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Preprint ARTICLE | doi:10.20944/preprints202310.0978.v1

Oncostatin M’s Involvement in the Pathogenesis of Chronic Rhinosinusitis: Focus on Type 1 and 2 Inflammation

Chie Ishikawa, Sachio Takeno, Yukako Okamoto, Tomohiro Kawasumi, Takashi Kakimoto, Kota Takemoto, Manabu Nishida, Takashi Ishino, Takao Hamamoto, Tsutomu Ueda, Akio Tanaka

Subject: Medicine And Pharmacology, Otolaryngology Keywords: paranasal sinus; chronic rhinosinusitis; CRS; epithelial cell; eosinophil; oncostatin M; OSM; OSM receptor; OSMR

Online: 17 October 2023 (08:05:36 CEST)

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Preprint REVIEW | doi:10.20944/preprints202310.0889.v1

Postural Orthostatic Tachycardia Syndrome Following SARS-CoV-2 Infection and COVID-19 Vaccination: A Comparative Review

Zeinab Mohseni Afshar, Homa Mazaherinia, Hosein Nazari rostami, Arefeh Babazadeh, Mohammad Barary, Erfan Hashemi, Soheil Ebrahimpour

Subject: Public Health And Healthcare, Primary Health Care Keywords: Postural Orthostatic Tachycardia Syndrome (POTS); COVID-19; SARS-CoV-2; Vaccination

Online: 13 October 2023 (10:58:23 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202310.0859.v1

Comorbidity of Type 2 Diabetes and Dementia Among Hospitalized Patients in Los Angeles County, 2019-2021

D’Artagnan M. Robinson, Dalia Regos-Stewart, Mariana A Reyes, Tony Kuo, Noel C Barragan

Subject: Public Health And Healthcare, Public Health And Health Services Keywords: diabetes; Alzheimer’s disease; dementia; hospitalization

Online: 13 October 2023 (08:26:02 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202310.0713.v1

The Significance of Cathepsin B in Mediating Radiation Resistance in Colon Carcinoma Cell Line (Caco-2)

Ramadan F. Abdelaziz, Ahmed M. Hussein, Mohamed H. Kotob, Christina Weiss, Krzysztof Chelminski, Christian R. Studenik, Mohammed Aufy

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: colon cancer; cathepsin B; radiotherapy; radioresistance; cathepsin inhibitors; CA074

Online: 11 October 2023 (10:48:48 CEST)

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Cathepsins (Caths) are lysosomal proteases that participate in various physiological and pathological processes. Accumulating evidence suggests that cathepsins play a multifaceted role in radiotherapy response. Firstly, cathepsins contribute to the remodelling of the tumor microenvironment by degrading extracellular matrix components, promoting angiogenesis, and facilitating tumor invasion and metastasis. Their proteolytic activity influences the tumor's response to radiation by affecting oxygenation, nutrient availability, and immune cell infiltration within the tumor microenvironment. Furthermore, cathepsins have been implicated in DNA damage repair processes, including non-homologous end joining and homologous recombination. Cathepsin-mediated DNA repair mechanisms can promote radioresistance in cancer cells, limiting the efficacy of radiotherapy. Additionally, cathepsins have been associated with the activation of prosurvival signalling pathways, such as PI3K/Akt and NF-κB, which can confer resistance to radiation-induced cell death. Radiotherapy plays a crucial role in the treatment of various malignancies. However, the effectiveness of radiotherapy can be limited by intrinsic or acquired resistance mechanisms in cancer cells. In recent years, there has been growing interest in understanding the role of cathepsins, a family of proteases, in modulating the response of tumor cells to radiotherapy. In this study, we shed light on the regulation and expression of cathepsin B in colon carcinoma cell line (Caco-2) before and after exposure to radiation were investigated. Radiation-induced upregulation of cathepsin B in dose-independent manner. Proteolytic inhibition of cathepsin B by cathepsin B specific inhibitor CA074 has increased the cytotoxic effect of ionizing irradiation in caco-2 cells. Similar results were also obtained after cathepsin B knockout by CRISPR CAS9. These results showed that cathepsin B could contribute to ionizing radiation resistance and abolishing of cathepsin B either by inhibition its proteolytic activity or expression has increased in caco-2 cells susceptibility to ionizing irradiation.

Preprint ARTICLE | doi:10.20944/preprints202310.0184.v1

The Proinflammatory Effects of 25-Hydroxyvitamin D3 in New-Onset Type 2 Diabetes Mellitus and Prediabetes

Aysen Kutan Fenercioglu, Mustafa Sait Gonen, Hafize Uzun, Nurver Turfaner Sipahioglu, Gunay Can, Ebru Tas, Zehra Kara, Hande Mefkure Ozkaya, Pinar Atukeren

Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Prediabetes, type 2 diabetes mellitus, 25-hydroxyvitamin D3, inflammation, interleukins, TNF-α, NF-kB, MAPK

Online: 4 October 2023 (13:09:57 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202309.2082.v1

Failure of Non-invasive Respiratory Support in Patients with SARS-Cov-2 with the Different Therapies

Juan Javier García-Fernández, José Andrés Sánchez-Nicolás, Sonia Galicia-Puyol, Isabel Gil-Rosa, Juan Jose Guerras Conesa, Enrique Bernal-Morell, César Cinesi-Gómez

Subject: Medicine And Pharmacology, Internal Medicine Keywords: Non-invasive respiratory support 1; SARS-CoV-2 2; Hospitalization 3; CPAP 4; HFNO 5; Bilevel 6

Online: 29 September 2023 (10:41:45 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202309.1552.v1

Diverse Bioactive Secondary Metabolites from Aspergillus terreus: Antimicrobial, Anticancer and Anti- SARS-CoV-2 Activity Studies

Abdelaaty Hamed, Ahmed S. Abdel-Razek, AHMED B Abdelwahab, Ahmed El Taweel, Mohamed Gaballah, Norbert Sewald, Mohamed Shaaban

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: marine Aspergillus terreus; bioactive metabolites; antimicrobial; cytotoxicity; anti-coronavirus activities

Online: 22 September 2023 (10:07:13 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202309.0311.v1

Estimating Water Transparency in a Shallow Hypertrophic Lagoon (Albufera of Valencia, Spain) Using Sentinel-2 Images

Juan V. Molner, Juan M. Soria, Rebeca Pérez-González, Xavier Sòria-Perpinyà

Subject: Environmental And Earth Sciences, Remote Sensing Keywords: Secchi disk depth; water quality; remote sensing; eutrophication; optical modeling; water management

Online: 6 September 2023 (15:14:09 CEST)

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Preprint REVIEW | doi:10.20944/preprints202308.0520.v1

A Comprehensive Analysis of Structural and Functional Changes Induced by SARS-CoV-2 Spike Protein Mutations

Aganze Gloire-Aimé Mushebenge, Samuel Chima Ugbaja, Nonkululeko Avril Mbatha, Rene M. Khan, Hezekiel M. Kumalo

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: SARS-CoV-2; spike protein; mutations; viral infectivity; pathogenesis; vaccine efficacy; immune evasion; antibody neutralization; T-cell response; therapeutic targeting

Online: 7 August 2023 (10:12:28 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202308.0360.v1

SARS-CoV-2 in Domestic UK Cats from Alpha to Omicron: Swab Surveillance and Case Reports

Sarah Jones, Grace B. Tyson, Richard J. Orton, Katherine Smollett, Federica Manna, Kirsty Kwok, Nicolás M Suárez, Nicola Logan, Michael McDonald, Andrea Bowie, Ana Filipe, Brian J. Willett, William Weir, Margaret J. Hosie

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; coronavirus; pets; companion animals; reverse zoonosis; veterinary; animal welfare; feline; One Health

Online: 4 August 2023 (14:48:06 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202308.0056.v1

Antibody Response after 3 Dose Booster against SARS-CoV-2 mRNA Vaccine in Kidney Transplant Recipients

Domenico Tripodi, Roberto Dominici, Gennaro Santorelli, Rodolfo Rivera, Sandro Acquaviva, Marino Marchisio, Paolo Brambilla, Graziana Battini, Valerio Leoni

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Covid-19; antibody response; vaccination; kidney transplant recipients

Online: 1 August 2023 (10:38:45 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202307.0800.v1

Forest Monitoring Based on Sentinel-2 Satellite Imagery, Google Earth Engine Cloud Computing, and Machine Learning

Tamás Molnár, Géza Király

Subject: Biology And Life Sciences, Forestry Keywords: forest monitoring; remote-sensing; satellite image; bark beetle damage; Sentinel-2; vegetation index; water index

Online: 12 July 2023 (11:13:47 CEST)

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Preprint COMMUNICATION | doi:10.20944/preprints202307.0721.v1

Development of Highly Sensitive Anti-Mouse Epidermal Growth Factor Receptor 2 Monoclonal Antibodies for Flow Cytometry

Tsunenori Ouchida, Hiroyuki Suzuki, Tomohiro Tanaka, Mika K Kaneko, Yukinari Kato

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: mouse HER2; monoclonal antibody; cell-based Immunization and screening; CBIS

Online: 12 July 2023 (03:20:12 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202306.2087.v1

SARS-CoV-2 and Influenza Vaccine Hesitancy during the COVID-19 Pandemic in a Dynamic Perspective

Valentina Gerussi, Maddalena Peghin, Alvisa Palese, Maria De Martino, Elena Graziano, Stefania Chiappinotto, Federico Fonda, Giulia Bontempo, Tosca Semenzin, Luca Martini, Miriam Isola, Carlo Tascini

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Influenza; COVID-19; SARS-CoV-2; Green-Pass; Vaccination; Immunization; Vaccine-hesitancy; Pandemic

Online: 29 June 2023 (10:23:58 CEST)

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Preprint COMMUNICATION | doi:10.20944/preprints202306.2007.v1

Ct-Value from qRT-PCR Can Predict SARS-CoV-2 Virus Assembly and Lineage Assignment Success

Dominik Hadzega, Klaudia Babisova, Michaela Hyblova, Nikola Janostiakova, Peter Sabaka, Pavol Janega, Gabriel Minárik

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; RNA genome assembly; RT-qPCR; SPAdes

Online: 29 June 2023 (02:12:07 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202306.1238.v1

A Miniaturized System for Rapid, Isothermal Detection of SARS-CoV-2 in Human and Environmental Samples

Jake Staples, Athanasia-Maria Dourou, Irene Liampa, Calvin Sjaarda, Emily Moslinger, Henry Wong, Prameet Sheth, Stilianos Arhondakis, Ravi Prakash

