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BioMed Research International

Wiley

Preprints posted in the last 90 days, ranked by how well they match BioMed Research International's content profile, based on 25 papers previously published here. The average preprint has a 0.11% match score for this journal, so anything above that is already an above-average fit.

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Prognostic Value of Mean Platelet Volume in Septic Shock: A Retrospective Cohort Study

Trujillo-Vega, F.; Lopez-Delgado, P. A.

2026-06-01 emergency medicine 10.64898/2026.05.29.26354453 medRxiv
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Abstract Background: Mean platelet volume (MPV) is a simple, low-cost biomarker that reflects platelet activation. Its prognostic value in septic shock remains controversial. We aimed to determine whether MPV at intensive care unit (ICU) admission is associated with hospital mortality in patients with septic shock. Methods: Retrospective cohort study of consecutive adults with septic shock (Sepsis-3 criteria) admitted to a single ICU. MPV, severity scores (SOFA, APACHE II, SAPS II), procalcitonin, and clinical data were collected. The primary outcome was in-hospital mortality. Spearman correlation, univariate and multivariate logistic regression (with Firth's correction), ROC curves, and subgroup analyses were performed. Results: Fifty-eight patients were included; mortality was 58.6%. MPV did not differ between non-survivors and survivors (13.09 {+/-} 1.37 vs. 12.66 {+/-} 1.45 fL, p = 0.259). MPV showed a weak correlation with procalcitonin ({rho} = 0.394, p = 0.002) but not with severity scores. In multivariate analysis adjusting for age, sex, SOFA and comorbidity count, MPV was not an independent predictor of mortality (OR 1.075, 95% CI 0.682-1.755, p = 0.749). The area under the ROC curve for MPV was 0.598 (95% CI 0.444-0.752), significantly lower than that of SOFA (0.837) and procalcitonin (0.836). Subgroup analyses showed no significant association between MPV and mortality in any stratum. Conclusions: In this cohort of septic shock patients, MPV at ICU admission was not associated with hospital mortality and had poor discriminative ability. Widely used severity scores and procalcitonin remain superior prognostic markers. MPV should not be used as a prognostic tool in septic shock. Keywords: Septic shock, Mean platelet volume, Mortality, SOFA, Procalcitonin, Biomarker

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Bordetella oligosaccharide (BOS) is associated with lipopolysaccharide of Bordetella petrii - the ancestor-related species of the pathogenic Bordetella

Koj, S.; Ucieklak, K.; Rojewska, O.; Niedziela, T.

2026-05-01 biochemistry 10.64898/2026.04.29.721566 medRxiv
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Bordetella produce a wide array of virulence factors. These factors are involved in bacterial colonization and evasion of immune defenses. Our recent studies revealed that the bacteria produce an exoglycan, Bordetella oligosaccharide (BOS). B. petrii is the evolutionary early divergent species of the genus Bordetella. This study has focused on the investigation of two B. petrii type strains: clinical and environmental. We employed nuclear magnetic resonance (NMR) analyses to elucidate the structural differences between their lipopolysaccharides. Our findings revealed that the LPS of clinical B. petrii strain comprises a hexasaccharide unit, that was structurally identical to the BOS. This form of LPS is only a minor population in the bacterial outer membrane of the environmental strain. In addition to the cell-bound BOS, its secreted glycoform was also found in growth media of B. petrii. Anti-BOS neoglycoconjugate antibodies cross-reacted with B. petrii LPS. This suggest that the newly identified BOS associated with B. petrii PS would be a potential vaccine element against Bordetella.

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Inflammatory Biomarkers & Interpretable ML for SAP Risk Stratification in AIS Patients Undergoing Bridging Therapy

Wang, X.-Y.; Li, M.-M.; Zhao, S.-M.; Jia, X.-Y.; Yang, W.-S.; Chang, L.-L.; Wang, H.-M.; Zhao, J.-T.

