bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonlinear relationship between serum 25-hydroxyvitamin D and lipid profile in Chinese adults
Authors: Wang Qianqian , Miao Xinlei , Hu Manling , Xu Fei , Tang Guimin , He Yangxuan , Song Ziping , Zhao Wan , Niu Xiangjun , Leng Song 
Published: June 2024

BackgroundPrevious studies on the liner associations between serum 25-hydroxyvitamin D [25(OH)D] levels and lipid profiles revealed ambiguous findings. The current study therefore tried to elucidate the possible non-linear associations between 25(OH)D and lipid profiles.MethodsThis study involved 8,516 adult participants (aged 18–74 years, males N = 3,750, females N = 4,766) recruited from the Dalian health management cohort (DHMC). The risk (OR) for specific dyslipidemias was estimated across the serum 25(OH)D levels and the cut-off value for serum 25(OH)D were determined by using logistic regression, restricted cubic spline, and piecewise linear regression methods, adjusted for age, sex, season, and ultraviolet index.ResultsIn this study, a high prevalence of 25(OH)D deficiency was observed in the participants (65.05%). The level of 25(OH)D showed the inverse U-shaped correlations with the risks (ORs) of abnormal lipid profile, with inflection points observed at 23.7 ng/ml for hypercholesterolemia, 24.3 ng/ml for hypertriglyceridemia, 18.5 ng/ml for hyper-low-density lipoprotein cholesterolemia, 23.3 ng/ml for hypo-high-density lipoprotein cholesterolemia, 23.3 ng/ml for hyper-non-high-density lipoprotein cholesterol, and 24.3 ng/ml for high remnant cholesterol. The stratified analyses showed that the risk for most dyslipidemias related to deficiency of 25(OH)D was particularly increased among females aged 50–74 (except for hypertriglyceridemia, where the highest risk was among men aged 50–74 years), during winter/spring or under low/middle ultraviolet index environments.ConclusionsNonlinear inverse U-shaped associations were observed between 25(OH)D levels and abnormal lipid profile. The risk was particularly increased among females aged 50-74, during winter/spring period or under lower ultraviolet index environments. In vitamin D deficient subjects [25(OH)D &lt;20 ng/ml], a positive association of serum vitamin D levels with the risk for dyslipidemia was observed, which needs a further.
Single institution experience of MRI-guided radiotherapy for thoracic tumors and clinical characteristics impacting treatment duty cycle
Authors: Miccio Joseph A. , Potter Nicholas J. , Showkat Anaum , Yao Min , Mahase Sean , Ferenci Michele , Sisley Kaitlin , Dailey Amy , Knipple Jamie , Blakely Amy , Tuanquin Leonard , Machtay Mitchell 
Published: June 2024

IntroductionMRI-guided radiotherapy (MRgRT) allows for direct motion management and real-time radiation treatment plan adaptation. We report our institutional experience using low strength 0.35T MRgRT for thoracic malignancies, and evaluate changes in treatment duty cycle between first and final MRgRT fractions.MethodsAll patients with intrathoracic tumors treated with MRgRT were included. The primary reason for MRgRT (adjacent organ at risk [OAR] vs. motion management [MM] vs. other) was recorded. Tumor location was classified as central (within 2cm of tracheobronchial tree) vs. non-central, and further classified by the Expanded HILUS grouping. Gross tumor volume (GTV) motion, planning target volume expansions, dose/fractionation, treatment plan time, and total delivery time were extracted from the treatment planning system. Treatment plan time was defined as the time for beam delivery, including multileaf collimator (MLC) motion, and gantry rotation. Treatment delivery time was defined as the time from beam on to completion of treatment, including treatment plan time and patient respiratory breath holds. Duty cycle was calculated as treatment plan time/treatment delivery time. Duty cycles were compared between first and final fraction using a two-sample t-test.ResultsTwenty-seven patients with thoracic tumors (16 non-small cell lung cancer and 11 thoracic metastases) were treated with MRgRT between 12/2021 and 06/2023. Fifteen patients received MRgRT due to OAR and 11 patients received MRgRT for motion management. 11 patients had central tumors and all were treated with MRgRT due to OAR risk. The median dose/fractionation was 50 Gy/5 fractions. For patients treated due to OAR (n=15), 80% had at least 1 adapted fraction during their course of radiotherapy. There was no plan adaptation for patients treated due to motion management (n=11). Mean GTV motion was significantly higher for patients treated due to motion management compared to OAR (16.1mm vs. 6.5mm, p=0.011). Mean duty cycle for fraction 1 was 54.2% compared to 62.1% with final fraction (p=0.004). Mean fraction 1 duty cycle was higher for patients treated due to OAR compared to patients treated for MM (61% vs. 45.0%, p=0.012).DiscussionDuty cycle improved from first fraction to final fraction possibly due to patient familiarity with treatment. Duty cycle was improved for patients treated due to OAR risk, likely due to more central location and thus decreased target motion.
Late events after anti-CD19 CAR T-cell therapy for relapsed/refractory B-cell non-Hodgkin lymphoma
Authors: Cordeiro Ana Costa , Durisek George , Batista Marjorie Vieira , Schmidt Jayr , de Lima Marcos , Bezerra Evandro 
Published: June 2024

