bluuebunny/crossref_metadata_2025 huggingface dataset:
LGI1 encephalitis manifesting as a delayed paraneoplastic response of squamous cell lung cancer on remission
Authors: Chukwuocha Ikechukwu , Al-Moyeed Baig , Eigbe Solomon , Shukla Shilpi
Published: December 2024

The leucine-rich glioma-inactivated protein 1 (LGI1) antibody-related autoimmune encephalitis can occur alone or in the setting of a malignancy and manifest with faciobrachial dystonic seizures (FBDS), cognitive decline, hyponatremia, and neuropsychiatric disorders. The importance of differentiating this entity from acute delirium cannot be overemphasized.

This review provides a detailed account of a 71-year-old man with previous diagnosis of lung cancer who presented with subacute onset behavioural changes, urinary retention, and FBDS. Investigation revealed hyponatremia, bilateral mesial temporal lobe high signal abnormality worse on the right on MRI and CSF positive anti-LGI1 antibodies (1:30). The patient was treated with immunosuppressive therapy with consequent symptom improvement.

This case emphasizes the need to have a high index of suspicion for this disease entity in patients presenting with new onset behavioural changes and the importance of identifying the typical FBDS, as early initiation of treatment confers a positive outcome for diseased patients.
Analyses of radioactivity concentrations in soil and assessment of effective doses in several districts of Banten and West Java, Indonesia
Authors: Makhsun  , Iskandar Dadong , Wahyudi  , Nugraha Eka Djatnika
Published: December 2024

Radioactivity concentration in soil was analyzed around the capital city of Indonesia, Jakarta along with the adjoining provinces of West Java and Banten, representing one of the most densely populated in Indonesia. Nestled within this area is a nuclear research reactor. The analysis of natural and artificial radioactivity concentrations using a HPGe gamma spectrometry to measure 226Ra, 232Th, 40K, and 137Cs in surface soil samples. The results indicate that the average activity concentrations of 226Ra, 232Th, and 40K ranged from 18 to 49, 24 to 74, and 18 to 249 Bq/kg, respectively. The calculated value for the total average absorbed dose rate in the air in Banten and West Java is 38 ± 4 and 34 ± 4 nGy/h. Nonetheless, the calculated value of the external hazard index indicates that the soils in that region are deemed suitable for use in construction materials, and the area is safe for habitation. The activity concentrations of 137Cs in several districts of Banten and West Java ranged from <0.09 to 0.73 Bq/kg. Even a minor introduction of artificial radioactivity into the environment constitutes a form of pollution that must be closely monitored as a potential environmental threat.
Increasing Premedication for Neonatal Intubation: A Quality Improvement Initiative
Authors: Lucena Michelle H. , Morgan-Joseph Toshiba , Thompson-Branch Alecia
Published: December 2024

Introduction:

Endotracheal intubation is frequent in the neonatal intensive care unit (NICU) but may result in neonatal distress and instability. Premedication reduces adverse effects, such as hypoxia, bradycardia, and pain. The Specific, Measurable, Achievable, Relevant and Time-Bound aim for this project was to increase premedication use for nonemergent neonatal intubation in a specific NICU from 22% to 80% from March 2021 to May 2023.

Methods:

We use quality improvement methodology to explain our theory for improvement. Our key driver diagram depicts this initiative’s aims, key drivers, and interventions to increase premedication use for neonatal intubation. We defined exclusion criteria and medications, and one author collected demographic data retrospectively after the procedure. The stakeholders summarized the baseline data, performed plan-do-study-act cycles, and showed outcome measures in a statistical process control chart. Statistical analysis used Fisher’s exact test to compare categorical variables.

Results:

Between 2021 and 2023, 333 infants underwent endotracheal intubation; 130 infants were included. The most common indication for intubation was hypoxemic respiratory failure—52% (68/130). Premedication use increased from 22% to 52%. Among the exclusion criteria, the most common indication for nonpremedication was intubation in the delivery room, 38.4% (78/203). In the premedication group, intubation on the first attempt occurred in 77.6% (52/67) of the cases, versus the nonpremedication group, 66.7% (32/48) (P = 0.3).

Conclusions:

Premedication for neonatal intubation increased by 30%, although we did not reach the desired 80% goal. Establishing a premedication bundle, alongside a unit-specific protocol and effective teamwork, marks the initial stride toward enhancing analgesia/sedation practices in the NICU.
Reducing Sedation for Pediatric Thoracic CT Imaging Using Volumetric Target-mode EKG Gating
Authors: Shah Summit H. , Young Cody M. , Morrison Jessica , Chmil Margarita , Ruess Lynne , Krishnamurthy Rajesh
Published: December 2024

Introduction:

Many children require sedation for imaging. We aimed to reduce sedation for thoracic (chest and cardiac) computed tomography (CT) scans in children 0–4 years old from 65% to 20% by December 2018 and to sustain.

Methods:

We counted baseline, intervention, and a follow-up period thoracic CT scans performed with sedation in children 0–4 years old. We developed a new volumetric target-mode electrocardiogram-gated CT imaging protocol to reduce scan time and control for factors that decrease image quality. Additional interventions included technologist training, communication to radiologists and clinicians, and eliminating a default request for sedation accompanying the electronic order for most thoracic CT scans. A statistical process control chart tracked data to study process changes over time.