Subject: Engineering, Bioengineering Keywords: loop-mediated isothermal amplification (LAMP); soft microfluidic chip; Nucleic Acid Tests; severe acute respiratory syndrome-coronavirus 2 (SARS-Cov-2); System-on-board Integrated Detector

Online: 16 June 2023 (12:02:22 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202306.0705.v1

Phenology-Based Winter Wheat Classification for Crop Growth Monitoring Using Multi-Temporal Sentinel-2 Satellite Data

Solomon W Newete

Subject: Biology And Life Sciences, Agricultural Science And Agronomy Keywords: Phenology; Tillering; Random Forest; Crop type; Clustering, Unsupervised classification

Online: 9 June 2023 (11:04:40 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202306.0624.v1

Oxidation Effects on Short-Term Creep Response in Air of Commercially Pure Titanium (CP-2 Ti)

Stefano Spigarelli, Michael Regev, Alberto Santoni

Subject: Chemistry And Materials Science, Metals, Alloys And Metallurgy Keywords: creep; oxidation; titanium; constitutive equations

Online: 8 June 2023 (10:18:37 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1536.v1

Evolution of Collective Sars-Cov-2 Humoral Immunity among the Population of the Republic of Belarus

Anna Y. Popova, Viacheslav Smirnov, Svetlana A. Egorova, Alexander A. Tarasenko, Alla M. Dashkevich, Angelika M. Milichkima, Angela L. Scuranovich, Irina V. Drozd, Iruna N. Glinskaya, Elena V. Zueva, Elena O. Samoilovich, Valery A. Ivanov, Edward S. Ramsay, Alexandra V. Gubanova, Victoria G. Drobyshevskaya, Oyuna B. Zhumbaeva, Olga A. Petrova, Alexandra P. Razumovskaya, Inna A. Karaban, Tamara V. Amvrosieva, Natalya P. Shmeleva, Ludmila V. Rubanic, Alina M. Dronina, Areg A. Totolian

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Republic of Belarus; population; SARS-CoV-2; COVID-19; seromonitoring; herd immunity; antibodies; nucleocapsid; receptor binding domain; vaccination; hybrid immunity

Online: 23 May 2023 (02:47:10 CEST)

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Background. The course of the COVID-19 epidemic process depends on population immunity which prevents pathogen spread among the population. Aim: to study the evolution of SARS-CoV-2 humoral immunity in the Belarusian population relative to COVID-19 pandemic dynamics. Materials and methods. The work was carried out according to a methodology for assessing population immunity developed by Rospotrebnadzor (Russia) and the Belarusian Ministry of Health with the participation of the St. Petersburg Pasteur Institute (SPPI), taking into account WHO recommendations. The study was approved by the Bioethics Committee of Belarus and the SPPI Bioethics Committee. Participant selection was carried out by questionnaire using a cloud (internet server) service. To monitor population immunity, a cohort of 4,661 people (participating in all stages of seromonitoring) was formed from the overall volunteer group. Volunteers were randomized by age group (1-17, 18-29, 30-39, 40-49, 50-59, 60-69, 70+ years), region, and professional group. For the detection of antibodies (Abs) to nucleocapsid (Nc) and S glycoprotein receptor-binding domain (RBD), corresponding assay systems were used following manufacturer instructions. The study was conducted in 4 stages according to a single scheme. Results. In the 1st stage (pandemic month 15), collective immunity was due mainly to Nc+RBD+ Ab status alone. By the 2nd stage (carried out after 4 months), their share decreased 1.2-fold, while the share of volunteers who had only RBD Abs increased 1.7-fold. In the 3rd and 4th stages (carried out after 9 and 19 months), the share of persons with RBD+Nc‒ compared to the 2nd stage decreased by 3.5%; the proportion of persons with Nc+RBD‒ Abs increased by 1.5-fold. The most important factor in population immunity was vaccination of the population, the coverage of which reached 70% by the 4th stage. Among vaccines, the Sputnik V and Sputnik Light vector designs were used most often. The whole-virion, inactivated BIBP-CorV vaccine was used less often. Conclusion. The evolution of collective SARS-CoV-2 humoral immunity included a set of changes in circulating Ab levels (Nc, RBD). The hybrid immunity formed helped to reduce the incidence to nearly zero.

Preprint ARTICLE | doi:10.20944/preprints202305.0797.v1

Graph Neural Network Based Efficient Subgraph Embedding 2 Method for Link Prediction in Mobile Edge Computing

XiaoLong Deng, JuFeng Sun, JunWen Lu

Subject: Computer Science And Mathematics, Data Structures, Algorithms And Complexity Keywords: link prediction; graph neural network; graph embedding

Online: 11 May 2023 (05:24:00 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.0432.v1

Persistence of SARS-Cov-2 Igg Antibody Response among South African Adults: A Prospective Cohort Study

Oladele Vincent Adeniyi, Oyewole Chris Durojaiye, Charity Masilela

Subject: Public Health And Healthcare, Public, Environmental And Occupational Health Keywords: SARS-CoV-2; COVID-19; Humoral immune response; Persistence; South Africa

Online: 8 May 2023 (03:29:35 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.0226.v1

Zn²⁺ and Cu²⁺ Interaction with the Recognition Interface of ACE2 for SARS-CoV-2 Spike Protein

Alessio Pelucelli, Massimiliano F Peana, Bartosz Orzeł, Elzbieta Gumienna-Kontecka, Serenella Medici, Maria Antonietta Zoroddu

Subject: Chemistry And Materials Science, Applied Chemistry Keywords: ACE2; peptides; zinc complexes; copper complexes; metal interaction; potentiometry; spectroscopy; NMR

Online: 4 May 2023 (08:09:22 CEST)

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Preprint REVIEW | doi:10.20944/preprints202304.0767.v1

Functional Foods: A Promising Strategy for Restoring Gut Microbiota Diversity Impacted by SARS-CoV-2 Variants

Antara Banerjee, Indumathi Somasundaram, Diptimayee Das, Samatha Jain M, Husaina Banu, Pavane MS, Sujay Paul, Atil Bisgin, Hong Zhang, Xiao-Feng Sun, Asim K Duttaroy, Surajit Pathak

Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: COVID-19; SARS-CoV-2; Gut microbiota; Variants; Probiotics; gut microbiota metabolites

Online: 23 April 2023 (04:34:31 CEST)

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Preprint REVIEW | doi:10.20944/preprints202304.0038.v1

Serological Response to SARS-CoV-2 after COVID-19 Vaccination in Lung Cancer patients: Short Review

Ananda Rodilla, Sooyun Tavolacci, Jazz Cagan, Tanay Shah, Sandeep Mittan, Philip C. Mack, Fred R. Hirsch

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: lung cancer; SARS-CoV-2 vaccine; immunogenicity

Online: 4 April 2023 (04:58:31 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202301.0013.v1

Characterization and Cellular Localization of a SFT-2/Got-1- like Transporter Protein of Leishmania infantum

Luiz A. Teixeira-Pinto, Guilherme C. Lechuga, Paloma Napoleão-Pêgo, Salvatore G. De-Simone

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Leishmania infantum; STF2/Got-1 family; cloning; cellular localization; membrane topology

Online: 3 January 2023 (07:38:58 CET)

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Preprint ARTICLE | doi:10.20944/preprints202212.0008.v1

Screening and Druggability Analysis of Marine Active Metabolites against SARS-CoV-2: An Integrative Computational Approach

Selvakumar Murugesan, Chinnasamy Ragavendran, Amir Ali, Safir Ullah Khan, Velusamy Arumugam, Dinesh Kumar Lakshmanan, Palanikumar Palanichamy, Manigandan Venkatesan, Chinnaperumal Kamaraj, Zia-ur-Rehman Mashwani, Muhammad Younas, Juan Pedro Luna-Arias, Fabian Fernández-Luqueño

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; molecular docking; ADMET; marine natural products; Chrysophaentin A; Hymenidin

Online: 1 December 2022 (03:51:30 CET)

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Preprint ARTICLE | doi:10.20944/preprints202209.0390.v1

Determination of SARS-CoV-2 Variants and Seroprevalence in Accra, Ghana during the Delta-Omicron Waves

Irene Owusu Donkor, Elvis Suatey Lomotey, Jewelna Akorli, Millicent Opoku, Emmanuel Frimpong Gyekye, Kojo M. Sedzro, Nana Efua Andoh, Yvonne Ashong, Benjamin Abuaku, Kwadwo Ansah Koram, Vincent Munster

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; asymptomatic; seroprevalence; Delta variant; Omicron variant; vaccination

Online: 26 September 2022 (09:41:01 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202209.0241.v1

Epidemiological and Clinical Features of SARS-CoV-2 Variants Circulating between April-December 2021 in Italy

Alessia Lai, Annalisa Bergna, Carla Della Ventura, Stefano Menzo, Bianca Bruzzone, Fabio Sagradi, Francesca Ceccherini-Silberstein, Alessandro Weisz, Nicola Clementi, Gaetano Brindicci, Ilaria Vicenti, Lolita Sasset, Sara Caucci, Benedetta Corvaro, Silvia Ippoliti, Carla Acciarri, Vanessa De Pace, Leonardo Lanfranchi, Maria Concetta Bellocchi, Giorgio Giurato, Roberto Ferrarese, Antonella Lagioia, Daniela Francisci, Martina Laura Colombo, Samuel Lazzarin, Matilde Ogliastro, Maria Rosa Cappelletti, Marco Iannetta, Francesca Rizzo, Carmen Rita Santoro, Chiara Fraccalvieri, Sophie Testa, Luca Carioti, Teresa Rocco, Annalisa Saracino, Annamaria Cattelan, Massimo Clementi, Loredana Sarmati, Agostino Riva, Spinello Antinori, Gianguglielmo Zehender

Subject: Biology And Life Sciences, Virology Keywords: variants circulation; SARS-CoV-2; Italy; epidemiology

Online: 16 September 2022 (08:07:10 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202208.0430.v1

Anticipating the Next Chess Move: Blocking SARS-CoV-2 Replication and Simultaneously Disarming Viral Escape Mechanisms

Samir Mansour Moraes Casseb, André Salim Khayat, Jorge Estefano Santana de Souza, Edivaldo Herculano Correa de Oliveira, Sidney Emanuel Batista dos Santos, Pedro Fernando da Costa Vasconcelos, Paulo Pimentel de Assumpção

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; siRNA; Treatment

Online: 25 August 2022 (10:00:27 CEST)

