bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and experimental analysis of magneto-rheological damper featuring a labyrinthic dual-channel valve
Authors: Yang Xiaolong , Li Xue , Li Yan , Zhu Jiehong
Published: March 2024

For the sake of improving the damping performance of the cab suspension system, the MR damper featuring the labyrinthic dual-channel valve (LDCV-MRD for short) is proposed in this paper, which is composed of a mixture of circular channel, circular disk channel and circular tube channel. The LDCV-MRD is designed structurally and the magnetic circuit is analyzed. The output damping force mathematical model is established, and the coil’s number of turns is computed. The magnetic field in the damping channel of LDCV-MRD is simulated and analyzed. The processed and fabricated LDCV-MRD is tested, and the experimental results are compared and analyzed with the simulation results. The results show that the simulated values of the maximum damping force and the adjustable coefficient fit well with the experimental results. The peak output damping force of the experiment achieves 21 008 N. The adjustable coefficient reaches about 5.61, when the input current gets to 2 A.
Electrochemical deposition of nickel sulfide catalysts on commercial carbon rods as low-cost electrodes for hydrogen generation
Authors: Nguyen Khang Nhat , Bui Thach Khac , Nguyen Khanh Quang , Pham Viet Van
Published: March 2024

Nowadays, the challenge of the world and the scientific community is to find and effectively use renewable energy sources. One of the renewable energy research subjects that has been hotly discussed recently is the water-splitting reaction to produce hydrogen. In this study, we focus on fabricating nickel sulfide (NiS) materials deposited on commercial carbon rod (CR) substrates and using them as electrodes for the electrochemical water-splitting reaction to produce hydrogen gas. In detail, NiS materials were decorated on commercial carbon rods (NiS/CR) by cyclic voltammetry electrochemical deposition with a potential range from 0.2 to −1.2 V (versus Ag/AgCl), a scan rate of 10 mV s−1, and 15 cycles. Benefiting a strong interfacial synergetic effect based on NiS/CR materials shows an excellent electrocatalytic activity for hydrogen evolution reaction (HER). Specifically, the NiS/CR electrode exhibits a high performance with low overpotential (70 mV for HER) and a slight Tafel slope (50 mV dec−1). Besides, annealing temperature helps increase the crystal properties, causing the appearance of NiS2 and Ni3S2 phases in NiS/CR@400 samples. Interestingly, the electrochemical surface area (ESCA) of the NiS/CR@400 sample significantly increased (17.3%) compared to the NiS/CR sample (5.8% of the total physical surface area) is due to the presence of NiS2 and Ni3S2, leading to NiS/CR@400 sample enhances the active sites by 16.0 mF cm−2. Furthermore, the long-term durability of NiS/CR@400 electrodes is good electrocatalytic over a continuous cycling 12-hour operation at 20 mA cm−2 in an alkaline environment. The NiS/CR is a promising electrode candidate for high HER performance, and here is a new design of electrocatalysts for water splitting.
A photoluminescence and colorimetric dual-active mode of copper-modified carbon dots for quantitative sensing of histamine
Authors: Ahmad Musbahu Adam , Ulfa Desita Kamila , Sakti Satya Candra Wibawa , Khasanah Miratul , Wibrianto Aswandi , Sugito Siti Febtria Asrini , Chang Jia-yaw , Fahmi Mochamad Zakki
Published: March 2024

Determination of the histamine in food is a crucial aspect regarding its safety issue. The present study reported the preparation of copper-doped carbon dots (Cu-CDs) through the pyrolysis method and further applied them for sensitive histamine detection via UV–vis absorption and photoluminescence (PL) techniques. Several characterizations, including X-ray diffraction, Raman, Infrared, and photoluminescence spectra, confirmed this nanomaterial’s well-formed Cu-CDs and all-optical properties. While Photoluminescence spectra perform regular degradation of Cu-CDs emission, the absorption spectra also showed increasing peaks at 270 nm following the enhancement of histamine concentration introduced to Cu-CDs. The analytical method parameters were next used to evaluate histamine detection performance, where the Cu-CDs showed good accuracy and selectivity for detecting histamine with LOD and LOQ values as low as 19.20 and 64 mg l−1, respectively. It also possessed a valuable recovery rate ranging from 89%–106%. Even though UV–vis Spectrophotometry successfully detected histamine, Cu-CDs maintained their photoluminescence properties, offering more distinct advantages, including low cost, simplicity, high sensitivity, and selectivity properties.
Quasilinearization variational iteration method for system of nonlinear ODEs
Authors: Sinha Vikash Kumar , Maroju Prashanth
Published: March 2024

In this manuscript, we discuss a new technique for solving system of nonlinear differential equations, which is a modification of the variation iteration method (VIM) implemented using the quasilinearization method and Adomian’s polynomial. The quasilinearization variational iteration method (QVIM) is the name given to this proposed method. The proposed method’s convergence analysis in Banach space is also discussed here. Three application problems, including the Genesio-Tesi system, are considered to test the applicability of our approach. We also discuss the case study of the chaotic and non-chaotic solutions of the Genesio-Tesi system (GTS). The convergence behaviour of the method is studied for various values of parameter x. To assess the viability and efficacy of QVIM, we compare it to the existing well-known Adomian decomposition method. The results show that the proposed method is highly efficient and simple to implement.
The influence mechanism of Halbach array magnetic field control on discharge channels in EDM
Authors: Qiu Zhiwei , Tang Jiajing , Li Zhengkai , Yin Mulong , Peng Weiye
Published: March 2024

