bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of cannabis use, perception of harm, and perceived impact of legislative change in an online sample of young adults from Lebanon: insight on recreational users versus dual motive users
Authors: Ghandour Lilian , Slim Andre , Abbas Nada , El-Khoury Joseph 
Published: February 2024

Abstract
Background
Lebanon remains as one of the major sources of cannabis worldwide. In 2020, its government passed a legislation enabling the cultivation of local medicinal cannabis. This first study following the legislative change examines the overlapping use of cannabis for recreational/medicinal purposes and characteristics of the distinct cannabis user types.

Methods
A total of 1230 young adults (18–24 years) filled an anonymous online survey in early 2020.

Results
Young adults in the sample were distributed as follows: 33% 18–20 years; 60% males; 94% Lebanese; 75% students; and 89% living with family. The older young adults (21–24), males, those employed, living with non-family members, and who perceived themselves as being a little/lot richer than most were statistically significantly more present in the cannabis user subtypes (recreational only or recreational/medicinal) than non-cannabis users. When dual recreational/medicinal users are compared to recreational users only, the latter seemed to have a more conservative profile of behaviours, attitudes, and perceptions and acts of harm. The prevalence ratio comparing the prevalence of users supporting consuming cannabis “once or twice” in dual motive users vs. recreational users only was 1.13 for “once or twice”, 1.25 for “occasionally”, 1.64 for “regularly”, and 2.4 for “daily”. Any other illicit drug use was reported by 1% of the non-cannabis users, 36% of the recreational users only, and 58% of the recreational/medicinal users (p-value < 0.01). Similarly, any prescription drug use was reported by 3% of the non-cannabis users, 16% of the recreational users only, and 28% of both recreational/medicinal users (p-value < 0.01).

Conclusion
The interface between recreational and medicinal cannabis use is complex. Dual motive users may warrant special attention as a subpopulation of cannabis users. This is relevant to contexts experiencing medicinal cannabis legislation changes, such as Lebanon, as policymakers and implementers should be sensitized to the emerging evidence for more data-informed policy changes.
Glycosaminoglycan modifications of betaglycan regulate ectodomain shedding to fine-tune TGF-β signaling responses in ovarian cancer
Authors: Choi Alex S. , Jenkins-Lane Laura M. , Barton Wade , Kumari Asha , Lancaster Carly , Raulerson Calen , Ji Hao , Altomare Diego , Starr Mark D. , Whitaker Regina , Phaeton Rebecca , Arend Rebecca , Shtutman Michael , Nixon Andrew B. , Hempel Nadine , Lee Nam Y. , Mythreye Karthikeyan 
Published: February 2024

AbstractIn pathologies including cancer, aberrant Transforming Growth Factor-β (TGF-β) signaling exerts profound tumor intrinsic and extrinsic consequences. Intense clinical endeavors are underway to target this pathway. Central to the success of these interventions is pinpointing factors that decisively modulate the TGF-β responses. Betaglycan/type III TGF-β receptor (TβRIII), is an established co-receptor for the TGF-β superfamily known to bind directly to TGF-βs 1–3 and inhibin A/B. Betaglycan can be membrane-bound and also undergo ectodomain cleavage to produce soluble-betaglycan that can sequester its ligands. Its extracellular domain undergoes heparan sulfate and chondroitin sulfate glycosaminoglycan modifications, transforming betaglycan into a proteoglycan. We report the unexpected discovery that the heparan sulfate glycosaminoglycan chains on betaglycan are critical for the ectodomain shedding. In the absence of such glycosaminoglycan chains betaglycan is not shed, a feature indispensable for the ability of betaglycan to suppress TGF-β signaling and the cells' responses to exogenous TGF-β ligands. Using unbiased transcriptomics, we identified TIMP3 as a key inhibitor of betaglycan shedding thereby influencing TGF-β signaling. Our results bear significant clinical relevance as modified betaglycan is present in the ascites of patients with ovarian cancer and can serve as a marker for predicting patient outcomes and TGF-β signaling responses. These studies are the first to demonstrate a unique reliance on the glycosaminoglycan chains of betaglycan for shedding and influence on TGF-β signaling responses. Dysregulated shedding of TGF-β receptors plays a vital role in determining the response and availability of TGF-βs’, which is crucial for prognostic predictions and understanding of TGF-β signaling dynamics.
Targeting cancer-derived extracellular vesicles by combining CD147 inhibition with tissue factor pathway inhibitor for the management of urothelial cancer cells
Authors: Boddu Vijay Kumar , Zamzow Piet , Kramer Mario Wolfgang , Merseburger Axel S. , Gorantla Sivahari Prasad , Klinger Matthias , Cramer Lena , Sauer Thorben , Gemoll Timo , von Bubnoff Nikolas , Gieseler Frank , Darabi Masoud 
Published: February 2024

