bluuebunny/crossref_metadata_2025 huggingface dataset:
Perihematomal edema surrounding spontaneous intracerebral hemorrhage by CT
Authors: Shulman Julie G. , Jara Hernan , Qureshi Muhammad M. , Lau Helena , Finn Brandon , Abbas Saleh , Cervantes-Arslanian Anna M. , Mercado Melissa , Greer David , Chapman Margaret , Mian Asim Z. , Takahashi Courtney E.
Published: July 2020

Perihematomal edema (PHE) surrounding intracerebral hemorrhage (ICH) may contribute to disease-associated morbidity. Before quantifying PHE's effects on morbidity, a fast, accurate, and reproducible method for measuring PHE volume is needed. The aim of this study is to demonstrate the use of a semiautomated dual clustering segmentation algorithm to generate PHE volumetrics on noncontrast computed tomography (CT) of the head and compare this technique to physicians’ manual calculations.

This is a single-center, retrospective imaging study that included head CTs performed from January 2008 to December 2014 on 154 patients with ICH. Subjects ≥ 18 years old who were admitted to the hospital with spontaneous ICH were included. Included subjects had head CTs performed upon admission and within 6 to 24 hours. Two neurologists, 2 neuroradiologists, and a computer program all calculated hemorrhage and PHE volumes. Inter-rater correlation was evaluated using 2 statistical methods: intraclass correlations (ICCs) and limits of agreement (LOA). Additionally, correlation between volumes was separately evaluated using Pearson correlation coefficient.

There was an excellent correlation between measurements performed by neurologists and neuroradiologists using ABC/2 for ICH (0.93) and PHE (0.78). There was a good correlation between measurements performed by neurologists using ABC/2 and the volume measurements generated by the algorithm for ICH (0.69) and PHE (0.70). There was a fair correlation between measurements performed by neuroradiologists using ABC/2 and volume measurements generated by the algorithm for ICH (0.47) and good correlation for PHE (0.73).

Although the ABC/2 method for measuring PHE is quick and practical, algorithms that do not assume ellipsoidal shape may be more accurate.
Bilateral cervical chondrocutaneous branchial remnants
Authors: Lee Han Shin , Kim Tae Han , Jang Jae Yool , Woo Jung Woo , Lee JinKwon , Jeong Sang Ho , Jung Eun Jung , An Hyo Jung , Park Taejin
Published: July 2020

Rationale:

Cervical chondrocutaneous branchial remnants are rare, benign, congenital anomalies, frequently seen bilaterally.

Patient concerns:

Here, we report the case of a 4-month-old female infant who presented with bilateral lower neck skin tag since birth.

Diagnosis and Interventions:

The patient underwent mass excision. The final pathological diagnosis was bilateral cervical chondrocutaneous branchial remnants with hyaline cartilage.

Outcomes:

No complications were observed after excision. One-year follow-up revealed no recurrence.

Lessons:

Bilateral chondrocutaneous branchial remnants are rare anomalies. They are often associated with cardiac or genitourinary abnormalities. Therefore, additional preoperative imaging of the abdomen and heart are recommended.
Chronic inflammatory demyelinating polyradiculoneuropathy relapse after mexiletine withdrawal in a patient with concomitant myotonia congenita
Authors: Portaro Simona , Biasini Fiammetta , Bramanti Placido , Naro Antonino , Calabrò Rocco Salvatore
Published: July 2020

Introduction:

we report on the first case of a woman affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and recessive myotonia congenita (MC), treated with mexiletine. We aimed at describing the possible role of mexiletine in CIDP management.

Patient Concerns:

A 44-year-old female affected by CIDP and MC, gained beneficial effects for CIDP symptoms (muscle weakness, cramps, and fatigue) and relapses, after mexiletine intake (200 mg twice a day). The patient presented with detrimental effects after mexiletine drop out, with a worsening of CIDP symptoms.

Interventions:

The patient reported a nearly complete remission of muscle stiffness and weakness up to 3 years since mexiletine intake. Then, she developed an allergic reaction with glottis edema, maybe related to mexiletine intake, as per emergency room doctors’ evaluation, who suggested withdrawing the drug.

Outcomes:

The patient significantly worsened after the medication drop out concerning both CIDP and MC symptoms.

Conclusion:

This is the first report on the association of CIDP and MC in the same patient. Such diseases may share some clinical symptoms related to a persistent sodium currents increase, which maybe due either to the over-expression of sodium channels following axonal damage due to demyelination or to the chloride channel genes mutations. This is the possible reason why mexiletine maybe promising to treat CIDP symptoms.
Exploring the efficacy and safety of herbal medicine on Korean obese women with or without metabolic syndrome risk factors
Authors: Ko Youme , Kim Hyun-Ju , Kim Hojun , Choi Jin-Bong , Kwon Young-Dal , Jung Won-Seok , Jang Bo-Hyoung , Kim NamKwen , Song Yun-Kyung , Ko Seong-Gyu
Published: July 2020

Background:

The prevalence of obesity among women is increasing. Obesity is associated with various metabolic syndromes; conventional treatments are limited and may induce serious adverse events due to polytherapy regimens. Currently, demands for complementary and alternative medicine that has a proven safety profile for the treatment of obesity with or without metabolic risk factors are increasing.

