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IntroductionGreenness is considered to be a health-promoting feature of both natural and built environments and has the potential to influence mental health outcomes. However, most studies to date have neglected to address whether greenness differentially affects mental health outcomes for individuals across the socioeconomic spectrum. Our study explored if greenness is a moderating factor in the relationship between socioeconomic status (SES) and mental health using data from the Canadian Longitudinal Study on Aging (CLSA).MethodsA cross-sectional design was used to compare mental health outcomes between individuals with different levels of SES and residential greenness. We used self-rated social standing as a measure of SES and depression score measured using the Centre for Epidemiologic Studies 10-Item Depression Scale (CESD-10) as a measure of mental health. Greenness was measured using the annual maximum Normalized Difference Vegetation Index (NDVI) within a 1,000 m buffer area of participants' residential postal code locations.ResultsThere was a statistically significant moderating effect of greenness for the relationship between self-rated social standing and depression score. As greenness increased, individuals with lower self-rated social standing had the greatest decreases in depression score.DiscussionThe results of our study suggests that targeting greening interventions at individuals and communities with low SES may reduce depressive symptoms overall, as well as decrease socioeconomic inequalities in depression.

Background: This case report aims to describe an adverse reaction following intra-arterial melphalan chemotherapy in a 48-year-old female patient with choroidal melanoma. The chemotherapy was part of a phase I clinical trial (MELCOM Study - ClinicalTrials.gov ID: NCT05893654), designed to evaluate its efficacy as a bridge to Ru-106 brachytherapy for treating large uveal melanomas. This is the first reported case of a cutaneous reaction to melphalan in an adult patient. Observations: Upon administration of melphalan, the patient developed an erythematous periorbital skin lesion three days post-treatment. The lesion evolved into a hyperchromic brownish macule that later disappeared spontaneously. Conclusions and Importance: While melphalan successfully reduced the tumor dimensions, making the patient eligible for subsequent Ru-106 brachytherapy, it led to a cutaneous reaction previously reported only in pediatric patients. Despite this aesthetic complication, the therapy was effective in tumor reduction, highlighting the need for further studies to assess the risk-benefit profile of intra-arterial melphalan chemotherapy in adult populations.

Abstract Introduction Tumor genomic testing (TGT) is standard‐of‐care for most patients with advanced/metastatic cancer. Despite established guidelines, patient education prior to TGT is frequently omitted. The purpose of this study was to evaluate the impact of a concise 4 min video for patient education prior to TGT. Methods Based on a quality improvement cycle, an animated video was created to be applicable to any cancer type, incorporating culturally diverse images, available in English and Spanish. Patients undergoing standard‐of‐care TGT were enrolled at a tertiary academic institution and completed survey instruments prior to video viewing (T1) and immediately post‐viewing (T2). Instruments included: (1) 10‐question objective genomic knowledge; (2) 10‐question video message‐specific knowledge; (3) 11‐question Trust in Provider; (4) attitudes regarding TGT. Results A total of 150 participants were enrolled. For the primary objective, there was a significant increase in video message‐specific knowledge (median 10 point increase; p

BackgroundSub-thermoneutral housing increases facultative thermogenesis in mice, which may mask the pre-clinical efficacy of anti-obesity strategies that target energy expenditure (EE). Here, we quantified the impact of protonophore treatment on whole-body energetics in mice housed at 30°C.MethodsC57BL/6J mice (n = 48, 24M/24F) were housed at 24°C for 2 weeks; 32 (16M/16F) were then transitioned to 30°C for a further 4 weeks. Following 2 weeks acclimation at 30°C, mice (n = 16 per group, 8M/8F) received either normal (0 mg/L; Control) or supplemented (400 mg/L; 2,4-Dinitrophenol [DNP]) drinking water. Mice were singly housed in metabolic cages to determine total EE (TEE) and its components via respiratory gas exchange. Mitochondrial respiratory function of permeabilized liver tissue was determined by high-resolution respirometry.ResultsTransitioning mice from 24°C to 30°C reduced TEE and basal EE (BEE) by 16% and 41%, respectively (both P < 0.001). Compared to 30°C controls, TEE was 2.6 kcal/day greater in DNP-treated mice (95% CI: 1.6–3.6 kcal/day, P < 0.001), which was partly due to a 1.2 kcal/day higher BEE in DNP-treated mice (95% CI: 0.6–1.7 kcal/day, P < 0.001). The absolute TEE of 30°C DNP-treated mice was lower than that of mice housed at 24°C in the absence of DNP (DNP: 9.4 ± 0.7 kcal/day vs. 24°C control: 10.4 ± 1.5 kcal/day). DNP treatment reduced overall body fat of females by 2.9 percentage points versus sex-matched controls (95% CI: 1.3%–4.5%, P < 0.001), which was at least partly due to a reduction in inguinal white fat mass.ConclusionProtonophore treatment markedly increases EE in mice housed at 30°C. The magnitude of change in TEE of mice receiving protonophore treatment at 30°C was smaller than that brought about by transitioning mice from 24°C to 30°C, emphasizing that housing temperature must be considered when assessing anti-obesity strategies that target EE in mice.

BackgroundGrowing health care challenges resulting from a rapidly expanding aging population necessitate examining effective rehabilitation techniques that mitigate age-related comorbidity and improve quality of life. To date, exercise is one of a few proven interventions known to attenuate age-related declines in cognitive and sensorimotor functions critical to sustained independence. ObjectiveThis work aims to implement a multimodal imaging approach to better understand the mechanistic underpinnings of the beneficial exercise-induced adaptations to sedentary older adults’ brains and behaviors. Due to the complex cerebral and vascular dynamics that encompass neuroplastic change with aging and exercise, we propose an imaging protocol that will model exercise-induced changes to cerebral perfusion, cerebral vascular reactivity (CVR), and cognitive and sensorimotor task-dependent functional magnetic resonance imaging (fMRI) after prescribed exercise. MethodsSedentary older adults (aged 65-80 years) were randomly assigned to either a 12-week aerobic-based interval-based cycling intervention or a 12-week balance and stretching intervention. Assessments of cardiovascular fitness used the YMCA submaximal VO2 test, basal cerebral perfusion using arterial spin labeling (ASL), CVR using hypercapnic fMRI, and cortical activation using fMRI during verbal fluency and motor tapping tasks. A battery of cognitive-executive and motor function tasks outside the scanning environment will be performed before and after the interventions. ResultsOur studies and others show that improved cardiovascular fitness in older adults results in improved outcomes related to physical and cognitive health as well as quality of life. A consistent but unexplained finding in many of these studies is a change in cortical activation patterns during task-based fMRI, which corresponds with improved task performance (cognitive-executive and motor). We hypothesize that the 12-week aerobic exercise intervention will increase basal perfusion and improve CVR through a greater magnitude of reactivity in brain areas susceptible to neural and vascular decline (inferior frontal and motor cortices) in previously sedentary older adults. To differentiate between neural and vascular adaptations in these regions, we will map changes in basal perfusion and CVR over the inferior frontal and the motor cortices—regions we have previously shown to be beneficially altered during fMRI BOLD (blood oxygen level dependent), such as verbal fluency and motor tapping, through improved cardiovascular fitness. ConclusionsExercise is one of the most impactful interventions for improving physical and cognitive health in aging. This study aims to better understand the mechanistic underpinnings of improved health and function of the cerebrovascular system. If our hypothesis of improved perfusion and cerebrovascular reactivity following a 12-week aerobic exercise intervention is supported, it would add critically important insights into the potential of exercise to improve brain health in aging and could inform exercise prescription for older adults at risk for neurodegenerative disease brought on by cerebrovascular dysfunction. Trial RegistrationClinicalTrials.gov NCT05932069; https://clinicaltrials.gov/study/NCT05932069 International Registered Report Identifier (IRRID)DERR1-10.2196/58316

Invariant natural killer T (iNKT) cells are a subset of lipid-reactive, unconventional T cells that have anti-tumor properties that make them a promising target for cancer immunotherapy. Recent studies have deciphered the developmental pathway of human MAIT and Vγ9Vδ2 γδ-T cells as well as murine iNKT cells, yet our understanding of human NKT cell development is limited. Here, we provide an update in our understanding of how NKT cells develop in the human body and how knowledge regarding their development could enhance human treatments by targeting these cells.

