bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of mandated use early warning system tools on the development of nurses' higher‐order thinking: A systematic review
Authors: Flenady Tracy , Connor Justine , Byrne Amy‐Louise , Massey Deb , Le Lagadec Marie Danielle
Published: April 2024

Aim

Ascertain the impact of mandated use of early warning systems (EWSs) on the development of registered nurses' higher‐order thinking.

Design

A systematic literature review was conducted, following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines and checklist (Page et al., 2021).

Data Sources

CINAHL, Medline, Embase, PyscInfo.

Review Methods

Eligible articles were quality appraised using the MMAT tool. Data extraction was conducted independently by four reviewers. Three investigators thematically analysed the data.

Results

Our review found that EWSs can support or suppress the development of nurses' higher‐order thinking. EWS supports the development of higher‐order thinking in two ways; by confirming nurses' subjective clinical assessment of patients and/or by providing a rationale for the escalation of care. Of note, more experienced nurses expressed their view that junior nurses are inhibited from developing effective higher‐order thinking due to reliance on the tool.

Conclusion

EWSs facilitate early identification of clinical deterioration in hospitalised patients. The impact of EWSs on the development of nurses' higher‐order thinking is under‐explored. We found that EWSs can support and suppress nurses' higher‐order thinking. EWS as a supportive factor reinforces the development of nurses' heuristics, the mental shortcuts experienced clinicians call on when interpreting their subjective clinical assessment of patients. Conversely, EWS as a suppressive factor inhibits the development of nurses' higher‐order thinking and heuristics, restricting the development of muscle memory regarding similar presentations they may encounter in the future. Clinicians' ability to refine and expand on their catalogue of heuristics is important as it endorses the future provision of safe and effective care for patients who present with similar physiological signs and symptoms.

Impact

This research impacts health services and education providers as EWS and nurses' development of higher‐order thinking skills are essential aspects of delivering safe, quality care.

No Patient or Public Contribution

This is a systematic review, and therefore, comprises no contribution from patients or the public.
Insurance and economic growth nexus: A comprehensive exploration of the dynamic relationship and future research trajectories
Authors: Singh Dharmendra , Srivastava Abhay Kumar , Malik Garima , Yadav Anshul , Jain Prateek
Published: April 2024

Academic interest in insurance and economic growth nexus has prospered in the last two decades. There needs to be more review‐based research in this area. We, therefore, reviewed the literature and presented future research directions helpful for the further development of the research field. This literature review seeks to enrich the discourse on insurance and economic growth through a comprehensive and detailed review of 126 articles covering 96 journals from 2004 to 2023. Using Theory, Context, Characteristics, and Methods (TCCM), a detailed analysis has been conducted on the prominent theories, research context, key variables, and the methodologies and analysis techniques employed in the literature over the past 19 years. Through content analysis, we present the findings across three knowledge dimensions related to insurance and economic growth: research focus, country focus, and insurance focus. Our research sheds light on under‐researched contexts, variables, and analytical techniques.
The challenge of ecological validity in temporomandibular disorders research
Authors: Nickel Jeffrey C. , Gonzalez Yoly M. , Gallo Luigi M. , Iwasaki Laura R.
Published: April 2024

Objective

To review the ecological validity of outcomes from current research involving temporomandibular disorders (TMDs), with an emphasis on chronic myofascial pain and the precocious development of degenerative disease of the temporomandibular joint (TMJ).

Materials and Methods

Current approaches used to study TMDs in terms of neuromechanics, masticatory muscle behaviours, and the dynamics of the autonomic nervous system (ANS) were assessed for ecological validity in this review. In particular, the available literature was scrutinized regarding the effects of sampling, environmental and psychophysiological constraints and averaging data across biological rhythms.

Results

Validated computer‐assisted numerical modelling of the neuromechanics used biological objective functions to accurately predict muscle activation patterns for jaw‐loading tasks that were individual‐specific. With respect to masticatory muscle behaviour, current findings refute the premise that sustained bruxing and clenching at high jaw‐loading magnitudes were associated with painful TMDs such as myofascial pain. Concerning the role of the ANS in TMDs, there remains the need for personalized assessments based on biorhythms, and where the detection of dysregulated physiologic oscillators may inform interventions to relieve pain and restore normal function.

Conclusions

Future human research which focuses on TMD myofascial pain or the precocious development and progression of TMJ degenerative joint disease requires experimental designs with ecological validity that capture objectively measured data which meaningfully reflect circadian and ultradian states.
Typhoid fever in children in Goroka, Papua New Guinea
Authors: Ruape Whitney Ato , Mond Casparia , Toroi Watson , Max Becky , Chanoan Josephine , Duke Trevor
Published: April 2024

Background

Typhoid is endemic in many low‐income countries, including in Papua New Guinea. This study aimed to describe the burden and clinical features of typhoid in children in a provincial hospital, to describe environmental conditions that lead to typhoid, and to document the antibiotic sensitivity of Salmonella spp. in the Eastern Highlands Province.

Methods

A combined retrospective and prospective study of children admitted to with clinical features of typhoid to the Goroka Hospital throughout 2022.

