bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the impact of the Storegga tsunami on Mesolithic communities in Northumberland
Authors: Sharrocks Patrick D , Hill Jon 
Published: December 2023

ABSTRACTThe Holocene Storegga tsunami, 8120–8175 cal a bp, resulted in run‐up heights of up to 3–6 m around mainland UK and coincided with a suggested large population decline in the coastally focused Mesolithic population in Northern Britain. At Howick, Northumberland, the site of a Mesolithic settlement, a nearby sediment deposit may be of tsunamigenic origin, but this is uncertain. Here, a numerical model was used to simulate the Storegga tsunami in Northumberland. Two scenarios of relative sea‐level change, and a third incorporating high tide, were simulated with mortality estimated within the intertidal zone for the Mesolithic sites in the region. The results showed that only with the addition of high tide could the sediment deposit site have been inundated by the tsunami. At Howick, mortality estimates varied but were up to 100% within the resource‐rich intertidal zone. The tsunami inundated a large area and would have led to the loss of key resources such as hazelnuts prior to the winter months. These combined effects would have probably been replicated throughout coastal settlements in Northern Britain, possibly leading to the contemporary population decline estimated to have occurred at this time.
Colon‐Targeted Oral Delivery of Hydroxyethyl Starch–Curcumin Microcapsules Loaded with Multiple Drugs Alleviates DSS‐Induced Ulcerative Colitis in Mice
Authors: Huang Da , Zou Minglang , Xu Chenlan , Wang Yongming , Xu Zhenjin , Zhang Wancong , Tang Shijie , Weng Zuquan 
Published: December 2023

AbstractCombination therapy through colon‐targeted oral delivery of multiple drugs presents a promising approach for effectively treating ulcerative colitis (UC). However, the codelivery of drugs with diverse physicochemical properties in a single formulation remains a formidable challenge. Here, microcapsules are designed based on hydroxyethyl starch–curcumin (HES─CUR) conjugates to enable the simultaneous delivery of hydrophobic dexamethasone acetate (DA) and hydrophilic cefazolin sodium (CS), yielding multiple drug‐loaded microcapsules (CS/DA‐loaded HES─CUR microcapsules, CDHC‐MCs) tailored for colon‐targeted therapy of UC. Thorough characterization confirms the successful synthesis and exceptional biocompatibility of CDHC‐MCs. Biodistribution studies demonstrate that the microcapsules exhibit an impressive inflammatory targeting effect, accumulating preferentially in inflamed colons. In vivo experiments employing a dextran‐sulfate‐sodium‐induced UC mouse model reveal that CDHC‐MCs not only arrest UC progression but also facilitate the restoration of colon length and alleviate inflammation‐related splenomegaly. These findings highlight the potential of colon‐targeted delivery of multiple drugs within a single formulation as a promising strategy to enhance UC treatment, and the CDHC‐MCs developed in this study hold great potential in developing novel oral formulations for advanced UC therapy.
NLRP3/IL‐1β induced myeloid‐derived suppressor cells recruitment and PD‐L1 upregulation promotes oxaliplatin resistance of hepatocellular carcinoma
Authors: Liu Wenfeng , Zhang Feng , Quan Bing , Yao Fan , Chen Rongxin , Ren Zhenggang , Yin Xin 
Published: December 2023

