bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relative Bioavailability Studies With Mitapivat: Formulation and Food Effect Assessments in Healthy Subjects
Authors: Iyer Varsha , Sullivan Karen , Yan Yan , Hawkins Peter 
Published: October 2024

AbstractPyruvate kinase (PK) deficiency is a rare, hereditary, hemolytic anemia caused by mutations in the PKLR gene encoding the PK enzyme. Mitapivat (previously designated AG‐348) is a first‐in‐class, oral, allosteric activator of PK. We report results from 5 Phase 1 trials in healthy adults to characterize and compare mitapivat pharmacokinetics across different formulations and analyze food effects on mitapivat bioavailability (Studies 1‐5). Pharmacokinetic assessments were peak exposure, total exposure, time to maximum plasma concentration of mitapivat, and relative bioavailability (where appropriate). Plasma total exposure of mitapivat was similar in the fasted and fed (high‐fat meal or different soft foods) states after capsule, tablet, and pediatric granule formulations. Although mitapivat administration with food reduced the rate of mitapivat absorption (delay in time to maximum plasma concentration; reduction in maximum concentration) versus dosing under fasted conditions, this was not considered clinically relevant, given the lack of effect on total mitapivat exposure. Consequently, the administration instructions for mitapivat relating to food state that “patients may take mitapivat tablets with or without food.” These findings will continue to inform clinical studies and development of mitapivat in adult and pediatric patients with hemolytic anemias and may help inform healthcare professionals on mitapivat dosing/administration recommendations in clinical practice.
Synthesis of N3‐Methyluridine‐ and 2′‐O‐Alkyl/2′‐Fluoro‐N3‐Methyluridine‐Modified Phosphoramidites and Their Incorporation into DNA and RNA Oligonucleotides
Authors: Sahoo Avijit , Gore Kiran R. 
Published: October 2024

AbstractIn this article, we describe the synthesis of N3‐methyluridine (m3U) and 2′‐O‐alkyl/2′‐fluoro‐N3‐methyluridine (2′‐O‐alkyl/2′‐F‐m3U) phosphoramidites as well as their incorporation into a 14‐mer DNA and RNA oligonucleotide sequence. Synthesis of the 2′‐O‐alkyl‐m3U phosphoramidite starts with commercially available uridine to achieve a tritylated m3U intermediate, followed by 2′‐O‐alkylation and finally phosphitylation. Synthesis of the 2′‐F‐m3U phosphoramidite is obtained from a commercially available 2′‐F‐uridine nucleoside. These phosphoramidite monomers are compatible with DNA and RNA oligonucleotide synthesis using conventional phosphoramidite chemistry. This strategy offers efficient synthetic access to various modifications at the 2′‐position of m3U that can be employed in numerous nucleic acid–based therapeutic applications, including antisense technologies, small interfering RNAs, CRISPR‐Cas9, and aptamers. The data presented in this article are based on our previously published reports. © 2024 Wiley Periodicals LLC.Basic Protocol 1: Synthesis of 2′‐O‐alkyl‐N3‐methyluridine analogs and their corresponding phosphoramiditesAlternate Protocol 1: Synthesis of 2′‐O‐TBDMS‐N3‐methyluridine and its phosphoramiditeAlternate Protocol 2: Synthesis of 2′‐fluoro‐N3‐methyluridine and its phosphoramiditeBasic Protocol 2: Solid‐phase synthesis of N3‐methyluridine‐modified DNA and RNA oligonucleotides
Contrasting effects of shooting disturbance on the movement and behavior of sympatric wildfowl species
Authors: Ozsanlav‐Harris Luke , McIntosh Aimée L. S. , Griffin Larry R. , Hilton Geoff M. , Cao Lei , Shaw Jessica M. , Bearhop Stuart 
Published: October 2024