Results

The study included 98 children, of which 54% were female. The median age was 8 (IQR 5–10.6) years. Over 60% of the patients were from Goroka District, the peri‐urban area encompassing the town and surrounds. Ninety‐four percent (92) of the patients used a pit latrine as a toilet and only 28% had access to treated water. Neuropsychiatric symptoms were common (60%), as was leukopenia (48%), thrombocytopenia (52%) and anaemia (42%). Thirty‐seven patients had positive blood cultures for Salmonella typhi; all isolates were sensitive to third‐generation cephalosporins, pefloxacin, ampicillin, trimethoprim and sulfamethoxazole, and only 54% sensitive to chloramphenicol. The median duration of hospitalisation was 6 days (IQR). There were no deaths.

Conclusion

Prompt public health actions are needed to reduce the burden of typhoid infection in the Papua New Guinea. The conjugate typhoid vaccine should be considered in the highlands region, where typhoid is most endemic.
Evaluation of antimicrobial purchasing by companion animal veterinary facilities in Canada, the United Kingdom, and the United States of America (2019‐2021)
Authors: Weese J. Scott , Mosher Margo , Low Rochelle , West Ellie , O'Kelley Ben , Morrison Jo Ann , Kimmerlein Anne , St. Bernard Silene , Blackie Kathrine , Gronlund Ulrika , Battersby Ian
Published: April 2024

Background

Measuring antimicrobial use is a core component of antimicrobial stewardship. Purchasing data may be easier to obtain than prescription data in some situations, but differences in clinic size, caseload and collection timeframes must be considered.

Objective

Our objective was to evaluate purchases of systemic antibacterial agents by small animal veterinary facilities in 5 networks across 3 countries, using a mg/veterinarian full time equivalent (FTE)/week as the metric.

Methods

Data were obtained from purchasing records of 2194 veterinary facilities from networks from the United States (US, n = 3: US‐A, 1036 facilities; US‐B, 101 facilities; US‐C, 886 facilities), Canada (n = 1: 117 facilities) and the United Kingdom (UK, n = 1: 54 facilities) during 2019‐2021.

Results

In total, 20 020 269 767 mg (20.02 t) of antimicrobials were purchased. Overall differences between the UK and North America were driven by significantly higher purchases of amoxicillin‐clavulanic acid in the UK (P < .001), with substantially less purchasing of third generation cephalosporins in the UK (P < .0001). A significant association was found between FTE and purchasing, with decreased purchasing (mg/FTE/week) as facility FTE increased. Significant differences also were found among US regions. Facilities in the top 10% of total purchasing accounted for 23%‐30% of purchases, compared to only 1.6%‐3.8% for the bottom 10%.

Conclusions and Clinical Importance

These data provide useful information about general purchasing trends, inter‐ and intraregional differences and differences among facility types and identify high purchasing outliers for further investigation.
Safety and biologic activity of a canineanti‐CD20monoclonal antibody in dogs with diffuse largeB‐celllymphoma
Authors: McLinden Gretchen P. , Avery Anne C. , Gardner Heather L. , Hughes Kelly , Rodday Angie M. , Liang Kexuan , London Cheryl A.
Published: April 2024

Background

To explore the safety and utility of combining low dose single‐agent doxorubicin with a canine specific anti‐CD20 monoclonal antibody (1E4‐cIgGB) in client owned dogs with untreated B‐cell lymphoma.

Animals

Forty‐two client‐owned dogs with untreated B‐cell lymphoma.

Methods

A prospective, single arm, open label clinical trial of dogs with B‐cell lymphoma were enrolled to receive 1E4‐cIgGB and doxorubicin in addition to 1 of 3 immunomodulatory regimens. B‐cell depletion was monitored by flow cytometry performed on peripheral blood samples at each visit.

Results

Dogs demonstrated a statistically significant depletion in CD21+ B‐cells 7 days following the first antibody infusion (median fraction of baseline at 7 days = 0.04,P < .01) that persisted throughout treatment (median fraction of baseline at 21 days = 0.01,P< .01) whereas CD5+ T‐cells remained unchanged (median fraction of baseline at 7 days = 1.05,P = .88; median fraction of baselie at 7 days = 0.79,P= .42; Figure 1; Supplemental Table 3). Recovery of B‐cells was delayed, with at Day 196, only 6/17 dogs (35%) remaining on the study had CD21+ counts >0.5 of baseline, indicating sustained B cell depletion at 4+ months after the final treatment. 1E4‐cIgGB was well tolerated with only 1 dog exhibiting a hypersensitivity event within minutes of the last antibody infusion.

Conclusions

The canine 1E4‐cIgGB anti‐CD20 monoclonal antibody is apparently safe when administered with doxorubicin and effectively depletes B‐cells in dogs with DLBCL.
Problems and strategies to maintain the existence of domestic registered patents in Indonesia to promote the economic growth
Authors: Amirulloh Muhamad , Muchtar Helitha Novianty
Published: April 2024

The number of acquisitions of Indonesian domestic patents is still low, while Article 130 letter d of Law Number 13 of 2016 concerning Patents regulates the abolition of patents due to the patent holder not fulfilling the obligation to pay the annual fee. This provision causes the loss of registered patent rights that have been hard to obtain, while the legal protection is still long, and there is still potential for commercialization value. It is feared that this will become one of the obstacles in the effort to increase the acquisition of domestic patents which in the end will also hamper Indonesia's economic growth. This article seeks to formulate the problems and strategies in maintaining the existence of domestically registered patents to be able to provide adequate protection for the exclusive rights of inventors while at the same time being able to support national economic growth.
Effective detection of BRAFV595E mutation in canine urothelial and prostate carcinomas using immunohistochemistry
Authors: Aeschlimann Leonore , Kehl Alexandra , Guscetti Franco , Posthaus Caroline , Aupperle‐Lellbach Heike , Rottenberg Sven , de Brot Simone
Published: April 2024