2026-04-17 neurology 10.64898/2026.04.15.26350997 medRxiv
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Stroke-associated pneumonia (SAP) is a major complication affecting the prognosis of acute ischemic stroke (AIS) patients who undergo intravenous thrombolysis followed by bridging mechanical thrombectomy (MT). Existing predictive tools are mostly subjective, and the value of combined biomarkers and interpretable machine learning (ML) models in this specific population remains unclear. This study aimed to construct an interpretable ML model to predict SAP risk in AIS patients undergoing bridging therapy, and to identify key predictive factors using Shapley Additive Explanations (SHAP). A single-center retrospective observational study was conducted on 135 AIS patients who received intravenous thrombolysis followed by bridging MT at Xinxiang Central Hospital from January 2019 to December 2023. Clinical data, laboratory indicators (including neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], systemic immune-inflammation index [SII], and systemic inflammatory response index [SIRI]) were collected. LASSO regression was used for feature selection, and ten ML models were constructed to predict SAP. The optimal model was selected based on area under the receiver operating characteristic curve (AUC-ROC) and decision curve analysis (DCA), and SHAP analysis was applied to interpret the model. Among 135 included patients, 70 (51.9%) developed SAP. LASSO regression selected 11 key variables associated with SAP. The CatBoost model showed the best performance, with an AUC of 0.952 in the training set and 0.932 in the test set. SHAP analysis revealed that the 7-day National Institutes of Health Stroke Scale (NIHSS_7d), 24-h SIRI (SIRI_24h), and 24-h white blood cell count (WBC_24h) were the top three factors contributing to SAP prediction. Dynamic detection showed that 24-h and 48-h NLR, 24-h SII, and 24-h and 48-h SIRI were significantly higher in the SAP group than in the non-SAP group (all P < 0.05), while no significant difference in PLR was observed between the two groups. Inflammatory biomarkers (24-h NLR, 24-h SII, 24-h SIRI, 48-h NLR, 48-h SIRI) are closely associated with SAP in AIS patients undergoing bridging therapy. The interpretable CatBoost model constructed with LASSO-selected variables exhibits high predictive value for SAP, which can help clinicians identify high-risk patients early and guide personalized treatment.

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Identification of key genes involved in neuroendocrine regulation in pulpitis: bioinformatics and experimental analysis

Jin, H.; Wang, Y.; Sun, A.; Liu, Y.; Guo, T.

2026-04-20 dentistry and oral medicine 10.64898/2026.04.18.26351158 medRxiv
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BackgroundThere is a close correlation between neuroendocrine regulation and pulpitis progression. This study aims to identify key neuroendocrine regulation-related genes in pulpitis, providing insights for its treatment. MethodsGSE77459 and GSE92681 datasets were used to validate experimental findings. Key neuroendocrine regulation-related genes were identified via Cytoscape plugin cytoHubba and expression validation. Gene set enrichment analysis, RNA-binding protein regulatory networks, post-translational modifications, molecular regulatory networks, and drug prediction were performed. Key gene expression was experimentally verified in clinical samples. ResultsTop 10 genes were obtained via cytoHubba; 4 (IL6R, OSM, IL1RN, CCL4) with significant differences between pulpitis and control samples and consistent trends in both datasets were identified as key genes. Gene set enrichment analysis showed key genes participate in pathways like cytokine-cytokine receptor interaction. Related RNA-binding proteins were ELAVL1 and HNRNPA1, with phosphorylation as the main post-translational modification. Core regulatory microRNAs included miR-519, miR-765, miR-23, and regulatory factors included FOXC1, PRRX2. Targeted drugs (e.g., sarilumab, haloperidol decanoate, cyclosporine) were predicted, and clinical sample verification confirmed consistent expression trends. Conclusion4 key neuroendocrine regulation-related genes were identified, which may have clinical significance for the diagnosis and treatment of pulpitis.

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The efficacy and safety of argatroban with clopidogrel versus aspirin with clopidogrel for acute minor ischemic stroke (ACAP): study protocol for a multicenter, randomized controlled trial

Zhang, H.; Ma, X.; Xiao, Y.; Liao, G.; Kong, N.; Qin, T.; Huang, M.; Yin, Z.; Chen, W.; Wu, J.; Xian, J.; Fu, J.; Xie, F.; Jin, C.; Liao, Z.; Liang, W.; Lin, L.; Xian, W.; Nguyen, T. N.; Wang, D.; Zhong, W.

2026-03-31 neurology 10.64898/2026.03.30.26349790 medRxiv
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Background: Previous studies have shown the benefit of dual antiplatelet therapy (DAPT) for acute minor ischemic stroke. Argatroban, is a thrombin inhibitor and is primarily used in patients with acute ischemic stroke experiencing early neurological deterioration. There is no study about the benefit of antiplatelet plus anticoagulant in this population. We aim to study the difference between the combination of argatroban and clopidogrel and DAPT in the outcomes of patients with acute minor ischemic stroke (AMIS, NIHSS <5) presenting within 72 hours after onset. Methods: Argatroban combined with clopidogrel versus aspirin combined with clopidogrel in Stroke (ACAP study) is an investigator-initiated, multicenter, prospective, randomized, open-label trial with blinded endpoint evaluation conducted at four centers in China. This trial will randomize 464 eligible patients with minor ischemic stroke of NIHSS 5 (232 in each arm) within 72 hours of the last known well to receive intravenous argatroban with clopidogrel (treatment group) or aspirin plus clopidogrel (control group). The primary outcome is the proportion of patients achieving excellent outcome, defined as a score of 0-1 on the modified Rankin scale, at 90 days. Conclusions: The ACAP trial will provide important data on the role of intravenous argatroban in patients with acute minor ischemic stroke presenting within 72 hours of last known well.

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Isoquercetin treatment of mouse sickled red blood cells shows a discernible deformability and sickling phenotype

Owegie, O. C.; Hancco Zirena, I.; Penubothu, T.; Ghiran, I. C.; Yang, M.