Results:

During the baseline and intervention periods, 232 of 357 and 217 of 794 scans required sedation. Interventions created 2 centerline shifts. Overall, thoracic CT scans in children 0–4 years old requiring sedation decreased from 65% to 24% and was sustained 5 years later. No patients during the baseline period, one (1 of 794, 0.1%) during the intervention period and 2 (2 of 480, 0.4%) during the audit period 5 years later, initially had nondiagnostic nonsedated scans that required an additional scan with sedation.

Conclusions:

We developed a volumetric target-mode electrocardiogram-gated CT protocol, eliminated default sedation ordering, and trained and educated staff to reduce sedation in young children undergoing thoracic CT scans. The frequency of sedation for thoracic CT in children 0–4 years old decreased from 65% to 24% and was sustained after revising imaging parameters and eliminating a default sedation order.
Small fiber pathology in fibromyalgia syndrome
Authors: Sommer Claudia , Üçeyler Nurcan
Published: December 2024

About 50% of women with fibromyalgia syndrome have reduced skin innervation. This finding is consistent in patient cohorts from different regions of the world. Small fiber function may also be affected, as shown by various studies using different methods, such as quantitative sensory testing or special small fiber neurophysiology such as C-fiber microneurography. Microneurography in particular has shown increased spontaneous activity, mechanosensitivity, and enhanced activity-induced slowing in C fibers of patients with fibromyalgia. Generalized reduction of skin innervation, ie, proximally and distally, was associated with higher symptom severity and more pronounced central nervous system changes as seen in magnetic resonance tomography. The question whether peripheral or central nervous system changes come first, or whether both are signs of an underlying pathology, has not been resolved yet. For clinical practice, it is important to note that reduced skin innervation in fibromyalgia must not be confused with small fiber neuropathy, which is a separate entity with different characteristics and pathophysiology. Further prospective research is warranted to transfer these findings in the peripheral nervous system into clinical fibromyalgia patient management.
Applying evidence-based cross-disciplinary concepts helps to explain the heterogeneity in pain, function, and biological measures in individuals with knee pain with/at risk of osteoarthritis
Authors: Mickle Angela M. , Tanner Jared J. , Holmes Udell , Rashid Ahmed , Barolette Olivier , Addison Brittany , Sambuco Nicola , Garvan Cynthia , Lai Song , Seubert Christoph , Schmidt Siegfried , Staud Roland , Edberg Jeffrey C. , Redden David , Goodin Burel R. , Price Catherine C. , Fillingim Roger B. , Sibille Kimberly T.
Published: December 2024

Introduction:

Factors contributing to individual differences in knee osteoarthritis remain elusive. Dispositional traits and socioeconomic status are independent predictors of mental and physical health, although significant variability remains. Dispositional traits serve as the biological interface for life experiences.

Objectives:

We investigate group differences based on dispositional traits and poverty status, specific to (1) pain intensity and functional limitations and (2) biological measures, a clinical composite and brain age.

Methods:

Adults aged 45 to 85 years with knee pain associated with chronic musculoskeletal pain provided information on demographics, socioeconomic and psychosocial factors, pain, and physical function. Kellgren–Lawrence scores were determined from knee radiographs, the clinical composite from fasting blood draws, and brain age from MRI data.

Results:

One hundred seventy-three individuals participated in the study. Of those, 117 had protective dispositional traits (81 above poverty/36 in poverty), and 56 had vulnerable dispositional traits (24 above poverty/32 in poverty). With sex, study site, Kellgren–Lawrence score, and age/or image quality as covariates, significant group differences were observed across clinical pain (P < 0.001), functional limitations (P ≤ 0.001), and brain age (P ≤ 0.002) measures. Although not significant, the clinical composite measure aligned with the other outcome measures and demonstrated the hormesis inverted U pattern.

Conclusions:

Groups based on dispositional traits and socioeconomic status explain differing clinical outcomes. Consistent with the allostatic load and hormesis inverted U models, one group was in an adaptive health status, 2 groups were showing signs of developing load, and the fourth group showing signs of overload, at risk of worse health outcomes.
APHIX: Analysis Pipeline for HIV-1 Isoform eXploration Using Long-read RNA Sequencing Data
Authors: Albert Jessica L , Gallardo Christian M , Torbett Bruce E
Published: December 2024

HIV-1 uses 4 major splice donors and 8 major splice acceptors as well as dozens of minor, cryptic, and uncharacterized splice sites to produce over one hundred distinct transcript isoforms from a single 9.2 kb genome. As a result, existing bioinformatic pipelines struggle to accurately analyze spliced HIV sequences due to the complex nature of HIV alternative splicing compared to human mRNA splicing. Previous approaches to identify HIV isoforms from long-read sequencing data used pipelines that are not publicly available, are convoluted to operate, or are locked into a specific HIV strain, which limits their wide adoption to other experimental designs or systems. To address this gap, we have developed a bioinformatic pipeline calledAPHIXthat fully automates spliced isoform assignment, splice site usage quantification, and non-coding exon detection. APHIX takes a FASTQ/A of long-read transcripts and a HIV genome reference sequence and fully automates HIV isoform analysis. APHIX calculates splice site usage counts and percentages for each donor and acceptor site and their pairwise combinations, accurately assigns isoforms, and automatically identifies transcripts containing non-coding exons. APHIX is compatible with long-reads sequences generated from multiple platforms and library preps, including direct DNA and RNA sequencing. APHIX can also be adapted to multiple HIV-1 clades and strains by providing the appropriate reference sequence during bioinformatic processing. Overall, APHIX enables comprehensive processing of spliced sequences with reproducible results in a manner that is faster and easier to run compared to other methods.
Liver Radioembolization: Predicting Lung Shunt Fraction with Contrast-Enhanced CT, Eliminating the Need for 99mTc-MAA
Authors: Mehadji Brahim , Marx Talia , Carter Adrianna , Goldman Roger , Vu Catherine , Roncali Emilie
Published: December 2024

1.

