bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review of primary large cell neuroendocrine carcinoma of the prostate
Authors: Nguyen Ngan , Franz Ronald Dean , Mohammed Omar , Huynh Richard , Son Christine Kim , Khan Rida Nusrat , Ahmed Bilawal 
Published: March 2024

BackgroundLarge cell neuroendocrine carcinoma (LCNEC) is a rare subtype of prostate cancer. The pathogenesis, clinical manifestation, treatment options, and prognosis are uncertain and underreported.Materials and methodsA systematic search was conducted in April 2022 through PubMed, Embase, and Cochrane. We reviewed cases of LCNEC developed either from de novo or transformation from prostate adenocarcinoma and summarized the relevant pathophysiological course, treatment options, and outcomes.ResultsA total of 25 patients with a mean age of 70.4 (range 43 87 years old) from 18 studies were included in this review. 13 patients were diagnosed with de novo LCNEC of the prostate. 12 patients were from the transformation of adenocarcinoma post-hormonal therapy treatment. Upon initial diagnosis, patients diagnosed with de novo prostatic LCNEC had a mean serum PSA value of 24.6 ng/ml (range: 0.09-170 ng/ml, median 5.5 ng/ml), while transformation cases were significantly lower at 3.3 ng/ml (range: 0-9.3 ng/ml, median 0.05 ng/ml). The pattern of metastasis closely resembles prostate adenocarcinoma. Six out of twenty-three cases displayed brain metastasis matching the correlation between neuroendocrine tumors and brain metastasis. Three notable paraneoplastic syndromes included Cushings syndrome, dermatomyositis, and polycythemia. Most patients with advanced metastatic disease received conventional platinum-based chemotherapy with a mean survival of 5 months. There was one exception in the transformation cohort with a somatic BRCA2 mutation who was treated with a combination of M6620 and platinum-based chemotherapy with an impressive PFS of 20 months. Patients with pure LCNEC phenotype have worse survival outcomes when compared to those with mixed LCNEC and adenocarcinoma phenotypes. It is unclear whether there is a survival benefit to administering ADT in pure pathologies.ConclusionLCNEC of the prostate is a rare disease that can occur de novo or transformation from prostatic adenocarcinoma. Most patients present at an advanced stage with poor prognosis and are treated with conventional chemotherapy regimens. Patients who had better outcomes were those who were diagnosed at an early stage and received treatment with surgery or radiation and androgen deprivation therapy (ADT). There was one case with an exceptional outcome that included a treatment regimen of M6620 and chemotherapy.
Sulforaphane inhibits the growth of prostate cancer by regulating the microRNA-3919/DJ-1 axis
Authors: Zhang Fangxi , Wan Xiaofeng , Zhan Jianmin , Shen Ming , Li Runsheng 
Published: March 2024

BackgroundProstate cancer (PCa) is the second most common solid cancer among men worldwide and the fifth leading cause of cancer-related deaths in men. Sulforaphane (SFN), an isothiocyanate compound, has been shown to exert inhibitory effects on a variety of cancers. However, the biological function of SFN in PCa has not been fully elucidated. The objective of this study was conducted to further investigate the possible underlying mechanism of SFN in PCa using in vitro cell culture and in vivo tumor model experiments.MethodsCell viability, migration, invasion, and apoptosis were analyzed by Cell Counting Kit-8 (CCK-8), wound healing assay, transwell assay, or flow cytometry. Expression of microRNA (miR)-3919 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) or in situ hybridization assay. Xenograft assay was conducted to validated the antitumor effect of miR-3919. The targeting relationship between miR-3919 and DJ-1 was verified by dual-luciferase reporter assay. The level of DJ-1was measured by qRT-PCR or western blotting (WB).ResultsIn the present study, SFN downregulated mRNA and protein expression of DJ-1, an oncogenic gene. Small RNA sequencing analysis and dual-luciferase reporter assay confirmed that microRNA (miR)-3919 directly targeted DJ-1 to inhibition its expression. Furthermore, miR-3919 overexpression impeded viability, migration, and invasion and promoted apoptosis of PCa cells. Tumor growth in nude mice was also inhibited by miR-3919 overexpression, and miR-3919 expression in PCa tissues was lower than that in peritumoral tissues in an in situ hybridization assay. Transfection with miR-3919 inhibitors partially reversed the effects of SFN on cell viability, migration, invasion, and apoptosis. ConclusionOverall, the miR-3919/DJ-1 axis may be involved in the effects of SFN on the malignant biological behavior of PCa cells, which might be a new therapeutic target in PCa.
Reintegration into school, kindergarten and work in families of childhood cancer survivors after a family-oriented rehabilitation program
Authors: Inhestern Laura , Nasse Mona L. , Krauth Konstantin A. , Kandels Daniela , Rutkowski Stefan , Escherich Gabriele , Bergelt Corinna 
Published: March 2024