The use of magnetic field to actively control Electrical Discharge Machining(EDM) can effectively improve the problems of low material removal rate and poor surface quality, but due to the limitation of materials, the magnetic induction intensity of permanent magnets after magnetization is not high, and the magnetic induction lines of permanent magnets are too concentrated and difficult to control. In order to overcome the above shortcomings, this study applied the Halbach array magnetic field to the field of EDM for the first time, established a model of the trajectory of the charged particle beam in the discharge channel, analyzed the influence of the Halbach array magnetic field on the discharge channel, and clarified the improvement mechanism of the Halbacch array magnetic field in EDM. In addition, several sets of experiments were carried out by controlling the distance between the workpiece and the working surface of the Halbach array permanent magnets. The experimental results show that when the distance between the workpiece and the working surface of the Halbach array permanent magnet is less than 10mm, the material erosion rate of the workpiece increases significantly, and the electrode loss rate and surface roughness decrease significantly. When the workpiece is 0mm away from the working surface, the material removal rate is increased by 18.18%, from 0.4513mm3/min to 0.5333mm3/min, the tool wear ratio is reduced by 46.87%, from 0.2587 to 0.13745 mm3/min, and the surface roughness is reduced by 39.56%, from 4.186 μm to 2.53 μm.
Impact of the COVID-19 pandemic on hospital episodes for falls and fractures associated with new-onset disability and frailty in England: a national cohort study
Authors: Thomas Seth , Littleboy Kathryn , Foubert Josephine , Nafilyan Vahe , Bannister Neil , Routen Ash , Morriss Richard , Khunti Kamlesh , Armstrong Natalie , Gray Laura J , Gordon Adam L
Published: March 2024

Background

Older people with frailty are at risk of harm from immobility or isolation, yet data about how COVID-19 lockdowns affected them are limited. Falls and fractures are easily measurable adverse outcomes correlated with frailty. We investigated whether English hospital admission rates for falls and fractures varied from the expected trajectory during the COVID-19 pandemic, and how these varied by frailty status.

Methods

NHS England Hospital Episode Statistics Admitted Patient Care data were analysed for observed versus predicted outcome rates for 24 January 2020 to 31 December 2021. An auto-regressive integrated moving average time-series model was trained using falls and fracture incidence data from 2013 to 2018 and validated using data from 2019. Models included national and age-, sex- and region-stratified forecasts. Outcome measures were hospital admissions for falls, fractures, and falls and fractures combined. Frailty was defined using the Hospital Frailty Risk Score.

Results

144,148,915 pre-pandemic hospital admissions were compared with 42,267,318 admissions after pandemic onset. For the whole population, falls and fracture rates were below predicted for the first period of national lockdown, followed by a rapid return to rates close to predicted. Thereafter, rates followed expected trends. For people living with frailty, however, falls and fractures increased above expected rates during periods of national lockdown and remained elevated throughout the study period. Effects of frailty were independent of age.

Conclusions

People living with frailty experienced increased fall and fracture rates above expected during and following periods of national lockdown. These remained persistently elevated throughout the study period.
Four distinct ipsilateral vestibular schwannomas: A case of mosaic NF2-related schwannomatosis
Authors: Tunkel Alexandra E , Youner Emily R , Barseghyan Hayk , Fu Yulong , Bhattacharya Surajit , Bornhorst Miriam , Monfared Ashkan S
Published: March 2024

Objectives

Distinguishing between sporadic and germline/mosaic NF2-related schwannomatosis is important to ensure that patients have appropriate long-term care. With this report, we describe a unique case of a patient with 4 ipsilateral schwannomas and identify a combination of sequencing modalities that can accurately diagnose mosaic NF2-related schwannomatosis.

Methods

We present a 32-year-old woman with a familial history of vestibular schwannoma in her father and right-sided schwannomas involving the apical and basal turns of cochlea, lateral semicircular canal, and internal auditory canal (IAC). Genetic analysis of blood and frozen tissue from 2 tumors (intralabyrinthine and IAC tumors) was performed using next-generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), and optical genome mapping (OGM).

Results

Germline testing for NF2, LZTR1, and SMARCB1 was negative. Tumor genetic testing revealed a shared NF2 pathogenic variant between the 2 tumors (“first hit”) but distinct “second hit” NF2 variants, including mosaic loss of chromosome 22 in the IAC tumor seen only with OGM, consistent with mosaic NF2-related schwannomatosis.

Conclusions

Multimodality sequencing, including NGS, MLPA, and OGM, was required to ensure appropriate diagnosis of mosaic NF2-related schwannomatosis in this patient. A similar approach can be used for other patients with multiple ipsilateral tumors and suspected tumor predisposition.
Interobserver reproducibility of cervical histology interpretation with and without p16 immunohistochemistry
Authors: Tao Amy S , Zuna Rosemary , Darragh Teresa M , Grabe Niels , Lahrmann Bernd , Clarke Megan A , Wentzensen Nicolas
Published: March 2024

Objectives

Histopathological diagnosis of colposcopically identified cervical lesions is a critical step for the recognition of cervical cancer precursors requiring treatment. Although there have been efforts to standardize the histologic diagnosis of cervical biopsy specimens, in terms of terminology and use of biomarkers, there is no uniform approach in the pathology community. Adjunctive p16 immunohistochemistry (IHC) can highlight precancer diagnoses, with use recommendations outlined by the Lower Anogenital Squamous Terminology project.

