bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mini- or Less-open Sublay Operation (MILOS): A New Minimally Invasive Technique for the Extraperitoneal Mesh Repair of Incisional Hernias
Authors: Reinpold Wolfgang , Schröder Michael , Berger Cigdem , Nehls Jennifer , Schröder Alexander , Hukauf Martin , Köckerling Ferdinand , Bittner Reinhard 
Published: January 2018

Objective:
Improvement of ventral hernia repair.

Background:
Despite the use of mesh and other recent improvements, the currently popular techniques of ventral hernia repair have specific disadvantages and risks.

Methods:
We developed the endoscopically assisted mini- or less-open sublay (MILOS) concept. The operation is performed transhernially via a small incision with light-holding laparoscopic instruments either under direct, or endoscopic visualization. An endoscopic light tube was developed to facilitate this approach (EndotorchTM Wolf Company). Each MILOS operation can be converted to standard total extraperitoneal gas endoscopy once an extraperitoneal space of at least 8 cm has been created. All MILOS operations were prospectively documented in the German Hernia registry with 1 year questionnaire follow-up. Propensity score matching of incisional hernia operations comparing the results of the MILOS operation with the laparoscopic intraperitoneal onlay mesh operation (IPOM) and open sublay repair from other German Hernia registry institutions was performed.

Results:
Six hundred fifteen MILOS incisional hernia operations were included. Compared with laparoscopic IPOM incisional hernia operation, the MILOS repair is associated with significantly a fewer postoperative surgical complications (P < 0.001) general complications (P < 0.004), recurrences (P < 0.001), and less chronic pain (P < 0.001). Matched pair analysis with open sublay repair revealed significantly a fewer postoperative complications (P < 0.001), reoperations (P < 0.001), infections (P = 0.007), general complications (P < 0.001), recurrences (P = 0.017), and less chronic pain (P < 0.001).

Conclusions:
The MILOS technique allows minimally invasive transhernial repair of incisional hernias using large retromuscular/preperitoneal meshes with low morbidity. The technique combines the advantages of open sublay and the laparoscopic IPOM repair.
ClinicalTrials.gov Identifier NCT03133000
Retinal Arterio-Arterial Collaterals in Susac Syndrome
Authors: Egan Robert A. , Jirawuthiworavong Guy , Lincoff Norah S. , Chen John J. , Francis Courtney E. , Leavitt Jacqueline A. 
Published: January 2018

Background:
The ophthalmic findings of Susac syndrome (SS) consist of visual field defects related to branch retinal artery occlusion (BRAO), and fluorescein angiography (FA) reveals a unique staining pattern. To date, retinal arterial collateral development has been described only in a single patient. Given that the immunopathological process in SS induces retinal ischemia, it is conceivable that abnormal blood vessel development may occur in affected individuals.

Methods:
This is a retrospective observational study. The medical records including fundus photography and FA of all patients with SS were reviewed, and those with any type of retinal arterial collateral were identified.

Results:
A total of 11 patients were identified with retinal collaterals. Five were men. Age ranged from 20 to 50 years. Ten patients had arterio-arterial (A-A) collaterals and 1 had arterio-venous (A-V) collaterals, and all had collaterals remote from the optic disc. No collaterals were present at onset of illness and the first developed at 9 months.

Conclusions:
The literature reveals scant evidence for the association between BRAO and retinal arterial collaterals. Our findings indicate that retinal arterial collaterals in SS are usually A-A and not A-V and may be more common in this disorder than previously believed. Collaterals do not develop early in the disease, and there may be a predilection toward development in men. The chronic inflammatory state of SS may be the stimulus for the development of these arterial collaterals.
Single-cell transcriptome analysis reveals estrogen signaling augments the mitochondrial folate pathway to coordinately fuel purine and polyamine synthesis in breast cancer cells
Authors: Zhu Detu , Zhaozu Xianglan , Cui Guimei , Chang Shiehong , See Yi Xiang , Lim Michelle Gek Liang , Guo Dajiang , Chen Xin , Robson Paul , Luo Yumei , Cheung Edwin 
Published: January 2018

