bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Fermentation in BCG Manufacture: Challenges and Ways Forward
Authors: Walker Kenneth Barry , Bacon Joanna
Published: March 2023

The BCG vaccine has been in existence for a century and has been instrumental in the control of tuberculosis. The method for producing the vaccine has not changed in a very long time and consists of pellicle growth followed by ball-milling, which is a lengthy and variable approach. There has been increasing interest in the possibility of producing the BCG vaccine by growing it in bioreactors, which could address some of the issues around variation between batches, increase yield, and circumvent the challenges associated with supply and demand. There is evidence that fermentation would be a quicker, more reproducible method of production, and would deliver BCG to a higher yield in a form that would be easier to characterise. However, a change to the manufacturing process may require new evidence of bioequivalence and may attract a requirement for preclinical studies as well as clinical trials from Phase I, through to efficacy studies. This chapter describes the history of the BCG vaccine and the issues of the current production method. We discuss the potential benefits of BCG fermentation and the regulatory steps required for such a method of production to be implemented.
Culture’s Divergence
Authors: Stephenson Janet
Published: March 2023

Culture is a difficult concept to apply to sustainability challenges because of its diverse interpretations. It has different uses in everyday language, different meanings depending on disciplines and their theoretical orientations, and different fundamental conceptualisations between Western and non-Western cultures. This chapter focuses on unpicking these divergences because unless they are visible and named, they will continue to handicap the effective use of culture as a framing for examining sustainability issues. Nine meanings of culture are identified. Each approach has an extraordinarily rich knowledge base which could contribute greatly to the work of the sustainability transition.
Culture’s Convergence
Authors: Stephenson Janet
Published: March 2023

This chapter takes an integrative approach to understanding culture. The starting position is that culture may have a coherent core of qualities, and that the divergent interpretations described in Chapter 2 may represent different perspectives on those common qualities. Drawing from definitions of culture sourced from all nine meanings, three frequently appearing qualities of culture are identified. These comprise ways of thinking, what people do and what people have or make. Most interpretations also see culture as being specific to a group of people, learned and passed on over time, with dynamic qualities and a tendency to endure over time. Although not all perspectives on culture reflect the totality of these qualities, all perspectives reflect at least some of them. The core elements and dynamics show promise for developing an analytic vocabulary and framework to support cultural analysis.
Optimization of Annealed Importance Sampling Hyperparameters
Authors: Goshtasbpour Shirin , Perez-Cruz Fernando
Published: March 2023

Annealed Importance Sampling (AIS) is a popular algorithm used to estimates the intractable marginal likelihood of deep generative models. Although AIS is guaranteed to provide unbiased estimate for any set of hyperparameters, the common implementations rely on simple heuristics such as the geometric average bridging distributions between initial and the target distribution which affect the estimation performance when the computation budget is limited. In order to reduce the number of sampling iterations, we present a parameteric AIS process with flexible intermediary distributions defined by a residual density with respect to the geometric mean path. Our method allows parameter sharing between annealing distributions, the use of fix linear schedule for discretization and amortization of hyperparameter selection in latent variable models. We assess the performance of Optimized-Path AIS for marginal likelihood estimation of deep generative models and compare it to compare it to more computationally intensive AIS.
Migrant Networks and Credit: Dynamics of Punjabi Migration to the Gulf Countries
Authors: Kaur Atinder Pal , Singh Ruchi
Published: March 2023

This chapter attempts to understand the role of networks in facilitating migration to Gulf countries from Punjab and the role of credit/debt to cover cost of migration. Theoretically, the study is based on an ethnographic and narrative approach. The ethnographic approach includes the nature of migration, place of migration, network relations, years of migration, and occupation of the migrants. The narrative approach is used to understand and analyze channels of migration and return migration. The paper will highlight the role of social networks in discovering Gulf nations with employment opportunities and various types of debt used to cover migration’s costs.
The Choice for the “Zendegie Normal (Normal Life)”: Changes Among Iranian Young Immigrants
Authors: Koo Gi Yeon
Published: March 2023

Up to a few years ago, reasons of Iranians’ migration and immigration were personal development, free life, better educational environment, and social welfare among others. However, the situation appears dire as it is circulated on social media that today’s Iranian youth migrate overseas for “air to breathe, basic living, and COVID-19 vaccination for survival”—it is their choice for a “normal life”. Iranian dream of breaking away from the day-to-day politics of surveillance and escaping to foreign countries are like virtual worlds in their reality. This chapter seeks to examine the Iranian’s forms of migration and the social context.
Reverse Orientalism? French Salafis’ Fascination with Saudi Arabia
Authors: Adraoui Mohamed-Ali
Published: March 2023

