bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness analysis of gemtuzumab ozogamicin for the treatment of de novo CD33-positive Acute Myeloid Leukaemia (AML) in Italy
Authors: Cairoli Roberto , Furneri Gianluca , Di Virgilio Roberto , Veggia Barbara , Ferrara Felicetto 
Published: January 2023

Abstract
Background
Based on the results from the ALFA-0701 study, gemtuzumab ozogamicin (GO) has been approved by the European Medicine Agency and by the Italian Drug Agency for the first line treatment of de novo acute-myeloid leukemia (AML). In this analysis, we assessed the cost-effectiveness of GO in combination with daunorubicin and cytarabine (DA), vs DA alone, adopting the perspective of the Italian National Health Service.

Methods
For this analysis, a cohort state transition model was developed. The model was designed to capture health states and events that occur throughout the entire disease course and that impact costs and outcomes. The ALFA-0701 study was the main source of clinical data for this analysis. In the model, patients had the same baseline characteristics and experienced the same clinical improvements as in the ALFA-0701 study. Economic data (resource consumption and unit costs) were adapted to reflect expenditure for the Italian National Health Service. Utilities per health state and disutilities due to adverse events were based on the literature and on the general population for those functionally cured. A lifetime horizon was adopted, with both costs and outcome being discounted of 3.0%, annually. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of results.

Results
In the base case (lifetime horizon; primary source of data: study ALFA-0701; perspective: Italian National Health Service; discount rate on costs and outcomes: 3.0%), GO + DA was more effective DA both in terms of life-year (LY) survival (6.42 LY vs 5.75 LY, respectively) and quality-of-life adjusted survival (4.69 QALY vs 4.19 QALY, respectively). The overall costs were almost similar in the two groups (slightly lower with GO + DA than with DA; €162,424 and €162,708, respectively). The use of GO increased the costs of drug therapy but saved costs of relapse and costs associated with transplantation (HSCT).

Conclusions
If results of the ALFA-0701 study are applied to the Italian healthcare environment, then gemtuzumab ozogamicin, in combination with daunorubicin and cytarabine, would clinical outcomes and reduce lifetime costs, compared with daunorubicin and cytarabine alone for the first line treatment of de novo AML.

Trial registration
Not applicable.
Occurrence of variants of unknown clinical significance in genetic testing for hereditary breast and ovarian cancer syndrome and Lynch syndrome: a literature review and analytical observational retrospective cohort study
Authors: Adam Felicia , Fluri Muriel , Scherz Amina , Rabaglio Manuela 
Published: January 2023

Abstract
Background and purpose
Over the last decade, the implementation of multigene panels for hereditary tumor syndrome has increased at our institution (Inselspital, University Hospital Berne, Switzerland). The aim of this study was to determine the prevalence of variants of unknown significance (VUS) in patients with suspected Lynch syndrome and suspected hereditary breast and ovarian cancer syndrome, the latter in connection with the trend toward ordering larger gene panels.

Results
Retrospectively collected data from 1057 patients at our institution showed at least one VUS in 126 different cases (11.9%). In patients undergoing genetic testing for BRCA1/2, the prevalence of VUS was 6%. When < 10 additional genes were tested in addition to BRCA1/2, the prevalence increased to 13.8%, and 31.8% for > 10 additional genes, respectively. The gene most frequently affected with a VUS was ATM. 6% of our patients who were tested for Lynch syndrome had a VUS result in either MLH1, MSH2 or MSH6.

Conclusions
Our data demonstrate that panel testing statistically significantly increases VUS rates due to variants in non-BRCA genes. Good genetic counseling before and after obtaining results is therefore particularly important when conducting multigene panels to minimize patient uncertainty due to VUS results.
Expression of glycerol-3-phosphate acyltransferase increases non-polar lipid accumulation in Nannochloropsis oceanica
Authors: Südfeld Christian , Kiyani Aamna , Wefelmeier Katrin , Wijffels René H. , Barbosa Maria J. , D’Adamo Sarah 
Published: January 2023

