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The Carbon Budget of Agroecosystems in Relatin to Tillage and Nitrogen Fertilizer Management
No full textIUISoil organic carbon (SOC) is a crucial component of soil fertility and functionality. Agricultural intensification, particularly tillage and heavy nitrogen (N) fertilization, has led to SOC depletion in croplands, ultimately contributing to increased atmospheric CO₂ concentration. Adoption of no-till (NT) and balanced N management can boost plant productivity, increase crop residue input and improve soil structure, ultimately enhancing SOC storage and mitigating climate change. However, in some contexts, these benefits do not materialize due to concurrent increase in greenhouse gas (GHG) emissions, especially nitrous oxide (N2O), which can offset SOC gains. Few studies have systematically investigated the interactive effects of NT and N fertilization on SOC accumulation, SOC characteristics and GHG emission; thus, an important knowledge gap exists regarding the net impact of these agronomic interventions on the carbon (C) budget of agroecosystems. To address this gap, a comprehensive field and laboratory study was conducted using experimental plots (established in 1970 at the University of Kentucky) under continuous corn, managed with either moldboard plow (MB) or no-tillage (NT), and receiving N fertilizer at rates of 0, 84 and 168 kg N ha-1 y-1. Using soil ¹³C abundance and an isotope‐mixing model, corn-derived SOC sequestration was quantified and partitioned into labile particulate organic matter (POM-C) and stable mineral-associated organic matter (MAOM-C). Several thermal oxidation techniques, including differential scanning calorimetry and thermogravimetry, were used to assess SOC stability. Field-measured GHG fluxes were converted into CO₂-C equivalents and subtracted from the SOC sequestration rate to calculate the net C budget. Compared to MB, NT increased SOC stocks, retained more corn-derived C, and lowered GHG emissions, yielding a net C balance of 0.17-0.47 Mg C ha-1 y-1 (versus ~0.07 under MB). Data on MAOM formation and thermal oxidation also showed greater SOC stability under NT. These results underscore that NT, with a balanced N fertilization regime, is an effective strategy to enhance soil health and minimize the carbon footprint of agroecosystems
Bridging Neuroimaging and Pathology in Dementia: A Multi‐Cohort Investigation of MRI‐Derived Brain Volumes
No full textBackground:
The ability to precisely characterize neurodegenerative diseases at early stages remains a challenge. Understanding the relationship between magnetic resonance Imaging (MRI)‐derived brain volumes and neuropathological outcomes is key to advancing early and accurate diagnosis of neurodegenerative diseases. While MRI‐based volumetrics are widely used to assess structural changes in vivo, their link to neuropathological findings remains underexplored. This study examines associations between region‐specific brain atrophy and neuropathological markers, including Alzheimer's Disease Neuropathologic Change (ADNC), CERAD score, Braak staging, and Thal amyloid phase, leveraging volumetric data across multiple aging cohorts.
Method:
T1‐weighted MRI scans from participants in longitudinal dementia cohorts (ROS, MAP, MARS, and NACC) were pre‐processed, and brain volumes of 120 cerebral regions of interest (ROIs) were calculated using Multi‐Atlas Segmentation Utilizing Ensembles (MUSE). Associations between ROI volumes and neuropathological metrics were analysed using linear regression, adjusting for age at scan, difference between age at death and age at scan, sex, intracranial volume, and site/scanner. Neuropathological metrics, including ADNC, CERAD scores, Thal phase, Braak staging, and vascular metrics like atherosclerosis were analysed as continuous variables grouped categorically (e.g., Thal phase recoded into three categories: 0, 1, and 2). Statistical significance was determined using Benjamini‐Hochberg method (p <0.05).
Result:
Among 755 participants (mean age at scan: 80.57±10.23 years; mean age at death: 85.49±10.45 years; 44% male), ADNC was associated with atrophy in temporal and parietal regions, notably middle and inferior temporal gyri, angular gyrus, and amygdala. CERAD scores correlated with atrophy in middle temporal, para‐hippocampal, and fusiform gyrus, Thal phase with atrophy in middle temporal, angular gyrus, and precuneus and Braak staging showed atrophy in entorhinal cortex, middle temporal gyrus, and para‐hippocampal regions. Atherosclerosis was associated with atrophy in prefrontal cortex, and parieto‐occipital regions.
