bluuebunny/crossref_metadata_2025 huggingface dataset:
Populism, Liberalism and the Eclipse of Emotion
Authors: Bird-Pollan Stefan
Published: October 2021

I argue that the way philosophy conceives of the political subject fails to understand the populist subject. In Section I, I shall sketch an ambiguity in how Hobbes conceives of the political subject as both driven by the passions and yet capable of rationally subduing them. In Section II, I argue that these two different conceptions of the will lead to different models of political representation. In Section III, I offer an sketch of some of the ways the Hobbesian picture of the mind as fueled by the passions has been eschewed by modern liberal philosophy. Finally, in Section IV, I offer an account of two features of populism which seem to me to suggest that the Humean model of the will is appropriate to understand certain essential features of populist politics.
COVID-19 Restrictions in Ireland – Has There Been an Impact on the Welfare of Sport and Leisure Horses?
Authors: McKeon Katie Ann , Walsh Elizabeth Ann
Published: October 2021

Horses form an integral part of Irish culture and heritage. COVID-19 restrictions have created challenges for living generally and for those who own and care-take animals. It is envisaged that risks may arise for equine welfare and many factors may contribute to it. The “Five Freedoms” have formed the basis for animal welfare legislation however, the “Five Domains Model” has progressed to provide a robust model built on scientific research. With advances in research and knowledge, welfare may be measured both physiologically and behaviourally. This study sought to investigate the impact, if any of COVID-19, on the welfare of sport and leisure horses in Ireland. An online survey was conducted to gather data regarding the welfare of sport and leisure horses in Ireland during COVID-19 restrictions. There were several positive findings and the majority of respondents (n = 69) felt that COVID-19 restrictions did not negatively affect the welfare of their horses.
Nones and Catholics in Quebec
Authors: Meunier E.-Martin , Legault-Leclair Jacob
Published: October 2021

The authors examine the relationship between religion and support for State secularism in the context of the recent passing of Bill 21 in Quebec. After contextualizing the transformation of Québécois’ regime of religiosity from the 1960s to the present day, the authors analyze two surveys on how the restrictive measures set out in Bill 21 have been received and supported. Public opinion data suggest something unexpected at first glance: support for the measures aimed at restricting the wearing of religious symbols in State institutions appears to come mainly from Francophones who are self-declared Catholics, rather than from the nonreligious. Language, religious (non) affiliation, age as well as place of residence appear to be major determinants when it comes to support for the restrictive State secularism measures.
Nothing Is Not Something
Authors: Cragun Ryan T. , McCaffree Kevin
Published: October 2021

With the advance of secularization in numerous countries and the growth of those who report no religious affiliation, more attention is being given to individuals who are not religious. Various scholars have proposed names for the individuals who report no religious affiliation and researchers have created categories for such individuals. The de facto term is now “nonreligion” or “nonreligious.” However, even when the term “nonreligious” (Lee 2012) was put forward, there were serious reservations about labeling a group of people by what they are not. In this article, we detail why this is such a serious problem, and how this is only going to become more of a problem as this segment of national populations grows. We propose that we discontinue referring to such individuals as “nonreligious” and instead focus on the positive substance of their identities.
Rethinking the Textual Value of 4Q11 (4QpaleoGen-Exodl)
Authors: Dayfani Hila
Published: October 2021

This paper focuses on a fragmentary copy of Exodus from Qumran that has not so far received sufficient attention—4Q11 (4QpaleoGen-Exodl). The paper proposes a material reconstruction of the scroll and discusses its contribution to the textual classification of the scroll. Although 4Q11 apparently reflects the short literary form of MT and LXX Exodus, which does not include the major expansions characteristic of the pre-Samaritan tradition, an examination of individual readings reveals that the scroll includes some minor exegetical variants. Thus, 4Q11 demonstrates the necessity of exploring the scribal approach reflected in scriptural Qumran scrolls, in addition to their classification into textual traditions. Only such a holistic investigation can allow for an improved understanding of the text and processes that took place during its transmission.
Compromise and Defence: Great Britain and the Burma Road Crisis
Authors: Gao Jie
Published: October 2021

China and Britain both found themselves in extremely precarious situations by the early summer of 1940, when Japan demanded that Britain close the Burma Road, a vital overland supply route for Chinese forces fighting against Japanese aggression. The British had just seen all of their continental European allies fall like dominoes to Hitler’s forces over the span of a few weeks, while China was fighting a losing defensive war against Japan with minimal outside support. China desperately needed to maintain its overland supply line to the British Empire, the Burma Road, but Britain feared that the very existence of this conduit of war materiel would provoke a Japanese attack on vulnerable British colonies in the Far East. American policy on Japanese aggression was ambiguous at this point and neither Britain nor China could realistically expect help from Washington in the short term. As a result, Britain signed a one-sided confidential memorandum to close the Burma Road to buy time and shore up its East Asian position to the extent that it was able. This deal, a lesser-studied counterpart to Prime Minister Neville Chamberlain’s appeasement policy in Europe, compromised the Chinese war effort against Japan, paved the way for the Japanese conquest of Southeast Asia, and ultimately failed to prevent Britain’s defeat in East Asia. Recognizing that this temporary concession would not moderate Japanese behavior, Britain reopened the Burma Road three months later. This paper examines the vital role of the Burma Road in the Chinese war effort in 1940 and why Japan demanded that London close it, then explores the factors that led to Britain’s unavoidable capitulation on the issue and subsequent reversal three months later, along with the consequences for the Allied war effort in the Far East.
Local Youth Policies between National Frameworks and Local Peculiarities: Examples from Two European Cities
Authors: Pohl Axel , Cuconato Morena
Published: October 2021