Our team of preclinical experts reported a significant anti-obesity effect of the Korean herbal medicine, Galgeun-tang (GGT). Thus, we designed this trial to explore the effects of GGT among obese women to accumulate optimal clinical evidence.

Obesity is not only a component of metabolic syndrome and a factor associated with an increased risk of cardiovascular disease but is also related to insulin resistance. Previous research has confirmed that an increasing body mass index is highly related with increased risk of metabolic syndrome among overweight and obese individuals. The effectiveness of the Korean medicine herbal formula, GGT on obesity has been previously reported. The objective of this study is to assess the efficacy and safety of GGT for weight loss among obese Korean women with or without high risk for metabolic syndrome.

Methods/design:

This study is a randomized, double-blinded, placebo-controlled, multi-center clinical trial. A total of 160 participants will be randomly distributed in 2 groups, the GGT group or the placebo group in a 1:1 ratio using a web-based randomization system. Each group will be administered GGT or placebo 3 times a day for 12 weeks. The primary endpoint is to assess the change in weight from baseline. The secondary endpoints are the following: the changes in body composition measurements, anthropomorphic measurements, obesity screening Laboratory tests, patient self-reported questionnaires, and economic evaluation outcomes. Adverse events will also be reported.

Discussion:

The findings of this study will confirm methodologies regarding the efficacy and safety of GGT for weight loss among obese Korean women with or without metabolic risk factors.
Clinical diagnosis and endoscopic analysis of 10 cases of intestinal tuberculosis
Authors: Lu Shuangshuang , Fu Jinjin , Guo Yongxin , Huang Jin
Published: July 2020

To analyze the clinical characteristics of intestinal tuberculosis (ITB), pay attention to the diagnostic value of endoscopy and mucosal biopsy, improve the recognition of atypical manifestations of ITB under endoscopy, and reduce misdiagnosis and missed diagnosis.

The clinical data of 10 patients who were hospitalized in Changzhou second people's Hospital and finally diagnosed as ITB from January 1, 2015 to present were analyzed retrospectively. The basic information, medical history, clinical manifestations and computed tomography (CT), endoscopy of the patients was analyzed retrospectively. The results of pathological examination were analyzed and sorted out.

Among the 10 patients, the ratio of male to female was 7:3, 10 (100%) had abdominal pain, 3 (30%) had diarrhea and 2 (20%) had bloody stool. The positive rate of tuberculosis T cell test was 75% (6/8), the diagnostic rate of chest high resolution CT was 60%, and the abnormal rate of abdominal high-resolution CT was 66.7% (6/9). Colonoscopy showed that the lesions mainly involved ileocecum (70%) and ascending colon (60%). Most of the lesions were intestinal stenosis (60%) and circular ulcer (50%). In a few cases, cold abscess (20%) and scar diverticulum (10%). Most of the pathological manifestations were granuloma formation and multinucleated giant cells (60%). The detection rate of caseous granuloma was 20%.

The general condition and clinical manifestations of patients with ITB are not specific. Endoscopy and mucosal biopsy are of great significance for its diagnosis. The clinical manifestations and endoscopy of some patients showed atypical signs. Therefore, the combination of multi-disciplinary team models and the enhancement of clinician's recognition of the characteristics of endoscopic examination of ITB can improve us the diagnosis level of ITB.
Comparison of cervical muscle activity and spinal curvatures in the sitting position with 3 different sloping seats
Authors: Yim JongEun , Park Junhyuck , Lohman Everett , Do KwangSun
Published: July 2020

Lumbar and pelvic alignment may have a huge impact on the posture of the spine and other parts. The aim of this study were to compare the spinal curvature of the cervical, thoracic, and lumbar spine and the muscle activity of the cervical erector spinae muscle, upper trapezius muscle, and thoracic erector spinae muscle when sitting at 3 different sloped, seating surfaces. A 10° wedge was used as the seating surface and we compared a forward sloping seat surface, a flat seating surface, and a rear sloping seat surface, in that order. Twenty healthy officers were recruited for this study. The subjects sat on the seat of 3 different slopes and watched a total of 3 videos, 10 minutes each. The rest time was 10 minutes. Subjects were photographed while viewing videos and muscle activity was measured. There were significant differences in cervical, thoracic, lumbar curvatures, and muscle activity in the 3 different sitting positions according to seat tilt (P < .05). Among the 3 slopes, the forward slope decreased forward head posture and cervical erector spinae muscle activity (P < .05). The activity of the cervical erector spinae muscle was 2.67% with a forward sloping seat, 5.45% with a flat sloping seat, and 6.77% with a rear sloping seat, revealing a significant difference (P < .05). This suggests that a forward sloping seat surface was effective in maintaining a neutral alignment of the spine, and this decreased the cervical spine erector muscle activity. Based on this result, equipment and chair development to incline seats forward may improve posture and health, and prevent chronic pain.
The efficacy of acupuncture for improving the side effects of COVID-19 western medicine treatments
Authors: Huang Kuei-Yu , Chang Ching-Hao , Hsu Chung-Hua
Published: July 2020

Background

Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease, which is pandemic, infectious, and high mortality. Many commonly discussed medications being used to treat COVID-19 are not without potentially harmful side effects such as heart, liver, kidney problems, or other clinical symptoms. Acupuncture is a nonpharmacological method. When a needle is inserted into an acupuncture point, traumatic physical stimulation occurs, and then the neuroendocrine immune regulation network is activated. This study aimed to evaluate the efficacy of acupuncture for improving the side effects of COVID-19 western medicine treatments.

