bluuebunny/crossref_metadata_2025_split huggingface dataset:
Financial costs to the U.S. Army for suicides by newly enlisted Soldiers
Authors: Schaughency Katherine C. L. , Watkins Eren Youmans , Barnes Stephen , Smith Jacob D. , Forrest Lanna J. , Christopher Phyon K. , Anke Kirsten M. , Sikka Rachana , Pecko Joseph A. , Cox Kenneth L. 
Published: June 2021

AbstractObjectiveTo estimate the financial burden to the U.S. Army of suicide by enlisted Soldiers during their first year of service.MethodsThis analysis included new Army enlisted Soldiers who started initial entry training from October 2012 through September 2016 and subsequently died by suicide within their first year of service. Outpatient and inpatient direct medical, direct nonmedical, recruiting, and training costs to the Army were calculated.ResultsDuring the 48‐month observational study period, 29 Soldiers died by suicide within their respective first year of service. The described financial costs accrued by the Army as a result of these deaths were $152,271—with an average of $6,091 per healthcare utilizer. Recruiting and training costs were $1,115,860 for all suicide cases.ConclusionAverage direct cost per healthcare utilizer increased during a Soldier's first year of service. This may be associated with the transition through different phases of training and to the first operational duty station.Public Health ImplicationsResults obtained through this cost‐of‐illness analysis may serve as baseline metrics to inform future cost‐effectiveness studies.
Oops! I Did it Again: The Psychology of Everyday Action Slips
Authors: Mylopoulos Myrto 
Published: June 2021

AbstractWe have all had the experience of everyday mistakes like distractedly pouring orange juice into our cereal bowl rather than the milk or inadvertently continuing on our regular route home rather than stopping at the store as we had planned. These so‐called "action slips" (Reason, 1984a) are characterized as failures to execute one's intention arising in habitual or highly learned action sequences. This paper argues that a proper understanding of slips, and thus action more generally, requires an understanding of the control structure that implements an agent's guiding intentions. Central to this structure are motor representations that are active downstream of intention and attentional processes that ensure that they reliably implement the intentions they serve.
Therapeutic granulocyte infusion for patients with severe neutropaenia and neutrophilic dysfunction: New Zealand experience
Authors: Chung Shanee , Armstrong‐Scott Oliver , Charlewood Richard 
Published: June 2021

AbstractBackground and ObjectivesStudies have shown granulocyte transfusions (GTXs) may be beneficial in neutropaenic patients with severe systemic infections. New Zealand Blood Service has a policy for provision of granulocytes to New Zealand's District Health Boards. We set out to explore utilization of therapeutic granulocyte infusions in New Zealand.Materials and MethodsPatients who received GTXs in the 16‐year period between 2000 and 2016 were identified by the New Zealand electronic blood management system, eProgesa. Information pertaining to recipient demographics, disease‐related factors, methods of granulocyte collection and clinical outcomes was obtained by the review of electronic transfusion and clinical records.ResultsForty‐five septic patients received granulocyte support for a total of 263 days. The median age of the recipients was 16 (range 0–74) years. Seventy‐nine percent of the recipients had an underlying haematological malignancy with 50% having acute leukaemia. The median neutrophil count on the last day of GTX was 0.02 × 109/L (range 0–16.32). Sixty‐three percent (27/43 patients with available data) had persisting severe neutropaenia when the GTXs were stopped. The median duration of support was 3 (range 1–32) days. Forty‐six percent of granulocyte collections were performed via apheresis. Of the 44 patients, for whom survival outcome was available, 18 (41%) survived the acute illness.ConclusionGTXs were infrequently used, most commonly in the setting of an underlying haematological malignancy. This may be explained by the current weak evidence base supporting this therapeutic modality. Procuring a sufficiently large dose of granulocytes for infusion remains an issue for adult recipients.
Leptin attenuates hypoxia‐induced apoptosis in human periodontal ligament cells via the reactive oxygen species–hypoxia‐inducible factor‐1α pathway
Authors: Gao Jing , Zhu Junfei , Zhao Yuwei , Gan Xueqi , Yu Haiyang 
Published: June 2021

New Findings

What is the central question of this study?
Does leptin have an effect on hypoxia‐induced apoptosis in human periodontal ligament cells (hPDLCs), and what is the potential underlying mechanism?

