bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic obstructive pulmonary disease and cardiovascular disease: mechanistic links and implications for practice
Authors: Maeda Tetsuro , Dransfield Mark T. 
Published: December 2023

Purpose of review
Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) are both significant burdens on the healthcare system and often coexist. Mechanistic links between the two conditions and their clinical impact are increasingly understood.

Recent findings
Recent studies demonstrate multiple mechanisms by which the pathobiology of COPD may have negative effects on the cardiovascular system. These include extrapulmonary consequences of the COPD inflammatory state, cardiac autonomic dysfunction, which has been recently implicated in worsening respiratory symptoms and exacerbation risk, and mechanical effects of lung hyperinflation on left ventricular diastolic function.
Clinical studies have consistently shown a high prevalence of CVD in COPD patients and worsened outcomes (and vice versa). Exacerbations of COPD have also been demonstrated to dramatically increase the risk of cardiovascular events. While some safety concerns exist, medications for COPD and cardiovascular disease should be used in accordance with respective guidelines. However, real-world data show suboptimal management for patients with COPD and CVD.

Summary
COPD and cardiovascular disease have complicated interrelationships. Further mechanistic studies may lead to defining better targets for interventions. Education for medical professionals and implementation of novel screening protocols should be encouraged to fill in the gaps in clinical care for these patients.
Bempedoic acid: new evidence and recommendations on use
Authors: Paponja Kristina , Pećin Ivan , Reiner Željko , Banach Maciej 
Published: December 2023

Purposes of review
Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity worldwide. Recognizing the importance of dyslipidemia treatment in the prevention of cardiovascular events has become a part of standard clinical practice. Desired values of LDL cholesterol (LDL-C) have become lower and lower in the last few decades, as evidenced by the most recent guidelines. Therefore, efforts to lower LDL cholesterol concentrations with conventional therapies and combinations of lipid-lowering therapy may not be successful in a high proportion of patients.

Recent findings
Bempedoic acid is a novel agent, first in-class ATP Citrate Lyase (ACL) inhibitor, which targets biosynthesis of the cholesterol in the liver. Considering the results of phase 3 studies, it has been approved for sole use for dyslipidemia treatment for patients who are statin-intolerant or in combination with statin-ezetimibe for those suffering from familial hypercholesterolemia or ASCVD and unable to reach targeted LDL-C values.

Summary
Bempedoic acid has proven beneficial for further reduction of LDL cholesterol for targeted groups of patients. It is not only efficient but also a well tolerated, affordable, and available agent whose place in lipid-lowering management is yet to be fully understood with new data collected from ongoing clinical research. In this review we suggest the place of bempedoic acid in lipid-lowering management.
Ovarian Mesonephric-like Adenocarcinoma Recurring With a Rhabdomyosarcoma Component: A Case Report
Authors: Yamamoto Akiko , Nagai Takeshi , Sukeda Aoi , Kajiwara Manami , Fukunaga Masaharu , Sasaki Toru , Kinoshita Yuta , Hayashi Motoshige , Hayashi Shigehiro , Ono Masataka , Futagami Masayuki , Nishi Hirotaka 
Published: December 2023

Mesonephric-like adenocarcinoma (MLA) has recently been described as a tumor of the endometrium or ovaries, which, morphologically and immunohistochemically, resembles mesonephric adenocarcinoma arising mostly in the uterine cervix. Herein, we report, to our knowledge, the first case of ovarian MLA that developed into an extremely rapidly growing recurrent mesonephric-like carcinosarcoma, as confirmed by a genomic profiling test. A 51-year-old woman underwent chemotherapy with complete debulking surgery for ovarian carcinoma. Pathologically, the patient was diagnosed with stage IVB ovarian MLA. Subsequent to 15 months of complete remission, an enhanced computed tomography scan revealed a solid tumor of 10 cm diameter in the abdominal cavity. Secondary surgery was terminated with a 2 cm2 tumor biopsy specimen collection considering perioperative complications. Histologically, the tumor consisted of short spindle cells, and immunohistochemical staining revealed a rhabdomyosarcomatous profile without an epithelial component. Despite treatment for the sarcoma, she died 3 months after the detection of the tumor. The genomic profiling of the primary ovarian carcinoma and secondary resected tumor biopsy specimens revealed an identical KRAS mutation in both. Therefore, we concluded that the ovarian MLA recurred with a rhabdomyosarcoma component.
Left ventricular assist device-associated driveline infections as a specific form of complicated skin and soft tissue infection/acute bacterial skin and skin structure infection – issues and therapeutic options
Authors: Eckmann Christian , Sunderkötter Cord , Becker Karsten , Grabein Béatrice , Hagel Stefan , Hanses Frank , Wichmann Dominic , Thalhammer Florian 
Published: December 2023

