bluuebunny/crossref_metadata_2025 huggingface dataset:
The Burden of Irritable Bowel Syndrome and Functional Dyspepsia in Poland: A Cross- Sectional Study from West Pomeranian Voivodship
Authors: Krynicka Patrycja , Kaczmarczyk Mariusz , Skonieczna-Żydecka Karolina , Cembrowska Danuta , Podsiadło Konrad , Dąbkowski Krzysztof , Gaweł Katarzyna , Botke Natalia , Zawada Iwona , Ławniczak Małgorzata , Białek Andrzej , Marlicz Wojciech
Published: October 2024

Background
Functional gastrointestinal disorders (FGIDs), now known as disorders of gut-brain interaction (DGBIs), such as Irritable Bowel Syndrome (IBS) and Functional Dyspepsia (FD), significantly impact global health, reducing quality of life and burdening healthcare systems. This study addresses the epidemiological gap in Poland, focusing on the West Pomeranian Voivodeship.
Methods
We conducted a cross-sectional study of 2070 Caucasian patients (58.2% female, mean age 57.5 ± 15.1 years) undergoing gastrointestinal endoscopic examinations at Pomeranian Medical University from 2021 to 2023. Data were collected using Rome IV diagnostic questionnaires and correlated with gastroduodenoscopy and colonoscopy findings. Exclusion criteria were age under 18, pregnancy, Crohn’s disease, ulcerative colitis, severe comorbidities, cancer, immunosuppressive therapy, ileostomy/colostomy, incomplete questionnaires, or lack of consent.
Results
Using Rome IV criteria, IBS was diagnosed in 436 participants (21.1%) and FD in 248 participants (12.0%). Post-endoscopic evaluation revised FD diagnoses to 184 individuals (8.9%). Females had a higher prevalence of IBS and FD (OR 1.64 and 1.61, respectively). No significant association was found between higher BMI and increased risk of IBS and FD. Hypertension and diabetes prevalence were 35.1% and 13.0%, respectively. Individuals with a history of COVID-19 had a higher risk of developing IBS (OR 1.47, P = 0.050).
Conclusions
Our study provides crucial epidemiological data on IBS and FD in Poland, emphasizing the importance of endoscopic evaluations. Our findings highlight the need for regional studies to understand local DGBI prevalence, aiding targeted healthcare strategies.
Comparison between operative management versus non-operative management in patients with blunt abdominal injury in National Trauma Registry of Iran
Authors: Mirzamohamadi Sara , HajiAbbasi Mohammad Navid , Ghorbani Somayeh , Salamati Payman , Zafarghandi Mohammadreza , Rahimi-Movaghar Vafa , Fakharian Esmaeil , Saeed-Banadaky Seyed Houssein , Hoseinpour Vahid , Isfahani Mehdi Nasr , Ghadiphasha Amir , Pourmasjedi Sobhan , Piri Seyed Mohammad , Naghdi Khatereh , Yazdi Seyed Amir Miratashi
Published: October 2024

Background
Trauma is one of the leading causes of death worldwide. Severe abdominal injuries cause one-fifth of injury mortality. Non-operative management (NOM) or operative management (OM) is a primary challenge in abdominal injuries. In this study, we aimed to compare NOM and OM outcomes in patients with blunt abdominal injuries in the National Trauma Registry of Iran (NTRI).
Method
This cross-sectional study was conducted with data from the NTRI from July 24th, 2016, to May 21st, 2023. All patients with an abdominal injury by road traffic crash (RTC), falls, hit or bodily fore, and assault with blunt objects were admitted to trauma registry member hospitals across the country according to the NTRI criteria included in this study.
Results
Liver, spleen, and kidney single-organ injuries managed non-operative more than operative 78 (75.7%), 101 (74.3%), and 34 (89.5%) vs. 25 (24.3%), 35 (25.7%), and 4 (10.5%) (P = 0.572, 0.845, and 0.019). Among multi-organ abdomen injuries, kidney injuries alongside spleen or liver injuries are managed non-operative more than operative. In the multivariate logistic regression model after adjustment, multi-organ abdomen injuries increased the chance of OM 3.57 times compared to NOM [OR:0.28, 95% CI: 0.171 to 0.489, p < 0.001]. Multiple logistic regression after adjustment revealed NOM did not increase mortality and decreased ICU admission compared to the OM.
Conclusion
We observed that NOM had no worse outcomes than OM. The liver, spleen, and kidney are mainly managed by non-operatives.
Effect of oral nintedanib vs placebo on epistaxis in hereditary hemorrhagic telangiectasia The EPICURE multicenter randomized double-blind trial
Authors: Hermann Ruben , Grobost Vincent , Le-Guillou Xavier , Lavigne Christian , Parrot Antoine , Rivière Sophie , Séguier Julie , Fargeton Anne-Emmanuelle , de-Montigny Aurélie , Huot Margaux , Decullier Evelyne , Roux Adeline , Gervaise Caroline , Cartier César , Dufour Xavier , Grall Margaux , Jegoux Frank , Laccourreye Laurent , Michel Justin , Saroul Nicolas , Wagner Isabelle , Kerjouan Mallorie , Dupuis-Girod Sophie
Published: October 2024

