bluuebunny/crossref_metadata_2025_split huggingface dataset:
A LASSO-based approach to sample sites for phylogenetic tree search
Authors: Ecker Noa , Azouri Dana , Bettisworth Ben , Stamatakis Alexandros , Mansour Yishay , Mayrose Itay , Pupko Tal 
Published: April 2022

AbstractMotivationIn recent years, full-genome sequences have become increasingly available and as a result many modern phylogenetic analyses are based on very long sequences, often with over 100 000 sites. Phylogenetic reconstructions of large-scale alignments are challenging for likelihood-based phylogenetic inference programs and usually require using a powerful computer cluster. Current tools for alignment trimming prior to phylogenetic analysis do not promise a significant reduction in the alignment size and are claimed to have a negative effect on the accuracy of the obtained tree.ResultsHere, we propose an artificial-intelligence-based approach, which provides means to select the optimal subset of sites and a formula by which one can compute the log-likelihood of the entire data based on this subset. Our approach is based on training a regularized Lasso-regression model that optimizes the log-likelihood prediction accuracy while putting a constraint on the number of sites used for the approximation. We show that computing the likelihood based on 5% of the sites already provides accurate approximation of the tree likelihood based on the entire data. Furthermore, we show that using this Lasso-based approximation during a tree search decreased running-time substantially while retaining the same tree-search performance.Availability and implementationThe code was implemented in Python version 3.8 and is available through GitHub (https://github.com/noaeker/lasso_positions_sampling). The datasets used in this paper were retrieved from Zhou et al. (2018) as described in section 3.Supplementary informationSupplementary data are available at Bioinformatics online.
Markov chains improve the significance computation of overlapping genome annotations
Authors: Gafurov Askar , Brejová Broňa , Medvedev Paul 
Published: April 2022

AbstractMotivationGenome annotations are a common way to represent genomic features such as genes, regulatory elements or epigenetic modifications. The amount of overlap between two annotations is often used to ascertain if there is an underlying biological connection between them. In order to distinguish between true biological association and overlap by pure chance, a robust measure of significance is required. One common way to do this is to determine if the number of intervals in the reference annotation that intersect the query annotation is statistically significant. However, currently employed statistical frameworks are often either inefficient or inaccurate when computing P-values on the scale of the whole human genome.ResultsWe show that finding the P-values under the typically used ‘gold’ null hypothesis is NP-hard. This motivates us to reformulate the null hypothesis using Markov chains. To be able to measure the fidelity of our Markovian null hypothesis, we develop a fast direct sampling algorithm to estimate the P-value under the gold null hypothesis. We then present an open-source software tool MCDP that computes the P-values under the Markovian null hypothesis in O(m2+n) time and O(m) memory, where m and n are the numbers of intervals in the reference and query annotations, respectively. Notably, MCDP runtime and memory usage are independent from the genome length, allowing it to outperform previous approaches in runtime and memory usage by orders of magnitude on human genome annotations, while maintaining the same level of accuracy.Availability and implementationThe software is available at https://github.com/fmfi-compbio/mc-overlaps. All data for reproducibility are available at https://github.com/fmfi-compbio/mc-overlaps-reproducibility.Supplementary informationSupplementary data are available at Bioinformatics online.
DECODE: a computational pipeline to discover T cell receptor binding rules
Authors: Papadopoulou Iliana , Nguyen An-Phi , Weber Anna , Martínez María Rodríguez 
Published: April 2022

AbstractMotivationUnderstanding the mechanisms underlying T cell receptor (TCR) binding is of fundamental importance to understanding adaptive immune responses. A better understanding of the biochemical rules governing TCR binding can be used, e.g. to guide the design of more powerful and safer T cell-based therapies. Advances in repertoire sequencing technologies have made available millions of TCR sequences. Data abundance has, in turn, fueled the development of many computational models to predict the binding properties of TCRs from their sequences. Unfortunately, while many of these works have made great strides toward predicting TCR specificity using machine learning, the black-box nature of these models has resulted in a limited understanding of the rules that govern the binding of a TCR and an epitope.ResultsWe present an easy-to-use and customizable computational pipeline, DECODE, to extract the binding rules from any black-box model designed to predict the TCR-epitope binding. DECODE offers a range of analytical and visualization tools to guide the user in the extraction of such rules. We demonstrate our pipeline on a recently published TCR-binding prediction model, TITAN, and show how to use the provided metrics to assess the quality of the computed rules. In conclusion, DECODE can lead to a better understanding of the sequence motifs that underlie TCR binding. Our pipeline can facilitate the investigation of current immunotherapeutic challenges, such as cross-reactive events due to off-target TCR binding.Availability and implementationCode is available publicly at https://github.com/phineasng/DECODE.Supplementary informationSupplementary data are available at Bioinformatics online.
Physiology restores purpose to evolutionary biology
Authors: Noble Raymond , Noble Denis 
Published: April 2022

