bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Assessment of Risk-Based Quality Management Adoption in Clinical Trials
Authors: Dirks Abigail , Florez Maria , Torche Francois , Young Steve , Slizgi Brian , Getz Kenneth 
Published: February 2024

Abstract
Background
Risk-based monitoring (RBM) and risk-based quality management (RBQM) offer a compelling approach to increase efficiency, speed and quality in clinical trials by prioritizing and mitigating risks related to essential safety and efficacy data. Since 2013, the FDA and EMA have encouraged the use of RBM/RBQM, however adoption has been slow with limited understanding of the barriers to adoption.

Methods
The Tufts Center for the Study of Drug Development conducted an online survey among pharmaceutical, biotechnology, and contract research organizations and gathered 206 responses on 32 distinct RBQM practices.

Results
On average, companies implemented RBQM in 57% of their clinical trials. Lower levels of adoption were observed among companies conducting fewer than 25 trials annually (48%) compared to those conducting more than 100 trials annually (63%). Primary barriers to adoption include lack of organizational knowledge and awareness, mixed perceptions of the value proposition of RBQM, and poor change management planning and execution. Insights into improving the level of adoption are discussed.
Mental health challenges in Nigeria: Bridging the gap between demand and resources
Authors: Fadele Kehinde Precious , Igwe Stephen Chukwuemeka , Toluwalogo Niji-Olawepo , Udokang Ephraim Ikpongifono , Ogaya Jerico B. , Lucero-Prisno Don Eliseo 
Published: February 2024

Abstract
This study discusses the significant topic of mental health challenges in Nigeria, focusing on the shortage of mental health professionals, particularly psychiatrists, and the factors influencing medical students’ hesitation to pursue psychiatry as a career path. We examine the multifaceted difficulties in Nigeria’s mental health environment using various sources, including research studies and statistical data. The scarcity of psychiatrists, with only 250 for a population of 200 million, underscores the urgent need for attention to mental health within the country. Factors such as brain drain, inadequate learning infrastructure, limited research exposure and insufficient health coverage contribute to this crisis. Additionally, societal stigma and financial constraints discourage students from pursuing psychiatry as a career. To address these challenges comprehensively, we propose a holistic approach that involves cross-disciplinary collaboration, robust mental health education in all healthcare programs, community-based awareness initiatives and transdisciplinary teamwork among mental health providers. We highlight the importance of mentorship, scholarships and national advocacy to encourage more individuals to enter the mental health profession, emphasizing the need for diversity and inclusiveness. Furthermore, our paper stresses the significance of research and innovation in advancing mental health treatment and inspiring passion for mental health among students and aspiring professionals. By embracing this comprehensive set of recommendations, we aim to cultivate a diverse, talented and compassionate workforce capable of effectively addressing Nigeria’s pressing mental health challenges.
Puzzle-shaped cells and the mechanical response of tobacco (Nicotiana tabacum L.) seed coats
Authors: Bonfanti Silvia , Beretta Mario , Milan Simone , Ferrario Cinzia , Biffi Carlo Alberto , Chepizhko Oleksandr , La Porta Caterina A. M. , Tuissi Ausonio , Zapperi Stefano 
Published: February 2024

Abstract
The seed coat of tobacco displays an intriguing cellular pattern characterised by puzzle-like shapes whose specific function is unknown. Here, we perform a detailed investigation of the structure of tobacco seeds by electron microscopy and then follow the germination process by time lapse optical microscopy. We use particle image velocimetry to reveal the local deformation fields and perform compression experiments to study the mechanical properties of the seeds as a function of their hydration. To understand the mechanical role of the observed coat structure, we perform finite element calculations comparing structure with puzzle-shaped cells with similar structures lacking re-entrant features. The results indicate that puzzle-shaped cells act as stress suppressors and reduce the Poisson’s ratio of the seed coat structure. We thus conclude that the peculiar cellular structure of these seed coats serves a mechanical purpose that could be relevant to control germination.
Intramammary treatment of clinical mastitis quarters with ceftiofur does not cause anbiotic residues in adjacent untreated quarters
Authors: Carvalho André Luis Mendes Azevedo , Nascimento Neto José da Páscoa , Carvalho Túlio Bastos Tomaz , Lima Neto Hélio Rezende , Victali Rafael Morgado , Chalfun Luthesco Haddad Lima 
Published: February 2024

