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Preprint REVIEW | doi:10.20944/preprints202409.2091.v1

Diagnostic Accuracy of Specific IgE to Lipid Transfer Proteins (LTPs) in Food Allergy: A Systematic Review

Chiara Bellia, Davide Stefano Sardina, Concetta Scazzone, Domenico Lio, Letizia Scola, Carina Gabriela Uasuf

Subject: Immunology And Allergy, Medicine And Pharmacology Keywords: food hypersensitivity; lipid transfer protein; IgE; component resolved diagnosis

Online: 26 September 2024 (17:08:49 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.2089.v1

Exploring the Impact of IL-33 Gene Polymorphism (rs1929992) on Susceptibility to Chronic Urticaria and its Association with Serum Interleukin-33 levels

Carmen-Teodora Dobrican-Băruța, Diana Mihaela Deleanu, Mihaela Iancu, Ioana Adriana Muntean, Irena Nedelea, Radu-Gheorghe Bălan, Lucia Maria Procopciuc, Gabriela Adriana Filip

Subject: Immunology And Allergy, Medicine And Pharmacology Keywords: chronic urticaria; genetic polymorphisms; IL-33; SNP rs1929992; cytokine; autoimmune; susceptibility

Online: 26 September 2024 (17:07:22 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202409.2145.v1

Eczematous Adverse Drug Reaction after Selpercatinib Treatment: Case Report

Bingrun Li, Peng Cao, Wenjing Xu, Litao Zhang

Subject: Dermatology, Medicine And Pharmacology Keywords: eczematous reaction; adverse drug reaction; selective RET inhibitor; Selpercatinib; glucocorticoid

Online: 26 September 2024 (16:44:59 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.2151.v1

Adverse Effects of Aβ1-42 Oligomers: Impaired Contextual Memory and Altered Intrinsic Properties of CA1 Pyramidal Neurons

Min Kaung-Wint-Mon, Hiroyuki Kida, Itsuki Kanehisa, Masahiko Kurose, Junko Ishikawa, Yuya Sakimoto, Paw-Min Thein-Oo, Ryoichi Kimura, Dai Mitsushima

Subject: Neuroscience And Neurology, Medicine And Pharmacology Keywords: Aβ1-42 oligomers; contextual memory; intrinsic properties; neuronal hyperexcitability; riluzole; lecanemab

Online: 26 September 2024 (16:40:28 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.2142.v1

Impact of Intensive Insulin Stabilisation Service in Pregnancy with Type 1 Diabetes

Stephanie Teasdale, Natasha Cannon, Alison Griffin, Janelle Nisbet, David Mcintyre

Subject: Endocrinology And Metabolism, Medicine And Pharmacology Keywords: type 1 diabetes; pregnancy; continuous glucose monitoring; glycemic variability; glycemic control

Online: 26 September 2024 (16:30:48 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.2147.v1

Relationship between Dietary Nutrient Intake and Autophagy–Related Genes in Obese Humans. A Narrative Review

Martyna Bednarczyk, Nicola Dąbrowska-Szeja, Dariusz Łętowski, Dariusz Waniczek, Sylwia Dzięgielewska-Gęsiak, Małgorzata Muc-Wierzgoń

Subject: Dietetics And Nutrition, Medicine And Pharmacology Keywords: nutrients; dietary intake; autophagy; overweight; obesity; humans

Online: 26 September 2024 (16:29:23 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.2140.v1

Depression in the Elderly Population: A More Serious Problem Than Perceived and Its Impact on Geriatric Rehabilitation Outcomes – A Study from Switzerland

Bojan Miletic, Lejla Jelovica, Udo Courteney, Silvije Segulja

Subject: Other, Medicine And Pharmacology Keywords: depression; elderly; functional status; outcome; rehabilitation

Online: 26 September 2024 (16:13:26 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.2148.v1

Progress of IL-12 in Tumor Immunotherapy

Qing He, Chunyan Dong, Dejiang Tan, Huimin Sun, Zhuang Li, Yiyang Zheng, Linyu Zhang, Sihan Liu, Yu Zhang

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: IL-12; Immunotherapy; Delivery system

Online: 26 September 2024 (16:10:41 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202409.2133.v1

Post-Transplantation B-Cell Lymphoproliferative Disorder in a Dual Organ Recipient: A Rare Case Report and Literature Review

Vidna Karadžić Ristanović, Jelena Pavlović, Voin Brković, Ana Bontić, Marko Baralić, Marija Milinković, Milica Kravljača, Dragan Vasin, Maja Životić, Darko Antić, Vojin Vuković, Milan Radović

Subject: Transplantation, Medicine And Pharmacology Keywords: lymphoproliferative disorders; kidney transplantation; b-cell lymphoma

Online: 26 September 2024 (15:58:57 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.2108.v1

Sustainable Biomaterials for Pharmaceutical and Medical Applications

Induni Nayodhara Weerarathna, PRAVEEN KUMAR, Anurag Luharia, Gaurav Mishra

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: Sustainable Biomaterials; Pharmaceutical Applications; Medical Applications; Bio-material Fundamentals; Sustainability

Online: 26 September 2024 (14:59:07 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.2116.v1

Low-Dose Creatine Supplementation May Be Effective in Early-Stage Statin Myopathy: An Observational, Preliminary Study

Elena Scarsi, Ulrico Dorighi, Enrico Adriano, Marina Grandis, Maurizio Balestrino

Subject: Clinical Medicine, Medicine And Pharmacology Keywords: creatine; statin; myopathy; therapy

Online: 26 September 2024 (14:51:47 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.2098.v1

Pediatric Meningeal Diseases: What Radiologists Need to Know

Dhrumil Deveshkumar Patel, Laura Z. Fenton, Swastika Lamture, Vinay Kandula

Subject: Pediatrics, Perinatology And Child Health, Medicine And Pharmacology Keywords: Meningeal enhancement; Pediatric; Meningitis; Drop Metastasis; Pachymeningeal enhancement

Online: 26 September 2024 (14:00:25 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.2045.v1

Molecular Pathway and Immune Profile Analysis of IPMN-Derived versus PanIN-Derived Pancreatic Ductal Adenocarcinomas

Margaret A Park, Kristyn Gumpper-Fedus, Somashekar G. Krishna, Maria C. Genilo-Delgado, Stephen Brantley, Phil A. Hart, Mary E. Dillhoff, Maria F. Gomez, Toni L. Basinski, Shaffer R. Mok, Anjuli K. Luthra, Jason B. Fleming, Amir Mohammadi, Barbara A Centeno, Kun Jiang, Alexandra Karolak, Daniel Jeong, Dung-Tsa Chen, Paul Stewart, Jamie K. Teer, Zobeida Cruz-Monserrate, Jennifer B. Permuth

Subject: Oncology And Oncogenics, Medicine And Pharmacology Keywords: pancreatic ductal adenocarcinoma; IPMN; PanIN; transcriptomics

Online: 26 September 2024 (13:47:14 CEST)

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Introduction: Intraductal papillary mucinous neoplasms (IPMN) are commonly-detected pancreatic cysts that may transform into pancreatic ductal adenocarcinoma (PDAC). Predicting which IPMNs will progress to PDAC remains a clinical challenge. Moreover, identifying those clinically evident IPMNs for which a surveillance approach is best is a dire clinical need. Therefore, we aimed to identify molecular signatures that distinguished between PDAC with and without clinical evidence of a IPMN to identify novel molecular pathways related to IPMN-derived PDAC that could help guide biomarker development. Methods: Data from the Oncology Research Information Exchange Network (ORIEN) multi-institute sequencing project was utilized to analyze 66 PDAC cases from Moffitt Cancer Center and The Ohio State University Wexner Medical Center for which tumor whole transcriptome sequencing datasets were generated. Cases were classified based on whether a tumor had originated from an IPMN (n=16) or presumably through the pancreatic intraepithelial neoplasia (PanIN) pathway (n=50). We then performed differential expression and pathway analysis using Gene-Set Enrichment Analysis (GSEA) and Pathway Analysis with Downweighted Genes (PADOG) algorithms. We also analyzed immune profiles using the Tumor-immune Microenvironment Deconvolution Web-portal for Bulk Transcriptomics (TIMEx). Results: Both GSEA and TIMEx indicate that PanIN-derived PDAC tumors enrich inflammatory pathways (complement, hedgehog signaling, coagulation, inflammatory response, apical surface, IL-2/STAT5, IL-6/STAT3, EMT, KRAS signaling, apical junction, IFN-gamma, allograft rejection) and are comparatively richer in almost all immune cell types than those from IPMN-derived PDAC upon deconvolution. IPMN-derived tumors were enriched in metabolic and energy generating pathways (oxidative phosphorylation, unfolded protein response, pancreas beta cells, adipogenesis, fatty acid metabolism, protein secretion). Further, the metabolic-linked gene signature enriched in the IPMNderived samples is associated with a cluster of early stage and long survival (top 4th quartile) PDAC cases from the Cancer Genome Atlas (TCGA) expression database. Intriguingly, the gene most significantly upregulated for both the improved survival group and IPMN-derived PDAC was gastrokine-2 (GKN2, padj<0.001), a gene upregulated in PDAC precursor lesions (compared to PDAC). Conclusions: Our data suggest that IPMN-derived and PanIN-derived PDACs differ in the expression of immune profiles and metabolic pathways. These initial findings support future studies to assess the accuracy of identifying PDACs arising from IPMN lesions based on either GKN2 expression or their metabolic or immune profiles and explore mechanisms to explain these findings.

