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Preprint REVIEW | doi:10.20944/preprints202306.0039.v1

Cystic Clear Cell Renal Cell Carcinoma: A Morphological and Molecular Reappraisal

Giacomo Maria Pini, Roberta Lucianò, Maurizio Colecchia

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Renal cell carcinoma; Cystic renal neoplasm; differential diagnosis

Online: 1 June 2023 (07:03:38 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.2187.v1

Effects of diabetes mellitus related dysglycemia on the functions of blood-brain barrier and the risk of dementia

Mateusz Wątroba, Anna D. Grabowska, Dariusz Szukiewicz

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: diabetes mellitus; blood-brain barrier disruption; dysglycemia; hyperglycemia; insulin resistance; neurodegenerative disease; diabetic complications; dementia, diabetic encephalopathy

Online: 31 May 2023 (10:05:10 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.2189.v1

IL-23/IL-17 axis in the Chronic Hepatitis C and Nonalcoholic Steatohepatitis – New Insight Into Immunohepatotoxicity of Different Chronic Liver Diseases

Ankica Vujovic, Andjelka M Isakovic, Sonja Misirlic-Dencic, Jovan Juloski, Milan Mirkovic, Marina Djelic, Ivana Milošević

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: chronic hepatitis C; nonalcoholic steatohepatitis; IL-23/IL-17 axis; immunohepatotoxicity

Online: 31 May 2023 (07:46:51 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202305.1900.v1

Perforating Gout: Expanding the Differential for Transepidermal Elimination

Michal Bohdanowicz, Scott H Bradshaw

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Gout; Tophus; Perforating Dermatosis; Transepidermal Elimination; Pseudoepitheliomatous Hyperplasia; Granulomatous Dermatitis

Online: 26 May 2023 (09:36:26 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.1344.v1

Gray-Zone Lymphoma: A Still Open Issue

Stefano Pileri, Valentina Tabanelli, Chiarle Roberto, Angelica Calleri, Federica Melle, Giovanna Motta, Maria Rosaria Sapienza, Elena Sabattini, Pier Luigi Zinzani, Enrico Derenzini

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: mediastinal gray-zone lymphoma; classical Hodgkin lymphoma; primary mediastinal B-cell lymphoma; diffuse large B-cell lymphoma; NOS; EBV-positive diffuse large B-cell lymphoma; NOS; morphology; phenotype; gene expression profile; mutational landscape

Online: 18 May 2023 (12:25:07 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.0526.v1

Immuno-Contexture and Immune Checkpoint Molecule Expression in Microsatellite Stable/Mismatch Repair Proficient Colorectal Carcinoma

Mauro Giacomelli, Matilde Monti, Diego Cesare Pezzola, Silvia Lonardi, Mattia Bugatti, Francesco Missale, Rossella Cioncada, Laura Melocchi, Viviana Giustini, Vincenzo Villanacci, Carla Baronchelli, Stefania Manenti, Luisa Imberti, Emanuele Giurisato, William Vermi

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Colorectal cancer; mismatch repair; microsatellite instability; immune checkpoint; double negative T cells; tumor microenvironment; T-cell exhaustion; interferon-γ; PD-L1

Online: 8 May 2023 (10:53:18 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202304.0879.v1

The Utility of Mitochondria Detection Methods Applied as an Additional Tool for the Differentiation of Renal Cell Tumours

Gorana Nikolic, Maja Zivotic, Sanja Cirovic, Sanja Despotovic, Sanja Radojevic Skodric

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: renal cell tumours; renal cell carcinomas; immunohistochemistry; immunofluorescence; mito-chondria; electron microscopy

Online: 25 April 2023 (03:58:57 CEST)

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Preprint REVIEW | doi:10.20944/preprints202304.0694.v1

Medical Applications of Molecular Biotechnologies in the Context of the Hashimoto’s Thyroiditis

Maria Trovato, Andrea Valenti

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Hashimoto’s thyroiditis; molecular biotechnologies; clinical trials studies; hygiene hypothesis; parvoviruses

Online: 21 April 2023 (08:48:10 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202303.0225.v1

The Importance of Context in Inert Gas Asphyxiation Deaths: An Autopsy Case Report

Tyla Gelman, Andrew Sulaiman, Christine James, Diane Peterson

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Inert Gas Asphyxiation; Autopsy Case Report

Online: 13 March 2023 (09:44:40 CET)

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Preprint COMMUNICATION | doi:10.20944/preprints202303.0181.v1

Establishment of a Novel Anti-Human CCR6 Monoclonal Antibody C₆Mab-19 with the High Binding Affinity in Flow Cytometry

Tomohiro Tanaka, Kaishi Kitamura, Hiroyuki Suzuki, Mika K. Kaneko, Yukinari Kato

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: CCR6; monoclonal antibody; peptide immunization; flow cytometry; immunohistochemistry

Online: 9 March 2023 (13:45:12 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202303.0179.v1

Fatal Hemopericardium due to Rupture of the Ascending Aortic Artery in a Patient with Turner Syndrome: A Case Report with Autopsy Findings

Andrew Sulaiman, Tyla Gelman, Christine James, Diane Peterson

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Turner Syndrome; Autopsy Case Report

Online: 9 March 2023 (13:02:39 CET)

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Preprint REVIEW | doi:10.20944/preprints202303.0126.v1

Sarcoidosis, Mycobacterium paratuberculosis and Noncaseating Granulomas: Who Moved My Cheese

Coad Thomas Dow, Nancy W. Lin, Edward D. Chan

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: sarcoidosis; Mycobacterium avium ss. paratuberculosis; MAP; non-caseating granuloma; caseating granuloma; Blau syndrome; early onset sarcoidosis; Crohn’s disease; cell wall deficient (CWD); L-form; Mycobacterium tuberculosis; acid-fast bacilli; SLC11a1 (NRAMP1); NOD2 (CARD15)

Online: 7 March 2023 (03:46:55 CET)

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Preprint REVIEW | doi:10.20944/preprints202303.0091.v1

Unlocking the Therapeutic Potential of Irisin: Harnessing its Function in Degenerative Disorders and Tissue Regeneration

Yuwei Zhang, Lizhen Wang, Hongyan Kang, Chia-ying Lin, Yu-Bo Fan

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: FNDC5; Irisin; Degenerative disease; Regeneration; Tissue repair.

Online: 6 March 2023 (06:06:09 CET)

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Preprint REVIEW | doi:10.20944/preprints202303.0061.v1

A Landscape on Disorders Following Different COVID-19 Vaccination: A Systematic Review of Iranian Case Reports

Mona Sadat Larijani, Delaram Doroud, Mohammad Banifazl, Afsaneh Karami, Anahita Bavand, Fatemeh Ashrafian, Amitis Ramezani

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; Vaccination; Adverse event; Case report; Iran

Online: 3 March 2023 (08:30:15 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0178.v2

Performance of a 7-Type HPV mRNA Test in Triage of HPV DNA Primary Screen Positive Women Compared to Liquid-Based Cytology

Sveinung Wergeland Sørbye, Bente Marie Falang, Mona Antonsen

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: HPV-DNA; primary screening; HPV-mRNA; biomarker; triage; liquid-based cytology; colposcopy; CIN2+

Online: 28 February 2023 (01:50:35 CET)

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Preprint ARTICLE | doi:10.20944/preprints202302.0437.v1

Development of a Novel Anti-CD44 Variant 7/8 Monoclonal Antibody C44Mab-34 for Multiple Applications against Oral Carcinomas

Hiroyuki Suzuki, Kazuki Ozawa, Tomohiro Tanaka, Mika K. Kaneko, Yukinari Kato

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: CD44; CD44 variant 7/8; monoclonal antibody; flow cytometry; immunohistochemistry

Online: 27 February 2023 (04:13:02 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202302.0260.v1

COVID-19 and Vasa Vasorum: New Atherogenic Factor? A Case Report and Autopsy Findings

Julia Makarova, Sofia Malachova, Tatiana Novitskaya, Valeria Shapkina, Leonid Churilov

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; SARS-CoV-2; atherosclerosis

Online: 16 February 2023 (02:18:09 CET)

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Preprint ARTICLE | doi:10.20944/preprints202302.0207.v1

Mild Chronic Kidney Disease Associated with Low Bone Formation and Decrease in Phosphate Transporters and Signaling Pathways Gene Expression

Evdokia Bogdanova, Airat Sadykov, Galina Ivanova, Irina Zubina, Olga Beresneva, Natalia Semenova, Olga Galkina, Marina Parastaeva, Vladimir Sharoyko, Vladimir Dobronravov

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Chronic kidney disease; bone remodeling; static bone histomorphometry; inorganic phosphate transporters; intracellular signaling

Online: 13 February 2023 (08:46:13 CET)

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Preprint REVIEW | doi:10.20944/preprints202302.0177.v1

The Role of Inflammation in the Cellular and Molecular Mechanisms of Cardiopulmonary Complications of Sickle Cell Disease

Oluwabukola T Gbotosho, Jahnavi Gollamudi, Hyacinth I Hyacinth

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Sickle cell disease; cardiopulmonary complications; inflammation; acute chest syndrome; cardiac hypertrophy; cardiac fibrosis; diastolic dysfunction; pulmonary hypertension

Online: 10 February 2023 (03:13:42 CET)

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Preprint REVIEW | doi:10.20944/preprints202302.0148.v1

Activation of Mast Cells by Neuropeptides: The Role of Pro-inflammatory and Anti-Inflammatory Cytokines

