bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulation of hepatic one‐carbon metabolism in classical homocystinuria: Implications of redox‐sensitive DHFR repression and tetrahydrofolate depletion for pathogenesis and treatment
Authors: Maclean Kenneth N. , Jiang Hua , Neill Philip D. , Chanin Ryan R. , Hurt K. Joseph , Orlicky David J. , Bottiglieri Teodoro , Roede James R. , Stabler Sally P. 
Published: July 2024

AbstractCystathionine beta‐synthase‐deficient homocystinuria (HCU) is a life‐threatening disorder of sulfur metabolism. HCU can be treated by using betaine to lower tissue and plasma levels of homocysteine (Hcy). Here, we show that mice with severely elevated Hcy and potentially deficient in the folate species tetrahydrofolate (THF) exhibit a very limited response to betaine indicating that THF plays a critical role in treatment efficacy. Analysis of a mouse model of HCU revealed a 10‐fold increase in hepatic levels of 5‐methyl ‐THF and a 30‐fold accumulation of formiminoglutamic acid, consistent with a paucity of THF. Neither of these metabolite accumulations were reversed or ameliorated by betaine treatment. Hepatic expression of the THF‐generating enzyme dihydrofolate reductase (DHFR) was significantly repressed in HCU mice and expression was not increased by betaine treatment but appears to be sensitive to cellular redox status. Expression of the DHFR reaction partner thymidylate synthase was also repressed and metabolomic analysis detected widespread alteration of hepatic histidine and glutamine metabolism. Many individuals with HCU exhibit endothelial dysfunction. DHFR plays a key role in nitric oxide (NO) generation due to its role in regenerating oxidized tetrahydrobiopterin, and we observed a significant decrease in plasma NOx (NO2 + NO3) levels in HCU mice. Additional impairment of NO generation may also come from the HCU‐mediated induction of the 20‐hydroxyeicosatetraenoic acid generating cytochrome CYP4A. Collectively, our data shows that HCU induces dysfunctional one‐carbon metabolism with the potential to both impair betaine treatment and contribute to multiple aspects of pathogenesis in this disease.
Portal vein thrombosis associated with acute cholecystitis
Authors: Lehner Leanna , Sarap Michael 
Published: July 2024

ABSTRACT
Portal venous thrombosis (PVT) is an uncommon clinical problem and is rare following cholecystectomy. This article describes a patient who developed PVT after an initially uneventful laparoscopic cholecystectomy. The patient was successfully treated with IV antibiotics and anticoagulation.
Clinical oncology pharmacy has become a reality: results of a member survey of the European Society of Oncology Pharmacy Global
Authors: Spasovska Olivera , Bardin Christophe , Kuzmanović Maja , Cortés Constanza , Assefa Tadesse Tamrat , Crul Mirjam 
Published: July 2024

Abstract

Introduction:
The European Society of Oncology Pharmacy (ESOP) Global has almost 4000 members across 70 countries. Over the past few decades, the focus of oncology pharmacists has shifted, from a mostly product-based role to include a patient-centric care model, often termed clinical pharmacy. To map the advancement of the integration of clinical pharmacy into daily oncology pharmacy practice, a survey was conducted among the members of the ESOP Global in 2023.

Methods:
A survey comprising 28 questions was distributed across the full ESOP Global membership. Questions were grouped to obtain demographic results (first section), the practice of clinical pharmacy (second section), and barriers to providing clinical oncology pharmacy (third section).

Results:
Overall, 314 colleagues responded to the clinical oncology pharmacy survey from 59 individual countries in Europe, Asia, Africa, and America, yielding a response rate of 28.6%. Overall, all participants who responded to the survey reported being involved in one or more tasks associated with clinical oncology pharmacy, with the highest responses in the section's patient counseling (62.5% of participants actively counseling outpatients) and drug–drug interaction checking (performed by 58% of participants). Furthermore, almost 50% of participants indicated that their pharmaceutical interventions are always or usually accepted by doctors.