AbstractMicroalgae are considered a suitable production platform for high-value lipids and oleochemicals. Several species including Nannochloropsis oceanica produce large amounts of essential $$\omega$$
ω
-3 polyunsaturated fatty acids (PUFAs) which are integral components of food and feed and have been associated with health-promoting effects. N. oceanica can further accumulate high contents of non-polar lipids with chemical properties that render them a potential replacement for plant oils such as palm oil. However, biomass and lipid productivities obtained with microalgae need to be improved to reach commercial feasibility. Genetic engineering can improve biomass and lipid productivities, for instance by increasing carbon flux to lipids. Here, we report the overexpression of glycerol-3-phosphate acyltransferase (GPAT) in N. oceanica during favorable growth conditions as a strategy to increase non-polar lipid content. Transformants overproducing either an endogenous (NoGPAT) or a heterologous (Acutodesmus obliquus GPAT) GPAT enzyme targeted to the endoplasmic reticulum had up to 42% and 51% increased non-polar lipid contents, respectively, compared to the wild type. Biomass productivities of transformant strains were not substantially impaired, resulting in lipid productivities that were increased by up to 37% and 42% for NoGPAT and AoGPAT transformants, respectively. When exposed to nutrient stress, transformants and wild type had similar lipid contents, suggesting that GPAT enzyme exerts strong flux control on lipid synthesis in N. oceanica under favorable growth conditions. NoGPAT transformants further accumulated PUFAs in non-polar lipids, reaching a total of 6.8% PUFAs per biomass, an increase of 24% relative to the wild type. Overall, our results indicate that GPAT is an interesting target for engineering of lipid metabolism in microalgae, in order to improve non-polar lipid and PUFAs accumulation in microalgae.
Aspirin increases chemosensitivity of colorectal cancer cells and inhibits the expression of toll-like receptor 4
Authors: Ying Jun , Zhou Haiyang , Wang Zhiguo , You Qing , Chen Junnan , Lu Hao , Zhang Jian 
Published: January 2023

Abstract
Background
Chemotherapy resistance is an important bottleneck affecting the efficacy of chemotherapy in colon cancer. Therefore, improving the chemotherapy sensitivity of colorectal cancer cells is of great significance for improving the prognosis of patients with colon cancer.

Methods
CCK-8 assay was employed to examine the cell viability of colorectal cancer cell lines. Realtime-PCR and western blot were used to explore toll-like receptor 4 (TLR4) expression in colorectal cancer cell lines. The functions of TLR4 in the stemness of the colorectal cancer cell lines were analyzed by infecting cells with lentivirus containing TLR4 siRNA.

Results
We found that aspirin could effectively enhance the chemosensitivity of CT26 and HCT116 colorectal cancer cell lines. Aspirin can also inhibit the stemness of colorectal cancer cell including inhibiting the number of clone formation and reducing the volume and number of cell spheres and inducing the down-regulation of stemness-related genes. Besides that, aspirin also lead to down-regulation of TLR4 expression in colorectal cancer cells. The TLR4 positive colorectal cancer cells demonstrated a higher chemotherapy resistance potential than TLR4 negative colorectal cancer cells. In addition, the stemness of TLR4 positive colorectal cancer cells is stronger than TLR4 negative colorectal cancer cells.

Conclusion
The results of our study indicate that aspirin increases chemosensitivity of colorectal cancer cells and inhibits the expression of toll-like receptor 4.
Erythrocyte membrane with CLIPPKF as biomimetic nanodecoy traps merozoites and attaches to infected red blood cells to prevent Plasmodium infection
Authors: He Zhouqing , Yu Chuyi , Pan Ziyi , Li Xiaobo , Zhang Xiangxiang , Huang Qijing , Liao Xingcheng , Hu Jiaoting , Zeng Feng , Ru Li , Yu Wanlin , Xu Qin , Song Jianping , Liang Jianming 
Published: January 2023

Abstract
Background
Malaria remains a serious threat to global public health. With poor efficacies of vaccines and the emergence of drug resistance, novel strategies to control malaria are urgently needed.

Results
We developed erythrocyte membrane-camouflaged nanoparticles loaded with artemether based on the growth characteristics of Plasmodium. The nanoparticles could capture the merozoites to inhibit them from repeatedly infecting normal erythrocytes, owing to the interactions between merozoites and heparin-like molecules on the erythrocyte membrane. Modification with a phosphatidylserine-targeting peptide (CLIPPKF) improved the drug accumulation in infected red blood cells (iRBCs) from the externalized phosphatidylserine induced by Plasmodium infection. In Plasmodium berghei ANKA strain (pbANKA)-infected C57BL/6 mice, the nanoparticles significantly attenuated Plasmodium-induced inflammation, apoptosis, and anemia. We observed reduced weight variation and prolonged survival time in pbANKA-challenged mice, and the nanoparticles showed good biocompatibility and negligible cytotoxicity.

