bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant immunotherapy in primary and metastatic colorectal cancer
Authors: Kanani A , Veen T , Søreide K 
Published: September 2021

Abstract

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

Abstract

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 &lt; 0.001) and portal or superior mesenteric vein thrombosis (18 versus 5 versus 1 per cent, respectively; P &lt; 0.001) and worse overall survival (median 12 versus 16 versus 20 months, respectively; P &lt; 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

Abstract

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).
Theorising Social Work Sense-Making: Developing a Model of Peer-Aided Judgement and Decision Making
Authors: Helm Duncan 
Published: September 2021

AbstractThis 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

Abstract

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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractThere 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

Abstract
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

Abstract
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 &lt; 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.