bluuebunny/crossref_metadata_2025_split huggingface dataset:
The expression of hypoxia inducible factor-1 alpha in diffuse large B-cell lymphoma (DLBCL) patients: a cross-sectional study in Indonesia
Authors: Pangarsa Eko Adhi , Rizky Daniel , Tandarto Kevin , Naibaho Ridho M. , Kurniawan Sigit P. , Istiadi Hermawan , Puspasari Dik , Santoso Antonius Gunawan , Setiawan Budi , Santosa Damai , Haryana Sofia Mubarika , Suharti Catharina 
Published: August 2023

Introduction:
Hypoxia fuels cancer growth by supporting blood vessel formation, suppressing immune response, and helping cancer cells adapt to harsh surroundings. This happens when cancer cells react to low oxygen levels by activating hypoxia inducible factor-1 alpha (HIF-1α). High levels of HIF-1α can indicate an aggressive form of cancer and resistance to treatment in diffuse large B-cell lymphoma (DLBCL) patients. This study aimed to identify which factors are linked to HIF-1α distribution using immunohistochemistry in DLBCL patients.

Method:
This study conducted at a hospital in Indonesia between 2020 and 2022 aimed to investigate factors associated with HIF-1α expression in DLBCL patients. Newly diagnosed DLBCL patients were categorized into two groups based on HIF-1α distribution (<40% and ≥40%). Various factors were analyzed between the two groups using statistical tests such as χ2, Mann–Whitney U, and Spearman correlation tests.

Results:
In this study, 40 participants diagnosed with DLBCL were divided into two groups based on their HIF-1α distribution. The group with HIF-1α distribution greater than or equal to 40% had a higher incidence of extranodal involvement, including primary extranodal disease, compared to the group with less than 40% distribution. This difference was statistically significant. The authors also found that haemoglobin level statistically significant (P=0.041) in this research. The Spearman test analysis showed negative correlation between haemoglobin (P = <0.05, r = −0.44) and positive correlation of soluble interleukin-2 receptor (sIL-2R) (P = <0.05, r = 0.5) with vascular endothelial growth factor (VEGF), as well as between tumour volume (P = <0.05, r = 0.37) with sIL-2R. Additionally, there was a positive correlation between VEGF and sIL-2R (P = <0.05, r= 0.5).

Conclusion:
Patients with higher HIF-1α expression (≥40%) had more extranodal involvement and primary extranodal disease in this study of 40 DLBCL patients. Haemoglobin level, sIL-2R, and VEGF were also identified as potential biomarkers.
The management of locally advanced, ulcerated breast cancer in a menopausal woman: a case report
Authors: Izzo Paolo , Izzo Luciano , Polistena Andrea , Sibio Simone , Codacci-Pisanelli Massimo , Crocetti Daniele , Gabriele Raimondo , De Intinis Claudia , Izzo Sara 
Published: August 2023

Introduction and importance:
This case report presents the clinical details of a 46-year-old postmenopausal woman who was diagnosed with a locally advanced, ulcerated, hormone receptor-positive, HER2-negative stage 2B lobular carcinoma of the breast. The complexity of the case necessitated a multidisciplinary, personalized approach.

Case presentation:
The patient, a postmenopausal woman, presented with locally advanced lobular carcinoma of the breast. The tumor was of significant size and exhibited ulceration. Given the hormone receptor-positive status of the tumor, a comprehensive treatment plan was formulated, taking into account the patient’s overall health and potential tolerance to treatment. Surgical removal of the tumor was performed, followed by adjuvant therapy with aromatase inhibitors.

Clinical discussion:
The complexity of this case highlights the importance of a personalized and patient-centered strategy in managing breast cancer. The patient’s menopausal status, tumor characteristics, and potential tolerance to treatment were crucial factors that influenced the treatment plan. The successful outcome of the treatment and the patient’s ability to tolerate the therapy underscores the significance of individualized treatment planning.

