bluuebunny/crossref_metadata_2025 huggingface dataset:
Are mGluR2/3 Inhibitors Potential Compounds for Novel Antidepressants?
Authors: Jiang Yajie , Zou Manshu , Ren Tingting , Wang Yuhong
Published: November 2022

Depression is the most common mental illness characterized by anhedonia, avolition and loss of appetite and motivation. The majority of conventional antidepressants are monoaminergic system selective inhibitors, yet the efficacies are not sufficient. Up to 30% of depressed patients are resistant to treatment with available antidepressants, underscoring the urgent need for development of novel therapeutics to meet clinical needs. Recent years, compounds acting on the glutamate system have attracted wide attention because of their strong, rapid and sustained antidepressant effects. Among them, selective inhibitors of metabotropic glutamate receptors 2 and 3 (mGluR2/3) have shown robust antidepressant benefits with fewer side-effects in both preclinical and clinical studies. Thus, we here attempt to summarize the antidepressant effects and underlying mechanisms of these inhibitors revealed in recent years as well as analyze the potential value of mGluR2/3 selective inhibitors in the treatment of depression.
The organization of the human organ trade: a comparative crime script analysis
Authors: Ambagtsheer Frederike , Bugter Roos
Published: November 2022

This study fills critical knowledge gaps into the organization of organ trade utilizing crime script analysis. Adopting a situational crime prevention approach, this article draws from law enforcement data to compare the crime commission process (activities, cast and locations) of 2 prosecuted organ trade cases: the Medicus case and the Netcare case. Both cases involved transnational criminal networks that performed kidney transplants from living donors. We further present similarities and differences between illegal and legal living donor kidney transplants that may help guide identification and disruption of illegal transplants. Our analysis reveal the similar crime trajectories of both criminal cases, in particular the extensive preparations and high degree of organization that were needed to execute the illegal transplants. Offenders in the illegal transplant schemes utilized the same opportunity structures that facilitate legal transplants, such as transplant units, hospitals and blood banks. Our results indicate that the trade is embedded within the transplant industry and intersects with the transport- and hospitality sector. The transplant industry in the studied cases was particularly found to provide the medical infrastructure needed to facilitate and sustain organ trade. When compared to legal transplants, the studied illegal transplant scripts reveal a wider diversity in recruitment tactics and concealment strategies and a higher diversity in locations for the pre-operative work-up of donors and recipients. The results suggest the need for a broader conceptualization of the organ trade that incorporates both organized crime and white collar crime perspectives.
Role of female teachers of childhood education in directing children towards effective use of smart devices
Authors: Al-Barakat Ali Ahmad , Al-Hassan Omayya M. , AlAli Rommel Mahmoud , Al-Hassan Mu’aweya Mohammad , Al sharief Ramzia Ali
Published: November 2022

This study endeavors to investigate the role of female teachers of childhood education in directing children towards the effective use of smart devices in developing their learning experiences. The sample of the study consisted of 83 female teachers in the northern region of Jordan, who were selected using the available sampling method. To achieve the aim of the study, a semi-structured interview was prepared and its validity and consistency were verified.

The results shown that childhood education female teachers achieved advanced roles in directing children towards the effective use of smart devices, where effective direction towards the use of smart devices was represented in: directing children to self-organize their learning during using smart devices, directing children to acquire digital social interaction skills and directing them to learn innovation during using smart devices, with the importance of directing them to avoid the harms of using smart devices through preventive guidance.

Moreover, the findings of the study revealed the importance of directing children to participate in various digital activities, as well as directing them to learn through digital applications that are purposeful and suitable to their mental capabilities. Based on the research findings, the study presented a number of relevant recommendations.
A typology for digital leadership in higher education: the case of a large-scale mobile technology initiative (using tablets)
Authors: Ghamrawi Norma , M. Tamim Rana
Published: November 2022

This study investigated a digital reform initiative, rated excellent by the government, of one higher education institution (HEI) in an Arab State in the Gulf. The focus of the study was to develop a digital typology, while exploring the leadership attributes that characterized the core leadership team, as they accomplished the migration towards a digital culture in one year, within a context where faculty members showed resistance against digitalization. The study was conducted immediately after the implementation of the initiative that took place over the course of one year, just before the Covid-19 pandemic. Semi-structured interviews were conducted with all the six key individuals in the leadership team who led this initiative. Data was analyzed using content-based analysis. Findings of the study were used to synthesize a 5D typology for digital leadership attributes: (1) Digital competence; (2) Digital culture; (3) Digital Differentiation; (4) Digital governance; and (5) Digital advocacy. The paper provides in depth discussion how these attributes supported the adaptive ability of a Higher Education Institution towards accepting digitalization.
Jellyfish blooms challenge the provisioning of ecosystem services in the Korean coastal waters
Authors: Lee Sun-Hee , Scotti Marco , Jung Sukgeun , Hwang Jiang-Shiou , Molinero Juan Carlos
Published: November 2022