Preprint REVIEW | doi:10.20944/preprints202409.2122.v1

What Do We Know about the Relationship between Lycopene and Metabolic Diseases? Review

Anna Kulawik, Judyta Cielecka-Piontek, Bogusław Czerny, Adam Kamiński, Przemysław Zalewski

Subject: Pharmacy, Medicine And Pharmacology Keywords: lycopene; metabolic syndrome; obesity; type 2 diabetes

Online: 26 September 2024 (12:13:48 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.2086.v1

Neurotensin and Its Involvement in Female Hormone-Sensitive Cancers

Ninon Bertrand, Romane Mougel, George Riley, Marie Bruand, Guillaume GAUCHOTTE, Mikaël Agopiantz

Subject: Oncology And Oncogenics, Medicine And Pharmacology Keywords: neurotensin; breast cancer; ovarian cancer; endometrial cancer

Online: 26 September 2024 (11:33:49 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.2100.v1

The Impact of Virtual Reality as a Rehabilitation Method using TRAVEE system on Functional Outcomes, and Disability in Stroke Patients: A Pilot Study

Potcovaru Claudia-Gabriela, Delia Cinteză, Miruna Ioana Sandulescu, Daniela Poenaru, Ovidiu Chiriac, Cristian Lambru, Alin Moldoveanu, Ana Magdalena Anghel, Mihai Berteanu

Subject: Neuroscience And Neurology, Medicine And Pharmacology Keywords: motor impairment; upper limb rehabilitation; disability assessment; WHODAS 2.0; virtual reality; conventional rehabilitation therapy

Online: 26 September 2024 (10:53:15 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.2090.v1

The Predictive Impact of Antipsychotics on Functionality Index in Schizophrenia (PIAF)

Gabriel Cristian Marinescu, Petru Iulian Ifteni, Andreea Teodorescu, Radu Georgescu

Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: schizophrenia; antipsychotics; functionality; LAI

Online: 26 September 2024 (09:59:15 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.2096.v1

Translational Proofs on Bee Pollen as a Source of Biopharmaceuticals for Neurodegeneration and Cancer Research: A Scoping Review and Prospective Reflections

Rachid Kacemi, Maria Graça Campos

Subject: Pharmacy, Medicine And Pharmacology Keywords: aging; apoptosis; autophagy; bee pollen; cancer; epigenetics; ferroptosis; human microbiota; inflammation; neurodegeneration; oxidative stress; polyphenols

Online: 26 September 2024 (09:56:37 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.2073.v1

Comparative Analysis of Shear Bond Strength in Orthodontic Brackets between Milled and 3D-Printed Definitive CAD-CAM Restorations

Mohammad Aldosari, Noha M Anany, Razan Alaqeely, Jawaher Alsenaidi, Aref Sufyan, Sameh Talaat, Christoph Bourauel, Tarek M Elshazly, Abdulaziz Alhotan

Subject: Dentistry And Oral Surgery, Medicine And Pharmacology Keywords: Dentistry; Orthodontics; Biomechanics; Cementation; Brackets; Thermocycling; Aging

Online: 26 September 2024 (09:55:39 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.2064.v1

Unraveling the Omega-3 Puzzle: Navigating Challenges and Innovations for Bone Health and Healthy Aging

Zayana Ali, Mohammad A. Al-Ghouti, Haissam Abou-Saleh, Md Mizanur Rahman

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: Omega-3 polyunsaturated fatty acids; Eicosapentaenoic acid (EPA); ; Docosahexaenoic acid (DHA); ; Bone health; Aging; Bioavailability; Nanoparticle encapsulation; specialized proresolving mediators (SPM)

Online: 26 September 2024 (09:55:10 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.2075.v1

Development of a Herb-Based Dietary Ingredient with Potential Nootropic Properties: From Bench to Bedside

Pau Navarro, Justyna Meissner, José L. Mullor, Nuria Caturla, Jonathan Jones

Subject: Dietetics And Nutrition, Medicine And Pharmacology Keywords: nootropic; memory; brain health; salvia officinalis; rutin

Online: 26 September 2024 (09:22:03 CEST)

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Brain health is a matter of great importance as we age, where memory loss and other cognitive declines become slowly apparent. There are numerous natural solutions, called nootropics, that can help mitigate this natural process. While some, such as ginkgo biloba, have been traditionally used for centuries, in many cases there is a lack of scientific evidence on their potential mechanisms and efficacy. To this end, the objective of the current study is to evaluate and compare several standardized herb extracts with potential nootropic effects, and from this analysis develop a formula and confirm its effect in healthy volunteers with mild cognitive impairment. A total of 9 standardized herb extracts were chosen based on previous scientific evidence and tested in human neural stem cell cultures exposed to oxidative stress. The expression of nerve growth factor (NGF), NRF2 and vascular endothelial growth factor (VEGF) were also analyzed. As a result, it was observed that an extract from Salvia officinalis revealed to have the most noticeable effect among the herbs analyzed. In further tests it was confirmed that its combination with rutin, a phenolic compound with potential nootropic effects, increased brain derived neurotrophic factor (BDNF) expression, as well as inhibiting acetylcholine esterase (AChE) activity. Finally, a randomized, double-blind placebo-controlled clinical study was conducted, testing the effects of the combination at two different doses, for 12 weeks, in healthy volunteers aged 50+ with mild cognitive impairment. Two questionnaires were applied, the MoCA and ADAS-Cog. As a result, both doses significantly improved several characteristics related to memory, particularly memory recall, with a more noticeable effect in the higher dose. Therefore, the results suggest that the long-term intake, at least 6-12 weeks, of a natural herb blend comprised of Salvia officinalis and rutin can help improve certain brain health-related parameters in healthy subjects with mild cognitive impairment.

Preprint ARTICLE | doi:10.20944/preprints202409.1794.v2

Sensor-acquired Reachable Workspace (RWS) Correlates with Activities of Daily Living (ADL) Function in Stroke as Measured by Functional Independence Measure (FIM) Self-Care

Vicky Chan, Seungcheol Austin Lee, Jaylen M Lee, Jay J Han

Subject: Clinical Medicine, Medicine And Pharmacology Keywords: Stroke; Reachable Workspace; Upper Extremity; Activities of Daily Living; Function

Online: 26 September 2024 (09:21:17 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.2062.v1

Survival Determinants in Glioblastoma: An Insight into Biopsy-Only Patient Outcomes

João Meira Gonçalves, Francisca Ferreira, Bruno Carvalho, Patrícia Polónia, Paulo Linhares

Subject: Oncology And Oncogenics, Medicine And Pharmacology Keywords: Glioblastoma; IDH-wildtype; Biopsy-only survival; Prognostic factors

Online: 26 September 2024 (09:16:19 CEST)

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Glioblastoma is a challenge in neuro-oncology, with survival significantly influenced mainly by extent of resection and molecular markers. Despite advancements, the prognosis for IDH-wildtype glioblastoma remains poor, particularly when surgical resection is not possible. However, some patients exhibit unexpectedly extended survival despite the extent of resection. This study aims to analyze the determinants that contribute to these atypical survival rates among glioblastoma patients who have had solely biopsy procedures. We conducted a retrospective analysis of patients diagnosed with IDH- wildtype glioblastomas at our institution from 2017 to 2021, who underwent biopsy only. The study focused on evaluating the impact of demographic characteristics, clinical features, molecular markers and treatment modalities on survival outcomes (Overall Survival (OS) and Progression-Free Survival (PFS)). Statistical analyses included survival analysis and logistic regression for evaluating associations between OS and preoperative characteristics and postoperative treatments. The cohort included 99 patients, with a median age at diagnosis of 65.5 years. Median OS and PFS were 6.0 and 3.6 months, respectively. The multivariate analysis revealed that higher KPS scores before biopsy, no contrast uptake on imaging and any adjuvant therapy, particularly the use of bevacizumab, were independently associated to increased OS (HR=0.97, p=0.009. HR=0.7, p=0.015; HR=0.27, p=0.002, respectively). Out of 99 patients, 77.8% survived past the 3-month threshold, with 87.0% of this receiving adjuvant treatment. Only 8% of patients survived past 24 months, and in this group of patients, MGMT Methylation was observed in just 25% of cases. Kaplan-Meier analysis indicated a better prognosis with any type of adjuvant therapy across all patients, particularly so in those with KPS ≥70. Age did not significantly affect survival outcomes (OR=1.00, p=0.835). Our findings reveal that any adjuvant treatment, no contrast uptake on imaging and higher preoperative KPS are key determinants of survival in IDH wildtype glioblastoma and should therefore be considered when deciding whether to perform a biopsy.

Preprint REVIEW | doi:10.20944/preprints202409.2055.v1

Virtual Reality and Artificial Intelligence Paving the Future of Cardiac Interventions and Training, a Review of the Available Reviews

Antoine AbdelMassih, Abdullah Nasser, Gawahir AbdelRahman, Lama Mkarem, Mariam AbuShashieh, Rahaf AbuGhosh

Subject: Cardiac And Cardiovascular Systems, Medicine And Pharmacology Keywords: Cardiac care; cardiac interventions; artificial intelligence, virtual reality; visual spatial ability

Online: 26 September 2024 (09:12:37 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.2041.v1

Research Collaboration in Viral Hepatitis: A Network Analysis of 60,720 Publications over Two Decades

Naruaki Ogasawara

Subject: Gastroenterology And Hepatology, Medicine And Pharmacology Keywords: gastroenterology; viral hepatitis; co‐authorship network analysis; network analysis; research collaboration; research trend analysis; research trends; key researchers; research strategies; internal medicine; planning future collaborative studies

Online: 26 September 2024 (09:04:05 CEST)

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Aim: This study aims to analyze the structure of the co-authorship network in viral hepatitis research from 2000 to 2023 using data from the Web of Science (WoS) Core Collection. The objective is to identify key researchers, evaluate the collaborative dynamics, and understand the evolution of scientific contributions in this field. Method: This study utilized network analysis techniques to evaluate 60,720 publications related to viral hepatitis research indexed in the WoS Core Collection between 2000 and 2023. The analysis was conducted using Python (Version 3.10.5) in the PyCharm development environment (Software Version 2022.1.3). The co-authorship networks were assessed using macro-level indicators such as network density (the ratio of actual to possible connections), clustering coefficient (degree of node clustering), number of components (distinct connected subgroups), and average path length (average distance between nodes). Micro-level indicators including degree centrality (importance based on the number of connections), closeness centrality (proximity to other nodes), and betweenness centrality (frequency of a node on the shortest paths between others) were also analyzed.Result: The findings reveal that the viral hepatitis research network is characterized by low network density, indicating sparse overall collaboration. However, the clustering coefficient is high, suggesting strong collaborations within small, cohesive groups. Over the years, researchers such as Stefan Zeuzem, Maria Buti, and Fabien Zoulim have played pivotal roles, serving as central figures in the network. A noticeable increase in network density and clustering from 2020-2023 suggests growing collaboration in recent years.Conclusion: This study underscores the importance of international collaboration in advancing viral hepatitis research. Key researchers have emerged as influential contributors, facilitating global research activities. Network analysis provides valuable insight into the structure of these collaborations and helps identify potential areas for future research and partnerships to combat viral hepatitis globally. The results of this study should be used to reduce global healthcare disparities, promote research collaboration, and address viral hepatitis as a global public health problem.