Accurate estimation of the Lung Shunt Fraction (LSF) is a standard of care in yttrium-90 (90Y) radioembolization treatment planning to prevent excessive lung irradiation due to arterio-venous shunting in the liver. LSF is assessed using99mTc macroaggregated albumin (99mTc-MAA) imaging, but this approach adds risk, complexity, and expense to the treatment planning. This study investigates the potential of Contrast-Enhanced Computed Tomography (CECT) as a non-invasive alternative for LSF estimation.

Methods

We developed a novel metric to estimate the LSF from differences between CECT phases, based on the premise that LSF results from tumor angiogenesis and arterio-venous shunting that create excessive local opacity in the CECT arterial phase. Hypervascular volumes were identified by subtracting the portal phase from the arterial phase and contouring the corresponding regions using an density threshold. The perfused volume corresponded to the lobe and to the volume injected with99mTc-MAA.

We conducted a retrospective analysis involving 30 liver cancer patients who underwent 4-phase liver CECT and99mTc-MAA imaging prior to90Y radioembolization to study several markers based on the subtraction images. The patient cohort included several types of liver tumors (primary or metastatic), predominantly hepatocellular carcinoma. Correlations between the hypervascular-to-perfused volume ratio from CECT and LSF values from standard-of-care99mTc-MAA planar imaging were assessed.

Results

The strongest correlation was obtained between the hypervascular-to-perfused volume ratio from CECT and LSF values from99mTc-MAA planar gamma imaging (R²=0.95). The best correlation was demonstrated when the hypervascular volume was corrected by the hypoxic volume and then normalized by the perfused volume. In contrast, the tumor volume did not show a strong correlation with LSF (R²=0.38). Moreover, the predictive power of the hypervascular-to-perfused volume ratio on LSF demonstrated a 1-sigma uncertainty of 3%.

Conclusion

CECT-based LSF estimation shows promise as a non-invasive alternative to99mTc-MAA imaging in90Y treatment planning. Further validation with prospective studies on larger cohorts is necessary to confirm the accuracy and safety of this approach.
A STUDY TO ASSESS THE KNOWLEDGE AND ATTITUDE REGARDING OPTIONAL VACCINES AND BARRIERS TO USE AMONG MOTHERS OF UNDER FIVE CHILDREN IN KHEDA GUJARAT
Authors: Parmar Sherin , Dave Shlok , Vankar Sneha , Selot Srusti , Dabhi Sejal , Nagar Kailash
Published: December 2024

Introduction

Vaccination is a straightforward and reliable method to safeguard oneself from dangerous diseases before encountering them. Vaccination remains one of the most effective public health interventions in human history, significantly reducing the burden of infectious diseases and saving countless lives worldwide.

Aim

To determine knowledge and attitude regarding optional vaccines and barriers to use among mothers of under five children in Kheda district

Methodology

The non-experimental Descriptive Survey Research design used for this study. The study was conducted on 384 mothers of under five children from selected areas of Kheda district by systematic random sampling technique. A knowledge questionnaire tool, Likert attitude scale and barrier questionnaire was used for data collection.

Result

240 (63%) of mothers have low knowledge, 123 (32%) have moderate knowledge, and 21 (5%) have good knowledge regarding optional vaccination. When 1 (0.3%) mother have Unfavourable attitude, 275 (71.6%) have moderate attitude, and 108 (28.1%) have favourable attitude towards optional vaccination. The mean score of attitude is 8.7083. The Correlation-Coefficient (r) of knowledge and attitude is 0.76.

Conclusion

The study highlights the disparity between knowledge and attitude regarding optional vaccination among mothers of under five children. Although the majority lack adequate knowledge, a considerable number still maintain a moderate attitude. This emphasizes the need for targeted interventions to improve understanding and promote positive attitudes toward optional vaccination.
Subtypes of Older Adults Starting Long-Term Care in Japan: Unsupervised Machine Learning Approach
Authors: Hamasaki Yoko , Iwagami Masao , Komiyama Jun , Ito Yuji , Taniguchi Yuta , Inokuchi Ryota , Watanabe Taeko , Goto Tadahiro , Kuroda Naoaki , Suzuki Ai , Yoshie Satoru , Ishizaki Tatsuro , Iijima Katsuya , Tamiya Nanako
Published: December 2024

Objectives

The older population requiring long-term care (LTC) exhibits heterogeneity in physical and cognitive functions; however, an established classification is lacking. We aimed to identify distinct subgroups of older adults with LTC needs using unsupervised machine learning and to examine differences in their prognoses.

Design

Retrospective cohort study.

Setting and participants

Using survey data for care-need certification (linked to LTC and medical insurance claims) in City A, Japan, we identified community-dwelling adults aged ≥ 65 years who started LTC. Data from City B were used for validation of clustering.

Methods

We applied latent class analysis to group the participants in City A, based on all 74 items (38 on physical functions, 9 on cognitive functions, 15 on behavioral problems, and 12 on medical procedures) in the Japanese standardized care-needs certification survey. Then, we examined the association between the identified subtypes and four outcomes, including death, hospitalization, nursing home admission, and care-need level deterioration, using regression models.