Dorina Lauritano, Filiberto Mastrangelo, Cristian D’Ovidio, Gianpaolo Ronconi, Alessandro Caraffa, Carla E. Gallenga, Ilias Frydas, Spyros K. Kritas, Matteo Trimarchi, Francesco Carinci, Pio Conti

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Neuropeptide; Inflammation; Immunity; Mast cell: Pro-inflammatory cytokines; Anti-inflammatory cytokines

Online: 8 February 2023 (11:33:15 CET)

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Preprint REVIEW | doi:10.20944/preprints202302.0115.v1

Overview and New Insights into the Metabolic Syndrome: Risk Factors and Emerging Variables in the Development of Type 2 Diabetes and Cerebrocardiovascular Disease

Melvin R. Hayden

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Endothelial dysfunction; Exosomes; Hyperinsulinemia; Hyperglycemia; Hyperlipidemia; Hypertension; Insulin Resistance; Leptin Resistance; Metainflammation; miRNAs

Online: 7 February 2023 (03:07:09 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0583.v2

Cellular FXIII in Human Macrophage Derived Foam Cells

Laura Somodi, Emőke Horváth, Helga Bárdos, Barbara Baráth, Dávid Pethő, Éva Katona, József Balla, Nicola J Mutch, László Muszbek

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: factor XIII; foam cells; macrophages; vascular smooth muscle cells; oxidized LDL; enzyme-modified LDL; transglutaminase; atherosclerotic plaque; cross-linking

Online: 2 February 2023 (11:52:20 CET)

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Preprint ARTICLE | doi:10.20944/preprints202302.0033.v1

Long-term SMN- and Ncald-ASO Combinatorial Therapy in SMA Mice and NCALD-ASO Treatment in hiPSC-Derived Motor Neurons Show Protective Effects

Anixa Muiños-Bühl, Karen K Ling, Roman Rombo, Eleonora Zilio, Frank Rigo, C. Frank Bennett, Brunhilde Wirth

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Neuromuscular disorder; NCALD; SMA; SMN2; Antisense oligonucleotide; Genetic modifier; Therapy; hiPSCs;

Online: 2 February 2023 (07:54:05 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0583.v1

Cellular FXIII in Human Macrophage Derived Foam Cells

Laura Somodi, Emőke Horváth, Helga Bárdos, Barbara Baráth, Dávid Pethő, Éva Katona, József Balla, Nicola J Mutch, László Muszbek

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: factor XIII, foam cells, macrophages, vascular smooth muscle cells, oxidized LDL, enzyme-modified LDL, transglutaminase, atherosclerotic plaque, cross-linking

Online: 31 January 2023 (10:23:56 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0178.v1

Performance of a 7-type HPV mRNA Test in Triage of HPV DNA Primary Screen Positive Women Compared to Liquid-based Cytology

Sveinung Wergeland Sørbye, Bente Marie Falang, Mona Antonsen

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: HPV-DNA; primary screening; HPV-mRNA; biomarker; triage; liquid-based cytology; colposcopy; CIN2+

Online: 10 January 2023 (07:13:00 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0066.v2

Longitudinal Assessment of Plasma Syndecan-1 Predicts 60-Day Mortality in Patients with COVID-19

Quan Zhang, Zhan Ye, Antonia Bignotti, X. Long Zheng

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; endothelial dysfunction; glycocalyx degradation; sydencan-1; and mortality

Online: 9 January 2023 (03:21:59 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0131.v1

Prospective Validation of the ROL System in Substaging Pt1 High-Grade Bladder Cancer: Results from a Prospective Mono-Institutional Confirmatory Analysis in BCG Treated Patients

Marina Valeri, Roberto Contieri, Vittorio Fasulo, Miriam Cieri, Grazia Maria Elefante, Camilla De Carlo, Alessandra Bressan, Martina Iuzzolino, Cesare Saitta, Andrea Gobbo, Pier Paolo Avolio, Valerio Dacrema, Massimo Lazzeri, Gianluigi Taverna, Luigi Maria Terracciano, Rodolfo Hurle, Piergiuseppe Colombo

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: BCG; bladder cancer; non-muscle-invasive bladder cancer; prospective validation; pT1 high-grade bladder cancer; risk stratification; ROL; substaging; TURBT; urothelial carcinoma.

Online: 9 January 2023 (01:17:29 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0066.v1

Longitudinal Assessment of Plasma Syndecan-1 Predicts 60-Day Mortality in Patients with COVID-19

Quan Zhang, Zhan Ye, Antonia Bignotti, X. Long Zheng

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19, endothelial dysfunction, glycocalyx degradation, sydencan-1, and mortality.

Online: 4 January 2023 (04:37:40 CET)

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Preprint REVIEW | doi:10.20944/preprints202301.0065.v1

Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome – An Extempore Game of Bursting Firecrackers with Defense Arsenals

Vignesh Ramachandran, Pachamuthu Balakrishnan, Hong Yien Tan, Yean Kong Yong, Vijayakumar Velu, Marie Larsson, Esaki M Shankar

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: ART; Biomarkers; Inflammation; IRIS; Tuberculosis

Online: 4 January 2023 (04:18:55 CET)

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Preprint ARTICLE | doi:10.20944/preprints202301.0061.v1

Natural Language Processing Accurately Categorizes Indications, Findings, and Pathology Reports from Multicenter Colonoscopy

Shashank reddy Vadyala

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Neural Network; Machine Learning; Natural Language Processing (NLP); Text Mining; Sentence Classification; Colorectal Cancer; Clinical Information.

Online: 4 January 2023 (03:48:26 CET)

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Preprint ARTICLE | doi:10.20944/preprints202212.0457.v1

Residual Humidity in Paraffin Embedded Tissue Reduces Nucleic Acid Stability

Peter M. Abuja, Daniela Pabst, Benjamin Bourgeois, Martina Loibner, Christine Ulz, Iris Kufferath, Ulrike Fackelmann, Conny Stumptner, Rainer Kraemer, Tobias Madl, Kurt Zatloukal

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: fixed tissue; nucleic acid quality; next-generation sequencing,

Online: 23 December 2022 (09:04:08 CET)

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Preprint REVIEW | doi:10.20944/preprints202212.0422.v1

An Old Acquaintance. Could Adenovirus be our Next Pandemic Threat?

Gustavo Enrique Saint-Pierre, Daniel Conei, Luis Lizama, Daniela Vargas, Luis Fidel Avendaño, Sandra Ampuero

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Infections; Human Adenovirus; Social Determinants of Health; Adenovirus Vaccine; Genotype; Molecular Diagnostic Testing

Online: 22 December 2022 (07:05:34 CET)

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Preprint ARTICLE | doi:10.20944/preprints202212.0401.v1

Involvement of the Small ncRNAome in Fresh Peripheral Blood Mononuclear Cells of Human T-cell Leukemia Virus Type I- Associated Myelopathy/Tropical Spastic Paraparesis Patients and Viral Carriers

Daniela R. V. Souza, Rodrigo Pessôa, Youko Nukui, Juliana Pereira, Rosa Nascimento Marcusso, Augusto César Penalva de Oliveira, Jorge Casseb, Alberto José da Silva Duarte, Patricia Bianca Clissa, Sabri Saeed Sanabani

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: small RNA; HTLV-1; HAM/ TSP; massive parallel sequencing

Online: 21 December 2022 (11:46:09 CET)

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Preprint ARTICLE | doi:10.20944/preprints202212.0392.v1

Development of a Novel Anti-CD44 Variant 4 Monoclonal Antibody, C₄₄Mab-108

Hiroyuki Suzuki, Tomohiro Tanaka, Teizo Asano, Nohara Goto, Mika K. Kaneko, Yukinari Kato

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: CD44; CD44 variant 4; monoclonal antibody; flow cytometry; immunohistochemistry

Online: 21 December 2022 (07:40:21 CET)

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Preprint ARTICLE | doi:10.20944/preprints202212.0359.v1

Spatial Distribution and Clustering of Drug-Resistant Mycobacterium Tuberculosis Infections in Rural Eastern Cape Province of South Africa

Lindiwe M. Faye, Mojisola C. Hosu, Sandeep Vasaikar, Anzaan Dippenaar, Selien Oostvogels, Teke Apalata

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: tuberculosis; spatial analysis; mutations; spoligotypes; heteroresistance; cluster

Online: 20 December 2022 (08:10:25 CET)

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Preprint ARTICLE | doi:10.20944/preprints202212.0275.v1

Bioinformatics and Connectivity Map Analysis Suggest Viral Infection as a Critical Causative Factor of Hashimoto’s Thyroiditis

Dong-Woo Lim, Min-Seo Choi, Seok-Mo Kim

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Hashimoto’s thyroiditis; bioinformatics; viral infection; mRNA splicing; GSEA; autoimmune disease; CMap

Online: 15 December 2022 (07:44:33 CET)

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Hashimoto’s thyroiditis (HT) is a common autoimmune disease, with its prevalence rapidly increasing. Both genetic and environmental risk factors contribute to the development of HT. Recently, viral infection has been suggested to act as a trigger of HT by eliciting the host immune response and subsequent autoreactivity. We analyzed features of HT through bioinformatics analysis so as to identify markers of HT development. We accessed public microarray data of HT patients from the Gene Expression Omnibus (GEO) and obtained differentially expressed genes (DEGs) under HT. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed for functional clustering of our protein-protein interaction (PPI) network. Utilizing ranked gene lists, we performed Gene Set Enrichment Analysis (GSEA) using the clusterprofiler R package. By comparing the expression signatures of the huge perturbation database with the queried rank-ordered gene list, connectivity map (CMap) analysis was performed to screen potential therapeutic targets and agents. The gene expression profile of the HT group was in line with general characteristics of HT. Biological processes related to the immune response and viral infection pathways were obtained for the upregulated DEGs. GSEA results revealed activation of autoimmune disease-related pathways and several viral infection pathways. Autoimmune disease and viral infection pathways were highly interconnected by common genes, while the HLA genes which are shared by both were significantly upregulated. CMap analysis suggested that perturbagens, including SRRM1, NLK, and CCDC92, have the potential to reverse the HT expression profile. Several lines of evidence suggested that viral infection and the host immune response are activated during HT. Viral infection is suspected to act as a key trigger of HT by causing autoimmunity. SRRM1, an alternative splicing factor, which responds to viral activity, might serve as potential marker of HT.