Temperate fisheries grounds are exposed to compound effects of jellyfish proliferations and fishing pressure, which affect local fisheries, cause economic losses, and threaten seafood supply. Here, we quantify the interlink between climate variability and jellyfish blooms and their impact on the Japanese anchovy (Engraulis japonicus), in the Korean coastal waters. We used a bioclimate dataset (2010–2019) that includes quantitative information of two major bloom-former species, Aurelia coerulea and Nemopilema nomurai, in the Korean Peninsula. We show that climate phenomena governing East Asia regions explain circa half of jellyfish variability. In turn, jellyfish blooms have a significant negative effect on anchovy interannual changes (r = -0.47, P < 0.01), which varies along with the bloom magnitude. Our results indicate that the intensity of jellyfish blooms, more than their duration, has a predominant effect on anchovy and coastal fisheries production. We also suggest the possibility of using climate signals for assessing and eventually predicting, interannual abundance changes of jellyfish in the Korean Peninsula. These results stress the challenge posed by jellyfish blooms to the provisioning of ecosystem services via their influence on marine harvested fish and further highlight the need for their integration into ecosystem-based management.
Organic litter dynamics in headwater streams draining contrasting land uses
Authors: Pye Marian C. , Vaughan Ian P. , Ormerod Steve J. , Durance Isabelle
Published: November 2022

Climate change could alter fluxes of organic matter and macronutrients through freshwater ecosystems potentially affecting stream organisms. However, riparian controls on litter dynamics offer an opportunity to adapt headwaters to climate change by protecting or restoring riparian vegetation. We assessed how riparian land cover and climatic variability affected the supply, retention and downstream transport of particulate organic matter (POM) in headwaters—the most extensive small water bodies in temperate landscapes. Leaf litter inputs, benthic stocks and suspended organic matter were measured nominally monthly in second–third-order streams draining broadleaf woodland, conifer, acid moorland and circumneutral moorland over four years with varying discharge. Streams draining broadleaf woodland received more leaf litter from the riparian zone than conifer and moorland and transported higher concentrations of CPOM and FPOM at base flows. Broadleaf sites had higher CPOM stocks, even after hydrological events that reduced CPOM in conifer and moorland sites. In contrast, FPOM dynamics reflected hydrological conditions irrespective of land cover. These results show how some organic matter fractions in streams are sensitive to hydrological conditions, illustrating how wetter climates will influence FPOM exports. Nevertheless, riparian broadleaves have the potential to offset climatic effects on organic matter processing in headwaters through the replenishment and retention of CPOM.
On Nontrivial Weak Dicomplementations and the Lattice Congruences that Preserve Them
Authors: Kwuida Leonard , Mureşan Claudia
Published: November 2022

We study the existence of nontrivial and of representable (dual) weak complementations, along with the lattice congruences that preserve them, in different constructions of bounded lattices, then use this study to determine the finite (dual) weakly complemented lattices with the largest numbers of congruences, along with the structures of their congruence lattices. It turns out that, if $$n\ge 7$$

n
≥
7

is a natural number, then the four largest numbers of congruences of the n–element (dual) weakly complemented lattices are: $$2^{n-2}+1$$

2

n
-
2

+
1

, $$2^{n-3}+1$$

2

n
-
3

+
1

, $$5\cdot 2^{n-6}+1$$

5
·

2

n
-
6

+
1

and $$2^{n-4}+1$$

2

n
-
4

+
1

, which yields the fact that, for any $$n\ge 5$$

n
≥
5

, the largest and second largest numbers of congruences of the n–element weakly dicomplemented lattices are $$2^{n-3}+1$$

2

n
-
3

+
1

and $$2^{n-4}+1$$

2

n
-
4

+
1

. For smaller numbers of elements, several intermediate numbers of congruences appear between the elements of these sequences.
Plant strategies to mine iron from alkaline substrates
Authors: Vélez-Bermúdez Isabel Cristina , Schmidt Wolfgang
Published: November 2022

In concert with oxygen, soil alkalinity strongly restricts the availability of iron, an essential nutrient with a multitude of functions in living organisms. In addition to its role in mitochondrial energy metabolism and as a cofactor for enzymes, in plants iron also plays key roles in photosynthesis and is required for chlorophyll biosynthesis. The ability to thrive in calcareous soils, referred to as calcicole behaviour, is the readout of an amalgam of traits of which efficient foraging of iron is a decisive factor. Recently, the well-established concept of two distinct iron uptake strategies, phylogenetically separating grasses from other land plants, was expanded by the discovery of auxiliary mechanisms that extend the range of edaphic conditions to which a species can adapt. Secretion of a tailor-made cocktail of iron-mobilising metabolites into the rhizosphere, the composition of which is responsive to a suite of edaphic and internal cues, allows survival in calcareous soils through a competitive iron acquisition strategy, which includes intricate interactions with the consortium of associated microorganisms in, on, and around the roots. This versatile, reciprocal plant-microbiome interplay affects iron mobilisation directly, but also collaterally by impacting growth, fitness, and health of the host. Here, we review the mechanisms and the multifaceted regulation of iron acquisition in plants, taking into consideration the specific constraints associated with the uptake of iron from alkaline soils. Knowledge on how plants extract iron from such soils sets the stage for a better understanding of essential ecological processes and for combatting iron malnutrition in humans.
Maternal Employment Shapes Daughters’ Employment Stability in Egypt: Evidence for the Intergenerational Transmission of Labor Force Attachment
Authors: Abouelenin Mariam , Hu Yang
Published: November 2022

