bluuebunny/crossref_metadata_2025_split huggingface dataset:
Web-based cognitive assessment in older adults: Where do we stand?
Authors: Belleville Sylvie , LaPlume Annalise Aleta , Purkart Rudy 
Published: August 2023

Purpose of review
The use of digital tools for remote cognitive measurement of older adults is generating increasing interest due to the numerous advantages offered for accessibility and scalability. However, these tools also pose distinctive challenges, necessitating a thorough analysis of their psychometric properties, feasibility and acceptability.

Recent findings
In this narrative review, we present the recent literature on the use of web-based cognitive assessment to characterize cognition in older adults and to contribute to the diagnosis of age-related neurodegenerative diseases. We present and discuss three types of web-based cognitive assessments: conventional cognitive tests administered through videoconferencing; unsupervised web-based assessments conducted on a computer; and unsupervised web-based assessments performed on smartphones.

Summary
There have been considerable progress documenting the properties, strengths and limitations of web-based cognitive assessments. For the three types of assessments reported here, the findings support their promising potential for older adults. However, certain aspects, such as the construct validity of these tools and the development of robust norms, remain less well documented. Nonetheless, the beneficial potential of these tools, and their current validation and feasibility data, justify their application [see Supplementary Digital Content (SDC), http://links.lww.com/CONR/A69].
A Case of Bing–Neel Syndrome Presenting Like Giant Cell Arteritis
Authors: Hepschke Jenny L. , Ramalingam Satheesh , Pohl Ute , Amel-Kashipaz Rasoul M. , Blanch Richard J. 
Published: August 2023

Abstract:
A 55-year-old woman presented with new-onset headache, scalp tenderness, shoulder arthralgias, night sweats, and loss of appetite. She was diagnosed with giant cell arteritis by her primary care physician and commenced on oral corticosteroids. However, her headache, scalp tenderness, and night sweats persisted. She then developed right Horner syndrome and trigeminal hypoesthesia. Extensive blood work-up revealed mildly elevated inflammatory markers and a paraproteinemia. Subsequent bone marrow biopsy showed lymphoplasmacytic lymphoma, with 10% of hemopoiesis, and staging led to the diagnosis of Waldenstrom macroglobulinemia without nodal or central nervous system (CNS) lesions. Immunohistochemical staining of a temporal artery biopsy showed perivascular lymphoplasmacytic cells and paraprotein deposits. She was diagnosed with CNS involvement of her macroglobulinemia—Bing–Neel syndrome (BNS). Identification of rare CNS involvement of lymphoma is challenging when a patient is already on steroid immunosuppression. In the absence of clear diagnostic criteria, the rare and heterogenous BNS remains a clinical diagnosis.
PEPhub: a database, web interface, and API for editing, sharing, and validating biological sample metadata
Authors: LeRoy Nathan J. , Khoroshevskyi Oleksandr , O’Brien Aaron , Stepień Rafał , Arslan Alip , Sheffield Nathan C. 
Published: August 2023

BackgroundAs biological data increases, we need additional infrastructure to share it and promote interoperability. While major effort has been put into sharing data, relatively less emphasis is placed on sharing metadata. Yet, sharing metadata is also important, and in some ways has a wider scope than sharing data itself.ResultsHere, we present PEPhub, an approach to improve sharing and interoperability of biological metadata. PEPhub provides an API, natural language search, and user-friendly web-based sharing and editing of sample metadata tables. We used PEPhub to process more than 100,000 published biological research projects and index them with fast semantic natural language search. PEPhub thus provides a fast and user-friendly way to finding existing biological research data, or to share new data.Availabilityhttps://pephub.databio.org
JQ1 Epigenetic Modulation of Pancreatic β-Cells (INS-1) Normalizes Glucose Sensitivity under Hyperglycemia: Therapeutic Preventive Implications for Type II Diabetes Mellitus
Authors: Hernández Mateo H. , Uçar Nazlı , Deeney Jude T. 
Published: August 2023

