bluuebunny/crossref_metadata_2025_split huggingface dataset:
Xanthohumol inhibits non‐small cell lung cancer via directly targeting T‐lymphokine‐activated killer cell‐originated protein kinase
Authors: Zhao Shuang , Cui Jinling , Cao Lixing , Han Kai , Ma Xuan , Chen Hui , Yin Shutao , Zhao Chong , Ma Changwei , Hu Hongbo 
Published: March 2023

AbstractXanthohumol is a principal prenylated chalcone isolated from hops. Previous studies have shown that xanthohumol was effective against various types of cancer, but the mechanisms, especially the direct targets for xanthohumol to exert an anticancer effect, remain elusive. Overexpression of T‐lymphokine‐activated killer cell‐originated protein kinase (TOPK) promotes tumorigenesis, invasion and metastasis, implying the likely potential for targeting TOPK in cancer prevention and treatment. In the present study, we found that xanthohumol significantly inhibited the cell proliferation, migration and invasion of non‐small cell lung cancer (NSCLC) in vitro and suppressed tumor growth in vivo, which is well correlated with inactivating TOPK, evidenced by reduced phosphorylation of TOPK and its downstream signaling histone H3 and Akt, and decreased its kinase activity. Moreover, molecular docking and biomolecular interaction analysis showed that xanthohumol was able to directly bind to the TOPK protein, suggesting that TOPK inactivation by xanthohumol is attributed to its ability to directly interact with TOPK. The findings of the present study identified TOPK as a direct target for xanthohumol to exert its anticancer activity, revealing novel insight into the mechanisms underlying the anticancer activity of xanthohumol.
Adopting Dr. Robot: Responses to competitor adoption of innovation
Authors: Sundaresan Shirish , Boysen Andrew , Nerkar Atul 
Published: March 2023

AbstractResearch SummaryHow do an organization's task requirements affect the ways in which it reacts to competitors' strategic investments? This study uses a novel measure of task requirements (Case Mix Index), to test the competitive and spillover effects of prior adoption on a focal organization's timing of adoption, while accounting for the underlying demand‐side drivers of adoption. Results of an empirical study of the adoption of robotic surgery systems by U.S. hospitals validate our measure as a predictor of the timing of adoption. Further, this measure moderates the effect of adoption by competitors, delaying investment in the technology for those hospitals most likely to adopt robotic surgery based on their patient population, while accelerating adoption for those with the lowest demand for the technology.Managerial SummaryWhen a nearby competitor adopts an important innovation, an organization may react by either imitating their strategy in order to stay competitive or deferring the choice to adopt the technology in order to differentiate and focus elsewhere. Which of these paths it decides to follow may be influenced by the type and difficulty of problems it handles for its customers (task requirements). Using the adoption of robotic surgery in the U.S. Hospital industry, we find that organizations that serve more difficult customer needs defer investment in response to a competitor's technology adoption, while those who address less difficult problems on average are likely to respond by accelerating adoption.
Unbinned multivariate observables for global SMEFT analyses from machine learning
Authors: Ambrosio Raquel Gomez , ter Hoeve Jaco , Madigan Maeve , Rojo Juan , Sanz Veronica 
Published: March 2023

Abstract
Theoretical interpretations of particle physics data, such as the determination of the Wilson coefficients of the Standard Model Effective Field Theory (SMEFT), often involve the inference of multiple parameters from a global dataset. Optimizing such interpretations requires the identification of observables that exhibit the highest possible sensitivity to the underlying theory parameters. In this work we develop a flexible open source frame-work, ML4EFT, enabling the integration of unbinned multivariate observables into global SMEFT fits. As compared to traditional measurements, such observables enhance the sensitivity to the theory parameters by preventing the information loss incurred when binning in a subset of final-state kinematic variables. Our strategy combines machine learning regression and classification techniques to parameterize high-dimensional likelihood ratios, using the Monte Carlo replica method to estimate and propagate methodological uncertainties. As a proof of concept we construct unbinned multivariate observables for top-quark pair and Higgs+Z production at the LHC, demonstrate their impact on the SMEFT parameter space as compared to binned measurements, and study the improved constraints associated to multivariate inputs. Since the number of neural networks to be trained scales quadratically with the number of parameters and can be fully parallelized, the ML4EFT framework is well-suited to construct unbinned multivariate observables which depend on up to tens of EFT coefficients, as required in global fits.
Institutions and economic development: new measurements and evidence
Authors: Acquah Esther , Carbonari Lorenzo , Farcomeni Alessio , Trovato Giovanni 
Published: March 2023

