bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constructing lactylation-related genes prognostic model to effectively predict the disease-free survival and treatment responsiveness in prostate cancer based on machine learning
Authors: Pan Jinyou , Zhang Jianpeng , Lin Jingwei , Cai Yinxin , Zhao Zhigang 
Published: March 2024

Background: Prostate cancer (PCa) is one of the most common malignancies in men with a poor prognosis. It is therefore of great clinical importance to find reliable prognostic indicators for PCa. Many studies have revealed the pivotal role of protein lactylation in tumor development and progression. This research aims to analyze the effect of lactylation-related genes on PCa prognosis.Methods: By downloading mRNA-Seq data of TCGA PCa, we obtained the differential genes related to lactylation in PCa. Five machine learning algorithms were used to screen for lactylation-related key genes for PCa, then the five overlapping key genes were used to construct a survival prognostic model by lasso cox regression analysis. Furthermore, the relationships between the model and related pathways, tumor mutation and immune cell subpopulations, and drug sensitivity were explored. Moreover, two risk groups were established according to the risk score calculated by the five lactylation-related genes (LRGs). Subsequently, a nomogram scoring system was established to predict disease-free survival (DFS) of patients by combining clinicopathological features and lactylation-related risk scores. In addition, the mRNA expression levels of five genes were verified in PCa cell lines by qPCR.Results: We identified 5 key LRGs (ALDOA, DDX39A, H2AX, KIF2C, RACGAP1) and constructed the LRGs prognostic model. The AUC values for 1 -, 3 -, and 5-year DFS in the TCGA dataset were 0.762, 0.745, and 0.709, respectively. The risk score was found a better predictor of DFS than traditional clinicopathological features in PCa. A nomogram that combined the risk score with clinical variables accurately predicted the outcome of the patients. The PCa patients in the high-risk group have a higher proportion of regulatory T cells and M2 macrophage, a higher tumor mutation burden, and a worse prognosis than those in the low-risk group. The high-risk group had a lower IC50 for certain chemotherapeutic drugs, such as Docetaxel, and Paclitaxel than the low-risk group. Furthermore, five key LRGs were found to be highly expressed in castration-resistant PCa cells.Conclusion: The lactylation-related genes prognostic model can effectively predict the DFS and therapeutic responses in patients with PCa.
RET splice site variants in medullary thyroid carcinoma
Authors: Saeed-Vafa Daryoush , Chatzopoulos Kyriakos , Hernandez-Prera Juan , Cano Pedro , Saller James J. , Hallanger Johnson Julie E. , McIver Bryan , Boyle Theresa A. 
Published: March 2024

Introduction: Medullary thyroid carcinoma (MTC) is an aggressive cancer that is often caused by driver mutations in RET. Splice site variants (SSV) reflect changes in mRNA processing, which may alter protein function. RET SSVs have been described in thyroid tumors in general but have not been extensively studied in MTC.Methods: The prevalence of RET SSVs was evaluated in 3,624 cases with next generation sequence reports, including 25 MTCs. Fisher exact analysis was performed to compare RET SSV frequency in cancers with/without a diagnosis of MTC.Results: All 25 MTCs had at least one of the two most common RET SSVs versus 0.3% of 3,599 cancers with other diagnoses (p &lt; 0.00001). The 11 cancers with non-MTC diagnoses that had the common RET SSVs were 4 neuroendocrine cancers, 4 non-small cell lung carcinomas, 2 non-MTC thyroid cancers, and 1 melanoma. All 25 MTCs analyzed had at least one of the two most common RET SSVs, including 4 with no identified mutational driver.Discussion: The identification of RET SSVs in all MTCs, but rarely in other cancer types, demonstrates that these RET SSVs distinguish MTCs from other cancer types. Future studies are needed to investigate whether these RET SSVs play a pathogenic role in MTC.
Blood donation for iron removal in individuals with HFE mutations: study of efficacy and safety and short review on hemochromatosis and blood donation
Authors: Infanti Laura , Leitner Gerda , Moe Morten , Pehlic Vildana , Cattaneo Marco , Benkert Pascal , Holbro Andreas , Passweg Jakob , Worel Nina , Buser Andreas 
Published: March 2024