Preprint ARTICLE | doi:10.20944/preprints202212.0073.v1

Rapid Evaluation of the Xpert ® Xpress CoV-2 Plus and Xpert® Xpress CoV-2/Flu/RSV Plus Tests

Lara Dominique Noble, Lesley Erica Scott, Riffat Munir, Mignon Du Plessis, Kim Steegen, Lucia Hans, Puleng Marokane, Pedro Da Silva, Wendy Susan Stevens

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-COV-2; respiratory tests; Xpert® Xpress COV-2 plus; Xpert(2) Xpress COV-2/Flu/RSV plus; diagnostic evaluation; novel target

Online: 5 December 2022 (10:17:58 CET)

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The Xpert® Xpress SARS-CoV-2 and Xpert® Xpress SARS-CoV-2/Flu/RSV tests were rapidly developed and widely used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In response to emerging genetic variability, a new SARS-CoV-2 target (RNA-dependent RNA-polymerase) has been added to both tests: Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus test. A rapid evaluation of both tests was performed in South Africa, using residual respiratory specimens. Residual respiratory specimens (n=125) were used to evaluate the Xpert® Xpress CoV-2 plus test and included 50 genotyped specimens. The Xpert® Xpress CoV-2/Flu/RSV plus test was assessed using 45 genotyped SARS-CoV-2 specimens, ten influenza A, ten Influenza B and twenty respiratory syncytial virus specimens. Results were com-pared to in-country standard of care tests. Genotyped specimens tested the performance of the test under pressure from circulating SARS-CoV-2 variants of concern. Reference material was included to assess the test limits and linearity. The Xpert® Xpress CoV-2 plus test performance compared to reference results across residual respiratory specimens was good (positive per-centage agreement (PPA)=95.2%, negative percentage agreement (NPA)=95.0%) The Xpert® Xpress CoV-2/Flu/RSV plus test showed good performance across all residual respiratory specimens (PPA=100%, NPA=98.3%). All genotyped variants of concern were detected by both tests. The Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus tests can be used to diagnose SARS-CoV-2, and to diagnose and differentiate SARS-CoV-2, influenza A, influenza B and respiratory syncytial virus respectively. The NPA was lower than the recommended 99%, but was influenced by the low number of negative specimens tested. The variants of concern assessed did not affect test performance. It is recommended that sites perform their own assessments compared to in-country standard of care tests.

Preprint REVIEW | doi:10.20944/preprints202212.0066.v1

Thrombo-inflammation in COVID-19 and Sickle Cell Disease: Two Faces of the Same Coin

Kate Chander Chiang, Ajay Gupta, Prithu Sundd, Lakshmanan Krishnamurti

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Sickle Cell Disease; COVID-19; SARS-CoV-2; Vaso-occlusive Crisis; Pain; Thromboxane; Prostaglandin D2; Thrombo-inflammation; Acute Chest Syndrome; Ramatroban

Online: 5 December 2022 (08:00:45 CET)

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Preprint ARTICLE | doi:10.20944/preprints202211.0560.v1

Eosinophilic Inflammation and Its Association with Small Airway Dysfunction in COPD Patients by Biomass

Oliver Pérez-Bautista, Rogelio Pérez-Padilla, Alejandra Ramírez-Venegas, Yadira Velasco-Torres, Martha Montaño, Carlos Ramos

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: airways obstruction; biomass smoke; COPD; cytokines; eosinophils; impulse oscillome-try; tobacco smoking

Online: 30 November 2022 (03:40:46 CET)

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Preprint ARTICLE | doi:10.20944/preprints202211.0529.v1

Surveillance of Daughter Micronodule Formation is A Key Factor for Vaccine Evaluation Using Experimental Infection Models of Tuberculosis in Macaques

Isabel Nogueira, Martí Català, Andrew D White, Sally A Sharpe, Jordi Bechini, Clara Prats, Cristina Vilaplana, Pere-Joan Cardona

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: tuberculosis; BCG vaccine; aerosol vaccination; non-human primate; macaque; bubble model; computed tomography scanner

Online: 29 November 2022 (03:29:53 CET)

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Preprint ARTICLE | doi:10.20944/preprints202211.0498.v1

SARS-CoV-2 Virus-Like Particles (VLPs) specifically detect humoral immune reactions in an ELISA based platform

Stefan Hirschberg, Hannes Bauer, Julian Kamhieh-Milz, Frauke Ringel, Christoph Harms, Omar Kamal Eddin, Axel Pruß, Katja Hanack, Kai Schulze-Forster

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Virus-Like Particle (VLP); SARS-CoV-2; in vitro diagnostic device (IVD); Enzyme-linked Immunosorbent Assay (ELISA); Immune reaction; Antibodies

Online: 28 November 2022 (07:06:50 CET)

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Preprint ARTICLE | doi:10.20944/preprints202211.0086.v1

Evaluation of Serological Tests to Determine Postvaccinal Immunity to SARS-Cov-2 by Mrna Vaccines

Graciela Iglesias García, Ángel Díaz Rodíguez, Beatriz Díaz Rodríguez, Carmela Cuello Estrada, Tania Ferreiro García, Noelia Crespo García, Jesús Seco-Calvo

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: automated immunoassays; COVID-19; lateral flow immunoassay; performance; SARS-CoV-2

Online: 4 November 2022 (01:59:01 CET)

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Preprint ARTICLE | doi:10.20944/preprints202210.0421.v1

Circulating Levels of Ferritin, RDW, PTLs as Predictive Biomarkers of Postoperative Atrial Fibrillation Risk after Cardiac Surgery in Extracorporeal Circulation

Claudia Altieri, Calogera Pisano, Vincenzo Labriola, Maria Sabrina Ferrante, Anna Maria Porreca, Paolo Nardi, Carlo Bassano, Dario Buioni, Ernesto Greco, Giovanni Ruvolo, Carmela Rita Balistreri

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Postoperative atrial fibrillation; cardiac surgery; conventional extracorporeal circulation; circulating ferritin levels; POAF onset biomarker

Online: 27 October 2022 (05:53:09 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202210.0306.v1

Altered Cortical Palmitoylation Induces Widespread Molecular Disturbances in Parkinson´s Disease

Juan F. Cervilla-Martinez, Juan J. Rodriguez-Gotor, Krzysztof J. Wypijewski, Ángela Fontán-Lozano, Tao Wang, Enrique Santamaría, William Fuller, Rebeca Mejías

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Parkinson´s disease; proteomics; cerebral cortex; palmitoylation; interactome.; fibrinogen; cytoskeleton

Online: 20 October 2022 (11:14:12 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202210.0195.v2

Antioxidants and Long Covid

Patrick Chambers

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Warburg effect, oxidative stress, magnesuria, inflammasome, butyrate

Online: 14 October 2022 (12:56:34 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202210.0195.v1

Antioxidants and Long Covid

Patrick Chambers

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Warburg effect, oxidative stress, magnesuria, inflammasome, butyrate

Online: 13 October 2022 (13:38:59 CEST)

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Preprint REVIEW | doi:10.20944/preprints202210.0083.v1

Epigenetic Connections of the TRPA1 Ion Channel in Pain Transmission and Neurogenic Inflammation – A Therapeutic Perspective in Migraine?

Michal Fila, Janusz Blasiak, Elzbieta Pawlowska

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: epigenetics; TRP channels; TRPA1; pain transmission; neuropathic pain; neurogenic inflammation; migraine; DNA methylation; histone modification; micro RNA

Online: 7 October 2022 (15:21:34 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202209.0439.v1

SARS-CoV-2 Detection in Fecal Samples in Sym-asymptotic Patients with Typical Findings of COVID-19 on Ag-RDT and SARS-CoV-2 RT-PCR Tests

Richard Odongo Magwanga, Benson Onyango, Alfred Ochieng, Shehu Shagari Awandu, Pamela Were, Joy Nyangasi Kirungu, Marceline Adhiambo Oloo, Erick Muok, Stephen Munga, Fredrick Ogutu, Angeline Orwa, Fredrick Okumu, Clayton Onyango, Dorothy Awuor, Francis Orata, Justine Ochieng’-Midega, Bonface Oure, Regina Nyunja, Fredrick Ade, Sharley Indechi, Erick Okuto, Benson Estambale

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID19; SARS-CoV-2 virus; Oro-nasopharyngeal; fecal; vaccination; asym-symptomatic; rapid diagnostic test

Online: 28 September 2022 (11:51:21 CEST)

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Coronavirus is a disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged as a global pandemic in 2019 from Wuhan, China. Since its emergence, it has caused immense suffering to human life, 6.27 million lives have been lost, movement curtailed and social dynamics disrupted. The golden standard for getting samples for SARS-CoV-2 detection is through oral- nasopharyngeal swab, this method of sample collection is invasive and uncomfortable, thus stigmatized the general population, and thereby impeded the progress of controlling the spread through mass testing. Being a contact disease, mechanisms to encourage mass testing is key to reduce the spread. This study thus developed a complimentary sample type to test for SARS-CoV-2, the use of human feces. Fecal samples were collected from 100 asym-symptomatic individuals suspected to be infected with COVID-19, virus RNA was then extracted and profiled through Real Time Polymerase Chain Reaction (RT-qPCR). The antigen rapid diagnostic test revealed high positivity rate of 44%, but the real time polymerase chain reaction results on nasopharyngeal and fecal samples revealed a significant variation, high number of the patients tested positive with stool samples compared to the nasopharyngeal swabs, with 43 and 37%, respectively. SARS-CoV-2 virus was detected in both symptomatic and asymptomatic individuals; however, the symptomatic registered a higher positivity of 25% compared to 20% among the asymptomatic patients. Vaccination only lowered the risk of infection, fully and partially vaccinated lowered the infection level to 10% compared to 20% among the unvaccinated. Finally, gender parity in relation to COVID19 was evaluated, more females (56%) compared to males were recruited in this study, out of which (20; 43.4%) were positive, and 26 (56.6%) were negative based on fecal RT-qPCR outcomes. Based on the outcome of this study, rapid diagnostic test (Ag-RDT) however cheap and or fast does not provide accurate information, moreover, the virus does not stay longer within the Oro-nasopharyngeal region, thus the invalid or negative results, thus use of feces should be adopted as a confirmatory test to ascertain the COVID19 status of an individual.