Methods

From their inception to December 10, 2020, the following electronic databases will be searched to identify relevant studies: MEDLINE, PubMed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and the Chinese Biomedical Literature Database (CBM), without any language restrictions. Randomized controlled trials and credible clinical observations without randomization include patients diagnosed with COVID-19, and receiving western medicine treatments or acupuncture, with no restrictions on disease stage, age, sex, or ethnicity. Primary outcomes would be used to evaluate the mortality rate, C-reactive protein (CRP), creatine, troponin, liver enzymes (aspartate aminotransferase and alanine aminotransferase), blood pressure, clinical symptoms (including fever, fatigue, myalgia, cough, skin rash, nausea, vomiting, and diarrhea), and serum cytokine levels. Secondary outcome would be used to evaluate the adverse events of acupuncture. Risk of bias will be assessed by 2 review authors independently according to the guidelines set out in the Cochrane Handbook for Systematic Reviews of Interventions.

Discussion

This is the first to evaluate the efficacy of acupuncture for improving the side effects of COVID-19 western medicine treatments. A longer follow-up should be considered in future studies.

Conclusion

This systematic review and meta-analysis would provide evidence of acupuncture specifically focused on its effectiveness and safety for patients with COVID-19 western medications adverse effects.

Registration:

Registered in the PROSPERO database (CRD42020189494).
Genetic polymorphisms in serine protease inhibitor Kazal-type 5 and risk of atopic dermatitis
Authors: Li Yunling , Li Yin , Li Wei , Guo Xiaoxuan , Zhou Sha , Zheng Huiwen
Published: July 2020

Background:

This study aimed to investigate the role of serine protease inhibitor Kazal-type 5 (SPINK5) polymorphisms (Asn368Ser, Asp386Asn and Glu420Lys) and the risk of atopic dermatitis (AD).

Methods:

Studies associated with SPINK5 mutations and AD risk were searched from three databases, including PubMed, Embase, and Cochrane library, with a retrieval deadline of April 22, 2019. An odds ratio (OR) with a 95% confidence interval (95% CI) was chosen as the effect size. Egger's linear regression test was enrolled to assess the level of publication bias.

Results:

Overall, 6 studies met the inclusion criteria for meta-analysis. Significantly statistical differences were calculated between patients with AD and healthy individuals on Asn368Ser polymorphism in the allele model (G vs A: OR = 1.2643, 95% CI = 1.0666–1.4987, P = .0069), co-dominant model (GG vs AA: OR = 1.6609, 95% CI = 1.1736–2.3505, P = .0042; GA vs AA: OR = 1.5448, 95% CI = 1.1263–2.1189, P = .0070), and dominant model (GG+GA vs AA: OR = 1.5700, 95% CI = 1.1656–2.1146, P 
= .0030). However, no statistically significant difference was found in the recessive model for Asn368Ser and other genetic models for Asp386Asn and Glu420Lys (all P > .05). No significant publication bias was found.

Conclusion:

The SPINK5 Asn368Ser polymorphism may be a risk factor for AD.
Influence of Socioeconomic Bias on Emergency Medicine Resident Decision Making and Patient Care
Authors: Fasano Heather T. , McCarter Maggie S. J. , Simonis Jacquelyn M. , Hoelscher Gretchen L. , Bullard Mark J.
Published: July 2020

Introduction

Physician bias impacts clinical decision making, resulting in disparities in patient care. Most existing studies focus on sex and racial bias. This study aimed to investigate disparities in physician decision making among patients of varying socioeconomic status (SES).

Methods

Emergency medicine residents (n = 31) participated in 3 consecutive scenarios of similar disease acuity but with standardized patients of varying SES. Following the scenarios, residents met with a standardized participant acting as an attending physician for a handoff to recount their decision-making processes and care recommendations. Blinded raters evaluated clinical performance using an objective assessment tool. We assessed associations between patient SES and resident-ordered imaging, ordered medication, patient-perceived empathy, and clinical performance. We used qualitative analyses to study residents' decision-making processes.

Results

Quantitative analyses revealed no significant relationship between SES and resident-ordered imaging, ordered medications, patient-perceived empathy, and clinical performance. Qualitative analyses revealed 3 themes regarding clinical decision making: (1) overt diagnostic focus, (2) discharge planning, and (3) risk and exposure.

