bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive characterization genetic regulation and chromatin landscape of enhancer-associated long non-coding RNAs and their implication in human cancer
Authors: Li Xin , Pan Xu , Zhou Hanxiao , Wang Peng , Gao Yue , Shang Shipeng , Guo Shuang , Sun Jie , Xiong Zhiying , Ning Shangwei , Zhi Hui , Li Xia
Published: September 2021

Long non-coding RNAs (lncRNAs) that emanate from enhancer regions (defined as enhancer-associated lncRNAs, or elncRNAs) are emerging as critical regulators in disease progression. However, their biological characteristics and clinical relevance have not been fully portrayed. Here, based on the traditional expression quantitative loci (eQTL) and our optimized residual eQTL method, we comprehensively described the genetic effect on elncRNA expression in more than 300 lymphoblastoid cell lines. Meanwhile, a chromatin atlas of elncRNAs relative to the genetic regulation state was depicted. By applying the maximum likelihood estimate method, we successfully identified causal elncRNAs for protein-coding gene expression reprogramming and showed their associated single nucleotide polymorphisms (SNPs) favor binding of transcription factors. Further epigenome analysis revealed two immune-associated elncRNAs AL662844.4 and LINC01215 possess high levels of H3K27ac and H3K4me1 in human cancer. Besides, pan-cancer analysis of 3D genome, transcriptome, and regulatome data showed they potentially regulate tumor-immune cell interaction through affecting MHC class I genes and CD47, respectively. Moreover, our study showed there exist associations between elncRNA and patient survival. Finally, we made a user-friendly web interface available for exploring the regulatory relationship of SNP-elncRNA-protein-coding gene triplets (http://bio-bigdata.hrbmu.edu.cn/elncVarReg). Our study provides critical mechanistic insights for elncRNA function and illustrates their implications in human cancer.
An overview of machine learning methods for monotherapy drug response prediction
Authors: Firoozbakht Farzaneh , Yousefi Behnam , Schwikowski Benno
Published: September 2021

For an increasing number of preclinical samples, both detailed molecular profiles and their responses to various drugs are becoming available. Efforts to understand, and predict, drug responses in a data-driven manner have led to a proliferation of machine learning (ML) methods, with the longer term ambition of predicting clinical drug responses. Here, we provide a uniquely wide and deep systematic review of the rapidly evolving literature on monotherapy drug response prediction, with a systematic characterization and classification that comprises more than 70 ML methods in 13 subclasses, their input and output data types, modes of evaluation, and code and software availability. ML experts are provided with a fundamental understanding of the biological problem, and how ML methods are configured for it. Biologists and biomedical researchers are introduced to the basic principles of applicable ML methods, and their application to the problem of drug response prediction. We also provide systematic overviews of commonly used data sources used for training and evaluation methods.
High dimensionality reduction by matrix factorization for systems pharmacology
Authors: Mehrpooya Adel , Saberi-Movahed Farid , Azizizadeh Najmeh , Rezaei-Ravari Mohammad , Saberi-Movahed Farshad , Eftekhari Mahdi , Tavassoly Iman
Published: September 2021

The extraction of predictive features from the complex high-dimensional multi-omic data is necessary for decoding and overcoming the therapeutic responses in systems pharmacology. Developing computational methods to reduce high-dimensional space of features in in vitro, in vivo and clinical data is essential to discover the evolution and mechanisms of the drug responses and drug resistance. In this paper, we have utilized the matrix factorization (MF) as a modality for high dimensionality reduction in systems pharmacology. In this respect, we have proposed three novel feature selection methods using the mathematical conception of a basis for features. We have applied these techniques as well as three other MF methods to analyze eight different gene expression datasets to investigate and compare their performance for feature selection. Our results show that these methods are capable of reducing the feature spaces and find predictive features in terms of phenotype determination. The three proposed techniques outperform the other methods used and can extract a 2-gene signature predictive of a tyrosine kinase inhibitor treatment response in the Cancer Cell Line Encyclopedia.
Socket2: a program for locating, visualizing and analyzing coiled-coil interfaces in protein structures
Authors: Kumar Prasun , Woolfson Derek N
Published: September 2021

Motivation

Protein–protein interactions are central to all biological processes. One frequently observed mode of such interactions is the α-helical coiled coil (CC). Thus, an ability to extract, visualize and analyze CC interfaces quickly and without expert guidance would facilitate a wide range of biological research. In 2001, we reported Socket, which locates and characterizes CCs in protein structures based on the knobs-into-holes (KIH) packing between helices in CCs. Since then, studies of natural and de novo designed CCs have boomed, and the number of CCs in the RCSB PDB has increased rapidly. Therefore, we have updated Socket and made it accessible to expert and nonexpert users alike.

Results

The original Socket only classified CCs with up to six helices. Here, we report Socket2, which rectifies this oversight to identify CCs with any number of helices, and KIH interfaces with any of the 20 proteinogenic residues or incorporating nonnatural amino acids. In addition, we have developed a new and easy-to-use web server with additional features. These include the use of NGL Viewer for instantly visualizing CCs, and tabs for viewing the sequence repeats, helix-packing angles and core-packing geometries of CCs identified and calculated by Socket2.