Canine urothelial carcinoma (UC) and prostate carcinoma (PC) frequently exhibit the BRAFV595E mutation, akin to the BRAFV600E mutation common in various human cancers. Since the initial discovery of the BRAF mutation in canine cancers in 2015, PCR has been the standard method for its detection in both liquid and tissue biopsies. Considering the similarity between the canine BRAFV595E and human BRAFV600E mutations, we hypothesized that immunohistochemistry (IHC) using a BRAFV600E‐specific antibody could effectively identify the canine mutant BRAFV595E protein. We tested 122 canine UC (bladder n = 108, urethra n = 14), 21 PC, and benign tissue using IHC and performed digital droplet PCR (ddPCR) on all 122 UC and on 14 IHC positive PC cases. The results from ddPCR and IHC were concordant in 99% (135/136) of the tumours. Using IHC, BRAFV595E was detected in 72/122 (59%) UC and 14/21 (65%) PC. Staining of all benign bladder and prostate tissues was negative. If present, mutant BRAF staining was homogenous, with rare intratumour heterogeneity in three (4%) cases of UC. Additionally, the BRAFV595E mutation was more prevalent in tumours with urothelial morphology, and less common in glandular PC or UC with divergent differentiation. This study establishes that BRAFV600‐specific IHC is a reliable and accurate method for detecting the mutant BRAFV595E protein in canine UC and PC. Moreover, the use of IHC, especially with tissue microarrays, provides a cost‐efficient test for large‐scale screening of canine cancers for the presence of BRAF mutations. This advancement paves the way for further research to define the prognostic and predictive role of this tumour marker in dogs and use IHC to stratify dogs for the treatment with BRAF inhibitors.
Mites in chocolate production system: A case study in southern Brazil
Authors: Silva Darliane Evangelho , Leão Da Silva Rita Tatiane , De Almeida Paz Neto Antônio , Martins Pinheiro Gizele , Granich Juliana , Juarez Ferla Noeli
Published: April 2024

This work aimed to recognize the mite fauna present in the different environments of a chocolate production system in Serra Gaúcha, Southern Brazil. The collections were carried out in August 2022 in different environments of an artisanal chocolate factory and store. Chocolate samples were collected from the store, the manufacturing process, the raw materials used to produce chocolates and the dust from the factory environments. Different collection methodologies were used depending on the materials' characteristics or environments. A total of 407 mites belonging to the families Acaridae, Anystidae, Blattisociidae, Cheyletidae, Glycyphagidae, Laelapidae, Pyemotidae, Tarsonemidae, Tetranychidae, Tydeidae, in addition to Oribatida and Uropodina, were collected. Tydeidae was most abundant, with 55% of the specimens found, with Brachytydeus oregonensis being the most representative, followed by Acaridae, with Tyrophagus putrescentiae representing 27.5% of the mites found.
Genomic factors shape carbon and nitrogen metabolic niche breadth across Saccharomycotina yeasts
Authors: Opulente Dana A. , LaBella Abigail Leavitt , Harrison Marie-Claire , Wolters John F. , Liu Chao , Li Yonglin , Kominek Jacek , Steenwyk Jacob L. , Stoneman Hayley R. , VanDenAvond Jenna , Miller Caroline R. , Langdon Quinn K. , Silva Margarida , Gonçalves Carla , Ubbelohde Emily J. , Li Yuanning , Buh Kelly V. , Jarzyna Martin , Haase Max A. B. , Rosa Carlos A. , ČCadež Neža , Libkind Diego , DeVirgilio Jeremy H. , Hulfachor Amanda Beth , Kurtzman Cletus P. , Sampaio José Paulo , Gonçalves Paula , Zhou Xiaofan , Shen Xing-Xing , Groenewald Marizeth , Rokas Antonis , Hittinger Chris Todd
Published: April 2024

Organisms exhibit extensive variation in ecological niche breadth, from very narrow (specialists) to very broad (generalists). Two general paradigms have been proposed to explain this variation: (i) trade-offs between performance efficiency and breadth and (ii) the joint influence of extrinsic (environmental) and intrinsic (genomic) factors. We assembled genomic, metabolic, and ecological data from nearly all known species of the ancient fungal subphylum Saccharomycotina (1154 yeast strains from 1051 species), grown in 24 different environmental conditions, to examine niche breadth evolution. We found that large differences in the breadth of carbon utilization traits between yeasts stem from intrinsic differences in genes encoding specific metabolic pathways, but we found limited evidence for trade-offs. These comprehensive data argue that intrinsic factors shape niche breadth variation in microbes.
Repair of CRISPR-guided RNA breaks enables site-specific RNA excision in human cells
Authors: Nemudraia Anna , Nemudryi Artem , Wiedenheft Blake
Published: April 2024

Genome editing with CRISPR RNA-guided endonucleases generates DNA breaks that are resolved by cellular DNA repair machinery. However, analogous methods to manipulate RNA remain unavailable. We show that site-specific RNA breaks generated with type-III CRISPR complexes are repaired in human cells and that this repair can be used for programmable deletions in human transcripts to restore gene function. Collectively, this work establishes a technology for precise RNA manipulation with potential therapeutic applications.
Corporate emissions targets and the neglect of future innovators
Authors: Robiou du Pont Yann , Rogelj Joeri , Hsu Angel , van Vuuren Detlef , Hoepner Andreas G. F.
Published: April 2024

