bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel approaches in uterus transplantation
Authors: Brännström Mats , Kvarnström Niclas , Dahm-Kähler Pernilla 
Published: October 2020

Purpose of review
Uterus transplantation (UTx) is the first existing infertility treatment for women with no uterus and for women with a present nonfunctional uterus, which is unable to carry a pregnancy. This type of transplantation is a novel addition within the field of vascularized composite allografts and is the first ephemeral kind of transplantation, with the graft intended for only a restricted number of years, until the desired numbers of children have been born and with subsequent graft removal. The proof-of-concept of UTx, as an infertility treatment for women with uterine factor infertility, came with the report of the first live birth after UTx, occurring in Sweden in 2014. This UTx live birth has been followed by around 30 births, taking place in four continents. Despite the initial clinical success, UTx should still be regarded as an experimental procedure, at a developmental phase. The clinical UTx activities at several centers around the globe take place within scientific clinical trials and aim to advance UTx further. This review describes certain developmental areas around UTx. These relate to surgery, donor selection, assisted reproduction, and inclusion of new recipient groups.

Recent findings
Successful UTx procedures, with live births, have been reported both after live and deceased donor transplantation. There exist developments in the areas of robotic surgery for live donor hysterectomy, of alternate vascular connections to the graft, modifications of inclusion criteria/investigations of donors, assisted reproduction in conjunction with UTx, as well as discussions concerning expanding the pool of eligible recipients.

Summary
Uterus transplantation has repeatedly proven to be a feasible infertility treatment for women with absolute uterine factor infertility. Ongoing studies aim to increase safety and efficiency of the procedure as well as to better define suitable donors and recipients.
Novel Approach of Mandibular Distraction to Avoid Tracheostomy in KAT6B-related Gene Disorders
Authors: Bacos Jonathan , Maduekwe Uma , Janes Lindsay , Gosain Arun K. 
Published: October 2020

Abstract
Previously, severe upper airway obstruction in patients with retrognathia and glossoptosis has been managed with tracheostomy. However, tracheostomy is associated with significant morbidity. In recent years, mandibular distraction has become an alternative management strategy in infants, but these applications have been limited to patient populations with retrognathia and glossoptosis. The authors present 2 unique cases of patients with KAT6B-related gene disorders, who present with a paradox of tongue-based airway obstruction in the absence of retrognathia. In both cases mandibular distraction osteogenesis with an obliquely oriented vector was successfully performed and both children avoided the need for tracheostomy.
Tailoring Research Recruitment for Acute Care Settings
Authors: Friz Amanda M. , Benson Clark , Mullen Shannon , Block Laura , Gilmore-Bykovskyi Andrea 
Published: October 2020

Background:
There is a pressing need to increase enrollment and representation in Alzheimer’s disease and related dementia (ADRD) research. Current recruitment approaches focus largely on clinic and community settings, with minimal engagement of acute care environments despite their broad use across diverse populations. The objectives of this study were to examine views, preferences, and recommendations regarding acute care–based ADRD research recruitment among persons with dementia and their caregivers.

Methods:
The authors conducted semistructured interviews with recently hospitalized persons with dementia (N=3) and family caregivers (N=28). Interviews were analyzed using thematic analysis.

Findings:
All participants endorsed acute care as an appropriate time for recruitment into ADRD research studies and identified important elements of an appropriately tailored recruitment approach and an interpersonally effective research staff. Participants emphasized that this approach should consider the acute care context with respect to participant situation, uncertainty, and timing. Participant suggestions informed the design of a 5-step process to guide ADRD research recruitment in the context of acute care.

