bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Trial Evaluating Esophageal Anastomotic Reinforcement with a Biologic, Degradable, Extracellular Matrix after Total Gastrectomy and Esophagectomy
Authors: Vos Elvira L , Nakauchi Masaya , Capanu Marinela , Park Bernard J , Coit Daniel G , Molena Daniela , Yoon Samuel S , Jones David R , Strong Vivian E 
Published: April 2022

BACKGROUND:
A biologic, degradable extracellular matrix (ECM) has been shown to support esophageal tissue remodeling, which could reduce the risk of anastomotic leak following total gastrectomy and esophagectomy. We evaluated the safety and efficacy of reinforcing the anastomosis with ECM in reducing anastomotic leak as compared to a matched cohort.

STUDY DESIGN:
In this single-center, nonrandomized phase II trial, gastric or esophageal adenocarcinoma patients undergoing total gastrectomy or esophagectomy were recruited from November 2013 through December 2018. ECM was surgically wrapped circumferentially around the anastomosis. Anastomotic leak was assessed clinically and by contrast study and defined as clinically significant if requiring invasive treatment (grade 3 or higher). Anastomotic stenosis, other adverse events, symptoms, and dysphagia score were collected by standardized forms at regular follow-up visits at approximately postoperative days (POD) 21 and 90. Patients receiving ECM were compared to a cohort matched for surgery type and age.

RESULTS:
ECM placement was not feasible in 9 of 75 patients (12%), resulting in 66 patients receiving ECM. Total gastrectomy was performed in 50 patients (76%) and esophagectomy in 16 (24%). Clinically significant anastomotic leak was diagnosed in 6 of 66 patients (9.1%) (3/50 [6.0%] after gastrectomy, 3/16 [18.8%] after esophagectomy); this rate did not differ from that in the matched cohort (p = 0.57). Stenosis requiring invasive treatment occurred in 8 patients (12.5%), and 10 patients (15.6%) reported not being able to eat a normal diet at POD 90. No adverse events related to ECM were reported.

CONCLUSIONS:
Esophageal anastomotic reinforcement after total gastrectomy or esophagectomy with a biologic, degradable ECM was mostly feasible and safe, but was not associated with a statistically significant decrease in anastomotic leak.
Rectal Cancer in Patients with Hereditary Nonpolyposis Colorectal Cancer Compared with Sporadic Cases: Response to Neoadjuvant Chemoradiation and Local Recurrence
Authors: Madbouly Khaled M , Emile Sameh Hany , Issa Yasmine Amr 
Published: April 2022

BACKGROUND:
This study aimed to assess the effect of neoadjuvant chemoradiation (nCXRT) on tumor regression and oncologic outcome of middle and low rectal cancer in patients of hereditary nonpolyposis colorectal cancer (HNPCC) compared to sporadic cases.

STUDY DESIGN:
This was a retrospective cohort study that compared the outcomes of patients with HNPCC presenting with middle or low rectal cancer indicated for nCXRT vs patients with sporadic rectal cancer. All patients received long-course nCXRT followed by total mesorectal excision. Primary outcome was pathologic tumor regression grade (TRG) assessed after resection. Secondary outcomes included disease-free survival and overall survival.

RESULTS:
Fifty-eight patients with HNPCC (24 female) were included in the study matched with 58 patients with sporadic rectal cancer (out of 166 using propensity score matching). Patients with HNPCC and sporadic rectal cancer were matched regarding tumor pathology TNM stage and lymphovascular invasion. In the HNPCC group, 36 patients (62%) had tumor regression (TRG3 = 6 (10.3%); TRG2 = 12 (20.6%); TRG1 = 18 (31%)) compared to 52 patients (92%) who had tumor regression in the control group (TRG4 = 9; TRG3 = 15; TRG2 = 18; TRG1 = 10) (p < 0.0007). After a median follow-up of 48 months, survival analysis revealed higher local recurrence and lower overall survival in patients with HNPCC compared to patients with sporadic rectal cancer.