Conclusions:
This survey showed that there is currently an operational clinical oncology pharmacy service in all countries surveyed. This may provide a reference for policymakers, promote international communication, and shed light on the future development of clinical pharmacies in oncology settings. These survey findings may also help guide future education strategies for the ESOP Global and other providers of oncology pharmacy education.
Effectiveness of Transcranial Direct Current Stimulation in Knee Osteoarthritis
Authors: Wu Ssu-Hsuan , Lin Chueh-Ho , Hsu Tzu-Yun , Liou Tsan-Hon , Escorpizo Reuben , Chen Hung-Chou 
Published: July 2024

Objective
The aim of the study is to assess the effectiveness of transcranial direct current stimulation in knee osteoarthritis.

Methods
The study searched PubMed, Cochrane Library, Embase, and Scopus databases until August 3, 2023, and identified randomized controlled trials evaluating the effects of transcranial direct current stimulation in knee osteoarthritis whose outcomes using pain scores or functional scales. The selected randomized controlled trials were subjected to meta-analysis and risk of bias assessment.

Results
Seven randomized controlled trials involving 488 patients were included in this meta-analysis. Compared with the control group, the transcranial direct current stimulation group exhibited significant improvement in pain scores after treatment (standardized mean difference = 1.03; 95% confidence interval: 0.70 to 1.35; n = 359; I
2 = 46%), pain scores during follow-up (standardized mean difference = 0.83; 95% confidence interval: 0.21 to 1.45; n = 358; I
2 = 86%), and Western Ontario and McMaster Universities Osteoarthritis scores after treatment (standardized mean difference = 4.76; 95% confidence interval: 0.16 to 9.53; n = 319; I
2 = 74%), but Western Ontario and McMaster Universities Osteoarthritis scores during follow-up did not differ significantly between the groups (standardized mean difference = 0.06; 95% confidence interval: −0.2 to 0.32; n = 225; I
2 = 0%).

Conclusions
Transcranial direct current stimulation is a promising therapy for knee osteoarthritis. Further investigation using large-scale, high-quality randomized controlled trials is necessary for optimal transcranial direct current stimulation approach in knee osteoarthritis.
Gene Expression Profiles Perturbed by Injury to the Mouse Intervertebral Disc
Authors: Chen Ken , Tian Zuozhen , Wang Huan , Qin Ling , Enomoto-Iwamoto Motomi , Zhang Yejia 
Published: July 2024

Abstract

Objectives
Back pain subsequent to intervertebral disc injury is a common clinical problem. Previous work examining early molecular changes post injury mainly used a candidate marker approach. In this study, gene expression in the injured and intact mouse tail intervertebral discs was determined with a nonbiased whole transcriptome approach.

Design
Mouse tail intervertebral disc injury was induced by a needle puncture. Whole murine transcriptome was determined by RNASeq. Transcriptomes of injured intervertebral discs were compared with those of intact controls by bioinformatic methods.

Results
Among the 18,078 murine genes examined, 592 genes were differentially expressed (P.adj < 0.01). Novel genes upregulated in injured compared with intact intervertebral discs included Chl1, Lum, etc. Ontology study of upregulated genes revealed that leukocyte migration was the most enriched biological process, and network analysis showed that Tnfa had the most protein-protein interactions. Novel downregulated genes in the injured intervertebral discs included 4833412C05Rik, Myoc, etc. The most enriched downregulated pathways were related to cytoskeletal organization.

Conclusions
Novel genes highly regulated after disc injury were identified with an unbiased approach; they may serve as biomarkers of injury and response to treatments in future experiments. Enriched biological pathways and molecules with high numbers of connections may be targets for treatments after injury.
Substance Use Screening in a Large Pediatric Primary Care Network: A Quality Improvement Project
Authors: Karas Dave , Eggleston Lisa , Goldman William , Bigham Mike , White P. Cooper 
Published: July 2024

Background:
This project aimed to introduce substance use screening, using the CRAFFT (Car, Relax, Alone, Forget, Family/Friends, Trouble) screening tool, into the routine care of adolescents using quality improvement strategies and tools.

Methods:
We expanded a single-site project showing the successful introduction of CRAFFT screening into adolescent care to include the entire 34-site primary care network of a children’s hospital in Northeastern Ohio. We deployed quality improvement methodology to facilitate the acceptance and use of the screener. Data showing the percentage of eligible adolescents screened were collected and shared monthly with network providers.

