22.4 ± 10.8 months). All patients were alive during the follow-up. No endoleaks were experienced during follow-up with 100% stent patency rate. No patient suffered splenic, hepatic, or bowel infarction during follow-up.

Endovascular stent repair is a safe, simple, and effective treatment for patients with CAA.
A no-reference respiratory blur estimation index in nuclear medicine for image quality assessment
Authors: Morland David , Lalire Paul , Guendouzen Sofiane , Papathanassiou Dimitri , Passat Nicolas
Published: November 2019

Few indexes are available for nuclear medicine image quality assessment, particularly for respiratory blur assessment. A variety of methods for the identification of blur parameters has been proposed in literature mostly for photographic pictures but these methods suffer from a high sensitivity to noise, making them unsuitable to evaluate nuclear medicine images. In this paper, we aim to calibrate and test a new blur index to assess image quality.

Blur index calibration was evaluated by numerical simulation for various lesions size and intensity of uptake. Calibrated blur index was then tested on gamma-camera phantom acquisitions, PET phantom acquisitions and real-patient PET images and compared to human visual evaluation.

For an optimal filter parameter of 9, non-weighted and weighted blur index led to an automated classification close to the human one in phantom experiments and identified each time the sharpest image in all the 40 datasets of 4 images. Weighted blur index was significantly correlated to human classification (ρ = 0.69 [0.45;0.84] P < .001) when used on patient PET acquisitions.

The provided index allows to objectively characterize the respiratory blur in nuclear medicine acquisition, whether in planar or tomographic images and might be useful in respiratory gating applications.
Comparison of postoperative axial stability of intraocular lens and capsulotomy parameters between precision pulse capsulotomy and continuous curvilinear capsulotomy
Authors: Bang Seung Pil , Jun Jong Hwa
Published: November 2019

Objectives:

The aim of this study was to verify the safety and stability of precision pulse capsulotomy (PPC) by comparison of the axial stability of the intraocular lens (IOL) and the capsulotomy parameters during 6 months of follow-up after cataract surgery using PPC or the conventional method (continuous curvilinear capsulorhexis, CCC).

Design:

Prospective observational study.

Setting:

Tertiary referral center.

Subjects:

Fifty nine eyes of 59 candidates for cataract surgery.

Interventions:

PPC (33 eyes) or CCC (26 eyes).

Outcome measures:

The anterior capsule opacification grade and effective lens position (ELP) were measured 1 week and 1, 3, and 6 months postoperatively.

Results:

No significant difference in the mean anterior capsule opacification grade or the effective lens position was found between the PPC and CCC groups at any time point; however, the standard deviation and root mean square of the effective lens position were significantly lower in the PPC group than in the CCC group during follow-up (P = .002 and P = .011, respectively). There was a significantly lower discrepancy between the intended vs achieved capsulotomy area and better circularity in the PPC group than in the CCC group at all time points.

Conclusions:

The overall variability in effective lens position was less when cataract surgery was performed using PPC than when performed using CCC. Circularity was better and had a more predictable size with PPC than with CCC.
Pleural small cell carcinoma with massive pleural effusion
Authors: Jang Jong Geol , Jang Min Hye , Ahn June Hong
Published: November 2019

Rationale:

Small cell carcinoma (SCC) occurs mostly in the lung, and small cell lung cancer accounts for 13% of newly diagnosed lung cancers. Only 2.5% of SCC occurs in extrapulmonary sites, and SCC of pleural origin is especially very uncommon.

Patient concerns:

An 85-year-old man presenting with progressive dyspnea for more than 7 days.

Diagnoses:

Computed tomography scan of the chest showed massive pleural effusion and diffuse nodular thickening of the pleura on the right chest. Sonography-guided needle biopsy of the pleural mass was performed and histologic and immunohistochemical findings revealed SCC. Since no parenchymal lung lesion was observed, the patient was finally diagnosed with SCC of the pleura (SCCP).

Interventions:

Due to the patient's old age and poor performance status, chemotherapy was not performed and only drainage of pleural effusion was conducted for symptom relief.

Outcomes:

Dyspnea improved after pleural effusion drainage. The patient was discharged and transferred to a local medical center for hospice care.