Conclusion:
These findings highlight the potential of MRI‐derived volumetrics as non‐invasive biomarkers of underlying Alzheimer's pathology. Our findings demonstrate notable atrophy in medial temporal, lateral temporoparietal, and midline parietal regions, supporting recognized AD patterns of neurodegeneration, consistent with pivotal studies by Habes et al.,(2016), Dickerson et al.,(2009). Associations between amyloid, tau burdens and atrophy in temporal, parietal, and limbic regions underscore their diagnostic value in neurodegeneration
Functional connectivity network identifiability across a multi‐year follow‐up in the Korean Brain Aging Study for the Early Diagnosis and Prediction of AD
No full textBackground:
Resting state functional magnetic resonance imaging (rsfMRI) is a promising potential biomarker for diagnostic and prognostic assessment in Alzheimer's disease (AD) as it provides spatial and temporal information on brain functional connectivity (FC). The protracted course of AD necessitates a better understanding of the longitudinal utility of FC. Therefore, we utilized FC identifiability (ability to match scans at different visits from the same patient) to investigate whether participants with varying diagnostic AD severity displayed differential identifiability over two‐ and four‐year follow‐ups.
Method:
KBASE rsfMRI data from 70 younger and 284 older cognitively normal (yCN, mean age: 38±9.8yo and oCN, 69±8yo), 147 mild cognitive impairment (MCI, 73.5±6.9yo), and 87 AD dementia (72.5±7.8yo) participants at baseline, underwent standard preprocessing and nuisance regression to generate Pearson correlation FC networks with the Schaefer 200 cortical region functional parcellation. Identifiability (the correlation between FC connections (edges) for any scan pair) was computed within visit (baseline: n = 594, 2‐year: n = 371, 4‐year: n = 207) and across visit pairs (baseline‐2year: n = 369, baseline‐4year: n = 207, 2year‐4year: n = 181), where participants were further stratified based on visit‐to‐visit change in diagnosis. Measures of interest were self‐identifiability (Iself), mean identifiability to others (Iothers), and differential identifiability defined as the proportion of Iself>Iothers.
Result:
Cross‐sectional identifiability at diagnostic group average showed a reduction in AD versus the oCN and MCI groups, white participant level matrices showed variability both within and between diagnostic groups (Figure 1). Longitudinal identifiability recapitulated this variability, while showing that a large portion of participants can be matched based on FC at two and four years apart (Figure 2). Success rate of identifiability was >80% for vast majority oCN participants and was reduced and more variable in diagnostic MCI/AD groups (Figure 3).
Conclusion:
The observed variability in identifiability recapitulates prior knowledge in the field at a 2‐year gap, extending for the first time to a 4‐year gap. The variable differential identifiability success rates in diagnostic groups necessitates further investigations into contributing patient specific factors, as explaining this variance is key in furthering the clinical utility of FC in AD
Reproducibility and Diagnostic Utility of a Simplified Oil Red O Test in Infant Bronchoalveolar Lavage Samples
No full textIntroduction: Aspiration in infants is a diagnostic challenge. The lipid-laden macrophage index (LLMI) developed in 1987 has been used as a supportive test; however, numerous recent studies have questioned its value and reproducibility. We evaluated a simplified LLMI in bronchoalveolar lavage (BAL) specimens from a pediatric cohort to assess its diagnostic utility.
Methods: BALs from infants were prospectively collected over a 6-month period for Oil Red O (ORO) staining to evaluate aspiration. BALs from adults with non-aspiration pathologies were simultaneously collected for comparison. Clinical and demographic data were gathered to assess the diagnostic accuracy of the test. Only samples containing ≥ 100 evaluable macrophages and free of obscuring blood or inflammation were included. Positive staining was assessed at low magnification (10×), with only clearly positive cells (Colombo-Hallberg scores 3 and 4) considered. A dichotomous threshold of < 50% or ≥ 50% positive macrophages was established through multidisciplinary consensus. To ensure consistency, a training session was conducted for the entire cytopathology division on the newly developed interpretation criteria.