Conclusions

Although quantitative analyses showed that SES did not affect clinical behavior within simulated scenarios, qualitative analyses uncovered 3 themes believed important to physician decision-making processes. Overt diagnostic focus may have resulted from the study environment in addition to organizational factors, policies, and training. Discharge planning, which was not explicitly studied, was often tailored to SES with emphasis placed on risks for patients of low SES. Further research is needed to uncover the nuances of bias, SES, and physician decision making throughout the patient care continuum and within various clinical environments.
Establishing a Cost-Effective 3-Dimensional Printing Laboratory for Anatomical Modeling and Simulation
Authors: Clifton William , Damon Aaron , Nottmeier Eric , Pichelmann Mark
Published: July 2020

Summary Statement

Three-dimensional (3D) printing is rapidly growing in popularity for anatomical modeling and simulation for medical organizations across the world. Although this technology provides a powerful means of creating accurately representative models of anatomic structures, there remains formidable financial and workforce barriers to understanding the fundamentals of technology use, as well as establishing a cost- and time-effective system for standardized incorporation into a workflow for simulator design and anatomical modeling. There are many factors to consider when choosing the appropriate printer and accompanying software to succeed in accomplishing the desired goals of the executing team. The authors have successfully used open-access software and desktop fused deposition modeling 3D printing methods to produce more than 1000 models for anatomical modeling and procedural simulation in a cost-effective manner. It is our aim to share our experience and thought processes of implementing 3D printing into our anatomical modeling and simulation workflow to encourage other institutions to comfortably adopt this technology into their daily routines.
Colon Involvement in Necrotizing Pancreatitis
Authors: Maatman Thomas K. , Nicolas Megan E. , Roch Alexandra M. , Lewellen Kyle A. , Al-Azzawi Hayder H. , Ceppa Eugene P. , House Michael G. , Nakeeb Attila , Schmidt Christian M. , Zyromski Nicholas J.
Published: July 2020

Objective:

To investigate the incidence, risk factors, and outcomes of colon involvement in patients with necrotizing pancreatitis.

Summary/Background Data:

Necrotizing pancreatitis is characterized by a profound inflammatory response with local and systemic implications. Mesocolic involvement can compromise colonic blood supply leading to ischemic complications; however, few data exist regarding this problem. We hypothesized that the development of colon involvement in necrotizing pancreatitis (NP) negatively affects morbidity and mortality.

Methods:

Six hundred forty-seven NP patients treated between 2005 and 2017 were retrospectively reviewed to identify patients with colon complications, including ischemia, perforation, fistula, stricture/obstruction, and fulminant Clostridium difficile colitis. Clinical characteristics were analyzed to identify risk factors and effect of colon involvement on morbidity and mortality.

Results:

Colon involvement was seen in 11% (69/647) of NP patients. Ischemia was the most common pathology (n = 29) followed by perforation (n = 18), fistula (n = 12), inflammatory stricture (n = 7), and fulminant C difficile colitis (n = 3). Statistically significant risk factors for developing colon pathology include tobacco use (odds ratio (OR), 2.0; 95% confidence interval (CI), 1.2–3.4, P = 0.009), coronary artery disease (OR, 1.9; 95% CI, 1.1–3.7; P = 0.04), and respiratory failure (OR, 4.7; 95% CI, 1.1–26.3; P = 0.049). When compared with patients without colon involvement, NP patients with colon involvement had significantly increased overall morbidity (86% vs 96%, P = 0.03) and mortality (8% vs 19%, P = 0.002).

Conclusion:

Colon involvement in necrotizing pancreatitis is common; clinical deterioration should prompt its evaluation. Risk factors include tobacco use, coronary artery disease, and respiratory failure. Colon involvement in necrotizing pancreatitis is associated with substantial morbidity and mortality.
Benchmarking Accomplishments of Leaders in American Surgery and Justification for Enhancing Diversity and Inclusion
Authors: Butler Paris D. , Pugh Carla M. , Meer Elana , Lett Elle , Tilahun Estifanos D. , Sanfey Hilary A. , Berry Cherisse , Stain Steven C. , DeMatteo Ronald P. , Vickers Selwyn M. , Britt L. D. , Martin Colin A.
Published: July 2020

Objective:

To comprehensively assess the level of achievement and demographics of national surgical society presidents.

Background:

Data on the accomplishments needed to rise to positions of national surgical leadership is scarce and merit alone does not always yield such opportunities. Recognizing the shortcomings of sex and ethnic diversity within academic surgical leadership, the American College of Surgeon (ACS), American Surgical Association (ASA), Association of Women Surgeons (AWS), and the Society of Black Academic Surgeons (SBAS) partnered to address these challenges by performing a comprehensive assessment of their presidents over the last 16 years.

Methods:

ACS, ASA, AWS, and SBAS presidents’ CVs, at the time of their presidential term, were assessed for demographics and scholastic achievements. Regression analyses controlling for age were performed to determine relative differences across societies.

Results:

A total of 62 of the 64 presidents’ CVs were received and assessed (97% response rate). There was a large discrepancy in the average age in years of ACS (70) and ASA (66) presidents compared to the AWS (51) and SBAS (53) presidents. For the ACS and ASA cohort, 87% were male and 83% were White, collectively. After controlling for age (52), the AWS and SBAS presidents’ scholastic achievements were comparable to the ACS (and ASA) cohort in 9 and 12 of the 15 accessed metrics, respectively.

Conclusion:

The ACS and ASA presidents’ CVs displayed unsurpassed scholastic achievement, and although not equivalent, both the AWS and the SBAS presidents had comparable attainment. These findings further substantiate that women and ethnic minority surgeons are deserving of additional national leadership consideration as organized medicine pursues a more diverse and reflective physician workforce.
The IDEAL Reporting Guidelines
Authors: Bilbro Nicole A. , Hirst Allison , Paez Arsenio , Vasey Baptiste , Pufulete Maria , Sedrakyan Art , McCulloch Peter
Published: July 2020

Objective:

The aim of this study was to define reporting standards for IDEAL format studies.

