bluuebunny/crossref_metadata_2025 huggingface dataset:
ENVISION: A phase 3b/4 randomized, double‐blind, placebo‐controlled, parallel‐group study to verify the clinical benefit of aducanumab in participants with early Alzheimer’s disease
Authors: Murphy Jennifer , Aisen Paul , Barkhof Frederik , Castrillo‐Viguera Carmen , Cheng Wenting , Cohen Sharon , Hansson Oskar , He Ping , Iwatsubo Takeshi , Jaeger Judy , Montenigro Philip H. , Rubel Carrie E. , Mummery Catherine J. , O'Gorman John , Racine Annie M , Vellas Bruno , Wu Shuang , Haeberlein Samantha Budd
Published: December 2022

Background

Aducanumab is a human monoclonal antibody selective for aggregated forms of amyloid beta approved in the United States by the Food and Drug Administration (FDA) for the treatment of Alzheimer’s disease on June 7, 2021 under the accelerated approval pathway, which requires a randomized‐controlled trial with an appropriate control to verify the clinical benefit of aducanumab. On March 25, 2022 the sponsor submitted the final protocol for this trial, named ENVISION, to the FDA.

Method

ENVISION (NCT05310071) is a multicenter, randomized, double‐blind, placebo‐controlled, parallel group study in participants with mild cognitive impairment due to Alzheimer’s disease (Stage 3) and mild Alzheimer’s disease dementia (Stage 4), designed to verify the clinical efficacy and safety of aducanumab. Key enrollment criteria include MMSE score of 22‐30, age 60‐85, CDR‐G of 0.5 or 1.0, regardless of ApoE ε4 status. Participants will be randomized, to receive aducanumab or placebo in a 2:1 ratio and will be titrated to 10 mg/kg aducanumab or placebo by intravenous infusion every 4 weeks for a treatment duration of 24 months.

The primary objective is to assess the clinical benefit of monthly doses of aducanumab in slowing cognitive and functional impairment as measured by change of CDR‐SB score at 18 months as compared to placebo. Key secondary endpoints include change in ADCS‐ADL‐MCI, ADAS‐Cog13, iADRS, MMSE, and NPI‐10; other secondary endpoints include change in amyloid PET and tau PET signal. Safety endpoints include incidence of ARIA events and SAEs. Exploratory endpoints include CSF and plasma biomarkers.

Approximately 1512 participants will be enrolled across 220 centers globally. A racially/ethnically representative population will be included in the United States, with an enrollment goal of 18% Black/African American and LatinX/Hispanic patients.

Result

ENVISION will begin in Q2 2022 and read out approximately 4 years after first patient in. Primary analysis read‐out of clinical, biomarker, and safety data will be at 18 months, with additional longer‐term data on aducanumab treatment effect up to 24 months.

Conclusion

The confirmatory ENVISION trial will further explore clinical efficacy, biomarker profile, and safety of aducanumab in a racially/ethnically representative population.
Drug therapy, imaging, and other aspects of clinical management change after Alzheimer’s biomarker testing in routine practice: Findings from the IMPACT‐AD BC study
Authors: Yang David , Best John R. , Chambers Colleen , Feldman Howard H. , Pettersen Jacqueline A , Henri‐Bhargava Alexander , Lee Philip E , Nygaard Haakon B. , Funnell Clark R , Foti Dean J , Hsiung Ging‐Yuek Robin , DeMarco Mari L.
Published: December 2022

Background

While previous studies have demonstrated the effect of Alzheimer’s disease (AD) CSF testing in changing diagnosis, we lack an understanding of how this testing affects clinical management. Therefore, we assessed changes in clinical management associated with AD CSF biomarker testing when ordered as part of routine clinical management.

Method

The ‘Investigating the Impact of Alzheimer’s Disease Diagnostics in British Columbia’ (IMPACT‐AD BC) study (NCT05002699) is a longitudinal study examining the impact of AD CSF testing on clinical management, personal utility and health care economics in British Columbia, Canada. After AD CSF testing was ordered as part of routine care (where the clinical scenario met the appropriate use criteria), the patient and their physician were eligible to participate in the study. The primary outcome was the change in management (pre‐ v. post‐biomarker results) in a composite measure including 1) AD drug therapy, 2) other relevant drug therapy, 3) other diagnostic procedures, and 4) referral or counselling.

Result

Participants (n = 129) had a median age of 63 (IQR:58‐68); 49% were female. Cognitive impairment at baseline consisted of 7% with subjective cognitive impairment, 53% with mild cognitive impairment, and 40% with dementia. CSF biomarker profiles were consistent with an amyloid‐beta pathology (i.e., A+) in 72% of cases. Changes in clinical management because of testing occurred in 83% of cases including: referrals and counseling (57%), imaging (47%) and other diagnostic procedures (e.g., neuropsychological testing) (42%), and use of AD drug therapies (40%). For those with a non‐AD pre‐biomarkers diagnosis, 42% were changed to AD post‐biomarkers; for those with an AD pre‐biomarkers diagnosis, 18% were changed to non‐AD post‐biomarkers.