Preprint REVIEW | doi:10.20944/preprints202409.2038.v1

Bioactive and Its Chondroprotective Effects in Ameliorating Osteoarthritis: A Focus on Nanoparticle Therapy

Kota Sri Naga Hridayanka, Asim K. Duttaroy, Sanjay Basak*

Subject: Dietetics And Nutrition, Medicine And Pharmacology Keywords: Bioactive; Polyphenol; Nanocurcumin; Epigenome; Nanoformulation; Non-coding RNA; Gut microbiota; Chondrocyte; Osteoarthritis

Online: 26 September 2024 (03:59:25 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1977.v1

Pharmacokinetic Analysis of the Bioavailability of AQUATURM®, a Water-Soluble Curcumin Formulation in Comparison to a Conventional Curcumin Tablet, in Human Subjects

Gerald Muench

Subject: Pharmacology And Toxicology, Medicine And Pharmacology Keywords: water-soluble curcumin; pharmacokinetics; plasma; curcuminoids; area under the curve; bioavailability

Online: 25 September 2024 (17:55:38 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1946.v1

Descriptive Analysis of Routine Laboratory Testing for Neuraxial Blocks: A Real-world Retrospective Study

Sung ho Moon, Daeseok Oh

Subject: Anesthesiology And Pain Medicine, Medicine And Pharmacology Keywords: neuraxial Blockade; blood tests; comorbidity; preoperative; pain management; glucose

Online: 25 September 2024 (17:54:04 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.2036.v1

The Role of PET/CT in the Management of Differentiated Thyroid Cancer: Current Applications and Future Perspectives

Emmanouil Panagiotidis, Jules Tianyu Zhang-Yin

Subject: Endocrinology And Metabolism, Medicine And Pharmacology Keywords: thyroid cancer; PET/CT

Online: 25 September 2024 (17:02:43 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1975.v1

Biomarkers: The Key To Enhancing Dbs Treatment For Psychiatric Conditions

Guillermo Jose Bazarra Castro, Vicente Casitas, Carlos Martinez-Macho, Alejandra Madero Pohlen, Amelia Alvarez-Sala, Enrique Barbero Pablos, José Fernández Alén, Cristina V. Torres

Subject: Neuroscience And Neurology, Medicine And Pharmacology Keywords: Deep Brain Stimulation (DBS); Psychosurgery; Depression; Obsessive-Compulsive Disorder (OCT); Biomarkers; Diffusion tensor imaging (DTI)

Online: 25 September 2024 (12:46:56 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202409.1988.v1

Management of Postoperative Left-Sided Chylothorax Using Indocyanine Green Fluorescence-Guided VATS

Luigi Lione, Alberto Busetto, Alessandro Bonis, Vincenzo Verzeletti, Eleonora Faccioli, Giovanni Maria Comacchio, Michele Battistel, Alessandro Rebusso, Samuele Nicotra, Federico Rea

Subject: Surgery, Medicine And Pharmacology Keywords: chylothorax; thoracic surgery; indocyanine green fluorescence; lymph nodes

Online: 25 September 2024 (12:43:58 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.2022.v1

Effective Treatment of Basal Cell Carcinoma with a Topical Enzymatic Mixture Enriched in Bromelain: Summary of Proof-of Concept Clinical Studies on the First 22 Tumors

Lior Rosenberg, Yaron Shoham, Brian Berman, Stephen K Tyring, Michael D Tharp, Adam J Singer

Subject: Oncology And Oncogenics, Medicine And Pharmacology Keywords: bromelain; enzymatic debridement; basal cell carcinoma; squamous cell carcinoma; solar actinic keratosis; keratinocyte cancer; 5-flurouracil; imiquimod; photo dynamic therapy

Online: 25 September 2024 (12:25:22 CEST)

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Background/Objectives: Basal cell carcinoma (BCC), the most prevalent form of human cancer, is traditionally treated by surgical and alternative destructive or topical chemical means, each with its advantages, challenges and drawbacks. We describe our experience treating BCCs with a topical concentrate of proteolytic enzymes enriched in bromelain (CPEEB) sourced from pineapple stems. CPEEB has strong proteolytic, antitumor-proapoptotic and inflammation modulation activities, and is approved for debridement of deep burns and starting phase 3 for chronic wounds. Methods: In the first proof of concept (POC) study (published), six BCCs on 3 individuals were treated with 5-6 daily CPEEB 10% topical applications under a Zinc Oxide based occlusive dressing for 9-12 hours each during a period of up to 10 days. These patients were followed for up to 4 years. In an additional 2 POC studies, 16 patients with one BCC each were treated every other day for a total of 7 applications of topical CPEEB 5% under a variety of occlusive dressings. The wounds were followed for up to 2 months before undergoing diagnostic excisional biopsy. Results: In the first study, clinical assessment of the BCCs and 2 excisional biopsies after 6 months suggested that all lesions were eradicated with spontaneous healing within ~2 weeks without clinical or histological recurrence for over 4 years. In the 2 subsequent studies, 16 histologically diagnosed superficial and nodular BCCs were treated using 4 application techniques. Excisional histology after 2 months confirmed BCC eradication in 7 of the patients. In 9 patients, with compromised occlusive dressings, histological eradication was incomplete. Treatment was well tolerated by all patients with the expected local skin reactions that completely healed within 2-3 weeks. Conclusions: Topical CPEEB 10% and 5% resulted complete eradication of the BCC when appropriately applied. CPEEB was well tolerated in all patients and all treated sites’ erosions healed without scars in <3 weeks. Further research is necessary to corroborate the results, refine the application technique and complete the regulatory process.

Preprint ARTICLE | doi:10.20944/preprints202409.1985.v1

Evaluation of an Alternative Screening Method for Gestational Diabetes Diagnosis During the COVID-19 Pandemic (DIABECOVID STUDY): An Observational Cohort Study

Alba Casellas, Cristina Martinez, Judit Amigó, Roser Ferrer, Laia Marti, Carme Merced, M Carmen Medina, Istria Molinero, Marta Calveiro, Anna Maroto, Ester del Barco, Elena Carreras, Maria M. Goya

Subject: Obstetrics And Gynaecology, Medicine And Pharmacology Keywords: Gestational diabetes; COVID-19; O’ Sullivan; OGTT; glucose level; glycated haemoglobin; screening; macrosomia; large for gestational age (LGA); neonatal hypoglycemia

Online: 25 September 2024 (12:18:23 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1999.v1

Ustekinumab Biosimilars

Elena Carmona-Rocha, Lluís Puig

Subject: Dermatology, Medicine And Pharmacology Keywords: psoriasis; biologics; biosimilar; ustekinumab; systemic treatment; IL‐23 inhibitors

Online: 25 September 2024 (12:14:20 CEST)

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Ustekinumab is a fully human IgG1k monoclonal antibody that binds with high affinity and specificity to the p40 subunit of interleukins (IL-) 12 and 23, inhibiting their activity by preventing binding to their receptors. The European extension of the patent (Supplementary Protection Certificate) of ustekinumab expired on July 20, 2024. Biosimilar alternatives to ustekinumab are now an additional option for treating patients. The efficacy data for this drug in moderate-to-severe psoriasis, obtained both from clinical trials and indirect comparisons through meta-analyses, are superior to those of etanercept and adalimumab, and its safety profile is more favorable than that of tumor necrosis factor (TNF) inhibitors. Several ustekinumab biosimilars have already been approved by regulatory agencies: between October 2023 and July 2024, Wezlana® (Amgen ABP 654), Uzpruvo® (Alvotech AVT04) and Pyzchiva® (Samsung/Bioepis SB17) have been approved by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). SteQeyma® (Celltrion Healthcare CT-P43) has been approved by the EMA in August 2024. Several other potential biosimilar candidates are under development, including FYB202 (Formycon), BAT2206 (Bio-Thera), DMB-3115 (Dong-A ST), QX001S (Qyuns Therapeutic), BFI-751 (BioFactura), NeuLara (Neuclone), ONS3040 (Oncobiologics), and BOW090 (Epirus Biopharmaceuticals). In most cases, these monoclonal antibodies are expressed in cell lines (e.g. Chinese Hamster Ovary, CHO) different from those used for the originator (Sp2/0 spleen cell murine myeloma); of note, the cell line of origin is not a requirement for biosimilarity in the totality-of-evidence comparison exercise and may facilitate the production and reduce the immunogenicity of biosimilars originated in CHO cultures. This narrative review will summarize the available data on characteristics of the full comparability exercises and comparative clinical trials of these drugs.

Preprint REVIEW | doi:10.20944/preprints202409.2011.v1

Crossing Age Boundaries: The Unifying Potential of Presepsin in Sepsis Diagnosis Across Diverse Age Groups

Edmilson Leal Bastos de Moura, Rinaldo Wellerson Pereira

Subject: Clinical Medicine, Medicine And Pharmacology Keywords: sepsis; biomarkers; presepsin; elderly; neonates; adults

Online: 25 September 2024 (12:12:13 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.2002.v1

Limited Local Clinical Trials for the New Cancer Treatment Technology Karanahan for Patients with Advanced Breast Cancer

Veronika A Markina, Anastasia S Proskurina, Vera S Ruzanova, Genrikh S Ritter, Evgeniya V Dolgova, Svetlana S Kirikovich, Evgeniy V Levites, Sofya G Oshihmina, Yaroslav R Efremov, Eugene I Vereschagin, Olga Y Leplina, Alexandr A Ostanin, Elena R Chernykh, Nikolay A Kolchanov, Sergey V Sidorov, Sergey S Bogachev

Subject: Oncology And Oncogenics, Medicine And Pharmacology Keywords: breast cancer; cyclophosphamide; double-stranded DNA; palliative patients

Online: 25 September 2024 (12:01:00 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1989.v1

The Relationship between Understanding Diversity and Brain Health, Focusing on the Triple Network

Taiko Otsuka, Keisuke Kokubun, Maya Okamoto, Yoshinori Yamakawa

Subject: Psychiatry And Mental Health, Medicine And Pharmacology Keywords: diversity; gender; gray matter volume; LGBTQ; race; triple network

Online: 25 September 2024 (11:50:58 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1907.v1

Histopathological Insights and Therapeutic Prospects of MCC950 in Diabetic Cardiac Autonomic Neuropathy in a Type 1 Diabetes Wistar Rat Model

Shamala Devi Subramaniam, Juita Chupri, Zamzarina Ahmad Bajari, Kah Hui Wong, Mohd Amir Kamaruzzaman, Razif Abas

Subject: Cardiac And Cardiovascular Systems, Medicine And Pharmacology Keywords: Diabetic Cardiac Autonomic Neuropathy (DCAN); Type 1 Diabetes Mellitus (T1DM); MCC950; NLRP3 Inflammasome; Histopathology

Online: 25 September 2024 (11:00:51 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1939.v1

Enhanced Ocular Drug Delivery of Dexamethasone Using Chitosan-Coated Soluplus® Based Mixed Micellar System

Samer Adwan, Faisal Al-Akayleh, Madeha Qasmieh, Teiba Obeidi

Subject: Pharmacy, Medicine And Pharmacology Keywords: Soluplus®; Pluronic F-127; Dexamethasone; Mixed micelle; Chitosan coat

Online: 25 September 2024 (10:25:00 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1960.v1

Antibody-Drug Conjugates and Their Potential in the Treatment of Patients with Biliary Tract Cancer

Shaun Alexander, Umair Aleem, Timothy Jacobs, Melissa Frizziero, Victoria Foy, Richard A Hubner, Mairéad G McNamara