Discussion:
Findings provide valuable insights from people with dementia and their caregivers regarding opportunities for research engagement surrounding acute care and can inform expanded recruitment in these settings.
Uncovering biomarkers during therapeutic neuromodulation with PARRM: Period-based Artifact Reconstruction and Removal Method
Authors: Dastin-van Rijn Evan M. , Provenza Nicole R. , Calvert Jonathan S. , Gilron Ro’ee , Allawala Anusha B. , Darie Radu , Syed Sohail , Matteson Evan , Vogt Gregory S. , Avendano-Ortega Michelle , Vasquez Ana C. , Ramakrishnan Nithya , Oswalt Denise N. , Bijanki Kelly R. , Wilt Robert , Starr Philip A. , Sheth Sameer A. , Goodman Wayne K. , Harrison Matthew T. , Borton David A. 
Published: October 2020

AbstractAdvances in device development have enabled concurrent stimulation and recording at adjacent locations in the central nervous system. However, stimulation artifacts obscure the sensed underlying neural activity. Here, we developed a novel method, termed Period-based Artifact Reconstruction and Removal Method (PARRM), to remove stimulation artifacts from neural recordings by leveraging the exact period of stimulation to construct and subtract a high-fidelity template of the artifact. Benchtop saline experiments, computational simulations, five uniquein vivoparadigms across animal and human studies, and an obscured movement biomarker were used for validation. Performance was found to exceed that of state-of-the-art filters in recovering complex signals without introducing contamination. PARRM has several advantages: it is 1) superior in signal recovery; 2) easily adaptable to several neurostimulation paradigms; and 3) low-complexity for future on-device implementation. Real-time artifact removal via PARRM will enable unbiased exploration and detection of neural biomarkers to enhance efficacy of closed-loop therapies.SummaryOnline, real-time artifact removal via PARRM will enable unbiased exploration of neural biomarkers previously obscured by stimulation artifact.
The Power of Social Information in Ant-Colony House-Hunting: A Computational Modeling Approach
Authors: Zhao Jiajia , Lynch Nancy , Pratt Stephen C. 
Published: October 2020

AbstractThe decentralized cognition of animal groups is both a challenging biological problem and a potential basis for bio-inspired design. The understanding of these systems and their application can benefit from modeling and analysis of the underlying algorithms. In this study, we define a modeling framework that can be used to formally represent all components of such algorithms. As an example application of the framework, we adapt to it the much-studied house-hunting algorithm used by emigrating colonies ofTemnothoraxants to reach consensus on a new nest. We provide a Python simulator that encodes accurate individual behavior rules and produces simulated behaviors consistent with empirical observations, on both the individual and group levels. Critically, through multiple simulated experiments, our results highlight the value of individual sensitivity to site population in ensuring consensus. With the help of this social information, our model successfully reproduces experimental results showing the high cognitive capacity of colonies and their rational time investment during decision-making, and also predicts the pros and cons of social information with regard to the colonies’ ability to avoid and repair splits. Additionally, we use the model to make new predictions about several unstudied aspects of emigration behavior. Our results indicate a more complex relationship between individual behavior and the speed/accuracy trade-off than previously appreciated. The model proved relatively weak at resolving colony divisions among multiple sites, suggesting either limits to the ants’ ability to reach consensus, or an aspect of their behavior not captured in our model. It is our hope that these insights and predictions can inspire further research from both the biology and computer science community.
Human USP18 is regulated by miRNAsviathe 3’UTR, a sequence duplicated in lincRNA genes residing in chr22q11.21
Authors: Rubino Erminia , Cruciani Melania , Tchitchek Nicolas , Le Tortorec Anna , Rolland Antoine D. , Veli Önay , Vallet Leslie , Gaggi Giulia , Michel Frédérique , Dejucq-Rainsford Nathalie , Pellegrini Sandra 
Published: October 2020

