Stomata Are Driving the Direction of CO2-Induced Water-Use Efficiency Gain in Selected Tropical Trees in Fiji.

Understanding plant physiological response to a rising atmospheric CO2 concentration (ca) is key in predicting Earth system plant-climate feedbacks; however, the effects of long-term rising ca on plant gas-exchange characteristics in the tropics are largely unknown. Studying this long-term trend using herbarium records is challenging due to specimen trait variation. We assessed the impact of a ca rise of ~95 ppm (1927-2015) on the intrinsic water-use efficiency (iWUE) and maximum stomatal conductance (gsmax) of five tropical tree species in Fiji using the isotopic composition and stomatal traits of herbarium leaves. Empirical results were compared with simulated values using models that uniquely incorporated the variation in the empirical gsmax responses and species-specific parameterisation. The magnitude of the empirical iWUE and gsmax response was species-specific, ranging from strong to negligible. Stomatal density was more influential than the pore size in determining the gsmax response to ca. While our simulation results indicated that photosynthesis is the main factor contributing to the iWUE gain, stomata were driving the iWUE trend across the tree species. Generally, a stronger increase in the iWUE was accompanied by a stronger decline in stomatal response. This study demonstrates that the incorporation of variation in the gsmax in simulations is necessary for assessing an individual species' iWUE response to changing ca.

Correction: Performance of ferrite nanoparticles in inductive heating swing adsorption (IHSA): how tailoring material properties can circumvent the design limitations of a system.

Correction for 'Performance of ferrite nanoparticles in inductive heating swing adsorption (IHSA): how tailoring material properties can circumvent the design limitations of a system' by Maxim De Belder et al., Mater. Horiz., 2024, 11, 4144-4149, https://doi.org/10.1039/d4mh00377b.

The diagnostic potential of urine in paediatric patients undergoing initial treatment for tuberculous meningitis.

Tuberculous meningitis (TBM)-the extrapulmonary form of tuberculosis, is the most severe complication associated with tuberculosis, particularly in infants and children. The gold standard for the diagnosis of TBM requires cerebrospinal fluid (CSF) through lumbar puncture-an invasive sample collection method, and currently available CSF assays are often not sufficient for a definitive TBM diagnosis. Urine is metabolite-rich and relatively unexplored in terms of its potential to diagnose neuroinfectious diseases. We used an untargeted proton magnetic resonance (1H-NMR) metabolomics approach to compare the urine from 32 patients with TBM (stratified into stages 1, 2 and 3) against that from 39 controls in a South African paediatric cohort. Significant spectral bins had to satisfy three of our four strict cut-off quantitative statistical criteria. Five significant biological metabolites were identified-1-methylnicotinamide, 3-hydroxyisovaleric acid, 5-aminolevulinic acid, N-acetylglutamine and methanol-which had no correlation with medication metabolites. ROC analysis revealed that methanol lacked diagnostic sensitivity, but the other four metabolites showed good diagnostic potential. Furthermore, we compared mild (stage 1) TBM and severe (stages 2 and 3) TBM, and our multivariate metabolic model could successfully classify severe but not mild TBM. Our results show that urine can potentially be used to diagnose severe TBM.

Venous Thromboembolism in Patients with Glioblastoma: Molecular Mechanisms and Clinical Implications.

Patients with glioblastoma are among the cancer patients with the highest risk of developing venous thromboembolism (VTE). Long-term thromboprophylaxis is not generally prescribed because of the increased susceptibility of glioblastoma patients to intracranial hemorrhage. This review provides an overview of the current clinical standard for glioblastoma patients, as well as the molecular and genetic background which underlies the high incidence of VTE. The two main procoagulant proteins involved in glioblastoma-related VTE, podoplanin and tissue factor, are described, in addition to the genetic aberrations that can be linked to a hypercoagulable state in glioblastoma. Furthermore, possible novel biomarkers and future treatment strategies are discussed, along with the potential of sequencing approaches toward personalized risk prediction for VTE. A glioblastoma-specific VTE risk stratification model may help identifying those patients in which the increased risk of bleeding due to extended anticoagulation is outweighed by the decreased risk of VTE.

Multiplex spatial omics reveals changes in immune-epithelial crosstalk during inflammation and dysplasia development in chronic IBD patients.