2026-04-28 pharmacology and toxicology 10.64898/2026.04.24.720679 medRxiv
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IntroductionSickle cell disease is an inherited hemoglobinopathy with defective red cell deformability. The defective deformability promotes microvascular occlusion and subsequent vaso-occlusion in sickle cell disease patients. Previous studies have demonstrated that thiol isomerases, an endoplasmic reticulum-resident oxidoreductase that is released from vascular cells into the bloodstream, are present on red cell membrane and contribute to cellular dehydration and sickling. However, the role of membrane-bound thiol isomerases on sickled red blood cells is unclear. MethodsUsing red blood cells from Townes humanized sickle cell or non-sickled mice, we performed ektacytometry assay under shear using laser assisted optical rotational cell analyzer (LORRCA) to assess the effects of antagonizing thiol isomerases with isoquercetin and a functional blocking monoclonal antibody. The densitometric properties of sickled red blood cells in the presence of isoquercetin was also tested using magnetic levitation. ResultsThiol isomerase antagonism increased sickled red cell elongation, cellular dehydration and the diamagnetic signature compared to control treatment. ConclusionThiol isomerases may be involved in regulating sickled red blood cells mechanical properties through mechanisms that require further investigation.

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Fucoidan from brown algae Laminaria japonica trigger apoptosis in colon cancer cells

Shimabukuro, K.; Miyagi, I.; Harashima, N.

2026-06-03 cancer biology 10.64898/2026.05.31.728131 medRxiv
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In many cases, cancer cells develop resistance to chemotherapy and other cancer treatments. Therefore, there is a need for new therapeutic agents using naturally derived compounds that are expected to have low toxicity and fewer side effects. Fucoidan is a sulfated polysaccharide found in brown algae such as kelp and wakame seaweed. Many previous reports have shown that fucoidan exerts anti-bacterial, anti-viral, antioxidant, immunomodulatory effects, and anti-tumor effects. The antitumor and antiviral effects of fucoidan have been reported to vary depending on its origin, as they are influenced by sulfate content and molecular weight. Therefore, it is important to investigate the antitumor effects of various species of fucoidan, but there are few reports on the effects of fucoidan derived from Laminaria japonica on colorectal cancer. In this study, we evaluated the effects of fucoidan from Laminaria japonica on apoptosis in five human colon cancer cells. The apoptotic cell population was significantly increased in fucoidan-treated cells. In addition, the expressions of Bax, Bak, PARP, caspase-8, -9 and -3 were upregulated. The necroptosis-related molecule RIP and MLKL were degraded indicates that necroptosis was not involved in this fucoidan-treated cell death. These results suggest that fucoidan-treated cells showed induction of apoptosis via mitochondrial intrinsic pathway, but not necroptosis via caspase-8. Fucoidan-induced apoptosis may prove useful in the therapeutic protocol of colon cancer.

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WITHDRAWN: Integrative Transcriptomic Analysis Identifies Hypoxia-Responsive Cell Cycle Hub Genes as Prognostic Markers in Glioblastoma

Sharma, M. K.; Chongtham, J.; Bhushan, A.; Chosdol, K.; Sinha, S.; Srivastava, T.

2026-05-12 cancer biology 10.1101/2025.10.18.683218 medRxiv
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Glioblastoma (GBM) is the most aggressive primary brain malignancy, characterized by hypoxia-driven proliferation, therapeutic resistance, and poor prognosis. While hypoxia-induced transcriptional changes are well documented, the temporal regulation of cell cycle genes under sustained hypoxia remains unclear. This study profiled transcriptomic alterations in U87MG cells cultured under normoxia and graded hypoxia for one to three days. Differentially expressed genes (DEGs) were identified and analyzed using STRING, Cytoscape, MCODE, and CytoHubba to construct protein-protein interaction (PPI) networks and extract hub genes. Functional enrichment was assessed through DAVID, ClueGO, and KEGG, while prognostic relevance was evaluated using GlioVis and ONCOMINE datasets. qRT-PCR validated expression of selected hub genes. A total of 294 DEGs were identified, forming two main functional modules enriched in cell cycle regulation and chemokine signaling pathways. Eighteen hub genes (KIF20A, CCNB1, AURKA, EGR1, CDCA3, CENPF, CDCA2, ASPM, KIF11, CCL2, CCNA2, DLGAP5, RACGAP1, TPX2, PTGS2, CTGF, and KIFC1) were significantly associated with mitotic processes and GBM progression. Survival analysis demonstrated that 17 of these genes correlated with poor overall survival (p < 0.05). qRT-PCR confirmed that hub gene expression peaked during early hypoxia and declined with prolonged exposure, indicating dynamic regulatory adaptation. These findings identify key hypoxia-responsive genes governing cell cycle progression and highlight their prognostic and therapeutic potential in glioblastoma.

