bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anomalous left coronary artery from the pulmonary artery in a symptomatic adult: a case report
Authors: KC Sharada , Karki Parag , Khatiwada Abhikanta , Pokhrel Saroj 
Published: August 2024

Introduction:
Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly. While only a few of those born with this anomaly survive into adulthood, it becomes an extremely rare diagnosis in adults.

Case presentation:
Here, the authors present a case of ALCAPA in a symptomatic adult female with angina and palpitations that was repeatedly missed on transthoracic echocardiogram.

Clinical discussion:
The adult type of ALCAPA is often missed due to non-specific changes in electrocardiogram, leading to reluctance for angiography. Therefore, identifying abnormal coronaries in echocardiogram is crucial.

Conclusion:
It is essential to consider anomalous coronary arteries as a differential diagnosis in patients with chest pain, despite their rarity. This case report highlights the role of various cardiac imaging modalities in improving the diagnostic yield of ALCAPA.
Using a Patient Portal to Screen Patients for Symptoms After Starting New Medications
Authors: Shah Sonam , Salazar Alejandra , Bennett Samuel , Fathima Aneesha , Kandikatla Renuka , Eguale Tewodros , Mirica Maria , Garabedian Pamela , Volk Lynn A. , Wright Adam , Schiff Gordon D. 
Published: August 2024

Objective
Conduct systematic proactive pharmacovigilance screening for symptoms patients experienced after starting new medications using an electronic patient portal. We aimed to design and test the feasibility of the system, measure patient response rates, provide any needed support for patients experiencing potentially drug-related problems, and describe types of symptoms and problems patients report.

Methods
We created an automated daily report of all new prescriptions, excluding likely non-new and various over-the-counter meds, and sent invitations via patient portal inviting patients to inquire if they had started the medication, and if “yes,” inquire if they had they experienced any new symptoms that could be potential adverse drug effects. Reported symptoms were classified by clinical pharmacists using SOC MeDra taxonomy, and patients were offered follow-up and support as desired and needed.

Results
Of 11,724 included prescriptions for 9360 unique patients, 2758 (29.4%) patients responded. Of 2616 unique medication starts, patients reported at least 1 new symptom that represented a potential adverse drug reaction (ADR) in 678/2616 (25.9%). Nearly one-third of those experiencing new symptoms (30.3%) reported 2 or more new symptoms after initiating the drug. GI disorders accounted for 30% of the total reported ADRs.

Conclusions
Systematic portal-based surveillance for potential adverse drug reactions was feasible, had higher response rates than other methods (such as automated interactive phone calling), and uncovered rates of potential ADRs (roughly 1 in 4 patients) consistent with other methods/studies.
Survival and Prognostic Factors After Adrenalectomy for Secondary Malignancy
Authors: Rémond Agathe , Marciniak Camille , Lenne Xavier , Chouraki Vincent , Gobert Mathilde , Baud Gregory , Maillard Laure , Bouriez Damien , Liekens Ellen , Donatini Gianluca , Nominé-Criqui Claire , Ravenet Ambroise , Santucci Nicolas , Kuczma Paulina , Bouviez Nicolas , Tresallet Christophe , Mirallié Eric , Deguelte Sophie , Brunaud Laurent , Guerin Carole , Gronnier Caroline , Lifante Jean-Christophe , Bruandet Amélie , Theis Didier , Cortot Alexis , Scherpereel Arnaud , Hamroun Aghiles , Pattou François , Caiazzo Robert 
Published: August 2024

Objective:
To provide a nationwide description of postoperative outcomes and analysis of prognostic factors following adrenalectomy for metastases.

Background:
Adrenal glands are a common site of metastases in many malignancies. Diagnosis of adrenal metastases is on the rise, leading to an increasing number of patient candidates for surgery without consensual management.

Methods:
We conducted a population-based study between January 2012 and December 2022 using the French National Health Data System (SNDS) and the Eurocrine registry (NCT03410394). The first database exhaustively covers all procedures carried out in France, while the second provides more clinical information on procedures and tumor characteristics, based on the experience of 11 specialized centers.