BackgroundThe short-term complications from chimeric antigen receptor T-cell therapy (CART) are well characterized, but the long-term complications still need to be further investigated. Therefore, herein, we will review the currently available literature published on the late adverse events following CART.MethodsWe reviewed published data available from pivotal trials and real-world experiences with anti-CD19 CART (CART19) for adults with lymphoma. We defined late events as occurring or persisting beyond 1 month after CART infusion. We focused our literature review on the following late-event outcomes post-CART19: cytopenia, immune reconstitution, infections, and subsequent malignancies.ResultsGrade 3–4 cytopenia beyond 30 days occurs in 30%–40% of patients and beyond 90 days in 3%–22% of patients and is usually managed with growth-factor and transfusion support, along with neutropenic prophylaxis. B-cell aplasia and hypogammaglobulinemia are expected on-target off-tumor effects of CART19, 44%–53% of patients have IgG &lt; 400 mg/dL, and approximately 27%–38% of patients receive intravenous immunoglobulin (IVIG) replacement. Infections beyond the initial month from CART19 are not frequent and rarely severe, but they are more prevalent and severe when patients receive subsequent therapies post-CART19 for their underlying disease. Late neurotoxicity and neurocognitive impairment are uncommon, and other causes should be considered. T-cell lymphoma (TCL) after CART is an extremely rare event and not necessarily related to CAR transgene. Myeloid neoplasm is not rare post-CART, but unclear causality given heavily pretreated patient population is already at risk for therapy-related myeloid neoplasm.ConclusionCART19 is associated with clinically significant long-term effects such as prolonged cytopenia, hypogammaglobulinemia, and infections that warrant clinical surveillance, but they are mostly manageable with a low risk of non-relapse mortality. The risk of subsequent malignancies post-CART19 seems low, and the relationship with CART19 and/or prior therapies is unclear; but regardless of the possible causality, this should not impact the current benefit–risk ratio of CART19 for relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).
Cervical cancer awareness, perception, and attitude among tertiary health institution students in northeastern Nigeria
Authors: Muhammad Zakia B. , Ezenkwa Uchenna S. , Imoudu Iragbogie A. , Katagum Dauda A. , Usman Iliyasu , George Sophia H. L. , Schlumbrecht Matthew , Audu Bala M. 
Published: June 2024

