bluuebunny/crossref_metadata_2025_split huggingface dataset:
Report of the Assay Guidance Workshop on 3-Dimensional Tissue Models for Antiviral Drug Development
Authors: Jordan Robert , Ford-Scheimer Stephanie L , Alarcon Rodolfo M , Atala Anthony , Borenstein Jeffrey T , Brimacombe Kyle R , Cherry Sara , Clevers Hans , Davis Mindy I , Funnell Simon G P , Gehrke Lee , Griffith Linda G , Grossman Abigail C , Hartung Thomas , Ingber Donald E , Kleinstreuer Nicole C , Kuo Calvin J , Lee Emily M , Mummery Christine L , Pickett Thames E , Ramani Sasirekha , Rosado-Olivieri Edwin A , Struble Evi B , Wan Zhengpeng , Williams Mark S , Hall Matthew D , Ferrer Marc , Markossian Sarine 
Published: September 2023

Abstract
The National Center for Advancing Translational Sciences (NCATS) Assay Guidance Manual (AGM) Workshop on 3D Tissue Models for Antiviral Drug Development, held virtually on 7–8 June 2022, provided comprehensive coverage of critical concepts intended to help scientists establish robust, reproducible, and scalable 3D tissue models to study viruses with pandemic potential. This workshop was organized by NCATS, the National Institute of Allergy and Infectious Diseases, and the Bill and Melinda Gates Foundation. During the workshop, scientific experts from academia, industry, and government provided an overview of 3D tissue models’ utility and limitations, use of existing 3D tissue models for antiviral drug development, practical advice, best practices, and case studies about the application of available 3D tissue models to infectious disease modeling. This report includes a summary of each workshop session as well as a discussion of perspectives and challenges related to the use of 3D tissues in antiviral drug discovery.
Homodimeric Granzyme A Opsonizes Mycobacterium tuberculosis and Inhibits Its Intracellular Growth in Human Monocytes via Toll-Like Receptor 4 and CD14
Authors: Rasi Valerio , Phelps Kathleen R , Paulson Keegan R , Eickhoff Christopher S , Chinnaraj Mathivanan , Pozzi Nicola , Di Gioia Marco , Zanoni Ivan , Shakya Shubha , Carlson Haley L , Ford David A , Kolar Grant R , Hoft Daniel F 
Published: September 2023

Abstract
Mycobacterium tuberculosis (Mtb)-specific γ9δ2 T cells secrete granzyme A (GzmA) protective against intracellular Mtb growth. However, GzmA-enzymatic activity is unnecessary for pathogen inhibition, and the mechanisms of GzmA-mediated protection remain unknown. We show that GzmA homodimerization is essential for opsonization of mycobacteria, altered uptake into human monocytes, and subsequent pathogen clearance within the phagolysosome. Although monomeric and homodimeric GzmA bind mycobacteria, only homodimers also bind cluster of differentiation 14 (CD14) and Toll-like receptor 4 (TLR4). Without access to surface-expressed CD14 and TLR4, GzmA fails to inhibit intracellular Mtb. Upregulation of Rab11FIP1 was associated with inhibitory activity. Furthermore, GzmA colocalized with and was regulated by protein disulfide isomerase AI (PDIA1), which cleaves GzmA homodimers into monomers and prevents Mtb inhibitory activity. These studies identify a previously unrecognized role for homodimeric GzmA structure in opsonization, phagocytosis, and elimination of Mtb in human monocytes, and they highlight PDIA1 as a potential host-directed therapy for prevention and treatment of tuberculosis, a major human disease.
Synergy between amikacin andProtium heptaphyllumessential oil against polymyxin resistanceKlebsiella pneumoniae
Authors: de Melo Andressa L F , Rossato Luana , Veloso Tácia C , Cardoso Cláudia A L , Velasques Jannaína , Simionatto Simone 
Published: September 2023

