bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sponsorship bias in published pharmacoeconomic evaluations of national reimbursement negotiation drugs in China: a systematic review
Authors: He Zixuan , Huang Xianqin , Chen Dingyi , Wang Guoan , Zhu Yuezhen , Li Huangqianyu , Han Sheng , Shi Luwen , Guan Xiaodong 
Published: November 2023

BackgroundChina’s National Reimbursement Drug List (NRDL) has become the primary route for drug reimbursement in China. More recently, the authority has made pharmacoeconomic evaluation an integral part of the application for NRDL inclusion. The underlying financial conflict of interests (FCOI) of pharmacoeconomic evaluations, however, has the potential to influence evidence generated and thus subsequent decision-making yet remains poorly understood.MethodsWe searched for studies published between January 2012 and January 2022 on the 174 drugs added to the 2017–2020 NRDLs after successful negotiation. We categorised the study’s FCOI status into no funding, industry funding, non-profit funding and multiple fundings based on authors’ disclosure and assessed the reporting quality of included studies using the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. We compiled descriptive statistics of funding types and study outcomes using t-tests and χ2tests and conducted multivariate regression analysis.ResultsWe identified 378 records and our final sample included 92 pharmacoeconomic evaluations, among which 69.6% were conducted with at least one funding source. More than half (57.6%) of the evaluations reached favourable conclusions towards the intervention drug and 12.6% reached a dominant result of the intervention drug over the comparison from model simulation. The reporting quality of included studies ranged from 19 to 25 (on a scale of 28), with an average of 22.3. The statistical tests indicated that industry-funded studies were significantly more likely to conclude that the intervention therapy was economical (p<0.01) and had a significantly higher proportion of resulting target drug economically dominated the comparison drug (p<0.05).ConclusionThe study revealed that FCOI bias is common in published pharmacoeconomic evaluations conducted in Chinese settings and could significantly influence the study’s economical results and conclusions through various mechanisms. Multifaceted efforts are needed to improve transparency, comparability and reporting standardisation.
Treatment of overweight and obesity in general practice: a cluster randomised trial
Authors: Nilsen Morten Dag , Mdala Ibrahimu , Werner Erik L 
Published: November 2023

Overweight and obesity are among the most serious health problems of our time.A majority of patients with overweight and obesity will first get in touch with health services through primary care. This makes it crucial to develop strategies to enable physicians in primary care to help and treat patients with overweight and obesity. The physicians tend to avoid this subject. The main reason is reported to be lack of knowledge and education, and that they have nothing concrete to offer their patients.We wanted to examine if a simple method with specific measures could be used in Norwegian general practice and achieve meaningful weight loss.23 physicians and 210 patients participated in the study.The physicians who participated were cluster randomised into either control group or intervention group. The physicians in the control group were told to follow their usual approach, while the physicians in the intervention group followed a fixed plan with specific diets given orally and in writing to the patients. The inclusion criteria for both groups were: body mass index (BMI)>30 kg/m2, or BMI>25 kg/m2with at least one weight-related condition. Weight was measured at the start, then after 1 year and finally after 2 years in both groups.We found no significant weight loss in the control group. In the intervention group, there was a weight loss of at least 10% by 25.5% after the first year and 24.2% after the entire observation period. 53.5% of the patients lost at least 5% of their weight in the first year and nearly 45% after the entire observation period. We conclude that a simple tool with a specific diet and activity plan is feasible in general practice and may produce significant weight loss. Trial registration number:NCT03000062.
Phase I/Ib, open-label, multicenter, dose-escalation study of the anti-TGF-β monoclonal antibody, NIS793, in combination with spartalizumab in adult patients with advanced tumors
Authors: Bauer Todd M , Santoro Armando , Lin Chia-Chi , Garrido-Laguna Ignacio , Joerger Markus , Greil Richard , Spreafico Anna , Yau Thomas , Goebeler Maria-Elisabeth , Hütter-Krönke Marie Luise , Perotti Antonella , Juif Pierre-Eric , Lu Darlene , Barys Louise , Cremasco Viviana , Pelletier Marc , Evans Helen , Fabre Claire , Doi Toshikiko 
Published: November 2023