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Red/near-infrared light activates the mitochondrial large-conductance calcium-activated potassium channel in glioblastoma cells.

Bednarczyk, P.; Lewandowska, J.; Kulawiak, B.; Szewczyk, A.

2026-04-05 biochemistry 10.64898/2026.04.02.716077 medRxiv
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Mitochondrial potassium channels, located in the inner mitochondrial membrane, play a crucial role in the cells life/death phenomenon. Activation of mitochondrial potassium channels by potassium channel openers may protect cells against ischemia-reperfusion injury. It is known that mitochondrial large conductance calcium-activated potassium channels interact with various mitochondrial proteins, including enzymes of the respiratory chain. Numerous studies indicate that the mitochondria, especially cytochrome c oxidase, play a crucial role as a chromatophore in the cellular response to red and near-infrared light. In this study, we employ the patch-clamp technique and single-channel recordings to investigate the regulation of glioblastoma mitochondrial large conductance calcium-activated potassium channel activity by infrared light. Specifically, we examined the effects of wavelengths 620 nm, 680 nm, 760 nm, and 820 nm in a redox-controlled environment. Our findings suggest that illuminating the inner mitochondrial membrane with these wavelengths may activate mitochondrial large conductance calcium-activated potassium channels. These results offer new insights into the regulation of mitochondrial potassium channels by cytochrome c oxidase, which may lead to the development of non-pharmacological interventions with potential cytoprotective benefits.

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N-3 Polyunsaturated Fatty Acids Ameliorate Post-infarction Cardiac Dysfunction Through Modulation Of Adiponectin-Ceramide Metabolism

Liu, Y.; Sun, W.; Liu, J.; Wu, H.; Liu, P.; Chen, Y.; Zhang, R.; Chen, W.; Wang, S.; Guo, X.; Zhang, W.; Cao, L.

2026-04-16 pharmacology and toxicology 10.64898/2026.04.13.718333 medRxiv
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BackgroundIt has been shown that n-3 polyunsaturated fatty acids (n-3 PUFA) of marine origin exert significant beneficial effects on myocardial infarction (MI); however, the underlying mechanisms remained unclear. Ceramides play a vital role in the regulation of energy metabolism, mitochondrial function, and apoptosis. Through the integration of clincial studies and animal experiments, this study aimed to determine whether n-3 PUFA improved myocardial function by modulating ceramide metabolism. MethodsIn a case-control study, 100 patients with AMI and 100 healthy pariticipants were enrolled to measure serum ceramide concentrations. Meanwhile, mice were randomly allocated into 4 groups and administrated to a 3-week intervention with n-3 PUFA in triglyceride and phospholipid forms. A mouse model of MI was then established, followed by an additional 4 weeks of continuous intervention. Subsequent comprehensive assessments of cardiac function were performed in the mice. Finally, the mice were euthanized to conduct targeted ceramide lipidomic analysis and other relevant assays. ResultsThe levels of serum C16:0-, C18:0-, C20:0-, C24:1-ceramides and total ceramides in patients with acute myocardial infarction (AMI) were significantly higher compared with the healthy controls. In the murine model of myocardial infarction, pathological analysis via TTC staining demonstrated that interventions with fish oil (triglyceride form) and krill oil (phospholipid form) both significantly reduced myocardial infarct size. Concomitant echocardiographic assessment confirmed that both treatments markedly elevated left ventricular ejection fraction (LVEF), with the magnitude of improvement being significantly superior to that of the model control group. Concurrently, compared with the model group, the concentrations of ceramides in cardiac tissue and serum were significantly lower in the groups with fish oil and krill oil intervention. Western blot analysis further confirmed that n-3 PUFA intervention upregulated adiponectin expression, reduced ceramide accumulation in myocardial tissue, and inhibited mitochondria-mediated cardiomyocyte apoptosis, thereby improving cardiac function and prognosis following myocardial infarction. ConclusionsThis work demonstrates that n-3 PUFA exert cardioprotective effects following MI mediated by adiponectin-ceramide axis. However, there is no significant difference regarding therapeutic efficacy of n-3 PUFA in triglyceride or phospholipid forms.

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Targeted Binding of Nitrogenous Waste Products Using Antibody-Coated Granules: A New Approach for CKD Management

Abdelaziz, S. S.; Mubarki, A.; Salah, M. S.

