Spatial and seasonal variation in disinfection byproducts concentrations in a rural public drinking water system: A case study of Martin County, Kentucky, USA.

To increase our understanding of the factors that influence formation of disinfection byproducts (DBPs) in rural drinking systems, we investigated the spatial and seasonal variation in trihalomethane (THM) and haloacetic acid (HAA) concentrations in relation to various chemical and physical variables in a rural public drinking water system in Martin County, Kentucky, USA. We collected drinking water samples from 97 individual homes over the course of one year and analyzed them for temperature, electrical conductivity, pH, free chlorine, total chlorine, THMs (chloroform, bromodichloromethane, dibromochloromethane, dichlorobromomethane, and bromoform) and HAAs (monochloroacetic acid, dichloroacetic acid, trichloroacetic acid, bromoacetic acid, and dibromoacetic acid). Spatial autocorrelation analysis showed only weak overall clustering for HAA concentrations and none for THMs. The relationship between modeled water age and TTHM or HAA5 concentrations varied seasonally. In contrast, there was strong variation for both HAA and THMs, with concentrations of HAA peaking in mid-summer and THMs peaking in early fall. Multiple regression analysis revealed that THM concentrations were strongly correlated with conductivity, while HAA concentrations were more strongly correlated with water temperature. Individual DBP species that only contained chlorine halogen groups were strongly correlated with temperature, while compounds containing bromine were more strongly correlated with conductivity. Further investigation revealed that increased drinking water conductivity associated with low discharge of the Tug Fork River, the source water, is highly correlated with increased concentrations of bromide. Discharge and conductivity of the Tug Fork River changed dramatically through the year contributing to a seasonal peak in bromide concentrations in the late summer and early fall and appeared to be a driver of brominated THM concentrations. Brominated DBPs tend to have higher toxicity than DBPs containing only chlorine, therefore this study provides important insight into the seasonal factors driving risk from exposure to DBPs in rural drinking water systems impacted by bromide.

Using viral diversity to identify HIV-1 variants under HLA-dependent selection in a systematic viral genome-wide screen.

The pathogenesis of HIV-1 infection is governed by a highly dynamic, time-dependent interaction between the host and the viral genome. In this study, we developed a novel systematic approach to assess the host-virus interaction, using average pairwise viral diversity as a proxy for time since infection, and applied this method to nearly whole viral genome sequences (n = 4,464), human leukocyte antigen (HLA) genotyping data (n = 1,044), and viral RNA load (VL) measurements during the untreated chronic phase (n = 829) of Swiss HIV Cohort Study participants. Our systematic genome-wide screen revealed for 98 HLA/viral-variant pairs a signature of immune-driven selection in the form of an HLA-dependent effect of infection time on the presence of HIV amino acid variants. Of these pairs, 12 were found to have an effect on VL. Furthermore, 28/58 pairs were validated by time-to-event analyses and 48/92 by computational HLA-epitope predictions. Our diversity-based approach allows a powerful and systematic investigation of the interaction between the virus and cellular immunity, revealing a notable subset of such interaction effects. From an evolutionary perspective, these observations underscore the complexity of HLA-mediated selection pressures on the virus that shape viral evolution and pathogenesis.

Evaluation of coronary microvascular dysfunction using magnetocardiography: A new application to an old technology.

Background: In patients with angina and non-obstructive coronary artery disease (ANOCA), diagnosis of coronary microvascular dysfunction (CMD) remains an unmet need. Magnetocardiography (MCG), is a rest-based, non-invasive scan that can detect weak electrophysiological changes that occur at the early phase of ischemia. Objective: This study assessed the ability of MCG to detect CMD in ANOCA patients as compared to reference standard, invasive coronary flow reserve (CFR). Methods: Patients with ANOCA and invasive coronary physiologic assessment using intracoronary flow measurements with Doppler and thermodilution methods were enrolled. CMD was defined dichotomously as an invasive CFR < 2.0 by Doppler or thermodilution assessment. Noninvasive 36-channel 90-s MCG scan was performed and quantitative assessment of four distinct MCG features was completed. We evaluated the diagnostic performance of 2 or more abnormal MCG features to detect CMD in the overall cohort and performed a subgroup analysis in the subset of patients with Doppler CFR assessment. Results: Among 79 ANOCA patients, 25 were CMD positive and 54 patients were CMD negative by CFR. Using invasive CFR as reference, MCG had an ROC AUC of 0.66 with a sensitivity of 68 % and specificity of 65 % for the detection of CMD. In the subgroup with Doppler CFR assessment, MCG had an ROC AUC of 0.76 with a sensitivity of 75 % and specificity of 77 %. Conclusions: In ANOCA patients, MCG demonstrates the ability to detect CMD using a 90-second non-invasive scan without the need for an intravenous stressor or ionizing radiation. Further investigations are needed to validate an MCG-based diagnostic pathway for CMD.