BackgroundNIS793 is a human IgG2 monoclonal antibody that binds to transforming growth factor beta (TGF-β). This first-in-human study investigated NIS793 plus spartalizumab treatment in patients with advanced solid tumors.MethodsPatients received NIS793 (0.3–1 mg/kg every 3 weeks (Q3W)) monotherapy; following evaluation of two dose levels, dose escalation continued with NIS793 plus spartalizumab (NIS793 0.3–30 mg/kg Q3W and spartalizumab 300 mg Q3W or NIS793 20–30 mg/kg every 2 weeks [Q2W] and spartalizumab 400 mg every 4 weeks (Q4W)). In dose expansion, patients with non-small cell lung cancer (NSCLC) resistant to prior anti-programmed death ligand 1 or patients with microsatellite stable colorectal cancer (MSS-CRC) were treated at the recommended dose for expansion (RDE).ResultsSixty patients were treated in dose escalation, 11 with NIS793 monotherapy and 49 with NIS793 plus spartalizumab, and 60 patients were treated in dose expansion (MSS-CRC: n=40; NSCLC: n=20). No dose-limiting toxicities were observed. The RDE was established as NIS793 30 mg/kg (2100 mg) and spartalizumab 300 mg Q3W. Overall 54 (49.5%) patients experienced ≥1 treatment-related adverse event, most commonly rash (n=16; 13.3%), pruritus (n=10; 8.3%), and fatigue (n=9; 7.5%). Three partial responses were reported: one in renal cell carcinoma (NIS793 30 mg/kg Q2W plus spartalizumab 400 mg Q4W), and two in the MSS-CRC expansion cohort. Biomarker data showed evidence of target engagement through increased TGF-β/NIS793 complexes and depleted active TGF-β in peripheral blood. Gene expression analyses in tumor biopsies demonstrated decreased TGF-β target genes and signatures and increased immune signatures.ConclusionsIn patients with advanced solid tumors, proof of mechanism of NIS793 is supported by evidence of target engagement and TGF-β pathway inhibition.Trial registration numberNCT02947165.
TP53/mTORC1-mediated bidirectional regulation of PD-L1 modulates immune evasion in hepatocellular carcinoma
Authors: Yu Jiongjie , Ling Sunbin , Hong Jiachen , Zhang Lincheng , Zhou Wei , Yin Lu , Xu Shengjun , Que Qingyang , Wu Yongfeng , Zhan Qifan , Bao Jiaqi , Xu Nan , Liu Yuchen , Chen Kangchen , Wei Xuyong , Liu Zhikun , Feng Tingting , Zhou Lin , Xie Haiyang , Wang Shuai , Liu Jimin , Zheng Shusen , Xu Xiao 
Published: November 2023

BackgroundImmunotherapy has facilitated great breakthroughs in the treatment of hepatocellular carcinoma (HCC). However, the efficacy and response rate of immunotherapy are limited and vary among different patients with HCC. TP53 mutation substantially affects the expression of immune checkpoint molecules in multiple cancers. However, the regulatory relationship between programmed death ligand 1 (PD-L1) and TP53 is poorly studied in HCC. We aimed to elucidate the regulatory mechanism of PD-L1 in HCC with different TP53 statuses and to assess its role in modulating immune evasion in HCC.MethodsHCC mouse models and cell lines with different TP53 statuses were constructed. PD-L1 levels were detected by PCR, western blotting and flow cytometry. RNA-seqencing, immunoprecipitation, chromatin immunoprecipitation and transmission electron microscopy were used to elucidate the regulatory mechanism in HCC with different TP53 status. HCC mouse models and patient with HCC samples were analyzed to demonstrate the preclinical and clinical significance of the findings.ResultsWe report that loss of p53 promoted PD-L1 expression and reduced CD8+T-cell infiltration in patient with HCC samples and mouse models. Mammalian target of rapamycin (mTOR) pathway was activated in p53-loss-of-function HCC or after knocking down TP53. The transcription factor E2F1 was found to bind to the p53 protein in TP53 wild-type HCC cells, and inhibiting mammalian target of rapamycin complex 1 (mTORC1) disrupted this binding and enhanced E2F1 translocation to the nucleus, where it bound to the PD-L1 promoter and transcriptionally upregulated PD-L1. In p53-loss-of-function HCC cells, autophagosomes were activated after mTORC1 suppression, promoting the degradation of PD-L1 protein. The combination of mTOR inhibitor and anti-PD-L1 antibody enhanced CD8+T-cell infiltration and tumor suppression in TP53 wild-type HCC mouse models, but no benefit was observed in p53-loss-of-function HCC mouse models. In patients with TP53 wild-type HCC, PD-L1 levels were significantly higher in the high E2F1 group than in the low E2F1 group, and the low E2F1 level group had significantly superior survival.ConclusionWe revealed the bidirectional regulatory mechanism of PD-L1 mediated by TP53/mTORC1 in HCC. The combination of mTOR inhibitor and anti-PD-L1 antibody could be a novel precise immunotherapy scheme for TP53 wild-type HCC.
Neuromuscular and cardiovascular phenotypes in paediatric titinopathies: a multisite retrospective study
Authors: Meyer Alayne P , Barnett Cara L , Myers Katherine , Siskind Carly E , Moscarello Tia , Logan Rachel , Roggenbuck Jennifer , Rich Kelly A 
Published: November 2023

