bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensitive alignment using paralogous sequence variants improves long-read mapping and variant calling in segmental duplications
Authors: Prodanov Timofey , Bansal Vikas 
Published: September 2020

Abstract
The ability to characterize repetitive regions of the human genome is limited by the read lengths of short-read sequencing technologies. Although long-read sequencing technologies such as Pacific Biosciences (PacBio) and Oxford Nanopore Technologies can potentially overcome this limitation, long segmental duplications with high sequence identity pose challenges for long-read mapping. We describe a probabilistic method, DuploMap, designed to improve the accuracy of long-read mapping in segmental duplications. It analyzes reads mapped to segmental duplications using existing long-read aligners and leverages paralogous sequence variants (PSVs)—sequence differences between paralogous sequences—to distinguish between multiple alignment locations. On simulated datasets, DuploMap increased the percentage of correctly mapped reads with high confidence for multiple long-read aligners including Minimap2 (74.3–90.6%) and BLASR (82.9–90.7%) while maintaining high precision. Across multiple whole-genome long-read datasets, DuploMap aligned an additional 8–21% of the reads in segmental duplications with high confidence relative to Minimap2. Using DuploMap-aligned PacBio circular consensus sequencing reads, an additional 8.9 Mb of DNA sequence was mappable, variant calling achieved a higher F1 score and 14 713 additional variants supported by linked-read data were identified. Finally, we demonstrate that a significant fraction of PSVs in segmental duplications overlaps with variants and adversely impacts short-read variant calling.
Senescence-activated enhancer landscape orchestrates the senescence-associated secretory phenotype in murine fibroblasts
Authors: Guan Yiting , Zhang Chao , Lyu Guoliang , Huang Xiaoke , Zhang Xuebin , Zhuang Tenghan , Jia Lumeng , Zhang Lijun , Zhang Chen , Li Cheng , Tao Wei 
Published: September 2020

Abstract
The three-dimensional configuration of the chromatin architecture is known to be crucial for alterations in the transcriptional network; however, the underlying mechanisms of epigenetic control of senescence-related gene expression by modulating the chromatin architecture remain unknown. Here, we demonstrate frequent chromosomal compartment switching during mouse embryonic fibroblasts (MEFs) replicative senescence as characterized by senescence-inactivated (SIAEs) and -activated enhancers (SAEs) in topologically associated domains (TADs). Mechanistically, SAEs are closely correlated with senescence-associated secretory phenotype (SASP) genes, which are a key transcriptional feature of an aging microenvironment that contributes to tumor progression, aging acceleration, and immunoinflammatory responses. Moreover, SAEs can positively regulate robust changes in SASP expression. The transcription factor CCAAT/enhancer binding protein α (C/EBPα) is capable of enhancing SAE activity, which accelerates the emergence of SAEs flanking SASPs and the secretion of downstream factors, contributing to the progression of senescence. Our results provide novel insight into the TAD-related control of SASP gene expression by revealing hierarchical roles of the chromatin architecture, transcription factors, and enhancer activity in the regulation of cellular senescence.
Direct measurement of protein–protein interactions by FLIM-FRET at UV laser-induced DNA damage sites in living cells
Authors: Kaufmann Tanja , Herbert Sébastien , Hackl Benjamin , Besold Johanna Maria , Schramek Christopher , Gotzmann Josef , Elsayad Kareem , Slade Dea 
Published: September 2020

AbstractProtein–protein interactions are essential to ensure timely and precise recruitment of chromatin remodellers and repair factors to DNA damage sites. Conventional analyses of protein–protein interactions at a population level may mask the complexity of interaction dynamics, highlighting the need for a method that enables quantification of DNA damage-dependent interactions at a single-cell level. To this end, we integrated a pulsed UV laser on a confocal fluorescence lifetime imaging (FLIM) microscope to induce localized DNA damage. To quantify protein–protein interactions in live cells, we measured Förster resonance energy transfer (FRET) between mEGFP- and mCherry-tagged proteins, based on the fluorescence lifetime reduction of the mEGFP donor protein. The UV-FLIM-FRET system offers a unique combination of real-time and single-cell quantification of DNA damage-dependent interactions, and can distinguish between direct protein–protein interactions, as opposed to those mediated by chromatin proximity. Using the UV-FLIM-FRET system, we show the dynamic changes in the interaction between poly(ADP-ribose) polymerase 1, amplified in liver cancer 1, X-ray repair cross-complementing protein 1 and tripartite motif containing 33 after DNA damage. This new set-up complements the toolset for studying DNA damage response by providing single-cell quantitative and dynamic information about protein–protein interactions at DNA damage sites.
DockCoV2: a drug database against SARS-CoV-2
Authors: Chen Ting-Fu , Chang Yu-Chuan , Hsiao Yi , Lee Ko-Han , Hsiao Yu-Chun , Lin Yu-Hsiang , Tu Yi-Chin Ethan , Huang Hsuan-Cheng , Chen Chien-Yu , Juan Hsueh-Fen 
Published: September 2020