Recently, French Muslims have been seen by several media outlets and politicians to be increasingly influenced by some of the understandings of Islam that were born in Saudi Arabia. While some connections do undoubtedly exist, I show that what we are experiencing today has much more to do with a broad globalization of beliefs, symbols, and identities than with an explicit desire to make French Muslims embrace Salafism. More importantly, I show in this piece that the influence of some forms of Islam originating in the Gulf within French society can be first and foremost interpreted as the result of a desire to identify with a non-French way of being a Muslim. Analyzing the kind of relations between certain French Muslims and a country such as Saudi Arabia highlights the fascination for Salafism and the rejection of their home country’s values. Interestingly, as shown in this piece through specific examples, French Salafis are perpetuating an Orientalist view of the Islamic world, starting with Saudi Arabia, seen as a “the land of religious authenticity.” By essentializing identity, geography, and culture, this French Salafi Orientalist type represents an original way of looking and understanding “the Islamic East” today.
Economic Development Models of Doha and Dubai: A Comparative Analysis
Authors: Althani Aldana Jassim
Published: March 2023

This chapter explores the development models of Doha and Dubai by highlighting the economic, political, and social factors in Qatar and Dubai. This research examines the historical context of Dubai and Qatar and digs deeper to explore how each state adopted a certain development path, and then the role of leadership in promoting the development through states’ strategic visions. This chapter reports that profound political, economic, and social factors lead to different development strategies for Dubai and Doha.
Chai Karak: The Politics of Tea and the Coloniality of Appropriation in the UAE
Authors: Moaswes Abdulla
Published: March 2023

Chai karak is a popular tea beverage in in the UAE and the other Arab Gulf states that is widely consumed across class and ethnic lines, particularly among wealthy UAE citizens and the poorer South Asian manual labourers who make up a large proportion of the country’s population—also often thought of as the group that brought the beverage to the UAE. This study primarily aims to understand the effects of Emirati claims of ownership over chai karak in terms of its political and socioeconomic impact. It does this through an analysis of analogous case studies and a series of interviews with chai karak vendors in the UAE. This methodology explored the item’s position with regard to three main research areas: the relationships produced by claims of its ownership, their impact on the political and socioeconomic status of South Asians in the cafeteria industry, and what the ensuant contestations show about the UAE’s wider social relations. The study concludes that the discourse of ownership produced around chai karak resembles those produced as a result of colonial relationships. In this UAE, this creates a form of consent-based hegemony that acts alongside other mechanisms of maintaining the privilege of citizens of the country.
Social Justice in the Gulf States: A Case in Qatar
Authors: Rahaman Muhammad Mustafizur
Published: March 2023

Social justice continues to construct important agenda for discussion due to its role in addressing the problems of inequality and ensuring the rights of equality of employment and health. This chapter addresses social justice cases in Qatar by highlighting the new measures taken by Qatari Government in ensuring migrants’ rights and healthcare provisions during the COVID-19 pandemic. This chapter reports that Qatar has ensured a high form of social justice by vaccinating more than 99% of its residents. Qatar has also achieved some successes in promoting social justice through pioneering reforms in labor sector. Apart from visionary political leadership, robust judicial process, consolidation of social development institutions, and client-focused health policy and services have been instrumental in boosting up social justice.
Introduction
Authors: McCulloch Jock , Miller Pavla
Published: March 2023

This chapter draws parallels between the Marikana confrontation between police and striking platinum miners in 2012 and the longer history of mining in South Africa. Then as now, mining has been dangerous work performed mostly by migrant workers under the eye of brutal management and a violent state. For most of the twentieth century, South Africa’s gold mines were the most profitable sector of the national economy yet faced formidable challenges in containing costs, dealing with health crises and recruiting sufficient number of workers. It was in the context of the ongoing threat to their viability that the mining houses entered debates about the character and incidence of occupational lung disease, set up clinics and hospitals, employed medical staff, collected (or avoided collecting) statistics, negotiated with public officials, funded research, contracted with insurance companies, influenced the flow of information and helped shape the public perception of risk. The chapter places this dynamic in the context of current scholarly debates about the development of scientific knowledge. It then links post-apartheid political changes with the settlement, in 2019, of a massive class action by former gold miners for occupational injury. The chapter concludes by outlining the concept of manufactured ignorance. Precisely how such ignorance was made, contested and dismantled has informed the research and writing of this book.
Identifying Risk and Compensating Tuberculosis: 1916–1957
Authors: McCulloch Jock , Miller Pavla
Published: March 2023

Driven by concerns of the white Mine Workers Union, South Africa was the first state to compensate for silicosis and tuberculosis as occupational diseases. The Acts were woven around the binary pairing of miners (whites) and native labourers (blacks). That device enabled legislators to racialise the labour laws without mentioning race. This chapter traces the development of thorough medical examinations, comprehensive health care and a generous compensation system for whites, alongside a system designed to prevent the employment of men who already developed lung disease and to minimise compensation for the (black) majority of the workforce. Having reluctantly agreed to compensate tuberculosis, the Chamber of Mines was relentless in opposing the many critics who argued that the mines were a source of infection. As the critics reiterated, dust exposure created a pool of infected men who were repatriated to rural areas where little or no biomedical care was available. The low wages offered by the mines impoverished labour-sending communities, and this in turn created the ideal social setting for infection to take hold and to spread. Finally, because most infected miners did not receive compensation, their home communities were further impoverished by having to care for men who were no longer able to work.
The Research Community, Risk and Evidence: 1912–1932
Authors: McCulloch Jock , Miller Pavla
Published: March 2023

