bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost per NNT for upadacitinib in the treatment of patients with moderate-severe atopic dermatitis in Italy
Authors: Chiricozzi Andrea , Costanzo Antonio , Levi Anna , Parretta Federica , Ravasio Roberto 
Published: February 2024

Background: Targeted systemic therapies, including abrocitinib, baricitinib, dupilumab, tralokinumab and upadacitinib, are new treatments for moderate to severe atopic dermatitis (AD). We evaluated the efficacy and the costs of these targeted systemic therapies in the treatment of adult patients with moderate to severe AD.
Methods: The clinical efficacy was assessed considering the results of a previous network meta-analysis (NMA). The analysis involved five therapies approved in Italy for the treatment of moderate to severe AD: abrocitinib (ABR), baricitinib (BAR), dupilumab (DUP), tralokinumab (TRA) and upadacitinib (UPA). According to the NMA, the cost of the treatment was based on the number of administrations dispensed at 16 weeks and the clinical efficacy was measured by the number needed to treat (NNT) compared to placebo using the improvement ≥ 75% (EASI-75) or ≥ 90 (EASI-90) from baseline of the eczema area and severity index (EASI). Only the ex-factory price of the targeted systemic therapies was considered. The cost per NNT was adopted as a cost-effectiveness indicator.
Results: At 16 weeks, the cost per NNT based on EASI-75 was lower for UPA 15 mg (€ 6,384.00) compared to BAR 4 mg (€ 11,619.73) and 2 mg (€ 14,524.66), ABR 100 mg (€ 16,265.22), DUP 300 mg (€ 16,115.04) and TRA 300 mg (€ 31,710.24). UPA 15 (€ 8,512.00) also showed the lower cost per NNT based on EASI-90 at 16 weeks compared to BAR 4 mg (€ 14,788.75) and 2 mg (€ 20,862.70), ABR 100 mg (€ 25,922.69), DUP 300 mg (€ 25,992.00) and TRA 300 mg (€ 41,067.36).
Conclusions: The findings show that upadacitinib is the most cost-effective option (cost per NNT) for the treatment of moderate to severe atopic dermatitis.
A REPRESENTAÇÃO DAS PERSONAGENS MULHERES NA SÉRIE DINAMARQUESA FORBRYDELSEN
Authors: Ribeiro Gabriela Quadros 
Published: February 2024

Este trabalho, parte da monografia de conclusão do curso de Cinema e Audiovisualda Unespar, tem como objetivo realizar uma análise da construção e representação daspersonagens femininas na produção seriada dinamarquesa Forbrydelsen, que é uma dasprecursoras do fenômeno atual das protagonistas detetives mulheres na TV. Partindo deteorias feministas relacionadas ao condicionamento do olhar em relação às personagensfemininas, o artigo busca indicar como se dá essa representação, tanto narrativamentequanto em relação a escolhas de linguagem audiovisual. A partir de episódios selecionadosdentre os 40 que compõem as quatro temporadas da série, busca-se ainda estabelecer quelugar essas mulheres ocupam dentro da narrativa em relação aos personagens masculinos,passando pelos conceitos de passividade e atividade, bem como questões relacionadas í sexualidade, famí­lia e trabalho. Por fim, em se tratando de linguagem, busca-se entenderqual o olhar que se tem sobre essa mulher, tanto dentro da série quanto fora dela, no quese refere ao olhar que se determina que o espectador tenha, tendo em vista ainda o opostoe questionando se essas mulheres também detêm o poder do olhar.PALAVRAS-CHAVE: Representação feminina. Forbrydelsen. Série televisiva criminal.
Interplay between mitochondrial dysfunction and lysosomal storage: challenges in genetic metabolic muscle diseases with a focus on infantile onset Pompe disease
Authors: Zhang Mengjiao , Niu Jiechao , Xu Mengmeng , Wei Erhu , Liu Peng , Sheng Guangyao 
Published: February 2024

