bluuebunny/crossref_metadata_2025 huggingface dataset:
A Milestone or Mistake of Progress? The Death Penalty and State Consolidation in Austria and Czechoslovakia after 1918
Authors: Šmidrkal Václav
Published: February 2022

This article takes a comparative approach and deals with the issue of the death penalty in Austria and Czechoslovakia after the First World War. Whereas both successor states strived for progressive reforms that would delimit them from the discredited old regime, each of them found a different response to the experience of extreme violence and massive use of the death penalty during the First World War. While Austria abolished the death penalty by law in 1919 and anchored this abolition into its constitution in 1920, Czechoslovakia, despite expectations to the contrary, gradually embedded this punishment within the process of national state consolidation in the post-war chaos. This article argues that this difference was not only a result of an actual dominance of retentionists or abolitionists, but it had its deeper roots in the relation of the new states to the vanquished empire and the values of the regime change. Austrian Social Democrats, alongside other politicians, saw a way out of the state collapse and the post-war legal nihilism through laying down the state's new foundations and by the abolishing the death penalty, which they regarded as unjustifiable. In Czechoslovakia the death penalty was dismissed as a means of national repression under the Habsburgs but it proved useful in maintaining military discipline in the Czechoslovak Army and managing its peripheral regions where the state had little representation. It also served as a penal instrument to control the skyrocketing criminality that occurred amidst the post-war chaos. While the misery of defeat called for a fresh start in Austria, the death penalty turned out to be irreplaceable for securing the national independence and future prospects in victorious Czechoslovakia.
Comparison between Del Nido and conventional blood cardioplegia in pediatric open-heart surgery
Authors: Floh Alejandro A , Das Shubhadeep , Haranal Maruti , Laussen Peter C , Crawford-Lean Lynn , Fan Chun-Po S , Mertens Luc L , Runeckles Kyle , Honjo Osami
Published: February 2022

Background

Del Nido cardioplegia (DNc) was designed for superior myocardial protection during cardiopulmonary bypass (CPB). We conducted a retrospective review to explore if DNc was associated with increase in systemic ventricle dysfunction (sVD) following pediatric CPB.

Methods and Results

This single-center, retrospective study included 1534 patients undergoing CPB between 2013 and 2016, 997 prior to center-wide conversion to DNc and 537 following. The primary outcome was new postoperative ≥moderate sVD by echocardiogram. Secondary outcomes included sVD of any severity and right ventricular dysfunction. Data was evaluated by interrupted time-series analysis. Groups had similar cardiac diagnoses and surgical complexity. Del Nido cardioplegia was associated with longer median (IQR) CPB [117 (84–158) vs 108 (81–154), p = 0.04], and aortic cross-clamp [83 (55–119) vs 76 (53–106), p = 0.03], and fewer cardioplegia doses [2 (1–2) vs 3 (2–4), p < 0.0001]. Mortality was similar in both groups. Frequency of sVD was unchanged following DNc, including predetermine subgroups (neonates, infants, and prolonged cross-clamp). Logistic regression showed a significant rise in right ventricular dysfunction (OR 5.886 [95% CI: 0.588, 11.185], p = 0.03) but similar slope.

Conclusions

Use of DNc was not associated with increased in reported sVD, and provided similar myocardical protection to the systemic ventricle compared to conventional cardioplegia but may possibly impact right ventricular function. Studies evaluating quantitative systolic and diastolic function are needed.
Increased capillary stalling is associated with endothelial glycocalyx loss in subcortical vascular dementia
Authors: Yoon Jin-Hui , Shin Paul , Joo Jongyoon , Kim Gaon S , Oh Wang-Yuhl , Jeong Yong
Published: February 2022

Proper regulation and patency of cerebral microcirculation are crucial for maintaining a healthy brain. Capillary stalling, i.e., the brief interruption of microcirculation has been observed in the normal brain and several diseases related to microcirculation. We hypothesized that endothelial glycocalyx, which is located on the luminal side of the vascular endothelium and involved in cell-to-cell interaction regulation in peripheral organs, is also related to cerebral capillary stalling. We measured capillary stalling and the cerebral endothelial glycocalyx (cEG) in male mice using in vivo optical coherence tomography angiography (OCT-A) and two-photon microscopy. Our findings revealed that some capillary segments were prone to capillary stalling and had less cEG. In addition, we demonstrated that the enzymatic degradation of the cEG increased the capillary stalling, mainly by leukocyte plugging. Further, we noted decreased cEG along with increased capillary stalling in a mouse model of subcortical vascular dementia (SVaD) with impaired cortical microcirculation. Moreover, gene expression related to cEG production or degradation changed in the SVaD model. These results indicate that cEG mediates capillary stalling and impacts cerebral blood flow and is involved in the pathogenesis of SVaD.
Improved sintering performance of β-SiAlON–Si3N4 and its osteogenic differentiation ability by adding β-SiAlON
Authors: Mu Jinghua , Zhang Liguo , Zhang Can , Xu Enxia , Wang Lulu , Liu Xinhong , Chang Guanglei , Sun Xu , Ma Chengliang , Yuan Huiyu , Zhao Fei , Gao Jinxing
Published: February 2022