Availability and implementation

Socket2 has been tested on all modern browsers. It can be accessed freely at http://coiledcoils.chm.bris.ac.uk/socket2/home.html. The source code is distributed using an MIT licence and available to download under the Downloads tab of the Socket2 home page.
MVGCN: data integration through multi-view graph convolutional network for predicting links in biomedical bipartite networks
Authors: Fu Haitao , Huang Feng , Liu Xuan , Qiu Yang , Zhang Wen
Published: September 2021

Motivation

There are various interaction/association bipartite networks in biomolecular systems. Identifying unobserved links in biomedical bipartite networks helps to understand the underlying molecular mechanisms of human complex diseases and thus benefits the diagnosis and treatment of diseases. Although a great number of computational methods have been proposed to predict links in biomedical bipartite networks, most of them heavily depend on features and structures involving the bioentities in one specific bipartite network, which limits the generalization capacity of applying the models to other bipartite networks. Meanwhile, bioentities usually have multiple features, and how to leverage them has also been challenging.

Results

In this study, we propose a novel multi-view graph convolution network (MVGCN) framework for link prediction in biomedical bipartite networks. We first construct a multi-view heterogeneous network (MVHN) by combining the similarity networks with the biomedical bipartite network, and then perform a self-supervised learning strategy on the bipartite network to obtain node attributes as initial embeddings. Further, a neighborhood information aggregation (NIA) layer is designed for iteratively updating the embeddings of nodes by aggregating information from inter- and intra-domain neighbors in every view of the MVHN. Next, we combine embeddings of multiple NIA layers in each view, and integrate multiple views to obtain the final node embeddings, which are then fed into a discriminator to predict the existence of links. Extensive experiments show MVGCN performs better than or on par with baseline methods and has the generalization capacity on six benchmark datasets involving three typical tasks.

Availability and implementation

Source code and data can be downloaded from https://github.com/fuhaitao95/MVGCN.

Supplementary information

Supplementary data are available at Bioinformatics online.
Quantifying uncertainty in spikes estimated from calcium imaging data
Authors: Chen Yiqun T , Jewell Sean W , Witten Daniela M
Published: September 2021

In recent years, a number of methods have been proposed to estimate the times at which a neuron spikes on the basis of calcium imaging data. However, quantifying the uncertainty associated with these estimated spikes remains an open problem. We consider a simple and well-studied model for calcium imaging data, which states that calcium decays exponentially in the absence of a spike, and instantaneously increases when a spike occurs. We wish to test the null hypothesis that the neuron did not spike—i.e., that there was no increase in calcium—at a particular timepoint at which a spike was estimated. In this setting, classical hypothesis tests lead to inflated Type I error, because the spike was estimated on the same data used for testing. To overcome this problem, we propose a selective inference approach. We describe an efficient algorithm to compute finite-sample $p$-values that control selective Type I error, and confidence intervals with correct selective coverage, for spikes estimated using a recent proposal from the literature. We apply our proposal in simulation and on calcium imaging data from the $\texttt{spikefinder}$ challenge.
Building Public Confidence in Parole Boards: Findings From a Four-Country Study
Authors: Fitzgerald Robin , Freiberg Arie , Dodd Shannon , Bartels Lorana
Published: September 2021

Parole and parole boards play critical roles in criminal justice systems. With parolee numbers and imprisonment rates increasing in many countries, parole decision-making is a crucial contributor to prison population sizes and, more broadly, public confidence in the operation of correctional systems. This article examines the public understanding of and confidence in parole, from the perspectives of parole board members and other parole authority staff. It aims to determine whether and, if so, how, public opinion influences parole decision-making and how parole boards feel they can or should respond to this. It draws on interviews with 80 parole board members and other relevant staff in Australia, New Zealand, Canada and Scotland.
Improved robot-assisted laparoscopic telesurgery: feasibility of network converged communication
Authors: Chu G , Yang X , Luo L , Feng W , Jiao W , Zhang X , Wang Y , Yang Z , Wang B , Li J , Niu H
Published: September 2021

The converged transmission-assisted network communication architecture used in this study could meet the requirements of telesurgery, and effectively guarantee the security and immediacy of communication. With the security, flexibility, and universality of the network converged transmission, the clinical practical application of telesurgery and telemedicine would step up to a higher level.
St Gallen 2019 guidelines understage the axilla in lobular breast cancer: a population-based study
Authors: Narbe U , Bendahl P-O , Fernö M , Ingvar C , Dihge L , Rydén L
Published: September 2021

Background

The St Gallen 2019 guidelines for primary therapy of early breast cancer recommend omission of completion axillary lymph node dissection (cALND), regardless of histological type, in patients with one or two sentinel lymph node (SLN) metastases. Concurrently, adjuvant chemotherapy is endorsed for luminal A-like disease with four or more axillary lymph node (ALN) metastases. The aim of this study was to estimate the proportion of patients with invasive lobular cancer (ILC) versus invasive ductal cancer of no special type (NST) with one or two SLN metastases for whom cALND would have led to a recommendation for adjuvant chemotherapy.

Methods

Patients with ILC and NST who had surgery between 2014 and 2017 were identified in the National Breast Cancer Register of Sweden. After exclusion of patients with incongruent or missing data, those who fulfilled the St Gallen 2019 criteria for cALND omission were included in the population-based study cohort.