Targets can distort competition in favor of incumbent firms
Sustainable justice
Sustainability for the Forgotten
Gary E. Machlis
University of Utah Press, 2024. 262 pp.
Authors: Berardi Andrea
Published: April 2024

The needs of marginalized groups must be central to sustainability goals, argues a sociologist
War: not an unlikely topic for science lessons
Authors: Erduran Sibel
Published: April 2024

As a seven-year-old child, I experienced war in Cyprus. Armed conflict has not been far from my conscience ever since. At a time when there are active conflicts in many parts of the world, war is unlikely to be far from many children’s minds globally today. Can a “war” theme be included in science lessons and play a role in helping young children develop into socially responsible scientists and peaceful citizens?
Tectonic geomorphology and Quaternary slip history of the Fuyun fault, southwestern Altai Mountains, central Asia
Authors: Wu Chen , Huang Ke , Yin An , Zhang Jinyu , Zuza Andrew V. , Haproff Peter J. , Ding Lin
Published: April 2024

The northwest-trending Altai Mountains of central Asia expose a complex network of thrust and strike-slip faults that are key features accommodating intracontinental crustal shortening related to the Cenozoic India-Asia collision. In this study, we investigated the Quaternary slip history of the Fuyun fault, a right-lateral strike-slip fault bounding the southwestern margin of the Altai Mountains, through geologic mapping, geomorphic surveying, and optically stimulated luminescence (OSL) geochronology. At the Kuoyibagaer site, the Fuyun fault displaces three generations of Pleistocene–Holocene fill-cut river terraces (i.e., T3, T2, and T1) containing landslide and debris-flow deposits. The right-lateral offsets are magnified by erosion of terrace risers, suggesting that river course migration has been faster than slip along the Fuyun fault. The highest Tp2 terrace was abandoned in the middle Pleistocene (150.4 ± 8.1 ka uppermost OSL age) and was displaced 145.5 +45.6/–12.1 m along the Fuyun fault, yielding a slip rate of 1.0 +0.4/–0.1 mm/yr since the middle Pleistocene. The lower Tp1 terrace was abandoned in the late Pleistocene and aggraded by landslides and debris flows in the latest Pleistocene–Holocene (36.7 ± 1.6 ka uppermost OSL age). Tp1 was displaced 67.5 +14.2/–6.1 m along the Fuyun fault, yielding a slip rate of 1.8 +0.5/–0.2 mm/yr since the late Pleistocene. Our preferred minimum slip rate of ~1 mm/yr suggests the Fuyun fault accommodates ~16% of the average geodetic velocity of ~6 mm/yr across the Altai Mountains. Integration of our new Fuyun slip rate with other published fault slip rates accounts for ~4.2 mm/yr of convergence across the Chinese Altai, or ~70% of the geodetic velocity field.
Use of GLP1 receptor agonists in early pregnancy and reproductive safety: a multicentre, observational, prospective cohort study based on the databases of six Teratology Information Services
Authors: Dao Kim , Shechtman Svetlana , Weber-Schoendorfer Corinna , Diav-Citrin Orna , Murad Reem Hegla , Berlin Maya , Hazan Ariela , Richardson Jonathan L , Eleftheriou Georgios , Rousson Valentin , Diezi Leonore , Haefliger David , Simões-Wüst Ana Paula , Addor Marie-Claude , Baud David , Lamine Faiza , Panchaud Alice , Buclin Thierry , Girardin François R , Winterfeld Ursula
Published: April 2024

Objectives

Glucagon-like peptide 1 receptor agonists (GLP1-RA) are indicated for the treatment of type 2 diabetes and more recently for weight loss. The aim of this study was to assess the risks associated with GLP1-RA exposure during early pregnancy.

Design

This multicentre, observational prospective cohort study compared pregnancy outcomes in women exposed to GLP1-RA in early pregnancy either for diabetes or obesity treatment with those in two reference groups: (1) women with diabetes exposed to at least one non-GLP1-RA antidiabetic drug during the first trimester and (2) a reference group of overweight/obese women without diabetes, between 2009 and 2022.

Setting

Data were collected from the databases of six Teratology Information Services.

Participants

This study included 168 pregnancies of women exposed to GLP1-RA during the first trimester, alongside a reference group of 156 pregnancies of women with diabetes and 163 pregnancies of overweight/obese women.

Results

Exposure to GLP1-RA in the first trimester was not associated with a risk of major birth defects when compared with diabetes (2.6% vs 2.3%; adjusted OR, 0.98 (95% CI, 0.16 to 5.82)) or to overweight/obese (2.6% vs 3.9%; adjusted OR 0.54 (0.11 to 2.75)). For the GLP1-RA group, cumulative incidence for live births, pregnancy losses and pregnancy terminations was 59%, 23% and 18%, respectively. In the diabetes reference group, corresponding estimates were 69%, 26% and 6%, while in the overweight/obese reference group, they were 63%, 29% and 8%, respectively. Cox proportional cause-specific hazard models indicated no increased risk of pregnancy losses in the GLP1-RA versus the diabetes and the overweight/obese reference groups, in both crude and adjusted analyses.