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Antibody drug-conjugate; biliary tract cancer; anti-HER2; payload; targeted therapy

Online: 25 September 2024 (09:00:59 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1965.v1

Resveratrol and Exercise Produce a Recovery Ankle and Metatarsus Joint Movements After a Penetrating Lesion in the Hippocampus in Male Rats

Irene Guadalupe Aguilar-Garcia, Jonatan Alpirez, Rolando Castañeda-Arellano, Judith Marcela Dueñas-Jiménez, Maria del Carmen Toro-Castillo, Lilia Carolina León-Moreno, Laura Paulina Osuna-Carrasco, Sergio Horacio Dueñas-Jiménez

Subject: Neuroscience And Neurology, Medicine And Pharmacology Keywords: Locomotion; Kinematics; Resveratrol; exercise

Online: 25 September 2024 (09:00:52 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202409.1967.v1

Cervical Mesonephric Adenocarcinoma Treated with Neoadjuvant Chemotherapy. A Case Report and a Literature Review

Hiroaki Ishida, Megumi Manrai, Hiroki Egashira, Mizuki Nonaka, Nobuyuki Hiruta, Reiko Watanabe, Akiko Takashima

Subject: Medicine And Pharmacology, Obstetrics And Gynaecology Keywords: Cervical mesonephric adenocarcinoma; Neoadjuvant chemotherapy; Adjuvant chemotherapy

Online: 25 September 2024 (08:52:06 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1943.v1

Blood-Brain Barrier Integrity Disruption is Associated to both Chronic Vascular Risk Factors and White Matter Hyperintensities

James Xiao Yuan Chen, Ashwati Vipin, Gurveen Kaur Sandhu, Yi Jin Leow, Fatin Zahra Zailan, Pricilia Tanoto, Ee Soo Lee, Khang Leng Lee, Christine Cheung, Negaenderan Kandiah

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: cerebral small vessel disease; blood-brain barrier; cardiovascular risk factors; white matter hyperintensity; transendothelial electrical resistance assay

Online: 25 September 2024 (08:26:47 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1971.v1

Nanotechnological Advances in Burn Wound Care: Chitosan-Based Nanogel Incorporating Silver Sulfadiazine-loaded Nanosuspension for Partial Thickness Burns

Harshita Barkat, Md. Abul Barkat, Raisuddin Ali, Hazrina Ab Hadi

Subject: Medicine And Pharmacology, Pharmacy Keywords: nanosuspension; topical delivery; burn wound infection; nanogel; chitosan ;

Online: 25 September 2024 (05:24:59 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1934.v1

Fluid Overload in Children Following Hematopoietic Cell Transplant: A Cause for Concern?

Lama Elbahlawan, Amr Qudeimat, Ray Morrison, Alexandra Schaller

Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: Fluid overload; fluid accumulation; hematopoietic cell transplant; pediatrics; critically ill; outcome; acute kidney injury

Online: 25 September 2024 (04:24:34 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1945.v1

Perirenal Fat CT Radiomics-Based Survival Model for Upper Tract Urothelial Carcinoma: Integrating Texture Features with Clinical Predictors

Abdulrahman Nasser M Al Mopti, Abdulsalam Mohammed Alqahtani, Ali H D Alshehri, Chunhui Li, Ghulam Nabi

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Upper tract urothelial carcinoma; Perirenal fat radiomics; Prognostic modelling; CT imaging; Machine learning; texture analysis; survival; prognosis

Online: 25 September 2024 (04:21:39 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1929.v1

Vitamin D’s Essential Role from Natural Sources in Preventing Rhinosinusitis, Nasopharyngitis, and Otitis Media: Ensuring Optimal Care in Patients with Behavioral Disorders

Felicia Manole, Alexia Manole, Timea Claudia Ghitea

Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: behavior disorders; nasopharyngitis; otitis media; rhinosinusitis; vitamin D

Online: 25 September 2024 (04:18:04 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1931.v1

Extracorporeal Photopheresis of Patients with Crohn’s Disease Using 5-Aminolevulinic Acid – a First-in-Human Phase I/II Study

Kristian Espeland, Eidi Christensen, Astrid Aandahl, Andreas Ulvær, Trond Warloe, Andrius Kleinauskas, Sagar Darvekar, Petras Juzenas, Vlada Vasovic, Qian Peng, Jørgen Jahnsen

Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: Crohns disease, extracorporeal photopheresis, ECP, 8-MOP, UV-A, blue light.

Online: 24 September 2024 (14:21:21 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1900.v1

Prognostic Value of Separate Extramural Vascular Invasion Reporting in Operative Samples of Rectal Cancer: Single-Institutional Experience

Mladen Đurić, Bojana Kožik, Tijana Vasiljević, Aleksandar Đermanović, Nevena Stanulović, Marina Đurić

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Rectal cancer (RC); Extramural venous invasion (EMVI); Predictive Medicine

Online: 24 September 2024 (14:04:05 CEST)

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Background/Objectives: Vascular invasion, especially extramural vascular invasion (EMVI) has emerged as prognostic parameter for rectal cancer (RC) in recent years. Prediction of reccurence and metastases development poses a significant challenge for oncologists, needing markers for prediction of adverse outcome. The aim of this study was to examine the prognostic significance of pathohistologically detected EMVI in untreated rectal cancer and its implications in separate reporting. Methods: We examined 100 untreated RC patients who underwent curative resection from January 2016 to June 2018 with follow up of 5 years. Patients were divided in equal EMVI- and EMVI+ groups based on histological re-examination of H&E stained postoperative surgical samples. Results: The presence of EMVI within the selected cohort was significantly associated with female gender, T3/T4 and N1/N2 post-operative stages, positive lymph nodes, lymph node ratio LNR2 and LNR3 groups, abundant tumor-infiltrating lymphocytes, positive lympho-vascular invasion (LVI), perineural (PNI), and circumferential resection margin (CRM) (p<0.05 in all tests). Within EMVI+ patients, local recurrences and/or metastases, and death outcomes were more frequent events (p=0.029 and p=0.035, respectively), while survival analyses revealed that EMVI+ patients had significantly shorter overall survival (OS, p=0.040) and disease-free survival (DFS, p=0.028). Concerning LVI, differences in OS between LVI+ and LVI- patients were not statistically significant (p=0.068), while LVI+ patients had significantly shorter DFS (p=0.024). Moreover, univariate COX regression analysis demonstrated the negative impact of EMVI on OS (HR: 2.053, 95% CI: 1.015-4.152; p=0.045) and DFS (HR: 2.106, 95% CI: 1.066-4.870; p=0.038), which was not the case for LVI+ RC patients. Conclusions: Obtained results strongly suggest significance of separate reporting of EMVI from lympho-vascular invasion, as it is potentially a surogate marker for adverse prognosis and outcome.

Preprint REVIEW | doi:10.20944/preprints202409.1922.v1

Impact of Daratumumab in Transplant Eligible/Ineligible Patients with Newly Diagnosed Multiple Myeloma: An Updated Meta-Analysis of Phase- III Trials

Bolivia Crocete Aloysia Fernandes, Vedant Shah, Muhammad Ashar Ali, Rahul Mehta, Prakash Chano Mal, Jannat Sardar Sheikh, Sulochana Gnanasekaran, Makarand Madine, Arya Alla, Sucharitha Pandeti, Jamarc Simon, Vinod Nookala

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: daratumumab; multiple myeloma; meta-analysis

Online: 24 September 2024 (14:01:46 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1906.v1

Links Between Attention-Deficit/Hyperactivity Disorder Symptoms, Peer Relationships and Mental Health Outcomes in Western Australian Youth

Carolyn Maxwell, Stephen Houghton, Elaine Chapman

Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: Peer relationships; attention-deficit/hyperactivity; mental health; adolescents

Online: 24 September 2024 (14:01:04 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1855.v1

Antimicrobial Susceptibility of Uropathogenic Escherichia coli with Analysis of Impact of Socio-Economic Factors in Low, Medium and High-Income Countries

Meher Rizvi, Maria Khan, Amina AL Jardani, Ujjala Ghoshal, Zaaima AL Jabri, Mohammad Ahanjan, Azza AL Mamari, Nawal AL Shizawi, Hiba Sami, Abdullah Balkhair, Adila Shaukat, Alwarith Nasser Salem Alkharusi, Abdulrahman Almahrouqi, Afreenish Hassan, Ajay Kumar, Amal Malehi, Amina Gul, Ashima Singh, Asma Said Hamed AL Shidhani, Areena Hoda Siddiqui, Aruna Poojary, Azza AL Rashdi, Bradley Langford, Dmytro Stepanskyi, Abbas Dolatabadi, Aisha Al Mufraji AL Mufraji, Elham Said Ahmed AL Risi, Garima Kapoor, Isabella Princess, Hatim Ali Eltahir, Hilal Al Sidairi, Kaitlyn Dougherty, Katia Iskandar, Ken Masters, Ibrahim Khalaf Hamdan AL Busaidi, Laila AL Yazidi, Mahfuza Nasrin, Mahmood Salim AL Subhi, Mallika Sengupta Mallika Sengupta, Manisha Khandait, Nada Khalfan AL Tamtami, Nada Khafan Alsiyabi, Nawal AL Kindi, Nazla Musthafa Luthfee, Neha Shreshtha, Nihal Mohamed Amur AL Riyami, Noora Hilal Ali AL Busaidi, Nupur Goel, Oksana Ishchenko, Omnia Mohamed Elnabawy Ahmed Taher, Pragnya Paramita Jena, Rajni Ekadashi, Razan Zadjali, Reba Kanungo, Sara Abolghasemi, Salima Al-maqbali, Sanjay Jaju, Sayantan Banerjee, Shadma Yaqoob, Shahnaz Sali, Shafqat Husnain Khan, Shalini Malhotra, Stephen Hughes, Sundas Shaukat, Syed Mohammed Atif, Vrushali Vishwas Patwardhan, Victorien Dougnon, Wahid Khan, Walid Wali, Zakariya AL Muharrmi, Zeeshana Basit, Jasashree Choudhury, Rachita Pravalina, Sanjeev Singh, Sarman Singh, Neelam Taneja, Raman Sardana, Pawan Kapoor, Rajeev Soman, Rashid Al Abri

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: community acquired UTI; Escherichia coli; antimicrobial susceptibility; Indian subcontinent; MENA; GDP; temperature

Online: 24 September 2024 (12:32:05 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1873.v1

Correlation Between IgA Levels in Henoch–Schönlein Purpura and a Medical History of Infectious Disease in the Pediatric Population: A Five-Year Retrospective Analysis

Sînziana Oprițescu, Gabriela Viorela Nițescu, Mihaela Golumbeanu, Dora Boghițoiu, Elena Iuliana Ioniță, Diana-Andreea Ușurelu, Cristian Lucaci, Adriana Negoiță, Elena Moroșan

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Henoch–Schönlein purpura; IgA vasculitis; allergic vasculitis; infectious diseases

Online: 24 September 2024 (11:57:35 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1771.v1

Sputum Induction in Pediatric Lung Disease: Are We There Yet?

