bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison analysis of PD-1/PD-L1 inhibitors plus lenvatinib or gemcitabine/cisplatin as first-line treatment for patients with advanced intrahepatic cholangiocarcinoma
Authors: Huang Jia-Xin , Liu Bo , Li Yu , Li Xi , Ding Li-Juan , Wang Nan-Ya 
Published: August 2023

BackgroundIntrahepatic cholangiocarcinoma (ICC) is a highly aggressive primary liver cancer, with increasing incidence worldwide. Effective first-line treatments for advanced ICC patients are currently limited. Therefore, our study aimed to assess the efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors in combination with gemcitabine/cisplatin (GC) and lenvatinib as first-line treatment in advanced ICC patients.MethodsThis retrospective cohort study included 51 advanced ICC patients, among whom 25 patients were administered with PD-1/PD-L1 plus lenvatinib and 26 patients were administered with PD-1/PD-L1 plus GC. Baseline characteristics including demographic information, medical history, clinical characteristics, laboratory data, and imaging examination were collected. The primary endpoints were progression-free survival (PFS) and sixth- and ninth-month overall survival (OS) rate. Survival curve was plotted by the Kaplan–Meier method. A Cox proportion risk model was performed to investigate independent risk factors of PFS and OS. The secondary outcomes were objective response rate (ORR), disease control rate (DCR), and adverse events.ResultsThe median age of advanced ICC patients in our study was 58.0 (95% confidence interval [95% CI] = 48.0–72.4) years, with 33 male and 18 female patients. Patients in the PD-1/PD-L1 inhibitors plus lenvatinib group were more likely to be in ECOG grade above 1, develop ascites, and have an elevated level of ALT. The ORR was 16.0% in the PD-1/PD-L1 inhibitors plus lenvatinib group and 23.1% in the GC group (p = 0.777). The DCR was 52.0% in the lenvatinib group and 46.2% in the GC group (p = 0.676). The combination treatment of PD-1/PD-L1 inhibitors plus lenvatinib was associated with longer PFS than the GC group; however, it was not statistically significant (lenvatinib: 9.5 months, GC: 5.1 months, p = 0.454). The sixth-month and ninth-month OS rates were 82.0% and 76.9% in the lenvatinib group and 87.4% and 71.5% in the GC group. After adjusting for confounders, multivariate Cox regression analysis showed that ECOG grade above 1 was an independent risk factor for PFS (hazard ratio [HR] = 3.388, 95% CI = 1.312–8.746, p = 0.012) and OS (HR = 4.220, 95% CI = 1.131–15.742, p = 0.032).ConclusionPD-1/PD-L1 inhibitors in combination with lenvatinib or GC all demonstrated significant efficacy and safety as first-line treatment in patients with advanced ICC. As for patients who refuse or are intolerant to chemotherapy, PD-1/PD-L1 plus lenvatinib would be recommended.
Landscape of germline BRCA1/BRCA2 variants in breast and ovarian cancer in Peru
Authors: Ferreyra Yomali , Rosas Gina , Cock-Rada Alicia M. , Araujo Jhajaira , Bravo Leny , Doimi Franco , Casas Jhoysi , Clavo María de los Ángeles , Pinto Joseph A. , Belmar-López Carolina 
Published: August 2023

