bluuebunny/crossref_metadata_2025_split huggingface dataset:
PP152 Evaluation Of Reimbursement Periods In The Turkish Biosimilar Product Market (1995-2022)
Authors: Deger Sena Unluler , Vural Elif Hilal 
Published: December 2023

IntroductionBiosimilar products that would enhance the patient’s access to treatments have emerged as a product group that is becoming more widespread globally. Since Turkiye is an emerging market in the pharmaceutical area in the Middle East and North Africa region, and being a reference country in pricing processes for some countries, the number of products in the market and reimbursement decisions are important. The aim of this study is to evaluate duration of inclusion of biosimilars into reimbursement lists after registration in Turkiye.MethodsThis study used website-based information (Turkish Medicine and Medical Devices Agency Registered Products List and Detailed Pharmaceutical Price List, Social Security Institution Reimbursed Product List) to analyze the reimbursement approval duration for registered biosimilars in Turkiye after receiving registration approval. A study has been conducted on the launch period of biosimilar products to patients access with reimbursement and the evaluation period of reimbursement applications after registration approval. Even though they might not be active on the reimbursement list right now, products that have previously been approved for payment have been included.ResultsBetween 1995-2022, biosimilars of 13 active substances in total were registered by the Ministry of Health in Turkiye. Thirty-three different brands and 105 biosimilars with all pharmaceutical forms are registered. As of November 2022, 72 biosimilars were in the reimbursement list. Twenty-two of reimbursed biosimilars were deactivated or excluded from reimbursement. It is calculated that the average evaluation and approval timeline for reimbursement of biosimilars between 2009 and 2022 is 9 months. When biosimilars in the European Medicines Agency (EMA) and Turkiye are compared, 13 biosimilar active substances are licensed in Turkiye compared to 19 for the EMA. When the total number of brands is compared, it has been observed that while 33 brands are registered in Turkiye, this number is 73 for the EMA.ConclusionsThis study, in which reimbursement approval dates for registered biosimilars in Turkiye have been compared based on years and access timelines of biotechnological products, shows that biosimilars have been launched to patients access with reimbursement much faster than biotechnological products.
PP153 Efficacy And Safety of Onasemnogene Abeparvovec For The Treatment Of Patients With Spinal Muscular Atrophy Type 1: Meta-Analysis
Authors: Borges Stefani , Fernandes Brígida , Rodrigues Fernanda , Krug Bárbara , Cirilo Hérica Núbia , Schwartz Ida Vanessa , Probst Livia , Zimmermann Ivan 
Published: December 2023

IntroductionOnasemnogene abeparvovec has been approved for the treatment of spinal muscular atrophy 5q (SMA) type 1 in several countries, which calls for an independent assessment of its evidence regarding efficacy and safety.MethodsThis study results from searches conducted on databases MEDLINE, Embase, LILACS and Cochrane Library up to November 2022, supported by additional searches on registry databases and by manual searches of references listed in eligible studies. Outcomes of interest were global survival and mechanical-ventilation-free survival, improvement in motor function and treatment-related adverse events. Risk of bias was assessed via ROBINS-I and certainty of evidence via GRADE. Proportional meta-analysis models were performed when applicable.ResultsFour reports of three open-label, non-comparative clinical trials (START, STR1VE-US and STR1VE-EU) covering 67 patients were included in review. Meta-analyses of data available in a 12-month follow-up estimate a global survival of 97.6% (95% confidence interval [CI]: 92.6, 99.9; I2 = 0%, n=67), an event-free survival of 96.5% (95%CI: 90.8, 99.5; I2 = 32%, n=66) and a CHOP-INTEND score of 40 points or less proportion of 87.3% (95%CI: 69.8, 97.8; I2 = 69%, n=67). Proportions of 61.1% (95%CI: 40, 80.2; I² = 62%, n=67) of serious adverse events and of 58.4% (95%CI: 46.5, 69.8; I2 = 78%, n=67) of treatment-related adverse events are estimated. Despite the significant effect magnitude, reviewed studies were assessed as high risk of bias and as having very low certainty of evidence due to imprecision and risk of bias.ConclusionsReduced sample size and follow-up time offer uncertainties as regards the long-term benefits of the gene therapy, which strongly calls for the monitoring and assessment of results in clinical practice.
PP155 Should Breast Cancer Patients Avoid Venipuncture In The Ipsilateral Arm? A Rapid Review Of The Evidence
Authors: Pwee Keng Ho 
Published: December 2023

