bluuebunny/crossref_metadata_2025_split huggingface dataset:
Letter the editor: serious methodological concerns about a recently published meta-analysis on oxygen therapy
Authors: Klitgaard Thomas Lass , Schjørring Olav Lilleholt , Nielsen Frederik Mølgaard , Meyhoff Christian Sylvest , Barbateskovic Marija , Wetterslev Jørn , Perner Anders , Rasmussen Bodil Steen 
Published: December 2021

AbstractIn a recent paper, Chen et al. report the findings of a systematic review with meta-analysis concerning conservative versus conventional oxygen therapy for critically ill patients. We wish to commend the authors for their interest in the matter. However, the authors appear to misquote findings, fail to report results for all specified analyses, do not identify all relevant trials, have post hoc changed the eligibility criteria, and have seemingly switched directions of effects in analyses of secondary outcomes. These issues have led to incorrect conclusions concerning the effects of targeted oxygen therapy in critically ill patients.
Automated alert and activation of medical emergency team using early warning score
Authors: Na Soo Jin , Ko Ryoung-Eun , Ko Myeong Gyun , Jeon Kyeongman 
Published: December 2021

Abstract
Background
Timely recognition of warning signs from deteriorating patients and proper treatment are important in improving patient safety. In comparison to the traditional medical emergency team (MET) activation triggered by phone calls, automated activation of MET may minimize activation delays. However, limited data are available on the effects of automated activation systems on the time from derangement to MET activation and on clinical outcomes. The objective of this study was to determine the impact of an automated alert and activation system for MET on clinical outcomes in unselected hospitalized patients.

Methods
This is an observational study using prospectively collected data from consecutive patients managed by the MET at a university-affiliated, tertiary hospital from March 2013 to December 2019. The automated alert system automatically calculates the Modified Early Warning Score (MEWS) and subsequently activates MET when the MEWS score is 7 or higher, which was implemented since August 2016. The outcome measures of interest including hospital mortality in patients with MEWS of 7 or higher were compared between pre-implementation and post-implementation groups of the automated alert and activation system in the primary analysis. The association between the implementation of the system and hospital mortality was evaluated with logistic regression analysis.

Results
Of the 7678 patients who were managed by MET during the study period, 639 patients during the pre-implementation period and 957 patients during the post-implementation period were included in the primary analysis. MET calls due to abnormal physiological variables were more common during the pre-implementation period, while MET calls due to medical staff’s worries or concern about the patient’s condition were more common during the post-implementation period. The median time from deterioration to MET activation was significantly shortened in the post-implementation period compared to the pre-implementation period (34 min vs. 60 min, P < 0.001). In addition, unplanned ICU admission rates (41.2% vs. 71.8%, P < 0.001) was reduced during the post-implementation period. Hospital mortality was decreased after implementation of the automated alert system (27.2% vs. 38.5%, P < 0.001). The implementation of the automated alert and activation system was associated with decreased risk of death in the multivariable analysis (adjusted OR 0.73, 95% CI 0.56–0.90).

Conclusions
After implementing an automated alert and activation system, the time from deterioration to MET activation was shortened and clinical outcomes were improved in hospitalized patients.
Sporadic E morphology based on COSMIC radio occultation data and its relationship with wind shear theory
Authors: Luo Jia , Liu Haifeng , Xu Xiaohua 
Published: December 2021