BackgroundElevated serum ferritin with/without HFE variants in asymptomatic persons leads frequently to referral for blood donation. Hemochromatosis (p.C282Y/p.C282Y) only requires treatment. We evaluated safety and feasibility of iron removal in healthy persons with elevated ferritin and HFE variants using blood donation procedures.Materials and methodsThirty subjects with ferritin &gt;200 ng/mL (women) or &gt;300 ng/mL (men) with p.C282Y/p.C282Y, p.C282Y/p.H63D or p.H63D/p.H63D were randomized to weekly phlebotomy (removal of 450 mL whole blood) or erythrapheresis (removal of 360 mL red blood cells) every 14 days. The ferritin target was &lt;100 ng/mL. A full blood count and ferritin were measured at each visit. Hemoglobin (Hb) ≥140 g/L was required at inclusion. If Hb dropped to &lt;120 g/L (women) or &lt;130 g/L (men), procedures were postponed (7 or 14 days). Primary endpoint was the number of procedures needed to the ferritin target; secondary objectives were duration of treatment and compliance. The treatment effect was tested with Poisson regression; number of procedures and treatment duration were compared between study arms with the Kruskal–Wallis test.ResultsTwenty-five of 30 participants were men (83%); mean age was 47 years (SD 10.5), mean BMI 26.6 kg/m2 (SD 3.6); 17 had p.C282Y/p.C282Y, nine p.C282Y/p.H63D, four p.H63D/p.H63D. Median baseline Hb was 150 g/L (IQR 144, 1,559), median ferritin 504 ng/mL (IQR 406,620). Twenty-seven subjects completed the study. Treatment arm (p &lt; 0.001) and HFE variant (p = 0.007) influenced the primary endpoint significantly. To ferritin levels &lt;100 ng/mL, a median number of 7.5 (IQR 6.2, 9.8) phlebotomies and 4.0 (IQR 3.0, 5.8) erythraphereses (p = 0.001) was needed during a median of 66.5 days (IQR 49,103) and 78.5 days (IQR 46139), respectively (p = 0.448). Low Hb was the principal reason for protocol violation; anemia occurred in 13 participants (48%). Immediate complications were infrequent; fatigue was reported after 25% of phlebotomies and 45% of erythraphereses. Thirty-five procedures were postponed because of low Hb and 15 for non-medical reasons. The median interval was 7.0 (IQR 7.7) and 14.0 (IQR 14, 20) days between phlebotomies and erythraphereses, respectively.ConclusionBlood donation procedures remove iron effectively in HC, but frequent treatments cause Hb decrease and fatigue that can impair feasibility.
Nomogram model of survival prediction for nasopharyngeal carcinoma with lung metastasis: developed from the SEER database and validated externally
Authors: Xiao Zhehao , Li Kaiguo , Su Fang , Yang Xiaohui , Zou Hongxing , Qu Song 
Published: March 2024

ObjectiveDistant metastasis occurs in some patients at the first diagnosis of nasopharyngeal carcinoma (NPC), the prognosis is poor, and there are significant individual differences. This study established a nomogram model of lung metastasis of NPC as a supplement to TNM staging.MethodsThe training cohort is used to build the nomogram model, and the validation cohort is used to evaluate the model. The training cohort of 177 patients is from the Surveillance, Epidemiology, and End Results (SEER) database. Factors affecting overall survival (OS) in patients with lung metastasis of NPC analysis by Cox regression analysis and then a nomogram were established. 122 patients from the Affiliated Tumor Hospital of Guangxi Medical University were selected as the external validation cohort. The concordance index (C-index), the area under the curve (AUC), and the calibration curve were used to assess the accuracy of the nomogram and used the decision curve analysis (DCA) curve to measure the clinical benefit capacity of the model. The patients were separated into two groups with different risks, and the “Kaplan-Meier (KM)” survival analysis was used to evaluate the differentiation ability of the model.ResultsAge, T-stage, radiation, chemotherapy, and brain metastases can affect the OS in NPC with lung metastasis. A nomogram was developed according to the above five factors. The C-index of the training cohort and the validation cohort were 0.726 (95% CI: 0.692-0.760) and 0.762 (95% CI: 0.733-0.791). The AUC of the nomogram was better than that of the TNM staging. In the training cohort, the nomogram predicted OS AUC values of 0.767, 0.746, and 0.750 at 1, 2, and 3 years, TNM stage of 0.574, 0.596, and 0.640. In the validation cohort, nomogram predictions of OS AUC values of 0.817, 0.857, and 0.791 for 1, 2, and 3 years, TNM stage of 0.575, 0.612, and 0.663. DCA curves suggest that nomogram have better clinical net benefits than TNM staging. The KM survival analysis shows that the nomogram has a reasonable risk stratification ability.ConclusionThis study successfully established a nomogram model of NPC lung metastasis, which can be used as a supplement to TNM staging and provide reference for clinicians.
Prevalence and predictive value of sarcopenia in surgically treated cholangiocarcinoma: a comprehensive review and meta-analysis
Authors: He Jie , Huang Yuanyuan , Huang Na , Jiang Jiaqing 
Published: March 2024

