bluuebunny/crossref_metadata_2025 huggingface dataset:
Tungsten-anisole complex provides 3,6-substituted cyclohexenes for highly diversified chemical libraries
Authors: Weatherford-Pratt Justin T. , Bloch Jeremy M. , Smith Jacob A. , Ericson Megan N. , Siela Daniel J. , Ortiz Mason R. , Shingler Mary H. , Fong Sarah , Laredo Jonathan A. , Patel Ishaan U. , McGraw Matt , Dickie Diane A. , Harman W. Dean
Published: February 2024

Medicinal chemists use vast combinatorial molecular libraries to develop leads for new pharmaceuticals. The syntheses of these compounds typically rely on coupling molecular fragments through atoms with planar (sp
2
) geometry. These so-called flat molecules often lack the protein binding site specificity needed to be an effective drug. Here, we demonstrate a coupling strategy in which a cyclohexene is used as a linker to connect two diverse molecular fragments while forming two new tetrahedral (sp
3
) stereocenters. These connections are made with the aid of a tungsten complex that activates anisole toward an unusual double protonation, followed by sequential nucleophilic additions. As a result, either cis- or trans-disubstituted cyclohexenes can be prepared with a range of chemical diversity unparalleled by other dearomatization methods.
STING licensing of type I dendritic cells potentiates antitumor immunity
Authors: Wang Jian , Li Suxin , Wang Maggie , Wang Xu , Chen Shuqing , Sun Zhichen , Ren Xiubao , Huang Gang , Sumer Baran D. , Yan Nan , Fu Yang-Xin , Gao Jinming
Published: February 2024

Stimulator of interferon genes (STING) is an immune adaptor protein that senses cyclic GMP-AMP in response to self or microbial cytosolic DNA as a danger signal. STING is ubiquitously expressed in diverse cell populations, including cancer cells, with distinct cellular functions, such as activation of type I interferons, autophagy induction, or triggering apoptosis. It is not well understood whether and which subsets of immune cells, stromal cells, or cancer cells are particularly important for STING-mediated antitumor immunity. Here, using a polymeric STING-activating nanoparticle (PolySTING) with a shock-and-lock dual activation mechanism, we show that conventional type 1 dendritic cells (cDC1s) are essential for STING-mediated rejection of multiple established and metastatic murine tumors. STING status in the host but not in the cancer cells (
Tmem173
−/−
) is important for antitumor efficacy. Specific depletion of cDC1 (
Batf3
−/−
) or STING deficiency in cDC1 (

XCR1
cre
STING
fl/fl

) abolished PolySTING efficacy, whereas depletion of other myeloid cells had little effect. Adoptive transfer of wild-type cDC1 in
Batf3
−/−
mice restored antitumor efficacy, whereas transfer of cDC1 with STING or IRF3 deficiency failed to rescue. PolySTING induced a specific chemokine signature in wild-type but not
Batf3
−/−
mice. Multiplexed immunohistochemistry analysis of STING-activating cDC1s in resected tumors correlates with patient survival. Furthermore, STING-cDC1 signature was increased after neoadjuvant pembrolizumab therapy in patients with non–small cell lung cancer. Therefore, we have defined that a subset of myeloid cells is essential for STING-mediated antitumor immunity with associated biomarkers for prognosis.
Staphylococcus aureus
AbcA transporter enhances persister formation under β-lactam exposure
Authors: Truong-Bolduc Q. C. , Wang Y. , Ferrer-Espada R. , Reedy J. L. , Martens A. T. , Goulev Y. , Paulsson J. , Vyas J. M. , Hooper D. C.
Published: February 2024

We evaluated the role of
Staphylococcus aureus
AbcA transporter in bacterial persistence and survival following exposure to the bactericidal agents nafcillin and oxacillin at both the population and single-cell levels. We show that AbcA overexpression resulted in resistance to nafcillin but not oxacillin. Using distinct fluorescent reporters of cell viability and AbcA expression, we found that over 6–14 hours of persistence formation, the proportion of AbcA reporter-expressing cells assessed by confocal microscopy increased sixfold as cell viability reporters decreased. Similarly, single-cell analysis in a high-throughput microfluidic system found a strong correspondence between antibiotic exposure and AbcA reporter expression. Persister cells grown in the absence of antibiotics showed neither an increase in nafcillin MIC nor in
abcA
transcript levels, indicating that survival was not associated with stable mutational resistance or
abcA
overexpression. Furthermore, persister cell levels on exposure to 1×MIC and 25×MIC of nafcillin decreased in an
abcA
knockout mutant. Survivors of nafcillin and oxacillin treatment overexpressed transporter AbcA, contributing to an enrichment of the number of persisters during treatment with pump-substrate nafcillin but not with pump-non-substrate oxacillin, indicating that efflux pump expression can contribute selectively to the survival of a persister population.
Diversity profiling of microbiomes associated with selected alpine plants and lichens from Mt. Suisho, Japan
Authors: Nakai Ryosuke , Munekawa Shouno , Murai Yoshinori , Ohmura Yoshihito , Tani Kenichiro
Published: February 2024

We report 16S rRNA gene amplicon data for the microbiomes in selected alpine plants (genera
Artemisia
,
Parnassia
, and
Phyllodoce
) and lichens (genera
Cladonia
and a mixture of
Miriquidica
and
Rhizocarpon
) from Mt. Suisho, Japan. Most of these samples were dominated by
Pseudomonadota
, while some contained the rarely cultivated phylum
Vulcanimicrobiota
(
Candidatus
Eremiobacterota/WPS-2).
Genome-scale metabolic modeling of the human milk oligosaccharide utilization by
Bifidobacterium longum
subsp.
infantis
Authors: Román Loreto , Melis-Arcos Felipe , Pröschle Tomás , Saa Pedro A. , Garrido Daniel
Published: February 2024