Patients with long-standing inflammatory bowel disease (IBD) face an increased risk of developing colitis-associated cancer (CAC). Although IBD-induced prolonged inflammation seems to be involved in CAC pathogenesis, the specific molecular changes that contribute remain unknown. Here, we applied digital spatial RNA profiling, RNAscope, and imaging mass cytometry to examine paired uninflamed, inflamed, and early dysplastic mucosa of patients with IBD. We observed robust type 3 (IL-17) responses during inflammation, accompanied by elevated JAK-STAT signaling and phosphorylated STAT3 (P-STAT3) levels, with both inflamed and dysplastic mucosa displaying immune cell activation. Higher stromal P-STAT3 was detected in uninflamed and inflamed mucosa of patients who eventually developed dysplasia. CD8a+ T cells did not infiltrate inflamed or dysplastic epithelial regions in these patients, while control patients showed elevated CD8a in inflamed mucosa. Our study reveals distinct inflammatory patterns throughout CAC development, marked by an activated IL-17 pathway, engaged STAT3, and diminished cytotoxic T cell infiltration.

Case report: Comprehensive follow-up of a Colombian family carrying a novel MEN1 variant linked to a rare ACTH-producing pancreatic neuroendocrine carcinoma.

Background: Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder marked by pathogenic variants in the MEN1 tumor suppressor gene, leading to tumors in the parathyroid glands, pancreas, and pituitary. The occurrence of ACTH-producing pancreatic neuroendocrine carcinoma is exceedingly rare in MEN1. Case presentation: This report details a Colombian family harboring a novel MEN1 variant identified through genetic screening initiated by the index case. Affected family members exhibited primary hyperparathyroidism (PHPT) symptoms from their 20s to 50s. Uniquely, the index case developed an ACTH-secreting pancreatic neuroendocrine carcinoma, a rarity in MEN1 syndromes. Proactive screening enabled the early detection of pituitary neuroendocrine tumors (PitNETs) as microadenomas in two carriers, with subsequent surgical or pharmacological intervention based on the clinical presentation. Conclusion: Our findings underscore the significance of cascade screening in facilitating the early diagnosis and individualized treatment of MEN1, contributing to better patient outcomes. Additionally, this study brings to light a novel presentation of ACTH-producing pancreatic neuroendocrine carcinoma within the MEN1 spectrum, expanding our understanding of the disease's manifestations.

Comparison of Cardiopulmonary Exercise Test Variables to Predict Adverse Events in Patients with Heart Failure.

PURPOSE: Given the rising burden of heart failure (HF), stratification of patients at increased risk for adverse events is critical. We aim to compare the predictive value of various maximal and submaximal cardiopulmonary exercise test (CPET) variables for adverse events in patients with HF. METHODS: 237 patients with HF (66 [58-73] years, 30% women, 70% HF with reduced ejection fraction) completed a CPET and had five years of follow-up. Baseline characteristics and clinical outcomes (all-cause mortality, major adverse cardiovascular events, and cardiovascular-related hospitalization) were extracted from electronic patient files. Receiver operating characteristics curves for maximal (e.g. peak VO2) and submaximal CPET variables (e.g. VE/VCO2 slope, cardiorespiratory optimal point (COP), VO2 at anaerobic threshold) were compared using the Akaike Information Criterion (AIC) method, whereas their calibration was assessed. RESULTS: 103 participants (43%) reached the composite endpoint, and 55 (23%) died. Percent predicted peak VO2 was the best predictor for adverse outcomes (AIC: 302.6) followed by COP (AIC: 304.3), and relative peak VO2 (mL/(kg·min), AIC: 304.4). Relative peak VO2 (AIC: 217.1) and COP (AIC: 224.4) were also among the three best predictors for mortality, together with absolute peak VO2 (ml/min, AIC: 220.5). A good calibration between observed and predicted event rate was observed for these variables. CONCLUSIONS: Percent predicated and relative peak VO2 had the best predictive accuracy for adverse events and mortality, but the submaximal COP had a non-inferior predictive accuracy for adverse events in patients with HF. These findings highlight the potential of submaximal exercise testing in patients with HF.

Harnessing Nuclear Magnetic Resonance Spectroscopy to Decipher Structure and Dynamics of Clathrate Hydrates in Confinement: A Perspective.

This perspective outlines recent developments in the field of NMR spectroscopy, enabling new opportunities for in situ studies on bulk and confined clathrate hydrates. These hydrates are crystalline ice-like materials, built up from hydrogen-bonded water molecules, forming cages occluding non-polar gaseous guest molecules, including CH4, CO2 and even H2 and He gas. In nature, they are found in low-temperature and high-pressure conditions. Synthetic confined versions hold immense potential for energy storage and transportation, as well as for carbon capture and storage. Using previous studies, this report highlights static and magic angle spinning NMR hardware and strategies enabling the study of clathrate hydrate formation in situ, in bulk and in nano-confinement. The information obtained from such studies includes phase identification, dynamics, gas exchange processes, mechanistic studies and the molecular-level elucidation of the interactions between water, guest molecules and confining interfaces.