ABSTRACTUbiquitin-specific peptidase 18 (USP18) acts as gatekeeper of type I interferon (IFN) responses by binding to the IFN receptor subunit IFNAR2 and preventing activation of the downstream JAK/STAT pathway. In any given cell type, the level of USP18 is a key determinant of the output of interferon-stimulated transcripts. How the baseline level of USP18 is finely tuned in different cell types remains ill defined. Here we explored post-transcriptional regulation of USP18 by microRNAs (miRNAs) and identified four miRNAs (miR-24-3p, miR-191-5p, miR-423-5pandmiR-532-3p) that efficiently targetUSP18through binding to the 3’UTR. Among these, three miRNAs are particularly enriched in circulating monocytes which exhibit low baselineUSP18. Intriguingly, theUSP183’UTR sequence is duplicated in human and chimpanzee genomes. In human, we found several copies of the 3’UTR that are embedded in long intergenic non-coding (linc) RNA genes residing in chr22q11.21 and exhibiting a tissue-specific expression pattern. Interestingly, one of these lincRNAs (here namedlinc-UR-B1) is uniquely and highly expressed in testis. RNA-seq data analyses from testicular cell subsets revealed a positive correlation betweenlinc-UR-B1andUSP18expression in spermatocytes and spermatids. Overall, our findings uncover a set of miRNAs and lincRNAs, which may be part of a network evolved to fine-tune baseline USP18, particularly in cell types where IFN responsiveness needs to be tightly controlled.SIGNIFICANT STATEMENTUSP18 is a non-redundant negative feedback regulator of type I IFN signaling and a key determinant of cell responsiveness to IFN. How baseline USP18 is set in different human cell types is ill defined. We identified three microRNAs that restrain USP18 level notably in primary monocytes through binding the 3’UTR. We found several copies of the USP18 3’UTR embedded in long intergenic non-coding (linc) RNAs which reside in a complex region of human chromosome 22. These lincRNAs are expressed in a tissue-specific manner. We describe one lincRNA expressed only in testis, and most notably in germ cells. Correlative analyses suggest that microRNAs and lincRNAs may form a network controlling baseline USP18 and IFN responsiveness.
The Poisson-lognormal model as a versatile framework for the joint analysis of species abundances
Authors: Chiquet Julien , Mariadassou Mahendra , Robin Stéphane 
Published: October 2020

AbstractJoint Species Abundance Models (JSDM) provide a general multivariate framework to study the joint abundances of all species from a community. JSDM account for both structuring factors (environmental characteristics or gradients, such as habitat type or nutrient availability) and potential interactions between the species (competition, mutualism, parasitism, etc.), which is instrumental in disentangling meaningful ecological interactions from mere statistical associations.Modeling the dependency between the species is challenging because of the count-valued nature of abundance data and most JSDM rely on Gaussian latent layer to encode the dependencies between species in a covariance matrix. The multivariate Poisson-lognormal (PLN) model is one such model, which can be viewed as a multivariate mixed Poisson regression model. The inference of such models raises both statistical and computational issues, many of which were solved in recent contributions using variational techniques and convex optimization.The PLN model turns out to be a versatile framework, within which a variety of analyses can be performed, including multivariate sample comparison, clustering of sites or samples, dimension reduction (ordination) for visualization purposes, or inference of interaction networks. This paper presents the general PLN framework and illustrates its use on a series a typical experimental datasets. All the models and methods are implemented in theRpackagePLNmodels, available fromcran.r-project.org.
Mild traumatic brain injury induces transient, sequential increases in proliferation, neuroblasts/immature neurons, and cell survival: a time course study in the male mouse dentate gyrus
Authors: Clark LR , Yun S , Acquah NK , Kumar PL , Metheny HE , Paixao RCC , Cohen AS , Eisch AJ 
Published: October 2020