Conclusions

This study offers reassurance in cases of inadvertent exposure to GLP1-RA during the first trimester of pregnancy. Due to the limited sample size, larger studies are required to validate these findings.
Molecular-Induced Steric Shape Separation of Nano Geometries
Authors: Ahmad Imtiaz
Published: April 2024

The separation of specific-shaped nanoparticles from particle mixtures is important for the construction of particle domains with shape-specific characteristics. On the other hand, shape-based particle separation techniques have not received as much attention as size-based techniques. The shape separation effect of molecule-coated nanoparticles is primarily dependent on short-range steric interaction. The surfactant’s geometrical arrangement determines the position of the nanoparticle’s various crystallographic facets; this also determines how the various shapes are organized throughout the nanoparticle self-assembly process. In addition to smooth surfaces with a fixed droplet contact line and a stable environment, the self-assembled shape separation effect has been observed on surfaces with wettability stripe patterns and fluctuating environments where the droplet contact line behaves stick–slip-like during the evaporation process. The shape separation of spheres and rods is strongly influenced by steric interactions. Since shape-dependent transport properties exist in such nano-crystalline domains, it is important to understand the shape separation effect.
You Only Need One Thing One Click: Self-Training for Weakly Supervised 3D Scene Understanding
Authors: Liu Zhengzhe , Qi Xiaojuan , Fu Chi-Wing
Published: April 2024

Understanding 3D scenes, such as semantic segmentation and instance identification within point clouds, typically demands extensive annotated datasets. However, generating point-by-point labels is an overly laborious process. While recent techniques have been developed to train 3D networks with a minimal fraction of labeled points, our method, dubbed “One Thing One Click,” simplifies this by requiring just a single label per object. To effectively utilize these sparse annotations during network training, we’ve crafted an innovative self-training strategy. This involves alternating between training phases and label spreading, powered by a graph propagation module. Additionally, we integrate a relation network to create category-specific prototypes, improving pseudo label accuracy and steering the training process. Our approach also seamlessly integrates with 3D instance segmentation, incorporating a point-clustering technique. Our method demonstrates superior performance over other weakly supervised strategies for 3D semantic and instance segmentation, as evidenced by tests on both ScanNet-v2 and S3DIS datasets. Remarkably, the efficacy of our self-training method with limited annotations rivals that of fully supervised models. Codes and models are available at https://github.com/liuzhengzhe/One-Thing-One-Click .
Assessing soil contamination by potentially toxic elements in artisanal and small-scale gold mining sites of the Adamawa Region, Cameroon
Authors: Danala Danga S. , Ekengele Nga L. , Makhubela T. V. , Ibrahim B. , Bitom D. L. , Kramers J. D.
Published: April 2024

Gold mining is acknowledged as a principal source of environmental contamination, primarily due to the release of potentially toxic elements (PTEs) through tailings dispersion into adjacent soils. Such contamination leads to land degradation, pollution, biodiversity loss and soil contamination, and subsequently impacts the food chain, human health and soil ecosystems. This study evaluates the extent of PTE contamination in soils at artisanal and small-scale gold mining (ASGM) sites within the Meiganga area of the Adamawa-Yade Domain, Cameroon. ASGM extraction processes from quartz veins in this area involve the removal of topsoil to access the ore. Comparative analysis of soil samples from three profiles within the mining zone were conducted to determine contamination levels using pollution indices: enrichment factor, geoaccumulation index, contamination factor and pollution load index. Results indicate higher concentrations of PTEs in soils from the mining area compared to the control profile, with notable contamination in the bottom slope profiles and B horizons, reflecting considerable metal accumulation. The contamination levels of PTEs substantially exceed background levels in the upper continental crust. The study attributes the elevated concentrations of PTEs not only to local mineralization but also to anthropic activities, particularly ASGM, which contributes to their enrichment, distribution and mobility. This pronounced contamination necessitates immediate intervention, advocating for pollution-control measures to address potential ecosystem and human health risks. It highlights the environmental toll of ASGM and underscores the imperative for sustainable mining practices and effective soil remediation techniques, including phytoremediation and soil replacement, to alleviate the adverse effects.
We don't know when plate tectonics began
Authors: Harrison T. Mark
Published: April 2024

Geologists have speculated when plate tectonics began since the dawn of that revolution, with recent estimates ranging from the last 20% of Earth history to within the first 5%. All such estimates rest on six types of evidence: preservation of modern plate-tectonic features, detrital zircon age spectra, trace element and isotope geochemistry, atmosphere–crust–mantle exchange, palaeomagnetism and model calculations. ‘Burke's Law’ suggests that the null hypothesis puts the onus on demonstrating when plate tectonics was not operating rather than requiring observation of plate-tectonic features in the geological record, as assemblages presumed characteristic of plate tectonics could be lost from the geological record (owing to preservation biases) or never existed (owing to secular changes). This issue has become salient as our community appears to be coalescing around the paradigm that plate tectonics began during the late Archean in the face of problematic evidence, in much the same way it has done repeatedly over the past century (e.g. rejecting continental drift but accepting geosyncline theory). I summarize evidence from the six evidentiary types and conclude that we do not know when plate tectonics initiated. Claiming we do forestalls the day when we might truly understand an event at the heart of Earth history and habitability.
Structure and Mechanisms of Assembly-Line Polyketide Synthases
Authors: Soohoo Alexander M. , Cogan Dillon P. , Brodsky Krystal L. , Khosla Chaitan
Published: April 2024