Conclusion

This study has revealed substantial changes in clinical management as a direct result of AD CSF biomarker testing in routine care. An understanding of the implications of biomarker testing will in turn help us: improve appropriate utilization, understand the broader impacts on persons living with dementia and on the health care system, and prepare for expanded use of this testing with the availability of disease‐modifying therapeutics.
Age‐related changes in clinically relevant biomarkers in a Beagle model of Alzheimer’s disease.
Authors: de Rivera Christina , Prenderville Jack , Araujo Joseph A
Published: December 2022

Background

Canine aging is associated with cognitive decline linked to several neuropathological changes that parallel those reported in Alzheimer’s disease including deposition of amyloid‐β, cerebral amyloid angiopathy, dystrophic neurites, reduced neurogenesis, neuronal loss, activated microglia and astrogliosis. Dogs also demonstrate domain specific cognitive decline with short‐term working memory and executive function impacted early in canine aging. One contributing factor of Alzheimer’s disease is neuroinflammation, including activation of microglia and astrocytes, which are also seen in canine brain aging. Microglia bind to soluble amyloid‐β oligomers and fibrils by various receptors including toll‐like receptors (TLR2, TLR4, TLR6 and TLR8), which is postulated to be part of the neuroinflammatory process in Alzheimer’s disease. Toll like receptor activation leads to downstream production and release of pro‐inflammatory cytokines through the NFκB signaling pathway. Activated astrocytes accumulate around senile plaques and release cytokines, and other cytotoxic molecules, when exposed to amyloid‐b, further contributing to the neuroinflammatory response. The current study sought to investigate whether concentrations of the following cytokines varied by age in canine biofluids; IL‐6, TNFα, IL‐8, IL‐10, and IL‐12.

Method

Concentrations of the aforementioned cytokines in cerebrospinal fluid and plasma from three age groups of dogs were evaluated in the current study. The young aged group included samples from dogs under 6 years of age. The middle age group included samples from dogs between 6 and 10 years of age. The aged or senior group included samples from dogs greater than 10 years of age.

Results and Conclusion

The results of the study will be presented, and we hypothesize that age‐related changes in cytokine concentrations may be used as a potential clinically relevant biomarker for evaluating the effects of putative Alzheimer’s disease therapeutics targeting neuroinflammation, particularly when used in conjunction with neuropsychological cognitive assays.
Multitarget evaluation of molecules from marine animals against Alzheimer's disease, related to gamma‐ and beta‐secretases and cathepsin B protein targets
Authors: De Blasio Paola
Published: December 2022

Background

One of the causes for Alzheimer’s disease (AD) is the secretase activity on the APP protein, producing ß‐amyloid peptides (Aß) that aggregate and accumulate in regions of the brain, causing cell death (WAKABAYASHI; STROOPER, 2008). Secretase (β and γ) inhibitors have been studied as an alternative to treatment, but they have exhibited toxicity or ineffectiveness; however, these enzymes are still considered potentially effective therapeutic targets. Besides these inhibitors, cathepsin B is considered another possible inhibitory target for its involvement in protein clearance and neuroinflammation (CHITRANSHI et al, 2021). Thus, this work aimed to analyze, by virtual screening, the inhibition of such enzymes, among molecules described from marine animals, in order to obtain a new prototype for amyloid plaques decrease.

Method

Molecules from marine animals were searched in scientific articles and prepared for docking, conducted by Swiss Dock server, to predict molecular interaction with β and γ‐secretases and cathepsin B (selected on PDB). Results were analyzed by UCSF Chimera and, by predicting the molecular interaction, the molecules were selected if they were positioned in the enzyme active site, with distance lower than 3 Å and binding energy lower than ‐5 kcal/mol.

Result

Among 50 molecules, Sebastianine A obtained a positioning exactly in the active site of the β‐secretase, presenting favorable binding energy of ‐6.74 kcal/mol and the binding distance of 2.395 Å with the amino acid Thr72. Regarding the γ‐secretase, it was observed the lowest binding energy of ‐6.86 kcal/mol, and 2.42 Å to the amino acid Lys380. Lastly, in the case of cathepsin B, it was possible to identify a distance of 3.091 Å and binding energy ‐6.45 kcal/mol to the amino acid Gln25.

Conclusion

Sebastianine A has the potential to inhibit 3 important enzymes for the AD development, in a multitarget approach, relevant for this complex disease. This result represents a promising drug candidate for this disease without cure so far.
Culture Matters in Assessment of Daily Activities: An example from Turkey in a large community sample
Authors: Ayhan Yavuz , Karahan Sevilay , Akbulut Bilal Bahadır , Topçuoğlu Esen Saka , Bilir Nazmi , Caman Ozge Karadag
Published: December 2022

Background

Demographic variables such as gender and age, within their own cultural context, might play a role in the instrumental activities of daily living (IADL). Functional evaluation of the elderly requires acknowledgement of the cultural context. In this study we aimed to determine the functional activities of cognitively normal Turkish elderly in a large community sample.

Method

1909 people over the age of 55, with no known diagnosis of neuropsychiatric/ developmental disorder, representing Turkey’s demographic structure were recruited. Modified Mini Mental State (3MS) was used as the cognitive assessment method. MMSE scores were estimated from 3MS. Participants with an MMSE score of over 25 and over 20 for educated and undereducated population respectively were determined as cognitively normal. Lawton‐Brody Instrumental Activities of Daily Living and Functional Activities Questionnaire were used to assess instrumental activities of daily living. Ordinal logistic regression analysis was used to assess the relation between the demographic variables and IADL.