AbstractMild traumatic brain injuries (mTBIs) are prevalent worldwide. mTBIs can impair hippocampal-based functions such as memory and cause network hyperexcitability of the dentate gyrus (DG), a key entry point to hippocampal circuitry. One candidate for mediating mTBI-induced hippocampal cognitive and physiological dysfunction is injury-induced changes in the process of DG neurogenesis. There are conflicting results on how TBI impacts the process of DG neurogenesis; this is not surprising given that both the neurogenesis process and the post-injury period are dynamic, and that the quantification of neurogenesis varies widely in the literature. Even within the minority of TBI studies focusing specifically on mild injuries, there is disagreement about if and how mTBI changes the process of DG neurogenesis. Here we utilized a clinically-relevant rodent model of mTBI (lateral fluid percussion injury, LFPI), gold-standard markers and quantification of the neurogenesis process, and three time points post-injury to generate a comprehensive picture of how mTBI affects adult hippocampal DG neurogenesis. Male C57BL/6J mice (6-8 weeks old) received either sham surgery or mTBI via LFPI. Proliferating cells, neuroblasts/immature neurons, and surviving cells were quantified via stereology in DG subregions (subgranular zone [SGZ], outer granule cell layer [oGCL], molecular layer, and hilus) at short-term (3 days post-injury, dpi), intermediate (7 dpi), and long-term (31 dpi) time points. The data suggest this model of mTBI induces transient, sequential increases in ipsilateral SGZ/GCL proliferating cells, neuroblasts/immature neurons, and surviving cells which are suggestive of mTBI-induced neurogenesis. In contrast to these ipsilateral hemisphere findings, measures in the contralateral hemisphere were not increased in key neurogenic DG subregions after LFPI. Our work in this mTBI model is in line with most literature on other and more severe models of TBI in showing TBI stimulates the process of DG neurogenesis. However, as our DG data in mTBI provide temporal, subregional, and neurogenesis-stage resolution, these data are important to consider in regard to the functional importance of TBI-induction of the neurogenesis process and future work assessing the potential of replacing and/or repairing DG neurons in the brain after TBI.
Robust switches in thalamic network activity require a timescale separation between sodium and T-type calcium channel activations
Authors: Jacquerie Kathleen , Drion Guillaume 
Published: October 2020

AbstractSwitches in brain states, synaptic plasticity and neuromodulation are fundamental processes in our brain that take place concomitantly across several spatial and timescales. All these processes target neuron intrinsic properties and connectivity to achieve specific physiological goals, raising the question of how they can operate without interfering with each other. Here, we highlight the central importance of a timescale separation in the activation of sodium and T-type calcium channels to sustain robust switches in brain states in thalamic neurons that are compatible with synaptic plasticity and neuromodulation. We quantify the role of this timescale separation by comparing the robustness of rhythms of six published conductance-based models at the cellular, circuit and network levels. We show that robust rhythm generation requires a T-type calcium channel activation whose kinetics are situated between sodium channel activation and T-type calcium channel inactivation in all models despite their quantitative differences.
TREM2 alters the phagocytic, apoptotic and inflammatory response to Aβ42in HMC3 cells
Authors: Akhter Rumana , Shao Yvonne , Formica Shane , Khrestian Maria , Bekris Lynn M. 
Published: October 2020

AbstractAlzheimer’s disease (AD) is characterized by the accumulation in the brain of extracellular amyloid β (Aβ) plaques as well as intraneuronal inclusions (neurofibrillary tangles) consisting of total tau and phosphorylated tau. Also present are dystrophic neurites, loss of synapses, neuronal death, and gliosis. AD genetic studies have highlighted the importance of inflammation in this disease by identifying several risk associated immune response genes, including TREM2. TREM2 has been strongly implicated in basic microglia function including, phagocytosis, apoptosis, and the inflammatory response to Aβ in mouse brain and primary cells. These studies show that microglia are key players in the response to Aβ and in the accumulation of AD pathology. However, details are still missing about which apoptotic or inflammatory factors rely on TREM2 in their response to Aβ, especially in human cell lines. Given these previous findings our hypothesis is that TREM2 influences the response to Aβ toxicity by enhancing phagocytosis and inhibiting both the BCL-2 family of apoptotic proteins and pro-inflammatory cytokines. Aβ42treatment of the human microglial cell line, HMC3 cells, was performed and TREM2 was overexpressed or silenced and the phagocytosis, apoptosis and inflammatory response were evaluated. Results indicate that a robust phagocytic response to Aβ after 24 hours requires TREM2 in HMC3 cells. Also, TREM2 inhibits Aβ induced apoptosis by activating the Mcl-1/Bim complex. TREM2 is involved in activation of IP-10, MIP-1a, and IL-8, while it inhibits FGF-2, VEGF and GRO. Taken together, TREM2 plays a role in enhancing the microglial functional response to Aβ toxicity in HMC3 cells. This novel information suggests that therapeutic strategies that seek to activate TREM2 may not only enhance phagocytosis, but it may also inhibit beneficial inflammatory factors, emphasizing the need to define TREM2-related inflammatory activity in not only mouse models of AD, but also in human AD.
Atypical molecular basis for drug resistance to mitochondrial function inhibitors inPlasmodium falciparum
Authors: Painter Heather J. , Morrisey Joanne M. , Mather Michael W. , Orchard Lindsey M. , Luck Cuyler , Smilkstein Martin J. , Riscoe Michael K. , Vaidya Akhil B. , Llinás Manuel 
Published: October 2020