BackgroundThere is an increasing amount of data from Latin America on the characterization of BRCA variants; however, there is limited information from Peru. We conducted a retrospective study to describe germline pathogenic/likely pathogenic(P/LP) variants and variants of uncertain/unknown significance (VUS) in the BRCA1 and BRCA2 genes in Peru, in patients with breast and ovarian cancer, candidates for treatment with poly (adenosine diphosphate–ribose) polymerase (PARP) inhibitors.MethodsThe patients were evaluated during the period 2019-2021. Genomic DNA was isolated from peripheral blood samples and targeted sequencing was performed using the Ampliseq BRCA panel. Genetic variant interpretation was carried out in accordance with the recommendations of the American College of Medical Genetics and ClinVar. During this period, 525 patients (143 with breast cancer and 382 with ovarian cancer) were studied. ResultsWe found that 14.7% (21/143) of breast cancer patients and 20.7% (79/382) of ovarian cancer patients were carriers of P/LP variants in BRCA1/2. The most frequent pathogenic variants detected in BRCA1 were c.2105dupT (BIC: 2224insT, n=12, 18.75%), c.68_69delAG (BIC: 185delAG, n=6, 9.38%), c.140G&gt;T and c.815_824dupAGCCATGTGG (n=5, 7.81%), while in BRCA2 were c.8023A&gt;G (n=6, 16.67%), c.6024dupG (BIC: 6252insG, n=4, 11.11%), and c.9235delG (BIC: 9463delG, n=3, 8.33%). Regarding VUS, we found that 6.99% (10/143) of breast cancer patients and 7.33% (28/382) of ovarian cancer patients were carriers of a VUS in BRCA1/2. For BRCA1, the most frequent VUS was c.93C&gt;G (n=2), and for BRCA2, c.5465A&gt;T (n=4), c.3101T&gt;C (n=3), c.205C&gt;A and c.437T&gt;C (n=2). ConclusionWe found a frequency of 14.7% germline mutations in breast cancer patients and 20.7% in ovarian cancer patients. The most recurrent mutations were BRCA1 c.2105dupT and BRCA2 c.8023A&gt;G. We found that BRCA2 c.8023A&gt;G, c.6024dupG, and c.9235delG were not previously reported in Peruvian patients. BRCA1 c.2344dupA is a novel mutation that has not been previously reported in any database. The frequency of VUS in our cohort was 7.2%.
A systematic review of progress on hepatocellular carcinoma research over the past 30 years: a machine-learning-based bibliometric analysis
Authors: Lee Kiseong , Hwang Ji Woong , Sohn Hee Ju , Suh Sanggyun , Kim Sun-Whe 
Published: August 2023

IntroductionResearch on hepatocellular carcinoma (HCC) has grown significantly, and researchers cannot access the vast amount of literature. This study aimed to explore the research progress in studying HCC over the past 30 years using a machine learning-based bibliometric analysis and to suggest future research directions.MethodsComprehensive research was conducted between 1991 and 2020 in the public version of the PubMed database using the MeSH term “hepatocellular carcinoma.” The complete records of the collected results were downloaded in Extensible Markup Language format, and the metadata of each publication, such as the publication year, the type of research, the corresponding author’s country, the title, the abstract, and the MeSH terms, were analyzed. We adopted a latent Dirichlet allocation topic modeling method on the Python platform to analyze the research topics of the scientific publications.ResultsIn the last 30 years, there has been significant and constant growth in the annual publications about HCC (annual percentage growth rate: 7.34%). Overall, 62,856 articles related to HCC from the past 30 years were searched and finally included in this study. Among the diagnosis-related terms, “Liver Cirrhosis” was the most studied. However, in the 2010s, “Biomarkers, Tumor” began to outpace “Liver Cirrhosis.” Regarding the treatment-related MeSH terms, “Hepatectomy” was the most studied; however, recent studies related to “Antineoplastic Agents” showed a tendency to supersede hepatectomy. Regarding basic research, the study of “Cell Lines, Tumors,’’ appeared after 2000 and has been the most studied among these terms.ConclusionThis was the first machine learning-based bibliometric study to analyze more than 60,000 publications about HCC over the past 30 years. Despite significant efforts in analyzing the literature on basic research, its connection with the clinical field is still lacking. Therefore, more efforts are needed to convert and apply basic research results to clinical treatment. Additionally, it was found that microRNAs have potential as diagnostic and therapeutic targets for HCC.
Baseline whole-lung CT features deriving from deep learning and radiomics: prediction of benign and malignant pulmonary ground-glass nodules
Authors: Huang Wenjun , Deng Heng , Li Zhaobin , Xiong Zhanda , Zhou Taohu , Ge Yanming , Zhang Jing , Jing Wenbin , Geng Yayuan , Wang Xiang , Tu Wenting , Dong Peng , Liu Shiyuan , Fan Li 
Published: August 2023