Bifidobacterium longum
subsp.
infantis
is a representative and dominant species in the infant gut and is considered a beneficial microbe. This organism displays multiple adaptations to thrive in the infant gut, regarded as a model for human milk oligosaccharides (HMOs) utilization. These carbohydrates are abundant in breast milk and include different molecules based on lactose. They contain fucose, sialic acid, and N-acetylglucosamine.
Bifidobacterium
metabolism is complex, and a systems view of relevant metabolic pathways and exchange metabolites during HMO consumption is missing. To address this limitation, a refined genome-scale network reconstruction of this bacterium is presented using a previous reconstruction of
B. infantis
ATCC 15967 as a template. The latter was expanded based on an extensive revision of genome annotations, current literature, and transcriptomic data integration. The metabolic reconstruction (
i
LR578) accounted for 578 genes, 1,047 reactions, and 924 metabolites. Starting from this reconstruction, we built context-specific genome-scale metabolic models using RNA-seq data from cultures growing in lactose and three HMOs. The models revealed notable differences in HMO metabolism depending on the functional characteristics of the substrates. Particularly, fucosyl-lactose showed a divergent metabolism due to a fucose moiety. High yields of lactate and acetate were predicted under growth rate maximization in all conditions, whereas formate, ethanol, and 1,2-propanediol were substantially lower. Similar results were also obtained under near-optimal growth on each substrate when varying the empirically observed acetate-to-lactate production ratio. Model predictions displayed reasonable agreement between central carbon metabolism fluxes and expression data across all conditions. Flux coupling analysis revealed additional connections between succinate exchange and arginine and sulfate metabolism and a strong coupling between central carbon reactions and adenine metabolism. More importantly, specific networks of coupled reactions under each carbon source were derived and analyzed. Overall, the presented network reconstruction constitutes a valuable platform for probing the metabolism of this prominent infant gut bifidobacteria.

IMPORTANCE

This work presents a detailed reconstruction of the metabolism of
Bifidobacterium longum
subsp.
infantis
, a prominent member of the infant gut microbiome, providing a systems view of its metabolism of human milk oligosaccharides.
Development of a rapid detection method for the macrolide resistance gene in
Mycobacterium avium
using the amplification refractory mutation system–loop-mediated isothermal amplification method
Authors: Inagaki Takayuki , Asahi Shoki , Ogawa Kenji , Nakagawa Taku , Ohkura Teruko , Osada Yukari , Nikai Toshiaki , Yamada Kiyofumi , Yagi Tetsuya , Uchiya Kei-ichi
Published: February 2024

Macrolide antibiotics such as clarithromycin (CLR) and azithromycin are the key drugs used in multidrug therapy for
Mycobacterium avium
complex (MAC) diseases. For these antibacterial drugs, drug susceptibility has been correlated with clinical response in MAC diseases. We have previously demonstrated the correlation between drug susceptibility and mutations in the 23S rRNA gene, which confers resistance to macrolides. Herein, we developed a rapid detection method using the amplification refractory mutation system (ARMS)–loop-mediated isothermal amplification (LAMP) technique to identify mutations in the 23S rRNA gene of
M. avium
. We examined the applicability of the ARMS–LAMP method to genomic DNA extracted from six genotypes of
M. avium
clinical isolates. The
M. avium
isolates were classified into 21 CLR-resistant and 9 CLR-susceptible strains based on the results of drug susceptibility tests; the 23S rRNA genes of these strains were sequenced and analyzed using the ARMS–LAMP method. Sequence analysis revealed that the 9 CLR-sensitive strains were wild-type strains, whereas the 21 CLR-resistant strains comprised 20 mutant-type strains and one wild-type strain. Using ARMS–LAMP, no amplification from genomic DNAs of the 10 wild-type strains was observed using the mutant-type mismatch primer sets (MTPSs); however, amplification from the 20 mutant-type strain DNAs was observed using the MTPSs. The rapid detection method developed by us integrates ARMS–LAMP with a real-time turbidimeter, which can help determine drug resistance in a few hours. In conclusion, ARMS–LAMP might be a new clinically beneficial technology for rapid detection of mutations.

IMPORTANCE

Multidrug therapy for pulmonary
Mycobacterium avium
complex disease is centered on the macrolide antibiotics clarithromycin and azithromycin, and resistance to macrolides is an important prognosticator for clinical aggravation. Therefore, it is important to develop a quick and easy method for detecting resistance to macrolides. Drug resistance is known to be correlated with mutations in macrolide resistance genes. We developed a rapid detection method using amplification refractory mutation system (ARMS)–loop-mediated isothermal amplification (LAMP) to identify a mutation in the 23S rRNA gene, which is a macrolide resistance gene. Furthermore, we examined the applicability of this method using
M. avium
clinical isolates. The rapid method developed by us for detection of the macrolide resistance gene by integrating ARMS–LAMP and a real-time turbidimeter can help in detection of drug resistance within a few hours. Since this method does not require expensive equipment or special techniques and shows high analytical speed, it would be very useful in clinical practice.
SARS-CoV-2 infection in brown-headed spider monkeys (
Ateles fusciceps
) at a wildlife rescue center on the coast of Ecuador—South America
Authors: Carvajal Mateo , Saenz Carolina , Fuentes Nathalia , Guevara Rommel , Muñoz Erika , Prado-Vivar Belen , Diaz Eduardo , Alfonso-Cortes Felipe , Coloma Josefina , Grunauer Michelle , Rojas-Silva Patricio , Cardenas Paul A. , Barragan Veronica
Published: February 2024

Human populations can be affected in unpredictable ways by the emergence and spread of zoonotic diseases. The COVID-19 (coronavirus disease of 2019) pandemic was a reminder of how devastating these events can be if left unchecked. However, once they have spread globally, the impact of these diseases when entering non-exposed wildlife populations is unknown. The current study reports the infection of brown-headed spider monkeys (
Ateles fusciceps
) at a wildlife rescue center in Ecuador. Four monkeys were hospitalized, and all tested positive for SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) by RT-qPCR (Quantitative Reverse Transcription PCR). Fecal samples (
n
= 12) from monkeys at the rescue center also tested positive; three zookeepers responsible for feeding and deworming the monkeys also tested positive, suggesting human-animal transmission. Whole genome sequencing identified most samples’ omicron clade 22B BA.5 lineage. These findings highlight the threat posed by an emerging zoonotic disease in wildlife species and the importance of preventing spillover and spillback events during epidemic or pandemic events.