Abstract The three-dimensional domain structure of ferroelectric materials significantly influences their properties. The ferroelectric domain structure of improper multiferroics, such as YMnO3, is driven by a non-ferroelectric order parameter, leading to unique hexagonal vortex patterns and topologically protected domain walls. Characterizing the three-dimensional structure of these domains and domain walls has been elusive, however, due to a lack of suitable imaging techniques. Here, we present a multi-peak Bragg coherent x-ray diffraction imaging determination of the domain structure in single YMnO3 nanocrystals. We resolve two ferroelectric domains separated by a domain wall and confirm that the primary atomic displacements occur along the crystallographic c-axis. Correlation with atomistic simulations confirms the Mexican hat symmetry model of domain formation, identifying two domains with opposite ferroelectric polarization and adjacent trimerization, manifesting in a clockwise arrangement around the hat’s brim.

Abstract Background Immune checkpoint inhibitors (ICIs) have expanded the arsenal of cancer therapeutics over the last decade but are associated with a spectrum of immune-related adverse events (irAEs), including inflammatory arthritis. While these complications are increasingly recognized in the adult population, no cases of inflammatory arthritis irAEs have been reported in the pediatric literature. Case Presentation A 14-year-old female with metastatic epithelioid mesothelioma was referred to the pediatric rheumatology clinic after developing progressive inflammatory joint pain in her bilateral shoulders, hips, and small joints of hands following the second cycle of Nivolumab and Ipilimumab. Initial examinations showed bilateral shoulder joint line tenderness, positive FABERs test bilaterally, tenderness over bilateral greater trochanters, and bilateral second PIP effusions. Her serological profile was notable for positive HLA-B27, positive anti-CCP, negative Rheumatoid Factor, and negative ANA. PET-CT scan performed for disease response following immunotherapy showed symmetric increased metabolic activity primarily involving the supraspinatus, gluteus medius and minimus, and semimembranosus tendon insertions. Her presentation was consistent with a grade 1 irAE that worsened to a grade 2 irAE despite NSAID therapy, prompting a short course of oral prednisolone. She achieved clinical remission of her mesothelioma following six cycles of Nivolumab and Ipilimumab and her inflammatory arthritis was controlled on Celebrex monotherapy. Conclusions To our knowledge, this is the first pediatric case of ICI-induced inflammatory arthritis and enthesitis. This case highlights the importance of increasing awareness of diagnosis and management of irAEs in children.

Abstract Background Untranslated regions (UTRs) are important mediators of post-transcriptional regulation. The length of UTRs and the composition of regulatory elements within them are known to vary substantially across genes, but little is known about the reasons for this variation in humans. Here, we set out to determine whether this variation, specifically in 5’UTRs, correlates with gene dosage sensitivity. Results We investigate 5’UTR length, the number of alternative transcription start sites, the potential for alternative splicing, the number and type of upstream open reading frames (uORFs) and the propensity of 5’UTRs to form secondary structures. We explore how these elements vary by gene tolerance to loss-of-function (LoF; using the LOEUF metric), and in genes where changes in dosage are known to cause disease. We show that LOEUF correlates with 5’UTR length and complexity. Genes that are most intolerant to LoF have longer 5’UTRs, greater TSS diversity, and more upstream regulatory elements than their LoF tolerant counterparts. We show that these differences are evident in disease gene-sets, but not in recessive developmental disorder genes where LoF of a single allele is tolerated. Conclusions Our results confirm the importance of post-transcriptional regulation through 5'UTRs in tight regulation of mRNA and protein levels, particularly for genes where changes in dosage are deleterious and lead to disease. Finally, to support gene-based investigation we release a web-based browser tool, VuTR, that supports exploration of the composition of individual 5'UTRs and the impact of genetic variation within them.

Metal complexes of 3,5-diisopropylsalicylate are reported to have anti-inflammatory and anti-convulsant activities. The title binuclear copper complex, [Cu2(C13H17O3)4(C2H6OS)2] or [Cu(II)2(3,5-DIPS)4(DMSO)2], contains two five-coordinate copper atoms that are bridged by four 3,5-diisopropylsalicylate ligands and capped by two axial dimethyl sulfoxide (DMSO) moieties. Each copper atom is attached to four oxygen atoms in an almost square-planar fashion, with the addition of a DMSO ligand in an apical position leading to a square-pyramidal arrangement. The hydroxy group of the diisopropylsalicylate ligands participates in intramolecular O—H...O hydrogen-bonding interactions.

Abstract Analysis of DNA methylation in cell-free DNA reveals clinically relevant biomarkers but requires specialized protocols such as whole-genome bisulfite sequencing. Meanwhile, millions of cell-free DNA samples are being profiled by whole-genome sequencing. Here, we develop FinaleMe, a non-homogeneous Hidden Markov Model, to predict DNA methylation of cell-free DNA and, therefore, tissues-of-origin, directly from plasma whole-genome sequencing. We validate the performance with 80 pairs of deep and shallow-coverage whole-genome sequencing and whole-genome bisulfite sequencing data.

Background Incidental findings are commonly noted in advanced imaging studies. Few data exist regarding the rate of incidental findings on computed tomography (CT) for preoperative shoulder arthroplasty planning. This study aims to identify the incidence of these findings and the rate at which they warrant further work-up to help guide orthopedic surgeons in counseling patients. Methods A retrospective review was performed to identify patients with available preoperative shoulder CT who subsequently underwent shoulder arthroplasty procedures at a single institution between 2015 and 2021. Data including age, sex, and smoking status were obtained. Radiology reports for CTs were reviewed for incidental findings and categorized based on location, tissue type, and/or body system. The rate of incidental findings and the rate at which further follow-up was recommended by the radiologist were determined. Results A total of 617 patients was identified. There were 173 incidental findings noted in 146 of these patients (23.7%). Findings ranged from pulmonary (59%), skin/soft tissue (16%), thyroid (13%), vascular (9%), spinal (2%), and abdominal (1%) areas. Of the pulmonary findings, 50% were pulmonary nodules and 47% were granulomatous disease. Overall, the final radiology report recommended further follow-up for 50% of the patients with incidental findings. Conclusions Incidental findings are relatively common in preoperative CTs obtained for shoulder arthroplasty, occurring in nearly one-quarter of patients. Most of these findings are pulmonary in nature. Overall, half of the patients with incidental findings were recommended for further follow-up. These results establish population data to guide orthopedic surgeons in patient counseling. Level of evidence III.