Conclusion
Erythrocyte membrane-camouflaged nanoparticles loaded with artemether were shown to provide safe and effective protection against Plasmodium infection.

Graphical Abstract
Internal jugular vein reconstruction using a triple-paneled great saphenous vein graft
Authors: Miyamoto Shimpei , Hidaka Takeaki , Fukuoka Osamu , Fujisawa Kou , Okazaki Mutusmi 
Published: January 2023

Abstract
Background
Donor–recipient diameter discrepancy can be problematic when using an autologous great saphenous vein graft for internal jugular vein reconstruction. A triple-paneled method of saphenous vein grafting is one solution.

Case presentation
A 54-year-old man with a thyroid papillary carcinoma underwent total thyroidectomy and bilateral neck dissection. An 8-cm segment of the right internal jugular vein was resected. For reconstruction, a 30-cm segment of the great saphenous vein was harvested and divided into three pieces of equal length. After opening each piece longitudinally, they were sutured together in a side-by-side fashion to create a cylinder that was used to reconstruct the internal jugular vein defect. The graft was patent 10 months after the surgery.

Conclusion
The triple-paneled method is feasible for autologous great saphenous vein graft reconstruction of the internal jugular vein.
Improving institutional platforms for evidence-informed decision-making: getting beyond technical solutions
Authors: Mecaskey Jeffrey , Verboom Ben , Liverani Marco , Mijumbi-Deve Rhona , Jessani Nasreen S. 
Published: January 2023

AbstractPurely technical interventions aimed at enhancing evidence-informed decision-making (EIDM) have rarely translated into organizational institutionalization or systems change. A panel of four presentations at the Health Systems Global 2020 conference provides a basis for inference about contextual factors that influence the establishment and sustainability of institutional platforms to support EIDM. These cases include local structures such as citizen panels in Uganda, regional knowledge translation structures such as the West African Health Organization, global multilateral initiatives such as the “One Health” Quadrapartite and regional public health networks in South-East Asia. They point to the importance of political economy as well as technical capability determinants of evidence uptake and utilization at institutional, organizational and individual levels. The cases also lend support to evidence that third-party (broker and intermediary) supportive institutions can facilitate EIDM processes. The involvement of third-party supranational organizations, however, poses challenges in terms of legitimacy and accountability.
Systematic review of economic evaluations on stereotactic ablative radiotherapy (SABR) compared to other radiotherapy techniques or surgical procedures for early-stage non-small cell lung cancer
Authors: Maia Fernando Henrique de Albuquerque , Rozman Luciana Martins , Carvalho Heloisa de Andrade , de Soárez Patrícia Coelho 
Published: January 2023

Abstract
Background
Stereotactic ablative radiotherapy (SABR) is recommended as first-choice treatment to inoperable early-stage non-small cell lung cancer (NSCLC). However, it is not widely adopted in developing countries, and its cost-effectiveness is unclear. We aimed to perform a systematic review of full economic evaluations (EE) that compared SABR with other radiotherapy or surgical procedures to assess the results and methodological approach.

Methods
The protocol was registered on PROSPERO (CRD42021241640). We included full EE studies with early-stage NSCLC in which one group was submitted to SABR. Studies that were partial EE, included advanced NSCLC or other neoplasm were excluded. We performed the last search on June 2021 in Medline, EMBASE and other databases. The reporting quality were assessed by CHEERS checklist. The main characteristics of each study were tabulated, and the results were presented by a narrative synthesis.

Results
We included nine studies. Three compared radiotherapy techniques, in which SABR was found to be dominant or cost-effective. Six compared SABR with surgery, and in this group, there was not a unanimous decision. All included only direct healthcare costs but varied about categories included. The parameters used in the model-based studies were highly heterogeneous using mixed data from various sources. The items properly reported varied from 29 to 67%.

