bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-stage Radialization and Pollicization for Radial Longitudinal Deficiency With Thumb Hypoplasia
Authors: Luangjarmekorn Pobe , Pongernnak Nontich , Yamprasert Nattakul , Kitidumrongsook Pravit
Published: October 2019

Typically, multistage surgeries are usually required for reconstruction of radial longitudinal deficiency with thumb hypoplasia. In this study, we propose single-stage radialization and pollicization for the radial longitudinal deficiency with thumb hypoplasia. The advantages of this technique are to reduce the number of surgical operations, the amount of anesthesia required, and to reduce the cost of multiple follow-ups for patients and family. This technique is noteworthy for the following reasons: (1) use of dorsal vertical midline incision benefit radialization proximal extension for ulnar osteotomy and has less interference with pollicization incision; (2) ulnar shortening osteotomy should be done in case of difficulty in reposition carpus over distal ulnar, overlapping bone, or wrist flexion deformity after complete soft tissue released; (3) recommended fixation technique including predrill and retrograde Kirchner insertion makes for easy osteotomy fixation; (4) exit point of Kirchner wire at the palmar site of the base index metacarpal bone was less interfered with pollicization procedure; and (5) preserved dorso-radial skin bridge between pollicization incision and radialization incision allows for adequate venous draining and prevents postoperative swelling. This technique was carried out on 2 children (4-year-old girl and 2-year-old boy) who presented with type IV radial longitudinal deficiency with unreconstructable hypoplastic thumb. This procedure was successful without any postoperative complications. At 1-year follow-up, the appearance of the wrist was corrected from 90-degree radial angulation to neutral position and from 95-degree to 15-degree radial angulation respectively. For both pollicized thumbs, adequate first web space with proper opposition thumb position was achieved. Thumb tendons started to function at 3 months after surgery. Both patients were able to use their hands to grip light objects with stable carpometacarpal joint and without any pain.
Papillary thyroid microcarcinoma: optimal management versus overtreatment
Authors: Walgama Evan , Sacks Wendy L. , Ho Allen S.
Published: October 2019

Purpose of review

The treatment of small, low-risk papillary thyroid carcinoma has undergone a paradigm shift, with many tumors now initially treated with active surveillance rather than upfront surgery. Further studies on patients enrolled in active surveillance have refined our knowledge of the clinical behavior of papillary thyroid microcarcinomas.

Recent findings

This article summarizes the major conclusions of landmark trials that launched active surveillance as a viable treatment option for selected patients. We discuss patient factors such as age and tumor size, the assessment of candidates for active surveillance, barriers to acceptance of active surveillance, quality of life issues, and economic considerations.

Active Surveillance is a viable first-line treatment option for select papillary microcarcinomas.
Disparities in the Use of Adjuvant External Beam Radiation Therapy in Node-positive Cervical Cancer Patients Following Hysterectomy
Authors: Nasioudis Dimitrios , Musselman Kelsey , Gordhandas Sushmita , Chapman-Davis Eloise , Frey Melissa K. , Caputo Thomas A. , Holcomb Kevin M.
Published: October 2019

Objective:

The objective of this study was to investigate the use of adjuvant external beam radiation therapy (EBRT) among patients with early-stage cervical carcinoma metastatic to regional lymph nodes (LNs).

Materials and Methods:

The National Cancer Database was accessed and patients with early-stage cervical carcinoma diagnosed between 2004 and 2015 were identified. Those with regional LN metastases who had a hysterectomy were selected and administration of adjuvant EBRT was evaluated. Travel distance from the reporting facility was categorized into short (<12.5 miles), intermediate (12.5 to 49.9 miles) and long (>49.9 miles).

Results:

A total of 3436 patients met the inclusion criteria; the rate of EBRT use was 69.7%. Black women were less likely to receive EBRT compared with white (64.2% vs. 70.6%, P=0.037), while patients who had radical hysterectomy were more likely to receive EBRT compared with those who had simple hysterectomy (72.6% vs. 66%, P<0.001). Rates of EBRT administration for patients who traveled short distance was 74.3% compared with 68.9% and 56.9% for those who traveled intermediate and long distance, respectively (P<0.001). On multivariate analysis, patients who traveled long (odds ratio: 0.44, 95% confidence interval [CI]: 0.36, 0.54) or intermediate (OR: 0.73, 95% CI: 0.61, 0.86) distances were less likely to receive EBRT. After controlling for age, race, insurance, presence of comorbidities, stage, histology, and type of hysterectomy, omission of EBRT was associated with worse survival (hazard ratio: 1.53, 95% CI: 1.32, 1.78).

Conclusions:

A large percentage of patients with early-stage cervical cancer and positive LNs did not receive EBRT following hysterectomy. Black women were less likely to receive EBRT than white women. Travel burden may negatively influence appropriate treatment.
Prognostic Nomogram for Hepatitis B Virus–related Hepatocellular Carcinoma With Adjuvant Transarterial Chemoembolization After Radical Resection
Authors: Huang Jian , Liu Fu-Chen , Li Li , Yuan Sheng-Xian , Yang Yuan , Jiang Bei-Ge , Liu Hui , Pan Ze-Ya
Published: October 2019

Objectives:

The objective of this study was to establish a reliable and effective nomogram for predicting prognosis of hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) with postoperative adjuvant transarterial chemoembolization (TACE).

