bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of the E-Value to Assess Bias in Observational Research in Plastic Surgery
Authors: Baxter Natalie B. , Kocheril Alex , Chung Kevin C. 
Published: September 2022

Background:
The E-value is a statistical measure that is used to quantify the degree of unmeasured confounding that is necessary to undermine the treatment-outcome associations established in observational studies. Despite the substantial amount of observational research that informs evidence-based practice in plastic surgery, sensitivity analyses based on the E-value have not been conducted in the field.

Methods:
We performed a systematic search of the literature to identify meta-analyses of observational studies in plastic surgery. We calculated E-values for various treatment-outcome associations based on the risk, odds, or hazard ratios in each study, to assess unmeasured confounding effects that may influence the validity of the conclusions. We then analyzed the distribution of E-values from pooled versus individual studies.

Results:
We identified 45 meta-analyses that met the inclusion criteria, with each containing an average of 3 pooled assessments of observational data. The E-value of the pooled effect estimates ranged from 1.11 to 19.49, with an average value of 3.82. As for the individual effect estimates from each primary study within the meta-analyses, the E-values ranged from 1.00 to 321.50, with an average value of 8.74.

Conclusions:
We determined that E-values vary substantially across the literature and that unmeasured confounding may be present in a substantial number of observational studies. Although extant statistical techniques will continue to be necessary to control for measured confounding, the E-value is a novel concept that can facilitate more robust sensitivity analyses in plastic surgery research.
A novel method of fibula flap in situ distraction osteogenesis prior to flap transfer
Authors: Purnell Chad A , Aasen Margaret , Alkureishi Lee WT , Dumanian Gregory A , Patel Pravin K 
Published: September 2022

Purpose:
The fibula flap is the workhorse for mandibular reconstruction, but fibula bone width is not ideal to match mandibular height. In this study, in-situ widening of the fibula with distraction osteogenesis prior to transfer is evaluated as a solution. We present a proof of concept of this technique with a patient series, including one patient who has undergone subsequent orthognathic surgery of their reconstructed mandible.

Methods:
A retrospective review of patients undergoing our technique was performed. A longitudinal fibula osteotomy is made in situ, and distraction is performed in the leg to widen the fibula. After distraction and consolidation periods, flaps were osteotomized and transferred to the mandible.

Results:
This technique was applied to three patients (ages 9, 11, and 13) with Pruzansky III mandibular hypoplasia at our institution over 15 years. In all cases, bony union was achieved. Mean surgical followup was 5 years. No significant morbidity occurred at the donor sites. Partial flap resorption was observed a number of years postoperatively in one patient. One patient developed TMJ ankylosis after closed treatment of an unrelated mandible fracture. One patient developed a sinus tract requiring debridement of a partial flap necrosis. One patient has gone on to have orthognathic surgery, including osteotomy of the fibula.

Conclusions:
In-situ fibula distraction osteogenesis is a novel technique to “pre-laminate" a fibula flap prior to transfer to the mandible. This method allows for the reconstruction of challenging mandibular defects without compromising bone height, pedicle length, or the ability to perform orthognathic surgery.
“A Multicenter Randomized Controlled Clinical Trial Evaluating Two Application Regimens of Dehydrated Human Amniotic Membrane and Standard of Care vs Standard of Care Alone in the Treatment of Venous Leg Ulcers”
Authors: Serena Thomas E. , Orgill Dennis P. , Armstrong David G. , Galiano Robert D. , Glat Paul , Carter Marissa , Kaufman Jarrod , Li William , Zelen Charles M. 
Published: September 2022

Background:
An aseptically processed dehydrated human amnion and chorion allograft(dHACA) without terminal sterilization has been shown to improve healing rates in chronic wounds. This randomized controlled trial(RCT) evaluated the safety and effectiveness of weekly and biweekly applications of dHACA plus Standard of Care (SOC) compared to SOC alone on chronic venous leg ulcers (VLUs).