Conclusions
The studies were all from developed countries and lacked in reporting quality. We recommend that developing countries produce their own studies. More strict alignment to reporting guidelines and use of robust evidence as model parameters are also advised.
Direct and indirect medical costs of bladder cancer in Iran
Authors: Raadabadi Mehdi , Daroudi Rajabali , Zendehdel Kazem , Haghdoost Ali Akbar , Ebadzadeh Mohammad Reza , Rashidian Hamideh 
Published: January 2023

Abstract
Background
Bladder cancer is one of the most prevalent and costly cancers in the world. Estimating the economic burden of bladder cancer is essential for allocating resources to different sectors of health systems and determining the appropriate payment mechanisms. The present study aimed at estimating the economic burden of bladder cancer in Iran.

Methods
In this study, we used a prevalence-based approach for estimating the economic burden of bladder cancer. Direct and indirect costs of bladder cancer were calculated using the cost of illness and human capital approaches. Data were collected using a researcher-made checklist obtained from several sources including Iran bladder cancer clinical practice guideline, the Statistical Center of Iran, Iran’s Ministry of Cooperatives, Labor, and Social Welfare, Relative Value of Health Services (RVHS) book and Iranian Food and Drug Administration organization.
The analyses were done by Microsoft Excel 2013 and Stata 13.

Results
The number of the cases of 5-year prevalence of bladder cancer in Iran was estimated as 21,807 people in 2018. The economic burden of bladder cancer in Iran was estimated at US$ 86,695,474. Indirect medical costs constituted about two-third of the economic burden of bladder cancer, and mostly related to productivity loss due to mortality. Most of the direct medical costs (29.7%) were related to the stage T2–T3 and transurethral resection of bladder (31.01%) and radical cystectomy (19.99%) procedures.

Conclusion
Our results showed that the costs of bladder cancer, imposed on the healthcare system, were significant and mostly related to lost production costs. The implementation of screening and diagnostic programs can improve the survival rate and quality of life of patients and reduce the cost of lost productivity due to mortality in these patients.
One-stage vs two-stage bilateral THA in Lombardy: a cost-effectiveness analysis
Authors: Pironti Pierluigi , Ambrosanio Andrea , Vismara Valeria , Viganò Marco , Bucci Eugenia , Sirtori Paolo , Peretti Giuseppe M , Mangiavini Laura 
Published: January 2023

Abstract
Background
Total hip arthroplasty (THA) is the most common treatment for primary and secondary end-stage hip osteoarthritis (OA). Almost 20% of all patients undergoing primary THA suffer from bilateral hip OA and, consequently, will need a contralateral procedure to be performed in the following years. The aim of this study is to evaluate the cost-effectiveness and the reliability of one-stage bilateral THA (1-BTHA) compared to two-stage bilateral THA (2-BTHA), in low-risk patients, performed with anterior minimally invasive surgery (AMIS).

Methods
Single patient’s costs were obtained by dividing the annual costs report by the number of hospitalizations, considering the diagnosis related group (DRG) of the two procedures. Then, 16 patients undergoing 1-BTHA and 8 undergoing 2-BTHA were examined. Hemoglobin (Hb) values before surgery and before discharge, transfusion rate and the occurrence of post-operative complications were observed.

Results
Procedural costs were divided in different subgroups: pre-hospitalization, operating room, hospital stay, post-operative follow-up and other costs. 1-BTHA total costs amount to 5.754,82€, while performing 2-BTHA costs 7.624,32€. However, considering DRG reimbursement, the hospital’s profit margin following 1-BTHA is lower than that following 2-BTHA (6.346,18€ versus 9.261,68€). Surgical time was found not to be significantly different between 1-BTHA and 2-BTHA (141,13 ± 26,1 min vs 164,8 ± 44,3 min; p = 0,111). The two groups showed a statistically significant difference in Hb decrease (4,8 ± 1,3 g/dl vs 3,3 ± 0,9; p = 0,001), despite no variances in transfusion rate. No further complications were observed in either group.

Conclusions
This study demonstrates how, in carefully selected patients, 1-BTHA performed with AMIS is a cost-effective and safe technique compared to 2-BTHA, resulting in a shorter OR time, LOS and lower overall costs.