Epistaxis greatly affects patients with Hereditary Hemorrhagic Telangiectasia (HHT). Although few systemic treatment exist, nintedanib, is a good candidate thanks to its anti-angiogenic activity. Our main objective was to evaluate the efficacy of oral nintedanib on epistaxis duration in HHT patients with moderate to severe epistaxis. This multicenter phase 2 randomized, placebo-controlled, double-blind trial was conducted between June 2020 and February 2023. Inclusion criteria were being over 18 years old and having a confirmed HHT diagnosis with an epistaxis severity score greater than 4. Sixty patients were randomized to receive either nintedanib or placebo for 12 weeks with a 12 week follow-up. The primary endpoint was the proportion of patients achieving a reduction of at least 50% in mean monthly epistaxis duration comparing the 8 weeks before treatment to the last 8 weeks of treatment. Main secondary outcomes included monthly duration and frequency of epistaxis and hemoglobin levels. Of the 60 randomized patients, 56 completed the trial. Thirteen patients (43%) in the nintedanib group vs 8 (27%) in the placebo group met the primary endpoint (p = 0.28). We observed a significant decrease in median epistaxis (57% vs 27%, p = 0.013) and a significant increase median hemoglobin levels (+ 18 vs -1 g/L, p = 0.02) in the nintedanib vs the placebo group. Although we did not achieve our primary outcome, we observed a significant reduction in epistaxis duration and a significant increase in hemoglobin levels in patients treated with nintedanib. This supports the efficacy of nintedanib, and further studies are needed.
Effects of Loss-to-Follow-Up on Functional and Anatomic Outcomes in Patients with Neovascular Age-Related Macular Degeneration
Authors: Pandit Saagar A. , Obeid Anthony , Nair Archana A. , Patel Samir , Cohen Michael N. , Do Brian K. , Venkat Arthi , Choi Stephanie , Mathai Mariam , Modi Yasha S. , Dedania Vaidehi S.
Published: October 2024

Purpose: To study the effect of loss-to-follow-up (LTFU) in patients receiving anti-vascular endothelial growth factor (VEGF) injections for neovascular age-related macular degeneration (nAMD).
Patients and Methods: Retrospective, multi-center, cohort study of patients that received intravitreal bevacuzimab, ranibizumab, or aflibercept between January 2020 and March 2020 who were lost to follow-up.
Results: A total of 7114 eyes of 5727 patients met the study inclusion criteria. At the first return visit after LTFU, logMAR VA was 0.85 (Snellen 20/142) in the LTFU group compared to 0.67 (Snellen 20/94, p<0.001) in the control group. On the final study visit, VA in the LTFU group remained decreased at 0.86 (Snellen 20/145, p<0.001). For the LTFU group, mean CFT increased when comparing the visit before LTFU (280 µm) to the return visit (295 µm, p<0.001), but there was no difference at the final study visit (277 µm, p=0.42). Despite CFT returning back to GSD values by the final study visit for those LTFU, VA did not recover.
Conclusions: Patients with nAMD being treated with anti-VEGF who were lost to follow-up during the COVID-19 pandemic experienced irrecoverable loss in VA during the duration of the study, despite resumption of anti-VEGF therapy.
Exploring the Heterogeneity of HER2 gene status and Expression in Non-Positive Breast Cancer Patients: Insights from Immunohistochemistry and Fluorescence In Situ Hybridization
Authors: Zhong Jingmin , Gao Beibei , Wang Qingjie , He Jun , Luo Danjv , Zhang Chen , Fan Jun , Nie Xiu
Published: October 2024

Breast cancer became the most prevalent malignancy among women, and HER2 expression status is critical for treatment decisions. With the emergence of ADC drugs, HER2 low-expressing patients who previously did not respond well to traditional anti-HER2 therapies may now benefit. In this study, we evaluated HER2 expression in 349 HER2-non-positive breast cancer patients using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Our analysis revealed that HER2-low tumors exhibited fewer grade III tumors (39.74% and 55.65%, respectively, P = 0.005) and higher positivity for estrogen receptor (ER, 88.89% vs. 61.74%, P < 0.001) and progesterone receptor (PR, 84.62% vs. 57.39%, P < 0.001) compared to HER2-0 tumors. IHC interpretation varied widely, with antibodies showing only 67.3% and 65.3% agreement in HER2-0 and HER2-2 + groups (P < 0.001), respectively. Similarly, pathologists showed limited agreement, with 66.4% and 63.7% consistency in HER2-0 and HER2-2 + groups (P < 0.001). FISH analysis revealed significant differences in HER2 gene signals between HER2-0 and HER2-low tumors, but no clear cut-off value could be identified. Notably, HER2 gene red signal averages were mostly ≥ 2 and < 4, with HER2-0 tumors primarily ≤ 2.5, and HER2/CEP17 ratio mostly between 1 and 2, with HER2-0 tumors primarily ≤ 1.4. Despite distinct clinicopathological features, FISH remains inadequate for distinguishing HER2-low from HER2-0 expression. Future studies are needed to improve HER2 assessment in this challenging subset of patients.
HMOX1 Inhibits Ferroptosis in Non-Alcoholic Fatty Liver Disease
Authors: Yao Li , Zou Jun , Qiu Xin-ze , Liang Jing-rong , Qin Meng-bin , Zhang Jin-xiu , Peng Peng , Huang Jie-an
Published: October 2024