AbstractAimsWe investigated the chemical composition and the in vitro and in vivo antibacterial effects of Protium heptaphyllum essential oil (PHEO) alone and in combination with antibiotics against polymyxin-resistant Klebsiella pneumoniae isolates.Methods and resultsHydrodistillation was used to obtain PHEO, and gas chromatography coupled with mass spectrometry revealed α-pinene, δ-3-carene, and β-pinene as major components present in PHEO. Minimum inhibitory concentration was determined using the broth microdilution technique and ranged from 256 to 512 µg ml−1. The checkerboard method showed synergy with the combination of PHEO and amikacin (AMK) against the polymyxin-resistant K. pneumoniae isolates. In 8 of the 10 isolates tested, the fractional inhibitory concentration indexes (FICIs) ranged from 0.06 to 0.5, while in the remaining two isolates, the combination exerted an additive effect (FICI of 0.6 and 1.0), resulting in AMK dose reduce of range 2- to 16-fold, in the presence of PHEO. Analysis using zero interaction potency revealed high synergy score (63.9). In the in vivo assay, the survival of Caenorhabditis elegans was significantly improved in the presence of PHEO (1 µg ml−1) + AMK (µg ml−1) combination as compared to 32 µg ml−1 AMK alone. Furthermore, PHEO concentrations of 256 and 512 µg ml−1 were found to be non-toxic on the experimental model.ConclusionTo our knowledge, this is the first report of such type of synergism demonstrating an antimicrobial effect against polymyxin-resistant K. pneumoniae isolates.
Baru (Dipteryx alata Vog.) agro-industrial by-products promote the growth and metabolism of probiotic strains
Authors: Alves-Santos Aline M , Silva Monik Mariele A , Lima Marcos S , Souza Evandro L , Naves Maria Margareth V 
Published: September 2023

Abstract

Aims
To evaluate the phytochemical composition and effects of the baru peel and pulp (BPP) and the partially defatted baru nut (DBN) on the growth and metabolism of probiotics.

Methods and results
The proximate composition, including dietary fibers, and polyphenol profile were determined in the BPP and DBN, and the prebiotic activity was evaluated on the growth and metabolism of the Lactobacillus and Bifidobacterium strains. BPP and DBN have a high content of insoluble fibers and phenolic compounds, mainly flavonoids and phenolic acids. Moreover, DBN stands out for its high content of proteins and lipids. BPP and DBN stimulated the growth and metabolism of Bifidobacterium animalis subsp. lactis BB-12, Lactobacillus acidophilus LA-05, and Lacticaseibacillus casei L-26.

Conclusions
Baru by-products have potential prebiotic properties to be confirmed in preclinical and clinical studies, and to be explored as an ingredient in new health-promoting foods.

Impact Statement
Agro-industrial baru wastes, the peel plus pulp and the partially defatted nut, are sources of health-promoting compounds and stimulate the growth and metabolism of probiotics, indicating prebiotic properties.
Effect of the essential amino acid-nitrogen to total nitrogen ratio on lysine requirement for nitrogen retention in growing pigs
Authors: Camiré Carley M , Wellington Michael O , Panisson Josiane C , Rodrigues Lucas A , Shoveller Anna K , Columbus Daniel A 
Published: September 2023

Abstract
Low protein diets supplemented with essential amino acids (EAA) fed to pigs reduce the excess supply of EAA and nitrogen (N). However, low protein diets may become limiting in non-essential amino acids (NEAA) and N, thus affecting the utilization of EAA for N retention. It has been suggested that the EAA-N:total N (E:T) ratio can give an indication of dietary N sufficiency. An N-balance study was conducted to determine the effect of E:T ratio on the Lys requirement for maximum N retention. A total of 80 growing barrows (19.3 ± 0.21 kg initial body weight) were randomly assigned to 1 of 10 diets (n = 8) in 8 blocks in a 2 × 5 factorial arrangement. Diets consisted of a low ratio (LR; E:T of 0.33) or a high ratio (HR; E:T of 0.36) with graded Lys content (0.82%, 0.92%, 1.02%, 1.12%, and 1.22% standardized ileal digestible [SID]). After a 7-d adaptation, a 4-d N-balance collection was conducted. Blood samples were obtained on d 2 of the collection period 2 h after the morning meal for plasma urea N (PUN) analysis. Data were analyzed using the MIXED model procedure with fixed effects of ratio (n = 2), Lys (n = 5), and their interactions. The experimental block (room) was included as a random effect (n = 8). The SID Lys requirement was estimated using PROC NLIN linear broken-line breakpoint model. There was a significant interaction between E:T ratio and Lys (P &lt; 0.01), where LR diets had a higher N retention than HR diets, while increasing Lys linearly increased N retention (P = 0.01) in both HR and LR diets. The marginal efficiency of utilizing SID Lys (P &lt; 0.01) reduced with increasing Lys content, while the efficiency of utilizing N (P &lt; 0.05) increased as Lys increased. The SID Lys required to maximize N retention of pigs fed HR diets was estimated at 1.08% (R2 = 0.61) and LR diets at 1.21% (R2 = 0.80). The current results indicate that N may be limiting in diets with a high E:T ratio, limiting N retention. Supplying additional dietary N, as intact protein, can increase N retention, resulting in a greater Lys requirement.
Mitragynine in the Orange County DUID population
Authors: Kedzierski Nancy , Mata Dani 
Published: September 2023