BackgroundPathogenic variants inTTNcause a spectrum of autosomal dominant and recessive cardiovascular, skeletal muscle and cardioskeletal disease with symptom onset across the lifespan. The aim of this study was to characterise the genotypes and phenotypes in a cohort ofTTN+paediatric patients.MethodsRetrospective chart review was performed at four academic medical centres. Patients with pathogenic or truncating variant(s) inTTNand paediatric-onset cardiovascular and/or neuromuscular disease were eligible.Results31 patients from 29 families were included. Seventeen patients had skeletal muscle disease, often with proximal weakness and joint contractures, with average symptom onset of 2.2 years. Creatine kinase levels were normal or mildly elevated; electrodiagnostic studies (9/11) and muscle biopsies (11/11) were myopathic. Variants were most commonly identified in the A-band (14/32) or I-band (13/32). Most variants were predicted to be frameshift truncating, nonsense or splice-site (25/32). Seventeen patients had cardiovascular disease (14 isolated cardiovascular, three cardioskeletal) with average symptom onset of 12.9 years. Twelve had dilated cardiomyopathy (four undergoing heart transplant), two presented with ventricular fibrillation arrest, one had restrictive cardiomyopathy and two had other types of arrhythmias. Variants commonly localised to the A-band (8/15) or I-band (6/15) and were predominately frameshift truncating, nonsense or splice-site (14/15).ConclusionOur cohort demonstrates the genotype–phenotype spectrum of paediatric-onset titinopathies identified in clinical practice and highlights the risk of life-threatening cardiovascular complications. We show the difficulties of obtaining a molecular diagnosis, particularly in neuromuscular patients, and bring awareness to the complexities of genetic counselling in this population.
COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune rheumatic Diseases (COVIAAD): safety, immunogenicity and antibody persistence at 12 months following Moderna Spikevax primary series
Authors: Colmegna Ines , Valerio Valeria , Amiable Nathalie , Useche Mariana , Rampakakis Emmanouil , Flamand Louis , Rollet-Labelle Emmanuelle , Bessette Louis , Fitzcharles Mary-Ann , Hazel Elizabeth , McCormack Deirdre , Michou Laëtitia , Panopalis Pantelis , Langlois Marc-André , Bernatsky Sasha , Fortin Paul R 
Published: November 2023

ObjectiveTo assess the safety, immunogenicity and cellular responses following the Moderna Spikevax primary series in rheumatic disease.MethodsWe conducted a 12-month, prospective, non-randomised, open-label, comparative trial of adults with either rheumatoid arthritis (RA, n=131) on stable treatment; systemic lupus erythematosus (SLE, n=23) on mycophenolate mofetil (MMF); other rheumatic diseases on prednisone ≥10 mg/day (n=8) or age-matched/sex-matched controls (healthy control, HC, n=58). Adverse events (AEs), humoral immune responses (immunogenicity: IgG positivity for anti-SARS-CoV-2 spike protein and its receptor binding domain, neutralising antibodies (NAbs)), cellular responses (ELISpot) and COVID-19 infection rates were assessed.ResultsFrequency of solicited self-reported AEs following vaccination was similar across groups (HC 90%, RA 86%, SLE 90%); among them, musculoskeletal AEs were more frequent in RA (HC 48% vs RA 66% (Δ95% CI CI 3 to 32.6)). Disease activity scores did not increase postvaccination. No vaccine-related serious AEs were reported. Postvaccination immunogenicity was reduced in RA and SLE (RA 90.2%, SLE 86.4%; for both, ΔCIs compared with HC excluded the null). Similarly, NAbs were reduced among patients (RA 82.6%, SLE 81.8%). In RA, age >65 (OR 0.3, 95% CI 0.1 to 0.8) and rituximab treatment (OR 0.003, 95% CI 0.001 to 0.02) were negative predictors of immunogenicity. ELISpot was positive in 16/52 tested RA and 17/26 HC (ΔCI 11.2–53.3). During the study, 11 HC, 19 RA and 3 SLE patients self-reported COVID-infection.ConclusionIn COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune Diseases, the Moderna Spikevax primary series was safe. MMF, RA age >65 and rituximab were associated with reduced vaccine-induced protection.
Excess mortality following a first and subsequent osteoporotic fracture: a Danish nationwide register-based cohort study on the mediating effects of comorbidities
Authors: Christensen Emilie Rosenfeldt , Clausen Anne , Petersen Tanja Gram , Skjødt Michael Kriegbaum , Abrahamsen Bo , Möller Sören , Rubin Katrine Hass 
Published: November 2023