Conclusion:
This case report emphasizes the necessity for a comprehensive and patient-centered approach to managing complex cases of breast cancer. The findings support the development of personalized therapeutic strategies aimed at improving patient outcomes and quality of life. The successful treatment of the locally advanced, ulcerated lobular carcinoma of the breast in this postmenopausal patient further highlights the importance of considering individual factors and tailoring treatment plans accordingly.
High-Dose Naloxone Formulations Are Not as Essential as We Thought
Authors: Lemen Paige M. , Garrett Daniel P. , Thompson Erin , Aho Megan , Vasquez Christina , Park Ju Nyeong 
Published: August 2023

ABSTRACTNaloxone is a U.S. Food and Drug Administration (FDA) approved opioid antagonist for reversing opioid overdoses. Naloxone is available to the public, and can be administered through intramuscular (IM), intravenous (IV), and intranasal spray (IN) routes. Our literature review aimed to improve understanding regarding the adequacy of the regularly distributed two doses of low-dose IM or IN naloxone in effectively reversing fentanyl overdoses and whether high-dose naloxone formulations (HDNF) formulations are an optimal solution to this problem. Moreover, our initiative incorporated the perspectives and experiences of people who use drugs (PWUD), enabling a more practical and contextually-grounded analysis. We began by discussing the knowledge and perspectives of Tennessee Harm Reduction, a small peer-led harm reduction organization. A comprehensive literature review was then conducted to gather relevant scholarly works on the subject matter. The evidence indicates that, although higher doses of naloxone have been administered in both clinical and community settings, the vast majority of fentanyl overdoses can be successfully reversed using standard IM dosages with the exception of carfentanil overdoses and other more potent fentanyl analogs, which necessitate three or more doses for effective reversal. Multiple studies documented the risk of precipitated withdrawal using high doses of naloxone. Notably, the possibility of recurring overdose symptoms after resuscitation exists, contingent upon the half-life of the specific opioid. Considering these findings and the current community practice of distributing multiple doses, we recommend providing at least four standard doses of IN or IM naloxone to each potential bystander, and training them to continue administration until the recipient achieves stability, ensuring appropriate intervals between each dose. Based on the evidence, we do not recommend HDNF in the place of providing four doses of standard naloxone due to the higher cost, risk of precipitated withdrawal and limited evidence compared to standard IN and IM. All results must be taken into consideration with the inclusion of the lived experiences, individual requirements, and consent of PWUD as crucial factors. It is imperative to refrain from formulating decisions concerning PWUD in their absence, as their participation and voices should be integral to the decision-making process.
TLR8escapes X chromosome inactivation in human monocytes and CD4+T cells
Authors: Youness Ali , Cenac Claire , Faz-López Berenice , Grunenwald Solange , Barrat Franck J. , Chaumeil Julie , Mejía José Enrique , Guéry Jean-Charles 
Published: August 2023

AbstractHuman endosomal Toll-like receptors TLR7 and TLR8 recognize self and non-self RNA ligands, and are important mediators of innate immunity and autoimmune pathogenesis. TLR7 and TLR8 are encoded by the adjacent X-linked genes,TLR7andTLR8. We previously established thatTLR7evades X chromosome inactivation in female immune cells, and that mononuclear blood cells express more TLR7 protein in women than in men. Using RNA fluorescencein situhybridization, we now show thatTLR8likewise evades X chromosome inactivation in CD14+monocytes and CD4+T lymphocytes, and that cells harboringTLR7orTLR8transcript foci are more frequent in women than in men. In parallel, we foundTLR7andTLR8simultaneous transcription to be disproportionally frequent in female monocytes and T cells, and disproportionally scarce in the male cells, resulting in a 7-fold difference in frequency. These transcriptional biases were again observable when comparing the single X of XY males with the active X of female cells. Among (47,XXY) Klinefelter syndrome males, bothTLR7andTLR8escape X chromosome inactivation, and co-transcription frequencies on the active X of monocytes were intermediate overall between those for XY males and XX females, and encompassed both male- and female-like individual patterns. These findings indicate that theTLR7andTLR8genes form a co-regulated gene cluster, which we have called the X-linked Toll-like receptor locus, with different sex- and sexual karyotype-dependent modes of transcription. Interestingly, TLR8 protein expression was significantly higher in female mononuclear blood cells, including all monocyte subsets, than in the male cells. Thus, co-dependent transcription from the active X chromosome and escape from inactivation could both contribute to higher TLR8 protein abundance in female cells, which may have implications for the response to viruses and bacteria, and the risk of developing inflammatory and autoimmune diseases.HighlightsTLR8, likeTLR7, escapes X chromosome inactivation in immune cells from women and 47,XXY Klinefelter syndrome (KS) men.The frequency of cells double-positive forTLR7andTLR8primary transcripts is 7-fold higher in women than in men.TLR7andTLR8form a co-regulated gene cluster on the human X chromosome, with sex-specific, divergent transcriptional patterns observable in monocytes and CD4+T lymphocytes.Co-dependent transcription of theTLR7andTLR8genes on the active X was observed in women and KS men, contrasting with mutually exclusive transcription in euploid men.Blood mononuclear cells, including monocyte subsets, expressed higher levels of TLR8 protein in females than in males.
Markerless motion capture to assess upper extremity movements in individuals with dyskinetic cerebral palsy: an accuracy and validity study
Authors: Vanmechelen Inti , Van Wonterghem Ellen , Aerts Jean-Marie , Hallez Hans , Desloovere Kaat , Van de Walle Patricia , Buizer Annemieke I. , Monbaliu Elegast , Haberfehlner Helga 
Published: August 2023