AbstractChronic hyperinsulinemia and insulin resistance are prequels to type II diabetes mellitus (T2D), a disease that affects over 10% of Americans and is closely associated with obesity, as nearly 90% of diabetic patients are overweight or obese. Chronic excess nutrient exposure leads to glucolipotoxicity in pancreatic β-cells, which is characterized by a left shift in glucose concentration-dependent insulin secretion. Previous studies from our laboratory have demonstrated that the Bromodomain and Extra-Terminal (BET) protein inhibitor JQ1 (400 nM) increases fatty acid (FA) oxidation in clonal pancreatic β-cells (INS-1), leading to a partial reversal of glucolipotoxicity. The present research investigates the effect of JQ1 on the glucose sensitivity of INS-1 cells under hyperglycemic conditions. INS-1 cells were pre-treated with dimethyl sulfoxide-based 400 nM JQ1 for 3 days and cultured for 5 days in RPMI 1640 media (11 mM glucose). Subsequently, INS-1 cells were pre-incubated in a modified Krebs-Henseleit buffer (1 mM glucose) before adding test solutions (1-12 mM glucose). Samples for insulin release and cellular content were measured using a Homogeneous Time-Resolved Fluorescence insulin assay kit. Insulin secretion from INS-1 cells cultured in 11 mM glucose was maximally stimulated at 4 mM glucose. Treatment with JQ1 for one day right-shifted maximal glucose-stimulated insulin secretion (GSIS) to 6 mM glucose compared to control but did not prevent stimulated insulin secretion at 4 mM glucose. Three-day treatment with JQ1 reduced secretion at 4 mM glucose to basal level (1 mM) while maintaining the right-shifted concentration-dependent GSIS, an effect described herein for the first time. Total insulin content (TIC) and release as its percentage were also measured, indicating a higher TIC and lower percentage use in JQ1-treated cells. Additionally, lipid concentration was photographically fluorescent analyzed, showing significant depletion of lipid droplets in JQ1-treated cells. Results imply that epigenetic modulation of pancreatic β-cells with JQ1 beneficially alters signal transduction pathways that maintain insulin-glucose homeostasis by ameliorating glucolipotoxicity through the preservation of a low GSIS basal level, increment of GSIS maximum capacity, delay of GSIS cuspid level at 12 mM glucose, more efficient spend of total insulin content resources, and diminished lipid accumulation due to increased FA oxidation—thereby suggesting JQ1 returning hyperglycemic β-cells to physiological conditions. Suggested future directions include improving the efficacy and accuracy of JQ1 and similar small-molecule BET inhibitors through tests in human subjects’ isolated islets, as this presents an innovative course of research for the prevention of T2D and comorbidities.
A reproducible and generalizable software workflow for analysis of large-scale neuroimaging data collections using BIDS Apps
Authors: Zhao Chenying , Jarecka Dorota , Covitz Sydney , Chen Yibei , Eickhoff Simon B. , Fair Damien A. , Franco Alexandre R. , Halchenko Yaroslav O. , Hendrickson Timothy J. , Hoffstaedter Felix , Houghton Audrey , Kiar Gregory , Macdonald Austin , Mehta Kahini , Milham Michael P. , Salo Taylor , Hanke Michael , Ghosh Satrajit S. , Cieslak Matthew , Satterthwaite Theodore D. 
Published: August 2023

ABSTRACTNeuroimaging research faces a crisis of reproducibility. With massive sample sizes and greater data complexity, this problem becomes more acute. Software that operates on imaging data defined using the Brain Imaging Data Structure (BIDS) – BIDS Apps – have provided a substantial advance. However, even using BIDS Apps, a full audit trail of data processing is a necessary prerequisite for fully reproducible research. Obtaining a faithful record of the audit trail is challenging – especially for large datasets. Recently, the FAIRly big framework was introduced as a way to facilitate reproducible processing of large-scale data by leveraging DataLad – a version control system for data management. However, the current implementation of this framework was more of a proof of concept, and could not be immediately reused by other investigators for different use cases. Here we introduce theBIDSAppBootstrap (BABS), a user-friendly and generalizable Python package for reproducible image processing at scale. BABS facilitates the reproducible application of BIDS Apps to large-scale datasets. Leveraging DataLad and the FAIRly big framework, BABS tracks the full audit trail of data processing in a scalable way by automatically preparing all scripts necessary for data processing and version tracking on high performance computing (HPC) systems. Currently, BABS supports jobs submissions and audits on Sun Grid Engine (SGE) and Slurm HPCs with a parsimonious set of programs. To demonstrate its scalability, we applied BABS to data from the Healthy Brain Network (HBN; n=2,565). Taken together, BABS allows reproducible and scalable image processing and is broadly extensible via an open-source development model.
Direct RNA-binding by MYCN mediates feedback from RNA processing to transcription control
Authors: Papadopoulos Dimitrios , Ha Stefanie Anh , Fleischhauer Daniel , Uhl Leonie , Schneider Katharina , Mikicic Ivan , Russell Timothy J. , Brem Annika , Valanju Omkar Rajendra , Gallant Peter , Schuelein-Voelk Christina , Maric Hans Michael , Beli Petra , Büchel Gabriele , Vos Seychelle M. , Eilers Martin 
Published: August 2023