To improve the sintering performance of silicon nitride bioceramics, we explored the effect of β-SiAlON’s Z-value on the physical, chemical, and biological properties of β-SiAlON–Si3N4 composites. Results showed that the phase product was β-Si3N4. As the Z-value increased, the X-ray diffraction peaks gradually shifted to a smaller angle, the material grains were more tightly packed, and the bulk density and compressive strength increased, reaching the highest values (2.71 g/cm3 and 1157 MPa, respectively) at Z = 4. Soaking and ion-release experiments show that in an aqueous environment, a small amount of Al and Si ions were released, and no obvious decomposition occurred on the surface of the material. The biological performance showed that the growth of cultured cells in each group was in good condition, there was no obvious difference in morphology and adhesion, and the materials had good biological performance. An increase in the Z-value promotes the formation of mineralized nodules and osteogenic differentiation of MC3T3-E1 cells, which may be because the release of Si can promote osteogenic differentiation. Therefore, the addition of β-SiAlON could improve the sintering performance of β-Si3N4 without degrading its biological properties. The prepared β-SiAlON–Si3N4 composite ceramic is a latent bioceramic material.
Modeling the patient mix for risk-adjusted CUSUM charts
Authors: Wittenberg Philipp
Published: February 2022

The improvement of surgical quality and the corresponding early detection of its changes is of increasing importance. To this end, sequential monitoring procedures such as the risk-adjusted CUmulative SUM chart are frequently applied. The patient risk score population (patient mix), which considers the patients’ perioperative risk, is a core component for this type of quality control chart. Consequently, it is important to be able to adapt different shapes of patient mixes and determine their impact on the monitoring scheme. This article proposes a framework for modeling the patient mix by a discrete beta-binomial and a continuous beta distribution for risk-adjusted CUSUM charts. Since the model-based approach is not limited by data availability, any patient mix can be analyzed. We examine the effects on the control chart’s false alarm behavior for more than 100,000 different scenarios for a cardiac surgery data set. Our study finds a negative relationship between the average risk score and the number of false alarms. The results indicate that a changing patient mix has a considerable impact and, in some cases, almost doubles the number of expected false alarms.
Linking External Knowledge Search to Innovation Ambidexterity in SMEs
Authors: Ryu Dongwoo , Baek Kwang Ho , Yoon Junghyun
Published: February 2022

The purpose of this study is to investigate the effect of external knowledge search strategy on innovation ambidexterity for SMEs. In order to achieve the purpose of research, hypotheses were set up by dividing exploitative knowledge sources and exploitative knowledge. Based on the Tobit regression analysis results by using the 975 data of Science and Technology Policy Institute, this research provides four findings as follows: First, exploitative knowledge breadth positively and significantly influences innovation ambidexterity. Second, exploitative knowledge depth positively and significantly influences innovation ambidexterity. Third, explorative knowledge breadth positively and significantly influences innovation ambidexterity. Lastly, the relationship between explorative knowledge significantly influences innovation ambidexterity. The results indicate that their knowledge search strategies ware significant driver of their innovation ambidexterity. In the final conclusion section implications and limitations of research results and suggestion for future research are discussed.
The Macroeconomic Impact of Fiscal Policy Shocks: What do the Indian Data Say?
Authors: Sobti Riddhima
Published: February 2022

This article examines the impact of fiscal policy shocks on a set of macroeconomic variables in India, using a seasonally adjusted quarterly dataset for the period 2003–2019. The Gregory-Hansen residual-based test for cointegration and the vector error correction model (VECM) are applied, and impulse responses based on a recursive identification scheme (Cholesky decomposition) is used to assess the effects of a gross tax revenue shock and a government spending shock on economic activity, while accounting for the possibility of structural breaks. The findings indicate that an unexpected fiscal policy shock has an immediate expansionary impact on real GDP and a sudden positive effect on inflation (WPI) and the repo rate; and that the impact is permanent and away from the zero equilibrium. The careful design of policies by the central bank and the government as crucial macroeconomic stabilisation tools is imperative.

JEL Classification: E6, H20, H30
Burnout and Burnt Breakfast: A Clinician and Educator’s Perspective
Authors: Midha Monica
Published: February 2022

It is clear that burnout is on the rise among physicians. 1 And while there are articles detailing areas that could be addressed, 2 change takes time, and progress on a large scale is slow. While we watch the system evolve, we have to take accountability for our own personal well-being. We cannot sit around and wait for the whole industry to change when we can have control over our own circumstances. I sat down to analyze my own stressors and think about their impact on my work–life balance. Stress will continue to exist and evolve, but we can grow from it and shift from negativity to positivity to continue improving our own well-being. As an educator, this is particularly important in ensuring the well-being of future generations.
Protective effects of the notoginsenoside R1 on acute lung injury by regulating the miR-128-2-5p/Tollip signaling pathway in rats with severe acute pancreatitis
Authors: He Ju , Liu Ming-wei , Wang Zhi-yi , Shi Rong-jie
Published: February 2022