AbstractWe propose a new set of indices to capture the multidimensionality of a country’s institutional setting. Our indices are obtained by employing a dimension reduction approach on the institutional variables provided by the Fraser Institute (2018). We estimate the impact that institutions have on the level and the growth rate of per capita GDP, using a large sample of countries over the period 1980–2015. To identify the causal effect of our institutional indices on a country’s GDP we employ the Generalized Propensity Score method. Institutions matter especially in low- and middle-income countries, and not all institutions are alike for economic development. We also document non-linearities in the causal effects that different institutions have on growth and the presence of threshold effects.
Innovate to lead or innovate to prevail: When do monopolistic rents induce growth?
Authors: Piazza Roberto , Zheng Yu 
Published: March 2023

AbstractThis paper extends the standard Schumpeterian model of creative destruction by allowing the cost of innovation for followers to increase in their technological distance from the leader. This assumption is motivated by the observation that the more technologically advanced the leader is, the harder it is for a follower to leapfrog without incurring extra cost for using leader’s patented knowledge. Under this R &D cost structure, leaders have an incentive to play an “endpoint strategy": they increase their technological advantage, counting on the fact that followers will eventually stop innovating—allowing leadership to prevail. We find that several results in the standard model fail to hold. In addition to the high-growth steady state in which only followers innovate, there now exists a second saddle-path-stable steady state: a low-growth steady state that features both leaders and followers innovating. A policy that increases monopolistic rents or extends parent duration can push the economy toward the low-growth steady state, causing, in some cases, irreversible harm to long-run growth.
Isomonodromic Tau Functions on a Torus as Fredholm Determinants, and Charged Partitions
Authors: Del Monte Fabrizio , Desiraju Harini , Gavrylenko Pavlo 
Published: March 2023

AbstractWe prove that the isomonodromic tau function on a torus with Fuchsian singularities and generic monodromies in $$GL(N,{\mathbb {C}})$$

G
L
(
N
,
C
)

can be written in terms of a Fredholm determinant of Plemelj operators. We further show that the minor expansion of this Fredholm determinant is described by a series labeled by charged partitions. As an example, we show that in the case of $$SL(2,{\mathbb {C}})$$

S
L
(
2
,
C
)

this combinatorial expression takes the form of a dual Nekrasov–Okounkov partition function, or equivalently of a free fermion conformal block on the torus. Based on these results we also propose a definition of the tau function of the Riemann–Hilbert problem on a torus with generic jump on the A-cycle.
Can the Realization of an External Wirsungostomy be an Option for High‐Risk Pancreatic Anastomosis After Pancreaticoduodenectomy?
Authors: Codjia Tatiana , Roussel Edouard , Papet Eloise , Pinson Jean , Monge Matthieu , Tortajada Pauline , Tuech Jean‐Jacques , Schwarz Lilian 
Published: March 2023

AbstractBackgroundClinically relevant postoperative pancreatic fistula (POPF) occurs in 15–20% of patients after pancreaticoduodenectomy (PD) and reintervention in the setting of Grade C POPF remains associated with a mortality rate of up to 25%. In patients at high risk of POPF, PD with external wirsungostomy (EW) could be a safe alternative that avoids pancreatico‐enteric anastomosis while preserving the remnant pancreas.MethodsOf the 155 consecutive patients who underwent PD from November 2015 to December 2020, 10 patients were managed using an EW, all with a fistula risk score (FRS) ≥ 7 and BMI ≥30 kg/m2, and/or major associated abdominal surgery. The pancreatic duct was cannulated with a polyethylene tube to allow good external drainage of the pancreatic fluid. We retrospectively analyzed postoperative complications and endocrine and exocrine insufficiencies.ResultsThe median alternative FRS was 36.9% [22.1–45.2]. There was no postoperative death. The 90‐day overall severe complication (grade  ≥3) rate was 30% (n = 3 patients), no patient required reoperation, and 2 hospital readmissions occurred. 3 patients experienced Grade B POPF (30%), managed using image‐guided drainage for 2 patients. The external pancreatic drain was removed after a median drainage time of 75 days [63–80]. Two patients presented with late symptoms (> 6 months) warranting interventional management (pancreaticojejunostomy and transgastric drainage). Six patients experienced significant weight loss (> 2 kg) 3 months after surgery. One year after surgery, 4 patients still complained of diarrhea and were treated with transit‐delaying drugs. One patient presented new‐onset diabetes one year after surgery, and 1 of the 4 patients with preexisting diabetes experienced worsening disease.ConclusionEW after PD might be a solution to reduce post‐operative mortality following PD in high‐risk patients.
Scaling Surgical Resources: A Capacity Analysis of C‐arm Machines in Haiti Following the 2021 Earthquake
Authors: Franco Helena , Simister Samuel , Njai Abdoulie , Woolley Pierre Marie , Joseph Michelle Nyah 
Published: March 2023

