bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved drug–target interaction prediction with intermolecular graph transformer
Authors: Liu Siyuan , Wang Yusong , Deng Yifan , He Liang , Shao Bin , Yin Jian , Zheng Nanning , Liu Tie-Yan , Wang Tong
Published: April 2022

The identification of active binding drugs for target proteins (referred to as drug–target interaction prediction) is the key challenge in virtual screening, which plays an essential role in drug discovery. Although recent deep learning-based approaches achieve better performance than molecular docking, existing models often neglect topological or spatial of intermolecular information, hindering prediction performance. We recognize this problem and propose a novel approach called the Intermolecular Graph Transformer (IGT) that employs a dedicated attention mechanism to model intermolecular information with a three-way Transformer-based architecture. IGT outperforms state-of-the-art (SoTA) approaches by 9.1% and 20.5% over the second best option for binding activity and binding pose prediction, respectively, and exhibits superior generalization ability to unseen receptor proteins than SoTA approaches. Furthermore, IGT exhibits promising drug screening ability against severe acute respiratory syndrome coronavirus 2 by identifying 83.1% active drugs that have been validated by wet-lab experiments with near-native predicted binding poses. Source code and datasets are available at https://github.com/microsoft/IGT-Intermolecular-Graph-Transformer.
ReadBouncer: precise and scalable adaptive sampling for nanopore sequencing
Authors: Ulrich Jens-Uwe , Lutfi Ahmad , Rutzen Kilian , Renard Bernhard Y
Published: April 2022

Motivation

Nanopore sequencers allow targeted sequencing of interesting nucleotide sequences by rejecting other sequences from individual pores. This feature facilitates the enrichment of low-abundant sequences by depleting overrepresented ones in-silico. Existing tools for adaptive sampling either apply signal alignment, which cannot handle human-sized reference sequences, or apply read mapping in sequence space relying on fast graphical processing units (GPU) base callers for real-time read rejection. Using nanopore long-read mapping tools is also not optimal when mapping shorter reads as usually analyzed in adaptive sampling applications.

Results

Here, we present a new approach for nanopore adaptive sampling that combines fast CPU and GPU base calling with read classification based on Interleaved Bloom Filters. ReadBouncer improves the potential enrichment of low abundance sequences by its high read classification sensitivity and specificity, outperforming existing tools in the field. It robustly removes even reads belonging to large reference sequences while running on commodity hardware without GPUs, making adaptive sampling accessible for in-field researchers. Readbouncer also provides a user-friendly interface and installer files for end-users without a bioinformatics background.

Availability and implementation

The C++ source code is available at https://gitlab.com/dacs-hpi/readbouncer.

Supplementary information

Supplementary data are available at Bioinformatics online.
MeConcord: a new metric to quantitatively characterize DNA methylation heterogeneity across reads and CpG sites
Authors: Zhang Xianglin , Wang Xiaowo
Published: April 2022

Motivation

Intermediately methylated regions occupy a significant fraction of the human genome and are closely associated with epigenetic regulations or cell-type deconvolution of bulk data. However, these regions show distinct methylation patterns, corresponding to different biological mechanisms. Although there have been some metrics developed for investigating these regions, the high noise sensitivity limits the utility for distinguishing distinct methylation patterns.

Results

We proposed a method named MeConcord to measure local methylation concordance across reads and CpG sites, respectively. MeConcord showed the most stable performance in distinguishing distinct methylation patterns (‘identical’, ‘uniform’ and ‘disordered’) compared with other metrics. Applying MeConcord to the whole genome data across 25 cell lines or primary cells or tissues, we found that distinct methylation patterns were associated with different genomic characteristics, such as CTCF binding or imprinted genes. Further, we showed the differences of CpG island hypermethylation patterns between senescence and tumorigenesis by using MeConcord. MeConcord is a powerful method to study local read-level methylation patterns for both the whole genome and specific regions of interest.

Availability and implementation

MeConcord is available at https://github.com/WangLabTHU/MeConcord.

Supplementary information

Supplementary data are available at Bioinformatics online.
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

Motivation

In 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.

Results

Here, 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 implementation

The 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 information

Supplementary 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

Motivation

Genome 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.

Results

We 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 implementation

The 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 information

Supplementary 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

Motivation

Understanding 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.

Results

We 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 implementation

Code is available publicly at https://github.com/phineasng/DECODE.

Supplementary information

Supplementary data are available at Bioinformatics online.
Physiology restores purpose to evolutionary biology
Authors: Noble Raymond , Noble Denis
Published: April 2022

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

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

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

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

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

Background

The 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).