Results:
From the SNDS, we extracted 2515 patients who underwent adrenalectomy for secondary malignancy and 307 from the Eurocrine database. The most common primary malignancies were lung cancer (n=1203, 47.8%) and renal cancer (n=555, 22.1%). One-year survival was 84.3% (n=2120). Thirty-day mortality and morbidity rates were, respectively, 1.3% (n=32) and 29.9% (n=753, including planned intensive care unit - stays). Radiotherapy within the year before adrenalectomy was significantly associated with higher 30-day major complication rates (P=0.039). In the Eurocrine database, the proportion of laparoscopic procedures reached 85.3% without impairing resection completeness (R0: 92.9%). Factors associated with poor overall survival were the presence of extra-adrenal metastases (hazard ratio =0.64; P=0.031) and incomplete resection (≥R1; hazard ratio=0.41; P=0.015).

Conclusions:
The number of patients who can receive local treatment for adrenal metastases is rising, and adrenalectomy is more often minimally invasive and has a low morbidity rate. Subsequent research should evaluate which patients would benefit from adrenal surgery.
Urinary AD7c-NTP is Associated With Cognitive Recovery After Ischemic Stroke
Authors: Wang Yuqin , Tao Huimin , Cao Maohong , Cai Kefu 
Published: August 2024

Urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) is regarded as a biomarker for β-amyloid protein deposition in Alzheimer disease (AD). The value of AD7c-NTP in predicting post-stroke cognitive recovery was worth exploring. In total, 224 patients with first-ever stroke were enrolled in this retrospective study. Cognitive assessment was evaluated by Mini-Mental State Examination (MMSE), and cognitive improvement was defined as MMSE scores ≥27 or 4-score elevation at 3-month follow-up after stroke. The AD7c-NTP level was 0.68±0.40 ng/mL in the 135 patients with cognitive improvement, while the AD7c-NTP level was 1.49±0.99 ng/mL in the 89 patients without improvement (P<0.001). Those displaying better cognitive recovery also had younger ages, higher MMSE scores, and lower NIHSS scores on admission. In multivariable logistic regression analysis, AD7c-NTP concentration (OR=9.14, 95% CI: 4.52-18.49, P<0.001), age (OR=1.04, 95% CI: 1.01-1.08, P=0.012), and NIHSS score on admission (OR=1.17, 95% CI: 1.07-1.28, P<0.001) remained the independent risk factors affecting cognitive recovery. The area under the receiver operating characteristics curve for AD7c-NTP in predicting unfavorable cognitive function was 0.80 (sensitivity: 0.73 and specificity: 0.84). Urinary AD7c-NTP is a valuable biomarker associated with post-stroke cognitive recovery. It might be adopted to discriminate coexisting AD pathology from vascular cognitive impairment.
Endothelial Immunosuppression in Atherosclerosis : Translational Control by Elavl1/HuR
Authors: Nicholas Sarah-Anne E. , Helming Stephen R. , Ménoret Antoine , Pathoulas Christopher , Xu Maria M. , Hensel Jessica , Kimble Amy L. , Heineman Brent , Jellison Evan R. , Reese Bo , Zhou Beiyan , Rodriguez-Oquendo Annabelle , Vella Anthony T. , Murphy Patrick A. 
Published: August 2024

AbstractAtherosclerotic plaques are defined by the accumulation of lipids and immune cells beneath the endothelium of the arterial intima. CD8 T cells are among the most abundant immune cell types in plaque, and conditions linked to their activation correlate with increased levels of cardiovascular disease. As lethal effectors of the immune response, CD8 T cell activation is suppressed at multiple levels. These checkpoints are critical in dampening autoimmune responses, and limiting damage in cardiovascular disease.Endothelial cells are well known for their role in recruiting CD8 T and other hematopoietic cells to low and disturbed flow (LDF) arterial regions that develop plaque, but whether they locally influence CD8 effector functions is unclear. Here, we show that endothelial cells can actively suppress CD8 T cell responses in settings of chronic plaque inflammation, but that this behavior is governed by expression of the RNA-binding protein Embryonic Lethal, Abnormal Vision-Like 1 (Elavl1). In response to immune cell recruitment in plaque, the endothelium dynamically shifts splicing of pre-mRNA and their translation to enhance expression of immune-regulatory proteins including C1q and CD27. This program is immuno-suppressive, and limited by Elavl1. We show this byCdh5(PAC)-CreERT2-mediated deletion of Elavl1 (ECKO), and analysis of changes in translation by Translating Ribosome Affinity Purification (TRAP). In ECKO mice, the translational shift in chronic inflammation is enhanced, leading to increased ribosomal association of C1q components and other critical regulators of immune response and resulting in a ∼70% reduction in plaque CD8 T cells. CITE-seq analysis of the remaining plaque T cells shows that they exhibit lower levels of markers associated with T cell receptor (TCR) signaling, survival, and activation. To understand whether the immunosuppressive mechanism occurred through failed CD8 recruitment or local modulation of T cell responses, we used a novelin vitroco-culture system to show that ECKO endothelial cells suppress CD8 T cell expansion—even in the presence of wild-type myeloid antigen-presenting cells, antigen-specific CD8 T cells, and antigen. Despite the induction of C1q mRNA by T cell co-culture in both wild-type and ECKO endothelial cells, we find C1q protein abundantly expressed only in co-culture with ECKO cells. Together, our data define a novel immune-suppressive transition in the endothelium, reminiscent of the transition of T cells to T-regs, and demonstrate the regulation of this process by Elavl1.
GPSA2: combining landmark-free and landmark-based methods in geometric morphometrics
Authors: Pomidor Benjamin J. , Dean Matt 
Published: August 2024