BackgroundThe devastating scourge of cervical cancer in Africa is largely due to the absence of preventive interventions, driven by low awareness and poor perception of the disease in the continent. This work is a preliminary effort toward understanding key social drivers promoting this disease in our immediate environment with a view to mitigating it.MethodFemale students of two tertiary health institutions in Azare, northeastern Nigeria, were approached to participate in this cross-sectional descriptive study. A structured self-administered questionnaire was administered to consenting participants and covered questions on their socio-demographics, awareness, perception, and attitude about/toward cervical cancer and its prevention. The responses were scrutinized for coherency and categorized into themes using summary statistics, while a chi-square test was used to determine the association between awareness of cervical cancer and participant age, marital status, religion, screening uptake, and willingness to undergo screen.ResultsAwareness of cervical cancer was recorded among 174/230 (75.7%) respondents who enrolled in this study; 117 (67.2%) knew that it was preventable, but only three (1.3%) respondents had undergone screening. Among the aware participants, 91 (52.3%) and 131 (75.3%) knew that sexual intercourse and multiple sexual partners are risk factors for the disease, respectively. In contrast, knowledge of the etiology was poor; 82 (47.1%) respondents who knew it was preventable had heard about human papillomavirus (HPV), while 72 (41.4%) knew that HPV causes cervical cancer. Most (78%) of the participants expressed willingness to take a human papillomavirus vaccine or undergo screening (84.6%) if made available to them. Awareness was significantly associated with participants’ age (p = 0.022) and willingness to undergo screening (p = 0.016).ConclusionThis study revealed discordance between awareness and knowledge about cervical cancer. Educational initiatives reflective of population perception/knowledge of cervical cancer are needed to mitigate the rising incidence of this disease, especially among female healthcare providers.
Cost-effectiveness of durvalumab plus tremelimumab in combination with chemotherapy for the treatment of metastatic non-small-cell lung cancer from the US healthcare sector’s and societal perspectives
Authors: Gan Yena , Shi Fenghao , Zhu He , Li Huangqianyu , Han Sheng , Li Duoduo 
Published: June 2024

PurposeMetastatic non-small cell lung cancer (mNSCLC) has a high incidence rate, and economic burdens to patients, healthcare systems, and societies. Durvalumab plus tremelimumab and chemotherapy (T+D+CT) is a novel therapeutic strategy for mNSCLC, which demonstrated promising efficacy in a phase-3 randomized clinical trial, but its economic value remains unclear.MethodsThis economic evaluation used a hypothetical cohort of patients with mNSCLC, with characteristics mirroring those of the participants in the POSEIDON trial. Several partitioned survival models were constructed to estimate 15-year costs and health outcomes associated with the T+D+CT, durvalumab plus chemotherapy (D+CT) and chemotherapy alone (CT) strategies, discounting costs and effectiveness at 3% annually. Costs were in 2023 US dollars. Data were derived from the POSEIDON trial and published literature. Deterministic and probabilistic sensitivity analyses were performed to assess the uncertainty of input parameters and study generalizability. The analysis was designed and conducted from September 2022 to March 2023. To evaluate the cost-effectiveness of T+D+CT, compared with CT and D+CT, for mNSCLC from the perspectives of the US healthcare sector and society.FindingsFrom the healthcare sector’s perspective, the T+D+CT yielded an additional 0.09 QALYs at an increased cost of $7,108 compared with CT, which resulted in an ICER of $82,501/QALY. The T+D+CT strategy yielded an additional 0.02 QALYs at an increased cost of $27,779 compared with the D+CT, which resulted in an ICER of $1,243,868/QALY. The economic results of T+D+CT vs. CT were most sensitive to the annual discount rate, subsequent immunotherapy cost, tremelimumab cost, palliative care and death cost, pemetrexed cost, and durvalumab cost. The T+D+CT strategy was considered cost-effective relative to CT in 59%–82% of model iterations against willingness-to-pay. thresholds of $100,000/QALY gained to $150,000/QALY gained. From the societal perspective, the T+D+CT can be considered as cost-effective as compared with CT or D+CT, independent of histology.ImplicationsIn this cost-effectiveness analysis, the T+D+CT strategy represented good value compared with CT for patients with mNSCLC from the perspectives of the healthcare sector and the society. This treatment strategy may be prioritized for mNSCLC patients at high risks of disease progression.
IL-23 inhibitor enhances the effects of PTEN DNA-loaded lipid nanoparticles for metastatic CRPC therapy
Authors: Chen Xinlu , Gong Luyao , Wang Yuanyuan , Ye Chen , Guo Huanhuan , Gao Shen , Chen Jiyuan , Wang Zhuo , Gao Yuan 
Published: June 2024