AbstractHuman−wildlife conflict is a global conservation issue, necessitating effective mitigation strategies. Hunting is a common management approach to reduce conflict, but the indirect consequences are often overlooked. Chronic hunting‐related disturbance can reduce fitness and redistribute species. In recent decades, goose−agricultural conflict has intensified due to increasing abundance and shifts towards agricultural foraging. On Islay, Scotland, escalating conflict culminated in shooting Greenland barnacle geese Branta leucopsis to reduce damage to agricultural grassland. In this study, we contrast the impact of shooting disturbance on the movement, behavior, energy expenditure and habitat selection of the target species (Greenland barnacle goose) and a vulnerable nontarget species (Greenland white‐fronted goose, Anser albifrons flavirostris) using biologging devices (target species: n = 33; nontarget species: n = 94). Both species were displaced by shooting, and greater distances were subsequently traveled by the target species (1.71 km when directly targeted). When disturbed at any distance, total daily movement increased significantly by 1.18 km for the target species but not for the nontarget species. The target species exhibited no accompanying change in diurnal energy expenditure (measured via accelerometery) but foraged in improved grasslands further from roads after shooting disturbance, where disturbance from all sources was likely lower. The significant increases in movement and changes in foraging site selection of the target species could reduce fitness but given the infrequency of shooting disturbances (0.09 per day) there is likely capacity for compensatory feeding to recoup energetic losses. The nontarget species expectedly showed no significant change in energy expenditure, behavior or habitat selection following shooting disturbance, suggesting mitigation strategies have been effective at minimizing fitness impacts. Refuge areas with a 3.5 km diameter (three times the maximum distance from shooting that displacement was detectable) could provide undisturbed foraging for the target species, minimizing compensatory feeding and further agricultural damage. Wildlife managers should, where possible, consider the fitness implications of shooting disturbance, and whether compensatory feeding and redistribution could hamper conflict mitigation. Management strategies should also include species‐specific monitoring and mitigation as we have demonstrated differing responses potentially due to imposed mitigation but also differing species ecology and “landscapes of fear.”
Balancing Objective Markers and Subjective Experience in Eating Disorder Diagnoses: Commentary on Dang et al. (2024)
Authors: Hagan Kelsey E. , Christensen Pacella Kara A. 
Published: October 2024

ABSTRACTThe results of Dang et al.'s recent systematic review and meta‐analysis suggested that individuals diagnosed with other specified feeding or eating disorder (OSFED) and those diagnosed with specified eating disorders (EDs, such as bulimia nervosa) endorse similar, elevated levels of ED‐related cognitions (but not behaviors). The DSM has traditionally conceptualized EDs primarily as disturbances in eating behavior, and the diagnostic boundaries for EDs are based on objective markers, such as behavioral frequencies and weight. Although focusing on objective markers for ED diagnoses and severity indices has advantages (e.g., clinical communication, measurement), pitfalls include diagnostic migration and low emphasis on ED cognitions. Dang et al.'s findings provide a basis for rethinking DSM's conceptualization of EDs as primarily behavioral. This commentary discusses the potential merits and challenges of emphasizing subjective cognitions when assigning ED diagnoses. We explore how objective markers (e.g., behavioral frequency, weight) and subjective experience (e.g., fear of weight gain) may be balanced to improve the clinical utility of ED diagnoses. In all, research that more deeply phenotypes the subjective experiences of people with EDs across contexts, identities, and cultures will enrich our understanding of eating pathology and may inform diagnostic revisions.
Taking a Deeper Dive Into OSFED Subtypes: A Meta‐Analysis and Systematic Review
Authors: Dang Thanh Ba , Hughes Elizabeth K. , Dang An Binh , Lai Heung Ying , Lee Jessica , Liu Shanshan , Portingale Jade , Fuller‐Tyszkiewicz Matthew , Krug Isabel 
Published: October 2024

ABSTRACTObjectiveTo compare all other specified feeding or eating disorders (OSFED) groups (atypical anorexia nervosa [AN], purging disorder [PD], night eating syndrome [NES], subthreshold bulimia nervosa [sub‐BN], and subthreshold binge‐eating disorder [sub‐BED]) to threshold eating disorders (EDs [AN, BN, and BED]) and control groups (CGs) on measures of eating and general psychopathology.MethodWe conducted a comprehensive search in PsycINFO, Medline, Embase, and CINAHL on all published studies from January 2013 to February 2024 using DSM‐5 diagnostic criteria via clinical interviews or well‐established diagnostic tools. We also undertook a quality appraisal using an adapted version of the Downs and Black criteria and registered the review with PROSPERO (ID: CRD42022314495).ResultsOverall, our meta‐analyses (n = 33 eligible studies) indicated that the combined OSFED and several specific OSFED subtypes displayed comparable levels of eating psychopathology to full‐threshold EDs. Our systematic review (n = 33 eligible studies) found individuals with OSFED to have comparable levels of eating and general psychopathology to full‐threshold EDs, but higher levels of eating and general psychopathology than CGs. These findings were specifically attributed to atypical AN and NES. There was a lack of evidence available for sub‐BN and sub‐BED. Studies mainly met the quality appraisal criteria. The main limitations identified in the included studies were insufficient reporting of their statistical power (78%) and no adjusting for potential confounding factors (67%).DiscussionFindings support the conceptualization of atypical AN, and NES as clinically significant EDs with similar severity to full‐threshold EDs.
Life History Strategies Drive Meso‐Scale Distribution Patterns in Coastal Benthic Macroinvertebrates
Authors: Gusha Molline Natanah C. , McQuaid Christopher D. 
Published: October 2024