ObjectiveTo describe the situation of childhood cancer survivors and their parents before and one year after a family-oriented rehabilitation program (FOR) and to identify factors influencing reintegration.MethodsWe included parents of children diagnosed with leukemia or central nervous system tumor. We assessed parental functioning using the functioning subscale of the Ulm Quality of Life Inventory for Parents (ULQIE) and children's school/kindergarten related quality of life (parental assessment, subscale KINDL-R). Descriptive analyses, group comparisons and multiple regression analyses on data of 285 parents of 174 children diagnosed with leukemia or central nervous system tumor.ResultsParents reported changes in their work situation (e.g., reduction of working hours) due to their child's diagnosis. Parental functioning increased significantly over time. Children's leukemia diagnosis and shorter time since the end of treatment were associated with higher functioning in parents one year after FOR. Parents reported difficulties in the child's work pace, concentration, stress resilience and empathy. The school/kindergarten-related quality of life (QoL) of the children was lower than in the general population. One year after FOR, most children reintegrated fully in school/kindergarten, partly with support (e.g., integration assistant). No significant predictors for children's reintegration were identified.DiscussionParents and children experience major changes in their work/school/kindergarten life. One year after FOR most parents reported a reintegration of their children, however the children's school/kindergarten-related QoL remained below average compared to norm values. Even after rehabilitation families of childhood cancer survivors might benefit from psychosocial and practical support offers to support families with the reintegration into work/school/kindergarten.
Elasticity and cross-sectional thickness of paraspinal muscles in progressive adolescent idiopathic scoliosis
Authors: Fan Yunli , Zheng Haiping , Feng Lin , To Michael K. T. , Kuang Guan-Ming , Yeung Eric H. K. , Cheung Kenneth M. C. , Liu Li , Cheung Jason P. Y. 
Published: March 2024

Objectives(1) Compare the cross-sectional thickness (CST) and shear wave speed (SWS) of paraspinal muscles (PSM) in adolescent idiopathic scoliosis (AIS) with and without curve progression; (2) investigate the relationship between CST/SWS and radiographic characteristics in AIS with curve progression; (3) compare the CST/SWS between AIS and non-scoliosis controls.MethodsThis cross-sectional study analyzed the CST and SWS of PSM in 48 AIS with mild to moderate curvature and 24 non-scoliosis participants. Participants with scoliosis greater than 45° of Cobb angles were excluded. The Change of Cobb angles within the last 6-months was retrieved to allocate AIS into progression and non-progression groups. The SWS and CST of multifidus; longissimus and iliocostalis of the major curve were measured using B-mode ultrasound image with an elastography mode. Discrepancies of the SWS (SWS-ratio: SWS on the convex side divided by SWS on the concave side) and CST (CST-ratio: CST on the convex side divided by CST on the concave side) at the upper/lower end and apical vertebrae were studied.ResultsA higher SWS at the apical vertebrae on the concave side of the major curve (multifidus: 3.9 ± 1.0 m/s vs. 3.1 ± 0.6 m/s; p &lt; 0.01, longissimus: 3.3 ± 1.0 m/s vs. 3.0 ± 0.9 m/s; p &lt; 0.01, iliocostalis: 2.8 ± 1.0 m/s vs. 2.5 ± 0.8 m/s; p &lt; 0.01) was observed in AIS with curve progression. A lower SWS-ratio at apical vertebrae was detected with a greater vertebral rotation in participants with curve progression (multifidus [grade II]: 0.7 ± 0.1 vs. grade I: 0.9 ± 0.2; p = 0.03, longissimus [grade II]: 0.8 ± 0.2 vs. grade I: 1.1 ± 0.2; p &lt; 0.01). CST was not different among the progressive, non-progressive AIS and non-scoliosis controls.ConclusionsIncreased SWS of PSM without change of CST was observed on the concave side of the major curve in participants with progressive AIS.
Ferric citrate for the treatment of hyperphosphatemia and iron deficiency anaemia in patients with NDD-CKD: a systematic review and meta-analysis
Authors: Ding Xueying , Sun Shujie , Zhang Jinjin , Zhao Huifang , Lun Fenglan , Liu Xuemin , Zhen Yiwan , Dong Jinping , Wu Jingliang 
Published: March 2024

