bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and Characterization of Low-Cost Zirconium Nanocomposites as Novel Adsorbents for Arsenazo III Pollutant
Authors: Eliwa Ahmed A. , Abdel-Razik Ahmed M. , Hagag Mohamed S. , Ismail Ahmed M. , Mubark Amal E. 
Published: September 2024

Abstract Removing contaminated Arsenazo III dye from contaminated effluent is a challenge and of great interest due to its hazard and environmental impact. Therefore, the biggest challenge was producing highly efficient, easy to recycle, and economically inexpensive adsorbent materials for the contaminated dye. Three chemically stable zirconium nanocomposites with unique properties were synthesized by gel-precipitation technology. The composition, chemical, and physical properties of zirconium molybdate, tungstate, and silicate nanocomposites have been extensively proven using many different and appropriate devices such as XRD, SEM–EDX, TEM, FT-IR, BET, DLS, TGA-DTA, and zeta potential. By utilizing the most effective adsorption techniques, Azo-dye was successfully bound to ZrMo-NPs, ZrW-NPs, and ZrSi-NPs composites. The uptake capacities for these composites were measured at 0.29, 0.79, and 1.61 mmol.g−1, respectively. The sorption parameters were optimized as follows: a feed solution pH of 3 for ZrMo-NPs, a pH of 2.3 for ZrW-NPs, and a pH of 2.3 for ZrSi-NPs. The stirring time was set at 30 min, the metal ion concentration was 1.64 mmol L−1, and the sorbent dose was 7.5 mg. The adsorption results agreed well with the Langmuir isotherm and the pseudo-second-order reaction models and demonstrated the endothermic nature and kinetic improvement by increasing temperatures. The three nanocomposites effectively eliminated tainted dye from lab wastewater, offering promise for their potential applications in the future.
Graphical Abstract
Large-scale genome-wide interaction analyses on multiple cardiometabolic risk factors to identify age-specific genetic risk factors
Authors: Ao Linjun , van Heemst Diana , Luo Jiao , Teder-Laving Maris , Mägi Reedik , Frikke-Schmidt Ruth , Willems van Dijk Ko , Noordam Raymond 
Published: September 2024

AbstractThe genetic landscape of cardiometabolic risk factors has been explored extensively. However, insight in the effects of genetic variation on these risk factors over the life course is sparse. Here, we performed genome-wide interaction studies (GWIS) on different cardiometabolic risk factors to identify age-specific genetic risks. This study included 270,276 unrelated European-ancestry participants from the UK Biobank (54.2% women, a median age of 58 [interquartile range (IQR): 50, 63] years). GWIS models with interaction terms between genetic variants and age were performed on apolipoprotein B (ApoB), low-density lipoprotein-cholesterol (LDL-C), log-transformed triglycerides (TG), body mass index (BMI) and systolic blood pressure (SBP). Replication was subsequently performed in the Copenhagen General Population Study (CGPS) and the Estonian Biobank (EstBB). Multiple lead variants were identified to have genome-wide significant interactions with age (Pinteraction < 1e − 08). In detail, rs429358 (tagging APOE4) was identified for ApoB (Pinteraction = 9.0e − 14) and TG (Pinteraction = 5.4e − 16). Three additional lead variants were identified for ApoB: rs11591147 (R46L in PCSK9, Pinteraction = 3.9e − 09), rs34601365 (near APOB, Pinteraction = 8.4e − 09) and rs17248720 (near LDLR, Pinteraction = 2.0e − 09). Effect sizes of the identified lead variants were generally closer to the null with increasing age. No variant-age interactions were identified for LDL-C, SBP and BMI. The significant interactions of rs429358 with age on ApoB and TG were replicated in both CGPS and EstBB. The majority of genetic effects on cardiometabolic risk factors remain relatively constant over age, with the noted exceptions of specific genetic effects on ApoB and TG.
Residual Risks of Thrombotic Complications in Anticoagulated Patients with Atrial Fibrillation: A Cluster Analysis Approach from the GLORIA-AF Registry
Authors: Ishiguchi Hironori , Abdul-Rahim Azmil H. , Huang Bi , Lam Steven Ho Man , Liu Yang , Olshansky Brian , Chao Tze-Fan , Huisman Menno V. , Lip Gregory Y. H. ,   on behalf of the GLORIA-AF Investigators
Published: September 2024

Abstract
Background
Assessment of residual thromboembolic risk in patients with atrial fibrillation (AF) prescribed oral anticoagulants (OACs) remains unexplored. We performed hierarchical cluster analysis to identify phenotypic profiles of these patients and their risks of residual thromboembolic events.

