bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico and in vitro analysis of a rational mutation in gIII signal peptide and its effects on periplasmic expression of rhGH in E. coli
Authors: Ghasemi Fahimeh , Zare Hamed , Zomorodipour Alireza , Shirzeyli Maryam Hosseinzade , Kieliszek Marek 
Published: August 2022

AbstractThe secretion efficiency of a heterologous protein in E. coli is mainly dictated by the N-terminal signal peptide fused to the desired protein. In this study, we aimed to select and introduce mutations into the – 1, – 2 and – 3 positions of the gIII signal peptide (originated from filamentous phage fd Gene III) fused to the N-terminus of the human growth hormone (hGH), and study its effect on the secretion efficiency of the recombinant hGH into the periplasmic space of E. coli Top10. Bioinformatics software such as SignalP-5.0 and PrediSi were employed to predict the effects of the mutations on the secretion efficiency of the recombinant hGH. Site-directed mutagenesis was applied to introduce the desired mutations into the C-terminus of the gIII signal peptide. The periplasmic expression and the secretion efficiency of the recombinant hGH using the native and mutant gIII signal peptides were compared in E. coli Top10 under the control of araBAD promoter. Our results from bioinformatics analysis indicated that the mutant gIII signal peptide was more potent than the native one for secretion of the recombinant hGH in E. coli. While our experimental results revealed that the mutation had no effect on hGH secretion. This result points to the importance of experimental validation of bioinformatics predictions.
A framework for establishing scientific confidence in new approach methodologies
Authors: van der Zalm Anna J. , Barroso João , Browne Patience , Casey Warren , Gordon John , Henry Tala R. , Kleinstreuer Nicole C. , Lowit Anna B. , Perron Monique , Clippinger Amy J. 
Published: August 2022

AbstractRobust and efficient processes are needed to establish scientific confidence in new approach methodologies (NAMs) if they are to be considered for regulatory applications. NAMs need to be fit for purpose, reliable and, for the assessment of human health effects, provide information relevant to human biology. They must also be independently reviewed and transparently communicated. Ideally, NAM developers should communicate with stakeholders such as regulators and industry to identify the question(s), and specified purpose that the NAM is intended to address, and the context in which it will be used. Assessment of the biological relevance of the NAM should focus on its alignment with human biology, mechanistic understanding, and ability to provide information that leads to health protective decisions, rather than solely comparing NAM-based chemical testing results with those from traditional animal test methods. However, when NAM results are compared to historical animal test results, the variability observed within animal test method results should be used to inform performance benchmarks. Building on previous efforts, this paper proposes a framework comprising five essential elements to establish scientific confidence in NAMs for regulatory use: fitness for purpose, human biological relevance, technical characterization, data integrity and transparency, and independent review. Universal uptake of this framework would facilitate the timely development and use of NAMs by the international community. While this paper focuses on NAMs for assessing human health effects of pesticides and industrial chemicals, many of the suggested elements are expected to apply to other types of chemicals and to ecotoxicological effect assessments.
Collaborative behaviour and coalitions in male jaguars (Panthera onca)—evidence and comparison with other felids
Authors: Jędrzejewski Włodzimierz , Hoogesteijn Rafael , Devlin Allison L. , Tortato Fernando , Concone Henrique Villas Boas , Azevedo Fernando , Eriksson Charlotte E. , Fragoso Carlos Eduardo , Abarca Maria , Morato Ronaldo G. , Giordano Anthony J. , Hoogesteijn Almira , Rampim Lilian , Gamarra Gertrudis , Carreño Rafael , Velásquez Grisel , Schmidt Krzysztof 
Published: August 2022