Methods:
This open-label RCT included patients with chronic VLUs at 8 wound care centers across the United States. The primary endpoint was the proportion of healed ulcers at 12 weeks. Secondary endpoints included the proportion of ulcers achieving 40% closure at 4 weeks and the incidence of adverse events (AEs).

Results:
Among 101 patients screened for eligibility, 60 were eligible and enrolled. At 12 weeks, significantly more VLUs healed in the two dHACA-treated groups (30/40, 75%) than in the SOC group (6/20, 30%), p = 0.001. Treatment with dHACA remained significant after adjustment for wound area (p = 0.002), with an odds ratio of 8.7 (95% confidence interval: 2.2-33.6). Only six VLUs (30%) healed in the SOC group compared to 15 (75%) in the weekly dHACA group (p = 0.02) and 15 (75%) in the biweekly dHACA group (p =0.02). There were no significant differences in the proportion of wounds with percent area reduction (PAR ) ≥40% at 4 weeks among all groups. The AE rate was 63.5%. Among the 38 AEs, none were graft- or procedure-related, and all were resolved with appropriate treatment.

Conclusions:
The adjunctive treatment of chronic VLUs with dHACA and SOC, regardless of weekly or biweekly application, significantly healed more VLUs than SOC alone, suggesting that the use of aseptically processed dHACA is advantageous as well as a safe and effective treatment option in the healing of chronic VLUs.
CRF neurons establish resilience via stress-history dependent BNST modulation
Authors: Haynes Sherod E , Lacagnina Anthony , Seong Hyun Seo , Afzal Muhammad , Morel Carole , Menigoz Aurelie , Rajan Kanaka , Clem Roger L , Mayberg Helen S , Rannie Donald G. , Young Larry J. , Han Ming-Hu 
Published: September 2022

AbstractCumulative stress is a major risk factor for developing major depressive disorder (MDD), yet not everyone experiencing chronic stress develops MDD. In those who do not, it is unclear at what point, or by what mechanism, a trajectory of stable resiliency emerges. Utilizing a 10-day repeated social defeat stress model (RSDS) for MDD, we observed that a critical period between 7 and 10 daily defeats marks the phenotypical divergence of resilient from susceptible mice. In response to ongoing stress, corticotropin-releasing factor (CRF) neurons of the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) display a sustained increased firing rate in resilient, but not susceptible mice. This neurophysiological adaptation was self-sustaining, but only after 7 critical stress exposures, indicating that the process of developing resilience is dependent on stress history. Our study reveals a novel process by which individuals might persist in the face of adversity by way of stress-provoked activation, not inhibition of a key CRF limbic region that establishes a pathway to resilience.
Classification Of Mushrooms Using Artificial Neural Network
Authors: Gupta Aaditya Prasad 
Published: September 2022

ABSTRACTThe artificial neural network (ANN) has had remarkable success in pattern recognition in recent years. It stands for a new learning paradigm in artificial intelligence (AI) and machine learning and has been applied to problems ranging from speech recognition to the prediction of protein secondary structure, cancers, and gene prediction. Recent breakthrough results in image analysis and speech recognition have generated massive interest in this field. However, the mathematical and computational methodology underlying deep learning models is very challenging, especially for interdisciplinary scientists. In this manuscript, a Neural Network model is used to classify whether a given mushroom is edible or poisonous using Tensorflow in Python based on the attributes present in the dataset. The dataset includes descriptions of hypothetical samples corresponding to 23 species of gilled mushrooms in the Agaricus and Lepiota Family Mushroom, drawn from The Audubon Society Field Guide to North American Mushrooms (1981).
Plasticity in Na+/K+-ATPase thermal kinetics drives variation in the critical thermal minimum of adult Drosophila melanogaster
Authors: Andersen Mads Kuhlmann , Robertson R. Meldrum , MacMillan Heath A. 
Published: September 2022