Abstract Understanding the Hubbard model is crucial for investigating various quantum many-body states and its fermionic and bosonic versions have been largely realized separately. Recently, transition metal dichalcogenides heterobilayers have emerged as a promising platform for simulating the rich physics of the Hubbard model. In this work, we explore the interplay between fermionic and bosonic populations, using a WS2/WSe2 heterobilayer device that hosts this hybrid particle density. We independently tune the fermionic and bosonic populations by electronic doping and optical injection of electron-hole pairs, respectively. This enables us to form strongly interacting excitons that are manifested in a large energy gap in the photoluminescence spectrum. The incompressibility of excitons is further corroborated by observing a suppression of exciton diffusion with increasing pump intensity, as opposed to the expected behavior of a weakly interacting gas of bosons, suggesting the formation of a bosonic Mott insulator. We explain our observations using a two-band model including phase space filling. Our system provides a controllable approach to the exploration of quantum many-body effects in the generalized Bose-Fermi-Hubbard model.

Flooding in urban areas is expected to become even more common due to climatic changes, putting pressure on cities to implement effective response measures. Practical mechanisms for assessing flood risk have become highly desired, but existing solutions have been devoted to evaluating only specific cities and consider only limited risk perspectives, constraining their general applicability. This article presents an innovative approach for assessing the flood risk of delimited urban areas by exploiting geospatial information from publicly available databases, providing a method that is applicable to any city in the world and requiring minimum configurations. A set of mathematical equations is defined for numerically assessing risk levels based on elevation, slope, and proximity to rivers, while the existence of emergency-related urban infrastructure is considered as a risk reduction factor. Then, computed risk levels are used to classify areas, allowing easy visualisation of flood risk for a city. This smart city approach not only serves as a valuable tool for assessing the expected flood risk based on different parameters but also facilitates the implementation of cutting-edge strategies to effectively mitigate critical situations, ultimately enhancing urban resilience to flood-related disaster.

Abstract The cerebral cortex is vital for the processing and perception of sensory stimuli. In the somatosensory axis, information is received primarily by two distinct regions, the primary (S1) and secondary (S2) somatosensory cortices. Top-down circuits stemming from S1 can modulate mechanical and cooling but not heat stimuli such that circuit inhibition causes blunted perception. This suggests that responsiveness to particular somatosensory stimuli occurs in a modality specific fashion and we sought to determine additional cortical substrates. In this work, we identify in a mouse model that inhibition of S2 output increases mechanical and heat, but not cooling sensitivity, in contrast to S1. Combining 2-photon anatomical reconstruction with chemogenetic inhibition of specific S2 circuits, we discover that S2 projections to the secondary motor cortex (M2) govern mechanical and heat sensitivity without affecting motor performance or anxiety. Taken together, we show that S2 is an essential cortical structure that governs mechanical and heat sensitivity.

Abstract Natural aerosol feedbacks are expected to become more important in the future, as anthropogenic aerosol emissions decrease due to air quality policy. One such feedback is initiated by the increase in biogenic volatile organic compound (BVOC) emissions with higher temperatures, leading to higher secondary organic aerosol (SOA) production and a cooling of the surface via impacts on cloud radiative properties. Motivated by the considerable spread in feedback strength in Earth System Models (ESMs), we here use two long-term observational datasets from boreal and tropical forests, together with satellite data, for a process-based evaluation of the BVOC-aerosol-cloud feedback in four ESMs. The model evaluation shows that the weakest modelled feedback estimates can likely be excluded, but highlights compensating errors making it difficult to draw conclusions of the strongest estimates. Overall, the method of evaluating along process chains shows promise in pin-pointing sources of uncertainty and constraining modelled aerosol feedbacks.

Abstract Background/aims We aimed to develop a validated patient-reported Gastrointestinal Health Scale (GHS) specific to MECP2 Duplication Syndrome (MDS) to be used in clinical trials. Methods MDS parents completed a Gastrointestinal Health Questionnaire (GHQ) to investigate the most relevant and important items associated with gastrointestinal problems in MECP2-related disorders. Item reduction was executed according to EORTC guidelines. We performed reliability and validity studies for the finalized scale. Results A total of 106 surveys were eligible for item reduction and validation processes. The initial 55 items were reduced to 38 items based on parent responses, expert opinion, and initial confirmatory factor analysis (CFA). The final MDS-specific GHS included 38 items and 7 factors that underwent further reliability and validity assessments. The power of the study was at least 0.982. The Cronbach’s alphas of the instruments were General Health: 0.799, Eating-Chewing-Swallowing: 0.809, Reflux: 0.794, Motility: 0.762, Mood: 0.906, Medication: 0.595, Parenting: 0.942 and all items together: 0.928. The correlation coefficient between total and individual item scores ranged from 0.215 to 0.730. Because of the ordinal nature of the variables, the diagonal weighted least squares estimation (DWLS) method was used to execute the CFA and Structural Equation Modeling. The GHS had excellent model fit with the acceptable range of fit indices values. Conclusions We developed a parent-reported, reliable, and valid MDS-specific GHS. This scale can be utilized in clinical settings or as an outcome measure in translational and clinical research.

Ergot alkaloids are fungal natural products with important roles in agriculture and medicine. We used heterologous expression and gene knockout approaches to investigate potential roles for the product of a major facilitator superfamily transporter gene (easT) recently found in an ergot alkaloid biosynthetic gene cluster in Aspergillus leporis. A strain of Aspergillus fumigatus previously engineered to accumulate lysergic acid, but which did not convert the precursor agroclavine to lysergic acid efficiently or secrete lysergic acid well, was chosen as an expression host for easT. Expression of easT in this strain resulted in accumulation of significantly more pathway intermediates but no detectable lysergic acid. Secretion of ergot alkaloids was reduced in the easT-expressing strain. EasT localized to discrete vesicle-like structures in the cytosol of A. fumigatus, with no localization detected in the plasma membrane. When easT was knocked out in A. leporis, accumulation of lysergic acid amides was reduced relative to the wild type. There was no negative effect on secretion of ergot alkaloids in the knockout mutant. The data indicate that easT encodes a product that contributes to accumulation of ergot alkaloids, perhaps by transporting intermediates between cellular compartments, but does not have a significant role in secreting ergot alkaloids.

Antecedentes: El cuestionario de discapacidad de brazo, hombro y mano (DASH, Disabilities of the Arm, Shoulder and Hand) mide el impacto de patologías del miembro superior en la calidad de vida. Sin embargo, su uso en la población mexicana no ha sido formalmente validado. Objetivo: Realizar la adaptación cultural y validación del cuestionario DASH para conocer la perspectiva de pacientes con trastornos neurogénicos del miembro superior respecto al impacto en su calidad de vida. Método: Se realizó una adaptación al vocabulario mexicano de la versión española del cuestionario DASH y se aplicó en 478 voluntarios. Se estimaron el efecto techo, el efecto suelo, la correlación ítem-total, las medidas de tendencia central de ítems y el puntaje total, la consistencia interna, la precisión y la validez transversal y longitudinal mediante la comparación de individuos sanos y enfermos con diferente nivel de discapacidad. Resultados: Nuestra versión del cuestionario DASH resultó equivalente a las previamente aprobadas y mostró homogeneidad de los ítems respecto al valor total del cuestionario (alfa de Cronbach > 0.96). Además, tuvo una precisión de 7.25 puntos y se documentó la validez transversal y longitudinal con diferencias significativas entre grupos y subgrupos con diferente nivel de discapacidad. Conclusiones: El cuestionario DASH puede ser empleado con un nivel de confianza alto en la población mexicana.