Research has documented how maternal employment influences daughters’ participation in paid employment. However, we know far less about how maternal employment during daughters’ adolescence relates to the daughters’ subsequent employment stability. Analyzing data from three waves (2006, 2012, and 2018) of the Egypt Labor Market Panel Survey (N = 3,345) using structural equation models, this study compares the employment stability of women with and without working mothers during adolescence and examines how the influence of maternal employment on daughters’ employment stability varies with employment sector. Furthermore, a decomposition method is applied to determine the extent to which daughters’ education mediates the association between maternal employment and their employment stability. The results show that mothers’ employment is positively associated with their adult daughters’ employment stability. This intergenerational association is sector specific: mothers’ employment in a given sector only bolsters their daughters’ employment stability in the same sector. The daughter’s education mediates only a small portion of the intergenerational association in the public sector. The findings highlight the important role of Egypt’s institutional settings in configuring the intergenerational transmission of employment stability among women, and suggest that policies that support working mothers have the potential to bolster their daughters’ long-term labor market attachment.
A hybrid CUDA, OpenMP, and MPI parallel TCA-based domain adaptation for classification of very high-resolution remote sensing images
Authors: Garea Alberto S. , Heras Dora B. , Argüello Francisco , Demir Begüm
Published: November 2022

Domain Adaptation (DA) is a technique that aims at extracting information from a labeled remote sensing image to allow classifying a different image obtained by the same sensor but at a different geographical location. This is a very complex problem from the computational point of view, specially due to the very high-resolution of multispectral images. TCANet is a deep learning neural network for DA classification problems that has been proven as very accurate for solving them. TCANet consists of several stages based on the application of convolutional filters obtained through Transfer Component Analysis (TCA) computed over the input images. It does not require backpropagation training, in contrast to the usual CNN-based networks, as the convolutional filters are directly computed based on the TCA transform applied over the training samples. In this paper, a hybrid parallel TCA-based domain adaptation technique for solving the classification of very high-resolution multispectral images is presented. It is designed for efficient execution on a multi-node computer by using Message Passing Interface (MPI), exploiting the available Graphical Processing Units (GPUs), and making efficient use of each multicore node by using Open Multi-Processing (OpenMP). As a result, an accurate DA technique from the point of view of classification and with high speedup values over the sequential version is obtained, increasing the applicability of the technique to real problems.
An Investigation of the Impact and Resilience of British High Streets Following the COVID-19 Lockdown Restrictions
Authors: Hill Abigail , Cheshire James
Published: November 2022

British high streets have faced significant economic and cultural challenges as a consequence of the COVID-19 pandemic. This is predominantly due to government enforced restrictions which required all ‘non-essential’ retail to close, resulting in a significant change in the way consumers interacted with high streets. While all premises related to the retail or hospitality sector were forced to close, leading to rising vacancy rates, some high streets were more resilient to the economic shock than others. In this paper we detect some of the unforeseen consequences of the pandemic on British high streets and create a measure of resilience. The impact of the lockdown restrictions have resulted in some high streets, notably Spring Street in Paddington, London, experiencing disproportionate decline. Others including Northolt Road in Harrow, London were able maintain their occupancy. This study provides a typology of high street resilience incorporating the impact of the COVID-19 lockdown restrictions and links the impact of government policy to the economic performance of high streets. The outcomes from this research address both local and national policy contexts as the resilience typology has the potential to assist in funding allocation for recovery and regeneration projects.
Machine learning predicting and engineering the yield, N content, and specific surface area of biochar derived from pyrolysis of biomass
Authors: Leng Lijian , Yang Lihong , Lei Xinni , Zhang Weijin , Ai Zejian , Yang Zequn , Zhan Hao , Yang Jianping , Yuan Xingzhong , Peng Haoyi , Li Hailong
Published: November 2022