Result

The data of 1503 individuals were assessed. 28.7% of the sample were over the age of 80, females comprised 52%, and 33.5% of the individuals were undereducated. Age, gender and education were asociated with IADL. Overall, individuals over 80 years of age were less independent in all instrumental acitivities. Regarding gender, male individuals were more independent on transportation, shopping, using phone, keeping track of current events and paying attention/discussing media, while females reported more independence on food preparation, housekeeping and laundry. The level of education was associated with dependence on phone use, shopping, travelling and finance, individuals with less than 5 years of education were significantly less independent on Transportation, shopping, using phone and finance management when compared with higher educated individuals.

Conclusion

The activities of daily living differed at different age, gender and education levels in Turkish population. Our results displayed differences from previous studies representing various cultures. The assessment of functional activities of daily living requires appreciation of the cultural context.
Prioritizing drug targets for Alzheimer’s Disease using a Mendelian Randomization framework integrating neuroimaging and genomics
Authors: Sreepada Lasya P ,   for Alzheimer's Disease Neuroimaging Initiative and UK Biobank
Published: December 2022

Background

Alzheimer’s Disease is a progressive neurodegenerative disorder that currently has no disease‐modifying treatment, partly due to inefficiencies in identifying and validating drug targets. Drugs with genetic support are more likely to succeed in pharmaceutical trials. Recent studies show that in vivo neuroimaging can capture changes in brain pathology and function before onset of cognitive symptoms, thereby serving as biomarkers for early diagnosis. Pharmaceutical intervention may be more effective if treatment is started earlier in the disease course. We aim to integrate imaging and genomic data to identify and prioritize gene targets for Alzheimer’s Disease treatment.

Method

We apply Mendelian Randomization (MR) to investigate the druggable genome: 3,000 genes encoding proteins that can be targeted with molecular compounds. Gene expression mimics low‐level exposure to compounds in individuals.We examine the causal effect of expression and protein quantitative trait loci (eQTL and pQTL) information, from public datasets like GTex, in relation to markers of Alzheimer’s Disease risk and progression using GWAS summary statistics. The analyses are performed and replicated using two independent, publicly available datasets from ADNI and UK Biobank, including matched cases and controls. Genomic data will be imputed with a standard reference genome and harmonized across studies.

Result

We will describe the dataset and analysis pipeline needed to run and validate an MR experiment that identifies gene targets for disease‐modifying treatment based on eQTL and pQTL data. We will report results of descriptive and inferential statistical analyses associating these genes with disease risk, onset, and progression using related outcome variables such as structural imaging biomarkers, clinical measures and cognitive test scores. We propose a small subset of these gene targets with the strongest MR evidence as optimal candidates for drug development research, including potential drug repurposing opportunities.

Conclusion

This study will identify gene targets for prioritization or repurposing in Alzheimer’s Disease drug development and clinical trials. The proposed targets are supported by genetic evidence of implication in disease risk, onset, and progression via association with neuroimaging features and cognitive scores. These results could aid pharmaceutical trials in terms of time and financial efficiency as well as increase the potential for success.
Post‐refolding stability considerations for optimization of in‐vitro refolding: L‐asparaginase as a case study
Authors: Mihooliya Kanti Nandan , Nitika Nitika , Bhambure Rahul , Rathore Anurag S.
Published: December 2022

Background

L‐Asparaginase is an essential enzyme for the food and biopharmaceutical industry. The stability, however, of L‐asparaginase is widely known to be an issue. Commercial manufacturing of any biopharmaceutical involves hold‐ups during processing, and can result in product loss if stability is an issue, as is the case with L‐asparaginase. This interplay of product intermediate stability and process design is the focus of this investigation.

Methods and Results

In this study, we propose a strategy to simultaneously increase the refolding yield and stability of refolded L‐asparaginase so as to improve overall process yield. Using one variable at a time (OVAT) experiments, urea (6 M), solubilized inclusion bodies (15 mg/ml), refolding method (step dilution), and pH (8.6) were identified as significant process parameters. A design of experiment (DOE)‐based optimization was then performed for the refolding step. The net outcome was more than a three‐fold increase in enzyme recovery (i.e., 4.90 IU/ml) compared to unoptimized conditions (i.e., 1.26 IU/ml). Further, the L‐asparaginase process intermediate was found to be stable for more than a week at room temperature and 2–8°C, while the unoptimized sample was stable at 2–8°C but did not show any activity at room temperature after 72 h.

Conclusions

The current study elucidates how process intermediate stability needs to be given due consideration during process optimization, particularly for products such as L‐asparaginase which are labile.
A Water‐Free ITIES: Ionic Liquid/Oil Interface for Base Metal Nanostructure Formation – Zn Case
Authors: Nishi Naoya , Kuroyama Yohei , Yoshida Naohiro , Yokoyama Yuko , Sakka Tetsuo
Published: December 2022

Invited for this issue's Front Cover is the group of Dr. Naoya Nishi of Kyoto University (Japan). The cover picture shows the water‐free liquid‐liquid interface between an ionic liquid and oil, where base metal nanostructures can be formed via the electron transfer reaction between metal ions on the ionic liquid side and reducing agents on the oil side of the interface. Read the full text of the Research Article at 10.1002/celc.202201000.
Large ferro–pyro–phototronic effect in 0.5Ba(Zr0.2Ti0.8)O3–0.5(Ba0.7Ca0.3)TiO3 thin films integrated on silicon for photodetection
Authors: Silva José P. B. , Gwozdz Katarzyna , Marques Luís S. , Pereira Mario , Gomes Maria J. M. , MacManus‐Driscoll Judith L. , Hoye Robert L. Z.
Published: December 2022

