bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enzymatic glycosylation of aloesone performed by plant UDP-dependent glycosyltransferases
Authors: Putkaradze Natalia , Dato Laura , Kırtel Onur , Hansen Jørgen , Welner Ditte Hededam 
Published: July 2024

Abstract
Aloesone is a bioactive natural product and biosynthetic precursor of rare glucosides found in rhubarb and some aloe plants including Aloe vera. This study aimed to investigate biocatalytic aloesone glycosylation and more than 400 uridine diphosphate-dependent glycosyltransferase (UGT) candidates, including multifunctional and promiscuous enzymes from a variety of plant species were assayed. As a result, 137 selective aloesone UGTs were discovered, including four from the natural producer rhubarb. Rhubarb UGT72B49 was further studied and its catalytic constants (kcat = 0.00092 ± 0.00003 s−1, KM = 30 ± 2.5 μM) as well as temperature and pH optima (50 °C and pH 7, respectively) were determined. We further aimed to find an efficient aloesone glycosylating enzyme with potential application for biocatalytic production of the glucoside. We discovered UGT71C1 from Arabidopsis thaliana as an efficient aloesone UGT showing a 167-fold higher catalytic efficiency compared to that of UGT72B49. Interestingly, sequence analysis of all the 137 newly identified aloesone UGTs showed that they belong to different phylogenetic groups, with the highest representation in groups B, D, E, F and L. Finally, our study indicates that aloesone C-glycosylation is highly specific and rare, since it was not possible to achieve in an efficient manner with any of the 422 UGTs assayed, including multifunctional GTs and 28 known C-UGTs.
Why Patents on Climate Technologies Must Be Cut Short
Authors: Van Dycke Lodewijk 
Published: July 2024

Abstract
This contribution questions the term of protection for patents under circumstances of climate change. Patents typically last for 20 years but, for climate-related technologies, this is arguably too long. Under the 1.5°C scenario of the Paris Agreement, we need to make significant headway before 2030. Luckily, the technologies that need to be implemented broadly to reach the 2030 threshold have been developed already. To save civilisation from the worst impacts of climate change, the roll-out of existing technologies (static efficiency) is more important than the development of new ones (dynamic efficiency).
However, patent terms take neither static efficiency nor the climate timeframe into account. Technologies developed today will come off patent only in the 2040s, limiting their free availability when their wide roll-out should be the main concern. Conversely, the climate technologies that come off patent today were developed in the early 2000s, long before climate change acquired its current urgency and investment in climate technologies was ramped up.
These developments show that innovation systems for climate change have worked well, but they also show how terms of protection may now curtail the usefulness of past innovations. The contribution will analyse patent terms from a domestic and an international political economy perspective. The contribution will argue that, on balance, the situation requires a change of the TRIPS Agreement to shorten the term of patents on mature climate technologies. The TRIPS-waiver for patents on COVID-19 vaccines provides a partial precedent.
Siderophore interactions drive the ability of Pseudomonas spp. consortia to protect tomato against
Ralstonia solanacearum
Authors: Shao Zhengying , Gu Shaohua , Zhang Xiaoni , Xue Jiao , Yan Tao , Guo Saisai , Pommier Thomas , Jousset Alexandre , Yang Tianjie , Xu Yangchun , Shen Qirong , Wei Zhong 
Published: July 2024

Abstract
The soil-borne bacterial pathogen Ralstonia solanacearum causes significant losses in Solanaceae crop production worldwide, including tomato, potato, and eggplant. To efficiently prevent outbreaks, it is essential to understand the complex interactions between pathogens and the microbiome. One promising mechanism for enhancing microbiome functionality is siderophore-mediated competition, which is shaped by the low iron availability in the rhizosphere. This study explores the critical role of iron competition in determining microbiome functionality and its potential for designing high-performance microbiome engineering strategies. We investigated the impact of siderophore-mediated interactions on the efficacy of Pseudomonas spp. consortia in suppressing R. solanacearum, both in vitro and in vivo. Our findings show that siderophore production significantly enhances the inhibitory effects of Pseudomonas strains on pathogen growth, while other metabolites are less effective under iron-limited conditions. Moreover, siderophores play a crucial role in shaping interactions within the consortia, ultimately determining the level of protection against bacterial wilt disease. This study highlights the key role of siderophores in mediating consortium interactions and their impact on tomato health. Our results also emphasize the limited efficacy of other secondary metabolites in iron-limited environments, underscoring the importance of siderophore-mediated competition in maintaining tomato health and suppressing disease.
Energetic Costs of Stress in Developing Fishes: Quantifying Allostasis and Allostatic Load
Authors: Hunt von Herbing Ione 
Published: July 2024