Background:

The IDEAL Framework and Recommendations establish an integrated pathway for evaluation of new surgical techniques and complex therapeutic technologies. However guidance on implementation has been incomplete, and incorrect use is commonly seen. We describe the consensus development of reporting guidelines for the IDEAL stages, and plans for their dissemination and evaluation.

Methods:

Using the EQUATOR Network recommendations, participants with knowledge of IDEAL were surveyed to determine which IDEAL stages needed reporting guidelines. Draft checklists for stages 1, 2a, 2b, and 4 were subsequently developed by 3 researchers (N.B., A.H., P.M.), and revised through a 2-round Delphi consensus process. A final consensus teleconference resolved outstanding disagreements and clarified wording for checklist items.

Results:

Sixty-one participants completed the initial survey, a clear majority indicating that new reporting guidelines were needed for IDEAL Stage 1 (69.5%), Stage 2a (78%), Stage 2b (74.6%), and Stage 4 (66%). A proposed set of checklists was modified by survey participants in 2 online Delphi rounds (n = 54 and n = 47, respectively), resulting in a penultimate checklist for each stage. Fourteen expert working group members finalized the checklist items and successfully resolved any outstanding areas without agreement on a consensus call.

Conclusions:

Participants familiar with IDEAL called for reporting guidelines for studies in all IDEAL stages except stage 3. The checklists developed have the potential to improve standards of reporting and thereby advance the quality of research on surgery and complex interventions and technologies, but require further evaluation in use.
Bat-borne polyomaviruses in Europe reveal an evolutionary history of intrahost divergence with horseshoe bats distributed across the African and Eurasian continents
Authors: Vidovszky Márton Z. , Tan Zhizhou , Carr Michael J. , Boldogh Sándor , Harrach Balázs , Gonzalez Gabriel
Published: July 2020

Polyomaviruses (PyVs) are small, circular dsDNA viruses carried by diverse vertebrates, including bats. Although previous studies have reported several horseshoe bat PyVs collected in Zambia and China, it is still unclear how PyVs evolved in this group of widely dispersed mammals. Horseshoe bats (genus Rhinolophus) are distributed across the Old World and are natural reservoirs of numerous pathogenic viruses. Herein, non-invasive bat samples from European horseshoe bat species were collected in Hungary for PyV identification and novel PyVs with complete genomes were successfully recovered from two different European horseshoe bat species. Genomic and phylogenetic analysis of the Hungarian horseshoe bat PyVs supported their classification into the genera Alphapolyomavirus and Betapolyomavirus. Notably, despite the significant geographical distances between the corresponding sampling locations, Hungarian PyVs exhibited high genetic relatedness with previously described Zambian and Chinese horseshoe bat PyVs, and phylogenetically clustered with these viruses in each PyV genus. Correlation and virus–host relationship analysis suggested that these PyVs co-diverged with their European, African and Asian horseshoe bat hosts distributed on different continents during their evolutionary history. Additionally, assessment of selective pressures over the major capsid protein (VP1) of horseshoe bat PyVs showed sites under positive selection located in motifs exposed to the exterior of the capsid. In summary, our findings revealed a pattern of stable intrahost divergence of horseshoe bat PyVs with their mammalian hosts on the African and Eurasian continents over evolutionary time.
New perspectives on the calculation of bioaccumulation metrics for active substances in living organisms
Authors: Ratier Aude , Lopes Christelle , Multari Gauthier , Mazerolles Vanessa , Carpentier Patrice , Charles Sandrine
Published: July 2020

Today, only few ready-to-use and convenient decision-making tools are available in ecotoxicology concerning accumulation and effects of chemical substances on organisms, accounting for exposure situations that are known to be complex (routes of exposure, metabolism, mixtures, etc.). This paper presents new perspectives on the generic calculation of bioaccumulation metrics via the innovative web tool MOSAICbioacc(http://mosaic.univ-lyon1.fr/bioacc). MOSAICbioaccprovides all kind of bioaccumulation metrics associated with their uncertainty whatever the species-compound combination. MOSAICbioaccexpects accumulation-depuration data as inputs, even with complex exposure and clearance patterns, to quickly perform their relevant analysis. MOSAICbioaccintends to facilitate the daily work of regulators, or any ecotoxicologist, who will freely benefit from a user-friendly on-line interface that automatically fits toxicokinetic models without needs for users to invest in the technical aspects to get bioaccumulation metrics estimates. MOSAICbioaccalso provides all results in a fully transparent way to ensure reproducibility.
Biodiversity Soup II: A bulk-sample metabarcoding pipeline emphasizing error reduction
Authors: Yang Chunyan , Bohmann Kristine , Wang Xiaoyang , Cai Wang , Wales Nathan , Ding Zhaoli , Gopalakrishnan Shyam , Yu Douglas W.
Published: July 2020

Despite widespread recognition of its great promise to aid decision-making in environmental management, the applied use of metabarcoding requires improvements to reduce the multiple errors that arise during PCR amplification, sequencing, and library generation. We present a co-designed wet-lab and bioinformatic workflow for metabarcoding bulk samples that removes both false-positive (tag jumps, chimeras, erroneous sequences) and false-negative (‘dropout’) errors. However, we find that it is not possible to recover relative-abundance information from amplicon data, due to persistent species-specific biases.