Three decades of studies on the multifunctional 6-deoxyerythronolide B synthase have laid a foundation for understanding the chemistry and evolution of polyketide antibiotic biosynthesis by a large family of versatile enzymatic assembly lines. Recent progress in applying chemical and structural biology tools to this prototypical assembly-line polyketide synthase (PKS) and related systems has highlighted several features of their catalytic cycles and associated protein dynamics. There is compelling evidence that multiple mechanisms have evolved in this enzyme family to channel growing polyketide chains along uniquely defined sequences of 10–100 active sites, each of which is used only once in the overall catalytic cycle of an assembly-line PKS. Looking forward, one anticipates major advances in our understanding of the mechanisms by which the free energy of a repetitive Claisen-like reaction is harnessed to guide the growing polyketide chain along the assembly line in a manner that is kinetically robust yet evolutionarily adaptable.
Critical Mineral Separations: Opportunities for Membrane Materials and Processes to Advance Sustainable Economies and Secure Supplies
Authors: Lair Laurianne , Ouimet Jonathan Aubuchon , Dougher Molly , Boudouris Bryan W. , Dowling Alexander W. , Phillip William A.
Published: April 2024

Sustainable energy solutions and electrification are driving increased demand for critical minerals. Unfortunately, current mineral processing techniques are resource intensive, use large quantities of hazardous chemicals, and occur at centralized facilities to realize economies of scale. These aspects of existing technologies are at odds with the sustainability goals driving increased demand for critical minerals. Here, we argue that the small footprint and modular nature of membrane technologies position them well to address declining concentrations in ores and brines, the variable feed concentrations encountered in recycling, and the environmental issues associated with current separation processes; thus, membrane technologies provide new sustainable pathways to strengthening resilient critical mineral supply chains. The success of creating circular economies hinges on overcoming diverse barriers across the molecular to infrastructure scales. As such, solving these challenges requires the convergence of research across disciplines rather than isolated innovations.
Persistent neuroinflammation and functional deficits in a murine model of decompression sickness
Authors: Bhat Abid R. , Arya Awadhesh K. , Bhopale Veena M. , Imtiyaz Zuha , Xu Su , Bedir Dilara , Thom Stephen R.
Published: April 2024

Elevated glymphatic flow due to astrocyte and microglial activation from high-pressure exposure triggers release of microparticles (MPs) to the circulation where neutrophil activation and production of filamentous (F)-actin expressing MPs result in a persistent feed-forward neuroinflammatory cycle and functional deficits lasting for at least 12 days.
Interest of Chest CT to Assess the Prognosis of SARS-CoV-2 Pneumonia: An In-Hospital-Based Experience in Sub-Saharan Africa
Authors: Obe -A- Ndzem Holenn Serge Emmanuel , Mazoba Tacite Kpanya , Mukanga Désiré Yaya , Zokere Tyna Bongosepe , Lungela Djo , Makulo Jean-Robert , Ahuka Steve , Mbongo Angèle Tanzia , Molua Antoine Aundu
Published: April 2024

Background and Objectives. The chest computed tomography (chest CT) has played an important role in the management of COVID-19. Few data on its use in sub-Saharan Africa (SSA) are reported. The objectives of this study conducted in Kinshasa, DR Congo, were to describe the lung lesions on day 1 of hospitalization in patients admitted for suspected COVID-19 and to identify those that were most associated with SARS-CoV-2 infection/RT-PCR and the determinants of chest CT associated with death. Methods. We included all patients with respiratory symptoms (dyspnea, fever, and cough) and/or respiratory failure admitted to the SOS Médecins de nuit SARL hospital, DR Congo, during the 2nd and 3rd waves of the COVID-19 pandemic. The diagnosis of COVID-19 was established based on RT-PCR anti-SARS-CoV-2 tests (G1 (RT-PCR positive) vs. G2 (RT-PCR negative)), and all patients had a chest CT on the day of admission. We retrieved the digital files of patients, precisely the clinical, biological, and chest CT parameters of the day of admission as well as the vital outcome (survival or death). Chest CT were read by a very high-definition console using Advantage Windows software and exported to the hospital network using the RadiAnt DICOM viewer. To determine the threshold for the percentage of lung lesions associated with all-cause mortality, we used ROC curves. Factors associated with death, including chest CT parameters, were investigated using logistic regression analysis. Results. The study included 200 patients (average age 56.2±15.2 years; 19% diabetics and 4.5% obese), and COVID-19 was confirmed among 56% of them (G1). Chest CT showed that ground glass (72.3 vs. 39.8%), crazy paving (69.6 vs. 17.0%), and consolidation (83.9 vs. 22.7%), with bilateral and peripheral locations (68.8 vs. 30.7%), were more frequent in G1 vs. G2 (p<0.001). No case of pulmonary embolism and fibrosis had been documented. The lung lesions affecting 30% of the parenchyma were informative in predicting death (area under the ROC curve at 0.705, p=0.017). In multivariate analysis, a percentage of lesions affecting 50% of the lung parenchyma increased the risk of dying by 7.194 (1.656-31.250). Conclusion. The chest CT demonstrated certain characteristic lesions more frequently in patients in whom the diagnosis of COVID-19 was confirmed. The extent of lesions affecting at least half of the lung parenchyma from the first day of admission to hospital increases the risk of death by a factor of 7.
Serum Lipid Levels, Genetic Risk, and Lung Cancer Incidence: A Large Prospective Cohort Study
Authors: Wang Jing , Wang Qi , Shi Ziwei , Yan Xiaolong , Lei Zhiqun , Zhu Wenmin
Published: April 2024

Background:

Previous studies usually focused on the separate association of metabolism or genetic factors with lung cancer risk and have largely ignored their combined effect. We aimed to examine the associations between serum lipid levels, genetic risk, and lung cancer risk.