Tuba Kockar Kizilirmak, Emanuela M Bruscia, Clemente J Britto, Marie E Egan

Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: Induced sputum; airway inflammation; respiratory; children

Online: 24 September 2024 (11:26:12 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1862.v1

Evaluation of Chronic Pain Development in Patients Undergoing Shoulder Arthroscopy

Teoman Etikcan, Keziban Sanem Cakar Turhan, Suheyla Karadag Erkoc, Hanzade Aybuke Unal

Subject: Medicine And Pharmacology, Anesthesiology And Pain Medicine Keywords: chronic pain; postoperative pain; arthroscopy

Online: 24 September 2024 (11:04:42 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1838.v1

Cutting Through History: The Evolution of Glioblastoma Surgery

Abdullah Ishaque, Sunit Das

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: glioblastoma; surgery; history

Online: 24 September 2024 (11:02:31 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1896.v1

MPV17 Prevented Myocardial Ferroptosis and Ischemic Cardiac Injury through Maintaining SLC25A10 Mediated Mitochondrial Glutathione Import

Tao Xu, Guilan Chen

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: ischemia/reperfusion injury; iron overload; myocardial ferroptosis; MPV17; mtGSH

Online: 24 September 2024 (10:49:04 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1883.v1

Paper‐and‐Pencil vs. Electronic Patient Records: Analyzing Time Efficiency, Personnel Requirements, and Usability Impacts on Healthcare Administration

Matthias Fabian Berger, Johanna Petritsch, Andrzej Hecker, Sabrina Pustak, Birgit Michelitsch, Chiara Banfi, Lars-Peter Kamolz, David B. Lumenta

Subject: Medicine And Pharmacology, Clinical Medicine Keywords: digital medicine; electronic patient record; electronic health record; clinical decision support; data science

Online: 24 September 2024 (10:06:56 CEST)

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Objective The healthcare industry has witnessed a paradigm shift with the adoption of Electronic Patient Records (EPRs), transitioning from traditional Paper and Pencil (P&P) methods to sophisticated, technology-driven documentation systems. However, the integration of EPRs into clinical settings has introduced new challenges. This study investigates workflow consequences of switching from P&P to EPR systems. Methods In this study, two independent observers audited surgical ward rounds to assess the effects of transitioning from P&P to EPR. These audits captured number of medical personnel and five key aspects before and after EPR implementation. Additionally, the EPR system's usability was gathered through the System Usability Scale (SUS) and the Post Study System Usability Questionnaire (PSSUQ). Results A total of 192 observations using P&P and 160 with the EPR system were analyzed. Results indicated that physicians spent a lower proportion of time in patient rooms using the P&P modality (median = 0.14, IQR = [0.06, 0.24]) compared to the EPR system (median = 0.19, IQR = [0.12, 0.29]). Conversely, nurses spent more time with the P&P modality (median = 0.13, IQR = [0.08, 0.18]) than with the EPR system (median = 0.10, IQR = [0.06, 0.13]). The typical team in the P&P modality comprised two physicians and four nurses, while teams in the EPR system generally included two or three physicians and three nurses. Usability assessments yielded scores rated as "Not Acceptable." Conclusion The EPR is already known to contribute to an increased administrative burden. Our findings generally align with this view in the physician sample, whereas nurses did not encounter difficulties switching systems. However, usability scores indicated that the EPR system falls short of meeting user acceptance expectations. Given the continuous increase in administrative workload, our results suggest that ururcing administrative tasks could enhance the efficiency of medical duties performed at patient's bedside.

Preprint ARTICLE | doi:10.20944/preprints202409.1886.v1

Interplay of Physical Exercise with Leptin and Ghrelin Alterations After Roux-en-Y-Gastric Bypass in Patients with Sarcopenic Obesity

Cláudia Mendes, Manuel Carvalho, Jorge Bravo, Sandra Martins, Armando Raimundo

Subject: Medicine And Pharmacology, Surgery Keywords: sarcopenia; sarcopenic obesity; bariatric surgery; leptin; ghrelin; exercise

Online: 24 September 2024 (09:45:40 CEST)

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Introduction: Leptin and ghrelin are two hormones that play a role in weight homeostasis. Leptin, which is produced primarily by adipocytes and is dependent on body fat mass, suppresses appetite and increases energy expenditure. Conversely, ghrelin is the “hunger hormone”, it stimulates appetite and promotes fat storage. Bariatric surgery significantly alters the levels and activity of these hormones, contributing to weight loss and metabolic improvements. Clarifying the interplay between bariatric surgery, weight loss, physical exercise, leptin, and ghrelin is essential for developing comprehensive strategies for optimizing long-term outcomes for candidates for bariatric surgery, especially sarcopenic patients. Methods: This was a randomized controlled study with two groups (n=22). The patients in both groups have obesity and sarcopenia. A Roux-en-Y-gastric bypass (RYGB) procedure was performed in all patients. The intervention group participated in a structured exercise program three times per week beginning one month after surgery and lasting 16 weeks. Patient assessment was performed before surgery (baseline) and after completion of the exercise program. The control group received the usual standard of care and was assessed similarly. Results: After surgery, weight, BMI and lean mass decreased significantly in both groups from baseline to the second assessment. Leptin was not significantly different from baseline to the second assessment in the physical exercise group but was significantly lower in the control group (p=0.05). Ghrelin increased over time in both groups, but the differences were not significant. When we associated leptin (the dependent variable) with weight (the independent variable), we found that lower weight was associated with lower leptin levels. A similar relationship was also observed between leptin and sarcopenia parameters (muscle strength and mass), as well as with bone health parameters (bone mineral density and t-score). Higher ghrelin levels were significantly associated with higher t-scores and z-score (p

Preprint REVIEW | doi:10.20944/preprints202409.1823.v1

Glucocorticoid Receptor Alpha: Origins and Functions of the Master Regulator of Homeostatic Corrections in Health and Critical Illness

Gianfranco Umberto Meduri

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: acute phase response; acute respiratory distress syndrome; allostasis; chromatin; chronic; co-regulation; critical illness; dysregulated systemic inflammation; endothelium; evolution; general adaptation syndrome; glucocorticoid; glucocorticoid receptor; homeostasis; homeostatic corrections; long-term; micronutrients; mitochondria; nuclear factor kappa B; reactive oxygen species; regulation; resolution; sepsis; stress response; systemic inflammation; treatment; vertebrates

Online: 24 September 2024 (09:22:30 CEST)

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The glucocorticoid receptor alpha (GRα), a pivotal component of the ancient glucocorticoid (GC) signaling system that emerged nearly 450 million years ago, has been instrumental in directing vertebrate evolution and is essential for survival, regulating fertility and fetal development, the function of every organ and circulating cells, metabolism, immune responses, and adaptation to stress. While its anti-inflammatory properties have been recognized since the mid-20th century, GRα’s broader role as the master regulator of homeostatic corrections, particularly in health and critical illness, has only recently been fully appreciated.GRα orchestrates three key phases of homeostatic correction: the Priming Phase, where it rapidly activates early immune responses, mobilizes energy reserves, and prepares the body to mount an immediate defense against various physiological stressors, including infection and injury. During this phase, GRα enhances glucose metabolism, supports mitochondrial function, and facilitates the release of key immune cells to the site of damage, ensuring the body is equipped to handle the initial assault. The Modulatory Phase follows, in which GRα fine-tunes the inflammatory response to prevent excessive tissue damage. By balancing pro- and anti-inflammatory signals, GRα helps contain the immune response, preventing the harmful effects of prolonged inflammation while maintaining immune surveillance. This phase also involves the regulation of oxidative stress, vascular tone, and the preservation of cellular integrity to protect vital organs from injury. Finally, in the Restorative Phase, GRα plays a critical role in resolving inflammation and initiating tissue repair. During this phase, GRα supports cellular regeneration, promotes the clearance of apoptotic cells and debris, and restores anatomical and physiological balance. It aids in rebuilding tissue architecture and returning the neuroendocrine-immune system to its baseline state, ensuring long-term recovery and stability.Throughout these phases, GRα manages complex interactions, including recently discovered co-regulation with pro-inflammatory transcription factors, while also regulating mitochondrial function to ensure bioenergetic and metabolic stability during stress. In critically ill patients, depletion of bioenergetic and micronutrient reserves severely impairs GRα’s capacity to regulate immune responses, heightening the risk of morbidity and mortality.This review, in light of this new understanding, underscores the need to re-evaluate current glucocorticoid (GC) treatment strategies, emphasizing the incorporation of micronutrient support to optimize GRα function across all phases of homeostatic correction. This integrated therapeutic approach has the potential to enhance both immediate immune responses and long-term recovery in critically ill patients, offering a more comprehensive strategy for managing the complex pathobiology of critical illness. Furthermore, this integrative approach could decrease glucocorticoid dose and duration requirements and potential side effects.