Results:
The single-site phase increased the screening rate from 3.5% to 72%. The percentage screened for the network phase rose from 0% to >90% in the first 2 months of the project and remained at that level. Of those screened, 85% were low risk, 3% were medium risk, and 2% were high risk. Ten percent of the results were not recorded in a way that allowed for post hoc risk assessment. During the network phase, 35,750 of 38,427 (93%) eligible patients completed the screening form.

Conclusions:
This project resulted in the highly reliable use of the CRAFFT screener in a large primary care network.
Improving Pediatric Hypertension Screening in an Academic Primary Care Setting
Authors: Tas Vildan , Birisci Esma , Jones Rachel Achor , Forbus John J. , Blaszak Richard T. , Crawford Brendan , Ilyas Mohammad , Magee James S. , Sisterhen Laura L. 
Published: July 2024

Introduction:
Adherence to the American Academy of Pediatrics clinical practice guidelines for screening and managing high blood pressure (BP) is low. This team sought to improve recognition and documentation of relevant diagnoses in patients aged 13–20 years who presented to general pediatric clinics.

Methods:
The primary outcome measure was the proportion of office visits for patients ages 13–20 with a BP ≥ 120/80 with a visit or problem list diagnosis of hypertension or elevated BP. Secondary measures included (1) the proportion of patients who had their BP measured in the right arm, (2) the proportion of patients who had a mid-arm circumference measurement recorded, and (3) the proportion of patients who had a second BP reading measured at the visit. Interventions addressed key drivers for evidence-based high BP screening: standard BP measurement, electronic health record clinical decision support, and clinical pathway adoption. Data were collected over a twenty-seven-month period and plotted using the Laney p’ chart.

Results:
Provider documentation of elevated BP or hypertension improved from a baseline mean of 24% in April 2020 through January 2022 to 41% in February 2021 through June 2022. All secondary outcome measures also demonstrated significant improvement.

Conclusions:
This project demonstrates the feasibility of improving adherence to best practices of BP measurement in primary care clinics through education, acquisition of resources, and implementation of electronic health record flags for abnormal values.
The relationship between distortion product otoacoustic emissions and audiometric thresholds in the extended high-frequency range
Authors: Hauser Samantha N. , Hustedt-Mai Alexandra R. , Wichlinski Anna , Bharadwaj Hari M. 
Published: July 2024

ABSTRACTDistortion product otoacoustic emissions (DPOAEs) and behavioral audiometry are routinely used for hearing screening and assessment. These measures provide related information about hearing status as both are sensitive to cochlear pathologies. However, DPOAE testing is quicker and does not require a behavioral response. Despite these practical advantages, DPOAE testing is often limited to screening only low and mid- frequencies. Variation in ear canal acoustics across ears and probe placements has resulted in less reliable measurements of DPOAEs near 4 kHz and above where standing waves commonly occur. Stimulus calibration in forward pressure level and responses in emitted pressure level can reduce measurement variability. Using these calibrations, this study assessed the correlation between audiometry and DPOAEs in the extended high frequencies where stimulus calibrations and responses are most susceptible to the effect of standing waves. Behavioral thresholds and DPOAE amplitudes were negatively correlated, and DPOAE amplitudes in emitted pressure level accounted for twice as much variance as amplitudes in sound pressure level. Both measures were correlated with age. These data show that with appropriate calibration methods, extended high-frequency DPOAEs are sensitive to differences in audiometric thresholds and highlight the need to consider calibration techniques in clinical and research applications of DPOAEs.
Forest edges and other semi-natural habitat edges increase wild bee species richness and habitat connectivity in intensively managed temperate landscapes
Authors: Sydenham Markus A.K. , Nielsen Anders , Dupont Yoko L. , Rasmussen Claus , Madsen Henning B. , Torvanger Marianne S. , Star Bastiaan 
Published: July 2024