ABSTRACTGeometric Morphometrics (GM) revolutionized the way that biologists quantify shape variation among individuals, populations, and species. Traditional GM methods are based on homologous landmarks that can be reliably identified across all specimens in a sample. However, landmark-based studies are limited by the intensive labor required of anatomical experts, and regions of interest are often devoid of landmarks. These limitations inspired the development of many “landmark-free” approaches, but unreliable homology estimation and complicated underlying mathematical bases can make biological interpretation challenging. Here we present GPSA2, a novel method for analyzing surface meshes that combines landmark-based and landmark-free methodology within the familiar framework of Generalized Procrustes Analysis. In a major innovation, our method can incorporate user-defined landmarks into otherwise landmark-free analysis by transforming the landmarks into pointwise shape descriptors that are exploited during iterative homology estimation and superimposition (i.e. “alignment” of objects). GPSA2 also addresses a longstanding issue in morphometrics – the impact of variability in the distribution of sampled points over an object – by introducing a surface area-weighted shape distance metric and superimposition cost function. The improved homology approximation, together with the application of Taubin smoothing and an optional resistant-fit superimposition technique, ensure robust analysis even when a dataset exhibits regions of intense shape variation. We apply GPSA2 to two empirical datasets: 15 primate skulls and 369 mouse bacula. Our analyses show that inclusion of landmarks increases biological accuracy, and that GPSA2 produces summaries of shape variation that are easy to visualize and interpret.
Characterization of aberrant splicing in pediatric central nervous system tumors revealsCLK1as a candidate oncogenic dependency
Authors: Naqvi Ammar S. , Corbett Ryan J. , Seghal Priyanka , Conkrite Karina L. , Rathi Komal S. , Ennis Brian M. , Hayer Katharina E , Zhang Bo , Brown Miguel A. , Miller Daniel P. , Kraya Adam A. , Coleman Kaleem L. , Dybas Joseph M. , Geng Zhuangzhuang , Blackden Christopher , Arif Shehbeel , Chroni Antonia , Lahiri Aditya , Hollawell Madison L. , Storm Phillip B. , Haydar Dalia , Foster Jessica B. , Koptyra Mateusz , Madsen Peter J. , Diskin Sharon J. , Thomas-Tikhonenko Andrei , Resnick Adam C. , Rokita□ Jo Lynne 
Published: August 2024

SummaryPediatric brain cancer is the leading cause of disease-related mortality in children, and many aggressive tumors still lack effective treatment strategies. We characterized aberrant alternative splicing across pediatric brain tumors, identifying pediatric high-grade gliomas (HGGs) among the most heterogeneous. Annotating these events with UniProt, we identified 11,940 splice events in 5,368 genes leading to potential protein function changes. We discoveredCDC-like kinase 1(CLK1) is aberrantly spliced to favor exon 4 inclusion, resulting in a gain of two phosphorylation sites and subsequent activation. Inhibition ofCLK1with Cirtuvivint significantly decreased both cell viability and proliferation in the pediatric HGG KNS-42 cell line. Morpholino-mediated depletion ofCLK1exon 4 splicing reduced RNA expression, protein abundance, and cell viability with concurrent differential expression of 78 cancer genes and differential splicing at functional sites in 193 cancer genes. Our findings highlight a dependency of pediatric HGGs onCLK1and represent a promising therapeutic strategy.HighlightsSplice variation across pediatric CNS tumors from 1,415 patients is heterogeneousIn HGGs, 11,940 splice events in 5,368 genes contain functional sitesCLK1exon 4 inclusion is prevalent in HGGs, driving canonical expressionCLK1splicing impacts cancer genes, phenotypes, and is therapeutically targetable
Understanding Electrical Brain Stimulation via the Reciprocity Theorem
Authors: Ness Torbjørn V. , Koch Christof , Einevoll Gaute T. 
Published: August 2024