2026-05-05 nephrology 10.64898/2026.04.28.26351724 medRxiv
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Chronic kidney disease is a progressive condition characterized by the accumulation of nitrogenous waste products, including urea, creatinine, and uric acid, leading to significant morbidity in advanced stages. Current management strategies, such as dialysis, are effective but associated with substantial clinical and socioeconomic burdens, highlighting the need for alternative approaches to reduce circulating toxins. In this study, we evaluated a novel formulation of psyllium-based granules functionalized with specific antibody combinations targeting urea, creatinine, and uric acid. The aim was to assess the biochemical effects, as well as the binding and sequestration efficiency, of these formulations under controlled experimental conditions. A randomized, double blind controlled in vitro study was conducted using serum samples obtained from twenty patients with uremia undergoing dialysis. Three formulations, labeled S1, S2, and S3, were evaluated. All tested formulations resulted in statistically significant reductions in urea, creatinine, and uric acid concentrations compared with baseline values. Among them, the S1 formulation demonstrated the highest binding efficiency, reducing urea by 70% {+/-} 7%, creatinine by 80% about 4%, and uric acid by 52% about 11%. Linear regression analysis confirmed a statistically significant association between the S1 formulation and reductions in these biochemical parameters. These findings suggest that antibody functionalized granules can effectively bind and sequester nitrogenous waste products under in vitro conditions. This approach may represent a potential strategy for reducing uremic toxin burden, either as a complementary method or as a future alternative to existing renal replacement therapies. Further studies, including in vivo validation, dose optimization, and controlled clinical trials, are required to establish safety, efficacy, and translational applicability.

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Comparative Effects Of Flaxseed Supplementation On Hematological Parameters, Lipid Profile And Immunity Of Male Rabbit

Kanwal, A.; Iqbal, R.; Farhan, F.; Kanwal, A.

2026-04-08 zoology 10.64898/2026.04.06.716729 medRxiv
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Flaxseeds have high nutritive value due to the presence of proteins, lignins (SDG), fatty acids, vitamins, dietary fibers, minerals and carbohydrates. This research was conducted to evaluate the effect of distinct doses of flaxseeds on hematological parameters, immunity and lipid profile of male rabbit. In this research, 60 male rabbits were isolated into four groups, three treatment groups T1, T2 and T3 and a control group T0, with 15 rabbits in each group. The treatment groups were given 4%, 6% and 8% of flaxseeds per daily diet for 45 days. On 15th, 30th and 45th day of experiment, blood samples were collected to examine their hematological parameters. Serum was separated from the collected blood sample to perform ELISA and serum lipid profile test to assess antibody titer and lipid profile of the rabbits respectively. The results indicated a significant reduction in TC, TG, and LDL-C levels in contrast to HDL-C which increased significantly in all treatment groups. Whereas, the statistical analysis of hematological parameters showed an HSD (p[&le;]0.05) in flaxseed treated groups. A maximum level of Hb, WBCs, RBCs, MCHC, MCV, HCT, MCH and differential leukocytes count was recorded in high dose group T3 (8% flaxseeds) followed by medium dose group T2 (6% flaxseeds) and low dose group T1 (4% flaxseeds) respectively. There was a significant rise in antibody titer (p[&le;]0.05) against RHDV (Rabbit Hemorrhagic Disease Virus) comparable to non-treated group. The outcomes illustrated that flaxseeds as nutritional supplement are undoubtedly beneficial to health and prevent various diseases. Study contributionThis research specifically explores how dietary supplementation with flaxseeds, a widely recognized source of omega-3 fatty acids, fiber, and antioxidants, can influence metabolic health and immune function. These findings have significant implications for nutritional interventions aimed at improving cardiovascular health, immune support, and overall well-being, making it highly relevant to the journals readership. The aim of this study was to investigates the dose-dependent effect of flaxseeds on hematological parameters, lipid profile and immunity of male rabbits. Using a controlled experimental design, male rabbits were fed a diet supplemented with varying doses of flaxseeds over a period of 45 days. Key parameters such as total cholesterol, triglycerides, LDL-C, HDL-C, antibody titer, red, white blood cell, platelet counts, Hb, HCT, MCV. MCHC, MCH and differential leukocytes levels were measured to assess the impact of flaxseeds. The results demonstrated that flaxseed supplementation significantly restored lipid profiles by reducing total cholesterol and triglycerides, LDL-C and increasing HDL-C while also enhancing immune function by rising antibody titer and maintaining healthy blood profiles in the subjects.

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DKK1 and CKAP4 expression is associated with cervical lymph node metastasis in tongue squamous cell carcinoma

Fujita, H.; Takahashi, O.; Yada, N.; Tanaka, J.; Haraguchi, K.; Morioka, M.; Yaginuma, T.; Sasaguri, M.; Kokabu, S.; Habu, M.