BackgroundPompe disease (PD) is a rare, progressive autosomal recessive lysosomal storage disorder that directly impacts mitochondrial function, leading to structural abnormalities and potentially culminating in heart failure or cardiogenic shock. The clinical course and molecular mechanisms of the disease remain incompletely understood.MethodsWe performed a retrospective analysis to examine the clinical manifestations, genetic traits, and the relationship between PD and mitochondrial function in a pediatric patient. This comprehensive evaluation included the use of ultrasound echocardiograms, computed tomography (CT) scans, electrocardiograms, mutagenesis analysis, and structural analysis to gain insights into the patient's condition and the underlying mechanisms of PD. For structural analysis and visualization, the structure of protein data bank ID 5KZX of human GAA was used, and VMD software was used for visualization and analysis.ResultsThe study revealed that a 5-month-old male infant was admitted due to fever, with physical examination finding abnormal cardiopulmonary function and hepatomegaly. Laboratory tests and echocardiography confirmed heart failure and hypertrophic cardiomyopathy. Despite a week of treatment, which normalized body temperature and reduced pulmonary inflammation, cardiac abnormalities did not show significant improvement. Further genetic testing identified a homozygous mutation c.2662G&gt;T (p.E888) in the GAA gene, leading to a diagnosis of Infantile-Onset Pompe Disease (IOPD).ConclusionsAlthough enzyme replacement therapy can significantly improve the quality of life for patients with PD, enhancing mitochondrial function may represent a new therapeutic strategy for treating PD.
Prevalence and clinical correlates of hyperhomocysteinemia in Chinese urban population with hypertension
Authors: Xu Yayun , Feng Haixing , Zhang Liping , Li Yanlei , Chi Feng , Ren Lijie 
Published: February 2024

ContextThe coexistence of hypertension and elevated homocysteine (Hcy) levels has a mutually reinforcing impact on the susceptibility to cardio-cerebrovascular disease.ObjectiveThe aim was to assess the prevalence, clinical correlation, and demographic characteristics of hyperhomocysteinemia (HHcy) within the Chinese urban population with hypertension.MethodsA cohort of 473 individuals with hypertension were selected from four communities in Shenzhen, China. Demographic attributes, clinical profiles, and lifestyle behaviors were gathered and compared between individuals with and without HHcy. A logistic regression model was employed to examine potential factors associated with the prevalence of HHcy. Correlation between Hcy levels and clinical characteristics was assessed through multiple linear regression analysis.ResultsThe prevalence of HHcy in the population with hypertension was 31.3%. In comparison to individuals without HHcy, those with HHcy exhibited a higher proportion of males, a higher prevalence of smoking and alcohol consumption, and a higher proportion of cases with the homozygous (TT) genotype at the MTHFR C677T polymorphism. Moreover, individuals with HHcy had lower levels of folic acid (FA), and lower fruit and vitamin B12 intake. Furthermore, the risk factors for HHcy were male (B = 1.430, OR = 4.179) and MTHFR (TT) (B = 1.086, OR = 2.961). In addition, the multiple linear regression analysis revealed a significant association between Hcy levels and gender (B = -2.784, P = 0.004), MTHFR genotypes (B = 1.410, P = 0.005), and FA levels (B = -0.136, P = 0.030).ConclusionThe high prevalence of HHcy among hypertensive patients in this Chinese urban population underscores the necessity for interventions targeting modifiable risk factors such as dietary choices and lifestyle practices.
China contributed to low-carbon development: carbon emission increased but carbon intensity decreased
Authors: Huang Chunbo , Gan Xintao , Wan Yunshan , Jin Lin , Teng Jiaxi , Li Zeyu 
Published: February 2024

IntroductionPopulation expansion and economic development increased global greenhouse gas emissions, leading to serious environmental degradation. China, the world's largest developing country and promoter of the “Belt and Road Initiative” (BRI), accounts for 28.8% of the world"s total energy carbon emissions. How to reduce energy consumption to achieve the “double carbon” target (i.e., carbon peaking and carbon neutrality) and promote the implementation of Green BRI is still a serious challenge that China needs to face. MethodsWe evaluated China's carbon emissions using three indicators (i.e., total carbon emission, carbon intensity, and carbon emissions effect), and used spatial analysis to reveal the spatial and temporal trends of China's carbon emissions. In addition, the LMDI model was adopted to explore the driving mechanism of carbon emissions, so as to seek a path that can achieve harmonious economic and environmental development, as well as the “double carbon” target.ResultsChina's total carbon emission increased at a rate of 226.12% from 2000 to 2019, while the carbon intensity decreased at a rate of 48.84%. Carbon emission showed a trend of increasing and then decreasing from southwest to northeast. From 2000 to 2019, the total carbon emission, Gross Domestic Product (GDP), population size and total energy consumption are growing in synergy. Economic and population effects are positively related to carbon emissions, while technology effects are negatively related to it, indicating technological innovations contribute to the reduction of carbon emissions.DiscussionSome suggestions were proposed to control carbon emissions with a view to helping policy makers to formulate relevant policies. The findings provide a scientific basis and reference for the country to achieve the “double carbon” target and the low-carbon sustainable development of BRI.
Response of serum biochemical profile, antioxidant enzymes, and gut microbiota to dietary Hong-bailanshen supplementation in horses
Authors: Ding Jinxue , Gu Bolin , Meng Jinwu , Hu Mengxin , Wang Wenjia , Liu Jiaguo 
Published: February 2024