Benefits and limits of biological nitrification inhibitors for plant nitrogen uptake and the environment.

Plant growth and high yields are secured by intensive use of nitrogen (N) fertilizer, which, however, pollutes the environment, especially when N is in the form of nitrate. Ammonium is oxidized to nitrate by nitrifiers, but roots can release biological nitrification inhibitors (BNIs). Under what conditions does root-exudation of BNIs facilitate nitrogen N uptake and reduce pollution by N loss to the environment? We modeled the spatial-temporal dynamics of nitrifiers, ammonium, nitrate, and BNIs around a root and simulated root N uptake and net rhizosphere N loss over the plant's life cycle. We determined the sensitivity of N uptake and loss to variations in the parameter values, testing a broad range of soil-plant-microbial conditions, including concentrations, diffusion, sorption, nitrification, population growth, and uptake kinetics. An increase in BNI exudation reduces net N loss and, under most conditions, increases plant N uptake. BNIs decrease uptake in the case of (1) low ammonium concentrations, (2) high ammonium adsorption to the soil, (3) rapid nitrate- or slow ammonium uptake by the plant, and (4) a slowly growing or (5) fast-declining nitrifier population. Bactericidal inhibitors facilitate uptake more than bacteriostatic ones. Some nitrification, however, is necessary to maximize uptake by both ammonium and nitrate transporter systems. An increase in BNI exudation should be co-selected with improved ammonium uptake. BNIs can reduce N uptake, which may explain why not all species exude BNIs but have a generally positive effect on the environment by increasing rhizosphere N retention.

Analyzing water hyacinth plants from two South African rivers for the detection of seven pharmaceuticals and their metabolites.

Water hyacinth plants (Eichhornia crassipes Mart.) collected from two South African rivers were analyzed in order to investigate their suitability for judging the presence of pharmaceuticals in the water. Thereby, a number of drugs, including amitriptyline, atenolol, citalopram, orphenadrine, lidocaine, telmisartan, and tramadol, could be detected. Particularly for the latter substance, relatively high concentrations (more than 5000 ng g-1 dry plant material) were detected in the water plants. Subsequently, the plant extracts were also screened for drug-derived transformation products, whereby a series of phase-one metabolites could be tentatively identified.

An Overview of Tsetse Fly Repellents: Identification and Applications.

Tsetse flies are vectors of the parasite trypanosoma that cause the neglected tropical diseases human and animal African trypanosomosis. Semiochemicals play important roles in the biology and ecology of tsetse flies. Previous reviews have focused on olfactory-based attractants of tsetse flies. Here, we present an overview of the identification of repellents and their development into control tools for tsetse flies. Both natural and synthetic repellents have been successfully tested in laboratory and field assays against specific tsetse fly species. Thus, these repellents presented as innovative mobile tools offer opportunities for their use in integrated disease management strategies.

A novel adapted MRI-based scheme for Dejour classification of trochlear dysplasia.