IMPORTANCE

Although COVID-19 (coronavirus disease of 2019) has been primarily contained in humans through widespread vaccination, the impact and incidence of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus) and its transmission and epidemiology in wildlife may need to be addressed. In some natural environments, the proximity of animals to humans is difficult to control, creating perfect scenarios where susceptible wildlife can acquire the virus from humans. In these places, it is essential to understand how transmission can occur and to develop protocols to prevent infection. This study reports the infection of brown-headed spider monkeys with SARS-CoV-2, a red-listed monkey species, at a wildlife recovery center in Ecuador. This study reports the infection of brown-headed spider monkeys with SARS-CoV-2, indicating the potential for transmission between humans and wildlife primates and the importance of preventing such events in the future.
Paleozoic evolution of the Yukon-Tanana terrane of the North American Cordillera, NW British Columbia
Authors: Soucy La Roche R. , Zagorevski A. , Joyce N.L. , Crowley J.L.
Published: February 2024

The origins and primary relationships between tectono-stratigraphic units are fundamental to the terrane concept in accretionary orogens, but they are challenging to assess in metamorphic terranes. In NW British Columbia, three tectonically bounded metamorphic suites of the Yukon-Tanana terrane formed in distinct tectonic settings, based on high-spatial-resolution geochronology and immobile trace-element geochemistry. The Florence Range suite comprises late Neoproterozoic or younger to pre–latest Devonian metasedimentary rocks derived from continental crust, 360 ± 4 Ma calc-alkaline intermediate orthogneiss, and 357 ± 4 Ma amphibolite with oceanic-island basalt composition, consistent with rifting of a continental margin. The detrital signature is dominated by late Mesoproterozoic zircon, which indicates different sources than other parts of the Yukon-Tanana terrane. The Boundary Ranges suite comprises pre–Late Devonian metasedimentary rocks derived in part from a mafic source, amphibolite derived from subduction-zone metasomatized mantle, and 369 ± 4 Ma to 367 ± 7 Ma calc-alkaline felsic to intermediate orthogneiss. The Whitewater suite comprises meta-chert, graphite-rich metapelite, and amphibolite with back-arc basin basalt composition consistent with an anoxic basin near a volcanic source. Our data indicate that the Florence Range and Boundary Ranges suites were separate until at least the Early Mississippian and may have formed a composite terrane since the Permian, whereas the relationship with the Whitewater suite is uncertain. We compare the Paleozoic evolution of the Yukon-Tanana terrane in NW British Columbia with several modern analogues in the west and southwest Pacific Ocean.
Extended CPAP or low-flow nasal cannula for intermittent hypoxaemia in preterm infants: a 24-hour randomised clinical trial
Authors: Yazdi Siamak , Carlo Waldemar A , Nakhmani Arie , Boateng Ernestina O , Aban Immaculada , Ambalavanan Namasivayam , Travers Colm P
Published: February 2024

Objective

Optimal timing of continuous positive airway pressure (CPAP) cessation in preterm infants remains undetermined. We hypothesised that CPAP extension compared with weaning to low-flow nasal cannula (NC) reduces intermittent hypoxaemia (IH) and respiratory instability in preterm infants meeting criteria to discontinue CPAP.

Design

Single-centre randomised clinical trial.

Setting

Level 4 neonatal intensive care unit.

Patients

36 infants <34 weeks’ gestation receiving CPAP≤5 cmH2O and fraction of inspired oxygen (FiO2) ≤0.30 and meeting respiratory stability criteria.

Interventions

Extended CPAP was compared with weaning to low-flow NC (0.5 L/kg/min with a limit of 1.0 L/min) for 24 hours.

Outcomes

The primary outcome was IH (number of episodes with SpO2<85% lasting ≥10 s). Secondary outcomes included: coefficient of variability of SpO2, proportion of time in various SpO2ranges, episodes (≥10 s) with SpO2<80%, median cerebral and renal oxygenation, median effective FiO2, median transcutaneous carbon dioxide and bradycardia (<100/min for≥10 s).

Results

The median (IQR) episodes of IH per 24-hour period was 20 (6–48) in the CPAP group and 76 (18–101) in the NC group (p=0.03). Infants continued on CPAP had less bradycardia, time with SpO2<91% and <85%, and lower FiO2(all p<0.05). There were no statistically significant differences in IH<80%, median transcutaneous carbon dioxide or median cerebral or renal oxygenation.

Conclusion

In preterm infants meeting respiratory stability criteria for CPAP cessation, extended CPAP decreased IH, bradycardia and other hypoxaemia measures compared with weaning to low-flow NC during the 24-hour intervention.

Trial registration number

NCT04792099.
Why a good law is not always good enough: a global review of restrictions to supportive laws for sexual and reproductive health and rights
Authors: Ferguson Laura , Anderson Michelle Elizabeth , Liang Mengjia , Filmer-Wilson Emilie
Published: February 2024

Laws and regulations provide the framework for implementing sexual and reproductive health and rights (SRHR)-related policies, programmes and services. They can promote the fulfilment of health and human rights; however, they may also limit the achievement of these goals. This study uses data collected under Sustainable Development Goal Indicator 5.6.2 to analyse SRHR-related laws and restrictions from 153 countries. Looking beyond the existence of supportive laws to assess the constellation of legal restrictions and contradictions such as criminalisation and plural legal systems provides a more nuanced understanding of factors involved in achieving full and equal access to SRHR.