Methods

We assessed the diagnostic reproducibility of cervical histopathological biopsy specimens with and without p16 staining among 2 expert pathologists.

Results

Interpretation of p16 IHC as positive vs negative was highly reproducible (92.5% agreement, κ = 0.85); greater variation was seen in the choice of which biopsy specimens required adjunctive p16 staining (78.0% agreement, κ = 0.43). Adjunctive p16 IHC did not significantly increase diagnostic agreement under multitiered grading systems (benign vs cervical intraepithelial neoplasia [CIN] 1/low-grade squamous intraepithelial lesion vs atypical squamous metaplasia vs CIN2/high-grade squamous intraepithelial lesion [HSIL] vs CIN3/HSIL-CIN3 vs cancer) (65.5% agreement, κ = 0.56 without p16; 70.0% agreement, κ = 0.58 with p16). However, when dichotomizing diagnoses based on clinical management (less than HSIL vs HSIL+), diagnostic agreement increased with p16 IHC (90.5% agreement, κ = 0.79 without p16; 92.0% agreement, κ = 0.84 with p16). For biopsy specimens taken from women positive for human papillomavirus (HPV) type 16, agreement was similar with or without adjunctive p16 (κ = 0.80 without p16; κ = 0.78-0.80 with p16). In contrast, p16 IHC substantially improved diagnostic agreement for cervical biopsy specimens taken from women positive for other high-risk HPV strains, producing improvements in κ from 0.03 to 0.24.

Conclusions

Adjunctive p16 immunostaining provides useful information in the evaluation of cervical biopsies for precancer. In our study, we have demonstrated that it is highly reproducible between 2 pathologists, although the decision of which biopsies warrant its use is less so. Furthermore, although p16 IHC showed a limited increase in diagnostic reproducibility for all biopsies included in our study, it did demonstrate a more sizable gain in biopsies negative for HPV 16 but positive for other high-risk genotypes. Further studies are needed to clarify the role of p16 IHC and how it can be optimized for the detection of cervical precancer, particularly in HPV-vaccinated populations where types other than HPV 16 are relatively more important.
Phylogeny, biogeography and ecological diversification of New Caledonian palms (Arecaceae)
Authors: Pérez-Calle Victor , Bellot Sidonie , Kuhnhäuser Benedikt G , Pillon Yohan , Forest Félix , Leitch Ilia J , Baker William J
Published: March 2024

Background and Aims

The geographical origin and evolutionary mechanisms underpinning the rich and distinctive New Caledonian flora remain poorly understood. This is attributable to the complex geological past of the island and to the scarcity of well-resolved species-level phylogenies. Here, we infer phylogenetic relationships and divergence times of New Caledonian palms, which comprise 40 species. We use this framework to elucidate the biogeography of New Caledonian palm lineages and to explore how extant species might have formed.

Methods

A phylogenetic tree including 37 New Caledonian palm species and 77 relatives from tribe Areceae was inferred from 151 nuclear genes obtained by targeted sequencing. Fossil-calibrated divergence times were estimated and ancestral ranges inferred. Ancestral and extant ecological preferences in terms of elevation, precipitation and substrate were compared between New Caledonian sister species to explore their possible roles as drivers of speciation.

Key Results

New Caledonian palms form four well-supported clades, inside which relationships are well resolved. Our results support the current classification but suggest that Veillonia and Campecarpus should be resurrected and fail to clarify whether Rhopalostylidinae is sister to or nested in Basseliniinae. New Caledonian palm lineages are derived from New Guinean and Australian ancestors, which reached the island through at least three independent dispersal events between the Eocene and Miocene. Palms then dispersed out of New Caledonia at least five times, mainly towards Pacific islands. Geographical and ecological transitions associated with speciation events differed across time and genera. Substrate transitions were more frequently associated with older events than with younger ones.

Conclusions

Neighbouring areas and a mosaic of local habitats shaped the palm flora of New Caledonia, and the island played a significant role in generating palm diversity across the Pacific region. This new spatio-temporal framework will enable population-level ecological and genetic studies to unpick the mechanisms underpinning New Caledonian palm endemism.
The impact of temperature and a chemesthetic cooling agent on lingual roughness sensitivity
Authors: Ricci Sebastiano , Kim Min Sung , Simons Christopher T
Published: March 2024