There are ongoing debates in youth research and politics about the impact of European and national youth policies on the local level. Based on the qualitative findings collected in the framework of the European Project partispace, this paper aims at analyzing whether and to what extent current local youth policies relates to national and European policies. Attempting to answer this question, it presents some empirical findings from a study on youth policies in two European cities: Bologna and Frankfurt. Before the reconstruction of the historically grown links between the local and the national youth policies, first the structures of current youth policies are analysed. After this, the results of expert interviews, focus groups with young people from a variety of youth scenes are presented to enlighten how youth policies work in these two urban contexts. It shows that they are linked to national policies in very different constellations with very different outcomes on the level of how they are perceived and taken up by the young people.
Le Deuxième Sexe/El segundo sexo in Mexico (1949–1980)
Authors: Moreno Esparza Hortensia , Buquet Corleto Ana Gabriela , Esparza Serra Luis Lorenzo
Published: October 2021

This article analyzes the reception of Le Deuxième Sexe in Mexico between 1949 and 1980, focusing on published references to the original French text and the first Spanish translation by Pablo Palant, El segundo sexo, published in Argentina in 1954. The authors consider publications by both conventional and feminist presses, centering their discussion on Rosario Castellanos, reader and commentator of the life and work of Beauvoir, and on the periodicals La Revuelta and fem.
Catalysing Parliamentary Action to Fight Climate Change
Authors: Clar Christoph
Published: October 2021

The report summarizes the Inter Pares conference on “Catalysing Parliamentary Action to Fight Climate Change”, which was held online on 11-12 May 2021, and identifies the main themes, issues and messages.
Two Replication Studies of the Relationships between Mathematical Knowledge for Teaching, Mathematical Quality of Instruction, and Student Achievement
Authors: Melhuish Kathleen , White Alexander , Sorto M. Alejandra , Thanheiser Eva
Published: October 2021

In this paper, we share two conceptual replications of Hill et al.’s (2012c) study linking Mathematical Knowledge for Teaching (MKT), Mathematical Quality of Instruction (MQI), and student assessment scores. In study 1, we share data from 4th and 5th grade teachers in an urban school district. In study 2, we share data from middle school teachers in a school district with a relatively high proportion of emergent bilingual students. By varying contexts, we found that Hill et al.’s (2012c) suggested use of the MKT cutoff points was not warranted in our differing settings. Further, we found some significant relationships between MKT, MQI, and student assessments; however, we were not able to reproduce these consistently with our data. We suggest that the relationship between teaching practice and MKT may be quite sensitive to contextual factors including grade level, demographics, school effects, and assessments. We recommend that policymakers and researchers take caution when using such instruments to evaluate program initiatives and identify teachers for remediation or leadership positions.

The impact sheet to this article can be accessed at 10.6084/m9.figshare.16610080.
Magical Amulets, Magical Thinking, and Semiotics in Early Byzantium
Authors: Tuerk-Stonberg Jacquelyn
Published: October 2021

The term ‘magic’ is problematic. Magic studies have rapidly developed in recent decades and have suggested various ways of understanding the term, especially regarding objects from the medieval Roman Empire, Byzantium. Two early Byzantine amulets (as case studies) display conventional semiotic structures, which include persuasive analogy, speech-acts, and show-acts. Persuasive analogy, speech-acts, and show-acts – and how they organize information – operate also in religious, medical, and philosophical examples. Accordingly, art, archaeology, and texts of ritual power exemplify intersecting communities of thought and various types of social practices. Magic studies is interdisciplinary, and it encourages critique of modern assumptions regarding authority and of our intellectual colonization of times past. This essay is broad with several object examples across media, written as a conference presentation. Another approach to these semiotic structures on magical amulets – with examination of fewer objects and wider attention to the historiography of magic studies – will appear in the forthcoming Oxford Handbook on Byzantine Art and Architecture, ed. Ellen Schwartz.
The Italian Theory of Comparative Law Goes Abroad
Authors: Grande Elisabetta , Núñez Rodrigo Míguez , Monateri Pier Giuseppe
Published: October 2021

The aim of this paper is to assess the influence of the Italian comparative law scholarship outside its national boundaries, and particularly in Latin America, where it has had its strongest impact. In order to achieve our goal we will start by sketching a picture of the current status of the Italian comparative law, tracing its roots, explaining its development and analyzing its weaknesses and strengths. After exploring its reception in South America, we will ultimately try to envisage the future challenges, directions and contributions of the Italian Theory – as we labeled the Italian comparative law “way”.
State Immunity and Serious Violations of Human Rights: Judgment No. 238 of 2014 of the Italian Constitutional Court Seven Years on
Authors: Focarelli Carlo
Published: October 2021