What is the main finding and its importance?
Hypoxia induces cell apoptosis and leptin expression in hPDLCs through the induction of hypoxia‐inducible factor‐1α and accumulation of reactive oxygen species (ROS). Leptin shows feedback inhibition on hypoxia‐induced ROS‐mediated apoptosis in hPDLCs, suggesting a new application of leptin for hypoxic damage in periodontal diseases.

AbstractHypoxia‐induced apoptosis of human periodontal ligament cells (hPDLCs) is an important contributor to the progression of various periodontal diseases. Although leptin has been shown to protect connective tissue cells against hypoxia‐induced injury, whether it might do so by attenuating hypoxia‐induced apoptosis in hPDLCs remains unclear. Here, using CoCl2 treatment, we simulated hypoxic conditions in hPDLCs and explored whether apoptosis and reactive oxygen species (ROS) levels were related to hypoxia. After small interfering RNA (siRNA) inhibition of leptin and hypoxia‐inducible factor‐1α (HIF‐1α), the levels of apoptosis, ROS and leptin expression were measured. We showed that in CoCl2‐treated hPDLCs, significantly higher cell apoptosis rates and ROS accumulation were observed. Cobalt chloride also increased leptin and HIF‐1α expression in hPDLCs. Further investigation of the pathway demonstrated that inhibition of ROS attenuated hypoxia‐induced cell apoptosis and leptin expression, whereas siRNA inhibition of leptin aggravated hypoxia‐induced cell apoptosis and ROS accumulation. Hypoxia induces cell apoptosis and leptin expression in hPDLCs through the induction of ROS and HIF‐1α pathways, and leptin shows feedback inhibition on ROS‐mediated apoptosis in hPDLCs. These findings suggest a new application of leptin for hypoxic damage in periodontal diseases.
Inverse Design of Axisymmetric Shapes in Glassy Nematic Bilayers
Authors: Xia Shang , He Linghui 
Published: June 2021

Abstract
Programming desired shapes of stimuli-responsive nematic sheets is a challenging yet crucial problem for morphing applications. Here we propose a strategy for inverse design of axisymmetric shapes via circular bilayers composed of two glassy nematic layers with radially symmetric and orthogonal director fields. In this situation, an explicit link can be established between the director orientation and the bilayer deflection. The result provides a recipe for how to construct a director pattern which, upon stimulation, leads to a prescribed shape of revolution. For illustration, two examples concerning simply supported and loosely clamped bilayer discs are given.
Examination of Mechanical Properties and Photoelastic Properties of Gel Material for Blood Vesssel Mimics
Authors: Yamada Daichi , Hori Simon , Abe Shuhe , Kumeno Yuki , Yamazaki Takahiro , Oka Chiemi , Sakurai Junpei , Hata Seiichi 
Published: June 2021

Abstract
Catheter surgery is a minimally invasive treatment in which visual information is limited to a two-dimensional image generated by an X-ray camera. This results in the possibility that stress applied by the catheter onto a blood vessel wall damages the vessel. Doctors must therefore be skillful at catheter surgery. We proposed a catheter surgery simulator that visualizes the stress applied to the blood vessel wall using photoelasticity. The manufacture of this simulator requires creating blood vessel mimics that reproduce the physical properties of blood vessel tissue using photoelasticity. This study investigated the mechanical and photoelastic properties of gel materials and selected a gel composition suitable for making blood vessel mimics. The mechanical properties of polyvinyl alcohol (PVA) hydrogel changed in the range 70–335 kPa by changing the composition ratio, and double network (DN) gel changed in the range 0.13–1.06 MPa by changing the composition ratio. These gels could be adjusted by changing the material composition to provide Young's moduli similar to that of blood vessels. The photoelastic properties of PVA hydrogel changed in the range 1.38–2.76 × 10−9/Pa by changing the composition ratio, and DN gel changed in the range 0.012–0.029 × 10−9/Pa by changing the composition ratio.
A Computational Method for the Estimation of the Geometrical and Thermophysical Properties of Tumor Using Contact Thermometry
Authors: Sudarsan Nimmi , Arathy K. , Antony Linta , Sudheesh R. S. , Muralidharan M. N. , Satheesan B. , Ansari Seema 
Published: June 2021