Abstract
Background
Extracellular vesicles (EVs), including microvesicles, hold promise for the management of bladder urothelial carcinoma (BLCA), particularly because of their utility in identifying therapeutic targets and their diagnostic potential using easily accessible urine samples. Among the transmembrane glycoproteins highly enriched in cancer-derived EVs, tissue factor (TF) and CD147 have been implicated in promoting tumor progression. In this in vitro study, we explored a novel approach to impede cancer cell migration and metastasis by simultaneously targeting these molecules on urothelial cancer-derived EVs.

Methods
Cell culture supernatants from invasive and non-invasive bladder cancer cell lines and urine samples from patients with BLCA were collected. Large, microvesicle-like EVs were isolated using sequential centrifugation and characterized by electron microscopy, nanoparticle tracking analysis, and flow cytometry. The impact of urinary or cell supernatant-derived EVs on cellular phenotypes was evaluated using cell-based assays following combined treatment with a specific CD147 inhibitor alone or in combination with a tissue factor pathway inhibitor (TFPI), an endogenous anticoagulant protein that can be released by low-molecular-weight heparins.

Results
We observed that EVs obtained from the urine samples of patients with muscle-invasive BLCA and from the aggressive bladder cancer cell line J82 exhibited higher TF activity and CD147 expression levels than did their non-invasive counterparts. The shedding of GFP-tagged CD147 into isolated vesicles demonstrated that the vesicles originated from plasma cell membranes. EVs originating from invasive cancer cells were found to trigger migration, secretion of matrix metalloproteinases (MMPs), and invasion. The same induction of MMP activity was replicated using EVs obtained from urine samples of patients with invasive BLCA. EVs derived from cancer cell clones overexpressing TF and CD147 were produced in higher quantities and exhibited a higher invasive potential than those from control cancer cells. TFPI interfered with the effect when used in conjunction with the CD147 inhibitor, further suppressing homotypic EV-induced migration, MMP production, and invasion.

Conclusions
Our findings suggest that combining a CD147 inhibitor with low molecular weight heparins to induce TFPI release may be a promising therapeutic approach for urothelial cancer management. This combination can potentially suppress the tumor-promoting actions of cancer-derived microvesicle-like EVs, including collective matrix invasion.

Graphical Abstract
Autophagy inhibition improves the targeted radionuclide therapy efficacy of 131I-FAP-2286 in pancreatic cancer xenografts
Authors: Liu Xingyu , Li Danni , Ma Tianbao , Luo Xiu , Peng Ye , Wang Tao , Zuo Changjing , Cai Jianming 
Published: February 2024

Abstract
Purposes
Radiotherapy can induce tumor cell autophagy, which might impair the antitumoral effect. This study aims to investigate the effect of autophagy inhibition on the targeted radionuclide therapy (TRT) efficacy of 131I-FAP-2286 in pancreatic cancer.

Methods
Human pancreatic cancer PANC-1 cells were exposed to 131I-FAP-2286 radiotherapy alone or with the autophagy inhibitor 3-MA. The autophagy level and proliferative activity of PANC-1 cells were analyzed. The pancreatic cancer xenograft-bearing nude mice were established by the co-injection of PANC-1 cells and pancreatic cancer-associated fibroblasts (CAFs), and then were randomly divided into four groups and treated with saline (control group), 3-MA, 131I-FAP-2286 and 131I-FAP-2286 + 3-MA, respectively. SPECT/CT imaging was performed to evaluate the bio-distribution of 131I-FAP-2286 in pancreatic cancer-bearing mice. The therapeutic effect of tumor was evaluated by 18F-FDG PET/CT imaging, tumor volume measurements, and the hematoxylin and eosin (H&E) staining, and immunohistochemical staining assay of tumor tissues.