Morphological and Molecular Analysis of Two Mycophagous Nematodes, Aphelenchoides bicaudatus and A. rutgersi (Nematoda: Aphelenchoididae) from Florida Strawberry.

From 2016 to 2021, nematode surveys in Florida strawberry fields revealed several species of foliar nematodes (Aphelenchoides spp.). Aphelenchoides besseyi sensu stricto was detected only in 2016 and 2017 on photosynthetic strawberry leaves/buds, but other not well characterized populations of Aphelenchoides sp. were found on declining/dessicated leaves. Morphological analyses showed that these samples of Aphelenchoides sp. consisted of A. bicaudatus, a species detected in Florida for the first time, and A. rutgersi, a species previously reported in Florida from the citrus rhizosphere. These two species differed from A. besseyi in the shape of their tail terminus: bifurcate in A. bicaudatus; mucronate with a ventral thin mucro in A. rutgersi; and stellate in A. besseyi. One population each of these species was used for morphological and molecular analyses after being reared on Monilinia fructicola. Body and tail length differences were observed among Florida A. bicaudatus and other populations from the Far East and South Africa. Phylogenetic analyses of the rRNA gene sequences showed that Florida A. bicaudatus grouped with those of species from South Korea, Taiwan, and the Netherlands and several other populations listed as Aphelenchoides sp. from Brazil, Costa Rica, and Japan, which were considered as representatives of A. bicaudatus in this study. Similarly, sequences of Florida A. rutgersi grouped with those from environmental samples in Japan and North Carolina, which were listed as Aphelenchoides sp. and were considered as representatives of A. rutgersi in this study. Photosynthetic strawberry leaf samples were free from both A. bicaudatus and A. rutgersi, indicating that these two species did not damage strawberry. They were associated with desiccated leaves and/or propagative stolons, usually infected by fungi, confirming that they are mycetophagous under field conditions in this study. Results of soybean leaf inoculation on moist filter paper containing A. bicaudatus specimens showed that this species could become phytophagous under artificial conditions. Nematodes penetrated the leaf epidermis and migrated into the mesophyll causing leaf tissue discoloration/necrosis, which remained localized within the infested area. Soybean leaf damage was almost negligible, and no nematode reproduction was observed in the inoculated soybean areas.

Socio-economic and environmental trade-offs in Amazonian protected areas and Indigenous territories revealed by assessing competing land uses.

Protected area (PA) assessments rarely evaluate socio-economic and environmental impacts relative to competing land uses, limiting understanding of socio-environmental trade-offs from efforts to protect 30% of the globe by 2030. Here we assess deforestation and poverty outcomes (fiscal income, income inequality, sanitation and literacy) between 2000 and 2010 of strict PAs (SPAs), sustainable-use PAs (SUPAs) and Indigenous territories (ITs) compared with different land uses (agriculture and mining concessions) across ~5,500 census tracts in the Brazilian Legal Amazon. ITs reduced deforestation relative to all alternative land uses (48-83%) but had smaller socio-economic benefits compared with other protection types and land uses (18-36% depending on outcome), indicating that Indigenous communities experience socio-economic trade-offs. By contrast, SUPAs, and potentially SPAs, did not reduce deforestation relative to small-scale agriculture (landholdings <10 ha) but did so relative to larger agricultural landholdings (70-82%). Critically, these reductions in deforestation frequently occurred without negative socio-economic outcomes. By contrast, ITs and SUPAs protected against deforestation from mining, but at the cost of smaller improvements in income and inequality. Our results suggest that although PAs in the Brazilian Legal Amazon substantially reduced deforestation without compromising local socio-economic development, efforts to secure Indigenous rights need additional interventions to ensure these communities are not further disadvantaged.

Patient-reported outcomes in neuro-oncology.