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The COVID-19 pandemic initiated a race to determine the best measures to control the disease and to save as many people as possible. Efforts to implement social distancing, the use of masks, and massive vaccination programs turned out to be essential in reducing the devastating effects of the pandemic. Nevertheless, the high mutation rates of SARS-CoV-2 challenge the vaccination strategy and maintain the threat of new outbreaks due to the risk of infection surges and even lethal variations able to resist the effects of vaccines and upset the balance. Most of the new therapies tested against SARS-CoV-2 came from already available formulations developed to treat other diseases, so they were not specifically developed for SARS-CoV-2. In parallel, the knowledge produced regarding the molecular mechanisms involved in this disease was vast due to massive efforts worldwide. Taking advantage of such a vast molecular understanding of virus genomes and disease mechanisms, a targeted molecular therapy based on siRNA specifically developed to reach exclusive SARS-CoV-2 genomic sequences was tested in a non-transformed human cell model. Since coronavirus can escape from siRNA by producing siRNA inhibitors, a complex strategy to simultaneously strike both the viral infectious mechanism and the capability of evading siRNA therapy was developed. The combined administration of the chosen produced siRNA proved to be highly effective in successfully reducing viral load and keeping virus replication under control, even after many days of treatment, unlike the combinations of siRNAs lacking this anti-anti-siRNA capability. Additionally, the developed therapy did not harm the normal cells, which was demonstrated because, instead of testing the siRNA in nonhuman cells or in transformed human cells, a non-transformed human thyroid cell was specifically chosen for the experiment. The proposed siRNA combination deeply reduced the viral load throughout the experiment and allowed cellular recovery, thus representing a potential innovation, to be considered as an additional weapon for therapy of COVID-19 and even other infectious diseases.

Preprint ARTICLE | doi:10.20944/preprints202207.0426.v1

Predicting the Cross-Coordinated Immune Response Dynamics in Sars-Cov-2 Infection: Implications for Disease Pathogenesis

Dmitry Grebennikov, Antonina Karsonova, Marina Loginova, Valentina Casella, Andreas Meyerhans, Gennady Bocharov

Subject: Computer Science And Mathematics, Applied Mathematics Keywords: SARS-CoV-2 infection; innate immune response; antigen-specific immune response; kinetic coordination; mathematical model; pathogenesis, long COVID-19

Online: 27 July 2022 (15:11:44 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202207.0384.v1

Clinical and Evolutionary Features of SARS Cov-2 Infection (COVID-19) in Children, A Romanian Perspective

George Jugulete, Daniela Pacurar, Mirela Luminita Pavelescu, Mihaela Safta, Elena Gheorghe, Bianca Borcos, Carmen Pavelescu, Mihaela Oros, Madalina Merisescu

Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: SARS-CoV-2; COVID-19; children; clinical features; comorbidities; male genderSARS-CoV-2, COVID-19, children, clinical features, comorbidities, male gender

Online: 26 July 2022 (04:43:02 CEST)

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Background: Given the potential for additional development to clarify a better knowledge of the overall impact of COVID-19 on the pediatric population, the clinical symptoms of SARS-CoV-2 infection in children and adolescents are still being explored. Morbidity in children is characterized by a variable clinical course. Our study's goal was to compare clinical aspects of 230 pediatric patients who tested positive for SARS-CoV-2 and were hospitalized between April 2020 and March 2022. Methods: In a retrospective analysis, we compared two groups hospitalized in the infectious diseases clinical ward IX at the National Institute for Infectious Diseases "Prof. Dr. Matei Bals," Bucharest, Romania. The first group of 88 patients was admitted between (April–December 2020) and their clinical manifestations were compared with the second group of 142 children followed between July 2021 and March 2022. Results: Of 230 children, the median age was 4.5 (interquartile range 0.6-17) years, 53.9% were male. 88 (36.21%) patients (first group) were admitted during the second wave in Romania, mostly aged < 5 years old, and experienced digestive manifestations like fever (p=0.001), and diarrhoea (p=0.004). The second group experienced different clinical signs when compared with the first group, with higher temperature and increased respiratory symptoms analogous to those of acute respiratory viral infections. The proportion in the second group increased, and 64.5% had symptoms for a median interval of 5 days; age (0-4 -years old) and length of stay were both proportionally inversely (p<0.01) and with correlation with hospital admission (p = 0.04). We report two Paediatric Inflammatory Multisystem Syndrome (PIMS) in the second group, with favourable evolution under treatment. Comorbidities were risk factors for complications appear (p < 0.001) in both groups. All paediatric cases admitted to our clinic evolved favourably and no death was recorded. Conclusions: In the first group children experienced digestive symptoms, whereas the second group experienced mild and moderate respiratory symptoms. We confirmed risk factors for severe cases as manifestations across the age spectrum, 0-4 (digestive symptoms) and 5-12 years old (for respiratory symptoms), associated comorbidities, fever, and male gender. The potential effects of COVID-19 infection in children older than 5 years should encourage caregivers to vaccinate and improve the prognosis among pediatric patients at risk.

Preprint ARTICLE | doi:10.20944/preprints202207.0380.v1

Molecular Mimicry between SARS-CoV-2 and Human Endocrinocytes: A Prerequisite of Post-COVID Endocrine Autoimmunity

Leonid P. Churilov, Muslimbek G. Normatov, Vladimir J. Utekhin

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; COVID-19; autoantibodies; autoimmune endocrinopathies; long-COVID syndrome; molecular mimicry; thyroid gland; adrenals; pituitary; Langerhans’ islets

Online: 26 July 2022 (03:42:01 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202203.0319.v1

Unveiling the Mechanisms of High-temperature 1/2[111] Screw Dislocation Glide in Iron--Carbon Alloys

Ivaylo Hristov Katzarov, Ljudmil Borisov Drenchev

Subject: Chemistry And Materials Science, Metals, Alloys And Metallurgy Keywords: dislocations; diffusion; FeC; Dynamic strain aging

Online: 24 March 2022 (02:20:36 CET)

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Preprint ARTICLE | doi:10.20944/preprints202203.0229.v1

MALDI-TOF-MS-Based Identification of Monoclonal Murine Anti-SARS-CoV-2 Antibodies Within One Hour

Georg Tscheuschner, Melanie N. Kaiser, Jan Lisec, Denis Beslic, Thilo Muth, Maren Krüger, Hans-Werner Mages, Brigitte G. Dorner, Julia Knospe, Jörg A. Schenk, Frank Sellrie, Michael G. Weller

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV-2 antibody; reproducibility crisis; peptide mass fingerprinting; monoclonal antibody; trace-ability; identity; antibody identification; antibody light chain; MALDI-TOF-MS

Online: 16 March 2022 (10:01:41 CET)

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During the SARS-CoV-2 pandemic, many virus-binding monoclonal antibodies have been developed for clinical and diagnostic purposes. This underlines the importance of antibodies as universal bioanalytical reagents. However, little attention is given to the reproducibility crisis that scientific studies are still facing to date. In a recent study, not even half of all research antibodies mentioned in publications could be identified at all. This should spark more efforts in the search for practical solutions for the traceability of antibodies. For this purpose, we used thirty-five monoclonal antibodies against SARS-CoV-2 to demonstrate how sequence-independent antibody identification can be achieved by simple means applied onto the protein. First, we examined the intact and light chain masses of the antibodies relative to the reference material NIST-mAb 8671. Already half of the antibodies could be identified based solely on these two parameters. In addition, we developed two complementary peptide mass fingerprinting methods with MALDI-TOF-MS that can be performed in 45 minutes and had a combined sequence coverage of over 80%. One method is based on the partial acidic hydrolysis of the protein by 5 mM of sulfuric acid at 99 °C. Furthermore, we established a fast way for a tryptic digest without an alkylation step. We were able to show that the distinction of clones is possible simply by a brief visual comparison of the mass spectra. In this work, two clones originating from the same immunization gave the same fingerprints. Later, a hybridoma sequencing confirmed the sequence identity of these sister clones. In order to automate the spectral comparison for larger libraries of antibodies, we developed the online software ABID 2.0 (https://gets.shinyapps.io/ABID/). This open-source software determines the number of matching peptides in the fingerprint spectra. We propose that publications and other documents critically relying on monoclonal antibodies with unknown amino acid sequences should include at least one antibody fingerprint. By fingerprinting an antibody in question, its identity can be confirmed by comparison with a library spectrum at any time and context.

Preprint ARTICLE | doi:10.20944/preprints202203.0155.v1

Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-Analysis

Kaiming Tao, Philip L. Tzou, Sergei L. Kosakovsky Pond, John P.A. Ioannidis, Robert W. Shafer

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; Omicron variant; Monoclonal antibody; Neutralization; Spike protein

Online: 10 March 2022 (14:30:25 CET)

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Preprint ARTICLE | doi:10.20944/preprints202203.0040.v1

Augmented Sensitivity of At-Home Rapid SARS-CoV-2 Antigen Test (RAT) Kits with Computer Vision

Kim Miikki, Lars Miikki, Jenny Wiklund, Alp Karakoç

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; rapid antigen test; RT-PCR test; COVID-19; image processing; Raspberry Pi

Online: 2 March 2022 (08:06:49 CET)

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Preprint ARTICLE | doi:10.20944/preprints202202.0273.v1

Minimum Alveolar Concentration of Isoflurane in Rats Chronically Treated with the Synthetic Cannabinoid WIN 55,212-2

José Antonio Ibancovichi, Julio Raul Chavez-Monteagudo, Pedro Sanchez-Aparicio, Sergio Recillas-Morales, Jorge Osorio-Avalos, Marco Antonio DePaz-Campos

Subject: Medicine And Pharmacology, Anesthesiology And Pain Medicine Keywords: MAC; Isoflurane; WIN 55,212-2; Rat

Online: 22 February 2022 (11:28:05 CET)

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Preprint BRIEF REPORT | doi:10.20944/preprints202201.0057.v1

Full Genome Analysis of Circulating DENV-2 in Senegal Reveals a Regional Diversification Into Separate Clades

Idrissa Dieng, Amadou Diallo, Mignane Ndiaye, Moussa Moise Diagne, Safietou Sankhe, Marie Henriette Ndione, Amadou Alpha Sall, Cheikh Loucoubar, Ousmane Faye, Oumar Faye

Subject: Biology And Life Sciences, Virology Keywords: Dengue virus; complete genome; Cosmopolitan genotype; Senegal; 2018; Regional diversification

Online: 6 January 2022 (09:56:19 CET)