AbstractEstrogen regulates diverse physiological effects and drives breast tumor progression by directly activating estrogen receptor α (ERα). However, due to the stochastic nature of gene transcription and the resulting heterogeneous cellular response, it is important to investigate estrogen-stimulated gene expression profiles at the single-cell level in order to fully understand how ERα regulates transcription in breast cancer cells. In this study, we performed single-cell transcriptome analysis on ERα-positive breast cancer cell lines following 17β-estradiol stimulation. Overall, we observed robust gene expression diversity between individual cells. Moreover, we found over two thirds of the genes in breast cancer cells displayed a bimodal expression pattern, which caused averaging artifacts and masked the identification of potential estrogen-regulated genes. We overcame this issue by reconstructing a dynamic estrogen-responsive transcriptional network from discrete time points into a pseudotemporal continuum. Pathway analysis of the differentially expressed genes derived from the pseudotemporal analysis showed an estrogen-stimulated metabolic switch that favored biosynthesis and cell proliferation but reduced estrogen degradation. In addition, we identified folate-mediated one-carbon metabolism as a novel estrogen-regulated pathway in breast cancer cells. Notably, estrogen stimulation reprogramed this pathway through the mitochondrial folate pathway to coordinately fuel polyamine and de novo purine synthesis. Finally, we showed AZIN1 and PPAT, key regulators in the above pathways, are direct ERα target genes and essential for breast cancer cell survival and growth. In summary, our single-cell study illustrated a dynamic transcriptional heterogeneity in ERα-positive breast cancer cells in response to estrogen stimulation and uncovered a novel mechanism of an estrogen-mediated metabolic switch.
The Viral Protein Corona Directs Viral Pathogenesis and Amyloid Aggregation
Authors: Ezzat Kariem , Pernemalm Maria , Pålsson Sandra , Roberts Thomas C. , Järver Peter , Dondalska Aleksandra , Bestas Burcu , Sobkowiak Michal J. , Levänen Bettina , Sköld Magnus , Thompson Elizabeth A. , Saher Osama , Kari Otto K. , Lajunen Tatu , Ekström Eva Sverremark , Nilsson Caroline , Ishchenko Yevheniia , Malm Tarja , Wood Matthew J.A. , Power Ultan F. , Masich Sergej , Lindén Anders , Sandberg Johan K. , Lehtiö Janne , Spetz Anna-Lena , Andaloussi Samir EL 
Published: January 2018

AbstractArtificial nanoparticles accumulate a protein corona layer in biological fluids, which significantly influences their bioactivity. As nanosized obligate intracellular parasites, viruses share many biophysical properties with artificial nanoparticles in extracellular environments and here we show that respiratory syncytial virus (RSV) and herpes simplex virus 1 (HSV-1) accumulate a rich and distinctive protein corona in different biological fluids. Moreover, we show that corona pre-coating differentially affects viral infectivity and immune cell activation. Additionally, we demonstrate that viruses bind amyloidogenic peptides in their corona and catalyze amyloid formation via surface-assisted heterogeneous nucleation. Importantly, we show that HSV-1 catalyzes the aggregation of the amyloid beta peptide (Aβ42), a major constituent of amyloid plaques in Alzheimer’s disease, in-vitro and in animal models. Our results highlight the viral protein corona as an acquired structural layer that is critical for viral-host interactions and illustrate a mechanistic convergence between viral and amyloid pathologies.
Using Network Analysis to Localize the Epileptogenic Zone from Invasive EEG Recordings in Intractable Focal Epilepsy
Authors: Li Adam , Chennuri Bhaskar , Subramanian Sandya , Yaffe Robert , Gliske Steve , Stacey William , Norton Robert , Jordan Austin , Zaghloul Kareem A. , Inati Sara K. , Agrawal Shubhi , Haagensen Jennifer J. , Hopp Jennifer , Atallah Chalita , Johnson Emily , Crone Nathan , Anderson William S. , Fitzgerald Zach , Bulacio Juan , Gale John T. , Sarma Sridevi V. , Gonzalez-Martinez Jorge 
Published: January 2018