AbstractBackgroundIn 2021, a 7.2 magnitude earthquake struck Haiti resulting in a surge of orthopaedic trauma requiring immediate surgical treatment. Safe and efficient operative management of orthopaedic trauma injuries requires intraoperative fluoroscopy through C‐arm machines. The Haitian Health Network (HHN) received a philanthropic donation of three C‐arm machines and considered an analytical tool may guide efficacious placement of those machines. The study objective was to develop and apply a clinical needs and hospital readiness measuring tool relevant to C‐arm machines, which may guide decision‐makers, such as HHN, in response to an emergency situation with a surge in need for orthopaedic treatment.MethodsAn online survey to assess surgical volume and capacity was created and then completed by a senior surgeon or hospital administrator based at hospitals within the HHN. Multiple‐choice and free‐text answer data were collected and classified into five categories: staff, space, stuff, systems, and surgical capacity. Each hospital received a final score out of 100, calculated by equal weighting of each category.ResultsTen out of twelve hospitals completed the survey. The average weighted score for the staff category was 10.2 (SD 5.12), the space category was 13.1 (SD 4.09), the stuff category was 15.6 (SD 2.56), the systems category was 12.25 (SD 6.50), and the surgical capacity category was 9.5 (SD 6.47). The average final hospital scores ranged from 29.5 to 83.0.ConclusionThis analysis tool provided data as to the clinical demand and capabilities of hospitals within the HHN to receive a C‐arm machine and reaffirmed the critical need for more C‐arms in Haiti. This methodology may be utilised by other health systems to provide data to distribute orthopaedic trauma equipment, which would benefit communities during periods of surge capacity, such as natural disasters.
On Two Coupled Degenerate Parabolic Equations Motivated by Thermodynamics
Authors: Mielke Alexander 
Published: March 2023

AbstractWe discuss a system of two coupled parabolic equations that have degenerate diffusion constants depending on the energy-like variable. The dissipation of the velocity-like variable is fed as a source term into the energy equation leading to conservation of the total energy. The motivation of studying this system comes from Prandtl’s and Kolmogorov’s one- and two-equation models for turbulence, where the energy-like variable is the mean turbulent kinetic energy. Because of the degeneracies, there are solutions with time-dependent support like in the porous medium equation, which is contained in our system as a special case. The motion of the free boundary may be driven by either self-diffusion of the energy-like variable or by dissipation of the velocity-like variable. The crossover of these two phenomena is exemplified for the associated planar traveling fronts. We provide existence of suitably defined weak and very weak solutions. After providing a thermodynamically motivated gradient structure, we also establish convergence into steady state for bounded domains and provide a conjecture on the asymptotically self-similar behavior of the solutions in $$\mathbb {R}^d$$

R

d

for large times.
Esmethadone-HCl (REL-1017): a promising rapid antidepressant
Authors: Fava Maurizio , Stahl Stephen M. , De Martin Sara , Mattarei Andrea , Bettini Ezio , Comai Stefano , Alimonti Andrea , Bifari Francesco , Pani Luca , Folli Franco , Guidetti Clotilde , Furlan Alberto , Sgrignani Jacopo , Locatelli Patrizia , Cavalli Andrea , O’Gorman Cedric , Traversa Sergio , Inturrisi Charles E. , Pappagallo Marco , Manfredi Paolo L. 
Published: March 2023