PURPOSE: To elaborate an optimized scheme for the Dejour classification of trochlear dysplasia based on axial and sagittal MR images and to evaluate its intra- and inter-reader reliability. MATERIAL AND METHODS: Over a period of 20 months patients with a knee MRI and the diagnosis of trochlear dysplasia were retrospectively included. Exclusion criteria were incomplete examination, qualitatively non-diagnostic examination, post trochlear surgery, missing informed consent for research purposes. Three independent evaluations were performed by two radiologists: first using an established description of the Dejour classification (types A-D) and then two evaluations using a new adapted scheme (types A-D). The adapted scheme includes a shallow trochlea, in type A no spur/no cliff, in type B with spur/no cliff, in type C no spur/with cliff, and in type D with spur/with cliff. RESULTS: One hundred seventy-one knee MRIs (female:65.5%; left side:52.6%) were included with a median age of 34.3 years (range:11.3-79.2). Inter-reader reliability using the established description was fair for the four-type-classification (kappa(k) = 0.23; 95%CI:0.11-0.34), fair for differentiation low-grade versus high-grade dysplasia (k = 0.28;0.13-0.43), slight for differentiation spur versus no-spur types (k = 0.20;0.05-0.34). Inter-reader reliability using the adapted scheme was substantial (k = 0.79;0.75-0.83) for the four-type-classification, substantial for differentiation low-grade versus high-grade dysplasia (k = 0.80;0.75-0.85), substantial for differentiation spur versus no-spur presence (k = 0.76;0.71-0.81). Intra-reader reliability was almost perfect for the adapted scheme (k-values: 0.88-0.95; 95%CIs: 0.84-0.98). CONCLUSION: The novel adapted scheme for Dejour classification shows an almost perfect intra-reader reliability and a substantially higher inter-reader reliability. It may become a helpful tool in the daily diagnostic work of radiologists.

Localization of protoporphyrin IX during glioma-resection surgery via paired stimulated Raman histology and fluorescence microscopy.

The most widely used fluorophore in glioma-resection surgery, 5-aminolevulinic acid (5-ALA), is thought to cause the selective accumulation of fluorescent protoporphyrin IX (PpIX) in tumour cells. Here we show that the clinical detection of PpIX can be improved via a microscope that performs paired stimulated Raman histology and two-photon excitation fluorescence microscopy (TPEF). We validated the technique in fresh tumour specimens from 115 patients with high-grade gliomas across four medical institutions. We found a weak negative correlation between tissue cellularity and the fluorescence intensity of PpIX across all imaged specimens. Semi-supervised clustering of the TPEF images revealed five distinct patterns of PpIX fluorescence, and spatial transcriptomic analyses of the imaged tissue showed that myeloid cells predominate in areas where PpIX accumulates in the intracellular space. Further analysis of external spatially resolved metabolomics, transcriptomics and RNA-sequencing datasets from glioblastoma specimens confirmed that myeloid cells preferentially accumulate and metabolize PpIX. Our findings question 5-ALA-induced fluorescence in glioma cells and show how 5-ALA and TPEF imaging can provide a window into the immune microenvironment of gliomas.

Soft confinement of water in aliphatic alcohols: MIR/NIR spectroscopic and DFT studies.

Here, we present the first examination of the state of water under a soft confinement in eight aliphatic alcohols including cyclopentanol, 1-pentanol, 1-hexanol, 1-heptanol, 1-octanol, 1-decanol, 2-octanol and 3-octanol. Due to relatively large size of the aliphatic part, water has limited solubility in all studied alcohols. Water content in saturated solutions was determined by Karl Fischer titration and correlated with the spectroscopic data. This way, we determined the molar absorptivity of the ν2+ν3 combination mode. The effect of addition of water and temperature variation was monitored by ATR-IR and NIR spectroscopy. Analysis of the experimental results was guided by DFT calculations, which provided the structures, harmonic MIR spectra and binding energies of selected alcohol-water complexes. Our studies demonstrated that the state of water in alcohols is related to its solubility, which depends on structure of solvent molecules. The solubility of water in 1-alcohols decreases on increasing of the chain length, but for long chain alcohols this effect is less evident. More apparent solubility reduction appears in going from the primary to secondary alcohols. The effective shielding of the OH group in the linear alcohols is achieved when on both sides of the OH group are ethyl or longer substituents, while the shielding by methyl groups is less efficient. Water is much better soluble in the cyclic alcohols as compared with the linear ones due to better accessibility of the OH group. The soft confinement of water in aliphatic alcohols allows for flexible structural arrangements and interactions. Even at low water content, we did not observe free molecules of water. At these conditions, the molecules of water are singly or doubly bonded to the OH groups from the alcohol. Increasing solubility of water reduces the number of the free OH groups and leads to formation of water clusters. Obtained results allow concluding that in alcohols with sizable aliphatic part the molecules of water are confined in the vicinity of the OH groups.

Loss of tolerance precedes triggering and lifelong persistence of pathogenic type I interferon autoantibodies.