Abstract
Most large felids are classified as solitary species, with only lions (Panthera leo) and cheetahs (Acinonyx jubatus) exhibiting social, collaborative behaviours. Herein, we present evidence of the formation of male coalitions by jaguars (Panthera onca), based on data from five studies conducted with camera trapping, GPS telemetry, and direct observations in the Venezuelan Llanos and Brazilian Pantanal. Out of 7062 male records obtained with camera traps or visual observations, we detected 105 cases of male-male interactions, of which we classified 18 as aggression, nine as tolerance, 70 as cooperation/coalition, and eight as unidentified. In two studies, two male jaguars formed stable coalitions lasting over 7 years each. In the Llanos, each coalition male paired and mated with several females. For male jaguar coalitions, we documented similar behaviours as recorded earlier in lions or cheetahs, which included patrolling and marking territory together, invading territories of other males, collaborative chasing and killing other jaguars, and sharing prey. However, different from lions or cheetahs, associated male jaguars spent less time together, did not cooperate with females, and did not hunt cooperatively together. Our analysis of literature suggested that male jaguar coalitions were more likely to form when females had small home range size, a proxy of females’ concentration, while in lions, the male group size was directly correlated with the female group size. Similarly, locally concentrated access to females may drive formation of male coalitions in cheetahs. We conclude that high biomass and aggregation of prey are likely drivers of sociality in felids.

Significance statement
The division into social and solitary species in large felids has so far seemed unambiguous, with only lions and cheetahs classified as social species, in which male coalitions also occurred. Our data show that, under certain conditions, male coalitions may also form in jaguar populations. Factors that drive formation of male coalitions in lions and cheetahs, but not in other species of large cats, have not been clear until now. Our analyses indicate that in jaguars, lions, and cheetahs, the concentration of females likely plays the most important role. In jaguars, the probability of male coalition occurrence is highest in populations with the smallest mean female home range size (and thus likely high local density of females), while in lions, male group size is most strongly correlated with female group size.
Evaluation of an artificial intelligence coronary artery calcium scoring model from computed tomography
Authors: Ihdayhid Abdul Rahman , Lan Nick S. R. , Williams Michelle , Newby David , Flack Julien , Kwok Simon , Joyner Jack , Gera Sahil , Dembo Lawrence , Adler Brendan , Ko Brian , Chow Benjamin J. W. , Dwivedi Girish 
Published: August 2022

Abstract
Objectives
Coronary artery calcium (CAC) scores derived from computed tomography (CT) scans are used for cardiovascular risk stratification. Artificial intelligence (AI) can assist in CAC quantification and potentially reduce the time required for human analysis. This study aimed to develop and evaluate a fully automated model that identifies and quantifies CAC.

Methods
Fully convolutional neural networks for automated CAC scoring were developed and trained on 2439 cardiac CT scans and validated using 771 scans. The model was tested on an independent set of 1849 cardiac CT scans. Agatston CAC scores were further categorised into five risk categories (0, 1–10, 11–100, 101–400, and > 400). Automated scores were compared to the manual reference standard (level 3 expert readers).

Results
Of 1849 scans used for model testing (mean age 55.7 ± 10.5 years, 49% males), the automated model detected the presence of CAC in 867 (47%) scans compared with 815 (44%) by human readers (p = 0.09). CAC scores from the model correlated very strongly with the manual score (Spearman’s r = 0.90, 95% confidence interval [CI] 0.89–0.91, p < 0.001 and intraclass correlation coefficient = 0.98, 95% CI 0.98–0.99, p < 0.001). The model classified 1646 (89%) into the same risk category as human observers. The Bland–Altman analysis demonstrated little difference (1.69, 95% limits of agreement: −41.22, 44.60) and there was almost excellent agreement (Cohen’s κ = 0.90, 95% CI 0.88–0.91, p < 0.001). Model analysis time was 13.1 ± 3.2 s/scan.

Conclusions
This artificial intelligence–based fully automated CAC scoring model shows high accuracy and low analysis times. Its potential to optimise clinical workflow efficiency and patient outcomes requires evaluation.

Key Points
• Coronary artery calcium (CAC) scores are traditionally assessed using cardiac computed tomography and require manual input by human operators to identify calcified lesions.
• A novel artificial intelligence (AI)–based model for fully automated CAC scoring was developed and tested on an independent dataset of computed tomography scans, showing very high levels of correlation and agreement with manual measurements as a reference standard.
• AI has the potential to assist in the identification and quantification of CAC, thereby reducing the time required for human analysis.
Low bone mineral density is a prognostic factor for elderly patients with HCC undergoing TACE: results from a multicenter study
Authors: Müller Lukas , Mähringer-Kunz Aline , Auer Timo Alexander , Fehrenbach Uli , Gebauer Bernhard , Haubold Johannes , Theysohn Jens M. , Kim Moon-Sung , Kleesiek Jens , Diallo Thierno D. , Eisenblätter Michel , Bettinger Dominik , Steinle Verena , Mayer Philipp , Zopfs David , Pinto dos Santos Daniel , Kloeckner Roman 
Published: August 2022

Abstract
Objectives
Low bone mineral density (BMD) was recently identified as a novel risk factor for patients with hepatocellular carcinoma (HCC). In this multicenter study, we aimed to validate the role of BMD as a prognostic factor for patients with HCC undergoing transarterial chemoembolization (TACE).