On 3 February 2021, the US Supreme Court affirmed the icj’s Jurisdictional Immunities of the State Judgment of 2012—according to which “a State is not deprived of immunity by reason of the fact that it is accused of serious violations of international human rights law”—adopting, thus, a position opposite to that taken by the Italian Corte Costituzionale in its well-known Judgment No. 238 of 2014. Based on a realist-constructivist theoretical approach to international law, this article argues that the only plausible legal perspective justifying Judgment No. 238 is a dynamic one. However, the Corte Costituzionale has substantially failed to argue the plausibility of the expected change in existing international law that it wished to promote for the future. To take its intended big leap realistically and successfully, the Italian position would have deserved a sounder theoretical analysis of international law and of the world system in which the latter is meant to work.
Soft Law in International Investment Law and Arbitration
Authors: Adinolfi Giovanna
Published: October 2021

In the more recent decades, international investment law (“iil”) and arbitration have been going through a process of recalibration prompted by both the intensification of cross-border capital flows and the States’ growing concerns over the potential restraints iil may impose upon the pursuit of public interests. The present contribution will pay attention to a specific feature that can be observed within these developments, i.e. the role played by soft law in investment arbitration and, more generally, under iil, also with a view to assessing the impact on the formation of binding international law of instruments formally devoid of normative force within the international legal order. After an introduction (Section 1), the contribution is articulated into four sections. Section 2 will first define the field of investigation. The case law of investment tribunals and the treaty practice under the more recent iia s will be then explored as to the reliance on soft law instruments for the purposes of settling procedural (Section 3) and substantive issues (Section 4). Some final remarks will close (Section 5).
Environmental Disasters and Humanitarian Protection: A Fertile Ground for Litigating Climate Change and Human Rights in Italy?
Authors: Vona Fabrizio
Published: October 2021

On 24 February 2021, the Italian Corte Suprema di Cassazione delivered a landmark ordinance unequivocally establishing that the existence of a situation of environmental degradation in the country of origin of an international protection seeker, which entails grave human rights violations, justifies the recognition of the humanitarian protection status. In ruling that the assessment of vulnerability, for the purpose of granting humanitarian protection, must also be conducted in relation to environmental and climatic conditions which are capable of seriously affecting the enjoyment of human rights, the Supreme Court potentially paves the way for a first wave of rights-based climate lawsuits before Italian civil courts.
Potential for the valorisation of brewer’s spent grains: A case study for the sequential extraction of saccharides and lignin
Authors: de Crane d’Heysselaer Simon , Bockstal Lauris , Jacquet Nicolas , Schmetz Quentin , Richel Aurore
Published: October 2021

This study highlights the possibility of using brewers’ grains (BSGs) for the successive extraction of the main lignocellulosic biopolymers, namely, cellulose, hemicelluloses and lignin. An exhaustive chemical characterisation revealed a variability of composition in distinct batches of BSGs, depending on their origin and the brewing process used. In particular, the protein content can vary from 13wt% to 23wt%, which is accompanied by a change in the hemicelluloses content from 9% to 23% (in the samples of our study). By applying a two-step aqueous treatment, involving an acid (1.25% v/v aq. H2SO4) and a base (3% w/v aq. NaOH) at a temperature of 120°C and fixed reaction time of a few tens of minutes (15–90 minutes), more than 80% of hemicelluloses could be recovered. Cellulose could be isolated at more than 68%, while a high purity lignin could be recovered from a lignin-rich fraction (70wt%). Our work also suggests that the variability of the chemical composition of these BSGs is a hindrance to achieving process standardisation and large-scale exploitation. The pooling of various materials is therefore not a recommended option, and the preliminary chemical analysis of the composition is therefore a prerequisite for an efficient extraction process.
Effect of frost on plants, leaves, and forecast of frost events using convolutional neural networks
Authors: Wassan Sobia , Xi Chen , Jhanjhi NZ , Binte-Imran Laiqa
Published: October 2021

Climate change brings many changes in a physical environment like plants and leaves. The flowers and plants get affected by natural climate and local weather extremes. However, the projected increase in the frost event causes sensitivity in plant reproduction and plant structure vegetation. The timing of growing and reproduction might be an essential tactic by which plant life can avoid frost. Flowers are more sensitive to hoarfrost than leaves but more sensitive to frost in most cases. In most cases, frost affects the size of the plant, its growth, and the production of seeds. In this article, we examined that how frost affects plants and flowers? How it affects the roots and prevents the growth of plants, vegetables, and fruits? Furthermore, we predicted how the frost will grow and how we should take early precautions to protect our crops? We presented the convolutional neural network model framework and used the conv1d algorithm to evaluate one-dimensional data for frost event prediction. Then, as part of our model contribution, we preprocessed the data set. The results were comparable to four weather stations in the United States. The results showed that our convolutional neural network model configuration is reliable.
Risk assessment of eight metals and their mixtures to aquatic biota in sediments with diffusive gradients in thin films (DGT): a case study in Pearl River intertidal zone
Authors: Gu Yang-Guang
Published: October 2021

Background

The ecotoxicological risk posed by metals and their mixtures in sediments depends on their bioavailability. Many methods for evaluating the bioavailability of metals in sediments/soils are time-consuming and expensive, and frequently result in equivocal outcomes. The diffusive gradients in thin films (DGT) technique is a good measure of bioavailability for metals that can avoid the above drawbacks. Therefore, more effective approaches to this method should be developed that focus on metal bioavailability. No studies have been conducted using DGT to assess metal mixtures to aquatic biota in sediments. This study is therefore the first attempt to assess sediment toxicity of metals and their mixtures to aquatic biota based on the DGT technique. The intertidal zone of the Pearl River Estuary is selected as a case study.