ObjectiveTo develop and validate the model for predicting benign and malignant ground-glass nodules (GGNs) based on the whole-lung baseline CT features deriving from deep learning and radiomics.MethodsThis retrospective study included 385 GGNs from 3 hospitals, confirmed by pathology. We used 239 GGNs from Hospital 1 as the training and internal validation set; 115 and 31 GGNs from Hospital 2 and Hospital 3 as the external test sets 1 and 2, respectively. An additional 32 stable GGNs from Hospital 3 with more than five years of follow-up were used as the external test set 3. We evaluated clinical and morphological features of GGNs at baseline chest CT and extracted the whole-lung radiomics features simultaneously. Besides, baseline whole-lung CT image features are further assisted and extracted using the convolutional neural network. We used the back-propagation neural network to construct five prediction models based on different collocations of the features used for training. The area under the receiver operator characteristic curve (AUC) was used to compare the prediction performance among the five models. The Delong test was used to compare the differences in AUC between models pairwise.ResultsThe model integrated clinical-morphological features, whole-lung radiomic features, and whole-lung image features (CMRI) performed best among the five models, and achieved the highest AUC in the internal validation set, external test set 1, and external test set 2, which were 0.886 (95% CI: 0.841-0.921), 0.830 (95%CI: 0.749-0.893) and 0.879 (95%CI: 0.712-0.968), respectively. In the above three sets, the differences in AUC between the CMRI model and other models were significant (all P &lt; 0.05). Moreover, the accuracy of the CMRI model in the external test set 3 was 96.88%.ConclusionThe baseline whole-lung CT features were feasible to predict the benign and malignant of GGNs, which is helpful for more refined management of GGNs.
A real-world pharmacovigilance analysis of FDA adverse event reporting system database for upadacitinib
Authors: Wu Yan , Wei Meihao , Zhang Jing 
Published: August 2023

Objective: To mine the adverse drug event (ADE) signals of upadacitinib based on the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to provide a reference for the safe clinical use of the drug.Methods: The ADE data for upadacitinib from Q1 2004 to Q1 2023 in the FAERS database were retrieved, and data mining was performed using the reporting odds ratio and proportional reporting ratio.Results: A total of 21,213 ADE reports for the primary suspect drug upadacitinib were obtained, involving 444 ADEs. Patients aged ≥60 years (21.48%) and female (70.11%) patients were at a higher risk of ADEs with upadacitinib. After data cleaning, 182 ADE signals from 19 system organ classes (SOCs) were obtained. Six of these SOCs that occurred more frequently and were not mentioned in the drug labeling information included renal and urinary system (1.09%), reproductive and breast diseases (1.14%), ear and labyrinth disorders (0.57%), psychiatric disease (0.57%), blood and lymphatic system disorders (0.57%), and endocrine disorders (0.57%). The top ten most frequent ADE signals reported for upadacitinib were mainly related to: infections and infestations (7), investigations (2), and skin and subcutaneous tissue disorders (1). The top 10 ADEs in signal intensity ranking were lip neoplasm, ureteral neoplasm, eczema herpeticum, vulvar dysplasia, mediastinum neoplasm, eosinopenia, herpes zoster cutaneous disseminated, eye ulcer, acne cystic, and Moraxella infection. The top 10 high-frequency events leading to serious adverse events were urinary tract infection (2.74%), herpes zoster (1.63%), diverticulitis (1.19%), bronchitis (0.68%), nasopharyngitis (0.68%), localised infection (0.66%), nephrolithiasis (0.66%), pulmonary thrombosis (0.66%), blood cholesterol increased (0.55%), and Pneumocystis jirovecii pneumonia (0.53%).Conclusion: Clinicians should be vigilant to upadacitinib-induced events in systems not covered in the drug labeling information and to new and highly signaled ADEs to ensure the safe and effective use of upadacitinib.
A novel role of the splenic volume in Crohn’s disease: evaluating the efficacy of infliximab
Authors: Shi Xuan , Wang Jia-Hui , Rao Sheng-Xiang , Liu Tao-Tao , Wu Hao 
Published: August 2023

Background: A number of patients with Crohn’s disease (CD) suffer from loss of response to infliximab (IFX) therapy. Splenic volume is reported to be enlarged in patients with CD compared to normal individuals. The association between splenic volume and IFX efficacy in CD remains unclear.Methods: We performed a retrospective study of patients with CD who received regular IFX treatment at Zhongshan Hospital, Fudan University, between August 2015 and December 2021. We collected baseline characteristics and clinical features from medical records in the CD database of Zhongshan Hospital. We accurately measured the splenic volume using semi-auto spleen segmentation software, followed by the analysis of splenic volume and IFX efficacy.Results: We included 49 patients with CD receiving IFX treatment, of whom 41 responded to IFX and 8 failed to respond to IFX. Splenic volume, as well as volume adjusted for body mass index (SV/BMI) and body weight (SV/W), was significantly decreased after IFX treatment in responders but increased in non-responders compared to the volume before the treatment. Accordingly, the levels of leukocyte count, platelet count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were decreased after IFX treatment in responders. Contrarily, the levels of hemoglobin, albumin, and tumor necrosis factor (TNF)-α were elevated in responders. Moreover, both CRP and TNF-α levels were significantly positively correlated with SV/BMI in all patients.Conclusion: Splenic volume, especially SV/BMI and SV/W, was reduced after IFX treatment in CD patients responsive to IFX. SV/BMI was positively correlated with disease activity. Splenic volume is a promising indicator to evaluate IFX efficacy in CD.
Carnitine metabolites and cognitive improvement in patients with schizophrenia treated with olanzapine: a prospective longitudinal study
Authors: Zhao Lei , Liu Hua , Wang Wenjuan , Wang Youping , Xiu Meihong , Li Shuyun 
Published: August 2023