AbstractThe study was carried out in dairy cows to elucidate whether treatment of clinical mastitis quarters with Spectramast® LC (ceftiofur hydrochloride, 125 mg, Zoetis) created a reason for discarding milk from adjacent untreated healthy quarters. The antibiotic was infused once daily in the affected mammary quarter for four days. Forty-nine cows were evaluated after diagnosis of clinical mastitis in three or fewer udder quarters. In all cases, quarters that did not receive treatment had milk samples collected one day after the end of treatment. All milk samples from untreated quarters were below the maximum permissible limit for the presence of antibiotic residues after analysis with the BetaStar S Combo test. Pharmacokinetic and pharmacodynamic characteristics may explain this finding. We conclude that it is feasible to use milk from untreated quarters of animals that have been treated with Spectramast® LC. We also reiterate the need to carry out tests with other pharmacological bases, and that the results found in this experiment cannot be extrapolated to other drugs.Dairy cattle have considerable importance in the development of the Brazilian economy, being directly linked to economic and social progress. In the first half of 2020, 12.1 billion liters of milk were produced in Brazil and in 2019, there was a new record of 25.01 billion liters produced (IBGE, 2020). This production comes from a wide variety of production systems, coming from smallholder farmers as well as from large companies that use the latest technologies available on the market. Dairy production is a complex activity. For one to obtain economical success, several aspects must be monitored. Maintaining the health of animals is a top priority, and the literature suggests that various diseases are a common challenge for dairy producers. Mastitis is the main disease that affects dairy cows, responsible for considerable economic loss and significant zootechnical and productive challenges (Ruegg, 2017). It is considered the second leading cause of cow culling in dairy herds, behind reproductive problems. Mastitis is characterized by infection of the mammary gland and may or may not occur with inflammation, generating changes in the mammary tissue and properties of the milk. It is classifield into clinical or subclinical mastitis, according to presence or absence of clinical signs, and into contagious or environmental based on the causative agent (Correa et al., 2001).
Analyzing the multi-state system under a run shock model
Authors: Ozkut Murat , Kan Cihangir , Franko Ceki 
Published: February 2024

AbstractA system experiences random shocks over time, with two critical levels, d1 and d2, where $d_{1} \lt d_{2}$. k consecutive shocks with magnitudes between d1 and d2 partially damaging the system, causing it to transition to a lower, partially working state. Shocks with magnitudes above d2 have a catastrophic effect, resulting in complete failure. This theoretical framework gives rise to a multi-state system characterized by an indeterminate quantity of states. When the time between successive shocks follows a phase-type distribution, a detailed analysis of the system’s dynamic reliability properties such as the lifetime of the system, the time it spends in perfect functioning, as well as the total time it spends in partially working states are discussed.
Building languages: Estonian–English two-year-old bilingual’s reliance on patterns in code-mixed utterances
Authors: Baird Piret 
Published: February 2024

Abstract
This paper examines patterns in an Estonian–English bilingual child’s spontaneous speech, employing a computational application of the traceback method, which is used in usage-based linguistics. Forty-five hours of data were analyzed to check what proportion of patterns from code-mixed utterances are attested in the child’s monolingual data and in her input. Pattern overlap between the child’s and the caregivers’ speech was also examined. Results show that about one-third of code-mixed utterances can be traced back to the child’s input and one-third also to her own monolingual data. A little over half of the child’s utterances are either chunks or frame-and-slot patterns from the caregivers’ speech. These results make it evident that the traceback method can also be applied to language pairs that are genealogically more distant, though limitations exist.
Rights and Wrongs in Talk of Mind-Reading Technology
Authors: Rainey Stephen 
Published: February 2024

AbstractThis article examines the idea of mind-reading technology by focusing on an interesting case of applying a large language model (LLM) to brain data. On the face of it, experimental results appear to show that it is possible to reconstruct mental contents directly from brain data by processing via a chatGPT-like LLM. However, the author argues that this apparent conclusion is not warranted. Through examining how LLMs work, it is shown that they are importantly different from natural language. The former operates on the basis of nonrational data transformations based on a large textual corpus. The latter has a rational dimension, being based on reasons. Using this as a basis, it is argued that brain data does not directly reveal mental content, but can be processed to ground predictions indirectly about mental content. The author concludes that this is impressive but different in principle from technology-mediated mind reading. The applications of LLM-based brain data processing are nevertheless promising for speech rehabilitation or novel communication methods.
Transient and Steady‐State Friction in Non‐Isobaric Conditions
Authors: Barbot Sylvain 
Published: February 2024