The closely knit research community, centred on the South African Institute of Medical Research and the Miners’ Phthisis Medical Bureau, was created by the gold mining industry and the state between 1912 and 1916. This chapter describes the establishment and day-to-day working of that research community. It then documents the accumulation of evidence on the risks associated with exposure to silica dust, the synergy between silicosis and tuberculosis, the spread of infection in the mine compounds, the problems arising from the repatriation of sick miners and the declining living standards and malnutrition in the labour-sending communities. Despite the evidence, the chapter concludes, the Chamber of Mines and its Chief Medical Officer strenuously maintained that the mines were safe.
Tuberculosis and Migrant Labour in the High Commission Territories: Basutoland and Swaziland: 1912–2005
Authors: McCulloch Jock , Miller Pavla
Published: March 2023

Basutoland came under British rule in the late nineteenth century. By the 1930s, the Territory’s transformation into a labour reserve for South Africa’s mines decimated its food production, impoverished its population and brought about a TB epidemic. The mines paid uneconomic wages and refused to pay compensation for occupational injury. In addition to those repatriated with tuberculosis or silicosis, the mines produced such a steady stream of sick and injured workers that mine accidents constituted the largest single cause of disability amongst men of working age.

Swaziland was the smallest of the three protectorates. Land alienation to white settlers under British concessions meant that by the early 1930s, the territory produced only a fifth of its food needs. As in the other HCTs, tax collection and occupational lung disease posed serious problems. However, commercial agriculture and large deposits of asbestos generated local employment and foreign exchange and made Swaziland less dependent on migrant wages.

In each of the HCTs, migrant workers faced even greater barriers in accessing compensation for occupational injury than black South Africans did. No circulars or instructions on the subject had been issued, miners were unaware of their rights, local officials did not understand the application process and travel to Johannesburg for medical examinations was not feasible for men who were dying. In all, the lack of medical capacity, the ongoing refusal to pay pensions to injured miners and the systematic failure to collect health statistics made the extent of the risk invisible. While the situation improved somewhat after independence, the mining industry continued to displace the burden of disability onto households and local communities.
Trends and Implications for the Educational Turn
Authors: Coleman Kathryn
Published: March 2023

The speculative idea that created this edited volume was a figuring exercise to build on connections, create new opportunities and generate new Scholarship of Learning and Teaching imaginaries for the future during the initial stages of the global pandemic. The project began by inviting interested colleagues at the Melbourne Graduate School of Education to participate in a think tank series as a thought experiment. Underpinned by a co-design process to reimagine educational opportunities in and for these precarious times through iterative ideation and prototyping to create connection and collaboration through co-creation. A speculative inquiry approach was chosen to direct the project because it is a relational and emergent “figuring” practice that builds from the shared propositions and ideas that seek to provoke and spark wonderings, concepts, and ideas that will be followed in each collaborative session that follows. This chapter will discuss how the research collaborations were fostered to result in the chapters presented and conclude with implications for the educational turn. The educational turn represents a shift of the Scholarship of Teaching and Learning from the peripheries of higher education to legitimate scholarly work within the academy that can inform and strengthen evidence-based approaches for impact on student learning in the future.
Approach of Electronic Structure Calculations to Crystal
Authors: Nakatani Naoki , Zheng Jia-Jia , Sakaki Shigeyoshi
Published: March 2023

Nowadays, the importance of molecular crystals and solids with regular structures is increasing in both basic chemistry and applied fields. However, theoretical studies of those systems based on electronic structure theories have been limited. Although density functional theory (DFT) calculations using generalized gradient approximation type functional under periodic boundary condition is effective for such theoretical studies, we need some improvements for calculating the dispersion interaction and the excited state of crystals. Accordingly, in this chapter, two methods for calculating the electronic structures of molecular crystals are discussed: cluster-model/periodic-model (CM/PM)-combined method and quantum mechanics/periodic-molecular mechanics (QM/periodic-MM) method. In the CM/PM-combined method, an infinite crystal system is calculated by the DFT method under periodic boundary condition, and important moieties, which are represented by CMs, are calculated by either DFT method with hybrid-type functionals or wave function theories such as the Møller–Plesset second-order perturbation theory (MP2), spin-component-scaled-MP2, and coupled-cluster singles and doubles theory with perturbative triples (CCSD(T)). This method is useful for gas adsorption into crystals such as metal–organic frameworks. In the QM/periodic-MM method, an important moiety is calculated using a QM method such as the DFT method with hybrid-type functionals and wave function theories, where the effects of the crystal are incorporated into the QM calculation via the periodic MM method using a classical force field. This method is useful for theoretical studies of excited states and chemical reactions. The applications of these methods in the following processes are described in this chapter: adsorption of gas molecules on metal–organic frameworks, chemical reactions in crystals, and luminescence of the crystals of transition metal complexes. To the best of our knowledge, the theoretical calculations conducted in this chapter show one of the successful approaches of electronic structure theories to molecular crystals, because of the reasonable and practical approximations.
Elastic and Plastic Soft Crystals with Superelasticity, Ferroelasticity, and Superplasticity
Authors: Takamizawa Satoshi , Kato Masako
Published: March 2023