Background & Aims: This research seeks to elucidate the significance of ferroptosis-related genes in the diagnosis, prognosis, and treatment of non-alcoholic fatty liver disease (NAFLD).
Methods: Key genes pertinent to NAFLD were identified using the GEO database. The role of Heme oxygenase-1 (HMOX1) in NAFLD was validated via immunohistochemical analysis of hepatic tissues. Mice on a methionine-choline-deficient (MCD) diet were administered Hemin, followed by the collection of serum and liver samples for biochemical and histopathological examinations. HL7702 cells were transfected with a plasmid to elevate HMOX1 expression, then treated with oleic acid (OA) to induce lipid accumulation, and subsequently with erastin and AZD1480. A series of assays measured iron levels, reactive oxygen species, lipid peroxidation, and mitochondrial damage. Western blotting analysis was employed to elucidate the underlying molecular mechanisms.
Results: HMOX1 is crucial in the pathogenesis of NAFLD, evidenced by its decreased expression in patient liver tissues. Mice on an MCD diet exhibited significant hepatic steatosis, along with elevated levels of ALT, AST, TG, LDL, Fe2+, MDA, and ROS, and reduced levels of HMOX1 and GSH. Notably, Hemin effectively ameliorated NAFLD and prevented ferroptosis. Cellular analysis revealed activation of the JAK/STAT pathway in NAFLD. Upregulation of HMOX1 reduced OA-induced lipid peroxidation, inhibited ferroptosis, and suppressed the JAK/STAT pathway. Erastin negated the protective effects of HMOX1 overexpression. Moreover, the JAK/STAT pathway inhibitor AZD1480, which had the opposite effect with erastin, suppressed ferroptosis and ameliorated NAFLD.
Conclusions: This study elucidates that HMOX1 suppresses ferroptosis by inhibiting the JAK/STAT pathway in NAFLD.
Empathy in Practice: Comparing Physicians’ Self-assessment and Patient Perceptions Using the Jefferson Scales
Authors: Thomas Eliz , Shenod Shwetha , Madhu Bhavana
Published: October 2024

Background
Empathy in clinical practice is a pivotal tool for patient-centered care and improved outcomes. This study investigates the correlation between physicians’ self-assessed empathy and patient-perceived empathy, and explores how different factors influence these perceptions.
Methods
A hospital-based cross-sectional study was conducted with 40 physicians and 400 patients. Physicians were categorized according to their specialty, and empathy scores were assessed using the Jefferson Scale of Empathy. Physicians and their respective patients were given structured questionnaires to give their feedback.
Results
Of the 40 physicians, 47.5% were under 35 years, 42.5% were between 35–50 years, and 10% were over 50 years. Male physicians scored higher on empathy than females, but this difference had no statistical significance. Physicians aged 35–50 years rated themselves as being most empathetic, however, those over 50 years received the highest empathy scores (mean 32.05, p = 0.038) from the patients. Technical skill-oriented specialities (e.g., Dermatology, Surgery) had lower empathy scores (mean 30.8) compared to person-oriented specialties (mean 31.64).
Discussion
The study reveals an obvious discrepancy between self-assessment of physicians’ empathy score and patient perceptions. Older physicians received higher empathy scores, possibly due to their extensive experience and communication skills refined over the years. In contrast, younger physicians' self-ratings were higher, probably reflecting an idealized self-view. Specialties requiring more patient interaction scored higher in empathy, suggesting the realization and importance of communication skills in these departments.
Paracetamol, its metabolites and their transfer between maternal circulation and fetal brain in mono- and combination therapies
Authors: Huang Yifan , Qiu Fiona , Dziegielewska Katarzyna M , Habgood Mark D , Saunders Norman R
Published: October 2024

Background: Paracetamol is one of the most commonly used medications. Due to its availability and perceived safety, its use is recommended even during pregnancy and for neonates. It is often combined with other drugs required for various chronic treatments. However, potential effects of drug interactions on paracetamol brain entry, especially in early development, are mostly unknown.
Methods: Sprague Dawley rats at embryonic day E19, postnatal day P4, pregnant E19 dams and non-pregnant adult females were administered paracetamol (15 mg/kg) either as monotherapy or in combination with one of seven other drugs: cimetidine, digoxin, fluvoxamine, lamotrigine, lithium, olanzapine, valproate. Concentrations of parent paracetamol and its metabolites (paracetamol-glucuronide, paracetamol-glutathione and paracetamol-sulfate) in plasma, cerebrospinal fluid (CSF) and brain were measured by liquid chromatography and their entry into brain, CSF and transfer across the placenta were estimated.
Results: In monotherapy, the concentration of parent paracetamol in plasma, CSF and brain remained similar and at all ages its brain entry was unrestricted. In combination therapies, its entry into CSF increased following co-treatment with olanzapine, but decreased in co-treatment with lamotrigine. Placental transfer of parent paracetamol remained unchanged with drug co-treatments, however transfer of paracetamol-sulfate increased with lamotrigine co-administration. Acutely administered paracetamol was more extensively metabolized in adults compared to younger ages resulting in increased concentration of its metabolites with age.
Conclusions:
Developmental changes in the apparent brain and CSF entry of paracetamol appear to be determined more by its metabolism, rather than by cellular control of its transfer across brain and placental barriers.
Prediction of Preoperative Synchronous Distant Metastasis of Rectal Cancer Based on MRI Radiomics Model
Authors: Jiang Hao , Guo Wei , Lin Xue , Yu Zhuo , Qin Yudie , Sun Zhongqi , Hu Hongbo , Li Jinping , Zhang Linhan , Wu Qiong , Jiang Huijie
Published: October 2024