AbstractOxaliplatin is commonly used as the first‐line chemotherapeutic agent for advanced hepatocellular carcinoma (HCC). Unfortunately, the acquired resistance, limits the effectiveness of oxaliplatin and the underlying mechanisms remain unknown. Therefore, we explored the role of NOD‐like receptor protein 3 (NLRP3)/IL‐1β in mediating oxaliplatin resistance in HCC. We observed that NLRP3/IL‐1β expression was much higher in oxaliplatin‐resistant HCC cells. To further understand its impact on drug resistance, we knocked down NLRP3 and observed that it sensitized HCC cells to the growth‐inhibitory effects of oxaliplatin and induced cell apoptosis. NLRP3/IL‐1β overexpressing tumor cells also attracted polymorphonuclear myeloid‐derived suppressor cells. Using mouse models, we demonstrated that NLRP3/IL‐1β inhibition by short hairpin RNA or MCC950 effectively overcame oxaliplatin resistance. Furthermore, NLRP3/IL‐1β inhibition resulted in reduced expression of PD‐L1. We also found that PD‐L1 antibody combined with NLRP3/IL‐1β blockade displayed significant antitumor effect in HCC. Overall, our study provides compelling evidence supporting the essential role of NLRP3/IL‐1β in conferring resistance to oxaliplatin and reshaping the immunosuppressive microenvironment in HCC. Targeting NLRP3/IL‐1β presents a potential therapeutic target for overcoming oxaliplatin resistance and reshaping microenvironment of HCC.
A novel approach to calculate weighted average cost of capital (WACC) considering debt and firm's cash flow durations
Authors: Rodríguez Rafael A. 
Published: December 2023

AbstractThis paper presents a novel approach to calculate the weighted average cost of capital (WACC) but considering additional relevant variables to be applied to a specific cash flow, free cash flow to firm (FCFF), or capital cash flow (CCF), in order to value an asset. The analytical expressions deduced for this approach, one for each case, are based not only on the ratio debt to the value of the asset and the cost of debt and equity, as in the usual expression, but also includes the debt and firm's cash flow durations. The proposed novel approach to cost of capital has key advantages in comparison to the usual expression for WACC:

It is an analytical expression that could be applied to whatever kind of debt or capital structure, not only perpetual debt or permanent capital structure.
It is a single discount rate, and for its calculation, it is not necessary to recalculate financial factors involved, which makes easier its application.
The additional financial variables involved, debt and firm's cash flow duration, allow to obtain better results for the right discount rate and for the value of an asset in the sense that the discount rate for the asset effectively will permit to reach the required level for the profitability for the investor and to cover the cost of debt.
Variation in resource competition traits among Microcystis strains is affected by their microbiomes
Authors: Baker Dylan , Godwin Casey M. , Khanam Muhtamim , Burtner Ashley M. , Dick Gregory J. , Denef Vincent J. 
Published: December 2023

AbstractFreshwater harmful algal blooms are often dominated by Microcystis, a phylogenetically cohesive group of cyanobacteria marked by extensive genetic and physiological diversity. We have previously shown that this genetic diversity and the presence of a microbiome of heterotrophic bacteria influences competitive interactions with eukaryotic phytoplankton. In this study, we sought to explain these observations by characterizing Monod equation parameters for resource usage (maximum growth rate μmax, half‐saturation value for growth Ks, and quota) as a function of N and P levels for four strains (NIES‐843, PCC 9701, PCC 7806 [WT], and PCC 7806 ΔmcyB) in presence and absence of a microbiome derived from Microcystis isolated from Lake Erie. Results indicated limited differences in maximum growth rates but more pronounced differences in half‐saturation values among Microcystis strains. The largest impact of the microbiome was reducing the minimal nitrogen concentration sustaining growth and reducing half saturation values, with variable results depending on the Microcystis strain. Microcystis strains also differed from each other in their N and P quotas and the extent to which microbiome presence affected them. Our data highlight the importance of the microbiome in altering Microcystis‐intrinsic traits, strain competitive hierarchies, and thus bloom dynamics. As quota, μmax, and Ks are commonly used in models for harmful algal blooms, our data suggest that model improvement may be possible by incorporating genotype dependencies of resource‐use parameters.
Initial validation of the Mass. General Neuropathy Exam Tool (MAGNET) for evaluation of distal small‐fiber neuropathy
Authors: Zirpoli Gary R. , Farhad Khosro , Klein Madeleine C. , Downs Sean , Klein Max M. , Oaklander Anne Louise 
Published: December 2023