BackgroundTraditional Chinese medicine (TCM) is widely used in humans and animals, which is very important for health. TCM affects the body ‘s immunity and changes in intestinal flora. This study was conducted to investigate the effects of dietary Hong-bailanshen (HBLS) supplementation in horses on serum biochemical profile, antioxidant enzymes and gut microbiota.MethodsIn this study, five horses were selected. On day 0, 14, 28, blood samples and feces were collected on days 0, 14, and 28 to analyse gut microbiota, serum biochemical and redox indexes.ResultsThe results showed that the addition of HBLS to horse diets significantly decreased the level of alanine aminotransferase, alkaline phosphatase, creatine kinase and malondialdehyde (p &lt; 0.05, p &lt; 0.01) and significantly increased the activity of total antioxidant capacity, superoxide dismutase and catalase (p  &lt; 0.05, p  &lt; 0.01). Compared with day 14, the levels of alanine aminotransferase, alkaline phosphatase and creatine kinase were significantly decreased; however, the level of catalase was significantly increased in the horses continuously fed with HBLS for 28 days (p  &lt; 0.05, p &lt; 0.01). Alpha diversity analysis was performed that chao1 (p  &lt; 0.05), observed_specicies, faith’pd and goods_coverage upregulated in the horses fed HBLS. A total of 24 differential genera were detected adding HBLS to diet increased the abundance of Bacillus, Lactobacillaceae, Leuconostocaceae, Christensenellaceae, Peptostreptococcaceae, Faecalibacterium, Erysipelotrichaceae, Pyramidobacter, Sphaerochaeta, WCHB1-25, Bacteria, Oscillospira, and Acetobacteraceae, while reduced Aerococcus, EtOH8, Syntrophomonas, Caulobacter, Bradyrhizobiaceae, W22, Succinivibrionaceae, and Desulfovibrio (p &lt; 0.05, p &lt; 0.01).ConclusionAdding HBLS to the diet could be a potentially effective strategy to improve horses’ health.
Advancements in LAM-based diagnostic kit for tuberculosis detection: enhancing TB diagnosis in HIV-negative individuals
Authors: Gao Man , Wu Qianhong , Wang Xinhong , Sun Xiuli , Li Meng , Bai Guanghong 
Published: February 2024

ObjectiveThe purpose of this study was to investigate the diagnostic value of urine lipoarabinomannan (LAM) detection based on chemiluminescence assay for pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) in HIV-negative individuals.MethodsA total of 215 patients and 37 healthy individuals were included according to inclusion and exclusion criteria, including 173 cases of PTB and 42 cases of EPTB. Sputum smears, sputum culture, TB-RNA, GeneXpert, and urine LAM results were obtained from all patients before treatment. Using the composite reference standard as the reference, the diagnostic performance of these methods for PTB and EPTB was evaluated, and the diagnostic performance and cost-effectiveness of different combinations were analyzed.ResultsIn PTB, LAM exhibited the highest sensitivity (55.49%), followed by GeneXpert (44.51%). In EPTB, LAM also had the highest sensitivity (40.48%), followed by GeneXpert (33.33%). When combined with one method, LAM combined with GeneXpert showed the highest sensitivity for both PTB (68.79%) and EPTB (61.9%). When combined with two methods, culture, GeneXpert, and LAM showed the highest sensitivity for both PTB (73.99%) and EPTB (69.05%). In terms of cost-effectiveness analysis, the price of LAM was significantly lower than that of GeneXpert ($129.82 vs. $275.79 in PTB and 275.79 vs. 502.33 in EPTB). Among all combinations, the combination of LAM and sputum smear had the lowest cost, with prices of $124.94 for PTB and $263.72 for EPTB.ConclusionUrine LAM detection based on chemiluminescence assay can be used as an adjunct diagnostic tool for PTB and EPTB in HIV-negative individuals. This facilitates expanding the current application of urine LAM from solely HIV-positive populations to the general population. LAM detection can overcome the limitations of obtaining clinical samples, and its ease of sample acquisition will be beneficial for its broader application in a larger scope. For economically better-off areas, we recommend using a combination of LAM + GeneXpert+culture for higher sensitivity; for economically disadvantaged areas, LAM + smear microscopy combination can provide a quick and accurate diagnosis of tuberculosis at a lower cost.
Sex-driven variability in TSPO-expressing microglia in MS patients and healthy individuals
Authors: Laaksonen Sini , Saraste Maija , Nylund Marjo , Hinz Rainer , Snellman Anniina , Rinne Juha , Matilainen Markus , Airas Laura 
Published: February 2024