Oral tactile sensitivity underpins food texture perception, but few studies have investigated mechanoreception in oral tissues. During food consumption, oral tissues are exposed to a wide range of temperatures and chemical entities. The objective of the present study was to assess the influence of thermal sensations on lingual roughness sensitivity. Just-noticeable difference thresholds (JNDs) were determined using the staircase method for surface roughness from stainless steel coupons (Ra; 0.177–0.465 µm). Thresholds were assessed when cooling or heating the metal stimuli (n = 32 subjects). Compared to the JND threshold obtained at an ambient stimulus temperature (21 °C: 0.055 ± 0.010 μm), a cold (8 °C) temperature significantly (P = 0.019) reduced tongue sensitivity (i.e. increased JND) to surface roughness (0.109 ± 0.016 μm, respectively) whereas warm and hot temperatures had no significant effect (35 °C: 0.084 ± 0.012 μm; 45 °C: 0.081 ± 0.011 μm). To assess whether the effect of cooling on roughness thresholds is TRPM8-dependent, we collected roughness thresholds in a second cohort of subjects (n = 27) following the lingual application of the cooling compound Evercool 190 (24.3 µM). Interestingly, when Evercool 190 was used to elicit the cold sensation, lingual roughness JNDs were unaffected compared to the control application of water (EC: 0.112 ± 0.016 μm; water: 0.102 ± 0.017 μm; P = 0.604). That lingual roughness sensitivity is decreased by cold temperature, but not chemicals evoking cold sensations, suggests the mechanism underpinning thermal modulation is not TRPM8 dependent.
Do patients with different craniofacial patterns have differences in upper airway volume? A systematic review with network meta-analysis
Authors: Altheer Charlotte , Papageorgiou Spyridon N , Antonarakis Gregory S , Papadopoulou Alexandra K
Published: March 2024

Background

Craniofacial skeletal discrepancies have been associated with upper airway dimensions.

Objective

To identify differences in upper airway volume across different sagittal and vertical skeletal patterns.

Search methods

Unrestricted literature searches in eight databases/registers for human studies until May 2023.

Selection criteria

Cross-sectional studies measuring upper airway volumes using three-dimensional imaging in healthy patients of different sagittal (Class I, Class II, and Class III) or vertical (normodivergent, hypodivergent, and hyperdivergent) craniofacial morphology.

Data collection and analysis

Duplicate independent study selection, data extraction, and risk of bias assessment. Random-effects frequentist network meta-analysis was performed followed by subgroup-analyses and assessment of the quality of clinical recommendations (confidence in effect estimates) with the CINeMA (Confidence in Network Meta-Analysis) approach.

Results

Seventy publications pertaining to 66 unique studies were included with 56 studies (5734 patients) contributing to meta-analyses. Statistically significant differences were found for total  pharyngeal airway volume, with Class II having decreased airway volume (−2256.06 mm3; 95% Confidence Interval [CI] −3201.61 to −1310.51 mm3) and Class III increased airway volume (1098.93 mm3; 95% CI 25.41 to 2172.45 mm3) compared to Class I. Significant airway volume reductions for Class II were localized mostly at the oropharynx, followed by the palatopharynx, and the glossopharynx. Significant airway volume increases for Class III were localized mostly at the oropharynx, followed by the intraoral cavity, and hypopharynx. Statistically significant differences according to vertical skeletal configuration were seen only for the oropharynx, where hyperdivergent patients had reduced volumes compared to normodivergent patients (−1716.77 mm3; 95% CI −3296.42 to −137.12 mm3). Airway differences for Class II and Class III configurations (compared to Class I) were more pronounced in adults than in children and the confidence for all estimates was very low according to CINeMA.

Conclusions

Considerable differences in upper airway volume were found between sagittal and vertical skeletal configurations. However, results should be interpreted with caution due to the high risk of bias, owing to the retrospective study design, inconsistencies in anatomic compartment boundaries used, samples of mixed children–adult patients, and incomplete reporting.

Clinical Trial Registration

PROSPERO (CRD42022366928).
Acute and Chronic Oak Decline in urban and forest ecosystems in Southern Italy
Authors: Carluccio Giambattista , Sabella Erika , Greco Davide , Vergine Marzia , Delle Donne Angelo Giovanni , Nutricati Eliana , Aprile Alessio , De Bellis Luigi , Luvisi Andrea
Published: March 2024

Since recently, a decline of holm oak (Quercus ilex L.) is observed in Salento (South Italy), this caused concern regarding the protection of native biodiversity and local forests. Symptomatic trees show browning of leaves, thinning of canopy, and loss of branches. The aim of this study was to understand the biotic factors involved in the observed decline. During the monitoring activity, the use of phenotypic descriptors highlighted the presence of two types of decline with distinct symptoms among oaks in rural and urban areas, which could be classified as Acute Oak Decline (AOD) and Chronic Oak Decline (COD), respectively. Following this, diagnostic analyses were carried out to assess the presence of various holm oak pathogens on twigs, trunk, and soil. These analyses revealed the presence of several Botryosphaeriaceae oak pathogens, present ubiquitously between the two environmental contexts, with Diplodia seriata being overall the most prevalent. Contrarily, bacteria associated with AOD were only present in the rural areas and included: Brenneria goodwinii, Gibbsiella quercinecans, and Rahnella victoriana. As far as known to the authors, this is the first time these pathogens have been found in the Mediterranean coastal regions. Lastly, soil analyses performed to detect the presence of Phytophthora cinnamomi were negative. Our results highlight the presence of several pathogens, which indicates that oak decline is a multifactorial phenomenon for which the predisposing, initial, and contributing factors are not yet known particularly for the recently described AOD and COD. Finally, the identification of AOD-related bacteria in Salento is a cause of concern for the need of urgent management actions aimed to contain their spread and to preserve the forest heritage of the region.
The potential and limitations of large language models in identification of the states of motivations for facilitating health behavior change
Authors: Bak Michelle , Chin Jessie
Published: March 2024

Importance

The study highlights the potential and limitations of the Large Language Models (LLMs) in recognizing different states of motivation to provide appropriate information for behavior change. Following the Transtheoretical Model (TTM), we identified the major gap of LLMs in responding to certain states of motivation through validated scenario studies, suggesting future directions of LLMs research for health promotion.