IntroductionThis rapid review clarified the evidence supporting avoidance of venipuncture on the ipsilateral arm in breast cancer patients who have had sentinel lymph node biopsy (SLNB) or axillary lymph node clearance (ALNC), as a preventive measure against lymphoedema.MethodsA systematic search was carried out for systematic reviews with the following elements:•Population – breast cancer patients who had SLNB or ALNC•Intervention – avoidance of venipuncture in the ipsilateral arm•Comparator –use of either arm for venipuncture•Outcomes – risk of lymphoedema in the ipsilateral armDatabases searched included PubMed (MEDLINE), Epistemonikos and the Cochrane Database of Systematic Reviews. Included reviews were critically appraised with the AMSTAR2 instrument and the primary studies were extracted and tabulated in a narrative synthesis.ResultsSix reviews were included; none of the reviews self-identified as systematic reviews in their titles/abstracts. Four reviews did report methods, including systematic search strategies and describing studies in adequate detail. However, all reviews did not meet most criteria on the AMSTAR2 checklist. The reviews concluded that the evidence base for avoiding venipuncture was inconsistent. An evidence table was consequently drawn up of the primary studies included in the reviews as a narrative synthesis of the primary evidence base.The primary evidence base comprised 12 observational studies – six prospective cohort or descriptive studies and 6 retrospective studies. These studies were inconsistent and inconclusive; studies that found an association or reported cases following ipsilateral venipuncture were subject to recall bias or other potential confounders. Guidelines or patient information recommending avoidance of ipsilateral venipuncture do so based on expert opinion rather than consistent findings from empirical studies.ConclusionsAll reviews concluded that the evidence base for avoiding venipuncture was inconsistent. Review authors consistently recognized there was no strong basis for the prevalent recommendations to avoid ipsilateral venipuncture to prevent lymphoedema. Such recommendations lead to unnecessary measures that may be detrimental to patients. Stakeholders should reconsider advice to patients in the light of existing evidence and weigh up the uncertain benefits against potential harm to patients.
PP156 Choice Of Different Implant Combinations of Total Hip Arthroplasty For Patients With Degenerative Joint Disease
Authors: Huang YuHan , Tai Ta-Wei , Wang Jung-Der , Elizabeth Ku Li Jung 
Published: December 2023

IntroductionIn Taiwan, people with hip osteoarthritis (OA) receive a total hip arthroplasty (THA). They can apply for National Health Insurance (NHI) coverage for metal-on-polyethylene (MoP) implant or USD1,313.2 co-pay for new bearing surface materials. This study aimed to report the number of first primary THAs, and calculate the costs of THA by different choices of prothesis implant.MethodsA retrospective cohort study of patients aged 50 years or older who had OA (as an indication for THA) from 1 January 2010 through to 31 December 2018 was established from Taiwan’s NHI Claims Data. The cohort was followed-up until 31 December 2019. THA Implant combinations were defined by bearing surface materials e.g., “ceramic-metal” into alumina or composites made from alumina and zirconia, including metal-on-polyethylene (MOP), ceramic-metal composite ceramic-on-polyethylene (c-COP), alumina ceramic-on-ceramic (a-COC), ceramic-metal composite ceramic-on-ceramic (c-COC). Since only MOP was covered by the NHI, patients who chose the COP or COC implant had to pay for additional costs. We used hospital costs comparison data to calculate the average out-of-pocket (OOP) costs for different implant combinations.ResultsThis study comprised 23,560 patients with first primary THA over 9 years. The number of patients of first primary THA increased from 1,802 in 2010 to 3,251 in 2018. The mean age of patients at baseline was 68 years, and the majority were women (70.6%). The share of users for each THA implant type were: MOP implant (49.2%), c-COC implant, (20.8%), a-COC implant, (6.5%), and c-COP implant, 5.9%. The average OOP costs of each implant were: USD3,578.60 for c-COC (SD=381.80), USD2,073.00 for a-COC (SD=279.80), and USD2,082.1 for c-COP (SD=334.1).ConclusionsAlthough only MOP was fully covered by NHI, only about 50% of the OA patients chose this type of implant, and 26.7 percent chose alumina and zirconia ceramic composite despite this being a much higher OOP cost. Whether choosing more expensive implants would be cost-effective for THA in Taiwan’s healthcare system requires further analysis.
Evading Capture: U.S. Army Engineers and Railroad Policy, 1827–1853
Authors: KAMINSKI ROBERT 
Published: December 2023