Lessons:

Although primary SCCP is extremely rare, SCCP should also be considered as well as mesothelioma in case of presence of a pleural-based mass with massive pleural effusion.
Substance Use and Sexual Risk Behavior Among Male and Transgender Women Sex Workers at the Prostitution Outreach Center in Amsterdam, the Netherlands
Authors: Drückler Susanne , van Rooijen Martijn S. , de Vries Henry J.C.
Published: November 2019

Objectives

Male and transgender women sex workers (TSWs) are vulnerable for sexually transmitted infections (STIs) and human immunodeficiency virus (HIV), and substance use might be a relevant contributing factor. We assessed sociodemographic characteristics and substance use among sex workers; divided into 3 groups: Transgender women sex workers, male sex workers who have sex with men only or also with females (MSW-M), male sex workers who have sex with females only (MSW-F).

Methods

A survey on substance use and sexual (risk) behavior was offered during routine STI screening at the Prostitution and Health Centre (P&G292) in Amsterdam. Bacterial STI positivity (chlamydia (including lymphogranuloma venereum), gonorrhea, and/or infectious syphilis), and substance use were compared (χ2 test, Fisher exact test).

Results

From 2014 until 2015, 99 (60.4%) of 164 eligible visitors participated (n = 69 MSW-M [69.7%], n = 15 TSW [15.2%], and n = 15 MSW-F [15.2%]). Transgender women sex workers reported the highest number of sex partners in the previous 6 months (median: MSW-M 60 vs. TSW 300 vs. MSW-F 12; P < 0.001). The 3 groups did not differ in having condomless anal or oral sex. Bacterial STI positivity was 29.0% in MSW-M, 26.7% in TSW, and 13.3% in MSW-F (P = 0.56). Three new HIV infections were diagnosed, all in MSW-M, whereas 20.3% of MSW-M and 20.0% of TSW were known HIV-positive compared with none of MSW-F (P = 0.14). Illicit substance use during working time in <6 months was 40.5% among MSW-M, 40.0% among TSW, and 20.0% among MSW-F (P = 0.02). The most reported reason for substance use was: “sex work becomes physically easier.”

Conclusions

Bacterial STI positivity and illicit substances use during work were high in all 3 sex worker groups, emphasizing the importance of combined and targeted interventions. In-depth qualitative research is needed to better understand intentions and reasons for substance use.
Follow the Sex: Influence of Network Structure on the Effectiveness and Cost-Effectiveness of Partner Management Strategies for Sexually Transmitted Infection Control
Authors: Kao Szu-Yu Zoe , Enns Eva A.
Published: November 2019

Background

It is well established that network structure strongly influences infectious disease dynamics. However, little is known about how the network structure impacts the cost-effectiveness of disease control strategies. We evaluated partner management strategies to address bacterial sexually transmitted infections (STIs) as a case study to explore the influence of the network structure on the optimal disease management strategy.

Methods

We simulated a hypothetical bacterial STI spread through 4 representative network structures: random, community-structured, scale-free, and empirical. We simulated disease outcomes (prevalence, incidence, total infected person-months) and cost-effectiveness of 4 partner management strategies in each network structure: routine STI screening alone (no partner management), partner notification, expedited partner therapy, and contact tracing. We determined the optimal partner management strategy following a cost-effectiveness framework and varied key compliance parameters of partner management in sensitivity analysis.

Results

For the same average number of contacts and disease parameters in our setting, community-structured networks had the lowest incidence, prevalence, and total infected person-months, whereas scale-free networks had the highest without partner management. The highly connected individuals were more likely to be reinfected in scale-free networks than in the other network structures. The cost-effective partner management strategy depended on the network structures, the compliance in partner management, the willingness-to-pay threshold, and the rate of external force of infection.

Conclusions

Our findings suggest that contact network structure matters in determining the optimal disease control strategy in infectious diseases. Information on a population's contact network structure may be valuable for informing optimal investment of limited resources.
Aminotransferase Ratio Is a Useful Index for Hepatosteatosis in Children and Adolescents
Authors: Lu Cheng-Wei , Lin Ming-Shyan , Lin Yu-Sheng , Chang I-Jen , Tsai Ming-Horng , Wei Kuo-Liang , Chen Mei-Yen
Published: November 2019