Preprint ARTICLE | doi:10.20944/preprints202209.0253.v1

Type I interferon receptor subunit 1 deletion attenuates experimental abdominal aortic aneurysm formation

Takahiro Shoji, Jia Guo, Yingbin Ge, Yankui Li, Gang Li, Toru Ikezoe, Wei Wang, Xiaoya Zheng, Sihai Zhao, Naoki Fujimura, Jianhua Huang, Baohui Xu, Ronald L. Dalman

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Abdominal aortic aneurysm; Type I interferon receptor, Leukocytes; Angiogenesis

Online: 19 September 2022 (02:08:07 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202209.0161.v1

Daratumumab Interferes with Histocompatibility Crossmatch Impacting Immunological Assessment in Solid Organ Transplantation

Chak-Sum Ho, Kyle R. Putnam, Christine R. Peiter, Walter Herczyk, John A. Gerlach, Yee Lu, Erica L. Campagnaro, Kenneth J. Woodside, Matthew F. Cusick

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Antibody-mediated rejection; Crossmatch; Daratumumab; End-stage renal disease; Flow cytometry; HLA; Multiple myeloma; Transplantation

Online: 13 September 2022 (05:48:27 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202209.0137.v1

Machine Learning Classification of Specific Serologic Cytokines May Improve Detection of Recent, Fall Induced, Sub-Concussional Brain Changes in Geriatric Nondemented Subjects

Eduard Drima, Camelia Vrabie

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Chronic geriatric inflammation; machine learning C4.5 classification; brain ventricular volumes; recent fall; subconcussive brain trauma

Online: 9 September 2022 (13:05:28 CEST)

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Preprint REVIEW | doi:10.20944/preprints202209.0123.v1

Falls Incidence and Associated Risk Factors among People with Chronic Obstructive Pulmonary Disease (COPD)

Mehrdad Davoudi, Seyyed Mohammadreza Shokouhyan, Mohsen Abedi, Mehdi Rezaei, Mohamad Parnianpour, Kinda Khalaf, Masood Mazaheri

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: chronic obstructive pulmonary disease; COPD; fall risk factor; gait; balance; cognition; daily activity; muscle dysfunction

Online: 8 September 2022 (10:35:01 CEST)

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Chronic obstructive pulmonary disease (COPD) is increasingly being recognized as a systemic disease rather than a mere disorder of the lungs. Central (respiratory) and peripheral (limb) muscle weakness are among the main pronounced systemic effects of COPD. While the disease primarily affects the lower limb muscles and contributes to gait impairment, COPD is also associated with an increasing risk of falls in patients (COPDp). Previous studies have reported higher rates of falls among COPDp (1.17 to 1.20 falls/person-year), amounting to four times higher than an age-matched healthy group. Potential fall risk factors include muscle weakness, impaired daily activities, cognitive dysfunction, and gait and balance impairment. Although COPDp often manifest many of these risk factors, there remains a gap in literature regarding falls during walking in this population. This study aimed to 1. analyze the literature to identify the risk factors of falling in COPDp, and 2. investigate the underlying mechanisms by which these risk factors can lead to increased prevalence of falling. The results suggest that in addition to the known risk factors of falling, low back pain and mental fatigue should also be considered as relevant risk factors in the treatment process of these patients. Moreover, respiratory problems, which are common in this population, have demonstrated pronounced effects on energy expenditure, gait, and other types of activities of daily living (ADLs), leading to reduced intensity, disrupted coordination of the trunk-pelvic structure with the lower limbs during gait, and altered motor control performance due to activation of muscles in an inefficient synergic manner. These problems potentially lead to the increased vulnerability of these patients to external disturbances and higher incidence risk of falls and injuries. Cognitive problems, which are typically due to reduced oxygen received by the brain, as well as general inflammation caused by COPD, also play a significant role in gait disruption and balance. Future research is warranted to determine the prevalence of falls in COPDp by examining the response of these patients to Medio-Lateral (ML) and Anterior-Posterior (AP) disturbances during gait in association with traditional and recommended fall risk factors.

Preprint REVIEW | doi:10.20944/preprints202209.0115.v1

Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases

Joanne K Tobacman, Sumit Bhattacharyya

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: : N-acetylgalactosamine-4-sulfatase; Arylsulfatase B; chondroitin 4-sulfate; dermatan sulfate; sulfated glycosaminoglycans; mucopolysaccharidosis; cystic fibrosis; malignancy; proteoglycans; Warburg effect

Online: 8 September 2022 (03:07:30 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202209.0079.v1

Hepatitis C Core Protein Induces a Genotype-specific Susceptibility of Hepatocytes to TNF-induced Death in vitro and in vivo

Savvina Moustafa, Katerina Kassela, Maria Bampali, Nikolas Dovrolis, Athanassios Kakkanas, Apostolos Beloukas, Penelope Mavromara, Ioannis Karakasiliotis

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Hepatitis C virus; core protein; TNFα

Online: 6 September 2022 (03:38:14 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202209.0051.v1

A Case Report: Acute Myocardial Infarction, Coronal Arteritis and Myocarditis after BNT162b2 mRNA Vaccination against Covid-19

Michael Mörz

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: mRNA Vaccine; autopsy

Online: 5 September 2022 (08:14:56 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202206.0308.v2

A Case Report: Multifocal Necrotizing Encephalitis and Myocarditis after BNT162b2 mRNA Vaccination against Covid-19

Michael Mörz

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: mRNA Vaccine; autopsy

Online: 25 August 2022 (03:54:58 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202208.0378.v1

Frequency and Antibiotic Susceptibility Patterns of Streptococcus Agalactiae Strains Isolated from Women in Yaounde, Cameroon

Cécile Ingrid Djuikoue, Paule Dana Djouela Djoulako, Rodrigue Kamga Wouambo, Rosine Yemetio Foutsa, Dorine Ekeu, Teke Apalata

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Antibiotic resistance; Colonization; Prevalence; GBS; Resistance phenotype

Online: 22 August 2022 (08:04:16 CEST)

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Group B Streptococcus (GBS), a commensal in the body, causes a wide range of infectious diseases. The colonisation levels of GBS and its resistance profile to antibiotics provide important information useful for orienting prevention strategies. There is little data available on the subject with determination of resistance phenotypes in Cameroon. We therefore aimed to determine the prevalence of colonization, antibiotic resistance, including patterns of inducible resistance to clindamycin of GBS in Yaounde. To achieve this goal, a prospective cross-sectional study with an analytical component was carried out from the 28th June to the 29th August 2020 at the BIOSANTE laboratory and the Yaounde Gynaeco-Obstetrics and Paediatrics hospital. Vaginal swabs and urine were collected on 163 women. This samples were analysed using 5% defibrinated sheep blood agar and chocolate plus polyvitex agar. The isolates were identified using the morphology of the colony, Gram staining, haemolysis, catalase test and latex grouping test. Antibiotic susceptibility testing was done by disk diffusion method following the recommendations of the ACFSM 2019. The double disk diffusion method was used to identify isolates with clindamycin inducible resistance. Our data was analysed by the software SPSS version 2.1. The results obtained showed that the global prevalence of colonization by GBS was 37% (57/163), 40.35% in non-pregnant women and 59.65% in pregnant women. Pregnancy (P-value = 0.019) and gestational age (P-value = 0.025) constituted the risk factors of maternal colonization by GBS. In addition, the strains of GBS were resistant to all antibiotics tested. A D test showcased that 64.7% of GBS were resistant in a constitutive manner to clindamycin. We also note the presence of M phenotypes. As a whole, our results demonstrate that the rate of GBS colonization in this study was similar or higher than those in the previous report in Cameroon. All this indicates that attention should be paid to this bacterium in the monitoring of antimicrobial resistance and in the care of pregnant women and newborns.