Purpose
The objective of this study was to develop and validate a new non-invasive artificial intelligence (AI) model based on preoperative magnetic resonance imaging (MRI) data to predict the presence of synchronous distant metastasis (SDM) in rectal cancer (RC).
Methods
169 eligible RC patients were enrolled, and T2WI and DWI sequence images were collected. The radiomics features were extracted through the PyRadiomics package of Python language, and a total of 1688 radiomics features were extracted, including first-order features, shape features, texture features, and Baud signs. One clinical model and three comprehensive models of clinical imaging were constructed. Five indexes including receiver operating characteristic (ROC), area under curve (AUC), accuracy, sensitivity, specificity, and 95% confidence interval (CI) were selected to evaluate the model. The clinical model using four independent risk factors (CEA, age, CA199, and T stage). Combining the clinical factors and imaging characteristics of different sequences, we established three clinically-imaging models: the DWI + clinical model, the T2W + clinical model, and the nomogram (radiomics + clinical) model.
Results
This nomogram model performed the best in predicting rectal cancer SDM. In the training set, the AUC, accuracy, sensitivity, specificity and 95%CI of the nomogram model were 0.93, 0.85, 0.85, 0.86, 0.89–0.96, respectively. In the test set, five indexes of the nomogram model were 0.94, 0.89, 0.88, 0.89, and 0.79 ~ 0.97, respectively. The correction plots were consistent between the predictions of the clinical radiomics model and the actual observed probabilities. Decision curve analysis showed that the nomogram model achieved the highest net benefit on the training set and the test set compared to the clinical model and the radiomics model.
Conclusion
Our predictive model is valuable for guiding and managing patients with rectal cancer SDM, providing options for improving patient treatment decisions and guiding personalized treatment regimens.
Correlation of hemoglobin, albumin, lymphocyte, and platelet (HALP) score with the probability of dyslipidemia in adults ≥ 20 years old: NHANES 2005- 2018 results
Authors: Li Ying , Huang Yuzhe , He Jinshen
Published: October 2024

Purpose
Insulin resistance, proinflammatory adipokines, oxidative stress, and inflammation are critical mechanisms of dyslipidemia. The hemoglobin albumin lymphocyte and platelet (HALP) score, a comprehensive measure, has remained utilized in this prognostic assessment of numerous diseases, yet it has been infrequently applied to dyslipidemia. This study uses a cross-sectional design to explore the relationship between the HALP score and dyslipidemia.
Methods
Data from individuals aged 20 and above were gathered from the National Health and Nutrition Examination Surveys (NHANES) database (2005–2018). Multivariable logistic regression models identified covariates and calculated odds ratios with 95% confidence intervals. Restricted cubic splines examined potential linear relationships, and stratified analyses based on HALP score and dyslipidemia were conducted. ROC curves assessed the model's predictive performance, including HALP groups, and nomograms were developed to estimate dyslipidemia risk.
Results
Regression models stratified by HALP score quartiles (Q1 < 37.31, 37.31 < Q2 ≤ 51.15, 51.15 < Q3 ≤ 69.68, 69.68 < Q4) revealed that participants in Q2, Q3, and Q4 had higher odds of dyslipidemia compared to Q1, confirmed by a test for trend. The model, including HALP, hypertension, chronic kidney disease, age, education, poverty-to-income ratio, smoking behavior, race, gender, and body mass index, showed the highest diagnostic accuracy for dyslipidemia. Subgroup analyses showed no robust interrelations.
Conclusion
This large-scale investigation demonstrates a curvilinear positive correlation bridging HALP score and dyslipidemia in U.S. adults.
The implication of TET1, miR-200 and miR-494 expression with tumor formation in colorectal cancer: through targeting WNT signaling
Authors: Tajali Raziye , Zali Neda , Noukabadi Fatemeh Naderi , Jalili Meysam , Valinezhad Morteza , ghasemian Farnaz , Cheraghpour Makan , savabkar Sanaz , Mojarad Ehsan Nazemalhosseini
Published: October 2024

Objective: Colorectal cancer (CRC) is a heterogeneous disease characterized by genetic and epigenetic alterations that contribute to tumor initiation and progression. Among these, dysregulation of the ten–eleven translocation (TET) DNA demethylases and the Wnt signaling pathway have been implicated in CRC pathogenesis. This study aimed to assess the expression level of selective miRNAs (miR-200 and miR-494), TET1 and Wnt1 in colorectal polyps, actual colorectal tumors, and normal adjacent tissues. We also evaluated the effect of 5-aza cytidine on the expression level of TET1 and wnt1 in the HT29 cell line.
Material and methods: TET1 and Wnt1 expression was assessed in 5-azacytidine-treated HT29 cells, a demethylating agent commonly used in cancer therapy. Additionally, we enrolled 114 individuals who underwent radical surgical colon resection, including 47 with cancerous tissues and 67 with polyps. We utilized qRT-PCR to measure mRNA levels of miR-200, miR-494, TET1 and Wnt1 in colorectal polyps, actual colorectal tumors, and normal adjacent tissues.
Results: TET1 expression was notably lower in both polyps and CRC tissue in comparison to adjacent normal tissue, with higher TET1 expression in tumors compared to polyps. Significant differences in miR-200 and miR-494 expression was observed in tumor samples compared to adjacent normal tissue. Furthermore, our in vitro experiments revealed that 5-azacytidine treatment upregulated TET1 and downregulated Wnt1 expression in CRC cell line, suggesting a potential therapeutic role for DNA demethylating agents in modulating TET1 and Wnt signaling in CRC development.
Conclusions: Overall, our findings provide further insight into the complex interplay between TET1, Wnt1 and selective miRNAs in CRC and their potential implications for diagnosis and treatment.
Exploratory profiling of metabolites in cerebrospinal fluid using a commercially available targeted metabolomics kit to discriminate leptomeningeal metastasis
Authors: Jang Soojin , Gwak Ho-Shin , Lee Kyue-Yim , Lee Jun Hwa , Kim Kyung-Hee , Kim Jong Heon , Park Jong Bae , Shin Sang Hoon , Yoo Heon , Dho Yun-Sik , Wang Kyu-Chang , Yoo Byong Chul
Published: October 2024