Nonalcoholic fatty liver disease (NAFLD) and childhood obesity are emerging global health issues. The aim of this study was to identify a simple predictor of NAFLD in children and adolescents. This community-based study was conducted from December 2012 to September 2013 in Taiwan and included 1,222 children between 10 and 19 years of age. After excluding alcohol consumption and hepatic-related lesions, NAFLD was diagnosed according to sonographic criteria. Potential confounding factors (including age, gender, and anthropometric and laboratory data) were tested by logistic regression analysis. The cutoff value was determined using receiver operating characteristic (ROC) curve analysis. In addition to older age, heavier weight, and wider waist, subjects with NAFLD had significantly higher blood pressure, lipid disturbances, and alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratios. The correlation between NAFLD and ALT/AST ratio remained significant even after adjusting for confounders (adjusted odds ratio [OR], 2.19; 95% confidence interval [CI], 1.24–3.87; p = .007). The risk score of having a fatty liver, based on ALT/AST ratio, was greater than 0.981 according to ROC curve analysis (sensitivity, 60.5%; specificity, 80.3%; area under the curve, 0.756; CI, 0.71–0.80; p < .001). Therefore, ALT/AST ratio may represent a powerful index of hepatosteatosis in children and adolescents.
Physiology, clinical evidence and diagnostic relevance of sound-induced and vibration-induced vestibular stimulation
Authors: Curthoys Ian S. , Dlugaiczyk Julia
Published: November 2019

Purpose of review

To examine the recent literature concerning the neural basis and clinical evidence for the response of the labyrinth to sound and vibration: vestibular-evoked myogenic potentials (VEMPs) and vibration-induced nystagmus (VIN).

Recent findings

There are two streams of information from each otolith – a sustained stream (afferents with regular resting activity, signalling gravity and low-frequency linear accelerations) and a transient stream (afferents with irregular resting activity) signalling onset of linear acceleration, and sound and vibration. These irregular neurons are synchronized to each cycle of the stimulus. Neurons in the transient stream are tested by presenting sounds or vibration (500 Hz) and using surface electrodes to measure myogenic potentials from muscles activated by otolithic stimuli (VEMPs). 100 Hz vibration activates irregular canal afferents and causes a stimulus-locked VIN in patients with asymmetric canal function. These new tests of the transient system have one big advantage over older tests of the sustained system – they reliably show the effect of long-term unilateral vestibular loss.

The new physiological and anatomical evidence shows how sound and vibration activate otolith and canal receptors and so provides the scientific foundation for VEMPs and VIN, which are important tools for diagnosing vestibular disorders.

Video abstract

http://links.lww.com/CONR/A47.
Eye movements in demyelinating, autoimmune and metabolic disorders
Authors: Kattah Jorge C. , Zee David S.
Published: November 2019

Purpose of review

In the last three decades, the use of eye movements and vestibular testing in many neurological disorders has accelerated, primarily because of practical technologic developments. Although the acute vestibular syndrome is a prime example of this progress, more chronic neurologic and systemic disorders have received less attention. We focus here on recent contributions relating vestibular and ocular motor abnormalities in inflammatory, demyelinating, metabolic, and peripheral nervous system disorders

Recent findings

Vestibular abnormalities have been identified in acute demyelinating neuropathies (AIDP), in novel genetic mutations responsible for CANVAS (cerebellar ataxia, neuropathy vestibular areflexia syndrome), and in other inherited neuropathies (variants of Charcot-Marie-Tooth disease). In addition, there are differentiating characteristics between the most common CNS demyelinating disorders: multiple sclerosis and neuromyelitis optica (NMO). We summarize new information on Vitamin D metabolism in benign paroxysmal positional vertigo (BPPV), followed by a brief review of the vestibular and ocular motor findings in Wernicke's encephalopathy. We conclude with findings in several paraneoplastic/autoimmune disorders.

This literature review highlights the impact of a careful vestibular and ocular motor evaluation in common neurologic disorder, not only for the initial diagnosis but also for monitoring disease and rehabilitation. A careful examination of eye movements and vestibular function, supplemented with new video techniques to quantify the findings, should be part of the standard neurologic examination.
Interpretable AI for beat-to-beat cardiac function assessment
Authors: Ouyang David , He Bryan , Ghorbani Amirata , Langlotz Curt P. , Heidenreich Paul A. , Harrington Robert A. , Liang David H. , Ashley Euan A. , Zou James Y.
Published: November 2019