Notoginsenoside R1 (NG-R1), the extract and the main ingredient of Panax notoginseng, has anti-inflammatory effects and can be used in treating acute lung injury (ALI). In this study, we explored the pulmonary protective effect and the underlying mechanism of the NG-R1 on rats with ALI induced by severe acute pancreatitis (SAP). MiR-128-2-5p, ERK1, Tollip, HMGB1, TLR4, IκB, and NF-κB mRNA expression levels were measured using real-time qPCR, and TLR4, Tollip, HMGB1, IRAK1, MyD88, ERK1, NF-κB65, and P-IκB-α protein expression levels using Western blot. The NF-κB and the TLR4 activities were determined using immunohistochemistry, and TNF-α, IL-6, IL-1β, and ICAM-1 levels in the bronchoalveolar lavage fluid (BALF) using ELISA. Lung histopathological changes were observed in each group. NG-R1 treatment reduced miR-128-2-5p expression in the lung tissue, increased Tollip expression, inhibited HMGB1, TLR4, TRAF6, IRAK1, MyD88, NF-κB65, and p-IκB-α expression levels, suppressed NF-κB65 and the TLR4 expression levels, reduced MPO activity, reduced TNF-α, IL-1β, IL-6, and ICAM-1 levels in BALF, and alleviated SAP-induced ALI. NG-R1 can attenuate SAP-induced ALI. The mechanism of action may be due to a decreased expression of miR-128-2-5p, increased activity of the Tollip signaling pathway, decreased activity of HMGB1/TLR4 and ERK1 signaling pathways, and decreased inflammatory response to SAP-induced ALI. Tollip was the regulatory target of miR-128-2-5p.
What reading Montaigne during the Second World War can teach us about just war
Authors: Brunstetter Daniel R
Published: February 2022

Revisionist just war scholarship employs the rigors of analytical philosophy to make arguments about the deep morality of war. Accepting the individual and cosmopolitan are paramount to making sense of war as many revisionists do, this essay looks outside the just war canon to Montaigne—a sixteenth century French humanist hailed for his exploration of the self and cosmopolitan musings—for alternative insights. It explores how Montaigne was read during the Second World War by three intellectuals to make sense of war: Stefan Zweig, Jean Guéhenno, and François Mauriac. While Montaigne’s skepticism and turn to the self as an act of preservation was, in the 1930s, rejected as a strategy to combat rising authoritarianism in Europe by philosophers such as Max Horkheimer of the Frankfurt school, the thinkers studied here shed light on Montaigne as a source of active humanism based in reflective action that leads to Resistance. Building on trends in just war thinking that call for paying greater attention to the lived experience of war, the article identifies several psychological and moral processes—the inward turn, the cosmopolitan gaze, casting an existential anchor, and the humanist’s wager—to shed light on the doubt-laden process of making individual moral choices amidst the rising dogmatic forces that war tends to impose.
Efficacy of excision versus ablation for improving endometriosis related pain: A systematic review and meta-analysis
Authors: Ouyang Chensi , Fitch Amy , Cho Kelly S , Driscoll Jenna , Wang Alexander , Lamvu Georgine
Published: February 2022

Background:

Surgical treatment of superficial peritoneal endometriosis includes excision or ablation. Controversy exists about which method is better for providing pain relief. We performed a meta-analysis of randomized control trials (RCTs) comparing the efficacy of excision versus ablation for improving the most frequently encountered endometriosis pain symptoms: dysmenorrhea, dyspareunia, non-cyclic pelvic pain, and dyschezia.

Methods:

A search from inception to May 2020 was conducted in PubMed, MEDLINE, Clinicaltrials.gov, Cochrane Central Register of Controlled Trials, and Web of Science. RCTs comparing excision versus ablation for peritoneal endometriosis were included if they assessed dysmenorrhea, dyspareunia, dyschezia, and pelvic pain/non-menstrual pain. Exclusion criteria included extra-peritoneal endometriosis or endometriomas, and non-English publications. Publications were assessed for risk of bias and quality of evidence using Cochrane risk of bias tool (RoB 2) and GradePro.

Results:

Of the 2025 records identified initially, four met inclusion criteria. The sample sizes of the included studies ranged from 24 to 133 participants. The excision and ablation groups included 204 participants each. There was no difference after excision or ablation for dysmenorrhea when comparing the mean change in pain scores from baseline to 12 months after surgery (−0.31, 95% CI −1.66, 1.04, p = 0.65), dyspareunia (−0.24, 95% CI −1.78, 1.30, p = 0.76), dyschezia (−0.72, 95% CI −1.94, 0.50, p = 0.25), or non-cyclic pain (−0.78, 95% CI −2.47, 0.91, p = 0.37).

Conclusions:

We found low to moderate quality evidence suggesting that neither excision nor ablation is superior in reduction of endometriosis-related pain up to 12 months after surgery.
Why the Aryans Still Matter? History, Historiography and Politics
Authors: Kumar Ashish
Published: February 2022

This review article ponders over the debate on the river Sarasvati’s association with the Harappan civilization through a critical analysis of G. D. Bakshi’s book The Sarasvati Civilization: A Paradigm Shift in Ancient Indian History (2019, Gurugram: Garuda Prakashan). By identifying the Rigvedic river Sarasvati with the now dry Ghaggar-Hakra, scholars like G. D. Bakshi co-relate the Vedic-Aryan culture with the Harappans and, by doing this, they Aryanize the Harappan civilization. Since the Aryans are accepted as the ancestors of the modern Hindus, by locating the origin of the Aryans within India, right-leaning scholars put forth the exclusive claim of the Hindu community over the Indian nation. Contrary to them, the left-liberal scholars endorse the Aryan migration theory, and it allows them to explain the origin of the Indian civilization due to the contribution of different ethnic, linguistic and cultural groups that have had migrated into India from faraway lands. It is argued in this review paper that the Aryan debate is more about politics than academic endeavour, and its primarily focus is on the following question: Who has a righteous claim over the Indian nation?
Basic Amenity and the Caste Conundrum: A Study of the Dalit Communities in East Uttar Pradesh
Authors: Malik Bibhuti Bhushan , Kumar Ajay
Published: February 2022