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Preprint ARTICLE | doi:10.20944/preprints202107.0554.v1

Emergence of Unique SARS-CoV-2 ORF10 Variants and Their Impact on Protein Structure and Function

Sk. Sarif Hassan, Kenneth Lundstrom, Ángel Serrano-Aroca, Parise Adadi, Alaa Aljabali, Elrashdy Redwan, Amos Lal, Ramesh Kandimalla, Tarek El-Aziz, Pabitra Choudhury, Gajendra Azad, Samendra Sherchan, Murtaza Tambuwala, Gaurav Chauhan, Kazuo Takayama, Debmalya Barh, Giorgio Palù, Pallab Basu, Vladimir N Uversky

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; ORF10; Co-mutations; Intrinsic Protein Disorder; Ubiquitin Ligase Complex

Online: 26 July 2021 (09:07:38 CEST)

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Preprint DATASET | doi:10.20944/preprints202005.0345.v2

A Season Independent U-net Model for Robust Mapping of Solar Arrays Using Sentinel-2 Imagery

Michael Evans, Taylor Minich, Rachel Soobitsky, Kumar Mainali

Subject: Environmental And Earth Sciences, Atmospheric Science And Meteorology Keywords: computer vision; deep learning; Earth Engine; remote sensing; renewable energy; Tensorflow

Online: 21 July 2021 (14:53:14 CEST)

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Preprint REVIEW | doi:10.20944/preprints202107.0184.v1

Systematic Review of the Effects of a Dietary Education Intervention on Individuals with Type 2 Diabetes

Ju Ri Kim, Myung-haeng Hur

Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Diabetes mellitus; diet, education; systematic review.

Online: 8 July 2021 (09:57:01 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202106.0650.v1

Cellular and humoral immunogenicity of a candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1

Khalid A. Alluhaybi, Rahaf H. Alharbi, Rowa Y. Alhabbab, Najwa D Aljehani, Sawsan S. Alamri, Mohammad Basabrain, Rehaf Alharbi, Wesam H. Abdulaal, Mohamed A. Alfaleh, Levi Tamming, Wanyue Zhang, Mazen Hassanain, Abdullah Algaissi, Adel M. Abuzenadah, Xuguang Li, Anwar M Hashem

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2 vaccine; cellular and humoral immunogenicity; DNA vaccine

Online: 28 June 2021 (13:40:25 CEST)

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Working Paper ARTICLE

Retrieving Surface Soil Moisture over Wheat-Covered Areas Using Data from Sentinel-1 and Sentinel-2

Yan Li, Chengcai Zhang, Weidong Heng

Subject: Environmental And Earth Sciences, Atmospheric Science And Meteorology Keywords: Surface soil moisture; Sentinel-1 SAR; Sentinel-2; Vegetation water content; Water cloud model; Support vector regression

Online: 2 June 2021 (15:22:42 CEST)

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Preprint REVIEW | doi:10.20944/preprints202105.0264.v1

Applying Philosophy, Logic, and Rational Argumentation to the Severe Acute Respiratory Syndrome Coronavirus-2 Pandemic Response

Ari Joffe, David Redman

Subject: Social Sciences, Anthropology Keywords: COVID-19; critical scrutiny; logic; pandemic; response; SARS-CoV-2

Online: 12 May 2021 (10:48:05 CEST)

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Preprint REVIEW | doi:10.20944/preprints202104.0481.v1

Minimizing Errors in RT-PCR Detection and Quantification of SARS-CoV-2 RNA for Wastewater Surveillance

Warish Ahmed, Stuart Simpson, Paul Bertsch, Kyle Bibby, Aaron Bivins, Linda Blackall, Silvia Bofill-Mas, Albert Bosch, Joao Brandao, Phil Choi, Mark Ciesielski, Erica Donner, Nishita D'Souza, Andreas Farnleitner, Daniel Gerrity, Raul Gonzalez, John Griffith, Pradip Gyawali, Charles Haas, Kerry Hamilton, Chanditha Hapuarachchi, Valerie Harwood, Rehnuma Haque, Greg Jackson, Stuart Khan, Wesaal Khan, Masaaki Kitajima, Asja Korajkic, Giuseppina La Rosa, Blythe Layton, Erin Lipp, Sandra McLellan, Brian McMinn, Gertjan Medema, Suzanne Metcalfe, Wim Meijer, Jochen Mueller, Heather Murphy, Colleen Naughton, Rachel Noble, Sudhi Payyappat, Susan Petterson, Tarja Pitkanen, Veronica Rajal, Brandon Reyneke, Fernando Roman, Joan Rose, Marta Rusinol, Michael Sadowsky, Laura Sala-Comorera, Yin Xiang Setoh, Samendra Sherchan, Kwanrawee Sirikanchana, Wendy Smith, Joshua Steele, Rosalie Sabburg, Erin Symonds, Phong Thai, Kevin Thomas, Josh Tynan, Simon Toze, Janelle Thompson, Andy Whiteley, Judith Wong, Daisuke Sano, Stefan Wuertz, Irene Xagoraraki, Qian Zhang, Amity Zimmer-Faust, Orin Shanks

Subject: Environmental And Earth Sciences, Waste Management And Disposal Keywords: COVID-19; SARS-CoV-2; Wastewater; Surveillance; False-positive; False-negative; RT-PCR

Online: 19 April 2021 (13:08:13 CEST)

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Wastewater surveillance for pathogens using the reverse transcription-polymerase chain reaction (RT-PCR) is an effective, resource-efficient tool for gathering additional community-level public health information, including the incidence and/or prevalence and trends of coronavirus disease-19 (COVID-19). Surveillance of SARS-CoV-2 in wastewater may provide an early-warning signal of COVID-19 infections in a community. The capacity of the world’s environmental microbiology and virology laboratories for SARS-CoV-2 RNA characterization in wastewater is rapidly increasing. However, there are no standardized protocols nor harmonized quality assurance and quality control (QA/QC) procedures for SARS-CoV-2 wastewater surveillance. This paper is a technical review of factors that can lead to false-positive and -negative errors in the surveillance of SARS-CoV-2, culminating in recommendations and strategies that can be implemented to identify and mitigate these errors. Recommendations include, stringent QA/QC measures, representative sampling approaches, effective virus concentration and efficient RNA extraction, amplification inhibition assessment, inclusion of sample processing controls, and considerations for RT-PCR assay selection and data interpretation. Clear data interpretation guidelines (e.g., determination of positive and negative samples) are critical, particularly during a low incidence of SARS-CoV-2 in wastewater. Corrective and confirmatory actions must be in place for inconclusive and/or potentially significant results (e.g., initial onset or reemergence of COVID-19 in a community). It will also be prudent to perform inter-laboratory comparisons to ensure results are reliable and interpretable for ongoing and retrospective analyses. The strategies that are recommended in this review aim to improve SARS-CoV-2 characterization for wastewater surveillance applications. A silver lining of the COVID-19 pandemic is that the efficacy of wastewater surveillance was demonstrated during this global crisis. In the future, wastewater will play an important role in the surveillance of a range of other communicable diseases.

Preprint ARTICLE | doi:10.20944/preprints202103.0609.v1

Evaluation of a Bioaerosol Sampler for Indoor Environmental Surveillance of Severe Acute Respiratory Syndrome Coronavirus 2

Patrick F. Horve, Leslie Dietz, Dale Northcutt, Jason Stenson, Kevin G. Van Den Wymelenberg

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2; COVID-19; Aerosols; Environmental Surveillance; Air Sampling

Online: 24 March 2021 (17:29:23 CET)

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Working Paper ARTICLE

XEN Glaucoma Implant for Refractory Glaucoma Management: Results and Complications during a 2-year Follow-up

Katarzyna Lewczuk, Joanna Konopińska, Joanna Joablonska, Zofia Mariak, Marek Rękas

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: refractory glaucoma; XEN implant; management; retrospective study, MIGS, glaucoma surgery, bleb, subconjunctival stent

Online: 2 March 2021 (14:25:54 CET)

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Preprint REVIEW | doi:10.20944/preprints202102.0432.v1

Biomedical Research During the COVID-19 Pandemic: Success in Sars-Cov-2 and Other Infectious Diseases

Nuno S. Osório, Maria Isabel Veiga

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; SARS-CoV-2; Infectious disease; Pandemics; Epidemics; Biomedical Research

Online: 19 February 2021 (10:03:47 CET)

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Preprint ARTICLE | doi:10.20944/preprints202101.0473.v1

Summarize of the Available Molecular Methods for Detection of Sars-Cov-2 During the Ongoing Pandemic

Fabio Arena, Simona Pollini, Gian Maria Rossolini, Maurizio Margaglione

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: molecular methods; virus; pandemic; Coronaviridae; COVID-19, diagnosis; UK variant; B.1.1.7 variant; 501Y.V2 variant

Online: 25 January 2021 (10:32:38 CET)

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Working Paper REVIEW

A Critical Review of Disinfection Processes to Control SARS-CoV-2 Transmission in the Food Industry

Adrián Pedreira, Yeşim Taşkın, Míriam R. García

Subject: Biology And Life Sciences, Food Science And Technology Keywords: SARS-CoV-2; COVID-19 pandemic; food industry; disinfection trade-offs; one-health

Online: 15 December 2020 (12:58:18 CET)

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Preprint BRIEF REPORT | doi:10.20944/preprints202010.0308.v1

Potential Role of Children in the Household Transmission of SARS-CoV-2 Infection in Catalonia (Spain)

Antoni Soriano-Arandes, Berta Ferran, Magda Campins, Juliana Esperalba-Esquerra, Juliana Reyes-Urueña, Uxue Lazcano, Anna Gatell, Pepe Serrano, Xavier Bruna, Ramon Capdevila, Maria Esteller, Andres Anton, Jordi Gómez i Prat, Gloria Ruiz, Anna Fàbrega, Neus Rius, Marina Fenoy, Núria López, Almudena Sánchez, Miriam Poblet, Anton Foguet, Guillermo García, Teresa Riera, Elisenda Martínez-Carbonell, Yesika Díaz, Valentí Pineda, Pere Soler-Palacin

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2; COVID-19; children; household; contact tracing

Online: 14 October 2020 (13:33:49 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202009.0666.v1

An SU(4)/SU(2) Model as an Effort to Understand QCD, Confinement and Asymptotic Freedom

Dimitris Mastoridis, K. Kalogirou

Subject: Computer Science And Mathematics, Applied Mathematics Keywords: qcd; confinement; asymptotic freedom; standard model; coset; Stiefel manifolds