Objective: Cognitive impairment is one of the core symptoms of schizophrenia, which is stable and lifelong. L-carnitine has been shown to improve cognitive function and decrease the rate of cognitive deterioration in patients with Alzheimer’s disease. However, it remains unclear regarding the role of L-carnitine and its metabolites in cognitive functions in schizophrenia after treatment with olanzapine. The purpose of this study was to evaluate the relationship between changes in plasma levels of L-carnitine metabolites and cognitive improvement after olanzapine treatment.Methods: This was a prospective longitudinal study. In this study, we recruited 25 female patients with first episode schizophrenia (FES) who were drug naïve at baseline and received 4 weeks of olanzapine monotherapy. Cognitive function was assessed at baseline and 4-week follow-up using the RBANS. Plasma L-carnitine metabolite levels were determined by a metabolomics technology based on untargeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS).Results: We found that the immediate memory index, delayed memory index and RBANS composite score were significantly increased at the 4-week follow-up after treatment. A total of 7 differential L-carnitine metabolites were identified in FES patients after olanzapine monotherapy. In addition, we found that changes in butyrylcarnitine were positively correlated with improvements in language index and RBANS composite score. Further regression analyses confirmed the association between reduced butyrylcarnitine levels and cognitive improvement after olanzapine monotherapy in FES patients.Conclusion: Our study shows that cognitive improvement after olanzapine treatment was associated with changes in L-carnitine metabolite levels in patients with FES, suggesting a key role of L-carnitine in cognition in schizophrenia.
Effect of varying UAV height on the precise estimation of potato crop growth
Authors: Njane Stephen Njehia , Tsuda Shogo , van Marrewijk Bart M. , Polder Gerrit , Katayama Kenji , Tsuji Hiroyuki 
Published: August 2023

A phenotyping pipeline utilising DeepLab was developed for precisely estimating the height, volume, coverage and vegetation indices of European and Japanese varieties. Using this pipeline, the effect of varying UAV height on the precise estimation of potato crop growth properties was evaluated. A UAV fitted with a multispectral camera was flown at a height of 15 m and 30 m in an experimental field where various varieties of potatoes were grown. The properties of plant height, volume and NDVI were evaluated and compared with the manually obtained parameters. Strong linear correlations with R2 of 0.803 and 0.745 were obtained between the UAV obtained plant heights and manually estimated plant height when the UAV was flown at 15 m and 30 m respectively. Furthermore, high linear correlations with an R2 of 0.839 and 0.754 were obtained between the UAV-estimated volume and manually estimated volume when the UAV was flown at 15 m and 30 m respectively. For the vegetation indices, there were no observable differences in the NDVI values obtained from the UAV flown at the two heights. Furthermore, high linear correlations with R2 of 0.930 and 0.931 were obtained between UAV-estimated and manually measured NDVI at 15 m and 30 m respectively. It was found that UAV flown at the lower height had a higher ground sampling distance thus increased resolution leading to more precise estimation of both the height and volume of crops. For vegetation indices, flying the UAV at a higher height had no effect on the precision of NDVI estimates.
Low soil available phosphorus level reduces cotton fiber length via osmoregulation
Authors: Sun Miao , Zheng Cangsong , Feng Weina , Shao Jingjing , Pang Chaoyou , Li Pengcheng , Dong Helin 
Published: August 2023