Dalits lack the bare necessities, such as living in substandard houses with constrained space and rooms devoid of the kitchen, bathroom, and sanitation facilities; with a minuscule living area and limited access to safe drinking water. These aspects of civic amenities are empirically examined with qualitative and quantitative approach in east Uttar Pradesh using significant variables such as housing conditions, access to safe drinking water and toilet availability in households. The article also discuss the dimension and level of civic amenities in Dalit households. Based on research-based field data and ethnography, poverty and a lack of civic amenities are the convoluted pathways and fundamental causes of Dalit families living in poor health, unhygienic conditions and without sanitation. The explanation justifies how Dalits’ lack of public amenities, particularly in micro-settlements, intentionally manifests organized caste identity.
Political Economy of Dispossession and Economic Change: A Case of Rajarhat in West Bengal, India
Authors: Roy Animesh
Published: February 2022

Land dispossession under the neoliberal capitalist development has become a focal point of debate across Indian states, particularly in West Bengal. Based on household surveys conducted in Rajarhat in West Bengal (India) in 2009 and 2016, this article illuminates how a large-scale dispossession of farmers from land for a neoliberal planned urban centre adjoining Kolkata Metropolis leads to a process of economic change and rural transformation, giving birth to diverse non-farm livelihood activities for the dispossessed households. While access to these new livelihood opportunities in the burgeoning urban economy turns out to be unequal, the dispossessed households broadly undergo upward economic mobility. It also argues that the benefits of speculative land value arising from neoliberalisation of spaces in the post-acquisition stage actuate the partially dispossessed households to sell off their remaining land and produce a basis for social differentiations and asset inequalities within the dispossessed households. To prevent these and similar outcomes, it calls for apt policies.
Measuring circularity: evaluation of the circularity of construction products using the ÖKOBAUDAT database
Authors: Dräger Philipp , Letmathe Peter , Reinhart Linda , Robineck Florian
Published: February 2022

Background

Owing to the large amounts of energy, greenhouse gases, and waste that it generates, the construction industry is fundamental to the transition towards a circular economy. Indicators which show the circularity of products—and thus make them comparable with each other—can be used to support the implementation of such an economy. In this article, we have adapted the material circularity indicator of the Ellen MacArthur Foundation in order to analyze the circularity of construction products available in the German environmental database ÖKOBAUDAT.

Results

The adapted indicator is applied to 89 building products from the categories of insulation materials, plastics, metals, and mineral building materials. More than half of the products receive the lowest score of 0.10, indicating poor implementation of circular strategies in the German construction industry to date.

Conclusion

Circular material flows are most likely to be employed for metals. However, the overall low circularity scores indicate a big need for better implementing circularity strategies.
Real world risk of infusion reactions and effectiveness of front-line obinutuzumab plus chlorambucil compared with other frontline treatments for chronic lymphocytic leukemia
Authors: Bourrier Nicole , Landego Ivan , Bucher Oliver , Squires Mandy , Streu Erin , Hibbert Irena , Whiteside Theresa , Gibson Spencer B. , Geirnaert Marc , Johnston James B. , Dawe David E. , Banerji Versha
Published: February 2022

Background

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in North America. Previous studies have shown improved progression free survival (PFS) and response rates in unfit patients treated with obinutuzumab compared to other regimens. The aim of this study was to evaluate the obinutuzumab-chlorambucil regimen in the context of historical treatments and first-dose infusion reactions at CancerCare Manitoba (CCMB).

Methods

A retrospective chart review was conducted for patients treated with obinutuzumab from January 1, 2014 to December 31, 2017 at CCMB. A minimum data set was extracted for patients treated with other front-line therapies. Descriptive statistics were used to evaluate patient demographics, toxicity, duration and dosing of obinutuzumab treatment. Kaplan–Meier curves were used to evaluate time-to-next-treatment (TTNT), overall survival (OS) and PFS for patients treated with obinutuzumab. A multivariable logistic regression model was used to investigate associations between infusion related reactions (IRRs) and age at treatment, pre-treatment lymphocyte count, cumulative illness rating scale (CIRS) and receipt of prior chemotherapy.

Results

Forty seven percent of patients receiving frontline therapy received chlorambucil and obinutuzumab. Sixty-seven patients were treated with obinutuzumab and consisted of 36 males (53.7%) and 31 females (46.3%) with 29 patients (43.3%) over age 75 years. Rates of grade 3 and 4 obinutuzumab IRRs were lower (6%) compared to the CLL11 clinical trial (20%) due to local practices including slower infusion rates and using chlorambucil before starting obinutuzumab treatment. Many patients had difficulty tolerating the full dosage of chlorambucil. Only 26 patients (38.8%) had their dose of chlorambucil escalated to the full dose of 0.5 mg/kg. In addition, only 18 patients (26.9%) received all doses of obinutuzumab and all 12 doses of chlorambucil.