AbstractThe S4max data retrieved from the Constellation Observing System for the Meteorology, Ionosphere, and Climate (COSMIC) radio occultation (RO) measurements during 2007 to 2015 is adopted to investigate the global distribution and seasonal variation of the sporadic E (Es) layers in the present work. The long-term and short-term global Es occurrence maps are presented and the spatial and temporal distributions of Es occurrence rates (ORs) are further confirmed and studied. The International Geomagnetic Reference Field model (IGRF12) is used to calculate the horizontal intensity and inclination of the Earth’s magnetic field. The analysis shows that the Earth’s magnetic field is one of the fundamental reasons for the global distribution of the Es layers. In addition, the Horizontal Wind Field model HWM14 and the IGRF12 model were employed to calculate the vertical ion convergence (VIC) to examine the role of neutral wind shear in the global distribution of the Es ORs. The results reveal that the middle latitude distribution of simulated vertical concentration of Fe+ is similar to that of Es ORs, which indicates that the VIC induced by the neutral wind shear is an important factor in determining the geographical distribution, summer maximum (or winter minimum) and diurnal characteristics of Es ORs in middle latitudes. The new findings mainly include the following two aspects: (1) in summer over mid-latitudes, VIC peaks in the morning and afternoon to evening, which explains the semidiurnal behavior of Es ORs; (2) VIC reaches its minimum value in low-altitude (100 km) areas, which is the reason for the significant decrease in Es ORs in low-altitude areas. The disagreements between the VIC and Es ORs indicate that other processes, such as the meteor influx rate, the ionospheric electric fields and atmospheric tides, should also be considered as they may have an important impact on the variation of Es layers.
Graphical Abstract
Small-scale analysis to rank municipalities requiring slow-moving landslide risk mitigation measures: the case study of the Calabria region (southern Italy)
Authors: Gullà Giovanni , Nicodemo Gianfranco , Ferlisi Settimio , Borrelli Luigi , Peduto Dario 
Published: December 2021

AbstractThis paper proposes a three-phase method that combines multi-source (i.e. topographic, thematic, monitoring) input data in a GIS environment to rank—at small (1:250,000) scale—administrative units (e.g. municipalities) based on their exposure to slow-moving landslide risk within a selected area (e.g. a region) and, accordingly, detect those primarily requiring mitigation measures. The method is applied in the Calabria region (southern Italy) where several municipalities are widely affected by slow-moving landslides that systematically cause damage to buildings and infrastructure networks resulting in significant economic losses. The results obtained are validated based on the information gathered from previous studies carried out at large (municipal) scale. The work undertaken represents a first, fundamental step of a wider circular approach that can profitably facilitate the decision makers in addressing the issue of the slow-moving landslide risk mitigation in a sustainable way.
Results on patient-reported outcomes are underreported in summaries of product characteristics for new drugs
Authors: Haag Susanne , Junge Lisa , Lotz Fabian , McGauran Natalie , Paulides Marios , Potthast Regine , Kaiser Thomas 
Published: December 2021

Abstract
Background
Summaries of product characteristics (SmPCs) are regulatory documents published upon drug approval. They should report all relevant study data and advise how to use drugs safely and effectively. Patient-reported outcomes (PROs) are increasingly used in clinical trials to incorporate the patient perspective—SmPCs should thus adequately report PROs. In Germany, new drugs undergo mandatory early benefit assessment. Pharmaceutical companies submit dossiers containing all evidence; the subsequent dossier assessments focus on patient-relevant outcomes and comprehensively report PROs.

Objective
The primary aim was to investigate to what extent PROs recorded as outcomes in clinical trials of new drugs are reported in SmPCs.

Methods
We analysed dossier assessments with randomized controlled trials (RCTs) of new drugs entering the market between 01/2014 and 07/2018 and the corresponding SmPCs, and compared PRO reporting in both document types. For this purpose, we evaluated dossier assessment characteristics (e.g. drug name, indication, disease category) and study characteristics (e.g. evaluable PROs available?). PROs were divided into symptoms and health-related quality of life (HRQoL). SmPCs were screened to identify RCTs. We conducted 3 main evaluation steps: (1) Did the RCT included in the dossier assessment contain evaluable PROs? (2) If yes, was the RCT included in the SmPC? (3) If yes, were the PROs reported in the SmPC? Results are presented descriptively.

Results
88 dossier assessments including 143 RCTs on 72 drugs were considered: 109 (76.2%) RCTs included evaluable PROs, of which 89 were included in SmPCs. 38 RCTs (42.7%) investigated oncologics, 18 (20.2%) anti-infectives, and 33 (37.1%) other drugs. The RCTs considered symptoms more often than HRQoL (82 vs. 66 RCTs). In SmPCs, PROs were reported for 41 RCTs (46.1%), with a slightly higher reporting rate for RCTs considering HRQoL (43.9%) than for RCTs considering symptoms (41.5%). In oncologic indications, PROs were reported for 36.7% of RCTs considering HRQoL and 33.3% of RCTs considering symptoms. In infectious diseases, the rates were 21.4% (symptoms) and 0% (HRQoL), and for other diseases about 60% (symptoms) to 70% (HRQoL).