Methods
We utilised data from non-valvular AF patients on OACs, as documented in phases II and III of the GLORIA-AF (Global Registry on Long-Term Oral Anti-thrombotic Treatment in Patients With Atrial Fibrillation) registry. We performed a hierarchical cluster analysis to identify distinct phenotypic profiles. We compared the incidence and risks of thromboembolic events (composite of ischaemic stroke, transient ischaemic attack, or systemic embolism) and related outcomes (major bleeding and all-cause death) across the profiles. We determined the optimal number of profiles through visual inspection of the generated dendrograms.

Results
We included 22,410 patients (mean age 70 ± 8 years; 56% male), from which five phenotypes were identified: profile 1 (“uncontrolled hypertension”), profile 2 (“young with a history of coronary artery disease”), profile 3 (“young and obese”), profile 4 (“frailty”), and profile 5 (“non-paroxysmal AF with tachycardia”). Profile 4 was associated with the highest rates of thromboembolic events (1.66/100 person-years [95% confidence interval, 1.46–1.89]), major bleeding (1.92/100 person-years [1.70–2.16]), and death (6.02/100 person-years [5.62–6.43]). Profile 3 was associated with the lowest risk across all measured outcomes (thromboembolic events, 0.64 events/100 person-years [0.48–0.82]; major bleeding, 0.83 events/100 person-years [0.65–1.04]; and death, 1.44 events/100 person-years [1.21–1.71]). Profile 1 had a moderate thromboembolic event rate (1.04/100 person-years [0.91–1.08]), while profiles 2 and 5 showed lower rates.

Conclusions
The phenotypic profiles of patients with AF prescribed OACs identified using hierarchical cluster analysis are associated with distinct residual thromboembolic risks and related outcomes. This approach has the potential to enhance patient risk-stratification and holistic approaches to management.

Graphical Abstract
AF, atrial fibrillation; CAD, coronary artery disease; F/U, follow-up; HTN, hypertension; IS, ischaemic stroke; NVAF, nonvalvular atrial fibrillation; OACs, oral anticoagulants; PAF, paroxysmal atrial fibrillation; SE, systemic embolism; TE, thromboembolism; TIA, transient ischaemic attack
A Screen of Plant-Based Natural Products Revealed That Quercetin Prevents Pyroglutamylated Amyloid-β (Aβ3(pE)-42) Uptake in Astrocytes As Well As Resulting Astrogliosis and Synaptic Dysfunction
Authors: Arndt Helene , Bachurski Mark , Yuanxiang PingAn , Franke Katrin , Wessjohann Ludger A. , Kreutz Michael R. , Grochowska Katarzyna M. 
Published: September 2024

Abstract
Two connected histopathological hallmarks of Alzheimer’s disease (AD) are chronic neuroinflammation and synaptic dysfunction. The accumulation of the most prevalent posttranslationally modified form of Aβ1–42, pyroglutamylated amyloid-β (Aβ3(pE)-42) in astrocytes is directly linked to glial activation and the release of proinflammatory cytokines that in turn contribute to early synaptic dysfunction in AD. At present, the mechanisms of Aβ3(pE)-42 uptake to astrocytes are unknown and pharmacological interventions that interfere with this process are not available. Here we developed a simple screening assay to identify substances from a plant extract library that prevent astroglial Aβ3(pE)-42 uptake. We first show that this approach yields valid and reproducible results. Second, we show endocytosis of Aβ3(pE)-42 oligomers by astrocytes and that quercetin, a plant flavonol, is effective to specifically block astrocytic buildup of oligomeric Aβ3(pE)-42. Importantly, quercetin does not induce a general impairment of endocytosis. However, it efficiently protects against early synaptic dysfunction following exogenous Aβ3(pE)-42 application.
Evidential Incognizance
Authors: Rippon Simon 
Published: September 2024