Preprint ARTICLE | doi:10.20944/preprints202409.1824.v1

Longitudinal Fecal Microbiota Profiles in a Cohort of Non-Hospitalized Adolescents and Young Adults with COVID-19: Associations with SARS-CoV-2 Status and Long-Term Fatigue

Christine Olbjørn, Milada Hagen, Aina Fossum Moen, Lise Beier Havdal, Silke Lauren Sommen, Lise Lund Berven, Espen Thiis-Evensen, Tonje Stiansen-Sonerud, Joel Selvakumar, Vegard Bruun Bratholm Wyller

Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: SARS-CoV-2; COVID-19; fatigue; post-COVID-19 condition; post-infective fatigue syndrome; microbiota; Faecalibacterium prausnitzii; Sutterella wadsworthensis

Online: 24 September 2024 (09:20:10 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1826.v1

Coley`s Toxin to first Approved Therapeutic Vaccine - a Brief Historical Account in the Progression of Immunobiology Based Cancer Treatment

K. Devaraja, Manisha Singh, Krishna Sharan, Sadhna Aggarwal

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Coley`s toxin; T-lymphocytes; Dendritic cells; Immunosurveillance; Immunoediting; Tumor microenvironment; Head and Neck neoplasm; Immunotherapy; Therapeutic vaccines; Checkpoint inhibitors; Immunobiology

Online: 24 September 2024 (09:19:06 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1776.v1

Autism Spectrum Disorder Pathogenesis – a Cross-Sectional Literature Review with Emphasis to Molecular Aspect

Agata Horecka-Lewitowicz, Wojciech Lewitowicz, Monika Wawszczak-Kasza, Hyebin Lim, Lewitowicz Piotr

Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: keyword ASD; Asperger syndrome; autism; molecular sequencing

Online: 24 September 2024 (09:02:45 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1815.v1

Bridging the Gap: Improving Acute Ischemic Stroke Outcomes with Intravenous Thrombolysis Prior to Mechanical Thrombectomy

Jessica Seetge, Balázs Cséke, Zsófia Nozomi Karádi, Edit Bosnyák, László Szapáry

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: acute ischemic stroke; intravenous thrombolysis; mechanical thrombectomy; bridging

Online: 24 September 2024 (07:34:14 CEST)

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Background/Objectives: Current guidelines recommend intravenous thrombolysis (IVT) followed by mechanical thrombectomy (MT) for patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). This combined approach, known as bridging therapy (BT), is believed to increase the likelihood of a favorable functional outcome when administered within 4.5 hours of symptom onset. However, the benefits of BT over direct mechanical thrombectomy (d-MT) remain debated. This study aimed to compare the outcomes of AIS-LVO patients undergoing MT within 6 hours of symptom onset, with and without prior IVT. Methods: Within the prospective TINL STROKE-registry, AIS-LVO patients admitted to the Department of Neurology, University of Pécs, between February 2023 and June 2024 were investigated. The primary endpoint was the proportion of patients reaching functional independence at 90 days, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary endpoints included clinical improvement at 72 hours (National Institute of Health Stroke Scale [NIHSS] score of ≤1 or a change from baseline [ΔNIHSS] of ≥4) and successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] score ≥2). Safety outcomes were evaluated based on thrombus migration and intracranial hemorrhage (ICH). Results were compared using linear and logistic regression analyses adjusted for baseline variables. Results: Of 82 patients, 51 (62.2%) received BT, while 31 (37.8%) underwent d-MT. The BT group showed a significantly higher rate of functional independence (45.7% vs. 17.2%, p=0.014) and a lower 90-day mortality rate (13.7% vs. 35.5%, p=0.029). Multivariate analysis revealed that IVT was independently associated with favorable functional outcome (p=0.011) and reduced mortality (p=0.021). No significant differences were observed in terms of clinical improvement at 72 hours, successful recanalization, thrombus migration, or hemorrhagic transformation between the groups. Conclusions: This study supports current guidelines recommending BT for thrombectomy-eligible AIS-LVO patients, offering new insights into the ongoing clinical debate.

Preprint BRIEF REPORT | doi:10.20944/preprints202409.1863.v1

Safety and Tolerability of a Shorter Agalsidase Beta Infusion Time in Patients with Classic or Later-onset Fabry Disease

Dominique P Germain, Alice Porto Vasconcelos, Liên Tran Thi Phuong, Najya Bedreddine, Mihaela Turcan, Wenting Trang, Lynda Barache

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: Fabry disease; agalsidase beta; quality of life; reduced infusion time; safety; tolerability

Online: 24 September 2024 (05:53:29 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1798.v1

Exosome-Derived microRNAs in Hypertrophic Cardiomyopathy

Brian Xiangzhi Wang

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: miRNA; exosome; hypertrophy; calcium cycling; remodeling

Online: 24 September 2024 (05:12:34 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1789.v1

Real-World Effectiveness of Inactivated COVID-19 Vaccines in Zimbabwe during the Omicron Variant Dominance: A Test-Negative Case-Control Study

Azure Tariro Makadzange, Patricia Gundidza, Kimberley Konono, Margaret Gurumani, Chiratidzo Ndhlovu

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; Vaccine Effectiveness; Inactivated Vaccines; SARS-CoV-2; Omicron Variant; Test-Negative Case-Control Study; Zimbabwe; Sinopharm; Sinovac

Online: 24 September 2024 (05:03:51 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1765.v1

External Scaffold for Strengthening the Pulmonary Autograft in the Ross Procedure

Francesco Nappi, Aubin Nassif, Thibaut Schoell

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Pulmonary Autograft; Biomechanics; Remodeling; Scaffold

Online: 24 September 2024 (04:57:37 CEST)

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Preprint DATA DESCRIPTOR | doi:10.20944/preprints202409.1714.v1

Genomic Typing, Antimicrobial Resistance Gene and Virulence Factor Dataset for the Important Pathogenic Bacteria Klebsiella pneumoniae

Andrey Shelenkov, Anna Slavokhotova, Yulia Mikhailova, Vasiliy Akimkin

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Klebsiella pneumoniae; healthcare-associated infections; genomic epidemiology; whole genome sequencing; cgMLST; global clones; antibiotic resistance; virulence factors

Online: 24 September 2024 (04:05:48 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1701.v1

Blood-Based Biomarkers in Alzheimer's Disease: Advancing Non-Invasive Diagnostics and Prognostics

Mrinmay Dhauria, Ritwick Mondal, Shramana Deb, Gourav Shome, Dipanjan Chowdhury, Shramana Sarkar, Julián Benito-León

Subject: Neuroscience And Neurology, Medicine And Pharmacology Keywords: Alzheimer's disease (AD); blood-based biomarkers; amyloid-beta (Aβ); phosphorylated tau (p-Tau); neurofilament light polypeptide (NfL); non-invasive diagnostics; neurodegeneration; proteinopathy; neuroinflammation; vascular pathology; early detection; prognostics; advanced neuroimaging; dementia

Online: 24 September 2024 (03:50:12 CEST)

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Alzheimer's disease (AD) is the most prevalent form of dementia. With the global aging population, the incidence of AD and related dementias is projected to rise dramatically, posing significant public health challenges. Traditionally, the diagnosis of AD has relied on the detection of amyloid-beta (Aβ) plaques and neurofibrillary tangles of hyperphosphorylated tau in the brain, assessed through invasive cerebrospinal fluid (CSF) analysis and costly positron emission tomography scans. However, these methods are not feasible for widespread screening or use in low-resource settings. Recent advances in blood-based biomarkers offer a promising alternative for the early detection and monitoring of AD. These biomarkers provide a minimally invasive, cost-effective means of tracking the pathological progression of AD before the onset of clinical symptoms, potentially enabling earlier and more accurate diagnosis. Blood-based biomarkers, including those related to Aβ, phosphorylated tau, and neurofilament light polypeptide, have demonstrated significant potential in reflecting the underlying neuropathology of AD and correlating with traditional CSF and imaging biomarkers. This review synthesizes the latest research on blood-based biomarkers in AD, highlighting their role in the disease's etiopathogenesis, diagnostic accuracy, and prognostic value. We discuss the emerging evidence on proteinopathies, neuroinflammation, vascular pathology, and bioenergetic profiles, emphasizing the clinical applicability of these biomarkers. Furthermore, we explore the integration of blood-based biomarkers with advanced neuroimaging techniques and their potential to revolutionize the diagnostic landscape of AD, particularly in resource-limited settings. We have integrated protein-protein interaction (PPI) and miRNA network analyses to enhance the analysis. By incorporating these, we can explore the interactions and relationships between different proteomic, genomic, and epigenomic biomarkers, potentially unveiling new insights into the underlying biological mechanisms of AD. The continued development and validation of these biomarkers could lead to more accessible and equitable AD diagnostics, ultimately improving patient outcomes.

Preprint ARTICLE | doi:10.20944/preprints202409.1671.v1

Combination Therapy for Multi-Drug-Resistant Mycoplasma genitalium

Chris Kenyon

Subject: Medicine And Pharmacology, Internal Medicine Keywords: M. genitalium; minocycline; metronidazole; methenamine; pristinamycin; AMR

Online: 24 September 2024 (03:49:18 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1822.v1

The Efficacy of Topically Applied Curcumin 1% as Alternative or Complementary to Triamcinolone Acetonate in Treatment of Oral Lichen Planus (Randomize Control Trial)

Shimaa Kotb, Barra Alaa El Din, Mohamed Edrees

Subject: Medicine And Pharmacology, Dentistry And Oral Surgery Keywords: Immune mediate inflammatory diseases; Oral lichen planus; Interlukin 6; topical corticosteroids; Curcumin

Online: 24 September 2024 (00:17:02 CEST)

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Aim of study: to evaluate the therapeutic impact of topically applied curcumin as Alternative or Complementary to Triamcinolone Acetonate in Treatment of Oral Lichen Planus. Background: Oral lichen planus (OLP) is a chronic inflammatory disorder affecting the mucous membranes, believed to be an immune-mediated condition. Its persisting nature can lead to extended discomfort for those affected. The primary symptoms are pain and a burning sensation, with a potential risk of malignancy if not properly managed, necessitating lifelong clinical monitoring. Presently, OLP is considered a significant challenge due to the absence of a definitive cure. Patients & patients: Thirty patients with oral lichen planus were divided into three groups, 10 patients each: Group A: ten patients with OLP were received topical triamcinolone acetonide. Group B: ten patients with OLP were received topical curcumin. Group C: ten patients with oral lichen planus were received topical triamcinolone acetonide combiend with topical curcumin. For six weeks. Each patient was examined at baseline, 1 and 3months of therapy. Pain was scored using the visual analogue scale. Salivary level of interleukin 6 were estimated at baseline, 1 and 3months evaluation periods. Results: Significant decrease in pain score was observed in all groups and there was a statistically significant difference between them at all treatment periods in favor to group C . 2 Additionally, all groups showed a decrease in the size of lesions which was greater in group A,C compared to the B group. A significant reduction of the mean interlukin6 continued down to 3 months in all groups with statistically insignificant difference between them at three months, while statistically significant difference in favor to group C at 1month was observed. Conclusion: The results proved the benefit of curcumin as a promising medication when used in combination with conventional therapy in treatment of OLP patients. However, further longterm studies with large sample size are needed.