Biochar produced from pyrolysis of biomass has been developed as a platform carbonaceous material that can be used in various applications. The specific surface area (SSA) and functionalities such as N-containing functional groups of biochar are the most significant properties determining the application performance of biochar as a carbon material in various areas, such as removal of pollutants, adsorption of CO2and H2, catalysis, and energy storage. Producing biochar with preferable SSA and N functional groups is among the frontiers to engineer biochar materials. This study attempted to build machine learning models to predict and optimize specific surface area of biochar (SSA-char), N content of biochar (N-char), and yield of biochar (Yield-char) individually or simultaneously, by using elemental, proximate, and biochemical compositions of biomass and pyrolysis conditions as input variables. The predictions of Yield-char, N-char, and SSA-char were compared by using random forest (RF) and gradient boosting regression (GBR) models. GBR outperformed RF for most predictions. When input parameters included elemental and proximate compositions as well as pyrolysis conditions, the test R2values for the single-target and multi-target GBR models were 0.90–0.95 except  for  the two-target prediction of Yield-char and SSA-char which had a test R2of 0.84 and the three-target prediction model which had a test R2of 0.81. As indicated by the Pearson correlation coefficient between variables and the feature importance of these GBR models, the top influencing factors toward predicting three targets were specified as follows: pyrolysis temperature, residence time, and fixed carbon for Yield-char; N and ash for N-char; ash and pyrolysis temperature for SSA-char. The effects of these parameters on three targets were different, but the trade-offs of these three were balanced during multi-target ML prediction and optimization. The optimum solutions were then experimentally verified, which opens a new way for designing smart biochar with target properties and oriented application potential.

Graphical Abstract
Understanding internal migration in the UK before and during the COVID-19 pandemic using twitter data
Authors: Wang Yikang , Zhong Chen , Gao Qili , Cabrera-Arnau Carmen
Published: November 2022

The COVID-19 pandemic has greatly affected internal migration patterns and may last beyond the pandemic. It raises the need to monitor the migration in an economical, effective and timely way. Benefitting from the advancement of geolocation data collection techniques, we used near real-time and fine-grained Twitter data to monitor migration patterns during the COVID-19 pandemic, dated from January 2019 to December 2021. Based on geocoding and estimating home locations, we proposed five indices depicting migration patterns, which are demonstrated by applying an empirical study at national and local authority scales to the UK. Our findings point to complex social processes unfolding differently over space and time. In particular, the pandemic and lockdown policies significantly reduced the rate of migration. Furthermore, we found a trend of people moving out of large cities to the nearby rural areas, and also conjunctive cities if there is one, before and during the peak of the pandemic. The trend of moving to rural areas became more significant in 2020 and most people who moved out had not returned by the end of 2021, although large cities recovered more quickly than other regions. Our results of monthly migration matrixes are validated to be consistent with official migration flow data released by the Office for National Statistics, but have finer temporal granularity and can be updated more frequently. This study demonstrates that Twitter data is highly valuable for migration trend analysis despite the biases in population representation.
Cartel Regulation
Authors: Dasgupta Lovely
Published: November 2022

Cartels are the anti-thesis to the objectives pursued by competition law regimes world over. The objective of competition law is to protect the process of competition and maximization of consumer welfare by forcing producers to offer consumers a greater choice of high-quality products and services at low prices. Cartels, on the other hand, are cooperative arrangements between competitors to raise prices and reduce choices to the disadvantage of consumers, as well as to curtail the incentive of innovation and quality. In the Indian context, cartels present a graver problem as they not only threaten to end consumers’ choices but also over-ride the bargaining power of small and medium enterprises as well as small traders. Cartels in a developing country like India thus exploit the lack of bargaining power of all the groups in a relatively weaker bargaining position.
Unfolding macroprudential mechanisms: central bank-led mechanisms during the post-Global Financial Crisis Turkish experience
Authors: Akgünay Sinan
Published: November 2022

The Global Financial Crisis of 2008 was followed by an increased volatility in capital flows, posing considerable macro-financial risks, especially for emerging markets. Turkey addressed these macro-financial risks between 2010 and 2011. Principal decision makers at the Central Bank of the Republic of Turkey took policy actions by introducing policy mixes that trigger causal mechanisms informing the behaviour of bankers and their customers at the macro level to contain such risks. Utilising insights from causal mechanisms theory, critical realism, and realist evaluation, this article explores how the Central Bank implemented the policy mix. Our central argument is that at the macro level (i.e., structural and institutional contexts), causal mechanisms link actions with micro-level contexts (i.e., perceptions and reasoning of the target audience), whilst at the micro level, multiple causal mechanisms link policy outcomes with actor behaviour through non-linear feedback mechanisms. Our article contributes to the causal mechanisms literature by linking policy mixes and policy outcomes via causal mechanisms that informed agential actions and outcomes containing macro-financial risks.
Peltigera (Lecanoromycetes) on Mt Kilimanjaro, East Africa
Authors: Kaasalainen Ulla , Biermann Lea , Mollel Neduvoto P. , Schmidt Alexander R. , Hemp Andreas
Published: November 2022