Objectives

The LLMs-based generative conversational agents (GAs) have shown success in identifying user intents semantically. Little is known about its capabilities to identify motivation states and provide appropriate information to facilitate behavior change progression.

Materials and Methods

We evaluated 3 GAs, ChatGPT, Google Bard, and Llama 2 in identifying motivation states following the TTM stages of change. GAs were evaluated using 25 validated scenarios with 5 health topics across 5 TTM stages. The relevance and completeness of the responses to cover the TTM processes to proceed to the next stage of change were assessed.

Results

3 GAs identified the motivation states in the preparation stage providing sufficient information to proceed to the action stage. The responses to the motivation states in the action and maintenance stages were good enough covering partial processes for individuals to initiate and maintain their changes in behavior. However, the GAs were not able to identify users’ motivation states in the precontemplation and contemplation stages providing irrelevant information, covering about 20%-30% of the processes.

Discussion

GAs are able to identify users’ motivation states and provide relevant information when individuals have established goals and commitments to take and maintain an action. However, individuals who are hesitant or ambivalent about behavior change are unlikely to receive sufficient and relevant guidance to proceed to the next stage of change.

Conclusion

The current GAs effectively identify motivation states of individuals with established goals but may lack support for those ambivalent towards behavior change.
Curiosities in the Far North
Authors: Ekman Mattias
Published: March 2024

According to conventional accounts of Norwegian museum history, Norway’s history of collecting began in the second half of the eighteenth century. However, this article, which is the first comprehensive investigation into Norway’s involvement with seventeenth-century collecting cultures, shows that the country’s museum and collecting history began more than a hundred years earlier. It addresses the question of infrastructure: namely, how Norway and Norwegians came into contact with Danish and other continental collectors and collections. While some networks engaged explicitly in the exchange of rarities, others were primarily administrative, diplomatic or mercantile in character, allowing curiosities – and also curiosity – to travel. The article seeks to portray a museal culture of seeing, finding, transmuting, collecting, communicating, distributing and publishing specimens and artefacts. It demonstrates how well integrated Norwegians and Norway were in the culture of Kunstkammern and cabinets of curiosities, and it concludes that Norway has been profoundly overlooked in the history of early modern collecting.
The radiation of nodulated Chamaecrista species from the rainforest into more diverse habitats has been accompanied by a reduction in growth form and a shift from fixation threads to symbiosomes
Authors: Casaes Patricia Alves , Ferreira dos Santos José Miguel , Silva Verônica Cordeiro , Rhem Mariana Ferreira Kruschewsky , Teixeira Cota Matheus Martins , de Faria Sergio Miana , Rando Juliana Gastaldello , James Euan K , Gross Eduardo
Published: March 2024

All non-Mimosoid nodulated genera in the legume subfamily Caesalpinioideae confine their rhizobial symbionts within cell wall-bound ‘fixation threads’ (FTs). The exception is the large genus Chamaecrista in which shrubs and subshrubs house their rhizobial bacteroids more intimately within symbiosomes, whereas large trees have FTs. This study aimed to unravel the evolutionary relationships between Chamaecrista growth habit, habitat, nodule bacteroid type, and rhizobial genotype. The growth habit, bacteroid anatomy, and rhizobial symbionts of 30 nodulated Chamaecrista species native to different biomes in the Brazilian state of Bahia, a major centre of diversity for the genus, was plotted onto an ITS-trnL-F-derived phylogeny of Chamaecrista. The bacteroids from most of the Chamaecrista species examined were enclosed in symbiosomes (SYM-type nodules), but those in arborescent species in the section Apoucouita, at the base of the genus, were enclosed in cell wall material containing homogalacturonan (HG) and cellulose (FT-type nodules). Most symbionts were Bradyrhizobium genotypes grouped according to the growth habits of their hosts, but the tree, C. eitenorum, was nodulated by Paraburkholderia. Chamaecrista has a range of growth habits that allow it to occupy several different biomes and to co-evolve with a wide range of (mainly) bradyrhizobial symbionts. FTs represent a less intimate symbiosis linked with nodulation losses, so the evolution of SYM-type nodules by most Chamaecrista species may have (i) aided the genus-wide retention of nodulation, and (ii) assisted in its rapid speciation and radiation out of the rainforest into more diverse and challenging habitats.
DNA variants detected in primary and metastatic lung adenocarcinoma: a case report and review of the literature
Authors: Kelly Christina , Raymond Caitlin , Han Song , Lin Youmin , Chen Linyijia , Huang Gengming , Dong Jianli
Published: March 2024