AbstractThe current state of the COVID-19 pandemic is a global health crisis. To fight the novel coronavirus, one of the best-known ways is to block enzymes essential for virus replication. Currently, we know that the SARS-CoV-2 virus encodes about 29 proteins such as spike protein, 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), Papain-like protease (PLpro), and nucleocapsid (N) protein. SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) for viral entry and transmembrane serine protease family member II (TMPRSS2) for spike protein priming. Thus in order to speed up the discovery of potential drugs, we develop DockCoV2, a drug database for SARS-CoV-2. DockCoV2 focuses on predicting the binding affinity of FDA-approved and Taiwan National Health Insurance (NHI) drugs with the seven proteins mentioned above. This database contains a total of 3,109 drugs. DockCoV2 is easy to use and search against, is well cross-linked to external databases, and provides the state-of-the-art prediction results in one site. Users can download their drug-protein docking data of interest and examine additional drug-related information on DockCoV2. Furthermore, DockCoV2 provides experimental information to help users understand which drugs have already been reported to be effective against MERS or SARS-CoV. DockCoV2 is available at https://covirus.cc/drugs/.
Adding Physical Impairment to Risk Stratification Improved Outcome Prediction in Low Back Pain
Authors: Beneciuk Jason M , George Steven Z 
Published: September 2020

Abstract

Objective
Identifying subgroups of low back pain (LBP) has the potential to improve prediction of clinical outcomes. Risk stratification is one such strategy that identifies similar characteristics indicative of a common clinical outcome trajectory. The purpose of this study was to determine if an empirically derived subgrouping approach based on physical impairment measures improves information provided from the STarT Back Tool (SBT).

Methods
At baseline in this secondary analysis of a cohort study, patients (N = 144) receiving physical therapy for LBP completed the SBT and tests (active lumbar flexion, extension, lateral bending, and passive straight-leg raise) from a validated physical impairment index. Clinical outcomes were assessed at 4 weeks and included the Numerical Pain Rating Scale and Oswestry Disability Index. Exploratory hierarchical agglomerative cluster analysis identified empirically derived subgroups based on physical impairment measures. Independent samples t testing and chi-square analysis were used to assess baseline subgroup differences in demographic and clinical measures. Spearman rho correlation coefficient was used to assess baseline SBT risk and impairment subgroup relationships, and a 3-way mixed-model ANOVA was used to assessed SBT risk and impairment subgroup relationships with clinical outcomes at 4 weeks.

Results
Two physical impairment-based subgroups emerged from cluster analysis: (1) low-risk impairment (n = 119, 81.5%), characterized by greater lumbar mobility; and (2) high-risk impairment (n = 25, 17.1%), characterized by less lumbar mobility. A weak, positive relationship was observed between baseline SBT risk and impairment subgroups (rs = .170). An impairment-by-SBT risk-by-time interaction effect was observed for Oswestry Disability Index scores but not for Numerical Pain Rating Scale scores at 4 weeks.

Conclusions
Physical impairment subgroups were not redundant with SBT risk categories and could improve prediction of 4-week LBP disability outcomes. Physical impairment subgroups did not improve the prediction of 4-week pain intensity scores.