Results

Some 1886 patients in total were included in the study, 329 with ILC and 1507 with NST. Patients with ILC had a higher metastatic nodal burden and were more likely to have a luminal A-like subtype than those with NST. The prevalence of at least four ALN metastases was higher in ILC (31.0 per cent) than NST (14.9 per cent), corresponding to an adjusted odds ratio of 2.26 (95 per cent c.i. 1.59 to 3.21). Luminal A-like breast cancers with four or more ALN metastases were over-represented in ILC compared with NST, 52 of 281 (18.5 per cent) versus 43 of 1299 (3.3 per cent) (P < 0.001).

Conclusion

Patients with ILC more often have luminal A-like breast cancer with at least four nodal metastases. Omission of cALND in patients with luminal A-like invasive lobular cancer and one or two SLN metastases warrants future attention as there is a risk of nodal understaging and undertreatment in one-fifth of patients.
Effect of radiotherapy on expanders and permanent implants in immediate breast reconstruction: long-term surgical and patient-reported outcomes in a large multicentre cohort
Authors: Coudé Adam Hannah , Frisell Axel , Liu Yihang , Sackey Helena , Oikonomou Ira , Docherty Skogh Ann-Charlot , Frisell Jan , de Boniface Jana
Published: September 2021

Background

Current evidence for the effects of radiotherapy (RT) on implant-based immediate breast reconstruction (IBR) is limited by short follow-up and lack of patient-reported outcomes (PROs). It is central to integrate long-term comprehensive outcome data into the preoperative decision-making process. The aim of the present study was to determine long-term surgical outcomes and PROs in relation to RT after implant-based IBR.

Methods

This was a longitudinal cohort study of PRO data obtained in surveys conducted in 2012 and 2020 using the BREAST-Q questionnaire. All women undergoing therapeutic mastectomy and implant-based IBR between 1 January 2007 and 31 December 2011 at four breast centres in Stockholm, Sweden, were identified. The endpoint was implant removal owing to surgical complications or patient preference.

Results

Median follow-up was 120 (range 1–171) months. After 754 IBRs in 729 women, implant removal occurred in 128 (17 per cent): 34 of 386 (8.8 per cent) in the no-RT group, 20 of 64 (31.3 per cent) in the group with previous RT, and 74 of 304 (24.3 per cent) in the postoperative RT group (P < 0.001). Implant removal was because of surgical complications in 60 instances (7.9 per cent), and patient preference in 68 (9.0 per cent). The BREAST-Q response rate was 72.2 per cent. Women with previous RT scored lower than those without RT on all scales, apart from psychosocial well-being. Women with postoperative RT scored lower only on physical well-being. No scores in the two RT groups had deteriorated between the survey time points, whereas satisfaction with breasts and overall outcome had decreased in the no-RT group.

Conclusion

Although RT was significantly associated with higher implant removal rates, PROs remained stable over 8 years despite irradiation.
Nationwide registry study on trends in localization techniques and reoperation rates in non-palpable ductal carcinoma in situ and invasive breast cancer
Authors: Schermers Bram , van Riet Yvonne E , Schipper R J , Vrancken Peeters Marie-Jeanne , Voogd Adri C , Nieuwenhuijzen Grard A P , ten Haken Bennie , Ruers Theo J M
Published: September 2021

Background

There is a transition from wire-guided localization (WGL) of non-palpable breast cancer to other localization techniques. Multiple prospective studies have sought to establish superior clinical outcomes for radioactive-seed localization (RSL), but consistent and congruent evidence is missing.

Methods

In this study, female patients with breast cancer operated with breast-conserving surgery after tumour localization of a non-palpable breast cancer or ductal carcinoma in situ (DCIS) were included. The cohort was identified from the nationwide Netherlands Breast Cancer Audit conducted between 2013 and 2018. Trends in localization techniques were analysed. Univariable and multivariable analyses were performed to assess the association between the localization technique and the probability of a reoperation.

Results

A total of 28 370 patients were included in the study cohort. The use of RSL increased from 15.7 to 61.1 per cent during the study years, while WGL decreased from 75.4 to 31.6 per cent. The localization technique used (RSL versus WGL) was not significantly associated with the odds of a reoperation, regardless of whether the lesion was DCIS (odds ratio 0.96 (95 per cent c.i. 0.89 to 1.03; P = 0.281)) or invasive breast cancer (OR 1.02 (95 per cent c.i. 0.96 to 1.10; P = 0.518)).

Conclusion

RSL is rapidly replacing WGL as the preoperative localization technique in breast surgery. This large nationwide registry study found no association between the type of localization technique and the odds of having a reoperation, thus confirming the results of previous prospective cohort studies.
Repeat hepatic resection versus radiofrequency ablation for recurrent hepatocellular carcinoma: retrospective multicentre study
Authors: Zhong J -H , Xing B -C , Zhang W -G , Chan A W -H , Chong C C N , Serenari M , Peng N , Huang T , Lu S -D , Liang Z -Y , Huo R -R , Wang Y -Y , Cescon M , Liu T -Q , Li L , Wu F -X , Ma L , Ravaioli M , Neri J , Cucchetti A , Johnson P J , Li L -Q , Xiang B -D
Published: September 2021

Background

The therapeutic value of repeat hepatic resection (rHR) or radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma (HCC) is unknown. This study aimed to investigate the safety and efficacy of rHR or RFA.

