bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pediatric kidney transplantation, a technical update
Authors: Etesami Kambiz , Hogen Rachel , Lestz Rachel 
Published: June 2021

Purpose of review
Pediatric kidney transplantation is the definitive therapy for infants and children suffering from renal failure. It is a distinct endeavor demanding specialized care for optimal results. This includes a dedicated preoperative workup accounting for unique predisposing urologic conditions, specialized surgical techniques, and careful hemodynamic monitoring and maintenance.

Recent findings
Historically, size-matched renal allografts from pediatric donors to pediatric recipients suffered from poor outcomes. Advances in surgical technique performed at high volume centers have shown that these operations can be performed safely, helping expand the donor pool for these patients. Concurrently, transplantation of increasingly small for size infants with complex medical and surgical backgrounds has become a reality.

Summary
On a policy front, efforts to expand access to size-matched organs, combined with advances in medical management and immunosuppression have seen pediatric renal transplantation reach new heights. Now, these breakthroughs are heightened by the ability to transplant such organs into the smallest infants. The net result will be diminished transplant waiting times and, accordingly, improved quality of life and longevity for children suffering from renal failure.
Expanding access to pancreas transplantation for type 2 diabetes mellitus
Authors: Papageorge Christina M. , Bolognese Alexandra C. , Odorico Jon S. 
Published: June 2021

Purpose of review
The vast majority of cases of diabetes mellitus (DM) in the United States are classified as type 2 DM (T2DM). Restrictive listing criteria and uncertainty regarding outcomes have historically limited access to pancreas transplantation for individuals with T2DM, although it has been used with success in patients with type 1 DM (T1DM). This review summarizes several recent studies that have sought to clarify the indications, appropriate patient selection, and outcomes of pancreas transplantation in the setting of T2DM.

Recent findings
Pancreas transplants have increased over the last few years, largely due to an increase in listings for simultaneous pancreas-kidney transplant (SPK) in patients with T2DM. Retrospective data demonstrate similar patient and allograft survival in patients with T1DM and T2DM undergoing SPK, and improved outcomes in patients with T2DM after SPK compared to those receiving a kidney transplant alone, although these studies are often confounded by selection biases. Patient selection for pancreas transplant has traditionally focused on body mass index, pretransplant insulin requirements, and fasting C-peptide, and the categorization of patients to T1DM or T2DM. Emerging data suggests this practice is inadvertently and unnecessarily restrictive.

Summary
There is a growing body of evidence to support increasing consideration of pancreas transplantation in patients with T2DM, with support for equivalent patient and graft survival and glycemic control. Future prospective studies are indicated to better evaluate the role of preoperative patient factors in selection for pancreas transplantation and to explore long-term outcomes in patients with T2DM.
Analgesic effect of central relaxin receptor activation on persistent inflammatory pain in mice: behavioral and neurochemical data
Authors: Abboud Cynthia , Brochoire Louison , Drouet Adèle , Hossain M. Akhter , Hleihel Walid , Gundlach Andrew L. , Landry Marc 
Published: June 2021

Abstract

Introduction:
The relaxin peptide signaling system is involved in diverse physiological processes, but its possible roles in the brain, including nociception, are largely unexplored.

Objective:
In light of abundant expression of relaxin receptor (RXFP1) mRNA/protein in brain regions involved in pain processing, we investigated the effects of central RXFP1 activation on nociceptive behavior in a mouse model of inflammatory pain and examined the neurochemical phenotype and connectivity of relaxin and RXFP1 mRNA-positive neurons.

Methods:
Mice were injected with Complete Freund Adjuvant (CFA) into a hind paw. After 4 days, the RXFP1 agonist peptides, H2-relaxin or B7-33, ± the RXFP1 antagonist, B-R13/17K-H2, were injected into the lateral cerebral ventricle, and mechanical and thermal sensitivity were assessed at 30 to 120 minutes. Relaxin and RXFP1 mRNA in excitatory and inhibitory neurons were examined using multiplex, fluorescent in situ hybridization. Relaxin-containing neurons were detected using immunohistochemistry and their projections assessed using fluorogold retrograde tract-tracing.