Conclusion
Even though a large amount of PRO data on new drugs is available from clinical trials included in SmPCs, the corresponding results are underreported.
Small Cell Undifferentiated Histology Does Not Adversely Affect Outcome in Hepatoblastoma: A Report From the Children's Oncology Group (COG) AHEP0731 Study Committee
Authors: Trobaugh-Lotrario Angela , Katzenstein Howard M. , Ranganathan Sarangarajan , Lopez-Terrada Dolores , Krailo Mark D. , Piao Jin , Chung Nadia , Randazzo Jessica , Malogolowkin Marcio H. , Furman Wayne L. , McCarville Elizabeth B. , Towbin Alexander J. , Tiao Greg M. , Dunn Stephen P. , Langham Max R. , McGahren Eugene D. , Feusner James , Rodriguez-Galindo Carlos , Meyers Rebecka L. , O'Neill Allison F. , Finegold Milton J. 
Published: December 2021

PURPOSE Small cell undifferentiated (SCU) histology in hepatoblastoma (HB) tumors has historically been associated with a poor prognosis. Tumors from patients enrolled on Children's Oncology Group (COG) study AHEP0731 underwent institutional and central pathologic review for identification of SCU histology. PATIENTS AND METHODS Patients with SCU histology identified at the local treating institution who had otherwise low-risk tumors were upstaged to the intermediate-risk treatment stratum, whereas those only identified by retrospective central review were treated per the local institution as low-risk. Patients with otherwise intermediate- or high-risk tumors remained in that treatment stratum, respectively. Central review was to be performed for all tissue samples obtained at any time point. Treatment was per local review, whereas analysis of outcome was based on central review. RESULTS Thirty-five patients had some elements (1%-25%) of SCU identified on central review of diagnostic specimens. All but two patient tissue sample retained nuclear INI1 expression. The presence of SCU histology did not correlate with age, alpha-fetoprotein level at diagnosis, or sex. The presence of SCU did not affect event-free survival (EFS). EFS at 5 years for patients with low-risk, intermediate-risk, and high-risk with SCU HB was 86% (95% CI, 33 to 98), 81% (95% CI, 57 to 92), and 29% (95% CI, 4 to 61), respectively, compared with EFS at 5 years for patients without SCU enrolled with low-risk, intermediate-risk, and high-risk of 87% (95% CI, 72 to 95), 88% (95% CI, 79 to 94), and 55% (95% CI, 32 to 74; P = .17), respectively. CONCLUSION The presence of SCU histology in HB does not appear to adversely affect outcome. Future studies should be able to treat patients with SCU HB according to risk stratification without regard to the presence of SCU histology.
Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03)
Authors: Gnant Michael , Dueck Amylou C. , Frantal Sophie , Martin Miguel , Burstein Hal J. , Greil Richard , Fox Peter , Wolff Antonio C. , Chan Arlene , Winer Eric P. , Pfeiler Georg , Miller Kathy D. , Colleoni Marco , Suga Jennifer M. , Rubovsky Gabor , Bliss Judith M. , Mayer Ingrid A. , Singer Christian F. , Nowecki Zbigniew , Hahn Olwen , Thomson Jacqui , Wolmark Norman , Amillano Kepa , Rugo Hope S. , Steger Guenther G. , Hernando Fernández de Aránguiz Blanca , Haddad Tufia C. , Perelló Antonia , Bellet Meritxell , Fohler Hannes , Metzger Filho Otto , Jallitsch-Halper Anita , Solomon Kadine , Schurmans Céline , Theall Kathy P. , Lu Dongrui R. , Tenner Kathleen , Fesl Christian , DeMichele Angela , Mayer Erica L. ,   on behalf of the PALLAS groups and investigators
Published: December 2021