Patients and Methods:

A derivation cohort of 370 HCC patients treated with postoperative TACE in the Eastern Hepatobiliary Surgery Hospital from January 2009 to December 2012 were retrospectively analyzed. Univariate and multivariate analysis were performed by Cox regression and independent prognostic factors for overall survival were determined to construct the nomogram. Concordance index (C-index), calibration curve and decision curve analysis were performed to evaluate the capability of the nomogram and the established nomogram was compared with TNM stage and Barcelona Clinic Liver Cancer (BCLC) stage to identify the superior model. The results were validated in a validation cohort of 123 HCC patients in the same center.

Results:

Multivariate analysis indicated that γ-glutamyl transferase, α-fetoprotein, tumor number, tumor size, satellite lesions, microvascular invasion, and HBV-DNA were independent prognostic factors for overall survival in the derivation cohort, and all these factors were selected into the nomogram. The C-index was 0.755 for survival prediction of the nomogram, which was significantly higher than the TNM stage (0.636, P<0.001) and BCLC stage (0.594, P<0.001). A fair uniformity and a superior net benefit with wide range threshold probabilities were showed in the calibration curves and decision curve analysis. In the validation cohort, the C-index of the nomogram (0.785) also had a higher predictive accuracy than TNM stage (0.744, P=0.019) and BCLC stage (0.616, P<0.001).

Conclusions:

The nomogram with accurate and reasonable performance was proposed for predicting survival of HBV-related HCC with postoperative adjuvant TACE.
Comparison of the effects of two different teaching methods in blood pressure measurement training: a randomized controlled study
Authors: Terzi Banu , Topbaş Eylem , Bingöl Gülay , Mavi Aydoğdu Saadet Gonca
Published: October 2019

Objective:

To compare the effects of a high-fidelity simulator and conventional teaching model used during blood pressure measurement training on students’ self-confidence, self-efficacy and anxiety levels.

Methods:

A randomized controlled trial design was used. The study was conducted on 59 first-year nursing students of a university in Amasya, Turkey. ‘Self-Confidence Scale,’ ‘general Self-Efficacy Scale’ and ‘Beck Anxiety Scale’ were used to collect the data. A high-fidelity simulator used in blood pressure measurement training was applied to the experimental group, while the conventional method in which the students practice on their peers was applied to the control group. Chi-square, Mann–Whitney U test and the Wilcoxon signed-rank test were used to determine the difference between the two groups’ average.

Results:

No statistically significant difference was found between students’ pre-test and post-test total scores of self-confidence, general self-efficacy and anxiety scales with the high-fidelity simulator and the conventional model (P > 0.05). A significant increase was noted in inner self-confidence and self-efficacy scores of the group working on the high-fidelity simulator (P < 0.05).

Conclusions:

The high-fidelity simulator was effective on the students’ increased levels of self-confidence and self-efficacy, whereas it was not effective on their anxiety levels. However, this study can also be conducted on a larger sample group using a variety of training methods.
Prospective evaluation of 68Ga-DOTANOC positron emission tomography/computed tomography and 131I-meta-iodobenzylguanidine single-photon emission computed tomography/computed tomography in extra-adrenal paragangliomas, including uncommon primary sites and to define their diagnostic roles in current scenario
Authors: Arora Saurabh , Kumar Rakesh , Passah Averilicia , Tripathi Madhavi , Agarwala Sandeep , Khadgawat Rajesh , Bal Chandrasekhar
Published: October 2019

Aim

To evaluate 68Ga-DOTANOC positron emission tomography/computed tomography (PET/CT) and 131I-meta-iodobenzylguanidine single-photon emission computed tomography/computed tomography (131I-MIBG SPECT/CT) in patients with paragangliomas, including uncommon primaries.

Methods

Ninety patients were prospectively enrolled, and both scans were done within 2 weeks of each other. Lesions were grouped as Head/neck, abdominal, uncommon primary paraganglioma, and metastatic lesions. In most histopathology was used as reference standard.

Results

PET/CT had sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 97%, 94%, 99%,88%,97% respectively on patient wise analysis (90) and 98%, 94%, 99%, 85% and 97% respectively on lesion wise analysis (149). Comparison with MIBG SPECT/CT: Significant difference in sensitivities noted (PET/CT-98%, I-131 MIBG -39%) (P < 0.001), however, no significant difference in specificities (94% and 100%, respectively). Group-wise analysis: Head/Neck: Significant difference noted between PET/CT (sensitivity 100%) and I-131 MIBG SPECT/CT (sensitivity 22%) (P = 0.001). Abdominal: No significant difference noted in sensitivities and specificities of PET/CT and I-131 MIBG SPECT/CT. Uncommon paraganglioma: PET/CT detected 10 of 11, while I-131 MIBG detected only 2 of 11 uncommon paraganglioma. Metastatic sites: Significant difference noted between PET/CT (sensitivity 97%) and I-131 MIBG SPECT/CT (sensitivity 33%) (P < 0.0001).