Results

The bioavailable (DGT-labile) concentrations of metals range as follows (μg/L): Cd, 0.34–3.62; Pb, 1.35–1.92; Ni, 0.67–92.83; Cu, 0.74–10.30; Zn, 28.60–296.94; Co, 0.03–58.85; Fe, 7.23–4539.36; and Mn, 19.40–6626.83. The risk quotient (RQ), which is the ratio between the measured metal concentrations in the environment (MEC) and the predicted no-effect concentration (PNEC), is conducted to evaluate the single metal risk. The RQ based on summing up the MEC/PNEC ratios (RQMEC/PNEC) and the RQ based on sum of toxic units (RQSTU) are used to assess risk of metal mixture. TheRQ values of Cd, Pb, Ni, Cu, Zn, Fe, and Mn significantly exceed 1, indicating that the adverse effects of the metals are not negligible. Regarding the toxicity of metal mixtures, the values of RQMEC/PNEC and RQSTU are both between 62.45 and 743.48, revealing that the possible risk has already occurred in the study area.

Conclusions

The two methods of RQMEC/PNEC and RQSTU based on DGT-labile metal concentrations are effective and suitable to estimate the toxicity of metal mixtures in sediments.
End-to-end learning for compound activity prediction based on binding pocket information
Authors: Tanebe Toshitaka , Ishida Takashi
Published: October 2021

Background

Recently, machine learning-based ligand activity prediction methods have been greatly improved. However, if known active compounds of a target protein are unavailable, the machine learning-based method cannot be applied. In such cases, docking simulation is generally applied because it only requires a tertiary structure of the target protein. However, the conformation search and the evaluation of binding energy of docking simulation are computationally heavy and thus docking simulation needs huge computational resources. Thus, if we can apply a machine learning-based activity prediction method for a novel target protein, such methods would be highly useful. Recently, Tsubaki et al. proposed an end-to-end learning method to predict the activity of compounds for novel target proteins. However, the prediction accuracy of the method was still insufficient because it only used amino acid sequence information of a protein as the input.

Results

In this research, we proposed an end-to-end learning-based compound activity prediction using structure information of a binding pocket of a target protein. The proposed method learns the important features by end-to-end learning using a graph neural network both for a compound structure and a protein binding pocket structure. As a result of the evaluation experiments, the proposed method has shown higher accuracy than an existing method using amino acid sequence information.

Conclusions

The proposed method achieved equivalent accuracy to docking simulation using AutoDock Vina with much shorter computing time. This indicated that a machine learning-based approach would be promising even for novel target proteins in activity prediction.
adabmDCA: adaptive Boltzmann machine learning for biological sequences
Authors: Muntoni Anna Paola , Pagnani Andrea , Weigt Martin , Zamponi Francesco
Published: October 2021

Background

Boltzmann machines are energy-based models that have been shown to provide an accurate statistical description of domains of evolutionary-related protein and RNA families. They are parametrized in terms of local biases accounting for residue conservation, and pairwise terms to model epistatic coevolution between residues. From the model parameters, it is possible to extract an accurate prediction of the three-dimensional contact map of the target domain. More recently, the accuracy of these models has been also assessed in terms of their ability in predicting mutational effects and generatingin silicofunctional sequences.

Results

Our adaptive implementation of Boltzmann machine learning, , can be generally applied to both protein and RNA families and accomplishes several learning set-ups, depending on the complexity of the input data and on the user requirements. The code is fully available athttps://github.com/anna-pa-m/adabmDCA. As an example, we have performed the learning of three Boltzmann machines modeling the Kunitz and Beta-lactamase2 protein domains and TPP-riboswitch RNA domain.

Conclusions

The models learned by are comparable to those obtained by state-of-the-art techniques for this task, in terms of the quality of the inferred contact map as well as of the synthetically generated sequences. In addition, the code implements both equilibrium and out-of-equilibrium learning, which allows for an accurate and lossless training when the equilibrium one is prohibitive in terms of computational time, and allows for pruning irrelevant parameters using an information-based criterion.
Transmission of multidrug-resistant tuberculosis in Shimen community in Shanghai, China: a molecular epidemiology study
Authors: Han Zhiying , Li Jing , Sun Guomei , Gu Kaikan , Zhang Yangyi , Yao Hui , Jiang Yuan
Published: October 2021

Background

Multidrug-resistant tuberculosis (MDR-TB) has become a major public health problem in China, with mounting evidence suggesting that recent transmission accounts for the majority of MDR-TB. Here we aimed to reveal the transmission pattern of an MDR-TB outbreak in the Jing'an District of Shanghai between 2010 and 2015.