Purpose of review
This review comments on the current guidelines for the treatment of wound infections under definition of acute bacterial skin and skin structure infections (ABSSSI). However, wound infections around a catheter, such as driveline infections of a left ventricular assist device (LVAD) are not specifically listed under this definition in any of the existing guidelines.

Recent findings
Definitions and classification of LVAD infections may vary across countries, and the existing guidelines and recommendations may not be equally interpreted among physicians, making it unclear if these infections can be considered as ABSSSI. Consequently, the use of certain antibiotics that are approved for ABSSSI may be considered as ‘off-label’ for LVAD infections, leading to rejection of reimbursement applications in some countries, affecting treatment strategies, and hence, patients’ outcomes. However, we believe driveline exit site infections related to LVAD can be included within the ABSSSI definition.

Summary
We argue that driveline infections meet the criteria for ABSSSI which would enlarge the ‘on-label’ antibiotic armamentarium for treating these severe infections, thereby improving the patients’ quality of life.
Fibrous Dysplasia With Atypical Bilateral Upper Extremity Pattern
Authors: Chang Amy , Franssen Nathan , Sahakyan Karine 
Published: December 2023

Abstract
Fibrous dysplasia (FD) typically presents unilaterally in the lower limbs, or in the skull, mandible, or pelvis. Bilateral presentation is rarely reported. Most cases are diagnosed in the teens with 75% of patients diagnosed before the age of 30 years. In this case, a 63-year-old woman with suspected diagnosis of malignancy was referred to 99mTc-MDP scan and found to have polyostotic FD in bilateral upper extremities. Nuclear medicine can play an important role in diagnosing FD cases with atypical presentation and help risk stratification for more aggressive transformation.
Pharmacological characterization of seven human histamine H3receptor isoforms
Authors: Gao Meichun , Dekker Mabel E. , Leurs Rob , Vischer Henry F. 
Published: December 2023

AbstractThe histamine H3receptor (H3R) regulates as a presynaptic G protein-coupled receptor the release of histamine and other neurotransmitters in the brain, and is consequently a potential therapeutic target for neuronal disorders. The human H3R encodes for seven splice variants that vary in the length of intracellular loop 3 and/or the C-terminal tail but are all able to induce heterotrimeric Giprotein signaling. The last two decades H3R drug discovery and lead optimization has been exclusively focused on the 445 amino acids-long reference isoform H3R-445.In this study, we pharmacologically characterized for the first time all seven H3R isoforms by determining their binding affinities for reference histamine H3receptor agonists and inverse agonists. The H3R-453, H3R-415, and H3R-413 isoforms display similar binding affinities for all ligands as the H3R-445. However, increased agonist binding affinities were observed for the three shorter isoforms H3R-329, H3R-365, and H3R-373, whereas inverse agonists such as the approved anti-narcolepsy drug pitolisant (Wakix®) displayed significantly decreased binding affinities for the latter two isoforms. This opposite change in binding affinity of agonist versus inverse agonists on H3R-365 and H3R-373 is associated with their higher constitutive activity in a cAMP biosensor assay as compared to the other 5 isoforms. The observed differences in pharmacology between longer and shorter H3R isoforms should be considered in future drug discovery programs.
The evidence supporting AHA guidelines on adult cardiopulmonary resuscitation (CPR)
Authors: Junedahl Emma , Lundgren Peter , Andersson Erik , Gupta Vibha , Råmunddal Truls , Rawshani Aidin , Riva Gabriel , Arnetorp Ida , Hessulf Fredrik , Herlitz Johan , Djärv Therese , Rawshani Araz 
Published: December 2023