Background: Early diagnosis is needed for patients with leptomeningeal metastasis (LM); however, cerebrospinal fluid (CSF) cytology has low sensitivity, and imaging approaches are ineffective. We explored targeted CSF metabolic profiling to discriminate among LM and other conditions affecting the central nervous system (CNS).
Methods: We quantitatively measured amino acids, biogenic amines, hexose, acylcarnitines (AC), cholesteryl esters (CE), glycerides, phosphatidylcholines (PC), lysophosphatidylcholines (LPC), sphingomyelins (SM), and ceramides (Cer) in 117 CSF samples from healthy controls (HC, n=10) and patients with LM (LM, n=47), parenchymal brain tumor (PBT, n=45), or inflammatory disease (ID, n=13) with internal standards using the Absolute IDQ-p400 targeted mass spectrometry kit. Metabolites expressed in >90% of samples or showing a difference in proportional expression between groups ≥75% were used in logistic regression models.
Results: PC and SM had higher expression in LM than in PBT or HC, whereas LPC had lower expression in PBT than the other groups. Glycerides and Cer expression were higher in PBT and LM than in HC. Long-chain AC expression in PBT was lower than in LM or HC. A regression model including Ala, PC (42:7), PC (30:3), PC (37:0), and Tyr achieved complete discrimination (AUC=1.0) between LM and HC. In comparison of PBT and HC, twenty-six individual metabolites allowed complete discrimination between two groups, and between ID and HC fourty-six individual lipid metabolites allowed complete discrimination. Twenty-one individual metabolites (18 ACs and 3 PCs) allowed complete discrimination between LM and PBT.
Conclusions: Differentially expressed CSF metabolites, mostly lipids with unknown CNS and cell-type distributions, discriminate LM from other diseases. Identified discriminative profiles require future validation studies.
Introducing a novel homozygote TRAPPC10 mutation as a potential cause of developmental delay and intellectual disability in an Iranian family
Authors: Nozari Ahoura , Banitalebi Setareh , Babaahmadi Paria , Jalilian Narges , Sadeghi Taha , Hasani Mahdieh
Published: October 2024

Background
TRAPP complexes are crucial components for intracellular transport and cellular organization. Their role in vesicle trafficking, particularly through their involvement in the secretory pathway, make them more important in neurodevelopmental mechanisms. This study aims to identify a novel genetic variant, associated with developmental delay and intellectual disability by analyzing a consanguineous Iranian family.
Materials and Methods
Here, we performed whole-exome sequencing on an Iranian family, originating from a small population. The patient presented with severe developmental delay, microcephaly, and behavioral abnormalities. Through our analysis, we discovered a new biallelic variant on a previously introduced gene: TRAPPC10 (NM_003274.5): c.3222C > A; p.(Cys1074Ter) that is a potential cause for these specific clinical characteristics.
Results
Previous functional analysis suggest that the mutation causes premature termination of protein translation, likely leading to nonsense-mediated decay because of biallelic loss of functional TRAPPC10 protein which leads to severe developmental delay, microcephaly, and behavioral abnormalities such as aggression and autistic traits.
Conclusion
The aim of this research is to discover a novel variant in the TRAPPC10 gene that is responsible for a particular neurodevelopmental condition, dominantly characterized by developmental delay, intellectual disability, and microcephaly. These findings advance the comprehension of TRAPP-related diseases and emphasize the need for further exploration into the impact of TRAPPC10 on the development of the nervous system.
Deep Brain Stimulation of the Cortico-Basal Ganglia Network Enhances Cognitive Flexibility and Ameliorates Exploration Anomalies in a Primate Schizophrenia Model
Authors: Asch Nir , Rahamim Noa , Werner-Reiss Uri , Israel Zvi , Bergman Hagai
Published: October 2024

Learning thrives on cognitive flexibility and exploration. Subjects with schizophrenia have impaired cognitive flexibility and maladaptive exploration patterns. The basal ganglia-dorsolateral prefrontal cortex (BG-DLPFC) network plays a significant role in learning processes. However, how this network maintains cognitive flexibility and exploration patterns and what alters these patterns in schizophrenia remains elusive. Using a combination of extracellular recordings, pharmacological manipulations, macro-stimulation techniques, and adaptive reinforcement learning modeling, we show that in the nonhuman primate (NHP), the external segment of the globus pallidus (GPe, the central nucleus of the BG network) modulates cognitive flexibility and exploration patterns. We found that chronic, low-dose administration of N-methyl-D-aspartate receptor (NMDA-R) antagonist, phencyclidine (PCP), decreases directed exploration but increases random exploration, as seen in schizophrenia. However, low-frequency GPe macro-stimulation restores the balance of both exploration types. Our findings suggest that schizophrenia symptoms reflect abnormal BG-DLPFC balance, and GPe stimulation may be advantageous for these patients.
Evaluation of Image Quality of Temporal Maximum Intensity Projection and Average Intensity Projection of Adaptive 4D Spiral CT Scans: A Phantom Study
Authors: Horinouchi Hiroki , Sekitani Toshinori , Nishii Tatsuya , Negi Noriyuki , Sofue Keitaro , Fukuda Tetsuya , Takahashi Satoru
Published: October 2024