Methods

We used whole-genome sequencing (WGS) to conduct genomic clustering analysis along with field epidemiological investigation to determine the transmission pattern and drug resistance profile of a cluster with ten MDR-TB patients in combining field epidemiological investigation.

Results

The ten MDR-TB patients with genotypically clustered Beijing lineage strains lived in a densely populated, old alley with direct or indirect contact history. The analysis of genomic data showed that the genetic distances of the ten strains (excluding drug-resistant mutations) were 0–20 single nucleotide polymorphisms (SNPs), with an average distance of 9 SNPs, suggesting that the ten MDR-TB patients were infected and developed the onset of illness by the recent transmission of M. tuberculosis. The genetic analysis confirmed definite epidemiological links between the clustered cases.

Conclusions

The integration of the genotyping tool in routine tuberculosis surveillance can play a substantial role in the detection of MDR-TB transmission events. The leverage of genomic analysis in combination with the epidemiological investigation could further elucidate transmission patterns. Whole-genome sequencing could be integrated into intensive case-finding strategies to identify missed cases of MDR-TB and strengthen efforts to interrupt transmission.
Dual Ureaplasma parvum arthritis: a case report of U. parvum septic arthritis following contralateral reactive arthritis in an immunosuppressed patient
Authors: Lemoine Lea , Le Brun Cecile , Maillot Francois , Thorey Camille , Boucaud Annaelle , Lemaignen Adrien , Bigot Adrien
Published: October 2021

Background

Ureaplasma parvum is usually part of the normal genital flora. Rarely can it cause invasive infections such as genitourinary infections, septic arthritis, or meningitis.

Case presentation

Here we present the first description of chronic ureterocystitis in a 56-year-old immunocompromised patient, complicated first by reactive arthritis and secondarily by contralateral septic arthritis due to U. parvum infection. U. parvum was detected in synovial fluid and in a urine sample. Treatment consisted of double-J stenting and targeted antibiotic therapy. Evolution showed resolution of urinary symptoms and clinical improvement of arthritis despite functional sequelae.

Conclusions

Given the high prevalence of U. parvum colonisation, this diagnosis should remain a diagnosis of exclusion. However, because of the difficulty in detecting this microorganism, it should be considered in unexplained subacute urethritis or arthritis, including reactive arthritis, especially in immunosuppressed patients. Real-time PCR positivity in the absence of a differential diagnosis should not be overlooked.
Xanthogranulomatous pyelonephritis infected with the Providencia stuartii: a case report and literature review
Authors: Xu Zhunan , Cai Tong , Zhang Xuebao , Wu Jitao , Liu Chu
Published: October 2021

Background

Xanthogranulomatous pyelonephritis (XGP) is a rare and severe chronic inflammatory disease of the renal parenchyma, which is most commonly associated with super-infections by bacteria such as E. coli, Proteus mirabilis, and occasionally Pseudomonas species.

Case presentation

Herein, we present a rare case of a patient with XGP infected with Providencia stuartii. Initially, the patient refused nephrectomy and underwent holmium laser lithotripsy and right ureteral stenting, followed by meropenem treatment of 7 days. Relapse occurred in the third month after discharge from the hospital, due to which she underwent a radical nephrectomy.

Discussion

The diagnosis of XGP is confirmed by histopathology. The standard treatment for XGP is antibiotic therapy and radical nephrectomy, but partial nephrectomy may be appropriate in select cases.
Hemichorea in a patient with ipsilateral cortical infarction: a case report
Authors: Wei Jie , Zhang Yue
Published: October 2021

Background

Hemichorea is usually caused by contralateral deep structures of brain. It rarely results from acute cortical ischemic stroke and that caused by ipsilateral brain lesions is even rarer.

Case presentation

A 64-year-old female presented with acute obtuseness and left-sided hemichorea. She had a history of right frontal lobe surgery and radiotherapy due to brain metastasis from lung cancer 8 years ago. MRI revealed acute left frontal lobe infarction in addition to an old right frontal lobe lesion. 18FDG PET-CT showed hypometabolism in the left frontal lobe and hypermetabolism in the right basal ganglia region and central sulcus. The choreatic movement remitted after antipsychotic treatment.

Conclusion

The mechanism of hemichorea after ipsilateral cortical infarction is poorly understood. We assume both previous contralateral brain lesion and recent ipsilateral ischemic stroke contributed to the strange manifestation in this case.
Cholinesterase inhibitor to prevent falls in Parkinson’s disease (CHIEF-PD) trial: a phase 3 randomised, double-blind placebo-controlled trial of rivastigmine to prevent falls in Parkinson’s disease
Authors: Neumann S. , Taylor J. , Bamford A. , Metcalfe C. , Gaunt D. M. , Whone A. , Steeds D. , Emmett S. R. , Hollingworth W. , Ben-Shlomo Y. , Henderson E. J.
Published: October 2021

Background

Falls are a common complication of Parkinson’s disease. There is a need for new therapeutic options to target this debilitating aspect of the disease. Cholinergic deficit has been shown to contribute to both gait and cognitive dysfunction seen in the condition. Potential benefits of using cholinesterase inhibitors were shown during a single centre phase 2 trial. The aim of this trial is to evaluate the effectiveness of a cholinesterase inhibitor on fall rate in people with idiopathic Parkinson’s disease.