Methods

A 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.

Results

Some 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.

Conclusion

There 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

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 < 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 > 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

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

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 < 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.
Rediscovery of the Galapagos endemic Lecocarpus leptolobus (Asteraceae), its morphology, distribution and taxonomy relative to its congeners
Authors: Tye Alan , Jaramillo Díaz Patricia
Published: April 2022

We report the rediscovery of Lecocarpus leptolobus at its type locality, and restrict the latter to El Ripioso, San Cristóbal, Galapagos. We compare the morphology of the population at this site with other populations of Lecocarpus on San Cristóbal and other Galapagos islands. We conclude that L. leptolobus is a valid taxon endemic to the south-western half of San Cristóbal and is not synonymous with L. lecocarpoides, whereas populations further north-east on the same island constitute a separate species validly named L. darwinii. These two taxa support the idea of a former biogeographic barrier between the two halves of San Cristóbal. Plants at two of the easternmost localities of the south-western species show some characters intermediate between the two species, possibly representing introgression following easing of the barrier. The three specimens of Lecocarpus collected on San Cristóbal by Charles Darwin, all mounted on a single herbarium sheet, comprise one branch of L. leptolobus and two of L. darwinii. We identify possible sites for Darwin’s collections based on information about his explorations. We find grounds for accepting the taxon Acanthospermum brachyceratum as a subspecies of L. lecocarpoides endemic to Gardner-by-Española, Osborn and Xarifa islets, the first of these being the type locality, demonstrating that even narrow sea barriers can contribute to plant radiation in oceanic archipelagos. On the basis of our findings, we provide a new key to the taxa of Lecocarpus.
LUtarjet-limit unique coracoid osteotomy Latarjet (With video)
Authors: Deng Zhenhan , Long Zeling , Lu Wei
Published: April 2022

Background

The Latarjet procedure is an effective technique for the treatment of recurrent anterior shoulder dislocation with glenoid bone loss. However, the inevitable destruction of the coracoacromial arch may result in humeral head translation. The aim of the study is to introduce a modified Latarjet technique with coracoacromial arch preservation as well as its short term clinical outcomes.

Methods

We propose a novel individualized flexible arthroscopic suture button fixation Latarjet technique called `LUtarjet' with video. Precise measurements of the coracoid process, glenoid deficiency and osteotomy plane were made preoperatively. Only three arthroscopic portals were needed and limit unique coracoid osteotomy was performed with coracoacromial arch preservation. The mini window splitting of the subscapularis was performed from the posterior to the anterior direction and the split window was as small as 8–10 mm in length.

Results

A total of 27 patients (25.6 ± 5.4 years) were included in the study. The average surgical duration was 55.6 ± 6.3 min and the mean follow-up time was 8.1 ± 1.5 months. The functional score was significantly improved at the last follow-up. Radiologic evidence showed that the bone graft healing was placed in the desired position. No complications were found.

Conclusions

We present a fast, easy, accurate, safe arthroscopic ‘LUtarjet’ technique called FEAST that can simplify the arthroscopic Latarjet process and achieve a satisfactory bone graft position and satisfactory short-term clinical outcomes.

Level of evidence

IV, case series.
Extractive Humanitarianism: Participatory Confinement and Unpaid Labor in Refugees Governmentality
Authors: Tazzioli Martina
Published: April 2022

This article advances the notion of “extractive humanitarianism” to designate the role played by data extraction and knowledge extraction operations in refugee governmentality. It argues that extractive operations rely on refugees’ active participation to their own governmentality—what I define as participatory confinement. The piece engages with feminist literature on unpaid labor and shows that participatory confinement implies that refugees perform unpaid labor activities, which are disguised as voluntary work. It moves on by conceptualizing participatory confinement through the lens of the invitation to governmentality. In order to develop this, the article focuses on two modes of participatory confinement: unpaid labor that asylum seekers do as “voluntary” activities and knowledge and data extraction. It concludes by questioning extractive humanitarianism in light of the subtle coercion and invisible exploitation that asylum seekers are exposed to.
Rapid invisible frequency tagging (RIFT): a promising technique to study neural and cognitive processing using naturalistic paradigms
Authors: Seijdel Noor , Marshall Tom R , Drijvers Linda
Published: April 2022