AbstractIntroduction/AimsDiagnosis of small‐fiber neuropathy (SFN) is hampered by its subjective symptoms and signs. Confirmatory testing is insufficiently available and expensive, so predictive examinations have value. However, few support the 2020 SFN consensus‐case‐definition requirements or were validated for non‐diabetes neuropathies. Thus we developed the Massachusetts General Hospital Neuropathy Exam Tool (MAGNET) and measured diagnostic performance in 160 symptomatic patients evaluated for length‐dependent SFN from any cause and 37 healthy volunteers.MethodsWe compared prevalences of abnormalities (vital signs, pupil responses, lower‐limb appearance, pin, light touch, vibration and position sensitivity, great‐toe strength, muscle stretch reflexes), and validated diagnostic performance against objective SFN tests: lower‐leg skin‐biopsy epidermal neurite densities and autonomic function testing (AFT). Sensitivity/specificity, feasibility, test–retest and inter‐rater reliability, and convergence with the Utah Early Neuropathy Scale were calculated.ResultsPatients’ ages averaged 48.5 ± 14.7 years and 70.6% were female. Causes of neuropathy varied, remaining unknown in 59.5%. Among the 46 with abnormal skin biopsies, the most prevalent abnormality was reduced pin sharpness at the toes (71.7%). Inter‐rater reliability, test–retest reliability, and convergent validity excelled (range = 91.3–95.6%). Receiver operating characteristics comparing all symptomatic patients versus healthy controls indicated that a MAGNET threshold score of 14 maximized predictive accuracy for skin biopsies (0.74) and a 30 cut‐off maximized accuracy for predicting AFT (0.60). Analyzing patients with any abnormal neuropathy‐test results identified areas‐under‐the‐curves of 0.87–0.89 for predicting a diagnostic result, accuracy = 0.80–0.89, and Youden's index = 0.62. Overall, MAGNET was 80%–85% accurate for stratifying patients with abnormal versus normal neuropathy test results.DiscussionMAGNET quickly generates research‐quality metrics during clinical examinations.
Bioequivalence study followed by model‐informed dose optimization of a powder for oral suspension of 6‐mercaptopurine
Authors: Arun Bhavatharini , Joshi Mahendra , Kakkar Archana Khosa , Madki Shivkumar , Ivaturi Vijay , Chinnaswamy Girish , Banavali Shripad , Gota Vikram 
Published: December 2023

AbstractBackground6‐Mercaptopurine (6MP) is the mainstay chemotherapy for acute lymphoblastic leukemia (ALL) and is conventionally available as 50 mg tablets. A new 6MP powder for oral suspension (PFOS 10 mg/mL) was developed recently by IDRS Labs, India, intended for pediatric use. A comparative pharmacokinetics of PFOS with T. mercaptopurine was conducted to determine the dose equivalence.MethodsAn open‐label, randomized, two‐treatment, two‐period, two‐sequence, single oral dose, crossover, bioequivalence study was conducted on 51 healthy adult subjects. Post hoc, a population pharmacokinetic (PopPK) model was developed using the healthy volunteer data to perform simulations with various PFOS doses and select a bioequivalent dose. Further, to confirm the safety of PFOS in pediatrics, a simulation of 6MP and 6‐thioguanine exposures was performed by incorporating the formulation‐specific parameters derived from the healthy volunteer study into the PopPK model in childhood ALL available in literature.ResultsThe 6MP PFOS had 47% higher oral bioavailability compared to the reference product. Simulations using a two‐compartmental PopPK model with dissolution and transit compartments showed that 40 mg of PFOS was found to be equivalent to 50 mg tablets. The simulated 6‐thioguanine nucleotide concentrations in children using the dose adjusted for PFOS were between 114 and 703.6 pmol/8 × 108 RBC, which was within the range reported in pediatric ALL studies.Conclusion6MP PFOS 10 mg/mL should be administered at a 20% lower dose than the tablet to achieve comparable exposure. 6MP PFOS addresses an unmet medical need for a liquid formulation of 6MP in the Indian subcontinent.
A nursing perspective on inpatient sleep and circadian disruptions for pediatric stem cell transplant patients
Authors: Zhou Eric S. , Revette Anna , Waitt Julie , Lehmann Leslie E. , Diller Lisa R. , Emmons Karen M. , Valenzuela Ariana F. , Redline Susan 
Published: December 2023