ObjectivesThis study aimed to examine the risk of mortality following incident and subsequent osteoporotic fractures, the effect of different fracture type combinations, and the mediating role of postfracture morbidity in a Danish population.MethodsWe used the National Patient Registry to identify patients ≥60 years with incident major osteoporotic fracture of the hip, vertebrae, wrist or humerus between 2013 and 2018, and controls matched 1:10 on age and sex. Possible mediators were identified using International Classification of Diseases, 10th Revision codes registered in the 6 months following index fracture. HRs were estimated using Cox regression analyses with 95% CIs. The effect of possible mediators was estimated using mediation analyses.ResultsThe study included 106 303 patients and 1 062 988 controls. Mortality following index fracture was highest in the month following hip fractures (HR 10.98 (95% CI 10.23 to 11.79) in women and HR 16.40 (95% CI 15.00 to 17.93) in men). Subsequent hip fractures resulted in the highest HRs for all fracture type combinations. In women, the highest HR was observed in patients with index wrist/subsequent hip fractures (HR 2.43 (95% CI 2.12 to 2.78)). In men, the highest HR was observed in patients with index humerus/subsequent hip fractures (HR 2.69 (95% CI 2.04 to 3.54)). Pneumonia mediated the largest proportion of mortality, but dehydration, urinary tract infection and sepsis were also important factors.ConclusionsThe highest mortality risk was found in the month immediately following both index and subsequent fracture. The combination of index and subsequent fractures at different skeletal sites had a substantial impact on the risk of mortality. Postfracture morbidities were found mediate the association.
Chilling alcohol on the computer: isothermal compressibility and the formation of hydrogen-bond clusters in liquid propan-1-ol
Authors: Baptista Luis A. , Sevilla Mauricio , Wagner Manfred , Kremer Kurt , Cortes-Huerto Robinson 
Published: November 2023

Abstract
Molecular dynamics simulations have been performed to compute the isothermal compressibility $$\kappa _T$$

κ
T

of liquid propan-1-ol in the temperature range $$200 \le T\le 300$$

200
≤
T
≤
300

K. A change in behaviour, from normal (high T) to anomalous (low T), has been identified for $$\kappa _T$$

κ
T

at $$210<T<230$$

210
<
T
<
230

K. The average number of hydrogen bonds (H–bond) per molecule turns to saturation in the same temperature interval, suggesting the formation of a relatively rigid network. Indeed, simulation results show a strong tendency to form H–bond clusters with distinct boundaries, with the average largest size and width of the size distribution growing upon decreasing temperature, in agreement with previous theoretical and experimental studies. These results also emphasise a connection between the behaviour of $$\kappa _T$$

κ
T

and the formation of nanometric structures.