Accurate assessment of cardiac function is crucial for diagnosing cardiovascular disease1, screening for cardiotoxicity2,3, and deciding clinical management in patients with critical illness4. However human assessment of cardiac function focuses on a limited sampling of cardiac cycles and has significant interobserver variability despite years of training2,5,6. To overcome this challenge, we present the first beat-to-beat deep learning algorithm that surpasses human expert performance in the critical tasks of segmenting the left ventricle, estimating ejection fraction, and assessing cardiomyopathy. Trained on echocardiogram videos, our model accurately segments the left ventricle with a Dice Similarity Coefficient of 0.92, predicts ejection fraction with mean absolute error of 4.1%, and reliably classifies heart failure with reduced ejection fraction (AUC of 0.97). Prospective evaluation with repeated human measurements confirms that our model has less variance than experts. By leveraging information across multiple cardiac cycles, our model can identify subtle changes in ejection fraction, is more reproducible than human evaluation, and lays the foundation for precise diagnosis of cardiovascular disease. As a new resource to promote further innovation, we also make publicly available one of the largest medical video dataset of over 10,000 annotated echocardiograms.

Key Points

Video based deep learning evaluation of cardiac ultrasound accurately identifies cardiomyopathy and predict ejection fraction, the most common metric of cardiac function.

Using human tracings obtained during standard clinical workflow, deep learning semantic segmentation accurately labels the left ventricle frame-by-frame, including in frames without prior human annotation.

Computational cardiac function analysis allows for beat-by-beat assessment of ejection fraction, which more accurately assesses cardiac function in patients with atrial fibrillation, arrhythmias, and heart rate variability.
Phoenix Enhancer: proteomics data mining using clustered spectra
Authors: Bai Mingze , Qin Chunyuan , Shu Kunxian , Griss Johannes , Perez-Riverol Yasset , Zhu Weimin , Hermjakob Henning
Published: November 2019

Motivation

Spectrum clustering has been used to enhance proteomics data analysis: some originally unidentified spectra can potentially be identified and individual peptides can be evaluated to find potential mis-identifications by using clusters of identified spectra. The Phoenix Enhancer provides an infrastructure to analyze tandem mass spectra and the corresponding peptides in the context of previously identified public data. Based on PRIDE Cluster data and a newly developed pipeline, four functionalities are provided: i) evaluate the original peptide identifications in an individual dataset, to find low confidence peptide spectrum matches (PSMs) which could correspond to mis-identifications; ii) provide confidence scores for all originally identified PSMs, to help users evaluate their quality (complementary to getting a global false discovery rate); iii) identify potential new PSMs for originally unidentified spectra; and iv) provide a collection of browsing and visualization tools to analyze and export the results. In addition to the web based service, the code is open-source and easy to re-deploy on local computers using Docker containers.

Availability

The service of Phoenix Enhancer is available at http://enhancer.ncpsb.org. All source code is freely available in GitHub (https://github.com/phoenix-cluster/) and can be deployed in the Cloud and HPC architectures.

Contact

baimz@cqupt.edu.cn

Supplementary information

Supplementary data are available online.
Expanded huntingtin CAG repeats disrupt the balance between neural progenitor expansion and differentiation in human cerebral organoids
Authors: Zhang Jinqiu , Ooi Jolene , Utami Kagistia Hana , Langley Sarah R. , Aning Obed Akwasi , Park Dong Shin , Renner Magdalena , Ma Shiming , Cheok Chit Fang , Knoblich Juergen A. , Ginhoux Florent , Petretto Enrico , Pouladi Mahmoud A.
Published: November 2019

Huntington disease (HD) manifests in both adult and juvenile forms. Mutant HTT gene carriers are thought to undergo normal brain development followed by a degenerative phase, resulting in progressive clinical manifestations. However, recent studies in children and prodromal individuals at risk for HD have raised the possibility of abnormal neurodevelopment. Although key findings in rodent models support this notion, direct evidence in the context of human physiology remains lacking. Using a panel of isogenic HD human embryonic pluripotent stem cells and cerebral organoids, we investigated the impact of mutant HTT on early neurodevelopment. We find that ventricular zone-like neuroepithelial progenitor layer expansion is blunted in an HTT CAG repeat length-dependent manner due to premature neurogenesis in HD cerebral organoids, driven by cell intrinsic processes. Transcriptional profiling and imaging analysis revealed impaired cell cycle regulatory processes, increased G1 length, and increased asymmetric division of apical progenitors, collectively contributing to premature neuronal differentiation. We demonstrate increased activity of the ATM-p53 pathway, an up-stream regulator of cell cycle processes, and show that treatment with ATM antagonists partially rescues the blunted neuroepithelial progenitor expansion in HD organoids. Our findings suggest that CAG repeat length regulates the balance between neural progenitor expansion and differentiation during early neurodevelopment. Our results further support the view that HD, at least in its early-onset forms, may not be a purely neurodegenerative disorder, and that abnormal neurodevelopment may be a component of HD pathophysiology.
A one-step biofunctionalization strategy of electrospun scaffolds enables spatially selective presentation of biological cues
Authors: Wieringa Paul , Girao Andre , Truckenmuller Roman , Welle Alexander , Micera Silvestro , van Wezel Richard , Moroni Lorenzo
Published: November 2019