Preprint REVIEW | doi:10.20944/preprints202409.1810.v1

Indoleamine 2,3-Dioxygenase 2 (IDO2): The Protein That Lived Twice

Chiara Suvieri, Maria Laura Belladonna, Claudia Volpi

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: indoleamine 2,3-dioxygenase 2 (IDO2); cancer; signaling function; tryptophan metabolism; indoleamine 2,3-dioxygenase 1 (IDO1); apo-enzyme

Online: 23 September 2024 (15:31:46 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1807.v1

Metabolic Reprogramming Induced by Aging Modifies the Tumor Microenvironment

Chen Huang, Xingyu Chen, Zihan Wang, Bo Zhu, Min Deng, Jiayue Qiu, Yunwen Feng, Ning Ding

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Metabolic reprogramming; aging; metabolic plasticity; tumor immune microenvironment; pan-cancer; glioma; scRNA sequencing analysis

Online: 23 September 2024 (15:26:34 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1806.v1

Antiaging Properties of Kalanchoe blossfeldiana Ethanol Extract – Ex Vivo and In Vitro Studies

Justyna Stefanowicz-Hajduk, Anna Nowak, Anna Hering, Łukasz Kucharski, Piotr Graczyk, Mariusz Kowalczyk, Tadeusz Sulikowski, Anna Muzykiewicz Szymańska

Subject: Medicine And Pharmacology, Dermatology Keywords: Kalanchoe blossfeldiana; hydrogels; antioxidant activity; skin penetration; elastase; hyaluronidase

Online: 23 September 2024 (15:15:37 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1788.v1

Outbreak of Esophagitis and Ingluvitis Caused by Salmonella Typhimurium in Passeriform Birds of the Genus Sporophila Seized from Wildlife Trafficking

Karoline L. Soares, Ewerton S. Lima¹, Millena de O. Firmino, Eduardo M. Ramos-Sanchez, Lilian Eloy, Raquel Silva, Mônica Sousa, Isabelle Sousa, Weslley Silva, Artur Fernandes, Ricardo B. Lucena

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: avian pathology; histopatology; microbiology; MALDI-TOF; molecular serotyping; One Health; salmonellosis

Online: 23 September 2024 (15:11:38 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202409.1791.v1

Curly Hair Follicle is Sculpted by a Contracted Arrector Pili Muscle. A Hypothesis with Treatment Implications

Nedaa Al Jasim

Subject: Medicine And Pharmacology, Dermatology Keywords: hair follicle; arrector pili muscle; hair types; classification; curly hair; coily; curved follicle; root cause; mechanical force; relaxation from within; ingestible hair relaxing; oral; piloerection; goosebumps

Online: 23 September 2024 (14:26:24 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1726.v1

Diagnostic Accuracy of Glutamate Dehydrogenase Enzyme (GDH) for Clostridium difficile Infection: A Meta-Analysis

Dev Desai, Manav Patel, Heer Shah, Pankil Thaker

Subject: Medicine And Pharmacology, Other Keywords: Glutamate Dehyrogenase; Clostridium difficile; Diagnostic test accuracy; Reference standard

Online: 23 September 2024 (13:15:41 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1751.v1

From Mechanical Machining Technology: A New Solution that Integrates Blades to the Implant to Control the Stress to the Peri-Implant Cortical Bone

Mauro Ferri, Marco Guzzo, Hiroyuki Omori, Yuma Hazama, Nicodemo Vittorio Masotta, Botticelli Daniele

Subject: Medicine And Pharmacology, Dentistry And Oral Surgery Keywords: bone loss; cortical decompression; peri-implant resorption; osseointegration with autologous bone; alveolar precision

Online: 23 September 2024 (12:57:03 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1778.v1

Evaluating Short-Term Intensive Insulin Intervention in Newly Diagnosed Type 2 Diabetes: A Meta-Analysis Perspective

Mounika Nagarani Tunuguntla, Rukesh Yadav, Prashant Obed Reddy, Pranathi Chanti, Ummadi Venkata Nitish Reddy, Haitham Alhussain, Akshita Kaushal, Binay Panjiyar

Subject: Medicine And Pharmacology, Clinical Medicine Keywords: T2DM; Early STIIT; Glycemic control

Online: 23 September 2024 (12:55:01 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1755.v1

The Relationship Between Feeling of Emptiness and Non-Suicidal Self-Injury in Borderline Personality Disorder Symptoms: The Mediating Role of the Inner Strengths

Piangdao Sripunya, Tinakon Wongpakaran, Nahathai Wongpakaran

Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: emptiness; non-suicidal self-injury; borderline personality disorder symptoms; five precepts; meditation; equanimity

Online: 23 September 2024 (12:54:49 CEST)

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Background and Objectives: Fifty percent of individuals with borderline personality disorder (BPD) experience Non-Suicidal Self-Injury (NSSI). One of the crucial factors related to NSSI is the feeling of emptiness. Although some inner strengths, such as five precepts, meditation, and equanimity, have been identified as potential buffers against negative mental health outcomes in BPD, their role in mediating the relationship between emptiness and NSSI is not well-documented. This study aimed to explore how these inner strengths mediate the relationship between feelings of emptiness and NSSI in individuals with BPD symptoms. Materials and Methods: A total of 302 participants with BPD symptoms completed several assessments: the SCID-II Personality Disorder (Borderline PD) to assess feelings of emptiness and NSSI, the Inner-Strength-Based Inventory (i-SBI) to evaluate five precepts, meditation, and equanimity, and the Outcome Inventory Depression (OI-Dep) to assess depression. Mediation analysis was performed using IBM SPSS and AMOS, with NSSI as the outcome variable, feelings of emptiness as the predictor, and the inner strengths as mediators. Results: The participants had a mean age of 36.56, with 65.4% being female. The analysis showed that five precepts, meditation, and equanimity significantly mediated the relationship between feelings of emptiness and NSSI, with a standardized coefficient of β = 0.534 (95% CI = 0.417 to 0.647, p < 0.001). The indirect effect of emptiness through these inner strengths was significant (β = 0.034, 95% CI = 0.009 to 0.075, p = 0.005). The mediation model explained 38% of the variance in NSSI with a 3% increase, albeit small but significant. Conclusions: The study highlights a negative mediating role of inner strengths in the relationship between feelings of emptiness and NSSI meaning that as these inner strengths increase, the direct impact of feelings of emptiness on NSSI decreases. This suggests that these inner strengths act as protective factors, reducing the likelihood that someone with feelings of emptiness will resort to NSSI as a coping mechanism. These findings suggest that targeting these inner strengths could be a valuable strategy in developing interventions aimed at reducing NSSI by addressing the underlying emotional challenges associated with BPD.

Preprint ARTICLE | doi:10.20944/preprints202409.1750.v1

Acute Gastric Dilatation Syndrome in New World Non-Human Primates

Mônica Sousa, Raoane S. Siqueira, Harlan H. L. Nascimmento, Telma S. Lima, Raquel A. F. Silva, Nayadjala T.A. Santos, Thiago F.L. Nery, Karoline L. Lacerda, Lilian R.C. Eloy, Inácio José Clementino, Ricardo B. Lucena

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: congestion; infection; management; monkey; stomach; sudden death

Online: 23 September 2024 (12:51:19 CEST)

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Preprint HYPOTHESIS | doi:10.20944/preprints202409.1731.v1

Hypertension-Tachycardia Duet in Acute Lymphoblastic Leukemia, Is It Due to Catecholamine Hypersecretion, Highlighting a Gap of Literature

Antoine AbdelMassih, Bann Khraisat, Christeen Sourial

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: ALL; catecholamine hypersecretion; Tachycardia-hypertension

Online: 23 September 2024 (12:28:47 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1692.v1

Association Between Nutrition-Related Indicators and Non-Alcoholic Fatty Liver Disease and Advanced Liver Fibrosis: Evidence from NHANES 2017–2020

Shouxin Wei, Sijia Yu, Ningbo Yang, Yindong Jia, Yunshen Lan

Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: NAFLD; AHF; nutritional status; NHANES; cross-sectional study

Online: 23 September 2024 (12:24:40 CEST)

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Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and its incidence has been rising in parallel with the prevalence of obesity and diabetes. A critical marker for the progression of NAFLD is advanced hepatic fibrosis (AHF), which can result in cirrhosis and hepatocellular carcinoma. This study sought to investigate the potential associations between five nutrition-related indices—the geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), controlled nutritional score (CONUT), triglyceride-total cholesterol-body mass index (TCBI), and albumin/globulin ratio (AGR)—and the progression of NAFLD and AHF. Methods: This study analyzed the association between five nutrition-related indicators and the occurrence of NAFLD and AHF by utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020.03. After adjusting for demographic, lifestyle, clinical, and laboratory-related factors, the associations were examined employing various statistical techniques, including multivariate logistic regression, subgroup analysis, and smooth curve fitting analysis. Results: This study included 5,514 subjects, of whom 2,088 were diagnosed with NAFLD and 359 with AHF. After adjusting for potential confounding factors using multivariate logistic regression analysis, the results revealed that GNRI, PNI, and TCBI were positively associated with the incidence of NAFLD, while CONUT and AGR demonstrated negative associations with NAFLD. Additionally, GNRI, CONUT, and TCBI were positively associated with the incidence of AHF, while AGR demonstrated a negative association with AHF.Conclusions: The study demonstrates that nutritional status plays a dual role in the progression of NAFLD and AHF, serving as both a risk and protective factor. These findings offer a scientific foundation for the early identification of high-risk populations and the development of individualized nutritional intervention strategies.

Preprint REVIEW | doi:10.20944/preprints202409.1685.v1

Revolutionizing Fine Needle Aspiration Cytology: The Transformative Power of Machine Learning in Image-Guided Sample Collection and Tumor Stratification

Mitesh Gupta

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Fine Needle Aspiration Cytology (FNAC); Machine Learning (ML); Deep Learning (DL); Image-Guided; ; BiopsyTumor Stratification; Diagnostic Accuracy; Artificial Intelligence (AI) in Oncology; Cytopathology; Predictive Analytics; Automated Diagnosis

Online: 23 September 2024 (12:23:07 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1687.v1

Ten-Year Observational Study of Patients with Lung Adenocarcinoma: Clinical Outcomes, Prognostic Factors, and Five-Year Survival Rates

Paweł Ziora, Paweł Kiczmer, Natalia Zaboklicka, Julia Wypyszyńska, Maria Stachura, Zuzanna Sito, Mateusz Rydel, Damian Czyżewski, Bogna Drozdzowska

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: lung adenocarcinoma; lung adenocarcinoma survival

Online: 23 September 2024 (12:17:36 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1705.v1

Bioactive and Its Chondroprotective Roles in Ameliorating Osteoarthritis: A Focus on Nanoparticle Therapy

Kota Sri Naga Hridayanka, Asim K. Duttaroy, Sanjay Basak*

Subject: Medicine And Pharmacology, Dietetics And Nutrition Keywords: Osteoarthritis; Epigenome; Nanoformulation; Bioactive; Polyphenol; Nanocurcumin; Non-coding RNA; Gut microbiota; Chondrocyte

Online: 23 September 2024 (12:15:06 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1713.v1

The Effects of Systemic Tranexamic Acid Administration on Drainage Volume, Duration of Drain Placement, and Length of Hospital Stay in Skin- and Nipple-Sparing Mastectomies with Immediate Expander-Based Reconstruction

Leon Guggenheim, Sara Magni, Armin Catic, Alberto Pagnamenta, Yves Harder, Daniel Schmauss

Subject: Medicine And Pharmacology, Surgery Keywords: tranexamic acid; systemic tranexamic acid; mastectomy; complications; drainage; expander

Online: 23 September 2024 (11:57:00 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1669.v1