AbstractAimTo evaluate clinical utility of markerless motion capture (MMC) during an reaching-sideways-task in individuals with dyskinetic cerebral palsy (DCP) by determining (1) accuracy of key points tracking in individuals with DCP and typically developing (TD) peers, (2) concurrent validity by correlating MMC towards 3D-motion analysis (3DMA) and (3) construct validity by assessing differences in MMC features between a DCP and TD group.MethodMMC key points were tracked from frontal videos and accuracy was assessed towards human labelling. Shoulder, elbow and wrist angles were calculated from MMC and 3DMA (as gold standard) and correlated. Additionally, execution time and variability features were calculated from key points. MMC features were compared between groups.ResultsFifty-one individuals (30 DCP;21 TD; age:5-24 years) participated. An accuracy of approximately 1.5 cm was reached for key point tracking. While significant correlations were found for wrist (ρ=0.810;p<0.001) and elbow angles (ρ=0.483;p<0.001), MMC shoulder angles were not correlated (ρ=0.247;p=0.102) to 3DMA. Wrist and elbow angles, execution time and variability features all differed between groups (Effect sizes 0.35-0.81;p<0.05).InterpretationVideos of a reaching-sideways-task processed by MMC to assess upper extremity movements in DCP showed promising accuracy and validity. The method is especially valuable to assess movement variability within DCP without expensive equipment.
Transfusion-transmitted infections among blood donors in South-East Italy: Contribution of blood transfusion centres for territory-based surveillance
Authors: Antonucci Francescopaolo , Faleo Antonietta , De Feo Lucia , Lombardi Luciano , Granato Tommaso 
Published: August 2023

ABSTRACTBackground and ObjectivesScreening for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV) infections and Syphilis in blood donors is important to evaluate both risk of transfusion-transmitted infections (TTIs) and their current prevalence in apparently healthy individuals. Apulia (South-East Italy) resulted to be one of the two Italian regions with the highest TTI cases.Screening tests results of blood donors were analysed, with the purpose to provide updated information on the epidemiology of TTIs.Materials and Methods117,454 donors referring to blood transfusion centres of the North Apulia between 2019-2022 were analysed; serum samples underwent analysis for TTIs by chemiluminescent-immunoassay and nucleic-acid-amplification tests.ResultsConfirmed reactivities were: 47 HBV (0.04%), 19 HCV (0.02%), 1 HIV (0.001%), and 42 Syphilis (0.04%), respectively. Of 47 HBV-infected donors, 28 were Hepatitis B surface Antigen (HBsAg) positive, including 8 with HBV-DNA positive, and 19 HBsAg negative but with detectable viraemia, identifying the presence of occult B infection (OBI). A higher number of positive cases resulted in the age group 51-65 (34 HBV, 12 HCV, 1 HIV and 25 Syphilis) and over 65 (4 HBV, 5 HCV, 0 HIV and 2 Syphilis) (p-value<0.05). Occasional donors showed higher frequency of TTIs compared to regular donors.ConclusionThe study shows consistent number of undiagnosed TTIs among blood donors, and the importance of transfusion centres for territory-based surveillance that can contribute to the detection of novel TTI cases among asymptomatic people, helping the diagnosis of submerged infectious diseases that are still a global threat.HIGHLIGHTSApulia is the second Italian region with the highest number of Transfusion-Transmitted Infections (TTI) among blood donors;In the period 2019-2022, HBV resulted to be the main TTI detected among blood donors, followed by Syphilis, HCV and HIV in North Apulia; the overall TTIs distribution resulted significantly higher among occasional donors than regular donors;Blood transfusion centres may represent important surveillance points for HBV, HCV, HIV and Syphilis and can contribute to the detection of novel TTI cases in apparently healthy individuals.
Sputum microbiome α-diversity is a key feature of the COPD frequent exacerbator phenotype
Authors: Pragman Alexa A. , Hodgson Shane W. , Wu Tianhua , Zank Allison , Reilly Cavan S. , Wendt Chris H. 
Published: August 2023