Preprint ARTICLE | doi:10.20944/preprints202208.0244.v1

Post-injury Buprenorphine Administration Is Associated With Long-Term Region-Specific Glial Alterations in Rats

Jane Ryu, Pantea Jeizan, Saira Ahmed, Sareena Ehsan, Jefin Jose, Sean Regan, Karen Gorse, Corrina Kelliher, Audrey Lafrenaye

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Traumatic brain injury; buprenorphine; Bup-SR-Lab; microglia; astrocyte; myelin, membrane disruption; somatosensory sensitivity

Online: 12 August 2022 (13:52:14 CEST)

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Traumatic brain injury (TBI) is a major leading cause of death and disability. While previous studies regarding focal pathologies following TBI have been done, there is a lack of information concerning the role of analgesics and their influences on injury pathology. Buprenorphine (Bup), an opioid analgesic, is a commonly used analgesic in experimental TBI models. Our previous studies investigated the acute effects of Buprenorphine-sustained release-Lab (Bup-SR-Lab) on diffuse neuronal/glial pathology, neuroinflammation, cell damage, and systemic physiology. The current study investigated the longer-term chronic outcomes of Bup-SR-Lab treatment at 4 weeks following TBI utilizing a central fluid percussion injury (cFPI) model in adult male rats. Histological assessments of physiological changes, neuronal damage, cortical and thalamic cytokine expression, microglial and astrocyte morphological changes, and myelin alterations were done, as we had done in our acute study. In the current study the Whisker Nuisance Task (WNT) was also performed pre- and 4w post-injury to assess changes in somatosensory sensitivity following saline or Bup-SR-Lab treatment. Bup-SR-Lab treatment had no impact on overall physiology or neuronal damage at 4w post-injury regardless of region or injury, nor did it have any significant effects on somatosensory sensitivity. However, greater IL-4 cytokine expression with Bup-SR-Lab treatment was observed compared to saline treated animals. Microglia and astrocytes also demonstrated region-specific morphological alterations associated with Bup-SR-Lab treatment, in which cortical microglia and thalamic astrocytes were particularly vulnerable to Bup-mediated changes. There were discernable injury-specific and region-specific differences regarding myelin integrity and changes in specific myelin basic protein (MBP) isoform expression following Bup-SR-Lab treatment. This study indicates that use of Bup-SR-Lab could impact TBI-induced glial alterations in a region-specific manor 4w following diffuse brain injury.

Preprint REVIEW | doi:10.20944/preprints202207.0400.v1

Sergei Jargin

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: asbestos; chrysotile; mesothelioma; lung cancer

Online: 26 July 2022 (09:43:02 CEST)

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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 REVIEW | doi:10.20944/preprints202204.0078.v2

Big Data in Laboratory Medicine – FAIR Quality for AI?

Tobias Ueli Blatter, Harald Witte, Christos Theodoros Nakas, Alexander Benedikt Leichtle

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: digitalization; clinical chemistry; artificial intelligence; interoperability; FAIRification

Online: 15 July 2022 (05:00:44 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202207.0149.v1

Molecular and Source-Specific Profiling of Hospital Staphylococcus Aureus Reveal Dominance of Skin Infection and Age-Specific Selections in Pediatrics and Geriatrics

Kamaleldin B. Said, Naif Saad Alghasab, Mohed Saleem Elias

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: clinical S.aureus; skin carriage; geriatric-MRSA pneumonia; endogenous-S.aureus

Online: 11 July 2022 (04:33:22 CEST)

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The changing epidemiology of Staphylococcus aureus has created several gaps in its population structure and emergence of strains. Two global shifts in the aftermath of the past methicil-lin-resistant S. aureus (MRSA) pandemic are: a rise in healthcare-associated infections and evolu-tion of cutaneous and soft tissue infections with high morbidities and mortalities. Furthermore, bitter lessons from COVID-19 showed S. aureus necrotizing-pneumonia and skin conditions ag-gravating Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Monkeypox manifestations. Limited data and paucity of high-quality evidence exist for many key clinical questions. Using clinical microbiology, molecular characterization, hospital data on age and in-fection sites, and antibiograms, we have investigated S. aureus infection patterns. We showed that age-specific distribution in both intensive care unit (ICU) and non-ICU revealed highest infection rates (94.7%) in senior-patients >50 years; most were MRSA (81.99%). However, specific distribu-tions of geriatric MRSA and MSSA rates were 46.5% and 4.6% in ICU and 35.48% and 8.065% in non-ICU, respectively. Intriguingly, age groups 0-20 years showed uniquely similar MRSA pat-terns in ICU and non-ICU patients (13.9%, 9.7%, respectively) and MSSA in ICU (11.6%). In age groups 20-50 years, MRSA were 2-fold in non-ICU (35%) than ICU (18.6%). Interestingly, highly significant association was found between infection-site and age-groups (P-value .000). Skin in-fections remained higher in all ages; pediatrics 32.14%, adults 56%, and seniors 25% while res-piratory infections were lower in pediatrics (14.3%) and adult 17%), and highest in seniors (38%). Blood and “other” sites in pediatrics recorded (28.6%; 25%, respectively), slightly lower in adults (18.6%; 8.6%) and seniors (14%); 22.8%), respectively. Further, significant association existed between infection-site and MRSA (Chi-Square Test, P-value .002). The common cutaneous infec-tions across all age-groups and the significant association of MRSA to geriatric-respiratory infec-tions have a high potential for skin-carriage as reservoir for endogenous infection. The similar frequencies of both lineages in youth in all settings imply MSSA-carriage as potential evolutionary origins for MRSA. These findings have important clinical implications for strategic planning in patient management and S. aureus control particularly in age-specific infections and vigilance for potential viral coinfections.

Preprint ARTICLE | doi:10.20944/preprints202206.0359.v1

Biomolecular Fluorescence Complementation Profiling and Artificial Intelligence Structure Prediction of the Kaposi’s Sarcoma-associated Herpesvirus ORF18 and ORF30 Interaction

Yoshiko Maeda, Tadashi Watanabe, Taisuke Izumi, Kazushi Kuriyama, Shinji Ohno, Masahiro Fujimuro

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Kaposi’s sarcoma-associated virus (KSHV); Viral pre-initiation complex (vPIC); Bimolecular fluorescence complementation (BiFC); Artificial intelligence (AI) structure prediction; AlphaFold2

Online: 27 June 2022 (10:15:34 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202206.0308.v1

A Case Report: Multifocal Necrotizing Encephalitis and Myocarditis after BNT162b2 mRNA Vaccination against Covid-19

Michael Mörz

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: mRNA Vaccine; autopsy

Online: 22 June 2022 (07:53:57 CEST)

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Preprint REVIEW | doi:10.20944/preprints202206.0302.v1

Proteomic Discovery and Validation of Novel Fluid Biomarkers for Improved Patient Selection and Prediction of Clinical Outcomes in Alzheimer’s Disease Patient Cohorts

Shivangi Awasthi, Daniel S. Spellman, Nathan Galen Hatcher

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Neuroproteomics; Alzheimer’s disease biomarker; neurodegeneration

Online: 22 June 2022 (03:44:49 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202206.0266.v1

Angiogenic Burst After Parp Inhibitor Maintenance Therapy in Relapsed Ovarian Cancer: A Case Report

Lifeng Lin, Rongkui Luo, Wen Gao, Ping Zhang, Yingyong Hou, Rongyu Zang, Tingyan Shi

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: PARP inhibitor; angiogenesis; immune suppression; recurrent ovarian cancer

Online: 20 June 2022 (10:02:09 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202206.0063.v1

Extracellular Alterations in Ph and K+ Modify the Murine Brain Endothelial Cell Total and Phospho-Proteome

Jared Wahl, Anjali Vivek, Seph M. Palomino, Moyad Almuslim, Karissa E. Cottier, Paul R Langlais, John M. Streicher, Todd W. Vanderah, Erika Liktor-Busa, Tally M. Largent-Milnes

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Blood Brain Barrier; pH; Proteome; Phospho-Proteome; Endothelial

Online: 6 June 2022 (05:51:59 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202206.0010.v1

The SARS-CoV-2 S1 Spike Protein Promotes MAPK and NF-kB Activation and Inflammatory Cytokine Production In Human Lung and Intestinal Epithelial Cells

Christopher B Forsyth, Lijuan Zhang, Abhinav Bhushan, Barbara A. Swanson, João I. Mamede, Maliha Shaikh, Li Zhang, Ali Keshavarzian

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; ARDS; Cytokine Storm; Spike S1 protein; SARS-CoV-2, Long COVID; ACE2; A549 cells; Caco-2 cells

Online: 1 June 2022 (09:49:27 CEST)

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Preprint COMMUNICATION | doi:10.20944/preprints202205.0330.v1

Variant Allele of ALDH2, rs671 Associates with Attenuated Post-Vaccination Response in Anti-SARS-CoV-2 Spike Protein IgG: A Prospective Study in the Japanese General Population

Akiko Matsumoto, Megumi Hara, Mohammad Said Ashenagar, Mikiko Tokiya, Takeshi Sawada, Chiharu Iwasaka, Takuma Furukawa, Kyoko Kitagawa, Yasunobu Miyake, Yoshio Hirota

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: ALDH2; rs671; COVID-19; vaccine; immunogenicity

Online: 24 May 2022 (10:08:35 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202205.0216.v2

Comprehensive Biotechnical System for Screening Risk-Based Diagnosis of COVID-19 and Post-COVID Syndrome

Vladimir Savostyanov, Alexander Kobelev, Ivan Kudashov

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Bioimpedance; COVID-19; E-health; Health Care Personnel; Pathophysiology; Post-COVID syndrome; Rheography

Online: 23 May 2022 (05:26:58 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202205.0216.v1

Comprehensive Biotechnical System for Screening Risk-Based Diagnosis of COVID-19 and Post-COVID Syndrome

Vladimir Savostyanov, Alexander Kobelev, Ivan Kudashov

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Bioimpedance; COVID-19; E-health; Health Care Personnel; Pathophysiology; Post-COVID syndrome; Rheography

Online: 17 May 2022 (03:13:32 CEST)