Online: 27 September 2020 (07:39:43 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202009.0345.v1

ACEII Gene Analysis Exposes SARS-CoV-2 As A Potential Threat to Agricultural and National Security

Michael Ruhl, Tracie Jenkins

Subject: Biology And Life Sciences, Agricultural Science And Agronomy Keywords: food safety; SARS-CoV-2; coronavirus; ACEII; agricultural security; national security

Online: 16 September 2020 (03:57:36 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202008.0293.v1

PhotonLabeler: An Inter-disciplinary Platform for Visual Interpretation and Labeling of ICESat-2 Geolocated Photon Data

Lonesome Malambo, Sorin C. Popescu

Subject: Environmental And Earth Sciences, Remote Sensing Keywords: ICESat-2; photon-counting lidar; photon labeling; visualization; ATL03; ATL08; visual interpretation; solar-induced noise

Online: 13 August 2020 (08:08:40 CEST)

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Preprint REVIEW | doi:10.20944/preprints202008.0065.v1

SARS-CoV-2 A Relation with Other Acute Respiratory Tract Infectious (ARTI) Diseases: A Short Communication

HAKANI SYMPLI

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: SARS-CoV-2; SARS-CoV; influenza; pneumonia; respiratory tract infectious diseases

Online: 3 August 2020 (08:44:56 CEST)

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Preprint REVIEW | doi:10.20944/preprints202007.0724.v1

An SU(2) Gauge Principle for the CMB: Perspectives on Dark Sector of the Cosmological Model

Ralf Hofmann

Subject: Physical Sciences, Mathematical Physics Keywords: light scalar fields; axial anomaly; SU(2) Yang-Mills thermodynamics; de-percolation of axionic lumps; cosmological and galactic dark-matter densities

Online: 30 July 2020 (12:35:00 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202007.0381.v1

Estimating Fractional Snow Cover in Open Terrain from Sentinel-2 Using the Normalized Difference Snow Index

Simon Gascoin, Zacharie Barrou Dumont, César Deschamps-Berger, Florence Marti, Germain Salgues, Juan Ignacio López-Moreno, Jesús Revuelto, Timothée Michon, Paul Schattan, Olivier Hagolle

Subject: Environmental And Earth Sciences, Environmental Science Keywords: snow; snow cover area; fractional snow cover; Sentine-2

Online: 17 July 2020 (14:05:06 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202007.0144.v1

Molecular Tracing of SARS-CoV-2 in Italy in the First Three Months of the Epidemic

Alessia Lai, Annalisa Bergna, Sara Caucci, Nicola Clementi, Ilaria Vicenti, Filippo Dragoni, Anna Maria Cattelan, Stefano Menzo, Angelo Pan, Annapaola Callegaro, Adriano Tagliabracci, Arnaldo Caruso, Francesca Caccuri, Silvia Ronchiadin, Claudia Balotta, Maurizio Zazzi, Emanuela Vaccher, Massimo Clementi, Massimo Galli, Gianguglielmo Zehender

Subject: Biology And Life Sciences, Virology Keywords: phylodynamic analyses; SARS-CoV2 circulation in Italy; molecular tracing; Whole Genome Sequencing

Online: 8 July 2020 (11:00:19 CEST)

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Preprint REVIEW | doi:10.20944/preprints202006.0086.v2

An Overview of Basic Molecular Biology of SARS-CoV-2 and Current COVID-19 Prevention Strategies

Ankur Das, Raja Ahmed, Suraiya Akhtar, Khaleda Begum, Sofia Banu

Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; Genome organisation and expression; Polyproteins; Prevention strategies

Online: 14 June 2020 (16:49:10 CEST)

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Preprint REVIEW | doi:10.20944/preprints202005.0376.v1

Computational Strategies to Combat COVID-19: Useful Tools to Accelerate SARS-CoV-2 and Coronavirus Research

Franziska Hufsky, Kevin Lamkiewicz, Alexandre Almeida, Abdel Aouacheria, Cecilia Arighi, Alex Bateman, Jan Baumbach, Niko Beerenwinkel, Christian Brandt, Marco Cacciabue, Sara Chuguransky, Oliver Drechsel, Robert D. Finn, Adrian Fritz, Stephan Fuchs, Georges Hattab, Anne-Christin Hauschild, Dominik Heider, Marie Hoffmann, Martin Hölzer, Stefan Hoops, Lars Kaderali, Ioanna Kalvari, Max von Kleist, René Kmiecinski, Denise Kühnert, Gorka Lasso, Pieter Libin, Markus List, Hannah F. Löchel, Maria J. Martin, Roman Martin, Julian Matschinske, Alice C. McHardy, Pedro Mendes, Jaina Mistry, Vincent Navratil, Eric Nawrocki, Áine Niamh O'Toole, Nancy Palacios-Ontiveros, Anton I. Petrov, Guillermo Rangel-Piñeros, Nicole Redaschi, Susanne Reimering, Knut Reinert, Alejandro Reyes, Lorna Richardson, David L. Robertson, Sepideh Sadegh, Joshua B. Singer, Kristof Theys, Chris Upton, Marius Welzel, Lowri Williams, Manja Marz

Subject: Biology And Life Sciences, Virology Keywords: virus bioinformatics; SARS-CoV-2; sequencing; epidemiology; drug design; tools

Online: 23 May 2020 (11:01:11 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0343.v1

Community Research Amid COVID-19 Pandemic: Genomics Analysis of SARS-CoV-2 over Public GALAXY server

Ambarish Kumar, Ali Haider Bangash, Bjoern Gruening

Subject: Biology And Life Sciences, Virology Keywords: GALAXY; Assembly; Annotation; Genomic Variants Discovery; Workflow

Online: 21 May 2020 (09:57:42 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202005.0341.v1

Role of Advanced Glycation End Products on Aortic Calcification in Patients with Type 2 Diabetes Mellitus

Pilar Sanchis, Rosmeri Rivera, Regina Fortuny, Carlos Rio, Miguel Mas-Gelabert, Marta Gonzalez-Freire, Felix Grases, Luis Masmiquel

Subject: Biology And Life Sciences, Endocrinology And Metabolism Keywords: AGEs; aortic calcification; type 2 diabetes mellitus; diabetes-related complications

Online: 21 May 2020 (09:46:56 CEST)

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Working Paper BRIEF REPORT

Identification of Novel Missense Mutations in a Large Number of Recent SARS-CoV-2 Genome Sequences

Hugh Y. Cai, Kimberly K. Cai, Julang Li

Subject: Biology And Life Sciences, Virology Keywords: COVI-19; SARS-CoV-2; virus; mutation; polymorphism; genome sequence

Online: 21 May 2020 (04:09:53 CEST)

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Background: SARS-CoV-2 infection has spread to over 200 countries since it was first reported in December of 2019. Significant country-specific variations in infection and mortality rate have been noted. Although country-specific differences in public health response have had a large impact on infection rate control, it is currently unclear as to whether evolution of the virus itself has also contributed to variations in infection and mortality rate. Previous studies on SARS-CoV-2 mutations were based on the analysis of ~ 160 SARS-CoV-2 sequences available until mid-February 2020.^{2, 3, 4, 5} By mid-April, > 550 SARS-CoV-2 sequences had been deposited in GenBank, and over 8,200 in the GISAID database. Methods: We performed a sequence analysis on 474 SARS-CoV-2 genomes submitted to GenBank up to April 11, 2020 by multiple alignment using Map to a Reference Assembly and Variants/SNP identification. The results were verified on a larger scale, 8,126 hCoV-19 (SARS-CoV-2) sequences from GISAID database. Results: We identified 5 recently emerged mutations in many isolates (up to 40%). Our analysis highlights 5 frequent new mutations that have emerged since late February 2020. These mutations are: one each missense (non-synonymous) mutation in orf1ab (C1059T), orf3 (G25563T) and orf8 (C27964T), one in 5’UTR (C241T), one in a non-coding region (G29553A). The final mutation (G29553A) was found to be almost exclusive to the US isolates. The first 3 mutations are non-synonymous, leading to amino acid substitutions in the viral protein sequence. Except for C241T, all the novel mutations identified are absent in the isolates from Italy and Spain in the SARS-CoV-2 genomes deposited in GenBank and GISAID by April 13, 2020. Conclusion: The results of current study indicate that new mutations are emerging as COVID-19 pandemic are spreading to different countries and that geography specific mutants may exist. The findings of current study lay the foundation for further investigation into the impact of SARS-CoV-2 mutations on disease incidence, severity, and host immune response. In addition, it may also provide insights into vaccine development and serological response detection for the virus.

Preprint ARTICLE | doi:10.20944/preprints202005.0333.v1

An In Silico Analysis of Potential SARS-CoV-2 Interactions with Proteins Involved in Placental Functions

Ashikh A. Seethy, Sunil Singh, Indrani Mukherjee, Karthikeyan Pethusamy, Kakali Purkayastha, Jai Bhagwan Sharma, Ruby Dhar, Subhradip Karmakar

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV-2; COVID-19; pregnancy; trophoblasts; interactome; placenta

Online: 21 May 2020 (03:38:05 CEST)

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COVID-19 is a rapidly evolving medical emergency that has drawn global attention, unprecedented in any disease of its kind in recent times. The magnitude of the health crisis emerging from this pandemic has overwhelmed health care workers worldwide and called in for extraordinary measures to contain this virus. A simple Pubmed query on “COVID-19” returned with 12214 articles (as on May 17^th, 2020), published just within a few months. A detailed survey revealed around 250 clinical reports, 8 clinical trials, 9 meta-analyses, and 906 reviews that were published during this time span. Combining the strings “COVID-19 and Pregnancy” yielded a total of 132 reports while querying “COVID-19 and Placenta” returned with just 11 articles Even taking into considerations that few materials are in the PrePrint Server, we still have a gross under-representation of studies addressing the effect of this disease on pregnancy outcome and maternal & child health. An essential aspect of a successful pregnancy is proper placentation, where transiently invasive placental trophoblast cells invade the maternal endometrium to establish a functional feto-maternal communication. Based on the elegant study by David. E. Gordon, et al. published in Nature (April 30, 2020), which identified 332 human host proteins interacting with SARS-nCoV2 using an affinity-based purification, we interrogated several gene expression data sets available at NCBI-GEO related to trophoblast invasion and differentiation. Both of these processes are indispensable for placentation and fetal survival. Our analysis showed several overlaps with the interactome proteins implying that SARS-CoV-2 infection can affect several proteins, which are crucial for trophoblasts function. GeneMANIA and STRING based functional analysis further revealed that several of that SARS-CoV-2 interacting trophoblast proteins as a hub for the protein-protein interaction network. Our study thus elucidates the possible effect of SARS-CoV-2 infection on placenta formation and pregnancy outcome.