Non–small cell lung cancer (NSCLC) has been found to have recurrent genetic abnormalities, and novel therapies targeting these aberrations have improved patient survival. In this study, specimens from benign tissue, primary tumors, and brain metastases were obtained at autopsy from a 55-year-old White female patient diagnosed with NSCLC and were examined using next-generation sequencing (NGS) and chromosomal microarray assay (CMA). No genetic aberrations were noted in the benign tissue; however, NGS identified a mutation in the KRAS proto-oncogene, GTPase (KRAS): KRAS exon 2 p.G12D in primary and metastatic tumor specimens. We observed 7 DNA copy number aberrations (CNAs) in primary and metastatic tumor specimens; an additional 7 CNAs were exclusively detected in the metastatic tumor specimens. These DNA alterations may be genetic drivers in the pathogenesis of the tumor specimen from our patient and may serve as biomarkers for the classification and prognosis of NSCLC.
Indirect Correlative Light and Electron Microscopy (iCLEM): A Novel Pipeline for Multiscale Quantification of Structure From Molecules to Organs
Authors: Struckman Heather L , Moise Nicolae , Vanslembrouck Bieke , Rothacker Nathan , Chen Zhenhui , van Hengel Jolanda , Weinberg Seth H , Veeraraghavan Rengasayee
Published: March 2024

Correlative light and electron microscopy (CLEM) methods are powerful methods that combine molecular organization (from light microscopy) with ultrastructure (from electron microscopy). However, CLEM methods pose high cost/difficulty barriers to entry and have very low experimental throughput. Therefore, we have developed an indirect correlative light and electron microscopy (iCLEM) pipeline to sidestep the rate-limiting steps of CLEM (i.e., preparing and imaging the same samples on multiple microscopes) and correlate multiscale structural data gleaned from separate samples imaged using different modalities by exploiting biological structures identifiable by both light and electron microscopy as intrinsic fiducials. We demonstrate here an application of iCLEM, where we utilized gap junctions and mechanical junctions between muscle cells in the heart as intrinsic fiducials to correlate ultrastructural measurements from transmission electron microscopy (TEM), and focused ion beam scanning electron microscopy (FIB-SEM) with molecular organization from confocal microscopy and single molecule localization microscopy (SMLM). We further demonstrate how iCLEM can be integrated with computational modeling to discover structure–function relationships. Thus, we present iCLEM as a novel approach that complements existing CLEM methods and provides a generalizable framework that can be applied to any set of imaging modalities, provided suitable intrinsic fiducials can be identified.
Emergence of an Orphan Nitrogenase Protein Following Atmospheric Oxygenation
Authors: Cuevas-Zuviría Bruno , Garcia Amanda K , Rivier Alex J , Rucker Holly R , Carruthers Brooke M , Kaçar Betül
Published: March 2024

Molecular innovations within key metabolisms can have profound impacts on element cycling and ecological distribution. Yet, much of the molecular foundations of early evolved enzymes and metabolisms are unknown. Here, we bring one such mystery to relief by probing the birth and evolution of the G-subunit protein, an integral component of certain members of the nitrogenase family, the only enzymes capable of biological nitrogen fixation. The G-subunit is a Paleoproterozoic-age orphan protein that appears more than 1 billion years after the origin of nitrogenases. We show that the G-subunit arose with novel nitrogenase metal dependence and the ecological expansion of nitrogen-fixing microbes following the transition in environmental metal availabilities and atmospheric oxygenation that began ∼2.5 billion years ago. We identify molecular features that suggest early G-subunit proteins mediated cofactor or protein interactions required for novel metal dependency, priming ancient nitrogenases and their hosts to exploit these newly diversified geochemical environments. We further examined the degree of functional specialization in G-subunit evolution with extant and ancestral homologs using laboratory reconstruction experiments. Our results indicate that permanent recruitment of the orphan protein depended on the prior establishment of conserved molecular features and showcase how contingent evolutionary novelties might shape ecologically important microbial innovations.
Real-World Evaluation of Primary Versus Secondary Prevention of Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer
Authors: Phillips William J , Saad Fred , Leigh Jennifer , Jooya Alborz , Webber Colleen , Morgan Scott , MacRae Robert , Bourque Jean-Marc , Tanuseputro Peter , Ong Michael
Published: March 2024

Introduction

Anti-osteoclast treatment with denosumab or zoledronate is known to effectively reduce the need for radiotherapy to bone and other skeletal-related events (SREs) in patients with metastatic castration-resistant prostate cancer (mCRPC). In this study, we analyze primary versus secondary initiation of bone-targeting agents (BTAs) relative to first palliative bone radiotherapy in patients dying of mCRPC.

Methods

Provincial administrative databases from Ontario, Canada identified patients with prostate cancer (2007-2018, n = 98 646) who received continuous androgen deprivation therapy (n = 29 453), died of prostate cancer (2013-2018, n = 3864), and received life-prolonging therapy for mCRPC (n = 1850). Variables were collected looking back 3 years from death. Multivariable analysis explored the relationship between clinical variables and BTAs.

Results

Of the 58% (1066/1850) patients with mCRPC who received BTA, only 289 (25.4%) started BTA prior to first palliative bone radiotherapy as primary prevention. Eight hundred and forty-eight (74.6%) patients either never received BTA before death (n = 447) or started BTA only after first bone radiotherapy (n = 401). More patients received denosumab (n = 825, 77%) than zoledronic acid (n = 241, 23%). 51.2% (582/1137) of palliative bone radiotherapy was initiated in the last 12 months of life. Factors associated with the use of BTA included elevated alkaline phosphatase (OR = 1.0, P = .023), de novo metastases (OR = 1.4, P = .005), medical oncologist involvement (OR = 2.0, P = .007), diagnosis 2012-2017 versus 2007-2011 (OR = 0.75, P = .034), and academic center (OR = 0.061, P = .007).