Methods:

A total of 426,524 participants of the UK Biobank were included. The Cox proportional hazards models and restricted cubic splines were performed to assess the association between serum lipid and lung cancer risk. Polygenic risk score (PRS) was constructed to assess its joint effect and interaction with serum lipid on lung cancer risk.

Results:

Higher level of apolipoprotein A was significantly correlated with lower lung cancer risk. An inverse-J-shaped relationship between high-density lipoprotein (HDL) and incident lung cancer was found. Individuals with low total cholesterol, HDL, low-density lipoprotein (LDL), apolipoprotein A, and apolipoprotein B, combined with high PRS, showed significantly elevated lung cancer risks. Compared to those with low PRS and low triglycerides, participants with high PRS and elevated triglyceride levels had a notably higher risk. The interaction effect of high PRS and low LDL [relative excess risk due to the interaction (RERI): 0.25, 95% confidence interval, 0.04–0.46], as well as the interaction effect of high PRS and low apolipoprotein B (RERI: 0.28, 95% confidence interval, 0.07–0.48), were both greater than the sum of their individual effects on lung cancer risk.

Conclusions:

Serum lipids were associated with lung cancer risk. LDL or apolipoprotein B interacting with genetic risk may affect lung cancer risk.

Impact:

Our findings emphasize the need for individuals with heightened genetic risk should pay more attention to their lipid levels to reduce lung cancer risk.
Sequencing of Anti-CD19 Therapies in the Management of Diffuse Large B-Cell Lymphoma
Authors: Lownik Joseph , Boiarsky Jonathan , Birhiray Ruemu , Merchant Akil , Mead Monica
Published: April 2024

Several second- and third-line immunotherapeutic options for patients with relapsed or refractory diffuse large B-cell lymphoma ineligible for autologous stem cell transplant are directed against the B-cell antigen cluster of differentiation 19 (CD19). The anti–CD19 monoclonal antibody tafasitamab, paired with the immunomodulator lenalidomide, mediates antibody-dependent cellular toxicity and phagocytosis; the antibody–drug conjugate loncastuximab tesirine delivers the DNA cross-linking agent tesirine via CD19 binding and internalization; and CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) products are engineered from autologous T cells. Although CD19 expression is assessed at diagnosis, clinically relevant thresholds of CD19 expression—which may not be detectable using current routine methodologies—have not been defined and may vary between CD19-directed treatment modalities. Determining optimal treatment sequencing strategies for CD19-directed therapy is hampered by the exclusion of patients who have received prior CD19-directed therapies from major clinical trials. Antigen escape, which is attributed to mechanisms including epitope loss and defective cell surface trafficking of CD19, is an important cause of CAR-T failure. Limited data suggest that CD19 expression may be maintained after non–CAR-T CD19-directed therapy, and retrospective analyses indicate that some patients with disease relapse after CAR-T may benefit from subsequent CD19-directed therapy. To date, clinical evidence on the effect of anti-CD19 therapy prior to CAR-T has been limited to small case series. Prospective studies and detailed analyses are needed to understand how pretreatment and posttreatment CD19 expression correlates with clinical responses to subsequent CD19-directed therapy to fully maximize treatment strategies.
FIGURE 3 from Impact of Surgery-Induced Myeloid-derived Suppressor Cells and the NOX2/ROS Axis on Postoperative Survival in Human Pancreatic Cancer
Authors: Grauers Wiktorin Hanna , Aydin Ebru , Kiffin Roberta , Vilhav Caroline , Bourghardt Fagman Johan , Kaya Mustafa , Paul Sanchari , Westman Beatrice , Bratlie Svein Olav , Naredi Peter , Hellstrand Kristoffer , Martner Anna
Published: April 2024

High levels of M-MDSC and low levels of NKp30high NK cells after pancreatic cancer surgery correlate and predict poor survival. A, Forest plots for postoperative survival were generated by log-rank tests where patients were dichotomized on the basis of Youden index for high or low absolute number of M-MDSCs, CD56bright NK cells, CD16+ NK cells, monocytes, lymphocytes, CD8+ T cells, regulatory T cells, CD4+ T cells, DC, neutrophils, or plasma levels of IL6, high expression level of NKp30+ cells among CD16+ (NKp30high CD16+) and CD56bright (NKp30high CD56bright) NK cells one day after surgery or by age or sex. Kaplan–Meier survival comparisons by high (red) or low (blue) absolute numbers of M-MDSC (B) and NKp30high cells among CD16+ NK cells (C) one day after surgery by log-rank test. D, Heat map of correlations (Pearson r, above the diagonal) between immune cell populations and IL6 among patients undergoing pancreatic cancer surgery. P-values corresponding to each correlation are shown below the diagonal. Correlation between absolute numbers of M-MDSC and frequencies of NKp30high cells among CD16+ NK cells at all analyzed timepoints (E), or within the first week after surgery (green dots: pre-op, black dots: 1 day, red dots 3–5 days and orange dots 28 days after surgery; F). Statistics by linear regression. Survival impact of high (red) or low (black) intratumoral NCF2 expression in pancreas cancer samples from the IPEP study (n = 14; G) or the Kaplan–Meier plotter database (n = 852; H), using the best cut-off feature of the portal and log-rank statistics. I, Expression analysis of Single Cell portal PDAC samples showed that the majority of NCF2-expressing cells were confined to a specific immune cell cluster.
Data from Impact of Surgery-Induced Myeloid-derived Suppressor Cells and the NOX2/ROS Axis on Postoperative Survival in Human Pancreatic Cancer
Authors: Grauers Wiktorin Hanna , Aydin Ebru , Kiffin Roberta , Vilhav Caroline , Bourghardt Fagman Johan , Kaya Mustafa , Paul Sanchari , Westman Beatrice , Bratlie Svein Olav , Naredi Peter , Hellstrand Kristoffer , Martner Anna
Published: April 2024