Results
131I-FAP-2286 inhibited proliferation and increased the autophagy level of PANC-1 cells in a dose-dependent manner. 3-MA promoted 131I-FAP-2286-induced apoptosis of PANC-1 cells via suppressing autophagy. SPECT/CT imaging of pancreatic cancer xenograft-bearing nude mice showed that 131I-FAP-2286 can target the tumor effectively. According to 18F-FDG PET/CT imaging, the tumor growth curves and immunohistochemical analysis, 131I-FAP-2286 TRT was capable of suppressing the growth of pancreatic tumor accompanying with autophagy induction, but the addition of 3-MA enabled 131I-FAP-2286 to achieve a better therapeutic effect along with the autophagy inhibition. In addition, 3-MA alone did not inhibit tumor growth.

Conclusions
131I-FAP-2286 exposure induces the protective autophagy of pancreatic cancer cells, and the application of autophagy inhibitor is capable of enhancing the TRT therapeutic effect.
Low rate of severe-end-stage kidney disease after SABR for localised primary kidney cancer
Authors: Ali Muhammad , Koo Kendrick , Chang David , Chan Phil , Oon Sheng F. , Moon Daniel , Murphy Declan G. , Eapen Renu , Goad Jeremy , Lawrentschuk Nathan , Azad Arun A. , Chander Sarat , Shaw Mark , Hardcastle Nicholas , Siva Shankar 
Published: February 2024

Abstract
Background
Stereotactic ablative body radiotherapy (SABR) is an emerging treatment for patients with primary renal cell carcinoma (RCC). However, its impact on renal function is unclear. This study aimed to evaluate incidence and clinical factors predictive of severe to end-stage chronic kidney disease (CKD) after SABR for RCC.

Methods and materials
This was a Single institutional retrospective analysis of patients with diagnosed primary RCC receiving SABR between 2012–2020. Adult patients with no metastatic disease, baseline estimated glomerular filtration rate (eGFR) of ≥ 30 ml/min/1.73 m2, and at least one post-SABR eGFR at six months or later were included in this analysis. Patients with upper tract urothelial carcinoma were excluded. Primary outcome was freedom from severe to end-stage CKD, determined using the Kaplan–Meier estimator. The impact of baseline CKD, age, hypertension, diabetes, tumor size and fractionation schedule were assessed by Cox proportional hazard models.

Results
Seventy-eight consecutive patients were included, with median age of 77.8 years (IQR 70–83), tumor size of 4.5 cm (IQR 3.9–5.8) and follow-up of 42.2 months (IQR 23–60). Baseline median eGFR was 58 mls/min; 55% (n = 43) of patients had baseline CKD stage 3 and the remainder stage 1–2. By last follow-up, 1/35 (2.8%) of baseline CKD 1–2, 7/27 (25.9%) CKD 3a and 11/16 (68.8%) CKD 3b had developed CKD stage 4–5. The estimated probability of freedom from CKD stage 4–5 at 1 and 5 years was 89.6% (CI 83.0–97.6) and 65% (CI 51.4–81.7) respectively. On univariable analysis, worse baseline CKD (p < 0.0001) and multi-fraction SABR (p = 0.005) were predictive for development of stage 4–5 CKD though only the former remained significant in multivariable model.

Conclusion
In this elderly cohort with pre-existing renal dysfunction, SABR achieved satisfactory nephron sparing with acceptable rates of severe to end-stage CKD. It can be an attractive option in patients who are medically inoperable.
Characterizing the detection of inactivated Mycoplasma hyopneumoniae DNA in the respiratory tract of pigs
Authors: Canturri Albert , Pieters Maria 
Published: February 2024

AbstractA positive Mycoplasma hyopneumoniae PCR result in a clinical specimen may eventually represent the mere detection of non-viable bacteria, complicating the diagnostic interpretation. Thus, the objective of this study was to evaluate the PCR detection of non-viable M. hyopneumoniae and its residual cell-free DNA in live pigs. Pigs were inoculated with either active or inactivated M. hyopneumoniae and were sampled for up to 14 days. Mycoplasma hyopneumoniae was not detected by PCR at any timepoint in pigs inoculated with the inactivated bacterium, suggesting that in healthy pigs, the non-viable M. hyopneumoniae DNA was rapidly sensed and cleared.
Anti-inflammatory effects of TP1 in LPS-induced Raw264.7 macrophages
Authors: Kim Minji , An Jangeun , Shin Seong-Ah , Moon Sun Young , Kim Moonsu , Choi Seyeon , Kim Huiji , Phi Kim-Hoa , Lee Jun Hyuck , Youn Ui Joung , Park Hyun Ho , Lee Chang Sup 
Published: February 2024