Results

Among 3,841 participants in City A (median age, 83 years; 59.3% female), five subtypes were identified: (i) mild physical, (ii) mild cognitive, (iii) moderate physical, (iv) moderate multicomponent, and (v) severe multicomponent. The results of clustering were replicated in City B. Compared with the mild physical subtype, the severe multicomponent subtype showed the highest risk of death (adjusted hazard ratio [aHR] 2.56; 95% confidence interval [CI] 2.02–3.24), and nursing home admission (aHR 5.91; 95% CI 4.57–7.63). The moderate physical subtype showed a higher risk of hospitalization (aHR 1.32; 95% CI 1.16–1.49), and the moderate multicomponent subtype was more likely to experience care-need deterioration (adjusted odds ratio 1.67; 95% CI 1.26–2.22).

Conclusions and Implications

This study identified five subtypes of older adults who started LTC. These findings inform individualized care decisions and tailored planning of medical and LTC services.
Immune Cell Exhaustion and Apoptotic Markers in Major Depressive Disorder: Effects of in Vitro Cannabidiol Administration
Authors: Rachayon Muanpetch , Jirakran Ketsupar , Sodsai Pimpayao , Tunvirachaisakul Chavit , Sughondhabirom Atapol , Li Jing , Zhang Yingqian , Maes Michael
Published: December 2024

Background

Immune dysregulation is a component of Major Depressive Disorder (MDD). Cannabidiol (CBD) has immunomodulatory and putative antidepressant effects. The relationship between apoptotic and exhaustion immune markers and the clinical features of MDD and the effects of CBD on these markers are still unknown.

Objectives

To assess pro-apoptotic (CD95) and T cell exhaustion (TIM-3) markers on immune cells in patients with MDD, as well as the impact of in vitro CBD administration on these markers.

Methods

We recruited healthy controls and MDD patients and evaluated the immunophenotypes of T/B lymphocytes using flow cytometry in unstimulated and anti-CD3/CD28 stimulated conditions. We evaluated the immune profiles of M1 macrophages, T helper (Th)17 cells, immune-inflammatory response system (IRS), T cell proliferation, and immune-related neurotoxicity (IRN). We investigated the in vitro effects of CBD on immune cell subsets at concentrations of 0.1 µg/mL, 1 µg/mL, and 10.0 µg/mL.

Results

The stimulated CD3+CD95+ cell percentages were substantially correlated with the number of depressive episodes, recurrence of illness, and suicidal behaviors. The stimulated CD8+TIM-3+ cell percentages were substantially and inversely associated with the M1, IRS, CIRS, T cell growth, and IRN immune profiles. TIM-3+ bearing CD3+, CD4+ and CD8+,cells were significantly suppressed by lower CBD concentrations (0.1 – 1 µg/mL). TIM-3+ and all CD95+ bearing cells, with the exception of CD3+CD95+, were suppressed by the higher CBD concentrations.

Discussion

Aberrations in immune checkpoint molecular processes impact the features of MDD. CBD significantly impacts apoptotic and exhaustion processes thereby possibly interfering with immune homeostasis.
Sex hormone-binding globulin, testosterone and type 2 diabetes risk in middle-aged African women: exploring the impact of HIV and menopause
Authors: Goedecke Julia H. , Kufe Clement Nyuyki , Masemola Maphoko , Lichaba Mamosilo , Seipone Ikanyeng D. , Mendham Amy E , Gibson Hylton , Hawley James , Selva David M. , Magodoro Itai , Kengne Andre Pascal , Chikowore Tinashe , Crowther Nigel J. , Norris Shane A , Karpe Fredrik , Olsson Tommy , Storbeck Karl-Heinz , Micklesfield Lisa K.
Published: December 2024

Objectives

Sex hormone-binding globulin (SHBG) and testosterone are differentially associated with type 2 diabetes (T2D) risk. We investigated whether these associations differ by HIV and menopausal status in Black South African women living with (WLWH) and without HIV (WLWOH).

Design

Cross-sectional observational.

Methods

Eighty one premenopausal (57 WLWOH, 24 WLWH) and 280 postmenopausal (236 WLWOH, 44 WLWH) women from the Middle-Aged Soweto Cohort (MASC) completed the following measures: circulating SHBG and sex hormones, body composition (dual energy x-ray absorptiometry), oral glucose tolerance test to estimate insulin sensitivity (Matsuda index), secretion (insulinogenic index, IGI) and clearance, and beta-cell function (disposition index, DI). Dysglycaemia was defined as either impaired fasting or postprandial glucose or T2D.

Results

SHBG was higher and total and free testosterone were lower in postmenopausal WLWH than WLWOH (all p<0.023). Irrespective of HIV serostatus, SHBG was positively associated with Matsuda index, insulin clearance and DI and inversely with HOMA-IR (all p<0.011). The association between SHBG and Matsuda index was stronger in premenopausal than postmenopausal women (p=0.043 for interaction). Free testosterone (and not total testosterone) was only negatively associated with basal insulin clearance (p=0.021), and positively associated with HOMA-IR in premenopausal and not post-menopausal women (p=0.015 for interaction).

Conclusions

We show for the first time that midlife African WLWH have higher SHBG and lower total and free testosterone than WLWOH, which corresponded to their higher beta-cell function, suggesting a putative protective effect of SHBG on T2D risk in WLWH.