Impact
Subgroups based on physical impairment and psychosocial risk could lead to better prediction of LBP disability outcomes and eventually allow for treatment options tailored to physical and psychosocial risk.
Dr Fossile’s Crocodile: Science and the ‘Oriental Chronotope’ in Eighteenth-Century Literature
Authors: Risling Matthew 
Published: September 2020

Abstract
This article explores eighteenth-century questions surrounding the spatiotemporal nature of the field we now call ‘science’. Today’s commonplace notion of ‘modern Western science’ assumes conceptual binaries that do not map onto eighteenth-century discourses. The article focuses on two works by the so-called Scriblerians—Three Hours after Marriage (1717), and Memoirs of Martinus Scriblerus (1714, pub. 1741)—which satirize the much-maligned Dr John Woodward and, ostensibly, the philosophical mode he represented. Though these texts are satirical, the article does not posit a clash of cultures. Instead, it examines a set of tropes, shared by numerous authors at various purposes, which inflected science with the narratological space-time of the ancient Orient. This ‘Oriental chronotope’ (in Bakhtinian terms) speaks to the complex space that science occupied in emerging narratives of Western modernity. The Eastern artefacts featured in these works, and their shared themes of dubious reproduction, establish an unlikely affinity with Thomas Sprat’s History of the Royal Society (1667), which offers the new sciences as a dialectic between the ancient and modern worlds.
Differences in clinical characteristics of IgG4-related disease across age groups: a prospective study of 737 patients
Authors: Lu Hui , Teng Fei , Zhang Panpan , Fei Yunyun , Peng Linyi , Zhou Jiaxin , Wang Mu , Liu Xiaowei , Zhu Liang , Wang Liwen , Luo Xuan , Liu Zheng , Li Jieqiong , Zhao Yan , Zhang Wen , Zeng Xiaofeng 
Published: September 2020

Abstract

Objective
The aim of this study was to compare the clinical characteristics of IgG4-related disease (IgG4-RD) among different age groups.

Methods
We conducted a prospective study of 737 patients who were newly diagnosed with IgG4-RD and compared detailed demographic features, organ involvements, laboratory tests, treatments and outcomes across age groups. The patients were divided into five groups according to their age at diagnosis: ≤39, 40–49, 50–59, 60–69 and ≥70 years. The clinical characteristics of paediatric patients were also described.

Results
Sex ratio, disease duration, allergy history and clinical symptoms were significantly different across age groups. Besides, the proportions of superficial organ involvement (lacrimal gland and sinus) decreased with age, while the proportions of internal organ involvement (pancreas, biliary tract, retroperitoneal tissue, lung and prostate) increased with age, which was more prominent in male patients. Mikulicz’s disease was the most common manifestation (70%) in paediatric IgG4-RD patients. Multiple Cox analysis identified that age ≤56 years at diagnosis was an independent risk factor of relapse.

Conclusion
We revealed the impact of age on clinical characteristics of IgG4-RD, which indicated that different management might be required among different age groups.
Smoke Chemistry, In Vitro Cytotoxicity, and Genotoxicity Demonstrates Enhanced Toxicity of Cigarillos Compared With Cigarettes
Authors: Crosby Lynn , Yucesoy Berran , Leggett Carmine , Tu Zheng , Belinsky Steven A , McDonald Jake , Leng Shuguang , Wu Guodong , Irshad Hammad , Valerio Luis G , Rosenfeldt Hans 
Published: September 2020

Abstract
There has been limited toxicity testing of cigarillos, including comparison to cigarettes. This study compared the smoke chemistry and the cytotoxic and genotoxic potential of 10 conventional cigarettes and 10 cigarillos based on the greatest market share. Whole smoke and total particulate matter (TPM) were generated using the Canadian Intense and International Organization for Standardization puffing protocols. Tobacco-specific nitrosamines, carbonyls, and polycyclic aromatic hydrocarbons were measured using gas chromatography-mass spectrometry. TPM smoke extracts were used for the in vitro assays. Cytotoxicity was assessed in human bronchial epithelial continuously cultured cell line cells using the neutral red uptake assay. Genotoxic potential was assessed using the micronucleus (human lung adenocarcinoma continuously cultured cell line cells), Ames, and thymidine kinase assays. TPM from all cigarillos tested was more cytotoxic than cigarettes. Micronucleus formation was significantly greater for cigarillos compared with cigarettes at the highest dose of TPM, with or without rat liver S9 fraction. In the Ames test +S9, both tobacco products exhibited significant dose-dependent increases in mutation frequency, indicating metabolic activation is required for genotoxicity. In the thymidine kinase assay +S9, cigarillos showed a significantly enhanced mutation frequency although both tobacco products were positive. The levels of all measured polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines, and carbonyls (except acrolein) were significantly greater in cigarillos than cigarettes. The Canadian Intense puffing protocol demonstrated increased smoke constituent levels compared with International Organization for Standardization. Even though the gas vapor phase was not tested, the results of this study showed that under the tested conditions the investigated cigarillos showed greater toxicity than comparator cigarettes. This study found that there is significantly greater toxicity in the tested U.S. marketed cigarillos than cigarettes for tobacco constituent levels, cytotoxicity, and genotoxicity. These findings are important for understanding the human health toxicity from the use of cigarillos relative to cigarettes and for building upon knowledge regarding harm from cigarillos to inform risk mitigation strategies.
Development of a Telemedicine Neurological Examination for Spine Surgery
Authors: Goyal Dhruv K.C. , Divi Srikanth N. , Schroeder Gregory D. , Pfeifer Ryan , Canseco Jose A. , Bowles Daniel R. , Nicholson Kristen J. , Patel Parthik D. , Reyes Ariana A. , Radcliff Kristen E. , Kurd Mark F. , Woods Barrett I. , Kaye Ian David , Rihn Jeffrey A. , Anderson David Greg , Hilibrand Alan S. , Kepler Christopher K. , Harrop James S. , Vaccaro Alexander R. 
Published: September 2020