Methods

This is a multi-centre, double-blind, randomised placebo-controlled trial in 600 people with idiopathic Parkinson’s disease (Hoehn and Yahr stages 1 to 4) with a history of a fall in the past year. Participants will be randomised to two groups, receiving either transdermal rivastigmine or identical placebo for 12 months. The primary outcome is the fall rate over 12 months follow-up. Secondary outcome measures, collected at baseline and 12 months either face-to-face or via remote video/telephone assessments, include gait and balance measures, neuropsychiatric indices, Parkinson’s motor and non-motor symptoms, quality of life and cost-effectiveness.

Discussion

This trial will establish whether cholinesterase inhibitor therapy is effective in preventing falls in Parkinson’s disease. If cost-effective, it will alter current management guidelines by offering a new therapeutic option in this high-risk population.

Trial registration

REC reference: 19/SW/0043.

EudraCT: 2018–003219-23.

ISCRTN:41639809(registered 16/04/2019).

ClinicalTrials.gov Identifier:NCT04226248

Protocol at time of publication

Version 7.0, 20th January 2021.
Second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab for patients with metastatic colorectal cancer
Authors: Yamamoto Shun , Nagashima Kengo , Kawakami Takeshi , Mitani Seiichiro , Komoda Masato , Tsuji Yasushi , Izawa Naoki , Kawakami Kentaro , Yamamoto Yoshiyuki , Makiyama Akitaka , Yamazaki Kentaro , Masuishi Toshiki , Esaki Taito , Nakajima Takako Eguchi , Okuda Hiroyuki , Moriwaki Toshikazu , Boku Narikazu
Published: October 2021

Background

The ML18174 study, which showed benefits of bevacizumab (BEV) continuation beyond progression (BBP) for metastatic colorectal cancer (mCRC), excluded patients with first-line progression-free survival (PFS) shorter than 3 months. The present study was conducted to evaluate the efficacy of second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab.

Methods

The subjects of this study were mCRC patients who experienced disease progression < 100 days from commencement of first-line chemotherapy containing BEV initiated between Apr 2007 and Dec 2016. Second-line chemotherapy regimens were classified into two groups with and without BEV/other anti-angiogenic agents (BBP and non-BBP) and efficacy and safety were compared using univariate and multivariate analysis.

Results

Sixty-one patients were identified as subjects of this study. Baseline characteristics were numerically different between BBP (n = 37) and non-BBP (n = 25) groups, such as performance status (0–1/> 2/unknown: 89/8/3 and 56/40/4%), RAS status (wild/mutant/unknown: 32/54/16 and 76/16/8%). Response rate was 8.6% in BBP group and 9.1% in non-BBP group (p = 1.00). Median PFS was 3.9 months in BBP group and 2.8 months in non-BBP group (HR [95%CI]: 0.79 [0.46–1.34], p = 0.373, adjusted HR: 0.87 [0.41–1.82], p = 0.707). Median overall survival was 8.5 months in BBP group and 5.4 months in non-BBP group (HR 0.66 [0.38–1.12], p = 0.125, adjusted HR 0.53 [0.27–1.07], p = 0.078).

Conclusion

In mCRC patients who experienced early progression in first-line chemotherapy, second-line chemotherapy showed poor clinical outcomes regardless use of anti-angiogenic agents.
Development and validation of genomic and epigenomic signatures associated with tumor immune microenvironment in hepatoblastoma
Authors: Zhang Yanbing , Zhang Tian , Yin Qiang , Luo Haiyan
Published: October 2021

Background

This study aimed to probe and verify aberrantly methylated and expressed genes in hepatoblastoma and to analyze their interactions with tumor immune microenvironment.

Methods

Aberrantly methylated and expressed genes were obtained by comprehensively analyzing gene expression and DNA methylation profiles from GSE81928, GSE75271 and GSE78732 datasets. Their biological functions were predicted by the STRING and Metascape databases. CIBERSORT was utilized for inferring the compositions of tumor-infiltrating immune cells (TIICs) in each sample. Correlation between hub genes and immune cells was then analyzed. Hub genes were validated in hepatoblastoma tissues via western blot or immunohistochemistry. After transfection with sh-NOTUM, migration and invasion of HuH-6 and HepG2 cells were investigated. The nude mouse tumorigenesis model was constructed.

Results

Totally, 83 aberrantly methylated and expressed genes were determined in hepatoblastoma, which were mainly involved in metabolic and cancer-related pathways. Moreover, their expression was liver-specific. 13 hub genes were screened, which were closely related to immune cells in hepatoblastoma tissues. Among them, it was confirmed that AXIN2, LAMB1 and NOTUM were up-regulated and SERPINC1 was down-regulated in hepatoblastoma than normal tissues. NOTUM knockdown distinctly weakened migration and invasion of HuH-6 and HepG2 cells and tumor growth in vivo.