Results: 88/134 (66%) pediatric BAL samples with suspected aspiration and 63/75 (84%) adult samples with various non-aspiration pathologies were adequate for analysis. Aspiration status in children was determined using multidisciplinary aerodigestive group evaluation (MAGE) and videofluoroscopic swallow study (VFSS). Test performance was assessed at various cutoffs. In the pediatric cohort (mean age 16.5 months, 58% male), aspiration was diagnosed in 47% by MAGE. Strong associations were seen with atopia/asthma (83%), functional dysphagia (64%), and congenital/developmental disorders (43%). A significant difference in ≥ 50% lipid-laden macrophage involvement was observed between pediatric (12%) and adult (51%) samples (p < 0.00001). Using MAGE and VFSS as gold standards, the test showed poor discriminatory power for detecting aspiration in infants (AUC 0.506-0.587). A 10% cutoff yielded the best performance (AUC 0.587, sensitivity 27%, specificity 93%), while a 50% cutoff offered practical advantages in workflow and reproducibility.
Conclusions: The modified LLMI demonstrates limited diagnostic value for aspiration in infants. While a 10% cutoff offers slightly improved performance, the test may be phased out in favor of more reliable diagnostic methods
A phase I study targeting the APE1/Ref-1 redox signaling protein with APX3330: first clinical agent targeting APE1/Ref-1 in cancer
No full textBackground: APX3330 is an oral agent targeting the redox signaling activity of APE1/Ref-1 (Ref-1), a key regulator of transcription factors involved in inflammation and tumorigenesis. APX3330 selectively inhibits Ref-1's redox function without affecting its DNA repair role. This Phase 1, multicenter, open-label, dose-escalation study in advanced solid tumors was aimed at determining the recommended Phase 2 dose (RP2D) while assessing safety, pharmacokinetics, and biomarker evidence of target engagement.
Methods: Nineteen cancer patients were treated, with eight completing follow-ups. Subjects received APX3330 orally twice daily in 21-day cycles, starting at 240 mg/d and escalating in 120 mg/d increments. Adverse event (AE) monitoring followed a 1 pt/cohort approach until a >G2 toxicity event, after which a 3 + 3 design was implemented. Treatment continued until disease progression, consent withdrawal, or intolerable toxicity. Antitumor activity was assessed using RECIST 1.1, and pharmacodynamic markers included serum Ref-1 levels and circulating tumor cells.
Results: Six of nineteen subjects had stable disease, and no treatment-related SAEs were observed. One subject (720 mg cohort) withdrew due to Grade 3 maculopapular rash (dose-limiting toxicity). Laboratory assessments and ECGs showed no clinically significant abnormalities.
Conclusions: APX3330 showed preliminary signals of disease control and on-target pharmacology in this first-in-human study. Based on safety and PD, the RP2D is 600 mg/d. Given the small sample size, efficacy conclusions are exploratory
Cognitive data harmonization in the ADRC Network and beyond-Past, present, and future
No full textThe National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) includes extensive cognitive data contributed by Alzheimer's Disease Research Centers (ADRCs) since 2005. The UDS has evolved over time and is on its fourth iteration. In addition to this core dataset, individual ADRCs have administered augmented neuropsychological batteries to research participants that go beyond the UDS. Here we describe ongoing efforts and future plans to optimize use of these data with modern psychometric methods. Modern psychometric methods address challenges from an evolving battery of cognitive tests. To date, most efforts using modern psychometric methods have focused on harmonization and co-calibration of ADRCs' UDS and non-UDS cognitive data, while recent efforts address additional areas such as subjective cognitive impairment. Modern psychometric methods provide a workable framework for anticipated future developments, including digital cognitive testing and analyses of spoken responses. These methods facilitate optimal use of NACC's data riches to further its mission to facilitate collaborative research. HIGHLIGHTS: National Alzheimer's Coordinating Center (NACC) data collection includes an extensive cognitive battery that has changed over time. An ambitious project has harmonized and co-calibrated cognitive domain scores for memory, executive functioning, and language. Scores and their standard errors are available from the NACC. Those scores are co-calibrated with domain scores from many additional studies, facilitating cross-study scientific investigation. Future opportunities include digital data collection, consideration of neuropsychiatric symptoms and subjective cognitive impairment, and other uses of the granular cognitive data
Treatment‐related changes in the prostate: past, present and future therapies