Autoantibodies neutralizing type I interferons (IFN-Is) can underlie infection severity. Here, we trace the development of these autoantibodies at high-resolution using longitudinal samples from 1,876 well-treated individuals living with HIV over a 35-year period. Similar to general populations, ∼1.9% of individuals acquired anti-IFN-I autoantibodies as they aged (median onset ∼63 years). Once detected, anti-IFN-I autoantibodies persisted lifelong, and titers increased over decades. Individuals developed distinct neutralizing and non-neutralizing autoantibody repertoires at discrete times that selectively targeted combinations of IFNα, IFNß, and IFNω. Emergence of neutralizing anti-IFNα autoantibodies correlated with reduced baseline IFN-stimulated gene levels and was associated with subsequent susceptibility to severe COVID-19 several years later. Retrospective measurements revealed enrichment of pre-existing autoreactivity against other autoantigens in individuals who later developed anti-IFN-I autoantibodies, and there was evidence for prior viral infections or increased IFN at the time of anti-IFN-I autoantibody triggering. These analyses suggest that age-related loss of self-tolerance prior to IFN-I immune-triggering poses a risk of developing lifelong functional IFN-I deficiency.

Radiolabeling and Preclinical Evaluation of Therapeutic Efficacy of 225Ac-ch806 in Glioblastoma and Colorectal Cancer Xenograft Models.

The epidermal growth factor receptor (EGFR) protein is highly expressed in a range of malignancies. Although therapeutic interventions directed toward EGFR have yielded therapeutic responses in cancer patients, side effects are common because of normal-tissue expression of wild-type EGFR. We developed a novel tumor-specific anti-EGFR chimeric antibody ch806 labeled with 225Ac and evaluated its in vitro properties and therapeutic efficacy in murine models of glioblastoma and colorectal cancer. Methods: 225Ac-ch806 was prepared using different chelators, yielding [225Ac]Ac-macropa-tzPEG3Sq-ch806 and [225Ac]Ac-DOTA-dhPzPEG4-ch806. Radiochemical yield, purity, apparent specific activity, and serum stability of 225Ac-ch806 were quantified. In vitro cell killing effect was examined. The biodistribution and therapeutic efficacy of 225Ac-ch806 were investigated in mice with U87MG.de2-7 and DiFi tumors. Pharmacodynamic analysis of tumors after therapy was performed, including DNA double-strand break immunofluorescence of γH2AX, as well as immunohistochemistry for proliferation, cell cycle arrest, and apoptosis. Results: [225Ac]Ac-macropa-tzPEG3Sq-ch806 surpassed [225Ac]Ac-DOTA-dhPzPEG4-ch806 in radiochemical yield, purity, apparent specific activity, and serum stability. [225Ac]Ac-macropa-tzPEG3Sq-ch806 was therefore used for both in vitro and in vivo studies. It displayed a significant, specific, and dose-dependent in vitro cell-killing effect in U87MG.de2-7 cells. 225Ac-ch806 also displayed high tumor uptake and minimal uptake in normal tissues. 225Ac-ch806 significantly inhibited tumor growth and prolonged survival in both U87MG.de2-7 and DiFi models. Enhanced γH2AX staining was observed in 225Ac-ch806-treated tumors compared with controls. Reduced Ki-67 expression was evident in all 225Ac-ch806-treated tumors. Increased expression of p21 and cleaved caspase 3 was shown in U87MG.de2-7 and DiFi tumors treated with 225Ac-ch806. Conclusion: In glioblastoma and colorectal tumor models, 225Ac-ch806 significantly inhibited tumor growth via induction of double-strand breaks, thereby constraining cancer cell proliferation while inducing cell cycle arrest and apoptosis. These findings underscore the potential clinical applicability of 225Ac-ch806 as a potential therapy for EGFR-expressing solid tumors.

Upgrading and Enhancement of Recycled Polyethylene Terephthalate with Chain Extenders: In-Depth Material Characterization.

