bluuebunny/crossref_metadata_2025_split huggingface dataset:
The beneficial effects of commensal E. coli for colon epithelial cell recovery are related with Formyl peptide receptor 2 (Fpr2) in epithelial cells
Authors: Chen Keqiang , McCulloch John , Das Neves Rodrigo , Rodrigues Gisele , Hsieh Wang-Ting , Gong Wanghua , Yoshimura Teizo , Huang Jiaqiang , O’hUigin Colm , Difilippantonio Simone , McCollum Matthew , Jones Georgette , Durum Scott K. , Trinchieri Giorgio , Wang Ji Ming 
Published: June 2023

Abstract
Background
Formyl peptide receptor 2 (Fpr2) plays a crucial role in colon homeostasis and microbiota balance. Commensal E. coli is known to promote the regeneration of damaged colon epithelial cells. The aim of the study was to investigate the connection between E. coli and Fpr2 in the recovery of colon epithelial cells.

Results
The deficiency of Fpr2 was associated with impaired integrity of the colon mucosa and an imbalance of microbiota, characterized by the enrichment of Proteobacteria in the colon. Two serotypes of E. coli, O22:H8 and O91:H21, were identified in the mouse colon through complete genome sequencing. E. coli O22:H8 was found to be prevalent in the gut of mice and exhibited lower virulence compared to O91:H21. Germ-free (GF) mice that were pre-orally inoculated with E. coli O22:H8 showed reduced susceptibility to chemically induced colitis, increased proliferation of epithelial cells, and improved mouse survival. Following infection with E. coli O22:H8, the expression of Fpr2 in colon epithelial cells was upregulated, and the products derived from E. coli O22:H8 induced migration and proliferation of colon epithelial cells through Fpr2. Fpr2 deficiency increased susceptibility to chemically induced colitis, delayed the repair of damaged colon epithelial cells, and heightened inflammatory responses. Additionally, the population of E. coli was observed to increase in the colons of Fpr2−/− mice with colitis.

Conclusion
Commensal E. coli O22:H8 stimulated the upregulation of Fpr2 expression in colon epithelial cells, and the products from E. coli induced migration and proliferation of colon epithelial cells through Fpr2. Fpr2 deficiency led to an increased E. coli population in the colon and delayed recovery of damaged colon epithelial cells in mice with colitis. Therefore, Fpr2 is essential for the effects of commensal E. coli on colon epithelial cell recovery.
Economics of Yak herding in the Kanchenjunga landscape of the Eastern Himalayas
Authors: Rai Rajesh K. , Joshi Srijana , Dorji Tashi , Pant Basant 
Published: June 2023

AbstractYak herding is one of the oldest market-based traditions, which is part of an integrated social-ecological system. But, it is at risk of extinction as yak herders are gradually shifting towards alternative occupations. The discontinuation of herding may have several implications such as loss of culture and degradation of the rangeland ecosystem. Though yak herding is not limited to the financial aspect of herding, this is considered a main cause of the discontinuation. Therefore, it is important to understand the economics of yak herding. A benefit–cost analysis of yak herding was carried out based on the interviews with 60 yak herders in the Kanchenjunga landscape, Nepal. The results indicate that yak herding is not financially attractive. High mortality of calves and adults is threatening this occupation, and degrading rangelands are increasing the costs. Yak herding generates substantial amount of social and ecological benefits in terms of preserving culture, maintaining rangeland ecosystems and curbing illegal activities. If these benefits are included, then the benefit–cost ratio and internal rate of return would be 1.32 and 10.44 respectively. Since yak herding generates low direct profits and requires herders to stay in remote areas, there is a high risk of discontinuation of this profession by successive generations of youth. This study suggests to improve rangeland management through prescribed burning and provisioning of health services, particularly in summer pastures and incentivize yak herders for generating positive externalities.
Treatment of critically ill patients with cefiderocol for infections caused by multidrug-resistant pathogens: review of the evidence
Authors: Viale Pierluigi , Sandrock Christian E. , Ramirez Paula , Rossolini Gian Maria , Lodise Thomas P. 
Published: June 2023