Methods

This was a retrospective multicentre study of patients with recurrent HCC within the Milan criteria who underwent rHR or RFA at nine university hospitals in China and Italy between January 2003 and January 2018. Survival after rHR or RFA was examined in unadjusted analyses and after propensity score matching (1 : 1).

Results

Of 847 patients included, 307 and 540 underwent rHR and RFA respectively. Median overall survival was 73.5 and 67.0 months after rHR and RFA respectively (hazard ratio 1.01 (95 per cent c.i. 0.81 to 1.26)). Median recurrence-free survival was longer after rHR versus RFA (23.6 versus 15.2 months; hazard ratio 0.76 (95 per cent c.i. 0.65 to 0.89)). These results were confirmed after propensity score matching. RFA was associated with lower morbidity of grade 3 and above (0.6 versus 6.2 per cent; P < 0.001) and shorter hospital stay (8.0 versus 3.0 days, P < 0.001) than rHR.

Conclusion

rHR was associated with longer recurrence-free survival but not overall survival compared with RFA.
Cerebral microbleeds following thoracic endovascular aortic repair
Authors: Eilenberg Wolf , Bechstein Matthias , Charbonneau Philippe , Rohlffs Fiona , Eleshra Ahmed , Panuccio Giuseppe , Bhangu Jagdeep Singh , Fiehler Jens , Greenhalgh Rodger M , Haulon Stephan , Kölbel Tilo
Published: September 2021

Background

Stroke and neurological injury are a complication of thoracic endovascular aortic repair (TEVAR). Cerebral microbleeds (CMBs) are common in patients with white matter damage to the brain secondary to chronic vasculopathy. The aim of this study was to examine the occurrence of CMBs after TEVAR, and to evaluate their association with patient and procedural factors.

Methods

Patients who underwent TEVAR between September 2018 and January 2020 in two specialist European aortic centres were analysed. All patients underwent postoperative susceptibility-weighted MRI. The location and number of CMBs were identified, and analysed with regard to procedural aspects, clinical outcome, and Fazekas score as an indicator of pre-existing vascular leucoencephalopathy.

Results

Some 91 patients were included in the study. A total of 1531 CMBs were detected in 58 of 91 patients (64 per cent). In the majority of affected patients, CMBs were found bilaterally (79 per cent). Unilateral CMBs in the right or left hemisphere occurred in 16 and 5 per cent of patients respectively (P < 0.001). More CMBs were found in the middle cerebral than in the vertebrobasilar/posterior and anterior cerebral artery territories (mean(s.d.) 3.35(5.56) versus 2.26(4.05) versus 0.97(2.87); P = 0.045). Multivariable analysis showed an increased probability of CMBs after placement of TEVAR stent-grafts with a proximal diameter of at least 40 mm (odds ratio (OR) 6.85, 95 per cent c.i. 1.65 to 41.59; P = 0.007) and in patients with a higher Fazekas score on postoperative T2-weighted MRI (OR 2.62, 1.06 to 7.92; P = 0.037).

Conclusion

CMBs on postoperative MRI are common after endovascular repair in the aortic arch. Their occurrence appears to be associated with key aspects of the procedure and pre-existing vascular leucoencephalopathy.
Neoadjuvant immunotherapy in primary and metastatic colorectal cancer
Authors: Kanani A , Veen T , Søreide K
Published: September 2021

Background

Colorectal cancer (CRC) is the second most common solid organ cancer. Traditional treatment is with surgery and chemotherapy. Immunotherapy has recently emerged as a neoadjuvant therapy that could change treatment strategy in both primary resectable and metastatic CRC.

Methods

A literature review of PubMed with a focus on studies exploring upfront immunotherapy in operable CRC, either for primary resectable stage I–III cancers or for (potentially) operable liver metastasis.

Results

Immune checkpoint blockade by the programmed cell death 1 (PD-1) receptor inhibitors nivolumab and pembrolizumab and the cytotoxic T cell-associated protein 4 (CTLA-4) inhibitor ipilimumab has shown good results in both early-stage and advanced CRC. The effects of immune checkpoint inhibitors have so far been demonstrated in small phase I/II studies and predominantly in treatment-refractory stage IV disease with defect Mismatch repair (dMMR). However, recent data from phase I/II (NICHE-1) studies suggest an upfront role for immunotherapy in operable stage I–III disease. By blocking crucial immune checkpoints, cytotoxic T cells are activated and release cytotoxic signals that initiate cancer cell destruction. The very high complete response rate in dMMR operable CRC with neoadjuvant immunotherapy with nivolumab and ipilimumab, and even partial pathological response in some patients with proficient MMR (pMMR) CRC, calls for further attention to patient selection for neoadjuvant treatment, beyond MMR status alone.