Invasive lobular breast cancer (ILC) is characterized by a relatively high risk for late recurrence and a unique metastatic pattern with an increased risk for metastasis to gynecologic organs and peritoneum. We present a unique case of recurrent ILC with metastasis to the abdominal peritoneum as well as the uterine myometrium and cervix. Treatment was complicated by the discovery of concomitant uterine carcinosarcoma. This patient was effectively treated with a combination of hormonal therapy for her metastatic ILC and a combination of chemotherapy and immunotherapy for uterine carcinosarcoma. Molecular evaluation revealed a characteristic CDH1 mutation within the ILC and a PI3KCA mutation within the uterine carcinosarcoma, both of which have been linked to epithelial-to-mesenchymal transitions. Examination of the tumor immune microenvironment revealed proportionally more cytotoxic NK cells. This robust immune infiltration may be an indicator of the response to immunotherapy observed in this tumor or a result of the metastatic breast cancer within the uterus. This report provides a characterization of the molecular and immunologic landscape in this case with metastatic ILC and uterine carcinosarcoma.

Le Dantec virus (LDV), assigned to the species Ledantevirus ledantec, genus Ledantevirus, family Rhabdoviridae has been associated with human disease but has gone undetected since the 1970s. We describe the detection of LDV in a human case of undifferentiated fever in Uganda by metagenomic sequencing and demonstrate a serological response using ELISA and pseudotype neutralisation. By screening 997 individuals sampled in 2016, we show frequent exposure to ledanteviruses with 76% of individuals seropositive in Western Uganda, but lower seroprevalence in other areas. Serological cross-reactivity as measured by pseudotype-based neutralisation was confined to ledanteviruses, indicating population seropositivity may represent either exposure to LDV or related ledanteviruses. We also describe the discovery of a closely related ledantevirus in blood from the synanthropic rodent Mastomys erythroleucus. Ledantevirus infection is common in Uganda but is geographically heterogenous. Further surveys of patients presenting with acute fever are required to determine the contribution of these emerging viruses to febrile illness in Uganda.

Understanding the dynamics between climate change and human adaptive strategies is a longstanding question driving paleoecological and archaeological research in North America's Great Basin. We present multiproxy data from five sediment cores retrieved from Paulina Marsh in the Fort Rock Basin, Oregon, an area renowned for its archaeology but lacking the paleoenvironmental data needed to fully contextualize those records. Radiocarbon, pollen, particle size, elemental, and charcoal analyses of one core, and geochronological data from four additional cores, reveal fluctuating vegetation communities, hydrologic conditions, and fire histories during the Early and Late Holocene that are consistent with models proposed to explain changing settlement-subsistence patterns in the region. There was likely an emergent marsh or meadow and an absence of Juniperus at the core site during the Early Holocene. Middle Holocene deposits are not present due to a geologic unconformity, perhaps because of channel migration and climatic aridity. Late Holocene sediments record a more mesic meandering stream system between ∼3900 and 2200 years ago, followed by an increase in xeric-adapted vegetation in the last 2000 years. The lack of Juniperus pollen in the Early Holocene sediments inform ongoing debates about Juniperus spread in the Great Basin. These data represent the first Early Holocene pollen record from the Fort Rock Basin and are one of few lowland vegetation histories of this age in the region. This study contributes to our understanding of past ecology in semi-arid environments, provides new context for archaeological interpretations, and establishes a framework for future work in the region.

ObjectiveDespite the need, measuring glomerular filtration rate (mGFR) is not routinely performed for adults with cerebral palsy (CP), possibly due to unknown feasibility given the secondary complications of CP. This study aimed to assess the feasibility and reliability of mGFR and explore factors associated with eGFR-mGFR discordance among young adults with mild-to-moderate CP.MethodsThis single-center, cross-sectional study included 18- to 40-year-olds with CP gross motor function classification system (GMFCS) I-III. The participants were excluded if they were pregnant/lactating, had cognitive impairments, or had contraindications to mGFR. A routine clinical protocol for mGFR and eGFR was used. mGFR feasibility was assessed based on the number of participants who completed testing. mGFR reliability was assessed using the coefficient of variation (CV) across the four 30 min intervals. The association between age, sex, and GMFCS and the percentage of eGFR-mGFR discordance was assessed.ResultsOf the 19 participants enrolled, 18 completed the testing [mean age (SD), 29.9 (7.4) years, n = 10 female participants, n = 10/3/5 for GMFCS I/II/III] and most (n = 15) of the participants had an mGFR >90 mL/min; 14 participants (77.8%) had a CV 50%. eGFR overestimated mGFR by a median (interquartile range) of approximately 17.5% (2–38%); the full range of mis-estimation was −20.5 to 174.3%. Increasing age and GMFCS levels exhibited notable, but weak-to-modest, associations with a larger eGFR-mGFR discordance.DiscussionObtaining mGFR was feasible and reasonably reliable within this small sample. eGFR overestimated mGFR by a notable amount, which may be associated with patient-level factors.

Background: Blood pressure control is critical for older adults because the prevalence of hypertension and resulting cardiovascular illness increases with age. Antihypertension medications are central to blood pressure treatment. However, nonadherence to antihypertension medications is high. Health technology such as smartphone apps provide an opportunity for users to manage their medication regimen and support processes related to medication-taking. Objective: We implemented a user-centered evaluation approach to develop and refine adherence feedback visualizations for the MEDSReM© medication adherence app for older adults with hypertension. Methods: We conducted a literature review and iterative usability testing to achieve this objective. We identified adherence goals, information needs, as well as design guidelines by reviewing theoretical frameworks and existing scientific evidence. We then used a two-phase iterative user-centered study and subject matter expert evaluation. Both quantitative and qualitative data were used to select and improve the current prototype and evolve to the next prototype. Results: The need for daily, weekly, and monthly adherence performance information as well as visualization formats for conveying this information was identified from the literature review. Overall, the information shown in visualization prototypes was successfully interpreted by participants. Comprehension issues of visualizations were identified and addressed from visual prototype revisions. Insights from both user and subject matter expert groups were used to select and refine the prototypes for the MEDSReM app. Conclusion: Evidence-based and user-centered approaches were effective for developing visualizations about adherence performance feedback in the MEDSReM app and provided insight into how the app can be made easy to understand and use by older adults with hypertension, which will be evaluated in future effectiveness testing.

Abstract Despite its perceived historical rarity, fire is an important disturbance in tropical rainforests. Very large rainforest fires have been observed multiple times in recent decades, often during years of strong El Niño‐Southern Oscillation droughts. Fire in rainforest has major short‐term consequences for humans and wildlife by converting forest to fire‐prone fern, shrub, and grass, but the long‐term effects remain to be seen. Borneo's indigenous groups have been using fire to clear land for centuries, yet the prevalence and spatial patterns of premodern fire across forest types in Borneo are not well understood. This research set out to reconstruct fire in a 1500‐ha primary rainforest spanning 800 m of elevation in Indonesian Borneo with the goal of elucidating the role humans have played in rainforest fire. We found that humans played an important role in the occurrence of fire in recent centuries. Evidence of fire—charcoal >2 mm—is more abundant in forest types where humans would be more likely to live and/or practice swidden agriculture. However, pyrogenic material is ubiquitous across the study area, showing that all forest types have experienced fire. A set of 50 radiocarbon dates showed that in lowland areas—where human‐caused fire is most likely—fire occurred throughout the last 3200 years, peaking 1300–1600 ce. The upland areas lacked evidence of fire before 1250 ce but otherwise had a similar pattern to the lowlands. The period of high fire coincides with regional demographic changes as well as regional droughts documented elsewhere in Southeast Asia. In upland areas, fires likely burned only under regional drought when fires could more easily spread upslope. Although forest plot studies at this site show little structural evidence of past fires, tree diversity is lower than expected in the most burned areas (alluvial benches). Thus, our results suggest that land clearance was a major source of fire, but the current intact state of these rainforests indicates that they were largely resilient to fires and land use hundreds of years ago. Recent fires mirror patterns of fire spread that occurred hundreds of years ago, though their severity and extent are likely much greater.