2026-06-01 dentistry and oral medicine 10.64898/2026.05.29.26354440 medRxiv
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Objective: To identify Dickkopf-1 (DKK1) as a prognostically relevant candidate in head and neck squamous cell carcinoma and to evaluate whether DKK1 and cytoskeleton-associated protein 4 (CKAP4) expression is associated with cervical lymph node metastasis in tongue squamous cell carcinoma (TSCC). Methods: DKK1 was screened using the Human Protein Atlas Pathology Atlas. Immunohistochemical expression of DKK1 and CKAP4 was examined in 54 patients with primary TSCC (cT1-4N0) treated surgically between 2015 and 2020. Nine cases were excluded because of insufficient tissue blocks or inadequate staining quality, leaving 45 evaluable cases. Associations with delayed cervical lymph node metastasis were assessed together with conventional clinicopathological factors, including infiltrative growth pattern (INF) and pathological depth of invasion (pDOI). Results: In public database analysis, high DKK1 expression was associated with poorer overall survival in head and neck squamous cell carcinoma. In the TSCC cohort, pDOI [&ge;]5 mm and INF pattern c were significantly associated with cervical lymph node metastasis. Positive DKK1 and CKAP4 expression were also significantly associated with cervical lymph node metastasis. Furthermore, combined DKK1/CKAP4 positivity, when incorporated with INF and pDOI, provided additional risk stratification, and cases with all 3 factors showed a markedly increased likelihood of cervical lymph node metastasis. Conclusions: Expression of DKK1 and CKAP4 was associated with cervical lymph node metastasis in TSCC. Combined assessment of DKK1/CKAP4 expression with INF and pDOI may improve pathological risk stratification and may help identify patients who require closer neck evaluation and postoperative management.

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A new species of Rana from Anhui, China (Anura, Ranidae)

He, Z.; Wang, S.; Wu, S.; Bai, Y.; Wei, J.; Li, Y.; Li, H.; Liu, Y.; Li, X.; Wu, X.; Wang, S.

2026-04-24 zoology 10.64898/2026.04.24.720648 medRxiv
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The diversity of the brown frog genus Rana may be underestimated as the high similarity of morphological characters. A new species belonging to the genus Rana is delineated based on eight specimens obtained from the Tianma National Nature Reserve, Jinzhai County, Luan City, Anhui Province, China. The phylogenetic analysis based on three mitochondrial genes (12S, ND2, and Cyt b) and one nuclear gene (BDNF) showed that the new species formed an independent clade closely related to R. culainensis and received strong support. In addition, morphological differentiation confirmed the phylogenetic results, and both supported the validity of a new species (Rana tianmaensis sp. nov.) in the R. japonica species group. The discovery of this new species enhances peoples understanding of the biodiversity of Rana and can provide important foundational data for scientific decision-making on protected area construction, ecological conservation, and species diversity. With the inclusion of newly described species in this study, the distribution of Rana genus in China now includes 31 recognized species.

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Multidimensional Mechanistic Study of Panax Notoginseng Saponins in the Treatment of Alcohol-Induced Osteonecrosis of the Femoral Head: Integrating Network Pharmacology, Molecular Dynamics Simulation and In Vivo Validation

Bai, R.; Su, H.; Mo, J.; Zhang, X.; Li, Z.; Chen, X.; Ye, S.; Nie, X.; Chen, S.; Liang, B.

2026-04-30 pharmacology and toxicology 10.64898/2026.04.28.721283 medRxiv
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BackgroundAlcohol-induced osteonecrosis of the femoral head (AIONFH) is an orthopedic disorder from chronic alcohol abuse, characterized by disrupted femoral head blood supply, osteocyte death and structural collapse. Current hip-preserving therapy is unsatisfactory, and most patients eventually require total hip arthroplasty. Panax Notoginseng Saponins (PNS), the core active component of Panax notoginseng, exerts pro-angiogenic and anti-osteocyte apoptosis effects, but its specific therapeutic mechanism remains unclear. ObjectiveThis study used network pharmacology, molecular dynamics simulation and animal experiments to identify PNSs active components, core targets and key pathways for AIONFH, verify its in vivo efficacy, and provide a scientific basis for clinical application. MethodsPNS active components, their targets and AIONFH-related targets were screened from databases; intersection targets constructed an interaction network, core targets were screened by three machine learning algorithms, with concurrent GO and KEGG analysis. Molecular docking was performed between core targets and PNS components; Gromacs 2022 conducted 100 ns simulation to evaluate complex stability. AIONFH rat models were grouped with 4-week intragastric intervention; pathology, immunofluorescence and PCR were used for detection. Results and DiscussionNetwork pharmacology identified 127 PNS targets and 18 intersections with 672 AIONFH targets. Six core targets (including FGF2, HSD11B1) were screened; KEGG indicated VEGF pathway as key. Ginsenoside Re bound HSD11B1 with the lowest binding energy (-12.4 kcal/mol), and 100 ns simulation confirmed complex stability. Animal experiments showed PNS improved trabecular structure and regulated osteocyte activity. PNS treats AIONFH via multi-component, multi-target mode, core mechanism being osteocyte apoptosis inhibition. Results and DiscussionNetwork pharmacology screening identified 127 potential targets of PNS, and 18 potential intersection targets were obtained by overlapping with 672 AIONFH-related targets. Six core targets including FGF2 and HSD11B1 were screened out by machine learning, and KEGG analysis indicated that the VEGF pathway and other pathways were the key signaling pathways for PNS action. Molecular docking showed that Ginsenoside Re had the lowest binding energy with HSD11B1 (-12.4 kcal/mol), and 100 ns molecular dynamics simulation confirmed the stable conformation of this complex. Animal experiments demonstrated that PNS could improve trabecular bone structure and regulate osteocyte activity. In summary, PNS exerts a therapeutic effect on AIONFH through a multi-component, multi-target and multi-pathway mode, with the core mechanism of inhibiting osteocyte apoptosis.