Conclusion

The study demonstrates high diagnostic accuracy of 68Ga-DOTANOC PET/CT and superiority over 131I MIBG SPECT/CT for evaluation of extra-adrenal paraganglioma. The current diagnostic role of I-131 MIBG seems limited to abdominal paragangliomas and for theranostic purpose.
Mothers' Reasons for Early Breastfeeding Cessation
Authors: Morrison April H. , Gentry Retha , Anderson Joanna
Published: October 2019

Purpose:

The purpose of this review is to assess maternal explanations for early breastfeeding cessation in economically developed countries.

Study Design and Methods:

The electromic databases EBSCO, CINAHL, Child Development & Adolescent Studies, PsycInfo, Health Source: Nursing/Academic Edition, Nursing and Allied Health; ProQuest databases: Family Health Database, Health and Medical Collection, Nursing and Allied Health, Psychology Database, and Public Health Databases were searched using the terms breastfeeding, cessation, stop, discontinuation, early weaning, quit∗, early termination, and six months. Inclusion criteria included infants born at least 37 weeks gestation, single birth, and infant birthweight > 2,500 g.

Results:

Initial literature search yielded 117 studies; 10 studies met inclusion criteria. The two most common reasons for early breastfeeding cessation were perceived inadequate milk supply and maternal breast or nipple pain.

Conclusion:

Research on maternal reasons for early breastfeeding cessation is limited. Reasons for early breastfeeding cessation are varied; however, the most common themes were perceived inadequate supply and breast or nipple pain. Nurses should tailor assessment of each breastfeeding mother-baby couplet and associated interventions based on these findings.
Perioperative Management in Patients With Cleft Lip and Palate
Authors: Preidl Raimund H.M. , Kesting Marco , Rau Andrea
Published: October 2019

In cleft care, perioperative treatment strategies like ear nose and throat (ENT) diagnostics as well as postoperative antibiotics, feeding, and duration of inpatient stay are nonstandardized procedures varying between different centers. Likewise, intraoperative choice of suture materials and time of suture removal are performed inconsistently. Therefore, we wanted to collect information on protocols focusing on these topics to summarize and subsume currently approved treatment strategies of centers around the world. We ask members of international cleft centers for their respective treatment strategies and performed descriptive statistics.

Absorbable suture material is used for reconstruction of the outer lip skin in 20 of 70 centers. Removal of skin sutures is conducted after 7.0 ± 1.5 days. Suturing of the orbicularis oris muscle, the enoral and nasal mucosa, as well as the palatal musculature is predominantly performed with absorbable suture materials. Intraoperative antibiotic prophylaxis is applied in 82.9% of the participating centers. In contrast, 31.9% of the departments do not apply any antibiotic postoperatively. Postoperative feeding is performed in 27 centers via a nasogastric tube for 4.6 ± 2.3 days on average. Mean length of postoperative inpatient stay is 4.1 ± 2.6 days in children after cleft lip surgery and 4.5 ± 2.7 days after cleft palate surgery. ENT consultation before surgery is routinely conducted in 52.8% of the centers and 82.9% of ENT colleagues investigate middle ear pathologies in the same operation in which cleft repair is performed.

Closure of the lip skin is predominantly performed with nonabsorbable suture material followed by a suture removal after 1 week. Intraoperative antibiotic prophylaxis as well as inpatient hospital stay of 4 to 5 days in combination with oral feeding and a preoperative consultation and intraoperative cooperation with the ENT department seems to be well-proven concepts in cleft lip palate patient care. However, this analysis illustrated the variations and differing approaches in perioperative care emphasizing the need to verify perioperative management concepts in cleft surgery—preferably in the context of multicenter studies.
Locus of Control and Cognition in Older Adults With Type 1 Diabetes
Authors: Eng Chloe W. , Gilsanz Paola , Lacy Mary E. , Beeri Michal Schnaider , Whitmer Rachel A.
Published: October 2019

Objective:

Life expectancy for individuals with type 1 diabetes mellitus (T1DM) has increased recently; however, it is unknown how diabetes care attitudes affect late-life brain health.

Research Design and Methods:

The Study of Longevity in Diabetes (SOLID) consists of 734 older adults with T1DM, reporting diabetes locus of control (dLOC), age of diabetes diagnosis and other demographics, history of hypoglycemic episodes, and depressive symptoms. Global and domain-specific (language, executive function, episodic memory, simple attention) cognitive functioning was assessed at in-person interviews. Cross-sectional associations between dLOC and cognition were estimated using covariate-adjusted linear regression models in pooled and sex-stratified models.

Results:

In pooled analyses, a 1-point increase in dLOC (more internal) was positively associated with global cognition [β=0.05, 95% confidence interval (CI): 0.02, 0.07], language (β=0.04, 95% CI: 0.01, 0.07), and executive function (β=0.04, 95% CI: 0.01, 0.07), but not episodic memory or simple attention. However, in sex-stratified analyses, this effect was seen only in males and not females.