AbstractThis review article presents select recent studies that form the basis for the development of esmethadone into a potential new drug. Esmethadone is a promising member of the pharmacological class of uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists that have shown efficacy for major depressive disorder (MDD) and other diseases and disorders, such as Alzheimer’s dementia and pseudobulbar affect. The other drugs in the novel class of NMDAR antagonists with therapeutic uses that are discussed for comparative purposes in this review are esketamine, ketamine, dextromethorphan, and memantine. We present in silico, in vitro, in vivo, and clinical data for esmethadone and other uncompetitive NMDAR antagonists that may advance our understanding of the role of these receptors in neural plasticity in health and disease. The efficacy of NMDAR antagonists as rapid antidepressants may advance our understanding of the neurobiology of MDD and other neuropsychiatric diseases and disorders.
Diagnosis and treatment of MPN in real life: exploratory and retrospective chart review including 960 MPN patients diagnosed with ET or MF in Germany
Authors: Schmidt Andreas , Bernhardt Christiane , Bürkle Dieter , Fries Stefan , Hannig Carla V. , Jentsch-Ullrich Kathleen , Josting Andreas , Kreher Stephan , Reiser Marcel , Steinmetz Hans Tilman , Tesch Hans , Terner Stephanie , Schulte Alexander , Crodel Carl C. , Palandri Francesca , Heidel Florian H. 
Published: March 2023

Abstract
Purpose
The WHO 2016 re-classification of myeloproliferative neoplasms resulted in a separation of essential thrombocythemia (ET) from the pre-fibrotic and fibrotic (overt) phases of primary myelofibrosis (MF). This study reports on a chart review conducted to evaluate the real life approach regarding clinical characteristics, diagnostic assessment, risk stratification and treatment decisions for MPN patients classified as ET or MF after implementation of the WHO 2016 classification.

Methods
In this retrospective chart review, 31 office-based hematologists/oncologists and primary care centers in Germany participated between April 2021 and May 2022. Physicians reported available data obtained from patient charts via paper–pencil based survey (secondary use of data). Patient features were evaluated using descriptive analysis, also including diagnostic assessment, therapeutic strategies and risk stratification.

Results
Data of 960 MPN patients diagnosed with essential thrombocythemia (ET) (n = 495) or myelofibrosis (MF) (n = 465) after implementation of the revised 2016 WHO classification of myeloid neoplasms was collected from the patient charts. While they met at least one minor WHO-criteria for primary myelofibrosis, 39.8% of those diagnosed with ET did not have histological BM testing at diagnosis. 63.4% of patients who were classified as having MF, however, did not obtain an early prognostic risk assessment. More than 50% of MF patients showed characteristics consistent with the pre-fibrotic phase, which was emphasized by the frequent use of cytoreductive therapy. Hydroxyurea was the most frequently used cytoreductive medication in 84.7% of ET and 53.1% of MF patients. While both ET and MF cohorts showed cardiovascular risk factors in more than 2/3 of the cases, the use of platelet inhibitors or anticoagulants varied between 56.8% in ET and 38.1% in MF patients.

Conclusions
Improved histopathologic diagnostics, dynamic risk stratification including genetic risk factors for cases of suspected ET and MF are recommended for precise risk assessment and therapeutic stratification according to WHO criteria.
Comparison of outcomes of proximal versus distal and combined splenic artery embolization in the management of blunt splenic injury: a report of 202 cases from a single trauma center
Authors: Lin Being-Chuan , Wu Cheng-Hsien , Wong Yon-Cheong , Chen Huan-Wu , Fu Chen-Ju , Huang Chen-Chih , Wu Chen-Te , Ku Yi-Kang , Chen Chien-Cheng , Sheng Ting-Wen , Chang Chun-Bi 
Published: March 2023

Abstract
Background
To compare the outcomes of blunt splenic injuries (BSI) managed with proximal (P) versus distal (D) versus combined (C) splenic artery embolization (SAE).

Methods
This retrospective study included patients with BSI who demonstrated vascular injuries on angiograms and were managed with SAE between 2001 and 2015. The success rate and major complications (Clavien–Dindo classification ≥ III) were compared between the P, D, and C embolizations.

Results
In total, 202 patients were enrolled (P, n = 64, 31.7%; D, n = 84, 41.6%; C, n = 54, 26.7%). The median injury severity score was 25. The median times from injury to SAE were 8.3, 7.0, and 6.6 h for the P, D, and C embolization, respectively. The overall haemostasis success rates were 92.6%, 93.8%, 88.1%, and 98.1% in the P, D, and C embolizations, respectively, with no significant difference (p = 0.079). Additionally, the outcomes were not significantly different between the different types of vascular injuries on angiograms or the materials used in the location of embolization. Splenic abscess occurred in six patients (P, n = 0; D, n = 5; C, n = 1), although it occurred more commonly in those who underwent D embolization with no significant difference (p = 0.092).