Coupling together the ferroelectric, pyroelectric, and photovoltaic characteristics within a single material is a novel way to improve the performance of photodetectors. In this work, we take advantage of the triple multifunctionality shown by 0.5Ba(Zr0.2Ti0.8)O3–0.5(Ba0.7Ca0.3)TiO3 (BCZT), as demonstrated in an Al/Si/SiOx/BCZT/ITO thin‐film device. The Si/SiOx acts as an n‐type layer to form a metal–ferroelectric–insulator–semiconductor heterostructure with the BCZT, and with Al and ITO as electrodes. The photo‐response of the device, with excitation from a violet laser (405 nm wavelength), is carefully investigated, and it is shown that the photodetector performance is invariant with the chopper frequency owing to the pyro‐phototronic effect, which corresponds to the coupling together of the pyroelectric and photovoltaic responses. However, the photodetector performance was significantly better than that of the devices operating based only on the pyro‐phototronic effect by a factor of 4, due to the presence of ferroelectricity in the system. Thus, after a poling voltage of −15 V, for a laser power density of 230 mW/cm2 and at a chopper frequency of 400 Hz, optimized responsivity, detectivity, and sensitivity values of 13.1 mA/W, 1.7 × 1010 Jones, and 26.9, respectively, are achieved. Furthermore, ultrafast rise and fall times of 2.4 and 1.5 µs, respectively, are obtained, which are 35,000 and 36,000 times faster rise and fall responses, respectively, than previous reports of devices with the ferro–pyro–phototronic effect. This is understood based on the much faster ferroelectric switching in ferroelectric thin films owing to the predominant 180° domains in a single direction out of plane.
Partial return calculator to compare monocrop, relay‐intercrop, and double crop production systems
Authors: Lindsey Laura E. , Richer Eric , McGlinch Gregory J. , Lindsey Alexander J.
Published: December 2022

To improve profitability, farmers are interested in relay intercrop (RI; planting a second crop prior to harvest of the first crop) and double crop (DC; planting a second crop after harvest of the first crop) systems. Economic comparisons can be challenging due to fluctuations in expenses and crop prices. To compare production systems, an Excel‐based partial return calculator was developed. The calculator includes default values for crop yields, expenses, and prices using current information. Additionally, practitioners have the option to enter and use their own values. The objectives of this management guide are to: (a) provide an overview of the calculator; (b) compare partial return of monocrop (MC), RI, and DC production systems; and (c) provide a mechanism for practitioners to use their own values to compare production systems. The partial return calculator compares six production systems, including winter wheat (Triticum aestivum L.) only, wheat + straw harvest, soybean [Glycine max (L.) Merr.] only, wheat (grown in 15‐inch row width) with soybean as a RI, wheat with soybean as a DC, and wheat + straw harvest with soybean as a DC. Partial return for each production system was calculated by subtracting costs (including economic value of P2O5 and K2O removed in harvested portions) from gross return. Using default values, wheat followed by DC soybean and straw harvest resulted in the highest partial return while wheat grown as a MC resulted in the lowest return. Although default values provide a comparison, practitioners should enter their own values to compare production systems.
Scalable Feature Engineering from Electronic Free Text Notes to Supplement Confounding Adjustment of Claims‐Based Pharmacoepidemiologic Studies
Authors: Wyss Richard , Plasek Joseph M. , Zhou Li , Bessette Lily G. , Schneeweiss Sebastian , Rassen Jeremy A. , Tsacogianis Theodore , Lin Kueiyu Joshua
Published: December 2022

Natural language processing (NLP) tools turn free‐text notes (FTNs) from electronic health records (EHRs) into data features that can supplement confounding adjustment in pharmacoepidemiologic studies. However, current applications are difficult to scale. We used unsupervised NLP to generate high‐dimensional feature spaces from FTNs to improve prediction of drug exposure and outcomes compared with claims‐based analyses. We linked Medicare claims with EHR data to generate three cohort studies comparing different classes of medications on the risk of various clinical outcomes. We used “bag‐of‐words” to generate features for the top 20,000 most prevalent terms from FTNs. We compared machine learning (ML) prediction algorithms using different sets of candidate predictors: Set1 (39 researcher‐specified variables), Set2 (Set1 + ML‐selected claims codes), and Set3 (Set1 + ML‐selected NLP‐generated features), vs. Set4 (Set1 + 2 + 3). When modeling treatment choice, we observed a consistent pattern across the examples: ML models utilizing Set4 performed best followed by Set2, Set3, then Set1. When modeling the outcome risk, there was little to no improvement beyond models based on Set1. Supplementing claims data with NLP‐generated features from free text notes improved prediction of prescribing choices but had little or no improvement on clinical risk prediction. These findings have implications for strategies to improve confounding using EHR data in pharmacoepidemiologic studies.
Association Between ABCG2, ABCB1, ABCC2 Efflux Transporter Single‐Nucleotide Variants and Irinotecan Adverse Effects in Patients With Colorectal Cancer: A Real‐Life Study
Authors: Barnett‐Griness Ofra , Rennert Gad , Lejbkowicz Flavio , Pinchev Mila , Saliba Walid , Gronich Naomi
Published: December 2022