AbstractThe majority of insects can acclimate to changes in their thermal environment and counteract temperature effects on neuromuscular function. At the critical thermal minimum a spreading depolarization (SD) event silences central neurons, but the temperature at which this event occurs can be altered through acclimation. SD is triggered by an inability to maintain ion homeostasis in the extracellular space in the brain and is characterized by a rapid surge in extracellular K+ concentration, implicating ion pump and channel function. Here, we focused on the role of the Na+/K+-ATPase specifically in lowering the SD temperature in cold-acclimated D. melanogaster. After first confirming cold acclimation altered SD onset, we investigated the dependency of the SD event on Na+/K+-ATPase activity by injecting an inhibitor, ouabain, into the head of the flies to induce SD over a range of temperatures. Latency to SD followed the pattern of a thermal performance curve, but cold acclimation resulted in a left-shift of the curve to an extent similar to its effect on the SD temperature. With Na+/K+-ATPase activity assays and immunoblots, we found that cold-acclimated flies have ion pumps that are less sensitive to temperature, but do not differ in their overall abundance in the brain. Combined, these findings suggest a key role for plasticity in Na+/K+-ATPase thermal sensitivity in maintaining central nervous system function in the cold, and more broadly highlight that a single ion pump can be an important determinant of whether insects can respond to their environment to remain active at low temperatures.
CIRKO: A chemical-induced reversible gene knockout system for studying gene function in situ
Authors: Shi Hui , Jin Qin , Chen Fangbing , Ouyang Zhen , Gou Shixue , Liu Xiaoyi , Li Lei , Mu Shuangshuang , Lai Chengdan , Zhang Quanjun , Ye Yinghua , Wang Kepin , Lai Liangxue 
Published: September 2022

AbstractConditional loss and restoration of function are becoming important approaches for investigating gene function. Given that reversible conditional gene knockouts in cells required complicated manipulation, conditional inactivation and reactivation of a gene in primary somatic cells with limited proliferative capacity and in animal models remain difficult to achieve. Here, we first developed a reportable and reversible conditional intronic cassette (ReCOIN), wherein inactivation and reactivation of the gene are mediated via sequential expression of Cre and Flp recombinases, respectively. The expression pattern of the target gene can be monitored by direct visualization. To simply and tightly control temporal expression of the recombinases, on the basis of ReCOIN, we further presented a dual chemical-induced reversible gene knockout system (CIRKO) by insertion of reverse tetracycline transcriptional activator (rtTA) and tetracycline response element (TRE)-controlled Cre and FlpoERT2 recombinases cassettes into Rosa26 and Hipp11 loci of cells, respectively, in which transcription termination of the target gene can be induced at a specific stage in the presence of doxycycline, while gene restoration is achieved in the presence of doxycycline and tamoxifen simultaneously. This system provides a simple, rapid, and flexible gene switch for studying gene function in situ both in vitro and in vivo.Impact statementA novel chemical-induced reversible gene knockout system provides a simple, rapid, and flexible gene switch to facilitate the study of gene function in primary somatic cells in vitro, embryos in vitro or in vivo, and animals in vivo.
Magnetic Resonance Spectroscopy Spectral Registration Using Deep Learning
Authors: Ma David J. , Yang Yanting , Harguindeguy Natalia , Tian Ye , Guo Jia 
Published: September 2022