Superelasticity is the ability of a plastically deformed solid to spontaneously recover its shape upon unloading due to stress loading. From its discovery in Au–Cd alloys in 1932, superelasticity had been believed to be limited to certain alloys until the discovery of “organic superelasticity” in 2014, which revealed it to be a general phenomenon observed in organic crystals along with ferroelasticity—reversible plastic deformability that is not accompanied by spontaneous shape recovery. In this chapter, we will introduce the discovery of organic superelasticity and the shape-memory effect, discuss superelasticity and ferroelasticity, and explain the properties and characteristics of various molecular crystals, including metal complexes. Furthermore, “organic superplasticity”—irreversible plastic deformation of several hundred percent or more, accompanied by the retention of crystallinity—has also been described.
Triboluminescence of Lanthanide Complexes
Authors: Hasegawa Miki , Hasegawa Yasuchika
Published: March 2023

The photoluminescence of lanthanide complexes originating from f–f transitions is generally sensitized through energy transfer from the ligand to the lanthanide ion in the excited state under UV irradiation. This phenomenon is known as the photo-antenna effect. Luminescence driven by mechanical stimuli, such as tapping or rubbing, is called mechanoluminescence or triboluminescence (TL). In recent years, reports on TL in rare-earth complexes, which have attracted attention as novel luminescent materials that do not require an electrical excitation source, have steadily increased. In this chapter, we focus on triboluminescent lanthanide complexes. Specifically, we introduce the history and detection methods of TL and cite recent examples of materials demonstrating this phenomenon, particularly coordination polymer-like and discrete molecular crystalline lanthanide complexes. Finally, we summarize the application prospects of these complexes as soft crystals.
Soft Crystal Chemiluminescence Systems Using Organic Peroxides
Authors: Hirano Takashi , Matsuhashi Chihiro
Published: March 2023

Chemiluminescence (CL) is a phenomenon in which a chemical reaction produces an excited-state product that emits light. Taking advantage of this property, several analytical methods to study the CL reactions by photon detection have been developed in the literature. By applying this methodology to molecular crystals, soft crystal CL systems have been constructed to analyze the intracrystalline reactions of chemiluminescent compounds. In this chapter, the fundamental concept and applications of CL are presented. Using the example of the CL reactions involving organic peroxides, important characteristics of CL such as chemiexcitation, quantum yield and emission wavelengths are discussed. Furthermore, CL in solid state and in molecular crystals are described. Finally, the application of organic peroxides as a soft crystal CL system and the characteristics of their intracrystalline reactions such as crystal structure-dependencies, reaction kinetics and inductions of phase transitions are elucidated. This chapter concludes with a brief outlook towards the future of soft crystal CL systems.
Boosting asymmetric charged DM via thermalization
Authors: Geller Michael , Heller-Algazi Zamir
Published: March 2023

Abstract

We consider a dark sector scenario with two dark matter species with opposite dark U(1) charges and an asymmetric population comprising some fraction of the dark matter abundance. A new mechanism for boosting dark matter is introduced, arising from the large mass hierarchy between the two particles. In the galaxy, the two species thermalize efficiently through dark Rutherford scattering greatly boosting the lighter dark matter particle, far above the virial and escape velocities in the galaxy, while the dark charge prevents it from escaping. We study the consequences of this scenario for direct-detection experiments, assuming a kinetic mixing between the dark photon and the photon. If the charged dark sector makes up 5% of the total DM mass in our galaxy and the mass ratio is between 103–104, we find that current and future experiments may probe the boosted light dark matter for masses down to 100 keV, in a hitherto unexplored parameter range.
Patient-related effects of primary nursing
Authors: Krüger Lars , Mannebach Thomas , Zittermann Armin , Wefer Franziska , von Dossow Vera , Rojas Hernandez Sebastian , Gummert Jan , Langer Gero
Published: March 2023

Background

Since January 2022, a primary nursing system called process-responsible nursing (PP) has substituted the standard room care system in an intensive care unit (ICU) at our institution. The process of the development and implementation of PP is already being evaluated in a separate study as an actual analysis prior to implementation, as well as after 6 and 12 months.

Aim

This pilot randomized controlled trial (RCT) aims to test the feasibility of an RCT. For this purpose, the duration of delirium, among other things, will be compared in the project ICU with the results of standard care in another ICU at the university hospital. As secondary aims, the incidence of delirium, anxiety, the satisfaction of relatives, and the effects of PP on nurses will be assessed.