ABSTRACTThe environment shapes the spatial distribution of species, but species also comprise suites of traits which may indicate their adaptability to a specific environment. This forms the basis of trait biogeography studies. We thus examined how a species distribution is not only influenced by its environment and traits, but by interactions among its traits. Trait information was collected for 150 intertidal macroinvertebrates along a 3000 km environmental and biogeographic gradient on the South African coast. This information was analysed, as functional entities (FEs) were species performing similar functions that have the same trait values and were further condensed into two trait domains (Reproduction and Lifestyle). We then defined Life History Strategies (LHS) as specific combinations of Lifestyle and Reproduction FEs. Seven combinations of Lifestyle and Reproduction formed LHS that dominated total biomass. Some of these LHS were ubiquitous, while others showed geographic patterns across our west‐east environmental gradient. For Lifestyle, filter‐feeders exhibited high abundances on the East (subtropical, oligotrophic) and West (cool‐temperate, eutrophic) extremes of the biogeographic gradient, but differed between the two in size at reproductive maturity and larval development type. This similarity in functionality of feeding mechanism and mobility with different reproductive strategies suggests a trait trade–off (investment in one trait reduces resources for others) between the Reproduction and Lifestyle domains. Within the Reproduction domain, gonochoristic, annual planktotrophic reproduction was common across bioregions, reflecting spin‐offs (investment in one trait facilitates another trait) among these traits. Gonochoristic investment in less frequent episodic reproduction is another trade‐off, with investment in large size and delayed maturation being a trade–off for many reproductive cycles. Overall, although our data supports the habitat templet model (i.e., the importance of environmental drivers), it further indicates that species distribution patterns observed along the South African coast reflect strong trait interactions and biomass patterns related to their LHS.
Taking knowledge exchange to practice: A scoping review of practical case studies to identify enablers of success in environmental management
Authors: Kapoor Tyreen , Cvitanovic Chris , Klenk Kimberly , Nguyen Vivian M 
Published: October 2024

AbstractA gap exists in the literature on how to implement theories of knowledge exchange (KE) into practice within an environmental management context. To support the improved practice of KE, we conducted a scoping literature review evaluating 56 empirical case studies globally to identify enabling conditions for implementing effective KE. Identified enabling conditions were organized into a core capacities framework, which highlighted essential elements of effective KE from organizational, individual, financial, material, practical, political, and social capacity dimensions. Results show that major enablers to effective KE relate to practitioners' individual and organizational capacity including the ability of practitioners (often boundary spanners) to establish trust with relevant actors through their interpersonal relationships and possessing sufficient background knowledge and skills to facilitate collaborations across disciplines and sectors. We also identified main challenges to engaging in KE (e.g., insufficient long‐ term funding for projects, lack of interpersonal skills for KE practitioners to build relationships and network, and inadequate background knowledge for practitioners to exchange knowledge in an accessible manner), and the outcomes and impacts that can emerge from effective KE work. We find that practitioners often perform quantitative evaluations that provide instantaneous and measurable impacts for the effectiveness of KE, but do not capture the impact of interpersonal relationships and trust that are best achieved through qualitative approaches. Lastly, the synthesis of enablers, challenges, outcomes, and impacts presented in this paper can be a resource for practitioners to identify what enablers may be missing from their KE strategies and in what capacity the KE work can be strengthened.
Novel Applications of CE‐ICP‐MS/MS: Monitoring of Antiaging GHK–Cu Cosmetic Component Encapsulation in Liposomes
Authors: Zajda Joanna , Wadych Emilia , Ogórek Karolina , Drozd Marcin , Matczuk Magdalena 
Published: October 2024