Abstract
Preclinical studies imply that surgery triggers inflammation that may entail tumor outgrowth and metastasis. The potential impact of surgery-induced inflammation in human pancreatic cancer is insufficiently explored. This study included 17 patients with periampullary cancer [pancreatic ductal adenocarcinoma (PDAC) n = 14, ampullary carcinoma n = 2, cholangiocarcinoma n = 1] undergoing major pancreatic cancer surgery with curative intent. We analyzed the potential impact of preoperative and postoperative immune phenotypes and function on postoperative survival with >30 months follow-up. The surgery entailed prompt expansion of monocytic myeloid-derived suppressor cells (M-MDSC) that generated NOX2-derived reactive oxygen species (ROS). Strong induction of immunosuppressive M-MDSC after surgery predicted poor postoperative survival and coincided with reduced functionality of circulating natural killer (NK) cells. The negative impact of surgery-induced M-MDSC on survival remained significant in separate analysis of patients with PDAC. M-MDSC–like cells isolated from patients after surgery significantly suppressed NK cell function ex vivo, which was reversed by inhibition of NOX2-derived ROS. High NOX2 subunit expression within resected tumors from patients with PDAC correlated with poor survival whereas high expression of markers of cytotoxic cells associated with longer survival. The surgery-induced myeloid inflammation was recapitulated in vivo in a murine model of NK cell–dependent metastasis. Surgical stress thus induced systemic accumulation of M-MDSC–like cells and promoted metastasis of NK cell–sensitive tumor cells. Genetic or pharmacologic suppression of NOX2 reduced surgery-induced inflammation and distant metastasis in this model. We propose that NOX2-derived ROS generated by surgery-induced M-MDSC may be targeted for improved outcome after pancreatic cancer surgery.
Significance:
Pancreatic cancer surgery triggered pronounced accumulation of NOX2+ myeloid-derived suppressor cells that inhibited NK cell function and negatively prognosticated postoperative patient survival. We propose the targeting of M-MDSC as a conceivable strategy to reduce postoperative immunosuppression in pancreatic cancer.
Spatial Atlas for Mapping Vascular Microcalcification Using 18F-NaF PET/CT: Application in Hyperphosphatemic Familial Tumoral Calcinosis
Authors: Sheppard Aaron J. , Theng Elizabeth H. , Paravastu Sriram S. , Wojnowski Natalia M. , Farhadi Faraz , Morris Michael A. , Hartley Iris R. , Gafni Rachel I. , Roszko Kelly L. , Collins Michael T. , Saboury Babak
Published: April 2024

BACKGROUND:

Vascular calcification causes significant morbidity and occurs frequently in diseases of calcium/phosphate imbalance. Radiolabeled sodium fluoride positron emission tomography/computed tomography has emerged as a sensitive and specific method for detecting and quantifying active microcalcifications. We developed a novel technique to quantify and map total vasculature microcalcification to a common space, allowing simultaneous assessment of global disease burden and precise tracking of site-specific microcalcifications across time and individuals.

METHODS:

To develop this technique, 4 patients with hyperphosphatemic familial tumoral calcinosis, a monogenic disorder of FGF23 (fibroblast growth factor-23) deficiency with a high prevalence of vascular calcification, underwent radiolabeled sodium fluoride positron emission tomography/computed tomography imaging. One patient received serial imaging 1 year after treatment with an IL-1 (interleukin-1) antagonist. A radiolabeled sodium fluoride–based microcalcification score, as well as calcification volume, was computed at all perpendicular slices, which were then mapped onto a standardized vascular atlas. Segment-wise mCS
mean
and mCS
max
were computed to compare microcalcification score levels at predefined vascular segments within subjects.

RESULTS:

Patients with hyperphosphatemic familial tumoral calcinosis had notable peaks in microcalcification score near the aortic bifurcation and distal femoral arteries, compared with a control subject who had uniform distribution of vascular radiolabeled sodium fluoride uptake. This technique also identified microcalcification in a 17-year-old patient, who had no computed tomography–defined calcification. This technique could not only detect a decrease in microcalcification score throughout the patient treated with an IL-1 antagonist but it also identified anatomic areas that had increased responsiveness while there was no change in computed tomography–defined macrocalcification after treatment.

CONCLUSIONS:

This technique affords the ability to visualize spatial patterns of the active microcalcification process in the peripheral vasculature. Further, this technique affords the ability to track microcalcifications at precise locations not only across time but also across subjects. This technique is readily adaptable to other diseases of vascular calcification and may represent a significant advance in the field of vascular biology.