Level of evidence
III
Supplementation with medium-chain fatty acids increases body weight loss during very low-calorie ketogenic diet: a retrospective analysis in a real-life setting
Authors: Vetrani Claudia , Verde Ludovica , Savastano Silvia , Colao Annamaria , Muscogiuri Giovanna , Barrea Luigi 
Published: January 2023

Abstract
Background
Very low-calorie ketogenic diet (VLCKD) has shown to significantly reduce body weight and fat mass, as well as inflammation. These effects are supported by nutritional ketosis, which triggers the utilization of the ketone body as an energy source. Medium-chain fatty acids (MCTs) might serve as potential enhancers of ketone bodies production with a greater effect on weight loss. Nevertheless, no clinical studies have evaluated the effect of MCTs supplementation in addition to VLCKD. Therefore, the present study aimed to evaluate whether the supplementation with MCTs can induce a greater weight reduction during the ketogenic phase of VLCKD.

Methods
In this retrospective study, 263 women with overweight/obesity (body mass index, BMI: 35.7 ± 5.3 kg/m2) aged 37.5 ± 14.2 years followed one of these dietary protocols for 45 days: (a) Control group, 83 participants (31.6%) (VLCKD without MCTs), (b) VLCKD + MCTs group, 86 participants (32.7%) (MCTs supplementation − 20 g/day- during VLCKD starting from the first day of the active phase), (c) VLCKD + earlyMCTs, 94 participants (35.7%) (MCTs supplementation − 20 g/day-starting from 5 days before the beginning of the VLCKD active phase. Anthropometric measures, body composition, and c-reactive protein (CRP) concentrations were collected at the beginning and at the end (45 days) of the VLCKD intervention.

Results
MCTs supplementation significantly decreased body weight, BMI, and waist circumference as compared to the control group, with a greater effect in the VLCKD + earlyMCTs group. A two-fold decrease in fat mass and an increase in muscle mass were observed in the VLCKD + earlyMCTs group as compared to the control group. As for inflammation, hs-CRP concentrations (assessed as absolute percent change) were significantly lower in the VLCKD + MCTs group (p = 0.009) and the VLCKD + earlyMCTs group (p = 0.011) than in the control group. A logistic regression model showed that VLCKD + earlyMCTs increase the likelihood of improvement of BMI classes (OR: 1.85, 95% CI 1.02–3.36) also after adjusting for the potential confounding factors.

Conclusion
MCTs supplementation (20 g/day) may be a useful tool to enhance the beneficial effect of VLCKD on the reduction of body weight and fat mass. In particular, MCTs supplementation before the beginning of the VLCKD active phase might facilitate ketosis thus contributing to the effectiveness of the nutritional intervention.
Medial–lateral versus lateral-only pinning fixation in children with displaced supracondylar humeral fractures: a meta-analysis of randomized controlled trials
Authors: Xing Binbin , Dong Bin , Che Xiaoling 
Published: January 2023

Abstract
Background
Supracondylar humeral fractures (SCHFs) are frequent in children, and closed reduction with percutaneous pin fixation remains the standard surgical treatment for displaced SCHFs. Two pinning configurations, medial–lateral crossed entry pinning (MLP) and lateral-only entry pinning (LP), are widely used, but which one is superior to another one is still debatable. This meta-analysis aimed to compare the efficacy and safety of both pinning fixation methods.

Methods
Randomized controlled trials (RCTs) were searched on PubMed, EMBASE, Web of Science, Cochrane library and Google Scholar. Relative risk (RR) and mean difference (MD) with corresponding 95% confidence interval (CI) were calculated for radiographical outcomes, functional outcomes and complications.

Results
A total of 19 RCTs comprising 1297 Gartland type II and type III fractures were included. MLP had a decreased risk of loss of reduction (RR = 0.70, 95%CI 0.52–0.94, P = 0.018) but a higher risk of iatrogenic ulnar nerve injury (RR = 2.21, 95%CI 1.11–4.41, P = 0.024) than LP. However, no significant difference was observed for incidence of ulnar nerve injury if applying a mini-open technique in MLP group (RR = 1.73, 0.47–6.31, P = 0.407). There were no differences between both groups in loss of carrying angle (MD = − 0.12, 95%CI − 0.39 to 0.16), loss of Baumann angle (MD = 0.08, 95%CI − 0.15 to 0.30), excellent grading of Flynn criteria (RR = 1.06, 95%CI 0.99–1.14, P = 0.102) and pin tract infection (RR = 0.92, 95%CI 0.50–1.70).

Conclusions
MLP is more effective in maintaining fixation, while LP is safer with respect to ulnar nerve injury. MLP with a mini-open technique reduces the risk of ulnar nerve lesion and is an effective and safe choice.