To recapitulate the heterogeneous complexity of tissues in our body with synthetic mimics of the extracellular matrix (ECM), it is important to develop methods that can easily allow the selective functionalization of defined spatial domains. Here, we introduce a facile method to functionalize microfibrillar meshes with different reactive groups able to bind biological moieties in a one-step reaction. The resulting scaffolds proved to selectively support a differential neurite growth after being seeded with dorsal root ganglia. Considering the general principles behind the method developed, this is a promising strategy to realize enhanced biomimicry of native ECM for different regenerative medicine applications.
Self-Organization of Whole Gene Expression through Coordinated Chromatin Structural Transition: Validation of Self-Organized Critical Control of Genome Expression
Authors: Zimatore Giovanna , Tsuchiya Masa , Hashimoto Midori , Kasperski Andrzej , Giuliani Alessandro
Published: November 2019

Through our studies on whole genome regulation, we have demonstrated the existence of self-organized critical control (SOC) of whole gene expression - genomic self-organization mechanism through the emergence of a critical point (CP) at both the cell population and single cell level. In this paper, based on HRG and EGF-stimulated MCF-7 breast-cancer cell line, we shed light on the origin of critical transitions stemming from coordinated chromatin remodeling. In so doing, we validated the core of the SOC control mechanism through the application of a non-linear signal analysis technique (Recurrence Quantification Analysis: RQA), and of Principal Component Analysis (PCA). The main findings were:

Transcriptional co-regulation follows a strong and invariant exponential decay as between gene spacing along the chromosome is increased. This shows that the co-regulation occurs on a mainly positional basis reflecting local chromatin organization.

There are two main fluctuation modes on the top of the cell-kind specific gene expression values spanning the entire genome expression. These modes establish an autonomous genomic critical control system (genome-engine) through the activation of the CP for cell-fate guiding critical transitions revealed by SOC analysis.

The elucidation of the link between spatial position on chromosome and co-regulation together with the identification of specific locations on the genome devoted to the generalization of perturbation stimuli, give a molecular basis to the self-organization dynamics of genome expression and cell-fate decision.
Accumulation of 137Cs in Insects - Herpetobiont Integuments
Authors: Monoshyn D. , Rudchenko L. , Shupova T. , Gaychenko V.
Published: November 2019

The study of the radioactivity of insects - herpetobiont elytra that belong to different trophic groups shown the presence of incorporated 137Cs, there were concentrated about 20% of total animal radioactivity. The comparison of the radionuclide comparison was done in both dried and fresh samples. Radioactive contamination of integument comes mainly from the terminal phase of metamorphosis (at the ninth phase).
Neural substrates of working memory updating
Authors: Nir-Cohen Gal , Kessler Yoav , Egner Tobias
Published: November 2019

Working memory (WM) needs to protect current content from interference and simultaneously be amenable to rapid updating with newly relevant information. An influential model suggests these opposing requirements are met via a basal ganglia (BG) - thalamus gating mechanism that allows for selective updating of prefrontal cortex (PFC) WM representations. A large neuroimaging literature supports the general involvement of the PFC, BG, and thalamus, as well as posterior parietal cortex (PPC), in WM. However, the specific functional contributions of these regions to key sub-processes of WM updating, namely gate-opening, content substitution, and gate closing, are still unknown, as common WM tasks conflate these processes. We therefore combined functional MRI with the reference-back task, specifically designed to tease apart these sub-processes. Participants compared externally presented face stimuli to a reference face held in WM, while alternating between updating and maintaining this reference, resulting in opening vs. closing the gate to WM. Gate opening and substitution processes were associated with strong BG, thalamic and fronto-parietal activation, but – intriguingly - the same activity profile was observed for sensory cortex supporting task stimulus processing (i.e., the fusiform face area). In contrast, gate closing was not reliably associated with any of these regions. These findings provide new support for the involvement of the BG in gate opening as suggested by the gating model, but qualify the model’s assumptions by demonstrating that gate closing does not seem to depend on the BG, and that gate opening also involves task-relevant sensory cortex.
CrkL is required for donor T cell migration to GvHD Target organs
Authors: Roy Nathan H. , Mammadli Mahinbanu , Burkhardt Janis K. , Karimi Mobin
Published: November 2019