AbstractThe continued emergence of drug-resistantPlasmodium falciparumparasites hinders global attempts to eradicate malaria, emphasizing the need to identify new antimalarial drugs. Attractive targets for chemotherapeutic intervention are the cytochrome (cyt)bc1complex, which is an essential component of the mitochondrial electron transport chain (mtETC) necessary for ubiquinone recycling and mitochondrially localized dihydroorotate dehydrogenase (DHODH) critical forde novopyrimidine synthesis. Despite the essentiality of this complex, resistance to a novel acridone class of compounds targeting cytbc1was readily attained, resulting in a parasite strain (SB1-A6) that was pan-resistant to both mtETC and DHODH inhibitors. Here we describe the molecular mechanism behind the resistance of the SB1-A6 parasite line which lacks the common cytbc1point mutations characteristic of resistance to mtETC inhibitors. Using Illumina whole-genome sequencing, we have identified both a copy number variation (∼2x) and a single-nucleotide polymorphism (C276F) associated withpfdhodhin SB1-A6. We have characterized the role of both genetic lesions by mimicking the copy number variation via episomal expression ofpfdhodhand introducing the identified SNP using CRISPR/Cas9 and assessed their contributions to drug resistance. Although both of these genetic polymorphisms have been previously identified as contributing to both DSM-1 (1) and atovaquone resistance (2, 3), SB1-A6 represents a unique genotype in which both alterations are present in a single line, suggesting that the combination contributes to the pan-resistant phenotype. This novel mechanism of resistance to mtETC inhibition has critical implications for the development of future drugs targeting thebc1complex orde novopyrimidine synthesis that could help guide future anti-malarial combination therapies and reduce the rapid development of drug resistance in the field.
Attractive internuclear force drives the collective behavior of nuclear arrays inDrosophilaembryos
Authors: Wu Xiaoxuan , Kong Kakit , Xiao Wenlei , Liu Feng 
Published: October 2020

ABSTRACTThe emerging collective behaviors during embryogenesis play an important role in precise and reproducible morphogenesis. An important question in the study of collective behavior is what rule underlies the emerging pattern. Here we use theDrosophilaembryo as a test tube to study this question. We focus on the nuclear array without membrane separation on the embryo periphery from the nuclear cycle (NC) 11 to NC14. After live imaging with light sheet microscopy, we extract the nuclear trajectory, speed, and internuclear distance with an automatic nuclear tracing method. We find that the nuclear speed shows a period of standing waves along the anterior-posterior (AP) axis after each metaphase as the nuclei collectively migrate towards the embryo poles and partially move back. And the maximum nuclear speed dampens by 38% in the second half of the standing wave. Moreover, the nuclear density is 35% higher in the middle than the pole region of the embryo during the S phase of NC11-NC14. To find mechanical rules controlling the collective motion and packing patterns of the nuclear array, we use the deep neural network (DNN) to learn the force field from data. We find two potential strong nuclear-age-dependent force fields, i.e., the repulsive or attractive force field. Simulations with the particle-based model indicate that only if the net internuclear force is attractive and increases with distance, the pseudo-synchronous mitotic wave in a nuclear array with lower nuclear density in embryo poles can drive the collective motion with the damped standing wave of the nuclear speed, and the collective nuclear motion, in turn, maintains the non-uniform nuclear density.