Synopsis
Stress exerts negative effects on fish health through stimulation of the hypothalamic-pituitary-interrenal axis and autonomic nervous system, resulting in heightened neural and neuroendocrine responses. Energetic investment and physiological adaptation are then required to re-establish homeostatic stability or reach a new allostatic state. The cost of the energetic investment is referred to as allostatic load (AL). While determining the sources of stress and assessing their consequences have resulted in estimates of AL, most of this work has been conducted in adult mammals and humans; no ALs exist for developing fish. From a series of experiments on a model species, zebrafish (Danio rerio), whose yolk-sac larvae were exposed to two chronic stressors (high-temperature and hypoxia), ALs were quantified based on biomarkers of ontogenetic changes in growth, morphometrics, and metabolic activities. Results showed that for zebrafish yolk-sac larvae, chronic stress imposed high AL and, thus, high total allostatic energetic costs, (Rt (AL)), because of prolonged energy demand in the face of limited resources (e.g., yolk). Under severe chronic stress, energetic costs were sufficiently large that energy-limited developing fish may not be able to fully compensate, resulting in maladaptive responses from allostatic overload, leading either to death or to novel allostatic states, possibly more resilient to environmental change.
The surgical outcome of standard lobectomy versus sleeve lobectomy in patients with non-small cell lung cancer: propensity score matching
Authors: Ülker Melike , Ağkoç Melek , Amirov Fahmin , Duman Salih , Özkan Berker , Erelel Mustafa , Kara Murat , Toker Alper 
Published: July 2024

Abstract

OBJECTIVES
The goal of this study was to compare the patients who underwent standard or sleeve lobectomy for non-small cell lung cancer in terms of postoperative outcomes, prognostic factors and overall survival.

METHODS
Between January 2002 and January 2020, the patients with squamous cell carcinoma or adenocarcinoma who underwent standard lobectomy or sleeve lobectomy by thoracotomy in our clinic were analysed retrospectively. Standard and sleeve groups were compared after propensity score matching in terms of age, comorbidity, T status, N status and pathological stage. Primary outcomes were morbidity and mortality; the secondary outcome was overall survival.

RESULTS
The study included 476 patients, and sleeve lobectomy was performed in 196 (41.1%) patients. Multivariable analysis revealed that age over 61 years (P = 0.003 and P = 0.005, respectively), forced expiratory volume in 1 s (FEV1) below 84% (P = 0.013 and P = 0.205, respectively) and the presence of perineural invasion (P = 0.052 and P = 0.001, respectively) were poor prognostic factors in the standard lobectomy and the sleeve groups. The propensity matching analysis included 276 patients (138 sleeve lobectomy and 138 standard lobectomy). Complications occurred in 96 (69.6%) and 92 (66.7%) patients in the standard and sleeve groups, respectively (P = 0.605). Three (2.2%) patients in the standard group and 5 (3.6%) patients in the sleeve group died within 90 days postoperatively (P = 0.723).

CONCLUSIONS
Bronchial sleeve lobectomy is a safe procedure that can be applied in oncologically suitable cases without causing higher mortality than a standard lobectomy.
Inverse probability weighting for self-selection bias correction in the investigation of social inequality in mortality
Authors: Petersen Gitte Lindved , Jørgensen Terese Sara Høj , Mathisen Jimmi , Osler Merete , Mortensen Erik Lykke , Molbo Drude , Hougaard Charlotte Ørsted , Lange Theis , Lund Rikke 
Published: July 2024

Abstract

Background
Empirical evaluation of inverse probability weighting (IPW) for self-selection bias correction is inaccessible without the full source population. We aimed to: (i) investigate how self-selection biases frequency and association measures and (ii) assess self-selection bias correction using IPW in a cohort with register linkage.