Tropical mountain forests are hotspots of biodiversity that are widely threatened by human population pressure and climate change. However, the cryptogamic species richness of many tropical mountain regions is insufficiently known, the poorly understood biodiversity of tropical African lichens being a prime example. To study the diversity of the genus Peltigera (Ascomycota, Lecanoromycetes) in East Africa, we studied lichens in a wide range of habitats on the slopes of Mt Kilimanjaro in Tanzania. Ranging from savannah to alpine heath vegetation and from natural forests to agricultural environments, 13 habitat types were sampled for lichens, which were then identified based on the nuITS genetic marker and morphology. We found eight Peltigera species on the slopes of Mt Kilimanjaro, including P. alkalicola sp. nov., P. dolichorhiza, P. polydactyloides, P. praetextata, P. rufescentiformis, P. seneca, P. sorediifera and P. ulcerata. Peltigera is most common and species-rich in the subalpine Erica forest zone, and four of the eight detected species were present only in the subalpine and alpine vegetation zones. Peltigera alkalicola was identified as a previously undescribed species, growing on trachybasaltic lava in the subalpine and alpine zones of Mt Kilimanjaro. The species resembles P. lepidophora but differs by possessing smaller thalli and peltate isidia that are distinctly dark on the lighter, tomentose lamina. Based on data from the NCBI GenBank, P. alkalicola probably also occurs in Alaska (USA) and Ningxia (China). This suggests that even though the species might generally be rare, it may have a global distribution in extreme mountain environments. For the first time, we report P. sorediifera from Tanzania and P. seneca from Africa.
A terrifying poison or a cheap fertilizer? The life and death of Mount Vesuvius ash
Authors: Guerra Corinna
Published: November 2022

Argument

During the eighteenth century, chemists in the Kingdom of Naples (the South of Italy) were very busy analyzing the chemical composition of ash from Mount Vesuvius. Undoubtedly, after a huge eruption this dusty phenomenon was the most important scientific object of debate. In fact, it was crucial to determine if there were dangerous elements in the ash so that the population could be warned about the potential hazards, such as polluted drinking water. This was not at all a simple issue, as on the other hand there were scholars who realized that ash could be beneficial as a fertilizer, even as clouds of ash had obscured the sun. As chemical inquiries became more precise and the toxic concentration of many elements became known, this double life of Vesuvian ash as a scientific object gradually died.
Dyeing off: On the deaths of dyestuffs as scientific objects
Authors: Paskins Mat
Published: November 2022

Between the 1870s and the 1920s, the dye industry was at the center of claims about the productivity of organic chemistry. Dyestuffs were widely represented as the most complex molecules to find commercial application, and positioned at the center of nationalist projects to establish chemical industry, especially in Britain and the United States. By the later twentieth century, the complex of scientific hopes which surrounded dyestuffs had largely disappeared. In Hans-Jörg Rheinberger’s terms, they had changed from “epistemic things” to, at best, “technical objects,” and lost their future-bearing status as the lynchpin of organic chemistry. Although developments in dyeing continue, dyestuffs have vacated the scientifically and culturally dynamic position that they once occupied; any restoration of this status would require a radical change in economic and material conditions. This paper considers the senses in which this change of status should be considered as the death of dyestuffs as a scientific object.
Law-jobs in the algorithmic society
Authors: Fortes Pedro Rubim Borges , Restrepo Amariles David
Published: November 2022

It is now well established that algorithms are transforming our economy, institutions, social relations and ultimately our society. This paper explores the question – what is the role of law in the algorithmic society? We draw on the law-jobs theory of Karl Llewellyn and on William's Twining refinement of Llewellyn's work through the perspective of a thin functionalism to have a better understanding of what law does in this new context. We highlight the emergence of an algorithmic law, as law performs jobs such as the disposition of trouble-cases, the preventive channelling and reorientation of conduct and expectations, and the allocation of authority in the face of algorithmic systems. We conclude that the law-jobs theory remains relevant to understanding the role of law in the algorithmic society, but it is also challenged by how algorithms redefine who does or should do what law-jobs, and how they are done.
How Did I Get From There to Here?
Authors: Gordon Arnold L.
Published: November 2022

In this memoir I trace the trajectory from childhood to a career in physical oceanography. The trajectory was not based on a well thought out plan, but I had a sense of my interest in the ocean and atmosphere. One is faced with many career opportunities in life, choosing the best for you depends on your interest and talents. The better you understand them, the better you recognize “opportunity,” but be flexible, opportunity is never likely to be a perfect fit (it might actually be better fit to your “passion”). My research quest, as an observationalist, is to develop a clearer, conceptual, picture of ocean, how it “works,” with a tilt toward its role in the climate system. I have worked in the cold southern polar regions to the hot tropics, and in‐between; from the top to the bottom of the water column. Here I discuss a few discoveries that led to new insight into interocean exchange and deep ocean ventilation, which are now widely explored: Southern ocean: two modes of convection, along the margins of Antarctica and in the open ocean of the Weddell Sea; Agulhas Leakage: Indian Ocean invades the Atlantic, essential to the Atlantic Meridional Overturning Circulation; The Indonesian Throughflow: tropical Pacific water spreads into Indian Ocean, part of the global interocean thermocline exchange.
A Self‐Sustained Charge Neutrality Intracloud Lightning Parameterization Containing Channel Decay and Reactivation
Authors: Zheng Tianxue , Tan Yongbo , Wang Haichao , Shi Zheng , Lyu Weitao , Wu Bin , Zhang Yuankan
Published: November 2022