AbstractThe frictional properties of faults control the initiation and propagation of earthquakes and the associated hazards. Although the ambient temperature and instantaneous slip velocity controls on friction in isobaric conditions are increasingly well understood, the role of normal stress on steady‐state and transient frictional behaviors remains elusive. The friction coefficient of rocks exhibits a strong dependence on normal stress at typical crustal depths. Furthermore, rapid changes in normal stress cause a direct effect on friction followed by an evolutionary response. Here, we derive a constitutive friction law that consistently explains the yield strength of rocks from atmospheric pressure to gigapascals while capturing the transient behavior following perturbations in normal stress. The model explains the frictional strength of a variety of sedimentary, metamorphic, and igneous rocks and the slip‐dependent response upon normal stress steps of Westerly granite bare contact and synthetic gouges made of quartz and a mixture of quartz and smectite. The nonlinear normal stress dependence of the frictional resistance may originate from the distribution of asperities that control the real area of contact. The direct and transient effects may be important for induced seismicity by hydraulic fracturing or for naturally occurring normal stress perturbations within fault zones in the brittle crust.
Reflections on a Century of Extreme Heat Event‐Related Mortality Reporting in Canada
Authors: Yoon Liv , Richardson Gregory R. A. , Gorman Melissa 
Published: February 2024

AbstractClimate change is causing more frequent and severe extreme heat events (EHEs) in Canada, resulting in significant loss of life. However, patterns across mortality reporting for historical EHEs have not been analyzed. To address this gap, we studied deaths in Canadian EHEs from 1936 to 2021, identifying trends and challenges. Our analysis revealed inconsistencies in mortality data, discrepancies between vulnerable populations identified, difficulties in determining the cause of death, and inconsistent reporting on social vulnerability indicators. We provide some observations that could help inform solutions to address the gaps and challenges, by moving toward more consistent and comprehensive reporting to ensure no population is overlooked. Accurately accounting for affected populations could help better target evidence‐based interventions, and reduce vulnerability to extreme heat.
A Preliminary Study on the Identification and Spatio‐Temporal Characteristics of Martian Atmospheric Eddies
Authors: Li Bo , Qu Shaojie , Ling Zongcheng , Chen Shengbo 
Published: February 2024

AbstractAtmospheric eddies serve as a crucial component of global circulation on Mars. It is of great scientific and engineering significance to study the spatio‐temporal characteristics of atmospheric eddies and eddy sequences. In this paper, based on the Open access to Mars Assimilated Remote Soundings (OpenMARS) dataset, we used an eddy detection and sequence tracking method to extract a total of 4,089 eddies in LS = 109° MY28 to LS = 109° MY29, which comprised 3,385 cyclones and 704 anticyclones. Notably, the northern hemisphere exhibited a markedly higher eddy number compared with the southern hemisphere, and more than 82% of eddies had an equivalent radius greater than 400 km. These eddies mainly gathered in the interior and vicinity of basins, mountains, and broad plains in the northern hemisphere. Martian atmospheric eddies can be classified into two categories: topographic eddies, which are related to the various landforms on Mars and non‐topographic eddies, which do not show obvious terrain dependence. Additionally, our analysis yielded 83 extracted eddy sequences, with nearly 90% of them exhibiting short life cycles of less than 40 Martian days (sols). Eddy sequences mainly arise in the spring and summer seasons of the northern hemisphere. Considering the instrument criterion of minimal atmospheric eddy activity for the Tianwen‐3 mission, Chryse Planitia was identified as the optimal landing area.
Sedimentology and Stratigraphy of the Shenandoah Formation, Western Fan, Jezero Crater, Mars
Authors: Stack K. M. , Ives L. R. W. , Gupta S. , Lamb M. P. , Tebolt M. , Caravaca G. , Grotzinger J. P. , Russell P. , Shuster D. L. , Williams A. J. , Amundsen H. , Alwmark S. , Annex A. M. , Barnes R. , Bell J. , Beyssac O. , Bosak T. , Crumpler L. S. , Dehouck E. , Gwizd S. J. , Hickman‐Lewis K. , Horgan B. H. N. , Hurowitz J. , Kalucha H. , Kanine O. , Lesh C. , Maki J. , Mangold N. , Randazzo N. , Seeger C. , Williams R. M. E. , Brown A. , Cardarelli E. , Dypvik H. , Flannery D. , Frydenvang J. , Hamran S.‐E. , Núñez J. I. , Paige D. , Simon J. I. , Tice M. , Tate C. , Wiens R. C. 
Published: February 2024