Conclusions:

In elderly individuals with T1DM, we found associations between dLOC and cognition overall and in men but not women. Underlying sex differences should be considered in future research or interventions on psychosocial characteristics for cognition.
Structure, Process, and Quality Indicators for Pressure Injury Prevention and Care in Austrian Hospitals
Authors: Hoedl Manuela , Eglseer Doris , Lohrmann Christa
Published: October 2019

The purpose of this quality improvement point-prevalence project conducted in 2017 was to describe the structure, process, and outcome indicators for pressure injury (PI) prevention and care in 37 Austrian hospitals with 208 wards and 2955 patients, with an average age of 66 years. Structural indicators such as PI guideline availability were measured on hospital and ward levels. On the process level, patients were assessed to determine whether PI interventions such as mobilization or use of moisturizer/barrier cream were implemented. On the outcome level, data on the presence of hospital-acquired PIs based on skin inspection were collected. These data were collected using the Austrian version of the National Prevalence Measurement of Care Problems, a standardized survey. Structural level results showed PI protocols or guidelines were available in 75.7% of the participating institutions. Staff education such as refresher courses was seldom available on the ward level (46.6%). Process-level results indicated the most commonly applied intervention in both patients at risk of or had a PI was the use of skin-protectant moisture barrier creams (63.1% and 85.2%, respectively). Patients with PIs also frequently received interventions focusing on the heels (72.9%) and mobilization (69.2%). With regard to the outcome level, the overall and hospital-acquired PI prevalence rates were 3.6% and 1.3%, respectively. We recommend focusing on staff, patient and family education including the prevention and treatment of hydration and nutritional deficits, an uncommonly used intervention in Austria based on these data, to improve the quality of PI prevention and care in the hospital setting.
Patient Preferences to Undergo Low-Value CT Coronary Angiography in the Emergency Department
Authors: Winkels Jessica L. , Smith Chelsea Morrow , Iyengar Rahul , Meka Arjun P. , Porath Jonathan D. , Meurer William J.
Published: October 2019

Background

Low-value diagnostic testing adds billions of dollars to the cost of health care in the US annually. Addressing patient preference for these tests is one possible strategy to limit overuse. In previous work, we showed that patient preference for testing can be influenced by test benefit, risk, and financial measures. Our objective was to examine the effect of these variables in another clinical scenario involving chest pain.

Methods

In this cross-sectional survey of patients at the University of Michigan Emergency Department (ED), participants were given a hypothetical scenario involving an ED visit for chest pain, along with information regarding potential benefit (detecting a life-threatening condition; 0.1 or 1%) and risk (developing cancer; 0.1 or 1%) of CTCA, as well as an incentive of $0 or $100 to forego testing. Values for risk, benefit, and financial incentive varied across participants. Our primary outcome was patient preference to undergo testing. We also obtained demographic and numeracy information. Then, we used logistic regression to estimate odds ratios, adjusting for multiple potential confounders. Our sample size was designed to find at least 300 events (test acceptance) to allow for up to 30 covariates in fully adjusted models. We had 85-90% power to detect a 10% absolute difference in testing rate across groups, assuming a 95% significance level.

Results

913 patients were surveyed. A $100 financial incentive (adjusted OR [AOR] 0.57; 95% Confidence Interval [CI] 0.42-0.78) and increased test risk (AOR 0.61; 95% CI 0.44-0.84) both significantly decreased test acceptance in fully adjusted models, whereas increased test benefit significantly increased test acceptance (AOR 2.45; 95% CI 1.79-3.36).

Conclusions

Offering a financial incentive deterred patients from accepting testing despite varying levels of risk and benefit. In the context of previous work, we provide preliminary evidence supporting that financial interventions may impact patient preference more than test risk and benefit.
Computational Modeling of Ovarian Cancer Reveals Optimal Strategies for Therapy and Screening
Authors: Gu Shengqing , Lheureux Stephanie , Sayad Azin , Cybulska Paulina , Hogen Liat Ben-David , Vyarvelska Iryna , Tu Dongsheng , Parulekar Wendy , Nankivell Matthew , Kehoe Sean , Chi Dennis , Levine Douglas A. , Bernardini Marcus Q. , Rosen Barry , Oza Amit , Neel Benjamin G.
Published: October 2019

High-grade serous tubo-ovarian carcinoma (HGSC) is a major cause of cancer-related death. Whether treatment order—primary debulking surgery followed by adjuvant chemotherapy (PDS) or neo-adjuvant chemotherapy with interval surgery (NACT)—affects outcome is controversial. We developed a mathematical framework that holds for hierarchical or stochastic models of tumor initiation and reproduces HGSC clinical course. After estimating parameter values, we infer that most patients harbor chemo-resistant HGSC cells at diagnosis, and that if complete debulking (<1 mm residual tumor) can be achieved, PDS is superior to NACT due to better depletion of resistant cells. We further predict that earlier diagnosis of primary HGSC, followed by complete debulking, could improve survival, but its benefit in relapsed patients is likely to be limited. Our predictions are supported by primary clinical data from multiple cohorts. Our results have clear implications for these key issues in HGSC management.