AbstractTreatment of medically intractable focal epilepsy (MIFE) by surgical resection of the epileptogenic zone (EZ) is often effective provided the EZ can be reliably identified. Even with the use of invasive recordings, the clinical differentiation between the EZ and normal brain areas can be quite challenging, mainly in patients without MRI detectable lesions. Consequently, despite relatively large brain regions being removed, surgical success rates barely reach 60-65%. Such variable and unfavorable outcomes associated with high morbidity rates are often caused by imprecise and/or inaccurate EZ localization. We developed a localization algorithm that uses network-based data analytics to process invasive EEG recordings. This network algorithm analyzes the centrality signatures of every contact electrode within the recording network and characterizes contacts into susceptible EZ based on the centrality trends over time. The algorithm was tested in a retrospective study that included 42 patients from four epilepsy centers. Our algorithm had higher agreement with EZ regions identified by clinicians for patients with successful surgical outcomes and less agreement for patients with failed outcomes. These findings suggest that network analytics and a network systems perspective of epilepsy may be useful in assisting clinicians in more accurately localizing the EZ.AUTHOR SUMMARYEpilepsy is a disease that results in abnormal firing patterns in parts of the brain that comprise the epileptogenic network, known as the epileptogenic zone (EZ). Current methods to localize the EZ for surgical treatment often requires observations of hundreds of thousands of EEG data points measured from many electrodes implanted in a patient’s brain. In this paper, we used network science to show that EZ regions may exhibit specific network signatures before, during and after seizure events. Our algorithm computes the likelihood of each electrode being in the EZ and tends to agree more with clinicians during successful resections and less during failed surgeries. These results suggest that a networked analysis approach to EZ localization may be valuable in a clinical setting.
Efficient computation of co-transcriptional RNA-ligand interaction dynamics
Authors: Wolfinger Michael T. , Flamm Christoph , Hofaeker Ivo L. 
Published: January 2018

AbstractRiboswitches form an abundant class of cis-regulatory RNA elements that mediate gene expression by binding a small metabolite. For synthetic biology applications, they are becoming cheap and accessible systems for selectively triggering transcription or translation of downstream genes. Many riboswitches are kinetically controlled, hence knowledge of their co-transcriptional mechanisms is essential. We present here an efficient implementation for analyzing co-transcriptional RNA-ligand interaction dynamics. This approach allows for the first time to model concentration-dependent metabolite binding/unbinding kinetics. We exemplify this novel approach by means of the recently studied I-A 2’-deoxyguanosine (2’dG)-sensing riboswitch from Mesoplasma florum.
A genomic region containingREC8andRNF212Bis associated with individual recombination rate variation in a wild population of red deer (Cervus elaphus)
Authors: Johnston Susan E. , Huisman Jisca , Pemberton Josephine M. 
Published: January 2018

AbstractRecombination is a fundamental feature of sexual reproduction, ensuring proper disjunction, preventing mutation accumulation and generating new allelic combinations upon which selection can act. However it is also mutagenic, and breaks up favourable allelic combinations previously built up by selection. Identifying the genetic drivers of recombination rate variation is a key step in understanding the causes and consequences of this variation, how lociassociated with recombination are evolving and how they affect the potential of a population to respond to selection. However, to date, few studies have examined the genetic architecture of recombination rate variation in natural populations. Here, we use pedigree data from ‐2,600 individuals genotyped at ‐38,000 SNPs to investigate the genetic architecture of individual autosomal recombination rate in a wild population of red deer (Cervus elaphus). Female red deer exhibited a higher mean and phenotypic variance in autosomal crossover counts (ACC). Animal models fitting genomic relatedness matrices showed that ACC was heritable in females (h2= 0.12) but not in males. A regional heritability mapping approach showed that almost all heritable variation in female ACC was explained by a genomic region on deer linkage group 12 containing the candidate lociREC8andRNF212B, with an additional region on linkage group 32 containingTOP2Bapproaching genome-wide significance. TheREC8/RNF212Bregion and its paralogueRNF212have been associated with recombination in cattle, mice, humans and sheep. Our findings suggest that mammalian recombination rates have a relatively conserved genetic architecture in both domesticated and wild systems, and provide a foundation for understanding the association between recombination lociand individual fitness within this population.
Estradiol treatment in a nonhuman primate model of menopause preserves affective reactivity
Authors: Bliss-Moreau Eliza , Baxter Mark G. 
Published: January 2018