PURPOSE OF REVIEW: To provide up-to-date evidence on patient-reported outcomes (PROs) in neuro-oncology, with a focus on the core constructs of health-related quality of life (HRQoL) and the use of PROs in clinical trials and clinical practice.[Supplemental Digital Content: Video Abstract PROs in Neuro-Oncology.mov]. RECENT FINDINGS: PROs are gaining importance in brain tumor research and medical care. For patients with a brain tumor, core PRO constructs are pain, difficulty communicating, perceived cognition, seizures, symptomatic adverse events, physical functioning and role and social functioning, which are assessed through patient-reported outcome measures (PROMs). Initiatives have been taken to improve the reliability and robustness of PRO data, including standardization of items included in clinical trial protocols (the SPIRIT-PRO extension) and formulation of PRO priority objectives for use in clinical trials (the SISAQOL-Innovative Medicines Initiative). In brain tumor patients with cognitive impairment, caregiver-reported outcomes may complement or replace PROs to increase accuracy. The next key challenge will be to widely implement PROs and apply PRO data in clinical practice to benefit patients with brain tumors. SUMMARY: PROs are clinically relevant endpoints providing information only known by the patient. Standardization of the use of PROs in clinical trials and wide implementation in clinical practice is needed to improve HRQoL of brain tumor patients.

Microbiota of pest insect Nezara viridula mediate detoxification and plant defense repression.

The Southern green shield bug, Nezara viridula, is an invasive piercing and sucking pest insect that feeds on crop plants and poses a threat to global food production. Given that insects are known to live in a close relationship with microorganisms, our study provides insights into the community composition and function of the N. viridula-associated microbiota and its effect on host-plant interactions. We discovered that N. viridula hosts both vertically and horizontally transmitted microbiota throughout different developmental stages and their salivary glands harbor a thriving microbial community that is transmitted to the plant while feeding. The N. viridula microbiota was shown to aid its host with the detoxification of a plant metabolite, namely 3-nitropropionic acid, and repression of host plant defenses. Our results demonstrate that the N. viridula-associated microbiota plays an important role in interactions between insects and plants and could therefore be considered a valuable target for the development of sustainable pest control strategies.

Accuracy of patient-specific I-131 dosimetry using hybrid whole-body planar-SPECT/CT I-123 and I-131 imaging.

PURPOSE: This study aimed to assess the accuracy of patient-specific absorbed dose calculations for tumours and organs at risk in radiopharmaceutical therapy planning, utilizing hybrid planar-SPECT/CT imaging. METHODS: Three Monte Carlo (MC) simulated digital patient phantoms were created, with time-activity data for mIBG labelled to I-123 (LEHR and ME collimators) and I-131 (HE collimator). The study assessed the accuracy of the mean absorbed doses for I-131-mIBG therapy treatment planning. Multiple planar whole-body (WB) images were simulated (between 1 to 72 h post-injection (p.i)). The geometric-mean image of the anterior and posterior WB images was calculated, with scatter and attenuation corrections applied. Time-activity curves were created for regions of interest over the liver and two tumours (diameters: 3.0 cm and 5.0 cm) in the WB images. A corresponding SPECT study was simulated at 24 h p.i and reconstructed using the OS-EM algorithm, incorporating scatter, attenuation, collimator-detector response, septal scatter and penetration corrections. MC voxel-based absorbed dose rate calculations used two image sets, (i) the activity distribution represented by the SPECT images and (ii) the activity distribution from the SPECT images distributed uniformly within the volume of interest. Mean absorbed doses were calculated considering photon and charged particle emissions, and beta emissions only. True absorbed doses were calculated by MC voxel-based dosimetry of the known activity distributions for reference. RESULTS: Considering photon and charged particle emissions, mean absorbed dose accuracies across all three radionuclide-collimator combinations of 3.8 ± 5.5% and 0.1 ± 0.9% (liver), 5.2 ± 10.0% and 4.3 ± 1.7% (3.0 cm tumour) and 15.0 ± 5.8% and 2.6 ± 0.6% (5.0 cm tumour) were obtained for image set (i) and (ii) respectively. Considering charged particle emissions, accuracies of 2.7 ± 4.1% and 5.7 ± 0.7% (liver), 3.2 ± 10.2% and 9.1 ± 1.7% (3.0 cm tumour) and 13.6 ± 5.7% and 7.0 ± 0.6% (5.0 cm tumour) were obtained for image set (i) and (ii) respectively. CONCLUSION: The hybrid WB planar-SPECT/CT method proved accurate for I-131-mIBG dosimetry, suggesting its potential for personalized treatment planning.

Performance of ferrite nanoparticles in inductive heating swing adsorption (IHSA): how tailoring material properties can circumvent the design limitations of a system.