The Impact of the Pdcd4, a Translation Inhibitor, on Drug Resistance

Qing Wang, Hsin-Sheng Yang

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: eIF4A; mTORC2-Akt pathway; β-catenin pathway; JNK pathway; paclitaxel; doxorubicin; fluorouracil; platinum-containing drug; IGF1R/IR inhibitor

Online: 23 September 2024 (11:53:36 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1673.v1

Myocarditis: Differences in Clinical Expression Between Patients with ST Segment Elevation in Electrocardiogram vs Patients Without ST Segment Elevation

Grytė Ramantauskaitė, Vaida Mizarienė, Kingsley A. Okeke

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: myocarditis; ST segment elevation; echocardiography; electrocardiogram

Online: 23 September 2024 (11:42:47 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1630.v1

Mesenchymal Stem Cells and Reticulated Platelets: New Horizons in multiple myeloma

Cristian Alejandro Mera-Azain, Johan Leandro Vargas-Pasquel, Sandra Milena Quijano-Gómez, Viviana Marcela Rodríguez-Pardo

Subject: Medicine And Pharmacology, Hematology Keywords: 1; Multiple Myeloma, 2; Mesenchymal stem cells, 3; Reticulated Platelets

Online: 23 September 2024 (10:02:41 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1649.v1

Review of Endodontic Instrumentation via Different Access Cavities – from Randomized In-Vitro Studies to Clinical Applications

Tomas Lang, Isabelle Steiner, Alexander Ditz, Karl W. Weich, Dinh Quoc-Viet Nguyen, Peter Gaengler

Subject: Medicine And Pharmacology, Dentistry And Oral Surgery Keywords: Endodontic instrumentation; Review; Angulated access; Minimally invasive endodontics; Root canal shaping; Volume loss; Clinical consequences

Online: 23 September 2024 (09:58:45 CEST)

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Abstract Aim: Micro-invasive therapeutic approaches in endodontics differentiate between different modified types of access cavities: occlusal via a smaller occlusal opening (15 ° access angle), medial (via the caries defect) for premolars and molars (30 ° access angle) and cervical with wedge-shaped defects or root caries on anterior teeth and single-rooted premolars (45 ° access angle). Therefore, the aim of this work was (i) to create an in-vitro model for the clinical simulation of these three different modified access types, (ii) to assess the biomechanics of the instrumentation and (iii) to measure the volumetric substance loss of four different preparation systems. Material and Method: Simulated S-shaped root canals with a high degree of obliteration (ISO 10) in acrylic polymer bodies with canal entrance angles of 15 °, 30 ° and 45 ° were shaped with NaOCl (3%) irrigation under clinical simulation at body temperature (37 ° C) in randomized blinded sequences (n = 7) according to manufacturer's instructions: 1. Conventional geometry, not heat treated, up to 35 / .04 (F360, Komet) 2. Conventional geometry, heat-treated, spark-eroded up to 40 / .04 (Hyflex EDM, Coltene Hyflex) 3. Spiral geometry, heat treated, up to 36 / .03 (TruNatomy, DentsplySirona) 4. Distinctive spiral geometry, heat-treated (XP-Endo Shaper, FKG) The vectorization (AutoCAD) of the root canals was performed before and after preparation in the apical, middle and coronal third of the root canal. The volumetric loss of substance in cubic millimeters was recorded and statistically evaluated using an independent two-sided t-test. Clinical demonstrations include three cases of micro-invasive access cavities as final proof of principle of fast and safe root canal treatment. Results The total loss of volume at 15 ° entry angles is significantly lowest with TruNatomy and XP Endo. With an access angle of 30 °, the total loss remains low and increases with F360 and Hyflex .. At a 45 ° access angle, the group differences remain: TruNatomy (6.5 mm3) and XP Endo (6.4 mm3) versus F360 (8.3 mm3) and Hyflex (8.4 mm3). This difference in loss of simulated root dentin is highly significant. Conclusions Conventional instruments achieve optimal shape of apical third of root canals at all entrance angles only with higher substance loss in coronal and middle thirds . In contrast, the spiral instrument geometry contributes to dentin protection and supports the concept of minimally invasive endodontics for lifelong tooth preservation as shown in four clinical cases.

Preprint REVIEW | doi:10.20944/preprints202409.1637.v1

A New Hope Against Antimicrobial-Resistance Wars: Cefiderocol

Gabriele Bianco, Matteo Boattini, Monica Cricca, Lucia Diella, Milo Gatti, Luca Rossi, Michele Bartoletti, Vittorio Sambri, Davide Gibellini, Rossella Fonnesu, Sara Comini, Paolo Gaibani

Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Antimicrobials; MultiDrug Resistance; Cephalosporins; PK/PD; Emerging Resistance

Online: 23 September 2024 (09:56:27 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1661.v1

Beyond the Surface: Cell Cycle Targeting in Skin Cancer Treatment

Sami Alrashed, Ali Nadi, Stephanie Dinescu, Alexander Rodzinka, Christopher Jaworski, Adam Bakos, Sami Tayfour, Jerry Tan, Eva Turley, Dorota Lubanska, Lisa Porter

Subject: Medicine And Pharmacology, Dermatology Keywords: skin cancer; cell cycle; CDK inhibitors; skin cancer stem cells

Online: 23 September 2024 (08:58:26 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202408.1541.v2

Advanced Delivery of Curcumin and Nicotinamide: Promising Solutions for Skin Infections and Melanoma

Omar Markab, Zainab Lafi, Naeem Shalan, Hala Al Daghistani, Ali Fahadawi, Razan Madi

Subject: Medicine And Pharmacology, Pharmacy Keywords: Natural compounds; melanoma; skin infection; synergism; liposomes

Online: 23 September 2024 (07:44:02 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1667.v1

Antioxidant Effects of Aromatic Plant Extracts in Neurodegenerative Diseases: A Review

Youyang Zhu, Miao Tian, Yuliang Qin, Ting Zhao, Zhaofu Li, Dongdong Qin

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Neurodegenerative diseases; Oxidative stress; Antioxidants; Aromatic plants extracts

Online: 20 September 2024 (20:20:02 CEST)

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Preprint REVIEW | doi:10.20944/preprints202409.1641.v1

BMD, CTX-1, and Osteocalcin as Monitoring Parameters of Bone Remodelling in CML Patients Undergoing Imatinib Therapy: From Basic Science to Clinical Perspective

Nurita Indarwulan, Merlyna Savitri, Ami Ashariati, Ugroseno Yudho Bintoro, Muhammad Noor Diansyah, Putu Niken Ayu Amrita, Pradana Zaky Romadhon

Subject: Medicine And Pharmacology, Hematology Keywords: Chronic Myeloid Leukemia; Bone Mineral Density; Bone Turnover; Tyrosine Kinase Inhibitor; CTX-1; Osteocalcin; Imatinib

Online: 20 September 2024 (15:06:17 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202409.1651.v1

Neuropsychiatric Adverse Events with Monoclonal Antibodies Approved for Multiple Myeloma: An Analysis from the FDA Adverse Event Reporting System

Giuseppe Cicala, Giulia Russo, Vincenza Santoro, Tindara Franchina, Nicola Silvestris, Mariacarmela Santarpia, Edoardo Spina, Maria Antonietta Barbieri

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Neuropsychiatric Adverse Events; Multiple Myeloma; FAERS; Monoclonal Antibody; Pharmacovigilance

Online: 20 September 2024 (14:58:48 CEST)

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Background/Objectives: Monoclonal antibodies (mAbs) have revolutionized multiple myeloma (MM) treatment. However, post-marketing data on their neuropsychiatric safety is limited. This study aimed to evaluate neuropsychiatric adverse events (AEs) related to mAbs used for MM through a retrospective pharmacovigilance analysis using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database. Methods: Individual case safety reports (ICSRs) from 2015 to 2023 with at least one neuropsy-chiatric AE and one of the MM-approved mAbs as the suspect drug (i.e., daratumumab, elo-tuzumab, isatuximab, belantamab mafodotin, teclistamab, elranatamab, and talquentamab) were analyzed using descriptive and disproportionality approaches. Results: Unknown signals of disproportionate reporting (SDR) included cerebral infarction for daratumumab (n = 45; reporting odds ratio (ROR) = 2.39, 95% confidence interval (CI) = 1.79-3.21; information component (IC) = 1.54, IC025-IC075 = 1.05-1.9), elotuzumab (25; 7.61, 5.13-11.28; 3.03, 2.37-3.51), and isatuximab (10; 2.56, 1.38-4.76; 1.67, 0.59-2.4); mental status changes for daratumumab (40; 2.66, 1.95-3.63; 1.67, 1.14-2.04) and belantamab mafodotin (10; 4.23, 2.28-7.88; 2.3, 1.22-3.03); altered state of consciousness for daratumumab (32; 1.97, 1.39-2.78; 1.32, 0.73-1.74) and belantamab mafodotin (6; 2.35, 1.05-5.23; 1.6, 0.19-2.52); Guil-lain-Barre syndrome (GBS) for daratumumab (23; 6.42, 4.26-9.69; 2.81, 2.11-3.3), isatuximab (8; 10.72, 5.35-21.48; 3.57, 2.35-4.37), and elotuzumab (3; 4.74, 1.53-14.7; 2.59, 0.52-3.8); and orthos-tatic intolerance for daratumumab (10; 12.54, 6.71-23.43; 3.75, 2.67-4.48) and elontuzumab (4; 28.31, 10.58-75.73; 5 , 3.24-6.08). Conclusions: Our analysis highlighted several previously unacknowledged SDRs for MM-approved mAbs. Given the complex and not entirely understood etiology of some neuropsy-chiatric AEs, including GBS, further investigations are necessary.

Preprint ARTICLE | doi:10.20944/preprints202409.1645.v1

Unexpected Hepatoprotective Effects of the Neuroproteсtor Lithium Ascorbate in a Model of a ʺWesternʺ Diet with Iron Overload and Multiple Organ Pathology

Ivan Torshin, Olga Gromova, Tatiana Bogacheva, Vadim Demidov, Vyacheslav Rastashansky

Subject: Medicine And Pharmacology, Gastroenterology And Hepatology Keywords: neuroprotectors; lithium therapy; fatty liver disease; animal models; hepatoprtection; iron overload; hemosiderosis; chemoinformatics; intelligent data analysis (data mining); lithium ascorbate

Online: 20 September 2024 (14:58:32 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202407.1675.v2

Participation of the Oxidative Stress in Aortic Valves Associated with Infective Endocarditis; Report of Three Cases

María Elena Soto, Linaloe Manzano-Pech, Verónica Guarner-Lans, Hugo Rodríguez-Zanella, Israel Pérez-Torres, Elizabeth Soria-Castro

Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Infective endocarditis; Oxidative stress; Cardiac valve; Antioxidant enzymes; Redox homeostasis

Online: 20 September 2024 (14:55:23 CEST)

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