Study Design:
This was a prospective cohort study.

Objective:
The objective of this study was to design and test a novel spine neurological examination adapted for telemedicine.

Summary of Background Data:
Telemedicine is a rapidly evolving technology associated with numerous potential benefits for health care, especially in the modern era of value-based care. To date, no studies have assessed whether.

Methods:
Twenty-one healthy controls and 20 patients with cervical or lumbar spinal disease (D) were prospectively enrolled. Each patient underwent a telemedicine neurological examination as well as a traditional in-person neurological examination administered by a fellowship trained spine surgeon and a physiatrist. Both the telemedicine and in-person tests consisted of motor, sensory, and special test components. Scores were compared via univariate analysis and secondary qualitative outcomes, including responses from a satisfaction survey, were obtained upon completion of the trial.

Results:
Of the 20 patients in the D group, 9 patients had cervical disease and 11 patients had lumbar disease. Comparing healthy control with the D group, there were no significant differences with respect to all motor scores, most sensory scores, and all special tests. There was a high rate of satisfaction among the cohort with 92.7% of participants feeling “very satisfied” with the overall experience.

Conclusions:
This study presents the development of a viable neurological spine examination adapted for telemedicine. The findings in this study suggest that patients have comparable motor, sensory, and special test scores with telemedicine as with a traditional in-person examination administered by an experienced clinician, as well as reporting a high rate of satisfaction among participants. To our knowledge, this is the first telemedicine neurological examination for spine surgery. Further studies are warranted to validate these findings.
Combined Anterior-Posterior Versus Posterior-only Spinal Fusion in Treating Dystrophic Neurofibromatosis Scoliosis With Modern Instrumentation
Authors: Jia Fei , Wang Guodong , Sun Jianmin , Liu Xiaoguang 
Published: September 2020

Study Design:
This is a systematic review and meta-analysis study.

Objectives:
To compare the efficacy, long-term stability, and safety of combined anterior-posterior spinal fusion (APSF) with posterior-only spinal fusion (PSF) in treating dystrophic neurofibromatosis scoliosis with the use of modern instrumentation.

Summary of Background Data:
When the Harrington or Luque technique was used, APSF had relatively reliable results and had been recommended by many authors. But with the development of instrumentation and techniques, many surgeons performed PSF with satisfactory results. No systematic review and meta-analysis have been conducted to compare the outcomes of the 2 approaches.

Materials and Methods:
Relevant studies on anterior-posterior or posterior fusion of dystrophic neurofibromatosis scoliosis were retrieved from the PubMed, Embase, Cochrane, Springer Link, and Google Scholar databases. Then studies were manually selected for inclusion based on predefined criteria. Data extraction and quality assessment were conducted, and a systematic review and meta-analysis were performed.

Results:
Sixteen eligible studies were included. The angles of scoliosis curves and kyphosis curves were significantly and similarly corrected after surgery in both APSF and PSF group, respectively. At the last follow-up, the loss of correction was significant in the coronal plane but not in the sagittal plane with a similar progression of scoliosis in 2 groups. The overall complication rate was slightly higher in the APSF group, but the difference was not statistically significant. Meanwhile, there was no visible difference in the incidence of pseudarthrosis and instrumentation failures between the 2 groups.