Abstract
In recent years, mitragynine has been consistently detected in driving under the influence of drug (DUID) cases. In this paper, we evaluate 3 years (2017–2019) worth of DUID data from arrested drivers in Orange County, CA, USA. From the 25,398 DUID cases received in those 3 years, there were 60 (0.24%) cases with detectable concentrations, &gt;10 ng/mL, of mitragynine. The majority of drivers were male (90%) and were stopped during the week (81%), considered Monday 0000 to Friday 1159. The concentration range for all mitragynine cases was 10.5–960 ng/mL, with a mean of 109 ng/mL and a median of 58 ng/mL. Forty four of the 60 cases were also screened for 7-hydroxymitragynine, and 27 (63%) were positive. The police reports and drug recognition expert evaluations were collected and evaluated. No case contained solely mitragynine, and the most common drugs detected in combination were central nervous system depressants (ethanol, followed by benzodiazepines), stimulants (methamphetamine and cocaine) and opioids (fentanyl and indication of heroin). Two cases containing only one other psychoactive substance are discussed more thoroughly to attempt to identify the contributions of mitragynine to driving impairment. Collected demographic, toxicological and field observations are presented for all cases.
The 2023 Impact of Inflammatory Bowel Disease in Canada: Indirect (Individual and Societal) and Direct Out-of-Pocket Costs
Authors: Kuenzig M Ellen , Im James H B , Coward Stephanie , Windsor Joseph W , Kaplan Gilaad G , Murthy Sanjay K , Benchimol Eric I , Bernstein Charles N , Bitton Alain , Jones Jennifer L , Lee Kate , Peña-Sánchez Juan-Nicolás , Rohatinsky Noelle , Ghandeharian Sara , Jones May Tyrel , Tabatabavakili Sahar , Jogendran Rohit , Weinstein Jake , Khan Rabia , Hazan Elias , Browne Mira , Davis Tal , Goddard Quinn , Gorospe Julia , Latos Kate , Mason Kate , Kerr Jack , Balche Naji , Sklar Anna , Targownik Laura E 
Published: September 2023

Abstract
People living with inflammatory bowel disease (IBD) and their caregivers are faced with indirect and out-of-pocket costs that they would not otherwise experience. These costs impact one’s ability to contribute to the economy to their fullest potential. The indirect costs of IBD in Canada are estimated to be at least $1.51 billion in 2023 and include costs associated with lost productivity resulting from a combination of missed work (absenteeism), decreased workplace productivity (presenteeism), unemployment, premature mortality, and caregiving costs. Unemployment is the largest contributor to indirect costs ($1.14 billion), followed by costs of absenteeism and presenteeism ($285 million). Caregiving costs for children with IBD are estimated to be nearly $58 million. Canadians with IBD also pay $536 million every year for care that is not covered by universal or supplemental private health insurance; this includes allied healthcare (e.g., care provided by psychologists), medication, and other supportive therapy. Combined, the indirect and out-of-pocket costs of IBD in Canada are estimated at more than $2 billion CAD in 2023. This is substantially higher than the estimate of $1.29 billion in Crohn’s and Colitis Canada’s 2018 Impact of IBD report with differences attributable to a combination of rising prevalence, inflation, and the addition of presenteeism and caregiving costs to the total indirect costs.
The 2023 Impact of Inflammatory Bowel Disease in Canada: Special Populations—IBD in Seniors
Authors: Shaffer Seth R , Kuenzig M Ellen , Windsor Joseph W , Bitton Alain , Jones Jennifer L , Lee Kate , Murthy Sanjay K , Targownik Laura E , Peña-Sánchez Juan-Nicolás , Rohatinsky Noelle , Ghandeharian Sara , Tandon Parul , St-Pierre Joëlle , Natt Navneet , Davis Tal , Weinstein Jake , Im James H B , Benchimol Eric I , Kaplan Gilaad G , Goddard Quinn , Gorospe Julia , Bergevin Maxime , Silver Ken , Bowles Dawna , Stewart Margaret , Pearlstein Marsha , Dawson Elizabeth H , Bernstein Charles N 
Published: September 2023