BackgroundMales with multiple sclerosis (MS) have a higher risk for disability progression than females, but the reasons for this are unclear.ObjectiveWe hypothesized that potential differences in TSPO-expressing microglia between female and male MS patients could contribute to sex differences in clinical disease progression.MethodsThe study cohort consisted of 102 MS patients (mean (SD) age 45.3 (9.7) years, median (IQR) disease duration 12.1 (7.0–17.2) years, 72% females, 74% relapsing–remitting MS) and 76 age- and sex-matched healthy controls. TSPO-expressing microglia were measured using the TSPO-binding radioligand [11C](R)-PK11195 and brain positron emission tomography (PET). TSPO-binding was quantified as distribution volume ratio (DVR) in normal-appearing white matter (NAWM), thalamus, whole brain and cortical gray matter (cGM).ResultsMale MS patients had higher DVRs compared to female patients in the whole brain [1.22 (0.04) vs. 1.20 (0.02), p = 0.002], NAWM [1.24 (0.06) vs. 1.21 (0.05), p = 0.006], thalamus [1.37 (0.08) vs. 1.32 (0.02), p = 0.008] and cGM [1.25 (0.04) vs. 1.23 (0.04), p = 0.028]. Similarly, healthy men had higher DVRs compared to healthy women except for cGM. Of the studied subgroups, secondary progressive male MS patients had the highest DVRs in all regions, while female controls had the lowest DVRs.ConclusionWe observed higher TSPO-binding in males compared to females among people with MS and in healthy individuals. This sex-driven inherent variability in TSPO-expressing microglia may predispose male MS patients to greater likelihood of disease progression.
Blood urea nitrogen to serum albumin ratio is associated with all-cause mortality in patients with AKI: a cohort study
Authors: Shi Yue , Duan Hangyu , Liu Jing , Shi Xiujie , Zhang Yifan , Zhang Qi , Zhao Mingming , Zhang Yu 
Published: February 2024

BackgroundThis study aims to investigate the relationship between blood urea nitrogen to serum albumin ratio (BAR) and all-cause mortality in patients with acute kidney injury (AKI) and evaluate the effect of BAR on the prognosis of AKI.MethodsAdult patients with AKI admitted to the ICU in the Medical Information Mart for Intensive Care IV (MIMIC-IV) were selected in a retrospective cohort study. BAR (mg/g) was calculated using initial blood urea nitrogen (mg/dl)/serum albumin (g/dl). According to the BAR, these patients were divided into quartiles (Q1–Q4). Kaplan–Meier analysis was used to compare the mortality of the above four groups. Multivariate Cox regression analysis was used to evaluate the association between BAR and 28-day mortality and 365-day mortality. The receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated, and the subgroup analysis was finally stratified by relevant covariates.ResultsA total of 12,125 patients with AKI were included in this study. The 28-day and 365-day mortality rates were 23.89 and 39.07%, respectively. Kaplan–Meier analysis showed a significant increase in all-cause mortality in patients with high BAR (Log-rank p &lt; 0.001). Multivariate Cox regression analysis showed that BAR was an independent risk factor for 28-day mortality (4.32 &lt; BAR≤7.14: HR 1.12, 95% CI 0.97–1.30, p = 0.114; 7.14 &lt; BAR≤13.03: HR 1.51, 95% CI 1.31–1.75, p &lt; 0.001; BAR&gt;13.03: HR 2.07, 95% CI 1.74–2.47, p &lt; 0.001; Reference BAR≤4.32) and 365-day mortality (4.32 &lt; BAR≤7.14: HR 1.22, 95% CI 1.09–1.36, p &lt; 0.001; 7.14 &lt; BAR≤13.03: HR 1.63, 95% CI 1.46–1.82, p &lt; 0.001; BAR&gt;13.03: HR 2.22, 95% CI 1.93–2.54, p &lt; 0.001; Reference BAR ≤ 4.32) in patients with AKI. The AUC of BAR for predicting 28-day mortality and 365-day mortality was 0.649 and 0.662, respectively, which is better than that of blood urea nitrogen and sequential organ failure assessment. In addition, subgroup analysis showed a stable relationship between BAR and adverse outcomes in patients with AKI.ConclusionBAR is significantly associated with increased all-cause mortality in patients with AKI. This finding suggests that BAR may help identify people with AKI at high risk of mortality.
Geographical and temporal differences in gastric and oesophageal cancer registration by subsite and morphology in Europe
Authors: Giusti Francesco , Martos Carmen , Bettio Manola , Negrão Carvalho Raquel , Zorzi Manuel , Guzzinati Stefano , Rugge Massimo 
Published: February 2024