AbstractIn this article, I explore an epistemic vice I call “evidential incognizance.” It is a vice of failing generally to recognize evidence, or recognize the full force of evidence, in a domain of knowledge. It frequently manifests as a kind of unbridled skepticism or hopelessness about knowing in the domain, including (but not limited to) skepticism about expert testimony. It is epistemically vicious primarily because it leads people to overlook valuable epistemic opportunities, and thus tends to obstruct knowledge and justified belief. I believe it is of interest particularly because it tends to arise as a reaction to a certain kind of information environment and is often induced intentionally by populist candidates and authoritarian regimes. I discuss the nature of evidential incognizance, its relation to and differences from other epistemic shortcomings, its political significance, why it may have been previously overlooked in the literature, and the potential for overcoming it.
Generative AI and large language models in nuclear medicine: current status and future prospects
Authors: Hirata Kenji , Matsui Yusuke , Yamada Akira , Fujioka Tomoyuki , Yanagawa Masahiro , Nakaura Takeshi , Ito Rintaro , Ueda Daiju , Fujita Shohei , Tatsugami Fuminari , Fushimi Yasutaka , Tsuboyama Takahiro , Kamagata Koji , Nozaki Taiki , Fujima Noriyuki , Kawamura Mariko , Naganawa Shinji 
Published: September 2024

Abstract
This review explores the potential applications of Large Language Models (LLMs) in nuclear medicine, especially nuclear medicine examinations such as PET and SPECT, reviewing recent advancements in both fields. Despite the rapid adoption of LLMs in various medical specialties, their integration into nuclear medicine has not yet been sufficiently explored. We first discuss the latest developments in nuclear medicine, including new radiopharmaceuticals, imaging techniques, and clinical applications. We then analyze how LLMs are being utilized in radiology, particularly in report generation, image interpretation, and medical education. We highlight the potential of LLMs to enhance nuclear medicine practices, such as improving report structuring, assisting in diagnosis, and facilitating research. However, challenges remain, including the need for improved reliability, explainability, and bias reduction in LLMs. The review also addresses the ethical considerations and potential limitations of AI in healthcare. In conclusion, LLMs have significant potential to transform existing frameworks in nuclear medicine, making it a critical area for future research and development.
Dredged Canals, Wetland Loss, and Legacy
Authors: Turner R. Eugene , Ohimain Elijah I. 
Published: September 2024

AbstractThe direct effects of converting coastal wetlands to open water by dredging them can be magnified by indirect effects. For example, dredged canals allow for recovery of mineral fluids 1000 s of m belowground which may induce geological subsidence or faulting; the dredged material deposited at the surface creates levees that redirect overland water flows. These indirect factors may stress wetland plants enough so that additional wetland habitat is converted to open water as a result of longer intervals of wetland soil waterlogging and drying, sulfide toxicity, less organic matter and sediment accumulation, and greater erosion. We quantified the indirect effects by demonstrating a robust dose–response relationship between coastal land loss and canal density in the Mississippi and Niger river deltas over 5 decades. Importantly, the ratio of land loss to canal area increases with time—a legacy effect. Surface impediments to water movements rather than belowground subsidence are the dominant causal factor. We also found that flood protection levees on the main river channel did not significantly magnify the effect of dredging on wetland loss. The cumulative effect of these direct and indirect consequences in coastal Louisiana is enormous and continuing, equaling many tens of billions dollars annually. Understanding these effects supports the rejection of a hypothesis that regional river channel flood protection levees or fluid withdrawal is of greater importance than the local changes in wetland hydrology. Wetland restoration/mitigation of dredging impacts on these two coasts can be implemented at a relatively low cost and quickly if this paradigm of the causes of coastal wetland losses is adopted.
Hemodynamic Analysis in Aortic Dilatation after Arterial Switch Operation for Patients with Transposition of Great Arteries Using Computational Fluid Dynamics
Authors: Park Woo Young , Lee Sang Yun , Seo Jongmin 
Published: September 2024

AbstractAfter an arterial switch operation for complete transposition of the great arteries, neo-aortic root dilatation occurs, with unclear hemodynamic effects. This study analyzes three groups (severe dilation, mild dilation, and normal) using computational fluid dynamics (CFD) on cardiac CT scans. Aortic arch angles in severe (median 72.3, range: 68.5–77.2) and mild dilation (76.6, 71.1–85.2) groups are significantly smaller than the normal group (97.3, 87.4–99.0). In the normal and mild dilatation groups, Wall Shear Stress (WSS) exhibits a consistent pattern: it is lowest at the aortic root, gradually increases until just before the bend in the aortic arch, peaks, and then subsequently decreases. However, severe dilation shows disrupted WSS patterns, notably lower in the distal ascending aorta, attributed to local recirculation. This unique WSS pattern observed in severely dilated patients, especially in the transverse aorta. CFD plays an essential role in comprehensively studying the pathophysiology underlying aortic dilation in this population.
Graphical Abstract
Breast cancer drugs: FDA approval, development time, efficacy, clinical benefits, innovation, trials, endpoints, quality of life, value, and price
Authors: Michaeli Julia Caroline , Michaeli Thomas , Trapani Dario , Albers Sebastian , Dannehl Dominik , Würstlein Rachel , Michaeli Daniel Tobias 
Published: September 2024

Abstract
Objective
This study analyzes the development, benefits, trial evidence, and price of new breast cancer drugs with US Food and Drug Administration (FDA) approval.