Methods
The source population included 17 936 individuals invited to the Copenhagen Aging and Midlife Biobank during 2009–11 (ages 49–63 years). Participants counted 7185 (40.1%). Register data were obtained for every invited person from 7 years before invitation to the end of 2020. The association between education and mortality was estimated using Cox regression models among participants, IPW participants and the source population.

Results
Participants had higher socioeconomic position and fewer hospital contacts before baseline than the source population. Frequency measures of participants approached those of the source population after IPW. Compared with primary/lower secondary education, upper secondary, short tertiary, bachelor and master/doctoral were associated with reduced risk of death among participants (adjusted hazard ratio [95% CI]: 0.60 [0.46; 0.77], 0.68 [0.42; 1.11], 0.37 [0.25; 0.54], 0.28 [0.18; 0.46], respectively). IPW changed the estimates marginally (0.59 [0.45; 0.77], 0.57 [0.34; 0.93], 0.34 [0.23; 0.50], 0.24 [0.15; 0.39]) but not only towards those of the source population (0.57 [0.51; 0.64], 0.43 [0.32; 0.60], 0.38 [0.32; 0.47], 0.22 [0.16; 0.29]).

Conclusions
Frequency measures of study participants may not reflect the source population in the presence of self-selection, but the impact on association measures can be limited. IPW may be useful for (self-)selection bias correction, but the returned results can still reflect residual or other biases and random errors.
Constitutionalizing Protection for Refugee Women and Girls in South Asia
Authors: Shanker Roshni 
Published: July 2024

Abstract
The South Asian region remains an epicentre of forced migration. Women comprise about half the region’s refugee population, and many are traumatized by sexual and gender-based violence (SGBV) experienced in their countries of origin and during flight. The 1951 Refugee Convention is not well ratified in the region and few States have developed domestic asylum laws, relying instead on ad hoc policies, core rule of law principles, and constitutional provisions to facilitate refugees’ access to essential legal protections. Many refugees in South Asia do not have a clear legal status, which can exacerbate rights violations, including SGBV. Over the years, through judicial activism, courts have developed a layered refugee law jurisprudence relying on criminal justice principles, executive orders, corresponding laws, and key international human rights treaties. These efforts have been complemented by the evolution of several formal and informal systems at the grassroots level, such as community-based dispute resolution mechanisms and State-run legal aid services, which have allowed refugee women and girls to access justice systems and seek redress. This article examines the legal strategies adopted by courts in Bangladesh, Pakistan, and India to uphold the rights of refugee women and girls and to protect survivors of SGBV, in particular.
Relative Contribution of Diagnostic Testing to the Diagnosis of Respiratory Syncytial Virus in Hospitalized Adults in the United States
Authors: Anderson Evan J , Tippett Ashley , Begier Elizabeth , Gibson Theda , Ess Gabby , Patel Vikash , Taylor Meg , Reese Olivia , Salazar Luis , Jadhao Samadhan , Sun He-Ying , Hsiao Hui-Mien , Gupta Shadwal , Li Wensheng , Stephens Kathleen , Keane Amy , Ciric Caroline , Hellmeister Kieffer , Cheng Andrew , Al-Husein Zayna , Bristow Laurel , Hubler Robin , Liu Qing , Gessner Bradford D , Jodar Luis , Swerdlow David , Kalina Warren , Uppal Sonal , Kamidani Satoshi , Rouphael Nadine , Anderson Larry J , Rostad Christina A 
Published: July 2024

Abstract

Background
Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illness (ARI) in older adults. Optimizing diagnosis could improve understanding of RSV burden.

Methods
We enrolled adults ≥50 years of age hospitalized with ARI and adults of any age hospitalized with congestive heart failure or chronic obstructive pulmonary disease exacerbations at 2 hospitals during 2 respiratory seasons (2018–2020). We collected nasopharyngeal (NP) and oropharyngeal (OP) swabs (n = 1558), acute and convalescent sera (n = 568), and expectorated sputum (n = 153) from participants, and recorded standard-of-care (SOC) NP results (n = 805). We measured RSV antibodies by 2 immunoassays and performed BioFire testing on respiratory specimens.