AbstractUntil 1838 the U.S. government lent railroads Army engineers to survey routes. Though not strictly regulators, these army engineers would consequently face powerful versions of the incentives that make regulatory capture a pervasive problem—including an intensified “revolving door,” the opportunity for institutional empire building, and a fertile ground for cognitive capture. Nevertheless, engineering officers would push to abolish federal railroad aid, succeeding by 1838. This article argues that they turned against railroad aid when the nation’s growing rail network revitalized long-standing republican hopes of replacing standing armies and fortifications with floating batteries and militias. Though this scheme was strategically quixotic, Jacksonian populism and fiscal retrenchment during the Panic of 1837 combined with the transportation revolution to make it appear a credible threat to the Corps’s institutional raison d’être—building coastal fortifications. Engineers thus turned against railroad aid to protect their core competency, highlighting underappreciated tensions between institutional and industry interests.
Eradicating the exceptional: The role of territory in structuring international legal thought
Authors: Lythgoe Gail 
Published: December 2023

AbstractThis article examines the idea of the sui generis in international law and explores how these exceptions structure international legal thought. Exceptions are useful to international law theorizing because they create easy manageable narratives which explain situations not fitting traditional paradigms, yet as a category in their own right – specifically how they are structured and how they operate – they are often undertheorized. The two examples explored in this article are sui generis actors and the concept of extraterritorial jurisdiction. I demonstrate the foundational role played by (state-)territorialized thinking in the creation of oppositional categories: state and non-state, and the non-exceptional and exceptional exercise of jurisdiction. The category of exceptions has significantly expanded from the likes of the Holy See and irregular exercise of extraterritorial jurisdiction to a broad array of actors, such as international organizations and transnational corporations, playing growing and varied roles in contemporary law-making and governance and the regular exercise of extraterritorial jurisdiction by states. Rather than continuing with this overextended category, the article argues it is instead possible, by rethinking international law’s spatial imaginary, to first, better understand the spaces of non-state actors and regularized exercise of extraterritorial jurisdiction and second, eradicate the now overstretched legal category of ‘sui generis’.
How might cancer patients experience existential guilt? A qualitative research
Authors: Arian Moslem , Khanjani Mohammad Saeed , Adams Martin , Ebadi Abbas , Younesi Seyyed Jalal , Azkhosh Manoochehr , Hosseinzadeh Samaneh 
Published: December 2023

AbstractObjectivesExistential guilt is a deep and multidimensional concept that is correlated with concepts, such as in/authenticity, existential anxiety, decisiveness, and personal and social responsibility. The aim of the present study is to investigate the experience of existential guilt among cancer patients.MethodsThe present research was conducted with a qualitative method with a content analysis design. A purposeful sampling method was used to select the participants and the sampling procedure went on until we reached data saturation. Data were obtained using semi-structured interviews with the participants.ResultsFrom a total of 18 interviews, 94 codes related to existential guilt were obtained. After the analysis, three main concepts were extracted: (1) incompleteness, (2) passivity, and (3) feelings of harm to self and others. Each of these had a number of subcategories.Significance of resultsThe participants of the present research were found to experience existential guilt in different ways. The research showed that it is necessary to find the sources of existential guilt in order that effective therapeutic attention can be given cancer patients.
Europa's Ocean Translates Interior Tidal Heating Patterns to the Ice‐Ocean Boundary
Authors: Lemasquerier D. G. , Bierson C. J. , Soderlund K. M. 
Published: December 2023