Among patients treated with irinotecan, homozygous carriers of the UGT1A1*28 allele are at increased risk for neutropenia, but UGT1A1 genotype alone does not account for irinotecan‐induced toxicity. Our aim was to study the association between single‐nucleotide variants in genes encoding for efflux transporters of irinotecan (ABCG2, ABCB1, and ABCC2) and toxicity in real life. The source population was a cohort of patients with colorectal cancer (CRC) in Northern Israel, who had undergone genome‐wide association study. From the source population we chose the patients with CRC prescribed irinotecan, and a comparative cohort of patients with CRC treated with other anticancer systemic therapies. Using Clalit Health Services electronic medical records (including laboratory results) we ascertained hematological and gastrointestinal adverse effects and mortality, within 90 days of the first dose, as a composite outcome. There were 601 patients with CRC who received irinotecan, and 756 patients with CRC treated with other anticancer regimens. The minor allele in rs2231142 (ABCG2) was associated with lower incidence of the composite outcome (odds ratio (OR) = 0.54 (0.33, 0.91); P = 0.02) in irinotecan‐treated patients with CRC, but not in patients with CRC treated with other regimens. ABCB1 rs1045642 and ABCC2 rs3740066 were not associated with the composite outcome. In a sensitivity analysis, adjusted for UGT1A1 status and for possible demographic and clinical confounders, adjusted OR was 0.56 (0.33, 0.94) for the association between rs2231142 (ABCG2) and the composite outcome. In conclusion, we describe a novel association between the minor allele of rs2231142 in the efflux transporter gene ABCG2 and protection against severe side effects in CRC patients treating with irinotecan.
Intelligent power control of wind conversion system based on Takagi–Sugeno fuzzy model
Authors: Abderrahim Sahbi , Allouche Moez , Chaabane Mohamed
Published: December 2022

This paper comes up with a novel fuzzy control design for a wind conversion system (WCS). To do this, a boost converter is employed to adjust the rectified voltage under different wind speed levels. Initially, the boost converter model is well presented via the Takagi–Sugeno approach. Then, a T‐S fuzzy controller is designed to promptly calculate the duty cycle required for an optimal power operation. Afterward, the optimal DC current is determined and then transferred to the reference model to instantly determine the desired trajectories. These latter should be preserved so as to reach the maximum power. Following that, linear matrix inequalities (LMIs) are also used to guarantee the stability analyses and the performance. Finally, the sound performance and the validity of the suggested control schema are both proved by a numerical and some experimental results.
Analysis of per capita contributions from a spatial model provides strategies for controlling spread of invasive carp
Authors: Schoolmaster Donald R. , Coulter Alison A. , Kallis Jahn L. , Glover David C. , Dettmers John M. , Erickson Richard A.
Published: December 2022

Metapopulation models may be applied to inform natural resource management to guide actions targeted at location‐specific subpopulations. Model insights frequently help to understand which subpopulations to target and highlight the importance of connections among subpopulations. For example, managers often treat aquatic invasive species populations as discrete populations due to hydrological (e.g., lakes, pools formed by dams) or jurisdictional boundaries (e.g., river segments by country or jurisdictional units such as states or provinces). However, aquatic invasive species often have high rates of dispersion and migration among heterogenous locations, which complicates traditional metapopulation models and may not conform to management boundaries. Controlling invasive species requires consideration of spatial dynamics because local management activities (e.g., harvest, movement deterrents) may have important impacts on connected subpopulations. We expand upon previous work to create a spatial linear matrix model for an aquatic invasive species, Bighead Carp, in the Illinois River, USA, to examine the per capita contributions of specific subpopulations and impacts of different management scenarios on these subpopulations. Managers currently seek to prevent Bighead Carp from invading the Great Lakes via a connection between the Illinois Waterway and Lake Michigan by allocating management actions across a series of river pools. We applied the model to highlight how spatial variation in movement rates and recruitment can affect decisions about where management activities might occur. We found that where the model suggested management actions should occur depend crucially on the specific management goal (i.e., limiting the growth rate of the metapopulation vs. limiting the growth rate of the invasion front) and the per capita recruitment rate in downstream pools. Our findings illustrate the importance of linking metapopulation dynamics to management goals for invasive species control.
Interspecific allometric scaling in eDNA production among northwestern Atlantic bony fishes reflects physiological allometric scaling
Authors: Yates Matthew C. , Wilcox Taylor M. , Stoeckle M. Y. , Heath Daniel D.
Published: December 2022

Relating environmental DNA (eDNA) signal strength to organism abundance requires a fundamental understanding of eDNA production. A number of studies have demonstrated that eDNA production may scale allometrically—that is, larger organisms tend to exhibit lower mass‐specific eDNA production rates, likely due to allometric scaling in key processes related to eDNA production (e.g., surface area, excretion/egestion). While most previous studies have examined intraspecific allometry, physiological rates and organism surface area also scale allometrically across species. We therefore hypothesize that eDNA production will similarly exhibit interspecific allometric scaling. To evaluate this hypothesis, we reanalyzed previously published eDNA data from Stoeckle et al. (ICES Journal of Marine Science, 78(1), 293–304, 2021) which compared metabarcoding read count to organism count and biomass data obtained from trawl surveys off the New Jersey coast. Using a Bayesian model, we empirically estimated the value of the allometric scaling coefficient (“b”) for Northwestern Atlantic bony fishes to be 0.77 (credible interval = 0.64–0.92), although our model failed to converge for Chondrichthyan species. We found that integrating allometry significantly improved correlations between organism abundance and metabarcoding read count relative to traditional metrics of abundance (density and biomass) for bony fishes. Although substantial unexplained variation remains in the relationship between read count and organism abundance, our study provides evidence that eDNA production may scale allometrically across species in some contexts. Future studies investigating the relationship between eDNA signal strength and metrics of fish abundance could potentially be improved by accounting for allometry; to this end, we developed an online tool that can facilitate the integration of allometry in eDNA/abundance relationships.
General principles for assignments of communities from eDNA: Open versus closed taxonomic databases
Authors: Blackman Rosetta C. , Walser Jean‐Claude , Rüber Lukas , Brantschen Jeanine , Villalba Soraya , Brodersen Jakob , Seehausen Ole , Altermatt Florian
Published: December 2022