Results:
Both H2-relaxin and B7-33 produced a strong, but transient, reduction in mechanical and thermal sensitivity of the CFA-injected hind paw alone, at 30 minutes postinjection. Notably, coinjection of B-R13/17K-H2 blocked mechanical, but not thermal, analgesia. In the claustrum, cingulate cortex, and subiculum, RXFP1 mRNA was expressed in excitatory neurons. Relaxin immunoreactivity was detected in neurons in forebrain and midbrain areas involved in pain processing and sending projections to the RXFP1-rich, claustrum and cingulate cortex. No changes were detected in CFA mice.

Conclusion:
Our study identified a previously unexplored peptidergic system that can control pain processing in the brain and produce analgesia.
A computational framework for crack propagation in spatially heterogeneous materials
Authors: Lewandowski Karol , Kaczmarczyk Łukasz , Athanasiadis Ignatios , Marshall John F. , Pearce Chris J. 
Published: June 2021

This paper presents a mathematical formulation and numerical modelling framework for brittle crack propagation in heterogeneous elastic solids. Such materials are present in both natural and engineered scenarios. The formulation is developed in the framework of configurational mechanics and solved numerically using the finite-element method. We show the methodology previously established for homogeneous materials without the need for any further assumptions. The proposed model is based on the assumption of maximal dissipation of energy and uses the Griffith criterion; we show that this is sufficient to predict crack propagation in brittle heterogeneous materials, with spatially varying Young’s modulus and fracture energy. Furthermore, we show that the crack path trajectory orientates itself such that it is always subject to Mode-I. The configurational forces and fracture energy release rate are both expressed exclusively in terms of nodal quantities, avoiding the need for post-processing and enabling a fully implicit formulation for modelling the evolving crack front and creation of new crack surfaces. The proposed formulation is verified and validated by comparing numerical results with both analytical solutions and experimental results. Both the predicted crack path and load–displacement response show very good agreement with experiments where the crack path was independent of material heterogeneity for those cases. Finally, the model is successfully used to consider the real and challenging scenario of fracture of an equine bone, with spatially varying material properties obtained from CT scanning.This article is part of a discussion meeting issue ‘A cracking approach to inventing new tough materials: fracture stranger than friction’.
Common and rare variant analyses combined with single-cell multiomics reveal cell-type-specific molecular mechanisms of COVID-19 severity
Authors: Zhang Sai , Cooper-Knock Johnathan , Weimer Annika K. , Harvey Calum , Julian Thomas H. , Wang Cheng , Li Jingjing , Furini Simone , Frullanti Elisa , Fava Francesca , Renieri Alessandra , Pan Cuiping , Song Jina , Billing-Ross Paul , Gao Peng , Shen Xiaotao , Timpanaro Ilia Sarah , Kenna Kevin P. ,   VA Million Veteran Program,   GEN-COVID Network, Davis Mark M. , Tsao Philip S. , Snyder Michael P. 
Published: June 2021

ABSTRACTThe determinants of severe COVID-19 in non-elderly adults are poorly understood, which limits opportunities for early intervention and treatment. Here we present novel machine learning frameworks for identifying common and rare disease-associated genetic variation, which outperform conventional approaches. By integrating single-cell multiomics profiling of human lungs to link genetic signals to cell-type-specific functions, we have discovered and validated over 1,000 risk genes underlying severe COVID-19 across 19 cell types. Identified risk genes are overexpressed in healthy lungs but relatively downregulated in severely diseased lungs. Genetic risk for severe COVID-19, within both common and rare variants, is particularly enriched in natural killer (NK) cells, which places these immune cells upstream in the pathogenesis of severe disease. Mendelian randomization indicates that failed NKG2D-mediated activation of NK cells leads to critical illness. Network analysis further links multiple pathways associated with NK cell activation, including type-I-interferon-mediated signalling, to severe COVID-19. Our rare variant model, PULSE, enables sensitive prediction of severe disease in non-elderly patients based on whole-exome sequencing; individualized predictions are accurate independent of age and sex, and are consistent across multiple populations and cohorts. Risk stratification based on exome sequencing has the potential to facilitate post-exposure prophylaxis in at-risk individuals, potentially based around augmentation of NK cell function. Overall, our study characterizes a comprehensive genetic landscape of COVID-19 severity and provides novel insights into the molecular mechanisms of severe disease, leading to new therapeutic targets and sensitive detection of at-risk individuals.
Paternal body mass index before conception associated with offspring’s birth weight in Chinese population: a prospective study
Authors: Xu Renying , Zhao Weixiu , Tan Tao , Li Haojie , Wan Yanping 
Published: June 2021