Conclusions
The success rate and major complications of SAE were not significantly different regardless of the location of embolization. The different types of vascular injuries on angiograms and agents used in different embolization locations also did not affect the outcomes.

Graphical abstract
A deep learning-based histopathology classifier for Focal Cortical Dysplasia
Authors: Vorndran Jörg , Neuner Christoph , Coras Roland , Hoffmann Lucas , Geffers Simon , Honke Jonas , Herms Jochen , Roeber Sigrun , Hamer Hajo , Brandner Sebastian , Hartlieb Till , Pieper Tom , Kudernatsch Manfred , Bien Christian G. , Kalbhenn Thilo , Simon Matthias , Adle-Biassette Homa , Cienfuegos Jesús , Di Giacomo Roberta , Garbelli Rita , Miyata Hajime , Mühlebner Angelika , Raicevic Savo , Rauramaa Tuomas , Rogerio Fabio , Blümcke Ingmar , Jabari Samir 
Published: March 2023

AbstractA light microscopy-based histopathology diagnosis of human brain specimens obtained from epilepsy surgery remains the gold standard to confirm the underlying cause of a patient’s focal epilepsy and further inform postsurgical patient management. The differential diagnosis of neocortical specimens in the realm of epilepsy surgery remains, however, challenging. Herein, we developed an open access, deep learning-based classifier to histopathologically assess whole slide microscopy images (WSI) and to automatically recognize various subtypes of Focal Cortical Dysplasia (FCD), according to the ILAE consensus classification update of 2022. We trained a convolutional neuronal network (CNN) with fully digitalized WSI of hematoxylin–eosin stainings obtained from 125 patients covering the spectrum of mild malformation of cortical development (mMCD), mMCD with oligodendroglial hyperplasia in epilepsy (MOGHE), FCD ILAE Type 1a, 2a and 2b using 414 formalin-fixed and paraffin-embedded archival tissue blocks. An additional series of 198 postmortem tissue blocks from 59 patients without neurological disorders served as control to train the CNN for homotypic frontal, temporal and occipital areas and heterotypic Brodmann areas 4 and 17, entorhinal cortex and dentate gyrus. Special stains and immunohistochemical reactions were used to comprehensively annotate the region of interest. We then programmed a novel tile extraction pipeline and graphical dashboard to visualize all areas on the WSI recognized by the CNN. Our deep learning-based classifier is able to compute 1000 × 1000 µm large tiles and recognizes 25 anatomical regions and FCD categories with an accuracy of 98.8% (F1 score = 0.82). Microscopic review of regions predicted by the network confirmed these results. This deep learning-based classifier will be made available as online web application to support the differential histopathology diagnosis in neocortical human brain specimens obtained from epilepsy surgery. It will also serve as blueprint to build a digital histopathology slide suite addressing all major brain diseases encountered in patients with surgically amenable focal epilepsy.
Spatial coherence patterns of extreme winter precipitation in the U.S.
Authors: Banerjee Abhirup , Kemter Matthias , Goswami Bedartha , Merz Bruno , Kurths Jürgen , Marwan Norbert 
Published: March 2023

AbstractExtreme precipitation events have a significant impact on life and property. The U.S. experiences huge economic losses due to severe floods caused by extreme precipitation. With the complex terrain of the region, it becomes increasingly important to understand the spatial variability of extreme precipitation to conduct a proper risk assessment of natural hazards such as floods. In this work, we use a complex network-based approach to identify distinct regions exhibiting spatially coherent precipitation patterns due to various underlying climate mechanisms. To quantify interactions between event series of different locations, we use a nonlinear similarity measure, called the edit-distance method, which considers not only the occurrence of the extreme events but also their intensity, while measuring similarity between two event series. Using network measures, namely, degree and betweenness centrality, we are able to identify the specific regions affected by the landfall of atmospheric rivers in addition to those where the extreme precipitation due to storm track activity is modulated by different mountain ranges such as the Rockies and the Appalachians. Our approach provides a comprehensive picture of the spatial patterns of extreme winter precipitation in the U.S. due to various climate processes despite its vast, complex topography.