Metabarcoding of environmental DNA (eDNA) is a powerful tool for describing biodiversity, such as finding keystone species or detecting invasive species in environmental samples. Continuous improvements in the method and the advances in sequencing platforms over the last decade have meant this approach is now widely used in biodiversity sciences and biomonitoring. For its general use, the method hinges on a correct identification of taxa. However, past studies have shown how this crucially depends on important decisions during sampling, sample processing, and subsequent handling of sequencing data. With no clear consensus as to the best practice, particularly the latter has led to varied bioinformatic approaches and recommendations for data preparation and taxonomic identification. In this study, using a large freshwater fish eDNA sequence dataset, we compared the frequently used zero‐radius Operational Taxonomic Unit (zOTU) approach of our raw reads and assigned it taxonomically (i) in combination with publicly available reference sequences (open databases) or (ii) with an OSU (Operational Sequence Units) database approach, using a curated database of reference sequences generated from specimen barcoding (closed database). We show both approaches gave comparable results for common species. However, the commonalities between the approaches decreased with read abundance and were thus less reliable and not comparable for rare species. The success of the zOTU approach depended on the suitability, rather than the size, of a reference database. Contrastingly, the OSU approach used reliable DNA sequences and thus often enabled species‐level identifications, yet this resolution decreased with the recent phylogenetic age of the species. We show the need to include target group coverage, outgroups and full taxonomic annotation in reference databases to avoid misleading annotations that can occur when using short amplicon sizes as commonly used in eDNA metabarcoding studies. Finally, we make general suggestions to improve the construction and use of reference databases for metabarcoding studies in the future.
Slope stability evolution of a deep‐seated landslide considering a constantly deforming topography
Authors: Pfeiffer Jan , Zieher Thomas , Schneider‐Muntau Barbara
Published: December 2022

Slow‐moving deep‐seated landslides are characterised by continuous deformation, constantly changing topography and sliding‐mass geometry. Deformation rates are predominantly controlled by temporal dynamics of pore pressure. Progressing movements typically cause an over‐steepening of a landslide's foot, making these areas more susceptible to secondary slope failures and piggyback slides that, once they occur, change the geometric boundary conditions of a slope. This study presents an integrated topographic monitoring and geomechanical modelling approach, which is suitable for both model‐based replication of the landslide's hydro‐meteorological drivers and assessment of the long‐term effect of topographic changes on the stability behaviour of a large deep‐seated landslide. Parametrised at the Vögelsberg landslide (Tyrol, Austria) the integrated approach quantified considerable mass relocations between 2007 and 2020 at the landslide's foot and assessed respective effects on slope stability. Additionally, scenarios of past and future topographies were reconstructed and projected. Mass relocations of the order of 25 000 m3 were assessed between multiple airborne laser scanning acquisitions covering a period of 13 years. Based on annual uncrewed aerial vehicle laser scanning campaigns, area‐wide 3D displacements were analysed, exceeding a magnitude of 200 cm a−1 at small parts (2.500 m2) on the steeper foot of the active landslide. The main landslide body (0.28 km2) moves considerably slower with movements of 2–10 cm a−1. Besides spatio‐temporally varying hydrological drivers, topographic changes can have a severe impact on slope stability and therefore modify the spatiotemporal activity of the landslide. It is shown that, besides the hydrometeorological drivers, the varying elevation of the landslide's toe is a key parameter determining the long‐term trend of slope stability. With the presented approach the formation and evolution of the Vögelsberg landslide can be understood and explained.
Role of sustainable finance, geopolitical risk and economic growth in renewable energy investment: Empirical evidence from China
Authors: Lin Zhou , Alvarez‐Otero Susana , Belgacem Samira Ben , Fu Qinghua
Published: December 2022

The global economic recession caused by COVID‐19 has posed a severe threat to the feasibility of renewable energy projects, hampering the United Nation (UN) sustainable development goals. Sustainable financing (SF) is a crucial instrument for promoting investment in renewable energy (IRE) sources, as it is regarded as a crucial aspect in achieving long‐term sustainability. This study sheds insight on the impact of SF, geopolitical risk (GPR), economic growth (EG), and environmental regulation (ER) on IRE sources by evaluating 10 years of data from 35 Chinese energy businesses from 2012 to 2021. The data analysis is done by utilizing quantile regression and dynamic analytic techniques, demonstrating that SF, EG, and ER have a significant positive effect on IRE sources. However, GPR has a significant detrimental impact on IRE in China. This is one of the early studies to examine the crucial role of SF, GPR, EG, and ER in IRE, which is critical for environmental sustainability. In addition, it provides policymakers and environmentalists with crucial insights for developing and executing environmental strategies that can deliver long‐term benefits and meet SD goals.
Oscillations of a fluvial‐lacustrine system and its ecological response prior to the end‐Triassic: Evidence from the eastern Tethys region
Authors: Lu Ning , Wang Yongdong , Xu Yuanyuan , Li Liqin , Xie Xiaoping , Popa Mihai Emilian , Chen Hongyu , Ruhl Micha , Kürschner Wolfram Michael
Published: December 2022