AbstractWhether paternal epigenetic information of nutrition might be inherited by their offspring remained unknown. evaluate the relationship between preconception paternal body weight and their offspring’s birth weight in 1,810 Chinese mother-father-baby trios. Information on paternal and maternal preconception body weight and height was collected via a self-reported questionnaire. Birth weight was collected from medical records. Paternal preconception body weight was associated with offspring’s birth weight (p trend=0.02) after multivariable adjustment. Each standard deviation increment of paternal body mass index was associated with an additional 29.6 g increase of birth weight (95% confident interval: 5.7g, 53.5g). The association was more pronounced in male neonates, and neonates with overweight mothers, and with mothers who gained excessive gestational weight, compared to their counterparts (all p interaction<0.05). Sensitivity analyses showed similar pattern to that of the main analysis. Paternal preconception body weight was associated with birth weight of their offspring.Impact statementWhat is already known on this subject?More efforts have previously been put on the maternal contribution to birth weight, however, it is uncertain whether paternal pre-conceptional body weight, an indicator for epigenetic information, might be inherited by their offspring.What do the results of this study add?In the current study that included 1,810 Chinese mother-father-baby trios, a small but significant association was observed between paternal preconception body weight and offspring’s birth weight (p trend=0.02).What are the implications of these findings for clinical practice and/or further research?Paternal epigenetic information of nutrition could be inherited by their offspring.
Micro-RNAs miR-375-3p and miR-7-5p are released alongside ACTH from corticotroph pituitary neuroendocrine tumor
Authors: Niedra Helvijs , Peculis Raitis , Konrade Ilze , Balcere Inga , Romanovs Mihails , Steina Liva , Stukens Janis , Sokolovska Jelizaveta , Klovins Janis , Rovite Vita 
Published: June 2021

AbstractObjectiveCirculating miRNAs are found in bodily fluids including plasma and can serve as biomarkers for diseases. The aim of this study was to provide the first insight into the landscape of circulating miRNAs in close proximity to the adrenocorticotropic hormone (ACTH) secreting PitNET. To achieve this objective next-generation sequencing of miRNAs in plasma from bilateral inferior petrosal sinus sampling (BIPSS) - a gold standard in diagnosing ACTH-secreting PitNETs, was carried out.MethodsSinistral (left) and dextral (right) BIPSS blood samples of the patient were collected in three time points: before the administration of corticotropin-releasing hormone, 5 and 15 minutes after stimulation. Peripheral venous blood samples were also collected 24 hours before and after BIPSS and before the resection of PitNET and 24 hours after. In differential expression analysis sinistral plasma was compared with dextral.ResultsBIPSS concluded that the highest amount of ACTH was released in the sinistral side at the 5th minute mark indicating a presence of tumor. The highest amount of differentially expressed miRNAs was observed 5 minutes after stimulation (20 upregulated, 14 downregulated). At the 5th minute mark in sinistral plasma, two miRNAs were identified: hsa-miR-7-5p and hsa-miR-375-3p that were highly upregulated compared to other BIPSS samples and peripheral plasma samples. Clustering analysis showed that BIPSS plasma differs from peripheral plasma in miRNA expression patterns.Conclusionsdata indicates that ACTH-secreting PitNET actively releases two circulating miRNAs upon stimulation with CRH (hsa-mir-7-5p, hsa-mir-375-3p) alongside with ACTH implying further studies of these miRNA as diagnostic markers are needed.
Role of physiotherapy team in critically ill COVID-19 patients pronation: can a multidisciplinary management reduce the complications rate?
Authors: Glotta Andrea , Faldarini Nicola , Biggiogero Maira , Saporito Andrea , Olivieri Diana , Molteni Claudia , Petazzi Stefano , Mauri Romano , Capdevila Xavier , Ceruti Samuele 
Published: June 2021