AbstractBackgroundGuidelines for the management of cardiac arrest play a crucial role in guiding clinical decisions and care. We examined the strength and quality of evidence underlying these recommendations in order to elucidate strengths and gaps in knowledge.MethodsUsing the 2020 American Heart Association (AHA) Guidelines for Adult CPR, we subdivided all recommendations into advanced life support (ALS), basic life support (BLS), and recovery after cardiac arrest, as well as a more granular categorization by topic (i.e. the intervention or evaluation recommended). The Class of Recommendation (COR) and Level of Evidence (LOE) for each were reviewed.ResultsWe noted 254 recommendations, of which 181 were ALS, 69 were BLS, and 4 were recovery after resuscitation. In total, only 2 (0.8%) had the most robust evidence (LOE A), while 23% were at LOE B-NR(Non-Randomized), 15% at LOE B-R (Randomized), 50% at LOE C-LD (Limited Data), and 12% relied on expert opinion LOE C-EO (Expert Opinion). Despite the strength of ALS recommendations (Class 1, 2a, or 2b), none had LOE A. In BLS, no recommendations were supported by LOE A. For BLS, 74% of recommendations had LOE C (C-LD or C-EO). The evidence for specific BLS topics, such as airway management, was notably low. Among ALS topics, neurological prognostication had relatively stronger evidence. Overall, 26.1% of BLS recommendations had LOE A or B, versus 43.1% for ALS recommendations.ConclusionsThere is a strong discrepancy between the strength of recommendation and the underlying evidence in cardiac arrest guidelines. The findings underscore a pressing need for more rigorous research, particularly randomized trials.
Bridge-like lipid transfer protein family member 2 suppresses ciliogenesis
Authors: Parolek Jan , Burd Christopher G. 
Published: December 2023

AbstractBridge-like lipid transfer protein family member 2 (BLTP2) is an evolutionary conserved protein with unknown function(s). The absence of BLTP2 inDrosophila melanogasterresults in impaired cellular secretion and larval death, while in mice (Mus musculus), it causes preweaning lethality. Structural predictions propose that BLTP2 belongs to the repeating β-groove domain-containing (also called the VPS13) protein family, forming a long tube with a hydrophobic core, suggesting that it operates as a lipid transfer protein (LTP). We establishBLTP2as a negative regulator of ciliogenesis in RPE-1 cells based on a strong genetic interaction withWDR44, a gene that also suppresses ciliogenesis. Like WDR44, BLTP2 localizes to membrane contact sites involving the endoplasmic reticulum and the tubular endosome network in HeLa cells and that BLTP2 depletion enhanced ciliogenesis by serum-fed RPE-1 cells, a condition where ciliogenesis is normally suppressed. This study establishes human BLTP2 as a putative lipid transfer protein acting between tubular endosomes and ER that regulates primary cilium biogenesis.Significance statementWe show the involvement of an ER-localized bridge-like lipid transfer protein, BLTP2, in ciliogenesis and establish that BLTP2 is enriched at organelle-organelle membrane contact sites involving the endoplasmic reticulum (ER) and the tubular endosome network (TEN). These results implicate, for the first time, the involvement of bulk lipid transfer between the ER and TEN in regulating ciliogenesis.
Development and clinical validation of molecular subgrouping in medulloblastoma by targeted methylation sequencing
Authors: Srivastava Shreya , Bhaisora Kamlesh , Polavarapu Naveen Kumar , Pal Lily , Singh Shalini , Rai Neha , Lingaiah Raghavendra 
Published: December 2023