Inductive heating swing adsorption (IHSA) using hybrid adsorbents incorporating a porous material and ferrite nanoparticles holds promise to be a performant, electrified alternative for conventional gas separation. Successful implementation of hybrid adsorbents in IHSA depends on achieving a maximal specific absorption rate (SAR) in the conditions and at the frequency of the induction setup. This paper outlines and demonstrates successful strategies for optimization of the particle composition, tailoring the coercivity and susceptibility of the ferrite particles to optimal performance in a given alternating magnetic field.

Identity verification of monoclonal antibodies by triple injection capillary zone electrophoresis.

This paper presents an approach based on triple injection capillary zone electrophoresis for identification of monoclonal antibodies. The analyte to be identified is injected between two zones of a known reference. The distances between the reference zones (plug I and III) and the target zone (plug II) are adjusted by partial electrophoresis of the first and second injection plugs. The full migration time of the target analyte is calculated from the observed migration time by considering the migration times of the reference in the first and third injection plugs. The relative migration time, that is, the ratio between the full migration time of the analyte and the migration time of the reference in the third injection plug provides the basis for identification. Here, eight monoclonal antibodies, including a pair of biosimilars, were used interchangeably as both analyte and reference to investigate potential of the method. The relative migration time for a preliminary positive identification were found to vary between 0.994 and 1.006 (1.000 ± 0.006, p = 95%). Beside the relative migration time, isoform distribution, peak profiles, and early migrating peaks, originating from components in the pharmaceutical formulations, were successfully used to verify the identity of all tested monoclonal antibodies.

The role of imaging in focal neuropathies.

Electrodiagnostic testing (EDX) has been the diagnostic tool of choice in peripheral nerve disease for many years, but in recent years, peripheral nerve imaging has been used ever more frequently in daily clinical practice. Nerve ultrasound and magnetic resonance (MR) neurography are able to visualize nerve structures reliably. These techniques can aid in localizing nerve pathology and can reveal significant anatomical abnormalities underlying nerve pathology that may have been otherwise undetected by EDX. As such, nerve ultrasound and MR neurography can significantly improve diagnostic accuracy and can have a significant effect on treatment strategy. In this chapter, the basic principles and recent developments of these techniques will be discussed, as well as their potential application in several types of peripheral nerve disease, such as carpal tunnel syndrome (CTS), ulnar neuropathy at the elbow (UNE), radial neuropathy, brachial and lumbosacral plexopathy, neuralgic amyotrophy (NA), fibular, tibial, sciatic, femoral neuropathy, meralgia paresthetica, peripheral nerve trauma, tumors, and inflammatory neuropathies.

A 3D organoid platform that supports liver-stage P.falciparum infection can be used to identify intrahepatic antimalarial drugs.

Malaria, a major public health burden, is caused by Plasmodium spp parasites that first replicate in the human liver to establish infection before spreading to erythrocytes. Liver-stage malaria research has remained challenging due to the lack of a clinically relevant and scalable in vitro model of the human liver. Here, we demonstrate that organoids derived from intrahepatic ductal cells differentiated into a hepatocyte-like fate can support the infection and intrahepatic maturation of Plasmodium falciparum. The P.falciparum exoerythrocytic forms observed expressed both early and late-stage parasitic proteins and decreased in frequency in response to treatment with both known and putative antimalarial drugs that target intrahepatic P.falciparum. The P.falciparum-infected human liver organoids thus provide a platform not only for fundamental studies that characterise intrahepatic parasite-host interaction but can also serve as a powerful translational tool in pre-erythrocytic vaccine development and to identify new antimalarial drugs that target the liver stage infection.

A strategy for differential abundance analysis of sparse microbiome data with group-wise structured zeros.

Comparing the abundance of microbial communities between different groups or obtained under different experimental conditions using count sequence data is a challenging task due to various issues such as inflated zero counts, overdispersion, and non-normality. Several methods and procedures based on counts, their transformation and compositionality have been proposed in the literature to detect differentially abundant species in datasets containing hundreds to thousands of microbial species. Despite efforts to address the large numbers of zeros present in microbiome datasets, even after careful data preprocessing, the performance of existing methods is impaired by the presence of inflated zero counts and group-wise structured zeros (i.e. all zero counts in a group). We propose and validate using extensive simulations an approach combining two differential abundance testing methods, namely DESeq2-ZINBWaVE and DESeq2, to address the issues of zero-inflation and group-wise structured zeros, respectively. This combined approach was subsequently successfully applied to two plant microbiome datasets that revealed a number of taxa as interesting candidates for further experimental validation.