Adaptive four-dimensional (4D) spiral computed tomography (CT) scans facilitate the acquisition of volume perfusion data for organs or long-range vessels but optimizing image quality and reducing noise while minimizing radiation doses remains challenging. Thus, image-processing techniques such as temporal maximum intensity projection (MIP) and average intensity projection (AIP) are crucial in this context. This ex vivo study aimed to compare image noise, spatial resolution, and vessel diameter measurements between temporal MIP and AIP images with those of conventional CT images using phantoms. Three phantoms were scanned with equivalent radiation doses using single helical and adaptive 10-phase 4D spiral scans using a third-generation dual-source CT scanner. Temporal MIP and AIP images of 4D CT scans were generated by summing varying numbers of phases, incorporating automatic motion correction with non-rigid registration and a noise reduction algorithm. The CT values and image noise of the temporal MIP and AIP images were compared to conventional CT images. The task transfer function (TTF) was calculated using static phantoms. Vessel diameters of the phantoms for each image dataset were evaluated using motion phantoms. Temporal AIP images showed comparable CT values with those of the reference image, whereas the CT values of the temporal MIP images were significantly higher than those of the reference images (P < .01). The image noise of temporal AIP images with six or more phases was equal to or lower than that of the reference images. In contrast, temporal MIP images exhibited consistently high noise levels regardless of the number of summed phases. The TTF of temporal AIP images was comparable to that of the reference CT images. However, the TTF of temporal MIP images gradually decreased as the number of summed phases increased. No significant differences were observed in vessel diameter measurements among the three groups or with varying numbers of summed phases (P > .05). In conclusion, temporal MIP and AIP images from 4D CT can reduce noise and maintain measurement reliability in motion phantoms, achieving performance levels comparable to conventional CT images.
Genome wide association studies are enriched for interacting genes
Authors: Nguyen Peter T. , Coetzee Simon G. , Silacheva Irina , Hazelett Dennis J.
Published: October 2024

Background: With recent advances in single cell technology, high-throughput methods provide unique insight into disease mechanisms and more importantly, cell type origin. Here, we used multi-omics data to understand how genetic variants from genome-wide association studies influence development of disease. We show in principle how to use genetic algorithms with normal, matching pairs of single-nucleus RNA- and ATAC-seq, genome annotations, and protein-protein interaction data to describe the genes and cell types collectively and their contribution to increased risk.
Results: We used genetic algorithms to measure fitness of gene-cell set proposals against a series of objective functions that capture data and annotations. The highest information objective function captured protein-protein interactions. We observed significantly greater fitness scores and subgraph sizes in foreground vs.matching sets of control variants. Furthermore, our model reliably identified known targets and ligand-receptor pairs, consistent with prior studies.
Conclusions: Our findings suggested that application of genetic algorithms to association studies can generate a coherent cellular model of risk from a set of susceptibility variants. Further, we showed, using breast cancer as an example, that such variants have a greater number of physical interactions than expected due to chance.
Nonperturbative Nonlinear Transport in a Floquet-Weyl Semimetal
Authors: McIver James , Day Matthew , Kusyak Kateryna , Sturm Felix , Aranzadi Juan , Bretscher Hope , Fechner Michael , Matsuyama Toru , Michael Marios , Schulte Benedikt , Li Xinyu , Hagelstein Jesse , Hermann Dorothee , Kipp Gunda , Potts Alexander , Destefano Jonathan , Hu Chaowei , Huang Yunfei , Taniguchi Takashi , Watanabe Kenji , Meier Guido , Shin Dong bin , Rubio Angel , Chu Jiun-Haw , Kennes Dante , Sentef Michael
Published: October 2024

Periodic laser driving, known as Floquet engineering, is a powerful tool to manipulate the properties of quantum materials. Using circularly polarised light, artificial magnetic fields, called Berry curvature, can be created in the photon-dressed Floquet-Bloch states that form. This mechanism, when applied to 3D Dirac and Weyl systems, is predicted to lead to photon-dressed movement of Weyl nodes which should be detectable in the transport sector. The transport response of such a topological light-matter hybrid, however, remains experimentally unknown. Here, we report on the transport properties of the type-II Weyl semimetal Td-MoTe2 illuminated by a femtosecond pulse of circularly polarised light. Using an ultrafast optoelectronic device architecture, we observed injection currents and a helicity-dependent anomalous Hall effect whose scaling with laser field strongly deviate from the perturbative laws of nonlinear optics. We show using Floquet theory that this discovery corresponds to the formation of a magnetic Floquet-Weyl semimetal state. Numerical ab initio simulations support this interpretation, indicating that the light-induced motion of the Weyl nodes contributes substantially to the measured transport signals. This work demonstrates the ability to generate large effective magnetic fields (> 30T) with light, which can be used to manipulate the magnetic and topological properties of a range of quantum materials.
Residential fungal β-(1,3)-D-glucan exposure is associated with decreased pulmonary function in fibrotic pulmonary sarcoidosis.
Authors: Stapleton Emma M , Metwali Nervana , Shlossman Michael , Wendt Linder , Pezzulo Alejandro A , Hamzeh Nabeel Y , Comellas Alejandro P , Thorne Peter S , Gerke Alicia K
Published: October 2024