Conclusion

Early data on the effect of immunotherapy in CRC provide new strategic thinking of treatment options in CRC for both early-stage and advanced disease, with prospects for new trials.
Venous wedge and segment resection during pancreatoduodenectomy for pancreatic cancer: impact on short- and long-term outcomes in a nationwide cohort analysis
Authors: Groen Jesse V , Michiels Nynke , van Roessel Stijn , Besselink Marc G , Bosscha Koop , Busch Olivier R , van Dam Ronald , van Eijck Casper H J , Koerkamp Bas Groot , van der Harst Erwin , de Hingh Ignace H , Karsten Tom M , Lips Daan J , de Meijer Vincent E , Molenaar Isaac Q , Nieuwenhuijs Vincent B , Roos Daphne , van Santvoort Hjalmar C , Wijsman Jan H , Wit Fennie , Zonderhuis Babs M , de Vos-Geelen Judith , Wasser Martin N , Bonsing Bert A , Stommel Martijn W J , Mieog J Sven D ,   for the Dutch Pancreatic Cancer Group
Published: September 2021

Background

Venous resection of the superior mesenteric or portal vein is increasingly performed in pancreatic cancer surgery, whereas results of studies on short- and long-term outcomes are contradictory. The aim of this study was to evaluate the impact of the type of venous resection in pancreatoduodenectomy for pancreatic cancer on postoperative morbidity and overall survival.

Methods

This nationwide retrospective cohort study included all patients who underwent pancreatoduodenectomy for pancreatic cancer in 18 centres (2013–2017).

Results

A total of 1311 patients were included, of whom 17 per cent underwent wedge resection and 10 per cent segmental resection. Patients with segmental resection had higher rates of major morbidity (39 versus 20 versus 23 per cent, respectively; P < 0.001) and portal or superior mesenteric vein thrombosis (18 versus 5 versus 1 per cent, respectively; P < 0.001) and worse overall survival (median 12 versus 16 versus 20 months, respectively; P < 0.001), compared to patients with wedge resection and those without venous resection. Multivariable analysis showed patients with segmental resection, but not those who had wedge resection, had higher rates of major morbidity (odds ratio = 1.93, 95 per cent c.i. 1.20 to 3.11) and worse overall survival (hazard ratio = 1.40, 95 per cent c.i. 1.10 to 1.78), compared to patients without venous resection. Among patients who received neoadjuvant therapy, there was no difference in overall survival among patients with segmental and wedge resection and those without venous resection (median 32 versus 25 versus 33 months, respectively; P = 0.470), although there was a difference in major morbidity rates (52 versus 19 versus 21 per cent, respectively; P  = 0.012).

Conclusion

In pancreatic surgery, the short- and long-term outcomes are worse in patients with venous segmental resection, compared to patients with wedge resection and those without venous resection.
Middle hepatic vein reconstruction in adult living donor liver transplantation: a randomized clinical trial
Authors: Durairaj Madhu Srinivasan , Shaji Mathew Johns , Mallick Shweta , Nair Krishnanunni , Manikandan K , Titus Varghese Christi , Chandran Biju , Amma Binoj Sivasankara Pillai Thankamony , Balakrishnan Dinesh , Gopalakrishnan Unnikrishnan , Menon Ramachandran Narayana , Vayoth Sudheer Othiyil , Surendran Sudhindran
Published: September 2021

Background

In adult right lobe living donor liver transplantation (LDLT), venous drainage of the anterior sector is usually reconstructed on the bench to form a neo-middle hepatic vein (MHV). Reconstruction of the MHV for drainage of the anterior sector is crucial for optimal graft function. The conduits used for reconstruction include cryopreserved allografts, synthetic grafts, or the recipient portal vein. However, the ideal choice remains a matter of debate. This study compares the efficacy of the native recipient portal vein (RPV) with PTFE grafts for reconstruction of the neo-MHV.

Methods

Patients in this equivalence-controlled, parallel-group trial were randomized to either RPV (62 patients) or PTFE (60 patients) for use in the reconstruction of the neo-MHV. Primary endpoint was neo-MHV patency at 14 days and 90 days. Secondary outcomes included 90-day mortality and post-transplant parameters as scored by predefined scoring systems.

Results

There was no statistically significant difference in the incidence of neo-MHV thrombosis at 14 days (RPV 6.5 per cent versus PTFE 10 per cent; P = 0.701) and 90 days (RPV 14.5 per cent versus PTFE 18.3 per cent; P = 0.745) between the two groups. Irrespective of the type of graft used for reconstruction, 90-day all-cause and sepsis-specific mortality was significantly higher among patients who developed neo-MHV thrombosis. Neo-MHV thrombosis and sepsis were identified as risk factors for mortality on Cox proportional hazards analysis. No harms or unintended side effects were observed in either group.

Conclusion

In adult LDLT using modified right lobe graft, use of either PTFE or RPV for neo-MHV reconstruction resulted in similar early patency rates. Irrespective of the type of conduit used for reconstruction, neo-MHV thrombosis is a significant risk factor for mortality.

Registration number

CTRI/2018/11/016315 (www.ctri.nic.in).
Centre volume impact on graft survival and waiting list time in donation after circulatory death liver transplantation in the USA
Authors: Giorgakis Emmanouil , Khorsandi Shirin E , Burdine Lyle , Singer Andrew , Hewitt Winston , Heaton Nigel , Mathur Amit K
Published: September 2021

During 2001–2015, numbers of donation after circulatory death (DCD) liver transplantations (LTs) remained surprisingly low. Post-transplant outcomes improved overall over time, regardless of centre volume. High-volume centres that promoted DCD LT significantly shortened their waiting list time, therefore limiting waiting list mortality and drop-outs.
Theorising Social Work Sense-Making: Developing a Model of Peer-Aided Judgement and Decision Making
Authors: Helm Duncan
Published: September 2021