Significance Statement

The optimal order and timing of surgery and chemotherapy, and the potential benefits of earlier diagnosis of HGSC, remain controversial. We developed a mathematical framework of tumor dynamics to address such issues, populated the model with primary clinical data and reliably recapitulated clinical observations. Our model prospectively predicts that: (1) PDS is superior to NACT when complete debulking is feasible; (2) timely adjuvant chemotherapy is critical for the outcome of PDS with <1mm, but not >1mm, residual tumors; (3) earlier detection of relapse is unlikely to be beneficial with current therapies; (4) earlier detection of primary HGSC, followed by complete debulking, could have substantial benefit. Our model provides insights into the evolutionary dynamics of HGSC, argues for new clinical trials to optimize HGSC therapy, and is potentially applicable to other tumor types.
Yersinia canariaesp. nov., isolated from a human yersiniosis case
Authors: Nguyen Scott V. , Greig David R. , Hurley Daniel , Cao Yu , McCabe Evonne , Mitchell Molly , Jenkins Claire , Fanning Séamus
Published: October 2019

A Gram-negative rod from theYersiniagenus was isolated from a clinical case of yersiniosis in the United Kingdom. Long read sequencing data from an Oxford Nanopore Technology (ONT) MinION in conjunction with Illumina HiSeq reads were used to generate a finished quality genome of this strain. Overall Genome Related Index (OGRI) of the strain was used to determine that it was a novel species withinYersinia, despite biochemical similarities toYersinia enterocolitica. The 16S ribosomal RNA gene accessions areMN434982-MN434987and the accession number for the complete and closed chromosome isCP043727.The type strain is CFS3336T(=NCTC 14382T/ =LMGAccession under process).
Enhancer prediction in the human genome by probabilistic modelling of the chromatin feature patterns
Authors: Osmala Maria , Lähdesmäki Harri
Published: October 2019

Background

The binding sites of transcription factors (TFs) and the localisation of histone modifications in the human genome can be quantified by the chromatin immunoprecipitation assay coupled with next-generation sequencing (ChIP-seq). The resulting chromatin feature data has been successfully adopted for genome-wide enhancer identification by several unsupervised and supervised machine learning methods. However, the current methods predict different numbers and different sets of enhancers for the same cell type and do not utilise the pattern of the ChIP-seq coverage profiles efficiently.

Results

In this work, we propose a PRobabilistic Enhancer PRedictIoN Tool (PREPRINT) that assumes characteristic coverage patterns of chromatin features at enhancers and employs a statistical model to account for their variability. PREPRINT defines probabilistic distance measures to quantify the similarity of the genomic query regions and the characteristic coverage patterns. The probabilistic scores of the enhancer and non-enhancer samples are utilised to train a kernel-based classifier. The performance of the method is demonstrated on ENCODE data for two cell lines. The predicted enhancers are computationally validated based on the transcriptional regulatory protein binding sites and compared to the predictions obtained by state-of-the-art methods.

Conclusion

PREPRINT performs favorably to the state-of-the-art methods, especially when requiring the methods to predict a larger set of enhancers. PREPRINT generalises successfully to data from cell type not utilised for training, and often the PREPRINT performs better than the previous methods. The PREPRINT enhancers are less sensitive to the choice of prediction threshold. PREPRINT identifies biologically validated enhancers not predicted by the competing methods. The enhancers predicted by PREPRINT can aid the genome interpretation in functional genomics and clinical studies.

Availability

https://github.com/MariaOsmala/preprint

Contact

maria.osmala@aalto.fi
Phenomenal: An automatic open source library for 3D shoot architecture reconstruction and analysis for image-based plant phenotyping
Authors: Artzet Simon , Chen Tsu-Wei , Chopard Jérôme , Brichet Nicolas , Mielewczik Michael , Cohen-Boulakia Sarah , Cabrera-Bosquet Llorenç , Tardieu François , Fournier Christian , Pradal Christophe
Published: October 2019

In the era of high-throughput visual plant phenotyping, it is crucial to design fully automated and flexible workflows able to derive quantitative traits from plant images. Over the last years, several software supports the extraction of architectural features of shoot systems. Yet currently no end-to-end systems are able to extract both 3D shoot topology and geometry of plants automatically from images on large datasets and a large range of species. In particular, these software essentially deal with dicotyledons, whose architecture is comparatively easier to analyze than monocotyledons. To tackle these challenges, we designed the Phenomenal software featured with: (i) a completely automatic workflow system including data import, reconstruction of 3D plant architecture for a range of species and quantitative measurements on the reconstructed plants; (ii) an open source library for the development and comparison of new algorithms to perform 3D shoot reconstruction and (iii) an integration framework to couple workflow outputs with existing models towards model-assisted phenotyping. Phenomenal analyzes a large variety of data sets and species from images of high-throughput phenotyping platform experiments to published data obtained in different conditions and provided in a different format. Phenomenal has been validated both on manual measurements and synthetic data simulated by 3D models. It has been also tested on other published datasets to reproduce a published semi-automatic reconstruction workflow in an automatic way. Phenomenal is available as an open-source software on a public repository.
How do we segment text? Two-stage chunking operation in reading
Authors: Yang Jinbiao , Cai Qing , Tian Xing
Published: October 2019

Chunking in language comprehension is a process that segments continuous linguistic input into smaller chunks that are in reader’s mental lexicon. Effective chunking during reading facilitates disambiguation and enhances efficiency for comprehension. However, the mechanisms of chunking remain elusive, especially in reading given that information arrives simultaneously yet the written systems may not have explicit cues for labeling boundaries such as Chinese. What are the mechanisms of chunking operation that mediates the reading of the text that normally contains hierarchical information? We investigated this question by manipulating the lexical status of the chunks at distinct levels of grain-size in four-character Chinese strings, including the two-character local chunk and four-character global chunk. Participants were asked to make lexical decision on these strings in a behavioral experiment, followed by a passive reading task when their electroencephalography (EEG) were recorded. The behavioral results showed that the lexical decision time of lexicalized two-character local chunks was influenced by the lexical status of four-character global chunk, but not vice versa, which indicated that the processing of global chunks possessed priority over the local chunks. The EEG results revealed that familiar lexical chunks were detected simultaneously at both levels and further processed in a different temporal order -- the onset of lexical access for the global chunks was earlier than that of local chunks. These consistent behavioral and EEG results suggest that chunking in reading occurs at multiple levels via a two-stage operation -- simultaneous detection and global-first recognition.