IntroductionPhosphorus (P) deficiency hinders cotton (Gossypium hirustum L.) growth and development, seriously affecting lint yield and fiber quality. However, it is still unclear how P fertilizer affects fiber length.MethodsTherefore, a two-year (2019-2020) pool-culture experiment was conducted using the split-plot design, with two cotton cultivars (CCRI-79; low-P tolerant and SCRC-28; low-P sensitive) as the main plot. Three soil available phosphorus (AP) contents (P0: 3 ± 0.5, P1: 6 ± 0.5, and P2 (control) with 15 ± 0.5 mg kg−1) were applied to the plots, as the subplot, to investigate the impact of soil AP content on cotton fiber elongation and length. ResultsLow soil AP (P0 and P1) decreased the contents of the osmotically active solutes in the cotton fibers, including potassium ions (K+), malate, soluble sugar, and sucrose, by 2.2–10.2%, 14.4–47.3%, 8.7–24.5%, and 10.1–23.4%, respectively, inhibiting the vacuoles from facilitating fiber elongation through osmoregulation. Moreover, soil AP deficiency also reduced the activities of enzymes participated in fiber elongation (plasma membrane H+-ATPase (PM-H+-ATPase), vacuole membrane H+-ATPase (V-H+-ATPase), vacuole membrane H+-translocating inorganic pyrophosphatase (V-H+-PPase), and phosphoenolpyruvate carboxylase (PEPC)). The PM-H+-ATPase, V-H+-ATPase, V-H+-PPase, and PEPC were reduced by 8.4–33.0%, 7.0–33.8%, 14.1–38.4%, and 16.9–40.2%, respectively, inhibiting the transmembrane transport of the osmotically active solutes and acidified conditions for fiber cell wall, thus limiting the fiber elongation. Similarly, soil AP deficiency reduced the fiber length by 0.6–3.0 mm, mainly due to the 3.8–16.3% reduction of the maximum velocity of fiber elongation (VLmax). Additionally, the upper fruiting branch positions (FB10–11) had higher VLmax and longer fiber lengths under low soil AP. DiscussionCotton fibers with higher malate content and V-H+-ATPase and V-H+-PPase activities yielded longer fibers. And the malate and soluble sugar contents and V-H+-ATPase and PEPC activities in the SCRC-28's fiber were more sensitive to soil AP deficiency in contrast to those of CCRI-79, possibly explaining the SCRC-28 fiber length sensitivity to low soil AP.
The significance of feeling safe for resilience of adolescents in sub-Saharan Africa
Authors: Bandeira Monica , Graham Marien A. , Ebersöhn Liesel 
Published: August 2023

IntroductionAdolescents in sub-Saharan Africa (SSA) are exposed to several challenges and risk factors, linked to historical legacies. Sub-Saharan Africa has one of the highest rates of poverty and inequality in the world, is one of the regions most negatively affected by climate change, performs poorly on many health measures, and has high rates of different forms of violence, especially gender-based violence. These contextual challenges impact adolescent mental health outcomes, preventing them to access resilience-enabling pathways that support positive outcomes despite adversity. This study aimed to contribute to knowledge generation on resilience of young people in the understudied SSA region by investigating which variables directly (or indirectly) affect the resilience of adolescents.MethodsPurposive sampling was used to collect quantitative survey data from 3,312 adolescents (females = 1,818; males = 1,494) between the ages of 12 and 20 years, participating in interventions implemented by a non-governmental organization, the Regional Psychosocial Support Initiative. Data were collected in Angola (385, 11.6%), Eswatini (128, 3.9%), Kenya (390, 11.8%), Lesotho (349, 10.5%), Mozambique (478, 14.4%), Namibia (296, 8.9%), South Africa (771, 23.3%), Uganda (201, 6.1%), and Zambia (314, 9.5%). The survey collected data on socio-demographic status, resilience (CYRM-R), depression (PHQ-9), self-esteem (Rosenberg Self-Esteem Scale) and feelings of safety (self-developed scale). Mental health was defined as lower levels of depression, higher levels of self-esteem and higher levels of feeling safe. A mediation analysis was conducted to investigate the relationship between the predictors (the socio-demographic variables) and the output (resilience), with the mediators being depression, self-esteem and feeling safe (which all link to mental health).ResultsThis study contributes to a gap in knowledge on country-level comparative evidence on significant predictors that impact resilience outcomes (directly or indirectly) for adolescents in sub-Saharan African countries. The results indicate that, when considering all countries collectively, feeling safe is the only predictor that has a significant direct effect on overall resilience and personal resilience, but not on caregiver resilience. When considering each country separately, feeling safe has a direct effect on overall, personal and caregiver resilience for all countries; but not for South Africa and Mozambique.DiscussionThe results provide evidence on which to craft youth development interventions by measuring mediators (depression, self-esteem and feeling safe) and resilience for adolescents in sub-Saharan Africa. The overall results of the present paper point toward a contextually relevant pathway to supporting their resilience, namely, the need to systemically target the creation and/or strengthening of structures that enable adolescents to feel safe.