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Preprint REVIEW | doi:10.20944/preprints202205.0189.v1

Machine Learning of Raman Spectroscopy Data for Classifying Cancers: a Review of the Recent Literature

Nathan Blake, Riana Gaifulina, Lewis D. Griffin, Ian M. Bell, Geraint M. H. Thomas

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Raman Spectroscopy; Medical application; Disease screening and diagnosis; Machine learning analyses

Online: 13 May 2022 (10:17:00 CEST)

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Preprint REVIEW | doi:10.20944/preprints202205.0158.v1

Histone Deacetylases as Epigenetic Targets for Treating Parkinson’s Disease

Yan Li, Zhicheng Gu, Shu-xian Lin, Lei Chen, Valentina Dzreyan, Moez Eid, Svetlana Demyanenko, Bin He

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Parkinson’s disease; Epigenetic targets; Histone deacetylases; Inhibitors; PROTACs

Online: 12 May 2022 (05:41:21 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202205.0127.v1

Association Between Systemic Arterial Hypertension with Laboratory Markers, Body Composition, Obstructive Sleep Apnea and Heart Rate Variability in Obese Adults

Clarcson Santos, Laura Lagares, Sarah Santos, Felipe Santos, Mariana Silva, Rodrigo Macedo, Luiz Almeida, Eric Bomfim

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: hypertension; obesity; body composition; intra-abdominal fat; sleep apnea; obstructive

Online: 10 May 2022 (04:45:21 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202205.0082.v1

Emotional Reaction to the First Dose of COVID-19 Vaccine: Post Vaccination Decline in Anxiety and Stress Among Anxious Individuals and Increase Among Individuals with Normal Anxiety Levels Pre Vaccination

Rasmieh Al-Amer, Malakeh Zuhdi Malak, Hala Mohammad Ramadan Burqan, Elena Stănculescu, Sylivia Nalubega, Abdulmajeed A. Alkhamees, Amin Omar Hendawy, Amira Mohammed Ali

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19, vaccine/vaccination; stress; anxiety; hesitancy; preparedness; Jordan/Arab

Online: 6 May 2022 (14:06:14 CEST)

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Although vaccinating the world is adopted by the WHO to limit COVID-19 transmission, people’s worries about vaccines may suppress their desire for vaccination despite vaccine availability. This study aimed to evaluate the levels of stress and anxiety among 250 Jordanians who received their first vaccine dose at a local community health center. The respondents completed the stress and anxiety subscales of the Depression Anxiety and Stress scale 21 (DASS-21) pre- and post-vaccination. The respondents expressed more moderate-severe levels of stress pre than post vaccination (20.8% and 13.2%, respectively). Meanwhile, 37.2% and 45.2% of the respondents expressed moderate-severe anxiety pre and post vaccination, respectively. Wilcoxon signed-rank test revealed that the drop in the level of stress from pre (median (IQR) = 5 (1-8)) to post vaccination (median (IQR) = 3 (1-7)) was statistically significant (z = -3.81, p = 0.001, r = 0.17) while the increase in anxiety was not. Anxiety median significantly dropped among individuals experiencing mild to severe anxiety pre vaccination. Similarly, stress and anxiety significantly increased among individuals expressing normal anxiety pre vaccination (z = -3.57 and -8.24, p values = 0.001, r = 0.16 and 0.37, respectively). Age positively correlated with post vaccination anxiety among respondents with mild pre vaccination anxiety, and it negatively correlated with pre vaccination level of stress in the normal anxiety group. Gender, marital status, respondents’ level of education, and history of COVID-19 infection had no significant correlation with anxiety or stress at either point of measurement. Overcoming their hesitancy to receive COVID-19 vaccine, individuals with normal levels of anxiety experienced a rise in their distress symptoms following immunization. On the contrary, vaccination seemed to desensitize anxious individuals. Policymakers need to formulate a population-specific plan to increase vaccine preparedness and promote psychological well-being over all during the pandemic.

Preprint ARTICLE | doi:10.20944/preprints202204.0314.v1

The Coronavirus Disease 2019 Spatial Care Path: Home, Community, and Emergency Diagnostic Portals

Gerald J. Kost

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Emergency Use Authorization; endemic; false omission; false omission rate; home testing; point-of-care testing (POCT); positive predictive value geometric mean-squared; prevalence boundary; recursive protocol; tier; visual logistics

Online: 30 April 2022 (08:42:08 CEST)

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Preprint REVIEW | doi:10.20944/preprints202204.0118.v1

SARS-CoV-2-Infection (COVID-19): Clinical Course and Cause(s) of Death

Giuliano Ramadori

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2-infection; dehydration; hypoalbuminemia; pulmonary hypoxia; hyaline memrane; pulmonary engorgement; lung weight; acute respiratory distress syndrome; diffuse alveolar damage (DAD)

Online: 13 April 2022 (08:27:30 CEST)

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ABSTRACT Two years after first patients approached the emergency rooms of hospitals in Wuhan becouse of respiratory distress,thousend of SARS-CoV-2 infected persons continue to die every day worldwide.SARS-CoV-2-infected patients undergo a process of dehydration and malnutrition before they develop respiratory problems and approach the emergency room of a hospital.This is,in many cases, the consequence of high fever which causes massive loss of fluids. In addition loss of appetite, is responsible for the deficit of protein intake.Most of the virus-infected patients admitted to the emergency room are therefore hypovolemic and hypoproteinemic and suffer of respiratory distress accompanied by ground grass opacities at CT-scan of the lungs.Critically ill patients are treated following the guidelines for treatment of septic shock but with „conservative“ fluid replacement and administration of diuretics to assure sufficient hourly urine production. The combination of conservative fluid administration with reduced protein content in the enterally administered diet, together with administration of diuretics, has severe hemodynamic consequenses in mostly aged,dehydrated,critically ill patients. Many of them will develop acute kidney injury in the next 24 hours.In most of the cases, patients continue to loose weight by loosing skeletal muscle mass. Ischemic damage in the lung capillaries is responsible for the acute respiratory distreass syndrome (ARDS) and for the hallmark of autoptic findings,diffuse alveolar damage (DAD) characterized by hyaline membrane formation,fluid invasion of the alveoli recruitment of some inflammatory cells and progressive arrest of blood flow in the pulmonary vessels.The consequence is progressive congestion , increase of lung weight and progressive hypoxia (progressive severity of ARDS).Sequestration of blood in the lungs worsen hypovolemia and ischemia in different organs.This is most probably responsible for recruitment of inflammatory cells and for persistance of elevated serum levels of positive acute-phase markers and of hypoalbuminemia. Autoptic studies have been performed mostly in patients who died in the ICU after SARS-CoV-2-infection because of progessive ARDS.In those patients, tubulus epithelium necrosis in the kidney is a frequent finding as it has been the case in the first SARS-CoV-1 pandemic.In the death certification charts, many times weeks after first symptoms have started ,cardiac arrest is the cause of death after respitatory insufficiency.Replacement therapy with sufficient amount of fluid and albumin should be part of the early individualized life-saving supportive measures avoiding mechanical ventilation.

Preprint REVIEW | doi:10.20944/preprints202204.0078.v1

Big Data in Laboratory Medicine – Ready for AI?

Tobias Blatter, Harald Witte, Upal Nath, Filippo Franchini, Alexander Benedikt Leichtle

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: digitalization; clinical chemistry; artificial intelligence; interoperability; FAIRification

Online: 8 April 2022 (10:52:31 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202203.0360.v1

Development of A Novel Anti-Epcam Monoclonal Antibody for Various Applications

Guanjie Li, Hiroyuki Suzuki, Teizo Asano, Tomohiro Tanaka, Hiroyoshi Suzuki, Mika K Kaneko, Yukinari Kato

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: EpCAM; monoclonal antibody; recombinant antibody; colorectal carcinoma

Online: 28 March 2022 (10:11:34 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202203.0323.v1

ApoA1 Deficiency Reshapes the Phenotypic and Molecular Characteristics of Bone Marrow Adipocytes in Mice

Afroditi Kastrenopoulou, Kyriakos Kypreos, Nicholaos Papachristou, Stavros Georgopoulos, Ioulia Mastora, Ioanna Papadimitriou-Olivgeri, Argyro Spentzopoulou, Dragana Nikitovic, Vassilios Kontogeorgakos, Harry C. Blair, Dionysios J. Papachristou

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Apolipoprotein A-1; High-density lipoprotein; Brown adipose tissue; White adipose tissue; Beige (Hybrid) adipose tissue

Online: 24 March 2022 (05:26:34 CET)

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Preprint REVIEW | doi:10.20944/preprints202203.0301.v1

Acute Heart Failure, 90-day Mortality—and Gravitational Ischemia in the Brain

J. Howard Jaster, Giulia Ottaviani

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Heart Failure; Gravity; Ischemia; Brain

Online: 22 March 2022 (12:38:29 CET)

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During the 90 days following hospitalization for acute heart failure, ejection fraction and type of discharge medications have been shown in clinical trials to have little effect on mortality. We examined the recent literature addressing brain-related etiologies of sudden death following heart failure. Two mechanisms of sudden unexpected death have been suggested to possibly result from 4 significant influences on pathophysiology in the brain. The two causes of death are severe cardiac arrhythmia, and neurogenic pulmonary edema. They are both mediated through the brainstem autonomic nuclei generally, and executed specifically through the dorsal motor nucleus of the vagus nerve. The four significant influences on pathophysiology in the brainstem autonomic nuclei are: 1) Hyper-stimulation of neurons in the solitary tract nucleus, increasing their metabolic requirements; 2) Inadequate blood flow at a vascular watershed terminus; 3) Additionally decreased blood flow following vasoconstriction related to relative hyperventilation and decreased pCO2 levels; 4) Gravitational ischemia in the brain—caused by the weight of the brain mass sitting above the brainstem. Changes in head tilt release gravitational ischemia in the brain. There is no specific head position (relative to gravity) that is considered favorable or unfavorable for an extended period of time (i.e. more than 24 hours). Even a small degree of head elevation, used in managing pulmonary congestion, may increase gravitational ischemia in the posterior fossa and brainstem. In this paper we suggest a new and important research avenue for intervening in cardiac arrhythmias, and preventing their occurrence, through the non-invasive use of head-tilting, and other head repositioning maneuvers. This could potentially help many geriatric patients with heart failure, who have decreased mobility in bed, and who tend to stay in one position longer, thereby increasing gravitational ischemia in the brain.