Background: Sarcoidosis is a multi-system disease frequently affecting the lungs. It is thought to be mediated by gene-environment interaction; for example, epidemiological data show organic aerosol exposure increases risk of pulmonary sarcoidosis.
Research Question: Does exposure to bioaerosol associate with worse lung disease in patients with pulmonary sarcoidosis?
Study Design and Methods: Using an observational, cohort study design, we measured residential exposure to fungal and bacterial cell wall material, β-(1,3)-D-glucan (BDG) and endotoxin, respectively, in healthy control subjects and those with pulmonary sarcoidosis. In the case cohort, we compared bioaerosol concentrations to pulmonary disease severity, assessed by pulmonary function testing, qualitative chest computed tomography (CT), and serum biomarkers. Log-transformed bioaerosol concentrations were compared to lung function and significance and correlation determined by Pearson correlation.
Results: Homes of subjects with sarcoidosis had higher BDG and endotoxin concentrations than control subjects. Patients with significant pulmonary fibrosis had greater disease severity (Wasfi severity score, visual analogue scale) and reduced pulmonary function compared to those without fibrosis (all P<0.01). Residential fungal BDG correlated with declining FVC, only in patients with fibrosis on CT imaging (P=0.02). Survey data revealed higher BDG concentrations were found in homes of cat-owners, and the number of houseplants owned correlated with declines in FVC and FEV1 (P=0.05 and 0.02, respectively). In patients without fibrosis, eight inflammatory markers correlated with BDG (6CKine/CCL21, IL-9, IL-17F, IL-21, IL-28A, I-309, MIP-1β, TARC), while in those with pulmonary fibrosis, BDG correlated with two inflammatory markers (Eotaxin-3, M-CSF), suggesting immune anergy to inhaled antigens in patients with fibrosis.
Interpretation: In patients with pulmonary fibrosis, disease severity was correlated with residential exposure to fungal cell wall material, but not gram-negative bacterial cell wall material. These patients may experience immune anergy to inhaled antigens.
An integrated model combined conventional radiomics and deep learning features to predict early recurrence of hepatocellular carcinoma eligible for curative ablation: a multicenter cohort study
Authors: Li Yonghai , Qian Guixiang , Zhu Yu , Lei Xuedi , Xu Ziling , Tang Lei , Bu Xiangyi , Wei Mingtong , Lu Jianlin , Jia Weidong
Published: October 2024

Aim This study aimed to develop and validate a model (DLRR) that incorporates deep learning radiomics and traditional radiomics features to predict ER following curative ablation for HCC.
Backround Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Ablation therapy is one of the first-line treatments for early HCC. Accurately predicting early recurrence (ER) is crucial for making precise treatment plans and improving prognosis.
Methods We retrospectively analysed the data of 288 eligible patients from three hospitals—one primary cohort (centre 1, n=222) and two external test cohorts (centre 2, n=32 and centre 3, n=34)—from April 2008 to March 2022. 3D ResNet-18 and PyRadiomics were applied to extract features from contrast-enhanced computed tomography (CECT) images. The three-step (ICC-LASSO-RFE) method was used for feature selection, and six machine learning methods were used to construct models. Performance was compared via the area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indices. Calibration and clinical applicability were assessed via calibration curves and decision curve analysis (DCA), respectively. Kaplan-Meier (K-M) curves were generated to stratify patients based on progression-free survival (PFS) and overall survival (OS).
Results The DLRR model had the best performance, with AUCs of 0.981, 0.910 and 0.851 in the training, internal validation, and external validation sets, respectively. NRI and IDI tests indicated that the DLRR model outperformed the DLR model (AUCs of 0.910 and 0.874; P < 0.05) and the Rad model (AUCs of 0.910 and 0.772; P < 0.05). Although the AUC of DLRR was slightly lower than that of the combined model (incorporating DLRR and clinico-radiological features), there was no significant difference (AUCs of 0.910 and 0.914; P > 0.05). Additionally, the calibration curve and DCA curve revealed that the DLRR model had good calibration ability and clinical applicability. The K-M curve indicated that the DLRR model provided risk stratification for progression-free survival (PFS) and overall survival (OS) in HCC patients.
Conclusion The DLRR model noninvasively and efficiently predicts ER after curative ablation in HCC patients, which helps to categorize the risk in patients to formulate precise diagnosis and treatment plans and management strategies for patients and to improve the prognosis.
Does hip bone morphology differ depending on the presence of Cam lesions in Borderline Developmental Dysplasia of the Hip?
Authors: Kuroda Yuichi , Kamenaga Tomoyuki , Araki Shotaro , Tsubosaka Masanori , Nakano Naoki , Matsumoto Tomoyuki , Kuroda Ryosuke , Hayashi Shinya
Published: October 2024

Objective. The purpose of this study was to divide patients with borderline developmental dysplasia of the hip (BDDH) into two groups according to the presence of Cam lesions, and compare radiographs related to bone morphology between them.
Materials and Methods.We retrospectively analyzed consecutive patients with BDDH who underwent hip arthroscopy (HA) or periacetabular osteotomy (PAO) at our institution between October 2013 and October 2019. The patients were classified into two groups according to the presence of Cam lesions. Radiographic measurements including lateral center-edge angle (LCEA), acetabular roof obliquity (ARO), cliff sign, femoral epiphyseal acetabular roof (FEAR) index, vertical center anterior angle (VCA), and Sourcil Index were compared between the two groups. The cutoff values were calculated using a receiver operating characteristic curve.
Results. Sixty-nine hips were analyzed in this study (Cam+: 34, Cam-: 35). The ARO and FEAR indexwere significantly higher in the Cam- group (P<0.001, P<0.001). The LCEA, VCA, and Sourcil Index was significantly lower in the Cam- group than that in the Cam+group (P<0.001, P<0.001, P<0.001). The cut-off values were 21.0° for LCEA, 15.1° for the ARO, 22.5° for the VCA angle, -2.2° for the FEAR index, and 49.5° for the Sourcil Index
Conclusion. Patients with BDDH exhibited significant differences in bone morphology depending on the presence of Cam lesions. Moreover, those without Cam lesions displayed similarities to patients with DDH. For such patients, performing HA alone risks poor clinical outcomes, and surgery to improve acetabular coverage, such as PAO, may be indicated.
Collective redox-shuttling properties of nanoalloys boost water electrolysis of nitrides
Authors: Duan Xinping , Zuo Peng , Li Na , Lu Jiawei , Zhang Jiayang , Wen Zhaojun , Fang Huihuang , Jiao Weizhou , Wang Ruixin , Lin Haiqiang
Published: October 2024