This article addresses the challenges of sense making in social work practice and presents a descriptive model of peer-aided judgement to facilitate critical debate and knowledge creation. The model is founded in Hammond's Cognitive Continuum Theory and developed in direct application to social work practice. It seeks to expand currently available models of social work judgement and decision making to include processes and outcomes related to informal peer interaction. Building on empirical studies and multiple contemporary literatures, a model of peer-aided judgement is hypothesised, comprising four distinct and interacting elements. By modelling these fundamental aspects of the processes and outcomes of peer-aided judgement, this article provides a tool for illuminating the everyday unseen value of peer interaction in practice and a framework for critical debate of dilemmas and propositions for professional judgement in social work practice. This article concludes by examining some of the implications of the model and its potential use in the further development of theory, methodology and practice.
Treatment strategies for mosaic overgrowth syndromes of the PI3K-AKT-mTOR pathway
Authors: Morin Gabriel , Canaud Guillaume
Published: September 2021

Introduction or background

Mosaic overgrowth syndromes (OS) are a proteiform ensemble of rare diseases displaying asymmetric overgrowth involving any tissue type, with degrees of severity ranging from isolated malformation to life-threatening conditions such as pulmonary embolism. Despite discordant clinical presentations, all those syndromes share common genetic anomalies: somatic mutations of genes involved in cell growth and proliferation. The PI3K-AKT-mTOR signaling pathway is one of the most prominent regulators of cell homeostasis, and somatic oncogenic mutations affecting this pathway are responsible for mosaic OS. This review aims to describe the clinical and molecular characteristics of the main OS involving the PI3K-AKT-mTOR pathway, along with the treatments available or under development.

Sources of data

This review summarizes available data regarding OS in scientific articles published in peer-reviewed journals.

Areas of agreement

OS care requires a multidisciplinary approach relying on clinical and radiological follow-up along with symptomatic treatment. However, no specific treatment has yet shown efficacy in randomized control trials.

Areas of controversy

Clinical classifications of OS led to frequent misdiagnosis. Moreover, targeted therapies directed at causal mutated proteins are developing in OSs through cancer drugs repositioning, but the evidence of efficacy and tolerance is still lacking for most of them.

Growing points

The genetic landscape of OS is constantly widening and molecular classifications tend to increase the accuracy of diagnosis, opening opportunities for targeted therapies.

Areas timely for developing research

OS are a dynamic, expanding field of research. Studies focusing on the identification of genetic anomalies and their pharmacological inhibition are needed.
Predictors of functional outcomes in patients with facioscapulohumeral muscular dystrophy
Authors: Katz Natalie K , Hogan John , Delbango Ryan , Cernik Colin , Tawil Rabi , Statland Jeffrey M
Published: September 2021

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most prevalent muscular dystrophies characterized by considerable variability in severity, rates of progression and functional outcomes. Few studies follow FSHD cohorts long enough to understand predictors of disease progression and functional outcomes, creating gaps in our understanding, which impacts clinical care and the design of clinical trials. Efforts to identify molecularly targeted therapies create a need to better understand disease characteristics with predictive value to help refine clinical trial strategies and understand trial outcomes.

Here we analysed a prospective cohort from a large, longitudinally followed registry of patients with FSHD in the USA to determine predictors of outcomes such as need for wheelchair use. This study analysed de-identified data from 578 individuals with confirmed FSHD type 1 enrolled in the United States National Registry for FSHD Patients and Family members. Data were collected from January 2002 to September 2019 and included an average of 9 years (range 0–18) of follow-up surveys. Data were analysed using descriptive epidemiological techniques, and risk of wheelchair use was determined using Cox proportional hazards models. Supervised machine learning analysis was completed using Random Forest modelling and included all 189 unique features collected from registry questionnaires. A separate medications-only model was created that included 359 unique medications reported by participants.

Here we show that smaller allele sizes were predictive of earlier age at onset, diagnosis and likelihood of wheelchair use. Additionally, we show that females were more likely overall to progress to wheelchair use and at a faster rate as compared to males, independent of genetics. Use of machine learning models that included all reported clinical features showed that the effect of allele size on progression to wheelchair use is small compared to disease duration, which may be important to consider in trial design. Medical comorbidities and medication use add to the risk for need for wheelchair dependence, raising the possibility for better medical management impacting outcomes in FSHD.

The findings in this study will require further validation in additional, larger datasets but could have implications for clinical care, and inclusion criteria for future clinical trials in FSHD.
Sensory processing dysregulations as reliable translational biomarkers in SYNGAP1 haploinsufficiency
Authors: Carreño-Muñoz Maria Isabel , Chattopadhyaya Bidisha , Agbogba Kristian , Côté Valérie , Wang Siyan , Lévesque Maxime , Avoli Massimo , Michaud Jacques L , Lippé Sarah , Di Cristo Graziella
Published: September 2021