AbstractPollinator conservation schemes are typically focused on conserving existing-, restoring degraded- or establishing new wild bee habitats. The effectiveness of such conservation schemes depends on the presence of dispersal corridors that allow habitat colonization by bees. Nonetheless, we lack an understanding of the role of semi-natural habitats edges on the connectivity of pollinator communities across intensively managed landscapes. Here, we use data from wild bee communities comprising 953 occurrences from 79 species of non-parasitic bees, sampled at 68 locations distributed across a Norwegian and a Danish landscape to show that the proportion of semi-natural habitat edges is positively correlated to bee species richness and habitat connectivity. Specifically, we found that wild bee species richness sampled along roadsides increased with the proportion of semi-natural habitat edges within1.5 km of the study sites and with local plant species richness. We combined maps showing the proportion of seminatural habitat edges with least cost path analysis to find the most likely dispersal route between our bee communities. We find that these least cost path lengths provide better models of bee species compositional similarity than geographic distance (|ΔAICc| > 2), suggesting that seminatural habitat edges act as dispersal corridors in intensively managed landscapes. However, we also find that compositional similarity between communities depend on site-specific plant species richness stressing the importance of improving the habitat quality of edge habitats if they are to function as dispersal corridors. We discuss potential management options for improving wild bee habitat conditions along seminatural habitat edges and illustrate how maps of least cost paths can be used to identify dispersal corridors between pollinator habitats of conservation priority. Maps of dispersal corridors can be used to direct wild bee habitat management actions along seminatural habitat edges to facilitate the dispersal of bees between larger grassland habitats.
Resolving multi-image spatial lipidomic responses to inhaled toxicants by machine learning
Authors: Stevens Nathanial C. , Shen Tong , Martinez Joshua , Evans Veneese J. B. , Domanico Morgan C. , Neumann Elizabeth K. , Van Winkle Laura S. , Fiehn Oliver 
Published: July 2024

AbstractRegional responses to inhaled toxicants are essential to understand the pathogenesis of lung disease under exposure to air pollution. We evaluated the effect of combined allergen sensitization and ozone exposure on eliciting spatial differences in lipid distribution in the mouse lung that may contribute to ozone-induced exacerbations in asthma. Lung lobes from male and female BALB/c mice were cryosectioned and acquired by high resolution mass spectrometry imaging (MSI). Processed MSI peak annotations were validated by LC-MS/MS data from scraped tissue slides and microdissected lung tissue. Images were normalized and segmented into clusters. Interestingly, segmented clusters overlapped with stained serial tissue sections, enabling statistical analysis across biological replicates for morphologically relevant lung regions. Spatially distinct lipids had higher overall degree of unsaturated fatty acids in distal lung regions compared to proximal regions. Furthermore, the airway and alveolar epithelium exhibited significantly decreased sphingolipid and glycerophospholipid abundance in females, but not in males. We demonstrate the potential role of lipid saturation in healthy lung function and highlight sex differences in regional lung lipid distribution following ozone exposure. Our study provides a framework for future MSI experiments capable of relative quantification across biological replicates and expansion to multiple sample types, including human tissue.
Censored Least Squares for Imputing Missing Values in PARAFAC Tensor Factorization
Authors: Hung Ethan C. , Hodzic Enio , Tan Zhixin Cyrillus , Meyer Aaron S. 
Published: July 2024

AbstractTensor factorization is a dimensionality reduction method applied to multidimensional arrays. These methods are useful for identifying patterns within a variety of biomedical datasets due to their ability to preserve the organizational structure of experiments and therefore aid in generating meaningful insights. However, missing data in the datasets being analyzed can impose challenges. Tensor factorization can be performed with some level of missing data and reconstruct a complete tensor. However, while tensor methods may impute these missing values, the choice of fitting algorithm may influence the fidelity of these imputations. Previous approaches, based on alternating least squares with prefilled values or direct optimization, suffer from introduced bias or slow computational performance. In this study, we propose that censored least squares can better handle missing values with data structured in tensor form. We ran censored least squares on four different biological datasets and compared its performance against alternating least squares with prefilled values and direct optimization. We used the error of imputation and the ability to infer masked values to benchmark their missing data performance. Censored least squares appeared best suited for the analysis of high-dimensional biological data by accuracy and convergence metrics across several studies.
The West African lungfish secretes a living cocoon during aestivation with uncertain antimicrobial function
Authors: Palominos M. Fernanda , Bharadwaj Rangarajan , Tralka Charles , Trang Kenneth , Aka David , Alami Mariam , Andrews Dominique , Bartlett Ben I. , Golde Chloe , Liu Joseph , Le-Pedroza Maya , Perrot Robert , Seiter Blanca , Sparrow Claudia , Shapira Michael , Martin Christopher H. 
Published: July 2024