Frequency tagging has been successfully used to investigate selective stimulus processing in electroencephalography (EEG) or magnetoencephalography (MEG) studies. Recently, new projectors have been developed that allow for frequency tagging at higher frequencies (>60 Hz). This technique, rapid invisible frequency tagging (RIFT), provides two crucial advantages over low-frequency tagging as (i) it leaves low-frequency oscillations unperturbed, and thus open for investigation, and ii) it can render the tagging invisible, resulting in more naturalistic paradigms and a lack of participant awareness. The development of this technique has far-reaching implications as oscillations involved in cognitive processes can be investigated, and potentially manipulated, in a more naturalistic manner.
Simultaneous Estimation of Telmisartan, Chlorthalidone, Amlodipine Besylate and Atorvastatin by RP-HPLC Method for Synchronous Assay of Multiple FDC Products Using Analytical FMCEA-Based AQbD Approach
Authors: Prajapati Pintu , Patel Ankita , Shah Shailesh
Published: April 2022

Numerous reversed-phase high-pressure liquid chromatography (RP-HPLC) and high-performance thin-layer chromatography (HPTLC) techniques have been published for the estimation of fixed-dose combinations (FDCs) of telmisartan (TEL). No published literature has been reported to date which described the synchronous estimation of FDCs of TEL using a single chromatography condition. Hence, the RP-HPLC method has been developed and validated for synchronous analysis of FDCs of TEL using an enhanced analytical quality by design (AQbD) approach to save time, cost and solvent for analysis. The implementation of AQbD was initiated with the identification of failure modes (FMs) using the Ishikawa diagram, and their critical effect analysis was carried out by risk priority number ranking and filtering method. The identified critical FMs were optimized by design of experiments-based response surface modeling using the Box–Behnken design. The method operable design region was navigated and control strategy was framed to mitigate the risk of critical FM. The RP-HPLC method was developed using Shim-Pack octadecyl silane C18 column and acetonitrile: 1.0%v/v triethylamine (pH 6.5 adjusted using perchloric acid; 42:58, %v/v). The developed method was found to be validated as per the International Council For Harmonization Q2 (R1) guideline. The method was applied for the synchronous assay of seven different FDCs of TEL and assay results were found in good compliance with the respective labeled claim.
Synthesis of Molecularly Imprinted Polymers Based on a New Monomer “2-(4-Vinylphenyl) Quinoline-4-Carboxylic Acid” for the Selective Solid-Phase Extraction of Lamotrigine
Authors: Yin Deng-Yang , Lyu Nan , Qian Zeng-Ting , Zhao Lin-Lin , Wang Liang , Tang Dao-Quan , Du Yan
Published: April 2022

A new molecularly imprinted polymers (MIPs) have been prepared for the high selective extraction of lamotrigine (LTG), a widely used antiepileptic drug, in human serum. The MIPs were polymerized by bulk polymerization using our synthesized compound, 2-(4-vinylphenyl) quinolin-4-carboxylic acid, as functional monomer, which achieved better adsorption specificity than universal MIPs. Then, the molecularly imprinted solid phase extraction (MISPE) based on this material was coupled with high-performance liquid chromatography (HPLC) for the detection of LTG in human serum. The results of method validation showed that the developed method presented a good precision and accuracy, and the linearity was in the range of 1.50–40.00 mg/mL with the limit of quantitation (LOQ) at 0.20 mg/mL. The recovery ranged from 80.8% to 83.8% with RSD ranges from 5.5% to 11.1%. The validated method was successfully used to determine the concentration of LTG in human simulate serum samples.
Coronavirus Disease 2019 Vaccine Trials (and Tribulations): How to Improve the Process of Clinical Trials in a Pandemic
Authors: Sherman Amy C , Rouphael Nadine , Baden Lindsey R
Published: April 2022

Vaccine clinical trials have been essential to developing effective severe acute respiratory syndrome coronavirus 2 vaccines. The challenges of supply chain disruptions, infection control, study designs, and participant factors that affect trial procedures are reviewed, with specific solutions to streamline the clinical trial process.
From globalising to regionalising to reshoring value chains? The case of Japan’s semiconductor industry
Authors: Kamakura Natsuki
Published: April 2022

This study evaluates the current situation and challenges of reshoring in the Japanese manufacturing industry, focusing on the semiconductor industry, which once dominated the world. After a recent document analysis and qualitative interviews with firms’ representatives and policymakers, it is apparent that the globalised semiconductor industry is unlikely to reshore to Japan even amid supply chain disruptions due to the coronavirus disease 2019 pandemic. A review of Japan’s semiconductor-related industries, such as semiconductor manufacturing materials, validated that they are embedded in Asian production networks and need to be optimised within a regionalised production system.
Regionalisation or domesticalisation? Configurations of China’s emerging domestic market-driven industrial robot production networks
Authors: Fu Tianlan , Cheng Yeqing
Published: April 2022