To present and validate our workflow, we created eight mock arthropod soups, all containing the same 248 arthropod morphospecies but differing in absolute and relative DNA concentrations, and we ran them under five different PCR conditions. Our pipeline includes qPCR-optimized PCR annealing temperature and cycle number, twin-tagging, multiple independent PCR replicates per sample, and negative and positive controls. In the bioinformatic portion, we introduceBegum, which is a new version ofDAMe(Zepeda-Mendozaet al. 2016.BMC Res. Notes9:255) that ignores heterogeneity spacers, allows primer mismatches when demultiplexing samples, and is more efficient. LikeDAMe, Begumremoves tag-jumped reads and removes sequence errors by keeping only sequences that appear in more than one PCR above a minimum copy number per PCR. The filtering thresholds are user-configurable.

We report that OTU dropout frequency and taxonomic amplification bias are both reduced by using a PCR annealing temperature and cycle number on the low ends of the ranges currently used for the Leray-FolDegenRev primers. We also report that tag jumps and erroneous sequences can be nearly eliminated withBegumfiltering, at the cost of only a small rise in dropouts. We replicate published findings that uneven size distribution of input biomasses leads to greater dropout frequency and that OTU size is a poor predictor of species input biomass. Finally, we find no evidence for ‘tag-biased’ PCR amplification.

To aid learning, reproducibility, and the design and testing of alternative metabarcoding pipelines, we provide our Illumina and input-species sequence datasets, scripts, a spreadsheet for designing primer tags, and a tutorial.
Bedtk: Finding Interval Overlap with Implicit Interval Tree
Authors: Li Heng , Rong Jiazhen
Published: July 2020

We present bedtk, a new toolkit for manipulating genomic intervals in the BED format. It supports sorting, merging, intersection, subtraction and the calculation of the breadth of coverage. Bedtk employs implicit interval tree, a new data structure for fast interval overlap queries. It is several to tens of times faster than existing tools and tends to use less memory.

Availability

https://github.com/lh3/bedtk

Contact

hli@jimmy.harvard.edu,jiazhen_rong@hms.harvard.edu
Muscle activation patterns are more constrained and regular in treadmill than in overground human locomotion
Authors: Mileti Ilaria , Serra Aurora , Wolf Nerses , Munoz-Martel Victor , Ekizos Antonis , Palermo Eduardo , Arampatzis Adamantios , Santuz Alessandro
Published: July 2020

The use of motorized treadmills as convenient tools for the study of locomotion has been in vogue for many decades. However, despite the widespread presence of these devices in many scientific and clinical environments, a full consensus on their validity to faithfully substitute free overground locomotion is still missing. Specifically, little information is available on whether and how the neural control of movement is affected when humans walk and run on a treadmill as compared to overground. Here, we made use of linear and nonlinear analysis tools to extract information from electromyographic recordings during walking and running overground, and on an instrumented treadmill. We extracted synergistic activation patterns from the muscles of the lower limb via non-negative matrix factorization. We then investigated how the motor modules (or time-invariant muscle weightings) were used in the two locomotion environments. Subsequently, we examined the timing of motor primitives (or time-dependent coefficients of muscle synergies) by calculating their duration, the time of main activation, and their Hurst exponent, a nonlinear metric derived from fractal analysis. We found that motor modules were not influenced by the locomotion environment, while motor primitives resulted overall more regular in treadmill than in overground locomotion, with the main activity of the primitive for propulsion shifted earlier in time. Our results suggest that the spatial and sensory constraints imposed by the treadmill environment forced the central nervous system to adopt a different neural control strategy than that used for free overground locomotion. A data-driven indication that treadmills induce perturbations to the neural control of locomotion.
Extracting neural signals from semi-immobilized animals with deformable non-negative matrix factorization
Authors: Nejatbakhsh Amin , Varol Erdem , Yemini Eviatar , Venkatachalam Vivek , Lin Albert , Samuel Aravinthan D.T. , Paninski Liam
Published: July 2020

Extracting calcium traces from populations of neurons is a critical step in the study of the large-scale neural dynamics that govern behavior. Accurate activity extraction requires the correction of motion and movement-induced deformations as well as demixing of signals that may overlap spatially due to limitations in optical resolution. Traditionally, non-negative matrix factorization (NMF) methods have been successful in demixing and denoising cellular calcium activity in relatively motionless or pre-registered videos. However, standard NMF methods fail in animals undergoing significant non-rigid motion; similarly, standard image registration methods based on template matching can fail when large changes in activity lead to mismatches with the image template. To address these issues simultaneously, we introduce a deformable non-negative matrix factorization (dNMF) framework that jointly optimizes registration with signal demixing. On simulated data and real semi-immobilizedC. elegansmicroscopy videos, dNMF outperforms traditional demixing methods that account for motion and demixing separately. Finally, following the extraction of neural traces from multiple imaging experiments, we develop a quantile regression time-series normalization technique to account for varying neural signal intensity baselines across different animals or different imaging setups. Open source code implementing this pipeline is available athttps://github.com/amin-nejat/dNMF.
Age Influences on the Molecular Presentation of Tumours
Authors: Li Constance H. , Haider Syed , Boutros Paul C.
Published: July 2020