AbstractAs humans age, their affective lives tend to become more positive and less negative. This phenomenon, known as the positivity effect (or positivity bias), occurs even as aging leads to declines in health and cognitive outcomes. Despite these well documented effects in humans, extent to which affective processes change in nonhuman animals, and in particular nonhuman primates – is unclear. As a first step towards developing a model for human affective aging in rhesus monkeys (Macaca mulatta), we tested aged, surgically menopausal aged and middle-aged gonadally intact female rhesus monkeys on a classic index of affective reactivity in monkeys, the Human Intruder task. The Human Intruder task evaluates behavioral responses to varying levels of threat. Aged, surgically menopausal monkeys received hormone replacement therapy consisting of a cyclic estradiol regimen, or vehicle injections as a control. Average responsivity to threat did not vary by condition, but middle aged monkeys and aged monkeys on estradiol were more reactive to the most potent level of threat than to a moderate level of threat, replicating previously published results in other age groups and male monkeys. In contrast, aged monkeys not on estradiol did not show such calibration to threat level. These findings suggest that estrogen may be important for maintaining more youthful affective responding. They also illustrate the utility of behavioral assays of affective reactivity in nonhuman primate models of cognitive and reproductive aging in humans.
Zebrabase: An intuitive tracking solution for aquatic model organisms
Authors: Oltova Jana , Jindrich Jindrich , Skuta Ctibor , Svoboda Ondrej , Machonova Olga , Bartunek Petr 
Published: January 2018

AbstractSmall fish species, like zebrafish or medaka, are constantly gaining popularity in basic research and disease modeling as a useful alternative to rodent model organisms. However, the tracking options for fish within a facility are rather limited. Here, we present an aquatic species tracking database, Zebrabase, developed in our zebrafish research and breeding facility that represents a practical and scalable solution and an intuitive platform for scientists, fish managers and caretakers, in both small and large facilities. Zebrabase is a scalable, crossplatform fish tracking database developed especially for research fish facilities but can be easily adapted for a wide variety of aquatic model organisms housed in tanks. It provides sophisticated tracking, reporting, and management functions that help keep the animalrelated records well-organized including a QR code functionality for tank labeling. The implementation of various user roles ensures a functional hierarchy and customized access to specific functions and data. In addition, Zebrabase enables easy personalization of rooms and racks, and its advanced statistics and reporting options make it an excellent tool for creating periodic reports of animal usage and productivity. The communication between the facility and researchers can be streamlined by the requesting capabilities of the database. Finally, Zebrabase also features an interactive breeding history and a smart interface with advanced visualizations and intuitive color coding allowing to speed up the processes.
A high-throughput in vitro translation screen towards discovery of novel antimalarial protein translation inhibitors
Authors: Baumann Hella , Matthews Holly , Li Mengqiao , Hu Jenny J. , Willison Keith R. , Baum Jake 
Published: January 2018

ABSTRACTDrugs that target protein synthesis are well-validated for use as antimicrobials, yet specific high throughput (HTP) methods to screen for those targeting malaria are lacking. Here, we have developed a cell free in vitro translation (IVT) assay for the human malaria parasite, Plasmodium falciparum, which reconstitutes the native parasite protein translation machinery. Combining clarified IVT lysate with a click beetle luciferase reporter gene fused to untranslated regions of Pf histidine-rich proteins (hrp)-2 and 3, the HTP IVT assay accurately reports protein translation in a 384-well plate format using a standard spectrofluorometer. We validate the assay as effective in detecting compounds targeting the ribosome, ribosome co-factors (elongation factor 2) and cytosolic tRNA synthetases as well as its ability to find translation inhibitors in a blind screen using a high-density assay format amenable for high throughput. This demonstrates an ability to reconstitute the breadth of the parasite eukaryotic protein translation machinery in vitro and use it as a powerful platform for antimalarial drug discovery.
Identifying differentially methylated sites in samples with varying tumor purity
Authors: Häkkinen Antti , Alkodsi Amjad , Facciotto Chiara , Zhang Kaiyang , Kaipio Katja , Leppä Sirpa , Carpén Olli , Grénman Seija , Hynninen Johanna , Hietanen Sakari , Lehtonen Rainer , Hautaniemi Sampsa 
Published: January 2018