BackgroundSarcopenia, marked by a reduction in skeletal muscle mass and function, is a condition that can manifest in elderly patients with cancer and has been recognized as a possible adverse factor affecting the survival of individuals diagnosed with malignant tumors. This systematic review and meta-analysis aimed to examine the prevalence of sarcopenia in individuals with cholangiocarcinoma while concurrently investigating the potential correlations between the presence of sarcopenia and various critical factors, including survival outcomes and postoperative complications.MethodsA comprehensive search was conducted across multiple databases, including EMBASE, PubMed, Web of Science, Cochrane Library, and CNKI, employing keywords such as sarcopenia, cholangiocarcinoma, and prognosis. This research explored the prognostic value of sarcopenia on the survival of cholangiocarcinoma. The findings of this meta-analysis were presented using forest plots and a summarized effects model. The Newcastle-Ottawa Scale (NOS) was employed to evaluate the quality of the studies included in the analysis.ResultsA total of 33 articles from five databases were in in the quantitative analysis. A comprehensive meta-analysis revealed that the overall prevalence of sarcopenia among individuals diagnosed with cholangiocarcinoma was43%. Moreover, the analysis revealed a significant and noteworthy correlation between sarcopenia and key clinical parameters such as overall survival (OS), Recurrence-Free Survival (RFS), and Disease-Free Survival (DFS) in patients with cholangiocarcinoma. Subgroup analysis revealed that, when categorized by various ethnicities, diagnostic techniques, and tumor locations, sarcopenia consistently retained its status as a negative predictive factor. Furthermore, sarcopenia has emerged as a risk factor for postoperative complications. All included studies had an NOS score greater than 5, indicating a high quality of evidence.ConclusionThe results suggest that sarcopenia is significantly related to survival outcomes and postoperative complications in cholangiocarcinoma. Appropriate diagnosis and treatment of sarcopenia should be implemented to improve the prognosis of individuals with cholangiocarcinoma.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023479866, identifier CRD42023479866.
A systematic review and meta-analysis of radiotherapy and particle beam therapy for skull base chondrosarcoma: TRP-chondrosarcoma 2024
Authors: Nakamura Masatoshi , Mizumoto Masashi , Saito Takashi , Shimizu Shosei , Li Yinuo , Oshiro Yoshiko , Inaba Masako , Hosaka Sho , Fukushima Hiroko , Suzuki Ryoko , Iizumi Takashi , Nakai Kei , Maruo Kazushi , Sakurai Hideyuki 
Published: March 2024

IntroductionChondrosarcoma is a rare malignant bone tumor. Particle beam therapy (PT) can concentrate doses to targets while reducing adverse events. A meta-analysis based on a literature review was performed to examine the efficacy of PT and photon radiotherapy for skull base chondrosarcoma.MethodsThe meta-analysis was conducted using 21 articles published from 1990 to 2022.ResultsAfter PT, the 3- and 5-year overall survival (OS) rates were 94.1% (95% confidence interval [CI]: 91.0-96.2%) and 93.9% (95% CI: 90.6-96.1%), respectively, and the 3- and 5-year local control rates were 95.4% (95% CI: 92.0-97.4%) and 90.1% (95% CI: 76.8-96.0%), respectively. Meta-regression analysis revealed a significant association of PT with a superior 5-year OS rate compared to three-dimensional conformal radiotherapy (p &lt; 0.001). In the studies used in the meta-analysis, the major adverse event of grade 2 or higher was temporal lobe necrosis (incidence 1-18%, median 7%).ConclusionPT for skull base chondrosarcoma had a good outcome and may be a valuable option among radiotherapy modalities. However, high-dose postoperative irradiation of skull base chondrosarcoma can cause adverse events such as temporal lobe necrosis.
Psychosocial job characteristics comparison between work from home and work in the office: a study from the pandemic onwards
Authors: Picker-Roesch Clara , Schweiker Marcel , Kraus Thomas , Lang Jessica 
Published: March 2024