Cancer is often called a disease of aging. There are numerous ways in which cancer epidemiology and behaviour change with the age of the patient. The molecular bases for these relationships remain largely underexplored. To characterize them, we analyzed age-associations in the nuclear and mitochondrial somatic mutational landscape of 20,033 tumours across 35 tumour-types. Age influences both the number of mutations in a tumour and their evolutionary timing. Specific mutational signatures are associated with age, reflecting differences in exogenous and endogenous oncogenic processes such as a greater influence of tobacco use in the tumours of younger patients, but more activity of DNA damage repair signatures in those of older patients. We find that known cancer driver genes are mutated in age-associated frequencies, and these alter the transcriptome and predict for clinical outcomes. These effects are most striking in brain cancers where alterations likeSUFUloss andATRXmutation are age-dependent prognostic biomarkers. Using three cancer datasets, we show that age shapes the somatic mutational landscape of cancer, with clinical implications.
Effects of Different Microplastics on Nematodes in the Soil Environment: Tracking the Extractable Additives using an Ecotoxicological Approach
Authors: Kim Shin Woong , Waldman Walter R. , Rillig Matthias C.
Published: July 2020

With an increasing interest in the effects of microplastic in the soil environment, there is a need to thoroughly evaluate potential adverse effects of these particles as a function of their characteristics (size, shape, and composition). In addition, extractable chemical additives from microplastic have been identified as an important toxicity pathway in the aquatic environment. However, we currently know little about effects of such additives in the soil environment. In this study on nematodes (Caenorhabditis elegans), we adopted an ecotoxicological approach to assess the potential effects of thirteen different microplastics with different characteristics and extractable additives. We found that toxic effects appear to increase in the order of low-density polyethylene (LDPE) film < polypropylene (PP) fragments < high-density polyethylene (HDPE) fragments ≈ polystyrene (PS) fragments < polyethylene terephthalate (PET) fragments ≈ polyacrylicnitrile (PAN) fibers. Acute toxicity was mainly attributed to the extractable additives: when the additives were extracted, the toxic effects of each microplastic disappeared in the acute soil toxicity test. The harmful effects of LDPE film and PAN fibers increased when the microplastics were maintained in soil for a long-term period with frequent wet-dry cycles. We here provide clear evidence that microplastic toxicity in the soil is highly related to particle characteristics and extractable additives. Our results suggest that future experiments consider extractable additives as a key explanatory variable.

Abstract art/Table of contents
A direct interareal feedback-to-feedforward circuit in primate visual cortex
Authors: Siu Caitlin , Balsor Justin , Merlin Sam , Federer Frederick , Angelucci Alessandra
Published: July 2020

The mammalian sensory neocortex consists of hierarchically organized areas reciprocally connected via feedforward (FF) and feedback (FB) circuits. Several theories of hierarchical computation ascribe the bulk of the computational work of the cortex to looped FF-FB circuits between pairs of cortical areas. However, whether such corticocortical loops exist remains unclear. In higher mammals, individual FF-projection neurons send afferents almost exclusively to a single higher-level area. However, it is unclear whether FB-projection neurons show similar area specificity, and whether they influence FF-projection neurons directly or indirectly. Using viral-mediated monosynaptic circuit tracing in macaque primary visual cortex (V1), we show that V1 neurons sending FF projections to area V2 receive monosynaptic FB inputs from V2, but not other V1-projecting areas. We also find monosynaptic FB-to-FB neuron contacts as a second motif of FB connectivity. Our results support the existence of FF-FB loops in primate cortex, and suggest that FB can rapidly and selectively influence the activity of incoming FF signals.
CTCF Mediates Dosage and Sequence-context-dependent Transcriptional Insulation through Formation of Local Chromatin Domains
Authors: Huang Hui , Zhu Quan , Jussila Adam , Han Yuanyuan , Bintu Bogdan , Kern Colin , Conte Mattia , Zhang Yanxiao , Bianco Simona , Chiariello Andrea , Yu Miao , Hu Rong , Juric Ivan , Hu Ming , Nicodemi Mario , Zhuang Xiaowei , Ren Bing
Published: July 2020

Insulators play a critical role in spatiotemporal gene expression in metazoans by separating active and repressive chromatin domains and preventing inappropriate enhancer-promoter contacts. The evolutionarily conserved CCCTC-binding factor (CTCF) is required for insulator function in mammals, but not all of its binding sites act as insulators. Here, we explore the sequence requirements of CTCF-mediated transcriptional insulation with the use of a sensitive insulator reporter assay in mouse embryonic stem cells. We find that insulation potency depends on the number of CTCF binding sites in tandem. Furthermore, CTCF-mediated insulation is dependent on DNA sequences flanking its core binding motifs, and CTCF binding sites at topologically associating domain(TAD) boundaries are more likely to function as insulators than those outside TAD boundaries, independent of binding strength. Using chromosomal conformation capture assays and high-resolution chromatin imaging techniques, we demonstrate that insulators form local chromatin domain boundaries and reduce enhancer-promoter contacts. Taken together, our results provide strong genetic, molecular, and structural evidence connecting chromatin topology to the action of insulators in the mammalian genome.
A Pseudo-Temporal Causality Approach to Identifying miRNA-mRNA Interactions During Biological Processes
Authors: Cifuentes-Bernal Andres M. , Pham Vu VH , Li Xiaomei , Liu Lin , Li Jiuyong , Le Thuc Duy
Published: July 2020

Abstract

Motivation

microRNAs (miRNAs) are important gene regulators and they are involved in many biological processes, including cancer progression. Therefore, correctly identifying miRNA-mRNA interactions is a crucial task. To this end, a huge number of computational methods has been developed, but they mainly use the data at one snapshot and ignore the dynamics of a biological process. The recent development of single cell data and the booming of the exploration of cell trajectories using “pseudo-time” concept have inspired us to develop a pseudo-time based method to infer the miRNA-mRNA relationships characterising a biological process by taking into account the temporal aspect of the process.