Significance Statement

The learners of a new language often read word by word. But why can proficient readers read multiple words at a time? The current study investigates how we efficiently segment a complicate text into smaller pieces and how we process these pieces. Participants read Chinese strings with different structures while their key-press responses and brain EEG signals were recorded. We found that texts were quickly (about 100 ms from their occurrences) segmented to varied sizes of pieces, and larger pieces were then processed earlier than small pieces. Our results suggest that readers can use existing knowledge to efficiently segment and process written information.
Genome profiles of lymphovascular breast cancer cells reveal multiple clonally differentiated outcomes with multi-regional LCM and G&T-seq
Authors: Zhu ZhongYi , Wang Weiwei , Lin Feng , Jordan Tracy , Li Guibo , Silverman Sveta , Qiu Si , Joy Anil Abraham , Chen Chao , Hockley Deanna , Zhang Xi , Zhou Qing , Postovit Lynne-Marie , Zhang Xiuqing , Hou Yong , Mackey John R. , Li Bo , Wong Gane Ka-Shu
Published: October 2019

Lymphovascular invasion (LVI) is a critical step in the metastatic process but has received relatively little attention due to the technical challenges associated with their isolation. In this study, we used laser capture microdissection (LCM) to isolate 97 cancer cell clusters from pathological frozen sections within lymphatic vessels, primary tumor tissue, and axillary lymph nodes of a triple negative breast cancer (TNBC) patient. Simultaneous genome and transcriptome amplification and sequencing (G&T-seq) performed on these clusters permitted a comprehensive depiction of the genomic and transcriptional profiles of cancer cells associated with LVI. Combination phylogeny analysis pointed to three evolutionarily distinct pathways of tumor clone development and metastasis in this patient, each of which was associated with a unique mRNA signature, and correlated to disparate overall survival outcomes. Moreover, hub gene evaluation found extensive down regulation of ribosomal protein mRNA to be a potential marker of poor prognosis in breast cancer patients.
Functional analysis of phospholipase Dδ family in tobacco pollen tubes
Authors: Pejchar Přemysl , Sekereš Juraj , Novotný Ondřej , Žárský Viktor , Potocký Martin
Published: October 2019

Phosphatidic acid (PA), important signalling and metabolic phospholipid, is predominantly localized in the subapical plasma membrane (PM) of growing pollen tubes. PA can be produced from structural phospholipids by phospholipase D (PLD) but the isoforms responsible for production of plasma membrane PA were not identified yet and their functional roles remain unknown. Following genome-wide bioinformatic analysis of PLD family in tobacco, we focused on the pollen-overrepresented PLDδ class. Combining live-cell imaging, gene overexpression or knock-down, lipid-binding and structural bioinformatics, we characterized 5 NtPLDδ isoforms. Distinct PLDδ isoforms preferentially localize to the cytoplasm or subapical PM. Using fluorescence recovery after photobleaching, domain deletion and swapping analyses we show that membrane-bound PLDδs are tightly bound to PM, primarily via the central catalytic domain. Knock-down, overexpression andin vivoPA level analyses revealed isofom PLDδ3 as the most important member of the PLDδ subfamily active in pollen tubes. PA promotes binding of PLDδ3 to the PM, thus creating a positive feedback loop, where PA accumulation leads to the formation of massive PM invaginations. Tightly controlled production of PA generated by PLDδ3 at the PM is important for maintaining the balance between various membrane trafficking processes, that are crucial for plant cell tip growth.
Mitochondrial Dysfunction Induces Epigenetic Dysregulation by H3K27 Hyperacetylation to Perturb Active Enhancers in Parkinson’s Disease Models
Authors: Huang Minhong , Lou Dan , Charli Adhithiya , Kong Dehui , Jin Huajun , Anantharam Vellareddy , Kanthasamy Arthi , Wang Zhibin , Kanthasamy Anumantha G.
Published: October 2019