Methods
We identified 26 drugs with 42 FDA-approved indications for early and metastatic breast cancer (2000–2023). Data were collected from FDA labels, clinicaltrials.gov, and Medicare and Medicaid. Overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) and tumor response’s relative risk (RR) alongside objective response rate (ORR) were meta-analyzed.

Results
The median development time for breast cancer drugs was 7.8 years (95% CI 6.2–10.8). 26% of treatments were considered innovative (“first-in-indication”) with 88% acting via a targeted mechanism. 64% were small molecules, 19% antibodies, and 18% antibody-drug conjugates. 38% were approved for HR + and 31% for HER2 + breast cancer. 6 indications were for early and 36 for metastatic breast cancer. Indications utilized FDA’s special programs: orphan (2%), fast track (24%), accelerated approval (19%), priority review (74%), breakthrough therapy (44%). Approval was predominantly supported by phase 3 trials (88%) of randomized controlled design (66%), enrolling a median of 585 patients (IQR 417–752) at 181 centers (IQR 142–223) across 19 countries (IQR 17–20). New drugs’ HR were 0.78 for OS (95% CI 0.74–0.82) and 0.59 for PFS (95% CI 0.54–0.64) with a RR for tumor response of 1.61 (95% CI 1.46–1.76). Median improvements of OS were 2.8 months (IQR 1.8–5.8) and PFS were 4.4 months (IQR 2.2–7.1). In single-arm trials, the average ORR was 31% (95% CI 10–53). In meta-regressions, the correlation between OS/PFS was 0.34 (p = 0.031) and OS/response was 0.01 (p = 0.435). 60% of treatments had a ‘high-value’ ESMO-MCBS score with 14% demonstrating improvements in quality of life. The median price was $16,013 per month (95% CI 13,097–17,617). There was no association between prices and patient benefit. The median value per life year gained was $62,419 (IQR 25,840–86,062).

Conclusions
Over the past two decades, the development of innovative and effective drugs transformed the treatment landscape for breast cancer patients. Yet, investigators and regulators must safeguard that highly-priced new drugs demonstrate improvements in patient-centered clinical endpoints: overall survival and quality of life.
Causal relationship between Lipdome and Chronic Obstructive Pulmonary Disease and Asthma: Mendelian randomization
Authors: Wu Qiong , Fu Jingmin , Zhang Cheng , Liu Zhuolin , Shi Jianing , Feng Zhiying , Wang Kangyu , Li Ling 
Published: September 2024

AbstractGenetic risk significantly influence susceptibility and heterogeneity of chronic obstructive pulmonary disease (COPD) and asthma, and increasing evidence suggests their close association with lipdome. However, their causal relationship remains unclear. In this study, we conducted a two-sample MR (Mendelian randomization) analysis using publicly available large-scale genome-wide association studies (GWAS) data to evaluate the causal impact of lipdome on COPD and asthma. The inverse variance weighted (IVW) method served as the primary analysis method, and multiple sensitivity and heterogeneity tests were performed to assess the reliability of the results. Finally, a Meta-analysis was conducted on lipdome with significant causal relationships to validate the robustness of the results. Our findings suggest that Sterol ester (27:1/18:2), Phosphatidylcholine (15:0_18:2), (16:0_18:2), (16:0_20:2), (17:0_18:2), (18:1_18:1), (18:1_18:2), (18:1_20:2), Triacylglycerol (54:3), and (56:4) levels are protective factors for COPD, while levels of Phosphatidylcholine (16:0_22:5), (18:0_20:4), and (O-16:0_20:4) are risk factors for COPD. Meta-analysis of lipids causally related to COPD also indicates significant results. Phosphatidylcholine (16:0_20:4), (16:0_22:5), and (18:0_20:4) levels are risk factors for asthma, while Phosphatidylcholine (18:1_18:2), (18:1_20:2), and Sphingomyelin (d38:1) levels are protective factors for asthma. However, the lack of statistical significance in the Meta-analysis may be due to heterogeneity in research methods and data statistics. This study indicates that 4 lipdome species have significant correlations with COPD and asthma. Phosphatidylcholine (18:1_18:2) and (18:1_20:2) are protective factors, while Phosphatidylcholine (16:0_22:5) and (18:0_20:4) are risk factors. Additionally, due to differences in molecular subtypes, phosphatidylcholine, sterol ester, and triacylglycerol exhibit differential effects on the diseases.
Oral delivery of stabilized lipid nanoparticles for nucleic acid therapeutics
Authors: Suri Kanika , Pfeifer Liam , Cvet Donna , Li Angela , McCoy Michael , Singh Amit , Amiji Mansoor M. 
Published: September 2024