Amongst the numerous genes associated with intellectual disability, SYNGAP1 stands out for its frequency and penetrance of loss-of-function variants found in patients, as well as the wide range of co-morbid disorders associated with its mutation. Most studies exploring the pathophysiological alterations caused by Syngap1 haploinsufficiency in mouse models have focused on cognitive problems and epilepsy; however, whether and to what extent sensory perception and processing are altered by Syngap1 haploinsufficiency is less clear. By performing EEG recordings in awake mice, we identified specific alterations in multiple aspects of auditory and visual processing, including increased baseline gamma oscillation power, increased theta/gamma phase amplitude coupling following stimulus presentation and abnormal neural entrainment in response to different sensory modality-specific frequencies. We also report lack of habituation to repetitive auditory stimuli and abnormal deviant sound detection. Interestingly, we found that most of these alterations are present in human patients as well, thus making them strong candidates as translational biomarkers of sensory-processing alterations associated with SYNGAP1/Syngap1 haploinsufficiency.
Empowering women through the Self-Help Group Bank Linkage Programme as a tool for sustainable development: lessons from India
Authors: Al-Kubati Nada Amer Abdulhafedh , Selvaratnam Doris Padmini
Published: September 2021

The purpose of this study is to look at India’s experience in using the Self-Help Group Bank Linkage Programme as a core development strategy aimed to empower women. Self-help groups are seen as socially active groups that can facilitate a government’s plans towards achieving the sustainable development goals. Today, the Self-Help Group Bank Linkage Programme is the largest microfinance programme globally, covering more than 10 million self-help groups. This article uses descriptive analysis to provide an overview of India’s experience. It focuses on how the program contributes to sustainable development by asking how the Self-Help Group Bank Linkage Programme leads to the empowerment of rural women, the challenges faced in its implementation, and the initiatives implemented in India to sustain the programme. This is followed by a quantitative analysis of the economic sustainability and the equality status by measuring the programme’s progress and the disparity between regions in the last decade. India’s experience shows that the Self-Help Group Bank Linkage Programme can empower women, facilitate entrepreneurial activities, enhance confidence and trust, provide technical skills and market access. Those are part of sustainable development goals and increase sustainable livelihood.
Top-down processes derail bottom-up objectives: a study in community engagement and ‘Slum-Free City Planning’
Authors: Sanga Naganika , Gonzalez Benson Odessa , Josyula Lakshmi
Published: September 2021

Participatory processes in housing policies and planning that engage urban poor communities through grassroots networks have been widely celebrated, but scholars have also scrutinized these policies for their limitations on the ground. Such scholarship has primarily focused on outcome indicators and local implementation, relegating the state to the background. This study focuses on everyday practices rather than outcomes and on multi-level rather than local-level implementation, using India’s national Slum-Free City Planning initiative, Rajiv Awas Yojana, in the mid-sized, southern city of Madurai as a case study. This paper draws from development studies literature to ‘bring the state back in’ to critically examine participatory planning with India’s urban poor. Findings illustrate how community participation ideals are sacrificed by different players for procedural expediency and bureaucratic convenience. We suggest that the deprioritizing of community participation is not an isolated deviation from policy, but it is shaped by two structural impediments embedded within urban housing policy mechanisms: the lack of federal constitutional mandates for housing and, in their absence, the proliferation of time-bound and project-based conditional grants through national housing programmes for the urban poor. Together, they result in an arbitrary policy environment and a push-pull of power between different levels of government, thereby sidelining community participation objectives.
Aging-Related Differences in Structural and Functional Interhemispheric Connectivity
Authors: Lewis John D , O’Reilly Christian , Bock Elizabeth , Theilmann Rebecca J , Townsend Jeanne
Published: September 2021

There is substantial evidence of age-related declines in anatomical connectivity during adulthood, with associated alterations in functional connectivity. But the relation of those functional alterations to the structural reductions is unclear. The complexities of both the structural and the functional connectomes make it difficult to determine such relationships. We pursue this question with methods, based on animal research, that specifically target the interhemispheric connections between the visual cortices. We collect t1- and diffusion-weighted imaging data from which we assess the integrity of the white matter interconnecting the bilateral visual cortices. Functional connectivity between the visual cortices is measured with electroencephalography during the presentation of drifting sinusoidal gratings that agree or conflict across hemifields. Our results show age-related reductions in the integrity of the white matter interconnecting the visual cortices, and age-related increases in the difference in functional interhemispheric lagged coherence between agreeing versus disagreeing visual stimuli. We show that integrity of the white matter in the splenium of the corpus callosum predicts the differences in lagged coherence for the agreeing versus disagreeing stimuli; and that this relationship is mediated by age. These results give new insight into the causal relationship between age and functional connectivity.
A Multivariate Functional Connectivity Approach to Mapping Brain Networks and Imputing Neural Activity in Mice
Authors: Brier Lindsey M , Zhang Xiaohui , Bice Annie R , Gaines Seana H , Landsness Eric C , Lee Jin-Moo , Anastasio Mark A , Culver Joseph P
Published: September 2021