AbstractBackgroundChildren treated with stem cell transplant (SCT) are routinely hospitalized for long periods where they are exposed to significant sleep and circadian disruptions. As nurses play a primary role in symptom management during SCT, we sought to understand their perspective on patient sleep and circadian disruptions, perceived barriers to a good sleep and circadian environment, and suggestions for improvement.ProcedureFour focus groups were conducted with pediatric SCT nurses (N = 25 participants). A semistructured focus group guide was administered, with the discussions recorded and transcribed. A multistage thematic analysis combining prefigured and emergent dimensions was conducted. Our analysis focused on drawing comparisons within and across focus groups to understand the unique work experiences that participants had related to the patient's sleep and circadian environment.ResultsThree key themes emerged. First, nurses expressed a high awareness of how disruptive the hospital environment is for patients. Second, nurses described their extensive efforts to try to minimize the impact of these disruptions. Finally, they provided clear recommendations for how to improve upon these concerns, along with barriers that they perceive could impede implementation.ConclusionsFront‐line caregivers on a pediatric SCT unit describe key contributors to sleep/circadian disturbances for patients. Within the constraints of the considerable medical needs of this patient population and the physical room/hospital environment, nurses strive to minimize these disruptions to the best of their ability. It is crucial that hospitals assess and remediate these disturbances for these children that have important implications for overall health.
Remote hands‐on training with a novel “video‐game” simulator for teaching fetoscopic laser techniques for ablation of placental anastomoses in twin‐to‐twin syndrome
Authors: Windrim Catherine , Ryan Greg , Rojas David , Montero Daniel , Higgins Mary , Windrim Rory 
Published: December 2023

Key pointsWhat's already known about this topic?

Twin to twin syndrome (TTTS) is a serious complication of monochorionic twin pregnancy
The treatment of choice is fetoscopic laser ablation of placental anastamoses
Simulation plays an important role in teaching this high‐acuity procedure

What does this study add?

We report the development of a high‐fidelity digital simulation system for teaching TTTS fetoscopic lasers
Remote teaching has been demonstrated to work well with this system
This simulator is robust, easy to store and assemble and relatively inexpensive.
A novel NONO nonsense variant in a fetus with renal abnormalities
Authors: Rodriguez‐Revenga Laia , Nadal Alfons , Borobio Virginia , Álvarez‐Mora Maria Isabel , Madrigal Irene , Pauta Montse , Borrell Antoni 
Published: December 2023

AbstractAt 16 + 6‐weeks a fetal scan performed in the second pregnancy of a 42 y.o. woman identified a right multicystic dysplastic kidney, left renal agenesis, absent urinary bladder, myocardial hypertrophy, increased nuchal fold, a single umbilical artery, and oligohydramnios. Trio exome sequencing analysis detected a novel pathogenic NONO variant. Postmortem examination after the termination of pregnancy confirmed the ultrasound findings and also revealed pulmonary hypoplasia, retrognathia and low‐set ears. The variant was a novel de novo hemizygous pathogenic loss‐of‐function variant in NONO [NM_007363.5], associated with a rare X‐linked recessive neurodevelopmental disorder, named intellectual developmental disorder, X‐linked syndromic 34 (OMIM#300967). The postnatal characteristic features of this disorder include intellectual disability, developmental delay, macrocephaly, structural abnormalities involving the corpus callosum and/or cerebellum, left ventricular noncompaction and other congenital heart defects. In the prenatal setting, the phenotype has been poorly described, with all described cases presenting with heart defects. This case highlights the need of further clinical delineation to include renal abnormalities in the prenatal phenotype spectrum.
Antifungal medication use during pregnancy and the risk of selected major birth defects in the National Birth Defects Prevention Study, 1997–2011
Authors: Papadopoulos Eleni A. , Howley Meredith M. , Fisher Sarah C. , Van Zutphen Alissa R. , Werler Martha M. , Romitti Paul A. , Browne Marilyn L. ,   for the National Birth Defects Prevention Study
Published: December 2023