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ECG spectrogram-based deep learning model to predict deterioration of patients with early sepsis at the emergency department: a study from the Acutelines data- and biobank

van Wijk, R. J.; Schoonhoven, A. D.; de Vree, L.; Ter Horst, S.; Gaidhane, C.; Alcaraz, J. M. L.; Strodthoff, N.; ter Maaten, J. C.; Bouma, H. R.; Li, J.

2026-03-27 emergency medicine 10.64898/2026.03.26.26349371 medRxiv
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Purpose: Early recognition of deterioration in patients with suspected infection at the emergency department (ED) is important. Current clinical scoring systems show limited discriminative performance for early deterioration. Continuous electrocardiogram (ECG) recordings may offer additional dynamic physiological information that can enhance early prediction of deterioration in patients with suspected infection. Methods: We developed a multimodal, ECG-derived spectrogram-based pipeline to predict deterioration within 48 hours of ED admission. We used the first 20 minutes of ECG recordings for the spectrograms. We compared the model with the National Early Warning Score (NEWS), quick Sequential Organ Failure Assessment (qSOFA), a baseline model with vital parameters, sex, and age, and a Heart Rate Variability (HRV) derived model. Results: In this study, 1321 patients were included, of whom 159 (12%) deteriorated. The multimodal model combining baseline data with spectrograms showed the best overall performance, with an Area Under the Receiver Operating Characteristic (AUROC) of 0.788, followed by the baseline model (age, sex, triage vitals) alone, with an AUROC of 0.730. The HRV-only model and the qSOFA showed the lowest performance (AUROC 0.585 and 0.693, respectively). Conclusion: This study shows that ECG-derived multimodal spectrogram models outperform those based solely on vital signs and HRV features, as well as established clinical scores such as NEWS and qSOFA. Spectrogram analysis represents a promising approach to enhance early risk stratification and support clinical decision-making for patients with suspicion of infection in the ED.

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Dynamics Of C-Reactive Protein In The Early Postoperative Period As A Predictor Of Infectious Complications And A Tool For Optimizing Antibiotic Therapy

Ochakovskaya, I. N.; Onopriev, V. V.; Dovlatbekyan, N. M.; Zhuravleva, K. S.; Zamulin, G. Y.; Durleshter, V. M.

2026-04-07 infectious diseases 10.64898/2026.04.06.26350253 medRxiv
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Objective. To evaluate the diagnostic and prognostic significance of C reactive protein (CRP) level dynamics within the first five days after surgery for the early detection of surgical site infections (SSI) and to identify independent risk factors, taking into account regional specifics of surgical management (types of surgeries, duration of procedures), as well as the local hospital microbial landscape. Materials and Methods. A single-center retrospective cohort analysis of data from 127 patients who underwent surgical procedures between 2022 and 2024 was conducted. CRP levels on postoperative days 1, 3, and 5 were assessed, and delta values were calculated. Descriptive statistics, ROC analysis, and multivariate logistic regression were used to identify predictors of SSI. Results. Patients with SSI lacked the physiological decrease in CRP levels by day 5. The most informative indicator was the CRP level on day 3: a threshold of >106 mg/L was associated with a high risk of SSI (AUC=0.76; sensitivity 85%, specificity 63%). Independent predictors of SSI included surgery duration (OR=1.015 per 1 min; p<0.001) and the increase in CRP between days 3 and 5 (delta CRP3-5: OR=1.027; p=0.023). A combined model (clinical parameters + CRP) demonstrated the highest predictive ability (AUC=0.79). Conclusion. Monitoring CRP dynamics, particularly on days 3 and 5, is a highly informative and accessible method for the early diagnosis of SSI. A CRP threshold of >100 mg/L on day 3 and its subsequent increase should serve as a trigger for in-depth diagnostic investigation and rationalization of antimicrobial therapy. Keywords: C reactive protein, postoperative complications, surgical site infection, antibiotic therapy, predictive factors, diagnosis

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Efficacy evaluation of glasedgib Sonic Hedgehog pathway inhibition with or without inotuzumab in B-ALL cells using a new co-culturing system model and a validated chemosensitivity assay

Woolston, D. W.; Churchill, M.; Grandori, C.; Advani, A.; Yeung, C. C. S.