IntroductionThe Covid-19 pandemic changed office workers' work situation through the widespread use of the working from home (WFH) model. It also changed the demands for, and the resources allocated to, the same tasks depending on the location of their execution. The aim of this study was to identify potential differences in the level of theoretically established job stressors between WFH and regular office work, especially with respect to working parents with childcare responsibilities.MethodWe tested the relevant working conditions by conducting repeated online surveys with three measurement times between 2020 and 2022 (N = 1,144 in total).ResultsPaired sample t-tests for each measurement time showed significant differences between WFH and work in the office for six out of seven psychosocial risk factors (e.g., social relationships with supervisors and colleagues). Only work intensity did not differ between WFH and work in the office. The specific challenges for WFH parents caring for children were revealed in a decreased work continuity compared to employees without childcare responsibilities. Our results suggest that job stressors are contingent on the place of work.DiscussionIn conclusion, while WFH affords the opportunity to counterbalance job stressors in the long term, it requires the support of social relationships, especially for full-time WFH employees. Parents with childcare responsibilities require assistance in addressing their individual needs amidst the challenges of WFH.
Dapagliflozin versus sacubitril–valsartan for heart failure with mildly reduced or preserved ejection fraction
Authors: Arbel Ronen , Azab Abed N. , Oberoi Mansi , Aboalhasan Enis , Star Artyom , Elhaj Khaled , Khalil Fouad , Alnsasra Hilmi 
Published: March 2024

Background and aim:Heart failure with preserved ejection fraction (HFpEF) is associated with an increased risk of heart failure (HF) hospitalizations and cardiovascular death (CVD). Both dapagliflozin and sacubitril–valsartan have recently shown convincing reductions in the combined risk of CVD and HF hospitalizations in patients with HF and mildly reduced ejection fraction (HFmrEF) or HFpEF. We aimed to investigate the cost-per-outcome implications of dapagliflozin vs sacubitril–valsartan in the treatment of HFmrEF or HFpEF patients.Methods:We compared the annualized cost needed to treat (CNT) to prevent the composite outcome of total HF hospitalizations and CVD with dapagliflozin or sacubitril–valsartan. The CNT was estimated by multiplying the annualized number needed to treat (aNNT) by the annual cost of therapy. The aNNT was calculated based on data collected from the DELIVER trial for dapagliflozin and a pooled analysis of the PARAGLIDE-HF and PARAGON-HF trials for sacubitril–valsartan. Costs were based on 2022 US prices. Scenario analyses were performed to attenuate the differences in the studies’ populations.Results:The aNNT with dapagliflozin in DELIVER was 30 (95% confidence interval [CI]: 21-62) versus 44 (95% CI: 25-311) with sacubitril–valsartan in a pooled analysis of PARAGLIDE-HF and PARAGON-HF, with an annual cost of $4,951 and $5,576, respectively. The corresponding CNTs were $148,547.13 (95% CI: $103,982.99–$306,997.39) for dapagliflozin and $245,346.77 (95% CI: $139,401.58–1,734,155.60) for sacubitril–valsartan for preventing the composite outcome of CVD and HF hospitalizations. The CNT for preventing all-cause mortality was lower for dapagliflozin than sacubitril–valsartan $1,128,958.15 [CI: $401,077.24–∞] vs $2,185,816.71 [CI: $607,790.87–∞].Conclusion:Dapagliflozin provides a better monetary value than sacubitril–valsartan in preventing the composite outcome of total HF hospitalizations and CVD among patients with HFmrEF or HFpEF.
Comprehensive understanding of the mutant ‘giant’ Arthrospira platensis developed via ultraviolet mutagenesis
Authors: Lee Changsu , Han Sang-Il , Na Ho , Kim Zun , Ahn Joon Woo , Oh Byeolnim , Kim Hyun Soo 
Published: March 2024

IntroductionCyanobacteria are typically of a size that can be observed under a microscope. Here, we present cyanobacteria of a size that can be observed with the naked eye. Arthrospira platensis NCB002 strain showed differentiated morphological characteristics compared to previously reported Arthrospira spp.MethodsArthrospira platensis NCB002 was obtained by the UV irradiation of Arthrospira sp. NCB001, which was isolated from freshwater and owned by NCell Co., Ltd. A. platensis NIES-39 was obtained from the National Institute for Environmental Studies (Tsukuba, Japan). We used various analytical techniques to determine its overall characteristics.Results and discussionThe draft genome of strain NCB002 consists of five contigs comprising 6,864,973 bp with a G+C content of 44.3 mol%. The strain NCB002 had an average length of 11.69 ± 1.35 mm and a maximum of 15.15 mm, which is 23.4–50.5 times longer than the length (0.3–0.5 mm) of previously known Arthrospira spp., allowing it to be harvested using a thin sieve. Transcriptome analysis revealed that these morphological differences resulted from changes in cell wall formation mechanisms and increased cell division. Our results show that NCB002 has outstanding industrial value and provides a comprehensive understanding of it.
Insights from the Twittersphere: a cross-sectional study of public perceptions, usage patterns, and geographical differences of tweets discussing cocaine
Authors: Castillo-Toledo Consuelo , Fraile-Martínez Oscar , Donat-Vargas Carolina , Lara-Abelenda F. J. , Ortega Miguel Angel , Garcia-Montero Cielo , Mora Fernando , Alvarez-Mon Melchor , Quintero Javier , Alvarez-Mon Miguel Angel 
Published: March 2024