The interaction between restrictions and contradictions within the law disproportionately impacts some populations’ health access and outcomes. Restrictions based on third-party authorisations and age are the most common restriction types, disproportionately impacting young women. Contraception, emergency contraception and abortion face the greatest number of restrictions, indicating a significant layering of barriers to family planning services. Further, plural legal systems commonly contradict guarantees of contraceptive services and emergency contraception. Our analyses suggest that one of the populations most affected by restrictions to SRH services as they appear in legal and regulatory frameworks is adolescent girls and young women in sub-Saharan Africa seeking abortion or contraceptive services.

Study findings provide a critical starting point for advocacy to address legal barriers to SRH services and evidence for future policy and programming. For individual countries, this study can serve as a model for analysis of their own legal and regulatory frameworks to identify priority areas for reform efforts.
Preoperative surgeon evaluation of corneal endothelial status: the Viability Control of Human Endothelial Cells before Keratoplasty (V-CHECK) study protocol
Authors: Airaldi Matteo , Zheng Yalin , Aiello Francesco , Bachmann Björn , Baydoun Lamis , Ní Dhubhghaill Sorcha , Dickman Mor M , Kaye Stephen B , Fontana Luigi , Gadhvi Kunal A , Moramarco Antonello , Rodriguez Calvo de Mora Marina , Rocha de Lossada Carlos , Scorcia Vincenzo , Viola Pietro , Calza Stefano , Levis Hannah J , Parekh Mohit , Ruzza Alessandro , Ferrari Stefano , Ponzin Diego , Semeraro Francesco , Romano Vito
Published: February 2024

Introduction

The success of keratoplasty strongly depends on the health status of the transplanted endothelial cells. Donor corneal tissues are routinely screened for endothelial damage before shipment; however, surgical teams have currently no means of assessing the overall viability of corneal endothelium immediately prior to transplantation. The aim of this study is to validate a preoperative method of evaluating the endothelial health of donor corneal tissues, to assess the proportion of tissues deemed suitable for transplantation by the surgeons and to prospectively record the clinical outcomes of a cohort of patients undergoing keratoplasty in relation to preoperatively defined endothelial viability.

Methods and analysis

In this multicentre cohort study, consecutive patients undergoing keratoplasty (perforating keratoplasty, Descemet stripping automated endothelial keratoplasty (DSAEK), ultra-thin DSAEK (UT-DSAEK) or Descemet membrane endothelial keratoplasty) will be enrolled and followed-up for 1 year. Before transplantation, the endothelial viability of the donor corneal tissue will be evaluated preoperatively through trypan blue staining and custom image analysis to estimate the overall percentage of trypan blue-positive areas (TBPAs), a proxy of endothelial damage. Functional and structural outcomes at the end of the follow-up will be correlated with preoperatively assessed TBPA values.

Ethics and dissemination

The protocol will be reviewed by the ethical committees of participating centres, with the sponsor centre issuing the final definitive approval. The results will be disseminated on ClinicalTrials.gov, at national and international conferences, by partner patient groups and in open access, peer-reviewed journals.

Trial registration number

NCT05847387.
Initiating medical abortion in an emergency department in the United States
Authors: Preiksaitis Carl , Saxena Monica , Henkel Andrea
Published: February 2024

Objectives

The primary objective of this study was to assess the feasibility of initiating medical abortions in a large, academic emergency department (ED) in the United States.

Methods

A retrospective case series analysis was conducted to evaluate a protocol for initiating medical abortion in the ED implemented from January 2020 to October 2023 at an academic, tertiary care hospital in California, USA. Participants included ED patients diagnosed with pregnancies in the first trimester that were undesired and who opted for medical abortion. The medical abortion protocol was collaboratively designed by a multidisciplinary team and follow-up was conducted by our institution’s gynaecology department. Data were sourced from a data repository of electronic health records and subjected to descriptive statistical analysis.

Results

A total of 27 eligible patients initiated medical abortions in the ED during the study period. The cohort was diverse in terms of racial and ethnic backgrounds and almost evenly split between private and public insurance. No patients had significant complications identified in the medical record. Two patients required uterine aspiration by the gynaecology team; one patient in clinic and one during a return visit to the ED.

Conclusions

Data from this case series suggest that initiating medical abortion in the ED is feasible. The ED may be considered as an additional access point for abortion care services, especially in areas where other care options are not readily available. Educational, legal and regulatory frameworks that allow emergency physicians to take a greater role in providing this care should be considered.
State expansion of Supplemental Nutrition Assistance Program eligibility and rates of firearm-involved deaths in the United States
Authors: Sokol Rebeccah Lyn , Austin Anna E
Published: February 2024

Introduction

Poverty is a consistent correlate of firearm-involved mortality, yet little work has considered the effects of social and economic policies on these deaths. This study examined associations of state elimination of the asset test and increases in the income limit for Supplemental Nutrition Assistance Program (SNAP) eligibility with rates of firearm-involved suicide and homicide deaths in the United States.

Methods

This ecological repeated cross-sectional study used 2015–2019 data from the SNAP Policy Database and death certificate data from the National Vital Statistics System. The exposures were (1) state elimination of the asset test for SNAP eligibility and (2) state elimination of the asset test and increases in the income limit for SNAP eligibility, compared with (3) state adoption of neither policy. The outcomes were firearm-involved suicide deaths and firearm-involved homicide deaths. The research team conducted mixed-effects regressions to estimate associations.

Results

State elimination of the asset test for SNAP eligibility (incidence rate ratio (IRR), 0.67; 95% CI, 0.48 to 0.91) and state adoption of both eliminating the asset test and increasing the income limit for SNAP eligibility (IRR, 0.68; 95% CI, 0.49 to 0.92) were associated with decreased rates of firearm-involved suicide deaths compared with state adoption of neither policy. There were no associations with state firearm-involved homicide rates.