Conclusions

This study identified aberrantly methylated and expressed signatures that were in relation to immune microenvironment in hepatoblastoma. Targeting NOTUM hub gene could suppress migration and invasion of hepatoblastoma cells. Thus, these aberrantly methylated and expressed genes might act as therapeutic agents in hepatoblastoma therapy.
Treatment outcomes of acute postoperative infectious endophthalmitis
Authors: Peng Kai-Ling , Kung Ya-Hsin , Tsai Hui-Shuang , Wu Tsung-Tien
Published: October 2021

Background

Acute postoperative endophthalmitis is one of the most severe complications of modern ophthalmic procedures including cataract surgeries, vitrectomy and intravitreal injection (IVI). We evaluated the treatment outcomes of acute postoperative infectious endophthalmitis.

Methods

In this retrospective study, we collected data from 82 patients with acute infectious endophthalmitis within 6 weeks after intraocular surgeries, including cataract surgeries, vitreoretinal surgeries, and IVI, from January 2010 to December 2019. We analyzed the pre-treatment, treatment-related and post-treatment factors that affected visual outcomes.

Results

The mean age was 67.65 ± 9.52 years, the proportion of male patients was 56.1%. The mean baseline vision was 1.92 (Snellen Equivalent SE], counting finger [CF]) ± 0.54 logarithm of the minimum angle of resolution (log MAR) and the mean final vision was 0.71 (SE, 39/200) ± 0.80 logMAR. Visual improvement was significant (P < 0.001). The pre-treatment factors affecting final visual outcomes were diabetes, hemodialysis, baseline vision, signs of vitreous opacity, and different surgeries before endophthalmitis; the treatment-related factors affecting visual outcomes were the choice factors between IVI of antibiotics alone and vitrectomy combined with IVI of antibiotics, and the injection numbers of antibiotics; post-treatment factors affecting visual outcomes were complications such as retinal detachment (RD), glaucoma and macular pucker. Furthermore, prior cataract surgery was associated with a better mean final vision of 0.57 (SE, 54/200) ± 0.67 logMAR while prior vitrectomy resulted in the worst mean final vision of 1.38 (SE, 21/500) ± 0.75 logMAR.

Conclusions

The important factors that affected the final visual prognosis, included diabetes, hemodialysis, baseline vision, severity of vitritis, treatment strategies and complications. The treatment outcomes revealed better final vision in prior cataract surgery than vitrectomy.
The effects of antifungal therapy on the recurrence of aspergillus infection after pulmonary aspergilloma resection: a study protocol for a single-center, prospective, non-blind, randomized, 24-month, parallel group study
Authors: Chen Xianqiu , Zhou Yiming , Zhang Lijuan , Xu Jinfu , Liang Shuo
Published: October 2021

Background

In recent years, the incidence of pulmonary aspergilloma has increased. The harm of aspergilloma is life-threatening massive hemoptysis, and the conventional treatment is surgical treatment. However, whether the antifungal treatment after surgery is required and the course of treatment before and after surgery are still unclear.

Methods

In this study, patients with pulmonary aspergilloma confirmed pathologically after surgery will be selected as subjects to conduct a single-center, randomized, parallel grouping, prospective, 2-year clinical study. Through regular visits, the recurrence of aspergillus infection, quality of life, lung function indicators, safety of antifungal therapy and other indicators were recorded to evaluate the recurrence risk of aspergillus infection and safety of antifungal agents. Cox proportional risk regression model was used to analyze the influencing factors of antifungal therapy on aspergillus infection recurrence after aspergillus bulbectomy. Cox multiple regression model was used for optimal model fitting, and regression coefficient (β), relative risk (RR) and 95% confidence interval of RR were calculated.

Discussion

The study will explore whether antifungal therapy could improve the quality of life, reduce the recurrence of aspergillus infection, and ultimately improve the prognosis of patients with aspergilloma. The study results will provide high-quality evidence-based medical evidence for the formulation, revision and optimization of international and domestic clinical guidelines and expert consensus on chronic aspergillus lung disease, effectively improve the clinical treatment effect of aspergilloma, and form the latest concept of diagnosis and treatment of aspergilloma.

Trial registration: The trial was registered on the Chinese Clinical Trial Registry website (https://www.chictr.org.cn/showprojen.aspx?proj=33231). Registration number: ChiCTR1800019990.
Assessment of the HScore as a predictor of disease outcome in patients with COVID-19
Authors: Bordbar Mohammadreza , Sanaei Dashti Anahita , Amanati Ali , Shorafa Eslam , Mansoori Yasaman , Dehghani Seyed Javad , Molavi Vardanjani Hossein
Published: October 2021