Interstitial transition metal catalysts (carbides, nitrides, and sulfides) represent the promising nonprecious metal bifunctional catalysts for water electrolysis. However, they still suffer from inferior activity and, particularly, stability for industrial applications. Leveraging template-free hydrothermal and reduction protocol, we report an unexpected collective effect between CoNi nanoalloy and molybdenum nitride (Mo2N) phase on Ni foam substrate (Mo2N@NiCo/NF). Distinct from the conventional promoting effect of the additives to parent metal motifs, the collective properties of local nanosized CoNi particles in Mo2N@NiCo/NF comprise differently-weighted geometric and electronic interactions, leading to remarkably enhanced hydrogen evolution reaction (HER) activity (18 and 67 mV at the current density of 10 and 100 mA cm−2, respectively) for Mo2N active sites in alkaline, relative to Pt/C@NF (87 mV at 100 mA cm−2). In-depth characterization, density functional theory (DFT) calculations, and electrocatalytic kinetics reveal that spatially located CoNi nanoalloy inside two-dimensional Mo2N nanoarrays serves as collective electron buffer, enabling the enhanced redox-shuttling properties and thus fulfilling the bifunctional catalytic activities for overall water and simulated seawater splitting with excellent durability (200 h at 50 or 100 mA cm−2). These results verify the importance of a collective properties strategy to design efficient bifunctional metal electrocatalysts for water electrolysis.
Examining the Impact of Human Brands on Sustainable Consumption Patterns: A Structural Equation Modeling Approach
Authors: Asiabar Mojtaba Ghorbani , Asiabar Morteza Ghorbani , Asiabar Alireza Ghorbani
Published: October 2024

This study investigates the influence of human brands on sustainable consumption patterns using a structural equation modeling approach. As environmental concerns grow and demand for sustainable products increases, understanding the factors that affect consumer behavior becomes crucial. This research aims to fill a gap in the literature by exploring the role of human brands in shaping attitudes and behaviors towards sustainable consumption. Data were collected through an online survey of 500 consumers across the country. Structural Equation Modeling (SEM) using AMOS software was employed to analyze the data. Results revealed that human brands have a significant positive impact on consumers' attitudes towards sustainable consumption (β = 0.42, p < 0.001) and intention to purchase sustainable products (β = 0.38, p < 0.001). Moreover, brand trust and brand identity were identified as mediating variables in this relationship. The study utilized a comprehensive model that incorporated various constructs, including human brand attributes, consumer perception, and sustainable consumption behaviors. The model demonstrated good fit indices (CFI = 0.95, TLI = 0.94, RMSEA = 0.058), supporting its validity. Additionally, a multi-group analysis revealed that the impact of human brands on sustainable consumption patterns was consistent across different demographic groups (Δχ2 = 7.23, df = 6, p > 0.05). This research offers new insights into the role of human brands in promoting sustainable consumption, with important implications for marketers and policymakers. The findings can contribute to the development of more effective strategies for encouraging sustainable consumer behaviors. Future studies could explore the influence of cultural and social factors on these relationships.
Effect of Substrate Temperature on the Structural and Optical Properties of CdO Thin Films Prepared Using Spray Pyrolysis
Authors: Aldabagh Araddah Abdulkhaleq , Zaker Thoalfiqar Ali , Uonis Mohammad Mahmood , Polus Tharaa Jirjees
Published: October 2024

Cadmium oxide films (CdO) have been deposited on glasse’s substrate at various temperature (150, 250 & 300 °C) using spray pyrolysis technique. Structural properties have been investigated by scanning electron microscope (SEM), X-ray spectroscopy, while optical properties were characterized (linear & nonlinear) using UV-Vis spectrometer and z-scan technique. SEM image shows clear effects of temperature increasing on thin film layer structure. Energy gap was changed from 2.2-2.05eV with substrate temperature. According to third order nonlinearity of CdO optical properties (which are very valuable for laser control device application and optical limiting), open and closed aperture Z-scan technique with (632.8 nm) He-Ne laser wavelength was used to measure the nonlinearity of optical parameters, which included refractive index variation and extinction coefficient.
Ransomware Detection Using Network Traffic Patterns: A Hybrid Approach with Isolation Forest and Gradient Boosting
Authors: Hagerty Scott , Huxley Dorian , Fiennes Adrian , Hartwell Lennox , Pembroke Malachi
Published: October 2024

The escalating prevalence of ransomware attacks, characterized by their complex and adaptive nature, poses significant threats to the integrity and availability of critical network infrastructures. As malicious actors continue to refine their techniques, traditional detection methods often prove insufficient, necessitating the exploration of more advanced and dynamic approaches to identify these threats promptly and accurately. In response to this pressing issue, a novel hybrid model has been developed, which synergistically combines the strengths of anomaly detection and classification algorithms to enhance the identification of ransomware activities. This approach is particularly significant due to its ability to effectively adapt to both known and unknown variants of ransomware, utilizing a comprehensive analysis of network traffic patterns. By integrating unsupervised techniques, such as Isolation Forest, with the classification prowess of Gradient Boosting, the model achieves a notable improvement in detection accuracy while simultaneously reducing the rate of false positives. This innovative framework not only streamlines the cybersecurity workflow but also bolsters the resilience of networks against increasingly sophisticated attacks, thus representing a crucial advancement in the ongoing battle against ransomware.