AbstractPurposeRecent studies suggest increased birth defect risk associated with maternal use of specific oral antifungals. We estimated associations between first‐trimester antifungal use and selected non‐cardiac birth defects using National Birth Defects Prevention Study (NBDPS) data.MethodsParticipants with a pregnancy affected by a study‐eligible birth defect (“cases”) were ascertained from 10 birth defect surveillance programs; participants who delivered livebirths without a major birth defect (“controls”) were randomly selected from birth records or hospital discharge lists. First‐trimester antifungal use was self‐reported via maternal interview. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for birth defects with ≥5 exposed cases using logistic regression. We estimated crude ORs and exact 95% CIs for birth defects with 3–4 exposed cases. Additionally, we conducted a probabilistic bias analysis of exposure misclassification.ResultsOur analysis included 19 624 cases and 11 427 controls; 257 (1.3%) cases and 123 (1.1%) controls reported first‐trimester antifungal use. Of those who reported antifungals, 62.6% of cases and 64.2% of controls reported topical antifungals; 10.1% of cases and 4.9% of controls reported oral antifungals. We observed the strongest associations for encephalocele and Dandy‐Walker malformation and modestly elevated estimates for several other defects. Bias‐adjusted estimates were similar to the main analysis.ConclusionFirst‐trimester antifungal use was positively associated with several birth defects in our analysis, although CIs were imprecise. Further study is warranted to investigate associations between antifungal use and birth defects, including potential bias due to confounding by indication.
To retrieve values of albuminuria to define the size of CKD patients eligible to SGLT‐2Is: An explorative analysis using a primary care database
Authors: Lapi Francesco , Marconi Ettore , Piccinocchi Gaetano , Medea Gerardo , Piccinni Carlo , Maggioni Aldo Pietro , Cricelli Claudio 
Published: December 2023

AbstractPurposeTo address missingness of albuminuria values, which establish the eligibility to SGLT‐2Is for patients with CKD, using the multiple imputation (MI) method.MethodsWe selected patients aged 18 or older and diagnosed with CKD in a primary care database. Those with severe CKD and/or previously treated with SGLT‐2Is were excluded. Then, we collected all available information on albuminuria within 90 days the measure of GFR. A value of albumin‐creatinine ratio (ACR) ranging 200–5000 mg/g or otherwise was the response variable on which we ran MI. Using logistic regression, odds ratios (OR) and related 95% confidence intervals (CI) were estimated for each covariate toward the response variable for both full and imputed dataset.ResultsThe determinants showed consistent estimates between the full and imputed datasets as demonstrated by the overlaps of the CIs and the similar point estimates. As expected, there were some exceptions, such as diabetes (OR of 1.2 vs. 0.5) and use of diabetic medications (OR of 1.0 vs. 2.1) and/or statins (OR of 1.1 vs. 1.8).ConclusionsBesides being a reminder for GPs to prescribe and register albuminuria in certain patients' categories, these determinants might be translated into an operational algorithm to input ACR values in administrative data sources. Scenarios for the reimbursement criteria regulating SGLT‐2Is to treat CKD would be therefore simulated on more inferable estimates.
Austrian farmers perception of new weeds
Authors: Glaser Michael , Essl Franz , Follak Swen 
Published: December 2023

AbstractThe composition of weed floras in Central European fields has shifted creating a novel management issue: new weeds, that is, species that are currently spreading and increasing in impact. In their role as primary decision makers on the ground, farmers' perception of these new weeds plays a pivotal role in collecting information on their occurrence and control. We conducted an online survey to determine if Austrian farmers recognized 15 selected new weed taxa (12 species and 3 genera) from their farm. The 181 surveyed farmers also estimated the required management effort for these species and elicited their current management practices. Additional questions were posed to understand farmers' general perception of changes in the weed flora. We used a generalized linear mixed model to estimate differences in management effort and identify new weeds that merit monitoring and management programs. Two weed genera (Fallopia spp. and Panicum spp.) showed significantly higher than average management effort. The most commonly used management measures were manual removal, herbicide use and crop rotation. A majority of farmers reported changes in the weed flora; over two thirds reported new species and over one third reported new weeds that were difficult to control. In summary, our results suggest that respondents were aware of the challenges posed by new weeds but required more information on management and prevention strategies.