Background: The application of ferric citrate therapy has yielded unexpected benefits in recent years for Chronic kidney disease patients suffering from hyperphosphatemia and iron deficiency -anaemia. Despite this, earlier research on the impact of ferric citrate on NDD-CKD has been contentious.Objective: The goal of the meta-analysis is to evaluate the evidence regarding the advantages and dangers of ferric citrate for the treatment of hyperphosphatemia and iron deficiency anaemia in NDD-CKD patients.Methods: Between the start of the study and June 2022, we searched PubMed, Embase, Cochrane, EBSCO, Scopus, Web of Science, Wan Fang Data, CNKI, and VIP databases for randomised controlled trials of iron citrate for hyperphosphatemia and anaemia in patients with NDD-CKD. For binary categorical data, risk ratios (OR) were employed, and for continuous variables, weighted mean differences The effect sizes for both count and measurement data were expressed using 95% confidence intervalsResults: The meta-analysis includes eight trials with a total of 1281 NDD-CKD patients. The phosphorus-lowering effect of ferric citrate was greater compared to the control group (WMD, −0.55, 95% CI, −0.81 to −0.28; I2 = 86%, p &lt; 0.001). Calcium (WMD, 0.092; 95% CI, −0.051 to 0.234; p &gt; 0.05; I2 = 61.9%), PTH (WMD, −0.10; 95% CI, −0.44 to 0.23; I2 = 75%, p &gt; 0.05) and iFGF23 (WMD, −7.62; 95% CI, −21.18 to 5.94; I2 = 20%, p &gt; 0.05) levels were not statistically different after ferric citrate treatment compared to control treatment. Furthermore, ferric citrate increased iron reserves and haemoglobin. The ferric citrate group had considerably greater levels than the controls. Ferric citrate, on the other hand, may raise the risk of constipation, diarrhoea, and nausea.Conclusion: This meta-analysis found that ferric citrate had a beneficial effect in the treatment of NDD-CKD, particularly in reducing blood phosphorus levels when compared to a control intervention. It also shown that ferric citrate has a favourable effect on iron intake and anaemia management. In terms of safety, ferric citrate may increase the likelihood of gastrointestinal side effects.
Leaf extract of Garcinia atroviridis promotes anti-heat stress and antioxidant effects in Caenorhabditis elegans
Authors: Chuaijit Sirithip , Punsawad Chuchard , Winoto Veronica , Plaingam Waluga , Kongkaew Itti , Phetcharat Atidtaya , Ichikawa Takafumi , Kubo Makoto , Kawakami Fumitaka , Tedasen Aman , Chatatikun Moragot 
Published: March 2024

Introduction:Garcinia atroviridis has been used for traditional medicines, healthy foods and tea. The chemical compositions and biological activities of fruit, stem bark and root have been widely studied. However, the phytochemical components and the biological activities in Garcinia atroviridis leaves (GAL) are limited. This research aims to study the phytochemical components and the stress resistance effects of GAL in Caenorhabditis elegans (C. elegans).Methods: To investigate the chemical components and antioxidant activities of GAL extract, the ethanol extract was characterized by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF MS) analysis and C. elegans was used to evaluate the effects of GAL extracts on longevity and stress resistance.Results and discussion: The results revealed that the ethanol extract of GAL possesses free radical scavenging activities. Furthermore, GAL extract increased the lifespan of C. elegans by 6.02%, 15.26%, and 12.75% at concentrations of 25, 50, and 100 μg/mL, respectively. GAL extract exhibited improved stress resistance under conditions of heat and hydrogen peroxide-induced stress. The survival rates of GAL extract-treated worms were significantly higher than those of untreated worms, and GAL extract reduced reactive oxygen species (ROS) accumulation. Additionally, GAL extract treatment upregulated the expression of stress resistance-associated genes, including gst-4, sod-3, skn-1, and hsp16.2. GAL extract supplementation alleviated stress and enhanced longevity by inducing stress-related genes in C. elegans. The observed effects of GAL extracts may be attributed to the stimulation of oxidant enzymes mediated through DAF-16/FOXO and SKN-1/NRF2, as well as the enhancement of thermal defense in C. elegans. Collectively, this study provides the first evidence of the antioxidant activities of GAL and elucidates the underlying mechanisms of stress resistance.
Next generation risk assessment: an ab initio case study to assess the systemic safety of the cosmetic ingredient, benzyl salicylate, after dermal exposure
Authors: Ebmeyer Johanna , Najjar Abdulkarim , Lange Daniela , Boettcher Mareike , Voß Silja , Brandmair Katrin , Meinhardt Jaqueline , Kuehnl Jochen , Hewitt Nicola J. , Krueger Christopher-Tilman , Schepky Andreas 
Published: March 2024