AbstractDNA methylation aberrations are common in many cancer types. A major challenge hindering comparison of patient-derived samples is that they comprise of heterogeneous collection of cancer and microenvironment cells. We present a computational method that allows comparing cancer methylomes in two or more heterogeneous tumor samples featuring differing, unknown fraction of cancer cells. The method is unique in that it allows comparison also in the absence of normal cell control samples and without prior tumor purity estimates, as these are often unavailable or unreliable in clinical samples. We use simulations and next-generation methylome, RNA, and whole-genome sequencing data from two cancer types to demonstrate that the method is accurate and outperforms alternatives. The results show that our method adapts well to various cancer types and to a wide range of tumor content, and works robustly without a control or with controls derived from various sources. The method is freely available athttps://bitbucket.org/anthakki/dmml.
Comparative transcriptomics reveals a conserved Bacterial Adaptive Phage Response (BAPR) to viral predation
Authors: Blasdel Bob G. , Ceyssens Pieter-Jan , Chevallereau Anne , Debarbieux Laurent , Lavigne Rob 
Published: January 2018

AbstractIntrinsic and acquired defenses against bacteriophages, including Restriction/Modification, CRISPR/Cas, and Toxin/Anti-toxin systems have been intensely studied, with profound scientific impacts. However, adaptive defenses against phage infection analogous to adaptive resistance to antimicrobials have yet to be described. To identify such mechanisms, we applied an RNAseq-based, comparative transcriptomics approach in differentPseudomonas aeruginosastrains after independent infection by a set of divergent virulent bacteriophages. A common host-mediated adaptive stress response to phages was identified that includes the Pseudomonas Quinolone Signal, through which infected cells inform their neighbors of infection, and what may be a resistance mechanism that functions by reducing infection vigor. With host transcriptional machinery left intact, we also observe phage-mediated differential expression caused by phage-specific stresses and molecular mechanisms. These responses suggest the presence of a conserved Bacterial Adaptive Phage Response mechanism as a novel type of host defense mechanism, and which may explain transient forms of phage persistence.
ExomeSlicer: a resource for the development and validation of exome-based clinical panels
Authors: Niazi Rojeen , Gonzalez Michael A. , Balciuniene Jorune , Evans Perry , Sarmady Mahdi , Abou Tayoun Ahmad N. 
Published: January 2018

AbstractExome-based panels (exome slices) are becoming the preferred diagnostic strategy in clinical laboratories, especially for genetically heterogeneous disorders. The advantages of this approach include enabling frequent updates to gene content without the need for re-designing, reflexing to exome analysis bioinformatically without requiring additional sequencing, and streamlining laboratory operation by using established exome kits and protocols. Despite their increasing use, there are currently no guidelines or appropriate resources to support their clinical implementation. Here, we highlight principles and important considerations for the clinical development and validation of exome-based panels, guided by clinical data from a diagnostic epilepsy panel using this approach. We also present a novel, publically accessible web-based resource, ExomeSlicer, and demonstrate its clinical utility in predicting gene-specific and exome-wide technically challenging regions that are not amenable to Next Generation Sequencing (NGS), and that might significantly lead to increased post hoc Sanger fill in burden. Using this tool, we also characterize > 2000 low complexity, GC-rich and/or high homology, regions across the exome that can be a source of false positive or false negative variant calls thus potentially leading to misdiagnoses in tested patients.