Methods

It is planned to recruit about 400–500 patients over a period of one year. They will be allocated to PP or standard care. Delirium will be assessed using the Confusion Assessment Method for Intensive Care Units by specifically trained nurses three times a day. Anxiety in patients, the satisfaction of relatives, and the effects of PP on nurses will be evaluated using the numeric rating scale, a standardized questionnaire, and a focus group interview, respectively.

Expected results

The primary hypothesis is that compared to usual care PP reduces the duration of delirium by at least 8 h. Additional hypotheses are that PP reduces anxiety in patients and increases the satisfaction of relatives.
Field survey and molecular characterization of apicomplexan parasites in small mammals from military camps in Afghanistan
Authors: Schotte Ulrich , Binder Alfred , Goller Katja V. , Faulde Michael , Ruhl Silke , Sauer Sabine , Schlegel Mathias , Teifke Jens P. , Ulrich Rainer G. , Wylezich Claudia
Published: March 2023

Small mammals are an important reservoir for causative agents of numerous infectious diseases, including zoonotic and vector-borne diseases. The occurrence of these pathogens represents a regional but permanent threat for humans and animals in general and might especially weaken military personnel and companion animals in abroad missions. In our study, small mammals collected in military camps in Afghanistan (Feyzabad, Mazar-e Sharif, and Kunduz) were investigated for the presence of apicomplexans using histopathology and molecular methods. For this purpose, well-established and newly developed real-time PCR assays were applied. A high prevalence was detected not only in house mice (Mus musculus), but also in shrews (Crocidura cf. suaveolens) and grey dwarf hamsters (Cricetulus migratorius). The molecular characterization based on the 18S rRNA gene revealed a close relationship to a cluster of Hepatozoon sp. detected in voles of the genus Microtus. Hepatozoon canis DNA was detected in one house mouse as well as in two Rhipicephalus ticks from a dog puppy. In addition, around 5% of the house mice were found to be infected with far related adeleorinids showing the highest sequence identity of 91.5% to Klossiella equi, the only published Klossiella sequence at present. For their better phylogenetic characterization, we conducted metagenomics by sequencing of two selected samples. The resulting 18S rRNA gene sequences have a length of about 2400 base pairs including an insertion of about 500 base pairs and are 100% identical to each other. Histopathology together with organ tropism and detection rates verified this sequence as of Klossiella muris. In conclusion, we documented naturally occurring protozoan stages and the additional taxonomic characterization of a well-known commensal in mice by applying a combination of different approaches. The study is of medical, social, and biological importance for ensuring human and animal health in military camps and also stresses the required awareness for the potential risk of zoonoses.
Cinnamon (Cinnamomum cassia) hot water extract improves inflammation and tight junctions in the intestine in vitro and in vivo
Authors: Park Tae gwon , Kim Yu Rim , Park Soo-yeon , Choi Kwanyong , Kim Kyeong Jin , Kim Ji Yeon
Published: March 2023

The natural byproduct Cinnamomum cassia was widely used in ancient Asia to cure disease because of its various pharmacological effects. Despite its ethnomedicinal benefits, few studies on the intestinal anti-inflammatory effect of C. cassia have been reported. Therefore, this study aimed to evaluate the potential beneficial effects of C. cassia on the intestine in vitro and in vivo. Herein, the effects of cinnamon hot water extract (CWE) on tight junction (TJ) barrier function, transepithelial electrical resistance, and mRNA expression were confirmed in Caco-2 cells. The CWE treatment groups showed significantly enhanced cell permeability, proinflammatory cytokine mRNA expression, and TJ expression. CWE-treated mice showed an improved histological index and decreased cytokine concentrations compared with those of colitis model mice. These results suggest that CWE alleviated inflammatory damage and improved the TJ barrier, indicating that CWE may be used as a functional food to improve intestinal health.
Zebra finches (Taeniopygia guttata) demonstrate cognitive flexibility in using phonology and sequence of syllables in auditory discrimination
Authors: Ning Zhi-Yuan , Honing Henkjan , ten Cate Carel
Published: March 2023