CONCLUSIONS
Rectal cancer in patients with HNPCC showed poorer response to nCXRT and was followed by higher local recurrence and lower overall survival than patients with sporadic rectal cancer. Tumor regression was detected in <65% of patients with HNPCC compared to >90% of patients with sporadic rectal cancer, and none of patients with HNPCC had a complete response.
A Method to improve the Reliability of Saliency Scores applied to Graph Neural Network Models in Patient Populations
Authors: Ochoa Juan G. Diaz , Mustafa Faizan E 
Published: April 2022

AbstractGraph Neural Networks (GNN), a novel method to recognize features in heterogeneous information structures, have been recently used to model patients with similar diagnoses, extract relevant features and in this way predict for instance medical procedures and therapies. For applications in a medical field is relevant to leverage the interpretability of GNNs and evaluate which model inputs are involved in the computation of the model outputs, which is a useful information to analyze correlations between diagnoses and therapies from large datasets. We present in this work a method to sample the saliency scores of GNNs models computed with three different methods, gradient, integrated gradients, and DeepLIFT. The final sample of scores informs the customers if they are reliable if and only if all of them are convergent. This method will be relevant to inform customers which is the degree of confidence and interpretability of the computed predictions obtained with GNNs models.
Evaluation of Outdoor swimming courses as an intervention to refresh and revitalise NHS workers
Authors: Pett Pippa , Massey Heather , Denton Hannah , Burlingham Amy , Harper Mark 
Published: April 2022

AbstractBackgroundFrontline healthcare staff working in the National Health Service (NHS) have been, and continue to be, under a significant level of work related stress as a result of the COVID-19 pandemic. Long hours and greater clinical need have impacted negatively on work-life balance. The results of our preliminary studies indicate that outdoor swimming may be an effective treatment for anxiety and depression. We therefore hypothesised that the activity could improve symptoms of work-related burnout and stress in NHS workers. The primary objective of this study was to gather feedback from NHS staff participating in supervised swimming sessions that took place in an outdoor pool in London and the sea in Cornwall on the value and effectiveness of this initiative as they perceived it.MethodsFollowing ethical approval (University of Portsmouth Science and Health research ethics committee SHFEC 2021-066), participants who had signed up to outdoor swimming courses provided by NHS Improvement in Cornwall and London were asked to give their consent to participate in an online survey. They were asked to complete them at three time-points: the week prior to, upon completion and six weeks after completion of the outdoor swimming course. As well as being asked for qualitative feedback, participants completed the Short Warwick-Edinburgh Mental Wellbeing Scale and the Copenhagen Burnout Inventory.Results85 (63.9%) of the 133 Participants who signed up to outdoor swimming courses completed the first survey, 62 (49.6%) the second and 43 (35.5%) the third. 41 (33.8%) completed all three surveys. Overall, there was a 14.8% increase in wellbeing scores when comparing the scores before and after the courses which was statistically significant (p<0.0001, d= 1.02). Compared to scores before the course, the scores at its conclusion were reduced by 25%, 18% and 18% in personal, work-related and client-related burnout respectively. These burnout scores were significantly different for personal (P<0.0001) and work-related burnout (P=0.0018). Qualitative feedback was overwhelmingly positive with the effects being broadly divided into those relating to mood and physical health, the social aspects of the group activity, feelings of achievement and self-care and mindfulness.ConclusionThis research suggests that the outdoor swimming activity, as a workplace intervention, can be an effective way of promoting staff wellbeing and reducing personal and work-related burnout. Further, formal trials of this intervention are justified.
Identifying type 1 and 2 diabetes in population level data: assessing the accuracy of published approaches
Authors: Thomas Nicholas J , McGovern Andrew , Young Katherine G , Sharp Seth A , Weedon Michael N , Hattersley Andrew T , Dennis John , Jones Angus G 
Published: April 2022