AbstractAppropriate antibiotic treatment for critically ill patients with serious Gram-negative infections in the intensive care unit is crucial to minimize morbidity and mortality. Several new antibiotics have shown in vitro activity against carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat resistant Pseudomonas aeruginosa. Cefiderocol is the first approved siderophore beta-lactam antibiotic with potent activity against multidrug-resistant, carbapenem-resistant, difficult-to-treat or extensively drug-resistant Gram-negative pathogens, which have limited treatment options. The spectrum of activity of cefiderocol includes drug-resistant strains of Acinetobacter baumannii, P. aeruginosa, Stenotrophomonas maltophilia, Achromobacter spp. and Burkholderia spp. and CRE that produce serine- and/or metallo-carbapenemases. Phase 1 studies established that cefiderocol achieves adequate concentration in the epithelial lining fluid in the lung and requires dosing adjustment for renal function, including patients with augmented renal clearance and continuous renal-replacement therapy (CRRT); no clinically significant drug–drug interactions are expected. The non-inferiority of cefiderocol versus high-dose, extended-infusion meropenem in all-cause mortality (ACM) rates at day 14 was demonstrated in the randomized, double-blind APEKS–NP Phase 3 clinical study in patients with nosocomial pneumonia caused by suspected or confirmed Gram-negative bacteria. Furthermore, the efficacy of cefiderocol was investigated in the randomized, open-label, pathogen-focused, descriptive CREDIBLE–CR Phase 3 clinical study in its target patient population with serious carbapenem-resistant Gram-negative infections, including hospitalized patients with nosocomial pneumonia, bloodstream infection/sepsis, or complicated urinary tract infections. However, a numerically greater ACM rate with cefiderocol compared with BAT led to the inclusion of a warning in US and European prescribing information. Cefiderocol susceptibility results obtained with commercial tests should be carefully evaluated due to current issues regarding their accuracy and reliability. Since its approval, real-world evidence in patients with multidrug-resistant and carbapenem-resistant Gram-negative bacterial infections suggests that cefiderocol can be efficacious in certain critically ill patient groups, such as those requiring mechanical ventilation for COVID-19 pneumonia with subsequently acquired Gram-negative bacterial superinfection, and patients with CRRT and/or extracorporeal membrane oxygenation. In this article, we review the microbiological spectrum, pharmacokinetics/pharmacodynamics, efficacy and safety profiles and real-world evidence for cefiderocol, and look at future considerations for its role in the treatment of critically ill patients with challenging Gram-negative bacterial infections.
Efficacy and safety of proxalutamide (GT0918) in severe or critically ill patients with COVID-19: study protocol for a prospective, open-label, single-arm, single-center exploratory trial
Authors: Yang Dawei , Ju Minjie , Wang Hao , Jia Yichen , Wang Xiaodan , Fang Hao , Fan Jia 
Published: June 2023

Abstract
Background
The rapid worldwide spread of COVID-19 has caused a global health challenge with high mortality of severe or critically ill patients with COVID-19. To date, there is no specific efficient therapeutics for severe or critically ill patients with COVID-19. It has been reported that androgen is related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Proxalutamide as an androgen receptor antagonist has shown potential treatment effects on COVID-19 patients. Thus, this trial is designed to investigate the efficacy and safety of proxalutamide in severe or critically ill patients with COVID-19.

Methods
This single-arm, open-label, single-center prospective exploratory trial is planned to recruit 64 severe or critically ill patients with COVID-19 in China. Recruitment started on 16 May 2022 and is foreseen to end on 16 May 2023. Patients will be followed-up until 60 days or death, whichever comes first. The primary outcome is the 30-day all-cause mortality. Secondary endpoints included 60-day all-cause mortality, rate of clinical deterioration within 30 days after administration, time to sustain clinical recovery (determined using an 8-point ordinal scale), mean change in the Acute Physiology and Chronic Health Evaluation II scores, change in oxygenation index, changes in chest CT scan, percentage of patients confirmed negative for SARS-CoV-2 by nasopharyngeal swab, change in Ct values of SARS-CoV-2 and safety. Visits will be performed on days 1 (baseline), 15 or 30, 22, and 60.

Discussion
The trial is the first to investigate the efficacy and safety of proxalutamide in severe or critically ill patients with COVID-19. The findings of this study might lead to the development of better treatment for COVID-19 and provide convincing evidence regarding the efficacy and safety of proxalutamide.