Conclusions

In summary, first dose infusion reactions with obinutuzumab can be markedly reduced by using chlorambucil to decrease the lymphocyte count before obinutuzumab and by using a very slow initial obinutuzumab infusion rate. Modifications in chlorambucil dosing and obinutuzumab administration can improve tolerance without significant loss in efficacy.
Building organisations, setting minds: exploring how boards of Dutch medical specialist companies address physicians’ professional performance
Authors: Debets Maarten P. M. , Silkens Milou E. W. M. , Kruijthof Karen C. J. , Lombarts Kiki M. J. M. H.
Published: February 2022

Background

Governments worldwide are reforming healthcare systems to achieve high quality and safe patient care while maintaining costs. Self-employed physicians reorganise into novel organisations to meet reconfiguration demands, impacting their work environment and practice. This study explores what strategies these novel organisations use to address physicians’ professional performance and what they encounter when executing these strategies to achieve high quality and safe care.

Methods

This constructivist exploratory qualitative study used focus groups to answer our research question. Between October 2018 and May 2019, we performed eight focus group sessions with purposively sampled Medical Specialist Companies (MSCs), which are novel physician-led organisations in the Netherlands. In each session, board members of an MSC participated (n = 33).

Results

MSCs used five strategies to address physicians’ professional performance: 1) actively managing and monitoring performance, 2) building a collective mindset, 3) professionalising selection and onboarding, 4) improving occupational well-being, and 5) harmonising working procedures. The MSC’s unique context determined which strategies and quality and safety topics deserved the most attention. Physicians’ support, trusting relationships with hospital administrators, and the MSC’s organisational maturity seem critical to the quality of the strategies’ execution.

Conclusions

The five strategies have clear links to physicians’ professional performance and quality and safety. Insight into whether an MSC’s strategies together reflect medical professional or organisational values seems crucial to engage physicians and collaboratively achieve high quality and safe care.
DIX domain containing 1 (DIXDC1) modulates VEGFR2 level in vasculatures to regulate embryonic and postnatal retina angiogenesis
Authors: Kim Yeaji , Kim Dong Young , Zhang Haiying , Bae Cho-Rong , Seong Daehyeon , Kim Yeomyung , Song Jaewhan , Kim Young-Myeong , Kwon Young-Guen
Published: February 2022

Background

In sprouting angiogenesis, VEGFR2 level is regulated via a fine-tuned process involving various signaling pathways. Other than VEGF/VEGFR2 signaling pathway, Wnt/ β-catenin signaling is also important in vascular development. However, the crosstalk between these two signaling pathways is still unknown to date. In this study, we aimed to investigate the role of DIX domain containing 1 (DIXDC1) in vasculature, facilitating the crosstalk between VEGF/VEGFR2 and Wnt/ β-catenin signaling pathways.

Results

In mice, DIXDC1 deficiency delayed angiogenesis at the embryonic stage and suppressed neovascularization at the neonatal stage. DIXDC1 knockdown inhibited VEGF-induced angiogenesis in endothelial cells in vitro by downregulating VEGFR2 expression. DIXDC1 bound Dishevelled Segment Polarity Protein 2 (Dvl2) and polymerized Dvl2 stabilizing VEGFR2 protein via its direct interaction. The complex formation and stability of VEGFR2 was potentiated by Wnt signaling. Moreover, hypoxia elevated DIXDC1 expression and likely modulated both canonical Wnt/β-catenin signaling and VEGFR2 stability in vasculatures. Pathological angiogenesis in DIXDC1 knockout mice was decreased significantly in oxygen-induced retinopathy (OIR) and in wound healing models. These results suggest that DIXDC1 is an important factor in developmental and pathological angiogenesis.

Conclusion

We have identified DIXDC1 as an important factor in early vascular development. These results suggest that DIXDC1 represents a novel regulator of sprouting angiogenesis that links Wnt signaling and VEGFR2 stability and may have a potential role in pathological neovascularization.
Identification of recurrent genetic patterns from targeted sequencing panels with advanced data science: a case-study on sporadic and genetic neurodegenerative diseases
Authors: Tarozzi M. , Bartoletti-Stella A. , Dall’Olio D. , Matteuzzi T. , Baiardi S. , Parchi P. , Castellani G. , Capellari S.
Published: February 2022

Background

Targeted Next Generation Sequencing is a common and powerful approach used in both clinical and research settings. However, at present, a large fraction of the acquired genetic information is not used since pathogenicity cannot be assessed for most variants. Further complicating this scenario is the increasingly frequent description of a poli/oligogenic pattern of inheritance showing the contribution of multiple variants in increasing disease risk. We present an approach in which the entire genetic information provided by target sequencing is transformed into binary data on which we performed statistical, machine learning, and network analyses to extract all valuable information from the entire genetic profile. To test this approach and unbiasedly explore the presence of recurrent genetic patterns, we studied a cohort of 112 patients affected either by genetic Creutzfeldt–Jakob (CJD) disease caused by two mutations in the PRNP gene (p.E200K and p.V210I) with different penetrance or by sporadic Alzheimer disease (sAD).