Temporal correlation analysis of spontaneous brain activity (e.g., Pearson “functional connectivity,” FC) has provided insights into the functional organization of the human brain. However, bivariate analysis techniques such as this are often susceptible to confounding physiological processes (e.g., sleep, Mayer-waves, breathing, motion), which makes it difficult to accurately map connectivity in health and disease as these physiological processes affect FC. In contrast, a multivariate approach to imputing individual neural networks from spontaneous neuroimaging data could be influential to our conceptual understanding of FC and provide performance advantages. Therefore, we analyzed neural calcium imaging data from Thy1-GCaMP6f mice while either awake, asleep, anesthetized, during low and high bouts of motion, or before and after photothrombotic stroke. A linear support vector regression approach was used to determine the optimal weights for integrating the signals from the remaining pixels to accurately predict neural activity in a region of interest (ROI). The resultant weight maps for each ROI were interpreted as multivariate functional connectivity (MFC), resembled anatomical connectivity, and demonstrated a sparser set of strong focused positive connections than traditional FC. While global variations in data have large effects on standard correlation FC analysis, the MFC mapping methods were mostly impervious. Lastly, MFC analysis provided a more powerful connectivity deficit detection following stroke compared to traditional FC.
Novel Gyrification Networks Reveal Links with Psychiatric Risk Factors in Early Illness
Authors: Sanfelici Rachele , Ruef Anne , Antonucci Linda A , Penzel Nora , Sotiras Aristeidis , Dong Mark Sen , Urquijo-Castro Maria , Wenzel Julian , Kambeitz-Ilankovic Lana , Hettwer Meike D , Ruhrmann Stephan , Chisholm Katharine , Riecher-Rössler Anita , Falkai Peter , Pantelis Christos , Salokangas Raimo K R , Lencer Rebekka , Bertolino Alessandro , Kambeitz Joseph , Meisenzahl Eva , Borgwardt Stefan , Brambilla Paolo , Wood Stephen J , Upthegrove Rachel , Schultze-Lutter Frauke , Koutsouleris Nikolaos , Dwyer Dominic B ,   the PRONIA Consortium
Published: September 2021

Adult gyrification provides a window into coordinated early neurodevelopment when disruptions predispose individuals to psychiatric illness. We hypothesized that the echoes of such disruptions should be observed within structural gyrification networks in early psychiatric illness that would demonstrate associations with developmentally relevant variables rather than specific psychiatric symptoms. We employed a new data-driven method (Orthogonal Projective Non-Negative Matrix Factorization) to delineate novel gyrification-based networks of structural covariance in 308 healthy controls. Gyrification within the networks was then compared to 713 patients with recent onset psychosis or depression, and at clinical high-risk. Associations with diagnosis, symptoms, cognition, and functioning were investigated using linear models. Results demonstrated 18 novel gyrification networks in controls as verified by internal and external validation. Gyrification was reduced in patients in temporal-insular, lateral occipital, and lateral fronto-parietal networks (pFDR < 0.01) and was not moderated by illness group. Higher gyrification was associated with better cognitive performance and lifetime role functioning, but not with symptoms. The findings demonstrated that gyrification can be parsed into novel brain networks that highlight generalized illness effects linked to developmental vulnerability. When combined, our study widens the window into the etiology of psychiatric risk and its expression in adulthood.
Network Diffusion Embedding Reveals Transdiagnostic Subnetwork Disruption and Potential Treatment Targets in Internalizing Psychopathologies
Authors: Thomas Paul J , Leow Alex , Klumpp Heide , Phan K Luan , Ajilore Olusola
Published: September 2021

Network diffusion models are a common and powerful way to study the propagation of information through a complex system and they offer straightforward approaches for studying multimodal brain network data. We developed an analytic framework to identify brain subnetworks with perturbed information diffusion capacity using the structural basis that best maps to resting state functional connectivity and applied it towards a heterogeneous dataset of internalizing psychopathologies (IPs), a set of psychiatric conditions in which similar brain network deficits are found across the swath of the disorders, but a unifying neuropathological substrate for transdiagnostic symptom expression is currently unknown. This research provides preliminary evidence of a transdiagnostic brain subnetwork deficit characterized by information diffusion impairment of the right area 8BM, a key brain region involved in organizing a broad spectrum of cognitive tasks, which may underlie previously reported dysfunction of multiple brain circuits in the IPs. We also demonstrate that models of neuromodulation involving targeting this brain region normalize IP diffusion dynamics towards those of healthy controls. These analyses provide a framework for multimodal methods that identify both brain subnetworks with disrupted information diffusion and potential targets of these subnetworks for therapeutic neuromodulatory intervention based on previously well-characterized methodology.
Reduced Hippocampal-Striatal Interactions during Formation of Durable Episodic Memories in Aging
Authors: Ness Hedda T , Folvik Line , Sneve Markus H , Vidal-Piñeiro Didac , Raud Liisa , Geier Oliver M , Nyberg Lars , Walhovd Kristine B , Fjell Anders M
Published: September 2021

Encoding of durable episodic memories requires cross-talk between the hippocampus and multiple brain regions. Changes in these hippocampal interactions could contribute to age-related declines in the ability to form memories that can be retrieved after extended time intervals. Here we tested whether hippocampal–neocortical– and subcortical functional connectivity (FC) observed during encoding of durable episodic memories differed between younger and older adults. About 48 younger (20–38 years; 25 females) and 43 older (60–80 years; 25 females) adults were scanned with fMRI while performing an associative memory encoding task. Source memory was tested ~20 min and ~6 days postencoding. Associations recalled after 20 min but later forgotten were classified as transient, whereas memories retained after long delays were classified as durable. Results demonstrated that older adults showed a reduced ability to form durable memories and reduced hippocampal–caudate FC during encoding of durable memories. There was also a positive relationship between hippocampal–caudate FC and higher memory performance among the older adults. No reliable age group differences in durable memory–encoding activity or hippocampal–neocortical connectivity were observed. These results support the classic theory of striatal alterations as one cause of cognitive decline in aging and highlight that age-related changes in episodic memory extend beyond hippocampal–neocortical connections.