Conclusions

SNAP is an important social safety net programme that addresses food insecurity, and the present results suggest it may also contribute to reducing firearm-involved suicide.
Assessing embodied carbon for reinforced concrete structures in Canada
Authors: Sheng Kathy , Woods Joshua E. , Bentz Evan , Hoult Neil A.
Published: February 2024

The global emphasis on reducing greenhouse gas emissions means that engineers and architects are increasingly required to account for embodied carbon in their designs. However, there is a lack of knowledge and tools in the structural engineering community to enable calculation of embodied carbon for reinforced concrete structures. This paper aims to address this concern by providing a review of the most up-to-date approaches for calculating embodied carbon as well as the important factors that engineers should consider during the design phase to reduce embodied carbon. Environmental product declarations for concrete in four Canadian provinces will also be compared to illustrate the variability in the embodied carbon and the factors that influence this variability. Finally, the paper will present a case-study on the design of a reinforced concrete beam to demonstrate how to calculate embodied carbon and to illustrate how changes in design can influence the total embodied carbon.
Wood traits of Tectona grandis during the 2015–2016 El Niño drought in the Amazon
Authors: do Carmo Fábio Henrique Della Justina , Volpato Maristela , Santos Ataíde Glaycianne Christine Vieira dos , Paz Castro Jonnys , Takizawa Fausto Hissashi , Latorraca João Vicente de Figueiredo
Published: February 2024

The Amazon biome is influenced by El Niño event, which reduce precipitation and increase temperature. However, little is known about its effects on tree formation dynamics in this region. Here, we evaluated the effects of local (precipitation, temperature, and solar insolation) and large-scale (El Niño) climatic variables on wood traits of Tectona grandis (teak) in the Amazon. Discs were collected from the base of trees aged 12 years and used for anatomical and physical analyses. We evaluated three periods (i.e., pre-El Niño (2012/2013), El Niño (2014/2015), and post-El Niño (2016/2017)). Wood density, vessels, and rays were compared to local and large-scale climatic variables. The extreme drought caused by El Niño event reduced the width and length of teak vessels. Additionally, precipitation during some months of the year increased vessel size and wood density. In some months of the year, ambient temperature reduced vessel width and length. Moreover, the effect of solar insolation depended on soil moisture availability. Thus, our results provided clear evidence of teak acclimatization to El Niño in the Amazon region and should promote further studies on tree responses to climate.
Evaluation of branch sampling, ocular assessments, and aerial surveys for estimating spruce budworm defoliation
Authors: Donovan Shawn , MacLean David A.
Published: February 2024

We compared three methods for estimating current-year spruce budworm ( Choristoneura fumiferana (Clem.)) defoliation from 2014 to 2021 using a network of 99 permanent sample plots in central Gaspé Peninsula, Québec. Percent current-year defoliation was measured by assessing shoots from mid-crown branches, ocular ratings of all individual trees using binoculars, and provincial government aerial surveys. Ocular survey defoliation differed from branch sample defoliation in 5–6 out of 7 years, consistently underestimating defoliation, across the full range of defoliation severity observed. Nested mixed-effect models for fir–spruce combined, balsam fir, white spruce, and black spruce ocular survey defoliation bias resulted in marginal R2 of 0.40, 0.47, 0.82, and 0.86, respectively. Current defoliation severity and its interaction with previous year defoliation and weather conditions significantly affected ocular survey bias. Correspondence of aerial survey estimates and mean plot defoliation occurred in only 43% of all plot-years and ranged from 14%–58% in individual years. Differences between aerial survey defoliation and plot values mainly resulted from assigning an adjacent class (e.g., light <30% assigned as moderate 31%–70% defoliation) or misplaced defoliation polygon boundaries, suggesting that assignment of aerial survey defoliation to plots or specific ground areas needs ground truth sampling.
Dissolved black carbon in aquatic environments with an emphasis on lacustrine systems: a review
Authors: Saeed Sumbul , Riaz Rahat , Zhang Gan , Li Jun , Naseem Malik Riffat
Published: February 2024

Dissolved black carbon (DBC) is the remobilized soluble fraction of black carbon (BC). DBC, present in all aquatic environments, is a heterogeneous mixture of various pyrogenic aromatics. For a long time, oceans were solely considered to be the largest pool of DBC. However, recent research indicates that lakes might also contain significant concentrations of DBC. Anthropogenic BC emissions and seasonal changes driven by climate change could increase DBC flux to glacial and fluvial lacustrine systems with unique effects. In this article, current knowledge concerning the formation, sources, transportation, fate, and environmental implications of DBC in lacustrine networks is presented. Furthermore, ambiguities pertaining to terminology and methodologies used in the separation and quantification of DBC are also reviewed, and research gaps that should be addressed in future studies are highlighted. Constraining DBC dynamics and residence times in lacustrine systems could provide valuable insights into anthropogenic perturbations of the global carbon cycle.
Children's Acceptance of a Domestic Social Robot: How It Evolves over Time
Authors: De Jong Chiara , Peter Jochen , Kühne Rinaldo , Barco Alex
Published: February 2024

Little is known about children's long-term acceptance of social robots; whether different types of users exist; and what reasons children have not to use a robot. Moreover, the literature is inconclusive about how the measurement of children's robot acceptance (i.e., self-report or observational) affects the findings. We relied on both self-report and observational data from a six-wave panel study among 321 children aged eight to nine, who were given a Cozmo robot to play with at home over the course of 8 weeks. Children's robot acceptance decreased over time, with the strongest drop after 2–4 weeks. Children rarely rejected the robot (i.e., they did not stop using it already prior to actual adoption). They rather discontinued its use after initial adoption or alternated between using and not using the robot. The competition of other toys and lacking motivation to play with Cozmo emerged as the strongest reasons for not using the robot. Self-report measures captured patterns of robot acceptance well but seemed suboptimal for precise assessments of robot use.
Enhancing Online Accessibility of Digitized Artifacts from Small Museum Collections in Cyprus: An Empirical Evaluation of the CyprusArk Solution
Authors: Avgousti A. , Papaioannou G. , Hermon S.
Published: February 2024

