Top 10 Biorxiv Papers Today in Pathology


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#1. Digital ischemia: Etiologies and long-term follow up. A cohort study of 323 patients
Alizée RAIMBEAU, Marc-Antoine Pistorius, Yann Goueffic, Jérôme Connault, Pierre Plissonneau-Duquene, Blandine Maurel, Jean Reignier, Karim Asehnoune, Mathieu Artifoni, Quentin Didier, Giovanni Gautier, Jean-Nöel Trochu, Bertrand Rozec, Chan N’Gohou, Cécile Durant, Pierre Pottier, Bernard Planchon, Christian Agard, Olivier Espitia
Abstract Aim: Upper Extremity Digital ischemia (UEDI) is a rare heterogeneous condition with digital upper limb ischemia occurring forty times less frequently than toe ischemia. Using the largest cohort ever published, the aim of this study was to evaluate etiologies, treatments, prognosis and long-term clinical outcomes of DI. Method: Patients included had UEDI with or without cutaneous necrosis. They were followed in a university hospital setting between January 2000 to December 2016. Etiologies, recurrence of UEDI, digital amputation and overall survival were analyzed retrospectively. Results: DI due to cardio-embolic disease (DICE) was the highest occurring etiology with 59 patients (18.3%), followed by UEDI due to Systemic Sclerosis (SSc) (16.1%), idiopathic causes (11.7%), Thromoboangitis obliterans (TAO) (9.3%), iatrogenic causes (9.3%) and cancer (6.2%). DICE patients tended to fall into an older age bracket and featured a greater numbers of cases with hypertension whereas TAO patients smoked more tobacco and cannabis....
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Sample Sizes : [7, 18, 7, 2, 8, 7, 4, 27, 14, 5, 323, 86, 25]
Authors: 19
Total Words: 4709
Unqiue Words: 1671

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#2. A GYS2/p53 negative feedback loop restricts tumor growth in HBV-related hepatocellular carcinoma
Shi-Lu Chen, Chris Zhiyi Zhang, Li-Li Liu, Shi-Xun Lu, Ying-Hua Pan, Chun-Hua Wang, Yang-Fan He, Cen-Shan Lin, Xia Yang, Dan Xie, Jing-Ping Yun
Hepatocarcinogenesis is attributed to the reprogramming of cellular metabolism as consequence of the alteration in metabolite-related gene regulation. Identifying the mechanism of aberrant metabolism is of great potential to provide novel targets for the treatment of hepatocellular carcinoma (HCC). Here, we demonstrated that glycogen synthase 2 (GYS2) restricted tumor growth in HBV-related HCC via a negative feedback loop with p53. Expression of GYS2 was significantly downregulated in HCC and correlated with decreased glycogen content and unfavorable patient outcomes. GYS2 overexpression suppressed, whereas GYS2 knockdown facilitated cell proliferation in vitro and tumor growth in vivo via modulating p53 expression. GYS2 competitively bound to MDM2 to prevent p53 from MDM2-mediated ubiquitination and degradation. Furthermore, GYS2 enhanced the p300-induced acetylation of p53 at K373/382, which in turn inhibited the transcription of GYS2 in the support of HBx/HDAC1 complex. In summary, our findings suggest that GYS2 serves as a...
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biorxivpreprint: A GYS2/p53 negative feedback loop restricts tumor growth in HBV-related hepatocellular carcinoma https://t.co/YUay8hgrlZ #bioRxiv
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Sample Sizes : None.
Authors: 11
Total Words: 8819
Unqiue Words: 2542

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#3. A conserved role of the insulin-like signaling pathway in uric acid pathologies revealed in Drosophila melanogaster
Sven Lang, Neelanjan Bose, Kenneth Wilson, Deanna Brackman, Tyler Hilsabeck, Mark Watson, Jennifer Beck, Amit Sharma, Ling Chen, David Killilea, Sunita Ho, Arnold Kahn, Kathleen Giacomini, Marshall Stoller, Thomas Chi, Pankaj Kapahi
Elevated uric acid (UA) is a key factor for disorders, including gout or kidney stones and result from abrogated expression of Urate Oxidase (Uro) and diet. To understand the genetic pathways influencing UA metabolism we established a Drosophila melanogaster model with elevated UA using Uro knockdown. Reduced Uro expression resulted in the accumulation of UA concretions and diet-dependent shortening of lifespan. Inhibition of insulin-like signaling (ILS) pathway genes reduced UA and the concretion load. In humans, SNPs in the ILS genes AKT2 and FOXO3 were associated with UA levels or gout, supporting a conserved role for ILS in modulating UA metabolism. Downstream of the ILS pathway UA pathogenicity was mediated partly by NADPH Oxidase, whose inhibition attenuated the reduced lifespan and concretion accumulation. Thus, genes in the ILS pathway represent potential therapeutic targets for treating UA associated pathologies, including gout and kidney stones.
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Authors: 16
Total Words: 8677
Unqiue Words: 3237