ABSTRACTThe hyphenation of the separation technique with the high‐sensitive mass spectrometry detection is one of the driving forces of modern analysis enabling measurements in complex matrices. In particular, capillary electrophoresis coupled to inductively coupled plasma tandem mass spectrometry allows for speciation analysis of selected analytes with a superior resolution. The mild, physiological‐friendly conditions of this separation technique offer the unique advantage of analyzing chemical entities in their intact form, which has been successfully exploited in various areas. Herein, we report the pioneering application of such a hyphenated technique in the cosmetic field to investigate the encapsulation of copper tripeptide complex (GHK–Cu) in liposomes. By monitoring copper and phosphorus signals, the formation of liposomes via a simple ethanol injection method was confirmed, and the concentration of GHK–Cu in the liposomes was assessed. The application of coupling of capillary electrophoresis with inductively coupled plasma tandem mass spectrometry (CE‐ICP‐MS/MS) in cosmetic studies could lead to the development of diverse liposomal formulations with preferential properties and expand their accessibility.
Investigation on the Effect of Persian Gum and Transglutaminase Enzyme on Some Physicochemical and Microstructural Characteristics of Low‐Fat Ultrafiltrated Iranian White Cheese
Authors: Habibi Seyedeh Ameneh , Jooyandeh Hossein 
Published: October 2024

ABSTRACTThis study aimed to assess the effect of Persian gum (PG) and microbial transglutaminase enzyme (MTGase) on some physicochemical and microstructural characteristics of low‐fat ultrafiltrated Iranian white cheese during 60 days of cold storage. To manufacture the low‐fat cheese samples, PG (0%, 0.25%, and 0.5%) and MTGase (0, 0.5 and 1 U/g of protein) were used and cheeses (low‐ and full‐fat) without PG and MTGase were considered as controls. The obtained results revealed that the treated samples with PG had a higher titratable acidity, moisture content, and moisture‐to‐protein ratio (M:P), but a lower protein content as compared to the low‐fat control (p ≤ 0.05). Furthermore, the cheese samples treated with the higher level of MTGase (i.e., 1 U/g of protein) had a higher protein and fat content (p ≤ 0.05). Methyl palmitate (C16:0) and methyl oleate (C18:1) were found to be the most abundant fatty acids in the tested cheeses. Additionally, scanning electron micrographs revealed that addition of PG and MTGase improved the microstructure of the samples, so that the sample containing 0.5 U enzyme and 0.5% gum was more similar to its full‐fat counterpart and obtained the highest overall acceptance score among the cheeses. Therefore, our findings revealed that with incorporation of PG and MTGase, a low‐fat ultrafiltrated white cheese could be produced with an appropriate functional, physicochemical, and microstructural characteristics comparable to the full‐fat product.
The Double Empathy Problem and Person‐Environment Fit: Mutual Understanding and Bidirectional Adjustment in Autistic Talent Acquisition
Authors: Drader‐Mazza Nicole , Lopez‐Kidwell Virginie , Kanwal Fizza , Reger Rhonda K. , Vogus Timothy J. 
Published: October 2024

ABSTRACTOrganizations are starting to actively invest in hiring initiatives aimed at recruiting autistic talent. However, given many of these initiatives are in their infancy, knowledge of autism and how best to assess and support autistic employees is low. Building on person‐environment fit (P‐E fit) theory and the double empathy problem, we examine how neurodiversity employment programs build mutual understanding and construct fit between autistic employees and their hiring organizations. We further explore the role of third‐party neurodivergent talent consultants (NTCs) in aiding these efforts during the birth stage of the cycle of talent. In Study 1, we use action research involving in‐depth structured interviews of participants (managers, coaches, and autistic employees) in a neurodiversity employment program at a major corporation in the financial services industry, supplemented with additional interviews of hiring managers and coaches with similar roles in other organizational settings. In Study 2, we collect qualitative survey data from autistic adults participating in other neurodiversity employment programs. Using these data, we explicate the practices that remove barriers to autistic employment and processes of ongoing coaching and support from NTCs that build and manage the double empathy problem by enhancing mutual understanding and increasing the perceptions of fit. We find that NTCs facilitate the acquisition of autistic talent through revised job search and recruitment (e.g., tailored job descriptions), alternative screening procedures (e.g., hands‐on assessments), and supported socialization and onboarding (e.g., communication, networking).
Genomic adaptation of Clostridium perfringens to human intestine
Authors: Wu Ke , Wang Juan , Yan Zelin , Zhu Yanyan , Wang Shaolin , Fu Bo , Sun Chengtao , Li Ruichao , Fox Edward M. , Fanning Séamus , Bai Li , Wang Yang , Tang Yizhi , Yin Zhe , Zhang Rong , Wang Hongning 
Published: October 2024