Severe coronavirus disease 2019 (COVID-19) accompanies hypercytokinemia, similar to secondary hemophagocytic lymphohistiocytosis (sHLH). We aimed to find if HScore could predict disease severity in COVID-19. HScore was calculated in hospitalized children and adult patients with a proven diagnosis of COVID-19. The need for intensive care unit (ICU), hospital length of stay (LOS), and in-hospital mortality were recorded. The median HScore was 43.0 (IQR 0.0–63.0), which was higher in those who needed ICU care (59.7, 95% CI 46.4–72.7) compared to those admitted to non-ICU medical wards (38.8, 95% CI 32.2–45.4; P = 0.003). It was also significantly higher in patients who died of COVID-19 (105.1, 95% CI 53.7–156.5) than individuals who survived (41.5, 95% CI 35.8–47.1; P = 0.005). Multivariable logistic regression analysis revealed that higher HScore was associated with a higher risk of ICU admission (adjusted OR = 4.93, 95% CI 1.5–16.17, P = 0.008). The risk of death increased by 20% for every ten units increase in HScore (adjusted OR 1.02, 95% CI 1.00–1.04, P = 0.009). Time to discharge was statistically longer in high HScore levels than low levels (HR = 0.41, 95% CI 0.24–0.69). HScore is much lower in patients with severe COVID-19 than sHLH. Higher HScore is associated with more ICU admission, more extended hospitalization, and a higher mortality rate. A modified HScore with a new cut-off seems more practical in predicting disease severity in patients with severe COVID-19.
Improvement of osteoporosis Care Organized by Nurses: ICON study - Protocol of a quasi-experimental study to assess the (cost)-effectiveness of combining a decision aid with motivational interviewing for improving medication persistence in patients with a recent fracture being treated at the fracture liaison service
Authors: Cornelissen Dennis , Boonen Annelies , Evers Silvia , van den Bergh Joop P. , Bours Sandrine , Wyers Caroline E. , van Kuijk Sander , van Oostwaard Marsha , van der Weijden Trudy , Hiligsmann Mickaël
Published: October 2021

Background

Given the health and economic burden of fractures related to osteoporosis, suboptimal adherence to medication and the increasing importance of shared-decision making, the Improvement of osteoporosis Care Organized by Nurses (ICON) study was designed to evaluate the effectiveness, cost-effectiveness and feasibility of a multi-component adherence intervention (MCAI) for patients with an indication for treatment with anti–osteoporosis medication, following assessment at the Fracture Liaison Service after a recent fracture. The MCAI involves two consultations at the FLS. During the first consultation, a decision aid is will be used to involve patients in the decision of whether to start anti-osteoporosis medication. During the follow-up visit, the nurse inquires about, and stimulates, medication adherence using motivational interviewing techniques.

Methods

A quasi-experimental trial to evaluate the (cost-) effectiveness and feasibility of an MCAI, consisting of a decision aid (DA) at the first visit, combined with nurse-led adherence support using motivational interviewing during the follow-up visit, in comparison with care as usual, in improving adherence to oral anti-osteoporosis medication for patients with a recent fracture two Dutch FLS. Medication persistence, defined as the proportion of patients who are persistent at one year assuming a refill gap < 30 days, is the primary outcome. Medication adherence, decision quality, subsequent fractures and mortality are the secondary outcomes. A lifetime cost-effectiveness analysis using a model-based economic evaluation and a process evaluation will also be conducted. A sample size of 248 patients is required to show an improvement in the primary outcome with 20%. Study follow-up is at 12 months, with measurements at baseline, after four months, and at 12 months.

Discussion

We expect that the ICON-study will show that the MCAI is a (cost-)effective intervention for improving persistence with anti-osteoporosis medication and that it is feasible for implementation at the FLS.

Trial registration

This trial has been registered in the Netherlands Trial Registry, part of the Dutch Cochrane Centre (Trial NL7236 (NTR7435)).

Version 1.0; 26-11-2020.
Role of radiofrequency ablation and cement injection for pain control in patients with spinal metastasis
Authors: Yildizhan Serhat , Boyaci Mehmet Gazi , Rakip Usame , Aslan Adem , Canbek Ihsan
Published: October 2021

Background

The study aimed to investigate the effects and reliability of simultaneous vertebroplasty and radiofrequency ablation or radiofrequency ablation applied alone for pain control in patients with painful spine metastasis, and to investigate the effect of preventing tumor spread in long-term follow-up.

Methods

Patients with painful vertebrae metastasis in the Afyonkarahisar Health Sciences University, Medical Faculty, Hospital Neurosurgery Clinic between 01.01.2015 and 01.06.2020 were recruited. They were divided into groups according to the surgical procedures applied. Group 1 included 26 patients who underwent radiofrequency ablation only, and group 2 included 40 patients who underwent vertebroplasty with radiofrequency ablation. Computed tomography and magnetic resonance imaging were performed in all patients pre-operation. The patients were followed for at least 6 months. Magnetic resonance imaging was performed at the end of the 6th month in neurologically stable patients. The metastatic lesion, pain, and quality of life were evaluated with Visual Analog Scale and Oswestry Disability Survey before and after the procedure.

Results

The mean VAS score before the procedure was 8.3 ± 1.07 in the RFA group, and a statistically significant difference was observed in VAS scores at all post-procedural measurement time-points (p < 0.001). The pain scores decreased at a rate of 58.8 and 69.6% of patients showed significant improvements in the QoL in the RFA-only group. The mean VAS score was 7.44 ± 1.06 in group RFA + VP before the procedure; the difference in the mean VAS scores was statistically significant at all measurement time-points after the procedure (p < 0.001). The mean pre-treatment Oswestry Index (to assess the QoL) was 78.50% in the RFA + VP group, which improved to 14.2% after treatment.

Conclusion

Ablation + vertebroplasty performed to control palliative pain and prevent tumor spread in patients with painful vertebral metastasis is more successful than vertebroplasty performed alone.