AbstractOne of the most exceptional adaptations to extreme drought is found in the sister group to tetrapods, the lungfishes (Dipnoi), which can aestivate inside a mucus cocoon for multiple years at reduced metabolic rates with complete cessation of ingestion and excretion. However, the function of the cocoon tissue is not fully understood. Here we developed a new more natural laboratory protocol for inducing aestivation in the West African lungfish,Protopterus annectens,and investigated the structure and function of the cocoon. We used electron microscopy and imaging of live tissue-stains to confirm that the inner and outer layers of the paper-thin cocoon are composed primarily of living cells. However, we also repeatedly observed extensive bacterial and fungal growth covering the cocoon and found no evidence of anti-microbial activity in vitro againstE. colifor the cocoon tissue in this species. This classroom discovery-based research, performed during a course-based undergraduate research experience course (CURE), provides a robust laboratory protocol for investigating aestivation and calls into the question the function of this bizarre vertebrate adaptation.
Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults
Authors: Bernal Jose , Menze Inga , Yakupov Renat , Peters Oliver , Hellmann-Regen Julian , Freiesleben Silka Dawn , Priller Josef , Spruth Eike Jakob , Altenstein Slawek , Schneider Anja , Fliessbach Klaus , Wiltfang Jens , Schott Björn H. , Jessen Frank , Rostamzadeh Ayda , Glanz Wenzel , Incesoy Enise I. , Buerger Katharina , Janowitz Daniel , Ewers Michael , Perneczky Robert , Rauchmann Boris-Stephan , Teipel Stefan , Kilimann Ingo , Laske Christoph , Sodenkamp Sebastian , Spottke Annika , Esser Anna , Lüsebrink Falk , Dechent Peter , Hetzer Stefan , Scheffler Klaus , Schreiber Stefanie , Düzel Emrah , Ziegler Gabriel 
Published: July 2024

AbstractBackgroundFor over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussions about their coupled temporal dynamics. Longitudinal studies supporting this hypothesis remain nonetheless scarce.MethodsIn this study, we applied regional and global bivariate latent growth curve modelling (BLGCM) to longitudinal data from 436 cognitively unimpaired participants (DELCODE cohort; median age 69.70 [IQR 65.44, 74.49] years; 52.98% female) to examine the extent to which WMH and cortical thickness were interrelated over a four-year period.ResultsOur findings were three-fold. First, at baseline, individuals with larger WMH volumes had lower mean cortical thicknesses over the entire brain. Second, individuals who experienced a steeper thinning of their cingulate and temporal cortices over time had larger baseline WMH volumes in the frontal, parietal, and occipital lobes. Third, individuals with thinner cortices at baseline tended to undergo faster WMH progression over four years, particularly in the occipital and parietal lobes.ConclusionsOur study suggests that cortical thinning and WMH progression could be mutually reinforcing rather than parallel, unrelated processes, which become entangled before cognitive deficits are detectable.Trial RegistrationGerman Clinical Trials Register (DRKS00007966, 04/05/2015)
miR-184 modulatesdilp8to control developmental timing during normal growth conditions and in response to developmental perturbations
Authors: Fernandes Jervis , Naseem Muhammed , MP Ayisha Marwa , Varghese Jishy 
Published: July 2024

AbstractOrganismal development depends on the precise coordination of growth and developmental timing, which is regulated by a complex interplay of intrinsic and extrinsic factors. However, the mechanisms underlying this regulation are not fully understood. Post-transcriptional regulation by microRNAs (miRNAs) plays a pivotal role in ensuring the proper timing of gene expression necessary for growth and development. In this study, we conducted a genetic screen to identify microRNAs that regulate developmental timing inDrosophila. Our screen identifiedmiR-184,previously implicated in germline maturation and embryonic development, as a regulator of pupariation timing by acting in the larval imaginal discs. Using genetic and molecular approaches, we identifiedDrosophila insulin-like peptide 8(Dilp8), a paracrine factor critical for regulating developmental stability, as a target ofmiR-184. During normal larval development miR-184 facilitates timely pupariation by regulatingdilp8levels. Furthermore, we demonstrate that miR-184 plays a critical role in tissue damage responses by inducingdilp8expression, which delays pupariation to enable damage repair mechanisms. These findings reveal a novel post-transcriptional regulatory mechanism that links miR-184 to the control of developmental timing under normal growth conditions and in response to tissue damage.