Introduction: Metastatic castration-resistant prostate cancer (mCRPC) patients face challenges due to limited treatment options. About 50% of patients with mCRPC have a functional loss of phosphatase and tensin homology deleted on chromosome 10 (PTEN), leading to tumor progression, metastasis, and immune suppression. Moreover, elevated IL-23 produced by myeloid-derived suppressor cells (MDSCs) is found in CRPC patients, driving tumor progression. Therefore, a combination strategy based on PTEN restoration and IL-23 inhibition may block CRPC progression and metastasis.Methods: The antitumor effect of restoring PTEN expression combined with the IL-23 inhibitor Apilimod was studied in a mouse model of bone metastasis CRPC and mouse prostate cancer RM-1 cells. To verify the targeting ability of PTEN DNA coated with lipid nanoparticles (LNP@PTEN) in vitro and in vivo. In addition, RT-qPCR and flow cytometry were used to investigate the related mechanisms of the antitumor effect of LNP@PTEN combined with Apilimod.Results: LNPs exhibited significant tumor-targeting and tumor accumulation capabilities both in vitro and in vivo, enhancing PTEN expression and therapeutic efficacy. Additionally, the combination of LNP@PTEN with the IL-23 inhibitor Apilimod demonstrated enhanced inhibition of tumor growth, invasion, and metastasis (particularly secondary organ metastasis) compared to other groups, and extended the survival of mice to 41 days, providing a degree of bone protection. These effects may be attributed to the PTEN function restoration combined with IL-23 inhibition, which help reverse immune suppression in the tumor microenvironment by reducing MDSCs recruitment and increasing the CD8+/CD4+ T cell ratio.Discussion: In summary, these findings highlight the potential of LNPs for delivering gene therapeutic agents. And the combination of LNP@PTEN with Apilimod could achieve anti-tumor effects and improve tumor microenvironment. This combinational strategy opens new avenues for the treatment of mCRPC.
Cystic fibrosis: desensitization in delayed hypersensitivity reactions to elexacaftor/tezacaftor/ivacaftor
Authors: Gómez-Ganda L. , Galván-Blasco P. , Fernández-Polo A. , Cardona V. , García-Palop B. , Parramón-Teixidó CJ , Polverino E. , Álvarez-Fernández A. 
Published: June 2024

Background: Cystic fibrosis transmembrane conductance regulator modulators are the only available treatment for cystic fibrosis. Although elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is well-tolerated, rash has been reported as very frequent. In severe rashes, ELX/TEZ/IVA withdrawal is necessary, leading to clinical deterioration. The objective of the study is to increment the experience of ELX/TEZ/IVA desensitization.Methods: Adult patients who developed a delayed hypersensitivity rash to ELX/TEZ/IVA between December 2021 and February 2023 and required withdrawal due to ineffective rescue medication were included. Skins test for ELX/TEZ/IVA and IVA were conducted to establish hypersensitivity mechanism. Balijepally ELX/TEZ/IVA desensitization protocol was selected. In cases where desensitization had to be discontinued due to rash, an extended desensitization was proposed. Clinical and health-related quality of life parameters were collected before ELX/TEZ/IVA and after desensitization.Results: 162 patients (81 women, 31.2 [23.8–42.5] years) started ELX/TEZ/IVA, developing rash 12 of them (7.4%, six women). Six patients (five women) required stopping ELX/TEZ/IVA and were selected for desensitization. Skin tests indicated delayed type-IV hypersensitivity in one patient. Two patients presented adequate tolerance to desensitization; while, four patients developed rash. Three of these patients, successfully concluded extended desensitization (one patient declined participation). No significant clinical deterioration or quality of life worsening was observed during desensitization; in fact, there was an improvement in practically all mesured parameters. All five patients who resumed ELX/TEZ/IVA are currently receiving therapy with good tolerance.Conclusion: Desensitization to ELX/TEZ/IVA could be a successful and safe strategy for reintroducing this essential treatment in cases of a delayed hypersensitivity rash.
The potential neuroprotective effects of cannabinoids against paclitaxel-induced peripheral neuropathy: in vitro study on neurite outgrowth
Authors: Creanga-Murariu Ioana , Filipiuc Leontina-Elena , Gogu Maria-Raluca , Ciorpac Mitica , Cumpat Carmen Marinela , Tamba Bogdan-Ionel , Alexa-Stratulat Teodora 
Published: June 2024