PURPOSE Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor approved for advanced breast cancer. In the adjuvant setting, the potential value of adding palbociclib to endocrine therapy for hormone receptor–positive breast cancer has not been confirmed. PATIENTS AND METHODS In the prospective, randomized, phase III PALLAS trial, patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative early breast cancer were randomly assigned to receive 2 years of palbociclib (125 mg orally once daily, days 1-21 of a 28-day cycle) with adjuvant endocrine therapy or adjuvant endocrine therapy alone (for at least 5 years). The primary end point of the study was invasive disease-free survival (iDFS); secondary end points were invasive breast cancer–free survival, distant recurrence-free survival, locoregional cancer-free survival, and overall survival. RESULTS Among 5,796 patients enrolled at 406 centers in 21 countries worldwide over 3 years, 5,761 were included in the intention-to-treat population. At the final protocol-defined analysis, at a median follow-up of 31 months, iDFS events occurred in 253 of 2,884 (8.8%) patients who received palbociclib plus endocrine therapy and in 263 of 2,877 (9.1%) patients who received endocrine therapy alone, with similar results between the two treatment groups (iDFS at 4 years: 84.2% v 84.5%; hazard ratio, 0.96; CI, 0.81 to 1.14; P = .65). No significant differences were observed for secondary time-to-event end points, and subgroup analyses did not show any differences by subgroup. There were no new safety signals for palbociclib in this trial. CONCLUSION At this final analysis of the PALLAS trial, the addition of adjuvant palbociclib to standard endocrine therapy did not improve outcomes over endocrine therapy alone in patients with early hormone receptor–positive breast cancer.
A novel electrochemical synthesis of graphene oxide: Converting waste product to utility
Authors: Neog Ashamoni , Biswas Rajib , Bharali Nishant 
Published: December 2021

Abstract
We comprehensively report here a green route for synthesizing graphene oxide (GO) from waste Zn-C dry cell batteries. Here LiCl was used as electrolyte for the electrochemical synthesis of GO from graphite rods extracted from waste batteries. The satisfactory yield of 0.0305 g/h, formulated wholly through basic medium (at pH 9.36), was validated through confirmatory characterizations such as X-ray diffraction (XRD) analysis, Fourier-transform infrared spectroscopy (FTIR), UV-Vis and Raman spectroscopy, etc. A prominent diffraction peak around 26.70° in the XRD spectra and two prominent excitonic peaks around

and

in the Raman spectra were observed for the obtained samples. The overall scheme turned out to be engaging less reactants as well as facile; thus, converting a waste material to a useful product.
Ribociclib Cytotoxicity Alone or Combined With Progesterone and/or Mitotane in in Vitro Adrenocortical Carcinoma Cells
Authors: Abate Andrea , Rossini Elisa , Tamburello Mariangela , Laganà Marta , Cosentini Deborah , Grisanti Salvatore , Fiorentini Chiara , Tiberio Guido A M , Scatolini Maria , Grosso Enrico , Hantel Constanze , Memo Maurizio , Berruti Alfredo , Sigala Sandra 
Published: December 2021

Abstract
Mitotane is the only approved drug for treating adrenocortical carcinoma (ACC). The regimen added to mitotane is chemotherapy with etoposide, doxorubicin, and cisplatin. This pharmacological approach, however, has a limited efficacy and significant toxicity. Target-therapy agents represent a new promising approach to cancer therapy. Among these, a preeminent role is played by agents that interfere with cell-cycle progression, such as CDK4/6-inhibitors. Here, we investigate whether ribociclib could induce a cytotoxic effect both in ACC cell line and patient-derived primary cell cultures, alone or in combined settings. Cell viability was determined by 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide assay, whereas cell proliferation was evaluated by direct count. Binary combination experiments were performed using Chou and Talalay method. Gene expression was analyzed by quantitative RT-PCR, whereas protein expression was evaluated by immunofluorescence. A double staining assay revealed that ribociclib induced a prevalent apoptotic cell death. Cell-cycle analysis was performed to evaluate the effect of ribociclib treatment on cell-cycle progression in ACC cell models. Our results indicate that ribociclib was cytotoxic and reduced the cell proliferation rate. The effect on cell viability was enhanced when ribociclib was combined with progesterone and/or mitotane. The effect of ribociclib on cell-cycle progression revealed a drug-induced cell accumulation in G2 phase. The positive relationship underlined by our results between ribociclib, progesterone, and mitotane strengthen the clinical potential of this combination.
Oxygen-sensing mechanisms in development and tissue repair
Authors: Jiang Yida , Duan Li-Juan , Fong Guo-Hua 
Published: December 2021