Conclusion

A majority of patients with mCRPC never receive BTAs prior to first SRE, despite universal access and availability of these agents in Ontario. These results highlight an opportunity to improve outcomes by emphasizing early introduction of BTA in patients with mCRPC being started on systemic therapy.
‘A System Only to Be Defended on the Principle of Positive and Ascertained Necessity’: Quarantine and Thomas Maitland’s Contribution to the Medical Debates of 1819 and 1824
Authors: Zarokostas Evangelos (Aggelis)
Published: March 2024

This article focusses on the ‘plague debates’ which took place in the British parliament in 1819 and 1824, where the opinions of non-medical experts were also taken into account; particularly those of officials who had acquired relevant practical experience. Such opinions were crucial in politicising the medical debate from one of the nature of plagues, towards an evaluation of the impact of quarantine more broadly. Paying closer attention at the correspondence between the colonial governor of Malta and the Ionian Islands, and the colonial secretary, it reveals a different aspect of the contagion inquiry in Britain—one considering medical knowledge about plagues that was highly speculative. While most historical works illuminate the establishment of what was considered to be medical evidence, there is less work about the political, economic or even personal motives which underlined interventions in these debates.
Shifting Cohort Patterns in the Use of Drugs with Elevated Overdose Risk in the United States
Authors: England Kira , Luo Liying , Verdery Ashton M , Monnat Shannon M
Published: March 2024

Rising drug overdose rates are a major social problem, but understanding of trends in the use of high-risk drugs is limited. The increasingly addictive potential of high-risk drugs, broader social changes, and the importance of peers and social contexts in shaping use may create conditions in which some cohorts have elevated use further into adulthood than others. We use an age-period-cohort model that defines cohort effects as the differential influences of social events for individuals of different ages. We analyze data from the 1979–2018 National Survey on Drug Use and Health to study past-year (mis)use of prescription analgesics, heroin, cocaine, and methamphetamine. Pre-1990 cohorts had either consistently lower than average odds or decreasing odds of use as they aged. The 1990s cohorts had higher than average odds of use, which increased as they aged. Early-2000s cohorts had increasing odds of use with age, despite low odds in adolescence. High-risk drug use appears to be an important cohort differentiating mechanism, with implications for policy and theories of deviance and stratification. The typical focus on period trends obscures the elevated odds of high-risk drug use in certain cohorts, whose members are entering the ages when overdose is most likely and consequences become most pronounced.
Past and future of alveolar organoids for lung regenerative medicine
Authors: Mikawa Ryuta , Gotoh Shimpei
Published: March 2024

The lung is regarded as having limited regenerative capacity, and there are few treatment options for refractory lung diseases, such as interstitial pneumonia. Lung transplantation is the final option available in some scenarios. Research in this area has been slow owing to the complex structure of the lung for efficient gas exchange between the alveolar spaces and capillaries as well as the difficulty in obtaining specimens from patients with progressive lung disease. However, basic research over the past decade in the field of mouse and human embryology using genetic lineage tracing techniques and stem cell biology using primary and pluripotent stem cell-derived alveolar organoids has begun to clarify the tissue response in various intractable lung diseases and the mechanisms underlying remodeling. Advancement in this area may expand potential therapeutic targets for alveolar regeneration, providing alternatives to lung transplantation, and contribute to the development of effective therapeutic methods that activate or repopulate stem cells in the lung. In this review, we cover research focused on alveolar epithelial cells and discuss methods expected to regenerate lungs that are damaged by diseases.
Recapitulating familial hypercholesterolemia in a mouse model by knock‐in patient‐specific LDLR mutation
Authors: Liu Jing , Yang Fayu , Shang Lu , Cai Shuo , Wu Yuting , Liu Yingchun , Zhang Lifang , Fei Chenzhong , Wang Mi , Gu Feng
Published: March 2024

Familial hypercholesterolemia (FH) is one of the most prevalent monogenetic disorders leading to cardiovascular disease (CVD) worldwide. Mutations in Ldlr, encoding a membrane‐spanning protein, account for the majority of FH cases. No effective and safe clinical treatments are available for FH. Adenine base editor (ABE)‐mediated molecular therapy is a promising therapeutic strategy to treat genetic diseases caused by point mutations, with evidence of successful treatment in mouse disease models. However, due to the differences in the genomes between mice and humans, ABE with specific sgRNA, a key gene correction component, cannot be directly used to treat FH patients. Thus, we generated a knock‐in mouse model harboring the partial patient‐specific fragment and including the Ldlr W490X mutation. LdlrW490X/W490X mice recapitulated cholesterol metabolic disorder and clinical manifestations of atherosclerosis associated with FH patients, including high plasma low‐density lipoprotein cholesterol levels and lipid deposition in aortic vessels. Additionally, we showed that the mutant Ldlr gene could be repaired using ABE with the cellular model. Taken together, these results pave the way for ABE‐mediated molecular therapy for FH.
The ecotin‐like peptidase inhibitor of Trypanosoma cruzi prevents TMPRSS2‐PAR2‐TLR4 crosstalk downmodulating infection and inflammation
Authors: Costa Tatiana F. R. , Catta‐Preta Carolina M. C. , Goundry Amy , Carvalho Danielle B. , Rodrigues Nathalia S. , Vivarini Aislan C. , de Abreu Mayra Fonseca , Reis Flavia C. G. , Lima Ana Paula C. A.
Published: March 2024