AbstractThe circulation in Europa's ocean determines the degree of thermal, mechanical and chemical coupling between the ice shell and the silicate mantle. Using global direct numerical simulations, we investigate the effect of heterogeneous tidal heating in the silicate mantle on rotating thermal convection in the ocean and its consequences on ice shell thickness. Under the assumption of no salinity or ocean‐ice shell feedbacks, we show that convection largely transposes the latitudinal variations of tidal heating from the seafloor to the ice, leading to a higher oceanic heat flux in polar regions. Longitudinal variations are efficiently transferred when boundary‐driven thermal winds develop, but are reduced in the presence of strong zonal flows and may vanish in planetary regimes. If spatially homogeneous radiogenic heating is dominant in the silicate mantle, the ocean's contribution to ice shell thickness variations is negligible compared to tidal heating within the ice. If tidal heating is instead dominant in the mantle, the situation is reversed and the ocean controls the pole‐to‐equator thickness contrast, as well as possible longitudinal variations.
Why (Still) Studying Turbulence in Fluids and Plasmas?
Authors: Alberti Tommaso , Benzi Roberto , Carbone Vincenzo 
Published: December 2023

AbstractTurbulence, a captivating and intricate phenomenon, continues to attract researchers across diverse scientific disciplines. Despite considerable efforts, turbulence remains a fascinating challenge and stands as one of the unsolved enigmas in classical physics. Researchers strive to unravel the underlying physical mechanisms and refine mathematical models to unlock a comprehensive understanding of this complex phenomenon. This paper delves into the reasons why the study of turbulence still persists for a long time, highlighting its history and fundamentals, wide‐ranging applications, significance in environmental and climate sciences, and outstanding open challenges. Through these endeavors, the quest for unraveling the mysteries of turbulence promises to yield profound scientific insights and practical applications in the years to come.
Public Health Data Applications Using the CDC Tracking Network: Augmenting Environmental Hazard Information With Lower‐Latency NASA Data
Authors: Amos H. M. , Skaff N. K. , Schollaert Uz S. , Policelli F. S. , Slayback D. , Macorps E. , Jo M. J. , Patel K. , Keller C. A. , Abue P. , Buchard V. , Werner A. K. 
Published: December 2023

AbstractExposure to environmental hazards is an important determinant of health, and the frequency and severity of exposures is expected to be impacted by climate change. Through a partnership with the U.S. National Aeronautics and Space Administration, the U.S. Centers for Disease Control and Prevention's National Environmental Public Health Tracking Network is integrating timely observations and model data of priority environmental hazards into its publicly accessible Data Explorer (https://ephtracking.cdc.gov/DataExplorer/). Newly integrated data sets over the contiguous U.S. (CONUS) include: daily 5‐day forecasts of air quality based on the Goddard Earth Observing System Composition Forecast, daily historical (1980‐present) concentrations of speciated PM2.5 based on the modern era retrospective analysis for research and applications, version 2, and Moderate Resolution Imaging Spectroradiometer (MODIS) daily near real‐time maps of flooding (MCDWD). Data integrated into the CDC Tracking Network are broadly intended to improve community health through action by informing both research and early warning activities, including (a) describing temporal and spatial trends in disease and potential environmental exposures, (b) identifying populations most affected, (c) generating hypotheses about associations between health and environmental exposures, and (d) developing, guiding, and assessing environmental public health policies and interventions aimed at reducing or eliminating health outcomes associated with environmental factors.
Interpreting clinical trial outcomes complicated by placebo response with an assessment of false-negative and true-negative clinical trials in depression using propensity-weighting
Authors: Gomeni Roberto , Hopkins Seth , Bressolle-Gomeni Françoise , Fava Maurizio 
Published: December 2023