2026-05-12 cancer biology 10.64898/2026.05.07.723573 medRxiv
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PurposeGlasdegib is a Sonic Hedgehog (SHH) pathway inhibitor used for treating newly diagnosed acute myeloid leukemia in elders or patients unfit for intensive chemotherapy. This study sought to demonstrate growth inhibition and increased apoptosis of B-cell acute lymphoblastic leukemia (B-ALL) in vitro under glasdegib, alone and combined with inotuzumab, using a novel co-culture system and validated chemosensitivity testing model to determine whether glasdegib with and without inotuzumab may represent a promising treatment strategy in B-ALL. MethodsSeven blood and marrow samples from B-ALL patients were co-cultured with HS-5 stromal cells in a co-culturing system designed to mimic the tumor microenvironment to maintain B-ALL cell viability for chemosensitivity testing under glasdegib and inotuzumab. ResultsCo-culturing improved B-ALL viability from four to nine days. Dosage-dependent responses to glasdegib were consistent among B-ALL samples on day four based on culture viability, and varied based on expressions of SSH genes GLI1, GLI3, SMO, and PTCH1. Combination with inotuzumab had varied effects on treatment response. ConclusionCo-culturing B-ALL cells with HS-5 stromal cells improves B-ALL growth and viability. Glasdegib with and without inotuzumab treatments impact the viability of co-cultured B-ALL cells by day four. SHH gene expressions suggest different B-ALL patients may be sensitive or resistant to glasdegib and inotuzumab.

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Smartphones vs DSLR Cameras in Dental Photography: An In Vitro Assessment of Linear Dimensional Shift in the Esthetic Zone

Boontharak, A.; Amornsettachai, P.; Visuttiwattanakorn, S.

2026-03-24 dentistry and oral medicine 10.64898/2026.03.20.26348950 medRxiv
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The in vitro study aimed to evaluate linear dimensional shifts in intraoral photographs of the esthetic zone captured using two smartphone cameras--the iPhone 15 Pro Max and the Samsung Galaxy S23 Ultra--compared to a digital single-lens reflex (DSLR) camera, which is regarded as the gold standard for dental photography. Imaging was performed under controlled conditions using a custom-designed stand and stabilizer to maintain a consistent distance and angle between the dental model and the photographic devices. Standardized frontal and occlusal images of the anterior maxillary region were acquired, and point-to-point linear measurements between specified dental landmarks were performed using calibrated digital imaging software. Each measurement was conducted triple and then averaged across various samples per image to guarantee precision and dependability. Friedmans test with Bonferroni correction was applied for statistical analysis to evaluate differences among the imaging devices. The results indicated no statistically significant variations in linear measures between the DSLR and the Samsung Galaxy S23 Ultra (p > 0.05), however minor inconsistencies were noted between the DSLR and the iPhone 15 Pro Max. It is important to acknowledge that all images were obtained utilizing the stabilization system, which contrasts with the conventional handheld approach applied in clinical environments and could impact the external validity of the results. The Samsung Galaxy S23 Ultra, in telephoto mode, demonstrated measurement precision similar to that of a DSLR camera, potentially serving as a reliable choice for clinical intraoral photography. The iPhone 15 Pro Max demonstrated potential, although minor measurement discrepancies.

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Integrated Clinical and Network Pharmacology Study Reveals the Efficacy and Multi-Target Mechanism of Shenfu Injection in Septic Shock

Shi, Y.; Zhang, B.; Tian, Y.; Liu, Q.; Zhou, X.

2026-03-25 emergency medicine 10.64898/2026.03.20.26348945 medRxiv
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Background The high mortality of septic shock demands novel adjunctive therapies. Shenfu Injection (SFI), a traditional Chinese medicine, shows potential but its mechanism remains unclear. Method s We conducted an open-label, randomized trial in 80 patients with septic shock. Patients received standard care with or without adjunctive SFI for 7 days. The primary outcome was 28-day mortality. Key secondary outcomes included inflammatory markers, lactate clearance, and vasopressor duration. Concurrently, network pharmacology analyzed SFIs bioactive components, predicted targets, and enriched pathways, with validation by molecular docking. Results The 28-day mortality was significantly lower in the SFI group (20.0% vs. 42.5%, P=0.030). SFI accelerated clinical improvement, evidenced by greater reductions in IL-6 and procalcitonin, higher 6-hour lactate clearance (35.2% vs. 18.5%, P<0.001), shorter vasopressor duration (48 vs. 72 hours, P<0.001), and more rapid SOFA score decline. Network pharmacology identified 145 SFI-septic shock common targets, with IL-6, SRC, and MAPK3 as central hubs. Pathway analysis revealed significant enrichment in TNF, PI3K-Akt, and IL-17 signaling pathways. Molecular docking confirmed strong binding of key SFI components (e.g., Ginsenoside Rh2) to core targets like IL-6. Conclusion s Adjunctive Shenfu Injection reduces mortality and improves clinical recovery in septic shock, potentially through a multi-target mechanism involving modulation of inflammatory and cellular signaling pathways. This integrative study provides both clinical evidence and a mechanistic framework supporting SFI's use. Clinical Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800020435.