Significance statement

This study in midlife Black African women suggest that higher sex hormone binding protein (SHBG) and lower free testosterone in women living with HIV (WLWH) may be associated with reduced risk of type 2 diabetes (T2D) compared to women living without HIV. Further, this study provides a putative mechanism underlying the lower prevalence of T2D in WLWH and obesity compared to women living with obesity but without HIV. However, longitudinal studies are required to understand the clinical implications of these findings.
No one-size-fits-all approach: Retrospective analysis of efficacy and safety of serum concentrations of continuously administered vancomycin in critically ill adults reveals different target serum concentrations depending on disease severity
Authors: Viertel Katrin , van Meegen Carmen , Herbrandt Swetlana , Annecke Thorsten , Mattner Frauke
Published: December 2024

Background

Vancomycin is frequently monitored, but target levels for continuous infusion of vancomycin (CIV) are based on expert opinion. Rarely have vancomycin concentrations been correlated with therapeutic efficacy or safety of CIV.

Objectives

Associations between vancomycin steady-state serum concentrations and treatment failure or toxicity with CIV were examined.

Methods

A retrospective, single-centre cohort study was conducted of consecutive critically ill surgical patients receiving CIV between 2010-2022. After detecting associations between vancomycin levels, renal function and health status, four subgroups were defined based on estimated glomerular filtration rate (</≥90mL/min/1.73m²) and Simplified Acute Physiology Score (SAPS) II (≤/>36). Failure and toxicity of vancomycin serum concentrations were assessed using primary (mortality, acute kidney injury (AKI)) and secondary (clinical and microbiological failure) endpoints. Predictors of outcome parameters were identified using logistic and Cox regression. Concentrations were compared by bivariate comparisons, post-hoc tests following analysis of variance for the regression models and desirability of outcome ranking. Concentration cut-offs were determined by receiver-operating characteristic and classification and regression tree analyses.

Results

922 patients were included. Higher vancomycin concentrations (first 72h average; specifically >25mg/L) were associated with higher mortality, AKI and clinical failure, but less microbiological failure. For SAPS>36, concentrations <20mg/L (i.e. 15-20mg/L or <17mg/L) correlated with the best treatment outcome, for SAPS≤36 concentrations >19mg/L (i.e. 20-25mg/L or 19-28mg/L).

Conclusion

Retrospective analyses of vancomycin serum concentrations during CIV suggest that ICU patients’ disease severity should be considered when selecting a target concentration. The target concentration might be sought inversely related to SAPS, which should be confirmed in future prospective controlled trials.
Early effectiveness of the BNT162b2 KP.2 vaccine against COVID-19 in the US Veterans Affairs Healthcare System
Authors: Appaneal Haley J. , Lopes Vrishali V. , Puzniak Laura , Zasowski Evan J. , Jodar Luis , McLaughlin John M. , Caffrey Aisling R.
Published: December 2024

We conducted a test-negative case-control study within the US Veterans Affairs Healthcare System to estimate early vaccine effectiveness (VE) of the BNT162b2 KP.2 vaccine (Pfizer 2024-2025 formulation) against COVID-19 outcomes. Among 44,598 acute respiratory infections between September 5 and November 30, 2024, VE was 68% (42-82%), 57% (46-65%), and 56% (36-69%) against COVID-19-associated hospitalizations, emergency department and urgent care visits, and outpatient visits, respectively. Uptake of updated COVID-19 vaccines remains low.
Clonal expansion from standing genetic variation underpins the evolution of an emerging plant pathogen in Australia
Authors: Sparks Adam H. , Adorada Dante L. , Colombi Elena , Kelly Lisa A. , Young Anthony , Knight Noel L. , Vaghefi Niloofar
Published: December 2024

Pathogens can evolve rapidly, leading to the emergence of novel strains that can overcome commercially deployed host plant resistance. Understanding the genetic and phenotypic diversity and population dynamics of plant pathogens is crucial to inform breeding programs targeting resistance. Tan spot, otherwise known as bacterial wilt, caused byCurtobacterium flaccumfacienspv.flaccumfaciens, is a destructive disease of mungbean in Australia. Since the 1990s, several mungbean cultivars with partial resistance to tan spot have been released; however, cultivars initially rated as moderately resistant were later rated as moderately susceptible to tan spot. This study investigated the genetic and phenotypic diversity and temporal evolutionary dynamics ofC. flaccumfacienspv.flaccumfaciensin Australian mungbean fields. Whole-genome sequencing of 119 isolates collected from mungbean and other legumes (1986–2019) enabled analyses of pathogen evolution in Australia and in a global context. Results revealed that clonal expansion from standing genetic variation, rather than introduction of novel genotypes, has driven the evolution of this pathogen in Australia since the 1980s. Glasshouse trials confirmed the role of a plasmid in pathogenicity ofC. flaccumfacienspv.flaccumfaciensbut found no significant differences in aggressiveness between clonal lineages. This study underscores the importance of understanding pathogen diversity and aggressiveness to guide breeding programs for effective and durable disease resistance and highlights the need for further studies on the competitive fitness of isolates and characterisation of private alleles linked to dominant clonal lineages.