From global production network (GPN) theory, this study explores the configurations of emerging Southern market-driven production networks through the case of China’s industrial robot industry which has emerged with increasing automation in production. This paper argues that to serve the Chinese high- and middle-end customers, global lead firms from Western economies have established regional production networks by localising production, connecting with global component suppliers in/outside China and collaborating with Chinese system integrators. However, Chinese capable firms have organised domestic production networks for the low and middle-end through integrating with domestic component suppliers and system integrators. This study adapts the GPN framework, mostly highlighting Western markets, by examining markets and firms in the Global South and revealing new configurations of production networks.
Tasks, occupations and slowbalisation: on the limits of fragmentation
Authors: Brakman Steven , van Marrewijk Charles
Published: April 2022

Following the trade collapse in 2009, Globalisation has recovered but the growth rate slowed down compared to the preceding period of Hyper Globalisation. The persistence of this slowdown is remarkable. We argue that increased awareness of firms for the costs of involvement in global supply chains can explain the recent developments in trade flows. We formalise the existence, length and consequences of changes in fragmentation cost along global supply chains. From a theoretical point of view, we allow tasks to be a combination of different occupations while the model endogenises production fragmentation, allowing for multiple production stages in multiple countries, while remaining tractable. From an empirical point of view, the model explains both the period of Hyper Globalisation and the subsequent Slowbalisation in terms of changing fragmentation costs along global supply chains. The model is also consistent with developments regarding labour market polarisation associated with modern globalisation: the labour market position of medium-skilled workers in advanced countries has deteriorated relative to high- and low-skilled workers, which can be understood by changing global supply chains. Our model implies, however, that even with zero fragmentation costs the demand for certain occupations does not fall to zero for any country.
Kidney–placenta crosstalk in health and disease
Authors: Cabarcas-Barbosa Omar , Capalbo Olivia , Ferrero-Fernández Alberta , Musso Carlos G
Published: April 2022

Organ crosstalk allows the interaction between systems to adapt to a constant changing environment, maintaining homeostasis. The process of placentation and the new hormonal environment during pregnancy trigger physiological changes that modulate kidney function to control extracellular volume, acid–base balance and filtration of metabolic waste products. The bidirectional communication means that acute or chronic dysfunction of one organ can compromise the other. Abnormal placentation in pregnancy-related hypertensive disorders such as pre-eclampsia and HELLP (haemolysis, elevated liver enzymes and low platelet count) syndrome leads to the release of antiangiogenic factors that may cause kidney injury (thrombotic microangiopathy, glomeruloendotheliosis, mesangiolysis and vasoconstriction of peritubular vessels). These hypertensive disorders are a key cause of kidney injury in gestation, which increases maternal morbimortality and adverse foetal outcomes. Conversely, prior kidney injury or causes of kidney injury (diabetes, lupus, glomerulonephritis or other forms of chronic kidney disease) increase the risk of developing hypertensive pregnancy disorders, providing a baseline higher risk. Inherited kidney diseases are a special concern, given the potential for genetic predisposition to kidney disease in the foetus. Understanding the bidirectional potential for compromise from placenta to kidney and vice versa provides a better framework to limit damage to both organs and improve maternal and foetal outcomes.
Expert guidance on the multidisciplinary management of cystinosis in adolescent and adult patients
Authors: Levtchenko Elena , Servais Aude , Hulton Sally A , Ariceta Gema , Emma Francesco , Game David S , Lange Karin , Lapatto Risto , Liang Hong , Sberro-Soussan Rebecca , Topaloglu Rezan , Das Anibh M , Webb Nicholas J A , Wanner Christoph
Published: April 2022