Abstract
Life is purposefully creative in a continuous process of maintaining integrity; it adapts to counteract change. This is an ongoing, iterative process. Its actions are essentially directed to this purpose. Life exists to exist. Physiology is the study of purposeful living function. Function necessarily implies purpose. This was accepted all the way from William Harvey in the 17th century, who identified the purpose of the heart to pump blood and so feed the organs and tissues of the body, through many 19th and early 20th century examples. But late 20th century physiology was obliged to hide these ideas in shame. Teleology became the ‘lady who no physiologist could do without, but who could not be acknowledged in public.’ This emasculation of the discipline accelerated once the Central Dogma of molecular biology was formulated, and once physiology had become sidelined as concerned only with the disposable vehicle of evolution. This development has to be reversed. Even on the practical criterion of relevance to health care, gene-centrism has been a disaster, since prediction from elements to the whole system only rarely succeeds, whereas identifying whole system functions invariably makes testable predictions at an elemental level.
Automated splitting into batches for observational biomedical studies with sequential processing
Authors: Burger Bram , Vaudel Marc , Barsnes Harald 
Published: April 2022

Summary
Experimental design usually focuses on the setting where treatments and/or other aspects of interest can be manipulated. However, in observational biomedical studies with sequential processing, the set of available samples is often fixed, and the problem is thus rather the ordering and allocation of samples to batches such that comparisons between different treatments can be made with similar precision. In certain situations, this allocation can be done by hand, but this rapidly becomes impractical with more challenging cohort setups. Here, we present a fast and intuitive algorithm to generate balanced allocations of samples to batches for any single-variable model where the treatment variable is nominal. This greatly simplifies the grouping of samples into batches, makes the process reproducible, and provides a marked improvement over completely random allocations. The general challenges of allocation and why good solutions can be hard to find are also discussed, as well as potential extensions to multivariable settings.
DIAgnostic iMaging or Observation in early equivocal appeNDicitis (DIAMOND): open-label, randomized clinical trial
Authors: Lastunen Kirsi S. , Leppäniemi Ari K. , Mentula Panu J. 
Published: April 2022

Abstract

Background
Mild appendicitis may resolve spontaneously. The use of CT may lead to an overdiagnosis of uncomplicated appendicitis. The aims of this study were to examine whether early imaging results in more patients being diagnosed with acute appendicitis than initial observation, and to study the safety and feasibility of score-based observation compared with imaging in patients with equivocal signs of appendicitis.

Methods
Patients with suspected appendicitis with symptoms for fewer than 24 h and an Adult Appendicitis Score of 11–15 were eligible for this trial. After exclusions, patients were randomized openly into two equal-sized groups: imaging and observation. Patients in the imaging group had ultrasound imaging followed by CT when necessary, whereas those in the observation group were reassessed after 6–8 h with repeated scoring and managed accordingly. The primary outcome was the number of patients requiring treatment for acute appendicitis within 30 days.

Results
Ninety-three patients were randomized to imaging and 92 to observation; after exclusions, 93 and 88 patients respectively were analysed. In the imaging group, more patients underwent treatment for acute appendicitis than in the observation group: 72 versus 57 per cent (difference 15 (95 per cent c.i. 1 to 29) per cent). This suggests that patients with spontaneously resolving appendicitis were not diagnosed or treated in the observation group. Some 55 per cent of patients in the observation group did not need diagnostic imaging within 30 days after randomization. There was no difference in the number of patients diagnosed with complicated appendicitis (4 versus 2 per cent) or negative appendicectomies (1 versus 1 per cent) in the imaging and observation groups.