Significance

Tan spot is an increasingly significant pathogen affecting beans and mungbean worldwide, with a broad host range and quarantine importance in many countries underscoring the need for effective breeding strategies to manage the disease. Our research provides insights into genetic and phenotypic diversity of this important plant pathogen and temporal changes in its population structure in Australia, which are crucial for developing informed breeding strategies and managing the spread and impact of the disease. This work also underscores the critical need for robust, validated screening protocols and selection of aggressive, locally representative isolates for resistance breeding to ensure accurate assessment of resistance in crops for effective and durable resistance.
Modelling the potential use of pre-exposure prophylaxis to reduce nosocomial SARS-CoV-2 transmission
Authors: Stewart Lauren , Evans Stephanie , Brevini Teresa , Sampaziotis Fotios , Illingworth Christopher J. R.
Published: December 2024

The nosocomial transmission of respiratory pathogens is an ongoing healthcare challenge, with consequences for the health of vulnerable individuals. Outbreaks in hospitals can require the closure of bays or entire wards, reducing hospital capacity and having a financial impact upon healthcare providers. Here we evaluate a novel strategy of pre-exposure prophylaxis as a means to reduce the nosocomial transmission of SARS-CoV-2. We model the effect of ursodeoxycholic acid (UDCA) upon levels of ACE2 expression, SARS-CoV-2 viral entry, and ultimately the probability of an infection. We then implement this model within simulations describing the spread of SARS-CoV-2 infections within a hospital context, simulating an intervention in which UDCA is given to patients on a ward for 10 days following the detection of a case of SARS-CoV-2 on that ward. Under default model parameters we infer a potential 16.5% reduction (95% C. I. 14% - 20%) in the nosocomial transmission of SARS-CoV-2 to patients, with increased importation of cases into the hospital increasing the effectiveness of the intervention. Our study provides preliminary evidence of the value of pre-exposure prophylaxis with UDCA as a strategy to reduce nosocomial SARS-CoV-2 transmission.
Testing the Safety of the Nature Based Microbial Exposure with Atopic Dermatitis Patients – A Randomized, Placebo Controlled, Double-Blinded Pilot Trial
Authors: Kalmari Johanna , Mäkelä Iida , Kummola Laura , Roslund Marja , Huhtala Heini , Puhakka Riikka , Autio Pekka , Hyöty Heikki , Hytönen Vesa P , Sinkkonen Aki , Laitinen Olli H
Published: December 2024

Biodiversity hypothesis posits that it is beneficial for human health to be in contact to microbial biodiversity, and loss of this contact leads to immune-mediated diseases like atopy. Based on this hypothesis, we wanted to study if a lotion containing highly diverse natural microbes is a safe and feasible way to administer nature exposure to humans, and to study the effects of the exposure on the skin. We recruited two groups: 15 people with healthy skin and 12 people with atopic dermatitis. The healthy people were divided to the three groups that used twice daily a lotion containing: 1) 10 % of live microbial extract; 2) 10 % inactivated microbial extract; 3) placebo. The people with atopic dermatitis used a lotion containing 1 % of inactivated microbial extract in one side of their body and a placebo lotion in another side. The daily use of the lotion containing diverse microbial extract was well tolerated by both healthy and atopic people. Microbial extract in lotion did not change the relative abundance ofStaphylococcuson healthy skin in 14 day-trial and did not change atopic eczema severity, transepidermal water loss or erythema on atopic skin compared to placebo during 28-day trial. Atopic dermatitis patients can benefit from the overall effect of moisturizing lotion and the microbial extract, which together down-regulated pro-inflammatory IL-1β, IL-22, IL-33 cytokines, and antimicrobial peptide hBD-2 on atopic lesions indicating enhanced tolerance and mitigation of eczema. Nature exposure by microbial extract in lotion could complement current atopic dermatitis treatments.
A Novel Playbook for Pragmatic Trial Operations to Monitor and Evaluate Ambient Artificial Intelligence in Clinical Practice
Authors: Afshar Majid , Resnik Felice , Ryan Baumann Mary , Hintzke Josie , Sullivan Anne Gravel , Shah Tina , Stordalen Anthony , Oberst Michael , Dambach Jason , Mrotek Leigh Ann , Quinn Mariah , Abramson Kirsten , Kleinschmidt Peter , Brazelton Tom , Twedt Heidi , Kunstman David , Long John , Patterson Brian , Liao Frank , Rasmussen Stacy , Burnside Elizabeth , Goswami Cherodeep , Gordon Joel
Published: December 2024

Background

Ambient artificial intelligence offers promise for improving documentation efficiency and reducing provider burden through clinical note generation. However, challenges persist in workflow integration, compliance, and widespread adoption. This study leveraged a Learning Health System (LHS) framework to align research and operations using a hybrid effectiveness-implementation protocol, embedded as pragmatic trial operations within the electronic health record (EHR).

Methods

An alpha phase was conducted to pilot technical integration, refine workflows, and determine sample size in planning for a beta phase designed as a pragmatic randomized controlled trial with the Stanford Professional Fulfillment Index (PFI) as primary outcome. During alpha, bi-directional governance was established between IS operations and LHS team with multidisciplinary workgroups for analytics, technical, documentation, and user experience. Ambient AI was embedded into the EHR using Fast Healthcare Interoperability Resources (FHIR), with real-time data dashboards tracking utilization and documentation accuracy for operations and research. Performance metrics were monitored serially using a difference-in-differences (DiD) analysis to detect drift caused by software workflow changes.

Results

The alpha phase, designed as Type 1 Hybrid, informed a 24-week beta phase stepped-wedge trial with 90% power to detect changes in PFI. Across the alpha phase, the weighted median of average provider Ambient AI utilization was 65.4% following Plan-Do-Study-Act cycles addressing organizational feasibility and task-dependent adoption. During initial implementation, a workflow issue caused discrepancies between ICD-10 diagnosis entries and note content, reducing accuracy from 79% to 35% (p < 0.01). After implementing a new note template and provider training, accuracy returned to pre-intervention levels. DiD did not detect significant drifts in work outside of work or time in notes two weeks before and after the new note template. Beta phase enrollment achieved its targeted 66 providers across eight specialties, initiating on schedule.

Conclusions and Relevance

We provide a novel playbook for integrating Generative AI platforms in healthcare, combining pragmatic trial operations, human-centered design, and real-time monitoring to advance evidence-based implementation.