ABSTRACT
Under normoxia, hypoxia inducible factor (HIF) α subunits are hydroxylated by PHDs (prolyl hydroxylase domain proteins) and subsequently undergo polyubiquitylation and degradation. Normal embryogenesis occurs under hypoxia, which suppresses PHD activities and allows HIFα to stabilize and regulate development. In this Primer, we explain molecular mechanisms of the oxygen-sensing pathway, summarize HIF-regulated downstream events, discuss loss-of-function phenotypes primarily in mouse development, and highlight clinical relevance to angiogenesis and tissue repair.
Ethics for "intelligent" beings created by man: scenarios of the future
Authors: Mijartovic Zorica , Jašić Orhan 
Published: December 2021

Artificial intelligence is a challenge for many scientists and researchers today. On the one hand, the development of artificial intelligence can be beneficial for people as it can significantly facilitate their daily lives and jobs. On the other hand, there is the fear that we will not succeed in developing "friendly artificial intelligence" and that these created intelligent beings becoming autonomous persons will bring many problems. Worries go so far as to assume that artificial intelligence will displace humans and take their place in all spheres of life. In this article, we have tried to present future scenarios concerning the development of artificial intelligence and indicate how necessary it is to have ethics in this discourse.Keywords: Artificial Intelligence, Algorithms, Bioethics, Ethics, Software, Science Fiction, Technology.
Brand Capital and Stock Price Crash Risk
Authors: Hasan Mostafa Monzur , Taylor Grantley , Richardson Grant 
Published: December 2021

We examine the relationship between brand capital and stock price crash risk. Crash risk, defined as the negative skewness in the distribution of returns for individual stocks, captures asymmetry in risk, and has important implications for investment choices and risk management. Using a sample of 39,685 publicly listed U.S. firm-year observations covering 1975 to 2018, we show that brand capital is significantly and negatively related to crash risk. We also use an advanced machine learning approach and confirm that brand capital is a strong predictor of future stock price crashes. Our cross-sectional analyses show that this negative relationship is more evident for subsamples with transitory poor earnings performance or persistent good earnings performance, greater corporate tax avoidance, and weak corporate governance structures. The results survive numerous robustness tests, including the use of alternative measures of brand capital, crash risk, and several endogeneity tests. In sum, our findings are consistent with agency theory, suggesting that high levels of brand capital expose firms to investor and customer scrutiny, which reduces managerial opportunistic behavior that may include the accumulation and concealment of negative information. This paper was accepted by Karl Diether, finance.
Quo Vadis Kebijakan Affirmative Action dalam Sistem Demokrasi di Indonesia
Authors: Oktaviani Amelia , Megawati Megawati 
Published: December 2021

Secara umum adanya penelitian ini ditujukan untuk mengetahui bagaimana pelaksanaan kebijakan affirmative action di Indonesia dan apakah pelaksanaan tersebut mencerminkan nilai-nilai keadilan beserta kendala-kendala apa saja dalam pelaksanaan kebijakan affirmative action tersebut. Dari hasil penelitian yuridis normatif ini menemukan fakta bahwaÂ kebijakan affirmative action di Indonesia sendiri telah mulai diterapkan sejak pemilihan umum 2004 lalu. Akan tetapi dari sejak awal kebijakan tersebut diterapkan hingga saat ini belum pernah ada satu pun pemilihan umum yang berhasil mencapai angka 30 % keterwakilan perempuan di lembaga legislatif. Selain itu, pelaksanaan kebijakan affirmative action pun belum sepenuhnya dapat mencerminkan nilai-nilai keadilan. Di sisi lain, pelaksanaan kebijakan affirmative action juga terkendala oleh faktor sosio-kultural dan struktural seperti masih tertanam kuatnya budaya patriarki di masyarakat, adanya stereotipe terhadap perempuan, adanya beban ganda yang dipikul oleh perempuan, kurangnya modal politik, sosial dan ekonomi perempuan, adanya model politik yang masih sangat maskulin, belum optimalnya fungsi partai politik dan kurangnya political will untuk memperkuat regulasi dan implementasi kebijakan affirmative action dalam sistem demokrasi di Indonesia.