Abstract
Contact thermometry is the measurement of surface temperature using sensors in contact with the medium. These surface temperatures can be potential indicators of any abnormality possibly a tumor. This research work aims to present a computation method that makes use of contact thermometry to estimate the geometric center, size, and thermophysical properties of breast tumor. Wearable thermal sensors captured real-time surface temperature readings from discrete point locations. The continuous heat distribution over the domain was formulated using forward heat transfer analysis. The optimization method estimated tumor parameters of the breast, and a three-dimensional thermal model was developed from the estimated parameters. Laboratory experiments on breast phantoms were done to validate the estimation method. Furthermore, real-time temperature readings of human subjects were recorded, and the estimated location and size were then compared with the mammogram results. It was found that the estimated two-dimensional geometric center and the size in diameter of the tumor closely match with the mammogram results. Further, the thermophysical properties estimated using the proposed method had a higher order in subjects having a tumor making it a tool for breast cancer screening.
Statistical analysis of tipping pathways in agent-based models
Authors: Helfmann Luzie , Heitzig Jobst , Koltai Péter , Kurths Jürgen , Schütte Christof 
Published: June 2021

AbstractAgent-based models are a natural choice for modeling complex social systems. In such models simple stochastic interaction rules for a large population of individuals on the microscopic scale can lead to emergent dynamics on the macroscopic scale, for instance a sudden shift of majority opinion or behavior. Here we are introducing a methodology for studying noise-induced tipping between relevant subsets of the agent state space representing characteristic configurations. Due to a large number of interacting individuals, agent-based models are high-dimensional, though usually a lower-dimensional structure of the emerging collective behaviour exists. We therefore apply Diffusion Maps, a non-linear dimension reduction technique, to reveal the intrinsic low-dimensional structure. We characterize the tipping behaviour by means of Transition Path Theory, which helps gaining a statistical understanding of the tipping paths such as their distribution, flux and rate. By systematically studying two agent-based models that exhibit a multitude of tipping pathways and cascading effects, we illustrate the practicability of our approach.
A multipurpose end-station for atomic, molecular and optical sciences and coherent diffractive imaging at ELI beamlines
Authors: Klimešová Eva , Kulyk Olena , Hoque Ziaul , Roos Andreas Hult , Khakurel Krishna P. , Rebarz Mateusz , Jurkovičová Lucie , Albrecht Martin , Finke Ondřej , Lera Roberto , Hort Ondřej , Mai Dong-Du , Nejdl Jaroslav , Sokol Martin , Fink Rasmus Burlund , Ben Ltaief Ltaief , Westphal Daniel , Wolf Adam , Laštovička Tomáš , Frassetto Fabio , Poletto Luca , Andreasson Jakob , Krikunova Maria 
Published: June 2021

AbstractWe report on the status of a users’ end-station, MAC: a Multipurpose station for Atomic, molecular and optical sciences and Coherent diffractive imaging, designed for studies of structure and dynamics of matter in the femtosecond time-domain. MAC is located in the E1 experimental hall on the high harmonic generation (HHG) beamline of the ELI Beamlines facility. The extreme ultraviolet beam from the HHG beamline can be used at the MAC end-station together with a synchronized pump beam (which will cover the NIR/Vis/UV or THz range) for time-resolved experiments on different samples. Sample delivery systems at the MAC end-station include a molecular beam, a source for pure or doped clusters, ultrathin cylindrical or flat liquid jets, and focused beams of substrate-free nanoparticles produced by an electrospray or a gas dynamic virtual nozzle combined with an aerodynamic lens stack. We further present the available detectors: electron/ion time-of-flight and velocity map imaging spectrometers and an X-ray camera, and discuss future upgrades: a magnetic bottle electron spectrometer, production of doped nanodroplets and the planned developments of beam capabilities at the MAC end-station.
Chiller
Authors: Zamanian Erfan , Shun Julian , Binnig Carsten , Kraska Tim 
Published: June 2021

Distributed transactions on high-overhead TCP/IP-based networks were conventionally considered to be prohibitively expensive. In fact, the primary goal of existing partitioning schemes is to minimize the number of cross-partition transactions. However, with the new generation of fast RDMAenabled networks, this assumption is no longer valid.
In this paper, we first make the case that the new bottleneck which hinders truly scalable transaction processing in modern RDMA-enabled databases is data contention, and that optimizing for data contention leads to different partitioning layouts than optimizing for the number of distributed transactions. We then present Chiller, a new approach to data partitioning and transaction execution, which aims to minimize data contention for both local and distributed transactions.
Usefulness of Measuring Thiopurine Metabolites in Children with Inflammatory Bowel Disease and Autoimmunological Hepatitis, Treated with Azathioprine
Authors: Bąk-Drabik Katarzyna , Adamczyk Piotr , Duda-Wrońska Justyna , Dąbrowska-Piechota Dominika , Jarzumbek Anna , Kwiecień Jarosław 
Published: June 2021