Results
Of 1558 eligible participants, 92 (5.9%) tested positive for RSV by any diagnostic method. Combined NP/OP polymerase chain reaction (PCR) testing yielded 58 positives, while separate NP and OP testing identified 11 additional positives (18.9% increase). Compared to study NP/OP PCR alone, the addition of paired serology increased RSV detection by 42.9% (28 vs 40) among those with both specimen types, while the addition of SOC swab PCR increased RSV detection by 25.9% (47 vs 59).

Conclusions
The addition of paired serology testing, SOC swab results, and separate testing of NP and OP swabs improved RSV diagnostic yield in hospitalized adults.
Applications of Machine Learning on Electronic Health Record Data to Combat Antibiotic Resistance
Authors: Blechman Samuel E , Wright Erik S 
Published: July 2024

Abstract
There is growing excitement about the clinical use of artificial intelligence and machine learning (ML) technologies. Advancements in computing and the accessibility of ML frameworks enable researchers to easily train predictive models using electronic health record data. However, several practical factors must be considered when employing ML on electronic health record data. We provide a primer on ML and approaches commonly taken to address these challenges. To illustrate how these approaches have been applied to address antimicrobial resistance, we review the use of electronic health record data to construct ML models for predicting pathogen carriage or infection, optimizing empiric therapy, and aiding antimicrobial stewardship tasks. ML shows promise in promoting the appropriate use of antimicrobials, although clinical deployment is limited. We conclude by describing the potential dangers of, and barriers to, implementation of ML models in the clinic.
Innate and Cellular Immune Response to the Ebola Vaccine Ad26.ZEBOV, MVA-BN-Filo: An Ancillary Study of the EBL2001 Phase 2 Trial
Authors: Lacabaratz Christine , Durand Mélany , Wiedemann Aurélie , Foucat Emile , Surénaud Mathieu , Krief Corinne , Guillaumat Lydia , Robinson Cynthia , Luhn Kerstin , Bockstal Viki , Thiébaut Rodolphe , Richert Laura , Lévy Yves 
Published: July 2024

Abstract

Background
The EBL2001 phase 2 trial tested the 2-dose Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine in Europe. Safety and humoral immunogenicity assessments led to European Union market authorization in 2020. Complementary analyses of immune responses are warranted to better characterize vaccine effects.

Methods
We conducted an ancillary study to analyze changes in the serum and cellular responses. Serum biomarkers of activation/inflammation were evaluated using a Luminex assay. Vaccine-elicited T-cell responses and functions were evaluated by assessing their phenotype, cytokine production, proliferation, and cytotoxic potential. Integrated data analysis was performed through correlation and principal component analysis of serum biomarkers and cellular immune responses.

Results
Forty-eight volunteers were included. The Ad26.ZEBOV, MVA-BN-Filo vaccine elicited (1) serum increase of inflammatory/activation markers mainly at 1 day after the Ad26.ZEBOV vaccine; and (2) durable EBOV-specific T-cell proliferation and CD8+ T cells exhibiting a cytotoxic phenotype after Ad26.ZEBOV prime, after MVA-BN-Filo boost, and 6 months postvaccination. Integrated analysis revealed correlations between (1) EBOV-specific CD8+ T-cell proliferation and cytotoxic phenotype; and (2) high EBOV-specific CD8+ T-cell cytotoxic phenotype and low inflammatory marker IL-8 at day 1 postvaccination.