AbstractAimsPopulation datasets are increasingly used to study type 1 or 2 diabetes, and inform clinical practice. However, correctly classifying diabetes type, when insulin treated, in population datasets is challenging. Many different approaches have been proposed, ranging from simple age or BMI cut offs, to complex algorithms, and the optimal approach is unclear. We aimed to compare the performance of approaches for classifying insulin treated diabetes for research studies, evaluated against two independent biological definitions of diabetes type.MethodWe compared accuracy of thirteen reported approaches for classifying insulin treated diabetes into type 1 and type 2 diabetes in two population cohorts with diabetes: UK Biobank (UKBB) n=26,399 and DARE n=1,296. Overall accuracy and predictive values for classifying type 1 and 2 diabetes were assessed using: 1) a type 1 diabetes genetic risk score and genetic stratification method (UKBB); 2) C-peptide measured at >3 years diabetes duration (DARE).ResultsAccuracy of approaches ranged from 71%-88% in UKBB and 68%-88% in DARE. All approaches were improved by combining with requirement for early insulin treatment (<1 year from diagnosis). When classifying all participants, combining early insulin requirement with a type 1 diabetes probability model incorporating continuous clinical features (diagnosis age and BMI only) consistently achieved high accuracy, (UKBB 87%, DARE 85%). Self-reported diabetes type alone had high accuracy (UKBB 87%, DARE 88%) but was available in just 15% of UKBB participants. For identifying type 1 diabetes with minimal misclassification, using models with high thresholds or young age at diagnosis (<20 years) had the highest performance. An online tool developed from all UKBB findings allows the optimum approach of those tested to be selected based on variable availability and the research aim.ConclusionSelf-reported diagnosis and models combining continuous features with early insulin requirement are the most accurate methods of classifying insulin treated diabetes in research datasets without measured classification biomarkers.
Declining National Codeine Distribution in United States Hospitals and Pharmacies from 2011 to 2019
Authors: Kennalley Amy L. , Boureghda Youcef A. , Ganesh Jay G. , Watkins Adam M. , McCall Kenneth L. , Piper Brian J. 
Published: April 2022

AbstractBackgroundPast research has identified pronounced regional disparities in use of different opioids but less is known for codeine. The primary objective of this study was to analyze the trends of distribution of prescriptions containing codeine in the United States (US) from 2010 to 2019. In addition, this study aimed to identify regional disparities in prescribed milligrams of codeine per person in 2019 and identify any unusual states.MethodsThe distribution of codeine via pharmacies, hospitals, and practitioners in kilograms was obtained from the Drug Enforcement Administration’s Automated Reports and Consolidated Ordering System (ARCOS) from 2010 to 2019. In addition, the number of prescriptions of codeine per 1,000 Medicaid enrollees was obtained from the State Drug Utilization Database.ResultsThe total grams of codeine decreased (−25.0%) through all distributors from 2010 to 2019. The largest increase in total grams of codeine distributed between two consecutive years (2014 to 2015) was +28.9%. For a given distributor type, the largest decrease from 2010 to 2019 was hospitals (−89.6%). In 2019, the total mg of codeine per person distributed in Texas (11.46) was significantly higher relative to the national average (3.06, 1.88 SD). Codeine prescriptions to Medicaid patients peeked in the third quarter of 2016.ConclusionThe peak of prescription codeine in 2011 was consistent with the overall peak in prescription opioids, with a subsequent decrease over the decade. This could be explained by relatively recent recommendations regarding the therapeutic use of codeine and how other antitussive agents may be of better use. The precipitous rise of codeine in Texas that we observed has been recognized in prior studies. These state-level disparities warrant further attention by opioid stewardship committees.
Knowledge-graph-based cell-cell communication inference for spatially resolved transcriptomic data with SpaTalk
Authors: Shao Xin , Li Chengyu , Yang Haihong , Lu Xiaoyan , Liao Jie , Qian Jingyang , Wang Kai , Cheng Junyun , Yang Penghui , Chen Huajun , Xu Xiao , Fan Xiaohui 
Published: April 2022