ABSTRACTObjectivesDuring the pandemic, critically ill COVID-19 patients’ management presented an increased workload for Intensive Care Unit (ICU) nursing staff, particularly during pronation maneuvers, with high risk of complications. In this scenario, a support during pronation by theICU Physiotherapy Teamwas introduced.Research methodologyRetrospective analysis. Consecutive critically ill COVID-19 patients.SettingA COVID-19 Center in southern Switzerland, between March 16thand April 30th, 2020.Main Outcome MeasuresRates and characteristics of pronation-related complications.ResultsForty-two patients on mechanical ventilation (MV) were treated; 296 standard prone/supine positioning were performed, with 3.52 cycles/patient. One (0.3%) major complication was observed, while fourteen (33.3%) patients developed minor complications, e.g. pressure injuries. The incidence of pressure sores was related to ICU length-of-stay (LOS) (p = 0.029) and MV days (p = 0.015), while their number (n = 27) further correlated with ICU LOS (p = 0.001) and MV days (p = 0.001). The propensity matching score analysis did not show any protective factor of pronation regarding pressure injuries (p = 0.448). No other significant correlation was found.ConclusionThe specific pronation team determined a low rate of major complications in critically ill COVID19 patients. The high rate of minor complications appeared to be related to disease severity, rather than from pronation.
Diverse tumorigenic consequences of human papillomavirus integration in primary oropharyngeal cancers
Authors: Symer David E. , Akagi Keiko , Geiger Heather M. , Song Yang , Li Gaiyun , Emde Anne-Katrin , Xiao Weihong , Jiang Bo , Li Jingfeng , Agrawal Amit D. , Ozer Enver , Naggar Adel El , Du Zoe , Shewale Jitesh , Stache-Crain Birgit , Zucker Mark , Robine Nicolas , Coombes Kevin R. , Gillison Maura L. 
Published: June 2021

SUMMARYHuman papillomavirus (HPV) causes 5% of all cancers and frequently integrates into host chromosomes, but the impacts of integration in tumorigenesis remain unclear. Analysis of 105 HPV-positive oropharyngeal cancers by whole genome sequencing detects viral integration in 77%, revealing five statistically significant integration hotspots near genes that regulate epithelial stem cell maintenance (i.e. SOX2, TP63, FGFR, MYC) and immune evasion (i.e. CD274). Somatic hyperamplification is enriched 16-fold near HPV integrants, and the extent of focal host genomic instability increases with local density of HPV integrants. Genes expressed at extreme outlier levels are increased 86-fold within +/- 150 kb of integrants. Across 95% of tumors with integration, host gene transcription is disrupted via intragenic integrants, chimeric transcription, outlier expression, gene breaking and/or de novo expression of noncoding or imprinted genes. We conclude that HPV integration contributes substantively to cancer development by causing extensive disruption of host genome structure and gene expression.
A hemifused complex is the hub in a network of pathways to membrane fusion
Authors: Warner Jason M. , An Dong , Stratton Benjamin S. , O’Shaughnessy Ben 
Published: June 2021