Abstract Background The optimal adjuvant endocrine therapy (ET) in hormone receptor positive (HR+) and human epidermal growth factor receptor 2 positive (HER2+) premenopausal breast cancer (BC) remains unclear. Moreover, the benefit and clinical indications of ovarian suppression (OS) is poorly elucidated. We described real‐world patterns surrounding choice of ET and clinicopathologic features which predicted treatment with OS in a contemporary cohort of premenopausal women with HR+/HER2+ BC. Methods This retrospective analysis included premenopausal patients with nonmetastatic HR+/HER2+ BC from the CancerLinQ Discovery database from January 2010 to May 2020. Women were less than 50 years and received chemotherapy, anti‐HER2 therapy, and ET. They were categorized into 1 of 4 groups based on type of ET prescribed at initiation: aromatase inhibitor (AI) + OS, OS, tamoxifen + OS, or tamoxifen. Multivariable logistic regression assessed associations between clinicopathologic features and OS use. Results Out of 360,540 patients with BC, 937 were included. The majority (n = 818, 87%) were prescribed tamoxifen, whereas 4 (0.4%), 50 (5.3%), and 65 (6.9%) received OS, tamoxifen + OS and AI + OS, respectively. No clinicopathologic features predicted OS use apart from age; patients

Summary: Early modern humans lived as hunter-gatherers for millennia before agriculture, yet the genetic adaptations of these populations remain a mystery. Here, we investigate selection in the ancient hunter-gatherer-fisher Jomon and contrast pre- and post-agricultural adaptation in the Japanese archipelago. Building on the successful validation of imputation with ancient Asian genomes, we identify selection signatures in the Jomon, particularly robust signals from KITLG variants, which may have influenced dark pigmentation evolution. The Jomon lacks well-known adaptive variants (EDAR, ADH1B, and ALDH2), marking their emergence after the advent of farming in the archipelago. Notably, the EDAR and ADH1B variants were prevalent in the archipelago 1,300 years ago, whereas the ALDH2 variant could have emerged later due to its absence in other ancient genomes. Overall, our study underpins local adaptation unique to the Jomon population, which in turn sheds light on post-farming selection that continues to shape contemporary Asian populations.

Background Dietary diversity is key in determining the quality of a person’s diet by including the consumption of several food groups. Vegetable gardening is a holistic approach to producing nutritious food and reducing food insecurity. Higher vegetable consumption is closely associated with better diet quality and dietary diversity score. Objective This study aims to analyze the vegetable consumption and diet diversity of households with vegetable gardens and households without vegetable gardens. Methods The study used a quantitative method and a descriptive and inferential research design. Given the specific profile of respondents, purposive sampling was employed. However, quotas per profile were set. The data were collected using quantitative tools such as guided questionnaires and a 24-hour dietary recall questionnaire. Results The majority of the gardeners were female, ages 54 to 64, mainly living in the Barangay UP campus, with high school as their highest educational attainment. The non-gardeners were Vegetable gardeners who earned less than ₱20,000 compared to the non-gardeners who earned. Vegetable gardeners were likelier to meet the recommended vegetable consumption and had a higher Dietary Diversity Score. Conclusions The respondents who met the recommended vegetable intake of three to five servings were mostly vegetable gardeners. Thus, vegetable gardening aids in increasing the vegetable consumption of households because of the accessibility they have to nutritious foods compared to households that do not practice home gardening.

The Probabilistic Reward Task (PRT) is widely used to investigate the impact of Major Depressive Disorder (MDD) on reinforcement learning (RL), and recent studies have used it to provide insight into decision-making mechanisms affected by MDD. The current project used PRT data from unmedicated, treatment-seeking adults with MDD to extend these efforts by: (1) providing a more detailed analysis of standard PRT metrics—response bias and discriminability—to better understand how the task is performed; (2) analyzing the data with two computational models and providing psychometric analyses of both; and (3) determining whether response bias, discriminability, or model parameters predicted responses to treatment with placebo or the atypical antidepressant bupropion. Analysis of standard metrics replicated recent work by demonstrating a dependency between response bias and response time (RT), and by showing that reward totals in the PRT are governed by discriminability. Behavior was well-captured by the Hierarchical Drift Diffusion Model (HDDM), which models decision-making processes; the HDDM showed excellent internal consistency and acceptable retest reliability. A separate “belief” model reproduced the evolution of response bias over time better than the HDDM, but its psychometric properties were weaker. Finally, the predictive utility of the PRT was limited by small samples; nevertheless, depressed adults who responded to bupropion showed larger pre-treatment starting point biases in the HDDM than non-responders, indicating greater sensitivity to the PRT’s asymmetric reinforcement contingencies. Together, these findings enhance our understanding of reward and decision-making mechanisms that are implicated in MDD and probed by the PRT.

The urbanisation of the last century has created a significant demand for urban areas to deliver public services that are efficient, sustainable, and adaptable. This demand is further amplified by the anticipated impacts of climate change and the complexities introduced by rapidly expanding urban populations. In this scenario, smart city initiatives have emerged as a pivotal strategy to address these challenges, leveraging innovative technologies and paradigms such as Internet of Things, Artificial Intelligence, and Data Science to improve the quality of urban life in a more sustainable way. Recently, research efforts in these domains have focused on creating systems that can adapt and respond to changing conditions, enabling greater adaptivity and responsiveness to the needs of urban landscapes. Therefore, this article provides a comprehensive survey of adaptive urban services within a smart city context. Through analyses of recent literature, we investigate the technological foundations that enable the adaptivity of urban services and explore their applications in various urban scenarios, including energy, mobility, emergency management, public safety, and waste management. This article also highlights the benefits of adopting adaptive urban services, such as improved traffic management, resilient emergency management, and enhanced citizen engagement, bringing an important contribution to this broad research area. Finally, we provide a discussion on current technology enablers and challenges and present an overview for future research directions on adaptive urban systems at the forefront of transforming cities into more intelligent ecosystems.

Marine protected areas (MPAs) are critical in safeguarding biodiversity and ecosystem functions under climate change. The long-term effectiveness of these static conservation measures will depend on how well they represent current and future ocean changes. Here, we use the Climate Risk Index for Biodiversity to assess the vulnerability representation of marine ecosystems within the Canadian marine conservation network (CMCN) under two divergent emissions scenarios. We found that MPAs best represent climate vulnerability in Atlantic Canada (85% representativity overall, and 93% in the Gulf of Saint Lawrence under low emissions), followed by the Pacific (78%) and Arctic (63%; lowest in the Eastern Arctic (41% under high emissions) regions). Notably, MPAs with lower climate vulnerability are proportionally overrepresented in the CMCN. Broad-scale geographic targets employed in the Scotian Shelf-Bay of Fundy network planning process achieve over 90% representativity of climate vulnerabilities, underscoring the importance of ensuring habitat representativity and geographic distribution in conservation planning to enhance climate resilience, even if not explicitly prioritized. Moving towards Canada’s target to protect 30% of its waters by 2030, prioritizing representativity and designation of MPAs in currently underrepresented climate-vulnerable regions may be crucial to enhancing the resilience of the CMCN amidst an ever-changing climate.