A self‐sustained charge neutrality parameterization scheme of intracloud (IC) lightning is presented in this paper. The scheme contains the following features: simultaneous development of multiple branches, polarity asymmetry of positive and negative leaders, nonlinear electrical parameters, complete charge neutrality, and channel decay and reactivation. Nonlinear electrical parameters and charge neutrality are the key factors that determinate channel decay and reactivation. To demonstrate the simulation capacity of this scheme, two simulated intracloud flashes by this scheme under the tripole charge structure are chosen for analysis. These two IC flashes show clearly the above features, where reactivation processes that initiated from different branches and the real‐time changes in nonlinear electrical parameters are mainly analyzed. The simulation results are in line with the current knowledge on lightning, which also suggests that the new scheme may become a useful tool to deeply explore the discharge phenomena involving channel decay and reactivation.
Comprehensive small RNA-sequencing of primary myeloma cells identifies miR-105-5p as a predictor of patient survival
Authors: Roseth Aass Kristin , Nedal Tonje Marie Vikene , Anshushaug Bouma Siri , Tryggestad Synne Stokke , Haukås Einar , Slørdahl Tobias Schmidt , Waage Anders , Standal Therese , Mjelle Robin
Published: November 2022

Background

Small RNAs (sRNAs), a heterogenous group of non-coding RNAs, are emerging as promising molecules for cancer patient risk stratification and as players in tumour pathogenesis. Here, we have studied microRNAs (miRNAs) and other sRNAs in relation to survival and disease severity in multiple myeloma.

Methods

We comprehensively characterised sRNA expression in multiple myeloma patients by performing sRNA-sequencing on myeloma cells isolated from bone marrow aspirates of 86 myeloma patients. The sRNA expression profiles were correlated with the patients’ clinical data to investigate associations with survival and disease subgroups, by using cox proportional hazards (coxph) -models and limma-voom, respectively. A publicly available sRNA dataset was used as external validation (n = 151).

Results

We show that multiple miRNAs are differentially expressed between ISS Stage I and III. Interestingly, we observed the downregulation of seven different U2 spliceosomal RNAs, a type of small nuclear RNAs in severe disease stages. Further, by a discovery-based approach, we identified miRNA miR-105-5p as a predictor of poor overall survival (OS) in multiple myeloma. Multivariate analysis showed that miR-105-5p predict OS independently of established disease markers.

Conclusions

Overexpression of miR-105-5p in myeloma cells correlates with reduced OS, potentially improving prognostic risk stratification in multiple myeloma.
Mitochondria and cell death-associated inflammation
Authors: Vringer Esmee , Tait Stephen W. G.
Published: November 2022

Mitochondria have recently emerged as key drivers of inflammation associated with cell death. Many of the pro-inflammatory pathways activated during cell death occur upon mitochondrial outer membrane permeabilization (MOMP), the pivotal commitment point to cell death during mitochondrial apoptosis. Permeabilised mitochondria trigger inflammation, in part, through the release of mitochondrial-derived damage-associated molecular patterns (DAMPs). Caspases, while dispensable for cell death during mitochondrial apoptosis, inhibit activation of pro-inflammatory pathways after MOMP. Some of these mitochondrial-activated inflammatory pathways can be traced back to the bacterial ancestry of mitochondria. For instance, mtDNA and bacterial DNA are highly similar thereby activating similar cell autonomous immune signalling pathways. The bacterial origin of mitochondria suggests that inflammatory pathways found in cytosol-invading bacteria may be relevant to mitochondrial-driven inflammation after MOMP. In this review, we discuss how mitochondria can initiate inflammation during cell death highlighting parallels with bacterial activation of inflammation. Moreover, we discuss the roles of mitochondrial inflammation during cell death and how these processes may potentially be harnessed therapeutically, for instance to improve cancer treatment.
Tautomycin and enzalutamide combination yields synergistic effects on castration-resistant prostate cancer
Authors: Luo Mayao , Zhang Yifan , Xu Zhuofan , Wu Chenwei , Ye Yuedian , Liu Rui , Lv Shidong , Wei Qiang
Published: November 2022

The androgen receptor (AR) plays an essential role in prostate cancer progression and is a key target for prostate cancer treatment. However, patients with prostate cancer undergoing androgen deprivation therapy eventually experience biochemical relapse, with hormone-sensitive prostate cancer progressing into castration-resistant prostate cancer (CRPC). The widespread application of secondary antiandrogens, such as enzalutamide, indicates that targeting AR remains the most efficient method for CRPC treatment. Unfortunately, neither can block AR signaling thoroughly, leading to AR reactivation within several months. Here, we report an approach for suppressing reactivated AR signaling in the CRPC stage. A combination of the protein phosphatase 1 subunit α (PP1α)-specific inhibitor tautomycin and enzalutamide synergistically inhibited cell proliferation and AR signaling in LNCaP and C4-2 cells, as well as in AR variant-positive 22RV1 cells. Our results revealed that enzalutamide competed with residual androgens in CRPC, enhancing tautomycin-mediated AR degradation. In addition, the remaining competitive inhibitory role of enzalutamide on AR facilitated tautomycin-induced AR degradation in 22RV1 cells, further decreasing ARv7 levels via a full-length AR/ARv7 interaction. Taken together, our findings suggest that the combination of tautomycin and enzalutamide could achieve a more comprehensive inhibition of AR signaling in CRPC. AR degraders combined with AR antagonists may represent a new therapeutic strategy for CRPC.
A meta-analysis of the diagnostic utility of biomarkers in cerebrospinal fluid in Parkinson’s disease
Authors: Xiang Chunchen , Cong Shengri , Tan Xiaoping , Ma Shuang , Liu Yang , Wang Hailong , Cong Shuyan
Published: November 2022