Preprint ARTICLE | doi:10.20944/preprints202203.0169.v1

Vaccines Associated Cardiac Adverse Events, including SARS-CoV-2 Myocarditis, Elevated Histamine Etiology Hypothesis

Darrell Ricke

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: COVID-19; adverse events; histamine intolerance; myocarditis; pericarditis; tachycardia

Online: 11 March 2022 (12:07:26 CET)

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Preprint COMMUNICATION | doi:10.20944/preprints202203.0162.v1

Taking a Closer Look: Clinical and Histopathological Characteristics of Culture-Positive versus Culture-Negative Pulmonary Mucormycosis

Amy Spallone, Cesar A Moran, Sebastian Wurster, Dierdre B Axell-House, Dimitrios P. Kontoyiannis

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Mucorales; pulmonary mucormycosis; hematologic malignancy; transplantation; fungal culture; histopathology

Online: 11 March 2022 (07:59:01 CET)

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Preprint ARTICLE | doi:10.20944/preprints202202.0347.v1

Fibrin Strands Will Grow from Soluble Fibrin and Hang Up In an ex vivo Microcirculatory Viscoelastic Model: Is This a Major Cause of Covid-19 Associated Coagulopathy?

Brian S. Bull, Karen L. Hay, Paul C. Herrmann

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Covid-19; fibrin; fibrinogen; fibrinolysis; fibrinolytic shutdown; rotational thromboelastometry (ROTEM); soluble fibrin monomer complex (SFMC); thromboelastography (TEG); thrombosis; viscoelastic

Online: 28 February 2022 (06:58:20 CET)

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Preprint ARTICLE | doi:10.20944/preprints202202.0329.v1

Microfluidic Microcirculation Mimetic as a Tool for the Study of Rheological Characteristics of Red Cells in Patients With Sickle Cell Anaemia

Marcus Inyama Asuquo, Emmanuel Effa, Oluwabukola Gbotosho, Akaninyene Otu, Nicole Tofner, Ameh Soter, Bhayankaram Sruti-Prathivadhi, Noah Zetocha, Chisom Nwakama, William Ohobu Egbe, Jochen Guck, Andrew E. Ekpenyong

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Sickle cell disorder; vaso-occlusive crisis; hydroxyurea; microcirculation; microfluidics; personalized medicine; deformation; transit time.

Online: 25 February 2022 (09:30:03 CET)

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Preprint REVIEW | doi:10.20944/preprints202201.0303.v1

NF-κB Signaling and Inflammation – Drug Repurposing to Treat Inflammatory Disorders?

Annabell Roberti, Laura Elizabeth Chaffey, David R Greaves

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Inflammation; NF-κB; drug repurposing; drug development; autoimmunity; COVID-19; multiple sclerosis; rheumatoid arthritis

Online: 20 January 2022 (11:16:25 CET)

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Preprint ARTICLE | doi:10.20944/preprints202201.0162.v1

Possible Role of the Antibiotic-Modified Microbiome in the Development of Hematological Malignancies in European Countries

Gábor Ternák, Károly Berényi, Balázs Németh, Ágnes Szenczi, István Kiss

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: antibiotic cnsumtion; microbiome; hematological malignancies; Hodgkin-lymphoma (HL); Non-Hodgkin lymphoma (NH); multiplex myeloma (MM); leukemia (LEU)

Online: 12 January 2022 (12:53:22 CET)

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Hematological malignancies are considered the fifth most common cancer in the world. Several risk factors and probable etiological agents have been suspected in the pathomechanism of those malignancies as infections, chemicals, irradiation, etc., and recently, the contribution of the altered gut flora, dysbiosis, was identified also as a possible additional factor to the existing ones. Host, and external factors, like antibiotics, which were identified as a major disruptor of the "normal" gut flora, influence the composition of the microbiome. Considering the several-fold differences in antibiotic consumption patterns and the incidence of hematological malignancies in European countries, the hypothesis was raised that the dominant consumption of certain antibiotic classes might influence the incidence of different hematological malignancies through the modification of gut flora. Comparisons were performed between the average antibiotic consumption databases reported yearly by ECDC (2009-2019) and the incidence rate of Hodkin lymphoma (HL), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), and leukemia (LEU) estimated for 2020 in 30 European countries. Applying Spearman calculations, significant positive correlation has been found between the incidence of HL and tetracycline (J01A) consumption (r = 0.399, p = 0,029), NHL and narrow spectrum, beta-lactamase resistant penicillin (J01CF) (r = 0.580, p = 0,001), MM and tetracycline (r = 0.492, p = 0.006), penicillin (J01C) (r = 0.366, p = 0.047), narrow spectrum, beta-lactamase resistant penicillin (J01CF) (r = 0.574, p = 0.001), while strong, significant negative correlation has been recorded between NHL and cephalosporin (r = -0,460, p = 0,011), and quinolone (r = -0,380, p = 0,038). The incidence of LEU did not show any positive or negative association with any antibiotic classes. It is concluded that certain antibiotic classes, in addition to other putative factors, might promote or inhibit the development of different hematological malignancies.

Preprint ARTICLE | doi:10.20944/preprints202201.0032.v1

Dysbiosis in Alzheimer’s Disease Might be Triggered by Certain Classes of Antibiotics with Time-lapse: New Insights in the Pathogenesis?

Gábor Ternák, Márton Németh, Martin Rozanovic, Lajos Bogár

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: antibiotic consumption; gut flora; dysbiosis; Alzheimer disease; dementia; gut-brain axis, mediator molecules

Online: 5 January 2022 (10:44:59 CET)

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Background and objectives: Alzheimer's disease (AD) is a progressive neurodegenerative illness, responsible for 60-70% of all dementias, affecting over 50 million people worldwide, and nearly 11 million in European countries. Several putative factors are identified in the literature as causative agents or risk factors for the development of AD. The amyloid cascade hypothesis has been the main hypothesis about the pathophysiology of AD for decades. Recent studies raised the possible role of dysbiosis in the development of AD which prevents memory loss. The amyloid-β (Aβ) deposition might be considered as an inflammatory reaction to certain molecular products arising from the altered microbiome. Based on the above observations, it has been suspected, that antibiotic consumption patterns of different antibiotic classes might be associated with the prevalence of AD in European countries. Methods: Antibiotic consumption (ECDC) for 1997-2007, 2008-2018, and as the whole 1997-2018 period, have been compared to the AD prevalence for 2018 expressed in percentage of the population and statistically analyzed by Pearson calculation. Results: A significant positive correlation has been found between the AD prevalence (2018) and the average quinolone consumption for the year 1997-2007 (p: 0.044). A similar association was not observed for the entire 22 years (1997-2018) of the average quinolone consumption, and the years 2008-18, indicating 10-20 years of time-lapse between the antibiotic exposure and the development of AD. The ratio of broad-spectrum and narrow-spectrum antibiotics (B/N) estimated in the ECDC database for the years of 2008-2018 showed a strong positive association with AD prevalence (2018) (p: 0.026) and a positive correlation tendency for the entire 22 years 1997-2018 (p: 0.063), but none for the years 1997-2007 (p: 0.241). Broad-spectrum, beta-lactamase sensitive penicillin (J01CA) consumption showed a positive (non-significant) correlation with the prevalence of AD for the years 2008-2018 (p:0.080).Discussion: Our study indicated the possible sequential role of certain classes of antibiotics in the development of dysbiosis leading to amyloid deposits of AD, which strengthen the possible role of different mediator molecules (short-chain fatty acids, lipopolysaccharides, etc.) produced by the altered microbiome in the development of AD.

Preprint ARTICLE | doi:10.20944/preprints202112.0473.v1

Fanconi Anemia Patients from an Indigenous Community in Mexico Carry a New Founder Pathogenic Variant in FANCG

Pedro Reyes, Benilde García-deTeresa, Ulises Juárez, Fernando Pérez-Villatoro, Moisés O Fiesco-Roa, Alfredo Rodríguez, Bertha Molina, Maria Teresa Villarreal-Molina, Jorge Melendez-Zajgla, Alessandra Carnevale, Leda Torres, Sara Frias

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Fanconi anemia; Chromosome instability; FANCG; splicing; founder pathogenic variant; Mixe indigenous group.