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#4. Bilateral asymmetry favours the left hemimandibular side in companion rabbits
Pere M. Pares-Casanova, Maria Cabello, Baba Gana Gambo, Michael Oluwale Samuel, James Olukayode Olopade
Directional asymmetry (DA) appears when the left and right body sides differ consistently from each other. This asymmetry is characterized as a type of natural asymmetry typical of the population's biology, which can be derived both from genetic inheritance, as of the functional importance acquired by certain features with respect to the environment in which they develop. We report here preliminary findings that for the first time to quantify size asymmetry mandibles of companion rabbits. A total sample of 64 companion rabbits from the same farm were studied by means of geometric morphometric techniques. The mandible morphology was described by a set of 18 landmarks and semilandmarks on the lateral aspect. Tests showed paired differences with variations in distributions, demonstrating a DA in favour of left mandibular side. The detected unilaterality could be interpreted as a manifestation of lateralized masticatory activity. This is a first time report to quantify size asymmetry in this species.
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Authors: 5
Total Words: 4184
Unqiue Words: 1928

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#5. The effect of anti-IL-6 receptor antibody for the treatment of McH-lpr/lpr-RA1 mice that spontaneously developed ankylosing arthritis
Yu Mori, Takuya Izumiyama, Kazu Takeda, Naoko Mori, Shiro Mori, Tetsuya Kodama, Eiji Itoi
[Background] McH-lpr/lpr-RA1 mice are a new strain of mice which spontaneously develop arthritis in the ankle, leading finally to ankylosis. There is no published data that drug treatment has been trialed on these mice. [Objectives] This study examined the effect of the mouse anti-IL-6 receptor antibody, MR16-1, for the treatment of ankylosis in McH-lpr/lpr-RA1 mice. [Methods] Male McH-lpr/lpr-RA1 mice were randomly divided into control and treatment groups. MR16-1 was administered from 10 weeks of age for the treatment group. Saline was applied for the control group. The drug was administered once a week, at an initial dose of 2 mg, then maintained at 0.5 mg once per week thereafter. The effects were evaluated by the histopathological synovitis score, in vivo imaging using indocyanine green liposomes, and analysis of the gene expression of inflammatory cytokines. [Results] Tissue analyses were carried out at 14, 17 and 20 weeks of age. The synovitis scores of treated groups were significantly lower compared with those of the...
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biorxivpreprint: The effect of anti-IL-6 receptor antibody for the treatment of McH-lpr/lpr-RA1 mice that spontaneously developed ankylosing arthritis https://t.co/vXeb6Ixtho #bioRxiv
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Sample Sizes : [5, 5, 5, 5, 5]
Authors: 7
Total Words: 6530
Unqiue Words: 2341

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#6. Enhanced β-secretase processing of amyloid precursor protein in the skeletal muscle of ALS animal models
Huaqiang Yang
Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disorder primarily characterized by motor neuron degeneration and muscle paralysis. Several studies indicate that pathological changes in the skeletal muscle contribute to disease progression. We report a significant increase of β-secretase processing of amyloid precursor protein (APP) in the skeletal muscle but not the spinal cord or cerebral cortex of hSOD1 (G93A) transgenic ALS mouse models. Enhanced β-secretase processing of APP was manifested by up-regulated expression of βCTF, the 22-kd CTF of APP, and β-secretase processing enzyme, BACE1. Morphological analysis demonstrated that enhanced β-secretase processing of APP mainly occurred in the atrophic myofibers of ALS mice. We also observed a similar change in APP processing in an hSOD1 (G93A) transgenic ALS pig model, suggesting that enhanced β-secretase processing of APP in skeletal muscle may be a common pathological feature of ALS. These findings reveal a selective change in APP processing in skeletal muscle...
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Sample Sizes : None.
Authors: 1
Total Words: 5808
Unqiue Words: 1733

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#7. Luigi: Large-scale histopathological image retrieval system using deep texture representations
Daisuke Komura, Keisuke Fukuta, Ken Tominaga, Akihiro Kawabe, Hirotomo Koda, Ryohei Suzuki, Hiroki Konishi, Toshikazu Umezaki, Tatsuya Harada, Shumpei Ishikawa
Background: As a large number of digital histopathological images have been accumulated, there is a growing demand of content-based image retrieval (CBIR) in pathology for educational, diagnostic, or research purposes. However, no CBIR systems in digital pathology are publicly available. Results: We developed a web application, the Luigi system, which retrieves similar histopathological images from various cancer cases. Using deep texture representations computed with a pre-trained convolutional neural network as an image feature in conjunction with an approximate nearest neighbor search method, the Luigi system provides fast and accurate results for any type of tissue or cell without the need for further training. In addition, users can easily submit query images of an appropriate scale into the Luigi system and view the retrieved results using our smartphone application. The cases stored in the Luigi database are obtained from The Cancer Genome Atlas with rich clinical, pathological, and molecular information. We tested the...
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Authors: 10
Total Words: 5414
Unqiue Words: 2041