AbstractInflammation is an essential defense mechanism in health; however, excessive inflammation contributes to the pathophysiology of several chronic diseases. Although anti-inflammatory drugs are essential for controlling inflammation, they have several side effects. Recent findings suggest that naturally derived compounds possess physiological activities, including anti-inflammatory, antifungal, antiviral, anticancer, and immunomodulatory activities. Therefore, this study aimed to investigate the anti-inflammatory effects and molecular mechanisms of 2,5,6-trimethoxy-p-terphenyl (TP1), extracted from the Antarctic lichen Stereocaulon alpinum, using in vitro models. TP1 treatment decreased the production of nitric oxide (NO) and reactive oxygen species (ROS) in LPS-stimulated Raw264.7 macrophages. Additionally, TP1 treatment significantly decreased the mRNA levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) and the mRNA and protein levels of the pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2). Moreover, TP1 suppressed lipopolysaccharide-induced phosphorylation of the NF-κB and MAPK signaling pathways in Raw264.7 macrophages. Conclusively, these results suggest that TP1 ameliorates inflammation by suppressing the expression of pro-inflammatory cytokines, making it a potential anti-inflammatory drug for the treatment of severe inflammatory diseases.
Utilization of early postnatal care services and associated factors among mothers who gave birth in the last 12 months in South Gondar Zone District, Amhara Regional State, Ethiopia
Authors: Yimer Tigist Seid , Ferede Wassie Yazie , Sisay Fillorence Ayalew 
Published: February 2024

AbstractIntroductionPostnatal care is care that is provided to mothers and newborn baby after delivery. The care given after childbirth is the most critical time because most maternal and neonatal mortality occurs during this period. Utilization of this service is low in Ethiopia, and no evidence exists to describe the status of early postnatal care service utilization among women in the study area.ObjectiveThis study aimed to assess the utilization of early postnatal care services and associated factors among mothers who gave birth in the last 12 months in the South Gondar Zone District, Amhara Region, Ethiopia, in 2021.MethodThis study was conducted in South Gondar Zone Districts from October 1 to 30, 2021. A total of 761 participants were included in this study using a simple random sampling method. The study participants were mothers who gave birth in the last 12 months. The data were collected via interview-guided semistructured questionnaires. The collected data were coded and entered into EPI Info version 7.2 and exported into SPSS version 23 for analysis. Both binary and multivariate logistic regression analyses were applied to identify factors affecting the outcome variables. The results of the final model are presented as the adjusted odds ratio (AOR) and 95% confidence interval (CI). A P value less than 0.05 was considered to indicate statistical significance.ResultsIn this study, 761 mothers participated, for a response rate of 100%. The overall prevalence of early utilization of postnatal care services was 20.6%. Mothers who live in urban areas were five times more likely to have early visits than those living in rural areas with adjusted odds ratio [AOR (95% CI) = 5.2 (3.19, 8.54)], a mothers who had a history of more than four parity had more likely to visit than the others at [AOR (95% CI) = 2.25 (1.18, 4.29)], mothers who had a history of pregnancy had two times more likely to visit than the other [AOR (95% CI) = 2.06 (1.05, 4.05)], and mothers who had delivered by instrumental vaginal delivery or cesarean section delivery and those mothers who had mass media exposure were two and five times more likely to visit, respectively [AOR (95% CI) = 2.62 (1.40, 4.91)] and [AOR (95% CI) = 5.18 (2.55, 10.52)].Conclusion and recommendationCompared with those of other studies, the overall prevalence of early utilization of postnatal care services was low. Improving mothers’ knowledge of early postnatal care visits is very important for enhancing quality of life and minimizing neonatal and maternal morbidity and mortality.
Development and Internal Validation of a Prediction Model for Nasopharyngeal Carcinoma: Using BMI and Inflammatory Response for Deciding Sequence of Chemotherapy
Authors: Setakornnukul Jiraporn , Petsuksiri Janjira , Chaysiri Panid , Danchaivijitr Pongwut , Ngamphaiboon Nuttapong , Thephamongkhol Kullathorn 
Published: February 2024