Zebra finches rely mainly on syllable phonology rather than on syllable sequence when they discriminate between two songs. However, they can also learn to discriminate two strings containing the same set of syllables by their sequence. How learning about the phonological characteristics of syllables and their sequence relate to each other and to the composition of the stimuli is still an open question. We compared whether and how the zebra finches’ relative sensitivity for syllable phonology and syllable sequence depends on the differences between syllable strings. Two groups of zebra finches were trained in a Go-Left/Go-Right task to discriminate either between two strings in which each string contained a unique set of song syllables (‘Different-syllables group’) or two strings in which both strings contained the same set of syllables, but in a different sequential order (‘Same-syllables group’). We assessed to what extent the birds in the two experimental groups attend to the spectral characteristics and the sequence of the syllables by measuring the responses to test strings consisting of spectral modifications or sequence changes. Our results showed no difference in the number of trials needed to discriminate strings consisting of either different or identical sets of syllables. Both experimental groups attended to changes in spectral features in a similar way, but the group for which both training strings consisted of the same set of syllables responded more strongly to changes in sequence than the group for which the training strings consisted of different sets of syllables. This outcome suggests the presence of an additional learning process to learn about syllable sequence when learning about syllable phonology is not sufficient to discriminate two strings. Our study thus demonstrates that the relative importance of syllable phonology and sequence depends on how these features vary among stimuli. This indicates cognitive flexibility in the acoustic features that songbirds might use in their song recognition.
Value of peripheral blood circulating tumor cell detection in the diagnosis of thoracic diseases and the prediction of severity
Authors: Qi Chang , Xiong Xian-Zhi
Published: March 2023

Circulating tumor cell (CTC) detection, as a noninvasive liquid biopsy method, has been used in the diagnosis, prognostic indication, and monitoring of a variety of cancers. In this study, we aimed to investigate whether CTC detection could be used in the early diagnosis and prediction of severity of thoracic diseases. We enrolled 168 thoracic disease patients, all of whom underwent pathological biopsy. Carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) measurement was also performed in 146 patients. There were 131 cases of malignant thoracic diseases and 37 cases of benign lesions. We detected CTCs in a 5 ml peripheral blood sample with the CTCBiopsy® system and analyzed the value of CTC count for predicting disease severity. Of 131 patients with a diagnosis of thoracic malignancy, CTCs were found in blood samples from 122 patients. However, only 2 out of 37 patients with benign thoracic disease had no detectable CTCs. There was no significant correlation between CTC count and benign and malignant lesions (P = 0.986). However, among 131 patients who had been diagnosed with malignant lesions, 33 had lymph node metastasis or distant metastasis. The presence of CTCs was significantly correlated with metastasis (P = 0.016 OR = 1.14). The area under the receiver operating characteristic (ROC) curve was 0.625 (95% confidence interval (CI), 0.519 to 0.730 P = 0.032). In addition, with stage IA1 as the cutoff, all patients were further divided into an early-stage group and a late-stage group. CTC count was significantly correlated with disease progression (P = 0.031 OR = 1.11), with an area under the curve (AUC) of 0.599 (95% CI, 0.506–0.692 P = 0.47). The sensitivity and specificity of CTC detection for the diagnosis of disease stage were 72.3% and 45.5%, respectively. In addition, the cutoff of 2.5 CTCs was the same when predicting disease metastasis and staging. Furthermore, the combination of CTC count, demographic characteristics and tumor markers had better predictive significance for disease staging. CTC count can effectively indicate the stages and metastasis of thoracic diseases, but it cannot differentiate benign and malignant diseases.
A data-driven surrogate modeling approach for time-dependent incompressible Navier-Stokes equations with dynamic mode decomposition and manifold interpolation
Authors: Hess Martin W. , Quaini Annalisa , Rozza Gianluigi
Published: March 2023

This work introduces a novel approach for data-driven model reduction of time-dependent parametric partial differential equations. Using a multi-step procedure consisting of proper orthogonal decomposition, dynamic mode decomposition, and manifold interpolation, the proposed approach allows to accurately recover field solutions from a few large-scale simulations. Numerical experiments for the Rayleigh-Bénard cavity problem show the effectiveness of such multi-step procedure in two parametric regimes, i.e., medium and high Grashof number. The latter regime is particularly challenging as it nears the onset of turbulent and chaotic behavior. A major advantage of the proposed method in the context of time-periodic solutions is the ability to recover frequencies that are not present in the sampled data.
Design and preclinical evaluation of a novel apelin-based PET radiotracer targeting APJ receptor for molecular imaging of angiogenesis
Authors: Louis Béatrice , Nail Vincent , Nachar Oriane , Bouhlel Ahlem , Moyon Anaïs , Balasse Laure , Simoncini Stéphanie , Chabert Adrien , Fernandez Samantha , Brige Pauline , Hache Guillaume , Tintaru Aura , Morgat Clément , Dignat-George Françoise , Garrigue Philippe , Guillet Benjamin
Published: March 2023