ABSTRACTBackgroundThe lung microbiome is an inflammatory stimulus whose role in chronic obstructive pulmonary disease (COPD) pathogenesis is incompletely understood. We hypothesized that the frequent exacerbator phenotype is associated with decreased α-diversity and increased lung inflammation. Our objective was to assess correlations between the frequent exacerbator phenotype, the microbiome, and inflammation longitudinally during exacerbation-free periods.MethodsWe conducted a case-control longitudinal observational study of the frequent exacerbator phenotype and characteristics of the airway microbiome. Eighty-one subjects (41 frequent and 40 infrequent exacerbators) provided nasal, oral, and sputum microbiome samples at two visits over 2-4 months. Exacerbation phenotype, relevant clinical factors, and sputum cytokine values were associated with microbiome findings.ResultsThe frequent exacerbator phenotype was associated with lower sputum microbiome α-diversity (p=0.0031). This decrease in α-diversity among frequent exacerbators was enhanced when the sputum bacterial culture was positive (p<0.001). Older age was associated with decreased sputum microbiome α-diversity (p=0.0030). Between-visit β-diversity was increased among frequent exacerbators and those who experienced a COPD exacerbation between visits (p=0.025, p=0.014). Sputum cytokine values did not differ based on exacerbation phenotype or other clinical characteristics. IL-17A was negatively associated with α-diversity, while IL-6 and IL-8 were positively associated with α-diversity (p=0.012, p=0.012, p=0.0496). IL-22, IL-17A, and IL-5 levels were positively associated withMoraxellaabundance (p=0.027, p=0.0014, p=0.0020).ConclusionsEven during exacerbation-free intervals, the COPD frequent exacerbator phenotype is associated with decreased sputum microbiome α-diversity and increased β-diversity. Decreased sputum microbiome α-diversity andMoraxellaabundance are associated with lung inflammation.
Association between physical multimorbidity and common mental health disorders in rural and urban Malawian settings: preliminary findings from Healthy Lives Malawi long-term conditions survey
Authors: Nkoka Owen , Munthali-Mkandawire Shekinah , Mwandira Kondwani , Nindi Providence , Dube Albert , Nyanjagha Innocent , Mainjeni Angella , Malava Jullita , Amoah Abena S , McLean Estelle , Stewart Robert , Crampin Amelia C , Price Alison J 
Published: August 2023