PURPOSE Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CRT-AC) and induction chemotherapy followed by concurrent chemoradiotherapy (IC-CRT) are among the best treatments in nasopharyngeal carcinoma (NPC). This study aimed to develop a model for deciding the sequence of chemotherapy in NPC. METHODS Data were separated into two cohorts. The CRT-AC cohort had 295 patients, while the IC-CRT cohort had 112. The predictors were standard factors with BMI and neutrophil-lymphocyte ratio (NLR) to predict overall survival (OS). A flexible parametric survival model was used. RESULTS A total of 132 (44.7%) and 72 patients (64.3%) died in the CRT-AC and IC-CRT cohorts, respectively. The predictors in the final models were age, sex, T, N, NLR, and BMI. The models of OS for CRT-AC and IC-CRT had concordance indices of 0.689 and 0.712, respectively, with good calibration curves. When changing the burden of disease along with NLR and BMI, we found that CRT-AC was not significantly different OS from IC-CRT when low NLR (<3) and high burden of disease (T3N3). By contrast, CRT-AC was remarkably more effective when there were high levels of NLR (≥3) and BMI (≥25) with any burden of disease (anyT anyN). CONCLUSION With additional BMI and NLR in model, it could be easier to decide between CRT-AC and IC-CRT in countries with limited health care resources.
Real-World Cervical Cancer Screening Uptake and Predictors of Visual Inspection With Acetic Acid Positivity Among Women Living With HIV in Care Programs in Western Kenya
Authors: Mungo Chemtai , Orang'o Omenge , Ofner Susan , Musick Beverly , Yiannoutsos Constantin , Cohen Craig R. , Brown Darron , Wools-Kaloustian Kara , Semeere Aggrey 
Published: February 2024

PURPOSE To achieve the WHO cervical cancer elimination targets, countries globally must achieve 70% cervical cancer screening (CCS) coverage. We evaluated CCS uptake and predictors of screening positive at two public HIV care programs in western Kenya. METHODS From October 2007 to February 2019, data from the Family AIDS Care and Education Services (FACES) and Academic Model Providing Access to Healthcare (AMPATH) programs in western Kenya were analyzed. The study population included women age 18-65 years enrolled in HIV care. Screening uptake was calculated annually and overall, determining the proportion of eligible women screened. Multivariate logistic regression assessed predictors of positive screening outcomes. RESULTS There were 57,298 women living with HIV (WLWHIV) eligible for CCS across both programs during the study period. The mean age was 31.4 years (IQR, 25.9-37.8), and 39% were on antiretroviral therapy (ART) at the first CCS-eligible visit. Of all eligible women, 29.4% (95% CI, 29.1 to 29.8) underwent CCS during the study period, 27.0% (95% CI, 26.5 to 27.4) in the AMPATH program, and 35.6% (95% CI, 34.9 to 36.4) in the FACES program. Annual screening uptake varied greatly in both programs, with coverage as low as 1% of eligible WLWHIV during specific years. Age at first screening, CD4 count within 90 days of screening, current use of ART, and program (AMPATH v FACES) were each statistically significant predictors of positive screening. CONCLUSION CCS uptake at two large HIV care programs in Kenya fell short of the WHO's 70% screening target. Screening rates varied significantly on the basis of the availability of funding specific to CCS, reflecting the limitations of vertical funding programs.
Nonlinear Landauer formula for thermal transport of the electrons
Authors: Dong S. H. , Jia K. X. , Liu X. Y. , Geng H. , Sheng L. , Xing D. Y. 
Published: February 2024

Abstract
The Landauer formula, originally formulated in the context of linear transport, has been a powerful tool for studying quantum devices. However, recent research has shown that extending its application to nonlinear and nonreciprocal transport is crucial for a more comprehensive understanding. In this work, we develop a nonlinear Landauer formula for thermal transport of the electrons and apply it to investigate thermal transport in graphene. Our study reveals intriguing phenomena especially in the presence of large temperature gradients and at low system temperatures. At these conditions, higher-order nonlinear currents emerge, indicating the significance of nonlinear effects in thermal transport. Unlike thermoelectric conductivity, thermal conductivity can be decomposed into intrinsic and extrinsic terms. This decomposition is based on whether the contributions rely on the derivative of the transmission coefficient with respect to energy. This nonlinear Landauer formula presented here serves as a valuable tool for future investigations into the intricate interplay between temperature gradients, system temperatures, and thermal transport in quantum devices.