APJ has been extensively described in the pathophysiology of angiogenesis and cell proliferation. The prognostic value of APJ overexpression in many diseases is now established. This study aimed to design a PET radiotracer that specifically binds to APJ. Apelin-F13A-NODAGA (AP747) was synthesized and radiolabeled with gallium-68 ([68Ga]Ga-AP747). Radiolabeling purity was excellent (> 95%) and stable up to 2 h. Affinity constant of [67Ga]Ga-AP747 was measured on APJ-overexpressing colon adenocarcinoma cells and was in nanomolar range. Specificity of [68Ga]Ga-AP747 for APJ was evaluated in vitro by autoradiography and in vivo by small animal PET/CT in both colon adenocarcinoma mouse model and Matrigel plug mouse model. Dynamic of [68Ga]Ga-AP747 PET/CT biodistributions was realized on healthy mice and pigs for two hours, and quantification of signal in organs showed a suitable pharmacokinetic profile for PET imaging, largely excreted by urinary route. Matrigel mice and hindlimb ischemic mice were submitted to a 21-day longitudinal follow-up with [68Ga]Ga-AP747 and [68Ga]Ga-RGD2 small animal PET/CT. [68Ga]Ga-AP747 PET signal in Matrigel was significantly more intense than that of [68Ga]Ga-RGD2. Revascularization of the ischemic hind limb was followed by LASER Doppler. In the hindlimb, [68Ga]Ga-AP747 PET signal was more than twice higher than that of [68Ga]Ga-RGD2 on day 7, and significantly superior over the 21-day follow-up. A significant, positive correlation was found between the [68Ga]Ga-AP747 PET signal on day 7 and late hindlimb perfusion on day 21. We developed a new PET radiotracer that specifically binds to APJ, [68Ga]Ga-AP747 that showed more efficient imaging properties than the most clinically advanced tracer of angiogenesis, [68Ga]Ga-RGD2.
A New Water-Based 87Sr/86Sr Isoscape Map of Central and NE Germany, with Special Emphasis on Mountainous Regions
Authors: Käßner A. , Kalapurakkal H. T. , Huber B. , Tichomirowa M.
Published: March 2023

In this study, we present a new 87Sr/86Sr isoscape map of Central and NE Germany. This area is characterized by an alternation of sedimentary basins and mountainous regions with a very variable lithology. Since lithology and rock age have a major impact on the isotopic composition of biologically available strontium, Central and NE Germany should reveal highly variable 87Sr/86Sr ratios. From lithological characteristics, particularly high ratios are expected in the mountainous regions of the Erzgebirge/Fichtelgebirge and the Harz Mountains. In contrast to these predictions, published 87Sr/86Sr isoscape maps of Central and NE Germany record rather uniform and low 87Sr/86Sr ratios. From this observation, we suspected that existing isoscape maps might be computed from an insufficient database, with mountainous regions being underrepresented. Our goal was to gather 87Sr/86Sr baselines for each major lithology of Central and NE Germany and to produce an accurate isoscape map of Central and NE Germany. In the first step, we evaluated the suitability of stream water and groundwater as a proxy for biologically available strontium. In a selected watershed, we present mixing relationships and a stream network model. We show that groundwater is prone to very local geologic and anthropogenic influences and should thus be avoided. Instead, we focussed our further sampling on stream water. Altogether, we used 119 new measurements of groundwater and stream water and a set of 23 auxiliary variables as a database for our new isoscape map of Central and NE Germany. Due to a sampling strategy that focussed on covering each major lithology, our measurements and the final isoscape map show a clear contrast between sedimentary basins and mountainous regions. For regions that have been sufficiently sampled, a direct comparison of the isoscape map with published and new data shows good agreement. Although Central and NE Germany were part of published isoscape maps, our new map is the first that predicts 87Sr/86Sr ratios in mountainous regions with high accuracy.
Effects of subpopulation extinction on effective size (Ne) of metapopulations
Authors: Kurland Sara , Ryman Nils , Hössjer Ola , Laikre Linda
Published: March 2023

Population extinction is ubiquitous in all taxa. Such extirpations can reduce intraspecific diversity, but the extent to which genetic diversity of surviving populations are affected remains largely unclear. A key concept in this context is the effective population size (Ne), which quantifies the rate at which genetic diversity within populations is lost. Ne was developed for single, isolated populations while many natural populations are instead connected to other populations via gene flow. Recent analytical approaches and software permit modelling of Ne of interconnected populations (metapopulations). Here, we apply such tools to investigate how extinction of subpopulations affects Ne of the metapopulation (NeMeta) and of separate surviving subpopulations (NeRx) under different rates and patterns of genetic exchange between subpopulations. We assess extinction effects before and at migration-drift equilibrium. We find that the effect of extinction on NeMeta increases with reduced connectivity, suggesting that stepping stone models of migration are more impacted than island-migration models when the same number of subpopulations are lost. Furthermore, in stepping stone models, after extinction and before a new equilibrium has been reached, NeRx can vary drastically among surviving subpopulations and depends on their initial spatial position relative to extinct ones. Our results demonstrate that extinctions can have far more complex effects on the retention of intraspecific diversity than typically recognized. Metapopulation dynamics need heightened consideration in sustainable management and conservation, e.g., in monitoring genetic diversity, and are relevant to a wide range of species in the ongoing extinction crisis.
A Randomized Controlled Trial of a Parenting Program to Improve Sibling Relationships
Authors: Pickering John A. , Crane Margaret E. , Hong Jinny , Nickel Ann-Kathrin , Chainey Carys , Sanders Matthew R.
Published: March 2023