AbstractThe MYCN oncoprotein broadly binds active promoters in a heterodimer with its partner protein MAX. MYCN also interacts with the nuclear exosome, a 3’-5’ exoribonuclease complex, suggesting a function in RNA metabolism. Here we show that MYCN forms stable high molecular weight complexes with the exosome and multiple RNA-binding proteins. In cells, MYCN binds to thousands of intronic RNAs; recombinant MYCN directly binds RNA via a short, highly conserved sequence termed MYCBoxI. Perturbing exosome function results in global re-localization of MYCN from promoters to intronic RNAs. At promoters, MYCN is then replaced by the MNT(MXD6) repressor protein, which inhibits MYCN-dependent transcription. MYCN promotes the degradation of its bound introns via the nuclear exosome targeting (NEXT) complex. Our data demonstrate that MYCN is an RNA-binding protein that regulates nascent transcript turnover and show that competition between its RNA– and DNA-bound states links the dynamics of the MYCN/MAX/MXD network to mRNA processing.
Single cell multi-omics analysis of chronic myeloid leukemia links cellular heterogeneity to therapy response
Authors: Warfvinge Rebecca , Ulfsson Linda Geironson , Dhapola Parashar , Safi Fatemeh , Sommarin Mikael N.E. , Soneji Shamit , Hjorth-Hansen Henrik , Mustjoki Satu , Richter Johan , Thakur Ram Krishna , Karlsson Göran 
Published: August 2023

AbstractThe advent of tyrosine kinase inhibitors (TKIs) as treatment of chronic myeloid leukemia (CML) is a paradigm in molecularly targeted cancer therapy. Nonetheless, TKI insensitive leukemia stem cells (LSCs) persist in most patients even after years of treatment. The sustained presence, heterogeneity and evolvability of LSCs are imperative for disease progression as well as recurrence during treatment-free remission (TFR). However, dynamic changes among LSC sub-populations upon TKI therapy impede their measurement and targeting. Here, we used cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to generate high-resolution single cell multiomics maps from CML patients at diagnosis, retrospectively stratified by BCR::ABL1IS(%) following 12 months of TKI therapy as per European LeukemiaNet (ELN) recommendations. Simultaneous measurement of global gene expression profiles together with >40 surface markers from the same cells revealed that each patient harbored a unique composition of stem and progenitor cells at diagnosis demonstrating that cellular heterogeneity is a hallmark of CML. The patients with treatment failure after 12 months of therapy had markedly higher abundance of molecularly defined primitive cells at diagnosis compared to the optimal responders. Furthermore, deconvolution of an independent dataset of CML patient-derived bulk transcriptomes (n=59) into constituent cell populations showed that the proportion of primitive cells versus lineage primed sub-populations significantly connected with the TKI-treatment outcome. The multiomic feature landscape enabled visualization of the primitive fraction as a heterogenous mixture of molecularly distinct Lin−CD34+CD38−/lowBCR::ABL1+LSCs and BCR::ABL1−hematopoietic stem cells (HSCs) in variable ratio across patients and guided their prospective isolation by a combination of CD26 and CD35 cell surface markers. We for the first time show that BCR::ABL1+LSCs and BCR::ABL1−HSCs can be distinctly separated as CD26+CD35−and CD26−CD35+respectively. In addition, we found the relative proportion of CD26−CD35+HSCs to be higher in optimal responders when compared to treatment failures, at diagnosis as well as following 3 months of TKI therapy, and that the LSC/HSC ratio was increased in patients with prospective treatment failure. Collectively, the patient-specific cellular heterogeneity multiomics maps build a framework towards understanding therapy response and adapting treatment by devising strategies that either extinguish TKI-insensitive LSCs or engage the immune effectors to suppress the residual leukemogenic cells.
TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype and is associated with increased survival in cancer patients with high tumor macrophage content
Authors: Gunalp Sinem , Helvacı Derya Goksu , Oner Aysenur , Bursalı Ahmet , Conforte Alessandra , Güner Hüseyin , Karakülah Gökhan , Szegezdi Eva , Sag Duygu 
Published: August 2023

ABSTRACTBackgroundTNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can either induce cell death or activate survival pathways after binding to death receptors (DRs) DR4 or DR5. TRAIL is investigated as a therapeutic agent in clinical trials due to its selective toxicity to transformed cells.Macrophages can be polarized into pro-inflammatory/tumor-fighting M1 macrophages or anti-inflammatory/tumor-supportive M2 macrophages and an inbalance between M1 and M2 macrophages can promote diseases. Therefore, identifying modulators that regulate macrophage polarization is important to design effective macrophage-targeted immunotherapies. The impact of TRAIL on macrophage polarization is not known.MethodsPrimary human monocyte-derived macrophages were pre-treated with either TRAIL or with DR4 or DR5-specific ligands and then polarized into M1, M2a, or M2c phenotypesin vitro. The expression of M1 and M2 markers in macrophage subtypes was analyzed by RNA sequencing, qPCR, ELISA, and flow cytometry. Furthermore, the cytotoxicity of the macrophages against U937 AML tumor targets was assessed by flow cytometry. TCGA datasets were also analyzed to correlate TRAIL with M1/M2 markers, and the overall survival of cancer patients.ResultsTRAIL increased the expression of M1 markers at both mRNA and protein levels while decreasing the expression of M2 markers at the mRNA level in human macrophages. TRAIL also shifted M2 macrophages towards an M1 phenotype. Our data showed that both DR4 and DR5 death receptors play a role in macrophage polarization. Furthermore, TRAIL enhanced the cytotoxicity of macrophages against the AML cancer cellsin vitro. Finally, TRAIL expression was positively correlated with increased expression of M1 markers in the tumors from ovarian and sarcoma cancer patients and longer overall survival in cases with high, but not low, tumor macrophage content.ConclusionsTRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype via both DR4 and DR5. Our study defines TRAIL as a new regulator of macrophage polarization and suggests that targeting DRs can enhance the anti-tumorigenic response of macrophages in the tumor microenvironment by increasing M1 polarization.
Development of an optimized, non-stem cell line for intranasal delivery of therapeutic cargo to the central nervous system
Authors: El-Ayoubi Ali , Arakelyan Arsen , Klawitter Moritz , Merk Luisa , Hakobyan Siras , Gonzalez-Menendez Irene , Quintanilla-Fend Leticia , Holm Per Sonne , Mikulits Wolfgang , Schwab Matthias , Danielyan Lusine , Naumann Ulrike 
Published: August 2023

AbstractNeural stem cells (NSC) are considered to be valuable candidates for delivering a variety of anti-cancer agents to brain tumors, including oncolytic viruses. However, owing to the previously reported tumorigenic potential of NSC cell line after intranasal administration (INA), here we identified the human hepatic stellate cell line (LX-2) as a cell type capable of longer resistance to replication of oncolytic adenoviruses (OAV) as therapeutic cargo, and being non-tumorigenic after INA. Our data show that LX-2 cells can longer withstand the OAV XVir-N-31 replication and oncolysis than NSCs. By selecting the highly migratory cell population out of LX-2, an offspring cell line with a higher and more stable capability to migrate was generated. Additionally, as a safety backup, we applied genomic HSV-TK integration into LX-2 leading to the high vulnerability to Ganciclovir. Histopathological analyses confirmed the absence of neoplasia in the respiratory tracts and brains of immuno-compromised mice 3 months after INA of LX-2 cells. Our data suggest that LX-2 is a novel robust and safe cell line for delivering anti-cancer and other therapeutic agents to the brain.
A Hybrid Transistor with Transcriptionally Controlled Computation and Plasticity
Authors: Gao Yang , Zhou Yuchen , Ji Xudong , Graham Austin J. , Dundas Christopher M. , Mahfoud Ismar E. Miniel , Tibbett Bailey M. , Tan Benjamin , Partipilo Gina , Dodabalapur Ananth , Rivnay Jonathan , Keitz Benjamin K. 
Published: August 2023