Results

We have developed a novel approach, called pseudo-time causality (PTC), to find the causal relationships between miRNAs and mRNAs during a biological process. We have applied the proposed method to both single cell and bulk sequencing datasets for Epithelia to Mesenchymal Transition (EMT), a key process in cancer metastasis. The evaluation results show that our method significantly outperforms existing methods in finding miRNA-mRNA interactions in both single cell and bulk data. The results suggest that utilising the pseudo-temporal information from the data helps reveal the gene regulation in a biological process much better than using the static information.

Availability

R scripts and datasets can be found athttps://github.com/AndresMCB/PTC
Unconventional ER to Endosomal Trafficking by a Retroviral Protein
Authors: Xu Wendy Kaichun , Gou Yongqiang , Lozano Mary M. , Dudley Jaquelin P.
Published: July 2020

Mouse mammary tumor virus (MMTV) encodes a Rem precursor protein that specifies both regulatory and accessory functions. Rem is cleaved at the ER membrane into a functional N-terminal signal peptide (SP) and the C-terminus (Rem-CT). Rem-CT lacks a membrane-spanning domain and a known ER retention signal, yet was not detectably secreted into cell supernatants. Inhibition of intracellular trafficking by the drug Brefeldin A (BFA), which interferes with the ER to Golgi secretory pathway, resulted in dramatically reduced intracellular Rem-CT levels. A Rem mutant lacking glycosylation sites was cleaved into SP and Rem-CT, but was insensitive to BFA, suggesting that unglycosylated Rem-CT does not exit the ER or reach a degradative compartment. BFA reduction of Rem-CT levels was not rescued by proteasome or lysosomal inhibitors. Rem-CT has simple glycans, which are necessary for Rem-CT stability and trafficking, but indicate that Rem-CT does not traffic through the Golgi. Analysis of wild-type Rem-CT and its glycosylation mutant by confocal microscopy revealed that both were primarily localized to the ER lumen. A small fraction of wild-type Rem-CT, but not the unglycosylated mutant, were co-localized with Rab5+ endosomes. Expression of a dominant-negative (DN) form of ADP ribosylation factor 1 (Arf1) (T31N) mimicked the effects of BFA by reducing Rem-CT levels, suggesting that Arf1 prevents Rem-CT localization to a degradative compartment. A DN form of the AAA ATPase, p97/VCP, rescued Rem-CT in the presence of BFA or DN Arf1. Thus, Rem-CT uses an unconventional trafficking scheme, perhaps to thwart innate immunity to MMTV infection.

IMPORTANCE

Mouse mammary tumor virus is a complex retrovirus that encodes a regulatory/accessory protein, Rem. Rem is a precursor protein that is processed at the endoplasmic reticulum (ER) membrane by signal peptidase. The N-terminal SP eludes ER-associated degradation to traffic to the nucleus and serve a human immunodeficiency virus Rev-like function. In contrast, the function of the C-terminal glycosylated cleavage product (Rem-CT) is unknown. Since localization is critical for protein function, we used multiple methods to localize Rem-CT. Surprisingly, Rem-CT, which lacks a transmembrane domain or an ER retention signal, was detected primarily within the ER and required glycosylation for trafficking to endosomes. Blocking of retrograde trafficking through Arf1 reduced Rem-CT levels, but was not restored by lysosomal or proteasomal inhibitors. The unique trafficking of Rem-CT suggests a novel intracellular trafficking pathway, potentially impacting host anti-viral immunity.
A clinical specific BERT developed with huge size of Japanese clinical narrative
Authors: Kawazoe Yoshimasa , Shibata Daisaku , Shinohara Emiko , Aramaki Eiji , Ohe Kazuhiko
Published: July 2020

Generalized language models that pre-trained with a large corpus have achieved great performance on natural language tasks. While many pre-trained transformers for English are published, few models are available for Japanese text, especially in clinical medicine. In this work, we demonstrate a development of a clinical specific BERT model with a huge size of Japanese clinical narrative and evaluated it on the NTCIR-13 MedWeb that has pseudo-Twitter messages about medical concerns with eight labels. Approximately 120 millions of clinical text stored at the University of Tokyo Hospital were used as dataset. The BERT-base was pre-trained with the entire dataset and a vocabulary including 25,000 tokens. The pre-training was almost saturated at about 4 epochs, and the accuracies of Masked LM and Next Sentence Prediction were 0.773 and 0.975, respectively. The developed BERT tends to show higher performances on the MedWeb task than the other nonspecific BERTs, however, no significant differences were found. The advantage of training on domain-specific texts may become apparent in the more complex tasks on actual clinical text, and such corpus for the evaluation is required to be developed.