We performed an ab initio next-generation risk assessment (NGRA) for a fragrance ingredient, benzyl salicylate (BSal), to demonstrate how cosmetic ingredients can be evaluated for systemic toxicity endpoints based on non-animal approaches. New approach methodologies (NAMs) used to predict the internal exposure included skin absorption assays, hepatocyte metabolism, and physiologically based pharmacokinetic (PBPK) modeling, and potential toxicodynamic effects were assessed using pharmacology profiling, ToxProfiler cell stress assay, transcriptomics in HepG2 and MCF-7 cells, ReproTracker developmental and reproductive toxicology (DART) assays, and cytotoxicity assays in human kidney cells. The outcome of the NGRA was compared to that of the traditional risk assessment approach based on animal data. The identification of the toxicologically critical entity was a critical step that directed the workflow and the selection of chemicals for PBPK modeling and testing in bioassays. The traditional risk assessment and NGRA identified salicylic acid (SA) as the “toxdriver.” A deterministic PBPK model for a single-day application of 1.54 g face cream containing 0.5% BSal estimated the Cmax for BSal (1 nM) to be much lower than that of its major in vitro metabolite, SA (93.2 nM). Therefore, SA was tested using toxicodynamics bioassays. The lowest points of departure (PoDs) were obtained from the toxicogenomics assays. The interpretation of these results by two companies and methods were similar (SA only results in significant gene deregulation in HepG2 cells), but PoD differed (213 μM and 10.6 µM). A probabilistic PBPK model for repeated applications of the face cream estimated the highest Cmax of SA to be 630 nM. The resulting margins of internal exposure (MoIE) using the PoDs were 338 and 16, which were more conservative than those derived from external exposure and in vivo PoDs (margin of safety values were 9,705). In conclusion, both traditional and ab initio NGRA approaches concluded that the daily application of BSal in a cosmetic leave-on face cream at 0.5% is safe for humans. The processing and interpretation of toxicogenomics data can lead to different PoDs, which can subsequently affect the calculation of the MoIE. This case study supports the use of NAMs in a tiered NGRA ab initio approach.
Adverse reactions induced by MDT/WHO (Rifampicin+Clofazimine+Dapsone) and ROM (Rifampicin+Ofloxacin+Minocycline) regimens used in the treatment of leprosy: a cohort study in a National Reference Center in Brazil
Authors: Celestino Isadora Costa , Antunes Douglas Eulalio , Santos Diogo Fernandes , Gimenes Victor Lemos , de Souza Fabiane Mian , Goulart Isabela Maria Bernardes 
Published: March 2024

Background: Recommended standard treatment for leprosy is multidrugtherapy (MDT/WHO), consisting Rifampicin+Dapsone+Clofazimine. Other medications are recommended in cases of resistance, adverse reactions and intolerances, including ROM regimen, Rifampicin+Ofloxacin+Minocycline. Therefore, pharmacovigilance is an important tool in understanding these adverse drug reactions (ADRs), supporting pharmacotherapy management and medication safety. This study seeks to evaluate ADRs comparing two therapeutic regimens, MDT and ROM, used in treatment of patients with leprosy, analyzing prognostic factors regarding risk and safety.Methods:A retrospective cohort study was performed by assessing medical records of 433 patients diagnosed with leprosy from 2010 to 2021 at a National Reference Center in Brazil. They were subject to 24 months or more of treatment with MDT or ROM regimens. ADR assessments were analyzed by two experienced researchers, who included clinical and laboratory variables, correlating them with temporality, severity and the causality criteria of Naranjo and WHO.Results: The findings observed an average of 1.3 reactions/patient. Out of individuals experiencing reactions, 67.0% (69/103) were utilizing MDT/MB, while 33.0% (34/103) were using ROM. The median time for ADR of 79 days for MDT and 179 days for ROM. In first reaction, Dapsone was the most frequently involved medication; the most affected system was hematopoietic. As compared to Clofazimine, results indicated that use of Dapsone was associated with 7% increased risk of ADR occurrence (HR: 1.07; p = 0.866). Additionally, Rifampicin was linked to 31% increased risk of ADRs (HR: 1.31; p = 0.602); and Ofloxacin showed 35% elevated risk (HR: 1.35; p = 0.653). Conversely, results for Minocycline indicated 44% reduction in the risk of ADRs (HR: 0.56; p = 0.527), although statistical significance was not reached. The use of MDT conferred 2.51 times higher risk of developing ADRs in comparison to ROM.Conclusion: The comparison between MDT and ROM revealed that MDT caused more ADRs, and these reactions were more severe, indicating less safety for patients. Dapsone was the most common medication causing ADRs, followed by Rifampicin. The combination with Clofazimine was associated with an additional risk of ADRs, warranting further studies to confirm this hypothesis. Given the high magnitude of ADRs, healthcare teams need to monitor patients undergoing leprosy treatment with focus on pharmacovigilance.
In vivo screening for toxicity-modulating drug interactions identifies antagonism that protects against ototoxicity in zebrafish
Authors: Bustad Ethan , Mudrock Emma , Nilles Elizabeth M. , Mcquate Andrea , Bergado Monica , Gu Alden , Galitan Louie , Gleason Natalie , Ou Henry C. , Raible David W. , Hernandez Rafael E. , Ma Shuyi 
Published: March 2024