AbstractThe objective of this study was to evaluate the performances of the propensity score weighted (PSW) methodology in a post-hoc re-analysis of a failed and a negative RCTs in depressive disorders. The conventional study designs, randomizations, and statistical approaches do not account for the baseline distribution of major non-specific prognostic and confounding factors such as the individual propensity to show a placebo effect (PE). Therefore, the conventional analysis approaches implicitly assume that the baseline PE is the same for all subjects in the trial even if this assumption is not supported by our knowledge on the impact of PE on the estimated treatment effect (TE). The consequence of this assumption is an inflation of false negative results (type II error) in presence of a high proportion of subjects with high PE and an inflation of false positive (type I error) in presence of a high proportion of subjects with low PE value. Differently from conventional approaches, the inverse of the PE probability was used as weight in the mixed-effects analysis to assess TE in the PSW analysis. The results of this analysis indicated an enhanced signal of drug response in a failed trial and confirmed the absence of drug effect in a negative trial. This approach can be considered as a reference prospective or post-hoc analysis approach that minimize the risk of inflating either type I or type II error in contrast to what happens in the analyses of RCT studies conducted with the conventional statistical methodology.
High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials
Authors: Reeves Daniel B. , Mayer Bryan T. , deCamp Allan C. , Huang Yunda , Zhang Bo , Carpp Lindsay N. , Magaret Craig A. , Juraska Michal , Gilbert Peter B. , Montefiori David C. , Bar Katharine J. , Cardozo-Ojeda E. Fabian , Schiffer Joshua T. , Rossenkhan Raabya , Edlefsen Paul , Morris Lynn , Mkhize Nonhlanhla N. , Williamson Carolyn , Mullins James I. , Seaton Kelly E. , Tomaras Georgia D. , Andrew Philip , Mgodi Nyaradzo , Ledgerwood Julie E. , Cohen Myron S. , Corey Lawrence , Naidoo Logashvari , Orrell Catherine , Goepfert Paul A. , Casapia Martin , Sobieszczyk Magdalena E. , Karuna Shelly T. , Edupuganti Srilatha 
Published: December 2023

AbstractThe Antibody Mediated Prevention (AMP) trials (NCT02716675 and NCT02568215) demonstrated that passive administration of the broadly neutralizing monoclonal antibody VRC01 could prevent some HIV-1 acquisition events. Here, we use mathematical modeling in a post hoc analysis to demonstrate that VRC01 influenced viral loads in AMP participants who acquired HIV. Instantaneous inhibitory potential (IIP), which integrates VRC01 serum concentration and VRC01 sensitivity of acquired viruses in terms of both IC50 and IC80, follows a dose-response relationship with first positive viral load (p = 0.03), which is particularly strong above a threshold of IIP = 1.6 (r = -0.6, p = 2e-4). Mathematical modeling reveals that VRC01 activity predicted from in vitro IC80s and serum VRC01 concentrations overestimates in vivo neutralization by 600-fold (95% CI: 300–1200). The trained model projects that even if future therapeutic HIV trials of combination monoclonal antibodies do not always prevent acquisition, reductions in viremia and reservoir size could be expected.
Induced formation of primordial germ cells from zebrafish blastomeres by germplasm factors
Authors: Wang Xiaosi , Zhu Junwen , Wang Houpeng , Deng Wenqi , Jiao Shengbo , Wang Yaqing , He Mudan , Zhang Fenghua , Liu Tao , Hao Yongkang , Ye Ding , Sun Yonghua 
Published: December 2023

AbstractThe combination of genome editing and primordial germ cell (PGC) transplantation has enormous significance in the study of developmental biology and genetic breeding, despite its low efficiency due to limited number of donor PGCs. Here, we employ a combination of germplasm factors to convert blastoderm cells into induced PGCs (iPGCs) in zebrafish and obtain functional gametes either through iPGC transplantation or via the single blastomere overexpression of germplasm factors. Zebrafish-derived germplasm factors convert blastula cells of Gobiocypris rarus into iPGCs, and Gobiocypris rarus spermatozoa can be produced by iPGC-transplanted zebrafish. Moreover, the combination of genome knock-in and iPGC transplantation perfectly resolves the contradiction between high knock-in efficiency and early lethality during embryonic stages and greatly improves the efficiency of genome knock-in. Together, we present an efficient method for generating PGCs in a teleost, a technique that will have a strong impact in basic research and aquaculture.