Graphic Abstract
Petrophysical characteristics of igneous rocks in the Outboard Browse Basin, North West Shelf of Australia: implications for predicting igneous sequences prior to exploration drilling
Authors: Tsutsui Kosuke , Holford Simon , Schofield Nick , Bunch Mark , King Rosalind , McClay Ken 
Published: November 2023

Abstract
The Browse Basin is one of Australia's major hydrocarbon provinces, where significant discoveries have been made in recent decades including the Ichthys and Prelude fields, which accounted for ∼15% of the cumulative Australian liquified natural gas (LNG) production in 2019–20. This rift basin hosts extensive Mesozoic intrusive and extrusive igneous rocks, having been identified from both well and seismic data, and which are recognized as one of the key challenges for exploration and production activities in this region. Their impact on petroleum exploration is demonstrated by the number of wells which encountered unpredicted or thicker than expected igneous rock units both within and adjacent to target sections. This study therefore aims to document the reasons of such unexpectedness, and to develop capability to predict the occurrence of igneous rock units prior to drilling in the Browse Basin and other rift settings that contain igneous rocks. Multiple case studies of uncommercial exploration wells are developed by integrating petrophysical and seismic reflection data, focusing in particular along the outboard part of the basin where igneous rocks are most prevalent. Our study highlights the importance of understanding petrophysical, spatial and chemical heterogeneities of igneous rocks in basins to explain their emplacement and distribution, and thereby predict their occurrence prior to exploration and development activities.
DEEPFAKER: A Unified Evaluation Platform for Facial Deepfake and Detection Models
Authors: Wang Li , Meng Xiangtao , Li Dan , Zhang Xuhong , Ji Shouling , Guo Shanqing 
Published: November 2023

Deepfake data contains realistically manipulated faces—its abuses pose a huge threat to the security and privacy-critical applications. Intensive research from academia and industry has produced many deepfake/detection models, leading to a constant race of attack and defense. However, due to the lack of a unified evaluation platform, many critical questions on this subject remain largely unexplored. How is the anti-detection ability of the existing deepfake models? How generalizable are existing detection models against different deepfake samples? How effective are the detection APIs provided by the cloud-based vendors? How evasive and transferable are adversarial deepfakes in the lab and real-world environment? How do various factors impact the performance of deepfake and detection models?

To bridge the gap, we design and implement
DEEPFAKER

1

a unified and comprehensive deepfake detection evaluation platform. Specifically,
DEEPFAKER
has integrated 10 state-of-the-art deepfake methods and 9 representative detection methods, while providing a user-friendly interface and modular design that allows for easy integration of new methods. Leveraging
DEEPFAKER
, we conduct a large-scale empirical study of facial deepfake/detection models and draw a set of key findings: (i) the detection methods have poor generalization on samples generated by different deepfake methods; (ii) there is no significant correlation between anti-detection ability and visual quality of deepfake samples; (iii) the current detection APIs have poor detection performance and adversarial deepfakes can achieve about 70% attack success rate on all cloud-based vendors, calling for an urgent need to deploy effective and robust detection APIs; (iv) the detection methods in the lab are more robust against transfer attacks than the detection APIs in the real-world environment; and (v) deepfake videos may not always be more difficult to detect after video compression. We envision that
DEEPFAKER
will benefit future research on facial deepfake and detection.
Religious Practices and Its Impacts on a Sustainable Urban Environment in Nigeria: The Way Forward
Authors: Ogunbode Timothy Oyebamiji , Oyekan Funke Elizabeth 
Published: November 2023

A sustainable and serene environment is a prerequisite and a driver of human productivity in space and time. The quality of a human environment, however, is under threat always partly as a result of various human cultural activities such as festivities and religious practices. This work specifically investigated various ways religious activities have impacted the urban environment in two cities in the southwestern part of Nigeria together as a case study. Data for the work were generated through the administration of 250 copies of the structured questionnaire, out of which 232 were completed and retrieved. The data were subjected to data adequacy tests (i.e., Kaiser–Meyer–Olkin (KMO) and Bartlett’s test of sphericity (BTS)). The test showed 67.6% at a significance level of

p

< 0.001 The results showed that 52.6% were of secondary school level, 52.2 were of Christian faith, and 61.6% were also of the male gender who were mostly in the age category of 46 to 65 years. The factor analysis identified 11 out of 23 variables as significant ones which explained 72.052% of the ways religious activities have negatively impacted the urban environment. Of the 11 variables, the first six alone offered 45.248%, namely, (i) contribution to climate change, (ii) night worships, (iii) noise pollution caused, (iv) use of the public address system, (v) quest for expansion, and (vi) religious uses of natural resources, especially water. In view of this, it is recommended that efforts should be made to check the extracted variables for a sustainable serene environment. However, there is a need to put in place relevant legislation/policies to control the activities of various religious bodies and mechanisms to enlighten religious practitioners on practices that will not jeopardize a serene urban environment. Further studies in other places to affirm or otherwise the findings here are suggested.