AbstractBackgroundThe WHO classification of CNS tumors confers promising prognostic value to the molecular classification of medulloblastoma (MB). Next-generation sequencing (NGS) has been the primary method employed for molecular classification through transcriptomic, genomic, or methylation profiling. However, due to cost and infrastructural needs, particularly in developing countries, we propose a relatively simple, rapid, and economical Sanger sequencing-based targeted methylation sequencing method for MB classification and prognostication.MethodsEleven epigenetic targets were amplified using optimized primers and bisulfite-converted DNA for Sanger sequencing. Chromas software was used for low-quality data trimming and NCBI’s Needleman Wunsch alignment tool was used for sequence alignment to reference. The developed method was applied to tissues from twelve cases of medulloblastoma.ResultsSuccessful interpretation of methylation status in ten out of eleven targets was achieved which was sufficient for classification according to the latest WHO classification of Medulloblastoma tumors. Twelve medulloblastoma cases were classified into WNT (n=2), Group 3 (n=5), and Group 4 (n=5).ConclusionThe developed Sanger sequencing method is a cost-effective, in-house solution that can be used for molecular subgrouping of medulloblastoma. It offers an alternative to NGS, can be done on a case-to-case basis, and does not require high-end infrastructure, sample pooling, or extensive bioinformatics knowledge.Impact statementMolecular classification is imperative for determining the prognosis of medulloblastoma and is recommended by WHO. However, NGS proves to be an expensive option in developing countries. This study has come up with an affordable targeted methylation Sanger sequencing method requiring minimal bioinformatic skills, by utilizing epigenetic targets, for prognostication and risk stratification in medulloblastoma patients. The molecular subgroups of all recruited cases were successfully determined according to WHO classification which is crucial information that, when combined with clinical findings, will enable the clinicians to determine effective treatment strategies.
Utility of Cerebrospinal Fluid Protein Levels as a Potential Predictive Biomarker of Disease Severity in HIV-Associated Cryptococcal Meningitis
Authors: Kasibante John , Irfanullah Eesha , Wele Abduljewad , Okafor Elizabeth , Ssebambulidde Kenneth , Okurut Samuel , Kagimu Enock , Gakuru Jane , Rutakingirwa Morris K. , Mugabi Timothy , Nuwagira Edwin , Jjunju Samuel , Mpoza Edward , Tugume Lillian , Nsangi Laura , Musibire Abdu K , Muzoora Conrad , Rhein Joshua , Meya David B. , Boulware David R. , Abassi Mahsa 
Published: December 2023

AbstractBackgroundCerebrospinal fluid (CSF) protein levels exhibit high variability in HIV-associated cryptococcal meningitis from being normal to markedly elevated. However, the clinical implications of CSF protein levels in cryptococcal meningitis remain unclear.MethodsWe analysed data from 890 adults with HIV-associated cryptococcal meningitis randomized into two clinical trials in Uganda between 2015 and 2021. CSF protein was grouped into ≥100 mg/dL (n=249) and <100 mg/dL (n=641). We described baseline clinical variables and mortality by CSF protein levels.ResultsApproximately one-third of individuals had a baseline CSF protein ≥100 mg/dL. Those with CSF protein ≥100 mg/dL were more likely to present with Glasgow coma scale scores <15 (P<0.01), self-reported seizures at baseline (P=0.02), higher CD4 T-cells (p<0.001), and higher CSF white cells (p<0.001). Moreover, those with a baseline CSF protein ≥100 mg/dL also had a lower baseline CSF fungal burden (p<0.001) and a higher percentage of sterile CSF cultures at day 14 (p=0.02). Individuals with CSF protein ≥100 mg/dL demonstrated a more pronounced immune response consisting of upregulation of immune effector molecules pro-inflammatory cytokines, type-1 T-helper cell cytokines, type-3 chemokines, and immune-exhaustion marker (p<0.05). 18-week mortality risk in individuals with a CSF protein <100 mg/dL was 34% higher, (unadjusted Hazard Ratio 1.34; 95% CI, 1.05 to 1.70; p=0.02) than those with ≥100 mg/dL.ConclusionIn cryptococcal meningitis, individuals with CSF protein ≥100 mg/dL more frequently presented with seizures, altered mental status, immune activation, and favourable fungal outcomes. Baseline CSF protein levels may serve as a surrogate marker of immune activation and prognosis.
Improving dictionary-based named entity recognition with deep learning
Authors: Nastou Katerina , Koutrouli Mikaela , Pyysalo Sampo , Jensen Lars Juhl 
Published: December 2023

AbstractMotivationDictionary-based named entity recognition (NER) allows terms to be detected in a corpus and normalized to biomedical databases and ontologies. However, adaptation to different entity types requires new high-quality dictionaries and associated lists of blocked names for each type. The latter are so far created by identifying cases that cause many false positives through manual inspection of individual names, a process that scales poorly.ResultsIn this work we aim to improve block lists by automatically identifying names to block, based on the context in which they appear. By comparing results of three well-established biomedical NER methods, we generated a dataset of over 12.5 million text spans where the methods agree on the boundaries and type of entity tagged. These were used to generate positive and negative examples of contexts for four entity types (genes, diseases, species, chemicals), which were used to train a Transformer-based model (BioBERT) to perform entity type classification. Application of the best model (F1-score=96.7%) allowed us to generate a list of problematic names that should be blocked. Introducing this into our system doubled the size of the previous list of corpus-wide blocked names. Additionally, we generated a document-specific list that allows ambiguous names to be blocked in specific documents. These changes boosted text mining precision by∼5.5% on average, and over 8.5% for chemical and 7.5% for gene names, positively affecting several biological databases utilizing this NER system, like the STRING database, with only a minor drop in recall (0.6%).AvailabilityAll resources are available through Zenodohttps://doi.org/10.5281/zenodo.10800530and GitHubhttps://doi.org/10.5281/zenodo.10289360.
Mechano-chemical Insights in Diabetic Kidney Disease through 3D Pathotypic Model of Mesangium
Authors: Ghosh Biswajoy , Fenton Kristin Andreassen , Agarwal Krishna 
Published: December 2023