Results

Unsupervised methods can identify functionally relevant sources of variation in the data, like haplogroups and polymorphisms that do not follow Hardy–Weinberg equilibrium, such as the NOTCH3 rs11670823 (c.3837 + 21 T > A). Supervised classifiers can recognize clinical phenotypes with high accuracy based on the mutational profile of patients. In addition, we found a similar alteration of allele frequencies compared the European population in sporadic patients and in V210I-CJD, a poorly penetrant PRNP mutation, and sAD, suggesting shared oligogenic patterns in different types of dementia. Pathway enrichment and protein–protein interaction network revealed different altered pathways between the two PRNP mutations.

Conclusions

We propose this workflow as a possible approach to gain deeper insights into the genetic information derived from target sequencing, to identify recurrent genetic patterns and improve the understanding of complex diseases. This work could also represent a possible starting point of a predictive tool for personalized medicine and advanced diagnostic applications.
MCM6 versus Ki-67 in diagnosis of luminal molecular subtypes of breast cancers
Authors: Sadeghian Dorsay , Saffar Hana , Mahdavi Sharif Pouya , Soleimani Vahid , Jahanbin Behnaz
Published: February 2022

Background

Currently, breast cancers are divided into four major molecular subtypes. The distinction between the luminal A and luminal B subtypes is mainly based on the cellular proliferation indices and is assessed by the Ki-67 scoring. Due to the limitations in the assessment and expression of Ki-67, we hypothesized that minichromosome maintenance protein 6 (MCM6) might be taken as a surrogate marker to differentiate molecular subtypes and aid in more precise grading of tumors.

Methods

We performed a retrospective, cross-sectional study on 124 samples of breast cancer and 40 samples of normal breast tissue. Relevant clinical information was retrieved from the Cancer Institute database.

Results

MCM6 could discriminate between various categories of histologic grades, tubule formation, mitotic indices, and nuclear pleomorphism (P = 0.002 for tubule formation andP < 0.001 for other). Moreover, the MCM6 score exhibited a significant correlation with the mitotic count (P < 0.001). However, the Ki-67 score could not discriminate subgroups of the mitotic index and nuclear pleomorphism. Compared to the luminal A subtype, luminal B exhibited a higher MCM6 score (P = 0.01). Besides, MCM6 scores were higher for certain subtypes with more aggressive behaviors, such as hormone receptor (HR)-negative disease, and human epidermal growth factor receptor 2 (HER2)-enriched and triple-negative breast cancers, as there was a significantly higher MCM6 mean score in the HR-negative in comparison to the luminal breast cancers (P < 0.001). Similarly, higher MCM6 scores were observed among samples with more advanced nuclear grades, tubule formation, and overall grades.

Conclusion

MCM6 can differentiate luminal A and luminal B subtypes and is correlated with mitotic counts. However, this study was unable to prove the superiority of MCM6 in differentiating between molecular subtypes compared to the Ki-67 score. Nevertheless, in our study, MCM6 was superior to Ki-67 in exhibiting correlations with the mitotic grade, tubule formation, and nuclear grades. More studies are needed to standardize its assessment methods, determine more robust cut-off values, and evaluate its associations with prognostic features of breast cancer.
Vasospasm following low-velocity penetrating pediatric intracranial trauma
Authors: Almojuela Alysa , Kaderali Zul , McEachern James , Kazina Colin , Serletis Demitre
Published: February 2022

Background

BB guns or non-powder guns created in the modern era are able to reach exceedingly fast velocities as a result of advances in compressed-gas technology. While missile penetrating trauma has been well documented in neurosurgical literature, penetrating intracranial injury secondary to non-powder guns, along with their associated complications and treatments, is not well described, and even less so in the pediatric population.

Case presentation

Here, we describe an unusual case of a 6-year-old Indigenous child who was accidentally shot with a BB gun to the head. He subsequently developed delayed acute right-sided weakness due to symptomatic vasospasm. His symptoms resolved following hypertensive therapy, balloon angioplasty intervention, and intra-arterial milrinone therapy.

Conclusions

This case highlights the unique complication of delayed symptomatic vasospasm in a child following a non-missile intracranial penetrating injury. Intracranial vasospasm needs to be considered in the presence of delayed neurological deficit given its potential reversibility. This case also emphasizes the importance of gun safety and education when handling and storing these potential weapons around children.
Barriers and facilitators associated with the use of mental health services among immigrant students in high-income countries: a scoping review protocol
Authors: Dombou Christelle , Omonaiye Olumuyiwa , Fraser Sarah , Cénat Jude Mary , Yaya Sanni
Published: February 2022

Background

While the mental health of immigrants is a growing issue that is attracting increasing interest from researchers, the same cannot be said for the mental health of immigrant students especially for international students. Indeed, the mental health of immigrant students and their use of mental health services are still poorly documented despite the significant increase in the number of these students in many high-income countries. This scoping review aims to providing an overview and exploring gaps in existing research regarding access to mental health care among immigrant students by identifying barriers and facilitators associated with the use of mental health services in high-income countries.

Methods

With the help of a professional librarian, we will develop a search strategy including several keywords such as mental health, mental illness, immigrant, students, immigrant students, or international students and access to care or use of mental health services. The following electronic databases will be searched (from their inception onwards): MEDLINE, APA PsycINFO, CINAHL, Web of Science Core Collection, Education Source, and Embase. Studies addressing access to and use of mental health care conducted on immigrant students (adolescent and above) in high-income countries will be included. Two reviewers will independently screen all citations, full-text articles, and abstract data. A narrative summary of findings will be conducted. Data analysis will involve quantitative (e.g., frequencies) and qualitative (e.g., content and thematic analysis) methods.