Introduction. Thiopurines, such as azathioprine (AZA) and 6-mercaptopurine (6-MP), are immunomodulatory agents, used for the maintenance of remission in children with inflammatory bowel disease (IBD)—Crohn’s disease (CD) and ulcerative colitis (UC), as well as with autoimmunological hepatitis (AIH). Measurements of thiopurine metabolites may allow identifying patients at risk for toxicity and nonadherence. It can also provide an explanation for the ineffectiveness of the treatment, observed in some patients. Patients and Methods. A retrospective analysis was carried out of sixty-eight patients (thirty-six patients with CD, eighteen with UC, and fourteen with AIH), treated with AZA. Thiopurine metabolites, 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP), were assayed by high-performance liquid chromatography (HPLC), and the AZA dose was adjusted when 6-TGN concentration was known. Result. Only twenty-five (41%) children had therapeutic 6-TGN concentrations, ten (16%) subjects had suboptimal 6-TGN concentrations, and twenty-six subjects (43%) had 6-TGN concentrations above the recommended therapeutic range. 6-MMP was not above the therapeutic range in any case. Seven subjects revealed undetectable 6-TGN and 6-MMP levels, indicating nonadherence. The mean AZA dose after the 6-TGN concentration-related adjustment did not differ, in comparison to the initial dose, either in IBD or AIH groups. The mean AZA dose was lower in AIH than in IBD. The subjects with an optimal 6-TGN level presented with a higher ratio of remission (88%) than the under- or overdosed patients (60% and 69%), respectively (

Chi
−
square

test
=
3.87

,

p
<
0.05

). Conclusion. Timely measurements of thiopurine metabolites can be a useful tool to identify nonadherent patients before a decision is taken to switch to another drug. We may also spot the patients who receive either too low or too high doses, compensating dose deviations in an appropriate way. The patients with optimal 6-TGN levels presented a higher percentage of remission than the under- or overdosed patients. In most patients, both initial and adjusted AZA doses, lower than suggested in guidelines, appeared to be sufficient to maintain remission.
E2A Modulates Stemness, Metastasis, and Therapeutic Resistance of Breast Cancer
Authors: López-Menéndez Celia , Vázquez-Naharro Alberto , Santos Vanesa , Dubus Pierre , Santamaría Patricia G. , Martínez-Ramírez Ángel , Portillo Francisco , Moreno-Bueno Gema , Faraldo Marisa M. , Cano Amparo 
Published: June 2021

Abstract

Cancer stem cells (CSC) are considered responsible for tumor initiation, therapeutic resistance, and metastasis. A comprehensive knowledge of the mechanisms governing the acquisition and maintenance of cancer stemness is crucial for the development of new therapeutic approaches in oncology. E2A basic helix–loop–helix (bHLH) transcription factors are associated with epithelial–mesenchymal transition (EMT) and tumor progression, but knowledge of their functional contributions to cancer biology is still limited. Using a combination of in vivo and in vitro analyses in a novel PyMT-E2A conditional knockout mouse model and derived primary tumor cell lines, we report here an essential role of E2A in stemness, metastasis, and therapeutic resistance in breast cancer. Targeted deletion of E2A in the mammary gland impaired tumor-initiating ability and dedifferentiation potential and severely compromised metastatic competence of PyMT-driven mammary tumors. Mechanistic studies in PyMT-derived cell lines indicated that E2A actions are mediated by the upregulation of Snai1 transcription. Importantly, high E2A and SNAIL1 expression occurred in aggressive human basal-like breast carcinomas, highlighting the relevance of the E2A–Snail1 axis in metastatic breast cancer. In addition, E2A factors contributed to the maintenance of genomic integrity and resistance to PARP inhibitors in PyMT and human triple-negative breast cancer cells. Collectively, these results support the potential for E2A transcription factors as novel targets worthy of translational consideration in breast cancer.