The end‐Triassic mass extinction is considered one of the “Big Five” extinction events in the Phanerozoic. However, whether the terrestrial ecosystem began to deteriorate or even collapse prior to the Triassic–Jurassic (Tr‐J) transition remains controversial. Compared with the documented data from the western Tethyan region, evidence from the eastern Tethyan realm is limited. We undertake a fitting analysis of the sedimentary system, floral community successions and major geological events of the Xujiahe Formation as reflected by the Qilixia Section, Xuanhan area, northeast Sichuan Basin, China. Our results reveal an oscillating fluvial‐lacustrine depositional system during the Late Triassic, with the dominant sedimentary processes mainly controlled by the Indosinian Movement. Beside the sedimentary influence on the Xujiahe Flora, climate changes played a more important role. Fluctuating conditions to cooler and dryer climates at this time promoted diversification of gymnosperms under an overall warm and humid climate setting in the Late Triassic in the Xuanhan area. Superimposed on this oscillating long‐term climate state, ecosystem destabilization occurred over 1 million years prior to the Tr–J interval in the Xuanhan study area, possibly in response to the intensified storm and wildfire activity and the following environmental changes. Although the Xujiahe Flora always recovered from the interruption of the tectonic movement, it ultimately collapsed under extreme climatic events and ecological pressures induced by the Late Triassic Central Atlantic Magmatic Province event.
Raising the Dead? Limits of CPR and Harms of Defensive Practices
Authors: Skowronski George , Kerridge Ian , Light Edwina , McErlean Gemma , Stewart Cameron , Preisz Anne , Sheahan Linda
Published: December 2022

We describe the case of an eighty‐four‐year‐old man with disseminated lung cancer who had been receiving palliative care in the hospital and was found by nursing staff unresponsive, with clinically obvious signs of death, including rigor mortis. Because there was no documentation to the contrary, the nurses commenced cardiopulmonary resuscitation and called a code blue, resulting in resuscitative efforts that continued for around twenty minutes. In discussion with the hospital ethicist, senior nurses justified these actions, mainly citing disciplinary and medicolegal concerns. We argue that moral harms arise from CPR performed on a corpse and that legal concerns about failing to perform it are unfounded. We contend that such efforts are an unintended consequence of managerialist policies mandating do‐not‐resuscitate orders and advance care plans and of defensive practices that can value the interests of institutions and practitioners over those of patients. Health management teaching should include managerialism and its pitfalls, while clinician training should prioritize ethical reasoning and legal knowledge over defensive practice.
Assessing the knowledge, attitudes, and practices of graduating medical students towards sexual health in Lebanon
Authors: Saab Reem , Habib Paola Abi , Hamdan Mohammed , El Hayek Rawad , Daher Darine , El Hage Hassan Malika , Doumat George , El Kak Faysal
Published: December 2022

Objective

To assess the knowledge, attitudes, and practices of graduating medical students in Lebanon regarding sexual health, as well as their readiness to learn about it, and to determine the demographic and educational factors that influence our findings.

Methods

Cross‐sectional study. A self‐designed questionnaire exploring various components of sexual health was sent to 578 graduating medical students in Lebanon. Knowledge, attitude, and practice scores were computed and analyzed.

Results

The overall mean knowledge score was relatively low (2.61, range −13 to 10). A statistically significant difference was found in the mean knowledge score across religion (P = 0.028) and religiosity (P < 0.001) categories. The mean practice score also differed significantly across income groups (P = 0.010). No other significant associations were found between gender, sexuality, environment, primary source of sexual health education, or language and the mean knowledge, attitude, and practice scores.

Conclusion

Additional standardized assessment of medical students' competences in sexual health matters through diverse research models is needed. Re‐examination of existing medical curricula and inclusion of more extensive sexual health education is necessary to improve patient care.
Fetal echocardiography in a low‐income setting: relying on local Maternal‐fetal medicine experts for detection of fetal cardiac anomalies
Authors: Sium Abraham Fessehaye , Abdosh Abdulfetah Abdulkadir , Gudu Wondimu
Published: December 2022

Objective

To describe the experience of performing fetal echocardiography (FE) to detect fetal cardiac anomalies prenatally in an Ethiopian setting.

Methods

A cross‐sectional study was conducted at St Paul's Hospital Millennium Medical College (Addis Ababa, Ethiopia), from October 1, 2019 to September 30, 2020. Data for FE cases (on a risk‐factor indication basis) performed at 22–24 weeks at the hospital during the study period were collected prospectively and analyzed using SPSSS version 23. Simple descriptive statistics were used to analyze the data. Results were presented as percentages and frequencies.

Results

A total of 142 women who had FE were analyzed in this study. Fetal structural defect in other systems and maternal diabetes mellitus were the commonest indications for FE, seen in 48.2% (67/142) and 25.7% (36/142) of the participants, respectively. There were 5 cases (3.5%) of fetal cardiac anomalies among which were hypoplastic left heart syndrome, pulmonary stenosis, and cardiac tumor.