AbstractA novel convolutional neural network based spectral registration (CNN-SR) approach is introduced to achieve efficient and accurate simultaneous frequency-and-phase correction (FPC) of single-voxel MEGA-PRESS magnetic resonance spectroscopy (MRS) data. For this approach, one neural network was trained and validated using a published simulated and in vivo MEGA-PRESS MRS dataset with a wide-range of artificial frequency (0-20 Hz) and phase (0-90°) offsets applied. The proposed CNN-SR approach was subsequently tested and compared to the sequential FPC deep learning approaches and demonstrated more effective and accurate performance. Furthermore, a large random Gaussian signal-to-noise ratio (SNR 20 and SNR 2.5) and line broadening (0-20 ms) was introduced to the original simulated dataset to investigate our model performance compared to the other deep learning models. The testing showed that CNN-SR was a more accurate quantification tool and resulted in a lower SNR when compared with the other deep learning methods, due to having smaller mean absolute errors in both frequency and phase offset predictions. For Off spectra, the CNN-SR model was capable of correcting frequency offsets with 0.014 ± 0.010 Hz and phase offsets with 0.104 ± 0.076° absolute errors on average for unseen simulated data with SNR 20 and correcting frequency offsets with 0.678 ± 0.883 Hz and phase offsets with 2.367 ± 2.616° absolute errors on average at very low SNR (2.5) and line broadening (0-20 ms) introduced. In addition, we tested the simulated dataset with additional SNR and line broadening on a more refined model (CNN-SR+) where the pre-trained CNN-SR was further optimized by minimizing the difference between individual spectra and a common template with unsupervised learning. The performance on Off spectra was improved to 0.058 ± 0.050 Hz for correcting frequency offsets and to 0.416 ± 0.317° for correcting phase offsets. We further evaluated the ability of our model to process the published Big GABA in vivo dataset and CNN-SR+ achieved the best performance. Moreover, additional frequency and phase offsets (i.e., small, moderate, large) were applied to the in vivo dataset, and CNN-SR+ also demonstrated better performance for FPC when compared to the other deep learning models. These results indicate the utility of using deep learning for spectral registration and demonstrate the application of unsupervised learning in further improving the model to achieve state-of-the-art performance.
Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome
Authors: Jain Pritesh , Miller-Fleming Tyne , Topaloudi Apostolia , Yu Dongmei , Drineas Petros , Georgitsi Marianthi , Yang Zhiyu , Rizzo Renata , Müller-Vahl Kirsten R. , Tumer Zeynep , Mol Debes Nanette , Hartmann Andreas , Depienne Christel , Worbe Yulia , Mir Pablo , Cath Danielle C. , Boomsma Dorret I. , Roessner Veit , Wolanczyk Tomasz , Janik Piotr , Szejko Natalia , Zekanowski Cezary , Barta Csaba , Nemoda Zsofia , Tarnok Zsanett , Buxbaum Joseph D. , Grice Dorothy , Glennon Jeffrey , Stefansson Hreinn , Hengerer Bastian , Benaroya-Milshtein Noa , Cardona Francesco , Hedderly Tammy , Heyman Isobel , Huyser Chaim , Morer Astrid , Mueller Norbert , Munchau Alexander , Plessen Kerstin J , Porcelli Cesare , Walitza Susanne , Schrag Anette , Martino Davide ,   The EMTICS collaborative group, Dietrich Andrea ,   The TS-EUROGRAIN Network, Mathews Carol A. , Scharf Jeremiah M. , Hoekstra Pieter J. , Davis Lea K. , Paschou Peristera 
Published: September 2022

AbstractTourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders.
Human blood vessel organoids reveal a critical role for CTGF in maintaining microvascular integrity
Authors: Romeo Sara G , Secco Ilaria , Schneider Edoardo , Reumiller Christina M , Santos Celio XC , Pooni Aman , Yin Xiaoke , Theofilatos Konstantinos , Trevelin Silvia Cellone , Zeng Lingfang , Mann Giovanni E , Margariti Andriana , Mayr Manuel , Shah Ajay M , Giacca Mauro , Zampetaki Anna 
Published: September 2022