AbstractElectrical stimulation of nervous tissue is grounded in well-established biophysical principles, yet understanding its precise effect on neural activity remains challenging. This represents a major obstacle to both scientific and clinical applications of electrical brain stimulations.We here show that the reciprocity theorem of electromagnetism can be applied more broadly than previously acknowledged, providing a framework for elucidating the effects of electrical brain stimulation on neurons. Through this perspective, we account for the observed weak frequency-dependence of extracellular stimulation–induced membrane potential changes, and the 1/rfalloff for nearby and 1/r2falloff for distant neurons. We also show that transcranial electrical stimulation at established safety limits (<4 mA) induces somatic membrane potential changes less than 0.1 mV in pyramidal cells, exhibiting weak spatial but strong orientation dependency across human neocortex.
The scope and limits of fine-grained image and category information in the ventral visual pathway
Authors: Badwal Markus W. , Bergmann Johanna , Roth Johannes , Doeller Christian F. , Hebart Martin N. 
Published: August 2024

AbstractHumans can easily abstract incoming visual information into discrete semantic categories. Previous research employing functional MRI (fMRI) in humans has identified cortical organizing principles that allow not only for coarse-scale distinctions such as animate versus inanimate objects but also more fine-grained distinctions at the level of individual objects. This suggests that fMRI carries rather fine-grained information about individual objects. However, most previous work investigating fine-grained category representations either additionally included coarse-scale category comparisons of objects, which confounds fine-grained and coarse-scale distinctions, or only used a single exemplar of each object, which confounds visual and semantic information. To address these challenges, here we used multisession human fMRI (female and male) paired with a broad yet homogenous stimulus class of 48 terrestrial mammals, with 2 exemplars per mammal. Multivariate decoding and representational similarity analysis (RSA) revealed high image-specific reliability in low- and high-level visual regions, indicating stable representational patterns at the image level. In contrast, analyses across exemplars of the same animal yielded only small effects in the lateral occipital complex (LOC), indicating rather subtle category effects in this region. Variance partitioning with a deep neural network and shape model showed that across exemplar effects in EVC were largely explained by low-level visual appearance, while representations in LOC appeared to also contain higher category-specific information. These results suggest that representations typically measured with fMRI are dominated by image-specific visual or coarse-grained category information but indicate that commonly employed fMRI protocols may reveal subtle yet reliable distinctions between individual objects.Significance StatementWhile it has been suggested that functional MRI (fMRI) responses in ventral visual cortex carry fine-grained information about individual objects, much previous research has confounded fine-grained with coarse-scale category information or only used individual visual exemplars, which potentially confounds semantic and visual object information. Here we address these challenges in a multisession fMRI study where participants viewed a highly homogenous stimulus set of 48 land mammals with 2 exemplars per animal. Our results reveal a strong dominance of image-specific effects and additionally indicate subtle yet reliable category-specific effects in lateral occipital complex, underscoring the capacity of commonly employed fMRI protocols to uncover fine-grained visual information.
Bacterial strain sharing between humans, animals, and the environment among urban households
Authors: Kim Daehyun D. , Swarthout Jenna M. , Worby Colin J. , Chieng Benard , Mboya John , Earl Ashlee M. , Njenga Sammy M. , Pickering Amy J. 
Published: August 2024