The success of cancer therapies based on allogeneic hematopoietic stem cell transplant relies on the ability to separate graft-versus-host disease (GvHD) from graft-versus-tumor (GVT) responses. Controlling donor T cell migration into peripheral tissues is a viable option to limit unwanted tissue damage, but a lack of specific targets limits progress on this front. Here, we show that the adaptor protein CrkL, but not the closely related family members CrkI or CrkII, is a crucial regulator of T cell migration.In vitro, CrkL-deficient T cells fail to polymerize actin in response to the integrin ligand ICAM-1, resulting in defective migration. Using a mouse model of GvHD/GVT, we found that while CrkL-deficient T cells can efficiently eliminate hematopoietic tumors they are unable to migrate into inflamed organs, such as the liver and small intestine, and thus do not cause GvHD. These results suggest a specific role for CrkL in trafficking to peripheral organs but not the lymphatic system. In line with this, we found that although CrkL-deficient T cells could clear hematopoietic tumors, they failed to clear the same tumor growing subcutaneously, highlighting the role of CrkL in controlling T cell migration into peripheral tissues. Our results define a unique role for CrkL in controlling T cell migration, and suggest that CrkL function could be therapeutically targeted to enhance the efficacy of immunotherapies involving allogeneic donor cells.
Engineering transplantable jejunal mucosal grafts using primary patient-derived organoids from children with intestinal failure
Authors: Meran Laween , Massie Isobel , Weston Anne , Gaifulina Riana , Faull Peter , Orford Michael , Kucharska Anna , Baulies Anna , Hirst Elizabeth , Konig Julia , Tedeschi Alfonso Maria , Pellegata Alessandro Filippo , Eli Susanna , Snijders Ambrosius P. , Collinson Lucy , Thapar Nikhil , Thomas Geriant , Eaton Simon , Bonfanti Paola , De Coppi Paolo , Li Vivian S.W.
Published: November 2019

Intestinal failure (IF), following extensive anatomical or functional loss of small intestine (SI), has debilitating long-term effects on infants and children with this condition. Priority of care is to increase the child’s length of functional intestine, jejunum in particular, to improve nutritional independence. Here we report a robust protocol for reconstruction of autologous intestinal mucosal grafts using primary IF patient materials. Human jejunal intestinal organoids derived from paediatric IF patients can be expanded efficiently in vitro with region-specific markers preserved after long-term culture. Decellularized human intestinal matrix with intact ultrastructure is used as biological scaffolds. Proteomic and Raman spectroscopic analyses reveal highly analogous biochemical composition of decellularized human SI and colon matrix, implying that they can both be utilised as scaffolds for jejunal graft reconstruction. Indeed, seeding of primary human jejunal organoids to either SI or colonic scaffolds in vitro can efficiently reconstruct functional jejunal grafts with persistent disaccharidase activity as early as 4 days after seeding, which can further survive and mature after transplantation in vivo. Our findings pave the way towards regenerative medicine for IF patients.
High-Resolution Single-Cell 3D-Models of Chromatin Ensembles during Drosophila Embryogenesis
Authors: Sun Qiu , Perez-Rathke Alan , Czajkowsky Daniel M. , Shao Zhifeng , Liang Jie
Published: November 2019