AbstractSpatially resolved transcriptomics (ST) provides genetic information in space toward elucidation of the spatial architecture in intact organs and the spatially resolved cell-cell communications mediating tissue homeostasis, development, and disease. To facilitate inference of spatially resolved cell-cell communications from ST data, we here present SpaTalk, which relies on a graph network and knowledge graph to model and score the ligand-receptor-target signaling network between spatially proximal cells, decomposed from ST data through a non-negative linear model and spatial mapping between single-cell RNA-sequencing and ST data. The performance of SpaTalk benchmarked on public single-cell ST datasets was superior to that of existing cell-cell communication inference methods. SpaTalk was then applied to STARmap, Slide-seq, and 10X Visium data, revealing the in-depth communicative mechanisms underlying normal and disease tissues with spatial structure. SpaTalk can uncover spatially resolved cell-cell communications for single-cell and spot-based ST data universally, providing new insights into spatial inter-cellular dynamics.
Representational integration and differentiation in the human hippocampus following goal-directed navigation
Authors: Fernandez Corey , Jiang Jiefeng , Wang Shao-Fang , Choi Hannah L. , Wagner Anthony D. 
Published: April 2022

AbstractAs we learn, dynamic memory processes build structured knowledge across our experiences. Such knowledge enables the formation of internal models of the world that we use to plan, make decisions, and act. Recent theorizing posits that mnemonic mechanisms of differentiation and integration – which at one level may seem to be at odds – both contribute to the emergence of structured knowledge. We tested this possibility using fMRI as human participants learned to navigate within local and global virtual environments over the course of three days. Pattern similarity analyses on entorhinal cortex, hippocampus, and ventromedial prefrontal cortex patterns revealed evidence that differentiation and integration work concurrently to build local and global environmental representations, and that variability in integration relates to differences in navigation efficiency. These results offer new insights into the neural machinery and the underlying mechanisms that translate experiences into structured knowledge that allows us to navigate to achieve goals.
General Features of Transmembrane Beta Barrels From a Large Database
Authors: Montezano Daniel , Bernstein Rebecca , Copeland Matthew M. , Slusky Joanna S. G. 
Published: April 2022

AbstractLarge datasets contribute new insights to subjects formerly investigated by exemplars. We used co-evolution data to create a large, high-quality database of transmembrane β-barrels (TMBB). By applying simple feature detection on generated evolutionary contact maps, our method (IsItABarrel) achieves 95.88% balanced accuracy when discriminating among protein classes. Moreover, comparison with IsItABarrel revealed a high rate of false positives in previous TMBB algorithms. In addition to being more accurate than previous datasets, our database (available online) contains 1,894,206 bacterial TMBB proteins from 20 evolutionary classes, respectively 17 and 2.2 times larger than the previous sets TMBB-DB and OMPdb. We anticipate that due to its quality and size the database will serve as a useful resource where high quality TMBB sequence data is required. We found that TMBBs can be divided into 10 types, three of which have not been previously reported. We find tremendous variance in proteome percentage among TMBB-containing organisms with some using 6.79% of their proteome for TMBBs and others using as little as 0.27% of their proteome. The distribution of the lengths of the TMBBs is suggestive of previously hypothesized duplication events. In addition, we find that the C-terminal β-signal varies among different classes of bacteria though it is most commonly HyGHyGY+F. However, this β-signal is only characteristic of prototypical TMBBs. The nine non-prototypical barrel types have other C-terminal motifs and it remains to be determined if these alternative motifs facilitate TMBB insertion or perform any other signaling function.Significance StatementOuter membrane proteins (OMPs) control all interactions between Gram negative bacteria and their environments including uptake and efflux of antibiotics. We created an algorithm that identifies bacterial OMPs from sequence. The quality of our algorithm allows us to identify most OMPs (∼1.8 million) from prokaryotic genomes including >240,000 unrelated to previously structurally-resolved OMPs. We identify ten types of OMPs in our database. The largest type’s signal sequence—used for targeting the membrane-insertion machinery—varies by phylogenetic class. All other types of OMPs do not have a related signal sequence, raising new questions of how these proteins fold. Our web-accessible database will allow for further exploration of the varieties of outer membrane proteins to uncover new targets for controlling antibiotic resistance.
Building a Tissue-unbiased Brain Template of Fibre Orientation Distribution and Tractography with Multimodal Registration
Authors: Lv Jinglei , Zeng Rui , Ho Mai Phuong , D’Souza Arkiev , Calamante Fernando 
Published: April 2022