Small museums play a pivotal role in the Cyprus cultural landscape by carefully safeguarding and curating historical artifacts, thereby showcasing the country's rich heritage. However, in order to enhance accessibility to a wider audience, it is crucial to make these objects available online. This research aims to explore the effectiveness of the CyprusArk solution (a high-fidelity prototype) in enhancing the online presence of digitized artifacts within Cypriot small museums. By collecting and analyzing qualitative data from six out of ten classified as small museums, the study aims to demonstrate the potential of such solutions, specifically designed for small museums in Cyprus. CyprusArk is a Content Management System, serving as a stand-alone platform for each museum. Instances of the solution will be hosted, supported, and maintained at a Cyprus national infrastructure in a high-performance computer facility (HPC), at The Cyprus Institute (CyI). The study has broader implications for the global museum sector, as it showcases the potential of new digital tools to enhance online access to cultural heritage resources and contribute to the dissemination of information “knowledge” among the broader population.
Identification and Genomic Analyses of a Multidrug Resistant Avian Pathogenic Escherichia coli Coharboring mcr-1, blaTEM-176 and blaCTX-M-14 Genes
Authors: Wang Zhiyang , Wang Xinyu , Guo Weiqi , Wang Di , Hu Jiangang , Zhang Beibei , Qi Jingjing , Tian Mingxing , Bao Yanqing , Li Haihua , Wang Shaohui
Published: February 2024

The emergence and transmission of the colistin‐resistance gene mcr and extended‐spectrum β‐lactamase (ESBL) encoding genes pose a significant threat to global public health. In recent years, it has been reported that mcr-1 and ESBL genes can coexist in single bacteria strain. The objective of this study was to characterize a multidrug‐resistant (MDR) avian pathogenic Escherichia coli (APEC) isolate carrying mcr and ESBL encoding genes in China. A total of 200 APEC isolates were collected for antimicrobial susceptibility testing by Kirby–Bauer (K–B) disk method. The MDR strain EC012 were then further analyzed for minimum inhibitory concentrations, antimicrobials resistance genes (ARGs) detection, conjugation, and whole‐genome sequencing (WGS). Among all APEC isolates determined by K–B disk method, strain EC012 was resistant to almost all the antimicrobials, including polymyxin B, cefotaxime, and ceftazidime. Moreover, EC012 harbored ARGs mcr-1, blaTEM-176, and blaCTX-M-14. WGS analysis revealed that EC012 belonged to epidemic APEC serotype O1:H16 and multilocus sequence type ST295. EC012 consisted of one chromosome and six plasmids, encoding a broad ARGs. The blaCTX-M-14, mcr-1 or blaTEM-176 genes were located on conjugative plasmids pEC012‐1 or pEC012‐5, respectively. These plasmids were successfully transferred to transconjugants and resulted in the resistance to polymyxin B, cefotaxime, and ceftazidime. This study indicated that APEC was a potential reservoir of colistin‐resistance gene mcr-1 and ESBL encoding genes, and highlighted the necessity for enhanced monitoring of ARGs dissemination among bacteria from different origins.
The Flow Rate of the Condenser Cooling Water in the Distillation Process Increases the Quality and Quantity of Patchouli Oil
Authors: Smith Husein , Assagaf Muhammad , Suwarda Rosniyati , Budiyanto Agus , Adinegoro Himawan , Manalu Lamhot Parulian , Rienoviar  , Rosniati  , Manoi Feri , Loppies Justus Elisa , Ramlah Sitti , Sunarmani  , Widayanti Siti Mariana , Setyadjit  , Marwati Tri , Setyawan Nurdi , Tjahjohutomo Rudy , Syaefullah Enrico , Risfaheri  , Arif Abdullah Bin
Published: February 2024

Indonesia is an important essential oil-exporting country globally, where 40 types of essential oils have been traded on the international market and are products of Indonesia. However, the quality and quantity of patchouli oil produced in Indonesia are still low. Most essential oil processing units use simple or traditional technology and generally have limited production capacity. This study aimed to obtain the optimum water flow rate in a condenser system for patchouli oil production in Maluku, Indonesia. Patchouli oil extraction from fresh patchouli leaves and twigs was carried out by increasing the condenser water discharge rate. Patchouli oil extraction with a condenser cooling water discharge treatment of 1.74 L/min and drying time for 5 days produced the highest patchouli oil yield of 1.4%. The greater the condenser water discharge rate, the better the yield and accumulation of patchouli oil recovery obtained. In addition, based on the results of the analysis of the composition of patchouli oil compounds with GCMS, it can be seen that 13 compounds can be detected in patchouli oil. The three main components of patchouli oil in all condenser cooling water treatments were alpha-guaiene, delta-guaiene, and patchouli alcohol. Considering the results of all parameters mentioned above, the treatment of the condenser cooling water discharge of 1.74 L/min and drying time for 5 days increases the quality and quantity of patchouli oil.
Supplementary Figure S1 from Clinical Benefit of Avapritinib in KIT-Mutant Gastrointestinal Stromal Tumors: A Post Hoc Analysis of the Phase I NAVIGATOR and Phase I/II CS3007–001 Studies
Authors: Heinrich Michael C. , Zhang Xinhua , Jones Robin L. , George Suzanne , Serrano César , Deng Yanhong , Bauer Sebastian , Cai Shirong , Wu Xin , Zhou Yongjian , Tao Kaixiong , Zheng Zhichao , Zhang Jun , Cui Yuehong , Cao Hui , Wang Meining , Hu Jin , Yang Jason , Li Jian , Shen Lin
Published: February 2024