Conclusions:
APSF and PSF by means of the third-generation spinal instrumentation system have similar efficacy, long-term stability, and safety for treating dystrophic scoliosis secondary to type-1 neurofibromatosis.

Level of Evidence:
Level III—systematic review and meta-analysis study.
New Classification Algorithm Guiding Surgical Decision-making for Posterior Longitudinal Ligament Ossification of the Thoracic Spine
Authors: Liu Xiao , Xu Nanfang , Yang Xiaosong , Liu Xiaoguang , Yu Miao , Liu Zhongjun 
Published: September 2020

Study Design:
This is a single-center, retrospective, cohort study.

Objective:
The objective of this study was to propose a surgical classification algorithm guiding the choice of surgical approaches for ossification of the posterior longitudinal ligament (OPLL) in the thoracic spine based on the characteristics of each patient’s specific pathology.

Summary of Background Data:
Surgical decision-making in this OPLL patient population requires balancing a more definitive decompression of the thoracic spinal cord through direct decompression against a higher risk of significant complications.

Materials and Methods:
Patients with a primary diagnosis of thoracic OPLL who received surgical decompression in a tertiary spine center between May 2009 and June 2015 were included. Surgical planning was guided by our classification algorithm according to the location and the extent of OPLL in each patient. Patient demographics, neurological function using the 11-point Japanese Orthopaedic Association scale, length of procedure, estimated blood loss, the occurrence of major complications, etc., were extracted from the database of electronic medical record system. The Kruskal-Wallis test and Fisher exact test were used when data were not normally distributed.

Results:
A total of 115 patients (33 men and 82 women) were included in this study, among whom 108 had a follow-up of at least 12 months (average: 51.7±22.2 mo, range: 12–100 mo). On the basis of our classification algorithm, 11 patients were type I, 26 were type II, 60 were type III, 11 were type IV, and the choice of surgical decompression techniques used in each patient followed that recommended by the algorithm in all cases. On average, the Japanese Orthopaedic Association score improved from 5.0±1.8 preoperatively to 8.7±1.7 postoperatively, with a Hirabayashi improvement rate of 63.6%.

Conclusion:
A new surgical classification algorithm guiding the choice of approach for decompression of OPLL in the thoracic spine was validated in a series of 108 patients through an analysis of their clinical outcomes and surgical complications.

Level of Evidence:
Level III.
Feasibility Study of Electromagnetic Muscle Stimulation and Cryolipolysis for Abdominal Contouring
Authors: Kilmer Suzanne L. , Cox Sue Ellen , Zelickson Brian D. , Bachelor Eric P. , Gamio Sylvia , Ostrowski Rafael , Pham Linda D. , Stevens W. Grant 
Published: September 2020

BACKGROUND
In addition to reducing subcutaneous fat for body contouring, some patients are interested in toning the underlying muscle layer.

OBJECTIVE
This feasibility study evaluated the safety and efficacy of electromagnetic muscle stimulation (EMMS) alone, cryolipolysis alone, and cryolipolysis with EMMS for noninvasive contouring of abdomen.

METHODS
Abdomens of 50 subjects were treated in a study with 3 cohorts: EMMS alone, Cryolipolysis alone, and Cryolipolysis + EMMS in combination. Electromagnetic muscle stimulation treatments were delivered in 4 sessions over 2 weeks. Cryolipolysis treatments were delivered in one session. Combination treatments consisted of one cryolipolysis and 4 EMMS visits. Efficacy was assessed by independent physician Global Aesthetic Improvement Scale (GAIS), circumferential measurement, Subject GAIS (SGAIS), and Body Satisfaction Questionnaire (BSQ).

RESULTS
Safety was demonstrated for all study cohorts with no device- or procedure-related adverse events. Independent photo review showed greatest mean GAIS score for the Cryolipolysis + EMMS cohort followed by Cryolipolysis only, then EMMS only cohort. BSQ showed greatest average score increase for Cryolipolysis + EMMS cohort followed by Cryolipolysis only cohort, then EMMS only cohort. Mean circumferential reduction measurements were greatest for Cryolipolysis + EMMS cohort followed by Cryolipolysis only, and then EMMS only cohort. The mean SGAIS improvement score was equal for the Cryolipolysis only and Cryolipolysis + EMMS cohorts, followed by the EMMS only cohort.

CONCLUSION
A multimodal approach using cryolipolysis and EMMS was safe and demonstrated enhanced body contouring efficacy for this feasibility study.