Trypanosoma cruzi is the causative agent of Chagas disease, a chronic pathology that affects the heart and/or digestive system. This parasite invades and multiplies in virtually all nucleated cells, using a variety of host cell receptors for infection. T. cruzi has a gene that encodes an ecotin‐like inhibitor of serine peptidases, ISP2. We generated ISP2‐null mutants (Δisp2) in T. cruzi Dm28c using CRISPR/Cas9. Epimastigotes of Δisp2 grew normally in vitro but were more susceptible to lysis by human serum compared to parental and ISP2 add‐back lines. Tissue culture trypomastigotes of Δisp2 were more infective to human muscle cells in vitro, which was reverted by the serine peptidase inhibitors aprotinin and camostat, suggesting that host cell epitheliasin/TMPRSS2 is the target of ISP2. Pretreatment of host cells with an antagonist to the protease‐activated receptor 2 (PAR2) or an inhibitor of Toll‐like receptor 4 (TLR4) selectively counteracted the increased cell invasion by Δisp2, but did not affect invasion by parental and add‐back lines. The same was observed following targeted gene silencing of PAR2, TLR4 or TMPRSS2 in host cells by siRNA. Furthermore, Δisp2 caused increased tissue edema in a BALB/c mouse footpad infection model after 3 h differently to that observed following infection with parental and add‐back lines. We propose that ISP2 contributes to protect T. cruzi from the anti‐microbial effects of human serum and to prevent triggering of PAR2 and TLR4 in host cells, resulting in the modulation of host cell invasion and contributing to decrease inflammation during acute infection.
Complete remission with histamine blocker in a patient with intractable hyperadrenergic postural orthostatic tachycardia syndrome secondary to long coronavirus disease syndrome
Authors: González-Alvarez Felipe , Estañol Bruno , González-Hermosillo Jesús Antonio , Gómez-Pérez Francisco Javier , Tamez-Torres Karla Maria , Peña Eduardo , Cantú Carlos , Chiquete Erwin , Sifuentes-Osornio José , Alba-Lorenzo Maria del Carmen , Celestino-Montelongo Dulce Andrea , Salazar-Calderón Guadalupe E. , Aceves Buendia Jose de Jesus
Published: March 2024

The COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has emerged as a global public health concern and its sequels have barely started to outcrop. A good percentage of patients who suffered from COVID-19 are prone to develop long-COVID or post-COVID condition (PCC), a multisystemic, heterogeneous, chronic disorder. Patients with PCC may experience diverse manifestations, of which cardiovascular and neurological symptoms are among the most frequently reported. Indeed, dysautonomia presented as orthostatic intolerance has gained room following recent reports linking postural orthostatic tachycardia syndrome (POTS) with PCC. Disturbances in heart rate (HR) and blood pressure (BP) during postural changes are the cornerstones of orthostatic intolerance seen in patients suffering from PCC. A subtype of POTS, hyperadrenergic POTS, has been widely studied because of its association with mast cell activation syndrome (MCAS). Although a causative relationship between PCC, hyperadrenergic POTS, and MCAS remains unrevealed, these syndromes can overlap. We want to propose here a correlation produced by a close-loop mechanism with positive feedback established after SARS-CoV-2 infection in a previously healthy young patient.
Blood volume phenotypes and patient sex in resistant hypertension
Authors: Carry Brendan J. , Miller Wayne L.
Published: March 2024

The relationship of blood volume (BV) to systemic blood pressure (BP) is not well defined in resistant hypertension (RH). The goal of this study was to examine the extent to which systemic BP stratified by patient sex would impact BV phenotypes. A retrospective analysis of clinical and quantitative BV data was undertaken in a cohort of ambulatory patients with a history of controlled and uncontrolled RH. We analyzed 253 unique BVs with 54% of patients above goal BP of <150 mmHg. BV phenotypes were highly variable but no correlation of systolic BP to absolute BV or percentage deviation from normal volume was identified in either sex. Males demonstrated overall larger absolute BVs with higher prevalence of large plasma volume (PV) expansion; females were overall more hypovolemic by total BV but with a higher frequency of normal PV than males. Females trended towards more RBC mass deficit (true anemia) (49% vs. 38%. P = 0.084) while more males demonstrated RBC mass excess (erythrocythemia) (21% vs. 11%, P = 0.029). Importantly, a significant portion (52%) of patients with true anemia identified by BVA would go undetected by hemoglobin measurement alone. BV phenotypes are highly diverse in patients with RH. However, absolute BV or variability in BV phenotypes even when stratified by patient sex did not demonstrate an association with systemic BP. BV phenotyping provides a key to optimizing clinical management by identifying RBC mass profiles particularly distinguishing true anemia, dilutional anemia, and erythrocythemia and the contribution of PV expansion. Findings support the clinical utility of BV phenotyping in RH.