Genetic mutations explain only 10-15% of cases of Parkinson’s disease (PD), while an overriding environmental component has been implicated in the etiopathogenesis of PD. But regardless of where the underlying triggers for the onset of familial and sporadic PD fall on the gene-environment axis, mitochondrial dysfunction emerges as a common mediator of dopaminergic neuronal degeneration. Herein, we employ a multidisciplinary approach to convincingly demonstrate that neurotoxicant exposure- and genetic mutation-driven mitochondrial dysfunction share a common mechanism of epigenetic dysregulation. Under both scenarios, lysine 27 acetylation of likely variant H3.2 (H3.2K27ac) increased in dopaminergic neuronal models of PD, thereby opening that region to active enhancer activity via H3K27 hyperacetylation. These vulnerable epigenomic loci represent potential transcription factor motifs for PD pathogenesis. We further confirmed the mitochondrial dysfunction induced H3K27ac during neurodegeneration inex vivomodels of PD. Our results reveal an exciting axis of ‘exposure/mutation-mitochondrial dysfunction-metabolism-H3K27ac-transcriptome’ for PD pathogenesis. Collectively, the novel mechanistic insights presented here interlinks mitochondrial dysfunction to epigenetic transcriptional regulation in dopaminergic degeneration as well as offer potential new epigenetic intervention strategies for PD.
Semiparametric Partial Common Principal Component Analysis for Covariance Matrices
Authors: Wang Bingkai , Luo Xi , Zhao Yi , Caffo Brian
Published: October 2019

Summary

We consider the problem of jointly modeling multiple covariance matrices by partial common principal component analysis (PCPCA), which assumes a proportion of eigenvectors to be shared across covariance matrices and the rest to be individual-specific. This paper proposes consistent estimators of the shared eigenvectors in PCPCA as the number of matrices or the number of samples to estimate each matrix goes to infinity. We prove such asymptotic results without making any assumptions on the ranks of eigenvalues that are associated with the shared eigenvectors. When the number of samples goes to infinity, our results do not require the data to be Gaussian distributed. Furthermore, this paper introduces a sequential testing procedure to identify the number of shared eigenvectors in PCPCA. In simulation studies, our method shows higher accuracy in estimating the shared eigenvectors than competing methods. Applied to a motor-task functional magnetic resonance imaging data set, our estimator identifies meaningful brain networks that are consistent with current scientific understandings of motor networks during a motor paradigm.
The unfolded protein response regulates pathogenic development ofUstilago maydisby Rok1-dependent inhibition of mating-type signaling
Authors: Schmitz Lara , Schwier Melina Ayaka , Heimel Kai
Published: October 2019

Fungal pathogens require the unfolded protein response (UPR) to maintain protein homeostasis of the endoplasmic reticulum (ER) during pathogenic development. In the corn smut fungusUstilago maydis, pathogenic development is controlled by theaandbmating-type loci. The UPR is specifically activated after plant penetration and required for efficient secretion of effectors and suppression of the plant defense response. The interaction between the UPR regulator Cib1 and the central developmental regulator Clp1 modulates the pathogenic program and triggers fungal colonization of the host plant. By contrast, when activated before plant penetration, the UPR interferes with fungal virulence by reducing expression ofbEandbW, the central regulators of pathogenic development encoded by thebmating-type locus. Here we show that this inhibitory effect results from UPR-mediated suppression of the pheromone response pathway upstream of theb-regulatory network. UPR activity prompts dephosphorylation of the pheromone-responsive MAPK Kpp2, reducing activity of the pheromone response factor Prf1 that regulates expression ofbEandbW. Deletion of the dual specificity phosphataserok1fully suppressed UPR-dependent inhibition of Kpp2 phosphorylation, formation of infectious filaments and fungal virulence. Rok1 determines activity of mating-type signaling pathways and thus the degree of fungal virulence. We propose that UPR-dependent regulation of Rok1 aligns ER physiology with fungal aggressiveness and effector gene expression during biotrophic growth ofU. maydisin the host plant.

Importance

The unfolded protein response (UPR) is crucial for ER homeostasis and disease development in fungal pathogens. In the plant pathogenic fungusUstilago maydis, the UPR supports fungal proliferationin plantaand effector secretion for plant defense suppression. In this study, we uncovered that UPR activity, which is normally restricted to the biotrophic stagein planta, inhibits mating and the formation of infectious filaments by Rok1-dependent dephosphorylation of the pheromone responsive MAPK Kpp2. This observation is relevant for understanding how the fungal virulence program is regulated by cellular physiology. UPR-mediated control of mating-type signaling pathways predicts that effector gene expression and the virulence potential are controlled by ER stress levels.
Call for participation: Collaborative benchmarking of functional-structural root architecture models. The case of root water uptake
Authors: Schnepf Andrea , Black Christopher K. , Couvreur Valentin , Delory Benjamin M. , Doussan Claude , Koch Axelle , Koch Timo , Javaux Mathieu , Landl Magdalena , Leitner Daniel , Lobet Guillaume , Mai Trung Hieu , Meunier Félicien , Petrich Lukas , Postma Johannes A. , Priesack Eckart , Schmidt Volker , Vanderborght Jan , Vereecken Harry , Weber Matthias
Published: October 2019

Three-dimensional models of root growth, architecture and function are becoming important tools that aid the design of agricultural management schemes and the selection of beneficial root traits. However, while benchmarking is common in many disciplines that use numerical models such as natural and engineering sciences, functional-structural root architecture models have never been systematically compared. The following reasons might induce disagreement between the simulation results of different models: different representation of root growth, sink term of root water and solute uptake and representation of the rhizosphere. Presently, the extent of discrepancies is unknown, and a framework for quantitatively comparing functional-structural root architecture models is required. We propose, in a first step, to define benchmarking scenarios that test individual components of complex models: root architecture, water flow in soil and water flow in roots. While the latter two will focus mainly on comparing numerical aspects, the root architectural models have to be compared at a conceptual level as they generally differ in process representation. Therefore defining common inputs that allow recreating reference root systems in all models will be a key challenge. In a second step, benchmarking scenarios for the coupled problems are defined. We expect that the results of step 1 will enable us to better interpret differences found in step 2. This benchmarking will result in a better understanding of the different models and contribute towards improving them. Improved models will allow us to simulate various scenarios with greater confidence and avoid bugs, numerical errors or conceptual misunderstandings. This work will set a standard for future model development.
DeCoDe: degenerate codon design for complete protein-coding DNA libraries
Authors: Shimko Tyler C. , Fordyce Polly M. , Orenstein Yaron
Published: October 2019