Preprint REVIEW | doi:10.20944/preprints202005.0178.v1

SARS-CoV-2 and the Possible Connection to ERs, ACE2 and RAGE: Focus on Susceptibility Factors

Roberta Sessa Stilhano, Angelica Jardim Costa, Michelle Sayuri Nishino, Shahin Shams, Cynthia Silva Bartolomeo, Ana Cristina Breithaupt-Faloppa, Eduardo Alexandre Silva, Ana Lopez Ramirez, Carla Maximo Prado, Rodrigo Portes Ureshino

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; estrogen; RAGE; ACE2

Online: 10 May 2020 (17:46:13 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0510.v1

A Structural View at SARS-CoV-2 RNA Replication Machinery: RNA Synthesis, Proofreading and Final Capping

Maria Romano, Alessia Ruggiero, Flavia Squeglia, Giovanni Maga, Rita Berisio

Subject: Biology And Life Sciences, Biophysics Keywords: SARS-CoV-2; COVID19; RNA replication; protein structure; infectious disease

Online: 29 April 2020 (12:52:18 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0439.v1

Highly Conserved Homotrimer Cavity Formed by the SARS-CoV-2 Spike Glycoprotein: A Novel Binding Site

Umesh Kalathiya, Monikaben Padariya, Marcos Mayordomo, Małgorzata Lisowska, Judith Nicholson, Ashita Singh, Maciej Baginski, Robin Fåhraeus, Neil Carragher, Kathryn Ball, Juergen Haas, Alison Daniels, Ted R. Hupp, Javier Antonio Alfaro

Subject: Biology And Life Sciences, Biophysics Keywords: SARS-CoV-2; COVID-19; spike glycoprotein; variability; molecular docking; molecular dynamics; inhibitors

Online: 24 April 2020 (11:42:01 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202004.0425.v1

Non-Coding RNAs and Innovative Therapeutic Strategies to Target the 5’UTR of SARS-CoV-2

Antonella Baldassarre, Alessandro Paolini, Stefania Paola Bruno, Cristina Felli, Alberto Eugenio Tozzi, Andrea Masotti

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: SARS-CoV-2; COVID-19; 5’UTR; miRNAs; RNAi; GapmeRs

Online: 24 April 2020 (04:16:20 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0377.v1

The Dynamics of Humoral Immune Responses Following SARS-CoV-2 Infection and the Potential for Reinfection

Paul Kellam, Wendy Barclay

Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; immune response; antibodies

Online: 21 April 2020 (06:56:12 CEST)

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Preprint REVIEW | doi:10.20944/preprints202004.0087.v1

While We Wait for a Vaccine Against SARS-CoV-2, Why Not Think About Available Drugs?

Francisco J. Barrantes

Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Coronavirus; COVID-19; SARS-CoV-2; design drugs; ACE2; prophylaxis

Online: 7 April 2020 (11:02:13 CEST)

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At the time of reception of this article (April 2, 2020), efforts to develop a specific vaccine against SARS-Cov-2, the causative agent of the coronavirus disease 2019 (COVID-19), had just begun trial phase 1, but full validation of this and other current developments is likely to take many more months to reach completion. The ongoing pandemic constitutes a major health burden of world proportions that is also having a devastating impact on whole economies worldwide, the knock-on effects of which could be catastrophic especially in poorer countries. Alternative measures to ameliorate the impact and hamper or minimally slow down disease progression are urgently called for. This review discusses past and currently evolving data on the etiological agent of the current pandemic, SARS-CoV-2, and its host cell receptors with a view to disclosing alternative drugs for palliative or therapeutic approaches. Firstly, SARS-CoV-2 exhibits marked tropism for cells that harbor the membrane-bound metalloprotease angiotensin-converting enzyme 2 (ACE2) at their plasmalemma, predominantly in cells lining the oral cavity, upper respiratory tract, and bronchoalveolar cells, making these epithelial mucosae the most likely viral receptor cell targets and entry routes. Secondly, the crystal structures of several coronavirus spike proteins in complex with their cell host target receptors, and of SARS-Cov-2 in complex with an inhibitor, are now available at atomic resolution through X-ray diffraction and cryo-electron microscopy studies. Thirdly, viral entry of other viruses has been successfully blocked by inhibiting viral endogenous proteases or clathrin/dynamin-dependent endocytosis, the same internalization pathway followed by ACE2 and some viruses. Fourthly, the target cell-surface receptor molecules and SARS-CoV-2 possess other putative sites for drugs potentially modulating receptor activity or virus processing. A multi-pronged pharmacological approach attacking more than one flank of the viral-receptor interactions is worth considering as a front-line strategy.

Preprint COMMUNICATION | doi:10.20944/preprints202003.0395.v2

Beclabuvir can Inhibit the RNA-dependent RNA Polymerase of Newly Emerged Novel Coronavirus (SARS-CoV-2)

Kunal Dutta, Sergey Shityakov, Olga Morozova, Ibrahim Khalifa, Jin Zhang, Wei Zhu, Amiya Panda

Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Novel coronavirus (SARS-CoV-2); RdRp; HCV; beclabuvir; in silico; molecular docking

Online: 2 April 2020 (11:25:57 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202003.0428.v1

A Furin Cleavage Site Inserted into the Spike Protein of SARS-CoV-2: A Structural Implication?

Wei Li

Subject: Biology And Life Sciences, Biophysics Keywords: COVID-19; SARS-CoV-2; furin cleavage site (FCS); salt bridging analysis

Online: 29 March 2020 (08:54:42 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202003.0236.v1

Improved Rapid Visual Earthquake Hazard Safety Evaluation of Existing Buildings Using Type-2 Fuzzy Logic Model

Ehsan Harirchian, Tom Lahmer

Subject: Engineering, Civil Engineering Keywords: seismic vulnerability; fuzzy logic system; Interval Type-2 Fuzzy logic; retrofit prioritization; damage category classification

Online: 15 March 2020 (01:54:35 CET)

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Preprint ARTICLE | doi:10.20944/preprints202002.0308.v1

Pharmacoinformatics and Molecular Dynamic Simulation Studies Reveal Potential Inhibitors of SARS-CoV-2 Main Protease 3CL^pro

Mubarak A. Alamri, Muhammad Tahir ul Qamar, Safar M. Alqahtani

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: SARS-CoV-2; COVID-19; 3CL protease; molecular docking; molecular dynamics and simulations

Online: 23 February 2020 (02:17:46 CET)

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Preprint ARTICLE | doi:10.20944/preprints201808.0464.v1

Post-partum Depression in Mothers of Children under 2 years in Military Barracks in Lagos, Nigeria

Alero Ann Roberts, Chisa Mariam Nworka, Esther Oluwakemi Oluwole, Ezekiel Sofela Oridota

Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: Postpartum depression, Edinburgh Postpartum Depression Scale, general help-seeking, mothers, military barracks

Online: 27 August 2018 (14:59:46 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201705.0053.v2

Vibration Control Design for a Plate Structure with Electrorheological ATVA Using Interval Type-2 Fuzzy System

Chih-Jer Lin, Chun-Ying Lee, Ying Liu

Subject: Engineering, Mechanical Engineering Keywords: Electro-Rheological fluid; Semi-active vibration control; tunable vibration absorber; type-1 fuzzy control; interval type-2 fuzzy control

Online: 23 May 2017 (15:58:35 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202402.1587.v1

Endoscopic Papillary Balloon Dilation for Children with Common Bile Duct Stones, Especially for Infants: A Literature Review

Katsunori Kouchi, Ayako Takenouchi, Aki Matsuoka, Kiyoaki Yabe, Hiroko Yoshizawa, Chikako Nakata, Jun Fujishiro, Harutoshi Sugiyama

Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: endoscopic papillary balloon dilation, common bile duct stone, choledocholithiasis, children, endoscopic retrograde cholangiopancreatography

Online: 28 February 2024 (08:48:37 CET)

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Background: Endoscopic sphincterotomy (EST) has been employed for the endoscopic treatment of common bile duct stones (CBDSs), and a high success rate of stone removal has been reported. However, EST is associated with the risk of bleeding, perforation, and sphincter of Oddi function disruption. To avoid these risks, endoscopic papillary balloon dilation (EPBD) is an option for CBDS. Sphincter of Oddi function preservation decreases long-term biliary infection and gallstone recurrence. EPBD may have advantages in children who require a long follow-up. However, there have been few reports on pediatric cases, particularly in infants. Methods: From September 2017 to December 2023, we performed EPBD for four pediatric CBDSs. The patients were aged from 5 months to 8 years; including two infants aged 5 and 6 months. Furthermore, we reviewed the stone removal rate and complications of 545 ESTs performed at high-volume centers and 13 EPBD-reported cases in children with CBDSs. Results: CBDSs of all patients who underwent EPBD in our institution were successfully removed. No bleeding or perforation was noted, and pancreatitis was observed in three patients. In an analysis of 545 ESTs in children, the stone removal rate was high, ranging from 83% to 100% (mean, 96%). The incidence of pancreatitis was 0%–9.6% (mean, 4.4%), and the grade of pancreatitis was almost mild. The bleeding frequency was 1.3%–5.4% (mean, 2.7%). According to the grade of bleeding, seven and four cases were mild (64%) and moderate (36%), respectively, Compared with adult cases who underwent EST, the frequency of pancreatitis and bleeding was almost similar in children.; however once bleeding occur, it has a higher risk of leading to blood transfusion in children. Stone removal by EPBD in children was 100% successful. All complications were pancreatitis, and its frequency was 46% (6/13 patients, including five mild cases and one moderate case), which is higher than that of EST and adult cases who underwent EPBD. In most children with pancreatitis, pancreatic enzyme levels returned to normal within 2–3 days following EPBD, and no severe cases caused by EPBD were reported. Conclusions: CBDS removal by EPBD in children has a high success rate with very low risk of bleeding and perforation. Although pancreatitis frequently occurs, most cases are mild. Sphincter of Oddi function preservation by EPBD is expected to prevent long-term stone recurrence and biliary tract infection, and EPBD is considered an effective method for CBDS removal in children.