AbstractA brain template provides a standard space for statistical analysis of brain structure and function. For decades, the T1- and T2-weighted brain templates have been widely used for brain grey matter anatomical and functional analysis. However, T1- and T2-weighted templates provide very limited information about the axonal organization within the white matter. Recent advances in Diffusion MRI have enabled the detailed modelling of the axonal fibre orientation distribution (FOD) in white matter. Therefore, building a FOD template is essential for more robust white matter anatomy related analysis; however, it is important that this template aligns well with the cortical and subcortical structures. From such a FOD template, a tractography template can be also generated by fibre tracking algorithms, which can be used for subsequent applications, such as to perform the joint structural and functional analysis while ensuring rigorous fibre-to-fibre correspondence. In this paper, we explore the potential of generating the FOD template based on multimodal registration, in order to constrain the tempalte unbiased to both white and grey matter. We combine the information from T1-weighted, T2-weighted and Diffusion MRI to generate a coherent transformation for FOD registration and template generation. Our FOD template preserves the structural details at the white-grey matter boundary. To illustrate the benefit of this new approach, the resulting tractography template was used for joint structural-functional connectivity analysis.
Assignment of structural transitions during mechanical unwrapping of nucleosomes and their disassembly products
Authors: Díaz-Celis César , Cañari-Chumpitaz Cristhian , Sosa Robert P. , Castillo Juan P. , Zhang Meng , Cheng Enze , Chen Andy , Vien Michael , Kim JeongHoon , Onoa Bibiana , Bustamante Carlos 
Published: April 2022

AbstractNucleosome DNA unwrapping and its disassembly into hexasomes and tetrasomes is necessary for genomic access and plays an important role in transcription regulation. Previous single-molecule mechanical nucleosome unwrapping revealed a low- and a high-force transitions, and force-FRET pulling experiments showed that DNA unwrapping is asymmetrical occurring always first from one side before the other. However, the assignment of DNA segments involved in these transitions remains controversial. Here, using high-resolution optical tweezers with simultaneous single-molecule FRET detection we show that the low-force transition corresponds to the undoing of the outer-wrap of one side of the nucleosome (~27 bp), a process that can occur either cooperatively or non-cooperatively, whereas the high-force transition corresponds to the simultaneous unwrapping of ~76 bp from both sides. This process may give rise stochastically to the disassembly of nucleosomes into hexasomes and tetrasomes whose unwrapping/rewrapping trajectories we establish. In contrast, nucleosome rewrapping does not exhibit asymmetry. To rationalize all previous nucleosome unwrapping experiments, it is necessary to invoke that mechanical unwrapping involves two nucleosome reorientations: one that contributes to the change in extension at the low-force transition, and another that coincides but does not contribute to the high-force transition.Significance statementNucleosomes, the fundamental structural unit of chromatin, consists of ~147 DNA base pairs wrapped around a histone protein octamer. Determining the forces required to unwrap the DNA from the core particle and the stepwise transitions involved in the process are essential to characterize the strength of the nucleosomal barrier and its contribution as a mechanism of control of gene expression. Here, we performed combined optical tweezers and single-molecule fluorescence measurements to annotate the specific DNA segments unwrapping during the force transitions observed in mechanical unwrapping of nucleosomes. Furthermore, we characterize the mechanical signatures of subnucleosomal particles: hexasomes and tetrasomes. The characterization performed in this work is essential for the interpretation of ongoing studies of chromatin remodelers, polymerases, and histone chaperones.