AbstractIdentifying bacterial transmission pathways is crucial to inform strategies aimed at curbing the spread of pathogenic and antibiotic-resistant bacteria, especially in rapidly urbanizing low– and middle-income countries. In this study, we assessed bacterial strain-sharing and dissemination of antibiotic resistance across humans, domesticated poultry, canines, household soil, and drinking water in urban informal settlements in Nairobi, Kenya. We collected 321 samples from 50 households and performed Pooling Isolated Colonies-seq (PIC-seq) by sequencing pools of up to fiveEscherichia colicolonies per sample to capture strain diversity, strain-sharing patterns, and overlap of antibiotic-resistant genes (ARGs). Bacterial strains isolated from the household environment carried clinically relevant ARGs, reinforcing the role of the environment in antibiotic resistance dissemination. Strain-sharing rates and resistome similarities across sample types were strongly correlated within households, suggesting clonal spread of bacteria is a main driver of dissemination of ARGs in the domestic urban environment. Within households,E. colistrain-sharing was rare between humans and animals but more frequent between humans and drinking water.E. colicontamination in stored drinking water was also associated with higher strain-sharing between humans in the same household. Our study demonstrates that contaminated drinking water facilitates human to human strain sharing and water treatment can disrupt transmission.
Prenatal Dexamethasone Programs Autonomic Dysregulation in Female Rats
Authors: Madhavpeddi Lakshmi , Martinez Monique , Alvarez Jared , Sharma Arpan , Hu Chengcheng , Tobet Stuart A , Hale Taben M 
Published: August 2024

AbstractAutonomic dysfunction is associated with cardiovascular and neurological disease, including hypertension, heart failure, anxiety, and stress-related disorders. Prior studies demonstrated that late gestation exposure to dexamethasone (DEX) resulted in female-biased increases in stress-responsive mean arterial pressure (MAP) and heart rate (HR), suggesting a role for glucocorticoid-mediated programming of autonomic dysfunction. The present study investigated the influence of sympathetic (SYM) or parasympathetic (PS) blockade on cardiovascular function in male and female rat offspring of mothers injected with DEXin utero(gestation days [GD]18-21). At 11-12-weeks of age, MAP, HR, and heart rate variability (HRV) were evaluated at baseline and in response to SYM antagonists (α1-adrenoceptor + β1-adrenoceptor), a PS (muscarinic) antagonist, or saline (SAL). To assess stress-responsive function, rats were exposed to acute restraint. Tyrosine hydroxylase was measured in adrenals and left ventricle, and gene expression for the β1adrenergic receptor was measured in left ventricle. Maternal DEX injection reduced basal HRV in male and female offspring. SYM blockade attenuated increases in stress-responsive HR and MAP. PS blockade elevated stress-responsive HR and MAP to a greater extent in Vehicle females. SYM and PS blockade produced equivalent effects on HR and MAP responses in male offspring, regardless of maternal treatment. Based on these findings, we suggest that maternal DEX injection disrupted autonomic regulation of cardiovascular function in females, resulting in a shift toward greater SYM input and less input from PS. Future studies will investigate whether changes in autonomic function are mediated by changes in central autonomic circuitry.New and NoteworthyThese studies use pharmacological antagonists to characterize the nature of the autonomic dysregulation induced in female offspring exposed to the synthetic glucocorticoid, dexamethasone,in utero. The female offspring of dams injected with dexamethasone in late gestation show a reduction in vulnerability to parasympathetic blockade and an increase in responses to acute restraint stress even in the presence of sympathetic blockade. This suggests that late gestation dexamethasone disrupts the normal development of the autonomic function in females leading to a shift in the sympathovagal balance.
Optic flow density modulates corner-cutting independently of age in a virtual reality steering task
Authors: Giguere Arianna P. , Huxlin Krystel R. , Tadin Duje , Fajen Brett R. , Diaz Gabriel J. 
Published: August 2024

ABSTRACTThere is a critical need to understand how aging visual systems contribute to age-related increases in vehicle accidents. We investigated the potential contribution of age-related detriments in steering based on optic flow, a source of information known to play a role in navigation control. Seventeen younger adults (mean age: 21.1 years) and thirteen older adults (mean age: 57.3 years) performed a virtual reality steering task. The virtual environment depicted movement at 19 m/s along a winding road. Participants were tasked with maintaining a central lane position while experiencing 8 repetitions of each combination of optic flow density (low, medium, high), turn radius (35, 55, 75 meters), and turn direction (left, right), presented in random order. All participants cut corners, but did so less on turns with rotational flow from distant landmarks and without proximal optic flow. The magnitude of this flow-related effect was independent of age, although older adults cut corners more on all turns. An exploratory gaze analysis revealed no age-related differences in gaze behavior. The lack of age-related differences in steering or gaze behavior as a function of optic flow implies that processing of naturalistic optic flow stimuli when steering may be preserved with age.