Single-cell chromatin studies provide insights into how chromatin structure relates to functions of individual cells. However, balancing high-resolution and genome wide-coverage remains challenging. We describe a computational method for the reconstruction of large 3D-ensembles of single-cell (sc) chromatin conformations from population Hi-C that we apply to study embryogenesis inDrosophila. With minimal assumptions of physical properties and without adjustable parameters, our method generates large ensembles of chromatin conformations via deep-sampling. Our method identifies specific interactions, which constitute 5–6% of Hi-C frequencies, but surprisingly are sufficient to drive chromatin folding, giving rise to the observed Hi-C patterns. Modeled sc-chromatins quantify chromatin heterogeneity, revealing significant changes during embryogenesis. Furthermore,>50% of modeled sc-chromatin maintain topologically associating domains (TADs) in early embryos, when no population TADs are perceptible. Domain boundaries become fixated during development, with strong preference at binding-sites of insulator-complexes upon the mid-blastula transition. Overall, high-resolution 3D-ensembles of sc-chromatin conformations enable further in-depth interpretation of population Hi-C, improving understanding of the structure-function relationship of genome organization.
SPECC1L-deficient palate mesenchyme cells show speed and directionality defect
Authors: Goering Jeremy P. , Isai Dona Greta , Hall Everett G. , Wilson Nathan R. , Kosa Edina , Wenger Luke W. , Umar Zaid , Yousaf Abdul , Czirok Andras , Saadi Irfan
Published: November 2019

Clefts of the lip and/or palate (CL/P) are common anomalies that occur in 1/800 live births. Pathogenic SPECC1L variants identified in patients with rare atypical clefts and syndromic CL/P suggest the gene plays a primary role in face and palate development. We have generated Specc1l gene-trap (Specc1lcGT) and truncation (Specc1lΔC510) alleles that cause embryonic or perinatal lethality, respectively. Specc1lcGT/ΔC510 compound mutants show delayed and abnormal palatal shelf elevation at E14.5. By E15.5, the mutant shelves do elevate and fuse, however, the palatal rugae form abnormally. Palatogenesis requires extensive mesenchymal remodeling, especially during palatal shelf elevation. We posit that this remodeling involves collective movement of neural crest-derived palatal mesenchyme cells. Live time-lapse microscopy was performed to visualize in vitro wound-repair assays with wildtype and SPECC1L-deficient primary mouse embryonic palatal mesenchyme (MEPM) cells. SPECC1L-deficient MEPM cells consistently showed delayed closure in wound-repair assays. To evaluate which features of cellular movement were responsible, we performed automated particle image velocimetry (PIV) and manual cell tracking. The analyses revealed that both cell speed and directionality are disrupted in SPECC1L-deficient cells compared to controls. To determine if primary MEPM cells can move collectively, we assayed stream formation, which is a hallmark of collective movement. Indeed, MEPM cultures displayed correlated movement of neighboring cells. Importantly, correlation length was reduced in SPECC1L-deficient cultures, consistent with a role for SPECC1L in collective migration. Furthermore, we demonstrated that activation of the PI3K-AKT pathway with the 740Y-P small molecule can rescue the wound-closure delay in SPECC1L-deficient MEPM cells. Cell tracking analyses showed that this rescue was due to both increased speed and improved directionality. Altogether, our data showed a novel role for SPECC1L in guided movement through modulation of PI3K-AKT signaling.
Dynamic regulation of CD45 by tetraspanin CD53
Authors: Dunlock V. E. , Arp A. B. , Jansen E. , Charrin S. , van Deventer S. J. , Wright M. D. , Querol-Cano L. , Rubinstein E. , van Spriel A. B.
Published: November 2019

T cells are central to the adaptive immune response, playing a role in both the direct and indirect killing of pathogens and transformed cells. The activation of T cells is the result of a complex signaling cascade, initiated at the T cell receptor (TCR), and ending with the induction of proliferation. CD45, a member of the protein tyrosine phosphatase family, is one of the most abundant membrane proteins on T cells and functions by regulating activation directly downstream of the TCR. As a result of alternative splicing, CD45 can be expressed in multiple isoforms, naive T cells express the CD45RA isoform, while activated T cells gain expression of CD45RO, which has been proposed to increase signaling. Though the importance of CD45 in TCR signaling, proliferation and cytokine production is well established, little is known about the regulation of CD45 activity. We discovered that the immune-specific tetraspanin CD53 directly affects the stability and function of CD45RO in T cells.

We have identified CD53 as a T cell co-stimulatory molecule in primary human and murine cells. Furthermore, we have shown that the absence of CD53 leads to an altered CD45 isoform expression as a result of decreased CD45RO stability on the cell surface. This instability was accompanied by increased mobility as measured by FRAP.

Together, this indicates that CD53 functions as a stabilizer of CD45RO, and therefore as a positive regulator of TCR signaling at the T cell surface. Our data provides novel insight into the role of tetraspanins in the regulation of immune signaling and may provide a new avenue for the regulation of T cell signaling.