No full textA broad spectrum of therapies is available for the management of prostate cancer, ranging from well-established interventions like radical prostatectomy, androgen deprivation therapy (ADT) and radiation therapy (RT), to emerging modalities such as focal ablative treatments and targeted molecular therapies. These therapies can induce profound histologic alterations in both benign and malignant prostate tissue. Hormonal and radiation therapies are particularly known for their distinctive and often extensive morphologic effects, which have been well documented across needle biopsies, transurethral resection of the prostate (TURP) or enucleation specimens and prostatectomy samples. Novel ablative techniques-including cryotherapy, high-intensity focused ultrasound (HIFU), photodynamic therapy (PDT) and interstitial laser thermotherapy-are gaining traction, yet the histologic consequences of these newer modalities are still being characterized. These treatment-induced changes can obscure residual carcinoma, complicate tumour grading and staging and sometimes render traditional parameters such as Gleason scoring unreliable. As therapies evolve, pathologists must remain informed about the spectrum of post-treatment changes to accurately interpret prostate specimens. Diagnostic accuracy hinges not only on recognizing these morphologic effects but also on integrating clinical history, particularly when treatment details are not readily available. This review provides an overview of current and investigational prostate cancer therapies, their histologic impact and practical guidance for post-treatment evaluation
Indiana's 2024 Behavioral Health and Human Services Workforce Snapshot: Licensed Clinical Addiction Counselors
No full textThis document is a 2024 data snapshot of actively practicing Licensed Clinical Addiction Counselors (LCACs) in Indiana within the Behavioral Health and Human Services workforce. It reports a small active workforce (178 LCACs) and identifies primary practice settings, with most practicing in specialized substance abuse outpatient treatment facilities, followed by private practice and community mental health centers. The document highlights core services provided, primarily addiction counseling, often delivered through telehealth, and identifies key populations served, with a strong emphasis on adults and individuals in recovery
Domain-General Neural Effects of Associative Learning and Expectations on Pain and Hedonic Taste Perception
No full textPredictive cues significantly influence perception through associative learning. However, it is unknown whether circuits are conserved across domains. We investigated how associative learning influences perceived intensity and valence of pain and hedonic taste and whether expectancy-based modulation varies by aversiveness or modality. Sixty participants (37 females, 23 males) were randomly assigned to receive either painful heat, unpleasant liquid saline, or pleasant liquid sucrose during fMRI scanning. Following conditioning, cues initially associated with low- or high-intensity outcomes were intermittently followed by stimuli calibrated to elicit medium-intensity ratings. Learned cues modulated expectations and subjective outcomes similarly across domains. Consistent with this, the orbitofrontal cortex exhibited domain-general anticipatory activation. Cue effects on perceived intensity and valence were mediated by the left anterior insula and thalamus, respectively-regions closely overlapping those identified in prior studies of pain expectancy (Atlas et al., 2010). Pain specificity was evident when we measured variations in stimulus intensity, whether we used univariate or multivariate approaches, but there was minimal evidence of specificity by modality or aversiveness in cue effects on medium trials. These findings suggest that shared neural circuits mediate the effects of learned expectations on perception, linking pain with other areas of affective processing and perception across domains
Pseudopheochromocytoma With Catecholamine Excess and End-organ Damage: A 30-year Course Treated With Escitalopram
No full textPseudopheochromocytoma is a disorder characterized by paroxysmal hypertension and variably elevated catecholamine metabolite levels. Pseudopheochromocytoma clinically mimics pheochromocytoma but differs in etiology. While pheochromocytoma is a catecholamine-secreting neuroendocrine tumor, pseudopheochromocytoma is a syndrome linked to a history of emotional stressors and is believed to stem from autonomic nervous system dysregulation. We present the case of a 70-year-old female patient experiencing episodic hypertensive crises for 3 decades. The patient was referred to endocrine oncology for evaluation of a possible pheochromocytoma due to her long-standing history of symptomatic hypertension and elevated catecholamine metabolites. Anatomic and functional imaging, including computed tomography scans of the abdomen and pelvis and a 64Copper-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-octreotate positron emission tomography computed tomography excluded a diagnosis of pheochromocytoma or paraganglioma. Her history of significant emotional stressors raised the possibility of pseudopheochromocytoma. Following initiation of escitalopram and psychotherapy, the patient experienced a remarkable improvement in the frequency and severity of hypertensive episodes. This case illustrates the diagnostic challenges of pseudopheochromocytoma and the importance of early intervention in preventing complications