Trial registration
This study was registered on 18 June 2022 at the Chinese Clinical Trial Registry (ChiCTR2200061250).
Strong-motion simulation for the 1944 Tonankai earthquake based on the statistical green’s function method and stochastic representation of complex source process
Authors: Ito Eri , Nakano Kenichi , Sekiguchi Haruko , Nagashima Fumiaki , Kawase Hiroshi 
Published: June 2023

AbstractPrecisely evaluating the source, path, and site terms in a broadband frequency range is indispensable for quantitatively predicting strong motions. We conducted a generalized spectral inversion of strong motion in Japan to delineate both the spectral amplitude and phase characteristics for statistical Green’s functions. To predict ground motion from future megathrust earthquakes, we also need to model a kinematic source with a stochastic representation of the slip and rupture velocities on the fault surface. In this fundamental study, we first reported the basic features of statistical Green’s functions used for summation. We then demonstrated the construction of a kinematic source with distinctive strong-motion-generation areas with spatially random slip and rupture velocity variations. After the summation of statistical Green’s functions following the constructed kinematic source, we found that the peak ground accelerations and peak ground velocities of synthetics for the Mw8.2 1944 Tonankai earthquake are in good agreement with those of the well-established empirical formula in Japan because the medians of the synthetic values are well within the average plus/minus one standard deviation of the formula. Based on the simulation results of conducted parametric studies, we observed relatively small but meaningful effects of random slip distribution, as well as relatively small effects of random rupture velocity perturbation. In conclusion, our implementation of the complex source model and the empirically obtained statistical Green’s function used as an element source can be a viable combination for broadband (0.1 to 20 Hz) strong-motion simulations, realistic in terms of the amplitude and duration, without any hybrid scheme.
Graphical Abstract
Association between D-dimer and long-term mortality in patients with acute severe hypertension visiting the emergency department
Authors: Kim Byung Sik , Shin Jeong-Hun 
Published: June 2023

Abstract
Objective
High levels of d-dimer, a marker of thrombotic events, are associated with poor outcomes in patients with various cardiovascular diseases. However, there has been no research on its prognostic implications in acute severe hypertension. This study investigated the association between d-dimer levels and long-term mortality in patients with severe acute hypertension who visited the emergency department.

Design and method
This observational study included patients with acute severe hypertension who visited the emergency department between 2016 and 2019. Acute severe hypertension was defined as a systolic blood pressure ≥ 180 mmHg or a diastolic blood pressure ≥ 100 mmHg. Among the 10,219 patients, 4,127 who underwent d-dimer assay were analyzed. The patients were categorized into tertiles based on their d-dimer levels at the time of emergency department admission.

Results
Among the 4,127 patients with acute severe hypertension, 3.1% in the first (lowest) tertile, 17.0% in the second tertile, and 43.2% in the third (highest) tertile died within 3 years. After the adjustment for confounding variables, the third tertile of the d-dimer group (hazard ratio, 6.440; 95% confidence interval, 4.628–8.961) and the second tertile of the d-dimer group (hazard ratio, 2.847; 95% confidence interval, 2.037–3.978) had a significantly higher risk of all-cause mortality over 3 years than the first tertile of the d-dimer group.

Conclusions
d-dimer may be a useful marker for identifying the risk of mortality among patients with acute severe hypertension who visit the emergency department.
Extending Technology Acceptance Model to higher-education students’ use of digital academic reading tools on computers
Authors: Lin Yupeng , Yu Zhonggen 
Published: June 2023

AbstractDigital academic reading tools on computers bring multiple benefits to higher-education students. Through structural equation modeling methods, this study contributes to the following findings: (1) Perceived ease of use, perceived usefulness, and lecturers’ positive responses significantly predict students’ positive attitudes toward digital academic reading tools on computers; (2) perceived ease of use, lectures’ positive responses, and expectations of academic achievement are significantly positive predictors of students’ perceived usefulness of these tools; (3) attitudes and expectations of academic achievement significantly predict students’ positive intentions to use these tools; (4) academic experience significantly predicts students’ negative attitudes toward these tools; (5) perceived ease for collaborative learning and self-efficacy are significantly positive predictors of students’ perceived ease of using these tools. Findings in this study may contribute to understanding the external factors influencing students’ acceptance and use of digital academic reading tools on computers with a substantial explanatory power of the proposed model (R2 = 64.70–84.20%), which may benefit researchers, instructors, students, and technology designers.
Guideline “Motor neuron diseases” of the German Society of Neurology (Deutsche Gesellschaft für Neurologie)
Authors: Petri Susanne , Grehl Torsten , Grosskreutz Julian , Hecht Martin , Hermann Andreas , Jesse Sarah , Lingor Paul , Löscher Wolfgang , Maier André , Schoser Benedikt , Weber Marcus , Ludolph Albert C. 
Published: June 2023