Conclusion
Score-based observation of patients with early equivocal appendicitis results in fewer patients requiring treatment for appendicitis. Registration number: NCT02742402 (http://www.clinicaltrials.gov).
Effect of prucalopride to improve time to gut function recovery following elective colorectal surgery: randomized clinical trial
Authors: Milne Tony , Liu Chen , O’Grady Greg , Woodfield John , Bissett Ian 
Published: April 2022

Abstract

Background
Delayed return to gut function and prolonged postoperative ileus (PPOI) delay recovery after colorectal surgery. Prucalopride is a selective serotonin-4-receptor agonist that may improve gut motility.

Methods
This was a multicentre, double-blind, parallel, placebo-controlled randomized trial of 2 mg prucalopride versus placebo in patients undergoing elective colorectal resection. Patients with inflammatory bowel disease and planned ileostomy formation were excluded, but colostomy formation was allowed. The study medication was given 2 h before surgery and daily for up to 6 days after operation. The aim was to determine whether prucalopride improved return of gut function and reduced the incidence of PPOI. The primary endpoint was time to passage of stool and tolerance of diet (GI-2). Participants were allocated in a 1 : 1 ratio, in blocks of 10. Randomization was computer-generated. All study personnel, medical staff, and patients were blinded.

Results
This study was completed between October 2017 and May 2020 at two tertiary hospitals in New Zealand. A total of 148 patients were randomized, 74 per arm. Demographic data were similar in the two groups. There was no difference in median time to GI-2 between prucalopride and placebo groups: 3.5 (i.q.r. 2–5) versus 4 (3–5) days respectively (P = 0.124). Prucalopride improved the median time to passage of stool (3 versus 4 days; P = 0.027) but not time to tolerance of diet (2 versus 2 days; P = 0.669) or median duration of hospital stay (4 versus 4 days; P = 0.929). In patients who underwent laparoscopic surgery (125, 84.5 per cent), prucalopride improved median time to GI-2: 3 (2–4) days versus 4 (3–5) days for placebo (P = 0.012). The rate of PPOI, complications, and adverse events was similar in the two groups.

Conclusion
Prucalopride did not improve time to overall recovery of gut function after elective colorectal surgery. Registration number: NCT02947269 (http://www.clinicaltrials.gov).
Pancreatic surgery with or without drainage: propensity score-matched study
Authors: Nickel Felix , Lang Franziska , Kowalewski Karl Friedrich , Haney Caelan Max , Menrath Marc , Berchtold Christoph , Hoffmann Katrin , Loos Martin , Mehrabi Arianeb , Probst Pascal , Schmidt Thomas , Schneider Martin , Diener Markus K , Strobel Oliver , Müller-Stich Beat P , Hackert Thilo 
Published: April 2022

Abstract

Background
A recent RCT has shown that routine intraoperative drain placement after pancreatoduodenectomy (PD) is not necessary. The aim was to confirm this in real-world conditions.

Methods
A propensity score-matched (PSM) analysis of patients with and without drainage after PD or distal pancreatectomy (DP) at a high-volume centre was undertaken. Main outcomes were complications and duration of hospital stay. Multivariable regression analysis was used to assessed which factors led to intraoperative drainage after the standard was changed from drain to no drain.

Results
Of 377 patients who underwent PD, 266 were included in PSM analysis. No drain was associated with fewer major complications (42 (31.6 per cent) versus 62 (46.6 per cent); P = 0.017), shorter duration of hospital stay (mean(s.d.) 14.7(8.5) versus 19.6(14.9) days; P = 0.001), and required fewer interventional drain placements (8.4 versus 19.8 per cent; P = 0.013). In PSM analysis after DP (112 patients), no drainage was associated with fewer clinically relevant postoperative pancreatic fistulas (9 versus 18 per cent; P = 0.016), fewer overall complications (mean(s.d.) comprehensive complication index score 15.9(15.4) versus 24.8(20.4); P = 0.012), and a shorter hospital stay (9.3(7.0) versus 13.5(9.9) days; P = 0.011). Multivisceral resection (OR 2.80, 95 per cent c.i. 1.10 to 7.59; P = 0.034) and longer operating times (OR 1.56, 1.04 to 2.36; P = 0.034) influenced the choice to place a drain after PD. Greater blood loss was associated with drainage after DP (OR 1.14, 1.02 to 1.30; P = 0.031).