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a shared burden for 68.1% of oncological patients undergoing chemotherapy with Paclitaxel (PTX). The symptoms are intense and troublesome, patients reporting paresthesia, loss of sensation, and dysesthetic pain. While current medications focus on decreasing the symptom intensity, often ineffective, no medication is yet recommended by the guidelines for the prevention of CIPN. Cannabinoids are an attractive option, as their neuroprotective features have already been demonstrated in neuropathies with other etiologies, by offering the peripheral neurons protection against toxic effects, which promotes analgesia.Methods: We aim to screen several new cannabinoids for their potential use as neuroprotective agents for CIPN by investigating the cellular toxicity profile and by assessing the potential neuroprotective features against PTX using a primary dorsal root ganglion neuronal culture.Results: Our study showed that synthetic cannabinoids JWH-007, AM-694 and MAB-CHMINACA and phytocannabinoids Cannabixir® Medium dried flowers (NC1) and Cannabixir® THC full extract (NC2) preserve the viability of fibroblasts and primary cultured neurons, in most of the tested dosages and time-points. The combination between the cannabinoids and PTX conducted to a cell viability of 70%–89% compared to 40% when PTX was administered alone for 48 h. When assessing the efficacy for neuroprotection, the combination between cannabinoids and PTX led to better preservation of neurite length at all tested time-points compared to controls, highly drug and exposure-time dependent. By comparison, the combination of the cannabinoids and PTX administered for 24 h conducted to axonal shortening between 23% and 44%, as opposed to PTX only, which shortened the axons by 63% compared to their baseline values.Discussion and Conclusion: Cannabinoids could be potential new candidates for the treatment of paclitaxel-induced peripheral neuropathy; however, our findings need to be followed by additional tests to understand the exact mechanism of action, which would support the translation of the cannabinoids in the oncological clinical practice.
Medicinal plants used by traditional medicine practitioners in treatment of alcohol-related disorders in Bushenyi District, southwestern Uganda
Authors: Maling Samuel , Kabakyenga Jerome , Muchunguzi Charles , Olet Eunice Apio , Namaganda Mary , Kahwa Ivan , Alele Paul Erasmus 
Published: June 2024

BackgroundAlcohol-related disorders rank seventh among risk factors for morbidity and mortality globally, posing a significant public health burden. In Africa, including Uganda, there is limited availability and utilization of pharmacotherapies to treat alcohol-related disorders. This study documented medicinal plant species, plant parts used, and the methods of preparation and administration utilized by Traditional Medicine Practitioners (TMPs) in treating alcohol-related disorders in southwestern Uganda.MethodsA descriptive cross-sectional ethnopharmacological survey was conducted among TMPs within Bushenyi District, southwestern Uganda. Data was collected with key informant interviews using semi-structured questionnaires. The TMPs identified medicinal plants by local names. Plant specimens were collected and deposited at the Department of Biology, Faculty of Science, Mbarara University for identification and voucher numbers allocated. The plant scientific names and species were identified based on the International Plant Names Index. Plant species, family, life form, number of mentions, method of collection, preparation and administration were analyzed using descriptive statistics in Microsoft Excel. The survey data were utilized to compute Frequency of Citation, Relative Frequency of Citation, and Informant Consensus Factor.ResultsWe enrolled 50 traditional medicine practitioners aged between 34 and 98 years, with a mean age of 67. Approximately two-thirds were female (66%, 33/50), and mean experience in traditional healing was 31 years. The total number of plants identified were 25 belonging to 20 families. The most prevalent plant life form was herbs (36%) while grasses (4%), were the least. Leaves (48%) were the most utilized plant parts with the least utilized being the barks. The most prevalent method, adopted by approximately one-third of the TMPs, involved drying the plant material in the sun. The Informant Consensus Factor was 0.67.ConclusionThe study shows that the traditional medicine practitioners in Bushenyi district use a wide diversity of plants species to treat alcohol related disorders. The relatively high Informant Consensus Factor suggests a significant level of agreement among TMPs regarding the use of the identified plants. We recommend further investigations into phytochemistry, safety, efficacy, and mechanisms of action of the identified plants.