Motivation

High-throughput protein screening is a critical technique for dissecting and designing protein function. Libraries for these assays can be created through a number of means, including targeted or random mutagenesis of a template protein sequence or direct DNA synthesis. However, mutagenic library construction methods often yield vastly more non-functional than functional variants and, despite advances in large-scale DNA synthesis, individual synthesis of each desired DNA template is often prohibitively ex-pensive. Consequently, many protein screening libraries rely on the use of degenerate codons (DCs), mixtures of DNA bases incorporated at specific positions during DNA synthesis, to generate highly diverse protein variant pools from only a few low-cost synthesis reactions. However, selecting DCs for sets of sequences that covary at multiple positions dramatically increases the difficulty of designing a DC library and leads to the creation of many undesired variants that can quickly outstrip screening capacity.

Results

We introduce a novel algorithm for total DC library optimization, DeCoDe, based on integer linear programming. DeCoDe significantly outperforms state-of-the-art DC optimization algorithms and scales well to more than a hundred proteins sharing complex patterns of covariation (e.g.the lab-derived avGFP lineage). Moreover, DeCoDe is, to our knowledge, the first DC design algorithm with the capability to encode mixed-length protein libraries. We anticipate DeCoDe to be broadly useful for a variety of library generation problems, ranging from protein engineering attempts that leverage mutual information to the reconstruction of ancestral protein states.

Availability

github.com/OrensteinLab/DeCoDe

Contact

yaronore@bgu.ac.il
Path integration in large-scale space and with novel geometries: Comparing Vector Addition and Encoding-Error Models
Authors: Harootonian S. K. , Wilson R. C. , Hejtmánek L. , Ziskin E. M. , Ekstrom A. D.
Published: October 2019

Path integration is thought to rely on vestibular and proprioceptive cues yet most studies in humans involve primarily visual input, providing limited insight into their contributions. We developed a paradigm involving walking in an omnidirectional treadmill in which participants were guided on two legs of a triangle and then found their back way to origin. In Experiment 1, we tested a range of different triangle types while keeping distance relatively constant to determine the influence of spatial geometry. Participants overshot the angle they needed to turn and undershot the distance they needed to walk, with no consistent effect of triangle type. In Experiment 2, we manipulated distance while keeping angle relatively constant to determine how path integration operated over both shorter and longer distances. Participants underestimated the distance they needed to walk to the origin, with error increasing as a function of the walked distance. To attempt to account for our findings, we developed computational models involving vector addition, the second of which included terms for the influence of past trials on the current one. We compared against a previously developed model of human path integration, the Encoding Error model. We found that the vector addition models captured the tendency of participants to under-encode guided legs of the triangles and an influence of past trials on current trials. Together, our findings expand our understanding of body-based contributions to human path integration, further suggesting the value of vector addition models in understanding these important components of human navigation.

Author Summary

How do we remember where we have been? One important mechanism for doing so is called path integration, which refers to the ability to track one’s position in space with only self-motion cues. By tracking the direction and distance we have walked, we can create a mental arrow from the current location to the origin, termed the homing vector. Previous studies have shown that the homing vector is subject to systematic distortions depending on previously experienced paths, yet what influences these patterns of errors, particularly in humans, remains uncertain. In this study, we compare two models of path integration based on participants walking two legs of a triangle without vision and then completing the third leg based on their estimate of the homing vector. We found no effect of triangle shape on systematic errors, while path length scaled the systematic errors logarithmically, similar to Weber-Fechner law. While we show that both models captured participant’s behavior, a model based on vector addition best captured the patterns of error in the homing vector. Our study therefore has important implications for how humans track their location, suggesting that vector-based models provide a reasonable and simple explanation for how we do so.
Fine human genetic map based on UK10K data set
Authors: Hao Ziqian , Du Pengyuan , Pan Yi-Hsuan , Li Haipeng
Published: October 2019

Recombination is a major force that shapes genetic diversity. Determination of recombination rate is important and can theoretically be improved by increasing the sample size. However, it is challenging to estimate recombination rates when the sample size is extraordinarily large because of computational burden. In this study, we used a refined artificial intelligence approach to estimate the recombination rate of the human genome using the UK10K human genomic dataset with 7,562 genomic sequences and its three subsets with 200, 400 and 2,000 genomic sequences under the Out-of-Africa demography model. We not only obtained an accurate human genetic map, but also found that the fluctuation of estimated recombination rate is reduced along the human genome when the sample size is increased. UK10K recombination activity is less concentrated than its subsets. Our results demonstrate how the sample size affects the estimated recombination rate, and analyses of a larger number of genomes result in a more precise estimation of recombination rate.