Abstract
Approximately one out of every 88 seniors has inflammatory bowel disease (IBD), and this is expected to increase in the future. They are more likely to have left-sided disease in ulcerative colitis, and isolated colonic disease in Crohn’s disease; perianal disease is less common. Other common diagnoses in the elderly must also be considered when they initially present to a healthcare provider. Treatment of the elderly is similar to younger persons with IBD, though considerations of the increased risk of infections and malignancy must be considered when using immune modulating drugs. Whether anti-TNF therapies increase the risk of infections is not definitive, though newer biologics, including vedolizumab and ustekinumab, are thought to be safer with lower risk of adverse events. Polypharmacy and frailty are other considerations in the elderly when choosing a treatment, as frailty is associated with worse outcomes. Costs for IBD-related hospitalizations are higher in the elderly compared with younger persons. When elderly persons with IBD are cared for by a gastroenterologist, their outcomes tend to be better. However, as elderly persons with IBD continue to age, they may not have access to the same care as younger people with IBD due to deficiencies in their ability to use or access technology.
Guarding success of the rarest sex in the amphipodHyalella aztecaSaussure, 1858 (Amphipoda: Hyalellidae)
Authors: Beristain-Castillo Evelyn , Salazar-Bautista José L , Moyaho Alejandro 
Published: September 2023

AbstractTraditional methods to study precopulatory mate guarding in Hyalella azteca (Saussure, 1858) have some limitations because precopulatory pairs are usually observed in isolation. This condition precludes researchers from testing the role of the social environment in the duration of precopulatory mate guarding. We present the use of a sampling method to investigate the influence of sex ratios on guarding success (the proportion of precopulatory pairs per trial) in mixed-sex groups of H. azteca. The presence/absence of precopulatory pairs over eight consecutive days, morning and afternoon samplings, was analysed as a series of successes (runs) to estimate the mean precopula duration. The non-random nature of the observed duration of the precopula was tested against a probabilistic distribution based on the set of all ways every possible duration may occur. While skewed sex ratios increased guarding success of the rarest sex, even sex ratios decreased it. The mean duration of observed precopulas (2.32 and 2.08 d for the morning and afternoon periods, respectively) is consistent with theoretical and empirical results, which confirms the accuracy and usefulness of the sampling method we used. The use of this method and the associated probabilistic analysis of the relevant data can enhance the study of the effect of biotic and abiotic factors on precopulatory mate guarding. It can also be used to test predictions derived from hypothesis concerned with mate guarding among crustaceans.
Tracing the opposing assimilate and nutrient flows in live conifer needles
Authors: Gao Chen , Marker Sean J V , Gundlach Carsten , Poulsen Henning F , Bohr Tomas , Schulz Alexander 
Published: September 2023

Abstract
The vasculature along conifer needles is fundamentally different from that in angiosperm leaves as it contains a unique transfusion tissue inside the bundle sheath. In this study, we used specific tracers to identify the pathway of photoassimilates from mesophyll to phloem, and the opposing pathway of nutrients from xylem to mesophyll. For symplasmic transport we applied esculin to the tip of attached pine needles and followed its movement down the phloem. For apoplasmic transport we let detached needles take up a membrane-impermeable contrast agent and used micro-X-ray computed tomography to map critical water exchange interfaces and domain borders. Microscopy and segmentation of the X-ray data enabled us to render and quantify the functional 3D structure of the water-filled apoplasm and the complementary symplasmic domain. The transfusion tracheid system formed a sponge-like apoplasmic domain that was blocked at the bundle sheath. Transfusion parenchyma cell chains bridged this domain as tortuous symplasmic pathways with strong local anisotropy which, as evidenced by the accumulation of esculin, pointed to the phloem flanks as the preferred phloem-loading path. Simple estimates supported a pivotal role of the bundle sheath, showing that a bidirectional movement of nutrient ions and assimilates is feasible and emphasizing the role of the bundle sheath in nutrient and assimilate exchange.
Study of the diagnostic efficiency of anti-ZnT8 autoantibodies for type 1 diabetes in pediatric patients
Authors: Fuentes-Cantero Sandra , González-Rodríguez Concepción , Rodríguez-Chacón Carmen , Galvan-Toribio Raquel , Hermosín-Escudero Joaquín , Pérez-Pérez Antonio , León-Justel Antonio 
Published: September 2023

Abstract

Objective
Zinc transporter 8 autoantibodies (ZNt8A) are 1 of the 4 main autoantibodies used for the diagnosis of type 1 diabetes (T1D), with glutamic acid decarboxylase autoantibodies (GADA), islet antigen-2 autoantibodies (IA-2A), and insulin autoantibodies (IAA). The objective of this study is to evaluate the diagnostic efficiency of these autoantibodies for the diagnosis of T1D in pediatric patients.