Abstract Background The growth of urban dwelling populations globally has led to rapid increases of research and policy initiatives addressing associations between the built environment and physical activity (PA). Given this rapid proliferation, it is important to identify priority areas and research questions for moving the field forward. The objective of this study was to identify and compare research priorities on the built environment and PA among researchers and knowledge users (e.g., policy makers, practitioners). Methods Between September 2022 and April 2023, a three-round, modified Delphi survey was conducted among two independent panels of international researchers (n = 38) and knowledge users (n = 23) to identify similarities and differences in perceived research priorities on the built environment and PA and generate twin ‘top 10’ lists of the most important research needs. Results From a broad range of self-identified issues, both panels ranked in common the most pressing research priorities including stronger study designs such as natural experiments, research that examines inequalities and inequities, establishing the cost effectiveness of interventions, safety and injuries related to engagement in active transportation (AT), and considerations for climate change and climate adaptation. Additional priorities identified by researchers included: implementation science, research that incorporates Indigenous perspectives, land-use policies, built environments that support active aging, and participatory research. Additional priorities identified by knowledge users included: built environments and PA among people living with disabilities and a need for national data on trip chaining, multi-modal travel, and non-work or school-related AT. Conclusions Five common research priorities between the two groups emerged, including (1) to better understand causality, (2) interactions with the natural environment, (3) economic evaluations, (4) social disparities, and (5) preventable AT-related injuries. The findings may help set directions for future research, interdisciplinary and intersectoral collaborations, and funding opportunities.

Abstract Background Those experiencing houselessness rely on obtaining food from community organizers and donations. Simultaneously, the houseless face disproportionally high rates of medical conditions that may be affected by diet including diabetes, hypertension, and hyperlipidemia. There is limited literature on the resources and barriers of the houseless community regarding optimal nutrition from an actionable perspective. Further, less data is available on how street medicine organizations may best impact the nutrition of the unhoused they serve. Elucidating this information will inform how organizational efforts may best support the nutrition of the houseless community. Methods In partnership with the medical student-run organization, Chicago Street Medicine, at Northwestern University Feinberg School of Medicine, twenty adults experiencing houselessness in Chicago, Illinois participated in the cross-sectional study. A 10-item survey was verbally administered to characterize the participants’ daily food intake, food sources, barriers, resources, and nutritional preferences and needs. All data was directly transcribed into REDCap. Descriptive statistics were generated. Results Individuals consumed a median of 2 snacks and meals per day (IQR: 1–3). No participant consumed adequate servings of every food group, with only one participant meeting the dietary intake requirements for one food group. Participants most often received their food from donations (n = 15), purchasing themselves (n = 11), food pantries (n = 4), and shelters (n = 3). Eleven of nineteen participants endorsed dental concerns as a major barrier to consuming certain foods. Twelve participants had access to a can opener and twelve could heat their meals on a stove or microwave. Seven had access to kitchen facilities where they may prepare a meal. Approximately half of participants had been counseled by a physician to maintain a particular diet, with most related to reducing sugar intake. Conclusion Most houseless participants were unable to acquire a balanced diet and often relied on organizational efforts to eat. Organizations should consider the chronic health conditions, dentition needs, and physical resources and barriers to optimal nutrition when obtaining food to distribute to the unhoused.

Abstract Cell‐Free Protein Synthesis (CFPS) has, over the past decade, seen a substantial increase in interest from both academia and industry. Applications range from fundamental research, through high‐throughput screening to niche manufacture of therapeutic products. This review/perspective focuses on Quality Control in CFPS. The importance and difficulty of measuring the Raw Material Attributes (RMAs) of whole cell extract, such as constituent protein and metabolite concentrations, and of understanding and controlling these complicated enzymatic reactions is explored, for both centralised and distributed industrial production of biotherapeutics. It is suggested that a robust cell‐free extract production process should produce cell extract of consistent quality; however, demonstrating this is challenging without a full understanding of the RMAs and their interaction with reaction conditions and product. Lack of technology transfer and knowledge sharing is identified as a key limiting factor in the development of CFPS. The article draws upon the experiences of industrial process specialists, discussions within the Future Targeted Healthcare Manufacturing Hub Specialist Working Groups and evidence drawn from various sources to identify sources of process variation and to propose an initial guide towards systematisation of CFPS process development and reporting. These proposals include the development of small scale screening tools, consistent reporting of selected process parameters and analytics and application of industrial thinking and manufacturability to protocol development.

In a genomic study by Chan and colleagues, pit-vipers of the Trimeresurus erythrurus–purpureomaculatus complex from the Ayeyarwady and Yangon regions in Myanmar were demonstrated to be a distinct species based on robust population genetic and species delimitation analyses. Here, we provide morphological characterizations and a formal description of those populations as a new species. The new species, Trimeresurus ayeyarwadyensis sp. nov., is most closely related to T. erythrurus and T. purpureomaculatus and shares morphological characteristics with both of those species. Some specimens of T. ayeyarwadyensis sp. nov. have green dorsal coloration and no distinct dorsal blotches (a trait shared with T. erythrurus but not T. purpureomaculatus), while others have dark dorsal blotches (a trait shared with T. purpureomaculatus but not T. erythrurus). The distinct evolutionary trajectory of the new species, coupled with the lack of obvious morphological differentiation, represents a classic example of the cryptic nature of species commonly found in the Trimeresurus group of Asian pit-vipers and underscores the need for data-rich analyses to verify species’ boundaries more broadly within this genus.

Abstract Early newborn care provided in the first 2 days of life is critical in reducing neonatal morbidity and mortality. This care can be used to monitor and evaluate the content and quality of neonatal postnatal care. This study aimed to identify determinants and geographic distributions of early newborn care uptake in Ethiopia. We used data from the 2019 Ethiopian Mini Demographic and Health Survey (EMDHS). We conducted a multilevel binary logistic regression model and geographic analysis to identify the determinants of receiving early newborn care. A total of 2105 children were included in the study. Of the included children, 39.6% (95% confidence interval (CI) 38%, 42%) received at least two components of early newborn care services in the first 2 days after birth. Greater odds of receiving early newborn care were experienced by infants to mothers with secondary or above education (adjusted odds ratio (AOR) = 1.72; 95% CI 1.44, 2.18), from households with highest wealth quantiles (AOR = 1.47; 95% CI 1.16, 1.79), with at least one antenatal care contact (AOR = 2.73; 95% CI 1.79, 4.16), with birth at health facility (AOR = 25.63; 95% CI 17.02, 38.60), and those births through cesarean section (AOR = 2.64; 95% CI 1.48, 4.71). Substantial geographic variation was observed in the uptake of early newborn care in Ethiopia. Several individual- and community-level factors were associated with newborn postnatal care. Policymakers should prioritise these areas and the enhancement of postnatal healthcare provisions for mothers with low socioeconomic status.

Abstract Exciton polaritons are quasiparticles of photons coupled strongly to bound electron-hole pairs, manifesting as an anti-crossing light dispersion near an exciton resonance. Highly anisotropic semiconductors with opposite-signed permittivities along different crystal axes are predicted to host exotic modes inside the anti-crossing called hyperbolic exciton polaritons (HEPs), which confine light subdiffractionally with enhanced density of states. Here, we show observational evidence of steady-state HEPs in the van der Waals magnet chromium sulfide bromide (CrSBr) using a cryogenic near-infrared near-field microscope. At low temperatures, in the magnetically-ordered state, anisotropic exciton resonances sharpen, driving the permittivity negative along one crystal axis and enabling HEP propagation. We characterize HEP momentum and losses in CrSBr, also demonstrating coupling to excitonic sidebands and enhancement by magnetic order: which boosts exciton spectral weight via wavefunction delocalization. Our findings open new pathways to nanoscale manipulation of excitons and light, including routes to magnetic, nonlocal, and quantum polaritonics.