Conclusion

The prevalence of fetal cardiac anomalies in this study was found to be 3.5%. Fetal structural defects and maternal diabetes mellitus were the commonest indications for FE which is consistent with findings from previous similar studies.
Treatment for mild hypertension in pregnancy with different strategies: A systematic review and meta‐analysis
Authors: Chen Zhichao , Wang Jing , Carru Ciriaco , Chen Youren , Li Zhi
Published: December 2022

Objectives

To synthesize the evidence from randomized controlled trials (RCTs) of antihypertensive treatment for mild pregnancy hypertension.

Methods

We searched various databases from inception to June 2022, using keywords including hypertension; pregnancy; therapy; treatment; pregnancy outcomes; maternal outcomes; and perinatal outcomes. Only RCTs of antihypertensive treatment for mild hypertension in pregnancy comparing placebo/no therapy were included. We used Review Manager version 5.3 for statistical analyses.

Results

In all, eight studies were eligible, with a total of 4211 participants. Compared with control, the active treatment significantly prevented preeclampsia (OR 0.55; 95%CI, 0.39–0.78), placental abruption (OR 0.39; 95%CI, 0.17–0.91), severe hypertension (OR 0.35; 95%CI, 0.17–0.71), end–organ dysfunction (OR 0.34; 95%CI, 0.19–0.62) and preterm birth (OR 0.69; 95%CI, 0.59–0.82), with no increased risk of small for gestational age (SGA) (OR 1.25; 95%CI, 0.78–2.00), or admission to the NICU (OR 0.83; 95%CI, 0.54–1.28). Subgroup analyses demonstrated that the tight control group did not show an advantage over the less‐tight control group in improving pregnancy outcomes.

Conclusion

In pregnant women with mild pregnancy‐induced hypertension or chronic hypertension, antihypertensive treatment still provided precise benefits of improving pregnancy outcomes without increased risk in fetal outcomes.
Adapting Attachment and Biobehavioral Catch‐up for infants and young children with intellectual disabilities and developmental delays in South Africa: Reflections and recommendations from local stakeholders
Authors: Mohamed Ahmed Riaz , Sterkenburg Paula , van Rensburg Esmé , Schuengel Carlo
Published: December 2022

Attachment and Biobehavioral Catch‐up (ABC) is an intervention targeted at enhancing the socioemotional and regulatory functioning of at‐risk infants. However, to use the ABC for infants/toddlers with intellectual disabilities/developmental delays (ID/DD) and in novel cultural contexts, such as South Africa, adaptations may be required. This study aimed, therefore, to explore the opinions of clinical experts and perceptions of caregivers regarding the use of ABC for children with ID/DD in South Africa. It also sought to incorporate the experiences of families of children with ID/DD who received, and intervenors who delivered, ABC in its first implementation in South Africa. Semi‐structured interviews were conducted with 18 participants. Thematic analysis explicated 12 main themes: Intervention Strengths, Points of Concern, and Recommendations (Experts); Focus on Caregiver‐child Relationship, and Intervention Targets and Duration (Caregivers); Benefits of ABC, and Cultural Considerations (ABC Recipients); Focused and Targeted, Value of Feedback, Supportive Supervision, Working Alliance, and Challenges Experienced (ABC Intervenors). Practice and training recommendations include psychoeducation for parents and training for intervenors that is ID/DD‐specific, expanding supervision capacity, building intervenors’ cultural/linguistic sensitivity and competence, accessing referral networks, including local Community Health Workers as intervenors, and greater flexibility in how the sessions are organized.
Combining polyp diameter and polyp‐to‐bile ratio by dynamic contrast‐enhanced CT scanning can improve the diagnostic specificity of gallbladder neoplastic polyps
Authors: Li Qiwei , Xu Sunwang , Yuan Zhiqing , Zhang Yunhe , Lu Qing , Qian Lijun , Xu Jianrong , Song Yanyan , Zhao Ling , Chen Tao
Published: December 2022

Objective

This study aimed to distinguish between cholesterol and neoplastic gallbladder polyps using dynamic contrast‐enhanced CT.

Methods

The dataset retrospectively comprised 222 cases, including 106 cases of cholesterol polyps and 116 cases of neoplastic polyps (59 adenoma and 57 adenocarcinoma). The perception and Hounsfield units of the polyps and gallbladder bile were assessed by contrast‐enhanced CT, and the polyp‐to‐bile ratio (PBR) was calculated. Receiver operating characteristic (ROC) curves and area under the curve analyses were used to assess the diagnostic value of the diameter and PBR for neoplastic polyps.

Results

The diameter of cholesterol polyps was significantly smaller than that of neoplastic polyps. The proportion of perceived cholesterol polyps in the plain and arterial phases of CT were significantly lower than those of neoplastic polyps (p < .001). On the contrary, the CT values of gallbladder bile of cholesterol polyps were always significantly higher than those of neoplastic polyps (p < .001). The median PBR values of cholesterol polyps were significantly lower than those of neoplastic polyps (p ≤ .001). ROC analysis showed that diameter and a plain phase PRB had better diagnostic value for neoplastic polyps. Polyp diameter ≥ 11.95 mm and the plain phase PBR ≥1.48 were the optimal cut‐off values for diagnosis of neoplastic polyps. Combining a diameter ≥ 12 mm and a PBR in the plain phase ≥1.48 further improved neoplastic polyp diagnostic specificity and positive likelihood ratio (10.453).

Conclusions

Polyp‐to‐bile ratio in contrast‐enhanced CT scanning is a new and convenient index for identifying cholesterol and neoplastic gallbladder polyps.