Biomarkers play important roles in the diagnosis and differential diagnosis of Parkinson’s disease (PD). Thus, we carried out a systematic review and meta-analysis evaluating the diagnostic utility of cerebrospinal fluid (CSF) biomarkers to distinguish PD from atypical parkinsonian syndromes (APSs) and controls. Data for PD and APS and controls were extracted from 123 studies that reported the concentration of CSF biomarkers. Comparisons were presented using pooled Hedges’ g. Sources of heterogeneity were evaluated using meta-regression, and subgroup and sensitivity analyses. We found that compared with controls, PD patients had lower levels of amyloid beta 1-42, phosphorylated tau, total tau, total α-synuclein, Zn, DJ-1, and YKL-40, and higher levels of oligomeric and phosphorylated α-synuclein. Moreover, lower CSF levels of neurofilament light chain, t-tau, YKL-40, and C-reactive protein were found in PD patients compared to those with multiple system atrophy. PD patients also had lower levels of NFL and higher levels of Aβ42 compared with patients with progressive supranuclear palsy. Reduced levels of p-tau and t-tau and higher Aβ42 levels were found in PD patients compared with patients with dementia with Lewy bodies. Finally, reduced NFL levels were found in patients with PD compared with patients with cortical basal degeneration. Therefore, we believe that the combinations of t-α-syn, Aβ42, and NFL could be promising biomarkers for the differential diagnosis of PD and APSs.
Deconstructing heterogeneity in schizophrenia through language: a semi-automated linguistic analysis and data-driven clustering approach
Authors: Bambini Valentina , Frau Federico , Bischetti Luca , Cuoco Federica , Bechi Margherita , Buonocore Mariachiara , Agostoni Giulia , Ferri Ilaria , Sapienza Jacopo , Martini Francesca , Spangaro Marco , Bigai Giorgia , Cocchi Federica , Cavallaro Roberto , Bosia Marta
Published: November 2022

Previous works highlighted the relevance of automated language analysis for predicting diagnosis in schizophrenia, but a deeper language-based data-driven investigation of the clinical heterogeneity through the illness course has been generally neglected. Here we used a semiautomated multidimensional linguistic analysis innovatively combined with a machine-driven clustering technique to characterize the speech of 67 individuals with schizophrenia. Clusters were then compared for psychopathological, cognitive, and functional characteristics. We identified two subgroups with distinctive linguistic profiles: one with higher fluency, lower lexical variety but greater use of psychological lexicon; the other with reduced fluency, greater lexical variety but reduced psychological lexicon. The former cluster was associated with lower symptoms and better quality of life, pointing to the existence of specific language profiles, which also show clinically meaningful differences. These findings highlight the importance of considering language disturbances in schizophrenia as multifaceted and approaching them in automated and data-driven ways.
Hippocampal representations of foraging trajectories depend upon spatial context
Authors: Jiang Wan-Chen , Xu Shengjin , Dudman Joshua T.
Published: November 2022

Animals learn trajectories to rewards in both spatial, navigational contexts and relational, non-navigational contexts. Synchronous reactivation of hippocampal activity is thought to be critical for recall and evaluation of trajectories for learning. Do hippocampal representations differentially contribute to experience-dependent learning of trajectories across spatial and relational contexts? In this study, we trained mice to navigate to a hidden target in a physical arena or manipulate a joystick to a virtual target to collect delayed rewards. In a navigational context, calcium imaging in freely moving mice revealed that synchronous CA1 reactivation was retrospective and important for evaluation of prior navigational trajectories. In a non-navigational context, reactivation was prospective and important for initiation of joystick trajectories, even in the same animals trained in both contexts. Adaptation of trajectories to a new target was well-explained by a common learning algorithm in which hippocampal activity makes dissociable contributions to reinforcement learning computations depending upon spatial context.
Causal analysis and visualization of magnetization reversal using feature extended landau free energy
Authors: Kunii Sotaro , Masuzawa Ken , Fogiatto Alexandre Lira , Mitsumata Chiharu , Kotsugi Masato
Published: November 2022