Significance:
These findings identify key functions of E2A factors in breast cancer cell stemness, metastasis, and drug resistance, supporting a therapeutic vulnerability to targeting E2A proteins in breast cancer.
ENO1 Promotes Lung Cancer Metastasis via HGFR and WNT Signaling–Driven Epithelial-to-Mesenchymal Transition
Authors: Li Hsin-Jung , Ke Feng-Yi , Lin Chia-Ching , Lu Mei-Yi , Kuo Yi-Huei , Wang Yi-Ping , Liang Kang-Hao , Lin Shin-Chang , Chang Ya-Hsuan , Chen Hsuan-Yu , Yang Pan-Chyr , Wu Han-Chung 
Published: June 2021

Abstract

ENO1 (α-enolase) expression is significantly correlated with reduced survival and poor prognosis in many cancer types, including lung cancer. However, the function of ENO1 in carcinogenesis remains elusive. In this study, we found that high expression of ENO1 is present in metastatic lung cancer cell lines and malignant tumors and is associated with poor overall survival of patients with lung cancer. Knockdown of ENO1 decreased cancer cell proliferation and invasiveness, whereas overexpression of ENO1 enhanced these processes. Moreover, ENO1 expression promoted tumor growth in orthotopic models and enhanced lung tumor metastasis in tail-vein injection models. These effects were mediated by upregulation of mesenchymal markers N-cadherin and vimentin and the epithelial-to-mesenchymal transition regulator SLUG, along with concurrent downregulation of E-cadherin. Mechanistically, ENO1 interacted with hepatocyte growth factor receptor (HGFR) and activated HGFR and Wnt signaling via increased phosphorylation of HGFR and the Wnt coreceptor LRP5/6. Activation of these signaling axes decreased GSK3β activity via Src–PI3K–AKT signaling and inactivation of the β-catenin destruction complex to ultimately upregulate SLUG and β-catenin. In addition, we generated a chimeric anti-ENO1 mAb (chENO1-22) that can decrease cancer cell proliferation and invasion. chENO1-22 attenuated cancer cell invasion by inhibiting ENO1-mediated GSK3β inactivation to promote SLUG protein ubiquitination and degradation. Moreover, chENO1-22 prevented lung tumor metastasis and prolonged survival in animal models. Taken together, these findings illuminate the molecular mechanisms underlying the function of ENO1 in lung cancer metastasis and support the therapeutic potential of a novel antibody targeting ENO1 for treating lung cancer.

Significance:
This study shows that ENO1 promotes lung cancer metastasis via HGFR and WNT signaling and introduces a novel anti-ENO1 antibody for potential therapeutic use in lung cancer.
CDK6 Is a Therapeutic Target in Myelofibrosis
Authors: Dutta Avik , Nath Dipmoy , Yang Yue , Le Bao T. , Mohi Golam 
Published: June 2021

Abstract

Myelofibrosis (myelofibrosis) is a deadly blood neoplasia with the worst prognosis among myeloproliferative neoplasms (MPN). The JAK2 inhibitors ruxolitinib and fedratinib have been approved for treatment of myelofibrosis, but they do not offer significant improvement of bone marrow fibrosis. CDK6 expression is significantly elevated in MPN/myelofibrosis hematopoietic progenitor cells. In this study, we investigated the efficacy of CDK4/6 inhibitor palbociclib alone or in combination with ruxolitinib in Jak2V617F and MPLW515L murine models of myelofibrosis. Treatment with palbociclib alone significantly reduced leukocytosis and splenomegaly and inhibited bone marrow fibrosis in Jak2V617F and MPLW515L mouse models of myelofibrosis. Combined treatment of palbociclib and ruxolitinib resulted in normalization of peripheral blood leukocyte counts, marked reduction of spleen size, and abrogation of bone marrow fibrosis in murine models of myelofibrosis. Palbociclib treatment also preferentially inhibited Jak2V617F mutant hematopoietic progenitors in mice. Mechanistically, treatment with palbociclib or depletion of CDK6 inhibited Aurora kinase, NF-κB, and TGFβ signaling pathways in Jak2V617F mutant hematopoietic cells and attenuated expression of fibrotic markers in the bone marrow. Overall, these data suggest that palbociclib in combination with ruxolitinib may have therapeutic potential for treatment of myelofibrosis and support the clinical investigation of this drug combination in patients with myelofibrosis.

Significance:
These findings demonstrate that CDK6 inhibitor palbociclib in combination with ruxolitinib ameliorates myelofibrosis, suggesting this drug combination could be an effective therapeutic strategy against this devastating blood disorder.