Abstract Background Marburg virus disease is an acute haemorrhagic fever caused by Marburg virus. Marburg virus is zoonotic, maintained in nature in Egyptian fruit bats, with occasional spillover infections into humans and nonhuman primates. Although rare, sporadic cases and outbreaks occur in Africa, usually associated with exposure to bats in mines or caves, and sometimes with secondary human-to-human transmission. Outbreaks outside of Africa have also occurred due to importation of infected monkeys. Although all previous Marburg virus disease outbreaks have been brought under control without vaccination, there is nevertheless the potential for large outbreaks when implementation of public health measures is not possible or breaks down. Vaccines could thus be an important additional tool, and development of several candidate vaccines is under way. Methods We developed a branching process model of Marburg virus transmission and investigated the potential effects of several prophylactic and reactive vaccination strategies in settings driven primarily by multiple spillover events as well as human-to-human transmission. Linelist data from the 15 outbreaks up until 2022, as well as an Approximate Bayesian Computational framework, were used to inform the model parameters. Results Our results show a low basic reproduction number which varied across outbreaks, from 0.5 [95% CI 0.05–1.8] to 1.2 [95% CI 1.0–1.9] but a high case fatality ratio. Of six vaccination strategies explored, the two prophylactic strategies (mass and targeted vaccination of high-risk groups), as well as a combination of ring and targeted vaccination, were generally most effective, with a probability of potential outbreaks being terminated within 1 year of 0.90 (95% CI 0.90–0.91), 0.89 (95% CI 0.88–0.90), and 0.88 (95% CI 0.87–0.89) compared with 0.68 (0.67–0.69) for no vaccination, especially if the outbreak is driven by zoonotic spillovers and the vaccination campaign initiated as soon as possible after onset of the first case. Conclusions Our study shows that various vaccination strategies can be effective in helping to control outbreaks of MVD, with the best approach varying with the particular epidemiologic circumstances of each outbreak.

Reply to the discussion and comments of Azerêdo et al. (2023) and Schneider et al. (2023).

Oxaliplatin is successfully used on advanced colorectal cancer to eradicate micro-metastasis, whereas its benefits in the early stages of colorectal cancer remains controversial since approximately 30% of patients experience unexpected relapses. Herein, we evaluate the efficacy of oxidative phosphorylation as a predictive biomarker of oxaliplatin response in colorectal cancer. We found that non-responding patients exhibit low oxidative phosphorylation activity, suggesting a poor prognosis. To reach this conclusion, we analyzed patient samples of individuals treated with oxaliplatin from the GSE83129 dataset, and a set of datasets validated using ROCplotter, selecting them based on their response to the drug. By analyzing multiple oxaliplatin-resistant and -sensitive cell lines, we identified oxidative phosphorylation KEGG pathways as a valuable predictive biomarker of oxaliplatin response with a high area under the curve (AUC = 0.843). Additionally, some oxidative phosphorylation-related biomarkers were validated in primary- and metastatic-derived tumorspheres, confirming the results obtained in silico. The low expression of these biomarkers is clinically relevant, indicating poor prognosis with decreased overall and relapse-free survival. This study proposes using oxidative phosphorylation-related protein expression levels as a predictor of responses to oxaliplatin-based treatments to prevent relapse and enable a more personalized therapy approach. Our results underscore the value of oxidative phosphorylation as a reliable marker for predicting the response to oxaliplatin treatment in colorectal cancer.

This work proposes a high-efficiency High-Brightness LED (HB-LED) driver for Visible Light Communication (VLC) based on a Two-Input Buck (TIBuck) DC/DC converter. This solution not only outperforms previous approaches based on Buck DC/DC converters, but also simplifies previous proposals for VLC drivers that use the split power technique with two DC/DC converters: one is in charge of the communication tasks and the other controls the biasing of the HB-LED (i.e., lighting tasks). The real implementation of this scheme requires either two input voltage sources, one of which is isolated, or one DC/DC converter with galvanic isolation. The proposed implementation of splitting the power is based on a TIBuck DC/DC converter that avoids the isolation requirement, overcoming the major drawback of this technique, keeping high-efficiency and high communication capability thanks to the lower voltage stress both across the switches and at the switching node. This fact allows for the operation at very high frequency for communication purposes, minimizing switching power losses, achieving high efficiency and providing lower filtering effort. Moreover, the duty ratio range can also be adapted to the useful voltage range of the HB-LED load to maximize the resolution on the tracking of the output volage. The power is split by means of an auxiliary Buck DC/DC converter operating at low switching frequency, which generates the secondary voltage source needed by the TIBuck DC/DC converter. This defines a natural split of power by only processing the power delivered for communications purposes at high frequency. A 7 W output-power experimental prototype of the proposed VLC driver was built and tested. Based on the experimental results, the prototype achieved 94% efficiency, reproducing a 64-QAM digital modulation scheme and achieving a bit rate of 1.5 Mbps with error in communication of 12%.

Staphylococcus aureus is an opportunistic pathogen and a leading cause of bloodstream infections, with its capacity to acquire antibiotic resistance genes posing significant treatment challenges. This pilot study characterizes the genomic profiles of S. aureus isolates from patients with bloodstream infections in KwaZulu-Natal, South Africa, to gain insights into their resistance mechanisms, virulence factors, and clonal and phylogenetic relationships. Six multidrug-resistant (MDR) S. aureus isolates, comprising three methicillin-resistant S. aureus (MRSA) and three methicillin-susceptible S. aureus (MSSA), underwent whole genome sequencing and bioinformatics analysis. These isolates carried a range of resistance genes, including blaZ, aac(6′)-aph(2″), ant(9)-Ia, ant(6)-Ia, and fosB. The mecA gene, which confers methicillin resistance, was detected only in MRSA strains. The isolates exhibited six distinct spa types (t9475, t355, t045, t1265, t1257, and t7888) and varied in virulence gene profiles. Panton–Valentine leukocidin (Luk-PV) was found in one MSSA isolate. Two SCCmec types, IVd(2B) and I(1B), were identified, and the isolates were classified into four multilocus sequence types (MLSTs), with ST5 (n = 3) being the most common. These sequence types clustered into two clonal complexes, CC5 and CC8. Notably, two MRSA clones were identified: ST5-CC5-t045-SCCmec_I(1B) and the human-associated endemic clone ST612-CC8-t1257-SCCmec_IVd(2B). Phylogenomic analysis revealed clustering by MLST, indicating strong genetic relationships within clonal complexes. These findings highlight the value of genomic surveillance in guiding targeted interventions to reduce treatment failures and mortality.

The use of biochar in water resource and recovery facilities (WRRF) shows promise for recovery of phosphorus (P) to use as a biochar-based fertilizer (BBF) that can replace conventional fertilizers, promote carbon sequestration, and improve soil quality. In this study, biochar was recovered after being dosed into secondary-treated discharge from a municipal WRRF. The value of the recovered biochar as a BBF was tested in a lettuce (Lactuca sativa) growth trial. The BBF was compared to an inorganic fertilizer, raw biochar, and controls that had either only nitrogen (N) fertilizer or no amendment. The ability of the treatments to support plant growth was determined by measuring plant height, biomass, leaf tissue total N and P concentration, and plant quality. Plant quality for the Fe-modified biochar used in the WRRF was 9.05 (±0.44) on a 10-point scale compared to 9.61 (±0.46) for the inorganic fertilizer treatment and 2.22 (±0.82) for the untreated control. Plant tissue P concentrations were 6.28 (±0.83), 9.88 (±0.90), 15.46 (±2.54), and 6.36 (±1.91) g plant−1 for the raw biochar, Fe-modified biochar used in the WRRF, inorganic fertilizer, and no amendment treatments, respectively. Soil P availability and P uptake amount in the leaves indicated that the BBF released P more slowly than the inorganic P fertilizer; however, it was sufficiently available for uptake to support plant growth to maturity. Results from these experiments show that Fe-modified biochar used in WRRF can supply adequate P to plants. The slow release will reduce P leaching into surface waters.