AbstractGastrointestinal disorders originate in the gastrointestinal tract (GIT), and the therapies can benefit from direct access to the GIT achievable through the oral route. RNA molecules show great promise therapeutically but are highly susceptible to degradation and often require a carrier for cytoplasmic access. Lipid nanoparticles (LNPs) are clinically proven drug-delivery agents, primarily administered parenterally. An ideal Orally Delivered (OrD) LNP formulation should overcome the diverse GI environment, successfully delivering the drug to the site of action. A versatile OrD LNP formulation has been developed to encapsulate and deliver siRNA and mRNA in this paper. The formulations were prepared by the systematic addition of cationic lipid to the base LNP formulation, keeping the total of cationic lipid and ionizable lipid to 50 mol%. Biorelevant media stability depicted increased resistance to bile salt mediated destabilization upon the addition of the cationic lipid, however the in vitro efficacy data underscored the importance of the ionizable lipid. Based on this, OrD LNP was selected comprising of 20% cationic lipid and 30% ionizable lipid. Further investigation revealed the enhanced efficacy of OrD LNP in vitro after incubation in different dilutions of fasted gastric, fasted intestinal media, and mucin. Confocal imaging and flow cytometry confirmed uptake while in vivo studies demonstrated efficacy with siRNA and mRNA as payloads. Taken together, this research introduces OrD LNP to deliver nucleic acid locally to the GIT.Graphical Abstract
Pediatric Clostridioides difficile Infection: Essential Concepts, Management Nuances, and Updates
Authors: Winkie Colin , Gisser Jonathan 
Published: September 2024

AbstractPurpose of reviewAlthoughClostridioides difficile(C. difficile) infection (CDI) is generally considered a healthcare-associated infection, community transmission is more common in children. As such, CDI may be encountered by pediatric generalists and specialists in a variety of clinical settings. Differentiating between colonization and true infection poses a challenge due to overlap of symptoms with other conditions, and variable performance characteristics of available diagnostic tests. Over-diagnosing pediatric CDI can lead to over-treatment and inadvertently to recurrent CDI with implications for community health. This review, therefore, aims to familiarize the practitioner with the nuances of diagnosis and treatment and summarize the most recent advances in the management of pediatric CDI.Recent findingsMultistep algorithms that utilize PCR- and immunoassay-based tests are increasingly being employed to rapidly detect toxigenic strains ofC. difficileand more reliably differentiate between infection and colonization. Once a true infection is confirmed, a range of treatment options is available including conventional antibiotics like vancomycin, newer antimicrobials such as fidaxomicin, and microbiota-based therapies like fecal microbiota transplantation and novel well-defined bacterial preparations designed to correct dysbiosis. There are also now limited pediatric data regarding Bezlotuxumab, a monoclonal antibody which neutralizesC. difficiletoxin B, preventing recurrence of infection.SummaryRecognizing true CDI in children and selecting the appropriate therapy can be challenging. Understanding the role of microbiota, along with the pathophysiology and risk factors associated with CDI, is crucial for accurate diagnosis, effective treatment, and the prevention of recurrences.
Day-of-the-week effect: a meta-analysis
Authors: Grebe Leonard , Schiereck Dirk 
Published: September 2024

AbstractThis study conducts a meta-analysis on the day-of-the-week effect to shed more light on the replication crisis of this stock market anomaly. The findings confirm that Mondays and Tuesdays provide, on average, lower daily returns. In addition, Wednesdays and Fridays indicate higher returns, with an unexpectedly strong middle-of-the-week effect on Wednesdays. The study highlights the influence of study design on these findings and notes a more substantial effect in the 1980s and 1990s. While differences in empirical methods do not impact the anomaly, index choices affect findings on day-dependent returns. The real estate sector especially stands out with a stronger day-of-the-week effect. However, geographic differences are mostly insignificant except for Oceania. Cultural differences demonstrate a weak but significant effect on abnormal daily returns. From a meta-perspective, outliers remain an essential driver for this stock market anomaly, indicating that study design is not the only factor driving the replication crisis.