ClinicalTrials.gov ID

NCT06517082
Accessing AI mammography reports impacts patient interest in pursuing a medical malpractice claim: The unintended consequences of including AI in patient portals
Authors: Song Elizabeth C. , Bernstein Michael H. , Lay Parker S. , Druart Leo , Dibble Elizabeth H. , Lourenco Ana P. , Baird Grayson L.
Published: December 2024

Background

Artificial intelligence (AI) tools are increasingly used in breast imaging and radiology more broadly. Patients express varying levels of trust and acceptance toward the incorporation of AI tools, although no research has examined how it can best be communicated in the patient portal setting.

Methods

English-speaking US women with 1+ prior mammogram were recruited via Prolific and randomized to one of thirteen conditions. All participants were shown a vignette asking them to imagine receiving a BI-RADS 1 (Negative) radiologist report from their patient portal. Participants in twelve conditions also received an AI report with one of four AI abnormality scores (not flagged: 0, 29; flagged: 31, 50) and 0-2 accompanying features (nothing; a only; a & b): (a) an abnormality cutoff threshold; (b) the AI tool’s False Discovery Rate (FDR) or False Omission Rate (FOR). As the primary outcome, participants indicated whether they would consider a lawsuit if a one-year follow-up found evidence of Stage 3 breast cancer. Secondary outcomes included hypothetical decisions regarding follow-up (e.g., second opinions), concern for breast cancer, and desire for additional imaging.

Results

Participants (n=1,623) were more likely to consider a lawsuit when AI was (versus was not) provided, p=0.001. However, for most AI abnormality scores, providing the abnormality cutoff threshold and FDR/FOR reduced lawsuit consideration relative to the AI abnormality score alone. Concern for breast cancer, desire for additional imaging, and follow-up requests (same radiologist, different radiologist, and ordering physician) increased as the AI abnormality score increased, though this was also often mitigated by providing the FDR (and sometimes FOR).

Conclusion

Disclosing AI feedback used for medical decision-making will impact patients’ perceptions and behaviors pertaining to malpractice and follow-up. Best practices are needed to engage and inform patients about the application of AI tools in their care while minimizing its unintended negative consequences.
CD8 and vimentin were associated with overall survival in patients with ovarian cancer treated with intraperitoneal chemotherapy
Authors: Kim Hyojin , Lee Ji Eun , Lee Yong Jae , Kim Kidong
Published: December 2024

Objective

To identify immunohistochemistry markers affecting the survival in patients with ovarian cancer receiving intraperitoneal (IP) chemotherapy.

Methods

A retrospective review of medical records identified 24 patients with newly diagnosed stage III or IV high-grade serous ovarian carcinoma who underwent more than three cycles of IP chemotherapy at a tertiary hospital in Republic of Korea between 1990 and 2013. Immunohistochemical staining of tumor tissue for CD8, FOXP3, PDL1, E-cad and vimentin was performed. The level of expression was measured using established protocols of each marker and was dichotomized (high vs. low) using median value. The association of level of expression of each marker with progression-free survival (PFS) or overall survival (OS) were examined.

Results

The mean age was 44 years (range 27 to 59) and 23 patients were stage III. The median PFS was 15.3 months (range 0.4 to 148.3) and that of OS was 63.3 months (range 0.4 to 163.0). None of 5 markers were associated with PFS. However, CD8 (p=0.2) and vimentin (p=0.1) were marginally associated with OS. Patients with high CD8 or vimentin expression demonstrated a numerically longer PFS compared to those with low expression of both markers (median 19.7 months vs. 13.0 months,p= 0.073). Furthermore, patients with high CD8 or vimentin expression showed significantly improved OS compared to those with low expression of both markers (median 94.5 months vs. 25.4 months,p= 0.008).

Conclusion

CD8 and vimentin expression were correlated with OS in patients with ovarian carcinoma treated with IP chemotherapy.
GDBIG: the first birth cohort genomic database and platform facilitating intergenerational genetic research
Authors: Huang Shujia , Wang Chengrui , Huang Mingxi , Lu Jinhua , He Jian-Rong , Lin Shanshan , Liu Siyang , Xia Huimin , Qiu Xiu
Published: December 2024

High-quality genome databases derived from large-scale family-based birth cohorts are essential resources for investigating genetic determinants affecting early-life traits and the impact of early-life environments on the health of both parents and offspring. Here, we have established the genome database of Born in Guangzhou Cohort Study (BIGCS), name as GDBIG, which represents the first birth-cohort-based genomic database in China and is designed to facilitate generational genetic research, based on the Phase I results of BIGCS, that contains the low-coverage (∼6.63x) whole-genome sequencing (WGS) data and numerous pregnancy phenotypes of 4,053 Chinese participants. The participants were from 30 out of 34 administrative divisions of China, covering Han and 12 minority ethnic groups. Currently, GDBIG provides a comprehensive range of services, including allele frequency inquiries for 56.23 million variants across two generations, a genotype imputation server featuring a high-quality family-based reference panel, and a GWAS meta-analysis interface for various maternal and infant phenotypes. The GDBIG database addresses the dearth of Asian birth-cohort-based genomic resources and provides a valuable platform for conducting genetic analysis online or through application programming interfaces athttp://gdbig.bigcs.com.cn/.
Latrophilin-3conditional knockout in tyrosine hydroxylase neurons (Lphn3-Th- Cre) Compared withLphn3Global KO rats: Role ofLphn3in Tyrosine Hydroxylase Neurons on the Cognitive and Behavioral Effects of this ADHD Susceptibility Gene
Authors: Regan Samantha L. , Sugimoto Chiho , Lingo Aliyah N. , Tepe Erin A. , Williams Michael T. , Vorhees Charles V.
Published: December 2024