Conclusion
Standard pancreatic resections can be performed safely without drainage. Surgeons were more reluctant to omit drainage after complex pancreatic resections.
Effect of high-painversuslow-pain structured exercise on walking ability in people with intermittent claudication: meta-analysis
Authors: Perks Jemma , Zaccardi Francesco , Paterson Craig , Houghton John S M , Nickinson Andrew T O , Pepper Coral J , Rayt Harjeet , Yates Thomas , Sayers Robert 
Published: April 2022

AbstractBackgroundThe aim was to determine the comparative benefits of structured high-pain exercise, structured low-pain exercise, and usual-care control, to identify which has the largest effect on walking ability in people with intermittent claudication (IC).MethodsA network meta-analysis was undertaken to assess two outcomes: pain-free walking ability (PFWA) and maximal walking ability (MWA). Nine electronic databases were searched. Trials were included if they were: RCTS; involved adults with IC; had at least two of the following arms—structured low-pain exercise, structured high­-pain exercise or usual-care control; and a maximal or pain-free treadmill walking outcome.ResultsSome 14 trials were included; results were pooled using the standardized mean difference (MD). Structured low-pain exercise had a significant large positive effect on MWA (MD 2.23, 95 percent c.i. 1.11 to 3.35) and PFWA (MD 2.26, 1.26 to 3.26) compared with usual-care control. Structured high-pain exercise had a significant large positive effect on MWA (MD 0.95, 0.20 to 1.70) and a moderate positive effect on PFWA (0.77, 0.01 to 1.53) compared with usual-care control. In an analysis of structured low- versus high pain exercise, there was a large positive effect in favour of low-pain exercise on MWA (MD 1.28, −0.07 to 2.62) and PFWA (1.50, 0.24 to 2.75); however, this was significant only for PFWA.ConclusionThere is strong evidence in support of use of structured high-pain exercise, and some evidence in support of structured low-pain exercise, to improve walking ability in people with IC compared with usual-care control (unstructured exercise advice).
Open versus robotic-assisted laparoscopic posterior component separation in complex abdominal wall repair
Authors: Dewulf Maxime , Hiekkaranta Juha M , Mäkäräinen Elisa , Saarnio Juha , Vierstraete Maaike , Ohtonen Pasi , Muysoms Filip , Rautio Tero 
Published: April 2022

Abstract

Background
Transversus abdominis release (TAR) is a surgical technique used in the treatment of complex ventral hernias. The aim of this study was to compare outcomes of open (oTAR) versus robotic-assisted (rTAR) posterior component separation by TAR.

Methods
Consecutive patients at two European hernia centres who underwent bilateral TAR were included. The primary endpoint was the duration of postoperative hospital stay.

Results
Data from 90 rTAR and 79 oTAR operations were evaluated. Patient demographics were similar between groups in terms of age, sex, BMI, and co-morbidities. There were more smokers, and hernias were larger in the oTAR group (width 8.7 cm versus 10.0 cm; P = 0.031, length 11.6 cm versus 14.1 cm; P = 0.005). Duration of postoperative hospital stay was significantly shorter in the rTAR group (3.4 days versus 6.9 days; P &lt; 0.001). Short-term serious complications (Clavien–Dindo grade III and above) were more frequent (20.3 per cent versus 7.8 per cent; P = 0.018), and there were more surgical site infections (12.7 per cent versus 3.3 per cent; P = 0.010) in the oTAR group. During a median follow-up of 19 months in the rTAR group and 43 months in the oTAR group, reoperation (4.4 per cent versus 8.9 per cent; P = 0.245), and recurrence rates (5.6 per cent versus 5.1 per cent; P &gt; 0.009) were similar.