Chemical chain extenders (CEs) can be used to restore the properties of recycled low-molecular-weight polyethylene terephthalate (PET). The aim of this work is to investigate the influence of the type and concentration of the CEs Joncryl and pyromellitic dianhydride (PMDA) on the viscosity and other rheological properties with a unique combination of different methods based on industrial samples originating from recycled PET bottles and trays. The resulting chain-extended thermoplastics were characterized by a combination of differential scanning calorimetry, viscometry, cone plate rheometry, pyrolysis-gas chromatography-mass spectroscopy, optical photothermal infrared spectroscopy, 13C solid-state- and 1H NMR liquid spectroscopy, and size exclusion chromatography. For a recycled PET mixture containing bottle and tray materials, our investigations have shown that a significantly better effect for chain elongation can be achieved with Joncryl compared to PMDA. This can presumably be attributed to water molecules formed during the use of PMDA, which accelerate the degradation of PET. The storage modulus values are therefore significantly higher for the samples with Joncryl compared to PMDA. The results of this study show that chain extension with Joncryl proceeds better compared to the reaction with PMDA.

Chemical synthesis of grafted cyclotides using a "plug and play" approach.

Cyclotides are a diverse class of plant-derived cyclic, disulfide-rich peptides with a unique cyclic cystine knot topology. Their remarkable structural stability and resistance to proteolytic degradation can lead to improved pharmacokinetics and oral activity as well as selectivity and high enzymatic stability. Thus, cyclotides have emerged as powerful scaffold molecules for designing peptide-based therapeutics. The chemical engineering of cyclotides has generated novel peptide ligands of G protein-coupled receptors (GPCRs), today's most exploited drug targets. However key challenges potentially limit the widespread use of cyclotides in molecular grafting applications. Folding of cyclotides containing bioactive epitopes remains a major bottleneck in cyclotide synthesis. Here we present a modular 'plug and play' approach that effectively bypasses problems associated with the oxidative folding of cyclotides. By grafting onto a pre-formed acyclic cyclotide-like scaffold we show that difficult-to-graft sequences can be easily obtained and can target GPCRs with nanomolar affinities and potencies. We further show the suitability of this new method to graft other complex epitopes including structures with additional disulfide bonds that are not readily available via currently employed chemical methods, thus fully unlocking cyclotides to be used in drug design applications.

DCRM 2.0: Multispecialty practice recommendations for the management of diabetes, cardiorenal, and metabolic diseases.

The spectrum of cardiorenal and metabolic diseases comprises many disorders, including obesity, type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), dyslipidemias, hypertension, and associated comorbidities such as pulmonary diseases and metabolism dysfunction-associated steatotic liver disease and metabolism dysfunction-associated steatohepatitis (MASLD and MASH, respectively, formerly known as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis [NAFLD and NASH]). Because cardiorenal and metabolic diseases share pathophysiologic pathways, two or more are often present in the same individual. Findings from recent outcome trials have demonstrated benefits of various treatments across a range of conditions, suggesting a need for practice recommendations that will guide clinicians to better manage complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases. To meet this need, we formed an international volunteer task force comprising leading cardiologists, nephrologists, endocrinologists, and primary care physicians to develop the DCRM 2.0 Practice Recommendations, an updated and expanded revision of a previously published multispecialty consensus on the comprehensive management of persons living with DCRM. The recommendations are presented as 22 separate graphics covering the essentials of management to improve general health, control cardiorenal risk factors, and manage cardiorenal and metabolic comorbidities, leading to improved patient outcomes.

Efficacy of a surgical cardiac ablation clamp using nanosecond pulsed electric fields: An acute porcine model.

OBJECTIVE: To examine the effectiveness of a recently developed nonthermal technology, nanosecond pulse-field ablation (nsPFA), for surgical ablation of the atria in a beating heart porcine model. METHODS: Six pigs underwent sternotomy and ablation using an nsPFA parallel clamp. The ablation electrodes (53 mm long) were embedded in the jaws of the clamp. Nine lesions per pig were created in locations chosen to be representative of the Cox-maze procedure. Four lesions were intended to electrically isolate parts of the atrium: the right atrial appendage, left atrial appendage, right pulmonary veins, and left pulmonary veins. For these lesions, exit block testing was performed both after ablation and before euthanasia; the time between the 2 tests was 3.3 ± 0.5 hours (range, 2-4 hours). Using purse string sutures, 5 more lesions were created up to the superior vena cava, down to the inferior vena cava, across the right atrial free wall, and at 2 distinct locations on the left atrial free wall. The clamp delivered a train of nanosecond duration pulses, with a total duration of 2.5 seconds, independent of tissue thickness. The heart tissue was stained with 1% triphenyltetrazolium chloride after a dwelling period of 2 hours. Subsequently, each lesion was cross sectioned at 5-mm intervals to assess the ablation depth and transmurality. In some sections, transmurality could not be established on the basis of triphenyltetrazolium chloride staining alone; for these lesions, Gomori-trichrome stains were used, and the histologic sections were evaluated for transmurality. RESULTS: The ablation time was 2.5 seconds per lesion, for a total of only 22.5 seconds ablation time to create 9 lesions. A total of 53 lesions were created, resulting in 388 separate histologic sections. Transmurality was established in 386 sections (99.5%). Mean tissue thickness was 3.1 ± 1.5 mm (range, 0.2-8.6 mm). Exit block was confirmed in 23 of the 24 lesions (96%) postablation and 23 of 24 (96%) before the animals were humanely killed. Over the course of the procedure, neither pulse-induced arrhythmias nor any other complications were noted. CONCLUSIONS: The novel nsPFA clamp device was effective in creating acute conduction block and transmural lesions in both the right and left atria in an acute porcine model. This nonthermal energy source has great potential to both shorten procedural time and enable effective ablation in the beating heart.