Preprint ARTICLE | doi:10.20944/preprints202006.0204.v1

High Concentrations of Presepsin in the Bile and Its Marked Elevation in Biliary Tract Diseases: A Retrospective Analysis

Takashi Yamaguchi, Masahiro Ohira, Naoyuki Kawagoe, Shoko Nakamura, Shou Tanaka, Rena Oka, Yasuhiro Watanabe, Yuta Sato, Atsuhito Saiki, Yasuo Matsuzawa, Hideaki Bujo, Kensuke Terai, Nobuyuki Hiruta, Ichiro Tatsuno, Chiaki Nakaseko, Hidemasa Kikuchi, Katsuyoshi Matsuoka, Hiromitsu Yokota, Naomi Shimizu

Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: Presepsin; Sepsis; Sequential Organ Failure Assessment (SOFA) score; alkaline phosphatase (ALP); Bile

Online: 16 June 2020 (09:43:45 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201907.0075.v1

Objective Response by mRECIST is an Independent Prognostic Factor for overall Survival in Hepatocellular Carcinoma in SILIUS Trial

Masatoshi Kudo, Kazuomi Ueshima, Yasutaka Chiba, Sadahisa Ogasawara, Shuntaro Obi, Namiki Izumi, Hiroshi Aikata, Hiroaki Nagano, Etsuro Hatano, Yutaka Sasaki, Keisuke Hino, Takashi Kumada, Kazuhide Yamamoto, Yasuharu Imai, Shouta Iwadou, Chikara Ogawa, Takuji Okusaka, Fumihiko Kanai, Yasuaki Arai

Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: hepatocellular carcinoma; objective response; modified RECIST; sorafenib; hepatic arterial infusion chemotherapy

Online: 4 July 2019 (10:56:53 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201906.0285.v1

Lenvatinib as an Initial Treatment in Patients with Intermediate-stage Hepatocellular Carcinoma Beyond up-to-seven Criteria and Child-Pugh A Liver Function: A Proof-of-Concept Study

Masatoshi Kudo, Kazuomi Ueshima, Stephan Chan, Tomohiro Minami, Hirokazu Chishina, Tomoko Aoki, Masahiro Takita, Satoru Hagiwara, Yasunori Minami, Hiroshi Ida, Mamoru Takenaka, Toshiharu Sakurai, Tomohiro Watanabe, Masahiro Morita, Chikara Ogawa, Yoshiyuki Wada, Masafumi Ikeda, Hiroshi Ishii, Namiki Izumi, Naoshi Nishida

Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: hepatocellular carcinoma; lenvatinib; transcatheter arterial chemoembolisation; intermediate stage; up-to-seven criteria

Online: 27 June 2019 (08:13:58 CEST)

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Background: Although transcatheter arterial chemoembolisation (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients currently remains an unmet need in clinical practice. Here, we performed a proof-of-concept study that lenvatinib may be more favourable treatment option over TACE as an initial treatment in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-seven criteria. Methods: This proof-of-concept study included 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria [unresectable, beyond the up-to-seven criteria, no prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child-Pugh A liver function] were selected for the study. Propensity score matching was used to adjust for patient demographics. Results: After propensity-score matching, outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials, 1 in early access program and 15 in real world setting) and 60 patients treated with cTACE as the initial treatment was compared. The change of ALBI score from baseline to the end of treatment were -2.61 to -2.61 for 30 patients in lenvatinib group (p = 0.254) and -2.66 to -2.09 in cTACE group (p < 0.01), respectively. The lenvatinib group showed a significantly higher objective response rate (73.3% vs. 33.3%; p < 0.001) and significantly longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p < 0.001). Overall survival was significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p < 0.01). Conclusion: In patients with large or multinodular intermediate-stage HCC exceeding the up-to-seven criteria with Child-Pugh A liver function, who usually do not benefit from TACE, lenvatinib provides more favorable outcome than TACE.

Preprint ARTICLE | doi:10.20944/preprints202408.1093.v1

Prognostic Impact of Statins in Heart Failure with Preserved Ejection Fraction

Samanta Ortega-Hernández, Sonia González-Sosa, Alicia Conde Martel, Joan Carles Trullàs, Pau Llàcer, José Pérez-Silvestre, José Carlos Arévalo-Lorido, Jesús Casado-Cerrada, Francesc Formiga, Luis Manzano, Noel Lorenzo Villalba, Manuel Montero-Pérez-Barquero

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Heart Failure; Preserved Ejection Fraction; Mortality; Statins

Online: 14 August 2024 (17:01:08 CEST)

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Preprint REVIEW | doi:10.20944/preprints202404.1054.v1

Genetics and Molecular Mechanisms of Idiopathic Dilated Cardiomyopathy, a Possible Guide to Individualized Management

Diana-Aurora Arnautu, Octavian-Marius Cretu, Daniel Florin Lighezan, Minodora Andor, Ioana Citu, Dragoș Cozma, Brenda-Cristiana Bernad, Adrian-Pavel Trifa, Diana Lighezan, Elena-Silvia Bernad, Dragos Catalin Jianu, Cristian Oancea, Ioan-Radu Lala, Sergiu-Florin Arnautu, Mirela-Cleopatra Tomescu

Subject: Biology And Life Sciences, Life Sciences Keywords: dilated cardiomyopathy; genetics; heart failure; genotype - specific therapy

Online: 16 April 2024 (15:53:28 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202402.1615.v1

Novel Biomarkers in Evaluating Cardiac Function in Patients on Hemodialysis – a Pilot Prospective Observational Cohort Study

Lazar A. Chisavu, Viviana M. Ivan, Adelina Mihaescu, Flavia Chisavu, Oana Schiller, Luciana Marc, Flaviu Bob, Adalbert Schiller

Subject: Medicine And Pharmacology, Internal Medicine Keywords: hemodialysis; mortality; cardio-vascular disease; novel biomarkers; cardiac function and structure

Online: 28 February 2024 (13:52:38 CET)

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Preprint ARTICLE | doi:10.20944/preprints202408.0285.v1

Latent Bacterial Cells Residing Inside Macrophages Can Be Spotted With pH-sensitive Fluorescent FRET Probe in Polymeric Micellar Formulation

Igor D. Zlotnikov, Alexander A. Ezhov, Natalya G. Belogurova, Elena V. Kudryashova

Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: theranostics; FRET marker; pH sensitivity; bacterial infections; visualization; macrophage

Online: 6 August 2024 (02:58:24 CEST)

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As shown previously, Rhodamine 6G (R6G) and 4-nitro-2,1,3-benzoxadiazole (NBD) linked through a spacer molecule spermidine (spd), R6G-spd-NBD, produce a fluorescent probe with pH-sensitive FRET effect, that can be useful in a variety of diagnostic applications. Specifically, cancer cells can be spotted due to a local decrease in pH (Warburg effect). Here we extend this approach to infectious diseases – namely, leishmaniasis, brucellosis, and tuberculosis, are difficult to treat largely because of their localization inside macrophages. R6G-spd-NBD offers an opportunity to detect such bacteria and potentially deliver therapeutic target to treat them. The micellar form of the R6G-spd-NBD probe (chitosan or heparin grafted with lipoic acid residues, Chit-LA and Hep-LA, respectively) was obtained to improve the pH sensitivity in the desired range (5.5–7.5) and enable the selective targeting of bacterial cells, thus improving CLSM imaging. According to AFM (atomic force microscopy) data, the micelles containing NBD-spd-R6G have a compact and highly spherical shape, with a diameter ranging from 70 to 110 nm. The micellar form of the R6G-spd-NBD further improves absorption and penetration into bacteria, including those located inside macrophages. Due to negative charge of the surface, bacteria absorb positively charged R6G-spd-NBD, and even more so in the micellar form, when chitosan derivatives are used to form the polymeric micelle. Additionally, macrophages’ lysosomes can be easily distinguished due to their acidic pH. Confocal laser scanning microscopy was used to visualize samples of macrophages cells containing absorbed bacteria. The micellar formulation showed a significant selectivity to model E. coli vs Lactobacillus bacterial cells, and R6G-spd-NBD, being a mild bactericide, clears over 50% E.coli in conditions where Lactobacillus remains almost unaffected. Taken together, our data indicates that R6G-spd-NBD, as well as similar compounds, can have value not only for diagnostic, but also for theranostic applications.

Preprint REVIEW | doi:10.20944/preprints202407.1678.v1

Physiological and Molecular Mechanisms of Rice Tolerance to Salt and Drought Stress: Advances and Future Directions

Qingyang Li, Peiwen Zhu, Xinqiao Yu, Guolan Liu, Junying Xu

Subject: Biology And Life Sciences, Agricultural Science And Agronomy Keywords: salt and drought stress; physiological and molecular mechanisms; transcription factors; gene editing; multi-omics; smart agriculture

Online: 22 July 2024 (07:08:46 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202407.1228.v1

Optimising Disaster Resilience Through Advanced Risk Management and Financial Analysis of Critical Infrastructure in the Serbian Defence Industry

Nikola Vidović, Hatidža Beriša, Vladimir M. Cvetković

Subject: Social Sciences, Safety Research Keywords: disaster risk management; resilience; risk management; financial analysis; critical infrastructure; security; defence; Serbia

Online: 16 July 2024 (10:47:31 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202407.1095.v1

Impact of Image Size and Image Overlap on the Prediction Performance of Convolutional Neural Networks Trained for Road Classification

Calimanut-Ionut Cira, Miguel Angel Manso Callejo, Naoto Yokota, Tudor Sălăgean, Ana-Cornelia Badea

Subject: Environmental And Earth Sciences, Remote Sensing Keywords: road classification; aerial orthoimagery; deep learning; image size; image overlap; convolutional neural networks; statistical performance evaluation

Online: 14 July 2024 (03:11:57 CEST)

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Popular geo-computer vision works make use of aerial imager with sizes ranging from 64 × 64 to 1024 × 1024 pixels without any overlap, although the learning process of deep learning models can be affected by the reduced semantic context or the lack of information near image boundaries. In this work, the impact of three image sizes (256 × 256, 512 × 512, and 1024 × 1024 pixels) and two image overlap levels (no overlap and 12.5% overlap) on the performance of road classification models was statistically evaluated. For this, two convolutional neural networks used in various tasks of geospatial object extraction were trained (using the same hyperparameters) on a large dataset (containing aerial image data covering 8650 km² of the Spanish territory that was labelled with binary road information) under twelve different scenarios, each scenario featuring a different combination of tile size and overlap. To assess their generalisation capacity, the performance of all resulting models was evaluated on a data from novel areas covering approximately 825 km². The performance metrics obtained were analysed using appropriate descriptive and inferential statistical techniques to evaluate the impact of the performance at distinct levels of the fixed factors (tile size, tile overlap, neural network architecture). Statistical tests were applied to study the main and interaction effects of the fixed factors on the performance. A significance level of 0.05 was applied to all the null hypothesis tests. The results were highly significant for the main effects (p-values lower than 0.001), while the two-way and three-way interaction effects among them had different levels of significance. The results indicate that the training of road classification models on images with a higher tile size (more semantic context) and tile overlap (additional border context and continuity) significantly impacts their performance. The best model was trained on a dataset featuring tiles with a size of 1024 × 1024 pixels and a 12.5% overlap and achieved a loss value of 0.0984, an F1 score of 0.8728, and an ROC-AUC score of 0.9766, together with an error rate of 3.5% on the test set.