Online: 29 December 2021 (19:28:49 CET)

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Preprint ARTICLE | doi:10.20944/preprints202112.0453.v1

Detection of Novel Biomarkers in Saliva of Rheumatoid Arthritis Model Mice by Proteomics and Pathological Analysis

Wakako Sakaguchi, Juri Saruta, Shinya Fuchida, Yuko Yamamoto, Masahiro To, Tomoko Shimizu, Mayumi Yakeishi, Keiichi Tsukinoki

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: anti-citrullinated protein antibody (ACPA); alpha-1-antitrypsin (A1AT); DBA/1JJmsSlc mice Proteome analysis; rheumatoid arthritis (RA)

Online: 28 December 2021 (14:44:54 CET)

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Preprint REVIEW | doi:10.20944/preprints202112.0380.v1

Considerations and Challenges for Sex-Aware Drug Repurposing

Jennifer Fisher, Emma Jones, Victoria Flanary, Avery Williams, Elizabeth Ramsey, Brittany Lasseigne

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: sex differences; drug repurposing; sex-bias; sex-aware; review; therapeutics; pharmaceuticals; computational drug repurposing

Online: 23 December 2021 (10:31:25 CET)

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Sex differences are essential factors in disease etiology and manifestation in many diseases such as cardiovascular disease, cancer, and neurodegeneration (1). The biological influence of sex differences (including genomic, epigenetic, hormonal, immunological, and metabolic differences between males and females) and the lack of biomedical studies considering sex differences in their study design has led to several policies. For example, the National Institute of Health’s (NIH) sex as a biological variable (SABV) and Sex and Gender Equity in Research (SAGER)) policies to motivate researchers to consider sex differences (2). However, drug repurposing, a promising alternative to traditional drug discovery by identifying novel uses for FDA-approved drugs, lacks sex-aware methods that can improve the identification of drugs that have sex-specific responses (1,3–5). Sex-aware drug repurposing methods either select drug candidates that are more efficacious in one sex or deprioritize drug candidates based on if they are predicted to cause a sex-bias adverse event (SBAE), unintended therapeutic effects that are more likely to occur in one sex. Computational drug repurposing methods are encouraging approaches to develop for sex-aware drug repurposing because they can prioritize sex-specific drug candidates or SBAEs at lower cost and time than traditional drug discovery. Sex-aware methods currently exist for clinical, genomic, and transcriptomic information (3,6,7). They have not expanded to other data types, such as DNA variation, which has been beneficial in other drug repurposing methods that do not consider sex (8). Additionally, some sex-aware methods suffer from poorer performance because a disproportionate number of male and female samples are available to train computational methods (3). However, there is development potential for several different categories (i.e., data mining, ligand binding predictions, molecular associations, and networks). Low-dimensional representations of molecular association and network approaches are also especially promising candidates for future sex-aware drug repurposing methodologies because they reduce the multiple hypothesis testing burden and capture sex-specific variation better than the other methods (9,10). Here we review how sex influences drug response, the current state of drug repurposing including with respect to sex-bias drug response, and how model organism study design choices influence drug repurposing validation.

Preprint ARTICLE | doi:10.20944/preprints202112.0366.v1

An Integrated Epigenomic and Genomic View on Phyllodes and Phyllodes-Like Breast Tumors

Juergen Hench, Tatjana Vlajnic, Savas Deniz Soysal, Ellen C Obermann, Stephan Frank, Simone Muenst

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: fibroepithelial breast lesions; phyllodes tumors; methylation analysis; copy number alterations; dimension reduction; unsupervised machine learning

Online: 22 December 2021 (12:46:50 CET)

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Preprint REVIEW | doi:10.20944/preprints202112.0363.v1

Atypical Roles of the Chemokine Receptor ACKR3/CXCR7 in Platelet Pathophysiology

Madhumita Chatterjee

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Platelet; ACKR3/CXCR7; Thrombosis; Thrombo-inflammation; Anti-platelet therapy; Cardiovascular disease; Coronary artery disease

Online: 22 December 2021 (12:27:01 CET)

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Preprint ARTICLE | doi:10.20944/preprints202112.0350.v1

HMGB1 Inhibition to Ameliorate Organ Failure and Increase Survival in Trauma

Zhangsheng Yang, Milomir O Simovic, Peter R Edsall, Bin Liu, Tomas S Cancio, Andriy I Batchinsky, Leopoldo C Cancio, Yansong Li

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: HMGB1; trauma; hemorrhagic shock; inflammation; multiple organ failure

Online: 22 December 2021 (10:36:56 CET)

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Preprint BRIEF REPORT | doi:10.20944/preprints202112.0327.v1

Predicting and Visualizing STK11 Mutation in Lung Adenocarcinoma Histopathology Slides Using Deep Learning

Runyu Hong, Wenke Liu, David Fenyö

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: keyword; histopathology; deep learning; machine learning; cancer; lung adenocarcinoma; immune; computational pathology

Online: 21 December 2021 (12:28:44 CET)

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Preprint ARTICLE | doi:10.20944/preprints202112.0053.v1

Antibiotic Consumption Patterns in European Countries Might Be Associated with the Prevalence of Diabetes Type-1-2 (T1D, T2D)

Gábor Ternák, Márton Németh, Martin Rozanovic, Lajos Bogár

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: diabetes type-1; T1D; diabetes type-2; T2D; antibiotics; antibiotic classes; microbiome; dysbiosis; prevalence; concordance

Online: 3 December 2021 (12:45:23 CET)

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Abstract: Several publications have raised the issue that the development of diabetes is preceded by alteration of the microbiome (dysbiosis) and hence, the role of environmental factors, triggering dysbiosis, should be considered. Antibiotics are powerful agents inducing dysbiosis and the authors wanted to explore the possible relationship between the consumption of different major classes of antibiotics and the prevalence of diabetes (type-1, /T1D/, type-2 /T2D/) in thirty European countries. According to our hypothesis, if such association exists, the dominant use of certain major antibiotic classes might be reflected in the prevalence of T1D and T2D in different countries. Comparisons were performed between the prevalence of diabetes (T1D and T2D) estimated for 2019 and featured in the Diabetes Atlas with the average yearly consumption of major antibiotic classes of the previous 10 years (2010-19) extracted from the ECDC yearly reports on antibiotic consumption in Europe. Pearson correlation and variance analysis were used to estimate the possible relationship. Strong, positive (enhancer) associations were found between the prevalence of T1D and the consumption of tetracycline (J01A /p: 0.001/) and the narrow spectrum penicillin (J01CE /p: 0,006/, CF /p: 0.018/). Strong negative (inhibitor) association was observed with broad-spectrum, beta-lactamase resistant penicillin (J01CR /p: 0.003/), macrolide (J01F /p: 0.008/) and quinolone (J01M /p: 0.001/). T2D showed significant positive associations with cephalosporin (J01D /p: 0.048/) and quinolone (J01M /p: 0.025/), and a non-significant negative association was detected with broad-spectrum, beta-lactamase-sensitive penicillin (J01CA /p: 0.67/). Countries with the highest prevalence of diabetes (first 10 positions) showed concordance with the higher consumption of “enhancer” and the lower consumption of “inhibitor” antibiotics (first 10 positions) as indicated by variance analysis. Countries with high prevalence of T1D showed high consumption of tetracycline (p: 0.015), and narrow spectrum, beta-lactamase sensitive penicillin (p: 0.008), and low consumption of “inhibitor” antibiotics (broad-spectrum, beta-lactamase resistant, combination penicillin (p: 0.005), cephalosporin (p: 0.036), and quinolone (p: 0.003). Countries with a high prevalence of T2D consumed more cephalosporin (p: 0.084), quinolone (p: 0.54), and less broad-spectrum, beta-lactamase sensitive penicillin (p: 0.012) than other countries. Conclusion/Interpretation: The development of diabetes-related dysbiosis might be attached to higher consumption of specific classes of antibiotics, showing positive (enhancer) associations with the prevalence of diabetes, and the low consumption of other classes of antibiotics shoving negative (inhibitory) associations. Those groups of antibiotics are different in T1D and T2D

Preprint ARTICLE | doi:10.20944/preprints202111.0478.v1

You + ME Registry: A Research Platform to Facilitate Clinical and Therapeutic Discoveries in ME/CFS and Related Diseases

Allison Ramiller, Kathleen Mudie, Elle Seibert, Sadie Whittaker

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Long COVID; data acquisition source; post-infectious; longitudinal cohort study; patient-powered

Online: 25 November 2021 (13:51:54 CET)

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Preprint ARTICLE | doi:10.20944/preprints202111.0330.v1

Evaluation of B-Cell Kinetics After Acellular Pertussis Vaccination in Four Cohorts of Different Age and Priming Background

Annieck M Diks, Pauline Versteegen, Cristina Teodosio, Rick J Groenland, Bas de Mooij, Anne-Marie Buisman, Alba Torres-Valle, Martín Pérez-Andrés, Alberto Orfao, Guy A.M. Berbers, Jacques J.M. van Dongen, Magdalena A. Berkowska

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Tdap; flow cytometry; acellular pertussis vaccine; whole cell pertussis vaccine; plasma cells

Online: 18 November 2021 (14:18:35 CET)

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Preprint ARTICLE | doi:10.20944/preprints202111.0313.v1

PRDX6 Alleviates Lipopolysaccharide-Induced Inflammation in Human Gingival Fibroblasts by Regulation of NRF2

Wen-ying Yang, Xiang Meng, Yue-rong Wang, Qing-qing Wang, Xin He, Xiao-yu Sun, Nan Cheng, Lei Zhang

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: PRDX6; inflammation; NRF2; HGFs.

Online: 17 November 2021 (23:34:15 CET)

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Preprint ARTICLE | doi:10.20944/preprints202111.0309.v1

Transcriptional Analysis-Based Alterations Affecting Neuritogenesis of the Peripheral Nervous System in Psoriasis

Dóra Romhányi, Kornélia Szabó, Lajos Kemény, Endre Sebestyén, Gergely Groma

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: psoriasis; cutaneous nervous system; axon development; myelination

Online: 17 November 2021 (12:54:23 CET)

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Medicine and Pharmacology