Methods
A retrospective analysis of patients under 16 years of age with suspected T1D was made between June 2020 and January 2021. A total of 80 patients were included in the study, with 1 sample per patient. Subjects were classified according to diagnosis.

Results
Of the subjects included in the study, 50 developed T1D. The diagnostic efficacy was IA-2A (cutoff ≥ 28 U/L) sensitivity 0.26 (95% CI: 0.14-0.38) and specificity 0.97 (95% CI: 0.79-1.0); GADA (cutoff ≥ 17 U/mL) sensitivity 0.40 (95% CI: 0.26-0.54) and specificity 0.87 (95% CI: 0.75-0.99); ZnT8A (cut off ≥ 15 U/L) sensitivity 0.62 (95% CI: 0.49-0.75) and specificity 0.97 (95% CI: 0.90-1.0). ZnT8A obtained the most significantly global diagnostic accuracy (0.75), and GADA with ZnT8A showed the highest correlation.

Conclusion
The results obtained indicate a higher efficiency of anti-ZnT8 autoantibodies for the diagnosis of T1D in pediatric patients. Clinical efficiency of diabetic autoantibodies is method and assay dependent and influences combined diagnostic strategies.
Petrus Biverus’s Sacrum Oratorium and Sacrum Sanctuarium (Antwerp, 1634): Balthasar Moretus’s Preference for Pearls over Glass
Authors: Imhof Dirk 
Published: September 2023

Abstract
In the first half of the seventeenth century the Plantin-Moretus Press of Antwerp was widely known for the high quality of its editions. One such case are two editions composed by the Spanish Jesuit Petrus Biverus published in 1634, namely: the Sacrum Oratorium piarum imaginum immaculatae Mariae and the Sacrum sanctuarium crucis. Both publications are well known for their numerous illustrations and as noteworthy emblem books. Nevertheless, correspondence between Moretus and Biverus reveals that Biverus was displeased with the high selling price of his books, while Moretus’s responses to Biverus’s remarks provide a rare view of how he envisioned his work as a publisher. In this article, I discuss this tension between the production costs and the author’s expectations. Like many other Jesuit authors, Biverus forgot that a publisher’s aim was to make a profit; Moretus forgot that authors want to have their books read and known by as many readers as possible.
The B-type Binaries Characterisation Programme – II. VFTS 291: a stripped star from a recent mass transfer phase
Authors: Villaseñor J I , Lennon D J , Picco A , Shenar T , Marchant P , Langer N , Dufton P L , Nardini F , Evans C J , Bodensteiner J , de Mink S E , Götberg Y , Soszyński I , Taylor W D , Sana H 
Published: September 2023

ABSTRACT
Recent studies of massive binaries with putative black hole companions have uncovered a phase of binary evolution that has not been observed before, featuring a bloated stripped star that very recently ceased transferring mass to a main-sequence companion. In this study, we focus on the candidate system VFTS 291, a binary with an orbital period of 108 d and a high semi-amplitude velocity (K1 = 93.7 ± 0.2 km s−1). Through our analysis of the disentangled spectra of the two components, together with dynamical and evolutionary arguments, we identify a narrow-lined star of ∼1.5–2.5 $\, \mathrm{M}_\odot$ dominating the spectrum, and an early B-type main-sequence companion of 13.2 ± 1.5 $\, \mathrm{M}_\odot$. The low mass of the narrow-lined star, and the high mass ratio, suggest that VFTS 291 is a post-mass-transfer system, with the narrow-lined star being bloated and stripped of its hydrogen-rich envelope, sharing many similarities with other recently discovered stripped stars. Our finding is supported by our detailed binary evolution models, which indicate that the system can be well explained by an initial configuration consisting of an 8.1 $\, \mathrm{M}_\odot$ primary with an 8 $\, \mathrm{M}_\odot$ companion in a 7 d orbital period. While some open questions remain, particularly concerning the surface helium enrichment of the stripped star and the rotational velocity of the companion, we expect that high-resolution spectroscopy may help reconcile our estimates with theory. Our study highlights the importance of multi-epoch spectroscopic surveys to identify and characterize binary interaction products, and provides important insights into the evolution of massive binary stars.