IntroductionCocaine abuse represents a major public health concern. The social perception of cocaine has been changing over the decades, a phenomenon closely tied to its patterns of use and abuse. Twitter is a valuable tool to understand the status of drug use and abuse globally. However, no specific studies discussing cocaine have been conducted on this platform.Methods111,508 English and Spanish tweets containing “cocaine” from 2018 to 2022 were analyzed. 550 were manually studied, and the largest subset underwent automated classification. Then, tweets related to cocaine were analyzed to examine their content, types of Twitter users, usage patterns, health effects, and personal experiences. Geolocation data was also considered to understand regional differences.ResultsA total of 71,844 classifiable tweets were obtained. Among these, 15.95% of users discussed the harm of cocaine consumption to health. Media outlets had the highest number of tweets (35.11%) and the most frequent theme was social/political denunciation (67.88%). Regarding the experience related to consumption, there are more tweets with a negative sentiment. The 9.03% of tweets explicitly mention frequent use of the drug. The continent with the highest number of tweets was America (55.44% of the total).DiscussionThe findings underscore the significance of cocaine as a current social and political issue, with a predominant focus on political and social denunciation in the majority of tweets. Notably, the study reveals a concentration of tweets from the United States and South American countries, reflecting the high prevalence of cocaine-related disorders and overdose cases in these regions. Alarmingly, the study highlights the trivialization of cocaine consumption on Twitter, accompanied by a misleading promotion of its health benefits, emphasizing the urgent need for targeted interventions and antidrug content on social media platforms. Finally, the unexpected advocacy for cocaine by healthcare professionals raises concerns about potential drug abuse within this demographic, warranting further investigation.
Serdexmethylphenidate/dexmethylphenidate for children with attention-deficit/hyperactivity disorder: dose optimization from a laboratory classroom study
Authors: Cutler Andrew J. , Kollins Scott H. , Brams Matthew N. , Corliss Meg , Oh Charles , Braeckman Rene , Childress Ann C. 
Published: March 2024

ObjectiveTo evaluate treatment responder rate using the Attention-Deficit/Hyperactivity Disorder Rating Scale-5 (ADHD-RS-5) score based on optimized dose level of serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) and changes in ADHD severity in children (aged 6–12 years) with ADHD.MethodsDuring a 21-day dose-optimization phase, 155 patients initiated treatment with 39.2/7.8 mg SDX/d-MPH in the first week and then were titrated to an optimum dose; 5 patients were downtitrated to 26.1/5.2 mg, 76 were uptitrated to 52.3/10.4 mg, and 69 remained at 39.2/7.8 mg during the following 2 weeks. Responder threshold values were 30% and 50% based on the percent change from baseline (day 0) to days 7, 14, and 21 in the ADHD-RS-5 score. The Conners 3rd Edition-Parent score was used to assess weekly changes in ADHD severity during the dose-optimization and treatment phases.ResultsOf the 5 subjects whose dose was optimized at 26.1/5.2 mg, ≥80% across all days had ≥50% responder rate. Of the 69 subjects whose dose was optimized at 39.2/7.8 mg, 81.2% had ≥50% responder rate by day 21. Of the 76 subjects whose dose was optimized to 52.3/10.4 mg, 72.4% had ≥50% responder rate by day 21. Changes in ADHD severity, based on mean Conners 3rd Edition-Parent scores, improved from baseline at each visit during dose optimization for each subscale. At the dose-optimization phase, Conners 3rd Edition-Parent scores improved from baseline for SDX/d-MPH in all subscales.ConclusionA high percentage of subjects were responders upon reaching their final optimized dose. SDX/d-MPH demonstrated significant reductions in ADHD severity in children based on the Conners 3rd Edition-Parent scores. Determining the optimal dosage of SDX/d-MPH and its effect on ADHD severity could enable the development of a more clinically relevant treatment regimen in children with ADHD.