AbstractIn low-income Africa, the epidemiology of physical multimorbidity and associated mental health conditions is not well described. We investigated the multimorbidity burden, disease combinations, and relationship between physical multimorbidity and common mental health disorders in rural and urban Malawi using early data from 9,849 adults recruited to an on-going large cross-sectional study on long-term conditions, initiated in 2021. Multimorbidity was defined as having two or more measured (diabetes, hypertension) or self-reported (diabetes, hypertension, disability, chronic pain, HIV, asthma, stroke, heart disease, and epilepsy). Depression and anxiety symptoms were scored using the 9-item Patient Health Questionnaire and 7-item General Anxiety Disorder scale and defined by the total score (range 0–27 and 0–21, respectively). We determined age-standardized multimorbidity prevalence and condition combinations. Additionally, we used multiple linear regression models to examine the association between physical multimorbidity and depression and anxiety symptom scores. Of participants, 81% were rural dwelling, 56% were female, and the median age was 30 years (IQR 21–43). The age-standardized urban and rural prevalence of multimorbidity was 14.1% (95% CI, 12.5–15.8%) and 12.2% (95% CI, 11.6–12.9%), respectively. In adults with two conditions, hypertension, and disability (18%) co-occurred most frequently, and in those with three conditions, hypertension, disability, and chronic pain (23%) were the most common combination. Compared to adults without physical conditions, having one (B-Coefficient (B) 0.78; 95% C1 0.63–0.95%), two-(B1.36; 95% CI 1.14–1.58%), and three- or more-physical conditions (B2.23; 95% CI 1.87–2.59%) were associated with increasing depression score,p-trend <0.001. A comparable ‘dose-response’ relationship was observed between physical multimorbidity and anxiety symptom scores. While the direction of observed associations cannot be determined with these cross-sectional data, our findings highlight the burden of multimorbidity and need for integrating mental and physical health service delivery in Malawi.
ChatGPT-CARE: a Superior Decision Support Tool Enhancing ChatGPT with Clinical Practice Guidelines
Authors: Wang Yanshan , Visweswaran Shyam , Kapoor Sumit , Kooragayalu Shravan , Wu Xizhi 
Published: August 2023

AbstractChatGPT has gained remarkable traction since its inception in November 2022. However, it faces limitations in generating inaccurate responses, ignoring existing guidelines, and lacking reasoning when applied in clinical settings. This study introduces ChatGPT-CARE, a tool that integrates clinical practice guidelines with ChatGPT, focusing on COVID-19 outpatient treatment decisions. By employing in-context learning and chain-of-thought prompting techniques, ChatGPT-CARE enhances original ChatGPT’s clinical decision support and reasoning capabilities. We created three categories of various descriptions of patients seeking COVID-19 treatment to evaluate the proposed tool, and asked two physicians specialized in pulmonary disease and critical care to assess the responses for accuracy, hallucination, and clarity. The results indicate that ChatGPT-CARE offers increased accuracy and clarity, with moderate hallucination, compared to the original ChatGPT. The proposal ChatGPT-CARE could be a viable AI-driven clinical decision support tool superior to ChatGPT, with potential applications beyond COVID-19 treatment decision support.
The Influence of Multivalent Charge and PEGylation on Shape Transitions in Fluid Lipid Assemblies: From Vesicles to Discs, Rods, and Spheres
Authors: Steffes Victoria M. , Zhang Zhening , Ewert Kai K. , Safinya Cyrus R. 
Published: August 2023

AbstractLipids, and cationic lipids in particular, are of interest as delivery vectors for hydrophobic drugs such as the cancer therapeutic paclitaxel, and the structures of lipid assemblies affect their efficacy. We investigated the effect of incorporating the multivalent cationic lipid MVL5 (+5e) and poly(ethylene glycol)-lipids (PEG-lipids), alone and in combination, on the structure of fluid-phase lipid assemblies of the charge-neutral lipid 1,2-dioleoyl-sn-glycero-phosphocholine (DOPC). This allowed us to elucidate lipid–liposome structure correlations in sonicated formulations with high charge density, which are not accessible with univalent lipids such as the well-studied DOTAP (+1e). Cryogenic TEM allowed us to determine the structure of the lipid assemblies, revealing diverse combinations of vesicles and disc-shaped, worm-like, and spherical micelles. Remarkably, MVL5 forms an essentially pure phase of disc micelles at 50 mol% MVL5. At higher (75 mol%) content of MVL5, short and intermediate-length worm-like micellar rods were observed and, in ternary mixtures with PEG-lipid, longer and highly flexible worm-like micelles formed. Independent of their length, the worm-like micelles coexisted with spherical micelles. In stark contrast, DOTAP forms mixtures of vesicles, disc micelles and spherical micelles at all studied compositions, even when combined with PEG-lipids. The observed similarities and differences in the effects of charge (multivalent versus univalent) and high curvature (multivalent charge versus PEG-lipid) on assembly structure provide insights into parameters that control the size of fluid lipid nanodiscs, relevant for future applications.