Discussion
This study provides unique insights into the in vivo contribution of proliferation/cytotoxic CD8+ T cells and inflammation to the Ad26.ZEBOV, MVA-BN-Filo vaccine-induced potency.
Clinical Trials Registration. NCT02416453.
Phylogenetic reconciliation: making the most of genomes to understand microbial ecology and evolution
Authors: Williams Tom A , Davin Adrian A , Szánthó Lénárd L , Stamatakis Alexandros , Wahl Noah A , Woodcroft Ben J , Soo Rochelle M , Eme Laura , Sheridan Paul O , Gubry-Rangin Cecile , Spang Anja , Hugenholtz Philip , Szöllősi Gergely J 
Published: July 2024

AbstractIn recent years, phylogenetic reconciliation has emerged as a promising approach for studying microbial ecology and evolution. The core idea is to model how gene trees evolve along a species tree and to explain differences between them via evolutionary events including gene duplications, transfers, and losses. Here, we describe how phylogenetic reconciliation provides a natural framework for studying genome evolution and highlight recent applications including ancestral gene content inference, the rooting of species trees, and the insights into metabolic evolution and ecological transitions they yield. Reconciliation analyses have elucidated the evolution of diverse microbial lineages, from Chlamydiae to Asgard archaea, shedding light on ecological adaptation, host–microbe interactions, and symbiotic relationships. However, there are many opportunities for broader application of the approach in microbiology. Continuing improvements to make reconciliation models more realistic and scalable, and integration of ecological metadata such as habitat, pH, temperature, and oxygen use offer enormous potential for understanding the rich tapestry of microbial life.
Calorie restriction in mice impairs cortical but not trabecular peak bone mass by suppressing bone remodeling
Authors: Liu Linyi , Le Phuong T , Stohn J Patrizia , Liu Hanghang , Ying Wangyang , Baron Roland , Rosen Clifford J 
Published: July 2024

Abstract
Calorie restriction (CR) can lead to weight loss and decreased substrate availability for bone cells. Ultimately, this can lead to impaired peak bone acquisition in children and adolescence and bone loss in adults. But the mechanisms that drive diet-induced bone loss in humans are not well characterized. To explore those in greater detail, we examined the impact of 30% CR for 4 and 8 wk in both male and female 8-wk-old C57BL/6 J mice. Body composition, areal bone mineral density (aBMD), skeletal microarchitecture by micro-CT, histomorphometric parameters, and in vitro trajectories of osteoblast and adipocyte differentiation were examined. After 8 wk, CR mice lost weight and exhibited lower femoral and whole-body aBMD vs ad libitum (AL) mice. By micro-CT, CR mice had lower cortical bone area fraction vs AL mice, but males had preserved trabecular bone parameters and females showed increased bone volume fraction compared to AL mice. Histomorphometric analysis revealed that CR mice had a profound suppression in trabecular as well as endocortical and periosteal bone formation in addition to reduced bone resorption compared to AL mice. Bone marrow adipose tissue was significantly increased in CR mice. In vitro, the pace of adipogenesis in bone marrow stem cells was greatly accelerated with higher markers of adipocyte differentiation and more oil red O staining, whereas osteogenic differentiation was reduced. qRT-PCR and western blotting suggested that the expression of Wnt16 and the canonical β-catenin pathway was compromised during CR. In sum, CR causes impaired peak cortical bone mass due to a profound suppression in bone remodeling. The increase in marrow adipocytes in vitro and in vivo is related to both progenitor recruitment and adipogenesis in the face of nutrient insufficiency. Long-term CR may lead to lower bone mass principally in the cortical envelope, possibly due to impaired Wnt signaling.
The contribution of academic inventors to regional technological diversification: the Italian evidence
Authors: Quatraro Francesco , Scandura Alessandra 
Published: July 2024

Abstract
This article investigates the interplay between scientific and technological capabilities in regional technological diversification dynamics by looking at the contributions of academic inventors. Combining the evolutionary economic approach and the theories on regional innovation capabilities on the one hand, and the distinctive features of academic inventors and university–industry patenting on the other, we hypothesize that the participation of university-based inventors to local patenting activity positively influences the chance of regional technological diversification and mitigates the path dependency engendered by the constraining role of the technological relatedness. In addition, we hypothesize that academic inventors tend to push regional technological trajectories towards their portfolio of specializations, hence allowing a process of technological convergence. The empirical results highlight the key role of academic institutions in the development of new regional technological trajectories while contributing to the academic and policy debate on regional diversification strategies.