Cystinosis, a rare autosomal recessive lysosomal storage disorder, results in an abnormal accumulation of the amino acid cystine in multiple organs and tissues of the body. Renal symptoms typically develop in the first few months of life, with extra-renal manifestations becoming apparent over the next 10–20 years, which require coordinated multidisciplinary care. Here, we describe a consensus-based guidance to support the management of adolescents and adults living with cystinosis. The programme was led by a Steering Committee (SC) of six experts in the management of patients with cystinosis, who identified a list of 15 key questions reflecting the multi-organ effects of cystinosis. An Extended Faculty (EF) of eight additional specialists was invited to answer the questions via an online digital platform using a quasi-Delphi approach. The consolidated answers were summarized into recommendations. Where evidence was lacking, recommendations were developed using collective expert consensus. The EF was asked to agree/disagree with the clinical recommendations. The expert-agreed clinical recommendations provide guidance that considers both renal and extra-renal systems. The topics covered are advice on fertility and family planning, consideration of the nervous, muscular, ophthalmic, cardio-respiratory, endocrine, dermatological and gastrointestinal systems, as well as guidance on dental care, diet, lifestyle, and improving quality of life and psychological well-being. In summary, this work outlines recommendations and a checklist for clinicians with a vision for improving and standardizing the multidisciplinary care for patients with cystinosis.
Learning Disjunctive Multiplicity Expressions and Disjunctive Generalize Multiplicity Expressions From Both Positive and Negative Examples
Authors: Li Yeting , Chen Haiming , Chen Zixuan
Published: April 2022

The presence of a schema for eXtensible Markup Language (XML) documents has numerous advantages. Unfortunately, many XML documents in practice are not accompanied by a (valid) schema. Therefore, it is essential to devise algorithms to infer schemas from XML documents, where the fundamental task is learning regular expressions. In this paper, we focus on the learning of disjunctive multiplicity expressions (DMEs), a subclass of regular expressions that are particularly suitable to specify unordered models and have been used as the foundation of the schemas for unordered XML. Previous work for learning DME lacks inference algorithms that support positive and negative examples. Further, presently there has been no algorithm can learn DMEs extended with numeric occurrences. We address these challenges in the present paper and first propose a novel algorithm to learn DMEs from positive and negative examples by using genetic algorithms and parallel techniques. Then we extend DMEs to disjunctive generalized multiplicity expressions (DGMEs), which allow numeric occurrences and develop an algorithm to learn DGMEs from positive and negative examples. Finally, experimental results show that with only positive examples, our algorithm can generate a DME with an acceptable learning time, which can accept all positive examples, and when given both positive and negative examples, we can learn DMEs or DGMEs with high accuracy.
Hamiltonian Properties of the Data Center Network HSDC with Faulty Elements
Authors: Dong Hui , Fan Jianxi , Cheng Baolei , Wang Yan , Xu Li
Published: April 2022

The data center network HSDC is a superior candidate for building large-scale data centers, and strikes a good balance among diameter, bisection width, incremental scalability and other important characteristics in contrast to the state-of-the-art data center network architectures. The Hamiltonian property is an important indicator to measure the reliability of a network. In this paper, we study the Hamiltonian properties of HSDC’s logic graph $H_n$. Firstly, we prove that $H_n$ is Hamiltonian-connected for $n\geq 3$. Secondly, we propose an $O(NlogN)$ algorithm for finding a Hamiltonian path between any two distinct nodes in $H_n$, where $N$ is the number of nodes in $H_n$. Furthermore, we consider the Hamiltonian properties of $H_n$ with faulty elements, and prove that $H_n$ is $(n-3)$-fault-tolerant Hamiltonian-connected and $(n-2)$-fault-tolerant Hamiltonian for $n\geq 3$.
The Homeric Διὸς ἀπάτη and its reuse within the seventeenth-century Portuguese epic poemUlisseia ou Lisboa Edificada
Authors: Fonseca Rui Carlos
Published: April 2022

Ulisseia ou Lisboa Edificada (Ulysseia or Lisbon Founded) is a seventeenth-century epic poem written by Gabriel Pereira de Castro, which celebrates the mythical arrival of Ulysses in Lusitania and the subsequent foundation of Ulisseia by him. This city built by Greek hands comes to be Lisbon, the head of a great navy empire at the time of Portuguese Discoveries. This epic reshapes both the Odyssean sea voyages and Iliadic warfare, whereas Ulysses, the same crafty wanderer as the Homeric Odysseus, is also the bearer of a god-given mission like the Virgilian Aeneas. In this article, I examine the refashioning of the Homeric Διὸς ἀπάτη (‘Deception of Zeus’) in Ulisseia book 10 from a comparative and literary perspective. Castro follows his Greek model very closely, but at the same time it departs from it in important ways. In portraying the deceitful planning of Hera, with its erotic and humorous tone, he adapts it to the nationalistic purposes of his own epic story. Juno’s plan is granted a more serious tone, since its effects on the war between Greeks and Lusitanians are directly linked to the glorious Destiny of the Portuguese people.