AbstractThe microvasculature plays a key role in tissue perfusion, transport of mediators, and exchange of gases and metabolites to and from tissues. Microvascular dysfunction has emerged as an important contributor to cardiovascular diseases. In this study we used human blood vessel organoids (BVOs) as a model of the microvasculature to delineate the mechanisms of microvascular dysfunction caused by metabolic rewiring. BVOs fully recapitulated key features of the normal human microvasculature, including reliance of mature endothelial cells (ECs) on glycolytic metabolism, as concluded from metabolic flux assays using13C-glucose labelling and mass spectrometry-based metabolomics. Treatment of BVOs with PFK15, a pharmacological inhibitor of glycolysis, resulted in rapid tissue restructuring, vessel regression with reduced pericyte coverage and alterations in tight junction morphology. Proteomic analysis of the BVO secretome revealed remodelling of the extracellular matrix and differential expression of paracrine mediators such as CTGF. Treatment with recombinant CTGF recovered tight junction formation and increased pericyte coverage in microvessels. Our metabolic and proteomics findings demonstrate that BVOs rapidly undergo restructuring in response to metabolic changes and identify CTGF as a critical paracrine regulator of microvascular integrity.
20E-dependent tyrosine phosphorylation of phospholipase C gamma underpins egg development in the malaria vectorAnopheles gambiae
Authors: Ferracchiato Simona , Catteruccia Flaminia , Peirce Matthew J. 
Published: September 2022

ABSTRACTThe efficient development of eggs following a blood meal is central to the vector capacity ofAnopheles gambiaefemales. The ecdysteroid hormone 20-hydroxyecdysone (20E) plays a pivotal role in this process, yet the signaling mechanisms by which 20E exerts its effects remain incompletely understood. Here we show blood feeding is associated with increased tyrosine phosphorylation of an array of proteins coincident with the increase in titers of 20E that follows a blood meal. Injection of genistein, a tyrosine kinase inhibitor, reduces both the appearance of phosphotyrosine-containing proteins and fecundity, linking tyrosine phosphorylation to egg development. We identify one of the proteins phosphorylated after a blood meal as phospholipase C gamma (PLCγ) and show that its blood feeding-induced phosphorylation is dependent on endogenously synthesized 20E via the ecdysone receptor (EcR). Interruption of Src-like tyrosine kinase signaling inhibits phosphorylation of PLCγ as well as egg development after blood feeding, implicating Src-like kinases in the phosphorylation of PLCγ. Taken together, these data suggest that the effects of 20E onAn. gambiaeegg development are at least partially mediated through a tyrosine phosphorylation-dependent signaling cascade involving Src family tyrosine kinases and PLCγ.
A new strategy for identifying polysialylated proteins reveals they are secreted from cancer cells as soluble proteins and as part of extracellular vesicles
Authors: Hunter Carmanah , Derksen Tahlia , Karathra Julieanna , Baker Kristi , Nitz Mark , Willis Lisa M. 
Published: September 2022

AbstractPolysialic acid (polySia) is a long homopolymer consisting of α2,8-linked sialic acid with tightly regulated expression in humans. In healthy adults, it occurs on cell surface glycoproteins in neuronal, reproductive, and immune tissues; however, it is aberrantly present in many cancers and its overexpression correlates with significantly increased metastasis and poor prognosis. Prompted by the observation that the MCF-7 breast cancer cell line contains only intracellular polySia, we investigated the secretion of polySia from MCF-7 cells. PolySia was found predominantly on soluble proteins in MCF-7 conditioned media, but also on extracellular vesicles (EVs), secreted from the cells. Since MCF-7 cells do not express known polysialylated proteins, we developed a robust method for purifying polysialylated proteins that uses a metabolic labelling strategy to introduce a bioorthogonal functionality into polySia. Using this method we identified three previously unknown polysialylated proteins, and found that two of these proteins - AGR2 and QSOX2 – were secreted from MCF-7 cells. We confirmed that QSOX2 found in EV-depleted MCF-7 cell conditioned media was polysialylated. Herein we report the secretion of polysialic acid on both soluble and EV-associated proteins from MCF-7 cancer cells and introduce a new method to efficiently identify polysialylated proteins. These findings have exciting implications for understanding the roles of polySia in cancer progression and metastasis and for identifying new cancer biomarkers.