ABSTRACTThe mesangium is a crucial microenvironment in the kidney. It consists of mesangial cells and extracellular matrix that lends structural integrity to the glomerulus and aids renal filtration. The mesangial cells function in a delicate balance of matrix mechanics and chemical cues to engage in matrix formation, cell interactions, and cytokine production. Irregularities such as diabetes disturb this delicate balance leading to declining kidney function and kidney failure. While chemical and molecular studies on mesangium during diabetic kidney disease (DKD) are abundant, little is known about how the changing matrix mechanics affect the mesangial function. Here we demonstrate the co-stimulatory effects of chemical cues and matrix properties within the mesangial niche afflicted with DKD. To avail control of both mechanical and chemical parameters typical of DKD, we used photo-cured gelatin methacryloyl hydrogels to emulate mesangium in different disease stages. We simulated soft and stiff matrices to mechanically match mesangium in healthy and long-term DKD with fibrosis conditions. The mechanical properties play a dominant role over chemical factors inα−smooth muscle actin formation. This coincided with a reduction in mesangial cell processes and motility, crucial for cell interactions. The fibrotic matrix also profoundly influences collagen IV expression, potentially resulting in a thickened renal basement membrane around capillaries, reducing renal filtration efficiency. The study implies that the mechano-chemical dual input in late-stage DKD causes an accelerated decline in glomerular function. The finding consolidates viable reasoning for therapeutic challenges in late-stage kidney disease and directs future studies to find the missing pieces in understanding kidney disease through such in-vitro pathotypic models.
Beneficial ‘inefficiencies’ of western ranching: Flood-irrigated hay production sustains wetland systems by mimicking historic hydrologic processes
Authors: Donnelly J. Patrick , Jensco Kelsey , Kimball John S. , Ketchum David , Collins Daniel P. , Naugle David E. 
Published: December 2023

AbstractRanching in the American West has long relied on riparian ecosystems to grow grass-hay to feed livestock in winter and during drought. Producers seasonally flood grasslands for hay production using stream diversions and low-tech flood-irrigation on riparian floodplains. Inundation mimics natural processes that sustain riparian vegetation and recharge groundwater. The recent doubling in use of more efficient irrigation approaches, such as center-pivot sprinklers, threatens to accelerate climate change impacts by unintentionally decoupling more inefficient, traditional practices that sustain riparian systems. To address this information gap, we developed an exhaustive spatial inventory of grass-hay production and combined it with monthly surface water distributions modeled from satellite data. Surface water data were classified by wetland hydroperiod and used to estimate the proportion of wetlands supported by grass-hay production in the Intermountain West, USA. Elevation and proportion of grass-hay relative to other irrigated lands were enumerated to examine differences in their positions and abundance within landscapes. Lastly, we overlaid the delineated grass-hay wetlands with LANDFIRE pre-Euro-American Settings layer to quantify the efficacy of flood irrigation in mimicking the conservation of historical riparian processes. Findings suggest that inefficient grass-hay irrigation mirrored the timing of natural hydrology, concentrating ∼93% of flooded grasslands in historical riparian ecosystems, affirming that at large scales, this ranching practice, in part, mimics floodplain processes sustaining wetlands and groundwater recharge. Despite representing only 2.5% of irrigated lands, grass-hay operations supported a majority (58%)of temporary wetlands, a rare and declining habitat for wildlife in the Intermountain West. Tolerance for colder temperatures confined grass-hay production to upper watershed reaches where higher value crops are constrained by growing degree days. This novel understanding of grass-hay agroecology highlights the vital role of working ranches in the resilience and stewardship of riparian systems.