AbstractOrganic electrochemical transistors (OECTs) are ideal devices for translating biological signals into electrical readouts and have applications in bioelectronics, biosensing, and neuromorphic computing. Despite their potential, developing programmable and modular methods for living systems to interface with OECTs has proven challenging. Here we describe hybrid OECTs containing the model electroactive bacteriumShewanella oneidensisthat enable the transduction of biological computations to electrical responses. Specifically, we fabricated planar p-type OECTs and demonstrated that channel de-doping is driven by extracellular electron transfer (EET) fromS. oneidensis. Leveraging this mechanistic understanding and our ability to control EET flux via transcriptional regulation, we used plasmid-based Boolean logic gates to translate biological computation into current changes within the OECT. Finally, we demonstrated EET-driven changes to OECT synaptic plasticity. This work enables fundamental EET studies and OECT- based biosensing and biocomputing systems with genetically controllable and modular design elements.
Texans support mountain lion conservation management
Authors: Ohrens Omar , Ghasemi Benjamin , Gulas-Wroblewski Bonnie E. , Elbroch L. Mark 
Published: August 2023

AbstractThe state of Texas encompasses an estimated 7% of the United States mountain lion (Puma concolor) population, a likely overestimate due to their nongame status, unregulated take and high mountain lion mortality rates. In August 2022, Texas Parks and Wildlife Department (TPWD) denied a petition to amend state mountain lion management policies, but was mandated by the Texas Wildlife Commission to form a stakeholder group to assess the potential to initiate mountain lion management and policy. Herein, we synthesize survey data collected and previously published in a report by Ghasemi et al. (2022) to provide members of this mountain lion stakeholder working group, the Commission, and TPWD with succinct summaries of Texas residents’ knowledge and attitudes salient to the evaluation of mountain lion management in the state. We analyzed responses to represent the opinion of all Texans as well as to compare the sentiments of four key stakeholder groups: hunters vs. nonhunters; livestock owners vs. people without livestock; urban vs. rural residents; and Hispanics vs. non-Hispanics. Overall, Texans expressed a positive sentiment about mountain lions and supported management to conserve the species. Respondents exhibited very high consensus regarding the value of scientific research about mountain lions and expressed overwhelming support for mandatory reporting of any mountain lion killed for any purpose by hunters, trappers, or state or federal agents. Texas residents also backed a compensation program supporting livestock producers who lose animals to mountain lions and rapid checking of set traps. Contrary to expectation, hunters and livestock owners were more positive about mountain lions than non-hunters and people without livestock, and we detected no differences in the responses of urban versus rural residents or Hispanics versus non-Hispanics on any topic.
Metacognition and Problem Solving: How Self-Coaching Helps First-Year Students Move Past the Discomfort of Monitoring
Authors: Halmo Stephanie M. , Yamini Kira A. , Stanton Julie Dangremond 
Published: August 2023

ABSTRACTStronger metacognitive regulation skills are linked to increased academic achievement. Metacognition has primarily been studied using retrospective methods, but these methods limit access to students’ in-the-moment metacognition. We investigated first-year life science students’ in-the-moment metacognition while they solved challenging problems, and asked 1) What metacognitive regulation skills are evident when first-year life science students solve problems on their own? and 2) What aspects of learning self-efficacy do first-year life science students reveal when they solve problems on their own? Think aloud interviews were conducted with 52 first-year life science students across three institutions and analyzed using qualitative content analysis. Our results reveal that first-year life science students use an array of monitoring and evaluating skills while solving problems, which challenges the deficit-oriented notion that students enter college with poor metacognitive skills. Additionally, a handful of students self-coached or encouraged themselves as they confronted aspects of the problems that were unfamiliar. These verbalizations suggest ways we can encourage students to couple their metacognitive regulation skills and self-efficacy to persist when faced with challenging disciplinary problems. Based on our findings, we offer recommendations for how instructors can help first-year life science students develop and strengthen their metacognition to achieve improved problem-solving performance.