Supplementary Figure S1. Examples of remarkable tumor regression in patients with KIT-only-mutant GIST during treatment with avapritinib 300 mg QD.
Supplementary Methods 1 from PD-1 Expression on Intratumoral Regulatory T Cells Is Associated with Lack of Benefit from Anti–PD-1 Therapy in Metastatic Clear-Cell Renal Cell Carcinoma Patients
Authors: Denize Thomas , Jegede Opeyemi A. , Matar Sayed , El Ahmar Nourhan , West Destiny J. , Walton Emily , Bagheri Aseman Sheshdeh , Savla Varunika , Nabil Laimon Yasmin , Gupta Saurabh , Vemula Sai Vikram , Braun David A. , Burke Kelly P. , Catalano Paul J. , Freeman Gordon J. , Motzer Robert J. , Atkins Michael B. , McDermott David F. , Sharpe Arlene H. , Choueiri Toni K. , Signoretti Sabina
Published: February 2024

Supplementary Methods
Supplementary Table S5 from Phase Ia/b Study of Giredestrant ± Palbociclib and ± Luteinizing Hormone-Releasing Hormone Agonists in Estrogen Receptor–Positive, HER2-Negative, Locally Advanced/Metastatic Breast Cancer
Authors: Jhaveri Komal L. , Bellet Meritxell , Turner Nicholas C. , Loi Sherene , Bardia Aditya , Boni Valentina , Sohn Joohyuk , Neilan Tomas G. , Villanueva-Vázquez Rafael , Kabos Peter , García-Estévez Laura , López-Miranda Elena , Pérez-Fidalgo J. Alejandro , Pérez-García Jose M. , Yu Jiajie , Fredrickson Jill , Moore Heather M. , Chang Ching-Wei , Bond John W. , Eng-Wong Jennifer , Gates Mary R. , Lim Elgene
Published: February 2024

Table S5. Giredestrant and palbociclib steady-state pharmacokinetic parameters.
Supplementary Table S4 from Phase Ia/b Study of Giredestrant ± Palbociclib and ± Luteinizing Hormone-Releasing Hormone Agonists in Estrogen Receptor–Positive, HER2-Negative, Locally Advanced/Metastatic Breast Cancer
Authors: Jhaveri Komal L. , Bellet Meritxell , Turner Nicholas C. , Loi Sherene , Bardia Aditya , Boni Valentina , Sohn Joohyuk , Neilan Tomas G. , Villanueva-Vázquez Rafael , Kabos Peter , García-Estévez Laura , López-Miranda Elena , Pérez-Fidalgo J. Alejandro , Pérez-García Jose M. , Yu Jiajie , Fredrickson Jill , Moore Heather M. , Chang Ching-Wei , Bond John W. , Eng-Wong Jennifer , Gates Mary R. , Lim Elgene
Published: February 2024

Table S4. Clinical benefit rate in selected subgroups of patients.
Supplementary Table S2 from Phase Ia/b Study of Giredestrant ± Palbociclib and ± Luteinizing Hormone-Releasing Hormone Agonists in Estrogen Receptor–Positive, HER2-Negative, Locally Advanced/Metastatic Breast Cancer
Authors: Jhaveri Komal L. , Bellet Meritxell , Turner Nicholas C. , Loi Sherene , Bardia Aditya , Boni Valentina , Sohn Joohyuk , Neilan Tomas G. , Villanueva-Vázquez Rafael , Kabos Peter , García-Estévez Laura , López-Miranda Elena , Pérez-Fidalgo J. Alejandro , Pérez-García Jose M. , Yu Jiajie , Fredrickson Jill , Moore Heather M. , Chang Ching-Wei , Bond John W. , Eng-Wong Jennifer , Gates Mary R. , Lim Elgene
Published: February 2024

Table S2. Overview of adverse events in the safety-evaluable population.
Supplementary Figure S3 from Phase Ia/b Study of Giredestrant ± Palbociclib and ± Luteinizing Hormone-Releasing Hormone Agonists in Estrogen Receptor–Positive, HER2-Negative, Locally Advanced/Metastatic Breast Cancer
Authors: Jhaveri Komal L. , Bellet Meritxell , Turner Nicholas C. , Loi Sherene , Bardia Aditya , Boni Valentina , Sohn Joohyuk , Neilan Tomas G. , Villanueva-Vázquez Rafael , Kabos Peter , García-Estévez Laura , López-Miranda Elena , Pérez-Fidalgo J. Alejandro , Pérez-García Jose M. , Yu Jiajie , Fredrickson Jill , Moore Heather M. , Chang Ching-Wei , Bond John W. , Eng-Wong Jennifer , Gates Mary R. , Lim Elgene
Published: February 2024