Although parents of siblings play a crucial role in the development of both the positive and negative aspects of their children’s relationships, relatively few parenting programs specifically target sibling conflict alongside sibling warmth. To bridge this gap, the current study reports the outcomes of a randomized controlled trial evaluating a brief parenting intervention focusing on improving sibling relationships. A total of 74 parents reporting concerns about sibling conflict were randomized to either the Triple P brief discussion group intervention condition (n = 37) or the waitlist control condition (n = 37). Parents were predominately Caucasian, female, from a middle-income background. Parents completed a range of self-report measures examining the quality of the sibling relationship, parenting practices, family functioning, and child emotional and behavioral problems. Across treatment groups, participants showed improvements on almost all measures of sibling conflict, sibling warmth, child emotional and behavioral problems, parenting practices, and parenting confidence. Participants in the treatment group also experienced a greater reduction in the amount of help they wanted to manage sibling warmth, relative to participants in the control group. These results suggest that a low-intensity parenting intervention may only have a small effect on improving sibling relationships. Additional research is needed to determine how to broaden program efficacy for sibling conflict and parental adjustment, for families from diverse levels of income and family composition. Trial registration: ANZCTR 365567.
Comparing Self-Report Assessments and Scenario-Based Assessments of Systems Thinking Competence
Authors: Davis Kirsten A. , Grote Dustin , Mahmoudi Hesam , Perry Logan , Ghaffarzadegan Navid , Grohs Jacob , Hosseinichimeh Niyousha , Knight David B. , Triantis Konstantinos
Published: March 2023

Self-report assessments are used frequently in higher education to assess a variety of constructs, including attitudes, opinions, knowledge, and competence. Systems thinking is an example of one competence often measured using self-report assessments where individuals answer several questions about their perceptions of their own skills, habits, or daily decisions. In this study, we define systems thinking as the ability to see the world as a complex interconnected system where different parts can influence each other, and the interrelationships determine system outcomes. An alternative, less-common, assessment approach is to measure skills directly by providing a scenario about an unstructured problem and evaluating respondents’ judgment or analysis of the scenario (scenario-based assessment). This study explored the relationships between engineering students’ performance on self-report assessments and scenario-based assessments of systems thinking, finding that there were no significant relationships between the two assessment techniques. These results suggest that there may be limitations to using self-report assessments as a method to assess systems thinking and other competencies in educational research and evaluation, which could be addressed by incorporating alternative formats for assessing competence. Future work should explore these findings further and support the development of alternative assessment approaches.
Variance asymptotics for the area of planar cylinder processes generated by Brillinger-mixing point processes
Authors: Flimmel Daniela , Heinrich Lothar
Published: March 2023

We introduce cylinder processes in the plane defined as union sets of dilated straight lines (appearing as mutually overlapping infinitely long strips) generated by a stationary independently marked point process on the real line, where the marks describe the width and orientation of the individual cylinders. We study the behavior of the total area of the union of strips contained in a space-filling window ϱK as ϱ → ∞. In the case the unmarked point process is Brillinger mixing, we prove themean-square convergence of the area fraction of the cylinder process in ϱK. Under stronger versions of Brillinger mixing, we obtain the exact variance asymptotics of the area of the cylinder process in ϱK as ϱ → ∞. Due to the long-range dependence of the cylinder process, this variance increases asymptotically proportionally to ϱ3.
Updating Local Anisotropies with Template Matching During Geostatistical Seismic Inversion
Authors: Pereira Ângela , Azevedo Leonardo , Soares Amílcar
Published: March 2023

Iterative geostatistical seismic inversion methods are widely used to predict petro-elastic rock properties from seismic reflection data. When the model perturbation technique uses two-point geostatistics, these methods struggle to reproduce complex and nonstationary geological environments such as faults, folds and highly variable depositional systems. These limitations are often due to the use of a global variogram model to express the expected spatial continuity pattern of the property of interest. In complex geological environments a global variogram model might be unable to detect local heterogeneities and rapid variations of lithology, and result in nonrealistic geological models. Local heterogeneities might be predicted from the data using seismic attribute analysis, which can be imposed during geostatistical seismic inversion as local anisotropy models. In these approaches, the information about the local spatial continuity patterns is fixed and will guide and condition the entire inversion procedure, which can lead to errors and uncertainty in areas where this approach is not appropriate due to high local uncertainty of geological features, given the poor signal-to-noise ratio of the data or the presence of important geological features below the seismic resolution. This work proposes an iterative geostatistical seismic inversion method which iteratively updates the local spatial continuity models based on the trace-by-trace misfit between observed and predicted seismic data. The update of the local spatial continuity models aims at surpassing the limitations of the seismic inversion methods that use a fixed a priori variogram model. The method is successfully illustrated in a challenging two-dimensional synthetic data set and in a real case application. The results demonstrate the benefit of updating iteratively the imposed local spatial continuity patterns based on the data misfit. The inverted models are capable of better predicting the location of faults and reproducing the continuity of sinuous channels.