AbstractMembrane fusion is a critical step for many essential processes, from neurotransmission to fertilization. For over 40 years protein-free fusion driven by calcium or other cationic species has provided a simplified model of biological fusion, but the mechanisms remain poorly understood. Cation-mediated membrane fusion and permeation are essential in their own right to drug delivery strategies based on cell-penetrating peptides or cation-bearing lipid nanoparticles. Experimental studies suggest calcium drives anionic membranes to a hemifused intermediate which constitutes a hub in a network of pathways, but the pathway selection mechanism is unknown. Here we develop a mathematical model that identifies the network hub as a highly dynamical hemifusion complex. Multivalent cations drive expansion of this high tension hemifusion interface between interacting vesicles during a brief transient. The fate of this interface determines the outcome, either fusion, dead-end hemifusion or vesicle lysis. The model reproduces the unexplained finding that calcium-driven fusion of vesicles with planar membranes typically stalls at hemifusion, and we show the equilibrated hemifused state is a novel lens-shaped complex. Thus, membrane fusion kinetics follow a stochastic trajectory within a network of pathways, with outcome weightings set by a hemifused complex intermediate.SignificanceCells use multicomponent machineries to fuse membranes for neurotransmitter and hormone release and other fundamental processes. Protein-free fusion using calcium or other multivalent cationic fusogens has long been studied as a simplifying model. Cation-mediated membrane fusion or permeation are key events for a number of current drug delivery strategies. However, the mechanisms determining outcomes are unknown. Here we develop a mathematical model that identifies a dynamic hemifusion complex as the decision hub that stochastically sets the outcome in a network of pathways. Cations transiently grow a high tension hemifusion interface between membrane-enclosed compartments, whose fate governs whether fusion, dead-end hemifusion or vesicle lysis occurs. The model provides a systematic framework to predict outcomes of cationic fusogen-mediated interactions between membrane-enclosed compartments.
A genotype independent DMP-HI system in dicot crops
Authors: Zhong Yu , Chen Baojian , Wang Dong , Zhu Xijian , Wang Yuwen , Li Mengran , Li Yifan , Liu Jinchu , Zhang Jinzhe , Chen Ming , Wang Min , Riksen Tjitske , Qi Xiaolong , Cheng Dehe , Liu Zongkai , Li Jinlong , Chen Chen , Jiao Yanyan , Liu Wenxin , Yi Bin , Huang Sanwen , Liu Chenxu , Boutilier Kim , Chen Shaojiang 
Published: June 2021

ABSTRACTDoubled haploid (DH) technology is used to obtain homozygous lines in a single generation, which significantly accelerates the crop breeding trajectory. Traditionally, in vitro culture is used to generate DHs, but is limited by species and genotype recalcitrance. In vivo haploid induction (HI) through seed is been widely and efficiently used in maize and was recently extended to several monocot crops. However, a similar generic and efficient HI system is still lacking in dicot crops. Here we show that genotype-independent in vivo HI can be triggered by mutation of DMP genes in tomato, rapeseed and tobacco with HI rates of ~1.9%, 2.4% and 1.2%, respectively. The DMP-HI system offers a robust DH technology to facilitate variety improvement in these crops. The success of this approach and the conservation of DMP genes paves the way for a generic and efficient genotype-independent HI system in other dicot crops.
Deposition chamber technology as building blocks for a standardized brain-on-chip framework
Authors: Maisonneuve B. G. C. , Libralesso L. , Miny L. , Batut A. , Rontard J. , Gleyzes M. , Boudra B. , Viera J. , Debis D. , Larramendy F. , Jost V. , Honegger T. 
Published: June 2021

AbstractIn vitro modeling of human brain connectomes is key to explore the structure-function relationship of the central nervous system. The comprehension of this intricate relationship will serve to better study the pathological mechanisms of neurodegeneration, and hence to perform improved drug screenings for complex neurological disorders, such as Alzheimer’s and Parkinson’s diseases. However, currently used in vitro modeling technologies lack potential to mimic physiologically relevant neural structures, because they are unable to represent the concurrent interconnectivity between myriad subtypes of neurons across multiple brain regions. Here, we present an innovative microfluidic design that allows the controlled and uniform deposition of various specialized neuronal populations within unique plating chambers of variable size and shape. By applying our design, we offer novel neuro-engineered microfluidic platforms, so called neurofluidic devices, which can be strategically used as organ-on-a-chip platforms for neuroscience research. Through the fine tuning of the hydrodynamic resistance and the cell deposition rate, the number of neurons seeded in each plating chamber can be tailored from a thousand up to a million, creating multi-nodal circuits that represent connectomes existing within the intact brain. These advances provide essential enhancements to in vitro platforms in the quest accurately model the brain for the investigation of human neurodegenerative diseases.