Introduction: Ototoxicity is a debilitating side effect of over 150 medications with diverse mechanisms of action, many of which could be taken concurrently to treat multiple conditions. Approaches for preclinical evaluation of drug-drug interactions that might impact ototoxicity would facilitate design of safer multi-drug regimens and mitigate unsafe polypharmacy by flagging combinations that potentially cause adverse interactions for monitoring. They may also identify protective agents that antagonize ototoxic injury.Methods: To address this need, we have developed a novel workflow that we call Parallelized Evaluation of Protection and Injury for Toxicity Assessment (PEPITA), which empowers high-throughput, semi-automated quantification of ototoxicity and otoprotection in zebrafish larvae via microscopy. We used PEPITA and confocal microscopy to characterize in vivo the consequences of drug-drug interactions on ototoxic drug uptake and cellular damage of zebrafish lateral line hair cells.Results and discussion: By applying PEPITA to measure ototoxic drug interaction outcomes, we discovered antagonistic interactions between macrolide and aminoglycoside antibiotics that confer protection against aminoglycoside-induced damage to lateral line hair cells in zebrafish larvae. Co-administration of either azithromycin or erythromycin in zebrafish protected against damage from a broad panel of aminoglycosides, at least in part via inhibiting drug uptake into hair cells via a mechanism independent from hair cell mechanotransduction. Conversely, combining macrolides with aminoglycosides in bacterial inhibition assays does not show antagonism of antimicrobial efficacy. The proof-of-concept otoprotective antagonism suggests that combinatorial interventions can potentially be developed to protect against other forms of toxicity without hindering on-target drug efficacy.
Association between adult attachment and mental health states among health care workers: the mediating role of social support
Authors: Yang Yahui , Chen Kaichao , Liang Kaiwen , Du Wanyi , Guo Jiamei , Du Lian 
Published: March 2024

BackgroundTo determine the relationships between attachment style, social support, and mental health states, as well as the mediation mechanism within this relationship, we conducted a survey among healthcare workers during the coronavirus disease 2019 (COVID-19) epidemic quarantine.MethodsThe survey assessed their mental health states, adult attachment style, social support, and some other relevant information. Mental health states were represented by the overall state of sleep, physical and emotional assessment. A multiple mediator model was used to explain how social support could mediate the relationship between attachment and mental health states during COVID-19 quarantine.ResultsOur findings revealed that 33.3% of the participants experienced emotional issues, 8.5% had sleep problems, and 24.9% reported physical discomfort. The direct effect of adult attachment styles on mental health states during COVID-19 quarantine was significant (c′ = −0.3172;p&lt; 0.01). The total indirect effect also showed statistical significance (ab = −0.1857;p&lt; 0.01). Moreover, the total effect of adult attachment styles on mental health states was −0.5029 (c = −0.5029;p&lt; 0.01). Subjective social support and utilization of social support play mediating roles in the relationship between attachment style and mental health states, respectively (ab1= −0.1287, 95% CI: −0.9120 to −0.3341, ab2= 0.0570, 95% CI: −0.4635 to −0.1132).ConclusionThese findings highlight social support played a mediation role between attachment style and mental health states. Thus, offering social support during a crisis might be useful for those individuals with an insecure attachment.