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#8. β-lactam Antibiotics Stimulate the Pathogenicity of Methicillin-resistant Staphylococcus aureus Via SarA-controlled Tandem Lipoprotein Expression
Weilong Shang, Yifan Rao, Ying Zheng, Yi Yang, Qiwen Hu, Zhen Hu, Jizhen Yuan, Huagang Peng, Kun Xiong, Li Tan, Shu Li, Junmin Zhu, Ming Li, Xiaomei Hu, Xuhu Mao, Xiancai Rao
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of nosocomial infections worldwide. MRSA resists nearly all β-lactam antibiotics that have a bactericidal activity and a signal inducer effect. However, studies have yet to clarify whether the inducer effect of empirically used β-lactams stimulates MRSA pathogenicity in vivo. Here, we showed that a new cluster of tandem lipoprotein genes (tlpps) was upregulated in MRSA in response to the subinhibitory concentrations of β-lactam induction. The increased Tlpps significantly altered immune responses by macrophages with high IL-6 and TNFα levels. The deletion of the tlpps mutant (N315Δtlpps) significantly decreased the proinflammatory cytokine levels in vitro and in vivo. The bacterial loads of N315Δtlpps in the mouse kidney were also reduced compared with those of the wild type N315. The β-lactam-treated MRSA exacerbated cutaneous infections with increased lesion size, extended illness, and flake-like abscess-formation compared with those of the nontreatment. The...
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Authors: 16
Total Words: 11680
Unqiue Words: 3772

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#9. Wolbachia-infected Drosophila prefer cooler temperatures
Pieter Andrew Arnold, Samantha Levin, Aleksej L Stevanovic, Karyn Johnson
Temperature plays a fundamental role in host-pathogen interactions. Wolbachia is an endosymbiont that infects about 40% of arthropod species, which can affect host behaviour and reproduction. The effect of Wolbachia on host thermoregulatory behaviour is largely unknown. Here, we used a thermal gradient to test whether Drosophila melanogaster infected with Wolbachia exhibit different temperature preferences ( T p) to uninfected flies. We found that Wolbachia -infected flies preferred a cooler mean temperature ( T p = 25.06±0.25°C) than uninfected flies ( T p = 25.78±0.24°C). Our finding suggests that Wolbachia -infected hosts might seek out cooler microclimates to reduce exposure to and lessen the consequences of high temperatures.
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Authors: 4
Total Words: 3034
Unqiue Words: 1352

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#10. Guanabenz treatment improves Oculopharyngeal muscular dystrophy phenotype
Alberto Malerba, Fanny Roth, Pradeep Harish, Jamila Dhiab, Ngoc Lu-Nguyen, Ornella Cappellari, Susan Jarmin, Alexandrine Mahoudeau, Victor Ythier, Jeanne Laine, Elisa Negroni, Emmanuelle Abgueguen, Martine Simonelig, Philippe Guedat, Vincent Mouly, Gillian Butler-Browne, Cecile Voisset, George Dickson, Capucine Trollet
Oculopharyngeal muscular dystrophy (OPMD) is a rare late onset genetic disease affecting most profoundly eyelid and pharyngeal muscles, leading respectively to ptosis and dysphagia, and proximal limb muscles at later stages. A short abnormal (GCG) triplet expansion in the polyA-binding protein nuclear 1 (PABPN1) gene leads to PABPN1-containing aggregates in the muscles of OPMD patients. It is commonly accepted that aggregates themselves, the aggregation process and/or the early oligomeric species of PABPN1 are toxic in OPMD. Decreasing PABPN1 aggregate load in animal models of OPMD ameliorates the muscle phenotype. In order to identify a potential therapeutic molecule that would prevent and reduce aggregates, we tested guanabenz acetate (GA), an FDA-approved antihypertensive drug, in OPMD cells as well as in the A17 OPMD mouse model. We demonstrate that treating mice with GA reduces the size and number of nuclear aggregates, improves muscle force, protects myofibres from the pathology-derived turnover and decreases fibrosis. GA is...
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Myologie_Trans: Bravo! Capucine and colleagues! Guanabenz treatment improves Oculopharyngeal muscular dystrophy phenotype https://t.co/lBRw8hTtq6
LeGrandLab1: Great preprint on a new treatment for Oculopharyngeal muscular dystrophy by our colleagues. https://t.co/JlwwhhwQcn
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Sample Sizes : [6, 6, 6, 6, 7, 6, 3, 3, 6, 6, 6, 6, 6]
Authors: 19
Total Words: 11197
Unqiue Words: 3492

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