The magnetization reversal in nanomagnets is causally analyzed using an extended Landau free-energy model. This model draws an energy landscape in the information space using physics-based features. Thus, the origin of the magnetic effect in macroscopic pinning phenomena can be identified. The microscopic magnetic domain beyond the hierarchy can be explained using energy gradient analysis and its decomposition. Structural features from the magnetic domains are extracted using persistent homology. Extended energy is visualized using ridge regression, principal component analysis, and Hadamard products. We found that the demagnetization energy concentration near a defect causes the demagnetization effect, which quantitatively dominates the pinning phenomenon. The exchange energy inhibits pinning, promotes saturation, and shows slight interactions with the defect. Furthermore, the energy distributions are visualized in real space. Left-position defects reduce the energy barrier and are useful for the topological inverse design of recording devices.
Modelling the propagation of infectious disease via transportation networks
Authors: Anupriya  , Bansal Prateek , Graham Daniel J.
Published: November 2022

The dynamics of human mobility have been known to play a critical role in the spread of infectious diseases like COVID-19. In this paper, we present a simple compact way to model the transmission of infectious disease through transportation networks using widely available aggregate mobility data in the form of a zone-level origin-destination (OD) travel flow matrix. A key feature of our model is that it not only captures the propagation of infection via direct connections between zones (first-order effects) as in most existing studies but also transmission effects that are due to subsequent interactions in the remainder of the system (higher-order effects). We demonstrate the importance of capturing higher-order effects in a simulation study. We then apply our model to study the first wave of COVID-19 infections in (i) Italy, and, (ii) the New York Tri-State area. We use daily data on mobility between Italian provinces (province-level OD data) and between Tri-State Area counties (county-level OD data), and daily reported caseloads at the same geographical levels. Our empirical results indicate substantial predictive power, particularly during the early stages of the outbreak. Our model forecasts at least 85% of the spatial variation in observed weekly COVID-19 cases. Most importantly, our model delivers crucial metrics to identify target areas for intervention.
Bone marrow-derived vasculogenesis leads to scarless regeneration in deep wounds with periosteal defects
Authors: Shirai Yuuki , Okano Junko , Nakagawa Takahiko , Katagi Miwako , Nakae Yuki , Arakawa Atsuhiro , Koshinuma Shinya , Yamamoto Gaku , Kojima Hideto
Published: November 2022

Deep skin wounds with periosteal defects, frequently caused by traffic accidents or radical dissection, are refractory. Transplant surgery is frequently performed, but patients are subjected to stress for long operation periods, the sacrifice of donor regions, or several complications, such as flap necrosis or intractable ulcers. Even if the defects are covered, a scar composed of fibrous tissue remains in the body, which can cause itching, dysesthesia, or repeated ulcers because of the lack of distribution of peripheral nerves or hair follicles. Thus, treatments with the aim of regenerating lost tissue for deep wounds with periosteal defects are needed. Here, we show that the use of gelatin sponges (GS), which have been used as haemostatic materials in clinical practice, allowed the regeneration of heterogeneous tissues, including periosteum, skin, and skin appendages, when used as scaffolds in deep wounds with periosteal defects in rats. Bone marrow transplantation in rats revealed the mechanism by which the microenvironment provided by GS enabled bone marrow-derived cells (BMDCs) to form a vascular niche, followed by regeneration of the periosteum, skin, or skin appendages such as hair follicles by local cells. Our findings demonstrated that vascular niche formation provided by BMDCs is crucial for heterogeneous tissue regeneration.
Obstructive sleep apnea in young Asian adults with sleep-related complaints
Authors: Chiu Hwa-Yen , Chou Kun-Ta , Su Kang-Cheng , Lin Fang-Chi , Liu Yung-Yang , Shiao Tsu-Hui , Chen Yuh-Min
Published: November 2022

This study aimed to investigate the proportion of young OSA adults with sleep-related complaints in a sleep center, affiliated with a tertiary medical center for over a decade. This study presents a chronicle change in the numbers of young adults receiving polysomnography (PSG) and young patients with OSA from 2000 to 2017. We further analyzed 371 young patients with OSA among 2378 patients receiving PSG in our sleep center from 2016 to 2017 to capture their characteristics. Young adults constituted a substantial and relatively steady portion of examinees of PSG (25.1% ± 2.8%) and confirmed OSA cases (19.8 ± 2.4%) even though the total numbers increased with the years. Young adults with OSA tend to be sleepier, have a greater body mass index, and have a higher percentage of cigarette smoking and alcohol consumption. They also complained more about snoring and daytime sleepiness. They had a higher apnea–hypopnea index on average and experienced more hypoxemia during their sleep, both in terms of duration and the extent of desaturation. Even though the prevalence of comorbidities increased with age, hypertension in young male adults carried higher risks for OSA. Young adults with OSA have constituted a relatively constant portion of all confirmed OSA cases across time. The young adults with OSA were heavier, more symptomatic, and with more severe severity.

Clinical trial: The Institutional Review Board of Taipei Veterans General Hospital approved the study (VGHIRB No. 2018-10-002CC). The study is registered with ClinicalTrials.gov, number NCT03885440.