Figure S3.
Early changes from baseline in ESR1 ctDNA VAFs. Absolute ESR1 VAF by giredestrant dose (A) or by clinical benefit (B) at baseline, C1D15 and C2D1. (A–B) Individual lines represent matched ESR1 ctDNA results from a single patient across time points. (C) Boxplots of absolute
ESR1 VAF grouped by treatment and clinical benefit. (A–C) ESR1 VAF is represented as the sum of all detected ESR1 VAFs at each time point. The giredestrant 100 mg +palbociclib ±LHRH cohort includes three patients from the cardiac evaluation cohort who initiated single-agent
giredestrant 100 mg on cycle 1, day –14, and then continued on giredestrant 100 mg +palbociclib on cycle 1, day 1. Relative change of ESR1 VAF from baseline by giredestrant dose (D) or by clinical benefit (E). (D–E) Only patients with detectable ESR1 VAF at baseline are included. Bars represent mean relative change with standard deviation; dots represent individual relative changes. (C–E) For patients with results from more than one ctDNA baseline sample, the sum ESR1 VAF from the sample collected closest to C1D1 was used for calculating relative change.
Supplementary Figure S2 from Phase Ia/b Study of Giredestrant ± Palbociclib and ± Luteinizing Hormone-Releasing Hormone Agonists in Estrogen Receptor–Positive, HER2-Negative, Locally Advanced/Metastatic Breast Cancer
Authors: Jhaveri Komal L. , Bellet Meritxell , Turner Nicholas C. , Loi Sherene , Bardia Aditya , Boni Valentina , Sohn Joohyuk , Neilan Tomas G. , Villanueva-Vázquez Rafael , Kabos Peter , García-Estévez Laura , López-Miranda Elena , Pérez-Fidalgo J. Alejandro , Pérez-García Jose M. , Yu Jiajie , Fredrickson Jill , Moore Heather M. , Chang Ching-Wei , Bond John W. , Eng-Wong Jennifer , Gates Mary R. , Lim Elgene
Published: February 2024

Figure S2.
Reduction in FES uptake as measured by mean percent change from baseline in background-corrected maximum standardized uptake value indicates target engagement and robust reduction in ER activity across all doses. The asterisks indicate patients with
baseline ESR1 mutations. (A) FES-PET scans demonstrating FES-avid disease at baseline and reduced FES uptake on treatment in patients treated with 90 mg (left) and 250 mg
giredestrant (right) (B).
Supplementary Table S3 from Phase I/II Study of the WEE1 Inhibitor Adavosertib (AZD1775) in Combination with Carboplatin in Children with Advanced Malignancies: Arm C of the AcSé-ESMART Trial
Authors: Gatz Susanne A. , Harttrampf Anne C. , Brard Caroline , Bautista Francisco , André Nicolas , Abbou Samuel , Rubino Jonathan , Rondof Windy , Deloger Marc , Rübsam Marc , Marshall Lynley V. , Hübschmann Daniel , Nebchi Souad , Aerts Isabelle , Thebaud Estelle , De Carli Emilie , Defachelles Anne Sophie , Paoletti Xavier , Godin Robert , Miah Kowser , Mortimer Peter G.S. , Vassal Gilles , Geoerger Birgit
Published: February 2024

Representativeness of Study Participants
Supplementary Table S2 from Phase I/II Study of the WEE1 Inhibitor Adavosertib (AZD1775) in Combination with Carboplatin in Children with Advanced Malignancies: Arm C of the AcSé-ESMART Trial
Authors: Gatz Susanne A. , Harttrampf Anne C. , Brard Caroline , Bautista Francisco , André Nicolas , Abbou Samuel , Rubino Jonathan , Rondof Windy , Deloger Marc , Rübsam Marc , Marshall Lynley V. , Hübschmann Daniel , Nebchi Souad , Aerts Isabelle , Thebaud Estelle , De Carli Emilie , Defachelles Anne Sophie , Paoletti Xavier , Godin Robert , Miah Kowser , Mortimer Peter G.S. , Vassal Gilles , Geoerger Birgit
Published: February 2024

Table depicts amplification calling according to copy number alteration assessed in context of the ploidy
Supplementary Figure S1 from Phase I/II Study of the WEE1 Inhibitor Adavosertib (AZD1775) in Combination with Carboplatin in Children with Advanced Malignancies: Arm C of the AcSé-ESMART Trial
Authors: Gatz Susanne A. , Harttrampf Anne C. , Brard Caroline , Bautista Francisco , André Nicolas , Abbou Samuel , Rubino Jonathan , Rondof Windy , Deloger Marc , Rübsam Marc , Marshall Lynley V. , Hübschmann Daniel , Nebchi Souad , Aerts Isabelle , Thebaud Estelle , De Carli Emilie , Defachelles Anne Sophie , Paoletti Xavier , Godin Robert , Miah Kowser , Mortimer Peter G.S. , Vassal Gilles , Geoerger Birgit
Published: February 2024

Flow diagram of patients included
Supplementary Figures 1-3 from Tumor-Specific Activity of Precision Medicines in the NCI-MATCH Trial
Authors: Zhou Ivvone , Plana Deborah , Palmer Adam C.
Published: February 2024

Supplementary Figures 1-3.
Supplementary Figure S9 from Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden
Authors: Paz-Ares Luis , Garassino Marina Chiara , Chen Yuanbin , Reinmuth Niels , Hotta Katsuyuki , Poltoratskiy Artem , Trukhin Dmytro , Hochmair Maximilian J. , Özgüroğlu Mustafa , Ji Jun Ho , Statsenko Galina , Conev Nikolay , Bondarenko Igor , Havel Libor , Losonczy György , Xie Mingchao , Lai Zhongwu , Godin-Heymann Nadia , Mann Helen , Jiang Haiyi , Shrestha Yashaswi , Goldman Jonathan W.
Published: February 2024

Distribution of tTMB scores by treatment arm in the tTMB BEP.
Supplementary Figure S6 from Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden
Authors: Paz-Ares Luis , Garassino Marina Chiara , Chen Yuanbin , Reinmuth Niels , Hotta Katsuyuki , Poltoratskiy Artem , Trukhin Dmytro , Hochmair Maximilian J. , Özgüroğlu Mustafa , Ji Jun Ho , Statsenko Galina , Conev Nikolay , Bondarenko Igor , Havel Libor , Losonczy György , Xie Mingchao , Lai Zhongwu , Godin-Heymann Nadia , Mann Helen , Jiang Haiyi , Shrestha Yashaswi , Goldman Jonathan W.
Published: February 2024

Subgroup analysis of PFS by tTMB for (A) durvalumab plus tremelimumab plus EP versus EP and (B) durvalumab plus EP versus EP. In each panel, the shaded band shows the confidence interval for the ITT population; circle sizes are proportional to the number of events.