Discussion

The purpose of this scoping review is to better map the literature on the mental health of immigrant students and their use of mental health care services. In doing so, we aim to identify barriers and facilitators to access and use of mental health care. Identifying barriers and facilitators of mental health services by immigrant students will support the development of appropriate interventions that can help improve access and use of mental health services by immigrant students in high-income countries.

Systematic review registration

Open Science Framework (osf.io/a2rk6)
Economic purification of recombinant uricase by artificial oil bodies
Authors: Saadat Fatemeh , Macheroux Peter , Alizadeh Houshang , Razavi Seyed Hadi
Published: February 2022

Rasburicase is an expensive treatment used to control hyperuricemia caused by tumour lysis syndrome (TLS). In this study, a non-chromatographic method was designed based on nano-oil bodies for convenient and economical purification of the recombinant uricase. For this purpose, two chimaeras were synthesized with a different arrangement of the uricase, caleosin and intein fragments. After confirming the protein expression by measuring the uricase activity at 293 nm, purification was conducted through oil-body construction. The results were resolved on the 12% SDS-PAGE gel. Finally, the stability of the oil bodies was examined against different salts, surfactants, temperatures, and pH values. According to our results, the overexpression of uricase–caleosin chimaera under the T7 promoter in Escherichia coli led to the production of soluble protein, which was successfully purified by artificial oil bodies. The active uricase was subsequently released through the self-splicing of intein. Further investigations highlighted the importance of the free C-terminus of caleosin in constructing artificial oil bodies. Moreover, surfactants and low temperature, in contrast to salts, improved the stability of oil bodies. In conclusion, caleosins are an efficient purification tag reducing the cost of purification compared to conventional chromatography methods.

Graphical Abstract
Predicting the Likelihood of Carrying a BRCA1 or BRCA2 Mutation in Asian Patients With Breast Cancer
Authors: Ang Boon Hong , Ho Weang Kee , Wijaya Eldarina , Kwan Pui Yoke , Ng Pei Sze , Yoon Sook Yee , Hasan Siti Norhidayu , Lim Joanna M.C. , Hassan Tiara , Tai Mei-Chee , Allen Jamie , Lee Andrew , Taib Nur Aishah Mohd , Yip Cheng Har , Hartman Mikael , Lim Swee Ho , Tan Ern Yu , Tan Benita K.T. , Tan Su-Ming , Tan Veronique K.M. , Ho Peh Joo , Khng Alexis J. , Dunning Alison M. , Li Jingmei , Easton Douglas F. , Antoniou Antonis C. , Teo Soo Hwang
Published: February 2022

PURPOSE

With the development of poly (ADP-ribose) polymerase inhibitors for treatment of patients with cancer with an altered BRCA1 or BRCA2 gene, there is an urgent need to ensure that there are appropriate strategies for identifying mutation carriers while balancing the increased demand for and cost of cancer genetics services. To date, the majority of mutation prediction tools have been developed in women of European descent where the age and cancer-subtype distributions are different from that in Asian women.

METHODS

In this study, we built a new model (Asian Risk Calculator) for estimating the likelihood of carrying a pathogenic variant in BRCA1 or BRCA2 gene, using germline BRCA genetic testing results in a cross-sectional population-based study of 8,162 Asian patients with breast cancer. We compared the model performance to existing mutation prediction models. The models were evaluated for discrimination and calibration.

RESULTS

Asian Risk Calculator included age of diagnosis, ethnicity, bilateral breast cancer, tumor biomarkers, and family history of breast cancer or ovarian cancer as predictors. The inclusion of tumor grade improved significantly the model performance. The full model was calibrated (Hosmer-Lemeshow P value = .614) and discriminated well between BRCA and non- BRCA pathogenic variant carriers (area under receiver operating curve, 0.80; 95% CI, 0.75 to 0.84). Addition of grade to the existing clinical genetic testing criteria targeting patients with breast cancer age younger than 45 years reduced the proportion of patients referred for genetic counseling and testing from 37% to 33% ( P value = .003), thereby improving the overall efficacy.

CONCLUSION

Population-specific customization of mutation prediction models and clinical genetic testing criteria improved the accuracy of BRCA mutation prediction in Asian patients.
Levels and Correlates of Objectively Measured Sedentary Behavior in Young Children: SUNRISE Study Results from 19 Countries
Authors: KARIIPPANON KATHARINA E. , CHONG KAR HAU , JANSSEN XANNE , TOMAZ SIMONE A. , RIBEIRO EVELYN H. C. , MUNAMBAH NYARADZAI , CHAN CECILIA H. S. , CHATHURANGANA PW PRASAD , DRAPER CATHERINE E. , EL HAMDOUCHI ASMAA , FLORINDO ALEX A. , GUAN HONGYAN , HA AMY S. , HOSSAIN MOHAMMAD SOROWAR , KIM DONG HOON , VAN KIM THANH , KOH DENISE C. L. , LÖF MARIE , PHAM BANG NGUYEN , POH BEE KOON , REILLY JOHN J. , STAIANO AMANDA E. , SUHERMAN ADANG , TANAKA CHIAKI , TANG HONG KIM , TREMBLAY MARK S. , WEBSTER E. KIPLING , WICKRAMASINGHE V. PUJITHA , WONG JYH EIIN , OKELY ANTHONY D.
Published: February 2022

Purpose

There is a paucity of global data on sedentary behavior during early childhood. The purpose of this study was to examine how device-measured sedentary behavior in young children differed across geographically, economically, and sociodemographically diverse populations, in an international sample.