Abstract
Introduction
In 2021, the Deutsche Gesellschaft für Neurology published a new guideline on diagnosis and therapy of motor neuron disorders. Motor neuron disorders affect upper motor neurons in the primary motor cortex and/or lower motor neurons in the brain stem and spinal cord. The most frequent motor neuron disease amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease with an average life expectancy of 2–4 years with a yearly incidence of 3.1/100,000 in Central Europe (Rosenbohm et al. in J Neurol 264(4):749–757, 2017. https://doi.org/10.1007/s00415-017-8413-3). It is considered a rare disease mainly due to its low prevalence as a consequence of short disease duration.

Recommendations
These guidelines comprise recommendations regarding differential diagnosis, neuroprotective therapies and multidisciplinary palliative care including management of respiration and nutrition as well as provision of assistive devices and end-of-life situations.

Conclusion
Diagnostic and therapeutic guidelines are necessary due the comparatively high number of cases and the aggressive disease course. Given the low prevalence and the severe impairment of patients, it is often impossible to generate evidence-based data so that ALS guidelines are partially dependent on expert opinion.
Effective Long-term Pediatric Pegvisomant Monotherapy to Final Height in X-linked Acrogigantism
Authors: Burren Christine P , Williams Georgina , Coxson Edward , Korbonits Márta 
Published: June 2023

Abstract
X-linked acrogigantism (X-LAG) is characterized by extreme tall stature from early childhood resulting from duplication of the GPR101 gene, in turn resulting in GH excess. Most cases present with pituitary tumors secreting GH and prolactin. Diffuse pituitary hyperplasia is uncommon and normal prolactin is rare. We present a girl with tall stature from 3 years of age; her height was +4.25 SD score at 5 years, with no signs of syndromic disease. She had significant GH excess, serum IGF-1 4 times the upper limit of normal and normal circulating GHRH, with normal pituitary magnetic resonance imaging over 13 years. No abnormalities were found in either the AIP or MEN1 genes. Treatment with somatostatin analogues and dopamine agonists showed minimal therapeutic benefit, but significant side effects. She tested positive for duplication of GPR101 6 years after the initial diagnosis. She was then initiated on pegvisomant aged 12 years, achieving prompt IGF-1 normalization and growth cessation. Aged 16.5 years, she showed escape from IGF-1 control, and height velocity increased, but this responded well to a dose increase in pegvisomant, with reassuring long-term pediatric safety over 7 years. Her final height is +2.9 SD score. Currently, life-long pegvisomant treatment is planned with genetic counselling regarding future offspring.
Thyrotoxicosis and Impending Thyroid Storm: A Rare Paraneoplastic Syndrome in an Infant With Hepatoblastoma
Authors: Vyas Neha , Neto Arino , Carakushansky Mauri , Gurnurkar Shilpa 
Published: June 2023

Abstract
Graves’ disease is the most common cause of pediatric hyperthyroidism and thyrotoxicosis. Thyroid storm is a rare initial manifestation of Graves’ disease and represents an endocrine emergency. We report a case of transient hyperthyroidism, possibly a paraneoplastic syndrome presenting as impending thyroid storm in a patient with undiagnosed hepatoblastoma. To our knowledge, this is the first case of this association reported in children. A previously healthy 21-month-old male presented with abdominal pain and unremitting tachycardia. He was managed for thyrotoxicosis and impending thyroid storm. He subsequently was found to have hepatomegaly leading to a diagnosis of hepatoblastoma. Autoimmune markers for Graves’ disease were negative, along with a negative human chorionic gonadotropin. After initiation of neoadjuvant chemotherapy, he had complete resolution of thyrotoxicosis. Paraneoplastic syndromes may occur with any tumor. We present a unique case of a patient developing human chorionic gonadotropin-negative hyperthyroidism, possibly as a paraneoplastic syndrome from hepatoblastoma.
Trending Ability of End-Tidal Capnography Monitoring During Mechanical Ventilation to Track Changes in Arterial Partial Pressure of Carbon Dioxide in Critically Ill Patients With Acute Brain Injury: A Monocenter Retrospective Study
Authors: Coëffic Adrien , Joachim Jona , Manquat Elsa , Felliot Élodie , Vallée Fabrice , Mebazaa Alexandre , Gayat Étienne , Chousterman Benjamin Glenn , Barthélémy Romain 
Published: June 2023