Latrophilin-3 (LPHN3) is a brain specific adhesion G-protein coupled receptor associated with elevated risk of attention deficit hyperactivity disorder (ADHD). We developed a globalLphn3knock-out (gKO) rat using CRISPR/Cas9 to delete exon-3. Here we report the development of a floxedLphn3rat crossed with tyrosine hydroxylase (Th-Cre) rats to create a conditionalLphn3KO rat specific for catecholaminergic- positive cells. The gKO rats are hyperactive and have egocentric and allocentric navigation deficits but showed sparing of conditioned contextual and novel object recognition memory. Here we compared gKO and cKO rats controlling for litter effects. Both gKO and cKO rats were hyperactive and were impaired in egocentric navigation in the Cincinnati water maze (CWM) with deficits greater in gKO rats. The gKO rats were impaired in allocentric navigation in the Morris water maze (MWM) whereas cKO rats were only slightly affected compared with WT, cre, and floxed rats. Striatal tyrosine hydroxylase and dopamine D1 receptors were not significantly different in either model, nor were NMDA-NR1 or NMDA-NR2 in the hippocampus. We previously showed, however, that dopamine is released more rapidly in the striatum of gKO rats by fast- scan cyclic voltammetry. The cKO model shows an important role of catecholamines in the phenotype of LPHN3 disruption and add evidence that this synaptic protein plays a role in neuroplasticity that are consistent with ADHD.
Exploring natural allies: Survey and identification of larval parasitoids for sustainable grape berry moth management in vineyards
Authors: Gomez-Llano Jesus H. , Khanal Neetu , Acevedo Flor E.
Published: December 2024

The American grape berry moth (GBM),Paralobesia viteanaClemens (Lepidoptera: Tortricidae) is an economically important pest of grapes. The larvae of this insect burrow inside the fruit upon hatching, consuming, and contaminating grapes and clusters. Current GBM management relies on pesticide applications, which do not offer complete protection due to the cryptic behavior of the larvae and asynchrony in egg-laying, highlighting the need to develop new management strategies. In this study, we identified GBM larval parasitoids in commercial vineyards and quantified their parasitism rates. Parasitoid samplings were conducted biweekly in six conventionally managed Concord vineyards in Erie County, Pennsylvania, during the 2023 and 2024 growing seasons. GBM-infested samples were monitored daily to track the emergence of both parasitoids and GBM, enabling the calculation of parasitism rates. We identified eight parasitoid species:Enytus obliteratus,Campoplex tortricidae,Scambussp,Glypta depressacf,Glypta ohioensiscf, andGlypta ignotacf. (Hymenoptera: Ichneumonidae);Bracon variabilis(Hymenoptera: Braconidae), andGoniozus fratellus(Hymenoptera: Bethylidae) praying on GBM larvae. From these,B. variabilis,E. obliteratus, andG. fratelluswere the most abundant. We also designed a graphic taxonomic key to facilitate the identification of these species. The parasitoid abundance differed over the growing season but was greatest in early August, reaching parasitism rates of up to 39% and 52.1% in 2023 and 2024, respectively. Our results demonstrate that GBM has several larval parasitoids that help reduce its populations in commercial vineyards. This project represented a first step toward our understanding of the GBM native natural enemies present in the Lake Erie Region and their potential use in management programs.
Phenolic compounds inMedicago truncatularoots are under the influence ofAgrobacterium fabrumthrough its species specific-genes regions
Authors: Padilla Rosa , Vial Ludovic , Dechèvre Florence , Thi Huyen Thu Nguyen , Gaillard Vincent , Meiffren Guillaume , Comte Gilles , Nesme Xavier , Lavire Céline , Kerzaon Isabelle
Published: December 2024

The impact of plant microbiota on the health and physiology of their host is increasingly studied and recognized. However, in the rhizosphere, the functions of most bacteria and the genetic determinants involved in the molecular dialogue between plant and bacteria are poorly understood. Agrobacteria are ubiquitous soil borne and rhizospheric bacteria able to establish commensal or even beneficial interactions with plant roots. The genomic speciesAgrobacterium fabrumharbor seven specific-regions (SpG8-1 to SpG8-7), whose annotation seems to indicate a close connection with the plant during plant-bacteria interactions. To evaluate the involvement ofA. fabrum-specific regions in the plant-bacteria interaction, deletion mutant strains of eachA. fabrum-specific region were inoculated onMedicago truncatularoots. Root metabolite profiles were compared by UHPLC-UV/DAD-ESI-MS QTOF analyses, and the highlighted discriminating metabolites were annotated by tandem mass spectrometry. Metabolomic analyses have shown thatA. fabruminoculation modulates the content of phenolic compounds inM. truncatularoots, in particular flavonoids. These root metabolite modulations observed with the wild-type strain often appear to be linked to at least one of theA. fabrum-specific genes, as almost allA. fabrum-specific regions showed an influence on one or more of these specialized root metabolites. In addition, our results underlined a putative cross-talk or coordinated effect of theA. fabrum-specific regions during the interaction ofA. fabrumwithM. truncatula, as all mutants except one induced similar modifications on flavonoids. These results contribute to a better understanding of the ecological niche construction ofA. fabrumhighlighting the importance of its specific genes in the establishment of this fine-tuned interaction.