AbstractSedimentary fans are key targets of exploration on Mars because they record the history of surface aqueous activity and habitability. The sedimentary fan extending from the Neretva Vallis breach of Jezero crater's western rim is one of the Mars 2020 Perseverance rover's main exploration targets. Perseverance spent ∼250 sols exploring and collecting seven rock cores from the lower ∼25 m of sedimentary rock exposed within the fan's eastern scarp, a sequence informally named the “Shenandoah” formation. This study describes the sedimentology and stratigraphy of the Shenandoah formation at two areas, “Cape Nukshak” and “Hawksbill Gap,” including a characterization, interpretation, and depositional framework for the facies that comprise it. The five main facies of the Shenandoah formation include: laminated mudstone, laminated sandstone, low‐angle cross stratified sandstone, thin‐bedded granule sandstone, and thick‐bedded granule‐pebble sandstone and conglomerate. These facies are organized into three facies associations (FA): FA1, comprised of laminated and soft sediment‐deformed sandstone interbedded with broad, unconfined coarser‐grained granule and pebbly sandstone intervals; FA2, comprised predominantly of laterally extensive, soft‐sediment deformed laminated, sulfate‐bearing mudstone with lenses of low‐angle cross‐stratified and scoured sandstone; and FA3, comprised of dipping planar, thin‐bedded sand‐gravel couplets. The depositional model favored for the Shenandoah formation involves the transition from a sand‐dominated distal alluvial fan setting (FA1) to a stable, widespread saline lake (FA2), followed by the progradation of a river delta system (FA3) into the lake basin. This sequence records the initiation of a relatively long‐lived, habitable lacustrine and deltaic environment within Jezero crater.
Abstinence scoring algorithms for treatment of neonatal opioid withdrawal syndrome (NOWS)
Authors: Maisel Brenton A. , Adeniyi-Jones Susan C. , Selvage Eric , Ng Samuel , Kraft Walter K. , Chervoneva Inna 
Published: February 2024

Abstract
Objective
Chervoneva et al. (2020) developed an abbreviated score (sMNAS-9) derived from full modified Finnegan MOTHER NAS scale (MNAS) for evaluating severity of NOWS. We sought to develop NOWS treatment algorithms for clinical decision rules based on scores utilizing the shorter sMNAS.

Study design
This was a retrospective study of 373 infants with NOWS scored with MNAS and treated with morphine between 2007 and 2016. The infants were randomly split into training/test sets. The training set was used to derive optimized cutoff values for sMNAS-9 scores. The independent set evaluated the sMNAS-9 clinical decision rules based on full MNAS in NOWS morphine and buprenorphine treatment algorithms.

Result
Clinical decision rules based on sMNAS-9 yielded sensitivities of 88% or higher and specificities of 85% or higher for predicting the respective rules based on full MNAS.

Conclusion
The sMNAS-9 scoring instrument is expected to yield similar clinical decisions in treatment of NOWS.
A modular microfluidic platform to study how fluid shear stress alters estrogen receptor phenotype in ER+ breast cancer cells
Authors: Ortega Quesada Braulio Andrés , Cuccia Jonathan , Coates Rachael , Nassar Blake , Littlefield Ethan , Martin Elizabeth C. , Melvin Adam T. 
Published: February 2024