Methods

This multinational, cross-sectional study included data from 1071 children 3–5 yr old from 19 countries, collected between 2018 and 2020 (pre-COVID). Sedentary behavior was measured for three consecutive days using activPAL accelerometers. Sedentary time, sedentary fragmentation, and seated transport duration were calculated. Linear mixed models were used to examine the differences in sedentary behavior variables between sex, country-level income groups, urban/rural settings, and population density.

Results

Children spent 56% (7.4 h) of their waking time sedentary. The longest average bout duration was 81.1 ± 45.4 min, and an average of 61.1 ± 50.1 min·d−1 was spent in seated transport. Children from upper-middle–income and high-income countries spent a greater proportion of the day sedentary, accrued more sedentary bouts, had shorter breaks between sedentary bouts, and spent significantly more time in seated transport, compared with children from low-income and lower-middle–income countries. Sex and urban/rural residential setting were not associated with any outcomes. Higher population density was associated with several higher sedentary behavior measures.

Conclusions

These data advance our understanding of young children’s sedentary behavior patterns globally. Country income levels and population density appear to be stronger drivers of the observed differences, than sex or rural/urban residential setting.
Curative intent Stereotactic Ablative Radiation Therapy (SABR) for treatment of lung oligometastases from head and neck squamous cell carcinoma (HNSCC): a multi-institutional retrospective study
Authors: Debbi Kamel , Loganadane Gokoulakrichenane , To Nhu Hanh , Kinj Remy , Husain Zain A , Chapet Sophie , Nguyen Nam P , Barillot Isabelle , Benezery Karen , Belkacemi Yazid , Calais Gilles
Published: February 2022

Objectives:

The aim of this retrospective study was to assess outcomes of SABR for metachronous isolated lung oligometastases from HNSCC.

Methods:

For patients who developed isolated, 1 or 2 lungs lesions (<5cm) consistent with metastases from HNSCC, the indication of SABR was validated in a multidisciplinary tumor board. All patients were monitored by CT or PET CT after SABR (Stereotactic Ablative Body Radiation) for HNSCC.

Results:

Between November 2007 and February 2018, 52 patients were treated with SABR for metachronous lung metastases. The median time from the treatment of the primary HNSCC to the development of lung metastases was 18 months (3-93). The cohort’s median age was 65.5 years old (50-83). The vast majority (94.2%) received 60 Gy in three fractions. Forty-one patients (78.5%) presented a solitary lung metastasis, while 11 patients (21.5%) had two lung metastases. With a median follow-up of 45.3 months, crude local and metastatic control rates were 74 and 38%, respectively. 1 year and 2 year Overall Survival (OS) were 85.8 and 65.9%, respectively. The median OS was 46.8 months. About one-fourth of patients were retreated by SABR for distant pulmonary recurrence. The treatment was well tolerated with only one patient who reported ≥ grade 3 toxicity (1.9%).

Conclusion:

In selected metastatic HNSCC patients, early detection and treatment of lung metastases with SABR is effective and safe. Prospective studies are required to validate this potential shift.

Advances in knowledge:

Patients with oligometastases and controlled primary HNSCC seem to benefit from metastasis directed therapies.
Impact of bowel dilation on small bowel motility measurements with cine-MRI: assessment of two quantification techniques
Authors: van Rijn Kyra L , Stoker Jaap , Menys Alex , de Jonge Catharina S
Published: February 2022

Objectives:

To evaluate the effect of bowel dilation on cine-MRI small bowel motility measurements, by comparing a conventional motility score (including bowel wall and lumen) with a bowel wall-specific motility score in healthy and diseased populations.

Methods:

Four populations were included: 10 Crohn’s patients with a stricture and prestricture dilation for segmental motility analysis, and 14 mannitol-prepared healthy subjects, 15 fasted healthy subjects and eight chronic intestinal pseudo-obstruction (CIPO) patients (characterized by dilated bowel loops) for global small bowel motility analysis. All subjects underwent a cine-MRI scan from which two motility scores were calculated: a conventional score (including bowel wall and lumen) and a bowel wall-specific score. The difference between the two scores was calculated per population and compared between groups with a one-way ANOVA and Tukey-Kramer analysis.

Results:

In Crohn’s patients, the median (IQR) change between the conventional and wall-specific motility score was 0% (-2 to +4%) within the stricture and 0% (−1 to +7%) in the prestricture dilation. For the global small bowel, this was −1% (−5 to 0%) in mannitol-prepared healthy subjects, −2% (−6 to +2%) in fasted healthy subjects and +14% (+6 to+20%) in CIPO patients. The difference between the two motility scores in CIPO patients differed significantly from the four other groups (p = 0.002 to p < 0.001).

Conclusions:

The conventional small bowel motility score seems robust in Crohn’s disease patients and healthy subjects. In patients with globally and grossly dilated bowel loops, a bowel-wall specific motility score may give a better representation of small bowel motility.

Advances in knowledge:

These findings support researchers and clinicians with making informed choices for using cine-MRI motility analysis in different populations.