Methods
This retrospective multicenter trial included 908 treatment-naïve patients with HCC who were undergoing TACE as a first-line treatment, at six tertiary care centers, between 2010 and 2020. BMD was assessed by measuring the mean Hounsfield units (HUs) in the midvertebral core of the 11th thoracic vertebra, on contrast-enhanced computer tomography performed before treatment. We assessed the influence of BMD on median overall survival (OS) and performed multivariate analysis including established estimates for survival.

Results
The median BMD was 145 HU (IQR, 115–175 HU). Patients with a high BMD (≥ 114 HU) had a median OS of 22.2 months, while patients with a low BMD (< 114 HU) had a lower median OS of only 16.2 months (p < .001). Besides albumin, bilirubin, tumor number, and tumor diameter, BMD remained an independent prognostic factor in multivariate analysis.

Conclusions
BMD is an independent predictive factor for survival in elderly patients with HCC undergoing TACE. The integration of BMD into novel scoring systems could potentially improve survival prediction and clinical decision-making.

Key Points
• Bone mineral density can be easily assessed in routinely acquired pre-interventional computed tomography scans.
• Bone mineral density is an independent predictive factor for survival in elderly patients with HCC undergoing TACE.
• Thus, bone mineral density is a novel imaging biomarker for prognosis prediction in elderly patients with HCC undergoing TACE.
Enhanced linear and nonlinear optical properties of erbium/ytterbium lead phosphate glass by gamma irradiation for optoelectronics applications
Authors: Sallam O. I. , Abdel Maksoud M. I. A. , Kassem Said M. , Awed A. S. , Elalaily N. A. 
Published: August 2022

AbstractHerein, this study intends to reveal the impact of gamma irradiation on the structural, linear, and nonlinear optical characteristics of 47P2O5−23Na2O−6Al2O3−22PbO−0.5Er2O3−1.5Yb2O3glass. The Er/Yb-doped lead phosphate glass samples were produced using the traditional melt quenching procedure and then treated to different doses of gamma irradiation (0, 20, 50, and 100) kGy. The amorphous phase structure of the Er/Yb-doped lead phosphate glass samples was verified through XRD patterns. Also, the shift of the FTIR peaks due to the change in bond angles, and the change in the bond length of the P–O–P bridges means the glass network stability against radiation. With increasing irradiation dosages, the energy gap dropped from 4.11 eV to 3.42 eV and then enhanced to 3.48 at 100 kGy. At the same time, the Urbach energy enhanced from 10.23 eV to 37.03 eV. The oscillator energy Eo was found between 1.55 and 1.62 eV. Also, the dispersion energy Edvaried between 2.11 eV at 100 kGy and 2.71 eV at the dose of 50 kGy. The percentage of free carrier ions to effective mass (N/m*) is in the range (4.82–8.66) × 1047cm3/g. Besides, the lattice dielectric constant ($${\varepsilon }_{l}$$εl) increased from 5.54 to 6.63 as the gamma dosages increased. Furthermore, increasing gamma doses up to 50 kGy promotes susceptibility, which subsequently declines at 100 kGy, suggesting that increasing gamma doses over 50 kGy weakens polarizability potential. While the increasing gamma doses up to 50 kGy reduces the nonlinear refractive index and then improves at 100 kGy. Overall, the nonlinear and linear research revealed that Er/Yb lead phosphate glass is being used as a promising material for gain media and optical amplifiers.
Venting during venoarterial extracorporeal membrane oxygenation
Authors: Lüsebrink Enzo , Binzenhöfer Leonhard , Kellnar Antonia , Müller Christoph , Scherer Clemens , Schrage Benedikt , Joskowiak Dominik , Petzold Tobias , Braun Daniel , Brunner Stefan , Peterss Sven , Hausleiter Jörg , Zimmer Sebastian , Born Frank , Westermann Dirk , Thiele Holger , Schäfer Andreas , Hagl Christian , Massberg Steffen , Orban Martin 
Published: August 2022