Abstract Lignocellulosic biomass represents a carbon neutral cheap and versatile source of carbon which can be converted to biofuels. A pretreatment step is frequently used to make the lignocellulosic carbon bioavailable for microbial metabolism. Dilute acid pretreatment at high temperature and pressure is commonly utilized to efficiently solubilize the pentose fraction by hydrolyzing the hemicellulose fibers and the process results in formation of furans—furfural and 5-hydroxymethyl furfural—and other inhibitors which are detrimental to metabolism. The presence of inhibitors in the medium reduce productivity of microbial biocatalysts and result in increased production costs. Furfural is the key furan inhibitor which acts synergistically along with other inhibitors present in the hydrolysate. In this review, the mode of furfural toxicity on microbial metabolism and metabolic strategies to increase tolerance is discussed. Shared cellular targets between furfural and acetic acid are compared followed by discussing further strategies to engineer tolerance. Finally, the possibility to use furfural as a model inhibitor of dilute acid pretreated lignocellulosic hydrolysate is discussed. The furfural tolerant strains will harbor an efficient lignocellulosic carbon to pyruvate conversion mechanism in presence of stressors in the medium. The pyruvate can be channeled to any metabolite of interest by appropriate modulation of downstream pathway of interest. The aim of this review is to emphasize the use of hydrolysate as a carbon source for bioproduction of biofuels and other compounds of industrial importance.

Abstract Objective Lung cancer is the second most frequent cancer type and the most common cause of cancer-related deaths worldwide. Alteration of gene copy numbers are associated with lung cancer and the determination of copy number variations (CNV) is appropriate for the discrimination between tumor and non-tumor tissue in lung cancer. As telomerase reverse transcriptase (TERT) and v-myc avian myelocytomatosis viral oncogene homolog (MYC) play a role in lung cancer the aims of this study were the verification of our recent results analyzing MYC CNV in tumor and non-tumor tissue of lung cancer patients using an independent study group and the assessment of TERT CNV as an additional marker. Results TERT and MYC status was analyzed using digital PCR (dPCR) in tumor and adjacent non-tumor tissue samples of 114 lung cancer patients. The difference between tumor and non-tumor samples were statistically significant (p

In the current scenario of fast technological advancement, increasingly characterized by widespread adoption of Artificial Intelligence (AI)-driven tools, the significance of autonomous systems like chatbots has been highlighted. Such systems, which are proficient in addressing queries based on PDF files, hold the potential to revolutionize customer support and post-sales services in the automotive sector, resulting in time and resource optimization. Within this scenario, this work explores the adoption of Large Language Models (LLMs) to create AI-assisted tools for the automotive sector, assuming three distinct methods for comparative analysis. For them, broad assessment criteria are considered in order to encompass response accuracy, cost, and user experience. The achieved results demonstrate that the choice of the most adequate method in this context hinges on the selected criteria, with different practical implications. Therefore, this work provides insights into the effectiveness and applicability of chatbots in the automotive industry, particularly when interfacing with automotive manuals, facilitating the implementation of productive generative AI strategies that meet the demands of the sector.

Primary central nervous system lymphoma (PCNSL) is primarily treated with combination chemotherapy, while whole-brain radiotherapy (WBRT) can be used as consolidative treatment or as a salvage option for central nervous system (CNS) relapse. We investigated whether fractionated stereotactic radiosurgery (fSRS) could replace WBRT in cases where patients had poor performance status or minimal disease at the time of consolidation, to spare patients the adverse effects of WBRT. We retrospectively identified 10 patients who completed 14 courses of fSRS for PCNSL or for CNS relapse of systemic lymphoma. Of 14 fSRS treatments, there were 10 distant brain recurrences among 6 patients, occurring on average 13.6 months after fSRS. A total of 4 of the 10 recurrences were treated with further fSRS, and 4 were treated with WBRT. There was one late in-field recurrence after both fSRS and WBRT, which occurred 27 months after fSRS. The median survival after fSRS was 36 months, and side effects after fSRS were minimal. This case series represents a potential treatment option for patients with CNS lymphoma, for whom WBRT is indicated but where the toxic effects of this treatment would be prohibitive.

Abstract Plant disease resistance genes are widely used in agriculture to reduce disease outbreaks and epidemics and ensure global food security. In soybean, Rps (Resistance to Phytophthora sojae) genes are used to manage Phytophthora sojae, a major oomycete pathogen that causes Phytophthora stem and root rot (PRR) worldwide. This study aims to identify temporal changes in P. sojae pathotype complexity, diversity, and Rps gene efficacy. Pathotype data was collected from 5121 isolates of P. sojae, derived from 29 surveys conducted between 1990 and 2019 across the United States, Argentina, Canada, and China. This systematic review shows a loss of efficacy of specific Rps genes utilized for disease management and a significant increase in the pathotype diversity of isolates over time. This study finds that the most widely deployed Rps genes used to manage PRR globally, Rps1a, Rps1c and Rps1k, are no longer effective for PRR management in the United States, Argentina, and Canada. This systematic review emphasizes the need to widely introduce new sources of resistance to P. sojae, such as Rps3a, Rps6, or Rps11, into commercial cultivars to effectively manage PRR going forward.

Abstract Clostridium thermocellum is a natively cellulolytic bacterium that is promising candidate for cellulosic biofuel production, and can produce ethanol at high yields (75–80% of theoretical) but the ethanol titers produced thus far are too low for commercial application. In several strains of C. thermocellum engineered for increased ethanol yield, ethanol titer seems to be limited by ethanol tolerance. Previous work to improve ethanol tolerance has focused on the WT organism. In this work, we focused on understanding ethanol tolerance in several engineered strains of C. thermocellum. We observed a tradeoff between ethanol tolerance and production. Adaptation for increased ethanol tolerance decreases ethanol production. Second, we observed a consistent genetic response to ethanol stress involving mutations at the AdhE locus. These mutations typically reduced NADH-linked ADH activity. About half of the ethanol tolerance phenotype could be attributed to the elimination of NADH-linked activity based on a targeted deletion of adhE. Finally, we observed that rich growth medium increases ethanol tolerance, but this effect is eliminated in an adhE deletion strain. Together, these suggest that ethanol inhibits growth and metabolism via a redox-imbalance mechanism. The improved understanding of mechanisms of ethanol tolerance described here lays a foundation for developing strains of C. thermocellum with improved ethanol production.

This article considers the process of optimizing the time and convenience of taking academic debts by creating a Telegram bot that automatically sends students notifications about debts and indicates the day when they can be passed. One of today’s popular platforms for deploying bots is the Telegram messenger. The peculiarity of a system implemented with the help of a bot is its ease of use and minimization of resources spent on software storage, which greatly simplifies interaction with the system. Purpose – create a tool for passing academic debts, interaction with the database created in Google Table, interaction with the participants of the educational process online, which saves personal time of students and teachers. Method or methodology of the work: the article deals with the method which implements the delivery of academic debts by creating Telegram bot. To implement it we use a database available to all teachers, updated in real time, created in Google Tables and the C# programming language. Result: developed a unique tool that implements functions of adding, storing, interacting and 24/7 access to academic debts data. Scope of the results: data on debts stored in the database and updated by teachers is useful for monitoring each student about his debts in educational institutions.