Identification, Elucidation and Deployment of a Cytoplasmic Male Sterility System for Hybrid Potato.

Recent advances in diploid F1 hybrid potato breeding rely on the production of inbred lines using the S-locus inhibitor (Sli) gene. As a result of this method, female parent lines are self-fertile and require emasculation before hybrid seed production. The resulting F1 hybrids are self-fertile as well and produce many undesirable berries in the field. Utilization of cytoplasmic male sterility would eliminate the need for emasculation, resulting in more efficient hybrid seed production and male sterile F1 hybrids. We observed plants that completely lacked anthers in an F2 population derived from an interspecific cross between diploid S. tuberosum and S. microdontum. We studied the antherless trait to determine its suitability for use in hybrid potato breeding. We mapped the causal locus to the short arm of Chromosome 6, developed KASP markers for the antherless (al) locus and introduced it into lines with T and A cytoplasm. We found that antherless type male sterility is not expressed in T and A cytoplasm, proving that it is a form of CMS. We hybridized male sterile al/al plants with P cytoplasm with pollen from al/al plants with T and A cytoplasm and we show that the resulting hybrids set significantly fewer berries in the field. Here, we show that the antherless CMS system can be readily deployed in diploid F1 hybrid potato breeding to improve hybridization efficiency and reduce berry set in the field.

ACR Appropriateness Criteria® Sepsis.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. A search for the underlying cause of infection typically includes radiological imaging as part of this investigation. This document focuses on thoracic and abdominopelvic causes of sepsis. In 2017, the global incidence of sepsis was estimated to be 48.9 million cases, with 11 million sepsis-related deaths (accounting for nearly 20% of all global deaths); therefore, understanding which imaging modalities and types of studies are acceptable or not acceptable is imperative. The 5 variants provided include the most commonly encountered scenarios in the setting of sepsis along with recommendations and data for each imaging study. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

ACR Appropriateness Criteria® Sepsis

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. A search for the underlying cause of infection typically includes radiological imaging as part of this investigation. This document focuses on thoracic and abdominopelvic causes of sepsis. In 2017, the global incidence of sepsis was estimated to be 48.9 million cases, with 11 million sepsis-related deaths (accounting for nearly 20% of all global deaths); therefore, understanding which imaging modalities and types of studies are acceptable or not acceptable is imperative. The 5 variants provided include the most commonly encountered scenarios in the setting of sepsis along with recommendations and data for each imaging study. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Plant-Derived Peptides: (Neglected) Natural Products for Drug Discovery.

Peptides have emerged as key regulators in various physiological processes, including growth, development, stress, and defense responses within plants as well as ecological interactions of plants with microbes and animals. Understanding and harnessing plant peptides can lead to the development of innovative strategies for crop improvement, increasing agricultural productivity, and enhancing resilience to environmental challenges such as drought, pests, and diseases. Moreover, some plant peptides have shown promise in human health applications, with potential therapeutic benefits as ingredients in herbal medicines as well as novel drug leads. The exploration of plant peptides is essential for unraveling the mysteries of plant biology and advancing peptide drug discovery. This short personal commentary provides a very brief overview about the field of plant-derived peptides and a personal word of motivation to increase the number of scientists in pharmacognosy working with these fascinating biomolecules.