AbstractCardiogenic shock and cardiac arrest contribute pre-dominantly to mortality in acute cardiovascular care. Here, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as an established therapeutic option for patients suffering from these life-threatening entities. VA-ECMO provides temporary circulatory support until causative treatments are effective and enables recovery or serves as a bridging strategy to surgical ventricular assist devices, heart transplantation or decision-making. However, in-hospital mortality rate in this treatment population is still around 60%. In the recently published ARREST trial, VA-ECMO treatment lowered mortality rate in patients with ongoing cardiac arrest due to therapy refractory ventricular fibrillation compared to standard advanced cardiac life support in selected patients. Whether VA-ECMO can reduce mortality compared to standard of care in cardiogenic shock has to be evaluated in the ongoing prospective randomized studies EURO-SHOCK (NCT03813134) and ECLS-SHOCK (NCT03637205). As an innate drawback of VA-ECMO treatment, the retrograde aortic flow could lead to an elevation of left ventricular (LV) afterload, increase in LV filling pressure, mitral regurgitation, and elevated left atrial pressure. This may compromise myocardial function and recovery, pulmonary hemodynamics—possibly with concomitant pulmonary congestion and even lung failure—and contribute to poor outcomes in a relevant proportion of treated patients. To overcome these detrimental effects, a multitude of venting strategies are currently engaged for both preventive and emergent unloading. This review aims to provide a comprehensive and structured synopsis of existing venting modalities and their specific hemodynamic characteristics. We discuss in detail the available data on outcome categories and complication rates related to the respective venting option.
Graphical abstract
FLOT and CROSS chemotherapy regimens alter the frequency of CD27+ and CD69+ T cells in oesophagogastric adenocarcinomas: implications for combination with immunotherapy
Authors: Davern Maria , Donlon Noel E. , Sheppard Andrew S. , Majcher Klaudia D. , Connell Fiona O’ , Heeran Aisling B. , Grant Malika , Farrell Robert A. , Hayes Conall , Bracken-Clarke Dara , Conroy Melissa J. , Foley Emma , Toole Dermot O’ , Bhardwaj Anshul , Ravi Narayanasamy , Reynolds John V. , Maher Stephen G. , Sullivan Jacintha O’ , Lysaght Joanne 
Published: August 2022

AbstractCombining immunostimulatory chemotherapies with immunotherapy is an attractive strategy to enhance treatment responses in oesophagogastric junctional adenocarcinoma (OGJ). This study investigates the immunostimulatory properties of FLOT, CROSS and MAGIC chemotherapy regimens in the context of OGJ using in vitro and ex vivo models of the treatment-naïve and post-chemotherapy treated tumour microenvironment. FLOT and CROSS chemotherapy regimens increased surrogate markers of immunogenic cell death (HMGB1 and HLA-DR), whereas the MAGIC treatment regimen decreased HMGB1 and HLA-DR on OGJ cells (markedly for epirubicin). Tumour-infiltrating and circulating T cells had significantly lower CD27 expression and significantly higher CD69 expression post-FLOT and post-CROSS treatment. Similarly, the supernatant from FLOT- and CROSS-treated OGJ cell lines and from FLOT- and CROSS-treated OGJ biopsies cultured ex vivo also decreased CD27 and increased CD69 expression on T cells. Following 48 h treatment with post-FLOT and post-CROSS tumour conditioned media the frequency of CD69+ T cells in culture negatively correlated with the levels of soluble immunosuppressive pro-angiogenic factors in the conditioned media from ex vivo explants. Supernatant from FLOT- and CROSS-treated OGJ cell lines also increased the cytotoxic potential of healthy donor T cells ex vivo and enhanced OGJ patient-derived lymphocyte mediated-killing of OE33 cells ex vivo. Collectively, this data demonstrate that FLOT and CROSS chemotherapy regimens possess immunostimulatory properties, identifying these chemotherapy regimens as rational synergistic partners to test in combination with immunotherapy and determine if this combinatorial approach could boost anti-tumour immunity in OGJ patients and improve clinical outcomes.
Lower limb post-traumatic osteomyelitis: a systematic review of clinical outcomes
Authors: Rodham Paul , Panteli Michalis , Vun James S. H. , Harwood Paul , Giannoudis Peter V. 
Published: August 2022

Abstract
Purpose
The aim of this study was to examine the patient-reported outcomes of patients presenting with post-traumatic osteomyelitis (PTOM) of the lower limb over the past 15 years. This period was chosen to reflect modern treatment principles and increased centralisation of care.