Conclusion
Patients with ventral incisional hernias who undergo bilateral rTAR had significantly shorter postoperative hospital stays and fewer short-term complications compared with patients undergoing bilateral oTAR.
Patient-reported outcome measures (PROMs) after laparoscopic cholecystectomy: systematic review
Authors: Melly Conor , McGeehan Gearoid , O’Connor Niall , Johnston Alison , Bass Gary , Mohseni Shahin , Donohoe Claire , Bucholc Magda , Sugrue Michael 
Published: April 2022

Abstract

Background
Healthcare requires patient feedback to improve outcomes and experience. This study undertook a systematic review of the depth, variability, and digital suitability of current patient-reported outcome measures (PROMs) in patients undergoing laparoscopic cholecystectomy.

Methods
A PROSPERO-registered (registration number CRD42021261707) systematic review was undertaken for all relevant English language articles using PubMed version of MEDLINE, Scopus, and Web of Science electronic databases in June 2021. The search used Boolean operators and wildcards and included the keywords: laparoscopic cholecystectomy AND patient outcome OR patient-reported outcome OR patient-reported outcome measure OR PRO OR PROM. Medical Subjects Heading terms were used to search PubMed and Scopus. Articles published from 1 January 2011 to 2 June 2021 were included.

Results
A total of 4960 individual articles were reviewed in this study, of which 44 were found to evaluate PROMs in patients undergoing laparoscopic cholecystectomy and underwent methodological index for non-randomized studies (MINORS) grading. Twenty-one articles spanning 19 countries and four continents met all inclusion criteria and were included in the qualitative data synthesis. There was significant heterogeneity in PROMs identified with eight different comprehensive PROM tools used in the 21 studies. There was wide variation in the time points at which PROMs were recorded. Fourteen of 21 studies recorded PROMs before and after surgery, and 7 of 21 recorded PROMs only after surgery. Follow-up intervals ranged from 3 days to 2 years after surgery.

Conclusions
This study identified that while post-laparoscopic cholecystectomy PROMs are infrequently measured currently, tools are widely available to achieve this in clinical practice. PROMs may not capture all the outcomes but should be incorporated into future cholecystectomy outcome research. The EQ-5D™ (EuroQoL Group, Rotterdam, the Netherlands) provides a simple platform for the modern digital era.
The clinical effectiveness of wound edge protectors in reducing surgical site infection after abdominal surgery: meta-analysis
Authors: Li Xujia , Lin Haomin , Zhu Lin , Chen Jing , Lei Sujuan , Li Bo , Su Song 
Published: April 2022

Abstract

Background
Surgical site infection (SSI) is a common complication after abdominal surgery. The effectiveness of wound edge protectors in reducing infection of the surgical sites is still unclear. The purpose of this study was to determine the clinical effectiveness of a wound edge protector (WEP) in reducing SSI rates after abdominal surgery.

Methods
PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched to obtain relevant articles published up to September 2021. Publications were retrieved if they contain primary data on the use of WEPs in reducing SSI compared with standard care in patients undergoing abdominal surgery. Subgroup analyses were performed for different WEP types, surgical sites, and levels of contamination. The outcome of interest was a clinically defined SSI. Qualitative variables were pooled using risk ratios (RRs).

Results
Twenty-two eligible randomized clinical trials involving 4492 patients were included in this meta-analysis. WEP was associated with the reduced incidence of overall SSI (RR = 0.66; 95 per cent c.i. 0.53 to 0.83; P = 0.0003), and superficial SSI (RR = 0.59; 95 per cent c.i. 0.38 to 0.91; P = 0.02). In addition, WEP also successfully reduced the risk of SSI in clean-contaminated wounds (RR = 0.61; 95 per cent c.i. 0.40 to 0.93; P = 0.02) as well as in contaminated wounds (RR = 0.47; 95 per cent c.i. 0.33 to 0.67; P &lt; 0.0001); however, WEP did not reduce SSI incidence in colorectal surgery (RR = 0.68; 95 per cent c.i. 0.46 to 1.01; P = 0.05).

Conclusion
This study suggests that WEP was efficient in reducing superficial SSI. Both double-ringed and single-ringed devices were efficient in reducing SSI. WEP was effective in reducing SSI incidence in clean-contaminated and contaminated surgery; however, its use does not reduce the SSI rate in colorectal surgery.