AbstractClostridium perfringens is often associated with foodborne diseases, posing significant public health risks. However, genomic investigation of C. perfringens isolates from the human population has been lacking. This study aims to fill this knowledge gap by examining the genomic characteristics of C. perfringens isolates from 699 individuals at a provincial hospital in China. We further conducted evolutionary and pan‐genomic analyses, incorporating isolates from humans and animals worldwide. The results reveal potential regional and transregional transmission of C. perfringens among individuals, along with the common transfer of small gene clusters during this process. Notably, the food poisoning‐associated toxin gene cpe was identified in a fusion plasmid for the first time in an isolate, indicating fusion of pCP13‐like and pCW3‐like plasmids and the potential for transfer of cpe across genetic backgrounds. Moreover, we observed that the genomic characteristics of C. perfringens correlate with host species, with specific toxin genes, such as pfoA and colA, potentially influencing host selectivity. Through this comprehensive genomic analysis, we provide novel insights into the fusion of pCW3‐like and pCP13‐like plasmids, the genetic location of cpe, the transmission dynamics of C. perfringens strains, and the relationship between toxin genes and host relevance. These findings expand our understanding of C. perfringens and its implications for public health.
Prognostic Value of Systemic Inflammation, Nutritional Status and Sarcopenia in Patients With Amyotrophic Lateral Sclerosis
Authors: Zhu Yahui , Zhang Ying , Li Mao , Bai Jiongming , Wang Hongfen , Pang Xinyuan , Du Rongrong , Wang Jiao , Huang Xusheng 
Published: October 2024

ABSTRACTBackgroundNutritional status, systemic inflammatory responses and muscle mass are associated with the prognosis of patients with amyotrophic lateral sclerosis (ALS). However, the optimal biomarker for predicting prognosis remains unclear. This study aimed to identify the optimal indicators of survival among the nutrition‐based, inflammation‐based and muscle mass–related markers for ALS patients.MethodsWe enrolled ALS patients from January 2014 to December 2019. Experienced neurologists followed up with the participants until January 2022. This study included a total of 17 nutritional, systemic inflammatory or muscle mass–related indicators. Maximally selected rank statistics determined the cut‐off points for these indicators. Kaplan–Meier estimation was used to assess survival. Uni‐ and multivariate Cox proportional hazards models were used to determine the effects of indicators on survival. Finally, time‐dependent receiver operating characteristic (time‐ROC) curves and the C‐index were calculated to evaluate the predictive efficacy of different indicators.ResultsA total of 506 patients with ALS were enrolled in this study, including 288 males (56.9%) and 218 females (43.1%), with a mean age of 54.2 ± 10.5 years. Among these ALS patients, 334 cases (68.0%) either died or underwent tracheotomy. In univariate Cox proportional hazards regression, 11 indicators were significantly associated with ALS survival (p < 0.05). And systemic immune inflammation (SII), platelet‐to‐lymphocyte ratio (PLR), modified geriatric nutritional risk index (mGNRI), creatinine and sarcopenia index (SI, (creatinine/cystatin C) × 100) were determined as independent predictors (p < 0.05) in multivariate Cox proportional hazards regression. A higher SI predicted longer survival (hazard ratio, 0.59; 95% confidence interval [CI], 0.46–0.76; p < 0.001). The results of time‐ROC and C‐index analyses indicated that SI had the best predictive efficacy for ALS survival, with a C‐index of 0.65 (95% CI, 0.54–0.75) for 1‐year, 0.61 (95% CI, 0.57–0.65) for 3‐year and 0.59 (95% CI, 0.55–0.62) for 5‐year survival. Across different subgroups, SI had the highest C‐index in men and women, limb onset and aged < 60 year ALS patients, compared with other indicators. However, cystatin C was the best indicator for predicting the survival of ALS patients with bulbar onset, whereas the prognostic nutritional index (PNI) was the best for those aged ≥60 years.ConclusionsThe serum SI demonstrates superior prognostic ability compared to other inflammation‐based, nutrition‐based and muscle mass–related indicators for patients with ALS. Given its simplicity and availability, it is well suited for clinical use in evaluating the prognosis of ALS patients.