Methods
An electronic literature search of the relevant databases (PubMed, Ovid Medline, Embase, and the Cochrane library) was conducted to identify studies published between January 2006 and July 2021 reporting series of greater than 10 patients with PTOM of the tibia or femur at the site of a previous fracture. Studies reporting septic non-union were excluded.

Results
Sixteen eligible studies were identified and included in the final report. Remission of infection was achieved in 93.2% of cases (range 70–100%), whilst amputation was reported in 1–7% of cases. A variety of patient-reported outcome measures were utilised including the lower extremity functional scale, short musculoskeletal functional assessment, Enneking score, and EQ-5D-3L. Limb-specific functional outcomes returned to levels similar to that of the general population although poorer outcomes were noted in specific cohorts including those with complex anatomic disease and active medical comorbidities.

Conclusion
Infection following fracture fixation remains a difficult problem to treat. Regardless, using modern treatments and techniques patients can have comparable functional outcomes to that of the general population. High-quality studies are required to advance our knowledge into which types of treatments offer a benefit and how to further improve outcomes.
Training is not enough: child and adolescent psychiatry clinicians’ impressions of telepsychiatry during the first COVID-19 related lockdown
Authors: Rusu Vlad-Alexandru , van der Lans R. M. , Vermeiren R. R. J. M. , Hauber K. , de Lijster J. M. , Lindauer R. J. L. , Nugter A. , Hoekstra P. J. , Nooteboom L. A. 
Published: August 2022

AbstractTo ensure the continuity of care during the COVID-19 pandemic, clinicians in Child and Adolescent Psychiatry (CAP) were forced to immediately adapt in-person treatment into remote treatment. This study aimed to examine the effects of pre-COVID-19 training in- and use of telepsychiatry on CAP clinicians’ impressions of telepsychiatry during the first two weeks of the Dutch COVID-19 related lockdown, providing a first insight into the preparations necessary for the implementation and provision of telepsychiatry during emergency situations. All clinicians employed by five specialized CAP centres across the Netherlands were invited to fill in a questionnaire that was specifically developed to study CAP clinicians’ impressions of telepsychiatry during the COVID-19 pandemic. A total of 1065 clinicians gave informed consent and participated in the study. A significant association was found between pre-COVID-19 training and/or use of telepsychiatry and CAP clinicians’ impressions of telepsychiatry. By far, the most favourable impressions were reported by participants that were both trained and made use of telepsychiatry before the pandemic. Participants with either training or use separately reported only slightly more favourable impressions than participants without any previous training or use. The expertise required to provide telepsychiatry is not one-and-the-same as the expertise that is honed through face-to-face consultation. The findings of this study strongly suggest that, separately, both training and (clinical) practice fail to sufficiently support CAP clinicians in the implementation and provision of telepsychiatry. It is therefore recommended that training and (clinical) practice are provided in conjunction.
Investigation and numerical simulation of debris flow events in Rochefort basin (Aosta Valley—NW Italian Alps) combining detailed geomorphological analyses and modern technologies
Authors: Vagnon Federico , Kurilla Laurie Jayne , Clusaz Alain , Pirulli Marina , Fubelli Giandomenico 
Published: August 2022

AbstractThis paper presents a multidisciplinary approach using modern technologies for the analysis and modelling of the debris flow that occurred at Torrent Rochefort (Aosta Valley—Italy) September 2015. A detailed on-site geological and geomorphological study was performed to highlight the main characteristics of the basin, useful for validating and calibrating dynamic simulations. The total mobilized volume was estimated by comparing a pre-event DTM and a post-event DTM generated from an unmanned aerial vehicle. A digital terrain model comparative analysis provided a quantitative estimation of erodible depths in different sectors of the Rochefort basin. Numerical modelling of the event was performed using the continuum mechanics-based code RASH3D that enabled a simulation of the dynamic debris motion on complex topography. The results demonstrate the importance of a detailed geomorphological study for the validation and calibration of numerical results. Finally, some considerations were inferred about the magnitude of unstable debris and the possible consequences on local infrastructures.