BACKGROUND:
Changes in arterial partial pressure of carbon dioxide (Paco
2) may alter cerebral perfusion in critically ill patients with acute brain injury. Consequently, international guidelines recommend normocapnia in mechanically ventilated patients with acute brain injury. The measurement of end-tidal capnography (Etco
2) allows its approximation. Our objective was to report the agreement between trends in Etco
2 and Paco
2 during mechanical ventilation in patients with acute brain injury.

METHODS:
Retrospective monocenter study was conducted for 2 years. Critically ill patients with acute brain injury who required mechanical ventilation with continuous Etco
2 monitoring and with 2 or more arterial gas were included. The agreement was evaluated according to the Bland and Altman analysis for repeated measurements with calculation of bias, and upper and lower limits of agreement. The directional concordance rate of changes between Etco
2 and Paco
2 was evaluated with a 4-quadrant plot. A polar plot analysis was performed using the Critchley methods.

RESULTS:
We analyzed the data of 255 patients with a total of 3923 paired ΔEtco
2 and ΔPaco
2 (9 values per patient in median). Mean bias by Bland and Altman analysis was −8.1 (95 CI, −7.9 to −8.3) mm Hg. The directional concordance rate between Etco
2 and Paco
2 was 55.8%. The mean radial bias by polar plot analysis was −4.4° (95% CI, −5.5 to −3.3) with radial limit of agreement (LOA) of ±62.8° with radial LOA 95% CI of ±1.9°.

CONCLUSIONS:
Our results question the performance of trending ability of Etco
2 to track changes in Paco
2 in a population of critically ill patients with acute brain injury. Changes in Etco
2 largely failed to follow changes in Paco
2 in both direction (ie, low concordance rate) and magnitude (ie, large radial LOA). These results need to be confirmed in prospective studies to minimize the risk of bias.
Efficient Algorithms for Stochastic Ride-Pooling Assignment with Mixed Fleets
Authors: Luo Qi , Nagarajan Viswanath , Sundt Alexander , Yin Yafeng , Vincent John , Shahabi Mehrdad 
Published: June 2023

Ride-pooling, which accommodates multiple passenger requests in a single trip, has the potential to substantially enhance the throughput of mobility-on-demand (MoD) systems. This paper investigates MoD systems that operate mixed fleets composed of “basic supply” and “augmented supply” vehicles. When the basic supply is insufficient to satisfy demand, augmented supply vehicles can be repositioned to serve rides at a higher operational cost. We formulate the joint vehicle repositioning and ride-pooling assignment problem as a two-stage stochastic integer program, where repositioning augmented supply vehicles precedes the realization of ride requests. Sequential ride-pooling assignments aim to maximize total utility or profit on a shareability graph: a hypergraph representing the matching compatibility between available vehicles and pending requests. Two approximation algorithms for midcapacity and high-capacity vehicles are proposed in this paper; the respective approximation ratios are [Formula: see text] and [Formula: see text], where p is the maximum vehicle capacity plus one. Our study evaluates the performance of these approximation algorithms using an MoD simulator, demonstrating that these algorithms can parallelize computations and achieve solutions with small optimality gaps (typically within 1%). These efficient algorithms pave the way for various multimodal and multiclass MoD applications. History: This paper has been accepted for the Transportation Science Special Issue on Emerging Topics in Transportation Science and Logistics. Funding: This work was supported by the National Science Foundation [Grants CCF-2006778 and FW-HTF-P 2222806], the Ford Motor Company, and the Division of Civil, Mechanical, and Manufacturing Innovation [Grants CMMI-1854684, CMMI-1904575, and CMMI-1940766]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/trsc.2021.0349 .