AbstractMetastatic breast cancer leads to poor prognoses and worse outcomes in patients due to its invasive behavior and poor response to therapy. It is still unclear what biophysical and biochemical factors drive this more aggressive phenotype in metastatic cancer; however recent studies have suggested that exposure to fluid shear stress in the vasculature could cause this. In this study a modular microfluidic platform capable of mimicking the magnitude of fluid shear stress (FSS) found in human vasculature was designed and fabricated. This device provides a platform to evaluate the effects of FSS on MCF-7 cell line, an estrogen receptor positive (ER+) breast cancer cell line, during circulation in the vessels. Elucidation of the effects of FSS on MCF-7 cells was carried out utilizing two approaches: single cell analysis and bulk analysis. For single cell analysis, cells were trapped in a microarray after exiting the serpentine channel and followed by immunostaining on the device (on-chip). Bulk analysis was performed after cells were collected in a microtube at the outlet of the microfluidic serpentine channel for western blotting (off-chip). It was found that cells exposed to an FSS magnitude of 10 dyn/cm2 with a residence time of 60 s enhanced expression of the proliferation marker Ki67 in the MCF-7 cell line at a single cell level. To understand possible mechanisms for enhanced Ki67 expression, on-chip and off-chip analyses were performed for pro-growth and survival pathways ERK, AKT, and JAK/STAT. Results demonstrated that after shearing the cells phosphorylation of p-AKT, p-mTOR, and p-STAT3 were observed. However, there was no change in p-ERK1/2. AKT is a mediator of ER rapid signaling, analysis of phosphorylated ERα was carried out and no significant differences between sheared and non-sheared populations were observed. Taken together these results demonstrate that FSS can increase phosphorylation of proteins associated with a more aggressive phenotype in circulating cancer cells. These findings provide additional information that may help inform why cancer cells located at metastatic sites are usually more aggressive than primary breast cancer cells.
Tropomyosin1 isoforms underlie epithelial to mesenchymal plasticity, metastatic dissemination, and resistance to chemotherapy in high-grade serous ovarian cancer
Authors: Xu Tong , Verhagen Mathijs P. , Teeuwssen Miriam , Sun Wenjie , Joosten Rosalie , Sacchetti Andrea , Ewing-Graham Patricia C. , Jansen Maurice P. H. M. , Boere Ingrid A. , Bryce Nicole S. , Zeng Jun , Treutlein Herbert R. , Hook Jeff , Hardeman Edna C. , Gunning Peter W. , Fodde Riccardo 
Published: February 2024

AbstractPhenotypic plasticity, defined as the ability of individual cells with stable genotypes to exert different phenotypes upon exposure to specific environmental cues, represent the quintessential hallmark of the cancer cell en route from the primary lesion to distant organ sites where metastatic colonization will occur. Phenotypic plasticity is driven by a broad spectrum of epigenetic mechanisms that allow for the reversibility of epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions (EMT/MET). By taking advantage of the co-existence of epithelial and quasi-mesenchymal cells within immortalized cancer cell lines, we have analyzed the role of EMT-related gene isoforms in the regulation of epithelial mesenchymal plasticity (EMP) in high grade serous ovarian cancer. When compared with colon cancer, a distinct spectrum of downstream targets characterizes quasi-mesenchymal ovarian cancer cells, likely to reflect the different modalities of metastasis formation between these two types of malignancy, i.e. hematogenous in colon and transcoelomic in ovarian cancer. Moreover, upstream RNA-binding proteins differentially expressed between epithelial and quasi-mesenchymal subpopulations of ovarian cancer cells were identified that underlie differential regulation of EMT-related isoforms. In particular, the up- and down-regulation of RBM24 and ESRP1, respectively, represent a main regulator of EMT in ovarian cancer cells. To validate the functional and clinical relevance of our approach, we selected and functionally analyzed the Tropomyosin 1 gene (TPM1), encoding for a protein that specifies the functional characteristics of individual actin filaments in contractile cells, among the ovarian-specific downstream AS targets. The low-molecular weight Tpm1.8/9 isoforms are specifically expressed in patient-derived ascites and promote invasion through activation of EMT and Wnt signaling, together with a broad spectrum of inflammation-related pathways. Moreover, Tpm1.8/9 expression confers resistance to taxane- and platinum-based chemotherapy. Small molecule inhibitors that target the Tpm1 isoforms support targeting Tpm1.8/9 as therapeutic targets for the development of future tailor-made clinical interventions.