BackgroundGastric and oesophageal cancers pose a serious public health concern. In 2020 a total of 189,031 incident cases (136,038 stomach, 52,993 oesophagus) and 142,508 deaths (96,997 stomach, 45,511 oesophagus) were estimated in Europe. Oesophago-gastric cancers are a heterogeneous disease, with different aetiology and epidemiology for the various topographic subsites and main histopathological types. Topography subsite and morphology is key information to allow differentiating oesophago-gastric cancers. Correct registration and coding of such variables are fundamental in allowing proper description of the epidemiology of different subsites and histopathological types of oesophago-gastric cancers. The aim of this article is to highlight geographical and temporal variability in topography and morphology of oesophago-gastric cancers observed in Europe in the considered period.MethodsData collected in the framework of the ENCR-JRC (European Commission’s Joint Research Centre) data call and feeding the European Cancer Information System (ECIS) were used to assess the variability of topography and morphology registration of gastric and oesophageal cancer in Europe in the period 1995-2014. Malignant cancers of the stomach and the oesophagus were selected following, respectively, topography codes C16 and C15 of the International Classification of Diseases for Oncology, third edition (ICD-O-3). Analyses were performed by subsite, morphology group, year, sex, and European region.ResultsA total of 840,464 incident cases occurring in the period 1995-2014 – 579,264 gastric (67.2%) and 276,260 (32.8%) oesophageal carcinomas – was selected for the analysis. Data was recorded by 53 PBCRs (9 based in Northern Europe, 14 in Western Europe, 3 in Eastern Europe and 27 in Southern Europe) from 19 countries.ConclusionA wide variability in oesophago-gastric cancers topographic subsites and histopathological types patterns was observed, with a corresponding improvement in accuracy of registration in the analysis period. PBCRs are ideally placed to guide the epidemiological evaluations of such a complex group of diseases, in collaboration with clinicians, patients and other public health stakeholders.
Prospective study investigating hypofractionated proton beam therapy in patients with inoperable early stage non-small cell lung cancer
Authors: Yang Kyungmi , Noh Jae Myoung , Park Hye Yun , Yoo Hongseok , Shin Sun Hye , Pyo Hongryull 
Published: February 2024

PurposeTo report the results of hypofractionated proton beam therapy (PBT) for the treatment of early stage lung cancer in patients not suitable for surgical resection.MethodsData from 27 adult patients, who were diagnosed with inoperable cT1-3N0 non-small cell lung cancer (NSCLC) between March 2018 and August 2020, were analyzed. PBT was prescribed as 64 Cobalt Grey equivalents delivered in 8 fractions (Sumitomo, Japan). The primary endpoint was local control; secondary endpoints included overall survival, quality of life, and grade ≥3 toxicity.ResultsThe median follow-up was 28.9 months (range, 1.1–62.1 months). During follow-up, 13 (48.1%) patients experienced disease progression, including local progression in 7. Two-year local control rates were 73.5%, 85.7% for T1, and 61.4% for T2-3. The worse local control rate was observed in those with large clinical target volumes (≥ 47.5 cc) and heavy smoking history (≥30 pack-years). The two-year overall survival rate was 76.5%. Grade 3 radiation-related toxicities were observed in 2 (7.4%) patients. In the European Organization for Research and Treatment of Cancer Quality of Life Core 30 results, the global score did not change significantly from baseline. However, dyspnea score increased from 19.8 before PBT to 33.3 at 4 months’ post-PBT (p=0.047) and was maintained until 13 months (p=0.028).ConclusionHypofractionated PBT was a safe treatment option for inoperable early stage NSCLC and appeared to be appropriate for small tumor volumes. However, local control for larger tumors requires further improvement.