Preprint ARTICLE | doi:10.20944/preprints202407.0878.v1

Gustatory-Visual Interaction in Human Brain Cortex: fNIRS Study

Karolina Jezierska, Aneta Cymbaluk-Płoska, Justyna Zaleska, Wojciech Podraza

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: fNIRS; taste stimulation; human brain cortex; gustatory-visual interaction

Online: 11 July 2024 (10:00:50 CEST)

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Background: many studies, on for example taste-visual dissonance, have shown that the influence of the visual cortex on taste sensation is enormous. The aim of the presented work is to investigate, using fNIRS, whether a taste stimulus, in this case the taste of bitter, also causes stimulation of the visual cortex in fNIR study. Methods: 51 participants (204 examinations, 9 996 records) were examined with fNIRS, which collects signals from whole left hemisphere. Differences between the maximum and minimum changes in oxyHb concentrations (ΔoxyHb) for the areas of the brain cortex considered responsible for recording visual and gustatory signals were analyzed. Protocol I, II, III and IV – activation with distillate water, coffee with lower concentration, reference (no stimulation) and coffee with higher concentration respectively, were used. Results: We recorded high signals for teste activation on channels covered gustatory cortex, which confirms the correctness of the choice of research method. What seems important, and somewhat surprising, is the fact that we also received high signals for the channels 45-49, which cover the visual cortex. The statistical analysis does not show any statistical differences between the protocols I, II and IV (different taste activation – water, coffee A and coffee B) for specific channels. As a results of the analysis of the correlation between the subjective bitterness assessment solutions, and the signal ΔoxyHb height, it was observed that statically important correlation, although weak, occurs only for 14 and gustatory channels, only for coffee with a higher concentration. Additionally we recorded the only statistically significant difference between women and men for protocol I (water), where the ΔoxyHb signal was twice as high for women. Conclusions: In conclusion, we can clearly state that the senses of sight and taste work closely together. Moreover, this cooperation is not one-sided - not only the visual activation affects the perception of taste, but interestingly, the taste stimulus can generate a hemodynamic response - activity in the visual cortex.

Preprint ARTICLE | doi:10.20944/preprints202407.0203.v1

Projections on the Spatiotemporal Bioclimatic Change over the Phytogeographical Regions of Greece by the Emberger Index

Ioannis Charalampopoulos, Fotoula Droulia, Ioannis P. Kokkoris, Panayotis Dimopoulos

Subject: Environmental And Earth Sciences, Atmospheric Science And Meteorology Keywords: climate change; climate projections; aridisation; bioclimate classification; Southern Europe; Greece; natural capital management

Online: 2 July 2024 (10:00:41 CEST)

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Preprint REVIEW | doi:10.20944/preprints202405.1794.v1

Macrophages as a Source and Target of GDF-15

Lina Susana Silva Bermudez, Harald Klüter, Julia Kzhyshkowska

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: cytokine, growth factor, receptor, inflammation, healing, fibrosis

Online: 28 May 2024 (09:19:20 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202308.0506.v1

Immune Checkpoint Inhibitors in Advanced Cutaneous Squamous Cell Carcinoma: Real-World Experience from a Canadian Comprehensive Cancer Centre

Erica Cristina Koch Hein, Maysa Vilbert, Ian Hirsch, Mauricio Fernando Ribeiro, Thiago Pimentel Muniz, Cynthia Fournier, Khaled Abdulalem, Erick Figueiredo Saldanha, Erika Martinez, Anna Spreafico, David Hartwick Hogg, Marcus Otho Butler, Samuel David Saibil

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: cemiplimab; pembrolizumab; immune checkpoint inhibitor; PD-1; cutaneous squamous cell carcinoma

Online: 7 August 2023 (10:37:53 CEST)

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Preprint ARTICLE | doi:10.20944/preprints201701.0023.v1

Urban Sprawl Detection Using Remotely Sensed Data: A Case of Chennai, Tamilnadu

Rajchandar Padmanaban, Pedro Cabral, Avit K. Bhowmik, Alexander Zamyatin, Oraib Almegdadi

Subject: Environmental And Earth Sciences, Remote Sensing Keywords: Random forest classification; urban sprawl; spatial metrics; Renyi’s entropy; sustainability; land change modelling; remote sensing; urban growth model; Chennai

Online: 5 January 2017 (09:20:29 CET)

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Preprint ARTICLE | doi:10.20944/preprints201611.0024.v3

Development of SWAT-Paddy for Simulating Lowland Paddy Fields

Ryota Tsuchiya, Tasuku Kato, Jaehak Jeong, Jeffrey G. Arnold

Subject: Environmental And Earth Sciences, Environmental Science Keywords: SWAT; water quality; paddy fields; irrigation; rice; watershed

Online: 13 September 2018 (08:42:30 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.0511.v1

Evaluation of the Impact of Advanced Glycation End-Products on Peripheral Neuropathy Outcomes in Type 2 Diabetes

Indumathi Singh, Tushar Issar, Ann Poynten, Kerry-lee Milner, Arun V Krishnan, Roshan Dhanapalaratnam

Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Advanced glycation end products; diabetic peripheral neuropathy

Online: 6 September 2024 (09:40:34 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1861.v1

A Comparison of Kawasaki Disease during the SARS-CoV-2 Pandemic with Multisystem Inflammatory Syndrome in Children

Tunç Tunçer, Fatih Varol

Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: Kawasaki disease; Multisystem inflammatory syndrome in children; SARS-CoV-2

Online: 26 August 2024 (15:25:39 CEST)

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Objectives: This study aimed to compare the similarities and differences between the Kawasaki disease (KD) during the SARS-CoV-2 pandemic and multisystem inflammatory syndrome in children (MIS-C). Methods: The medical records of patients diagnosed with KD and MIS-C at a single center between July 2020 and November 2021 were retrospectively reviewed. Results: The study included 39 MIS-C patients (84.6% male) with a median age of 138 months and 17 KD patients (58.8% male) with a median age of 36 months. Compared with the KD patients, MIS-C patients were older (p<0.001), had longer hospital stays (p=0.023), elevated neutrophil count (p<0.001), C-reactive protein (p<0.001), procalcitonin (p<0.001), interleukin-6 (p<0.014), ferritin (p<0.001), fibrinogen (p<0.001), troponin I (p=0.001), NT-proBNP (p<0.001), and, D-dimer levels (p<0.001). They had more hypotension (p=0.024), decreased left ventricular function (p=0.023), and a greater need for corticosteroids (p<0.001), enoxaparin (p=0.045), and therapeutic plasma exchange (p<0.001). Patients with KD displayed a higher frequency of rash (p<0.001), oral mucosal changes (p<0.001), conjunctival injection (p<0.001), extremity changes (p<0.001), and cervical lymphadenopathy (p<0.001). They had a longer duration of fever (p<0.001), elevated white blood cell count (p<0.001), platelet count (p<0.001), and alanine aminotransferase level (p<0.001). The two groups were similar in terms of hemoglobin levels, erythrocyte sedimentation rate, albumin levels, or the frequency of coronary dilation/aneurysm, myocarditis, pericarditis, invasive mechanical ventilatory support, and intravenous immunoglobulin treatment. Conclusions: Older patient age, a greater presence of gastrointestinal and cardiac findings associated with hypotension, increased NT-proBNP levels, decreased left ventricular function, the use of various treatment modalities, and longer hospital stays suggest MIS-C, whereas a longer duration of fever and classical clinical features of KD favor KD.

Preprint ARTICLE | doi:10.20944/preprints202408.1618.v1

Akkermansia muciniphila for the Prevention of Type 2 Diabetes and Obesity: A Meta-Analysis of Animal Studies

Ethan Liu, Xiangming Ji, Kequan Zhou

Subject: Biology And Life Sciences, Food Science And Technology Keywords: probiotic; Akkermansia; obesity; type 2 diabetes; animals; meta-analysis

Online: 22 August 2024 (08:25:55 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202407.0977.v2

Immunolocalization of Aquaporins 1, 2, and 9 in Anuran Testis of the Neotropical Pointedbelly Frog Leptodactylus podicipinus

Rafael Oliveira Alves Bordin, Classius de Oliveira, Raquel Fantin Domeniconi

Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: Anura; Aquaporin; Immunohistochemistry; Spermatogenesis

Online: 20 August 2024 (09:25:47 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.0940.v1

Impact of Vaccination on Intra-host Genetic Diversity of Patients Infected with SARS-CoV-2 Gamma Lineage

Beatriz de Carvalho Marques, Cecília Artico Banho, LIvia Sacchetto, Andreia Negri, Nikos Vasilakis, Maurício Lacerda Nogueira

Subject: Biology And Life Sciences, Virology Keywords: COVID-19, vaccination, Gamma lineage, negative selection, breakthrough infections

Online: 13 August 2024 (13:03:55 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.0622.v1

SAM2-Adapter: Evaluating & Adapting Segment Anything 2 in Downstream Tasks: Camouflage, Shadow, Medical Image Segmentation, and More

Tianrun Chen, Ankang Lu, Lanyun Zhu, Chaotao Ding, Chunan Yu, Deyi Ji, Zejian Li, Lingyun Sun, Ying Zang

Subject: Computer Science And Mathematics, Computer Vision And Graphics Keywords: Segment Anything; Adapter; Visual Prompting; Camouflaged; Shadow; Image Segmentation; Polyp Segmentation; Medical Image Segmentation

Online: 9 August 2024 (00:15:34 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202407.1568.v2

Sparsity Limit to Prune Large Language Models for on-Device AI Assistants: Llama-2 as an Example

Bo Liu, Yuru Xu

Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: large language models; sparse neural networks; pruning; on-device AI assistants

Online: 8 August 2024 (03:56:30 CEST)

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